PMID- 8130487
TI  - The Automatic Patient Symptom Monitor (APSM): a voice mail system for clinical
      research.
AB  - Double-blind clinical trials become very tedious when symptoms are measured
      rather than objective laboratory and physical parameters. The standard "diary
      card" method is labor intensive for patients and impractical to use for more than
      a few weeks. In chronic relapsing disorders it would be far better for patients
      to record symptoms one or more times per day, at defined times, for weeks, months
      or even years. The Automatic Patient Symptom Monitor (APSM) is a voice processing
      system designed to achieve this goal. APSM calls patients at home every night,
      addresses each patient by name and then asks a set of questions which patients
      answer by pressing the touch tone keys on their telephone. APSM enters data into
      a computer database file which can be easily retrieved by investigators, even by
      modem. In a pilot study, patients with telephones easily learned how to use APSM.
      They were given therapy for a gastric infection (H.pylori) and were monitored by
      APSM until follow-up one month after completing treatment. Eight of nine patients
      recorded valid data on > 80% of study days. In all cases, APSM data matched the
      patient's own impression of whether they were better, the same, or worse. With
      one exception, APSM assessment correlated with microbiologic data obtained post
      therapy i.e. when the gastric infection had been eradicated, patients felt better
      (p < 0.047). Long term clinical monitoring with APSM may decrease clinical trial
      time and improve the statistical power of double blind studies.

PMID- 8130488
TI  - A pen-based system to support pre-operative data collection within an anaesthesia
      department.
AB  - This paper describes the design and implementation of a pen-based computer system
      for remote preoperative data collection. The system is envisaged to be used by
      anaesthesia staff at different hospital scenarios where pre-operative data are
      generated. Pen-based technology offers important advantages in terms of
      portability and human-computer interaction, as direct manipulation interfaces by
      direct pointing, and "notebook user interfaces metaphors". Being the human
      factors analysis and user interface design a vital stage to achieve the
      appropriate user acceptability, a methodology that integrates the "usability"
      evaluation from the earlier development stages was used. Additionally, the
      selection of a pen-based computer system as a portable device to be used by
      health care personnel allows to evaluate the appropriateness of this new
      technology for remote data collection within the hospital environment. The work
      presented is currently being realised under the Research Project "TANIT:
      Telematics in Anaesthesia and Intensive Care", within the "A.I.M.--Telematics in
      Health CARE" European Research Program.

PMID- 8130489
TI  - The patient problem/nursing diagnosis form: a computer-generated chart document.
AB  - The INFORMM (Information Network for Online Retrieval & Medical Management)
      patient problem/nursing diagnosis form is a computer-generated, patient record
      document of information related to identified patient conditions and patient
      outcomes. These patient and nursing data, accessible online as well as in paper
      copy, enhance continuity of care by providing, to all authorized clinicians, a
      list and history of identified patient problems/nursing diagnoses and the
      patient's status in terms of the achievement of projected patient outcomes. This
      cumulative, patient-centered documentation facilitates patient care effectiveness
      and provides mechanisms to capture and retrieve patient and outcome data for
      quality improvement and research purposes.

PMID- 8130490
TI  - An X Window system for statlab results reporting.
AB  - We have developed a system that receives "stat" results encoded in Health Level
      Seven from the Laboratory Information System, prints a report in destination
      Intensive Care Units (ICUs), and captures the data for review in a custom
      spreadsheet format at color X-terminals located in ICUs. Available services
      include a reference nomogram plot of arterial blood gas data, printed summaries,
      automated access to the Clinical Information System and a Medline database,
      electronic mail, a simulated electronic calculator, and general news and
      information. Security mechanisms include an audit trail of user activities on the
      system. Noteworthy technical aspects and non-technical factors impacting success
      are discussed.

PMID- 8130491
TI  - Clinical performance of a rule-based decision support system for mechanical
      ventilation of ARDS patients.
AB  - We developed a clinical decision support system--ventilation protocols--that
      managed tidal volume and ventilator rate settings during mechanical ventilation
      of patients with the Adult Respiratory Distress Syndrome (ARDS). We applied these
      protocols for a total of 10,903 hours in 40 ARDS patients. The clinical staff
      suspended the protocols for only 5% of the total application time due to medical
      procedures, surgeries, transient clinical problems not addressed by the
      protocols, or because of attending physician request. Of 3,148 instructions
      generated by the ventilation protocols, the clinical staff followed 2,932 (93%).
      The staff did not follow some instructions because of patient data errors,
      computer software and protocol logic errors, inability of the clinical staff to
      implement protocol instructions because of more pressing duties, and clinical
      staff objections to specific instructions. Sixty percent of the patients treated
      by the ventilation protocols survived. Our results demonstrate that the
      ventilation protocols provided a practical and safe decision support system for
      the mechanical ventilation of ARDS patients.

PMID- 8130492
TI  - Dynamic selection of models for a ventilator-management advisor.
AB  - A ventilator-management advisor (VMA) is a computer program that monitors
      patients who are treated with a mechanical ventilator. A VMA implements a patient
      specific physiologic model to interpret patient data and to predict the effects
      of alternative control settings for the ventilator. Because a VMA evaluates its
      physiologic model repeatedly during each cycle of data interpretation, highly
      complex models may require more computation time than is available in this time
      critical application. On the other hand, less complex models may be inaccurate if
      they are unable to represent a patient's physiologic abnormalities. For each
      patient, a VMA should select a model that balances the tradeoff of prediction
      accuracy and computation-time complexity. I present a method to select models
      that are at an appropriate level of detail for time-constrained decision tasks.
      The method is based on a local search in a graph of models (GoM) for a model that
      maximizes the tradeoff of computation-time complexity and prediction accuracy.
      For each model under consideration, a belief network computes a probability of
      model adequacy given the qualitative prior information, and the goodness of fit
      of the model to the data provides a measure of the conditional probability of
      adequacy given the quantitative observations. I apply this method to the problem
      of model selection for a VMA. I describe an implementation of a graph of
      physiologic models that range in complexity from VentPlan, a simple model with 3
      compartments, to VentSim, a multicompartment model with detailed airway,
      circulation and mechanical ventilator components.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8130493
TI  - Providing clinicians with problem-based access to knowledge: troubleshooting
      pulmonary artery catheter waveforms.
AB  - This paper describes a microcomputer system for providing computer-based access
      to expert knowledge in the area of troubleshooting pulmonary artery (PA) catheter
      waveforms. The system is used by both nurses and physicians in an 18-bed medical
      intensive care unit. Its dominant features are 1) problem-focused access to
      knowledge, and 2) heavy use of graphics and images to explicate knowledge. The
      system is used by both nurses and physicians in an 18-bed medical intensive care
      unit. An evaluation protocol is in place to examine the impact of the system on
      clinicians' knowledge, their decision-making skills, their satisfaction with the
      system, and costs of orientation related to PA waveform troubleshooting.

PMID- 8130494
TI  - Computerized detection of arterial oxygen desaturations in an intensive care
      unit.
AB  - Automatic detection of arterial oxygen desaturations was investigated by
      collecting pulse oximeter saturation data through an MIB. Two algorithms, one
      based on a threshold principle and the other based on moving median calculations,
      performed the detection. The median algorithm detected fewer "unimportant" events
      than did the threshold algorithm, but also did not detect some "important" events
      that the threshold algorithm detected. Successful detection algorithms will
      likely need to incorporate into their decision-making other patient information
      in addition to saturation. A proposed recording algorithm is described.

PMID- 8130495
TI  - Modeling mortality in the intensive care unit: comparing the performance of a
      back-propagation, associative-learning neural network with multivariate logistic
      regression.
AB  - The objective of this study was to compare and contrast two techniques of
      modeling mortality in a 30 bed multi-disciplinary ICU; neural networks and
      logistic regression. Fifteen physiological variables were recorded on day 3 for
      422 consecutive patients whose duration of stay was over 72 hours. Two separate
      models were built using each technique. First, logistic and neural network models
      were constructed on the complete 422 patient dataset and discrimination was
      compared. Second, the database was randomly divided into a 284 patient
      developmental dataset and a 138 patient validation dataset. The developmental
      dataset was used to construct logistic and neural net models and the predictive
      power of these models was verified on the validation dataset. On the complete
      dataset, the neural network clearly outperformed the logistic model (sensitivity
      and specificity of 1 and .997 vs. .525 and .966, area under ROC curve .9993 vs.
      .9259), while both performed equally well on the validation dataset (area under
      ROC of .82). The excellent performance of the neural net on the complete dataset
      reveals that the problem is classifiable. Since our dataset only contained 40
      mortality events, it is highly likely that the validation dataset was not
      representative of the developmental dataset, which led to a decreased predictive
      performance by both the neural net and the logistic regression models.
      Theoretically, given an extensive dataset, the neural network should be able to
      perform mortality prediction with a sensitivity and a specificity approaching
      95%. Clinically, this would be an extremely important achievement.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8130496
TI  - Non-invasive assessment of cardiovascular mechanics using a new, user-friendly
      software application.
AB  - Currently, in most non-invasive imaging laboratories, echocardiographic tracings
      are interpreted by "eyeballing" M-mode and 2-dimensional echocardiographic
      recordings. This subjective method of data analysis severely hampers the
      possibility of serial assessment of physiological interventions on cardiovascular
      disease states. Moreover, acquisition of important cardiovascular physiological
      data usually requires recordings of instantaneous aortic pressure and flow data
      that, until recently, could only be acquired invasively in the cardiac
      catheterization laboratory. Recently, our laboratory has developed and validated
      new "non-invasive" methods for the acquisition of aortic pressure and flow using
      calibrated subclavian pulse tracings and continuous wave aortic Doppler,
      respectively. With these limitations and new developments in mind, we developed
      new software that enables simultaneous non-invasive acquisition of left
      ventricular (LV) chamber geometry and aortic pressure and flow data. This new,
      user-friendly software in conjunction with other non-invasive tools allows non
      invasive quantification of multiple cardiovascular physiological parameters. More
      importantly, the new software enables objective and serial assessment of multiple
      pharmacological interventions on various patients' disease states.

PMID- 8130497
TI  - Computerized, telephone-based stress management program.
AB  - A stress management program that used computerized, telephone-based technology
      was offered to the public via a free, "800" telephone number. The program was
      intended to reach a very large number of persons, while requiring a minimum of
      staff time. The program used an interactive telephone system, employing natural
      sounding, digitized voice, and touch tone recognition of callers' responses. The
      program was available 24 hours a day. It composed each message to suit the
      individual needs and expectations of each caller. A controlled evaluation of the
      program was conducted to determine how the messages could be worded and presented
      most effectively. The results suggest that subjects were most likely to find the
      messages in the program helpful, to carry out the stress management instructions,
      and to continue calling when the messages were personalized and contained
      homework assignments.

PMID- 8130498
TI  - Graphical electrocardiogram waveforms as part of an integrated hospital system's
      patient record.
AB  - The U.S. Department of Veterans Affairs (VA) has an ongoing project to integrate
      diagnostic images into its existing text-based hospital information system. High
      quality images from cardiology, pulmonary medicine, gastroenterology, endoscopy,
      pathology, radiology, hematology and nuclear medicine can be displayed for
      clinicians quickly and conveniently on workstations throughout the hospital. As a
      part of this endeavor, diagnostic-quality computer generated 12-lead
      electrocardiograms, including both median and rhythm data, can be viewed as a
      part of the on-line patient record of an integrated hospital information system.
      Now computer generated graphics can be included in the longitudinal patient
      record. Incorporating generated graphics and images into a text based patient
      record is another step towards the next generation of integrated hospital
      information system with multimedia patient records.

PMID- 8130499
TI  - Uses of diagnostic expert systems in clinical care.
AB  - The development and testing of computerized systems to assist in the diagnostic
      process is a time honored research activity in medical information science. The
      focus of the majority of the applications produced is on providing accurate
      diagnostic suggestions when appropriate clinical information is entered. We
      believe that diagnostic knowledge has a much wider range of uses than that of
      simply assigning diagnostic labels. Below we describe three applications which
      illustrate alternate uses for diagnostic systems. Applications that assist in
      data collection, assess the quality of medical reports, and extract relevant
      clinical data from natural language x-ray reports are discussed. We believe that
      more effort should be directed toward studying the use of diagnostic knowledge
      bases in processes that help plan diagnostic strategies, in quality assurance
      applications, and in processes that facilitate all aspects of medical
      communication.

PMID- 8130500
TI  - Epileptologist's assistant: a cost effective expert system.
AB  - Epileptologist's Assistant is an expert system designed to cost effectively
      handle routine care in an epilepsy follow up clinic. The system guides nurses in
      gathering patient histories and then generates progress notes and a patient
      information sheet. The progress note, organized in the SOAP format, is reviewed
      by the physician with the patient. For difficult cases the physician may modify
      the Assessment or Plan sections; the Subjective and Objective sections rarely
      need modifications. The assertion of cost-effectiveness is based on time/motion
      data. Without the system a physician in our epilepsy clinic spends about 21
      minutes seeing a patient. With the system the nurse spends about 14 minutes with
      the patient and the physician spends about 7 minutes. Two nurses and a physician
      handle the work load of 3 physicians. Physician time is cut by about 66%. Using
      the average salaries for physicians and nurses at the Department of Veterans
      Affairs, the cost of a clinic visit is reduced 39% by using the expert system and
      nurses. In addition, the progress note is more legible, it contains more
      information, Q/A procedures are implemented at the point of patient contact, and
      the data is entered into a computer system in a data field format.

PMID- 8130501
TI  - Data explorer: a prototype expert system for statistical analysis.
AB  - The inadequate analysis of medical research data, due mainly to the
      unavailability of local statistical expertise, seriously jeopardizes the quality
      of new medical knowledge. Data Explorer is a prototype Expert System that builds
      on the versatility and power of existing statistical software, to provide
      automatic analyses and interpretation of medical data. The system draws much of
      its power by using belief network methods in place of more traditional, but
      difficult to automate, classical multivariate statistical techniques. Data
      Explorer identifies statistically significant relationships among variables, and
      using power-size analysis, belief network inference/learning and various
      explanatory techniques helps the user understand the importance of the findings.
      Finally the system can be used as a tool for the automatic development of
      predictive/diagnostic models from patient databases.

PMID- 8130502
TI  - Integrating decision support, based on the Arden Syntax, in a clinical laboratory
      environment.
AB  - A clinical decision support system prototype have been developed in the clinical
      laboratory environment. The knowledge base consists of Medical Logic Modules,
      written in the Arden Syntax, and the work describes how these modules can be
      written, evoked and executed in a system, that is integrated with a laboratory
      information system, and facilitate real time validation of laboratory data. Tools
      and methods for building a decision support system are described and design
      aspects, such as database access, system validation and platform independence,
      are discussed.

PMID- 8130503
TI  - Sharing MLM's: an experiment between Columbia-Presbyterian and LDS Hospital.
AB  - The use of Arden syntax for development of shareable medical logic modules
      (MLM's) has developed as an ASTM standard. To test the feasibility of sharing
      MLM's between institutions a study was conducted between Columbia-Presbyterian
      Medical Center and LDS Hospital. In this study seven MLM's clinically executing
      at Columbia-Presbyterian were used to test the sharing potential of the Arden
      syntax. The study was limited to measuring the modifications necessary to make
      executable at LDS Hospital the shared MLM's. Because of the site specific nature
      of the data variables, multiple modifications were required. Three classes of
      modifications were necessary. The simplest involved only data variable mappings.
      The other classes required either minor modifications to the logic or relatively
      major modifications. Over 50% of the modifications were in the minor or major
      classes. While the sharing of decision logic was possible and facilitated by the
      use of the MLM's at the two sites, the absence of standard medical vocabularies
      limited the utility of the MLM as a mechanism for directly sharing medical
      knowledge.

PMID- 8130504
TI  - Integrality and meaning: essential and orthogonal dimensions of graphical data
      display.
AB  - There are few sound principles, rules, or laws to guide construction of graphic
      displays of medical data or information. The present paper describes two
      orthogonal dimensions of data displays: integrality and meaningfulness. These are
      hypothesized to be both fundamental building blocks of a theory of graphic
      representation and programmatically useful principles for organizing previously
      created graphic displays and creating new ones. Examples taken from recent
      medical informatics literature illustrate high and low integral vs. high and low
      meaningful displays. If the present analysis is correct, then pattern recognition
      tasks will be better supported by displays that are high on both integrality and
      meaningfulness. Integrality, it is hypothesized, increased the degree to which a
      pattern is apparent. Meaningfulness increases the degree to which a pattern, once
      detected, is interpretable.

PMID- 8130505
TI  - Recognizing new medical knowledge computationally.
AB  - Can new medical knowledge be recognized computationally? We know knowledge is
      changing, and our knowledge-based systems will need to accommodate that change in
      knowledge on a regular basis if they are to stay successful. Computational
      recognition of these changes seems desirable. It is unlikely that low level
      objects in the computational universe, bits and characters, will change much over
      time, higher level objects of language, where meaning begins to emerge, may show
      change. An analysis of ten arbitrarily selected paragraphs from the Medical
      Knowledge Self-Assessment Program of the American College of Physicians was used
      as a test bed for nominal phrase recognition. While there were words not known to
      Meta-1.2, only 8 of the 32 concepts new to the primary author were pointed to by
      new words. Use of a barrier word method was successful in identifying 23 of the
      32 new concepts. Use of co-occurrence (in sentences) of putative nominal phrases
      may reduce the amount of human effort involved in recognizing the emergence of
      new relationships.

PMID- 8130506
TI  - Improving the efficiency of patient recruitment with an automated telephone
      screening system in a client-server environment.
AB  - An automated telephone screening system was implemented at the Baltimore VA
      Hospital on a Local Area Network (LAN) to evaluate older adults for the GRECC
      research program. Using the system for decision support, a registered nurse (RN)
      placed 117 phone calls to older adults in the Baltimore community over a 3 month
      period. The modular design of the system allowed tracking of inclusion and
      exclusion criteria which was shared by clinicians and researchers. The design
      goal of the telephone screening system was to reduce time and personnel costs and
      increase the effectiveness of screening for recruitment for a major research
      project. Effectiveness is defined as avoiding under--or over--screening. Using
      the telephone system, it is estimated the research team saved over $6,000.00 in
      unnecessary medical evaluation in a 3 months period. As the system develops, the
      process by which older adults are assessed for research programs in the
      Geriatrics Service at the Baltimore VAMC will provide additional cost
      efficiencies.

PMID- 8130507
TI  - Goals for concept representation in the GALEN project.
AB  - The GALEN project aims to develop language independent concept representation
      systems as the foundations for the next generation of multilingual coding
      systems. Traditional coding schemes have reached the limits of what can be
      maintained and managed, and a shift to formal compositional systems is now
      essential. GALEN is developing one such scheme and an associated concept model,
      together with criteria for their evaluation. It should provide the flexibility
      required to cope with the diversity amongst medical applications, whilst ensuring
      the coherence necessary for integration and re-use of terminologies.

PMID- 8130508
TI  - An intelligent interactive simulator of clinical reasoning in general surgery.
AB  - We introduce an interactive computer environment for teaching in general surgery
      and for diagnostic assistance. The environment consists of a knowledge-based
      system coupled with an intelligent interface that allows users to acquire
      conceptual knowledge and clinical reasoning techniques. Knowledge is represented
      internally within a probabilistic framework and externally through a interface
      inspired by Concept Graphics. Given a set of symptoms, the internal knowledge
      framework computes the most probable set of diseases as well as best
      alternatives. The interface displays CGs illustrating the results and prompting
      essential facts of a medical situation or a process. The system is then ready to
      receive additional information or to suggest further investigation. Based on the
      new information, the system will narrow the solutions with increased belief
      coefficients.

PMID- 8130509
TI  - Automated modeling of medical decisions.
AB  - We have developed a graph grammar and a graph-grammar derivation system that,
      together, generate decision-theoretic models from unordered lists of medical
      terms. The medical terms represent considerations in a dilemma that confronts the
      patient and the health-care provider. Our current grammar ensures that several
      desirable structural properties are maintained in all derived decision models.

PMID- 8130510
TI  - AIDS2: a decision-support tool for decreasing physicians' uncertainty regarding
      patient eligibility for HIV treatment protocols.
AB  - We have developed a decision-support tool, the AIDS Intervention Decision-Support
      System (AIDS2), to assist in the task of matching patients to therapy-related
      research protocols. The purposes of AIDS2 are to determine the initial
      eligibility status of HIV-infected patients for therapy-related research
      protocols, and to suggest additional data-gathering activities that will decrease
      uncertainty related to the eligibility status. AIDS2 operates in either a patient
      driven or protocol-driven mode. We represent the system knowledge in three
      combined levels: a classification level, where deterministic knowledge is
      represented; a belief-network level, where probabilistic knowledge is
      represented; and a control level, where knowledge about the system's operation is
      stored. To determine whether the design specifications were met, we presented a
      series of 10 clinical cases based on actual patients to the system. AIDS2
      provided meaningful advice in all cases.

PMID- 8130511
TI  - Application of artificial neural networks for reduction of false-positive
      detections in digital chest radiographs.
AB  - A methodology based on the fuzzy set theory and the convolution neural network
      (CNN) architecture is proposed to tackle the problem of reducing false-positive
      rate in automatic lung nodule detection. The CNN which simulates human visual
      mechanism was trained by a supervised back-propagation algorithm based on fuzzy
      membership functions. The training and testing database consists of image blocks
      (each 32 x 32 pixels) of suspected lung nodule areas (nodule candidates) which
      were generated from our pre-scanning program [1]. A linguistic label was assigned
      to each nodule candidate of the training set, then the label was converted to a
      membership value through a pre-defined membership function and used as teaching
      signal (desired outputs) during the network learning. Before the nodule candidate
      was fed to the network input, it was pre-processed to reduce the complex
      background noise and the contrast discrepancy resulted from film development.
      During the network testing phase, a defuzzification process was applied to
      decipher the trained network's output triggered by the nodule candidate in the
      testing set. Finally, a Receiver Operating Characteristic (ROC) analysis was used
      to evaluate the CNN's performance based on the defuzzified output of the testing
      database. Preliminary results showed an average Az (the performance index) of
      0.84 which is equivalent to 0.80 true-positive detection (sensitivity) with an
      average 2-3 false-positive detections per chest image.

PMID- 8130512
TI  - A decision aid for diagnosis of liver lesions on MRI.
AB  - Abdominal magnetic resonance imaging (MRI) plays an important role in the
      evaluation of liver abnormalities. The interpretation of MR images requires
      expert training in a rapidly changing field. DAFODILL (Decision Aid for
      Diagnosing Liver Lesions) is a decision-support tool designed to aid radiologists
      in the diagnosis of hepatic lesions seen on MRI. DAFODILL uses a knowledge base
      of MRI findings and a belief-network inference engine to generate probabilistic
      differential diagnoses of the most commonly encountered hepatic lesions. DAFODILL
      performs limited image processing to identify clinically relevant features, which
      are presented to the user for confirmation before they are used by the network.
      Preliminary evaluation of an initial version of the system suggests that DAFODILL
      may be a useful tool for radiology residents and nonexpert radiologists in
      interpreting MR images of the liver.

PMID- 8130513
TI  - Hypothesis-driven data abstraction with trend templates.
AB  - We have written a prototype computer program called TrenDx for automated trend
      detection during process monitoring. The program uses a representation called
      trend templates that define disorders as typical patterns of relevant variables.
      These patterns guide the assignment of primary data to abstracted intervals or
      phases of the monitored process. TrenDx has been applied to the task of pediatric
      growth monitoring. The results of an exploratory clinical trial are reviewed
      here. The general utility of TrenDx for clinical trend detection and diagnosis is
      illustrated with examples from several task domains.

PMID- 8130514
TI  - Knowledge reuse: temporal-abstraction mechanisms for the assessment of children's
      growth.
AB  - Currently, many workers in the field of medical informatics realize the
      importance of knowledge reuse. The PROTEGE-II project seeks to develop and
      implement a domain-independent framework that allows system builders to create
      custom-tailored role-limiting methods from generic reusable components. These new
      role-limiting methods are used to create domain- and task-specific knowledge
      acquisition tools with which an application expert can generate domain- and task
      specific decision-support systems. One required set of reusable components
      embodies the problem-solving knowledge to generate temporal abstractions.
      Previously, members of the PROTEGE-II project have used these temporal
      abstraction mechanisms to infer the presence of myelotoxicity in patients with
      AIDS. In this paper, we show that these mechanisms are reusable in the domain of
      assessment of children's growth.

PMID- 8130515
TI  - A hybrid system for diagnosing multiple disorders.
AB  - This paper investigates the advantages of introducing feedback between the
      processes of automated medical diagnosis and automated diagnostic-knowledge
      acquisition. Experimental results show that a diagnostic system with such
      feedback is capable of an efficiency/accuracy trade-off when applied to the
      problem of diagnosing multiple disorders. A primary feature of this work is a new
      mechanism, called the "diagnostic-unit" representation, for remembering results
      of previous diagnoses. The diagnostic-unit representation is explicitly tailored
      to capture the most likely relationships between disorders and clusters of
      findings. Unlike typical bipartite "If-Then" representations, the diagnostic-unit
      representation uses a general graph representation to efficiently represent
      complex causal relationships between disorders and clusters of findings. In
      addition to the basic diagnostic-unit concept, this paper presents experience
      based strategies for incrementally deriving and updating diagnostic units and the
      various relationships between them. Techniques for selecting diagnostic units
      relevant to a given problem and then combining them to generate solutions are
      also described.

PMID- 8130516
TI  - HYCONES: a hybrid connectionist expert system.
AB  - This paper describes HYCONES, a tightly-coupled Hybrid Connectionist Expert
      System that integrates neural networks with a symbolic approach (frames). The
      symbolic paradigm provides rich and flexible constructs to describe the domain
      knowledge, while the connectionist one provides the system with learning
      capabilities. The paper describes the architecture of the system, focusing on the
      hybrid aspects of the knowledge base and on its automatic knowledge acquisition
      technique from a case database. The first validation of the system is presented.
      At the end, a comparison with related research efforts and future developments
      are discussed.

PMID- 8130517
TI  - Formal representation of a conceptual data model for the patient-based medical
      record.
AB  - We present a general architecture for the patient-based medical record as it is
      being developed for the SAMS, a private social security system. The conceptual
      data model is described in a convenient formal notation, the entity-relationship
      diagram. Although following the original formulation of the problem-oriented
      medical record (POMR), the data model was designed with a level of generalization
      that, functionally, makes structural differences between conventional and POMR no
      longer apparent. The main features of this model are its adaptability to
      individual work practices and its problem-oriented structure, including the
      representation of problems' evolution. This structure will enable physicians to
      organize the data, mostly collected elsewhere, by explicitly relating the facts
      that constitute a particular patient record, which is a simple way to store
      context information and clinical knowledge that is not part of patient data.

PMID- 8130518
TI  - Evaluating the quality of a probabilistic diagnostic system using different
      inferencing strategies.
AB  - In this paper we describe the evaluation of a probabilistic diagnostic system for
      patients with renal mass. Three inference models: Multi-membership Bayesian (MB),
      Minimal Diagnosis (MD) and Bayesian Network (BN), and 72 patients are used to
      illustrate three interrelated measures of system performance: accuracy,
      reliability and discriminating power. The inferencing strategies we tested
      demonstrated the kind of trade-offs in the performance measures that can be
      expected from imperfect systems. Ultimately, the purpose and expected use of a
      system should dictate the relative importance ascribed to different aspects of
      system performance.

PMID- 8130519
TI  - Dynamic decision modeling in medicine: a critique of existing formalisms.
AB  - Dynamic decision models are frameworks for modeling and solving decision problems
      that take into explicit account the effects of time. These formalisms are based
      on structural and semantical extensions of conventional decision models, e.g.,
      decision trees and influence diagrams, with the mathematical definitions of
      finite-state semi-Markov processes. This paper identifies the common theoretical
      basis of existing dynamic decision modeling formalisms, and compares and
      contrasts their applicability and efficiency. It also argues that a subclass of
      such dynamic decision problems can be formulated and solved more effectively with
      non-graphical techniques. Some insights gained from this exercise on automating
      the dynamic decision making process are summarized.

PMID- 8130520
TI  - An evaluation of factors influencing Bayesian learning systems.
AB  - This paper examines the influences of situational and model factors upon the
      accuracy of Bayesian learning systems. In particular, it is concerned with the
      impact of variations in training sample size, number of attributes, choice of
      Bayesian model, and criteria for excluding model attributes upon the overall
      accuracy of the simple and proper Bayes models.

PMID- 8130521
TI  - The Universal Patient Identifier: a discussion and proposal.
AB  - The broad-based need for a standard, robust patient identifier is reviewed.
      Advantages and difficulties of the Social Security Number are considered. An
      alternative number, composed of birthdate, location, and check digits, is
      proposed. Logistic extensions of the geographically based schema are made for
      provider and facility identification. Several variations of representation are
      described in base 34, which make the composite number short, easily derived and
      decoded, and robust.

PMID- 8130522
TI  - Probabilistic constraint satisfaction with structural models: application to
      organ modeling by radial contours.
AB  - One of the key challenges within medical information sciences is the development
      of useful models for biological structure and its variability. Many biomedical
      problems involve the elucidation of structure (for example, from experimental
      data or from imaging studies), and structural models can often drive the process
      of inferring precise structure from data. Ideally, model-driven data
      interpretation combines knowledge about the generic features of a class of
      biological structures (as contained within a model) with data that provide
      specific information (often noisy) about a particular instance of the class. In
      this paper we briefly discuss model-driven determination of biological structure
      as an example of a structural constraint satisfaction problem. We describe a
      probabilistic implementation of structural constraint satisfaction, and show that
      our formulation of a particular organ modeling technology (Radial Contour Models)
      exhibits promising performance. Our results demonstrate the utility of
      probabilistic models for the solution of structural constraint satisfaction
      problems.

PMID- 8130523
TI  - A network model for wide area access to structural information.
AB  - Structural information in medicine is information about the physical body. Recent
      advances in medical imaging and biotechnology have greatly increased the amount
      and importance of structural information, and advances in networking envisioned
      by the High Performance Computing and Communication Initiative (HPCC) will allow
      this kind of information to be delivered to remote clients over wide area
      networks. One of the most important factors determining the usability of such a
      client-server configuration is the time delay between the request for information
      from the server, and its presentation to the user at the client. In this paper we
      present a model for predicting the performance of a structural information client
      based on the ping time, a simple, unobtrusive network measurement. Preliminary
      results suggest that the relationship between ping time and transfer time for
      large files is linear, which if borne out by more data, will allow the
      performance of structural information clients at remote sites to be predicted
      without the expense of installing them first. At the same time, such a model will
      be useful for planning improvements to the network in those sites which could
      most benefit by wide area access to structural information.

PMID- 8130524
TI  - An object model for uniform access to heterogeneous databases.
AB  - The vast amount of patient information collected and maintained by hospitals is
      seldom stored in a single database. Much programming effort is wasted on
      formulating specific queries for each of several data sources, rather than
      focusing attention on developing the intended functionality of the application.
      This problem becomes more apparent as more data sources become available. The
      most obvious strategy for dealing with this multiplicity of data sources, namely
      storing all data in a single database, is impractical for reasons such as
      security and administrative control. This paper describes one possible solution
      to managing access to several database systems within applications. Using object
      oriented techniques, the solution identifies the commonality among database
      management systems and provides a uniform method of communication between
      applications and databases. We describe a C(++)-based implementation which
      embodies these concepts.

PMID- 8130525
TI  - An object-based approach to medical process automation.
AB  - The medical events of providers rendering services for patient care are
      necessarily interrelated. A clinical information system must reliably record
      these events and relate the information about their inter-dependency. The quality
      of clinical information therefore depends crucially on the proper coordination
      and tracking of these events according to established protocols. We introduce an
      object-based approach to define medical processes for their automation. For each
      medical process, we capture in one logical unit, an event-driven mechanism to
      coordinate of inter-dependent medical events of the process, and the data
      relevant to the process. We call the encapsulated unit a form object. Moreover,
      the form object may contain sub-objects each of which also encapsulates its own
      protocol knowledge and relevant information. In contrast to other approaches, the
      form object facilitates for administering medical processes due to its locality
      of definition, and its event-driven paradigm reflects medical events more
      naturally.

PMID- 8130526
TI  - Decision-theoretic information pretrieval: a generalization of reminding.
AB  - Reminder systems and clinical medical librarian services often provide
      information to clinicians without requiring that a clinician actively seek
      information. This characteristic may explain in part the effectiveness and high
      clinician acceptance of these systems. We term systems with this characteristic
      "information pretrieval systems" to distinguish them from information retrieval
      systems, which require a clinician to articulate an information need in the form
      of a query. Because of the increasing importance of information pretrieval
      systems in medical care, we have developed a decision-theoretic model of an ideal
      information pretrieval system. In this paper, we present this model and suggest
      its use as an analytic framework for understanding existing approaches, and as a
      formal basis for a functioning pretrieval system.

PMID- 8130527
TI  - Pharmacoinformatics: equations for serum drug assay error patterns; implications
      for therapeutic drug monitoring and dosage.
AB  - Pharmacoinformatics is the area of Medical Informatics concerned with modeling
      and simulation of the behavior of drugs, and control of such behavior by
      individualized dosage regimens for each patient to achieve explicitly chosen
      therapeutic goals. The credibility of serum concentration data is a major factor
      in such modeling. The present report examines a more precise way of describing
      the credibility of such data with a collection of polynomial equations, developed
      from routine survey data of the College of American Pathologists, which improve
      the description of the credibility of serum level results when compared to the
      usual practice of describing the assay coefficient of variation in the usual
      manner and then not using such information either in population pharmacokinetic
      modeling or in actual therapeutic drug monitoring. These equations can be used
      until each laboratory can develop its own assay error patterns with its own
      similar polynomial equations.

PMID- 8130528
TI  - The CIO and the medical informaticist: alliance for progress.
AB  - To achieve the full potential of information technology, health care institutions
      must overcome organizational and political barriers that often overshadow
      scientific and technical barriers. The time has come for an alliance between the
      Chief Information Officer (CIO) and medical informatics specialists, or
      informaticists. Organizations that successfully accomplish this alliance will
      position themselves to take advantage of the enormous potential of information
      technology to manage today's cost-quality pressures. This article first reviews
      some of the recent developments in the way health care organizations manage
      information technology. It then describes the traditional, perhaps the natural
      state of affairs, in which there may be tension and conflict between medical
      informaticists and line managers of information systems (IS). Finally, the
      article makes a case for closer collaboration and cooperation between these
      groups, and provides a case study that illustrates one example of such an
      alliance.

PMID- 8130529
TI  - Creating the integrated information infrastructure for the 21st century at the
      University of Washington Warren G. Magnuson Health Sciences Center.
AB  - Successful integrated information systems implementation requires an effective
      marriage of technology and information resources in response to critical
      institutional needs. The University of Washington technical infrastructure,
      developed over the past five years, includes ubiquitous, high-speed network
      access throughout the Health Sciences Center and hospitals, agreement on network
      standards and protocols, uniform interface to common databases (character-based
      and GUI) and network availability of a variety of databases and information
      resources at no charge to the individual. As a result of this heavy institutional
      investment in technical infrastructure, our implementation process will focus on
      expanding the number of available resources as well as developing and refining
      tools and services to enhance the utility of electronic information resources.
      Above all we will study and develop strategies for dealing with the myriad of
      information policy issues which confront and confound us all today.

PMID- 8130530
TI  - Building an information management infrastructure in the 90s: the Vanderbilt
      experiment.
AB  - The course that an organization takes to create a competitive information
      management infrastructure is determined by a series of decisions, each of which
      balances tradeoffs. Key success factors include sequencing projects to reflect
      data requirements; obtaining benefits as cost is incurred; establishing an
      architecture that permits integration of applications; managing project scope;
      and establishing a data friendly culture.

PMID- 8130531
TI  - Clinical, scholarly & campus information hypertext tools at Columbia-Presbyterian
      Medical Center.
AB  - In conjunction with other researchers at Columbia-Presbyterian Medical Center
      (CPMC) we have developed a number of hypertext and free text retrieval computer
      applications aimed at an extremely diverse audience which includes students and
      faculty in a university setting as well as health care providers and patients in
      hospital and clinic settings. Hypertext and free text systems offer features
      which make them ideal for presenting information in a wide variety of contexts;
      however, they also have several major weaknesses which must be addressed before
      these applications can be useful tools. We have learned to maximize the strengths
      and minimize the weaknesses to present material in a manner that is
      individualized to the needs of each user from the research scientist in the lab
      to the patient at the bedside.

PMID- 8130532
TI  - In search of the name.
AB  - Existing communications standards represent person name, date, time, and other
      ubiquitous attributes in various incompatible formats. The electronic medical
      record requires convergence of diverse representational systems toward a single
      communications standard or a harmonized group of standards. The obstacles to
      convergence include disparities in semantic definition, syntax, and
      communications protocols. To facilitate harmonization of existing standards, the
      message standards developers subcommittee of the ANSI HISPP (American National
      Standards Institute Healthcare Informatics Standards Planning Panel) has defined
      a set of common data types to facilitate semantic convergence. The authors
      present the general method used to develop the common data types. The derivation
      of the person name common data type is presented in detail. A general semantic
      model of the person name attribute is developed from observations of
      international usage conventions. A superset of the person name formats of the ACR
      NEMA, ASTM, HL7, NCPDP, MEDIX, and X-12 standards is taken as the provisional
      starting point for a common data type definition. The convergence superset is
      compared with the general semantic model. Highly specialized and/or infrequently
      encountered sub components of the general model are combined into component
      complexes, thereby defining mappings to less rigorous representations. The ANSI
      HISPP common data types are specified for use in a demonstration of a prototype
      object-oriented HL7-DICOM HIS/PACS interface (between hospital information
      systems and imaging systems) at the 1993 Annual Meeting of the Radiological
      Society of North America.

PMID- 8130533
TI  - A planning process for a fast track to IAIMS.
AB  - The strategic planning process that is part of Vanderbilt University's fast track
      to IAIMS is evolving based on feedback from the process itself. Led by a
      committee of VUMC's top management, broad-based sub-committees for
      administration, education, patient care, and research worked initially on the
      following strategic issues: identifying key external pressures that constrain and
      provide opportunities, visioning how VUMC might operate in the future, and
      establishing a mission and high-level goals for information management. Next
      steps include identifying the critical mass of function that will prompt daily
      use of the IAIMS by everyone at VUMC and adding groups to focus on information
      and technology architectures and developing academic informatics. This manuscript
      gives detailed, practical information about the evolution of the planning
      process, committees' responsibilities, working relationships, and lessons
      learned.

PMID- 8130534
TI  - From bench to bedside: research and testing of Internet resources and connections
      in community hospital libraries.
AB  - Access to information becomes more valuable with the continuing proliferation of
      medical knowledge and the increasing economic pressure being experienced by
      health care organizations. This is particularly so for community hospitals in
      rural or isolated areas, where the economic pressures are at least as great as in
      urban areas and where access to information is often inadequate. These conditions
      have implications for the quality of patient care and for economic viability. In
      response to this, the National Library of Medicine, the University of Washington,
      and seven community hospitals in five Pacific Northwest states have joined forces
      in a broad-scale technology diffusion project to facilitate the application of
      research work to clinical care. There are three components to the project: 1) a
      pilot connections component to extend Internet access to the community hospitals,
      2) a research component to test the performance of a client/server model for
      network access to anatomical text and images, and 3) a clinical component to
      develop a registry of DNA diagnostic laboratories facilitating the provision of
      genetic information to clinicians. The pilot connections component is described
      and preliminary findings are reported.

PMID- 8130535
TI  - NetMenu: experience in the implementation of an institutional menu of information
      sources.
AB  - NetMenu is a program, developed at Yale, which enables straightforward access to
      online information systems. NetMenu has been deployed in several diverse settings
      within our medical center. In the hospital, NetMenu is functioning as a front-end
      for our clinical workstation providing access to the hospital information system,
      the clinical laboratory computer, a drug database and several bibliographic
      databases. The medical libraries are utilizing NetMenu for both medical education
      workstations and for scholarly information workstations. This paper describes our
      initial experience in the implementation, support, and maintenance of NetMenu as
      an institutional menu of information sources.

PMID- 8130536
TI  - ARTEMIS: a collaborative framework for health care.
AB  - Patient centered healthcare delivery is an inherently collaborative process. This
      involves a wide range of individuals and organizations with diverse perspectives:
      primary care physicians, hospital administrators, labs, clinics, and insurance.
      The key to cost reduction and quality improvement in health care is effective
      management of this collaborative process. The use of multi-media collaboration
      technology can facilitate timely delivery of patient care and reduce cost at the
      same time. During the last five years, the Concurrent Engineering Research Center
      (CERC), under the sponsorship of DARPA (Defense Advanced Research Projects
      Agency, recently renamed ARPA) developed a number of generic key subsystems of a
      comprehensive collaboration environment. These subsystems are intended to
      overcome the barriers that inhibit the collaborative process. Three subsystems
      developed under this program include: MONET (Meeting On the Net)--to provide
      consultation over a computer network, ISS (Information Sharing Server)--to
      provide access to multi-media information, and PCB (Project Coordination Board)-
      to better coordinate focussed activities. These systems have been integrated into
      an open environment to enable collaborative processes. This environment is being
      used to create a wide-area (geographically distributed) research testbed under
      DARPA sponsorship, ARTEMIS (Advance Research Testbed for Medical Informatics) to
      explore the collaborative health care processes. We believe this technology will
      play a key role in the current national thrust to reengineer the present health
      care delivery system.

PMID- 8130537
TI  - Toward an interim standard for patient-centered knowledge-access.
AB  - Most care-giver "knowledge" needs arise at the point of care and are "patient
      centered." Many of these knowledge needs can be met using existing on-line
      knowledge sources, but the process is too time-consuming, currently, for even the
      computer-proficient. We are developing a set of public domain standards aimed at
      bringing potentially relevant knowledge to the point of care in a straight
      forward and timely fashion. The standards will a) make use of selected items from
      a Computer-based Patient Record (CPR), e.g., a diagnosis and measure of severity,
      b) anticipate certain care-giver knowledge needs, e.g., "therapy," "protocols,"
      "complications," and c) try to satisfy those needs from available knowledge
      sources, e.g., knowledge-bases, citation databases, practice guidelines, and on
      line textbooks. The standards will use templates, i.e., fill-in-the-blank
      structures, to anticipate knowledge needs and UMLS Metathesaurus enhancements to
      represent the content of knowledge sources. Together, the standards will form the
      specification for a "Knowledge-Server" (KS) designed to be accessed from any CPR
      system. Plans are in place to test an interim version of this specification in
      the context of medical oncology. We are accumulating anecdotal evidence that a KS
      operating in conjunction with a CPR is much more compelling to users than either
      a CPR or a KS operating alone.

PMID- 8130538
TI  - Does the medical literature contain the evidence to answer the questions of
      primary care physicians? Preliminary findings of a study.
AB  - OBJECTIVE: To assess the quality of information retrieved in MEDLINE searches
      performed to answer clinical questions of primary care physicians. SETTING:
      Ambulatory rural and nonrural practices. PARTICIPANTS: Active, non-academic
      primary care physicians; professional medical librarians, a general internist.
      DESIGN: Descriptive study in 3 stages: 1) Office Interviews, to record questions
      that arise in primary care practice; 2) Online Searches, to locate information
      that might answer these questions; and 3) Critical Appraisal to determine the
      quality of the information contained in the articles retrieved. MAIN RESULTS: Of
      74 articles judged by clinicians to be relevant to their questions, 2 were
      critical reviews, 14 reported results of randomized controlled trials, and 4
      reported results of cohort studies. The remainder contained weaker evidence: 1
      reported results of a case-control study, 6 were longitudinal case series, 13
      were cross-sectional descriptions of disease, 12 were cross-sectional
      descriptions of diagnostic testing, and 22 were review articles which did not
      meet criteria for a critical review. CONCLUSION: Searching the medical literature
      to answer the questions of primary care physicians was successful in retrieving
      recent, relevant information, and often provided "a clear answer" to the
      question, but the cost of using bibliographic retrieval was high, and fewer than
      a third of the articles retrieved contained high quality evidence.

PMID- 8130539
TI  - Meeting the urgency for document delivery in clinical medicine.
AB  - A Document Delivery library project was designed to improve delivery of
      information to health professionals in the Washington DC/Baltimore area. The
      project goals were to enhance delivery of full text documents and accelerate
      interlibrary loan services. The aim was to provide direct library services in the
      clinical arena by facilitating access to the articles needed by practitioners and
      clinical investigators. The objectives were to (1) design, develop and implement
      a comprehensive Document Delivery System (DDS) for the Library Information System
      (LIS) which included interlibrary loan, photocopy services and facsimile
      transmission capabilities; (2) establish a multi-university Library Knowledge
      Network for resource sharing; and (3) evaluate the project. The DDS and facsimile
      service are described and project data and outcomes are reported. Today, the
      participating libraries can use electronic means to share interlibrary loans.
      Georgetown users have responded favorably to the DDS and Fax services.

PMID- 8130540
TI  - Quality retrieval of the empirical literature: a structured approach.
AB  - The extent and growth of medical knowledge is tremendous. As of December 1990,
      the MEDLINE database had 6.5 million records in its collection, with
      approximately a third added during the last five years. Despite numerous
      innovations, retrieval technology has not kept pace with the exploding numbers of
      authors, articles, journals, books and conferences. A major limiting factor is
      that the basic mechanisms of retrieval systems almost uniformly rely on keyword
      representation and searching. These keywords are either assigned to texts perhaps
      with the assistance of special vocabularies, or appear naturally in these texts.
      In particular no structural or role information is preserved to connect these
      keywords to each other. This paper presents an alternative approach wherein role
      preserving, structured representations are used. This approach has the potential
      to increase retrieval quality.

PMID- 8130541
TI  - Quality evaluation of controlled clinical information service trials.
AB  - Randomized controlled clinical trials are increasingly accepted as tools of
      computer technology assessment and, therefore, quality evaluation of trials has
      great theoretical and practical significance. The purpose of this study was to
      assist the design of evaluation studies and synthesis of published results by
      developing and validating an easy-to-use quality scoring method. The development
      of the new scoring system was based on the available quality evaluation methods
      and the analysis of 19 trial reports registered in the Columbia Registry of
      Controlled Clinical Information Service Trials. First critical aspects and
      afterwards the levels of quality were defined. In spite of the fact that all
      quality requirements were met by some trials, the average overall quality score
      was 52.6 (+/- 8.7) per cent. The minimum score was 37 and the maximum was 72 per
      cent. Data collection and site/sample definition were better in the good quality
      trials, but improvement in statistical analysis was erratic. The quality scoring
      method was validated by using another sample of 20 registered trials. While the
      number of published controlled clinical trials is increasing in medical
      informatics, the analysis was unable to demonstrate a significant positive
      correlation between the quality and year of publication.

PMID- 8130542
TI  - Protection of patient data in multi-institutional medical computer networks:
      regulatory effectiveness analysis.
AB  - Privacy protection is one of the major issues in the development of multi
      institutional clinical information networks. Judicial decisions have confirmed
      patient's rights to protection of a "reasonable expectation of privacy".
      Incorporating this protection into a system requires analysis of appropriate
      models. The National Practitioner Data Bank (NPDB) contains confidential data
      concerning physician competence. The medical profession had substantial input
      into the privacy protection features of the NPDB, which are much more
      comprehensive than those used in many clinical information systems. The NPDB
      represents the privacy protection which physicians expect for their own data.
      Regulatory Effectiveness Analysis can be used to analyze the suitability of the
      NPDB as a model for patient privacy protection. Judicial opinions set public
      policy and legal structures for privacy, and the NPDB provides an inventory of
      useable technical tools. After eliminating minor discontinuities, the NPDB can be
      used as a model to create a useable standard for privacy for multi institutional
      data transfers.

PMID- 8130543
TI  - Critique of an evaluation of software for searching MEDLINE.
AB  - In a previous study, investigators at McMaster University compared 14 ways to
      search the MEDLINE database and concluded that the method that cost the least
      (the National Library of Medicine's ELHILL program) yielded the highest
      proportion of relevant articles, whereas the method that cost the most
      (PaperChase) yielded the least. There are serious defects in the study design
      that invalidate the authors' conclusions.

PMID- 8130544
TI  - Generating MEDLINE search strategies using a librarian knowledge-based system.
AB  - We describe a librarian knowledge-based system that generates a search strategy
      from a query representation based on a user's information need. Together with the
      natural language parser AQUA, the system functions as a human/computer interface,
      which translates a user query from free text into a BRS Onsite search
      formulation, for searching the MEDLINE bibliographic database. In the system,
      conceptual graphs are used to represent the user's information need. The UMLS
      Metathesaurus and Semantic Net are used as the key knowledge sources in building
      the knowledge base.

PMID- 8130545
TI  - Assessment of methodologic search filters in MEDLINE.
AB  - OBJECTIVE: To determine the retrieval characteristics of methodologic textwords
      and MeSH terms in MEDLINE for identifying methodologically sound studies on the
      etiology, prognosis, diagnosis, and prevention and treatment of disorders in
      general adult medicine. DESIGN: Comparison of methodologic search terms and
      phrases for the retrieval of citations in MEDLINE with a manual hand search of
      the literature (the gold standard) for 10 internal and general medicine journals
      for 1986 and 1991. MEASURES: Sensitivity (proportion of methodologically sound
      and correct topic studies retrieved) and specificity (proportion of unsound or
      wrong topic articles not retrieved) of the search strategies. RESULTS: The
      individual terms yielding the best sensitivity for 1991 by purpose category were:
      risk (tw) for etiology; exp cohort studies for prognosis; sensitivity (tw) for
      diagnosis; and clinical trial (pt) for treatment. The corresponding terms for
      1986 were: risk (tw) for etiology; prognosis: (tw) for prognosis; sensitivity
      (tw) for diagnosis; and random: (tw) for treatment. CONCLUSIONS: The performance
      of methodologic MeSH terms and textwords varied greatly in MEDLINE and changed
      from 1986 to 1991. More complex search strategies may be required to optimize
      retrieval.

PMID- 8130546
TI  - Matching references with MEDLINE via TCP/IP.
AB  - Bibliographic references are an important part of databases and information
      resources used by clinicians and biomedical researchers. In addition to the
      obvious clerical advantages of standard references, bibliographic references can
      also be used as links to related items in different data sets. This paper
      describes an effort that involved matching references from a variety of disparate
      databases to canonical MEDLINE references. The references matched were those
      involved in a database unification project which is part of the Mouse Genome
      Informatics effort at The Jackson Laboratory. Software was developed to take
      advantage of a commercially available retrieval engine which accesses MEDLINE on
      CD-ROM disks. The software permits client programs on UNIX/C, and potentially
      other environments, to access unabridged MEDLINE via networks supporting the
      TCP/IP protocols. The matching process described can be used as a model for
      similar efforts with different research or clinical data sets, as well as
      different hardware or software environments.

PMID- 8130547
TI  - Semantic processing in information retrieval.
AB  - Intuition suggests that one way to enhance the information retrieval process
      would be the use of phrases to characterize the contents of text. A number of
      researchers, however, have noted that phrases alone do not improve retrieval
      effectiveness. In this paper we briefly review the use of phrases in information
      retrieval and then suggest extensions to this paradigm using semantic
      information. We claim that semantic processing, which can be viewed as expressing
      relations between the concepts represented by phrases, will in fact enhance
      retrieval effectiveness. The availability of the UMLS domain model, which we
      exploit extensively, significantly contributes to the feasibility of this
      processing.

PMID- 8130548
TI  - An information sources map for Occupational and Environmental Medicine: guidance
      to network-based information through domain-specific indexing.
AB  - This paper describes a prototype information sources map (ISM), an on-line
      information source finder, for Occupational and Environmental Medicine (OEM). The
      OEM ISM was built as part of the Unified Medical Language System (UMLS) project
      of the National Library of Medicine. It allows a user to identify sources of on
      line information appropriate to a specific OEM question, and connect to the
      sources. In the OEM ISM we explore a domain-specific method of indexing
      information source contents, and also a domain-specific user interface. The
      indexing represents a domain expert's opinion of the specificity of an
      information source in helping to answer specific types of domain questions. For
      each information source, an index field represents whether a source might provide
      useful information in an occupational, industrial, or environmental category.
      Additional fields represent the degree of specificity of a source in individual
      question types in each category. The paper discusses the development, design, and
      implementation of the prototype OEM ISM.

PMID- 8130549
TI  - Using the Internet Gopher Protocol to link a computerized patient record and
      distributed electronic resources.
AB  - At Duke University Medical Center, we are developing a prototype clinical
      application for automated patient care plans with integrated links to electronic
      documents and other electronic resources. These links are implemented using the
      Internet Gopher Protocol, an emerging standard for distributed document search
      and retrieval. Use of this protocol permits storage of electronic documents in an
      open, nonproprietary manner. This paper discusses the architecture of the link
      mechanism and presents some of the advantages and disadvantages of the proposed
      method.

PMID- 8130550
TI  - Comparing contents of a knowledge base to traditional information sources.
AB  - Physicians rely on the medical literature as a major source of medical knowledge
      and data. The medical literature, however, is continually evolving and represents
      different sources at different levels of coverage and detail. The recent
      development of computerized medical knowledge bases has added a new form of
      information that can potentially be used to address the practicing physician's
      information needs. To understand how the information from various sources
      differs, we compared the description of a disease found in the QMR knowledge base
      to those found in two general internal medicine textbooks and two specialized
      nephrology textbooks. The study shows both differences in coverage and
      differences in the level of detail. Textbooks contain information about
      pathophysiology and therapy that is not present in the diagnostic knowledge base.
      The knowledge base contains a more detailed description of the associated
      findings, more quantitative information, and a greater number of references to
      peer-reviewed medical articles. The study demonstrates that computerized
      knowledge bases, if properly constructed, may be able to provide clinicians with
      a useful new source of medical knowledge that is complementary to existing
      sources.

PMID- 8130551
TI  - A survey of electronic drug information resources and identification of problems
      associated with the differing vocabularies used to key them.
AB  - Drug information resources are increasingly becoming electronically available.
      They differ in scope, granularity, and purpose. These considerations have shaped
      the selection of dissimilar drug name keys, complicating access. An abbreviated
      and simplified historical context of the development of official controlled
      vocabularies and their relationships is followed by a review of the kinds of
      information available in several electronic drug information resources. The key
      vocabularies used are discussed with examples. Problems using the differing terms
      of the resource vocabularies are identified.

PMID- 8130552
TI  - Desperately seeking data: knowledge base-database links.
AB  - Linking a knowledge-based system (KBS) to a clinical database is a difficult
      task, but critical if such systems are to achieve widespread use. The Columbia
      Presbyterian Medical Center's clinical event monitor provides alerts,
      interpretations, research screening, and quality assurance functions for the
      center. Its knowledge base consists of Arden Syntax Medical Logic Modules (MLMs).
      The knowledge base was analyzed in order to quantify the use and impact of KBS
      database links. The MLM data slot, which contains the definition of these links,
      had almost as many statements (5.8 vs. 8.8, ns with p = 0.15) and more tokens
      (122 vs. 76, p = 0.037) than the logic slot, which contains the actual medical
      knowledge. The data slot underwent about twice as many modifications over time as
      the logic slot (3.0 vs. 1.6 modifications/version, p = 0.010). Database queries
      and updates accounted for 97.2% of the MLM's total elapsed execution time. Thus,
      KBS-database links consume substantial resources in an MLM knowledge base, in
      terms of coding, maintenance, and performance.

PMID- 8130553
TI  - Application of a multilevel access model in the development of a security
      infrastructure for a clinical information system.
AB  - A number of security models including the military model, the Institute of
      Medicine model, and the matrix model have been utilized, or proposed, for
      protecting clinical information systems. These models have a number of
      limitations, however, and of particular concern, they focus on security as
      opposed to access. In this paper we describe a multilevel access model which can
      overcome some of these limitations. This model is currently being utilized in the
      development of an improved security infrastructure for a clinical information
      system.

PMID- 8130554
TI  - Unifying heterogeneous distributed clinical data in a relational database.
AB  - Access to clinical data which are distributed among multiple satellite
      information systems is crucial to delivering better care and reducing costs in
      many hospitals and medical centers. An integrated view of these data is needed to
      reduce the effort of users requiring data from multiple systems. We have
      addressed the issue of distributed data integration while developing both
      production and research decision-support applications. We describe an ideal
      integration solution, obstacles to realizing this solution, and our integration
      requirements and architecture. Our focus is a description of our specific schema
      and data integration techniques. We conclude with an analysis of our approach.

PMID- 8130555
TI  - CECIL: a database for storing and retrieving clinical and molecular information
      on patients with Alport syndrome.
AB  - CECIL is a database that stores clinical and molecular information on patients
      with Alport syndrome. The clinical component of CECIL is specific to Alport
      syndrome; the component that stores and manipulates molecular data can be used
      for any disease caused by a gene mutation, such as cystic fibrosis. While
      offering the ability to retrieve patient data through compound Boolean queries,
      CECIL also offers the ability to manipulate sequence information in various ways.
      In particular, CECIL can perform an augmented sequence alignment of an abnormal
      (patient) DNA sequence with a reference sequence. CECIL is currently being used
      by members of the International Alport Syndrome consortium. We describe CECIL's
      features and discuss the design decisions made in generalizing CECIL's
      architecture.

PMID- 8130556
TI  - Development of a statewide trauma registry using multiple linked sources of data.
AB  - In order to develop a cost-effective method of injury surveillance and trauma
      system evaluation in a rural state, computer programs were written linking
      records from two major hospital trauma registries, a statewide trauma tracking
      study, hospital discharge abstracts, death certificates, and ambulance run
      reports. A general-purpose database management system, programming language, and
      operating system were used. Data from 1991 appeared to be successfully linked
      using only indirect identifying information. Familiarity with local geography and
      the idiosyncracies of each data source were helpful in programming for effective
      matching of records. For each individual case identified in this way, data from
      all available sources were then merged and imported into a standard database
      format. This inexpensive, population-based approach, maintaining flexibility for
      end-users with some database training, may be adaptable for other regions. There
      is a need for further improvement and simplification of the record-linkage
      process for this and similar purposes.

PMID- 8130557
TI  - Data management in multi-center clinical trials and the role of a nation-wide
      computer network. A 5 year evaluation.
AB  - Multidisciplinary collaboration in multi-center trials needs a formalized data
      management structure to ensure true progress monitoring and high quality research
      data. Cadans, a customized facility for data management, related to the
      Interuniversity Cardiology Institute of the Netherlands, designed a computer
      based data management system for multidisciplinary multi-center collaborative
      research projects. In this paper we describe the system and the role of
      integrated access to research databases on a data network. Areas of concern are
      also discussed.

PMID- 8130558
TI  - Creation of state-level Medicare database for healthcare evaluation applications.
AB  - The Health Care Quality Improvement Initiative (HCQII) of the Health Care
      Financing Administration (HCFA) calls for Professional Review Organizations
      (PROs) to undertake pattern analysis of large administrative datasets for the
      purposes of quality of care assessment. The limitations of such administrative
      databases (primarily the MEDPAR file and derivatives thereof) include
      impoverished information regarding clinical attributes of Medicare enrollees and
      the process and outcome of their healthcare. This paper describes preliminary
      efforts to address this problem by the creation of a database, the PRO
      Concatenated Database (PCD), from the pooled implicit judgment review data of
      four Peer Review Organizations (PROs). The data elements comprising the PCD were
      carefully selected to provide important information regarding quality and
      appropriateness of care. Preliminary inter-state comparative studies employing
      the PCD are discussed. A method is also described by which the analytical power
      of state-level databases may be enhanced by linkage to state-level Modeled MEDPAR
      data which are issued by HCFA and contain patient-level risk-adjusted mortality
      data. This approach to the acquisition of data whose clinical content is enriched
      may prove to be particularly useful to the PRO community during the pattern
      analysis phase of the HCQII. Such analyses will evolve into more detailed studies
      involving primary data collection followed by dissemination of the results to
      local healthcare providers. In this manner, the PCD may facilitate rapid feedback
      regarding the effectiveness of healthcare delivery to the local community.

PMID- 8130559
TI  - An Ambulatory Service Weighting System: making sense out of millions of
      ambulatory claims.
AB  - This paper describes a cost-based relative value scale to use in measuring the
      intensity and costs of hospital services, regardless of the place of service-
      inpatient or outpatient. The Pittsburgh Research Institute's AMBULATORY SERVICE
      WEIGHTING SYSTEM (ASWS) is a service-driven relative value scale. The major
      components of the system are: 1) a classification of services and procedures
      provided in ambulatory settings; 2) a cost-based relative intensity weight for
      each service; and 3) a computerized system that assigns a relative weight to each
      ambulatory patient based on the specific services recorded on the patient bill
      and rendered during a particular visit or in multiple encounters. Computerized
      decision rules are also incorporated as edits to adjust for inconsistent revenue
      or procedure coding practices. The system basically standardizes the millions of
      outpatient claims received by third party payors so that intensity can be
      measured consistently across providers, and payment systems can be modified
      accordingly. The ASWS identifies service intensity on the same relative value
      scale as inpatient care, and thus, it can serve as a site-neutral classification
      of health care services for prospective payment and utilization management as
      well as a measure of resource intensity.

PMID- 8130560
TI  - Linking the Computerized Severity Index (CSI) to coded patient findings in the
      HELP system patient database.
AB  - The Computerized Severity Index (CSI) is a commercially available scoring system
      for hospital inpatients. Trained abstractors review the patient's paper medical
      record and enter the diagnoses and relevant physiological facts. The HELP (Health
      Evaluation Through Logical Processing) System at LDS Hospital stores patient data
      in discrete codes. We believe that HELP's coded patient database may drive an
      automatic version of CSI without the need for manual input. This descriptive
      study examines the nature and depth of the HELP System patient findings needed to
      implement an automatic CSI.

PMID- 8130561
TI  - Database access and problem solving in the basic sciences.
AB  - This study examined the potential contribution that access to a database of
      biomedical information may offer in support of problem-solving exercises when
      personal knowledge is inadequate. Thirty-six medical students were assessed over
      four occasions and three domains in the basic sciences: bacteriology,
      pharmacology, and toxicology. Each assessment consisted of a two-pass protocol in
      which students were first assessed for their personal knowledge of a domain with
      a short-answer problem set. Then, for a sample of problems they had missed, they
      were asked to use a database, INQUIRER, to respond to questions which they had
      been unable to address with their personal knowledge. Results indicate that for a
      domain in which the database is well-integrated in course activities, useful
      retrieval of information which augmented personal knowledge increased over three
      assessment occasions, even continuing to increase several months after course
      exposure and experience with the database. For all domains, even at assessments
      prior to course exposure, students were able to moderately extend their ability
      to solve problems through access to the INQUIRER database.

PMID- 8130562
TI  - Words or concepts: the features of indexing units and their optimal use in
      information retrieval.
AB  - Words or Concepts, which are a better choice for indexing the contents of
      documents? The answer depends on what method is used for retrieval. This paper
      studies the effects of using canonical concepts versus document words in
      different retrieval systems with a testing collection of MEDLINE documents. In
      our tests, for a retrieval system which does not use any human knowledge, using
      words yielded better retrieval results, while using concepts suffered from a
      vocabulary difference between canonical expressions of concepts and non-canonical
      words in queries or documents. For a system which depends on the UMLS synonym set
      for a mapping from queries or documents to canonical concepts, the retrieval
      results were slightly better than the case of not using the synonyms, but still
      worse than the systems using words. For the systems which automatically "learn"
      empirical connections between words and concepts from examples in the testing
      collection, the vocabulary problem was effectively solved, and the results of
      using concepts were competitive or better, compared to those using words.

PMID- 8130563
TI  - Patient-centered computing: can it curb malpractice risk?
AB  - The threat of a medical malpractice suit represents a major cause of career
      dissatisfaction for American physicians. Patient-centered computing may improve
      physician-patient communications, thereby reducing liability risk. This review
      describes programs that have sought to enhance patient education and involvement
      pertaining to 5 major categories of malpractice lawsuits: Diagnosis, medications,
      obstetrics, surgery, and treatment errors.

PMID- 8130564
TI  - Automated translation between medical vocabularies using a frame-based
      interlingua.
AB  - The integration of clinical systems almost always requires a translation phase,
      where vocabularies are compared and the similar concepts are matched. The lack of
      standards in the area of medical concept representation makes this task very
      difficult. The authors describe the development of a frame-based application that
      automatically translates terms found in one vocabulary to another. The
      application implements an innovative scoring algorithm that ranks the best
      matches using an exponential scale. Preliminary results and the comparison
      against a manual process in the same domain are also discussed.

PMID- 8130565
TI  - Developing a standard data structure for medical language--the SNOMED proposal.
AB  - The Systematized Nomenclature of Medicine, Third Edition, SNOMED International,
      is a comprehensive structured nomenclature of human and veterinary medicine, the
      terms of which are detailed, fine grained and semantically typed. Terms are
      assigned to eleven independent modules (fields), each of which is systematized.
      Terms may be linked to on another to represent complex entities or manifestations
      or alternately complex terms dissected into their elemental parts. Terms are
      illustrated utilizing a frame representation. Efforts are in progress to build
      both a conceptual graph and a frame-based semantic network encompassing each
      SNOMED term, effectively building a knowledge base. In this way, the knowledge
      contained in each alphanumeric representation is made explicit. SNOMED is a
      linked data structure capable of faithfully representing the activities,
      observations and diagnoses found in the medical record in a computer processable
      form.

PMID- 8130566
TI  - Representation of nursing terms for the description of patient problems using
      SNOMED III.
AB  - We conducted an experiment to determine if the terms recorded by nurses in the
      patient chart to describe patient problems could be represented using SNOMED III
      terms. The data sources for the patient problems were the nurses' progress notes
      and nursing care plans from 485 patient encounters in three diverse settings
      (NR02215). We entered the nursing terms into a relational database. We loaded the
      SNOMED III terms into a relational database and created a word index. We
      determined matches by identifying the English description of the SNOMED III term
      that best matched the term charted by the nurses. Sixty-nine percent of the
      nursing terms in the test subset were matched using one or more SNOMED III terms.
      We identified redundant SNOMED III terms for several nursing terms including fear
      and diarrhea. Our results suggest that terms recorded by nurses in the patient
      chart can be represented using SNOMED III terms. Further enhancement and
      refinement will improve the domain completeness of SNOMED III as a controlled
      healthcare vocabulary and decrease redundancies.

PMID- 8130567
TI  - How useful is the UMLS metathesaurus in developing a controlled vocabulary for an
      automated problem list?
AB  - We are developing a set of problem list phrases to be used in the automated
      problem list of a prototype clinical computing system. Because of the large
      number of terms in the Unified Medical Language System (UMLS) and the links
      between them, we are experimenting with the use of the UMLS as the foundation for
      our problem list phrase set. We have found the UMLS to be very useful for this
      project, but that it lacks many phases clinicians wish to include in the problem
      list. Internal linkages between phrases provided in the UMLS are not well suited
      to our needs. We plan to continue our use of the UMLS but to add problem list
      phrases and linkages between phrases to support browsing and decision support
      applications.

PMID- 8130568
TI  - Structuration and acquisition of medical knowledge. Using UMLS in the conceptual
      graph formalism.
AB  - The use of a taxonomy, such as the concept type lattice (CTL) of Conceptual
      Graphs, is a central structuring piece in a knowledge-based system. The knowledge
      it contains is constantly used by the system, and its structure provides a guide
      for the acquisition of other pieces of knowledge. We show how UMLS can be used as
      a knowledge resource to build a CTL and how the CTL can help the process of
      acquisition for other kinds of knowledge. We illustrate this method in the
      context of the MENELAS natural language understanding project.

PMID- 8130569
TI  - A conceptual model for information retrieval with UMLS.
AB  - Information retrieval in large information databases is a non-deterministic
      process which needs a sequence of search steps generally. One of the main
      problems to which the end-users are faced is to parse efficiently their questions
      into the query language that the computer systems allow. Conceptual graphs were
      initially designed for natural language analysis and understanding. Due to their
      closeness to semantic networks, their expressiveness is powerful enough to be
      applied to knowledge representation and use by computer systems. This work
      demonstrates that conceptual graphs are a suitable means to model the end-users
      querieson the basis of the thesaurus and the semantic network of the UMLS
      project.

PMID- 8130570
TI  - The ranking algorithm of the Coach browser for the UMLS metathesaurus.
AB  - This paper presents the novel ranking algorithm of the Coach Metathesaurus
      browser which is a major module of the Coach expert search refinement program. An
      example shows how the ranking algorithm can assist in creating a list of
      candidate terms useful in augmenting a suboptimal Grateful Med search of MEDLINE.

PMID- 8130571
TI  - Using the UMLS Semantic Network as a basis for constructing a terminological
      knowledge base: a preliminary report.
AB  - Sharing and reuse of knowledge bases is recognized in Artificial Intelligence and
      Medical Informatics as beneficial, but difficult. Reusing an existing knowledge
      base can save considerable time and effort during the knowledge engineering
      phase, and facilitates integration of systems. However, the degree to which
      knowledge can be shared among different applications is still mainly an empirical
      question. In this paper, we describe the preliminary results of our attempt to
      reuse the UMLS Semantic Network as an ontology for the knowledge base of a
      patient education system.

PMID- 8130572
TI  - From ICD9-CM to MeSH using the UMLS: a how-to guide.
AB  - One purpose of the Unified Medical Language System (UMLS) is to facilitate
      conversion of terms from one controlled medical vocabulary to another. We
      examined our ability to convert International Classification of Diseases, 9th
      Edition, Clinical Modifications (ICD9-CM) to Medical Subject Headings (MeSH)
      using the UMLS. We describe a method which mapped 30.4% of ICD9-CM to UMLS. Of
      these, 95.0% were linked to MeSH, of which translation was straightforward in
      90.4%. We discuss the use of these translations for retrieval from MeSH-indexed
      databases, such as Medline.

PMID- 8130573
TI  - Mendelian inheritance in man: diagnoses in the UMLS.
AB  - Because they deal with many distinct but rare inheritance diseases, geneticists
      have difficulty translating from their codes to other biomedical coding schemes.
      The objective of this research was to investigate the potential uses and
      difficulties of using the UMLS Metathesaurus for genetic diagnoses and to make
      recommendations to UMLS developers for improvements in UMLS for common genetic
      disorders. The 110 most common Mendelian Inheritance in Man disorders from the
      Missouri Genetic Disease Program over the period of one year were translated into
      MeSH, ICD and SNOMED. The more common diseases are more likely to be mapped than
      the rarer ones. Diseases with a proven genetic inheritance pattern are more
      likely to be mapped than those with speculated inheritance patterns.
      Approximately one third of all diagnoses were not mapped across all three coding
      schemes in Meta-1.2. The ICD coding scheme was found to be too broad to be
      meaningful for genetic diagnosis or epidemiological purposes. MeSH and SNOMED
      need to be made more specific and complete, and all of the new version of SNOMED
      needs to be included in the Metathesaurus.

PMID- 8130574
TI  - Real and imagined barriers to an electronic medical record.
AB  - We developed an electronic medical record for ambulatory patients as part of the
      integrated clinical information system at Beth Israel Hospital. During the four
      years since it was installed, clinicians have entered 76,060 patient problems,
      137,713 medications, and 33,938 notes. Residents, who had to type notes in
      themselves, entered 49.5% of their notes into OMR. Several factors that we had
      predicted would be barriers to an electronic medical record, such as clinician
      reluctance to type or perform data entry, have not proved to be significant
      problems. Other anticipated barriers, such as difficulties with dual charting on
      paper during transition to an electronic medical record, have been realized. The
      major unexpected barrier that has been encountered is increased clinician concern
      about the privacy and security of full text notes relative to other data elements
      in the clinical information system. We have attempted to modify the electronic
      medical record so as to overcome some of these barriers.

PMID- 8130575
TI  - "Pre-medical" informatics.
AB  - Many authors have presented arguments in the recent medical literature discussing
      the premedical preparation of medical students. Much of this work seems to center
      upon the need to balance the strong science concentration with an increased
      emphasis on humanities courses. This paper investigates another potential
      shortcoming of premedical education, that of information literacy. It defines the
      problem, argues its existence, and proposes the ready availability of a solution.

PMID- 8130576
TI  - Are computer-based educational materials recognized as publications? An analysis
      of promotion documents at American medical colleges.
AB  - A generalized perception exists that faculty will not be properly rewarded for
      efforts in developing computer-based educational materials. Faculty governed by
      traditional promotion and tenure systems thus may be reluctant to devote energies
      towards development of these materials. Recent national panels on educational
      reform have called for a reexamination of academic reward structures to insure
      that faculty receive appropriate scholarly recognition for materials developed in
      these new formats. A study of policy documents from accredited medical colleges
      in the United States was conducted to determine the extent to which academic
      health science institutions have adopted policies to grant recognition of
      computer-based materials equivalent to that accorded traditional print
      publications. Results revealed that while some progress has been made by leading
      edge institutions, in three-quarters of the institutions, development of computer
      based educational materials is considered evidence in support of teaching, not
      the more highly rewarded research or scholarly activity.

PMID- 8130577
TI  - The Centennial Patient Care Program: binding patient, student, and clinician
      teacher in a learning triad.
AB  - The University of Chicago is building a technology-based clinical environment to
      provide a longitudinal experience for patients and medical students. This
      environment uses an open systems, computer communication and information support
      network to forge an interactive education and care relationship between patient,
      medical student, and clinical faculty mentor. The project proactively addresses
      some of the most important activities required to reform both the health care and
      medical education systems: anchoring patient care in a generalist setting;
      educating medical students in outpatient medicine; fostering primary care as a
      career choice; and using medical informatics as a tool rather than as an end in
      itself. Moreover, the project effectively deploys concepts such as patient
      centered education, student-based learning, and mentored teaching experiences.
      This paper reports the curricular, pedagogical, and technological motivations and
      framework under which the project was designed, and describes the process that a
      patient-student-clinician/teacher triad will experience as participants in this
      program.

PMID- 8130578
TI  - Supporting patient centered computing through an undergraduate nursing
      informatics curriculum stage III.
AB  - The patient has been one of the focal points of the process followed to design,
      implement, and evaluate an integrated informatics curriculum in a baccalaureate
      nursing program. This paper describes the third stage of a process to design the
      informatics nursing courses. A challenge is to structure the nursing informatics
      curriculum so as to enhance the patient care process. A number of strategies were
      used to focus the curriculum, students, and faculty around the patient. The basic
      components of the framework are information, technology, and clinical care
      process. The clinical care process which emphasizes the patient is an inherent
      part of the conceptual framework in all aspects of the curriculum. Therefore the
      faculty has ensured a blend of information, technology, and the clinical care
      process throughout the curriculum.

PMID- 8130579
TI  - Using the UMLS to represent medical curriculum content.
AB  - Recent innovations in medical education have highlighted the need for faculty
      involved with the curriculum to carefully examine curricular content with goals
      of detecting omissions and unwanted redundancies of subject matter, adding and
      integrating new content, and deleting old content. A number of medical schools
      have attempted to deal with these issues by developing a database of curricular
      content information, most often using faculty- or student-selected keywords to
      represent each unit of instruction. However, several problems have been
      identified with this method, and achieving the goals mentioned above remains a
      formidable task. This paper outlines an alternative method that uses the
      resources of the UMLS to characterize a medical concept by the semantic types of
      its co-occurring terms. This approach can facilitate achievement of the
      aforementioned goals.

PMID- 8130580
TI  - Curriculum Analysis Tools (CATs): a cooperative approach to the design of
      curriculum databases.
AB  - In 1990, a small group of dental schools agreed to pool their resources and
      cooperate in the design and programming of curriculum analysis software. After
      two and one half years, the consortium which was formed has grown to include over
      50 institutions. Its efforts have been endorsed by the American Association of
      Dental Schools and it is now beta testing its first software product, known as
      CATs, which is an acronym for Curriculum Analysis Tools. The process by which the
      software has been developed, as well as its current design, offers a unique blend
      of flexibility and creativity which could perhaps be adopted by other health
      professions.

PMID- 8130581
TI  - CaseLog: semantic network interface to a student computer-based patient record
      system.
AB  - We have developed a computer program called CaseLog, which serves as an
      exemplary, computer-based patient record (CPR) system. The program allows for the
      introduction of the students to issues unique to patient record systems. These
      include record security, unique patient identifiers, and the use of controlled
      vocabularies. A particularly challenging aspect of the development of this
      program was allowing for student entry of controlled vocabulary terms. There were
      four goals we wished to achieve: students should be able to find the terms they
      are looking for; once a term has been found, it should be easy to find
      contextually related terms; it should be easy to determine that a sought-for term
      is not in the vocabulary; and the structure of the vocabulary should be
      dynamically altered by contextual information to allow its use for a variety of
      purposes. We chose a semantic network for our vocabulary structure. Within the
      processing power of the equipment we were working with, we achieved our goals.
      This paper will describe the development of the vocabulary, the design of the
      CaseLog program, and the feedback from student users of the program.

PMID- 8130582
TI  - UCSD's MedPics: implementation and impact on the curriculum.
AB  - MedPics is a computer-based image delivery system with supporting text fields and
      on-screen graphics to assist in key feature identification. It has been used by
      the University of California, San Diego as an integral part of the Human Disease
      course since 1992. Initially created to support pathology and histology, the
      program has now expanded to include hematology. MedPics has had a positive impact
      on the second year curriculum for which it was created. Moreover, use of this
      program has improved student attitudes toward computer-based resources and
      increased faculty interest in instructional development.

PMID- 8130583
TI  - Maximizing the utilization and impact of medical educational software by
      designing for local area network (LAN) implementation.
AB  - The design, development and implementation of medical education software often
      occurs without sufficient consideration of the potential benefits that can be
      realized by making the software network aware. These benefits can be considerable
      and can greatly enhance the utilization and potential impact of the software.
      This article details how multiple aspects of the IMMEX problem solving project
      have benefited from taking maximum advantage of LAN resources.

PMID- 8130584
TI  - Conceptual change and computer-assisted instruction.
AB  - We conducted a study to determine whether a computer-assisted instruction program
      in neuroanatomy helped first-year medical students to form biomedical concepts,
      and to correct their misconceptions. Using questionnaires and interviews, we
      elicited concepts and misconceptions held by the students, in the domain of
      cranial nerve anatomy. The computer program exposed the students to the
      information they required to answer the scenario-based questions. Our study found
      that the students' number and types of misconceptions did not decrease after use
      of the computer-assisted instruction program. Our findings suggest that designers
      of computer-assisted instruction programs should determine the common
      misconceptions that student hold, and should target the programs to correct these
      misconceptions.

PMID- 8130585
TI  - Acceptance of direct physician access to a computer-based patient record in a
      managed care setting.
AB  - Kaiser Permanente Mid-Atlantic States has developed a fully integrated outpatient
      information system which currently runs on an IBM ES9000 on a VM platform written
      in MUMPS. The applications include Lab, Radiology, Transcription, Appointments.
      Pharmacy, Encounter tracking, Hospitalizations, Referrals, Phone Advice, Pap
      tracking, Problem list, Immunization tracking, and Patient demographics. They are
      department specific and require input and output from a dumb terminal. We have
      developed a physician's work station to access this information using PC
      compatible computers running Microsoft Windows and a custom Microsoft Visual
      Basic 2.0 environment which draws from these 14 applications giving the physician
      a comprehensive view of all electronic medical records. Through rapid
      prototyping, voluntary participation, formal training and gradual implementation
      we have created an enthusiastic response. 95% of our physician PC users access
      the system each month. The use ranges from 0.2 to 3.0 screens of data viewed per
      patient visit. This response continues to drive the process toward still greater
      user acceptance and further practice enhancement.

PMID- 8130586
TI  - Initial validation of a test of spatial knowledge in anatomy.
AB  - The authors have developed HERCULES, a computer-based test designed to assess the
      spatial, non-verbal components of knowledge in anatomy. The test consists of two
      tasks, each requiring subjects to estimate the vertical level in the body of a
      set of color, cross-sectional images. In Task 1, subjects make the estimate based
      on a limited number of clues, where each clue is an anatomical structure that
      appears in the cross-section. In Task 2, subjects estimate the level based on a
      view of the cross-section with all structures shown. A validation study of this
      test using six images for each task was performed with preclinical medical
      students, fourth year medical students, and experienced teachers of anatomy as
      subjects. Results indicate that the exercise is at an appropriate level of
      difficulty and that a somewhat longer test than used in this study would be
      adequately reliable for use in actual assessment. The test appears to
      discriminate the expert faculty from more novice students and thus exhibits an
      aspect of validity that is very important in assessment exercises of this type.

PMID- 8130587
TI  - Patient simulation using seamless digital video.
AB  - This manuscript describes a method for using digital-video technology to create
      patient simulations in which the simulated patient is always active on the
      computer screen. We outline the technical method we have developed, and we
      present the lessons learned in applying the method to develop a prototype patient
      simulation.

PMID- 8130588
TI  - Improving the quality of patient care: the role of patient preferences in the
      clinical record.
AB  - Patients are an important but overlooked participant in health information
      management. Patients serve as a source of self-monitoring data and for self
      report of essential judgments such as preference for treatment and preferences
      for clinical outcomes. As the deliberations regarding the Computer-Based Patient
      Record initiative continue, decisions must be made about what patient-specific
      information will be entered in the record. In consideration of the mounting
      evidence that patient preferences represent an essential component in many health
      care decisions, it is timely to advocate for including patient preferences in the
      patient record. This represents one aspect of the patient role in health care
      information management.

PMID- 8130589
TI  - A teleconferencing system.
AB  - Training of health professionals commonly involves multiple sites in order to
      best utilize the available clinical material. However, this makes it difficult to
      achieve continuity in the presentation of didactic material. We have installed a
      teleconferencing system using high speed switching Asynchronous Transfer Mode
      (ATM) for transmission of audio, video and digital images. We aimed to emulate
      the ambience of a classroom at three sites in the training program. We are now in
      the first of a four phase evaluation trial with US West. Experience with
      implementing a new teleconferencing system using ATM switching is described.

PMID- 8130590
TI  - Mechanisms for exchange of image data to support distant medical consultation.
AB  - The VA has developed an integrated infrastructure to support the exchange of
      medical data, including images and text report data, between medical centers.
      This capability is expected to support teleconsulting and meet a variety of
      existing medical staffing and consultation needs. Consultation from distant
      locations requires at least the same complete integrated patient record available
      to onsite physicians. Several mechanisms are being explored to support distant
      medical consultation. Multimedia extensions to the VA's electronic mail system
      have been developed to allow images and other data objects to be included in
      electronic mail messages. Another approach that has been prototyped is to extend
      existing local imaging networks to produce more widely distributed imaging
      systems. These approaches will be described and discussed.

PMID- 8130591
TI  - A data interchange standard for clinical neurophysiology.
AB  - A Standard Specification for Transferring Digital Neurophysiological Data Between
      Independent Computer Systems (Designation E 1467-92) has been developed. The
      specification defines a common representation of all of the data associated with
      a complete clinical study, including digitized neurophysiological waveforms,
      textual annotations and interpretive reports. Patterned after existing, related
      healthcare data interchange standards, it will facilitate data interchange
      between neurophysiological instruments, computer systems within the
      neurophysiology laboratory, other information systems in the hospital, and
      outside healthcare facilities or research laboratories.

PMID- 8130592
TI  - Description and representation of segmented renal arteries from angiograms.
AB  - This paper presents the first prototype of a system that uses syntactic
      techniques to describe normal and abnormal aspects of segmented renal arteries
      from angiographic images. The system is one part of a full understanding system
      devoted to the interpretation of angiograms. Its purpose is to provide symbolic
      descriptions of lesions that can further contribute to an accurate diagnosis from
      the image. The prototype consists of a modular system that takes artery outlines
      as input and provides a structural description of the artery as output in the
      framework of a precise quantification scheme. Each module yields heuristic
      parameters that influence the resulting description. The system is intended to be
      a tool to study independently the role of these different parameters in the inter
      and intra observer variability.

PMID- 8130593
TI  - Lossy compression in nuclear medicine images.
AB  - The goal of image compression is to reduce the amount of data needed to represent
      images. In medical applications, it is not desirable to lose any information and
      thus lossless compression methods are often used. However, medical imaging
      systems have intrinsic noise associated to it. The application of a lossy
      technique, which acts as a low pass filter, reduces the amount of data at a
      higher rate without any noticeable loss in the information contained in the
      images. We have compressed images of nuclear medicine using the discrete cosine
      transform algorithm. The decompressed images were considered reliable for visual
      inspection. Furthermore, a parameter was computed from these images and no
      discernible change was found from the results obtained using the original
      uncompressed images.

PMID- 8130594
TI  - A conceptual model for clinical radiology reports.
AB  - The structural and informational content of clinical radiology reports was
      examined to develop a comprehensive representational schema of the concepts in
      the domain. The model involves several different conceptual levels, ranging from
      the high level description of the report to the lower level description of the
      clinical concepts contained in the reports and the specification of the terms
      used to express the concepts. The design of an adequate structured representation
      for the domain has important implications for the design of the electronic
      patient record, for the unification of different controlled vocabularies by
      enabling them to be mapped to one common representation, and for the facilitation
      of natural language processing of clinical reports so that coded data may be
      obtained.

PMID- 8130595
TI  - Design and evaluation of multimedia stimuli to evoke clinical concepts.
AB  - Continuous speech recognition systems have the potential to facilitate clinical
      data entry, but evaluating them rigorously is difficult. We describe a tool to
      aid evaluators of such systems. The tool is a HyperCard stack with stimuli
      consisting of pictures, sounds and the minimum of words to evoke 20 QMR physical
      findings. Despite using up to four different stimuli to communicate each finding
      and piloting the material on six subjects, eight test subjects made a total of 66
      errors (42%) in interpreting the 20 sets of stimuli, of which 22 errors (14%)
      were serious. These results are relevant to those designing interfaces for
      decision-support, tutorial and student testing systems.

PMID- 8130596
TI  - Image Engine: an object-oriented multimedia database for storing, retrieving and
      sharing medical images and text.
AB  - This paper describes Image Engine, an object-oriented, microcomputer-based,
      multimedia database designed to facilitate the storage and retrieval of digitized
      biomedical still images, video, and text using inexpensive desktop computers. The
      current prototype runs on Apple Macintosh computers and allows network database
      access via peer to peer file sharing protocols. Image Engine supports both free
      text and controlled vocabulary indexing of multimedia objects. The latter is
      implemented using the TView thesaurus model developed by the author. The current
      prototype of Image Engine uses the National Library of Medicine's Medical Subject
      Headings (MeSH) vocabulary (with UMLS Meta-1 extensions) as its indexing
      thesaurus.

PMID- 8130597
TI  - Integrating Hospital Information Systems. The challenges and advantages of (re
      )starting now.
AB  - With the new technologies available today, more complex and useful Hospital
      Information Systems (HIS) can be designed and implemented. These new technologies
      have allowed that information from different sources and nature such as
      documents, images and signals be integrated within a single environment. Open
      standards, reliable networks, powerful hardware and software and lower prices are
      among the issues that make all this possible. One of the main issues is what to
      do with old systems that do not adhere to this new HIS concept. At the Heart
      Institute (InCor), a decision was made towards starting developing a new system
      called I3S. This paper gives a brief description of that system.

PMID- 8130598
TI  - A multimedia preference-assessment tool for functional outcomes.
AB  - Functional outcomes of clinical trials are often reported as number of
      dependencies in activities of daily living (ADLs). Quality-weighting for the ADLs
      has not been reported. We designed and pilot-tested ADLIB (ADL Index Builder), a
      multimedia computer program, that presents ADL health states to subjects and
      elicits from subjects a rating for the quality of life of each health state.
      Subjects, who were patients over age 50 without previous computer experience,
      found the program easy to use. Health care professionals specializing in
      geriatrics confirmed that the ADL presentations used in the program are in accord
      with typical practice in scoring ADLs. We plan to use the program to obtain
      population-based preference ratings that can be used to assess efficacy of
      clinical trials and to provide quality-weights for cost-effectiveness analysis.

PMID- 8130599
TI  - An ODA-based coder/decoder for multimedia medical documents.
AB  - This paper describes the prototype of a coder/decoder based on the Open Document
      Architecture (ODA) standard for management of medical documents, as well as the
      working environment in which it has been developed. The prototype has been
      assessed in an X-Windows-equipped workstation with a relational database
      containing patient folders (text and still images) from the departmental
      information system of the liver transplantation unit.

PMID- 8130600
TI  - The Problem-Oriented Medical Synopsis: a patient-centered clinical information
      system.
AB  - A clinical information system consists of four major components: the clinical
      database, decision support, data analysis (including outcomes), and the
      development system. We have created such a system using generally available
      database methodology. The clinical database, for record-keeping, is called the
      Problem-Oriented Medical Synopsis, and is quite an old system, originating in
      1966. We describe the suitability of a problem-oriented model of clinical records
      management to the relational model of database design, and describe our
      experience with the database as a departmental information system for patient
      care and outcomes research. Hybrid, or partially problem-oriented, databases
      represent an acceptable approach to clinical record-keeping.

PMID- 8130601
TI  - Family practice informatics: research issues in computerized medical records.
AB  - There are unique features of family and general practice which lead to unique
      issues in medical informatics for family physicians. The nature of practice in
      office based community settings and the discipline of dealing with all ages,
      sexes, and health conditions over the lifetime of a patient and his/her family
      lead to models of the thinking that are different from those used in most other
      specialties. Research is urgently needed to verify the models of thinking that
      physicians use during patient care encounters and the associated nomenclatures
      and classifications which support them. User interfaces need to be optimized for
      accuracy and speed. Standards for medical records computing in family practice
      need testing and validation.

PMID- 8130602
TI  - Integrating QMR with a computer-based patient record.
AB  - Most diagnostic decision support (DDS) systems are used as stand-alone
      applications. At present, the physician can only benefit from the suggestions of
      a DDS system if he is sufficiently motivated to re-enter patient data and run a
      diagnostic case analysis. If data from a computer-based patient record (CBPR)
      could be made available electronically to a DDS system, the use of that DDS
      system may become much more practical. Integrating a CBPR with a DDS system
      requires a mapping between two different data structures and dictionaries. We
      have explored a strategy to create a mapping between our CBPR and QMR. Our
      research has provided more general insight in the potential and limitations of
      such a mapping.

PMID- 8130603
TI  - Validation of measurement of regional myocardial perfusion in humans by ultrafast
      x-ray computed tomography.
AB  - The objective was to validate the measurement of myocardial perfusion in humans
      by ultrafast computed tomography (CT), by comparing measurements with those from
      single photon emission computed tomography (SPECT). Measurement of myocardial
      perfusion with high spatial resolution (including the differentiation of
      subendocardial and subepicardial perfusion) may be possible by ultrafast CT in
      humans. Although there are encouraging data from experiments with dogs, the
      technique has not been validated in humans. In 11 patients, ultrafast CT
      measurement of regional perfusion in a single short-axis slice was compared with
      that obtained by SPECT, and in 14, reproducibility of ultrafast CT was evaluated.
      The ultrafast CT scanner was set to acquire 20 images, gated to end-diastole. The
      images were divided into 32 equal segments, and the time course and extent of
      opacification of the left ventricular cavity and myocardium were analyzed to
      calculate absolute perfusion. The thallium tomograms were also divided into 32
      segments for comparison. The pattern of relative perfusion by segment was
      represented as a curve. In 18 of 22 paired scans, the mean difference of the
      position of the minimum and maximum points of the curves was less than 4,
      indicating close agreement between the two techniques. When scoring segmental
      perfusion as normal or abnormal, there was agreement between the methods in 129
      of 176 segments ([symbol: see text] 0.41). Reproducibility (mean difference +/- 1
      SD) of basal scans was 0.005 +/- 0.2 mL/min/mL, and during adenosine vasodilation
      was 0.05 +/- 0.32 mL/min/mL. Absolute perfusion (mean +/- 1 SD) at rest was 0.52
      +/- 0.21 mL/min/mL. During adenosine infusion, perfusion increased to a mean of
      0.84 +/- 0.42 mL/min/mL. Ultrafast CT and intravenous contrast can be used to
      assess relative myocardial perfusion in humans, at rest and during adenosine
      vasodilatation, although it may underestimate absolute perfusion, particularly at
      high flow.

PMID- 8130604
TI  - Quantification of myocardial perfusion: the Holy Grail of cardiac imaging
      techniques?

PMID- 8130605
TI  - Positron emission tomography to quantitate myocardial perfusion.
AB  - The evolution of positron emission tomographic imaging devices coupled with the
      flexibility to easily label compounds with positron emitting radionuclides has
      enabled the development of quantitative methods for the noninvasive measurement
      of regional myocardial perfusion. The current state-of-the-art measurement
      methods are based on the kinetic characteristics of compounds that behave as
      inert, freely diffusible tracers or compounds that mimic the behavior of
      radiolabeled microspheres. Each of these myocardial blood flow methods has been
      developed so that the influence of resolution distortions in the finite
      resolution images is minimized. It is anticipated that the clinical extension of
      these myocardial blood flow methods will enable the noninvasive evaluation of
      coronary reserve, the assessment of the functional capacity of collateral
      circulation, and the effectiveness of treatment strategies for coronary artery
      disease. In this article, these methods are described and the initial
      experimental studies using these methods are summarized.

PMID- 8130607
TI  - A fast computed tomographic imaging method for myocardial perfusion.
AB  - Fast x-ray computed tomography can be used to generate indicator dilution curves
      in perfused tissues following intravascular injection of roentgen contrast agent.
      These curves can be used to estimate regional parenchymal perfusion,
      intravascular blood volume, heterogeneity of these two parameters, and vascular
      bed transfer function.

PMID- 8130608
TI  - Measurement of myocardial perfusion by fast computed tomography.

PMID- 8130609
TI  - Quantifying myocardial blood flow with contrast echocardiography.
AB  - The principal focus of this article has been to discuss the issues relating to
      the quantitation of myocardial perfusion using MCE. In its current form, this
      technique can provide important physiological information in the cardiac
      catheterization laboratory and the operating room as well as in the experimental
      laboratory. Standardization of echo contrast agents, echo equipment, and
      algorithms for image analysis will make it a truly quantitative technique in the
      near future. MCE has the potential to offer the unique opportunity of
      simultaneously assessing regional myocardial flow and function in various
      ischemic syndromes.

PMID- 8130610
TI  - Regional uptake of [123I]-16-iodo3-R,S-methyl hexadecanoic acid in patients with
      myocardial infarction. Comparison with thallium 201 uptake and wall motion.
AB  - Thirty patients with recent myocardial infarction were intravenously injected
      with the modified fatty acid [123I]16-iodo-3R,S-methyl hexadecanoic acid (MIHA)
      at peak exercise to quantify viable myocardium after infarction. The results were
      analysed visually and quantitatively and compared with those obtained after
      injection of thallium 201 at peak exercise with single-photon emission computed
      tomography (SPECT) imaging immediately and 4 hours later. Ventriculography was
      used to study regional wall motion in all patients. In the visual comparison of
      201Tl- and MIHA-SPECT scintigrams, 98.8% of normal segments (N) and 96% of
      temporary thallium-defect segments (T) were N or T on MIHA-SPECT scintigrams
      (91.3% and 70.5%, respectively, in the quantitative analyses). In contrast, 47.2%
      of permanent thallium-defect segments (P) were N or T on the MIHA-SPECT
      scintigrams (20.6% in the quantitative analysis). Revascularization therapy could
      only be recommended on the basis of MIHA-SPECTs in 5 to 8 of the 30 patients. To
      confirm the superiority of MIHA over 201Tl to evaluate myocardial viability, one
      must compare their uptake with myocardial contractility after revascularization.

PMID- 8130611
TI  - Diagnostic approaches for detecting deep vein thrombosis.
AB  - Acute deep vein thrombosis remains a disease for which the diagnosis must be
      confirmed by an objective testing procedure. The current methods in use include
      continuous-wave Doppler, impedance plethysmography, and ultrasonic duplex
      scanning. The Doppler and plethysmographic methods are of value for the detection
      of proximal venous occlusion but do have limitations below the knee and fail to
      provide specific information concerning the exact location and extent of
      involvement. Duplex scanning, which has both imaging and flow detection
      capabilities, can be used from the level of the inferior vena cava to below the
      knee. When duplex scanning is used, the following variables are used in arriving
      at a diagnosis: visualization of the thrombus, lack of compressibility of the
      vein, and the absence of spontaneous and phasic flow from the large veins. When
      all of these variables are used in the screening process, the sensitivity and
      specificity will be in the range of 90% to 100%. Most false-positive results
      occur when the incompressibility variable is attempted for the iliac veins and
      the superficial femoral vein in the adductor canal. The majority of false
      negatives will be related to missed thrombi in the small veins of the calf.

PMID- 8130612
TI  - Cardiac structure and function in chronic thromboembolic pulmonary hypertension.
AB  - The observations made on patients with chronic TE-PH conform with the work of
      others who have shown marked right-sided cardiac chamber enlargement and abnormal
      left-sided diastolic function in patients with other forms of PH and RV pressure
      overload. The unique results from our patient population are a consequence of the
      reversal of these structural and functional abnormalities early after surgical
      treatment of the PH. The reversal of these abnormalities, including normalization
      of RV function, is extremely important when considering forms of therapy such as
      isolated lung transplantation, where a failure of RV function to normalize would
      be catastrophic. Although echocardiography is currently limited by its data
      acquisition in two dimensions, the results concerning measurements of area and
      length, rather than volume, are convincing. It is anticipated that future
      application with techniques such as three-dimensional reconstruction of
      echocardiographic images will allow an even more thorough evaluation of the
      cardiac structural and functional changes in patients with thromboembolic
      pulmonary hypertension.

PMID- 8130613
TI  - Echocardiographic diagnosis of paradoxical embolism and the potential for right
      to left shunting.
AB  - Echocardiographic techniques are useful in establishing the presumptive clinical
      diagnosis of paradoxical embolism. Once a clinical diagnosis of systemic embolism
      has been established and a potential systemic venous source for embolic material
      has been diagnosed, echocardiographic (and particularly transesophageal
      echocardiographic techniques) can readily establish the presence or absence of an
      intracardiac communication and can help define the potential for right to left
      shunting across that communication (using saline contrast techniques). Except for
      the rare circumstance where echocardiography has been used to actually image
      paradoxical embolization in progress (such as may occur during intraoperative
      monitoring), the technique can only show the potential for such a mechanism for
      systemic embolization. Because patency of the foramen ovale is a common anatomic
      variant (occurring in approximately 25% of subjects) and transesophageal contrast
      echocardiography will show at least transient right to left shunting in most
      patients with patent foramen ovale, a mechanistic relationship between such
      findings and the occurrence of a systemic embolic event cannot be immediately
      inferred. Clinical assessment of alternative mechanisms for systemic embolization
      is required to judge the likelihood that the potential for paradoxical
      embolization is, in fact, the cause for systemic embolism in a given patient.

PMID- 8130614
TI  - Atrial septal aneurysm as a potential source of neurological ischemic events.
AB  - An atrial septal aneurysm (ASA) is a congenital malformation of the atrial septum
      characterized by bulging of the septum overlying the fossa ovalis region into
      either atrium. The prevalence of ASA varies according to the diagnostic method
      used and to the type of population studied. A practical classification of ASA
      based on the current knowledge of its pathogenesis into Type I, Type II, and Type
      III is presented. With the widespread use of transesophageal echocardiography in
      recent years, ASA has become an increasingly recognized entity. Recently, the
      clinical interest in ASA has been increased by several reports in the literature
      proposing ASA as a potential source of emboli. The three most plausible
      mechanisms to link this association are thrombus formation in or around the ASA,
      paradoxical embolization through an interatrial communication in the form of
      patent foramen ovale or atrial septal defect, and mitral valve prolapse that has
      been found to be frequently associated with ASA. Although the echocardiographic
      detection of ASA is in most cases an incidental finding, the identification of
      ASA should prompt careful review of the echocardiogram for mitral valve prolapse,
      atrial septal defect, and patent foramen ovale. Although conclusive evidence of a
      causal relation between ASA and cerebrovascular emboli has not been shown, the
      identification of ASA in such patients in the absence of another cause to explain
      the embolic event may represent an indication for long-term antiplatelet or
      anticoagulation therapy, or even surgery. Until long-term follow-up results of
      these patients are available, management should be on an individual basis.

PMID- 8130615
TI  - Transthoracic and transesophageal echocardiography for the evaluation of cardiac
      tumors, thrombi, and valvular vegetations.
AB  - Echocardiography is commonly used for the detection, assessment, and diagnosis of
      intracardiac masses. Since the introduction of M-Mode ultrasound in 1954, the
      subsequent development of two-dimensional Doppler, and transesophageal
      echocardiographic techniques have shown clinical efficacy in the evaluation of
      intracardiac pathology. The various presentations of cardiac tumors, thrombi, and
      valvular vegetations can pose a diagnostic challenge. In addition, once a
      diagnosis is established, data regarding risk stratification and prognosis are
      often required for further management. Echocardiography can serve these clinical
      needs.

PMID- 8130616
TI  - Spontaneous echocardiographic contrast.

PMID- 8130617
TI  - Detection of intracardiac masses by ultrafast computed tomography.
AB  - Ultrafast computed tomography (CT) is a new imaging technique that relies on
      electron beam technology. Its short scanning acquisition times eliminate the
      motion artifacts seen with conventional CT. High temporal and spatial resolution
      make it ideal for evaluating the heart using only modest amounts of intravenous
      contrast. Ultrafast CT is extremely valuable for diagnosis and assessment of
      intracardiac thrombus and cardiac tumors. Although echocardiography is widely
      used to identify intracardiac thrombus, it sometimes cannot visualize the most
      common sites, the atria (especially the left atrial appendage) and the cardiac
      apex. These areas are clearly defined by ultrafast CT. Likewise, the location,
      size, extent, and tissue density of primary or metastatic cardiac tumors can be
      characterized using ultrafast CT, which may obviate the need for angiography
      before operative treatment.

PMID- 8130618
TI  - Diagnosis and characterization of intracardiac masses by magnetic resonance
      imaging.

PMID- 8130619
TI  - Cardiovascular imaging: new applications, new insights, and new choices in the
      diagnosis and treatment of vascular embolism.

PMID- 8130620
TI  - Imaging techniques for identifying left ventricular thrombi.

PMID- 8130621
TI  - The role for cardiac imaging in the evaluation of patients with stroke-
      perspectives of a neurologist: if there's smoke, is there fire?

PMID- 8130622
TI  - Patients for whom DRGs were not designed.

PMID- 8130623
TI  - Collective action on specialty education.

PMID- 8130624
TI  - CACCN National Standards Steering Committee update. Development of standards for
      critical care.

PMID- 8130625
TI  - The option of intensive care for the patient with AIDS (a literature review).
AB  - The utilisation of intensive care facilities in the treatment of Acquired
      Immunodeficiency Syndrome (AIDS) related disease has been traditionally
      questioned on the basis of early results of poor prognosis for patients with AIDS
      admitted to Intensive Care Units (ICUs). However, recent reviewers have pointed
      out a significant improvement in in-hospital survival rates for AIDS patients
      admitted to ICU. Improved prognosis may be related to improved drug therapies in
      response to Pneumocystis Carinii Pneumonia (PCP) infection (including the use of
      corticosteroids), as well as initiating mechanical ventilation in response to the
      associated respiratory failure earlier in the disease process. The decision to
      utilise intensive care facilities is often complicated by AIDS related
      neurological complications, rendering the patient incapable of consenting to (or
      refusing) treatment. The importance of obtaining a Human Immunodeficiency Virus
      (HIV) infected patient's wishes in regard to their long term management is
      discussed. Options that have been used previously by patients with AIDS to ensure
      such wishes are carried out are presented.

PMID- 8130626
TI  - A fully automated HPLC method for the determination of catecholamines in
      biological samples utilizing ethylenediamine condensation and peroxyoxalate
      chemiluminescence detection.
AB  - A fully automated in-line extraction reversed-phase high-performance liquid
      chromatography (HPLC) method with chemiluminescence detection was developed for
      the analysis of human and rat plasma catecholamines (CAs), norepinephrine (NE),
      epinephrine (E) and dopamine (DA). N-Methyldopamine (N-MeDA) was used as an
      internal standard. The method involves collection of plasma samples, which are
      first diluted with a sample dilution buffer containing N-MeDA, and in-line
      extraction of CAs using a carboxylic acid small resin precolumn (SERUMOUT-CEX).
      This pre-extraction process was coupled with an HPLC system including reversed
      phase mode separation on an analytical column (TSK gel ODS-80Ts), fluorogenic
      derivatization with ethylenediamine (ED) and finally postcolumn peroxyoxalate
      chemiluminescence reaction detection using bis [4-nitro-2-(3,6,9
      trioxadecyloxycarbonyl)phenyl]oxalate (TDPO) and hydrogen peroxide. The optimized
      mobile phase compositions, flow rates, operation timing for the adsorption and
      desorption of CAs in the precolumn, the separation in the analytical column and
      the optimum fluorogenic and chemiluminogenic reaction conditions were
      investigated. The detection limit for all the CAs was about 1 fmol (signal-to
      noise ratio is 2). Excellent linearity of the calibration curves for CAs was
      observed in the range from 5 to 500 fmol for each CA using the internal standard.
      The relative standard deviations of the method for determining NE (183 fmol), E
      (23.6 fmol) and DA (6.1 fmol) in 50 microL of human plasma (n = 3) were 2.8, 2.7
      and 3.1%, respectively, for the within-day assay and 5.0, 3.8 and 4.0%,
      respectively, for the between-day assay. The method was applicable to the
      determination of CAs in 25-50 microL of human or rat plasma.

PMID- 8130627
TI  - Relations between blood pressure and plasma norepinephrine concentrations after
      administration of diltiazem to rats: HPLC-peroxyoxalate chemiluminescence
      determination on an individual basis.
AB  - A calcium antagonist, diltiazem, was infused continuously into Sprague-Dawley
      rats through the left femoral vein at four different flow rates. The mean
      arterial blood pressure and concentrations of plasma norepinephrine (NE) were
      measured in each single rat (n = 5) and the correlations between them were
      studied. Blood (150 microL) was collected 13 times during the infusion. Plasma NE
      was determined by HPLC-ethylenediamine condensation reaction-peroxyoxalate
      chemiluminescence detection system (HPLC-ED-PO-CL). In four cases from 5 rats,
      the blood pressure reduction caused by diltiazem was inversely correlated to
      logarithm of plasma NE concentration. The relation was expressed as Y = -alogX+m.
      The coefficients of correlation were -0.9506, -0.9293, -0.9341 and -0.8675,
      respectively. The correlation for the last rat was worse (r = -0.0799). The good
      correlation would imply that the sympathetic nervous system released NE to
      maintain blood pressure up to the normal level, responding to the sympathetic
      nervous system released NE to maintain blood pressure up to the normal level,
      responding to the blood pressure reduction caused by diltiazem. The present
      experiment proved the feasibility of the determination method of NE utilizing
      HPLC-ED-PO-CL detection in applying to the individual rats.

PMID- 8130628
TI  - Direct enantioselective separation of bevantolol by high-performance liquid
      chromatography on normal and reverse cellulose chiral stationary phases.
AB  - A direct, isocratic and simple chromatographic method is described for the
      enantiomeric separation of bevantolol (BEV) using normal and reverse cellulose
      tris (3,5-dimethylphenylcarbamate) chiral stationary phases (CSPs) known as
      Chiralcel OD and Chiralcel OD-R, respectively. The effect of various alcohols
      present in the mobile phase on the separation factor (a) and resolution factor
      (Rs) has been studied. The method has been used to determine and identify the BEV
      enantiomers in human urine after oral administration of racemic BEV. The chiral
      recognition mechanism(s) between the analyte and these chiral stationary phases
      is proposed.

PMID- 8130629
TI  - Rapid assay of iopanoic acid in dog plasma using a Hisep column.
AB  - A rapid method for the determination of iopanoic acid (IOP) in dog plasma
      utilizing a Hisep column was developed. A mobile phase of 12% methanol, 88% 0.05
      M phosphate buffer pH 3.4 yielded a k' of 8.5 with no interference from proteins
      present in plasma. Recoveries of IOP from spiked plasma ranged from 97% to 103%
      at 270 mumol/L and 1.75 mmol/L respectively. Replication was +/- 2.8% at 1.75
      mmol/L and +/- 6% at 21 mumol/L. A method utilizing 2,4,6-triiodobenzoic acid as
      internal standard was also developed for comparison.

PMID- 8130630
TI  - A liquid chromatographic method for the determination of fenoprofen in equine
      plasma and urine.
AB  - A high performance liquid chromatographic method to measure plasma and urine
      fenoprofen levels in equine biofluids is described. Liquid-liquid extraction with
      diethylether was used to isolate the drug from plasma and urine. The accuracy and
      reproducibility of the method were within acceptable limits over the
      concentration range 0-10 micrograms/mL and 0-20 micrograms/mL respectively from
      plasma and urine. Detection limits were 0.05 microgram/mL (2 mL plasma) and 0.2
      microgram/mL (0.5 mL urine). This procedure was applied to ascertain the
      pharmacokinetics of a 3 g dose of fenoprofen calcium in a horse.

PMID- 8130631
TI  - Experimental models for optimization of insulin separation on reversed phase
      columns.
AB  - Experimentally defined relationships have been found to describe adequately the
      retention and separation of bovine and porcine insulins as well as their desamido
      products on reversed phases C4 30 nm and C18 10 nm pore diameter. The equations
      are valid for a region of initial acetonitrile concentrations from 16 to 31% and
      gradient rates from 0.04 to 0.60%/min. The peak heights showed an exact non
      linear relationship with the time interval between the first and last peak of
      interest, independent of their retention time. The number of experiments required
      for obtaining the parametric estimates of the models depends on the particular
      task, but in all cases is less than eight. The relationships found permit the
      correct choice to be made in advance both for analysis conditions for a
      particular column and for different requirements of insulin analysis.

PMID- 8130632
TI  - Direct determination of mitoxantrone in plasma by high performance liquid
      chromatography using an automatic precolumn-switching system as sample clean-up
      procedure.
AB  - A high-performance liquid chromatography method which uses direct injection and a
      column-switching valve for determination of mitoxantrone in plasma is described.
      After addition of internal standard, plasma was deproteinized by adding 5
      sulphosalicylic acid reagent. The supernatant was injected onto an enrichment
      precolumn flushed with washing solvent (methanol and water 5:95). Absorbed
      mitoxantrone was backflushed from the precolumn into an analytical column C18
      Nucleosil 250 x 4 mm with a gradient elution (solvent A, ammonium formate buffer
      1.6 M, pH 4.3; solvent B, acetonitrile and water 40:60; linear gradient from 45
      to 55% of B for 30 min was programmed) at a flow rate of 1.3 mL/min. Detection
      was carried out at 665 nm. This method showed obvious advantages over
      conventional extraction procedures in terms of speed and facility of sample
      handling.

PMID- 8130633
TI  - High performance liquid chromatographic determination of methacrylate in blood
      serum.
AB  - Methacrylic acid is a hydrolytic breakdown product of methylmethacrylate which is
      widely used in orthopaedic surgery, dentistry and in the chemical industry for
      fabrication of acrylic resins. Information on the toxicity of methacrylic acid
      and its metabolism is limited. To facilitate studies in this field we developed a
      liquid chromatographic procedure allowing determination of methacrylate in blood
      serum. The procedure was based on reversed-phase HPLC using a gradient elution
      with UV detection at 210 or 240 nm. The method was linear up to 5 mM
      concentration with a detection limit of 0.5 microM. The procedure was applied to
      determination of methacrylate in rat blood serum after administration of sodium
      methacrylate solution into the stomach. A peak of this compound was demonstrated
      in the chromatogram 10 min after administration which disappeared after 60 min,
      confirming suitability of the method for biological applications.

PMID- 8130634
TI  - Charge-transfer chromatographic study on the interaction of amino acids with
      ethoxylated stearic acid surfactants.
AB  - The interaction of amino acids with ethoxylated stearic acid nonionic surfactants
      was studied by charge-transfer reversed-phase thin-layer chromatography and the
      relative strength of interaction was calculated. In the majority of cases the
      surfactant has a negligible effect on the hydrophobicity of amino acids. Only the
      binding of Asn, Cys, Gln, Leu, Lys, Met, Nle, Phe, Ser, Trp and Tyr to the
      surfactants was observed, however, the strength of interaction was fairly low.
      Stepwise regression analysis proved that the electronic parameters of the amino
      acids have the highest impact on the strength of interaction. This finding
      supports the hypothesis that the binding of ethoxylated stearic acid nonionic
      surfactants to proteins involves more than one amino acid residues and that the
      hydrophilic forces have a considerable impact on the interaction.

PMID- 8130635
TI  - Sensitive determination of (-)-isoproterenol and (-)-(R)-1-(3,4- dihydroxyphenyl)
      2-[(3,4-dimethoxyphenethyl)amino] ethanol (T-0509), a cardiotonic agent, in rat
      plasma utilizing a fully automated catecholamine analyser.
AB  - (-)-Isoproterenol (ISO), used as bronchodilator, and (-)-(R)-1-(3,4
      dihydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (T-0509), a new
      cardiotonic agent, were determined in rat plasma (only 25 microL) using a fully
      automated catecholamine (CA) analyser that includes in-line pre-extraction of
      CAs, coupled with an HPLC-ethylenediamine condensation reaction and a
      peroxyoxalate chemiluminescence detection system (HPLC-ED-PO-CL). The
      chromatographic conditions were: precolumn, SERUMOUT-CEX; buffer for delivering
      CAs in the precolumn, 10 mM potassium phosphate buffer (pH 7.5)/ethanol (92 + 8,
      v/v) (1 mL/min); precolumn clean-up solution, 4% phosphoric acid/acetonitrile (50
      + 50, v/v) (1 mL/min); analytical column, TSKgel ODS-80Ts, 250 x 4.6 mm i.d.;
      eluent, 75 mM potassium acetate buffer (pH 3.2)/50 mM potassium phosphate buffer
      (pH 3.2)/acetonitrile (83.6 + 4.4 + 12, v/v/v for ISO and 76 + 4 + 20 v/v/v for T
      0509) (1 mL/min); fluorogenic reagent solution, 105 mM ED and 175 mM imidazole in
      acetonitrile/ethanol (90 + 10, v/v) (0.25 mL/min); chemiluminogenic reaction
      solution, 0.25 mM TDPO, 150 mM hydrogen peroxide and 110 mM TFA in dioxane/ethyl
      acetate (50 + 50, v/v) (1.4 mL/min). Colterol, (+/-)-1-(3,4-dihydroxyphenyl)-2
      [(1,1-dimethyl)ethylamino]ethanol, (+/-)-N-t-butylnorepinephrine was used as an
      internal standard (IS) for ISO, and (+/-)-1-(3,4-dihydroxyphenyl)-2-[(3,4,5-
      trimethoxyphenethyl)amino]ethanol, (+/-)-(3,4,5-trimethoxyphenethyl- aminomethyl)
      3,4-dihydroxybenzylalcohol (T-1583) for T-0509. The detection limits for ISO and
      T-0509 were 1.3 and 0.9 fmol on injection, respectively.

PMID- 8130636
TI  - A note on chromatographic analysis of enantiomers by indirect method.

PMID- 8130637
TI  - Correlation of nucleotide base and sugar protons in a 15N-labeled HIV-1 RNA
      oligonucleotide by 1H-15N HSQC experiments.
AB  - The advent of methods for preparing 15N- and 13C-labeled RNA oligonucleotides
      holds promise for extending the size of RNA molecules that can be studied by NMR
      spectroscopy. A practical limitation is the expense of the 13C label. It may
      therefore sometimes be desirable to prepare a relatively inexpensive 15N-labeled
      sample only. Here we show that the two-bond 1H-15N HSQC experiment can be used on
      15N-labeled RNA to correlate the intranucleotide H1' and H8,H6,H5 resonances
      indirectly through the shared glycosidic nitrogen. The nonrefocused version of a
      standard HSQC experiment for 2D proton-detected 1H-15N chemical-shift correlation
      is applied in order to minimize the sensitivity loss due to the relatively fast
      spin-spin relaxation of RN oligonucleotides. The experiment is applied to the 30
      nucleotide RNA RBE3 which contains the high-affinity binding site of the RRE (rev
      response element) for the Rev protein of HIV. The results indicate that this
      simple experiment allows a straightforward identification of the base proton
      resonances CH5, CH6, UH5, UH6, purine H8, and AH2 as well as the intranucleotide
      H1' and H8,H6,H5 connectivities. When combined with a NOESY experiment, complete
      sequential assignments can be obtained.

PMID- 8130638
TI  - A new 2D NMR method for measurement of JHH coupling constants.
AB  - A new 2D NMR pulse sequence for E.COSY-type measurement of J(HH) coupling
      constants is introduced. It exploits a heteronuclear spin, e.g., 13C, for
      displacement in the omega(1) frequency dimension via a large heteronuclear J
      coupling. The experiment is demonstrated by application to a heptapeptide at the
      natural abundance 13C level. It is suitable, for example, for measurement of
      3J(HH) and 4J(HH) coupling constants in peptides and proteins.

PMID- 8130639
TI  - Unusual conformation of a 3'-thioformacetal linkage in a DNA duplex.
AB  - The DNA.DNA duplex d(CGCGTTSCH2OTTGCGC).d(GCGCAAAACGCG) (designated duplex III)
      containing a 3'-thioformacetal (3'-TFMA) linkage in the center of the sequence
      was characterized in detail by two- and three-dimensional homonuclear NMR
      spectroscopy. The NMR results were analyzed and compared with those of two
      duplexes of the same sequence: One is an unmodified reference sequence and the
      other contains a formacetal (OCH2O) linkage at the central T--T step (designated
      duplex I and duplex II, respectively). In general, the NMR spectra of duplex III
      closely resemble those of the analogous duplexes I and II, suggesting an overall
      B-type structure adopted by the 3'-TFMA-modified duplex III. Nonetheless, the
      detection of several distinct spectral features originating from the protons at
      the T6(3'-SCH2O)T7 modification site is indicative of a local conformation that
      is clearly different from the corresponding region in duplexes I and II. The 3'
      thioformacetal linker, in contrast to the formacetal (FMA) linkage, cannot be
      accommodated in a conformation usually found in natural nucleic acid duplexes. As
      a consequence, the 3'-TFMA-modified T6 sugar adopts an O4'-endo form (an
      intermediate structure between the usual C2'-endo and C3'-endo forms). This
      change is accompanied by a change in the epsilon (C4'-C3'-S3'-CH2) dihedral angle
      and by subsequent adjustments of other torsion angles along the backbone.
      Notably, this conformational readjustment at the T6-T7 backbone linkage is
      localized; its collective result has negligible effect on base-base stacking of
      the T6 and T7 residues. A close examination of the COSY data in all three
      duplexes reveals a subtle variation in sugar geometry, with more S-type character
      adopted by the modified duplexes II and III. The results of this study illustrate
      that, although the difference between FMA and 3'-TFMA linkages is merely in the
      substitution of the T6(O3') in the former by a sulfur atom in the latter, the
      stereoelectronic difference in a single atom can induce significant local
      structural distortion in an otherwise well-structured oligonucleotide duplex.

PMID- 8130640
TI  - Application of neural networks to automated assignment of NMR spectra of
      proteins.
AB  - Simulated neural networks are described which aid the assignment of protein NMR
      spectra. A network trained to recognize amino acid type from TOCSY data was
      trained on 148 assigned spin systems from E. coli acyl carrier proteins (ACPs)
      and tested on spin systems from spinach ACP, which has a 37% sequence homology
      with E. coli ACP and a similar secondary structure. The output unit corresponding
      to the correct amino acid is one of the four most activated units in 83% of the
      spin systems tested. The utility of this information is illustrated by a second
      network which uses a constraint satisfaction algorithm to find the best fit of
      the spin systems to the amino acid sequence. Application to a stretch of 20 amino
      acids in spinach ACP results in 75% correct sequential assignment. Since the
      output of the amino acid type identification network can be coupled with a
      variety of sequential assignment strategies, the approach offers substantial
      potential for expediting assignment of protein NMR spectra.

PMID- 8130641
TI  - The 13C chemical shifts of amino acids in aqueous solution containing organic
      solvents: application to the secondary structure characterization of peptides in
      aqueous trifluoroethanol solution.
AB  - The 13C chemical shifts for all of the protonated carbons of the 20 common amino
      acid residues in the protected linear pentapeptide Gly-Gly-X-Gly-Gly have been
      obtained in water at low pH as well as in aqueous solution containing 10, 20 and
      30% acetonitrile or trifluoroethanol. Dioxane was used as an internal reference
      and its carbon chemical shift value was found to be 66.6 ppm relative to external
      TMS in water. Comparison of the different referencing methods for 13C chemical
      shifts in organic cosolvent mixtures showed that an external standard (either TMS
      or TSP capillary) was the most appropriate. In the present study, external TSP
      was chosen to define the 0 ppm of the 13C chemical shift scale. When the
      difference in referencing the dioxane carbon resonance is taken into account, the
      carbon chemical shift values of the amino acids in aqueous solution are similar
      to those previously reported (Richarz and Wuthrich (1978) Biopolymers, 17, 2133
      2141; Howarth and Lilley (1979) Prog. NMR Spectrose., 12, 1-40). The
      pentapeptides studied were assumed to be in a random coil conformation and the
      measured 13C chemical shifts were used as reference values to correlate carbon
      chemical shifts with the secondary structure of two well-characterized peptides,
      bombesin and the 1-29 amino acid fragment of Nle27 human growth hormone-releasing
      factor. In both cases, the C alpha chemical shifts exhibited a characteristic
      positive deviation from the random coil values, which indicates the presence of
      alpha-helices.

PMID- 8130642
TI  - Fibril assembly and carotenoid overaccumulation in chromoplasts: a model for
      supramolecular lipoprotein structures.
AB  - Chromoplast development in ripening bell pepper fruits is characterized by a
      massive synthesis of carotenoid pigments, resulting in their distinctive red
      color. We have shown that 95% of these pigments accumulate in chromoplasts in
      specific lipoprotein fibrils. In addition to carotenoids, purified fibrils
      contain galactolipids, phospholipids, and a single, 32-kD protein, designated
      fibrillin, which has antigenically related counterparts in other species. Fibrils
      were reconstituted in vitro when purified fibrillin was combined with carotenoids
      and polar lipids in the same stoichiometric ratio found in fibrils in vivo.
      Antibodies directed against fibrillin were used to isolate a fibrillin cDNA clone
      and, in immunological studies, to follow its accumulation during the chloroplast
      to-chromoplast transition under different conditions. A model for fibril
      architecture is proposed wherein carotenoids accumulate in the center of the
      fibrils and are surrounded by a layer of polar lipids, which in turn are
      surrounded by an outer layer of fibrillin. Topological analysis of purified
      fibrils verified this structure. Collectively, these results suggest that the
      process of fibril self-assembly in chromoplasts is an example of a general
      phenomenon shared among cells that target excess membrane lipids into deposit
      structures to avoid their destabilizing or toxic effects. In addition, we have
      shown that abscisic acid stimulates this phenomenon in chromoplasts, whereas
      gibberellic acid and auxin delay it.

PMID- 8130643
TI  - A FUSCA gene of Arabidopsis encodes a novel protein essential for plant
      development.
AB  - Arabidopsis fusca mutants display striking purple coloration due to anthocyanin
      accumulation in their cotyledons. We describe six recessive fusca mutants
      isolated from Agrobacterium-transformed Arabidopsis families. These mutants first
      become defective during embryogenesis and exhibit limited seedling development.
      Double mutant constructs revealed that developmental defects were not simply a
      consequence of anthocyanin accumulation. fusca seedlings showed altered responses
      to several environmental and endogenous factors. Allelism tests established that
      three fusca loci are represented by mutants previously described as defective in
      light-regulated responses. To study the molecular basis of the fusca phenotype,
      we cloned the FUS6 gene. FUS6 encodes a novel protein that is hydrophilic, alpha
      helical, and contains potential protein kinase C phosphorylation sites. The FUSCA
      proteins appear to act in a network of signal transduction pathways critical for
      plant development.

PMID- 8130645
TI  - Heat shock proteins and autoimmunity: a critical appraisal.
AB  - Various lines of evidence suggest a close relationship between heat shock
      proteins (hsp) and numerous autoimmune diseases. However, the common
      interpretation of hsp as antigens which provide a direct link between infection
      and autoimmunity appears insufficient. Rather, anti-hsp immune responses seem to
      represent physiological constituents of immune homeostasis. hsp are found in
      different sources, including infectious agents, nutriment and self, and the
      development of autoimmune disease seems to be related to an imbalanced
      presentation of hsp peptides to the immune system from these different sources.

PMID- 8130644
TI  - Envelope membrane proteins that interact with chloroplastic precursor proteins.
AB  - The post-translational transport of cytoplasmically synthesized precursor
      proteins into chloroplasts requires proteins in the envelope membranes. To
      identify some of these proteins, label transfer cross-linking was performed using
      precursor to the small subunit of ribulose-1,5-bisphosphate carboxylase (prSSU)
      that was blocked at an early stage of the transport process. Two envelope
      proteins were identified: an 86-kD protein and a 75-kD protein, both present in
      the outer membrane. Labeling of both proteins required prSSU and could not be
      accomplished with SSU lacking a transit peptide. Labeling of the 75-kD protein
      occurred only when low levels of ATP were present, whereas labeling of the 86-kD
      protein occurred in the absence of exogenous ATP. Although both labeled proteins
      were identified as proteins of the outer envelope membrane, the labeled form of
      the 75-kD protein could only be detected in fractions containing mixed envelope
      membranes. Based on these observations, we propose that prSSU first binds in an
      ATP-independent fashion to the 86-kD protein. The energy-requiring step is
      association with the 75-kD protein and assembly of a translocation contact site
      between the inner and outer membrane of the chloroplastic envelope.

PMID- 8130646
TI  - Pro: evidence for a primary lesion in the target organ in autoimmune disease.
AB  - Despite nearly 40 years of organ specific autoimmunity research, a question of
      whether the immune response in autoimmunity is due to dysregulation of the immune
      system or to a primary lesion in the target organ remains unresolved. Strength in
      the immune dysregulation argument, for which there has never been direct evidence
      in man, has largely derived from failure to identify a primary lesion to account
      for it. That is, until recently. Just as inflammation was considered a primary
      cause of disease until microbes were discovered, so autoimmunity was looked upon
      as a state of immune dysregulation until the equivalent of microbes were
      discovered. The microbe equivalents are viral particles, expressed on the surface
      of target organ cells under certain circumstances, and often encoded in the
      host's genome. These neo-antigens induce a protective, rather than aggressive
      immune response and account for the very singular target specificity observed,
      for example in the beta cell destruction of type 1 diabetes.

PMID- 8130647
TI  - Contra: evidence against a primary lesion in the target organ in autoimmune
      disease.
AB  - We discuss evidence suggesting that autoreactive T cell clones are components of
      the normal immune repertoire. Since these lymphocytes reach the brain only in the
      activated state, activation must take place outside of the target tissue. Within
      the brain, most of the autoimmune T cells undergo apoptosis rather than further
      proliferation.

PMID- 8130648
TI  - Differential cytokine profiles in peripheral blood lymphocyte supernatants and
      skin biopsies from patients with different forms of atopic dermatitis, psoriasis
      and normal individuals.
AB  - There is increasing evidence that the activation of a selected T helper cell
      population producing a Th2-related cytokine pattern with IL-4 and IL-5 but not IL
      2 and interferon-gamma (IFN-gamma) may be involved in the pathogenesis of IgE
      mediated atopic diseases and in particular of atopic dermatitis (AD). However,
      the existence of a 'nonatopic' (intrinsic) form of AD (NAD) with normal serum IgE
      levels, negative RAST tests, negative immediate type skin reactions towards
      environmental allergens and a negative patients and family history for IgE
      mediated allergies raised the question whether this form may be explained by a
      different T cell activation and cytokine pattern. In the present study we
      compared the distribution of peripheral blood leukocyte and lymphocyte
      subpopulations, their activation state and cytokine production in peripheral
      blood lymphocyte supernatants and skin biopsies of patients with AD (n = 19), NAD
      (n = 14), psoriasis (n = 6) and normal individuals (n = 13). A characteristic
      eosinophilia was present in AD and NAD but not in psoriasis and normal controls.
      The three patient groups showed significantly increased numbers of activated CD4+
      and CD8+ cells as measured by IL-2R and HLA-DR expression. Determination of
      spontaneously released IL-2, IL-4, IL-5 and IFN-gamma from peripheral blood
      lymphocytes demonstrated a Th2-related cytokine pattern with elevated levels for
      IL-4 and IL-5 in AD patients only. Increasingly enough, patients with NAD
      displayed high IL-5 but low IL-4 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130649
TI  - Metallothionein in platelets.
AB  - The zinc content in platelets from rabbits, humans and horses was determined, and
      the levels of zinc were found to be significantly higher (3 micrograms/10(10)
      cells) than those in other peripheral blood cells. About 70% of the zinc in the
      supernatants of platelet lysates could be detected. From the results of gel
      filtration analysis, the zinc in platelet lysates was found to be bound with a
      low-molecular-weight protein (MW 6,000-8,000) detected as metallothionein (MT) on
      the basis of antigenic properties determined by enzyme-linked immunoassay and
      immunoblotting analysis using monoclonal antibodies raised against rabbit and
      horse MTs produced by murine hybridoma cell lines. The concentrations of MTs in
      the platelet lysates were quantitatively determined, and the average values were
      30.5 +/- 3.7, 39.4 +/- 4.2 and 39.7 +/- 4.4 micrograms/10(10) cells for rabbit,
      human and horse platelets, respectively. The antibody against rabbit MT reacted
      not only with its homologous antigen but also with heterologous antigens, whereas
      the antibody against horse MT reacted only with its homologous antigen. The
      biological function of MTs in platelets is not yet understood, but it is possible
      that platelet MT serves to regulate the homeostasis of metals and/or to preserve
      metals indispensable for the activation of enzymes or cells. The present study
      demonstrated the presence of MT in platelets.

PMID- 8130650
TI  - Latex antigens induce IgE and eosinophils in mice.
AB  - Hypersensitivity to latex proteins has been reported with increasing frequency in
      recent years. Elevated levels of latex specific IgE have been detected in the
      majority of these patients. Severe anaphylaxis and death resulting from latex
      exposure has also been reported. Nevertheless, the immune mechanism of latex
      allergy is not fully understood. In this report, we describe a model of latex
      allergy developed in mice exposed to latex proteins. Animals exposed to latex
      proteins demonstrated enhanced levels of total IgE, peripheral blood and lung
      eosinophilia, and elevated levels of serum IL-4 and IL-5. mRNA transcripts of IL
      4 and IL-5, but not IFN-gamma, could be demonstrated in spleen lymphocytes.
      Antibodies to latex belonging to all IgG subclasses were detected in the sera of
      mice exposed to latex antigens. The histology of the lung showed non-necrotizing
      granulomas and extensive interstitial chronic inflammatory infiltrates,
      particularly around bronchioles and small blood vessels. Although this model of
      latex allergy demonstrates a heterogeneous immunological response, the CD4
      positive Th2 cell-mediated response predominated.

PMID- 8130651
TI  - Interleukin-6 production by draining lymph node cells following primary contact
      sensitisation of mice: relationship to the proliferative response.
AB  - Interleukin-6 (IL-6) production and proliferative responses by draining lymph
      node cells were studied in mice exposed topically to a series of chemicals.
      Chemicals with the capacity to induce sensitisation, but not non-sensitisers,
      promoted both IL-6 production and lymph node cell proliferation ex vivo. The
      responses exhibited similar kinetics, were dependent upon the dose of topically
      applied allergen, and correlated significantly. We demonstrate that the main
      source of IL-6 within draining lymph nodes is not proliferating T lymphocytes.
      The induction of a strong IL-6 response, and the relationship of this to cellular
      proliferation indicate that production of this cytokine within the lymph node is
      closely associated with the induction of contact sensitivity in mice.

PMID- 8130652
TI  - Effect of cetirizine on human eosinophil superoxide generation, eosinophil
      chemotaxis and eosinophil peroxidase in vitro.
AB  - Cetirizine, a potent H1-antagonist, has been reported to inhibit eosinophil
      migration into human skin. We, therefore, further evaluated the effect of
      cetirizine on eosinophil function, including superoxide anion generation,
      chemotaxis, and eosinophil peroxidase (EP) release. In allergic subjects,
      superoxide anion generation 60 min after platelet-activating factor (PAF)
      activation was inhibited by concentrations of cetirizine ranging from 0.01 to 1
      microgram/ml (2.612 x 10(-8) to 2.612 x 10(-6) M). No significant inhibition was
      observed in normal subjects. PAF (10(-6) M)-induced eosinophil chemotaxis was
      also inhibited by cetirizine. In allergic subjects, percent inhibitions were 47.5
      +/- 6.1% at 0.01 microgram/ml, 50.8 +/- 5.1% at 0.1 microgram/ml and 58.9 +/-
      6.4% at 1 microgram/ml of cetirizine. In allergic subjects, N-formyl-methionyl
      lencyl-phenylalanine induced eosinophil chemotaxis was inhibited by cetirizine,
      although EP release was not. These results suggest cetirizine has effects on
      eosinophils which can not be explained by H1-blockade alone.

PMID- 8130653
TI  - Differences in eosinophil migration into the lungs following inhaled antigen
      challenge of parasite-naive guinea pigs with genetically determined differences
      in responsiveness to a gastrointestinal nematode parasite.
AB  - Parasite-naive guinea pigs with genetically determined differences in
      responsiveness to infection with the gastrointestinal nematode parasite
      Trichostrongylus colubriformis were sensitised to ovalbumin and later challenged
      by exposure to an ovalbumin aerosol. The resultant cellular migration into the
      lungs was assessed by histological examination of the lungs and enumeration of
      cells in bronchoalveolar lavage fluid 24 h, 72 h and 7 days later. Compared with
      parasite-low-responder guinea pigs, there were approximately 10 times more
      eosinophils in lavage fluid from parasite-high-responder animals but similar
      numbers of neutrophils.

PMID- 8130654
TI  - Pro-carboxypeptidase R cleaves bradykinin following activation.
AB  - Arginine carboxypeptidase (CPR) is a labile enzyme present in human serum which
      is unrelated to carboxypeptidase N. In this study we demonstrate that CPR exists
      in a precursor form in plasma and can be converted to the active form by trypsin
      and presumable trypsin-like enzymes. The trypsin-generated active form can not
      only cleave a small synthetic substrate, hippuryl-L-arginine, but can remove
      terminal arginine from bradykinin.

PMID- 8130656
TI  - [1993 Proceedings report of the German Association for Oto-Rhino-Laryngology and
      Head and Neck Surgery. Part II meeting report. Munster, Westfalen, 22-27 May
      1993. Abstracts].

PMID- 8130655
TI  - Inhibitory effect of pemirolast, a novel antiallergic drug, on leukotriene C4 and
      granule protein release from human eosinophils.
AB  - To determine whether pemirolast, a new antiallergic drug, inhibits the activation
      of eosinophils, we investigated the effect of pemirolast on the release of
      leukotriene C4 (LTC4) and eosinophil cationic protein (ECP) from human
      eosinophils. Calcium ionophore A23187 caused both LTC4 and ECP release from human
      eosinophils, whereas PAF and FMLP induced only ECP release from the eosinophils.
      Pemirolast (10(-6) to 10(-3) M) inhibited A23187-induced LTC4 release from the
      eosinophils in a dose-dependent fashion with 77% inhibition at 10(-3) M.
      Pemirolast (10(-5) to 10(-3) M) inhibited A23187-induced ECP release from the
      eosinophils in a dose-dependent fashion with 42% inhibition at 10(-3) M.
      Pemirolast (10(-4) and 10(-3) M) also inhibited PAF-induced and FMLP-induced ECP
      release from the eosinophils. We conclude that pemirolast prevents the activation
      of human eosinophils to inhibit LTC4 and ECP release. These results suggest that
      pemirolast might be useful in controlling allergic diseases by inhibiting
      eosinophil activation.

PMID- 8130657
TI  - [The development of endoscopic laparoscopy].

PMID- 8130658
TI  - [Surgical gynecology today and tomorrow. Main topic of the 13th Academic Congress
      of German-Speaking Faculty of Gynecology and Obstetrics, Hannover, 16-19 May
      1993. 2: Hysterectomy, ambulatory surgery and laparoscopy].
AB  - It is shown how in gynaecologic oncology, proceeding from former standardized
      techniques, an individualized multimodal therapeutic concept has been developed.
      New aspects are introduced concerning diagnosis and treatment in the field of
      operative urogynaecology. The world-wide problem of performing poorly indicated
      hysterectomies is also addressed. Dynamic developments in the field of out
      patient surgery will become an increasing challenge in the near future,
      influencing obstetrics and gynaecology to an extent that cannot be present be
      foreseen for the middle and long range. The forced evolution of conventional and
      laser-assisted laparoscopic surgery resulted in a nowadays broad spectrum of
      laparoscopically practicable surgical interventions, which made, even if still
      questioned by some experts, the vaginally assisted laparoscopic hysterectomy
      possible.

PMID- 8130659
TI  - [Effect of psychological factors in pregnancy on development of the parent-child
      relationship. 1: Basic considerations on the course of pregnancy].
AB  - The impact of psychological factors of pregnancy on the development of the child
      are discussed in context with first results of a research project. Furthermore
      some psychological psychological aspects of the course of pregnancy are shown. As
      a method of prevention we suggest a special form of psychosocial care during
      pregnancy, which gives adequate room for rejected parts of the relationship and
      especially for the experience of rage and fear, which can then be integrated.

PMID- 8130660
TI  - Birth trauma: its effect on the urine continence mechanisms.
AB  - Birth trauma is the most important etiological factor in the genesis of stress
      urinary incontinence in women (SUI). There is a high incidence of SUI during
      pregnancy, and after delivery SUI persists in a small percentage of women (2-3%).
      Almost all studies on perineal muscle function reveal decreasing intravaginal
      pressures in the days after delivery which rarely return to predelivery levels. A
      few urodynamics studies have demonstrated reduced urethral closure pressures and
      functional length after vaginal delivery, but the importance of such findings in
      the genesis of SUI is controversial. Better consensus has been found when pelvic
      floor neurophysiology was carried out: there is electromyographic evidence of a
      denervation-reinnervation pattern in the striated urethral sphincter muscle and
      occasionally prolonged pudendal conduction times when the pudendal nerves are
      directly stimulated. Histomorphologic studies of the pelvic floor have
      demonstrated that, in some women, abnormal collagen types are responsible for
      vaginal prolapse and accompanying SUI. Finally, the great importance of perineal
      reeducation by electromyostimulation and biofeedback in patients with traumatic
      pelvic floor pathology may be emphasized, but the importance of its role in the
      prevention of late SUI development remains to be established by more prospective
      studies.

PMID- 8130661
TI  - [Ovarian cancer after hysterectomy].
AB  - Between 1978 and 1988 we treated 538 patients at our department because of
      ovarian cancer. Among them were 37 patients, who had undergone hysterectomy
      before. When ovarian cancer was diagnosed, 28/37 were already in stage III or IV
      according to the FIGO classification (75.7%). Theoretically in 37/538 (6.8%) of
      our patients ovarian cancer could have been prevented by prophylactic
      oophorectomy during the previous hysterectomy performed because of other reasons.
      Current possibilities of hormone replacement could facilitate such a decision in
      individual cases.

PMID- 8130662
TI  - [Noninvasive fetal pulse oximetry sub partu. Experiences with the Ohmeda Biox
      3700 and the Baxter Asat 1000 Pulse Oximeter].
AB  - In this study oxygen saturation was measured at the presenting part of the fetus
      during labour. We used two different reflectance sensors together with two
      different pulse oximeters. The Baxter Asat 100 displayed a 25% lower functional
      oxygen saturation of haemoglobin (SaO2) compared to the Ohmeda Biox 3700 pulse
      oximeter. The mean duration of application using the Ohmeda Biox 3700 together
      with an adapted finger sensor was 36 min (SD +/- 17 min), an effective
      measurement was achieved for 15 min (SD +/- 9 min). The mean duration of
      application using the Baxter Asat 100 together with a commercial Baxter reflex
      sensor was 88 min (SD +/- 96 min), an effective measurement was attained for 73
      min (SD +/- 77 min).

PMID- 8130663
TI  - [Paracelsus and gynecology. 500 years ago Theophrastus Bombastus von Hohenheim
      was born].
AB  - 500 years ago Theophrastus Bombastus von Hohenheim, called Paracelsus, was born
      near Einsiedeln, the famous place of pilgrimage in Switzerland. Two gynecologists
      who later on became well-known medicohistorians--Bernhard Aschner (born in
      Vienna) and Paul Diepgen (born in Aachen)--created the basis for a summary of the
      etiopathogenetic ideas and therapeutic experiences of Paracelsus in gynecology.
      One must be aware of the fact that, living in a period between the Middle Ages
      and modern times, the great physician was not always able to differentiate
      between metaphysics and physics, e.g. in regard to menstruation, pregnancy,
      birth, tumors or hysteria. The hostility of his opponents and those who envied
      him during his lifetime as well as in the centuries after his death seems to
      continue today in a lack of respect for the great physician's privacy.

PMID- 8130664
TI  - ["From the origin and development of the French disease" to "Major wound
      treatment". The work and contributions of Theophrastus Bombastus von Hohenheim,
      called Paracelsus, on the occasion of the 500th anniversary of his birth year].
AB  - On the occasion of Paracelsus's 500th anniversary his life and works are
      critically portrayed and appreciated. The present state of Paracelsian research
      in different fields of academic science is shown in the congress report 'Neue
      Wege der Paracelsus-Forschung'.

PMID- 8130665
TI  - [Recommendations for oral contraception . 10th Meeting of the "Zurich Discussion
      Group", April 1993].

PMID- 8130666
TI  - [GnRH analogs versus gestagens in therapy of endometriosis].

PMID- 8130667
TI  - [Pelviscopic therapy of endometriosis].

PMID- 8130668
TI  - [Current pathophysiology and therapy of endometriosis].

PMID- 8130669
TI  - Predicting family physicians' resources. From "manpower" to "person power".

PMID- 8130670
TI  - A result of myocardial infarction?

PMID- 8130671
TI  - Radiology rounds. Acromegaly.

PMID- 8130672
TI  - Dermacase. Irritative diaper dermatitis.

PMID- 8130673
TI  - Family practice in Ontario. How physician demographics affect practice patterns.
AB  - As the demographics of practising physicians change, especially as the number of
      women doctors in an area increases, it is important that those planning for the
      provision of medical care in the future understand the relationships between the
      demographics and changes in practice patterns.

PMID- 8130674
TI  - Obstetrical practice after a family medicine residency.
AB  - To determine factors influencing physicians to provide obstetrical care, a
      questionnaire was sent to all 149 graduates of the University of Western Ontario
      family medicine program from 1987 to 1991, inclusive. Few (37.1%) of the 105
      respondents still performed low-risk deliveries. Most frequently cited negative
      factors included interference with lifestyle, interruption of regular office
      routine, and insufficient training in obstetrics. Rural postal code, neonatal
      advanced life support training, and older age positively correlated with
      obstetrical practice. Ways in which residency training programs could address the
      alarming decrease in family practice obstetrics are discussed.

PMID- 8130675
TI  - Genograms. Practical tools for family physicians.
AB  - A genogram can help a physician integrate a patient's family information into the
      medical problem-solving process for better patient care. A genogram allows a
      physician to obtain medical and psychosocial information from a patient easily
      and, as a result, to have a better understanding of the context of the presenting
      symptoms.

PMID- 8130676
TI  - Fragile X syndrome.
AB  - Fragile X syndrome is the most common form of inherited mental retardation. Only
      recently has it been possible to detect all carriers and transmitters. We review
      the syndrome and discuss the pedigree of a large fragile X family. Family doctors
      should identify cases in their practices so genetic counseling can be offered to
      the families.

PMID- 8130677
TI  - Practical approaches to eating disorders in adolescence. Primer for family
      physicians.
AB  - Primary care physicians have an important role in assessing and managing
      adolescents who present with low weight. Initial diagnosis should be based on
      current understanding of adolescents' eating behaviours and be followed by
      obtaining supportive evidence. A practical developmental approach to management
      should be emphasized. Criteria for hospitalization, a three-step approach to
      management, and indications for expanding from a primary care to a team approach
      are discussed.

PMID- 8130678
TI  - Irritable bowel syndrome. Strategy for the family physician.
AB  - Irritable bowel syndrome is one of the most common reasons for disability and
      health care seeking. A sensible strategy for management incorporates a confident
      diagnosis based upon history, physical examination, and pertinent tests. The
      physician can then reassure the patient, offer dietary and stress management
      advice, and recommend bran to relieve constipation and to evoke the placebo
      response. Patients who do not respond could require supportive psychotherapy or a
      drug for the dominant symptom. A few require careful referral, but overall
      responsibility should remain with the primary physician.

PMID- 8130679
TI  - Spray bottle epicondylitis. Diagnosing and treating workers in pain.

PMID- 8130680
TI  - Condom double standard.

PMID- 8130681
TI  - Kick-starting a heterosexual epidemic.

PMID- 8130682
TI  - Haematological manifestations of systemic lupus erythematosus.
AB  - Haematological involvement is common in systemic lupus erythematosus (SLE).
      Whilst anaemia is most often due to chronic disease, other causes such as
      autoimmune haemolytic anaemia and hypoplastic anaemia need to be considered. The
      increased risk of infection in patients with SLE is due in part to changes in the
      white blood cells though treatments do not yet aim to modify these.
      Thrombocytopenia occurs frequently and is almost invariably autoimmune. It is
      often of little consequence, but may occasionally be severe and serious,
      requiring aggressive treatment. Patients with SLE have an increased risk of
      thrombosis, increased further in the presence of antiphospholipid antibodies
      (aPL). Changes in the haemostatic system and new insights into the nature of aPL
      are described.

PMID- 8130683
TI  - Empiric amphotericin B therapy: the need for a reappraisal.
AB  - Neutropenic patients are at high risk of developing invasive fungal diseases. A
      number of studies, both randomized and historical, have demonstrated that empiric
      therapy with amphotericin B in neutropenic patients with fever, refractory to
      antibiotics, results in a decrease in the frequency and mortality of deep fungal
      infections. Recent years have seen a number of advances in the management of
      neutropenic patients. Reasonably effective antifungal prophylaxis now exists and
      in many centres forms part of the routine care of neutropenic patients. Other
      centres advocate the use of selective decontamination and/or protective
      isolation. Furthermore the duration of neutropenia can be reduced with the use of
      haematopoetic growth factors. The impact of empiric amphotericin B in patients
      already benefiting from such treatments has not been adequately studied. The
      optimum dose of empiric amphotericin B is not defined. The criteria for
      commencing amphotericin B therapy in febrile neutropenic patients must therefore
      be redefined on the basis of further studies carried out in the context of these
      developments. We offer an approach to the use of empiric amphotericin B based on
      risk factors and prophylaxis.

PMID- 8130684
TI  - Epstein-Barr virus in lymphomas: a review.

PMID- 8130685
TI  - The rational administration of colloids.
AB  - The safe administration of i.v. fluids is one of the most significant advances in
      the care of critically ill patients this century. However, despite advances in
      the monitoring of cardiovascular variables, the questions of what? when? and how
      much? remain areas of enormous controversy. Ironically as the choice of i.v.
      fluids becomes greater and the monitoring more sophisticated the controversy
      grows. This article will concentrate on the diagnosis of hypovolaemia, the
      consequences of hypovolaemia and the rational use of i.v. fluids, particularly
      colloids, to treat it.

PMID- 8130686
TI  - Factor XIII: inherited and acquired deficiency.
AB  - Factor XIII (XIII), an enzyme found in plasma (present as a pro-enzyme),
      platelets and monocytes, is essential for normal haemostasis. It may also have a
      role to play in the processes of wound healing and tissue repair. Inherited XIII
      deficiency results in a life-long, severe bleeding diathesis which, if untreated,
      carries a very high risk of death in early life from intracranial bleeding. XIII
      is a zymogen requiring thrombin and calcium for activation. In plasma, XIII has
      two subunits: the 'a' subunit, which is the active enzyme, and the 'b' subunit
      which is a carrier protein. Activated XIII modifies the structure of clot by
      covalently crosslinking fibrin through an epsilon (gamma-glutamyl)lysine link. It
      also crosslinks other proteins, including fibronectin and alpha-2-plasmin
      inhibitor (alpha-2PI), into the clot through the same link. Clot modified by XIII
      is physically stronger, relatively more resistant to fibrinolysis and may be a
      more suitable medium for the ingrowth of fibroblasts. Inheritance of factor XIII
      is autosomal recessive. The majority of patients with the inherited defect show
      no XIII activity and absence of 'a' subunit protein in plasma, platelets and
      monocytes. At the molecular level, the defect is not a major gene rearrangement
      or deletion, but most likely a single point mutation which may be different in
      each family. Because of the severity of the bleeding diathesis, prophylaxis is
      desirable and has been shown to be very effective as the in vivo half-life of
      plasma XIII is long, and low plasma levels are sufficient for haemostasis.
      Acquired inhibitors have been reported in only two cases with inherited XIII
      deficiency. Acquired XIII deficiency has been described in a variety of diseases
      and bleeding has been controlled by therapy with large doses of XIII in such
      conditions as Henoch-Schonlein purpura, various forms of colitis, erosive
      gastritis and some forms of leukaemia. Large dose XIII therapy has also been used
      in an endeavour to promote wound healing after surgery and bone union in non
      healing fractures. The use of XIII in these conditions remains controversial.
      Very rarely a bleeding diathesis results from the development of a specific
      inhibitor to XIII arising de novo, often as a complication in the course of a
      disease or in association with long-term drug therapy. The bleeding diathesis in
      these patients is difficult to treat.

PMID- 8130687
TI  - Iron regulatory factor--the conductor of cellular iron regulation.
AB  - All cells have to adjust uptake, utilization and storage of iron according to the
      availability and their requirement for this essential metal. Progress in recent
      years has led to the elucidation of the molecular control mechanisms that co
      ordinate the uptake, utilization and storage of iron in mammalian cells and has
      highlighted the role of a newly-identified regulatory protein, the iron
      regulatory factor (IRF). IRF is a cytoplasmic protein that senses the
      intracellular iron level and responds by adjusting its function. When the iron
      level is low, it binds to so-called 'iron responsive elements' (IREs) contained
      in the mRNAs encoding proteins involved in iron metabolism and erythroid haem
      synthesis. When levels of cellular iron rise, IRF converts into the enzyme
      aconitase and looses its ability to bind to IREs. We discuss both functions of
      this Janus face protein and describe how its function is controlled by the status
      of an iron sulphur cluster in the IRF protein. We also speculate about how an IRF
      mediated regulation may relate to certain medical disorders.

PMID- 8130688
TI  - Typing of Neisseria gonorrhoeae by auxotype, serovar and lectin agglutination.
AB  - A total of 267 strains of Neisseria gonorrhoeae, comprising 129 serogroup IA and
      138 serogroup IB, isolated in Edinburgh over a two-year period were analysed to
      assess the discrimination given by three typing methods: auxotyping; serotyping
      using the Genetic Systems (GS) and Pharmacia (PH) monoclonal antibody panels; and
      lectin agglutination. Each typing system was assessed individually and in
      combination. Serotyping subdivided the strains into 14 GS and 18PH serovars.
      Auxotyping (Aux) yielded 11 separate auxotypes while lectin agglutination yielded
      22 different reaction patterns (LP). The standard auxotype/GS serovar (A/S)
      classification system yielded 37 classes. Lectin agglutination allowed further
      subdivision of the main A/S classes. AHU/IA-2 strains,which accounted for 70% of
      IA strains, yielded nine different lectin patterns (A/S/LP classes). Likewise,
      lectin agglutination allowed subdivision of the main IB A/S classes. NR/IB-1,
      NR/IB-2 and NR/IB-3, which accounted for 28%, 38% and 20% respectively of the IB
      strains, yielded 7, 7 and 6 A/S/LP classes respectively. It was concluded that
      lectin agglutination is a useful adjunct to the standard A/S classification
      system for studying the micro-epidemiology of gonococcal infection.

PMID- 8130689
TI  - Neisseria gonorrhoeae penicillin susceptibility: a comparison of three testing
      methods.
AB  - The 3-disc sensitivity method and the PDM Epsilometer (E-Test) were compared
      against the agar plate dilution reference method for the testing of N.
      gonorrhoeae penicillin susceptibility. Forty-six clinical isolates and five
      reference strains were examined. Both methods showed a high level of correlation
      in the detection of both high and moderate levels of resistance and both should
      be considered suitable for routine use. The E-Test had the advantage of producing
      a precise breakdown of the level of moderate resistance and may have a role to
      play in the diagnostic laboratory for this type of work.

PMID- 8130690
TI  - Mycoplasma pneumoniae infection: early diagnosis by detection of specific IgM by
      immunofluorescence.
AB  - An indirect immunofluorescent antibody test for early detection of IgM antibodies
      to Mycoplasma pneumoniae is described, using sera from which IgG antibodies have
      been removed. The results over a five-year period were studied and compared with
      complement fixation testing and isolation of the organism. During the epidemic
      season of November 1990 to April 1991, the immunofluorescent IgM test was used as
      a first-line test on specimens taken both early and late in the illness to
      provide a simple, inexpensive and clinically useful test, with 151 positive
      results being obtained from 886 sera tested.

PMID- 8130691
TI  - Nucleolar organiser regions in odontogenic cysts and ameloblastomas.
AB  - Silver nucleolar organiser region (AgNOR) counts were performed on apical
      periodontal cysts, dentigerous cysts, odontogenic keratocysts, ameloblastomas and
      basal cell carcinomas. Significant differences, but with excessive overlap, were
      shown between dentigerous cysts and apical periodontal cysts and between
      odontogenic keratocysts and apical cysts. The mean AgNOR counts for all
      odontogenic cysts ranged between 2.02 and 2.65, and for ameloblastomas were 2.24,
      indicating that the method has neither a diagnostic nor a prognostic value in
      these lesions. Control oral squamous cell carcinoma tissues had significantly
      higher AgNOR counts than any other lesion tested.

PMID- 8130692
TI  - Differential leucocyte analysis of samples up to 48 hours old: improved results
      with citrate pyridoxal phosphate anticoagulant.
AB  - Routine haematology screening, including differential leucocyte counts, were
      performed using a Coulter STKS analyser on blood samples taken into several
      commonly available anticoagulants at time intervals up to 48 h after
      venepuncture. An anticoagulant based on citrate phosphate dextrose adenine, with
      a platelet anti-aggregant/dis-aggregant pyridoxal-5-phosphate (CPP), was found to
      be superior to tri-potassium ethylene diamine tetra-acetic acid (K3EDTA) in its
      ability to preserve leucocytes for differential counting in the STKS analyser and
      preserving leucocyte (particularly neutrophil) morphology for light microscopy.
      CPP performed as well as K3EDTA for other routine haematology measurements and
      was found to be stable at room temperature for at least one year. The increased
      cost of CPP will prevent its widespread use, but compatibility with K3EDTA will
      allow it to be used along with K3EDTA in situations where transit times to the
      laboratory regularly exceed 24 h.

PMID- 8130693
TI  - Lymphocyte phenotypes in infants are altered by separation of blood on density
      gradients.
AB  - Flow cytometry techniques for immunophenotyping have revolutionised the diagnosis
      and monitoring of paediatric immunological disorders. Although recent studies in
      adult subjects discourage the use of density gradients for cell preparation prior
      to phenotyping, these procedures continue to be used. The purpose of this study
      was to determine the effect of density gradient separation on lymphocyte
      phenotypes from neonates, infants, and adults as compared to whole blood
      determinations. Subset distributions were different with the two procedures. In
      all three groups, CD19+ (B cell) and CD8+ (suppressor/cytotoxic T cell)
      percentages were significantly lower and CD3-CD56+ (NK cell) percentages were
      significantly higher in the density gradient separated cells. The loss of CD8+
      cells in density gradient separation was shown to be a selective event. The
      CD8+CD11b- (cytotoxic T) subset percentages were lower in the density gradient
      separated cells, while the percentages of CD8+CD11b+ (suppressor T) cells were
      not affected by separation procedure. Because of the selective loss of
      lymphocytes on density gradients, the use of a whole blood technique for
      immunophenotyping in paediatric subjects is recommended.

PMID- 8130694
TI  - Red cell antibody screening and identification: a comparison of two column
      technology methods.
AB  - Two commercial column techniques for use in antibody screening and identification
      procedures were tested in parallel with 1000 random samples sent for ante-natal
      serological investigation. The DiaMed ID microtyping system uses a sephadex gel
      contained in microtubes, either neutral or impregnated with anti-human globulin
      (AHG), for use in two-stage enzyme methods and LISS indirect antiglobulin testing
      (IAT) respectively. The Ortho Biovue technique consists of a slurry of micro
      glass spheres which act as the filter to retain haemagglutination reactions
      within the matrix. Columns containing AHG also possess a macromolecular density
      barrier to prevent test serum from passing into the column and neutralising the
      AHG. Both systems offer the advantage of 'no-wash' IAT, which minimises the
      potential for problems and errors associated with conventional spin-tube
      techniques. In this comparison of the two column methods, antibody detection
      rates were found to be similar and the sensitivity of both methods was
      comparable, although the Biovue technique was prone to exhibit equivocal results,
      particularly in the IAT.

PMID- 8130695
TI  - Flow-cytometric analysis of lymphocytes, leukaemias and lymphomas.
AB  - Flow cytometry may be used for immunophenotypic and karyotypic analysis of cells.
      The aim of this review is to provide insight into how the different leukaemias
      and lymphomas may be diagnosed by flow cytometry.

PMID- 8130696
TI  - Bladder and prostate cancer screening for human papillomavirus by polymerase
      chain reaction: conflicting results using different annealing temperatures.
AB  - Two sets of L1 ORF degenerative primers, GP5/6 and MYO9/11, have been used to
      screen for human papillomavirus (HPV) sequences in bladder tumours, cell lines
      and controls by polymerase chain reaction (PCR). None of the 14 bladder and
      prostate tumours or nine bladder cell lines contained HPV sequences when tested
      with L1 ORF primer pair GP5/6 at 40 degrees C annealing temperature. In contrast,
      use of the L1 ORF primer pair MY09/11 at this low annealing temperature
      consistently gave a 450 bp band, suggesting the presence of HPV. This occurred in
      all samples including the negative DNA controls. An increase in stringency to an
      annealing temperature of 55 degrees C resulted in an elimination of this band in
      the test and negative control samples. This finding may explain why there are
      contradictory reports in the literature, and further studies are in progress to
      clarify this issue.

PMID- 8130697
TI  - Serum bromide measurements in infants below 1000 g, for determination of
      corrected bromide space.
AB  - We describe modifications to the gold colorimetric method for the measurement of
      serum bromide in the estimation of extracellular fluid volume. These
      modifications allow the application of the bromide dilution technique to small
      infants, below 1000 g birth weight, since sample volumes as small as 50
      microliters may be assayed.

PMID- 8130698
TI  - The need for chaperones. Chaperones are expensive and time consuming.

PMID- 8130699
TI  - The need for chaperones. Chaperones valuable in difficult psychiatric interviews.

PMID- 8130700
TI  - Community-based substance abuse prevention research: rhetoric and reality.

PMID- 8130701
TI  - Reaching hidden populations of drug users by privileged access interviewers:
      methodological and practical issues.
AB  - The methodological issues surrounding the use of a privileged access interviewer
      team to generate a network sample of drug users are examined. Traditionally
      network samples have tended to be used by qualitative researchers. Privileged
      access interviewing provides a mechanism for the application of a structured
      instrument to a network sampling model. In doing so some problematic issues in
      this area for structured methodology are overcome, reduced or standardized. The
      use of this method is appraised in terms of meeting the methodological
      requirements of the Drug Transitions study. The practical experiences of our
      group in using a privileged access interviewer team to interview more than 400
      heroin users, many of whom were not in contact with treatment services, are
      discussed. This method is most appropriate for the quick collection of data, from
      diverse networks of drug users, by use of a structured instrument. Success is
      likely to be dependent on careful implementation. The ongoing monitoring of data
      quality is of particular importance, as is good management practice and the
      establishment of supportive and non exploitative relationships with the
      interviewer team.

PMID- 8130702
TI  - Evidence of normal emotional responsiveness in alcoholic Korsakoff's syndrome in
      the presence of profound memory impairment.
AB  - Memory and likeability ratings for emotion-laden and neutral stimuli were
      investigated in Korsakoff amnesics, former heavy drinkers and light drinkers.
      Tasks were recall of self-generated paired-associates, primed recognition and
      likeability ratings for faces previously paired with emotional or neutral
      descriptors, and ratings of the emotionality of items in a 64-word list. The
      Profile of Mood States and Geriatric Depression Scale were also administered.
      Despite severely impaired recall in Korsakoff's amnesics, the effects of
      emotional versus neutral material were not distinguishable among the three
      groups. These findings indicate a need to re-examine the notion that flattening
      of emotional responsiveness is a central characteristics of Korsakoff's Syndrome.

PMID- 8130703
TI  - Time to alcohol dependence after abstinence and first drink.
AB  - The first relapse into alcohol dependence after abstinence is characterized by
      sudden immoderate drinking. The time after abstinence to re-establishing
      dependence has never been compared to the time taken to establish dependence
      initially. Thirty one subjects who had been dependent on alcohol, had
      subsequently been abstinent for at least 2 months, and had had a relapse into
      dependence were interviewed. The median time to first dependence on alcohol was
      13 years (Mean (SD) 14.7 (8) years); median time to dependence when relapsing was
      7 days, a 700-fold acceleration (p < 0.00003). Only three subjects drank for more
      than 30 days (range 90-1825 days) before re-establishing dependence; the average
      was 82 (330) days overall and 9.3 (8.0) days if these subjects were excluded.
      Times to initial and subsequent dependence were not correlated nor related to the
      duration of abstinence (median 9, mean 16.9 (22) months). While abstinent the
      subjects had felt as if they were healed. It should be emphasized to abstinent
      patients that alcohol dependence has a latent sequel: they are at risk of
      accelerated dependence after recurrent drinking, which should be regarded as an
      emergency.

PMID- 8130704
TI  - The influence of perceived social support on the relationship between family
      history of alcoholism and drinking behaviors.
AB  - The present study examined the effect that perceived social support has on the
      relationship between having a family history of alcoholism and alcohol use in a
      sample of 85 adult children of alcoholics and a control group (n = 68). Social
      support from both peers and from family members were assessed for their potential
      differential effects. Gender differences were also examined. Overall, perceived
      social support from friends significantly moderated the relationship between
      family history of alcoholism and several indicators of alcohol use. In contrast,
      perceived social support from family members did not moderate any of the
      relationships examined. These findings emphasize the importance of considering
      different sources of social support when using social support as a moderating
      variable and the need to examine the underlying processes and variables involved
      in the relationship between having a family history of alcoholism and alcohol
      use.

PMID- 8130705
TI  - Suicide, alcohol, and divorce; aspects of gender and family integration.
AB  - Both over time and between countries within our cultural domain there seems to be
      a persistent male predominance in the suicide rate. Based on Durkheim's theory of
      social integration as a key issue in egoistic suicide, the present study aimed at
      analyzing two empirically operational aspects of social disintegrative factors on
      the male and female suicide rates in Norway; namely alcohol consumption and
      divorce. Times series analyses on differenced data from 1911 to 1990 showed that
      both alcohol consumption and divorce were independently and statistically
      significantly associated with the male suicide rate, but not with the female
      suicide rate. The results are discussed on basis of gender roles and social
      integration.

PMID- 8130706
TI  - Predictive validity of the Readiness to Change Questionnaire.
AB  - Following the development of the Readiness to Change Questionnaire described by
      Rollnick et al., this article reports on the predictive validity of the
      questionnaire among a sample of 174 male excessive drinkers identified by
      screening on wards of general hospitals. Relationships between patients' "stage
      of change" derived from questionnaires administered prior to discharge from
      hospital and changes in drinking behaviour at 8 weeks and 6 months follow-up are
      analysed. Allocated stage of change provided statistically significant
      relationships with drinking outcome. Multiple regression analysis showed that
      stage of change remained a significant predictor of changes in alcohol
      consumption when other possible predictors were taken into account. Two methods
      for allocating stage of change on the basis of questionnaire responses for use in
      different circumstances, a "quick" and a "refined" method, are described.

PMID- 8130707
TI  - Opiate users and the first years after treatment: outcome analysis of the
      proportion of follow up time spent in abstinence.
AB  - This second report on a follow-up study of drug users focuses on changes that
      occurred on a number of variables between intake and follow-up and during the
      follow-up period. The length of abstinence from opiates was considered as a
      proportion of the total follow-up period. Overall there was a reduction in opiate
      use, in injecting and sharing equipment at follow-up. There had been, however, a
      high level of these risky activities during the follow-up period. Sustained
      abstinence from opiates was associated with increased employment, enhanced social
      stability and mental health. Intake drug use was strongly related to follow-up
      drug status. In particular, those who were injectors of multiple drugs at intake
      were far less likely to be long term opiate abstainers at follow-up than those
      who were not injectors at intake or injectors of opiates only.

PMID- 8130708
TI  - An interview study of participants in the Tacoma, Washington, syringe exchange.
AB  - Although European and Australian studies of syringe exchange programs have
      reported safer injection among participants and no increase in drug use, the
      generalizability of these findings to the US is uncertain. We report on the
      operations and potential effectiveness of the longest-operating syringe exchange
      in the US and compare our results to studies of exchange programs outside the US.
      The sample of 204 study subjects reported no change in the frequency of
      injection, from 155 to 152 injections per month, and a decline in the frequency
      of unsafe injections, from 56 to 30 times per month, while participating in the
      program. In all studies, participants report reduction in unsafe injections, and
      no increase in illicit drug use. However, the comparison also suggests that a
      high proportion of Tacoma exchangers have higher initial rates of drug injection,
      unsafe injection and homelessness, all of which were associated with unsafe
      injection while using the exchange. These indicate a need for additional services
      but that the Tacoma program is no less effective than European and Australian
      programs.

PMID- 8130709
TI  - Predictors of successful smoking cessation following advice from nurses in
      general practice.
AB  - At follow-up of 751 subjects receiving a brief nurse-administered anti-smoking
      intervention in general practice, 135 subjects (18%) reported stopping smoking,
      of whom 44 (6%) reported sustained cessation for one year. The demographic,
      social and attitudinal characteristics of these subjects were compared with 616
      subjects who continued to smoke. The most important predictors of cessation were
      intention to stop (OR 5.1, 95% CI 2.1-12.0), personal rating of likelihood of
      cessation (OR 4.9, 95% CI 2.8-8.5), nurse rating of likelihood of cessation (OR
      4.0, 95% CI 2.2-7.4), and smoking habit of partner (1.9, 95% CI 1.3-2.9). As
      practice nurses are able to distinguish likely quitters from those who are not
      motivated and less likely to succeed, it is important to decide whether it is
      more cost effective to target support at the motivated or to spend more time
      encouraging less motivated. The most challenging, but possibly the most
      rewarding, task is to try to reduce the high proportion of new ex-smokers who
      relapse. Although 41.1% (95% CI 28.1, 58.0) of those expressing a definite
      intention to stop smoking gave up, only 17.9% (95% CI 8.9, 30.4) achieved
      sustained cessation. However, as sustained cessation is strongly predicted by
      social variables, such as marital status and time spent in the company of
      smokers, preventing relapse may not be easy to achieve through medical
      intervention alone.

PMID- 8130710
TI  - Guidelines for the prevention and treatment of benzodiazepine dependence: summary
      of a report from the Mental Health Foundation.

PMID- 8130711
TI  - Comparison of DSM-III-R and draft DSM-IV alcohol abuse and dependence in a
      general population sample.
AB  - The purpose of this Data Note was to compare DSM-III-R and Draft DSM-IV
      formulations of alcohol use disorders in terms of prevalence and overlap in a
      representative sample of the United States general population. The prevalence of
      DSM-III-R and DSM-IV alcohol abuse and dependence combined were strikingly
      similar, despite discrepancies in the separate component diagnoses of abuse and
      dependence. The major finding of this study showed a reversal of the abuse-to
      dependence ratio associated with the DSM-IV classification. Unlike previous
      surveys using DSM-III-R definitions, the prevalence of DSM-IV abuse exceeded that
      of dependence in this general population sample. Reasons for this discrepancy
      were discussed in terms of the differences in the number and content of abuse and
      dependence criteria and the relationship between abuse and dependence categories.
      The need for an explicit statement justifying the changes in the DSM-IV
      classification is highlighted.

PMID- 8130712
TI  - Childhood cancer around nuclear installations.
AB  - There is an increased incidence of childhood cancer, particularly lymphocytic
      neoplasia, in children who live close to nuclear installations. Possible causes
      are radiation-induced germ line mutations in occupationally exposed parents, or
      radiation-induced somatic mutation in the developing cells of the fetus or child
      due to increased environmental exposure. An alternative possibility is that the
      socioeconomic characteristics of the communities lead to an altered response to
      infection in childhood and this increases the risk of lymphocytic neoplasia in
      particular. For sites other than Sellafield in the UK, the evidence linking
      childhood cancer to radiation is unconvincing and it is possible that the
      increase is entirely due to the social characteristics of the communities. In
      Seascale, a village close to Sellafield, however, the increase is more marked and
      it is unlikely that social factors alone can explain the change. Furthermore, the
      environmental discharges from Sellafield are much higher than from other sites,
      and approach levels which could have a measurable effect on cancer incidence. In
      spite of a great deal of epidemiological investigation, no clear answer is
      available. It is argued that in order to solve the problem we must use new
      knowledge from molecular genetics and measure the rate of somatic mutation in
      those who work in the nuclear industry and in those who live nearby.

PMID- 8130713
TI  - The effect of different sampling devices on the presence of endocervical cells in
      cervical smears. A systematic literature review.
AB  - A literature search examined 39 reports on the relationship between the absence
      of endocervical cells in a cervical smear and the sampling technique used. Using
      (pooled) ratios we compared the results for different pairs of sampling devices,
      thereby controlling for the design of each study when appropriate. The Cytobrush
      appears the most efficient sampling method with regard to the presence of
      endocervical cells. Combining the results of this review with the results of a
      previous meta-analysis on the effect of the sampling technique on the detection
      of pathology, the combined spatula and Cytobrush technique seems to be the best
      sampling method.

PMID- 8130714
TI  - Progress in the fight against cancer in EC countries: changes in mortality rates,
      1970-90.
AB  - The question of how much effective progress against cancer is being made has been
      raised repeatedly during the last decade; one approach to evaluating such
      progress is represented by the analysis of mortality, which has been used by
      several researchers. Here we report mortality trends for 1970-90 for four age
      groups, calculated for each 3-year period, and presented as the percentage change
      of the rate of the first period examined. Detailed graphs for each country and
      for the European Community as a whole are presented for 'all cancers', and for
      cancer of the colon-rectum, lung, breast and ovary. For other cancers (stomach,
      melanoma, uterus, testis and Hodgkin's disease), the graphs are presented only
      for the whole of the European Community. Variations in mortality are discussed,
      in terms of changes in incidence, efficacy and diffusion of prevention, as well
      as improvement in diagnosis and treatment.

PMID- 8130715
TI  - Levels of cadmium, zinc and copper in renal cell carcinoma and normal kidney.
AB  - Levels (microgram/g dry weight) of cadmium (Cd), zinc (Zn) and copper (Cu) were
      determined in kidneys with renal cell carcinoma from 20 male and 11 female
      patients. Autopsied kidneys from nine males and eight females who had died of
      nonmalignant diseases were used as controls. The mean levels in cortex of Cd was
      in cases 103.2 and in controls 79.9 (not significantly different). For non
      smoking cases, mean level of Cd in cortex was somewhat lower than in the
      controls. No significant differences were found between cases and controls for Cd
      levels in the medulla. Zn in cortex was significantly lower in the cases aged >
      or = 69 years (mean 182.0) than in the corresponding controls (mean 237.6). Zn in
      medulla was significantly lower in all cases (mean 103.5) than in controls (mean
      162.2). The mean level of Cu in the medulla in cases was 10.7 and in controls
      13.0 (P = 0.05). No differences were found for Cu levels in cortex.

PMID- 8130716
TI  - Soil fertility factors in relation to oesophageal cancer risk areas in Transkei,
      southern Africa.
AB  - Soil samples were collected during certain years for the period 1982-89 from high
      and low-risk areas for oesophageal cancer in Transkei, southern Africa. These
      samples were taken either from cultivated soils under maize monoculture, or from
      uncultivated soils (1989 only) adjacent to the maize fields. Analyses of mineral
      elements in the soil samples were performed at two independent laboratories.
      Furthermore, soil and maize leaf samples, from field trials in a high- and a low
      risk area for oesophageal cancer were analysed. The results from this study do
      not agree with those reported previously for Transkei. Cultivated soils in both
      high- and low-risk areas were found to be highly fertile. The levels of Mn, Ni,
      Mg, Ca, K and soil pH were significantly higher, and Al, Fe and organic matter
      significantly lower in the high-risk compared with the low-risk area. Leaf
      analysis, although not tested statistically, indicated higher levels of Mn K, Ca
      and Fe, and lower levels of P, in the high-risk area.

PMID- 8130717
TI  - Persistent viral infections in human carcinogenesis.
AB  - Several taxonomically distinct human pathogenic viruses capable of upholding
      persistent infections have been recognized as important carcinogens. Jointly they
      are characterized by going into decade-long interactions with host cells and/or
      tissues. Tumours arise after a long latent period in a few infected individuals.
      The cellular changes necessary for malignancy are only in part directly or
      indirectly caused by virus-cell interactions. Cofactors are assumed to be
      involved. The different routes to malignancy reflect the distinct strategies of
      each virus in its interaction with the host, which for the upkeep of chronic
      infections requires a tight control of both virus and cell multiplication and the
      extent to which an immune response is provoked. The size of the virus-cancer
      problem and the possibility of prevention makes virology one of the most
      promising areas of cancer prevention on a global scale. A much wider use of the
      vaccination against hepatitis B, especially in children, is warranted in
      developed countries.

PMID- 8130718
TI  - DNA content of rectal mucosa and rectal mucosal proliferation in individuals at
      high risk of colorectal cancer.
AB  - Genetic changes are important in the development of colorectal cancer. Ploidy and
      rectal mucosal proliferation were measured in histologically normal rectal mucosa
      of 85 individuals (mean age 59 years, range 29-74) who had a total colonoscopy.
      Fifty-one subjects had an adenoma or were undergoing adenoma surveillance. Twenty
      two subjects had a strong family history of colorectal cancer and 12 individuals
      comprised a control group who had a normal colonoscopy without a family history
      of colorectal cancer. An abnormal DNA content (aneuploidy) was found in the
      normal mucosa of nine (10.6%) individuals. There was no significant difference in
      rectal mucosal proliferation with those who had aneuploidy and those who had
      diploidy. There was a trend towards increased proliferation in those with
      aneuploidy and adenomas, compared with controls. Of the 35 individuals undergoing
      adenoma surveillance, eight had recurrent adenomas, and three of these expressed
      aneuploidy. In the other 27, in whom no adenomas were found, no individual
      expressed aneuploidy (P = 0.01, Fisher's exact test). Aneuploidy within
      histologically normal mucosa is an unusual feature, which requires further
      investigation, particularly in patients developing adenomas.

PMID- 8130719
TI  - Results, toxicity and compliance in chemoprevention trials of head and neck
      cancer.
AB  - Several clinical trials have demonstrated the efficacy as chemopreventive agents
      on upper aerodigestive tract (UADT) cancer of vitamin A or its natural precursor,
      beta-carotene, or its synthetic analogues, retinoids. Particularly, 13-cis
      retinoic acid (cRA) has been shown to reverse oral leukoplakia and to reduce the
      frequency of second primary tumours in patients treated for head and neck cancer.
      Since chemopreventive treatments must be of very long-term duration (even years),
      and because of apparent 'good health' of treated patients, the toxicity of used
      drugs and the compliance with treatment need to be carefully considered. Current
      clinical research has evaluated the efficacy of low doses of cRA in larger
      numbers of patients, and the increased effectiveness of cRA when used in
      combination with recombinant alpha-interferon 2a (r-alpha-IFN 2a) has also
      produced high objective response rate in patients affected with squamous cell
      carcinoma of the head and neck. In vitro and in vivo studies to verify the
      validity of several biomarkers (in particular micronuclei) as intermediate end
      points in chemoprevention studies are continuing, to allow the short-term
      screening of promising chemopreventive drugs to be used in clinical trials. The
      published literature on this matter is reviewed, with special attention to
      retinoid treatment and toxicity/compliance-related problems, and compared with
      our own experience.

PMID- 8130720
TI  - Environmental genotoxicity and cancer risk in humans: a combined evaluation
      correlating the results of the Tradescantia micronucleus assay in the field and
      human biomarker assessments in serum. I. The TRAD-MCN assay.
AB  - It is well documented that environmental pollution from industrial activity,
      sewage farms, hazardous waste sites, incinerators, etc, contributes to the
      overall cancer risk and that this contribution can be considerable under certain
      circumstances. It is important, therefore, to identify the level of genotoxic
      activity in the environment and to relate it to biomarkers of cancer risk in
      humans. After reviewing a range of cytogenetic assays, we have selected the
      Tradescantia micronucleus assay (TRAD-MCN) developed by Ma et al to be used in
      indoor and field evaluations. The meiotic pollen mother cells of T clone 4430 are
      particularly sensitive to chemical pollutants; the buds are exposed for 6-8 h. We
      describe assays made down wind from a coal-fired power station and from the
      vicinity of two waste sites. Statistically significant results were obtained at
      200 m and 600 m down wind from the power station; higher levels of micronucleus
      frequencies (MN) were found in foggy rather than dry conditions. Similarly, in
      the vicinity of two waste sites the MN frequencies were significantly increased
      in both dry and foggy conditions up to 1.5 km down wind; this was despite
      previous efforts to rehabilitate the sites. The TRAD-MCN assay is sensitive,
      reproducible, easy to perform, well standardized, inexpensive and undemanding in
      equipment. We propose that it be the primary test for genotoxicity evaluation and
      mapping followed, in suspicious areas, by human biomarker assays.

PMID- 8130721
TI  - Europe against Cancer breast cancer screening programme in France: the ADEMAS
      programme in Bas-Rhin.

PMID- 8130722
TI  - Screening for breast cancer in Ireland: the Eccles Breast Screening Programme.
AB  - The Eccles Breast Screening Programme is a population-based screening programme
      for breast cancer, based at the Mater Misericordiae Hospital, Dublin. It began in
      1989 simultaneously with similar programmes in Belgium, France, Greece, Portugal
      and Spain. The objectives of the Eccles Programme are: (i) to evaluate the impact
      of mammographic screening on morbidity and mortality from breast cancer in Irish
      women; and (ii) to address the feasibility and potential value of a national
      breast cancer screening programme. The specific group targeted for screening is
      women born in 1925 to 1940 inclusive, in a defined geographical area comprising
      north Dublin City and County, and Counties Cavan and Monaghan. The areas combined
      comprise 16% of the country's population; just over 29,000 women were invited for
      screening. An analysis of the demographic and socioeconomic features of the
      target population reveals that it represents the total population remarkably
      well. Participants were invited from a population register to attend one of two
      screening units. Follow-up treatment for those with abnormalities takes place
      predominantly at the Mater Hospital where the facilities of the Departments of
      Pathology, Surgery and Oncology have been made available to the programme. Almost
      18,000 women had a mammogram in the first round of screening, an overall response
      rate of 62%. A total of 129 cancers were detected, a prevalence of breast cancer
      of 7.2 per 1,000. Of those, 15 (11.6%) were entirely intraduct, and an additional
      7 (5.4%) had minimal invasion. This is considerably higher than the proportion of
      intraduct cancers seen in referral practice populations.

PMID- 8130723
TI  - Design and preliminary results of the Florence Breast Cancer Screening Programme
      (Progetto Firenze Donna).

PMID- 8130724
TI  - Breast cancer screening in the framework of the Europe against Cancer programme.

PMID- 8130725
TI  - Breast cancer screening in southern Greece.

PMID- 8130726
TI  - Early detection programme for breast cancer in Navarra, Spain.

PMID- 8130727
TI  - Breast cancer screening in the central region of Portugal.

PMID- 8130728
TI  - Breast cancer screening in the Flemish region, Belgium.

PMID- 8130729
TI  - The plasminogen activator and inhibitor system in bone remodelling.
AB  - The neutral protease, plasmin, is generated by plasminogen activators, and is
      ascribed an important role in several physiological and pathological
      circumstances characterized by tissue remodelling and cell motility. The two
      types of plasminogen activator, tissue-type (tPA) and urokinase-type (uPA), are
      produced by osteoblasts, as is the specific PA inhibitor, PAI-1. Some hormones
      which activate bone resorption increase PA activity produced by osteoblasts, by
      decreasing the production of PAI-1. The increased PA activity has been suggested
      to facilitate bone resorption by activating latent collagenase, thus preparing
      the bone surface for osteoclastic resorption. Targeted and regulated production
      of plasmin might also contribute to the coupling of bone formation to resorption,
      by activating latent TGF beta in bone, and activating IGF-1 by freeing it from
      association with inhibitory binding protein. TGF beta itself is a powerful
      inhibitor of PA activity, an effect achieved by enhancing mRNA and protein for
      PAI-1. Thus the PA system is a potentially important regulatory system in bone
      remodelling, whose local activity is controlled through concerted actions of
      hormones and locally generated growth factors and cytokines.

PMID- 8130730
TI  - Calcitonin gene related peptide stimulates differentiation of neonatal rat
      myogenic cultures.
AB  - The effect of the nerve derived peptide, calcitonin gene related peptide (CGRP)
      on myoblast fusion/differentiation was studied in rat myogenic cell cultures,
      using creatine kinase activity as an index of fusion. Addition of CGRP at 10(-7)
      M to myoblast cultures resulted in an enhancement of kinase activity after 11
      days of treatment. This response was not accompanied by increased protein content
      of cultures implying an effect primarily on fusion rather than on myotube
      growth/size. Neither was it a direct effect on enzyme activity alone since no
      increase in creatine kinase activity occurred when CGRP was added to mature
      myotube cultures. These data suggest a role for CGRP in the myoblast fusion
      process itself and raise questions as to its importance in the growth and
      development of muscle in vivo.

PMID- 8130731
TI  - Effects of chronic lithium treatments on central dopaminergic receptor systems: G
      proteins as possible targets.
AB  - Numerous biochemical and electrophysiological studies have proposed a role for
      dopamine (DA) in the therapeutic efficacy of lithium (Li+) salts. The effects of
      ex vivo chronic Li+ treatments on neostriatal DA receptors, as well as on the G
      protein adenylyl cyclase complex and on tissue cAMP levels were investigated in
      adult rats. The animals were administered LiCl in their drinking water (1 g/l)
      for varying periods of time, i.e. 1, 15 and 28 days. After sacrifice by
      decapitation, their brains were removed and the neostriatum dissected out to
      assay DA receptors and adenylyl cyclase activity. The antagonists [3H]SCH23390
      and [3H]raclopride were employed to label D1 and D2 receptors, respectively.
      Chronic Li+ treatments did not modify the saturation binding of either ligand.
      However, competition studies of the same antagonists by DA revealed biphasic
      curves, and the inhibition constant of the high-affinity site was significatively
      increased after chronic Li+. The data suggest an alteration in the coupling
      efficacy between G proteins and DA receptors. Moreover, chronic (28 day) Li+
      treatment, but not a 1 day Li+ administration, lead to a reduction of the GTP
      induced and DA-sensitive adenylyl cyclase activity, without changes in the basal
      activity or in forskolin-induced cAMP production. The results demonstrate that
      chronic Li+ treatments diminish neostriatal dopaminergic activity, probably
      through a direct action on the G protein itself. The underlying mechanisms do not
      appear to involve modifications in either the D1 or the D2 receptor primary
      ligand recognition sites, but may represent alterations in both the coupling
      process and the capacity of the G proteins, once activated, to stimulate adenylyl
      cyclase.

PMID- 8130732
TI  - Chronic desipramine treatment influences D1 stimulation and D2 inhibition (dual
      control) of adenylate cyclase by dopamine in rat striatum.
AB  - The response of adenylate cyclase to GTP and to dopamine (DA) was investigated in
      striatal membranes from desipramine (DMI)- or saline-treated rats. DMI (15 mg/kg)
      or saline was injected i.p. once a day for 3 weeks. In saline-treated control
      membranes, GTP exerted a biphasic effect on basal and DA-stimulated enzyme
      activity; peak levels of stimulation by DA plus GTP were observed at 1 microM
      GTP. On the other hand, peak levels moved to the right in the GTP dose response
      curve in DMI-treated membranes. Therefore, D2 inhibition might be attenuated,
      while the D2 specific agonist, PPHT, was not observed to cause inhibition of
      adenylate cyclase. Furthermore, D1 stimulation of adenylate cyclase via D1
      specific agonist SKF was attenuated in DMI-treated membranes. It seems,
      therefore, that chronic treatment of rat striatum with DMI exerts a dual
      influence, that is, a lessening of both D1 stimulation and D2 inhibition of
      adenylate cyclase, and alters specifically the overall process of the adenylate
      cyclase system.

PMID- 8130733
TI  - Increased susceptibility to oxidation of vitamin E in mitochondrial fractions
      compared with synaptosomal fractions from rat brains.
AB  - The in vitro oxidation of vitamin E (alpha tocopherol) in rat brain synaptosomes
      and mitochondria by 2,2'-azo-bis-(2'-amidinopropane) dihydrochloride (ABAPH), a
      free radical generator, was studied. Subcellular fractions (300 micrograms total
      protein) were suspended in different buffers at pH 7.4 and incubated at 37
      degrees C. In the presence of 0.5 mM ABAPH the mitochondrial alpha tocopherol
      began to get oxidized after a lag time or induction time of 15 min compared with
      a lag time of 30 min for the synaptosomal fraction. Thus the reserve of reducing
      compounds that are responsible for delaying tocopherol oxidation is less in
      mitochondria than in synaptosomes. More tocopherolquinone was produced during
      incubations without ABAPH compared with incubations in the presence of ABAPH
      suggesting that the mechanism of oxidation of tocopherol differs under these two
      conditions. When mitochondria were incubated in buffer without oxidants the
      production of tocopherolquinone preceded that of thiobarbituric acid reactive
      substances, an indicator of peroxidation of fatty acids. Therefore, alpha
      tocopherol is active as an anti-oxidant in mitochondrial membranes and the
      production of alpha tocopherolquinone could be a monitor of mild membrane
      oxidation under in vitro conditions. The ease of oxidation of mitochondrial
      tocopherol suggests a general vulnerability of the mitochondrial membranes to
      oxidation. Adding vitamin E or its water soluble analogs during in vitro
      experiments may improve the stability and viability of mitochondria. Furthermore,
      antioxidant protection by vitamin E may be crucial for the maintenance of
      tissues, such as brain, whose function is critically dependent upon the
      availability of high energy phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130734
TI  - Involvement of protein kinase C activation in regulation of acetylcholine release
      from rat hippocampal slices by minaprine.
AB  - Involvement of protein kinase C (PKC) activation in the regulation of
      acetylcholine (ACh) release from rat hippocampal slices by minaprine, [3(2
      morpholinoethylamino)-4-methyl-6-phenylpyridazine] was investigated. Phorbol
      esters such as 4 beta-phorbol 12,13-dibutylate (PDBu) and 12-o
      tetradecanoylphorbol 13-acetate (TPA) enhanced high K(+)-evoked [3H]ACh release
      from rat hippocampal slices. The enhancing effect of phorbol ester was attenuated
      by PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2
      methylpiperazine (H-7). However, the inactive phorbol analogue, 4 alpha-phorbol
      12,13-didecanoate (PDD) had no effect on [3H]ACh release. Minaprine and 4
      aminopyridine (4-AP) attenuated the inhibitory effect of 5-hydroxytryptamine (5
      HT) on high K(+)-evoked [3H]ACh release from rat hippocampal slices. The
      attenuating effect of minaprine on the inhibition of [3H]ACh release by 5-HT was
      prevented by staurosporine, while that of 4-AP was not influenced. Furthermore,
      PDBu blocked voltage-dependent, rapidly inactivating 42K efflux from rat brain
      synaptosomes. These results suggest that minaprine attenuates the inhibitory
      effect of 5-HT on ACh release via PKC activation in rat hippocampus, and that the
      blockade of the K+ channel with PKC activation might be involved in the action of
      minaprine.

PMID- 8130735
TI  - Mannose dependent tightening of the rat ependymal cell barrier. In vivo and in
      vitro study using neoglycoproteins.
AB  - The possible role of carbohydrate binding proteins (lectins) and glycoconjugates
      in the formation of junctions ensuring tightening between ependymal cells was
      studied using synthetic glycoconjugates, the neoglycoproteins. These compounds
      are prepared by substituting bovine serum albumin with sugar residues and
      additional labelling (or not) with fluorescein or biotin. Injections of these
      components into the cerebral ventricles of adult rats resulted in a binding
      pattern which could be related to their carbohydrate composition. Mannose
      containing neoglycoproteins were bound to ependymal cell cilia and penetrated
      rapidly the brain tissue. Such phenomenon was not seen with glucose- or galactose
      containing neoglycoprotein molecules. In contrast, mannose-, galactose- and
      glucose-containing neoglycoproteins bound strongly to some endothelial cells
      around blood vessels. Fluorescent unglycosylated serum albumin did not bind to
      any brain structures. In contrast, co-injection of mannose-containing non
      fluorescent neoglycoproteins with the other fluorescent compounds (including
      fluorescent sugar-free BSA) resulted in the penetration of the fluorescent
      compounds into the brain tissue. This internalization into brain was attributed
      to disaggregation of junctions between ependymal cells. Cultured ependymal cells
      behaved likewise. In short term experiments (5 min-1 h), only the mannose
      containing neoglycoproteins bound strongly to the ependymal cells, particularly
      to the cilia. In long term experiments (1-9 days), mannose-containing
      neoglycoproteins specifically induced the disappearance of junctions between the
      cultured cells. These results emphasize the importance of mannose-dependent
      recognition system in the maintenance of junctions between ependymal cells, where
      a mannose-binding lectin has been previously detected.

PMID- 8130736
TI  - Intracerebroventricular administration of nerve growth factor affects muscarinic
      cholinergic receptors in the cerebral cortex of neonatal rats.
AB  - The repeated intracerebroventricular administration of nerve growth factor (5
      micrograms/2.5 microliters) to neonatal rats induced the activation of choline
      acetyltransferase in forebrain cholinergic neurons that was paralleled by a
      concomitant change in the density of muscarinic cholinergic receptors in the
      cerebral cortex. The administration of nerve growth factor altered muscarinic
      binding sites in a biphasic fashion during postnatal development. A significant
      stimulation of the developmental increase in the density of muscarinic binding
      sites occurred in nerve growth factor-treated animals at days 2 and 3 after
      birth. Conversely, nerve growth factor induced a significant decrease in the
      receptor number at postnatal days 8 and 14. Muscarinic receptor number returned
      to control values after treatment, suggesting that nerve growth factor-induced
      changes to muscarinic cholinergic receptors are reversible. Nerve growth factor
      administration did not affect muscarinic cholinergic receptor density in striatal
      membranes and did not alter the relative content of cortical messenger RNAs
      encoding m1 and m3 muscarinic cholinergic receptor subtypes at postnatal day 14,
      as determined by reverse transcriptase-polymerase chain reaction. The up- and
      down-regulation of muscarinic cholinergic receptors induced by nerve growth
      factor during postnatal development may be temporally related events associated
      with concomitant changes in the activity of choline acetyltransferase.

PMID- 8130737
TI  - Sodium valproate induced alterations in monoamine levels in different regions of
      the rat brain.
AB  - Sodium valproate is a well established anticonvulsant drug but its exact mode of
      action is not yet clear. With a view to find out whether the mechanism of action
      of sodium valproate is mediated by alteration in monoamine levels, apart from
      GABA, in brain, sodium valproate (200 mg/kg body wt) was administered i.p. to
      male adult Wistar rats for 45 days. The levels of norepinephrine (NE), dopamine
      (DA) and serotonin (5-HT) were assayed in different brain regions using high
      performance liquid chromatographic (HPLC) method. It was noted that at the end of
      the experimental period there was no change in body or brain weight nor were
      there any neurological deficits as a result of sodium valproate administration.
      However, after administration of sodium valproate there was a significant
      increase in norepinephrine levels in hippocampus (P < 0.01) and brainstem (P <
      0.01) while a significant decrease was noted in hypothalamus (P < 0.001).
      Dopamine levels were significantly increased in motor cortex (P < 0.01),
      hippocampus (P < 0.01) and hypothalamus (P < 0.001). Serotonin levels were
      significantly increased in striatum-accumbens and brain stem (P < 0.001). However
      a marginal increase was also observed in motor cortex and hippocampus. 5-HT
      levels were significantly decreased in hypothalamus (P < 0.001) and cerebellum (P
      < 0.01). The present findings suggest the possibility that the anticonvulsant
      effect of sodium valproate could be due to alterations in monoamine levels apart
      from its action on GABA, which would indicate also the efficacy of this drug in
      different types of seizures.

PMID- 8130738
TI  - Characterization of [3H]inositol 1,4,5-trisphosphate binding sites in human
      temporal cortical and cerebellar membranes.
AB  - The characteristics of [3H]Ins(1,4,5)P3 binding to human temporal cortical and
      cerebellar membranes have been determined and compared with the binding to calf
      cerebellar membranes. Association and dissociation of ligand was very rapid, k1
      and k-1 values of the order of 7 x 10(7) M-1 min-1 and 0.2 min-1, respectively.
      KD values were 2.7 and 3.5 nM for temporal cortex and cerebellum, respectively.
      The corresponding Bmax values were 165 and 482 fmol/mg protein. Binding was
      influenced in a biphasic manner by calcium. The temporal cortical binding was
      inhibited by Ins(1,4,5)P3 and analogues with the following IC50 values (nM):
      Ins(1,4,5)P3 9.5 and 6.2 (two different salts from different sources),
      Ins(2,4,5)P3 42, Ins(1,3,4,5)P4 670, Ins(1,2,5,6)P4 2620, Ins(3,4,5,6)P4 4300,
      Ins(1,3,4,5,6)P5 5490, InsP(6)5280, Ins(4,5)P2 2600, Ins(1)P 3300, with the IC50
      values for Ins(1,5,6)P3, Ins(1,4)P2 and Ins(4)P being > 25 microM. The IC50 value
      for heparin was 2.1 micrograms/ml. A similar pattern was seen in the cerebellum.
      In both tissues, the Hill slopes were near unity for all compounds except
      Ins(3,4,5,6)P4, where the slope was 0.4. The calf cerebellum had a similar ligand
      specificity (although the potency was generally lower) when values were expressed
      relative to that of Ins(1,4,5)P3, with the possible exception of Ins(1,3,4,5)P4,
      which had a greater relative potency. These data would suggest that in the human
      temporal cortex and cerebellum, [3H]Ins(1,4,5)P3 binding sites are expressed in
      different densities, but have similar properties. There may, however, be species
      differences in the [3H]Ins(1,4,5)P3 recognition site.

PMID- 8130739
TI  - Hippocampal damage produced in rats by alpha-dendrotoxin--a selective K+ channel
      blocker--involves non-NMDA receptor activation.
AB  - The epileptogenic and neurodegenerative effects induced by intra-hippocampal
      injection of a selective K+ channel inhibitor, alpha-dendrotoxin (DTx), were
      investigated in normal rats and those bearing a monolateral surgical lesion of
      the Schaffer collaterals that causes degeneration of their nerve terminals and
      also, isolates the CA3 area. In addition, these effects have also been studied in
      rats pretreated with NBQX, an AMPA receptor antagonist. Injection of DTx (35
      pmol) into one dorsal hippocampus induced motor and electrocortical (ECoG)
      seizures in all the treated animals that were rapid in onset (within 2-3 min).
      The seizures were accompanied at 24 h by significant neuronal cell loss which
      occurred in the CA1, CA3 and CA4 pyramidal cell layers of the hippocampus,
      ipsilateral to the side of injection. This neuronal loss was paralleled by a
      significant decrease in the density of radioiodinated DTx labelled acceptors.
      Lesioning of the excitatory afferents to the CA1 pyramidal cells, gave a
      substantial reduction in the density of radioiodinated DTx labelled acceptors in
      the strata oriens and radiatum, revealing that a proportion of these K+ channels
      are present on the Schaffer collateral terminals. Under these conditions, motor
      and ECoG seizures persisted. As expected, the lesion prevented loss of the
      isolated CA3 pyramids, normally produced by the administration of DTx, leaving
      unaffected CA1 and CA4 pyramidal cell damage, consistent with an observed
      diminution of DTx binding sites in the latter areas. In unlesioned rats pre
      treated with NBQX (30 mg/kg i.p.), subsequent injection of DTx evoked
      epileptogenic effects after a latency of 15 min and caused significant cell loss
      in the CA1 but not in the CA3 and CA4 pyramidal cell layers, ipsilateral to the
      side of toxin injection. A lower dose of NBQX (15 mg/kg i.p.) proved ineffective.
      In conclusion, these data together with our published results on NMDA antagonists
      indicate that motor and ECoG seizures and CA1 pyramidal cell loss elicited by
      intra-hippocampal injection of the K+ channel blocker, DTx, are independent from
      mechanisms involving glutamate-mediated excitotoxicity whereas CA3 and CA4
      pyramidal cell loss may be the consequence of excessive activation of AMPA
      receptors.

PMID- 8130740
TI  - Na+,K(+)-ATPase activity in CNS and noradrenergic neurotransmission: time course
      of differential desipramine (DMI) effects.
AB  - ATPase activities in CNS membranes were studied after administration of
      desipramine (DMI), a noradrenaline (NA) uptake inhibitor. In a previous paper we
      reported that Na+,K(+)-ATPase activity significantly increased 3 h after DMI
      administration (10 mg/kg) in hypothalamus and mesencephalus but not in cerebral
      cortex and pons-medulla oblongata membranes (Viola et al., Cell. molec.
      Neurobiol. 1989, 9, 263-271). Here it was observed that Na+,K(+)-ATPase increase
      induced by acute DMI disappeared at 24 h in hypothalamus but remained during 21
      days in mesencephalus. Na+,K(+)-ATPase increase by acute DMI was inhibited when
      endogenous NA was depleted by the noradrenergic neurotoxin DSP-4 or the NA
      synthesis inhibitor alpha-methyl-p-tyrosine. On the whole, Mg(2+)-ATPase activity
      was not modified by treatment. 5'-nucleotidase, another membrane-bound enzyme,
      was unchanged by acute DMI. The addition of DMI in vitro (50 ng/mg tissue) during
      Na+,K(+)-ATPase assay failed to affect ATPase activities. Acute DMI effects on
      Na+,K(+)-ATPase are thus attributable to noradrenergic neurotransmission rather
      than to non-specific drug-CNS membrane interaction. Furthermore, DMI produces
      differential effects on membrane Na+,K(+)-ATPase, depending on treatment
      conditions and CNS area studied.

PMID- 8130741
TI  - Case management enhances long-term care insurance.

PMID- 8130742
TI  - Case management for special populations. Moving beyond categorical distinctions.
AB  - Case management has evolved as a flexible, pragmatic, and compassionate strategy
      for improving client access and care continuity within fragmented systems of
      health and social services. The first-generation case management programs have
      been designed for various settings that serve different "target" populations with
      varying social, medical, and psychological needs. This proliferation of
      categorical case management programs is a mixed blessing. While a categorical
      focus reflects both historical and public financing priorities, it creates a
      potentially duplicative and inefficient system in an era of limited resources. As
      the federal government assumes a more substantial role in supporting case
      management, greater attention is being given to accountability--demonstrating
      value-added benefits and identifying best practices for structuring case
      management. The essential first step is reaching agreement on two critical
      dimensions of case management, major goals and essential services. This article,
      based on a review of the literature, examines the extent to which seemingly
      disparate programs for special populations share common attributes, and thus
      present opportunities for structuring client-focused rather than categorical case
      management programs. The authors seek to stimulate a dialogue that would lead to
      specification of common goals and essential services, and a cross-cutting
      framework for designing client-focused case management programs.

PMID- 8130743
TI  - Case management. A comparative analysis of the United States and Great Britain.
AB  - With the pronounced growth in long-term care in the United States and Great
      Britain over the last two decades, there has been a quantitative move away from
      institutional care to community-based home care. This growth has pushed public
      funding and the delivery of social and health services in the two countries to
      the limits. This article presents a comparative analysis of the case management
      systems as they relate to long-term care in both countries. We also make
      recommendations to strengthen both countries' case management systems.

PMID- 8130744
TI  - Family caregivers as case managers. A statewide model for enhancing consumer
      choice.
AB  - Families spend considerably more time caring for their relatives than service
      providers do. Most family caregivers of persons with dementing illnesses express
      a strong preference to be their own case managers. This article describes the
      history, philosophy, and service components of a model statewide system of
      caregiver resource centers serving families and caregivers of cognitively
      impaired adults in California. An overview of the population served and salient
      characteristics is provided. California's Caregiver Resource Center system
      utilizes a philosophy of service planning, coordination, and delivery that is
      unusual among publicly funded programs in the United States: It seeks to give
      caregivers the specialized information, support and training to enable them to
      become their own case managers for their loved ones. Vesting authority about care
      decisions with the caregiver is considered central to the implementation of this
      innovative family support system.

PMID- 8130745
TI  - Evaluation of intensive case management for seriously and persistently mentally
      ill persons.
AB  - Case management and continuity of care have been an integral part of the
      community mental health movement since its inception in the United States in
      1963. The application of these concepts in treating the seriously and
      persistently mentally ill has, however, undergone continuous change. The most
      recent application is called intensive case management. In this article,
      preliminary findings from a 3-year evaluation of intensive case management
      programs in two Pennsylvania community mental health agencies are discussed.
      Results show only limited improvement in client level of functioning, but
      substantial desired change occurred in treatment utilization patterns and reduced
      cost of care.

PMID- 8130746
TI  - Case management services and long-term care insurance benefits.
AB  - Early versions of long-term care insurance were medically driven and
      institutionally biased. By design, these policies discouraged inappropriate or
      ineffective use of covered services. Newer long-term care policies have sought to
      meet policyholders' needs for greater flexibility in covered services and
      eligibility requirements. While significantly increasing the sales potential of
      these policies, this flexibility also means that insurers now must find a way to
      ensure that services are used appropriately and cost-effectively. One experienced
      provider of this "gatekeeping" service is the case management system.

PMID- 8130747
TI  - Educating case managers about elder abuse and neglect.
AB  - A recent study of clients referred to an intensive case management program,
      revealed that a substantial number had experienced physical and sexual abuse
      which was previously undetected because they were not asked about such
      experiences. This article describes the development, implementation, and
      evaluation of an elder abuse and neglect prevention program in Florida, a state
      estimated to have over 90,000 maltreated elders. Mean scores on an instrument
      administered to the 142 participants before and after the program indicated that
      case managers showed the most improvement among the various occupational groups.
      The findings point to the continuing need for educational programming, as
      evidenced not only by pretest scores but by the fact that almost one-fifth of the
      participants initially failed to even recognize that there was mandatory
      reporting of elder maltreatment in the state in which they worked.

PMID- 8130748
TI  - Generalist model of case management practice.
AB  - There has been a renewed interest during the past few decades in formalizing the
      use of case management in the fields of education, health, mental health, and
      human services. This article presents a generalist model of case management
      practice including 11 functions that are performed by case managers in many
      settings where case management is practiced. Several factors suggest that in the
      future the role played by case managers will become increasingly significant in
      assuring that clients receive quality services. The forces of program
      accountability, resource limitations, and client demands for services will
      intensify the need for developing case management practice models.

PMID- 8130749
TI  - International trends in long-term care case management.

PMID- 8130750
TI  - Case management in social and health care. Lessons from a United Kingdom program.
AB  - In the United Kingdom, despite a stated commitment to community care, centralized
      planning and financing through the Social Security System, rather than the Social
      Services Department, resulted in a serious distortion in policy. Social Security
      funded care in residential and nursing homes, and not community care. As in the
      United States, central government expenditures for expensive institutional care
      rose dramatically in the 1980s as a result. By the end of the decade, changes
      were implemented to decentralize the provision and funding of social care.
      Several projects were undertaken to demonstrate effective means of applying the
      new policies. In each instance, case managers worked with relatively small
      caseloads of the frail elderly and were responsible for allocating funds to
      purchase the services needed within a fixed budget. In all settings, there was a
      reduction in the use of institutional care facilities; the quality of life of
      both the clients and their caregivers improved significantly; and these gains
      were achieved at no greater cost than for individuals receiving the traditional
      services without case management. Despite the fact that issues such as what
      happens to costs when the system is expanded to other target clienteles remain to
      be resolved, the success of the projects highlights the significant gains to be
      achieved with case managers who have control of both service selection and
      budgets.

PMID- 8130751
TI  - Evaluation of an intensive case management program for short-term nursing home
      residents.
AB  - This study examines the impact of intensive case management services on nursing
      home length of stay and use of community-based resources for short-term nursing
      home residents. The findings did not reveal statistically significant effects,
      indicating that the outcomes of the services provided by the nursing home social
      workers and the intensive case managers were essentially the same. Discussion
      focuses on additional variables, such as rural/urban location and social
      service/nursing home staff relationships that may impact on the effects of case
      management on the discharge process.

PMID- 8130752
TI  - Case management in mental health. The pendulum still swings.
AB  - This article surveys the practice of case management in mental health treatment
      both historically and in its current form. Case management, along with mental
      health treatment in the United States, is a pendulum that swings in the motion of
      prevailing societal values, monetary considerations, and problem-solving
      philosophies. It is unclear whether case management services are solving the
      problems they target, nor can we determine just how long it might take for the
      pendulum to swing from community care back to institutional settings.

PMID- 8130753
TI  - Ventricular late potentials. Part II. Clinical importance and interpretation.
AB  - This second part of a review on the ventricular late potentials (VLP) includes
      most of the latest data on their clinical interpretation. A description of VLP
      characteristics in normal subjects is followed by an analysis of their
      significance in several cardiovascular diseases in which VLP presence has been
      almost currently investigated, i.e., acute myocardial infarction, postinfarction
      states, unexplained syncopes, cardiomyopathies and post-heart surgery states.
      Particular situations such as the congenital or acquired syndrome of long QT and
      VLP incidence, bundle branch blocks and VLP presence, the effect on the VLP of
      some anti-arrhythmogenic blockers of sodium channels are further discussed. Up to
      date information on the VLP significance in cardiovascular pathology and the
      author's personal experience on the VLP significance in patients with ischemic
      heart disease, syncopes, dilating cardiomyopathies or long QT interval are
      presented.

PMID- 8130754
TI  - Doppler echocardiographic parameters of evaluation of left ventricular systolic
      function.
AB  - The authors suggest a new method using Doppler echocardiography for the
      evaluation of cardiac performance. Doppler echocardiography permits the
      calculation of left ventricular (LV) ejection force (according to Newton's second
      law of motion). The ejection force was calculated in 36 patients with heart
      failure subgrouped into 3 groups based on ejection fraction (EF) (> 60%; 41-60%;
      < 40%) compared to 11 normal subjects. The LV ejection force showed a good linear
      correlation with LV ejection fraction (r = 0.86). Data of the study suggest that
      the LV ejection force is a valuable and accurate index for the assessment of
      cardiac performance, especially in early stages of disease.

PMID- 8130755
TI  - Chronotropic response during exercise testing in old people.
AB  - The possibility of a depressed chronotropic response to exercise in old people as
      an early signs of sinus node disfunction, was studied in 118 subjects over 60
      years (group A) and 25 subjects under 60 years (group B), subjected to a maximal,
      symptom limited, exercise test (ET) using a cycloergometer. There were no
      significant statistical differences between the two groups as regards the heart
      rate (HR) at rest, increase of HR at each effort level, and mean chronotropic
      impairment (Chl). The mean values were the same when the subjects over 65 years
      were considered separately (group C). But, when the chronotropic response to ET
      was studied individually, it was depressed (HR increment less than 15 beats/min
      at each level) in 22.3% of subjects in group A and only in 4% in group B. The
      depression was important (increment less than 10/min) in 15% of the subjects in
      group A and in none of those in group B. The results suggested that about 1/4 of
      the old people have depressed chronotropic response to exercise attributed by us
      to a subclinical sinus node disfunction.

PMID- 8130756
TI  - Plasminogen activator inhibitor (PAI) in obese men and obese women.
AB  - When compared to plasma PAI activity noted in selected control normal-weight
      normolipidemic women (9.36 AU/ml +/- 1.2) and men (13.6 AU/ml +/- 1.96), this
      inhibitor of fibrinolysis was found to be significantly (p < 0.001) higher in
      gender-matched obese patients. Obese men younger than 45 years, however,
      displayed a plasma PAI activity (32.5 AU/ml +/- 5.45) significantly higher (p <
      0.01) than that recorded in age-matched obese women (17.8 AU/ml +/- 2.25). No
      significant difference concerning PAI activity was noted between women older than
      45 years (26.4 AU/ml +/- 3.66) and age-matched men (23.8 AU/ml +/- 3.29). High
      plasma PAI activity was accompanied by an increased resistance of plasma clots to
      exogenous t-PA induced fibrinolysis. Since PAI depleted plasma clots however
      displayed a weak resistance to t-PA induced fibrinolysis, it was concluded that
      plasma PAI may be the main, but not the only factor, responsible for the
      prolonged plasma clot lysis time in obese subjects.

PMID- 8130757
TI  - Circulating immune complexes and low density lipoproteins--a molecular complex or
      the summation of the atherogenic risk of two separate entities?
AB  - The correlation between the circulating immune complexes (CIC) and dyslipidemia
      was studied in a group of 150 patients with acute ischemic stroke and 50 normal
      controls. The object of the study was also to find out whether these two
      components represent a macromolecular complex with increased atherogenic capacity
      or only two risk factors acting separately but achieving a summation of their
      atherogenic power. It can be considered that in acute ischemic stroke the
      presence of the two risk factors constitutes a condition of acceleration of the
      atherogenic process, i.e., the appearance of the vascular accident. The decrease
      of HDL-cholesterol detected in all the subgroups studied is probably due to the
      decrease of the cholesterol "reverse transport" process which favours the
      atherogenic process. It was found that CIC and low density lipoproteins (LDL) are
      risk factors which act separately determining by the effects they generate a
      summation of their atherogenic capacity. Cholesterol and triglycerides apparently
      contained in the CIC structure, can be considered as a methodologic artefact due
      to the use of a common reagent (PEG-6000).

PMID- 8130758
TI  - Introduction to the study of adult T-cell leukemia and HTLV-I sero-positivity in
      Romania.
AB  - The study presents 6 cases of leukemia/lymphoma (with mature T-cells)
      corresponding to the diagnostic criteria of adult T-cell leukemia (ATL): adult
      age onset of leukemia/lymphoma, organomegaly but normal mediastinum, leukemic
      cells with typical morphology and phenotype hypercalcemia. The evolution of
      disease was severe of subacute with resistance or partial response to therapy.
      The virologic assays were positive according to the ELISA test in four cases of
      which two presented, according to the Western blot assay, HTLV-I infection. The
      epidemic aspect of this infection is discussed as well as the possibility of
      contamination and the geographic spread of the places of origin of the patients.
      Emphasis is laid on the young age (22-26 years) of three of the patients
      infected, as a peculiar feature of the disease in Romania.

PMID- 8130759
TI  - Tumoral infiltrate after local treatment with interferon in squamous cell
      carcinoma.
AB  - Using monoclonal antibodies UCHL-1 (T lymphocytes), MT-1 (pan T) and L-26 (B
      lymphocytes) in the study of the tumoral infiltrate after local treatment with
      alpha interferon (Roferon) in patients with squamous cell carcinoma of the lower
      lip, it was observed that: the proportion of UCHL-1 positive cells was between
      30% and 80%, the proportion of MT-1 positive cells was of 85% and that of the L
      26 positive cells was of 30% of all the cells in the infiltrate. In the area in
      which after treatment with interferon the tumoral structures had disappeared, the
      proportion of T lymphocytes was smaller than in the areas in which the tumoral
      structures were still present. The therapeutic effect of interferon is due both
      to the direct effects on the tumoral cell and also to the indirect effects,
      namely the activation of the cytotoxic T lymphocytes and of other cells in the
      tumoral infiltrate.

PMID- 8130760
TI  - Diabetic gangrene: medical and surgical causes and consequences.
AB  - Diabetic gangrene is the chronic complication which involves many medical,
      economic and social problems. In this study we have analyzed the medical and
      surgical causes and consequences of diabetic gangrene on three groups of
      patients: 120 patients (96 males and 24 females; aged (X +/- SD) 57 +/- 14 years
      hospitalised in the Clinic of Diabetes, Nutrition and Metabolic Diseases of the
      "N. Paulescu" Institute, 72 patients (59 males and 13 females; mean age 60 +/- 10
      years) hospitalised in the Surgical Clinic of Cantacuzino Hospital; 29 patients
      (23 males and 6 females; mean age 58 +/- 11 years) hospitalised in the
      Cardiovascular Department of Fundeni Hospital. The analyses of data obtained
      showed: in 77% of cases the initial lesions might have been avoided by an
      appropriate education programme of the patients; in 66% of cases the progression
      of lesion from medical to surgical stage was caused by tardily coming of patient
      to physician; average duration of hospitalization was 27 days in the Clinic of
      Diabetes, Nutrition and Metabolic Diseases, 33 days in the Clinic of Surgery of
      "Cantacuzino" Hospital and 25 days in Cardiovascular Department of Fundeni
      Hospital; the surgical mortality was 8%; 47% operated patients were cured and 53%
      were incompletely cured and required more out patient care; 35% were thigh
      amputations, that shows the high invalidity potential of diabetic gangrene; the
      cost of medical and/or surgical care of diabetic gangrene is higher than the cost
      of hospitalisation for other patients; the diabetic gangrene predominantly
      neuropathic was better cured and the arteriopathic component breaks the medical
      curing and impose high amputations; diabetic gangrene is more frequent with older
      people, but with young people it is a cause of early retiring and psycho-social
      concern.

PMID- 8130761
TI  - The relationship between aminoaciduria and plasma hemoglobin levels.
AB  - Investigations in newborns, children and young adults have revealed an inverse
      proportion between aminoaciduria and plasma hemoglobin (Hb) levels. Values above
      normal were recorded for alanine, leucine, valine, phenylalanine and glutamic
      acid, correlating proportionally with their increased blood levels, and preceding
      or being concomitant with the decrease of plasma Hb, both during the first 20
      months of life and in young adults. The return to near normal values of
      aminoaciduria occurred generally only after an early treatment with minerals,
      vitamins and trace elements (Supradyn), activators of the enzymes involved in the
      amino acid metabolism. After treatment, the Hb levels also became almost normal.
      An early re-equilibration of the amino acid metabolism can prevent the risk of
      developing, at the adult age, certain anemias and other diseases (rachitism,
      mental handicap, urinary infections, conjunctivitis, stomatitis, a.o.). The
      correlation factor was r = 0.964 and the differences between the data recorded in
      patients and in controls were statistically significant (p < 0.01).

PMID- 8130762
TI  - Pharmaceutical and Biomedical Analysis Meeting. Utrecht, The Netherlands, 26
      November 1994. Abstracts.

PMID- 8130763
TI  - Drug Treatment in the Elderly. Meeting of the European Society of Clinical
      Pharmacy Special Interest Group on Geriatrics. Leysin, Switzerland, 10-12 March
      1994. Abstracts.

PMID- 8130764
TI  - Sodium dodecyl sulfate-polyacrylamide solution-filled capillary electrophoresis
      of proteins using stable linear polyacrylamide-coated capillary.
AB  - Sodium dodecyl sulfate (SDS)-linear polyacrylamide solution-filled capillary
      electrophoresis using a stable coated fused silica capillary has been developed
      for the separation and molecular weight determination of proteins. A fused silica
      capillary was coated with linear polyacrylamide through Si-C bond which
      suppressed the electro-osmotic flow and reduced the adsorption of proteins.
      Acrylamide solution containing SDS was filled into the coated capillary and
      polymerized. Compared with a conventional fused silica capillary coated with 3
      methacryloxypropyltrimethoxysilane through siloxane linkage (Si-O-Si-C), the
      developed capillary was much more stable, even in the alkaline condition.
      Consequently, the durability of the polymer matrices and the reproducibility of
      separation were markedly improved. An excellent linear relationship was obtained
      between the mobility and the logarithm of the protein molecular weight. The
      relative standard deviation of migration times was below 1%.

PMID- 8130765
TI  - Determination of the molecular-weight distribution of low-molecular-weight
      heparins using high-performance gel permeation chromatography.
AB  - The molecular-weight distribution of commercially available low-molecular-weight
      heparins (LMWHs) was estimated by high-performance gel permeation chromatography
      (HPGPC) using a LMWH molecular-weight calibrant, supplied by the National
      Institute for Biological Standards and Control for the calibration of columns.
      This calibrant is a mixture of many polysaccharides with a disaccharide unit
      prepared by a random depolymerization of unfractionated heparin, and the ends of
      the fragments have a UV absorption. The ratio of the refractive index to the UV
      absorption is a relative measure of molecular weight. Various molecular-weight
      parameters such as weight-, number- or z-average molecular-weights,
      polydispersity and relative distributions of high, middle and low molecular
      weight components were estimated, indicating that LMWHs have a wide variation in
      molecular-weight distribution. This variation was ascribed to the difference in
      preparation methods from unfractionated heparins.

PMID- 8130766
TI  - Dietary manipulation by perilla oil and fish oil of hepatic lipids and its
      influence on peroxisomal beta-oxidation and serum lipids in rat and mouse.
AB  - Rats and mice were fed a diet, prepared with soybean oil (SO), perilla oil (PO)
      or fish oil (FO), for 4 weeks. Compared with the groups of SO-feeding, FO-feeding
      increased content of eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid
      (22:5 n-3) and docosahexaenoic acid (22:6 n-3) and PO-feeding elevated the
      content of alpha-linolenic acid (18:3 n-3), 20:5 n-3 and 22:5 n-3 or hepatic
      lipids of both rats and mice. FO-feeding increased the activity of peroxisomal
      beta-oxidation in the livers of both rats and mice. The activities of peroxisomal
      beta-oxidation in rats and mice that were fed FO diet at a high fat (40% of
      energy) concentration corresponded to 20% and 30%, respectively, of the maximum
      activities induced by peroxisome proliferators (4-chlorophenoxyisobutyric acid or
      perfluorooctanoic acid). To a lesser extent, PO-feeding elevated this activity
      too. There were significant correlations between peroxisomal beta-oxidation
      activity and the content of either 20:5 n-3, 22:5 n-3 or 22:6 n-3 in hepatic
      lipids. FO-feeding decreased effectively serum level of cholesterol of both rats
      and mice. The reduction in serum cholesterol by feeding PO was less pronounced
      than that observed with FO-feeding. A high correlation was found between 22:6 n-3
      content in hepatic lipids and serum concentration of cholesterol. Although FO
      feeding lowered the level of circulating triacylglycerol, PO-feeding produced no
      change. No substantial correlation was observed between the hepatic content of n
      3 fatty acid and the concentration of serum triacylglycerol.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8130767
TI  - Gene structure of bovine adrenodoxin reductase.
AB  - The gene structure of bovine adrenodoxin reductase, a component of the
      mitochondrial steroid hydroxylating system in the adrenal cortex, was determined.
      When we screened a bovine genomic DNA library, using bovine adrenodoxin reductase
      cDNA as a probe, we isolated 10 genomic clones covering a continuous 30 kilobase
      (kb) region of bovine chromosomal DNA in which the adrenodoxin reductase gene
      spanned approximately 12 kb. The adrenodoxin reductase gene consisted of 12 exons
      and all the donor and acceptor sites of the exon/intron junction followed the
      GT/AG rule. The transcription initiation site was found to be 79 bases upstream
      of the translation initiation site by primer extension analysis and putative CAAT
      and GC boxes, but no typical TATA box, were present in the 5'-flanking region.
      The 5'-flanking region of this gene showed several features characteristic of
      promoters of house-keeping genes. The CCAGGG sequence present in the 5'-flanking
      region of genes for adrenodoxin and the steroid hydroxylating cytochromes P-450
      in the adrenal cortex was present 13 bases upstream from the transcription
      initiation site. We analyzed the promoter activity of the 5'-upstream region of
      this gene, using as a reporter the chloramphenicol acetyltransferase gene. The
      region between position -757 to -376 was proved necessary for expression of this
      gene in mouse Y-1 tumor cells. Adrenocorticotropin did not enhance the expression
      of this bovine gene in the cells.

PMID- 8130768
TI  - Characterization of a neutral and an acidic polysaccharide having immunological
      activities from the root of Paeonia lactiflora.
AB  - A neutral and an acidic polysaccharide, called peonan SA and peonan SB, were
      isolated from the root of Paeonia lactiflora Pallas. They were homogeneous on
      electrophoresis and gel chromatography, and their molecular masses were estimated
      to be 11.2 x 10(4) and 25.0 x 10(4), respectively. Peonan SA is composed of L
      arabinose: D-galactose: D-glucose in the molar ratio of 1:1:28, and peonan SB is
      composed of L-arabinose: D-galactose: D-galacturonic acid in the molar ratio of
      4:3:2, in addition to small amounts of peptide moieties. About forty percent of
      the hexuronic acid residues in peonan SB exist as methyl esters. Reduction of
      carboxyl groups, methylation analysis, nuclear magnetic resonance and periodate
      oxidation studies indicated that their structural features include mainly 3,4-
      and 4,6-branched alpha-D-glucan type units (peonan SA) and principally alpha-1,5
      linked L-arabino-beta-3,6-branched D-galactan type structural units (peonan SB).
      Both polysaccharides, especially in peonan SB, showed remarkable
      reticuloendothelial system-potentiating activity in a carbon clearance test and
      considerable anti-complementary activity.

PMID- 8130769
TI  - Enzymatic formation of D-cysteinolic acid conjugated chenodeoxycholic acid in
      liver preparation from red seabream, Pagrosomus major.
AB  - The enzymatic formation of D-cysteinolic acid conjugated chenodeoxycholic acid in
      liver preparation from a marine teleost, wild and cultured red seabream,
      Pagrosomus major, was investigated. [24-14C]Chenodeoxycholic acid was incubated
      with taurine, glycine, or D-cysteinolic acid in the liver preparation in the
      presence of CoA, ATP, NAD+ and FAD. D-Cysteinolic acid could be conjugated
      efficiently with chenodeoxycholic acid to give chenodeoxycholyl-D-cysteinolic
      acid in both wild and cultured red seabream liver preparations, though the
      production rate was slower than that of the formation of chenodeoxycholyltaurine.
      Under the conditions employed, glycine was not utilized as the substrate for the
      conjugation at all. The formation of chenodeoxycholyl-D-cystenolic acid was
      decreased by the addition of various concentrations of taurine to the incubation
      mixture. These results suggest that bile acid-CoA: amino acid N-acyltransferase
      in red seabream is not able to distinguish taurine and D-cysteinolic acid as the
      substrate, probably because of their structural similarity. Consequently, D
      cystenolic acid conjugated bile acids found in the bile of wild red seabream were
      thought to be synthesized in the liver of the fish utilizing the unusual amino
      acid, which originated from foods, prior to secretion into the bile.

PMID- 8130770
TI  - Effects of ecabet sodium (TA-2711), a new antiulcer agent, on gastrointestinal
      mucosal prostanoid production and morphology in rats.
AB  - Effects of ecabet sodium (TA-2711), a locally acting antiulcer agent, on
      prostanoid production and the morphology of the rat gastrointestinal mucosa were
      studied in comparison with sucralfate. Ecabet, at therapeutic doses (25 and 100
      mg/kg, p.o.), dose-dependently increased the gastric mucosal level of
      prostaglandin E2 (PGE2): sucralfate (100 mg/kg, p.o.) showed a tendency to
      increase the PGE2 level. In an ex vivo study, ecabet (25 and 100 mg/kg, p.o.)
      dose-dependently increased the capacity of the gastric mucosa to synthesize PGE2
      and PGI2 without modifying tromboxane A2 (TXA2) synthesis, and the 100 mg/kg dose
      persisted for up to 3 h. Ecabet (400 mg/kg, p.o.) also significantly increased
      PGE2 synthesis and there was a tendency to increase PGI2 synthesis by the
      duodenal mucosa, without affecting TXA2 synthesis. PGE2 synthesis by the colonic
      mucosa was not affected, even at a high dose of ecabet (1000 mg/kg, p.o.). When
      the rat gastric mucosa was examined by light microscopy and scanning electron
      microscopy, ecabet (100 and 400 mg/kg, p.o.) had caused no morphological change
      to the gastric mucosa, while sucralfate (100 and 400 mg/kg, p.o.) produced apical
      rupture of the epithelial cells and subepithelial edema. The present study
      indicates that ecabet locally stimulates PGE2 and PGI2 production in the
      gastroduodenal mucosa and this effect is not attributable to a local irritant
      action accompanied by superficial epithelium damage.

PMID- 8130771
TI  - Effects of intravenous anesthetics, thiopental, fentanyl, and morphine on
      ventricular delayed activation in a canine myocardial infarction model.
AB  - We examined the effects of intravenous anesthetics (thiopental, fentanyl and
      morphine) on the ventricular activation in a canine myocardial infarction model.
      Thiopental at 5 and 10 mg/kg delayed or abolished the delayed activation in the
      infarcted zones with slight delay of activation of the normal zones. Fentanyl at
      30 micrograms/kg slightly but significantly prolonged the activation time in both
      normal and infarcted zones. Morphine at 1 mg/kg did not produce any significant
      effect. Thiopental, but neither fentanyl nor morphine, inhibited ventricular
      stimulation-induced arrhythmias. Thus, thiopental, but not fentanyl nor morphine,
      markedly depressed the delayed activation in myocardial infarction, which may
      affect and probably inhibits the ventricular arrhythmias in myocardial
      infarction. It also should be kept in mind that thiopental may have
      arrhythmogenic effects in myocardial infarction.

PMID- 8130772
TI  - Diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel
      adenosine A1 receptor antagonist, in conscious dogs.
AB  - The diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a
      novel adenosine A1 receptor antagonist, were determined and compared with those
      of trichlormethiazide (TCM) and furosemide in saline-loaded conscious dogs. KW
      3902, at doses higher than 0.1 mg/kg (p.o.), produced dose-dependent increases of
      urine volume and sodium excretion and these effects were statistically
      significant at doses of 1-100 mg/kg. The increase in potassium excretion was
      lower than that of sodium, and the ratio of sodium to potassium excretion (Na/K)
      tended to be elevated. TCM (0.3 mg/kg) and furosemide (3 mg/kg) also induced
      increases in urine volume and sodium excretion. The diuretic effects of KW-3902
      lasted for 4 h after administration, whereas TCM and furosemide caused
      significant natriuresis for 2 h after administration. Thus, KW-3902 exhibited a
      longer lasting natriuresis than TCM and furosemide. These results indicate that
      adenosine A1 receptor blockade by KW-3902 causes consistent diuresis and
      natriuresis in dogs and suggest that adenosine A1 receptor blockade is a
      promising approach to diuretic therapy.

PMID- 8130773
TI  - Carbonic anhydrase activators. VII. Isozyme II activation by bisazolyl-methanes, 
      ethanes and related azoles.
AB  - A correlation was found between the carbonic anhydrase II activating power and
      the pKa values for a series of azoles, bisazolylmethanes and bisazolylethanes.
      Strong activations were found for compounds with pKa's in the interval 6.5-8.0.
      The mechanism of action for such activators is discussed.

PMID- 8130774
TI  - Modulation of ethanol-mediated CYP2E1 induction by clofibrate and L-carnitine in
      rat liver.
AB  - To understand the effects of lipid-lowering agents on the ethanol-induction of
      hepatic CYP2E1, clofibrate and L-carnitine were administered to adult male rats.
      The administration of ethanol in the diet (containing 21% calories as ethanol,
      given for 3 weeks) increased levels of hepatic CYP2E1 protein (1.9-fold that of
      untreated controls) and mRNA (2.1-fold). In contrast, the administration of
      clofibrate (0.1%v/v) in an ethanol-containing diet did not significantly increase
      either CYP2E1 protein (1.1-fold) or mRNA (0.8-fold), in spite of the significant
      increases in blood ketone bodies. Administration of L-carnitine alone had no
      clear effect on CYP2E1 and blood ketone body levels. Co-administration of L
      carnitine, however, increased liver microsomal CYP2E1 protein (2.5-fold) in rats
      given an ethanol-containing diet. No difference was observed in the mRNA levels
      in rats receiving ethanol with and without L-carnitine. These results indicate
      that clofibrate and L-carnitine modulate ethanol-mediated induction of hepatic
      CYP2E1 independent of blood levels of ketone bodies. It is also suggested that
      these lipid-lowering agents affected hepatic CYP2E1 through particular
      mechanisms, suppression of the specific mRNA and post-translation stabilization.

PMID- 8130775
TI  - Photodynamic DNA strand breaking activities of acridine compounds.
AB  - Induction of single strand breaks in DNA was assessed by the conversion of
      supercoiled closed circular plasmid DNA into the open circular form. Euflavine
      produced single-strand breaks following irradiation but not in the control
      maintained in the dark. The single strand breaking activity of photoactivated
      euflavine was found to be dose-dependent. The effective dose conversion 50%
      (ED50) of the closed circular DNA to the open circular form was 0.53 microM. A
      comparison of 8 acridine compounds revealed that the ED50 of diaminoacridines
      such as euflavine, proflavine and acridine yellow or the 3,6-dimethylamino
      derivative (acridine orange) was less than 1 microM while the ED50 values of the
      other acridines were greater than 80 microM. Euflavine was markedly inhibited by
      singlet oxygen scavengers such as NaN3, histidine, alpha-tocopherol or beta
      carotene and partly inhibited by superoxide dismutase, mannitol or catalase.
      These results suggest that enflavine induces single strand breaks in DNA mainly
      by a type II photodynamic mechanism. Photodynamic single strand breaking
      activities appeared related to their mutagenic activities on yeast. This
      experimental system described here is useful for the quantitative assessment of
      the single strand breaking activities of various photosensitizers in vitro and
      for the determination of active oxygen species involved in those processes.

PMID- 8130776
TI  - Inhibition of the induction and activity of hepatic P450IA isozymes by in vivo
      administration of carbon tetrachloride to rats.
AB  - The effect of carbon tetrachloride (CCl4) on the induction and activity of 3
      methylcholanthrene (MC)-inducible P450IA isozymes (P450IA1 and P450IA2) in the
      liver was examined by treating male Sprague-Dawley rats with simultaneous i.p.
      injections of MC and CCl4. Following the treatment, the quantities of P450IA
      mRNAs determined by Northern blotting and P450IA proteins by Western blotting
      were significantly reduced as compared with those in rats treated with MC alone.
      As determined by a bacterial mutation test using carcinogenic aromatic amines are
      P450IA enzyme substrates, CCl4 treatment selectively inhibited the activity of
      P450IA2 in the MC-induced isozymes. These results indicate that CCl4 exerts on
      inhibitory effect on the induction of P4501A isozymes and that it selectively
      inhibits P450IA2 activity.

PMID- 8130777
TI  - Evaluation of enteric coated tablet sensitive to pancreatic lipase. II. In vivo
      evaluation.
AB  - Plain tablets containing a model drug, sulfamethizole (SMZ), were coated with
      triolein (TO), trilaurin (TL) and ethylcellulose (EC). The biological behavior of
      the coated tablets (TOTL-Tab), which are pH independent and sensitive to
      pancreatic lipase, was investigated in humans. Results of the administration of
      the tablets with or without an antacid, under fasting and non-fasting conditions,
      and at 0.5 h before and 0.5 h after meals, were examined. A comparison of the in
      vivo behavior of SMZ after the administration of these tablets was done using the
      following data: the lag time of urinary excretion (Ulag), the total urinary
      recovery percentage (X infinity u), and the mean residence time after Ulag
      (MRTaf). A typical pH-sensitive tablet coated by cellulose acetate phthalate (CAP
      Tab) was used as a reference. For the administration of a CAP-Tab alone, the Ulag
      obtained under both the non-fasting and fasting condition was longer than that of
      the plain tablet. However, Ulag after the administration of a CAP-Tab with an
      antacid became considerably shorter. This lag time was about the same as that
      obtained from the plain tablet, regardless of food ingestion. The obtained CAP
      Tab MRTaf and X infinity u values were not significantly different in comparison
      to the plain tablets. Under the non-fasting condition, Ulag, MRTaf and X infinity
      u of TOTL-Tab were not affected by the co-administration of an antacid, and these
      values were virtually the same as those obtained from a CAP-Tab without an
      antacid. The urinary excretion data obtained after the administration of TOTL-Tab
      alone under fasting was analogues to the non-fasting case.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8130778
TI  - The disposition of serum proteins as drug-carriers in mice bearing Sarcoma 180.
AB  - The tumor distribution and the disposition of serum proteins, such as albumin,
      fetuin, transferrin, and IgG, were investigated in mice bearing Sarcoma 180.
      Serum proteins labeled with fluoresceinisothiocyanate (FITC) were administered to
      the mice. The FITC-labeled proteins acylated with glutaric anhydride were also
      administered to the mice in order to investigate the effect of chemical
      modification. The plasma concentration of each glutarylated serum protein was
      significantly lower, about 15 to 46-fold, in comparison to that of the non
      acylated protein at 24 h after administration. The tissue distributions of the
      glutarylated serum proteins were also decreased compared to those of the non
      acylated proteins. Especially, the hepatic distribution of albumin and IgG was
      significantly reduced with glutarylation. The urinary excretion of albumin and
      transferrin, and fecal excretion of IgG, were significantly increased with
      glutarylation. The serum proteins were accumulated effectively in the tumor
      tissue in mice bearing Sarcoma 180. It was found that the tumor distributions
      were not impaired by the glutarylation, except involving fetuin. It was
      suggested, therefore, that the glutarylated serum proteins were valuable for
      relative tumor-selectivity and might be utilized in a macromolecular carrier
      system for antitumor drugs.

PMID- 8130779
TI  - Pharmacokinetics of cyproheptadine and its metabolites in rats.
AB  - To investigate the pharmacokinetics of cyproheptadine (CPH) and its metabolites,
      the plasma concentration and urinary excretion of CPH and its detectable
      metabolites were determined after intravenous (i.v.) administration of parent or
      synthesized metabolites to rats. The plasma CPH concentration-time course was
      subjected to biexponential calculation following the i.v. administration of CPH,
      producing the temporal and low plasma concentrations of desmethylcyproheptadine
      (DMCPH) and the sustained plasma concentrations of desmethylcyproheptadine
      epoxide (DMCPHepo). DMCPH was also eliminated, according to the biexponential
      equation, after i.v. administration of performed DMCPH, forming DMCPHepo in
      plasma. On the other hand, no detectable DMCPHepo was found in plasma after the
      i.v. administration of cyproheptadine epoxide (CPHepo). All compounds
      administered had large distribution volumes and were almost entirely excreted as
      DMCPHepo in urine; this excretion continued for a long time. However, the urinary
      excretion pattern of DMCPHepo after CPHepo was different from those after CPH and
      DMCPH. The mean residence times of the epoxidized metabolites estimated from the
      urinary data were much longer than those from the plasma concentration data,
      suggesting either a gradual reflux of the metabolites from a tissue depot into
      systemic circulation under those plasma concentrations close of detection limit,
      or some interaction which delays excretion into the urine. This study suggests
      that both metabolic pathways of CPH, through DMCPH and CPHepo, to DMCPHepo are
      possible, but that the demethylation of CPH largely occurs prior to epoxidation;
      also that the extensive and persistent distribution of DMCPHepo to tissues may
      relate to the toxicity of CPH reported in rats.

PMID- 8130780
TI  - An increase of 63 kDa-protein present in the cell membranes of Staphylococcus
      aureus that bears a plasmid mediating inducible resistance to partial macrolide
      and streptogramin B antibiotics.
AB  - A plasmid, pEP2104 (23.9 kilobase pairs), from Staphylococcus aureus carries a
      gene that specifies inducible resistance to 14-membered (erythromycin, EM, and
      oleandomycin, OL) and 16-membered macrolide (mycinamicin I and II), but not to
      all of the latter, and to streptogramin type B antibiotics (partial macrolide-
      and streptogramin-B-antibiotic resistance: PMS-resistance) (L. Janosi, E. Ban,
      Acta Microbiol. Acad. Sci. Hung., 29, 187 (1982) and Y. Nakajima et al., J.
      Pharmacobio-Dyn., 15, 319 (1992)). The induced cells of strain 8325(pEP2104) did
      not inactivate EM, OL, josamycin, rokitamycin or mikamycin B (MKM-B), and the
      cell-free extract of the strain did not inactivate EM or MKM-B, either. Ribosomes
      from the cells whose PMS-resistance was induced by EM were sensitive not only to
      EM or spiramycin, but also to MKM-B. A 63000-dalton protein increased to a great
      extent only in the cell membrane fractions of induced 8325(pEP2104), and may be
      involved in PMS-resistance.

PMID- 8130781
TI  - Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of
      a polysaccharide from the cultural mycelium of Cordyceps sinensis.
AB  - Crude polysaccharides were obtained from a hot-water extract and alkaline
      extracts of the cultural mycelium of Cordyceps sinensis. They showed significant
      activity in normal mice and streptozotocin-induced diabetic mice as a result of
      intraperitoneal (i.p.) injection. A crude polysaccharide (CS-OHEP) obtained from
      5% sodium hydroxide extract slightly lowered the plasma glucose level in normal
      mice by oral (p.o.) administration. A neutral polysaccharide (CS-F30) exhibited
      higher hypoglycemic activity than its crude polysaccharide (CS-OHEP), exhibited
      by i.p. injection, and it significantly lowered the glucose level by p.o.
      administration (50 mg/kg). However, it hardly affected the plasma insulin level
      in normal mice. CS-F30 ([alpha]D + 21 degrees in water) is composed of galactose,
      glucose and mannose (molar percent, 62:28:10), and its molecular weight is about
      45000.

PMID- 8130782
TI  - Conformational changes in deoxyribonuclease I in anionic and cationic surfactant
      solutions.
AB  - The effect of sodium dodecylsulfate (SDS) and dodecyltrimethylammonium chloride
      (DTAC) on the conformation of bovine pancreatic deoxyribonuclease I (DNAse I, EC
      3.1.21.1) has been studied by using fluorescence and circular dichroism methods
      as a function of surfactant concentration. About 60% of the fluorescence was
      quenched in the presence of 1 mM SDS, indicating the partial conformational
      transition of DNase I; the conformational susceptibility of DNase I to SDS was
      reduced by Ca2+ ions. The free energy changes were evaluated at 4.0 +/- 0.1
      kcal.mol-1 in the presence of 5 mM Ca2+ ions and 2.5 +/- 0.1 kcal.mol-1 in the
      absence of Ca2+ ions. No fluorescence changes occurred in DTAC solution. The
      residue ellipticity of DNase I at 222 nm decreased in the presence of 1-1.4 mM
      SDS indicating degradation of the secondary structure of DNase I, while DTAC had
      not effect on the ellipticity at 222 nm, even in the presence of 10 mM DTAC. The
      enzymatic activity of DNase I was abolished by SDS, the deactivation profile
      being compatible with the fluorescence decay profile induced by SDS. On the other
      hand, no deactivation was induced by DTAC.

PMID- 8130783
TI  - Differential effects of acyclothymidine, a potent pyrimidine nucleoside
      phosphorylase inhibitor, on the pharmacokinetics of doxifluridine in rabbits via
      oral administration.
AB  - Acyclothymidine (AcyT, 5-methyl-1-(2'-hydroxyethoxymethyl)uracil), a potent
      inhibitor of pyrimidine nucleoside phosphorylase (PyNPase), was co-administered
      with 5'-deoxy-5-fluorouridine (5'-DFUR), a PyNPase activating prodrug of 5
      fluorouracil (5-FU), to rabbits. The absorption and pharmacokinetic parameters of
      5'-DFUR and its active metabolite 5-FU, after administration of 5'-DFUR in
      combination with AcyT, were evaluated in the animals. Animals were given an oral
      or intravenous administration of 5'-DFUR (50 mg/kg) in combination with an
      equimolar dose of AcyT (40 mg/kg). The half-lives (t1/2) of 5'-DFUR and 5-FU in
      plasma were 16.8 and 11.5 min, respectively. AUC (area under the plasma
      concentration-time curve) of 5'-DFUR and 5-FU following the oral administration
      of 5'-DFUR (50 mg/kg) was 1710 and 24.3 micrograms.min/ml, respectively. After
      the oral co-administration of 5'-DFUR and AcyT (at a molar ratio of 1:1), the AUC
      values for 5'-DFUR and 5-FU increased to 2680 and to 121.1 micrograms.min/ml,
      respectively. However, this combination had little effect on the t1/2 of 5'-DFUR.

PMID- 8130784
TI  - The first metatarsal bicorrectional head osteotomy (distal "L"/Reverdin-Laird
      procedure) for correction of hallux abducto valgus: a retrospective study.
AB  - A retrospective analysis of the distal "L" osteotomy with bunionectomy (Reverdin
      Laird procedure) for correction of hallux abducto valgus was performed. Sixty
      nine cases meeting strict eligibility and exclusion criteria underwent evaluation
      an average of 33.51 months after the procedure. The evaluation included
      radiographs, physical examination, patient survey, and medical record review. The
      average decreases in radiographic angles were as follows: Hallux abductus: 19.97
      degrees, relative intermetatarsal angle: 7.49 degrees, proximal articular set
      angle: 13.9 degrees. Twenty-seven cases demonstrated a negative proximal
      articular set angle. Only five of these cases resulted in clinical hallux varus.
      There was an average of 4.23 mm. of first metatarsal shortening with this
      procedure. Average postoperative range of motion of the first metatarsophalangeal
      joint was 72.05 degrees. The appearance of the forefoot was judged good or
      excellent in 91.3% of the surgeries. Hallux position was in rectus or mild
      abductus in 86.9% of cases. Complication rates included hallux varus,
      metatarsalgia, lesion subsecond metatarsophalangeal joint, pain at the surgical
      site, long-term stiffness, pin tract infection, and numbness. There were no cases
      of osteomyelitis or avascular necrosis. Survey results revealed a high level of
      patient satisfaction with this procedure (94.2%). Patient satisfaction was
      dependent on elimination of pain and ability to wear the desired shoe gear
      comfortably, not on hallux position.

PMID- 8130785
TI  - Pyoderma gangrenosum.
AB  - The authors present a case report of pyoderma gangrenosum. Antibiotics may be
      indicated, but are not curative. A review of the literature is also presented.

PMID- 8130786
TI  - The antiglide plate for the Danis-Weber type-B fibular fracture: a review of 71
      cases.
AB  - The authors present a retrospective study of 71 fractures seen in 70 patients who
      had sustained the Danis-Weber type-B fibular fracture. All patients had the
      fractures fixated with the posterior antiglide plate. Of the 71 cases studied, 2
      developed peroneal tendonitis. No other type of complication related specifically
      to the antiglide plate was noted. Because of the very low incidence of
      complications and good biomechanical strength, the authors recommend the
      antiglide plate for the fixation of type-B fibular fracture.

PMID- 8130787
TI  - Patient expectations of elective foot surgery.
AB  - A two-part questionnaire was dispensed by five different podiatrists to 73
      surgical patients over a 3-month period. Seventy-two (99%) of the patients were
      satisfied with postoperative results. The average time required to return to
      shoes, work, and exercise was 6.0, 4.5, and 9.0 weeks, respectively. Age, number
      of procedures, and type of procedure did have an effect on these values.
      Subjective comments indicate that surgical patients are most concerned with pain,
      postoperative swelling, and time needed for recovery.

PMID- 8130788
TI  - Keratoacanthoma or verrucous carcinoma? A case report.
AB  - A 75-year-old woman presented with a slow growing lesion on the plantar surface
      of her right foot, which had changed in appearance over several months. The
      patient underwent excision of the suspicious lesion, and a provisional diagnosis
      of keratoacanthoma was given. However, approximately three months later, the
      lesion grew to its original size. Subsequent re-evaluation and consultation
      resulted in changing of the diagnosis to verrucous squamous cell carcinoma. The
      patient underwent a wider excision with split thickness skin grafting. The
      authors discuss this rare pedal entity and the inherent difficulty in both its
      clinical and microscopic differentiation.

PMID- 8130789
TI  - Tc-99m-HMPAO leukocyte scintigraphy for the diagnosis of osteomyelitis in
      diabetic foot infections.
AB  - The diagnosis of osteomyelitis in the presence of soft tissue infection and
      neuropathic bone changes is often difficult in the diabetic foot. Previous
      attempts at scintigraphic diagnosis included Tc-99m methylene diphosphonate,
      Gallium-67 citrate and Indium-111 autologous leukocytes (WBCs). A new agent
      recently available, Technetium-99m-HMPAO labeled white blood cells, shows promise
      as a scintigraphic agent superior to other agents for this purpose. The authors
      discuss this agent and present a case report as a preliminary study.

PMID- 8130790
TI  - Endoscopic plantar fasciotomy versus traditional heel spur surgery: a prospective
      study.
AB  - A comparative study of endoscopic plantar fasciotomy versus traditional type heel
      spur surgery has been performed involving 76 patients and 92 procedures. Sixty
      six of those procedures consisted of endoscopic fasciotomy, whereas 26 involved
      traditional type surgery. Those patients in which the endoscopic fasciotomy was
      performed had significantly less postoperative pain, returned to regular
      activities 4 weeks earlier, and had fewer complications postoperatively than
      those patients involving traditional heel spur surgery. An overview of the
      surgical technique involving endoscopic fasciotomies is presented, as well as
      factors influencing the postoperative outcome, such as duration of preoperative
      symptoms, extent of conservative care, and obesity.

PMID- 8130791
TI  - The treatment of monostotic fibrous dysplasia of the first metatarsal with free
      vascularized fibular bone graft.
AB  - Historically, patients suffering from fibrous dysplasia of the metatarsals faced
      amputation or resection as the treatments of choice. Although the lesion itself
      is not malignant, pain, swelling, and disability dictated the treatment. With
      recent refinements in microvascular surgery, vascularized bone grafting has
      offered a viable alternative for this and similar conditions that offers the
      potential for a functional, pain-free foot.

PMID- 8130792
TI  - Critical analysis of tendo Achillis repair using Achilles tendon rupture
      classification system and repair.
AB  - The author presents a long-term follow-up on Achilles tendon rupture and repair.
      The study includes comparison of Achilles tendon rupture and repair performed by
      the author and other surgeons. There was an alarmingly high incidence of
      complications with the Achilles repair and partial ruptures not reported in the
      literature. Discussion regarding ways to reduce complications using the author's
      classification system, and repair, was effective based on this study.

PMID- 8130793
TI  - Avascular necrosis following distal Chevron osteotomy of the first metatarsal.
AB  - The authors present a retrospective study analyzing the radiographic frequency of
      avascular necrosis following distal Chevron osteotomy of the first metatarsal. A
      total of 164 procedures performed on 104 patients were evaluated radiographically
      at a follow-up period of 12 to 91 months, with a mean followup of 30.4 months.
      Standard anteroposterior radiographs of the foot were taken and evaluated
      independently by each of the three senior authors and two radiologists. No
      radiographs revealed evidence of avascular necrosis in the first metatarsal head.
      While avascular necrosis of the first metatarsal head has been reported to occur
      with varying frequencies, based on this study the authors believe that avascular
      necrosis of the first metatarsal head is an infrequent complication following
      distal Chevron osteotomy.

PMID- 8130794
TI  - A (1-->3,1-->4)-beta-glucan-specific monoclonal antibody and its use in the
      quantitation and immunocytochemical location of (1-->3,1-->4)-beta-glucans.
AB  - Monoclonal antibodies were raised against a (1-->3,1-->4)-beta-glucan-bovine
      serum albumin (BSA) conjugate. One antibody (BG1) selected for further
      characterization, was specific for (1-->3,1-->4)-beta-glucan, displaying no
      binding activity against a (1-->3)-beta-glucan-BSA conjugate and minimal binding
      against a cellopentaose-BSA conjugate. A range of oligosaccharides was prepared
      by enzymatic digestion of (1-->3,1-->4)-beta-glucan, purified by size exclusion
      chromatography and characterized by 1H-NMR and anion exchange chromatography.
      These (1-->3,1-->4)-beta-oligoglucosides, together with (1-->3)-beta- and (1-->4)
      beta-oligoglucosides were used to characterize the binding site of the monoclonal
      antibody (BG1) by competitive inhibition. The monoclonal antibody showed maximal
      binding to a heptasaccharide with the structure Glc(1-->3) Glc(1-->4) Glc(1-->4)
      Glc(1-->3) Glc(1-->4) Glc(1-->4) Glc and was determined to have an affinity
      constant of 3.8 x 10(4) M-1 for this oligoglucoside. The monoclonal antibody
      (BG1) has been used to develop a sensitive sandwich ELISA for the specific
      quantitation of (1-->3,1-->4)-beta-glucans. The assay operates in the range 1-10
      ng ml-1 and shows no significant cross-reaction with tamarind xyloglucan, wheat
      endosperm arabinoxylan or carboxymethylpachyman ((1-->3)-beta-glucan). When used
      with a second-stage, rabbit anti-mouse gold conjugate and viewed under the
      electron microscope, the monoclonal antibody probe was found to bind strongly to
      the walls of the aleurone in thin sections of immature wheat (Triticum aestivum)
      cv. Millewa grains but not to the middle lamella region.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8130795
TI  - Characterization of two cDNAs that encode MAP kinase homologues in Arabidopsis
      thaliana and analysis of the possible role of auxin in activating such kinase
      activities in cultured cells.
AB  - Two cDNA clones, cATMPK1 and cATMPK2, encoding MAP kinases (mitogen-activated
      protein kinases) have been cloned from Arabidopsis thaliana and their nucleotide
      sequences have been determined. Putative proteins encoded by ATMPK1 and ATMPK2
      genes, designated ATMPK1 and ATMPK2, contain 370 and 376 amino acid residues,
      respectively, and are 88.7% identical at the amino acid sequence level. ATMPK1
      and ATMPK2 exhibit significant similarity to rat ERK2 (49%) and Xenopus MAP
      kinase (50%). The amino acid residues corresponding to the sites of
      phosphorylation (Thr-Glu-Tyr) that are involved in the activation of MAP kinases
      are conserved in ATMPK1 and ATMPK2. Northern blot analysis indicates that the
      ATMPK1 and ATMPK2 mRNAs are significantly present in all the organs except seeds.
      Genomic Southern blot analysis suggests that there are a few additional genes
      that are related to ATMPK1 and ATMPK2 in the Arabidopsis genome. Purified Xenopus
      MAP kinase kinase (MAPK kinase) phosphorylates ATMPK1 and ATMPK2 proteins that
      have been expressed in Escherichia coli, activating these enzymes. A rapid and
      transient activation of 46-kDa protein kinase activity that phosphorylated myelin
      basic protein (MBP) was detected when auxin-starved tobacco BY-2 cells were
      treated with synthetic auxin, 2,4-dichlorophenoxyacetic acid (2,4-D). Protein
      kinase activities which phosphorylated the recombinant ATMPK2 protein also
      increased rapidly after auxin treatment in the auxin-starved BY-2 cells. These
      results suggest that auxin may function as an activator of plant MAP kinase
      homologues, as do various mitogens in animal systems.

PMID- 8130796
TI  - Complex spatial and temporal expression of lipoxygenase genes during Phaseolus
      vulgaris (L.) development.
AB  - A new member (Lox1) of the lipoxygenase (LOX) gene family in French bean was
      isolated and its specific expression compared to the general expression pattern
      of related LOX genes. LOX transcripts detected by a French bean cDNA LOX probe
      were generally abundant in young, developing tissues, and LOX protein, detected
      on immunoblots showed a similar distribution. Tissue prints showed that cell
      specific, locally high amounts of LOX protein were observed in some tissues, for
      example in parts of the starch sheath in the hypocotyl and a cell layer in the
      pericarp. The Lox1 gene from Phaseolus vulgaris was shown in genomic Southerns to
      be present as a single copy per haploid genome. RNase protection studies showed
      that the gene is active and the transcription start site was mapped by cDNA
      primer extension. RNase protection studies showed that Lox1 mRNA was present only
      in flowers and embryonic primary leaves, in stems and most strongly, in young
      secondary leaves but not in any of the other organs tested (i.e. not in roots,
      nodules, hypocotyls, cotyledons, older secondary leaves, pericarp or seeds). Lox1
      gene transcripts did not accumulate in leaves in response to methyl jasmonate or
      pathogen inoculation, even though these treatments caused the accumulation of
      other LOX transcripts. Thus, the various lipoxygenase genes are regulated
      differentially during French bean development and in response to different stress
      stimuli, and possible functions are discussed in view of the specific expression
      patterns observed.

PMID- 8130797
TI  - Mutation analysis of the C-terminal vacuolar targeting peptide of tobacco
      chitinase: low specificity of the sorting system, and gradual transition between
      intracellular retention and secretion into the extracellular space.
AB  - The C-terminal propeptide of tobacco (Nicotiana tabacum) chitinase A has been
      shown to be necessary and sufficient for targeting of chitinases to the plant
      vacuole. The sequence specificity of this vacuolar targeting peptide (VTP) has
      now been analysed using transient expression of chitinases in Nicotiana
      plumbaginifolia protoplasts. An extracellular cucumber chitinase, previously used
      as a secreted reporter protein in transgenic tobacco, was also secreted into the
      incubation medium by the transiently transformed protoplasts. Addition of six to
      seven amino acids at the C-terminus to generate the VTP of tobacco chitinase A
      were sufficient to cause retention of most of the cucumber chitinase within the
      protoplasts. The chitinase A itself, as well as a mutant lacking the N-terminal
      chitin-binding domain, were retained to 80% in the protoplasts when low
      concentrations of the plasmid were used in the transient expression system. At
      high concentrations of plasmid, causing high levels of transiently expressed
      chitinase, retention was reduced, indicating saturation of the sorting system.
      Deletion of the C-terminal methionine did not affect the intracellular location,
      but deletion of even a single internal amino acid of the VTP caused predominantly
      secretion of tobacco chitinase A. In contrast, exchanges of amino acids in the
      VTP as well as substitution of the VTP with random sequences had intermediary
      effects that covered the whole range from retention to secretion. The results
      suggest that the sorting system responsible for the diversion of secretory
      proteins to the vacuole has a low specificity for the sequence of C-terminal
      targeting peptides, and that sequence changes in the VTP allow a gradual
      transition from vacuolar retention to secretion.

PMID- 8130798
TI  - K+ channels of stomatal guard cells: bimodal control of the K+ inward-rectifier
      evoked by auxin.
AB  - The influence of the auxins indole-3-acetic acid (IAA) and 1-napthylene acetic
      acid (NAA) on K+ channels and their control was examined in stomatal guard cells
      of Vicia faba L. intact guard cells were impaled with multibarrelled
      microelectrodes to record membrane potentials and to monitor K+ channel currents
      under voltage clamp during exposures to 0.1-100 microM IAA and NAA. Following
      impalements, challenge with either IAA or NAA in the presence of 10 mM KCl
      resulted in the concerted modulation of at least four different currents with
      distinct kinetic characteristics and concentration dependencies. Equivalent
      concentrations of benzoic acid were wholly without effect. Most striking, current
      carried by inward-rectifying K+ channels (IK,in) exhibited a bimodal response to
      both IAA and NAA which was reversed on washing the auxins from the bathing
      medium. The steady-state current was augmented 1.3- to 2-fold at concentrations
      between 0.1 and 10 microM and antagonized at concentrations near 30 microM and
      above. Auxin agonism of IK,in was time- and voltage-independent. By contrast,
      IK,in inactivation at the higher auxin concentrations was marked by a voltage
      dependence and slowing of the kinetics for current activation. Inactivation of
      IK,in by the auxins was relieved when cytoplasmic pH (pHi) was clamped near 7.0
      in the presence of 30 mM Na(+)-butyrate. In addition to the control of IK,in,
      current carried by a second class of (outward-rectifying) K+ channels rose in a
      monotonic and largely voltage-independent manner with auxin concentrations about
      10 microM and above, and IAA and NAA also activated an inward-going current with
      a voltage dependence characteristic of guard cell anion channels. Further changes
      in background current were consistent with a limited activation of the H(+)
      ATPase. Over the concentration range examined, the auxins evoked membrane
      hyperpolarizations and depolarizations of up to +/- 12-19 mV, depending on the
      free-running membrane potential prevailing before auxin additions. Prolonging
      exposures to 100 microM auxin beyond 3-5 min frequently elicited rapid
      transitions to voltages near EK as well as regenerative action potentials.
      However, in every case the voltage response was a predictable consequence of
      auxin action on the K+ channels and, at 100 microM auxin, on the anion
      current.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8130799
TI  - Cloning and structural analysis of the anthocyanin pigmentation locus Rt of
      Petunia hybrida: characterization of insertion sequences in two mutant alleles.
AB  - Anthocyanin biosynthesis in flowers of Petunia hybrida is controlled by the
      regulatory genes an1, an2 and an11. Seven classes of cDNA clones homologous to
      transcripts that are down-regulated in an1-, an2- and an11- mutants were isolated
      via differential cDNA cloning. Genetic mapping, antisense RNA experiments and
      analyses of mutant alleles demonstrated that one class of clones originated from
      the Rt locus. The rt gene has no introns and encodes a protein with homology to
      mammalian glucuronosyl transferases and flavonoid 3-O-glucosyltransferase (UF3GT)
      encoded by the bz1 gene from Zea mays. As the Rt locus controls the
      rhamnosylation of reddish anthocyanin-3-O-glucosides which is the first in a
      series of modifications that finally yield magenta or blue/purple coloured
      anthocyanins, this suggests that rt encodes an anthocyanin rhamnosyl transferase.
      Molecular analysis of two mutant rt alleles showed that their expression is
      blocked by different DNA insertion elements. Mutability of the rt-vu15 allele
      results from the presence of a 284 bp transposable element (dTph1) in the rt
      promoter region, causing a block in transcription. The protein coding region of
      the rt-r27 allele contains a 442 bp insertion (dTph3) resulting in premature
      polyadenylation of rt transcripts. Although dTph3 cannot transpose, it has
      sequence characteristics of transposable elements, suggesting that it is a
      defective member of a new family of transposable elements.

PMID- 8130800
TI  - Isolation and characterization of a cDNA clone corresponding to the Rt locus of
      Petunia hybrida.
AB  - We have isolated, via differential screening of a Petunia hybrida petal cDNA
      library, a cDNA clone that corresponds to the Rt locus which controls the
      conversion of anthocyanidin-3-glucosides to anthocyanidin-3-rutinosides by the
      UDP rhamnose: anthocyanidin-3-glucoside rhamnosyltransferase (3RT). The cDNA
      encodes a 469 amino acid long polypeptide with regions of similarity to the UDP
      glucose: flavonoid glucosyltransferases (3GT) from barley and maize. Some
      sequence similarity was also observed with non-plant glycosyltransferases. Two
      aberrant transcripts are present in most of the rt/rt petunia lines examined.
      Excision of a transposon from an unstable Rt locus of one petunia line (Tr38) is
      associated with a change in transcript size back to wild-type. The Rt transcript
      is most abundant in petals from flowers at an early stage of development and
      levels decline as the flower matures. Transcripts are also detected in the style
      and anthers but not in leaf, stem, root, petiole, ovary or sepals. Incubation of
      leaves in glucose under high light conditions induces the expression of the Rt
      gene as well as other flavonoid pathway genes. In situ hybridization revealed
      that the Rt transcript predominantly accumulates in the epidermal cells of the
      petal, the site of anthocyanin accumulation.

PMID- 8130801
TI  - [Complications of prostatic biopsy. An analysis of a series of 4764 biopsies].

PMID- 8130802
TI  - [Research analysis of local immune response after intravesicular treatment with
      BCG: a review].
AB  - Initial reports focused on purified protein derivative skin test reactivity and
      granuloma formation in patients treated with intravesical bacillus Calmette
      Guerin. Then some investigators using immunohistochemical methods showed that
      some lymphocyte phenotypes where predominant in such infiltrates and that HLA DR
      antigens where strongly expressed following BCG therapy. Similar results where
      obtained in urine using flow cytometric analysis. Additionally some cytokines
      where found at significant levels in urine after BCG instillations. In this paper
      we reviewed these studies, we discussed the meaning of these results and the
      potential value for treatment monitoring.

PMID- 8130803
TI  - [Stenosis of the male urethra: single-stage canal reconstruction using a mobile,
      vascular, pedicled skin graft. 245 personal cases].
AB  - A series of 269 patients treated for male urethral stenoses by the same operator
      using the same management technique from september 1984 to november 1992,
      inspired the author to describe an original one-stage canal reconstructive
      technique, using a mobile, nourished pedicled skin graft. The particularity of
      the technique resides on the large versatility of the pedicle, well vascularised,
      carved out from the subcutaneous cell tissue and the dartos. The scrotal or
      penile skin flap remains attached to the mobile pedicle, giving a much wider
      facility for use, both for penile urethra or perineal urethra repair. The
      technique allows a choice of two methods of plasty repair: the widening patch
      which aims at widening the urethral canal, and the tubularized graft, which aims
      at replacing part or an entire segment of the urethra. Analysis is made on 245
      urethroplasties done for the cure of difficult urethral strictures which made up
      80% of the total number of cases observed (fistulated in 56 cases, multi-operated
      in 47 cases), affecting the penile urethra for 47 cases, the pelvian urethra for
      159 cases, and the membraneous bulb for 39 cases, associated lesions where found
      in 15.9% of the patients. 187 patients where treated by the widening patch
      process whereas 58 underwent neourethral reconstruction by the tubularized graft
      process. Post operative follow-up for over half of the total number of cases was
      4 years. While 224 of the cases treated obtained good results (91.4%), for 15
      patients, the results were considered intermediary (6.1%). Immediate cure was
      obtained for 87.2% of the cases. Lastly, 5 patients presented bad results (2.3%).
      Discussion and analysis are made on the execution of the technique as well as the
      post operative complications encountered: infection (8.9%), urine leakage (6.9
      0), urethrocele (2%). Experience acquired from the use of this management
      technique, showed that it is particularly valuable for the cure of wide,
      recurrent, infected and fistulated stenoses. Its efficiency and reliability
      underline the value of this technique, whose particularity lies on the wide
      manageability of the graft, attached to the pedicle. Its particularity also lies
      on the eclectic choice offered as to the site where the graft is carved off
      (scrotal or penile) and the appropriate plasty to be used (widening patch or
      tubular graft), increasing considerably the favorable chances for surgical
      repair. Finally, the technique's particularity is in its wide indication,
      independently of the characteristics and the cause of the stenoses.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8130804
TI  - [A quiet revolution: the Wallstent urethral prosthesis (Urolume AMS)].
AB  - 14 patients (mean age: 57 years) with posterior urethral stricture were treated
      by internal urethrotomy and implantation of one or several Wallsten prostheses.
      The stent had to be removed in 2 patients (15%), while 12 patients (85%) obtained
      satisfactory urethral patency (mean follow-up: 17.5 months). Complications were
      observed in 50% of cases. They were able to be treated endoscopically with a
      satisfactory result in 5 out of 6 cases (intraprosthetic calculi or stenosis of
      the ends of the stent; 2 patients who became incontinent after insertion of the
      stent regained normal continence after insertion of an artificial sphincter above
      the stent. The Wallsten endoprosthesis therefore appears to be a very
      satisfactory treatment for recurrent complex strictures of the posterior urethra.

PMID- 8130805
TI  - [Sub-urethral diverticulum in women. Apropos of 6 cases].
AB  - Six female patients with a mean age of 40 years presenting with a suburethral
      diverticulum were treated between August 1990 and October 1992. The commonest
      functional symptoms were recurrent urinary tract infections (2/3 of cases) and
      post-voiding urethral discharge (1/2 of cases). Clinical examination revealed a
      tender anterior vaginal mass in only one half of cases. Only retrograde and
      voiding cystourethrography and transvaginal ultrasonography always demonstrated a
      direct or indirect image of the diverticulum. The suburethral diverticulum was
      resected via a transvaginal approach in the ventral supine position after
      sterilisation of the urine by prolonged antibiotic therapy. Urine drainage was
      generally ensured by a suprapubic catheter allowing antegrade cystography on the
      15th day, prior to clamping then removal of the catheter. All but one of the
      patients immediately regained satisfactory micturition without dysuria or stress
      incontinence. Restoration of micturition was delayed in one patient with feelings
      of incomplete bladder emptying, but she urinated normally at three months.
      Postoperative imaging (retrograde and voiding cystourethrography, transvaginal
      ultrasonography) demonstrated resolution of the diverticulum in 5 cases. One
      patient had persistent signs of a small, residual diverticulum on antegrade
      cystography on the 15th day. Suburethral diverticulum is a rare disease of middle
      aged women for which transvaginal surgical excision in the ventral supine
      position gives very good results.

PMID- 8130806
TI  - [Microsurgical treatment of impotence of vascular origin].
AB  - Impotence of vascular origin may be due to a defect of the arterial blood supply,
      a cavernous venous leak or a combination of the two phenomena. Several
      microsurgical techniques have been proposed to restore physiological erectile
      function, without the use of intracavernous injections of vasoactive drugs or
      implantation of penile prostheses. We have used this type of surgery in motivated
      and selected patients for more than 15 years (72 patients treated, 57 patients
      evaluated after surgery). In patients with impotence of arterial origin, we
      perform a Michal II arterio-arterial revascularisation in the case of limited
      proximal or distal lesions with preservation of one of the two dorsal arteries,
      (13 patients) and arterialisation of the deep dorsal vein of the penis in the
      case of diffuse distal lesions (8 patients). 62% of positive results were
      obtained with both forms of revascularisation with a mean follow-up of 22 months.
      In patients with impotence of venous origin (11 patients), we perform
      arterialisation of the deep dorsal vein of the penis, with 92% of positive
      results with a mean follow-up of 12 months. In patients with impotence of
      arterial and venous origin (25 patients), we carry out a Michal II
      revascularisation and ligation of the dorsal vein or arterialisation of the
      dorsal vein achieves 64% and 58% of positive results with a mean follow-up of 12
      months and 5 months, respectively. In the light of these results, the authors try
      to define the place of vascular microsurgery in the treatment of impotence.

PMID- 8130807
TI  - [The inflatable penile prosthesis. Experiences apropos of 58 implants].
AB  - Prosthetic surgery for impotence has been transformed by the development of
      inflatable prostheses in the place of older semirigid models. Despite the
      popularity of this new technique, it raises certain questions concerning the
      functional results and complications of this surgery, which have only
      occasionally been studied concomitantly in the literature. The sexuality of
      patients has generally been evaluated on the basis of answers to a questionnaire
      sent to the patients. This study reports our experience, compared to the data in
      the literature, based on 58 insertions of inflatable prosthesis between October
      1987 and October 1991. After rigorous patient selection and a mean follow-up of
      30 months, the surgeon evaluated the objective results (mechanical functioning of
      the prosthesis, complications) and subjective results (sexuality) in 51 patients.
      69.4% of patients presented an anomaly of prosthesis function, 10.3% developed an
      infection of the prosthesis, 34.5% required removal of the prosthesis, 59%
      declared that they were satisfied sexually and sexual activity was restored in
      55%. This study therefore appears to contradict the optimistic data reported in
      the literature.

PMID- 8130808
TI  - [Emphysematous pyelonephritis. Apropos of 4 cases].
AB  - The authors report four cases of emphysematous pyelonephritis. All patients (3
      females and 1 male) were diabetic. The clinical symptoms and signs were non
      specific. The diagnosis was suggested in every case on conventional x-rays and
      was confirmed by computed tomography, which provides a detailed assessment of the
      lesions by demonstrating diffusion of gas in or beyond the renal compartment (2
      cases). Urine cultures isolated an E. coli in one case and Klebsiella pneumoniae
      in 2 cases. In the fourth patient, Candida albicans was present in the urine at
      pathological levels, as confirmed by the presence of spores on histological
      examination of the nephrectomy specimen. The only effective treatment remains
      nephrectomy which was performed primarily in 2 cases or secondarily, after
      drainage, in the other 2 cases. The prognosis remains severe, with a high
      mortality; 2 of our patients died in a context of severe septic shock with end
      stage renal failure.

PMID- 8130809
TI  - [A silica urinary calculus secondary to the absorption of gelopectose in a
      child].
AB  - The authors report a case of silica-containing urinary stones in a child. This
      drug-induced urinary stone was secondary to absorption of Gelopectose and its
      composition was confirmed by infrared spectrophotometry. Other cases have been
      diagnosed but have not yet been published. Patients with such urinary stones
      should be investigated for possible hypercalciuria or a disorder of H+ metabolism
      in the context of distal tubular acidosis, which may be incomplete and/or
      transient.

PMID- 8130810
TI  - Commingling analysis of adiposity in an Indian population.
AB  - The distributions of five adiposity phenotypes were assessed for the presence of
      commingling in a sample of 756 adults (> or = 30 years old), residing in the
      Chittoor district of Andhra Pradesh, India. Three measures of generalized fatness
      (body mass index, the sum of six skinfolds and the sum of three trunk skinfolds)
      and two indicators of fat patterning (the ratio of trunk to extremity
      subcutaneous fat and the ratio of the subscapular skinfold to the sum of the
      subscapular and the supra-iliac skinfolds) were analysed. Each phenotype was
      adjusted for the effects of (i) age within sex, and (ii) age, energy intake and
      energy expenditure within sex. The distribution of each phenotype, under both
      adjustment schemes, was assessed for evidence of commingling. The commingling
      analyses were performed separately for males (n = 397) and females (n = 359), and
      evidence for heterogeneity in the distribution of each phenotype, by sex, was
      evaluated. There is evidence of commingling in the distribution of each
      phenotype, under both adjustment schemes. Conclusions regarding the distributions
      of these phenotypes are, however, influenced by the specific adjustments made to
      the data. In general, the measures of generalized fatness are more sensitive than
      measures of fat patterning to the specific adjustments applied to the data.
      Interestingly, and in contrast with the majority of commingling analyses of
      adiposity, the smallest components of the commingled distributions often have the
      lowest mean phenotypic value.

PMID- 8130811
TI  - Same growth and different energy intake over four years in children suffering
      from chronic non-specific diarrhoea.
AB  - An increase in energy intake often occurs at weaning and this may depend on the
      current practice of offering energy-dense foods ad libitum. In two-year-old lean
      infants suffering from chronic non-specific diarrhoea (CNSD), the offering of
      food was evaluated by caregivers at every meal on the basis of food need
      expressions and non-starchy vegetable acceptance, taking into account the
      maintenance of good temper and normal activity between meals. The purpose was to
      avoid diarrhoea recurrence. This form of regulation was continued in a
      prospective, controlled, randomized investigation to explore: (i) familial pre
      determination of growth and (ii) the existence of an 'unnecessary' fraction of
      energy intake, i.e. a fraction which may habitually be excluded while still
      maintaining the same normal intermeal behaviour, intellectual and physical
      achievements, growth, skinfold thicknesses and blood parameters. Seven-day intake
      home diaries and clinical assessments were performed every 6 to 12 months. Growth
      records were investigated in siblings. Eighty-two of 91 experimental subjects and
      32 of 41 randomized ones in the control group were followed for up to four years.
      The control group maintained a significantly higher (15-30%) energy intake than
      the experimental children, without any fattening or growth acceleration, or any
      improved results in inter-meal behaviour, intellectual and physical achievements
      or blood parameters for four years. The normal median weight was reached in the
      experimental and control children in the sixth year of life and in the siblings
      in the fourth year of life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130812
TI  - Obesity decreases hepatic glutathione concentrations and markedly potentiates
      allyl alcohol-induced periportal necrosis in the overfed rat.
AB  - Liver biopsies from 9 out of every 10 obese individuals exhibit pathological
      changes of unknown aetiology and 3 out of every 10 reflect severe injury in the
      form of periportal fibrosis. To examine the hypothesis that excessive fibrosis in
      obesity arises in part from a predisposition to injury of the liver by drugs and
      xenobiotics, we administered 5, 10 and 25 mg/kg doses of the model periportal
      hepatotoxin, allyl alcohol, to obese Sprague-Dawley rats and age-matched non
      obese controls. Alanine aminotransferase activity (ALT) in plasma was ten-fold
      more elevated in obese animals than in non-obese animals given the 25 mg/kg dose
      (P < 0.05). On fitting the ALT results to a non-linear, parametric model by
      iterative non-linear least squares regression, we found that the slope of the log
      dose ALT curve was similar for obese and non-obese rats. However, the minimum
      dose required to produce elevated ALT (DMIN) was 50% lower for obese animals
      (DMIN 6.47 +/- 2.75 vs. 13.3 +/- 0.96 mg allyl alcohol; P < 0.05). In a
      subsequent experiment, allyl alcohol was administered to obese rats based on
      ideal body weight, which is defined as the mean total body weight of an age
      matched non-obese animal. With this dosing normalization, the 25 mg/kg ideal body
      weight doses translated to administration of a fixed dose of 13.5 mg allyl
      alcohol to obese rats. Obese rats treated in this fashion exhibited more severe
      necrosis in the periportal zone (median necrosis score 2 versus 0-1, P < 0.05)
      and increased mortality over controls (44% versus 0%; P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8130813
TI  - Exercise-training enhances fat-free mass preservation during diet-induced weight
      loss: a meta-analytical finding.
AB  - A meta-analysis was performed to examine how exercise training and gender
      influence the composition of diet-induced weight loss. The groups did not differ
      with respect to either the amount of body weight lost (mean = -10 +/- 1.4 kg) or
      fat mass lost (mean = -8 +/- 1.1 kg). However, exercise training significantly (P
      < 0.05) reduced the amount of body weight lost as fat-free mass compared to
      dietary restriction only (DO) for the same sex. The percentage of weight lost as
      fat-free mass for diet-plus-exercise (DPE) subjects was approximately half (P <
      0.05) of that for DO subjects of the same sex (DO males = 28 +/- 4% of weight
      lost as fat-free mass; DPE males = 13 +/- 6%, DO females = 24 +/- 2%, DPE females
      = 11 +/- 3%). These data provide evidence that exercise training reduces the
      amount of body weight lost as fat-free mass during diet-induced weight loss. In
      addition, sex differences do not seem to exist with respect to the composition of
      diet-induced weight loss.

PMID- 8130814
TI  - Coronary atherosclerosis in relation to body fatness and its distribution.
AB  - In a cross-sectional study of 226 patients (160 men and 66 women) who underwent
      coronary angiography, the relationships between total body fatness and abdominal
      fat distribution, and angiographically assessed coronary artery disease (CAD)
      were examined. Two different scoring systems were used to quantify the degree of
      CAD: an 'extent score' and a 'myocardial score'. The extent score provides an
      estimate of the extent of coronary atherosclerosis and the myocardial score
      provides an assessment of the amount of myocardium threatened by coronary
      lesions. Total body fatness was estimated using the body mass index (BMI) and the
      waist-to-hip circumference ratio (WHR) was used to assess abdominal fat
      distribution. The weight and height were obtained by questionnaire at the time of
      angiography, and self-reported waist and hip circumference measurements were used
      to calculate WHR. The BMI and WHR were associated with several coronary heart
      disease (CHD) risk factors. However, BMI was not significantly associated with
      either of the CAD scores. The WHR was positively associated with both the extent
      score (rs = 0.18; P < 0.05) and the myocardial score (rs = 0.17; P < 0.05) for
      men and women together, and positively associated with the myocardial score for
      women aged 40 to 70 years (rs = 0.32; P < 0.05). The associations between WHR and
      the CAD scores were not significant after adjusting for several risk factors for
      CHD. These results indicate that other risk factors for CHD may be involved in
      the associations between WHR and CAD.

PMID- 8130815
TI  - Relationships between metabolic clearance rate of insulin and body mass index in
      a female population ranging from anorexia nervosa to severe obesity.
AB  - Changes in the metabolic clearance rate of insulin (MCRI) have been described in
      several pathological conditions. Conflicting data suggest that they may be
      related to either body mass index (BMI) or body composition. This study aimed to
      investigate the relationship between the MCRI and BMI in an exclusively female
      population showing a wide range of BMI. For that purpose, hyperinsulinemic
      normoglycemic glucose clamps were performed in nine anorectic subjects (BMI: 14.5
      +/- 0.8 kg/m2), 11 healthy volunteers (BMI: 20.3 +/- 0.5 kg/m2) and 12 obese
      patients (BMI: 33.0 +/- 0.9 kg/m2). To exclude any influence of the menstrual
      cycle on the MCRI, five healthy women underwent three tests at different days of
      the menstrual cycle: menstruation period, late follicular pre-ovulatory phase and
      luteal phase, in random order. The MCRI, which was quite reproducible in a given
      subject, was not significantly modified by the menstrual cycle. In the
      premenopausal female population studied, the mean (+/- s.e.m.) MCRI normalized
      for body weight (kg) were 35.4 +/- 3.4, 24.7 +/- 1.8 and 14.0 +/- 1.0 ml/kg/min
      (P < 0.01) for anorectic subjects, healthy volunteers and obese patients,
      respectively. These differences were maintained when the MCRI was normalized
      according to corporeal surface (m2) (1018 +/- 75, 859 +/- 67, 638 +/- 40
      ml/m2/min, P < 0.01) or lean body mass (kg) (37.1 +/- 3.4, 32.6 +/- 2.7 and 24.1
      +/- 0.5 ml/kgLBM/min, P < 0.01), but disappeared when MCRI was expressed per kg
      of ideal body weight (24.6 +/- 2.2, 24.6 +/- 2.1 and 22.4 +/- 1.4 ml/kgIBW/min,
      n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130816
TI  - Can the increasing weight of Australians be explained by the decreasing
      prevalence of cigarette smoking?
AB  - In Australia there has been a recent increase in the body mass index (BMI) of the
      population and a decrease in smoking prevalence. Data from the three risk factor
      prevalence surveys conducted by the National Heart Foundation of Australia in
      1980, 1983 and 1989 were analysed to determine if the increase in BMI could be
      explained by the decrease in smoking. For men in all age groups and for women
      aged 50 years or over, there were parallel increases in mean BMI for current
      smokers, ex-smokers and never smokers. For women under 50 years, the pattern of
      increasing BMI over time was less clear. Mean BMI increased over time within each
      five-year age group and in age 'cohorts' and the pattern was independent of
      smoking status. For men and for both groups of women there were similar changes
      in mean BMI over time for most categories of employment status, education and
      physical activity. Thus the increase in body weight cannot be explained by the
      decrease in smoking rate, or by the other factors investigated in this paper.

PMID- 8130817
TI  - The sagittal waist diameter and mortality in men: the Baltimore Longitudinal
      Study on Aging.
AB  - The study objective was to determine the relationship between the abdominal
      sagittal diameter (waist depth) and subsequent mortality. This was a prospective
      study carried out in 981 male participants of the Baltimore Longitudinal Study on
      Aging which is a prospective study at the National Institute on Aging in
      Baltimore. The main outcome measures of the study were total and cause-specific
      mortality occurring during 17,529 person-years. The men were divided by age (cut
      off point 55 years) at the start of follow-up. All-cause and coronary heart
      disease mortality rates (adjusted for age, height and body mass index) increased
      with increasing sagittal diameter in the younger group but not in the older
      group. No significant relationship was observed between the sagittal diameter and
      cancer mortality. Body mass index, skinfolds and waist/hip ratio were not
      significantly related to any of the endpoints studied. The increased risk of
      mortality with increasing sagittal diameter was somewhat stronger when the first
      ten years of follow-up were excluded and was more pronounced at lower levels of
      risk factors such as serum cholesterol, serum triglycerides, plasma glucose and
      diastolic blood pressure and in never plus ex-smokers compared to smokers. The
      study indicates that the abdominal sagittal diameter is a strong predictor of
      mortality in younger adult men independently of age, height, body mass index and
      conventional risk factors for mortality such as smoking, serum lipids and blood
      pressure. Regional adiposity may be a less strong risk factor for mortality in
      older men.

PMID- 8130818
TI  - In vivo regulation of adipose tissue lipoprotein lipase in normal rats made
      hyperinsulinemic and in hyperinsulinemic genetically-obese (fa/fa) rats.
AB  - The objective of this study was to investigate in vivo the effects of various
      durations of hyperinsulinemia on inguinal white adipose tissue lipoprotein lipase
      (LPL). Adult genetically-obese (fa/fa) rats were used as a model of chronic
      hyperinsulinemia. Normal rats infused with insulin as well as with glucose to
      maintain euglycemia for four days were used as a model of short-term
      hyperinsulinemia. Normal rats studied during a euglycemic-hyperinsulinemic clamp
      were used as a model of acute effects of hyperinsulinemia. The levels of LPL
      mRNA, LPL protein and LPL total activity in inguinal white adipose tissue were
      measured. In both chronic and long-term hyperinsulinemia, a marked increase in
      total LPL activity was observed which was associated with an increase in tissue
      LPL protein abundance. After five hours of hyperinsulinemia, as achieved during
      the clamps, only total LPL activity was increased. An increase in LPL mRNA was
      measured only in adipose tissue of obese rats. The differences observed in the
      regulation of LPL mRNA between insulin-treated rats and genetically-obese animals
      may be explained either by the large increase in adipose tissue glucose
      metabolism of insulin-treated rats compared to obese rats and/or by other factors
      that may be present in genetically-obese (fa/fa) rats.

PMID- 8130819
TI  - [Address from the president of the 21st Meetings on Fertility and Eugenics].

PMID- 8130820
TI  - [Present status of Turner's syndrome].

PMID- 8130821
TI  - [Menometrorrhagias of benign origin in the perimenopausal period: explorations
      and current therapeutic approaches].

PMID- 8130822
TI  - [Biochemical examinations of human sperm].

PMID- 8130823
TI  - [Immediate IUD insertion following induced abortion].
AB  - From January 1990 to June 1992, 90 IUD were inserted in immediate post-abortion.
      We studied the tolerance of this contraception with a questionnaire. We got 83
      answers. The rate of complications was 6%. Nine months to three years later the
      continuation rate was 89%. The insertion of an IUD at time of abortion seems to
      be an effective and acceptable solution to the problem of recurrent abortion.

PMID- 8130824
TI  - [IVF in sterility related to ovarian dystrophy].
AB  - Sterility related to ovarian dystrophy is currently treated by means of standard
      inductors of ovulation such as Clomid and HMG. In case of failure, patients are
      recommended in vitro fertilization. In our study of 30 cases of ovarian
      dystrophy, 9 pregnancies occurred after in vitro fertilization. Slow injections
      of purified FSH appear to produce similar results but the method is still under
      evaluation. Our results suggest that after say, two years of failure with
      classical methods in patients with a long history of sterility, in vitro
      fertilization may be expected to give good results.

PMID- 8130825
TI  - [Assisted embryo hatching].
AB  - In spite of the progress in in vitro fertilization (IVF), implantation rate of
      IVF embryos remains low. Many factors seem to be involved in these results. Among
      them, impairment of the hatching process was incriminated by some authors.
      Assisted hatching seems to be an interesting method for repeated failures of IVF.

PMID- 8130826
TI  - [Risky sex and contraception in students in France, Quebec and Spain].
AB  - In the context of a transational study, 404 sexual active 17-21 years-old
      students living in Lyon (France), Montreal (Quebec) and Salamanque and Madrid
      (Spain) have answered a questionnaire dealing with their contraceptive patterns,
      their perceptions of AIDS and their risky sexual behaviors. Results show that
      each group uses a different contraceptive strategy. In France and in Quebec those
      who had their first intercourse before 17 years of age used oral contraceptive
      rather than the condom. As for AIDS girls from Quebec had a higher index of risky
      sexual behaviors (CASH) than French, but the opposite was true among boys, while
      both girls and boys from Spain adopted safer sexual behaviors. Multiple
      regression analysis shows that the CASH rests on different predictors according
      to each national context.

PMID- 8130827
TI  - [Laparoscopic myomectomy. 102 cases].
AB  - Myomectomy was performed by laparoscopy in 102 patients, according to a precise
      technique using the monopolar hook for the uterine incision and intraperitoneal
      sutures. Myomes were mostly removed through the suprapubic puncture site after
      fragmentation or by colpotomy. A laparotomy during the laparoscopic procedures
      was necessary in 2 cases. No complications were observed. A second-look
      laparoscopy or a cesarean section was performed in 24 cases. Post-operative
      adhesions were noted in 3 cases. In our experience, operative laparoscopy has
      several advantages over laparotomy and the risks of complications is low in
      selected cases.

PMID- 8130828
TI  - U.S. health care coverage and costs: historical development and choices for the
      1990s.

PMID- 8130829
TI  - Recent developments in antitrust law and their implications for the Clinton
      health care plan.

PMID- 8130830
TI  - Quality control in health care: developments in the law of medical malpractice.

PMID- 8130831
TI  - Empowerment of advanced practice nurses: regulation reform needed to increase
      access to care.

PMID- 8130832
TI  - Women in clinical trials: are sponsors liable for fetal injury?

PMID- 8130833
TI  - How physicians talk about futility: making words mean too many things.

PMID- 8130834
TI  - Physicians' attitudes toward disclosure of genetic information to third parties.

PMID- 8130835
TI  - Physician attitudes toward the regulation of fetal tissue therapies: empirical
      findings and implications for public policy.

PMID- 8130836
TI  - Moral grounding for the participation of children as organ donors.

PMID- 8130837
TI  - Federal district court frees Haitian refugees.

PMID- 8130838
TI  - Limiting act's protection of physicians defeats aim of patient protection.

PMID- 8130840
TI  - Defendant in civil action may be compelled to undergo HIV test.

PMID- 8130839
TI  - The ailing NHSC scholarship program: government battles recipient in default.

PMID- 8130841
TI  - Cognitive-behavioural treatment for workers with chronic spinal pain: a matched
      and controlled cohort study in Sweden.
AB  - An ambulatory multimodal cognitive-behavioural treatment programme (MMCBT) for
      Swedish workers with chronic spinal pain was formally evaluated. The design was a
      matched cohort study with three repeated measures done in two groups of 35
      referred patients (one exposed to MMCBT and controls exposed to usual care). The
      MMCBT package includes standardised modules of physical treatment, cognitive
      behavioural treatment, education of worker patients, and education of subjects'
      supervisors. The primary outcome variables assessed were absenteeism, disability,
      pain, and depression. Because of a change in Swedish sick leave compensation laws
      affecting records of absence during the study period, absenteeism could not be
      reliably measured among controls. The trend, however, suggested a reduction of
      absenteeism among the subjects in the MMCBT cohort. The findings for disability,
      pain, and depression all showed clinically important and significant beneficial
      changes (ANOVA for repeated measures: disability p = 0.05; pain p = 0.001;
      depression p = 0.01). The direction of the improvements and the size of effect
      were coherent and clinically plausible. The benefits were only among the women in
      the study. These comprised 74% of each group. Further research on larger sample
      sizes and in cohorts more representative of the whole country are needed to
      confirm these encouraging findings and to explore how the benefits might be
      extended to men.

PMID- 8130842
TI  - Assessment of exposure to 2,4-dichlorophenoxyacetic acid in the chemical
      industry: results of a five year biological monitoring study.
AB  - Data on individual exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) in
      herbicide production plants are limited. Hence, the urinary excretion of this
      herbicide was measured during a five year (1985-1989) biological monitoring study
      of 27 men and 18 women employees exposed during the production and formulation of
      2,4-D and related sodium and dimethylamine salts. In separate studies, specimens
      of urine were collected in the morning, or during the last three hours of a
      working shift, or over a 24 hour period (1200 to 1200 or 0800 to 0800) and were
      analysed by an immunochemical method (2,4-D radioimmunoassay (RIA)). Urinary 2,4
      D concentrations varied within a large scale from only a few micrograms/l to
      several 10s of mg/l. During a week, herbicide excretion increased, culminating on
      Friday. At the weekend, when no work was done, 2,4-D elimination decreased but
      did not return to zero in any case. After an interruption of exposure for about
      three weeks, urinary 2,4-D was no longer detectable. About five days after
      restarting work, body concentrations had built up again. Measurements of 2,4-D
      concentrations in air at different work-places showed that herbicide
      concentrations did not exceed 0.5 mg/m3. As well as inhalation, dermal 2,4-D
      absorption seemed to play an important part in total uptake of herbicide.
      Furthermore, a strong correlation was found (r = 0.9628) between 2,4-D urinary
      concentration, adjusted for endogenous creatinine, and the estimated amount of
      absorbed herbicide. Estimated absorbed doses were, in most cases, well below 0.1
      mg 2,4-D/kg body wt/day. Sometimes this concentration was greatly exceeded.
      Thyroid hormone concentrations in blood were measured as well. No notable
      abnormalities were found. Exposed subjects were also typed for histocompatibility
      locus antigens (ABC antigens). The immunochemical determination of 2,4-D in
      specimens of urine proved to be a simple, cost effective, and non-invasive method
      to measure human exposure.

PMID- 8130843
TI  - Extrinsic allergic alveolitis and asthma in a sawmill worker: case report and
      review of the literature.
AB  - A 34 year old sawmill maintenance engineer developed a dry cough that was
      associated with widespread wheezes and crackles in his lungs. His symptoms
      worsened, with work related lethargy, fever, and breathlessness, and the loss of
      a stone in weight. At that time, while still at work, he had a neutrophil
      leucocytosis and increased concentration of gamma globulins. When seen
      subsequently some two months after stopping work, his chest radiograph and lung
      function tests were normal, but the cells recovered at bronchoalveolar lavage
      showed an increase in lymphocytes and mast cells, a pattern consistent with
      extrinsic allergic alveolitis. Serum precipitins were identified to extracts of
      sawdust, wood chips, and bark from the sawmill, and to eight species of mould
      grown from these samples. Specific IgG binding inhibition studies suggested that
      a common epitope present on Trichoderma koningii might be responsible for the
      cross reactivity of the patient's serum with the wood and fungal extracts. A
      diagnosis of wood associated extrinsic allergic alveolitis was made and since
      changing his job the patient has remained well. Wood associated allergic
      alveolitis has not previously been described in British sawmill workers, but has
      been reported in Sweden, with a prevalence of 5%-10% in exposed workers. A review
      of published data suggests extrinsic allergic alveolitis in wood workers is
      primarily caused by inhalation of the spores of contaminating fungi, but inhaled
      wood dust may exert a synergistic effect.

PMID- 8130845
TI  - Prediction of the comparative intensity of pneumoconiotic changes caused by
      chronic inhalation exposure to dusts of different cytotoxicity by means of a
      mathematical model.
AB  - A multicompartmental mathematical model has been used to simulate variations in
      the cytotoxicity of dusts in the kinetics of the retention, in the pulmonary
      region and tracheobronchial lymph nodes, of practically insoluble quartzite and
      titanium dioxide dust particles deposited on the free surfaces of the acini from
      alveolar air. Experiments with these dusts were conducted on rats exposed to
      virtually the same dust concentrations in the air for an experimental period of
      20 weeks and a period of 10 weeks after exposure. Satisfactory approximation to
      the experimental data on the retention of these dusts is obtained by using the
      model parameters that depend either on damage to lung macrophages by phagocytosed
      particles or on the response of the host organism to this damage by enhanced
      recruitment of neutrophilic leucocytes; all the other variables of the model
      being unchanged. The values of the "action integral" computed from this model and
      multiplied by the index of comparative cytotoxicity of particles in vitro
      satisfactorily approximate to quantitative differences in the intensity of
      pneumoconioses caused by the dusts under study by the end of the experimental
      period. On the whole, the results of the mathematical model agree with the
      hypothesis that the cytotoxicity of particles plays a key part in both the
      process of retention of dust in the lung parenchyma and lung associated lymph
      nodes, and the pathological process caused by the retained dust. Thus given the
      factors and conditions on which the deposition of practically insoluble dusts in
      the pulmonary region depends, it is necessary to take into account the
      multiplicative nature of these two effects of cytotoxicity when predicting the
      comparative risk of pneumoconiosis.

PMID- 8130844
TI  - Respiratory symptoms, immunological responses, and aeroallergen concentrations at
      a sawmill.
AB  - After identification of a case of extrinsic allergic alveolitis due to exposure
      to wood dust at a sawmill, all employees at the sawmill where he worked were
      studied with an occupational, environmental, and symptom questionnaire,
      spirometry, skin prick tests, and serum specific IgG measurements. Ninety five of
      current and 14 of 17 ex-sawmill workers were studied. As a basis for comparison,
      a group of 58 workers from a nearby light engineering factory were also studied.
      Few women (6) were employed and they were excluded from the analysis. Workers at
      the sawmill were stratified into high and low exposure groups depending on their
      place of work. This division was supported both by their subjective assessment of
      the dustiness of their environment and the results of personal dust samples.
      There were no significant differences between the three groups in age, height,
      smoking habits, exposure to other causes of extrinsic allergic alveolitis, forced
      expiratory volume in one second, forced vital capacity, atopic state, or
      cutaneous reactivity to moulds. In the high exposure group the prevalence of work
      related cough and nasal and eye symptoms was higher than in the low exposure and
      comparison groups. The prevalence of work related wheeze was similar in both the
      high exposure and comparison groups, but was lower in the low exposure group. The
      prevalences of chronic bronchitis and symptomatic bronchial hyper-reactivity were
      similar in the high and low exposure groups but were lower in the comparison
      group. Serum concentrations of specific IgG against extracts of sawdust and
      Trichoderma koningii were significantly higher in the high exposure group than in
      the other two groups. The prevalence of symptoms suggestive of extrinsic allergic
      alveolitis was 4.4% in the high exposure group, greater than in the low exposure
      group (0%), and the comparison group (1.9%). In conclusion extrinsic allergic
      alveolitis probably occurs in British sawmills, and among the exposed population
      its prevalence may be as high as that reported in Sweden. The allergen
      responsible is likely to be from mould growing on the wood and may be from
      Trichoderma koningii.

PMID- 8130846
TI  - Occupational exposure to water based paint and symptoms from the skin and eyes.
AB  - Water based paints contain organic solvents and many additives, such as biocides,
      surfactants, pigments, binders, amines, and monomers. The chemical complexity may
      introduce new potential health hazards to house painters, in particular
      irritative and allergic disorders. This study was performed to compare how house
      painters experience work with water based paints or solvent based paints, and to
      evaluate whether exposure to water based paints increases mucous membrane and
      dermal symptoms among house painters. 255 male house painters aged 20 to 65 were
      invited to participate in the study. Controls were two industrial populations, in
      total 302 men, without exposure to water based paints. Self administered
      questionnaires were used to assess the painter's experiences of working with
      different types of paints and the occurrence of symptoms in the exposed and
      unexposed groups. Hygiene measurements were performed during normal working days
      when only water based paints and no solvent based paints were used. The painters
      were exposed to low concentrations of dust, metals, ammonia, formaldehyde, and
      volatile organic compounds. The work environment was considered better when
      working with water based paints than with solvent based paints. There were more
      complaints of frequent urination when working with water based paint. Taste or
      olfactory disturbances were less common. General as well as work related eye and
      skin irritation was more common among the exposed workers. For other symptoms no
      significant differences were found. The study indicates that the introduction of
      water based paints has improved the work environment for house painters. Water
      based paints cause less discomfort and airway irritation than the earlier solvent
      based paints. Adverse general health effects seem low. Some of the painters may
      have dermal symptoms caused by the components in water based paints.

PMID- 8130847
TI  - Ethanol induced modification of m-xylene toxicokinetics in humans.
AB  - This study was undertaken to determine whether previous subacute treatment with
      ethanol could modify the kinetics of m-xylene in humans. A group of six
      volunteers was exposed twice to either 100 or 400 ppm of m-xylene during two
      hours (between 0800 and 1000). Ethanol was given orally in the early evening on
      each of two consecutive days before exposures (total ethanol intake of 137 g).
      Such ethanol pretreatment affected the kinetics of m-xylene but only at the high
      exposure (400 ppm). The modifications were: (1) decreased concentration of m
      xylene in blood and alveolar air during and after exposure; (2) increased urinary
      excretion of m-methylhippuric acid at the end of exposure. Ethanol treatment also
      enhanced the elimination of antipyrine in saliva. Overall, this study showed that
      the effect of enzyme induction on the metabolism of m-xylene, after ethanol
      ingestion, depends on the exposure concentration and is not likely to occur as
      long as the exposure concentrations remain under the current maximum allowable
      concentration (100 ppm) in the workplace.

PMID- 8130848
TI  - Age specific interactions between smoking and radon among United States uranium
      miners.
AB  - United States uranium miners who smoked have death rates from lung cancer that
      are intermediate between the rates predicted by the additive and multiplicative
      models (on a ratio scale) across all age groups. Age specific patterns of
      interaction have not been thoroughly examined, and most analyses have been
      internal ones in which there was no truly non-exposed group. Here age specific
      death rates of lung cancer among ever smoking uranium miners have been examined
      for conformity with the additive and multiplicative models. The multiplicative
      model fits well for the youngest and oldest categories, but poorly for the middle
      age ranges. In the middle age range, predicted rates under the multiplicative
      model were quite high, surpassing the corresponding United States death rates for
      all causes combined. If the multiplicative model is assumed to hold across all
      ages, one hypothesis that might explain the observed age specific patterns is
      that the full expression on the multiplicative model might not be seen at certain
      ages due to a limited pool of miners susceptible to lung cancer. These data,
      however, have several limitations such as small numbers of deaths from lung
      cancer among never smokers, the use of qualitative rather than quantitative
      smoking and radon exposure data, and ignorance of the underlying biological
      mechanisms of interaction.

PMID- 8130849
TI  - Lung retention of cerium in humans.
AB  - A retrospective study was conducted to evaluate lung retention of particles
      containing cerium in subjects with and without previous occupational exposure to
      mineral dusts. Analytical transmission electron microscopy was performed on 459
      samples of bronchoalveolar lavage (BAL) fluid and 75 samples of lung tissue.
      Study of the distribution of mineralogical species in human samples showed that
      particles containing cerium were encountered in less than 10% of subjects. The
      proportion of subjects with particles containing cerium in their biological
      samples was not different between controls and subjects with previous
      occupational exposure to fibrous or nonfibrous mineral dusts. This was considered
      as the background level of lung retention of cerium in the general population. By
      contrast, determination of the absolute concentration of particles containing
      cerium in BAL fluid and lung tissue samples showed that 1.2% (from BAL fluid) and
      1.5% (from lung tissue) of subjects with previous exposure to mineral particles
      had high lung retention of particles containing cerium. This study is believed to
      be the first one in which lung retention of cerium was estimated in the general
      population.

PMID- 8130850
TI  - Iron associated with asbestos bodies is responsible for the formation of single
      strand breaks in phi X174 RFI DNA.
AB  - The ability of amosite cored asbestos bodies isolated from human lungs to
      catalyse damage to phi X174 RFI DNA in vitro was measured and compared with that
      of uncoated amosite fibres with a similar distribution of length. Asbestos bodies
      (5000 bodies) suspended for 30 minutes in 50 mM NaCl containing 0.5 micrograms
      phi X174 RFI DNA, pH 7.5, did not catalyse detectable amounts of DNA single
      strand breaks. Addition of the reducing agent ascorbate (1 mM), however, resulted
      in single strand breaks in 10% of the DNA. Asbestos bodies in the presence of a
      low molecular weight chelator (1 mM) and ascorbate catalysed the formation of
      single strand breaks in 21% of the DNA with citrate or 77% with ethylenediamine
      tetra-acetic acid (EDTA), suggesting that mobilisation of iron may increase
      damage to DNA. Preincubation for 24 hours with desferrioxamine B, which binds
      iron (Fe (III)) and renders it redox inactive, completely inhibited the
      reactivity of asbestos bodies with DNA, strongly suggesting that iron was
      responsible. Amosite fibres (5000 fibres/reaction), with a similar length
      distribution to that of the asbestos bodies, did not catalyse detectable amounts
      of single strand breaks in DNA under identical reaction conditions. The results
      of the present study strongly suggest that iron deposits on the amosite core
      asbestos bodies were responsible for the formation of DNA single strand breaks in
      vitro. Mobilisation of iron by chelators seemed to enhance the reactivity of
      asbestos bodies with DNA. It has been postulated that the in vivo deposition of
      the coat material on to fibres may be an attempt by the lung defenses to isolate
      the fibre from the lung surface and thus offer a protective mechanism from
      physical irritation. These results suggest, however, that the iron that is
      deposited on asbestos fibres in vivo may be reactive, potentially increasing the
      damage to biomolecules, such as DNA, above that of the uncoated fibres.

PMID- 8130851
TI  - Retention patterns of asbestos fibres in lung tissue among asbestos cement
      workers.
AB  - Retention patterns in lung tissue (determined by transmission electron microscopy
      and energy dispersive spectrometry) of chrysotile, tremolite, and crocidolite
      fibres were analysed in 69 dead asbestos cement workers and 96 referents. There
      was an accumulation of tremolite with time of employment. Among workers who died
      within three years of the end of exposure, the 13 with high tremolite
      concentrations had a significantly longer duration of exposure than seven in a
      low to intermediate category (medians 32 v 20 years; p = 0.018, one sided).
      Crocidolite showed similar patterns of accumulation. In workers who died more
      than three years after the end of exposure, there were no correlations between
      concentrations of amphibole fibres and time between the end of exposure and
      death. Chrysotile concentrations among workers who died shortly after the end of
      exposure were higher than among the referents (median difference in
      concentrations 13 million fibres (f)/g dry weight; p = 0.033, one sided). No
      quantitative differences in exposure (duration or intensity) could be shown
      between workers with high and low to intermediate concentrations. Interestingly,
      all seven workers who had had a high intensity at the end of exposure (> 2.5
      f/ml), had low to intermediate chrysotile concentrations at death, whereas those
      with low exposure were evenly distributed (31 subjects in both concentration
      categories); hence, there was a dependence between last intensity of exposure and
      chrysotile concentration (p = 0.014). Among 14 workers with a high average
      intensity of exposure, both those (n = 5) with high tissue concentrations of
      chrysotile and those (n = 10) with high tissue concentrations of tremolite fibres
      had more pronounced fibrosis than those with low to intermediate concentrations
      (median fibrosis grades for chrysotile: 2 v 1, p = 0.021; for tremolite: 2 v 0.5,
      p = 0.012). Additionally, workers who died shortly after the end of exposure with
      high concentrations of chrysotile and crocidolite had smoked more than those with
      low intermediate concentrations (medians for chrysotile 35 v 15 pack-years, p =
      0.030; for crocidolite 37 v 15 pack-years, p = 0.012). The present data indicate
      that chrysotile has a relatively rapid turnover in human lungs, whereas the
      amphiboles, tremolite and crocidolite, have a slower turnover. Further,
      chrysotile retention may be dependent on dose rate. Chrysotile and crocidolite
      deposition and retention may be increased by tobacco smoking; chrysotile and
      tremolite by fibrosis.

PMID- 8130852
TI  - Four cases of mesothelioma among Finnish anthophyllite miners.
AB  - Four cases of mesothelioma in a cohort of 999 Finnish anthophyllite miners and
      millers are described. Three deaths were due to pleural mesothelioma and one to
      peritoneal mesothelioma among the total of 503 male deaths up to 1991. All four
      patients with mesothelioma had had long term (13 to 31 years) exposure in
      anthophyllite mining and milling. The latency time from the onset of employment
      until diagnosis was 39 to 58 years. All four patients were smokers or ex-smokers
      and had asbestosis. In three of the cases the pulmonary fibre concentration and
      fibre type were analysed by transmission electron microscopy. High concentrations
      (270 to 1100 million fibres/g dry tissue) of anthophyllite fibres were detected.
      The anthophyllite fibres were thicker and had lower aspect ratios than the values
      reported for crocidolite fibres retained in the lungs of patients with
      mesothelioma.

PMID- 8130853
TI  - General pediatrics in a time of change. Inventing the future.

PMID- 8130854
TI  - The role of socioeconomic status and injury morbidity risk in adolescents.
AB  - OBJECTIVE: To examine the patterns of socioeconomic status and injury morbidity
      in adolescents. DESIGN: Prospective cohort study. SETTING: Metropolitan school
      district in Allegheny County, Pennsylvania. PARTICIPANTS: There were 1245
      students (89%) recruited from 1400 aged 12 to 16 years. INTERVENTIONS: None.
      MEASURES AND RESULTS: Baseline variables of socioeconomic status used for this
      analysis included township of residence (from the 1990 census data ranked by the
      percentage of households below the poverty level) and employment status of the
      parents (student self-report). Life-table analysis revealed no differential risk
      of injury by socioeconomic status. Similar results were found when stratified by
      gender, race, injury type (sport vs nonsport), and injury place (school vs home).
      CONCLUSIONS: The results indicate that in this cohort of adolescents,
      socioeconomic status does not seem to be a contributing risk factor for injury.

PMID- 8130855
TI  - Human immunodeficiency virus infection in infants during the first 2 months of
      life. Reliable detection and evidence of in utero transmission.
AB  - OBJECTIVE: To evaluate the clinical utility of a polymerase chain reaction (PCR)
      method for detecting human immunodeficiency virus (HIV) infection in infants 2
      months of age or younger who were born to HIV-positive mothers. DESIGN:
      Prospective, longitudinal study lasting 3 years. The PCR tests were performed
      with coded peripheral blood mononuclear cell lysates, and results were compared
      with findings using Centers for Disease Control and Prevention (CDC) (Atlanta,
      Ga) criteria defining HIV infection in children. SETTING: Hospitals, particularly
      a pediatric hospital in Washington, DC. PATIENTS: Newborns, young infants, and
      HIV-infected mothers. OUTCOME MEASURE: Presence or absence of pediatric HIV
      infection using CDC criteria compared with a diagnosis based on the detected
      presence or absence of HIV proviral DNA using PCR testing. RESULTS: One or more
      blood samples obtained by 62 days of age from 30 (94%) of 32 HIV-infected infants
      were positive for HIV by routine PCR testing. Blood samples from 32 infants now
      confirmed to be uninfected tested negative for HIV. Human immunodeficiency virus
      DNA was detected in blood samples obtained within 48 hours of birth from eight of
      nine infected infants. In six of these newborns as well as most older infants,
      HIV DNA was present in such quantity that it was detectable in specimens
      equivalent to 0.01 mL or less of the original blood sample. CONCLUSIONS: Our PCR
      procedure can reliably detect the presence or absence of HIV infection during the
      first 2 months of life. The frequent presence and not uncommon high titer of HIV
      DNA within 48 hours of birth suggest that much of the transmission of HIV from
      mother to infant occurs well before birth.

PMID- 8130856
TI  - Association between bicycle helmet legislation, bicycle safety education, and use
      of bicycle helmets in children.
AB  - OBJECTIVE: To determine the association between bicycle helmet legislation and
      bicycle safety education and the use of bicycle helmets by children under age 16
      years. DESIGN: Anonymous questionnaire and direct observations of bicycle helmet
      use. SETTING: Four predominantly white, upper-middle class suburbs of Cleveland,
      Ohio. PARTICIPANTS: All students in grades 1 through 7 attending public school on
      the day of the survey and children riding bicycles in a direct observational
      study. INTERVENTIONS: Beachwood had bicycle helmet legislation and safety
      education. Orange had only bicycle helmet legislation. Pepper Pike and Moreland
      Hills did not have bicycle helmet legislation or safety education. RESULTS: In
      Beachwood, 416 (67.6%) of 615 children who owned a bicycle reported always
      wearing their helmets, and 72 (85%) of 85 children directly observed were wearing
      bicycle helmets. In Orange, 103 (37.2%) of 277 children who owned bicycles
      reported always wearing helmets, whereas 41 (17.9%) of 229 children in Moreland
      Hills and 78 (21.5%) of 362 children in Pepper Pike reported always wearing
      helmets. Helmet use was significantly (P < .001) higher in Beachwood, with
      legislation and education, than in the other communities; helmet use was
      significantly (P < .001) higher in Orange, with legislation alone, than in
      Moreland Hills and Pepper Pike, with no programs. CONCLUSIONS: There was a
      dramatic association between reports of increased helmet use and bicycle helmet
      legislation plus education; the association was stronger than that found with
      legislation only.

PMID- 8130857
TI  - Childhood thyroid cancer. Characteristics and long-term outcome in children
      irradiated for benign conditions of the head and neck.
AB  - OBJECTIVE: To determine the characteristics and long-term outcome of radiation
      induced thyroid cancer in children. DESIGN: Retrospective review of a cohort of
      4296 irradiated patients who received childhood radiation treatment to the head
      and neck area at the same hospital. PATIENTS: Forty-one children who were younger
      than 20 years when thyroid cancer developed in them and 77 adults in whom thyroid
      cancer developed. All 118 cases were diagnosed before 1974 and were followed up
      for a median of 19.4 years. RESULTS: Children presented with clinically palpable
      lymph nodes more often than adults (30.7% vs 15.1%, P = .05) and had more
      recurrences (39% vs 16%, P = .05). Despite these frequent recurrences, only one
      patient (an adult) died of thyroid cancer. Seventy percent of the recurrences
      occurred during the first 10 years of follow-up, but recurrences continued after
      20 years. The adults had previously identified factors that predicted the risk of
      recurrences, but none could be identified in the children. CONCLUSION: The
      presentation and relatively good outcome of radiation-induced thyroid cancer in
      children is similar to that in nonirradiated children. Frequent and late
      recurrences call for lifelong follow-up.

PMID- 8130858
TI  - Bromide pharmacokinetics in cystic fibrosis.
AB  - OBJECTIVE: Individuals with cystic fibrosis (CF) have altered kinetics for a
      number of drugs, most often an increased volume of distribution (Vd) per body
      weight and increased clearance per body weight. To further evaluate those
      differences, we studied bromide kinetics (Vd, elimination rate constant, and
      clearance) and body mass index in eight adults with mild-to-moderate forms of CF,
      21 obligate carriers of the CF gene, and 21 healthy controls. Bromide
      distribution approximates the extracellular fluid volume and bromide is excreted
      unchanged by the kidney. DESIGN: Individuals were given a single oral dose of
      bromide (50 mg/kg), and serum bromide concentrations were measured over 4 weeks.
      Bromide pharmacokinetics (Vd, elimination rate constant, and clearance) were
      determined using a one-compartment model with first-order kinetics. Body mass
      index was determined for each individual. RESULTS: Individuals with CF had a
      significantly greater lean body mass per kilogram as estimated by body mass index
      compared with individuals in the obligate carrier and control groups. The mean
      (+/- SD) Vd per kilogram for the CF group (311 +/- 29 mL/kg) was significantly
      greater than that of the obligate carrier group (261 +/- 26 mL/kg) and the
      control group (274 +/- 30 mL/kg). However, the mean (+/- SD) Vd per square meter
      for the three groups was similar. The mean elimination rate constant for the CF
      group (3.55 +/- 0.98 x 10(-3)/h) was significantly greater compared with the mean
      elimination rate constant for the obligate carrier group (2.55 +/- 0.36 x 10(
      3)/h) and the control group (2.58 +/- 0.49 x 10(-3)/h). The mean (+/- SD)
      clearance per kilogram was also significantly greater for the CF group (1095 +/-
      283 microL/kg per hour) compared with the obligate carrier group (664 +/- 100
      microL/kg per hour) and the control group (700 +/- 115 microL/kg per hour).
      CONCLUSIONS: These findings indicate that individuals with CF have a greater Vd
      per kilogram for bromide and drugs that distribute in the extracellular fluid
      volume because of their greater lean body mass per kilogram. The findings also
      suggest that individuals with CF have a greater renal clearance of bromide and
      presumably of other anionic drugs excreted by the kidney. The results emphasize
      the importance of body composition in drug disposition.

PMID- 8130860
TI  - Radiological case of the month. Case 1. Anterior nasal stenosis as a cause of
      neonatal nasal airway obstruction.

PMID- 8130859
TI  - Performance of screening tools for mental health problems in chronically ill
      children.
AB  - We examined the sensitivity, specificity, positive predictive value, and negative
      predictive value of three different screens for child and adolescent emotional
      and behavioral disorders among a large group of chronically medically ill
      children and adolescents. The performance of the Child Depression Inventory
      (CDI), Pediatric Symptom Checklist (PSC), and Child Behavior Checklist (CBCL) in
      detecting emotional or behavioral disorders was compared with the diagnoses
      obtained by an intensive structured psychiatric interview (Diagnostic Interview
      Schedule for Children, Version 2.1) of 112 children and adolescents with chronic
      medical conditions, and their parents, recruited from a tertiary-care medical
      center. The CDI, PSC, and CBCL all demonstrated low sensitivity, positive
      predictive value, and negative predictive value, but high specificity. We
      conclude that these three commonly used screening tests performed poorly as
      screens because of their low sensitivity among children and adolescents with
      chronic medical conditions. The CDI, PSC, and CBCL should not be relied on as
      screening instruments for psychopathologic conditions in children and adolescents
      with chronic medical conditions. Although the screening measures studied may
      confirm a clinician's concern, the negative findings of this study suggest their
      use may be misleading and undermine the pediatrician's clinical judgment.

PMID- 8130861
TI  - Pathological case of the month. Case 1. Bart's hemoglobin hydrops fetalis
      syndrome.

PMID- 8130862
TI  - Pathological case of the month. Case 2. Rhabdomyosarcoma presenting with
      extensive marrow necrosis.

PMID- 8130863
TI  - Picture of the month. Alagille syndrome (arteriohepatic dysplasia).

PMID- 8130864
TI  - Detection of measles virus from clinical samples using the polymerase chain
      reaction.
AB  - OBJECTIVE: To evaluate the usefulness of the polymerase chain reaction to detect
      the measles virus sequence using clinical samples. DESIGN: Centers for Disease
      Control and Prevention case definition of measles with or without IgM serology as
      a standard. SETTING: A laboratory in the Department of Pediatrics of the Hokkaido
      University Hospital, Sapporo, Japan. PATIENTS: Thirty-two serum samples, 16
      throat swab samples, and nine cerebrospinal fluid samples from 32 patients with
      measles, including four patients with central nervous system involvement, and one
      serum sample and two throat swab samples from two patients with modified courses
      of measles were obtained. Ten serum samples, 10 throat swab samples, and 10
      cerebrospinal fluid samples were obtained from patients without apparent measles
      infection as negative controls. MEASUREMENTS AND MAIN RESULTS: Sensitivity and
      specificity were comparable with those as obtained by culture or other methods
      reported in the literature. The polymerase chain reaction was positive in 24
      (75.0%) of 32 by serum samples and in 13 (81.3%) of 16 by throat swab samples
      from the patients with measles, in contrast to none within the negative control
      group. In three of the four patients with central nervous system involvement, the
      measles virus sequence was detected in cerebrospinal fluid samples obtained
      within 1 day following the onset of the manifestations. All three samples from
      the patients with modified measles yielded positive results. CONCLUSIONS: The
      polymerase chain reaction can be used with sufficient sensitivity and specificity
      to detect the measles virus sequence using clinical samples. Transient and direct
      invasion of the central nervous system by this virus at the initial stage of the
      central nervous system involvement was strongly suggested.

PMID- 8130865
TI  - Maximizing the stability of oxygen delivered via nasal cannula.
AB  - BACKGROUND: The effective fractional inspired oxygen concentration (FiO2) of
      supplemental oxygen provided to infants via nasal cannula may be adjusted by
      changing cannula flow rate or oxygen concentration, factors within our control.
      However, FiO2 also varies with changes in the patient's breathing, factors beyond
      our control. While a stable oxygen delivery is desirable, combinations of flow
      and concentration that maximize stability over time need to be studied.
      OBJECTIVE: To assess the impact of different weaning strategies on the stability
      of inspired oxygen concentrations delivered to infants via nasal cannulas and to
      identify optimum strategies maximizing that stability. DESIGN: Theoretical
      analysis and comparison with previously published measurements. METHODS: We
      derived equations predicting the FiO2 delivered to infants via nasal cannula,
      incorporating traditional adjustments of cannula flow rate and oxygen
      concentration, as well as considering the impact of the infant's inspiratory
      time, tidal volume, and fraction of nasal breathing. We compared predicted
      results with previously published measures and evaluated strategies to maximize
      oxygen delivery stability over time. RESULTS: Predicted values correlated well
      with published hypopharyngeal measurements (r = .97) and were unbiased, accurate
      predictors of FiO2. Effective FiO2 was least likely to be affected by changes in
      patient-controlled controlled factors when the nasal cannula flow rate was as low
      as possible. CONCLUSIONS: To minimize variability in oxygen delivery via nasal
      cannula to infants, cannula flow should be reduced to the lowest possible flow by
      using undiluted (100%) oxygen. Supplemental oxygen may then be weaned by making
      small reductions in cannula flow. Cannula oxygen concentration should be reduced
      below 100% only after the minimum calibrated flow rate is reached. Such a
      strategy may maximize the stability of delivered oxygen over time as well as
      minimize the size of changes in delivered oxygen at each step of the weaning
      process.

PMID- 8130866
TI  - Child safety seat use for infants with Pierre Robin sequence.
AB  - OBJECTIVE: To determine what child restraints would accommodate infants with
      Pierre Robin sequence who often require special attention in motor vehicle travel
      since microagnathia usually requires a prone position to keep the infant's airway
      open. RESEARCH DESIGN: Dynamic testing and clinical trial. SETTING: An Indiana
      children's hospital providing primary and tertiary care. PATIENTS: Four patients
      with Pierre Robin sequence are described to illustrate use of the modified infant
      car seat and the appropriateness of the car bed restraints for meeting
      requirements for prone positioning during travel. SELECTION PROCEDURES:
      Convenience sample. INTERVENTION: Selected restraints were loaned to families
      through a clinical setting until the patient was able to use a conventional child
      restraint. MEASUREMENTS AND RESULTS: Three child restraint systems were
      determined to accommodate the prone position necessary to keep the airway open
      for children with Pierre Robin sequence. Dynamic crash testing demonstrated the
      crashworthiness of an infant car seat modified to allow for prone positioning.
      Through a clinical trial, two car bed restraints were also found to provide safe
      prone positioning of infants. CONCLUSIONS: To enable safe transportation for
      infants with Pierre Robin sequence, health care providers can direct parents to
      appropriate resources for travel and can monitor the airway and oxygenation of
      the infant with Pierre Robin sequence before hospital discharge.

PMID- 8130867
TI  - Methylene blue-induced Heinz body hemolytic anemia.
AB  - OBJECTIVE: To describe the manifestations of methylene blue toxicity, with a
      review of the literature. DESIGN: A descriptive analysis of physical findings and
      significant laboratory tests in patients with methylene blue toxicity. SETTING: A
      pediatric referral center. PATIENTS: Two infants, one a neonate with trisomy 21
      exposed to methylene blue as an intraoperative diagnostic marker and the other a
      neonate treated with methylene blue for type II glutaric acidemia. INTERVENTIONS:
      Laboratory tests to define the occurrence of methylene blue toxicity,
      phototherapy for hyperbilirubinemia, and transfusions for anemia. MEASUREMENTS
      AND RESULTS: Within hours after exposure to methylene blue, the infants voided
      green-blue urine, followed by hyperbilirubinemia, recurrent anemia requiring
      transfusions, and red blood cell dysmorphology, including the appearance of
      blister cells and Heinz bodies visible in both Wright's- and supravital-stained
      peripheral blood smears. After the initiation of phototherapy, both infants
      exhibited cutaneous bullae followed by desquamation. CONCLUSION: Significant
      neonatal morbidity may occur following postpartum administration of methylene
      blue. Toxic manifestations include hyperbilirubinemia, Heinz body hemolytic
      anemia, and possibly desquamation of the skin. In our infants toxicity was
      secondary to an overdose of methylene blue, as is true for most of the previously
      reported cases. Methods for defining the mechanism of dye-related hemolysis and
      simple screening tests for elucidating the unique sensitivity of certain
      individuals to dye toxicity are suggested.

PMID- 8130868
TI  - A case-study approach. Fellows' perceptions of a teaching course.
AB  - OBJECTIVE: To determine general and behavioral pediatric fellows' perceptions of
      a formal teaching course. DESIGN: Qualitative research design using a case-study
      approach. SETTING: Children's Hospital in Boston, Mass. PARTICIPANTS: All first
      year general and behavioral pediatric fellows (n=5) taking the teaching course.
      INTERVENTION: A 12-week teaching course given to all participants.
      MEASUREMENTS/MAIN RESULTS: Data were collected using questionnaires completed by
      fellows; focused, open-ended interviews with fellows; and student ratings of
      fellows' teaching. Analysis revealed that after the course, the fellows perceived
      "teaching'' as an interactive, student-directed process; attained a greater
      awareness of the value of feedback; recognized new teaching opportunities; and
      changed their teaching strategies to reflect student-directed teaching.
      CONCLUSION: This formal course influenced fellows' approach to teaching.

PMID- 8130870
TI  - Heart transplantation. Other ethical questions.

PMID- 8130869
TI  - Equitable distribution in pediatric heart transplantation. Arguments in favor of
      a national list.
AB  - The disparity between the supply and demand for pediatric donor hearts remains
      the major constraint in pediatric heart transplantation. This disparity draws
      attention to the importance of an equitable distribution policy for pediatric
      hearts. An examination of the policy on pediatric heart distribution shows that
      although a governmental task force recommended that these organs be allocated
      according to a national list, the current policy, developed by the United Network
      of Organ Sharing, emphasizes the local distribution of pediatric hearts. The
      decision to allocate organs locally was based on both theoretical and practical
      concerns about national distribution. In analyzing these concerns, we conclude
      not only that a national list may be a more equitable means of distribution but
      also that the arguments against a national list no longer justify a policy
      favoring local distribution. We suggest, therefore, that the time has come to
      reconsider implementation of a national list for pediatric heart distribution.

PMID- 8130871
TI  - Salivary gland radionuclide imaging abnormalities in infants with congenital
      hypothyroidism.

PMID- 8130872
TI  - Exacerbation of chronic idiopathic thrombocytopenic purpura following measles
      mumps-rubella immunization.

PMID- 8130873
TI  - Implantable intravenous access devices in children with hemophilia.

PMID- 8130874
TI  - Cholesterol: myth vs reality?

PMID- 8130875
TI  - Growing neglect of American children.

PMID- 8130876
TI  - The use of primidone in neonates with theophylline-resistant apnea.

PMID- 8130877
TI  - Dissipating the foggy myth of the black cloud.

PMID- 8130878
TI  - Immune thrombocytopenic purpura in infants.

PMID- 8130879
TI  - Chemistry of zirconia and its use in chromatography.
AB  - The purpose of this review is to shed some light on the complex properties of
      zirconia's surface chemistry in order to better understand its behaviour under
      chromatographic conditions. We emphasize the great differences between the much
      better known chemistry of a silica surface and the chemistry of zirconia's
      surface. The review describes both the physical and chemical properties of
      zirconium dioxide from a chromatographic point of view. The chemistry of
      monoclinic zirconia surface is developed from its underlying crystalline
      structure. The paper describes the dependence of the specific surface area, pore
      volume, porosity and mechanical strength on thermal treatment. Methods of
      synthesis of chromatographically useful zirconia are outlined. The review also
      covers the adsorption properties of zirconia at both gas-solid and liquid-solid
      interfaces. Adsorption of water, carbon dioxide, carbon monoxide and ammonia are
      described and the controversies concerning the surface concentration of
      adsorption sites are presented. The complex chemistry of a zirconia surface is
      pointed out and the importance of ligand exchange reactions is emphasized. In
      contrast to a silica surface, ligand exchange plays an important role in liquid
      chromatographic applications of zirconia. Strong, hard Lewis acid sites, present
      on a zirconia surface, can interact with hard Lewis bases and these interactions,
      sometimes troublesome, can be successfully exploited even for protein
      separations. Zirconia's surface can be modified in many ways: dynamically, by
      addition of competing Lewis bases to the mobile phase, or permanently, by
      covering its surface with polymers or by depositing carbon. The review also shows
      that the main difficulty in achieving a wider variety of applications is probably
      our lack of knowledge and poor understanding of zirconia's surface chemistry.

PMID- 8130880
TI  - Ion-exchange-immunoaffinity purification of a recombinant baculovirus Plasmodium
      falciparum apical membrane antigen, PF83/AMA-1.
AB  - A two-step purification regime has been developed for a quantitatively minor,
      putatively transmembrane, M(r) 83,000, apical membrane blood stage vaccine
      candidate antigen of Plasmodium falciparum (PF83/AMA-1), that has been expressed
      as a full-length baculovirus recombinant protein, PF83-7G8-1. The first step
      utilizes a new approach to high-performance ion-exchange chromatography (HPIEC)
      in which elution conditions are not only defined by charge, but also by
      hydrophobicity. HPIEC fractionation involves successive sodium chloride gradient
      anion-exchange elutions (A and B), where a change in the non-ionic detergent
      polyoxyethylenealkylether C10E5 concentration between elutions A and B (from
      0.01% to 0.1% (w/v) respectively), results in a fraction that comprises from 2%
      to 9% PF83-7G8-1. Subsequent column immunoaffinity purification of this fraction
      on Q-Sepharose CL 4B-28G2dc1 mAb yields a PF83-7G8-1 preparation that is 56%
      pure. Rat mAb 28G2dc1 recognizes a C-terminal region that is conserved and cross
      reactive within the AMA-1 family, thus permitting recombinant and native full
      length AMA-1 molecules from other species to be purified for molecular analysis.
      Immunological and molecular characterisation of the vaccine-related
      characteristics of purified PF83/AMA-1 are now underway.

PMID- 8130881
TI  - Synthesis of novel tellurium containing analogues of choline and acetylcholine
      and their quantitation by pyrolysis-gas chromatography-mass spectrometry.
AB  - Methods for the synthesis and quantitation of the novel choline analogues,
      telluronium choline and acetyltelluronium choline, are described. An assay
      procedure utilizing pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS)
      with cold trapping was developed with [2H4]telluronium choline and
      [2H4]acetyltelluronium choline as internal standards. The telluronium compounds
      were ion-pair extracted from tissue with dipicrylamine, washed with 2-butanone,
      and pyrolyzed prior to GC-MS analysis. The compounds were monitored using
      selected ion monitoring at m/z 232 and m/z 190 for acetyltelluronium and
      telluronium choline, respectively, and at m/z 236 and m/z 194 for the analogous
      deuterated internal standards. The assay was linear over a range of 20 pmol-20
      nmol of compound taken through the assay.

PMID- 8130882
TI  - Electrophoretically mediated microanalysis of ethanol.
AB  - Capillary electrophoresis was used to determine ethanol by the methodology of
      electrophoretically mediated microanalysis (EMMA). In EMMA, spatially distinct
      analyte and analytical reagent zones of differing electrophoretic mobility are
      merged under the influence of an electric field, and the resulting product is
      transported to the detector. The enzymatic oxidation of ethanol to acetaldehyde
      by alcohol dehydrogenase was utilized, and the concurrent reduction of NAD+ to
      NADH was monitored at 340 nm as a measure of the quantity of ethanol injected.
      Quantitation using an internal standard and normalization for peak migration time
      yielded a R.S.D. of 2.7%, and the linear range extended to that quantity of
      ethanol which could be reacted prior to passing by the detection window.
      Comparison of the EMMA technique to the Sigma spectrophotometric procedure
      revealed that the two methods do not yield significantly different values for the
      determination of ethanol. The EMMA method offered the advantages of
      electrophoretic mixing and miniaturization.

PMID- 8130883
TI  - Pulsatile thyrotropin and prolactin secretion in a patient with a mixed
      thyrotropin- and prolactin-secreting pituitary adenoma.
AB  - The circadian and pulsatile thyrotropin (TSH) and prolactin (PRL) release was
      investigated in a patient with slight hyperthyroidism due to a mixed TSH- and PRL
      secreting pituitary adenoma. Blood was withdrawn every 10 min for 24 h (before
      and after medical treatment); pulse characteristics were analyzed by Desade and
      Cluster programs (values as mean +/- SD). The inappropriately high mean 24-h TSH
      concentration of 3.55 +/- 0.31 mU/l was associated with a higher mean 24-h TSH
      pulse amplitude but unaltered mean 24-h TSH pulse frequency relative to healthy
      controls. The nocturnal TSH surge (absolute surge 0.5 mU/l, relative surge 16%)
      was low, related to a loss of the usual nocturnal increase of TSH pulse amplitude
      and TSH pulse frequency. Chronic treatment with octreotide resulted in a modest
      clinical and biochemical improvement of the hyperthyroid state; addition of
      bromocriptine at a later stage had no further beneficial effect. At the end of
      the follow-up period the mean 24-h TSH paradoxically had increased to 5.33 +/-
      0.81 mU/l. The nocturnal TSH surge also increased (absolute surge 1.9 mU/l,
      relative surge 42%), but circadian changes in TSH pulsatility remained absent. In
      the untreated period the increased mean 24-h PRL concentration of 234 +/- 24
      micrograms/l was associated with an increased mean 24-h PRL amplitude, whereas
      the 24-h PRL pulse frequency (N = 4) was lower relative to controls. No circadian
      PRL rhythm was present. After octreotide and bromocriptine treatment the mean 24
      h PRL concentration and mean 24-h PRL pulse amplitude were unchanged, but a clear
      nocturnal increase of PRL now was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130884
TI  - Enhanced adrenocorticotrophic hormone and cortisol responses to corticotrophin
      releasing hormone in central idiopathic diabetes insipidus.
AB  - It is well known that arginine vasopressin (AVP) exerts a stimulatory effect on
      adrenocorticotrophic hormone (ACTH) secretion. Moreover, there is consistent
      evidence that the hypothalamic AVP-secreting neurons are involved in the
      neuroregulation of ACTH secretion. With the aim to throw further light on the
      interaction between AVP and corticotrophin-releasing hormone (CRH) in the
      neuroregulation of ACTH secretion, in this study we compared the ACTH and
      cortisol responses to human CRH (100 micrograms iv as a bolus) in 18 normal
      subjects (15 females and three males, age 22-35 years) and seven patients with
      central isolated diabetes insipidus (six females and one male, age 16-40 years).
      Two patients were newly diagnosed and five had discontinued substitution therapy
      with desamino-D-AVP 24 h before testing. All had free access to water before and
      during the test period. The ACTH and cortisol responses to CRH were higher in
      subjects with diabetes insipidus than in controls, either when evaluated as peak
      values (ACTH, mean +/- SEM: 17.0 +/- 1.2 vs 7.7 +/- 0.7 pmol/l, p = 0.0003;
      cortisol: 611.3 +/- 59.4 vs 450.7 +/- 21.2 nmol/l, p = 0.01) or area under curve
      values (ACTH: 672.5 +/- 75.7 vs 364.0 +/- 33.6 pmol.l-1 x h-1, p = 0.002;
      cortisol: 29158.0 +/- 2937.0 vs 23236.7 +/- 1052.1 nmol.l-1 x h-1, p = 0.03).
      These results show that patients with diabetes insipidus have an exaggerated
      pituitary-adrenal response to CRH. This may be due to the fact that in diabetes
      insipidus AVP secretion from parvocellular neurons of the paraventricular nucleus
      in the hypophysial portal system is not impaired.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8130885
TI  - Octreotide exerts different effects in vivo and in vitro in Cushing's disease.
AB  - The effect of the long-acting somatostatin analog octreotide (SMS 201-995) on
      adrenocorticotropin (ACTH) secretion was studied in five patients with untreated
      Cushing's disease in vivo and in six human corticotropic adenoma cell cultures in
      vitro. For the in vivo study, 100 micrograms of octreotide sc was given 30 and
      180 min after cannulation of the cubital vein and 100 micrograms of corticotropin
      releasing hormone (CRH) was injected iv at 210 min. Serum ACTH and cortisol
      levels were measured for 390 min. In vivo, octreotide had no significant effect
      either on basal or CRH-stimulated ACTH levels and did not influence cortisol
      levels. The in vitro studies were conducted with corticotropic adenoma cell
      cultures derived from adenoma tissue obtained from six patients with Cushing's
      disease. In four of six cell cultures, octreotide (1 nmol/l-1 mumol/l) inhibited
      basal ACTH secretion in a dose-dependent manner. The inhibition ranged from 70 to
      92% for 1 nmol/l octreotide to 14-46% for 1 mumol/l octreotide as compared to
      controls (100%). In three of three octreotide-responsive adenoma cell cultures
      investigated. CRH-stimulated ACTH secretion was suppressed by octreotide.
      Hydrocortisone pretreatment in vitro abolished the inhibitory effect of
      octreotide on ACTH secretion in one octreotide-responsive corticotropic adenoma
      cell culture. In conclusion, we showed that octreotide in most cases could
      inhibit the ACTH release from human corticotropic adenoma cells in vitro but had
      no suppressive effect on ACTH levels of patients with Cushing's disease in vivo.
      This discrepancy could be due to a somatostatin receptor down-regulation by
      cortisol at the hypercortisolemic state in vivo.

PMID- 8130886
TI  - Deficient pulsatile thyrotropin secretion in the low-thyroid-hormone state of
      severe non-thyroidal illness.
AB  - Twenty-four-hour thyrotropin (TSH) profiles in eight severely ill patients were
      compared with those of six healthy subjects. The profiles were assessed using the
      cosinor method to evaluate circadian variations and using the Pulsar algorithm to
      analyze episodic secretion. In the normal subjects, the typical periodicity of
      TSH secretion showed a mean level in the rhythm (mesor) of 2.03 mU/l. The
      amplitude (half the extent of rhythmic change in the cycle) was 0.58 mU/l; the
      acrophase (the delay from midnight (0 degrees) of the highest level in the
      rhythm) was -9.9 degrees. In contrast, severely ill patients showed only slight
      and anticipated elevations of serum TSH levels (mesor 0.93 mU/l, amplitude 0.22
      mU/l, acrophase +82.4 degrees). Moreover, whereas the episodic TSH secretion in
      healthy individuals consisted of 5-8 pulses/24 h, mainly clustered around
      midnight, only one pulse of reduced amplitude was detected in two of the eight
      severely ill patients and no pulses in the other six. Since earlier studies have
      indicated that the loss of TSH pulsatility is associated with the relative
      insensitivity of the thyrotrophs to low thyroid hormone levels and our analytical
      procedures have demonstrated that 24 h pulsatile pattern of TSH closely
      overlapped with baseline TSH secretion, it seems reasonable to assume that low
      thyroid-hormone state, deficient pulsatile TSH secretion and altered nyctohemeral
      TSH periodicity do not coincide by chance, but that there is a causal
      relationship between such abnormalities in severely ill patients.

PMID- 8130887
TI  - Autoimmune thyroid disorders and coeliac disease.
AB  - Eighty-three patients with autoimmune thyroid disorders were screened for coeliac
      disease. The screening was performed with IgA-class reticulin and endomysium
      antibody, IgA- and IgG-class gliadin antibody tests, and various biochemical
      tests for malabsorption. None of the tested subjects had selective IgA
      deficiency, which excludes the possibility of not detecting positives by an IgA
      class test. Of the 83 patients, three asymptomatic coeliac patients were found,
      and one patient with coeliac disease previously diagnosed, an overall frequency
      of 4.8%. In addition, 25 patients with a solitary nodule of the thyroid gland
      were examined and one of them (4%) was found to have coeliac disease. By
      contrast, one (0.4%) out of 249 age- and sex-matched blood donors was found to
      have coeliac disease. All newly detected coeliac patients had IgA-class gliadin,
      reticulin and endomysium antibodies, but none of the patients had any
      gastrointestinal symptoms or abnormal biochemical findings suggesting coeliac
      disease. Treatment of thyroid disorders and coeliac disease was successful in
      these patients. The present results confirm that the frequency of subclinical
      coeliac disease is increased among patients with autoimmune thyroid disorders.
      IgA-class reticulin, endomysium or gliadin antibody tests are suitable screening
      methods for detecting these patients, as far as selective IgA-deficiency is
      excluded.

PMID- 8130888
TI  - Acute effects of intravenous 1 alpha-hydroxycholecalciferol on parathyroid
      hormone, osteocalcin and calcitriol in man.
AB  - The acute effects of a single intravenous injection of 2 micrograms of 1 alpha
      hydroxycholecalciferol (alfacalcidol) were studied for a 24-h period in six
      normal males (mean age 33 years), six women with primary hyperparathyroidism
      (mean age 72 years) and six women with established osteoporosis (mean age 63
      years). In all three groups, serum calcitriol levels rose to a peak 2-3 h after
      administration of alfacalcidol. Basal levels were highest in the primary
      hyperparathyroidism group at (mean +/- SEM) 81 +/- 2 vs 62 +/- 12 (normal males)
      (p < 0.05) and 56 +/- 5 pmol/l (osteoporosis) (p < 0.01). Highest peak levels
      were found also in the primary hyperparathyroidism group at 150 +/- 15 vs 114 +/-
      15 (normal males) (p < 0.05) and 127 +/- 15 pmol/l (osteoporosis) (p < 0.01). The
      rise in calcitriol was higher in the primary hyperparathyroidism group than
      either the normal males or osteoporotic patients (p < 0.05). No significant
      differences were evident in basal serum calcidiol concentrations among the three
      treatment groups. As might be expected, highest basal concentrations of
      parathyroid hormone (PTH), serum calcium and serum osteocalcin were noted in the
      primary hyperparathyroid group (PTH: 17.1 +/- 7.7 vs 1.9 +/- 0.5 (normal males)
      (p < 0.01) and 2.1 +/- 0.3 pmol/l (osteoporosis) (p < 0.01); calcium: 3.06 +/-
      0.08 vs 2.50 +/- 0.02 (normal males) (p < 0.01) and 2.43 +/- 0.02 mmol/l
      (osteoporosis) (p < 0.01); osteocalcin: 1.10 +/- 0.08 vs 0.56 +/- 0.16 (normal
      males) (p < 0.05) and 0.53 +/- 0.21 nmol/l (osteoporosis) (p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8130889
TI  - Estradiol regulation of mRNA expression of stimulatory G-protein alpha-subunit in
      white adipose tissue from female rats.
AB  - Adipose tissue has been recognized as a major peripheral metabolic target of
      estrogens. The present study was addressed to examine in female rats whether
      differences in the adipose tissue mRNA expression of alpha-subunit of stimulatory
      (Gs) and/or inhibitory (Gi) G-proteins exist between intact and ovariectomized
      rats, the latter with or without estradiol or testosterone treatment. The fat
      cell membrane protein amount of Gs and Gi alpha-subunit also was examined. All
      these parameters were evaluated in parametrial fat tissue samples obtained from
      40 female Sprague-Dawley rats. A group of rats (N = 20) was investigated for
      evaluation of mRNA expression and another group (N = 20) for quantification of
      the protein amount of Gs and Gi alpha-subunit. Each group was represented by five
      control rats (sham-operated), five ovariectomized (OVX) rats, five ovariectomized
      rats treated with estradiol (OVXE) and five ovariectomized rats treated with
      testosterone (OVXT). Ribonucleic acid extracted from adipose tissue and analyzed
      by northern blot with G alpha s, G alpha i-3 cRNA probes revealed three major
      bands with estimated sizes of 1.9, 3.5 and 2.35 kb, respectively. Messenger RNA
      quantitative analysis, by a solution of hybridization RNAase protection assay on
      total nucleic acid samples, showed that the amount of G alpha i-1 and G alpha i-2
      mRNA was similar within the different groups, whereas the G alpha s mRNA was
      significantly less abundant (p < 0.01) in OVX and OVXT rats than in control or
      OVXE rats. No difference in G alpha s mRNA content was found between control and
      OVXE rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130890
TI  - Calcium mobilization is a prerequisite for the expression of phorbol ester
      stimulated luteinizing hormone secretion from pituitaries of male and acutely
      ovariectomized rats.
AB  - Ionomycin, which mobilizes Ca2+, and phorbol 12-myristate 13-acetate (PMA), which
      activates protein kinase C (PKC), were used to compare the effects/interactions
      of Ca2+ and PKC on luteinizing hormone (LH) secretion from pituitaries of intact
      male and acutely ovariectomized (72 h) rats. Quartered pituitaries from donor
      animals were perifused at 0.25 ml/min and sequential effluent fractions were
      collected every 10 min. Continuous administration (4 h) of 1 nmol of gonadotropin
      releasing hormone (GnRH) resulted in an increase in LH secretion. Cycloheximide
      (5 mumol) dissociated the GnRH-stimulated LH responses into protein synthesis
      independent and -dependent components. While ionomycin (10 mumol) stimulated LH
      secretion from pituitaries of both sexes by protein synthesis-independent
      mechanisms, PMA (1 mumol) and the inactive phorbol ester, 4 alpha-phorbol 12,13
      didecanoate (PDD), were ineffective secretagogues. However, PMA (but not PDD)
      interacted synergistically with ionomycin and GnRH to augment LH secretion by
      protein synthesis-dependent mechanisms. These results suggest a similarity in the
      effects/interactions of Ca2+ and PKC in gonadotropes from male and ovariectomized
      rats. If the effects of PMA can be attributed to PKC activation, then it also
      appears that Ca2+ mobilization is necessary for the manifestation of PKC as a
      mediator of LH secretion from these gonadotropes. While PKC activity can be
      divorced from the protein synthesis-independent component of LH release (this
      component appears to be mediated by Ca2+ mobilization), the enzyme might be
      involved in amplifying the response to Ca2+ mobilization through synergistic
      protein synthesis-dependent mechanisms.

PMID- 8130891
TI  - Progesterone stimulates fibronectin production by chicken granulosa cells in
      vitro.
AB  - Experiments were conducted in vitro to examine the effect of progesterone on
      fibronectin production by chicken ovarian granulosa cells. Granulosa cells
      isolated from the largest (F1; mature) and third-largest (F3; developing)
      preovulatory follicles as well as form a pool of immature small yellow follicles
      (SYF) of the domestic chicken ovary were incubated in serum-free Medium-199 and
      the amounts of fibronectin and progesterone produced were quantified by enzyme
      linked immunosorbent assay and radioimmunoassay respectively. The amounts of
      basal fibronectin and progesterone produced by granulosa cells from F1, F3 and
      SYF follicles increased with advancing stages of follicular development. Thus,
      the quantity of basal fibronectin secreted by granulosa cells was directly
      proportional to the amount of progesterone produced by them. Exogenously supplied
      progesterone increased the amount of fibronectin secreted by F1 and F3 cells in a
      dose-dependent manner, but its effect on SYF cells was marginal. Cyanoketone (an
      inhibitor of progesterone synthesis) suppressed basal fibronectin production by
      F1 and F3 granulosa cells and its inhibitory action was reversed by exogenous
      progesterone. The progesterone antagonist RU 486 also attenuated basal
      fibronectin production by F1 and F3 granulosa cells, but only the highest
      concentration affected SYF cells. The inhibitory effect of RU 486 was diminished
      in the presence of exogenous progesterone. These data show that progesterone
      regulates fibronectin production by chicken granulosa cells. They suggest that in
      avian granulosa cells, endogenous progesterone can stimulate fibronectin
      synthesis in an intracrine or autocrine manner.

PMID- 8130892
TI  - Stimulation of sex hormone-binding globulin mRNA and attenuation of
      corticosteroid-binding globulin mRNA by triiodothyronine in human hepatoma cells.
AB  - We examined the time course and dose response of the triiodothyronine (T3) effect
      on mRNAs for sex hormone-binding globulin (SHBG) and corticosteroid-binding
      globulin (CBG) in cells of the human hepatoma line HepG2. After 7 h of exposure
      to a saturating dose of T3, SHBG mRNA was unchanged but increased to 1.5 +/- 0.1
      times the unstimulated control at 22 h. Maximal stimulation (2.3 +/- 0.6) was
      observed at 2-3 days. Corticosteroid-binding globulin mRNA was unchanged for 22 h
      after exposure to T3 but diminished thereafter to 64% by day 3. At 3-4 days of
      exposure, the changes in both SHBG mRNA and CBG mRNA were dose-responsive to the
      T3 concentration. For both mRNAs, half-maximal response occurred between 10 and
      20 pmol/l bioavailable T3. Cortisol-binding proteins secreted by HepG2 cells
      after 3 days in culture also were T3 dose-responsive. No re-uptake of secreted
      CBG by the cells was observed, suggesting that the T3 effect on CBG secretion
      occurs during production of the mature protein. These data suggest that T3
      stimulates the expression of the SHBG gene and attenuates the expression of the
      CBG gene. The effects of T3 on these genes are consistent with the increase in
      circulating SHBG and decrease in circulating CBG observed in hyperthyroidism. The
      HepG2 cells may be a useful human cell line in which to study the diversity of
      the molecular mechanisms of T3 action.

PMID- 8130893
TI  - L-triiodothyronine acutely increases Ca2+ uptake in the isolated, perfused rat
      heart. Changes in L-type Ca2+ channels and beta-receptors during short- and long
      term hyper- and hypothyroidism.
AB  - Acutely administered triiodothyronine (T3) in supraphysiological doses has been
      shown to exert an acute positive inotropic effect in vivo a few minutes after
      intravenous administration. To investigate whether this effect could be explained
      by an acutely increased Ca2+ uptake in the myocardium, an isolated perfused rat
      heart model ad modum Langendorff was established. The acute stimulative effect of
      T3 on myocardial Ca2+ uptake was determined indirectly by measuring changes in
      Ca2+ concentration in the perfusate following coronary perfusion with 45Ca(2+)
      containing buffer. Perfusion with T3 gave rise to dose-dependent reductions in
      perfusate Ca2+ within 20 s. Following 10(-9) and 10(-11) mol/l T3, the effect was
      small and usually lasted less than 1 min. Perfusion with 10(-6) and 10(-7) mmol/l
      T3 resulted in a decrease in perfusate Ca2+, which remained stable throughout 4-6
      min of observation. Calcium channel blockade with nifedipine prevented the
      decrease in perfusate Ca2+, suggesting that voltage-operated Ca2+ channels are
      involved in the increased Ca2+ uptake. A washout period with T3-free buffer re
      established the Ca2+ concentration in the perfusate, suggesting that the effect
      is reversible. Calcium channels have been suggested to be regulated directly by
      T3. Maximum binding capacities for myocardial Ca2+ channels and beta-receptors
      were determined by binding studies with [3H]PN200-110 and [125I]iodocyanopindolol
      in short-term and long-term hyper- and hypothyroid rats. After 2 and 8 weeks,
      Ca(2+)-channel maximum binding capacities were reduced by 25% and 23% in
      hyperthyroid rats (p < 0.05) and increased by 33% and 23% in hypothyroid rats (p
      < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130894
TI  - Effect of P1-purinergic agonist on thyrotropin stimulation of H2O2 generation in
      FRTL-5 and porcine thyroid cells.
AB  - Our previous studies have shown that the generation of H2O2 in FRTL-5 thyroid
      cells is regulated via both the adenylate cyclase/cyclic adenosine monophosphate
      (cAMP) and Ca2+/phosphatidylinositol pathway: thyrotropin (TSH) stimulates H2O2
      generation through both pathways, via the former at a low concentration and via
      the latter at a high concentration. In porcine thyrocytes in primary culture H2O2
      generation is stimulated only via the Ca2+/phosphatidylinositol route. In the
      present study we explored the effect of a P1-purinergic agonist
      (phenylisopropyladenosine, PIA) on stimulations induced by TSH and by adenosine
      triphosphate (ATP), an activator of the Ca2+/phosphatidylinositol cascade via the
      P2-purinergic receptor. In FRTL-5 cells, PIA potentiated H2O2 generation
      stimulated by TSH at 10 U/l (but not at 1 U/l, Ca2+ mobilization induced by TSH
      and Ca2+ mobilization induced by ATP at 1 mumol/l (but not 10 mumol/l).
      Phenylisopropyladenosine strongly inhibited TSH-induced cAMP accumulation in FRTL
      5 cells. In pig thyrocytes, PIA had no effect on H2O2 generation stimulated by
      TSH or ATP and no effect on ATP-stimulated Ca2+ mobilization. Also, PIA did not
      inhibit TSH-stimulated cAMP accumulation in pig thyrocytes, and by itself had no
      effect on H2O2 generation or Ca2+ mobilization. Thus, in FRTL-5 cells, but not in
      porcine thyrocytes, PIA modulates TSH-stimulated H2O2 generation by enhancing the
      Ca2+/phosphatidylinositol route and inhibiting the adenylate cyclase/cAMP route
      of the TSH signal. The net result of this modulation apparently depends on the
      balance between inhibition of the cAMP route and enhancement of the Ca2+ route.
      This may explain the lack of potentiation observed by 1 U/l TSH.

PMID- 8130895
TI  - Enhanced cell proliferation by hyperprolactinemia in both exocrine and endocrine
      pancreas in mice.
AB  - Effects of hyperprolactinemia induced by ectopic anterior pituitary grafting on
      the pancreas were studied in male SHN mice. After pituitary grafting, the weight
      of pancreas rapidly increased. A similar increase in pancreatic weight was
      observed during lactation, a condition associated with elevated prolactin levels.
      Results of DNA and protein assays revealed that the increase in pancreatic weight
      in both pituitary-grafted and lactating mice was mainly due to the increase in
      the cell number, because the total DNA content per pancreas was greater in these
      mice than the controls. An increase in fluid volume or hypertrophy of cells also
      contributes to the weight increase; in contrast, the DNA and protein contents per
      unit tissue weight decrease. The rate of DNA synthesis determined by 5-bromo-2'
      deoxyuridine labeling was higher both in acinar cells and islet B cells in
      pituitary-grafted mice than in the controls. Thus, hyperprolactinemia stimulates
      cell proliferation in exocrine pancreas as well as endocrine islets. The effect
      of prolactin seems to be indirect on acinar cells, because only B cells showed
      prolactin immunoreactivity in the mouse pancreas. In addition, insulin might not
      be a mediator of the prolactin effect on acinar cells, because the serum insulin
      level in pituitary-grafted mice failed to show any change.

PMID- 8130896
TI  - Effect of the antiglucocorticoid RU486 on adrenal steroidogenic enzyme activity
      and steroidogenesis.
AB  - RU486, a synthetic steroid receptor antagonist, has strong antiprogesterone and
      antiglucocorticoid properties. Chronic RU486 administration in two patients with
      ectopic secretion of adrenocorticotropin (ACTH) has been associated with
      decreasing plasma cortisol concentrations. One explanation of this finding is
      that RU486 may directly inhibit adrenal steroidogenesis. To test this hypothesis,
      we measured the effect of RU486 on specific steroidogenic enzymatic steps using
      an in vivo rat and an in vitro monkey model. Hypophysectomized-castrated-ACTH
      replaced Sprague-Dawley rats were given RU486 i.p. at daily doses of 0, 0.0005,
      0.005, 0.05, 0.5 and 5 mg/kg body weight per day for 7 days. The animals were
      sacrificed, and blood and adrenal glands collected. Adrenal cortical mitochondria
      and microsomes were purified from the rats and from two untreated Cynomolgus
      macaque monkeys. Specific steroidogenic enzyme activities were measured in the
      rat by the incorporation of 14C-labeled steroid substrates into products. A
      similar protocol was used to assay the steroidogenesis in the monkey adrenal
      fractions in the presence and absence of added RU486. Although rat adrenal
      weights decreased significantly at the highest RU486 dose, plasma levels of
      corticosterone were similar in control and treated rats. Rat adrenal 3 beta
      hydroxysteroid dehydrogenase/isomerase (3-HSD), 21-hydroxylase (21-OH) and 11
      hydroxylase (11-OH) activities decreased with increasing RU486 doses, with 21-OH
      and 11-OH being most severely affected. Monkey adrenal 3-HSD, 21-OH, 11-OH, 17
      hydroxylase and 17,20-desmolase similarly decreased in the presence of increasing
      in vitro concentrations of RU486.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130897
TI  - Human parathyroid hormone(1-34) increases bone formation and strength of cortical
      bone in aged rats.
AB  - The effect of parathyroid hormone (PTH(1-34)) on mid-diaphyseal femoral cortical
      bone was studied in 2-year-old male rats. The rats were treated with daily
      injections of 15 nmol/kg PTH(1-34) or vehicle for 56 days, and labelled with
      tetracycline and calcein on day 15 and day 40, respectively. The PTH(1-34)
      treatment did not affect the body weights or the lengths of the femora.
      Fluorescence microscopy showed large intracortical cavities in the old vehicle
      treated rats. After PTH treatment, double labelling and new bone formation
      filling in these cavities were found. Furthermore, an increased bone formation
      rate was observed both at the periosteum and at the endosteum. This resulted in
      an increase in the cross-sectional area and a decrease in the medullary area.
      Three-point bending analysis revealed an increase in ultimate load, ultimate
      stiffness, energy absorption and ultimate stress after the PTH(1-34) treatment.
      No differences were found between the groups regarding the hydroxyproline
      concentration or apparent and real densities. The ash concentration was, however,
      slightly reduced after PTH(1-34) treatment. The PTH(1-34) treatment of old rats
      induced the formation of bone both from the periosteum and endosteum, with a
      pronounced filling in of intracortical cavities, and, furthermore, a marked
      increase in the biomechanical competence of the cortical bone.

PMID- 8130898
TI  - Low-dose interleukin 1 and tumor necrosis factor individually stimulate insulin
      release but in combination cause suppression.
AB  - The macrophage-derived cytokines interleukin 1 (IL-1) and tumor necrosis factor
      (TNF) have direct effects on pancreatic beta cells and have been hypothesized to
      play important roles in the autoimmune beta cell lesion of type I diabetes
      because of two major effects on beta cells: altered insulin secretion and beta
      cell cytotoxicity. High doses of IL-1 are cytotoxic to beta cells and strongly
      inhibit insulin release; high-dose IL-1 plus TNF acts synergically to suppress
      further the insulin release. In contrast, we observed that the predominant effect
      of low-dose IL-1 and TNF when administered separately was the stimulation of
      insulin release. We therefore asked whether the combination of low-dose IL-1 plus
      TNF would act synergistically to stimulate or suppress insulin release. Studies
      were performed on cultured rat islets and both insulin release and cytotoxicity
      (51Cr release) were measured. After 2 days of culture, increasing doses of IL-1
      25, 50, 75 and 100 ng/l--caused progressively increased cytotoxicity and impaired
      insulin release. In contrast, the lowest dose of IL-1 tested, 10 ng/l, increased
      insulin release but was still slightly cytotoxic. Tumor necrosis factor at doses
      of 10, 25, 62.5, 75 and 100 micrograms/l also was slightly cytotoxic but
      increased insulin release. The augmented insulin release declined progressively
      with increasing TNF dose. However the combination of insulin stimulatory doses of
      IL-1 (10 ng/l) and TNF (62.5 micrograms/l) suppressed insulin release. The
      effects of these two cytokines on insulin release demonstrated a similar pattern
      after 4 and 6 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130899
TI  - Exercise tolerance test: the decision to refer.

PMID- 8130901
TI  - The doctor will fix it.

PMID- 8130900
TI  - Homosexuality does not cause acquired immunodeficiency syndrome.

PMID- 8130902
TI  - Human papillomavirus. To screen or not to screen.

PMID- 8130903
TI  - The routine antenatal diagnostic imaging with ultrasound study. The challenge to
      practice evidence-based obstetrics.

PMID- 8130904
TI  - The shortage of generalist physicians and federal funding of graduate medical
      education.
AB  - Graduate Medical Education (GME) payments through the Health Care Financing
      Administration (HCFA) represent the largest portion of federal funding in direct
      support of training for health professionals. Whatever the benefits of these
      funds, they clearly have not served as a positive factor in addressing the
      emerging shortfall of generalist physicians. Therefore, a variety of options are
      being discussed for restructuring the incentives associated with HCFA GME funds.
      Seven principal alternatives that have been proposed to address these problems
      are the following: modification of hospital GME payments, GME payments to medical
      schools, GME payments to residency programs, GME transfers through Medicare part
      B, GME transfers to the Health Resources and Service Administration, GME
      transfers to states through block grants, and GME payments to academic consortia.
      Unfortunately, each of these approaches offers substantial disadvantages and
      faces important opposing constituencies. To address these weaknesses, combined
      strategies and "all payor" federal mechanisms of GME financing have recently been
      proposed. These compromise approaches have their own administrative and political
      liabilities as well. Revisions in current HCFA GME payments may be preferable as
      a first step, but more comprehensive approaches involving all payor financing
      with mechanisms that reconnect medical school training with primary care practice
      will likely be required to ensure efficient and effective reform. Such major
      shifts in the federal funding of GME will not be quick in coming, however, and
      will doubtless be characterized by a compromise of policy effectiveness with
      political feasibility.

PMID- 8130905
TI  - Factors associated with human papillomavirus infection in women encountered in
      community-based offices.
AB  - OBJECTIVE: To assess risk factors for cervical human papillomavirus (HPV)
      infection in women presenting to community-based offices because of vaginal
      symptoms or for preventive screening. DESIGN: Cross-sectional analysis of
      history, physical examination, and microbiological infection variables. SETTING:
      Two community-based family practice offices in southeastern Michigan. PATIENTS:
      Two hundred seventy-three women, 18 to 50 years of age, presenting to the study
      sites because of vaginal symptoms or for a pelvic examination for preventive
      screening. MAIN OUTCOME MEASURE: Human papillomavirus infection of the uterine
      cervix as determined by polymerase chain reaction testing. RESULTS: Human
      papillomavirus infection was detected in 21.2% of the women (24.9% and 13.1% of
      women with and without vaginal symptoms, respectively); 34% of these infections
      were HPV types 16 or 18. Fifty-four percent of the women with HPV infection who
      underwent colposcopy had condyloma or cervical intraepithelial neoplasia verified
      on biopsy. Independent associations were found between HPV infection and the
      following female risk factors: the presence of vaginal itching, odor, or
      swelling; knowing the current sexual partner less than 24 months; age less than
      40 years; household income of $14,000 or less; and ever having had six or more
      sexual partners. CONCLUSIONS: In addition to three previously described risk
      factors for genital HPV infection, two previously unrecognized risk factors were
      identified in this lower-risk population. These risk factors included the
      presence of vaginal symptoms of itching, odor, or swelling and having known the
      current sexual partner less than 24 months. Nevertheless, using risk factors
      alone, two thirds of the women infected with HPV in this population were not
      identified as being at high risk of infection. No subset of sexually active women
      was identified who were at no risk of HPV infection.

PMID- 8130906
TI  - Presence of human papillomavirus infection of the uterine cervix as determined by
      different detection methods in a low-risk community-based population.
AB  - OBJECTIVE: To evaluate the effectiveness of various screening tests for detecting
      genital human papillomavirus (HPV) in a community-based population and to
      determine the prevalence of cervical lesions on colposcopically directed biopsies
      in patients found to have HPV by any screening test. DESIGN: Cross-sectional
      analysis of 208 female patients screened for HPV by clinical examination,
      Papanicolaou test, dot blot hybridization test (ViraPap, Digene Inc, Silver
      Spring, Md), and polymerase chain reaction (PCR) analysis. All persons with
      abnormal or positive results by any method were offered colposcopic evaluation.
      SETTING: Two community-based family practice offices in southeastern Michigan.
      MAIN OUTCOME MEASURES: The presence of HPV as determined by each test and results
      of colposcopic biopsies (gold standard) in patients who had HPV identified by any
      test. RESULTS: The prevalence of HPV infection was 20.3% by PCR analysis, 3.1% by
      ViraPap, 3.0% by the Papanicolaou test, and 0% by clinical examination.
      Symptomatic patients (those with complaints of vaginal odor, swelling, or
      itching) were more likely to harbor HPV as determined by PCR analysis than were
      asymptomatic women (P = .03, odds ratio = 2.65). Human papillomavirus type 16 or
      18 was found in 41% of patients with positive PCR analyses and in all patients
      with positive ViraPap tests that were typed. Colposcopy with biopsy (gold
      standard for the presence of HPV disease) was performed on 34 of the 41 patients
      who tested positive for HPV by PCR analysis. Histologic results revealed that
      79.4% of these patients had cervical disease: 14.6% had cervical intraepithelial
      neoplasia, 38.3% had condyloma, and 26.5% had cervicitis. CONCLUSIONS: Human
      papillomavirus as detected by PCR analysis was present in 20.3% of women in our
      population and was often one of the higher-risk types (16 or 18). A positive PCR
      analysis was predictive of cervical disease on colposcopic biopsy. The ViraPap
      test, Papanicolaou test, and clinical examination were insensitive measures for
      detecting HPV-related lesions in this population.

PMID- 8130907
TI  - Self-reported alcohol use among women of childbearing age and their knowledge of
      alcohol warning labels and signs.
AB  - OBJECTIVE: To examine the prevalence of self-reported alcohol use among women of
      childbearing age and their ability to recall information about pregnancy risk
      contained in warning labels on alcoholic beverage containers and warning signs
      posted in places where liquor is sold. DESIGN: A telephone survey was conducted
      with adults using a dual-frame procedure. Specifically, approximately one third
      of the total sample were contacted by random-digit dialing, and the remainder
      were obtained from listed residential telephone numbers. Also, poststratification
      weighting was done using estimates of age, ethnic, and sex groups to approximate
      the 1990 adult population of Illinois. SETTING: A total of 4987 adults with known
      residence (excluding those without residences and/or telephones and those living
      in institutions or group quarters) in Illinois participated in a survey during
      the spring and summer of 1990. PARTICIPANTS: A total of 1515 women of
      childbearing age (18 through 45 years old) participated in the survey. A random
      subsample of approximately half were asked questions regarding warning labels and
      signs; the other half were omitted from the investigation, which yielded the
      final sample of 748. MAIN OUTCOME MEASURES: The two main outcome measures were
      self-reported alcohol use and ability to recall information about pregnancy risk
      contained in warning labels and signs. RESULTS: Pregnant women were significantly
      less likely than nonpregnant women to report using alcohol in the past 30 days.
      Approximately one fourth of all women were able to recall information about
      pregnancy risk contained in warning labels and signs. CONCLUSIONS: Alcohol
      warning labels and signs seem to be reaching a minority of women; this was
      uniform across several sociodemographic subpopulations, with few exceptions.

PMID- 8130908
TI  - The influence of gender and race on mean body temperature in a population of
      healthy older adults.
AB  - Body temperature is known to vary with environmental conditions, physical
      activity, and illness. There is also some suggestion that body temperature is
      higher in women than men, and higher in blacks than whites. This study was
      undertaken to determine if previously described differences in body temperature
      found in relatively uncontrolled settings associated with gender and race can be
      reproduced under carefully controlled conditions. Temperature was measured orally
      with calibrated mercury-in-glass thermometers in 92 healthy community-dwelling
      volunteers aged 64 years and older. Environmental conditions were carefully
      controlled and patients with physical conditions or medication regimes known to
      alter body temperature were excluded. The mean body temperature for all subjects
      was 36.86 degrees C +/- 0.23 degrees C. The means for white men and women did not
      differ significantly. There was a statistically significant difference between
      black and white women, with blacks having 0.13 degrees C higher temperature. We
      conclude that body temperature varies with race in older women. No significant
      gender-related difference in normal body temperature was found in these healthy
      elderly white men and women. Differences in body temperature between men and
      women found in younger patient populations may reflect the temperature elevations
      in women associated with menstruation.

PMID- 8130909
TI  - Attitudes of family physicians to nonconventional therapies. A challenge to
      science as the basis of therapeutics.
AB  - Eighty-nine Israeli family physicians responded to a questionnaire on their
      experience with nonconventional therapies (NCTs) and their opinions about the
      scientific basis and clinical efficacy of these treatments. They were also asked
      whether they thought that NCTs should be incorporated into regular medical
      practice. Seventeen percent of the physicians had formal training in some form of
      NCT and 11% thought the scientific basis of these treatments was sound; however,
      a majority (54%) thought they may be clinically useful. Forty-two percent had
      referred patients for such treatments. The majority thought that NCTs should be
      incorporated into medical practice. Our survey suggests that many physicians are
      not using the tools of scientific critical appraisal in forming their views on
      NCTs.

PMID- 8130910
TI  - The attitudes of family physicians toward the peer review process.
AB  - We conducted a study to determine family physicians' attitudes and perceptions
      toward current peer review practices, and to discover if family physicians,
      general surgeons, and hospital-based physicians view the process differently. A
      survey instrument measured perceptions of physicians on the following four areas
      of the peer review process: (1) how peer reviews are administered, (2) the
      educational value of peer reviews, (3) the performance of peer review committees,
      and (4) the effect of the peer review process on physician morale. The survey was
      mailed to all 3528 practicing physicians who were members of a state medical
      society. A subgroup of 1695 family physicians, general surgeons, and hospital
      based physicians was used for this study, of whom 774 (46%) responded to the
      questionnaire. Over one half of the family physicians responded negatively toward
      the peer review process on all items of the survey, with over 70% dissatisfied on
      five of the 17 items. Family physicians, general surgeons, and hospital-based
      physicians viewed the peer review process differently in the four areas measured.
      We found statistically significant differences of opinions regarding present peer
      review practices among the specialties cited. However, the overall
      dissatisfaction of the specialty groups studied may suggest that the concern
      resides more with the profession at large than with any one medical specialty
      group.

PMID- 8130911
TI  - Current models for clinical ethics consultation reimbursement.
AB  - The author reviewed the literature on compensation for ethics consultation and
      undertook an informal telephone survey of 33 nationally prominent clinical ethics
      consultants in American health care institutions and medical schools in late fall
      1992. Twenty-nine (88%) of 33 consultants responded. Most donate their time when
      asked to consult and are not paid directly for consultation services. Other
      ethics consultants, however, provide services to colleagues and patients and are
      compensated by private practice billing, salaried arrangements, and income from
      ethics training programs. Salaried arrangements through managed-care
      organizations seem to hold the greatest promise for ethics consultants who wish
      to be paid, although such arrangements raise ethical issues themselves. To be
      paid at all, ethics consultants called on by family physicians to see patients
      may be asked to balance institutional cost-effectiveness with the personal
      bedside process of ethics consultation.

PMID- 8130912
TI  - Patient abuse in rural midwestern pregnant women?

PMID- 8130913
TI  - Older women's health. Avoiding a tragedy of mythic proportions.

PMID- 8130914
TI  - Gender differences in coronary artery disease. Bias, method, or fact of life?

PMID- 8130915
TI  - Ambulatory quality management. A call for articles.

PMID- 8130917
TI  - Glucose.

PMID- 8130916
TI  - Diagnostic and treatment guidelines on elder abuse and neglect.
AB  - It is estimated that between 1.5 and 2 million older adults experience abuse or
      neglect each year in the United States. Elder mistreatment may be physical,
      psychological, or financial, and it may be perpetrated by family members or by
      other informal or formal caregivers. Physicians are encouraged to play an active
      role in assessment, intervention, and prevention.

PMID- 8130918
TI  - Family function, stress, and locus of control. Relationships to glycemia in
      adults with diabetes mellitus.
AB  - OBJECTIVE: To determine whether glycemic control in adults with either insulin
      dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus
      (NIDDM) is related to perceived family function, stress/coping, affect, and locus
      of control. DESIGN: Cross-sectional, observational study. PARTICIPANTS: Four
      hundred seven subjects from a family medicine ambulatory care unit, a tertiary
      pediatric diabetic unit, or a public-funded community health center, all located
      in Winston-Salem, NC, completed a series of psychometric instruments that
      included the Family APGAR (Adaptation, Partnership, Growth, Affection, and
      Resolve), FACES III (Family Adaptability and Cohesion Evaluation Scales) Cohesion
      subscale, Affect Balance Scale, Multidimensional Health Locus of Control Scales,
      and the Brief Encounter Psychosocial Instrument. MAIN OUTCOME MEASURE: Glycemic
      control was measured by fasting blood glucose levels and glycosylated hemoglobin
      A1C levels as well as by patients' perception of their control. RESULTS: Those
      with NIDDM had scores indicative of more external sources of control than those
      with IDDM. A greater proportion of adults with both subtypes of diabetes
      perceived their families to be disengaged than subjects from families without
      diabetes. In a bivariate analysis, family dysfunction correlated with lack of
      perceived glycemic control, while perceived stress and negative affect correlated
      with fasting glucose levels in those with NIDDM but not those with IDDM. Using
      multivariate discriminant analysis, adults with NIDDM in good glycemic control as
      measured by glycosylated hemoglobin levels had lower family cohesion and negative
      affect than those in poor control. Conversely, those with IDDM with acceptable
      glycosylated hemoglobin levels had higher family cohesion, less negative affect,
      fewer chance loci of control, but higher perception of inadequate coping than
      those in poor control. CONCLUSIONS: Knowledge of the family function, affect,
      locus of control, perceived stress, and coping may be useful to the family
      physician in the care of adults with diabetes mellitus, since these psychosocial
      parameters are associated with objective and perceived glycemic control.

PMID- 8130919
TI  - Asphyxial deaths due to physical restraint. A case series.
AB  - OBJECTIVE: To assess the common factors and the pattern of deaths related to the
      use of physical restraints. DESIGN: Case series. PARTICIPANTS: The chief death
      investigators of 37 large jurisdictions were sent questionnaires for all cases of
      restraint-related deaths. Sixty-three questionnaires from 23 jurisdictions were
      returned. MEASURES: The questionnaires allowed us to determine the restraint type
      used, the age and sex of the deceased, the furniture type with which restraints
      were used, the type of facility where the deceased was restrained, and whether
      the application of restraints was incorrect. RESULTS: We report 63 cases of
      asphyxial deaths from the use of physical restraints. Ages of decedents ranged
      from 26 weeks to 98 years. The greatest number of deaths occurred in the 80- to
      89-year-old patients. There is a higher frequency for females of all ages, but
      the distribution for males and females is roughly the same for all age groups.
      Deaths occurred while the patient was restrained in a chair (wheelchair or
      geriatric recliner) or a bed. Most chair-related deaths (six of 19) and bed
      related deaths (16 of 42) involved the use of vest restraints. Thirteen of the 42
      bed-related deaths involved bedrails. The majority of deaths (61%) occurred in
      nursing homes and 57 of these 63 cases occurred while restraints were properly
      applied. CONCLUSIONS: Our report of 63 cases is an underrepresentation of the
      true number of restraint deaths. Our finding that the vast majority of restraint
      deaths occurred while restraints were correctly applied implies an inherent
      danger in the use of physical restraints. The safety of restraining patients and
      the efficacy of physical restraint needs to be examined and alternate means of
      assuring the safety of patients need to be developed.

PMID- 8130920
TI  - Liver function test abnormalities in early Lyme disease.
AB  - OBJECTIVE: Lyme disease is a widespread, tick-borne, spirochetal infection with
      multiple organ system involvement Hepatic dysfunction has not been emphasized in
      the literature. We report clinical findings and laboratory abnormalities in 73
      patients with the pathognomonic erythema migrans rash early in the course of the
      illness. DESIGN: Case series. SETTING: Offices of family physicians in private
      practice and the model offices of a family practice residency program in the
      lower Connecticut River valley, an area to which Lyme disease is endemic.
      PATIENTS: Thirty-seven female and 36 male patients with erythema migrans who had
      not yet been treated with antimicrobial agents. MAIN OUTCOME MEASURE: Liver
      function tests. RESULTS: Twenty patients (27%) had liver function abnormalities.
      Elevation of gamma-glutamyltransferase was the most common finding. Only seven
      patients (9%) had a positive titer in response to the enzyme-linked immunosorbent
      assay for Lyme disease. Other laboratory and clinical findings are described.
      CONCLUSION: Subclinical hepatitis is a common finding in early Lyme disease.

PMID- 8130921
TI  - Transdermal nicotine patches with low-intensity support to aid smoking cessation
      in outpatients in a general hospital. A placebo-controlled trial.
AB  - OBJECTIVE: To assess whether transdermal nicotine patches combined with low
      intensity support can help outpatients in a general hospital stop smoking.
      DESIGN: Randomized, double-blind, placebo-controlled trial with 12 weeks of
      follow-up. SETTING: Department of Thoracic Medicine in an inner-city public
      general hospital, London, England. SUBJECTS: Two hundred forty-eight outpatients
      in a general hospital, who smoked at least 10 cigarettes per day (the majority
      were being treated for smoking-related diseases), referred by clinicians at the
      hospital. INTERVENTION: Brief advice to stop smoking and daily application of
      transdermal nicotine patches (delivering 15 mg over 16 hours) or placebo, with
      follow-up appointments at 1, 3, 6, and 12 weeks, with a doubling of the dosage
      for continuing smokers at week 1. MAIN OUTCOME MEASURE: Sustained abstinence from
      tobacco from week 3 to week 12 validated with measurement of expired-air carbon
      monoxide concentration at weeks 3, 6, and 12. RESULTS: Twenty-nine (23.4%) of 124
      subjects assigned to the nicotine group were validated as having abstained from
      smoking at both weeks 3 and 6, compared with 16 (12.9%) of 124 subjects receiving
      placebo (P = .008). At week 12, 22 (17.7%) of the subjects in the nicotine group
      were validated as having abstained at all three points as were 15 (12.1%) of the
      subjects in the placebo group (P = .058). CONCLUSION: Transdermal nicotine
      patches combined with low-intensity support are effective in helping outpatients
      in a general hospital stop smoking but do not prevent relapse after 6 weeks.

PMID- 8130922
TI  - Issues in the provision of health care to Soviet emigrants.
AB  - Political and economic unrest in the former Soviet Union has been associated with
      an influx of refugees to the United States. The medical staff at our health
      maintenance organization perceived health care provision to the Soviet refugees
      as a goodwill opportunity, but soon realized that providing health care to this
      subpopulation of patients was very difficult. This was often related to cross
      cultural differences regarding disclosure of medical information to the patient,
      acute care provision, and payment systems. Immigrants' expectations of US
      medicine are incredibly high. The interpreter plays a key role in facilitating
      communication between the health care team and the immigrant, yet the use of an
      interpreter has several inherent problems. Recognition of the problems and
      knowledge of the cross-cultural differences will likely improve rapport between
      health care personnel and immigrants.

PMID- 8130923
TI  - Carisoprodol as a drug of abuse.
AB  - Carisoprodol (available as Soma and in other commercial forms) is a commonly
      prescribed muscle relaxant. A small group of patients was recently discovered
      colluding to obtain the drug under false pretenses for the purposes of substance
      abuse. Animal and human studies have previously shown limited potential for
      tolerance or abuse, while the evidence for therapeutic efficacy is inadequate.
      There are two previous case reports of human carisoprodol abuse or dependence,
      one in which a patient showed signs of a true withdrawal syndrome. A third case
      involved a fatality linked to carisoprodol abuse. Data from the National
      Institute on Drug Abuse reveal that overdose and abuse of carisoprodol may be
      more common than previously suspected. Carisoprodol use should be limited to
      short-term treatment of acute musculoskeletal conditions involving significant
      muscle spasm. Suspicions of abuse should be raised by patients requesting the
      drug by name, "losing" prescriptions, using carisoprodol chronically, or denying
      the efficacy of less mind-altering alternatives.

PMID- 8130924
TI  - Severe asthma and depression.
AB  - The comorbidity of severe asthma and depression is frequent and complicates the
      patient's comprehensive medical management. Asthma and depression are thought to
      interact to worsen both conditions, especially at the severe end of the spectrum
      of disease. This article reviews the current thinking regarding the synergistic
      effect of the two disorders, highlighting the importance of considering both
      disorders in the comprehensive management of severe asthma. Outpatient management
      and treatment issues addressed include the use of screening/case-finding tools,
      medication management, physician counseling, and referral.

PMID- 8130925
TI  - Drug prescribing for the elderly.
AB  - Both the geriatric population of the United States and the use of prescription
      drugs by this age group continue to increase. Cardiovascular medicines,
      analgesics, anti-inflammatories, and psychotropic medications are used most
      commonly. Polypharmacy, defined as a condition in which a patient receives too
      many drugs, drugs for too long, or drugs in exceedingly high doses, often
      results.

PMID- 8130926
TI  - Ensuring the health of the adolescent athlete. Council on Scientific Affairs,
      American Medical Association.
AB  - There are an estimated 3.3 million boys and 1.8 million girls participating in
      interscholastic athletics. Although the preparticipation athletic examination
      (PAE) has traditionally focused on ensuring the health of the athlete, there has
      been growing interest in using the PAE to also screen adolescents for their
      involvement in health-threatening behaviors, such as smoking, drinking, drug use,
      and unsafe sexual practices. For 80% to 90% of adolescents, the PAE substitutes
      for a routine physical examination. Adolescent athletes may use alcohol and other
      drugs for three reasons: (1) They experiment with alcohol and other drugs as part
      of the larger youth culture. (2) They use ergogenic agents to enhance their
      athletic performance. (3) They use diuretic agents, emetic agents, or other
      excessive mechanisms to control weight. The American Medical Association
      concludes that administration of the PAE is an appropriate time to investigate
      involvement in health-risk behaviors and to provide adolescent health
      information.

PMID- 8130927
TI  - Heterogeneity among neuroepithelial cells in the chick retina revealed by
      immunostaining with monoclonal antibody PM1.
AB  - Neuroepithelial cells appear as a homogeneous population of cells in the cell
      cycle that seem to behave as pluripotent neural precursors. The study of the
      intrinsic heterogeneity and subtle developmental changes among neuroepithelial
      cells has been hindered by the lack of specific markers. To address that study, a
      panel of monoclonal antibodies was produced against early developing chick
      retina. The monoclonal antibody precursor marker 1 (PM1) labels most, if not all,
      of the early neuroepithelial cells in embryonic day 4 retinal sections. This
      pattern is transient since the labelling becomes restricted to the peripheral
      retina as development proceeds and eventually disappears from the neuroepithelial
      cells. However, apparently in parallel, the differentiating retinal ganglion
      cells become PM1-positive. The expression of the PM1 antigen, a 73 x 10(3) M(r)
      protein, as shown by western blotting, also decreases with development. In
      addition, a chick retina dissociated-cell culture system, where retinal
      neuroepithelial cells actively proliferate and undergo differentiation under
      defined conditions, in combination with monoclonal antibody PM1, allowed us to
      characterize and quantify the proliferating and differentiating neuroepithelial
      cells. Interestingly, the fraction of total neuroepithelial cells that are
      stained with PM1 sharply decreases as retinal development proceeds, in
      correlation with the staining pattern in sections from matched stages. These data
      thus reveal that the pluripotent neural precursors in the chick retina already
      represent an intrinsically heterogeneous population, and that this population
      changes with development.

PMID- 8130928
TI  - Embryonic Purkinje cells grafted on the surface of the adult uninjured rat
      cerebellum migrate in the host parenchyma and induce sprouting of intact climbing
      fibres.
AB  - By grafting solid pieces of cerebellar anlage onto the surface of the adult rat
      cerebellum, we have investigated the problem of the interactions between
      embryonic and adult neurons in an intact brain. A few days after grafting,
      embryonic astrocytic processes crossed the graft--host interface and radiated
      into the recipient molecular layer. Several grafted Purkinje cells also migrated
      into the host brain along such processes as well as adult Bergmann glia. Adult
      climbing fibres, labelled by means of Phaseolus vulgaris leucoagglutinin (PHA-L),
      sprouted new collateral branches which terminated on embryonic Purkinje cells at
      both extra- and intraparenchymal levels. No sign of activation of host astroglia
      or microglia was evident in the host cerebellum in relation to these processes.
      Embryonic Purkinje cells which migrated into the host cerebellum developed an
      adult-like morphology. Intraparenchymal grafts of neocortical embryonic tissue
      induced conspicuous growth of host olivary axons, characterized by a pattern
      which was different from that observed following cerebellar grafts. By contrast,
      when neocortical tissue was placed onto the surface of the recipient cerebellum,
      graft--host interactions were limited and climbing fibre sprouting was rarely
      seen. These results show that (i) supernumerary Purkinje cells can penetrate and
      settle in the adult intact cerebellar cortex, (ii) adult climbing fibres are able
      to innervate these new targets in the absence of any injury or activation of non
      neuronal cells of the adult brain, and (iii) in the absence of damage to the
      adult brain, the plasticity of adult olivary axons is specifically elicited and
      controlled by embryonic Purkinje cells.

PMID- 8130929
TI  - A PET study of somatosensory discrimination in man. microgeometry versus
      macrogeometry.
AB  - The regional cerebral blood flow (rCBF) was measured with 15O-butanol and
      positron emission tomography (PET) in 10 healthy subjects in order to compare
      cerebral activation involved in the somatosensory discrimination of
      microgeometric features with cerebral activation associated with the
      discrimination of macrogeometric features. Subjects performed two-alternative
      forced choice (2-AFC) discriminations of pairs of stimuli from a series of
      quantified standardized stimuli that differed in roughness (microgeometry), and a
      separate 2-AFC task of smooth tactile stimuli that differed in length
      (macrogeometry). Results are presented from three conditions: (1) a roughness
      discrimination task; (2) a length discrimination task; and (3) a control trial in
      which subjects were required to reproduce similar exploratory finger movements
      only, but without a specific stimulus to feel. Mean subtraction images were
      computed using the computerized adjustable brain atlas of Greitz et al. (1991, J.
      Comput. Assisted Tomogr., 15, 26-38) and areas of significant blood flow change
      were identified. Both the roughness and the length discrimination tasks activated
      overlapping cortical fields contralaterally in the anterior and posterior lip of
      the postcentral sulcus. However, in the length discrimination, activation of the
      posterior lip of the postcentral sulcus extended deeper into the sulcus and there
      was also a separate additional area of activation in the anterior part of the
      precentral gyrus. Furthermore, the length discrimination task activated fields in
      the overt part of the supramarginal gyrus bilaterally as well as fields in the
      angular gyrus bilaterally. Thus roughness discrimination uses only a subset of
      the cortical regions that are needed for the recovery of length information,
      which requires more extensive somatosensory processing. This finding may be
      partly explained in that length perception needs both edge detection of the
      stimuli used, as well as integrated information of surface length and velocity,
      which is not necessary for roughness perception. Specific differences in the
      acquisition of necessary tactile information between the two discrimination tasks
      was reflected in different sampling strategies.

PMID- 8130930
TI  - Auditory localization behaviour in visually deprived cats.
AB  - The ability to localize sounds in azimuth was tested in five cats that had been
      binocularly deprived of vision from birth for several months and in three normal
      age-matched controls. Brief tone bursts were presented in an eight-choice
      apparatus along 360 degrees of the azimuthal plane at constant elevation. Using
      positive reinforcement techniques, the cats were trained to walk from the centre
      of the 3 m diameter circular enclosure to the hidden loudspeakers. The
      distribution of sound localization error from 55 trials per cat at each speaker
      position was measured, and its standard deviation was used to assess the
      precision of sound localization. All cats localized tones straight ahead of them
      most precisely; performance at lateral and rear positions was gradually less
      precise. When the sound localization ability of normal and binocularly deprived
      cats was compared across speakers, a significantly enhanced precision was found
      for binocularly deprived cats overall (P < 0.002; two-way analysis of variance).
      An improvement was found at each individual speaker position, but it was greatest
      at lateral and rear positions. In two sets of control experiments normal cats
      were retested (i) in the dark with the aid of an infrared camera and (ii) after 3
      months of binocular lid suture. Normal cats in the dark did not show any
      differences in their sound localization behaviour. Late-deprived cats showed a
      tendency for better performance, which fell short of statistical significance.
      Our results in visually deprived cats agree well with some reports on the sound
      localization ability of blind humans, but disagree with others. Our data provide
      support for a hypothesis of compensatory plasticity, in which sensory functions
      get sharpened with the loss of another modality. They seem to rule out the
      necessity for vision to play a role in the postnatal calibration of auditory
      space.

PMID- 8130931
TI  - Purinergic modulation of the evoked release of [3H]acetylcholine from the
      hippocampus and cerebral cortex of the rat: role of the ectonucleotidases.
AB  - Modulation by exogenous and endogenous adenine nucleotides and adenosine of
      [3H]acetylcholine release evoked by veratridine (10 microM) was compared in
      synaptosomal fractions from the hippocampus and the cerebral cortex of the rat.
      In both brain areas, exogenously added ATP or adenosine (10-100 microM) inhibited
      the evoked tritium release. In the hippocampus, ATP gamma S, an ATP analogue more
      resistant to catabolism than ATP, was virtually devoid of effect on tritium
      release, and the effect of ATP was prevented by the ecto-5'-nucleotidase
      inhibitor alpha,beta-methylene ADP (100 microM), by adenosine deaminase (2 U/ml)
      and by the A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine
      (DPCPX, 20 nM). In contrast, in the cerebral cortex, the effect of ATP on tritium
      release was not prevented by either alpha,beta-methylene ADP (100 microM) or
      adenosine deaminase (2 U/ml), and several ATP analogues (30 microM) inhibited
      release. The order of intensity of the inhibitory effects of the ATP analogues
      was: ATP gamma S > ATP > beta,gamma-imido ATP > beta,gamma-methylene ATP >> 2
      methyl-S-ATP, alpha,beta-methylene ATP. The effect of ATP gamma S in the cerebral
      cortex was prevented by DPCPX (20 nM) and was not affected by the P2 purinoceptor
      antagonist suramin (100 microM). In the hippocampus, alpha,beta-methylene ADP
      (100 microM) increased the evoked release of tritium, and adenosine deaminase (2
      U/ml) produced an even greater increase; when adenosine deaminase was added in
      the presence of alpha,beta-methylene ADP, adenosine deaminase still increased the
      evoked release of tritium. In the cerebral cortex, DPCPX (20 nM) and adenosine
      deaminase (2 U/ml) increased the evoked tritium release by a similar magnitude,
      but the effect of adenosine deaminase was smaller than in the hippocampus. It is
      concluded that in the cerebral cortex ATP as such presynaptically inhibits
      acetylcholine release, whereas in the hippocampus the role of adenine nucleotides
      is as a source of endogenous extracellular adenosine that tonically inhibits
      acetylcholine release. The results also show that besides formation of adenosine
      from adenine nucleotides, released adenosine as such contributes in nearly equal
      amounts to the pool of endogenous adenosine that presynaptically inhibits
      acetylcholine release in the hippocampus.

PMID- 8130932
TI  - Effect of peripheral axotomy on expression of neuropeptide Y receptor mRNA in rat
      lumbar dorsal root ganglia.
AB  - Using in situ hybridization, the expression of the mRNA for a neuropeptide Y
      (NPY) receptor, was studied in lumbar (L) 4 and 5 dorsal root ganglia (DRGs) of
      normal rats and at various intervals after unilateral sciatic nerve transection.
      Twenty percent of all normal DRG neurons were NPY receptor mRNA-positive, and the
      majority of these neurons were of the small type, with only a few labelled medium
      sized and large neurons. In L5 normal ganglia NPY receptor mRNA colocalized with
      substance P, calcitonin gene-related peptide and galanin mRNAs in small neurons,
      but not in medium-sized or large neurons containing these peptides. NPY receptor
      mRNA was not observed in somatostatin or nitric oxide synthase mRNA-positive
      neurons. Sciatic nerve transection induced a marked decrease in NPY receptor mRNA
      levels. However, in parallel there was a transient increase in the number of NPY
      receptor mRNA-positive small neuron profiles, but the intensity of labelling was
      mostly very low, although a few strongly labelled, small neuron profiles were
      also encountered. In addition, axotomy caused a marked increase in the number of
      NPY receptor mRNA-positive large neuron profiles in the ipsilateral DRGs, and
      they constituted 15-20% of counted DRG neuron profiles and 45-65% of counted
      large neuron profiles, 7-28 days after axotomy. In L5 DRGs, ipsilateral to the
      axotomy, NPY receptor mRNA colocalized with NPY mRNA in many large and some
      medium-sized neuron profiles, with galanin mRNA in some small, medium-sized and
      large neuron profiles and with vasoactive intestinal polypeptide mRNA in some
      small and medium-sized neuron profiles and a few large profiles. Occasionally,
      NPY receptor mRNA was observed in nitric oxide synthase mRNA-positive small
      neurons. In the dorsal horn, NPY receptor mRNA-positive small neurons were
      concentrated in lamina II at L4 and L5 levels, and were scattered in deeper
      laminae. No marked changes were observed ipsilateral to the axotomy. No NPY
      receptor mRNA-positive cells were found in the normal rat gracile nucleus, or in
      this nucleus after axotomy. These results show that a NPY receptor may be a
      prejunctional receptor in primary afferent neurons and play a role in the
      modulation of somatosensory information, both in normal and lesioned primary
      afferent DRG cells. However, axotomy induced a distinct shift in NPY receptor
      mRNA expression from small to large neurons, indicating that sensitivity to NPY
      is switched from one modality to another.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8130933
TI  - Differential localization and pH dependency of phosphoinositide 1,4,5-IP3,
      1,3,4,5-IP4 and IP6 receptors in rat and human brains.
AB  - It is well established that the inositol lipids mediate signal transduction in
      several cellular populations. Many neurotransmitters, hormones and growth factors
      act at plasma membrane receptors to induce the hydrolysis of
      phosphatidylinositols and hence the generation of various inositol phosphates
      (IP). The best known member of this family is 1,4,5-IP3, which is associated with
      the release of Ca2+ from intracellular pools. It has also been proposed that two
      others inositides, 1,3,4,5-IP4 and IP6, may be involved in Ca2+ homeostasis. In
      order to study the possible relevance of these various inositides in neuronal
      tissues, we have localized the respective receptors in rat and human brain under
      both acidic and basic pH conditions. In the hippocampal formation, [3H]1,3,4,5
      IP4 binding sites are concentrated in the hilus and the molecular layer while a
      clearly different pattern of distribution is seen for [3H]1,4,5-IP3, its highest
      concentration of labelling being concentrated in the oriens and radiatum laminae.
      This contrasting profile of distribution is also observed in other brain areas
      such as the caudate-putamen, the septo-hippocampal area, and the molecular and
      granular layers of the cerebellum. Moreover, while highest amounts of specific
      [3H]1,4,5-IP3 binding are obtained at pH 8.5, the opposite is found for
      [3H]1,3,4,5-IP4, with high binding levels seen under acidic conditions. [3H]IP6
      binding sites are broadly distributed with specific labelling concentrated in
      areas enriched with neuronal perikarya such as the granular cell layer of the
      dentate gyrus, the pyramidal cell layers of the hippocampus and the granular cell
      layer of the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130934
TI  - Early postnatal changes in the somatodendritic morphology of ankle flexor
      motoneurons in the rat.
AB  - The development of locomotor function in the rat spans the first 3 postnatal
      weeks. We have studied morphological features of the soma and dendrites of
      motoneurons innervating the physiological flexor muscles of the ankle, tibialis
      anterior and extensor digitorum longus, by intracellular injection in vitro
      between the first and ninth postnatal days. We obtained serial optical sections
      of 96 adequately filled motoneurons in whole-mounted hemisected spinal cords by
      confocal microscopy, projected them onto a single plane and analysed them
      morphometrically. On the day after birth, the somatodendritic surfaces of most
      such motoneurons were covered in growth-associated spiny, thorny or hair-like
      appendages. These had disappeared from the soma by the fourth postnatal day and
      from most proximal dendrites by day 7, but were still common distally on day 9.
      During this period there was little or no net growth of either the soma (which
      was still much smaller than in the adult) or the dendritic tree. A dorsal
      dendritic bias was present and 'sprays' of long, loosely bundled dorsal dendrites
      were often seen. The mean number of primary dendrites remained constant at about
      eight, and their combined diameter was already significantly correlated with mean
      soma diameter, as in the adult cat. Thus, the critical neonatal period during
      which these ankle flexor motoneurons are known to change their
      electrophysiological properties and to be particularly sensitive to interference
      with neuromuscular interaction is characterized by major changes in the neuronal
      surface, presumably linked to synaptogenesis.

PMID- 8130935
TI  - Axotomy-induced changes in Ca2+ homeostasis in rat sympathetic ganglion cells.
AB  - Some of the marked biochemical and electrophysiological changes provoked by
      section of the axon in mature neurons suggest that the intracellular calcium
      concentration ([Ca2+]i) may be increased. We have measured the [Ca2+]i using the
      fluorescent indicator Indo-1 microinjected into rat superior cervical ganglion
      neurons. No differences in resting [Ca2+]i levels were found between control
      neurons and cells which had been axotomized 7-10 days before. However, the rise
      in [Ca2+]i evoked by orthodromic or antidromic stimulation and the recovery after
      the stimulating train were considerably slower in axotomized neurons than in
      control cells. We also found that the number of calbindin-D28k-immunopositive
      cells in the ganglion increases after axotomy, which could be related to the
      observed differences in calcium homeostasis.

PMID- 8130936
TI  - Localization of oxytocin binding sites in the thoracic and upper lumbar spinal
      cord of the adult and postnatal rat: a histoautoradiographic study.
AB  - Oxytocin binding sites were detected by autoradiography on films and emulsion
      coated sections in the spinal cord of adult and postnatal rats from C8 to L2,
      using a highly selective 125I-labelled oxytocin antagonist. Oxytocin binding
      sites were detected on all transverse sections in the dorsal horn, where
      labelling was scattered over laminae I and II. The autonomic areas, i.e. the
      intermediolateral cell column, the central grey (lamina X) and the nucleus
      intercalatus were labelled. Binding in the intermediolateral cell column was most
      frequently observed on sections from T9 to T11 in adult and T7 to T8 in postnatal
      rats. In this location, oxytocin binding sites were highly concentrated on cell
      bodies of putative sympathetic preganglionic neurons; however, not all of these
      cells were labelled. Diffuse labelling occurred on the dorsal part of the central
      grey, mainly between T8 and L2. Isolated labelled cells belonging to the nucleus
      intercalatus were scattered between the central canal and the intermediolateral
      cell column. In addition, oxytocin binding sites were found on some motoneurons
      of the lateral group of T12-T13, but only in postnatal rats. The distribution of
      oxytocin binding sites in the rat spinal cord coincides with that of the oxytocin
      innervation and strongly suggests a modulatory role of this peptide in sensory
      and autonomic functions.

PMID- 8130937
TI  - Cholecystectomy and colorectal cancer in China.
AB  - Colorectal cancer is a major public health problem in China: 79,800 new cases are
      estimated to occur each year, which ranks it among the five most common tumours
      in China. Although the association between cholecystectomy and colorectal cancer
      has been studied elsewhere, few studies have been conducted in the Chinese
      population, characterized by a lower fat intake, and low colorectal cancer
      incidence. We conducted this hospital-based case-control study to explore this
      association. The study included a total of 503 incident cases with pathologically
      diagnosed colorectal cancer in Drum Tower Hospital at Nanjing in China from 1965
      to 1986, and 2188 healthy controls who had annual routine physical examinations
      at the same hospital. Diagnosis of cholelithiasis was confirmed by
      ultrasonography or X-ray cholecystography, and the information on cholecystectomy
      was obtained by checking medical charts for both cases and controls. The
      prevalence of cholelithiases was 5.8% for cases and 6.1% for controls (P > 0.05).
      Eight cases (1.6%) and 18 controls (0.8%) had a history of previous
      cholecystectomy. The period between cases' cholecystectomy and diagnosis of
      colorectal cancer ranged from 2.5 to 23 years, and the mean interval was 8.9
      years. The crude odds ratio for patients having previous cholecystectomy is 1.95
      (95% CI: 0.84-4.51) compared with controls. The odds ratio for female patients
      with previous cholecystectomy was 2.79 (95% CI: 1.03-7.59). When subsites were
      analysed, a significant association between right colon cancer and
      cholecystectomy was noted: the odds ratio was 6.2 (95% CI: 2.24-16.9), and that
      for females was even higher 8.61 (95% CI: 2.44-3.04) with statistical
      significance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130938
TI  - p53 overexpression as a marker of malignancy in gastric biopsies.
AB  - Inactivation of the p53 tumour-suppressor gene is the commonest genetic
      abnormality in human cancers. This results in a conformational change in the p53
      protein, and a consequent prolongation in its half-life; thereby permitting the
      identification of p53 immunoreactivity in malignant cells. Such reactivity is
      observed in up to 57% of gastric carcinomas, and is a proven indicator of poor
      prognosis. We have investigated the use of p53 immunohistochemistry in the
      diagnosis of malignancy in pre-operative gastric biopsy specimens. Using a three
      stage immunoperoxidase technique, p53 expression was examined in 117 gastric
      biopsies obtained during flexible upper gastrointestinal endoscopy: 80 of these
      biopsies were from known gastric carcinomas, 20 from benign gastric disorders and
      17 from normal gastric mucosa. Of the gastric cancers 40% (n = 32) exhibited
      overexpression of p53. No reactivity was observed in any of the biopsies of
      gastric ulcers, polyps or normal mucosa. The expression of p53 by gastric
      carcinomas improved the diagnostic accuracy of conventional histopathology from
      86% to 92.5%; with 5% of biopsies incorrectly diagnosed and 2.5% of an equivocal
      appearance. These results demonstrate that the detection of p53 is a highly
      specific marker of gastric malignancy, and that such a technique can easily be
      performed on biopsies obtained at endoscopy.

PMID- 8130939
TI  - A 50-year experience of male breast cancer: is outcome changing?
AB  - During the period 1933-1983, 124 men (median age 62.5 years, range 33-86 years)
      were treated for breast carcinoma. Median length of follow-up was 6.7 years and
      was complete for 93% of patients. Presenting complaints were most frequently a
      mass (95%) or pain (31%) while physical examination revealed the tumour to be
      central in 95% of patients with nipple or skin retraction in 36% and associated
      gynaecomastia in 12%. Twenty-seven per cent of the patients had a positive family
      history of breast cancer, 6% noted previous breast trauma and 7% had prior chest
      wall irradiation. Mean tumour size was 2.5 cm, and the pathological stage was 0
      in 3%, I in 17%, II in 22%, III in 35%, IV in 11%, and unknown in 12%. Ninety
      four per cent were ductal carcinoma. Histological grading of tumours was 2% grade
      1, 10% grade 2, 33% grade 3 and 48% grade 4. Ninety-two per cent of patients
      underwent mastectomy (41% radical, 39% modified radical and 12% simple), while
      adjuvant irradiation was used in 44% and chemotherapy in 9%. Median disease-free
      patient survival was 5 years (36% of patients developed tumour recurrence).
      Median overall patient survival was 6.3 years (57% at 5 years and 31% at 10
      years). Tumour size (P < 0.05), pathological stage (P < 0.04), and tumour grade
      (P = 0.007) were adverse factors for recurrence, while pathological stage (P <
      0.02), tumour size (P < 0.03), pain (P < 0.05) and age (P < 0.02) were associated
      with a decreased survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130940
TI  - Surgical resection and radiolocalization of the sentinel lymph node in breast
      cancer using a gamma probe.
AB  - We have recently reported on a technique of gamma probe localization of
      radiolabelled lymph nodes to identify the sentinel node in malignant melanoma. In
      order to determine whether this technique is applicable to assist in staging
      breast cancer, a pilot study was begun to address two questions: (i) can the
      sentinel lymph node draining a breast cancer be identified for selective
      resection; and (ii) is the sentinel lymph node predictive of the status of the
      entire axillary lymph nodes? One to four hours prior to axillary lymph node
      dissection, 22 consecutive patients had approximately 0.4 mCi of technetium
      sulfur colloid in 0.5 ml saline injected around the perimeter of the breast
      lesion. A hand-held gamma counter was used at surgery to locate the lymph node(s)
      receiving drainage from the breast. A sentinel lymph node was identified in 18 of
      22 patients. Of these 18 patients, the sentinel lymph node was positive in seven
      of seven patients, with pathologically verified metastatic breast cancer to at
      least one lymph node. In three out of seven patients, the sentinel lymph node was
      the only lymph node with metastatic cancer. In this pilot study of breast cancer
      patients, we conclude that: (i) radiolocalization and selective resection of
      sentinel lymph nodes is possible; and (ii) the sentinel lymph node appears to
      predict correctly the status of the remaining axilla. These data justify a larger
      clinical trial to verify the value of this technique.

PMID- 8130941
TI  - Nucleolar organizer regions are independently associated with a shortened
      survival in patients with non-small cell lung cancer.
AB  - We examined nucleolar organizer regions (Ag-NOR) in 102 patients with non-small
      cell lung cancer (NSCLC). Ag-NOR counts were generally higher in tumours from
      more advanced stages, or in poorly differentiated adenocarcinomas. Six potential
      prognostic indicators included sex, age, year of operation, histology, stage and
      Ag-NOR count. Stage and Ag-NOR counts had a significant prognostic value in the
      univariate analysis for 79 patients who died of their lung cancer. In the
      multivariate analysis, high Ag-NOR counts as well as disease stage were
      independently associated with a poor prognosis. Furthermore we divided patients
      into three groups according to their Ag-NOR counts and found that in patients
      with stage I and II disease higher Ag-NOR counts were associated with shortened
      survival. This trend did not continue in patients with stage III and IV disease.

PMID- 8130942
TI  - Regional procarbazine delivery reduces testicular toxicity.
AB  - Procarbazine has been implicated as a cause of infertility. Regionalization of
      drug delivery is a potential method to avoid this problem. We investigated the
      protective effect of testicular circulatory isolation (TCI) on gonadal toxicity
      during procarbazine administration in the Sprague-Dawley rat. Four groups (n =
      10/group) were used. Animals in group 1 received no treatment. Rats in groups 2
      and 3 were anaesthetized and received TCI of the left testis by clamping of the
      spermatic cord and gubernaculum immediately before a bolus of intravenous
      procarbazine (400 mg kg-1). The clamping was maintained for 15 min after
      procarbazine administration in group 2 and for 45 min in group 3. Rats in group 4
      received sham surgery immediately before procarbazine administration. On day 70,
      all rats were killed and necropsied. Testicular toxicity was evaluated
      qualitatively by histology and quantitatively by measurements of testicular
      weight, sperm head count, repopulation index, and epididymal index. The results
      indicated that 15 min of TCI did not mitigate testicular toxicity; 45 min of TCI
      provided moderate protection against procarbazine-induced testicular toxicity.

PMID- 8130943
TI  - Iodinated contrast agents in neuroradiology.
AB  - Intravascular iodinated contrast materials in neuroradiology commonly are used
      during CT scanning and cerebral arteriography. This article discusses their use
      and the selection of appropriate contrast media. Adverse contrast media
      reactions, with emphasis on neurotoxicity, and the use of low osmolar agents are
      discussed. In addition, this article discusses nephrotoxicity and the use of
      contrast material in special circumstances, including patients with
      hyperuricemia, multiple myeloma, sickle cell disease, thyroid disease,
      pheochromocytomas, and the use of contrast material in pediatric patients.

PMID- 8130944
TI  - Contrast enhancement in head and neck imaging.
AB  - Iodinated intravenous contrast material for CT of the extracranial head and neck
      is extremely useful in almost all clinical settings. Contrast material
      facilitates visualization of the carotid artery and jugular vein; helps delineate
      the full extent of neoplastic and inflammatory lesions, and in limited
      circumstances can suggest a precise diagnosis based on a particular pattern of
      enhancement. The role of gadolinium is not as clear. Gadolinium chelates are not
      routinely needed to opacify vessels, and with operator-dependent changes in pulse
      sequence parameters, contrast between a lesion and normal structures can be
      maximized. A number of studies, however, have shown that gadolinium can improve
      detection of perineural or intracranial spread of disease; confirm necrosis
      within lymph nodes, abscesses, or tumors; and more accurately show the full
      extent of disease into surrounding soft tissues. It is impossible to predict
      before imaging which patients will benefit from the addition of MR contrast
      agents, and for that reason enhanced images are often routinely acquired.

PMID- 8130945
TI  - Contrast-enhanced magnetic resonance imaging of the temporal bone.
AB  - The recent advances in MR imaging of the temporal bone brought about by the
      availability of intravenous contrast agents sensitive to the disruption of the
      blood-brain barrier have further expanded the role of MR imaging in the
      evaluation of this region. The main applications of contrast-enhanced MR imaging
      in the temporal bone are the evaluation of inflammatory and neoplastic processes
      of the labyrinth (in the general context of patients with sensorineural hearing
      loss or vertigo) peripheral seventh nerve palsies, and miscellaneous inflammatory
      and neoplastic conditions of the temporal bone itself.

PMID- 8130946
TI  - Contrast enhancement in meningeal and extra-axial disease.
AB  - Intravenous contrast agents have become an indispensable tool in the CT and MR
      evaluation of the CNS. With regard to extra-axial and meningeal processes, many
      lesions would be missed were it not for their tendency to enhance. Unfortunately,
      contrast enhancement for every patient undergoing neuroimaging may not be cost
      effective in the coming era of cost containment. Nonetheless, for patients with
      an underlying history of neoplastic or possible infectious disease and those
      whose symptoms are not explained by the noncontrast imaging findings, contrast
      enhanced imaging should be performed.

PMID- 8130947
TI  - Contrast-enhanced fat-suppression neuroimaging.
AB  - The commercially available fat-suppression methods currently do not produce
      quantitative fat suppression but in regions of minimal magnetic susceptibility
      effects and high magnetic and radiofrequency homogeneity are clinical tools that
      can increase confidence and specificity of diagnoses when applied appropriately.
      The advantages of these methods include a reduction in CSMA, improved tissue
      contrast allowing contrast-enhanced studies in fat-rich regions for greater
      sensitivity to pathology, and improved staging of lesions. These methods allow
      better use of the full dynamic range of the gray scale. Future improvements will
      include thin-section three-dimensional methods and susceptibility correction
      schemes, which will broaden the indications and increase the usefulness of fat
      suppression in clinical MR imaging.

PMID- 8130948
TI  - Magnetic resonance contrast agents in neuroimaging. New agents and applications.
AB  - Of the four gadolinium chelates in clinical use worldwide, only three are
      available in the United States: gadoteridol, gadodiamide, and gadopentetate
      dimeglumine. Although gadopentetate dimeglumine is still administered in many
      clinical practices, a consequence of being the first agent developed (1988) and
      until recently the only agent available, gadoteridol demonstrates a higher index
      of safety--at least on theoretical grounds. With linear chelates such as
      gadopentetate dimeglumine and gadodiamide, greater release of free gadolinium ion
      occurs in vivo owing to lower thermodynamic and kinetic stability. The concern
      with respect to demetallation and resultant increased chronic deposition of
      gadolinium ion in marrow and liver is greater with gadodiamide. Drug safety
      appears not to be an issue at high dose for gadoteridol, the only agent approved
      in this regards. The safety of the other chelates at high dose has yet to be
      established. The nonionic character of the two newer agents (gadoteridol and
      gadodiamide) is not of great importance in current clinical practice, in which
      most examinations are still performed with a dose of 0.1 mmol/kg given as a slow
      infusion. The non-ionic nature of the newer MR contrast agents may become
      clinically important in the future, with more common application of bolus
      injection and high dose. High contrast dose (0.3 mmol/kg) is advocated in routine
      MR clinical practice for the evaluation of intracranial metastatic disease. Only
      with prior evidence for multiple metastases and in patients for whom the
      detection of additional lesions would not influence therapy can the use of
      standard dose (0.1 mmol/kg) be justified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130949
TI  - Improved detection of gadolinium enhancement using magnetization transfer
      imaging.
AB  - Magnetization transfer (MT) imaging is a new MR imaging technique in which off
      resonance radiofrequency pulses are used to selectively saturate protons in
      macromolecules. This saturation effect is transferred subsequently (by dipolar
      and chemical exchange interactions) to protons in free water, thereby altering
      tissue relaxation times and modulating image contrast. Gadolinium enhancement is
      not significantly mediated by macromolecular interactions and is, therefore, not
      suppressed by MT pulses. The theory underlying the use of the MT technique is
      presented, with examples of its clinical usefulness in improving contrast
      enhancement for a variety of central nervous system diseases.

PMID- 8130950
TI  - Magnetic resonance contrast agents. Physical basis of relaxation.
AB  - Only through a combined understanding of contrast agent properties and
      fundamental contrast mechanisms, optimal administration and imaging techniques
      can be applied to contrast-enhanced MR imaging. It is impossible to cover all
      aspects of the physics of paramagnetic contrast agents in a short review. The
      basic theories of paramagnetic relaxation enhancement and susceptibility effects,
      presented in this article, are intended to help readers understand the behavior
      of existing contrast agents in clinical studies. Additional information about
      these phenomena can be found in other published reviews, and for a more in-depth
      coverage, the reader should turn to monographs and scientific papers that discuss
      the particular topics of interest.

PMID- 8130951
TI  - Magnetic resonance contrast agents for neuroimaging. Safety issues.
AB  - As physicians, we have an obligation to ensure the safety of our patients as well
      as to inform them of any potential risks associated with diagnostic procedures.
      The overall safety profile of the magnetopharmaceuticals with current FDA
      approval is good with regard to acute toxicity. For gadopentetate dimeglumine,
      toxicity. For gadopentetate dimeglumine, the agent with the greatest clinical
      experience, the overriding majority of adverse events consists of transient and
      relatively minor symptoms and reactions. Clinical trials of the newer agents
      reflect a similar experience but on a much smaller scale. Continued post
      marketing surveillance programs should provide more information in the near
      future. Severe adverse reactions do occur after the administration of
      magnetopharmaceuticals. These often idiosyncratic and anaphylactoid reactions may
      cause permanent injury or death. In the two reported cases to date, the patients
      had a history of reactive airway disease. The incidence of severe reactions is
      estimated at 1 in 350,000 to 450,000 for gadopentetate dimeglumine. The rate is
      considerably lower than that for iodinated contrast agents, both ionic and
      nonionic. Magnetopharmaceuticals should be considered safe but not innocuous. The
      small risk must be weighed against the additional diagnostic information that is
      obtained with magnetopharmaceuticals. Radiologists should be aware of potential
      complications and have on site equipment and skilled personnel for management
      should an adverse event occur. The benefits to the patient of reduced morbidity
      and mortality from improved diagnosis with magnetopharmaceuticals will ensure
      continued use of current agents as well as development of additional agents.

PMID- 8130952
TI  - Utility of magnetic resonance contrast agents in routine cranial imaging. Case
      study of an evaluative method.
AB  - Scientific studies that document the utility and value of MR imaging in routine
      clinical practice must differ from double-blind, randomized clinical trials. The
      case study in this article represents an effort to create pragmatic methods for
      these clinical environments. An independent, judicial panel reviewed blinded
      readings of unenhanced and enhanced MR images. This panel determined that Gd-DTPA
      enhancement improved the readings that were close enough for clinical purposes-
      called Diagnostic Merit. More importantly, clinical care was not disrupted, and
      statistically significant benefits were shown in routine practice. Such studies
      could lead to earlier reimbursement for useful imaging technologies.

PMID- 8130953
TI  - Contrast enhancement in primary tumors of the brain and spinal cord.
AB  - The patterns of contrast enhancement by CT and MR imaging for most intramedullary
      primary tumors of the brain and spinal cord are discussed. Contrast
      administration allows for the separation of tumor from normal neighboring tissues
      in most cases. Although most of the published data refer to contrast-enhanced CT
      scanning, gadolinium-enhanced MR imaging has become the modality of choice in the
      evaluation of primary central nervous system tumors.

PMID- 8130954
TI  - Gadolinium contrast dose in the evaluation of central nervous system tumors.
AB  - Many factors affect the ability to detect a CNS lesion. There is no single
      contrast dose that is optimal for all diseases. By understanding these factors
      that may affect lesion detection, the appropriate dose for specific pathologic
      processes may be determined.

PMID- 8130955
TI  - Magnetic resonance contrast enhancement in cerebral infarction.
AB  - Contrast enhancement may aid significantly in the diagnosis, dating, and grading
      of cerebral infarctions. On MR imaging, four patterns of contrast enhancement may
      be distinguished: intravascular, meningeal, transitional, and parenchymal. Each
      pattern has a different appearance, time course, and clinical significance. The
      anatomic and physiologic mechanisms that give rise to these distinct types of
      contrast enhancement in cerebral infarction are discussed.

PMID- 8130956
TI  - Contrast agents in neuroimaging.
AB  - Until there is total elimination of adverse reactions and side effects with
      contrast agents, there will continue to be a need for improvement. The ideal
      contrast agent should be efficacious, safe, water soluble, with chemical and heat
      stability, biologically inert, with low viscosity, with osmolality the same as
      human serum, with selective excretion by the kidneys, and inexpensive.

PMID- 8130957
TI  - Throwing injuries of the shoulder.
AB  - A review of the mechanism of throwing is presented and split into the different
      phases. The presentation and history is often more important than the clinical
      signs which may only be present after repetitive throwing activity. The
      pathological relationship between instability and impingement is discussed.
      Arthroscopy has been found to be extremely helpful in extending knowledge of
      pathological anatomy as well as defining diagnosis and aiding treatment.

PMID- 8130958
TI  - Maximal shuttle running over 40 m as a measure of anaerobic performance.
AB  - Over the last decade increasing interest has been shown in the measurement of
      anaerobic power and capacity in athletic men. These physiological characteristics
      have been determined predominantly using cycle ergometry and treadmill sprinting.
      The purpose of the present study was to examine the relationship between 40-m
      maximal shuttle run times and performance indices obtained during treadmill
      sprinting and cycle ergometry. Moderate correlations were found between 10-m
      split times (the time taken to cover the initial 10 m of the shuttle course) and
      treadmill peak power outputs (r = -0.67; P < 0.05). Similar relationships were
      also found between the fastest 40-m time and mean power outputs generated on both
      the treadmill and cycle ergometer (r = -0.67; P < 0.05) and (r = -0.75; P < 0.05)
      respectively. The correlations remained unchanged when the values were adjusted
      for body weight (W kg-1). The results of the present study suggest that maximal
      40-m shuttle running ability may reflect anaerobic indices of power and capacity,
      determined using standard laboratory procedures.

PMID- 8130959
TI  - Assessment of tennis elbow using the Marcy Wedge-Pro.
AB  - The Marcy Wedge-Pro (MWP), a device used in training by tennis players, was
      employed in the assessment of tennis elbow. The MWP was used to measure the
      ability of patients to perform wrist extension exercises, since pain resulting
      from this specific activity is a prominent symptom of the condition. The MWP
      results were compared with clinical measures and found to identify accurately
      patients who responded to treatment (P < 0.05). This study illustrates the
      potential of the MWP to assess tennis elbow quantitatively.

PMID- 8130960
TI  - Morphological and physiological studies on Indian national kabaddi players.
AB  - Twenty-five national kabaddi players (Asiad gold medalists 1990), mean age 27.91
      years, who attended a national camp at the Sports Authority of India, Bangalore
      before the Beijing Asian Games in 1990, were investigated for their physical
      characteristics, body fat, lean body mass (LBM) and somatotype. The physiological
      characteristics assessed included back strength, maximum oxygen uptake capacity
      and anaerobic capacity (oxygen debt) and related cardiorespiratory parameters
      (oxygen pulse, breathing equivalent, maximum pulmonary ventilation, maximum heart
      rate). Body fat was calculated from skinfold thicknesses taken at four different
      sites, using Harpenden skinfold calipers. An exercise test (graded protocol) was
      performed on a bicycle ergometer (ER-900) using a computerized EOS Sprint
      (Jaeger, West Germany). The mean(s.d.) percentage body fat (17.56(3.48)) of
      kabaddi players was found to be higher than normal sedentary people. Their
      physique was found to be endomorphic mesomorph (3.8-5.2-1.7). Mean(s.d.) back
      strength, maximum oxygen uptake capacity (VO2max) and oxygen debt were found to
      be 162.6(18.08) kg, 42.6(4.91) ml kg-1 min-1 and 5.02(1.29) litre respectively.
      Physical characteristics, percentage body fat, somatotype, maximum oxygen uptake
      capacity and anaerobic capacity (oxygen debt) and other cardiorespiratory
      parameters were compared with other national counterparts. Present data are
      comparable with data for judo, wrestling and weightlifting. Since no such study
      has been conducted on international counterparts, these data could not be
      compared. These data may act as a guideline in the selection of future kabaddi
      players and to attain the physiological status comparable to the present gold
      medalists.

PMID- 8130961
TI  - Flexibility and posture assessment in relation to hamstring injury.
AB  - Posture and flexibility were assessed in 34 athletes. Subjects were divided into
      two groups: (1) a noninjured group that did not have a history of hamstring
      strain injury within the previous 12 months; (2) an injured group that had a
      history of hamstring strain within the previous 12 months. Ten postural
      components were assessed: head erectness; shoulder symmetry; spinal curvature;
      hip symmetry; foot and ankle alignment; knee hyperextension; upper back
      roundness; trunk erectness; abdomen protrusion; and lumbar lordosis. Hamstring
      flexibility was assessed in both legs. Results indicated no difference (P > 0.05)
      in flexibility between groups (mean(s.d.) of both legs was: noninjured =
      77.1(9.3) degrees, injured = 77.8(9.2) degrees. Also no difference (P > 0.05) was
      observed between the injured limb and the noninjured limb for injured subjects
      (injured limb = 78.1(11.1) degrees, noninjured limb = 77.5(8.1) degrees. A
      significant difference (P < 0.01) between groups occurred in low back posture
      (lumbar lordosis). No other difference occurred in the remaining nine posture
      components between groups. Intercorrelation coefficients among posture components
      indicated that at best only 53% of common variance existed between any two
      components (head and shoulder components: r = 0.73, P < 0.01). All other
      correlations indicated less than 40% common variance between components. The
      results of the study indicate that while differences in hamstring flexibility are
      not evident between injured and noninjured groups poorer low back posture was
      found in the injured group. Regular monitoring of posture in athletes is
      recommended.

PMID- 8130962
TI  - Plasma TSH, T3, T4 and cortisol responses to swimming at varying water
      temperatures.
AB  - The acute effect of 30-min swimming at a moderate speed, at three water
      temperatures (20, 26 and 32 degrees C) on plasma thyroid stimulating hormone
      (TSH), free thyroxine (F.T4), triiodothyronine (T3) and cortisol concentrations
      was studied in 15 elite male swimmers. Blood was sampled before and immediately
      after the events. The heart rate, which was continuously monitored during
      exercise, had the highest response at 32 degrees C and the lowest at 20 degrees
      C. Blood lactate concentrations were found to be similar after the three tests.
      Plasma TSH and F.T4 were found to be significantly increased (by 90.4% and 45.7%
      respectively) after swimming at 20 degrees C, decreased at 32 degrees C (by 22.3%
      and 10.1% respectively) and unchanged at 26 degrees C. Exercise at these three
      water temperatures did not significantly affect T3. Finally, plasma cortisol was
      found to be increased after swimming at 32 degrees C (by 82.8%) and 26 degrees C
      (by 46.9%), but decreased at 20 degrees C (by 6.1%).

PMID- 8130963
TI  - Ice hockey injuries: a 4-year prospective study of a Swedish elite ice hockey
      team.
AB  - In this prospective study, we have investigated the incidence of injuries of
      different severity, types of injury, and mechanisms of injury during ice hockey
      practice and games. One Swedish elite hockey team was closely observed during
      four seasons (1986-1990). There were 376 injuries, of which 148 resulted in
      absence from practice or games. The incidence of injury (injuries associated with
      later absence) during practice was 2.6 per 1000 player-practice hours and 74.1
      per 1000 player-game hours. Nuisance injuries (without any later absence) and
      minor injuries (absence < 1 week) constituted the vast majority (95.2%) and only
      4.8% (18 cases) were classified as moderate or major injuries (absence > 1 week).
      Of the injuries 85% were caused by trauma and 15% by overuse. Injuries were most
      often localized to the lower limb (37.8%) and head/face (31.4%). The commonest
      injuries were contusions, lacerations/wounds, strains and sprains. Most injuries
      resulted from stick or player contact (predominantly checking). The results are
      in close agreement with those of a previous investigation of another Swedish
      elite hockey team covering the years 1982-1985. It should be possible to reduce
      the number of injuries by stricter enforcement of the hockey rules, especially
      against stick violations, and a more widespread use of visors.

PMID- 8130965
TI  - Left-right asymmetry in two types of soccer kick.
AB  - The ability to kick with both feet is regarded as a desirable skill in high level
      soccer players; however, most players display a dominance of kicking ability on
      one side. This study investigated the characteristics of asymmetry in two types
      of soccer kick. A low drive and a chip kick from both the left and right foot of
      12 elite junior soccer players were analysed. Kick velocity, kick accuracy,
      position of the plant foot from the ball centre, and time from foot plant to ball
      contact were measured for each kick. Knee extension and flexion strength were
      also determined for each leg at 60 degree s-1, 180 degree s-1 and 240 degrees s-1
      on a Cybex II Isokinetic Dynamometer. A single factor repeated measures analysis
      of variance was applied to velocity, plant foot position and timing parameters to
      compare between sides and between shots. chi 2 analysis was used to compare
      accuracy between shots and between sides, and a paired Student's t test was used
      to compare strength parameters between sides. Pearson's product moment
      correlation analysis was used to examine the relationship between velocity and
      both leg strength and the time from foot plant to ball contact. Significance was
      set at P < or = 0.05. The results showed that this group had strength dominance
      at all speeds tested on the right side and better drive kick performance with
      their right leg as determined by mean(s.d.) velocity (79(6) versus 66(8) km h-1)
      and accuracy (66.6% versus 33.3%). There was no difference in these parameters
      between sides for chip kicks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8130964
TI  - The effects of the modified intermittent sequential pneumatic device (MISPD) on
      exercise performance following an exhaustive exercise bout.
AB  - The Lymphapress, a pneumatic sequential intermittent device is recognized as one
      of the most effective conservative treatments for lymphoedema, due to its
      effective 'milking mechanism'. This led us to hypothesize that accelerated
      removal of fatigue-causing metabolites by mechanical massage could improve an
      athlete's performance capacity. We conducted trials with 11 men who exercised at
      a constant workload, on a cycle ergometer, until exhaustion. During a 20-min
      recovery period a new modified pneumatic sequential intermittent device (the
      MISPD) was applied to the subjects' legs. The men then performed a second
      constant load exercise bout. Cardiorespiratory parameters were measured during
      exercise and blood was withdrawn during recovery for the determination of
      lactate, pyruvate, ammonia, bicarbonate and pH. No difference was found in the
      blood levels of the 'fatigue causing metabolites' during passive recovery (PR)
      and recovery with the MISPD (MR). However, the MISPD effected a 45% improvement
      in the subjects' ability to perform the subsequent exercise bout. The
      accumulation of fluid in the interstitial space after exercise and its
      disappearance after the use of the MISPD offers one possible explanation for
      these results, although psychological effects cannot be discounted.

PMID- 8130966
TI  - Sports causing most injuries in Hong Kong.
AB  - A prospective survey was carried out on 2293 patients attending the Sports Injury
      Clinic in the Prince of Wales Hospital between May 1984 and December 1990. A
      Sports Injury Report Form was completed for each patient. Subjects in this study
      represent a group of nonprofessional and non-elite athletes in a metropolitan
      area. Soccer, basketball, volleyball, long-distance running and cycling in
      descending order were the five most common sports causing injury. Different
      sports produced different injury patterns. In four of the five sports, the knee
      (27.27-50.47%) and the ankle (16.78-24.67%) were the commonest sites of injury.
      In cycling, the face (19.46%) was the commonest site of injury. There was a
      higher injury rate to the lower than the upper limb in soccer, basketball,
      volleyball and long-distance running, with a ratio of upper- to lower-limb injury
      ranging from 1:1.13 to 1:46.10. In cycling, upper limb injury was more frequent
      (upper- to lower-limb injury ratio was 1:0.53). Sprain was the commonest injury
      overall (44.60%). It was also the commonest injury condition in volleyball
      (55.15%), basketball (55.34%), soccer (51.41%) and long-distance running
      (39.33%). In cycling, abrasion (24.83%) was commonest.

PMID- 8130967
TI  - The 'S' Quattro--results of treatment in 11 cases of sports injury.
AB  - The 'S' Quattro is a dynamic external fixator which has been designed to treat
      displaced comminuted intraarticular fractures of the phalanges. This type of
      fracture is commonly the result of a sports injury. We present a follow-up study
      of 11 cases.

PMID- 8130968
TI  - Plasma lipid, lipoprotein and apolipoprotein profiles in Nigerian university
      athletes and non-athletes.
AB  - The fasting plasma lipid, lipoprotein and apolipoprotein profiles were determined
      in 14 healthy Nigerian male athletes and controls matched for sex and
      anthropometric parameters. The mean levels of total cholesterol (P < 0.05), low
      density lipoprotein (LDL) cholesterol, apolipoprotein (apo) AII and E were
      significantly lower (P < 0.01) in the athletes than in the controls. However,
      there were no statistically significant differences (P > 0.05) between the mean
      values of the plasma triglycerides, high-density lipoprotein (HDL), very low
      density lipoprotein (VLDL) cholesterol, apo AI, B, Lp(a), LpA1 and CIII:NonB
      respectively for the athletes and controls. A priori, the potential effect on
      cardiovascular disease (CVD) risk was also compared using three predictor ratios 
      total cholesterol: HDL cholesterol (TC:HDL), LDL cholesterol: HDL cholesterol
      and apo B:AI. The mean of the three ratios was lower in the athletes than in the
      controls; however, the differences were not statistically significant (P > 0.05).
      Based on our data, exercise appears to decrease the TC:HDL ratio in the athletes
      by lowering LDL-cholesterol, while the HDL-cholesterol is unaffected. We conclude
      that physical activity has salutary effects on the lipid, lipoprotein and
      apolipoprotein profiles of healthy Nigerian men.

PMID- 8130969
TI  - Stress fracture of the lateral process of the talus--a case report.
AB  - A diagnosis of stress fracture of the lateral process of the talus was made in a
      52-year-old tennis player with chronic lateral ankle pain. This uncommon
      condition should be considered in the differential diagnosis of chronic lateral
      ankle pain in an athlete, as delay in appropriate treatment may lead to
      considerable morbidity.

PMID- 8130970
TI  - Distal radial fracture in gymnastics.

PMID- 8130971
TI  - Angioplasty gives good results in critical lower limb ischaemia. A 5-year follow
      up in patients with known ankle pressure and diabetic status having
      femoropopliteal dilations.
AB  - 137 consecutive patients with known ankle pressures and diabetic status had
      attempted femoro-popliteal dilatation for lower limb ischaemia in an English
      provincial teaching hospital. All except one were followed until failure or death
      to assess survival and amputation rates. Non-diabetic patients with critical limb
      ischaemia had a 5 year survival rate of 62.2% (SE 17.1) compared to 50.5% (SE
      7.0) for claudicants, with no significant difference on logrank testing.
      Diabetics had a relative risk of amputation of 11.2 compared to nondiabetics.
      Patients with pre-treatment ankle pressures of 50 mm or less had a relative risk
      of amputation of 2.6 compared to those with higher resting pressures. It is
      concluded that angioplasty should be the treatment of first choice in critical
      lower limb ischaemia whenever it is technically possible. Including patients with
      rest pain in the critical ischaemia group does not significantly affect
      cumulative patency rates.

PMID- 8130972
TI  - Lung metastasectomy in patients with soft tissue sarcoma.
AB  - Metastases develop in 50-60% of patients with high grade soft tissue sarcomas
      despite primary treatment. Between 1970 and 1990, 189 patients with soft tissue
      sarcoma referred to the Royal Marsden Hospital Sarcoma Unit developed lung
      metastases as the sole first site of disseminated disease. 44 of these 189 cases
      have been treated by pulmonary metastasectomy. In an attempt to determine which
      patients benefit from this surgery the medical records, radiology and pathology
      of these cases have been reviewed. Both the overall 5 year survival (70% vs 19%)
      and the subsequent survival from the time lung metastases developed (52% vs 7.5%)
      of those selected for thoracotomy were better than in the 145 patients not
      undergoing surgery. On multivariate analysis, survival and control of lung
      disease following resection were not related to the number of metastases
      resected, completeness of excision, use of adjuvant chemotherapy or presence of
      bilateral disease. The most important factor was the use of lung resection itself
      as treatment, for which the risk of death was 0.2 compared with those not having
      metastasectomy. Age less than 40 years and primary tumour in a lower limb site
      were also factors associated with a reduced risk of death. Pulmonary
      metastasectomy should be considered in selected patients with soft tissue sarcoma
      after primary local cure. However, without collection of prospective data on all
      patients developing lung metastases or a randomized trial the true role of lung
      metatasectomy will never be clarified.

PMID- 8130973
TI  - Diagnostic pharmaco-scintigraphy with hepatic intra-arterial technetium-99m
      macroaggregated albumin in the determination of tumour to non-tumour uptake ratio
      in hepatocellular carcinoma.
AB  - Between October 1990 and March 1993, 124 patients who had hepatocellular
      carcinoma (HCC) underwent diagnostic pharmaco-scintigraphy with hepatic
      intraarterial technetium-99m macroaggregated albumin (TcMAA) to determine the
      tumourous to non-tumourous liver tissue uptake ratio (T/N ratio). There were 110
      males and 14 females. Ages ranged from 16 to 73 with a median of 55 years. The
      range of T/N ratio was 0.7 to 19.3 with a median of 3.8. 12 patients with
      inoperable HCC were subsequently selected by predetermined criteria to undergo
      treatment with hepatic intraarterial yttrium-90 microspheres and the T/N ratios
      in these patients were validated by beta probe dosimetry and liquid scintillation
      count of multiple liver biopsies. The T/N ratio determined by preoperative
      diagnostic TcMAA scan correlated well with intraoperative beta probe dosimetry,
      with coefficient of correlation r = 0.82. Preoperative TcMAA scan also correlated
      well with liquid scintillation count of biopsy specimens, with r = 0.96. We
      conclude that TcMAA scan can be used to determine the T/N ratio in patients with
      HCC, thus allowing better selection of patients with inoperable tumours for loco
      regional therapy.

PMID- 8130974
TI  - Intrapelvic two-dimensional time-of-flight magnetic resonance angiography in
      healthy and diseased subjects.
AB  - We evaluated the use of magnetic resonance angiography (MRA) based on two
      dimensional (2D) time-of-flight (TOF) technique in the pelvic vasculature. In the
      initial phase of this study, MRA was performed in 10 normal subjects for
      determination of the optimum imaging parameters. Systemically varied scan
      parameters included flip angle ranging from 20 degrees to 90 degrees by 10
      degrees increments and repetition time (TR) of 30, 40, and 50 ms. The optimum
      imaging parameters for intrapelvic MR angiography were found to be flip angle of
      90 degrees, pulse sequence of 30/4.9 (TR ms/TE ms). Using these imaging
      parameters, 70-100% of the second division branches of the internal iliac artery
      could be visualized in each subject. In the second phase of this study, we
      evaluated the use of MR angiography in patients with intrapelvic vascular disease
      by comparing its accuracy in evaluating the iliac arteries with that of
      conventional angiography. In patients with atheromatous disease, the MR
      angiographic determination was consistent with that of conventional angiography
      in 23 of 28 visualized arterial segments (82%). In eight lesions in patients with
      non-stenotic vascular disease or hypervascular pelvic tumours, all lesions were
      demonstrated clearly with MR angiography. 2D TOF technique with high flip angle
      excitation is suitable for the evaluation of main iliac branches and diseased
      vessels.

PMID- 8130975
TI  - Plain film diagnosis in intussusception.
AB  - In early childhood intussusception a characteristic gas pattern is often visible
      on plain radiographs which can be used for diagnosis. To test this hypothesis,
      radiographs of 163 children with intussusception, and as many controls, were
      reviewed. By using multivariable analysis, it appeared that five out of seven
      parameters (reduced amount of gas in the jejunum; lateralization of the ileum;
      indiscernible caecum; reduced amount of feces in the colon; and visibility of the
      intussusceptum) had discriminatory value. For each parameter a weighting (in
      points) was derived and the patients were classified: the higher the score the
      more likely that an intussusception was present. A sensitivity of 90% and a
      specificity of 90% were obtained.

PMID- 8130976
TI  - Multiparametric classification of muscle T1 and T2 relaxation times determined by
      magnetic resonance imaging. The effects of dynamic exercise in trained and
      untrained subjects.
AB  - Muscle relaxation times can now be measured accurately with magnetic resonance
      imaging (MRI), distinguishing working muscles from non-working muscles. A
      correlation between T2 increase and work intensity has been shown in healthy
      volunteers. The small amount of data on T1 relaxation times is contradictory. In
      addition, all the published studies have concerned short-duration exercise in
      subjects of unknown training level. The goals of this study were (i) to determine
      T1 and T2 variations in thigh muscles after long dynamic exercise, (ii) to
      analyse the effects of training and (iii) to determine the relationship between
      power output and relaxation times after exercise. Sedentary men, soccer players
      and tri-athletes performed submaximal dynamic exercise at a constant heart rate
      for 15 min. MRI was performed before and 5 min after the end of exercise. The
      results showed (i) that T1 increased in parallel to T2 in anterior thigh muscles
      and (ii) that multiple correspondence analysis and hierarchical ascending
      classification can discriminate three subjects classes according to power output,
      training level and relaxation times, which fitted well with our three groups of
      subjects.

PMID- 8130977
TI  - An investigation of spinal bone mineral density measured laterally: a normal
      range for UK women.
AB  - A UK normal range for 250 volunteers was established for bone mineral density
      (BMD) of the lumbar spine (L2-L4) measured laterally in the decubitus position.
      Two software defined regions of interest ("Body" and "Mid") within the vertebral
      body were analysed throughout. As expected, a negative correlation of BMD with
      age was found for Body (r = -0.55, p < 0.001) and Mid (r = -0.56, p < 0.001). The
      age related bone loss from young to old (20-80 years) was 40% in L3 (Body) and
      45% in L3 (Mid). In 22% of the cases only L3 could be measured owing to the
      influence of rib over L2 and interference of the iliac crest over L4. Age related
      normal ranges (+/- 2 standard deviations) for the three lumbar vertebra L2, L3,
      L4 for young normals (age 19-39 years) were found to be 0.54 to 1.02, 0.49 to
      1.05 and 0.5 to 1.14 g cm-2 respectively for the Body region and 0.49 to 0.97,
      0.45 to 1.01 and 0.45 to 1.13 g cm-2 respectively for the Mid region. These
      ranges can now be used as reference values for patients with suspected
      osteoporosis and possibly for future fracture prediction. The in vivo precision
      in 19 volunteers was found to be 4.2% and 5.6% on Body and Mid respectively. The
      short term (less than 1 week) in vitro precision was 3.1% and 2.7% respectively.
      From these data it appears that there is a greater measured age related drop in
      BMD in the vertebral body (measured laterally) than in the entire vertebra
      (measured anterior-posteriorly) indicating that the lateral measurement may prove
      to be more sensitive in predicting fracture. The precision of these results
      indicates that lateral measurements of the spine are not yet useful for
      monitoring individuals over short term periods and are less useful for studying
      the effects of drug treatment than the more traditional anterior-posterior
      measurement of the spine and femur.

PMID- 8130978
TI  - Comparison of a new dual characteristic film-screen system (insight) with a
      standard film-screen system for chest radiology.
AB  - A new dual image receptor screen-film combination has been developed by Kodak
      with the objective of improving mediastinal and retro-cardiac detail whilst
      retaining good contrast and detail in the lung fields. This system was compared
      with our standard chest system. The study population was 36 patients with
      sarcoidosis. A postero-anterior (PA) chest film using our standard system was
      followed by a PA chest film using the new system--both using high kVp technique.
      The pairs of radiographs were assessed for (1) presence or absence of
      lymphadenopathy; (2) visibility of anterior and posterior mediastinal and azygo
      esophageal lines; (3) visibility of vessels in the outer and inner thirds of the
      lungs and (4) visibility of infiltrates, if present. The new film-screen
      combination was judged to show the mediastinal structures better in almost all
      instances. However, our standard combination was preferred for lung detail
      visualization in most cases. No significant difference was found between the two
      systems in their ability to demonstrate lymphadenopathy. The results were almost
      unchanged when the observers were given the option to score the criteria as
      equally well demonstrated on both films as opposed to not having this option
      available. We feel the advantages of the Insight system do not compensate for the
      significant loss of parenchymal detail resulting from the use of this system.

PMID- 8130979
TI  - Image quality and patient dose for different screen-film combinations.
AB  - Comparisons of image quality and estimations of dose reductions were made for
      several new screen-film combinations including conventional and rare-earth
      systems under conditions similar to abdomen radiography. The evaluation was
      carried out using an ANSI type phantom and the TOR(CDR) image quality object
      developed by the University of Leeds. The parameters employed for the comparison
      were: entrance dose, high and low contrast threshold sensitivity and resolution.
      The advantages and limitations of the method are also discussed. Results show
      that images with high quality can be obtained with comparatively low patient
      doses, and that there are still wide differences in image quality for similar
      speed systems, depending on the manufacturer and on the chosen combination.

PMID- 8130980
TI  - A comparison of mammographic phantoms.
AB  - It is important to establish and maintain high standards of image quality in
      mammography in order to detect breast cancer at an early stage. A commonly used
      method of assessing image quality in mammography is to use test phantoms. This
      paper reports a comparison of seven mammographic phantoms. These are the
      Ackermann (DuPont, Stevenage), Barts (White and Tucker), CIRS XI (Computerized
      Imaging Reference Systems, USA), Leeds TOR(MAX) and Leeds TOR(MAM) (Faxil,
      Leeds), Newcastle, and RMI 152 (Gammex RMI, Nottingham). These phantoms were
      assessed on the detectability of the various details and bar patterns contained
      in each. Step wedges and simulated anatomical features were not assessed. The
      effect on phantom images of changes in contrast, caused by changing tube
      potential from 25 kV to 35 kV, and of changes in resolution, caused by different
      focal spot sizes and by different magnifications, were investigated. It was
      deduced from the results of this study that there was no single phantom which was
      clearly superior to all the others. The three phantoms which had the greatest
      sensitivity to changes in imaging parameters were the Leeds TOR(MAM), the
      Newcastle and the Ackermann (DuPont) phantoms.

PMID- 8130981
TI  - Afterloading radiotherapy for local persistence of nasopharyngeal carcinoma.
AB  - 71 patients suffering from local persistence of nasopharyngeal carcinoma after
      primary external radiotherapy were treated by afterloading intracavitary 192Ir.
      66 (93.0%) had a complete response as evidenced by fibreoptic nasopharyngoscope
      examination and biopsy 4 weeks after the treatment. Significant prognosticators
      were studied by both monovariate and multivariate analysis. The early overall
      clinical stage at first presentation predicted a favourable survival. Local
      tumour control was adversely affected by advanced T-stage at first presentation,
      and by using a single 192Ir source, unilaterally applied to treat only one side
      of the nasopharynx. The intracavitary treatment was tolerated well and treatment
      complications were confined to the nasopharynx: chronic radiation ulceration
      (five patients) and diffuse telangiectasia (three patients).

PMID- 8130982
TI  - Craniospinal axis irradiation: an improved electron technique for irradiation of
      the spinal axis.
AB  - In this work we review the dosimetric features of craniospinal axis irradiation
      in the areas of matching cranial and spinal fields, with reference to the normal
      structures within the spinal field. The implications of the use of photon or
      electron modalities for the spinal port were evaluated. A novel method of
      matching the cranial photon and the spinal electron fields involving a computer
      aided junction design is presented. The technique involves moving the photon beam
      in three steps to degrade its penumbra to match that of the electron field.
      Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose
      volume histogram study for an illustrative paediatric case were used to compare
      the dose to normal structures within the spinal field. Our results show that the
      use of electrons for the spinal field leads to better sparing of deep seated
      normal structures. In the case of bone marrow, the use of a customized bolus for
      the spinal field results in an improved dose distribution, making electrons
      potentially superior to photons for radiobiological reasons.

PMID- 8130983
TI  - Calibration of low activity caesium tubes and needles traceable to the therapy
      level standard.
AB  - A technique for deriving the reference air kerma rate for low activity
      brachytherapy sources that is traceable to the therapy level standard at the
      National Physical Laboratory is presented. Correction factors have been generated
      to account for the finite source and detector size. The air kerma rate
      calibration of the secondary standard for caesium quality has been derived by
      polynomial curve fitting. The reference air kerma rates for several caesium tubes
      and needles have been determined and the results compared with the manufacturers'
      source test reports. For all the source types used the agreement between methods
      was within 2%.

PMID- 8130984
TI  - Technical note: measurement of computed tomography scanner slice widths.
AB  - The slice width of a computed tomography scanner can be considered as the full
      width at half maximum (FWHM) of the slice dose profile. A method is described
      which uses dental film to image the slice and allows the FWHM of the dose profile
      to be determine directly from the digitization and analysis of the film image.

PMID- 8130985
TI  - Case report: metastatic malignant testicular teratoma of the thymus.
AB  - Metastasis of malignant testicular teratoma to numerous sites is recognized and
      thymic hypertrophy following chemotherapy is frequently seen. The finding of
      metastatic malignant testicular teratoma in the thymus described here illustrates
      a further cause of thymic enlargement in this group of patients, which has not
      been previously reported.

PMID- 8130986
TI  - Case report: mesenteric arterial rupture following blunt abdominal trauma:
      demonstration by computed tomography.

PMID- 8130987
TI  - Case report: computed tomography findings in lipoid proteinosis: report of two
      cases.
AB  - Lipoid proteinosis (Urbach-Wiethe disease (Urbach, E and Wiethe, C, Lipoidosis
      cutis mucosae, Virchows Arch. Patholog. Anat., 273, 285-319 (1929)) is a rare
      generalized disease with autosomal recessive inheritance. It most often involves
      the skin and mucosal membranes of the aerodigestive tract; but also involves the
      central nervous system, lung, lymph nodes and striated muscles. We present the
      computed tomography findings in the cranium and larynx of two siblings with
      lipoid proteinosis.

PMID- 8130988
TI  - Case report: unusual ultrasonographic appearance of a solitary retroperitoneal
      neurofibroma.
AB  - A neurofibroma in the retroperitoneum with unusual ultrasonic findings is
      described. The ultrasonographic differential diagnosis with other abdominal
      neoplasms, clinical features and pathological findings are presented.

PMID- 8130989
TI  - Case report: radiology of stromal sarcoma of the breast with ossifying pleural
      metastases.
AB  - Stromal sarcoma of the breast is a rare tumour, the radiology of which has not
      been to our knowledge properly documented: the case presented returned to medical
      attention with a large, apparently calcifying pulmonary mass. This proved to be
      an ossifying pleural metastasis at thoracotomy, when a second smaller,
      unsuspected similar lesion was found. The radiological findings (including
      mammography and CT) are reviewed. The role of the radionuclide bone scan (the
      full significance of which was not appreciated preoperatively) is discussed.

PMID- 8130990
TI  - Case of the month: a case of forgetfulness?
AB  - An obese 24-year-old man was admitted following a road traffic accident, during
      which he crashed into several cars and a shop. He had not been drinking alcohol,
      yet did not recall the incident. The family had noticed recent odd behaviour,
      episodic aggression and a glazed look at times. Apart from a minor whiplash
      injury, he was uninjured and clinically normal. A computed tomography (CT) head
      scan and encephalo-electrography were both normal. Routine investigations were
      unremarkable apart from a fasting glucose 0.9 mmol l-1. In view of the presenting
      symptoms and fasting hypoglycaemia, a CT scan of the abdomen was performed
      (Figure 1). What does this show?

PMID- 8130991
TI  - Further experience at the Bristol Centre, following the installation of a second
      MRI unit.

PMID- 8130992
TI  - Malpositioned Hickman line: what to do when all else fails.

PMID- 8130993
TI  - Resistance and pulsatility Doppler indices: how accurately do they reflect
      changes in renal vascular resistance.

PMID- 8130994
TI  - Review article: computed tomography and magnetic resonance in the diagnosis of
      intraventricular cerebral masses.
AB  - We describe a series of 60 cases of patients with masses arising within the
      cerebral ventricles. The site and relative frequency is noted for each
      histological type. The differential diagnosis depends on patient age and sex,
      site, morphology and number of masses, presence and type of hydrocephalus and the
      characteristics of the mass on computed tomography (CT) and magnetic resonance
      (MR) images. A review of the literature has been performed and this information
      collated with our own experience to give detailed descriptions of the typical
      features of each intraventricular mass. Attention is drawn to intraventricular
      neurocytoma, a recently described tumour that may be mistaken histologically for
      intraventricular oligodendroglioma or ependymoma. A comparison is made of the
      value of CT and MR in the diagnosis of intraventricular masses.

PMID- 8130995
TI  - The value of the short tau inversion recovery sequence in magnetic resonance
      imaging of thyroid eye disease.
AB  - 22 patients with thyroid eye disease were examined with magnetic resonance
      imaging (MRI) and the results compared with 10 controls. Imaging was performed on
      a 1.0 T scanner using a head coil. All patients were examined using both T1W and
      short tau inversion recovery (STIR) sequences. The relative signal intensity (SI)
      of individual extraocular muscles were quantified by comparison with SI from the
      adjacent temporalis muscle to give a signal intensity ratio (SIR). The results
      were compared with clinical disease activity assessed by the Werner grading
      system. Visual evaluation of muscle size and calculated SIRs showed an increase
      when compared to normals in 15 of the 22 patients. This difference was
      significant in patients with high grade (4-6) clinical disease. The known
      histological changes in this disease suggest that this increase in signal is
      caused by oedema secondary to acute inflammation. STIR sequences suppress the
      retro-orbital fat and thus enhance these changes both in the muscles and in the
      fat itself. The MR findings suggest that the STIR sequence can be used to predict
      those patients that will respond to anti-inflammatory treatment.

PMID- 8130996
TI  - Plain chest radiographic changes of the absent pulmonary valve syndrome.
AB  - The plain chest radiographs of 40 patients with the absent pulmonary valve
      syndrome in association with tetralogy of Fallot have been reviewed. The
      conventional frontal projection showed characteristic changes of massively
      dilated central pulmonary arteries with normal peripheral markings in all
      patients (100%). Lobar hyperinflation was present in a significant proportion of
      the infant group (38%) which in a smaller group can be a complication requiring
      surgery in addition to that for the cardiac malformation.

PMID- 8130997
TI  - Relationship of computed tomography tumour volume to patient survival in
      carcinoma of the cervix treated by radical radiotherapy.
AB  - In this retrospective study tumour volume was calculated by two different methods
      from the staging computed tomographic scans obtained in 1987 of 20 patients with
      carcinoma of the cervix. All patients underwent treatment by radical radiotherapy
      and the survival figures at 5 years were analysed. The aim was to identify the
      nature of the relationship between the true tumour volume and tumour volume
      obtained by measuring the maximum dimensions in each plane ("cuboid" volume).
      Significant correlation between the product of height x width x depth and true
      tumour volume was demonstrated (r = 0.983). A multivariate analysis of survival
      demonstrated a significantly increased relative risk for positive nodes (p <
      0.03) and tumour depth > 3.8 cm (p < 0.04) or tumour width > 5.0 cm (p < 0.03). A
      significant difference (p < 0.02) between the median tumour volumes for early and
      late stage disease was present irrespective of the method used to calculate
      tumour volume. This study demonstrates that cuboid tumour volume can be a good
      reflection of the true volume; in addition, positive nodes, tumour depth and
      tumour width are significant determinants of survival.

PMID- 8130998
TI  - The reproducibility of bronchial circumference measurements using computed
      tomography.
AB  - Objective measurement of bronchial damage in patients with bronchiectasis is
      needed to identify progressive disease. This study evaluates the inter- and
      intraobserver variation in computed tomography (CT) measurements of bronchial
      wall circumference and examines the precision with which CT measurements of the
      bronchi can be repeated in patients with bronchiectasis. Twelve patients were
      scanned and the circumferences of 61 subsegmental bronchi were measured
      independently on two occasions, by three observers, using a tracing facility on
      the CT console. To determine the accuracy with which previously acquired sections
      could be repeated, five patients were scanned on two separate occasions. The mean
      bronchial circumference measured by the three observers was 16.1 +/- 8.3 mm. The
      standard deviations of differences between first and second measurements of
      bronchial circumference for the three observers (intraobserver variability) were:
      0.60 mm, 0.67 mm and 0.40 mm. The standard deviation of readings for
      interobserver variability was 0.71 mm. The standard deviations of differences
      (and coefficients of variation) for measurements of bronchial circumference
      following rescanning were: 1.82 mm, 1.40 mm and 1.74 mm (9.9%, 7.6% and 9.3%,
      respectively). The reproducibility of measurements of wall circumference, between
      and within observers and between examinations, indicates that such measurements
      may be clinically useful in demonstrating the progression of bronchiectasis.

PMID- 8130999
TI  - The value of shoulder distension arthrography with intraarticular injection of
      steroid and local anaesthetic: a follow-up study.
AB  - A series of 51 patients, seen in Leicester, with "frozen shoulder", and referred
      for arthrographic examination, were assessed both before and after distension
      arthrography, using air and a low-osmolar contrast media combined with a steroid
      and local anaesthetic injection. 38 attended for further assessment at up to 6
      months later. 16 patients were found to have a rotator cuff tear. There was no
      significant change in the mean range of active movement in the patients with
      rotator cuff tears, but symptomatic improvement ensued in 44% of cases. In those
      found to have no rotator cuff tear, and external rotation of less than 35
      degrees, a significant improvement in range of movement was seen. While those
      with less limitation of external rotation showed no change in their range of
      movement, they did experience symptomatic improvement in 73% of cases. We
      conclude that shoulder distension arthrography, with steroid and local
      anaesthetic injection, may be of symptomatic benefit in patients with frozen
      shoulder and without a rotator cuff tear, while only those with external rotation
      of less than 35 degrees are likely to improve their range of motion.

PMID- 8131000
TI  - Minimally invasive cancer surgery using focused ultrasound: a pre-clinical,
      normal tissue study.
AB  - Using a focused 1.7 MHz ultrasound field (focal length/transducer diameter ratio
      of 1.7) and in situ intensities spatially averaged within the half-pressure
      maximum contour in the range 100-400 W cm-2, ablative lesions have been
      prescriptively placed singly and in arrays, in the livers and bladder walls of
      adult female Large White pigs. Exposures were made through the skin with up to 8
      cm of intervening tissue. Ablative lesions were placed under ultrasonic guidance,
      and specific lesion echoes were subsequently observed in two cases. Animals were
      sacrificed immediately after induction of ultrasonic lesions, post-mortems were
      performed, as were histological examinations of normal and damaged tissue. There
      was clear demarcation between ablated and normal tissue. Provided that simple
      rules on exposure technique had been observed, there was no evidence of
      inadvertent tissue damage, either locally to the treatment site, or in the tissue
      lying between the source and the target. This study is a useful step in
      demonstrating the feasibility of clinical trials for the use of this technique in
      treating bladder tumours and solitary liver metastases.

PMID- 8131001
TI  - The development of an interdepartmental audit as part of a physics quality
      assurance programme for external beam therapy.
AB  - A cost-effective audit system has been developed that will both detect systematic
      error in data and procedures and evaluate the quality assurance programme
      provided by a physics department for radiotherapy. The audit has been developed
      for external beam radiotherapy and assesses one modality and one treatment
      machine per year. The audit is carried out on an interdepartmental basis and can
      be undertaken by two physicists from each department in one working day. The
      method of assessing the quality assurance programme and the schedule of
      measurements are described. The process is illustrated using the results of trial
      audits between the medical physics departments at Coventry and Leicester.

PMID- 8131002
TI  - Outcome of 249 patients attending a nuclear medicine department with well
      differentiated thyroid cancer; a 23 year review.
AB  - 249 patients with well differentiated thyroid cancer attended the Nuclear
      Medicine Department of the Royal Liverpool Hospital (formerly housed at the
      Liverpool Clinic) from 1967 to 1990. Papillary carcinoma was histologically
      evident in 68% of patients and follicular carcinoma in 32%. Fifteen percent of
      all patients died of their cancer. The extent of initial surgery did not appear
      to influence the recurrence of disease, nor the patient survival. Univariate
      analysis showed that males had a worse survival rate than females during the 5
      years after diagnosis but thereafter survival rates were similar. Multivariate
      analysis indicated that unfavourable survival factors were "age over 45 years at
      diagnosis" and "presence of distal metastases". Survival was not significantly
      different with or without 131I ablation where there were no distal metastases.
      Outcome of pregnancy after 131I ablation gave no cause for concern. No serious
      complications were observed following 131I therapy. Serum thyroglobulin tests
      were introduced only half way through the review period and were helpful in
      predicting the presence of tumour recurrence but these data are to be discussed
      in another communication.

PMID- 8131003
TI  - Biokinetics and dosimetry for [methyl-11C]thymidine.
AB  - The uptake and retention of [methyl-11C]thymidine in organs and tissues after
      intravenous injection were studied using positron emission tomography scanning of
      patients. In addition, clearance of 11C-activity from the blood was determined
      directly by measurements of blood-samples. 5 min after administration the
      activity level was already reduced to 5% of the initial activity after injection.
      Preferential uptake of 11C-activity was present in the liver and kidneys. A less
      pronounced uptake was observed in the skeletal muscle tissue, heart wall, lungs
      and salivary glands. The retention in these organs and tissues has a long half
      life compared with the physical half-life of 11C. The absorbed dose per unit
      activity administered was calculated for all critical organs following the
      Medical Internal Radiation Dose Committee formalism. Averaging over the patients,
      values of 37 and 28 microGy MBq-1 were obtained for the liver and the kidneys
      respectively. The committed effective dose after a [methyl-11C]thymidine scan
      with 740 MBq, a commonly applied amount of activity for this type of scan, is 2.8
      mSv.

PMID- 8131004
TI  - Technical note: room shielding requirements in diagnostic radiology.
AB  - New regulations propose a more stringent limit to the radiation exposure of
      workers and members of the public. The shielding in X-ray areas will have to be
      reassessed to take account of these new limits. This technical note identifies a
      computerized technique for evaluating shielding requirements which yields results
      that are significantly more cost effective than those determined by traditional
      methods.

PMID- 8131005
TI  - Case report: intracranial extramedullary haematopoiesis in postpolycythemic
      myelofibrosis.
AB  - Extramedullary haematopoiesis (EMH), which may occur in various types of
      haemodyscrasia and dyshaematopoiesis, is generally seen in the spleen, liver and
      lymph nodes, but rarely within the cranium. This is a case of intracranial EMH in
      a patient with secondary myelofibrosis which developed after the treatment of
      polycythaemia rubra vera.

PMID- 8131006
TI  - Case report: bone metastasis from cholangiocarcinoma showing unusual accumulation
      on bone scintigraphy and 67Ga scintigraphy.

PMID- 8131007
TI  - Case report: calcification within aneurysmal bone cyst.
AB  - Aneurysmal bone cyst (ABC) usually affects older children or young adults. The
      radiological appearance is of a purely osteolytic expansile metaphyseal lesion
      with thinned out cortex and internal septations. We present a case of ABC in a 5
      year-old girl which showed internal calcification and was initially diagnosed as
      enchondroma. However, pathological examination revealed typical appearance of ABC
      with large area of dystrophic calcification.

PMID- 8131008
TI  - Case report: ultrasound diagnosis of obstructed Roux loop after cancer of the
      pancreas or bile duct.
AB  - We describe three cases with known pancreatic or bile duct neoplasia treated by
      surgery who subsequently presented with obstructive jaundice. In all cases
      ultrasound demonstrated a fluid-filled obstructed Roux loop and a patent biliary
      enteric anastomosis. The cause of the obstruction was seen in two cases.
      Ultrasound is a safe, fast, reliable and non-invasive method in the assessment of
      these patients.

PMID- 8131009
TI  - Case of the month: communication makes all the difference.

PMID- 8131010
TI  - EMI patents on computed tomography: history of legal actions.

PMID- 8131011
TI  - EMI patent litigation in the US.

PMID- 8131012
TI  - Metastases from renal cell carcinoma to the humerus or the shoulder girdle.
AB  - OBJECTIVE: To discuss the clinical presentation of metastases in the scapula
      and/or humerus resulting from renal cell carcinoma and the courses of treatment
      available. PATIENTS: A series of 35 patients with humeral or scapular metastases
      from renal cell carcinoma, treated at The Norwegian Radium Hospital (NRH) during
      an 11-year period, is reviewed. Two case reports are examined in detail. RESULTS:
      The median survival was 12 months (range 1-88) from the time of diagnosis of
      metastasis. Three patients lived for more than 50 months. CONCLUSION: Owing to
      the relatively long survival time, especially in patients with limited tumour
      burden elsewhere and who are in a good general state of health, long-lasting
      palliative treatment of the humeral or scapular metastases is aimed for. Renal
      cell carcinoma tends to be resistant to radiotherapy, and early treatment,
      combining orthopaedic surgery and high-dose radiotherapy, is advocated.

PMID- 8131013
TI  - Does lithotripsy cause hearing loss?
AB  - OBJECTIVE: To determine whether lithotripsy with the Dornier MPL9000 has any
      significant effect on the hearing of either patients or operators, as determined
      by pure tone audiometry. PATIENTS AND METHODS: Twenty patients had audiometry
      prior to a single exposure to lithotripsy and one hour after treatment. Staff
      were monitored on a 3 monthly basis. RESULTS: No evidence was found to suggest
      that single or repeated exposure to the noise emitted by this Dornier
      lithotripter was associated with any hearing loss. CONCLUSIONS: These results
      suggest that the risk to the hearing of patients exposed to lithotripter noise is
      negligible. Cochlear damage resulting from excessive noise depends on both the
      intensity of the sound and the duration of exposure. The acoustic properties of
      the building housing the machine may also be important and can significantly
      influence the intensity of the sound at the ear. At marginal levels it may be
      years before the deficit reaches a level that can be detected by subjective
      audiometry. In addition, susceptibility to noise induced hearing loss is
      difficult to predict. Although these results suggest that there is minimal risk
      to the hearing of staff members exposed to lithotripter noise, the authors
      recommend that staff exposed to repeated lithotripter noise over long periods
      undergo regular audiometric assessment (including a preemployment baseline
      assessment) to identify evidence of noise induced auditory trauma, and that
      protective equipment be worn by staff members to reduce the possibility of long
      term damage.

PMID- 8131014
TI  - Impact of sodium-potassium citrate on the diurnal variations in urinary calcium
      oxalate and calcium phosphate saturation levels in normal individuals.
AB  - OBJECTIVE: To study the effects of treatment for 5 days with sodium-potassium
      citrate (1 g three times a day (t.i.d.), 1 g four times a day (q.i.d.), or 3 g
      three times a day (t.i.d.)) on the diurnal variations of urinary calcium
      containing lithogenic substances. SUBJECTS AND METHODS: Five healthy men
      participated in the study, in which the calcium oxalate (CaOx), octacalcium
      phosphate (OCP), hydroxyapatite (HAP), and brushite (Bru) urinary saturation
      levels in fractional urine samples were determined before and during treatment.
      RESULTS: The CaOx and Bru saturation levels, as estimated from the AP(CaOx) and
      AP(Bru) indices (Tiselius) respectively, peaked between 05.30 and 08.00 hours,
      and the peaks were blunted by each treatment regimen in comparison with the
      control day. In particular, the 1 g q.i.d. regimen significantly decreased the
      CaOx saturation level between 05.30 and 08.00 hours. The OCP and HAP saturation
      levels, as estimated from the AP(CaP) index (Tiselius), peaked between 08.00 and
      10.30 hours, and the levels were increased by each regimen. In particular, the
      OCP level exceeded the formation product between 08.00 and 10.30 hours on day 5
      in all regimens. CONCLUSION: An evening dose of sodium-potassium citrate in
      addition to the conventional t.i.d. regimen may reduce the early-morning urinary
      CaOx and Bru saturation levels whilst keeping OCP and HAP saturation within
      acceptable limits. In contrast, a morning dose may cause OCP saturation to exceed
      the formation product. Although the OCP saturation level during treatment was not
      significantly higher than the level before treatment, this slight increase might
      be critical.

PMID- 8131015
TI  - Rapid diagnostic service for patients with haematuria.
AB  - OBJECTIVE: To assess the feasibility of a clinic for the investigation of
      haematuria, with open access to general practitioners. PATIENTS AND METHODS: A
      total of 395 patients (198 men and 197 women), with mean age 51 years (range 19
      73), were referred from 13 general practitioner clinics. All investigations were
      performed at the patient's first visit at which time either a provisional or a
      definitive diagnosis was made. RESULTS: Urinary tract infection was the most
      common diagnosis. Of all the patients, 43 (11%) had a malignancy of whom nine
      presented with microscopic haematuria. Fifty-nine per cent of patients were
      discharged after their first visit and 26% were placed on the waiting list for in
      patient procedures. CONCLUSION: An open access clinic such as this is efficient
      and easily run. The high incidence of pathological abnormalities makes it a
      worthwhile facility.

PMID- 8131016
TI  - Same day diagnostic service for new cases of haematuria--a district general
      hospital experience.
AB  - OBJECTIVE: To describe the running of a special haematuria diagnostic service
      which catered for a flexible cystoscopy on the same day as the first clinical
      visit. The impact of this service especially with regard to the timing of the
      intravenous urogram (IVU) is discussed. The service was designed to facilitate
      early diagnosis, particularly of bladder tumours, in new cases of haematuria.
      Potentially this would allow a more effective planning of operating lists and
      implementation of early definitive treatment. PATIENTS AND METHODS: Within the
      setting of a District General Hospital, new cases of haematuria were studied (42
      male, 29 female, mean age 60 +/- 13 years). Fifty-one had a pre-clinic IVU
      whereas 20 had this deferred until after their first visit. All patients
      underwent a flexible cystoscopy under local anaesthesia on their first visit. New
      cases of bladder cancer were placed on the next available list for definitive
      treatment whilst patients with normal cystoscopy were referred back to the clinic
      for further investigations. RESULTS: Altering the timing of the IVU helped in
      reducing hospital delay from 33 +/- 19 days (range 9-92 days) to 22 +/- 9 days
      (range 8-52 days; P < 0.04); the number of diagnostic cystoscopies performed
      within 4 weeks increased from 65% to 95%. CONCLUSION: The same day diagnostic
      service has not been difficult to administer. Patient acceptability was excellent
      and design objectives were achieved.

PMID- 8131018
TI  - Multiple bladder biopsies under intravesical lignocaine anaesthesia.
AB  - OBJECTIVE: To study biopsy quality, complications and patient acceptance when
      urinary bladder biopsies were taken under local anaesthesia. PATIENTS AND
      METHODS: Multiple large cold-cup urinary bladder biopsies were taken under
      topical lignocaine anaesthesia in 20 patients who had previously undergone
      transurethral resection for superficial bladder cancer. RESULTS: The procedures
      were carried out at the outpatient clinic with 0.5-2 h post-operative
      observation. Patient acceptance was very high and complications were minimal. The
      quality of the biopsies was consistently high and influenced treatment in the
      majority of the patients. CONCLUSION: In our department multiple bladder biopsies
      (mapping) have previously always been performed as a transurethral resection
      under general or spinal anaesthesia. Operation under intravesical lignocaine
      anaesthesia with 2 h post-operative observation reduced the costs by 70%.

PMID- 8131017
TI  - Flexible cystoscopy in men: is topical anaesthesia with lignocaine gel
      worthwhile?
AB  - OBJECTIVE: The value of 2% lignocaine gel as a topical anaesthetic for flexible
      cystoscopy in men was tested in a prospective, randomized, double-blind, placebo
      controlled trial. PATIENTS AND METHODS: A total of 138 patients were entered into
      the study. Group A patients (n = 75) received 10 ml of 2% lignocaine gel
      intraurethrally whilst 10 ml of plain lubricating gel was instilled in the
      remaining 63 patients (Group B). Patient discomfort was recorded by means of a
      four-point descriptive pain scale (completed by both surgeon and patient) and a
      100 mm non-graphic rating visual analogue scale (patient only). RESULTS: The
      results showed no significant difference between the two treatments irrespective
      of the method of recording. CONCLUSION: This study shows that 2% lignocaine gel
      offers no advantage over plain lubricating gel in providing analgesia for
      flexible cystoscopy. In this situation good lubrication may be a more important
      factor than topical anaesthesia.

PMID- 8131019
TI  - Should random urothelial biopsies be taken from patients with primary superficial
      bladder cancer? A decision analysis. Members of the Dutch South-East Co-Operative
      Urological Group.
AB  - OBJECTIVE: To evaluate whether it is worthwhile to implement routine random
      biopsies from the normal-looking urothelium in the management of patients with
      primary superficial bladder cancer. PATIENTS AND METHODS: Two hypothetical
      management policies were compared, one of which incorporated random biopsies as
      an additional prognostic test. In the 'no-biopsy policy', all patients were
      treated with transurethral resection (TUR) alone, except for patients with a
      pT1G3 tumour who were treated with adjuvant prophylactic intravesical therapy. In
      the 'biopsy policy', the choice of treatment was influenced by the presence or
      absence of dysplastic urothelium in random biopsy specimens, except in patients
      with a pT1G3 tumour who received adjuvant treatment, irrespective of the result
      of random biopsies. Decision analysis was used to compare the outcome of these
      hypothetical policies with respect to the expected 3-year risks of recurrence and
      progression. Baseline data used in the analysis originated from a large
      unselected case series, prospectively documented in the Netherlands. RESULTS: The
      'biopsy policy' resulted in a 3 year risk of recurrence and a 3 year risk of
      progression of 52% and 11%, respectively. These 3 year risks were almost
      identical to the 'no-biopsy policy': 54% and 11%, respectively. In a sensitivity
      analysis, the expected 3 year risks of recurrence as well as the expected 3 year
      risks of progression were found to remain similar with both policies, even with
      quite extreme assumptions favouring the 'biopsy policy'. CONCLUSION: In view of
      the expected small difference in disease outcome between the two management
      policies, taking random biopsies of normal-looking urothelium at the time of the
      TUR has no practical value.

PMID- 8131020
TI  - The influence of review pathology on study outcome of a randomized multicentre
      superficial bladder cancer trial. Members of the Dutch South East Cooperative
      Urological Group.
AB  - OBJECTIVE: To determine whether differences between local and review pathology in
      a multicentre study influence the results of treatment and results from
      prognostic factor analysis. PATIENTS AND METHODS: A randomized multicentre study
      in superficial bladder cancer is reported, in which the influence of local and
      review pathology on the study outcome was investigated. RESULTS: The conformity
      between local and review pathology of the pT category was 79.3%, of the grade
      70.2%, and the combination of both 59.7%. In local pathology, undergrading was
      more frequent than overgrading and overstaging more frequent than understaging.
      However, the risks of recurrent disease in the separate stage and grade groups
      remained the same after correcting the pathology result. A prognostic factor
      analysis with regard to the risk of recurrent disease was carried out. The Cox
      hazard ratios of tumour localization, multiplicity, patient age (significant
      factors), tumour grade, size, history and gender (not significant) remained
      almost the same after correction for review pathology. Only the prognostic
      relevance of tumour stage increased after pathology correction. CONCLUSION: We
      conclude that, although review pathology caused considerable changes in the
      pathology results, this did not change the results of treatment, and hardly
      altered the results of a prognostic factor analysis in this randomized study.

PMID- 8131022
TI  - Non-visualization versus normal appearance of cavernous arteries on selective
      internal pudendal pharmaco-angiograms: comparison with duplex scanning,
      cavernosal artery systolic occlusion pressure and penile brachial index.
AB  - OBJECTIVE: To determine whether selective internal pudendal pharmaco-angiography
      (SIPA) is the most reliable diagnostic procedure for evaluating the function of
      the cavernosal arteries. PATIENTS AND METHODS: Both sides of the selective
      internal pudendal pharmaco-angiogram taken in 35 patients (70 cases), whose
      history was suggestive of post-traumatic arteriogenic impotence, were evaluated
      separately and compared to the corresponding side using the penile brachial index
      (PBI), duplex scanning and cavernosal artery systolic occlusion pressure (CASOP).
      RESULTS: There was no significant difference in the peak flow velocity and
      diameter changes of the cavernosal arteries on duplex scanning, in pressure
      differences between the brachial artery systolic pressure and the CASOP, and in
      the PBI between the group with a normal appearance on SIPA and the other where
      the cavernosal arteries were not visualized. There was no significant difference
      in the results of these functional evaluations between the normal group and cases
      where the cavernosal arteries were not visualized accompanied by a completely
      obstructed internal pudendal artery or common penile artery visible on SIPA.
      CONCLUSIONS: This study is unable to confirm the value of SIPA in evaluating the
      function of the cavernosal arteries as it provides only anatomical information.

PMID- 8131021
TI  - Extirpation and fulguration of multiple superficial bladder tumour recurrences
      under intravesical lignocaine anaesthesia.
AB  - OBJECTIVE: To register the results, complications and patient acceptance of
      bladder tumour operations under local anaesthesia. PATIENTS AND METHODS:
      Intravesical lignocaine was the anaesthesia used in 30 patients with multiple
      bladder tumour recurrences. The largest tumour was extirpated with large flexible
      biopsy forceps and the others were fulgurated. RESULTS: All visible tumours were
      extirpated or fulgurated except in one patient, where the operation had to be
      terminated due to unsatisfactory anaesthesia. All left the hospital within 2 h of
      surgery. Complications were minor and patient acceptance was very high.
      CONCLUSION: These operations have previously been performed under spinal
      anaesthesia in this department and the present modification reduced costs by
      approximately 70%. Patients who had only minor discomfort associated with routine
      cystoscopy under urethral anaesthesia were well suited for extirpation and
      fulguration of multiple small tumours under intravesical lignocaine.

PMID- 8131023
TI  - Urethral sensitivity in the aetiology of sensory urgency.
AB  - OBJECTIVE: To investigate urethral hypersensitivity as a cause of sensory
      urgency. PATIENTS AND METHODS: Twenty women with sensory urgency and 10 normal
      controls were enrolled in the study. A urethral conductance catheter was designed
      comprising three pairs of electrodes. These were accurately located in the
      urethra using the principle of urethral electrical conductance. The urethral
      sensory threshold was then measured at three sites along the urethral by applying
      a stimulatory current across each pair of electrodes in turn. RESULTS: The women
      with sensory urgency had significantly higher thresholds for urethral stimulation
      along the whole urethra when compared with the control group. CONCLUSION:
      Urethral hypersensitivity was not found to be a feature of sensory urgency and in
      fact the converse was demonstrated. This has not been described before. High
      sensory thresholds may occur with small fibre peripheral neuropathies. Thus,
      peripheral neuropathy is potentially a factor in the, as yet unknown, aetiology
      of sensory urgency.

PMID- 8131024
TI  - Colovaginoplasty in infants and children.
AB  - OBJECTIVE: To develop a technique of vaginoplasty suitable for use in children
      with vaginal insufficiency, without the need for lubrication and regular
      dilatation. Enteric segment vaginoplasty, previously reported in adolescents and
      adults, does not require dilatation and has growth potential unlike current
      methods, involving skin flaps or free grafts. PATIENTS AND METHODS: We report the
      use of a segment of sigmoid colon in seven consecutive children (age range 4
      months to 16 years). The diagnoses included congenital adrenal hyperplasia (1),
      androgen insensitivity syndrome (3), and vaginal agenesis (3). RESULTS: The mean
      post-operative hospital stay was 8 days (6-10 days) and there was no peri
      operative mortality or morbidity. At follow-up examination all children had an
      excellent cosmetic appearance without excessive mucus discharge. The oldest two
      girls required finger dilatation for mild colocutaneous stenosis. CONCLUSION: The
      surgery was completed before the age of 16 months in the three cases referred
      early. Though the follow-up is short it is hoped that this will minimize the
      emotional disturbance suffered by the child and parents faced with this problem.
      We have found colovaginoplasty to be a technically straightforward procedure with
      minimal morbidity suitable for use in infants and children. We await long-term
      follow-up to confirm this procedure to be the operation of choice in paediatric
      patients.

PMID- 8131025
TI  - Reconstruction of penoscrotal transposition.
AB  - OBJECTIVE: To assess the results of surgical correction of incomplete penoscrotal
      transposition and its impact on subsequent definitive urethroplasties and the
      final outcome. PATIENTS AND METHODS: The medical records of 22 patients who had
      undergone surgical correction for incomplete penoscrotal transposition at one
      centre in the last 8 years were evaluated retrospectively. The surgical technique
      is described and the outcome after correction is noted. RESULTS: All cases had
      severe hypospadias and approximately half had associated anomalies. No major
      complication occurred following surgery and the appearance of the external
      genitalia was satisfactory as judged both by the surgeons and patients. Operative
      scars did not constitute major handicaps for the subsequent urethroplasties.
      Sixteen patients have completed reconstructive surgery of whom 12 have glandular
      and four coronal meatuses. CONCLUSION: Reconstruction of penoscrotal
      transposition yielded satisfactory results in terms of cosmetic appearance and
      functional external genitalia, and is recommended before definitive
      urethroplasty.

PMID- 8131026
TI  - New technical expedient for epididymovasostomy.

PMID- 8131027
TI  - The Skyhook.

PMID- 8131028
TI  - Primary signet-ring cell carcinoma of the bladder.

PMID- 8131029
TI  - Delayed presentation of ureteric injury following arthrodesis of the hip joint.

PMID- 8131030
TI  - Carcinoma of the prostate presenting as cystic pelvic mass.

PMID- 8131031
TI  - Duplex ureters: a pitfall during ileal conduit urinary diversion.

PMID- 8131032
TI  - Intraperitoneal rupture of an infected urachus.

PMID- 8131033
TI  - Carcinoma of the prostate in a transsexual.

PMID- 8131034
TI  - Massive dilatation of an augmented bladder mimicking spontaneous perforation.

PMID- 8131035
TI  - Bladder leiomyosarcoma in a child: a 6 year follow-up.

PMID- 8131036
TI  - A self-made diagnosis of phaeochromocytoma of the urinary bladder.

PMID- 8131037
TI  - Responses of the human neurogenic bladder to KCl, carbachol, ATP and CaCl2.

PMID- 8131038
TI  - Abnormal pattern of cerebral glucose metabolic rates involving language areas in
      young adults with Down syndrome.
AB  - Correlational and discriminant analyses were applied to "resting" state (eyes
      covered, ears plugged) regional cerebral glucose metabolic data, obtained with
      positron emission tomography (PET) and [18F] fluorodeoxyglucose in 14 retarded
      adults with Down syndrome (10 men, 4 women; age 26-38 years) and 17 age- and sex
      matched controls. Down and control subjects showed no differences in the pattern
      of correlations. However, a discriminant function, reflecting regional
      interactions involving primary language areas, successfully classified the Down
      (100%) and control (88%) subjects. The results are consistent with a disruption
      of brain regional interactions involving language areas in adults with Down
      syndrome.

PMID- 8131039
TI  - Target-related neologism formation in jargonaphasia.
AB  - Neologistic demisyllables produced by three subjects with jargonaphasia
      (Christman, 1990, 1992) were compared to target demisyllables to determine
      whether phonological patterns underlying target-related neology could be captured
      by the Sonority Sequencing Principle independently of phonotactics. Results
      revealed that substitution errors replaced most intended segments with
      obstruents, despite the absence of phonotactic restrictions that might have
      conditioned the errors. Findings suggest a default pattern of segment selection
      to which the phonological system reverts when normal processing is otherwise
      blocked.

PMID- 8131040
TI  - The content of narrative discourse in children and adolescents after early-onset
      hydrocephalus and in normally developing age peers.
AB  - The development of narrative content was studied in 100 children aged 6-15 years
      (49 with early-onset hydrocephalus and 51 age-matched controls) by analyzing
      transcripts of oral texts produced from their narrations of two fairy tales. In
      relation to those of their age-matched peers, the narratives of the children with
      hydrocephalus were less cohesive and less coherent. They conveyed less of the
      content needed for the narrative message, included more referentially ambiguous
      material, included uninterpretable or implausible content, and were more verbose
      and less economic in quality. In relation to their age-matched peers, then,
      children with hydrocephalus produce narratives that are difficult to process,
      unclear, uneconomic, and less fully elaborated for meaning. These data add to an
      emerging body of information that shows children and adolescents with early-onset
      hydrocephalus to be at risk for several types of discourse and pragmatic
      impairments. The language of children with hydrocephalus is discussed with
      reference to the theoretical distinction between interpersonal pragmatic
      conventions and constraints relating to textual rhetoric (processability,
      clarity, economy, and expressivity). By showing impaired textual rhetoric
      coexisting with apparently preserved interpersonal rhetoric in individuals with
      developmental anomalies of brain development, the present data provide some
      support for a functional dissociation between the two classes of pragmatic
      constraints.

PMID- 8131041
TI  - Auditory neglect and the ear extinction effect in dichotic listening: a reply to
      Beaton and McCarthy (1993).
AB  - In our reply to Beaton and McCarthy (1993), we argue that the issue of ear
      extinction in dichotic listening also should take into account lesion site and
      lesion extension. When the lesion is primarily affecting the auditory pathways,
      the resulting dichotic dysfunction may be an ear extinction effect. However, when
      the lesion is outside of the auditory system, the absence of reports from one ear
      may be part of a larger cognitive deficit, involving more complex processes, like
      orientation and attention. Thus, by constraining the definition of an "ear
      extinction effect" to a perceptual deficit, Beaton and McCarthy confounds the
      issue of ear extinction with auditory neglect. In our reply we also present some
      new data from a patient with a left-sided thalamic pulvinar lesion, contrasting
      his dichotic listening performance with the patient reported in our original 1991
      study.

PMID- 8131042
TI  - Morphological processing in Italian agrammatic speakers syntactic implementation
      of inflectional morphology.
AB  - Most current linguistic and psycholinguistic characterizations of agrammatic
      production start from the observation that in spontaneous speech inflectional
      suffixes are either dropped or substituted by default forms, depending on the
      morphological structure of the language. So far, little experimental evidence has
      entered theory construction. In this paper, elicited data of two Italian patients
      with agrammatic speech are presented. The tasks involved the production of a past
      participle suffix in different sentence contexts. In Italian, the past participle
      has to agree in gender and number with the grammatical features of an antecedent
      noun, pronoun, or empty element. It is shown that both patients mastered the
      general principles of the agreement rule, and that they could produce correct
      inflectional suffixes in several tasks. Furthermore, the point of breakdown in
      their performance was syntactic rather than morphological, namely, when there
      were no overt morphological cues for the identification of the thematic roles in
      the sentence. These data cannot be accounted for by theories formulated in terms
      of the syntactic or postsyntactic deletion of suffixes or the functional elements
      underlying their realization. At least for the patients in this study,
      morphological substitutions arose as a result of an impairment in the syntactic
      processing of content words rather than functors.

PMID- 8131043
TI  - Effects of typeface characteristics on visual field asymmetries for letter
      identification in children and adults.
AB  - The current study compared the effects of three typeface characteristics (script
      likeness, or resemblance to cursive writing; confusability, or likelihood of
      confusing one letter with another; and difficulty, as indexed by naming latency)
      on letter identification in a divided visual fields test. It also asked whether
      and how these effects change with subject age. Subjects were 48 right-handed 9-
      and 14-year-old boys and undergraduate men--16 in each age group. They orally
      identified single letters in eight different typefaces presented
      tachistoscopically to the left or right visual hemifield. The difference between
      hemifields in threshold presentation time was the dependent measure. For all
      ages, the direction and degree of the visual field advantage changed with
      typeface complexity (a composite index of the three characteristics), with the
      simplest typeface yielding a right visual field/left hemisphere advantage, and
      with two of the most complex typefaces yielding a left visual field/right
      hemisphere advantage. There were age differences, though, in the relative
      contribution of the individual characteristics to this effect. For
      undergraduates, the strongest predictor of right hemisphere participation was
      script-likeness, whereas for 9- and 14-year-olds it was typeface difficulty.

PMID- 8131044
TI  - Regional cerebral blood flow in sign language users.
AB  - Cerebral activation was compared during sign and spoken language comprehension.
      Nine hearing children of deaf parents were studied and the cerebral activation
      was measured by recordings of the regional cerebral blood flow. Comprehension of
      a complex material gave a bilateral activation of posterior temporal regions for
      both spoken and signed language. It seems that sign language activates the cortex
      in a way which is very similar to spoken language, when the listener watches the
      speaker. Cortical areas usually regarded to be important for spatial ability do
      not show enhanced activation during sign language perception.

PMID- 8131045
TI  - Sequences of phonemic approximations in a Thai conduction aphasic.
AB  - Sequences of phonemic approximations (SPAs) to a single target word on a picture
      naming task were investigated in a Thai-speaking conduction aphasic. A corpus of
      207 SPAs was analyzed with an adaptation of Valdois, Joanette, and Nespoulous's
      (1989) methodology to a tone language. Measures included the length of SPAs,
      overall degree of approximation to the target of the last attempt and each of the
      preceding attempts, as well as degree of approximation to the target in terms of
      number of syllables, syllable structure, segments (consonants/vowels), and tones.
      Results indicated that there was a steady progression toward the target
      regardless of eventual outcome or length of sequence. Number of syllables of the
      target word was better preserved than syllable structure, and tones better than
      segments. In the course of SPAs, tonal information was accessed earlier than
      segmental, and syllabic length information earlier than syllabic structure.
      Within SPAs, tonal information was more stable than segmental across successive
      approximations. Findings are discussed in relation to a functional model of
      single word production and multidimensional phonological representations.

PMID- 8131046
TI  - Brain lesions, central masking, and dichotic speech perception.
AB  - A dichotic CV syllables task and an auditory central masking task were
      administered to 10 right hemisphere stroke, 10 left hemisphere stroke, and 10 age
      matched controls. When data for all subjects were considered within and across
      groups, it was found that lateralized performance measures for dichotic listening
      and central masking were highly correlated (r = .647, p < .05 for controls; r =
      .810, p < .005 for R-CVA; r = .648, p < .05 for L-CVA; r = .833, p < .0001 for
      all subjects). The data suggest that some aspects of dichotic performance that
      have been previously attributed to changes in verbal processing are more
      adequately explained as being the result of a general binaural asymmetry of
      auditory perception.

PMID- 8131047
TI  - Diffusion analysis of valproate and trans-2-en-valproate in agar and in cerebral
      cortex of the rat.
AB  - The diffusion of valproate (VPA) and trans-2-en-valproate were studied in agar
      gel and in the cerebral cortex of the rat using pressure microejection and VPA
      selective microelectrodes. From the agar measurements a free diffusion
      coefficient for VPA of 6.52 x 10(-6) cm2.s-1 and for trans-2-en-VPA of 5.25 x 10(
      6) cm2.s-1 for 37 degrees C was determined. The tortuosity value in the cortex
      was 1.92 for VPA and 1.67 for trans-2-en-VPA. The tortuosity values suggest that
      VPA and trans-2-en-VPA diffuse mainly in the extracellular space of the brain.

PMID- 8131048
TI  - Changes in early 'automatic' postural responses associated with the prior
      planning and execution of a compensatory step.
AB  - There is growing interest in the perturbation-evoked stepping response as an
      important element in the movement repertoire to maintain upright stance. It is
      possible that there is an important relationship between the well-documented,
      early 'automatic' postural responses and subsequent stepping responses. In this
      study, we characterize changes in early 'automatic' postural responses associated
      with the prior-planning and execution of a compensatory (i.e. stabilizing)
      stepping response. Seven subjects were tested on a 'moveable' platform which
      could translate in the anterior-posterior direction. The subjects' responses were
      analyzed for two different tasks: (1) 'constrained' (keep feet in place), and (2)
      perturbation-cued 'reaction time' stepping (step when the platform moves). Only
      responses to forward platform translations were analyzed in this study. Responses
      for each of these tasks were evoked using two different perturbation magnitudes.
      The higher magnitude was sufficiently large to evoke stepping responses in a
      large proportion of the 'constrained' trials despite instructions not to step. We
      compared the magnitude of the early evoked postural reactions between trials when
      subjects had pre-planned a stepping response against trials characterized by
      either (1) no stepping or (2) unplanned stepping responses. The results revealed
      that the early 'automatic' responses in tibialis anterior were always present in
      all subjects and all tasks. However, the evoked 'automatic' responses were
      approximately 36% smaller (over the first 50 ms) when followed by a pre-planned
      stepping response ('reaction-time' task). This task-related difference was
      similar for both perturbation magnitudes i.e. it occurred regardless of whether
      the 'constrained' tasks involved feet-in-place responses (small perturbations) or
      stepping responses (large perturbations).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131049
TI  - Angiotensin II receptor subtypes and angiotensin-converting enzyme in the fetal
      rat brain.
AB  - Angiotensin II (ANG II) receptor subtypes (AT1, displaced by losartan, and AT2,
      displaced by CGP 42112A) were characterized by quantitative autoradiography after
      incubation with the ANG II agonist [125I]Sar1-ANG II, in specific brain nuclei of
      19-day-old rat embryos. Binding to AT1 receptors, located in the subfornical
      organ, paraventricular nucleus, nucleus of the solitary tract and choroid plexus,
      was sensitive to incubation with GTP gamma S. The sensitivity of AT2 receptors to
      GTP gamma S was heterogeneous. In the ventral thalamic, rostral hypoglossal and
      medial geniculate nuclei, and in the locus coeruleus, binding to AT2 receptors
      was sensitive to GTP gamma S and these areas belong to the AT2A subgroup.
      Conversely, in the inferior olive, medial (fastigial) cerebellar nucleus and
      caudal part of the hypoglossal nucleus, areas belonging to the AT2B subgroup,
      binding was insensitive to GTP gamma S. AT2 receptors were also present in
      cerebral arteries. In the fetal anterior pituitary, AT1 receptors predominated.
      The angiotensin-converting enzyme (ACE; EC 3.4.15.1) was studied by
      autoradiography with the selective inhibitor [125I]351A. In 19-day-old embryos,
      ACE was highly expressed in choroid plexus, with high concentrations in
      subfornical organ, posterior pituitary and cerebral arteries. No ACE binding was
      detected in extrapyramidal structures or anterior pituitary in 19-day-old
      embryos.

PMID- 8131050
TI  - The electrophysiological consequences of electrode impalement of peripheral
      nerves in the rat.
AB  - Peripheral nerve fascicles are deliberately impaled during microneurography
      experiments. We have assessed conduction block under these circumstances. First
      we recorded compound action potentials (CAP) in the sural nerve following
      stimulation of the sciatic nerve. The insertion of injection and microneurography
      electrodes between stimulation and recording sites produced a 20% decrease in the
      size of the CAP, which was maintained for the 10 min duration of impalement.
      After withdrawal, the conduction block partially resolved. In other experiments,
      single-unit action potentials were recorded from L4 and L5 dorsal roots following
      peripheral nerve stimulation. Microneurography electrodes inserted into the
      sciatic nerve produced conduction block in 50% of these axons. When axons were
      blocked, anodal stimulation through the tungsten electrode became more effective
      than cathodal stimulation. These results suggest that a temporary conduction
      block occurs in a significant number of myelinated fibers near the site of an
      inserted electrode.

PMID- 8131051
TI  - Effects of chronic ethanol on cholinergic actions in rat hippocampus:
      electrophysiological studies and quantification of m1-m5 muscarinic receptor
      subtypes.
AB  - The effects of chronic ethanol treatment (CET) on cholinergic modulation of CA1
      evoked field potentials and recurrent inhibition were investigated in rat
      hippocampal slices. Densities of muscarinic receptor subtypes were quantified in
      remaining hippocampal tissue by immunoprecipitation. Iontophoretic application of
      ACh in stratum pyramidale results in facilitation of single evoked population
      spikes; application in stratum radiatum results in depression of field EPSPs. CET
      decreased cholinergic facilitation of population spikes, while cholinergic
      inhibition of field EPSPs remained unaffected. Integrity of feedback (recurrent)
      inhibitory circuitry was evaluated by paired-pulse stimulation. As previously
      demonstrated, recurrent inhibition was significantly reduced after CET;
      cholinergic disinhibition was also significantly reduced. Thus, CET appears to
      disrupt a subset of cholinergic effector systems within hippocampal neurons. The
      reductions in cholinergic function produced by CET does not appear to be due to
      receptor loss, since muscarinic receptor subtype densities were not found to be
      significantly altered in this tissue. These results support the hypothesis that
      muscarinic receptor function is impaired in CA1 pyramidal cells through a
      disruption of intracellular signal transduction mechanisms. While it is unclear
      whether cholinergic function is reduced in interneurons directly, these results
      suggest that modulation of neuronal firing in the hippocampus is markedly altered
      following CET due to impairment of both cholinergic and GABAergic systems.

PMID- 8131052
TI  - Rabbit cerebellar slice analysis of long-term depression and its role in
      classical conditioning.
AB  - Cerebellar long-term depression (LTD) has been proposed as a mechanism underlying
      classical conditioning of the rabbit nictitating membrane/eyelid response (NMR).
      However, LTD has only been obtained reliably when (1) cerebellar slices are
      bathed in GABA antagonists which abolish disynaptic inhibitory post synaptic
      potentials, and (2) the temporal sequence of stimulation used in slice or intact
      preparations is the opposite of that used in classical conditioning. Based on
      intradendritic Purkinje cell recordings obtained from rabbit cerebellar slices,
      we report that stimulation of climbing fibers and then parallel fibers in the
      presence of the GABA antagonist, bicuculline, produced significant depression of
      parallel fiber excitatory post synaptic potential (epsp) amplitude that continued
      to increase for at least 20 min after stimulation. However, application of the
      same stimulation protocol without GABA antagonists produced a brief depression of
      parallel fiber epsps that disappeared within minutes. Activation of parallel
      fibers and then climbing fibers in an order opposite to the LTD-producing
      sequence (i.e. a classical conditioning-like order) produced a brief depression
      that dissipated quickly. Stimulation of parallel fibers alone produced a small,
      slowly developing potentiation, but stimulation of parallel fibers during
      depolarization-induced local dendritic calcium spikes produced significant
      depression almost immediately which then declined slowly to more modest levels.
      Finally, stimulation of parallel fibers at frequencies used in in vivo parallel
      fiber-climbing fiber stimulation experiments (e.g. 100 Hz) produced an immediate
      and profound long-lasting epsp depression. The depression occurred, however,
      whether parallel and climbing fibers were stimulated separately (unpaired) or in
      a classical conditioning-like protocol (paired) where parallel fiber stimulation
      coterminated with climbing fiber stimulation (10 Hz).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8131053
TI  - Glial response to neuronal activity: GFAP-mRNA and protein levels are transiently
      increased in the hippocampus after seizures.
AB  - We have recently demonstrated that electrically induced seizures lead to dramatic
      increases in mRNA for GFAP in areas in which seizures occur. The present study
      evaluates the time course of the changes in the GFAP-mRNA levels after seizures
      and the relationship between these changes and GFAP protein levels to understand
      the role of neuronal activity in regulating glial gene expression. GFA protein
      and mRNA levels were measured in hippocampi from rats in which seizures were
      induced by: (1) 50-Hz stimulus trains delivered 12 times over the course of 1 day
      via indwelling electrodes implanted chronically in the CA3 region of the
      hippocampus; and (2) intraperitoneal injections of pentylenetetrazol. In the case
      of the electrically induced seizures, we also compared the glial response in
      animals that had never experienced a seizure with the response in animals that
      previously had been kindled but had not experienced a seizure for 30 days.
      Electrically induced seizures led to rapid transient increases in GFAP-mRNA
      levels in the hippocampus ipsi- and contralateral to the stimulation. GFAP-mRNA
      increased about five-fold 1 day after the end of seizure activity and returned to
      near-control levels by 4 days. There were no detectable increases in GFA protein
      at 1 day but by 2 days GFA protein levels had increased about two-fold. GFA
      protein levels remained elevated until 4 days poststimulation and then began to
      decrease. The responses were similar when seizures were induced in kindled
      animals, except that the GFAP protein levels remained elevated for somewhat
      longer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131054
TI  - Synchronism of pressor response and grooming behavior in freely moving, conscious
      rats following intracerebroventricular administration of ACTH/MSH-like peptides.
AB  - After the i.c.v. administration of 300 pmol ACTH-(1-24) or [Nle4,D-Phe7]alpha
      MSH, a long-lasting increase in blood pressure was observed synchronously with
      the incidence of excessive grooming. Two structurally related peptides with no
      grooming behavior-inducing potency, ACTH-(7-16)-NH2 and gamma 2-MSH, in doses of
      300 and 500 pmol, respectively, caused a slight and short-lasting increase in
      blood pressure or had no effect, respectively. When the grooming behavior
      inducing effect of ACTH-(1-24) was abolished, either by the prior manipulation of
      central dopaminergic neurotransmission by the i.c.v. administration of the
      dopamine receptor antagonist, haloperidol, or, due to the occurrence of single
      dose tolerance to ACTH-(1-24), the pressor response was abolished as well. These
      data are in support of the postulate that the incidence of grooming behavior and
      the elevation of blood pressure are temporally associated and indicate that the
      two phenomena are causally related.

PMID- 8131055
TI  - Decreased forebrain [35S]TBPS binding and increased [3H]muscimol binding in rats
      that do not develop stress-induced behavioral depression.
AB  - Recent evidence suggests that anxiety and its biological concomitants may be
      involved in the pathophysiology of depression. In the present study, the in vitro
      radioligand binding of [3H]flunitrazepam, [3H]muscimol and [35S]t
      butylbicyclophosphorothionate (TBPS) sites on the benzodiazepine/GABA chloride
      ionophore receptor complex (BGRC) was examined using the learned helplessness
      paradigm. Only rats which did not develop the syndrome showed a significant
      increase in [3H]muscimol binding in cerebral cortex and a decrease in [35S]TBPS
      binding in cerebral cortex and hippocampus in comparison to naive controls. For
      both ligands, this represented a change in Bmax rather than a change in affinity.
      Adrenalectomy had no impact on these alterations indicating that critical
      endogenous factors are not manufactured by the adrenal glands. These findings
      suggest that the BGRC in the forebrain may be a site mediating the 'coping'
      ability of rats that do not develop the learned helplessness syndrome. The
      possible involvement of neurosteroids in this effect is discussed.

PMID- 8131057
TI  - The medial and lateral cell groups of the sexually dimorphic area of the gerbil
      hypothalamus are essential for male sex behavior and act via separate pathways.
AB  - Male reptiles, birds and mammals do not copulate if the medial preoptic area
      (MPOA) is destroyed but the MPOA cell groups necessary for male sexual behavior
      were not known. Here, two cell groups essential for copulation are identified in
      the sexually dimorphic area (SDA) of the gerbil (Meriones unguiculatus) MPOA.
      Bilateral cell-body lesions of either the medial or lateral SDA eliminated mating
      in sexually experienced male gerbils given testosterone. Nearby MPOA lesions did
      not. The medial and lateral SDA affect sex behavior via separate pathways since
      lesioning the medial SDA on one side of the brain and the lateral SDA on the
      other did not stop sexual behavior.

PMID- 8131056
TI  - Flumazenil induces localised increases in glucose utilization during diazepam
      withdrawal in rats.
AB  - The quantitative [14C]2-deoxyglucose autoradiographic technique has been employed
      to identify the neural circuits involved in diazepam withdrawal. Local cerebral
      glucose utilization (LCGU) was assessed in parallel groups of rats chronically
      treated with diazepam (5 mg/kg i.p., daily for 28 days), in rats that were
      withdrawn from chronic diazepam 24 h previously and in those that received
      flumazenil (5 mg/kg i.v.) immediately or 24 h after the last dose of diazepam.
      Two further groups received chronic vehicle or acute flumazenil (5 mg/kg i.v.).
      Rats withdrawn from diazepam 24 h previously did not produce changes in LCGU in
      the 51 structures examined compared with both control and chronic diazepam
      treated groups, suggesting that spontaneous withdrawal from small doses of
      diazepam does not evoke marked alterations in functional activity. In contrast,
      flumazenil-precipitated diazepam withdrawal produced a marked increase in glucose
      use in structures of the Papez circuit of emotion (mammillary body, anterior
      thalamus, cingulate cortex), together with increases in the septal nucleus,
      basolateral amygdala and nucleus accumbens. Less widespread increases in glucose
      use occurred in primary auditory and visual areas and in extrapyramidal areas.
      This pattern resembles that produced after acute FG-7142 administration (Brain
      Res., 475 (1988) 218-231). In rats receiving flumazenil 24 h after the last dose
      of diazepam there was a similar, but more restricted, pattern of change in LCGU.
      Flumazenil had no effect on LCGU in drug naive rats. Thus, flumazenil could only
      exert an effect upon LCGU in rats chronically treated with diazepam. These data
      provide functional neuroanatomical evidence for a withdrawal shift in the inverse
      agonist direction after chronic diazepam and suggest that flumazenil-precipitated
      withdrawal changes may merely be a reflection of this phenomenon.

PMID- 8131058
TI  - Estrogen-receptor immunoreactivity in hamster brain: preoptic area, hypothalamus
      and amygdala.
AB  - The distribution of estrogen-receptor containing cells in the preoptic area,
      hypothalamus and amygdala of female Syrian hamster brain was studied by
      immunocytochemical methods. Dense populations of estrogen-receptor immunoreactive
      (ER-IR) cells were found in the medial preoptic area, the bed nucleus of the
      stria terminalis, amygdala, ventral and lateral parts of the hypothalamus, and
      the arcuate nucleus. Injection of estradiol caused a decrease in estrogen
      receptor immunoreactivity (ERIR) containing cells within one hour, a decrease
      that may reflect a change in the ability of the occupied estrogen receptor to
      bind the particular antibody (H222) used rather than down-regulation of the
      estrogen receptor. Our findings on the distribution of estrogen-receptor
      containing cells in these areas using an immunocytochemical technique are
      consistent with and extend the findings of others using autoradiographic and in
      vitro binding techniques to study estrogen receptor distribution in hamster
      brain.

PMID- 8131059
TI  - Induction of arousal in hibernating European hamsters (Cricetus cricetus L.) by
      vasopressin infusion in the lateral septum.
AB  - Vasopressin immunostaining in the lateral septum of the European hamster
      (Cricetus cricetus L.) disappears in autumn, at the time of the first appearance
      of hypothermic periods characteristic to hibernation. Previous results have shown
      that chronic administration of vasopressin in the lateral septum during winter
      prevents the expression of hypothermic periods, suggesting a role for this
      peptide in hibernation. It is now observed that acute infusion of vasopressin,
      and in 50% of the cases, of a specific vasopressin V1 receptor agonist, during a
      hypothermic period results in an immediate termination of hypothermia. Infusion
      of oxytocin or a vasopressin V2 receptor agonist were without effect. The results
      indicate that the seasonal variation in central vasopressin activity, possibly
      through an interaction with V1 receptors, may play an important role in the
      expression of hibernation in the European hamster.

PMID- 8131060
TI  - Hippocampal EEG responses induced by carbachol and atropine infusions into the
      septum and the hippocampus in the urethane-anaesthetized rat.
AB  - Infusion of 1 microgram of carbachol, a potent cholinergic agonist, into the
      lateral septum of the urethane-anaesthetized rat systematically caused the
      induction of clear-cut hippocampal theta (theta). However, infusion of an
      equivalent amount of the drug into the hippocampus, close to the recording
      electrode, failed to induce theta in 50% of the animals and produced a mixture of
      theta waves and desynchronized activity, resulting in atypical EEG patterns, in
      the remaining subjects. Both carbachol EEG effects were blocked by intraseptal
      infusion of the antimuscarinic agent, atropine. Our data demonstrate that
      muscarinic receptors in the septum are predominant sites for cholinergic agonist
      antagonist action capable of generating or suppressing hippocampal theta in the
      rat. They also indicate that intraseptal cholinergic mechanisms play an important
      role in the initiation and generation of this rhythm.

PMID- 8131061
TI  - The effect of norbinaltorphimine, beta-funaltrexamine and naltrindole on NPY
      induced feeding.
AB  - The non-selective opioid receptor antagonist naloxone decreases the robust
      feeding observed after i.c.v. injection of neuropeptide Y (NPY). In the present
      study we evaluated the effects of three selective opioid receptor antagonists on
      NPY-induced feeding. Graded doses of norbinaltorphimine (norBNI), beta
      funaltrexamine (beta-FNA) and naltrindole (NTI), antagonists of the kappa, mu and
      delta receptors respectively, were preinjected (i.c.v.) in male rats prior to
      injection of 5 micrograms NPY (i.c.v.). Food intake was measured 1, 2 and 4 h
      post-NPY injection. Injection of beta-FNA and norBNI were most effective in
      reducing NPY-induced feeding, whereas NTI had little effect on NPY-induced
      feeding.

PMID- 8131062
TI  - Spread of epileptiform potentials in the neocortical slice: recordings with
      voltage-sensitive dyes.
AB  - The spread of epileptiform potentials in guinea pig neocortical slices was
      investigated by use of voltage sensitive dyes and a fast optical recording
      technique. Epileptiform activity was induced in a perfusion medium containing 10
      20 microM bicuculline-methiodide and by single pulse stimulation of layer I or
      the white matter. The location of minimal and maximal amplitudes, the shape of
      the potentials at specific sites and the velocity of spread were independent from
      the specific stimulation site. The expression of epileptiform activity appeared
      to depend on specific, possibly geometrical, properties of the tissue.

PMID- 8131063
TI  - Decreased activities of thiamine diphosphatase in frontal and temporal cortex in
      Alzheimer's disease.
AB  - Thiamine diphosphatase (TDPase) activity was measured using a colorimetric assay
      in frontal and temporal cortex obtained at autopsy from eight patients with
      neuropathologically confirmed Alzheimer's disease (AD) and from an equal number
      of control patients matched for age and autopsy delay interval, free from
      neurological or psychiatric disorders. TDPase activities were significantly
      reduced in frontal cortex (by 28%, P < 0.05) and temporal cortex (by 62%, P <
      0.01) of AD patients. These findings add to a growing body of evidence of altered
      thiamine neurochemistry in AD. Given the previous reports of an association of
      TDPase with cholinergic nerve terminals, loss of TDPase activities could reflect
      loss of cholinergic neurons in frontal and temporal cortex in AD.

PMID- 8131064
TI  - Ultrastructure of gamma-motoneurons after temporary or permanent interruption of
      peripheral target contact.
AB  - The paradigm of nerve crush, vs. nerve transection and ligation, was used to
      examine the effects of temporary or permanent interruption of peripheral target
      contact on the ultrastructure of cat thoracic gamma-motoneurons. The normal,
      highly ordered ultrastructure of Nissl bodies was lost 8 days after axotomy.
      Nissl bodies remained disorganised up to 305 days after nerve transection and
      ligation. In contrast, normal ultrastructural orderliness was restored for many
      of the Nissl bodies of gamma-motoneurons 64 days following nerve crush. A
      decrease in the area of the Golgi apparatus was found 64 days following both
      nerve crush and nerve transection with ligation. Other organelles were unaltered.

PMID- 8131065
TI  - Cerebrospinal fluid (CSF) extracted immediately after REM sleep deprivation
      prevents REM rebound and contains vasoactive intestinal peptide (VIP).
AB  - Intraventricular administration of cerebrospinal fluid (CSF) obtained from sleep
      deprived (SD) animals and vasoactive intestinal peptide (VIP) have been shown to
      increase rapid eye movement (REM) sleep. It has thus been suggested that VIP may
      accumulate in the CSF as a consequence of waking, and might thus be partly
      responsible for the subsequent rebound of REM sleep which follows prolonged
      wakefulness. To this data there are no studies testing this hypothesis. The
      purpose of this study, therefore, was to determine REM rebound following the
      extraction of CSF immediately after REMSD and to quantify by radioimmunoassay
      (RIA) the concentration of VIP in the CSF of progressively increasing REMSD
      periods. The results showed that REM rebound normally seen following REMSD is
      reduced by extraction of CSF, and that VIP concentration in such CSF is
      augmented. The results are discussed in terms of the possibility that waking
      induces an accumulation of VIP in the CSF, which is in turn involved in the
      production of REM sleep.

PMID- 8131066
TI  - Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and
      heterologous desensitization.
AB  - The effect of myo-inositol was examined on 5-HT2 receptor mediated facilitation
      of NMDA depolarization of rat neocortical neurons in vitro. Myo-inositol (1-10
      mM) potentiated the 5-HT facilitation, the potentiation increasing linearly with
      log 5-HT concentration. Myo-inositol also eliminated 5-HT induced heterologous
      desensitization of muscarinic and alpha 1-adrenergic receptor mediated
      facilitation. Our findings suggest that 5-HT induced homologous and heterologous
      desensitization results in part from depleting phosphoinositide substrate.

PMID- 8131067
TI  - Hypothermia decreases astroglial injury and arachidonate release during combined
      glucose-oxygen deprivation.
AB  - Hypothermia provides significant protection when initiated during or after
      cerebral ischemia in vivo. However, the mechanisms producing this protective
      effect are not known. Astroglial cultures were prelabeled with [3H]arachidonic
      acid. Hypothermia reduced both cellular injury and release of [3H]-labeled
      arachidonic acid metabolites during combined glucose-oxygen deprivation.
      Inhibition of phospholipid degradation may be one of the mechanisms that
      contributes to the protective effect of hypothermia.

PMID- 8131068
TI  - Comparative fractal analysis of cultured glia derived from optic nerve and brain
      demonstrate different rates of morphological differentiation.
AB  - O-2A progenitor cells derived from neonatal rat cerebral hemispheres or optic
      nerves, were induced to differentiate in culture into either oligodendrocytes or
      type 2 astrocytes. The fractal dimensions, a measure of morphological complexity,
      of the differentiating glial cells were measured over time. Analysis of the
      changes in fractal dimension (D) with respect to time revealed specific rates of
      growth for each glial phenotype and a specific final D. The time course of these
      changes is well fit by a simple mathematical model. While brain-derived
      oligodendrocytes matured faster than the astrocytes, they ultimately attained
      comparable levels of complexity, with similar maximum fractal dimensions.
      Oligodendrocytes from nerve also matured faster than nerve derived astrocytes, in
      contrast, however, they attained a greater morphological complexity than nerve
      astrocytes. While the brain-derived oligodendrocytes showed a faster rate of
      maturation than their optic nerve counterparts, astrocytes from both regions had
      similar rates of morphological differentiation. Self-similarity, a defining
      property of fractal objects was investigated, by determining the fractal
      dimension of cells over a range of magnifications. The calculated fractal
      dimension remained constant over a 10-fold range in optical magnification,
      illustrating that cultured glial cells exhibit this important characteristic of
      fractal objects. In addition, we analyzed the branching patterns of glial
      processes by the Sholl method and found that the results were not as
      interpretable or meaningful as those of fractal analysis.

PMID- 8131069
TI  - Subcellular localization of the inositol 1,4,5-trisphosphate receptor, P400, in
      the vestibular complex and dorsal cochlear nucleus of the rat.
AB  - The subcellular localization of the inositol 1,4,5-trisphosphate receptor
      protein, P400, was studied in the vestibular complex, an area to which Purkinje
      cells project, as well as in neurons of the dorsal cochlear nucleus and in
      ectopic Purkinje cells of adult rat brain. The receptor was demonstrated by
      electron microscopical immunocytochemistry using the avidin-biotin peroxidase
      complex procedure, with the monoclonal antibody 4C11 raised against mouse
      cerebellar inositol 1,4,5-trisphosphate receptor protein. Immunoreactivity was
      found in preterminal fibres and terminal boutons in the nuclei of the vestibular
      complex, generally associated with the subsurface systems and stacks or fragments
      of smooth endoplasmic reticulum. Ectopic Purkinje cells and cartwheel cells of
      the dorsal cochlear nucleus also displayed immunoreactivity, but this was much
      less intense in the latter. The results of the present study suggest that this
      receptor protein, involved in the release of Ca2+, is located in sites that
      enable it to influence the synthesis, transport and release of neurotransmitters.

PMID- 8131070
TI  - Propagation of hippocampal seizure activity arising from the hippocampus: a local
      cerebral blood flow study.
AB  - We studied the propagation of spike discharges and the changes in local cerebral
      blood flow (LCBF) by means of the electroencephalogram (EEG) and autoradiographs
      to elucidate the underlying mechanism and the propagation pathway in rats with
      limbic seizures. Seizures were induced by the unilateral microinjection of kainic
      acid (KA) into the dorsal hippocampus during which behavioral, EEG and LCBF
      changes were documented. Overall, the results indicate an initial spreading to
      the contralateral hippocampus from the ipsilateral hippocampus, followed by
      activation of the ipsilateral amygdala, other limbic structures, striatum and
      sensorimotor cortex. Finally, seizure activity spreads to the ipsilateral globus
      pallidus, substantia nigra, subthalamic nucleus, thalamus, septum and parietal
      cortex. The activation of the contralateral hippocampus in the KA model studied
      here occurs earlier than in the acute amygdaloid seizure model. Elucidation of
      the mechanisms underlying this difference in the propagation pathway will require
      the application in parallel of techniques examining these and other aspects of
      seizure activity.

PMID- 8131071
TI  - The nature of conditioned anti-analgesia: spinal cord opiate and anti-opiate
      neurochemistry.
AB  - The central nervous system contains circuitry that inhibits pain sensitivity
      (analgesia), as well as circuitry that opposes pain inhibition (anti-analgesia).
      Activation of analgesia systems and anti-analgesia systems can each be brought
      under environmental control using classical conditioning procedures. Analgesia
      can be produced by cues present before and during aversive events such as
      electric shock, while active inhibition of analgesia comes to be produced by cues
      never present immediately before or during shock and therefore signal safety. We
      have recently reported that these analgesia and anti-analgesia systems interact
      at the level of the spinal cord. A series of 3 experiments were performed to
      examine how such interactions occur. First, potential opioid mediation of
      conditioned analgesia was investigated using systemic and intrathecal (i.t.)
      delivery of opiate antagonists. Conditioned analgesia was found to be mediated by
      activation of spinal mu and delta opiate receptors. Second, analgesia produced by
      each of these receptor subtypes was challenged by environmental signals for
      safety. Analgesias produced by mu and delta opiate agonists were each abolished
      by safety signals. Third, antagonists/antisera directed against several putative
      anti-opiate neurotransmitters were tested i.t. to identify which mediate
      conditioned anti-analgesia at the level of the spinal cord. A cholecystokinin
      antagonist abolished conditioned anti-analgesia. In contrast, neuropeptide FF
      antiserum and a kappa opiate antagonist were without effect.

PMID- 8131072
TI  - Monosynaptic excitation of preganglionic vasomotor neurons by subretrofacial
      neurons of the rostral ventrolateral medulla.
AB  - Extracellular single unit recordings were made from barosensitive neurons in the
      subretrofacial nucleus (SRF) of the rostral ventrolateral medulla in chloralose
      anaesthetised cats. At the same time, single preganglionic neuron activity was
      recorded from filaments of the cervical sympathetic trunk (CST); barosensitive
      units were selected for study. Evidence for monosynaptic connections between the
      two neuron groups was sought by cross-correlation analysis of their ongoing
      activity. Cross-correlograms of 16/16 SRF/CST neuron pairs showed a broad peak
      (100-200ms wide), reflecting the synchronizing action of arterial baroreceptors
      on both neurons' activity. Two of the 16 cross-correlograms additionally showed a
      robust, statistically significant, narrow peak of a single 2 ms bin width,
      providing the first physiological demonstration that ventrolateral medullary
      neurons monosynaptically excite preganglionic sympathetic neurons. Deductions are
      made about the strength, convergence and divergence of the connection.

PMID- 8131073
TI  - Induction of 27-kDa heat shock protein following cerebral ischemia in a rat model
      of ischemic tolerance.
AB  - Preconditioning the brain with sublethal cerebral ischemia induces tolerance to
      subsequent lethal periods of ischemia (ischemic tolerance). The purpose of this
      study is to investigate the role of low-molecular weight stress proteins, 27-kDa
      heat shock protein (HSP27) and alpha B crystallin, in ischemic tolerance. We
      measured the content of these proteins with enzyme immunoassay in the rat
      hippocampus and cerebral cortex following 6 min of ischemia with and without
      preconditioning with 3 min of ischemia and 3 days of reperfusion. We also
      visualized the localization of HSP27 immunohistochemically in comparison with
      that of HSP70. A 3-min period of ischemia caused a 2.4-fold increase in HSP27
      content in the hippocampus after 3 days. Immunohistochemical localization of
      HSP27 was found in glial cells in all subregions of the hippocampus, whereas
      HSP70 immunostaining was seen only in CA1 pyramidal neurons. HSP27 content in the
      hippocampus decreased 2 h after 6 min of ischemia. HSP27 content progressively
      increased in the unpreconditioned hippocampus after 1 and 3 days, but returned to
      preischemic levels in the preconditioned hippocampus. HSP27 and HSP70
      immunostaining was seen in CA1 pyramidal neurons after 1 day both with and
      without preconditioning. After 3 and 7 days, an intense HSP27 staining was
      observed in reactive glial cells in the CA1 without preconditioning, whereas the
      staining decreased in the preconditioned hippocampus. HSP70 staining was seen
      only in neurons at these time points. We observed no significant changes in HSP27
      content in the cerebral cortex although neurons in the third and fifth layers
      were immunostained after 1 and 3 days. We observed no alterations in alpha B
      crystallin content after ischemia both in the hippocampus and the cortex. The
      present study demonstrated that cerebral ischemia induces HSP27 expression but
      not alpha B crystallin. Both HSP27 and HSP70 induction had a good temporal
      correlation with the induction of ischemic tolerance. However, different sites of
      action were suggested because the localization and cell types of HSP27 induction
      were quite different from those of HSP70 induction. The result suggests that it
      is unlikely that HSP27 is directly involved in the protection afforded by
      ischemic preconditioning.

PMID- 8131074
TI  - Hippocampal kindling protects several structures from the neuronal damage
      resulting from kainic acid-induced status epilepticus.
AB  - In an attempt to study the effects of piriform cortex damage on kindled seizure
      propagation, we administered kainic acid (12 mg/kg; i.p.) to rats previously
      kindled from the dorsal hippocampus. Unexpectedly, the ensuing status epilepticus
      (SE) in the kindled rats did not result in the piriform cortex damage normally
      observed in naive rats. As a result of this surprising finding, a more
      comprehensive investigation was undertaken to compare dorsal hippocampal kindled
      and control rats on their electrographic and behavioral SE development and
      subsequent brain damage. The SE induction profile and the pattern of brain damage
      observed in our control rats was similar to previous reports [Neuroscience, 14
      (1985) 375-403; Brain Res., 218 (1981) 299-318]. By contrast, although fewer
      kindled rats than controls responded to the initial dose of kainic acid with
      electrographic and behavioral seizures, those many kindled rats that did respond,
      showed a pattern of SE induction that was different from controls. Kindled rats
      manifested fewer 'wet dog shakes', more generalized convulsions and a faster
      development of severe limbic status (SLS) than controls. In addition, without
      pharmacological intervention, the SLS continued longer in kindled rats than in
      controls. Histological examination revealed brain damage in kindled rats that was
      markedly different from controls. Unlike controls, kindled rats had no damage in
      the piriform cortex or substantia nigra reticulata and minimal hippocampal
      damage, yet showed midline thalamic and anterior olfactory nuclei damage similar
      to controls. These differences were observed from 1 to 28 days after kindling.
      Although the mechanism(s) of this kindling-based neuroprotection is not known,
      its discovery should add importantly to our understanding of epilepsy-induced
      alterations of subsequent neuronal function.

PMID- 8131075
TI  - Immunohistochemical localization of Ca2+/calmodulin-dependent protein kinase II
      in the rat retina.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) consisting of alpha
      and beta isoforms is highly expressed in the central nervous system and is
      implicated in the regulation of various Ca(2+)-dependent physiological processes.
      We investigated the immunohistochemical distribution of the alpha and beta
      isoforms of this enzyme in the rat retina, using highly specific monoclonal
      antibodies which recognize each isoform. Immunoblotting revealed that not only
      the alpha but also the beta isoform of CaM kinase II were expressed in the
      retina. The immunohistochemical study showed that highly alpha-immunoreactive
      products were localized in amacrine cells in the inner nuclear layer and
      displaced amacrine cells and ganglion cells in the ganglion cell layer. In
      addition, two well-defined bands within the inner plexiform layer were densely
      stained with the anti-alpha antibody. By contrast, immunoreactivity against the
      anti-beta antibody was very weak in the same neuronal components of the retina.
      beta-Immunoreactive products were homogeneously distributed throughout the inner
      plexiform layer and no well-defined bands were detected in this layer. Glial
      cells such as Muller cells were immunoreactive neither to alpha nor beta
      antibody. A possible co-existence of choline acetyl transferase (ChAT) within CaM
      kinase II alpha-immunopositive neurons was examined by evaluating adjacent
      sections stained with anti-CaM kinase II alpha antibody and anti-ChAT antibody,
      respectively. The distribution of CaM kinase II alpha immunoreactivity in the rat
      retina was remarkably similar to that of ChAT immunoreactivity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8131076
TI  - Effects of prenatal cocaine exposure on the nigrostriatal dopamine system: an in
      vivo microdialysis study in the rat.
AB  - Pregnant rats were given injections of saline (0.5 ml/kg) or cocaine (10 mg/kg,
      20 mg/ml, s.c.) twice daily between gestational days 7-21. Offspring were
      examined by microdialysis between postnatal days 10-125 to study the effects of
      prenatal cocaine exposure on the nigrostriatal dopamine (DA) system. Twenty-min
      dialysis samples were collected and assayed for DA, DOPAC and HVA. After four
      baseline samples, the rat was exposed to 20 min of intermittent tail pinch and
      monitored for four samples; then each rat received an acute injection of cocaine
      (20 mg/kg, i.p.) and six additional samples were collected. Basal dialysate
      concentrations of all DA markers, estimated from pre-implantation calibration of
      the probes, were markedly reduced in young rats ('pups', 10-30 days old) as
      compared with adult rats (40-125 days old). Compared to control pups, basal DA,
      as well as DOPAC and HVA, were elevated in the prenatal-cocaine pups. Tail pinch
      (a mild stressor) produced a significant increase in DA only in the pups
      prenatally exposed to cocaine. The increase in basal DA induced by an acute
      cocaine injection (20 mg/kg) was also greater and more prolonged in the prenatal
      cocaine pups. In older rats (40-125 days) there were no group differences in any
      of the DA parameters. Thus prenatal exposure to cocaine produces an activation of
      the DA system which persists after birth but returns to normal in older rats.

PMID- 8131077
TI  - Real-time monitoring of endogenous noradrenaline release in rat brain slices
      using fast cyclic voltammetry: 3. Selective detection of noradrenaline efflux in
      the locus coeruleus.
AB  - Fast cyclic voltammetry (FCV) at carbon fibre microelectrodes was used to monitor
      'real time' endogenous noradrenaline (NA) efflux in superfused slices of rat
      locus coeruleus (LC) following local electrical stimulation. When stimulated with
      a standard train (30 pulses, 100 Hz, 0.2 ms, 10 mA, every 5 min), efflux of
      monoamine was constant over the experimental period (2.5 h): Amine efflux
      declined by only 16 +/- 5% while uptake half-life lengthened by only 9 +/- 8%.
      When calibrated in solutions of NA, peak amine efflux corresponded to 0.31 +/-
      0.04 microM (mean +/- S.E.M., n = 28) and was removed by uptake with a half-life
      of 2.93 +/- 0.28 s (n = 16). The released compound was confirmed as NA on the
      basis of pharmacological and electrochemical criteria. Stimulated monoamine
      efflux was reversibly reduced by 78% by omission of Ca2+ from the superfusate for
      30 min (P < 0.05). Ro 4-1284 (1 microM), a fast-acting reserpine-like drug,
      decreased amine efflux by 86% (P < 0.05). The monoamine oxidase inhibitor
      pargyline (2 microM) increased efflux by 30% (P < 0.05). Desipramine (0.05
      microM), a selective NA uptake blocker, significantly increased amine efflux (by
      96%, P < 0.05) and uptake half-life (by 314%, P < 0.05). Fluvoxamine (0.5
      microM), the selective serotonin (5HT) uptake blocker, increased efflux by 59% (P
      < 0.05) and the uptake half-life by 122% (P < 0.05). Vanoxerine (GBR 12909: 0.3
      microM), the dopamine (DA) uptake blocker, had no effect on amine efflux or
      uptake half-life. The voltammogram of the released amine had single oxidation and
      reduction peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131078
TI  - Chronic exposure to alcohol during development alters the calcium currents of
      cultured cerebellar Purkinje neurons.
AB  - The effect of chronic exposure to alcohol during development on the calcium
      currents of rat cerebellar Purkinje neurons was studied in a culture model system
      using voltage clamp techniques. The neurons were exposed to 30 mM alcohol
      (ethanol) during the main period of morphological and physiological development.
      The calcium currents were measured at the end of the treatment period, which
      lasted for 8-10 days. The currents were evoked by a series of depolarizing test
      commands from holding potentials of -62 mV and -90 mV. The evoked currents were
      qualitatively similar in control and alcohol-treated neurons and were comprised
      of a high threshold slowly inactivating calcium current and a low threshold
      rapidly inactivating calcium current. The low threshold current could be observed
      in isolation at test potentials ranging from -50 to -30 mV. The mean peak
      amplitude of this current was significantly smaller in the alcohol-treated
      neurons compared to controls. At more depolarized test potentials, the high
      threshold current dominated the current response, which was characterized by an
      initial peak that slowly declined to a smaller relatively sustained level. The
      mean amplitude of the high threshold current at both peak and sustained levels
      was significantly larger in the alcohol-treated neurons compared to controls.
      Measurement of cell size indicated that alcohol-treated neurons were
      approximately 25% smaller than control neurons, a difference that could
      contribute to the smaller low threshold current observed in these neurons. These
      data show that chronic exposure to alcohol during the development can
      significantly influence the amplitude of calcium currents of the cultured
      Purkinje neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131079
TI  - Distribution of free D-serine in vertebrate brains.
AB  - Free D-serine distribution in vertebrate brains was investigated. In various
      brain regions of the lower vertebrate species, carp, frog and chick, free D
      serine levels were low. On the contrary, in the mammals, mouse, rat and bull, the
      contents of free D-serine were high in the forebrain (around 400 nmol/g wet
      weight, and the ratio of D-serine to L-serine, was D/L = 0.4), and low in the
      hindbrain. In developing mice, D-serine levels in the cerebrum increased with age
      and attained the adult level (D/L = 0.40) 8 weeks after birth. In the cerebellum
      and brain stem, the free D-serine levels increased with age until 2 weeks,
      followed by a decrease to the adult levels: the D/L ratios remained constant
      until 2 weeks of age, then decreased to 0.03 in the cerebellum and 0.12 in the
      brain stem. Free D-serine was shown not to be of microbial origin using germ-free
      mice. In the rat forebrain, D-serine was evenly distributed in two cerebral
      regions, namely frontal and occipital lobes. The D/L ratios in other regions of
      forebrain, hippocampus and hypothalamus, were comparable to the cerebrum (D/L =
      0.4), while that in the olfactory bulb was lower (D/L = 0.12). In the rat
      cerebrum, the D-serine content in the grey matter was significantly higher than
      that in the white matter. The contents of free D-serine in bovine cerebrum and
      cerebellum were similar to those in other mammalian brains, but the D/L ratio for
      bovine cerebral grey matter was lower than that for the cerebral white
      matter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131080
TI  - Coexistence of the stigmoid body and estrogen receptor in some neuronal groups
      involved in rat reproductive functions.
AB  - Recent immunohistochemical studies have suggested that the forebrain distribution
      of stigmoid bodies, marked by an antibody against placental aromatase-associated
      antigen X-P2 (PAX), overlaps with that of the common binding sites of androgen
      and estrogen. In the present light- and electron-microscopy study the coexistence
      of stigmoid bodies and estrogen receptors (EsR) is immunohistochemically examined
      and quantitatively analyzed in the medial preoptic region, part of the bed
      nucleus of the stria terminalis and part of the medial amygdaloid nucleus of
      young female rats. Light microscopy with double immunostaining for PAX and EsR in
      all three regions indicates that 75-84% of the total of PAX-immunoreactive
      stigmoid structures are present in neurons which also contain EsR-immunoreactive
      nuclei, and that 75-78% of EsR-immunoreactive neurons contain PAX-immunoreactive
      inclusions. Electron microscopic analysis confirms that 70-80% of stigmoid body
      containing neurons have EsR-immunoreactive nuclei. These results indicate that
      the majority of the stigmoid bodies and EsRs intimately coexist, strongly
      suggesting a functional interrelationship in brain regions which are involved in
      rat reproductive functions. Stigmoid bodies may play a role in subneuronal EsR
      mechanisms associated with aromatization in these sex steroid targets in rat
      brain.

PMID- 8131081
TI  - Immunohistochemical demonstration of tissue kallikrein in the neurons of rat
      brain.
AB  - The distribution of tissue kallikrein (EC.3.4.21.35) in the rat brain was
      investigated by an enzyme-linked immunosorbent assay (ELISA) and
      immunohistochemical technique using antiserum against rat urinary kallikrein.
      More than 75% of the total amount of kallikrein in the extracts of the cerebral
      cortex and brain stem was determined by the ELISA to be in the form of
      prokallikrein, suggesting that the greater part of the enzyme exists in the form
      of pro-enzyme in the central nervous system. Furthermore, immunohistochemical
      examination revealed that, although the kallikrein-positive cells were widespread
      and scattered in the brain, the immunoreactive substances preferentially locate
      in the neuronal cell bodies and their processes in both the cerebral cortex and
      brainstem.

PMID- 8131082
TI  - Interaction between enkephalin and GABA in the chicken retina: further analyses
      of coexisting relationships.
AB  - Previous studies have indicated an interactive relationship between enkephalin
      and gamma-aminobutyric acid (GABA) in the vertebrate retina. Among these studies
      are those that have demonstrated the colocalization of enkephalin and GABA in
      retinal amacrine cells. In the present study, enkephalin immunocytochemistry was
      combined with either autoradiography of tritiated GABA high-affinity uptake or
      GABA immunocytochemistry to further investigate the coexistence of GABA in
      enkephalin-amacrine cells of the chicken retina. A regional analysis revealed
      that the percentage colocalization of GABA high-affinity uptake in enkephalin
      amacrine cells did not vary appreciably throughout the retina. Overall, 15.2% of
      enkephalin-amacrine cells exhibited high-affinity GABA uptake. Double-label
      immunofluorescence histochemistry revealed that 15.1% of enkephalin-amacrine
      cells express endogenous GABA-like immunoreactivity. These double-labelled cells
      were observed throughout central and peripheral regions of the retina. In each of
      the double-label analyses, only less intensely labelled enkephalin-amacrine cells
      expressed markers of GABA activity. The two double-label analyses reveal almost
      identical percentages of coexistence of GABA markers in chicken enkephalin
      amacrine cells and therefore, provide supportive evidence for the GABAergic
      nature of these cells. These results suggest a functional diversity in the
      population of chicken enkephalin-amacrine cells and imply the possibility of
      multiple signalling through amacrine cells which contain enkephalin and GABA.

PMID- 8131083
TI  - Effects of taurine on basal and stimulated luteinizing hormone (LH) and LH
      releasing hormone secretion in ovariectomized rats: in vitro studies.
AB  - Taurine (Tau), a putative inhibitory amino acid neurotransmitter, has been shown
      to inhibit luteinizing hormone (LH) release in vivo. We investigated the effect
      of this amino acid on LH secretion by cultured anterior pituitary cells. A 5-h
      incubation with Tau (10(-3)-10(-8) M) did not affect basal or LH-releasing
      hormone (LHRH)-stimulated LH release. Basal LHRH release from superfused
      mediobasal hypothalamic fragments was not affected by Tau (10(-3) M). However,
      this substance clearly diminished LHRH release after stimulation with KCl (50 mM)
      or N-methyl-D-aspartate (10(-4) M). It is concluded that Tau may exert an
      inhibitory effect on LH secretion acting at the hypothalamic level.

PMID- 8131084
TI  - Synaptophysin and chromogranin A immunoreactivities of Lewy bodies in Parkinson's
      disease brains.
AB  - Lewy bodies commonly observed in brains with Parkinson's disease (PD)
      histochemically contain both protein and lipid as chemical components.
      Ultrastructurally, they are composed of filamentous, vesicular and granular
      structures. We investigated PD brains with light and electron microscopic
      immunohistochemistry using antibodies against two marker proteins for neuronal
      secretory vesicles, synaptophysin and chromogranin A. Both antibodies
      immunolabeled the peripheral zones and occasionally central cores of Lewy bodies
      of the classical and intraneuritic types. In addition, the diffuse immunolabeling
      was observed in Lewy bodies of the cortical type. Furthermore, the
      ultrastructural immuno-decoration was found mainly in the vesicular structures,
      and also in the filamentous and granular structures of Lewy bodies. Immuno-blot
      analysis of each antibody showed no difference between PD and normal control
      brains. The present observations suggest that vesicular profiles of Lewy bodies
      represent presynaptic and dense core secretory vesicles, and therefore that the
      lipid elements of Lewy bodies are derived from membrane lipids of these vesicles.

PMID- 8131085
TI  - Does bicuculline antagonize NMDA receptors? Further evidence in the rat striatum.
AB  - In two areas of the rat striatum, the in vitro N-methyl-D-aspartate (NMDA, 50
      microM)-evoked release of [3H]dopamine was studied in the presence of bicuculline
      (5 and 50 microM), an antagonist of GABAA receptors. The responses observed with
      the higher concentration (50 microM) is compatible with an antagonistic activity
      of bicuculline on NMDA receptor, as recently reported by Wright and Nowak.

PMID- 8131086
TI  - Suppression of hippocampal synaptic transmission by the spider toxin omega
      agatoxin-IV-A.
AB  - Effects of omega-agatoxin-IV-A (AGTX) on synaptic transmissions were examined in
      thin transverse sections of the guinea pig hippocampus. AGTX suppressed, in a
      dose-dependent manner, field potentials elicited by mossy fiber stimulation in
      CA3 pyramidal cell layer. AGTX also suppressed field potentials elicited by
      perforant fiber stimulation in granular layer without marked changes in
      antidromic responses. These results suggest that Ca2+ entry into presynaptic
      terminals via P-like calcium channels is at least partly responsible for release
      of glutamate.

PMID- 8131087
TI  - A subpopulation of olivocerebellar projection neurons express neuropeptide Y.
AB  - By neuropeptide Y (NPY) immunohistochemistry and in situ hybridization
      histochemistry with digoxigenin-labeled oligonucleotide probes for this peptide,
      a subpopulation of neurons in the caudal portions of the rat dorsal and medial
      accessory olives were found to express NPY immunoreactivity and mRNA. In the
      cerebellum, NPY-immunolabeled climbing fibers were distributed to the flocculus
      and parts of vermal cortex. The results suggest particular association of NPY
      with the climbing fiber system presumably mediating spinal, visual and vestibular
      inputs.

PMID- 8131088
TI  - Radiolabeled antibody imaging of patients with potentially resectable colorectal
      adenocarcinoma.
AB  - Thirty-two patients with potentially resectable recurrent colorectal
      adenocarcinoma were imaged with the radioimmunoconjugate 111In-satumomab
      pendetide to determine whether imaging supplies clinically relevant information
      relating to the extent of disease in patients with different presenting
      characteristics. Patients included 12 with increasing carcinoembryonic antigen
      (CEA) without anatomical evidence of recurrence, 13 with radiological
      abnormalities consistent with apparently isolated metastases, and 7 with
      recurrence and anatomical abnormalities of unclear significance. 111In-satumomab
      pendetide imaging detected extrahepatic abdominal and pelvic disease in 16
      subjects. Imaging was most informative in patients with recurrent disease and
      anatomical abnormalities of unclear significance, but imaging of the liver was
      suboptimal owing to high levels of nonspecific uptake. We conclude 111In
      satumomab pendetide imaging can supply clinically relevant information relating
      to the extent and location of recurrent colorectal adenocarcinoma in patients
      with extrahepatic abdominal and pelvic radiological abnormalities of unclear
      significance and in radiologically normal patients with high CEA levels.

PMID- 8131089
TI  - Expression of multiple oncogenes in human esophageal carcinomas.
AB  - To study the oncogenesis of human esophageal carcinoma, the expression of a
      variety of oncogenes was studied in 10 esophageal carcinoma cell lines and 16
      pairs of tumor and nontumor tissues removed from patients with esophageal
      carcinoma. Northern blot analyses using 11 different oncogene probes revealed
      that 5 oncogenes, i.e. c-myc, c-H-ras, c-sis, c-raf, and c-fos, were expressed.
      Among them, a variant c-sis mRNA transcript of 2.7 kilobase (kb) was expressed in
      7 of 10 cell lines and in 9 of 16 tumor tissues. Furthermore, an overexpression
      and an amplification of c-myc gene was observed in some cell lines. These results
      suggest that multiple oncogene expression may be required for the induction,
      maintenance, and progression of esophageal carcinoma. The expression of a 2.7-kb
      transcript, of c-sis and overexpression of c-myc gene may play some role in the
      carcinogenesis of esophageal carcinoma.

PMID- 8131090
TI  - 3H-NECA binding to polymorphonuclear membrane: effect of sera from patients with
      Hodgkin's disease.
AB  - Several studies have shown that sera from patients with Hodgkin's disease contain
      factors capable of inhibiting polymorphonuclear functions, among them chemotaxis.
      In the present study, we investigated whether these sera, which were able to
      inhibit PMN chemotaxis in the agarose test, were also able to affect the 3H-NECA
      binding to PMN membrane obtained from healthy donors. Control experiments were
      carried out using PMN incubated with a pool of sera from healthy volunteers. No
      significant difference was found in the maximum number of binding sites; on the
      contrary, the equilibrium dissociation constant was significantly increased in
      the membrane preparation of PMN incubated with pathological serum.

PMID- 8131091
TI  - Chemotherapy for angiosarcoma of the breast: case report of 30-year survival and
      analysis of the literature.
AB  - Angiosarcoma of the breast is a rare and highly malignant neoplasm with few long
      term survivors. Little is known about the effects of chemotherapy for patients
      with disseminated disease or its role in the adjuvant setting. We report the case
      of a patient with metastatic angiosarcoma of the breast who achieved a long-term
      clinical and pathological remission after treatment with methotrexate. The 30
      year course of her disease is the longest reported survival with documented
      metastatic angiosarcoma of the breast. Analysis of the role of chemotherapy in
      the adjuvant setting and its effects in relation to histological subtype is
      undertaken. Adjuvant chemotherapy for patients with poorly differentiated
      angiosarcoma of the breast results in a higher proportion of patients relapse
      free (29.2%) compared to patients not receiving adjuvant chemotherapy (4.4%) (p <
      0.05). Patients with well-differentiated tumors do not appear to derive benefit
      from adjuvant chemotherapy. The effects for patients with disseminated disease
      are reported.

PMID- 8131092
TI  - Management of brain metastases.
AB  - Brain metastases usually develop in patients with disseminated systemic disease.
      Effective palliation is available for the vast majority of patients with brain
      metastases, but many will die within 6 months, usually from progressive systemic
      tumor. However, in a substantial proportion of patients, a vigorous therapeutic
      approach using surgery, radiotherapy, and possibly chemotherapy leads to years of
      productive life. Recurrent brain metastases can often be retreated using newer
      techniques of brachytherapy and stereotactic radiosurgery as well as conventional
      treatments. Brain metastases do not necessarily mean imminent death for every
      patient, and physicians can now offer patients a growing range of therapeutic
      options. Furthermore, attention to symptomatic therapies can improve the quality
      of life for all patients, even those whose survival will be relatively short.

PMID- 8131093
TI  - Pelvic exenteration for recurrent colorectal carcinoma: a review.
AB  - Pelvic recurrence following curative resection for colorectal carcinoma continues
      to pose a challenge to the oncologist despite current multimodality therapy.
      Pelvic exenteration with or without sacral resection may provide long-term
      disease-free survival and a chance of cure for a small subset of patients in whom
      the recurrent disease is confined to the pelvis and can be resected with "clear"
      margins. For others with residual disease, exenteration may offer good palliation
      for the intractable symptoms, but no survival advantage. The clinical decision to
      perform exenteration with palliative intent must be individualized. This is
      generally not advised because of the short life expectancy in the face of
      prolonged convalescence. This technically demanding procedure is associated with
      significant morbidity, especially in patients with prior pelvic radiation.
      Current advances in urinary diversion and methods of pelvic reconstruction may
      significantly reduce these problems. The surgeon's experience and careful patient
      selection remain the most important determinants of success with this operation.

PMID- 8131094
TI  - Self-assembling drugs: a new approach to biochemical modulation in cancer
      chemotherapy.

PMID- 8131095
TI  - Transgenic mice as models for tumorigenesis.

PMID- 8131096
TI  - Asbestos and cancer: epidemiological and public health controversies.
AB  - This paper discusses many of the currently controversial issues surrounding
      asbestos health effects and their relationship to cancer risk assessment and risk
      management. The major conclusions reached from this analysis are: (1) All
      asbestos fiber types are carcinogenic and pose a threat to human health.
      Therefore, all fiber types should be regulated similarly. (2) The health risks
      associated with indoor asbestos exposure are uncertain. Available data show that
      some groups, such as building maintenance personnel (among others), may contract
      asbestos-related diseases secondary to indoor exposure. Clearly, additional
      research is needed to accurately determine the extent and nature of disease risk
      under these conditions. (3) Controlled use has proved an elusive goal. Limited
      information from underdeveloped countries parallels the experience of Western
      industrialized nations. Efforts by the Canadian government to establish markets
      for asbestos in these areas should be opposed. (4) Finally, asbestos-related
      cancer risk is no longer confined to asbestos industry workers. Asbestos-related
      mesothelioma has been documented in a wide variety of occupational and
      nonoccupational settings, highlighting the need for continued surveillance to
      minimize potential health risks.

PMID- 8131097
TI  - Health care: economic cancer.

PMID- 8131098
TI  - Choice and competition: a prescription for affordable health care reform.

PMID- 8131099
TI  - Health care reform in oncology.

PMID- 8131100
TI  - Single-payer health care reform: combining increased access and cost containment.

PMID- 8131101
TI  - Cultural barriers to health care reform.
AB  - The rate of proliferation of health care reform proposals makes it impossible to
      consider them all adequately; whatever plan is finally legislated, there will be
      many who are not satisfied with it, and clamor for change is likely to be a
      prominent feature of health care politics for a long time. This article takes a
      brief look at the health care reform process in the United States, including some
      of the impediments to development of a plan that would address both contemporary
      and future issues. Some traditional ethical viewpoints and cultural values,
      having to do with concepts of justice, are seen as inimical to long-range program
      development. The need for alteration of traditional views is regarded as urgent,
      to facilitate cultural movement in directions that will not only permit
      development of workable health care programs, but will extend broadly to address
      other compelling societal issues. The impetus for advantageous cultural movement
      originates among perceptive individuals who are regarded by society as
      legitimately influential. Many physicians still are accorded this sort of
      recognition, and the considered input of medical professionals is essential.

PMID- 8131102
TI  - Oncology issues in health care reform.

PMID- 8131103
TI  - Ways to reduce the cost of oncology care without compromising the quality.

PMID- 8131104
TI  - c-sis and oncogene expression: a fundamental approach toward understanding
      esophageal cancer.

PMID- 8131105
TI  - Editorial review of Dr. Darryl Rideout's article entitled "Self-assembling drugs:
      A new approach to biochemical modulation in cancer chemotherapy.

PMID- 8131106
TI  - Re: "We may be lost, but we're sure makin' good time".

PMID- 8131107
TI  - Cloning of a recA-like gene from the diazotroph Herbaspirillum seropedicae strain
      Z78.
AB  - A recombinant plasmid, pBMR5, carrying a recA-like gene of Herbaspirillum
      seropedicae, was isolated from a H. seropedicae genomic library by intergeneric
      complementation of Escherichia coli recA mutant strain HB101. Quantitative
      survival experiments showed that pBMR5 restored the ultraviolet radiation and
      methyl methanesulfonate resistances and recombinational proficiency of this
      strain. Hybridization studies showed that there is DNA sequence homology between
      the recA gene of E. coli K12 and that of H. seropedicae. Restriction sites for
      EcoRI, HindIII, BamHI, and Bg/II were found in the DNA insert derived from H.
      seropedicae in pBMR5. A Tn5 insertional mutant of pBMR5, called pBMR26.2, failed
      to restore recombination proficiency and methyl methanesulfonate and ultraviolet
      resistance to recA mutants of E. coli.

PMID- 8131108
TI  - Maintenance of infective Borrelia burgdorferi Sh-2-82 in 4% oxygen - 5% carbon
      dioxide in vitro.
AB  - The infectivity of Borrelia burgdorferi depends on the number of passages in
      Barbour-Stoenner-Kelly (BSK-II) medium in ambient air. In this study the
      parameters of medium formulation or O2-CO2 atmosphere were altered to define
      conditions that would retain borrelial infectivity upon serial passage. The
      infective strain Sh-2-82 was passaged 20 times in BSK-II and BSK-A (a modified
      BSK-II medium) in ambient O2-CO2 and BSK-II in 4% O2 - 5% CO2 - 91% N2.
      Spirochetes of every fifth passage were inoculated intraperitoneally into
      neonatal Lewis rats. Infectivity was lost after 15 passages in media in ambient
      O2-CO2. However, infectivity was maintained through all 20 passages in BSK-II in
      4% O2 - 5% CO2 - 91% N2. There were no pH differences, but the dissolved O2
      concentration in ambient O2-CO2 was approximately twice that in 4% O2 - 5% CO2 -
      91% N2. Therefore, differences in infectivity were due to culturing under a
      constant environment of decreased O2 and increased CO2. This environment may
      place a selective pressure on the borreliae for retention of the infective
      phenotype. The results suggest that the levels of O2 and CO2 in the environment
      influence infectivity by preventing the loss of genetic information or inducing
      the expression of virulence determinants in B. burgdorferi.

PMID- 8131109
TI  - Exogenous rh-urokinase modifies inflammation and Pseudomonas aeruginosa infection
      in a rat chronic pulmonary infection model.
AB  - The effect of recombinant human urokinase (rh-UK) in a rat model of chronic
      Pseudomonas aeruginosa pulmonary infection was studied. Efficacy was assessed by
      lung histology and quantitative bacteriology. Male Sprague-Dawley rats received 1
      x 10(4) or 1 x 10(5) P. aeruginosa encapsulated in agar beads via the
      intratracheal route on day 1. Intratracheal administration of up to 12,500 units
      of rh-UK on day 21 led to a dose-dependent disappearance of viable organisms from
      the lungs by day 24 in rats receiving 10(4) organisms. In slightly longer term
      infections (30 days), rh-UK was still effective in facilitating the disappearance
      of the organisms from the lungs of most of the treated animals. rh-UK was
      effective in eliminating organisms when animals were infected with 10(4), but not
      10(5) bacteria. In vitro analysis revealed that rh-UK was not directly toxic for
      the organisms. Histologically, lungs from short-term infected control animals
      exhibited acute inflammation, inflammatory cell infiltrates, and fibrin
      deposition. Histology of lungs from UK-treated, short-term infected rats revealed
      decreased airway inflammation and cellular infiltration compared with infected
      controls. Lungs from infected animals treated with 12,500 units of rh-UK were
      histologically indistinguishable from the lungs of uninfected control animals,
      except for the foreign body reaction. These results indicate that exogenous rh-UK
      may be efficacious in the treatment of pulmonary inflammation accompanying
      exposure to Gram-negative bacteria such as P. aeruginosa.

PMID- 8131110
TI  - The expression of potential colonization factors of yeasts isolated from fish
      during different growth conditions.
AB  - Three strains, Rhodotorula rubra, Rhodotorula glutinis, and Candida zeylanoides,
      isolated from fish, were tested for the expression of putative tissue
      colonization factors. All strains were able to bind collagen type I, fibronectin,
      and laminin to various degrees after growing on various solid and broth media,
      while the binding to collagen type IV was sparse under all conditions tested. For
      the three strains tested, a very low cell surface hydrophobicity was shown for
      growth on various solid and broth media. Mostly, the strains also expressed a
      negatively charged surface. Extracellular protease activity using different
      substrates was shown for all three strains. Furthermore, two properties related
      to iron scavenging, i.e., binding of lactoferrin and production of siderophores,
      were also tested. For the three strains a capacity to bind lactoferrin as well as
      a capacity to excrete siderophores were demonstrated. Since these different
      properties have been correlated to virulence and to the capacity of colonization
      in other organisms, we address the question of whether the expression of these
      properties in yeasts could contribute to colonization in fish.

PMID- 8131111
TI  - Dental care of AIDS patients.

PMID- 8131112
TI  - Bicycle helmets not the only answer.

PMID- 8131113
TI  - Punishing physicians for sexual infractions.

PMID- 8131114
TI  - Postdural puncture headache.

PMID- 8131115
TI  - Early warnings about smoking.

PMID- 8131116
TI  - Can't get away from Latin.

PMID- 8131117
TI  - Can't get away from Latin.

PMID- 8131118
TI  - Strengthening the foundation: the physician's vital role in primary health care
      in Canada.

PMID- 8131119
TI  - Should CMAJ publish a French edition?

PMID- 8131121
TI  - Criteria for labelling infant formulas as "hypoallergenic". Allergy Section,
      Canadian Pediatric Society.

PMID- 8131120
TI  - Periodic health examination, 1994 update: 1. Obesity in childhood. Canadian Task
      Force on the Periodic Health Examination.
AB  - OBJECTIVE: To update the 1979 Canadian Task Force on the Periodic Health
      Examination recommendation on screening for childhood obesity by reviewing any
      new evidence concerning health risks in childhood and adulthood, and effective
      preventive or therapeutic interventions. OPTIONS: Detection: routine measurement
      of height and weight, use of skinfold thickness measurements, calculation of body
      mass index (BMI). INTERVENTION: diet, exercise, behaviour modification and
      comprehensive family-based weight-reduction programs. Components of these
      interventions could be offered routinely or reserved for children and families
      who perceive obesity to be a present or potential problem. OUTCOMES: The task
      force reviewed the probability of obese children become obese adults as a risk
      factor for adult heart disease and overall related illness and death in adult
      life as well as obesity as a risk factor for physical and psychologic illness in
      childhood. EVIDENCE: A MEDLINE search for relevant articles published between
      January 1981 and February 1991 was undertaken. VALUES: The task force's evidence
      based rules for recommendations were used. BENEFITS, HARMS AND COSTS: If weight
      reduction in childhood were shown to prevent physical or psychologic illness in
      childhood, or illness and death in adult life, screening and treatment should be
      recommended. Screening for obesity may cause anxiety on the part of the child and
      family; malnutrition in children as a result of parents becoming overly anxious
      about the health risks of obesity has been reported. Most weight reduction
      programs have limited long-term effectiveness and can be costly. RECOMMENDATIONS:
      There is insufficient evidence of short-term or long-term benefits from screening
      for or treatment of childhood obesity to recommend such screening or recommend
      against it. There is fair evidence to recommend against very-low-kilojoule diets
      for preadolescents. There is insufficient evidence to recommend for or against
      exercise programs or intensive family-based programs for most obese children.
      VALIDATION: These recommendations are similar to those of the American Academy of
      Pediatrics and the US Preventive Services Task Force. SPONSOR: These guidelines
      were developed and endorsed by the Canadian task force, which is funded by Health
      Canada.

PMID- 8131122
TI  - Physicians in health care management: 3. Case Mix Groups and Resource Intensity
      Weights: an overview for physicians.
AB  - In the first of two articles on the subject, the authors explain what Case Mix
      Groups (CMGs) and Resource Intensity Weights (RIWs) are and how they are used.
      The former categorize hospital patients into groups. The latter are ratios
      showing the relative use of hospital resources for a typical case (successful
      course of treatment in an acute care hospital and discharge when the patient no
      longer requires the hospital's services) and atypical cases (death, transfer,
      sign-out and substantially longer than average stay) in each CMG. As such, CMGs
      and RIWs define the relation between the medical and financial dimensions of
      hospital cases for use in planning and management. Ontario and Alberta are the
      first provinces to use them to adjust hospital funding. CMGs are limited by the
      number of diagnoses contained in each category, and RIWs are limited by the use
      of New York cost data due to the lack of Canadian data.

PMID- 8131123
TI  - Canadian study of health and aging: study methods and prevalence of dementia.
AB  - OBJECTIVE: To estimate the prevalence of dementia and its subtypes by sex and age
      group for five regions of Canada. DESIGN: Prevalence survey. SETTING: Community
      and institutional settings in Canada, excluding those in the two territories,
      Indian reserves and military units. PARTICIPANTS: Representative sample of people
      aged 65 and over interviewed between February 1991 and May 1992. Those in the
      community (9008 subjects) were chosen randomly from medicare lists in nine
      provinces or from the Enumeration Composite Record in Ontario. People in
      institutions (1255) were randomly selected from residents in stratified random
      samples of institutions in each region. INTERVENTIONS: Screening with the
      Modified Mini-Mental State (3MS) Examination to identify cognitive impairment.
      Clinical examination of all those in institutions, those in the community with a
      3MS score of less than 78 and a sample of those in the community with a 3MS score
      of 78 or more to diagnose dementia. Dementia and Alzheimer's disease were defined
      according to established criteria. MAIN OUTCOME MEASURES: Prevalence of dementia
      of all types, by region, sex and age group, the estimated number of cases in the
      population by type of dementia and the age-standardized rate per 1000 population.
      RESULTS: The prevalence estimates suggested that 252,600 (8.0%) of all Canadians
      aged 65 and over met the criteria for dementia (95% confidence interval [CI]
      236,800 to 268,400). These were divided roughly equally between the community and
      institutional samples; the female:male ratio was 2:1. The age-standardized rate
      ranged from 2.4%, among those aged 65 to 74 years, to 34.5%, among those aged 85
      and over. The corresponding figures for Alzheimer's disease were 5.1% overall
      (161,000 cases; 95% CI 148,100 to 173,900), ranging from 1.0% to 26.0%; for
      vascular dementia it was 1.5% overall, ranging from 0.6% to 4.8%. If the
      prevalence estimates remain constant, the number of Canadians with dementia will
      rise to 592,000 by 2021. CONCLUSIONS: These Canadian estimates of the prevalence
      of dementia fall toward the upper end of the ranges in other studies, whereas the
      estimates for Alzheimer's disease fall in the middle of the ranges. This may
      suggest an unusual balance between Alzheimer's and other forms of dementia in the
      Canadian population.

PMID- 8131125
TI  - Acanthamoeba keratitis: an emerging clinical problem.

PMID- 8131124
TI  - Relation between physician characteristics and prescribing for elderly people in
      New Brunswick.
AB  - OBJECTIVE: To determine whether there is a relation between physician
      characteristics and prescribing for elderly patients. DESIGN: Descriptive study
      linking two provincial databases. SETTING: New Brunswick. PARTICIPANTS: All
      general practitioners (GPs) in New Brunswick who ordered at least 200
      prescriptions for elderly beneficiaries of the New Brunswick Prescription Drug
      Program between Apr. 1, 1990, and Mar. 31, 1991; eligible GPs accounted for 376
      (40%) of all physicians with a general licence in New Brunswick. MAIN OUTCOME
      MEASURES: GPs' personal and professional characteristics (age, sex, family
      practice accreditation, country of training and number of years in practice),
      practice characteristics (number of practice days, number of patients seen and
      medical services provided per day, average amount of billing per patient, total
      number of patients seen and their average age, and total amount of billings) and
      number of prescriptions by category of drug. RESULTS: High prescribers and low
      prescribers did not differ significantly in age, number of years in practice,
      mean practice size or patient age. Compared with the low prescribers the high
      prescribers were more likely to be male, have been trained in Canada and be
      qualified by the Canadian College of Family Physicians. Also, they had more
      practice days, saw more patients per day, performed more services per day, billed
      more per patient and billed on average 30% more during the study period. Overall,
      the high prescribers ordered on average 45% more prescriptions than the low
      prescribers. CONCLUSION: There is a significant relation between certain
      physician characteristics and prescribing behaviour. Further study is required to
      examine the relation between these variables and patient outcomes.

PMID- 8131126
TI  - Antibiotics and resistance: hand in hand?

PMID- 8131127
TI  - Academic medicine and the pharmaceutical industry: a cautionary tale.

PMID- 8131128
TI  - We need dialogue and discussion, not a new Berlin Wall.

PMID- 8131129
TI  - Ottawa throws weight behind regulations concerning very-low-energy diets.

PMID- 8131130
TI  - Psychiatrist's release of confidential information causes controversy in Halifax.

PMID- 8131131
TI  - The 1994 CIMS match: it's deja vu all over again.

PMID- 8131132
TI  - Labour-management software provides "decision-support system" for obstetric
      units.

PMID- 8131133
TI  - Infertility treatment targeted as Ontario delists services.

PMID- 8131134
TI  - Psychiatry without borders: European union accentuates different approaches to
      psychiatry.

PMID- 8131135
TI  - Canadian physicians may hear footsteps of change as US tiptoes toward health care
      reform.

PMID- 8131136
TI  - Are your patients fit to drive?

PMID- 8131137
TI  - Nutrition education--beyond the facts.

PMID- 8131138
TI  - Food and nutrition in Canadian "prime time" television commercials.
AB  - Television is, arguably, the most influential mass medium and "prime time"
      viewing attracts the largest audiences. To assess the type, number and
      nutritional content of foods advertised on TV, commercial breaks during "prime
      time" (7:00 to 11:00 p.m.) on five Canadian channels (CBC-English, CBC-French,
      CTV, CFPL, Much Music) were recorded and analyzed. A similar analysis of Saturday
      morning children's TV commercials was also performed. Commercials for foods and
      food products constituted between 24-35% of all commercials, the largest
      advertising output for any group of products. The combination of food presented
      in commercials reflected average current consumption patterns. Of special concern
      was the emphasis on low nutrition beverages, especially beer, as well as snacks
      and candy on Much Music. While further government intervention to restrict
      advertising practices may be an impractical option, there is scope for increasing
      the alternative promotion of healthy dietary choices.

PMID- 8131139
TI  - [The effects of a nutritional information program on the contents of grocery
      carts].
AB  - In 1988, a chain of supermarkets in Quebec organized and sponsored a campaign to
      promote healthy eating habits and regular physical activity. Over a six-week
      period, comprehensive articles were published in a free home-delivered flyer.
      This study aimed to determine the effectiveness of the program in changing the
      buying habits of customers, as reflected by the content of their grocery carts.
      Data were collected at four points in time in one supermarket. Four independent
      samples of customers (N = 465) answered a brief questionnaire and the grocery
      receipt was used to analyze the food items in their shopping carts. The major
      dependent variables were the portions of various food groups, and fiber and lipid
      densities per dollar. Results show that, over time, customers lowered the lipid
      content and increased the fiber content of their purchases. This suggests that
      the food industry can play an effective role in improving the well-being of their
      clients.

PMID- 8131140
TI  - Changes in knowledge and food behaviour following a screening program held in a
      supermarket.
AB  - We examined the relationship between knowledge, health beliefs and dietary
      behaviours of participants in a supermarket cardiovascular screening program, the
      conceptual framework for which was the Health Belief Model. 3,432 individuals
      aged 18-74 participated in the screening program conducted in 54 supermarkets in
      Montreal and Quebec. This program identified participants' risk for
      cardiovascular disease by measuring total serum cholesterol, blood pressure,
      height, weight, level of physical activity, and tobacco use. A ten-minute
      debriefing counselling session interpreted risk factors and recommended follow
      up. 70% (n = 2,420) also completed a nutrition questionnaire on knowledge, health
      beliefs, and frequency of consumption of high fat foods. Respondents increased
      their knowledge and reduced the frequency of consumption of high-fat foods
      following the screening program (p < or = 0.05), particularly individuals with
      higher blood cholesterol levels, high blood pressure, and women.

PMID- 8131141
TI  - The Manitoba Nutrition Survey: fat consumption data.
AB  - A nutrition survey was conducted as part of a larger cardiovascular risk study
      undertaken by the Manitoba Heart Health Project. A representative group of
      Manitobans participated in the study, 68% of whom reported their food intake
      using a food frequency questionnaire. After verifying and merging data from the
      nutrition and risk factor questionnaires used in the survey, 2,115 were used in
      data analysis. Results are reported by gender for three age groups. The
      proportion of food energy derived from total fat varied between 35.3% for senior
      females and 40.2% for young males. Food of seniors contained a lower proportion
      of energy from fat than that of either of the two younger age groups. In all
      three age groups, men consumed diets with a higher proportion of fat than did
      women. People in regional centres and rural areas obtained higher proportions of
      energy from fat than did people in Winnipeg. Fat intake from butter, margarine or
      spreads eaten with bread and potatoes was high compared to the intake from other
      foods.

PMID- 8131142
TI  - Vitamin D deficiency in a Manitoba community.
AB  - OBJECTIVE: Using a cross-sectional survey, to investigate the vitamin D status of
      a random sample of 80 mother-child pairs (child age 3-24 months) in a Manitoba
      community with a high incidence of rickets. METHOD: A questionnaire on feeding
      habits, gestational history, maternal diet and vitamin supplements was
      administered to mothers in their homes with the assistance of a local
      interpreter. Venous blood was collected from both mother and child for serum 25
      hydroxyvitamin D levels. RESULTS: Of 91% babies initially breastfed, 36% received
      no formula or milk after weaning and 40% received no vitamin supplements. 24% of
      mothers took no vitamin supplements during pregnancy and lactation. Knowledge
      about rickets was poor. In 43% of children and 76% of mothers, serum 25
      hydroxyvitamin D levels were below normal range. CONCLUSIONS: Vitamin D levels
      are low in this population due to lack of fortified dairy products and vitamin D
      supplements. A public health program should include counseling on rickets and
      vitamin D supplementation for all infants and pregnant or lactating women.

PMID- 8131143
TI  - Evaluation of the Heart Smart Restaurant Program in Saskatoon and Regina,
      Saskatchewan.
AB  - The consumer-driven Heart Smart Restaurant Program was developed by the Heart and
      Stroke Foundation of Saskatchewan and the Saskatoon Community Health Unit, with
      the aim of improving the nutritional quality of food consumed in table-service
      restaurants. To participate, restaurateurs must agree to provide smoke-free
      seating and specific more healthful food choices upon request of the customer.
      The program was evaluated through telephone interviews with 999 individuals in
      randomly selected households in Saskatoon and Regina. While public awareness of
      the program was satisfactory, over half of those who knew of the program
      misunderstood its function, believing that more healthful choices are indicated
      on the menu. When choosing a restaurant, individuals are not greatly influenced
      by whether it is Heart Smart, but in Saskatoon, they are more likely to request a
      more healthful alternative in a Heart Smart restaurant than in others.
      Implications of these and other findings for future program development and
      research are discussed.

PMID- 8131144
TI  - Re: Alcohol use and abuse in Canada and mortality from suicide.

PMID- 8131145
TI  - [Nutritional recommendations and risk of death from all causes].
AB  - This study evaluated the relationship between meeting the Nutrition
      Recommendations and mortality from all causes in a cohort of 1,623 men from the
      Quebec City area followed from 1985 to 1991. The usual dietary intake was
      assessed by a self-administered semi-quantitative food frequency questionnaire.
      Most participants did not meet the Nutrition Recommendations. During the follow
      up 69 men died. The mortality was significantly lower among those who did not
      meet the recommendations for total fat (RR = 0.45, CI: 0.25-0.81) or for
      carbohydrates (RR = 0.49, CI: 0.26-0.92). This unexpected result could be
      attributable to an excessive alcohol intake or to dietary changes in the
      direction of the Nutrition Recommendations, made prior to the dietary assessment
      often because of illness. It would be interesting to continue the follow-up of
      this cohort to evaluate the long-term effect of a diet meeting the Nutrition
      Recommendations on mortality from all causes.

PMID- 8131146
TI  - Directing our future: objective-oriented program planning by public health
      nutritionists.

PMID- 8131147
TI  - A survey of breakfast-skipping and inadequate breakfast-eating among young
      schoolchildren in Nova Scotia.
AB  - The prevalence of breakfast-skipping and inadequate breakfast-eating among
      schoolchildren in Nova Scotia was determined by surveying 2,500 children in
      Grades 1 to 3 in 25 randomly selected schools. Breakfast-skipping was measured on
      two occasions using a validated survey instrument administered by videotaped
      child entertainers. 4.8% of children came to school without eating or drinking
      anything on the morning of testing. Breakfast omission was significantly related
      to grade with 6.1% of Grade 1 children skipping breakfast compared with 3.2% in
      Grade 3. Boys were significantly more likely to skip breakfast than girls but the
      absolute differences were small. 86% of children consumed a breakfast including
      two food groups; 56% three food groups. Adequacy of consumption was poorer in
      lower grades but did not vary by other sociodemographic variables. Breakfast
      omission in Nova Scotia children attending Grades 1, 2 or 3 does not warrant a
      provincial public health response.

PMID- 8131148
TI  - Community risk perception: a case study in a rural community hosting a waste site
      used by a large municipality.
AB  - Using a model of risk perception which divides the community into attitudinal and
      behavioural subgroups based on awareness, concern and action in relation to a
      waste management facility, we conducted a survey in a community with an operating
      landfill and a ten-year history of controversy over the unsuccessful siting of a
      hazardous waste facility (HWF). The purpose of the survey was to study community
      attitudes to waste management in general, attitudes specific to landfills and
      HWFs, and to identify factors which shape community attitudes in both cases.
      Levels of concern and activism were lower for the landfill; activism and concern
      were more likely among younger subjects and those with children. In the case of
      the HWF, greater concern and activism were more likely among married people and
      those without a university education. Gender differences in relation to
      environmental "concern" were not found for either the landfill or the HWF siting
      attempts.

PMID- 8131149
TI  - The hopes and hazards of health goals development.
AB  - As part of the Edmonton Board of Health's centennial celebrations, health goals
      and objectives were developed for the city. The intensely collaborative process
      used to develop the goals and objectives is reviewed and critical activities such
      as communication, media and community involvement, committee membership, and
      implementation are discussed. It is hoped that the information will be useful for
      others who are developing health goals and objectives at the municipal level.

PMID- 8131150
TI  - Sociodemographic correlates for risk-taking behaviour among HIV seronegative
      homosexual men.
AB  - The aim of this paper is to determine the sociodemographic characteristics of
      seronegative men engaging in behaviours at high risk for HIV transmission within
      a cohort of homosexual men. Eligible subjects in the cohort (n = 139) were those
      who were HIV negative and who completed an index visit between October 1989 and
      September 1990 and reported having sexual contact with casual partners during the
      previous 12-month period. Risk-takers (n = 31) were those who reported having
      unprotected anal receptive or insertive intercourse with casual partners; while
      the remaining subjects (controls) (n = 108) were those who reported either not
      engaging in anal intercourse with casual partners or using condoms when they did.
      Risk-takers were significantly younger and were more likely than controls to have
      incomes below $10,000, to smoke cigarettes and to use nitrite inhalants. Our
      findings suggest the importance of targeting AIDS prevention activities to
      specific subgroups within the gay community who are more at risk of HIV
      infection.

PMID- 8131151
TI  - Serotonin receptor subtypes and affective disorders.
AB  - The role of drugs that act at 5-hydroxytryptamine (5-HT or serotonin) receptor
      subtypes in the etiology and treatment of affective disorders is discussed. The
      mechanisms of action of drugs affecting 5-HT are described, with emphasis on
      those with anxiolytic and antidepressant activity. Evidence supporting a role for
      serotonin in the etiology and treatment of affective disorders in cited. Recent
      therapeutic advances have resulted in a new generation of serotonergic drugs.

PMID- 8131152
TI  - Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in
      major depressive disorder: neuroendocrine and platelet markers.
AB  - Neuroendocrine and platelet markers of serotonin (5-hydroxytryptamine, 5-HT)
      receptor functioning are useful tools for studying the downregulation of 5-HT
      receptors, a leading hypothesis for the mechanism of action of antidepressant
      drugs. The 5-HT releaser fenfluramine raises body temperature as well as plasma
      concentrations of ACTH, cortisol, and prolactin. Pretreatment with the 5-HT1
      antagonist pindolol did not block the hyperthermic response to fenfluramine,
      mediating its actions via non-5-HT1 receptor subtypes (presumably 5-HT2/1C). We
      observed blunted hyperthermic responses to fenfluramine in unmedicated patients
      with major depressive disorder. We also observed that the neuroendocrine
      responses to fenfluramine were decreased by chronic treatment with the tricyclic
      antidepressant nortriptyline but not by chronic treatment with tricyclic
      antidepressant nortriptyline but not by chronic treatment with adinazolam, a
      triazolobenzodiazepine with purported antidepressant activity. IC50 values for
      ketanserin inhibition of 5-HT-induced platelet shape change response, a marker of
      5-HT2/1c receptors, were elevated after nortriptyline treatment in depressed
      patients, and this increase could be accounted for by those subjects who
      responded well to antidepressant treatment. Adinazolam treatment did not alter
      the platelet shape change response. Our data suggest that downregulation of 5
      HT2/1c receptors may be linked to the clinical response of depressed patients
      treated with nortriptyline.

PMID- 8131153
TI  - Serotonin selective antidepressant drugs: past, present, future.
AB  - Classic antidepressant drugs, amine uptake inhibitors of the imipramine type and
      the monoamine oxidase inhibitors, alter the functioning of serotonin (5
      hydroxytryptamine, 5-HT) neurons in the brain. This discovery, made more than two
      decades ago, has had a profound impact on the study of depressive illness as well
      as on the development of new models of antidepressant treatment. Apart from their
      obvious clinical value, antidepressant drugs have come to be used as research
      tools to study the pathophysiology of depressive illness. A main goal in the
      development of antidepressant drugs has been to design drugs with more selective
      effects on the nerve cells that are thought to be important in depressive
      illness, thereby avoiding unnecessary side effects and possibly enhancing
      therapeutic effects. Drugs that selectively affect 5-HT neurons have proved to be
      uptake inhibitors--including fluoxetine, fluvoxamine, paroxetine, sertraline, and
      citalopram--and are now available. All of them appear to have an antidepressant
      effect equivalent to standard reference compounds, with a different spectrum of
      side effects. One of the most interesting aspects of the serotonergic drugs is
      their broad spectrum of action, in particular, their effects in patients with
      obsessive-compulsive disorder, panic disorder, and possibly some disorders of
      impulse control. There is still relatively little knowledge of which aspects of 5
      HT function are important for the antidepressant, antiobsessive, and antipanic
      effects. The availability of drugs that selectively affect the different 5-HT
      receptors, such as the partial 5-HT1A agonist gepirone, will presumably be
      helpful for modern studies of the "anatomy of melancholy."

PMID- 8131154
TI  - Novel serotonergic mechanisms and clinical experience with nefazodone.
AB  - Chronic administration of antidepressant drugs enhances synaptic serotonergic
      transmission. Nefazodone, a member of a new class of antidepressants, has a
      pharmacologic profile that is distinct from the first-generation agents (e.g.,
      tricyclics and monoamine oxidase inhibitors) as well as the more selectively
      acting second-generation agents (e.g., serotonin or norepinephrine uptake
      inhibitors, and serotonin type 1A partial agonists). Nefazodone acts both as a 5
      HT2 receptor antagonist and as a serotonin (5-HT) reuptake inhibitor.
      Nefazodone's potent 5-HT2 antagonism in combination with 5-HT reuptake inhibition
      appears to enhance 5-HT1A-mediated neurotransmission. Nefazodone has very
      selective serotonergic effects, with negligible affinity for cholinergic and
      histamine receptors and low affinity for alpha 1-adrenergic receptors. It is also
      free of cardiotoxicity and is well tolerated even at high doses. The two primary
      effects on serotonergic neurotransmission, 5-HT2 antagonism and 5-HT reuptake
      inhibition, are thought to contribute importantly to nefazodone's therapeutic
      efficacy and clinical utility. It is postulated that 5-HT2 antagonism dampens the
      activating side effects experienced by some patients when treated with existing 5
      HT reuptake inhibitors. Nefazodone's effectiveness as an antidepressant drug has
      been shown in a series of well-controlled, placebo-comparison studies of somewhat
      differing designs involving patients with major depression. In placebo-controlled
      studies comparing nefazodone and the tricyclic antidepressant imipramine, the
      drugs produced comparable and significant therapeutic benefit. Nefazodone is
      associated with fewer adverse events than imipramine. Nefazodone lacks the
      troublesome anticholinergic side effects of tricyclic antidepressants, as well as
      serotonergic/noradrenergic-mediated effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131155
TI  - Serotonin receptor subtypes in depression: evidence from studies in
      neuroendocrine regulation.
AB  - Serotonin (5-HT) neuroendocrine tests are a valid and acceptable means of
      measuring 5-HT neurotransmission in humans. Recently, the availability of
      selective 5-HT receptor ligands has allowed the assessment of specific 5-HT
      receptor subtype function using neuroendocrine methods. Studies with selective
      antagonists have shown that the endocrine responses to the 5-HT precursor L
      tryptophan (LTP) are mediated via postsynaptic 5-HT1A receptors, whereas
      endocrine responses produced by the 5-HT-releasing agent d-fenfluramine involve
      postsynaptic 5-HT2/1C receptors. Endocrine responses to both LTP and fenfluramine
      are consistently decreased in depressive illness. In contrast, endocrine
      responses to direct 5-HT1A and 5-HT2/1C receptor agonists are not consistently
      attenuated in depressed patients. The current data suggest that depressive
      illness is associated with an impairment of 5-HT neurotransmission that involves
      decreased 5-HT release rather than altered sensitivity of postsynaptic 5-HT
      receptors.

PMID- 8131156
TI  - Synthesis of 2,3-di-O-glycosyl derivatives of methyl alpha- and beta-D
      glucopyranoside.
AB  - The syntheses are described of 2,3-di-O-glycosyl derivatives of methyl alpha- and
      beta-D-glucopyranoside having alpha-D-manno-, beta-D-galacto-, alpha-L-rhamno-,
      alpha-L-fuco-, and beta-L-fuco-pyranosyl substituents at O-2 and O-3. The
      syntheses involved glycosylation of methyl 4,6-O-benzylidene-alpha- (24) and 
      beta-D-glucopyranoside (21), and substituted derivatives of 21 bearing 2-O
      (2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl)-, -(2,3,4,6-tetra-O- acetyl-beta
      D-galactopyranosyl)-, -(2,3,4,-tri-O-benzoyl-alpha-L- rhamnopyranosyl)-, and 
      (2,3,4-tri-O-benzoyl-beta-L-fucopyranosyl) groups.

PMID- 8131157
TI  - Wittig reaction of unprotected D-aldopentoses with stabilized ylides: metal-ion
      effects.
AB  - Each of the four D-aldopentoses (1-4) reacts in the unprotected form with
      Ph3PCHCO2Me (5) in THF to give stereoselectively the corresponding trans
      alpha,beta-unsaturated C7 Wittig adducts, isolated as the corresponding 4,5,6,7
      tetraacetates (7-10) or 4,5:6,7-di-O-isopropylidene derivatives (11-14).
      Concurrently formed are also bicyclic, 1,4-lactone derivatives, isolated as their
      5,7-diacetates (15-18) or 5,7-O-isopropylidene derivatives (19), arising through
      intramolecular Michael addition from the initial acyclic adducts. Formation of
      the cyclized products is suppressed by incorporation of Cu(OAc)2 in the reaction
      mixture, permitting preparative isolation of the hept-3-enonate derivatives 7-10,
      useful as dienophiles in Diels-Alder carbocyclizations with chirality transfer.
      Optimized yields were 25% (D-ribo), 50% (D-arabino), 49% (D-xylo), and 61% (D
      lyxo). Under Cu(OAc)2-catalyzed conditions, the formation of small proportions of
      3,7-anhydroheptonic acid esters (21 and 23) was observed in the D-arabino and D
      xylo series, but not with the other two pentoses.

PMID- 8131158
TI  - Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars: reactivities of
      acyclic seven-carbon trans dienophiles derived from aldopentoses.
AB  - Acyclic trans-2,3-unsaturated aldoheptonate derivatives (1-9) obtained from D
      aldopentoses by Wittig chain-extension served as dienophiles for a detailed
      comparative study of their asymmetric Diels-Alder cycloaddition with
      cyclopentadiene. Cycloaddition under uncatalyzed thermal conditions gave mixtures
      of the four possible stereoisomeric norbornene adducts. The endo:exo ratios and
      the diastereofacial selectivities in the formation of the adducts were determined
      by NMR spectroscopy and by chemical transformations. The quantitative
      distribution of adducts as a function of stereochemistry of the dienophile is
      discussed.

PMID- 8131159
TI  - Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars: reactivities of
      cis-dienophiles with cyclopentadiene.
AB  - Cycloaddition of cyclopentadiene with a D-arabinose-derived cis-dienophile,
      methyl (Z)-4,5,6,7-tetra-O-acetyl-2,3-dideoxy-D-arabino-hept-2-enonate (2), under
      thermal conditions gave essentially a single norbornene adduct, isolated
      crystalline in 81% yield and identified by NMR spectroscopy and X-ray
      crystallography as methyl (5R,6S)-6-endo-(1,2,3,4-tetra-O-acetyl-D-arabino
      tetritol-1-yl)bic yclo [2.2.1]-hept-2-ene-5-endo-carboxylate (3). The diene adds
      exclusively from the si-face of the dienophile and give only the endo product.
      The same sequence starting from L-arabinose gave the enantiomer (7) of 3. In
      contrast, a related cis-dienophile (9) having a butenolide ring reacts with
      cyclopentadiene from the opposite (re) face giving mainly the endo adduct (5S,6R)
      6-endo-(2,3,4-tri-O-acetyl)-D-arabino-tetritol-1-yl)bicycl o [2.2.1]hept-2-ene-5
      endo-carboxylic acid 1,4-lactone (10), isolated crystalline in 70% yield, whose
      structure was again established by NMR spectroscopy, and firmly consolidated by X
      ray crystallography. The minor (11%) product was the exo(5S,6R) isomer 11. A cis
      enonate 14, analogous to 2 but deoxygenated at the allylic position, showed
      negligible diastereofacial selectivity and reacted with cyclopentadiene to give a
      mixture of all four possible adducts. A 6-membered ring dienophile 16 was also
      subjected to the same cycloaddition for comparison with the butenolide 9; it gave
      principally the two endo products 17 and 19 in 31 and 38% yields, respectively,
      accompanied by 12% of a mixture of the two exo products (18 and 20). The
      quantitative distribution of cycloaddition products as a function of dienophile
      stereochemistry is discussed. The high degree of asymmetric induction observed,
      especially with the readily accessible dienophiles 2 and 7, provides a valuable
      route of access to enantiomerically pure tetra-C-substituted cycloalkanes.

PMID- 8131160
TI  - Chemical structure and conformational features of cell-wall polysaccharides
      isolated from Aphanoascus mephitalus and related species.
AB  - The structures of cell-wall mannans isolated from Aphanoascus mephitalus, A.
      fulvescens, A. verrucosus, and A. reticulisporus have been investigated by
      chemical analyses and 1D and 2D 1H and 13C NMR techniques. It was found that all
      of them consists of a relatively simple comb-like structure of the disaccharide
      repeating block [-->6)-[alpha-Manp-(1-->2)]-alpha-Manp-(1-->]. The conformations
      around the alpha-(1-->2) and alpha-(1-->6) linkages in these kinds of polymers
      were also studied by using molecular mechanics and dynamics calculations,
      together with NOE data. The results are similar to those found within the
      oligosaccharide chains of glycoproteins, with a well-defined conformation for the
      alpha-(1-->2) linkage and a certain restriction around the alpha-(1-->6) bonding
      imposed by the 2-substitution.

PMID- 8131161
TI  - Synthesis of the 3-deoxy-3-C-(phosphonomethyl) analogue of 1D-myo-inositol 3
      (dihydrogenphosphate).

PMID- 8131162
TI  - Primary structure of the polysaccharide chain of virulent Pseudomonas
      solanacearum biotype II lipopolysaccharide.

PMID- 8131163
TI  - Self-expandable macroporous nitinol stents for transfemoral exclusion of aortic
      aneurysms in dogs: preliminary results.
AB  - This experimental study evaluated the feasibility of excluding artificially
      created aortic aneurysms in dogs with transfemorally inserted nitinol stents,
      serving as intraluminal bypass. Infrarenal aortic aneurysms were created in
      eleven dogs (28-35 kg) by end-to-end anastomosis of sacciform conduits. Single
      and double wire-knitted, macroporous, superelastic, self-expanding nitinol stents
      without any additional wrapping or in-between fabrics served as endovascular
      grafts. The pore size of the double-knitted stents was less than 0.7 mm2.
      Angiography following stent placement showed immediate exclusion of the aneurysms
      for the double-knitted stents. For the single-knitted stents (2 cases), partial
      exclusion was achieved only after considerable delay. CT studies in the dogs with
      the double-knitted stents revealed patency of the grafts after 3 to 5 weeks with
      the aneurysms totally thrombosed. So far gross pathology of 1 dog at 24 h and 1
      at 12 months revealed patency of the stents. At 12 months histopathology showed a
      neointima covering the inner stent surface with the aneurysm filled by an
      organized thrombus. It is concluded, that an "open" stent with a tight meshwork
      appears to be a suitable device to instantly exclude artificial aneurysms of the
      canine aorta.

PMID- 8131164
TI  - Effects of iomeprol, a new nonionic contrast medium, vis a vis iopamidol and
      nitroglycerin, on coronary diameter and blood flow in chronically instrumented
      dogs.
AB  - The effects of an intracoronary administration of iomeprol, a new nonionic tri
      iodinated water-soluble contrast medium, on coronary circulation were compared to
      those of iopamidol and those of nitroglycerin in 6 chronically instrumented
      conscious dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic
      flow probe were placed on the left circumflex coronary artery (LCCA) to measure
      the epicardial coronary diameter (CD) and coronary blood flow (CBF). Polyethylene
      tubing for drug administration was inserted into the LCCA proximal to the
      sonomicrometers. Iomeprol at the dose of 1 ml and 3 ml/min for 1 min
      significantly increased CD by 0.6 +/- 0.1% and 1.4 +/- 0.3%, respectively and CBF
      by 44.5 +/- 9% and 70 +/- 10%, respectively. Iopamidol at the same rates also
      significantly increased CD by 0.8 +/- 0.1% and 1.5 +/- 0.3% and CBF by 50 +/- 11%
      and 82 +/- 14%, respectively. There was no statistically significant difference
      between iomeprol- and iopamidol-induced increases in CD and CBF. However, the
      duration of the increase in CD was significantly shorter (p < 0.05) after
      iomeprol than after iopamidol. Nitroglycerin (10 micrograms/kg) significantly
      increased CD by 4.5 +/- 1% and CBF by 105 +/- 10%. The increases in CD and CBF in
      response to iopamidol and iomeprol were significantly smaller (p < 0.01) than to
      nitroglycerin. We conclude that vasodilating effects of iomeprol and iopamidol on
      the large epicardial coronary artery and coronary blood flow are comparable in
      conscious dogs and significantly lower than after nitroglycerin in the doses used
      by us.

PMID- 8131165
TI  - Effects of hepatic artery embolization with Lipiodol and gelatin sponge particles
      on normal swine liver.
AB  - In order to evaluate the effects of hepatic artery embolization (HAE) with
      Lipiodol (Lp) and gelatin sponge particles (GSP) on swine liver tissue, we
      embolized the hepatic arteries of 3 pigs with GSP, 9 with Lp, and 9 with Lp +
      GSP. None of the pigs embolized with GSP died spontaneously during the 4-week
      experimental period. One pig embolized with 1 ml/kg Lp and three pigs with 2
      ml/kg Lp died within 2 h. Two pigs embolized with 0.5 ml/kg Lp + GSP died the
      following day. The portal vein pressure (PVP) and wedge hepatic vein pressure
      (WHVP) values before HAE, immediately after, 1 h after, and 4 weeks after HAE
      showed no remarkable change in the GSP group. Remarkable and temporary elevation
      was observed in the more than 0.2 ml/kg Lp group. Remarkable and continuous
      elevation was observed in the 0.2 ml/kg Lp + GSP and 0.5 ml/kg Lp + GSP groups.
      Gross and histological studies demonstrated no liver damage in the GSP and Lp
      group. Liver infarction, circular coagulation necrosis with pseudocapsule, and
      liver atrophy were found in the Lp + GSP group 4 weeks after HAE. The incidence
      of infarction, circular coagulation necrosis, and liver atrophy in the livers
      embolized with 0.2 ml/kg Lp + GSP and 0.5 ml/kg Lp + GSP were 67%, 100%, and 75%,
      respectively. In conclusion, when the hepatic artery is embolized with Lp + GSP,
      the volume of Lp should be limited to less than 0.1 ml/kg.

PMID- 8131166
TI  - Long-term control of hypertension and the predictive value of peripheral plasma
      renin activity after ablation of end stage kidneys with a new embolic agent.
AB  - Embolization of end-stage kidneys using our own embolizing agent Vilanol
      (partially hydrolyzed polyvinyl acetate) was performed in 10 patients with
      hypertension refractory to conservative therapy. Native kidneys were embolized in
      7 patients with chronic renal failure, nonfunctioning renal transplants in 2
      patients, and a shrunken kidney in 1 patient. Five of the 10 patients had high
      (9.96-18.2 ng/ml/h) peripheral renin (PR) levels. The embolization was
      technically successful in 4 of these 5 patients and was immediately followed by a
      marked decrease in PR, and simultaneous improvement in blood pressure (BP). The
      other 5 patients had very low PR levels (0.07-0.65 ng/ml/h), and a reduction in
      BP was observed in 4 after embolization. One patient died following embolization
      from cardiac arrest due to hyperkalemia. Six patients (3 in each group) have been
      on follow-up for 2-5 years with sustained decrease in BP. We conclude that the
      new agent is effective for renal ablation and control of refractory hypertension.

PMID- 8131167
TI  - Embolization of renal vascular lesions: clinical experience with microcoils and
      tracker catheters.
AB  - After biopsy (n = 6) and nephrostomy (n = 1) of three native and four
      transplanted kidneys, gross hematuria, hypertension, and deterioration of
      function necessitated performance of transarterial embolization. Angiography
      revealed five arteriovenous fistulas (AVFs), one pseudoaneurysm, and one
      arteriocaliceal fistula. Superselective catheterization was accomplished using 5
      Fr standard diagnostic catheters and 3 Fr coaxial Tracker catheters. Four of five
      AVFs were embolized successfully by inserting unfibered (2 patients) and fibered
      (2 patients) platinum coils (diameters 2 mm and 4 mm, respectively). For one AVF,
      additional injection of butylcyanoacrylate was necessary. The pseudoaneurysm was
      embolized successfully by such injection, and the arteriocaliceal fistula was
      occluded using one unfibered 2-mm coil. Embolization stopped the bleeding in all
      patients. One week after treatment, renal function was improved in 5 patients and
      remained unaffected in 2. Superselective embolization using Tracker catheters and
      fibered microcoils is an effective, safe treatment of renal vascular lesions.

PMID- 8131168
TI  - Intrahepatic arterioportal fistulae: role of transcatheter embolization.
AB  - Management of 26 arterioportal fistulae (APFs) is reported. Among 13 hepatoma
      induced fistulae (group A), conservative treatment was ineffective in 8 patients,
      and arterial embolization alleviated portal hypertension in the other 5. Of 10
      iatrogenic APFs (group B), the 3 largest were successfully embolized, the
      remaining lesions resolved spontaneously. Three spontaneous nonmalignant APFs
      (group C) were embolized. Excellent results were obtained in 2 patients, and the
      other died of severe postembolization hepatic failure. Because long-standing APFs
      may cause severe portal hypertension with consequent variceal bleeding they
      should be treated. Arterial embolization is indicated in most patients.

PMID- 8131169
TI  - Percutaneous angioscopy: improved technique.
AB  - Ten angioscopies with a pressure infusion set resulted in similar visualization
      times and irrigation volumes as 42 angioscopies with a specially constructed
      roller pump. Diagnostic image quality, however, was obtained almost exclusively
      with the roller pump. Three examinations were nondiagnostic. Total viewing time
      per patient was approximately 1 min with the roller pump and 2 min with the
      pressure infusion system. In the 30 patients examined, angioscopy changed the
      initially chosen form of therapy in 5 patients.

PMID- 8131170
TI  - Persistent sciatic artery: bilateral percutaneous transluminal angioplasty in
      ischemic disease.
AB  - Persistent sciatic artery (PSA) is a rare vascular anomaly that results from
      failure of an embryonal artery to the lower extremities to regress during fetal
      development. Aneurysm formation, thromboembolism, and arterial occlusions may
      complicate this abnormality. We report a patient with complete bilateral PSA and
      intermittent claudication who was treated by bilateral percutaneous angioplasty.

PMID- 8131171
TI  - Delayed hemorrhage following transcatheter arterial embolization for blunt
      hepatic injury.
AB  - This is the first report of delayed hemorrhage (21 days after the injury)
      following transcatheter arterial embolization (TAE) for severe hepatic injury.
      The first TAE was performed about 2 h after admission on a 21-year-old man with
      severe blunt hepatic injury. Three bilomas were detected by cholescintigraphy 19
      days later. The patient's status had been eventless until the occurrence of a
      delayed hemorrhage with hypotension. Angiography was repeated and three
      pseudoaneurysms were detected in the same areas as the bilomas. With repeated
      TAE, pseudoaneurysms disappeared and hemorrhage could be controlled. Intrahepatic
      biloma may be related to pseudoaneurysms and delayed hemorrhage in severe hepatic
      injury.

PMID- 8131172
TI  - Balloon dilatation and stent placement of suprahepatic caval anastomotic stenosis
      following liver transplantation.
AB  - We present an unusual case of suprahepatic caval anastomotic stenosis after adult
      liver transplantation in the early postoperative period. Color flow Doppler
      sonography and cavography were used to confirm the clinical diagnosis. Successful
      nonoperative treatment of the obstruction was achieved by balloon dilatation and
      subsequent implantation of a vascular stent.

PMID- 8131173
TI  - Left pulmonary artery sling in the adult: case report and review of the
      literature.
AB  - The aberrant left pulmonary artery is a serious anomaly in neonates; in the adult
      it is most often an incidental finding. One case is reported, incidentally
      discovered in the diagnostic workup of a patient with a vertebral lytic lesion.
      This vascular anomaly, mimicking a mediastinal adenopathy on the chest
      roentgenogram, which also showed a peripheral lung malignancy, was better
      assessed by an esophagogram (indentation on the posterior tracheal wall as well
      as on the anterior esophageal wall) along with fluoroscopy which showed the
      lesion to be pulsating. Its thorough anatomic evaluation was allowed by computed
      tomography (CT), performed for the staging of the lung tumor. The latter proves
      the choice modality due to its capability to provide precise information on all
      the different structures existing in a given cross-section.

PMID- 8131174
TI  - Selective intraarterial chemotherapy of tumors in the lingual artery territory by
      a new approach.
AB  - Selective intraarterial neoadjuvant chemotherapy of carcinoma in the region of
      the lingual artery was performed in 23 patients (bilaterally in 4 patients). The
      superficial temporal artery (STA) was surgically exposed and a preshaped infusion
      catheter was inserted. The catheter tip was maneuvered through the STA into the
      lingual artery under fluoroscopic guidance. Two combinations of cytostatic agents
      were then continually infused through the catheter for 5-9 days. Treatment
      response was observed in 16 patients, 9 of whom showed a complete response. The
      combination of cisplatin and 5-fluorouracil was found most effective. The
      catheter became dislocated six times among 27 catheterizations and in each
      instance the position could be corrected. No major complications were
      encountered. We conclude that selective infusion technique is safer than
      previously reported semiselective infusions techniques.

PMID- 8131175
TI  - Re: Selecting the right technique to reform a reverse curve catheter (Simmons
      style): critical review.

PMID- 8131176
TI  - [The nation and health care].
AB  - In many countries at present reforms of the health services are underway. Their
      common feature is an attempt to resolve in an optimal way the relationship of the
      State to health care and to define its regulatory role in relation to the health
      services. Health care in the Czech Republic is facing a similar problem. Under
      conditions of the global political, economic and social transformation of society
      as a whole it is essential to define the character and extent of a certain state
      regulation which will suit best the specific economic, social situation and
      health status in the country. In the submitted paper the author makes some
      suggestions which may help to clarify and resolve this important and difficult
      problems. CONCLUSIONS: Health services reforms which are underway have the aim to
      resolve in an optimal way also the relationship of the State and health services.
      In the Czech Republic regulatory provisions must correspond with the socio
      economic position and with health status in the country.

PMID- 8131177
TI  - [New findings in type I diabetes].
AB  - The author present a review of contemporary views on the pathogenesis of type I
      diabetes, in particular with regard to recent research of European and non
      European diabetelogical departments. In the aetiopathogenesis attention is drawn
      to genetic influences, external factor and stimuli, the importance of some virus
      groups (Picornidae, Mengo 2T virus, Coxsackie B5, cytomegaloviruses, congenital
      rubeola syndrome etc.). Special attention is paid to the autoimmune theory of
      type I diabetes, the importance of different types of anti- beta-cell antibodies,
      insulin antibodies, antibodies against protein 64-KD of the islets, pro-insulin
      antibody PAA, and other stimuli and interferences (oxidation stress, non
      enzymatic glycosylation etc.). As to treatment, the author mentions
      immunosuppressive treatment (cyclosporin A, azathioprine, prednisone) and
      transplantation of the pancreas. The author presents his own experience with a
      group of 2040 diabetics; in a group of 253 juvenile diabetics he followed-up the
      development of micro- and macroangiopathic complications in the course of 25
      years. He proved an increase of so-called late diabetic complications in
      particular vascular ones along with the lengthening period of diabetes, with
      advancing age during its clinical manifestation. In the conclusion the author
      draws attention to the importance of multi-centre studies and new laboratory
      techniques.

PMID- 8131178
TI  - [Hyperinsulinemia--the common denominator in type II diabetes mellitus,obesity,
      hypertension, hypertriglyceridemia and atherosclerosis].
AB  - During the last twenty years we witnessed a remarkable increase in knowledge of
      the mechanism as regards insulin action, the central hormone of metabolic
      regulations. Interest in cellular and molecular mechanisms of action was
      conditioned by a high prevalence of insulin resistance and the fact that insulin
      resistance holds a key position in the pathogenesis of many diseases, in
      particular atherosclerosis, obesity, hypertension, diabetes mellitus type II,
      ovarian hyperandrogenism and others. The syndrome of hyperinsulinaemia/insulin
      resistance is the basic component of the so-called X syndrome defined in 1988 by
      Reaven. It is encountered in subjects with a normal glucose tolerance but a
      predisposition for diabetes type II. If this disposition, probably genetic by
      nature, is potentiated by the central type of obesity and a sedentary lifestyle
      it can influence the development of hypertension and dyslipidemia. The sum of
      these factors promotes acceleration of atherosclerosis and frequently its
      premature manifestations: myocardial infarction and other cardiovascular diseases
      which hold the first place as regards causes of death on a world wide scale. It
      is important to identify but also to treat this complex not only metabolic risk
      factors for macrovascular diseases. It is a paradox that some drugs used as
      antihypertensives can cause deterioration of insulin resistance, subsequently
      influence in an adverse manner dyslipidemia and thus increase the metabolic risk
      of cardiovascular diseases. In the submitted paper the authors tried to summarize
      hitherto expressed views on the syndrome of hyperinsulinaemia and insulin
      resistance, using as a basic the results of their own work.

PMID- 8131179
TI  - [Endothelins. I. Physiology].
AB  - At the beginning of 1988 in Japan in a unique manner a new peptide substance
      derived form the endothelium was described, so far the most powerful
      vasoconstrictor substance-endothelin. This started an information boom which soon
      led to evidence of other substances of this group, naturally related substances;
      the detailed structure of all endothelins was established, gradually these
      substances were synthetized, very sensitive radioassays for their estimation were
      developed. Experimental and clinical work on endothelins and their effects
      penetrate at present all spheres of medicine and intensive work is under way,
      focused on their use in the treatment of diseases as widespread as hypertension,
      vasospastic disorders, atherosclerosis, bronchial asthma, renal failure, etc.
      These findings are becoming the basis of a medical sub-discipline which can be
      described by the term of vascular wall endocrinology. In the first part of the
      review the author submits information on the chemical structure, synthesis and
      secretion of endothelins, on their plasma levels, mechanism of intracellular
      action and experimental effects. In the second part the author reviews findings
      on the participation of endothelins in the pathogenesis of cardiovascular and
      renal diseases. Their role in the control of volume homeostasis and in the
      genesis of the preeclamptic syndrome is discussed, as well as effects on the CNS
      and other organs, and the author reflects on the general impact of contemporary
      findings on endothelins in medicine and on possibilities of their perspective
      practical use.

PMID- 8131180
TI  - [Endothelins. II. Clinical findings].

PMID- 8131181
TI  - [The effect of Proglicem in patients with an organic hyperinsulinism syndrome].
AB  - BACKGROUND: Organic hyperinsulinism is treated as a rule conservatively with
      diazoxide (Proglicem) which has a hyperglycaemic effect. In some patients,
      however, treatment fails and severe hypoglycaemia persists. The objective of the
      present investigation was to find simple criteria for evaluation of the aptness
      (effectiveness) of this treatment. METHODS AND RESULTS: In 11 patients with a
      confirmed insulinoma Proglicem was administered for five days (3 mg/kg body
      weight) and serum insulin and the blood sugar level as well as their ratio
      (IRI:G) were followed-up. In eight patients the IRI/G coefficient declined from
      10.5 +/- 7.7 to 5.8 +/- 2.9 (p < 0.001); only in three patients the coefficient
      increased from 4.6 +/- 2.9 to 14.9 +/- 12.3 (p < 0.001). Coefficient "k" from the
      modified Bergman model for the intravenous glucose tolerance test had identical
      results; there was statistically significant agreement between the two
      examinations. CONCLUSIONS: To assess the effectiveness of diazoxide treatment
      (Proglicem) on hypoglycaemia in nesidiomas it is sufficient to evaluate the IRI/G
      coefficient (on fasting) before and during diazoxide treatment (Proglicem,
      Schering Corp.).

PMID- 8131182
TI  - [Spiramycin].
AB  - Spiramycin is a 16-membered ring macrolide (antibiotic). It was discovered in
      1952 as a product of Streptomyces ambofaciens. As a preparation for oral
      administration it has been used since 1955, in 1987 also the parenteral form was
      introduced into practice. The antibacterial action involves inhibition of protein
      synthesis in the bacterial cell during translocation. Resistance to spiramycin
      can develop by several mechanisms and its prevalence is to a considerable extent
      proportional to the frequency of prescription in a given area. The antibacterial
      spectrum comprises Gram-positive cocci and rods, Gram-negative cocci and also
      Legionellae, mycoplasmas, chlamydiae, some types of spirochetes, Toxoplasma
      gondii and Cryptosporidium sp., Enterobacteria, pseudomonads and pathogenic
      moulds are resistant. Its action is mainly bacteriostatic, on highly sensitive
      strains it exerts a bactericide action. As compared with erythromycin, it is in
      vitro weight for weight 5 to 20 less effective, an equipotential therapeutic dose
      is, however, only double. This difference between the effectiveness in vitro and
      in vivo is explained above all by the great affinity of spiramycin to tissues
      where it achieves concentrations many times higher than serum levels. An
      important part is played also by the slow release of the antibiotic from the
      tissue compartment, the marked action on microbes in sub-inhibition
      concentrations and the relatively long persisting post-antibiotic effect. Its
      great advantage is the exceptionally favourable tolerance-gastrointestinal and
      general. It is available for parenteral and oral administration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8131183
TI  - [Albert Schweitzer and Tomas G. Masaryk].

PMID- 8131184
TI  - Current bibliography of cell calcium prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8131185
TI  - Cell calcium, Introduction.

PMID- 8131186
TI  - Intracellular calcium waves generated by Ins(1,4,5)P3-dependent mechanisms.
AB  - Cellular oscillations of cytosolic free Ca2+ ([Ca2+]i) have been observed in many
      cell types in response to cell surface receptor agonists acting through inositol
      1,4,5-trisphosphate (InsP3). In a number of cases where appropriate spatial and
      temporal resolution have been used to examine these [Ca2+]i oscillations, they
      have been found to be organized as repetitive waves of Ca2+ increase that
      propagate through the cytosol of individual cells. In some cases Ca2+ waves also
      occur as a single pass through stimulated cells. This review discusses the
      factors underlying the spatial organization of [Ca2+]i signals in the form of
      Ca2+ waves. In addition, potential mechanisms for the initiation and subsequent
      propagation of these Ca2+ waves are described.

PMID- 8131187
TI  - Localized calcium spikes and propagating calcium waves.
AB  - Ca2+ signals control or modulate diverse cellular processes such as cell growth,
      muscle contraction, hormone secretion, and neuronal plasticity. Elevations in
      intracellular Ca2+ concentrations can be highly localized to micron and submicron
      domains or propagated as intra- and intercellular waves over distances as large
      as 1 mm. Localized, subcellular Ca2+ spikes are thought to selectively activate
      effector systems such as Ca2+ activated chloride currents in pancreatic acinar
      cells, neurotransmitter release in synaptic nerve terminals, and morphological
      changes in neural growth cones. In contrast, long-ranged Ca2+ waves synchronize
      the activities of different cytoplasmic regions of a single cell, such as
      cortical granule exocytosis after egg fertilization or coordinate the activities
      of many cells, such as ciliary beating in pulmonary epithelium. The purpose of
      this review is to delineate the role of Ca2+ in the generation of localized,
      subcellular Ca2+ spikes and long-ranged intracellular and intercellular Ca2+
      waves.

PMID- 8131188
TI  - Ca2+ signalling in exocrine acinar cells: the diffusional properties of cellular
      inositol 1,4,5-trisphosphate and its role in the release of Ca2+.
AB  - The correlation between acetylcholine induced changes in the intracellular free,
      Ca2+ concentration ([Ca2+]i), and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)
      content in isolated acini from the rat parotid and lacrimal glands was
      investigated. Applying digital image processing on Fura-2 loaded acini, we
      observed that Ca2+ increases either simultaneously throughout the acinar
      configurations or that occasionally, the rise near the lumen can precede the rise
      near the basal part by 50-100 ms. Measurements on cell suspensions revealed a
      correlation between changes in [Ca2+]i and changes in the cellular Ins(1,4,5)P3
      content, and it is concluded that in the individual cells Ins(1,4,5)P3 is
      released to the cytosol within the first second after stimulation. Applying a
      diffusion coefficient for cytoplasmic Ins(1,4,5)P3 of 2.83 x 10(-6) cm2/s
      (Allbritton et al., 1992, Science, 258, 1812-1815), we have calculated the
      concentration profile for this messenger in a sphere with a radius of 10 microns
      where Ins(1,4,5)P3 is released in the center following a monoexponential function
      with a rate constant of 4 s-1. Assuming that Ins(1,4,5)P3 concentrations of 1 or
      5% of the maximum value is able to release Ca2+, we calculated that Ca2+ waves
      can appear at a rate of 100 or 40 microns/s. The present data are consistent with
      Ins(1,4,5)P3 being a cellular messenger, that by diffusion, initiates the Ca2+
      release from the cellular pools within the first fraction of a second.

PMID- 8131189
TI  - Mechanisms of calcium release and propagation in cardiac cells. Do studies with
      confocal microscopy add to our understanding?
AB  - Laser-scanning confocal microscopy (LSCM) has a number of recognised advantages
      over other techniques of light microscopy for the study of cell and tissue
      structure. These include increased image spatial resolution, and even more
      importantly, removal of out-of-focus information from 2-dimensional images of 3
      dimensional structures. Moreover, these features have also recently proved to be
      of immense benefit when coupled with ion-sensitive fluorescent probes, in the
      study of second messenger systems in relation to cell function. This review
      summarises the contribution that recent studies with LSCM have made to our
      understanding of the important patho-physiological state, spontaneous Ca(2+)
      release (SCR) in isolated cardiac myocytes, and the relationship of this
      phenomenon to the induction of abnormal cell automaticity or cardiac arrhythmia.
      In some components of SCR and propagation, our existing knowledge has only been
      confirmed by recent results, while in others facets of this complex process, our
      understanding is being greatly enhanced by LSCM.

PMID- 8131190
TI  - Classes and mechanisms of calcium waves.
AB  - The best known calcium waves move at about 5-30 microns/s (at 20 degrees C) and
      will be called fast waves to distinguish them from slow (contractile) ones which
      move at 0.1-1 microns/s as well as electrically propagated, ultrafast ones. Fast
      waves move deep within cells and seem to underlie most calcium signals. Their
      velocity and hence mechanism has been remarkably conserved among all or almost
      all eukaryotic cells. In fully active (but not overstimulated) cells of all
      sorts, their mean speeds lie between about 15-30 microns/s at 20 degrees C. Their
      amplitudes usually lie between 3-30 microM and their frequencies from one per 10
      300 s. They are propagated by a reaction diffusion mechanism governed by the
      Luther equation in which Ca2+ ions are the only diffusing propagators, and
      calcium induced calcium release, or CICR, the only reaction; although this
      reaction traverses various channels which are generally modulated by IP3 or
      cADPR. However, they may be generally initiated by a second, lumenal mode of CICR
      which occurs within the ER. Moreover, they are propagated between cells by a
      variety of mechanisms. Slow intracellular waves, on the other hand, may be
      mechanically propagated via stretch sensitive calcium channels.

PMID- 8131191
TI  - Ca2+ oscillations in pancreatic acinar cells: spatiotemporal relationships and
      functional implications.
AB  - The pancreatic acinar cells are of particular interest for the study of cytosolic
      Ca2+ signals, since they are morphologically polarized and generate agonist
      specific Ca2+ oscillation patterns. Recent data obtained by combining digital
      video imaging of Fura-2 fluorescence with patch-clamp whole-cell current
      recording have provided new information on the spatiotemporal relationships of
      the cytosolic Ca2+ signals and the Ca(2+)-activated ionic currents. Low agonist
      concentrations evoke repetitive short-lasting local Ca2+ spikes in the secretory
      pole region that activate shortlasting current spikes. In the case of
      acetylcholine stimulation the spikes are confined to this region. When
      cholecystokinin is used the shortlasting local spikes precede longer Ca2+
      transients that spread to the whole of the cell. Infusion of non-metabolizable
      inositol trisphosphate analogues can mimic these responses. The shortlasting
      local Ca2+ spikes are particularly sensitive to blockade by the inositol
      trisphosphate receptor antagonist heparin. These results show that the secretory
      pole region has a particularly high sensitivity to inositol trisphosphate
      probably due to clustering of high affinity receptors.

PMID- 8131192
TI  - Haemoglobin A2 (Hb A2) and malaria.
AB  - The Packed Cell Volume (PCV), reticulocyte count and Hb A2 were determined in 28
      patients during the period of malaria parasitaemia and 14 days after effective
      treatment. The Hb A2 was determined by cellulose acetate haemoglobin
      electrophoresis in alkaline medium followed by elution in water. There was no
      statistically significant difference between the PCV during the period of
      parasitaemia and that after treatment (p > 0.05). The Hb A2 level did not show
      any significant difference during and after treatment of malaria (p = 0.05). The
      correlation coefficient between absolute parasite count and Hb A2 level was -0.22
      (p = 0.251). It is concluded that malaria parasitaemia does not induce a
      significant change in the level of Hb A2.

PMID- 8131193
TI  - Trisomy 18-Edwards syndrome: a report of three patients.

PMID- 8131194
TI  - Laparoscopic cholecystectomy in Zimbabwe: initial report.
AB  - The laparoscopic approach has become the preferred technique of doing
      cholecystectomy in many parts of the world. In our initial experience with 19
      patients we had no mortalities and no major complications. The average hospital
      stay was 2.9 days with all patients returning to normal activities seven days
      after discharge. Sixteen pc of cases were converted to open cholecystectomy due
      to difficulties in defining the anatomy. The mean operating time was 159 minutes.
      We believe that laparoscopic cholecystectomy can be performed safely and that it
      does offer advantages to many patients.

PMID- 8131195
TI  - Disease pattern and prescribing at the University of Zimbabwe students health
      service, 1987-1991.
AB  - The trends in drug use, expenditure and disease pattern at the University of
      Zimbabwe students' health facility over a period of five years (1987-1991), were
      analysed retrospectively. The study also analysed the use of the essential drugs
      concept and the drug situation in Zimbabwe. A total of 1,500 cases which were
      randomly selected were studied. The total student population over this period was
      44,030. Data collection sheets where utilised to extract information from
      patients' cards. Requisition order books and budgets for drugs and medical
      appliances and student population statistical data were analysed. Males accounted
      for 75.7 pc of the cases and the average age at the time of the visit was 22.04
      years. The percentage of cases involving married students was 2.53 pc of which
      94.74 pc were males. The total expenditure of drugs and medical appliances for
      the study period was $412,413.55 and most of the items were supplied by the
      Government Medical Stores. The most prevalent disease conditions were respiratory
      tract infections (35 pc) and urinary tract infections (16.3 pc). The disease
      pattern differed from that at district, general and provincial hospitals. The
      total number of drugs dispensed for the 1,500 students was 2,600, giving an
      average of 1.7 drugs per case. Analgesics were the most widely used drugs (28.5
      pc), followed by anti-infectives (28.2 pc). The most popular analgesic used was
      paracetamol which accounted for 66.6 pc of the analgesics. Antibiotics accounted
      for 88.1 pc of the anti-infectives and 24.9 pc of the total number of drugs
      dispensed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131196
TI  - Knowledge, attitudes and practices of mothers and health workers in relation to
      the use of sugar and salt solution in Masvingo Province, Zimbabwe.
AB  - A study was carried out (March-April 1992) in the rural, urban and farming areas
      of Masvingo Province in Zimbabwe to assess the knowledge, attitudes and practices
      of mothers and health workers on the use of sugar-salt solution. Twenty mothers
      from each area were also asked to prepare sugar-salt solution and the solutions
      were analysed for sodium and sucrose content. A total of 257 mothers out of 300
      knew of the sugar-salt solution. Of these 58 pc from rural, 40 pc from urban and
      63 pc from farming areas, said that they gave sugar-salt solution as the first
      line of action in managing diarrhoea. Mothers were not exactly sure of the
      amounts of sugar-salt solution to give the child with diarrhoea. Responses ranged
      from a mere three teaspoons per day, to cupfuls and bottle capfuls although the
      majority (60 pc from rural areas, 72 pc from urban areas and 77 pc from farming
      areas) claimed that they gave the whole 750ml bottle of the solution per day. The
      commonest response on the frequency of administering the SSS was "after every
      loose stool" which was mentioned by 30 pc of the mothers in the rural areas, 35
      pc in the urban areas and 54 pc in the farming areas. Recall of the standard
      method of preparation of sugar-salt solution was good for the majority of mothers
      in all the three areas but the mean sodium concentration of the solutions
      prepared by mothers in the rural, urban and farming areas were 20.56 mmol/litre,
      19.76 mmol/litre and 39.62 mmol/litre respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8131197
TI  - Salmonella and shigella bacteraemia in Zimbabwe.
AB  - In patients with HIV infection, non-typhoidal salmonellae are a recognised cause
      of bacteraemia. This association was initially demonstrated in the United States,
      but has more recently been found in Kenyan patients. This prompted us to review
      the cases of patients with enterobacteriaceae bacteraemia admitted to
      Parirenyatwa Hospital, Harare. Non-typhoidal salmonella bacteraemia as compared
      with typhoid fever was significantly more common in HIV infected patients than in
      non-HIV infected patients (p < 0.01). It was also a cause of bacteraemia in
      patients with other immuno-suppressive conditions and in some patients without
      identifiable risk factors.

PMID- 8131198
TI  - The pattern of medical illness in a community of elderly Nigerians.
AB  - A community survey of Nigerians aged 60 years and above was carried out. Nine
      hundred and fifty one subjects were interviewed by trained nurses. Seven hundred
      and fifty nine (79pc) had physical examination carried out on them. It was found
      that musculoskeletal, dental, ocular and cardiovascular disorders were the
      commonest problems in this group of people. Poor dental hygiene, anaemia and
      goitre were problems significantly associated with living in rural areas, while
      hypertension was commoner in urban areas, but this did not reach significance at
      five pc level. The results show that about one out of five elderly Nigerians
      suffer from chronic disabling conditions such as osteoarthritis and 2.4pc of them
      were diabetic. The impact of these chronic diseases on the health of the elderly
      Nigerians is discussed and suggestions made for health promotion interventions
      and treatment programmes.

PMID- 8131199
TI  - Hot, high and horrible. Should routine enemas still be given to women in labour?
AB  - The effect of a soap enema on the progress of labour was studied in 160 women
      admitted for delivery in Esigodini District Hospital. The study was set up as a
      1:1 randomised case control study in 200 women. It was changed to a 1:3 case
      control study after 82 subjects had been studied, when it became apparent that
      the midwives were no longer willing to follow the study protocol. Forty women
      received an enema and 120 did not. Two focus group discussions were held with 16
      women who had an enema. The 12 hospital midwives were asked to give their opinion
      on enemas. Focus group discussions were also held with 28 traditional midwives.
      Dilation of the cervix was 2.19 cm/hour in the non-enema group (95pc confidence
      interval 1.86-2.52) and 2.00 cm/hour in the enema group (95pc confidence interval
      1.38-2.62). The difference is not significant (t-test:p-value = 0.58). Pregnant
      women did not like enemas, midwives preferred not to administer them and were not
      concerned with contamination during delivery. Traditional midwives do not use
      enemas in labouring women and consider the possible contamination as normal. It
      is concluded that there is no benefit from routine enemas in labour.

PMID- 8131200
TI  - Peripheral nerve injuries in a Third World country.
AB  - This five year prospective research study reports on 74 patients with injuries to
      89 nerve segments. Ninety eight pc of the injuries were caused by penetrating and
      only four pc by blunt trauma; 5.4 pc of the patients presented directly to use as
      emergencies while the remainder presented after an average delay of 23 weeks.
      Clavioaxillary (40.5 pc) and upper limb (41.9 pc) neurological lesions
      constituted the bulk of the injuries involving a predominantly younger male
      population (96 pc). Brachial plexus and proximal upper limb injuries often
      involved more than one segment of a nerve, 34.9 pc of the lesions were
      axonotmetic, requiring external and internal neurolyses, while 65.1 pc were
      neurotmetic, for which neurorrhaphy (in four patients) or sural nerve
      interposition grafting was performed. The follow up compliance was poor. At two
      years, with a 55.4 pc re-attendance rate, improvement to at least grade three or
      more, was achieved in 50 pc of the attending patients, neurolysed for axonotmesis
      and in 53.8 pc of the neurotmetic patients who required sural grafts. At five
      years the re-attendance rate had fallen to 16.2 pc and this did not offer a
      realistic clinical and statistical generalisation of the results.

PMID- 8131201
TI  - Cholecysto-choledochal fistula--Mirizzi syndrome (type II) in a Nigerian.
AB  - Mirizzi syndrome is an uncommon cause of obstructive jaundice in which the common
      hepatic duct is obstructed by stones trapped within the neck of the cystic duct
      of the gall-bladder. In long standing cases the calculi may erode through into
      the common duct and may in fact, impact in the resulting fistula. This syndrome
      with its later progression is a rare complication of calculous disease of the
      gall-bladder worldwide. While it is perhaps encountered in the developing
      countries where cholelithiasis is not as prevalent as in the affluent countries,
      there has not been much documentation. This article reports on a Nigerian patient
      with a fistulous complication of Mirizzi syndrome (Type II) managed by
      cholecystectomy and choledochoduodenostomy and also presents a discussion of the
      condition.

PMID- 8131202
TI  - Dupuytren's contracture in black Zimbabweans.
AB  - Four cases of Dupuytren's contracture treated at Mpilo Central Hospital over the
      last 13 years are presented. Three of these patients were men aged 45, 59 and 74
      years. Only one woman aged 55 years was treated during this period. All the four
      patients were indigenous Black Zimbabweans. There was some history of trauma to
      the affected upper limb in all three of the male patients and all of them agreed
      to being moderate smokers but only two gave a history of drinking alcohol. One of
      the men had been treated for pulmonary tuberculosis. The female patient has been
      on treatment for epilepsy for more than 10 years. There was no family history of
      Dupuytren's contracture in any of these patients. Although Dupuytren's
      contracture is generally considered to be a European disease this report and a
      few isolated case reports confirm that this condition occurs in indigenous Black
      Africans.

PMID- 8131203
TI  - IFN-gamma stimulates IgG2 production from bovine B cells costimulated with anti
      mu and mitogen.
AB  - The effect of interferon-gamma (IFN-gamma) antibody production by anti-mu- or
      pokeweed mitogen-stimulated bovine B cells was studied. IFN-gamma induced IgG2
      secretion in isolated bulk B cell populations and in B cells sorted for IgM
      expression. IgM production was suppressed by the presence of IFN-gamma alone but
      this effect was antagonized by interleukin 2 (IL2). The effects of IFN-gamma on
      secreted levels of IgM, IgG1, and IgG2 correlated with the frequencies of cells
      expressing transcripts of the respective isotypes when stimulated with IFN-gamma
      containing T cell supernatants. These results indicate that IFN-gamma plays a key
      role in IgG2 production in the bovine by directly affecting suitably stimulated B
      cells. The ability of IL2 to synergize with IFN-gamma to augment both the IgM and
      IgG2 responses implicates a TH1-like subset in regulation of this isotype.

PMID- 8131204
TI  - Prostaglandin E2 inhibits B lymphocyte activation by a cAMP-dependent mechanism:
      PGE-inducible regulatory proteins.
AB  - We have previously shown that macrophage-secreted prostaglandins of the E series
      (PGE) and other agents which increase cAMP inhibit IgM production and
      proliferation of murine B lymphocytes. In this study, we show that PGE2 inhibits
      B cell activation events including enlargement, class II MHC hyperexpression, and
      the expression of the low-affinity receptor for IgE, Fc epsilon RII/CD23 (35-50%)
      in a cAMP-dependent manner. PGE action is mimicked by other cAMP-inducing agents
      and is inhibited by RpcAMP (a nonhydrolyzable cAMP analog which is a competitive
      inhibitor of cAMP-dependent protein kinase A). PGE2 could inhibit enlargement and
      upregulation of activation Ag even if preincubated with cells and then washed out
      prior to B cell stimulation. This change in B cell phenotype was abrogated if the
      reversible protein synthesis inhibitor cycloheximide was included during B cell
      incubation with PGE2. To identify the newly synthesized cAMP- and PGE-inducible
      regulatory proteins (PIRP), two-dimensional gel electrophoresis of lysates of B
      lymphocytes treated +/- PGE2 was performed. This report is the first to identify
      putative PIRP proteins. The roles of PIRP in PGE regulation of B cell activation
      and class switching are discussed.

PMID- 8131205
TI  - Quantitative analysis of the B cell repertoire by limiting dilution analysis and
      fluorescent in situ hybridization.
AB  - We have made a quantitative and concurrent analysis of B cell frequencies and VH
      gene family expression to study the influence of tissue type and age on the
      development and establishment of the primary B cell repertoire. Using LPS
      mediated limiting dilution analysis and a panel of antigens we show that the
      newly generated B cell specificities from bone marrow get distributed without a
      bias to peripheral tissues such as spleen and Peyer's patches throughout the
      lifetime of the animal. Comparison of the B cell frequencies in animals of four
      different age groups (2-4 days old, 3, 12, and 18 months old) reveals that while
      the neonatal repertoire is comparable to that of adults, there was a selective
      twofold increase in the generation and distribution of B cells reactive with
      autologous mouse red blood cells in older mice compared to young ones. By means
      of a novel technique that employs fluorescent in situ hybridization and flow
      cytometry, we have also compared the VH gene family usage in large numbers of
      single B cells from these mice. Analysis of the same cell population (surface
      Ig+, functional B lineage cells) for expression of 7183, J558, and S107 VH
      families shows a preferential twofold increase in the use of VH 7183 in neonates
      compared to adults, while all three families show no significant difference in
      levels of expression during adult life or between primary and secondary lymphoid
      tissues. Taken together, our data indicate that specific and selective changes
      occur in both VH gene usage and antibody frequencies during murine ontogeny.

PMID- 8131206
TI  - A novel multilineage cell-surface antigen expressed on terminally differentiated
      chicken B cells in mucosal tissues.
AB  - A murine monoclonal antibody, 5M19, produced to a cell line transformed by an
      avian myeloblastosis virus, detects an antigen, designated chL5, that is
      expressed on multiple lineages of hematopoietic cells from noninfected chickens.
      Immunochemical analysis demonstrated the chL5 antigen to be a homodimer of two
      disulfide-bonded chains each having an apparent molecular weight of 128,000. The
      highest level of expression was found on myelomonocytic cells, including
      granulocytes, monocytes, and macrophages, as well as on activated T lymphocytes
      and plasma cells in mucosal tissues. A low level of chL5 expression is detectable
      on T lymphocytes in the thymus and peripheral tissues of juvenile chickens, and
      mitogen activation of T lymphocytes results in a twofold increase in antigen
      expression. By Day 15 of embryonic development chL5 is expressed by a small
      population (12%) of yolk sac cells and by the majority of mononuclear cells in
      the thymus, bone marrow, and spleen. Also, chL5+ cells populate the embryonic
      bursa of Fabricius before the appearance of IgM+ B lymphocytes. A novel
      characteristic of this antigen is its expression on about 50% of plasma cells in
      the mucosal tissues of the Harderian gland and cecal tonsils while present on
      only 3-11% of circulating B cells and less than 2% of splenic plasma cells.
      Immature B lymphocytes are negative for chL5 expression. Mitogen-induced
      activation and differentiation of peripheral B cells does not alter the
      percentage of chL5+ B cells. This antigen, therefore, is a useful marker for the
      analysis of terminal differentiation of B lymphocytes. The cell distribution of
      chL5 and the correlation of expression with cell aggregation in vitro suggests
      that the antigen may be involved in cell adhesion.

PMID- 8131207
TI  - Tumor growth alters T cell and macrophage production of and responsiveness to
      granulocyte-macrophage colony-stimulating factor: partial dysregulation through
      interleukin-10.
AB  - Tumor growth induces phenotypic and functional changes among splenic T cells and
      macrophages (M phi) that contribute to the immunosuppression observed in tumor
      bearing hosts (TBH). These changes partly arise through alterations in immune
      cell production of and responsiveness to cytokines. Granulocyte-macrophage colony
      stimulating factor (GM-CSF) is an important T cell- and M phi-derived cytokine
      that is produced during normal host immunogenic challenge, but it's involvement
      during cancer is poorly defined. In contrast, interleukin-10 (IL-10) is an
      inhibitory cytokine that is produced by immune cells as a deactivation factor. IL
      10 can disrupt GM-CSF synthesis and may be associated with tumor-induced changes
      in cytokine synthesis. We determined if tumor growth alters T-cell and M phi
      synthesis of and responsiveness to GM-CSF, and if these alterations occur because
      tumor growth heightens immune cell sensitivity to IL-10. Tumor growth
      significantly decreased T-cell synthesis of GM-CSF during activation by
      concanavalin A, and TBH T cells were more susceptible to GM-CSF synthesis
      inhibition by IL-10 than their normal host (NH) counterparts. This suppression
      was observed using both unseparated splenic lymphocyte preparations and purified
      CD4+ and CD8+ T cells. Similarly, TBH M phi (both splenic and peritoneal)
      produced less GM-CSF than NH M phi during activation by lipopolysaccharide. Tumor
      growth also altered major histocompatibility complex (MHC) class II- M phi GM-CSF
      synthesis. TBH M phi were more susceptible to GM-CSF synthesis inhibition by IL
      10 than their NH counterparts. Although TBH T cells demonstrate less
      proliferation than NH T cells during activation, tumor growth did not compromise
      T-cell responsiveness to GM-CSF. However, tumor growth did increase TBH T-cell
      susceptibility to inhibition of proliferation by IL-10. Tumor growth suppressed M
      phi responsiveness to GM-CSF, and IL-10 further decreased M phi responsiveness to
      GM-CSF. Collectively, these results suggest that T cell and M phi production of
      and responsiveness to GM-CSF is disrupted during tumor growth, and that TBH T
      cells and M phi are more susceptible to the suppressor activity of IL-10 than
      their NH counterparts.

PMID- 8131208
TI  - Transformed B cell lines express cell-associated tumor necrosis factor and
      mediate natural cytotoxic activity.
AB  - Natural cytotoxic (NC) activity is mediated by a cell-associated form of TNF
      alpha. Here, we have characterized the NC-like properties of cloned murine
      transformed B cell lines. Several B cell lines cause the lysis of NC/TNF-alpha
      susceptible target cells, but not NC/TNF-apha-resistant target cells.
      Furthermore, lysis of targets by B cell lines involves a nonsoluble (i.e., cell
      associated) mechanism that is blocked by anti-TNF antibody. Target cells selected
      for resistance to a B lymphoma cell line expressing NC-like activity are
      resistant to splenic NC-mediated lysis, resistant to TNF-alpha-mediated lysis,
      and have increased tumorigenicity in BALB/c mice. Thus, these B cells lines may
      serve as cloned effectors which lyse cells using a cell-associated TNF-dependent
      mechanism analogous to NC lysis. Furthermore, it is possible that the expression
      of TNF by transformed B cells is autostimulatory and is involved in their
      malignant transformation.

PMID- 8131209
TI  - Human renal cell carcinoma cells are sensitive to the cytotoxic effect of a
      chimeric protein composed of human interleukin-4 and Pseudomonas exotoxin.
AB  - We have previously demonstrated that functional high-affinity interleukin-4
      receptors (IL-4R) are expressed on human renal cell carcinoma (RCC) cells (N. I.
      Obiri et al., J. Clin. Invest. 91, 88, 1993). In the present study, we examined
      the cytotoxic effect (determined by inhibition of protein synthesis) of a
      chimeric protein composed of human IL-4 and Pseudomonas exotoxin (PE) on human
      RCC tumor samples obtained from patients undergoing nephrectomy. The chimeric
      gene encoding hIL4-PE4E was constructed by fusing a cDNA clone for human IL-4 to
      the 5' end of a mutated cDNA encoding a full-length PE molecule. This gene was
      expressed in Escherichia coli, and large quantities of this recombinant protein
      were isolated to more than 95% purity. This chimeric protein, hIL4-PE4E, was
      highly cytotoxic to all six RCC cell lines examined. The concentration of hIL4
      PE4E at which 50% inhibition of protein synthesis was obtained ranged from < 1
      ng/ml (12 pM) to 10 ng/ml (120 pM) in five of the six isolates of RCC and 40-70
      ng/ml in one other. A mutant chimeric protein which can bind to IL-4R but lacks
      the ADP ribosylation activity of PE was not cytotoxic to the RCC cells. The
      cytotoxic effect of hIL4-PE4E was IL-4R mediated because a fourfold molar excess
      of IL-4 abrogated the cytotoxic effect of hIL4-PE4E. A neutralizing monoclonal
      antibody to IL-4 also abrogated the cytotoxic effect of hIL4-PE4E. hIL4-PE4E
      showed very little cytotoxic activity to a normal human umbilical vein
      endothelial cell line (ID50 = 1000 ng/ml) and a human fibroblast cell line (ID50
      approximately 400 ng/ml). Nonactivated human peripheral blood lymphocytes (PBL)
      were also insensitive to hIL4-PE4E (ID50, approximately 500 ng/ml), whereas
      phytohemagglutinin-activated PBL were highly susceptible to the cytotoxic effect
      of hIL4-PE4E (ID50, approximately 4 ng/ml). These data indicate that hIL4-PE4E
      may be a useful agent for the treatment of human RCC without affecting normal and
      resting immune cells.

PMID- 8131210
TI  - Isolation of lysozyme-specific T cell clones that discriminate between native and
      denatured antigen.
AB  - Hen egg white lysozyme (HEL)-specific T cell lines and clones were generated from
      B6 and BDF1 mice. A variety of clonotypes were found among clones generated at an
      early stage (1 month) whereas fewer clonotypes were detected after several weeks
      of culture. Furthermore, a bulk line switched from its initial fine peptide
      specificity pattern (positive for fragment L2--aa. 13-105--and negative for
      fragment NC--aa. 1-17:Cys 6-Cys 127:120-129) to the opposite pattern (negative
      for L2 and positive for NC), indicating that in bulk lines, besides selection
      toward oligo- or monospecificity, clones previously silent can emerge after a
      period of time. Irrespective of early or late cloning, T cell clones could be
      isolated from three independent T cell lines from different mouse strains that
      were stimulated by either native or denatured HEL, but not both. Furthermore, 1
      clone of 20 from a B6 line, 3 clones of 25 from a BDF1 line, and 1 T hybridoma
      clone of 10 of B10.A origin lost their capacity to respond to native HEL, yet
      continued to respond to reduced, carboxymethylated HEL or cyanogen bromide
      cleaved, unreduced HEL. These results suggest that T cells may produce activation
      signals for efficient processing of native antigen.

PMID- 8131211
TI  - Parotin subunit as a potent polyclonal B cell activator binds to newly found
      glycosylphosphatidylinositol (GPI)-anchored proteins on human B cell surfaces.
AB  - Parotin subunit (PS) is a unique glycoprotein, isolated from bovine parotid
      glands, which possesses the ability to induce polyclonal antibody production and
      IL-1-like activity. The present studies investigated the existence of receptors
      for PS on B cell surfaces using PS-affinity chromatography. No PS-binding
      proteins (PSR) solubilized from human B cell surfaces with Triton X-100 were
      detected, whereas the PSR released from human B cell membranes with
      phosphatidylinositol-specific phospholipase C (PI-PLC) treatment were composed of
      75- and 40-kDa proteins. PI-PLC treatment markedly reduced polyclonal antibody
      responses to PS but weakly inhibited the responses to PWM, xanthan gum, and LPS
      in human and mouse lymphocytes. Addition of PSR caused a dose-related reduction
      in polyclonal IgM and IgG antibody responses to PS. These results suggest that
      PSR can act as glycosylphosphatidylinositol-anchored receptors for PS.

PMID- 8131212
TI  - Early activation and cell trafficking induced by staphylococcal enterotoxin B:
      effects of high- versus low-dose challenge on induction of anergy.
AB  - The in vivo challenge with exogenous superantigen, staphylococcal enterotoxin B
      (SEB), selectively induces vigorous polyclonal proliferation of T cells bearing
      the V beta 8+ TcR domain, whereafter the responsive cells become anergic. We used
      kinetic analyses to compare the effects of primary (1 degree) and secondary (2
      degrees) challenge with a high and a low dose of SEB and the conventional
      antigen, sperm whale myoglobin, to determine the differential effects of in vivo
      challenge with a superantigen compared with a conventional antigen. We
      demonstrate that SEB induces very early activation-associated intralymphatic
      proliferation and trafficking of more T cells than can be accounted for by V beta
      8+ T cells alone. Overall, this study indicates that challenge with SEB causes an
      apparent loss of CD4+ T-helper cell function and provides an essential foundation
      for the understanding of the mechanisms of peripheral tolerance induction and T
      cell "memory."

PMID- 8131213
TI  - TNF induction of EL4 hyposensitivity to lysis by recombinant (soluble) and
      membrane-associated TNFs: TNF binding, internalization, and degradation.
AB  - EL4 mouse thymoma cells sensitive to TNF-mediated lysis only in the presence of
      cycloheximide (S-EL4) or in the presence or absence of cycloheximide (N-EL4) were
      used in these experiments. Murine tumor cell line (S-EL4) sensitivity to TNF
      cytotoxicity is augmented when cycloheximide is added together with TNF or when
      cycloheximide is added 1 hr before or after TNF. No enhanced sensitivity is
      observed when target cells are incubated with cycloheximide 2-4 hr before or
      after the addition of TNF. In the absence of cycloheximide, S-EL4 cells
      preexposed to murine TNF are less susceptible to lysis by TNF and TNF receptor
      conjugated TNF but are lysed by integral membrane TNF. TNF-induced
      hyposensitivity is partially reversed by actinomycin D or by culturing the
      preexposed cells for 4 hr prior to TNF lytic assay. TNF preincubation of N- and S
      EL4 cells results in an immediate decrease in 125I-TNF binding due to TNF
      receptor occupancy. Recovery of TNF-R occupancy and TNF internalization were
      subsequently noted.

PMID- 8131214
TI  - In vitro modulation of T-cell surface molecules by iron.
AB  - Iron and zinc are known to have immunomodulatory functions. In the present work,
      iron (FeC6H5O7) and zinc (ZnCl2) were tested in comparison to nickel (NiCl2) and
      cobalt (CoCl2) for their effect on six different surface molecules known to be
      involved in recognition and activation processes, namely CD4, CD2, CD3, CD8, HLA
      ABC, and HLA-DR. Iron was seen to down-modulate expression of the CD4 and the CD2
      molecules on the surface of T-lymphocytes, as indicated by a decrease in the mean
      fluorescence intensity measured by FACS analysis. None of the other T-cell
      molecules tested were significantly affected. In addition, the iron-mediated CD4
      down-modulation reached its lowest level by 12 hr, at which time a striking
      decrease in the percentage of CD4+, but not CD8+, cells was observed. This
      decrease was followed by a gradual recovery starting at 18 hr and reaching its
      highest level at 48 hr. When cells were treated with other metal salts, none of
      those effects were observed. The present results suggest that iron may play a
      regulatory role in processes of T-cell recognition and T-cell activation by
      selectively down-modulating T-cell molecules known to be involved in these
      processes.

PMID- 8131215
TI  - Influence of various compounds on the degradation of hyaluronic acid by a
      myeloperoxidase system.
AB  - Myeloperoxidase in the presence of 0.7 mM hydrogen peroxide degrades hyaluronic
      by a mechanism which involves iron. Degradation is enhanced in the presence of
      chloride ion, which is attributed to the formation of hypochlorous acid.
      Myeloperoxidase-dependent degradation of hyaluronic acid is inhibited by
      superoxide dismutase, desferrioxamine, iodide ion, bromide ion, mannitol,
      histidine and various antiinflammatory agents. The destructing agent is
      presumably the hydroxyl radical.

PMID- 8131216
TI  - Interaction of trichloromethyl free radicals with thymine in a model system: a
      mass spectrometric study.
AB  - In previous studies from our laboratory we found that the CCl4 reactive
      metabolites produced during enzymatic in vitro or in vivo CCl4 biotransformation
      covalently bind to DNA. Further, chemically produced.CCl3 produce many adducts of
      unknown structure with the four DNA bases when the reaction proceeds in model
      systems. In the present work, we describe our attempt to elucidate by GLC/MS the
      structures of the adducts resulting when chemically generated.CCl3 interact with
      thymine. The following reaction products were identified: (i) 5-hydroxymethyl
      uracil; (ii) thymineglycol; (iii) 5-trichloroethyl uracil (tentative) and (iv)
      two isomeric 5,6-monochloro monohydroxy adducts of thymine (tentative). Reaction
      products found do not involve thymine positions directly participating in base
      pairing processes. However, alterations in thymine structure reported if they
      occurred in DNA from livers of CCl4 poisoned animals, might potentially have
      biological significance that remains to be established.

PMID- 8131217
TI  - Mitochondrial formation of beta-oxopropyl metabolites from bladder carcinogenic
      omega-carboxyalkylnitrosamines.
AB  - Certain environmentally relevant nitrosamines specifically induce malignant
      tumors in the urinary bladder in several animal species. For this organotropic
      effect, formation of omega-carboxylated proximal metabolites has been found to be
      obligatory. The mechanism of action of these intermediates, however, is not yet
      clear. We investigated biotransformation of butyl-3-carboxypropylnitrosamine
      (CAS: 38252-74-3), methyl-3-carboxypropylnitrosamine (CAS: 61445-55-4) and methyl
      5-carboxypentylnitrosamine by mitochondrial fractions from rat liver and renal
      cortex. On incubation with mitochondrial fractions, the respective beta-oxidized
      metabolites butyl-2-oxopropylnitrosamine (CAS: 51938-15-9) or methyl-2
      oxopropylnitrosamine (CAS: 55984-51-51) were formed. This biotransformation was
      ATP dependent, associated with the presence of mitochondrial marker enzyme
      (cytochrome c oxidase) in 7000 x g subfractions and was inhibited by octanoic
      acid. Highest metabolic rates were observed with rat liver fractions. These
      results demonstrate that omega-carboxylated nitrosamines are substrates for
      mitochondrial enzymes of fatty acid degradation, most probably following the
      degradation pathway of medium-chain fatty acids. By this reaction, water-soluble
      carboxylated nitrosamines of low genotoxic potential are converted into rather
      lipophilic 2-oxopropyl metabolites with high genotoxic and carcinogenic potency.
      In contrast to carboxylated metabolites, 2-oxopropyl derivatives are good
      substrates for cytochrome P-450 dependent mono-oxygenases. Therefore,
      mitochondrial beta-oxidation appears to be an important step in metabolic
      activation of nitrosamines tumorigenic in the urinary bladder.

PMID- 8131218
TI  - Signalling by O2-. and NO.: how far can either radical, or any specific reaction
      product, transmit a message under in vivo conditions?
AB  - With regard to the stability of the NO. radical as a chemical entity, it is
      without doubt able to serve as an intra- as well as an intercellular messenger.
      The radical O2-., in contrast, does not seem to be suited to far-range signalling
      in the vascular system. Its short chemical half-life, which is limited by the
      presence of various reactive blood constituents to below 50 ms, results in a free
      diffusion path length of less than 40 microns, i.e. only the distance between
      just a few cells. While accelerated 'downstream' transport by arterial blood may
      help to extend the action sphere, there is no possibility for O2-. to serve as a
      signal in an upstream direction. The estimates presented, however, do not
      invalidate arguments for a possible role of superoxide anions in intra- or
      pericellular signalling phenomena. Cross-talk between NO.- and O2-.-dependent
      signal routes, e.g. by peroxynitrite formation, is unlikely to be a relevant
      process under the conditions which prevail in the vascular system.

PMID- 8131219
TI  - Mechanistic studies of uridine diphosphate glucuronosyltransferase.
AB  - Bisubstrate reaction kinetics and product inhibition studies were used to
      characterize the kinetic mechanism of a partially purified uridine diphosphate
      glucuronosyltransferase (UDPGT). These studies indicate that the reaction most
      likely occurs via a random order sequential mechanism. The effect of electron
      withdrawing and donating groups on the rate of reaction was also determined. It
      was found that electron donating groups increased the rate of glucuronide
      conjugation. This result is consistent with nucleophilic attack of the C-1 carbon
      of the UDP-glucuronic acid (UDPGA) by an SN2 mechanism. This is the first direct
      evidence for a SN2 mechanism in UDPGT catalysis.

PMID- 8131220
TI  - Alterations of hepatocyte Ca2+ homeostasis by triethylated lead (Et3Pb+): are
      they correlated with cytotoxicity?
AB  - Isolated rat hepatocytes were used to investigate the biochemical mechanisms of
      toxicity of triethyllead (Et3Pb+), a highly neurotoxic degradation product of the
      antiknocking petrol additive tetraethyllead. As early as 5 min from the addition
      of 50 microM Et3Pb+ to hepatocyte suspensions a decrease of mitochondrial
      membrane potential and of the capacity of mitochondria and microsomes to retain
      Ca2+ occurred. A dose-dependent release of mitochondrial Ca2+ as well as an
      inhibition of microsomal Ca(2+)-ATPase activity were also evident when Et3Pb+
      (from 2.5 microM up to 50 microM) was added to, respectively, isolated liver
      mitochondria and microsomes. Further experiments using hepatocytes loaded with
      the Ca2+ indicator Fura-2AM demonstrate that 1 min from addition of Et3Pb+ the
      cytosolic free Ca2+ levels increased by about 3-fold. High affinity plasma
      membrane Ca(2+)-ATPase activity was also significantly inhibited in hepatocytes
      treated with Et3Pb+, suggesting that an impairement of the mechanisms controlling
      the efflux of extracellular Ca2+ was concomitantly involved in the rise in
      cytosolic Ca2+ concentration. The increase in the cytosolic Ca2+ levels caused by
      Et3Pb+ was followed by a rapid decline of cell viability. However, the addition
      of EGTA or of the intracellular Ca2+ chelator BAPTA/AM did not affect either the
      time-course or the extent of cytotoxicity. Conversely, fructose, a glycolytic
      substrate that was able to support ATP production, prevented hepatocyte death.
      Thus, the depletion of cellular energy stores rather than the increase in
      cytosolic Ca2+ appears to be the mechanism by which Et3Pb+ causes irreversible
      injury in isolated hepatocytes.

PMID- 8131221
TI  - Effect of 1,1'-(2,2,2-trichloroethylidene)-bis(4-chlorobenzene) (DDT) on gap
      junctional intercellular communication and morphological transformation of Syrian
      hamster embryo cells.
AB  - The organochlorine insecticide 1,1'-(2,2,2-trichloroethylidene)bis(4
      chlorobenzene) (DDT) did not induce or promote induction of morphological
      transformation in Syrian hamster embryo (SHE) cells, but it was a potent
      inhibitor of gap junctional intercellular communication (GJIC). The kinase
      inhibitor staurosporine did not affect DDT induced inhibition of GJIC, although
      it has been shown to decrease the inhibitory effect of 12-O-tetradecanoyl-phorbol
      13-acetate (TPA) on GJIC. In addition, pretreatment with TPA made the cells
      refractory to further TPA induced inhibition of GJIC, while they remained
      sensitive to DDT. Thus, DDT and TPA inhibit GJIC through different mechanisms.
      Elevation of cellular cyclic adenosine monophosphate (cAMP) level by exposure to
      forskolin counteracted the inhibitory effect of DDT similar to that observed for
      TPA. Continuous exposure to DDT at concentrations near the effective
      concentration (50%) value (EC50 value) resulted in a slight recovery of GJIC
      following the initial inhibition. This recovery was not accompanied by the cells
      becoming refractory to further DDT induced inhibition of GJIC. The recovery of
      GJIC after removal of the DDT containing medium seemed to be related to a
      reduction in the amount of cell-associated DDT.

PMID- 8131222
TI  - Inhibition of human glutathione S-transferases by dopamine, alpha-methyldopa and
      their 5-S-glutathionyl conjugates.
AB  - The reversible and irreversible inhibition of human glutathione S-transferases
      (GST) by dopamine, alpha-methyldopa and their 5-S-glutathionyl conjugates (termed
      5-GSDA and 5-GSMDOPA, respectively) was studied using purified isoenzymes. The
      reversible inhibition, using CDNB as substrate and expressed as I50, ranged from
      0.18-0.24 (GST M1a-1a), 0.19-0.24 (GST M1b-1b) to 0.5-0.54 mM (GST A1-1) for 5
      GSDA and 5-GSMDOPA, respectively. About 20% inhibition was observed for GST A2-2
      and P1-1, using 0.5 mM of both 5-GSDA and 5-GSMDOPA. No significant reversible
      inhibition was observed with dopamine and alpha-methyldopa. Tyrosinase was used
      to generate ortho-quinones from dopamine and alpha-methyldopa which may bind
      covalently to GST and thereupon irreversibly inhibit GST. In this respect, GST P1
      1 was by far the most sensitive enzyme. The inhibition (expressed as a % of
      control) after incubating 0.5 microM GST in the presence of 100 units/ml
      tyrosinase with 5 microM of the catecholamines for 10 min at 25 degrees, was 99%
      and 67% for dopamine and alpha-methyldopa, respectively. Moderate irreversible
      inhibition of GST A1-1 by both dopamine and alpha-methyldopa (33% and 25%,
      respectively), and of GST M1b-1b by dopamine (45%) was also observed. GST P1-1 is
      also the only isoenzyme susceptible to irreversible inhibition by 5-GSDA (33%
      inhibition), while no significant inhibition was observed with 5-GSMDOPA. A minor
      part of the inhibition by dopamine (23%), and the complete inhibition by 5-GSDA
      was restored by reduction with dithiotreitol. This suggests that GST P1-1 is
      inhibited by disulfide formation in the case of 5-GSDA, while this oxidative
      pathway also substantially contributes to the inactivation by dopamine. This was
      supported by the HPLC-profile of the GST P1-1 subunit which was strongly affected
      by dopamine, while for 5-GSDA after reduction with dithiotreitol the original
      elution profile of the subunit returned.

PMID- 8131223
TI  - Rapid inhalation induction with halothane-nitrous oxide for myasthenic patients.
AB  - Rapid inhalation induction (RII) was successfully employed for patients without
      myopathy. Inhalatory agents can be used for anaesthetic induction of myasthenics,
      avoiding the use of neuromuscular blocking agents. We studied the use of RII in
      15 myasthenics (MG) and in 15 normal subjects (nMG), measuring induction time
      (TI), cardiorespiratory effects, complications, and evaluated the patient's
      reaction to RII. The patients were submitted to elective transsternal thymectomy
      (MG) and gynaecological or lower abdominal surgery (nMG). No premedication was
      used. After preoxygenation, RII was started using a mixture of 4% halothane and
      O2:N2O (1:2). They performed three vital capacity breaths, followed by normal
      spontaneous ventilation. The TI was assessed by timing the loss of verbal command
      (TLVC) and loss of eyelid reflex (TLER). Systolic and diastolic pressure, pulse
      oximetry, capnometry, respiratory rate (RR) and heart rate (HR) were measured
      during induction at each minute, for four minutes. After a postanaesthetic
      questionnaire only two normal subjects did not like the RII technique. Mean
      values for TLVC and TLER were 67 and 73 sec for MG and 64 and 69 sec for nMG,
      respectively. There was no change in HR for MG or blood pressure. The RR
      increased in both groups, but no change in PetCO2 was observed; SaO2 was > 97%.
      In conclusion, RII can be performed rapidly and safely in myasthenic patients and
      is a technique that should be considered for the induction of anaesthesia in
      myasthenic patients.

PMID- 8131224
TI  - End-tidal carbon dioxide measurement in infants and children during and after
      general anaesthesia.
AB  - We have examined the reliability of end-tidal carbon dioxide (PetCO2) monitoring
      as an estimate of arterial carbon dioxide tension (PaCO2) in spontaneously
      breathing infants and children. Forty patients were studied in the post
      anaesthetic care unit; 20 < 12 kg and 20 > or = 12 kg. The PetCO2 was sampled via
      a 5 cm 16 gauge catheter taped below an external naris and this measurement was
      compared with the PaCO2 of a sample drawn from an indwelling arterial line.
      Twenty additional patients were studied during inhalational anaesthesia. The
      PetCO2 was measured both from the proximal end of the elbow connector and from a
      5 cm cannula inserted through the elbow. An arterial blood gas sample was
      obtained simultaneously. The arterial to end-tidal (Pa-et) differences were
      compared between the two sites. Patients studied in the post-anaesthetic care
      unit showed good correlation between PetCO2 and PaCO2 regardless of weight: Pa
      etCO2 of -0.6 +/- 3.6 (< 12 kg) and -1.1 +/- 2.8 mmHg (> or = 12 kg). Patients
      studied during mask anaesthesia showed better correlation between PetCO2 and
      PaCO2 when PetCO2 was sampled from the cannula: Pa-etCO2 of 3.5 +/- 4.8 mmHg
      (cannula), 8.6 +/- 4.5 (elbow) (P < 0.05). These results suggest that end-tidal
      CO2 monitoring is a useful and reliable method for assessing adequacy of
      ventilation in spontaneously breathing children weighing between 5.2 and 35 kg.

PMID- 8131225
TI  - Mask lung ventilation by ambulance personnel: a performance assessment.
AB  - We evaluated the ability of basic life support ambulance officers and
      anaesthetists to perform lung ventilation with a face mask. After induction of
      anaesthesia and institution of standardized airway conditions the ambulance
      officer or anaesthetist placed a mask on the patient's face and lung ventilation
      was commenced. The order of hand grip (one vs two hands) was randomized. The mask
      was connected to a ventilator which had flow and pressure transducers in the
      inspiratory and expiratory breathing circuits. The output of these devices was
      sent to an electronic integrator to determine volumes. Calibration of the flow
      transducers was made against a spirometer while ventilating a test lung.
      Oesophageal insufflation was determined by listening over the epigastrium with a
      stethoscope. Data collected included presence of gastro-oesophageal insufflation,
      inspiratory and expiratory volumes. Expiratory volumes for ambulance officers and
      anaesthetists at 30 cm H2O were greater than that of ambulance officers at 20 cm
      H2O (P < 0.001) but profession of the mask holder or hand grip had no effect on
      expiratory volume. There was no difference in the mask leak when the professions
      were compared but ambulance officers had a lower mask leak with a two-handed grip
      at 20 cm H2O (P < 0.001). Anaesthetists had a greater incidence of gastro
      oesophageal insufflation when a two-handed mask grip was utilized (P < 0.05). In
      healthy relaxed patients there appeared to be little difference between the
      ambulance officers and qualified anaesthetists in airway maintenance or mask
      holding ability.

PMID- 8131226
TI  - The CAS Residents' Competition: a 25 year review.
AB  - The popularity of the Residents' Competition at the annual meeting of the
      Canadian Anaesthetists' Society inspired this 25 yr review of the competitors and
      their presentations. Data were collected from a questionnaire survey of all
      participants and all current Anaesthesia programme directors, review of the
      Canadian Anaesthetists' Society records, and a Medline data-base search. Over the
      25 yr review period, 226 presentations have been given by 211 different
      participants, with the annual number of participants ranging from 6 to 13. The
      majority of participants have been male (85.3% vs 14.2% female, P < 0.001), and
      the majority of presentations have been clinical in nature (74% vs 26%
      laboratory, P < 0.01). Over half of all the presentations (53.1%) subsequently
      were published as scientific papers, and 71.7% of all participants practised
      anaesthesia in an academic environment at some point in their career. The
      Residents' Competition appears to have been successful in encouraging scientific
      excellence in physician's training in anaesthesia in Canada.

PMID- 8131227
TI  - Respiratory depression associated with patient-controlled analgesia: a review of
      eight cases.
AB  - Patient-controlled iv delivery of opioids for postoperative pain management is a
      popular alternative to the traditional im route of administration. However,
      occasional patients receiving opioids in this manner develop severe respiratory
      depression. The purpose of this paper is to determine the incidence of, and
      factors contributing to, the development of this complication. To do this, the
      Office of Medical Quality Improvement retrospectively searched for reports of
      respiratory depression in a database compiled from the charts of approximately
      1600 patients who had received PCA at the University of Alberta Hospitals in
      1992. Eight cases of serious respiratory depression were detected. Factors
      associated with the occurrence of respiratory depression included the concurrent
      use of a background infusion, advanced age, concomitant administration of
      sedative/hypnotic medications, and pre-existing sleep apnoea syndrome. No cases
      were attributed to operator error or equipment malfunction. In conclusion, the
      risk of respiratory depression with patient-controlled opioid administration is
      similar to that observed when opioids are delivered by the traditional im or
      spinal routes. The safe and effective use of patient-controlled analgesia depends
      upon knowledgeable medical and nursing staff, clearly defined nursing policy and
      procedures, and frequent patient follow-up.

PMID- 8131228
TI  - Bain circuit occluded by foreign body.
AB  - The purpose of this report is to describe a potentially hypoxic event which
      occurred during mask induction with the Bain circuit in a healthy. ASA I boy.
      Failure of induction occurred because a pop-off weight from a bubble bottle was
      lodged in the elbow connecting the Bain circuit to the mask and prevented gas
      flow. Pethick and Foex-Crampton Smith tests of the Bain circuit could also have
      missed this condition. Such an anaesthetic mishap could occur with any breathing
      circuit which is re-used. Although there was no serious misadventure, the
      potential for an hypoxic complication with either intra-venous induction of
      anaesthesia, or dislodging of the weight into the airway was significant. We
      conclude that the standard tests of system patency do not ensure safety.

PMID- 8131229
TI  - Unilateral mydriasis after induction of anaesthesia.
AB  - Unilateral mydriasis is a disturbing finding during anaesthesia and may indicate
      serious neurological injury. In addition, the assessment of abnormal neurological
      findings is limited during general anaesthesia, and therefore requires special
      consideration. I report finding a dilated right pupil (7 mm, nonreactive to
      light) after bronchoscopic tracheal intubation and induction of general
      anaesthesia in a frail, 74-yr-old woman with cervical subluxations and spinal
      cord impingement. The possible aetiology of the unilateral mydriasis includes the
      effects of anaesthetic agents, stellate ganglion block, impaired venous return
      from the head and neck, acute intracranial mass lesion or an haemorrhagic event,
      direct eye trauma, pre-existing medical or surgical conditions, and inadvertent
      direct deposition of alpha-adrenergic or anticholinergic agents in the eye.
      Consideration of these factors, the autonomic innervation of the eye, and an
      intraoperative "wake-up" test allowed satisfactory neurological assessment in
      this patient and surgery to proceed. Unilateral mydriasis, while unusual, may be
      seen during general anaesthesia and requires thorough knowledge of autonomic
      nerve pathways and pharmacology of the eye for correct diagnosis. In this case,
      mydriasis was considered to result from phenylephrine/lidocaine spray which was
      used to provide topical anaesthesia to the airway.

PMID- 8131230
TI  - Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold
      in rats.
AB  - The purpose of this study was to examine the anaesthetic requirement of
      intrathecal midazolam in a dose-response fashion in isoflurane-anaesthetized,
      tracheostomized rats, and to evaluate the apnoeic threshold after each
      intrathecal midazolam dose. Intrathecal midazolam, 5, 10, 20, and 30 micrograms,
      was administered to 25 anaesthetized tracheotomized rats. Isoflurane MAC was
      determined by the tail-clamp method. The effect of intrathecal midazolam on the
      apnoeic threshold was evaluated, and light and electron microscopy studies were
      performed on cervical, thoracic and lumbar sections of the spinal cord to
      investigate possible midazolam-induced neurotoxic effects. Intrathecal midazolam
      5, 10, 20 and 30 micrograms decreased isoflurane MAC by 16%, 31%, 42%, and 53%
      respectively (P < 0.05). The apnoeic threshold was increased by midazolam 5
      micrograms (from a PaCO2 of 4.25 +/- 0.55 to 5.28 +/- 0.76 kPa, P < 0.05) when
      compared with baseline values, but not further by additional doses. Light and
      electron microscopy studies on sections taken from the spinal cord of four
      animals did not show any morphological changes suggestive of midazolam-induced
      neurotoxicity when compared with similar preparations obtained from controls.
      These data suggest that intrathecal midazolam possesses dose-dependent
      antinociceptive properties which, associated with the ceiling effect of the
      apnoeic threshold obtained at the lowest midazolam dose and the lack of
      neurotoxic effects, may potentiate inhalational anaesthesia without producing
      marked respiratory depression.

PMID- 8131231
TI  - The microcirculation during enflurane and isoflurane anaesthesia in dogs.
AB  - The effects of enflurane and isoflurane of 0.75 and 1.5 MAC on capillary blood
      flow were studied by the microsphere (9 +/- 1 microns in diameter) method in two
      groups of seven dogs. Simultaneously, changes in the arteriolo-venular shunt were
      studied by collection of venous blood at a rate of 4.8 ml.min-1 for two minutes.
      Enflurane anaesthesia at 0.75 MAC decreased capillary blood flow in the thyroid
      glands (35% of control), left and right ventricular wall (59% and 50%), adrenal
      gland (59%), liver (63%), spleen (56%), pancreas (35%), omentum (20%), and small
      intestine (60%) and at 1.5 MAC it decreased further in the thyroid glands (15%),
      left and right ventricular wall (31% and 32%), adrenal gland (42%), liver (47%),
      spleen (31%), pancreas (23%), omentum (20%), stomach (45%), and small intestine
      (54%). No marked changes were noted in the brain, kidney, large intestine or
      skeletal muscle. The arteriolo-venular shunt was decreased in the kidney from an
      initial rate of 12.1 to 3.8% at 0.75 MAC and to 2.5% at 1.5 MAC enflurane. In
      contrast, during isoflurane anaesthesia, capillary blood flow remained unchanged,
      except for a decrease to the thyroid glands (43%) and right ventricular wall
      (74%) during 1.5 MAC anaesthesia. However, the arteriolo-venular shunt was
      increased in the brain from 12.0 to 29.7% and 33.0% during 0.75 and 1.5 MAC
      isoflurane anaesthesia, respectively. It also increased from 25.0 to 41.0% and
      46.3% in the skeletal muscle, and from 8.9 to 19.9% and 17.4% in the whole
      systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131232
TI  - John Albert Blezard (1888-1971).

PMID- 8131233
TI  - Anaesthetic management of a patient with a large neck mass.
AB  - Large thyroid masses present several potential difficulties for anaesthetists.
      These include distortion of the airway, endocrine disturbances, and metastatic
      effects. A typical case is presented and the anaesthetic management and
      considerations are described.

PMID- 8131234
TI  - Death from the oculocardiac reflex.

PMID- 8131235
TI  - Elevation of PetCO2 after submucosal epinephrine.

PMID- 8131236
TI  - Laryngoscope design.

PMID- 8131237
TI  - Spinal anaesthesia for caesarean section in a patient with brain neoplasma.

PMID- 8131238
TI  - Clonidine premedication for induced hypotension with total intravenous
      anaesthesia for middle ear microsurgery.

PMID- 8131239
TI  - Succinylcholine warning.

PMID- 8131240
TI  - Adverse events in anaesthesia: the wrong drug.

PMID- 8131241
TI  - Evoked potential monitoring during posterior fossa aneurysm surgery: a comparison
      of two modalities.
AB  - The purpose of this study was to compare and assess the ability of two different
      evoked potential (EP) modalities, median nerve somatosensory evoked potentials
      (SSEP) and brainstem auditory evoked potentials (BAEP) in monitoring for cerebral
      ischaemia and in predicting neurological outcome during posterior fossa aneurysm
      surgery. During 70 procedures, patients were monitored with both SSEP and BAEP.
      Temporary occlusion of an artery was used in 52 patients and permanent occlusion
      in 21 patients. A change was defined as a greater than 50% decrease in amplitude
      and/or an increase in latency greater than 1 msec of the N20 (cortical waveform)
      for SSEP monitoring and of the fifth peak for BAEP monitoring. Neurological
      assessment of the patient was performed immediately on emergence, after 24 hr and
      at the time of discharge. In total, 14 patients had an SSEP change which
      predicted a neurological deficit in eight patients (57%). Ten patients had a
      change in BAEP; six had a neurological deficit (60%). Five patients had a change
      in both, two had a deficit (40%). The incidence of false negative results (a
      neurological deficit but no EP change) for both modalities was 20% (SSEP 47%,
      BAEP 60%). The incidence of false positive results (an EP change but no deficit)
      was 13% overall (SSEP 11%, BAEP 7%). All patients who had a permanent EP change
      developed a neurological deficit. We did not find a difference in the ability of
      SSEP compared with BAEP in predicting neurological deficits but, using both
      modalities, the incidence of false negative results was decreased.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8131242
TI  - Preoperative naproxen sodium reduces postoperative pain following arthroscopic
      knee surgery.
AB  - This study was undertaken to assess the efficacy of a single preoperative dose of
      naproxen sodium in reducing postoperative pain and length of day surgery stay in
      patients undergoing arthroscopic knee surgery. A randomized, double-blind
      clinical trial was carried out on 66 ASA I and ASA II patients scheduled for
      arthroscopic knee surgery. The treatment group (n = 26) received two capsules
      containing 275 mg of naproxen sodium each, and the control group (n = 40)
      received placebo. Preoperative and postoperative visual analogue pain scores,
      postoperative analgesic requirements in hospital as well as 24 hr after
      discharge, and length of day surgery stay were studied. There was a decrease in
      postoperative pain, both in hospital (naproxen 0.7 +/- 1.2 vs placebo 2.2 +/-
      2.3) and at 24 hr after discharge (naproxen 0.8 +/- 1.9 vs placebo 3.8 +/- 3.2)
      (P = 0.0001). There was no difference in the need for in-hospital postoperative
      analgesics or in the time to discharge. However, there was a difference in the
      use of analgesics after discharge (naproxen group 30.4% vs placebo group 71.4%)
      (P < 0.01). The results of this study suggest that a single preoperative dose of
      550 mg naproxen sodium is effective in reducing postoperative pain in
      arthroscopic knee surgery, both in the immediate postoperative period and for up
      to 24 hr after the completion of surgery.

PMID- 8131243
TI  - Physical inactivity as a risk factor for coronary heart disease: a WHO and
      International Society and Federation of Cardiology position statement.
AB  - Coronary heart disease is responsible for a considerable amount of the morbidity
      and mortality from chronic diseases in industrialized countries. Many countries
      have therefore adopted prevention policies designed to reduce the prevalence of
      three of the major risk factors for coronary heart disease--high serum
      cholesterol, smoking, and high blood pressure. Physical inactivity is, however,
      also an important risk factor for developing coronary heart disease. This article
      presents a position statement by WHO and the International Society and Federation
      of Cardiology on physical inactivity and coronary heart disease.

PMID- 8131244
TI  - Male bias in health care utilization for under-fives in a rural community in
      western India.
AB  - A cross-sectional survey, in 1991, of 3100 families in 45 contiguous villages in
      the Pune district of Maharashtra state showed that 456 under-5-year-olds had
      suffered an acute respiratory infection and/or diarrhoea during the previous 7
      days. Significantly more boys (88.9%) than girls (76.5%) were treated by a
      registered private medical practitioner (odds ratio (OR) = 2.51). Referrals for
      further treatment were followed by parents significantly more often in the case
      of their sons (69.2%) than daughters (25%) (OR = 6.75). An average of Rs 35 (US$1
      1.16) was spent on the treatment of a son, compared with Rs 23 (US$ 0.76) for a
      daughter. In general, parents were willing to travel a greater distance (> 2 km)
      to seek medical treatment for their sons. These differences persisted even after
      adjusting for severity of illness, parent's income, occupation and education, and
      the birth order of the child. Intervention programmes directed at under-fives
      would need to correct the bias against girls if equitable access to health care
      is to be achieved.

PMID- 8131245
TI  - Nutritional status of preschool children in poor rural areas of China.
AB  - Described are the main findings of the first large-scale nutrition monitoring
      project carried out over a 4-year period in China. The nutritional status of
      nearly 10,000 preschool children in 18 comparatively poor rural areas in seven
      provinces was followed each year over the period 1986-89 in order to identify
      their major nutritional problems and improve their growth and development.
      Physical measurements were made and dietary surveys and biochemical tests were
      performed on a subsample of the children. The proportion of stunted and
      underweight children was far higher than the national average. Based on the
      possibilities offered by local circumstances, the prevalences of stunting and
      underweight were lowered and anaemia was greatly reduced. Along with the progress
      in nutrition monitoring, major efforts were made to train health workers, as well
      as to encourage increased production of green vegetables, poultry, and small
      livestock. The wealth of information collected and the experience gained may
      serve as a baseline record, the project currently being expanded to cover 100
      counties throughout China.

PMID- 8131246
TI  - Clinical signs of pneumonia in children attending a hospital outpatient
      department in Lesotho.
AB  - To determine the value of clinical findings for the diagnosis of pneumonia, we
      evaluated 950 children who presented with respiratory illness to the outpatient
      department of the Queen Elizabeth II Hospital, Maseru, Lesotho. Those children at
      high risk for pneumonia and a systematically selected 20% sample of children at
      low risk were examined in turn by a nurse, a general practitioner, and a
      paediatrician; a chest radiograph was recorded for each child. Pneumonia was
      defined as radiographic findings compatible with the disease as interpreted by a
      paediatric radiologist. A respiratory rate > or = 50 breaths/minute was a
      sensitive sign for pneumonia among infants (sensitivity range for the three
      examiners: 59-79%), but identified a progressively smaller proportion of children
      with pneumonia in older age groups. Adjusting the respiratory rate for age using
      a threshold of > or = 40 breaths/minute for children aged > or = 12 months
      improved the sensitivity, but identified < 30% of children with pneumonia aged >
      or = 24 months. No drop in sensitivity with age was found when respiratory rate
      thresholds were evaluated for children with more severe radiographic evidence of
      pneumonia.

PMID- 8131247
TI  - Intra-household correlations in maternal-child nutritional status in rural
      Guinea: implications for programme-screening strategies.
AB  - It is commonly assumed in public health practice that households in developing
      country settings are relatively homogeneous with respect to nutritional status.
      To the extent that this assumption is valid, nutritional assessments of mothers
      or individual children would provide an effective screening mechanism for
      household-level maternal-child nutritional risk. However, there has been no
      confirmation of the strength of intra-household correlations in nutritional
      status among women and children. Using data from a cross-sectional survey
      undertaken in 1990 in rural central Guinea, the present study investigates the
      nature of within-household relationships in maternal and child nutritional status
      and considers the implications for programme screening strategies. Mothers and
      their surviving children under 5 years of age are the focus of the analysis.
      Correlations between maternal and child nutritional levels are assessed and the
      performance of maternal-child nutritional indicators as screening tools for
      household nutritional risk are formally evaluated by analysing the sensitivity,
      specificity, and positive-negative predictive values of various indicators.

PMID- 8131248
TI  - Strategies for laboratory HIV testing: an examination of alternative approaches
      not requiring Western blot.
AB  - Advances in laboratory tests for antibodies to human immunodeficiency virus (HIV)
      have permitted the development of alternative HIV testing strategies that do not
      require use of the Western blot approach. Three strategies are proposed. In
      strategy I, sera are tested for HIV antibody using an enzyme-linked immunosorbent
      assay (ELISA)/rapid/simple (ERS) test; in strategy II, sera reactive in an
      initial ERS test are retested using a second ERS test; strategy III involves
      retesting with a third ERS test all sera reactive in two previous ERS tests.
      Where the objective is identification of asymptomatic HIV-infected individuals,
      strategy III is proposed where HIV prevalences in the study population are < or =
      10%, and strategy II at prevalences > 10%. Strategy II is recommended where the
      diagnosis of HIV-related disease requires HIV testing. For serosurveillance,
      strategy II is recommended if the prevalence is < or = 10%, and strategy I if the
      prevalences are > 10%. Use of strategy I is recommended for transfusion and
      transplantation safety, at any prevalence. Lower-cost laboratory HIV testing will
      permit such testing to become more widely available.

PMID- 8131249
TI  - Anthrax control and research, with special reference to national programme
      development in Africa: memorandum from a WHO meeting.
AB  - The prevalence of anthrax in both animal and human populations has been
      increasing in Africa. It was therefore appropriate for this WHO meeting to be
      convened in an endemic area of the Western Province of Zambia in 1992. The
      participants reviewed anthrax epidemiology and control in some African countries,
      elaborated national anthrax control and research programmes in Africa, discussed
      international cooperation and work plans, and elaborated recommendations for
      anthrax control in Africa. The discussions centred on anthrax surveillance and
      reporting systems, diagnosis, vaccine production and immunization, disinfection
      and decontamination, carcass disposal, treatment of human cases, health systems,
      as well as intersectorial cooperation between public health services, veterinary
      services and other services such as wildlife conservation, so that national
      control programmes could take full account of the conditions prevailing in
      epidemic situations in Africa. The recommendations are applicable in other
      regions where anthrax poses similar problems in public, animal and environmental
      health.

PMID- 8131250
TI  - Serological diagnosis of HIV infection using oral fluid samples.
AB  - The serological identification of antibodies to human immunodeficiency virus
      (HIV) in blood is the most widely used method to diagnose HIV infection.
      Recently, however, the use of oral fluid samples for the detection of antibodies
      to HIV has been suggested as an alternative. This review describes some basic
      information about oral fluids, the application of these samples for HIV testing,
      and summarizes results from many of the studies performed using HIV tests with
      oral fluids. The fluids obtained from the oral cavity include saliva and
      crevicular fluid, and can be collected directly (by dribbling) or by using
      commercially available devices. The immunoglobulin content of oral fluids is
      similar to that of blood, but their levels are less. However, the use of an HIV
      IgG antibody capture assay (GAC ELISA) designed specifically for testing oral
      fluids, and certain routine HIV blood tests that have been optimized for use with
      oral fluids, has produced encouraging results. A number of studies, including
      several in developing countries, report that the sensitivities and specificities
      of these optimized tests lie in the range 95-100% and 98-100%, respectively.
      Also, the performance of the GAC ELISA was consistent and in general, excellent.
      The article identifies several issues that need to be addressed before a
      recommendation on the routine use of oral fluid samples for HIV antibody
      detection can be made.

PMID- 8131251
TI  - Hereditary disorders in the Eastern Mediterranean Region.
AB  - Hereditary diseases and congenital malformations have been reported to affect 2
      5% of all live births. Available evidence suggests that genetic disorders are
      equally important also in countries of the Eastern Mediterranean Region.
      Considerable achievements have been made over the last two decades in controlling
      communicable diseases in the region. Concurrently, there has been a mounting
      awareness of the increasing importance of hereditary disorders. Certain
      genetically determined diseases such as the haemoglobinopathies and enzymopathies
      are extremely common in the region and the need to initiate public health
      measures for their control is increasingly being recognized. The following
      factors may contribute to the elevated prevalence of genetically determined
      disorders: the high consanguinity rates; the high frequency of
      haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency; the trend
      of continuing to bear children up to menopause; the general lack of public
      awareness about genetic diseases; and the dearth of genetic services in the
      region. These and some other related issues are discussed in detail in this
      review article.

PMID- 8131252
TI  - A salmonella data bank for routine surveillance and research.
AB  - A salmonella data bank has been established in the State of Brandenburg, Germany,
      with due steps being taken to ensure the protection of personal data. The system
      of data collection and rapid return of information to the local health and
      veterinary services have become essential elements in intersectoral cooperation
      in case investigation, disease prevention, and epidemiological research. A number
      of issues, particularly those concerning the pathways of infection,
      characteristics of clusters of cases, and the infection of different population
      strata can now be examined and monitored. An important feature of the data bank
      is its accessibility by local as well as central state services using a PC-based
      program and the wide interdisciplinary circulation of regular reports.
      Preliminary results on the data volume, age distribution of cases, and salmonella
      isolation rates in different population strata are presented. The data bank
      supports studies on marketing and purchasing patterns of agricultural products
      representing potential vehicles of infection, and it should encourage
      investigations to trace the reservoirs of infection and contamination points
      along the food chain.

PMID- 8131253
TI  - Falciparum malaria in eastern Thailand: a randomized trial of the efficacy of a
      single dose of mefloquine.
AB  - Reported are the results of a randomized trial of a single dose of mefloquine (15
      mg/kg or 25 mg/kg body weight) for the treatment of uncomplicated multidrug
      resistant falciparum malaria. Of the 110 adult patients enrolled in the study 57
      were randomly assigned to the 15 mg/kg group and 53 to the 25 mg/kg group. The
      baseline characteristics of the patients did not differ significantly in the two
      groups, except that those in the 15 mg/kg group had lower haemoglobin levels.
      Adverse effects following treatment were commoner in the 25 mg/kg group, but not
      significantly so. Seven patients (6%) did not complete the 42-day follow-up. The
      parasitological failure rates in the 15 and 25 mg/kg groups were, respectively,
      50% (28/56) and 43% (25/53) on day 28, and 62% (33/53) and 56% (28/50) on day 42.
      Treatment failures were not correlated with the serum mefloquine concentrations
      on day 2, and 13 out of 19 patients with serum mefloquine concentrations > 2000
      micrograms/l on day 2 showed an R response during the follow-up. The mean ratio
      between the concentrations of the (SR)-(-) and (RS)-(+) enantiomers of mefloquine
      on day 2 was 3.37, indicating that there are differences in their
      pharmacokinetics. Re-treatment of patients who showed an R response with seven
      days of quinine (30 mg.kg-1.day-1)+tetracycline (25 mg.kg-1.day-1) was successful
      in 93% of the cases.

PMID- 8131254
TI  - Impact of DDT indoor residual spraying on Phlebotomus argentipes in a kala-azar
      endemic village in eastern Uttar Pradesh.
AB  - Data on the operational efficacy of DDT indoor residual spraying against
      Phlebotomus argentipes, the vector of kala-azar in India, are scarce. We
      therefore undertook a study of the impact on kala-azar and its vector of DDT
      indoor residual spraying in the Varanasi district of eastern Uttar Pradesh.
      Preliminary results indicate that after two rounds of DDT spraying in one village
      no P. argentipes were found during the peak vector season; in contrast, a large
      number of these sandfies were collected in the unsprayed comparison village.

PMID- 8131255
TI  - Pharmacokinetics of mefloquine alone or in combination with artesunate.
AB  - A randomized comparative trial of the pharmacokinetics and pharmacodynamics of
      oral doses of mefloquine and of mefloquine in combination with artesunate was
      carried out on 20 Thai male patients with acute, uncomplicated falciparum
      malaria. The patients were randomized to receive either mefloquine alone (8
      patients; 1250 mg of mefloquine--initial dose, 750 mg; followed 6 hours later by
      500 mg), or in combination with oral artesunate (12 patients--initial dose, 200
      mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12
      hours later, respectively). The patients who received mefloquine alone all showed
      initially good responses to the treatment, with mean +/- SD values for the fever
      clearance time (FCT) and parasite clearance time (PCT) of 44.7 +/- 43.1 hours and
      82.3 +/- 52.3 hours, respectively. Two patients had recrudescences on day 20 and
      day 31 (RI response). The cure rate was 75%, and one patient had Plasmodium vivax
      in his peripheral blood on day 52. The patients who received the combination
      treatment were clinically markedly improved, with a relatively shorter FCT (31.2
      +/- 12.4 hours) and significantly shorter PCT (47.5 +/- 19.6 hours). Four had
      recrudescences on days 12, 18, 26 and 33; the cure rate was 66%. Artesunate
      caused three significant changes in mefloquine pharmacokinetics: a decrease in
      the maximum concentration (Cmax: 1623 ng.ml-1 versus 2212 ng.ml-1); an increase
      in the clearance rate (Cl/f:2.9 ml.min-1.kg-1 versus 1.1 ml.min-1.kg-1); and an
      expansion of the volume of distribution (Vdz/f: 31.8 l.kg-1 versus 25.0 l.kg-1).

PMID- 8131256
TI  - A review of randomized controlled trials of routine antimalarial drug prophylaxis
      during pregnancy in endemic malarious areas.
AB  - Current global recommendations for routine malaria chemoprophylaxis in pregnant
      women living in endemic malarious areas are not clear. To assist in policy
      formulation, the evidence from randomized controlled trials was reviewed. The
      literature was extensively searched, and studies identified were systematically
      analysed in relation to outcomes in the mother and the baby. Routine
      chemoprophylaxis appears to have an effect on antenatal morbid episodes and
      packed cell volume. There is a trend towards higher birth-weight values in
      chemoprophylaxis groups, which reached statistical significance in some studies.
      Evidence of an effect on gestation was only examined in one study. The effects on
      perinatal and neonatal mortality have only been examined in a few studies, with
      small sample sizes. The analysis questions whether routine malaria
      chemoprophylaxis is the best use of scarce resources in developing countries, and
      suggests that chemoprophylaxis might be targeted at anaemic women and
      primigravidae. Large controlled trials, with treatment available to placebo
      groups, are required to test whether routine chemoprophylaxis has advantages over
      early, effective treatment of clinical malaria.

PMID- 8131257
TI  - The development of parvalbumin and calbindin-D28k immunoreactive interneurons in
      kitten visual cortical areas.
AB  - Calbindin-D and parvalbumin are calcium binding proteins which are found in non
      overlapping subpopulations of GABA-ergic interneurons in mammalian neocortex. We
      studied the development of these calcium-binding proteins in interneurons of cat
      striate and extrastriate cortical areas which have differing patterns of
      connectivity and follow different developmental timetables. We examined primary
      visual areas 17 and 18, secondary visual area 19, medial lateral suprasylvian and
      lateral suprasylvian areas (MLS and LLS) and association areas 7 and the splenial
      visual area from the day of birth (P0) through P101. Parvalbumin-immunoreactive
      (ir) interneurons followed the inside-out pattern of maturation of cortical
      laminae. They were located only in infragranular layers at the earliest ages and
      were not observed in the overlying cortical plate. At 3 weeks of age, when
      cortical lamination is mature, parvalbumin stained cells were found in all
      cortical layers except layer I. The number of stained secondary and tertiary
      dendrites in the parvalbumin-ir interneuronal population decreased with age. This
      change was associated with a shift in the molecular weight of parvalbumin
      detected on Western blots. During the first postnatal week, the area 17/18 border
      contained more parvalbumin-ir neurons than other visual areas. The developmental
      pattern of calbindin staining differed considerably from the parvalbumin staining
      pattern. Very few calbindin-ir interneurons were seen in area 17 during the first
      2 weeks of life. In lateral cortical areas, calbindin-ir neurons were located in
      cortical plate, infragranular layers of cortex and white matter/subplate.
      Calbindin-ir neurons increased in supragranular layers of secondary cortical
      areas by P7 and in area 17 by P20. In the mature cortex, the calbindin staining
      pattern was bilaminar, with a dense band of calbindin-ir cells in layer II and a
      second band in layers V-VI. There was no difference in the distribution of
      calbindin-ir neurons among visual areas at maturity.

PMID- 8131258
TI  - Localization of c-fos, c-jun, and hsp70 mRNA expression in brain after neonatal
      hypoxia-ischemia.
AB  - The sites of expression of early response mRNAs were determined in the brains of
      7-day-old rat pups exposed to unilateral carotid artery ligation followed by 3 h
      of hypoxia. Pups were sacrificed after recovery periods ranging from 10 min to 24
      h. In agreement with our previous northern blot analysis, in situ hybridization
      of coronal brain sections to probes for c-fos, c-jun, and heat-inducible hsp70
      revealed a marked induction and subsequent disappearance of all three mRNAs
      during this time period. We observed co-localization of the 2 immediate early
      gene (IEG) mRNAs, c-fos and c-jun, which encode proteins that act in combination
      to regulate subsequent gene expression. These mRNAs were expressed in all regions
      known to be vulnerable to permanent injury in this model, such as the cortex,
      hippocampus, and striatum, as well as in other regions that are spared from
      permanent damage, such as contralateral cortex and lateral ventricular
      neuroepithelium. The temporal and regional co-localization of c-fos and c-jun
      suggests that the transcriptional regulatory activity of their protein products
      could play a role in plasticity associated with death or recovery from injury in
      the immature brain. Hsp70 mRNA expression was induced in nearly all of the
      animals that were positive for IEG mRNAs. Although the most frequent site of
      expression for all three mRNAs was the ipsilateral cerebral cortex, hsp70
      expression was restricted to the ipsilateral hemisphere and absent from a number
      of structures that were positive for c-fos and c-jun. In addition, the patterns
      of expression of hsp70 within specific structures frequently differed from those
      of the IEGs, implying that although both cellular early response systems are
      activated in this model, their specific functions are carried out within
      different microenvironments.

PMID- 8131259
TI  - Exogenous cholecystokinin activates cFos expression in medullary but not
      hypothalamic neurons in neonatal rats.
AB  - The central distribution of neurons activated to express cFos immunoreactivity in
      response to peripheral administration of cholecystokinin octapeptide (CCK) was
      examined in 2-day-old rats. Similar to previous results in adult rats, neurons in
      specific subregions of the area postrema and nucleus of the solitary tract (NST)
      expressed cFos after CCK treatment. However, in marked contrast to results in
      adult rats, CCK treatment in neonates did not stimulate cFos expression in
      hypothalamic neurons or in other forebrain areas, and did not increase plasma
      oxytocin levels. These results suggest that vagal sensory activation of intrinsic
      brainstem circuits may be sufficient for the known inhibitory effects of
      exogenous CCK on gastric motility and feeding in neonatal rats. The prominent
      forebrain activation produced by CCK administration in adult rats likely reflects
      later maturation of direct and relayed ascending neural projections from the NST.

PMID- 8131260
TI  - Changes in extracellular calcium concentration in the immature rat cerebral
      cortex during anoxia are not influenced by MK-801.
AB  - The extracellular calcium concentration ([Ca2+]ec) was recorded by calcium
      sensitive microelectrodes in the parietal cortex of 9-11 day old rats during
      anoxia. During the first 10 min of anoxia, [Ca2+]ec increased from 1.1 mM to 1.5
      +/- 0.23 mM, and thereafter it started to decrease reaching below basal level
      after around 13 min. The [Ca2+]ec decrease was either slow and continuous, or
      biphased with a rapid initial decrease followed by a continuous slow decrease.
      After 60 min of anoxia, the [Ca2+]ec had reached 0.2-0.3 mM. Changes in [Ca2+]ec
      in animals treated with the NMDA receptor antagonist MK-801 (0.3 mg/kg i.p.) did
      not display any significant differences compared to controls. Thus, the strong
      neuroprotective effect of MK-801 in ischemic situations in the immature brain can
      not be explained by a prevention of calcium entry during anoxic depolarization.

PMID- 8131261
TI  - Disruption of neuronal migration in the neocortex of the dreher mutant mouse.
AB  - To analyze developmental abnormalities related to neuronal migration in the
      dreher mutant mouse, the neocortical cytoarchitecture of dreher and control mice
      were examined in Nissl-stained serial sections by light microscopy. In general,
      the dreher neocortex has six layers which are similar in size and thickness to
      those observed in normal mouse neocortex. However, in dreher neocortex, three
      types of abnormalities were found: (1) an increase in the number of diffusely
      distributed neurons in layer I, (2) small, ectopic collections of neurons in
      layer I, and (3) isolated disturbances of local cytoarchitecture characterized by
      neuron-free space distributed in areas between layer II to IV. The occurrence of
      small, punctate deficits in the dreher neocortex may be secondary to disruptions
      of the radial glial fiber system and neuronal migration. The fact that
      cytoarchitectonic abnormalities of several types were found in the dreher
      neocortex may be useful in analyzing the relationship between radial glial fibers
      and migrating young neurons, the synaptic connections which are formed by
      ectopically situated neurons, and the mechanism of formation of sporadically
      distributed neocortical abnormalities.

PMID- 8131262
TI  - Coordinate regulation of tubulin and microtubule associated protein genes during
      development of hamster brain.
AB  - The present study documents the patterns of mRNA expression for 5 different
      tubulin genes and 4 of the structural microtubule-associated protein (MAP) genes
      during normal development of hamster forebrain. Northern blotting in conjunction
      with densitometric analysis was used to study changes in the levels of the mRNAs
      for alpha 1-tubulin, classes beta I-, beta II-, beta III- and beta IV-tubulin, as
      well as the mRNAs for tau, MAP1A, MAP1B and MAP2, using total RNA isolated from
      hamster forebrain at various embryonic (E) and postnatal (P) stages.
      Densitometric analyses of the autoradiograms from the Northern blots revealed
      that each of the tubulin genes exhibited distinct developmental patterns of
      expression, several of which appeared to be temporally correlated with the
      expression of specific MAP mRNAs. The beta I-, beta II- and beta III-tubulin
      mRNAs increased rapidly between late embryonic stages to birth, reached peak
      levels early in the first postnatal week, and declined thereafter. alpha 1
      Tubulin mRNA was easily detected during embryonic stages, rose to peak levels at
      P7-P9 and then gradually declined. A similar pattern was seen for tau mRNA. After
      the first postnatal week, the size of the tau mRNA also shifted to a slightly
      larger size, presumably due to differential splicing. beta IV-Tubulin mRNA levels
      did not become significant until very late in postnatal development (3-4 weeks).
      MAP2 mRNA expression was unusual in that peak levels were reached at two
      different stages of development--an initial peak occurred in the first postnatal
      week, followed by a decline, and then a second rise occurred during the third and
      fourth postnatal weeks. The expression of the beta IV-tubulin mRNA coincided
      temporally with the second peak in MAP2 mRNA expression. MAP1B mRNA abruptly
      reached high levels at birth, remained abundant during the first two postnatal
      weeks, and then decreased. In contrast, MAP1A mRNA levels were low in the initial
      postnatal interval and increased only at very late developmental stages. The
      findings of a temporal correspondence in expression of high levels of tau and
      MAP1B with beta I-, beta II-, beta III- and alpha 1-tubulin mRNAs suggest that
      this profile of gene expression is one that endows greater plasticity to the
      neuronal cytoskeleton. Conversely, the transition to increased expression of beta
      IV-tubulin, MAP1A, and a larger tau mRNA species defines a portion of the
      molecular pattern that underpins the increased stability of neuronal form during
      maturation.

PMID- 8131263
TI  - Development of laminar expression of the m2 muscarinic cholinergic receptor gene
      in rat visual cortex and the effect of monocular visual deprivation.
AB  - The postnatal development of laminar pattern of the m2 muscarinic acetylcholine
      receptor subtype mRNA in the visual cortex of both normally raised and
      monocularly deprived rats (one eyelid sutured at the age of 11 days) was studied
      using in situ hybridization histochemistry and computer-assisted image analysis.
      In normally raised rats, on birth, the m2 transcript was found to be more
      concentrated in the superficial zones of the cortex. This laminar pattern alters
      to a more homogeneous distribution of the label throughout the cortex already
      detectable on day 7. From day 10 onwards a bimodal laminar pattern gradually
      develops with increased mRNA levels in layer IV and upper layer VI. From
      postnatal day 21 onwards the hybridization peak in layer VI decreases as compared
      to the peak level in layer IV resulting in an adult distribution with highest
      labeling in layer IV, low labeling in layer I to III and moderate labeling in
      layers V and VI. Monocular deprivation results in decreased m2 mRNA levels in
      visual cortical layers IV-VI in both deprived and non-deprived cortices already
      detectable at the age of 18 days and persisting up to the age of 21 days; but
      this effect disappears following further deprivation until adulthood. The data
      suggest that the changes in m2 receptor level from a more homogeneous
      distribution to a bimodal pattern during postnatal development seem to be related
      to synaptogenesis and final tuning of connectional pattern within the rat visual
      cortex.

PMID- 8131264
TI  - Analysis of the anatomical distribution of GAD67 mRNA encoding truncated glutamic
      acid decarboxylase proteins in the embryonic rat brain.
AB  - During development of the central nervous system (CNS) the gene that encodes the
      67 kDa form of glutamic acid decarboxylase (GAD) undergoes alternative splicing.
      The alternatively spliced variants include an exon (referred to as ES, for
      embryonic stop) that contains a premature stop codon. The detection of mRNA
      containing the ES exon in embryonic rat brain has been previously reported (Proc.
      Natl. Acad. Sci., 87 (1990) 8771-8775). We have used in situ hybridization to
      identify the anatomical distribution of ES mRNA in the embryonic rat brain during
      two stages of development, embryonic day 17 (E17) and E20. At E17, GAD67 mRNA was
      expressed in several CNS regions that were destined to contain GABAergic neurons
      when mature. ES transcripts were predominantly localized to ventricular zones and
      other regions associated with populations of proliferative cells at E17 and E20.
      At both ages, however, the alternatively spliced variants were also detected in
      regions of brain associated with migratory or post-mitotic neurons. GAD67
      transcripts that did not include the ES exon were localized to anatomical areas
      that contained post-mitotic, and often post-migratory neurons. The temporal and
      spatial disappearance of mRNA containing the ES exon generally followed a caudal
      to-rostral gradient which paralleled neuronal terminal mitosis and
      differentiation.

PMID- 8131265
TI  - Reciprocal expression of cell-cell coupling and voltage-dependent Na current
      during embryogenesis of rat telencephalon.
AB  - Using whole-cell patch-clamp techniques in situ (whole-tissue and tissue slices),
      we have studied two aspects of rat telencephalic cell development during the
      period of embryogenesis starting at E12. The first aspect was related to
      junctional coupling as revealed by low input resistance, intercellular dye spread
      and pharmacologic blockade. Coupling appeared to decrease with time, both in
      extent and occurrence. The second aspect dealt with cell excitability as revealed
      by voltage-dependent Na current (INa) expression. Immature action potentials and
      their underlying INaS were present in a small proportion of E12 cells. These
      currents were blocked 36% and 78% by 10(-7) M and 10(-6) M tetrodotoxin (TTX),
      respectively. From then onward, INaS got larger and more prevalent while no
      obvious changes in kinetics were observed. At E21, INaS were abolished by 10(-7)
      M TTX and channel density apparently was sufficient to support overshooting yet
      still immature action potentials.

PMID- 8131266
TI  - Proficiency testing, matrix effects, and method evaluation.

PMID- 8131267
TI  - Commercial assays for serum osteocalcin give clinically discordant results.
AB  - Serum samples from 9 healthy controls and from subjects with primary
      hyperparathyroidism (n = 5), Paget disease (n = 3), pregnancy (n = 5),
      glucocorticoid therapy (n = 5), postmenopausal osteoporosis (n = 10), and renal
      failure (n = 10) were used to assess the clinical agreement among eight
      commercially available assay kits for osteocalcin (OC). These kits differ in
      their assay configurations (six radioimmunoassays, two immunoradiometric assays),
      standards (five bovine, three human), and antibodies (six polyclonal, two
      monoclonal). Individual results were divided by the mean OC of the control
      subjects for each assay and expressed as percentage deviations. The expected wide
      variation in absolute OC concentrations between kits was only partially reduced
      by this transformation. Agreement was equally poor when absolute OC
      concentrations were compared with the reference ranges quoted by the
      manufacturers. The discordance was particularly marked in renal failure,
      presumably because of immunoreactive fragments, and in osteoporosis. Systematic
      differences could not be attributed to assay format, species source of standard,
      or antibody specificity. We conclude that results cannot be compared between
      assays even when normalized against healthy subjects, and that standardization is
      needed.

PMID- 8131268
TI  - Two methods for measuring carbohydrate-deficient transferrin in inpatient
      alcoholics and healthy controls compared.
AB  - Carbohydrate-deficient transferrins (CDTs), naturally occurring glycosylated
      transferrin proteins, are reported to be increased in the serum of individuals
      who consume large quantities of alcohol (ethanol). We compared two methods for
      the separation and quantification of CDT, using the same alcohol-dependent
      patients and age-, gender-, and race-matched controls as sources of samples for
      both assays. There was good correlation (r = 0.89) between the microcolumn anion
      exchange chromatography/RIA (MAEC/RIA) procedure and the isoelectric focusing,
      immunoblotting, and laser densitometry (IEF/IB/LD) procedure. Receiver operating
      characteristic analysis suggested that the IEF/IB/LD procedure would perform
      slightly better than MAEC/RIA for the overall population. However, both assays
      were much more sensitive for the detection of heavy alcohol consumption in men,
      compared with women. Alcohol consumption in the week prior to CDT measurement
      correlated only weakly with the concentrations measured with either assay.

PMID- 8131269
TI  - Hematofluorometric determination of erythrocyte zinc protoporphyrin: oxygenation
      and derivatization of hemoglobin compared.
AB  - We compared oxygenation and derivatization of hemoglobin for the
      hematofluorometric determination of erythrocyte zinc protoporphyrin (ZPP). No
      statistically significant differences were found when the volume ratio of sample
      to ProtoFluor reagent (which converts hemoglobin to cyanohemoglobin) was changed
      from 1:1 to 1:4. With the derivatizing reagent, results were significantly higher
      than those obtained after thorough aeration of the blood sample (P < 0.001). The
      differences between the results obtained by the two procedures were greater for
      ZPP values in the reference range. Although the correlation between methods was
      high (r = 0.997), interconversion of the results by means of the regression
      equation was not acceptable because the standard error of the estimate from the
      regression (Syix = 0.36 micrograms/g hemoglobin) was greater than the error
      acceptable medically (criterion of Harris: Arch Pathol Lab Med 1988; 112:416-20).

PMID- 8131270
TI  - Detecting benzodiazepines: immunoassays compared with negative chemical
      ionization gas chromatography/mass spectrometry.
AB  - We tested 231 urine samples by six immunoassay methods--EMIT d.a.u., EMIT II,
      Roche Abuscreen Online, Abbott TDx, Diagnostic Products Corp. (DPC) double
      antibody radioimmunoassay (RIA), and Biosite Triage--and by negative chemical
      ionization gas chromatography/mass spectrometry to determine how the immunoassays
      performed on samples selected for suspected benzodiazepine use (n = 100) and in
      random urine drug screening (n = 131). In general, all of the assays were
      successful in detecting oxazepam and related metabolites, even at concentrations
      below the stated cutoffs. However, the negative predictive value of
      benzodiazepine immunoassays for samples selected for suspected benzodiazepine use
      ranged from 86% to 96%. A primary difference between the test kits was the
      ability of DPC RIA and Triage to detect lorazepam when other assays did not.
      Contrary to previous reports, pretreatment of specimens with glucuronidase was
      not necessary to detect oxazepam-related metabolites with these immunoassays.

PMID- 8131271
TI  - Localized in situ amplification (LISA): a novel approach to in situ PCR.
AB  - Amplification of specific gene target sequences has become a routine molecular
      procedure in a variety of laboratories. When coupled with either a direct or
      indirect method of detecting amplified product, in situ amplification offers an
      extremely powerful investigative tool. We describe a protocol for a localized in
      situ amplification (LISA) reaction that includes tissue-culture cloning rings and
      allows for the amplification of gene target sequences in specific regions of
      paraffin-embedded tissue sections. Digoxigenin-11-dUTP was added to the
      amplification reaction and thus incorporated into the amplified products,
      providing a mechanism by which direct nonisotopic detection could be performed.
      To demonstrate the approach, LISA was performed on known positive Pneumocystis
      carinii rat lung tissues, with primers specific for the P. carinii rRNA gene
      sequence.

PMID- 8131272
TI  - Enzymatic diagnosis of aspartylglycosaminuria by fluorometric assay of
      glycosylasparaginase in serum, plasma, or lymphocytes.
AB  - Serum, plasma, and lymphocytes from aspartylglycosaminuria (AGU) patients and
      carriers and from normal controls were incubated with a fluorescent
      glycosylasparaginase substrate, L-aspartic acid beta-(7-amido-4-methylcoumarin),
      and the release of 7-amino-4-methylcoumarin was measured fluorometrically after
      incubation for 1-4 h. The mean glycosylasparaginase (EC 3.5.1.26) activity in
      normal serum, plasma, and lymphocytes was 20.2 (SD 5.0) mU/L (n = 24), 17.5 (SD
      5.0) mU/L (n = 24), and 242 (SD 108) mU/g protein (n = 17), respectively. The
      corresponding values in the Finnish AGU patients were 0.7 (SD 0.4) mU/L (n = 10),
      0.3 (SD 0.3) mU/L (n = 10), and 6.0 (SD 4.6) mU/g protein (n = 7). No overlapping
      values were obtained between the AGU patients and the carriers in any of the
      samples, but the values between the carriers and controls were overlapping in 28
      of 29 serum, 22 of 29 plasma, and 4 of 21 lymphocyte samples. Thus, the
      fluorometric glycosylasparaginase assay in various blood samples allows specific
      detection of the enzyme defect in AGU, but cannot be used for reliable detection
      of carriers of the disease.

PMID- 8131273
TI  - Nonlinearity of high-density lipoprotein cholesterol determinations is matrix
      dependent.
AB  - The majority of methods for determining high-density lipoprotein (HDL)
      cholesterol failed the 1991 College of American Pathologists (CAP) linearity
      survey (sets LN2-A, B, C). We hypothesized that they failed because of the survey
      material matrix. We evaluated linearity with dextran sulfate or phosphotungstate
      as the precipitating reagents for several methods: Ektachem; TDx; Sigma;
      Dimension; Cobas Fara, with Roche reagents; and the Hitachi 736, with
      precipitating reagents from Boehringer Mannheim Diagnostics. We tested CAP survey
      material, Sigma HDL-cholesterol control material, and a fresh serum pool for
      linearity, using the polynomial method. All of the methods were nonlinear for the
      CAP material and for the controls precipitated after dilution. Five of eight
      methods were linear for the control materials precipitated before dilution. All
      methods but one were linear for the serum pool. These results demonstrate that
      the source of the nonlinearity is located in the precipitation step and depends
      on the sample matrix.

PMID- 8131274
TI  - Screening for familial defective apolipoprotein B-100 with improved U937 monocyte
      proliferation assay.
AB  - Frostegard et al. (J Lipid Res 1990;31:37-44) demonstrated that the proliferation
      of the human monocyte cell line U937 is critically dependent on the uptake of low
      density lipoprotein (LDL) via the apo B, E (LDL) receptor, a characteristic that
      was used to detect patients with familial defective apolipoprotein B-100 (FDB).
      Here we applied this principle to develop a simple and reproducible assay for the
      detection of patients with functionally defective LDL. We added serum to U937
      cells in cholesterol-free incubation medium and determined the increase in cell
      number after a 72-h incubation at 37 degrees C by using an electronic cell
      counter. Sera from 10 normolipidemic individuals and from 34 patients with type
      IIa hyperlipoproteinemia stimulated the growth of U937 cells in proportion to the
      exogenous cholesterol concentration (r = 0.83, P < 0.001) and the LDL-cholesterol
      concentration (r = 0.81, P < 0.001). However, sera from 16 patients with FDB
      stimulated less cell proliferation than did sera from patients with type IIa
      hyperlipoproteinemia with equal LDL-cholesterol concentrations. With a 15%
      reduction in growth as the cutoff value, this test had a sensitivity and
      specificity for diagnosis of FDB of 87.5% and 100%, respectively. The improved
      U937 monocyte proliferation assay can be used for screening hypercholesterolemic
      patients to detect individuals with functionally defective LDL.

PMID- 8131275
TI  - Quantification of lipoprotein(a) in plasma by assaying cholesterol in lectin
      bound plasma fraction.
AB  - Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle in which
      apolipoprotein(a) [apo(a)] is disulfide-linked to apolipoprotein B (apoB). High
      concentrations of Lp(a) in plasma are associated with an increased risk of
      coronary heart disease (CHD). Lp(a) has traditionally been measured by
      immunoassay and expressed as total mass of Lp(a). Measuring Lp(a) by its
      cholesterol content will provide a way to directly compare Lp(a) with other
      lipoproteins that are measured by cholesterol. We have developed an assay to
      quantify Lp(a) by its cholesterol content [Lp(a)-C], using lectin affinity to
      isolate Lp(a) from other lipoproteins, and then measuring the cholesterol within
      the isolated fraction. We compared the Lp(a)-C assay with an ELISA for Lp(a) mass
      in 47 plasma samples from normotriglyceridemic, fasting individuals with high
      Lp(a) contents (mean +/- SD, 446 +/- 350 mg/L). The mean Lp(a)-C concentration
      was 110 +/- 89 mg/L and correlated very highly with Lp(a) mass (r = 0.9975).
      Lp(a)-C measurement is an alternative method to screen for this CHD risk factor.

PMID- 8131276
TI  - Limitations of the Friedewald formula for estimating low-density lipoprotein
      cholesterol in alcoholics with liver disease.
AB  - The accuracy of the Friedewald formula in estimating low-density lipoprotein
      (LDL) cholesterol was investigated in 47 alcoholic patients with liver disease
      (21 minimal-change, 26 cirrhotic) by comparing the results with those obtained by
      sequential preparative ultracentrifugation. In 14% of subjects with minimal
      change disease, the error in the estimated LDL cholesterol was 50% +/- 9% (mean
      +/- SD; range 40-59%) and was related to the degree of attendant
      hypertriglyceridemia (r = 0.98; P < 0.001). A similar degree of error was
      observed in patients with cirrhosis, despite the absence of hypertriglyceridemia;
      an abnormal VLDL cholesterol: triglyceride ratio was the contributory factor in
      the discrepancy. We conclude that, as is the case in other clinical pathologies
      in which abnormalities of lipoprotein composition have been described (e.g.,
      diabetes), the Friedewald formula to estimate LDL cholesterol may be
      inappropriate in chronic alcoholics, particularly those in whom a degree of
      hepatic dysfunction may be suspected.

PMID- 8131277
TI  - Retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha
      carotene, trans-beta-carotene, and four retinyl esters in serum determined
      simultaneously by reversed-phase HPLC with multiwavelength detection.
AB  - We describe the use of HPLC with multiwavelength detection to measure retinol,
      alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha
      carotene, trans-beta-carotene, beta-carotene, and the linoleate, oleate,
      palmitate, and stearate esters of retinol in a single 200-microL serum sample.
      The method is sensitive enough to detect individual retinyl esters in fasting
      serum from a nonhyperlipidemic population and requires only 12 min for each
      sample. Serum concentration ranges and means are reported for retinol, alpha
      tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene,
      trans-beta-carotene, and the sum of the retinyl esters from serum analyses of
      3480 participants from several different studies.

PMID- 8131278
TI  - Interference of ofloxacin with determination of urinary porphyrins.
AB  - The second-generation quinolone ofloxacin interferes with the screening test of
      porphyrins. We observed a 20-fold increase in the porphyrin concentration
      measured in urine of an ofloxacin-treated patient, compared with drug-free normal
      urine. Two other fluorinated 4-quinolones tested, norfloxacin and ciprofloxacin,
      had a less marked effect (a twofold increase), whereas the first-generation
      quinolone, nalidixic acid, did not affect the measured porphyrin concentration at
      all. The interference is probably due to the overlap in the emission fluorescence
      spectra of ofloxacin and urinary porphyrins at approximately 600 nm. To avoid a
      false-positive diagnosis of porphyria, we suggest using HPLC to separate
      ofloxacin (10-min retention time) from urinary porphyrins (which only start to
      elute at 12 min). Nonetheless, given a threefold increase in urinary porphyrins
      observed in the urine of an ofloxacin-treated patient, we also discuss a possible
      interference of the drug with the metabolism of porphyrins.

PMID- 8131279
TI  - Measuring swainsonine in serum of cancer patients: phase I clinical trial.
AB  - Swainsonine, an indolizidine alkaloid and competitive inhibitor of Golgi alpha
      mannosidase II (EC 3.2.1.114), reduces tumor growth and stimulates immune
      function in mice. On the basis of these observations, a phase I clinical trial
      was initiated to determine whether swainsonine could be administered safely to
      cancer patients. We describe a method for extraction, acetylation, and
      quantification of swainsonine in human serum samples. Methyl alpha-D
      mannopyranoside and methyl beta-D-galactopyranoside were added to serum samples
      as internal standards and, after sequential extraction of lipids and proteins
      with chloroform and acetonitrile, respectively, samples were acetylated with
      acetic anhydride and 4-dimethylaminopyridine and separated by gas-liquid
      chromatography. The identity of swainsonine and the internal standards after
      their extraction from serum and acetylation was confirmed by gas
      chromatography/mass spectrometry. Swainsonine was recovered at an efficiency of
      90%, relative to internal standards, and calibration graphs were rectilinear from
      3 to 18 mg/L with a detection limit of approximately 0.1 mg/L. The CV for
      multiple samples was < or = 6.7%. In patients receiving swainsonine (50-550
      micrograms/kg per day) continuously for 5 days by intravenous infusion, serum
      concentrations of the drug reached 3-11.8 mg/L, 100 to 400 times greater than the
      50% inhibitory concentration for Golgi alpha-mannosidase II and lysosomal alpha
      mannosidases. Accurate measurements of swainsonine in biological fluids with this
      method should facilitate further clinical studies with the drug.

PMID- 8131280
TI  - Aluminum determined in plasma and urine by atomic absorption spectroscopy with a
      transversely heated graphite atomizer furnace.
AB  - We compared a stabilized-temperature L'vov platform furnace containing an end
      heated graphite atomizer (HGA) and transverse Zeeman background-correction system
      with a side-heated furnace system (transversely heated graphite atomizer; THGA)
      containing a longitudinal Zeeman background-correction system for the
      determination of aluminum in plasma and urine. The regression statistics for the
      correlation analysis of the two systems (slope coefficient = 0.995, intercept = 
      1.710, Sy/x = 0.021 micrograms/L) indicate that the systems generate comparable
      results. The newer technology of the THGA furnace with its more uniform and
      faster heating cycle allows a lower atomization temperature for aluminum, 2200
      degrees C. Analyte carryover was significantly reduced in the THGA furnace
      system. The THGA system generates results equivalent to HGA in about one-third
      less time, thus making possible a greater throughput of samples in a busy
      laboratory.

PMID- 8131281
TI  - Measurement of gonadotropins in dried blood spots.
AB  - We describe direct immunofluorometric assays for luteinizing hormone (hLH) and
      follicle-stimulating hormone (hFSH) in fingerstick blood spots dried on filter
      paper, based on modifications of commercially available kits. Determinations are
      made from 2.5-mm-diameter discs (3 microL of dried blood) punched out from blood
      spot standards and samples. Sample dose detection limits of the assays (IU/L) are
      0.26 for LH and 0.13 for FSH, with mean interassay CVs of 11.6% (LH) and 7.8%
      (FSH) at low concentrations. Analytical recoveries of added hormone averaged 100%
      for LH and 95% for FSH. Clinical studies showed that values for blood spots (x)
      and directly assayed plasma (y) are highly correlated, so that results from blood
      spots can be converted directly to plasma equivalents, as follows: yLH = 0.07 +
      1.90 xLH, and yFSH = 0.424 + 2.207 xFSH. These gonadotropins are stable in blood
      spots for at least a year under refrigeration; LH for at least 8 weeks and FSH 6
      weeks at 22 degrees C; and both hormones for a week at 37 degrees C. These
      methods thus allow self-sampling, serial sampling, and mailing of specimens.

PMID- 8131282
TI  - Development and validation of a monoclonal antibody enzyme immunoassay for
      measuring progesterone in saliva.
AB  - A nonextraction, competitive, solid-phase enzyme immunoassay with a monoclonal
      antibody was developed and validated for measuring progesterone in saliva. The
      antibody was raised against 11 alpha-hydroxyprogesterone hemisuccinate-bovine
      serum albumin conjugate and was indirectly immobilized to the walls of microtiter
      wells. The labeled analyte (progesterone-horseradish peroxidase conjugate) was
      homologous with the immunogen. The lower detection limit (concentration
      equivalent to B0-3 SD) was 38 pmol/L of saliva sample. We validated the assay
      with studies to establish the independence of the concentration determined from
      the volume of saliva assayed, quantitative recovery of progesterone added to
      saliva, interference from possible cross-reactants, and agreement with a similar
      assay that incorporated an extraction step. In addition, we determined luteal
      phase concentrations of salivary progesterone in normal women and compared the
      results with those of an older assay involving a polyclonal antibody.

PMID- 8131283
TI  - Variability of laboratory coat resistance to blood strikethrough.
AB  - Protection from contamination by potentially infectious fluids is an increasingly
      important aspect of hospital safety programs. Technical personnel in clinical
      laboratories may handle numerous samples of human blood and other fluids daily,
      and to protect themselves against exposure to bloodborne pathogens they routinely
      wear laboratory coats. We studied the effectiveness of six disposable
      (polypropylene; either spun-bond or spun-bond/melt-blown/spun-bond construction)
      and four reusable (polyester-cotton) laboratory coats in preventing blood
      passage. Fabrics (1018 samples) were tested at six time durations (1 s-5 min) and
      five pressures [1.7-13.8 kPa (0.25-2.0 psi)]. A standard spray test used to
      evaluate resistance to wetting showed that reusable coats were less repellent
      than disposables (P < 0.05). Pressure testing showed that reusable and spun-bond
      coats allowed greater blood passage than the spun-bond/melt-blown/spun-bond.
      Laboratory coats should be chosen that have sufficient resistance to blood or
      other body fluid passage for the task performed and for the period of time used.

PMID- 8131284
TI  - Evaluating test methods by estimating total error.
AB  - A common procedure for evaluating a test method by comparison with another, well
      accepted method has been to use a repeated measurements design, in which several
      individual subjects' specimens are assayed with both methods. We propose the use
      of the intrasubject relative mean square error, which is a function of the
      intrasubject relative bias and the coefficient of variation of the test method,
      as a measure of total error. We construct for each individual subject a score
      that is based on how well an individual's estimate of total error compares with a
      maximum allowable value. If the individual's score is > 100%, then that
      individual's estimate of total error exceeds the maximum allowable value. We
      present a distribution-free statistical methodology for evaluating the sample of
      scores. This involves the construction of an upper tolerance limit to determine
      whether the test method yields values of the total error that are acceptable for
      most of the population with some level of confidence. Our definition of total
      error is very different from that defined in the National Cholesterol Education
      Program (NCEP) guidelines. The NCEP bound for total error has three main
      problems: (a) it incorrectly assumes that the standard error of the estimated
      relative bias is the test coefficient of variation; (b) it incorrectly assumes
      that the individual estimated relative biases follow gaussian distributions; (c)
      it is based on requiring the relative bias of the average individual in the
      population to lie within prescribed limits, whereas we believe it is more
      important to require the total error for most of the individuals in the
      population, say 95%, to lie within prescribed limits.

PMID- 8131285
TI  - Total discrimination of peritoneal malignant ascites from cirrhosis- and
      hepatocarcinoma-associated ascites by assays of ascitic cholesterol and lactate
      dehydrogenase.
AB  - No laboratory test completely distinguishes malignant ascites (MA) from ascites
      associated with cirrhosis and (or) hepatocellular carcinoma (A/C-HC). Ascitic
      cytology is highly specific but has a diagnostic sensitivity of only 40-60%. We
      determined 11 ascitic analytes and cytology in 58 patients with cirrhosis, 15
      with hepatocellular carcinoma, and 21 with MA (10 ovarian cancers, 4
      mesotheliomas, 6 gastrointestinal neoplasias, 1 leukemia). Ascitic total protein,
      cholesterol, pseudouridine, and lactate dehydrogenase (LD), and the ascitic:serum
      ratios of total protein and of LD showed the most significant differences between
      the two groups of patients. Stepwise multiple linear discriminant analysis
      (applying the Wilks' lambda criterion) of several variables, corroborated by the
      "jack-knife" reallocation procedure, showed that the ascitic cholesterol and
      ascitic LD association correctly identified 100% of MA and A/C-HC; cytology had a
      diagnostic specificity of 100%, but identified only 48% of MA. This association
      may represent a primary tool for the discrimination of ascites of unknown origin,
      particularly in the presence of negative cytology findings.

PMID- 8131286
TI  - Rapid screening for p53 mutations with a sensitive heteroduplex detection
      technique.

PMID- 8131287
TI  - Unexplained increase in serum digoxin: a case report.
AB  - We describe a patient with unexpectedly high serum digoxin after cardiac surgery.
      To control atrial fibrillation in the immediate postoperative period, she was
      given a brief trial of digoxin (four 0.25-mg doses) over 12 h. Serum digoxin 6 h
      later was 2.5 micrograms/L. Two days later, the patient developed ventricular
      fibrillation, which progressed to cardiac arrest. During or immediately after
      resuscitation, blood was drawn for a digoxin measurement, and the concentration
      reported was 9.3 micrograms/L; this result was verified by repeated analysis.
      Digoxin decreased rapidly and progressively to near 4.0 micrograms/L over the
      next several hours and thereafter decreased slowly to 1.0 microgram/L over the
      next 11 days, despite no digoxin being administered. The unexpectedly high
      digoxin raised questions about the accuracy of the digoxin measurement,
      particularly about the possible influence of the digoxin-like immunoreactive
      factor. Analytical approaches to distinguishing true digoxin from this factor and
      other artifacts of digoxin measurement were applied to this patient, with
      unanticipated results.

PMID- 8131288
TI  - Capillary electrophoresis compared with silver staining of polyacrylamide gels
      for quantification of PCR products.

PMID- 8131289
TI  - Factitiously low recoveries of urea in control sera by the Kodak Ektachem method.

PMID- 8131290
TI  - Improved HPLC determination of 5-S-cysteinyldopa in serum.

PMID- 8131291
TI  - Free triiodothyronine in hypothyroidism and in nonthyroidal illness.

PMID- 8131292
TI  - Colorimetric quantification of urinary iron during deferoxamine therapy.

PMID- 8131294
TI  - Selecting appropriate quality-control rules.

PMID- 8131293
TI  - Therapeutic monitoring of sertraline.

PMID- 8131295
TI  - "Critical difference" and biological variation of serum triglycerides.

PMID- 8131296
TI  - Effects of sucrose addition on recovery of lipoprotein(a) from lyophilized
      preparations.

PMID- 8131297
TI  - Cowden syndrome: report of a large family with macrocephaly and increased
      severity of signs in subsequent generations.
AB  - We report Cowden syndrome in a large four-generation family, paying special
      attention to the apparently greater severity and earlier onset of signs and
      symptoms in subsequent generations. Macrocephaly was present in all affected
      individuals and was markedly progressive in three of six affected children of the
      fourth generation, and associated with slight to moderate delay in psychomotor
      development.

PMID- 8131298
TI  - Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin
      expression.
AB  - Clinical features and histological findings in two sibs who died from restrictive
      dermopathy in the neonatal period are described. Fibroblasts cultured from a skin
      biopsy from the second sib and fibroblasts from normal neonatal skin were studied
      using monoclonal antibodies to visualise integrin subunits by
      immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased
      expression of the alpha-1 and alpha-2 subunits of integrin, those responsible for
      collagen binding. The increase was not matrix dependent. Integrins may play an
      important role in tissue differentiation, and our findings support the hypothesis
      that restrictive dermopathy is a disorder of skin differentiation.

PMID- 8131299
TI  - Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting
      enzyme and myocardial infarction.
AB  - Male (n = 185) and female (n = 49) survivors of myocardial infarction (MI) below
      56 and 61 years of age, respectively, were compared to 366 controls with respect
      to distribution of genotypes in an insertion/deletion (ID) polymorphism at the
      angiotensin I-converting enzyme (ACE) locus. The frequency of the DD genotype
      (homozygosity for the deletion allele) was significantly lower among male
      patients than controls (22.7% versus 34.9%, p = 0.011). In a "low-risk" group,
      defined as having less than the sex-specific, age-adjusted median values of body
      mass index (BMI) and apolipoprotein B (apoB), respectively, and absence of
      treatment with lipid-lowering drugs, the prevalence of the DD genotype was not
      statistically different between male patients and controls. In a male "high-risk"
      group (those individuals who had not been defined as "low-risk" subjects), the
      prevalence of the DD genotype was 20.9% in patients and 38.3% in controls (p =
      0.002). In women, no significant differences in genotype frequencies between
      patients and controls were found in the whole sample or in any subgroup. These
      results appear to be at variance with data reported recently by Cambien et al.
      (1992). The difference may be due to chance, undetected selection biases,
      different gene-environment interactions between Norway and France or Ireland, or
      to preferential loss of DD individuals in our male "high-risk" group.

PMID- 8131300
TI  - Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting
      enzyme and parental history of myocardial infarction.
AB  - One hundred and eighty-one male and 48 female myocardial infarction (MI)
      survivors and 172 male and 194 female controls were studied with respect to a
      possible association between premature parental MI (before age 61 years in
      mothers and/or before age 56 years in fathers) and an insertion/deletion (I/D)
      polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). In the
      total series, the frequency of premature parental MI was 14% in the DD
      (homozygotes for the deletion (D) allele) genotypic group, 10.6% in the ID
      (heterozygotes) genotypic group and 6.1% in the II (homozygotes for the insertion
      (I) allele) genotypic group. In all males (male MI survivors and male controls
      combined), and in the total series, there was a significant excess of DD
      individuals as compared to II individuals among those with a parental history of
      premature MI (odds ratio 3.1 (p = 0.03) and 3.1 (p = 0.009), respectively). The
      ACE polymorphism may be an important genetic marker of MI risk and contribute to
      clustering of premature MI in families.

PMID- 8131301
TI  - Immunofluorescence imaging diagnosis of Fabry heterozygotes using confocal laser
      scanning microscopy.
AB  - An immunofluorometric method was developed for the semiquantitative determination
      of trihexosylceramide in cultured fibroblasts from Fabry disease patients, using
      a laser scanning confocal imaging system. The accumulated glycolipid was detected
      as granular inclusions in the cells. Heterozygote identification was achieved
      both by counting of immunoreactive cells and by measuring the relative
      fluorescence intensity with a digital imaging system.

PMID- 8131302
TI  - Adenine for guanine substitution -78 base pairs 5' to the apolipoprotein (APO) A
      I gene: relation with high density lipoprotein cholesterol and APO A-I
      concentrations.
AB  - A common mutation, adenine (A) for guanidine (G) substitution (G/A) has been
      located -78 bp 5' to the apo A-I gene. This region has been shown to be involved
      in the transcriptional regulation of the apo A-I gene. Previous studies have
      shown that this mutation is associated with altered high density lipoprotein
      cholesterol (HDL-C) levels, although these findings have not been consistent. We
      have studied the frequency of this mutation in 125 subjects (60 males and 65
      females) selected because they had HDL-C levels below the 25th (low HDL) or above
      the 75th (high HDL) percentile of the population distribution. The presence of
      the mutation was detected by Msp I digestion of a 259 bp fragment of PCR
      amplified DNA. The allele frequency was similar in both groups (0.20 for the
      lowest HDL group and 0.28 for the highest HDL group, p > 0.05), although a non
      significant trend was observed in a higher frequency of the A/A genotype in the
      highest HDL females (17.5%) vs only 6.7% in the lowest HDL female group. In
      conclusion, in this population the G/A mutation was not significantly associated
      with HDL-C or apo A-I plasma levels.

PMID- 8131303
TI  - A mild form of mucolipidosis type III in four Baluch siblings.
AB  - Four Baluch siblings with mucolipidosis type III (pseudo-Hurler polydystrophy)
      are described. The patients had features commonly found in mucolipidosis III,
      including claw hands, joint stiffness, aortic valve involvement and radiological
      dysostosis multiplex. However, intelligence was normal, there were no eye
      abnormalities on slit-lamp examination and skin elasticity was normal. Many
      lysosomal enzymes were elevated in serum and diminished in cultured fibroblasts,
      although the findings for beta-galactosidase were atypical. Assays for the two
      enzymes involved in formation of the phosphomannose recognition marker revealed
      normal activity of the phosphotransferase with alpha-methylmannoside as an
      acceptor, and normal activity of the phosphodiester glycosidase. Metabolic
      labelling of fibroblasts with 32P followed by immunoprecipitation of cathepsin D,
      electrophoresis and fluorography showed that this enzyme was not labelled in the
      patients' cells, although some label was detected in the secreted precursor
      polypeptide. The data are consistent with the assumption that activity of the
      phosphotransferase is low towards lysosomal enzymes as substrates, and that the
      patients belong to complementation group C.

PMID- 8131304
TI  - Frequency of the arylsulphatase A pseudodeficiency allele in the Spanish
      population.
AB  - Pseudodeficiency in arylsulphatase A (ASA) is a relatively frequent condition in
      healthy individuals. It produces a reduction in enzyme activity similar to that
      found in metachromatic leukodystrophy (MLD). Unambiguous discrimination between
      the two conditions cannot be achieved through conventional enzyme activity
      assays. A PCR method has been developed which detects the pseudodeficiency (pd)
      allele using a single pair of primers encompassing the mutation site and hair
      follicles as the source of DNA. The frequency of this allele in the Spanish
      population has been evaluated and correlations between different genotypes and
      ASA activity levels have been established. Ten out of 55 individuals were
      heterozygous for the ASA pd allele, while two were homozygous. The allele
      frequency was thus 12.7%.

PMID- 8131305
TI  - 11q trisomy detected by fluorescence in situ hybridization.
AB  - A patient with psychomotor developmental delay, multiple minor anomalies,
      congenital heart disease and left inguinal hernia is reported. His karyotype was
      45,X/46,X,+mar (3:37 cells), and the marker chromosome was identified as
      t(Y;11)(q12;q14?) using fluorescence in situ hybridization and fluorescent
      chromosome painting. He was diagnosed as mosaic for de novo 11q trisomy.

PMID- 8131306
TI  - Disease profile of 400 institutionalized mentally retarded patients in Kuwait.
AB  - In this preliminary report we summarize the results of a 4-year multidisciplinary
      systematic, etiological clinicogenetic survey of 400 institutionalized mentally
      retarded patients in Kuwait. All had an intelligence quotient below 50. A
      constitutional disorder, as the direct cause of the mental retardation, was found
      in 203 patients (50.75%)): a chromosomal abnormality in 37 (9.25%), Mendelian
      disorders in 137 (34.25%), MCA/MR in 22 (5.55%) and CNS malformations in 7 cases
      (1.75%). In 157 patients (39.35%) a pre-, peri or postnatal cause was
      ascertained. No etiological diagnosis was detected in 40 patients (10%). A
      detailed analysis of the "disease profile" is given and compared with the results
      of previous diagnostic genetic surveys among different institutionalized mentally
      retarded populations in Western and developing countries.

PMID- 8131307
TI  - De novo interstitial deletion of the long arm of chromosome 3:
      46,XX,del(3)(q25.1q26.1).
AB  - A girl with an interstitial deletion of chromosome 3 is presented. The facial
      resemblance to an earlier reported patient with a shared breakpoint is addressed.

PMID- 8131308
TI  - Twins and their mildly affected mother with Weaver syndrome.
AB  - A pair of twins, a brother and sister, with the complete form of Weaver syndrome
      (overgrowth, macrocephaly, facial, skeletal, nail and feet anomalies) and their
      mildly affected mother are reported, suggesting autosomal dominant inheritance.
      They all have plantar and palmar hyperhydrosis and twins also have nail
      dysplasia, symptoms which have not yet been described in this syndrome.

PMID- 8131309
TI  - Is endometriosis a disease?
AB  - Recent comparative studies and developments in our understanding of the
      pathogenesis and pathophysiology of endometriosis have led to increasing doubts
      about whether it should always be considered a disease. Widespread use of
      laparoscopy for gynaecological investigation and treatment, recognition of non
      pigmented lesions which are more active than classical implants, and the
      documentation of microscopic lesions in visually normal peritoneum, have all
      resulted in an increase in the frequency with which endometriosis is diagnosed.
      Recent studies suggest a prevalence of up to 80% in women complaining of
      infertility or pelvic pain, but also in up to 22% of fertile asymptomatic women
      undergoing sterilization. Perhaps it is a normal physiological variant, being
      present in such a high proportion of the population. Circumstantial evidence
      suggests this may be so, and the results with placebo treatment in controlled
      trials suggest that endometriosis is self-limiting and will regress or disappear
      spontaneously in 58% of women. The frequency and severity of symptoms which are
      often presumed to result from endometriosis do not correlate with the extent or
      site of lesions. Most women are pain-free. There is no dysmenorrhoea in up to
      77%, no dyspareunia in up to 70%, and no pelvic pain at all in up to 61% of women
      with endometriosis. The pathophysiology of pain related to endometriosis is not
      understood. There is no medical or conservative surgical treatment that is wholly
      effective for symptom relief, and there is considerable placebo benefit. All
      treatments have risks or side-effects, and recurrent symptoms will develop in up
      to 45% of women within 5 years. For these reasons treatment should only be used
      where endometriosis fulfils the criteria of a disease, showing signs of
      progression with tissue damage or physiological disturbance. Asymptomatic
      endometriosis without tissue damage should not be considered a disease and should
      not be treated. Treatment of pain associated with minor endometriosis, or
      prophylactic treatment to prevent progression, must be regarded as empirical and
      not the specific requirement to control what is a questionable disease.

PMID- 8131310
TI  - Menstruation as the pelvic aggressor.
AB  - Cumulative evidence supports the concept of retrograde menstruation being a
      pelvic aggressor as it contributes to both the development of endometriosis and
      related symptoms such as dysmenorrhoea and infertility. A major problem in
      studying the association between these entities (retrograde menstruation,
      endometriosis, dysmenorrhoea and infertility) is the lack of an accurate method
      to quantify the amount of retrograde menstruation.

PMID- 8131311
TI  - Endometriosis: the host response.
AB  - There is abundant evidence of altered immune function in endometriosis. The task
      that remains is to attempt a synthesis from the accumulated data, to try to make
      some sense of the observed phenomena and to fit them into a conceptual framework;
      this might permit the formulation and testing of hypotheses. Evidently, eutopic
      endometrium does not engender an immune response in normal subjects, otherwise
      the endometrium would be subject to autoimmune destruction. It has also been
      established that the overwhelming majority of women regurgitate menstrual debris
      into the peritoneal cavity. Why does this lead to endometriosis in some, but not
      in others? There are several possible explanations. The uterus might act as a
      privileged site, i.e. be exempt from immune effector mechanisms. This would
      certainly be conducive to the reproductive goal, the survival of the fetal
      allograft. Endometrium would then not enjoy the immunologic tolerance of most
      other tissues, and upon leaving the uterus and entering an immunocompetent
      environment would be subject to immune attack. In normal subjects, this could
      consist of elimination of menstrual debris without further sequelae. An altered
      response, characterized by the production of antibody that could mask receptors
      for cytotoxic or phagocytic effector cells, would permit persistence of ectopic
      endometrium. The alternative to this hypothesis is that the uterus is not a
      privileged site, and that the organism is normally tolerant to endometrial
      antigens. Menstrual debris would be eliminated intraperitoneally without loss of
      tolerance due to the presence of homeostatic mechanisms including suppressor T
      cells and suppressive cytokines. In endometriosis, this tolerance breaks down, as
      is the case in several autoimmune disorders, causing a chronic inflammatory
      response with the release of toxic factors and, eventually, peritoneal scarring.
      Finally, the role of cell adhesion molecules, including the integrins, is only
      just being explored. The behaviour of these molecules in ectopic endometrium
      differs from that in eutopic endometrium, and it remains to be seen whether
      regurgitated endometrial debris from normal subjects is different from that of
      endometriosis sufferers. It seems that this will be an area of intense
      investigation in the immediate future.

PMID- 8131312
TI  - Markers for endometriosis.
AB  - Screening for endometriosis is subject to general rules. The two most important
      conditions, i.e. the disorder should be well-defined and serious, and there must
      be an effective way to treat or prevent it through screening, are not satisfied
      for endometriosis. Given the lack of understanding of the pathogenesis of this
      disease and the disreputable evidence of treatment effectiveness, other criteria
      for worthwhile screening programmes, such as prevalence, cost effectiveness and
      screening test performance, cannot be evaluated. Markers may be applied in the
      diagnostic process in the individual patient, although it should be realized that
      the best results will be obtained in patients with advanced disease, in whom
      routine pelvic examination will establish the diagnosis on purely clinical
      grounds anyway. The development of appropriate tissue markers may in the future
      shed more light on the intricate mechanisms involved in the pathogenesis of
      endometriosis.

PMID- 8131313
TI  - Appearances of endometriosis.

PMID- 8131314
TI  - Classification of endometriosis.
AB  - A perfect endometriosis classification should be a common language and an expert
      system which helps the gynaecologist to decide the treatment of each patient. The
      staging of endometriosis is not a new idea; the first classification based on
      histologic criteria was presented in 1941. Since this initial attempt, several
      classifications have been proposed. These various systems are reviewed in terms
      of their advantages and defects. The revised American Fertility Society (AFS)
      endometriosis classification system is now accepted worldwide as the
      endometriosis international language. Laparoscopic staging and measurement
      techniques are presented and discussed. In recent reports, changes to the revised
      AFS classification have been proposed, including a better description of atypical
      and deep infiltrating peritoneal implants, and a stage V for patients with
      bilateral, extensive, dense adhesions. Despite its well-known advantages, the
      revised AFS classification cannot be used as a satisfactory expert system. A
      better understanding of endometriosis is required to improve the present system.
      Scientifically based scores for each lesion and a marker for disease 'activity'
      will be fundamental to a classification which will act as a valuable expert
      system and become the endometriosis classification of the twenty-first century.

PMID- 8131315
TI  - Endometriosis and pelvic pain.
AB  - The majority of patients with pain associated with endometriosis will obtain
      benefit from the many and varied therapies available for the treatment of
      endometriosis. The minority who fail to obtain relief from the conventional
      therapies may obtain benefit from referral to a pain clinic.

PMID- 8131316
TI  - Endometriosis-associated infertility.
AB  - Despite intense clinical interest and increasingly sophisticated diagnostic
      techniques, we know surprisingly little of the relationship between endometriosis
      and infertility or the mechanism of infertility in these couples. No therapy
      specifically directed toward the ectopic endometrial implants, medical or
      surgical, has been demonstrated to improve the likelihood of pregnancy for
      couples with endometriosis-associated infertility. This is consistent with the
      observation that, in the absence of mechanical distortion of the pelvic viscera,
      no therapy directed against the implants improves the likelihood of pregnancy in
      these couples. The reason for this lack of progress is most probably that the
      mechanism of infertility in these couples remains to be determined. At present,
      it would be more accurate to say that these couples have unexplained infertility.
      The most promising therapeutic approach is to treat women with endometriosis
      associated infertility with a non-specific cycle fecundity enhancing technique.
      Typically this is one of the newer assisted reproductive technologies such as
      controlled ovarian hyperstimulation with intrauterine insemination of capacitated
      sperm. Since the fecundity of many of the women with endometriosis in the later
      reproductive years is rapidly declining, this may represent their most cost
      effective option for establishing a pregnancy. Only with further effort directed
      towards determining the mechanisms of infertility in these couples will a more
      effective therapy be forthcoming.

PMID- 8131317
TI  - Endometriosis: medical therapy.
AB  - The management of women with endometriosis is complex and necessitates
      individualization of patient care. The most commonly used medical therapies are
      danazol, GnRH agonists, medroxyprogesterone acetate and gestrinone. Studies to
      date have shown these drugs to have equal efficacy in terms of reduction in
      laparoscopic score and relief of symptoms. However, their side-effects make them
      unsuitable for long-term use. The addition of low dose hormone replacement
      therapy to GnRH agonist regimens may allow prolonged use but the current cost of
      these agents is high. Low dose oral contraceptive pills deserve further
      investigation. The role of medical treatment for women with endometriosis and
      infertility is controversial. There is no place for hormonal therapy in such
      women with stage I or II disease. When expectant management fails, gamete
      intrafallopian transfer offers excellent results. For those with stage III or IV
      disease, surgery is preferable with adjunctive medical therapy in selected cases.
      If pregnancy does not ensue, in vitro fertilization and embryo transfer are the
      next line of management, and results are optimized by prior medical therapy and
      aspiration of endometriomas. Major advances have been made in the medical
      management of endometriosis. However, current treatment strategies are
      ineffective in eliminating the disease in most women. New approaches are required
      in both basic and clinical research in order to finally eradicate this often
      devastating disease.

PMID- 8131318
TI  - Endoscopic surgery.

PMID- 8131319
TI  - Endometriosis: radical surgery.
AB  - Radical ablative surgery for endometriosis is indicated chiefly for symptoms of
      pain that fail to respond to conservative treatment. The sites of involvement
      must be carefully assessed and surgery planned taking account of the wishes of
      the patient concerning her fertility. Procedures include oophorectomy, salpingo
      oophorectomy, hysterectomy, appendicectomy, and the excision of deeply
      infiltrating endometriosis possibly involving bowel resection. The most important
      arbiter of therapeutic success is the removal of the ovaries, hysterectomy and
      bilateral salpingo-oophorectomy offering the ultimate cure for this chronic
      condition. Whereas laparotomy has been the traditional approach for most of these
      procedures, vaginal and laparoscopic surgery are modern alternatives for many of
      these cases offering important advantages in terms of reduced postoperative
      discomfort, shorter hospitalization, faster recovery and a superior cosmetic
      result. Preoperative and postoperative medical therapy has a limited role in
      surgery, whereas postoperative hormone replacement therapy after bilateral
      oophorectomy is generally recommended.

PMID- 8131320
TI  - The rise of academic orthopaedic surgery during the past 44 years.
AB  - In accepting this invitation to write a prefatory chapter as a mini professional
      autobiography, it has become all too obvious that this has touched a few nerve
      endings that had healed many years ago. Contemplating personal experiences,
      thoughts, and philosophies and then writing them should have a purpose. During
      these past 44 years, I have had the good fortune to share in the breaking away of
      orthopaedics as a clinical practice, into an academic and scientific subject.
      Such a radical and difficult birth has been in the presence of many able and good
      fellow travellers and perhaps, therefore, may serve as a guide for the future by
      those who care to follow. The mixture of clinical practice with caring for
      people, teaching, and research has to be bound securely together by academic
      professors. This has presented the greatest challenge to me and certainly the
      greatest difficulty, because we have all faced criticism, not always
      constructive, from these three separate cultures. Even so, our responsibility has
      been to integrate science and medicine sensibly. Richards described universities
      as being places of high technology and remoteness from reality. In my experience
      having spent most of my professional life in British and American universities,
      the reality has always been too near and real.

PMID- 8131321
TI  - Congenital bilateral absence of the acromion. A case report.
AB  - Complete bilateral absence of the acromion, a condition not previously reported
      by others, was discovered in a 31-year-old housewife who had shoulder pain.
      Clinically, no abnormal physical sign was noted in the patient except for mild
      superior translation of the humeral heads. Radiographs showed bilateral absence
      of the lateral aspect of each scapular spine and acromion. The lateral ends of
      both clavicles were hypertrophied with convex and blunt margins. Even in the
      absence of the acromion, there was no significant clinical dysfunction of the
      shoulder joint.

PMID- 8131322
TI  - Coracoid process fracture combined with acromioclavicular dislocation and
      coracoclavicular ligament rupture. A case report and review of the literature.
AB  - A coracoid process fracture associated with acromioclavicular joint dislocation
      and with rupturing of the coracoclavicular ligaments of an adult has been
      reported only once in the literature. This report adds another unusual case to
      the literature to reemphasize the importance of recognizing this unusual lesion.
      Two separate mechanisms--direct trauma to the shoulder girdle and sudden pull on
      the coracoid process by the conjoined tendons of short head biceps and
      coracobrachialis muscles--appear to be responsible for this unusual triple
      lesion. Open reduction with coracoid screw and acromioclavicular fixation,
      combined with an All-dredge repair to replace the ruptured coracoclavicular
      ligaments, resulted in an excellent outcome.

PMID- 8131323
TI  - Herbert screw fixation of a capitellum fracture. A case report and review.
AB  - Fractures of the capitellum frequently result in significant osteochondral
      fragments that require internal fixation to restore the anatomic integrity of the
      elbow joint. Precise reduction is mandatory to maximize articular congruency and
      diminish the potential for arthrosis. Successful repair of a Type I capitellum
      fracture in a 54-year-old-woman was accomplished using the Herbert bone screw.
      This alternative treatment modality allowed for efficient and rigid fixation with
      less soft-tissue dissection and articular penetration than previously reported.

PMID- 8131324
TI  - The incidence of fractures of the clavicle.
AB  - The age- and gender-specific incidences were calculated in 2035 cases of fracture
      of the clavicle. The fractures were classified in three groups according to the
      Allman system. Each group was further divided into undisplaced and displaced
      fracture subgroups, with an extra subgroup of comminuted midclavicular fractures
      in Group I. Seventy-six percent of the fractures were classified as Allman Group
      I. The median age in this group was 13 years. There were significant differences
      in age- and gender-specific incidence between the undisplaced, displaced, and
      comminuted fracture subgroups. Twenty-one percent were classified as Allman Group
      II. The median age of the patients was 47 years, and there was no difference in
      age between the undisplaced and displaced fracture subgroups. Three percent were
      classified as Allman Group III, and the median age of the patients in this group
      was 59 years. All three groups were characterized by a significant preponderance
      of men, and there was a significant increase in the incidence of clavicular
      fracture, both overall and sports-related, between 1952 and 1987.

PMID- 8131325
TI  - Surgical treatment of mallet finger fractures by tension band technique.
AB  - A retrospective review was performed of 19 patients with irreducible mallet
      finger fractures after failed splinting. The patients were treated with open
      reduction and a tension band technique. Follow-up results were available for 18
      patients (95%) at an average 8.2 years postoperatively. Eighty-nine percent of
      patients had no clinical mallet deformity, troublesome pain, or major functional
      disability. Distal interphalangeal range of motion averaged 1 degree
      hyperextension to 69 degrees flexion. All fractures healed with a congruent
      articular surface. Minor nonmechanical complications were encountered in 11% of
      cases in which a suture was used as the tension band material. Successful
      treatment may thus be achieved surgically in this select subset of mallet finger
      fractures when this technique is employed.

PMID- 8131326
TI  - Acute median neuropathy after wrist trauma. The role of emergent carpal tunnel
      release.
AB  - Ten cases of acute carpal tunnel syndrome (ACTS) and six cases of nerve contusion
      were identified in patients with acute median neuropathy associated with blunt
      wrist trauma. The patients with ACTS initially had normal sensation and
      subsequently developed objective sensory loss (2-point discrimination greater
      than 15 mm) in the median nerve distribution associated with severe wrist pain.
      Patients with nerve contusion injuries had immediate sensory loss and symptoms
      were nonprogressive. Wick catheter measurements of the carpal canal pressure were
      used in seven patients to help distinguish ACTS (pressure greater than 40 mm Hg)
      from nerve contusion. The interstitial carpal tunnel pressure was elevated an
      average of 52 mm Hg in four of five patients with ACTS but was normal in two
      patients with nerve contusion. Four of five patients who underwent carpal tunnel
      release within 40 hours of the onset of numbness had normal 2-point
      discrimination within 96 hours. The results of this study and review of the
      literature reflect the urgency of carpal tunnel release in ACTS. Neuropathy,
      secondary to nerve contusion without coexisting ACTS, may be treated initially by
      observation. Acute carpal tunnel syndrome must be distinguished from nerve
      contusion as a cause of acute posttraumatic median neuropathy.

PMID- 8131327
TI  - Hip fusion in young adults. Using a medial displacement osteotomy and cobra
      plate.
AB  - Eight consecutive patients, mean age 17.25 years, underwent a medial displacement
      osteotomy and hip arthrodesis with a nine-hole Cobra plate. A transverse
      innominate osteotomy facilitated medial displacement of the femoral head and
      acetabulum. Alignment of the lower limb at 25 degrees flexion, neutral abduction,
      and neutral rotation was assisted by a long-limbed protractor and Steinmann pins
      placed in both anterior superior iliac spines. The greater trochanter was
      reattached to the Cobra plate so that hip abductor function could be restored
      should the fusion ever be converted to an arthroplasty. No postoperative
      immobilization was required. All patients had radiographic evidence of union by
      12 months. One patient had a postoperative brachial plexus neuropraxia that
      resolved at three months. One patient required an ipsilateral femoral lengthening
      for limb-length inequality secondary to collapse of his femoral head before hip
      fusion. At a mean follow-up interval of 2.8 years (range, one to 4.5 years), all
      patients had significant improvements in pain (p < 0.05), function (p < 0.01),
      and gait (p < 0.01). The average preoperative Harris Hip Score of 45 points +/- 8
      points (mean +/- SEM) improved to 84 points +/- 2 points (p < 0.01).

PMID- 8131328
TI  - Evolution of aggressive granulomatous periprosthetic lesions in cemented hip
      arthroplasties.
AB  - The authors analyzed the histologic findings from material retrieved during 17
      revision operations from 15 patients who had cemented total hip arthroplasty or
      hemiarthroplasty. In 13 patients, the indication for revision was aseptic
      loosening. In four patients, technical error during implantation of the
      prostheses made revision necessary. The histologic pictures in the loosened and
      nonloosened prostheses were similar, characterized by the presence of a synovial
      like membrane at the site corresponding to the hip joint cavity or abutting the
      implant, underneath which were found aggregates of histiocytes and foreign-body
      giant cells within a dense fibrous matrix. The main foreign material in all
      patients consisted of fine granules or larger cement particles. A few
      polyethylene fibers were also observed in some patients. Metal deposits were
      found in three patients with titanium alloy implants and extensive loosening. The
      most interesting aspect of this series was the opportunity it provided to study
      the progressive development of the synovial-like membrane and the first
      appearance of the cement granulomas in non-loosened cases. The first signs of the
      synovial membrane appeared 2.5 months postoperatively, whereas the first cement
      debris were observed as early as seven months after the implantation of the
      prosthesis. The hip joint newly formed membrane in the nonloosened cases did not
      differ histologically from that in the loosened cases. Because the histology of
      loosened and technically poorly placed nonloosened-prostheses are the same, the
      authors believe that the mechanism of failure associated with cell macrophage
      mediated osteolysis may be the same.

PMID- 8131329
TI  - Anterior spinal fusion. A preliminary communication on the radical treatment of
      Pott's disease and Pott's paraplegia. 1956.

PMID- 8131330
TI  - An analysis of the head-neck taper interface in retrieved hip prostheses.
AB  - The purpose of this study was to examine the mating surfaces of femoral heads and
      stems for evidence of corrosion, and to evaluate the quality of the taper lock of
      modular hip prostheses. Forty-eight implants with three different designs were
      evaluated. Group I (26 implants) had a cobalt alloy head and cobalt alloy stem.
      Group II (ten implants) had a cobalt alloy head and a titanium stem. Group III
      (12 implants) had a cobalt alloy head with a titanium stem that was coupled in
      the factory via a shrink fit. The implants were examined under light microscopy
      and scanning electron microscopy. In cases where the femoral head was still
      assembled to the stem, pull-off testing was performed using an MTS machine. The
      average failure load for the pull-off tests for each group of prostheses was as
      follows: Group I (nine implants) 3,003 N +/- 623 N; Group II (six implants) 4453
      N +/- 570 N; and Group III (12 implants) 6859 N +/- 3525 N. The Group III
      implants required a significantly greater pull-off force than those in Group I (p
      = 0.002). There was no evidence of corrosion in Group I. In Group II, crevice
      corrosion was noted in one taper interface and there was fretting in two other
      tapers. No corrosion was noted in Group III. Improving the tolerances of the
      mating surfaces may be a key factor in preventing corrosion. This would not only
      increase the forces that are necessary to debond the matting surfaces, but also
      decrease corrosion by reducing micromotion and fluid at the taper interface.

PMID- 8131331
TI  - Total articular replacement arthroplasty. A three- to ten-year case-controlled
      study.
AB  - One hundred eighty-four cemented primary total articular replacement arthroplasty
      (TARA) resurfacing total hip procedures were performed by a single surgeon from
      1981 to 1985. One hundred seventy-four hips had a mean follow-up period of eight
      years (range, 3.5-10.4 years). Osteoarthrosis was the predominant diagnosis
      (79%). Failure was defined as a hip needing additional surgery because of an
      implant failure and occurred in 13.2% of the patients. No statistically
      significant difference was found between preoperative etiology, patient gender,
      or the side of the hip involved between the revised and unrevised patients. The
      revised group was seven years younger at the time of TARA implantation than the
      group that was not revised (55.7 versus 65.3 years), with significance to the p <
      0.01 level. Survival analysis demonstrated an 87.1% chance of survival at seven
      years, decreasing to 84.5% at ten years. The cemented TARA hip replacement has a
      better intermediate-to long-term success than other resurfacing designs reported
      using cemented fixation. However, this does not compare favorably with the
      longevity of cemented Charnley total hip replacements reported at similar
      intervals.

PMID- 8131332
TI  - Ipsilateral knee injury with femoral fracture. Examination under anesthesia and
      arthroscopic evaluation.
AB  - Forty adults with closed diaphyseal femoral fractures and no previous knee injury
      were prospectively studied to determine the incidence of concomitant ipsilateral
      extra- and intraarticular knee injury. After intramedullary nailing, examination
      under anesthesia and arthroscopy were performed. The mechanism of injury was high
      energy trauma. Femoral fixation included 30 interlocked nails. The results of the
      examination showed laxity > Grade I in 52.5% of the patients. Significant
      arthroscopic findings included 19 partial (48%) and two complete (5%) anterior
      cruciate injuries; two partial (5%) and one complete (2.5%) posterior cruciate
      injuries; and five medial (12%) and eight lateral (20%) meniscus tears.
      Significant arthroscopic findings (anterior cruciate ligament or posterior
      cruciate ligament injuries, meniscal tear, osteochondral fracture) were noted in
      conjunction with effusion or laxity > Grade I in more than half of the group, and
      such findings were present in one third despite absence of effusion or laxity.
      This study documented the incidence and array of findings noted at arthroscopy.
      In all, 22 patients (55%) had significant arthroscopic findings. A high incidence
      of knee injuries, including many that were occult, occurred in conjunction with
      ipsilateral femoral shaft fractures. Based on these findings, the authors
      recommend a high index of suspicion for coexisting knee injuries with ipsilateral
      femoral fracture and use of appropriate diagnostic and therapeutic measures.

PMID- 8131333
TI  - Surgical treatment of diffuse pigmented villonodular synovitis of the knee.
AB  - Twenty-five cases of diffuse pigmented villonodular synovitis of the knee in 23
      patients were reviewed to determine the results of surgical treatment. All the
      cases met strict histologic criteria for diagnosis. Long-term clinical follow-up
      data (average, 58 months) were available for all patients. One case for a patient
      who was treated by marginal excision recurred within one year. All other cases
      (initial and recurrent) were treated by total synovectomy, preserving the
      functional integrity of the knee. Proximal extensor realignments were performed
      in patients in which chronic distention had caused a redundancy of retinacular
      tissues. Adhesions, an early complication in eight patients, responded well to
      closed manipulation and did not adversely affect long-term functional outcome.
      The outcome was excellent in seven and good in 16 the patients. Two of the
      patients have had recurrences but have not had another operation. Using this
      technique, the recurrence rate (8%) and morbidity are significantly lower than
      those reported previously.

PMID- 8131334
TI  - Early postoperative ankle exercise. A study of postoperative lateral malleolar
      fractures.
AB  - Fifty-three patients with dislocated lateral malleolar fractures were randomly
      selected after operation for either active ankle movement and weight bearing in
      an orthosis or no ankle movement but weight bearing in a walking cast. At follow
      up examinations after three, six, and 18 months, no differences were found
      between the groups except for a better linear analogue scale result at three
      months for the orthosis group. Active ankle movements do not improve the
      rehabilitation of surgically treated lateral malleolar fractures.

PMID- 8131335
TI  - The heel-pad compressibility.
AB  - Heel-pad thickness and compressibility were studied in the feet of 400 normal
      subjects by loaded and unloaded lateral radiographs. The normal unloaded heel-pad
      thickness was 18.70 +/- 2.46 mm. The thickness was greater in men than in women
      and increased with age. The heel-pad compressibility index was 0.53 +/- 0.09. The
      compressibility increased with age, but there was no significant difference with
      gender. An increase in body weight led to an increase in heel-pad thickness and
      loss of elasticity.

PMID- 8131336
TI  - Foot and ankle surgery in patients with psoriasis.
AB  - During a 15-year period, 17 patients with psoriatic arthritis had 27 foot and
      ankle operations. The most common operation was forefoot arthroplasty. The stage
      of psoriatic skin involvement and the pattern of radiographic changes in the foot
      and ankle joints were evaluated, and the factors thought to influence
      perioperative outcome were reviewed. The complications were Koebner's phenomenon
      (or isomorphic response), infection, and nonunion, which were uncommon. The
      features predicting outcome of diagnosis and treatment were not identified.

PMID- 8131337
TI  - The fate of anterior vertebral bone grafts in patients irradiated for neoplasm.
AB  - Perioperative irradiation is often used with anterior decompression and vertebral
      interbody fusion for the treatment of spinal neoplasms, yet little is known
      regarding the healing potential of these grafts. This review of 25 patients with
      neoplasm who had anterior vertebrectomy, bone strut insertion, and perioperative
      irradiation was performed to look specifically for evidence of radiographic
      fusion as determined by plain radiographs, tomograms, or computed tomography
      reconstruction. Four of 25 patients (16%) were judged to have a pseudarthrosis.
      All four pseudarthrosis patients but only four of 21 fusion patients had 4000 cg
      or more of irradiation, a statistically significant difference. There was a trend
      for lumbar lesions to have a higher risk for nonunion. Concomitant posterior
      stabilization did not necessarily prevent pseudarthrosis. Two iliac strut grafts
      with a pseudoarthrosis developed late fracture and one went on to collapse into
      kyphosis. The pseudarthrosis rate of anterior vertebral strut grafts in the face
      of irradiation for tumor is relatively high, and late graft fracture can occur if
      pseudarthrosis develops. Probable risk factors include irradiation greater than
      4000 cg and lumbar lesions. Posterior stabilization to protect the graft may be
      warranted in the highest-risk patients.

PMID- 8131338
TI  - Clinical presentation of alveolar soft-part sarcoma.
AB  - Alveolar soft-part sarcomas are rare and seldom considered in the differential
      diagnosis of a soft-tissue mass. Thus, early clinical recognition can be elusive.
      The authors have identified several clinical and radiographic features of
      alveolar soft-part sarcoma, emphasizing the importance of magnetic resonance
      imaging in the preoperative diagnostic and staging workup. Accurate diagnosis and
      treatment of this unusual tumor requires clinical suspicion and clinicopathologic
      correlation with appropriate radiographic studies. If the clinical or
      radiographic interpretation is equivocal, early biopsy is essential to
      differentiate alveolar soft-part sarcoma from arteriovenous malformation.

PMID- 8131339
TI  - Allograft bone in the treatment of desmoplastic fibroma. A case report.
AB  - A 17-year-old girl had a desmoplastic fibroma of the distal femur. This rare
      tumor is managed by surgery alone and requires a marginal to wide resection
      because of its high risk of local recurrence. Had the tumor invaded into the
      epiphysis and marginal resection, it would have resulted in loss of articular
      femoral condyle. It was treated by en bloc proximal resection with distal
      intralesional curettage and anatomic specific allograft femoral replacement.
      There was no recurrence of the tumor three years after surgery, and function was
      excellent.

PMID- 8131340
TI  - Inflammatory cells in the pseudocapsule of osteosarcoma. A clinicopathologic
      analysis.
AB  - The presence of a "pseudocapsule," composed of an inner compression zone and
      outer reactive zone, is a frequent finding in the periphery of osteosarcoma.
      Morphologic and immunohistochemical methods were used to determine the type of
      inflammatory cell most closely related to the formation of this pseudocapsule.
      Six and five specimens with and without a compression zone, respectively, were
      obtained from ten patients with osteosarcoma. The type and number of inflammatory
      cells in the specimens with and without a compression zone were counted and
      compared. The reactive zone contained mast cells, macrophages, fibroblasts, and
      lymphocytes with a predominance of T-cells. Macrophages were significantly
      increased in number in the specimens with a compression zone. These results
      strongly suggest that macrophages play a significant role in the formation of the
      compression zone. The survival rate of the patients with thick encapsulation was
      markedly better than that of the patients without this feature.

PMID- 8131341
TI  - Surface-based hemangiomas of bone. A review of 11 cases.
AB  - The surface-based hemangioma of bone is an uncommon cause of periosteal- or
      cortical-based lesions. The files of the Armed Forces Institute of Pathology were
      searched for lesions diagnosed as cortical hemangioma or periosteal hemangioma
      received between the years 1950 and 1990; 11 cases with follow-up results were
      identified. The 11 patients ranged in age from 11 to 31 years of age at the time
      of initial symptoms (average, 21 years; mean, 23 years). Sixty percent of the
      patients were male and 40% were female. Skeletal sites of involvement included
      the tibia (45%), the fibula (36%), the femur (9%), and the ulna (9%). Seventy
      percent of patients complained initially of pain (duration, two months to five
      years), whereas 30% reported pain and a mass at the time of initial diagnosis
      (duration, six months to two years). On plain film radiographs, eight lesions
      showed localized cortical thickening, two showed cortical erosion, and one had a
      permeative/destructive pattern. Bone scans showed solitary lesions with increased
      uptake in all 11 patients. The range of histologic types of cortical hemangioma
      included cavernous (six cases), arteriovenous (three cases), venous (one case),
      and pyogenic granuloma type (one case). Clinically, the majority of cases were
      diagnosed as osteoid osteomas; primary pathologic diagnoses included hemangioma
      (27%) and cortical sclerosis (18%). Persistent complaints were reported in three
      patients after intralesional biopsy; no recurrences were reported after en bloc
      excision.

PMID- 8131342
TI  - Anterior decompression for late pain and paralysis after fractures of the
      thoracolumbar spine.
AB  - Anterior decompression of the thoracic and lumbar spine is indicated for patients
      with trauma, infection, or tumor that causes compression of the neural tissues,
      resulting in an incomplete neurologic deficit. The complication of chronic pain,
      with or without paralysis, that results from fractures with canal compromise has
      received little attention. This study involved 45 patients who had anterior
      decompression for chronic pain or paralysis at an average of 4.5 years after
      having thoracolumbar fractures. Pain was improved in 41 of 45 patients, with
      complete relief in 30 and partial relief in 11. In 25 patients with neurologic
      deficit, 21 noted improvement, 14 of which improved one or more grades of the
      Eismont classification. No patient had an increase in pain or loss of neurologic
      function. Complications were few. Anterior decompression of the thoracolumbar
      spine for chronic pain after thoracolumbar fractures is a safe and effective
      treatment for patients with this uncommon and difficult problem.

PMID- 8131343
TI  - Alfacalcidol (alpha D3) and calcium in osteoporosis.
AB  - In a prospective, randomized study, 66 osteoporotic postmenopausal women (mean
      age, 67 years) were scheduled to receive either alfacalcidol 0.25 microgram twice
      daily together with calcium 500 mg twice daily (treatment group, n = 24) or
      placebo twice daily with calcium 500 mg twice daily (control group, n = 42) for
      three years. In the treatment group, bone mineral content at the distal radius
      may have increased by 2% compared to a significant decrease of 7.8% in the
      control group. The difference between the two groups was also significant. Since
      the dose of alfacalcidol and calcium remained unadjusted, frequent
      hypercalciuria, as well as occasional mild, transient elevations of serum
      calcium, were observed in the treatment group. No changes in serum creatinine
      levels or creatinine clearance throughout the study were observed. The two groups
      did not differ with respect to the frequency of clinical side effects, which were
      mainly gastrointestinal and probably related to the calcium supplementation.
      Alfacalcidol and calcium may prevent further bone loss in women suffering from
      postmenopausal osteoporosis.

PMID- 8131344
TI  - Evaluation of limb compartment with suspected increased interstitial pressure. A
      noninvasive method for determining quantitative hardness.
AB  - Six compartments in four dogs and three compartments in three anatomic specimen
      limbs were injected with plasma, and the intracompartmental interstitial pressure
      and hardness of the compartments were measured. Six patients suspected of having
      compartment syndromes were also studied. Of the compartments evaluated in the dog
      and anatomic specimen limbs, the average correlation coefficient between
      measurements with the two methods was 0.95 (range, 0.87 to 0.99). In six patients
      suspected of having compartment syndromes, the ratios of quantitative hardness of
      the injured to uninjured limbs closely matched the intracompartmental
      interstitial pressure measurement ratios (correlation coefficient, 0.95). All
      correlation coefficients were significant (F test, p < 0.05). There was a close
      correlation between the direct measurement of intracompartmental interstitial
      pressure with the wick catheter and quantitative hardness in compartment syndrome
      models in dog and anatomic specimen limbs, and in patients suspected of having
      compartment syndromes. The determination of surface hardness of limb
      compartments, which appears accurate and reproducible, offers the advantages of
      being noninvasive and well suited for longer-term assessments of
      intracompartmental interstitial pressure.

PMID- 8131345
TI  - Growth and metabolism of cultured bone cells using microcarrier and monolayer
      techniques.
AB  - The traditional in vitro cell culture methods provide bone cells on matrix-coated
      Petri dishes to grow the cells in a monolayer. This limits the usefulness in
      situations where there is a need to suspend anchorage dependent cells. To promote
      the massive production of the cultured cells and to enable the suspension of the
      cells in a medium, microcarrier cell culture was developed and evaluated.
      Isolated bone cells from rat calvaria were incubated in a microcarrier culture
      flask with Cytodex 1. The microcarrier cell morphology was examined by a phase
      contrast microscope, a scanning electron microscope, and a transmission electron
      microscope. Cell growth, enzyme markers, and biosynthetic characteristics were
      examined and compared for microcarrier and monolayer methods. The results
      indicate that all the characteristics of the bone cells, whether cultured in the
      Petri dish or microcarrier, were the same. Therefore, the studies of the function
      and behavior of bone cells still remain useful using the microcarrier system
      culture.

PMID- 8131346
TI  - Sensitivity and negative predictive value of swab cultures in musculoskeletal
      allograft procurement.
AB  - Seventy-five fibular specimens were obtained from postmortem donors using aseptic
      surgical techniques. All specimens were swabbed following the same technique as
      routinely used for retrieved musculoskeletal grafts. After swabbing, the
      specimens were placed in BHI-culture medium. Three different protocols were
      subsequently followed: (1) culture of the entire bone specimen in BHI-culture
      medium, (2) culture of the swab incubated on blood agar and chocolate plates, and
      (3) culture of the swab in BHI-culture medium. A control group included 20
      sterilized bone specimens that were cultured entirely in BHI-culture medium
      according to Protocol 1. The sensitivity and negative predictive value were found
      to be 10% and 9% in Protocol 2 and 13% in Protocol 3. These findings imply that
      swab cultures are inadequate to detect bacterial contamination of musculoskeletal
      allografts in all cases. However, the instances of infection after
      transplantation of allografts bacteriologically screened according to Protocols 1
      and 2 do not exceed those reported in other similar series. This suggests an
      acceptable bioburden.

PMID- 8131347
TI  - Healing of large surgical defects of the epiphysial plate. An experimental study.
AB  - In this experimental study using 37 rabbits, the growth and the regeneration
      potential of the distal femoral epiphysial plate were studied by creating a large
      surgical defect in the central part of the plate and filling it with a free fat
      graft. The results evaluated by radiography and histology show that fat grafting
      makes it possible to restore the main part of the longitudinal growth of the bone
      compared with a normal bone (p < 0.01) or the bone injured but left without fat
      grafting (p < 0.001). Regeneration of the growth plate was demonstrated
      histologically and in radiographs. Parts of the epiphysial cartilage continue the
      growth symmetrically without deforming the joint contours. The results of this
      study suggest that in clinical situations it is possible to restore at least part
      of the longitudinal growth of the bone and prevent joint deformity by bridge
      resection even in cases of extensive epiphysial injuries.

PMID- 8131348
TI  - Transfilter bone induction by Chinese hamster ovary (CHO) cells transfected by
      DNA encoding bone morphogenetic protein-4.
AB  - This study was undertaken to identify the factor responsible for classical
      transfilter bone induction by a murine osteosarcoma. Chinese hamster ovary (CHO)
      cells were transfected with the complementary DNA (cDNA) for bone morphogenetic
      protein-4 (BMP-4) that was purified from a murine (Dunn) osteosarcoma. Diffusion
      chambers were filled with the cells expressing the gene for BMP-4 and implanted
      subcutaneously into the flanks of ICR strain nude mice. Ectopic transfilter bone
      formation was seen consistently on the outer surfaces of the cellulose acetate
      membranes of chambers containing transfected cells at three weeks after
      implantation. Bone was not observed on chambers loaded with nontransfected CHO
      cells. The transfected CHO cells were inoculated into nude mice to form tumors,
      which were then homogenized, defatted, and bioassayed also in the ICR, nu/nu
      mice. The cell-free implants consistently elicited new bone and marrow within
      three weeks, whereas the control implants consisting of nontransfected tumor were
      not osteoinductive. These experimental results suggest that BMP-4 is one of the
      molecules responsible for the transfilter bone induction by vital Dunn
      osteosarcoma cells reported by Heiple and for the ectopic bone induction after
      implantation of devitalized, freeze-dried Dunn osteosarcoma tissue described
      originally by Amitani.

PMID- 8131349
TI  - Periosteal and intratumorous bone formation in athymic nude mice by Chinese
      hamster ovary tumors expressing murine bone morphogenetic protein-4.
AB  - Chinese hamster ovary (CHO) cells were transfected with the complementary DNA
      (cDNA) for bone morphogenetic protein-4 (BMP-4) that was derived from the poly A
      RNA of a murine (Dunn) osteosarcoma. A clonal line of the transfected, BMP-4 gene
      expressing cells was expanded and inoculated into the hindlimbs of nude mice to
      produce BMP-4 secreting tumors. The aims of this study were to investigate the
      systemic effects of endogenous BMP-4 production on skeletal growth and radiologic
      density, the local effects of BMP-4 on bone at the tumor-bone interface, and the
      changes in tumor histology as a result of transfecting CHO cells with the gene
      for BMP-4. In control mice, mock vector-transfected CHO cells were inoculated in
      the same manner. Three weeks after the mice received the transfected cells,
      neither enhanced skeletal growth nor a change in bone density was noted. However,
      at the site where the bone was in contact with the tumor, new cartilage and bone
      were consistently observed. The murine BMP-4 transfected CHO tumor contained
      spicules of new bone that have been described as a histologic feature
      characteristic of osteosarcoma.

PMID- 8131350
TI  - Interference fixation versus postfixation of bone-patellar tendon-bone grafts for
      anterior cruciate ligament reconstruction. A biomechanical comparative study in
      porcine knees.
AB  - This study compares biomechanical characteristics of interference screw fixation
      to "postfixation" (sutures tied over cancellous screw and washer) of bone
      patellar tendon-bone grafts in porcine anatomic specimen knees. Maximum pull-out
      strength (ultimate failure load), displacement of the bone graft at 110 N of
      force, and mode of failure were compared in a progressive load to failure test.
      Interference screw fixation demonstrated statistically significantly (p = 0.04)
      higher mean ultimate failure loads (535 N) compared to postfixation (309.1 N).
      Interference fixation also demonstrated statistically significantly (p = 0.0003)
      less displacement of the bone graft at 110 N of force (0.32 mm vs. 2.21 mm). All
      failures occurred at the fixation site. The authors conclude that interference
      fixation is stronger than postfixation and, in the immediate postoperative
      period, should better protect the graft from loosening after anterior cruciate
      ligament reconstruction, improving stability and allowing more aggressive
      rehabilitation.

PMID- 8131351
TI  - Biologic resurfacing of a major joint defect with cryopreserved allogeneic
      periosteum under the influence of continuous passive motion in a rabbit model.
AB  - Periosteal autografts have been widely used for biologic resurfacing of full
      thickness articular cartilage defects in rabbits. This study examined the effect
      of donor and recipient age on biologic joint resurfacing using fresh and
      cryopreserved periosteal allografts in a rabbit model. The study also assessed
      the ability of cryopreserved periosteal allografts to undergo neochondrogenesis.
      Eighty New Zealand rabbits were divided into six groups receiving combinations of
      fresh or cryopreserved allografts. After all the grafts were secured with fibrin
      glue, the animals were subjected to two weeks of continuous passive motion
      followed by four weeks of cage activity or intermittent active motion. The rabbit
      knees were analyzed at six weeks by gross examination, histochemical staining,
      and collagen typing. No significant difference in chondrogenic potential between
      fresh and cryopreserved periosteal allografts was observed. Grafts obtained from
      adult donors were much less chondrogenic than those from adolescents, but adults
      recipients experienced reasonably good results when they received allografts from
      young donors. No evidence of rejection was found in any of the samples as late as
      six weeks after transplantation.

PMID- 8131352
TI  - The role of adhesion molecules in synovial pannus formation in rheumatoid
      arthritis.
AB  - To elucidate the mechanism of cell binding to cartilage, using an
      immunoperoxidase technique with monoclonal antibodies against adhesion molecules,
      the pattern of distribution of these molecules at the rheumatoid pannus-cartilage
      junction has been investigated. Treatment with purified anti-human-monoclonal
      antibody CD54 anti-(ICAM-1) resulted in membrane staining of most of the large
      cells infiltrating the synovial tissue and bordering the pannus cartilage
      junction. When the specimen was treated with purified anti-human-monoclonal
      antibody CDw49d anti-(VLA-4), purified anti-human-monoclonal antibody CDw49e anti
      (VLA-5), most of the cells in the cartilage pannus junction stained, but there
      were few staining cells against purified anti-human-monoclonal antibody CD11a
      anti-(LFA-1). There were some anti-ICAM-1 and anti-VLA-5 staining of the
      chondrocytes at or close to the junction. Human umbilical vein ECBBA1 (ELAM-1)
      staining was only observed on the endothelial cells of postcapillary venules in
      the synovial tissue. These results show that the specific adhesion molecules
      tested may play a role in rheumatoid pannus formation and that the increased
      expression of VLA-4, VLA-5, and ICAM-1 at the cartilage pannus junction may
      represent interaction with matrix protein. The VLA interaction appear to be
      involved in pannus attachment, whereas LFA-1 and ICAM-1 are involved in cell-cell
      interaction and may upregulate molecules such as VLA that are involved in
      attachment.

PMID- 8131353
TI  - Anterior lumbar fusion. A comparison of noncompensation patients with
      compensation patients.
AB  - One hundred fifty-one patients had an anterior interbody lumbar spinal fusion for
      intractable back pain. A solid bony fusion was obtained in 76% of the patients.
      Of patients unemployed before surgery, 50% had returned to work at review. Sixty
      eight percent of patients rated themselves as significantly improved by the
      procedure. Posterior distraction instrumentation neither increased the rate of
      union nor improved the final results. Compensation status and psychological
      disturbance at presentation were significant prognostic factors. Psychological
      disturbance at review had a profound effect on the outcome and patient
      satisfaction ratings. It is recommended that in future studies compensation
      status and psychological disturbances are explicitly included in the outcome
      statistics.

PMID- 8131354
TI  - Anterior surgery in scoliosis.
AB  - Anterior approaches for scoliosis are now frequent. Versatility in exposure is
      such that any segment may be approached from either side without significant
      difficulty or morbidity. Anterior spine surgery is an addition to the modern
      armamentarium by improving correction, insuring fusions, and allowing better
      alignment of the scoliotic spine. In the 1990s, scoliosis patients are
      beneficiaries of innovators of safe and sound anterior spine surgical practice.

PMID- 8131355
TI  - Anterior lumbar fusion options. Technique and graft materials.
AB  - The biomechanical requirements of the ideal lumbar interbody fusion are important
      in the surgical treatment of the vertebral endplates and graft selection. A
      series of 45 patients with anterior lumbar fusion were reviewed retrospectively.
      The fusion was performed with a composite construct consisting of femoral
      allograft cross-sections and allograft cancellous bone. Preparation of vertebral
      endplates consisted of scraping the endplate until punctate bleeding appeared.
      The major part of the endplate was preserved to withstand interspace distraction
      and stability. A 97% fusion rate was achieved based on flexion and extension
      analysis with a six- to 12-month follow-up period. A final average interspace
      distraction of 2.39 mm was reported. The graft should consist of a rigid
      structure that exceeds physiologic loads anticipated in the postoperative period,
      and the composition to promote arthrodesis. Anterior lumbar fusion with femoral
      allograft is an excellent procedure, but long-term further follow-up studies and
      statistical data are essential.

PMID- 8131356
TI  - Titanium-mesh block replacement of the intervertebral disk.
AB  - A prospective clinical trial was conducted involving patients with prolapsed
      lumbar intervertebral disk proven myelographically, who had anterior diskectomy
      and disk replacement with a titanium-mesh block implant. A pilot study was done
      in 1971 on six patients. In this trial, 28 patients were operated on with
      informed consent. Twenty-three had a minimum of five years' follow-up study.
      There were 14 men and boys, and nine women and girls. The average follow-up
      period was eight years and four months (range, five to 12 years three months).
      The average age at operation was 36 years four months (range, 13-66 years).
      Symptomatic improvement were divided into three groups. Sixteen patients were in
      Group 1, three in Group 2, and three in Group 3. Flexion-extension radiographs
      showed 14 patients with no movement between the vertebral bodies adjacent to the
      operated disk, five with minimal movement, and four with definite movement. At
      the implant-bone interface, no radiolucent zone was seen in 18 patients, and a
      definite radiolucent zone was seen in five. Twenty implants were intact, three
      implants had developed a crack, and three were deformed. There were no
      complications. The titanium-mesh block implant is an effective substitute for
      autogenous bone grafting in interbody fusion.

PMID- 8131357
TI  - Reduction of severe lumbosacral spondylolisthesis. A report of 22 cases with a
      ten-year follow-up period.
AB  - Severe spondylolisthesis produces a kyphos at the lumbosacral junction. Reduction
      can be complicated by injury to the cauda equina. To prevent this, a posterior
      decompression and fusion is carried out before a slow reduction in extension. An
      anterior fusion with internal fixation then locks the reduction. Using these
      principles, a good reduction was achieved in 20 of 22 patients. Only two patients
      suffered a permanent neurologic deficit consisting of slight loss of ankle
      dorsiflexion. Severe spondylolisthesis can be safely reduced by this method.

PMID- 8131358
TI  - Surgical treatment of the symptomatic herniated thoracic disk.
AB  - Symptomatic herniated thoracic disks are rare, for their incidence is calculated
      at about one in 1,000,000 persons per year. Although these are usually associated
      with degenerative disease, there are a number of other conditions in which
      thoracic disk herniation is now recognized as being an uncommon but important
      feature. Increased use of noninvasive scanning techniques, together with greater
      clinical awareness, is likely to disclose more cases of herniated disks. Surgical
      treatment of these herniated disks has undergone extensive modification during
      the past 50 years. Microsurgical approaches applied to the spine are major
      contributors to reduced neurologic morbidity. The authors prefer to use the
      transthoracic approach for surgery. High, low, and far lateral approaches are
      also discussed, however, as are other surgical approaches used in the mid to low
      region. Treatment of this difficult diagnostic and management problem is ideally
      managed by a team of medical professionals which includes highly specialized
      surgeons.

PMID- 8131359
TI  - The role of anterior surgery for vertebral fractures with and without cord
      compression.
AB  - The indications for anterior surgery are well defined in the upper and lower
      cervical spine if one accepts the importance of early restoration of stability
      for improved patient rehabilitation. Cannulated screw fixation of Type II
      fractures of the odontoid peg is a highly specialized procedure that requires
      technical expertise still only available at a limited number of orthopaedic
      centers. The engineering improvements in internal fixation for the anterior
      cervical spine, allied with an increasing expertise in instrumentation, have
      increased the tendency toward anterior stabilization for all unstable lower
      cervical fractures, except irreducible dislocations, irrespective of the
      mechanism of injury. Most thoracolumbar fractures with less than 50% to 60% canal
      compromise can be adequately dealt with by posterior surgery, largely because of
      the powerful correction inherent in the short segment, pedicle crew systems
      available. Anterior surgery continues to have a role in the correction of severe
      disruption, late deformity, and chronic anterior cord compression. No ideal
      anterior internal fixation system exists, but the Kaneda device is undoubtedly
      the strongest. The timing and indications for intervention for acute cord
      compression remain controversial in the absence of neurologic deterioration,
      although the route is undisputedly anterior in view of the usual site of
      compression.

PMID- 8131360
TI  - Interbody fusion and instrumentation.
AB  - Fusion indications in adult degenerative disk disease of the lumbosacral spine
      include isolated disk resorption, primary and secondary instability, recurrent
      disk herniation, and pseudarthrosis. Common to these indications are variable
      proportions of biomechanical insufficiency of the motion segment, instability,
      deformity, and spinal stenosis. Apart from favorable psychosocial and work
      related variables, satisfactory outcome is dependent on treatment by a
      combination of diskectomy, decompression, and deformity correction, in addition
      to fusion. Isolated intertransverse or interbody fusions show variable fusion
      rates that are increased by concurrent instrumentation. Persistent pseudarthrosis
      rates and instrumentation failures have prompted circumferential fusion
      techniques. Posterior lumbar interbody fusion (PLIF) and segmental pedicle-based
      plate fixation overcome earlier problems with PLIF by allowing for wide
      decompression and increased exposure for disk space preparation, minimizing
      neural injury. Pedicle fixation restores segmental stability and minimizes graft
      retropulsion. Restoration of anterior column support prolongs instrumentation
      life, and increases fusion rates irrespective of the number of levels fused. Disk
      space distraction, with the use of instrumentation as a working tool, permits
      safer decompression of the intraforaminal zone, a common area of stenosis, and
      single or multilevel deformity correction to restore coronal, axial, and sagittal
      alignment and spinal balance. Even though the surgical technique is demanding,
      fusion rates up to 96% and clinical success up to 86% are achieved.

PMID- 8131361
TI  - Surface tension properties of surfactant.
AB  - Surface tension area relations from pulmonary surfactants (natural, lipid
      extract, synthetic) are obtained with a leak-free captive bubble of controllable
      size. One of the most sensitive parameters to consider is the area change
      required to achieve minimum surface tension. For synthetic surfactant, this
      change can be minimized by increasing the cycling speed of the films. Film area
      reduction at minimum surface tension causes collapse and decreased surface
      activity for all surfactants investigated. To avoid film collapse, positive end
      expiratory pressure becomes important during surfactant replacement therapy.

PMID- 8131362
TI  - Surfactant metabolism.
AB  - Alveolar surfactant pool sizes are small in the preterm animal with RDS, and
      these pool sizes probably increase to approximate those found in preterm animal
      without RDS by 3 to 4 days after birth. De novo synthesis and secretion of
      surfactant phospholipids are slow processes. Therefore, surfactant treatments are
      the only way to acutely increase the pool size. Surfactant phospholipids are very
      slowly catabolized in the preterm lung. The surfactant phospholipids used for
      treatment rapidly associate with lung tissue and are processed by recycling
      through lamellar bodies within type II cells. Surfactant proteins already present
      within the preterm lung can associate with the exogenous surfactant. These
      proteins have metabolic pathways quite different from those for the lipids.
      Surfactant treatments do not seem to interfere with endogenous metabolic pathways
      for surfactant synthesis and secretion. Surfactant treatments of infants with RDS
      are beneficial in part because of the favorable metabolism characterized by a
      preterm lung that can recycle surfactant and does not catabolize the exogenous
      surfactant.

PMID- 8131363
TI  - Metabolism of synthetic surfactants.
AB  - This article provided a brief overview of synthetic surfactants and DPPC
      metabolism, and summarized disposition data on the most widely used synthetic
      surfactant, CPHT (colfosceril palmitate, hexadecanol, and tyloxapol; Exosurf
      Neonatal, Burroughs Wellcome Co.). In separate experiments, young male rabbits
      were given intratracheal administrations of CPHT trace-labeled with either
      hexadecanol-3-[14C], choline-labeled [14C]DPPC, or [3H]tyloxapol. In mass balance
      and tissue distribution studies, radioactivity was quantitated in excreta and
      selected tissues over 5 days. Hexadecanol entered the pathways of intermediary
      lipid metabolism, via oxidation to palmitic acid, which was then utilized in the
      synthesis of phospholipids. After 5 days, most of the radiolabeled dose (56%) was
      distributed throughout the body, with renal (4%) and fecal (2%) excretion being
      minor routes of elimination compared with expired air (28%). The active
      component, DPPC, was still retained by the body (72%) after 5 days, having
      entered the pathways of lipid metabolism to become tissue associated. At this
      time, the lung and liver each contained approximately 10% of the labeled dose,
      whereas elimination in excreta (8%) was minimal compared with that in expired air
      (17%). Tyloxapol and metabolites were retained by the lung, released slowly (t1/2
      = 5 to 6 days) into the systemic circulation, and eliminated through fecal (27%)
      and renal (26%) excretion.

PMID- 8131364
TI  - Clinical trials of natural surfactant extract in respiratory distress syndrome.
AB  - Since the first use of natural surfactant extract by Fujiwara to treat premature
      infants with respiratory distress syndrome (RDS), multiple randomized controlled
      clinical trials involving more than 2500 infants have been reported. These trials
      have used prophylactic administration of surfactant to high-risk premature
      infants (prevention trials) or administration of surfactant to premature infants
      with moderate to severe RDS (rescue or treatment trials). This article shows meta
      analysis of the trial data, significant effects of natural surfactant extracts,
      and significant clinical benefits.

PMID- 8131365
TI  - Clinical trials of synthetic surfactant in the respiratory distress syndrome of
      premature infants.
AB  - This article outlines the controlled clinical trials that have been performed
      with synthetic surfactant preparations in the management of premature newborn
      infants. The results have shown impressive reductions of mortality and in the
      incidence of air-leak complications. Complications appear to be few and mild,
      although the occurrence of pulmonary hemorrhage is increased in very small
      infants. The 1- and 2-year follow-up data suggest that there is not an increase
      in the number of impaired surviving children.

PMID- 8131366
TI  - Other uses of surfactant.
AB  - Surfactant is found not only in the alveoli but in bronchioles and small airways.
      Along with its important role in surface-tension reduction in alveoli, surfactant
      has several other properties. Any condition characterized by mucus abnormality,
      mucociliary transport deficiency, airway obstruction, or bronchoalveolar collapse
      could potentially benefit from exogenous surfactant therapy. Anti-inflammatory
      and bactericidal properties of surfactant could provide additional benefit in a
      variety of diseases.

PMID- 8131367
TI  - Genetically engineered human pulmonary surfactant.
AB  - Pulmonary surfactant is a complex array of phospholipids and proteins that
      specifically interact to lower the surface tension in the alveoli of the lungs.
      This article reviews pulmonary surfactant proteins A, B, and C. Also surfactant
      replacement in animal studies is discussed.

PMID- 8131369
TI  - Medicine's most recent challenge--AHPs.

PMID- 8131368
TI  - Designer surfactants. The next generation in surfactant replacement.
AB  - Exogenous surfactant replacement mixtures currently used for the prevention and
      treatment of neonatal respiratory distress syndrome are either obtained from
      mammalian lungs or are totally synthetic. The synthetic surfactants contain no
      surfactant proteins and tend to show less surface activity than protein
      containing mammalian-based surfactants. However, these preparations are more
      easily prepared and carry less antigenic risk. The next generation of exogenous
      surfactant promises to be a synthetic lipid mixture that contains recombinant
      proteins or synthetic peptides. Such mixtures should minimally demonstrate the
      surface activity and resistance to inhibitory factors displayed by the natural
      surfactants but have the advantages of synthetic preparations.

PMID- 8131370
TI  - Competition and the changing role of medical societies. 1984.

PMID- 8131371
TI  - Parental leave policies.

PMID- 8131372
TI  - ColoradoCare.

PMID- 8131373
TI  - MRSA protocol for long term care facilities.

PMID- 8131374
TI  - More HIV info.

PMID- 8131375
TI  - Ampliative inference: on choosing a probability distribution.
AB  - Ampliative inference is the choice of a probability distribution on the basis of
      incomplete information. We consider some psychological and normative questions
      that arise about this kind of reasoning. The discussion is largely tutorial
      although a substantive hypothesis is also advanced.

PMID- 8131376
TI  - Spatial attention and two modes of visual consciousness.
AB  - The relationship between spatial attention and visual consciousness was
      critically examined in an attempt to show the operation of two simultaneously
      available modes of visual consciousness (i.e., object consciousness, which
      concerns the conscious identification of objects, and background consciousness,
      which deals with conscious monitoring of the background scene). The traditional
      view seems to pay attention only to object consciousness, which is a product of
      spatial attention. To substantiate the hypothesis, five topics from varied fields
      of human experimental psychology were chosen: iconic storage, stabilized retinal
      image disappearance, stable perception of external space, texture segregation and
      attention, and spatial frequency sensitivity in a figure-ground reversal figure.
      The findings of these studies suggest that there may be visual consciousness
      outside of focal attention and that background consciousness operates as a
      default mode for global scene analysis and early warning of anomalies. Finally,
      neural substrata for these two modes of consciousness are suggested.

PMID- 8131377
TI  - Answering the connectionist challenge: a symbolic model of learning the past
      tenses of English verbs.
AB  - Supporters of eliminative connectionism have argued for a pattern association
      based explanation of language learning and language processing. They deny that
      explicit rules and symbolic representations play any role in language processing
      and cognition in general. Their argument is based to a large extent on two
      artificial neural network (ANN) models that are claimed to be able to learn the
      past tenses of English verbs (Rumelhart & McClelland, 1986, Parallel distributed
      processing, Vol. 2, Cambridge, MA: MIT Press; MacWhinney & Leinbach, 1991,
      Cognition, 40, 121-157). In this article we critically review Rumelhart and
      McClelland's as well as MacWhinney and Leinbach's ANN models and conclude that
      they do not succeed in the assigned task of learning the past tenses of English
      verbs. In order to answer their challenge to the symbolic processing approach, we
      present our symbolic pattern associator (SPA)-a general-purpose pattern
      associator that can learn to associate arbitrary discrete patterns. We carried
      out several experiments with the SPA using the same set of verbs that was used in
      MacWhinney and Leinbach's simulation with more realistic training and testing
      procedures. The SPA outperformed the connectionist models by a wide margin in the
      accuracy of learning, and successful inductive generalizations to unseen verbs.
      Our SPA has very natural and psychologically realistic explanations to many
      psychological effects such as U-shaped learning curve, and is much closer to
      human subjects in predicting past tense of the pseudo-verbs. In contrast to ANNs,
      whose internal representations are entirely opaque, the SPA can represent the
      acquired knowledge in the form of production rules that allow for further higher
      level processing and integration, resulting in linguistically realistic
      associative templates for irregular verbs and production rules for regular verbs.
      In the light of these findings, we conclude that eliminative connectionists'
      vision of cognition as simple pattern association and pattern recognition without
      symbolic representation is inadequate. Pattern association as such does not imply
      rule-less or cue-based models of language acquisition or of human learning in
      general.

PMID- 8131378
TI  - The representation of location in visual images.
AB  - By definition, visual image representations are organized around spatial
      properties. However, we know very little about how these representations use
      information about location, one of the most important spatial properties. Three
      experiments explored how location information is incorporated into image
      representations. All of these experiments used a mental rotation task in which
      the location of the stimulus varied from trial to trial. If images are location
      specific, these changes should affect the way images are used. The effects from
      image representations were separated from those of general spatial attention
      mechanisms by comparing performance with and without advance knowledge of the
      stimulus shape. With shape information, subjects could use an image as a
      template, and they recognized the stimulus more quickly when it was at the same
      location as the image. Experiment 1 demonstrated that subjects were able to use
      visual image representations effectively without knowing where the stimulus would
      appear, but left open the possibility that image location must be adjusted before
      use. In Experiment 2, distance between the stimulus location and the image
      location was varied systematically, and response time increased with distance.
      Therefore image representations appear to be location-specific, though the
      represented location can be adjusted easily. In Experiment 3, a saccade was
      introduced between the image cue and the test stimulus, in order to test whether
      subjects responded more quickly when the test stimulus appeared at the same
      retinotopic location or same spatiotopic location as the cue. The results suggest
      that location is coded retinotopically in image representations. This finding has
      implications not only for visual imagery but also for visual processing in
      general, because it suggests that there is no spatiotopic transform in the early
      stages of visual processing.

PMID- 8131379
TI  - Beyond visible persistence: an alternative account of temporal integration and
      segregation in visual processing.
AB  - When processing sequences of rapidly varying stimuli, the visual system must
      satisfy two conflicting requirements. To maintain perceptual continuity,
      sequential stimuli must be integrated into a single, unified percept. On the
      other hand, to detect rapid changes, sequential stimuli must be segregated from
      each other. We propose that these conflicting demands are reconciled by a process
      that codes the temporal relationship between contiguous stimuli: Stimuli that are
      coded as co-extensive are integrated and those that are coded as disjoint are
      segregated. This approach represents a conceptual departure from the more
      traditional "intrinsic persistence" view of temporal integration. The approach
      provides a parsimonious account of the results of two temporal-integration tasks
      in which the durations of the leading and trailing displays were varied over a
      broad range. The data were accurately fit by a quantitative model in which
      temporal codes were determined by the correlation in time between the visual
      responses to the leading and trailing displays.

PMID- 8131380
TI  - DSM-III and DSM-III-R: what are American psychiatrists using and why?
AB  - The purpose of this study was to determine whether American psychiatrists have
      switched from DSM-III to DSM-III-R as their primary diagnostic reference, and to
      examine what factors predicted the continued use of DSM-III. In 1989, we
      conducted a mail survey of practicing psychiatrists (N = 454), residency program
      directors (N = 128), residents (N = 1,331), and researchers (N = 196) regarding
      their training in, use of, and opinions about DSM-III and DSM-III-R.
      Approximately 30% of practitioners continued to use DSM-III as their primary
      diagnostic reference, although this was less frequently true of researchers and
      residents. In none of the four groups did a majority believe that DSM-III-R was
      needed, despite the fact that the majority of each group indicated that it was an
      improvement over DSM-III. The most commonly perceived reasons for publishing DSM
      III-R were that it corrected problems with DSM-III and new research indicated
      changes were warranted. Compared with DSM-III-R users, DSM-III users more
      frequently believed that the 7-year interval between the two editions was too
      short, that DSM-III-R was not needed, and that the revised manual was little
      better than the original. Thus, 2 years after the publication of DSM-III-R 90% of
      psychiatrists were using DSM-III-R, at least in part, although a substantial
      minority continued to use DSM-III as their primary diagnostic manual. Even among
      DSM-III-R users, many believed that the revised manual was not needed. The
      perceived need for DSM-III-R was associated with the reasons ascribed to its
      publication; therefore, acceptance of DSM-IV may be partially a function of how
      its development is promoted and justified. That nearly one third of a random
      sample of practicing psychiatrists continued to use DSM-III supports concerns
      that the publication of DSM manuals every 6 or 7 years will divide the
      psychiatric community into subgroups using different diagnostic criteria.

PMID- 8131381
TI  - The use of the DSM-III-R Checklist for initial diagnostic assessments.
AB  - The DSM-III-R Checklist is an efficient method for screening psychiatric patients
      for major psychiatric disorders while amassing a data base that can be used for
      later clinical and research activities. It yields valid diagnoses and key
      adjunctive symptoms. Patients enjoyed the interview, demonstrating an interest in
      the computer as well as a feeling of confidence in the complete review of
      symptoms. The psychiatry resident users in this project found the Checklist to be
      a valuable teaching instrument, a way to develop their thinking about symptoms
      and diagnostic rules, an efficient means of collecting an automated clinical data
      base, and a stimulus to pursue further research activities. Finally, the
      Checklist is an ideal diagnostic tool to amass a research data base and is
      currently being used in numerous studies by clinicians and nonclinicians.

PMID- 8131382
TI  - Empirical determination of thresholds for case identification: validation of the
      Personality Diagnostic Questionnaire-Revised.
AB  - The Personality Diagnostic Questionnaire-Revised (PDQ-R) was sent to first-degree
      relatives of major psychotic patients for identification of DSM-III-R personality
      disorders (PDs). Responses to the PDQ-R were interpreted both literally and
      empirically, and compared with the Structured Interview for DSM-III PDs (SIDP) as
      the standard. For literal interpretation, symptoms reported were counted directly
      for case identification using fixed DSM-III-R thresholds. The empirical approach
      adjusted the threshold for case identification to maximize concordance with the
      SIDP. Comparison of the two methods showed that using empirically determined
      thresholds in some scales gives better concordance with the SIDP. For the
      dependent and histrionic PD scales, the improvements were statistically
      significant. The area under the receiver operating characteristic (ROC) curve was
      computed for each PDQ-R scale to summarize its discriminatory capability across
      all thresholds. Areas under the ROC curve indicated that the schizoid,
      schizotypal, borderline, dependent, passive-aggressive, and histrionic PD scales
      in the PDQ-R have better discriminatory qualities than other PDQ-R scales.

PMID- 8131383
TI  - Terms of madness: historical linguistics.
AB  - The etymological origins of commonly used descriptors of mental conditions are
      explored. In reviewing history for signs of mental disorders, we need to
      understand the terms used previously to indicate abnormalities. A wealth of terms
      is evident indicating that, contrary to the conclusions of some historians,
      mental illnesses have an extended and broad history.

PMID- 8131384
TI  - Clozapine treatment of borderline patients: a preliminary study.
AB  - Clinicians frequently encounter patients who present with borderline personality
      disorder (BPD) and prolonged and/or pronounced psychotic symptoms of an atypical
      nature. Fifteen such patients were treated with clozapine and rerated blind to
      baseline symptomatology and functional level from 2 to 9 months after beginning
      treatment (mean = 4.2 +/- 2.1). The overall symptomatology of these patients as
      rated on the Brief Psychiatric Rating Scale (BPRS) decreased significantly from a
      mean of 57.0 +/- 10.4 to a mean of 37.8 +/- 7.7 (t = 7.03, df = 14, P = .001).
      Their positive, negative, and general symptoms as rated by the BPRS also
      decreased significantly. Additionally, their Global Assessment Scale (GAS) score
      increased significantly from a mean of 30.8 +/- 4.7 to a mean of 43.1 +/- 8.6 (t
      = 5.19, df = 14, P = .001). These results suggest that clozapine may be an
      effective antipsychotic agent for this subset of BPD patients. However, double
      blind, placebo-controlled studies are necessary to confirm these preliminary
      results.

PMID- 8131385
TI  - Anorexia nervosa and "reverse anorexia" among 108 male bodybuilders.
AB  - Two disorders of body image encountered in a study of 108 bodybuilders are
      described. In a study of the psychiatric effects of anabolic steroids, structured
      interviews were administered to 55 bodybuilders who had used anabolic steroids
      and 53 non-user controls. Three (2.8%) of the subjects reported a history of
      anorexia nervosa--a rate far higher than the 0.02% rate typically reported among
      American men (P < .001). Nine (8.3%) of the subjects, two of whom were former
      anorexics, described a "reverse anorexia" syndrome, where they believed that they
      appeared small and weak even though they were actually large and muscular.
      Reverse anorexic subjects reported that they declined social invitations, refused
      to be seen at the beach, or wore heavy clothes even in the heat of summer because
      they feared that they looked too small. All nine reverse anorexia cases occurred
      among steroid users; none occurred among non-users (P < .003). Four subjects
      reported that their reverse anorexic symptoms contributed to their decision to
      start using steroids. Disorders of body image, including both anorexia nervosa
      and its reverse form, may occur frequently in men who lift weights regularly.
      Reverse anorexia may precipitate or perpetuate the use of anabolic steroids in
      some individuals.

PMID- 8131386
TI  - The role of psychological risk factors in recovery from borderline personality
      disorder.
AB  - This study examined the role of psychological risk factors in recovery from
      borderline personality disorder (BPD). A lifetime BPD group (n = 13) was composed
      of female subjects who had met the criteria for BPD in the past but no longer did
      so in the present. The comparison group was a sample with active BPD (n = 26).
      Psychological risk factors were measured by a developmental interview, which
      scored childhood sexual abuse (CSA) and its parameters, childhood physical abuse
      (PA), and separation or loss, as well as by the Parental Bonding Index (PBI).
      Subjects from the active BPD group showed a trend toward higher rates of CSA, and
      had a significantly higher CSA severity score. The results suggest that a history
      of severe CSA may adversely influence recovery from BPD.

PMID- 8131387
TI  - A new identity for misidentification syndromes.
AB  - The systematic study of delusional misidentification syndromes has been hampered
      by the often confusing and imprecise eponymic nomenclature currently in use. We
      present a case report that demonstrates the inadequacies of the current system.
      We then propose a new classification system designed to improve research and
      understanding in this important area.

PMID- 8131388
TI  - Diagnosis and clinical features of borderline personality disorder in the east
      and west: a preliminary report.
AB  - In the first clinical study of the borderline personality disorder (BPD) in Asia,
      the Diagnostic Interview for Borderlines (DIB) was performed on 85 female
      outpatients aged 18 to 30 years in Japan. BPD was diagnosed in 32 (38%) of these
      patients. The International Classification of Diseases-9 (ICD-9) diagnoses made
      at the initial examination of the DIB-identified BPD patients were, in order of
      frequency, neurotic disorders, anorexia nervosa and other eating disorders, and
      manic-depressive psychoses. The DSM-III axis I diagnoses of the DIB-identified
      BPD patients were affective disorders in 63%, eating disorders in 34%, and
      substance use disorders in 22%. This study suggests that there are indeed BPD
      patients in Japan. An exception is made of the low incidence of substance use
      disorders, and of the fact that most Japanese patients continue to maintain
      stormy one-to-one or masochistic relationships with their parents because they
      live at home--their clinical picture is not different from that of American
      patients.

PMID- 8131389
TI  - Selection bias in the study of spouse similarity for psychiatric morbidity in
      clinical samples.
AB  - The existing literature on spouse similarity for health variables can be divided
      into two fields of application, high blood pressure and other coronary risk
      factors and psychiatric morbidity. In the former field, almost all studies have
      been conducted on general-population samples, whereas in the psychiatric field,
      most of the investigations studied clinical samples, i.e., where one or both
      members of the couple were under psychiatric treatment. In this report, we
      demonstrate that studies of spouse similarity for psychiatric morbidity are
      subject to selection bias whenever they are conducted on clinical samples. This
      selection bias has a double origin. First, some bias arises from the fact that
      the probability of a couple being drawn for a clinical sample is dependent on
      whether one or both spouses are afflicted with the illness in question. A second
      source of bias lies in the likelihood that each spouse's help-seeking behavior is
      not independent of the other's. It would appear then that, owing to this
      selection bias, it is preferable to restrict the study of spouse similarity for
      psychiatric morbidity to general-population samples.

PMID- 8131390
TI  - Characterizing organic mood syndrome, depressed type.
AB  - In this report, a first comprehensive description of the clinical features of
      patients with organic mood syndrome, depressed type (OMS-D), in a psychiatric
      hospital population is presented. This description is based on information from
      130 OMS-D patients among 14,889 patients who presented for initial evaluation
      over a 5-year period. This description includes an enumeration of the common
      clinical symptoms of this syndrome. Following this, the severity of the symptoms
      of OMS-D are compared with those of its crude "functional" equivalent of major
      depressive disorder, single episode (MDD-SE). In addition, associated factors are
      presented concerning demographics, level of functioning, comorbidity,
      electroencephalographic and computed tomographic abnormalities, and current
      physical problems. These findings provide preliminary support for the validity of
      this diagnostic category, and provide relevant information concerning proposed
      changes in this category as listed in the DSM-IV Options Book.

PMID- 8131391
TI  - Long-term follow-up of generalized anxiety disorder.
AB  - The diagnostic stability and long-term prognosis of generalized anxiety disorder
      (GAD) remain the subjects of considerable controversy. We report the results of
      an investigation of the long-term outcome of an original sample of 44 subjects
      who participated in a medication trial. Subjects were reinterviewed approximately
      16 months after completion of the study, using structured interviews. Fifty
      percent continued to fulfill criteria for GAD. Other concurrent axis I diagnoses
      were as follows: dysthymia, 11%; major depression, 7%; and social phobia, 7%.
      Regarding axis II comorbidity, subjects with chronic GAD were more likely to
      fulfill criteria for one or more personality disorders, especially in clusters B
      and C. In addition, follow-up subjects with GAD and with remitted GAD reported a
      statistically equivalent number of recent life events, although subjects with
      chronic GAD were more likely to report significant dissatisfaction with life. The
      findings indicate that although many subjects with GAD do not follow a chronic
      course, many others remain symptomatic. The results also suggest that GAD
      symptoms are not simply the result of a subject's recent negative experiences,
      and that life satisfaction measures are an accurate reflection of GAD outcome.

PMID- 8131392
TI  - A systematic assessment of the comorbidity of DSM-III-R personality disorders in
      alcoholic outpatients.
AB  - To our knowledge, this is the first study to examine the systematic comorbidity
      of DSM-III-R personality disorders (PDs) in a sample of alcoholic outpatients.
      The extent and direction of overlap can provide a measure of heterogeneity and
      descriptive validity. Fifty sober alcoholic outpatients enrolled in a treatment
      program were assessed by Structured Clinical Interview for DSM-III (SCID)
      instruments for the presence of axis I and axis II disorders; 80% had either a
      coexistent axis I or II disorder, with 66% having an axis I disorder, 64% an axis
      II disorder, and 50% both axis I and II disorders. There were 84 PD diagnoses
      among the 32 PD patients (2.6/patient), with multiple diagnoses in 20 (62%). The
      most prevalent PD diagnoses were paranoid (44%), antisocial (20%), avoidant
      (20%), passive-aggressive (18%), and borderline (16%). Overlap was extensive and
      not confined to any one of the three designated axis II clusters. Poorer outcome
      was associated with the presence of PD. Personality variables may offer a means
      of further characterizing the heterogeneity observed in axis I disorders. Further
      refinement of the current system of PD classification and investigation into
      alternate models is needed.

PMID- 8131393
TI  - Methotrexate for abortion at < or = 42 days gestation.
AB  - Methotrexate is cytotoxic to trophoblast and, in low doses, has minimal side
      effects. It is used to treat gestational trophoblastic neoplasia and ectopic
      pregnancy and has recently been shown to have similar effects on intrauterine
      trophoblast. A prior study suggested that methotrexate may successfully cause
      abortion of an early pregnancy without prostaglandin. To test this hypothesis,
      ten pregnant women at < or = 42 days gestation were treated with methotrexate 50
      mg/m2 intramuscularly. Vaginal bleeding started 24 +/- 10 (mean +/- standard
      deviation) days after the injection and lasted 10 +/- 3 days. Methotrexate side
      effects occurred in 4 patients and were limited to the first 4 days after the
      injection. Methotrexate alone appears sufficient to abort a very early
      intrauterine pregnancy.

PMID- 8131394
TI  - THe "U" technique: a new method for Norplant implants removal.
AB  - The standard technique for Norplant implants removal was compared with a new
      technique called the "U" technique, which employs the use of a modified no
      scalpel vas deferens holding forceps to grasp and remove the capsules. Seventy
      six women requesting Norplant implants removal were randomly assigned to Group 1
      (standard removal technique) or Group 2 ("U" removal technique). Variables
      measured included: (a) time required for complete removal, (b) number of capsules
      not broken or damaged during removal, and (c) number of incisions required for
      removal of all six capsules. In clients with visible or palpable capsules, the
      standard removal technique required significantly more time to remove all six
      capsules, on average, than the "U" technique (19 versus 7 minutes, p < 0.001);
      also more capsules were damaged during removal (5.6 undamaged versus 6.0, p <
      0.01). In addition, with the standard technique, five clients required two
      incisions for removal of all six capsules while none of the clients required more
      than one incision with the "U" technique. Our conclusion is that the "U"
      technique is a quicker and easier method of removing Norplant capsules than the
      standard technique.

PMID- 8131395
TI  - Condom breakage during commercial sex in Chiang Mai, Thailand.
AB  - Used condoms in 30 female brothels in Chiang Mai, Thailand, during the period
      from August 1992 to October 1992 were examined for breakage. Data were also
      collected by interviewing 326 prostitutes who accounted for 65 percent of the
      total prostitutes providing condoms. The prostitutes had a mean age of 20.6 +/-
      3.2 years. Sixty-one percent had no formal education. The median duration of
      prostitution was 13 months. The average number of clients per day in the past 24
      hours and in the past 3 months was 4.4 +/- 2.5 and 5.5 +/- 2.2, respectively.
      Eighty-eight percent charged between $2 and less than $8 for their sexual
      service. All refused to practice oral or anal sex during the past 24 hours. Of
      5,559 condoms, 298 were used two at a time and 15 were used three at a time. The
      breakage rate per act of intercourse was 5.9 percent (95% CI = 5.3, 6.5). The
      breakage per total condoms examined was 5.7 percent (95% CI = 5.1, 6.3). Breakage
      relating to manufacturing defect, i.e., pinholes, and that relating to use was
      0.8 percent (95% CI = 0.6, 1.0) and 5.0 percent (95% CI = 4.4, 5.6),
      respectively. The probability of breakage when using two condoms at the same time
      was 3.4 percent (95% CI = 0.5, 6.3). Most of the breakage occurred at the distal
      part of the condom. There was no difference between the breakage rates of condoms
      provided by the brothels and those brought by the client; nor was there any
      difference between manufacturing defect or use. The breakage rate per client as
      estimated by prostitutes in the past 24 hours corroborated with that assessed by
      examination.

PMID- 8131396
TI  - Pharmacokinetics and bioavailability of ST 1435 administered by different routes.
AB  - The ovulation inhibiting potency of the synthetic progestin ST 1435 (Nestorone)
      is high after parenteral administration and practically nil after oral
      administration. The purpose of this study was to determine the pharmacokinetic
      parameters of ST 1435 after single oral or intravenous administration or after
      long-term treatment with subdermal implants in women. After administration, as a
      single i.v. bolus, the plasma disappearance rate of immunoreactive ST 1435 had
      two components with half-lives (mean +/- SE) of 3.5 +/- 0.5 and 83 +/- 14 min,
      respectively. The volume of distribution was 4.7 +/- 1.3 L/Kg and the metabolic
      clearance rate was 55 +/- 6 L/Kg/d. After oral administration, the
      bioavailability was about 10% of the dose. After chronic subdermal
      administration, the plasmatic clearance was slower than following the acute
      doses. These results show that ST 1435 has shorter half-lives and a faster
      clearance rate than progestins which bind SHBG. The large volume of distribution
      indicates accumulation in the extravascular space and was expected in view of the
      high affinity of ST 1435 for progesterone receptors. The slower plasma
      elimination rate after chronic administration was attributed to the re-entry of a
      larger mass of drug from the extravascular space, and/or accumulation of
      immunoreactive metabolites with slower clearance than the parent steroid.

PMID- 8131397
TI  - Pharmacokinetics of cyproterone acetate and ethinylestradiol in 15 women who
      received a combination oral contraceptive during three treatment cycles.
AB  - The pharmacokinetics of cyproterone acetate (CPA) and ethinylestradiol (EE2) were
      determined in 15 healthy women (age 19 to 34 years), following single dose
      administration of a combination oral contraceptive, containing 2.0 mg CPA
      together with 0.035 mg EE2 (Diane-35R). After a wash-out period of one week, the
      same preparation was administered during a treatment period of three months.
      After single dose administration, maximum concentrations of CPA in the serum were
      15.2 +/- 6.6 ng/ml. Post maximum drug levels declined biphasically with half
      lives of 0.8 +/- 0.4 h and 54.0 +/- 26.0 h, respectively. The apparent clearance
      was calculated to be 3.6 +/- 0.9 ml x min-1 x kg-1 and the volume of distribution
      (Vz) was 986 +/- 4371. The free fraction of CPA was 3.5 +/- 1.9% and the
      fractions bound to heat labile proteins and albumin were 4.6 +/- 2.2% and 92.0 +/
      3.5%, respectively. Trough levels of CPA in the serum increased during a
      treatment cycle, reaching a steady-state around day 16. An about two-fold
      accumulation of CPA was observed, which was less than expected theoretically.
      SHBG concentrations in the serum increased by a factor of three during a cycle,
      without having any effect on the protein binding of CPA. At the end of treatment
      cycle three, the terminal half-life of CPA had increased to a mean value of 78.6
      +/- 16.0 h and the volume of distribution to a value of 1304 +/- 427 1. The
      apparent clearance showed a small, although significant decrease to a value of
      3.0 +/- 0.4 ml x min-1 x kg-1. The observed changes Vz and t 1/2 during the
      treatment period were attributed to the distribution of CPA into a deep
      compartment and the slow release of the drug from this compartment. The AUC(0-4h)
      values of EE2 following single dose administration of the combination oral
      contraceptive were found to be 187.5 +/- 79.7 pg x ml-1 x h. On the last day of
      cycles one and three, the AUC(0-4h) values were 311.2 +/- 109.3 and 304.8 +/-
      121.5 pg x ml-1 x h, respectively, which corresponds to an about 60% increase as
      compared to single dose administration. Total and free testosterone
      concentrations decreased during treatment cycles one and three by about 39% and
      62%, respectively, compared with the corresponding values measured prior to
      treatment.

PMID- 8131398
TI  - Effect of norethisterone acetate on serum lipid and lipoprotein parameters as
      well as on blood coagulation in female monkeys (M. fascicularis).
AB  - The effects of daily oral administration of a high dose of 10 mg norethisterone
      acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters
      as well as on blood coagulation were investigated in female monkeys (M.
      fascicularis). Measurements of lipids and lipoprotein cholesterol were performed
      in weeks--5 and -1 before treatment and in weeks 4, 8 and 12 after treatment. In
      addition, various blood coagulation and fibrinolytic parameters were determined
      in weeks 11-14 after treatment with NET-Ac. Furthermore, the serum levels of
      norethisterone (NET) were determined in order to monitor the real systemic
      compound exposure and revealed that Cmax and AUC (0-3 h) values reached for
      norethisterone in this experiment in monkeys were about 25 times higher than
      those obtained after an oral contraceptive dose of NET-Ac. in women. The results
      of lipid and lipoprotein cholesterol determinations showed decreases in serum
      total lipids, phospholipids, triglycerides and total cholesterol associated with
      similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.
      treatment in monkeys. These effects were observed from week 4 onwards and
      maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL
      cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged.
      Thus, the results obtained in this study after high-dose treatment with NET-Ac.
      in monkeys did not indicate any changes of lipid and lipoprotein parameters which
      in humans are supposed to be associated with an increased risk of cardiovascular
      lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions. The
      results of blood coagulation and fibrinolytic parameters showed increased
      antithrombin-III and plasminogen levels besides minor changes in other
      parameters, thus indicating that NET-Ac.-treatment does not contribute to an
      increased risk of cardiovascular thrombotic events in the cynomolgus monkey.

PMID- 8131399
TI  - Studies on the contraceptive efficacy of Praneem polyherbal cream.
AB  - Praneem polyherbal cream, a spermicidal formulation, has been developed at the
      National Institute of Immunology, which makes use of Praneem, a purified extract
      from the dried seeds of an ancient Indian plant Azadirachta indica (Neem),
      extract from the pericarp of fruits of Sapindus species and quinine
      hydrochloride. These ingredients have a synergistic spermicidal activity and an
      optimised formula was derived. The components were made into a water-soluble
      cream base prepared by using pharmaceutically acceptable base and stabilised by
      addition of IP grade antioxidant and preservatives. The cream is devoid of
      irritation and sensitization potential, as seen with standard Draize test on
      normal and abraded skin of rabbits and by 21-day cumulative skin sensitivity in
      human volunteers. The formulation was found to be safe under subacute toxicity
      studies in monkeys. The formulation has shown high contraceptive efficacy in
      rabbits and in monkeys after intravaginal application. The shelf-life of the
      cream at room temperature is estimated to be 18 months by accelerated stability
      studies.

PMID- 8131400
TI  - The high-risk keratoplasty patient--quo vadis?

PMID- 8131401
TI  - Protection of the iris by lamellar dissection of corneal layers. A technique in
      penetrating keratoplasty.
AB  - Adherent leukomatous corneal opacities constitute the bulk of cases undergoing
      keratoplasty in developing countries. Surgical trauma to the iris resulting in a
      large iris coloboma, iridodialysis, and bleeding are the imminent intraoperative
      complications in such cases. We have evolved a technique of lamellar separation
      of corneal layers and gentle separation of adherent iris after partial
      trephination in such cases. We have successfully used this technique in six cases
      of adherent leukoma. No intra-or postoperative complication related to lamellar
      separation was encountered, and all the grafts remained clear at the end of 3
      months.

PMID- 8131402
TI  - Remodelling of the corneal stroma after lamellar keratoplasty. A synchrotron x
      ray diffraction study.
AB  - Patients healing from lamellar keratorefractive surgeries invariably experience
      postoperative corneal haze. In our lamellar keratoplasty (LKP) rabbit model,
      visual recovery is concomitant with the invasion of the grafted tissue by viable
      keratocytes from adjacent host tissue, and the return of corneal clarity is
      attributed to the remodelling of the stromal tissue by these keratocytes. We used
      synchrotron x-ray diffraction techniques to elucidate the ultrastructure of the
      stromal collagen fibrils in rabbit corneas at various time points in the 3 months
      after LKP surgery. Lenticules were frozen in 50% of the cases. The average
      spacing of the collagen molecules, which constitute the stromal fibrils, remains
      unchanged by LKP in both frozen (1.69-1.73 nm) and nonfrozen (1.58-1.75 nm)
      cases. In the nonfrozen case, the collagen fibril diameters are initially
      slightly larger than normal (38.3-41.9 nm) but have receded by 2 months
      postoperatively [similar to the frozen cases (37.7-41.9 nm)]. The post-LKP
      spacing of the collagen fibrils in the nonfrozen corneas is unremarkable (56.2
      69.2 nm). In contrast, the increased collagen interfibrillar spacing in the
      frozen case is considerable (56.7 to > 94.6 nm) and variable up to 21 days
      postoperatively. Because the changes in interfibrillar spacing did not always
      mirror pachymetry changes in the frozen cases, we suspect occasional graft
      malapposition or the formation of intrastromal, fluid-filled, collagen-free
      "lakes."

PMID- 8131403
TI  - Suppression of graft rejection using 15-deoxyspergualin in the allogeneic rat
      penetrating keratoplasty model.
AB  - We tested the ability of 15-deoxyspergualin (DSG), a new immunosuppressant, to
      inhibit corneal allograft rejection in the rat penetrating keratoplasty model.
      Fifty-six inbred Lewis rats were recipients of orthotopic corneal allografts from
      Brown Norway rats. Allogeneic groups received daily intramuscular injections of
      DSG 2, 3, 4, or 10 mg/kg/day. The animals treated with 2 mg/kg/day had four out
      of 10 grafts rejected; in the 3 mg/kg/day group none of the six grafts rejected;
      whereas in the 4 mg/kg/day group one out of 15 grafts rejected. The animals
      treated with 10 mg/kg/day became emaciated and died during the second and third
      postoperative weeks with relatively clear grafts. All corneas rejected following
      discontinuation of the drug. We conclude that the systemic administration of DSG
      at 3 or 4 mg/kg/day results in effective suppression of corneal allograft
      rejection in the rat penetrating keratoplasty model.

PMID- 8131404
TI  - Corneal disorders in floppy eyelid syndrome.
AB  - The corneal findings in 60 patients with floppy eyelid syndrome seen at the
      Bascom Palmer Eye Institute over a 10-year period were determined by review of
      their medical records. Punctate epithelial keratopathy (45%), and both clinical
      (10%) and subclinical keratoconus were the most commonly encountered corneal
      disorders. Two patients developed progressive endotheliopathy (Chandler's
      syndrome and nonguttate endothelial dystrophy) during the period of observation.
      In contrast to previous reports in which almost all patients were obese men, 37%
      (n = 22) of our patients were women and only 29% of all patients were obese. All
      patients slept face down, usually on the most severely affected eye. Treatment by
      lid shortening surgery and/or an eye shield provided symptomatic relief. A
      pathogenetic theory is advanced that the degenerative changes in the tarsus
      result from the combination of local pressure-induced lid ischemia and systemic
      hypoventilation followed by reperfusion oxidation injury.

PMID- 8131405
TI  - Glucocorticoid receptor and interleukin-1 receptor messenger RNA expression in
      corneal cells.
AB  - Interleukin-1 receptor and glucocorticoid receptor messenger ribonucleic acid
      (RNA) sequences coding for the corresponding proteins were detected in corneal
      epithelium, stromal fibroblast, and endothelial cells using the polymerase chain
      reaction and hot blotting. Identification of interleukin-1 receptor mRNA in each
      of the three major cell types of the cornea suggests that interleukin-1 alpha has
      autocrine and/or paracrine roles in the cornea, since previous studies have found
      that interleukin-1 alpha mRNA is produced in corneal epithelial, stromal
      fibroblast, and endothelial cells. Further investigation is needed to determine
      the functions regulated by the interleukin-1 receptor and glucocorticoid receptor
      in the cornea and the role of each in corneal wound healing.

PMID- 8131406
TI  - Photoinactivation of herpes simplex virus by rose bengal and fluorescein. In
      vitro and in vivo studies.
AB  - Rose bengal and fluorescein are photosensitive dyes in widespread use in the
      evaluation of ocular surface diseases, including herpes simplex virus (HSV)
      keratitis. These dyes have recently been shown to penetrate living cells, and
      rose bengal was previously reported to possess antiviral activity. Several
      experiments reported herein suggest that these dyes do possess the potential for
      potent antiviral activity against extracellular virus, but only in the presence
      of light. Rose bengal is substantially more effective in vitro than fluorescein,
      and the effect is greater with increasing concentration of dye and duration of
      light exposure. Electron microscopic evaluation of treated virus showed no
      structural difference from untreated virus, in spite of 4- to 5-log decreases in
      virus titer. Intracellular virus was found to be markedly resistant to
      photoinactivation. In a rabbit model of acute primary HSV keratitis, daily
      application of topical rose bengal followed by light exposure had no therapeutic
      effect, although an adverse effect on culture sensitivity testing was seen.

PMID- 8131407
TI  - Regulation of corneal fibroblast MMP-1 secretion by cytochalasins.
AB  - Cytochalasins B (CB), dihydroB (H2CB), and D (CD) were found to cause loss of
      fibronectin (Fn) from the cell surface of normal rabbit corneal fibroblasts,
      breakdown of F-actin-containing microfilament bundles ("stress fibers"), and
      increase levels of type I interstitial collagenase (MMP-1) in the medium. In
      contrast to the effects of plasmin, the cytochalasins caused withdrawal of cells
      from the Fn mesh but not total loss of the mesh, and the collagenase was
      essentially all in latent form. The results are consistent with the possibility
      that cytochalasins, like plasmin, perturb the alpha 5 beta 1 integrin (Fn)
      receptor. Unlike plasmin, which degrades Fn to result in such a perturbation,
      however, the cytochalasins are thought to do so by directly disrupting
      cytoplasmic F-actin microfilaments associated with focal contact adhesive
      structures, to result in changes in the Fn receptor that cause loss of Fn. Thus,
      plasmin acting extracellularly and cytochalasins acting intracellularly are both
      thought to be able to modulate the secretion (and possibly also the synthesis) of
      MMP-1 by corneal fibroblasts by perturbing the Fn receptor located in the focal
      contact. The presence of all active collagenase after treatment with plasmin, as
      opposed to latent collagenase after treatment with cytochalasin, supports the
      interpretation that the events of secretion and activation of collagenase can be
      uncoupled.

PMID- 8131408
TI  - X-ray and scanning electron microscopic analysis of the structural composition of
      tear ferns.
AB  - Dried tears from keratoconjunctivitis sicca eyes fail to exhibit the fern-like
      crystallization patterns observed with tears from eyes with normal tear function.
      To test our hypothesis that the extent of ferning depends on the ratio of salts
      to protein and mucin in the tear sample, dried tears from six normal subjects
      were subjected to scanning electron microscopy (SEM) and X-ray analyses. X-ray
      diffraction identified sodium chloride and potassium chloride as the major
      components of tear fern crystals. X-ray fluorescence detected the elements
      potassium, chlorine, calcium, and sulfur in the dried tear samples, with sulfur
      indicating the presence of protein and/or mucin. As well as confirming the
      presence of cubic fern nuclei, SEM revealed two kinds of material, having
      crystalline and globular appearances, that are hypothesized to be composed of
      salts and protein/mucin, respectively. Globular material appeared to block
      extension of crystal fern arms or to coat crystalline material, but did not
      crystallize. These findings suggest that tear fern crystals are composed of
      sodium and potassium chloride, with proteinaceous material controlling
      crystallization indirectly by coating crystal faces and blocking fern extension.
      This structural composition is consistent with the hypothesis that the ratio of
      salt to macromolecular species is an important determinant of tear ferning.

PMID- 8131409
TI  - Differential corneal sensitivity to ultraviolet light among inbred strains of
      mice. Correlation of ultraviolet B sensitivity with aldehyde dehydrogenase
      deficiency.
AB  - Adult male mice from four inbred albino strains (SJL/J, NZW/BL, BALB/c HeA, and
      SWR/J) were subjected to ultraviolet radiation (UVR) exposure (302 nm peak
      wavelength, intensity 398 microW/cm2) for 3.25 min and photographed 4 days
      postexposure to assess corneal clouding. Corneal extracts from control
      (unexposed) mice from each strain, were also monitored for aldehyde dehydrogenase
      (ALDH) and alcohol dehydrogenase (ADH) activity and soluble protein content. The
      SWR/J strain exhibited more extensive corneal clouding after UV exposure than did
      the other strains, and control SWR/J mice exhibited a low activity variant
      phenotype for the major ocular ALDH AHD-4, and decreased levels of soluble
      protein in corneal extracts. These data support earlier proposals for a major
      role for ALDH in assisting the cornea in protecting the eye against UVR-induced
      tissue damage.

PMID- 8131410
TI  - Recurrent keratoconus.
AB  - Keratoconus is a progressive, noninflammatory, nonvascular axial corneal ectasia,
      with unclear etiology and pathogenesis. It has a prevalence of 50-230 per 100,000
      and is a bilateral disorder in up to 90% of cases. The onset of keratoconus is
      usually at puberty and progresses over 10-20 years producing an irregular myopic
      astigmatism. The treatment depends on the severity of the irregular astigmatism.
      Advanced keratoconus, which cannot be treated with contact lenses, requires a
      surgical procedure--either penetrating keratoplasty, epikeratophakia, or
      thermokeratoplasty. The results of penetrating keratoplasty are good, with
      success rates of > 90% of the cases. Recurrence of keratoconus following
      penetrating keratoplasty has been previously reported, based on a clinical
      diagnosis, and confirmed by histopathological examination. We report the
      clinicopathologic features of two further cases of recurrent keratoconus.

PMID- 8131411
TI  - Iridoschisis and keratoconus.
AB  - We report herein a patient with iridoschisis and keratoconus. Since the posterior
      layers of the cornea and the iris stroma have a common embryological deviation,
      the combination of these two conditions suggests an inter-related pathogenesis.
      This case is similar to those of patients with progressive essential iris atrophy
      and keratoconus described by Cavanagh.

PMID- 8131412
TI  - Bilateral keratoconus in Crouzon's syndrome.
AB  - Crouzon's syndrome is an autosomal dominant disorder characterized by premature
      craniosynostosis leading to multiple ocular abnormalities and vision loss.
      Strabismus, optic atrophy, exposure keratitis, hypertelorism, nystagmus, and
      unexplained visual loss have been reported. Keratoconus has been described only
      once previously in a patient with other ocular abnormalities. This article
      reports bilateral keratoconus in a patient with Crouzon's syndrome without other
      ocular pathology. We emphasize the importance of early recognition and therapy of
      this treatable cause of decreased vision in Crouzon's syndrome.

PMID- 8131413
TI  - Clinicopathologic study of Gore-Tex patch graft in corneoscleral surgery.
AB  - Three patients with corneal or scleral defects were treated with Gore-Tex
      grafting, including one case of corneal ulcer, one case of Mooren's ulcer, and
      one case of necrotizing scleritis. These eyes remained inflamed after Gore-Tex
      grafting. The interval between grafting and removal ranged from 2 months to 1
      year. Pathologically, none of these grafts showed evident epithelial or fibrous
      tissue ingrowth of the Gore-Tex graft. Fungal inhabitation was noted in one
      graft, and fungal endophthalmitis developed 5 months after graft removal and
      penetrating keratoplasty. Although Gore-Tex offers some advantages, it has
      disadvantages when it is used without adequate conjunctival covering, including
      poor epithelialization, poor adhesion between graft and surrounding tissue, and
      potential infectious route.

PMID- 8131414
TI  - Managing the future of cornea supply and demand: the costs affecting eye banking.

PMID- 8131415
TI  - The methodology of PMN chemotaxis.

PMID- 8131416
TI  - Interleukin-1 regulates the proliferation of leukocytes in human corneal cell
      peripheral blood leukocyte cocultures.
AB  - We have documented the inability of human corneal epithelial-like cells to
      suppress proliferation of peripheral blood leukocytes (PBLs) induced by
      allogeneic PBLs in a mixed leukocyte reaction (MLR). Instead, enhanced
      proliferation of PBLs, albeit small, was consistently noted as indicated by
      uptake of radiolabeled thymidine. Maximum proliferation of PBLs was detected when
      a mixed leukocyte reaction (MLR) was conducted in the presence of corneal cells.
      High levels of interleukin-1 beta (IL-1 beta) were found during MLR irrespective
      of the presence of corneal cells. High levels of IL-1 beta correlated well with
      observed synergistic stimulation of PBL proliferation by corneal cells and
      stimulating allogeneic PBLs. In PBL-corneal cell cocultures, PBLs produced IL-1
      beta; corneal cells contributed large amounts of prostaglandin E2 (PGE2).
      Although indomethacin completely blocked prostaglandin E2 production, it did not
      significantly alter the results. Our data show that PBLs and corneal cells can
      reciprocate each other's presence, and, under appropriate conditions, corneal
      cells can deliver at least one signal to enhance rather than suppress antigen
      driven PBL proliferation. Our data suggest a role for immunoregulatory cytokines
      and prostanoids such as IL-1 beta and PGE2 in these interactions.

PMID- 8131417
TI  - YAG lasers and corneal graft rejection: it may be what meets the eye.

PMID- 8131418
TI  - The association of swallowing dysfunction and aspiration pneumonia.
AB  - The medical literature has emphasized that aspiration of gastric contents or oral
      bacteria is a common cause of aspiration pneumonia. Swallowing disorders have
      been implicated in this disease but not studied at the time that aspiration
      pneumonia was diagnosed. A significant difference was found in the incidence of
      videofluoroscopically confirmed oropharyngeal swallowing problems in a group of
      patients diagnosed with aspiration pneumonia (AP) when compared with patients
      with nonaspiration pneumonia (NAP). Six of the 9 patients in the AP group
      aspirated during the videofluoroscopic evaluation and 2 others were considered to
      be at risk for aspiration. None of the 7 NAP patients demonstrated swallowing
      problems or aspiration. A significant difference in oral transit time also
      occurred between the two groups. Liquid was found to have a significantly faster
      oral transit time than paste or a cookie. Pharyngeal transit times were not found
      to be significantly different. Although there were only a small number of
      patients who met the criteria for this pilot study, a strong association was
      found between swallowing dysfunction and aspiration pneumonia.

PMID- 8131419
TI  - Repetitive contractions of the upper esophageal body and sphincter in achalasia.
AB  - This report describes repetitive contractions in the upper esophageal sphincter
      (UES) and the repetitive upper esophageal spontaneous contractions (RUESCs) of
      patients with achalasia and relates this activity to repetitive contractile
      activity (RCA) recorded in the more distal esophageal body, to intraesophageal
      pressure (IEP), and to lower esophageal sphincter (LES) pressure. Two hundred and
      sixteen consecutive esophageal motility studies from 156 achalasia patients with
      retrospectively assessed. RUESCs were found in 105 patients (67%) and 125 of 216
      studies (58%). General features of the RUESC were (1) coincidence with
      simultaneous repetitive increases in pressure throughout the entire esophageal
      body; (2) amplitude of pressure increases tended to be higher in the proximal
      esophagus; (3) RUESC frequency was different than respiration, except for 6 cases
      where continuous, RUESC and RCA were synchronized with inspiration; and (4)
      RUESCs were positively associated with increased IEP, and with increased LES
      pressure (> 40 mmHg). RCA in the esophageal body was uncommon without RUESC. It
      is concluded that (1) RUESCs are common in achalasia and appear to be closely
      linked to contractile activity in the upper esophageal body; (2) the close
      relationship of RUESC and RCA in the esophageal body to increased IEP and
      elevated LES pressure suggests that esophageal tone is high in these subjects;
      and (3) these findings indicate a potential mechanisms for localization of some
      of the clinical symptoms to the retrosternal and suprasternal areas, for the
      inability to readily belch, and for the development of structural features such
      as a prominent cricopharyngeal bar.

PMID- 8131420
TI  - Abnormal proximal esophageal function in achalasia.

PMID- 8131421
TI  - Deterioration of feeding behavior following surgical treatment of drooling.
AB  - Few adverse effects of the surgical treatment of drooling are reported in the
      literature. This report describes a young man with severe extrapyramidal cerebral
      palsy and profuse drooling whose oral feeding behavior deteriorated following
      bilateral submandibular gland excision and parotid duct rerouting. Before surgery
      the patient had safe, functional oral feeding skills, and eating was enjoyable.
      Following surgery he developed progressive feeding difficulties, weight loss, and
      aspiration pneumonia. His deterioration led to the placement of a feeding
      gastrostomy and the end of all oral feedings. Surgery had a disturbing and
      apparently irreversible negative impact on the patient's quality of life.

PMID- 8131422
TI  - Influence of physical factors on the development of gastroesophageal reflux in
      man: analysis by means of an experimental mechanical model.
AB  - In this paper, the isolated influence of physical factors on the development of
      gastroesophageal reflux in man is analyzed by means of a mechanical model. We
      evaluate the influence of gravity, intraabdominal pressure, intrathoracic
      pressure, transmission of intraabdominal pressure to the high pressure zone,
      filling volume of the stomach, and the existence of a high pressure zone on the
      appearance of gastroesophageal reflux. PH-metry is used to record the episodes of
      reflux in the model. We wish to demonstrate the importance of gravity and
      intraabdominal pressure in the production of reflux. Intrathoracic pressure acts
      as an antireflux mechanism only when associated with a zone of high pressure. The
      intraabdominal pressure may be transmitted to the high pressure zone as a purely
      mechanical effect and the greater gastric filling volume may, when associated
      with the intraabdominal pressure, facilitate reflux without physical changes in
      the high pressure zone (the equivalent of a reduction in the length of the lower
      esophageal sphincter in man). We conclude that this model may help to explain the
      influence of the physical factors mentioned above on the development of
      gastroesophageal reflux in man.

PMID- 8131423
TI  - Prevalence and recovery of aspiration poststroke: a retrospective analysis.
AB  - This retrospective study was undertaken to review aspiration documented by
      videofluoroscopic modified barium swallow (VMBS) examination in a group of
      patients admitted to a stroke rehabilitation unit. Forty-two of 54 patients
      tested demonstrated evidence of aspiration of thin liquids on VMBS performed an
      average of over 5 weeks following the onset of stroke. However, only patients in
      whom there was clinical concern of aspiration (54 of 255 stroke patients admitted
      to the rehab unit) were tested with VMBS evaluation. With this limitation in
      mind, aspiration was demonstrated in at least 9.9% of all unilateral right
      hemispheric patients, 12.1% of unilateral left hemispheric, 24% of bilateral
      hemispheric, and 39.5% of brainstem stroke patients. Of the 42 patients in whom
      aspiration of thin liquids was demonstrated, 31 underwent repeat VMBS studies an
      average of 6 weeks after the initial VMBS. 7 of these 31 (22.6%) no longer showed
      aspiration on VMBS. Eighteen of the 42 patients (43%) clinically stopped
      aspirating over this 6-week period.

PMID- 8131424
TI  - Swallowing/ventilation interactions during oral swallow in normal children and
      children with cerebral palsy.
AB  - Many children with cerebral palsy (CP) suffer from feeding disorders. Twenty
      children with spastic CP and 20 neurologically normal children (age range 6.2
      12.9 years) were monitored with ultrasound imaging of the oral cavity
      synchronized with surface electromyographic (EMG) recordings of masseter and
      infrahyoid muscles and respiratory inductance plethysmograph (RIP) recordings
      during feeding tasks. A lip-cup contact detector signaled contact of the drinking
      cup on the lip during liquid tasks. Children with CP required more time than
      normals for collection and organization of 5 ml and 75 ml liquid boluses for
      swallowing. The ventilatory preparation phase, recovery to baseline resting
      ventilatory pattern after swallowing, and total time for task completion were
      longer in children with CP for 5-ml and 75-ml tasks. The interval from lip-cup
      contact until alteration of ventilation from baseline resting ventilatory pattern
      was longer for children with CP during 75-ml tasks but not for 5-ml tasks. The
      interval from completion of the task-related cookie swallow until initiation of
      the next swallow was longer in children with CP than in normal children. These
      data provide evidence that children with CP manage solid boluses more easily than
      liquid boluses and small liquid boluses more easily than large liquid boluses.
      This investigation statistically confirms empirically based recommendations that
      children with CP be allowed more time to complete feeding tasks and consume small
      volume drinks rather than large volume drinks.

PMID- 8131425
TI  - The Modified Barium Swallow Database.
AB  - Every center that carries out the modified barium swallow (MBS) has a potential
      storehouse of useful clinical and radiological information filed away in the
      patient's files and in the center's video library. The modified barium swallow
      database automates the recording, storage, and analysis of this information. This
      project utilizes a standardized clinical and radiological data form which
      provides a consistent approach to the reporting of the MBS results. The
      information on the data form is entered into the MBS database software program
      for decoding and permanent storage. This database program, designed for the
      computer novice, is menu driven to simplify operation. Once the patient
      information is verified on the computer screen, the program can generate
      different types of reports for clinical and research purposes. The program has
      routines to search for patients with any clinical or radiological findings of
      interest. The ability to group and recall patients with specific findings has
      been an aid in teaching, peer review, and research. The program has been modified
      based upon feedback and experience at three centers in Toronto that have used it
      for 9 months.

PMID- 8131426
TI  - Methodology for detecting swallowing sounds.
AB  - The use of cervical auscultation in the evaluation of the pharyngeal swallow may
      become a part of the clinical evaluation of dysphagic patients. Though its use is
      based on subjective evaluation, an acoustic analysis of swallowing sounds might
      establish more objective criteria in the detection of swallowing disorders. The
      present study sought to investigate three aspects of the methodology for
      detecting swallowing sounds: (1) the type of acoustic detector unit suited to an
      acoustic analysis of the pharyngeal swallow, (2) the type of adhesive suited for
      the attachment of the detector, and (3) the optimal site for sound detection of
      the pharyngeal swallow. An accelerometer with double-sided paper tape was
      selected as the appropriate detector unit because of its wide range of frequency
      response and small attenuation level. Using this detector unit, swallowing sounds
      and noise associated with simulated laryngeal elevation and the carotid pulse
      were acquired at 24 sites on the neck in 14 normal subjects; these signals were
      acoustically analyzed. The determination of the optimal site for detecting
      swallowing sounds was based on the signal-to-noise ratio. The site over the
      lateral border of the trachea immediately inferior to the cricoid cartilage is
      the optimal site for detection of swallowing sounds because this site showed the
      greatest signal-to-noise ratio with the smallest variance. The site over the
      center of the cricoid cartilage and the midpoint between the site over the center
      of the cricoid cartilage and the site immediately superior to the jugular notch
      were also considered to be the most appropriate sites.

PMID- 8131427
TI  - Stethoscope acoustics and cervical auscultation of swallowing.
AB  - Frequency response characteristics of six popular stethoscopes are reported for
      the higher frequency range (to 3000 Hz) to supplement equivalent measurements for
      the lower frequencies (35-1000 Hz) published previously. Spectra of the sounds of
      swallowing from the throat, transduced with an accelerometer, demonstrate
      important frequency composition in this higher range. Two stethoscope models were
      found to have superior transmission characteristics for use in cervical
      auscultation of swallowing sounds.

PMID- 8131428
TI  - Characteristics of dysphagia in children with cerebral palsy.
AB  - Videofluoroscopic modified barium swallow (VMBS) examinations may provide
      clinically relevant information regarding deglutition in children with cerebral
      palsy and dysphagia. A retrospective review of clinical evaluations and VMBS
      studies on 90 consecutive children with cerebral palsy and dysphagia was
      completed. Most children were referred because of concerns regarding airway
      protection during oral feedings. Most children had multiple disabilities and 93%
      were nonambulatory. The majority of children were totally dependent for oral
      feedings (80%). Oral and pharyngeal phase abnormalities were present in almost
      all patients. Abnormalities of deglutition were observed only while swallowing
      specific food textures in the majority of patients. Aspiration of specific food
      textures was significantly more common than aspiration of all food textures (p <
      0.0001). Finally, aspiration was silent in 97% of the patients. VMBS studies can
      provide clinicians with valuable information regarding the most appropriate food
      textures and rates of oral feeding for children with cerebral palsy and
      dysphagia.

PMID- 8131429
TI  - Videofluoroscopic evidence of aspiration predicts pneumonia and death but not
      dehydration following stroke.
AB  - In order to assess the risk of pneumonia, dehydration, and death associated with
      videofluoroscopic evidence of aspiration following stroke, the clinical records
      of 26 patients with aspiration and 33 randomly selected, case-matched, dysphagic
      controls without videofluoroscopic evidence of aspiration were reviewed. The
      videofluoroscopic modified barium swallow technique included 5 ml-thin and thick
      liquid barium, 5 ml barium pudding, and 1/4 cookie coated with barium, plus
      additional 20 and 30 ml of thin liquid barium. Patients were assessed a mean of 2
      +/- 1 SD months poststroke and were followed for a mean of 16 +/- 8 SD months
      poststroke. The odds ratio for developing pneumonia was 7.6 times greater for
      those who aspirated any amount of barium irrespective of its consistency (p =
      0.05). The odds ratio for developing pneumonia was 5.6 times greater for those
      who aspirated thickened liquids or more solid consistencies compared with those
      who did not aspirate, or who aspirated thin liquids only (p = 0.06). Dehydration
      was unrelated to the presence or absence of aspiration. The odds ratio for death
      was 9.2 times greater for those aspirating thickened liquids or more solid
      consistencies compared with those who did not aspirate or who aspirated thin
      liquids only (p = 0.01). Aspiration documented by modified videofluoroscopic
      barium swallow technique is associated with a significant increase in risk of
      pneumonia and death but not dehydration following stroke.

PMID- 8131430
TI  - Cardiac arrhythmias during performance of the flow-volume loop.
AB  - The purpose of our study was to determine the frequency of cardiac ectopy during
      the performance of flow-volume loops. The performance of an adequate flow-volume
      loop entails significant shifts in intrathoracic pressure and oxyhemoglobin
      saturation that could heighten myocardial arrhythmogenicity and lead to increased
      cardiac ectopy. Forty-two male patients referred for performance of flow-volume
      loops were studied with an ambulatory cardiac monitor and an arterial
      oxyhemoglobin saturation monitor during the performance of three flow-volume
      loops before and after administration of an aerosolized, selective beta 2
      agonist. For comparison, the 60 min prior to and after completion of the loop
      testing was monitored with the continuous cardiac monitor. The frequency of
      cardiac ectopy was determined in four patient populations delineated by the
      presence or absence of cardiac, pulmonary, or cardiopulmonary disease. Each group
      was further divided based on the occurrence of arterial oxyhemoglobin
      desaturation during the performance of the flow-volume loop. We found that,
      despite the presence or absence of underlying cardiopulmonary disease or the
      occurrence of oxyhemoglobin desaturation during flow-volume loop performance, the
      number of cardiac ectopies diminished significantly during loop performance when
      compared with the 60-min study period prior to testing. This is in contrast to
      what had been reported previously. We conclude that the flow-volume loop is safe
      to perform in the general population, including those individuals with an
      increased risk of arrhythmias such as those with cardiac or pulmonary disease.

PMID- 8131431
TI  - The restaging of responding patients with limited small cell lung cancer. Is it
      really useful?
AB  - A retrospective review of data on patients entered on two limited small cell lung
      cancer studies of the National Cancer Institute of Canada (BR.3 and BR.6) was
      undertaken to determine the value of restaging and rebronchoscopy in responding
      patients. An economic evaluation was also done. Repeat scans (brain, liver) and
      bronchoscopy were carried out in 190 patients and 5 (2.6 percent) were positive,
      despite other evidence suggesting response. One hundred thirty-nine of 324
      patients who achieved complete response on the two trials underwent
      rebronchoscopy. Among these, 122 (87.7 percent) were negative and eight (5.8
      percent) were inconclusive. Nine (6.5 percent) were positive despite other
      evidence suggesting the patient had achieved a complete response. A small group
      of nine patients with positive rebronchoscopy survived for a shorter time than
      the group with negative or inconclusive rebronchoscopies. The survival difference
      was only statistically significant when analyzed using the log rank test, but it
      was not significant when analyzed by the Wilcoxon test. The economic analysis
      showed that it costs $11,333 per patient reclassified when scans were redone in
      these patients. The cost could even have been higher had we used present-day
      scanning techniques (computed tomography and magnetic resonance imaging),
      although they might be slightly more sensitive. The cost of rebronchoscopy per
      patient reclassified was $14,960. Therefore, we recommend that restaging (scans
      or rebronchoscopy) not be done in responding patients with limited small cell
      lung cancer, thus potentially saving health care dollars as well as reducing
      patient inconvenience with no detrimental effect on survival.

PMID- 8131432
TI  - Pilot study of cardiopulmonary risk from pentoxifylline in adult respiratory
      distress syndrome.
AB  - Neutrophils and cytokines are directly involved in the pathophysiology of adult
      respiratory distress syndrome (ARDS). Pentoxifylline (PTX) has been shown in
      vitro to protect against the inflammatory effects of neutrophils and cytokines.
      The same protective effects have been demonstrated on animal models of lung
      injury. These results suggested that PTX might be useful in patients with ARDS.
      The cardiopulmonary effects of large doses of PTX were evaluated in a pilot study
      performed in six patients with severe ARDS. PTX was administered with an initial
      1-mg/kg bolus, followed by infusion of 1.5 mg/kg/h over 6 h. No significant
      change was observed in the gas exchange and hemodynamic parameters, except for a
      10 percent increase in the heart rate during the infusion period. Our results
      demonstrate that large doses of PTX induced only minor hemodynamic changes
      without worsening in pulmonary gas exchange. Further studies are warranted to
      evaluate human safety and ultimately the effectiveness of PTX in the treatment of
      ARDS.

PMID- 8131433
TI  - Diagnostic fiberoptic bronchoscopy in patients with community-acquired pneumonia.
      Comparison between bronchoalveolar lavage and telescoping plugged catheter
      cultures.
AB  - We compared the diagnostic value of quantitative cultures of bronchoalveolar
      lavage (BAL) and telescoping plugged catheter (TPC) samples in 40 patients with
      moderately severe community-acquired pneumonia (CAP). None had received
      antibiotics previously. BAL quantitative cultures were performed in 13 control
      patients without pneumonia. In 28 (70 percent) patients, TPC cultures yielded >
      or = 10(3) cfu/ml of a pathogenic bacterium in pure culture. In 27 of these cases
      and in four additional cases, BAL cultures yielded > or = 10(3) cfu/ml. BAL
      cultures from the control group were sterile in seven cases, yielded normal flora
      in three cases, and yielded microorganisms thought to be not significant in two
      cases. Microbiologic agreement was reached by both TPC and BAL for 32 (84
      percent) of 38 microorganisms recovered. Quantitative cultures from both
      techniques correlated very well (r = 0.71, p < 0.0001). We conclude that both TPC
      and BAL have similar accuracy to determine etiologic diagnosis of CAP. There was
      good qualitative and quantitative agreement between both techniques.

PMID- 8131434
TI  - Fast-computed tomographic evaluation of the effect of route of breathing on upper
      airway size and function in normal men.
AB  - Nasal obstruction is associated with increased sleep disordered breathing (SDB),
      even in normal subjects. This increase in SDB may result from narrowing of the
      orohypopharyngeal (OHP) or retroglossal segment of the upper airway (UA) due to
      retropositioning of the jaw and tongue base as the mouth is opened and route of
      breathing changed from nasal to oral. It is postulated that significant narrowing
      of the OHP occurs with oral breathing even in the awake state. To ascertain the
      effect of route of breathing on the UA, fast-CT was used to study the UA response
      to the route of breathing in 30 normal, awake men, with each subject breathing
      via the nasal and oral routes under the following conditions: end-inspiration
      during tidal breathing (VTei) and functional residual capacity (FRC). In the
      velopharyngeal (VP) or retropalatal segment of the UA, minimum (Amin) and mean
      (Amean) cross-sectional areas (CSA) decreased 49 +/- 11 percent and 16 +/- 6
      percent, respectively, with oral compared with nasal breathing at FRC. In the
      OHP, Amin at FRC increased by 26 +/- 15 percent with oral compared with nasal
      breathing with no significant change in Amean. Similar changes in CSA of both the
      VP and OHP were observed at VTei. Genioglossal electromyographic (EMGgg) activity
      increased from 12 +/- 1 microV breathing nasally to 27 +/- 4 microV breathing
      orally at FRC. Although the CSA of the VP segment decreased with conversion from
      nasal to oral breathing, Amin of the OHP segment was unexpectedly observed to
      increase with oral breathing. The doubling of EMGgg activity with oral breathing
      suggests that active contraction of the genioglossus may function to increase the
      patency of the OHP segment during oral breathing in supine, awake, normal
      subjects.

PMID- 8131435
TI  - Energy balance in stable malnourished patients with chronic obstructive pulmonary
      disease.
AB  - We have measured caloric intake, energy expenditure, and the thermogenic effect
      of food in ten patients with stable COPD who had a history of involuntary weight
      loss over several years and were malnourished (< 85 percent ideal body weight).
      Each patient completed a 7-day food record. Indirect calorimetry was performed in
      the resting postabsorptive state. After placement of a nasoenteric tube, patients
      were randomly assigned to be refed or sham-fed (mean +/- SD, 16 +/- 3 days),
      following which, metabolic measurements were repeated. Indirect calorimetry was
      also performed before and after a large meal in each patient. Home caloric intake
      was 135 +/- 23 percent of resting energy expenditure. Resting energy expenditure
      was 94 +/- 16 percent of that predicted by the Harris-Benedict equation and did
      not change significantly during inpatient refeeding. Refeeding resulted in weight
      gain (2.4 +/- 1.9 kg, p < 0.02). A large meal caused substantial increases in
      energy expenditure (24 +/- 18 percent), carbon dioxide production (39 +/- 18
      percent), and oxygen consumption (23 +/- 16 percent). We conclude that stable
      malnourished COPD patients consume adequate calories to meet average energy
      requirements and are not hypermetabolic. Inpatient refeeding by nocturnal
      nasoenteric infusion is well tolerated and results in weight gain, but the
      thermogenic effect of a large meal poses a considerable metabolic and ventilatory
      load that could precipitate acute respiratory failure.

PMID- 8131436
TI  - Cardiorespiratory responses to incremental exercise in patients with asbestos
      related pleural thickening and normal or slightly abnormal lung function.
AB  - An increasing number of patients with asbestos exposure are being identified with
      pleural thickening (PT) alone, with little or no impairment in standard tests of
      lung function despite their frequent complaint of dyspnea. We have employed
      incremental cardiorespiratory exercise testing to evaluate the types and
      mechanisms of impairment in 23 such patients. All had normal lung fields on
      radiographic examinations and normal (group 1, n = 12) or minimally reduced
      (group 2A slight restriction, n = 5, group 2B, slight obstruction, n = 6), lung
      function. Excessive ventilation was common in all groups, but especially in group
      2B. Abnormal dead space ventilation (VD/VT) was more frequent in groups 2A (4/5)
      and 2B (4/6) than in group 1 (3/12). It was associated with O2 desaturation in
      three patients in groups 2A and B. Cardiovascular abnormalities were rare (1/23).
      Excessive ventilation and dead space provide a basis for the symptom of dyspnea
      in these patients.

PMID- 8131437
TI  - Antibodies to collagen in patients with idiopathic pulmonary fibrosis.
AB  - STUDY OBJECTIVE: The pathogenesis of idiopathic pulmonary fibrosis (IPF) is
      uncertain. This investigation was undertaken to determine if antibodies to human
      native collagens and their chains are present in the serum of the patients with
      IPF and to examine their relationship with clinical factors. MATERIALS: Serum
      specimens were obtained from 45 subjects. The subjects were separated into three
      distinct groups: group 1 consisted of 16 patients with IPF; group 2a, 9 patients
      with pulmonary fibrotic scars from previous tuberculosis were examined as a
      control group; group 2b, 20 normal individuals matched by age and sex. The
      collagen antigens used in this study consisted of four genetically distinct
      types, I, II, III, IV and their corresponding chains alpha 1(I) + alpha 2(I),
      alpha 1(II), and alpha 1(III). METHODS: a passive microhemagglutination assay was
      used to test the antibody activity in the sera of both patients and controls.
      Titration was performed in microtiter plastic plates, using 0.5 percent cell
      suspension. The specificity of anticollagen antibodies was then tested using an
      absorption serum technique with native collagens and their chains.
      Hemagglutination enhancement and inhibition tests, as well as chromatography,
      were used to determine the type of antibodies. RESULTS: Thirteen of 16 (81
      percent) patients with IPF (group 1) had antibodies against at least one type of
      native collagen or one type of collagen chain in titers up to 1:512. Twelve
      patients exhibited anticollagen antibodies with titers above 1:16. By contrast,
      only 2 of 9 (22 percent) subjects with fibrotic scars (group 2a) and 3 of 20 (15
      percent) normal subjects (group 2b) had antibody activity in titers up to 1:8.
      The differences between group 1 and group 2a and 2b were statistically
      significant, (p < 0.05 and p < 0.001, respectively). There was an inverse,
      statistically significant correlation between duration of the disease (IPF) and
      antibody activity. The correlation coefficient between duration of the disease
      and titers of antibodies to type III collagen (native and/or chain) was higher
      than the correlation coefficient between duration of the disease and titers to
      collagen I. The enhancement and inhibition of agglutination tests, as well as the
      chromatography, showed that the agglutination factors were antibodies of IgG and
      IgM classes. The antibody absorption test revealed that the anticollagen
      antibodies were specific for each collagen and its chain and there was no cross
      reaction. CONCLUSION: This study suggests that the anticollagen antibodies could
      be a marker of IPF activity and may perpetuate the lung tissue inflammation. It
      is still unclear if the autoimmunity of the collagen participates in the
      pathogenesis of IPF or the presence of the anticollagen antibodies is simply an
      epiphenomenon.

PMID- 8131438
TI  - Relationships between characteristics of exposure to pigeon antigens. Clinical
      manifestations and humoral immune response.
AB  - An extensive clinical study has been performed on pigeon breeders in the Canary
      Islands. Three hundred forty-three subjects have participated in this study
      through the filling of a clinical and epidemiologic questionnaire. A venous blood
      sample was also taken from each fancier for a further serologic analysis.
      Detection of specific IgG antibodies was made by an indirect enzyme-linked
      immunosorbent assay (ELISA) using pigeon serum as antigenic material. Twenty-nine
      (8 percent) breeders fulfilled the "classic" pigeon breeders' disease (PBD)
      criteria. One hundred six (31 percent) had rhinitis, 62 (19 percent) had
      immediate bronchial symptoms, and 51 (15 percent) suffered from chronic
      bronchitis. A significant level of specific IgG was detected in 139 (40 percent)
      cases. Rates were correlated with pneumonitis symptomatology (p < 0.001) and with
      chronic bronchitis (p < 0.05). There was a significant association between the
      number of pigeons and the level of sensitization (p < 0.001). Finally, a
      statistical relationship between the intensity of exposure and specific IgG
      response was also found (p < 0.001). Titers of specific IgE could not be related
      either to the reported symptomatology in the questionnaire or to any of the
      exposure parameters analyzed.

PMID- 8131439
TI  - Doppler-derived aortic maximal acceleration. A reliable index of left ventricular
      systolic function.
AB  - We compared maximal acceleration of aortic blood flow (aortic Amax), calculated
      from maximal aortic velocity obtained with a conventional echo-Doppler machine
      with the invasive inotropic index left ventricular end-systolic pressure/left
      ventricular end-systolic volume (LVESP/LVESV) ratio and left ventricular ejection
      fraction (LVEF). Continuous wave (CW) and pulsed wave (PW) Doppler aortic blood
      flows were recorded from the apical view in 16 patients (age, 62.3 +/- 6.4 years)
      within 24 h of left-sided catheterization. The theoretical exponential
      relationship between LVEF and LVESP/LVESV was confirmed in our study population
      (r = 0.92; p < 0.0001). The relationship between aortic Amax determined either by
      CW or PW and LVESP/LVESV was linear (r = 0.92 and 0.93, respectively, p < 0.001),
      whereas the relationship between aortic Amax and angiographic LVEF was
      exponential (PW: r = 84; CW: r = 0.85; both p < 0.001). We conclude that (1)
      aortic Amax, derived from maximal velocity obtained with a conventional machine,
      can be used as an index of left ventricular systolic function, and (2) PW as well
      as CW Doppler signals can be used for this calculation.

PMID- 8131440
TI  - Effects of flecainide and propafenone on systolic performance in subjects with
      normal cardiac function.
AB  - Flecainide and propafenone are effective in suppressing both ventricular and
      supraventricular tachyarrhythmias, but their efficacy is often limited by dose
      related side effects. This study was performed to evaluate noninvasively the
      effects of intravenous flecainide and propafenone on left ventricular systolic
      function indices in a selected population of 40 subjects (28 men and 12 women;
      mean age, 25 years) with normal cardiac structure and performance.
      Echocardiographic indexes of global systolic pump function (ejection fraction
      [EF] and percentage of fractional shortening [percent FS]) as well as
      monodimensional parameters of the intraventricular septum (IVS) and left
      ventricular posterior wall (PW) contractility (percent systolic thickening
      [percent th] and systolic excursion [ex]) were assessed in all subjects at
      baseline, immediately after, and in the early recovery (15 min) after randomized
      injection of either flecainide or propafenone. Heart rate and blood pressure did
      not significantly change after both drugs. A significant increase (p < 0.001) in
      left ventricular systolic internal diameter was observed after both flecainide
      and propafenone; simultaneously a significant decrease of percent FS (p < 0.001),
      EF (p < 0.001), PW percent thickening (th) (p < 0.001), and PWex (p < 0.001 after
      flecainide and p < 0.01 after propafenone) was recorded. These changes were
      comparable and promptly reversible. In analyzing individual data, a marked
      systolic dysfunction was observed in two patients after intravenous flecainide
      (percent FS from 37 percent to 17 percent and from 42 percent to 13 percent; EF
      from 55 percent to 40 percent and from 65 percent to 35 percent, respectively)
      and in one patient after intravenous propafenone (percent FS from 30 percent to
      15 percent; EF from 58 percent to 35 percent). We conclude that both intravenous
      flecainide and propafenone exhibit mild negative inotropic effects leading to a
      moderate and reversible reduction of left ventricular systolic performance;
      however, in some cases, a dramatic impairment of systolic pump function may
      occur, suggesting careful use of both drugs as first-line agents also in normal
      subjects; finally, the true incidence of this deleterious effect is still
      unknown.

PMID- 8131441
TI  - Exercise-induced silent myocardial ischemia in single vessel coronary artery
      disease associated with Q wave infarction. Assessment by thallium 201 single
      photon emission computed tomography.
AB  - PURPOSE: To examine the relationship between the symptom of ischemia and the
      amount of abnormally perfused myocardium, coronary arteriography and exercise and
      redistribution thallium 201 single-photon emission computed tomography (SPECT)
      were analyzed. MATERIALS AND METHODS: The study group consisted of 153 patients
      with single-vessel coronary artery disease; 53 patients had no pathologic Q waves
      (group 1) and 100 patients had pathologic Q waves consistent with the area
      supplied by the diseased vessel (group 2). Twenty normal subjects were used as
      control subjects. The apical, mid, and basal left ventricular levels of the short
      axis view and apical portion of the long-axis view were divided into 20 segments,
      and segmental images were scored blindly on a 0 (normal) to 4 (severely reduced
      uptake) scale. The redistribution score was defined as the thallium 201 defect
      score of exercise subtracted from that of the redistribution image and was used
      as a measure of the amount of ischemic myocardium. RESULTS: The redistribution
      score in 20 control subjects was 0.20 +/- 2.06, and the upper limit of normal
      redistribution score was defined as mean + 2 x SD (4.32). In group 1, 40 of 53
      patients had a redistribution score above the normal range. In group 2, 34 of 100
      patients had a redistribution score above the normal range. Of 40 patients in
      group 1, angina during exercise was observed in 22 patients (55 percent). Twenty
      two patients who had angina had a redistribution score of 15.2 +/- 6.7, while
      those who did not have angina had a score of 13.7 +/- 5.2 (p = NS). Of 34
      patients in group 2, angina was observed in 10 patients (29 percent) during
      exercise. Ten patients with angina had a redistribution score of 10.1 +/- 4.4,
      and those without angina had a score of 9.9 +/- 3.4 (p = NS). CONCLUSION: Thus,
      the incidence of silent ischemia without the Q wave infarct zone was found to be
      higher than that within the ischemic zone without Q wave. Patients with silent
      and symptomatic ischemia during exercise have similar amounts of ischemic
      myocardium demonstrated by tomographic thallium 201 imaging; this was found in
      patients who had Q wave infarction and in those who did not.

PMID- 8131442
TI  - Echocardiographic evaluation of pulmonary artery distensibility.
AB  - The aim of this study was to verify the hypothesis that pulmonary artery (PA)
      distensibility may modify the pattern of right ventricular ejection. Pulmonary
      artery distensibility was evaluated with M-mode measurements of right pulmonary
      artery diameter from suprasternal notch simultaneous with pulmonary pressure
      measurements. Pulmonary artery pressure was measured in 19 subjects, 29 to 75
      years old (mean age, 49 years). Pulmonary artery systolic pressure was 22 to 108
      mm Hg (mean, 52 mm Hg). Pulmonary artery pressure strain modulus (Ep) was
      calculated as follows: PADD x (PASP-PADP)/PADD-PADS (PADS-PA diameter in systole,
      PADD-PA diameter in diastole, PASP-PA systolic pressure, PADP-PA diastolic
      pressure) was 6 +/- 8 10(5) dynes/cm2. Right ventricular outflow tract velocity
      was recorded with pulsed Doppler echocardiography and acceleration times (AT) and
      ejection times (ET) were measured. Log Ep was correlated with pulmonary artery
      systolic and mean pressure (r = 0.90 and r = 0.87, p < 0.0001) but not with age
      (r = 0.30, p = NS). Acceleration time and AT/ET ratio were correlated with log Ep
      (r = 0.73 and r = 0.76, p < 0.001) and with pulmonary artery mean pressure (r =
      0.91 and r = 0.89, p < 0.0001). When pulmonary artery pressure was included in
      multiple analyses, the relationships between Doppler indices and elastic modulus
      did not prove to be significant. These findings emphasize the independence of
      Doppler right ventricular outflow tract velocity indexes used for noninvasive
      evaluation of pulmonary hypertension from pulmonary artery distensibility in a
      clinical setting.

PMID- 8131443
TI  - "Infective" myocardial infarction.
AB  - Four patients who developed acute myocardial infarction (AMI) in the setting of
      systemic febrile illness are described. They were all treated with anticoagulants
      or lytic agents (or both), demonstrating patient coronary arteries following
      infarction. We discuss the pathogenesis and therapeutic implications of AMI
      occurring in this setting.

PMID- 8131444
TI  - Use of BCG vaccine in shelters for the homeless. A decision analysis.
AB  - As a result of many interacting variables, including crowded shelters and limited
      access to health care, homeless persons are at high risk for tuberculosis. Using
      traditional approaches, control of tuberculosis in this population has been
      difficult. Decision analysis was used to investigate the cost-effectiveness of
      BCG (bacillus Calmette-Guerin) vaccination in persons attending homeless
      shelters. This vaccination was cost-effective over a wide range of assumptions.
      Using conservative assumptions, a vaccine that was at least 40 percent effective
      would result in a net cost savings. If the efficacy of the vaccine were 50
      percent, $4,000 would be saved, 12 life-years gained, and 23 cases of active
      tuberculosis prevented for every 1,000 persons vaccinated. Further study of the
      BCG vaccine in homeless persons and other populations at risk is warranted.

PMID- 8131445
TI  - The influence of respiratory acid-base status on adult pulmonary vascular
      resistance before and after cardiopulmonary bypass.
AB  - Respiratory acid-base status has recently been shown to affect pulmonary vascular
      resistance (PVR) in adults following cardiac surgery. The purpose of this study
      was to examine what influence cardiopulmonary bypass has on the pulmonary
      vascular response to changes in respiratory acid-base status. Fifteen consecutive
      patients undergoing aortocoronary bypass were studied under general anesthesia
      both before and after cardiopulmonary bypass. Arterial PCO2 was manipulated by
      the addition of 5 percent carbon dioxide to the breathing circuit. Both before
      and after bypass, PVR increased significantly as PCO2 rose from 30 mm Hg to 50 mm
      Hg (p < 0.05). The PVR returned to baseline as PCO2 was returned to 30 mm Hg.
      These data suggest that increased PVR induced by hypercarbic acidemia is not
      simply a result of the effects of cardiopulmonary bypass on the pulmonary
      circulation. Instead, we conclude that respiratory acid-base status is an
      important determinant of adult PVR. We believe these data may be helpful in the
      treatment of mechanically ventilated patients, since patients are at particular
      risk of having abnormalities develop in respiratory acid-base status.

PMID- 8131446
TI  - Nontuberculous mycobacterial disease in adult cystic fibrosis patients.
AB  - This study was conducted to determine the prevalence of mycobacterial disease in
      an adult cystic fibrosis (CF) population and to determine if there were any
      patients at higher risk for this disease within the group. Sixty-four patients
      (28 women, 36 men), ranging in age from 17 to 50 years were screened. One-step
      purified protein derivative skin testing with controls was performed and sputum
      was taken for examination. Eight of 64 had positive sputum culture for
      nontuberculous Mycobacterium. The CF patients with positive mycobacterial sputum
      cultures tended to be older and to have lower clinical scores than those who did
      not have Mycobacterium organisms in sputum. Guidelines to determine whether
      mycobacterial disease or colonization is present should be pursued for the CF
      population.

PMID- 8131447
TI  - Elevated D dimer in the lungs and blood of patients with sarcoidosis.
AB  - The hypothesis of this study was that D dimer, a specific degradation product of
      cross-linked fibrin, would be increased in the bronchoalveolar lavage (BAL)
      fluids of patients with sarcoidosis and that it would be related to other BAL
      parameters of disease activity. Eight of 10 sarcoidosis patients but none of 18
      healthy volunteers had detectable BAL D dimer by enzyme immunoassay.
      Autoradiography revealed the presence of fibrinogen and D dimer in the BAL fluids
      from sarcoidosis patients. Bronchoalveolar lavage D dimer levels in sarcoidosis
      patients correlated with total BAL cells per milliliter, lymphocytes per
      milliliter, and total protein level, but not macrophages per milliliter. The D
      dimer in the BAL fluids from sarcoidosis patients did not correlate with D dimer
      in the blood. Our findings indicate that BAL D dimer parallels directly the
      lymphocytic alveolitis that characterizes pulmonary sarcoidosis.

PMID- 8131448
TI  - Elevated concentrations of cross-linked fibrin degradation products in plasma. An
      early marker of gram-negative bacteremia.
AB  - PURPOSE: Because coagulant and fibrinolytic activity are increased by endotoxin,
      we hypothesized that concentrations of cross-linked fibrin degradation products,
      sensitive markers of plasmin activity, would be increased in patients with Gram
      negative bacteremia. PATIENTS AND METHODS: Cross-linked fibrin degradation
      products were measured with an enzyme-linked immunosorbent assay (ELISA) based on
      a monoclonal antibody specific for cross-linked fibrin degradation products, and
      with a novel, semiquantitative hemagglutination assay based on the same antibody
      coupled to FAB' fragments from a monoclonal antibody against a universal red
      blood cell antigen. Blood samples were obtained from 100 consecutive emergency
      department patients evaluated for sepsis. RESULTS: Blood cultures were positive
      in 21 percent of the patients, 75 percent (12/21) with Gram-negative organisms.
      Elevations of cross-linked fibrin degradation products (normal < 200 ng/ml) were
      measured by ELISA in all patients (12/12) with Gram-negative bacteremia. The
      hemagglutination assay was positive in ten of these. Detectable increases in
      fibrinolytic activity occurred in all patients with Gram-negative bacteremia,
      even in the absence of clinical signs or laboratory evidence of sepsis or
      disseminated intravascular coagulation. The ELISA and hemagglutination assay had
      negative predictive values for Gram-negative bacteremia of 100 percent and 96
      percent, respectively. CONCLUSION: Elevation of cross-linked fibrin degradation
      products consistent with increased fibrinolytic activity occurs in all patients
      with Gram-negative bacteremia. Accordingly, the lack of elevation may be
      clinically useful in identifying patients less likely to have Gram-negative
      bacteremia.

PMID- 8131449
TI  - Tetracycline and doxycycline inhibit pleural fluid metalloproteinases. A possible
      mechanism for chemical pleurodesis.
AB  - We hypothesized that inhibition of matrix-degrading metalloproteinases (MMPs)
      accounts for a portion of the pleural fibrosis and adhesions of tetracycline
      pleurodesis. MMPs recently have been described in pleural fluid from patients
      with both exudative and transudative effusions. Since tetracyclines are
      recognized inhibitors of other metalloproteinases, we investigated their
      inhibitory capacity in pleural fluid. High concentrations of several different
      tetracyclines reduced MMP activity of pleural fluid by more than 75 percent.
      Lower concentrations (< or = 1 mg/ml) had only modest inhibitory effects. High
      concentration of of tetracyclines also inhibited cell synthesis of MMPs, in
      vitro, but other measures of vital cell function were also impaired. We conclude
      that tetracyclines are effective inhibitors of MMP activity in pleural fluid and
      may also reduce synthesis of MMPs via non specific cell injury. These data
      suggest a possible mechanism to account for tetracycline pleurodesis; ie, an
      inhibition of MMP activity in pleural fluid.

PMID- 8131450
TI  - Stability of blood gases in ice and at room temperature.
AB  - Arterial blood samples from 75 patients were analyzed for PO2, PCO2, and pH at 0,
      15, and 30 min. After the baseline analysis, 60 samples were kept in ice while 59
      samples were left at room temperature. There was a statistically significant
      increase in the PO2 at 15 min and again at 30 min in both groups. There was a
      statistically significant decrease in the PCO2 at 15 min in both groups. There
      were no further changes in the PCO2 at 30 min in either group. There was a
      statistically significant decrease in the pH at 15 min in both groups. There was
      a further statistically significant decrease in the pH at 30 min in the group of
      blood samples left at room temperature but not in those in ice. There is no
      reason to keep arterial blood in ice if blood gas analysis is done within 30 min.

PMID- 8131451
TI  - Bronchial hyperresponsiveness and toluene diisocyanate. Long-term change in
      sensitized asthmatic subjects.
AB  - Long-term change in nonspecific and specific bronchial hyperresponsiveness was
      studied in 16 subjects with asthma induced by toluene diisocyanate (TDI). A
      significant positive correlation between months of follow-up and provocative dose
      inducing a 20 percent fall in FEV1 (PD20FEV1) methacholine was observed in 5 of
      16 subjects. In 4 of these 5 subjects, a PD20FEV1 > 1 mg of methacholine was
      observed 30 to 48 months after the end of TDI exposure. In most subjects,
      nonspecific bronchial hyperresponsiveness did not change. Nine of 16 subjects
      became nonresponsive to TDI at follow-up examination, but only 3 of these showed
      a significant increase in PD20FEV1 methacholine. Seven subjects were still
      responsive to TDI. Recovery from TDI-induced asthma can occur and only after long
      term work cessation. Nonspecific bronchial hyperresponsiveness to methacholine
      can persist even in the absence of bronchial hyperresponsiveness to TDI,
      suggesting permanent chronic damage to mechanisms controlling airway tone.

PMID- 8131452
TI  - Performance of a reservoir nasal cannula (Oxymizer) during sleep in hypoxemic
      patients with COPD.
AB  - STUDY OBJECTIVE: To determine whether a reservoir nasal cannula (RNC) (Oxymizer)
      provides an arterial hemoglobin oxygen saturation as measured by pulse oximetry
      (SpO2) equivalent to that provided by the standard nasal cannula (SNC) during
      sleep in hypoxemic patients with COPD while reducing oxygen flow requirement and
      cost. DESIGN: The study took place in a sleep laboratory for three nights, with
      the first night for acclimatization to the new sleeping environment. In a
      repeated-measures design, on the second and third nights, subjects used the SNC
      for one night and the RNC on another night. The order in which they received the
      two devices was counterbalanced. SUBJECTS: The subjects were patients with COPD
      who had a stable PaO2 of 55 mm Hg or less or had a value of 56 to 59 mm Hg with
      evidence of cor pulmonale or polycythemia (or both) and an FEV1/FVC of less than
      70 percent. INTERVENTIONS: A pulse oximeter was used to measure SpO2. An arterial
      blood gas measurement was taken on each night while the patients with COPD were
      receiving oxygen therapy via the assigned device. An EEG machine was used to
      record measurements of electro-oculography, chin electromyography (EMG), anterior
      tibialis EMG and EEG. MEASUREMENTS AND MAIN RESULTS: There was a statistically
      significant difference between mean SpO2 during sleep (RNC, 91 percent; SNC, 93
      percent; F = 7.89; p = 0.01). Nocturnal SpO2 was less than 90 percent for 24.2
      percent of the time with the RNC and for 17.5 percent of the time with the SNC (F
      = 5.41; p = 0.03), but there was no significant difference in the amount of time
      that SpO2 was less than 85 percent. Compared to the SNC, in 4 of 26 patients with
      COPD, the RNC performed better; in 12 patients with COPD, the RNC performed the
      same, and in 10 patients with COPD the RNC performed worse during sleep. Sleep
      parameters were not significantly different between the two devices. CONCLUSIONS:
      The difference of 2 percent in mean SpO2 is within the range of SpO2 measurement
      error. Therefore, the two devices are equally effective when the sample is
      considered as a whole. Nighttime oximetry is necessary prior to prescription,
      since nighttime efficacy of the RNC cannot be predicted on the basis of daytime
      pulse oximetry.

PMID- 8131453
TI  - Cardiorespiratory fitness evaluation by the shuttle test in asthmatic subjects
      during aerobic training.
AB  - PURPOSE: The purpose of this study was to assess the validity of the 20-m shuttle
      test with 1-min stages (20-MST) to estimate maximal oxygen uptake (VO2 max) and
      its ability to register cardiorespiratory modifications over the course of an
      individualized aerobic training program for mild to moderately asthmatic children
      acclimatized to moderate altitude. METHODS: Forty-eight asthmatic subjects aged
      12 to 17 years performed both a maximal incremental exercise test on a cycle
      ergometer and the 20-MST. Ten of the subjects were then randomly chosen and
      trained three times per week at their ventilatory threshold (Vth) intensity level
      for three months. Another group of ten asthmatic subjects served as control
      subjects. Training intensity was adjusted monthly; heart rate values at Vth were
      increased by the same proportion as the increase in Vo2 max as measured by the 20
      MST. At the end of training, both groups were again evaluated with the two tests.
      The Vo2 max values by direct measurement and by the 20-MST were not significantly
      different for the entire population (46.5 +/- 1.6 vs 47.2 +/- 2.1 ml.min-1.kg-1).
      In addition, the two test results were in close agreement (r = 0.84; p < 0.01).
      After training, a sharp improvement in the direct Vo2 max (44.1 +/- 2.4 to 51.2
      +/- 1.9 ml.min-1.kg-1) was noted in the training group as well as an increase in
      the Vth (25.6 +/- 1.9 to 32.1 +/- 3.4 ml.min-1.kg-1), the maximal power (152 +/-
      7.1 to 185 +/- 3.8 W), and the maximal oxygen pulse (0.24 +/- 0.007 to 0.27 +/-
      0.008 ml.beat-1.kg-1). CONCLUSION: The indirect measure confirmed these results:
      a simultaneous increase in VO2 max (43.7 +/- 2.5 to 53.8 +/- 2.1 ml.min-1.kg-1),
      maximal oxygen pulse (0.22 +/- 0.004 to 0.27 +/- 0.006 ml.beat-1.kg-1), and the
      number of stages completed (7 +/- 1.4 to 10.1 +/- 1.3) was observed. It was
      concluded that the 20-MST has sufficient validity to assess VO2 max and to
      register cardiorespiratory modifications over the course of individualized
      aerobic training programs in mild and moderately asthmatic children. It thus may
      be used to adjust training intensities during these programs.

PMID- 8131454
TI  - Reduction of lung diffusion for carbon monoxide in patients with lung carcinoma.
AB  - A retrospective study to investigate the prevalence and severity of impairment of
      the lung diffusing capacity for carbon monoxide (DCO) in patients with lung
      carcinoma was done using a case-control matched design. A group of 70 patients
      with the histologic diagnosis of lung carcinoma was matched on a one-to-one basis
      with a group of patients with chronic bronchitis and/or pulmonary emphysema
      (COPD); the matching was done based on the FEV1 within 10 percent of each other
      for all pairs. The groups of lung carcinoma and COPD had similar history of
      smoking consumption and pulmonary function, except that the Dco was reduced in
      the carcinoma group (mean +/- SD: 56.4 +/- 12.8 percent of predicted) compared
      with the control group (64.4 +/- 20.1 percent of predicted; p = 0.0027). Among
      the carcinoma group, only one patient had a Dco above 75 percent of the predicted
      value, while in the control group, 22 patients had a Dco above 75 percent of
      predicted values. It appears that Dco is more frequently reduced in patients with
      lung carcinoma than in a group of patients with similar FEV1 and smoking history
      who have chronic bronchitis and/or emphysema but had no evidence of lung
      carcinoma. We speculate that the reduction of Dco in patients with lung carcinoma
      could be due to the concurrent presence of pulmonary emphysema.

PMID- 8131455
TI  - Snoring, hypertension, and the sleep apnea syndrome. An epidemiologic survey of
      middle-aged women.
AB  - The lower limit of the prevalence of sleep apnea syndrome (SAS) was estimated
      among women 40 to 59 years old by a two-stage procedure. In the first stage 2,016
      questionnaires were mailed. The response rate was 75.6 percent. Daytime
      sleepiness was reported by 8.2 percent, habitual snoring by 11.2 percent, and
      intermittent snoring by 21.7 percent. There were altogether 128 women described
      with systemic hypertension and these women were more than twice as often habitual
      snorers. Logistic multiple regression analyses showed almost a threefold increase
      in the predicted prevalence of hypertension among intermittent and habitual
      snorers compared with nonsnorers in the age group 40 to 49 years old and a 60
      percent increase in the 50- to 59-year-old age group. In the second stage, a
      group of 97 women highly suspected of SAS were selected because of their habitual
      snoring and daytime sleepiness. Eventually, 35 of these came for night studies
      and 14 were found to have SAS. Among the 35 women, 12 were hypertensive and nine
      of these had SAS. We estimated the lower limit of the prevalence of SAS to be 2.5
      percent for women 40 to 59 years old. It is concluded that SAS is a relatively
      common occurrence among women, especially postmenopausal ones, and it is strongly
      related to hypertension.

PMID- 8131456
TI  - Pneumococcal bacteremia in three community teaching hospitals from 1980 to 1989.
AB  - STUDY OBJECTIVE: To review the clinical and laboratory findings in a large number
      of patients with pneumococcal bacteremia in the 1980s and identify risk factors
      associated with increased mortality. DESIGN: Retrospective review of medical
      records identified by blood culture logbooks and ICD-9 codes. SETTING: Three
      community teaching hospitals affiliated with a medical school in northeastern
      Ohio. PATIENTS: 385 inpatients with pneumococcal bacteremia admitted between Jan
      1, 1980 and Dec 31, 1989. MEASUREMENTS: Important clinical and laboratory
      information was abstracted from patients' medical records, compiled,
      computerized, and analyzed. MAIN RESULTS: The patients' mean age was 48 years.
      The overall mortality was 25 percent. The mortality increased with age, reaching
      42 percent in patients over 65 years old. For these elderly patients, the
      mortality was higher (55 percent) for patients admitted from nursing homes than
      patients from the community (36 percent). Higher mortality was also associated
      with congestive heart failure (p = 0.001), alcoholism/cirrhosis (p = 0.02),
      diabetes mellitus (p = 0.05), and malignancy (p = 0.02). A platelet count less
      than 150,000/mm3, renal dysfunction (serum creatinine > 2 mg/dl), and the number
      of lobes involved were also associated with mortality. Patients receiving
      standard therapy (penicillin, ampicillin, erythromycin, or cephalosporins) had
      lower mortality. Of the previously specified risk factors for mortality, only
      age, whether standard therapy was administered, the number of lobes involved, and
      the serum creatinine level proved to be independent risk factors according to
      logistic regression. CONCLUSIONS: The overall mortality from pneumococcal
      bacteremia has not decreased during the past 40 years. Risk factors associated
      with increased mortality were identified. Prevention by immunization with
      polyvalent pneumococcal polysaccharide vaccine should be practiced more widely.

PMID- 8131457
TI  - A new oxygen applicator for simultaneous mouth and nose breathing.
AB  - We have developed a new O2 applicator to try to overcome the problems of long
      term oxygen therapy that ensures a sufficient oxygen supply for both nasal and
      oral breathing and prevents mucosal irritation. Placed on the upper lip, it is
      unobtrusive. The principle is as follows: due to an enlarged outlet area,
      turbulence occurs and the oxygen is reduced. Thus, an oxygen cloud is formed that
      can be inhaled by both mouth or nose. The efficiency of our O2 applicator was
      compared with a face mask in six healthy subjects and patients with COPD. A
      similar increase in PO2 was found up to an oxygen flow of 2 L/min for nasal and
      oral breathing. Mild hypercapnia resulted in three patients with COPD only when a
      face mask was used and only when patients breathed through the nose. All patients
      preferred the new applicator.

PMID- 8131458
TI  - Effects of inspiratory flow rate alterations on gas exchange during mechanical
      ventilation in normal lungs. Efficiency of end-inspiratory pause.
AB  - The influence of inspiratory flow rate (TI), without changing respiratory
      frequency, tidal volume, and FIO2, was investigated in 11 normal lungs in
      patients undergoing mechanical ventilation because of central respiratory failure
      due to stable coma. The patients were anesthetized and paralyzed. They first
      received a conventional ventilation (TI = 25 percent, pause = 10 percent) and
      then, were submitted to four different TI values, randomly administered without
      any end-inspiratory pause (EIP) (TI = 20 percent; TI = 33 percent; TI = 50
      percent; TI = 67 percent). In the middle and at the end of the procedure, a
      return to basal conditions was introduced. At each ventilator setting, the
      following were obtained: respiratory flow (Pneumotachograph Fleish No. 2), airway
      pressure, FRC changes (inductive plethysmography), arterial and mixed venous
      blood gases, hemodynamic data, and VA/Q ratios distribution using multiple inert
      gases technique. EIP suppression provides a significant increase in VA/Q mismatch
      (until TI = 50 percent) and in shunt effect (between 3 and 9 percent of cardiac
      output [QT]). The absence of simultaneous PaO2 change is due to increasing PVO2
      linked to a higher QT. The shorter the TI, the higher the PaCO2 connected with a
      relative alveolar hypoventilation. However, increasing TI without EIP
      significantly decreases ventilation distribution inequalities. This improvement
      is concomitant with a rise in FRC (FRC67-FRC20 = 0.340 +/- 0.450, p < 0.05)
      without any change in other variables or auto-PEEP production. In summary, in
      subjects with very slight mechanical lung impairment (peak inspiratory pressure =
      20.5 +/- 5.3 cm H2O at TI = 20 percent and 15.2 +/- 3.3 cm H2O at TI = 67
      percent), this study confirms the deleterious effect of EIP suppression and TI
      decrease. One can compensate for this effect of EIP absence by increasing TI as
      soon as it reaches TI = 67 percent, ie, inverse ratio ventilation.

PMID- 8131459
TI  - The effects of cigarette smoking on pulmonary hemodynamics.
AB  - Neutrophils are delayed in transit in the pulmonary circulation during smoking
      which could reflect smoke-induced changes in local hemodynamics. The purpose of
      this study was to measure the changes in pulmonary hemodynamics during cigarette
      smoking in both healthy smokers and patients with COPD with and without pulmonary
      hypertension. In eight healthy smokers, cigarette smoking decreased the transit
      time of technetium-99m-labeled red blood cells, associated with an increase in
      cardiac output and a fall in the pulmonary blood volume index. In patients with
      COPD, the cardiac index also increased during smoking associated with a small
      increase in pulmonary arterial pressure only in those patients with pulmonary
      hypertension. However, pulmonary vascular resistance fell. These changes in
      pulmonary hemodynamics during cigarette smoking could not account for the
      increased neutrophil sequestration that has been observed previously in the lungs
      during smoking.

PMID- 8131460
TI  - Dynamic respiratory patterns after laparoscopic cholecystectomy.
AB  - Important alterations in respiratory function have been observed after open
      cholecystectomy. These include a decrease in the abdominal tidal volume, forced
      vital capacity, and forced expiratory volume at 1 s. Laparoscopic cholecystectomy
      is a new procedure allowing removal of the gallbladder without a subcostal or
      midline incision. The result is less postoperative pain and earlier ambulation.
      This study sought to determine whether changes in rib cage and abdominal wall
      motion are different after laparoscopic than open cholecystectomy. Twelve
      otherwise healthy patients underwent respiratory inductive plethysmography prior
      to and one day after laparoscopic cholecystectomy. Frequency of resting breathing
      increased 29 percent after laparoscopic cholecystectomy (p = 0.03), while
      abdominal motion decreased 32 percent (p = 0.03). During coached abdominal
      breathing, rib cage tidal volume increased 70 percent (p = 0.005) and abdominal
      tidal volume decreased 29 percent (p = 0.01). These alterations in respiratory
      pattern after laparoscopic cholecystectomy were smaller in magnitude than those
      reported following the open procedure.

PMID- 8131461
TI  - Allergen-induced recruitment of inflammatory cells in lavage 3 and 24 h after
      challenge in allergic asthmatic lungs.
AB  - To determine whether a link exists between the recruitment of inflammatory cells
      in the airways on a bronchial and bronchoalveolar level and the development of
      allergen-induced increase in bronchial hyperresponsiveness after allergen
      challenge, we used bronchial lavage and bronchoalveolar lavage to assess the
      airway responses to allergen. Twelve symptomatic atopic asthmatics were studied.
      In all patients bronchial and bronchoalveolar lavage was performed before, 3 h,
      and 24 h after allergen challenge. Monoclonal antibodies were used directed
      against T cells (CD3, CD4, CD8) and the eosinophil cationic protein (EG2). Eight
      patients showed a dual asthmatic response; four patients showed only an early
      asthmatic reaction after allergen challenge. Clear differences were found between
      bronchial and bronchoalveolar lavage. Activated eosinophils (EG2) were
      significantly increased both at 3 h (p = 0.01) and 24 h (p = 0.005). The number
      of activated eosinophils was significantly higher in the dual responders. A
      correlation was observed between the severity of the late asthmatic reaction
      (LAR) and the number of epithelial cells in the bronchial recovery at 3 h, but
      not at 24 h, in patients who clinically developed a LAR. No significant changes
      in the number of CD3, CD4, and CD8 cells 3 and 24 h after the challenge both in
      the bronchial and bronchoalveolar recovery were observed. We conclude that the
      number of activated eosinophils in bronchial lavage is associated with the
      development of the LAR and allergen-induced increase in bronchial
      hyperresponsiveness.

PMID- 8131462
TI  - Effects of short-term oxygenation changes on acute lung injury patients
      undergoing pressure support ventilation.
AB  - We investigated the effects of short-term oxygenation changes upon the
      neuromuscular respiratory drive (airway occlusion pressure [P0.1]), minute
      ventilation (VE), and respiratory rate (RR) in 12 acute lung injury patients
      undergoing pressure support ventilation. We ventilated the patients first at a
      high level (H1) of oxygenation, then at intermediate (I), at low, and again at
      the high (H2) level. The H1 and H2 periods showed no differences. In the H1, I,
      and L periods, PaO2 was 158 +/- 68, 75 +/- 12, and 55 +/- 6 mm Hg, respectively.
      Decreasing oxygenation caused very significant increases in VE, RR, and P0.1.
      Differences in RR, VE, and rapid shallow breathing index were significant at step
      H1 versus I. Changes in P0.1 appeared to be higher when the H1 value was higher
      than normal. An arterial oxygenation target higher than the generally accepted 60
      mm Hg level may decrease both RR and VE.

PMID- 8131463
TI  - Intrapleural streptokinase as adjunctive treatment for persistent empyema in
      pediatric patients.
AB  - Successful treatment of persistent empyema by intrapleural streptokinase is
      described in five pediatric patients. Their ages ranged from 18 months to 7
      years. All experienced dramatic improvement in the resolution of their empyemas
      following intrapleural streptokinase. Improved chest tube drainage occurred
      concurrently with clinical improvement. Intrapleural instillation of
      streptokinase appears to be a safe adjunctive therapeutic tool to facilitate
      drainage of persistent empyema in the small number of pediatric patients in whom
      it has been employed. Additional study will be required to further assess the
      long-term therapeutic efficacy and consequences of intrapleural streptokinase
      therapy.

PMID- 8131464
TI  - Chronic obstructive pulmonary disease mortality. A role for altitude.
AB  - A map of US COPD mortality rates by state suggested that the relative hypoxia of
      increased altitude may be independently associated with COPD mortality. This was
      investigated using linear regression analysis of 1986 state-specific data on COPD
      mortality rates, history of cigarette consumption, and altitude. County seat
      altitudes and county populations were used to calculate the median altitude of
      state residents. We found independent significant associations between COPD and
      both smoking and altitude. State COPD mortality rose by 1/10(5) for every 5.4
      increase in mean packs consumed per capita per year or for each 95-m increase in
      resident altitude. There was no association between altitude and smoking. If
      increased altitude does contribute to COPD mortality, persons with this disease
      may benefit from down-migration.

PMID- 8131465
TI  - Chest roentgenographic guidelines in the selection of patients for fiberoptic
      bronchoscopy.
AB  - We conducted this study to define the value of fiberoptic bronchoscopy (FOB) in
      the evaluation of chest radiographic abnormalities and to provide guidelines for
      fiberoptic bronchoscopy on the basis of chest radiographic appearances.
      Fiberoptic bronchoscopy without fluoroscopy was carried out in 530 patients, 455
      male and 75 female, aged 19 to 85 years, during a 1-year period at Chest
      Department, Veterans General Hospital, Taipei. Of 530 patients, 19 (3.6 percent)
      had normal chest radiographs, and the remaining 511 (96.4 percent) patients had
      abnormal chest radiographs. Overall diagnostic yield of FOB was 55.4 percent in
      patients with abnormal chest radiographs and 52.6 percent in patients with normal
      chest radiographs. On the basis of radiographic findings, patients with lobar
      collapse (87.0 percent), hilar abnormalities (81.8 percent), pericardial
      effusions (66.7 percent), mass lesions (> 4 cm) (65.7 percent), and pleural
      effusions (64.9 percent) were most frequent to obtain a positive diagnosis via
      bronchoscopy (p < 0.001). Of 530 patients; mass lesion was the most frequent
      abnormality on bronchoscopy and had the highest incidence of providing a positive
      diagnosis (36.2 percent) (p < 0.001). A predilection of mass lesion on
      bronchoscopy was seen for chest radiographic features of lobar collapse (64.8
      percent) and mass (> 4 cm) (47.0 percent) (p < 0.001). Of 19 patients with normal
      chest radiographs, a correct diagnosis was made in 4 (21.1 percent) with
      bronchoscopic findings of mass lesions, 3 (15.8 percent) with endobronchial
      abnormalities, and 3 (15.8 percent) patients with abnormal bronchial mucosa.
      Indeed, the decision to perform bronchoscopy should be guided by many factors
      other than chest radiograph. In this study, however, emphasis has been placed on
      the incidence of positive diagnosis via bronchoscopy on the basis of chest
      radiographic patterns. In this respect, we believe that in patient with lobar
      collapse, hilar abnormality, pericardial effusion, mass lesion (> 4 cm), and
      pleural effusion on the chest radiograph bronchoscopy should be considered.

PMID- 8131466
TI  - Exposure to microorganisms associated with allergic alveolitis and febrile
      reactions to mold dust in farmers.
AB  - STUDY OBJECTIVE: To compare exposure to microorganisms associated with allergic
      alveolitis (AA) and with febrile reactions to inhaled mold dust (organic dust
      toxic syndrome [ODTS]) in farmers and in normal subjects. DESIGN: A prospective
      study in which exposure was evaluated within two weeks of medical consultation
      for AA or ODTS. Samples were collected during normal farming (background) and
      during the handling of materials associated with disease or causing maximal
      exposure in reference farms (worst case). SETTING: Swedish farms PARTICIPANTS:
      Eleven farmers with a confirmed diagnosis of AA from ten farms, 16 subjects with
      symptoms of ODTS from 12 farms, and 17 reference farmers. MEASUREMENTS AND
      RESULTS: Worst-case samples representative of the exposure preceding disease were
      obtained on four farms where five farmers had had AA; the samples contained on
      average 2.6 +/- 1.8 x 10(9) (SD) spores/m3 of air. On six farms where nine
      farmers had had ODTS, representative samples averaged 13 +/- 13 x 10(9)
      spores/m3, and on reference farms this figure was 0.12 +/- 0.20 x 10(9)
      spores/m3. The daily spore dose associated with allergic alveolitis was 2 x 10(9)
      spores/d, which was ten times higher than on reference farms. The average dose
      associated with ODTS was 2 x 10(10) spores. Worst-case samples, collected during
      10 to 30 min, contributed to more than 90 percent of the day exposure on farms
      where AA or ODTS had occurred. CONCLUSION: Allergic alveolitis was associated
      with high exposure levels on most weekdays for weeks, and ODTS was associated
      with extreme exposure occurring on a single day. There was no correlation with
      individual spore types and disease and the present results are compatible with a
      hypothesis that common cell wall components of microorganisms may cause "toxic"
      symptoms and stimulate immune reactions.

PMID- 8131467
TI  - Invasive evaluation of patients with heat stroke.
AB  - Right-heart catheterization was performed in ten patients who suffered heat
      stroke on their pilgrimage to Mecca, Saudi Arabia. The group included seven men
      and three women who had mean rectal temperatures of 42.4 degrees C. Other
      findings included the following: heart rate (mean, 120 beats/min); cardiac output
      (mean, 8.2 ml/min/m2); arterial pressure (mean, 65 mm Hg); cardiac indices (mean,
      4.4 ml/min/m2); right atrial pressure (mean, 6 mm Hg); pulmonary capillary wedge
      pressure (mean, 10 mm Hg); systemic vascular resistance (mean, 684 dyne.s.cm-5);
      pulmonary vascular resistance (mean, 86 dyne.s.cm-5); oxygen delivery (mean 837
      ml/min/m2); oxygen consumption (mean 160 ml/min/m2); mixed venous oxygen tension
      (mean, 56 mm Hg); and shunt fraction (mean, 20 percent). Nine patients survived.
      One, who had a cardiopulmonary arrest before any treatment could be administered,
      died.

PMID- 8131468
TI  - Prediction of minimal pressure support during weaning from mechanical
      ventilation.
AB  - Our goal was to evaluate the accuracy of a prediction equation that estimates the
      minimal level of pressure support (PS) required to overcome the resistance of the
      ventilator circuit and the endotracheal tube during mechanical ventilation. We
      calculated the minimal PS (PSmin) by means of the relationship between airway
      resistance and peak inspiratory flow rate during mechanical ventilation.
      Measurements of breathing pattern, flow rates, work of breathing (WOB), pressure
      time product (PTP), and PEEPi were made during several modes of ventilation
      (PSmin, PSmin + 25 percent, PSmin-25 percent, flow by, CPAP 0 cm H2O) and while
      breathing through an endotracheal tube (ETT) and spontaneous breathing (EXT). The
      WOB was significantly higher during EXT than PSmin, PSmin-25 percent, and ETT
      (1.04 vs 0.45, 0.54, and 0.74 J/L, respectively, p < 0.05). An unexpected finding
      was a higher WOB and PTP during EXT as compared with ETT in six of seven of our
      patients (1.04 vs 0.74 J/L). Examination of breathing pattern and flow volume
      loops in these two breathing modes raises the possibility that the post-EXT
      pathology increases in WOB is related to upper airway abnormality. Because of
      this, our predicted PSmin underestimated the WOB required for spontaneous
      breathing immediately post EXT.

PMID- 8131469
TI  - A computer-controlled ventilator weaning system. A clinical trial.
AB  - The purpose of this study was to determine if a computer-directed weaning system
      could wean patients with complex medical problems from mechanical ventilation and
      appropriately respond to signs of respiratory failure more effectively than
      traditional physician-directed weaning methods. In a prospective, randomized,
      controlled study, we tested the system in 15 patients who had required prolonged
      mechanical ventilation and met predetermined weaning tests. Patients were
      randomly assigned to one of two groups: (1) automatic, computer-directed weaning
      or (2) physician-controlled weaning. The computer-directed system decreased or
      increased the synchronized intermittent mandatory ventilation rate and pressure
      support (PS) based on predetermined limits of patient respiratory rate (RR) and
      tidal volume (TV). Pulse oximeter oxygen saturation was monitored, and alarms
      were triggered by an oxygen saturation of < 90 percent. In the physician control
      group, weaning progressed with SIMV rate and PS reduction, as judged appropriate
      by the physician. Nine patients were assigned to the computer group; six patients
      were assigned to the control group. The average patient age was 64.8 +/- 14.9
      years for the computer group, 65.2 +/- 22.7 years for the control group. The
      average time on mechanical ventilation prior to weaning was 13.4 +/- 7.8 days for
      the computer group and 14.5 +/- 11.1 days for the control group. Seven of the
      nine computer group patients weaned within 48 h of the study, with an average
      time to wean of 18.7 +/- 5.9 h. All seven were breathing spontaneously 48 h after
      weaning. Two of the six control group patients weaned within 48 h of the study,
      with an average time of 25.6 +/- 5.6 h. Both patients who weaned were placed back
      on mechanical ventilation within 30 h. The number of arterial blood gas samples
      drawn during the study was 1.4 +/- 0.7 for the computer group, 7.2 +/- 4.3 for
      the control group. The number of minutes per hour outside acceptable limits of RR
      > 30, RR < 8, or TV < 5 ml/kg was 3.2 +/- 2.8 min for the computer group and 6.6
      +/- 4.1 min for the control group. The study suggests that use of the computer
      directed weaning system results in fewer arterial blood gas samples, shorter
      weaning times, and less time spent outside acceptable RR and TV parameters.

PMID- 8131470
TI  - Controlled trial of a continuous irrigation suction catheter vs conventional
      intermittent suction catheter in clearing bronchial secretions from ventilated
      patients.
AB  - Continuous irrigation-suction catheter (Irri-cath) is a double-lumen device that
      allows for simultaneous saline solution infusion and aspiration. This system may
      theoretically be more effective than conventional dry intermittent suction due to
      its vortex principle. To test this hypothesis, we performed 200 suction maneuvers
      in 20 ventilated patients. Identically shaped catheters were used in a randomized
      sequence. For the same individual, we used equal instilled saline solution volume
      (40 ml), vacuum pressure (-180 cm H2O), and ventilatory parameters. Effectiveness
      of suction was determined by measuring the total aspirated volume, the dry
      lyophilized weight of secretion, the corrected dry weight (dry weight-weight of
      instilled salt), and protein concentration. No difference in heart rate,
      respiratory frequency, O2 saturation, systemic blood pressure, peak inspiratory
      pressure, or patient discomfort was found when the two modalities were compared;
      however, the total volume of secretions collected, the dry weight, the corrected
      dry weight, and the protein concentration were significantly higher with
      continuous irrigation suction catheter when compared with the conventional method
      (p < 0.05). The suction time was shorter with the Irri-cath (p < 0.05). We
      conclude that the Irri-Cath is more effective than conventional intermittent
      suction catheter in clearing bronchial secretions in patients on mechanical
      ventilation.

PMID- 8131471
TI  - Preoperative and intraoperative factors associated with prolonged mechanical
      ventilation. A study in patients following major abdominal vascular surgery.
AB  - A study of 51 patients undergoing elective major abdominal surgery was carried
      out to determine the incidence of postoperative respiratory failure requiring
      mechanical ventilation for more than 24 h and which preoperative and
      intraoperative factors are associated with this respiratory complication.
      Mechanical ventilation for more than 24 h was required in 12 of the 51 patients.
      These 12 patients had a significantly longer stay in the intensive care unit and
      in the hospital than the patients who were successfully extubated in the
      postoperative period. Also, there was a trend for a higher mortality in the
      ventilated group compared to the group of patients who did not require
      postoperative ventilation. Preoperative abnormalities in FEV1 did not identify
      which patients were destined to require postoperative ventilation. Significant
      differences for the ventilated versus the nonventilated patients included a
      longer history of cigarette smoking, a lower preoperative PaO2, and a large
      intraoperative blood loss.

PMID- 8131472
TI  - Acute cardiogenic shock in a 62-year-old man.

PMID- 8131473
TI  - Right-sided hemothorax and recurrent abdominal pain in a 34-year-old woman.

PMID- 8131474
TI  - Arginine vasopressin induces endothelium-dependent vasodilatation of the
      pulmonary artery. V1-receptor-mediated production of nitric oxide.
AB  - Infusion of arginine vasopressin (AVP) decreases pulmonary artery pressure. To
      determine whether this is due to stimulated release of endothelium-derived
      relaxing factor in the pulmonary circulation, the authors studied segments of
      canine pulmonary artery suspended in organ chambers for measurement of isometric
      force. In segments in which contraction was induced with phenylephrine (10(-6)
      mol), AVP (10(-12) to 10(-7) mol) produced concentration-dependent relaxation in
      segments with endothelium but not in segments without endothelium. Greater
      concentrations of AVP (3 x 10(-7) to 3 x 10(-5) mol) produced comparable
      contraction in segments with or without endothelium. Endothelium-dependent
      vasodilation in response to AVP was inhibited by NG-nitro-L-arginine (10(-4) mol)
      and NG-monomethyl-L-arginine (L-NMMA) (10(-4) mol), inhibitors of nitric oxide
      synthesis from L-arginine. The inhibitory effect of L-NMMA was attenuated by L
      arginine (10(-4) mol). Endothelium-dependent vasodilation in response to AVP was
      inhibited reversibly by the vasopressin V1-blocker. Arginine vasopressin induces
      release of endothelium-derived nitric oxide through action on endothelial V1
      receptors. Endothelium-derived nitric oxide mediates vasodilatation, which may
      explain decreased pulmonary resistance during AVP infusion.

PMID- 8131475
TI  - Current concepts in cerebral protection.
AB  - In the past, physicians viewed ischemic injury as an irreversible event. Modern
      science has shown that this view is incorrect and that ischemic neuronal damage
      is an ongoing, active process that might be amenable to various therapies. Figure
      2 illustrates some of the possible sites where these therapies might be active.
      Pending evidence of their effectiveness, cerebral protection can best be achieved
      by maintaining adequate CPP and CBF during periods when patients are at risk for
      cerebral ischemia, restoring perfusion after ischemia occurs, and optimizing the
      metabolic milieu of the ischemic penumbra.

PMID- 8131476
TI  - Diagnosis of unilateral mainstem bronchial obstruction following single-lung
      transplantation with routine spirometry.
AB  - Single-lung transplantation has become a treatment option for many patients with
      advanced pulmonary disease. Recent advances in surgical technique and refined
      immunosuppressive regimens have led to improvement in long-term outcomes, but
      postoperative complications, including airway disorders, remain problematic.
      Serial spirometry with flow-volume loops is sensitive in detecting early small
      airway disease associated with lung allograft rejection or bronchiolitis
      obliterans, but its role in the diagnosis of large-airway disease in the
      posttransplantation setting has not been delineated. In this report, we describe
      a novel alteration in the configuration of the flow-volume loop in a patient who
      developed unilateral mainstem bronchial obstruction following single-lung
      transplantation for severe emphysema. Surveillance spirometry performed 6 weeks
      after transplantation demonstrated a new initial plateau in the maximal
      expiratory flow-volume curve suggestive of a variable intrathoracic airway
      obstruction. This unique aberration in the flow-volume curve sheds new insight
      into the physiologic abnormalities of spirometry in patients receiving lung
      transplants.

PMID- 8131477
TI  - Euthanasia and assisted suicide. Ethics and politics.

PMID- 8131478
TI  - Restrictive chest bellows disease and frontometaphyseal dysplasia.
AB  - We describe a patient with frontometaphyseal dysplasia (FMD), restrictive chest
      bellows disease, hypercapnic respiratory failure, and cor pulmonale. Treatment
      with intermittent supplemental oxygen, nocturnal nasal volume ventilation, and
      posture modification was successful in partial resolution of chronic
      hypoventilation and excessive daytime somnolence.

PMID- 8131479
TI  - Pneumatoceles causing respiratory compromise. Treatment by percutaneous
      decompression.
AB  - Pulmonary pneumatoceles are uncommon but generally benign, thin-walled
      parenchymal air collections arising in association with acute pneumonia. Rarely,
      they may attain such size as to severely affect respiration. We describe the
      percutaneous placement of multiple drains in a patient with pneumonia due to
      atypical measles and large pneumatoceles. Decompression via tubes resulted in
      improved ventilation and acceleration of recovery.

PMID- 8131480
TI  - AIDS and malignant mesothelioma--is there a connection?
AB  - A 35-year-old male homosexual, a former intravenous drug abuser, was found to be
      human immunodeficiency virus (HIV) positive in 1984. He developed AIDS in 1987
      and began treatment with zidovudine in 1989. One year later he developed left
      apical pleural blebs, a pneumothorax and an exudative pleural effusion. A
      malignant mesothelioma developed at the pleural blebs in the left apex. He was
      treated with adriamycin but rapid progression of the malignancy occurred and he
      died three months later. At autopsy, a malignant mesothelioma, causing
      respiratory failure and death, was found. The patient had no exposure to asbestos
      and asbestosis was not present at autopsy. We postulate that the development of
      malignant mesothelioma was probably related to HIV immune suppression or HIV
      and/or cytomegalovirus or zidovudine and is a complication of AIDS similar to the
      development of other malignant neoplasms in patients with AIDS.

PMID- 8131481
TI  - Chronic respiratory failure due to bilateral vocal cord paralysis managed with
      nocturnal nasal positive pressure ventilation.
AB  - A patient with bilateral vocal cord paralysis developed chronic respiratory
      failure. Treatment with nocturnal inspiratory positive airway pressure via nasal
      mask improved symptoms and reduced hypercapnia.

PMID- 8131482
TI  - Resolution of severe intrapulmonary shunting after liver transplantation.
AB  - A major complication of hepatic cirrhosis is arterial hypoxemia, often the result
      of intrapulmonary arteriovenous shunting. While previously such hypoxemia was
      thought to preclude successful hepatic transplantation, more recent studies have
      suggested that hepatic transplantation should be considered if the hypoxemia is
      corrected by supplemental oxygen. We report the findings in a cirrhotic patient
      with severe hypoxemia associated with intrapulmonary arteriovenous shunting. The
      patient did not respond to supplemental oxygen (PaO2 < 40 mm Hg on O2 at 4
      L/min). The patient underwent successful hepatic transplantation, with complete
      resolution of intrapulmonary shunting. We believe that patients with cirrhosis
      associated intrapulmonary shunting, even with hypoxemia resistant to supplemental
      oxygen, are acceptable candidates for hepatic transplantation.

PMID- 8131483
TI  - Transient ST elevation and left ventricular asynergy associated with normal
      coronary artery in aneurysmal subarachnoid hemorrhage.
AB  - A 62-year-old woman presented with transient ST segment elevation and left
      ventricular asynergy in an acute phase of subarachnoid hemorrhage (SAH). A
      coronary arteriogram during ongoing ST elevation showed no fixed stenoses or
      spasm. These findings refute epicardial coronary vasospasm as a cause of
      transient ST elevation and left ventricular asynergy in patients with SAH.

PMID- 8131484
TI  - Regression of cardiac insufficiency after ambulatory intravenous deferoxamine in
      thalassemia major.
AB  - A case of severe cardiac failure due to iron overload in a patient with beta
      thalassemia major is reported. The patient was successfully treated with high
      dose ambulatory intravenous deferoxamine (desferrioxamine). This type of
      chelation appears to be a valuable alternative to subcutaneous deferoxamine
      administration in the presence of severe iron overload.

PMID- 8131485
TI  - Ectopic intrapulmonary thyroid.
AB  - An 83-year-old woman underwent resection of a pulmonary tumor. Histologic
      examination of the tumor demonstrated thyroid follicles without evidence of
      malignancy or teratomatous elements. Developmental anomaly may account for the
      ectopic intrapulmonary thyroid, which, to our knowledge, has not been reported in
      the literature.

PMID- 8131486
TI  - Antemortem diagnosis of an endomyocardial breast cancer metastasis by transvenous
      endomyocardial biopsy.
AB  - Endomyocardial breast cancer metastases are extremely rare and have previously
      been diagnosed antemortem only through median sternotomy and cardiotomy. We
      report a case of endomyocardial breast cancer metastasis which was diagnosed
      antemortem by transvenous endomyocardial biopsy.

PMID- 8131487
TI  - Hemoptysis as a presentation of mild hemophilia A in an adult.
AB  - It is not unusual for mild hemophilia A to escape detection into adolescent years
      and it is often detected following dental extractions or other mild trauma. The
      present report describes a patient shown to have only 8 to 9 percent factor VIII
      activity at age 30 years. The presentation of recurrent mild hemoptysis with
      upper respiratory tract infections is unusual and of interest in the differential
      diagnosis of hemoptysis.

PMID- 8131488
TI  - Left ventricular outflow tract obstruction following repair of pneumococcal
      mitral annular abscess.
AB  - An unusual case of a mitral annular abscess caused by Streptococcus pneumoniae
      was diagnosed by transesophageal echocardiography. The patient underwent surgical
      resection of the abscess and developed outflow tract obstruction. This is an
      unusual complication of the surgical procedure. The outflow tract obstruction may
      have been due to anterior displacement of the mitral valve by the abscess.

PMID- 8131489
TI  - Giant esophageal varices. An unusual cause of a posterior mediastinal mass.
AB  - Esophageal pathology rarely presents as posterior mediastinal abnormalities on
      chest roentgenograms, with the most common being hiatal hernia. We describe a
      patient with giant esophageal varices manifesting as a retrocardiac, posterior
      mediastinal mass.

PMID- 8131490
TI  - Right upper lobe pulmonary edema caused by acute mitral regurgitation. Diagnosis
      by transesophageal echocardiography.
AB  - Unilateral pulmonary edema is a distinctly unusual clinical entity, often
      misdiagnosed initially as one of the more common causes of focal lung disease.
      Predominantly lobar pulmonary edema is rarer still. We report a case of right
      upper lobe pulmonary edema caused by the acute onset of severe mitral
      regurgitation. In addition, we briefly review the other causes of unilateral
      pulmonary edema, focusing on the cases that have been reported in association
      with heart failure and valvular heart disease. The majority of cases of right
      upper lobe pulmonary edema have been associated with mitral regurgitation. In
      addition to confirming the presence of mitral regurgitation, transesophageal
      echocardiography proved useful in delineating the mechanism for edema formation.
      It detected differential gradients between the right and left pulmonary venous
      systems and documented the direction of the regurgitant flow.

PMID- 8131491
TI  - Fatal obstruction of the left ventricular outflow tract caused by low-profile
      bioprostheses in the mitral valve position.
AB  - Two cases of fatal left ventricular outflow tract obstruction following mitral
      valve replacement with low-profile bioprostheses are described. This unfortunate
      experience shows that correct orientation of the prosthesis is mandatory also
      when using low-profile bioprosthetic valves to avoid this complication,
      particularly in patients with a small left ventricular cavity.

PMID- 8131492
TI  - Minoxidil overdose.
AB  - A 52-year-old man ingested 60 ml of 2 percent topical minoxidil solution
      resulting in severe hypotension and tachycardia. He was resuscitated with
      intravenously administered crystalloid solution and treated with intravenously
      administered dopamine, resulting in a partial hemodynamic improvement. Further
      treatment with intravenously administered phenylephrine infusion resulted in
      resolution of hypotension. The patient suffered a non-Q-wave myocardial
      infarction as a result of the ingestion. The toxicity of this increasingly common
      preparation is profound.

PMID- 8131493
TI  - Pulmonary sequestration with primary blastomycosis. Failure of ketoconazole
      therapy after resection.
AB  - Infection with Blastomyces dermatitidis developed in a girl with occult pulmonary
      sequestration. Six months after resection, while receiving ketoconazole, she
      developed an abscess due to B dermatitidis over the scar from thoracotomy, with a
      sinus tract to the eighth rib. This was successfully managed with debridement,
      rib resection, and amphotericin B. Contiguous bone involvement should be
      suspected in sequestra infected with this organism; debridement and therapy with
      amphotericin B might be indicated.

PMID- 8131494
TI  - Pulmonary embolization and infarction. An iatrogenic complication of
      transcatheter embolization of a cerebral arteriovenous malformation with
      polyvinyl alcohol sponge.
AB  - Transcatheter embolization therapy of vascular abnormalities is a well-accepted
      technique. It is particularly useful in the preoperative management of cerebral
      arteriovenous malformations, in which the risk of significant hemorrhage at
      surgery would otherwise be unacceptably high. A patient developed symptomatic
      pulmonary emboli and infarction following an uneventful embolization using
      polyvinyl alcohol particles. The authors believe this to be the first reported
      case of this complication of embolic therapy using polyvinyl alcohol.

PMID- 8131495
TI  - Lung carcinoma in a patient with Lucite sphere plombage thoracoplasty.
AB  - A patient with a history of pulmonary tuberculosis was treated in 1949 with
      Lucite sphere plombage thoracoplasty. She subsequently developed squamous cell
      carcinoma of the lung despite having no history of exposure to known carcinogens
      associated with the development of squamous cell carcinoma. The patient's lung
      carcinoma developed adjacent to the plombage space. Lung carcinoma has not
      previously been reported in association with Lucite sphere plombage.

PMID- 8131496
TI  - A life-threatening tracheal localization of lymphoma in a patient with AIDS.
AB  - Lymphoma is a frequent complication of HIV infection, but we report a rare
      localization in the subglottic tracheal area. A case of tracheal stenosis due to
      lymphoma in an HIV-infected patient is presented. The main complaint was severe
      dyspnea. Chemotherapy was ineffective but radiotherapy improved the patient's
      condition and increased the caliber of the tracheal lumen.

PMID- 8131497
TI  - Adenosine-induced torsades de pointes.
AB  - Physicians are finding increased applications for adenosine as a diagnostic and
      therapeutic modality for a variety of cardiac dysrhythmias. Its short half life
      and lack of reported major complications make it an ideal pharmacologic agent to
      utilize for diagnosis and treatment. Herein we report a case of polymorphic
      ventricular tachycardia induced by adenosine.

PMID- 8131498
TI  - Treatment of pulmonary aspergilloma by endoscopic intracavitary instillation of
      ketoconazole.
AB  - The authors report a case of pulmonary aspergilloma in which a fungus ball was
      visualized and a biopsy specimen was obtained at fiberoptic bronchoscopy. The
      fungus ball was successfully treated with bronchoscopic instillation of
      ketoconazole. It appears that this approach can be useful in the treatment of
      patients who are high-risk candidates for pulmonary resection.

PMID- 8131499
TI  - Expandable metallic stents applied to benign bronchostenosis.
AB  - Tandem Gianturco expandable metallic stents (GEMSs) with barbs were inserted to
      dilate the left main bronchus of a 38-year-old man who had developed left
      bronchostenosis due to bronchial tuberculosis. Through the use of these GEMSs,
      ventilation in the left lung remarkably improved; however, the central airway
      resistance was found to be greater than that exhibited by the normal side and the
      mucociliary transport function was reduced.

PMID- 8131500
TI  - Noninvasive face-mask mechanical ventilation in patients with acute hypercapnic
      respiratory failure.

PMID- 8131501
TI  - Training and competence in bronchoscopy. The thoracic surgeon's viewpoint.

PMID- 8131502
TI  - Utilization of the peak expiratory flow rate in evaluation of acute dyspnea of
      cardiac or pulmonary origin.

PMID- 8131503
TI  - Methotrexate and asthma.

PMID- 8131504
TI  - New forceps for biopsy of peripheral airways.

PMID- 8131505
TI  - Reduced mortality rates in severe adult respiratory distress syndrome.

PMID- 8131506
TI  - Giant T-wave inversion in patients with acute coronary insufficiency.

PMID- 8131507
TI  - Pneumothorax complicating BiPAP therapy for Pneumocystis carinii pneumonia.

PMID- 8131508
TI  - Ventilation-perfusion inequalities in a patient with obliterative bronchiolitis
      after single-lung transplantation for primary pulmonary hypertension.

PMID- 8131509
TI  - Elevation of cardiac output and oxygen delivery improves outcome in septic shock.

PMID- 8131510
TI  - Elevation of cardiac output and oxygen delivery improves outcome in septic shock.

PMID- 8131511
TI  - Asthma, lymphocytes, and dendritic cells.

PMID- 8131512
TI  - Cardiovascular alterations in heat stroke.

PMID- 8131513
TI  - Mast cells in fibrotic lung disorders.
AB  - Fibrotic lung disorders are chronic inflammatory diseases in which inflammatory
      processes in the lower respiratory tract injure the lung and modulate the
      proliferation of mesenchymal cells that form the basis of the fibrotic scar. The
      pathogenesis of fibrosis in fibrotic lung disorders remains unclear; however,
      recent attention has focused on the potential role of the mast cell in the
      genesis of fibrosis. To determine whether mast cells are implicated in the
      pathogenesis of lung fibrosis, mast cells were compared with the degree of
      fibrosis in transbronchial lung biopsy specimens from 49 patients with fibrotic
      lung disorders (16 sarcoidosis, 15 farmer's lung disease, 9 cryptogenic fibrosing
      alveolitis, 6 bronchiolitis obliterans organizing pneumonia, 3 histiocytosis X).
      In lung tissue of patients with fibrotic lung disorders, there was an increased
      number of mast cells in respect to the control group (98.6 +/- 7.7 vs 27.8 +/-
      5.1 mast cells per square millimeter, p < 0.01). Mast cell counts in lung biopsy
      specimens were significantly correlated with the degree of fibrosis (r = 0.87, p
      < 0.001); 80.8 percent of mast cells were found in the alveolar septa, 9.6
      percent within alveoli, 1.9 percent among alveolar lining cells, and 5 percent
      along blood vessels. No mast cells were located within alveoli in controls. Our
      data suggest that mast cells participate in chronic inflammation and that their
      presence is related to interstitial fibrosis in a much broader spectrum of
      fibrotic lung disorders.

PMID- 8131515
TI  - What is "guarded condition" anyway?

PMID- 8131514
TI  - Intraepithelial dendritic cells and selective activation of Th2-like lymphocytes
      in patients with atopic asthma.
AB  - This study examines the distribution of intraepithelial dendritic cells in eight
      atopic patients with symptomatic asthma and their ability to induce activation of
      autologous T lymphocytes in vitro. All subjects were sensitized to
      Dermatophagoides pteronyssinus. The incubation of asthmatic epithelial cells and
      dendritic cells with autologous resting CD4-positive T cells and purified
      extracts of D pteronyssinus induced T cell activation and release of high levels
      of interleukin-4 (IL-4) and interleukin-5 (IL-5). The antigen-presenting activity
      of dendritic cells was potentiated by epithelial cell-derived granulocyte
      macrophage colony-stimulating factor (GM-CSF), since an antibody against GM-CSF
      reduced it. Circulating monocytes of the two groups of donors were equally
      effective in promoting selective activation of IL-4- and IL-5-producing T cells.
      Thus, an interaction between dendritic cells and allergens may favor local
      activation of CD4-positive T cells with Th2-like function in atopic asthmatic
      subjects, thereby promoting the expression of the disease.

PMID- 8131516
TI  - Perspectives on methotrexate in the treatment of asthma.

PMID- 8131517
TI  - Diagnosis of Pneumocystis carinii pneumonia. How invasive?

PMID- 8131518
TI  - High-frequency ventilation in acute pediatric respiratory failure.

PMID- 8131519
TI  - Angina pectoris caused by pernicious anemia.

PMID- 8131520
TI  - Assessment of operative risk in patients undergoing lung resection. Importance of
      predicted pulmonary function.

PMID- 8131521
TI  - Pulmonary involvement in the hypereosinophilic syndrome.
AB  - Hypereosinophilic syndrome (HES) is an infiltrative disease of eosinophils
      affecting multiple organs, including the lung. Hypereosinophilic syndrome differs
      from acute and chronic eosinophilic pneumonia clinically and usually necessitates
      treatment with alkylating agents and/or corticosteroids. We describe two patients
      with HES and pulmonary involvement. One of our patients developed the adult
      respiratory distress syndrome thought to be a complication of the HES. Aggressive
      treatment of HES in both cases combined with intensive support in the patient
      with ARDS resulted in prolonged survival.

PMID- 8131522
TI  - Normal range of methacholine responsiveness in relation to prechallenge pulmonary
      function. The Normative Aging Study.
AB  - Methacholine airway responsiveness has been observed to be related to
      prechallenge level of pulmonary function; however, normal ranges of
      responsiveness for specific levels of lung function have not been reported. We
      examined methacholine airway responsiveness in relation to level of prechallenge
      pulmonary function in a sample of 547 middle-aged and elderly men who denied any
      history of respiratory illness or symptoms and who had normal levels of
      prechallenge FEV1 and FEV1/FVC ratio. The cumulative dose of methacholine
      provoking a 20 percent decline in FEV1 (PD20FEV1) was positively correlated with
      prechallenge FEV1 percent predicted (Spearman correlation r = 0.35, p < 0.0001).
      The fifth percentile of PD20FEV1, chosen as an estimate of the lower limit of the
      normal range, varied with the level of prechallenge FEV1. When applied to a
      larger sample of 838 men with normal pulmonary function, the use of FEV1-specific
      cut-off values to separate "normal" from "abnormal" PD20FEV1 did not improve the
      sensitivity or specificity of methacholine challenge as a test for questionnaire
      reported asthma or wheezing. These data provide lower limits of normal PD20FEV1
      which are specific for a subject's prechallenge FEV1; however, these FEV1
      specific lower limits of normal PD20FEV1 provided no greater sensitivity and
      specificity for detecting asthma and wheezing than did a single lower limit of
      normal PD20FEV1 for all subjects.

PMID- 8131523
TI  - Eucapnic voluntary hyperventilation as a bronchoprovocation technique. Comparison
      with methacholine inhalation in asthmatics.
AB  - Methacholine inhalation challenge (MIC) is probably the most widely used and best
      standardized test for nonspecific bronchoprovocation challenge (BPC). There has
      been increasing interest in developing "physical" stimuli such as eucapnic
      voluntary hyperventilation (EVH) with dry gas to assess airway hyperreactivity
      (AHR), because of inherent problems with using a pharmacologic agent in
      epidemiologic surveys. To our knowledge, no studies exist that compare MIC with
      EVH in known asthmatics. We conducted a prospective, randomized, crossover trial
      with a group of subjects (n = 16) who met the American Thoracic Society
      definition of asthma with these objectives: (1) to compare the sensitivity of EVH
      with MIC; (2) to compare the quantitative response of one test with the response
      to the other challenge; and (3) to correlate the response of both tests with
      symptoms, serum IgE levels, and serum eosinophil counts. We found that (1) EVH
      was positive in 75 percent of cases and MIC was positive in 81 percent of cases;
      one subject reacted to EVH but not to MIC and vice-versa. (2) The quantitative
      response to one test correlated with the response to the other test (r = -0.60, p
      = 0.01). (3) There was a correlation between severity of asthma symptoms and the
      response to EVH (r = 0.62; p = 0.01), but not to MIC. (4) Response to MIC (log
      PD20), but not EVH, correlated with serum IgE level (r = -0.53, p = 0.04). We
      suggest that EVH may be used for the initial assessment of AHR in the evaluation
      of asthma. Eucapnic voluntary hyperventilation is a sensitive measure of AHR and
      it correlates well with symptoms. Furthermore, though these points were not
      addressed in our study, it is more physiologic than MIC, and it is easy and less
      expensive to perform.

PMID- 8131524
TI  - Acute effect of sodium cromoglycate on airway narrowing induced by 4.5 percent
      saline aerosol. Outcome before and during treatment with aerosol corticosteroids
      in patients with asthma.
AB  - STUDY OBJECTIVE: To investigate the acute effect of sodium cromoglycate on airway
      responses to 4.5 percent saline aerosol challenge, before and during treatment
      with inhaled budesonide--a corticosteroid. DESIGN: Open study, with a total of
      five visits, two before budesonide treatment, and three follow-up visits, two
      between 5 and 6 weeks and one at more than 11 weeks. SETTING: Referral-based
      Respiratory Investigation Unit at Royal Prince Alfred Hospital, a major Sydney
      based teaching hospital. PATIENTS: Eleven patients with asthma (ten atopic), with
      a PD20 FEV1 to 4.5 percent saline aerosol challenge and about to commence inhaled
      budesonide for treatment of their asthma. INTERVENTIONS: The 40 mg of sodium
      cromoglycate was inhaled before a 4.5 percent NaCl challenge, both before and
      after regular (36 +/- 9 d) treatment with budesonide (1,000 micrograms/d). The
      final challenge was repeated in ten subjects after 11 weeks or more of treatment
      with budesonide. MEASUREMENTS AND RESULTS: Sensitivity to 4.5 percent saline
      aerosol was measured as the dose of saline aerosol required to induce a 20
      percent fall in FEV1 (PD20). Reactivity was measured as the dose-response slope
      by taking the percent fall in FEV1 and dividing it by the dose required to induce
      the fall. On the control day the geometric mean PD20 (95 percent CI) for 4.5
      percent saline aerosol was 2.8 (1.4 to 5.4) and the dose response slope (DRS) 5.6
      (2.9-11.1). An acute dose of sodium cromoglycate reduced sensitivity (PD20) by 8
      fold and reactivity (DRS) 12.3-fold. This effect was similar in magnitude to that
      measured after regular treatment with budesonide alone. When sodium cromoglycate
      was given during treatment with budesonide, the PD20 was reduced 16-fold and the
      DRS 42-fold, and this was greater than the reduction with budesonide taken for 3
      months (p < 0.03, p < 0.05 respectively). CONCLUSIONS: Sodium cromoglycate
      inhibits responses to 4.5 percent saline aerosol and has additional benefits to
      those conferred by aerosol steroids. The mechanism for responsiveness to saline
      aerosol and efficacy of these drugs may relate to alteration in chloride ion
      channel regulation by inflammation.

PMID- 8131525
TI  - Serum levels of soluble IL-2R, IL-4, and soluble Fc epsilon RII in adult
      bronchial asthma.
AB  - Examination was made of the serum levels of interleukin 4 (IL-4), soluble Fc
      epsilon RII (sFc epsilon RII), and soluble interleukin 2 receptor (sIL-2R) in 77
      adult patients with bronchial asthma. All the patients had mild to moderate
      asthma and their symptoms were well controlled. The results were compared with
      values for 75 control subjects to clarify the involvement of these factors in the
      pathogenesis of bronchial asthma. Serum sIL-2R was elevated in asthmatics
      compared with control subjects (459.0 +/- 30.4 U/ml vs 251.5 +/- 10.0 U/ml; p <
      0.001). The IL-4 and sFc epsilon RII levels were also elevated beyond those in
      the controls (IL-4: 1.89 +/- 0.13 pg/ml vs 1.08 +/- 0.15 pg/ml; p < 0.001) (sFc
      epsilon RII: 313.2 +/- 18.8 U/ml vs 228.8 +/- 6.7 U/ml, p < 0.001). A weak but
      significant correlation was observed between sIL-2R and sFc epsilon RII (r =
      0.46, p < 0.001). Correlation among other parameters was not found. The patients
      were divided into atopic and nonatopic groups, based on the presence or absence
      of positive reaction to skin prick tests using extracts of common aeroallergens
      and positive specific IgE against house dust mite (Dermatophagoides pteronyssinus
      [Dp]). Mean IL-4 in the atopic group, with positive skin reaction and > 0.7 kU/L
      specific IgE against Dp was significantly elevated compared with the nonatopic
      group (2.35 +/- 0.26 pg/ml vs 1.56 +/- 0.12 pg/ml; p < 0.005). Such differences
      could not be detected in sIL-2R, sFc epsilon RII levels among the two groups. No
      significant correlation could be found among IL-4, sFc epsilon RII, and total IgE
      level. The activation of T cells and B cells would thus appear essential to the
      pathogenesis of bronchial asthma and the hypothesis that atopic status is
      associated with the preferential activation of TH2 cells which selectively
      produce IL-4 could be supported. The regulatory mechanism of IgE synthesis would
      not appear to be the only responsible factor.

PMID- 8131526
TI  - Detection of cytokines and their cell sources in bronchial biopsy specimens from
      asthmatic patients. Relationship to atopic status, symptoms, and level of airway
      hyperresponsiveness.
AB  - This study evaluated immunoreactivity for several cytokines in bronchial tissue
      of asthmatic patients and related this to the clinical and functional
      characteristics. Patients were allocated into two different groups on the basis
      of their atopic status (atopic and nonatopic), with two subgroups of symptomatic
      and asymptomatic subjects in each. Five healthy volunteers were tested as control
      subjects. After clinical and functional assessment, all of the subjects underwent
      bronchoscopy. Several biopsy specimens were obtained for immunohistochemical and
      immunoelectron microscopic evaluation. Symptomatic asthmatic subjects had
      increased expression of immunoreactive interleukin (IL) 1 beta, IL-2, IL-3, IL-5,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis
      factor alpha (TNF alpha) when compared to the asymptomatic patients or normal
      control subjects. The cell sources of IL-1 beta were monocytes and dendritic
      cells in atopic patients and monocytes alone in nonatopic asthmatic subjects. The
      CD4+ T lymphocytes from atopic asthmatic subjects predominantly expressed IL-3,
      IL-4, IL-5, and GM-CSF immunoreactivity, whereas CD4+ T cells from nonatopic
      patients predominantly expressed IL-2, IL-3, and IL-5, and GM-CSF
      immunoreactivity. Mast cells showed immunoreactivity for TNF alpha, IL-3, IL-5,
      and GM-CSF. Immunostaining for TNF alpha and GM-CSF was also detected in
      bronchial epithelial cells and monocytes. Tissue eosinophilia and the level of
      airway hyperresponsiveness more closely correlated with IL-5 immunoreactivity in
      atopic asthmatic subjects and with IL-2 and GM-CSF immunoreactivity in nonatopic
      patients.

PMID- 8131527
TI  - Bronchodilating effect of terbutaline powder in acute severe bronchial
      obstruction.
AB  - The bronchodilating effect of terbutaline dry powder inhaled via Turbuhaler was
      compared with terbutaline inhaled via a conventional, chlorofluorocarbon (CFC)
      inhaler and Nebuhaler (750 ml spacer) in 68 consecutive patients attending the
      emergency department with acute severe bronchial obstruction. The study was of an
      open, randomized, parallel group design with one study day. Patients were treated
      with 2.5 mg of terbutaline 15 min apart, either as dry powder via Turbuhaler or
      with a CFC inhaler in conjunction with Nebuhaler. Data from 62 patients were
      analyzed. The mean baseline FEV1 values were 0.81 L (SD, 0.64; range, 0.14 to
      2.74 L) in the Turbuhaler group (n = 33), and 0.90 L (SD, 0.90; range, 0.27 to
      2.60 L) in the Nebuhaler group (n = 29). The mean increases in FEV1 from baseline
      were 0.40 L (SD, 0.40; range, 0.06 to 2.36 L) and 0.21 L (SD, 0.25; range, -0.05
      to 0.95 L) 10 min after the last inhalation via Turbuhaler and Nebuhaler,
      respectively. The difference between mean values of the increase in FEV1 after
      terbutaline treatment with Turbuhaler and the CFC inhaler and Nebuhaler was
      statistically significant (p = 0.0004, ANOVA). This study showed that inhalation
      of terbutaline via Turbuhaler produced a significantly greater increase in FEV1
      compared with the same dose of terbutaline administered via the CFC inhaler and
      Nebuhaler in patients attending the emergency department with acute severe
      bronchial obstruction.

PMID- 8131528
TI  - Magnesium sulfate potentiates several cardiovascular and metabolic actions of
      terbutaline.
AB  - beta-Adrenergic agonists are useful for the emergency treatment of asthma.
      Recently, magnesium sulfate (MgSO4) has also been shown to be efficacious in this
      situation. beta-Agonists have unwanted cardiovascular and metabolic actions:
      increased systolic blood pressure, corrected QT interval (QTc), serum glucose and
      insulin, and decreased RR interval, diastolic blood pressure, serum potassium,
      phosphate, and calcium. As beta-agonists and MgSO4 quite possibly will be used in
      combination, we sought to determine how MgSO4 would affect these actions. Healthy
      young male adults were administered two doses of terbutaline sulfate, 0.25 mg
      subcutaneously, 30 min apart on two separate occasions, in a randomized, double
      blind fashion. On one occasion, 4 g of MgSO4 was administered intravenously over
      the same 30-min period. On the other, normal saline solution was given as a
      placebo. Cardiovascular and metabolic variables were measured sequentially for 2
      h. Data at 60 min with p values given for a summation of all time points are as
      follows: MgSO4 increased terbutaline's effects on the RR interval by 0.09 s, p <
      0.0001; QTc interval by 0.01 s, p < 0.0007; diastolic blood pressure by 8 mm Hg,
      p = 0.0001; serum calcium by 0.13 mg/dl, p = 0.01; and glucose by 9 mg/dl, p <
      0.0001. MgSO4 also mitigated the systolic blood pressure elevating the effect of
      terbutaline by 5 mm Hg (p = 0.007). The magnitude of the response potentiations
      was modest. We conclude that combining terbutaline and MgSO4 is unlikely to
      result in serious short-term adverse events, if used acutely in patients with
      relatively normal cardiac and metabolic function. MgSO4 may act by potentiating
      the effect of beta-agonists on magnesium requiring enzymes such as adenyl
      cyclase.

PMID- 8131529
TI  - Airway response to a bronchodilator in healthy parents of infants with
      bronchiolitis.
AB  - In order to assess the role of genetic factors and environmental influences in
      bronchial responsiveness, we studied the airway response to an inhaled
      bronchodilator in 66 nonasthmatic parents (age, 30.9 +/- 5.9 years) of infants
      with bronchiolitis (group 1). It was a placebo-controlled double-blind study. A
      control group (group 2) of healthy parents of infants who did not have
      bronchiolitis also were investigated with the test of bronchodilator response.
      All subjects showed normal expiratory airflow and lung volumes (forced vital
      capacity [FVC], forced expiratory volume in 1 s [FEV1], and mean forced
      expiratory flow during the middle half of FVC [FEF25-75%] > 80 percent of
      predicted) at baseline forced expiratory maneuver. In 16 (24.2 percent) subjects
      of group 1, there was significant increase in at least one parameter after
      salbutamol administration, but not after placebo inhalation, with respect to
      baseline levels. Furthermore, no significant changes in FVC, FEV1, or FEF25-75%
      values were found in group 2. In conclusion, this study confirms that parents of
      infants with bronchiolitis have an enhanced airway responsiveness, greater than
      control parents. Further studies are needed to assess whether one may infer the
      outcome of infants with bronchiolitis from this characteristic in their parents.

PMID- 8131530
TI  - Assessment of interrater and intrarater reliability in the evaluation of metered
      dose inhaler technique.
AB  - STUDY OBJECTIVE: To determine if a training session using videotaped metered dose
      inhaler (MDI) performances can result in high interrater and intrarater
      reliability of five evaluators assessing MDI technique. DESIGN: Five evaluators
      (three pharmacists, two pulmonary fellows) were trained to evaluate MDI technique
      during a 2-h training session. The training session consisted of verbal
      instruction and practical experience in evaluating MDI technique using video
      taped MDI performances of six nonstudy subjects. After the training session, the
      evaluators independently observed the same videotaped MDI demonstrations of 14
      subjects on two occasions separated by a 7- to 10-day interval. Interrater and
      intrarater reliability was determined for individual steps by calculating percent
      agreement and intraclass correlation (ICC) coefficient. RESULTS: Interrater. The
      interrater reliability for individual steps ranged from 29 to 86 percent (ICC
      coefficient = 0.13 to 0.81). Steps in which evaluators were in agreement for less
      than 9 of the 14 subjects were shaking the inhaler before inhalation, exhaling,
      continuing to inhale slowly, and adequate breath hold. Intrarater: The overall
      percent agreement by step ranged from 74 to 97 percent. Exhaling to functional
      residual volume (76 percent) and continuing to inhale slowly and deeply (74
      percent) had the lowest overall agreement between the first and second
      observation day. The consistency of evaluating a step between the two observation
      days varied considerably depending on the step and evaluator. CONCLUSIONS: High
      interrater and intrarater reliability in MDI evaluation is difficult to obtain.
      Clinicians and researchers involved in MDI evaluation and education should be
      trained to achieve consistency. A single training session using videotaped MDI
      demonstrations was not adequate in achieving consistency among evaluators. To
      improve accuracy of research results, researchers should include at least two
      evaluators to assess MDI technique or take other measures to show and report
      reliability.

PMID- 8131531
TI  - Misuse of metered-dose inhalers in hospitalized patients.
AB  - Metered-dose inhalers (MDIs) have been associated with a high rate of misuse.
      Medical personnel also have a poor understanding of MDI technique. Hospitalized
      patients had their MDI technique observed before and after a series of inservices
      were provided to hospital personnel on correct MDI use. The rate of misuse did
      not change with 55 of 72 (76 percent) patients making errors in the first group
      before, and 45 of 55 (82 percent) patients making errors in the second group
      after staff education (p = 0.46). The average number of errors per patient was
      2.39 in group 1 and 2.45 in group 2 (p = 0.93). Alternatives to deal with this
      high rate of MDI misuse are discussed.

PMID- 8131532
TI  - Prevention and regression of coronary atherosclerosis. Is it safe and efficacious
      therapy?
AB  - OBJECTIVE: Atherosclerotic coronary heart disease (CHD) continues to be the
      dominant disease in Western society. A large body of evidence directly linking
      serum cholesterol levels and CHD risk has stimulated population treatment
      strategies designed to reduce cholesterol and CHD risk. Data indicating a
      relation between low cholesterol and non-CHD risk have, however, suggested that
      cholesterol reduction may not always be desirable. The primary goal of this
      evaluative review of the available evidence was to answer the following question:
      Is prevention/regression therapy for CHD safe and effective? DATA SOURCES: Three
      lines of evidence were reviewed: epidemiologic studies; primary and secondary
      prevention trials with clinical end points; and secondary prevention trials with
      quantitative coronary angiography as a surrogate end point for clinical CHD.
      STUDY SELECTION: Original studies and meta-analyses were reviewed. The principal
      selection criteria for the epidemiologic studies were large size and prolonged
      follow-up; for the trials, randomization and viable clinical (CHD events, CHD
      mortality, total mortality) or angiographic end points. DATA EXTRACTION: The data
      were initially extracted by a single reviewer using common qualitative
      guidelines. The data were then evaluated by all authors acting as a data
      interpretation team. DATA SYNTHESIS: Overall, the epidemiologic data revealed
      excess risk of fatal and nonfatal CHD events was directly related to total
      cholesterol and low-density lipoprotein (LDL) cholesterol levels, for both men
      and women and for both younger (< 65 years) and older (> or = 65 years) patients,
      over a wide range of serum cholesterol levels. The predictive value was higher in
      younger men than older men and women, although part of this quantitative
      interaction may be due to fewer studies, with fewer end points, in the older and
      female populations. The CHD events and CHD mortality, but not total mortality,
      were consistently reduced in trials of cholesterol-lowering therapy. The
      regression trials, predominantly in CHD patients with high cholesterol values
      (mean 7.1 mmol/L), demonstrated improvement in angiographic atherosclerosis in
      every study. The evidence for elevated risk of non-CHD death at very low levels
      of cholesterol is uncertain and controversial. The most likely possibilities for
      this apparent relationship are unknown confounding variables and the play of
      chance. CONCLUSIONS: Serum cholesterol levels are directly associated with CHD
      risk, and there is no threshold level below which there is no risk. Reduction of
      high serum cholesterol levels reduces CHD risk. Whether lipid-lowering and
      adjunctive antiatherosclerotic therapies are effective and safe in the majority
      of CHD patients who have desirable or borderline cholesterol levels remains
      undetermined.

PMID- 8131533
TI  - Should all patients undergoing cardiac catheterization or percutaneous
      transluminal coronary angioplasty receive oxygen?
AB  - BACKGROUND: Supplemental oxygen is routinely administered to patients with acute
      coronary syndromes. The risk of significant morbidity during cardiac
      catheterization or coronary angioplasty has been well described; however, to our
      knowledge, the need for routine oxygen supplementation in these patients has not
      been investigated. METHODS: In phase 1, we prospectively studied 142 patients
      undergoing diagnostic cardiac catheterization (n = 94) or percutaneous
      transluminal coronary angioplasty (PTCA) (n = 48) to determine the incidence of
      procedure-related hypoxemia (pulse oximetry derived oxygen saturation [SpO2] < 90
      percent of > 1 min duration) while breathing room air (RA). In phase 2, 134
      patients undergoing diagnostic cardiac catheterization (n = 78) or PTCA (n = 56)
      were randomly allocated to breathe either RA or supplemental oxygen (O2, 6 L/min
      by nasal cannula) to determine the effect of oxygen administration on procedure
      related hypoxemia. Oximetry results were compared with pertinent clinical and
      procedural data that might predispose patients to develop hypoxemia. RESULTS:
      Phase 1--Moderate to severe hypoxemia occurred in 36 percent (34/94) of patients
      undergoing diagnostic catheterization and in 56 percent (27/48) of patients
      undergoing PTCA. In the diagnostic catheterization group, there were a total of
      25 episodes of moderate hypoxemia (SpO2 85 to 89 percent) lasting 4.0 +/- 4.3 min
      and 11 episodes of severe hypoxemia (SpO2 < 85 percent) of greater duration, 11.7
      +/- 7.5 min (p < 0.008). In the PTCA group, there were 24 episodes of moderate
      hypoxemia and six episodes of severe hypoxemia lasting 4.8 +/- 4.3 min and 8.2 +/
      3.8 min, respectively. A history of chronic lung disease was associated with
      hypoxemia (p < 0.05) in the diagnostic group. In addition, 11 patients undergoing
      diagnostic catheterization who had baseline SpO2 < 95 percent all developed
      hypoxemia during the procedure. In this subset of patients, there was a higher
      incidence of cigarette smoking (p = 0.02), chronic lung disease (p = 0.04),
      higher left ventricular diastolic pressure (p = 0.02), and lower ejection
      fraction (p = 0.002) when compared with the 83 remaining patients undergoing
      diagnostic catheterization with a baseline SpO2 > 95 percent. Phase 2--Oxygen
      therapy was associated with a reduction in the incidence of hypoxemia from 42
      percent to 5 percent (RA vs O2, p < 0.001) in the diagnostic catheterization
      group and 39 percent to 11 percent (RA vs O2, p < 0.03) in the PTCA group.
      CONCLUSIONS: Significant hypoxemia is a common finding among patients undergoing
      cardiac catheterization or angioplasty despite the absence of predictive risk
      factors. Severe and prolonged hypoxemic episodes occurred in 10 percent (14/142,
      phase 1) of patients breathing room air. Patients undergoing diagnostic
      catheterization with history of chronic lung disease or a baseline SpO2 < 95
      percent are at high risk to develop moderate-severe hypoxemia. Oxygen therapy
      significantly reduced the incidence and severity of procedure-induced hypoxemia
      in both groups. Our data support the use of both pulse oximetry and oxygen
      supplementation in patients undergoing cardiac catheterization and PTCA.

PMID- 8131534
TI  - Survival after percutaneous transluminal coronary angioplasty in patients with
      severe left ventricular dysfunction.
AB  - To assess the effects of coronary angioplasty in patients with severe left
      ventricular dysfunction, the results of procedures, performed between 1987 and
      1991, in 100 patients (90 male) with left ventricular function < or = 0.35
      (range, 0.20 to 0.35) and anginal symptoms were analyzed. Mean age was 62 +/- 10
      years (range, 38 to 85 years). Ninety-five patients had previous myocardial
      infarction and 27 patients had previous coronary artery bypass grafting. Unstable
      angina was present in 81 percent of patients. Single-vessel disease was present
      in 6 patients, double vessel was present in 31 patients, and triple-vessel
      disease was present in 63 patients. Percutaneous transluminal coronary
      angioplasty (PTCA) was attempted on 164 vessels, 27 of these with chronic total
      occlusion. The overall angiographic success rate was 84 percent. Myocardial
      infarction occurred in four patients, six patients underwent urgent coronary
      bypass surgery, and seven patients died of cardiac causes. There was a 9 percent
      incidence of total in hospital mortality. Major complications were significantly
      more frequent in patients with triple-vessel disease. Clinical success was
      achieved in 75 patients, 55 of these with incomplete revascularization. Long-term
      follow-up (mean, 19 +/- 7 months) was available in all patients with clinical
      success. Thirteen patients had repeated PTCA, 8 patients had coronary surgery,
      and 13 patients died. In conclusion, in patients with severe left ventricular
      dysfunction, acute complications and late mortality rate are high. Patients with
      triple-vessel disease are a higher risk subset and have no long-term benefits by
      PTCA.

PMID- 8131535
TI  - Efficacy of breathing and coughing exercises in the prevention of pulmonary
      complications after coronary artery surgery.
AB  - One hundred twenty patients undergoing coronary artery surgery completed a
      randomized controlled study designed to investigate whether prophylactic chest
      physiotherapy affected the incidence of postoperative pulmonary complications.
      Group 1 patients received no preoperative or postoperative chest physiotherapy.
      Group 2 patients received preoperative education and instruction in breathing and
      coughing exercises and postoperative supervision and assistance in performing the
      same. These exercises were supervised by a physiotherapist twice per day on the
      first 2 postoperative days and once per day on the 3rd and 4th postoperative
      days. Physiotherapy for group 3 patients was the same as for group 2 patients
      except that patients were seen by a physiotherapist 4 times per day on the first
      2 postoperative days and twice per day on the 3rd and 4th postoperative days.
      Group 2 and 3 patients were instructed to practice breathing and coughing
      exercises every hour. Overall, an incidence of clinically significant
      postoperative pulmonary complications of 7.5 percent was demonstrated. In
      general, these patients demonstrated lower levels of preoperative pulmonary
      function and very low early postoperative oxygenation compared with those who did
      not develop pulmonary complications. There was no indication that the incidence
      or severity of fever, hypoxemia, chest roentgenologic abnormalities or clinically
      significant postoperative pulmonary complications was different between groups.
      These results suggest that the necessity for prophylactic chest physiotherapy
      after routine coronary artery surgery should be reviewed.

PMID- 8131536
TI  - Clinical implications of left atrial appendage flow patterns in nonrheumatic
      atrial fibrillation.
AB  - Left atrial appendage (LAA) function and flow patterns in 29 patients with
      chronic nonrheumatic atrial fibrillation were studied by transesophageal
      echocardiography. These 29 patients (16 men and 13 women; mean age, 63.8 years;
      range, 38 to 77 years) were classified into two groups according to different LAA
      flow patterns. Seventeen patients (group 1) had well-defined LAA emptying and
      filling Doppler flow signals, and the other 12 patients (group 2) had very low
      LAA flow signals. No significant differences were found in age, sex, mean
      duration of atrial fibrillation, left ventricular end diastolic dimension, and
      left ventricular ejection fraction between the two groups. However, group 2
      patients had larger left atrial diameter (42.8 +/- 4.2 mm vs 36.6 +/- 8.8 mm; p <
      0.05), lower LAA ejection fraction (26.4 +/- 15.2 percent vs 42.6 +/- 14.1
      percent; p < 0.05), and lower LAA peak emptying velocity (0.13 +/- 0.03 m/s vs
      0.36 +/- 0.16 m/s; p < 0.001). Higher incidence of LAA spontaneous
      echocardiographic contrast formation in group 2 patients (8/12 vs 1/17; p <
      0.001) was noted. In conclusion, a subset of patients with nonrheumatic atrial
      fibrillation were found to have lower LAA blood flow and poorer LAA function.
      These patients had higher incidence of left atrial or LAA spontaneous echo
      contrast formation which had been proved previously to be a marker for future
      systemic thromboembolism.

PMID- 8131537
TI  - Assessment of operative risk in patients undergoing lung resection. Importance of
      predicted pulmonary function.
AB  - OBJECTIVE: To evaluate the ability of preoperative variables to identify patients
      at increased risk for complications after lung resection and the usefulness of
      predicted postoperative FEV1 as a marker of risk for adverse outcomes. DESIGN:
      Prospective analysis of a cohort of patients undergoing pulmonary resection.
      Complication rates were analyzed according to preoperative pulmonary variables,
      demographic variables, procedure performed, and predicted postoperative FEV1.
      Predicted postoperative FEV1 was calculated using a formula estimating the
      decline in preoperative FEV1 based on the number of bronchopulmonary segments
      removed during surgery. SETTING: A major teaching hospital and tertiary referral
      center. PATIENTS: A consecutive series of patients undergoing pulmonary
      resection. MEASUREMENTS AND MAIN RESULTS: Medical complications were recorded as
      part of an ongoing clinical database. The overall complication rate was low (17
      percent rate of any complication, 1 percent death rate). Univariate predictors of
      complications included age > or = 60, male sex, history of smoking, a
      pneumonectomy procedure, and a low predicted postoperative FEV1. Hypercarbia (>
      or = 45 mm Hg) on preoperative arterial blood gas analysis, desaturation on
      exercise oximetry (< or = 90 percent), and a preoperative FEV1 less than 1 L were
      not predictive of complications. When the effect of these variables was
      controlled for in a multivariate analysis, a low predicted postoperative FEV1
      remained the only significant independent predictor of complications. For each
      0.2 L decrease in predicted FEV1, the odds ratio for complications was 1.46 (95
      percent confidence interval [CI] 1.2 to 1.8). CONCLUSIONS: A low predicted
      postoperative FEV1 appears to be the best indicator of patients at high risk for
      complications, and it was the only significant correlate of complications when
      the effect of other potential risk factors was controlled for in a multivariate
      analysis. Pulmonary resection should not be denied on the basis of traditionally
      cited preoperative pulmonary variables, and a prediction of postoperative
      pulmonary function by a technique of simple calculation may be useful to identify
      patients at increased risk for medical complications.

PMID- 8131538
TI  - Pulmonary complications in patients undergoing thoracotomy for lung carcinoma.
AB  - One hundred three consecutive patients undergoing 106 thoracotomies for primary
      lung carcinoma were reviewed to determine factors associated with the development
      of postoperative pulmonary complications. Pulmonary complications occurred in 40
      of 104 (39 percent) patients. Minor complications occurred in 17 of 104 (16
      percent) patients and major in 23 of 104 (22 percent). There were six deaths in
      the entire series of 103 patients (6 percent), two of which were directly caused
      by a pulmonary complication and one where it was a contributing factor. Extended
      surgical resections were associated with an increased risk of complications.
      Pulmonary complications occurred in 9 of 11 (82 percent) patients undergoing
      extended resections involving chest wall resection. The use of neoadjuvant
      chemotherapy also was associated with an increase in the rate of major
      complications. Poor nutritional status as measured by a history of weight loss
      and preoperative serum albumin levels also was associated with an increased risk
      of any pulmonary complication. Cardiac complications were significantly increased
      in the group of patients having pulmonary complications. Pulmonary complications
      continue to present a major source of morbidity and mortality for patients
      undergoing thoracotomy for lung carcinoma. Determination of factors associated
      with increased risk is important in order to identify patients who might be
      predisposed to the development of these complications.

PMID- 8131539
TI  - Squamous cell carcinoma antigen (SCC Ag) in the diagnosis and prognosis of lung
      cancer.
AB  - OBJECTIVE: We have studied the usefulness of squamous cell carcinoma antigen (SCC
      Ag) in diagnosis and prognosis of lung cancer (LC). MATERIAL AND METHODS: We have
      measured the serum SCC Ag levels in 388 subjects: 69 healthy persons; 103 with
      nonmalignant lung diseases (NMLD); 24 with lung metastasis of extrapulmonary
      origin (LMEO); and 192 with LC (88, with squamous cell carcinoma [SCC] type). In
      55 with SCC, we analyzed the survival time. RESULTS: Serum SCC Ag was above 2.5
      ng/ml in 1.4 percent of healthy persons; 2.9 percent of those with NMLD; 8.3
      percent of those with LMEO; and 27.6 percent of those with LC. Such percentage
      was 47.7 percent in SCC. In this type, there were significant differences
      according to the extent of disease (61.6 percent in advanced stages, and 26.5
      percent in localized stages, p = 0.002). In the other types, the sensitivity was
      substantially lower. The initial SCC Ag has prognostic significance (p = 0.02) in
      the univariate analysis, but it loses such significance in a multivariate model,
      including the stage. CONCLUSIONS: Therefore, we do not recommend this marker in
      the clinical management of patients with LC, even it can be useful in the
      differential diagnosis if used in combination with other markers.

PMID- 8131540
TI  - Dyspnea in a patient years after severe poliomyelitis. The role of
      cardiopulmonary exercise testing.
AB  - Dyspnea after polio can occur for a variety of reasons, including neuromuscular
      disease and upper airway abnormalities resulting from prolonged intubation,
      including tracheal stenosis, tracheomalacia, and vocal cord paralysis. Routine
      studies such as spirometry and maximum voluntary ventilation (MVV) measurements
      can give similar results in these conditions. We present a 50-year-old woman who
      as a child developed poliomyelitis that required tracheostomy and negative
      pressure ventilation. Thirty-nine years later, she developed breathlessness with
      normal spirometry but decreased MVV. The flow volume loop showed flattening of
      the inspiratory and expiratory limbs, consistent with a fixed upper airway
      obstruction or neuromuscular weakness. Exercise testing with measurement of
      exercise flow volume loops and respiratory pressures was performed. The patient
      was ventilatory limited with increasing end-expiratory lung volume through
      exercise. Flow volume loops confirmed flow limitation. Respiratory pressures did
      not change after maximal exercise. Further evaluation confirmed left vocal cord
      paralysis and tracheomalacia. This patient demonstrates that the causes of
      dyspnea after poliomyelitis can be multifactorial, and that routine evaluation
      may fail to elucidate the limiting factor. In this case, exercise testing
      provided valuable insight into the limiting factor for this patient and provided
      useful data for counseling and for further management.

PMID- 8131541
TI  - Effects of positive expiratory pressure breathing during exercise in patients
      with COPD.
AB  - The effect of breathing with a positive expiratory pressure of 5 cm H2O was
      investigated in eight patients with COPD (mean [SD]FEV1 = 54 [13] percent
      predicted). Specific work of breathing (Wsp) and myoelectrical activity of the
      following respiratory muscles were measured at rest: scalene muscle, parasternal
      muscle, and abdominal muscles. Minute ventilation (VE), end-tidal CO2 (FETCO2),
      physiologic dead space ventilation (VD/VT), oxygen uptake (VO2), and carbon
      dioxide output (VCO2) were measured at rest and during an incremental bicycle
      exercise test. Dyspnea sensation during exercise was quantified using the CR10
      Borg-scale. All measurements were performed with and without positive expiratory
      pressure (PEP). During PEP breathing at rest mean (SEM) Wsp increased from 0.54
      (0.13) J/L to 1.08 (0.10) J/L. The SEM VE decreased from 12.4 (1.0) L/min to 10.5
      (1.1) L/min, and SEM VD/VT decreased from 0.39 (0.03) to 0.34 (0.03). There was a
      tendency for an increased phasic respiratory muscle activity during PEP breathing
      of all three muscles as compared with undisturbed breathing, but the changes were
      not statistically significant. During the exercise test with PEP, VE, VD/VT, VO2,
      and VCO2 were significantly lower, and FETCO2 was significantly higher as
      compared with the values obtained during the exercise test with undisturbed
      breathing. Dyspnea sensation during the exercise test with PEP, however, was
      higher than during the test with undisturbed breathing. The PEP breathing at rest
      may be useful in patients with COPD as it increases the efficiency of ventilation
      by reducing dead space ventilation. This beneficial effect also occurs during
      exercise, but here it is accompanied by increased dyspnea sensation.

PMID- 8131542
TI  - Oxygen consumption of respiratory muscles in patients with COPD.
AB  - We measured the oxygen consumption (VO2) of respiratory muscles in 8 COPD
      patients and 12 age-matched healthy subjects using a closed circuit device which
      allows a continuous increase in external dead space and is equipped with a 9-L
      Collins spirometer. Furthermore, we measured simultaneously mouth occlusion
      pressure at 0.1 s of inspiration (P0.1), minute ventilation (VE), and other
      ventilatory parameters during the measurement of total VO2 (VO2 tot). We found
      that the logarithm of VO2tot (logVO2tot) had a good correlation with VE in both
      groups. The mean slope of the regression line of logVO2tot and VE (delta
      logVO2tot/delta VE) of COPD patients was significantly higher than that of normal
      subjects (p < 0.001). However, the mean Y-intercept (metabolic VO2[VO2met]) of
      the regression lines did not differ between the two groups. The P0.1 in COPD
      patients was higher than that in normal subjects at the corresponding dead space
      loading. However, the VE did not differ between the two groups except for at rest
      and the first 1 min after dead space loading. These results suggest that the VO2
      of respiratory muscles in patients with COPD is higher at given ventilation
      compared with that in age-matched normal subjects and that this increased VO2
      partly may be due to an augmented ventilatory drive.

PMID- 8131543
TI  - Pulmonary vascular resistance in emphysema.
AB  - To assess the hemodynamic effects of pulmonary microvasculature disruption in
      emphysema, we examined resting pulmonary hemodynamics and lung function in 12
      carefully identified patients with type A chronic obstructive pulmonary disease.
      Individuals with respiratory muscle weakness and intercurrent infection were
      excluded. Standard spirometry, helium dilution lung volumes, and single-breath
      carbon monoxide diffusing capacity (DCOSB) were obtained within 24 h of right
      heart catheterization. Resistance to pulmonary blood flow was assessed using the
      difference between pulmonary arterial (PA) diastolic and mean wedge pressures,
      and expressed as the pulmonary diastolic gradient (PDG). Mean FEV1/FVC was 51 +/-
      8 percent, RV/TLC was 48 +/- 11 percent, DCOSB percent predicted was 62 +/- 29
      percent, PaO2 was 72 +/- 11 mm Hg (FIO2, 0.21), and PaCO2 was 39 +/- 5 mm Hg.
      Mean PDG was 5 +/- 3 mm Hg (normal < or = 3 mm Hg) with normal PA pressures,
      indicating mildly elevated resistance to pulmonary blood flow. The PDG correlated
      most closely with DCOSB, rising in curvilinear fashion as DCOSB fell (r = -0.869,
      p < 0.001). These observations were compared with our previous report of
      analogous findings in patients with chronic, diffuse interstitial lung disease
      (ILD). In that group, PDG also increased curvilinearly as DCOSB fell (r = -0.839,
      p < 0.001). Subjects with FVC greater than 50 percent predicted had elevated PDG
      with normal pressures, while those with FVC less than 50 percent had pulmonary
      hypertension. The regression of PDG on DCOSB was strikingly similar to emphysema,
      although the slope in emphysema was less than that in ILD (p < 0.001). These
      observations suggest that elevated pulmonary vascular resistance in emphysema
      stems from disruption of the microcirculation in a fashion similar to that
      encountered in mild-moderate ILD. However, the magnitude of increase is not
      sufficient to generate resting pulmonary hypertension in the absence of disturbed
      gas exchange.

PMID- 8131544
TI  - Macrophage activation by N-acetyl-cysteine in COPD patients.
AB  - The effect of in vivo and in vitro N-acetylcysteine (NAC) treatment on
      destructive activity of macrophages against Candida from COPD patients has been
      evaluated. Patients received NAC (600 mg) or placebo orally 3 times a day for 15
      days and bronchoalveolar lavage (BAL) fluid and peripheral blood were collected
      before and at the conclusion of treatment. In our system, NAC treatment was not
      able to modulate antifungal activity of alveolar macrophages, peripheral blood
      monocytes (PBM), and polymorphonuclear leukocytes. On the contrary, in vitro NAC
      treatment at appropriate doses (10 micrograms/ml) significantly enhanced
      antifungal activity of PBM from COPD patients. This phenomenon is mediated by
      augmented phagocytic activity and phagosome-lysosome fusion. The lack of
      correlation between in vivo and in vitro studies could be ascribed to differences
      in the intracellular concentration of the drug that in vivo does not reach levels
      capable of inducing macrophage activation. We speculate that in COPD patients who
      undergo long-term NAC treatment, appropriate schedules and doses of the drug
      could augment resistance against microbial infections which are often life
      threatening in these patients.

PMID- 8131545
TI  - Outbreak of Chlamydia pneumoniae infection in former injection-drug users.
AB  - In a retrospective analysis of lower respiratory tract infections in an ex
      injection-drug users community, we found an outbreak (April to July 1991) of
      Chlamydia pneumoniae infection. The epidemic occurred in a group of 26 community
      members (23 men and 3 women, mean age, 28.9--3 years) living and working
      together, who underwent acute and convalescent serologic tests for Mycoplasma
      pneumoniae, Legionella pneumophila, cytomegalovirus, adenovirus, Coxiella
      burnetii, and Chlamydia pneumoniae. All subjects were submitted to chest
      radiograph, while sputum and blood cultures were performed in symptomatic
      patients. Antibodies to C pneumoniae were determined by a microimmunofluorescence
      test. Among all subjects studied (13 HIV-1 positive and 13 HIV-1 negative), 11 (8
      HIV-positive and 3 HIV-negative) developed pneumonia, 2 (1 HIV-positive and 1 HIV
      negative) developed pharyngitis, and 2 (1 HIV- positive and 1 HIV-negative)
      developed flu-like syndromes sustained by C pneumoniae; in 4 subjects (2 HIV
      positive and 2 HIV-negative) suffering from flu-like syndrome, no causal agents
      were found. Seven subjects (one HIV-positive and six HIV- negative) remained
      asymptomatic without any evidence of infection. The prevalence of antibodies to C
      pneumoniae in HIV-1-positive subjects observed in a sample of community members
      was significantly higher than in HIV-1-negative subjects. C pneumoniae seems to
      be involved in respiratory tract infections in HIV-1-infected subjects. Our data
      suggest that C pneumoniae should be included in the diagnostic approach of
      respiratory infections in HIV-infected subjects.

PMID- 8131546
TI  - Sputum induction compared with bronchoalveolar lavage by Ballard catheter to
      diagnose Pneumocystis carinii pneumonia.
AB  - Specimens from sputum induction (SI) are often of insufficient volume or have
      poor diagnostic yield for the diagnosis of Pneumocystis carinii pneumonia (PCP).
      The Ballard catheter for bronchoalveolar lavage (BAL) is a disposable BAL device
      which is passed transnasally into the airway and wedged by sensation. Thirty
      consecutive episodes (21 inpatient and 9 outpatient) in 28 patients positive for
      HIV (15 with AIDS) were studied with SI and BAL at a tertiary-care university
      hospital. Six SIs yielded no specimen, and six were judged inadequate for
      investigation by the laboratory. The BAL return averaged 53 ml (range, 10 to 77
      ml), and all specimens were excellent quality based on microscopy. Of the 10
      patients (33 percent) who were PCP-positive on BAL, only 2 (6.9 percent) were
      detected by SI (McNemar p = 0.0078). Of 12 patients in whom SI was unobtainable
      or inadequate, 6 were positive for PCP on BAL. Two adequate specimens from SI
      were negative, but BAL specimens were positive for PCP. No patients had specimens
      that were positive for PCP on SI who had negative BAL specimens. The adequacy of
      the specimen and the PCP diagnosis with BAL were statistically superior to SI
      (McNemar p = 0.007). The Ballard BAL catheter allows easy transnasal access to
      the airway and safe BAL, with a statistically significant superior yield of
      specimens when compared to SI.

PMID- 8131547
TI  - Clinical and epidemiologic investigations of nosocomial pulmonary infections
      caused by methicillin-resistant Staphylococcus aureus.
AB  - We evaluated the clinical features of 32 patients with pulmonary infections
      caused by methicillin-resistant Staphylococcus aureus (MRSA). Most of the
      patients were elderly, postoperative, and had severe underlying diseases. Chest
      radiograph typically showed bilateral and multilobar involvement. Empyema was not
      common and no abscess was identified. Mortality rate was 38 percent. We also
      performed an epidemiologic study of MRSA infections by chromosomal DNA analysis
      using pulsed-field gel electrophoresis. Thirty-two strains were classified into
      20 different types by chromosomal DNA pattern, and 5 epidemic strains were
      observed. These strains were considered to be transmitted among patients by
      hospital personnel.

PMID- 8131548
TI  - Early aggressive surgical management of parapneumonic empyemas.
AB  - We have analyzed our experience with 90 consecutive patients who were operated on
      for parapneumonic empyema between 1981 and 1992. Patients whose empyema did not
      resolve with chest tube drainage were taken to the operating room. Nineteen
      patients had limited thoracotomy and drainage. Seventy-one patients had formal
      thoracotomy, debridement, pleurectomy, and decortication. We found that an age
      greater than 60 years, cardiac disease, end-stage renal disease, end-stage
      bronchitis, prolonged tube drainage, and immunosuppression are associated with
      increased morbidity and mortality. In those patients who do not respond well to a
      short course of chest tube drainage, we recommend early aggressive surgical
      approach, including formal thoracotomy and definitive treatment. This allowed for
      early discharge from the hospital without chest tubes or open draining wounds. In
      extremely ill patients, limited thoracotomy may be all that is safe or possible
      and usually suffices.

PMID- 8131549
TI  - Biphasic extrathoracic pressure CPR. A human pilot study.
AB  - HYPOTHESIS: Alternating intrathoracic pressure by means of a chest cuirass can
      cause perfusion and ventilation equal to or better than standard cardiopulmonary
      resuscitation (CPR) for humans in cardiac arrest. DESIGN: Nonrandomized,
      nonblinded, crossover pilot study. SETTING: Large urban emergency department.
      SUBJECTS: Five adult normothermic, nontraumatic, out-of-hospital cardiac arrest
      patients unresponsive to standard advanced cardiac life support. METHOD: Right
      atrial and aortic catheters were inserted for pressure measurement and blood gas
      analysis while the patient was receiving standard CPR by a pneumatic compression
      device (Thumper). The Thumper was then replaced by a chest cuirass (Hayek
      Oscillator). Pressure and blood gas measurements were then repeated. RESULTS: The
      coronary perfusion pressure increased from -1.2 +/- 8.6 mm Hg to 6.2 +/- 6.9 mm
      Hg for a mean change of 7.4 +/- 3.1 mm Hg (p = 0.006). The compression phase
      gradient increased 10.0 +/- 21.9 mm Hg (p = 0.364). The venous to arterial PCO2
      gradient decreased 44.5 +/- 32.3 mm Hg (p = 0.070). The oxygen extraction ratio
      increased 1.6 +/- 9.4 percent (p = 0.761). The mean arterial PO2 and PCO2 changed
      from 252 to 240 mm Hg (p = 0.836) and from 53 to 66 (p = 0.172) mm Hg,
      respectively. CONCLUSION: The Hayek Oscillator chest cuirass produced a
      significant improvement in the coronary perfusion pressure. There was a trend for
      improved systemic perfusion as indicated by an improved compression phase
      gradient and venous to arterial PCO2 gradient, although this was not supported by
      the lack of improvement in the oxygen extraction ratio. The cuirass also
      adequately oxygenates and ventilates unassisted by positive pressure ventilation.

PMID- 8131550
TI  - Fatal pulmonary embolism in spinal cord injury.
AB  - Fatal pulmonary embolism (PE) is a major cause of mortality in patients with
      spinal cord injury. In order to ascertain those characteristics that might
      predict this event, we reviewed the records of all patients with autopsy-proven
      massive PE admitted to a regional spinal cord care center over a 5-year period.
      The information analyzed included patient age, sex, race, height, weight, type of
      accident, prior use of tobacco, alcohol, or narcotic drugs, level of injury,
      presence of spasticity, surgical procedures, infections, transfusions, and type
      of anticoagulant prophylaxis. Forty-two concurrently hospitalized patients with
      spinal cord injury served as control subjects. Significant differences between
      cases and control subjects were observed for level of injury (fewer thoracic and
      lumbar injuries in cases, p = 0.04), less spasticity in cases (p = 0.01), and
      greater body mass index in cases (p = 0.01). There was also a trend toward more
      advanced age in the cases (p = 0.1) and more frequent serious infections (p =
      0.08). Lastly, low molecular weight heparin had been used as thromboprophylaxis
      in a greater proportion of control subjects than cases (60 percent vs 22 percent,
      p = 0.07), suggesting that low molecular weight heparin may be more effective in
      preventing fatal PE than unfractionated heparin.

PMID- 8131551
TI  - Autologous blood transfusion for pulmonary and mediastinal surgery in 144
      patients. The effectiveness of recombinant erythropoietin injection.
AB  - Preserved autologous transfusions have been performed for elective pulmonary and
      mediastinal surgery to prevent the adverse effects of homologous transfusions.
      Autologous blood was collected preoperatively from 144 patients. The collected
      blood volume ranged from 400 to 1,600 ml with a mean volume of 544 ml. In four
      patients with benign diseases, 1,200 to 1,600 ml of blood was collected using
      3,000 U of intravenous recombinant human erythropoietin (rh-EPO) administered
      every other day. One hundred twenty-three of these patients (85 percent) did not
      require a homologous transfusion. In the 84 patients undergoing either a
      pneumonectomy, lobectomy, or segmentectomy, 68 (81 percent) avoided homologous
      blood exposure. A patient with rh-EPO who bled 2,000 g during surgery received an
      autotransfusion of only 1,400 ml and his postoperative course was uneventful.
      Preserved autologous blood collected after rh-EPO injections is an effective
      method for minimizing homologous blood transfusions in pulmonary and mediastinal
      surgery.

PMID- 8131552
TI  - Changes in work of breathing during continuous positive airway pressure with
      increased airway resistance.
AB  - STUDY OBJECTIVES: To describe the importance of measuring work of breathing (WOB)
      in patients with high airway resistance (Raw) during continuous positive airway
      pressure (CPAP) support. DESIGN: Fundamental study using an advanced model lung
      and a pulmonary function monitor. SETTING: A research laboratory at the ICU of a
      university hospital. INTERVENTIONS: Spontaneous breathing (tidal volume x
      respiratory rate: 400 ml x 15 min-1) was simulated with a time-cycled jet-flow
      generator. The CPAP and Raw were adjusted to 0, 5, and 10 cm H2O and to 5, 10,
      and 20 cm H2O.L-1.s-1, respectively. MEASUREMENTS AND RESULTS: Using four
      advanced demand-flow system type ventilators (Evita, 7200a, Servo 900C, and Servo
      300), a two-bellows-in-a-box type model lung, and a pulmonary function monitor
      with an esophageal catheter (CP-100), we measured WOB during CPAP with increased
      Raw. The WOB of the model lung increased significantly with increase in CPAP. The
      WOB of the model lung also increased significantly with increase in Raw for all
      ventilators tested in this study; some values showed over 1 J.L-1. The WOB under
      the Servo 300 exhibited the lowest values in all situations of all the
      ventilators tested in this study. CONCLUSIONS: Patients with high Raw may suffer
      excessive WOB even during CPAP with advanced demand-flow system type ventilators.
      It is vital to monitor WOB continuously using an adequate pulmonary function
      monitor such as that used in this study.

PMID- 8131553
TI  - Use of metallic stents in relapsing polychondritis.
AB  - Relapsing polychondritis is a rare multisystem disease. We describe the
      presentation and treatment of a patient with relapsing polychondritis and review
      the literature. This patient had involvement of the tracheobronchial tree
      requiring insertion of metallic stents.

PMID- 8131554
TI  - Intrapleural urokinase in the treatment of loculated pleural effusions.
AB  - The purpose of this study was to assess the value of intrapleural urokinase (UK)
      instillations in enhancing tube drainage of loculated, complex pleural effusions.
      Tube thoracostomy has variable success in the treatment of complex pleural
      effusions, with limitations because of viscous fluid, improper tube position or
      kinking, and, most importantly, loculation. In the past, intrapleural
      administration of streptokinase has been used to lyse locules. In this study,
      eight patients with nine loculated pleural processes were treated with
      intrapleural instillations of UK. Six patients had previously undergone
      unsuccessful conventional tube drainage. Loculation was suggested by persistent
      fluid despite an adequate trial of simple drainage, radiographic demonstration of
      septation, or drainage of a volume of fluid far less than expected by a computed
      tomography scan. After instillation of a UK solution, the tubes were clamped for
      30 to 180 min and then placed back to suction. Five pleural cavities with disease
      6 to 18 days old showed complete resolution, and clinical improvement occurred.
      Three pleural processes showed improvement and one showed no improvement, with
      disease ranging from 23 days to 3 months. No complications were seen. These
      results suggest that UK instillations may enhance tube drainage of loculated
      pleural fluid in the early phase, before fibrosis has developed.

PMID- 8131555
TI  - Femoral vein pulmonary artery catheterization in the intensive care unit.
AB  - OBJECTIVES: To evaluate the success and complications of pulmonary artery
      catheterization via the femoral vein without the use of fluoroscopy, in the
      medical ICU. DESIGN: We retrospectively reviewed the charts of all patients
      receiving pulmonary artery catheters through the femoral vein in the medical ICU
      between July 1, 1988 and June 30, 1992. SETTING: Medical ICU at Bronx Municipal
      Hospital Center. PATIENTS: Thirty-three patients were studied (20 male and 13
      female). The patients ranged in age from 24 to 83 years, with the mean age of 56
      years. The condition at the time of catheterization was classified as septic
      shock (n = 22), gastrointestinal bleed (n = 7), cardiogenic shock (n = 1),
      cardiac tamponade (n = 1), preoperative (n = 1), or drug overdose (n = 1).
      MEASUREMENTS: In each case, pulmonary artery pressure tracings,
      electrocardiographic recordings, procedure, and nursing notes were reviewed from
      the time of catheter insertion. Charts were also analyzed for evidence of
      catheter-related septicemia, deep vein thrombosis, pulmonary embolism, or
      problems developing at the insertion site. RESULTS: Femoral vein pulmonary artery
      catheterization was performed successfully in 37 of 39 attempts (95 percent
      success rate) without the use of fluoroscopy. Five of the 33 patients studied had
      more than one femoral vein pulmonary artery catheter during their hospital
      course. Four of them had two femoral vein pulmonary artery catheters and the
      fifth patient had three femoral vein pulmonary artery catheters. Overall, 39
      attempts at femoral vein pulmonary artery catheterization were made in the 33
      patients studied. Three patients had 10- to 19-beat ventricular tachycardia (7.7
      percent incidence) precluding catheter insertion via this approach in two
      instances. There was no clinical evidence of major hematomas or hemorrhages,
      catheter-related septicemia, deep vein thrombosis, or pulmonary emboli in any of
      our patients. CONCLUSION: Femoral vein pulmonary artery catheterization without
      the use of fluoroscopy is safe and effective.

PMID- 8131556
TI  - The stomach is not a source for colonization of the upper respiratory tract and
      pneumonia in ICU patients.
AB  - STUDY OBJECTIVE: To study sequences of colonization of different species of
      microorganisms and to determine the importance of gastric colonization for the
      development of nosocomial pneumonia. DESIGN: A prospective study. SETTING: Two
      identical ICUs of a university hospital. PATIENTS: Sixty-four patients admitted
      to ICU for at least 5 days; 59 were intubated. INTERVENTIONS: Microbiologic
      cultures of serially taken samples of gastric aspirates, oropharyngeal swabs, and
      tracheal aspirates were performed at the time of ICU admission and subsequently
      twice a week. Diagnosis of pneumonia was based on quantitative cultures from
      bronchoalveolar lavage (BAL) and protected specimen brush (PSB). Sequences of
      colonization were examined by comparing isolates of the same species, with
      concordance of minimum inhibitory concentration values to six antibiotics.
      MEASUREMENTS AND RESULTS: Eleven patients developed 14 episodes of nosocomial
      pneumonia, yielding 20 species of microorganisms. Seventeen of 20 species (85
      percent), associated with pneumonia, were cultured, previous to or on the day of
      diagnosis, from tracheal aspirates, and 6 of 20 (30 percent) species were
      cultured from gastric samples. A sequence of colonization from the stomach to the
      upper respiratory tract eventually leading to pneumonia was not observed in any
      of the six species. Initial colonization with Pseudomonas aeruginosa and
      Enterobacter species was more often demonstrated in the trachea (16/24 and 13/25
      cases) as compared with the stomach (1/24 and 6/25 cases; p < 0.0001 and p = 0.02
      respectively). In contrast, initial colonization with Klebsiella species and
      Enterococcus faecalis was more frequently demonstrated in the stomach (13/28 and
      8/15 cases) as compared with the trachea (6/28 and 0/15 cases; p = 0.02 and p <
      0.0001, respectively). CONCLUSIONS: Based on studying sequences of colonization
      in ICU patients, we concluded that the stomach is unlikely to be an important
      source of pathogens leading to nosocomial pneumonia as diagnosed by BAL/PSB.
      Furthermore, the initial site and route of colonization might not be the same for
      all microorganisms.

PMID- 8131557
TI  - Accuracy of portable chest radiography in the critical care setting. Diagnosis of
      pneumonia based on quantitative cultures obtained from protected brush catheter.
AB  - Sixty-six supine portable chest radiographs done on the day of bronchoscopy in 62
      critical care unit patients suspected of having pneumonia were examined in a
      blinded fashion by two radiologists. Quantitative culture results obtained from
      protected brush catheter (PBC) specimens were compared with chest radiograph
      scores. For one observer, the sensitivity of the chest radiograph for predicting
      the presence of positive culture results was 0.60, specificity was 0.29, overall
      agreement was 0.41, positive predictive value was 0.34, and negative predictive
      value was 0.55. For the second observer, the values were as follows: sensitivity,
      0.64; specificity, 0.27; overall agreement, 0.41; positive predictive value,
      0.35; and negative predictive value, 0.55. The kappa statistic was calculated at
      0.27 indicating marginal interobserver reproducibility. We conclude the portable
      chest radiograph in the critical care setting is not accurate in predicting the
      presence of pneumonia when the diagnosis is based on quantitative cultures
      obtained from protected brush catheter specimens.

PMID- 8131558
TI  - Rapid visualization of massive pulmonary emboli utilizing intravascular
      ultrasound.
AB  - Massive pulmonary embolism may result in rapid deterioration prior to diagnostic
      and therapeutic intervention. Intravascular ultrasound imaging has been utilized
      previously to evaluate vascular abnormalities as well as normal human pulmonary
      arteries. We employed this technique to rapidly identify massive pulmonary emboli
      located in the main pulmonary arteries of two patients. The presence of these
      emboli was confirmed with pulmonary arteriography. Intravascular ultrasound may
      be utilized to rapidly confirm the presence of large proximal pulmonary emboli.

PMID- 8131559
TI  - Asthma requiring mechanical ventilation. A low morbidity approach.
AB  - STUDY OBJECTIVE: There is considerable uncertainty about the clinical features,
      respiratory physiology, and optimal management of patients with asthma requiring
      mechanical ventilation. Furthermore, the ventilatory and pharmacologic management
      of asthma requiring mechanical ventilation remain controversial. We hypothesized
      (1) that there are clinically identifiable and pathophysiologically different
      subgroups presenting with asthma requiring ventilation; (2) that lower dose
      steroid therapy (< 400 mg/d intravenous hydrocortisone) is adequate; (3) that
      permissive hypercapnia is safe; (4) that prolonged paralysis is generally
      unnecessary; and (5) that clinical outcome would be favorable in patients treated
      with this approach. DESIGN: Review of medical records and intensive care charts
      and statistical analysis of findings. SETTING: ICU of tertiary institution.
      PATIENTS: Thirty-five consecutive cases of life-threatening asthma requiring
      mechanic ventilation. RESULTS: Three clinical subgroups of ventilation-requiring
      asthmatics could be identified. Those presenting with steady deterioration (10),
      those with unstable asthma followed by a sudden "dip" (16), and those with a
      sudden unexpected dip (9). Patients in the first group had a significantly lower
      PaCO2 (p < 0.01) at presentation, but required ventilation for longer periods.
      Those in the second group had a significantly higher PaCO2 (p < 0.01) and
      required ventilation for a shorter period. Those in the third group had an
      intermediate PaCO2 level before intubation and the shortest period (p < 0.01) of
      mechanical ventilation. Five patients experienced their sudden dip after
      ingesting aspirin. Ten cases received "high" dose hydrocortisone therapy (mean:
      980 mg/24 h), and 25 received lower dose hydrocortisone (mean: 341 mg/24 h). No
      differences in illness severity at presentation or outcome could be detected
      between these two groups. Mean duration of ventilatory support was 36 h and mean
      duration of the ICU stay 52.1 h. Muscle relaxation was used in 12 patients for a
      mean period of 11.1 h. One patient was brain dead on arrival. All others
      survived. CONCLUSIONS: Life threatening asthma is an endpoint for several
      different clinical patterns of disease. No major clinical advantage could be
      found in our group of patients when high-dose steroids were used. Long-term use
      of muscle relaxants and prolonged mechanic ventilation are rarely needed in the
      management of patients with life-threatening asthma and excellent results can be
      achieved with a relatively simple management strategy.

PMID- 8131560
TI  - Basic mechanisms in congestive heart failure. Recognizing the role of
      proinflammatory cytokines.

PMID- 8131561
TI  - An unusual complication of central venous catheterization.

PMID- 8131563
TI  - Measuring the quality of life before and after bilateral lung transplantation in
      patients with cystic fibrosis.
AB  - Lung transplantation is an important topic today in healthcare policy because the
      technique is new and costly. One of the important issues in the evaluation of
      lung transplantation is quality of life. The quality of life after lung
      transplantation must be relatively high compared with other forms of medical care
      to legitimize the high costs of transplantation. Quantifying the quality of life
      after lung transplantation and other medical therapies is possible with general
      measurements of quality of life. In a pilot study of six patients with cystic
      fibrosis, the quality of life, both before and after lung transplantation, was
      measured by the following five instruments: (1) standard gamble, (2) time trade
      off, (3) the Karnofsky performance status, (4) the EuroQol visual analog scale,
      and (5) the Nottingham health profile. This pilot study demonstrates that the
      introduced methodology is feasible. The preliminary results suggest that the
      improvement in quality of life for patients with cystic fibrosis after bilateral
      lung transplantation is comparable to the improvement in quality of life after
      heart transplantation.

PMID- 8131562
TI  - Pleurodesis with polidocanol in pigs. An experimental study.
AB  - Polidocanol was instilled in five pleural cavities of three pigs. Adhesions
      formed in all. Adhesion distribution varied from covering a minor part to most of
      the lung, depending on the amount of polidocanol. One control cavity treated with
      sodium chloride was unaffected. Microscopy showed fibrous bridges between the
      pleural layers and mild submesothelial fibrosis and inflammation.

PMID- 8131564
TI  - Fever, cough, pleuritic chest pain, and pleural fluid eosinophilia in a 30-year
      old man.

PMID- 8131565
TI  - Magnetic resonance imaging marketing and investment. Tensions between the forces
      of business and the practice of medicine.

PMID- 8131566
TI  - Pneumatosis intestinalis and active cytomegaloviral infection after lung
      transplantation. Groningen Lung Transplant Group.
AB  - Pneumatosis intestinalis occurred in a patient with a primary cytomegaloviral
      (CMV) infection with pneumonitis 6 weeks after single lung transplantation for
      primary pulmonary hypertension. The possible causal relationship between
      pneumatosis intestinalis, an uncommon disorder with an obscure pathogenesis, and
      active CMV infection has been observed before; however, to our knowledge, this is
      the first report of this combination after lung transplantation. The patient had
      no abdominal complaints, and after treatment of the CMV infection, the
      pneumatosis intestinalis resolved spontaneously. The early diagnosis of active
      CMV infection and the prevention of unnecessary abdominal surgery were essential
      in this case.

PMID- 8131567
TI  - Right-to-left interatrial shunt causing platypnea after pneumonectomy. A recent
      experience and diagnostic value of dynamic magnetic resonance imaging.
AB  - Shortness of breath after pneumonectomy is a common finding that has multiple
      causes. We report the cases of two patients with shortness of breath on assuming
      an upright posture (platypnea) that followed pneumonectomy; these individuals
      developed right-to-left shunt across a patent foramen ovale (PFO) with normal
      right-sided intracardiac pressures. Both contrast echocardiography and magnetic
      resonance imaging (MRI), including a recently introduced dynamic ultrafast
      imaging technique, proved helpful in diagnosing this condition noninvasively.

PMID- 8131568
TI  - Concertina-like phenomenon in ventricular preexcitation due to spontaneous
      atrioventricular nodal Wenckebach periodicity.
AB  - Electrophysiologic study and radiofrequency ablation therapy were performed in a
      28-year-old male patient with the Wolff-Parkinson-White syndrome and
      electrocardiographic manifestation of concertina phenomenon. His bundle
      recordings showed a sinus cycle length of 720 = ms with a cyclic variation of QRS
      morphologies of every 3 beats and an antidromic atrial echo following the last
      fully preexcited QRS complex. After successful radiofrequency ablation of a left
      posterior accessory pathway, spontaneous 3:2 atrioventricular nodal Wenckebach
      periodicity was noted and the mechanism of the concertina phenomenon was
      unraveled.

PMID- 8131569
TI  - Pneumonitis associated with natural and recombinant interferon alfa therapy for
      chronic hepatitis C.
AB  - We report three cases of chronic hepatitis C (HC) with pneumonitis, suspected to
      be caused by natural and recombinant interferon (INF) alfa treatments. The
      patients were administered INF through intramuscular injection. All three
      patients developed acute respiratory failure (PaO2 < or = 60 mm Hg) with
      bilateral lung infiltration. One of the patient's condition improved after the
      cessation of INF treatment, without any other therapy. The other two patients
      were administered corticosteroids, and one patient's condition improved, while in
      the other patient the pneumonitis persisted, even after a high dose of
      corticosteroids. To our knowledge, these three cases are the first report of
      pneumonitis associated with INF alfa in patients with chronic HC.

PMID- 8131570
TI  - Malignant thymoma. A complicated triad of SVC syndrome, cardiac tamponade, and
      DIC.
AB  - A patient presented with multisystem disease due to a very aggressive malignant
      thymoma. The case was complicated by the triad of cardiac tamponade, superior
      vena cava (SVC) syndrome, and disseminated intravascular coagulation (DIC). A
      review of the English literature reveals this to be a unique constellation of
      clinical symptoms and that DIC was heretofore unreported.

PMID- 8131571
TI  - Factitious hemoptysis. Adding to the differential diagnosis.
AB  - BACKGROUND: We report a dramatic case of factitious hemoptysis in a 36-year-old
      black man who presented with hemoptysis and chest pain. METHODS: After an
      exhaustive evaluation, including many invasive procedures, we discovered that the
      patient's complaints were fabricated, although the method used to simulate
      hemoptysis was not determined. Documentation was obtained of at least 23 other
      hospital admissions with similar complaints. During these hospitalizations,
      numerous diagnostic procedures were performed, including 16 fiberoptic
      bronchoscopies and 3 cardiac catheterizations, with negative results. RESULTS:
      Review of 11 other reported cases of factitious hemoptysis reveals that these
      patients are generally young (mean age, 32 years; range, 21 to 47 years) and
      often health-care workers (4 of 12 cases) and that the method of simulating
      hemoptysis, if discovered, usually involves a self-inflicted wound (5 cases).
      CONCLUSION: A factitious cause should be considered in the differential diagnosis
      of hemoptysis of unclear etiology, especially when the medical history or the
      patient's behavior is unusual.

PMID- 8131572
TI  - Transesophageal echocardiography of right atrial metastasis of a hepatocellular
      carcinoma.
AB  - Antemortem diagnosis of cardiac metastases of a hepatocellular carcinoma is
      rarely observed. In a 52-year-old female patient with a history of posthepatitic
      cirrhosis and partial hepatectomy, transthoracic echocardiography brought to
      light a mass in the right atrium. After location and characterization of the
      tumor by transesophageal echocardiography, a transvenous biopsy confirmed the
      diagnosis of metastasis of a hepatocellular carcinoma.

PMID- 8131573
TI  - Obstructive sleep apnea syndrome in acid maltase deficiency.
AB  - A patient with adult acid maltase deficiency (AMD) developed severe obstructive
      sleep apnea (OSA) and respiratory insufficiency. Weaning failure was followed by
      diffuse pneumonia and death. At autopsy, profound muscle replacement by
      fibrofatty tissue was noted in the tongue and diaphragm, while the accessory and
      nonrespiratory muscles were variably preserved. To our knowledge, this case
      represents the first detailed clinical description of OSA associated with adult
      AMD. In addition, we suggest that severe tongue weakness due to fatty
      metamorphosis, in concert with macroglossia, provides a unique pathophysiologic
      mechanism for OSA.

PMID- 8131574
TI  - Recurrent acoustic neuroma presenting as central alveolar hypoventilation.
AB  - Centrally mediated hypoventilation causes respiratory failure without respiratory
      distress. We present a case of recurrent acoustic neuroma at the cerebellopontine
      angle causing acute and chronic respiratory failure. Tumor resection eliminated
      recurrence of respiratory failure.

PMID- 8131575
TI  - Panhypopituitarism caused by solitary parasellar metastasis from lung cancer.
AB  - Clinical panhypopituitarism caused by cancer with parasellar metastasis and
      hypothalamic invasion is very rare. This report concerns a lung cancer patient
      who had solitary parasellar metastasis with diabetes insipidus and
      panhypopituitarism as an initial manifestation, which was documented by contrast
      enhanced computed tomographic scan, Gd-DTPA-enhanced magnetic resonance imaging,
      and endocrinologic studies.

PMID- 8131576
TI  - Endobronchial urokinase for dissolution of massive clot following transbronchial
      biopsy.
AB  - Endobronchial streptokinase has been used previously to dissolve blood clots
      caused by massive spontaneous hemoptysis, in settings including sarcoidosis,
      cavitary histoplasmosis, and multiple myeloma. To our knowledge, however, the use
      of thrombolytic agents to dissolve clots following transbronchial biopsy has not
      been reported previously. We describe a patient in whom endobronchial urokinase
      was used for successful dissolution of clots secondary to massive bleeding after
      transbronchial biopsy.

PMID- 8131577
TI  - Use of plasma for arterial blood gas analysis in leukemia.
AB  - A 63-year-old patient with chronic lymphocytic leukemia presented with severe
      hypoxemia. However, the patient's hemoglobin saturation, measured by an ear
      oximeter, was normal. Although his WBC count was approximately
      1,000,000/microliters, hypoxemia could not be explained by the consumption of
      oxygen by leukocytes. Therefore, arterial blood gas values were analyzed in both
      plasma as well as in whole blood. The PaO2 in the plasma was much higher than in
      whole blood and corresponded with the hemoglobin saturation measured by the ear
      oximeter. These findings suggest that very high leukocyte counts may interfere
      with the measurement of oxygen tension and that plasma may be used for blood gas
      analysis in this situation.

PMID- 8131578
TI  - Idiopathic lipoid pneumonia in an adult treated with prednisolone.
AB  - The treatment of lipoid pneumonia, an uncommon chronic lung condition, is
      generally conservative. We describe a patient with idiopathic lipoid pneumonia
      who was successfully treated with oral steroids with improvement of chest
      radiographic abnormalities.

PMID- 8131579
TI  - Treatment of bronchopleural fistula after pneumonectomy by using an omental
      pedicle.
AB  - Dehiscence of the bronchial stump, particularly following pneumonectomy, is one
      of the most serious complications in lung surgery. Various approaches to this
      problem have been tried. Two patients with postpneumonectomy bronchopleural
      fistula were treated successfully by using a pedicle of the greater omentum.

PMID- 8131580
TI  - Coronary artery fistula diagnosed by transesophageal echocardiography.
AB  - Coronary artery fistulas have been traditionally diagnosed by angiography. This
      report describes a congenital and a traumatic coronary artery fistula diagnosed
      by transesophageal echocardiography. Transesophageal echocardiography was
      superior to transthoracic echocardiography in both cases and to angiography in
      one case. Transesophageal echocardiography may now be the procedure of choice in
      diagnosing coronary fistula.

PMID- 8131581
TI  - Prolonged use of an endotracheal tube changer in a pediatric patient with a
      potentially compromised airway.
AB  - A 14-year-old obese male patient presented following a motor vehicle accident
      with multiple injuries and respiratory failure requiring endotracheal intubation
      and mechanical ventilation. Because of potential problems with a difficult
      airway, an endotracheal tube changer was used at the time of extubation and left
      in place for a prolonged period of time. Leaving the tube changer in place
      maintained access to the airway. Additionally, the manipulation of the tube
      changer was used to stimulate the cough reflex.

PMID- 8131582
TI  - An interleukin-6 secreting myxoma in a hypertrophic left ventricle.
AB  - We describe a patient who had both a left ventricular myxoma and left ventricular
      hypertrophy; the myxoma was subsequently excised and revealed to produce
      interleukin-6. The combination of left ventricular myxoma and ventricular
      hypertrophy is uncommon. Interleukin-6 secreted from the myxoma may be an
      important factor in the pathogenesis of ventricular hypertrophy in this patient.

PMID- 8131583
TI  - Boerhaave's syndrome complicated by a large bronchopleural fistula.
AB  - We report a case Boerhaave's syndrome complicated by a large bronchopleural
      fistula due to autolysis of lung parenchyma by gastric contents, a complication
      not previously documented to our knowledge.

PMID- 8131584
TI  - Orthodeoxia in amiodarone-induced acute reversible pulmonary damage.
AB  - A case of acute reversible pulmonary damage from amiodarone is described.
      Pulmonary infiltrates had a basal predominance. The histopathologic picture was
      that of acute alveolitis. Orthodeoxia was evident on blood gas analysis; the PaO2
      was 73 mm Hg on recumbency, and the PaO2 was 57 mm Hg in the upright position.
      Partial arterial resaturation was evident on exercise (PaO2, 64 mm Hg).

PMID- 8131585
TI  - Increased level of circulating gamma/delta T cells in a patient with eosinophilic
      granuloma.
AB  - A patient with eosinophilic granuloma, histologically confirmed from open lung
      biopsy specimen, had a history of scarlet fever and a prominently high level of
      circulating gamma/delta T cells (25 percent) in comparison with normal levels (<
      10 percent). Despite steroid therapy, the levels were persistently high. To our
      knowledge, this is the first report of an increased level of circulating
      gamma/delta T cells in a patient with eosinophilic granuloma.

PMID- 8131586
TI  - Exogenous lipoid pneumonia due to nasal application of petroleum jelly.
AB  - We describe a patient who presented with a history of unexplained exertional
      dyspnea and pulmonary infiltrates. She was evaluated for interstitial lung
      disease, presumed to be idiopathic and underwent an open lung biopsy. The
      pathologic findings were compatible with exogenous lipoid pneumonia and her
      history revealed longstanding use of intranasal petroleum jelly (Vaseline) at
      bedtime.

PMID- 8131587
TI  - Evaluation of definitions of sepsis.

PMID- 8131588
TI  - Antithrombotic therapy in paroxysmal atrial fibrillation.

PMID- 8131589
TI  - Percutaneous lung biopsy in the diagnosis of bronchiolitis obliterans organizing
      pneumonia.

PMID- 8131590
TI  - Perivascular fibrosis of muscular pulmonary arteries in COPD.

PMID- 8131591
TI  - Serum-effusion albumin gradient in separation of transudative and exudative
      pleural effusions.

PMID- 8131592
TI  - Oximeter malfunction.

PMID- 8131593
TI  - Cyclophosphamide induces false-positive results in detection of aspergillus
      antigen in urine.

PMID- 8131594
TI  - Iatrogenic aspiration. Follow-up.

PMID- 8131595
TI  - Quantitative study of the bronchial bacterial flora in acute exacerbations of
      chronic bronchitis.

PMID- 8131596
TI  - Adhesion to fibronectin augments tumor necrosis factor production by human
      alveolar macrophages.

PMID- 8131597
TI  - Attenuation of complement-mediated acute lung injury in rabbits and transgenic
      mice by C-reactive protein.

PMID- 8131598
TI  - Are pulmonary capillaries susceptible to mechanical stress?

PMID- 8131599
TI  - Centripetal tension and endothelial retraction.

PMID- 8131600
TI  - Pressure-targeted, lung-protective ventilatory support in acute lung injury.

PMID- 8131601
TI  - Inflation pressure and lung vascular injury in preterm lambs.

PMID- 8131602
TI  - Alveolar type II cell Na,K-ATPase is upregulated during mechanical ventilation
      induced pulmonary edema.

PMID- 8131603
TI  - Repair after acute lung injury.

PMID- 8131604
TI  - Intra-alveolar fibrosis. Alpha v beta 3 integrin and chondroitin sulfate
      proteoglycan mediate endothelial cell adhesion, migration, and invasion into the
      fibrin provisional matrix.

PMID- 8131605
TI  - Acute lung injury. A transgenic murine model of intra-alveolar fibrosis.

PMID- 8131606
TI  - What happens to survivors of the adult respiratory distress syndrome?

PMID- 8131607
TI  - Elevated lavage levels of N-terminal peptide of type III procollagen are
      associated with increased fatality in adult respiratory distress syndrome.

PMID- 8131608
TI  - Fibroproliferation in late adult respiratory distress syndrome. Pathophysiology,
      clinical and laboratory manifestations, and response to corticosteroid rescue
      treatment.

PMID- 8131609
TI  - The acute respiratory distress syndrome. Historic perspective.

PMID- 8131610
TI  - Endotoxemia enhances pulmonary mononuclear cell uptake of circulating particles
      and pathogens in a species without pulmonary intravascular macrophages.

PMID- 8131611
TI  - Endotoxin upregulates expression of an antimicrobial peptide gene in mammalian
      airway epithelial cells.

PMID- 8131612
TI  - Role of tyrosine kinases and MAP kinase in neutrophils stimulated by
      lipopolysaccharide.

PMID- 8131613
TI  - Clinical sepsis trials.

PMID- 8131614
TI  - Protein-phospholipid interactions in pulmonary surfactant. The Parker B. Francis
      Lectureship.
AB  - SP-B is the protein in pulmonary surfactant with the greatest capacity to augment
      the phospholipids, ability to resist surface tension, and capability to prevent
      collapse of pulmonary alveoli. Synthetic peptides derived from the structure of
      SP-B and simplified analogues of these SP-B-derived peptides were found by
      tryptophan fluorescence to partition within the phospholipid layer in contact
      with both polar head groups and acyl side chains of the phospholipids. The
      intermittent hydrophilic basic residues were found to be essential for full
      activity, probably because of electrostatic interactions formed with phosphates
      of the polar head groups. The hydrophobic stretches of residues in SP-B and the
      related peptides supplement the activity through interaction with the
      phospholipid acyl side chains. By increasing intermolecular and intramolecular
      order of the phospholipid layer and thereby stability of the layer, the SP-B
      analogues provide strong surfactant activity. Simplified peptide analogues of SP
      B, dispersed in DPPC and POPG, provide strong surfactant activity in vitro and in
      the lungs of premature infant rabbits, rhesus monkeys, and humans.

PMID- 8131615
TI  - Amplitude-modulated ventilation. Effects in acute lung injury and
      characterization of mechanisms of action.

PMID- 8131616
TI  - Function of the alveolar epithelial barrier under pathologic conditions.

PMID- 8131617
TI  - Peroxynitrite inhibition of oxygen consumption and ion transport in alveolar type
      II pneumocytes.

PMID- 8131618
TI  - Hyperoxia increases active alveolar Na+ resorption in vivo and type II cell Na,K
      ATPase in vitro.

PMID- 8131619
TI  - In vivo and in vitro expression of metallothionein in injured type II alveolar
      epithelial cells.

PMID- 8131620
TI  - Free radical chemistry of nitric oxide. Looking at the dark side.

PMID- 8131621
TI  - Structural and functional alterations of surfactant protein A by peroxynitrite.

PMID- 8131622
TI  - NADPH oxidase-derived reactive oxygen intermediates regulate tyrosine
      phosphorylation in human neutrophils.

PMID- 8131623
TI  - Effects of cytokines and endotoxin on lung manganese superoxide dismutase
      expression and immunohistochemical distribution.

PMID- 8131624
TI  - Interleukin-1-induced tolerance to IL-1-induced oxidative lung injury in rats.

PMID- 8131625
TI  - Inhaling nitric oxide: a selective pulmonary vasodilator and bronchodilator.

PMID- 8131626
TI  - Nitric oxide inhalation. Effects on the ovine neonatal pulmonary and systemic
      circulations.

PMID- 8131627
TI  - Efficacy of inhalational nitric oxide therapy in the clinical management of
      persistent pulmonary hypertension of the newborn.

PMID- 8131628
TI  - Interleukin-8 and related chemotactic cytokines. The Giles Filley Lecture.

PMID- 8131629
TI  - Chemotactic cytokines in the established adult respiratory distress syndrome and
      at-risk patients.

PMID- 8131630
TI  - Lipopolysaccharide-stimulated human alveolar macrophages produce mRNA for a
      spectrum of a-chemokines.

PMID- 8131631
TI  - Priming of phospholipases A2 of human neutrophils by tumor necrosis factor.

PMID- 8131632
TI  - In vitro activity of rufloxacin against Listeria monocytogenes, Legionella
      pneumophila, and Chlamydia trachomatis.
AB  - The in vitro activity of a new fluoroquinolone, rufloxacin, was determined
      against both clinical isolates and standard strains of Legionella pneumophila,
      Chlamydia trachomatis, and Listeria monocytogenes and compared to that of
      ciprofloxacin, ofloxacin, and erythromycin. Among the antibacterials tested
      erythromycin was the most active. Rufloxacin inhibited the growth of L.
      pneumophila at concentrations in the range of 0.06-0.25 mg/l, that of C.
      trachomatis at concentrations in the range of 2-4, and that of L. monocytogenes
      at concentrations in the range of 1-2 mg/l. Rufloxacin demonstrated approximately
      the same activity as ciprofloxacin against C. trachomatis, but twice as less
      potency as ofloxacin and erythromycin against L. pneumophila, L. monocytogenes,
      and C. trachomatis, and twice as less potency as ciprofloxacin against L.
      pneumophila.

PMID- 8131633
TI  - Antibiotics alter interactions of Staphylococcus aureus with collagenous
      substrata.
AB  - The effects of sub-minimum inhibitory concentrations (sub-MICs) of three
      antibiotics affecting the biosynthesis of peptidoglycan on the interactions of
      Staphylococcus aureus strains with collagenous substrata were evaluated. In a
      system measuring binding of 125I-labeled collagen, growth of bacteria in the
      presence of one-quarter MIC of cloxacillin and vancomycin reduced the number of
      collagen binding sites on the surface of bacteria. Growth in the presence of
      cefpodoxime reduced the number of collagen binding sites in one strain and
      increased it in another. Cefpodoxime also increased the dissociation constant of
      collagen binding to bacteria, 2- to 3-fold, while the other two antibiotics did
      not affect the affinity of the interaction. In a system measuring adhesion of
      125I-labeled bacteria to collagen-coated surfaces or cartilage, bacteria grown in
      the presence of cloxacillin and vancomycin attached to varying degrees depending
      on the strain. In contrast, compared to untreated controls as well as to bacteria
      treated with the other two antibiotics, growth in the presence of cefpodoxime
      significantly reduced adhesion of the majority of strains tested. Sub-MICs of
      antibiotics appear to affect staphylococcal adhesion to collagenous substrata
      with cefpodoxime exhibiting the strongest effect. The critical factor in reducing
      bacterial adhesion seems not to be the number of bacterial binding sites for
      collagen, but the affinity of the interaction.

PMID- 8131634
TI  - Influence of membrane composition of various parasites on the inhibitory activity
      of a series of bipyridyl analogues.
AB  - In a previous report the dependence of the antimycoplasmal activity of bipyridyl
      analogues on the presence of Cu+ ions has been shown. The inhibitory activity of
      these compounds has now been studied against Escherichia coli mycobacteria and
      Candida albicans in the absence and presence of Cu2+ ions using growth kinetic
      techniques. It was found that the inhibitory activity against E. coli increases
      in the presence of Cu2+ ions. In contrast, no additional effect of Cu2+ ions is
      observed for the inhibitory activity against mycobacteria. Some of the
      derivatives show very promising activity even against Mycobacterium avium
      strains. More complicated is the effect of Cu2+ ions on the inhibitory activity
      of the derivatives against C. albicans. For isoquinolones the observed delay in
      onset of inhibitors is reduced and no influence on the inhibitory activity is
      observed. The addition of Cu2+ ions to the phenanthrolines leads in contrast to a
      decrease in antifungal activity. The possible influence of membrane properties of
      the studied microorganism on the effect of Cu2+ ions is discussed.

PMID- 8131635
TI  - Effect of fluconazole prophylaxis on fever and use of amphotericin in neutropenic
      cancer patients. Bone Marrow Transplantation Team.
AB  - We studied the impact of fluconazole prophylaxis (400 mg/day) on clinical
      features including fever and use of amphotericin in a randomized, double-blind,
      placebo-controlled (1:1 randomization) study among patients undergoing
      chemotherapy for leukemia and those undergoing bone marrow transplantation.
      Fluconazole or placebo was given throughout the period of neutropenia.
      Amphotericin was administered to 5 of 23 (22%) fluconazole recipients and 14 of
      23 (58%) placebo recipients (p < 0.01). Median duration of amphotericin used in
      fluconazole and placebo groups was 9 days (mean 10.8) and 13 days (mean 14)
      respectively. Patients who received fluconazole had significantly shorter
      duration of fever prior to treatment with amphotericin (days, median 5 vs. 9, p <
      0.05). Superficial fungal infections were noted in 8 (34%) fluconazole recipients
      and 19 (79%) placebo recipients (p = 0.002). Fluconazole was well tolerated.
      Prophylaxis with fluconazole resulted in a significant reduction in the empiric
      use of amphotericin, duration of fever and incidence of superficial fungal
      infections.

PMID- 8131636
TI  - Carboplatin and etoposide as outpatient treatment of advanced non-small-cell lung
      cancer.
AB  - Twenty-four outpatients with locally advanced (inoperable or unsuitable for
      radical radiotherapy) or metastatic non-small-cell lung cancer were treated with
      carboplatin (300 mg/m2 day 1)+etoposide (120 mg/2 day 1-3), every 3 weeks. Two
      patients died of disease progression before completing at least 2 cycles of
      chemotherapy. Four patients (16.7%) obtained a partial response, 10 had disease
      stabilization (41.7%) and 8 progressed (33.3%). Median overall survival was 8
      months (range 1-22). Toxicity was moderate, with no nephro-, neuro- or
      ototoxicity.

PMID- 8131637
TI  - Morphological alterations of Staphylococcus aureus and Streptococcus pyogenes
      exposed to cefdinir, a new oral broad-spectrum cephalosporin.
AB  - Affinity for penicillin-binding proteins (PBPs) and the morphological alteration
      of Staphylococcus aureus 209-P JC and Streptococcus pyogenes C-203 exposed to
      cefdinir were studied. Although cefdinir was bactericidal against both strains,
      the extent of the decrease in colony-forming units (CFU) was similar in a fairly
      wide range of concentrations. Transmission electron microscopy of S. aureus 209-P
      JC revealed that cefdinir induced thickening of the cross wall and frequent cell
      lysis at low concentrations. The lytic sites were seen at the site of septum
      formation. In S. pyogenes C-203, cefdinir induced thickening of the peripheral
      wall and cross wall, and protoplast-like cells were observed during the
      incubation period. Cefdinir showed high affinity for all PBPs of S. aureus 209-P
      JC and S. pyogenes C-203. The drastic changes in the morphology of S. aureus and
      S. pyogenes were caused by binding of cefdinir to all PBPs.

PMID- 8131638
TI  - In vitro activity of cefdinir (FK482) and ten other antibiotics against gram
      positive and gram-negative bacteria isolated from adult and pediatric patients.
AB  - The in vitro activity of cefdinir, an oral aminothiazolyl hydroxyimino
      cephalosporin was compared with that of cefixime, cefpodoxime, cefaclor,
      cephalexin, ciprofloxacin, ofloxacin, oxacillin, ampicillin, vancomycin and
      trimethoprim-sulfamethoxazole against 279 gram-positive and gram-negative recent
      clinical isolates from adult and pediatric patients. Cefdinir was the most active
      drug among the cephalosporins against oxacillin-sensitive Staphylococcus aureus
      and coagulase-negative staphylococci, Streptococcus pneumoniae, S. pyogenes,
      Escherichia coli and Moraxella catarrhalis (MIC90 0.015-2 mg/l). Cefixime was the
      most active agent against Hemophilus influenzae, Klebsiella pneumoniae, K.
      oxytoca, Proteus mirabilis and P. vulgaris (MIC90 < 0.015-0.125 mg/l). The
      activity of cefpodoxime was better than that of cefixime against S. pneumoniae
      and oxacillin-sensitive staphylococci (MIC90 0.25-8 vs. 0.5-32 mg/l), similar to
      cefixime against S. pyogenes (MIC90 0.06 mg/l) and not as good as cefixime
      against H. influenzae, M. catarrhalis, Klebsiella spp. and Proteus spp. (MIC90 <
      0.015-0.25 vs. 0.125-0.5 mg/l). The activity of cefdinir was greater than that of
      the other cephalosporins against Enterococcus faecalis (MIC90 16-32 vs. > 64
      mg/l). None of the cephalosporins were active against methicillin-resistant,
      coagulase-positive or -negative staphylococci or Pseudomonas aeruginosa (MIC90 >
      64 mg/l). Overall, the susceptibilities of adult and pediatric isolates were
      similar. Kinetic kill curves demonstrated rapid and similar killing at 6 h by
      cefdinir, cefixime, cefpodoxime and ofloxacin. At 24 h at 1 x MIC, the least
      regrowth was observed with cefdinir and cefpodoxime; at 2 x MIC, suppression of
      growth was similar with all four drugs.

PMID- 8131639
TI  - In vitro susceptibility of fungal isolates of clinically important specimens to
      itraconazole, fluconazole and amphotericin B.
AB  - The in vitro activity of itraconazole, fluconazole and amphotericin B was tested
      against 207 yeast strains and 3 Aspergillus fumigatus strains isolated from
      blood. The other 42 A. fumigatus strains were selected from respiratory tract
      infections. A microdilution method was employed to determine the inhibitory
      concentrations to restrain 70% of isolate growth (IC30). The inhibition
      concentrations of amphotericin B are all around the value 0.25 mg/l with a
      deviation of two concentration degrees, indicating sensitivity of all strains.
      The test results of itraconazole showed the majority of strains in the range of
      sensitivity (200 isolates) and low sensitivity (44 isolates). Five of 19 Candida
      glabrata strains demonstrated resistance to itraconazole. The results of
      fluconazole showed a good sensibility of C. albicans, but 4.5% of strains were
      resistant. Low sensitivity (1 strain) and resistance (24 strains) were evaluated
      for C. glabrata and C. krusei isolates. No strain of A. fumigatus was inhibited
      by fluconazole. The data show the necessity of in vitro tests.

PMID- 8131640
TI  - Enhanced susceptibility of Escherichia coli pretreated with RP7293 to leukocyte
      activity: comparison with other antimicrobial agents.
AB  - Antimicrobial agents may interact with polymorphonuclear leukocytes and directly
      modify the leukocyte functions, or bacteria can be modified by the antimicrobial
      agents causing them to be treated differently by phagocytic cells. Brief exposure
      of bacteria to high levels of antimicrobials can affect their interaction with
      leukocytes. The susceptibility of Escherichia coli to phagocytosis and killing by
      human polymorphonuclear leukocytes in the presence of normal human serum
      following treatment with RP7293, a new natural streptogramin, was examined, and a
      comparison made with clavulanic acid/amoxicillin, ciprofloxacin and fosfomycin.
      Pretreatment of E. coli for 10 min with 4 x MIC of RP7293 clearly sensitized the
      bacteria to leukocytic killing in the presence of normal human serum (10% v/v).

PMID- 8131641
TI  - Transfer in young children's understanding of spatial representations.
AB  - The creative and flexible use of symbols is a unique human ability. In order to
      use a symbol, one must understand the basic relation between the symbol and what
      it represents. How do young children come to appreciate such relations? One
      possibility is that insight into one symbolic relation helps children appreciate
      different ones. The 3 studies presented here support this possibility. In
      Experiments 1 and 2, both 2.5- and 3.0-year-old children showed transfer from an
      easy task that required appreciation of a model-room symbolic relation to a more
      difficult one, one that children their age typically do not appreciate. In
      Experiment 3, 2.5-year-olds showed transfer between symbol types: Experience with
      a model-room relation helped them appreciate a map-room relation. These transfer
      effects are consistent with the claim that early experience with symbolic
      relations contributes to symbolic sensitivity, a basic readiness to recognize
      that one object or event may stand for another.

PMID- 8131642
TI  - The relations of emotionality and regulation to children's anger-related
      reactions.
AB  - The purpose of this study was to examine the relations of emotionality (intensity
      and negative emotion) and regulation (attentional control, mode of coping) to
      preschoolers' naturally occurring anger reactions. School personnel's ratings of
      4-6-year-olds' constructive coping and attentional control were associated with
      boys' constructive anger reactions whereas their ratings of acting out versus
      avoidant coping, emotional intensity, and anger intensity generally were
      correlated with low levels of constructive reactions to anger. Mothers' reports
      of children's constructive coping and low emotional intensity were associated
      with children's use of nonabusive language to deal with anger, whereas aggressive
      coping and negative emotionality were associated with escape behavior when
      angered. The findings are consistent with the conclusion that individual
      differences in emotionality and regulatory skills are associated with children's
      constructive versus nonconstructive anger reactions.

PMID- 8131643
TI  - Being alone, playing alone, and acting alone: distinguishing among reticence and
      passive and active solitude in young children.
AB  - 3 forms of solitude were studied in young children--reticence (onlooker and
      unoccupied behavior), solitary-passive behavior (solitary-constructive and 
      exploratory play), and solitary-active behavior (solitary-functional and 
      dramatic play). 48 4-year-old children grouped in quartets of same-sex unfamiliar
      peers were observed in several situations. Mothers completed the Colorado
      Temperament Inventory. Results indicated that (1) solitary-passive, solitary
      active, and reticent behaviors were nonsignificantly intercorrelated; (2)
      reticence was stable and associated with the demonstration of anxiety and
      hovering near others, whereas solitary-passive and solitary-active play were
      stable yet unrelated to anxiety and hovering; (3) reticence during free play was
      generally associated with poor performance and displays of wariness in several
      other social situations, while solitary-passive and -active play were not; (4)
      reticence was associated with maternal ratings of child shyness, while solitary
      active behavior was associated with maternal ratings of impulsivity. Results are
      discussed in terms of the underlying mechanisms associated with reticence and
      passive and active withdrawal.

PMID- 8131644
TI  - Young children's comprehension of pretend episodes: the integration of successive
      actions.
AB  - In 3 experiments, children's comprehension of successive pretend actions was
      examined. In Experiment 1, children (25-38 months) watched 2 linked actions
      (e.g., a puppet poured pretend cereal or powder into a bowl, and then pretended
      to feed the contents of the bowl to a toy animal). Children realized that the
      pretend substance was incorporated into the second action. In Experiment 2,
      children (24-39 months) again watched 2 linked actions (e.g., a puppet poured
      pretend milk or powder into a container, and then pretended to tip the contents
      of the container over a toy animal). They realized that the animal would become
      "milky" or "powdery." In Experiment 3, children (25-36 months) drew similar
      conclusions regarding a substitute rather than an imaginary entity. The results
      are discussed with reference to children's causal understanding, their capacity
      for talking about objects and events in terms of their make-believe and real
      status, and the processes underlying pretense comprehension.

PMID- 8131646
TI  - Longitudinal assessment of autonomy and relatedness in adolescent-family
      interactions as predictors of adolescent ego development and self-esteem.
AB  - This study examined links between processes of establishing autonomy and
      relatedness in adolescent-family interactions and adolescents' psychosocial
      development. Adolescents in 2-parent families and their parents were observed in
      a revealed-differences interaction task when adolescents were 14, and
      adolescents' ego development and self-esteem were assessed at both 14 and 16.
      Developmental indices were strongly related to autonomy and relatedness displayed
      by both parents and adolescents. Significant variance was explained even after
      accounting for the number and quality of speeches of each family member as rated
      by a different, well-validated family coding system. Increases in adolescents'
      ego development and self-esteem over time were predicted by fathers' behaviors
      challenging adolescents' autonomy and relatedness, but only when these occurred
      in the context of fathers' overall display of autonomous-relatedness with the
      adolescent. The importance of the mutually negotiated process of adolescents'
      exploration from the secure base of parental relationships is discussed.

PMID- 8131645
TI  - The "little five": exploring the nomological network of the five-factor model of
      personality in adolescent boys.
AB  - The California Child Q-set (CCQ) was used to explore the structure of personality
      in early adolescence and to develop scales to measure the "Big Five" dimensions:
      Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to
      Experience. Mothers provided Q-sorts of 350 ethnically diverse boys between 12
      and 13 years old. Analyses of the construct validity of the scales provided a
      nomological network relating the Big Five to theoretically and socially important
      criterion variables, such as juvenile delinquency, Externalizing and
      Internalizing disorders of childhood psychopathology, school performance, IQ,
      SES, and race. These effects were obtained using diverse methods, including self
      reports from the boys, ratings by their mothers and their teachers, and objective
      test data. In addition to the Big Five, analyses also suggested 2 possibly age
      specific dimensions of personality in early adolescence. Discussion is focused on
      the changing manifestations of personality traits throughout development.

PMID- 8131647
TI  - Self-restraint as a mediator of family influences on boys' delinquent behavior: a
      longitudinal study.
AB  - In the course of social development, family influences seem to become partly
      internalized and transformed into personality characteristics that regulate
      behavior outside the family sphere. In a longitudinal study of 81 boys and their
      families, we hypothesized that individual differences in boys' self-restraint
      would serve as a mediator between family factors in preadolescence and sons'
      delinquent behavior 4 years later. Measures were derived from principal
      components analyses of multiple indices of each construct as assessed by multiple
      informants. As expected, parenting practices measured at both pre- and mid
      adolescence predicted delinquent acts only indirectly via their association with
      boys' self-restraint. In addition, general family functioning at preadolescence,
      independent of other scores, predicted boys' levels of self-restraint 4 years
      later. There was no evidence that boys' self-restraint at preadolescence
      systematically affected the quality of parenting that they subsequently received.
      Parents' and families' role in children's development of self-regulatory skills
      may be a primary vehicle by which they ultimately influence adolescents' problem
      behaviors.

PMID- 8131648
TI  - Socialization and family correlates of mental health outcomes among Hispanic and
      Anglo American children: consideration of cross-ethnic scalar equivalence.
AB  - Recently there has been concern over the need for developmental research within
      ethnic minority populations and interest in socialization and family variables
      within, and variability across, ethnic groups. This study reports analyses
      designed to: compare several socialization, family, and mental health variables
      among Hispanic and Anglo American 8-14-year-old children and mothers; examine the
      regression equations predicting mental health indicators with the socialization
      and family variables; and evaluate the cross-ethnic scalar equivalence of these
      socialization and family measures. The findings indicate that there are ethnic
      differences in several socialization and family variables; several of the
      socialization and family variables are related to the mental health variables,
      and these relations are very similar across ethnic groups; and the socialization
      and family measures appear to have sufficient cross-ethnic scalar equivalence for
      English-speaking, largely Mexican American Hispanic samples. Further, these
      findings suggest some caution regarding the use of the Child Depression Inventory
      in Hispanic samples.

PMID- 8131649
TI  - The relationship of maternal employment to early adolescent daily experience with
      and without parents.
AB  - This study examines how maternal work may shape pre- and young adolescents' daily
      life experience. According to the procedures of the Experience Sampling Method
      (ESM), 295 10-13-year-old children carried electronic pagers for 1 week and
      completed self-report forms in response to random signals sent every other hour.
      Their daily experience did not differ by maternal employment status, with the
      following exceptions: full-time maternal employment was associated with more time
      doing homework with mothers and less time in general leisure, while part-time
      employment was associated with more time doing sports with parents. Relative to
      those with nonemployed mothers, youth with part-time employed mothers reported
      more positive daily moods and higher self-esteem, while youth reported time with
      full-time employed mothers to be the friendliest. While children with employed
      mothers spent no less time with family, parents, friends, in class or alone, they
      spent more time alone with fathers.

PMID- 8131650
TI  - Parents' involvement in children's schooling: a multidimensional
      conceptualization and motivational model.
AB  - This study had 2 goals. The first was to examine a multidimensional
      conceptualization of parent involvement in children's schooling, defined as the
      allocation of resources to the child's school endeavors. A second goal was to
      evaluate a model in which children's motivational resources (i.e., perceived
      competence, control understanding, and self-regulation) are mediators between
      parent involvement and children's school performance. 300 11-14-year-old children
      and their teachers participated. Factor analyses of a set of parent involvement
      measures supported the hypothesized 3 dimensions of parent involvement: behavior,
      intellectual/cognitive, and personal. Path analyses revealed indirect effects of
      mother behavior and intellectual/cognitive involvement on school performance
      through perceived competence and control understanding, and indirect effects of
      father behavior on school performance through perceived competence. The results
      argue against a unidimensional understanding of parent involvement and support
      the view of the child as an active constructor of his or her school experience.

PMID- 8131651
TI  - Children's relationships with peers: differential associations with aspects of
      the teacher-child relationship.
AB  - Associations between children's social competence with peers and differential
      aspects of their teacher-child relationships were examined in a longitudinal
      sample of 48 4-year-old children enrolled in child care as infants. Toddler
      security with teacher was negatively associated with hostile aggression and
      positively with complex peer play and gregarious behaviors. Prosocial behaviors
      and withdrawing behaviors were associated with preschool security with teacher.
      Dependence on teachers as a preschooler was associated with social withdrawal and
      hostile aggression. Positive toddler teacher socialization was associated with
      higher perceived peer acceptance. Preschool teacher negative socialization was
      negatively associated with complex peer play, teacher ratings of hesitancy,
      friendly enactment, and accidental attribution and positively related to teacher
      ratings of difficulty.

PMID- 8131652
TI  - Maternal, teacher, and child care history correlates of children's relationships
      with peers.
AB  - Mother and teacher correlates of social competence with familiar and unfamiliar
      peers in 84 children who entered child care at three different times are
      examined. Social competence at age 4 was assessed with both familiar and
      unfamiliar peers. Relationships with both initial and 4-year-old teachers were
      related to social competence with peers. Maternal attachment relationships at 12
      months and at 4 years did not predict social competence with peers.

PMID- 8131653
TI  - Infantile amnesia: through a glass darkly.
AB  - Memory for former preschool classmates was examined in 9- and 10-year-old
      children using measures of both explicit and implicit memory. Yes-no recognition
      of faces was at low levels but was significantly above chance. Skin conductance
      data showed similarly low but above-chance differentiation between classmates and
      controls. A median split of children based on their recognition memory scores
      showed that children with little evidence of explicit memory for classmates were
      as likely to show differential skin conductance responding to faces of former
      classmates as were children with higher recognition scores. Infantile amnesia,
      like the clinical syndrome for which it is named, may not always involve complete
      loss of encoded information.

PMID- 8131654
TI  - The categorization of above and below spatial relations by young infants.
AB  - 3 experiments using the familiarization-novelty preference procedure were
      conducted to investigate whether 3-month-old infants could form categorical
      representations of the spatial relations above and below. In Experiment 1, one
      group of infants familiarized with exemplars depicting a dot in different
      positions above a horizontal bar displayed a subsequent visual preference for a
      novel category exemplar (dot below bar) that was paired with a familiar category
      exemplar (dot in novel position above bar). A second group of infants presented
      with exemplars in which the dot appeared in variable locations below the bar also
      responded preferentially to a novel category exemplar (dot above bar) when it was
      paired with a familiar category exemplar (dot in new position below bar). These
      preferences did not result from the salience of vertical up-down changes in dot
      position or the encoding of dot positions relative to an internal horizontal
      midline (Experiment 3) or from an inability to discriminate the members of each
      category (Experiment 2), but rather would seem to be a consequence of the ability
      to represent categorically the spatial relations above and below. The data
      provide evidence for early categorical organization in human spatial memory.

PMID- 8131655
TI  - Infants' instrumental use of their mothers to achieve their goals.
AB  - In order to investigate very young children's active contribution to managing
      interaction with others, we examined 6-13-month-old infants' instrumental use of
      their mothers to reach goals. We examined the idea that infants are already
      involved at 6 months in managing interaction with adults, with rapidly increasing
      instrumental use of mothers between 6 and 13 months. 64 mother-infant pairs were
      videotaped during structured episodes in which the investigator instructed the
      mother to challenge the infant to use her instrumentally to get access to or to
      work a toy. Already at 6 months of age, infants used their mothers instrumentally
      in 36% of the episodes. The amount of infants' instrumental use of their mothers
      increased to 67% of episodes at 9 months and continued increasing to 78% of the
      episodes by 13 months. These results suggest early and rapid development of
      infants' management of joint activities from as early as the middle of the first
      year of life.

PMID- 8131656
TI  - Event-related potentials in year-old infants: relations with emotionality and
      cortisol.
AB  - Event-related potentials (ERPs) were recorded from year-old infants presented
      with sets of familiar faces presented frequently and infrequently, and a set of
      novel faces presented infrequently. The normative response of infants in this
      sample was a late positive slow wave to the Infrequent Familiar faces, and a
      return to baseline to the Frequent Familiar and Infrequent Novel faces (although
      there was a tendency for some infants to show a positive slow wave to the latter
      events). A factor score based on data from frontal and central leads that
      reflected this normative pattern was significantly associated with infant
      emotional behavior and cortisol. Infants scoring higher on the normative ERP
      factor were more distressed during separation, were reported by their parents to
      smile and laugh more, and had lower cortisol concentrations during ERP testing.
      These data were interpreted as reflecting the coordination of adaptive responding
      among different physiological and behavioral systems.

PMID- 8131657
TI  - Quality of toddler-mother attachment in children with Down syndrome: limits to
      interpretation of strange situation behavior.
AB  - Researchers studying social-emotional development have argued that primary
      attachment relationships, established by the end of the first year of life, are
      important organizing factors that influence the trajectory of development
      throughout childhood. Central to this argument is a dimension of "attachment
      security," along which attachments differ. For normally developing infants and
      toddlers, attachment security is assessed using the Ainsworth Strange Situation.
      However, it is not clear that this procedure is appropriate for evaluating
      attachment security in atypical populations. In this report, 3 samples of
      children with Down Syndrome (total N = 138) were assessed using the Strange
      Situation. The procedures were scored according to traditional protocols.
      Although the 3 samples differed with respect to chronological and developmental
      age, they showed basic similarity with respect to attachment variables. However,
      developmentally younger children were more difficult to classify using the
      standard scoring rules. Scores and classifications for the sample were compared
      to scores from a sample of normally developing children tested at about 12 months
      of age. Significant differences with respect to the distributions of cases to
      classification categories and with respect to the interactive scale scores
      suggest that the Strange Situation may be measuring different aspects of behavior
      for children with Down Syndrome, even when they are tested at similar
      developmental age levels.

PMID- 8131658
TI  - [The influence of Chinese traditional medicine on the production and activity of
      interleukin 1 (IL-1)].
AB  - Interleukin 1 (IL-1) is a cytokine closely related to the pathogenesis of
      inflammation and chronic destructive changes in rheumatoid arthritis (RA).
      Analysis of the effect of antirheumatic drugs on IL-1 production and activity is
      of great importance in exploring the therapeutic mechanism of RA. The purpose of
      the present study was to investigate the effect of Chinese herbs (10 prescription
      and 15 single drugs), which was often used in the treatment of RA, on the
      production and activity of IL-1. The production of IL-1 was tested through human
      monocytes stimulated with zymosan and measured by ELISA method; the activity of
      IL-1 was measured by its effect on the proliferation of murine thymocytes. The
      results showed that Tripterygium Wilfordii Hook, Tripterygil Hyhoglauci
      Tetrandrine significantly inhibited both of IL-1 production and IL-1 activity;
      while Aconiti Tuber, Ephedrae Herba, Atractyloidis Rhizoma, Atractyloidis Lanceae
      Rhizoma, Ledebouiellae Radix slightly inhibited IL-1 activity but not affecting
      IL-1 production. The ten prescriptions had no inhibitory effect on both of IL-1
      production and IL-1 activity.

PMID- 8131659
TI  - [Seroepidemiological investigation on Japanese encephalitis in Taiwan (January
      1989-December 1991)].
AB  - The hemagglutination inhibition (HI) test was used to detect sero-confirmed cases
      of clinically suspected Japanese encephalitis. The results revealed a total of 76
      sero-confirmed cases; 24, 27 and 25 cases respectively for the year 1989, 1990
      and 1991. The percentages of sero-confirmed cases with respect to reported cases
      were 12.97%, 12.33%, 10.04% respectively. The mean percentage was 11.64%. The
      mean number of sero-confirmed cases in recent three years was 25, and morbidity
      rate per 100,000 population was 0.125. The number of sero-confirmed cases in 1970
      was 269, and morbidity rate per 100,000 was 1.86. The comparison of these two
      groups showed the ratio of 1:11 and 1:15. It demonstrated that the period of 50%
      sero-conversion of HI antibody positive pigs appeared two months earlier in the
      middle of May currently as against the middle of July during the years 1966-1968.
      The period of JE prevalence likewise shifted two months earlier to the months of
      May, June and July, with a peak in June in 1989-1991 as against the months of
      July, August and September with a peak in August in 1966-1968. There occurred a
      few sporadic cases in other months away from the period of major epidemic. With
      regard to the geographical distribution of the sero-confirmed cases in recent
      three years, most JE cases were detected in the Taipei basin and the Kaohsiung
      Pingtung river basin. The next numerous cases were found in the terrace which
      extends from Taoyuan, Hsinchu and Miaoli to the central Taiwan and in the Chiayi
      Tainan plain. Only four cases were reported from Ilan, Hualien and Taitung
      counties. During the years between 1955 and 1967, the vast majority of cases
      occurred among children, especially of 2-9 years of age. The next suffered group
      was the age group of 10-14 years. In the meanwhile, the current major group of
      victim was the age group of 10-14 years and its morbidity rate per 100,000
      population was 0.30. The second suffered group was the age group of 20-24 years
      and its morbidity rate was 0.28, and the third was the age group of 0-9 years and
      its morbidity rate was 0.16. The percentages of sero-confirmed cases of the above
      each age group with respect to all sero-confirmed cases were 23.68%, 21.05%,
      22.36% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8131660
TI  - Crusted scabies in systematic lupus erythematosus: a case report.
AB  - Crusted scabies (Norwegian scabies) is uncommon in clinical practice and may
      present as papulosquamous dermatosis. A case of crusted scabies in systemic lupus
      erythematosus (SLE) is described. The skin lesions simulated those of subacute
      cutaneous lupus erythematosus of the papulosquamous type, and became the source
      of epidemic scabies in the hospital. The colonization with Staphylococcus aureus
      within crusted lesions may have contributed to the patient's sepsis. This case
      illustrates the pitfalls in recognition of crusted scabies and the importance of
      rapid diagnosis.

PMID- 8131661
TI  - Non-excretory myeloma with diffuse osteolytic lesions caused by tumor necrosis
      factor: report of a case.
AB  - A 63-year-old male patient was admitted to the hospital after a six-month
      complaint of low back pain. Anemia, hypercalcemia and 5 to 18% giant abnormal
      binucleated plasma cells infiltrations in the bone marrow suggested a diagnosis
      of multiple myeloma. However, repeated serum and urine immunofixation
      electrophoresis failed to demonstrate any abnormal monoclonal band. Diagnosis of
      non-excretory myeloma was verified by immunocytochemical stains demonstrating
      intracellular kappa chain in these neoplastic cells. Some authors have claimed
      that there were fewer bone lytic changes, less bone marrow infiltration, more
      preservation of normal immunoglobulin but with more neurological presentations
      among non-excretors. However, this patient had severely generalized bone lytic
      lesions and high serum level of tumor necrosis factor. The former might be
      attributed to the latter. Literatures about multiple myeloma and the tumor
      necrosis factor are also reviewed.

PMID- 8131662
TI  - Detection and identification of toxigenic Vibrio cholerae O1 strains by a
      simplified polymerase chain reaction method.
AB  - The polymerase chain reaction (PCR) with three oligonucleotide primers was used
      to amplify both 184 bp and 425 bp DNA fragments of cholera toxin A subunit gene
      (ctxA) for detection and identification of toxigenic V. cholerae O1 strains in
      one step. For enhancing the sensitivity, we have used the chemiluminescent
      detection system for Southern hybridization. A total of 92 Vibrio strains were
      tested by both PCR and enzyme-linked immunosorbent assay (ELISA). Three E. coli
      (ETEC) strains, one toxigenic V. mimicus, and one toxigenic V. cholerae non-O1
      were also tested for cross reactivities. Our results indicated that the
      correlation between the immunological ELISA method and the molecular biological
      PCR method were very well. The lowest detectable amount of the purified serotype
      Inaba chromosomal DNA by PCR is 2 pg and 0.4 pg by chemiluminescent detection
      system. In this work we report a PCR assay with a combination of three primers to
      detect and identify the ctxA of V. cholerae O1 in one step. The simplified and
      accurate method is useful for toxigenic V. cholerae O1 detection and
      identification.

PMID- 8131663
TI  - A lady and chronobiology.

PMID- 8131664
TI  - Circadian variations in psychological measures: a new classification.

PMID- 8131665
TI  - Spectral analysis of circadian rhythm data: an application in Acetabularia.

PMID- 8131666
TI  - Study of seasonal behavior in erythrocyte sedimentation rate (ESR).
AB  - The ESR is used as a common human clinical laboratory test which allows
      identification in the presence and intensity of active pathologies. In this
      paper, the seasonality of the variable was described and modelled. Monthly means
      and medians of a transformation of this variable were used. Nonparametric
      smoothing techniques and cumulative periodograms permitted to describe the
      seasonal behavior, and parametric models allowed to demonstrate its significance.

PMID- 8131667
TI  - Power of 'phase 0' chronobiologic trials at different signal-to-noise ratios and
      sample sizes.
AB  - Clinical trials would gain from incorporating 'Phase 0' chronobiologic pilot
      designs both from the viewpoint of (statistical) power and cost-effectiveness.
      Herein, this statement is documented by power computations and is further
      illustrated by clinical examples answering specific questions. Power computations
      show the merits both of chronobiologic designs (that assign samples at
      equidistant intervals to cover one full cycle of anticipated pertinent rhythms)
      and of chronobiologic analyses (the cosinor versus the analysis of variance).
      Randomized clinical trials would gain from incorporating a concern for timing as
      well as dosing in all three stages of clinical trials (Phase I, II and III
      focusing on toxicity, efficacy and a comparison with the current best treatment,
      respectively) and could be cost-effectively preceded by 'Phase 0' trials so as to
      detect, sooner and with smaller sample sizes, desired or undesired effects that
      may otherwise be missed.

PMID- 8131668
TI  - Gain in power from chronobiologic designs and analyses.

PMID- 8131669
TI  - Clinical trials: the larger the better?
AB  - A chronobiologic approach is much more than fine-tuning that may perhaps be
      considered after a drug has been identified as useful; at very little cost at
      first, a Phase 0 chronobiologic trial may show that there is danger that a given
      drug may do more harm than good when administered at the wrong time. At least
      equally important, the chronobiologic approach may recognize the usefulness of a
      drug that is active only at the proper time. When different chronobiologic timing
      results in opposite effects from the same total weekly dose of the same drug, it
      is clear that timing cannot be separated from dosing. The time structure-adjusted
      pattern of drug administration can make the difference between the undesired
      stimulation of a malignant growth and shortening of survival time and the desired
      growth inhibition and prolongation of survival. The experience with lentinan,
      namely that this immunomodulating drug can stimulate as well as inhibit the
      development of a cancer, may apply to many more therapeutic agents in a day and
      age of biologic response modifiers. It is a point of particular importance that
      an immunostimulator ought not be given at a time when it can be an
      immunosuppressor. What is surprising to many under these circumstances is that
      chronobiologic designs are also cost-effective. Most scholars believe that if a
      test is carried out at six times, it will cost six times more, will require six
      times more patients and six times more work. We believe we have shown that the
      reverse holds true: if so, the discussion of the pros and cons of chronobiometry
      and of neglect thereof becomes one of ethics. Figures 1-5 depict the status quo.
      Examples have been given to show that some effects can be obtained only at
      certain times with the dose used. Figure 8 reveals the doubling of the desired
      anticancer effect by timing treatment according to an unspecific marker rhythm.
      The recognition of the power of chronobiologic designs coupled to the discovery
      of large-amplitude rhythms in non-invasively determined marker chronomes is a
      challenge that can be exploited, particularly in the treatment of cancer. Marker
      determinations are still expensive, but once the cost of their development is
      paid, a market is established, and the community is trained in self-help, the
      responsibility now assumed by most diabetic patients for themselves can also be
      shouldered by cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8131670
TI  - Power of chronobiologic pilots: a statistician's opinion.

PMID- 8131671
TI  - Circadian cortisol rhythm of rabbits kept on different lighting regimens.

PMID- 8131672
TI  - Circadian variations of self-reported activation: a multidimensional approach.
AB  - Self-reported activation measures through adjective checklist have not been
      widely tested in the field of chronopsychology. Previous studies have mostly
      explored two daily measurements (morning/evening) and reported differences as a
      function of the time of day. The aim of this study is to determine whether the
      energetic arousal, tensional arousal and hedonic tone scales of the Matthews'
      inventory (UMACL) change the function according to the time of day (09(00),
      13(00), 17(00) and 21(00)). We also test whether morningness, sex or personality
      factors influence the results. The sample consisted of 156 university students of
      age 17-28 years, 41 of whom were men and 115 women. When all the subjects are
      considered, all UMACL scales show significant differences according to the time
      of day. Subjects presented a fall in their energetic arousal and hedonic tone
      from morning to evening, while tensional arousal increased throughout the day.
      However, when individual differences are taken into account, only morningness
      influences energetic arousal and hedonic tone. Morning-type subjects show an
      earlier peak time than evening-type subjects in both scales. The use of adjective
      checklist measures has been shown to be a valid method of revealing Self-reported
      circadian variations, and to assess individual differences in terms of their
      circadian typology or morningness.

PMID- 8131673
TI  - More on the dentist's role in the prevention of high blood pressure.

PMID- 8131674
TI  - Pyrrhocoris apterus (L.) chronome's response to lighting may reveal changes in
      rhythms that switch developmental pathways.

PMID- 8131675
TI  - Untenable acceptance of casual systolic/diastolic blood pressure readings below
      140/90 mmHg.

PMID- 8131676
TI  - Core temperature rhythms in normal and tumor-bearing mice.
AB  - The core temperature temporal behavior of DBA/2 mice (11 normal and 13 with an
      ascites tumor) was studied using surgically implanted radio telemetry
      transmitters. Normal mice continuously displayed a stable 24 hour temperature
      rhythm. Tumor-bearers displayed a progressive deterioration of the temperature
      rhythm following inoculation with tumor cells. While such disruptions have been
      noted by others, details on the dynamics of the changes have been mostly
      qualitative, often due to time-averaging or steady-state analysis of the data.
      The present study attempts to quantify the dynamics of the disruption of
      temperature rhythm (when present) by continuously monitoring temperatures over
      periods up to a month. Analysis indicated that temperature regulation in tumor
      bearers was adversely affected during the active period only. Furthermore, it
      appears that the malignancy may be influencing temperature regulation via
      pathways not directly attributable to the energy needs of the growing tumor.

PMID- 8131677
TI  - Chronobiologic perspective of international health care reform for the future of
      children.
AB  - The realization of the implications of splitting the atom ended a tragic war. The
      nuclear age ensued. Likewise, a devastating escalation of health care costs could
      be ended by realizing the implications of splitting the normal range. Our
      currently disease-cure-oriented health care system does too little too late.
      Chronobiology could change this status quo into a system that recognizes risk
      early; it would gain new information from the resolution of predictable
      variations that take place within the physiologic range. Investment into
      vaccinations leads to returns in the form of savings in suffering and cost. A
      relatively modest investment into a 'Blood Pressure Health Start', pursued while
      chronobiology is being taught as an integral part in primary, secondary, higher
      and continued education, may not only drastically and in some respects promptly
      reduce the health care bill, but it would help the economy of the country that
      invests into the development of instrumentation for a chronobiologic systems
      approach. On the one hand, reducing the number of cases of catastrophic diseases,
      via improved diagnosis (to start with) of the blood pressure status, is likely to
      substantially reduce the budget deficit by reducing the legitimate and essential
      costs of care (to start with, of strokes and heart attacks, that kill more people
      than all other diseases combined and that have blood pressure disorders as their
      major risk factor). On the other hand, by implementing a novel health care system
      which also involves new technology that can become in demand worldwide, any trade
      balance will be improved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131678
TI  - A response to the health care crisis: a 'health start' from 'womb to tomb'.

PMID- 8131679
TI  - Evaluation of colonic sensory thresholds in IBS patients using a barostat.
      Definition of optimal conditions and comparison with healthy subjects.
AB  - To study the role of abnormal visceral perception in the pathophysiology of the
      irritable bowel syndrome (IBS), we evaluated colonic tone and visceral perception
      during intracolonic distension using a flaccid balloon connected to a
      computerized barostat and placed in the descending colon of IBS patients and
      healthy controls. In the first part of the study, basal colonic tone and response
      to pharmacological (neostigmine and glucagon) and physiological (1000-kcal meal)
      stimuli were recorded in nine IBS patients. Colonic tone increased by 72 +/- 27%
      after injection of neostigmine and decreased by 88 +/- 62% after glucagon. After
      the meal, the maximal increase in colonic tone was 76 +/- 31% with the total
      response to the meal lasting 109.7 +/- 32.0 min. In the second part of the study,
      symptomatic responses (discomfort and pain thresholds) and pressure variations
      were evaluated during two different methods of distension (stepwise and
      intermittent) in a randomized order in the nine IBS patients and six healthy
      controls. Each distension method was repeated twice in IBS patients to study
      reproducibility. In IBS patients, the mean discomfort threshold volume was 172 +/
      76 ml when using stepwise and 167 +/- 43 ml when using intermittent distension.
      The mean pain threshold volume was 250 +/- 25 ml when using stepwise and 211 +/-
      22 ml when using intermittent distension, this difference being statistically
      significant (P < 0.02). Discomfort and pain threshold volumes recorded during the
      first session of the same distension method were not different from those
      recorded during the second one.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131681
TI  - Nd:YAG laser in treatment of rectal cancer. Are there features predicting a
      curative result?
AB  - In the present study we report the results of Nd:YAG laser treatment in 36
      patients with rectal carcinoma in whom negative biopsies were obtained at the end
      of the treatment. The laser (100-W maximal power output) was applied through a
      flexible endoscope during 20- to 40-min sessions repeated every three days until
      the lesion was destroyed completely. Follow-up examinations, including endoscopy
      with biopsies, liver and endorectal ultrasonography and chest x-ray were
      performed every three months during the first year and thereafter once a year.
      Between 1980 and 1991, 272 patients were treated. All were unfit for surgery
      because of metastasis (78), recurrence after an other procedure (54), associated
      conditions, or old age (140). No circumferential tumors of any size were
      obliterated, but among the 139 patients presenting with a noncircumferential
      lesion less than 7 cm in diameter, negative biopsies were obtained after laser
      treatment in 36 patients (26%). Of these 36 patients, eight had been treated
      previously by surgery (5) or radiotherapy (3). Mean follow-up is 37 months (range
      12-71). Recurrences were observed in four cases. Seven patients died during the
      study but only one death was related to the cancer (pelvic extension 19 months
      after treatment). Endorectal ultrasonography was performed prior to treatment in
      15 patients and showed no invasion of the rectal wall deeper than the submucosa.
      After treatment, endorectal ultrasonography in 22 patients showed significant
      changes corresponding to cicatricial pattern in 60% of controlled
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131680
TI  - Protein kinase C activity as a potential marker for colorectal neoplasia.
AB  - Protein kinase C (PKC) is a mediator of transmembrane signal transduction,
      important in cell growth and differentiation. Cell activation by extracellular
      signals is associated with a translocation of PKC from the cytosol to the
      membrane. We measured and compared PKC activity in cytosol and membrane fractions
      of normal and neoplastic colorectal tissue. Total and membrane-associated PKC
      activity in normal colorectal tissue was greater in patients (N = 16) with
      colorectal cancer compared to that from patients with a normal colonoscopy (N =
      16), P < 0.01. A similar trend was noted in PKC activity of normal colorectal
      tissue from patients with adenomas compared to patients with a normal
      colonoscopy. PKC activity (total, membrane-associated, percent membrane) was not
      different in neoplastic colorectal tissue compared to that of adjacent normal
      tissue. However, there was a considerable range of PKC activity noted in all
      groups, which would limit the utility of PKC activity as a marker for colorectal
      neoplasia.

PMID- 8131682
TI  - Safety and clinical efficacy of flexible sigmoidoscopy and colonoscopy for
      gastrointestinal bleeding after myocardial infarction. A six-year study of 18
      consecutive lower endoscopies at two university teaching hospitals.
AB  - The risks versus benefits of flexible sigmoidoscopy and colonoscopy performed
      within three weeks of myocardial infarction were studied in nine consecutive
      patients who underwent sigmoidoscopy and in nine consecutive patients who
      underwent colonoscopy at two university hospitals. Indications for sigmoidoscopy
      were red blood per rectum in seven and occult blood in the stools in two.
      Sigmoidoscopy provided the diagnosis in three, including colon cancer in two and
      bleeding internal hemorrhoids in one, and provided helpful information in three.
      Sigmoidoscopy led to colon cancer surgery in two patients, and polypectomy of a 1
      cm adenoma in one. Of two highly unstable patients before sigmoidoscopy, one
      developed second-degree heart block and frequent premature ventricular
      contractions 3 hr after sigmoidoscopy. No sigmoidoscopic complications occurred
      in the seven relatively clinically stable patients. Indications for colonoscopy
      included red blood per rectum in five, occult blood in the stools in three, and
      melena in one. Colonoscopy provided the diagnosis in five, including one each
      with colon cancer, internal hemorrhoids, large adenoma, ischemic colitis, and
      angiodysplasia. Colonoscopy resulted in colon cancer surgery in one patient and
      endoscopic polypectomies in three patients. Of two moderately unstable patients
      before colonoscopy, one developed asymptomatic bradycardia during colonoscopy. No
      colonoscopic complications occurred in the seven clinically stable patients. This
      study suggests that recent myocardial infarction is not an absolute
      contraindication to sigmoidoscopy or colonoscopy, that sigmoidoscopy is
      beneficial in medically stable patients with significant gastrointestinal
      bleeding, and that colonoscopy may be beneficial in selected, highly stable
      patients with significant gastrointestinal bleeding.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8131683
TI  - Loss of protein kinase C delta isozyme immunoreactivity in human adenocarcinomas.
AB  - Protein kinase C (PKC) has been implicated in the control of colonic epithelial
      proliferative activity and in the process of malignant transformation. In the
      present study, we assessed by histone IIIS phosphorylation in vitro, total PKC
      activity, and the subcellular distribution of this activity in human
      adenocarcinomas and surrounding uninvolved mucosa from six patients. In these
      same tissues, we also examined the isozyme profile of PKC by immunoblotting.
      Total PKC activity and the subcellular distribution of PKC activity was not
      significantly different in mucosa compared to corresponding values in the tumors.
      Extracts of both human mucosa and tumors reacted with antibody to PKC isozymes
      alpha, beta, delta and zeta but did not react with antibody to the gamma and
      epsilon isozymes. The antibodies employed were directed against rabbit brain PKC
      (alpha, beta, gamma) or peptide sequences deduced from rat cDNA (gamma, delta,
      epsilon, and zeta). Accordingly, the apparent absence of the epsilon isozyme in
      human mucosa and adenocarcinoma may be due to failure to conserve the relevant
      sequence rather than to loss of the isozyme per se. No statistically significant
      differences were noted in subcellular distribution of any of the isozymes in the
      tumors compared to mucosa. However, the subcellular distribution of the delta
      isozyme was highly variable in the tumors. Total PKC beta immunoreactivity and
      that of the soluble, but not particulate, fraction were both significantly lower
      in homogenates of adenocarcinomas compared to corresponding values in surrounding
      mucosa, when expressed as a function of protein. However, these differences in
      PKC beta were abolished when results were expressed as a function of tissue DNA
      content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131684
TI  - Effect of human bowel wall distension on translocation of indigenous bacteria and
      endotoxins.
AB  - The effect of colonic distension on the translocation of indigenous bacteria and
      endotoxins was prospectively assessed in 50 consecutive patients undergoing
      colonoscopy. Semiquantitative bacteriologic cultures, chromogenic LAL testing for
      endotoxemia, and serial determinations of inflammatory markers were used. At the
      end of the endoscopic procedure, true bacteremia was found in only two patients
      with obstructing colorectal cancer. There was no evidence of systemic endotoxemia
      either being induced or increased during the observation period. The endotoxin
      detoxifying plasma capacity was elevated in patients with preexisting
      inflammation and did not change within this period. Levels of TNF-alpha,
      interleukin-6 (IL-6), and elastase (E alpha 1PI) did not differ from baseline
      values. C3 alpha levels increased in 20% of the patients, whereas fibrinopeptide
      A values rose by up to 10(2) during colonoscopy. However, since neither
      endotoxin, TNF alpha, nor IL-6 levels were found to be elevated in this study,
      the excessive activation of the coagulation system must be related to the
      distension of bowel wall vessels rather than to an effect of endotoxins escaping
      from the lumen.

PMID- 8131685
TI  - Study of constancy of hydrogen-consuming flora of human colon.
AB  - The constancy of the hydrogen consuming flora of the human colon was studied in
      15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen
      disappearance rate and the major products of H2-consuming bacteria, methane and
      sulfide, were measured during incubation of fecal homogenates with excess
      hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant
      hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither)
      remained constant. However, major shifts in these pathways were observed in four
      subjects, with two losing and two gaining the ability to produce methane.
      Methanogenesis was associated with the highest hydrogen consumption rate. This
      study demonstrates that clinically unrecognizable, major alterations of the
      colonic flora occur in healthy subjects. Understanding of the factors responsible
      for these alterations might allow for therapeutic manipulation of the colonic
      flora.

PMID- 8131686
TI  - Fecal excretion of alpha 1-antitrypsin in patients with Crohn's disease. A
      comparison of nephelometry and radial immunodiffusion.
AB  - A comparison is made of two methods for quantifying fecal alpha 1-antitrypsin
      (A1ATF): nephelometry (NPL) (the method habitually employed in our laboratory),
      and radial immunodiffusion (RID). A method is also described for extracting A1ATF
      from single 24-hr stool samples. The normal A1ATF values were initially
      established in 25 healthy controls, followed by quantification of the protein in
      30 patients with Crohn's disease, with the aim of evaluating the sensitivity and
      specificity of the test in assaying A1ATF and alpha 1-antitrypsin fecal clearance
      (CLAT). The precision of the measurement method and its applicability to the
      A1ATF extraction process are also evaluated. The ranges of normal A1ATF and CLAT
      values were found to be 0-42.2 mg/24 hr and 0-12.6 ml/24 hr, respectively;
      sensitivity was in turn 83% and 80% for A1ATF and CLAT, respectively, with a
      specificity of 100% in both cases. A good correlation was observed between the
      A1ATF quantifications afforded by RID and NPL in both the controls and patients
      with Crohn's disease (r = 0.917 and 0.997, respectively). We consider that A1ATF
      quantification is a rapid, safe, and reproducible method that is well tolerated
      by the patient.

PMID- 8131687
TI  - Mast cells are not essential to inflammation in murine model of colitis.
AB  - A simple rat model of chronic intestinal inflammation was adapted to mice in
      order to ascertain whether mast cells play an essential role in its induction or
      perpetuation. Colitis was induced in C57BL mice by intrarectal administration of
      trinitrobenzene sulfonic acid in 50% ethanol. Higher doses of trinitrobenzene
      sulfonic acid per gram of body weight were required in mice than rats, with a
      narrower effective dose range (the upper dose limited by unacceptable mortality
      and the lower by decreased inflammation). Colons of treated mice were
      macroscopically inflamed, with transmural damage, adhesions to adjacent
      structures, and ulcerations. Inflammation was scored subjectively and by tissue
      weight and myeloperoxidase content; each index was increased dose-dependently by
      trinitrobenzene sulfonic acid doses of 0.3-10 mg. Six milligrams of
      trinitrobenzene sulfonic acid induced reproducible inflammation for up to four
      weeks. Trinitrobenzene sulfonic acid could induce inflammation in both mast-cell
      deficient W/Wv mice and their normal +/+ littermates in a similar fashion. Thus
      it is possible to induce chronic colitis in the mouse. Mast cells are not
      essential participants in this process.

PMID- 8131688
TI  - Study of colonic IgG Fc binding site in cultured epithelial cells.
AB  - Previously, we identified a unique binding site for the Fc region of IgG in
      goblet cells of the human small intestine and colon. Understanding of the
      regulation and biological role of the binding site would be enhanced if it could
      be studied in cultured cells. Thus, we now have searched colonic carcinoma cell
      lines for presence of the site and further characterized it in such cells. HT29
      and HT29-18N2 (a mucin-secreting subclone) cells were capable of binding IgG. The
      binding was associated with mucus-producing cells only in the cultures, was
      enhanced by culture of the cells in galactose-containing medium (which favors
      mucin production) as compared to glucose-containing medium, and was much greater
      for the HT29-18N2 cells than for the HT29 cells. LS 174T cells did not bind IgG
      despite the presence of numerous mucin-containing cells, and Colo 205 and LoVo
      cell cultures had neither mucin-containing cells nor IgG binding; thus, IgG
      binding and mucin production are not inseparably linked. By use of monoclonal
      antibodies to three different molecular-size components of the binding site, we
      found that a > 200-kDa component probably is necessary but not sufficient for IgG
      binding, whereas 78-kDa and 110- to 140-kDa components are not necessary.

PMID- 8131689
TI  - A vascular hypersensitivity model of acute multifocal gastrointestinal
      infarction.
AB  - We have investigated the hypothesis that submucosal vasculitis may account for
      the patchy transmural inflammation observed in Crohn's disease. Test ferrets (N =
      11) were sensitized to human albumin. Five days after the last sensitization
      injection, human albumin microspheres (15-150 microns diameter) were injected
      intraarterially into the mesenteric circulation of a defined loop of mid-gut. Six
      control ferrets showed no histological abnormality at either 48 hr or two weeks
      after intraarterial injection. At 48 hr, five of six presensitized ferrets
      demonstrated submucosal vasculitis with fibrinoid necrosis. In two cases there
      was transmural inflammation and mucosal ulceration. A further five presensitized
      ferrets received weekly subcutaneous human albumin injections following the
      mesenteric intraarterial injection of albumin microspheres: after two weeks one
      animal demonstrated mild perivascular inflammatory changes and another
      demonstrated vasculitis. One of the two animals with transmural inflammation and
      mucosal ulceration at 48 hr, and the animal with vasculitis at two weeks, had
      precipitating antibodies to human serum albumin. This model demonstrates that an
      immune-mediated submucosal vasculitis can sometimes result in discontinuous
      transmural inflammation of the intestinal wall.

PMID- 8131690
TI  - Mucosal glucosamine synthetase activity in inflammatory bowel disease.
AB  - Abnormalities in colonic glycoprotein synthesis have been implicated in the
      pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is
      the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and
      has been measured in control subjects (N = 23) and patients with ulcerative
      colitis (N = 26) or Crohn's disease of the colon (N = 20) classified according to
      the macroscopic status of the rectum. Glucosamine synthetase activity was
      relatively constant around the normal colon but lower levels were found in the
      terminal ileum. In ulcerative colitis, glucosamine synthetase activity was
      similar to controls (24.0 +/- 1.9) mmol/g wet (wt/hr) irrespective of disease
      activity (quiescent: N = 13, = 27.3 +/- 1.9; active N = 16, = 26.2 +/- 2.3).
      Rectal glucosamine synthetase activity was normal in the presence of active
      Crohn's proctocolitis (29.4 +/- 3.1) but raised in patients with Crohn's colitis
      and rectal sparing (37.2 +/- 4.9 P < 0.02). Glucosamine synthetase activity was
      strongly influence by the degree of epithelial preservation.

PMID- 8131691
TI  - Respiratory burst of circulating polymorphonuclear leukocytes and plasma elastase
      levels in patients with inflammatory bowel disease in remission.
AB  - The activation of circulating polymorphonuclear leukocytes was determined in
      terms of superoxide radical generation and granulocyte elastase release in
      untreated patients with ulcerative colitis (N = 10) and Crohn's disease (N = 9)
      in remission and in control subjects (N = 10). Superoxide radical generation was
      determined by monitoring spectrophotometrically the reduction of ferricytochrome,
      after stimulation of cells with phorbol myristate acetate. Plasma elastase
      concentration was measured by a solid-phase enzyme immunoassay technique as the
      complex with alpha-1-proteinase inhibitor. Superoxide formation by
      polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's
      disease was significantly lower compared with controls [median (range)
      nmol/min/mg protein: Crohn's disease 7.8 (7.1-9.6); ulcerative colitis 8.25 (7.4
      10.3); controls 14.7 (13.6-15.8)] (P < 0.001), while no difference was found
      between the two groups of patients. In contrast plasma elastase levels in
      patients with ulcerative colitis and Crohn's disease were similar to that of
      controls. This defective respiratory burst of polymorphonuclear leukocytes in
      patients with inflammatory bowel disease in remission, in absence of an altered
      degranulation, could represent an important factor for the pathogenesis of these
      diseases.

PMID- 8131692
TI  - Childhood infections and the risk of inflammatory bowel disease.
AB  - Adults with inflammatory bowel disease from North Carolina were questioned during
      1986 and 1987 to assess risk due to a variety of childhood infections and
      treatments with antibiotics. Responses were compared with those of neighbor
      controls. Persons with Crohn's disease were more likely to report an increased
      frequency of childhood infections in general (odds ratio 4.67, 95% CI 2.65-8.23)
      and pharyngitis specifically (odds ratio 2.14, 95% CI 1.30-3.51). This was
      validated by an increased frequency of tonsillectomy (odds ratio 1.53, 95% CI
      1.07-2.20). Crohn's cases were more likely to report frequent treatment with
      antibiotics for both otitis (odds ratio 2.07, 95% CI 1.03-4.14) and pharyngitis
      (odds ratio 2.14, 95% CI 1.20-3.84). Although Crohn's cases were more likely to
      report frequent exposure to penicillin (odds ratio 1.81, 95% CI 0.98-3.31), there
      did not appear to be excess risk conferred by penicillin after controlling for
      frequency of infections. Persons with ulcerative colitis also reported an excess
      of infections generally (odds ratio 2.37, 95% CI 1.19-4.71), but not an excess of
      specific infections or treatments with antibiotics. Persons who reported an
      increased frequency of infections tended to have an earlier onset of Crohn's
      disease (P < 0.0001) and ulcerative colitis (P = 0.04). Finally, it was noted
      that urban living in childhood increased the risk for Crohn's disease. We
      conclude that childhood infections may be a risk factor for Crohn's disease and
      may presage the early onset of disease.

PMID- 8131693
TI  - Long-term follow-up of children with chronic idiopathic constipation.
AB  - To determine the outcome of chronic idiopathic constipation, we followed 62
      children with chronic idiopathic constipation (mean age: 5.2 +/- 2.8 years) for a
      period of five years. Each child received the same initial treatment over a 12
      week period and was then followed every three months. After five years from
      diagnosis, chronic idiopathic constipation persisted in 52% of the children; 47%
      who remained symptomatic were > 10 years old at the time of the five-year
      evaluation. Of the 27 who were constipated in the first year of life, 63%
      remained constipated after five years. Children who recovered within the five
      year interval were significantly different from those that remained symptomatic
      in age of onset of constipation (P < 0.05) and family history of constipation (P
      < 0.05). After five years, both severity of abdominal pain and degree of soiling
      significantly decreased in both the recovered and unrecovered groups (P < 0.05).
      This study suggests that chronic idiopathic constipation persists for > or = 5
      years in at least half of children. Early age of onset and family history of
      constipation are predictive of persistence. Abdominal pain and soiling improve in
      long-term follow-up irrespective of constipation outcome.

PMID- 8131694
TI  - Gastrobiliary motility after liquid fatty meal in progressive systemic sclerosis.
      A sonographic study.
AB  - Gastric emptying, antral motility, and gallbladder emptying after a liquid fatty
      meal were studied by ultrasound in 25 patients with progressive systemic
      sclerosis and in 25 sex- and age-matched controls. In patients with systemic
      sclerosis, the possible role of autonomic dysfunction was evaluated by four
      noninvasive cardiovascular reflex tests. Despite a significant delay of gastric
      emptying and a significant postprandial antral hypomotility in the patients with
      systemic sclerosis, the fat-induced gallbladder emptying was only slightly
      reduced, reaching no significant level when compared to the controls. The
      prolongation of gastric emptying correlated significantly with the duration of
      the disease. Although 36% of the patients in the systemic sclerosis group
      exhibited signs of autonomic cardiac dysfunction, there was no evidence of an
      association between these signs and gastric motor dysfunction. In conclusion
      motility disorders of the gallbladder seem to play a minor role in the upper gut
      involvement of systemic sclerosis, whereas motility disorders of the stomach are
      frequent and can be easily recognized noninvasively by real-time ultrasound.

PMID- 8131695
TI  - Relation between gastric emptying of albumin-dextrose meals and cholecystokinin
      release in man.
AB  - The effect of intragastric dextrose on albumin-stimulated cholecystokinin (CCK)
      release was studied in five healthy subjects and was related to gastric emptying
      and pancreatobiliary secretions. When combined with low concentrations of
      dextrose (4 g/100 ml), a 500-ml solution of albumin (7 g/100 ml) was rapidly
      emptied from the stomach into the duodenum (T1/2: 35 min). This rapid gastric
      emptying resulted in an only transient stimulation of pancreatobiliary secretion
      and an integrated CCK release of 278 +/- 45 pM x 180 min. When the concentration
      of dextrose in the albumin solution was increased from 4 g/100 ml to 21 g/100 ml,
      gastric emptying rate was distinctly slower (T1/2: 78 min; P < 0.01) and
      pancreatobiliary secretions became sustained (P < 0.01). CCK release was markedly
      higher (900 +/- 421 pM x 180 min; P < 0.05) after ingestion of the solution
      containing a high dextrose concentration. Intraduodenal infusion of 21 g/100 ml
      dextrose (3.1 ml/min) failed to significantly stimulate plasma CCK levels (119 +/
      38 pM x 120 min). We suggest that the higher CCK release in response to
      intragastrically administered albumin solution containing high concentrations of
      dextrose may have been induced by augmented peptic digestion of albumin due to
      delayed gastric emptying and by increased enteral digestion of albumin due to
      increased pancreatobiliary outputs.

PMID- 8131696
TI  - Pyloric motility. Sleeve sensor versus strain gauge transducer.
AB  - Intraduodenal infusion of nutrients has been shown by intraluminal sleeve
      sidehole manometry to suppress antral contractions and stimulate isolated pyloric
      pressure waves (IPPWs) in humans. It is still unresolved, whether these pyloric
      contractions occur within an otherwise quiescent zone of motor and electrical
      activity and whether the presence of the sleeve sensor itself affects this
      nutrient-associated response. In four conscious dogs, comparisons were made
      between paired recordings of myoelectrical and motor activities of the
      antropyloroduodenal region with serosal strain gauge transducers and
      extracellular bipolar electrodes in the presence and absence of an intraluminal
      manometric sleeve-sidehole assembly during intraduodenal infusions of saline and
      a triglyceride emulsion (Intralipid 10%, 0.5 kcal/min). Of 287 isolated pyloric
      pressure waves, detected by the manometric sleeve sensor, 75% were detected as
      isolated pyloric contractions by the strain gauge transducers and 72% occurred in
      the absence of electrical spike activity in the distal antrum or proximal
      duodenum. The lower incidence of isolated pyloric contractions (strain gauges)
      was related to: (1) insensitivity of the pyloric strain gauge transducer in
      comparison to the manometric sleeve sensor (10%), and (2) inability of the
      manometric sleeve-sidehole assembly to detect pressure waves in the distal antrum
      (7%) or proximal duodenum (8%) during antral or duodenal wall motion. The
      presence of the sleeve sensor itself did not affect the number of lipid-induced
      isolated pyloric contractions but increased their amplitude [median 9 (7-15) mN
      vs 4 (2-6) mN; P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131697
TI  - Role of gastric mucosal blood flow in gastroprotective effect of novel xanthine
      derivative.
AB  - The effect of 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119) on
      40% ethanol-induced gastric lesions and gastric mucosal blood flow was
      investigated in rats. Gastric mucosal blood flow was measured by the hydrogen gas
      clearance technique and the test compounds and vehicle were administered
      intraduodenally. A90 6119 dose-dependently increased gastric mucosal blood flow
      and decreased gross and histologic gastric mucosal injury induced by 40% ethanol.
      Both the gastric mucosal blood flow and protective effects of A90 6119 were
      completely attenuated by pretreatment with indomethacin. The findings demonstrate
      that A90 6119 protects against ethanol-induced gastric injury, and this effect
      involves stimulation of endogenous prostaglandin synthesis and an increase in
      gastric mucosal blood flow.

PMID- 8131698
TI  - Nitric oxide in gastroprotection by sucralfate, mild irritant, and nocloprost.
      Role of mucosal blood flow.
AB  - Pretreatment with sucralfate is known to protect gastric mucosa against the
      damaging effect of strong irritants, and this protection is accompanied by an
      increase in mucosal blood flow but the mechanisms underlying these effects have
      not been elucidated. Similar gastroprotective and hyperemic effects can be
      obtained with exogenous prostaglandins (PG), mild irritants such as dilute
      ethanol, and by capsaicin. In this study we investigated the role of nitric oxide
      (NO) in the prevention of ethanol-induced gastric damage and gastric blood flow
      by sucralfate, mild irritant such as 20% ethanol, capsaicin, and nocloprost, a
      stable PGE2 analog. Pretreatment with NG-nitro-L-arginine (L-NNA), an inhibitor
      of NO synthase, enhanced ethanol-induced mucosal damage and reduced dose
      dependently the gastroprotective and hyperemic effects of sucralfate, dilute
      ethanol, and capsaicin. The doses of L-NNA attenuating significantly the
      protective effects of sucralfate or 20% ethanol were 25-50 mg/kg, while those
      reducing the protection by capsaicin were 6.2-12.5 mg/kg. The attenuating effect
      of L-NNA on gastroprotection was reversed by L-arginine but not D-arginine. For
      comparison, the gastroprotective (but not hyperemic) effect of nocloprost was not
      affected by the pretreatment with L-NNA and/or arginine. We conclude that
      sucralfate, mild irritant, and capsaicin activate the NO system that may
      contribute to their gastroprotective effect through enhancing mucosal circulation
      but that NO is not essential for the mucosal protection by PGE2 analog.

PMID- 8131699
TI  - Gastrointestinal irritancy, antiinflammatory activity, and prostanoid inhibition
      in the rat. Differentiation of effects between nabumetone and etodolac.
AB  - Many nonsteroidal antiinflammatory drugs have the ability to cause
      gastrointestinal damage in both animals and man. The aim of the present study was
      to compare nabumetone, a nonacidic drug, with etodolac on rat gastric mucosal
      damage and prostanoid synthesis, while concurrently measuring prostanoid
      production during edema formation in a carrageenan model of paw inflammation. The
      results showed that both drugs inhibited paw exudate prostaglandin E2 and edema
      significantly, but they did not inhibit gastric prostanoid production 4 hr after
      dosing. Gastric damage, however, was observed with etodolac. Additional time
      course studies showed that over a 4-hr period, etodolac, unlike nabumetone,
      markedly inhibited gastric mucosal prostaglandin E2 production, which was
      associated with gastric erosion formation. Further studies demonstrated that
      nabumetone did not induce gastrointestinal damage or blood loss when administered
      to rats in a high antiinflammatory oral dose. In contrast, etodolac produced
      marked gastrointestinal damage and bleeding, which was evident for up to 48 hr
      after the dose. It is suggested that nabumetone's favorable gastrointestinal
      irritancy profile may relate, in part, to its nonacidic nature and to its
      differential effects on prostanoid production.

PMID- 8131700
TI  - Effect of synthetic prostaglandin E2 analog enprostil on omeprazole-induced
      hypergastrinemia and hyperpepsinogenemia.
AB  - This study was undertaken to determine whether the synthetic prostaglandin E2
      analog enprostil is able to inhibit basal and postprandial hypergastrinemia
      induced by omeprazole. We also studied the effect of omeprazole, enprostil, and
      the combination of both drugs on serum pepsinogen A and C levels. Eight normal
      subjects received in random order five-day courses of 40 mg omeprazole once a
      day, 35 micrograms enprostil three times a day, the combination of both drugs,
      and placebo. Omeprazole induced significant increases in basal and postprandial
      serum gastrin and in pepsinogen A and C levels. These increments persisted on the
      day after stopping treatment. Coadministration of enprostil inhibited omeprazole
      induced basal hypergastrinemia and postprandial integrated serum gastrin, but not
      basal serum pepsinogen A and C, while the inhibition on the day after the
      treatment courses only reached statistical significance for the postprandial
      integrated serum gastrin concentration. It is concluded that enprostil inhibits
      omeprazole-induced basal and postprandial hypergastrinemia, with a tendency to
      protracted inhibition after stopping the drugs, and that enprostil does not
      significantly influence omeprazole-induced increases in pepsinogen A and C level.
      Coadministration of enprostil may be helpful in preventing pronounced
      hypergastrinemia in the few patients who show large serum gastrin increases
      during treatment with omeprazole.

PMID- 8131701
TI  - Induction of gastric lesions and hypoglycemic response by food deprivation in
      streptozotocin-diabetic rats.
AB  - Overnight fasting causes hemorrhagic lesions in the stomach of streptozotocin
      (STZ)-induced diabetic rats, but the pathogenetic mechanism remains unknown. The
      present study was performed to investigate the pathogenesis of such lesions
      developed in STZ-diabetic rats after starvation, mainly in relation to blood
      glucose changes. A single injection of STZ (70 mg/kg, intraperitoneally) induced
      hyperglycemic conditions one week after the administration, and high blood
      glucose levels (BGL: > 350 mg%) remained up to three weeks later. The STZ
      diabetic rats developed gastric lesions with the marked reduction of BGL after 18
      hr of fasting, depending upon the duration of diabetes; the lesion score and
      delta BGL reduction in the 3-week-old STZ rats were 32.0 +/- 7.8 mm and > 250
      mg/100 ml, respectively. Acid secretion in the pylorus-ligated rats was not
      significantly changed in the STZ-induced diabetic conditions for the initial two
      weeks but slightly decreased at three weeks when compared with normal rats.
      Fasting of normal rats for 18 hr did not cause either BGL reduction or any lesion
      in the stomach. In the 3-week-old STZ animals, the severity of gastric lesions
      increased with the duration of fasting (4-18 hr) and was again closely associated
      with the degree of delta BGL reduction. These lesions induced by 18 hr of
      starvation in 3-week-old STZ rats were significantly inhibited by pretreatment
      with insulin (4 units/rat/day) for the last one week to maintain BGL within
      normal ranges or by intravenous infusion of 25% glucose during fasting period.
      Both of these treatments significantly prevented BGL reduction in response to
      fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131702
TI  - Estrogens, androgens, and EGF receptor expression in gastric carcinoma induced by
      N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - Complex and conflicting relationships between epidermal growth factor (EGF),
      estrogens (E), androgens (A), and related receptors (EGF-R, E-R, A-R) have been
      reported in different biological situations associated with cell proliferation.
      There is also evidence that EGF and sex hormone receptors may be involved in
      normal and neoplastic growth of the gastrointestinal mucosa. In this study, we
      investigated the behavior of EGF receptors and sex hormone and related receptors,
      during N-methyl-N'-nitro-N-nitrosoguanidine (NG)-induced gastric carcinogenesis
      in Sprague-Dawley male rats. Four groups of 15 rats each (10 NG-treated and five
      controls) were sacrificed after 1, 20, 30, and 40 weeks of treatment. Gastric
      tissue from each rat was processed for receptor status (number and affinity) and
      proliferative activity. A significant and progressive decrease of A-R and EGF-R
      was observed starting from the 20th week, while no change of E-R occurred
      throughout the experiment. Cell proliferation in the gastric mucosa of NG-treated
      rats increased after 30 weeks of treatment. These data indicate that NG treatment
      is able to modify the receptor status of gastric mucosa in rats.

PMID- 8131703
TI  - Effect of experimental cold pain stress on gastroesophageal junction.
AB  - The impact of stress on gastroesophageal reflux and antireflux mechanisms remains
      largely unexplored. To a major extent, reflux depends on a balance between
      gastroesophageal junction resistance to flow and gastric tone. We hypothesized
      that these two forces could be differently affected by stress, and to test the
      hypothesis we quantified in 10 healthy volunteers the effect of an acute
      stressful stimulus (cold pain) upon both gastroesophageal junction resistance
      (measured by a pneumatic resistometer) and gastric tone (measured by an
      electronic barostat). Such measurements were performed both under basal
      conditions and during stress stimulation (hand immersion in cold water for 5
      min), on two separate days. The cardiovascular autonomic response was
      simultaneously monitored as changes in blood pressure and pulse rate. We found
      that, taken as a whole, cold stress significantly decreased gastroesophageal
      resistance (flow increase from 347 +/- 29 ml/min to 526 +/- 58 ml/min) as well as
      gastric tone (volume increase from 147 +/- 10 ml to 218 +/- 17 ml) (P < 0.02 for
      both). However, responses showed marked intra- and interindividual variation.
      Moreover, we found no relationship between changes in resistance to flow at the
      junction and either the cardiovascular autonomic response or the discomfort
      produced by cold stress. Changes in gastric tone were similarly unrelated to
      autonomic and perceptive responses. We conclude that in man experimental stress
      induced by cold pain tends to disrupt each of two opposite mechanisms that
      control gastroesophageal reflux: gastroesophageal resistance to flow and gastric
      tone. However, since both are decreased by stress, gastroesophageal function is
      largely maintained.

PMID- 8131704
TI  - Macroscopic healing of esophagitis does not improve esophageal motility.
AB  - The purpose of the present study was to prospectively determine if healing of
      esophagitis as assessed by endoscopy results in improved esophageal motility.
      Thirty-one patients with erosive esophagitis who were randomized to receive
      either omeprazole 20 mg once daily or placebo completed the double-blind study.
      All patients underwent endoscopy and esophageal motility before treatment and at
      four weeks after treatment. Twenty-two healthy volunteers underwent esophageal
      manometry and served as normal controls. Manometric tracings were coded,
      randomized, and analyzed blindly. Compared to normal controls, patients with
      esophagitis had significantly lower LESP, decreased amplitude of peristaltic
      contractions, and increased occurrence of abnormal contractions. Omeprazole was
      superior to placebo in healing of esophagitis. However, healing of esophagitis
      was not associated with any improvement in esophageal motility. The manometric
      data suggest that the motility disturbance seen in esophagitis is not secondary
      to the esophagitis but rather a primary phenomenon. The lack of improvement of
      esophageal motility with healing may explain the high recurrence of esophagitis
      in clinical trials following discontinuation of omeprazole.

PMID- 8131705
TI  - Morphology and pathology of radiation-induced esophagitis. Double-blind study of
      naproxen vs placebo for prevention of radiation injury.
AB  - Radiation-induced esophagitis can cause substantial morbidity. Experiments in lab
      animals have shown that pretreatment with indomethacin protects the esophagus
      from radiation damage. We conducted a prospective, double-blind, randomized trial
      of naproxen vs placebo in patients undergoing thoracic radiation therapy for lung
      cancer. Twenty-eight patients were enrolled, of which 26 completed the study.
      Sixteen patients were given a short course of radiation (30 Gy/10 fractions/2
      weeks), and 10 patients were given a longer course and a larger dose (40-50 Gy/25
      fractions/5 weeks). Half of the irradiated patients were treated with naproxen,
      375 mg, taken orally twice a day, and half were given an identical placebo. All
      patients were given ranitidine 300 mg, taken orally once a day. Study drugs were
      taken throughout the course of radiation. Endoscopy with esophageal biopsies and
      brushings was performed before and on the last day of treatment. Patients kept a
      daily diary for symptom scoring. Symptoms such as chest pain, dysphagia,
      odynophagia, and/or heartburn were reported in 15 patients from both subgroups,
      resulting in diet restriction to liquids only in eight patients and requiring
      temporary discontinuation of radiation therapy in one of them. Approximately half
      the patients in each subgroup developed esophagitis, usually mild and usually
      limited to the proximal esophagus. Severity of symptoms was not proportional to
      the severity of esophagitis. Candidiasis was documented in eight patients, but
      only four had symptoms that were severe in one. We conclude that acute radiation
      injury to the esophagus is observed in approximately half the patients receiving
      radiation therapy and can result in substantial morbidity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8131706
TI  - Could immunostimulant drugs be useful in apparently medically refractory Crohn's
      disease?

PMID- 8131707
TI  - Percutaneous transhepatic microwave coagulation therapy for hepatocellular
      carcinoma proliferating in the bile duct.

PMID- 8131708
TI  - Cholangiocarcinoma and Crohn's disease.
AB  - Cholangiocarcinoma is an infrequent complication of inflammatory bowel disease.
      Although increasing numbers of cholangiocarcinomas are being reported in
      association with ulcerative colitis, the occurrence of this disease in patients
      with Crohn's disease is rare. To understand this complication better, we have
      reported the case of a patient with Crohn's disease in whom cholangiocarcinoma
      subsequently developed and reviewed the literature.

PMID- 8131709
TI  - Pre-irradiation haematological effects of the bacterial extract Broncho-Vaxom and
      postirradiation acceleration recovery from radiation-induced haematopoietic
      depression.
AB  - Effects of the bacterial extract Broncho-Vaxom (BV), free of endotoxin, on
      haematopoietic parameters of peripheral blood, bone marrow, spleen and thymus
      were investigated in normal and irradiation-myelosuppressed C57BL/6 mice. BV in
      normal (nonirradiated) mice induced transient lymphocytopenia and increased
      granulocytes, particularly neutrophils, six to nine hours after administration.
      Elevated numbers of peripheral blood macroreticulocytes were observed during the
      third hour. In the splenic red pulp, enhancing haemopoietic activity, foci of
      fibroblasts began to appear more frequently from the first hour to 24 h. In
      lymphatic follicles of the spleen and thymus, the incidence of macrophages or
      monocytes began to increase three hours after BV application. Twenty-four hours
      later thymus weight decreased by 27%. In the bone marrow, enhanced proliferation
      of eosinophils was observed from hour nine, with maximum proliferation at hour
      24. BV treatment 24 h before irradiation had a notable radio-protective effect,
      manifested by accelerated haemopoietic recovery during the postirradiation
      period. Accelerated myelopoiesis, erythropoiesis and megakaryocytopoiesis
      resulted in accelerated peripheral blood recovery. However, BV had no effect on
      thymus reparation as suggested by similar effects in BV protected and BV
      nonprotected animals during the entire period which followed a 6.5 Gy dose.

PMID- 8131710
TI  - Antiviral activity of nerve growth factor in vitro.
AB  - The antiviral activity of 'nerve growth factor' (NGF) on non-oncogenic DNA, on
      RNA viruses and on Moloney sarcoma retrovirus was evaluated in vitro. NGF was
      active against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2
      (HSV-2) and Moloney sarcoma virus (MSV) at non toxic concentrations. The effects
      of different treatment regimens on HSV-1 infections indicate that the inhibitory
      action of NGF occurs at the early stages of viral replication. No activity was
      noted against coxsackie virus B1 (Cox B1), respiratory syncytial virus (RSV),
      Semliki forest virus (SFV), encephalomyocarditis (Columbia SK) and adenovirus of
      infectious canine hepatitis (ICH) at the highest concentrations tested.

PMID- 8131711
TI  - A new antioxidant drug limits brain damage induced by transient cerebral
      ischaemia.
AB  - Restoration of blood flow after an ischaemic event generates the formation of
      oxygen radicals which could augment brain damage. The authors studied the effects
      of different doses (50, 100, 200 mg/kg/i.p.) of a new antioxidant, IRFI-016,
      [2(2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzofuranyl) acetic acid] on brain
      damage in the Mongolian gerbil induced by 5 min of bilateral carotid occlusion
      (BCO) followed by reperfusion. Post-ischaemic brain malondialdehyde (MDA) levels
      and locomotor activity at different times and delayed neuronal death of
      hippocampal CA1 area on the fourth day after occlusion were evaluated. During
      reperfusion, after BCO, enhancement of brain MDA occurs (37.5%, 62.5% and 100% at
      15, 30 and 60 min of reperfusion, respectively). Brain MDA postischaemic
      increases were reduced at 15 min of reperfusion to 15.4% and 44.4% by IRFI-016,
      100 and 200 mg/kg, respectively. After 30 min of reperfusion brain MDA was
      reduced to 31.25% and 53.13% by IRFI-016 100 and 200 mg/kg, respectively.
      Hyperactivity and delayed neuronal death of CA1 were significantly reduced in
      postischaemic gerbils treated with the highest doses of IRFI-016. Results
      indicate that pretreatment with the antioxidant IRFI-016 improves in a dose
      dependent manner brain damage induced by ischaemia and reperfusion in the gerbil.

PMID- 8131712
TI  - Comparative study on the effects of chlorite oxygen reaction product TCDO
      (tetrachlorodecaoxygen) and sodium chlorite solution (NaClO2) with equimolar
      chlorite content on bone marrow and peripheral blood of BDIX rats.
AB  - The effects of the chlorite-oxygen reaction product TCDO (tetrachlorodecaoxygen,
      active ingredient of the systemic application form of WF 10) were investigated on
      bone marrow and peripheral blood of BDIX rats in comparison to a sodium chlorite
      solution with a chlorite content identical to that of WF 10. Despite difficulties
      in determining the chemical differences between TCDO and a sodium chlorite
      solution, their differing effects on cells, tissue and organism were striking.
      The following characteristics have been observed: Stimulation of the bone marrow,
      evidenced by the pronounced increase in mature granulocytes, pronormo- and
      normoblasts, or increased cell proliferation rate, determined by means of the
      BrdUrd method, was achieved only with WF 10 (TCDO). Stimulation of the bone
      marrow led in turn to increased numbers of leucocytes and monocytes in the
      peripheral blood. In addition, WF 10 induced the production of large granular
      lymphocytes (LGLs), referred to as natural killer cells (NK-cells). In contrast,
      NaClO2 solution suppressed bone marrow function, exhibiting a toxic effect when
      given on a long-term basis. At the same time the number of mature granulocytes as
      well as pronormo- and normoblasts decreased, while the presence of LGLs was not
      observed. The results showed that TCDO is a potent stimulator of the bone marrow
      function and an effective modulator of the entire immune system. The toxic effect
      of chlorite, derived from the TCDO matrix, is not noticeable, being completely
      compensated by the favourable effects of TCDO.

PMID- 8131713
TI  - Delaying effects of dietary eicosapentaenoic-docosahexaenoic acids on development
      of "fatty streaks" in hypercholesterolaemic rabbits. A morphological study by
      scanning electron microscopy.
AB  - Besides causing functional and clinical damage, hypercholesterolaemia also causes
      morphological alterations of vascular endothelium. Rabbits fed a diet with 1%
      cholesterol for 4, 6, or 8 weeks are experimental models for
      hypercholesterolaemia, with pathological structural changes in vascular luminal
      surface. Morphological investigation by scanning electron microscopy was
      performed to reveal the tridimensional growth of these lesions and the
      differences in this growth induced by concomitant dietary assimilation of fish
      oil (2 g/day). Macroscopic reduction in fatty-streak production was clearly seen
      in rabbits fed fish-oil. Scanning electron microscopy confirmed that the area of
      intimal lesions was only 21 +/- 6% in this group, while in the group fed
      cholesterol without fish oil, the lesioned area attained 76 +/- 5%. Endothelial
      swelling was less marked, probably due to reduced intracellular lipid
      accumulation into the foam cells. Adherent macrophages were also fewer. The
      differences might be correlated with protection against the lipoproteins'
      atherogenic effects and to hemorheological benefits produced by the Omega-3 fatty
      acid (85%) present in fish-oil.

PMID- 8131714
TI  - Effects of warfarin on thrombosis of the jugular veins of rabbits induced by
      prolonged stasis.
AB  - We have studied the effects of warfarin pretreatment on blood coagulation tests,
      thrombosis and endothelial damage in the rabbit after 2 h of subsequent venous
      stasis. We found that 3 mg/kg warfarin significantly modified the results of
      prothrombin time, activated partial thromboplastin time and ProComplex tests. The
      incidence of thrombosis was not reduced by warfarin, but the weight of the
      thrombi were inversely related to the effects of the drug on blood coagulation.
      The endothelial cells showed some degree of damage. In conclusion, warfarin
      neither prevents endothelial damage nor reduces the incidence of thrombosis after
      venous stasis, but retards the growth of thrombi.

PMID- 8131715
TI  - [Somatostatin receptor scintigraphy in the primary diagnosis and follow-up care
      of gastrinoma].
AB  - Somatostatin receptor scintigraphy (SRS) was performed in 14 patients (five men,
      nine women; mean age 51.5 [20-71] years) with Zollinger-Ellison syndrome (ZES), a
      gastrinoma proven in 7 and suspected on clinical or biochemical grounds in 7. The
      results were compared with those obtained by other methods (ultrasound, computed
      tomography, angiography). All 12 known tumour manifestations were demonstrated by
      SRS in seven patients with histologically confirmed gastrinoma. In four patients
      previously non-localized tumour was revealed by SRS, while in seven other
      patients the procedure led to modification of the treatment (primary tumour
      resection: n = 3, resection of metastases: n = 2, percutaneous radiation or
      chemoembolization: one each). These results suggest the following indications for
      SRS: (1) staging or re-staging in histologically proven gastrinoma and (2) search
      for primary tumour in clinically and biochemically suspected ZES.

PMID- 8131716
TI  - [Acute intravasal hemolysis in Clostridium perfringens sepsis. Differential
      diagnosis of hemolytic episodes].
AB  - A 19-year-old man with acute lymphoblastic leukaemia developed fever, general
      deterioration and somnolence 3 days after a cycle of cytostatic treatment. He had
      anaemia (haemoglobin 6.6 g/dl), leukopenia (100/microliters) and thrombocytopenia
      (7,000/microliters). As an acute septicaemia was suspected he received broad
      spectrum antibiotic therapy, together with two units of red cell and platelet
      concentrates. However, his condition worsened rapidly over the next 5 hours
      (meningism, seizures, fever to 41.1 degrees C, dyspnoea). Another blood count
      revealed severe haemolysis. Computed tomography of the skull demonstrated
      multilocular intraparenchymal gas formation. Although the antibiotic treatment
      was extended the patient died several hours later. Retrospective examination for
      suspected transfusion mismatch provided no evidence for erythrocyte
      incompatibility. But there was liberation of T-antigen as sign of a bacterial
      cause of erythrocyte damage. An anaerobic blood culture grew Clostridium
      perfringens. This case demonstrates that acute intravascular haemolysis in
      septicaemia should be considered in the differential diagnosis of transfusion
      mismatch.

PMID- 8131717
TI  - [Reopening of completely closed aortocoronary venous bypasses using angioplasty
      and 24-hour local fibrinolysis].
AB  - Recent occlusion of aortocoronary venous bypass grafts had occurred in three
      patients, aged between 64 and 67 years. In all three recanalization was achieved
      after 8 hours, two and five days, respectively, of coronary angioplasty combined
      with local urokinase infusion for 24 hours. The procedure consisted of passing a
      guide-wire through the occluded bypass graft, the tip of the wire then being
      advanced to the periphery of the native coronary artery. The balloon was then
      repeatedly dilated along the length of the graft. Primary opening was not
      achieved in one of the grafts, and the other two closed again, despite repeated
      and prolonged balloon dilatation. In all three patients a coronary infusion
      catheter was then placed into the graft lumen and urokinase (3 mill. units)
      infused over 24 hours. An angiogram 24 hours later demonstrated an open bypass
      graft (residual stenosis < 50%). Angiography 9 to 14 weeks later revealed
      restenosis in one case, but it was reopened by balloon dilatation and stent
      insertion, while the other two had remained open without significant stenosis.

PMID- 8131718
TI  - [Adjuvant therapy of breast carcinoma].

PMID- 8131719
TI  - [Diagnosis and significance of antinuclear antibodies].

PMID- 8131720
TI  - [Inquiry regarding the suspension of a doctor's assistant after pregnancy.
      Decision of the Federal Labor Court of July 1, 1993].

PMID- 8131721
TI  - [Universal donor blood].

PMID- 8131722
TI  - [Relapse after goiter resection].

PMID- 8131723
TI  - [Minimal heparinization].

PMID- 8131724
TI  - [The control of Aujeszky's disease using surface vaccination. 2. Serologic
      studies of the occurrence of latent infection by Aujeszky's disease virus in
      fattening swine].
AB  - The aim of the study was to prove in a region in the North-West of Germany that
      there is the possibility to decrease the prevalence of latent Aujeszky's Disease
      infections by means of a systematic vaccination. For this, the most important
      precondition of the success in a high population immunity that is maintained also
      in the finishing pig until slaughter. Since it is known that maternal antibodies
      interfere with the active immunization in the prefattening period, procedures
      were to be found that guarantee a high immunity in spite of the colostral
      antibodies. The results of the study show that the existing recommendation for
      vaccinating fattening pigs are sufficient for the prevalence of latent
      infections. They also confirm the necessity to carry out a check- and slaughter
      policy at the end of the eradication program.

PMID- 8131725
TI  - [Experiences with the use of xylazine for sacral epidural anesthesia in cattle].
AB  - The effect of epidural administered xylazine was investigated in 10 mature
      Holstein cows (mean age: 5.4 +/- 1.2 years, mean BW: 572 +/- 23 kg): 5 cows were
      treated with xylazine in a low dose of 0.05 mg/kg body weight, 3 cows in a medium
      dose (0.07 mg/kg BW) and 2 cows in a high dose (0.1 mg/kg BW). Xylazine dosages
      were diluted in sterile saline to a final volume of 5 ml. As a control, lidocaine
      (5 ml of a 2% solution) was given to 5 cows epidurally. Duration of regional
      anaesthesia after low dose of xylazine (0.05 mg/kg BW) was significant longer
      (mean: 2.2 hours) compared to lidocaine treated cows (mean: 1.1 hour). Regional
      extension of anaesthesia was comparable after dosing with xylazine and lidocaine
      (tail, after, vulva and perineum). All cows remained standing, but in xylazine
      treated cows systemic effects, e.g. mild sedation, decreased heart- and
      respiratory rates, decreased rumen motility and mild bloat were observed. With
      increased dosages of xylazine a prolongation of epidural anaesthesia up to 3
      hours was achieved, but regional extension of this effect remained nearly
      unchanged. With increased xylazine dosages, cows showed marked sedation and
      ataxia and sternal recumbency were induced.

PMID- 8131726
TI  - [Effects of orally administered therapeutic drugs on the fermentation processes
      in the rumen fluid of ruminating cattle (in vitro). 6. Copper sulfate].
AB  - In 50 trials, incubating rumen fluid at 39 degrees C for 6 hours with starch and
      urea as nutrients, the effects of simulated oral administration of 3 g copper
      sulphate per animal and day (50 mg copper sulphate per liter rumen fluid) on
      rumen fermentation patterns have been examined. In two series of five incubations
      each in rumen fluid of five donors (total = 50), doses of 2.25 g (37.5 mg/l) and
      4.5 g (75 mg/l) copper sulphate were simulated. The five donors (517-720 kg) of
      ruminal fluid were fed a ration of hay and concentrate twice daily and water was
      offered ad libitum. Rumen fluid was sampled 2.5 hours after feeding in the
      morning and immediately incubated in the artificial rumen. While at 2.25 g an
      effect was hardly seen and 4.5 g were followed by great changes, 3 g appeared to
      be the limiting dose that reduced the amylolysis (-23.9%; p < 0.001), the
      production of volatile fatty acids (-23.5%; p < 0.001) and methane (-23.6%; p <
      0.001), but caused a higher concentration of ammonia (+11.2%; p < 0.001).
      Therefore 2 g CuSO4/animal/day is recommended as maximum dose in cattle to
      overcome Cu-deficiency.

PMID- 8131727
TI  - [The genital microflora in the stallion--microbiological study of presecretion
      samples from 1972 to 1991].
AB  - From 1972 to 1991, presecretion on an average of 183 stallions per year had been
      examined. Facultatively pathogenic germs were ascertained in 13.5% of the
      samples. However, the portion showed considerable annual fluctuation, as did the
      percentage of the different kinds of germs. In most of the cases, only minimal
      growth had been observed in culture. Except for the total percentage, these
      results are contradictory to those we found during the examination of cervical
      swabs of mares. In order to ascertain the importance of the respective results
      and to render possible a correct interpretation, the constancy of the
      facultatively pathogenic germs was investigated additionally. It was distinctly
      dependent on the quantity and--to a lesser extent--on the kind of the germs as
      well. According to the present results, minimal growth in culture throughout only
      indicates a temporary colonization of the genitals. These results--except for the
      indication of CEMO--may be neglected, unless otherwise indicated by clinical
      findings or by anamnesis.

PMID- 8131728
TI  - [Field infection with BVD virus in swine: epidemiology and diagnosis].
AB  - In a pig breeding herd in Lower Saxony infertility of breeding sows had been
      repeatedly observed. Growth retardation and post mortem findings in two piglets
      gave clinical indication to swine fever/hog cholera. A virus was isolated and
      typed by monoclonal antibodies as pestivirus not identical with hog cholera virus
      (HCV). In neutralization tests applying the field isolate, HCV and bovine viral
      diarrhea (BVD) virus the sera breeding sows and weaner pigs yielded high
      neutralizing antibody titres against the pestivirus field isolate but low titres
      against HCV. Specific antibodies against HCV were ruled out by a complex trapping
      blocking (CTB) ELISA. Intranasal inoculation of a weaner pig with spleen
      homogenate led to a short-termed viraemia without clinical signs but
      seroconversion with high antibody titres against the homologous pestivirus. In an
      in-contact pig no virus was detected and no antibody demonstrated within a period
      of 18 weeks.

PMID- 8131729
TI  - [Detection of toxin-producing strains of Pasteurella multocida in nasal and
      tonsil swabs, a possibility for the control of atrophic rhinitis in swine
      breeding herds? Parallel comparison with other research methods].
AB  - Nasal, and partly tonsil swabs from pigs have been investigated by cell culture
      and ELISA respectively on toxigenic Pasteurella multocida strains. The controlled
      animals are from 89 non atrophic rhinitis- and 42 a.r.-positive herds. Toxin
      forming strains could not be isolated in non suspicious herds. 23 out of 42
      infected herds showed toxigenic Pasteurellae. Despite a high increase in sample
      numbers, Pasteurella could not be detected in 19 infected herds (45%). When
      diagnosing atrophic rhinitis, we thus recommend to rely only on positive results
      of isolation. In all other cases, all other methods will have to be used in
      combination. Further research is necessary to find safe and fast test methods.
      According to recent experience, the blood-serological toxin screening test can be
      considered useful.

PMID- 8131730
TI  - [Observations of the liver copper content in sheep in northwest Germany].
AB  - Samples of liver tissue from sheep (n = 231), which were send to the Institute on
      Animal Nutrition, School of Veterinary Sciences Hannover, were analyzed for
      copper; the results were evaluated in reference to animal's age and race. In
      tissue of young sheep (up to 4 weeks) the copper concentration was about 250 (56
      770) mg/kg dry matter (DM); values < 120 as well as > 300 mg/kg DM were observed
      in few cases only. From 198 data of adult sheep 28% suggested a copper deficiency
      (< 50 mg/kg DM), while 21% were the result (> 500 mg/kg DM) of a critically
      elevated copper intake. Sheep of the typical heath race presented the main part
      of those affected by copper deficiency; the races merino and Texel dominated in
      the group with elevated copper concentrations in liver tissue.

PMID- 8131731
TI  - [Prevalence of antibodies against the viruses of European swine fever, Aujeszky's
      disease and "porcine reproductive and respiratory syndrome" in wild boars in the
      federal states Sachsen-Anhalt and Brandenburg].
AB  - During the hunting season from 1991/1992 blood samples were collected from wild
      boar shot in the Federal States of Sachsen-Anhalt (482 samples) and Brandenburg
      (177 samples) which corresponds to 2.1 and 0.4% of the total hunting bag. All
      sera were screened in a complex trapping blocking (CTB) ELISA for antibodies
      against hog cholera virus (HCV) and in an indirect ELISA for antibodies against
      Aujeszky's disease virus (ADV). Additionally the sera were tested for
      neutralizing antibodies against HCV strain ALFORT/187, bovine viral diarrhoea
      virus (BVDV) strains NADL and 1138/69, and against an ADV field isolate. In case
      of questionable results sera were tested against HCV strain "BERGEN", HCV vaccine
      strain "RIEMS" and three HCV field isolates from wild boar. The serological
      testing for antibodies against "porcine reproductive and respiratory syndrome
      virus" (PRRSV) was carried out in indirect immunoperoxidase monolayer assay
      (IPMA). Four sera (Sachsen-Anhalt) reacted positive in CTB-ELISA. Seven sera
      yielded neutralizing antibodies against HCV but only one of the "non-negative"
      samples scored positive in both techniques, ELISA and VNT. Two sera (Brandenburg)
      had low neutralizing antibody titres against Alfort/197 but scored negative in
      CTB-ELISA. Screening for antibodies against ADV of 640 sera led to 13 positive
      sera including 5 positive findings in both ELISA and VNT. Antibodies against
      PRRSV were detected in two sera which were collected Sachsen-Anhalt. Estimations
      resulted in a prevalence of about 5% for antibodies against HCV.

PMID- 8131732
TI  - [Science and society: a confidence crisis?].
AB  - Modern technical world is essentially dependent on science and technology. Due to
      this, more and more potential dangers between science and society build up,
      leading to a general fear of the threatening progress of science on all sectors,
      especially in nuclear research and gene technology, thus arousing the question of
      a crisis of confidence between science and society. It will be proved that this
      crisis does not exist. The thing to be done is to make science much more
      transparent than before. "Belief in science and fear of science" are discussed in
      detail, including the fear of a risk (reckless society). Further paragraphs deal
      with "limitations of situations of misery" by way of science and the "limits of
      science and action". The discussion of this matter entails a short comment on the
      "responsibility of the scientist". The political function of the scientist is
      underlined in a kind of "outlock". It is concluded that we cannot cope with a
      crisis of confidence between science and society. The scientification and
      technification of the biosphere cannot be reversed. Mankind must and will somehow
      manage the future.

PMID- 8131733
TI  - [Non-recognition of a second fetus in a recumbent cow during veterinary
      obstetrical assistance (expert opinion)].
AB  - The objective of the expert opinion presented in this paper is the missing of a
      second fetus after veterinary obstetrical assistance in a downer cow. The
      necessity of a thorough examination after obstetrical manipulation is stressed
      with special reference to problems occurring in recumbent cows. In addition,
      possible complications after inappropriate removal of retained placental fetal
      membranes are discussed.

PMID- 8131734
TI  - Crystal structure of vitelline membrane outer layer protein I (VMO-I): a folding
      motif with homologous Greek key structures related by an internal three-fold
      symmetry.
AB  - The crystal structure of vitelline membrane outer layer protein I (VMO-I), which
      is isolated from the vitelline membrane outer layer of hen's eggs, has been
      determined by the multiple isomorphous replacement method and refined to an R
      factor of 18.8% at 2.2 A resolution. The main chain folds into an unusual
      structure that consists of three beta-sheets forming Greek key motifs, which are
      related by an internal pseudo three-fold symmetry. The internal portion
      surrounded by these three beta-sheets is filled with hydrophobic side chains.
      This conformational feature coincides with three internal repeats in the
      sequence. Although a similar fold exists in the second domain of delta-endotoxin,
      there are significant structural differences between the two proteins, with the
      three-fold symmetry being most regular in VMO-I.

PMID- 8131735
TI  - Three-dimensional structure of the rotavirus haemagglutinin VP4 by cryo-electron
      microscopy and difference map analysis.
AB  - The three-dimensional structure of the rotavirus spike haemagglutinin viral
      protein 4 (VP4) has been determined to a resolution of 26 A by cryo-electron
      microscopy and difference analysis of intact virions and smooth (spikeless)
      particles. Native and spikeless virions were mixed prior to cryo-preservation so
      that both structures could be determined from the same micrograph, thereby
      minimizing systematic errors. This mixing strategy was crucial for difference map
      analysis since VP4 only accounts for approximately 1% of the virion mass. The VP4
      spike is multi-domained and has a radial length of approximately 200 A with
      approximately 110 A projecting from the surface of the virus. Interactions
      between VP4 and cell surface receptors are facilitated by the bi-lobed head,
      which allows multi-site interactions, as well as the uniform distribution of the
      VP4 heads at maximum radius. The bi-lobed head is attached to a square-shaped
      body formed by two rods that have a slight left-handed helical twist. These rods
      merge with an angled, rod-like domain connected to a globular base approximately
      85 A in diameter. The anchoring base displays pseudo 6-fold symmetry. This
      surprising finding may represent a novel folding motif in which a single
      polypeptide of VP4 contributes similar but non-equivalent domains to form the
      arms of the hexameric base. The VP4 spike penetrates the virion surface
      approximately 90 A and interacts with both outer (VP7) and inner (VP6) capsid
      proteins. The extensive VP4-VP7 and VP4-VP6 interactions imply a scaffolding
      function in which VP4 may participate in maintaining precise geometric register
      between the inner and outer capsids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131736
TI  - The assembly of cytochrome b6/f complexes: an approach using genetic
      transformation of the green alga Chlamydomonas reinhardtii.
AB  - As an approach to the study of the biogenesis of the cytochrome b6/f complex, we
      characterized the behaviour of its constitutive subunits in mutant strains of
      Chlamydomonas reinhardtii bearing well-defined mutations. To this end, we have
      constructed three deletion mutant strains, each lacking one of the major
      chloroplast pet genes: the delta petA, delta petB and delta petD strains were
      unable to synthesize cyt f, cyt b6 and subunit IV (suIV) respectively. Western
      blotting analysis, pulse-labelling and pulse-chase experiments allowed us to
      compare the cellular accumulation, the rates of synthesis and the turnover of the
      cyt b6/f subunits remaining in the various strains. We show that the rates of
      synthesis of cyt b6 and suIV are independent of the presence of the other
      subunits of the complex but that their stabilization in the thylakoid membranes
      is a concerted process, with a marked dependence of suIV stability on the
      presence of cyt b6. In contrast, mature cyt f was stable in the absence of either
      suIV or cyt b6 but its rate of synthesis was severely decreased in these
      conditions. We conclude that the stoichiometric accumulation of the chloroplast
      encoded subunits of the cyt b6/f complex results from two regulation processes: a
      post-translational regulation leading to the proteolytic disposal of unassembled
      cyt b6 and suIV and a co-translational (or early post-translational) regulation
      which ensures the production of cyt f next to its site of assembly.

PMID- 8131737
TI  - Electron transfer from plastocyanin to photosystem I.
AB  - Mutant plastocyanins with Leu at position 10, 90 or 83 (Gly, Ala and Tyr
      respectively in wildtype) were constructed by site-specific mutagenesis of the
      spinach gene, and expressed in transgenic potato plants under the control of the
      authentic plastocyanin promoter, as well as in Escherichia coli as truncated
      precursor intermediates carrying the C-terminal 22 amino acid residues of the
      transit peptide, i.e. the thylakoid-targeting domain that acts as a bacterial
      export signal. The identity of the purified plastocyanins was verified by matrix
      assisted laser desorption/ionization mass spectrometry. The formation of a
      complex between authentic or mutant spinach plastocyanin and isolated photosystem
      I and the electron transfer has been studied from the biphasic reduction kinetics
      of P700+ after excitation with laser flashes. The formation of the complex was
      abolished by the bulky hydrophobic group of Leu at the respective position of G10
      or A90 which are part of the conserved flat hydrophobic surface around the copper
      ligand H87. The rate of electron transfer decreased by both mutations to < 20% of
      that found with wildtype plastocyanin. We conclude that the conserved flat
      surface of plastocyanin represents one of two crucial structural elements for
      both the docking at photosystem I and the efficient electron transfer via H87 to
      P700+. The Y83L mutant exhibited faster electron transfer to P700+ than did
      authentic plastocyanin. This proves that Y83 is not involved in electron transfer
      to P700 and suggests that electron transfer from cytochrome f and to P700 follows
      different routes in the plastocyanin molecule. Plastocyanin (Y83L) expressed in
      either E. coli or potato exhibited different isoelectric points and binding
      constants to photosystem I indicative of differences in the folding of the
      protein. The structure of the binding site at photosystem I and the mechanism of
      electron transfer are discussed.

PMID- 8131738
TI  - A small polypeptide triggers complete degradation of light-harvesting
      phycobiliproteins in nutrient-deprived cyanobacteria.
AB  - Phycobilisomes are the multiprotein complexes predominantly responsible for
      harvesting light energy in cyanobacteria and some eukaryotic algae. When the
      cyanobacterium Synechococcus sp. strain PCC 7942 is deprived of an essential
      nutrient, the phycobilisomes are specifically and rapidly degraded. Degradation
      may be either partial (after phosphorus deprivation) or complete (after sulfur or
      nitrogen deprivation). We have developed a visual screen to obtain mutants unable
      to degrade their phycobilisomes upon nutrient starvation. Complementation of one
      of these mutants led to the identification of a gene, designated nblA, that
      encodes a 59 amino acid polypeptide essential for phycobilisome degradation.
      Transcription of nblA increases dramatically in sulfur- or nitrogen-deprived
      cells and moderately in phosphorus-deprived cells. Using the phosphorus-regulated
      alkaline phosphatase (phoA) promoter as a tool, we engineered constructs from
      which we could control the expression of either sense or antisense nblA.
      Increased expression of sense nbLA caused complete phycobilisome degradation
      during phosphorus deprivation, while expression of antisense nblA prevented
      phycobilisome degradation. Hence, nblA is necessary, and may be sufficient, for
      the degradation of phycobilisomes under adverse environmental conditions. Further
      investigation of the mechanism by which nblA causes phycobilisome destruction may
      reveal general principles that govern the specificity of macromolecular complex
      degradation.

PMID- 8131739
TI  - A dramatic shift in the transmembrane topology of a viral envelope glycoprotein
      accompanies hepatitis B viral morphogenesis.
AB  - The envelope of hepatitis B virus contains three related glycoproteins (termed L,
      M and S) produced by alternative translation initiation in a single coding
      region. The smallest of these, the S protein, is a 24 kDa glycoprotein with
      multiple transmembrane domains. The M and L proteins contain the entire S domain
      at their C-termini, but harbor at their N-terminal additional (preS) domains of
      55 or 174 amino acids, respectively. Most of these preS residues are displayed on
      the surface of mature virions and hence would be expected to be translocated into
      the endoplasmic reticulum (ER) lumen during biosynthesis. Using a coupled, in
      vitro translation/translocation system we now demonstrate that, contrary to
      expectation, virtually all preS residues of the L protein are cytoplasmically
      disposed in the initial translocation product. This includes some preS sequences
      which in the M protein are indeed translocated into the ER lumen. Since preS
      sequences are found on the external surface of the virion envelope, our results
      indicate that during or following budding a dramatic reorganization of either the
      envelope proteins or the lipid bilayer (or both components) must occur to allow
      surface display of these sequences. These findings imply that some membrane
      budding events can have remarkable and previously unsuspected topological
      consequences.

PMID- 8131740
TI  - Membrane protein lateral interactions control Semliki Forest virus budding.
AB  - Semliki Forest virus, SFV, directs the synthesis of two membrane proteins, p62
      and E1, which form a p62E1 heterodimer in the endoplasmic reticulum. After being
      transported to the plasma membrane (PM), they are incorporated into the virus
      membrane during the process of virus budding. Electronmicroscopic analyses of the
      envelope in matured virus show that the heterodimers are clustered into trimeric
      structures (spikes) which further form a regular surface lattice with T = 4. In
      this work we have used a genetic approach to study the importance of the
      trimerization event for virus budding. We have coexpressed a budding competent
      form of the virus heterodimer with another one which cannot be used for particle
      formation because of a defect in nucleocapsid (NC) binding. We show that the NC
      binding-deficient heterodimer is able to inhibit the budding of the competent one
      in a concentration-dependent manner and that the NC binding-competent
      heterodimers can rescue the incompetent ones into virus particles. This suggests
      that the heterodimers are complexed together, probably into the trimeric
      structures (spikes), at the PM to expose a multivalent binding site for the NC
      and thereby drive efficient virus budding.

PMID- 8131741
TI  - The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible
      fashion.
AB  - Nuclear bodies (NBs) are ultrastructurally defined granules predominantly found
      in dividing cells. Here we show that PML, a protein involved in the t(15;17)
      translocation of acute promyelocytic leukaemia (APL), is specifically bound to a
      NB. PML and several NB-associated proteins, found as auto-antigens in primary
      biliary cirrhosis (PBC), are co-localized and co-regulated. The APL-derived PML
      RAR alpha fusion protein is shown to be predominantly localized in the cytoplasm,
      whereas a fraction is nuclear and delocalizes the NB antigens to multiple smaller
      nuclear clusters devoid of ultrastructural organization. RA administration (which
      in APL patients induces blast differentiation and consequently complete
      remissions) causes the re-aggregation of PML and PBC auto-antigens onto the NB,
      while PML-RAR alpha remains mainly cytoplasmic. Thus, PML-RAR alpha expression
      leads to a RA-reversible alteration of a nuclear domain. These results shed a new
      light on the pathogenesis of APL and provide a molecular link between NBs and
      oncogenesis.

PMID- 8131742
TI  - Mutation of the endogenous p53 gene in cells transformed by HPV-16 E7 and EJ c
      ras confers a growth advantage involving an autocrine mechanism.
AB  - Rat embryo fibroblasts transformed with the HPV-16 E7 gene and the activated c-H
      ras gene fall into two distinct phenotypic classes. At high cell density, clones
      of one class form colonies in methylcellulose supplemented with low serum; at low
      cell density, these cells display responsiveness to mitogenic factors present in
      serum-free conditioned medium from rat embryo fibroblasts. In contrast, clones of
      the second class exhibit an absolute dependency on growth factors present in
      serum at all cell densities in the methylcellulose colony assay and fail to
      respond to conditioned medium. We find that the status of the endogenous p53 gene
      is tightly correlated with these two classes of clones. Clones of the first class
      contain missense mutations in the p53 gene and have lost the wild-type allele.
      Clones of the second class express wild-type p53 protein. The importance of
      mutant p53 expression in reducing the growth factor dependency of transformed
      clones was confirmed in a separate series of experiments in which rat embryo
      fibroblasts were transformed with three genes, E7 + ras + mutant p53. The growth
      behaviour of these triply transfected clones was similar to that of the E7 + ras
      clones expressing endogenous mutant p53. We demonstrate that the enhanced
      proliferation of E7 + ras clones expressing mutant p53 protein involves an
      autocrine mechanism.

PMID- 8131743
TI  - Activation of the cell cycle machinery and the isoflavonoid biosynthesis pathway
      by active Rhizobium meliloti Nod signal molecules in Medicago microcallus
      suspensions.
AB  - We have shown that treatment of Medicago microcallus suspensions with the cognate
      Rhizobium meliloti Nod signal molecule NodRm-IV(C16:2,S) can modify gene
      expression both qualitatively and quantitatively. At concentrations of 10(-6) -
      10(-9) M, this host specific plant morphogen but not the inactive non-sulfated
      molecule stimulated cell cycle progression as indicated by the significantly
      enhanced thymidine incorporation, elevated number of S phase cells, increase in
      kinase activity of the p34cdc2-related complexes and enhancement of the level of
      expression of several cell cycle marker genes, the histone H3-1, the cdc2Ms and
      the cyclin cycMs2. The presented data suggest that at least part of the
      physiological role of the Nod factor may be linked to molecular events involved
      in the control of the plant cell division cycle. In situ hybridization
      experiments with antisense H3-1 RNA probe indicated that only certain cells of
      the calli were able to respond to the Nod factor. High (10(-6) M) but not low
      (10(-9) M) concentrations of the active Nod factors induced the expression of the
      isoflavone reductase gene (IFR), a marker gene of the isoflavonoid biosynthesis
      pathway in most callus cells. Our results indicate that Medicago cell responses
      to the Nod signal molecules can be investigated in suspension cultures.

PMID- 8131744
TI  - The Dbf2 and Dbf20 protein kinases of budding yeast are activated after the
      metaphase to anaphase cell cycle transition.
AB  - Thermosensitive mutations in the DBF2 gene arrest the cell cycle during nuclear
      division. Although the chromatin has divided in arrested cells, an elongated
      mitotic spindle is present and Cdc28 protein kinase activity remains high,
      indicating that nuclear division is incomplete. By execution point analysis we
      show that Dbf2 carries out an essential cell cycle function after the metaphase
      to anaphase transition and is therefore required during anaphase and/or
      telophase. This cell cycle stage-specific requirement for the function of Dbf2
      coincides with the cell cycle regulation of Dbf2/Dbf20 protein kinase activity,
      which can be detected in immunoprecipitates containing Dbf2 or Dbf20. The kinase
      activity is specific for serine/threonine residues and Dbf2 accounts for the bulk
      of the activity, with Dbf20 playing a minor role. Furthermore, Dbf2 is a
      phosphoprotein and, significantly, the dephosphorylated form appears with the
      same cell cycle timing as the kinase activity, suggesting a role for
      dephosphorylation in the activation mechanism. In addition, we show that the DBF2
      transcript, which is under cell cycle control, is expressed in advance of the
      activation of the kinase, but that cell cycle-regulated expression of the mRNA is
      not required for activation of the Dbf2 kinase during M phase. Thus, Dbf2/Dbf20
      kinase activity is precisely regulated in the cell cycle by a post-translational
      mechanism and phosphorylates its target substrates for an event that occurs
      during anaphase and/or telophase.

PMID- 8131745
TI  - Cell cycle-dependent regulation of the phosphorylation and metabolism of the
      Alzheimer amyloid precursor protein.
AB  - Accumulation of the amyloid A beta peptide, which is derived from a larger
      precursor protein (APP), and the formation of plaques, are major events believed
      to be involved in the etiology of Alzheimer's disease. Abnormal regulation of the
      metabolism of APP may contribute to the deposition of plaques. APP is an integral
      membrane protein containing several putative phosphorylation sites within its
      cytoplasmic domain. We report here that APP is phosphorylated at Thr668 by
      p34cdc2 protein kinase (cdc2 kinase) in vitro, and in a cell cycle-dependent
      manner in vivo. At the G2/M phase of the cell cycle, when APP phosphorylation is
      maximal, the levels of mature APP (mAPP) and immature APP (imAPP) do not change
      significantly. However, imAPP is altered qualitatively. Furthermore, the level of
      the secreted extracellular N-terminal domain (APPS) is decreased and that of the
      truncated intracellular C-terminal fragment (APPCOOH) is increased. These
      findings suggest the possibility that phosphorylation-dependent events occurring
      during the cell cycle affect the metabolism of APP. Alterations in these events
      might play a role in the pathogenesis of Alzheimer's disease.

PMID- 8131746
TI  - Activation of MEK family kinases requires phosphorylation of two conserved
      Ser/Thr residues.
AB  - MEK is a family of dual specific protein kinases which activate the extracellular
      signal-regulated kinases by phosphorylation of threonine and tyrosine residues.
      MEK itself is activated via serine phosphorylation by upstream activator kinases,
      including c-raf, mos and MEK kinase. Here, we report the activation
      phosphorylation sites of human MEK1 and yeast STE7 kinase as determined by a
      combination of biochemical and genetic approaches. In human MEK1, substitution of
      either serine residue 218 or 222 with alanine completely abolished its activation
      by epidermal growth factor-stimulated Swiss 3T3 cell lysates or
      immunoprecipitated c-raf, suggesting that both serine residues are required for
      MEK1 activation. Phosphopeptide analysis demonstrated that serine residues 218
      and 222 of human MEK1 are the primary sites for phosphorylation by c-raf. These
      two serine residues are highly conserved in all members of the MEK family,
      including the yeast STE7 gene product, a MEK homolog in the yeast mating
      pheromone response pathway. Mutation of the corresponding residues in STE7
      completely abolished the biological functions of this gene. These data
      demonstrate that MEK is activated by phosphorylation of two adjacent
      serine/threonine residues and this activation mechanism is conserved in the MEK
      family kinases.

PMID- 8131747
TI  - Targeted disruption of the CD3 eta locus causes high lethality in mice:
      modulation of Oct-1 transcription on the opposite strand.
AB  - CD3 zeta and eta chains are components of the T cell antigen receptor (TCR)
      complex and are transcribed from a common gene by alternative splicing. TCR
      complexes containing the zeta eta dimer have been thought to mediate different
      functions than complexes containing the zeta 2 dimer. To analyze the role of eta
      in the development and function of T cells, we generated eta-deficient mice
      without affecting zeta by gene targeting in embryonic stem cells. Homozygous
      mutant embryos developed normally. Unexpectedly, however, these mice exhibited
      high mortality soon after birth for unknown reason(s). Analysis of surviving
      homozygous animals revealed that the development and function of T cells were
      normal in the absence of the eta chain. Recently, the zeta/eta locus was reported
      to encode a transcription factor, Oct-1, on the opposite DNA strand. Our
      targeting strategy resulted in modulation of Oct-1 transcription--reduction of
      the authentic Oct-1 mRNA and induction of aberrant transcripts. Although
      differences in tissue distribution and DNA binding capacity of Oct-1 between wild
      type and eta-deficient mice were not evident from in situ hybridization and gel
      shift analysis, the high mortality in the eta-deficient strain may well be due to
      the disturbance of Oct-1 transcription by the mutation in the zeta/eta locus.
      Such possible complexities have to be taken into account in the interpretation of
      gene targeting experiments.

PMID- 8131748
TI  - Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA
      isoforms coding for either secreted or membrane-bound proteins related to the IL
      1 receptor.
AB  - Fit-1 has been identified previously as a Fos-responsive gene of rat fibroblasts.
      Here we show that Fit-1 is directly regulated by the estrogen-inducible
      transcription factor Fos-ER and that it belongs to the family of delayed early
      genes. Two different mRNA isoforms are expressed from the Fit-1 gene. The Fit-1M
      mRNA isolated from spleen codes for a membrane-bound protein which is most
      closely related in its extracellular, transmembrane and intracellular domains to
      the type I interleukin-1 (IL-1) receptor. The Fit-1S mRNA of fibroblasts directs,
      instead, the synthesis of a secreted protein consisting of only the extracellular
      domain. Analysis of the exon-intron structure of the Fit-1 gene indicated that
      the Fit-1S and Fit-1M mRNAs are transcribed from two different promoters and that
      the sequence differences at their 3' ends result from alternative 3' processing.
      Northern blot analysis with specific 5' and 3' probes directly demonstrated tight
      coupling between alternative promoter usage and 3' processing of the Fit-1
      transcripts. The orthologous gene of the mouse (known as T1 or ST2) is expressed
      during ontogeny first in the fetal liver of the embryo and then in lung and
      hematopoietic tissues of the adult. The mRNA coding for the membrane-bound
      protein is more abundantly expressed in all of these tissues, while the
      transcript for the secreted form predominates in fibroblasts and mammary
      epithelial cells. Differential regulation of two distinct promoters is thus used
      to determine the ratio between secreted and membrane-bound forms of Fit-1
      (T1/ST2) which may modulate signaling in response to IL-1.

PMID- 8131749
TI  - Interleukin-6 deficient mice are protected from bone loss caused by estrogen
      depletion.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine whose circulating levels are
      under physiological conditions below detection, but whose production is rapidly
      and strongly induced by several pathological and inflammatory stimuli. IL-6 has
      been implicated in a number of cell functions connected to immunity and
      hematopoiesis. Recently, it has been proposed to act as a stimulator of
      osteoclast formation and activity, in particular following estrogen depletion.
      The purpose of this study was to gain additional insights into the role of IL-6
      during development, as well as in physiological and pathological conditions. We
      report here that IL-6 deficient mice generated by gene targeting are viable and
      do not present any evident phenotypic abnormality. However, analysis of bone
      metabolism revealed a specific bone phenotype. IL-6 deficient female mice have a
      normal amount of trabecular bone, but higher rates of bone turnover than control
      littermates. Estrogen deficiency induced by ovariectomy causes in wild type
      animals a significant loss of bone mass together with an increase in bone
      turnover rates. Strikingly, ovariectomy does not induce any change in either bone
      mass or bone remodeling rates in the IL-6 deficient mice. These findings indicate
      that IL-6 plays an important role in the local regulation of bone turnover and,
      at least in mice, appears to be essential for the bone loss caused by estrogen
      deficiency.

PMID- 8131750
TI  - Dominant negative mutants of mammalian translation initiation factor eIF-4A
      define a critical role for eIF-4F in cap-dependent and cap-independent initiation
      of translation.
AB  - Eukaryotic translation initiation factor-4A (eIF-4A) plays a critical role in
      binding of eukaryotic mRNAs to ribosomes. It has been biochemically characterized
      as an RNA-dependent ATPase and RNA helicase and is a prototype for a growing
      family of putative RNA helicases termed the DEAD box family. It is required for
      mRNA-ribosome binding both in its free form and as a subunit of the cap binding
      protein complex, eIF-4F. To gain further understanding into the mechanism of
      action of eIF-4A in mRNA-ribosome binding, defective eIF-4A mutants were tested
      for their abilities to function in a dominant negative manner in a rabbit
      reticulocyte translation system. Several mutants were demonstrated to be potent
      inhibitors of translation. Addition of mutant eIF-4A to a rabbit reticulocyte
      translation system strongly inhibited translation of all mRNAs studied including
      those translated by a cap-independent internal initiation mechanism. Addition of
      eIF-4A or eIF-4F relieved inhibition of translation, but eIF-4F was six times
      more effective than eIF-4A, whereas eIF-4B or other translation factors failed to
      relieve the inhibition. Kinetic experiments demonstrated that mutant eIF-4A is
      defective in recycling through eIF-4F, thus explaining the dramatic inhibition of
      translation. Mutant eIF-4A proteins also inhibited eIF-4F-dependent, but not eIF
      4A-dependent RNA helicase activity. Taken together these results suggest that eIF
      4A functions primarily as a subunit of eIF-4F, and that singular eIF-4A is
      required to recycle through the complex during translation. Surprisingly, eIF-4F,
      which binds to the cap structure, appears to be also required for the translation
      of naturally uncapped mRNAs.

PMID- 8131751
TI  - Stch encodes the 'ATPase core' of a microsomal stress 70 protein.
AB  - The stress70 protein chaperone family plays a central role in the processing of
      cytosolic and secretory proteins. We have cloned a human cDNA, designated Stch,
      that is conserved in rat tissues and which encodes a novel microsome-associated
      member of the stress70 protein chaperone family. Stch mRNA is constitutively
      expressed in all human cell types and is induced by incubation with the calcium
      ionophore A23187, but not by exposure to heat shock. Inspection of the predicted
      amino acid sequence reveals that the STCH product contains a unique hydrophobic
      leader sequence and shares homology within the amino terminal domains of the
      stress70 gene family, but has a 50 residue insertion within the ATP-binding
      domains and truncates the carboxyl terminal peptide-binding region.
      Immunofluorescent and subcellular analyses show that STCH migrates predominantly
      as a 60 kDa species and is enriched in a membrane-bound microsome fraction. In
      contrast to purified BiP and dnaK, however, STCH demonstrates ATPase activity
      that is independent of peptide stimulation. Stch, therefore, encodes a calcium
      inducible, microsome-associated ATPase activity with properties similar to a
      proteolytically cleaved N-terminal HSC70/BiP fragment. This truncated stress70
      molecule may allow increased diversity in cellular responses to protein
      processing requirements.

PMID- 8131752
TI  - In vivo assembly of active maltose binding protein from independently exported
      protein fragments.
AB  - The maltose binding protein (MBP or MalE) of Escherichia coli is the periplasmic
      component of the transport system for malto-oligosaccharides. It is synthesized
      in the cytoplasm with an N-terminal signal peptide that is cleaved upon export.
      We examined whether active MBP could assemble into an active protein in bacteria,
      from N- and COOH-terminal complementary protein fragments encoded by distinct,
      engineered segments of its structural gene. We found export and functional
      periplasmic assembly of MBP fragments, despite the complex polypeptide chain
      topology of this protein, if two conditions were satisfied. First, each of the
      two fragments must carry a signal peptide. Second, the boundaries between the two
      fragments must correspond to a permissive site within the protein. Functional
      assembly of active MBP occurred in five cases where these conditions were met:
      sites after residues 133, 161, 206, 285 and 303; but not in three other cases
      where the break junction corresponded to a non-permissive site: after residues
      31, 120 and 339. Thus, permissive sites which were initially characterized
      because they could accept extensive genetic insertion/deletion modifications
      without loss of most biological properties provide a means of defining
      complementing protein fragments. This observation opens a way to study
      genetically the relationships between protein export and folding into the
      periplasm.

PMID- 8131754
TI  - Potassium channel blockade and acute myocardial infarction: implications for
      management of the non-insulin requiring diabetic patient.

PMID- 8131753
TI  - The characterization of a mammalian DNA structure-specific endonuclease.
AB  - The repair of some types of DNA double-strand breaks is thought to proceed
      through DNA flap structure intermediates. A DNA flap is a bifurcated structure
      composed of double-stranded DNA and a displaced single-strand. To identify DNA
      flap cleaving activities in mammalian nuclear extracts, we created an assay
      utilizing a synthetic DNA flap substrate. This assay has allowed the first
      purification of a mammalian DNA structure-specific nuclease. The enzyme described
      here, flap endonuclease-1 (FEN-1), cleaves DNA flap strands that terminate with a
      5' single-stranded end. As expected for an enzyme which functions in double
      strand break repair flap resolution, FEN-1 cleavage is flap strand-specific and
      independent of flap strand length. Furthermore, efficient flap cleavage requires
      the presence of the entire flap structure. Substrates missing one strand are not
      cleaved by FEN-1. Other branch structures, including Holliday junctions, are also
      not cleaved by FEN-1. In addition to endonuclease activity, FEN-1 has a 5'-3'
      exonuclease activity which is specific for double-stranded DNA. The endo- and
      exonuclease activities of FEN-1 are discussed in the context of DNA replication,
      recombination and repair.

PMID- 8131755
TI  - The epidemiology of right bundle branch block and its association with
      cardiovascular morbidity--the Reykjavik Study.
AB  - This study is based on the Reykjavik Study, a long-term prospective
      cardiovascular survey, which included a representative population of 9135 men and
      9627 women, 33-79 years old, who were invited to participate during the years
      1967-91. Right bundle branch block (RBBB) was found in 126 men and 67 women. The
      prevalence increased with age, from 0% among men and women 30-39 years of age to
      4.1% and 1.6% in men and women, respectively, who where 75-79 years old. The
      incidence increased with age. In men younger than 60 years RBBB had a significant
      relationship with hypertension (P < 0.05), elevated fasting blood glucose (P =
      0.05), and increased heart size (P < 0.05). In men with RBBB regardless of age,
      an association was found with cardiomegaly (P < 0.05), ischaemic heart disease (P
      < 0.05), arrhythmias (P < 0.001) and bradycardia (P < 0.01). A higher mortality
      from heart disease (P < 0.01) was found in men with RBBB compared to the control
      population. This was not significant when risk factors of heart disease were
      taken into account by multivariate Cox analysis. There was a relationship (P <
      0.05) between hypertension and RBBB in women younger than 60 years. RBBB in women
      younger than 60 years is often associated with hypertension and in men younger
      than 60 it is often associated with an underlying cardiovascular disease,
      hypertension, cardiomegaly and elevated blood glucose.

PMID- 8131756
TI  - Pulmonary venous flow pattern studied by transoesophageal pulsed Doppler
      echocardiography in mitral stenosis in sinus rhythm: effect of atrial systole.
AB  - In 13 patients with isolated mitral stenosis in sinus rhythm the pulmonary venous
      flow was evaluated by transoesophageal pulsed Doppler echocardiography. The
      patients were divided into two groups according to their mitral valve area (MVA);
      Group I (MVA < 1.5 cm2, n = 7 patients); and Group II (MVA > 1.5 cm2, n = 6). The
      patients in group I with haemodynamically significant mitral stenosis had lower
      velocities of systolic (S), diastolic (D) and atrial retrograde (A) waves of
      pulmonary venous flow (PVF) compared to milder stenosis (P < 0.05). The peak
      velocity of pulmonary retrograde venous flow at atrial contraction (A) primarily
      depends on the relative amplitude of the atrial transmitral wave (RA), which is
      measured from the onset of atrial systole to its peak velocity. We found a highly
      positive correlation between RA of mitral valve flow (MVF) and A wave of PVF (r =
      0.87, P < 0.0001). There was also a highly negative correlation (r = 0.80, P <
      0.001) between A of PVF and ratio of early (PE) to late (PA) velocities of MVF.
      Therefore, the retrograde A wave of PVF is related to the pressure generated in
      the left atrium during atrial systole. Use of pulmonary vein velocities in
      conjunction with mitral flow velocities can increase our understanding of the
      haemodynamics of mitral stenosis and provide a new insight into left atrial
      performance.

PMID- 8131757
TI  - Doppler haemodynamic assessment of clinically and echocardiographically normal
      mitral and aortic Allcarbon valve prostheses. Valve Prostheses Ligurian
      Cooperative Doppler Study.
AB  - Doppler echocardiographic characteristics of normally functioning Allcarbon
      prostheses were studied in 149 consecutive patients with 157 valves in the mitral
      (n = 73) and aortic (n = 84) positions whose function was considered normal by
      clinical and echocardiographic evaluation. In the mitral position, the mean
      gradient and the effective mitral orifice area were not significantly different
      in either the 25-mm or the 31-mm size valves (from 5 +/- 1 to 4 +/- 1 mmHg and
      from 2.2 +/- 0.6 to 2.8 +/- 0.9 cm2, respectively; P = ns for both). Conversely,
      peak gradient was significantly and inversely correlated to actual orifice area
      (r = -0.70; P < 0.0006), decreasing from 15 +/- 3 mmHg in the 25-mm size valve to
      9 +/- 1 mmHg in the 31-mm size. In the aortic position, the mean gradient was 29
      +/- 8 mmHg in the 19-mm size valve; it decreased to 8 +/- 2 mmHg in the 29-mm
      size. Effective prosthetic aortic valve area, calculated using the continuity
      equation, ranged between 0.9 +/- 0.1 cm2 for the 19-mm size valve to 4.1 +/- 0.7
      cm2 for the 29-mm size. By analysis of variance, effective prosthetic aortic
      valve area differentiated various valve sizes (F = 25.3; P < 0.0001) better than
      peak (F = 5.34; P = 0.012) or mean (F = 4.34; P = 0.0052) gradients alone, and it
      correlated better with actual orifice area (r = 0.89, r = -0.70 and r = -0.65,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131758
TI  - Neuroendocrine activation and markers of early reperfusion in the acute phase of
      myocardial infarction.
AB  - Potentially harmful stimulation of the neuroendocrine axis occurs in the early
      hours of myocardial infarction. It has been suggested that this acute
      neuroendocrine response might be attenuated by early therapeutic reperfusion. To
      test this hypothesis we measured plasma concentrations of atrial natriuretic
      factor (ANF), renin, adrenaline (ADR) and noradrenaline (NADR) on admission and
      at 1 h and 4 h in 32 patients undergoing streptokinase treatment within 6 h of
      myocardial infarction. Fractional changes (FC) in hormone levels were calculated:
      e.g. ANFO-ANF4/ANFO. Resolution of ST segment elevation at 4 h was the primary
      measure of reperfusion. Sixteen patients showed ST segment resolution. There was
      no difference in hormone levels at baseline between reperfused and non-reperfused
      patients. Fractional changes in ANF, renin and ADR were similar in both groups.
      NADR fell from admission to 4 h in reperfused patients but rose in non-reperfused
      (FC 0.28 vs -0.10; P = 0.054). There was no difference in the changes in pulse
      rate or blood pressure from admission to 4 h between the two groups. Thus there
      is no evidence that early reperfusion acutely alters the release of ANF, renin or
      ADR to myocardial infarction. Although plasma NADR tended to fall acutely in
      reperfused patients this was not accompanied by other markers of sympathetic
      withdrawal.

PMID- 8131759
TI  - Left ventricular hypertrophy and myocardial ischaemia in hypertension: the THAMES
      Study.
AB  - A multicentre epidemiological study to detect the prevalence of myocardial
      ischaemia in hypertensive left ventricular hypertrophy (LVH) was performed in 188
      asymptomatic male hypertensives (131 treated). The mean age was 55 (range 40-82)
      years with blood pressure (BP) > or = 160/100 mmHg or a systolic BP > or = 180
      mmHg. The participants were screened with echocardiography, and left ventricular
      hypertrophy (LVH), defined as LV mass index (LVMI) > or = 130 g.m-2, was found in
      127 (68%), of whom 95 were on antihypertensive treatment. Patients with LVH
      underwent a maximal bicycle ergometer exercise test and significant ST
      depression, indicating possible stress-induced ischaemia, was found in 29 men
      (23%). These subjects were subjected to exercise thallium-201 scintigraphy, which
      was normal in 14 but showed reversible perfusion defects in 15. Thus, a high
      prevalence of LVH (70%) was detected in male hypertensives selected only on age
      and BP. In addition, although chest pain on exertion excluded patients from
      entry, a substantial portion had signs of ischaemia (23% on exercise ECG alone,
      and in 52% confirmed by thallium scan). The prevalence of these risk factors
      should be considered when evaluating hypertensive patients.

PMID- 8131760
TI  - Two types of left ventricular wall motion abnormalities with distinct clinical
      features in patients with hypertrophic cardiomyopathy.
AB  - During the long-term follow-up of patients with hypertrophic cardiomyopathy
      (HCM), some patients develop left ventricular (LV) wall motion abnormalities in
      the absence of fixed coronary artery disease. The purpose of this study is to
      clarify which clinical features in patients with HCM seem to influence gradual
      development of LV wall motion abnormalities over an extended period of time. The
      study investigates the incidence, mechanism and predictors of these
      abnormalities. In this retrospective study of 162 patients with HCM, followed-up
      for an average of 13.3 years, we focused our attention on 16 patients who
      gradually developed two different forms of LV wall motion abnormality. In 11 of
      these 16 patients, apical segmental dysfunction with midzone obstruction was
      recognized; the remaining five patients showed generalized hypokinesis, as seen
      in dilated cardiomyopathy. The 11 patients with apical segmental dysfunction
      presented with extensive apical hypertrophy reaching the midventricular level at
      first examination. The five patients with generalized hypokinesis showed a slight
      decrease in LV contractility and reduced localized antero-apical wall motion even
      at initial examination. None of the patients in either group developed the other
      group's features during their clinical course. These two groups had different
      initial manifestations and pursued different clinical courses, suggesting that
      the underlying mechanisms causing wall motion abnormalities are different.

PMID- 8131761
TI  - Hypersensitivity reactions to streptokinase in patients with high pre-treatment
      antistreptokinase antibody and neutralisation titres.
AB  - After streptokinase or antistreplase administration, raised antibody levels can
      persist for many years, but it is unclear if these antibodies can cause allergic
      reactions following streptokinase re-administration for myocardial re-infarction.
      Pretreatment antistreptokinase antibody (AB) and neutralisation titres (NT) were
      measured in 189 consecutive patients (57 received streptokinase or anistreplase).
      Seven patients had previous exposure to streptokinase or anistreplase; they had
      high mean (SEM) antibody titres of 1:801 (332) and neutralisation titres of 3.3
      (1.7) million units. The 182 patients without previous thrombolysis had mean (SD)
      antibody titres of 1:25 (3) and neutralisation titres of 0.14 (0.08) million
      units; nine patients (4.95%), however, had raised antibody titres of > or = 1:160
      and neutralisation titres of > or = 0.3 million units. Of the 15 patients with
      antibody titres of > or = 1:160, three received streptokinase or anistreplase.
      Hypersensitivity reactions occurred in all three patients--neutralisation titres
      0.48, 1.5 and 1.1 million units respectively. Two became severely hypotensive
      with systolic pressures of 70 mmHg; one developed a serum sickness-like reaction.
      Importantly, none of the 54 patients with antibody titres of < 1:160 who received
      streptokinase or antistreplase reacted adversely to the thrombolytic agents (chi
      2 with Yates's correction = 38.71, P < 0.01). High antibody titres are associated
      with hypersensitivity reactions to streptokinase. This has important implications
      in reinfarction thrombolysis. In patients whose antistreptokinase antibody titres
      are likely to be raised the avoidance of streptokinase-related thrombolytic
      agents should be considered.

PMID- 8131762
TI  - The Multicentre European Radiofrequency Survey (MERFS): complications of
      radiofrequency catheter ablation of arrhythmias. The Multicentre European
      Radiofrequency Survey (MERFS) investigators of the Working Group on Arrhythmias
      of the European Society of Cardiology.
AB  - Radiofrequency (RF) catheter ablation has developed into a new non
      pharmacological therapy for the definitive treatment of patients with cardiac
      arrhythmias. Although an increasing number of recent reports have indicated the
      widespread use of the procedure, no data are available to estimate the number of
      procedures performed in Europe. Furthermore, currently no data on a large series
      of patients are available that provide information on the risk of procedure
      related complications. This report presents the results of the Multicentre
      European Radiofrequency Survey (MERFS) that was conducted by the Working Group on
      Arrhythmias of the European Society of Cardiology. The objectives of this
      voluntary retrospective survey were to assess the number of radiofrequency
      catheter ablation procedures performed in 86 European institutions from January
      1987 until March 1992 and the incidence of procedure-related complications with
      respect to the different types of ablative procedures. A total of 4398 patients
      were reported on from 68 out of 86 institutions (79%) from 15 European countries
      that agreed to participate in MERFS. From 1987 to 1991, the number of patients
      who underwent RF ablation per year increased from 45 to 2000. In the first 3
      months of 1992, a total of 1640 patients were reported on. The number of patients
      reported on in relation to the different types of ablative procedures were:
      ablation of atrial tachycardialatrial flutter: n = 141 (3.2%); ablation of the
      atrioventricular junction: n = 900 (20.5%); modification of the atrioventricular
      junction in atrioventricular nodal reentrant tachycardia: n = 815 (18.5%);
      ablation of accessory pathway: n = 2222 (50.5%); ablation of ventricular
      tachycardia: n = 320 (7.3%). Procedure-related complications occurred in 223
      patients (5.1%). The incidence of complications in relation to the ablative
      procedure was: ablation of atrial tachycardia/atrial flutter: 5.0%; ablation of
      the atrioventricular junction: 3.2%; modification of the atrioventricular
      junction in atrioventricular nodal reentrant tachycardia: 8.0%; ablation of
      accessory pathway: 4.4%; ablation of ventricular tachycardia: 7.5%. Complications
      occurred significantly more often in patients who underwent modification of the
      atrioventricular junction in atrioventricular nodal reentrant tachycardia, when
      compared to ablation of the atrioventricular junction (P < 0.001) or ablation of
      accessory pathway (P < 0.001), and in patients who underwent ablation of
      ventricular tachycardia, when compared to ablation of the atrioventricular
      junction (P < 0.002) or ablation of accessory pathway (P < 0.02). The highest
      incidence of complications was reported after modification of the
      atrioventricular junction in atrioventricular nodal reentrant
      tachycardia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8131763
TI  - Factors that predict spontaneous remission of ectopic atrial tachycardia.
AB  - Ectopic atrial tachycardia (EAT) is usually considered as benign and easy to
      treat. The natural history of the disease, however, has not yet been clarified.
      The purpose of the study was to analyse its spontaneous evolution in a cohort of
      EAT patients and to define a predictive model of remission based on several
      factors. Between 1973 to 1989, 46 patients (25 male, 21 female), aged 38 +/- 18
      years, entered the study. Clinically EAT was paroxysmal in 23 patients, permanent
      in 12 and repetitive in 11; six patients were asymptomatic. Thirty-five
      complained of palpitations; dyspnoea, dizziness and syncope were also reported
      less frequently. All patients underwent an electrophysiological study to clarify
      the mechanism of the arrhythmia and to localize its site of origin. In 15
      patients no heart disease was documented. Five patients underwent surgery and
      were excluded from subsequent analysis. Seven patients were discharged without
      antiarrhythmic treatment. We defined remission as the absence of recurrence of
      EAT within 6 months from withdrawal of therapy. Logistic regression was applied
      to identify potential predictors of remission. Seven clinical and
      electrophysiological covariates were entered in the model; univariate and
      multivariate tests were performed, using the GLIM3 statistical package. During a
      follow-up period of 5.1 +/- 4.5 years, 14 instances of remission (34%) were
      observed in 5/22 patients with paroxysmal EAT, 4/8 patients with permanent EAT
      and 5/11 patients with repetitive EAT. Mean age of patients with remission was 25
      +/- 14 years vs 45 +/- 15 years in the group without remission. No covariate had
      an independent predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131764
TI  - Balloon valvuloplasty for valvular pulmonary stenosis in children over 6 months
      of age: initial results and long-term follow-up.
AB  - Between 1984 and December 1990 balloon valvuloplasty for valvular pulmonary
      stenosis was planned and performed in 92 children over 6 months of age (range 0.8
      17.9 years). Valvuloplasty decreased the invasively determined peak systolic
      gradient from 61 +/- 34 (mean +/- SD) to 27 +/- 20 mmHg (P < 0.0001). At follow
      up cardiac catheterization, performed in 22 patients after 13 +/- 5 months, the
      gradient was 22 +/- 23 mmHg (ns). Initially the continuous wave Doppler gradient
      decreased from 61 +/- 23 to 26 +/- 12 mmHg (P < 0.0001). It then remained
      unchanged both at early follow-up after 0.6 +/- 0.3 years, being 23 +/- 12 mmHg,
      and at long-term follow-up after 3 +/- 1.7 years (21 +/- 10 mmHg, ns). In the 41
      patients treated before the end of 1986 the residual continuous wave Doppler
      gradient at long-term follow-up after 5.1 +/- 0.8 years was 21 +/- 10 mmHg. Mild
      pulmonary regurgitation was present in 77% of the patients at early follow-up and
      in 83% at the last follow-up. Right ventricular hypertrophy on the
      electrocardiogram was present in 83% of the children before valvuloplasty. At
      early follow-up it had decreased to 44% with a further decrease to 24% at the
      last follow-up. Comparison of patients with initial invasive systolic gradients
      greater and smaller than 50 mmHg revealed no differences between either group
      with regard to the continuous wave Doppler gradient at last follow-up, the
      incidence of pulmonary regurgitation and the occurrence of significant
      complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131765
TI  - PTCA in elderly patients: acute results and long-term follow-up.
AB  - Acute results and long-term follow-up of percutaneous transluminal coronary
      angioplasty (PTCA) in 125 patients aged 75 to 90 years (79 men; 46 female; mean
      age 78 +/- 3 years), with mainly unstable angina (102 patients) are reported.
      Successful PTCA was achieved in 96 out of 108 patients (89%); occlusions could be
      reopened in eight out of 17 patients (47%). Thirty-eight procedures were multiple
      vessel or multiple lesion PTCA, so that the lesion-related success rate of PTCA
      was higher (91%). Major complications occurred in seven patients (5.6%) including
      one procedure-related death. In-hospital mortality was 3% and concerned
      exclusively patients with unstable angina and unsuccessful procedure. At a mean
      follow-up of 27 +/- 16 months (2 to 82 months) 13 additional patients had died:
      10 from cardiovascular causes, three from cancer. In the meantime, three patients
      underwent non-fatal myocardial infarction and three elective bypass surgery; 26
      patients had repeat PTCA. Eighty-seven of the 93 surviving patients with
      successful primary procedure and reintervention if necessary, were in anginal
      class I or II; only six were in class III. We conclude that the success rate of
      PTCA in elderly patients is comparable to that in younger patients, and that a
      successful procedure leads to continued relief of symptoms.

PMID- 8131766
TI  - Apical transgastric echocardiography: new imaging projections.
AB  - New transgastric echocardiographic projections, obtained by monoplane
      transoesophageal echocardiography are presented. Starting from the transgastric
      short-axis view, the probe is first advanced 3-5 cm and slightly rotated
      clockwise. From this projection either a tricuspid valve long-axis or a subcostal
      like 4-chamber view is obtained. Advancing the probe 48-55 cm from the incisor
      teeth and rotating it counter clockwise with maximal anterior flexion, an apical
      long-axis view is obtained. The left ventricle, including the apex, the left
      ventricular outflow tract, the aortic valve, the proximal ascending aorta and the
      left atrium are imaged. In this projection the Doppler beam is parallel to the
      left ventricular outflow tract, resulting in more accurate flow velocity
      measurements than from the oesophagus. Additional morphological and Doppler
      information on right ventricular outflow tract obstruction are obtained by slight
      changes in transducer position. The feasibility of these new transgastric imaging
      projections was assessed in 196 consecutive patients undergoing diagnostic TEE
      (104 conscious patients) or peroperative TEE monitoring (92 anaesthetized
      patients). Eighty-nine patients had coronary heart disease, 55 had valvular heart
      disease, nine had congenital heart disease, 22 had aortic aneurysm or dissection
      and 21 were studied for detection of cardiac sources of embolism. The morphology
      of the right ventricular outflow tract was visualized in detail in all patients,
      and high quality Doppler tracings parallel to the direction of flow were
      obtained. The subcostal-like view was successful in 86 out of 196 subjects (44%).
      The apical 4 and/or 5-chamber view was obtained in 139 subjects (71%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8131767
TI  - Feasibility of assessing regional myocardial uptake of 18F-fluorodeoxyglucose
      using single photon emission computed tomography.
AB  - Differentiation between viable myocardium and scar tissue in segments with
      abnormal contraction has important consequences in the clinical management of
      patients with coronary artery disease. Positron emission tomography (PET) can
      identify viable tissue using 18F-fluorodeoxyglucose (FDG). However, application
      of PET for daily routine is limited. In this study, FDG uptake was visualized
      with single photon emission computed tomography (SPECT) and compared with
      regional perfusion assessed with thallium-201 (201Tl) SPECT. The scintigraphic
      findings were related to regional wall motion determined with two-dimensional
      echocardiography. Patients (n = 9) with wall motion abnormalities underwent FDG
      SPECT and resting 201Tl SPECT. To control the metabolic status patients were
      studied with a hyperinsulinaemic euglycemic clamp during FDG SPECT. Analysis of
      reconstructed data was performed visually and semiquantitatively using
      circumferential profiles. High-quality images were obtained. Eight 201Tl defects
      showed concordantly decreased FDG uptake (metabolism-perfusion matches)
      indicating scarred tissue, whereas six regions of hypoperfusion demonstrated a
      relatively increased FDG uptake (mismatches), suggesting viable myocardium.
      Semiquantitative analysis confirmed visual findings. Mean 201Tl and FDG
      activities were not significantly different in matching defects. In mismatches
      the mean FDG activity was 81 +/- 11% vs 64 +/- 9% mean 201Tl activity (P <
      0.0001). In four of six segments with increased FDG uptake, two-dimensional echo
      revealed hypokinesia. Seven of eight regions with a matching defect in contrast
      were akinetic. Thus, in the areas with a mismatch contractility was preserved. We
      conclude that FDG uptake can be visualized with SPECT. Furthermore, our
      preliminary observations suggest that this approach can identify viable tissue.

PMID- 8131768
TI  - The electrocardiographic diagnosis of regional pericarditis in acute inferior
      myocardial infarction.
AB  - The diagnosis of postinfarction localized (regional) pericarditis has remained
      elusive. During the course of a recent study of patients with fatal free-wall
      rupture, an atypical pattern of T-wave evolution was observed during the days
      preceding death. It was learned, from autopsy examination, that these
      electrocardiographic changes were due to the associated localized pericarditis,
      rather than the rupture, per se. Therefore, this investigation was undertaken to
      ascertain if the same atypical T-wave changes occur in patients with
      postinfarction localized pericarditis, but without free-wall rupture, and to
      determine if the frequency of those changes differs between those patients with
      inferior and those with anterior postinfarction pericarditis. Forty-three
      patients with regional postinfarction pericarditis were identified clinically.
      They were divided into three groups, anterior (17), inferior (17) and lateral or
      posterior (9) myocardial infarction. In this report those patients with anterior
      regional postinfarction pericarditis are compared with those with inferior
      postinfarction pericarditis. It was found that an atypical T-wave evolution
      pattern--either persistently positive T-waves after 48 h or reversal of initially
      inverted T-waves after 48 h--existed in every patient irrespective of infarct
      location. However, the two atypical patterns of T-wave evolution occurred with
      distinctly different frequencies between the two sites of infarction. With
      inferior postinfarction pericarditis, gradual reversal of initially inverted T
      waves occurred in 14 patients (82%) while only three (18%) had persistently
      positive T-waves. Conversely, among patients with anterior postinfarction
      pericarditis, reversal after inversion occurred in five of 17 patients (29%)
      while 12 of 17 patients (71%) had persistently positive deflections (P <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131769
TI  - The effects of early captopril treatment on left ventricular volumes and function
      in patients with and without depressed global ejection fraction after acute
      myocardial infarction.
AB  - To determine the effects of captopril on left ventricular volumes and function in
      patients with and without depressed ventricular function following acute
      myocardial infarction (AMI) we studied 78 patients with a first Q wave AMI and no
      clinical evidence of heart failure. All patients underwent radionuclide
      ventriculography (RVG) on the 4th day after admission and were then randomly
      assigned to receive conventional treatment alone (36 patients, control group) or
      with the addition of oral captopril, 25 mg three times daily (42 patients,
      captopril group). RVG was repeated one month after the baseline examination.
      After one month the left ventricular ejection fraction (LVEF) significantly
      increased in the captopril group (from 43.2 +/- 1.3 to 50.9 +/- 1.6%, P < 0.001)
      and remained relatively unchanged in the control group (from 47 +/- 1.3 to 49.2
      +/- 1.7%, P = ns). In the captopril group the subgroup of patients with a
      baseline LVEF < 45% demonstrated a significant decrease in end-systolic volume
      index (ESVI) (from 53.3 +/- 3.2 to 42.4 +/- 2.8 ml. m-2, P < 0.002) and a highly
      significant improvement in LVEF (from 36.3 +/- 1.3 to 49.6 +/- 1.8%, P <
      0.00005). In the control group, LVEF also increased in those in whom it was < 45%
      (from 38 +/- 1.4 to 42 +/- 2.4%, P < 0.01), but the increase was less than that
      in the captopril group (P < 0.01), mainly due to an increase in end-diastolic
      volume index (EDVI) (from 78.2 +/- 4.6 to 84.6 +/- 12.3 ml.m-2, P = ns).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8131770
TI  - Effects of transdermal nitroglycerin in combination with an ACE inhibitor in
      patients with chronic stable angina pectoris.
AB  - We have previously shown that transdermal nitroglycerin may induce an increase in
      the activity of the adrenergic and the renin-angiotensin-aldosterone systems
      (SRAA) in patients with chronic stable angina pectoris (SA); when the activation
      of these systems is more pronounced, the antianginal effect of this drug seems to
      be reduced. The aim of this study was to evaluate the antianginal efficacy of
      transdermal nitroglycerin administration (TTS-NG 10 mg.24 h-1) in combination
      with an ACE inhibitor without sulphydryl groups (BNZ, benazepril 10 mg b.i.d.) in
      respect to placebo, or to TTS-NG or BNZ administered as monotherapy. Twenty-four
      patients (21M, 3F) were admitted to this multicentre, randomized, double-blind,
      latin square, placebo-controlled study. Patients received all the treatments
      (placebo, TTS-NG, BNZ and BNZ + TTS-NG) each for one week; at the end of each
      week patients performed two exercise tests 2 and 22 h post-dosing. Two hours post
      dosing, exercise duration at 1 mm ST depression was significantly increased in
      respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05)
      treatments. Two hours post-dosing, exercise duration at peak exercise was also
      increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P <
      0.05); 22 h post-dosing the increase in exercise duration was significant only
      during TTS-NG + BNZ treatment (P < 0.05) in respect to placebo, but not during
      TTS-NG given alone. Rate-pressure product at 1 mm ST depression was significantly
      increased 2 h post-dosing during TTS-NG treatment (P < 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8131771
TI  - Myocardial infarction and nicotine patch: a contributing or causative factor?
AB  - A case of angina pectoris revealed by nicotine patch treatment is described in a
      patient who continued to smoke and subsequently suffered a myocardial infarction.
      The various side effects of nicotine and its derivatives are recalled. The action
      of nicotine on coronary vasomotricity and its mediators is discussed.

PMID- 8131772
TI  - Cardiac involvement in Churg-Strauss syndrome: a follow-up of three cases.
AB  - Three cases of Churg-Strauss syndrome with myocardial involvement are reported.
      Cardiac disease is known to be the major cause of death in Churg-Strauss
      syndrome. Aggressive therapy (steroids and cyclophosphamide) may cure the
      myocardial dysfunction associated with the disease.

PMID- 8131773
TI  - Aneurysm of the interventricular membranous septum with thrombo-embolism--an
      indication for surgical repair?
AB  - A 40-year-old woman with a significant neurological history presented with right
      hemiparesia, paraesthesia of the right upper member and of the hemiface. Computer
      tomography scanning revealed hypodensity along the right lateral ventricle which
      corresponded to the left hemiplegia which had developed when she was 20 years
      old. Arteriography of the four cervical axes was normal. Echocardiography
      visualized an aneurysm of the membraneous septum free of thrombosis without
      ventricular septal defect. The embolism was thought to be of cardiac origin and a
      decision was taken to correct it by surgery. Ten years after surgical repair no
      other neurological event has occurred.

PMID- 8131774
TI  - Transthoracic and transoesophageal echocardiography in the diagnosis and
      management of a biatrial myxoma.
AB  - A 40-year-old female presented with a year's history of atrial fibrillation.
      Transthoracic echocardiography identified the presence of a biatrial mass and
      transoesophageal echocardiography delineated its extent. At surgery, a huge
      myxoma originating from the fossa ovalis and straddling the inter-atrial septum
      was removed and the atrial septum repaired. This report highlights the role of
      transthoracic and transoesophageal echocardiography in the diagnosis and
      management of this extremely rare cardiac tumour.

PMID- 8131775
TI  - Carcinoid heart disease: two cases of left heart involvement diagnosed by
      transthoracic and transoesophageal echocardiography.
AB  - We report two observations of significant left heart involvement in patients with
      the carcinoid syndrome assessed by transthoracic and transoesophageal
      echocardiography. Echocardiographic lesions of this kind have only been reported
      twice. In the present cases, there was mitral involvement with mitral
      regurgitation in one case and a mitro-aortic involvement with mitral and aortic
      regurgitation in the other. The mechanism of left heart lesions is unclear since
      in both cases no right-to-left cardiac shunt was present, as attested by colour
      Doppler and saline contrast transoesophageal echocardiography. The location of
      the primary tumour was unknown in one case and ileal in the other; no pulmonary
      metastasis was detected. The use of transoesophageal echocardiography might make
      it possible to detect left-sided cardiac lesions more frequently since they were
      found in anatomical series, in 30% of patients with carcinoid syndrome.

PMID- 8131776
TI  - Relationship between blood pressure and blood viscosity.

PMID- 8131777
TI  - Accuracy of cardiac output with the Quantascope.

PMID- 8131778
TI  - The mast cell--a potential link between inflammation and cellular cholesterol
      deposition in atherogenesis.
AB  - Mast cells are present in the arterial intima, the site of atherogenesis. In
      fatty streaks (the initial stage of atherogenesis) some of these cells are
      detected in the close vicinity of cholesterol-loaded macrophage foam cells. To
      ascertain whether mast cells could be involved in the formation of foam cells, a
      model system was developed in which isolated rat serosal mast cells were
      incubated with mouse peritoneal macrophages in a medium enriched with either low
      density lipoproteins (LDL) or high density lipoproteins (HDL3). Stimulation of
      the mast cells was found to induce 50-fold enhancement of LDL uptake by the
      macrophages. When stimulated, mast cells exocytose their secretory granules,
      which lose their membranes in the process. The granules then come in contact with
      the medium, which dissolves their histamine, a fraction of their heparin
      proteoglycans and all their chondroitin sulphate proteoglycans, leaving insoluble
      'granule remnants'. These remnants consist of neutral proteases embedded in a
      heparin proteoglycan matrix. Some of the LDL particles in the incubation medium
      bind to this matrix, become degraded by the matrix-bound proteases, and fuse into
      larger particles on the surfaces of the remnants. These LDL particles are
      ingested by the macrophages as they phagocytose the remnants. Simultaneously, the
      soluble heparin proteoglycans interact with other LDL particles, forming
      insoluble complexes which are also phagocytosed by the macrophages. Cholesterol
      from the phagocytosed LDL particles ultimately becomes esterified in the
      macrophages, with formation of foam cells. In addition, mast cells block the
      removal of cholesterol from the foam cells: the remnant enzymes proteolyse HDL
      particles, so lessening their ability to induce efflux of cholesterol from the
      foam cells. These observations suggest that mast cells play an active role in the
      intracellular deposition of cholesteryl esters that is characteristic of early
      atherosclerotic lesions.

PMID- 8131779
TI  - Interactions between bacterial lipopolysaccharides and serum lipoproteins and
      their possible role in coronary heart disease.
AB  - It has been proposed for several decades that infections may be responsible for
      the accelerated development of atherosclerosis. Numerous studies have shown an
      association between atherosclerosis and both viral and bacterial infections. In
      this review, we summarize the evidence linking infections with abnormalities in
      lipid and lipoprotein levels and the role of cytokines in mediating these
      abnormalities. We have also summarized the effects of the interaction between LDL
      and lipopolysaccharides (LPS) on lipoprotein metabolism and their possible
      contributing role to the development of atherosclerosis; the possible role of LPS
      in inducing endothelial cell damage and in stimulating the oxidative metabolism
      of monocytes, leading to the release of superoxide anion (O2-) and to the
      oxidation of LDL. Oxidatively modified LDL has, in recent years, been implicated
      as a contributing factor in the development of atherosclerosis, due to its
      ability to induce the transformation of macrophages into foam cells, to promote
      monocyte binding to the endothelium and to act as a potent chemo-attractant for
      circulating human monocytes. Furthermore, oxidized-LDL is immunogenic and thus,
      it can induce the production of antibodies and subsequent formation of immune
      complexes. These immune complexes, when taken up by macrophages through the Fc
      receptor, induce a marked accumulation of cholesteryl esters in these cells and
      also promote their activation and the subsequent release of cytokines, such as
      interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF alpha). In addition to
      the effects that IL-1 and TNF alpha seem to have on lipid and lipoprotein levels,
      they induce adherence of leukocytes to endothelial cells by promoting the
      expression of several specific cell adhesion molecules; they can also elicit
      synthesis and cell surface expression of procoagulant activity in endothelial
      cells and cause an increase in vascular permeability.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8131780
TI  - Infection and inflammation as risk factors for myocardial infarction.
AB  - Recent studies have illustrated that in addition to the well known risk factors,
      such as lipoproteins, smoking, hypertension, there are others that cause
      atherosclerosis and myocardial infarction. Our knowledge of atherosclerotic
      lesions has increased. We now know that atherosclerotic changes are due to
      inflammatory cell infiltration as well as to increases in migration of vascular
      smooth muscle cells. Endothelial cells play a major role in the pathology of
      vascular changes. In recent years a new risk factor for coronary artery disease
      has been discovered: chlamydia pneumonial infections. Herpes class viruses have
      also been associated with pathology of atherosclerotic lesions. Studies show that
      dental status and bacterial infections are also related to the risk of myocardial
      infarction. This review discusses the possible mechanisms of infection and
      inflammation and whether they are major or modifying risk factors for
      atherosclerosis and myocardial infarction.

PMID- 8131781
TI  - The protective effect of serum lipoproteins against bacterial lipopolysaccharide.
AB  - Lipoproteins bind and inactivate bacterial endotoxin, both in vitro and in vivo.
      Both cholesterol ester-rich and TG-rich lipoproteins, and TG-rich lipid emulsions
      can prevent death in mice when pre-incubated with a lethal dose of endotoxin
      before intraperitoneal administration. Chylomicrons can also prevent death when
      given intravenously after endotoxin in rats. The metabolic fate of lipoprotein
      bound endotoxin appears to be directed by the lipoprotein particle. When
      administered with chylomicrons, the plasma clearance and hepatic uptake of
      endotoxin are enhanced. Endotoxin is shunted preferentially to hepatocytes and
      away from hepatic macrophages, thereby increasing endotoxin excretion [corrected]
      in bile. The survival benefit and alterations in metabolism afforded by
      chylomicrons correlate with a reduction in peak serum levels of tumour necrosis
      factor (TNF), providing a possible mechanism by which lipoproteins protect
      against endotoxin-induced death. These findings suggest a possible role for
      lipoproteins or lipid emulsions in the body's defence against endotoxaemia.

PMID- 8131782
TI  - Infection as a risk factor for cerebral infarction.
AB  - Cerebral infarction is a common complication in severe bacteraemic infections,
      such as endocarditis and meningitis, but it also occurs in other more common,
      milder infections. Febrile infections, mostly of the respiratory tract, and of
      probable bacterial origin, have been found as a risk factor for cerebral
      infarction. There are many mechanisms that could link a preceding infection to
      cerebral infarction, including septic emboli, arteritis, activation of the
      coagulation system and changes in blood rheology.

PMID- 8131783
TI  - Atherogenesis and inflammation.
AB  - Following endothelial injury, monocytes attach to the subendothelium and
      penetrate into the vessel wall, forming macrophage/foam cells by accumulating
      lipids. Macrophages release various products such as interleukins, complement
      factor fragments, tumour necrosis factors, oxidized cholesterol, and oxygen free
      radicals, leading to further endothelial injury and cytolysis. Platelets at the
      site of vascular injury, monocytes, endothelial cells, and smooth muscle cells
      release mitogenic factors which stimulate smooth muscle cell proliferation and
      migration. This smooth muscle cell proliferation, together with organization of
      thrombus and extracellular matrix synthesis, leads to the development of
      atheromatous plaques. Macrophages, by releasing proteases such as collagenase and
      elastase, form an abscess in the plaque which is covered by a thin fibrous cap.
      When this cap ruptures, a local thrombus is formed and depending upon the degree
      and duration of thrombus, and the degree of collateral development the fate of
      this thrombotic process is determined.

PMID- 8131784
TI  - Thrombo-embolic complications in bacteraemic infections.
AB  - Thrombo-embolic complications including stroke and myocardial infarction are
      common in bacteraemic patients with and without endocarditis: about 20% of
      patients with infective endocarditis will develop stroke during their disease.
      Small miliary type myocardial infarctions are found in about 80-90% of autopsied
      endocarditis patients, but large myocardial infarctions are much more infrequent
      and acute myocardial infarctions are seldom diagnosed in the lifetime of these
      patients. About 10% of bacteraemic patients without endocarditis will develop
      stroke within one month of the onset of bacteraemia, and about 4% of bacteraemic
      patients will develop myocardial infarction. The risk of cerebral or myocardial
      infarction is very high in bacteraemic patients compared with the corresponding
      risk in the general population of the same age, and it has been estimated that
      about 10% of all strokes are associated with bacteraemic infections. The
      mechanisms which could cause thrombo-embolic complications in septic patients are
      numerous, but activation of the coagulation system is probably the most
      important. Currently, appropriate antimicrobial therapy is the best way to reduce
      mortality and also probably thrombo-embolic complications in bacteraemic patients
      who are not routinely using any anticoagulant therapy.

PMID- 8131785
TI  - Cytomegalovirus and atherosclerosis.
AB  - An avian herpesvirus is known to cause atherosclerosis in chickens. The same
      virus can induce a proliferative disease, malignant lymphoma, suggesting that
      this agent may also have transforming potential and thus stimulate the
      proliferation of arterial smooth muscle cells, a prominent feature of
      atherogenesis. The evidence for involvement of cytomegalovirus (CMV), a member of
      the human herpesvirus family, in atherosclerosis is much more circumstantial. The
      finding of CMV antigen and nucleic acid sequences in arterial smooth muscle cells
      of humans suggests that viral infection of the arterial wall may be common in the
      general population, including patients with severe atherosclerosis. In
      seroepidemiological studies, high levels of CMV antibodies were found to be
      associated with clinically manifest atherosclerotic disease, suggesting that a
      periodically activated latent infection or a continuously active infection is
      present in patients with atherosclerosis. Since the viral genome but not
      infectious virus is found in arterial cells, the artery itself may be the site of
      CMV latency. Of particular significance is the recent finding that heart
      transplant recipients, who are immunosuppressed, and who are also actively
      infected with CMV, are prone to develop accelerated atherosclerosis in the
      transplanted organ. Although suggestive, these observations by themselves do not
      demonstrate that viruses have a role in the pathogenesis of atherosclerosis, but
      they support a working hypothesis of the steps involved.

PMID- 8131786
TI  - Herpes simplex virus and atherosclerosis.
AB  - This paper presents a brief overview of our current understanding of the
      relationship between herpes simplex virus (HSV) and atherogenesis. In the search
      for a viral trigger of atherosclerosis, several investigators reported the
      detection of herpes simplex virus in some, but not all atherosclerotic lesions.
      HSV infections are very common, not only in atherosclerotic patients but also in
      the general population, making epidemiological studies difficult to interpret.
      Different mechanisms by which HSV may contribute to atherogenesis have been
      described. In vascular cells, HSV infection leads to lipid accumulation. HSV
      infection of endothelial cells attracts leukocytes with subsequent inflammatory
      damage; it activates procoagulant changes on endothelium with increased thrombin
      generation and platelet adhesion, and changes its interaction with extracellular
      matrix proteins. Future studies should delineate whether these mechanisms are
      operative in the pathogenesis of atherosclerosis.

PMID- 8131788
TI  - Dental infections as a risk factor for acute myocardial infarction.
AB  - The so-called classic risk factors of coronary heart disease (CHD) do not explain
      all its clinical and epidemiological features. Recent evidence suggests that
      certain infections, among them dental infections, are involved in the
      pathogenesis of CHD. Case-control studies have revealed an association between
      dental infections and acute myocardial infarction and chronic coronary heart
      disease. A large epidemiological survey revealed an association between missing
      teeth and CHD and a recent 14-year follow-up of 9760 individuals showed that
      periodontitis is associated with an increased risk of coronary heart disease.
      Preliminary results suggest that the severity of dental infections correlates
      with the extent of coronary atheromatosis. Individuals with severe dental
      infections also have higher level of von Willebrand factor antigen, leukocytes
      and fibrinogen. Streptococcus sanguis has been shown to aggregate human platelets
      in vitro. The mechanism behind the association between dental infections and CHD
      could be the effect of bacteria on the cells taking part in the pathogenesis of
      atherosclerosis and arterial thrombosis.

PMID- 8131787
TI  - Bacteriology of dental infections.
AB  - The most common dental diseases, periodontal disease and dental caries, are
      chronic infections caused by bacteria of normal oral flora. When these bacteria
      increase in number and irritation exceeds the host defence threshold, disease
      arises. The human oral flora comprises more than 300 different bacteria. During
      the last decade approximately 10 species, mainly Gram-negative anaerobes, have
      been noted as putative pathogens in periodontal disease. The Gram-positive and
      facultatively anaerobic mutans streptococci are aetiologically the most important
      bacteria in dental caries. Data have rapidly increased on the association of
      these bacteria with certain periodontal diseases or caries, on phenotypic and
      genotypic characteristics, pathogenic mechanisms, antibiotic susceptibility
      patterns and transmission among family members. Chronic dental infections have
      been the focus of renewed interest because of recent advances in oral
      microbiology as well as in medicine. We now know that in addition to oral
      streptococci, recently classified, fastidious periodontal anaerobes can be
      detected from various extra-oral infections. Oral bacteria may spread into the
      blood stream through ulcerated epithelium in diseased periodontal pockets and
      cause transient bacteraemias, which are regarded as increased risk, especially
      for immunocompromised patients or persons with endoprotheses. In these patients,
      routine antibiotic prophylaxis is recommended for invasive dental care
      procedures. Also the new association between dental infections and
      myocardial/cerebral infarction have offered new challenges for cooperation
      between dental and medical researchers.

PMID- 8131789
TI  - Missing teeth and ischaemic heart disease in men aged 45-64 years.
AB  - The aim of the present study was to investigate the associations between number
      of missing teeth (expressing sustained oral infections) and diagnosed ischaemic
      heart disease using cross-sectional data from 1384 men aged 45-64 years. The
      study population was derived from a representative sample of adult Finns.
      Ischaemic heart disease was considered to be present in those with angina
      pectoris or previous myocardial infarction, whether definite or possible. A tooth
      was recorded as missing if none of it was visible or could be felt with an
      instrument. According to multiple linear analyses, the variation in ischaemic
      heart disease was independently explained by age, clinical diagnosis of arterial
      hypertension, geographical area, educational level and number of missing teeth.
      Smoking and cholesterol were not significant explanatory factors. The explanation
      for the observed association between missing teeth and ischaemic heart disease is
      that they may share a common behavioural background factor. There may also be a
      more direct causal relationship between the phenomena.

PMID- 8131790
TI  - Pathogenetic mechanisms and epidemiology of Chlamydia pneumoniae.
AB  - The antibody prevalence data indicate that C. pneumoniae infections are common
      worldwide and more frequently occur in middle-aged and elderly males than in
      females. C. pneumoniae infections are first acquired in childhood in heavily
      populated areas, whereas in northern countries, first infections are generally at
      teenage and in Scandinavia, typically at the time of military service. All
      chlamydial species tend to cause chronic infections, with severe sequelae
      developing 10 to 50 years after the primary infections. If C. pneumoniae resides
      in alveolar macrophages or in vascular endothelial cells in chronic infections
      the bacteria and their structural components, such as lipopolysaccharides have an
      easy access to circulation. The continuous induction of cytokines by C.
      pneumoniae may lead to chronic inflammation of vascular endothelium.

PMID- 8131791
TI  - Chlamydia pneumoniae infection as a risk factor in acute myocardial infarction.
AB  - While early observations on the possible connection between chlamydia and
      arteriosclerosis remain unnoticed, it was found recently that in acute myocardial
      infarction (AMI) a sero response to an epitope of chlamydial lipopolysaccharide
      (LPS) could be demonstrated in about 70% of cases. Moreover, steadily elevated
      titres against Chlamydia pneumoniae in patient sera pointed to a possibility that
      chronic infection due to the agent was exacerbated in AMI. This assumption has
      been further supported by the finding of (a) elevated C. pneumoniae antibody
      titres in coronary heart disease patients in several studies, (b) the presence of
      immune complexes containing chlamydial LPS in acute AMI cases and their formation
      of antigen excess followed a month later by antibody excess, (c) the presence of
      antibodies to C. pneumoniae proteins in immune complexes in chronic coronary
      heart disease. The presence of elevated antibody titres and/or immune complexes
      containing chlamydial LPS was a significant independent risk factor (up to 2.6,
      CL, 1.3 to 5.2) for AMI 3-6 months before cardiac incidents in the Helsinki Heart
      Study. The odds ratio was especially significant (up to 7.2, CL, 1.4 to 35) if
      the cohort on cholesterol-lowering drug was followed.

PMID- 8131792
TI  - Chlamydia pneumoniae, strain TWAR and atherosclerosis.
AB  - Infection with Chlamydia pneumoniae, strain TWAR, has been associated with
      atherosclerotic cardiovascular disease in two types of investigations,
      seroepidemiological and morphological-molecular. A series of seroepidemiological
      studies from Finland and the United States have shown a statistically significant
      association between several types of TWAR antibody, including immune complexes,
      and atherosclerotic disease of the coronary and carotid arteries. The
      morphological-molecular studies have shown the C. pneumoniae organism in atheroma
      of the coronary arteries, and aorta but not in normal arteries. The presence of
      the organism in atheroma has been demonstrated by electron-microscopy,
      immunocytochemical staining with TWAR-specific monoclonal antibody and by the
      polymerase chain reaction for TWAR-specific DNA. The aetiological or pathogenic
      significance of the association of C. pneumoniae and atherosclerotic disease
      remains to be determined.

PMID- 8131793
TI  - Altered serum lipid profile after systemic infection in children: risk factor for
      CHD?
AB  - Systemic infections may thicken the intima of coronary arteries and modify the
      serum lipid profile. Infants and children are particularly susceptible to such
      intimal thickening, the signs of which are more pronounced in infants who have
      evidence of infection at death. The topography of the thickenings, their greater
      size in males, and in families with a history of coronary heart disease favours
      the idea that the thickenings are pre-atherosclerotic. Infections modify the
      serum lipid pattern: serum high density lipoprotein (HDL) cholesterol
      concentration decreases and stays low during convalescence. Thus repeated
      infections might prove to be a risk factor for atherosclerosis via their effect
      on HDL concentration.

PMID- 8131794
TI  - IL-1 inducible genes in human umbilical vein endothelial cells.
AB  - In an attempt to understand more directly the molecular mechanisms involved in
      the cellular response of endothelial cells to Interleukin-1 (IL-1), we have made
      several cDNA libraries from human umbilical vein endothelial cells (HUVEC)
      stimulated for 1 h with IL-1 in the presence of cycloheximide. The cDNA libraries
      were differentially screened with labelled cDNA derived from mRNA isolated from
      untreated or IL-1 treated HUVEC. Forty cDNA clones induced by IL-1 were isolated
      and partially sequenced. Thirty-eight of these corresponded to known genes, that
      is IL-8, ELAM-1, GRO-alpha, GRO-beta, PA-I and I-kB. The last two clones
      contained an identical insert belonging to a previously unknown gene. The full
      length cDNA of this new gene was isolated and called PTX3. It encodes for a 42
      kD, 381 amino-acid long protein which shows in its 3' half a high degree of
      homology to all the known members of the pentaxin gene family, including C
      reactive protein (CRP) and serum amyloid P component (SAP). PTX3 may represent a
      novel marker of inflammatory reactions, particularly those involving the vessel
      wall.

PMID- 8131795
TI  - Fibrinogen as a cardiovascular risk factor--interrelationship with infections and
      inflammation.
AB  - Epidemiological evidence suggests that fibrinogen represents a major
      cardiovascular risk factor. Clinical data is in full agreement with this
      hypothesis. As fibrinogen also represents an acute phase protein, its association
      with atherosclerosis could be linked to infection or inflammation of other
      organs. Moreover, it could be connected to the inflammatory phenomena of
      atherosclerosis itself. These two possible explanations for the link between
      fibrinogen and atherosclerosis are discussed in detail. On balance, the evidence
      for either is not fully convincing. Therefore the most likely explanation for the
      striking association between fibrinogen and cardiovascular events is that
      hyperfibrinogenaemia is causally related to atherothrombosis, independent of its
      role as an acute phase protein. Several plausible pathophysiological pathways
      exist which would explain how fibrinogen leads to major cardiovascular disease.
      It is concluded that fibrinogen is a cardiovascular risk factor in its own right;
      its measurement should be included in future cardiovascular risk profiles.

PMID- 8131796
TI  - Cellular activation by thromboxane A2 and other eicosanoids.
AB  - Thromboxane A2 (TXA2), the major cyclooxygenase (COX) product of arachidonic acid
      (AA), activates platelets and is a potent vasoconstrictor. The functional
      importance of this eicosanoid has been demonstrated in syndromes of acute
      coronary ischaemia. The cellular response to this agonist is tightly regulated.
      The liberation of AA from membrane phospholipids is conventionally thought to be
      the rate limiting step in TXA2 biosynthesis. However, the discovery of a second,
      highly regulated COX gene (COX-2) and the demonstration of product-based
      inactivation of COX and thromboxane synthase suggest a more complex regulation of
      TXA2 formation. TXA2 signalling is mediated by a G-protein linked receptor
      (PGH2/TXA2 receptor) which activates phospholipase C (PLC). Pharmacological
      studies suggest two distinct binding sites on platelets, but receptor
      heterogeneity has yet to be documented at a molecular level. The PGH2/TXA2
      receptors are linked via a pertussis and cholera toxin-insensitive G-protein
      which has not been fully characterized, but is thought to belong to the Gq class
      of G-proteins. The diversity of G-protein alpha subunits, and growing evidence
      suggesting functional roles for the beta-gamma subunit, support a possible dual
      signalling mechanism of cellular activation. This may be of particular importance
      in regulating the response to eicosanoids with contrasting actions. A receptor
      for prostacyclin (PGI2) has not yet been cloned but biochemical studies suggest
      that it is linked to the activation of adenylate cyclase via Gs. At least three
      distinct prostaglandin E receptors have been identified. Desensitization of the
      cellular responses to the activation of TXA2, PGI2 and PGE receptors have been
      demonstrated and potential phosphorylation sites in their COOH terminal ends may
      be important in mediating this effect.

PMID- 8131797
TI  - Inflammation in atheroma: implications for plaque rupture and platelet-collagen
      interaction.
AB  - Atherosclerosis is an inflammatory reaction to accumulated extracellular lipid in
      the arterial intima. Evidence from pathological studies indicate that there is
      constant deposition and lysis of fibrin within the atherosclerotic arterial wall.
      In patients with stable peripheral atherosclerosis, the functional severity of
      the disease is associated with circulating fibrinogen and degradation of cross
      linked fibrin reflecting procoagulant activity in the blood-vessel wall
      interface, or in the wall itself. In atheromas the fibrinolytic activity is
      connected to macrophages, which can assemble in the plasminogen-plasmin system
      and generate plasmin-mediated pericellular proteolysis in tissues with
      inflammation. Plasmin capable of activating collagenase may therefore be a
      candidate for plaque rupture. The nature of the exposed vascular tissue, the
      inflammatory state, tissue-factor dependent thrombin generation and the degree of
      matrix degradation regulate platelet reactivity. Little is yet known about
      platelet adhesive functions in proteolyzed collagens that are the underlying
      substrate where platelets deposit during plaque rupture, the triggering event for
      thrombosis. Research in these areas is likely to improve the understanding of the
      thrombogenicity of atheromas when the tissue is suddenly exposed to blood.

PMID- 8131798
TI  - Tissue factor and the extrinsic pathway of coagulation during infection and
      vascular inflammation.
AB  - Tissue factor is a potent initiator of blood coagulation. In tissue sections, it
      has been immunologically demonstrated in cells normally not in contact with
      circulating blood, and elevated activity has been repeatedly demonstrated in
      peripheral blood monocytes of patients considered to be at risk for thrombosis.
      Studies with endothelial cells and monocytes in culture have documented the
      induction of tissue factor synthesis by biochemical mediators of the inflammatory
      process. Lytic processes, such as those caused by complement activation or viral
      infections, increase the tissue factor activity several fold over the basal level
      of the affected cells. Diminished anti-thrombotic properties of endothelium, and
      induced tissue factor expression in endothelium and monocytes/macrophages,
      combined with the increased specific procoagulant activity resulting from cell
      membrane damage, may endow inflammatory foci with dramatically elevated
      procoagulant activity. Levels of tissue factor activity at which procoagulant
      mechanisms escape regulation by natural anticoagulant mechanisms and produce
      thrombosis remain to be determined.

PMID- 8131799
TI  - Recurrent wheezing in children with respiratory syncytial virus (RSV)
      bronchiolitis in Qatar.
AB  - Records of 70 infants admitted to Hamad General Hospital with RSV bronchiolitis
      and a similar number of controls were retrospectively reviewed. Two years after
      admission, 44% of the infants with RSV bronchiolitis developed recurrent wheezing
      compared with only 12.9% of controls (P = 0.001). A family history of atopy
      appeared not to be a significant predisposing factor for the occurrence of
      recurrent wheezing in post RSV bronchiolitis patients. These results are similar
      to those from similar studies in industrialized countries.

PMID- 8131800
TI  - Neonatal suppurative parotitis: a vanishing disease?
AB  - A case of neonatal suppurative parotitis due to Klebsiella pneumoniae is
      described. This is the first case reported in the last 20 years. Infection with
      unusual microorganisms should be taken into account when planning antibiotic
      treatment, especially in hospital acquired infections of the salivary glands in
      the newborn.

PMID- 8131801
TI  - Cystic fibrosis: the delta F508 mutation does not lead to an exceptionally severe
      phenotype. A cohort study.
AB  - In an attempt to ascertain a relationship between genotype and phenotype, we
      studied the pulmonary and nutritional status of 123 cystic fibrosis patients with
      known genotype at an age of 8.5-10 years. Patients represent a cohort as they are
      almost all those born and diagnosed in a given area and period. They were
      followed at a single centre using uniform diagnostic and treatment protocols.
      Pulmonary and nutritional status of homozygous delta 508 patients did not differ
      from that of compound heterozygotes or of patients with other unspecified
      genotypes. Pulmonary manifestations varied widely in all genotype groups. With
      the given number of patients, a slightly higher mortality of delta F508
      homozygotes could have been coincidental. We conclude that up to the age of 8.5
      10 years the severity of pulmonary lesions and nutritional deficiencies is not
      related to the delta F508 mutation.

PMID- 8131802
TI  - White matter abnormalities in patients with treated hyperphenylalaninaemia:
      magnetic resonance relaxometry and proton spectroscopy findings.
AB  - In order to further clarify the pathogenesis and clinical significance of MRI
      white matter abnormalities in treated hyperphenylalaninaemia (HPA), ten patients
      (seven type I HPA, two type II and one type III) underwent T2 relaxometry (n = 8)
      and/or 1H spectroscopy (n = 7) in addition to conventional MR spin-echo imaging
      at 1.5 T. Two patients with severe MRI abnormalities had repeat examinations
      during and after a 6- to 8-month period of strict diet control. The clinical
      evaluation included a detailed neurological examination. In nine out of ten
      patients visual evoked potentials (VEP) were obtained parallel to the MR
      examination. MR imaging demonstrated typical symmetrical areas of prolonged T2
      relaxation time predominantly in the posterior periventricular white matter in
      all but one of type I and II patients. There was no consistent relationship
      between MRI findings and time of diagnosis/initiation of therapy, IQ or visual
      evoked potential changes. MRI abnormalities tended to be more severe in patients
      with poor dietary control and high current plasma phenylalanine levels, whereas a
      normal MRI was found only in patients with plasma phenylalanine levels
      continuously below 0.36 mmol/l. There was marked regression of MRI abnormalities
      already after 3 months of strict diet control. T2 relaxometry showed a bi
      exponential behaviour of T2 in the affected white matter, with a slow component
      of about 200-450 ms, indicating an increase in free (extracellular) water. 1H
      spectroscopy revealed no signs of severe neuronal damage. We conclude, that the
      observed white matter changes in treated HPA probably represent reversible
      structural myelin changes rather than permanent demyelination.

PMID- 8131803
TI  - Contribution of odd-numbered fatty acid oxidation to propionate production in
      neonates with methylmalonic and propionic acidaemias.
AB  - Newborns with disturbed propionate metabolism (propionic and methylmalonic
      acidaemias) accumulate during fetal life large amounts of odd-numbered long-chain
      fatty acids in adipose tissue (8% to 10% of total fatty acids vs 1% in normal
      controls) and other body lipids. During periods of acute catabolism, such as in
      the early days of life, mobilization and oxidation of odd-chain fatty acids from
      adipose tissue yield extensive amounts of toxic propionyl-CoA in the mitochondria
      and thus might contribute to the severe illness of the patients. Our data suggest
      that not only catabolism of protein but also that of adipose tissue has to be
      avoided in order to alleviate the neonatal illness of patients with propionic and
      methylmalonic acidaemias. It seems prudent to avoid prolonged fasting during the
      1st year of life.

PMID- 8131804
TI  - Correlations between radiological and cytological findings in early development
      of bronchopulmonary dysplasia.
AB  - Sequential chest radiographs from 40 newborn infants requiring assisted
      ventilation for respiratory distress syndrome or other conditions were evaluated
      with a new scoring system aiming at identifying abnormal expansion patterns and
      interstitial infiltrates representing an early stage of bronchopulmonary
      dysplasia (BPD). Age at examination ranged from 3 to 23 days. Tracheal effluent
      samples obtained from the babies during the same period of observation were
      examined cytologically for evidence of regenerating airway epithelium with
      squamous metaplasia, indicating BPD. According to the radiological scoring system
      24 babies (60%) developed BPD, first diagnosed at a median age of 9 days. By
      cytological criteria 20 babies (50%) developed BPD, first diagnosed at a median
      age of 10.5 days. The results from radiological and cytological diagnosis of BPD
      were concordant in 16 babies (P < 0.05 by chi-square test). Using oxygen
      dependency at the age of 28 days as evidence of established BPD, the radiological
      scoring system alone had a sensitivity of 93% and a specificity of 53%. The
      corresponding figures for cytological assessment alone were 73% and 58%,
      respectively. By combining radiological and cytological findings, values for
      sensitivity and specificity were 67% and 68%, respectively.

PMID- 8131805
TI  - Results of parenchymal and angiographic magnetic resonance imaging and
      neuropsychological testing of children after stroke as neonates.
AB  - We describe the long-term follow up of infants after neonatal stroke of the
      middle cerebral artery (MCA). Stroke was diagnosed by CT scan in eight full-term
      neonates. Three dimensional (volume) magnetic resonance angiography (MRA) is a
      noninvasive technique that images the arterial vessels without contrast agents.
      All patients, aged from 1.5 to 8.4 years, were investigated by MRI and MRA and by
      neuropsychological tests. Cognitive development was investigated by intelligence
      tests, tests of visual perception, motor and language development. Out of the
      eight patients, seven had a retarded mental and motor development, and 50% of the
      children were treated for epilepsy. Seven patients had a spastic hemiparesis.
      Seven out of eight children showed major cognitive deficits. In all patients, MRI
      revealed clear parenchymal defects with variable distribution patterns. MRA
      studies showed abnormalities corresponding to the expected vascular distribution.
      Children with complications at delivery, with seizures, and an interruption of
      the main stem of MCA as demonstrated on MRA had the least favourable long-term
      follow up prognosis with severe cognitive delays.

PMID- 8131806
TI  - Protein quality of human milk fortifier in low birth weight infants: effects on
      growth and plasma amino acid profiles.
AB  - Serum preprandial essential amino acid, urea and prealbumin concentrations, and
      growth rates were studied in appropriate for gestational age low birth weight
      infants fed one of three regimens: (1) human milk enriched with human milk
      protein (n = 17); (2) bovine whey protein hydrolysate (n = 18; and (3) a mixture
      of bovine proteins, peptides and amino acids designed to have an amino acid
      composition close to that of human milk proteins (n = 18). Energy and nitrogen
      intakes were similar in all groups. Growth rates and gross metabolic responses
      did not differ between the feeding groups. There were also no differences in the
      amino acid profiles between those infants fed human milk protein fortifier and
      mixed bovine protein fortifier. Infants fed the whey fortifier had significantly
      higher threonine concentrations in comparison to those fed exclusively human milk
      protein (287 +/- 63 mumol/l vs 168 +/- 26 mumol/l) whereas the levels of some
      other essential amino acids (i.e. valine, leucine, lysine, histidine,
      phenylalanine and tryptophan) were lower. The results indicate that growth rates
      and gross metabolic indices do not depend on the protein quality of human milk
      fortifiers. However, the addition of well balanced mixtures of bovine proteins to
      human milk results in amino acid profiles similar to those observed in LBW
      infants fed similar amounts of human milk proteins.

PMID- 8131807
TI  - Carbamazepine hypersensitivity and rickettsiosis mimicking Kawasaki disease.
AB  - We report on two patients whose clinical presentation resembled that of Kawasaki
      disease. The first patient was a boy with epilepsy, whose symptoms first appeared
      following treatment with carbamazepine. The second boy had Mediterranean Spotted
      Fever. The significance of medical history in avoiding overdiagnosis of Kawasaki
      disease is emphasized.

PMID- 8131808
TI  - Trends in hospitalization among asthmatic children in Finland from 1972 to 1986.
AB  - Trends in hospitalization among asthmatic children were examined over a period of
      15 years on the basis of a hospital discharge register covering all hospitals in
      Finland. The annual mean population under 15 years of age, 992,994, had a total
      of 37,965 hospitalization periods on account of asthma during the interval
      studied. Examination in 5 year age groups showed treatment periods for boys under
      5 years to have increased by 1.8% annually relative to the total population (95%
      confidence interval +0.6(-)+3.1) and those for girls by 22% (95% CI +0.7(-)+3.7),
      whereas the changes in the older age groups were insignificant. First admissions
      decreased annually in all age groups in the case of both boys and girls. The
      numbers of hospitalization periods due to asthma were significantly higher for
      boys than for girls. The use of hospital services by asthmatic children was
      appropriate during the period concerned, which may partly be explained by the
      fact that child health care is well organized in Finland and the treatment of
      childhood asthma entirely in the hands of paediatricians.

PMID- 8131809
TI  - Neuro-ophthalmological manifestations of tick-borne borreliosis: a case report.

PMID- 8131810
TI  - Bloody nipple discharge in a 3-year-old girl.

PMID- 8131811
TI  - Facilitation of hyperphenylalaninaemia phenotype assessment by genotype analysis.

PMID- 8131812
TI  - L. Emmet Holt, Jr. (1895-1974).

PMID- 8131813
TI  - Guidelines for neonatal screening programmes for congenital hypothyroidism.
      Working group on congenital hypothyroidism of the European Society for Paediatric
      Endocrinology.

PMID- 8131814
TI  - The control of the ductus venosus: an update.

PMID- 8131815
TI  - Extended deep vein and inferior vena cava thrombosis in a 15-year-old boy:
      successful lysis with recombinant tissue-type plasminogen activator 2 weeks after
      onset of symptoms.
AB  - We present the case of a 15-year-old boy with thrombosis of the inferior vena
      cava, the femoral, inguinal, and renal veins of unknown origin. Although the
      thrombosis was 2 weeks old, thrombolytic therapy with recombinant tissue-type
      plasminogen activator (maximum dosage: 0.4 mg/kg/h) was started as this appeared
      to be the only change to re-establish normal kidney function. After 1 week,
      treatment was discontinued because of generalized bleeding. At this time, the
      infrarenal inferior vena cava was again patent with complete lysis of all other
      clots. Phlebography 3 months after lysis documented an abnormal renal vein, a
      tubular, subhepatical stenosis of the inferior vena cava and a large collateral
      vessel between the inferior vena cava and the azygos vein.

PMID- 8131816
TI  - Liposomal amphotericin-B (AmBisome) for treatment of cutaneous widespread
      candidosis in an infant with methylmalonic acidaemia.
AB  - In a 10-week-old infant with vitamin B12-unresponsive methylmalonic acidaemia,
      cutaneous candidosis (Candida albicans) progressed rapidly despite topical
      antifungal treatment. After 1 week of intravenous therapy with liposomal
      amphotericin-B (AmBisome) the dermatitis disappeared completely and blood
      cultures were sterile. No side-effects were observed. This is one of the first
      experiences in the treatment of infants with this new antifungal agent.

PMID- 8131817
TI  - Circulating immunoreactive growth hormone releasing hormone concentrations and
      growth hormone response to growth hormone releasing hormone in short children.
AB  - To study the role of peripheral immunoreactive growth hormone releasing hormone
      (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone
      (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range
      1.6-16.3 years) and a mean relative height score of -3.2 SD (range -5.0-2.1 SD)
      were investigated. The children were divided into prepubertal (n = 35) and
      pubertal (n = 11) and the prepubertal children further into three groups based on
      their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine:
      (1) GH deficient subjects (maximal GH < 10 micrograms/l in both tests); (2)
      discordant responders (maximal GH < 10 micrograms/l in one test and > or = 10
      micrograms/l in the other); and (3) normal responders (maximal GH > or = 10
      micrograms/l in both tests). Peripheral ir-GHRH concentrations were measured
      during the IIH test by radioimmunoassay after purification of plasma samples on
      Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into
      group 2 and 9 into group 3. Children in group 1 were older than those in group 3.
      There were no significant differences in relative heights and weights or absolute
      and relative growth velocities between the groups. Subjects in groups 1 and 2 had
      lower maximal GH responses to GHRH than those in group 3. There were no
      significant differences in the basal plasma ir-GHRH concentrations between the
      groups. Nine children (19.6%) had somatotrophs with a poor response to a single
      dose of exogenous GHRH (maximal GH < 10 micrograms/l).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8131818
TI  - Hypergalactosaemia in a patient with portal-hepatic venous and hepatic arterio
      venous shunts detected by neonatal screening.
AB  - Hypergalactosaemia was discovered in a newborn girl during routine metabolic
      screening. Hereditary enzyme deficiency was ruled out. She had multiple hepatic
      haemangiomas with portal-hepatic venous and hepatic arterio-venous shunts. Since
      she showed signs of high-output heart failure due to the arterio-venous shunt,
      hepatic artery embolization was performed at age 3 months. A galactose tolerance
      test was performed before and after embolization and when the haemangioma no
      longer appeared on ultrasonography. Even after embolization, the level of blood
      galactose was abnormally elevated in the galactose tolerance test, but the blood
      galactose was eliminated more rapidly than before embolization. When the hepatic
      haemangioma was no longer detected by ultrasonography, the peak galactose level
      decreased. We surmise that the hypergalactosaemia was due to these shunts. In
      cases of hypergalactosaemia of unknown cause; liver haemangioma with portal
      hepatic venous shunting should be considered as a possible cause. If a hepatic
      arterio-venous shunt also exists, this may contribute to the effect of the
      portosystemic shunting.

PMID- 8131819
TI  - Pubertal development in thalassaemic patients after allogenic bone marrow
      transplantation.
AB  - To obtain further insight into gonadal function, a series of 50 prepubertal
      patients with beta-thalassaemia major (24 boys and 26 girls) aged from 12.6 to 18
      years (mean 15 years) who had received a bone marrow transplantation (BMT) during
      childhood or the peripubertal period, at the age of 3.6-14.5 years (mean 10.8
      years), were periodically re-evaluated at intervals of 6-12 months. The last
      evaluation was done 1-9 years (mean 4.2 years) after BMT. At each examination we
      measured height, pubertal stage, plasma gonadotrophins (LH and FSH) before and
      after the GnRH stimulation test (i.v.), sex steroids (total and free testosterone
      in males, and 17 beta-oestradiol in females), serum ferritin and bone age. Fourty
      percent of patients entered or passed through puberty normally despite clinical
      and hormonal evidence of gonadal dysfunction in most of them. A correlation was
      not found between the pubertal stage and age at BMT, and no statistical
      difference between patients who did not enter into puberty and patients with
      spontaneous pubertal development was found in serum ferritin levels. Our data
      confirm that gonads in male and female thalassaemic patients are exposed to the
      cytotoxic effects of the preparative transplant regime with alkylating agents. In
      some patients absence of pubertal development was due to gonadotrophin
      insufficiency, probably secondary to previous iron overload. These findings
      emphasize the need for a vigilant long-term follow up study of thalassaemic
      patients who have had BMT.

PMID- 8131820
TI  - Effect of interleukin 2 on intractable herpes virus infection and chronic
      eczematoid dermatitis in a patient with Wiskott-Aldrich syndrome.
AB  - Recombinant interleukin 2 (rIL2) was administered to a patient with Wiskott
      Aldrich syndrome for the treatment of an intractable facial herpetiform lesion.
      This treatment appeared to be effective in suppressing the virus activity. At the
      same time, a transient improvement of the chronic eczematoid dermatitis was
      observed. During rIL2 administration, the CD3+ and CD4+ subsets of peripheral
      blood lymphocytes increased in number. These changes might play an important role
      in the induction of anti-viral immunity and in the improvement of dermatitis.

PMID- 8131821
TI  - GABA-like immunoreactive innervation and dendro-dendritic contacts in the
      ventrolateral dendritic bundle in the cat S1 spinal cord segment: an electron
      microscopic study.
AB  - The motoneurons (MNs) in the ventrolateral nucleus (VLN) of the upper sacral
      spinal cord segments in the cat supply the external sphincters and the
      ischiocavernosii muscles. The dendrites of the MNs in the VLN are arranged into
      rostro-caudally oriented bundles (ventrolateral dendritic bundle, VLB). In this
      study we describe the distribution and synaptic arrangement of gamma-aminobutyric
      acid-immunoreactive (GABA-IR) axonal bouton profiles innervating the VLB. This
      was accomplished using the peroxidase-antiperoxidase technique and a polyclonal
      antibody raised against glutaraldehyde-conjugated GABA. The VLN receives an
      extensive innervation of GABA-IR axonal bouton profiles that surround both cell
      bodies and dendrites. Twenty-five per cent of the total number of vesicle
      containing axonal profiles in the VLN neuropil were estimated to be GABA-IR. On
      cell bodies in the alpha-motoneuron size-range, the membrane covering of GABA-IR
      bouton profiles was about 18% and they constituted about 29% of the total
      membrane covering of axonal bouton profiles. Quantitative analysis of GABA-IR
      bouton profiles on dendrites revealed membrane covering figures rather similar to
      those on the cell bodies. They were not randomly distributed within the dendritic
      arborisations. Instead, they were very infrequent (2.5% of the covering) on small
      calibre dendrites (< 1 microns) as compared to larger dendrites (> 1 microns, 14
      18.5% of the covering), although the total membrane covering of axonal bouton
      profiles was rather similar for all dendrites (42-52%). The data on membrane
      covering by GABA-IR boutons presented here may be low estimates due to technical
      limitations, indicating that the GABAergic input to this region might be even
      more extensive. A frequent finding was that one and the same GABA-IR bouton made
      synaptic contact with two to three adjacent dendrites. This type of synaptic
      arrangement among the VLN MNs indicates a divergence of the GABAergic input at
      the terminal level. In addition, the postsynaptic dendrites involved in such
      arrangements often disclosed dendro-dendritic contacts. In total, 44% of the
      bundled dendrites in the VLN disclosed direct dendro-dendritic contact regions.
      These contacts were most often of the puncta adherentia type, while desmosome
      type contacts were less frequent. None of the dendro-dendritic contacts studies
      had the characteristics of a gap junction. Taken together, the present results
      indicate that GABA may be a transmitter substance in a large fraction of the
      synaptic input to the VLN MNs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8131822
TI  - Organisation of the thalamofugal visual projections in chick embryos, and a sex
      difference in light-stimulated development.
AB  - The organisation of the thalamofugal visual projections to the forebrain has been
      determined in chick embryos by injecting retrograde tracers (true blue and either
      fluorogold or diamidino yellow) into the left or right hyperstriatum. The embryos
      were injected on day 19 of incubation and allowed to survive for a further 4
      days. Unlike chicks posthatching, the embryos were found to have no asymmetry of
      the thalamofugal visual projections, irrespective of whether they had received 24
      h of light exposure prior to injecting the tracer dyes or had been kept in
      darkness. The light exposure did, however, lead to a significant increase in the
      ratio of the number of cell bodies in the thalamus labelled contralaterally to
      the injection site to the number labelled ipsilaterally (CI ratio) in male
      embryos. The elevation of the CI ratio appeared to be due to an increase in the
      number of contralateral projections from each side of the thalamus to the
      hyperstriatum on the other side of the forebrain. Thus, growth of these visual
      projections is promoted by light experience during the later stages of embryonic
      development. Most likely, light stimulation promotes increased arborisation of
      end-terminals in the hyperstriatum. Development of the thalamofugal visual
      projections in female embryos was not influenced by exposure to light, a finding
      consistent with earlier studies demonstrating that circulating oestrogen either
      inhibits or over-rides the sensitivity of these developing neurones to light
      stimulation.

PMID- 8131823
TI  - Identification of time-varying dynamics of the human triceps surae stretch
      reflex. I. Rapid isometric contraction.
AB  - We have examined the time variations of stretch reflex dynamics throughout rapid
      voluntary changes in the isometric contraction level of the human triceps surae
      muscles. This was achieved by superimposing a small stochastic displacement upon
      many such changing contractions and then identifying the time-varying
      relationship between the perturbation and the evoked electromyograms (EMGs). An
      "ensemble" time-varying system identification technique was used to estimate
      these input-output dynamics as a set of impulse response functions, one for each
      time before, during, and after the change in contraction level, with a temporal
      resolution equal to the data acquisition rate. Three main findings resulted.
      First, stretch reflex gain (relating joint velocity to EMG) was significantly
      modulated during changes in voluntary contraction level, increasing as the
      subject contracted the muscles and decreasing as the subject relaxed. Second,
      stretch reflex dynamics did not change with contraction level, even when its gain
      varied substantially. Third, the time course of the gain changes closely followed
      the level of the EMG, even though the subjects used rather different activation
      and deactivation patterns. These results suggest that, for the behavior studied
      (i.e., rapid changes in isometric contraction level), stretch reflex gain and
      motoneuron pool activation level were controlled by a common descending command
      rather than being independently specified.

PMID- 8131824
TI  - Identification of time-varying dynamics of the human triceps surae stretch
      reflex. II. Rapid imposed movement.
AB  - We examined the time-varying dynamics of the human triceps surae stretch reflex
      before, during, and after a large stretch was imposed upon the ankle joint,
      during a constant voluntary contraction of 15% of maximum voluntary contraction.
      Stretch reflex dynamics were estimated by superimposing a small stochastic
      displacement on many such stretches and using an "ensemble-based" time-varying
      identification procedure to compute impulse response functions relating the
      perturbation to the evoked electromyogram (EMG) at each point throughout the
      task. We found that stretch reflex magnitude (relating joint velocity to EMG)
      varied directly with baseline EMG activity during steady-state conditions before
      and after the large imposed stretch. Following the large stretch and the reflex
      activity it evoked, both background EMG and stretch reflex magnitude declined for
      up to 100 ms; changes in the stretch reflex were substantially greater in
      magnitude and followed a different time course from the corresponding changes in
      background EMG, however, indicating that stretch reflex properties were modulated
      independently of motoneuron pool activation level. Based on timing and the
      invariance of stretch reflex dynamics across time, it is argued that this
      behavior is largely mediated via peripheral neural mechanisms. This peripheral
      modulation of the stretch reflex presumably supplements various descending
      influences to adjust reflex properties.

PMID- 8131825
TI  - Attentional demands for static and dynamic equilibrium.
AB  - Upright standing and walking tasks require the integration of several sources of
      sensory information. In a normal and highly predictable environment, locomotor
      synergies involving several muscles may take place at lower spinal levels with
      neural circuitry tuned by local loops of assistance or self-organizing processes
      generated in coordinative networks. When ongoing regulation of gait is necessary
      (obstacles, changes in direction) supraspinal involvement is necessary to perform
      movements adapted to the environment. Using a classical information processing
      framework and a dual-task methodology, it is possible to evaluate the attentional
      demands for performing static and dynamic equilibrium tasks. The present
      experiment evaluates whether the attentional requirements for a control sitting
      condition and for standing and walking conditions vary with the intrinsic balance
      demands of the tasks. The results show that standing and walking conditions
      required more attention than sitting in a chair. The attentional cost for walking
      was also significantly greater than for standing. For the walking task, reaction
      times when subjects were in single-support phase (small base of support) were
      significantly longer than those in double-support phase, suggesting that the
      attentional demands increased with an increase in the balance requirements of the
      task. Balance control requires a continuous regulation and integration of sensory
      inputs; increasing balance demands loads the higher level cognitive system.

PMID- 8131827
TI  - H-reflexes are less depressed following muscle stretch in spastic spinal cord
      injured patients than in healthy subjects.
AB  - The size of the soleus H-reflex was measured after a slow (17 deg/s) passive
      stretch of ankle plantarflexors and compared to its control size without muscle
      stretch in ten neurologically healthy subjects and in six spastic spinal-cord
      injured patients. Two seconds after the end of the stretch, the size of the H
      reflex was reduced to about 30% of its pre-stretch size in the healthy subjects.
      The depression remained for 10-15 s. In the spastic, spinal-cord-injured
      patients, stretch caused significantly less reduction in the size of the H
      reflex. The H-reflex also regained its pre-stretch size much faster than in
      healthy subjects. We suggest that the smaller depression of the H-reflex observed
      in spastic patients may be involved in the pathophysiology of spasticity.

PMID- 8131826
TI  - Short-term synchronization of motor units in human extensor digitorum communis
      muscle: relation to contractile properties and voluntary control.
AB  - Synchronous activity was studied in relation to the contractile properties of
      pairs of motor units (MUs) recorded with independent microelectrodes in the right
      extensor digitorum communis muscle (EDC) of human subjects during isometric
      finger extension. MU contractile properties were characterized in terms of the
      rise time and amplitude of twitch tensions extracted by spike-triggered averages
      of the extension force. Synchronization of MU discharges appeared in the form of
      narrow central peaks in the cross-correlograms of 35 of 50 pairs of MUs,
      suggesting the contribution of common last-order neurons. Synchronization peaks
      tended to be briefer and higher among pairs of MUs with slower and smaller
      twitches than among pairs of MUs with faster and larger twitches. The higher
      peaks of slow-contracting MUs suggest a greater effectiveness of the common
      synaptic inputs. The broader peaks of fast-contracting MUs might reflect an
      additional synchronization of the inputs to fast MUs at high force levels. The
      areas of the cross-correlogram peaks were similar for both groups and suggest
      that under our conditions, about three motoneurons would discharge synchronously
      for a given motoneuron spike. To test whether the amount of MU synchronization
      could be altered voluntarily, four subjects attempted to increase or decrease
      synchrony, using as feedback clicks triggered by coincident firings of the
      recorded MUs. In nine of 15 conditioning sessions, the magnitudes of the
      synchronization peaks showed significant changes in the intended direction. These
      results imply that supraspinal centers can control the relative amount of inputs
      that contribute to the synchronization of motoneuron discharges during voluntary
      contraction of EDC.

PMID- 8131828
TI  - Responses of the human auditory cortex to changes in one versus two stimulus
      features.
AB  - Neuromagnetic responses were recorded with a 24-SQUID magnetometer in two
      "oddball" experiments to determine whether mismatch responses to changes in
      single stimulus features are additive. In experiment 1, the one-feature deviants
      differed from standards in interstimulus interval (ISI) or frequency, and the two
      feature deviants in both ISI and frequency. In experiment 2, deviants differed in
      duration, frequency, or both. All deviants evoked a mismatch field (MMF) with
      sources close to each other in the supratemporal auditory cortex. Except for the
      ISI deviants, the MMF sources were about 1 cm anterior to the source of the 100
      ms response, N100m, to the standards. In the two experiments, MMFs obtained in
      response to the two-feature deviants resembled closely the sum of MMFs in
      response to one-feature deviants. The results suggest that the standards leave a
      multiple neuronal representation in the human auditory cortex. The particular
      neuronal traces of the representation react independently to changes in different
      features of sound stimuli.

PMID- 8131829
TI  - Facial input to neck motoneurons: trigemino-cervical reflexes in the conscious
      and anaesthetised cat.
AB  - Cutaneous facial inputs influencing head movement were examined in the conscious
      and anaesthetised cat. EMG recordings were made in neck muscles of conscious,
      unrestrained cats in which an unexpected light cutaneous stimulus was applied to
      the glabrous skin of the planum nasale (PN). These observations established that
      head aversion movements were associated with synchronised activation of both deep
      and superficial dorsal neck muscles. In anaesthetised cats in which activity in
      the motoneurons of the large dorsal neck muscles was examined, mechanical
      stimulation of the PN or electrical stimulation of the infraorbital nerve (ION)
      produced a short latency, reflex activation. The reflex could be elicited by
      excitation of low threshold, rapidly conducting fibres in the ION. Intracellular
      recording from neck motoneurons showed that there is a short latency, probably
      disynaptic, excitatory pathway from low threshold nerves in the ION to neck
      motoneurons, but discharge of neck motoneurons occurred several milliseconds
      later, presumably as a result of activity in a longer multisynaptic pathway.

PMID- 8131830
TI  - Operant conditioning of the primate H-reflex: factors affecting the magnitude of
      change.
AB  - Primates can gradually increase or decrease H-reflex amplitude in one leg when
      reward depends on that amplitude. The magnitude of change varies greatly from
      animal to animal. This study sought to define the factors that control this
      magnitude. It evaluated the influence of animal age, muscle size (absolute and
      relative), background electromyographic activity (EMG) level, M response
      amplitude, initial H-reflex amplitude, performance intensity, and behavior of the
      contralateral leg. Fifty-four animals (Macaca nemestrina) underwent operant
      conditioning of the triceps surae H-reflex in one leg (the trained leg). Twenty
      eight were rewarded for larger H-reflexes (HRup animals), and 26 were rewarded
      for smaller H-reflexes (HRdown animals). In the HRup animals, H-reflex amplitude
      in the trained leg rose to an average final value of 177% of its initial
      amplitude. Magnitude of increase varied widely across animals. Nine animals rose
      to 120-140%, 11 to 160-240%, three to 300% or more, and five remained within 20%
      of initial amplitude. In the HRdown animals, H-reflex amplitude in the trained
      leg decreased to an average of 69% of initial amplitude. Magnitude of decrease
      varied widely. Five animals decreased to 20-40%, seven to 40-60%, six to 60-80%,
      and eight remained within 20% of initial amplitude. Animal age, as assessed by
      weight, markedly affected HRdown conditioning, but not HRup conditioning. Heavy
      HRdown animals (> or = 6 kg) were more successful than light HRdown animals (< 6
      kg). Thirteen of 14 heavy animals and only five of 12 light animals decreased to
      less than 80% of initial amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131832
TI  - An ascending spinal pathway transmitting a central rhythmic pattern to the
      magnocellular red nucleus in the cat.
AB  - The activity of cells in the magnocellular red nucleus (RNm) was recorded extra-
      and intracellularly in the curarized thalamic cat performing fictive locomotion.
      The locomotor episodes were detected from the rhythmic activity recorded in the
      motor nerves of the contralateral hindlimb. It was confirmed that, during fictive
      locomotion, a large proportion of the rubrospinal cells (56% in our sample)
      exhibit a rhythmic pattern of activity which is synchronized with the efferent
      spinal motor nerve activity. On the basis of the intracellular recordings it was
      established that phases of intense synaptic activity with mixed excitatory
      postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs)
      are involved in this rhythmicity. After eliminating the cerebellar input to the
      RNm, it was observed that the cells still received intense excitatory and
      inhibitory inputs, resulting in a continuous modulation of their membrane
      potential, due to the occurrence of EPSPs and IPSPs. During fictive locomotor
      like activity and after elimination of the cerebellar afferents to the RNm, it
      was observed that the spontaneous PSPs in RNm cells (in the case of 45% of the
      cells) were organized in repetitive subthreshold bursts occurring in phase
      relationships with the activity recorded in the motor nerves. Some
      extracellularly recorded cells (12%) showed a rhythmic firing pattern. It is
      generally recognized that, in the thalamic cat preparation, the locomotor pattern
      observed in efferent nerves originates from the central pattern generator (CPG)
      of the spinal cord. It therefore seems likely that the rhythmicity observed here
      in the RNm may originate from the spinal CPG and be transmitted through the spino
      rubral pathway ascending in the ventral part of the cord. It is concluded that
      the spino-rubral pathway may transmit both somatosensory information and
      corollary discharges relating to the activity of the spinal CPG for locomotion.

PMID- 8131831
TI  - The role of the lateral suprasylvian visual cortex of the cat in object
      background interactions: permanent deficits following lesions.
AB  - The contribution of the lateral suprasylvian cortex to pattern recognition was
      studied by behavioural detection experiments in combination with bilateral
      lesions of different parts of the lateral suprasylvian areas (LSA) and area 7 in
      seven cats. In a two-alternatives forced choice task the cats had to discriminate
      simple outline patterns which were additively superimposed on a structured visual
      background made up of broadband Gaussian noise. For various stimulus conditions
      (moving or stationary patterns and/or background) the detection probability (PD)
      of the cats was measured as a function of the signal-to-noise ratio (S/N). Each
      cat was tested before and after the lesion. Four different types of lesion could
      be distinguished depending on their extent: (1) lesion of parts of the (LSA); (2)
      lesion of parts of the LSA with undercutting of areas 17, 18 and 19; (3) lesion
      of area 7; (4) lesion of area 7 and parts of the LSA. 1. We found that a large
      bilateral lesion of the LSA led to significant deficits in all test situations
      which were dependent on the existence of relative velocity of moving patterns
      against a structured background. The ability of the cats to discriminate simple
      outline patterns which were kept stationary was not reduced. On the contrary,
      when they were tested with stationary and moving patterns on unfocused (empty)
      backgrounds, we found, to our great surprise, that the performance of the
      lesioned cats was significantly improved compared with intact animals. As these
      lesioned cats had no deficits with moving patterns on a uniformly grey
      background, we conclude that the deficits with the moving patterns must have been
      caused by interactions between patterns and background, and not by movement of a
      pattern per se. 2. As soon as the lesion of the LSA was extended by a bilateral
      undercutting of areas 17, 18 and 19 we found very severe deficits in all test
      situations, regardless of whether the patterns were moving or kept stationary, or
      whether they were superimposed on a background or not. The most substantial
      deficits occurred when the patterns were moving on a stationary background. In
      these situations the cats were no longer able to reach the 84% correct criterion.
      Again, the cats were able to reach criterion with moving patterns on a uniformly
      grey background indicating that this deficit is probably caused by the
      interaction of patterns and background and not by motion of the patterns per
      se.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8131833
TI  - Cholinergic neurons in the pedunculopontine tegmental nucleus are involved in the
      mediation of prepulse inhibition of the acoustic startle response in the rat.
AB  - The amplitude of the acoustic startle response (ASR) is markedly reduced when the
      startle eliciting pulse is preceded by a weak, non-startling stimulus at an
      appropriate lead time, usually about 100 ms. This phenomenon is termed prepulse
      inhibition (PPI) and has received considerable attention in recent years as a
      model of sensorimotor gating. We report here on experiments which were undertaken
      in order to investigate some of the neural mechanisms of PPI. We focused on the
      characterization of the cholinergic innervation of the pontine reticular nucleus,
      caudal part (PnC), an obligatory relay station in the primary startle pathway.
      The combination of retrograde tracing with choline acetyltransferase
      immunocytochemistry revealed a cholinergic projection from the pedunculopontine
      tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) to the PnC.
      Extracellular recording from single PnC units, combined with microiontophoretic
      application of the acetylcholine (ACh) agonists acetyl-beta-methylcholine (AMCH)
      and carbachol revealed that ACh inhibits the majority of acoustically responsive
      PnC neurons. Neurotoxic lesions of the cholinergic neurons of the PPTg
      significantly reduced PPI without affecting the ASR amplitude in the absence of
      prepulses. No effect on long-term habituation of the ASR was observed. The
      present data indicate that the pathway mediating PPI impinges upon the primary
      acoustic startle circuit through an inhibitory cholinergic projection from the
      PPTg to the PnC.

PMID- 8131834
TI  - Time course of locomotor recovery and functional regeneration in spinal
      transected lamprey: kinematics and electromyography.
AB  - The time course of recovery of locomotor function was examined with kinematic
      analysis and muscle recordings in larval lampreys 2-32 weeks after rostral spinal
      cord transection at the level of the third gill (approximately 10% of body
      length, BL). Animals began to recover locomotor movements within 2-4 weeks of
      spinal cord transection, but the amplitude of locomotor movements in the tail
      region was less than in normal animals. At 2 weeks post-transection, locomotor
      activity was limited to 20% BL, and at 3 weeks after spinal transection activity
      could be recorded at least as far as 40% BL. At 4 weeks after spinal transection,
      well-coordinated locomotor muscle activity was often present as far as 60% BL. At
      8 weeks of recovery and longer, well-coordinated locomotor activity was present
      consistently at least as far as 60% BL, and the amplitudes of locomotor movements
      were restored to normal values. At each recovery time examined the ranges of
      locomotor parameters (cycle time, burst proportion, and intersegmental phase lag)
      overlapped with those in normal animals. Thus, the gradual recovery of the
      amplitude of locomotor movements in the caudal body is associated with the
      gradual return of coordinated muscle activity at progressively more caudal levels
      along the body. The mechanisms responsible for this gradual recovery of locomotor
      function are discussed in relation to our recent anatomical and in vitro studies.

PMID- 8131836
TI  - Labeling of v-Src and BCR-ABL tyrosine kinases with [14C]herbimycin A and its use
      in the elucidation of the kinase inactivation mechanism.
AB  - The ansamycin antibiotic, herbimycin A, selectively inactivates cytoplasmic
      tyrosine kinases, most likely by binding irreversibly to the reactive SH group(s)
      of kinases. To further investigate the mechanism of herbimycin A action, we
      attempted to label tyrosine kinases with [14C]herbimycin A. p60v-src and p210BCR
      ABL in immune complexes were labeled with [14C]herbimycin A, demonstrating that
      the antibiotic binds directly to tyrosine kinases. Digestion of [14C]herbimycin A
      labeled p60v-src with Staphylococcus aureus V8 protease revealed that the
      herbimycin A binding site is within the C-terminal 26-kDa fragment of p60v-src,
      which contains the tyrosine kinase domain. Herbimycin A treatment inhibited
      labeling of p60v-src by [14C]fluorosulfonylbenzoyl adenosine, an affinity
      labeling reagent of nucleotide binding sites, indicating that herbimycin A
      modified p60v-src cannot interact with ATP. The results suggest that herbimycin A
      inactivates tyrosine kinases by binding directly to the kinase domain, thereby
      inhibiting access to ATP.

PMID- 8131835
TI  - A bimodal map of space: somatosensory receptive fields in the macaque putamen
      with corresponding visual receptive fields.
AB  - The macaque putamen contains neurons that respond to somatosensory stimuli such
      as light touch, joint movement, or deep muscle pressure. Their receptive fields
      are arranged to form a map of the body. In the face and arm region of this
      somatotopic map we found neurons that responded to visual stimuli. Some neurons
      were bimodal, responding to both visual and somatosensory stimuli, while others
      were purely visual, or purely somatosensory. The bimodal neurons usually
      responded to light cutaneous stimulation, rather than to joint movement or deep
      muscle pressure. They responded to visual stimuli near their tactile receptive
      field and were not selective for the shape or the color of the stimuli. For cells
      with tactile receptive fields on the face, the visual receptive field subtended a
      solid angle extending from the tactile receptive field to about 10 cm. For cells
      with tactile receptive fields on the arm, the visual receptive field often
      extended further from the animal. These bimodal properties provide a map of the
      visual space that immediately surrounds the monkey. The map is organized
      somatotopically, that is, by body part, rather than retinotopically as in most
      visual areas. It could function to guide movements in the animal's immediate
      vicinity. Cortical areas 6, 7b, and VIP contain bimodal cells with very similar
      properties to those in the putamen. We suggest that the bimodal cells in area 6,
      7b, VIP, and the putamen form part of an interconnected system that represents
      extra personal space in a somatotopic fashion.

PMID- 8131837
TI  - Nitric oxide blocks the cell cycle of mouse macrophage-like cells in the early
      G2+M phase.
AB  - The effects of nitric oxide produced by macrophage-like cells (Mm1) on the cell
      cycle were investigated. Mm1 cells lost proliferative activity in the presence of
      interleukin-6 (IL-6) and a subpopulation accumulated in the G2+M phase. This
      level increased in proportion to the incubation time. The DNA content of the
      cells was slightly lower than that of Mm1 cells treated with vinblastine or
      demecolcine, drugs which block the cell cycle in the M phase. The peak of the
      early G2+M phase was reduced by treatment with NG-mono-methyl-L-arginine.
      However, after treatment with exogenous nitric oxide or sodium nitroprusside, the
      G0/G1 phase increased, but the early-G2+M and the S phase decreased. The flow
      cytometry pattern in IL-6-treated Mm1 was the same as that of cytochalasin B
      treated Mm1. These data suggest that endogenous nitric oxide affects the
      microfilament system of IL-6-treated Mm1 cells and blocks the cell cycle in the
      early G2+M phase.

PMID- 8131838
TI  - Increase of c-jun mRNA upon hypo-osmotic cell swelling of rat hepatoma cells.
AB  - c-jun mRNA levels were increased in rat hepatoma cells (H4-II-E-C3) when exposed
      to hypotonic medium (205 mosmol/l) with a maximal induction observed after 1 h of
      hypotonic exposure. At this time point an approximate 5-fold increase in c-jun
      expression could be detected in relation to normotonic control incubations (305
      mosmol/l). Hypertonic exposure (405 mosmol/l) had only a slight effect on c-jun
      expression. In contrast to the increased c-jun mRNA levels under hypotonic
      conditions, expression of the c-fos proto-oncogene was unaffected by changes in
      the osmolarity. The hypotonicity-induced increase in c-jun expression was also
      detectable in the presence of a protein kinase C (PKC) inhibitor. This indicates
      that PKC is not involved in the signal transduction pathway leading to c-jun
      expression upon hypotonic cell swelling in these cells.

PMID- 8131839
TI  - Presence and significance of minor antenna components in the energy transfer
      sequence of the green photosynthetic bacterium Chloroflexus aurantiacus.
AB  - Antenna components in the energy transfer processes of a green photosynthetic
      bacterium Chloroflexus aurantiacus were spectrally investigated by time-resolved
      fluorescence spectroscopy at -196 degrees C on intact cells. Besides major
      antenna components so far reported, three minor components were resolved; those
      were Bchl c located at 785 nm, the baseplate Bchl a at 819 nm and Bchl a in the
      B808-866 complex at 910 nm. The last component was assigned to a longer
      wavelength antenna closely associated with a reaction center. An additional Bchl
      c fluorescence component was kinetically suggested to be present, which can be an
      energy donor to a major Bchl c. Presence of these minor components was signified
      in terms of (1) increase in the spectral overlap integral and (2) adjustment of
      the direction of dipole moments in the energy transfer sequence of intact cells.

PMID- 8131840
TI  - Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon
      gamma in stimulating the production of nerve growth factor in fibroblasts.
AB  - A possible interaction between tumor necrosis factor-alpha (TNF) and other
      cytokines/growth factors in stimulating the production of nerve growth factor
      (NGF) in Swiss 3T3 cells was studied. TNF's stimulatory activity on fibroblast
      NGF production was synergized by interleukin-1 alpha (IL-1 alpha), IL-1 beta and
      interferon-gamma (IFN-gamma), but was antagonized by transforming growth factor
      beta (TGF-beta). The most remarkable synergistic effect was observed between TNF
      and IL-1 alpha/beta; as little as 0.003 ng/ml of IL-1 beta markedly enhanced
      TNF's stimulatory activity on NGF production in the cells. These findings
      reinforce the idea that TNF, in concert with IL-1 alpha/beta, plays an essential
      role in regulating the regeneration of peripheral nerves following injury through
      an indirect mechanism by which it stimulates NGF production in fibroblasts.

PMID- 8131841
TI  - Inactivation of oncoprotein binding by a single Cys706-to-Tyr substitution in the
      retinoblastoma protein.
AB  - We previously found a new single amino acid substitution at codon 706 (Cys-to
      Tyr) of the retinoblastoma (RB) gene in a sporadic retinoblastoma patient. The
      glutathione S-transferase-RB fused protein containing this mutation was here
      tested for binding to SV40 large T antigen and adenovirus E1A protein, and was
      shown to have lost its binding affinity. Thus, Tyr, as well as Phe, residues
      substituted for Cys706 were found to abolish the RB protein activity.

PMID- 8131842
TI  - Proteolytic modification of membrane-associated phospholipase C-beta by mu
      calpain enhances its activation by G-protein beta gamma subunits in human
      platelets.
AB  - Membrane-associated phosphoinositide-phospholipase C (PI-PLC)-beta (150 kDa) and
      its truncated forms (100 kDa and 45 kDa) were purified from human platelets. The
      100 kDa PI-PLC-beta was found to be activated to a greater extent by brain G
      protein beta gamma subunits compared to the intact 150 kDa enzyme. Furthermore,
      treatment with mu-calpain of the intact PI-PLC-beta (150 kDa) caused a marked
      augmentation of its activation by beta gamma subunits. This enhanced PLC
      activation by beta gamma subunits was due to truncation by mu-calpain, producing
      a 100 kDa PI-PLC, but not by another protease, thrombin.

PMID- 8131843
TI  - Differential influence of DNA supercoiling on in vivo strength of promoters
      varying in structure and organisation in E. coli.
AB  - DNA supercoiling is known to influence promoter activity in vitro and in vivo in
      a promoter-dependent manner in prokaryotes. In order to investigate how topology
      may influence promoter function, we have studied two kinds of promoter variants,
      (i) where only the spacer region is altered, and (ii) where the same promoter is
      tandemly repeated in either the same or opposite orientation. These promoters
      respond very differently to alterations in DNA supercoiling, suggesting that the
      overall structure of the promoter and its context contribute to the differential
      response to alterations in supercoiling in vivo.

PMID- 8131844
TI  - Involvement of plasma membrane-located calmodulin in the response decay of cyclic
      nucleotide-gated cation channel of cultured carrot cells.
AB  - Increase in cytoplasmic cyclic AMP concentration stimulates Ca2+ influx through
      the cyclic AMP-gated cation channel in the plasma membrane of cultured carrot
      cells. However, the Ca2+ current terminated after a few minutes even in the
      presence of high concentrations of cyclic AMP indicating that hydrolysis of the
      nucleotide is not responsible for stop of the Ca2+ influx. Cyclic AMP evoked
      discharge of Ca2+ from inside-out sealed vesicles of carrot plasma membrane, and
      it was strongly inhibited when the suspension of the vesicles was supplemented
      with 1 microM of free Ca2+, while Ca2+ lower than 0.1 microM did not affect the
      Ca(2+)-release. The Ca2+ flux across plasma membrane was restored from this
      Ca(2+)-induced inhibition by the addition of calmodulin inhibitors or anti
      calmodulin. These results suggest that Ca2+ influx initiated by the increase in
      intracellular cAMP in cultured carrot cells is terminated when the cytosolic Ca2+
      concentration reaches the excitatory level in the cells, and calmodulin located
      in the plasma membrane plays an important role in the response decay of the
      cyclic nucleotide-gated Ca2+ channel.

PMID- 8131845
TI  - The role of the ninth and tenth type III domains of human fibronectin in cell
      adhesion.
AB  - Fibronectins (FN) contain sites, in addition to the cell recognition site RGD in
      the tenth type III domain (FIII10), that are required for adhesive activity. The
      role of FIII10 and the adjacent FIII9 was analysed in functional cell adhesion
      assays recombinant FIII domains in which the domain boundaries were strictly
      conserved. FIII9 had no adhesive activity. FIII10, and FIII9 plus FIII10 had less
      activity than FN, whereas the activity of FIII9-10 was similar to FN. We conclude
      that FIII9 acts synergistically with FIII10 in cell adhesion, and that this
      synergy is dependent upon the structural integrity of the FIII9-10 pair of
      domains.

PMID- 8131846
TI  - Predicted topology of the N-terminal domain of the hydrophilic subunit of the
      mannose transporter of Escherichia coli.
AB  - A folding topology for the homodimeric N-terminal domain (IIA, 2 x 14 kDa) of the
      hydrophilic subunit (IIABman) of the mannose transporter of E. coli is proposed.
      The prediction is based on (i) tertiary structure prediction methods, and (ii)
      functional properties of site-directed mutants in correlation with NMR-derived
      alpha/beta secondary structure data. The 3D structure profile suggested that the
      overall fold of IIA is similar to that of the unrelated protein, flavodoxin,
      which is an open-stranded parallel beta-sheet with a strand order of 5 4 3 1 2.
      The 3D model of IIA, constructed using the known atomic structure of flavodoxin,
      is consistent with the results from site-directed mutagenesis. Recently NMR
      results confirmed the open parallel beta-sheet with a strand order of 4 3 1 2
      (residues 1-120) of our model whereas beta-strand 5 (residues 127-130) was shown
      to be antiparallel to beta-strand 4. The correctly predicted fold includes 90% of
      the monomeric subunit sequence and contains all functional sites of the IIA
      domain.

PMID- 8131847
TI  - On the two forms of bacteriorhodopsin.
AB  - In our previous work [(1993) FEBS Lett. 313, 248-250; (1993) Biochem. Int. 30,
      461-469] M-intermediate formation of wild-type bacteriorhodopsin was shown to
      involve two components differing in time constants (tau 1 = 60-70 microseconds
      and tau 2 = 220-250 microseconds), which were suggested to reflect two
      independent pathways of M-intermediate formation. The contribution of the fast M
      was 4-times higher than the slow one. Our present research on M-intermediate
      formation in the D115N bacteriorhodopsin mutant revealed the same components but
      at a contribution ratio of 1:1. Upon lowering the pH, the slow phase of M
      formation vanished at a pK of 6.2, and in the pH region 3.0-5.5 only the M
      intermediate with a rise time of 60 microseconds was present. A 5-6 h incubation
      of D115N bacteriorhodopsin at pH 10.6 resulted in the irreversible transformation
      of 50% of the protein into a form with a difference absorbance maximum at 460 nm.
      This form was stable at pH 7.5 and had no photocycle, including M-intermediate
      formation. The remaining bacteriorhodopsin contained 100% fast M-intermediate.
      The disappearance of the 250-microseconds phase concomitant with bR460 formation
      indicates that at neutral pH bacteriorhodopsin exists as two spectroscopically
      indistinguishable forms.

PMID- 8131848
TI  - Human complement component C8. Molecular basis of the beta-chain polymorphism.
AB  - The beta-chain of human complement component C8 exhibits a structural genetic
      polymorphism: using isoelectric focusing two major allotypes can be identified
      (C8B B ('basic') and C8B A ('acidic')). In the present report we describe a
      sequence polymorphism of the C8B gene (codon 63: AGA-->GGA) and demonstrate that
      the resulting amino acid substitution (Arg-->Gly) consistently differentiates
      between the two common charge variants of the C8 beta chain; the C8B B allotype
      is characterized by an Arg and the C8B A allotype by a Gly residue in position 63
      of the C8 beta polypeptide chain.

PMID- 8131849
TI  - Insulin inhibits glucocorticoid-induced stimulation of liver 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase gene transcription.
AB  - 6-Phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (FBPase-2) catalyzes
      the synthesis and degradation of fructose 2,6-bisphosphate, a potent stimulator
      of glycolysis. Transcription of the mRNA encoding rat liver PFK-2/FBPase-2 is
      stimulated by insulin and by glucocorticoids in rat hepatoma cells. We show here
      that insulin can also prevent and reverse this glucocorticoid effect. The
      inhibitory effect of insulin is independent of extracellular glucose and does not
      require ongoing protein synthesis. We conclude that insulin exerts opposite
      effects on PFK-2/FBPase-2 gene transcription depending on the hormonal context.

PMID- 8131850
TI  - Specific receptors for adrenomedullin in cultured rat vascular smooth muscle
      cells.
AB  - The effects of synthetic rat adrenomedullin (rAM), a novel vasorelaxant peptide
      originally isolated from human pheochromocytoma, on receptor binding and cAMP
      generation were studied in cultured rat vascular smooth muscle cells (VSMC). A
      binding study using [125I]rAM revealed the presence of a single class of high
      affinity (Kd 1.3 x 10(-8) M) binding sites for rAM in VSMC. The apparent Ki of
      rat calcitonin gene-related peptide (rCGRP) was 3 x 10(-7) M. Affinity labeling
      of VSMC membranes with [125I]rAM revealed two distinct labeled bands with
      apparent molecular weights of 120 and 70 kDa, both of which were abolished by
      excess unlabeled rAM or rCGRP, rAM stimulated cAMP formation with an approximate
      EC50 of 10(-8) M, the effect of which was additive with isoproterenol, but not
      with rCGRP. The rAM-induced cAMP response was unaffected by propranolol,
      indomethacin, or quinacrine, but inhibited by a CGRP receptor antagonist, human
      CGRP[8-37]. These data suggest that VSMC possesses specific AM receptors
      functionally coupled to adenylate cyclase with which CGRP interacts.

PMID- 8131851
TI  - Identification of in vivo phosphorylation sites of SET, a nuclear phosphoprotein
      encoded by the translocation breakpoint in acute undifferentiated leukemia.
AB  - SET, the translocation breakpoint-encoded protein in acute undifferentiated
      leukemia (AUL), is identified as a 39-kDa phosphoprotein found predominantly in
      the cell nuclei [1994, J. Biol. Chem. 269, 2258-2262]. SET is fused to a putative
      oncoprotein, CAN, in AUL and is thought to regulate the transformation potential
      of SET-CAN by its nuclear localization and phosphorylation. We investigated in
      detail the in vivo phosphorylation of SET. Phosphorylation of SET occurred in all
      human cell lines examined in vivo, primarily on serine residues. Endoproteinase
      Glu-C digestion of phosphorylated SET yielded two phosphopeptides. By
      radiosequencing, we identified the in vivo phosphorylation sites of SET as Ser9
      and Ser24. The surrounding sequences of Ser9 and Ser24 contained an apparent
      consensus site sequence for protein kinase C.

PMID- 8131852
TI  - Abundant expression of thromboxane synthase in rat macrophages.
AB  - The cloned cDNA for rat thromboxane (TX) synthase with a size of 1851 bp
      contained a 1599-bp open reading frame which encoded a 533-amino acid protein
      sharing 79.7% identity with human TX synthase. RNA blot analysis was carried out
      with rat cells and tissues. Rat peritoneal macrophages most abundantly expressed
      mRNA for TX synthase, and its level was not changed by in vivo stimulation of
      casein. Bone marrow, spleen, lung and thymus also expressed the TX synthase gene.
      These findings suggest the possibility that TXA2 plays a role in the immune
      system.

PMID- 8131853
TI  - Human-Xenopus chimeras of Gs alpha reveal a new region important for its
      activation of adenylyl cyclase.
AB  - G proteins are heterotrimeric GTPases that play a key role in signal
      transduction. The alpha subunit of Gs bound to GTP is capable of activating
      adenylyl cyclase. The amino acid sequences derived from two X. laevis cDNA clones
      that apparently code for Gs alpha subunits are 92% identical to those found in
      the short form of human Gs alpha. Despite this high homology, the X. laevis Gs
      alpha clones expressed in vitro, yielded a protein that are not able to activate
      the adenylyl cyclase present in S49 cyc- membranes in contrast with human Gs
      alpha similarly expressed. This finding suggested that the few amino acid
      substitutions found in the amphibian subunit are important in defining the
      functionality of the human Gs alpha. The construction of chimeras composed of
      different fractions of the cDNAs of the two species was adopted as an approach in
      determining the regions of the molecule important in its functionality in this
      assay. Four pairs of chimeras were constructed using reciprocal combinations of
      the cDNAs coding for human and Xenopus Gs alpha. These eight constructs were
      expressed in vitro and equivalent amounts of the resulting proteins were assayed
      in the activation of adenylyl cyclase with GTP gamma and isoproterenol. The
      results obtained here clearly indicate that the G alpha sequence that extends
      from amino acid 70 to 140, is important for the functionality of human Gs alpha
      in activating adenylyl cyclase.

PMID- 8131854
TI  - The 3D structure of a cyclosporin analogue in water is nearly identical to the
      cyclophilin-bound cyclosporin conformation.
AB  - The conformation of [D-MeSer3-D-Ser-(O-Gly)8]CS, a water soluble cyclosporin
      derivative, has been determined in (D6)DMSO and in water using NMR. In these
      polar solvents the conformation is identical and very similar to the structure
      found in the cyclophilin-cyclosporin complex. However, it differs significantly
      from its conformation in deuterated chloroform. This demonstrates unambiguously
      that the large structure change is induced primarily by the polar solvent rather
      than by complex formation with cyclophilin.

PMID- 8131855
TI  - Organization and chromosomal localization of the gene for the human bombesin
      receptor subtype expressed in pregnant uterus.
AB  - The gene encoding the human homologue of the guinea pig uterine bombesin receptor
      [(1992) Eur. J. Biochem. 208, 405] was isolated from a genomic lambda library by
      the PCR/homology screening approach. The gene spans more than 4 kb and consists
      of 3 exons and 2 introns. The deduced amino acid sequence shows about 86%
      identity to that of guinea pig bombesin receptor. This subtype of bombesin
      receptor is expressed in the pregnant uterus and in two human tumour cell lines,
      T47D (ductal breast carcinoma) and A431 (epidermal carcinoma). PCR analysis of
      genomic DNA from human-mouse cell hybrids allows the cloned gene to be localized
      to the region q26-q28 on chromosome X.

PMID- 8131856
TI  - Photoaffinity cross-linking of F1ATPase from spinach chloroplasts by 3'-arylazido
      beta-alanyl-8-azido ATP.
AB  - UV irradiation of the ATPase (CF1) from spinach chloroplasts in the presence of
      3'-arylazido-beta-alanyl-8-azido ATP (8,3'-DiN3ATP) results in a nucleotide
      dependent inactivation of the enzyme and in a nucleotide-dependent formation of
      alpha-beta cross-links. The results demonstrate an interfacial localization of
      the nucleotide binding sites on CF1.

PMID- 8131857
TI  - Activation of mitogen activated protein (MAP) kinases by vanadate is independent
      of insulin receptor autophosphorylation.
AB  - Treatment of Chinese hamster ovary (CHO) cells over-expressing the human insulin
      receptor (CHO-HIRc) with the insulin mimetic agent, vanadate, resulted in a dose-
      and time-dependent tyrosine phosphorylation of two proteins with apparent
      molecular sizes of 42 kDa (p42) and 44 kDa (p44). However, vanadate was unable to
      stimulate the tyrosyl phosphorylation of the beta-subunit of the insulin
      receptor. By using myelin basic protein (MBP) as the substrate to measure mitogen
      activated protein (MAP) kinase activity in whole cell lysates, vanadate
      stimulated tyrosyl phosphorylation of p42 and p44 was associated with a dose- and
      time-dependent activation of MAP kinase activity. Furthermore, affinity
      purification of cell lysates on anti-phosphotyrosine agarose column followed by
      immunoblotting with a specific antibody to MAP kinases demonstrated that vanadate
      treatment increased the tyrosyl phosphorylation of both p44mapk and p42mapk by
      several folds, as compared to controls, in concert with MAP kinase activation. In
      addition, retardation in gel mobility further confirmed that vanadate treatment
      increased the phosphorylation of p44mapk and p42mapk in CHO-HIRc. A similar
      effect of vanadate on MAP kinase tyrosyl phosphorylation and activation was also
      observed in CHO cells over-expressing a protein tyrosine kinase-deficient insulin
      receptor (CHO-1018). These results demonstrate that the protein tyrosine kinase
      activity of the insulin receptor may not be required in the signaling pathways
      leading to the vanadate-mediated tyrosyl phosphorylation and activation of MAP
      kinases.

PMID- 8131858
TI  - Ca2+ influx evoked by inositol-3,4,5,6-tetrakisphosphate in ras-transformed
      NIH/3T3 fibroblasts.
AB  - Infusion of inositol-3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4) from the patch
      pipette into the cytoplasm, produced a biphasic intracellular free Ca2+
      concentration ([Ca2+]i) increase in ras-transformed NIH/3T3 (DT) cells. The
      Ins(3,4,5,6)P4-induced increase in DT cells depended upon extracellular Ca2+, and
      was enhanced by membrane hyperpolarization. Identical [Ca2+]i increases were
      observed with intracellular application of inositol-1,3,4,5-tetrakisphosphate
      (Ins(1,3,4,5)P4) and inositol-1,3,4,6-tetrakisphosphate but not with inositol
      1,2,4,5-tetrakisphosphate, inositol-1,4,5-trisphosphate or inositol-1,3,4,5,6
      pentakisphosphate. Stimulation of DT cells with bradykinin increased the levels
      of Ins(3,4,5,6)P4 and Ins(1,3,4,5)P4. These results suggest that Ins(3,4,5,6)P4
      may serve as a second messenger for continuous Ca2+ influx along with other
      tetrakisphosphates downstream from bradykinin receptors in DT cells.

PMID- 8131859
TI  - Formation of sulphmyoglobin during expression of horse heart myoglobin in
      Escherichia coli.
AB  - Expression of recombinant horse heart myoglobin in Escherichia coli has been
      found to result in the production of both native and variable amounts
      (approximately 16-17% total) of two sulphmyoglobin isomers. The recombinant
      sulphmyoglobin produced consists primarily of the A and B isomers as identified
      by 1H NMR spectroscopy with no evidence for production of the C isomer.
      Conversion of recombinant sulphmyoglobin to the native protein can be achieved by
      reconstitution with protohaem IX. The possible relationship of this observation
      to recombinant expression of other heme proteins is discussed.

PMID- 8131860
TI  - Endurance training alters alanine and glutamine release from muscle during
      contractions.
AB  - The release of alanine and glutamine from perfused muscle of trained and control
      animals was investigated. Release rates did not differ between trained and
      control muscle at rest. During contractions in trained muscle, alanine release
      was higher than at rest, while glutamine release was transiently increased.
      Phenylalanine release did not differ between trained and control muscle, implying
      that protein degradation was not increased in trained muscle. The muscle cellular
      adaptations to training include a selective modification of amino acid output,
      which could potentially influence gluconeogenic flux and alter muscle ammonia
      levels during contractions.

PMID- 8131861
TI  - GTP-binding protein-activator sequences in the insulin receptor.

PMID- 8131862
TI  - Carcinoma of the pancreas--the Jefferson experience 1975-1988.
AB  - A retrospective review of 410 patients with carcinoma of the pancreas seen at
      Thomas Jefferson University from 1975-1988 was undertaken to provide a global
      view of the effectiveness of different modalities of treatment in the management
      of this disease. There were seven patients with Stage I disease, 141 patients
      with Stage II disease, 91 with Stage III, and 171 with Stage IV disease. The
      overall median survival was 7 months and a 1-year survival of 30% was observed.
      Median survival was 15 months for Stage I, 10 months for Stage II, 9 months for
      Stage III and 4 months for Stage IV patients. Several treatment approaches were
      utilized in these patients. Twenty-three patients underwent surgical resection.
      Five of these had Stage I tumor, and 18 patients had Stage II or III disease.
      Median survival in this group was 12 months with an operative mortality of 13%.
      No resected patients survived greater than 3 years. Eleven patients with Stage II
      and III disease received chemotherapy alone, 28 patients received external
      radiation alone, and 30 patients received Iodine-125 implantation plus external
      radiation. Median survival in all three groups was 7 months. Forty-five patients
      received combined chemotherapy plus external radiation for Stage II and III
      cancer with a median survival of 10 months and a 2-year survival of 14%. Eighty
      one patients received combined Iodine-125 implantation+external
      radiation+chemotherapy and had a median survival of 13 months and a 2-year
      survival of 22%. Local control of disease was achieved in 74% of these patients.
      This combined modality approach appears to have the best potential for control of
      primary cancer and long-term survival of selected patients.

PMID- 8131863
TI  - Squamous carcinoma of the oesophagus. Surgery alone or combined with
      perioperative radiotherapy?
AB  - A retrospective comparison of surgery alone and surgery combined with pre- and
      post-operative radiotherapy was performed for the treatment of squamous carcinoma
      of the mid and upper oesophagus. Twenty-five ostensibly curative resections for
      squamous carcinoma of the oesophagus were performed in the period 1974-1987 by
      the Lewis oesophagectomy. Patients were well matched for histological stage, sex
      (14F 11M) and age (range 23-69 years). Five year survival for patients receiving
      surgery alone was 54.5%. Survival for patients who in addition received
      adjunctive pre- and postoperative radiotherapy of 5700 cGY was not significantly
      different. Adjunctive pre- and post-operative radiotherapy was considered to
      facilitate surgical resections but long term survival was not improved.

PMID- 8131864
TI  - Squamous cell carcinoma of the oesophagus with mucin-secreting component (muco
      epidermoid carcinoma and adenosquamous carcinoma): a clinicopathologic study and
      a review of literature.
AB  - The clinicopathological features of 11 cases of primary oesophageal squamous cell
      carcinomas with mucin-secreting component (eight muco-epidermoid and three
      adenosquamous carcinomas) are presented. The incidence was 2.2% of all resected
      primary oesophageal tumors. The mean age was 64 years and the male to female
      ratio was 4.5:1. The mean diameter of these tumours was 4 cm. Twenty-seven per
      cent of these tumours were in the upper, 46% in the middle and 27% in the lower
      portion of the oesophagus. The age, sex and site distribution of these tumors
      were similar to those of squamous cell carcinomas. The medium survival of these
      patients was 15 months. The world literature concerning this rare entity was
      reviewed and compared with the findings of the present study. No major racial
      differences were noted. In addition, the classification of this group of tumours
      was also discussed.

PMID- 8131865
TI  - Soft tissue sarcoma of the extremity.

PMID- 8131866
TI  - Pleural effusion in breast cancer: a review of the Nottingham experience.
AB  - A retrospective analysis of 40 patients with pleural effusions caused by breast
      cancer is presented. Evidence is presented which suggests that malignant pleural
      effusion in breast cancer is caused by lymphatic rather than blood spread. 70% of
      effusions are ipsilateral to the primary carcinoma and 22.5% of patients with
      pleural effusions have positive internal mammary node biopsies (compared to 10.4%
      in controls). 47.5% of effusions had positive cytology but this does not
      correlate with either survival or recurrence. In operable tumours, pleural
      effusion is correlated with the size of the primary tumour but effusions were
      uncommon with large, locally advanced Stage III tumours at presentation, which
      could be attributable either to the short survival of such patients or to the
      effect of adjuvant radiotherapy reducing the chance of an ipsilateral effusion.
      Although these patients overall had a short life expectancy (median 11 months)
      there was a wide range. Chest drainage and instillation of 100 mg mepacrine in 30
      ml of bupivacaine to give rise to pleurodesis offers useful palliation and
      minimizes recurrence (29 treatments with only two symptomatic recurrences),
      compared with aspiration alone (19 treatments with 12 symptomatic recurrences) or
      instillation with tetracycline (10 treatments with five symptomatic recurrences).
      Pleural effusion secondary to breast cancer is a locoregional manifestation.
      Pleurodesis with mepacrine offers good local control.

PMID- 8131867
TI  - Aspirative cytology with fine-needle in the abdomen, retroperitoneum and pelvic
      cavity: a seven year experience of the Portuguese Institute of Oncology, Center
      of Porto.
AB  - A review was made of 236 fine-needle aspiration cytologies (FNAC), guided by
      ultrasound, computerized tomography or fluoroscopy, performed in the abdomen,
      retroperitoneum and pelvic cavity. Seventy-three FNAC were from the liver, 41
      from the kidneys, 30 from the pelvic cavity, 26 from the retroperitoneum, 24 from
      the peritoneal cavity, 13 from the pancreas, 11 from the adrenal glands, nine
      from the abdominal wall, seven from the spleen and two from the digestive tract.
      The total accuracy rate was 90%, ranging from 77% in the abdominal wall lesions
      to 100% in the splenic lesions. Indications for FNAC and results are discussed as
      well as the accuracy rate obtained with different guiding modalities. We conclude
      considering FNAC a safe, unexpensive and reliable method to confirm the diagnosis
      of malignant lesions in the abdomen, retroperitoneum and pelvic cavity.

PMID- 8131868
TI  - Prevalence of sexual dysfunction in male cancer patients treated with rectal
      excision and coloanal anastomosis.
AB  - Impotency due to parasympathetic nerve injury is one of the most feared
      consequences of rectal cancer surgery. Sexual relationships make a significant
      contribution to the quality of life for almost everybody. Rectal excision and
      coloanal anastomosis (CAA) is a new surgical procedure for low rectal tumor with
      little data regarding the prevalence of sexual impairment as yet. We have
      examined the sexual life of 21 male patients who have undergone CAA by means a
      self-administered questionnaire. Only two patients reported reactive impotency.
      On the other hand 17 out of 21 patients had no ejaculation after undergoing
      surgery. According to our data it appears that CAA results in surgery a low
      degree of sexual impairment (impotency). Both sexual dysfunction and quality of
      life investigations should be integrated with oncological results when reporting
      data about colorectal surgery.

PMID- 8131869
TI  - Small bowel tumors: an analysis of tumor-like lesions, benign and malignant
      neoplasms.
AB  - The clinical records of 72 patients with 73 small bowel tumors diagnosed over a
      period of 25 years were reviewed. The tumors consisted of 23 tumor-like lesions,
      17 benign neoplasms and 33 malignant neoplasms, the mean size of which were 2.1
      cm, 5.2 cm and 7.7 cm in diameter, respectively. The tumor-like lesions and
      benign neoplasms were found even in children, while the malignant neoplasms were
      observed in patients 43 years old or over. The most common tumor-like lesion was
      aberrant pancreatic tissue. The common benign neoplasms were leiomyoma, lipoma
      and adenoma. The malignant neoplasms consisted of adenocarcinoma, malignant
      lymphoma and leiomyosarcoma. Regardless of tumor type or tumor location, the
      lesions 4 cm or larger often caused abdominal symptoms. Most of the lesions less
      than 4 cm caused no symptoms, but the malignant lesions of this size in the ileum
      elicited abdominal symptoms in all patients. The presence of lesions was
      diagnosed preoperatively in 26.1% of patients with tumor-like lesions, 47.1% with
      benign neoplasms and 48.5% with malignant neoplasms. Resection was performed in
      all but one patient with tumor-like lesions and benign neoplasms. Among malignant
      lesions, the resectability rate was 80.0% for adenocarcinoma and 100% for both
      malignant lymphoma and leiomyosarcoma. However, the patients with malignant
      lesions showed a poor prognosis. In conclusion, it is important to recognize
      small bowel tumors--especially malignant lesions--as a rare but possible cause of
      abdominal symptoms and thereby to contribute to the early detection and
      successful management of small bowel tumors.

PMID- 8131870
TI  - Post irradiation sarcoma of soft tissue and bone.
AB  - Thirty-eight patients with sarcomas of soft tissue and bone which followed
      previous radiotherapy have been treated at the Royal Marsden Hospital between
      1951 and 1992. The commonest reasons for initial radiotherapy were carcinoma of
      the breast and lymphoma, and the median time to development of sarcoma was 11
      years. The only long term survivors were those who had complete surgical
      excision. Seven patients required forequarter amputation (30% of the extremity
      sarcomas) which reflects their frequent situation in the shoulder girdle and
      upper arm and the close proximity to the brachial plexus and vascular bundle. The
      overall prognosis was poor (5-year survival 30%) and probably reflects the poor
      prognostic factors (size, grade and tumour site) present at the time of
      diagnosis.

PMID- 8131871
TI  - Oncogenic osteomalacia induced by schwannoma in a patient with neurofibromatosis.
AB  - A 62-year-old woman known to be suffering from Von Recklinghausen disease and
      osteomalacia was operated on for a pelvic mass. Pathological examination of the
      excised tumor showed it to be a schwannoma and this tumor was considered to be
      responsible for the osteomalacia. The return of previously abnormal laboratory
      data to normal values and the impressive clinical and subjective improvement
      further support the assumption that the excised schwannoma was responsible for
      the pathology observed in this patient.

PMID- 8131872
TI  - Synchronous double malignant tumors of the gall bladder. A case-report of
      squamous cell carcinoma with an angiosarcoma.
AB  - The first case of synchronous double malignant tumors of the gall bladder having
      squamous cell carcinoma and an angiosarcoma at different sites is being reported
      in the world literature. The etiologic, diagnostic and therapeutic aspects of
      these malignancies and the significance of their concurrence are discussed.

PMID- 8131873
TI  - Large mesenteric mass caused by a mesenteric desmoid tumour.
AB  - A very large mesenteric desmoid tumour was found in a 19-year-old man. The tumour
      could be excised with free margins and no further therapy was given. One year
      after the operation the patient does well without any signs of recurrence.

PMID- 8131874
TI  - Clinicopathological study of the diffuse sclerosing variety of papillary cancer
      of the thyroid. Presentation of 4 new cases and review of the literature.
AB  - A new variant of papillary carcinoma of the thyroid is analysed, known as
      'diffuse sclerosing'. This lesion is characterized by a papillary cancer with a
      marked lymphocytic infiltration, intense fibrosis and a large number of psammoma
      bodies. Of a population of 158 differentiated thyroid carcinomas, we found four
      cases of this rare variant. The clinicopathological characteristics were studied
      together with the importance of an accurate diagnosis and prognosis, and the data
      obtained were compared with those of a 'well-differentiated or classical'
      papillary cancer, which yielded the following outstanding features: (a) younger
      age of presentation; (b) greater affinity for males; (c) greater frequency of
      extrathyroid extension; and (d) greater frequency of recurrences. The clinical
      importance of recognizing this variant is based on the need to apply a more
      aggressive treatment and a more exhaustive follow-up to such patients.

PMID- 8131875
TI  - Basic principles of radiotherapy for surgical oncologists. 1--Effects of
      radiotherapy on superficial tissues. Implications for treating skin cancer.

PMID- 8131876
TI  - How I minimize morbidity in axillary dissection.

PMID- 8131877
TI  - Adhesion molecules in cancer.

PMID- 8131878
TI  - Surgical video review--radical gastrectomy.

PMID- 8131879
TI  - Malaria in stone quarry area of Faridabad complex (Haryana).
AB  - An analysis of five-year (1987-91) epidemiological data showed that the stone
      quarries contributed, on an average, 38.7% of malaria cases to the total of
      Faridabad Town and 11.6% to that of Faridabad district. Various malariometric
      indices like Annual Parasite Incidence (API), Annual Blood Examination Rate
      (ABER), Slide Positivity Rate (SPR) and Slide falciparum Rate (SfR) were analysed
      to assess the endemicity of disease, and attempts were made to compare them with
      the malaria parameters of the town and then of the district. Migrant population
      working as labour in stone quarries resides in areas conducive to malaria and
      hence the need for intensive control measures.

PMID- 8131880
TI  - Prevalence and seasonal distribution of anopheline fauna in district Bikaner
      (Rajasthan).
AB  - A survey was carried out during 1989-91 to study the prevalence and distribution
      of anopheline mosquitoes in 12 villages located in all the 4 tehsils of Bikaner
      district. Six species, viz. Anopheles subpictus (34.7%), An. stephensi (33.3%),
      An. culicifacies (18.0%), An. annularis (12.1%), An. pulcherrimus (1.1%) and An.
      barbirostris (0.8%), were collected. An. stephensi was present throughout the
      year and the other species were present during the monsoon and post-monsoon
      periods. During the peak winter period (Dec-Jan) only An. stephensi was present
      and in low density. An. culicifacies made its appearance only during the spring
      season and continued up to the middle of November. An. subpictus, An.
      pulcherrimus, An. barbirostris and An. annularis were found only during the
      monsoon and post-monsoon periods. An. subpictus was the most abundant species
      during the monsoon, and so was An. stephensi during the spring season in indoor
      habitats.

PMID- 8131881
TI  - Oxidative stress and antioxidant defence mechanism in Plasmodium vivax malaria
      before and after chloroquine treatment.
AB  - The protection of Plasmodium vivax-parasitized red blood cells (PRBCs) against
      activated forms of oxygen was examined in relation to the non-parasitized and
      chloroquine-treated red blood cells. Increased parasitaemia was found to be
      accompanied with a decrease in the activities of enzymes of the glutathione
      system, namely glutathione peroxidase (GPx), glutathione reductase (GRx) and
      glutathione S-transferase (GTr) in the red blood cells (RBC) lysates. In
      contrast, however, the total amount of reduced glutathione (GSH) and the content
      of water-soluble antioxidant vitamin C was increased 2-3 fold over those of
      control RBCs. Chloroquine-treated red cells contained enzyme activities and
      antioxidant contents (GSH, vitamin C) comparable to those of control and non
      parasitized red cells. Our results therefore indicate the oxidative stress
      experienced by RBCs during P. vivax infection and that this infection is
      accompanied with changes in the antioxidant defence system of the host, which are
      restored to near normal levels after treatment with chloroquine.

PMID- 8131882
TI  - Anopheline fauna and malaria incidence in Changlang District (Arunachal Pradesh).
AB  - Data on malaria incidence and prevalence as well as on abundance of anopheline
      species collected in Jairampur, Arunachal Pradesh, show that P. falciparum
      contributed 27.59% of the total positive cases, most of these being recorded
      during July to September. Of the twelve anopheline species recorded, Anopheles
      maculatus was the most predominant comprising 54.32% of the total collection.
      Other common species were An. peditaeniatus, An. philippinensis and An. kochi in
      order of decreasing proportion. An. dirus, the known vector, was collected in the
      whole-night human bait catches (indoor) but in low numbers. An. philippinensis is
      implicated as another potential vector, and changes in anopheline/vector fauna
      are attributed to ecological succession.

PMID- 8131883
TI  - Role of An. culicifacies and An. stephensi in malaria transmission in urban
      Delhi.
AB  - Studies on adult densities, vector incrimination and breeding habitats of An.
      culicifacies and An. stephensi were carried out during June 1984 to May 1986 in
      three different ecological areas of urban Delhi. Both An. culicifacies and An.
      stephensi prevailed throughout the year in peri-urban areas with higher densities
      during the post-monsoon months. In south and northwest areas, low densities of
      these vector species were recorded. An. culicifacies was found naturally infected
      with sporozoites in peri-urban and south areas, whereas An. stephensi showed
      gland infection in south areas only. Out of 827 blood smears collected, 302 were
      positive for malaria parasites. Of the positives, P. vivax formed 48.3% and P.
      falciparum 51.7%. Peri-urban areas showed a higher number of malaria cases than
      south and northwest areas.

PMID- 8131884
TI  - Use of kerosene lamp containing synthetic pyrethroids to repel mosquitoes.
AB  - An indigenous and appropriate method of personal protection was developed and
      tested in rural areas. It consists of an ordinary kerosene lamp made of tin with
      a regulator to adjust the wick. Different concentrations of esbiothrin, a
      synthetic pyrethroid, were mixed in kerosene and allowed to burn in living rooms
      and cattlesheds from dusk to dawn to observe hourly entry of mosquitoes. The tin
      lamp (100 ml capacity) without chimney provided the most efficient protection
      from mosquito bites. The protection varied from 84.2 +/- 8.2 to 97.8 +/- 2.8.
      Maximum protection was observed against An. culicifacies. Esbiothrin kerosene
      lamp (0.01%) lighted in living room provided 99.7% protection to exposed human
      baits seated at a distance of 1 m from the lamp. The technique is simple, cost
      effective and does not require electricity and can be used both for illumination
      and repelling mosquitoes in remote and inaccesible areas.

PMID- 8131885
TI  - Screening of Coptis teeta Wall. for antimalarial effect: a preliminary report.

PMID- 8131886
TI  - Homologous sugar-transport proteins in microbes and man.

PMID- 8131887
TI  - Multiple mechanisms, roles and controls of K+ transport in Escherichia coli.

PMID- 8131888
TI  - Proton-translocating transhydrogenase in bacteria.

PMID- 8131889
TI  - P-450 biotechnology.

PMID- 8131890
TI  - Applications of molecular biology and in vitro technology to drug metabolism
      studies: an industrial perspective.

PMID- 8131891
TI  - Genetic toxicology using human cell lines expressing human P-450.

PMID- 8131892
TI  - Xenobiotic metabolism in humanized yeast: engineered yeast cells producing human
      NADPH-cytochrome P-450 reductase, cytochrome b5, epoxide hydrolase and P-450s.

PMID- 8131893
TI  - Molecular genetic analysis of azole antifungal mode of action.

PMID- 8131894
TI  - Resistance of Candida albicans to azole antifungal agents.

PMID- 8131895
TI  - Resistance to azole fungicides in the field.

PMID- 8131896
TI  - Biochemical characterization of tobacco mutants resistant to azole fungicides and
      herbicides.

PMID- 8131897
TI  - Cytochrome P-450 as a target for therapeutic inhibitors.

PMID- 8131898
TI  - Insect cytochrome P-450: metabolism and resistance to insecticides.

PMID- 8131899
TI  - Potentiation of pesticide toxicity in birds: role of cytochrome P-450.

PMID- 8131900
TI  - Plant cytochrome P-450 and agricultural biotechnology.

PMID- 8131901
TI  - Efficiency and substrate specificity of Streptomyces griseolus cytochromes P
      450SUI and P-450SU2 mono-oxygenase reactions.

PMID- 8131902
TI  - Microbial transformations of steroids.

PMID- 8131903
TI  - Heterologous expression of cytochrome P-450 in Escherichia coli.
AB  - While the bacterial expression system has proved to work well for the expression
      of functional forms both of microsomal and of mitochondrial P-450, we understand
      the requirements for expression in bacteria far less clearly than those for
      expression in eukaryotic cells. Nevertheless, the ability to generate large
      quantities of P-450 (Table 1) in an inexpensive culture system, the ease of site
      directed mutagenesis in bacteria and the ability to purify easily relatively
      large quantities of P-450s, including human enzymes that are not normally
      available, make this a particularly useful expression system for P-450
      structure/function analysis. Furthermore, the background of P-450 level in E.
      coli is extremely low. It appears that the minor sequence alterations that have
      been made at the N-terminus to achieve high expression do not alter the enzymic
      properties of the recombinant P-450s, and it will not be surprising if vector
      systems are developed where such changes are not necessary. One concern with
      bacterial expression of P-450 is whether this system will prove of general use.
      Preliminary data suggests that certain mutant forms of human P-450c17 that are
      known to be functional in COS cells are not functional in bacteria, suggesting
      further that the folding pathways are not the same in bacterial and in eukaryotic
      cells. This unpredictability of the bacterial system is unsettling and, only as
      more laboratories adopt this system because of its value for high-level P-450
      expression, will we learn more details of the requirements and limitations of
      this system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8131904
TI  - Polyclonal catalytic antibodies.

PMID- 8131905
TI  - Catalytic antibodies: the rerouting of chemical reactions.

PMID- 8131906
TI  - Production of catalytic antibodies using combinatorial libraries.

PMID- 8131907
TI  - Catalytic antibodies: designed and accidental.

PMID- 8131908
TI  - Catalytic antibodies for the hydrolysis of unactivated peptides.

PMID- 8131909
TI  - Interactions between co-existing beta-adrenoceptor subtypes in continuous cell
      lines.

PMID- 8131910
TI  - Coupling of histamine H1 and adenosine A1 receptors to phospholipase C in DDT1MF
      2 cells: synergistic interactions and regulation by cyclic AMP.
AB  - Intracellular cross-talk or synergism between receptors coupled negatively to
      adenylate cyclase via PTX-sensitive Gi-protein(s) and receptors coupled to
      phospholipase C via PTX-insensitive G-proteins is prevalent in a variety of cell
      types (see above) and may represent a universal mechanism for the modulation of
      phospholipase C activity (and hence calcium mobilization). However, the precise
      mechanism(s) involved in these synergistic interactions remain to be unravelled.
      In view of the recent findings by Camps et al. (1992), it may be that Gi-protein
      derived beta gamma subunits are responsible for the potentiation of phospholipase
      C activity observed in DDT1MF-2 cells (and other cell types). Clearly, the DDT1MF
      2 smooth muscle cell line appears to provide an ideal model system in which to
      investigate the mechanisms underlying the intracellular cross-talk between
      receptors coupled to PTX-sensitive and to PTX-insensitive G-proteins.

PMID- 8131911
TI  - Receptor-mediated intracellular signalling: oscillations and waves of cytosolic
      calcium.

PMID- 8131912
TI  - Conditional regulation of adenylyl cyclases by G-protein beta gamma-subunits.

PMID- 8131913
TI  - Second messenger and ionic modulation of agonist-stimulated phosphoinositide
      turnover in airway smooth muscle.

PMID- 8131914
TI  - Amplifying interactions between spasmogens in vascular smooth muscle.

PMID- 8131915
TI  - Errors in stop codon recognition in a temperature sensitive mutation of yeast.

PMID- 8131916
TI  - Pharmacokinetic behaviour of a deglycosylated t-PA mutant lacking the growth
      factor domain.

PMID- 8131917
TI  - EF-3: a novel fungal elongation factor with homology to E. coli ribosomal protein
      S5.

PMID- 8131918
TI  - Purification and characterisation of recombinant murine interleukin-5
      glycoprotein, from a Baculovirus expression system.

PMID- 8131919
TI  - Structure and mechanism of streptococcal protein G.

PMID- 8131920
TI  - Fc receptor mediated calcium signalling in differentiated and undifferentiated
      U937 cells.

PMID- 8131921
TI  - The interaction of IgG with Fc gamma RII: involvement of the lower hinge binding
      site as probed by NMR.

PMID- 8131922
TI  - Antigenicity of the Aeromonas salmonicida maltose-inducible outer membrane porin
      (maltoporin) and a hybrid protein derived from it.

PMID- 8131923
TI  - The energetics of prePhoE translocation.

PMID- 8131924
TI  - Construction and properties of Escherichia coli mutants defective in two genes
      encoding homologous membrane proteins with putative roles in anaerobic C4
      dicarboxylic acid transport.

PMID- 8131925
TI  - Evidence that the high affinity C4-dicarboxylate transport system of Rhodobacter
      capsulatus is a novel type of periplasmic permease.

PMID- 8131927
TI  - Stoichiometry of CO binding to the cytochrome bd complex of Azotobacter
      vinelandii.

PMID- 8131926
TI  - CO recombination as a probe of the Fe/Cu binuclear centre of terminal
      protonmotive oxidases.

PMID- 8131928
TI  - The effects of bicarbonate/carbon dioxide on the near-UV/visible spectrum and
      ligand binding properties of fast bovine heart cytochrome c oxidase.

PMID- 8131929
TI  - ATPase activity and ATP/ADP-induced conformational change in the bacterial toxin
      exporter hemolysin B.

PMID- 8131930
TI  - Inhibition of the Ca(2+)-ATPase by sesquiterpene lactones.

PMID- 8131931
TI  - Diacylglycerol kinase activity in intact small arteries.

PMID- 8131932
TI  - Fluctuations in 3H-choline-labelled metabolites in T-cell activation.

PMID- 8131933
TI  - Phospholipase D activation in PDGF-stimulated vascular smooth muscle cells.

PMID- 8131934
TI  - A novel phospholipase C inhibitor U73122, inhibits phospholipase C-independent
      processes in rat luteal cells.

PMID- 8131935
TI  - Protein kinase C activation of phospholipase D in C6 glioma cells.

PMID- 8131936
TI  - Mitogen-activated protein (MAP) kinase stimulation by phorbol esters and external
      load in the isolated perfused heart.

PMID- 8131937
TI  - Activation of MAP kinase in alpha T3-1 cells by luteinising hormone-releasing
      hormone.

PMID- 8131938
TI  - Characterisation of phosphatidylinositol 3-kinase in PC12 cell extracts and
      isolation of the enzyme from rat brain extracts.

PMID- 8131939
TI  - The intracellular distribution of inositol polyphosphates.

PMID- 8131940
TI  - Receptor derived phosphatidic acid is used in the biosynthetic pathway of
      phosphatidylinositol.

PMID- 8131941
TI  - Effects of pregnancy on agonist-stimulated PI hydrolysis in cardiomyocytes.

PMID- 8131942
TI  - Endothelin-1 stimulates inositol phosphate production in rat testis.

PMID- 8131943
TI  - Inhibition of inositol 1,3,4-trisphosphate 5/6-kinase by amino acid modifying
      agents.

PMID- 8131944
TI  - Partial purification of cell-signalling phosphatidic acid phosphohydrolase from
      rat liver.

PMID- 8131945
TI  - The temporal expression of cellular oncogenes in mechanically stimulated muscle.

PMID- 8131946
TI  - Aluminum stimulated c-fos gene expression in Swiss 3T3 fibroblasts.

PMID- 8131947
TI  - The effect of phosphatidic acid on the proliferation of Swiss 3T3 cells.

PMID- 8131948
TI  - Analysis of transcription factor activation in Swiss 3T3 fibroblasts.

PMID- 8131949
TI  - Identification of potential regulatory elements within the rat preprotachykinin A
      promoter.

PMID- 8131950
TI  - The pre-protachykinin A promoter interacts with a sequence specific single
      stranded DNA binding protein.

PMID- 8131951
TI  - Repair resistance of O6-methylguanine in DNA of hamster fibroblasts expressing a
      bacterial alkyltransferase gene is dependent on chromatin structure.

PMID- 8131952
TI  - Quantitation of HMG-CoA reductase mRNA levels in peripheral blood mononuclear
      cells of normal individuals and patients with altered lipoprotein metabolism.

PMID- 8131953
TI  - Mechanism of action of growth hormone in adipocytes: a role for protein kinase C?

PMID- 8131954
TI  - Unsaturated fatty acids inhibit lymphocyte protein kinase C activity.

PMID- 8131955
TI  - Identification of protein kinase C subspecies in wild-type and multidrug
      resistant cell lines.

PMID- 8131956
TI  - Detection of protein kinase C subspecies expression at the mRNA level using a
      reverse transcriptase-polymerase chain reaction approach.

PMID- 8131957
TI  - Effects of culture with unsaturated fatty acids on lymphocyte protein kinase
      activities.

PMID- 8131958
TI  - Staurosporine and its derivative RO31-8220, both inhibitors of protein kinase C,
      have different effects on C6 glioma cell morphology.

PMID- 8131959
TI  - Desensitisation of histamine H1 receptor-mediated calcium mobilisation in HeLa
      cells: the role of protein kinase C.

PMID- 8131960
TI  - The role of protein kinase C in TCR-induced interleukin-2 secretion in human
      Jurkat T cells.

PMID- 8131961
TI  - Definition of early Ca2+ signals induced by anti-CD3 antibody in a human Jurkat T
      cell line using a selective protein kinase C inhibitor, Ro 31-8425.

PMID- 8131962
TI  - Down-regulation of protein kinase C isotypes during postnatal development of rat
      heart.

PMID- 8131963
TI  - Biochemical characterisation of an apparently novel isoform of protein kinase C
      in pituitary.

PMID- 8131964
TI  - The effect of vanadate on selected mRNA abundance in streptozotocin-diabetic rat
      liver.

PMID- 8131965
TI  - Protein kinase C and the modulation of ATP-sensitive potassium channels in
      insulin-secreting cells.

PMID- 8131967
TI  - The effects of thiol modifiers on the activation of NF kappa B by interleukin-1.

PMID- 8131966
TI  - Evidence for a redox-sensitive protein tyrosine kinase in nuclear factor kappa B
      activation and interleukin 2 production in EL4.NOB1 cells.

PMID- 8131968
TI  - The activity of a phospholipase C beta assayed using phospholipid monolayers.

PMID- 8131969
TI  - Growth factor stimulated translocation of proteins into the nucleus in Swiss 3T3
      fibroblasts.

PMID- 8131970
TI  - Epidermal growth factor counteracts the insulin induced expression of glucokinase
      in hepatocytes.

PMID- 8131971
TI  - A novel urokinase receptor on monocyte-like macrophage cell line.

PMID- 8131972
TI  - The mitogen activated S6 kinase; sites of phosphorylation which lead to
      activation and identification of a putative kinase kinase.

PMID- 8131973
TI  - Increased phosphorylation of eukaryotic initiation factor 4 alpha during
      activation of T lymphocytes correlates with increased eIF-4F complex formation.

PMID- 8131974
TI  - Expression of PK-A catalytic subunit in mammary tissue during pregnancy and
      lactation.

PMID- 8131975
TI  - Surface-accessibility of the myristoylated N-terminus of PK-A catalytic subunit
      probed with anti-peptide antibodies.

PMID- 8131976
TI  - Inhibition of adipose tissue lipogenesis by growth hormone: role of polyamines.

PMID- 8131977
TI  - Association of solubilized bradykinin B2 receptors with G-proteins.

PMID- 8131978
TI  - Blockade of K+ channels in insulin-secreting cells by the 'potassium channel
      opener' SDZ PCO 400.

PMID- 8131979
TI  - Oestradiol-17 beta inhibits progesterone production by cultured human granulosa
      lutein cells in vitro.

PMID- 8131980
TI  - 15-Lipoxygenase induction as an index of oxidative stress and atherogenesis.

PMID- 8131981
TI  - Does nitric oxide mediate the inhibitory effects of bacterial endotoxin on
      hepatic gluconeogenesis?

PMID- 8131982
TI  - A low molecular weight (12-15kDa) protein fraction in rat liver binds alpha
      tocopherol.

PMID- 8131983
TI  - Regional saturation mutagenesis as an approach to identification of substrate
      specificity determinants in cytochrome P450 BM3.

PMID- 8131984
TI  - Glycosylation of yeast microsomal proteins: preliminary characterization studies.

PMID- 8131985
TI  - A novel inhibitor of cytochrome P450 BM3.

PMID- 8131986
TI  - Alkane metabolism by cytochrome P450 BM3.

PMID- 8131987
TI  - The interaction of biogenic amines with adrenal cytochrome P450-dependent
      enzymes.

PMID- 8131988
TI  - Antibody production to adrenal cytochrome P450-dependent enzymes using acid
      treated bacteria as immune carriers.

PMID- 8131989
TI  - New strategies for the generation of catalytic antibodies.

PMID- 8131990
TI  - The effect of 3 calmodulin antagonists on K(+)-stimulated neurotransmitter
      release from rat cortical slices.

PMID- 8131991
TI  - Cromoglycate selectively inhibits a rat liver microsomal lipid antioxidant system
      which is triggered by the cellular energy charge.

PMID- 8131992
TI  - Cromoglycate markedly activates ascorbate-ADP initiated lipid peroxidation in
      washed rat liver microsomes.

PMID- 8131993
TI  - Bradykinin-evoked release of [3H]noradrenaline from the human neuroblastoma SH
      SY5Y.

PMID- 8131994
TI  - Inhibition of platelet responses by N,N-diethyl-2[4
      (phenoxymethyl)phenoxy]ethanamine, HCl (DPPE) occurs through multiple mechanisms.

PMID- 8131995
TI  - Antiproliferative actions of cyclosporin A on endothelial cells are not exerted
      through protein kinase C (PkC).

PMID- 8131997
TI  - Activation of potassium channels by diazoxide and cromakalim in insulin-secreting
      cells is dependent upon internal ADP and channel run-down.

PMID- 8131996
TI  - Inositol phospholipid turnover in digitonin-permeabilised dispersed mouse
      pancreatic islet cells.

PMID- 8131998
TI  - Effects of 5-hydroxydecanoate on ATP-regulated potassium ion channels in insulin
      secreting cells.

PMID- 8131999
TI  - The involvement of protein kinase C in glucose-stimulated insulin secretion.

PMID- 8132000
TI  - Growth hormone decreases the amount of glucose transporter proteins in rat
      adipocyte plasma membranes.

PMID- 8132001
TI  - Modulation of cyclic AMP-dependent protein kinase activity by drugs affecting
      human platelet aggregation.

PMID- 8132002
TI  - Carbachol stimulated cAMP formation in SH-SY5Y cells is dependent on both
      extracellular and intracellular calcium.

PMID- 8132003
TI  - Growth hormone suppresses the expression of Gi2 in rat adipocytes.

PMID- 8132004
TI  - Regulation of membrane potential by G-protein-coupled receptors in L6 skeletal
      myocytes: the role of second messengers.

PMID- 8132005
TI  - Stimulation of chloride secretion and adenylate cyclase secretion in human
      colonic derived cell lines by calcitonin gene-related peptide.

PMID- 8132006
TI  - Annexins in porcine heart.

PMID- 8132007
TI  - Insulin-stimulated glucose uptake in C2C12 myoblasts.

PMID- 8132008
TI  - Insulin-like growth factor stimulation of inorganic phosphate transport into
      skeletal muscle.

PMID- 8132010
TI  - Control of intracellular creatine concentration in a mouse myoblast cell line.

PMID- 8132009
TI  - Modulation of inorganic phosphate uptake into a mouse myoblast cell line by
      extracellular creatine.

PMID- 8132011
TI  - Kinetics of phosphocreatine recovery in stimulated rat muscle in vivo.

PMID- 8132012
TI  - Effects of gut hormones on ovine adipose metabolism in vivo using microdialysis.

PMID- 8132013
TI  - Conformational changes in calpain II and its isolated subunits induced by AlCl3.

PMID- 8132014
TI  - Thermostability of the vanadium bromoperoxidase from Corallina officinalis.

PMID- 8132015
TI  - Effects of bile salts on enteropeptidase activity.

PMID- 8132016
TI  - Human liver bile acid sulphotransferase: characterisation of the partially
      purified enzyme.

PMID- 8132017
TI  - Comparison of the development of the liver microsomal glucose-6-phosphatase
      enzyme system in rat and guinea-pig.

PMID- 8132018
TI  - The purification and molecular weight determination of rat liver microsomal
      phospholipid N-methyltransferase.

PMID- 8132019
TI  - Blood glutathione and adenylates in acute pancreatitis.

PMID- 8132020
TI  - Dysregulation of T cell-macrophage network in severe acute pancreatitis.

PMID- 8132021
TI  - Suitability of B65 and SH-SY5Y neuroblastoma cells as models for 'in vitro'
      neurotoxicity testing.

PMID- 8132022
TI  - In vivo hepatic glucose disposal during pregnancy.

PMID- 8132023
TI  - Glycogenin: a new candidate gene for type II diabetes: metabolic and
      immunological markers in cultured human lymphoblasts.

PMID- 8132024
TI  - Isoprenaline-induced lipolysis in perfused mammary tissue.

PMID- 8132025
TI  - Inhibition of neutral cholesteryl ester hydrolase by a cytosolic protein in
      adipose tissue.

PMID- 8132026
TI  - The effect of cyclic AMP analogues on cholesterol metabolism in cultured rat
      hepatocytes.

PMID- 8132027
TI  - The utilisation of esterified and unesterified cholesterol derived from
      chylomicron remnants and high density lipoprotein for bile acid synthesis.

PMID- 8132028
TI  - Cultured human conjunctival cells secrete mucins.

PMID- 8132029
TI  - Inhibition of platelet aggregation and arachidonic acid metabolism by B-carboline
      alkaloids.

PMID- 8132030
TI  - Triterpenes and B-sitosterol from piper betle: isolation, antiplatelet and anti
      inflammatory effects.

PMID- 8132031
TI  - The effect of free radical scavengers on human enzymes involved with oxidation
      and reduction reactions.

PMID- 8132032
TI  - Structure probing of a highly methylated region in Xenopus laevis 28S ribosomal
      RNA.

PMID- 8132033
TI  - A gene probe to detect feline calicivirus from tissue samples.

PMID- 8132034
TI  - Differential steroid responsiveness of two estrogen regulated genes in MCF-7
      cells.

PMID- 8132035
TI  - Sodium stimulates ammoniagenesis in OK renal tubular epithelial cells.

PMID- 8132036
TI  - A dose-dependent enhancement of muscarinic activation of phospholipase C by
      halothane in SH-SY5Y cells.

PMID- 8132037
TI  - Characterization of the mu-opioid receptors on SH-SY5Y cells using beta
      funaltrexamine (beta-FNA) and naloxonazine.

PMID- 8132038
TI  - Analysis of polysulphate binding domains in boar proacrosin.

PMID- 8132039
TI  - Liver & kidney homogenates contain inhibitor(s) and activator(s) of the
      microsomal glucose-6-phosphatase system.

PMID- 8132040
TI  - The involvement of a cyclic nucleotide secondary messenger system in the
      prophenoloxidase cascade of the crustacean, Carcinus maenas.

PMID- 8132041
TI  - Changes in carotenoids with nitrogen stress in the cyanobacterium Synechococcus
      PCC6301.

PMID- 8132042
TI  - Dielectric properties of zwitterion solutions.

PMID- 8132043
TI  - Permittivity-variation and cell membrane research.

PMID- 8132044
TI  - Determination of 5'-nucleotidase activity in healthy and leukemic lymphocytes.

PMID- 8132045
TI  - A positron annihilation lifetime study of protein hydration.

PMID- 8132046
TI  - Regulation of sugar transport in chicken enterocytes.

PMID- 8132047
TI  - Evidence for polymorphism in mosquito esterases involved in insecticide
      resistance.

PMID- 8132048
TI  - Comparisons of nucleic acid sequences of esterases from resistant and susceptible
      strains of Culex quinquefasciatus.

PMID- 8132049
TI  - The function of esterases in insecticide resistance in Culex quinquefasciatus
      mosquitoes from Sri Lanka.

PMID- 8132050
TI  - Simultaneous real-time correlation of drug effects on dopamine efflux and uptake
      in rat striatal slices.

PMID- 8132051
TI  - Canine ocular mucins in health and dry eye disease.

PMID- 8132052
TI  - Application of breath pentane analysis to monitor age-related change in free
      radical activity.

PMID- 8132053
TI  - Purine nucleotide content in leukocytes from patients with B-chronic lymphocytic
      leukemia.

PMID- 8132054
TI  - Effect of streptozotocin-induced diabetes on magnesium inhibition of contractions
      of the rat uterus and G.I. tract.

PMID- 8132055
TI  - Purification of plasma membrane rat liver phosphatidylserine decarboxylase.

PMID- 8132056
TI  - Isozymes of rat brain myelin phospholipid-N-methyltransferase.

PMID- 8132057
TI  - The identification of several stearoyl-arachidonyl selective diacylglycerol
      kinases in the particulate fraction of porcine testes.

PMID- 8132058
TI  - Changes in the activities and cellular localisation of phospholipases in
      differentiating HL-60 cells.

PMID- 8132059
TI  - The regulation of agonist-stimulated phospholipase D activity in Swiss 3T3
      fibroblasts.

PMID- 8132061
TI  - Epidermal growth factor and insulin stimulate MAP kinase activity in cultured
      hepatocytes.

PMID- 8132060
TI  - A role for phospholipase D activation in B cell activation.

PMID- 8132062
TI  - Second messenger interactions in the rat adrenal cortex.

PMID- 8132063
TI  - The antigen receptors on B and T cells are not coupled to cytosolic phospholipase
      A2 activation and arachidonic acid release.

PMID- 8132064
TI  - Agonist activation of transfected human M1 muscarinic acetylcholine receptor in
      Chinese hamster ovary cells results in concurrent downregulation of Gq alpha and
      G11 alpha.

PMID- 8132065
TI  - Activation of the gonadotrophin releasing hormone receptor of alpha T3 cells
      results in downregulation of the alpha subunits of both Gq/G11.

PMID- 8132066
TI  - Lack of N terminal palmitoylation of G protein alpha subunits reduces membrane
      association.

PMID- 8132067
TI  - In vivo monitoring of respiratory chain dysfunction following renal storage and
      transplantation.

PMID- 8132068
TI  - Non-invasive monitoring of renal haemoglobin oxygenation kinetics following
      hypothermic storage and transplantation.

PMID- 8132069
TI  - Non invasive monitoring of tissue and haemoglobin oxygenation in the rabbit hind
      limb.

PMID- 8132070
TI  - Inhibition of carnitine palmitoyltransferase of the hepatic mitochondrial outer
      membrane (CPT-I) by 2-bromopalmitoyl-CoA.

PMID- 8132071
TI  - Effect of ethidium bromide on gene expression.

PMID- 8132072
TI  - Ciba Medal Lecture. Chromosomal abnormalities in cancer cells: identification of
      molecules important for tumour development.

PMID- 8132073
TI  - Ribosome frameshifting at hungry codons: sequence rules, directional specificity
      and possible relationship to mobile element behaviour.

PMID- 8132074
TI  - Probing the mechanism of ribosomal frameshifting on viral RNAs.

PMID- 8132075
TI  - Recognition of UGA as a selenocysteine codon in eukaryotes: a review of recent
      progress.

PMID- 8132076
TI  - Conserved features of selenoprotein P cDNA.

PMID- 8132077
TI  - Codon usage: mutational bias, translational selection, or both?

PMID- 8132078
TI  - Major codon preference: theme and variations.

PMID- 8132079
TI  - Codon context effects on nonsense suppression in human cells.

PMID- 8132080
TI  - Ternary complex-ribosome interaction: its influence on protein synthesis and on
      growth rate.

PMID- 8132081
TI  - Novel ribosome-associated translation factors are required to maintain the
      fidelity of translation in yeast.

PMID- 8132082
TI  - CII the Xenopus homologue of Saccharomyces cerevisiae SUP 45, which is encoded by
      a maternal RNA, is not essential for translational fidelity in egg extracts.

PMID- 8132083
TI  - Structure of G-protein-linked receptors.

PMID- 8132084
TI  - Phosphatidylcholine hydrolysis: a source of multiple lipid messenger molecules.

PMID- 8132085
TI  - Unclear or nuclear: another role for the phosphatidylinositol cycle?

PMID- 8132086
TI  - Nuclear localization of protein kinase C.

PMID- 8132087
TI  - Important roles for novel protein phosphatases dephosphorylating serine and
      threonine residues.

PMID- 8132088
TI  - Role of p21ras in growth factor signal transduction.

PMID- 8132089
TI  - Cytoplasmic to nuclear signal transduction by mitogen-activated protein kinase
      and 90 kDa ribosomal S6 kinase.

PMID- 8132090
TI  - p70s6k/p85s6k: mechanism of activation, effects of rapamycin and role in
      mitogenesis.

PMID- 8132091
TI  - Signalling to chromatin and the superinduction of proto-oncogenes.

PMID- 8132092
TI  - Nuclear response to cyclic AMP: central role of transcription factor CREM (cyclic
      AMP-responsive-element modulator).

PMID- 8132093
TI  - Organization of RNA polymerase II transcription and pre-mRNA splicing within the
      mammalian cell nucleus.

PMID- 8132094
TI  - Cyclins and their associated cyclin-dependent kinases in the human cell cycle.

PMID- 8132095
TI  - Control of nuclear factor-kappa B DNA-binding activity by inhibitory proteins
      containing ankyrin repeats.

PMID- 8132096
TI  - Transcription factor phosphorylation by the DNA-dependent protein kinase.

PMID- 8132097
TI  - Disruption of cell-cycle control by viral oncoproteins.

PMID- 8132098
TI  - DRTFI/E2F transcription factor: an integrator of cell-cycle events with the
      transcriptional apparatus.

PMID- 8132099
TI  - Three-dimensional structure and thermodynamics of antigen binding by anti
      lysozyme antibodies.

PMID- 8132100
TI  - Structural studies of CD4: crystal structure of domains 3 and 4 and their
      implication for the overall receptor structure.

PMID- 8132101
TI  - Modelling study of IgE/receptor interactions.

PMID- 8132102
TI  - Structural basis of the IgE-Fc epsilon RI interaction.

PMID- 8132103
TI  - Function of CD48 and its regulation by Epstein-Barr virus.

PMID- 8132104
TI  - Learning about photosystem II from analogies with purple photosynthetic bacteria.

PMID- 8132105
TI  - Comparative spectroscopy of photosystem II and purple bacterial reaction centres.

PMID- 8132106
TI  - Prokaryotic models for mitochondrial cytochrome c oxidase.

PMID- 8132107
TI  - Escherichia coli NADH dehydrogenase I, a minimal form of the mitochondrial
      complex I.

PMID- 8132108
TI  - Bladder and bowel.

PMID- 8132109
TI  - Evaluation of the Sonksen picture test for detection of minor visual problems in
      the surveillance of preschool children.
AB  - The Sonksen Picture Test (SPT) for surveillance of vision in preschool children
      was evaluated in 842 children, aged 21 to 60 months, from nine health districts
      in England, Wales and Scotland. The failures and controls were refracted and
      examined for squint; the Sheridan-Gardiner seven-letter chart (SGLC) was also
      used with children of > or = 42 months. The SPT was quicker to administer than
      the SGLC, with median times of one and five minutes, respectively. 98 per cent of
      children of all ages completed the SPT, whereas 10 per cent of those over 42
      months were unable to complete the SGLC. The test method that has been
      established is developmentally appropriate for this age-group, more so than
      optotype tests. It is a binocular test that is quick, cheap and simple to
      administer, and is available to children under five years.

PMID- 8132110
TI  - Auditory brainstem responses of children with developmental language disorders.
AB  - Brainstem auditory evoked potentials (BAEPs) were recorded from 48 children with
      language disorders (aged four to nine years old, IQs normal to borderline, normal
      audiometric thresholds and attending special school) and 20 healthy children
      (four to eight years old, with normal IQs, audiometry and school-level). The
      language-disabled group showed significantly lower absolute latency values of the
      BAEPs than controls. There were no significant differences in the central
      conduction time of the auditory pathway (I-V interval). Therefore, the only
      significant difference corresponded to a minor value for the first wave (auditory
      nerve discharge) of the BAEP. A reduction in the control mechanisms of the
      sensory inputs at the peripheral level, or a disturbance in the inhibitory
      mechanisms of cortico-subcortical modulation, might explain these findings.

PMID- 8132111
TI  - Relation between neonatal cranial ultrasound abnormalities and cerebral visual
      impairment in infancy.
AB  - A prospective follow-up study was conducted of a cohort of 65 at-risk neonates to
      assess the predictive value of neonatal cranial ultrasound abnormalities for
      cerebral visual impairment in infancy. Visual function was assessed using the
      acuity card procedure and behavioural visual responses were tested. Normal visual
      function was found in controls as well as in infants with small haemorrhages or
      mild leukomalacia. Infants with large haemorrhages performed poorly at 40 weeks
      postmenstrual age, but recovered to within the normal range in the first half
      year. In contrast, of the infants with extensive cystic leukomalacia, four of
      nine preterm infants and three of four term infants were severely visually
      impaired at 18 months. In the more mature infants, the cystic lesions extended
      deeper into the subcortical white matter, and this appeared to be associated with
      a worse visual outcome. Cystic leukomalacia proved to be highly predictive of
      cerebral visual impairment in infancy.

PMID- 8132112
TI  - Somatosensory evoked potentials following posterior tibial nerve stimulation
      predict later motor outcome.
AB  - Posterior tibial nerve somatosensory evoked potentials (PTN-SEPs) were performed
      on 50 neonates at high risk of future neurodevelopmental impairment just before
      their discharge from the neonatal intensive-care unit. The close association of
      sensory pathways with motor tracts and the need for sensory input and integration
      for normal motor functioning would indicate that CNS lesions producing motor
      deficits may be detected by this method. Follow-up of these infants revealed a
      highly significant relationship between bilaterally abnormal PTN-SEPs and the
      presence of cerebral palsy at three years of age. Normal PTN-SEPs were associated
      with a normal outcome in 24 of 25 infants. In this group of neonates, PTN-SEPs
      were more predictive than cranial ultrasound.

PMID- 8132113
TI  - A behavioural approach to retraining bowel function after long-standing
      constipation and faecal impaction in people with learning disabilities.
AB  - The authors describe a behavioural programme--involving prompted toilet-sitting
      after meals, rewards for appropriate evacuation and increased fibre--for four
      people with severe learning disabilities. Although treatment times were long,
      such training resulted in near-normal bowel function. While this behavioural
      approach does not ignore the biological aspects of the problem, soiling in
      intellectually disabled people should not be attributed to the handicapping
      condition alone. Training at an earlier age should be considered.

PMID- 8132114
TI  - Autistic behaviour and attention deficits in tuberous sclerosis: a population
      based study.
AB  - In a population-based sample of 28 individuals under the age of 20 years,
      autistic symptoms were present in 24 and DSM-III-R autistic disorder in 17. Many
      of the children and adolescents diagnosed as autistic also showed attention
      deficit/hyperactivity. There was no specific association between autistic
      behaviour and the presence of infantile spasms. Some of the children with
      tuberous sclerosis and autism were of near-normal intelligence. Indirectly, the
      results suggest that as many as 9 per cent of all children with autism may have
      tuberous sclerosis.

PMID- 8132115
TI  - Measuring right-hemisphere dysfunction in children: validity of two new computer
      tests.
AB  - The validity of two new computer-mediated tests for the detection of right
      cerebral hemisphere lesions in children--the Right-hemisphere Dysfunction Test
      and the Visual Perception Test--was evaluated. Normative data were drawn from a
      group of 91 children (aged five to 14 years) and 14 young adults. The tests were
      also administered to 14 children with acquired lesions of either right- or left
      cerebral hemisphere. The results demonstrate that the Right-hemisphere
      Dysfunction Test and the Visual Perception Test, with predictive values of 71 per
      cent and 88 per cent, respectively, are useful in clinical practice for detection
      of right-hemisphere dysfunction in children.

PMID- 8132116
TI  - How common is latex allergy? A survey of children with myelodysplasia.
AB  - To estimate the prevalence of latex allergy among children with myelodysplasia,
      describe the spectrum of associated clinical symptoms and evaluate potential risk
      factors for the development of latex sensitization, the authors conducted a
      survey at a regional spina bifida center. The findings suggest that symptomatic
      latex allergy is frequent among children with myelodysplasia and that those with
      a history of allergies and/or multiple surgical procedures are at greatest risk
      of sensitization. Until a sensitive and specific laboratory test for latex
      allergy is available, clinical history, especially allergy to balloons, may be an
      inexpensive and convenient way of identifying patients with myelodysplasia who
      may be at increased risk of more severe reactions and at whom preventive
      measures, such as reducing latex exposures and/or administration of prophylactic
      medications, should be targeted.

PMID- 8132117
TI  - Ring chromosome 20 mosaicism in a girl with complex partial seizures.
AB  - The authors report an 11-year-old girl with epilepsy, poor school-performance and
      minor behavioural disorders. The epilepsy is characterized by complex partial
      seizures, sometimes progressing secondarily into generalized tonic-clonic
      seizures, and is poorly controlled by medical treatment. Chromosomal analysis
      revealed a ring chromosome 20 mosaicism. The affected patient shows signs of ring
      chromosome 20 syndrome, characterized in the present case by poor school
      performance, behavioural disorders and epilepsy.

PMID- 8132118
TI  - Acquired stuttering after a second stroke in a two-year-old.
AB  - An almost two-year-old left-handed girl with a history of a left-hemisphere
      stroke at the age of one year developed a transient stutter with newly acquired
      white matter infarctions. Her course suggests that developmental stuttering may
      reflect anomalous dominance and/or atypical interhemispheric connectivity.

PMID- 8132119
TI  - The spasmodic upper-body squeeze: a characteristic behavior in Smith-Magenis
      syndrome.
AB  - The authors have observed a hand- and arm-squeezing behavior that seems to be
      highly characteristic of Smith-Magenis syndrome (SMS). This behavior serves as a
      useful diagnostic marker for SMS, a disorder in which the physical phenotype is
      often subtle. The squeezing behavior appears to be part of a complex upper-body
      tic which is exacerbated by happiness, excitement or overstimulation. The tic
      most often manifests as a 'self-hug', and is frequently associated with facial
      grimacing. Fleeting arm- and hand-squeezing movements may be repeated hundreds of
      times over the course of a day, but they do not significantly interfere with
      other hand functions. The excitable self-hugging in people with SMS may be one of
      the more benign and appealing aspects of their behavioral phenotype.

PMID- 8132120
TI  - The environmental basis of the Down syndrome phenotype.

PMID- 8132121
TI  - The effects of maternal epidural anaesthesia on neonatal behaviour during the
      first month.

PMID- 8132122
TI  - Assessment of spasticity in hemiplegic cerebral palsy. I. Proximal lower-limb
      reflex excitability.
AB  - The quadriceps and hamstring muscles of 13 children with hemiplegic cerebral
      palsy were studied using ramp and sinusoidal stretches at three different muscle
      lengths. Overall, the hamstring muscles showed greater velocity sensitivity than
      the quadriceps, with the hamstrings having the lowest reflex velocity and
      frequency thresholds close to maximum knee extension. At this position, the
      hemiparetic hamstrings alone showed a weakly significant reduced reflex frequency
      threshold compared with non-paretic muscles. For all other muscle lengths, non
      paretic and hemiparetic muscles displayed similar reflex thresholds when
      subjected to sudden, discontinuous or repetitive rhythmical, sinusoidal
      stretches. The number of muscles for which a reflex threshold could be
      established declined progressively as the angle at the knee joint approached 90
      degrees of flexion. Muscles for which no reflex threshold could be demonstrated
      had similar velocities and frequencies of stretch as those in which a reflex was
      obtained.

PMID- 8132123
TI  - Walking prognosis in cerebral palsy: a 22-year retrospective analysis.
AB  - A retrospective study was performed of 272 patients with spasticity to determine
      criteria for the prognosis for ambulation based on the ages at which children
      with cerebral palsy attain important gross motor milestones. The variables
      analysed were age at last clinical assessment, clinical type of cerebral palsy
      and ages at attainment of gross motor milestones. Achievement of head balance
      before nine months was an important parameter for good prognosis for walking and,
      after 20 months of age, an indicator for poor prognosis. Sitting by 24 months
      indicated a favourable outcome, and motor control of crawling at 30 months of age
      was a predictor for good prognosis. Based on these data, a chart for walking
      prognosis in children with cerebral palsy is presented.

PMID- 8132124
TI  - Clinical correlates of linear growth in children with cerebral palsy.
AB  - The purpose of this cross-sectional study was to determine correlates of linear
      growth in children with cerebral palsy (CP). 171 children with CP were measured
      and their charts reviewed. z scores were calculated for weight (Wz) and height
      (Hz). Hz correlated positively with Wz and head circumference, and negatively
      with age, the presence of spastic quadriplegia, non-ambulation and seizures. The
      correlation between Hz and age was stronger when non-ambulatory children were
      analysed separately. Multiple linear regression resulted in only Wz and age
      contributing significantly to the variance in stature as measured by Hz. These
      results provide preliminary evidence that nutritional status is a major correlate
      of growth in CP. The finding that linear growth worsens with age independent of
      nutrition suggests that other factors also influence growth in CP.

PMID- 8132125
TI  - Physiotherapy for clumsy children: an evaluation study.
AB  - This study reports the findings of an effect-evaluation study of physiotherapy
      for clumsy children. 18 children were identified by school doctors as having poor
      motor co-ordination. They were followed for three months in order to exclude
      spontaneous improvement of motor problems; none spontaneously improved.
      Subsequently, these children were enrolled on a regular physiotherapy programme.
      Treatment was administered individually twice a week over three months. The
      effects of treatment for clumsy children appeared to be promising: important
      improvements were found on various motor skills. These benefits were maintained
      for a three-month period after the end of treatment.

PMID- 8132126
TI  - Face recognition in children with early right or left brain damage.
AB  - Development of face processing after unilateral brain lesions sustained before
      one year of age was assessed in children aged between seven and 10 years by
      various tasks involving face processing. Each child was paired with an age- and
      IQ-matched control. There were three unilateral right-hemisphere lesions and
      three unilateral left lesions. The results showed that some of the skills
      relative to face processing were preserved (or recovered?), whereas other skills
      were severely impaired; the pattern varied from one child to another. The
      existence of these dissociations shows that preservation of low-level visual
      processing together with exposure to the appropriate stimuli for several years is
      by no means sufficient for face processing skills to develop normally.

PMID- 8132127
TI  - Hypothalamic hamartoma with skeletal malformations, gelastic epilepsy and
      precocious puberty.
AB  - A child is described who has skeletal malformations, gelastic epilepsy,
      precocious puberty and a hypothalamic hamartoma. The skeletal abnormalities were
      detected at birth, she developed gelastic epilepsy at the age of 3 years 5 months
      and precocious puberty at 3 years 8 months. A hypothalamic hamartoma was found on
      MRI. The precocious puberty has been successfully medically managed, though her
      seizures are difficult to control. The combination of all four features has not
      been described previously.

PMID- 8132128
TI  - Infantile chorea in an infant with severe bronchopulmonary dysplasia: an EMG
      study.
AB  - Recently a new movement disorder has been described which develops in some
      preterm infants with bronchopulmonary dysplasia. The present report provides a
      detailed description (including polyelectromyographical and serial cranial
      ultrasound findings) of this syndrome in a single infant. The authors suggest
      that the movement disorder be called infantile chorea, because the movement
      characteristics and EMG bursting pattern resemble those of adult chorea. It is
      hypothesized that 'infantile chorea', which is assumed to be caused by
      dysfunction of the striato-thalamic circuitry, emerges at the age of two to three
      months post-erm as thalamo-cortical connections are supposed to become
      functionally active.

PMID- 8132129
TI  - Electrical status epilepticus in childhood: neuropsychological impairment and
      therapeutic management.

PMID- 8132130
TI  - Does splenectomy predispose children to migraine?

PMID- 8132131
TI  - Paediatric neurology and paediatric neurologists.

PMID- 8132132
TI  - The treatment of sleep disorders with melatonin.
AB  - Fifteen children (most of whom were neurologically multiply disabled) with
      severe, chronic sleep disorders were treated with 2 to 10mg of oral melatonin,
      given at bedtime. Nine had fragmented sleep patterns, three had delayed sleep
      onset and three others had non-specific sleep disturbance of unclear aetiology;
      all had failed to respond to conventional management. Nine patients had ocular or
      cortical visual impairment. The health, behavioural and social benefits of
      treatment were significant, and there were no adverse side-effects. While the
      response was not always complete, the study clearly showed that melatonin has an
      important role in the treatment of certain types of chronic sleep disorders.

PMID- 8132133
TI  - Inhibition of pancreatic secretion under long-term octreotide treatment in
      humans.
AB  - The somatostatin analogue octreotide (SMS 201-995) is a potent inhibitor of human
      exocrine pancreatic secretion. In the present study we analyzed the effect of
      octreotide (3 x 100 micrograms, daily) given over a time period of 7 days on
      hormone-stimulated exocrine pancreatic secretion in 6 healthy volunteers using a
      secretin-ceruletide test. The secretin-ceruletide test was carried out before,
      following the first injection of octreotide (day 1) and after a 7-day treatment
      with 3 x 100 micrograms octreotide daily. Duodenal fluid was collected over 30
      min without stimulation, over 60 min following a bolus injection of 1 U/kg body
      weight secretin, and over 60 min during a continuous infusion of secretin and
      ceruletide. Following the first injection of octreotide and following 7 days of
      octreotide treatment secretin/ceruletide-stimulated amylase secretion was
      significantly reduced. Trypsin and chymotrypsin secretion was significantly
      reduced after the first injection of octreotide when pancreatic secretion was
      stimulated by secretin and ceruletide simultaneously. However, secretin and
      ceruletide-induced trypsin and chymotrypsin secretion was not inhibited after 7
      days of octreotide treatment. Baseline, secretin and secretin/ceruletide
      stimulated bicarbonate output were not influenced by octreotide either following
      the first injection of octreotide or the 7 days' treatment. Octreotide is a
      potent inhibitor of secretin/ceruletide-stimulated pancreatic amylase, trypsin
      and chymotrypsin secretion. However, following a 7-day treatment with octreotide
      this inhibition is only persistent for pancreatic amylase secretion.

PMID- 8132134
TI  - Octreotide in the treatment of acute pancreatitis: results of a unicenter
      prospective trial with three different octreotide dosages.
AB  - Acute necrotizing pancreatitis is still associated with high morbidity and
      mortality. In this prospective clinical trial, we analyzed the effect of
      octreotide in patients with acute pancreatitis. Eight patients received either 3
      x 100, 3 x 200 or 3 x 500 micrograms octreotide subcutaneously per day over a
      period of 10 days. The complication rate was lower in the group of patients who
      received 3 x 200 or 3 x 500 micrograms octreotide than in the control group and
      the group of patients who received the dosis of 3 x 100 micrograms octreotide per
      day. The results of this study are promising and must be validated in a
      controlled clinical trial with octreotide in a larger patient population.

PMID- 8132135
TI  - Prophylaxis of complications after pancreatic surgery: results of a multicenter
      trial in Germany.
AB  - Major pancreatic resection still carries a considerable risk for morbidity and
      even mortality. Complications occurring after pancreatic surgery are chiefly
      linked with exocrine pancreatic secretion. Therefore to inhibit exocrine
      pancreatic secretion perioperatively seems to be a promising concept in the
      prevention of complications following pancreatic resection. The hormone
      somatostatin and its synthetic analogue octreotide have been demonstrated to
      inhibit exocrine pancreatic secretion profoundly, particularly the secretion of
      proteases is decreased. In a randomized placebo-controlled multicentric and
      double-blind trial we analyzed the role of octreotide in the prevention of post
      operative complications after major pancreatic surgery. A significant reduction
      of complications (fistula, abscess, fluid collection, sepsis, pulmonary
      insufficiency, postoperative acute pancreatitis) could be demonstrated in
      patients receiving octreotide (3 x 100 micrograms/day s.c.). The effect of
      octreotide was particularly true in patients undergoing a Whipple resection for
      cancer.

PMID- 8132136
TI  - Prophylaxis of complications after pancreatic surgery: results of a multicenter
      trial in Italy. Italian Study Group.
AB  - An Italian prospective multicentre study evaluated the efficacy of octreotide, a
      synthetic somatostatin analogue, in preventing the complications of elective
      pancreatic surgery. 303 patients with tumours of the pancreas or the ampullary
      region, in whom ultrasonography and computed tomography scan had shown a
      resectable lesion, or with chronic pancreatitis, were randomized in a double
      blind fashion to treatment with octreotide 100 micrograms t.i.d. s.c. starting at
      least 1 h before surgery and continued till the 7th postsurgical day, or with
      matching placebo. Unresectable lesions were found at laparatomy in 31 patients
      (15% of those with tumours). In 14 others, procedures not anticipated in the
      study protocol had to be performed, and in 6 additional cases there were other
      protocol violations so that these 20 patients were excluded from the study
      analysis. Considering the 252 evaluable patients, the complication rate was
      significantly higher in the 130 placebo-treated patients than in the 122 who
      received octreotide (29.2 vs. 15.6%; p = 0.01). We therefore suggest that
      octreotide may substantially reduce the risk of complications after elective
      pancreatic surgery.

PMID- 8132137
TI  - Role of octreotide in the treatment of pancreatic cancer.
AB  - Prognosis in patients with advanced pancreatic cancer is dismal. There has been
      no effective therapy for these patients so far. Somatostatin and its analogues
      have been proven to be potent inhibitors of experimental pancreatic cancer. Tumor
      inhibition is supposed to be mediated directly by somatostatin-binding sites or
      indirectly by suppression of growth factors. In two trials the value of the new
      somatostatin analogue octreotide in a low-dose (3 x 100 micrograms/day) and a
      high-dose (3 x 2,000 micrograms/day) protocol was evaluated in patients with
      advanced pancreatic cancer. Median survival of the patients with a low-dose
      protocol was 3 months. However, the treatment of pancreatic cancer with a high
      dose protocol revealed a median survival of 6 months and stable disease in 4/10
      patients. According to quality of life scoring 4 patients showed values
      comparable to healthy controls. Octreotide therapy with a high-dose protocol is a
      promising experimental therapeutic approach to advanced pancreatic cancer.

PMID- 8132138
TI  - Computerized student testing as a learning tool in a family practice clerkship.
AB  - BACKGROUND: The purpose of this paper is to describe and evaluate a computerized
      multiple choice testing system developed to teach family medicine core content in
      a junior clerkship. METHODS: Students were tested in a minimum of 10 content
      areas based upon a pretest, and answered sets of 10 randomly generated questions
      in each area. Students received immediate feedback on scores and correct answers.
      RESULTS: A total of 192 students took 10,184 computerized tests. Mean student
      scores rose significantly with successive tests. Scores on the written final
      clerkship examination correlated with computerized testing scores. Students
      accepted the computerized testing system well. CONCLUSIONS: The computerized
      testing system led to immediate learning, but its effects on long-term learning
      were less clear.

PMID- 8132139
TI  - Computerized performance support systems: applications in a family practice
      clerkship.
AB  - This article describes a computerized performance support system, the Clerkship
      Learning Expert and Resource Consultant (CLERC), developed to improve the quality
      and consistency of learning available to medical students in a third-year family
      practice clerkship. CLERC is an integrated computer system with an interactive
      knowledge base, software applications, literature search capabilities, and
      clinical diagnostic software programs. Medical students enrolled in a third-year
      family practice clerkship use CLERC to access up-to-date clinical information and
      to complete clerkship assignments.

PMID- 8132140
TI  - Measuring self-reported comfort with general family practice skills during a
      required third-year family practice clerkship.
AB  - BACKGROUND: To judge the effectiveness of a new required third-year family
      practice (FP) clerkship, we designed a 20-item FP comfort assessment (FPCA) to
      measure students' self-reported comfort with a wide range of FP skills. This
      report examines the behavior and characteristics of the FPCA. METHODS: During the
      1990-91 academic year, 179 students who completed the FP clerkship were asked to
      complete the FPCA on the first and last days of the clerkship. RESULTS: Factor
      analysis of responses yielded four factors that explained 66.4% of the total
      variance: relationships and values, history and physical, diagnosis and
      management, and preventive medicine. After adjustment, internal consistency for
      each factor ranged from .77 to .89. All postclerkship factor scores were
      significantly greater than preclerkship factor scores, indicating that the FPCA
      performed as expected. All postclerkship factor scores and two of the change
      scores correlated significantly with the students' overall clerkship grade,
      indicating concurrent validity. CONCLUSION: The FPCA is a reliable and valid
      measure of student comfort with patient-centered FP skills.

PMID- 8132141
TI  - Defensive behavior of Dutch family physicians. Widening the concept.
AB  - Defensive medicine is commonly defined as "deviations, induced by a threat of
      liability, from what the physician believes is, and what is generally regarded as
      sound medical practice." Although, generally speaking, there is much concern
      about its prevalence and its consequences for American health care, some authors
      argue that much of what is passed off as defensive medicine has little to do with
      fear of lawsuits, because defensive medicine also occurs in countries where
      malpractice litigation is rare. Studies done in The Netherlands, where there is
      very little malpractice litigation, indicate that a desire to prevent problems in
      the doctor-patient relationship is a major cause of defensive behavior by family
      physicians. We suggest that a wider conceptualization of defensive medicine may
      improve our understanding of the American situation.

PMID- 8132142
TI  - Colposcopy and cervical biopsy educational training models.
AB  - BACKGROUND: Realistic simulation models serve meaningful educational purposes.
      The intent of this article is to review the physical and educational features of
      three instructional colposcopy models, and to discuss the advantages and
      implications of the use of models in teaching colposcopic skills. METHODS: Models
      made from latex, steak, and the bovine cervix were assessed as instructional
      devices to simulate the uterine cervix and cervical disease. Model construction,
      preparation, and unique features were critiqued. The models were also evaluated
      for their potential use in the preclinical teaching of important colposcopic
      skills. RESULTS: The latex model required minimal assembly but was costly. It was
      limited in design, which would exclude the training of most colposcopic
      techniques. The steak model used readily available materials, facilitated
      colposcopic skill acquisition, and was the least expensive model. The bovine
      model best simulated human cervical tissue, was intermediate in cost, and enabled
      teaching a variety of colposcopic procedures. The optional silicone inserts
      realistically demonstrated the spectrum of cervical disease. CONCLUSIONS: Various
      cervical biopsy models have different strengths and weaknesses for teaching
      colposcopic procedural skills. Available models each possess unique features
      designed to reproduce anatomy, pathology, tissue texture, and technical spatial
      limitations. The models permit assessment of gynecologic knowledge and
      psychomotor abilities.

PMID- 8132143
TI  - Defensive medicine: it may not be what you think.

PMID- 8132144
TI  - The starship family practice.

PMID- 8132145
TI  - Do patients understand medical talk?

PMID- 8132146
TI  - Teaching residents circumcision.

PMID- 8132147
TI  - Use of the OSCE in residency training.

PMID- 8132148
TI  - Determination of 16S ribosomal RNA sequences of all members of the genus
      Peptostreptococcus and their phylogenetic position.
AB  - A comparative analysis of 16S ribosomal RNA sequences of all Peptostreptococcus
      species revealed that most members of the genus Peptostreptococcus should be
      divided into many different genera. The relationship between clostridia and
      peptostreptococci was analysed to find the phylogenetic position of
      peptostreptococci.

PMID- 8132149
TI  - Membrane-associated hemolysin activities in mycoplasmas.
AB  - Mycoplasmas are cell wall-less organisms that require membrane precursors for
      growth. Activities involved in the acquisition of these materials have been
      hypothesized as mycoplasmal virulence factors because of the effects these
      activities might have on host cells. Twenty-nine species or strains of
      mycoplasmas were examined for membrane-associated hemolysis activity similar to
      that previously identified in Mycoplasma pulmonis. Membrane-associated hemolytic
      activity was found in most mycoplasma species, but the amount of activity varied
      between and within the species. All of the arginine-utilizing mycoplasmal
      species, one M. pulmonis strain, one Acholeplasma species, and the intracellular
      human pathogens M. penetrans and M. fermentans ssp. incognitus were devoid of
      activity. The wide distribution of the membrane-associated hemolysis activity
      suggests that it may be important to the survival of the organism.

PMID- 8132150
TI  - Inactivation of the streptokinase gene prevents Streptococcus equisimilis H46A
      from acquiring cell-associated plasmin activity in the presence of plasminogen.
AB  - The streptokinase gene of Streptococcus equisimilis H46 was inactivated by
      plasmid insertion mutagenesis to study the relationship between elaboration of
      streptokinase and acquisition of cell-associated plasmin activity after
      incubation of wild-type and mutant cells in media containing plasminogen or
      plasmin. The results showed that H46A binds both the zymogen and active enzyme,
      generates surface-associated plasmin activity in the presence of plasminogen when
      producing streptokinase, and expresses its plasmin(ogen) receptor(s)
      independently of a functional streptokinase gene. At least part of the
      plasmin(ogen) binding capacity may be due to the glyceraldehyde-3-phosphate
      dehydrogenase type of receptor molecule, as judged by the detection of the
      corresponding gene.

PMID- 8132151
TI  - Regulation of spvR, the positive regulatory gene of Salmonella plasmid virulence
      genes.
AB  - The regulation of the spvR promoter from the Salmonella dublin virulence plasmid
      was monitored using promoter-reporter gene fusion constructs. Activity was
      dependent upon the presence of the spv region and was affected by the number of
      copies of the spv region present within the cell. Activity remained constant
      throughout exponential growth, and increased rapidly with the onset of stationary
      phase, under both aerobic and anaerobic conditions. Additionally, the level of
      spvR expression was controlled by the availability of iron, activity being
      greatest under low iron conditions in stationary phase. The spvA gene product
      negatively regulated spvR expression in a dose-dependent manner, indicating that
      SpvA provides a negative feedback mechanism for this operon.

PMID- 8132152
TI  - Klebsiella oxytoca: resistance to aztreonam by overproduction of the
      chromosomally encoded beta-lactamase.
AB  - Aztreonam-resistant Klebsiella oxytoca strain SL7811 was selected on agar
      containing 1 microgram of aztreonam per ml from a susceptible strain SL781. The
      MICs for the resistant mutant towards penicillins, aztreonam and ceftriaxone were
      much higher, to cefotaxime slightly higher and to ceftazidime unchanged.
      Synthesis of beta-lactamase was 223-fold greater in the mutant compared with the
      susceptible strain. SL781 and its resistant mutant SL7811 produced beta-lactamase
      with the same isoelectric point and substrate profile. The beta-lactamase genes
      from SL781 and SL7811 were cloned in plasmid pBGS18 giving pBOF-1 and pBOF-4
      respectively. The sequences of the two putative promoters indicated two
      modifications in the resistant plasmid pBOF-4: a transversion (G-->T) in the
      first base of the -10 consensus sequence and a deletion of one C residue four
      base pairs upstream of the -10 hexamer.

PMID- 8132153
TI  - Rescue by vitamin B12 of Escherichia coli cells treated with colicins A and E
      allows measurement of the kinetics of colicin binding on BtuB.
AB  - Sensitivity of Escherichia coli bacteria to colicins A and E1 was significantly
      increased by overproduction of the BtuB receptor protein. The amount of vitamin
      B12 needed before colicins A and E1 treatment to protect cells against killing
      was found to be a function of the number of BtuB molecules present at the cell
      surface. Cells treated by colicins A and E were rescued from killing by addition
      of vitamin B12 shortly after colicin treatment. The rate of reversal by vitamin
      B12 may correspond to the kinetics of irreversible binding to BtuB of the various
      colicins.

PMID- 8132154
TI  - Amplification and nucleotide sequence of the quinolone resistance-determining
      region in the gyrA gene of mycobacteria.
AB  - Chromosomal DNA of different species of mycobacteria, Mycobacterium tuberculosis,
      Mycobacterium leprae, Mycobacterium avium and Mycobacterium smegmatis, has been
      submitted to polymerase chain reaction using two oligonucleotide primers highly
      homologous to DNA sequences flanking the quinolone resistance-determining region
      in the gyrA gene of Escherichia coli and Staphylococcus aureus. For each of these
      mycobacterial species, a 150-bp DNA fragment hybridizing with an intragenic probe
      of the gyrA gene of E. coli K12 was obtained. The nucleotide sequences of the 108
      bp fragments amplified from M. tuberculosis and M. avium were determined. The two
      sequences were 87% homologous. Except for one residue, their deduced amino acid
      sequences were identical and shared 67% homology with the quinolone resistance
      determining region of the gyrase A subunits of E. coli and S. aureus. Sequencing
      of the 108-bp fragment amplified from an in vitro mutant of M. avium, highly
      resistant to fluoroquinolones, showed a point mutation leading to the
      substitution of Ala for Val at a position corresponding to residues involved in
      quinolone resistance in E. coli and S. aureus, i.e. Ser 83 for E. coli and Ser 84
      for S. aureus.

PMID- 8132155
TI  - Occurrence and expression of cspA, a cold shock gene, in Antarctic psychrotrophic
      bacteria.
AB  - The homologue of cold shock gene cspA of Escherichia coli was detected in various
      isolates of Antarctic psychrotrophs representing both Gram-positive and Gram
      negative bacteria. The Northern hybridization study indicated that the transcript
      size of cspA in the psychrotrophic Gram-positive bacterium Arthrobacter
      protophormiae and Gram-negative Pseudomonas fluorescens was similar to that of E.
      coli and that the cspA homologues in these two psychrotrophs were expressed
      constitutively at a low level both at 4 degrees C and 22 degrees C. In P.
      fluorescens, the expression of cspA mRNA was inducible after shift of temperature
      from 22 to 4 degrees C and the maximum level of induction occurred after 1 h
      which correlated with the time-lag required for growth of the culture after
      temperature shift.

PMID- 8132156
TI  - Characterization of translucent segments observed in an smbA mutant of
      Escherichia coli.
AB  - The smbA gene of Escherichia coli is essential for cell proliferation. The smbA2
      mutant shows cold-sensitive colony formation at 22 degrees C. A novel
      morphological phenotype, formation of a translucent segment at midcell or at a
      cell pole, was observed by phase-contrast microscopy at a high frequency in the
      smbA2 mutant cells incubated in L medium lacking NaCl at 22 degrees C, but not
      observed in L medium containing 1% NaCl or 20% sucrose at the same temperature.
      No translucent segment was observed in the wild-type cells in any of the media
      used. Electron microscopic observation revealed that the translucent segments
      resulted from the enlargement of a periplasmic space by separation of the inner
      membrane from the peptidoglycan layer and the outer membrane.

PMID- 8132157
TI  - Metabolism of 4-chlorophenol by Azotobacter sp. GP1: structure of the meta
      cleavage product of 4-chlorocatechol.
AB  - A mutant strain of Azotobacter sp. GP1 converted 4-chlorophenol to 4
      chlorocatechol under cometabolic conditions. Under the same conditions the wild
      type strain accumulated a yellow compound, which by chemical and spectroscopic
      methods was identified as 5-chloro-2-hydroxy-6-oxohexadienoic acid (5-chloro-2
      hydroxy-muconic semialdehyde). The structure of this compound indicates a meta
      proximal cleavage of 4-chlorocatechol.

PMID- 8132158
TI  - Cloning and sequence analysis of the gene encoding Lactococcus lactis malolactic
      enzyme: relationships with malic enzymes.
AB  - Malolactic enzyme is the key enzyme in the degradation of L-malic acid by lactic
      acid bacteria. Using degenerated primers designed from the first 20 N-terminal
      amino acid sequence of lactococcal malolactic enzyme, a 60-bp DNA fragment
      containing part of the mleS gene was amplified from Lactococcus lactis in a
      polymerase chain reaction. This specific probe was used to isolate two contiguous
      fragments covering the gene as a whole. The 1.9-kb region sequenced contains an
      open reading frame of 1623 bp, coding a putative protein of 540 amino acids. The
      deduced amino acid sequence reveals that lactococcal putative protein (Mlep) is
      highly homologous to the malic enzyme of other organisms. Expression of the mleS
      gene in Escherichia coli results in malolactic activity.

PMID- 8132159
TI  - An assessment of the dietary uptake of di-2-(ethylhexyl) adipate (DEHA) in a
      limited population study.
AB  - The plasticizer di-2-(ethylhexyl) adipate (DEHA), which may be present in food
      contact films, can migrate into certain foodstuffs. Results from plasticizer
      migration studies into food have enabled an indirect estimate of the maximum
      daily dietary intake of DEHA. A previous study of the metabolism and
      pharmacokinetics of DEHA in humans identified the urinary metabolite 2
      ethylhexanoic acid (EHA) as a useful marker metabolite for assessing DEHA intake.
      The present study was designed to investigate urinary EHA concentrations
      following a controlled dose of DEHA presented with food, and to assess the
      average daily intake of DEHA in a limited population survey. The urinary
      elimination profile of EHA, following a dose of DEHA in food, showed that in
      order to extrapolate DEHA intake from EHA measurements, a 24-hr urine sample was
      required. In the survey the elimination of EHA was determined in 24-hr urine
      samples in 112 individuals from five different geographical locations in the UK.
      No restrictions were placed on age or gender. Estimates of daily intake of DEHA
      show a skewed distribution with a median value of 2.7 mg. This is similar to an
      estimated maximum daily intake of 8.2 mg/day, derived using an indirect method by
      the UK Ministry of Agriculture, Fisheries and Food.

PMID- 8132160
TI  - Characterization of mutagenic activity in cooked-grain-food products.
AB  - Wheat gluten or flour from several plant sources heated at 210 degrees C for 1 hr
      produced 0-1800 revertant colonies/g in the Ames/Salmonella test using strain
      TA98 with metabolic activation. Baked or toasted foods and a heated grain
      beverage showed a mutagenic response in all cases from 2 to 320 revertants/g,
      with higher values seen when overcooked. Fried meat-substitute patties showed 0
      23 revertants/g when fried at 210 degrees C. A greater mutagenic response in
      bacterial strain TA98 than in strain TA100 and a requirement for metabolic
      activation suggests that one or more aromatic amine mutagens are formed at normal
      cooking temperatures, but the mutagenic activity measured cannot be accounted for
      by the known heterocyclic amines commonly found in cooked meats. We conclude that
      grain products from aromatic amine chemicals during heating that are mutagenic in
      bacterial mutation tests.

PMID- 8132161
TI  - Determination of the mycotoxin fumonisin B1 and identification of its partially
      hydrolysed metabolites in the faeces of non-human primates.
AB  - A method has been developed for the determination of fumonisin B1 (FB1) in the
      faeces of non-human primates (vervet monkeys). The animals were dosed with 14C
      labelled FB1, and the radioactive compounds in faeces were recovered by repeated
      extractions with 0.1 M ethylenediaminetetraacetic acid. The extracts were cleaned
      up on a reversed-phase (C18) solid-phase extraction cartridge, and FB1 was
      determined by o-phthaldialdehyde derivatization and reversed-phase HPLC. The
      analytical method for the determination of FB1 in the faecal extracts was
      reproducible [2.6% relative standard deviation (RSD)] and accurate (recovery from
      spiked blank extracts of 93 +/- 2.9% RSD). Confirmation of the identification of
      FB1 in faeces was achieved using HPLC and thin-layer chromatography, which showed
      that the radioactivity extracted corresponded mainly to FB1 and a new metabolite
      with chromatographic properties similar to those of the mycotoxin. The new
      metabolite was identified by mass spectrometry and nuclear magnetic resonance
      spectroscopy to be an equilibrium mixture of the two structural isomers of
      partially hydrolysed FB1, which are formed by hydrolysis of one of the ester
      groups of the mycotoxin.

PMID- 8132162
TI  - Direct detection using the Drosophila DNA-repair test and isolation of a DNA
      damaging mycotoxin, 5,6-dihydropenicillic acid, in fungal culture.
AB  - The Drosophila DNA-repair test was used in an attempt to detect fungal production
      of DNA-damaging mycotoxins without an extraction process. 29 species of fungi, 13
      Aspergillus, 12 Penicillium and four Fusarium were inoculated directly to a
      Drosophila medium, and the larvae were then bred in the mouldy medium. Production
      of DNA-damaging mycotoxin was detected directly by counting the decrease in the
      survival of DNA-repair-deficient flies. With the direct detection method,
      Aspergillus ochraceus, A. parasiticus and A. versicolor produced DNA-damaging
      mycotoxins. The same results were obtained with the mouldy medium extract using
      the standard DNA-repair test. The direct detection method was convenient for
      surveying the fungal production of DNA-damaging mycotoxins. The extracts of A.
      parasiticus and A. versicolor contained aflatoxin B1 and sterigmatocystin,
      respectively. The DNA-damaging compound in the extract of A. ochraceus was
      isolated and purified to clear, colourless 'needles'. With nuclear magnetic
      resonance-mass spectroscopy spectra, the compound was confirmed to be 5,6
      dihydropenicillic acid, the DNA-damaging potency of which has not been previously
      reported.

PMID- 8132163
TI  - Acute toxicity of ganciclovir: effect of dietary restriction and chronobiology.
AB  - The effect of diet, age and time of dose delivery on the mortality of female
      B6C3F1 mice from ganciclovir sodium (DHPG) was determined for both single (SD;
      400 mg DHPG/kg, ip) and multiple doses (MD; same dose ip for 10 additional days)
      of the drug. Young (7-10 months) and middle-aged (MA; 19-22 months) mice
      (B6C3F1), both fed ad lib. (AL) and calorie restricted (CR), were dosed at 0, 6,
      12 and 18 hr after lights on (HALO; SD study) and at 12.00 hr (MD study). The SD
      study mortality rate was 38% (AL) and 1.7% (CR) (P < 0.00001). Mortality was 53%
      (AL, young; P < 0.00001), over 20% (AL, MA), over 1.8% (CR, MA; P = 0.00004) or
      more than 1.7% (CR, young; P = 0.00002). Effects were independent of lean body
      mass differences between AL and CR mice. In the SD study, comparing AL mice only,
      the greatest mortality was seen in young mice at 6 HALO, (73%; P = 0.0034) and
      lowest mortality in MA mice at 12 HALO (8%; P = 0.026), whereas in the MD study
      mortality was 63% AL and 33% CR (P = 0.015). By age, MD mortality was 80% (AL,
      young; P = 0.0035), 50% (CR, MA), 47% (AL, MA), and 15% (CR, young; P = 0.0013).
      CR protected both young and MA mice in SD and young mice in MD. Lowest mortality
      for AL was at 12 HALO. It is suggested that dosing at 12 HALO may protect by
      decreasing DHPG uptake during a period of minimal DNA synthesis in the affected
      organ(s). CR and timing of DHPG dose may obviate the necessity to discontinue
      DHPG because of toxicity in humans. The most significant finding of this study is
      the impact of diet on mortality.

PMID- 8132164
TI  - Human in vivo percutaneous absorption of pyrethrin and piperonyl butoxide.
AB  - In order to determine the human in vivo percutaneous absorption of pyrethrin and
      piperonyl butoxide, a commercial formulation containing either [14C]pyrethrin
      (3.8 mCi/mmol) or [14C]piperonyl butoxide (3.4 mCi/mmol) was applied to the
      ventral forearm of six human volunteers. The formulation contained 0.3% pyrethrin
      and 3.0% piperonyl butoxide. Spreadability studies showed that concentrations of
      5.5 micrograms pyrethrin/cm2 and 75.8 micrograms piperonyl butoxide/cm2 (used in
      this study) would be consistent with levels found in actual use. The forearms
      were thoroughly cleansed with soap and water 30 min after application (as
      recommended for actual use). Percutaneous absorption was determined by urinary
      cumulative excretion following dose application. With a 7-day urinary
      accumulation, 1.9 +/- 1.2% (SD) of the dose of pyrethrin and 2.1 +/- 0.6% of the
      dose of piperonyl butoxide applied was absorbed through the forearm skin. 1 hr
      after application blood samples contained no detectable radioactivity. The
      percutaneous absorption of pyrethrin and piperonyl butoxide from the scalp was
      calculated to be 7.5% of the applied dose for pyrethrin and 8.3% for piperonyl
      butoxide. The calculated half-life of 14C excretion was 50 hr for pyrethrin and
      32 hr for piperonyl butoxide. The data should be of relevance to appropriate risk
      assessment in extrapolating animal data to humans.

PMID- 8132165
TI  - Formation of mutagenic activity from amino acids heated at cooking temperatures.
AB  - To investigate the formation of aromatic amine-like mutagenic activity in cooked
      grain foods, amino acids were heated alone or in binary combinations at either
      150 or 210 degrees C. About half of the binary mixtures of arginine heated with
      other amino acids produced potent mutagenic responses in the Ames/Salmonella
      assay, but only cysteine produced mutagenic products when heated alone. One-to
      one molar ratios of arginine heated with threonine, valine, cystine, cysteine or
      tryptophan produced reaction products that gave 1200-3200 revertants/mmol in
      Salmonella strain TA98 with metabolic activation. 1-Methylguanidine, a fragment
      of arginine, produced a mutagenic response when heated alone or in binary
      mixtures with all amino acids tested. Analysis of reaction product extracts by
      solid-phase extraction and HPLC failed to find the known heterocyclic amines
      commonly found in cooked meats that would explain the measured mutagenic
      activity. As judged by biological and chemical characterization, several new
      aromatic amine mutagens are formed by heating some simple amino acids combined
      with arginine, and these reactants may be the source of the mutagenic products
      detected in the extracts of some cooked grain-based foods.

PMID- 8132166
TI  - Aflatoxin contamination of Nigerian foods and feedingstuffs.
AB  - Human foods and animal feeds, and ingredients used for their preparation or
      formulation in Nigeria, were surveyed between 1988 and 1991 for the presence of
      the fungal metabolite and animal carcinogen aflatoxin. Groundnut and groundnut
      containing materials were the most heavily contaminated, the highest value (1862
      ppb) being found in a groundnut cake sample. This mycotoxin was also detected
      occasionally, but to a lesser extent, in some grains and cereals that are of
      nutritional importance in human foods and the livestock industry in Nigeria. The
      toxicological implications of this finding are discussed in relation to human
      health and animal production.

PMID- 8132167
TI  - Seventh International Caffeine Workshop, Santorini, Greece 13-17 June 1993.

PMID- 8132168
TI  - Effects of subchronic exposure to Caramel Colour III on the immune system in
      mice.
AB  - Administration of Caramel Colour III is associated with lymphopenia in laboratory
      animals, especially if the animals are fed a vitamin B6-deficient diet. Recently,
      functional immunological alterations in rats exposed to Caramel Colour III have
      been reported. The component of Caramel Colour III that is responsible for the
      immunological effects has been shown to be 2-acetyl-4-tetrahydroxybutyl imidazole
      (THI). In the present study, female Balb/c mice fed a diet with a relatively high
      vitamin B6 content were exposed to 2 or 10% of a commercial Caramel Colour III
      preparation with a low THI content (less than 25 ppm) in the drinking water for 9
      wk. Although this treatment did not induce a lymphopenia in the exposed mice,
      flow cytometric analysis of lymphocyte subpopulations demonstrated reductions in
      the CD4+ and CD8+ cell populations. In addition, the proliferative response of
      spleen cells to B and T cell mitogens was significantly reduced in the mice
      exposed to 2% Caramel Colour III. No changes were observed in natural killer cell
      activity or in the humoral antibody response to a viral antigen. The results
      indicate that Caramel Colour III that meets the specified limit of less than 25
      mg THI/kg may, nevertheless, interfere with the lymphoid system in mice with an
      adequate vitamin B6 status.

PMID- 8132169
TI  - Antimutagens and anticarcinogens in foods.
AB  - The role of dietary factors in the prevention of major chronic diseases, cancer
      in particular, is under intensive investigation by many laboratories around the
      world. Evidence from epidemiological studies and tests in laboratory animals
      suggests that food consumed by the general population contains certain
      ingredients that may have a role in reduction of the incidence of cancer. It has
      been observed that a number of regular food components, belonging to different
      chemical groups, do possess cancer preventive and/or beneficial outcomes for some
      other diseases; these chemicals, therefore, are frequently collectively known as
      'chemopreventers'. The mode of action of most chemopreventers is still unknown,
      although it appears that many of them are antioxidants, and as such, they may
      scavenge free radicals, formed either during the preparation of food, or by
      biological processes in the body. As free radicals damage lipids, proteins, cell
      membranes and DNA, their removal could prevent development of certain chronic
      diseases, particularly cancer or atherosclerosis. This review summarizes recent
      developments in the search for beneficial effects of regular food ingredients in
      prevention of cancer.

PMID- 8132170
TI  - Contact urticaria and its mechanisms.
AB  - This paper reviews the syndrome of contact urticaria in terms of current
      knowledge regarding pathophysiological mechanisms. The three mechanistic
      categories into which contact urticants are grouped include: (1) immunological
      contact urticaria, (2) non-immunological contact urticaria and (3) uncertain
      mechanism-mediated contact urticaria. Within this schema, the clinical
      manifestations, diagnosis and therapy of contact urticaria are presented.

PMID- 8132171
TI  - Cellular and molecular mechanisms in photochemical sensitization: studies on the
      mechanism of action of psoralens.
AB  - The interaction of chemicals and light to induce sensitization reactions in the
      skin is a complex multistep process resulting in physiological changes in both
      the dermal and epidermal cell layers as well as characteristic inflammatory
      reactions. It is becoming increasingly apparent that an array of growth factors
      and cytokines acting on different components of the skin are involved in the
      regulation of these processes. One of the best characterized classes of chemical
      photosensitizers are the psoralens, a group of compounds that must be activated
      by UV light in wavelengths ranging from 320 to 400 nm (UVA) to initiate their
      biological actions. Recent evidence suggests that the ability of the psoralens to
      induce sensitization reactions, which include alterations in epidermal cell
      growth and differentiation, is highly specific and due to interactions with the
      epidermal growth factor (EGF) receptor. Specific receptor proteins for the
      psoralens have been identified in cytoplasmic and membrane fractions of
      responsive cells. Binding of psoralens to these proteins is of high affinity and
      reversible. UVA light causes psoralens to photoalkylate their receptors, a
      process thought to activate the receptor. One early biochemical event at the cell
      surface membrane linked to psoralen-receptor activation is the inhibition of EGF
      binding and alterations in the structure and function of the EGF receptor. These
      findings suggest that the cell surface membrane is an important target for
      chemical photosensitizers such as the psoralens. In addition, since
      photoactivated psoralens modulate epidermal cell growth and differentiation, the
      ability of these compounds to modify the function of the EGF receptor may
      underlie their biological activity as chemical photosensitizers.

PMID- 8132172
TI  - An approach for development of alternative test methods based on mechanisms of
      skin irritation.
AB  - Recent advances in techniques for culture of human skin cells have led to their
      potential for use as in vitro models for skin irritation testing to augment or
      replace existing rabbit skin patch tests. Our work is directed towards the
      development of cultured human skin cells, together with endpoints that can be
      linked to in vivo mechanisms of skin irritation, as in vitro models for
      prediction of human skin irritation, and for study of mechanisms of contact
      irritant dermatitis. Three types of commercial human skin cell cultures have been
      evaluated, epidermal keratinocytes and partially or fully cornified keratinocyte
      dermal fibroblast co-cultures. Human epidermal keratinocyte cultures (Clonetics)
      were treated with product ingredients and formulations, and the extent of cell
      damage was assessed by incorporation of the vital dye neutral red. Cell damage
      correlated with human skin patch data for ingredient chemicals with the exception
      of acids and alkalis, but did not correlate with skin irritation to surfactant
      containing product formulations. Cultures of human skin equivalents were
      evaluated as potential models for measurement of responses to test materials that
      could not be measured in the keratinocyte/neutral red assay. We developed a
      battery of in vitro endpoints to measure responses to prototype ingredients and
      formulations in human epidermal keratinocyte-dermal fibroblast co-cultures grown
      on a nylon mesh ('Skin2' from Advanced Tissue Sciences) or on a collagen gel
      ('Testskin' from Organogenesis). The endpoints measure cytotoxicity (neutral red
      and MTT vital dye staining, lactate dehydrogenase and N-acetyl glucosaminidase
      release, glucose utilization) and inflammatory mediator (prostaglandin E2)
      release. Initial experiments indicate a promising correlation between responses
      of the Skin2 model to prototype surfactants and in vivo human skin irritation.
      The responses of Testskin cultures to acids and alkalis help to prove the concept
      that a topical application model can measure responses to these materials. These
      results suggest that human skin cell models can provide useful systems for
      preclinical skin irritation assessments, as alternatives to rabbits, for at least
      certain classes of test substances.

PMID- 8132173
TI  - Myeloperoxidase as a biomarker of skin irritation and inflammation.
AB  - Topical exposure to many occupational and environmental chemicals is often
      accompanied by the induction of a cutaneous inflammatory response characterized
      by the influx of polymorphonuclear leucocytes (PMNs). In this study, the
      accumulation of myeloperoxidase (MPO), an enzyme found at high content in PMNs,
      was used as a biomarker to assess the inflammatory response to a number of well
      characterized skin irritants and tumour promoters. Of the chemicals examined,
      there was a good agreement between MPO accumulation and morphometric indicators
      of PMNs. Therefore, it was suggested that MPO accumulation could be an additional
      and useful toxicological tool for determining the dermal irritancy of chemicals.

PMID- 8132174
TI  - beta-Carotene inhibition of chemically induced toxicity in vivo and in vitro.
AB  - In the past several years there has been a great deal of interest in the
      antioxidant beta-carotene and other micronutrients for their protective potential
      against various toxic insults. Two studies concerning the protective effects of
      beta-carotene, which were conducted in our laboratory, are reported here. The
      first involved the role of beta-carotene in modifying two-stage skin
      tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by
      phorbol 12-myristate 13-acetate (PMA, TPA). In this study, the protective effects
      of two types of dietary beta-carotene, a beadlet formulation and crystalline beta
      carotene, were compared in two strains of mice (Skh:HR-1 and CR:ORL Sencar). Mice
      were maintained on food fortified with 3% beta-carotene or on control diets. Mice
      receiving the beta-carotene-supplemented diets had fewer tumours than mice in the
      control groups. However, only in the Skh strain of mice was this difference
      statistically significant. In the second study, an in vitro experiment, BALBc 3T3
      mouse fibroblasts were used to determine beta-carotene's accumulation in cells
      and the ability of these cells to metabolize beta-carotene to vitamin A. This in
      vitro model was also used to show a beta-carotene protective effect towards 8-MOP
      phototoxicity. These studies contributed to the increasing evidence of in vivo
      and in vitro protection by beta-carotene against chemically induced toxicity.

PMID- 8132175
TI  - An assessment of the in vivo clastogenicity of erythrosine.
AB  - In an investigation of the in vivo clastogenic potential of the food colouring
      erythrosine (ER), male B6C3F1 mice were treated by ip injection at doses of 50,
      100 and 200 mg/kg, repeated 24 hr apart. Signs of toxicity were observed at the
      highest dose of ER administered. The three cytogenetic endpoints analysed were
      sister chromatid exchanges (SCEs) in peripheral blood lymphocytes (PBLs),
      micronuclei in bone marrow polychromatic erythrocytes (PCEs), and micronuclei in
      peripheral blood reticulocytes (PBRs). SCE frequencies in PBLs were 4.13, 4.58,
      4.33 and 4.60 SCE/cell at 0, 50, 100 and 200 mg ER/kg, respectively. At the same
      doses, the frequencies of micronucleated PCEs were 3.5, 3.2, 2.0 and 2.5/1000
      PCEs. Micronuclei in PBRs ranged from 1.2 to 3.6 and from 1.4 to 3.0/1000 PBRs in
      control and treated mice, respectively. These results indicate that ER is
      inactive as a clastogen in mouse blood and marrow cells. This result supports the
      hypothesis of a non-genotoxic mechanism for ER carcinogenicity.

PMID- 8132176
TI  - Roles of bladder distension, urinary pH and urinary sodium ion concentration in
      cell proliferation of urinary bladder epithelium in rats ingesting sodium salts.
AB  - The relative importance of bladder distension, urinary pH and sodium ion
      concentration for cell proliferation in the bladder epithelium of rats fed
      various sodium salts was investigated. When a diet containing 5% NaHCO3 was fed
      to male rats, the bladder epithelium showed an increase in replicating cells,
      together with distension, increased urine pH and high urine sodium ion
      concentration. Cell proliferation also occurred when bladders were subjected to
      distension in vivo by mechanical (female) or physiological (male) means.
      Inclusion of CaCO3 in the diet produced high urinary pH without alteration in the
      other factors and did not induce cell proliferation. Increased proliferation
      occurred when CaCO3 was combined with these mechanical or physiological
      treatments. Thus, high urinary pH was of secondary importance to bladder
      distension as a causative factor, but acted to enhance cell proliferation when
      distension occurred. Similar findings were obtained with regard to sodium ion
      concentration. In conclusion, this study demonstrated that bladder distension is
      one of the prerequisites for promoter-induced cell proliferation in the bladder
      epithelium, with high urinary pH and sodium ion concentration.

PMID- 8132177
TI  - Human acute toxicity prediction of the first 50 MEIC chemicals by a battery of
      ecotoxicological tests and physicochemical properties.
AB  - Five acute bioassays consisting of three cyst-based tests (with Artemia salina,
      Streptocephalus proboscideus and Brachionus calyciflorus), the Daphnia magna test
      and the bacterial luminescence inhibition test (Photobacterium phosphoreum) are
      used to determine the acute toxicity of the 50 priority chemicals of the
      Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. These tests and
      five physiocochemical properties (n-octanol-water partition coefficient,
      molecular weight, melting point, boiling point and density) are evaluated either
      singly or in combination to predict human acute toxicity. Acute toxicity in human
      is expressed both as oral lethal doses (HLD) and as lethal concentrations (HLC)
      derived from clinical cases. A comparison has also been made between the
      individual tests and the conventional rodent tests, as well as between rodent
      tests and the batteries resulting from partial least squares (PLS), with regard
      to their predictive power for acute toxicity in humans. Results from univariate
      regression show that the predictive potential of bioassays (both ecotoxicological
      and rodent tests) is generally superior to that of individual physicochemical
      properties for HLD. For HLC prediction, however, no consistent trend could be
      discerned that indicated whether bioassays are better estimators than
      physicochemical parameters. Generally, the batteries resulting from PLS
      regression seem to be more predictive than rodent tests or any of the individual
      tests. Prediction of HLD appears to be dependent on the phylogeny of the test
      species: cructaceans, for example, appear to be more important components in the
      test battery than rotifers and bacteria. For HLC prediction, one anostracan and
      one cladoceran crustacean are considered to be important. When considering both
      ecotoxicological tests and physicochemical properties, the battery based on the
      molecular weight and the cladoceran crustacean predicts HLC substantially better
      than any other combination.

PMID- 8132178
TI  - Missed opportunities in clinical dermatology--the case of 1,2-benzisothiazolin-3
      one.

PMID- 8132179
TI  - The carcinogenic potential of ethylene.

PMID- 8132180
TI  - The role of cancer mechanism in IARC carcinogen classification.

PMID- 8132181
TI  - Committees on Toxicity, Mutagenicity and Carcinogenicity.

PMID- 8132182
TI  - EPA's requirements for dermal irritation and sensitization testing.
AB  - This paper presents an overview of EPA guidelines for dermal irritation and
      sensitization testing (part of Subdivision F Guidelines) for the registration of
      pesticide products [Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)].
      In addition, these data and others may be needed for chemicals submitted for the
      Premanufacture Notification or testing under Section 4 of the Toxic Substances
      Control Act (TSCA). The EPA periodically reviews its recommended test procedures
      and revises them when indicated scientifically.

PMID- 8132183
TI  - Occlusive patch method for skin sensitization in guinea pigs: the Buehler method.
AB  - Currently, the European Community is in the process of discussing the details of
      how to conduct various protocols for safety assessment. Additionally, there is a
      desire that these protocols be harmonized internationally. This presentation
      attempts to describe the critical and non-critical parameters of the protocol for
      detecting potential contact allergens in the guinea pig and also discusses some
      controversial issues. It is also emphasized that the identification of a test
      material as a potential sensitizer is only the first step in the risk-assessment
      exercise.

PMID- 8132184
TI  - A hospital by any other name.

PMID- 8132185
TI  - Managed competition and access to emergency psychiatric care.

PMID- 8132186
TI  - Clozapine treatment of outpatients with schizophrenia: outcome and long-term
      response patterns.
AB  - OBJECTIVE: The purpose of the study was to examine the effects of clozapine in
      treating moderately ill schizophrenic outpatients and to determine the length of
      medication trial needed to identify responders and nonresponders. METHODS: Rates
      of clinical responses, relapses and hospitalizations, and levels of
      symptomatology and functioning were assessed for 30 chronic schizophrenic
      outpatients who received clozapine for one year. For some patients, data on
      relapse and hospitalization during treatment were compared with data from the
      year before treatment. RESULTS: Eighteen of the 30 patients met criteria for
      sustained response; 17 of the responders were identified within the first four
      months of treatment. Patients experienced significantly fewer relapses and
      hospitalizations during treatment than in the previous year. Improvement in
      positive symptoms, general symptomatology, and levels of functioning reached a
      plateau during the first six months of treatment and remained at that level
      during the second six months. Negative symptoms and quality of life showed
      nonsignificant improvements at 12 months. CONCLUSIONS: Results support the use of
      clozapine in treating chronic, residually symptomatic schizophrenic outpatients.
      A four-month clozapine trial may be adequate to detect clinical responders in
      this population.

PMID- 8132187
TI  - Inpatient treatment of patients with severe obsessive-compulsive disorder.
AB  - Patients with obsessive-compulsive disorder may experience severely disabling
      symptoms and require hospitalization. Based on treatment of 77 such patients
      admitted to a long-term general psychiatric research unit over a seven-year
      period, the authors present pharmacologic, psychosocial, and behavioral
      management strategies for treating these patients on general psychiatric units.
      The treatment guidelines require only modest modifications of standard practice
      and can be adapted for use on general units without specialized staff training.
      Some patients with obsessive-compulsive disorder exhibit strong control and
      dependency needs and disrupt the milieu in characteristic ways. These patients
      may generate conflict among staff about whether the patients can control
      obsessive-compulsive behaviors; they may anger other patients because of the
      large amount of staff attention they demand. Educating staff about obsessive
      compulsive patients' control and dependency needs and enlisting the support of
      fellow patients can improve the milieu.

PMID- 8132188
TI  - Training older adults to work as psychiatric case management aides.
AB  - Adults who were age 55 and over were trained to work as case management aides for
      individuals with serious and persistent mental illness. The training program was
      a cooperative effort of several state, academic, and private agencies in the New
      Orleans area, including the department of psychiatry at a state university
      medical center, the State Office of Mental Health, a consortium of colleges and
      universities providing educational opportunities for older adults, and the
      American Association of Retired Persons. The program curriculum included ten
      weeks of classroom instruction and a four-month field practicum. Of the 14
      participants in the initial group of trainees, 13 sought and received employment
      as case aides. At follow-up three months after employment, supervisors of the
      case aides rated their job performance as excellent.

PMID- 8132189
TI  - Health care utilization and costs after entry into an outreach program for
      homeless mentally ill veterans.
AB  - OBJECTIVE: This study evaluated the impact of a Department of Veterans Affairs
      outreach and residential treatment program for homeless mentally ill veterans on
      utilization and cost of health care services provided by the VA. METHODS:
      Veterans at nine program sites (N = 1,748) were assessed with a standard intake
      instrument. Services provided by the outreach program were documented in
      quarterly clinical reports and in residential treatment discharge summaries. Data
      on nonprogram VA health service utilization and health care costs were obtained
      from national VA data bases. Changes in use of services and cost of services from
      the year before initial contact with the program to the year after were analyzed
      by t test. Multivariate analyses were used to examine the relationship of these
      changes to indicators of clinical need and to participation in the outreach
      program. RESULTS: Although utilization of inpatient service did not increase
      after veterans' initial contact with the program, use of domiciliary and
      outpatient services increased substantially. Total annual costs to the VA also
      increased by 35 percent, from $6,414 to $8,699 per veteran per year. Both
      clinical need and participation in the program were associated with increased use
      of health services and increased cost. Veterans with concomitant psychiatric and
      substance abuse problems used fewer health care services than others.
      CONCLUSIONS: Specialized programs to improve the access of homeless mentally ill
      persons to health care services appear to be effective, but costly. Dually
      diagnosed persons seem especially difficult to engage in treatment.

PMID- 8132190
TI  - Indicators of chronic homelessness among veterans.
AB  - OBJECTIVE: This study sought to develop a set of indicators of chronic
      homelessness as a basis for better understanding and treatment of the homeless
      veteran population. METHODS: Chi square analysis and the t test or Mann-Whitney U
      test were used to compare characteristics of veterans who reported long-term
      homelessness (more than 12 months total since age 18) with those of veterans who
      reported short-term homelessness (12 months or less). Subjects were 343 homeless
      male veterans receiving treatment for physical, mental, or substance abuse
      disorders at the West Los Angeles site of the Domiciliary Care for Homeless
      Veterans Program. Variables included history of homelessness, employment history,
      physical and mental health, substance abuse history, social and financial
      support, criminal history, age, ethnic group, education, military service, and
      program discharge status. RESULTS: Veterans experiencing long-term homelessness
      were more likely to be white, to have had a longer period of recent homelessness
      and a greater number of homeless episodes, to have a poor employment history, to
      have symptoms of mental and substance abuse disorders, and to have weaker social
      support. CONCLUSIONS: Results show that variables besides duration of lifetime
      homelessness are important indicators of chronic homelessness.

PMID- 8132191
TI  - Life-styles, adaptive strategies, and sexual behaviors of homeless adolescents.
AB  - OBJECTIVES: The purpose of this study was to gather information about homeless
      adolescents, a largely invisible and understudied population. METHODS: Highly
      trained interviewers conducted structured face-to-face field interviews with 93
      homeless adolescents between the ages of 13 and 17 in the Hollywood area of Los
      Angeles. RESULTS: Seventy-nine percent of the sample had experienced more than
      one homeless episode in their lifetime, and almost a fourth reported more than
      ten episodes. Mean length of time homeless was 440 days (median of 201 days).
      Aggressive and violent behaviors, including stealing, destruction of property,
      and physical fights, were common. The sample had a high prevalence of several
      mental disorders, including conduct disorder with aggression, major depression,
      and alcohol and drug abuse. Almost half had attempted suicide. Nearly all the
      adolescents were sexually active; about a third had more than ten partners in the
      previous year. About a third reported trading sex for money, food, or drugs.
      Although most had basic knowledge of HIV transmission and used some form of birth
      control, little more than half had used a condom in the most recent sexual
      encounter, and 18 percent reported sex with intravenous drug users. CONCLUSIONS:
      Further research on this population is needed, and follow-up contacts in
      particular are essential in developing appropriate and successful service
      programs for them.

PMID- 8132192
TI  - Self-assessed need for mental health services among homeless adults.

PMID- 8132193
TI  - The VA's first comprehensive homeless center: a catalyst for public and private
      partnerships.

PMID- 8132194
TI  - Treatment needs and outcomes of two subtypes of homeless persons who abuse
      substances.

PMID- 8132195
TI  - Prevalence of cognitive impairment among homeless men in a shelter in Australia.

PMID- 8132196
TI  - Psychiatry in post-apartheid South Africa.

PMID- 8132197
TI  - Childhood abuse and neglect.

PMID- 8132198
TI  - A disulfiram support group.

PMID- 8132199
TI  - Improving managed care.

PMID- 8132200
TI  - Lithium-induced polyuria.

PMID- 8132201
TI  - Mental health funds increase slightly in 1994 federal budget.

PMID- 8132202
TI  - Toward a rational design of clinical trials of immunosuppressive agents in
      transplantation.

PMID- 8132203
TI  - The development of Brequinar as an immunosuppressive drug for transplantation.
AB  - The preclinical and clinical characterization of Brequinar sodium has
      demonstrated the potential for the use of this drug as a component of a
      polytherapeutic treatment strategy to prevent the rejection of organ grafts.
      Brequinar, along with several other new immunosuppressive drugs, including
      Mizorbine, 15-deoxyspergualin, and Mycophenolate mofetil, is an antimetabolite
      with immunosuppressive activity and toxic side effects that are distinctly
      different from those of CsA and the newly characterized FK 506. This combination
      of effective antiproliferative activity exhibited by these newer agents and the
      well-established effect of CsA on T-lymphocyte activation offers the potential
      for the development of immunosuppressive regimens that are significantly more
      effective with fewer side effects for the patient. The concept of synergistic
      interaction between these two classes of immunosuppressive agents has been tested
      experimentally and found to be extremely effective for both allograft and
      xenograft models of graft rejection (Cosenza et al. 1993, 1993a, Stepkowski &
      Kahan 1993). It remains to be established that a similar synergism will exist for
      clinical transplantation. The effectiveness of CsA as a primary immunosuppressive
      agent, however, assures the inclusion of CsA in any polytherapeutic approach to
      be tested in the near future. New clinical trials designed to prove efficacy for
      immunosuppressive agents, such as BQR, will use CsA or FK 506 as a primary
      component of the treatment protocol. The combination of immunosuppressive agents
      that will eventually be applied in wide clinical use is not clear. While some new
      immunosuppressive agents have been more extensively tested clinically, BQR
      exhibits a number of unique features that make this compound particularly
      attractive for inclusion in new immunosuppressive regimens. The drug is readily
      soluble in aqueous solutions and can be administered intravenously or orally with
      equal effectiveness. Brequinar exhibits a high level of bioavailability following
      oral administration and an extended half-life that permits less frequent
      administration. While the metabolic byproducts of BQR have not been clearly
      described, there is good evidence that the parent compound exhibits the majority,
      if not all, of the immunosuppressive activity. The ability to monitor the parent
      drug directly or measure the depletion of enzyme products that reflect the
      activity of the drug are important features of the drug that simplify its use in
      a clinical setting. Although BQR exhibits important adverse side effects at high
      doses, the effects of the drug are characteristic of antimetabolites and are
      therefore predictable, constant, and reversible.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8132204
TI  - New immunosuppressive drugs: mechanistic insights and potential therapeutic
      advances.
AB  - Together with CsA, the new macrolide immunosuppressants FK506 and rapamycin have
      proved to be valuable tools in providing new information about key molecular
      events that underlie lymphocyte activation and degranulation. Studies of their
      mechanisms of action have pinpointed the phosphatase calcineurin and protein
      kinases as important signaling mediators in T-cell activation. Other new
      immunosuppressive drugs, including leflunomide, mycophenolate mofetil, brequinar
      sodium and deoxyspergualin exhibit diverse inhibitory effects on cells of the
      immune system and offer considerable promise as adjunctive therapeutic
      immunosuppressants. FK506 appears to be both a valuable therapeutic alternative
      to liver or kidney retransplantation and an alternative primary immunosuppressant
      to CsA in hepatic (especially) and renal transplantation. There is now good
      evidence that immunosuppressive drugs, both old and new, permit the establishment
      of donor-derived, multi-lineage cell chimerism following organ transplantation.

PMID- 8132205
TI  - New immunosuppressants: testing and development in animal models and the clinic:
      with special reference to DSG.

PMID- 8132206
TI  - Homotypic adhesion of rat B cells, but not T cells, in response to cross-linking
      of CD48.
AB  - Rat lymphocytes were found to aggregate in response to monoclonal antibodies to
      the glycosyl phosphatidylinositol (GPI)-anchored surface antigen CD48. This
      clustering required bivalent antibodies but was not Fc mediated. It was blocked
      by inhibitors of cellular metabolism and cytoskeletal function but not by
      antibodies to leucocyte function-associated antigen-1 (LFA-1) or intracellular
      adhesion molecule-1 (ICAM-1). The clusters were found to be due to homotypic
      adhesion of B cells, with T cells showing no response despite expressing equal
      levels of CD48. In addition, thymocytes, which are known to cluster in response
      to cross-linking of Thy-1, another GPI-anchored molecule, were found not to
      respond to cross-linking of CD48. These results suggest that specific signalling
      through CD48 in B cells, but not T cells, and through Thy-1, but not CD48, in
      thymocytes, lead to cell adhesion events. This differential signalling is
      interesting as neither CD48 nor Thy-1 have transmembrane or intracellular
      domains. Levels of CD48-associated protein kinase activity were very low in both
      B and T cells, and no difference in the susceptibility to cleavage with
      phosphatidylinositol-specific phospholipase C was detected between B- and T-cell
      CD48.

PMID- 8132207
TI  - Developmental regulation of bcl-2 expression in the thymus.
AB  - An important factor in shaping the T-cell receptor (TcR) repertoire during
      thymocyte development is the susceptibility of double-positive (CD4+ CD8+)
      thymocytes to induction of apoptosis (negative selection) when the TcR is engaged
      by 'self'-antigens. Recent evidence has suggested that this susceptibility to
      apoptosis may be influenced by the expression of bcl-2, a proto-oncogene known to
      increase the resistance to apoptosis in various cell systems. Using a semi
      quantitative polymerase chain reaction (PCR) technique in conjunction with staged
      embryonic material and purified thymocyte subpopulations we have investigated
      patterns of bcl-2 expression during normal T-cell development. Our results show
      that while bcl-2 alpha gene expression is readily detectable in immature CD3-CD4
      CD8- thymocytes and in mature single-positive TcRhi cells, it is drastically
      reduced in TcR negative double-positive (CD3- CD4+ CD8+) cortical thymocytes of
      intermediate maturity. Careful mapping of bcl-2 alpha re-expression in relation
      to the onset of TcR expression within the population of embryonic thymocytes
      indicates that bcl-2 alpha is up-regulated as soon as TcR molecules are expressed
      on the surface of CD4+ CD8+ thymocytes. Therefore, thymocytes susceptible to
      apoptosis on TcR ligation express bcl-2 alpha mRNA suggesting that changing
      levels of bcl-2 expression are unlikely to be the only determinant regulating
      susceptibility to apoptosis in the thymus. The possible implications of these
      changes in bcl-2 expression regarding other facets of thymocyte development will
      be discussed.

PMID- 8132208
TI  - Isolation, sequence and expression of a cDNA encoding the alpha-chain of the
      feline CD8.
AB  - We have cloned, sequenced and expressed a cDNA encoding the alpha-chain of feline
      CD8. This clone, named FT8-10, has an open reading frame with 720 nucleotides in
      length encoding a protein with 239 amino acid residues. Sequence analysis has
      revealed that the feline CD8 alpha-chain (CD8 alpha) shares significant homology
      with human (T8/Leu-2), bovine (BoCD8), rat (MRC OX8) and mouse (Lyt-2) CD8 alpha
      subunits. Cysteine residues as well as the tyrosine kinase p56lck binding site
      are well conserved. Besides, no putative N-linked glycosylation site was found.
      Interestingly, immunofluorescence analysis of COS-7 cells transfected with feline
      CD8 alpha expression plasmid driven by SR alpha promoter showed that the
      expressed feline CD8 alpha cross-reacted with an anti-human CD8 alpha monoclonal
      antibody OKT8, but did not react with an anti-feline monoclonal antibody, FT-2,
      which is thought to recognize the feline analogue of the human T8/Leu-2 and
      murine Lyt-2 molecules expressed on cytotoxic/suppressor T cells.

PMID- 8132209
TI  - Separation of thymic education from antigen presenting functions of major
      histocompatibility complex class I molecules.
AB  - Participation of transmembrane (TM) and glycosyl-phosphatidylinositol (GPI)
      anchored H-2Db molecules in antigen presentation and thymic selection events was
      investigated using transgenic mice. Both GPI-Db and TM-Db can efficiently present
      H-Y antigen, influenza and lymphocytic choriomeningitis virus (LCMV) peptides to
      primed cytotoxic, H-2Db-restricted T cells. Transgenic mice expressing GPI-Db,
      although unable to reject TM-Db skin grafts, nevertheless generate secondary CTL
      responses which can lyse TM-Db-bearing targets, indicating that GPI-Db mice fail
      to delete all TM-Db-reactive T cells. Furthermore, double-transgenic mice bearing
      GPI-Db and a T-cell receptor (TcR) for H-2Db+LCMV do not positively select
      receptor positive, CD8+CD4- T cells. This paradoxical behaviour of GPI-Db
      molecules suggests that the structural requirements for antigen presentation and
      thymic selection by class I molecules are different and may explain why GPI
      linked class I molecules, such as Qa-2, do not appear to function as restriction
      elements in vivo.

PMID- 8132210
TI  - Glycosylation of IgA is required for optimal activation of the alternative
      complement pathway by immune complexes.
AB  - To investigate the effect of carbohydrate on activation of the alternative
      pathway of complement by IgA immune complexes, aglycosylated monoclonal IgA was
      made biosynthetically in the presence of tunicamycin. When immune complexes were
      incubated with normal human serum (NHS), the aglycosylated IgA immune complexes
      caused less depletion of the alternative pathway activity of the serum. They also
      bound less C3 and produced less terminal complement complexes. The binding of C3
      to both immune complexes was mainly through hydroxylamine sensitive ester bonds.
      C3 did not bind to free IgA.

PMID- 8132211
TI  - Paradoxical reconstitution of complement activity following plasma transfusion of
      an individual with deficiency of the seventh component of complement.
AB  - A subject deficient in the seventh component of complement (C7) was
      plasmapheresed with 660 ml C7-sufficient plasma. The expected reconstitution of
      C7 activity, followed by exponential decay, was not observed. During day 1, serum
      haemolytic C7 and total haemolytic complement were undetectable and C7 levels
      were very low by C7 ELISA. However, low levels of circulating fluid phase
      terminal complement complex (TCC) were detected. On day 2 about microgram C7/ml
      serum was detected and this rose to 6 micrograms/ml by day 17. Functional
      complement activity was also present. At day 28 the serum C7 and total haemolytic
      complement had dropped to pretransfusion levels. A low level of C5b6 was present
      in pretransfusion serum and this increased markedly immediately following
      transfusion when the patient's serum also acquired C7 consuming activity.
      Throughout the study low levels of anti-C7 antibodies were present but there was
      no evidence that antibody was directly responsible for the C7 consumption.
      Nevertheless antibody-antigen interactions could have generated circulating C5b6.
      C5b6 has been shown previously to have the capacity to inhibit C7 activity in
      vitro. Investigations of the C7 circulating on days 2-17 demonstrated normal
      molecular weight, functionally active C7. The donor sera and the recirculating C7
      allotyped C7-1 by isoelectric focusing; however, the recirculating C7 showed
      additional weak bands with C7 functional activity, suggesting a possible genetic
      or acquired abnormality. Although the disappearance of C7 immediately post
      transfusion may be explained by the presence of C5b6, there is no satisfactory
      explanation for the rising C7 levels on days 2-17 and we cannot exclude temporary
      C7 secretion by the patient.

PMID- 8132212
TI  - A longitudinal study of per cent agalactosyl IgG in tuberculosis patients
      receiving chemotherapy, with or without immunotherapy.
AB  - An increased percentage of circulating IgG molecules that lack galactose from the
      oligosaccharides on the CH2 domain correlates with disease severity in
      tuberculosis, rheumatoid arthritis and Crohn's disease. We have recently observed
      that a single injection of 10(9) autoclaved Mycobacterium vaccae given to
      tuberculosis patients 7 days after the initiation of chemotherapy causes
      accelerated clinical improvement, and clearance of bacilli from the sputum. We
      now show that this immunotherapy also causes rapid loss of agalactosyl IgG,
      detectable within 14-21 days, whereas chemotherapy alone causes agalactosyl IgG
      to rise further for up to 2 months. There is simultaneous inhibition of the
      antibody response to lipoarabinomannan, and transient enhancement of the
      tuberculin skin-test response. These findings are compatible with a shift from
      antibody production towards increased cell-mediated immunity. The ideal treatment
      for tuberculosis would supplement a truncated course of chemotherapy with an
      immunotherapeutic preparation able to down-regulate the Koch phenomenon and
      replace it with an efficiently bactericidal mechanism. We tentatively postulate
      that a fall in per cent agalactosyl IgG [%Gal(0)] in tuberculosis patients may be
      a marker of such a change.

PMID- 8132213
TI  - Isolation and characterization of three subpopulations of IgG in the common cat
      (Felis catus).
AB  - Although the cat is an important model for a number of human diseases little is
      known of its basic humoral immunity. In this study we have isolated three
      subpopulations of IgG from cat serum by DEAE anion-exchange chromatography and
      protein A affinity chromatography. Subpopulation 3 did not bind to DEAE
      equilibrated in 2 mM phosphate buffer pH 8.0 while subpopulations 1 and 2 were
      eluted, as a mixed population, with a salt gradient between 3 mM and 25 mM. When
      this fraction was loaded onto protein A-Sepharose two distinct peaks were always
      generated in a pH gradient (pH 8.0-2.1). The first of these, subpopulation 2, was
      eluted on average at pH 4.3 while the second, subpopulation 1, was eluted on
      average at pH 3.4. Subpopulations 1 and 2 had similar immunoelectrophoretic
      mobilities and isoelectric points while subpopulation 3 was more cathodic in both
      tests. Antisera produced in both mice and rabbits were rendered specific, by
      absorption of cross-reacting antibodies, for determinants on the heavy chain of
      each subpopulation as shown by Western blotting. The data suggest, but are not
      conclusive, that each of these subpopulations are distinct subclasses of IgG.

PMID- 8132214
TI  - Macrophage response to bacteria and bacterial products: modulation of Fc gamma
      receptors and secretory and cellular activities.
AB  - The ability of bacteria and bacterial products to modulate the expression of Fc
      gamma receptors and major histocompatibility complex (MHC) class II molecules in
      resting rat bone marrow-derived mononuclear phagocytes (BMM phi) was determined
      by means of flow cytometry (FCM). Binding of IgG via Fc gamma receptors was
      considerably enhanced by most microbial agents; bacterial lipopolysaccharide,
      lipoteichoic acid and some intact bacteria proved to be as active as interferon
      gamma (IFN-gamma) and augmented binding of IgG via high- and low-affinity Fc
      gamma receptors. In contrast, expression of MHC class II molecules by BMM phi was
      only slightly affected by the microbial agents. Additional findings attest that
      resting unprimed rat BMM phi are able to respond directly to Gram-negative and
      Gram-positive bacteria and to some of their products with the expression of
      marked secretory [in particular tumour necrosis factor-alpha (TNF-alpha) and
      nitrite] and cellular activities (TNF-alpha-independent tumoricidal activity).
      This extensive, direct type of macrophage activation may substantially amplify
      the capability of these cells to cope with these infectious agents in first-line,
      non-specific host defence.

PMID- 8132215
TI  - Dexamethasone induces apoptosis in mouse natural killer cells and cytotoxic T
      lymphocytes.
AB  - Glucocorticoid hormones (GCH) induce apoptotic cell death in immature thymocytes
      through an active mechanism, characterized by extensive DNA fragmentation into
      oligonucleosomal subunits. This requires macromolecular synthesis and is
      inhibited by protein kinase C (PKC) inhibitors, interleukin-4 (IL-4) and heat
      shock (hs). We performed experiments to analyse the possible effect of GCH on
      more differentiated lymphocytes, i.e. mouse natural killer (NK) cells and CD8+
      alloreactive cytotoxic T lymphocytes (CTL). The results show that dexamethasone
      (DEX) induces DNA fragmentation and cell death in NK cells and CTL in vitro. In
      both NK cells and CTL, DEX-induced apoptosis is inhibited by IL-2 and IL-4 but,
      unlike that induced in thymocytes, is augmented by mRNA and protein synthesis
      inhibitors, PKC inhibitors and HS.

PMID- 8132216
TI  - Adoptive transfer of unresponsiveness to allogeneic skin grafts with hepatic
      gamma delta + T cells.
AB  - C3H/HEJ mice injected with irradiated multiple minor incompatible B10.BR lymphoid
      cells via the portal vein showed delayed rejection of subsequent B10.BR skin
      grafts. Similar delayed rejection was produced by lateral tail vein injection of
      B10.BR hepatic mononuclear cells or H-2k cells pulsed in vivo with B10 minor
      histocompatibility antigens. Inhibition of C3H anti-B10.BR immunity in vivo
      (assessed by delayed graft rejection) and in vitro (assessed by B10.BR-induced
      lymphokine production) can be transferred by radioresistant, plastic-adherent
      F4/80+33D1-CD4-CD8-alpha beta TcR-gamma delta TcR- mononuclear hepatic cells from
      (C3H/HEJ x C3H.SW)F1 mice injected 36 hr earlier with 100 x 10(6) irradiated
      spleen cells. By 10 days post-injection, cells transferring delayed rejection are
      radiosensitive, plastic non-adherent, F4/80-33D1-CD4-CD8- alpha beta Tc+- gamma
      delta TcR+ cells. Injection of interleukin-2 (IL-2) in vivo into mice receiving
      pretreatment with B10.BR cells via the portal vein, or adoptive transfer into
      such mice of immune anti-B10.BR lymphoid cells, abolished delayed rejection on
      subsequent skin grafting. Delayed rejection or modulation of lymphokine
      production was associated in all cases with suppression of IL-2 production and
      preferential retention of IL-4 production from cells stimulated in vitro.

PMID- 8132217
TI  - Expression on porcine gamma delta lymphocytes of a phylogenetically conserved
      surface antigen previously restricted in expression to ruminant gamma delta T
      lymphocytes.
AB  - A 180,000 MW molecule has been identified on porcine leucocytes that is the
      homologue of the 215,000/300,000 MW WC1 (T19) leucocyte antigen previously
      considered to be restricted to ruminants. In ruminants the WC1 molecule is
      expressed by a T-cell subpopulation that is CD2-CD4-CD8-CD5+ and that is gamma
      delta T-cell receptor positive (TcR+). In pigs, the 180,000 MW molecule,
      identified by a new monoclonal antibody CC101, is expressed by a gamma delta TcR+
      T-cell subpopulation that is also CD2-CD4-CD8-. The p180+ cells are a major T
      cell subpopulation comprising approximately 40% of the peripheral blood
      mononuclear cells from 6-9-month-old pigs. Expression of p180 identifies the
      majority of the CD2-CD4-CD8- T cells in porcine blood. The p180+ T cells have a
      distribution in lymphoid tissues that is distinct from that of T cells that
      express the CD2, CD4 or CD8 molecules. They are evident particularly in the
      thymic medulla, the epithelium, lamina propria and interfollicular areas of the
      small intestine, and the superficial dermis of the skin, but largely absent from
      conventional T-dependent areas of secondary lymphoid tissue.

PMID- 8132219
TI  - Nedocromil sodium acts directly on human B cells to inhibit immunoglobulin
      production without affecting cell growth.
AB  - The effect of nedocromil sodium (NES) on human immunoglobulin (Ig) isotypes, IgG
      subclasses and IgA subclasses was studied. NES inhibited IgM and IgA1 production
      from human lymphoblastoid B-cell lines CBL and GM-1056, respectively, in a dose
      dependent fashion. This inhibition was not due to decreased cell growth as cell
      proliferation was not affected by NES and cell viability was always greater than
      98%. Of the various cytokines tested, interleukin-4 (IL-4) reduced the NES
      induced inhibition of Ig production, whereas other cytokines, including IL-1
      beta, IL-2, IL-3, IL-5, IL-6, interferon-alpha (IFN-alpha), IFN-gamma,
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin
      (Epo) failed to do so. The reducing effect of IL-4 was blocked by anti-IL-4
      antibody but not by control IgG. Moreover, IFN-alpha and IFN-gamma, but not GM
      CSF, overcame the reducing effect of IL-4. NES also inhibited production of IgM,
      IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2 by tonsillar B cells stimulated with
      Staphylococcus aureus Cowan strain I (SAC) and IL-6 without affecting
      proliferation. This inhibition was reduced by IL-4 specifically. These results
      indicate that in addition to its anti-allergic function, NES may act as a B-cell
      regulatory reagent.

PMID- 8132218
TI  - Follicular dendritic cell function and murine AIDS.
AB  - Infection of mice with LP-BM5 elicits an immunodeficiency state referred to as
      murine acquired immune deficiency syndrome (MAIDS). Shortly after infection,
      retrovirus particles become associated with follicular dendritic cells (FDC) and
      this study was undertaken to determine whether retroviruses alter FDC functions.
      The FDC functions examined included the ability to: (1) retain antigen (Ag)
      trapped prior to infection; (2) trap new Ag after infection; (3) maintain
      specific IgG responses; and (4) provide co-stimulatory signals to B cells. Mice
      were infected with LP-BM5 and the ability of their FDC to trap and retain 125I-Ag
      (HSA) was assessed. Serum anti-HSA levels were monitored and FDC co-stimulatory
      activity was indicated by increased B-cell proliferation. HSA trapped on FDC
      prior to infection began to disappear by 3 weeks and was practically gone by 6
      weeks. Serum anti-HSA titres were maintained normally for about 3 weeks after
      infection and then declined precipitously. The ability of FDC to trap new Ag
      began to disappear around the second and third week of infection and was markedly
      depressed by the fourth week. However, FDC recovered from infected mice retained
      their ability to co-stimulate anti-mu- and interleukin-4 (IL-4)-activated B cells
      throughout a 5-week period. In short, the ability of FDC to trap and retain
      specific Ag and maintain specific antibody levels was markedly depressed after
      retrovirus infection. However, FDC from infected mice continued to provide co
      stimulatory signals and these signals may contribute to the lymphadenopathy and
      splenomegaly characteristic of MAIDS.

PMID- 8132220
TI  - In vitro modulation of interleukin-1 beta secretion by cultured rat doxorubicin
      stimulated whole glomeruli and dissociated mesangial glomerular cells.
AB  - Doxorubicin-stimulated whole rat glomeruli and dissociated mesangial and resident
      glomerular macrophage cells produced the release of interleukin (IL)-1 beta
      cytokine. This activity increased after the addition of lipopolysaccharide (LPS)
      or LPS plus indomethacin to the cultures. In the presence of WEB2086 [platelet
      activating factor (PAF)-acether antagonist], this activity showed a drastic
      reduction, without modification after sodium furegrelate (thromboxane synthetase
      inhibitor) was added to the cultures. Our results also demonstrate that this IL-1
      beta activity is mainly produced by glomerular-resident macrophage cells. These
      findings support the important role by both IL-1 beta and PAF-acether mediator
      factors, at the cellular level, in the rat model of doxorubicin-induced
      nephrosis.

PMID- 8132221
TI  - Differences in IL-4 release by PBMC are related with heterogeneity of atopy.
AB  - Atopy is heterogeneous and the IgE immune response of patients allergic to a
      single allergen (monosensitized) differs from that of those allergic to multiple
      allergens (polysensitized). Since interleukin-4 (IL-4) and interferon-gamma (IFN
      gamma) regulate human IgE synthesis in vitro, we determined whether cytokines may
      be involved in the heterogeneity of atopy by comparing the serum IgE and sCD23
      titres to the cytokine profile of T lymphocytes from 44 atopic patients (13 mono-
      and 31 polysensitized) and seven non-atopic subjects. Monosensitized patients
      were allergic to grass or cypress pollens or house dust mites, and polysensitized
      ones to many pollen species (n = 5) or many allergens (n = 26). Total serum IgE
      was lower in the control group than in both atopic groups and in the
      monosensitized group than in the polysensitized one. IgE immunoblots to orchard
      grass pollen and house dust mites were less heterogeneous in the monosensitized
      group than in the polysensitized one. IL-4 production by in vitro-activated
      peripheral blood mononuclear cells (PBMC) was significantly higher in the
      polysensitized group than in the monosensitized, and marginal in the control
      group. In contrast, IFN-gamma production was strongly reduced in both atopic
      groups, and IL-2 production comparable in the three groups. IgE and soluble CD23
      (sCD23) release was higher in the atopic groups than in the control, and higher
      in the polysensitized group than in the monosensitized one. This study shows that
      PBMC of mono- and polysensitized subjects have a different IL-4 and sCD23 profile
      and suggests that human beings may be classified into high and low IgE responders
      on the basis of IL-4 production.

PMID- 8132222
TI  - Synergistic effect of IL-4 and TNF-alpha in the induction of monocytic
      differentiation of a mouse myeloid leukaemic cell line (WEHI-3B JCS).
AB  - We have previously shown that non-cytotoxic concentrations (600-1200 U/ml) of
      recombinant mouse tumour necrosis factor-alpha (TNF-alpha) can induce
      differentiation of a subclone (JCS) of the WEHI-3B myelomonocytic leukaemia cell
      line into mature cells with the characteristics of macrophages. In the present
      study, the effects of recombinant mouse interleukin-4 (IL-4), either alone or in
      combination with mouse TNF-alpha, on the growth and differentiation of JCS cells
      were examined. IL-4 alone (20-5000 U/ml) inhibited the growth of JCS cells in a
      dose-dependent manner but did not induce cell differentiation. However,
      combinations of IL-4 and TNF-alpha acted in synergy to inhibit cell proliferation
      and induce monocytic differentiation of JCS cells, as shown by increased
      expression of the macrophage differentiation antigens (F4/80, Mac-1), stimulation
      of phagocytic activity, induction of non-specific esterase and NBT-reducing
      activities, increased plastic adherence and morphological criteria. Similar
      synergistic interactions were also shown by human TNF-alpha and mouse IL-4,
      indicating that TNF-alpha might exert its effects through the low-affinity (p55)
      TNF receptors. Moreover, the clonogenicity of JCS cells in vitro and their
      tumorigenicity in vivo were significantly reduced by combined TNF-alpha and IL-4
      treatment. Our results indicate that TNF-alpha can act as a differential signal
      for JCS cells and that its effects are modulated by IL-4. Therefore, the
      combination of TNF-alpha and IL-4 may be useful in the treatment of some forms of
      myelomonocytic leukaemia.

PMID- 8132223
TI  - TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell
      line KU812.
AB  - The basophilic leukaemia cell line KU812 can be induced to differentiate into
      basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line.
      KU812 cells express affinity receptors for IgE, produce histamine and tryptase
      and have the capacity for IgE-mediated histamine release. In this study we have
      examined the cytokines, produced by the Mo cell line, which are responsible for
      the observed differentiation-inducing effect in the KU812 cell line. It was shown
      that interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced
      differentiation in the KU812 cells and that these cytokines were responsible for
      the differentiation-inducing effect of the Mo supernatant. Other cytokines
      tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte-macrophage colony
      stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on
      the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and
      IL-6 after 3 days cultivation with conditioned media from the Mo T-cell line.
      Untreated cells showed no detectable levels of TNF-alpha or IL-6 receptors
      indicating induction of these receptors during differentiation. Spontaneous
      differentiation was shown to occur under serum-free conditions which may be the
      result of endogenous IL-6 production through an autocrine loop. The activity of
      TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to
      the respective cytokine.

PMID- 8132224
TI  - Role of tumour necrosis factor-alpha in ultraviolet B light-induced dendritic
      cell migration and suppression of contact hypersensitivity.
AB  - Irradiation with ultraviolet B light (UVB) is known to suppress contact and
      delayed hypersensitivity response to a variety of antigens encountered within a
      short period following exposure. Such irradiation results in loss of Langerhans'
      cells and in synthesis of tumour necrosis factor-alpha (TNF-alpha) in the
      epidermis. In the present study the effect of broad-band (270-350 nm) and narrow
      band (311-312 nm) UVB on the induction of contact hypersensitivity (CH) and on
      dendritic cell (DC) numbers in draining lymph nodes (DLN) of mice was examined.
      Broad-band UVB induced the accumulation of DC in DLN and this increase was
      substantially abrogated by treatment of mice with neutralizing antibody to TNF
      alpha before irradiation. In addition, irradiation before sensitization with
      oxazolone resulted in a suppressed CH response. The suppression was negated to a
      considerable extent by TNF-alpha antibodies, administered before irradiation.
      Thus, one of the major effects of broad-band UVB is likely to be the synthesis of
      epidermal TNF-alpha which, in turn induces the migration of Langerhans' cells to
      DLN and leads to an impairment of their activity or function. Conversely narrow
      band UVB did not result in an accumulation of DC in DLN or in a suppressed CH
      response. Such irradiation does, however, cause the isomerization from trans to
      cis-UCA in the epidermis. Cis-UCA has been proposed as a photoreceptor for UV and
      suppresses immune responses in a variety of experimental systems. Thus cis-UCA
      does not act through TNF-alpha induction or by influencing DC migration, and
      other studies indicate that histamine-like receptors in the skin may be involved.

PMID- 8132225
TI  - Colonic epithelial cell lines as a source of interleukin-8: stimulation by
      inflammatory cytokines and bacterial lipopolysaccharide.
AB  - Cytokines produced by intestinal epithelial cells may function as signals to
      neighbouring immune and inflammatory cells. We investigated production of the
      neutrophil and T-lymphocyte chemotactic cytokine interleukin-8 (IL-8) by
      intestinal epithelial cells using four colonic adenocarcinoma cell lines, T84,
      CaCo-2, HT29 and SW620, as a model system. These cell lines secreted substantial
      amounts of IL-8 if stimulated with IL-1 beta, tumour necrosis factor-alpha (TNF
      alpha) or interferon-gamma (IFN-gamma), except CaCo-2 cells, which responded only
      to IL-1 beta. Bacterial lipopolysaccharide (LPS) was also an efficient stimulus
      of IL-8 release in SW620 and HT29 cells, whereas T84 and CaCo-2 cells were
      completely unresponsive to LPS, IL-8 secretion was greater at 4 hr after
      stimulation and was accompanied by induction of IL-8 messenger RNA. In T84 cells
      IFN-gamma and epidermal growth factor (EGF) stimulated IL-8 secretion
      synergistically with TNF-alpha, whereas in SW620 cells this synergism occurred
      only between IFN-gamma and TNF-alpha. IL-4, IL-10 and transforming growth factor
      beta (TGF-beta), which can down-regulate IL-8 production in macrophages, had no
      effect on IL-8 generation by our cell lines. Adenocarcinoma cell culture
      supernatants also induced rapid transients of intracellular calcium in
      neutrophils. Depending on cell line and stimulus, supernatant bioactivity was
      completely or partially abrogated by neutralizing antibodies to IL-8, indicating
      that the cell lines investigated also generate other neutrophil-activating
      factors. IL-8 and possibly other chemokines generated by colonic adenocarcinomas
      may help to attract tumour-infiltrating leucocytes. Possibly, normal intestinal
      epithelial cells also have the potential to secrete this potent chemoattractant
      and thus might contribute to inflammatory responses of the intestinal mucosa, for
      example in inflammatory bowel disease.

PMID- 8132226
TI  - Enhancement of human monocyte beta-glucan receptors by glucocorticoids.
AB  - Glucocorticoids are potent and diverse in their effects on mononuclear
      phagocytes, ranging from suppression to stimulation. To determine whether
      glucocorticoids affected functions mediated by monocyte beta-glucan receptors,
      human mononuclear cells (MNC) were incubated for 20 hr at 37 degrees with 20-2000
      nM dexamethasone or hydrocortisone, and the monocytes were subsequently assayed
      for their ingestion of purified yeast glucan particles. Prior treatment with
      dexamethasone or hydrocortisone enhanced monocyte phagocytosis of glucan
      particles in a dose-dependent manner and both steroids effected a twofold
      increase at 200 nM. Monocytes from three different donors were assessed for
      secretion of beta-N-acetylglucosaminidase, and all were increased by exposure to
      200 nM dexamethasone for 20 hr and subsequent stimulation with glucan particles
      for 2 hr; the average percentage net release was 16.2%. The enhancement in
      monocyte phagocytosis of glucan particles did not result by culture of MNC with
      beta-oestradiol, progesterone, testosterone or spironolactone, indicating a
      specificity for corticosteroids with glucocorticoid activity. The increases in
      phagocytic activity by monocytes that had been exposed during culture to either
      200 nM dexamethasone or 200 nM hydrocortisone were both reduced by 40-50% by
      pretreatment of monocytes with the anti-idiotype (anti-Id) that recognizes beta
      glucan receptors. Exposure of cells to 200 nM dexamethasone for 2 hr and washing
      before continued incubation for 18 hr in steroid-free media resulted in
      stimulation of monocyte beta-glucan receptors, whereas similar exposure without
      subsequent culture or with the addition of cycloheximide for the final 18 hr did
      not. Thus, glucocorticoids enhance monocyte functions mediated by beta-glucan
      receptors, and this stimulation is dependent on proteins that are newly
      synthesized during culture.

PMID- 8132227
TI  - Nasal mucociliary clearance & mucus pH in patients with diabetes mellitus.
AB  - Nasal mucociliary clearance (NMC) time and nasal mucus pH were studied in 50
      patients suffering from diabetes mellitus and in a group of 50 healthy non
      smokers and non-alcoholic controls. NMC time and pH values were found to be
      significantly increased in diabetics (NMC = 18.02 +/- 5.08 and pH = 7.96 +/-
      0.75) as compared to controls (NMC = 7.49 +/- 1.06 and pH 6.43 +/- 0.67). The
      increase in NMC and pH was much more in patients having insulin dependent
      diabetes mellitus (IDDM) (NMC - 20.87 +/- 4.71 and pH -8.38 +/- 0.56) than in non
      insulin dependent diabetes mellitus (NIDDM) (NMC - 15.16 +/- 3.67 and pH -7.53 +/
      0.687) and also when the duration of disease was more than 10 yr (NMC - 22.36 +/
      4.36 and pH -8.47 +/- 0.607). This impairment was attributed to osmotic diuresis
      with loss of water and electrolytes from all parts of the body and also small
      vessel abnormalities encountered in diabetes.

PMID- 8132228
TI  - Serum beta-N-acetylhexosaminidase, carcinoembryonic antigen & sialic acid in
      benign & malignant extrahepatic biliary obstruction.
AB  - Study of tumour markers to differentiate benign and malignant extra hepatic
      biliary obstructions showed that levels fo serum beta-N-acetylhexosaminidase and
      lipid associated sialic acid were not different in the two groups. The levels of
      carcinoembryonic antigen (CEA) and total sialic acid (TSA), on the other hand,
      were significantly higher in patients with the malignant biliary obstruction. At
      a cut-off value of 6.4 ng/ml (mean + 2SD) CEA had 66.7 per cent true positivity
      in malignancy 100 per cent true negativity in control and 78 per cent true
      negativity in the benign group. Similarly, TSA at a cut off value of 60 mg/dl had
      61 per cent true positivity in malignancy, 90 per cent true negativity in
      controls and 70 per cent true negativity in the benign group. These two tumour
      markers appear to have similar diagnostic potential for malignant extrahepatic
      biliary obstruction. Surgical management of the malignant obstruction did not
      result in a decline in the elevated levels of these two markers during the post
      surgical period of 7 days.

PMID- 8132229
TI  - Humoral immunological profile of workers exposed to asbestos in asbestos mines.
AB  - Humoral immunological profile including immunoglobulins IgG, IgA, IgM, C-reactive
      protein, rheumatoid factor, antinuclear antibodies and circulating immune
      complexes were studied in a representative sample of 36 workers suffering from
      asbestosis (group A), 35 workers who are exposed to asbestos but not having
      evidence of asbestosis (group B) and 28 control workers (group C). Mean IgG and
      IgA levels were found to be significantly higher in the two exposed groups than
      in the controls. Circulating immune complexes of IgG, IgA and IgM class were
      detected in a significant percentage of cases in exposed groups than in controls.
      In groups A and B, the percentage of positive ANF cases was much higher than in
      the controls. The results suggest that immunological changes are associated with
      exposure to asbestos and these may play an important role in the pathogenesis of
      the disease process.

PMID- 8132230
TI  - Chest malignancies & serum immunoglobulin E.
AB  - Serum IgE levels were measured by the radioimmunoassay technique in the sera of
      53 patients with neoplastic chest diseases. Forty seven patients had malignant
      chest tumours and another 6 had benign tumours or mediastinal cysts. They
      included 33 smokers and 20 non-smokers. For comparison, 30 normal non-smoking
      controls matched for age and sex were included. The serum IgE levels in patients
      with chest malignancies showed an increase as compared to controls. The IgE
      levels increased significantly in adenocarcinoma (P < 0.01) and squamous cell
      carcinoma (P < 0.001), while they were not raised in poorly differentiated
      carcinoma. There was no significant difference between the serum IgE levels of 32
      smokers and 15 non-smokers with malignant chest tumours.

PMID- 8132231
TI  - Zinc, copper & iron contents in cooked foods & estimates of their daily intakes
      in young hostel residents.
AB  - Dietary zinc, copper and iron intakes of 19 men and 11 women (aged 18-25 yr) were
      determined during three periods of five consecutive days each, using, weighment
      method and atomic absorption analysis of food samples. Daily zinc, copper and
      iron intakes of men ranged from 13.1 +/- 1.2 to 15.3 +/- 1.4 mg/d, 1.62 +/- 0.15
      to 1.84 +/- 0.17 mg/d and 20.5 +/- 2.8 to 29.1 +/- 4.5 mg/d and of women 8.8 +/-
      2.0 to 9.0 +/- 1.6, 1.42 +/- 0.23 to 1.69 +/- 0.62, and 10.0 +/- 2.4 to 14.7 +/-
      2.6 mg/d respectively. Cereals provided 67.7 per cent of dietary zinc, 47.7 per
      cent copper and 62 per cent iron in men and 60 per cent of Zn, 44 per cent of Cu
      and 59 per cent of Fe in women, suggesting lower contribution of cereals to Cu
      intakes than Zn and Fe. Men had mineral intakes close to the recommended
      allowances for Indians, whereas the intakes of women were 30 to 60 per cent
      lower. When expressed as mg/1000 kcal, lower calorie intakes of women were
      responsible for their low mineral intakes. Intra-individual variation in mineral
      intakes was higher (18.39%) than that of energy intakes (14-17%) in both men and
      women. Phytate: Zn molar ratios were > 15 indicating risk of zinc deficiency in
      these students.

PMID- 8132232
TI  - Acute haemolytic episodes & fava bean consumption in G6PD deficient Iraqis.
AB  - The relation between fava bean ingestion and the occurrence of a haemolytic
      episode was studied in 102 glucose-6-phosphate dehydrogenate (G6PD) deficient
      Iraqi patients. None of the patients (mean age 12.8 yr) had a documented similar
      illness earlier, although all of them gave history of reported regular fava bean
      ingestion in the past. Further, none of the three patients who were rechallenged
      (2-3 months later) by the beans developed any clinical or laboratory evidence of
      haemolysis. The incidence of the haemolytic episodes was found to peak in April,
      while the fava bean season extends from February to June. This study thus does
      not support a causal relation between the bean ingestion and the haemolytic
      episodes in G6PD deficient Iraqis. Possibly, some other factor such as a viral
      infection may be involved.

PMID- 8132233
TI  - Acinar cells free pure islets for transplantation from Indian bonnet monkeys.
AB  - Pancreatic islets, completely free of acinar cells were isolated from the Indian
      bonnet monkey Macaca radiata radiata for transplantation studies. The monkey
      pancreas was inflated with Hank's solution containing collagenase (5 mg/ml).
      After incubation for 25 min at 37 degrees C the friable pancreas was teased
      apart. The fragments were aspirated with a 20 ml disposable syringe (without
      needle) twice and ejected. After the third aspiration, the homogenate was poured
      over nylon mesh. Islets were separated from the filtrate by centrifugation in
      Ficoll gradients and then hand picked. Histological examination revealed that the
      islets were completely free of acinar cells. On exposure to glucose, the islets
      responded normally with increased insulin release. They retained their structural
      integrity after transplantation under the renal capsule of normal rats treated
      with cyclosporine. The deleterious effect of exocrine cells after transplantation
      will be completely eliminated by this islet preparation.

PMID- 8132234
TI  - Characterisation of the routes of methionine transport in mouse mammary glands.
AB  - The sites of methionine uptake by mammary glands from late pregnant and lactating
      mice were studied in vitro. Using the specific A system inhibitor, N
      (methylamino) isobutyric acid (MeAIB) and the specific L system inhibitor, 2
      amino-bicyclo (2.2.1) heptane 2-carboxylic acid (BCH), we have defined four modes
      of methionine entry into these tissues. (i) A sodium-dependent A system with a
      Vmax of 13.4 and 18.8 n mol/g cells/min in pregnant and lactating mice,
      respectively. This mode of entry was completely inhibited by MeAIB and its Km
      value was similar (0.45 mM) in both groups. (ii) A sodium-dependent mode with a
      Vmax of 6.7 and 12.4 n mol/g cells/min and a Km of 0.24 and 0.46 mM in pregnant
      and lactating mice, respectively. This mode of entry was insensitive to
      inhibition by MeAIB, and was similar to the ASC (alanine, serine, cysteine)
      system in other tissues. (iii) A sodium-independent L system with a Vmax of 13.8
      and 30.0 n mol/g cells/min and a Km of 0.27 and 0.46 mM in pregnant and lactating
      mice, respectively. This mode of entry was completely inhibited by BCH. (iv) A
      sodium-independent non-specific entry amounting to 25 per cent of the total entry
      at 0.1 mM external methionine which was not inhibited by high concentration of
      BCH. The results of our studies show an increase in the number of active carriers
      of the A, ASC and L systems of methionine uptake in mammary glands of mouse
      during lactation.

PMID- 8132235
TI  - Lipid peroxide metabolism in oophorectomised rats.
AB  - The effect of bilateral oophorectomy and the administration of beta-estradiol on
      lipid peroxide metabolism were studied in rats. The lipid peroxide levels were
      measured in the oophorectomised and the estradiol administered animals. The level
      of lipid peroxide increased in the liver in oophorectomised animals, whereas no
      change was observed in the heart. The activity of antiperoxidative enzymes
      superoxide dismutase and catalase was found to be decreased in both the liver and
      the heart. Oophorectomy resulted in the elevation of serum ceruloplasmin.
      Administration of estradiol to oophorectomised rats restored the altered lipid
      peroxide levels.

PMID- 8132236
TI  - Isolation & cryo-preservation of human foetal articular chondrocytes.
AB  - An attempt to determine the ideal temperature and duration of storage of human
      foetal chondrocytes yielded highly cellular preparations with no alteration in
      morphology or loss of viability. Initial digestion with activated papain was
      followed by incubation in 0.5 per cent collagenase. Trypan blue exclusion test
      revealed a viability count of 95-99 per cent and radioactive thymidine uptake a
      corresponding labelling index. On TEM no subcellular damage was evident. The
      isolated viable chondrocytes were further banked at varying temperatures of +4
      degrees, -4 degrees, -30 degrees, -79 degrees and -196 degrees C, in Eagles MEM
      with 10 per cent dimethyl sulfoxide. Post storage morphology and viability of
      these cells, thawed after durations of 20 h, 1 wk, 1, 2, 3, 4 and 6 months, were
      compared with prestorage readings in an attempt to define the ideal temperature
      for banking. Storage in liquid nitrogen at -196 degrees C demonstrated excellent
      preservation even at the end of six months with minimal subcellular change.
      Electron microscopy and labelling index were found to be superior to Trypan blue
      exclusion test in assessing the stored chondrocytes for retention of their
      functions.

PMID- 8132237
TI  - Nitrogen monoxide in health and disease.

PMID- 8132238
TI  - Luteal phase contraception with mifepristone (RU 486) in the rhesus monkey.
AB  - Mifepristone (RU 486), an antiprogesterone, is a promising luteal phase
      contraceptive agent for human use. However, at present its use is limited by the
      practical constraint of determining the day of ovulation for an LH + 2 day
      administration of the drug as indicated from experimental and clinical studies.
      The aim of the present study was to identify the effective period of luteal phase
      (luteal phase window) when a single administration of mifepristone would induce
      antinidatory activity without disturbing menstrual cyclicity and ovulatory
      pattern in the rhesus monkey. RU 486 (2 mg/kg body weight in benzyl
      benzoate/olive oil, 1:3) was given to mated monkeys (n = 9) on cycle day 16 in
      the first treatment cycle (treatment group T1, n = 9), and in the following cycle
      on cycle day 20 (treatment group T2, n = 8). A single s.c. injection of this
      antiprogestin during early to midluteal phase (days 1-10 after ovulation, as
      determined from retrospective analysis of serum concentrations of estrogen and
      progesterone) provided a one hundred per cent protection against pregnancy, with
      no apparent side effects. There were no changes in cycle lengths (F = 3.5; P <
      0.3), day of ovulation (F = 1.8; P < 0.7) and duration of menses (F = 3.5; P <
      0.3) compared with the pre-treatment and post-treatment cycles. Pooled analyses
      of serum concentrations of estrogen and progesterone during luteal phases of T1
      and T2 cycles also showed no variations with those in pre- and post-treatment
      cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132239
TI  - Plasticity of hippocampal and motor cortical pyramidal neurons induced by self
      stimulation experience.
AB  - The self-stimulation (SS) induced neuronal plasticity was observed in CA3
      hippocampal and layer V motor cortical pyramidal neurons. SS experience was
      allowed daily for a total of 1 hour for 10 days through four bipolar electrodes
      implanted bilaterally in lateral hypothalamus (LH) and substantia nigra-ventral
      tegmental area (SN-VTA) in adult male Wistar rats. Examination of pyramidal
      neurons stained by rapid Golgi technique was made in a total of 1,600 neurons out
      of 80 rats consisting of 4 groups. The dendritic intersections were quantified
      upto 200 and 120 microns radial distances in apical and basal dendrites
      respectively. The CA3 hippocampal and layer V motor cortical pyramidal neurons of
      SS group revealed significant increase (P < 0.001, two-way ANOVA) in dendritic
      intersections in both apical and basal dendrites, compared to normal control
      (NC), sham control (SH) and experimenter-administered (EA) group of animals.
      These results demonstrate that SS experience promotes increase in dendritic
      length in hippocampal and motor cortical pyramidal neurons.

PMID- 8132240
TI  - Energy expenditure and ventilatory responses during Siddhasana--a yogic seated
      posture.
AB  - Reports of energy expenditure and ventilatory responses to yogic seated posture
      of Siddhasana are lacking in literature. Various cardio-ventilatory responses
      were studied in states of the horizontal supine, chair-sitting and Siddhasana. It
      was observed that sitting in Siddhasana posture was characterised by greater
      minute ventilation, larger tidal volume, higher oxygen consumption, greater CO2
      elimination, higher heart frequency greater oxygen pulse and lesser as compared
      with other two postures. These observations suggest that Siddhasana is a mild
      type of exercise and may have its application in conditions of low cardio
      respiratory reserves especially in individuals in whom heavy exercises are contra
      indicated.

PMID- 8132241
TI  - Serum level of iron and transferrin in pregnancy and postpartum period.
AB  - This study presents a composite picture of haemoglobin (Hb), serum level of iron
      (SI), total iron binding capacity (TIBC) and percent iron saturation of
      transferrin in women during different trimesters of pregnancy and postpartum
      period. The results were correlated with age and parity. A total of 75 subjects,
      15 from each trimester and 15 postpartal, were studied and compared with 15
      nonpregnant normal subjects. Signs of increased iron demand, increased iron
      turnover and obvious iron deficiency, were demonstrated throughout pregnancy, by
      decrease in haemoglobin, SI, percent iron saturation of transferrin and increased
      TIBC; especially in older age group and multigravidae. SI, TIBC and percent iron
      saturation of transferrin are more sensitive indices of iron status and provide
      us an opportunity to replenish iron stores of an iron deficient pregnant mother
      at an earlier date thus preventing anaemia.

PMID- 8132242
TI  - Involvement of adenosine in postictal events in rats given electroshock.
AB  - The effect of a selective adenosine antagonist, 8-cyclopentyl 1,3
      dimethylxanthine (8-CPT) was used to examine involvement of adenosine in ictal
      and postictal events in rats subjected to maximal electroshock (MES). MES induces
      the ictal event of hindlimb tonic extension (HLTE) followed by postictal
      depression (PID). 8-CPT 10 mg/kg, ip produced maximal significant reduction of
      PID without affecting HLTE, further confirming involvement of adenosine in PID.
      Carbamazepine and sodium valproate were studied independently and were
      coadministered with 8-CPT to determine if their anticonvulsant activity was
      modulated by adenosine and if they altered PID. 8-CPT did not antagonize the
      seizure protection afforded by CBZ or SV. CBZ significantly reduced postictal
      events whereas SV had no significant effect. These observations further confirm a
      role for adenosine in postictal phenomena.

PMID- 8132243
TI  - Dihydropyridine group of calcium channel antagonist in epilepsy.
AB  - Effects of intraperitoneally administered dihydropyridine calcium channel blocker
      nifedipine (NIF) 5 mg/kg and diphenylhydantoin (DPH) 5 mg/kg were studied on
      hippocampal kindling and maximum electro shock thresholds (MEST). All the NIF
      injected rats showed complete suppression of behavioral seizure after the 3rd
      injection. Few of the DPH rats had increased epileptic activity for two days and
      others--absence of Grade--5 seizure after the 5th DPH injection. However, all
      showed partial seizure suppression subsequently. Neither NIF nor DPH could
      suppress the after discharge (AD). MEST were not affected by NIF although DPH
      showed a complete suppression of posterior limb extensor tone in all the rats.

PMID- 8132244
TI  - A BASIC program for teaching membrane potential.
AB  - A qualitative discourse on membrane potential, albeit simple, may be equivocal at
      crucial points while a purely mathematical treatise on the subject, for all its
      exactitude, may be incomprehensible to a student of Physiology. A quasi
      quantitative approach has therefore been attempted as a compromise between
      clarity and exactness. A BASIC program is utilised to compute the stereotype
      calculations and to give instant displays of the results through figures and
      graphic animations.

PMID- 8132245
TI  - Recent advances in the chemotherapy of AIDS.
AB  - Acquired immunodeficiency syndrome (AIDS) continues to grow unabated and in
      pandemic proportions around the world. The complexity and high mutational ability
      of the etiologic agent, human immunodeficiency virus, has posed an unprecedented
      threat toward the chemotherapy of AIDS. Use of contemporary virology to unfold
      the mystery of HIV-1 and the discovery of key molecular targets for
      chemotherapeutic intervention has accelerated the quest for safe and effective
      anti-HIV agents. The vital stages in viral replication amenable to inhibition by
      novel chemical entities and representative examples from diverse chemical classes
      as potential anti-AIDS agents are presented in this review.

PMID- 8132246
TI  - Effect of duration of stress on pain threshold in rats.
AB  - Rats were subjected to immobilization stress of varying duration and their pain
      thresholds were recorded. It was seen that stress of lesser duration did not
      affect the endogenous opioid analgesic system while stressor of longer duration
      stimulated this system to its maximum irrespective of further increasing the
      duration of the stress condition even upto two fold.

PMID- 8132247
TI  - The rate and degree of food compensation on alteration of its caloric density in
      rats.
AB  - The ability to regulate energy level by male albino rats on administration of
      food with varying caloric densities, was studied. The animals fed different
      caloric density diets exhibited marked variations in their caloric in take in the
      initial stages which stabilized after 5 to 10 days and maintained on lower mean
      caloric intake on diet having density of 2.63 Kcal/gm, and higher mean caloric
      intake on diet with density of 4.88 Kcal/gm. Similar variations in body weight
      were also evident with failure to maintain the body weight with caloric dilution.

PMID- 8132249
TI  - Effect of lead exposure on plasma phenylbutazone levels in rats.
AB  - The effect of lead exposure on phenylbutazone kinetics was studied in rats. The
      biological half-life (t1/2) of phenylbutazone was determined from the plasma
      level versus time curve in 3 groups of rats given (i) 10 mg/kg lead orally for 8
      weeks (ii) 100 mg/kg single oral dose and (iii) no lead, after oral
      administration of 100 mg/kg phenylbutazone to all rats. The t1/2 of the drug was
      found to be 33% lower on chronic lead exposure and 46% higher on acute exposure
      than in unexposed control rats. This variation in the t1/2 values of the two
      different groups of rats indicates that probably phenylbutazone metabolism varies
      with the period of lead exposure.

PMID- 8132248
TI  - Effect of variable low doses of aspirin on platelet functions.
AB  - The effect of chronic administration of variable low doses of Aspirin was studied
      on platelet adhesiveness, platelet count, bleeding time and clotting time to find
      out as to how low the dose of aspirin needs to be in order to have an effective
      antiplatelet effect in patients who require such therapy. A statistically
      significant reduction in the platelet adhesiveness was observed in all the
      groups, but the best effect was exhibited by 50 mgm of aspirin dose. Bleeding
      time was also increased in all the groups but statistically significant
      difference was observed with 50, 75 and 100 mgm doses. There was no change in
      platelet count and clotting time.

PMID- 8132250
TI  - Influence of methanol on the release of dopamine from rat brain slices--an in
      vitro study.

PMID- 8132251
TI  - ECG changes in asymptomatic healthy males.

PMID- 8132252
TI  - Hepatitis C virus (HCV) infection in pediatric practice.

PMID- 8132253
TI  - Adverse drug reactions in pediatrics with a study of in-hospital intensive
      surveillance.
AB  - A two-part prospective study of adverse drug reactions (ADRs) in Indian children
      was carried out at a teaching general hospital. Using an in-hospital intensive
      surveillance scheme (IISS) for the detection of ADRs, indoor patients of one of
      the two units in the pediatric ward were monitored daily for 6 months, with the
      other unit serving as a control group. A total of 347 patients were monitored,
      2781 daily orders written and 24,474 doses of 96 different drugs given. Six
      patients suffered from ADRs (1.73%), and 1 reaction proved fatal (0.29%), while
      the control group reported only 1 ADR in the same time period. The frequency of
      ADRs (p < 0.001) and their resultant mortality in Indian children was less than
      that in a western prototype study. Though IISS showed a marked increase in ADR
      reporting, it was too cumbersome for routine use in our country. In the second
      part of the study, 40 cases of ADRs seen over 2 years were analyzed.
      Antimicrobials, especially sulphonamides, accounted for a high percentage of
      cases mostly as skin rashes and fairly severe reactions were common. Patients on
      anti-tuberculous and anti-convulsant drugs required prolonged supervision for
      late onset reactions.

PMID- 8132254
TI  - Dermatoglyphics in congenital profound sensorineural hearing loss: a disease
      marker?
AB  - A dermatoglyphic profile was carried out in 108 cases of congenital profound
      sensorineural hearing loss (SNHL) with delayed development of speech and language
      (DDSL). Rolled finger prints and palmar patterns were obtained by the ink method
      and analysed by the Galton system. In the genetic group (Group A) triradii 6 was
      present whereas it was absent in the nongenetic (Group B) group and their
      controls (p < 0.001). Loop pattern in interdigital areas did not vary
      significantly from controls. The average 'atd' angle in Group A was 41 degrees
      and that in the Group B was 46 degrees (p > 0.5). Ulnar loops predominated over
      the radial loops. Absence of CPW on thumbs of Group A was noted. Total ridge
      count in the Group A was 98.84 and 109 in the Group B (p < 0.05). It was observed
      that no definite pattern existed in a constant fashion and it also exhibited a
      great degree of variation, hence their role in detection of hearing loss is
      questionable.

PMID- 8132255
TI  - Dental caries and periodontal diseases among urban, rural and tribal school
      children.
AB  - The oral health status in school children of Wardha was studied to find out the
      geographical differences in oral health status and to relate it with the teeth
      cleaning habit and nutritional status. A cluster sample of 778 children studying
      in 2 urban, 4 rural and 2 tribal primary schools was selected. Majority (60.8%)
      of children were habituated to clean their teeth with Manjan. The prevalence of
      periodontal diseases was significantly high in children habituated to ash, Manjan
      and coal. The tribal children showed a better oral health status than urban
      counterparts. Nutritional status has played no role in dental decay. The school
      oral health education campaigns should be addressed to dental caries, periodontal
      diseases and the harmful teeth cleaning materials.

PMID- 8132256
TI  - Profile of accidents in children.
AB  - Out of 5031 children admitted to S.N. Hospital, Agra during one year, there were
      716 cases (14.2%) of accidents. Most cases were in the age group of 4-9 years;
      boys were affected more commonly than girls. The maximum cases occurred due to
      fall (44.4%), followed by road traffic accidents (26.4%) and burns (11.5%). The
      consequences in terms of morbidity and mortality was also high. Kerosene oil
      ingestion was the most common encountered form of poisoning. Incriminating
      environmental factors could be identified in 51.8% cases and included poorly
      protected roofs (23.7%), poor state of roads (10.0%), defective vehicles (7.5%),
      and houses opening directly on the streets (7.3%). More than half of the
      accidents took place at home (58.7%), followed by those on streets (30.3%) or at
      farmhouses (57%). Injuries caused by sharp and blunt objects were more common in
      villages. Only 21.4% children had received first aid, often by the family, before
      reaching the hospital. The overall mortality rate was 53.1/1000, but in cases of
      burns the mortality was (146.3/1000). This study suggests that falls and traffic
      accidents have the highest incidence and mortality in childhood accidents and
      modification of the home environment can be an effective measure to prevent such
      incidents.

PMID- 8132257
TI  - Maternal and perinatal mortality due to eclampsia.
AB  - Forty-four mothers with eclampsia and their newborns managed during the year 1988
      at the University Hospital of Banaras Hindu University, Varanasi were analyzed.
      The incidence of eclampsia was 2.2% of all hospital deliveries. Eclampsia was
      more common in women (below 20 years) and at gestation of 36 weeks and below, and
      amongst the mothers deprived of antenatal care. The maternal mortality amongst
      cases of eclampsia was 31.8% and perinatal loss was 38.6%. A relatively high
      incidence of eclampsia and maternal and perinatal loss was considered to be
      related to lack of antenatal care and late referral to the hospital. Our findings
      suggest that more frequent use of properly timed cesarean section can improve the
      maternal outcome.

PMID- 8132258
TI  - Desferrioxamine induced urinary iron excretion in thalassemia.
AB  - Twenty one children of beta thalassemia major aged between 2 and 14 years of age
      on regular blood transfusion were given subcutaneous desferrioxamine. Their serum
      ferritin, 24 hours baseline urinary iron excretion and subcutaneous
      desferrioxamine induced urinary iron excretion were measured. The result showed a
      close correlation between serum ferritin and amount of blood transfusions
      received by the patient. There was good correlation between serum ferritin and
      desferrioxamine induced urinary iron excretion. A negative iron balance could be
      achieved in 15 out of 21 children with one dose of desferrioxamine therapy.

PMID- 8132259
TI  - Zinc supplementation in protein energy malnutrition.
AB  - A pair-matched controlled study was done with 30 children (15 males, 15 females)
      of mild to moderate PEM in test and equal number in control groups, aged 8-24
      months old. At the beginning, in both test and control groups parents were
      advised to provide sufficient amount of home cooked foods so that the child
      received on an average 100-150 Kcal/kg/day of energy and 2-3 g/kg/day of protein.
      Vitamin supplements were provided to all children in both groups. In addition,
      the test group received a supplementation of 5.625 mg of elemental zinc daily
      orally while controls received a placebo. Evaluation at the end of 3 months
      showed that children in test group had a weight gain of 3.742 +/- 0.488 kg
      against 2.035 +/- 0.383 kg of the control group. Similarly, weight velocity was
      5.752 +/- 0.818 g/kg/day in test group against 3.153 +/- 0.617 g/kg/day of the
      control group. These differences in weight gain and weight velocity were highly
      significant (p < 0.001). Serum zinc levels, initially and at the end of study
      were 87.5 +/- 9.6 micrograms/dl and 121.0 +/- 10.1 micrograms/dl, respectively in
      test group in comparison to 91.2 +/- 9.8 micrograms/dl and 91.0 +/- 10.1
      micrograms/dl in controls. This difference was also highly significant (p <
      0.001). The daily total calorie intake remained comparable in both groups. Our
      observations suggest that zinc supplementation during nutritional rehabilitation
      of mild to moderate PEM hastens the recovery.

PMID- 8132260
TI  - Three-year experience with neonatal ventilation from a tertiary care hospital in
      Delhi.
AB  - Ninety neonates were ventilated over a period of 33 months of whom 50 (55.5%)
      survived. Fifty seven babies received IPPV while 33 CPAP. IPPV mode was being
      used more frequently recently and survival rates have steadily improved over past
      3 years. Survival was cent per cent in babies above 1.5 kg on CPAP mode while
      16/26 (57.7%) survived on IPPV mode. Of 22 extremely VLBW (< 1 kg) babies, six
      survived. HMD was the commonest indication of ventilation (50%), of which 53%
      (24/45) survived. The other important indications of ventilation were apnea in 13
      and transient tachypnea in 11 babies. All babies requiring ventilation for
      transient tachypnea survived. Nosocomial infections were common in association
      with ventilation 34/90 (37.7%), out of which in 14 was responsible for about a
      third of deaths. Pulmonary air leaks developed in 12 babies of which 6 died. Two
      babies developed BPD and one ROP. Neonatal ventilation should be ventured in
      centres where basic facilities for level II care already exist. It may not be
      cost effective to ventilate extremely low birth weight neonates.

PMID- 8132261
TI  - Hemoglobin H disease--a report of five cases.

PMID- 8132262
TI  - Screening for dental diseases.

PMID- 8132263
TI  - Pyknodysostosis.

PMID- 8132264
TI  - Pycnodysostosis.

PMID- 8132266
TI  - Thanatophoric dwarfism.

PMID- 8132265
TI  - Sprengel's deformity with absent ribs.

PMID- 8132267
TI  - Typhoid fever before two years of age.

PMID- 8132268
TI  - Diabetes mellitus and pancreatitis as a complication of L-asparaginase therapy.

PMID- 8132269
TI  - Congenital chloride diarrhea.

PMID- 8132270
TI  - Pyogenic psoas abscess in a young infant.

PMID- 8132271
TI  - Exposure to rabies in school precincts: history repeats itself.

PMID- 8132272
TI  - Positioning of the lower limbs in acute paralytic poliomyelitis.

PMID- 8132273
TI  - Theophylline infusion for prevention of apnea of prematurity.

PMID- 8132274
TI  - Nasopharyngeal choristoma.

PMID- 8132275
TI  - Giant congenital melanocytic nevi.

PMID- 8132276
TI  - Esophagopleural fistula complicating suppurative lung disease.

PMID- 8132277
TI  - Towards the conquest of RH hemolytic disease.

PMID- 8132278
TI  - Why breast feed?

PMID- 8132279
TI  - Pediatric AIDS: an Indian perspective.

PMID- 8132280
TI  - Polymorphonuclear leukocyte functions in children with cyanotic and acyanotic
      congenital heart disease.
AB  - Eighteen cyanotic congenital heart disease (CCHD) and 17 acyanotic congenital
      heart disease (ACHD) patients in the age range of 2 months to 10 years along with
      their age and nutrition matched controls were studied for bactericidal,
      chemotactic and phagocytic functions. Bactericidal and phagocytic functions were
      significantly depressed in CCHD (p < 0.001) as well as ACHD group (p < 0.001)
      compared with controls. Chemotactic function was not significantly affected in
      either. Arterial oxygen content (as a measure of hypoxia) was calculated for each
      patient and correlated with each immune parameter by univariate linear regression
      analysis. In CCHD patients linear correlation of borderline significance (p =
      0.07) was found between arterial oxygen content and bactericidal activity, but no
      correlation could be established with phagocytic and chemotactic functions. No
      correlation was obtained between hematocrit and any of the immune parameters. In
      ACHD patients no correlations were obtained between the immune parameters and
      arterial oxygen content or hematocrit. Iron deficiency anemia, known to affect
      bactericidal function, did not seem to affect the immune parameters in CCHD and
      ACHD groups. Altered oxygen content of the blood owing to hypoxia in CCHD
      patients may be an important etiological factor in the genesis of bacteremia and
      cerebral abscess. The affection of immune functions in ACHD cannot be adequately
      explained.

PMID- 8132281
TI  - Altered T and B lymphocytes in multitransfused patients of thalassemia major.
AB  - T and B lymphocytes were estimated in 25 patients with Thalassemia major to
      evaluate their immune status. The percentage of T cells was significantly reduced
      (p < 0.001) while that of B cells was significantly raised (p < 0.001) in
      patients of thalassemia major as compared to age and sex matched controls.

PMID- 8132282
TI  - Cell mediated immune responses in BCG vaccinated children.
AB  - The immunological status of BCG vaccinated and unvaccinated healthy children was
      evaluated to assess the efficacy of BCG. The duration of immunity conferred by
      the vaccine was also investigated. Of the 326 children studied, 170 (52%) had the
      BCG scar and only 24 (14%) showed a positive Mantoux response. Among the
      unvaccinated group, 14 of 156 (9%) showed a positive response. All cases had
      normal proportions of T and B cells in the peripheral blood. The mean values of
      the leukocyte migration inhibition (LMI) test with PHA were also normal. The per
      cent LMI values against PPD were compared in the children classified into groups
      based on their vaccination status and response to Mantoux test. A higher number
      of the vaccinated children had positive LMI values compared to those unvaccinated
      (p < 0.01). The LMI values of children classified into three age groups decreased
      significantly (p < 0.01) with increase in age. Hence, BCG seems to afford some
      protection in children and has to be administered at birth. Revaccination at the
      age of eight years, may boost the waning immunity and, may be considered in this
      age-group.

PMID- 8132283
TI  - An epidemic of encephalitis in Haryana: serological evidence of Japanese
      encephalitis in a few patients.
AB  - An epidemic of encephalitis occurred in the eastern, paddy growing districts of
      Haryana state between July and November 1990. One hundred and eighty-two patients
      with encephalitis were admitted to different hospitals in Haryana and 118 of them
      expired (mortality rate 64.8%); 88% of the patients were children. The male to
      female ratio was 2. 3. 1. IgM class of antibodies to Japanese Encephalitis (JE)
      Virus could be demonstrated in the CSF and/or sera of 3 surviving and 2 fatal
      patients of the 19 patients studied. This is the first detailed report on an
      epidemic of encephalitis in North-Western part of India. Serologically proven
      cases of JE are being reported, for the first time, from this region.

PMID- 8132284
TI  - Successful treatment of hospital acquired Klebsiella pneumoniae meningitis in a
      neonate with ciprofloxacin.

PMID- 8132285
TI  - Angiomatoid malignant fibrous histiocytoma.

PMID- 8132286
TI  - Pulmonary alveolar phospholipoproteinosis.

PMID- 8132287
TI  - Inflammatory linear verrucous epidermal nevus.

PMID- 8132288
TI  - Cystic kidneys in tuberous sclerosis.

PMID- 8132289
TI  - Precocious puberty, gelastic seizures and hypothalamic hamartoma.

PMID- 8132290
TI  - Straight line sign in patent ductus arteriosus.

PMID- 8132291
TI  - Primary Ewing's sarcoma of the orbit.

PMID- 8132292
TI  - Radiological assessment in thymolipoma.

PMID- 8132293
TI  - Role of viruses as causal agents of sporadic infantile diarrhea in calcutta.

PMID- 8132294
TI  - Adverse drug reaction monitoring of ciprofloxacin.

PMID- 8132295
TI  - Unusual foreign body (stone) in the esophagus of a neonate mimicking
      tracheoesophageal fistula.

PMID- 8132296
TI  - Extracorporeal membrane oxygenation for neonatal cardiorespiratory failure.

PMID- 8132297
TI  - Vascular ectasias and diverticulosis. Common causes of lower intestinal bleeding.
AB  - Lower intestinal bleeding is an important medical problem frequently responsible
      for hospital admission in the United States. The two most common causes of this
      type of bleeding are colonic diverticula and vascular ectasias. Because ectasias
      are difficult to diagnose and because many older individuals have asymptomatic
      diverticula, it is often impossible to be certain that one of these lesions is
      the source of blood loss in a given patient. Fortunately, bleeding from an
      ectasia or a diverticulum usually stops spontaneously. A conservative approach to
      therapy, therefore, is strongly recommended. Should a careful evaluation fail to
      reveal the source of bleeding and treatment become necessary because of recurrent
      hemorrhage, the patient should undergo an elective right hemicolectomy. The
      extent of resection is not altered by the presence of diverticulosis in the left
      colon.

PMID- 8132299
TI  - Less frequent causes of lower gastrointestinal bleeding.
AB  - In the United States, four diseases account for the vast majority of cases of
      lower intestinal bleeding: arteriovenous malformation, diverticulosis, neoplasms,
      and internal hemorrhoids. In this article the authors discuss less frequent
      causes of gastrointestinal bleeding. "Common" less frequent causes of
      gastrointestinal bleeding include solitary rectal ulcer syndrome, colonic
      varices, mesenteric vascular insufficiency, small bowel diverticula, Meckel's
      diverticulum, aortoenteric fistula, vasculitis, small intestinal ulceration,
      endometriosis, radiation-induced injury, and intussusception. Less frequent
      causes of gastrointestinal bleeding that have been recently described include
      portal colopathy, diversion colitis, and gastrointestinal bleeding in runners.

PMID- 8132298
TI  - The role of the radiologist in the management of gastrointestinal bleeding.
AB  - The purposes of this article are to clarify the current status of barium studies,
      radionuclide scans, and arteriography in the diagnosis and management of the
      bleeding patient; to provide one interventional radiologist's approach to the
      diagnosis and management of both upper and lower gastrointestinal tract
      hemorrhage in the adult population, incorporating both radiologic and
      nonradiologic techniques; and to review the diagnosis and management of several
      less frequent causes and special categories of bleeding, such as that associated
      with portal hypertension.

PMID- 8132300
TI  - Occult gastrointestinal bleeding.
AB  - Occult gastrointestinal bleeding is loss of blood into the digestive tract that
      is not apparent to the patient or physician by physical examination. It is
      detected by examination of the stool for chemical evidence of blood by laboratory
      techniques or by the observation of iron deficiency. The presence of occult blood
      is important because it may indicate otherwise asymptomatic gastrointestinal
      neoplasia, assist with the evaluation of gastrointestinal symptoms in the absence
      of visible bleeding, and point toward a digestive tract source of blood loss in
      the patient with iron-deficiency anemia.

PMID- 8132301
TI  - Small intestinal bleeding.
AB  - Bleeding from the small intestine may be difficult to diagnose, because of the
      organ's length and free intraperitoneal location. Although there is a variety of
      causes of intestinal bleeding, angiodysplasia is the most common. Several
      different tests can be used to identify the bleeding site preoperatively or
      intraoperatively, including enteroscopy.

PMID- 8132302
TI  - Gastrointestinal bleeding in infancy and childhood.
AB  - In summary, the causes of GI bleeding in infancy and childhood are varied,
      ranging from congenital and hereditary disorders to those more commonly seen in
      the adult population. Many causes of GI bleeding in the pediatric population are
      restricted to a narrow range regarding age of onset, frequently enabling the
      physician to narrow the differential diagnosis before proceeding with invasive
      investigation; however, GI bleeding may involve any portion of the intestinal
      tract, from mouth to anus, as in adulthood, and many causes common to the adult
      population also must be considered.

PMID- 8132303
TI  - AO/ASIF self-tapping screws (STS).

PMID- 8132304
TI  - Cannon Street rail disaster--lessons to be learned.
AB  - We studied the types and mechanisms of injury suffered by passengers involved in
      the Cannon Street rail crash, by a telephone and postal survey of all passengers
      attending St Bartholomew's Hospital for treatment of their injuries, and
      retrospective examination of their hospital records. There were 104 patients of
      whom 91 had complete data sets. Of the 91 patients included in the study, 63 (69
      per cent) had suffered craniofacial trauma. Of the 63 patients with this type of
      injury, 50 had been standing at the time of impact and 48 of these were able to
      say exactly how they had sustained their injuries. Of these 48 passengers, 34
      said that they had collided with the luggage racks (71 per cent). Of the 32
      passengers who had been seated at the time of impact, only 13 sustained
      craniofacial injuries and none had hit the luggage racks (P = 0.0001).
      Craniofacial trauma was the commonest type of injury. Those patients who suffered
      these injuries were most likely to have been standing at the time of impact and
      to have sustained their injuries following collision with a luggage rack. The
      type of luggage racks on this train were particularly dangerous and we recommend
      that the internal design of new British Rail rolling stock addresses this
      problem. This specific recommendation is in support of the more general measures
      discussed in the recently published official report of the incident. In the
      meantime, we consider that passengers should be advised to remain seated until
      trains have come to a halt.

PMID- 8132305
TI  - Non-union of the scaphoid: early and late management.
AB  - The natural history of the fractured scaphoid and its non-union are incompletely
      understood. Papers are not easily compared without a system of classification.
      Avascular necrosis is rarely a problem. Unstable fractures should be fixed early
      to avoid established non-union. Treatment of non-union by graft alone requires
      prolonged immobilization. Non-union is well treated by grafting and internal
      fixation. Carpal collapse should be sought and corrected.

PMID- 8132306
TI  - Gamekeeper's thumb: a quantitative evaluation of acute surgical repair.
AB  - A consecutive series of patients who underwent operation for acute rupture of the
      ulnar collateral ligament of the thumb during a 3 year period from 1985 to 1988
      at the Royal Infirmary of Edinburgh were identified. In total 44 patients
      sustained this injury of whom 19 were available for clinical assessment. The
      minimum period of follow-up was 17 months (mean 32 months). All patients were
      satisfied although six had minor symptoms of discomfort. There were no failures
      of repair; all repaired ligaments were considered to be clinically taut. A
      quantitative evaluation demonstrated all had good restoration of pinch grip.

PMID- 8132307
TI  - Outcome of war-injured patients treated at first aid posts of the International
      Committee of the Red Cross.
AB  - This study describes the effects of 'echelons' on the outcome of victims of the
      Afghan internal armed conflict in terms of mortality and drain of surgical
      resources. A group of 1127 victims of war treated at ICRC first aid posts (FAPs)
      and subsequently referred to a surgical hospital of the International Committee
      of the Red Cross (group A), and a group of 596 victims who were transported
      directly from the area where the injury occurred to the hospital (group B) were
      analysed retrospectively. Mortality in patients treated initially at a FAP and
      admitted within 6-24 h after injury was slightly lower than in patients admitted
      directly. The number of surgical interventions was higher in patients initially
      treated at the FAP. Notably, patients belonging to group A with gunshot injuries
      underwent operation more often than those belonging to group B. No differences
      were found in relation to the incidence of fever, number of units of blood
      transfused and average stay in hospital. The study shows that initial treatment
      at a FAP had no significant influence on the prognosis of the injured. Presumably
      the best ways to improve the prognosis of the victims of war are to train local
      people in first aid, to support locally existing medical facilities and to
      establish an evacuation system in order to support these first aiders and medical
      facilities.

PMID- 8132308
TI  - The prevention of infection in open fractures: an experimental study of the
      effect of fracture stability.
AB  - An experimental model of a contaminated open fracture has been developed. This
      model has been used to test the hypothesis that stable fixation of a contaminated
      open fracture will reduce its susceptibility to infection. The tibiae of male New
      Zealand white rabbits were fractured and then fixed with either a dynamic
      compression plate (stable group) or a loose-fitting intramedullary rod (unstable
      group). The fracture site was then inoculated with a standard inoculum of
      Staphylococcus aureus. There were 20 rabbits in the stable group and
      osteomyelitis developed in seven (35 per cent); in the unstable group 15 (71 per
      cent) out of 21 animals developed osteomyelitis. This difference in infection
      rates was statistically significant (P < 0.02). This experimental study supports
      the concept of stabilization of open fractures in man.

PMID- 8132309
TI  - Heel pad thickness following calcaneal fractures: ultrasound findings.
AB  - Ultrasound measurements of heel pad thickness in 21 patients who had suffered
      unilateral fractures of the calcaneum were taken. Body weight was also recorded.
      Contrary to previous assertions in the literature, heel pad thinning was not
      found to occur and in fact a significant increase in heel pad thickness on the
      affected side was noted.

PMID- 8132310
TI  - Low-contact dynamic compression plating of the clavicle.
AB  - Internal fixation of the clavicle is rarely necessary. When it is warranted, the
      clavicle's complex three-dimensional morphology and functional anatomy, proximity
      to vital structures, and the multidirectional biomechanical forces acting upon it
      place considerable demands on any implant used for skeletal fixation. We treated
      nine clavicles with the recently-introduced 3.5 mm low contact-dynamic
      compression plate (LC-DCP). Surgery was performed for symptomatic non-union in
      six patients, shoulder dysfunction following a malunited fracture in one, for an
      open fracture in one, and for an acute fracture associated with brachial plexus
      injury in one. After an average follow-up period of 17 months union was secured
      in each case. The advantages afforded by the 3.5 mm LC-DCP in internal fixation
      of the clavicle with its uniquely demanding anatomical and biomechanical
      characteristics are discussed.

PMID- 8132311
TI  - Bony injuries in association with minor head injury: lessons for improving the
      diagnosis of facial fractures.
AB  - One hundred consecutive admissions for minor head injury over a 12-week period in
      1992 were analysed for all associated bony injuries. Fractures of the facial
      bones were found to be the commonest concurrent injury. A number of these were
      missed in the Accident and Emergency Department either due to inadequate
      radiographic views or incomplete recognition of clinical and radiological
      findings. A protocol for assessment of injury to the head and face is suggested.

PMID- 8132312
TI  - The effect of thread length and location on extraction strengths of iliosacral
      lag screws.
AB  - Although iliosacral lag screws are an established technique for fixation of
      sacroiliac joint dislocation and sacral fractures, there is a paucity of data on
      the relative strength of fixation of screws in the sacral ala and body. The
      purpose of this study was to quantify and compare the extraction strength of
      cancellous screws in the sacral ala and body. Twelve fresh frozen cadaveric human
      pelves (mean age 76) were used to test the extraction strength of three groups of
      7.0 mm cannulated cancellous screws: long-threaded in the sacral body, short
      threaded in the body and short-threaded in the ala. The mean extraction strengths
      were 925, 374 and 71 newtons (or 92, 37, and 7 kg) respectively. The differences
      between the three groups were highly significant (all P < 0.0025). These data
      strongly recommend that the goal in iliosacral lag screw fixation should be to
      insert a long-threaded screw into the sacral body, if safely feasible. Fixation
      in the ala is inferior and should be avoided in the elderly.

PMID- 8132313
TI  - The effect of kinetic positioning on lung function and pulmonary haemodynamics in
      posttraumatic ARDS: a clinical study.
AB  - In the treatment of adult respiratory distress syndrome (ARDS) no breakthrough
      has been achieved so far. In several cases of severe ARDS in multiply injured
      patients we have seen improvements of lung function by means of continuous body
      positioning. We therefore compared the effect of kinetic positioning (KIN) on
      lung function and haemodynamics in ARDS patients with conventional (CON) supine
      positioning. Pulmonary and systemic haemodynamics were determined on the basis of
      pulmonary artery catheter measurements. On a daily basis oxygenation ratio
      (PaO2/FiO2) and pulmonary shunt (Os/Ot. per cent) were calculated. Extravascular
      lung water (EVLW, ml/kg BW) was determined by the double indicator thermodilution
      technique. Twenty-two patients were included: KIN, N = 11, CON, N = 11. Mortality
      from ARDS in KIN patients was 18.2 per cent (N = 2): in CON patients it was 63.6
      per cent (N = 7). The oxygenation ratio (PaO2/FiO2) increased significantly in
      KIN patients from 140 + 45 (day 0) to 237 + 40 (P < 0.05) (day 5); in CON
      patients no improvement was seen (143 + 48 (day 0). 133 + 44 (day 5); n.s.
      between groups at day 0: P < 0.05 between groups at day 5). Pulmonary shunt
      decreased significantly from 26.6 + 4 per cent (day 0) to 12.5 + 2 per cent (day
      5) (P < 0.05) in KIN patients and was 36.6 + 6 per cent at day 0 and 31.4 + 2 per
      cent at day 5 in CON patients (P < 0.05 between groups at day 5).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8132314
TI  - The management of penile zip entrapment in children.
AB  - Thirty boys, aged 2-12 years, presented with penile zip entrapment to one
      Paediatric Accident and Emergency Department over a 7 year period. The rate of
      presentation was one zip entrapment per 4068 new patient attendances. In contrast
      to previous reports, injuries occurred most commonly whilst the zip was being
      done up and whilst underpants were being worn. Two types of entrapment were seen,
      determining the way in which release was achieved. Contrary to previous
      suggestions, most children (26 out of 30) were easily managed in the Accident and
      Emergency Department without general anaesthetic. No patient required
      circumcision or suffered any sequelae. An algorithm for treatment based upon the
      experience of this study is presented.

PMID- 8132315
TI  - Post traumatic lymphocele.

PMID- 8132316
TI  - Skeletal traction using double Denham pins.

PMID- 8132317
TI  - Cytokine-mediated indoleamine 2,3-dioxygenase induction in response to Chlamydia
      infection in human macrophage cultures.
AB  - The purpose of this study was to characterize further the events leading to the
      metabolic degradation of tryptophan in Chlamydia-infected cultures in the absence
      of added interferon (IFN). Macrophages on coverslips were infected with Chlamydia
      psittaci, and tryptophan decyclization was determined 24 h later by reverse-phase
      high-performance liquid chromatography. Tryptophan metabolites cochromatographed
      with kynurenine and N-formylkynurenine, the end products of tryptophan
      decyclization by the IFN-inducible enzyme indoleamine 2,3-dioxygenase (IDO).
      Although chloramphenicol pretreatment completely inhibited chlamydial
      replication, IDO was stimulated to an extent similar to that in untreated,
      infected cells. No IDO induction was observed in cells pretreated with
      cycloheximide even though chlamydial growth was slightly greater than in
      untreated cells. These results indicate that enhanced tryptophan decyclization
      was due to induction of IDO. IDO induction was dependent on the size of the
      chlamydial inoculum. Heat- or UV-inactivated chlamydiae induced significantly
      less IDO activity than viable chlamydiae. Culture supernatants from Chlamydia
      infected macrophages induced IDO activity in a dose-dependent manner, suggesting
      that a secreted product of infected cells was responsible for IDO induction. A
      combination of neutralizing antibodies to IFN-alpha and IFN-beta inhibited
      induction of IDO activity by infected cell culture supernatants. Furthermore, IL
      1 enzyme-linked immunosorbent assay results indicated the accumulation of IL-1
      beta in the culture medium. Thus, induction of IDO in Chlamydia-infected
      macrophages reflects the production of cytokines in response to infection and may
      represent a normal host cell response to control intracellular infection.

PMID- 8132318
TI  - Specificity and function of murine monoclonal antibodies and immunization-induced
      human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas
      aeruginosa serogroup 06.
AB  - Structural and antigenic heterogeneity has been noted among lipopolysaccharides
      (LPS) produced by Pseudomonas aeruginosa within serogroups previously considered
      to be serologically homogeneous. We characterized murine monoclonal antibodies
      (MAbs) and immunization-induced human polyclonal antibodies reactive with one or
      more of five structurally variant LPS subtypes belonging to serogroup 06 of the
      International Antigenic Typing System. Analyses of five different MAbs employing
      purified LPS or whole patterns of subtype specificity, ranging from recognition
      of a single subtype to reactivity with all five. MAb-mediated opsonophagocytic
      killing and in vivo protection against live challenge in mice correlated, in
      general, with differential binding to various LPS subtypes. In comparison, sera
      from human vaccinees immunized with LPS-derived high-molecular-weight
      polysaccharide from P. aeruginosa Fisher immunotype 1, one of five serogroup 06
      subtypes, exhibited LPS binding and opsonic activity against all five subtypes.
      Antibodies in the human sera effectively inhibited binding to all five LPS
      subtype antigens of the cross-reactive MAb, LC3-2H2, suggesting the existence of
      a common serogroup-related epitope. These findings emphasize the importance of
      defining subtype-associated variations in LPS antigenicity and corresponding
      differences in antibody specificity and function as a basis for designing
      immunoprophylactic or therapeutic strategies which target P. aeruginosa LPS.

PMID- 8132319
TI  - Role of polymorphonuclear neutrophil leukocytes and their integrin CD11a (LFA-1)
      in the pathogenesis of severe murine malaria.
AB  - Infection of CBA mice with Plasmodium berghei ANKA results in severe malaria,
      which is characterized by mortality 6 to 10 days after infection and is
      associated with alterations of the brain microcirculation. These alterations
      consist of (i) intravascular sequestration of monocytes, (ii) an increase in
      vascular permeability as documented by Evans blue diffusion, and (iii)
      microhemorrhages. This syndrome may be due to an increase of production of tumor
      necrosis factor alpha which upregulates the endothelial expression of ICAM-1 and
      thus leads to adhesion of CD11a/CD18 (LFA-1)-bearing cells. During severe
      malaria, we found an important sequestration of the CD11a-bearing
      polymorphonuclear neutrophil leukocytes (PMN) in the lung but not in the brain.
      Treatment with a monoclonal antibody (MAb) against PMN, which induces profound
      neutropenia, prevented mortality and Evans blue diffusion in the brain and the
      lung, while it unexpectedly increased the occurrence of microhemorrhages. The
      anti-PMN MAb abolished PMN sequestration in the lung and also partially decreased
      monocyte sequestration in the brain and the lung. Treatment with an anti-CD11a
      MAb also prevented mortality, Evans blue diffusion, and PMN and monocyte
      sequestration. This study shows that PMN contribute to the mortality and the
      microvascular lesions resulting from severe malaria. This may be due to their
      CD11a-dependent sequestration in the lung and also to their indirect influence on
      vascular permeability and the sequestration of monocytes.

PMID- 8132320
TI  - Purification and characterization of a high-molecular-weight outer membrane
      protein of Moraxella (Branhamella) catarrhalis.
AB  - Moraxella (Branhamella) catarrhalis is an important bacterial cause of otitis
      media in children and lower respiratory tract infections in adults. In this
      study, we describe the presence of a novel high-molecular-weight outer membrane
      protein (HMW-OMP). This protein varies from 350 to 720 kDa in apparent molecular
      mass among strains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). The protein was detected on SDS-PAGE in 13 of 14 strains tested. We
      developed a monoclonal antibody and polyclonal antisera to this protein. In
      immunoblot assays, the protein was present in all 14 strains tested. The
      immunoblot assays suggest that the protein has at least one epitope that is
      conserved among strains. A purification method using anion-exchange
      chromatography is described. Treatment of outer membrane preparations and
      purified protein by heat and reducing agents did not change the apparent
      molecular mass of the HMW-OMP. Formic acid treatment of outer membrane
      preparations and purified HMW-OMP produced a single band with an apparent
      molecular mass of 120 to 140 kDa. We postulate that this may be the monomer of an
      oligomeric protein. The HMW-OMP, which varies in molecular mass among strains and
      is antigenically conserved, will be studied further to determine its role in the
      human immune response and may be useful as a marker in studying strain
      acquisition in patients.

PMID- 8132321
TI  - Sequence and expression of the genes for HPr (ptsH) and enzyme I (ptsI) of the
      phosphoenolpyruvate-dependent phosphotransferase transport system from
      Streptococcus mutans.
AB  - We report the sequencing of a 2,242-bp region of the Streptococcus mutants NG5
      genome containing the genes for ptsH and ptsI, which encode HPr and enzyme I
      (EI), respectively, of the phosphoenolpyruvate-dependent phosphotransferase
      transport system. The sequence was obtained from two cloned overlapping genomic
      fragments; one expresses HPr and a truncated EI, while the other expresses a full
      length EI in Escherichia coli, as determined by Western immunoblotting. The ptsI
      gene appeared to be expressed from a region located in the ptsH gene. The S.
      mutans NG5 pts operon does not appear to be linked to other phosphotransferase
      transport system proteins as has been found in other bacteria. A positive
      fermentation pattern on MacConkey-glucose plates by an E. coli ptsI mutant
      harboring the S. mutans NG5 ptsI gene on a plasmid indicated that the S. mutans
      NG5 EI can complement a defect in the E. coli gene. This was confirmed by protein
      phosphorylation experiments with 32P-labeled phosphoenolpyruvate indicating
      phosphotransfer from the S. mutans NG5 EI to the E. coli HPr. Two forms of the
      cloned EI, both truncated to varying degrees in the C-terminal region, were
      inefficiently phosphorylated and unable to complement fully the ptsI defect in
      the E. coli mutant. The deduced amino acid sequence of HPr shows a high degree of
      homology, particularly around the active site, to the same protein from other
      gram-positive bacteria, notably, S. salivarius, and to a lesser extent with those
      of gram-negative bacteria. The deduced amino acid sequence of S. mutans NG5 EI
      also shares several regions of homology with other sequenced EIs, notably, with
      the region around the active site, a region that contains the only conserved
      cystidyl residue among the various proteins and which may be involved in
      substrate binding.

PMID- 8132322
TI  - Protection of gerbils from amebic liver abscess by immunization with a
      recombinant Entamoeba histolytica antigen.
AB  - Amebiasis, infection by the intestinal protozoan parasite Entamoeba histolytica,
      is a leading parasitic cause of death. As a step in the development of a
      recombinant antigen vaccine to prevent E. histolytica infection, we looked at the
      ability of a recombinant version of the serine-rich E. histolytica protein
      (SREHP) to elicit a protective immune response against invasive amebic disease.
      Gerbils, a standard model for amebic liver abscess, were immunized with either a
      recombinant SREHP/maltose-binding protein (MBP) fusion, recombinant MBP alone, or
      phosphate-buffered saline (PBS), all combined with complete Freund's adjuvant. In
      the first trial (group 1), gerbils received a primary and two booster
      immunizations intraperitoneally; in the second trial (group 2), gerbils were
      immunized by a single intradermal injection. SREHP/MBP-immunized gerbils in both
      groups produced antibody to native SHEHP and developed delayed-type
      hypersensitivity responses to recombinant SREHP. All gerbils were challenged by
      an intrahepatic injection with 5 x 10(4) virulent E. histolytica HM1-IMSS
      trophozoites. Complete protection from amebic liver abscess was seen in 64% of
      the SHEHP/MBP-immunized gerbils in group 1 and in 100% of the SREHP/MBP-immunized
      gerbils in group 2. There was no protection observed in MBP- or PBS-immunized
      gerbils in either group. Our results indicate that the SREHP molecule has
      potential as a vaccine to prevent amebic infection and demonstrate that
      successful vaccination of animals with recombinant E. histolytica antigen
      vaccines is possible.

PMID- 8132323
TI  - Binding of lysozyme to lipopolysaccharide suppresses tumor necrosis factor
      production in vivo.
AB  - Endotoxin (lipopolysaccharide [LPS]) released during gram-negative bacterial
      infection induces varieties of cytokines which directly and/or indirectly cause
      shock, disseminated intravascular coagulation, and death. We previously showed
      that lysozyme (LZM) was an LPS-binding protein and inhibited various
      immunomodulating activities of LPS. In this study, we examined the effect of LZM
      on the LPS-triggered septic shock model induced by carrageenan treatment and
      assessed by tumor necrosis factor production. The data presented in this report
      strongly suggest that LZM-LPS complex formation completely abrogates tumor
      necrosis factor production and the mortality caused by LPS and that LZM may be
      useful for the treatment of endotoxin shock.

PMID- 8132325
TI  - Competition between rBPI23, a recombinant fragment of bactericidal/permeability
      increasing protein, and lipopolysaccharide (LPS)-binding protein for binding to
      LPS and gram-negative bacteria.
AB  - Lipopolysaccharide (LPS)-binding protein (LBP) and bactericidal/permeability
      increasing protein (BPI) are two structurally related lipid A-binding proteins
      with divergent functional activities. LBP mediates activation of macrophage and
      other proinflammatory cells. In contrast, BPI has potent bactericidal and LPS
      neutralizing activities. A recombinant fragment of BPI (rBPI23) retains the
      potent biological activities of the holo protein and may represent a novel
      therapeutic agent for the treatment of gram-negative infections, sepsis, and
      endotoxemia. For therapeutic effectiveness in many clinical situations, rBPI23
      will have to successfully compete with high serum levels of LBP for binding to
      endotoxin and gram-negative bacteria. The relative binding affinities of rBPI23
      and human recombinant LBP (rLBP) for lipid A and gram-negative bacteria were
      evaluated. The binding of both proteins to lipid A was specific and saturable
      with apparent Kds of 2.6 nM for rBPI23 and 58 nM for rLBP. rBPI23 was
      approximately 75-fold more potent than rLBP in inhibiting the binding of 125I
      rLBP to lipid A. The binding affinity of rBPI23 (Kd = 70 nM) for Escherichia coli
      J5 bacteria was also significantly higher than that of rLBP (Kd = 1,050 nM). In
      addition, rBPI23 at 0.2 micrograms/ml was able to inhibit LPS-induced tumor
      necrosis factor release from monocytes in the presence of 20 micrograms of rLBP
      per ml. These results demonstrate that rBPI23 binds more avidly to endotoxin than
      does rLBP and that, even in the presence of a 100-fold weight excess of rLBP,
      rBPI23 effectively blocks the proinflammatory response of peripheral blood
      mononuclear cells to endotoxin.

PMID- 8132324
TI  - Induction of early-response genes KC and JE by mycobacterial lipoarabinomannans:
      regulation of KC expression in murine macrophages by Lsh/Ity/Bcg (candidate
      Nramp).
AB  - The murine chromosome 1 gene Lsh/Ity/Bcg (candidate Nramp) regulates macrophage
      activation for antimicrobial activity against Salmonella typhimurium, Leishmania
      donovani, and Mycobacterium spp. To determine early events in the activation
      pathway, the ability of mycobacterial lipoarabinomannan (LAM) to induce early
      gene (KC and JE) expression in macrophages from susceptible (S) C57BL/10ScSn
      (Lshs) and congenic resistant (R) B10.L-Lshr mice was investigated. Stimulation
      with 1.8 microgram of arabinofuranosyl-terminated LAM (AraLAM) per ml resulted in
      similar kinetics for KC or JE expression in S and R macrophages. However, whereas
      JE/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA ratios remained
      equivalent, R macrophages consistently showed enhanced KC/GAPDH ratios within 30
      to 40 min of stimulation compared with S macrophages. Significant differences in
      KC/GAPDH ratios were observed throughout the peak period (0.5 to 6 h) of the KC
      response and with doses of AraLAM ranging from 0.01 to 2.5 micrograms/ml. Heavily
      mannosylated LAM from virulent Mycobacterium tuberculosis Erdman, in doses of up
      to 2.5 micrograms/ml, failed to stimulate KC or JE in S or R macrophages. Gamma
      interferon alone (25 U/ml) stimulated equivalent JE expression in S and R
      macrophages and synergized with AraLAM to enhance JE in both. In contrast, AraLAM
      induced KC expression was inhibited in the presence of gamma interferon.
      Agonist/inhibitor studies were undertaken to determine the signal transduction
      pathways mediating KC expression. The protein kinase C (PKC) inhibitor Calphostin
      C (200 nM) inhibited AraLAM-induced KC by 34% +/- 4% in S macrophages and 43% +/-
      5% in R macrophages; the cyclic AMP-dependent PKA inhibitor KT5720 (2 microM)
      inhibited AraLAM-induced KC by 33% +/- 4% (S) and 25% +/- 5% (R). A role for Ca2+
      was indicated because ionophore alone stimulated KC expression and synergized
      with AraLAM to give a dramatically enhanced response. Induction of KC was also
      inhibited by (i) blocking constitutive nitric oxide (NO) production by
      preincubation of macrophages with NG-monomethyl-L-arginine (400 microM) (48% +/-
      8% [S] and 40% +/- 11% [R]) and (ii) incubation of macrophages with the cyclic
      GMP-dependent kinase inhibitor KT5823 (4 microM) (65% +/- 4% [S] and 72% +/- 6%
      [R]). The manner in which these PKC-, PKA-, and Ca(2+)-dependent, NO-mediated
      cyclic GMP-dependent kinase signal transduction pathways may relate to function
      of the candidate Lsh/Ity/Bcg gene Nramp is discussed.

PMID- 8132327
TI  - Preferential binding of Plasmodium falciparum SERA and rhoptry proteins to
      erythrocyte membrane inner leaflet phospholipids.
AB  - Proteins of an apical organelle, the rhoptry, of Plasmodium falciparum are
      secreted into the host erythrocyte membrane during merozoite invasion. To
      identify the membrane-binding site for rhoptry proteins, we examined the binding
      of parasite proteins to phospholipid vesicles. A specific interaction between the
      rhoptry proteins of 140, 130, and 110 kDa to vesicles containing
      phosphatidylserine and phosphatidylinositol was observed. Both phospholipids are
      preferentially localized on the inner leaflet of the bilayer. Binding to other
      phospholipids, including sphingomyelin, was considerably less. In addition, the
      120-kDa serine repeat antigen known as SERA, which was determined to be present
      on the merozoite, bound to phosphatidylserine vesicles and much less to vesicles
      of other phospholipids. Both the rhoptry and SERA proteins exhibited a preference
      for phosphatidylserine with short acyl side chains. Specific binding of SERA and
      the rhoptry proteins to phospholipids of the inner leaflet of membranes suggests
      a possible mechanism by which the protein facilitate invasion into host cells.

PMID- 8132326
TI  - Tumor necrosis factor as an autocrine and paracrine signal controlling the
      macrophage secretory response to Candida albicans.
AB  - We have previously demonstrated that the hyphal form of Candida albicans (H
      Candida), but not the yeast form (Y-Candida), acts as a macrophage-stimulating
      agent. The early response (1 to 3 h) of the macrophage cell line ANA-1 to H
      Candida results in enhanced tumor necrosis factor (TNF) transcription and
      production. Here we show that when coincubation times are prolonged (3 to 24 h),
      Y-Candida also exhibits stimulatory properties. This phenomenon has been ascribed
      to the occurrence of the dimorphic transition, as demonstrated by microscopic
      evaluation of the cultures and by experiments in which both killed Y-Candida and
      the agerminative strain C. albicans PCA-2 failed to induce cytokine production.
      TNF produced in response to H-Candida acts as an autocrine and paracrine signal
      controlling the macrophage secretory response to C. albicans. In fact, addition
      of anti-TNF polyclonal antibodies to the coculture of ANA-1 macrophages and H
      Candida results in a marked and time-dependent decrease of TNF transcript levels.
      Moreover, pretreatment of macrophages with recombinant TNF for 3 h enhances TNF
      and induces interleukin-1 production in response to both forms of Candida, while
      pretreatment for 18 h renders macrophages refractory to any stimuli.
      Interestingly, the kinetics of interleukin-1 transcription and secretion in
      response to H-Candida are delayed with respect to those of TNF. Overall, these
      data indicate that TNF, produced by macrophages in response to H-Candida,
      regulates its own production as well as that of other soluble factors, thus
      suggesting that this cytokine plays multiple roles in the immune mechanisms
      involved in Candida infection.

PMID- 8132328
TI  - Binding of Yersinia enterocolitica to purified, native small intestinal mucins
      from rabbits and humans involves interactions with the mucin carbohydrate moiety.
AB  - Plasmid-bearing (but not plasmid-cured) Yersinia enterocolitica is known to bind
      to purified small intestinal mucins from rabbits and humans. This study examined
      which region(s) of the mucin molecule is important for bacterial adherence.
      Pronase digestion of mucin and removal of nonglycosylated or poorly glycosylated
      peptide regions had no effect on bacterial binding, suggesting that plasmid
      bearing Y. enterocolitica interacts with mucin carbohydrate. Periodate oxidation
      also did not alter bacterial adherence, indicating that vicinal hydroxyl groups
      in the mucin sugars are not important for binding. Boiling of mucin,
      depolymerization by reduction of disulfide bonds, or removal of noncovalently
      associated lipid actually enhanced bacterial adherence, suggesting that plasmid
      bearing Y. enterocolitica can interact with additional domains in the mucin
      molecule revealed by these treatments. These domains were destroyed by pronase
      digestion. In delipidated mucin (but not in reduced or boiled mucin), binding to
      these domains appeared to be hydrophobic since it could be prevented by treatment
      of bacteria with tetramethyl urea. Oligosaccharides obtained from both human and
      rabbit small intestinal mucins were capable of inhibiting attachment of plasmid
      bearing (but not plasmid-cured) Y. enterocolitica to mucin. After removal of
      terminal and backbone sugar residues by treatment of mucin with
      trifluoromethanesulfonic acid, binding of plasmid-bearing bacteria increased
      significantly when N-acetylgalactosamine, either alone or with galactose
      attached, was revealed, indicating that core regions of the sugar side chains are
      involved in bacterial binding. Adherence of plasmid-cured organisms was
      unaffected by trifluoromethanesulfonic acid treatment of mucin. We concluded that
      virulent Y. enterocolitica interacts with the carbohydrate moiety of native small
      intestinal mucin through a plasmid-mediated process. When mucin becomes
      denatured, binding of the organism can increase through hydrophobic and
      nonhydrophobic interactions with (most likely) the mucin protein.

PMID- 8132329
TI  - Role of human major histocompatibility complex DQ molecules in superantigenicity
      of streptococcus-derived protein.
AB  - Antigenicity of peptic extract from type 12 group A streptococci (PEAST12) for T
      cells was examined in major histocompatibility complex (MHC) class II transgenic
      mice. PEAST12 was mitogenic for murine T cells when antigen-presenting cells were
      obtained from human MHC (HLA)-DQ4 alpha beta transgenic mice or from DQ6 alpha
      beta transgenic mice but was not mitogenic in DR alpha transgenic, DR51 alpha
      beta transgenic, E alpha transgenic, or nontransgenic mice. In addition, PEAST12
      showed mitogenicity for murine T cells in DQ4 alpha singly transgenic mice but
      not in DQ4 beta singly transgenic mice. T-cell stimulation by PEAST12 was
      unrestricted by but dependent on the expression of HLA-DQ molecules on antigen
      presenting cells, and PEAST12 selectively activated T-cell receptor V beta 11-, V
      beta 15-, and V beta 18-positive T cells in mice. We propose that PEAST12
      contains a superantigen which binds preferentially to the alpha-chain of HLA-DQ
      molecules. The well-known phenomenon that peptic extracts from group A
      streptococci are mitogenic in humans but not in mice is likely due to structural
      differences in MHC class II molecules between these two species of mammals.

PMID- 8132330
TI  - Lactoferrin binds to porins OmpF and OmpC in Escherichia coli.
AB  - Lactoferrin (Lf) is an iron-binding antimicrobial protein present in milk and on
      mucosal surfaces, with a suggested role in preimmune host defense. Certain
      strains of Escherichia coli (bacterial whole cells) demonstrate specific
      interaction with 125I-labeled Lf. A band with a mass of approximately 37 kDa,
      which was reactive with horseradish peroxidase-labeled Lf, was identified in the
      boiled cell envelope and outer membrane preparations of an Lf-binding E. coli
      strain, E34663, and a non-Lf-binding strain, HH45, by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting
      (immunoblotting). Such a band was not detected in the unboiled native cell
      envelope and outer membrane preparations. The molecular mass and the property of
      heat modifiability suggested that the Lf-binding proteins were porins. The native
      trimeric form of porin OmpF isolated from strain B6 and its dissociated monomeric
      form both reacted with horseradish peroxidase-labeled Lf and with monoclonal
      antibodies specific for OmpF. Furthermore, by using E. coli constructs with
      defined porin phenotypes, OmpF and OmpC were identified as the Lf-binding
      proteins by urea-SDS-PAGE and Western blotting and by 125I-Lf binding studies
      with intact bacteria. These data establish that Lf binds to porins, a class of
      well-conserved molecules common in E. coli and many other gram-negative bacteria.
      However, in certain strains of E. coli these pore-forming proteins are shielded
      from Lf interaction.

PMID- 8132331
TI  - Genetic regulation of fructosyltransferase in Streptococcus mutans.
AB  - Streptococcus mutans possesses several extracellular sucrose-metabolizing enzymes
      which have been implicated as important virulence factors in dental caries. This
      study was initiated to investigate the genetic regulation of one of these
      enzymes, the extracellular fructosyltransferase (Ftf). Fusions were constructed
      with the region upstream of the S. mutans GS5 Ftf gene (ftf) and a promoterless
      chloramphenicol acetyltransferase (CAT) gene. The fusions were integrated at a
      remote site in the chromosome, and transcriptional activity in response to the
      addition of various carbohydrates to the growth medium was measured. A
      significant increase in CAT activity was observed when glucose-grown cells were
      shifted to sucrose-containing medium. Sucrose-induced expression was repressed
      immediately upon addition of phosphoenolpyruvate phosphotransferase system sugars
      to the growth media. Deletion analysis of the ftf upstream region revealed that
      an inverted repeat structure was involved in the control of ftf expression in
      response to carbohydrate. However, the control of the level of ftf transcription
      appeared to involve a region distinct from that mediating carbohydrate
      regulation. CAT gene fusions also were constructed with the ftf upstream region
      from S. mutans V403, a fructan-hyperproducing strain which synthesizes increased
      levels of Ftf. Sequence analysis of the upstream ftf region in this strain
      revealed several nucleotide sequence changes which were associated with high
      level ftf expression. Comparison of the GS5 and V403 ftf expression patterns
      suggested the presence of a trans-acting factor(s) involved in modulation of ftf
      expression in response to carbohydrate. This factor(s) was either absent or
      altered in V403, resulting in the inability of this organism to respond to the
      presence of carbohydrate. The sequences of the ftf regions from three additional
      fructan-hyperproducing strains were determined and compared with that of V403.
      Only one strain displayed nucleotide changes similar to those of V403. Two
      additional strains did not have these changes, suggesting that several mechanisms
      for up-regulation of ftf expression exist.

PMID- 8132332
TI  - YadA mediates specific binding of enteropathogenic Yersinia enterocolitica to
      human intestinal submucosa.
AB  - The binding of live Yersinia enterocolitica to frozen sections of human intestine
      was investigated qualitatively by monitoring the binding of bacteria by using
      Gram or immunoperoxidase staining as well as quantitatively by a new enzyme
      immunoassay-on-slide method. We have demonstrated that the binding of various Y.
      enterocolitica serotypes and Escherichia coli clones to frozen sections of human
      intestine is mediated by the Yersinia adhesin, YadA. The YadA-mediated binding
      occurs mainly at the submucosal layer of the intestinal wall and only to a
      limited extent at the mucosal layer; there binding is mostly to the mucin
      threads. In addition, partially purified YadA binds to frozen sections with a
      pattern similar to that of intact bacteria. Collagen, laminin, or partially
      purified YadA only partially inhibited the YadA-mediated binding of bacteria,
      presumably because YadA is multifunctional. A combination of collagen and laminin
      inhibited the binding more efficiently. Therefore, YadA may be involved in the
      interactions with the extracellular matrix molecules after the invasion of the
      intestinal tissue.

PMID- 8132333
TI  - Streptococcal M6 protein binds to fucose-containing glycoproteins on cultured
      human epithelial cells.
AB  - M6 protein of Streptococcus pyogenes binds directly to HEp-2 cell surfaces and
      helps to mediate bacterial adhesion. Two epithelial cell receptors for M protein
      were identified as 97- and 205-kDa glycoproteins. Purified recombinant M6 protein
      (rM6) showed a dose-dependent and saturable binding to isolated HEp-2 membranes
      in an enzyme immunoassay. The HEp-2 cell receptors were selectively denatured by
      pretreatment of isolated membranes at 80 degrees C or with chymotrypsin; binding
      activity for rM6 was reduced 83 and 80%, respectively. Pretreatment of the HEp-2
      membranes with neuraminidase-N-glycosidase, neuraminidase-O-glycosidase, alpha-L
      fucosidase, or Ulex lectin caused 33, 42, 73, and 80% reduction of rM6 binding,
      respectively. Quantitative analysis of HEp-2 cells pretreated with alpha-L
      fucosidase showed that the 97- and 205-kDa glycoproteins lost 70 and 62% of their
      abilities to bind M6 protein and that 33% of the HEp-2 cell's ability to bind
      whole streptococci was also lost. These results indicated that binding of M6
      protein to HEp-2 cell surfaces is highly selective for certain fucose-containing
      oligosaccharides on these glycoproteins.

PMID- 8132334
TI  - Role of YadA in resistance of Yersinia enterocolitica to phagocytosis by human
      polymorphonuclear leukocytes.
AB  - Pathogenic Yersinia enterocolitica cells do not induce the chemiluminescence
      response of human polymorphonuclear leukocytes (PMNs). We tested the
      chemiluminescence response to Y. enterocolitica mutants affected in the known pYV
      encoded factors. We did not detect any influence of the Yops in this phenomenon.
      By contrast, the presence of YadA correlated with a lack of chemiluminescence.
      The expression of YadA at the bacterial surface also reduced the phagocytosis by
      PMNs. Finally, we measured the survival of Y. enterocolitica cells confronted
      with PMNs by the classical plating method and by a new luminometry assay. We
      observed that YadA+ bacteria were not killed, while YadA- bacteria were killed.
      We conclude that the presence of YadA at the surface of Y. enterocolitica cells
      prevents phagocytosis and killing by PMNs. This conclusion is in good agreement
      with our recent observation that YadA protects Y. enterocolitica from
      opsonization by C3b.

PMID- 8132335
TI  - Direct effects of metabolic products and sonicated extracts of Porphyromonas
      gingivalis 2561 on osteogenesis in vitro.
AB  - It is well documented that oral microorganisms play a significant role in the
      initiation and progression of periodontal disease. By using various in vitro
      models, it has been shown that some bacteria considered periodontal pathogens or
      their products can stimulate bone resorption and some other parameters of
      osteoblast-like cell activity. However, the effects of these organisms and their
      products on osteogenesis itself are not known. This study was undertaken to
      determine the direct effects of metabolic products and sonicated extracts of
      Porphyromonas gingivalis on bone formation in the chick periosteal osteogenesis
      model. Cultures of P. gingivalis 2561 were grown under standard anaerobic culture
      conditions. The spent medium was collected, and following centrifugation,
      sonicated bacterial extracts were prepared from the bacterial pellet. These were
      added in various proportions to the chick periosteal osteogenesis cultures.
      Sonicated extracts were further fractionated into five molecular-size ranges and
      similarly tested. Parameters of osteogenesis, including alkaline phosphatase
      activity, calcium and Pi accumulation, and collagen synthesis, were measured on 6
      day-old cultures. Compared with controls devoid of bacterial products,
      osteogenesis was inhibited significantly in cultures treated with either
      conditioned medium or extracts obtained from P. gingivalis. Various amounts of
      inhibitory activity were observed in the different ultrafiltration molecular-size
      fractions, with very profound inhibitory effects observed in the < 5-kDa range.
      Histological observations indicated the presence of cells, some bone, and/or new
      fibrous connective tissue at all concentrations, indicating that toxicity was not
      a factor. These results suggest that periodontal pathogens such as P. gingivalis
      might contribute to the bone loss in periodontal diseases not only by stimulating
      resorption but, possibly, by inhibiting bone formation directly.

PMID- 8132336
TI  - Apoptosis as a mechanism of cytolysis of tumor cells by a pathogenic free-living
      amoeba.
AB  - Previous studies have shown that trophozoites of the pathogenic free-living
      amoeba Acanthamoeba castellanii rapidly lysed a variety of tumor cells in vitro.
      Tumor cells undergoing parasite-mediated lysis displayed characteristic cell
      membrane blebbing reminiscent of apoptosis. The present investigation examined
      the role of apoptosis (programmed cell death) in Acanthamoeba-mediated tumor cell
      lysis. The results showed that more than 70% of tumor cell DNA was fragmented
      following exposure to Acanthamoeba cell extracts. By contrast, only 7% of
      untreated control cells underwent DNA fragmentation. DNA fragmentation increased
      significantly in a dose-dependent fashion following concentration of the parasite
      extract. Apoptosis was also confirmed by DNA ladder formation. Characteristic DNA
      ladders, consisting of multimers of approximately 180 to 200 bp, were produced by
      tumor cells exposed to Acanthamoeba cell extracts. The morphology of tumor cell
      lysis was examined by light and scanning electron microscopy. Tumor cells exposed
      to parasite extract displayed morphological features characteristic of apoptosis
      including cell shrinkage, cell membrane blebbing, formation of apoptotic bodies,
      and nuclear condensation. By contrast, similar effects were not found in tumor
      cells exposed to extract similarly prepared from normal mammalian cells (i.e.,
      human keratocytes). The results suggest that at least one species of pathogenic
      free-living amoeba is able to lyse tumor cells by a process that culminates in
      apoptosis.

PMID- 8132337
TI  - Novel path to apoptosis: small transmembrane pores created by staphylococcal
      alpha-toxin in T lymphocytes evoke internucleosomal DNA degradation.
AB  - Peripheral-blood human T lymphocytes were treated with Staphylococcus aureus
      alpha-toxin. Membrane permeabilization was assessed by measuring efflux of K+ and
      Rb+ and influx of Na+, Ca2+, and propidium iodide. Cellular ATP and [3H]thymidine
      incorporation following lectin stimulation were measured as parameters for cell
      viability. Internucleosomal cleavage characteristic of programmed cell death was
      assessed by agarose gel electrophoresis and by quantifying low-molecular-weight,
      [3H]thymidine-labeled DNA fragments. Nanomolar concentrations of alpha-toxin
      evoked protracted, irreversible ATP depletion in both activated and resting T
      lymphocytes. Toxin-damaged cells also lost their ability to incorporate
      [3H]thymidine upon subsequent stimulation with phytohemagglutinin. These cells
      carried toxin hexamers, and their plasma membranes became permeable for
      monovalent ions but not for Ca2+ and propidium iodide. The permeabilization event
      was followed by internucleosomal DNA degradation characteristic of programmed
      cell death. Membranes of cells treated with high toxin doses (> 300 nM) became
      permeable to both Ca2+ and propidium iodide. In this case, ATP depletion occurred
      within minutes and no DNA degradation was observed. When cells were suspended in
      Na(+)-free buffer, alpha-toxin applied at low doses still bound and formed
      hexamers. However, these cells displayed neither DNA degradation nor loss of
      viability. The data indicate that formation of very small but not of large alpha
      toxin pores may trigger programmed cell death in lymphocytes and that
      uncontrolled flux of Na+ ions may be an important event precipitating the suicide
      cascade.

PMID- 8132338
TI  - Use of in vivo complementation in Mycobacterium tuberculosis to identify a
      genomic fragment associated with virulence.
AB  - Novel molecular tools and genetic methods were developed to isolate genomic
      fragments of Mycobacterium tuberculosis that may be associated with virulence. We
      sought to restore virulence, a characteristic of M. tuberculosis that is
      correlated with growth rate in mouse spleen and lung tissue, to the avirulent
      strain H37Ra by complementation. A representative library of the virulent M.
      tuberculosis strain H37Rv was constructed and transformed into H37Ra. Enrichment
      for individual faster-growing recombinants was achieved by passage of pools of
      H37Ra transformants harboring the H37Rv library through mice. A molecular
      strategy was devised to isolate and clone the H37Rv genomic DNA fragment ivg,
      which conferred a more rapid in vivo growth rate to H37Ra.

PMID- 8132340
TI  - Differences in adhesion of Candida albicans 3153A cells exhibiting switch
      phenotypes to buccal epithelium and stratum corneum.
AB  - Cells of the laboratory strain 3153A of Candida albicans can be stimulated to
      undergo high-frequency phenotypic switching by a low dose of UV. We have compared
      the adhesive properties of cells exhibiting the basic original smooth (o-smooth)
      phenotype and three switch phenotypes (star, irregular wrinkle, and revertant
      smooth) to buccal epithelium and stratum corneum. The generalized hierarchy of
      adhesion is as follows: o-smooth > irregular wrinkle > revertant smooth > star.
      This is the inverse of the hierarchy of the proportions of elongate hyphae formed
      by these phenotypes in culture. These results suggest that the differences in
      adhesion between o-smooth and the three switch phenotypes of strain 3153A
      reflect, at least in part, the level of interference due to the formation of
      elongate hyphae, which tend to cause clumping in suspension. No major differences
      in the levels of adhesion of cells of the different phenotypes between buccal
      epithelium and stratum corneum were observed. Results which demonstrate that
      buccal epithelium induces germination (hypha formation) by conditioning the
      medium are also presented.

PMID- 8132339
TI  - lasA and lasB genes of Pseudomonas aeruginosa: analysis of transcription and gene
      product activity.
AB  - The lasA gene was the first of the Pseudomonas aeruginosa genes involved in
      proteolysis and elastolysis to be cloned and sequenced. Its function and
      significance have been studied by genetic approaches (D. S. Toder, M. J.
      Gambello, and B. H. Iglewski, Mol. Microbiol. 5:2003-2010, 1991) and by attempts
      to purify an active fragment of the protein (J. E. Peters and D. R. Galloway, J.
      Bacteriol. 172:2236-2240, 1990). To further study LasA in vivo, we have
      constructed and characterized an insertional mutant in the lasA gene in strain
      PAO1 (PAO-A1) and in the lasB insertional mutant, PAO-B1. Analysis of these
      isogenic strains demonstrates that the lasA lesion diminished elastolysis more
      than proteolysis and that LasA is required for staphylolytic activity. Despite
      previous suggestions that lasB elastase cleaves the LasA protein, the size of the
      LasA protein was the same whether or not lasB elastase was present. Expression of
      lasA in a lasR-negative mutant, PAO-R1, demonstrated that the LasA protein is
      produced in an active form in the absence of (lasB) elastase or alkaline protease
      and is itself a protease with elastolytic activity. We also observed that PAO-A1
      was closer to the parental phenotype, with respect to elastolytic and proteolytic
      activities, than the previously characterized, chemically induced lasA mutant PAO
      E64. Quantification of promoter activity with lasA::lacZ and lasB::lacZ fusions
      suggests that PAO-E64 harbors a mutation in a gene which regulates expression of
      both lasA and lasB.

PMID- 8132342
TI  - Maternal transmission of immunity to Eimeria maxima: enzyme-linked immunosorbent
      assay analysis of protective antibodies induced by infection.
AB  - Vaccination of broiler chickens against Eimeria infection is problematic because
      of the need to ensure that birds are protected from the time of hatching. We have
      therefore investigated the feasibility of protecting hatchling broilers via
      maternal transfer of protective antibodies from hens to their offspring. Oral
      infection of broiler breeder hens with 20,000 sporulated Eimeria maxima oocysts
      caused production of antibodies which were passed into the egg yolk and
      subsequently to hatchlings. The level of specific antibodies in the yolks to
      unsporulated oocysts, sporulated oocysts, merozoites, and gametocytes was
      assessed by enzyme-linked immunosorbent assays. The levels in yolks of antibodies
      to all developmental stages peaked 3 to 4 weeks after infection of the hens.
      Groups of 10 hatchlings were challenged at 3 days of age by oral infection with
      100 sporulated E. maxima oocysts. In the first experiment, the mean 4-day (days 6
      to 9 post-infection) total number of oocysts excreted in the feces of chicks from
      eggs collected 3 weeks after infection of the hens was (0.6 +/- 0.4) x 10(6)
      (mean +/- standard error) compared with (9.9 +/- 1.4) x 10(6) for the progeny of
      uninfected hens, which represents a greater than 90% reduction. However, oocyst
      excretion by chicks from eggs collected 7 or 8 weeks after infection of the hens
      was only 47 or 68% lower than control values, reflecting declining levels of
      protective antibodies. In a second experiment, in which the hens were somewhat
      older and pretreated by intramuscular injection of saline in the emulsifying
      agent, Arlacel A, the period for which protective antibodies were transferred to
      hatchlings was prolonged. Thus, oocyst excretion by challenged hatchlings from
      eggs collected for an 8-week period after infection of the hens was more than 90%
      lower than oocyst excretion by control chicks, and even hatchlings of eggs
      collected 19 weeks after infection of the hens showed a 60% reduction in oocyst
      output. In both experiments, the levels of immunoglobulin G (IgG) antibodies to
      all developmental stages in yolks or hatchling sera were very strongly correlated
      with maternally derived immunity to E. maxima. In contrast, parasite-specific IgM
      or IgA was not detectable, either in egg yolk or egg white. These results
      demonstrate the ability of IgG antibodies to protect against E. maxima in
      poultry, thus raising the possibility of using protective maternally derived IgG
      antibodies to identify potentially protective parasite antigens and indicating
      the feasibility of using maternal immunization as a means for parasite control.

PMID- 8132341
TI  - Analysis of genes encoding two unique type IIa immunoglobulin G-binding proteins
      expressed by a single group A streptococcal isolate.
AB  - An emm-like gene (emmL) and a fcrA gene from group A streptococcal strain 64/14
      (emmL64/14 and fcrA64/14) were amplified by PCR and force cloned into the heat
      inducible expression vector pJLA 602. The emmL gene encoded a recombinant protein
      that bound human IgG1, IgG2, and IgG4 in a nonimmune fashion. This is the
      reactivity profile of a type IIa IgG-binding protein. The emmL64/14 gene product
      was antigenically similar to the previously identified high-molecular-weight type
      IIa IgG-binding protein of strain 64/14 and had an N-terminal sequence identical
      to that of the wild-type protein. The fcrA gene also encoded a recombinant
      protein with type IIa functional activity. This protein was similar to the lower
      molecular-weight type IIa IgG-binding protein previously isolated from strain
      64/14 and was antigenically distinct from the higher-molecular-weight type IIa
      protein encoded by the emmL64/14 gene. The sequences for both genes including the
      intervening regions are presented. The emmL gene demonstrates significant
      homology to other class I emm and emmL genes expressed by opacity factor-negative
      group A streptococcal isolates. The fcrA gene was found to be homologous to other
      fcrA genes normally present in opacity factor-positive group A isolates. The
      sequence upstream of the fcrA gene and the intervening sequence between the end
      of the fcrA gene and the start of the emmL gene were similar to those reported
      for other fcrA genes.

PMID- 8132343
TI  - Nucleotide sequence of a Porphyromonas gingivalis gene encoding a surface
      associated glutamate dehydrogenase and construction of a glutamate dehydrogenase
      deficient isogenic mutant.
AB  - The nucleotide sequence for a surface-associated protein (A. Joe, A. Yamamoto,
      and B. C. McBride, Infect. Immun. 61:3294-3303, 1993) of Porphyromonas gingivalis
      was determined. The structural gene comprises 1,338 bp and codes for a protein of
      445 amino acids. The deduced molecular weight of the protein is 49,243. A data
      base search for homologous proteins revealed significant sequence similarity to
      the subunit protein of glutamate dehydrogenases (GDHs) isolated from various
      sources. This protein, which was previously labelled PgAg1, will now be called
      GDH. Recombinant GDH was purified to homogeneity, and native GDH was partially
      purified from P. gingivalis. Both preparations exhibited NAD-dependent GDH
      activity. Intact P. gingivalis and an extract of cell surface components also
      demonstrated NAD-dependent GDH activity. To help elucidate the role of this
      protein, an isogenic mutant of P. gingivalis lacking the GDH protein was
      generated by deletion disruption. Biological characterization of the mutant
      strain, P. gingivalis E51, demonstrated complete loss of GDH activity. Immunogold
      bead labelling of intact cells showed that GDH was no longer present on the
      surface of the bacterial cell. The GDH-negative mutant displayed impaired cell
      growth, as demonstrated by an increased generation time and an inability to grow
      to the same cell density as the parent.

PMID- 8132344
TI  - Isolation and characterization of a gene involved in hemagglutination by an avian
      pathogenic Escherichia coli strain.
AB  - In this article, we report the isolation and characterization of a gene that may
      be important in the adherence of avian pathogenic Escherichia coli to the avian
      respiratory tract. The E. coli strain HB101, which is unable to agglutinate
      chicken erythrocytes, was transduced with cosmid libraries from the avian
      pathogenic E. coli strain chi 7122. Enrichment of transductants that could
      agglutinate chicken erythrocytes yielded 19 colonies. These isolates contained
      cosmids that encompassed four nonoverlapping regions of the E. coli chromosome.
      Only one group of cosmids, represented by pYA3104, would cause E. coli CC118 to
      agglutinate chicken erythrocytes. A 10-kb fragment of this cosmid was subcloned
      in pACYC184. Transposon mutagenesis of this fragment with Tn5seq1 indicated that
      a contiguous 4.4-kb region of cloned DNA was required for hemagglutination. In
      vitro transcription/translation assays indicated that this 4.4-kb region of DNA
      encoded one protein of approximately 140 kDa. The nucleotide sequence of this
      region was determined and found to encode one open reading frame of 4,134
      nucleotides that would encode a protein of 1,377 amino acids with a deduced
      molecular weight of 148,226. This gene confers on E. coli K-12 a temperature
      sensitive hemagglutination phenotype that is best expressed when cells are grown
      at 26 degrees C, and we have designated this gene tsh and the deduced gene
      product Tsh. Insertional mutagenesis of the chromosomal tsh gene in chi 7122 had
      no effect on hemagglutination titers. The deduced protein was found to contain
      significant homology to the Haemophilus influenzae and Neisseria gonorrhoeae
      immunoglobulin A1 proteases. These data indicate that (i) a single gene isolated
      from the avian pathogenic E. coli strain chi 7122 will confer on E. coli K-12 a
      hemagglutination-positive phenotype, (ii) chi 7122 contains at least two distinct
      mechanisms to allow hemagglutination to occur, and (iii) the hemagglutinin Tsh
      has homology with a class of proteins previously not known to exist in E. coli.

PMID- 8132346
TI  - Immunobiological activities of Helicobacter pylori porins.
AB  - Studies were carried out on some biological activities of Helicobacter pylori
      porins in vitro. We extracted and purified a porin with an apparent molecular
      mass of 30 kDa. Human polymorphonuclear leukocytes preincubated with H. pylori
      porins showed a decrease of chemotaxis, of adherence to nylon wool, and of
      chemiluminescence. Used as chemotaxins in place of zymosan-activated serum or as
      chemotaxinogens in place of zymosan, the porins induced polymorphonuclear
      leukocyte migration. Human monocytes and lymphocytes cultivated in the presence
      of H. pylori porins released cytokines. Release of the various cytokines studied
      was obtained with differentiated kinetics and at various porin concentrations.
      Starting only 3 h after culture, tumor necrosis factor alpha is released quickly,
      reaching a peak at 18 h, at a porin concentration of 1 microgram/ml/10(6) cells.
      Interleukin-6 (IL-6) appears later, with a peak at 10 micrograms/ml/10(6) cells,
      while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin
      concentration of 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h
      of culture, with a peak at 24 h, at a porin concentration of 10
      micrograms/ml/10(6) cells. Lymphocytes stimulated by H. pylori porins release
      gamma interferon after 18 h of culture at higher concentrations of porins (20
      micrograms/ml/10(6) cells). Granulocyte macrophage colony-stimulating factor is
      released from 6 to 48 h at a concentration of 1 microgram/ml/10(6) cells, while
      both IL-3 and IL-4 are released after 18 h of culture at different porin
      concentrations (0.1 and 1 microgram/ml/10(6) cells, respectively). Our results
      lead us to think that during H. pylori infection, surface components, porins in
      particular, are able to induce a series of chain reactions ranging from the
      inflammatory to the immunological responses.

PMID- 8132345
TI  - Similarity between the 38-kilodalton lipoprotein of Treponema pallidum and the
      glucose/galactose-binding (MglB) protein of Escherichia coli.
AB  - The recent discovery that abundant and immunogenic lipoproteins constitute the
      integral membrane proteins of Treponema pallidum has prompted efforts to
      investigate their importance in the physiology and ultrastructure of the organism
      and in immune responses during infection. Earlier studies identified a 38-kDa
      lipoprotein of T. pallidum believed to be specific to the pathogen. In the
      present study, monoclonal antibodies generated against the 38-kDa lipoprotein of
      T. pallidum reacted with cognate 37-kDa molecules in the nonpathogens Treponema
      phagedenis, Treponema denticola, and Treponema refringens. Cloning and expression
      of the 38-kDa-lipoprotein gene of T. pallidum in Escherichia coli revealed that
      the recombinant product displayed a slightly larger (39-kDa) apparent molecular
      mass but remained reactive with anti-38-kDa-protein monoclonal antibodies. The
      recombinant product was processed and acylated in E. coli. DNA and amino acid
      sequence analyses indicated an open reading frame encoding 403 amino acids, with
      the first 25 amino acids corresponding to a leader peptide terminated by a signal
      peptidase II processing site of Val-Val-Gly-Cys. The predicted mature protein is
      378 amino acids in length with a deduced molecular weight of 40,422 (excluding
      acylation). Southern blotting failed to demonstrate in nonpathogenic treponemes
      genomic sequences homologous with the 38-kDa-lipoprotein gene of T. pallidum.
      Computer analysis revealed that the 38-kDa lipoprotein of T. pallidum had 34.2%
      identity and 58.9% similarity with the glucose/galactose-binding protein (MglB)
      of E. coli and Salmonella typhimurium. Furthermore, of the 19 amino acids of MglB
      involved in carbohydrate binding, the 38-kDa lipoprotein had identity with 11.
      These studies have allowed the first putative functional assignment (carbohydrate
      binding) to a T. pallidum integral membrane protein. Recognition of this
      potential physiological role for the 38-kDa lipoprotein underscores the
      possibility that the membrane biology of T. pallidum may more closely resemble
      that of gram-positive organisms, which also utilize lipoproteins as anchored
      transporters, than that of gram-negative bacteria to which T. pallidum often is
      analogized.

PMID- 8132347
TI  - Tumor necrosis factor alpha (TNF-alpha) and TNF-beta and their receptors in
      experimental cutaneous leishmaniasis.
AB  - Experimental infection of BALB/c mice with Leishmania major leads to lesions
      which progress without healing and visceralization, reproducing the most severe
      forms of human leishmaniasis, while resistant mice like CBA spontaneously resolve
      lesions and develop protective immunity. Given the conflicting data pertaining to
      the role of tumor necrosis factor alpha (TNF) in Leishmania infection, we
      analyzed the expression of TNF, tumor necrosis factor beta (lymphotoxin), and TNF
      receptor type I (TNF-RI) and type II (TNF-RII) genes in vivo and correlated TNF
      gene expression in vivo with the production of biologically active TNF by
      lymphoid cells in vitro. No significant difference in the expression of TNF mRNA
      was found between susceptible and resistant strains of mice during the course of
      infection. The depletion of CD4+ T cells in vitro did not change the level of TNF
      mRNA in BALB/c lymph node cells but led to the total disappearance of TNF mRNA in
      CBA mice. Unprimed spleen cells did not produce detectable amounts of TNF,
      whereas 1 week after infection, TNF bioactivity was detected and increased in
      both strains of mice until 5 weeks of infection. While neutralization of TNF
      activity in vivo did not alter the course of infection in BALB/c mice, in CBA
      mice it led to an increase in lesion size and a delay in the healing process but
      did not interfere significantly with the outcome of infection. Finally, no
      significant difference in the levels of lymphotoxin, TNF-RI, or TNF RII mRNA
      expression was found between both strains. The information resulting from these
      investigations supports the notion that, in vivo, TNF is not the decisive factor
      responsible for the resistant versus susceptible phenotype in leishmania
      infection.

PMID- 8132348
TI  - Characterization of a rabbit cationic protein (CAP18) with lipopolysaccharide
      inhibitory activity.
AB  - Cationic antibacterial proteins (CAP) were purified from rabbit granulocytes, and
      the effects of CAP on lipopolysaccharide (LPS)-induced tissue factor generation
      by murine peritoneal macrophages and human blood monocytes were studied. CAP were
      purified from rabbit peritoneal leukocytes by using as an assay the agglutination
      of erythrocytes coated with Re-LPS. Two proteins with CAP activity, CAP18 (18
      kDa) and CAP7 (7 kDa), were isolated by acid extraction, ethanol precipitation,
      affinity chromatography, gel filtration, and reverse-phase high-pressure liquid
      chromatography. On the basis of protein sequencing, CAP7 was identified as the C
      terminal fragment of CAP18, designated CAP18(106-142). Various forms of LPS (S
      LPS, Re-LPS, and lipid A) activate murine macrophages and human blood monocytes
      to generate tissue factor (tissue thromboplastin). Incubation of LPS for 18 h
      with partially purified CAP (heparin-Sepharose fraction) inhibited the capacity
      of LPS to induce tissue factor; however, purified CAP18 inhibited about 75% of
      the activity of S-LPS after 1 h of incubation. CAP more effectively inhibited S
      LPS than Re-LPS or lipid A. Synthetic CAP18(106-142) inhibited LPS-induced tissue
      factor generation by murine macrophages. CAP18(106-142) has greater LPS-binding
      and LPS-neutralizing activities than CAP18. We hypothesize that CAP18 and the
      derivative peptide, CAP18(106-142), bind to LPS and alter the capacity of LPS to
      initiate disseminated intravascular coagulation. In this regard, CAP may have
      therapeutic potential for sepsis and endotoxin shock.

PMID- 8132349
TI  - Mucosal and systemic immunizations with killed Pseudomonas aeruginosa protect
      against acute respiratory infection in rats.
AB  - The aim of this study was to determine the efficacies of prior mucosal (oral,
      intra-Peyer's patch, or intratracheal) and systemic (subcutaneous) immunizations
      with killed Pseudomonas aeruginosa in clearance of an acute P. aeruginosa
      respiratory infection in rats. Rats were immunized with paraformaldehyde-killed
      P. aeruginosa at various doses, and 2 weeks later, the rats were challenged with
      a log10 dose of 8.7 live bacteria. This dose was fatal for unimmunized rats, with
      death occurring approximately 12 h after challenge. The numbers of surviving
      bacteria in the airways and lung tissue were determined by analyses of
      bronchoalveolar lavage fluid (BAL) and lung homogenate samples, respectively.
      Enhanced bacterial clearance was associated with survival of intra-Peyer's patch
      immunized rats. Determination of bacterial clearance in BAL 4 h after challenge
      demonstrated that the use of all immunization routes led to significant clearance
      compared with the bacterial levels in unimmunized controls (the order of
      effectiveness was intra-Peyer's patch > oral-intratracheal > intratracheal >
      subcutaneous > oral). Bacterial clearance in the lung homogenate was also
      significantly greater for all immunization routes than in the unimmunized
      controls (the order of effectiveness was intra-Peyer's patch > subcutaneous >
      oral-intratracheal > oral = intratracheal). Prior oral immunization with killed
      P. aeruginosa also induced enhanced bacterial clearance of heterologous strains
      of P. aeruginosa, Haemophilus influenzae, and to a lesser extent, Klebsiella
      pneumoniae. Because of the ease of antigen delivery, oral immunization with
      killed P. aeruginosa may be an important route of immunization for induction of
      enhanced bacterial clearance of subsequent acute respiratory infection with P.
      aeruginosa and other gram-negative bacteria.

PMID- 8132350
TI  - Humoral immune response to class 1 outer membrane protein during the course of
      meningococcal disease.
AB  - We have determined the amounts of specific anti-class 1 outer membrane protein
      antibodies in sera from 25 patients during the course of systemic meningococcal
      disease, using purified class 1 protein as the sensitizing antigen in an enzyme
      linked immunosorbent assay. The class 1 protein was obtained from a variant of
      strain 44/76 (B:15:P1.7,16) lacking class 3 and class 4 outer membrane proteins.
      Specific anti-class 1 (serosubtype P1.7,16) outer membrane protein immunoglobulin
      G (IgG) antibody levels increased significantly in 12 patients (12 of 25; 48%),
      regardless of the serotype of the infecting strain, indicating that the
      antibodies reacted in part with epitopes not determined by the monoclonal
      antibodies used for serotyping. Most patients had low levels of anti-class 1 IgG
      antibodies during the acute illness. The antibody levels peaked during the second
      week of disease and returned to near baseline levels in sera collected 6 weeks to
      12 months after the onset of the disease. The majority of the specific anti-class
      1 IgG antibodies bound to surface-exposed epitopes on whole bacteria and belonged
      to the IgG1 and IgG3 subclasses. Anti-class 1 IgA and IgM antibodies were not
      detected in any of the patient sera. Prior to disease, seven patients had been
      immunized with a meningococcal outer membrane vesicle vaccine developed from
      strain 44/76 (P1.7,16). None of these patients was infected with meningococcal
      strains containing class 1 protein homologous or partly homologous to that of the
      vaccine strain, indicating serosubtype-specific protection. The highest anti
      class 1 IgG antibody peak levels were seen in immunized patients infected with
      strains of heterologous serotype, suggesting an anamnestic response. However,
      these patients were not protected from meningococcal disease after immunization.

PMID- 8132351
TI  - Cytokine gene expression by cultures of human lymphocytes with autologous
      Mycobacterium tuberculosis-infected monocytes.
AB  - In order to better understand the immunoregulation following Mycobacterium
      tuberculosis infection, cytokine mRNA induction in response to in vitro infection
      of human monocytes with live virulent M. tuberculosis H37Rv cocultured with
      autologous lymphocytes was quantitated by reverse transcriptase-PCR. Induced
      levels of interleukin 1 beta (IL-1 beta), IL-2, tumor necrosis factor alpha, and
      gamma interferon (IFN-gamma) were compared among groups of individuals
      representing three phases of immunity to infection with M. tuberculosis: naive
      normal control subjects, purified protein derivative (PPD)-reactive normal
      donors, and individuals with active tuberculosis (TB [diseased]). Levels of IL-1
      beta and tumor necrosis factor alpha mRNA in cocultured cells from TB patients
      were 51 and 45%, respectively, of those obtained in cells from sensitized healthy
      volunteers and were comparable to those from naive normal donors.
      Lymphoproliferative responses to M. tuberculosis and induction of the T-cell
      cytokine IL-2 were predictably high in the cells of PPD-sensitized donors, low in
      normal naive individuals, and variable among TB patients. In contrast, the
      induced level of another lymphokine, IFN-gamma, did not follow the pattern seen
      in IL-2 induction. Infection with live M. tuberculosis induced high levels of IFN
      gamma mRNA in lymphocytes of both PPD-sensitized and normal naive donors compared
      with those of TB patients. Interestingly, polyclonal stimulation with the mitogen
      concanavalin A induced similar IFN-gamma levels in cells from all three donor
      groups. The high level of IFN-gamma induced by the infection of monocytes from
      naive normal donors suggests a role for natural killer (NK) cells in the
      production of IFN-gamma in this coculture system. This response appears
      independent of the role performed by T cells.

PMID- 8132352
TI  - Molecular cloning, sequence analysis, and expression of the gene encoding the
      immunodominant 32-kilodalton protein of Cowdria ruminantium.
AB  - Cowdria ruminatium, the causative agent of heartwater disease, expresses an
      immunodominant and conserved 32-kilodalton protein (MAP1; formerly called Cr32),
      which is currently in use for serodiagnosis of the disease. The gene encoding
      this protein, designated map1, was detected, cloned, and characterized. The gene
      is conserved between four different stocks of C. ruminantium originating from
      Senegal, Sudan, South Africa, and Zimbabwe. Homology searches revealed MAP1 to be
      homologous to the Anaplasma marginale surface protein MSP4, a potential
      protective antigen. The MAP1 protein, expressed in Escherichia coli fused with
      glutathione S-transferase, is specifically recognized by sera from animals
      infected with seven different stocks of C. ruminantium.

PMID- 8132353
TI  - Analysis of hydrolytic products from choline-labeled host cell phospholipids
      during growth of Rickettsia prowazekii.
AB  - A phospholipase activity has been associated with the interaction of Rickettsia
      prowazekii with the surface of erythrocytes and competent host cells as well as
      during the growth of the rickettsiae within their host cells. Both fatty acid and
      lysophosphatides have been found in the interaction of rickettsiae with the
      surface of eucaryotic cells; this finding provided strong evidence for the
      activity of a phospholipase A. However, fatty acids, but not lysophosphatides,
      were found during the growth of rickettsiae within cells in which the
      phospholipids had been radiolabeled with oleic acid; this observation left the
      type of phospholipase activity in doubt. In this study, the water-soluble
      components of phospholipid hydrolysis by phospholipase A plus lysophospholipase
      and phospholipase C were determined following the growth of rickettsiae in host
      cells in which the phospholipids had been radiolabeled with choline. In infected
      cells relative to mock-infected cells, there was a loss of phosphatidylcholine
      with a corresponding increase not in lysophosphatidylcholine but in the water
      soluble components. There was a large increase in glycerylphosphorylcholine
      (185%) and a smaller increase in phosphorylcholine (16%). These results indicate
      that both phospholipase A activity (plus a lysophospholipase activity) and
      phospholipase C were increased during infection by R. prowazekii and that the
      former was the predominant activity.

PMID- 8132354
TI  - Binding of Paracoccidioides brasiliensis to laminin through surface glycoprotein
      gp43 leads to enhancement of fungal pathogenesis.
AB  - Extracellular matrix protein laminin binds specifically to yeast forms of
      Paracoccidioides brasiliensis and enhances adhesion of the fungus to the surface
      of epithelial Madin-Darby canine kidney cells in vitro. Immunoblotting of fungal
      extracts showed that the gp43 glycoprotein is responsible for adhesion. This was
      confirmed by binding assays using purified gp43, with a Kd of 3.7 nM. The coating
      of P. brasiliensis yeast forms with laminin before injection into hamster
      testicles enhanced the fungus virulence, resulting in a faster and more severe
      granulomatous disease. These results indicate that interaction of fungi with
      extracellular matrix elements may constitute a basis for the evolution of fungal
      infection toward regional spreading and dissemination.

PMID- 8132355
TI  - Anti-lipoteichoic acid antibodies enhance release of cytokines by monocytes
      sensitized with lipoteichoic acid.
AB  - Lipoteichoic acid (LTA) from gram-positive bacteria can stimulate monocytes to
      produce cytokines. To ascertain whether aggregation of LTA receptors can
      contribute to this effect, human monocytes were sensitized with LTA from
      Streptococcus pyogenes, washed, and treated with anti-LTA antibodies. The
      addition of anti-LTA antibodies or F(ab')2 fragments markedly enhanced the
      aggregation of LTA receptors, as evidenced by indirect immunofluorescence and the
      release of tumor necrosis factor alpha and interleukin-1 beta. These findings
      suggest that aggregation of LTA receptors of monocytes is required for triggering
      marked cytokine responses.

PMID- 8132356
TI  - Potential for reacquisition of cholera enterotoxin genes by attenuated Vibrio
      cholerae vaccine strain CVD 103-HgR.
AB  - The potential for reacquisition of ctxA genes by attenuated Vibrio cholerae O1
      vaccine strain CVD 103-HgR was examined by performing a series of mating
      experiments under a variety of in vivo and in vitro conditions. We found no
      evidence that CVD 103-HgR could reacquire ctxA genes from wild-type V. cholerae
      O1 strains. However, if the donor V. cholerae O1 strains were genetically
      manipulated to add genes that allow chromosomal gene transfer, then ctxA
      sequences could be acquired by CVD 103-HgR. The minimal excretion of CVD 103-HgR
      by vaccinees and the refractoriness to reacquisition of ctxA sequences suggest
      that this well-tolerated, highly immunogenic live oral cholera vaccine will have
      a minimal environmental impact.

PMID- 8132357
TI  - Trypanosoma cruzi-induced immunosuppression: blockade of costimulatory T-cell
      responses in infected hosts due to defective T-cell receptor-CD3 functioning.
AB  - A model of experimental Trypanosoma cruzi murine infection with chemically
      induced metacyclic forms (opossum clone Dm28c) showed a marked state of T-cell
      unresponsiveness during acute phase, but lacked evidence of suppressor cell
      activity. Spleen cells from infected mice were suppressed in vitro in responses
      to T-cell activators concanavalin A, anti-Thy1 monoclonal antibody (MAb), and
      anti-CD3 MAb compared with spleen cells from control littermates. Activation with
      accessory cell-independent stimulus provided by immobilized anti-CD3 was
      defective in splenic CD4-positive T cells from infected mice, but not in such
      cells from control mice. No evidence of splenic suppressor cell activity was
      found in cell-mixing experiments using nylon-passed T cells from control and
      infected donors. Kinetic experiments showed that there was a discrete stage in
      infection when T cells were already suppressed in response to anti-CD3 but still
      responded to anti-CD69 MAb. In these T cells, immobilized anti-CD3 failed to
      enhance simultaneous CD69 responses, although anti-CD3 enhanced CD69 responses in
      control T cells from uninfected donors. These results demonstrate an intrinsic
      defect in T-cell receptor-mediated T-cell activation, which could be a mechanism
      generating T-cell suppression during infection by T. cruzi.

PMID- 8132358
TI  - Phagocytosis of medically important yeasts by polymorphonuclear leukocytes.
AB  - Phagocytosis is a critical function of polymorphonuclear leukocytes in the
      control of mycotic infections. By using a modified fluorescence quenching assay
      to distinguish between attached and ingested organisms, we determined the percent
      phagocytosis of several medically important yeasts. The percentages of
      phagocytosis of serum-opsonized Candida albicans, Candida tropicalis, Candida
      parapsilosis, and Torulopsis glabrata were all comparable at 37 degrees C. By
      comparison, there was significantly less phagocytosis of Cryptococcus neoformans
      and Trichosporon beigelii isolates (P < 0.001). Thus, phagocytosis of C. albicans
      by polymorphonuclear leukocytes is comparable to that of species other than C.
      albicans but is significantly greater than that of the basidiomycetous yeasts T.
      beigelii and C. neoformans.

PMID- 8132359
TI  - Inhibitory effect of deferoxamine or macrophage activation on transformation of
      Paracoccidioides brasiliensis conidia ingested by macrophages: reversal by
      holotransferrin.
AB  - Conidia of P. brasiliensis ingested by murine macrophages at 37 degrees C showed
      enhanced transformation to yeast cells and further intracellular growth compared
      with conidia in culture medium alone. Treatment of macrophages with the iron
      chelator deferoxamine inhibited the intracellular conidium-to-yeast
      transformation. Cytokine-activated macrophages could also exert this inhibitory
      effect. Holotransferrin reversed the inhibitory effect of either deferoxamine or
      activated macrophages on intracellular conidium-to-yeast transformation. These
      results indicate that iron restriction is one of the mechanisms by which
      activated macrophages control the intracellular transformation of ingested
      conidia and growth of yeast cells.

PMID- 8132360
TI  - Adherence of Candida albicans to endothelial cells is inhibited by prostaglandin
      I2.
AB  - The adherence of Candida species yeast cells to bovine and human endothelium was
      measured. The adherence phenomenon is a saturable event which can be altered by
      the release of prostaglandin I2 (PGI2 or prostacyclin) by endothelial cells.
      Release of PGI2 by endothelium has a protective effect, reducing Candida albicans
      yeast cell adherence to endothelial cells in a dose-dependent manner. Conversely,
      C. albicans appears to inhibit the release of PGI2 by endothelial cells and thus
      perhaps is capable of increasing the number of yeast cells which adhere to
      endothelium. Furthermore, a long-acting analog of PGI2, carbacyclin, reduced the
      number of yeast cells adhering to human platelet aggregates. Thus, it is possible
      that the release of PGI2 by endothelium has a protective effect against the
      hematogenous dissemination of C. albicans and its ability to adhere to vascular
      endothelium and fibrin-platelet matrices.

PMID- 8132361
TI  - Pneumolysin stimulates production of tumor necrosis factor alpha and interleukin
      1 beta by human mononuclear phagocytes.
AB  - Human peripheral blood monocytes and a human monocyte cell line were exposed to
      the toxin pneumolysin. Pneumolysin-exposed cells produced significantly larger
      amounts of tumor necrosis factor alpha and interleukin-1 beta than cells not
      exposed to the toxin. The viability of cells was not affected by the
      concentrations of pneumolysin used in the experiments.

PMID- 8132362
TI  - Factors in human milk that protect against diarrheal disease.

PMID- 8132363
TI  - Bacteraemia due to different groups of beta-haemolytic streptococci: a two-year
      survey and presentation of a case of recurring infection due to Streptococcus
      "equisimilis".
AB  - We present a 2-year survey of bacteraemic episodes due to beta-haemolytic
      streptococci and a case of recurring infection due to group C streptococcus,
      Streptococcus "equisimilis". We found 53 episodes of bacteraemia with beta
      haemolytic streptococci. Group A was the most common, followed by groups B, G and
      C. The proportion of nosocomial cases was the same in all four groups i.e. 24%
      (neonatal cases excluded). The clinical picture presented by groups C and G
      streptococcal cases was indistinguishable from that caused by group A
      streptococci, but patients with group G bacteraemia were older than patients with
      group A bacteraemia. Obvious clinical foci were more common in group A than group
      G cases. Disregarding neonatal cases, most patients had predisposing conditions.
      There was no difference in foci of bacteraemia, predisposing factors, treatment
      and outcome of disease. The overall mortality was 25%.

PMID- 8132364
TI  - Short term treatment of visceral leishmaniasis of the Old World with low dose
      interferon gamma and pentavalent antimony.
AB  - Eight adult patients with visceral leishmaniasis acquired in mediterranean
      countries were treated in a prospective study with a combined immunomodulating
      and antiparasitic regimen consisting of low-dose interferon-gamma (IFN-gamma) and
      pentavalent antimony. The clinical outcome, hematological and parasitological
      parameters, the duration of treatment and number of treatment cycles as well as
      the cumulative dose of pentavalent antimony applied, have been evaluated. The
      combined treatment led to complete resolution of symptoms and parasitological
      cure in all cases of visceral leishmaniasis without major side effects. Combined
      treatment resulted in a significant reduction of duration of treatment (19 vs. 31
      days, p < 0.02) and cumulative dose of pentavalent antimony (11.67 vs. 19.30 g, p
      < 0.02) compared to historical controls (n = 6). No relapses occurred after a
      median follow-up of 9 months (range: 2-28 months). We conclude that combination
      therapy is tolerated well and is highly effective in patients with visceral
      leishmaniasis. The addition of IFN-gamma to standard therapy with pentavalent
      antimony may reduce the cumulative dose of antimonial drugs, shortens the
      treatment period and probably reduces the number of relapses.

PMID- 8132365
TI  - Azithromycin versus penicillin V for the treatment of early Lyme borreliosis.
AB  - In a randomized multicenter therapeutic trial, 32 patients with erythema migrans
      received oral azithromycin 500 mg once daily and 33 patients received
      phenoxymethylpenicillin (penicillin V) 1 million U three times daily for 10 days.
      Follow-up was for a median of 17 (range 3-32) months. Four weeks after initiation
      of therapy, 20 (62%) patients given azithromycin and 17 (51%) patients given
      penicillin V were completely free of all signs and symptoms and did not develop
      new ones subsequently (no significant difference). Three months after initiation
      of therapy, the corresponding figures were 25 (78%) azithromycin and 28 (85%)
      penicillin V recipients (no significant difference). There were only minor
      sequelae such as arthralgia, headache, fatigue, stiff neck and dysesthesia.
      Azithromycin led to a significantly faster resolution of the erythema migrans
      than penicillin V (p < 0.001). Significantly more patients with more severe
      compared with mild initial disease had an elevated IgM antibody titer prior to
      therapy (p < 0.001). Usually mild to moderate side effects occurred in 12
      patients given azithromycin and five patients given penicillin V (p < 0.05).
      Azithromycin appears to be as effective as penicillin V for the treatment of
      early Lyme borreliosis and it seems to clear the erythema migrans more promptly.

PMID- 8132366
TI  - Effect of ceftibuten on the normal intestinal microflora.
AB  - 14 healthy volunteers were given 400 mg ceftibuten orally once daily for ten
      days. Stool specimens were collected before, during and after ceftibuten
      administration. Ceftibuten was well absorbed; on average 123 mg was excreted in
      urine 0-6 h after dosing, while only two volunteers had detectable concentrations
      of ceftibuten in faeces (< or = 3.2 mg/kg). There was an overgrowth of
      enterococci during the administration period, while the numbers of Escherichia
      coli and anaerobic cocci were reduced. Six volunteers were colonized by
      Clostridium difficile during days 4 to 17. Beta-lactamase activity was detected
      in faecal samples from eight volunteers and increased significantly during the
      administration period.

PMID- 8132367
TI  - Comparative study of the efficacy of fluconazole versus amphotericin
      B/flucytosine in surgical patients with systemic mycoses.
AB  - In an open, prospective, randomized study, the efficacy of fluconazole was
      compared with that of the combination amphotericin B/flucytosine. Forty surgical
      patients with deep-seated mycoses were included in the study. Absolute inclusion
      criteria were histological finding of fungi in a tissue sample taken during
      surgery from e.g. peritoneum, pancreas, lungs or trachea, a positive blood
      culture or candida lesion of the eye. According to the random list 20 patients
      received up to 0.5 mg amphotericin B per kg body weight in combination with 3 x
      2.5 g flucytosine (5-FC) daily and 20 patients received fluconazole, 400 mg on
      the first day and then 300 mg daily. The two therapy groups were comparable in
      terms of age, sex and underlying diseases. Gastrointestinal perforations (27
      times) were the most frequent underlying diseases. Candida albicans was the
      fungus most frequently detected microbiologically (34 times). The pathogens were
      eliminated from 12 patients in the fluconazole group and 14 patients in the
      combination group. The median elimination time was 8.5 days in the fluconazole
      group and 5.5 days in the amphotericin B/5-FC group. Six patients died in the
      fluconazole group, whereas five patients died in the comparison group. Side
      effects which necessitated switching of therapy occurred twice in the combination
      group. In deep-seated candida mycoses, surgical patients receiving the
      combination therapy with amphotericin B/5-FC showed an earlier elimination than
      patients on monotherapy with fluconazole. With respect to cure rates there was no
      difference between these two regimens.

PMID- 8132368
TI  - Chlamydial serology in genital infections: ImmunoComb versus Ipazyme.
AB  - The ImmunoComb Chlamydia trachomatis IgG/IgA (Orgenics, Israel) is a new
      serologic test using C. trachomatis L2 elementary bodies (Washington Research
      Foundation, Seattle) as antigen. The Ipazyme IgG/IgA test (Savyon, Israel)
      employs whole cells with C. trachomatis L2 inclusions, i.e. elementary and
      reticulate bodies. Theoretically, the ImmunoComb is expected to be less cross
      reactive (LPS) with Chlamydia pneumoniae than the Ipazyme (LPS and reticulate
      body group specific antigens). Compared with the Ipazyme, the ImmunoComb IgA
      showed both a higher positive predictive value (36% versus 25%) and sensitivity
      (67% versus 33%) for antigen detection in a control group of 100 post partum
      women with a 6% prevalence of C. trachomatis positive cervical smears. In
      sterility patients (45 cases with occluded and 53 with open fallopian tubes) the
      tube status was predicted by the ImmunoComb (Ipazyme) with 74% (72%) positive
      predictive value, 87% (80%) sensitivity, and 87% (81%) negative predictive value.
      IgG/IgA prevalence in 118 patients with C. trachomatis positive cervical smears
      was 85%/55% for the ImmunoComb and 84%/49% for the Ipazyme. The ImmunoComb is
      considerably faster and easier in handling and less subjective in reading than
      the Ipazyme.

PMID- 8132369
TI  - Antibiotic prophylaxis in recurrent erysipelas.
AB  - Recurrences of erysipelas are especially prevalent in patients suffering from
      local impairment of circulation and intervention might thus be of benefit.
      Therefore a prospective, randomized, open study was undertaken to evaluate
      whether daily antibiotic prophylaxis would reduce the risk of recurrence.
      Patients with venous insufficiency or lymphatic congestion who had suffered two
      or more episodes of erysipelas during the previous 3 years and were admitted to
      the Infectious Disease Department at Roslagstull Hospital, Stockholm, Sweden,
      between November 1988 and November 1991 were included. Fourty patients, 20 on
      prophylaxis and 20 controls were followed according to a life table analysis
      during a median time of 15 months. Phenoxymethylpenicillin was prescribed as
      daily prophylaxis (while erythromycin was given to patients allergic to
      penicillin). Recurrences of erysipelas appeared to be reduced by daily antibiotic
      prophylaxis but the effect was not dramatic (p = 0.06). Only in patients with a
      high recurrence rate continuous antibiotic prophylaxis against erysipelas is
      indicated.

PMID- 8132370
TI  - Acinetobacter septicemia: a threat to neonates? Special aspects in a neonatal
      intensive care unit.
AB  - Acinetobacter is one of the organisms responsible for nosocomial infections in
      intensive care, neurosurgery, burn and hemodialysis units. There are only a few
      reports on Acinetobacter infections in neonatal intensive care units. Over a 31
      month period, nine cases of Acinetobacter sepsis occurred in our unit, with four
      deaths. There was a cluster of four cases within 3 days. In this study the
      English literature on this pathogen is reviewed and it is suggested that
      Acinetobacter should be added to the list of organisms causing severe nosocomial
      infection in neonatal intensive care units.

PMID- 8132371
TI  - Group B streptococcal vertebral osteomyelitis in an adult.
AB  - Group B beta-hemolytic streptococcus (Streptococcus agalactiae) vertebral
      osteomyelitis was diagnosed in a 65-year-old man. The patient received a 3-week
      course of in-hospital intravenous ampicillin followed by ceftriaxone and
      continued to receive ceftriaxone therapy on an ambulatory basis for 3 more weeks.
      Hospitalization and follow-up were uncomplicated with no neurological sequelae.
      Review of the medical literature documented only 15 cases of group B
      streptococcal osteomyelitis in adults and only three cases of vertebral
      osteomyelitis due to this pathogen. As in most adult patients with group B
      streptococcal infections, the patient had coexisting chronic conditions (chronic
      obstructive lung disease, diabetes mellitus) but bacteremia was not present.
      Although uncommon, group B streptococcus should be considered as an opportunistic
      pathogen in patients with debilitating conditions, but vertebral osteomyelitis is
      even rarer.

PMID- 8132372
TI  - Prolonged meningoencephalitis due to Epstein-Barr virus with favorable outcome in
      a young infant.
AB  - We present a case of meningoencephalitis due to EBV in a 2-month-old infant,
      without mononucleosis, which persisted for more than 5 months. Evidence for
      persistence of the infection was provided by a convulsive disorder and prolonged
      CSF pleocytosis, combined with persistent moderate anemia. Despite the
      persistence of the infection, the child continued to develop normally. This case
      demonstrates that EBV meningoencephalitis occurring in young patients may present
      with only subtle clinical findings and may have a favorable prognosis.

PMID- 8132373
TI  - A case of rhinoscleroma cured with ciprofloxacin.
AB  - The diagnosis of rhinoscleroma was confirmed in a 17-year-old female patient from
      Tehran, Iran, suffering from a roundish tumour of the nose. Prior treatment with
      streptomycin and tetracycline had been unsuccessful. A three-month course of high
      dose oral ciprofloxacin (750 mg b.i.d.) led to prompt cessation of the growth of
      the granuloma which was removed later by plastic surgery. Although serology alone
      appeared to have little value for the specific diagnosis of rhinoscleroma, a
      significant increase of IgG antibodies during treatment with ciprofloxacin
      confirmed infection by Klebsiella rhinoscleromatis in this case.

PMID- 8132374
TI  - MIC and serum bactericidal activity of clindamycin against methicillin-resistant
      and -sensitive staphylococci.
AB  - Six volunteers were given 600 mg clindamycin intravenously to investigate the
      serum bactericidal activity (SBA) against 50 methicillin susceptible (MSSA) and
      50 methicillin resistant Staphylococcus aureus (MRSA) strains. Minimal inhibitory
      concentrations (MIC) against MSSA, MRSA and 50 methicillin resistant strains of
      Staphylococcus epidermidis (MRSE), of which 50% were slime-producing, were
      determined. SBA of clindamycin against MSSA and MRSA was equally high (mean
      reciprocal SBA titer against MSSA vs MRSA 1 h after application was 13.0 vs
      13.45), although MICs against MRSA were markedly higher than against MSSA (MIC 90
      of MRSA vs MSSA: 0.06 vs > 32 mg/l). There was no difference in MICs between
      slime- and non-slime-producing MRSE.

PMID- 8132375
TI  - Hepatitis B and C infection in an institution for the mentally handicapped.

PMID- 8132377
TI  - Treatment of male infertility--what does the future hold?

PMID- 8132376
TI  - Safety and efficacy of ciprofloxacin in paediatric patients--review.
AB  - Like all fluoroquinolones, ciprofloxacin causes articular damage in juvenile
      animals. Consequently, this drug was not recommended for children or pregnant
      women. However, due to its antibacterial effectiveness and convenience of oral
      administration, ciprofloxacin is now increasingly used for the treatment of
      certain infectious conditions in children and adolescents aged less than 18
      years. In this paper the published literature on this subject is reviewed. Up to
      now, data are available on more than 1,500 paediatric patients who were given
      ciprofloxacin, two-thirds of whom were suffering from acute infectious
      bronchopulmonary exacerbations of cystic fibrosis, mainly due to Pseudomonas
      aeruginosa. The effectiveness of oral ciprofloxacin for this indication compared
      well to that of standard intravenous combination regimens. The majority of the
      remaining published trials was conducted in children with multiresistant typhoid
      fever; the administration of ciprofloxacin was successful in up to 100% of the
      cases. The safety profile of ciprofloxacin in children and adolescents was very
      similar to that observed in adult patients. Adverse events were noted in 5-15%,
      with gastrointestinal, skin and central nervous system reactions being the most
      common. Reversible arthralgia occurred in 36 out of 1,113 patients with cystic
      fibrosis, and in no case could cartilage damage be demonstrated by radiographic
      procedures. Thus, publication data clearly suggest that the administration of
      ciprofloxacin to children is effective and safe, but there is a need for further
      prospective, well-controlled clinical trials.

PMID- 8132378
TI  - Separation of human spermatozoa with hyaluronic acid induces, and Percoll
      inhibits, the acrosome reaction.
AB  - The effect on the acrosome reaction of human spermatozoa of two widely used sperm
      separation media, hyaluronic acid (Sperm Select) and Percoll, was studied. Viable
      and highly motile fractions of human spermatozoa were separated from seminal
      plasma using self-migration on a Percoll gradient. After translocation of
      separated spermatozoa from the Percoll solution to a culture medium, serum,
      Percoll or hyaluronic acid (Sperm Select) was added to aliquots of the
      spermatozoa containing culture medium. At increasing time intervals, the influx
      of 45Ca2+ into spermatozoa was measured and the concentration of viable
      spermatozoa that had undergone the acrosome reaction was analysed using the
      triple stain technique. Serum was found to be necessary to support sperm motility
      and viability. Compared to culture medium with serum only, addition of hyaluronic
      acid induced influx of 45Ca2+ and the acrosome reaction, whilst Percoll inhibited
      both of these actions. Hyaluronic acid (Sperm Select) added to spermatozoa
      separated by a 'swim-up' method induced, and the addition of Percoll inhibited,
      influx of 45Ca2+ when compared to the addition of culture medium with serum only.
      This study demonstrates that both hyaluronic acid (Sperm Select) and Percoll
      affect the acrosome reaction and the prerequisite for Ca2+ influx in human
      spermatozoa. These effects should be taken into consideration when using these
      media for preparation of spermatozoa for insemination or for fertilization in
      vitro.

PMID- 8132379
TI  - Sperm function in Indonesian men treated with testosterone enanthate.
AB  - This study was undertaken to assess the fertilizing capacity (sperm function) of
      residual spermatozoa produced by groups of men (n = 7) rendered oligozoospermic
      by treatment with weekly intramuscular injection of 50 or 100 mg testosterone
      enanthate (TE). The treatment was continued for 6 months and the effects compared
      with a control group (n = 6) in which men received weekly intramuscular
      injections of sesame oil (1 ml). Sperm function was assessed by tests of membrane
      integrity (supravital stain and hypoosmotic swelling [HOS] test) and sperm
      penetration (artificial cervical capillary tube test). The quality of sperm
      movement was also assessed. These parameters of sperm function were all reduced
      consistently in a dose-dependent manner with maximal suppression occurring
      between weeks 15 and 25 of treatment, and full recovery to baseline levels by 12
      months after cessation of treatment. The decrease in sperm function was
      correlated with the degree of suppression of sperm output with the proportion of
      morphologically normal spermatozoa and the degree of suppression of gonadotrophin
      levels. The weekly dose of 50 mg TE induced severe oligozoospermia (concentration
      < 5 million/ml) in four of seven men, whereas 100 mg TE induced azoospermia in
      all seven men by week 20. It is concluded that, unlike published observations on
      men of European background, the administration of TE at 100 mg per week may
      achieve adequate contraceptive efficacy in Indonesian men.

PMID- 8132380
TI  - Effect of age on seminiferous tubule protein secretion and the adverse effects of
      testicular toxicants in the rat.
AB  - This study has assessed the effect of age on protein secretion by seminiferous
      tubules (ST) isolated from rats and their response to Sertoli cell toxicants. ST
      were isolated from immature (aged 28 days), late pubertal (aged 45 days) and
      young adult (aged 70 days) rats and cultured in vitro for 24 h with 35S
      methionine in the presence or absence of FSH (1 mg/ml), m-dinitrobenzene (m-DNB)
      or nitrobenzene (NB) (both at 10(-4)M). Incorporation of 35S-methionine into
      newly synthesized proteins in the culture medium (secreted proteins) was assessed
      and the pattern of protein secretion evaluated using two-dimensional sodium
      dodecylsulphate polyacrylamide gel electrophoresis (2-D SDS-PAGE). These data
      were compared with those obtained using cultures of immature rat Sertoli
      cells+germ cells (SC+GC). Addition of FSH, m-DNB or NB in vitro either had no
      effect (NB) or had a small stimulatory effect (FSH and m-DNB) on the
      incorporation of 35S-methionine into overall secreted proteins by ST isolated
      from immature rats. At the same doses, addition of either FSH, m-DNB or NB to
      SC+GC co-cultures resulted in increased incorporation of radiolabel into secreted
      proteins in all instances. In contrast, the same additions to ST isolated from
      adult rats resulted in a 20-34% decrease in the overall incorporation of 35S
      methionine into secreted proteins. ST isolated from late pubertal rats showed a
      similar response to adult rats except that the decreases in incorporation induced
      by FSH, m-DNB and NB were smaller. Analysis by 2-D SDS-PAGE revealed considerable
      age-dependent differences in the proteins secreted by ST from immature and adult
      rats, of which 13 were identified as being of potential importance. Most of these
      proteins were prominent secretory products of ST from adult rats, but were minor
      or non-detectable products of cultures of ST or SC+GC from immature rats. Most of
      these proteins disappeared or decreased in abundance after culture of ST with m
      DNB or NB. Two proteins showed the reverse pattern, being more prominent
      secretory products in immature than mature rats, and their secretion was
      unaffected or was increased by toxicant exposure. These results demonstrate that
      there are major age-dependent differences in the secretion of total and specific
      proteins by isolated ST and that these are probably related to changes in the
      germ cell complement with age.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8132381
TI  - The gubernaculum in adult female, adult male and TFM male mice.
AB  - There is still controversy over whether androgens are involved in gubernacular
      migration during descent of the testis, prompting a review of anatomical events
      controlled by androgens. The gubernacular position in adult female, male, and
      testicular feminized male (TFM) mice (with complete androgen resistance) was
      observed macroscopically to determine its caudal limit and whether the adult TFM
      male still contained guvernacular bulk. The length of the processus vaginalis was
      measured, and the presence of a differentiated cremaster muscle was determined
      histologically. In 10 adult female mice there was neither a processus vaginalis
      nor a cremaster muscle, and the gubernaculum (round ligament of the ovary)
      attached to the external inguinal ring. In 10 adult TFM mice the gubernaculum
      ended at or just beyond the external ring, and was present in an amount
      corresponding to its size at the end of the outgrowth phase of development, with
      secondary infiltration by fat. The processus vaginalis was poorly developed, the
      cremaster muscle was undifferentiated, and there was no eversion of the cremaster
      sac. In 10 normal adult male mice the gubernaculum and testis had migrated to the
      scrotum, and the gubernaculum had regressed fully. Because gubernacular
      development in the androgen-resistant mouse cases after termination of
      transabdominal testicular migration, the anatomy of the adult confirms that, in
      the mouse, normal androgenic function is essential for eversion of the cremaster
      sac and gubernacular migration beyond the groin to the genital folds.

PMID- 8132382
TI  - Job exposure matrices in industry.
AB  - Job exposure matrices (JEM) are designed to link information on occupation with
      information on exposure to specific workplace hazards. In spite of some
      limitations, JEM are particularly useful in large retrospective epidemiological
      studies. The development of JEM designed for a company or an industrial sector
      have a more specific field of application than JEM used in population-based
      studies, and can therefore be based on a more detailed classification of
      occupations and better exposure information. This article reviews on-going
      research related to the design of JEM in support of industry-based studies. The
      review covers design aspects related to the structure of JEM, and specially the
      four main axes that may produce differences on exposure characteristics: agent
      (exposure), job, time and place. Attention has also been given to the different
      sources of information on exposure, the characteristics of the exposure and the
      validation of exposure estimates.

PMID- 8132383
TI  - Retrospective evaluation of the exposure to polycyclic aromatic hydrocarbons:
      comparative assessments with a job exposure matrix and by experts in industrial
      hygiene.
AB  - This work aimed at assessing the validity of job exposure matrix (JEM) for the
      retrospective evaluation of exposure to polycyclic aromatic hydrocarbons (PAH)
      within the framework of population-based case-control studies, taking the
      evaluation of industrial hygiene experts as reference. For this purpose, we used
      a case-control study for which the different levels of exposure were assessed by
      such experts after case by case evaluation of all job periods reported by the
      subjects. The JEM was applied to this set of data so that we had, according to
      job periods, the experts' evaluation on the one hand, and the JEM evaluation on
      the other. JEM sensitivity and specificity of the matrix vary widely from 0.13 to
      0.96 and 0.58 to 0.99 respectively, depending on whether the experts chose a
      narrow or wide definition of exposure and on the cutoff point chosen to
      dichotomize the JEM. We also computed, according to the sensitivity and
      specificity of the JEM, the odds ratio (OR) and relative efficiency (RE) given by
      the JEM for several hypothetical OR and frequencies of exposure among the
      controls. These calculations were made for different definitions of exposure by
      the experts and different cutoff points for the JEM. The results show a bias in
      the JEM's evaluation of the OR. In addition, the RE varies widely from very low
      values to high values (0.05-0.45) depending on the experts' definition of
      exposure and the cutoff point chosen for the matrix. Note, however, that all
      these calculations were made taking the experts' evaluation as the
      reference.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132384
TI  - Sources of discrepancies between a job exposure matrix and a case by case expert
      assessment for occupational exposure to formaldehyde and wood-dust.
AB  - Two methods used for retrospective evaluation of occupational exposures, a case
      by case assessment by expert and the application of a job exposure matrix (JEM),
      are compared using occupational histories collected for a case-control study on
      sinonasal cancer. The objective was to identify the main sources of discrepancies
      and to contribute to an optimal use of a JEM for population-based case-control
      studies. Comparisons were based on job periods, and were performed separately for
      two substances: formaldehyde and wood-dust. Job periods were classified according
      to the category of exposure assigned by the matrix, and to the probability and
      level of exposure assessed by the study expert. The sources of discrepancies were
      examined for job periods probably or definitely exposed according to the JEM and
      unexposed for the expert, or unexposed in the JEM and probably or definitely
      exposed to medium or high level for the expert. Such discrepancies were observed
      for 8% of the job periods for formaldehyde and 3% of the job periods for wood
      dust. The agreement between the two approaches was better for wood-dust than for
      formaldehyde. The relative importance of different sources of discrepancies was
      not the same for formaldehyde and wood-dust. For formaldehyde a substantial part
      of the discrepancies was due to disagreements between the study expert and the
      matrix experts, which were mostly differences in threshold limits between 'not
      exposed' and 'definitely exposed at a low level'. Differences between experts'
      opinions did not explain the discordances observed for wood-dust. The presence of
      additional information in the questionnaire was an important source of
      discrepancy for the two substances.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132385
TI  - Standardization in the retrospective evaluation by experts of occupational
      exposure to organic solvents in a population-based case-control study.
AB  - Epidemiologists carrying out retrospective evaluation of occupational exposure to
      solvents often use experts to assist in drawing up and interpreting structured
      questionnaires. However the epidemiologist cannot pass complete responsibility to
      the expert for deciding on the relative importance of the different exposure
      variables. Expert assessment of exposure to organic solvents was carried out in a
      population-based case-control study. The process of expert evaluation was
      examined and the different steps in the process identified. This paper describes
      work in progress on the formalization of the rules that experts use to identify
      and quantify exposure.

PMID- 8132386
TI  - Retrospective assessment of exposure by experts: the example of formaldehyde,
      solvents and mineral oils among textile and metal workers.
AB  - The validity of retrospective assessment of occupational exposure greatly depends
      on the amount of detail in the available information, on the knowledge of the
      specific industrial process by the experts, and on the criteria adopted to define
      relevant exposure. These criteria are difficult to standardize and are rarely
      made explicit in published reports, which makes it difficult to interpret
      inconsistencies among different studies. In two ongoing case-control studies on
      kidney cancer and, respectively, malignant lymphomas, a detailed occupational
      history was obtained and supplemented by 19 additional questionnaires,
      specifically addressing industrial activities where the knowledge of job title
      alone would have been insufficient for reliable exposure assessment. One further
      questionnaire was used to collect details of task and environment for all the
      other activities. These data are used to establish probability, intensity and
      frequency of exposure to 30 substances known or suspected to be carcinogenic from
      previous studies. There are two basic steps in the exposure assessment procedure:
      firstly, general rules are defined for each job within each activity covered by
      specific questionnaires; secondly the judgement is modulated according to the
      detailed tasks, working conditions and environment. To illustrate the process and
      to facilitate comparison with other studies, examples are given for a few common
      exposures in the textile and metal industries--the two most frequent economic
      activities in the study area--namely exposure to mineral oils, formaldehyde,
      aromatic solvents, chlorinated solvents and other organic solvents.

PMID- 8132387
TI  - Design of a job exposure matrix on electric and magnetic fields: selection of an
      efficient job classification for workers in thermoelectric power production
      plants.
AB  - Occupational exposure to 50 Hz electric and magnetic fields (EMF) was measured
      among 184 workers in thermoelectric power production plants using an individual
      portable dosimeter. A job exposure matrix (JEM) is elaborated from these data to
      be used in an epidemiological study on the potential carcinogenic effects of EMF.
      To reduce the range of exposure misclassification in the study, groups of workers
      with high exposure homogeneity must be identified. Classifying the workers by
      type of plant yielded homogeneous exposure groups, especially for workers in non
      nuclear power plants. Workers in nuclear plants had higher mean exposure to
      magnetic fields, but the homogeneity of exposure was smaller. The exposure also
      differed between occupations, but the occupational title did not produce a
      uniform increase of exposure homogeneity within subgroups. It is concluded that
      the place of work is the most important determinant of exposure to magnetic
      fields for workers in thermoelectric power plants to be included in the JEM.

PMID- 8132388
TI  - Development and use of a welding process exposure matrix in a historical
      prospective study of lung cancer risk in European welders.
AB  - A welding process exposure matrix has been developed relating 13 welding process
      welded metal combinations to average exposure levels for total welding fumes,
      total chromium, chromium (VI) and nickel. Quantitative estimates were derived
      from consultation of literature sources and of some company data. This matrix was
      applied to the welding histories of 11,092 welders in the framework of an IARC
      multicentre study. When detailed welding history was not available at the
      individual level the average company welding practice profile was applied. No
      dose-response relationship emerged for lung cancer risk with cumulative dose of
      the carcinogens chromium (VI) and nickel for stainless steel welders. Dilution of
      the dose-response relationship could result from between-plant and within-plant
      variability, and exposure in jobs not accounted for in the study, but not from
      the partial use of company versus individual data. It is also possible that there
      is no increased risk related to chromium and nickel exposure in this group of
      workers. Matrix exposure estimates would need to be validated and the matrix
      possibly refined by comparison with a variety of comprehensive welding exposure
      data sets.

PMID- 8132389
TI  - The risk of lung cancer from asbestos among Swedish construction workers: self
      reported exposure and a job exposure matrix compared.
AB  - A total of 719 lung cancers were identified in a follow-up of 135,000 Swedish
      construction workers interviewed during 1971-1974 by occupational health nurses
      as part of a routine health check-up. These were analysed in a matched case
      control study nested within this cohort, to compare different methods of
      characterizing exposure to asbestos. Self-reported exposure was contrasted with a
      job exposure matrix (JEM) of five levels of exposure intensity, applied to the
      job at the time of health check-up. Smoking adjusted odds ratios were computed
      and the JEM performed better than self-reported exposure, in being able to
      discriminate high risk subgroups. The same pattern was evident in a parallel
      analysis of 41 mesotheliomas. However both measures appeared subject to
      misclassification, and the question put seemed to pick up the use of asbestos
      cement products more effectively than asbestos insulation products. It is
      concluded that a simple JEM can be more reliable than a simple question, but that
      both should be much more detailed, to take account of different types of asbestos
      exposure and their variation over time.

PMID- 8132390
TI  - A vine-growing exposure matrix in the Herault area of France.
AB  - In the Herault region of France, vineyards cover an area of 128,000 hectares (60%
      of agricultural land) and involve more than 93% of farms. A vine-growing exposure
      matrix was built for assessing pesticide exposure. It is based on information
      obtained from a survey among 85 vine-growers who lived in Herault and who had
      detailed account books. This paper explains how this matrix was built and how to
      use it. It takes into consideration the calendar time (1950-1988), the type of
      products (powder, liquid) and the chemical classes. It can estimate the
      likelihood of exposure and the quantity of pesticide used. Such a matrix could be
      useful in epidemiological surveys in order to measure vine-growers' exposure to
      pesticides. Formulae are given to evaluate their mean exposure to these
      chemicals. Limitations of the matrix are discussed; it does not take into account
      several factors which might change exposure: temperature, wind speed, methods of
      application, use of protection, etc.

PMID- 8132391
TI  - Pesticide exposure assessment: a crop exposure matrix. The Working Group on
      Pesticide Exposure Assessment.
AB  - A crop exposure matrix (CEM) was developed in the context of two Italian case
      control studies. The CEM relates agricultural practices to pesticide exposures
      taking into account change over time and the use of chemicals by geographical
      area for farming. The matrix is specific to 14 areas and to 10 major crops. The
      exposure axis is made up of 440 chemicals used in the last 40 years in the areas
      of interest. In the matrix the association between crop growing and pesticides is
      expressed in terms of presence or absence of exposure. Accuracy of the matrix was
      initially evaluated using 26 occupational histories collected within the two case
      control studies. Sensitivity and specificity of CEM for some compounds were
      estimated versus assessment of exposure by experts. Sensitivity ranges from 83.3%
      to 100%, specificity from 66.2% to 95.8% depending on the chemicals.

PMID- 8132392
TI  - Exposure to solvents in the shoe and leather goods industries.
AB  - The shoe and leather goods industries are two of the main economic sectors in
      Tuscany. Organic solvents are the most important risk factors responsible for
      leukaemias and polyneuropathies. Job exposure matrices for solvents have been
      developed with two different aims: to contribute to the general matrix in
      different industries involving exposure to solvents and to provide a data source
      for use by health professionals. The matrices have been constructed on the basis
      of: scientific literature, notices of chemical compositions of trade products,
      technical reports collected by local services, the survey of a sample of
      industries in the province of Florence.

PMID- 8132393
TI  - Occupational epidemiology and assessment of exposure.

PMID- 8132394
TI  - Exposure assessment in a historical cohort of filling station attendants.
AB  - A historical cohort of service station attendants is underway. It is aimed at
      evaluating possible excess cancer risk in relation to exposure intensity. In this
      paper we discuss the feasibility of a retrospective exposure assessment by
      evaluating the association between indicators of workload and the exposure
      intensity to some aromatic hydrocarbons measured in a sample of current
      employees. Available for the analysis were 703 personal samples from 111 filling
      station workers. Measured concentrations of benzene, toluene and xylenes (8-hour
      time weighted averages) averaged 0.55 mg/m3, 0.71 mg/m3 and 0.32 mg/m3,
      respectively. The number of vehicles filled, the daily sales of super premium
      gasoline and motorbike fuel, and the winter season were all significant
      predictors of the log concentration of benzene in simple regression analyses. The
      size of the station acted as an effect modifier. While no single variable was
      able to predict the benzene level in large stations, for small stations an
      increase of 0.0579 and of 0.0418 in the log benzene concentration per unit
      increase in super premium gasoline (100 I) and in motorbike fuel (10 I)
      dispensed, was estimated. The overall variance explained by the multivariate
      model, however, was only 12.3%. Therefore, a clear categorization of groups with
      homogeneous and significantly different exposure levels is not achievable. From
      the point of view of exposure assessment, workers in small stations with higher
      sales of super premium gasoline tend to have higher exposure levels. This group
      should be examined in detail when the final results of the cohort study are
      available.

PMID- 8132395
TI  - Retrospective evaluation of occupational exposures in population-based case
      control studies: general overview with special attention to job exposure
      matrices.
AB  - Different approaches may be considered in the evaluation of past occupational
      exposures: questionnaires only, questionnaires and experts (such as industrial
      hygienists or occupational physicians), questionnaires and job exposure matrices
      (JEM). These approaches are described in this paper and their use in the
      framework of population-based case-control studies is discussed. The use of
      experts to assess exposure from questionnaires is generally considered to be the
      reference method. Its major drawbacks are its cost and the shortage of
      experienced experts. On the other hand, JEM reduce the cost of the study and
      provide an objective way of evaluating exposures. The main drawback of JEM is the
      fact that they can produce misclassification. The development of a JEM includes
      the choice of the job classification system which influences the degree to which
      the matrix can be used in other studies, the precise definition of exposures, and
      the choice of entries which provide more information than the oversimplified
      exposed/non-exposed dichotomy. Recent results on JEM methodology (statistical
      methods of analysis and evaluation of JEM quality) should encourage both their
      development and their use in epidemiological studies.

PMID- 8132396
TI  - Studying the performance of a job exposure matrix.
AB  - During the last decade, the use of job exposure matrices (JEM) in occupational
      studies has grown but uncertainty remains among epidemiologists and industrial
      hygienists regarding this methodology and appropriate methodological tools are
      needed to study the performance of JEM. It must first be emphasized that a true
      validation can rarely be achieved and that the performance of a JEM must be
      tested against the exposure evaluation of another method taken as a reference,
      such as expert assessment. This comparison comprises three main elements: the
      ability of the JEM to evaluate accurately the exposure itself, its statistical
      performances in terms of bias and power and its ability to detect known
      associations between risk factors and disease. When comparing JEM and experts,
      all aspects of the two methods have to be looked at and a balance struck between
      the advantages and shortcomings of each of them. The problem should not be
      reduced to a trade-off between the precision provided by experts and the cost
      savings possible by using JEM. Finally, it is important to avoid a systematic
      opposition between JEM and expert assessments, as one positive result of their
      comparison may be the improvement of both methods of exposure evaluation.

PMID- 8132397
TI  - Retrospective evaluation of occupational exposure to organic solvents:
      questionnaire and job exposure matrix.
AB  - Correct retrospective assignment of subjects to an exposure category is affected
      by a variety of problems: 1) lack of an objective lifetime measurement; 2)
      dependence upon the accuracy and thoroughness of the job description; 3) heavy
      reliance upon the knowledge of experts. The aim of the study was the
      quantification of the performance of a job exposure matrix (JEM) in evaluating
      solvent exposure, using expert judgements as the reference method. The sources of
      discrepancies between the two methods were analysed within the framework of two
      community-based case-control surveys. One included 765 cases of bladder cancer
      (BC) and 765 controls, the other 298 cases of glomerulonephritis (GN) and 298
      controls. The JEM had been set up previously for a case-control study on
      laryngeal cancer and is based on 4000 discrete job titles. Comparison between the
      JEM and expert exposure evaluation was carried out for 2736 job periods in the BC
      study and 929 in the GN study. Categories of exposure for both experts and JEM
      were dichotomized, using different cutoff points for exposure and non-exposure.
      Prevalence of exposure as assessed by the experts was twice as high in the GN
      study (19%) as in the BC study (10%), showing the importance of the questionnaire
      design and of the inclusiveness of the definition of exposure. Sensitivity of the
      JEM vis-a-vis the experts was low (23-63%), whereas specificity was rather high
      (87-98%). The best concordance between the two methods was obtained with a
      specific dichotomy from the JEM and a narrow definition of exposure by the
      experts. Bias and loss of power resulting from JEM misclassifications were
      calculated with a theoretical population odds ratio of 3 and an exposure
      prevalence of 10%. If the experts' classification of the subjects according to
      exposure is assumed to be 100% correct, using the JEM led to a bias in estimating
      the odds ratio, ranging from 1.5 to 2.1, and to a loss of power equivalent to a
      reduction in the number of subjects by a factor of 5 to 10. Analysis of
      systematic discrepancies between exposure assessments of the experts and the JEM
      showed that they were clustered with some job categories and arose from different
      sources: 1) inadequate job descriptions, related to the codification system
      adopted and necessitating the gathering of information at the individual level;
      2) true disagreements between JEM and experts regarding the definition of solvent
      exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8132398
TI  - Retrospective assessment of asbestos exposure--I. Case-control analysis in a
      study of lung cancer: efficiency of job-specific questionnaires and job exposure
      matrices.
AB  - Retrospective assessment of asbestos exposure--I. Case-control analysis in a
      study of lung cancer: efficiency of job-specific questionnaires and job exposure
      matrices. International Journal of Epidemiology 1993; 22 (Suppl. 2): S83-S95. In
      a lung cancer study in Northern Germany the asbestos exposure assessment obtained
      from detailed supplementary questionnaires (SQ) was compared to the assessment
      obtained by the application of two job exposure matrices (JEM) to the job
      history. The study includes 391 incident male cases and the same number of
      controls from the general population, matched by sex, age, and region. Almost 16%
      of the subjects are considered as never having been exposed to asbestos and 24%
      are classified as certainly exposed according to both of the JEM, the
      corresponding percentages of the SQ-method being 68% and 32%. Sixty percent are
      considered by the JEM as having an intermediate probability of exposure. In
      general, the agreement between the different methods is better when the exposure
      definition is restricted to definite exposures, the corresponding Kappa statistic
      being 0.67 for the comparison between both JEM and 0.44/0.39 between the JEM and
      the SQ. The positive agreement between SQ and JEM (reference) increases from 12%
      and 17% for subjects with low probability of exposure to 61% and 69% for those
      with definite exposures. A ranking according to cumulative exposure shows some
      dose-response relationship for each of the three methods with a smoking-adjusted
      OR in the highest category of 1.85 (95% CI: 1.01-3.38) for the SQ method and 2.47
      (95% CI: 1.40-4.37) and 2.94 (95% CI: 1.73-4.99) for the two JEM. The results are
      discussed with reference to the conceptual differences between the methods and
      their potential scope in future studies.

PMID- 8132399
TI  - Retrospective assessment of asbestos exposure--II. At the job level:
      complementarity of job-specific questionnaire and job exposure matrices.
AB  - Retrospective assessment of asbestos exposure--II. At the job level:
      Complementarity of job-specific questionnaire and job exposure matrices.
      International Journal of Epidemiology 1993; 22 (Suppl. 2): S96-S105. The
      assessments of asbestos exposure by two a priori job exposure matrices (JEM) and
      by a job-specific questionnaire (SQ) are compared at job level. The data used for
      the comparison were generated by an ongoing case-control study on lung cancer in
      a region of northern Germany with a relatively high past prevalence of asbestos
      exposure. Among job periods assessed as unexposed by either JEM, 96% are
      recognized as such by the SQ. Discrepancies between the SQ and JEM were observed
      in jobs rated potentially exposed by the JEM. Despite varying estimates, the JEM
      and SQ were consistent as regards the relative classification of job periods by
      probability of exposure. The concordance of the methods, estimated by Kappa
      statistics, was stronger for the two JEM than for either of the JEM and the SQ.
      The identification of specific occupation/industry combinations in which
      discrepancies were most frequent and the comparison with expert ratings in some
      jobs yield insights into the sources of the disagreement between the methods. The
      misclassification of exposure by the JEM usually results in an overestimation of
      exposure. This is essentially related to loss of information due to the use of
      job codes as surrogates for job task descriptions and to the insufficiency of
      published data on asbestos exposure in different industries. As regards the SQ,
      two main sources of potential loss of sensitivity were identified: 1) possible
      omission of indirect sources of exposure by this method, 2) possible
      incompleteness of the SQ. The present comparison of methods of asbestos exposure
      assessment does not allow any one approach to be considered superior to another.
      Indeed, as proposed by Ahrens et al. in Part I of the study, both should be used
      to ensure optimal epidemiological performance.

PMID- 8132400
TI  - Pathogenetic mechanisms in combined cilioretinal artery and retinal vein
      occlusion: a reappraisal.
AB  - We examined nine patients who presented cilioretinal artery occlusion (CLRAO)
      associated with retinal vein occlusion (RVO). CLRAO was probably secondary to the
      raised intraluminal resistance consequent to the RVO in patients showing
      initially a delayed filling of the cilioretinal artery in fluorescein
      angiography. Interestingly, these patients presented an ophthalmoscopically more
      severe form of RVO and had systemic predisposing factors for a RVO. In patients
      presenting a physiological perfusion of the cilioretinal artery in fluorescein
      angiography, RVO was a self limited disease and etiologic factors were not found.
      This may suggest that in these patients the CLRAO probably occurred
      simultaneously with the RVO after a decrease in perfusion pressure in both
      retinal and cilioretinal arterial systems. In this combined vaso-occlusive
      retinopathy the vulnerability of cilioretinal arteries can be explained either by
      the absence of autoregulation or by their lower perfusion pressure gradient in
      comparison with retinal arteries.

PMID- 8132401
TI  - Causes of low vision and blindness in south western Saudi Arabia. A hospital
      based study.
AB  - The authors studied 1,681 consecutive patients who attended their ophthalmic
      outpatient clinics over a period of 12 months to determine the patients' visual
      acuity status and the causes of any visual loss. Using the World Health
      Organization criteria for definition of visual acuity status, 1004 (59.7%)
      patients had normal vision. Four hundred and thirty-one (25.6%) patients had low
      vision or visual impairment and 246 (14.6%) patients were blind. Twenty-eight
      (1.9%) patients had no light perception in both eyes. Cataract, both in isolation
      and co-existing with other ocular pathology, was the major cause of both low
      vision and blindness (58.5% and 81.7%, respectively). A concerted attack on
      cataract alone will markedly reduce blindness and low vision in this region.

PMID- 8132402
TI  - Diffuse and focal hyperaemia of the outer eye in patients with chronic renal
      failure.
AB  - In 8 of 57 patients with chronic renal failure that all had deposition of calcium
      salts in the limboconjunctival area, a focal hyperaemia of the conjunctiva was
      observed. This focal hyperaemia developed gradually around one or more greyish,
      slightly elevated, areas situated in the bulbar conjunctiva in the interpalpebral
      fissure. Clinically these lesions are very much alike inflamed pingueculae. Three
      patients showed a diffuse inflammatory reaction of the eye that was characterized
      by a waxy red episcleral and conjunctival hyperaemia extending beyond the
      palpebral fissure. The average value of the serum calcium concentration in these
      patients was particularly high and statistically significantly higher than in
      patients with calcification but without inflammatory signs and also higher than
      in patients that showed focal hyperaemia. In addition to the focal hyperaemia and
      the diffuse hyperaemia, we observed another diffuse hyperaemia located
      principally in the conjunctival tissue. This conjunctival redness often followed
      the focal hyperaemia associated with pingueculae or preceded the more acute fiery
      red episcleral hyperaemia, but it could also be present in isolation.

PMID- 8132403
TI  - Scleral damage: comparison of standard and modified diathermy electrodes.
AB  - Full-thickness scleral diathermy using a standard electrode causes significant
      scleral damage and necrosis. Use of a modified (Jabbour's) diathermy electrode
      appears to cause minimal scleral damage. We evaluated the scleral changes
      following transscleral diathermy application using standard and modified
      diathermy electrodes to the peripheral retina and ciliary body. Twelve Dutch
      belted pigment rabbits were used in our experiment. Three eyes each were
      subjected to transscleral diathermy using standard and modified electrodes to
      produce chorioretinal scars and cyclodestruction. Eyes were examined with the
      slit lamp and indirect ophthalmoscope at weekly intervals for 4 weeks. Light and
      transmission electron microscopy was performed 1 hour after diathermy application
      in 4 animals and in the remaining 8 animals at 4 weeks. Chorioretinal scarring
      and ciliary body atrophy were successfully induced with both types of electrodes.
      However, scleral damage was less severe in eyes treated with the modified
      electrode as compared with the standard electrode.

PMID- 8132404
TI  - Perfluorooctylbromide (PFOB) as a vitreous substitute in non-human primates.
AB  - We evaluated the toxicity of perfluorooctylbromide in the primate eye as a short
      term postoperative vitreous substitute. Four eyes of 4 African green monkeys
      underwent complete vitrectomy and vitreous replacement with 1.5-2.0 ml of PFOB.
      One additional animal received BSS as a control vitreous substitute in one eye.
      Animals were examined twice weekly for clarity and consistency of the vitreous
      replacement substance. Anterior segment and lenses remained clear in all eyes,
      although in the immediate postoperative period one eye became inflamed and had a
      culture-negative vitritis. The other eyes showed a minimal anticipated
      postoperative vitreous inflammation. Emulsification of the PFOB began within 3
      days of injection and progressed up to 3 weeks, precluding fundus examination and
      fluorescein angiography after 2 weeks. Eyes were enucleated and light microscopy
      performed at 2 days, 10 days, 33 days, and 45 days. No toxic effects to the
      retinal cells were detectable by histological examination, but perivasculitis of
      retinal vessels was noted at 45 days. Indirect examination was normal up to 10
      days; thereafter, the fundus view was obscured by the emulsified PFOB. Because of
      cellular migration into the vitreous cavity and retinal perivasculitis, observed
      histologically, PFOB seems most suitable for intraoperative rather than
      postoperative use.

PMID- 8132405
TI  - Cataract surgery at district hospital level.
AB  - Cataract remains the leading cause of blindness worldwide, curable though, by a
      simple procedure. The backlog of cataract patients in developing countries is
      mounting despite sustainable and downright efforts by health ministries,
      international voluntary and non-governmental organisations [1]. The current
      situation has put many developing countries in a difficult dilemma. The authors
      present a review of a pilot-project in decentralised eye-care in Mutasa District,
      Zimbabwe. Cataract surgery is performed by a district general doctor as an
      alternative to clearing the cataract back-log in developing countries, as
      suggested in several studies [2-5]. It is important to persuade the health
      ministries to adopt this simple and cheap policy [6,7].

PMID- 8132406
TI  - Ophthalmic manpower in India--need for a serious review.
AB  - An attempt has been made to estimate the number of ophthalmic surgeons (OSs) in
      India, their distribution amongst the constituent states/union territories, and
      imbalances in the urban (big and small cities) and rural areas. With an
      ophthalmic surgeon:population ratio of 1:107,000 (similar to that in the UK), an
      increasing amount of blindness in India, the output by ophthalmic surgeons
      continues to be low. Whereas the shortage of surgeons has been recognised as a
      critical problem by the National Programme for Control of Blindness,
      recommendations made at various forums have been restricted only to increasing
      production of existing surgeons. The key issues relating to OSs in India are
      uneven distribution, under utilisation and increasing demands on the
      ophthalmologist's time, due to advancement in clinical ophthalmology in recent
      years. Serious intervention to streamline distribution and improve utilisation of
      OSs in government and private sectors is necessary to effectively counter the
      current menace of blindness. Another option-creating an exclusive cadre of
      cataract surgeons trained to perform intracapsular cataract extraction (ICCE) for
      a period of four months in the medical colleges--has been recommended.

PMID- 8132408
TI  - Chondroid syringoma of the eyelid.
AB  - An 81-year-old man underwent excisional biopsy of a big cylindric painless mass
      of the right lower eyelid, which had been present for over 23 years.
      Histopathologic and immuno-histochemical examination showed a chondroid
      syringoma, an uncommon benign neoplasm of possible eccrine sweat gland origin,
      which occurs generally in the head and neck skin. In the eyelids, it has been
      previously described as a small nodule in the upper lid. Surgical excision of
      these tumours is recommendable because malignant transformation is possible,
      although rare.

PMID- 8132407
TI  - Post-traumatic transient cortical blindness.
AB  - Five patients: three children, one adolescent, and one young adult, examined in
      an emergency room setting were diagnosed with post-traumatic transient cortical
      blindness. This syndrome is characterized by transient visual loss, normal
      pupillary response and normal funduscopic examination following minor head
      trauma. In each case, vision returned to normal within minutes to hours following
      injury, leaving no neurological sequelae. Headache, confusion, irritability,
      anxiety, nausea and vomiting were the most common related symptoms. While the
      mechanism responsible for the transient blindness is unknown, most authors
      propose an abnormal vascular response to trauma with resultant transient hypoxia
      and cerebral dysfunction. The similarity between the symptoms accompanying this
      syndrome and those seen during a classic migraine attack has led many
      investigators to suggest a common underlying pathophysiology. The purpose of this
      report is to highlight the salient clinical features and diagnostic approaches to
      this syndrome, thereby providing ophthalmologists and emergency room physicians a
      heightened awareness of this entity and the means to detect it.

PMID- 8132409
TI  - Phacolytic glaucoma and lens-induced uveitis.
AB  - The pathogenesis of lens-induced uveitis and phacolytic glaucoma is still not
      fully understood. The authors report a case of a 62-year-old white female, with
      bilateral lens dislocation into the vitreous, who presented clinical and
      pathological features of phacolytic glaucoma in the left eye. The ultrastructural
      study of aqueous and vitreous aspirates showed lenticular fragments and
      macrophages with lipofuscin granules and phagocytic vacuoles containing lens
      proteins. Immunocytochemistry revealed foamy macrophages immunoreactive for CD68
      and HLA-DR. One year later the right eye disclosed a mild anterior granulomatous
      uveitis with corneal mutton-fat keratic precipitates that remained unchanged in
      the course of sixteen months follow-up without further treatment. These findings
      corroborate the possibility that, besides their mechanical and inflammatory roles
      in the impairment of the outflow system of the (exciting) left eye, phacolytic
      macrophages might also have been involved in the afferent phase of the mild
      chronic uveitis of the (fellow) right eye.

PMID- 8132410
TI  - Differential rates of forgetting from long-term memory in Alzheimer's and multi
      infarct dementia.
AB  - In this study we explored the rate of forgetting from long-term memory in
      Alzheimer's (AD) and multi-infarct (MID) dementia. For this purpose, we
      administered to 15 AD, 15 MID, and 22 control subjects two tasks exploring,
      respectively, long-term verbal and long-term visuo-spatial memory. The absolute
      rate of forgetting in both tasks was computed as the difference between immediate
      and delayed recall of memorandum. Since level of immediate recall was
      significantly different between groups, a proportional rate of forgetting
      (percentage of memorandum lost passing from immediate to delayed recall) was
      computed for each patient. In the verbal task (Rey's 15 words) AD patients
      displayed significantly larger absolute and proportional rates of forgetting than
      MID and control subjects. In the spatial task (Corsi block supraspan), the
      absolute rate of forgetting was only marginally different between groups.
      Nevertheless, AD patients demonstrated a larger proportional rate of forgetting
      than MID and normal subjects. These results point out an exalted decay of
      information from long-term memory store in AD patients. In the light of previous
      data (Corkin et al., 1984; Kopelman, 1985) we propose that long-term memory
      deficits in AD is due, at least in part, to an abnormal forgetting of information
      within the first few minutes following acquisition. Information still present in
      the subsequent period (10 min to several days) is retained normally. The normal
      rate of forgetting in MID patients, further, suggests different mechanisms
      underlying memory disorders in vascular and degenerative dementias.

PMID- 8132412
TI  - Event-related potential asymmetries in children during pattern and phonemic
      processing of letters.
AB  - Event-related potentials (ERPs) were recorded at left and right anterior
      temporal, temporal, and parietal sites from ten children (mean age 10.45 years)
      during three tasks. In the detection task every letter required a response; in
      the form and rhyme discrimination tasks, a response was required to letters
      without an enclosed area or to those that did not rhyme with 'e', respectively.
      For all tasks, N170 peak latency was later at right temporal sites and was more
      negative in amplitude at right anterior temporal locations than homologous left
      locations. Also, left-right difference waveforms indicated that right hemisphere
      ERPs were more negative than the left at 200, 300 and 470 ms for most sites.
      These lateral differences may reflect a differential activation of the
      hemispheres during letter processing. Differences among the conditions were most
      evident for the latest positive peak at 475 ms in which detection resulted in
      shorter latencies and smaller amplitudes than the discrimination tasks.

PMID- 8132411
TI  - A meta-analysis of homovanillic acid concentrations in schizophrenia.
AB  - The results of several experiments in which homovanillic acid (HVA)
      concentrations were measured, mainly in the cerebrospinal fluid, of
      schizophrenics are examined using Fisher's combination procedure. It is found
      that the data does not support the claim that the level of this dopamine
      catabolite is raised whereas some evidence strongly supports the claim that it is
      actually lowered. This finding is discussed in relation to the hypothesis of
      dopaminergic neuronal hyperactivity in schizophrenia.

PMID- 8132413
TI  - The effects of oxygenated free radicals on VEP spectral components in
      experimental diabetes.
AB  - In this experimental research, 33 Swiss albino rats were studied. They were
      divided into three equal groups as control, alloxan-diabetic (diabetic group) and
      alloxan-diabetic rats treated with ginkgo biloba extract (diabetic-GbE group).
      After two months of diabetes and before ophthalmoscopically visible diabetic
      retinopathy, flash VEPs of three groups were recorded and spectral analysis of
      VEPs was computed by Fast Fourier Transform (FFT) algorithm. Comparing the
      results of diabetic and diabetic-GbE groups with control group, we observed a
      significant increase in the amplitude (dB) of 5 Hz frequency for the left and
      right responses of rats. At some frequencies, we also found important differences
      between diabetic-GbE and control groups.

PMID- 8132414
TI  - Acoustic and electrically elicited startle reaction: similar patterns of
      habituation and reflex modifications in humans.
AB  - The present study was performed in order to verify two relevant phenomena related
      to Startle Reaction in normal subjects: 1) the response habituation, that
      consists of an exponential decrement of the R2 component of Blink Reflex after
      repeated identical stimuli, and 2) the modification of R1 magnitude, R2 magnitude
      and latency when the startle eliciting stimulus is preceded by a warning
      stimulus. Our data confirm: 1) that habituation is independent of paradigm and
      type of stimulation (acoustic vs electrocutaneous), and 2) an electrical
      prestimulus has a facilitatory effect on the R2 latency of the electrically
      elicited Blink Reflex onset with an inhibition of R2 magnitude. The present study
      support the view of a systemic supramodal central mechanism of information
      processing and sensorial gating with super-imposable effects on the different
      sensorial pathways.

PMID- 8132415
TI  - Multistable visual perception induces a slow positive EEG wave.
AB  - Seven subjects observed a multistable pattern (stroboscopic alternative motion:
      SAM), and were instructed to press the button immediately after perceptual
      switching with the aim of detecting some neurophysiological parameters of EEG
      activity. Our results indicate that the EEG changes observed during multistable
      perception are similar to the family of event related potentials which we called
      perceptual switching related positivity. Furthermore, the frequency component of
      this potential has a similarity to the frequency content of stimulus locked P300.

PMID- 8132416
TI  - Sexual dimorphism in body and brain weight and its association with paw
      preference in cats.
AB  - Sexual dimorphism in body and brain weight was studied in cats. Paw preference
      was assessed by food reaching test. Sexual dimorphism in body weight related to
      paw preference. Males weighted more than females in total sample and non-right
      handed (NRH) cats (no significant difference in right-handed group). NRH males
      weighted more than right-handed (RH) males (no difference in females). Absolute
      total-brain weight did not show sexual dimorphism. Relative total-brain weight
      was sexually dimorphic only in NRH cats (females more than males). RH males
      weighted more than NRH males (no significant difference in females). Only
      absolute right-brain weighted more in males than females (total sample).
      Otherwise, no significant difference was found between absolute right- and left
      brain weights of male and female cats. The relative right- and left-brain
      weighted more in females than males only in NRH cats (no sexual dimorphism in RH
      cats); more in RH males than NRH males; no difference in RH and NRH females. The
      overall results indicated that sexual dimorphism in body and brain weight is
      associated with cerebral lateralization in cats.

PMID- 8132417
TI  - Maternal alcohol consumption before pregnancy and ultrastructure of neurons and
      interneuronal connections in rat offspring.
AB  - The ultrastructure of neurons and interneuronal connections in sensorimotor
      cortex have been studied in the offspring at 14- and 21-day-old female rats
      damaged by alcohol intoxication before pregnancy. We found three categories of
      ultrastructural changes in cortical neurons and interneuronal connections:
      delayed maturation of these structures, dystrophic and destructive changes and a
      signs of compensatory-adaptive processes. The first two categories of neuronal
      changes more marked at 14 days after birth. Later compensatory-adaptive changes
      become more significant, but dystrophic and destructive neuronal changes still
      remained. It is believed, that prenatal hypoxia-ischemia following alcohol
      consumption by female rats before pregnancy plays an important role in the
      pathogenesis of alcohol damage in cortical neurons and interneuronal connections
      in the offspring.

PMID- 8132418
TI  - The effects of unilateral forced nostril breathing on the heart.
AB  - Three experiments are described that employ impedance cardiography to monitor the
      effects of unilateral forced nostril breathing (UFNB) on the heart. Experiment 1
      includes 7 subjects (4 males, 3 females) with a respiratory rate of 6 breaths/min
      (BPM). Experiment 2 includes 16 trials using one subject to examine the
      intraindividual variability, at 6 BPM. Experiment 3 includes 10 trials with the
      same subject in experiment 2, but with a respiratory rate of 2-3 breaths/s. This
      rapid rate of respiration is a yogic breathing technique called "breath of fire"
      or "kapalabhatti" and employs a very shallow but rapid breath in which the
      abdominal region acts like a bellows. All 3 experiments demonstrated that right
      UFNB increases heart rate (HR) compared to left. Experiment 1 gave 7 negative
      slopes, or lowering in HR with left nostril breathing and 7 positive slopes, or
      increases in HR with right nostril breathing, p = .001. The second and third
      experiments showed differences in HR means in which right UFNB increases HR more
      than left, p = .013, p = .001, respectively. In experiment 2 stroke volume was
      higher with left UFNB, p = .045, compensating for lower HR. Left UFNB increased
      end diastolic volume as measured in both experiments 1 and 2, p = .006, p = .001,
      respectively. These results demonstrate a unique unilateral effect on sympathetic
      stimulation of the heart that may have therapeutic value.

PMID- 8132419
TI  - The effects of unilateral forced nostril breathing on cognitive performance.
AB  - This study describes the effects of 30 minutes of unilateral forced nostril
      breathing on cognitive performance in 51 right-handed undergraduate psychology
      students (25 males and 26 females). A verbal analogies task modeled after the
      Miller Analogies and SAT Tests was used as a test of left-hemispheric performance
      and mental rotation tasks based on the Vandenburg and Kuse adaptation of Shepard
      and Metzler's tests were used as spatial tasks for testing right-hemispheric
      performance. Spatial task performance was significantly enhanced during left
      nostril breathing in both males and females, p = .028. Verbal task performance
      was greater during right nostril breathing, but not significantly p = .14. These
      results are discussed in comparison to other cognitive and physiological studies
      using unilateral forced nostril breathing. This yogic breathing technique may
      have useful application in treating psychophysiological disorders with
      hemispheric imbalances and disorders with autonomic abnormalities.

PMID- 8132420
TI  - Serial determinations of leukocyte aggregation in patients with ischemic stroke.
AB  - The pattern of leukocyte aggregation and its possible relationship with the
      clinical outcome were evaluated in 35 untreated patients with acute
      cerebrovascular disease during each of the first three days of hospitalization.
      Although statistically significant differences were found when comparing patients
      and age and sex matched controls during any of the 3 days, a large overlapping of
      values was noted in each comparison. The overlapping was strongly reduced when
      the average 3-day value was compared. Similarly, when comparing subgroups of
      patients classified on the basis of their clinical status, the overlap of values
      observed during any of the 3 days dropped from 70% to 30% when considering the
      average 3-day levels of leukocyte aggregation. Furthermore, the level of
      correlation between leukocyte aggregation and size of cerebral infarction was
      better when considering the average 3-day value (p = .005) than the best single
      day correlation (p = .01). These data suggest that the association between acute
      cerebrovascular ischemia and leukocyte rheology is better discovered when
      repeated evaluation of the latter are performed.

PMID- 8132421
TI  - Differential effect of functional ablation of thalamic reticular nucleus on the
      acquisition of passive and active avoidance.
AB  - The possible contribution of inadvertent damage of the thalamic reticular nucleus
      to memory impairment caused by lesion of nucleus basalis magnocellularis (NBM)
      was examined. Rats carrying chronically implanted cannulae received unilateral
      injection of 3 ng tetrodotoxin (TTX) into the reticular nucleus either 60 min
      before (PRE) or 2 min after (POST) acquisition of a combined passive avoidance
      (PAR)--active avoidance (AAR) task. Three days later retrieval was tested during
      unilateral TTX blockade of the reticular nucleus in the same (IPSI) or in the
      opposite (CONTRA) hemisphere. Unilateral inactivation of the reticular nucleus
      affected neither acquisition nor retrieval of PAR, but interfered with AAR
      acquisition under the PRE conditions. AAR reacquisition was impaired in the PRE
      CONTRA but not in the other groups. The effects of reticular nucleus blockade
      (AAR disruption without PAR impairment) contrast with AAR facilitation and PAR
      disruption after NBM lesions. It is concluded that the consequences of NBM damage
      are not enhanced by unintentional thalamic encroachment.

PMID- 8132422
TI  - Sensory nerve conduction velocities are higher on the left than the right hand
      and motor conduction is faster on the right hand than left in right-handed normal
      subjects.
AB  - Lateralization in the sensory and motor nerve conduction velocities was studied
      in right-handed normal subjects. The nerve conduction velocities (NCVs) were
      measured in hands. Sensory NCVs were found to be higher on the left hand than the
      right hand. The motor NCVs did not show a statistically significant difference
      between the right and left hands. However, the motor conduction velocity measured
      from median nerve to the action potential from abductor pollicis brevis muscle
      was found to be significantly higher in the right hand than the left hand. It was
      concluded that fast conducting neuromuscular junctions on the right hand muscles
      would contribute to relatively fast right hand in right-handers. Relatively fast
      conducting sensory nerves in the left hand may contribute to a relatively better
      perception by the right cerebral hemisphere in right-handers.

PMID- 8132423
TI  - Reversal of visual neglect in Parkinson's disease by treatment with picoTesla
      range magnetic fields.
AB  - Visual neglect and impairment in perceptual motor or visuospatial tasks are among
      the most frequently encountered abnormalities in neuropsychological testing of
      patients with Parkinson's disease, being present in up to 90% of patients. It has
      been proposed that neglect reflects an attentional-arousal deficit induced by
      lesions that interrupt a cortical-limbic-reticular loop. Recently, we have
      reported that application of extracranial magnetic fields (MF) in the picoTesla
      range was efficacious in reducing the severity of the motor disability of
      Parkinsonism as well as improving some of the cognitive abnormalities associated
      with the disease such as visuoperceptive deficits. We now present a 61 year old
      fully medicated Parkinsonian patient in whom rapid reversal of left visual
      neglect as well as improvement in visuoconstructional (drawing) performance was
      noted immediately after a single external application of MF. We propose that this
      effect was related to enhancement of directed attention through a mechanism
      involving an interaction between the pineal gland, which is considered a
      "magnetosensor," and the reticular formation which mediates arousal and
      attention. This report demonstrates the efficacy of extremely weak MF in
      reversing some of the cognitive abnormalities in Parkinsonism, notably neglect
      and visuoperceptive deficits, which contribute significantly to impairment of the
      patient's daily living activities.

PMID- 8132424
TI  - Method in neurology.

PMID- 8132425
TI  - The neurological education of the primary physician.

PMID- 8132426
TI  - Teaching organization in the degree course in medicine.

PMID- 8132427
TI  - Teaching objectives.

PMID- 8132428
TI  - The neurology curriculum and modes of delivery.

PMID- 8132429
TI  - The teaching of neurology in the degree course in dentistry.
AB  - The problem of neurology teaching in the degree course in dentistry is addressed
      in the light of data gathered from teachers of the course. The first part of the
      paper deals with the teachers and the organization of the course, the second with
      the teaching objectives and relations with other disciplines and the third with
      the reform hypothesis of Table XVIII bis and the role of neurology in the
      curriculum of the dentistry school. The last part examines the assessment of
      teachers by students and the repercussions of improved teaching on attendance and
      attainment.

PMID- 8132430
TI  - The evaluation system in the degree course in medicine.

PMID- 8132431
TI  - The neurology specialist and functional disorders.

PMID- 8132432
TI  - Teacher training and permanent education.

PMID- 8132433
TI  - Survey of Italian neurological output in the three years 1989-1991.
AB  - On the wave of the furore over the haphazard approach to academic promotion in
      Italy and the role of published work in it, our analysis clears the role of the
      neurological publications in the three years 1989-1991. The data analysis,
      carried out by consulting on-line data bank and comparing the Italian production
      with that one of two sampled countries (France and Germany), shows that in the
      field of clinical neuroscience, this criticism is not in order.

PMID- 8132434
TI  - Classification of daily and near-daily headaches: proposed revisions to the IHS
      criteria.
AB  - The International Headache Society (IHS) headache classification, while a major
      advance, does not adequately classify the daily and near-daily headache disorders
      known as chronic daily headache (CDH). We believe that chronic daily headache is
      a group of disorders which includes chronic tension-type headache (CTTH),
      transformed migraine (TM), new daily persistent headache (NDPH), and hemicrania
      continua (HC). We propose specific criteria for transformed migraine, new daily
      persistent headache, and hemicrania continua, and have modified the criteria for
      chronic tension-type headache.

PMID- 8132435
TI  - Visceral pain threshold is deeply lowered far from the head in migraine.
AB  - A short-lasting over-distension of the hand-forearm veins, obtained through a non
      invasive original maneuver (Hand Arm Vein Distension test) induces local pain
      when applied to migraine sufferers in inter-critical period. Conversely, subjects
      with an absolutely negative personal and family history for any type of
      idiopathic headache do not report any pain or only an uncertain, slight one. The
      injection of 1 mL of 2% to 8% (i.e. 0.34 mol/L to 1.36 mol/L) hypertonic saline
      into the antecubital vein during an extemporary short (1 minute) circulatory
      blockage (ischemia induced to guarantee a strictly local action of the chemical
      stimulus) provokes moderate, strong or unbearable local (arm vein) pain in
      migraine sufferers but not in subjects with a personal and family history
      absolutely free from any type of headache. These results show for the first time
      that migraineurs show a proneness to visceral pain in viscera (veins) distant
      from the head (arm-hand). Such a finding is consistent with the theory that
      migraine pain is due to a central derangement of the viscerosensory system.

PMID- 8132436
TI  - Sulpiride and paroxetine in the treatment of chronic tension-type headache. An
      explanatory double-blind trial.
AB  - Drugs influencing monoaminergic pathways are of potential use in the treatment of
      pain. A serotonin re-uptake inhibitor, paroxetine (20-30 mg daily), and a
      dopamine antagonist, sulpiride (200-400 mg daily) were compared in a randomized,
      double-blind, response-conditional cross-over pilot study in 50 non-depressed
      patients with chronic tension-type headache. Headache was scored daily on a 5
      point verbal scale during 4-weeks baseline and during 8 weeks of treatment for
      each drug. A 5-point 'Global' assessment was obtained for each drug. In both
      treatment groups headache score decreased compared to baseline. Group comparison
      of 24 patients first treated with paroxetine and 24 patients first treated with
      sulpiride showed a non-significant trend in favor of sulpiride by 'Global'
      evaluation and by evaluation of the available diary records (18 paroxetine
      treated and 19 sulpiride-treated). Cross-over analysis of 'Global' records from
      20 patients treated with paroxetine followed by sulpiride and 17 patients treated
      in the reverse order showed better relief from sulpiride compared to paroxetine
      in patients having tested both drugs (P = .03). A similar difference was
      reflected in available headache scores (13 and 10 patients respectively; P =
      .03). Predominant side effects were sedation and depression, for paroxetine also
      nausea and head pain. None of the drugs improved headache more than one score
      point on average. A placebo controlled trial of sulpiride may be warranted.

PMID- 8132437
TI  - Chronic paroxysmal hemicrania and hemicrania continua: orbital phlebography and
      MRI studies.
AB  - Six patients with chronic paroxysmal hemicrania (CPH) and 10 patients with
      hemicrania continua (HC), two indomethacin-responsive, unilateral, headache
      syndromes, were investigated with orbital phlebography and magnetic resonance
      imaging of the brain. Orbital phlebography apparently showed pathological
      findings more frequently in CPH than in HC. Such abnormalities did not always
      show preference for the side of headache. MR scans were grossly normal in these
      headaches.

PMID- 8132438
TI  - Neuropeptide Y in juvenile migraine and tension-type headache.
AB  - Neuropeptide Y (NPY) is widely distributed throughout sympathetic nerve endings
      where it is co-stored and co-secreted with noradrenaline. It is considered a
      marker of noradrenergic function. To determine the role of NPY in the
      pathogenesis of juvenile headache, we determined its plasma levels in two groups
      of young migraine patients (with and without aura), in a group of episodic
      tension-type headache patients and in a group of age and sex-matched healthy
      subjects. Significantly lower plasma levels of NPY were evident in the migraine
      patients with aura (P < 0.001) and, to a lesser extent, in the migraine patients
      without aura (P < 0.02), both assessed in the interictal period, with respect to
      the control group. Plasma NPY levels tended to significantly increase during
      attacks in migraine patients with aura (P < 0.0009). A less evident, though
      significant increase was also present during attacks in migraine patients without
      aura (P < 0.02). No significant variations were observed between headache-free
      periods and attacks in tension-type headache patients. Reduced NPY levels in the
      interictal period can be considered further evidence of the derangement of the
      sympathetic function in the course of migraine, particularly that with aura. The
      increase in NPY levels during migraine attacks could be an expression of
      sympathetic activation, even though the functional status of this system is less
      efficient.

PMID- 8132439
TI  - Geomagnetic activity, humidity, temperature and headache: is there any
      correlation?
AB  - Meterological factors influence several biological functions. Geomagnetic
      activity (GMA) can be considered a trigger factor of migraine attacks. We studied
      the possible relationship between 40 migraine patients and some meteorological
      factors: humidity, temperature and geomagnetic activity in particular. All
      frequency changes of geomagnetic activity, temperature and humidity values are
      recorded daily. The study was performed from March to June 1988 over a
      geographically small area in order to avoid climatic and environmental
      influences. Our results indicate a significant correlation between geomagnetic
      activity and migraine attack frequency. Controversial opinions concerning the
      modalities of data collection and the possible relationships between environment
      and headache raise the need of further studies.

PMID- 8132441
TI  - Complicated retinal migraine.
AB  - Retinal migraine is not uncommon, but permanent sequelae are rare. We describe
      the case of a 23-year-old woman who had suffered from retinal migraine for five
      years. After a typical migraine attack a left nasal quadranopsia persisted.
      Fluorescein angiography showed a branch retinal arterial occlusion. Other causes
      were ruled out by appropriate laboratory techniques. Her visual field defect has
      persisted for eleven months.

PMID- 8132440
TI  - Chronic tension-type headache, mood depression and serotonin: therapeutic effects
      of fluvoxamine and mianserine.
AB  - Forty out-patients affected by chronic tension-type headache were selected
      according to the diagnostic criteria of International Headache Society (IHS)
      Headache Classification Committee. In a controlled trial patients received
      placebo for a four-week baseline period, then they were randomized in double
      blind fashion to therapy with mianserine (30-60 mg/day) of fluvoxamine (50-100
      mg/day) for another eight-week period. Frequency of headache, pain severity and
      analgesic consumption were evaluated using a self-monitoring system. Mood
      depression was evaluated at 0, 4 and 8 weeks by using Zung's Self-Rating
      Depression Scale and Hamilton Rating Scale for Depression. Both drugs were
      beneficial in the treatment of chronic tension-type headache. Non-depressed
      subjects with more severe headache responded best to fluvoxamine, whereas
      mianserine was more effective in the treatment of depressed patients with
      moderate headache. These results suggest that central serotoninergic
      neurotransmission can play a role in the pathophysiology of chronic tension-type
      headache also in non-depressed patients.

PMID- 8132442
TI  - Quantitative EEG in children with headache.
AB  - The object of this work is to determine if Brain Mapping can reveal significant
      differences between a normal control group and a group whose members suffer from
      one of three types of headache: tension-type, migraine with aura and migraine
      without aura. Both groups were formed by children aged between 6 and 14; the
      latter were undergoing no treatment and were in a headache-free phase. Results
      demonstrate that there are no significant differences between the control group
      and the tension-type headache group. Neither were differences found in migraine
      without aura group but in migraine with aura there was an increase of the
      theta/alpha ratio in the temporal posterior and occipital zones. This ratio could
      be used as a neurophysiological indicator in the evolution of the migraine with
      aura pathology.

PMID- 8132443
TI  - Basilar migraine with severe EEG abnormalities.
AB  - We report a patient suffering from a series of attacks fulfilling the criteria of
      basilar migraine. During the attack there was no normal EEG background pattern
      and the EEG showed predominantly delta activity. After the attack the EEG
      returned to (nearly) normal in a very short time. Up to now no such EEG findings
      have been reported in basilar migraine.

PMID- 8132444
TI  - Up-regulation of 5-HT2 serotonin receptor: a possible mechanism of transformed
      migraine.
AB  - Transformation of episodic migraine to chronic daily headache (so called
      transformed migraine) is now a well recognized phenomenon. Although several
      factors, i.e. analgesic overuse, increasing age, psychiatric disorders are
      reported to play some roles in this transformation, the precise cascade is still
      unclear. Further suppression of an already abnormal antinociceptive system with
      up-regulation of post-synaptic receptors is one of the possible explanation. In
      order to understand the mechanism underlying this condition, 5-HT2 serotonin
      receptors on platelets were assayed by the radioligand binding technique. Six
      transformed migraine patients (67.67 +/- 1.52 years) and seven healthy controls
      (72.86 +/- 1.82 years) were studied. [3H]-spiperone and ketanserin were used to
      determine the specific binding. We found a significant increase (P < 0.05) in the
      maximal receptor numbers (Bmax) on platelet membrane of the migraine patients
      when compared to the controls (64.31 +/- 11.06 and 39.96 +/- 5.42 fmol/mg
      protein, respectively), whereas the dissociation equilibrium constant (KD) values
      remained unchanged (3.63 +/- 0.78 nM and 2.84 +/- 0.48 nM for the migraine
      patients and controls, respectively). The up-regulation of serotonin receptors
      found in this study provided further support to the "serotonergic hypofunction"
      theory of migraine pathogenesis and may explain the unusual loss of episodicity
      seen in the transformed migraine patients.

PMID- 8132445
TI  - American Society of Andrology. 19th Annual meeting. Springfield, Illinois, March
      3-7, 1994. Abstracts.

PMID- 8132446
TI  - When similarity is a liability: effects of sex-based preferential selection on
      reactions to like-sex and different-sex others.
AB  - In 2 laboratory studies, 145 male and female undergraduates were selected for the
      role of manager either on the basis of merit or preferentially on the basis of
      their sex. Results of the first study indicated that when female subjects had
      been selected preferentially as compared with on a merit basis, they reacted more
      negatively to female (but not to male) applicants for an entry-level position in
      terms of personnel evaluations and competence ratings and they recommended female
      applicants for hire less frequently and less enthusiastically. No differences in
      personnel evaluations were found as a result of preferential selection when
      subjects were male (Study 1) or when subjects were provided with favorable
      information about their ability (Study 2). Implications for implementation of
      affirmative action programs are discussed.

PMID- 8132447
TI  - When to fix it and when to leave: relationships among perceived control, self
      efficacy, dissent, and exit.
AB  - Using a sample of hospital nurses, the author tested the hypothesis that both
      self-efficacy and perceived control over decision making contribute to
      individuals' willingness to engage in reformist dissent when faced with injustice
      and to their intentions to exit. Reformist dissent is defined as dissent that
      occurs within the confines of an organization's rules and norms. Perceived
      control over decision making was expected to be positively related to willingness
      to engage in reformist dissent and to be inversely related to exit. Because it
      was expected that both dissent and exit require confidence, self-efficacy was
      predicted to be positively related to both dissent and exit. Control was
      positively related to willingness to dissent and inversely related to exit. Self
      efficacy, however, predicted only dissent. Implications for worker well-being and
      retention are discussed, and directions for future research and theory
      development are offered.

PMID- 8132448
TI  - Sensing of aromatic compounds by the DmpR transcriptional activator of phenol
      catabolizing Pseudomonas sp. strain CF600.
AB  - The dmp operon of the pVI150 catabolic plasmid of Pseudomonas sp. strain CF600
      encodes the enzymes involved in the catabolism of phenol and methylphenols. The
      regulator of this dmp pathway, DmpR, is a member of the NtrC family of
      transcriptional activators and controls transcription of the dmp operon in
      response to aromatic effector compounds (V. Shingler, M. Bartilson, and T. Moore,
      J. Bacteriol. 175:1596-1604, 1993). Using a lux gene fusion reporter system, in
      which the DmpR-regulated operon promoter controls the expression of luciferase
      activity, we have shown in the study reported here that DmpR is activated by, but
      responds differentially to, the presence of a wide range of aromatic compounds.
      In many microbial regulatory systems, including some members of the NtrC family,
      the response to environmental fluctuations involves information transfer from
      surface sensory proteins to transcriptional regulators. However, DmpR-mediated
      activation of phenol metabolism in response to aromatic compounds occurs in the
      absence of a specific sensory protein. We used hybrids between DmpR and XylR, a
      structurally related regulator of toluene and xylene metabolism, to demonstrate
      that it is the amino-terminal domains of these regulators that determine the
      specificity of transcriptional activation. The results suggest that it is the
      direct interaction of aromatic compounds with the DmpR and XylR proteins that
      regulates their transcriptional promoting activity.

PMID- 8132449
TI  - YscN, the putative energizer of the Yersinia Yop secretion machinery.
AB  - Pathogenic yersiniae secrete a set of 11 antihost proteins called Yops. Yop
      secretion appears as the archetype of the type III secretion pathway. Several
      components of this machinery are encoded by the virA (lcrA) and virC (lcrC) loci
      of the 70-kb pYV plasmid. In this paper, we describe yscN, another gene involved
      in this pathway. It is the first gene of the virB locus. It encodes a 47.8-kDa
      protein similar to the catalytic subunits of F0F1 and related ATPases, as well as
      to products of other genes presumed to be involved in a type III secretion
      pathway. YscN contains the two consensus nucleotide-binding motifs (boxes A and
      B) described by Walker et al. (J. E. Walker, M. Saraste, M. J. Runswick, and N.
      J. Gay, EMBO J. 1:945-951, 1982). We engineered a pYV mutant encoding a modified
      YscN protein lacking box A. This mutant, impaired in Yop secretion, can be
      complemented in trans by a cloned yscN gene. We conclude that YscN is a component
      of the Yop secretion machinery using ATP. We hypothesize that it is either the
      energizer of this machinery or a part of it.

PMID- 8132450
TI  - Mutation of recF, recJ, recO, recQ, or recR improves Hfr recombination in
      resolvase-deficient ruv recG strains of Escherichia coli.
AB  - The formation of recombinants in Hfr crosses was studied in Escherichia coli
      strains carrying combinations of genes known to affect recombination and DNA
      repair. Mutations in ruv and recG eliminate activities that have been shown to
      process Holliday junction intermediates by nuclease cleavage and/or branch
      migration. Strains carrying null mutations in both ruv and recG produce few
      recombinants in Hfr crosses and are extremely sensitive to UV light. The
      introduction of additional mutations in recF, recJ, recO, recQ, or recR is shown
      to increase the yield of recombinants by 6- to 20-fold via a mechanism that
      depends on recBC. The products of these genes have been linked with the
      initiation of recombination. We propose that mutation of recF, recJ, recO, recQ,
      or recR redirects recombination to events initiated by the RecBCD enzyme. The
      strains constructed were also tested for sensitivity to UV light. Addition of
      recF, recJ, recN, recO, recQ, or recR mutations had no effect on the survival of
      ruv recG strains. The implications of these findings are discussed in relation to
      molecular models for recombination and DNA repair that invoke different roles for
      the branch migration activities of the RuvAB and RecG proteins.

PMID- 8132451
TI  - Some properties of HU are modified after the infection of Escherichia coli by
      bacteriophage T4.
AB  - Escherichia coli HU, an abundant, nucleoid-associated, DNA-binding protein, plays
      a role in several biological processes including DNA replication. Many other
      bacteria have well-conserved HU homologs, and there are several more-distantly
      related members of the family, including TF1, encoded by Bacillus subtilis phage
      SPO1. We have asked whether coliphage T4, like SPO1, encodes an HU homolog or
      whether it alters the properties of host HU. We have been unable to detect a T4
      specified HU homolog, but we have shown that E. coli HU extracted from phage
      infected cells differs in some properties from that extracted from uninfected
      cells. First, HU from uninfected cells inhibits a reconstituted T4 DNA
      replication system, whereas HU from infected cells does not. Second, HU from
      infected cells appears to bind a T4-encoded polypeptide, as shown by
      coimmunoprecipitation. We propose that such binding alters HU function in T4
      infected cells.

PMID- 8132452
TI  - Oscillating behavior of carbohydrate granule formation and dinitrogen fixation in
      the cyanobacterium Cyanothece sp. strain ATCC 51142.
AB  - It has been shown that some aerobic, unicellular, diazotrophic cyanobacteria
      temporally separate photosynthetic O2 evolution and oxygen-sensitive N2 fixation.
      Cyanothece sp. ATCC strain 51142 is an aerobic, unicellular, diazotrophic
      cyanobacterium that fixes N2 during discrete periods of its cell cycle. When the
      bacteria are maintained under diurnal light-dark cycles, N2 fixation occurs in
      the dark. Similar cycling is observed in continuous light, implicating a
      circadian rhythm. Under N2-fixing conditions, large inclusion granules form
      between the thylakoid membranes. Maximum granulation, as observed by electron
      microscopy, occurs before the onset of N2 fixation, and the granules decrease in
      number during the period of N2 fixation. The granules can be purified from cell
      homogenates by differential centrifugation. Biochemical analyses of the granules
      indicate that these structures are primarily carbohydrate, with some protein.
      Further analyses of the carbohydrate have shown that it is a glucose polymer with
      some characteristics of glycogen. It is proposed that N2 fixation is driven by
      energy and reducing power stored in these inclusion granules. Cyanothece sp.
      strain ATCC 51142 represents an excellent experimental organism for the study of
      the protective mechanisms of nitrogenase, metabolic events in cyanobacteria under
      normal and stress conditions, the partitioning of resources between growth and
      storage, and biological rhythms.

PMID- 8132453
TI  - Treponema pallidum rare outer membrane proteins: analysis of mobility by freeze
      fracture electron microscopy.
AB  - Freeze-fracture and deep-etch electron microscopy were used to investigate the
      molecular architecture of the Treponema pallidum outer membrane (OM). Freeze
      fracture electron microscopy of treponemes freshly harvested from rabbit testes
      revealed that the intramembranous particles (IMPs) in both the concave and convex
      OM leaflets were distributed into alternating areas of relatively high and low
      particle density; in many OM fractures, IMPs formed rows that ran either parallel
      to or obliquely across the fracture faces. Statistical analysis (runs test)
      confirmed that the IMPs were nonrandomly distributed in both OM leaflets.
      Examination of deep-etched specimens revealed that the particles observed in
      freeze-fractured OMs also were surface exposed. Combined analysis of deep-etched
      and cross-fractured treponemes revealed that the OM particles were located in
      regions of the OM away from the endoflagella and closely apposed to the
      cytoplasmic membrane-peptidoglycan complex. When treponemes were incubated for
      extended periods with heat-inactivated immune rabbit syphilitic serum, no
      alteration in the distribution of OM IMPs was detected. In further experiments,
      approximately 1:1 mixtures of T. pallidum and Escherichia coli or separate
      suspensions of the nonpathogenic Treponema phagedenis biotype Reiter were fixed
      at 34 degrees C or after cooling to 0 degree C (to induce lateral phase
      separations that would aggregate IMPs). Only particles in the T. pallidum OM
      failed to aggregate in cells fixed at the lower temperature. The combined data
      suggest that the mobility of T. pallidum rare OM proteins is limited, perhaps as
      a result of interactions between their periplasmic domains and components of the
      peptidoglycan-cytoplasmic membrane complex.

PMID- 8132454
TI  - Cell cycle-dependent transcription from the gid and mioC promoters of Escherichia
      coli.
AB  - Transcription from the gid and mioC promoters, which neighbor the origin of
      replication of the Escherichia coli chromosome (oriC), has been implicated in the
      control of initiation of replication of minichromosomes. The amounts of
      transcripts from these two promoters on the chromosome were quantified at various
      times in a synchronized culture of a temperature-sensitive dnaC mutant strain.
      Transcription from the gid promoter was most active before the initiation of
      replication and was inhibited after initiation, during the time corresponding to
      the period of sequestration of the oriC region from the dam methyltransferase. On
      the other hand, transcription from the mioC promoter was inhibited before
      initiation and the inhibition was relieved after initiation prior to the recovery
      of gid transcription. The strict regulation of transcription from the gid and
      mioC promoters may be involved in positive and negative control of chromosomal
      replication, respectively, as has been suggested for minichromosome replication.
      The DnaA protein was involved in repression of mioC transcription, indicating
      that the activity of the DnaA protein changes during the cell cycle.

PMID- 8132455
TI  - The virR gene, a member of a class of two-component response regulators,
      regulates the production of perfringolysin O, collagenase, and hemagglutinin in
      Clostridium perfringens.
AB  - The perfringolysin O (theta-toxin) gene (pfoA) of Clostridium perfringens was
      cloned into an Escherichia coli-C. perfringens shuttle vector, and the pfoA gene
      was expressed in mutants of C. perfringens 13 which lacked the production of
      perfringolysin O. One group (SI117) could express the pfoA gene, and the other
      (SI112) could not. A mutation in the regulatory system for pfoA gene expression
      was suspected in SI112. A chromosomal DNA library constructed from strain 13 was
      transformed into strain SI112 to identify the regulatory gene(s) for the pfoA
      gene. Five strains of 10,000 transformants restored perfringolysin O production.
      All contained a 2.5-kb DNA fragment. This fragment activated the transcription of
      the pfoA gene and also restored the production of collagenase (kappa-toxin) and
      hemagglutinin in strain SI112. Deletion analysis showed that a 1.25-kb region was
      sufficient for the trans activity, and sequence analysis disclosed that open
      reading frame 2 (ORF2) was located in this region. A homology search for the
      deduced amino acid sequence revealed that ORF2 was homologous to a response
      regulator in a two-component signal transduction system. ORF2 was designated
      virR, and it is suggested that the virR gene plays an important role in the
      pathogenicity of C. perfringens.

PMID- 8132456
TI  - Secretion of both partially unfolded and folded apoproteins of dimethyl sulfoxide
      reductase by spheroplasts from a molybdenum cofactor-deficient mutant of
      Rhodobacter sphaeroides f. sp. denitrificans.
AB  - Spheroplasts prepared from a molybdenum cofactor-deficient mutant of Rhodobacter
      sphaeroides f. sp. denitrificans secreted dimethyl sulfoxide (DMSO) reductase
      which had no molybdenum cofactor and therefore no activity, whereas those from
      wild-type cells secreted the active reductase. The inactive DMSO reductase
      proteins were separated by nondenaturing electrophoresis into two forms: form I,
      with the same mobility as the native enzyme, and form II, with slower mobility.
      Both forms had the same mobility on denaturing gel. Form I and active DMSO
      reductase had the same profile on gel filtration chromatography. Form II was
      eluted a little faster than the native enzyme, suggesting that DMSO reductase
      form II was not an aggregated form but a compactly folded form very similar to
      the native enzyme. Form II was digested by trypsin and denatured with urea,
      whereas form I was unaffected, like native DMSO reductase. These results
      suggested that form II was a partially unfolded but compactly folded apoprotein
      of DMSO reductase.

PMID- 8132457
TI  - A gene at 59 minutes on the Escherichia coli chromosome encodes a lipoprotein
      with unusual amino acid repeat sequences.
AB  - We report a 1.432-kb DNA sequence at 59 min on the Escherichia coli chromosome
      that connects the published sequences of the pcm gene for the isoaspartyl protein
      methyltransferase and that of the katF or rpoS (katF/rpoS) gene for a sigma
      factor involved in stationary-phase gene expression. Analysis of the DNA sequence
      reveals an open reading frame potentially encoding a polypeptide of 379 amino
      acids. The polypeptide sequence includes a consensus bacterial lipidation
      sequence present at residues 23 to 26 (Leu-Ala-Gly-Cys), four octapeptide proline
      and glutamine-rich repeats of consensus sequence QQPQIQPV, and four heptapeptide
      threonine- and serine-rich repeats of consensus sequence PTA(S,T)TTE. The deduced
      amino acid sequence, especially in the C-terminal region, is similar to that of
      the Haemophilus somnus LppB lipoprotein outer membrane antigen (40% overall
      sequence identity; 77% identity in last 95 residues). The LppB lipoprotein binds
      Congo red dye and has been proposed to be a virulence determinant in H. somnus.
      Utilizing a plasmid construct with the E. coli gene under the control of a phage
      T7 promoter, we demonstrate the lipidation of this gene product by the
      incorporation of [3H]palmitic acid into a 42-kDa polypeptide. We also show that
      treatment of E. coli cells with globomycin, an inhibitor of the lipoprotein
      signal peptidase, results in the accumulation of a 46-kDa precursor. We thus
      designate the protein NlpD (new lipoprotein D). E. coli cells overexpressing NlpD
      bind Congo red dye, suggesting a common function with the H. somnus LppB protein.
      Disruption of the chromosomal E. coli nlpD gene by insertional mutagenesis
      results in decreased stationary-phase survival after 7 days.

PMID- 8132459
TI  - Identification of bacteriophage T4 prereplicative proteins on two-dimensional
      polyacrylamide gels.
AB  - Bacteriophage T4 makes a large number of prereplicative proteins, which are
      involved in directing the transition from host to phage functions, in producing
      the new T4 DNA, and in regulating transcriptional shifts. We have used two
      dimensional gel electrophoresis (nonequilibrium pH gradient electrophoresis gels
      in the first dimension and sodium dodecyl sulfate-polyacrylamide gradient slab
      gels in the second) to identify a number of new prereplicative proteins. The
      products of many known genes are identified because they are missing in mutants
      with amber mutations of those genes, as analyzed by us and/or by previous
      workers. Some have also been identified by running purified proteins as markers
      on gels with labeled extracts from infected cells. Other proteins that are
      otherwise unknown are characterized as missing in infections with phage carrying
      certain large deletions and, in some cases, are correlated with sequence data.

PMID- 8132458
TI  - Mutations in firA, encoding the second acyltransferase in lipopolysaccharide
      biosynthesis, affect multiple steps in lipopolysaccharide biosynthesis.
AB  - The product of the firA (ssc) gene is essential for growth and for the integrity
      of the outer membrane of Escherichia coli and Salmonella typhimurium. Recently,
      Kelly and coworkers (T. M. Kelly, S. A. Stachula, C. R. H. Raetz, and M. S.
      Anderson, J. Biol. Chem., 268:19866-19874, 1993) identified firA as the gene
      encoding UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase, the third
      step in lipid A biosynthesis. We studied the effects of six different mutations
      in firA on lipopolysaccharide synthesis. All of the firA mutants of both E. coli
      and S. typhimurium examined had a decreased lipopolysaccharide synthesis rate. E.
      coli and S. typhimurium strains defective in firA produced a lipid A that
      contains a seventh fatty acid, a hexadecanoic acid, when grown at the
      nonpermissive temperature. Analysis of the enzymatic activity of other enzymes
      involved in lipid A biosynthesis revealed that the firA mutations pleiotropically
      affect lipopolysaccharide biosynthesis. In addition to that of UDP-3-O-(R-3
      hydroxymyristoyl)-glucosamine N-acyltransferase, the enzymatic activity of the
      lipid A 4' kinase (the sixth step of lipid A biosynthesis) was decreased in
      strains with each of the firA mutations examined. However, overproduction of FirA
      was not accompanied by overexpression of the lipid A 4' kinase.

PMID- 8132460
TI  - bop gene cluster expression in bacteriorhodopsin-overproducing mutants of
      Halobacterium halobium.
AB  - mRNA levels from the bop (bacterio-opsin), brp (bacterio-opsin-related protein),
      and bat (bacterio-opsin activator) genes in wild-type Halobacterium halobium and
      two bacteriorhodopsin-overproducing mutants (ET1001 and II-7) were quantitated
      under conditions in which oxygen levels were steadily depleted and then cultures
      were either kept in the dark or exposed to light. All three strains showed
      similar responses to depleted oxygen tensions and the lack of light: bop gene
      cluster transcript levels first increased in response to steadily declining
      oxygen, and once oxygen was depleted, transcript levels decreased and became
      undetectable within 20 to 40 h. In contrast, each strain responded differently to
      conditions of depleted oxygen and the presence of light. In the wild-type strain,
      bop gene cluster transcript levels increased 2.4- to 9.2-fold above the highest
      levels obtained in the dark. In mutant ET1001, bop gene cluster transcript levels
      did not increase above the highest levels obtained in the dark. In mutant II-7,
      bop and brp transcript levels did not increase above the highest levels obtained
      in the dark, but bat transcript levels increased approximately 5.7-fold. This
      differing response to identical physiological conditions indicates that the
      mutations resulting in the bacteriorhodopsin-overproducing phenotype in these two
      mutants are different.

PMID- 8132461
TI  - 13C nuclear magnetic resonance studies of Pseudomonas putida fatty acid metabolic
      routes involved in poly(3-hydroxyalkanoate) synthesis.
AB  - The formation of poly(3-hydroxyalkanoates) (PHAs) in Pseudomonas putida KT2442
      from various carbon sources was studied by 13C nuclear magnetic resonance
      spectroscopy, gas chromatography, and gas chromatography-mass spectroscopy. By
      using [1-13C]decanoate, the relation between beta-oxidation and PHA formation was
      confirmed. The labeling pattern in PHAs synthesized from [1-13C]acetate
      corresponded to the formation of PHAs via de novo fatty acid biosynthesis.
      Studies with specific inhibitors of the fatty acid metabolic pathways
      demonstrated that beta-oxidation and de novo fatty acid biosynthesis function
      independently in PHA formation. Analysis of PHAs derived from [1-13C]hexanoate
      showed that both fatty acid metabolic routes can function simultaneously in the
      synthesis of PHA. Furthermore, evidence is presented that during growth on medium
      chain-length fatty acids, PHA precursors can be generated by elongation of these
      fatty acids with an acetyl coenzyme A molecule, presumably by a reverse action of
      3-ketothiolase.

PMID- 8132462
TI  - DNA helicase requirements for DNA replication during bacteriophage T4 infection.
AB  - The lytic bacteriophage T4 uses multiple mechanisms to initiate the replication
      of its DNA. Initiation occurs predominantly at replication origins at early times
      of infection, but there is a switch to genetic recombination-dependent initiation
      at late times of infection. The T4 insertion-substitution system was used to
      create a deletion in the T4 dda gene, which encodes a 5'-3' DNA helicase that
      stimulates both DNA replication and recombination reactions in vitro. The
      deletion caused a delay in T4 DNA synthesis at early times of infection,
      suggesting that the Dda protein is involved in the initiation of origin-dependent
      DNA synthesis. However, DNA synthesis eventually reached nearly wild-type levels,
      and the final number of phages produced per bacterium was similar to that of the
      wild type. When the dda mutant phage also contained a mutation in T4 gene 59 (a
      gene normally required only for recombination-dependent DNA replication),
      essentially no DNA was synthesized. Recent in vitro studies have shown that the
      gene 59 protein loads a component of the primosome, the T4 gene 41 DNA helicase,
      onto DNA. A molecular model for replication initiation is presented that is based
      on our genetic data.

PMID- 8132463
TI  - DNA sequence divergence among derivatives of Escherichia coli K-12 detected by
      arbitrary primer PCR (random amplified polymorphic DNA) fingerprinting.
AB  - Derivatives of Escherichia coli K-12 of known ancestry were characterized by
      random amplified polymorphic DNA (RAPD) fingerprinting to better understand
      genome evolution in this family of closely related strains. This sensitive method
      entails PCR amplification with arbitrary primers at low stringency and yields
      arrays of anonymous DNA fragments that are strain specific. Among 150 fragments
      scored, eight were polymorphic in that they were produced from some but not all
      strains. Seven polymorphic bands were chromosomal, and one was from the F-factor
      plasmid. Five of the six mapped polymorphic chromosomal bands came from just 7%
      of the genome, a 340-kb segment that includes the terminus of replication. Two of
      these were from the cryptic Rac prophage, and the inability to amplify them from
      strains was attributable to deletion (excision) or to rearrangement of Rac. Two
      other terminus-region segments that resulted in polymorphic bands appeared to
      have sustained point mutations that affected the ability to amplify them. Control
      experiments showed that RAPD bands from the 340-kb terminus-region segment and
      also from two plasmids (P1 and F) were represented in approximate proportion to
      their size. Optimization experiments showed that the concentration of
      thermostable polymerase strongly affected the arrays of RAPD products obtained.
      Comparison of RAPD polymorphisms and positions of strains exhibiting them in the
      pedigree suggests that many sequence changes occurred in these historic E. coli
      strains during their storage. We propose that the clustering of such mutations
      near the terminus reflects errors during completion of chromosome replication,
      possibly during slow growth in the stab cultures that were often used to store E.
      coli strains in the early years of bacterial genetics.

PMID- 8132464
TI  - Identification of the bphA4 gene encoding ferredoxin reductase involved in
      biphenyl and polychlorinated biphenyl degradation in Pseudomonas sp. strain
      KKS102.
AB  - The nucleotide sequence of the downstream region of the bph operon from
      Pseudomonas sp. strain KKS102 was determined. Two open reading frames (ORF1 and
      ORF2) were found in this region, and the deduced amino acid sequence of ORF2
      showed homology with the sequences of four ferredoxin reductases of dioxygenase
      systems. When this region was inserted just upstream of the bph operon, which
      does not contain a gene encoding ferredoxin reductase, biphenyl dioxygenase
      activity was detected. The 24- and 44-kDa polypeptides predicted from the two
      open reading frames were identified by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Crude extract which contained the products of ORF2 and bphA1A2A3
      showed cytochrome c reduction activity. These data clearly suggest that ORF2
      encodes ferredoxin reductase. The deduced amino acid sequence of ORF1 does not
      show significant homology with the sequences of any other proteins in the SWISS
      PROT data bank, and the function of ORF1 is unknown.

PMID- 8132465
TI  - Effects of nitrate respiration on expression of the Arc-controlled operons
      encoding succinate dehydrogenase and flavin-linked L-lactate dehydrogenase.
AB  - Expression of sdhCDAB (encoding succinate dehydrogenase) and lctD (encoding the
      flavin-linked L-lactate dehydrogenase) is elevated aerobically and repressed
      anaerobically in Escherichia coli. The repression is initiated by
      autophosphorylation of the sensor protein ArcB, followed by phosphoryl group
      transfer to the regulator ArcA. ArcA-P, a global transcriptional regulator, then
      prevents sdh and lct expression. The stimulus for ArcB is not O2 deficiency per
      se. In vitro experiments showed that ArcB phosphorylation is enhanced by
      pyruvate, D-lactate, acetate, and NADH, the concentrations of which are likely to
      increase with the lack of an effective exogenous electron sink. In addition to
      their aerobic function, the two primary dehydrogenases also have roles in
      anaerobic nitrate respiration. Results presented here indicate that the increase
      of sdh and lct expression by nitrate depended on its chemical reduction, which in
      turn diminished the ArcA-P pool. Unexpectedly, a mutation in the fnr gene
      (encoding a global regulator involved in anaerobic metabolism) also alleviated
      the anaerobic repressions. Mutations in arcB or arcA were epistatic over that of
      fnr. Moreover, since this relief was counteracted by pyruvate in the growth
      medium, Fnr appears to affect formation of stimuli for ArcB. It is possible that
      Fnr also indirectly affects some of the other members of the arcA modulon, e.g.,
      cyoABCDE (encoding the cytochrome o complex), cydAB (encoding the cytochrome d
      complex), and sodA (encoding the manganese-dependent superoxide dismutase).

PMID- 8132466
TI  - The essential virulence protein VirB8 localizes to the inner membrane of
      Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens genetically transforms plant cells by transferring a
      specific DNA fragment from the bacterium through several biological membranes to
      the plant nucleus where the DNA is integrated. This complex DNA transport process
      likely involves membrane-localized proteins in both the plant and the bacterium.
      The 11 hydrophobic or membrane-localized proteins of the virB operon are
      excellent candidates to have a role in DNA export from agrobacteria. Here, we
      show by TnphoA mutagenesis and immunogold electron microscopy that one of the
      VirB proteins, VirB8, is located at the inner membrane. The observation that a
      virB8::TnphoA fusion restores export of alkaline phosphatase to the periplasm
      suggests that VirB8 spans the inner membrane. Immunogold labeling of VirB8 was
      detected on the inner membrane of vir-induced A. tumefaciens by transmission
      electron microscopy. Compared with that of the controls, VirB8 labeling was
      significantly greater on the inner membrane than on the other cell compartments.
      These results confirm the inner membrane localization of VirB8 and strengthen the
      hypothesis that VirB proteins help form a transfer DNA export channel or gate.

PMID- 8132467
TI  - 3-Carboxy-cis,cis-muconate lactonizing enzyme from Neurospora crassa: an
      alternate cycloisomerase motif.
AB  - 3-Carboxy-cis,cis-muconate lactonizing enzyme (CMLE; EC 5.5.1.5) from Neurospora
      crassa catalyzes the reversible gamma-lactonization of 3-carboxy-cis,cis-muconate
      by a syn-1,2 addition-elimination reaction. The stereochemical and regiochemical
      course of the reaction is (i) opposite that of CMLE from Pseudomonas putida (EC
      5.5.1.2) and (ii) identical to that of cis,cis-muconate lactonizing enzyme (MLE;
      EC 5.5.1.1) from P. putida. In order to determine the mechanistic and
      evolutionary relationships between N. crassa CMLE and the procaryotic
      cycloisomerases, we have purified CMLE from N. crassa to homogeneity and
      determined its nucleotide sequence from a cDNA clone isolated from a p
      hydroxybenzoate-induced N. crassa cDNA library. The deduced amino acid sequence
      predicts a protein of 41.2 kDa (365 residues) which does not exhibit sequence
      similarity with any of the bacterial cycloisomerases. The cDNA encoding N. crassa
      CMLE was expressed in Escherichia coli, and the purified recombinant protein
      exhibits physical and kinetic properties equivalent to those found for the
      isolated N. crassa enzyme. We also report that N. crassa CMLE possesses
      substantially reduced yet significant levels of MLE activity with cis,cis
      muconate and, furthermore, does not appear to be dependent on divalent metals for
      activity. These data suggest that the N. crassa CMLE may represent a novel
      eucaryotic motif in the cycloisomerase enzyme family.

PMID- 8132468
TI  - Acid and base resistance in Escherichia coli and Shigella flexneri: role of rpoS
      and growth pH.
AB  - Escherichia coli K-12 strains and Shigella flexneri grown to stationary phase can
      survive several hours at pH 2 to 3, which is considerably lower than the acid
      limit for growth (about pH 4.5). A 1.3-kb fragment cloned from S. flexneri
      conferred acid resistance on acid-sensitive E. coli HB101; sequence data
      identified the fragment as a homolog of rpoS, the growth phase-dependent sigma
      factor sigma 38. The clone also conferred acid resistance on S. flexneri
      rpoS::Tn10 but not on Salmonella typhimurium. E. coli and S. flexneri strains
      containing wild-type rpoS maintained greater internal pH in the face of a low
      external pH than strains lacking functional rpoS, but the ability to survive at
      low pH did not require maintenance of a high transmembrane pH difference. Aerobic
      stationary-phase cultures of E. coli MC4100 and S. flexneri 3136, grown initially
      at an external pH range of 5 to 8, were 100% acid resistant (surviving 2 h at pH
      2.5). Aerobic log-phase cultures grown at pH 5.0 were acid resistant; survival
      decreased 10- to 100-fold as the pH of growth was increased to pH 8.0. Extended
      growth in log phase also decreased acid resistance substantially. Strains
      containing rpoS::Tn10 showed partial acid resistance when grown at pH 5 to
      stationary phase; log-phase cultures showed < 0.01% acid resistance. When grown
      anaerobically at low pH, however, the rpoS::Tn10 strains were acid resistant. E.
      coli MC4100 also showed resistance at alkaline pH outside the growth range (base
      resistance). Significant base resistance was observed up to pH 10.2. Base
      resistance was diminished by rpoS::Tn10 and by the presence of Na+. Base
      resistance was increased by an order of magnitude for stationary-phase cultures
      grown in moderate base (pH 8) compared with those grown in moderate acid (pH 5).
      Anaerobic growth partly restored base resistance in cultures grown at pH 5 but
      not in those grown at pH 8. Thus, both acid resistance and base resistance show
      dependence on growth pH and are regulated by rpoS under certain conditions. For
      acid resistance, and in part for base resistance, the rpoS requirement can be
      overcome by anaerobic growth in moderate acid.

PMID- 8132469
TI  - Catabolite repression of the Bacillus subtilis xyl operon involves a cis element
      functional in the context of an unrelated sequence, and glucose exerts additional
      xylR-dependent repression.
AB  - Catabolite repression (CR) of xylose utilization by Bacillus subtilis involves a
      14-bp cis-acting element (CRE) located in the translated region of the gene
      encoding xylose isomerase (xylA). Mutations of CRE making it more similar to a
      previously proposed consensus element lead to increased CR exerted by glucose,
      fructose, and glycerol. Fusion of CRE to an unrelated, constitutive promoter
      confers CR to beta-galactosidase expression directed by that promoter. This
      result demonstrates that CRE can function independently of sequence context and
      suggests that it is indeed a generally active cis element for CR. In contrast to
      the other carbon sources studied here, glucose leads to an additional repression
      of xylA expression, which is independent of CRE and is not found when CRE is
      fused to the unrelated promoter. This repression requires a functional xylR
      encoding Xyl repressor and is dependent on the concentrations of glucose and the
      inducer xylose in the culture broth. Potential mechanisms for this glucose
      specific repression are discussed.

PMID- 8132470
TI  - Isolation, phenotypic characterization, and complementation analysis of mutants
      of Methylobacterium extorquens AM1 unable to synthesize pyrroloquinoline quinone
      and sequences of pqqD, pqqG, and pqqC.
AB  - Aerobic gram-negative methylotrophs oxidize methanol to formaldehyde by using a
      methanol dehydrogenase that has pyrroloquinoline quinone (PQQ) as a prosthetic
      group. Seventy-two mutants which are unable to grow on methanol unless the growth
      medium is supplemented with PQQ have been isolated in the facultative methanol
      utilizer Methylobacterium extorquens AM1. In addition, 12 previously isolated
      methanol oxidation mutants of M. extorquens AM1 were shown to be able to grow on
      methanol in the presence of PQQ. These putative PQQ biosynthesis mutants have
      been complemented by using previously isolated clones containing M. extorquens
      AM1 DNA, which were known to contain genes necessary for oxidation of methanol to
      formaldehyde (mox genes). Subcloning and transposon mutagenesis experiments have
      assigned these mutants to five complementation groups in two gene clusters.
      Representatives of each complementation group were shown to lack detectable PQQ
      in the growth medium and in cell extracts and to contain methanol dehydrogenase
      polypeptides that were inactive. Therefore, these mutants all appear to be
      defective in PQQ biosynthesis. PQQ biosynthesis mutants of Methylobacterium
      organophilum DSM 760 and M. organophilum XX were complemented by using M.
      extorquens AM1 subclones, and PQQ biosynthesis mutants of M. extorquens AM1 and
      M. organophilum XX were complemented by using M. organophilum DSM 760 subclones.
      This analysis suggested that a total of six PQQ biosynthesis complementation
      groups were present in M. extorquens AM1 and M. organophilum DSM 760. A 2-kb M.
      extorquens AM1 DNA fragment that complemented the MoxO class of PQQ biosynthesis
      mutants was sequenced and found to contain two complete open reading frames and
      the N-terminal sequence of a third. These genes designated pqqDGC, had predicted
      gene products with substantial similarity to the gene products of corresponding
      pqq genes in Acinetobacter calcoaceticus and Klebsiella pneumoniae. pqqD encodes
      a 29-amino-acid peptide which contains a tyrosine residue and glutamate residue
      that are conserved in the equivalent peptides of K. pneumoniae, PqqA (23 amino
      acids), and A. calcoaceticus, PqqIV (24 amino acids), and are thought to be the
      precursors for PQQ biosynthesis. The organizations of a cluster of five PQQ
      biosynthetic genes appear to be similiar in four different bacteria (M.
      extorquens AM1, M. organophilum DSM 760, K. pneumoniae, and A. calcoaceticus).
      Our results show that a total of seven pqq genes are present in M. extorquens
      AM1, and these have been designated pqqDGCBA and pqqEF.

PMID- 8132472
TI  - Easy cloning of mini-Tn10 insertions from the Bacillus subtilis chromosome.
AB  - Delivery vectors for mini-Tn10 transposons function in Bacillus subtilis (M. A.
      Petit, C. Bruand, L. Janniere, and S. D. Ehrlich, J. Bacteriol. 172:6736-6740,
      1990). Using this system, we identified a new gene (sytA) whose inactivation
      affected regulation of genes of sucrose metabolism. For cloning the sytA::Tn10
      insertion in Escherichia coli, we developed a methodology similar to that
      commonly used for B. subtilis Tn917 insertions. We constructed a plasmid which
      can be used to insert (by in vivo recombination) a ColE1 origin linked to a
      spectinomycin resistance gene (ori-spc element) into mini-Tn10 transposons
      inserted into the B. subtilis chromosome. DNA extracted from a sytA::Tn10::ori
      spc transformant was cut with restriction enzymes that do not cut into the
      Tn10::ori-spc sequence; plasmids containing the sytA::Tn10 insertion were cloned
      by self-ligation, followed by transformation of E. coli. To obtain the wild-type
      sytA region, one of these plasmids was ligated with an E. coli-B. subtilis
      shuttle vector conferring erythromycin resistance, and the hybrid was used to
      transform the wild-type B. subtilis strain. Erythromycin-resistant transformants,
      detected as spectinomycin sensitive, resulted from conversion of the insertion
      mutation by the resident wild-type locus. The shuttle plasmid containing the wild
      type locus could then be recovered in E. coli.

PMID- 8132471
TI  - Isolation of an R- M+ mutant of Yersinia enterocolitica serotype O:8 and its
      application in construction of rough mutants utilizing mini-Tn5 derivatives and
      lipopolysaccharide-specific phage.
AB  - A generally applicable procedure was used to isolate a spontaneous restriction
      deficient mutant of Yersinia enterocolitica serotype O:8. Transposition frequency
      in the mutant strain 8081-res was approximately 6.7 x 10(-6) per recipient, while
      it was practically zero in the wild-type strain 8081-c. Mobilization frequency
      into 8081-res was 10(5) times higher than that into the wild-type strain. The
      mutant had lost the ability to express the YenI restriction endonuclease activity
      present in serotype O:8 strains. This allowed the construction of a transposon
      library in 8081-res. Insertion mutants with transposons in the genes of the rfa
      region were selected from this library.

PMID- 8132473
TI  - Identification of the iroA gene product of Neisseria meningitidis as a
      lactoferrin receptor.
AB  - The iroA gene product is an iron limitation-inducible outer membrane protein of
      Neisseria meningitidis. A spontaneous mutant lacking the gene was unable to bind
      lactoferrin. Furthermore, Escherichia coli strains expressing the IroA protein
      were capable of binding lactoferrin. Apparently, the IroA protein functions as a
      lactoferrin receptor.

PMID- 8132474
TI  - Role of the purine repressor hinge sequence in repressor function.
AB  - A protease-hypersensitive hinge sequence in Escherichia coli purine repressor
      (PurR) connects an N-terminal DNA-binding domain with a contiguous corepressor
      binding domain. Binding of one molecule of dimeric repressor to operator DNA
      protects the hinge against proteolytic cleavage. Mutations in the hinge region
      impair repressor function in vivo. Several nonfunctional hinge mutants were
      defective in low-affinity binding to operator DNA in the absence of corepressor
      as well as in high-affinity corepressor-dependent binding to operator DNA,
      although binding of corepressor was similar to binding of the wild-type
      repressor. These results establish a role for the hinge region in operator
      binding and lead to a proposal for two routes to form the holoPurR-operator
      complex.

PMID- 8132475
TI  - Carbon source-dependent inhibition of xyl operon expression of the Pseudomonas
      putida TOL plasmid.
AB  - TOL plasmid-encoded degradation of benzyl alcohol by Pseudomonas putida is
      inhibited by glucose and other compounds related to the main carbohydrate
      metabolism in Pseudomonas species. We report here that this effect is exerted at
      the level of expression of the xyl catabolic operons, and two xyl promoters, Pu
      and Ps, were identified as the primary targets of this inhibition. xyl promoter
      activation was also inhibited by glucose in the heterologous Escherichia coli
      system, apparently not however by the classical mechanism of enteric catabolite
      repression.

PMID- 8132476
TI  - Isolation and characterization of the Rickettsia prowazekii recA gene.
AB  - The recA gene has been isolated from Rickettsia prowazekii, an obligate
      intracellular bacterium. Comparison of the amino acid sequence of R. prowazekii
      RecA with that of Escherichia coli RecA revealed that 62% of the residues were
      identical. The highest identity was found with RecA of Legionella pneumophila, in
      which 69% of the residues were identical. Amino acid residues of E. coli RecA
      associated with functional activities are conserved in rickettsial RecA, and the
      R. prowazekii recA gene complements E. coli recA mutants for UV light and methyl
      methanesulfonate sensitivities as well as recombinational deficiencies. The
      characterized region upstream of rickettsial recA did not contain a sequence
      homologous to an E. coli LexA binding site (SOS box), suggesting differences in
      the regulation of the R. prowazekii recA gene.

PMID- 8132477
TI  - Partition of nonreplicating DNA by the par system of bacteriophage P1.
AB  - P1 plasmid encodes a cis-acting centromere analog, parS, and two Par proteins
      that together stabilize plasmids by partitioning them to daughter bacteria. We
      infected immune bacteria with bacteriophage lambda into which parS had been
      inserted. The presence of P1 Par proteins in the infected cells was found to
      delay the appearance of cells cured of the nonreplicating, extrachromosomal
      lambda-parS DNA. This stabilization of lambda-parS, approximated in a computer
      simulation, demonstrates that active partition by the P1 par system does not
      require the act of plasmid replication and can be studied in its absence.

PMID- 8132478
TI  - Identification of the Methanococcus voltae S-layer structural gene.
AB  - We have established that the gene which we had previously identified as encoding
      the Methanococcus voltae P-type ATPase is, in fact, the structural gene for the
      M. voltae S-layer protein. This conclusion is based on a comparison of the N
      terminal sequence of S-layer protein prepared by two independent methods with
      that derived from the nucleotide sequence of the cloned gene. This conclusion was
      further supported by immunocytochemical localization of the antigen directed
      against the antibodies used in the cloning experiments.

PMID- 8132479
TI  - "Protease I" of Escherichia coli functions as a thioesterase in vivo.
AB  - Escherichia coli protease I is assayed as an esterase active with certain
      synthetic model chymotrypsin substrates. However, the gene encoding protease I
      has the same DNA sequence and genomic location as tesA, a gene that encodes E.
      coli thioesterase I. We report that both hydrolase activities utilize the same
      active site and demonstrate that the protein functions as a thioesterase in vivo.

PMID- 8132481
TI  - Analysis of type II polyketide beta-ketoacyl synthase specificity in Streptomyces
      coelicolor A3(2) by trans complementation of actinorhodin synthase mutants.
AB  - Complementation of defined actinorhodin beta-ketoacyl synthase (KS) mutants by
      various other KS genes suggested that the ORF1-encoded KS may be relatively
      generalized in function, whereas the ORF2-encoded KS component may provide
      specificity in polyketide chain construction. Evidence for differential temporal
      spatial expression of the actinorhodin and spore pigment KSs in Streptomyces
      coelicolor was obtained.

PMID- 8132480
TI  - Mapping and cloning of gldA, the structural gene of the Escherichia coli glycerol
      dehydrogenase.
AB  - gldA, the structural gene for the NAD(+)-dependent glycerol dehydrogenase, was
      mapped at 89.2 min on the Escherichia coli linkage map, cotransducible with, but
      not adjacent to, the glpFKX operon encoding the proteins for the uptake and
      phosphorylation of glycerol. gldA was cloned, and its position on the physical
      map of E. coli was determined. The expression of gldA was induced by
      hydroxyacetone under stationary-phase growth conditions.

PMID- 8132482
TI  - Mitochondrial anion transport systems. Minireview series.

PMID- 8132483
TI  - An introduction to the mitochondrial anion carrier family.

PMID- 8132484
TI  - The mitochondrial transport protein superfamily.
AB  - The ADP/ATP, phosphate, and oxoglutarate/malate carrier proteins found in the
      inner membranes of mitochondria, and the uncoupling protein from mitochondria in
      mammalian brown adipose tissue, belong to the same protein superfamily.
      Established members of this superfamily have polypeptide chains approximately 300
      amino acids long that consist of three tandem related sequences of about 100
      amino acids. The tandem repeats from the different proteins are interrelated, and
      probably have similar secondary structures. The common features of this
      superfamily are also present in nine proteins of unknown functions characterized
      by DNA sequencing in various species, most notably in Caenorhabditis elegans and
      Saccharomyces cerevisiae. The high level expression in Escherichia coli of the
      bovine oxoglutarate/malate carrier, and the reconstitution of active carrier from
      the expressed protein, offers encouragement that the identity of superfamily
      members of known sequence but unknown function may be uncovered by a similar
      route.

PMID- 8132485
TI  - Dialectics in carrier research: the ADP/ATP carrier and the uncoupling protein.
AB  - A concise review is given of the research in our laboratory on the ADP/ATP
      carrier (AAC) and the uncoupling protein (UCP). Although homologous proteins,
      their widely different functions and contrasts are stressed. The pioneer role of
      research on the AAC, not only for the mitochondrial but also for other carriers,
      and the present state of their structure-function relationship is reviewed. The
      function of UCP as a highly regulated H+ carrier is described in contrast to the
      largely unregulated ADP/ATP exchange in AAC. General principles of carrier
      catalysis as derived from studies on the AAC and UCP are elucidated.

PMID- 8132487
TI  - Mechanism and regulation of the mitochondrial ATP-Mg/P(i) carrier.
AB  - The mitochondrial ATP-Mg/P(i) carrier functions to modulate the matrix adenine
      nucleotide pool size (ATP + ADP + AMP). Micromolar Ca2+ is required to activate
      the carrier. Net adenine nucleotide transport occurs as an electroneutral
      divalent exchange of ATP-Mg2- for HPO4(2-). A steady-state adenine nucleotide
      pool size is attained when the HPO4(2-) and ATP-Mg2- matrix/cytoplasm
      concentration ratios are the same. This means that ATP-Mg2- can be accumulated
      against a concentration gradient in proportion to the [HPO4(2-)] gradient that is
      normally maintained by the P(i)/OH- carrier. In liver, changes in matrix adenine
      nucleotide concentrations that are brought about by the ATP-Mg/P(i) carrier can
      affect the activity of adenine nucleotide-dependent enzymes that are in the
      mitochondrial compartment. These enzymes in turn contribute to the overall
      regulation of bioenergetic function, flux through the gluconeogenesis and urea
      synthesis pathways, and organelle biogenesis. The ATP-Mg/P(i) carrier is distinct
      from other mitochondrial transport systems with respect to kinetics and to
      substrate and inhibitor sensitivity. It is the only carrier regulated by Ca2+.
      This carrier is present in kidney and liver mitochondria, but not in heart.

PMID- 8132486
TI  - Chemical, immunological, enzymatic, and genetic approaches to studying the
      arrangement of the peptide chain of the ADP/ATP carrier in the mitochondrial
      membrane.
AB  - In the process of oxidative phosphorylation, the exchange of cytosolic ADP3-
      against mitochondrial ATP4- across the inner mitochondrial membrane is mediated
      by a specific carrier protein. Two different conformations for this carrier have
      been demonstrated on the basis of interactions with specific inhibitors, namely
      carboxyatractyloside (CATR) and bongkrekic acid (BA). The two conformations,
      referred to as CATR and BA conformations, are interconvertible, provided that ADP
      or ATP are present. The functional ADP/ATP carrier is probably organized as a
      tetramer. In the presence of CATR or BA the tetramer is split into two dimers
      combined with either of the two inhibitors. The amino acid sequence of the beef
      heart carrier monomer (297 residues) contains three repeats of about 100 residues
      each. Experimental results obtained through different approaches, including
      photolabeling, immunochemistry, and limited proteolysis, can be interpreted on
      the basis of a model with five or six transmembrane alpha helices per carrier
      monomer. Two mobile regions involved in the binding of nucleotides and accessible
      to proteolytic enzymes have been identified. Each of them may be visualized as
      consisting of two pairs of short amphipathic alpha helices, which can be
      juxtaposed to form hydrophilic channels facilitating the nucleotide transport.
      Mutagenesis in yeast is currently being used to detect strategic amino acids in
      ADP/ATP transport.

PMID- 8132488
TI  - Phosphate transport in mitochondria: past accomplishments, present problems, and
      future challenges.
AB  - The requirement of inorganic phosphate (Pi) for oxidative phosphorylation in
      eukaryotic cells is fulfilled through specific Pi transport systems. The
      mitochondrial proton/phosphate symporter (Pic) is a membrane-embedded protein
      which translocates Pi from the cytosol into the mitochondrial matrix. Pic is
      responsible for the very rapid transport of most of the Pi used in ATP synthesis.
      During the past five years there have been advances on several fronts. Genomic
      and cDNA clones for yeast, bovine, rat, and human Pic have been isolated and
      sequenced. Functional expression of yeast Pic in yeast strains deficient in Pi
      transport and expression in Escherichia coli of a chimera protein involving Pic
      and ATP synthase alpha subunit have been accomplished. Pic, in contrast to other
      members of the family of transporters involved in energy metabolism, was
      demonstrated to have a presequence, which optimizes the import of the precursor
      protein into mitochondria. Six transmembrane segments appear to be a structural
      feature shared between Pic and other mitochondrial anion carriers, and recent
      site directed mutagenesis studies implicate structure-functional relationships to
      bacteriorhodopsin. These recent advances on Pic will be assessed in light of a
      more global interpretation of transport mechanism across the inner mitochondrial
      membrane.

PMID- 8132489
TI  - Transmembrane topology, genes, and biogenesis of the mitochondrial phosphate and
      oxoglutarate carriers.
AB  - Phosphate and oxoglutarate carriers transport phosphate and oxoglutarate across
      the inner membranes of mitochondria in exchange for OH- and malate, respectively.
      Both carriers belong to the mitochondrial carrier protein family, characterized
      by a tripartite structure made up of related sequences about 100 amino acids in
      length. The results obtained on the topology of the phosphate and oxoglutarate
      carriers are consistent with the six alpha-helix model proposed by Saraste and
      Walker. In both carriers the N- and C-terminal regions are exposed toward the
      cytosol. In addition, the oxoglutarate carrier has been shown to be a dimer by
      means of crosslinking studies. The bovine and human genes coding for the
      oxoglutarate carrier are split into eight and six exons, respectively, and five
      introns are found to the same position in both genes. The bovine and human
      phosphate carrier genes have the same organization with nine exons separated by
      eight introns at exactly the same positions. The phosphate carrier of mammalian
      mitochondria is synthesized with a cleavable presequence, in contrast to the
      oxoglutarate carrier and the other members of the mitochondrial carrier family.
      The precursor of the phosphate carrier is efficiently imported, proteolytically
      processed, and correctly assembled in isolated mitochondria. The presequence
      deficient phosphate carrier is imported with an efficiency of about 50% as
      compared with the precursor of the phosphate carrier and is correctly assembled,
      demonstrating that the mature portion of the phosphate carrier contains
      sufficient information for import and assembly into mitochondria.

PMID- 8132490
TI  - Structure, function and regulation of the tricarboxylate transport protein from
      rat liver mitochondria.
AB  - Recent progress is summarized on the structure, function, and regulation of the
      tricarboxylate (i.e., citrate) transport protein (CTP) from the rat liver
      mitochondrial inner membrane. The transporter has been purified and its
      reconstituted function characterized. A cDNA clone encoding the CTP has been
      isolated and sequenced, thus enabling a deduction of the complete amino acid
      sequence of this 32.6 kDa transport protein. Dot matrix analysis and sequence
      alignment indicate that based on structural considerations the CTP can be
      assigned to the mitochondrial carrier family. Hydropathy analysis of the
      transporter sequence indicates six putative membrane-spanning alpha-helices and
      has permitted the development of an initial model for the topography of the CTP
      within the inner membrane. The questions as to whether more than one gene encodes
      the CTP and whether more than one isoform is expressed remain unanswered at this
      time. Studies documenting a diabetes-induced alteration in the function of
      several mitochondrial anion transporters, which can be reversed by treatment with
      insulin, provide a physiologically/pathologically relevant experimental system
      for studying the molecular mechanism(s) by which mitochondrial transporters are
      regulated. Potential future research directions are discussed.

PMID- 8132491
TI  - The mitochondrial tricarboxylate carrier.
AB  - The tricarboxylate carrier has recently been purified from rat liver mitochondria
      by three distinct scientific groups using different methods. A 37-38-kDa protein
      has been prepared by silca gel 60 chromatography by our group (Claeys and Azzi,
      1989; Glerum et al., 1990). The specific citrate transport activity of this
      preparation is not significantly different from that measured in mitochondria and
      it is inhibitable by 1,2,3-benzenetricarboxylic acid. Bisaccia et al. (1990) have
      reported the isolation of a 30-kDa protein by Celite 535 chromatography, and
      Kaplan's group (Kaplan et al., 1990) have isolated a 32.5-kDa protein by Matrex
      Orange, Matrex Blue, and Affi-Gel chromatography. Peptide mapping has failed to
      support any structural homologies between the 37-38-kDa and the 30-32.5-kD
      proteins. The 38-kD protein is N-terminally blocked. The peptides obtained by
      several cleavage procedures have been partially sequenced. Their sequence
      information has been used to obtain different cDNA clones by a dual approach, the
      polymerase chain reaction and screening of a lambda ZAP cDNA library. The largest
      cDNA which could be isolated is 2,986 bp in length and contains a 1071-bp-long
      open reading frame and an unusually long 3' untranslated region, both of which
      have been completely sequenced. The protein sequence of the carrier from the
      first in-frame methionine is 322 amino acids in length and exhibits a molecular
      mass of 35,546. Comparison of the protein sequence to the sequences of the four
      members of the mitochondrial carrier protein family (ADP/ATP carrier, phosphate
      carrier, 2-oxoglutarate/malate carrier, and uncoupling protein) does not reveal
      significant similarity (cf. Walker et al., 1987). A tripartite internal homology,
      which is a characteristic of these proteins, is not present in the sequence of
      the tricarboxylate carrier protein. The mRNA for the tricarboxylate carrier is
      expressed in rat liver and brain, but not in rat heart.

PMID- 8132492
TI  - Functional properties of purified and reconstituted mitochondrial metabolite
      carriers.
AB  - Eight mitochondrial carrier proteins were solubilized and purified in the
      authors' laboratories using variations of a general procedure based on
      hydroxyapatite and Celite chromatography. The molecular mass of all the carriers
      ranges between 28 and 34 kDa on SDS-PAGE. The purified carrier proteins were
      reconstituted into liposomes mainly by using a method of detergent removal by
      hydrophobic chromatography on polystyrene beads. The various carriers were
      identified in the reconstituted state by their kinetic properties . A complete
      set of basic kinetic data including substrate specificity, affinity, interaction
      with inhibitors, and activation energy was obtained. These data closely resemble
      those of intact mitochondria, as far as they are available from the intact
      organelle. Mainly on the basis of kinetic data, the asymmetric orientation of
      most of the reconstituted carrier proteins were established. Several of their
      functional properties are significantly affected by the type of phospholipids
      used for reconstitution. All carriers which have been investigated in
      proteoliposomes function according to a simultaneous (sequential) mechanism of
      transport; i.e., a ternary complex, made up of two substrates and the carrier
      protein, is involved in the catalytic cycle. The only exception was the carnitine
      carrier, where a ping-pong mechanism of transport was found. By reaction of
      particular cysteine residues with mercurial reagents, several carriers could be
      reversibly converted to a functional state different from the various
      physiological transport modes. This "unphysiological" transport mode is
      characterized by a combination of channel-type and carrier-type properties.

PMID- 8132493
TI  - Effects of equisetin on rat liver mitochondria: evidence for inhibition of
      substrate anion carriers of the inner membrane.
AB  - The effect of equisetin, an antibiotic produced by Fusarium equiseti, has been
      studied on mitochondrial functions (respiration, ATPase, ion transport).
      Equisetin inhibits the DNP-stimulated ATPase activity of rat liver mitochondria
      and mitoplasts in a concentration-dependent manner; 50% inhibition is caused by
      about 8 nmol equisetin/mg protein. The antibiotic is without effect either on the
      ATPase activity of submitochondrial particles or on the purified F1-ATPase. It
      inhibits both the ADP- or DNP-activated oxygen uptake by mitochondria in the
      presence of glutamate+malate or succinate as substrates, but only the ADP
      stimulated respiration is inhibited if the electron donors are TMPD+ascorbate. It
      does not affect the NADH or succinate oxidation of submitochondrial particles.
      Equisetin inhibits in a concentration-dependent manner the active Ca(2+)-uptake
      of mitochondria energized both by ATP or succinate without affecting the Ca(2+)
      uniporter itself. The antibiotic inhibits the ATP-uptake by mitochondria (50%
      inhibition at about 8 nmol equisetin/mg protein) and the Pi and dicarboxylate
      carrier. It does not lower the membrane potential at least up to 200 nmol/mg
      protein concentration. The data presented in this paper indicate that equisetin
      specifically inhibits the substrate anion carriers of the mitochondrial inner
      membrane.

PMID- 8132494
TI  - Biophysical characterization of OprB, a glucose-inducible porin of Pseudomonas
      aeruginosa.
AB  - OprB, a glucose-inducible porin of P. aeruginosa, was characterized by black
      lipid bilayer analysis and circular dichroism spectroscopy. Black lipid bilayer
      analysis of OprB revealed a single-channel conductance of 25 pS, the presence of
      a glucose binding site with a Ks for glucose of 380 +/- 40 mM, and the formation
      of channels with a strong selection for anions. Analysis of P. aeruginosa OprB
      circular dichroism spectra revealed a high beta sheet content (40%) which is
      within the range of that determined for other porins. Values obtained from black
      lipid bilayer analysis were compared to those previously obtained for OprB of P.
      putida [Saravolac et al. (1991). J. Bacteriol. 173, 4970-4976] and indicated
      extensive similarities in the single-channel conductance and glucose-binding
      properties of these two porins. Immunological and amino terminal sequence
      analysis revealed a high degree of homology. Of the first 14 amino terminal
      residues, 12 were identical. A major difference between the two porins was found
      in their ion selectivity. Whereas P. aeruginosa OprB is anion selective, P.
      putida OprB and other carbohydrate selective porins are known to be cation
      selective.

PMID- 8132495
TI  - Calcium gating of H+ fluxes in chloroplasts affects acid-base-driven ATP
      formation.
AB  - In previous work, calcium ions, bound at the lumenal side of the CF0H+ channel,
      were suggested to keep a H+ flux gating site closed, favoring sequestered domain
      H+ ions flowing directly into the CF0-CF1 and driving ATP formation by a
      localized delta approximately mu H+ gradient. Treatments expected to displace
      Ca++ from binding sites had the effect of allowing H+ ions in the sequestered
      domains to equilibrate with the lumen, and energy coupling showed delocalized
      characteristics. The existence of such a gating function implies that a closed
      gate configuration would block lumenal H+ ions from entering the CF0-CF1 complex.
      In this work that prediction was tested using as an assay the dark, acid-base
      jump ATP formation phenomenon driven by H+ ions derived from succinic acid loaded
      into the lumen. Chlorpromazine, a photoaffinity probe for many proteins having
      high-affinity Ca(++)-binding sites, covalently binds to the 8-kDa CF0 subunit in
      the largest amounts when there is sufficient Ca++ to favor the localized energy
      coupling mode, i.e., the "gate closed" configuration. Photoaffinity-bound
      chlorpromazine blocked 50% or more of the succinate-dependent acid-base jump ATP
      formation, provided that the ionic conditions during the UV photoaffinity
      treatment were those which favor a localized energy coupling pattern and a higher
      level of chlorpromazine labeling of the 8-kDa CF0 subunit. Thylakoids held under
      conditions favoring a delocalized energy coupling mode and less chlorpromazine
      labeling of the CF0 subunit did not show any inhibition of acid-base jump ATP
      formation. Chlorpromazine and calmidazolium, another Ca(++)-binding site probe,
      were also shown to block redox-derived H+ initially released into sequestered
      domains from entering the lumen, at low levels of domain H+ accumulation, but not
      at higher H+ uptake levels; ie., the closed gate state can be overcome by
      sufficiently acidic conditions. That is consistent with the observation that the
      inhibition of lumenal succinate-dependent ATP formation by photoaffinity-attached
      chlorpromazine can be reversed by lowering the pH of the acid stage from 5.5 to
      4.5. The evidence is consistent with the concept that Ca++ bound at the lumenal
      side of the CF0 H+ channel can block H+ flux from either direction, consistent
      with the existence of a molecular structure in the CF0 complex having the
      properties of a gate for H+ flux across the inner boundary of the CF0. Such a
      gate could control the expression of localized or delocalized delta approximately
      mu H+ energy coupling gradients.

PMID- 8132496
TI  - Yeast mitochondrial calcium uptake: regulation by polyamines and magnesium ions.
AB  - Spermine, spermidine, and magnesium ions modulate the kinetic parameters of the
      Ca2+ transport system of Endomyces magnusii mitochondria. Mg2+ at concentrations
      up to 5 mM partially inhibits Ca2+ transport with a half-maximal inhibiting
      concentration of approximately 0.5 mM. In the presence of 2 mM MgCl2, the S0.5
      value of the Ca2+ transport system increases from 220 to 490 microM, which
      indicates decreased affinity for the system. Spermine and spermidine exert an
      activating effect, having half-maximal concentrations of 12 and 50 microM,
      respectively. In the case of spermine, the S0.5 value falls to 50-65 microM,
      which implies an increase in the transport system affinity for Ca2+. Both Mg2+
      and spermine cause a decrease of the Hill coefficient, giving evidence for a
      smaller degree of cooperativity. Spermine and spermidine enable yeast
      mitochondria to remove Ca2+ from the media completely. In contrast, Mg2+ lowers
      the mitochondrial buffer capacity. When both Mg2+ and spermine are present in the
      medium, their effects on the S0.5 value and the free extramitochondrial Ca2+
      concentration are additive. The ability of spermine and Mg2+ to regulate yeast
      mitochondrial Ca2+ transport is discussed.

PMID- 8132497
TI  - Expression of the Duffy antigen in K562 cells. Evidence that it is the human
      erythrocyte chemokine receptor.
AB  - The human malarial parasite Plasmodium vivax invades erythrocytes by binding to a
      cell surface protein identified as the Duffy blood group antigen. The molecular
      properties of the Duffy antigen, which was recently cloned, are very similar to
      those of a chemokine binding protein known as the human erythrocyte chemokine
      receptor. This has led to the suggestion that these two molecules are the same
      protein. To further investigate the suspected double identity of the Duffy
      antigen we have transfected it into a human erythroleukemic cell line, K562.
      Cells stably expressing the Duffy antigen were isolated and used to characterize
      the protein. K562 cells transfected with the Duffy antigen displayed specific
      125I-melanoma growth-stimulating activity (MGSA) binding while mock transfected
      cells did not. Comparison of 125I-MGSA binding to the Duffy antigen and the human
      erythrocyte chemokine receptor showed that the specific 125I-MGSA binding to both
      proteins was displaced by excess unlabeled MGSA, interleukin-8, RANTES, monocyte
      chemotactic peptide-1, and platelet factor 4, but not by macrophage inflammatory
      protein-1 alpha or -1 beta. Scatchard analysis of competition binding studies
      with these unlabeled chemokines revealed high affinity binding to the Duffy
      antigen with KD binding values of 24 +/- 4.9, 20 +/- 4.7, 41.9 +/- 12.8, and 33.9
      +/- 7 nM for MGSA, interleukin-8, RANTES, and monocyte chemotactic peptide-1,
      respectively. A monoclonal antibody, Fy6, to the Duffy antigen inhibited 125I
      MGSA binding to K562 cells expressing the Duffy antigen. Cell membranes from K562
      cells permanently expressing the Duffy antigen were chemically cross-linked with
      125I-MGSA. SDS-polyacrylamide gel electrophoresis analysis of the cross-linked
      products showed covalent incorporation of radiolabeled MGSA into a protein of
      molecular mass 47 kDa, and cross-linking was inhibited in the presence of
      unlabeled MGSA. These studies provide evidence that the Duffy blood group antigen
      is the same protein as the human erythrocyte chemokine receptor.

PMID- 8132498
TI  - Differential regulation by cAMP-dependent protein kinase and protein kinase C of
      the mu opioid receptor coupling to a G protein-activated K+ channel.
AB  - A mu opioid receptor and a G protein-activated K+ channel were coexpressed in
      Xenopus oocytes. Stimulation of the mu opioid receptor induced an inwardly
      rectifying current that was blocked by opioid receptor antagonist naloxone,
      indicating that the mu opioid receptor is functionally coupled to the K+ channel.
      The coupling is mediated by G proteins, since pertussis toxin treatment reduced
      the K+ current and injection of GTP gamma S (guanosine 5'-O-(thiotriphosphate))
      enhanced it. Repeated stimulation of the mu receptor leads to desensitization, as
      the K+ current from the second stimulation was reduced to 70% of that from the
      first one. Both cAMP-dependent protein kinase (PKA) and protein kinase C (PKC)
      regulate this process, but in opposite direction. Activation of PKC by treatment
      of the oocyte with phorbol ester potentiated the desensitization of the mu
      receptor-induced current. However, incubation of the cell with a membrane
      permeable cAMP analog, 8-chlorophenylthio-cAMP, completely abolished the
      desensitization. The cAMP effect appears to be mediated by PKA, since injection
      of a PKA catalytic subunit showed the same effect as cAMP incubation. These
      results suggest that PKA and PKC differentially regulate the mu opioid receptor
      coupling to the G protein-activated K+ channel.

PMID- 8132499
TI  - The secA inhibitor, azide, reversibly blocks the translocation of a subset of
      proteins across the chloroplast thylakoid membrane.
AB  - The presence of secA and secY gene homologues in the plastid genomes of red algae
      and cyanophytes has raised the possibility that the products of these genes are
      involved in protein translocation across the thylakoid membrane. Bacterial SecA
      proteins are effectively inhibited by azide, and we have tested the effects of
      this compound on the transport of lumenal proteins across the thylakoid membrane
      in pea chloroplasts. Recent studies have shown that lumenal proteins are
      transported by two different mechanisms, one dependent on the thylakoidal delta
      pH and the other requiring the presence of a stromal protein factor and ATP. In
      this report we show that azide inhibits the transport across the thylakoid
      membrane of the latter group of proteins, which includes plastocyanin and the
      lumenal 33-kDa protein of photosystem II; translocation of proteins by the delta
      pH-dependent pathway is unaffected. Following import into isolated chloroplasts
      in the presence of azide, a substantial proportion of plastocyanin and the 33-kDa
      protein is found as the stromal intermediate form; the proportion increases with
      lower ATP concentrations, suggesting that azide and ATP may compete for a single
      site. The presence of azide completely inhibits the import of the 33-kDa protein
      by isolated thylakoids, but import is restored if the azide is removed from the
      stromal extract or thylakoids, prior to the import incubation. The data thus
      indicate that azide reversibly inhibits the transport of a subset of proteins
      across the thylakoid membrane, consistent with the involvement of a SecA homolog.
      The results also indicate that azide is potentially a valuable tool for the
      future assignment of novel lumenal proteins to one of the thylakoidal protein
      transport mechanisms.

PMID- 8132500
TI  - Nuclear phosphatidylinositols decrease during S-phase of the cell cycle in HeLa
      cells.
AB  - In the current study we have measured phosphatidylinositols during the cell
      cycle. HeLa cells were labeled with [3H]myoinositol to a steady state,
      synchronized to the G1/S boundary, and the levels of phosphatidylinositol
      (PtdIns) lipids were measured at various times after release from the block. The
      levels of total cellular PtdIns, PtdIns(4)P, and PtdIns(4,5)P2 relative to total
      cellular phospholipid did not vary throughout the cell cycle. We then isolated
      nuclei from synchronized cells using a non-detergent method and found that the
      levels of nuclear PtdIns lipids decreased by over 50% at 2 and 4 h after release
      from the G1/S boundary (S-phase of the cell cycle) and returned to the original
      levels by 9 h. Separation of individual inositol-containing nuclear lipids showed
      that PtdIns decreased by 50% while levels of PtdIns(4)P and PtdIns(4,5)P2
      decreased by 66%. Levels of the cytoplasmic PtdIns lipids remained constant
      throughout this period. This experiment indicates that there is specific nuclear.
      PtdIns turnover that is activated during DNA synthesis.

PMID- 8132501
TI  - cAMP and beta gamma subunits of heterotrimeric G proteins stimulate the mitogen
      activated protein kinase pathway in COS-7 cells.
AB  - Mitogen-activated protein kinases (MAPKs) are activated by a variety of
      extracellular stimuli, including agonists for G protein-coupled receptors. Using
      transient transfection of COS-7 cells, we have studied the stimulation of a
      hemagglutinin-tagged p44mapk (p44HA-mapk) by receptors coupled to Gs, Gq, and Gi.
      Agonists that act via all three G proteins stimulated p44HA-mapk activity. A
      constitutively activated alpha s mutant, forskolin, and a cAMP analog also
      increased p44HA-mapk activity, indicating that cAMP in COS-7 cells, in contrast
      to other cell types, activates the MAPK pathway. Similarly, a constitutively
      activated alpha q mutant, overexpression of phospholipase C-beta 2, and a phorbol
      ester also stimulated p44HA-mapk, suggesting that Gq-coupled receptors stimulate
      the MAPK pathway by increasing phosphatidylinositol turnover and probably
      stimulating protein kinase C. In COS-7 cells, in contrast to Rat-1 cells,
      mutationally activated alpha i did not stimulate the MAPK pathway. G protein beta
      and gamma subunits, overexpressed together, did activate p44HA-mapk; this finding
      suggests that in COS-7 cells Gi-coupled receptors may stimulate the MAPK pathway
      through beta gamma. These unexpected results in COS-7 cells show that G proteins
      and second messengers regulate the MAPK pathway differently in different cell
      types.

PMID- 8132502
TI  - Molecular cloning and chemical synthesis of a novel antibacterial peptide derived
      from pig myeloid cells.
AB  - A group of myeloid precursors of defense peptides has recently been shown to have
      highly homologous N-terminal regions. Using a strategy based on this homology, a
      novel cDNA was cloned from pig bone marrow RNA and found to encode a 153-residue
      polypeptide. This comprises a highly conserved region encompassing a 29-residue
      signal peptide and a 101-residue prosequence, followed by a unique, 23-residue,
      cationic, C-terminal sequence. A peptide corresponding to this C-terminal
      sequence was chemically synthesized and shown to exert antimicrobial activity
      against both Gram positive and negative bacteria at concentrations of 2-16
      microM. The activity of this potent and structurally novel antibacterial peptide
      appears to be mediated by its ability to damage bacterial membranes, as shown by
      the rapid permeabilization of the inner membrane of Escherichia coli.

PMID- 8132503
TI  - Cloning and characterization of chloroplast and cytosolic forms of cyclophilin
      from Arabidopsis thaliana.
AB  - Cyclophilin (CyP), a protein with peptidyl-prolyl cis-trans isomerase (rotamase)
      activity, is the specific cellular target of cyclosporin A. We have isolated cDNA
      clones of two genes (designated ROC1 and ROC4) encoding CyP homologs from
      Arabidopsis thaliana (L.). The protein products of these genes are distinct from
      a previously identified Arabidopsis CyP. ROC1 is expressed in all tested plant
      organs and encodes a protein which is highly similar to previously described
      cytosolic CyP isoforms of other plants. In contrast, ROC4 is expressed only in
      photosynthetic organs and encodes a protein which includes an amino-terminal
      extension with properties of known chloroplast transit peptides. In vitro import
      experiments using the putative precursor protein to ROC4 showed that the protein
      is imported into chloroplasts where it is processed to the predicted mature size.
      Rotamase assays and immunoblot analysis of subcellular fractions indicate the
      presence of a CyP isoform in the stroma of chloroplasts but not in the thylakoid
      membranes or thylakoid lumen. Together, these data show that ROC4 is a novel CyP
      isoform which is located in the stroma of chloroplasts. In vitro chloroplast
      import of precursors of other chloroplast proteins was unaffected by
      concentrations of cyclosporin A which completely inhibit rotamase activity of
      chloroplast stromal CyP. Thus, this activity is not essential for protein import
      into chloroplasts.

PMID- 8132504
TI  - Differential estrogenic regulation of small M(r) heat shock protein expression in
      osteoblasts.
AB  - Polymerase chain reaction amplification and sequencing of heat shock protein
      (HSP) 27-related transcripts present in cDNAs generated from heat-shocked
      osteoblast RNA revealed the expression of three related open reading frames that
      encode proteins of 208, 197, or 175 amino acids. Their expression as recombinant
      proteins in Escherichia coli demonstrated that they encode 27,000, 25,000, or
      22,000 M(r) proteins. Northern blot analysis of heat shock protein 27-related
      transcript expression revealed that, while HSP 27 expression (850-nucleotide
      transcript) was induced by heat shock alone, the expression of a smaller
      transcript was facilitated by estrogen treatment prior to heat shock. This
      corresponded with the co-induction of 18,000 and 22,000 M(r) proteins by estrogen
      pretreated, heat-shocked osteoblasts as revealed by fluorography. The
      identification of these multiple small M(r) heat shock-induced proteins
      demonstrated that the stress response of mammalian cells is composed of multiple,
      related proteins whose expression is differentially regulated. The importance of
      estrogen-regulation of the small M(r) heat shock protein component of the stress
      response may be of particular significance to osteoblast physiology.

PMID- 8132505
TI  - Glycogenesis from glucose and ureagenesis in isolated perfused rat livers.
      Influence of ammonium ion, norvaline, and ethoxyzolamide.
AB  - The probable involvement of hepatic carbamyl-P in the reciprocal relationship
      between hepatic ureagenesis and glycogenesis from glucose was explored. Isolated
      perfused liver preparations from 48-h fasted rats were employed. Moderate (9.2
      mM) and relatively high levels of glucose (34 mM) were perfused. Hepatic
      glycogenesis, glucose-6-P, carbamyl-P, and citrulline levels, hepatic urea
      formation, and ureagenesis based upon perfusate urea levels were measured.
      Experimental probes selected to modify hepatic ureagenesis and carbamyl-P
      production and utilization included: (a) NH4Cl, maintained at 5 mM by continuous
      infusion (NH4+ is a substrate for carbamyl-P synthase I and glutamate
      dehydrogenase); (b) norvaline, an inhibitor of ornithine transcarbamylase which
      catalyzes the first committed step in the urea cycle; and (c) ethoxyzolamide, an
      inhibitor of carbonic anhydrase which produces HCO3-, an essential substrate for
      carbamyl-P synthase I. NH4+ increased ureagenesis and decreased glycogenesis. The
      inclusion of norvaline with NH4+ decreased ureagenesis and increased
      glycogenesis. Ethoxyzolamide with or without NH4+ inhibited both ureagenesis and
      glycogenesis, and decreased the hepatic glucose-6-P level. Glycogenesis was
      greater at 34 mM than 9.2 mM glucose, increased in norvaline-containing
      preparations correlative with increased availability of carbamyl-P, and decreased
      when carbamyl-P formation was inhibited by ethoxyzolamide. Kinetic analysis
      indicated a Km, Glc of 31 mM for glucose phosphorylation preliminary to
      glycogenesis. Glycogen formation via the "indirect pathway" (i.e. involving
      extrahepatic glycolysis, transport of lactate to the liver, and glyconeogenesis
      therefrom) was quantitatively insufficient to account for the observed
      glycogenesis. Glucokinase is contraindicated by the inverse relationship between
      hepatic glycogenesis and ATP availability in the ethoxyzolamide-treated
      preparations. In contrast, carbamyl-P:glucose phosphotransferase activity of the
      glucose-6-phosphatase system has the characteristics to bridge hepatic
      ureagenesis and glycogenesis.

PMID- 8132506
TI  - Evidence that an archaeal alpha-like DNA polymerase has a modular organization of
      its associated catalytic activities.
AB  - In this study we report on the evidence that an alpha-like DNA polymerase
      purified from the thermoacidophilic archaeon Sulfolobus solfataricus has a
      modular organization of its associated catalytic activities (polymerase and 3'-5'
      exonuclease). This enzyme, a monomer of about 100 kDa whose complete primary
      structure is available, has a protease hypersensitive site that is likely to be
      cleaved by the action of endogenous proteases during the purification procedure.
      As a consequence of that, two proteolytic fragments of about 50 and 40 kDa, in
      addition to the intact 100-kDa molecular species, can be detected upon SDS-PAGE
      of highly purified S. solfataricus DNA polymerase samples. The amino-terminal
      microsequence analysis by Edman degradation has revealed that the 50- and the 40
      kDa polypeptides correspond to the carboxyl- and the amino-terminal portion of
      the protein molecule, respectively. Using the bidimensional activity gel assay
      procedure, recently described by Longley and Mosbaugh (Longley, M. J., and
      Mosbaugh, D. W. (1991) Biochemistry 30, 2655-2664), we have demonstrated that the
      50-kDa fragment retains a Mg(2+)-dependent DNA polymerizing activity, whereas the
      40-kDa polypeptide is able to catalyze the excision of mispaired nucleotides at
      the 3'-OH terminus of a primer/template DNA substrate in the presence of Mn2+
      ions. On the other hand, the 100-kDa protein possess both activities. To date,
      this is the first report indicating, on the basis of direct functional data, that
      the polymerization and the 3'-5' exonuclease activity of a family B DNA
      polymerase can be ascribed to physically distinct modules of the enzyme molecule.

PMID- 8132507
TI  - Effects of DNA methylation on topoisomerase I and II cleavage activities.
AB  - DNA methylation is deregulated during oncogenesis. Since several major anti
      cancer drugs act on topoisomerases, we investigated the effects of cytosine
      methylation on topoisomerase cleavage activities. Both topoisomerase I and II
      cleavage patterns were modified by CpG methylation in c-myc gene DNA fragments.
      Topoisomerase II changes, mainly cleavage reduction, occurred for methylation
      sites within 7 base pairs from the topoisomerase II breaks and were different for
      VM-26 and azatoxin. For topoisomerase I, cleavage enhancement as well as
      suppression were observed. Using synthetic methylated oligonucleotides, we show
      that hemimethylation is sufficient to alter topoisomerase I activity. Cytosine
      methylation on the scissile strand within the topoisomerase I consensus sequence
      had strong effects. Cleavage was stimulated by methylation at position -4 and was
      strongly inhibited by methylation at position -3 (with position -1 being the
      enzyme-linked nucleotide). This inhibitory effect was attributed to the presence
      of a methyl group in the major groove, since the transition uracil to thymine
      also inhibited cleavage. Altogether these results suggest an interaction of
      topoisomerase I with the DNA major grove at positions -3 and -4. In addition, DNA
      methylation may have profound effects on the activity of topoisomerases and may
      alter the distribution of cleavage sites produced by anticancer drugs in
      chromatin.

PMID- 8132508
TI  - Expression of mammalian S-adenosylmethionine decarboxylase in Escherichia coli.
      Determination of sites for putrescine activation of activity and processing.
AB  - Mammalian S-adenosylmethionine decarboxylase (AdoMetDC) is known to be regulated
      by putrescine in two ways: (a) acceleration of the rate of conversion of the
      proenzyme into the mature enzyme in a reaction that forms the pyruvate prosthetic
      group and (b) activation of the mature enzyme activity. To determine sites of
      putrescine interaction with AdoMetDC, putrescine stimulation of both proenzyme
      processing and catalytic activity was tested with mutant AdoMetDCs in which
      specific amino acid residues, conserved between mammalian and yeast AdoMetDCs,
      had been altered by site-directed mutagenesis. Mutations E178Q or E256Q (and the
      previously reported mutation E11Q (Stanley, B. A., and Pegg, A. E. (1991) J.
      Biol. Chem. 266, 18502-18506)) abolished stimulation by putrescine without an
      effect on the processing rate in the absence of putrescine. Mutations E11K, as
      well as Y112A and L259Stop, completely abolished processing regardless of
      putrescine concentration, whereas mutation E133Q conferred an absolute putrescine
      requirement for processing to occur. Mutation E132Q, E135Q, E183Q, or D185N had
      no effect on proenzyme processing. The effects of mutations on enzyme activity
      were determined using AdoMetDC protein produced in Escherichia coli and purified
      by affinity chromatography. Mutation E11Q completely inactivated the enzyme,
      mutation E133Q reduced the catalytic constant by > 10(4), and mutation E256Q
      produced a 20-fold decrease. Putrescine did not stimulate the activity of mutants
      E178Q and E256Q but did activate mutants E133Q and E183Q. It is concluded that
      residues Glu-11, Glu-178, and Glu-256 are critical residues in the putrescine
      stimulation of AdoMetDC proenzyme processing and that Glu-178 and Glu-256 are
      critical for putrescine stimulation of AdoMetDC catalytic activity.

PMID- 8132509
TI  - Mutation of cysteine 254 facilitates the conformational changes accompanying the
      interconversion of persulfide-substituted and persulfide-free rhodanese.
AB  - Mutants of rhodanese (EC 2.8.1.1) that substitute Ser for Cys-254 and/or Cys-263,
      i.e. C254S, C263S, and the double mutant C254/263S, were compared with the wild
      type enzyme to test the hypothesis that the persulfide formation to give sulfur
      substituted rhodanese (ES) during catalysis can exert a stabilizing influence on
      the global structure of the protein. All the ES forms were quite refractory
      toward limited tryptic digestion. Extensive digestion was observed only in the
      persulfide-free forms (E) of mutants having substitutions of Ser for Cys-254
      (C254/263S and C254S). Limited proteolysis of C254/263S produced a species on SDS
      gels at approximately 21 kDa that was proteolyzed further to give a slightly
      smaller product. Amino acid sequencing, together with mass spectrometry,
      indicated that these two components had the same N-terminal sequence as wild-type
      rhodanese and that they resulted from cleavage in the C-terminal domain, first at
      residues Arg-186 or Arg-182 and subsequently at Arg-175 or Lys-174. In addition
      to increased proteolytic susceptibility, the conversion from ES to E of C254/263S
      was accompanied by increased hydrophobic exposure and increased quenching of the
      intrinsic protein fluorescence by acrylamide. The substitution of Ser for Cys
      254, within the helix suggested to be involved in stabilizing the persulfide bond
      in ES, seems to promote the formation of flexible conformations of sulfur-free
      rhodanese. In keeping with this model, C254/263S shows a marked increase in the
      hysteresis that is observed in rhodanese catalysis at pH 7 and high ionic
      strength. These results can be understood in terms of a model, suggesting that
      there is mutual stabilization of the protein structure and the persulfide bond in
      the ES form of rhodanese.

PMID- 8132510
TI  - The hormone-binding role of 2 cysteines near the C terminus of the mouse
      glucocorticoid receptor.
AB  - Previous biochemical analyses with covalent affinity labels and thiol-blocking
      reagents suggested possible roles for one methionine residue and multiple
      cysteine residues in binding of steroid to the 250-amino acid hormone-binding
      domain at the C-terminal end of mammalian glucocorticoid receptors. To test the
      functional roles of these residues in the receptor's ability to bind hormone and
      active transcription of target genes, the mouse glucocorticoid receptor cDNA was
      specifically mutated to cause single amino acid substitutions for methionine 610
      and for each of the 5 cysteines (at positions 628, 644, 649, 671, and 742) in the
      hormone-binding domain. Among these 6 residues, only mutations in cysteine 671
      and cysteine 742 caused substantial reductions in function. In transient
      transfection assays, the concentration of dexamethasone required for half-maximal
      activation of a glucocorticoid-responsive reporter gene was increased by 10-40
      fold by changing cysteine 742 to serine or cysteine 671 to serine or alanine. At
      saturating concentrations of dexamethasone, the mutant receptors activated the
      reporter gene to the same extent as the wild type receptor, indicating that the
      mutations affected only the hormone-binding function of the receptor and not its
      ability to bind DNA or activate transcription once the hormone was bound.

PMID- 8132511
TI  - Introduction of a tryptophan reporter group into loop 1 of the recA protein.
      Examination of the conformational states of the recA-ssDNA complex by
      fluorescence spectroscopy.
AB  - Site-directed mutagenesis was used to replace His-163 in the Loop 1 region of the
      recA protein with a tryptophan residue. The [H163W]recA protein binds single
      stranded DNA (ssDNA), catalyzes ssDNA-dependent ATP hydrolysis, and is fully
      active in the three-strand exchange reaction. In addition, the fluorescence
      properties of the Trp-163 reporter group are very sensitive to the binding of
      nucleotide cofactors to the H163W]recA-ssDNA complex. The fluorescence of Trp-163
      is modestly quenched by the binding of ADP (21%) and strongly quenched by the
      nonhydrolyzable ATP analog, ATP gamma S (70%); since ADP and ATP gamma S
      stabilize the closed and open conformations of the recA-ssDNA complex,
      respectively, the quenched states observed with these nucleotides likely reflect
      differences in the fluorescence properties of tryptophan 163 in these two states.
      ATP has a more complex time-dependent effect on Trp-163 fluorescence. When ATP is
      added to [H163W]recA-ssDNA complexes, there is an immediate quenching of Trp-163
      fluorescence (44%) which is intermediate in intensity between that observed with
      ADP and ATP gamma S. The ATP-induced quenching gradually decreases with time as
      the pool of ATP is converted to ADP by the ATP hydrolysis activity of the
      [H163W]recA protein. These results are discussed with regard to the nucleotide
      cofactor-dependent conformational transitions of the recA-ssDNA complex.

PMID- 8132512
TI  - Insulin-sensitive association of GLUT-4 with endocytic clathrin-coated vesicles
      revealed with the use of brefeldin A.
AB  - The interaction of the adipocyte/skeletal muscle glucose transporter (GLUT-4)
      with clathrin lattices may be important in maintaining its intracellular
      distribution. To better understand the role of clathrin lattices in the sorting
      of GLUT-4, we have attempted to determine the cellular origin of clathrin-coated
      vesicles (CCVs) that contain this transporter. The fungal toxin brefeldin A (BFA)
      causes the selective disassembly of clathrin lattices at the trans-Golgi network
      (TGN), but not at the plasma membrane (PM), thus providing a way of estimating
      the proportion of GLUT-4 in PM- versus TGN-derived clathrin lattices. Exposure of
      3T3-L1 adipocytes to BFA resulted in a rapid disassembly of clathrin lattices at
      the TGN, observed by optical sectioning microscopy, and to a pronounced decrease
      in the yield of CCVs purified from these cells. Thus, CCVs isolated from BFA
      treated cells are likely to be derived from the PM. Immunoblotting experiments
      revealed the presence of GLUT-4 in such CCVs, suggesting that under basal
      conditions the transporter is continually retrieved from the PM through the CCV
      pathway. Exposure of both BFA-treated or non-treated cells to insulin resulted in
      a 4-6-fold increase in the concentration of GLUT-4 at the PM. In parallel, the
      concentration of GLUT-4 in PM-derived CCVs decreased by 60%. These results
      suggest (a) that the effect of insulin to increase the cell surface concentration
      of GLUT-4 is not inhibited by BFA, and (b) that a decreased association of GLUT-4
      with endocytic CCVs may be important in facilitating its increased cell surface
      concentration in response to the hormone.

PMID- 8132513
TI  - Conversion of an anti-single-stranded DNA active site to an anti-fluorescein
      active site through heavy chain complementarity determining region
      transplantation.
AB  - Complementarity determining region (CDR) transplant studies were conducted
      between two monoclonal antibodies of distinctly different specificities (anti
      fluorescein monoclonal antibody (mAb) 4-4-20 and anti-single-stranded DNA (ssDNA)
      mAb 04-01) which possessed nearly identical light chains but dissimilar heavy
      chains. The variations in binding specificities between the two immunoglobulins
      suggested that the active-site features of anti-fluorescein antibodies were
      dictated by characteristics intrinsic to the heavy chain (H-chain). To identify
      specific regions of the H-chain which influence the structure and function of an
      anti-fluorescein active site, CDR transplantation was systematically employed to
      convert the anti-ssDNA 04-01 antibody active site to an active site with anti
      fluorescein activity. Each mAb 4-4-20 H-chain CDR (HCDR) was transplanted into
      the H-chain of a single-chain derivative of the 04-01 molecule. A fluorescence
      polarization ligand binding assay was utilized to determine the equilibrium
      dissociation constant, Kd, of hybrid transplant single-chain antibody HCDR1-HCDR2
      HCDR3(4-4-20) for fluorescein (3.8 x 10(-7) M, indicating successful conversion
      of an anti-ssDNA active site to an anti-fluorescein binding site. A similar Kd
      (6.3 x 10(-7) M) was determined using a fluorescein fluorescence quenching assay.
      The transplantation results are discussed in terms of the relative contribution
      of each HCDR to a successful conversion in antibody specificity.

PMID- 8132514
TI  - Complex interactions at a GC-rich domain regulate cell type-dependent activity of
      the ornithine decarboxylase promoter.
AB  - Regulation of ornithine decarboxylase (ODC) is critical to the control of
      cellular growth, differentiation, and carcinogenesis. A GC-rich region in the ODC
      promoter contains two overlapping protein binding sites that interact to regulate
      basal level expression in some cell types. A perfect binding motif for
      transcription factor Sp1 (CCCCGCCCC) is located at nucleotides -114 to -106
      relative to the site of transcriptional initiation, binds strongly to purified
      Sp1 protein, and forms several complexes when incubated with nuclear extracts.
      Only one of these complexes is recognized by Sp1-specific antibody. A new protein
      binding motif (GCCCCTCCCC, located at -110 to -100) partially overlaps with the
      Sp1 site and analyses by DNase I protection showed that a new protein ("NF-ODC1")
      and the Sp1-like proteins interact with the ODC promoter in a mutually exclusive
      manner. Mutation of the NF-ODC1 binding motif strongly enhanced ODC promoter
      strength in some cell types, but had little or no influence in others. The effect
      of mutating the Sp1 site also varied with cell type. These cell type
      specificities did not correlate with the levels of Sp1 and NF-ODC1 binding
      activities in nuclear extracts. These results show that regulation of the ODC
      promoter by the Sp1 family is cell type-specific and modulated by a negative
      effector that we have termed NF-ODC1.

PMID- 8132515
TI  - Chlorination of taurine by myeloperoxidase. Kinetic evidence for an enzyme-bound
      intermediate.
AB  - The chlorination of taurine by the myeloperoxidase-H2O2-Cl- system was
      investigated under steady state conditions. By systematically varying the pH and
      the concentrations of H2O2,Cl-, and taurine such that chloride inhibition and the
      unwanted formation of inactive compound II intermediate are minimized, rate data
      were found to fit a mechanism involving an enzyme-bound chlorinating
      intermediate. The mechanism we propose is as follows. [formula: see text] The
      kinetic parameters determined at pH 4.7 are: k1 = (3.3 +/- 0.2) x 10(7) M-1 S-1,
      k2 = (2.8 +/- 1.2) x 10(6) M-1 S-1, and k3 = (4.4 +/- 0.2) x 10(5) M-1 S-1. The
      rate constant for compound I formation (k1) is of the same order of magnitude as
      the value (1.8 x 10(7) M-1 S-1) obtained using transient state techniques in a
      previous study by our group. The value of k3 is 2 orders of magnitude greater
      than the non-enzymatic reaction between HOCl and taurine at the same pH. The
      results of this study indicate that the chlorination reaction mediated by the
      myeloperoxidase system in vivo may involve an enzyme intermediate species rather
      than free HOCl. Not only does this mechanism offer the advantage of substrate
      specificity but also of speed compared to the non-enzymatic reaction. This
      mechanism can also explain how the indiscriminate oxidation reactions by HOCl are
      prevented in the leukocyte. The fast formation of taurine monochloramine, a
      relatively non-toxic and stable compound compared to HOCl, is consistent with the
      proposed role of taurine in the neutrophil, that of protecting certain targets
      including myeloperoxidase from the attack by potent chlorinated oxidants.

PMID- 8132517
TI  - A proteolytic fragment of Trypanosoma cruzi trans-sialidase lacking the carboxyl
      terminal domain is active, monomeric, and generates antibodies that inhibit
      enzymatic activity.
AB  - trans-Sialidase isolated from trypomastigote forms of Trypanosoma cruzi, the
      protozoan parasite that causes Chagas' disease, is multimeric and heterogeneous
      in size. We show here that limited proteolysis of tans-sialidase with papain
      yields a single monomeric polypeptide chain of 70 kDa that conserves full
      enzymatic activity on soluble and membrane-bound substrates. The papain fragment
      lacks most of the 12-amino acid repeats of the carboxyl-terminal domain that
      comprises about 50% of the native trans-sialidase. When injected into rabbits,
      the papain-generated fragment induces antibodies that inhibit trans-sialidase
      activity and trypomastigote sialylation. The repeats are also not required for
      the stability of the enzyme or for the correct folding during the biosynthesis in
      Escherichia coli, but seem essential for trans-sialidase oligomerization. We
      conclude that trans-sialidase is composed of two structurally and functionally
      independent domains.

PMID- 8132516
TI  - Muscarinic receptor activation down-regulates the type I inositol 1,4,5
      trisphosphate receptor by accelerating its degradation.
AB  - Stimulation of SH-SY5Y human neuroblastoma cells with carbachol, a muscarinic
      agonist, down-regulates the type I inositol 1,4,5-trisphosphate (InsP3) receptor
      by > 90% with maximal and half-maximal effects after approximately 6 h and
      approximately 1 h, respectively. Examination of the mechanistic basis of this
      down-regulation revealed that carbachol increased the rate of type I InsP3
      receptor degradation (radiolabeled immunoprecipitable receptor was lost from
      cells with half-times of > 8 h and approximately 1 h in the absence and presence
      of carbachol, respectively) and that the concentration of type I InsP3 receptor
      mRNA, despite a transient decrease after 3 h, did not correlate with levels of
      the receptor. Only those muscarinic receptor subtypes coupled to stimulation of
      phosphoinositide hydrolysis were capable of causing type I InsP3 receptor down
      regulation. Ca2+ mobilization was pivotal to the mechanisms of receptor down
      regulation, since perturbation of Ca2+ homeostasis with either EGTA or
      thapsigargin blocked the ability of carbachol to accelerate receptor degradation.
      Studies with thapsigargin also revealed that both functional InsP3-sensitive Ca2+
      stores and persistent elevation of InsP3 concentration were required for down
      regulation to occur. In conclusion, phosphoinositidase C-linked muscarinic
      receptors down-regulate the type I InsP3 receptor by accelerating its
      degradation. It appears that this process is initiated by persistent discharge of
      intracellular Ca2+ stores via the channels formed by tetramerically complexed
      type I InsP3 receptors.

PMID- 8132518
TI  - Lactate monooxygenase. I. Expression of the mycobacterial gene in Escherichia
      coli and site-directed mutagenesis of lysine 266.
AB  - Lactate monooxygenase utilizes oxygen in the conversion of L-lactate to acetate,
      CO2, and water. The gene for the enzyme from Mycobacterium smegmatis had been
      cloned into Escherichia coli (Giegel, D. A., Williams, C. H., Jr., and Massey, V.
      (1990) J. Biol. Chem. 265, 6626-6632) and the derived amino acid sequence
      compared to glycolate oxidase and flavocytochrome b2, enzymes of known three
      dimensional structure (Lindqvist, Y., and Branden, C. I. (1989) J. Biol. Chem.
      264, 3624-3628; Xia, Z. X., and Mathews, S. F. (1990) J. Mol. Biol. 212, 837
      863). There is strong homology, especially around residues in the active site.
      The mechanism proposed for lactate monooxygenase involves an intermediate having
      a negative charge at the N(1)-position of the FMN. Based on the homology, lysine
      266 is the residue suggested to neutralize that charge. Wild type enzyme and
      several forms of the enzyme altered at active site residues by site-directed
      mutagenesis have been expressed in E. coli and purification procedures developed.
      The properties determined for the recombinant wild type enzyme were, in every
      case, the same as those previously determined for the enzyme isolated from M.
      smegmatis. Mutation of lysine 266 to a methionine created K266M. The semiquinone
      showed spectral features different from those found in the wild type enzyme and
      was no longer thermodynamically stable. This indicates a redox potential for the
      enzyme-bound semiquinone/reduced flavin couple that is higher than the midpoint
      potential for the oxidized flavin/semiquinone couple. The two-electron redox
      potential was determined to be -180 mV at 25 degrees C, pH 7.0. In wild type
      enzyme, attack of the flavin ring by sulfite creates a negative charge at the FMN
      N(1)-position. In K266M, the stabilization of the sulfite adduct was 17,000-fold
      weaker (Kd approximately 10(-3) M) than in the wild type enzyme, with a rate of
      association that is lowered by 10,000-fold (kon = 1.2 M-1 s-1). The rate of
      reduction with L-lactate is significantly decreased in K266M. Unexpectedly,
      binding of substrate and inhibitors is significantly weaker in K266M than in the
      wild type enzyme. In all properties involving a negative charge at position N(1)
      of the FMN, K266M is distinctly different from wild type enzyme. This makes it
      quite likely that lysine 266 serves the postulated role of interacting with this
      negative charge.

PMID- 8132519
TI  - Lactate monooxygenase. II. Site-directed mutagenesis of the postulated active
      site base histidine 290.
AB  - Lactate monooxygenase catalyzes the oxidation of L-lactate with molecular oxygen
      to acetate, CO2, and water. Histidine 290 has been proposed to be the active site
      base in lactate monooxygenase (Giegel, D. A., Williams, C. H., Jr., and Massey,
      V. (1990) J. Biol. Chem. 265, 6626-6632) and was mutated to a glutamine (H290Q).
      The mutant enzyme shows properties that support strongly the postulated function
      of the histidine. The ability of L-lactate to reduce the enzyme flavin is
      essentially abolished, whereas reoxidation of reduced enzyme with oxygen proceeds
      at 1.4 x 10(4) M-1 s-1, a rate essentially like that found in the wild type
      enzyme. The substrate, L-lactate, is bound with a Kd equal to 2.0 x 10(-2) M, and
      D-lactate, a competitive inhibitor with a Kd of 3.1 x 10(-3) M. Both values are
      similar to binding measured in the wild type enzyme. Unlike the situation with
      wild type enzyme, where the transition state analog oxalate is bound tightly in a
      two-step reaction involving proton uptake from solution (Ghisla, S., and Massey,
      V. (1977) J. Biol. Chem. 252, 6729-6735), the mutant enzyme binds oxalate weakly,
      in a single step reaction, with a Kd in the order of 0.1 M. No effect was
      observed upon varying the pH, indicating that binding does not include a
      protonation step. Replacing the histidine also has a significant effect on the
      ability of the enzyme to stabilize the flavin N(5)-sulfite adduct. Sulfite is
      bound at least 1000-fold weaker than it is in the wild type enzyme.

PMID- 8132520
TI  - Lactate monooxygenase. III. Additive contributions of active site residues to
      catalytic efficiency and stabilization of an anionic transition state.
AB  - Lactate monooxygenase catalyzes the conversion of L-lactate to acetate, CO2, and
      water with incorporation of molecular oxygen. Several amino acid residues of
      lactate monooxygenase had been postulated to interact in specific ways with the
      bound substrate (Giegel, D. A., Williams, C. H., Jr., and Massey, V. (1990) J.
      Biol. Chem. 265, 6626-6632). Tyrosine 44 and arginine 293 were proposed to form a
      hydrogen bond and a salt bridge to the carboxyl-moiety of lactate. Tyrosine 152
      was suggested to form a hydrogen bond to the alpha-hydroxyl group and could be
      involved in stabilizing a transient carbanionic intermediate of the substrate.
      The tyrosine residues were replaced with phenylalanines (Y44F, Y152F), and
      arginine 293 was mutated to a lysine (R293K). In all cases catalysis was
      significantly decreased; however, the binding affinity for L-lactate did not
      decrease. Instead, the Kd measured for Y152F was 10-fold lower than that for the
      wild type enzyme. The products of turnover with Y152F were similar to those with
      wild type enzyme, with 70-80% of the reaction proceeding to form acetate, CO2,
      and H2O. The catalytic reactions with both Y44F and R293K were substantially
      uncoupled, with between 60 and 80% of the catalytic turnover forming pyruvate and
      H2O2. For all mutant forms the reoxidation of enzyme with oxygen in the absence
      of pyruvate occurred at a rate similar to that measured for the wild type enzyme.
      The most important effect of the mutations was in the ability to stabilize the
      transition state analog oxalate. A linear relationship was found between the rate
      of reduction of the enzyme flavin and the dissociation constant for the binding
      of oxalate, demonstrating that many individual residues contribute to the
      lowering of the energy of the transition state, in addition to specific functions
      being assignable to some specific residues.

PMID- 8132521
TI  - Interaction of NADPH-adrenoferredoxin reductase with NADP+ and adrenoferredoxin.
      Equilibrium and dynamic properties investigated by proton nuclear magnetic
      resonance.
AB  - NADPH-adrenoferredoxin reductase, a flavoprotein from bovine adrenocortical
      mitochondria, has been investigated to elucidate the equilibrium and dynamic
      properties of the interaction with NADP+ and adrenoferredoxin (adrenodoxin) using
      proton NMR spectroscopy. The line width of the signals from NADP+ depends on the
      presence of the reductase. The off rate constant of NADP+ from the reductase is
      estimated to be about 15-20 s-1 on the basis of line width measurements. No
      appreciable difference in off rate is detected between adenine and nicotinamide
      moieties of NADP+. Transferred nuclear Overhauser effect experiments for NADP+
      indicate the time-dependent magnetization transfer profiles with a long lag
      phase. The proton NMR spectra during the titration of the reductase with
      adrenodoxin reveal that the reductase possesses distinct binding sites for both
      NADP+ and adrenodoxin. The sharp resonances in the aromatic region due to His-10
      and His-62 of adrenodoxin were utilized as a probe to explore the interaction
      with the reductase. IN the mixture of adrenodoxin and the reductase at the mol
      ratio of 6:1, T1 values of the histidine residue in adrenodoxin were measured by
      the inversion recovery method. At low ionic strength, T1 values of the resonances
      are not affected in the presence or absence of the reductase. In the presence of
      the reductase, T1 values of resonances resulting from the histidine residues
      become shorter as the concentration of KCl increases because of rapid exchange
      between bound and free states. At low ionic strength (10 mM phosphate buffer),
      the off rate from the reductase is estimated to be less than about 4 s-1. The off
      rate of adrenodoxin from the reductase could be the rate-limiting step in
      cytochrome c reductase activity at low ionic strength.

PMID- 8132522
TI  - Roles of the membrane-interactive regions of factor VIIa and tissue factor. The
      factor VIIa Gla domain is dispensable for binding to tissue factor but important
      for activation of factor X.
AB  - The roles of the putative membrane-interactive regions of factor VIIa (fVIIa) and
      tissue factor (TF) have been examined. Enzymatic removal of the 4-carboxyglutamic
      acid (Gla) domain of fVIIa had no effect on hydrolysis of a tripeptidyl
      chromogenic substrate in the absence or presence of TF. Additionally, Gla
      domainless fVIIa (GdVIIa) was similar to native fVIIa in activating factor X in
      the absence of TF and phospholipid. However, GdVIIa in complex with recombinant
      soluble TF (sTF) was 76-fold less efficient in factor X activation than was
      fVIIa.sTF. The difference increased to 740-fold using TF relipidated in vesicles
      composed of 80% phosphatidylcholine and 20% phosphatidylserine (TF/PCPS). While
      Gla domain deletion produced a 10(3)-fold increase in the Kd for binding to
      TF/PCPS, the Kd for binding to TF/PC increased only 20-fold, and that for sTF in
      the absence of phospholipid increased 10-fold. Kd values for GdVIIa binding to
      TF/PCPS, TF/PC, or sTF were nearly identical. Thus, most of the binding energy
      required for formation of the fVIIa.TF complex was present even after Gla domain
      deletion. Both fVIIa and GdVIIa were capable of binding sTF in the presence of
      excess divalent metal-ion chelator, suggesting Ca(2+)-independent binding or the
      presence of a novel very high affinity Ca2+ binding site in fVIIa. The results
      demonstrate that the effect of the Gla domain on the Kd is apparent only in the
      presence of PS, and that interactions involving the fVIIa Gla domain and
      phospholipid are critical for efficient proteolysis of factor X on a membrane
      surface.

PMID- 8132523
TI  - Novel malonamidases in Bradyrhizobium japonicum. Purification, characterization,
      and immunological comparison.
AB  - Three novel malonamidases (E1a, E1b, and E2) occurring constitutively in
      Bradyrhizobium japonicum were purified to electrophoretic homogeneity. They were
      found to catalyze one or more of the following three types of reactions: malonyl
      transfer to hydroxylamine (reaction 1), hydroxaminolysis of malonamate (reaction
      2), and hydrolysis of malonamate (reaction 3). The molecular sizes of E1a, E1b,
      and E2 were 126, 107, and 103 kDa, respectively, and they were each composed of
      two identical subunits. The pIs of E1a and E1b, 5.5 and 5.0 respectively, were
      similar, but that of E2 was 7.2. Optimum pH values varied with the type of
      reactions catalyzed, but among the enzymes they were found to be similar. The
      affinity of E2 for malonamate was about 30- and 70-fold higher than that of E1a
      and E1b, respectively. Acetate and propionate inhibited E1a activity
      competitively, whereas malonate inhibited E2 activity noncompetitively. The amino
      acid composition and N-terminal amino acid sequence of the three enzymes were
      found to be different. These enzymes were also immunologically different. E1a was
      found to form a malonyl-enzyme intermediate during the catalysis through the
      isolation of [14C]malonyl-enzyme with gel filtration and through isotope exchange
      experiments with [18O]malonate. These malonamidases may play a role for the self
      protection against malonate toxicity in nodule bacteroids and may also be
      involved in the transport of fixed nitrogen to the plant cell.

PMID- 8132524
TI  - Interactions of cyclic hydrocarbons with biological membranes.
AB  - Many cyclic hydrocarbons, e.g. aromatics, cycloalkanes, and terpenes, are toxic
      to microorganisms. The primary site of the toxic action is probably the
      cytoplasmic membrane, but the mechanism of the toxicity is still poorly
      understood. The effects of cyclic hydrocarbons were studied in liposomes prepared
      from Escherichia coli phospholipids. The membrane-buffer partition coefficients
      of the cyclic hydrocarbons revealed that these lipophilic compounds
      preferentially reside in the membrane. The partition coefficients closely
      correlated with the partition coefficients of these compounds in a standard
      octanol-water system. The accumulation of hydrocarbon molecules resulted in
      swelling of the membrane bilayer, as assessed by the release of fluorescence self
      quenching of fluorescent fatty acid and phospholipid analogs. Parallel to the
      expansion of the membrane, an increase in membrane fluidity was observed. These
      effects on the integrity of the membrane caused an increased passive flux of
      protons and carboxyfluorescein. In cytochrome c oxidase containing
      proteoliposomes, both components of the proton motive force, the pH gradient and
      the electrical potential, were dissipated with increasing concentrations of
      cyclic hydrocarbons. The dissipating effect was primarily the result of an
      increased permeability of the membrane for protons (ions). At higher
      concentrations, cytochrome c oxidase was also inactivated. The effective
      concentrations of the different cyclic hydrocarbons correlated with their
      partition coefficients between the membrane and aqueous phase. The impairment of
      microbial activity by the cyclic hydrocarbons most likely results from
      hydrophobic interaction with the membrane, which affects the functioning of the
      membrane and membrane-embedded proteins.

PMID- 8132525
TI  - Tn10/IS10 transposase purification, activation, and in vitro reaction.
AB  - We describe a method for the purification of Tn10/IS10 transposase that relies on
      the aggregation of the protein after overexpression in Escherichia coli.
      Aggregated transposase was solubilized before the final purification step, a gel
      filtration column, using a combination of salt and detergent. This procedure is
      the first reported for the preparation of concentrated and active transposase
      from any IS element. The yield is 11 mg of purified protein at a concentration of
      1 mg/ml from 2.5 g of cells. The procedure can be scaled up with ease. We also
      describe a treatment that activates transposase in either a crude or purified
      state. This involves dilution into a solution of salt plus organic solvent. In
      transposition reactions using supercoiled substrate plasmid, the activity was
      directly proportional to the amount of transposase added over a wide range of
      transposase/DNA ratios (0.2-2.0 molecules/DNA substrate molecule). In this range
      8 transposase molecules were added per transposition event. Maximum conversion of
      substrate to product (40%) was with 18 transposase molecules/transposition event.
      At higher levels of transposase with a constant amount of substrate, activity was
      reduced but could be restored by addition of nonspecific DNA. Both the specific
      activity of transposase and the type of products generated can be altered by
      changing in vitro assay conditions. The effects of salts, solvents, and pH value
      on the reaction are described.

PMID- 8132526
TI  - Mechanism of cytostatic action of novel 5-(thien-2-yl)- and 5-(furan-2-yl)
      substituted pyrimidine nucleoside analogues against tumor cells transfected by
      the thymidine kinase gene of herpes simplex virus.
AB  - Several novel 5-substituted 2'-deoxyuridine (dUrd) analogues were evaluated as
      substrates for highly purified herpes simplex virus type 1 (HSV-1)-encoded
      thymidine kinase (TK) derived from HSV-1 TK gene-transfected murine mammary
      carcinoma FM3A cells, and human platelet thymidine (dThd) phosphorylase. The Ki
      of 5-(furan-2-yl)-dUrd, 5-(thien-2-yl)-dUrd and 5-(thien-2-yl)-dCyd for HSV-1 TK
      was 0.94, 0.71, and 1.32 microM, respectively. Inhibition was competitive with
      respect to the natural substrate dThd. With dCyd as substrate, the Ki of 5-(thien
      2-yl)-dCyd for HSV-1 TK was 4.5 microM (Ki/Km = 0.17). In striking contrast with
      (E)-5-(2-bromovinyl)-dUrd, the 5-(thien-2-yl)- and 5-(furan-2-yl)-dUrd
      derivatives were not substrates for human dThd phosphorylase. 5-(Thien-2-yl)
      dUrd, 5-(furan-2-yl)-dUrd and 5-(thien-2-yl)-dCyd were at least 100-fold more
      cytostatic to the HSV TK gene-transfected FM3A tumor cells than wild-type FM3A/0
      cells. The viral TK expressed in the HSV-1 TK gene-transfected tumor cells merely
      acts as an activating enzyme, whereas thymidylate synthase serves as the target
      enzyme for the cytostatic action of the compounds. The novel 5-substituted dUrd
      analogues should be further pursued as candidate drugs in the treatment of HSV TK
      gene-transfected tumors.

PMID- 8132527
TI  - Apolipoprotein A-I metabolism in cholesteryl ester transfer protein transgenic
      mice. Insights into the mechanisms responsible for low plasma high density
      lipoprotein levels.
AB  - Expression of simian cholesteryl ester transfer protein (CETP) in C57BL/6 mice
      causes the animals' high density lipoprotein (HDL) levels to decrease. The
      purpose of these studies was to determine how CETP expression caused that
      reduction. Chemical analysis showed that the HDL of the CETP transgenic mice had
      about twice as much triglyceride and only about 60% as much cholesteryl ester as
      the HDL from the C57BL/6 mice. Both strains of mouse had high levels of a
      circulating lipase. When plasma from the mice was incubated at 37 degrees C for 5
      h, the triglycerides in the HDL were hydrolyzed, and apoA-I was shed from the
      particle. However, apoA-I was shed from the CETP HDL more rapidly than it was
      shed from the C57BL/6 HDL. Because "free" apoA-I is rapidly cleared by the
      kidney, increased production of free apoA-I would be expected to shorten the
      average life span of apoA-I in the mouse. Kinetic analyses indicated that the
      life span of apoA-I was significantly reduced in the CETP transgenic mice. It was
      concluded that CETP expression enriched the core of the HDL with triglyceride,
      which rendered it vulnerable to lipolysis, causing apoA-I to be shed from the
      particle. That shortened the life span of apoA-I in the CETP mice, which led to
      lower plasma levels of the protein.

PMID- 8132528
TI  - Thiol/disulfide formation associated with the redox activity of the [Fe3S4]
      cluster of Desulfovibrio gigas ferredoxin II. 1H NMR and Mossbauer spectroscopic
      study.
AB  - Desulfovibrio gigas ferredoxin II (FdII) is a small protein (alpha 4 subunit
      structure as isolated; M(r) approximately 6400 per subunit; 6 cysteine residues)
      containing one Fe3S4 cluster per alpha-subunit. The x-ray structure of FdII has
      revealed a disulfide bridge formed by Cys-18 and Cys-42 approximately 13 A away
      from the center of the cluster; moreover, the x-ray structure indicates that Cys
      11 forms a disulfide bridge with a methanethiol. In the oxidized state, FdIIoxm
      the 1H NMR spectra, exhibit four low-field contact-shifted resonances at 29, 24,
      18, and 15.5 ppm whereas the reduced state, FdIIR (S = 2), yields two features at
      +18.5 and -11 ppm. In the course of studying the redox behavior of FdII, we have
      discovered a stable intermediate, FdIIint, that yields 1H resonances at 24, 21.5,
      21, and 14 ppm. This intermediate appears in the potential range where the
      cluster (E'0 approximately -130 mV) is reduced from the [Fe3S4]1+ to the [Fe3S4]0
      state. FdIIint is observed during reductive titrations with dithionite or
      hydrogen/hydrogenase or after partial oxidation of FdIIR by 2,6
      dichlorophenolindophenol or air. Our studies show that a total of three electrons
      per alpha-subunit are transferred to FdII. Our experiments demonstrate the
      absence of a methanethiol-Cys-11 linkage in our preparations, and we propose that
      two of the three electrons are used for the reduction of the disulfide bridge.
      Mossbauer (and EPR) studies show that the Fe3S4 cluster of FdIIint is at the same
      oxidation level as FdIIox, but indicate some changes in the exchange couplings
      among the three ferric sites. Our data suggest that the differences in the NMR
      and Mossbauer spectra of FdIIox and FdIIint result from conformational changes
      attending the breaking or formation of the disulfide bridge. The present study
      suggests that experiments be undertaken to explore an in vivo redox function for
      the disulfide bridge.

PMID- 8132529
TI  - Genetic evidence for activation of the positive transcriptional regulator Xy1R, a
      member of the NtrC family of regulators, by effector binding.
AB  - The Xy1R protein positively controls expression from the Pseudomonas putida TOL
      plasmid sigma 54-dependent Pu and Ps promoters, in response to the presence of
      aromatic effectors such as m-xylene, m-methylbenzyl alcohol, and p
      chlorobenzaldehyde in the culture medium. Xy1R also autoregulates its own
      synthesis. A mutant Xy1R regulator called Xy1R7 was isolated after
      nitrosoguanidine mutagenesis of the wild-type gene and phenotypic selection for
      mutants that had acquired the ability to recognize m-nitrotoluene, a nitroarene
      that is not an effector for the wild-type regulator. The mutant regulator
      exhibited a single point mutation that resulted in a change in codon 172 (GAA-
      >AAA), which should result in a Glu-->Lys change in the polypeptide chain. The
      effector profile of the mutant regulator was determined by measuring beta
      galactosidase from a fusion of the Pu promoter to a promoterless lacZ gene. The
      results showed that the mutant regulator had acquired the ability to recognize m
      nitrotoluene, and retained the wild-type regulator's ability to recognize most of
      the wild-type effectors. Full transcriptional activation of the Pu promoter by
      Xy1R7, as with the wild-type Xy1R protein, requires its full modular structure,
      namely the sigma 54 recognition site, the integration host factor binding site,
      and the upstream activation sequences. The Xy1R7 regulator did not stimulate
      transcription from the Ps promoter in response to the presence of its effectors,
      and autoregulated its own synthesis at low levels.

PMID- 8132530
TI  - Phospholipase D-mediated diradylglycerol formation coincides with H2O2 and
      lactoferrin release in adherent human neutrophils.
AB  - Polymorphonuclear leukocytes (PMNs) adherent to fibrinogen exhibit a delay in the
      onset of the respiratory burst in response to N-formyl-methionyl-leucyl
      phenylalanine (fMLP). Previously, we demonstrated that H2O2 release in adherent
      PMNs coincides with the exocytosis of lactoferrin-containing specific granules.
      Since diradylglycerol (DRG) has been implicated in PMN secretion and oxidant
      release, we measured DRG formation during PMN adhesion to fibrinogen. PMNs were
      added to fibrinogen-coated plastic in the presence of fMLP, and H2O2 release,
      lactoferrin release, and DRG formation measured over a time course of 120 min.
      H2O2 and lactoferrin release were not apparent until 45-60 min, reaching maximal
      levels by 120 min. In contrast, DRG concentration increased by 15-30 min, from
      275 +/- 27 pmol/mg of protein in resting cells to 600 +/- 173 pmol/mg protein in
      cells exposed to fMLP. DRG levels returned to base line by 30-45 min (383 +/- 32
      pmol/mg of protein) before increasing again between 60 and 120 min (944 +/- 230
      pmol/mg of protein and 1632 +/- 351 pmol/mg of protein, respectively).
      Propranolol, an inhibitor of phosphatidate phosphohydrolase, caused a dose
      dependent inhibition of both H2O2 and lactoferrin release, with maximal
      inhibition at 50-100 microM. Propranolol also inhibited the second, but not the
      first phase of DRG formation. Similarly, ethanol treatment completely blocked
      H2O2 and lactoferrin release, and the second phase of DRG formation. In the
      presence of ethanol, phospholipase D (PLD)-mediated formation of
      [3H]phosphatidylethanol from 3H-O-alkyl-phosphatidylcholine corresponded to the
      second, but not the first, phase of DRG formation (23,169 +/- 2,017 cpm/mg
      protein, ethanol versus 2,696 +/- 261 cpm/mg protein, control). These data
      indicate that DRG, generated through the activation of PLD, plays an important
      role in degranulation and oxidant release in adherent PMNs.

PMID- 8132531
TI  - Expression of beta 1-6-branched N-linked oligosaccharides is associated with
      activation in human T4 and T8 cell populations.
AB  - Activation of human T lymphocytes by phorbol 12-myristate 13-acetate and
      leukoagglutinin from Phaseolus vulgaris (L-PHA) results in important changes in N
      glycosylation. The most important event is the increase, in both T4 and T8 cells
      (especially the latter), of L-PHA+ structures characterized by beta 1-6-branching
      of complex-type oligosaccharides. Moreover, the existence of a CD4-mediated
      increase of these beta 1-6-branched structures on positively selected T4 cells,
      as compared with the negatively selected ones, suggests that the presence of
      these structures, not detectable on T8 resting cells, could be related to
      stimulation events triggered by both selection methods. This beta 1-6-branching
      on N-glycans, strongly associated with a metastatic phenotype in human and rodent
      tumors, is exhibited by numerous glycoproteins on stimulated cells, as shown by
      blot analysis.

PMID- 8132532
TI  - Mechanism of adenylate kinase. The conserved aspartates 140 and 141 are important
      for transition state stabilization instead of substrate-induced conformational
      changes.
AB  - The goal of this work is to evaluate the quantitative contribution of Asp-140 and
      Asp-141 to conformational changes and/or substrate stabilization in the catalysis
      by chicken muscle adenylate kinase (AK), by use of kinetic and structural
      analysis of the single alanine mutants D140A and D141A as well as the salt bridge
      double mutants R138M,D140A and R132M,D141A. The single mutants D140A and D141A
      displayed small increases in Km (6-12-fold) and moderate decreases in kcat (17-78
      fold). Kinetic analysis with the slowly reacting substrate system MgATP and dAMP
      suggested that the decrease in kcat is not caused by a decrease in the
      conformational step(s) relative to the chemical step. Most of the kinetic
      constants of the double mutants R138M,D140A and R132M,D141A are similar to those
      of the single mutants R138M and R132M, respectively. Detailed analysis by two
      dimensional NMR indicated no appreciable changes in the conformations of the free
      enzyme or the complex with MgAP5A (where AP5A is P1,P5-bis(5'
      adenosyl)pentaphosphate), for both single and double mutants. These results taken
      together suggest that Asp-140 and Asp-141 are unimportant for substrate-induced
      conformational changes in AK; their roles are mainly to assist Arg-138 and Arg
      132 in stabilizing the transition state. The structural results also suggest that
      AK is a flexible enzyme.

PMID- 8132533
TI  - Guanosine 5'-O-[S-(4-bromo-2,3-dioxobutyl)]thiophosphate and adenosine 5'-O-[S-(4
      bromo-2,3-dioxobutyl)]thiophosphate. New nucleotide affinity labels which react
      with rabbit muscle pyruvate kinase.
AB  - Three new reactive nucleotide analogues with bromo-keto substituents adjacent to
      a thiophosphate have been synthesized. Guanosine 5'-O-[S-(4-bromo-2,3
      dioxobutyl)]thiophosphate (GMPS-BDB), reacts covalently with rabbit muscle
      pyruvate kinase with complete inactivation and incorporation of 1.8 mol of
      reagent/mol of enzyme subunit. By contrast, the mono-keto compound, guanosine 5'
      O-[S-(3-bromo-2-oxopropyl)]thiophosphate (GMPS-BOP), causes no loss of pyruvate
      kinase activity. When the analogous adenosyl nucleotide derivatives are incubated
      with pyruvate kinase, the di-keto compound, adenosine 5'-O-[S-(4-bromo-2,3
      dioxobutyl)]thiophosphate (AMPS-BDB), rapidly effects inactivation, whereas the
      mono-keto compound, adenosine 5'-O-[S-(3-bromo-2-oxopropyl)]thiophosphate (AMPS
      BOP), causes no loss of activity. Complete protection against inactivation by
      GMPS-BDB is provided by phosphoenolpyruvate in the presence of K+ and Mn2+ and
      the amount of reagent incorporated (0.9 mol/reagent/mol subunit) is reduced to
      half that observed in the absence of protectants. Gas-phase sequencing of the
      tryptic peptides purified from inactive GMPS-BDB or AMPS-BDB-modified enzyme gave
      the cysteine-labeled peptides: C151DENILWLDYK161, and N162IC164K165 as the two
      major peptide products, with a smaller amount of N43TGIIC48TIGPASR55. Reaction in
      the presence of the protectants PEP, K+, and Mn2+ yielded Cys164 as the only
      labeled residue, indicating that inactivation is primarily due to modification of
      Cys151. We propose that GMPS-BDB (or AMPS-BDB), which may exist in enolized form
      in aqueous solution, functions as a reactive analogue of phosphoenolpyruvate and
      GDP (ADP) to target Cys151 in the active site of pyruvate kinase.

PMID- 8132534
TI  - Mutations of an active site threonyl residue promote beta elimination and other
      side reactions of the enediol intermediate of the ribulosebisphosphate
      carboxylase reaction.
AB  - The side chain of residue threonine 65 within the active site of
      ribulosebisphosphate carboxylase participates in a network of hydrogen bonds and
      ionic interactions involving the phosphate moiety attached to C-1 of the
      substrate. This residue was replaced with serine, alanine, and valine in the
      enzyme from Synechococcus PCC 6301. The mutant enzymes were stable, expressed
      abundantly by Escherichia coli, and retained the ability to form gel-filterable
      complexes with the reaction-intermediate analog, 2'-carboxyarabinitol-1,5
      bisphosphate. The substitutions reduced the kcat/Km(CO2) (where kcat is the
      substrate-saturated turnover rate) of the enzyme from 17- to 340-fold with the
      more radical substitutions causing more severe reductions. The CO2/O2 specificity
      also deteriorated progressively, the valine replacement causing a 2.3-fold
      reduction. In concert with these changes, a compound tentatively identified as 1
      deoxy-D-glycero-2,3-pentodiulose-5-phosphate, the product of beta elimination of
      the 2,3-enediol(ate) intermediate of the catalytic reaction, appeared among the
      reaction products in progressively increasing amounts. In the case of the valine
      substitution, it comprised 13% of the ribulose bisphosphate consumed. The mutant
      enzymes also partitioned more of their reaction flux to pentulose bisphosphate
      isomers of ribulose bisphosphate. By contrast, the diversion of carboxylated
      product to pyruvate, as a result of beta elimination of the three-carbon aci
      carbanion intermediate of the carboxylation reaction, was ameliorated by the
      replacements, the valine mutant showing a 5-fold improvement in this parameter.
      These observations focus attention on a geometric conflict which exists between
      the requirements for stabilization of the 5-carbon enediol(ate) and 3-carbon aci
      carbanion intermediates. This conflict must be resolved by a change in the angle
      of the C-1/bridge oxygen bond during each catalytic cycle. The network of
      hydrogen bonds involving the side chain of threonine 65 must play a crucial role
      in facilitating reaction of the enediol(ate) with the gaseous substrate and in
      shepherding this subsequent movement.

PMID- 8132535
TI  - Identification and characterization of cis-acting regulatory elements for the
      expression of the human aromatase cytochrome P-450 gene.
AB  - CYP19, the human aromatase cytochrome P-450 (P450arom) gene, encodes an enzyme
      which converts androgens to estrogens by three successive hydroxylation reactions
      by coupling with NADPH-cytochrome P-450 reductase. In the present study, we have
      characterized two cis-acting transcriptional regulatory elements of CYP19, termed
      as hATRE-1 (human aromatase cytochrome P-450 gene transcriptional regulatory
      element-1) ([sequence: see text]) and hATRE-2 ([sequence: see text]). These
      sequences are located between -2238 and -2214, and between -2141 and -2098
      relative to the major cap site of the gene, respectively. Transient expression
      analysis in human BeWo choriocarcinoma cells, in which CYP19 is expressed, shows
      that hATRE-1 represses the expression of the bacterial chloramphenicol
      acetyltransferase reporter gene driven by the promoter of CYP19, whereas hATRE-2
      enhances the reporter gene expression in response to 12-O-tetradecanoylphorbol 13
      acetate. Electrophoretic mobility shift analysis indicates that nuclear binding
      factors specific to hATRE-1 are present in BeWo cells, but not in HeLa cells nor
      in TYK-nu cells that lack the expression of CYP19. In contrast, nuclear binding
      factors to hATRE-2 are present not only in BeWo cells but also in the latter two
      types of cells. Nevertheless, hATRE-2 does not affect the reporter gene
      expression in HeLa cells and TYK-nu cells. These results indicate that hATRE-1
      and hATRE-2 are cis-acting transcriptional regulatory elements involving in the
      regulation of the cell type-specific expression of CYP19.

PMID- 8132536
TI  - Tagging secretory and membrane proteins with a tyrosine sulfation site. Tyrosine
      sulfation precedes galactosylation and sialylation in COS-7 cells.
AB  - Sulfation of proteins on tyrosines is a late Golgi modification that can be used
      to label proteins with [35S]sulfate for the analysis of post-Golgi transport. To
      extend the use of this modification to proteins not naturally sulfated, we fused
      a tyrosine sulfation site, the carboxyl-terminal nonapeptide of cholecystokinin
      precursor, to the carboxyl terminus of two normally unsulfated proteins: alpha 1
      proteinase inhibitor, a secretory protein, and subunit H1 of the
      asialoglycoprotein receptor; a type II membrane protein. The tagged proteins were
      efficiently sulfated in transfected COS-7 and Madin-Darby canine kidney cells.
      Specifically in COS-7 cells, the proteins were sulfated before they were
      galactosylated and sialylated and were converted to the mature forms with a half
      time of approximately 2-3 min. This is in contrast to other cell types in which
      tyrosine sulfation was found to be virtually the last modification of the Golgi
      apparatus. Our results suggest that tyrosine sulfation occurs before the trans
      Golgi in transfected COS-7 cells.

PMID- 8132537
TI  - Specific antibodies against the Zn(2+)-binding domain of clostridial neurotoxins
      restore exocytosis in chromaffin cells treated with tetanus or botulinum A
      neurotoxin.
AB  - Although tetanus and botulinum A neurotoxins are ineffective in cultured
      chromaffin cells, they will inhibit carbachol-induced release of noradrenaline
      provided they gain access to the cytosol either through artificial pores
      generated in the plasma membrane or by binding to incorporated exogenous
      gangliosides. The block of exocytosis persists for weeks followed by a slow
      recovery of cell function. When specific anti-botulinum A toxin antibodies are
      introduced into cells through pores after manifestation of the block by botulinum
      A neurotoxin, restoration of exocytotic function is accelerated and fully
      reestablished within 4 days. The same time course of restoration is seen with
      anti-tetanus toxin antibodies in cells poisoned by tetanus toxin. Since the light
      chains of the toxins are enzymatically active, we have introduced polyclonal and
      monoclonal anti-light chain antibodies into the cytosol. Of all light chain
      antibodies tested, only those directed against the peptide homologous to the zinc
      binding sequence, which is present in both neurotoxins, restored exocytosis
      regardless of which toxin caused the block. These results indicate that the zinc
      binding domain is directly involved in the interaction of the light chains with
      their substrates and that the toxins have to be present continuously to maintain
      the block.

PMID- 8132538
TI  - Location of two contact sites between human smooth muscle caldesmon and Ca(2+)
      calmodulin.
AB  - We measured Ca(2+)-calmodulin binding to expressed human caldesmon fragments by
      three techniques: tryptophan fluorescence enhancement, change in fluorescence of
      TA-calmodulin, and cosedimentation with calmodulin-Sepharose. Ca(2+)-calmodulin
      bound with similar affinity to peptide M73 (C714SMWEKGNVFSSPGF727, N terminus of
      domain 4b), to all the fragments of caldesmon containing this peptide, and also
      to H9 (Thr726-Val793), which did not contain this peptide (Kd = 0.2-0.8 microM).
      We conclude that Ca(2+)-calmodulin binds at two sites on caldesmon; site A is the
      sequence 715MWEKGNVFS723 previously identified by Zhan et al. (Zhan, Q., Wong, S.
      S., and Wang, C.-L.A. (1991) J. Biol. Chem. 266, 21810-21814), and site B is
      located nearer the C terminus of caldesmon. Ca(2+)-calmodulin binding at site B
      is coupled to reversal of caldesmon inhibition of actin-tropomyosin activated
      myosin MgATPase, while calmodulin binding at site A has no detectable function.
      H9 did not displace M73 from Ca(2+)-calmodulin, while the other fragments did.
      High concentrations of M73 (> 1000 x Kd) could not displace H9 bound to Ca(2+)
      calmodulin-Sepharose. Thus sites A and B in calmodulin are functionally separate.
      Analysis of overlapping expressed fragments indicates that site B is located in
      the sequence Thr726-Leu767, which includes Trp749. The minimal Ca(2+)-calmodulin
      binding sequence could be 744SRINEWLTK752.

PMID- 8132539
TI  - Nature of the rate-determining steps of the reaction catalyzed by the Yersinia
      protein-tyrosine phosphatase.
AB  - Product inhibition and 18O exchange experiments suggest that the Yersinia protein
      tyrosine phosphatase-catalyzed phosphate monoester hydrolysis proceeds through at
      least two different chemical steps, i.e. the formation and breakdown of a
      covalent phosphoenzyme intermediate. The pH dependence of kcat values is bell
      shaped, with the apparent pKa derived from the acidic limb of the profile at 4.6
      for both p-nitrophenyl phosphate and beta-naphthyl phosphate, whereas the
      apparent pKa derived from the basic limb of the profile is substrate-dependent,
      with apparent pKa values of 5.2 and 5.8 for p-nitrophenyl phosphate and beta
      naphthyl phosphate, respectively. Twelve aryl phosphates with leaving groups
      having pKa values from approximately 7 to 10 are also examined as substrates at
      two pH values. At pH 4.0, the beta lg values is effectively zero, whereas at pH
      7.5, a beta lg value of 0.16 is observed. Collectively, our results suggest that
      the rate-determining step under acidic conditions corresponds to the breakdown of
      the phosphoenzyme intermediate, whereas under more alkaline conditions, substrate
      effects also contribute to the rate-limiting step. A model is proposed for the
      mechanism of the Yersinia protein-tyrosine phosphatase-catalyzed reaction.

PMID- 8132540
TI  - Anti-metatype antibodies stabilize the fluorescein single-chain antibody 4-4-20
      complex against dissociation by hydrostatic pressure.
AB  - Hydrostatic pressure was used to promote dissociation of fluorescein (Fl) from
      single-chain antibody 4-4-20 (SCA 4-4-20). Fl fluorescence intensity was quenched
      by 97% upon binding to SCA 4-4-20. Increasing pressure to 2.4 kbar enhanced Fl
      fluorescence from the remaining 3% to 14-17%. The capacity of anti-metatype
      antibodies (anti-Met), which specifically recognize liganded anti-Fl antibodies,
      to protect against pressure-induced Fl dissociation was tested. Both polyclonal
      and monoclonal anti-Met antibodies protected against Fl dissociation, reducing
      the fluorescence intensity at 2.4 kbar from 14-17% to 6-8%. Additive effects of
      anti-Met antibodies in protection against pressure-induced Fl dissociation were
      suggested by the fact that a 2-fold molar excess polyclonal anti-Met reagent
      promoted additional protection relative to an equimolar amount. On the other
      hand, combination of different monoclonal anti-Met antibodies did not promote
      additive protection, suggesting recognition of overlapping metatopes by these
      monoclonals. The complex formed by SCA 4-4-20 and the Fl analog HPF was more
      sensitive to pressure than the Fl-SCA 4-4-20 complex. Addition of both polyclonal
      and monoclonal anti-Met antibodies reduced the Fl fluorescence recovery at 2.4
      kbar from 75% to 40-55%. In order to directly study binding of anti-Met
      antibodies to mAb 4-4-20, monoclonal anti-Met antibody 3A5-1 was labeled with 2
      dimethylaminonaphthalene-5-sulfonyl chloride (2,5-Dns-Cl) and Dns fluorescence
      anisotropy measured. Unliganded mAb 4-4-20 did not bind to 2,5-Dns-3A5-1 as
      indicated by the absence of measurable changes in Dns fluorescence anisotropy
      upon increasing mAb concentration. Addition of mAb 4-4-20 bound to Fl produced a
      sigmoidal increase in Dns anisotropy, compatible with association of the primary
      immune complex and 3A5-1. An affinity constant, K0.5, of 1.5 x 10(-7) M and a
      cooperativity coefficient (n) of 3.1 were calculated for formation of the Fl-mAb
      4-4-20 complex. The HPF-mAb 4-4-20 complex was also recognized by 2,5-Dns-3A5-1
      but with lower affinity, indicating that the monoclonal anti-Met 3A5-1
      distinguished between mAb 4-4-20 liganded to different haptens.

PMID- 8132541
TI  - Genomic structure and subcellular localization of MAL, a human T-cell-specific
      proteolipid protein.
AB  - Genomic DNA clones containing the T-cell-specific human MAL gene were isolated.
      Restriction and sequence analysis revealed four exons and three introns. Each
      hydrophobic segment of MAL together with its adjacent hydrophilic sequence
      correlates closely with one exon of the gene. RNase protection analysis revealed
      that the previously described MAL mRNA, which contains the sequences present in
      the four exons, is the mRNA species predominant in T-cells. A remarkable
      similarity was found between the hydrophobicity pattern of MAL and those of the
      peripheral membrane protein 22 (PMP-22) and the 16-kDa proteolipid of vacuolar
      H(+)-ATPase. Direct evidence supporting that MAL is a proteolipid was obtained by
      extracting bacterial lysates expressing recombinant MAL protein with lipophilic
      solvents used to extract lipids. The use of two different antibodies raised
      against distinct peptides from the MAL molecule has allowed the localization of
      MAL in the endoplasmic reticulum of T-cells. This subcellular localization is in
      agreement with the presence of a RWKSS motif in the COOH-terminal tail of MAL,
      next to its last putative transmembrane domain, that fits with one of the
      consensus sequences (RXKXX) for residency in the endoplasmic reticulum for
      transmembrane proteins. A possible function for MAL protein in T-cells is
      discussed based on its subcellular localization and the unique lipid-like
      properties of the proteolipid proteins.

PMID- 8132542
TI  - A beta-like DNA polymerase from the mitochondrion of the trypanosomatid Crithidia
      fasciculata.
AB  - The mitochondrial DNA in Crithidia fasciculata, a trypanosomatid parasite, is
      known as kinetoplast DNA. Kinetoplast DNA has a very unusual structure,
      consisting of several thousand minicircles and a few dozen maxicircles, all
      topologically interlocked into a giant network. There is one network within each
      cell's single mitochondrion. We previously purified a 43-kDa DNA polymerase from
      C. fasciculata mitochondria (Torri, A. F., and Englund, P. T. (1992) J. Biol.
      Chem. 267, 4786-4792). This enzyme has properties very different from those of a
      DNA polymerase gamma, the conventional mitochondrial polymerase. In addition to
      its small size, it is nonprocessive, has no detectable exonuclease activity, and
      has very low fidelity. In all of these respects, the polymerase resembles a DNA
      polymerase beta, a gap-filling enzyme thought to function in DNA repair in the
      nucleus of other eukaryotes. We speculate that this enzyme may have been
      specially imported into the C. fasciculata mitochondrion to repair the many gaps
      found in minicircles following their replication. This is the first example of a
      beta-like polymerase from the mitochondrion of any eukaryote.

PMID- 8132543
TI  - The nuclear localization signal of NGFI-A is located within the zinc finger DNA
      binding domain.
AB  - NGFI-A is an immediate-early gene that encodes a transcription factor whose DNA
      binding domain is composed of three C2H2 zinc fingers. To identify its nuclear
      localization signal (NLS), wild type NGFI-A and various mutants were transfected
      into COS cells and their cellular location assayed by indirect
      immunofluorescence. Although wild type NGFI-A was located exclusively within the
      nucleus, deletions lacking the highly basic zinc finger region were not
      efficiently translocated to the nucleus. However, DNA binding per se is not
      required for nuclear localization, as an NGFI-A mutant (A Y339G), which does not
      bind DNA, is still faithfully directed to the nucleus. To determine the minimal
      region(s) of NGFI-A sufficient to direct nuclear localization, the cellular
      location of various NGFI-A/beta-galactosidase fusion proteins was examined.
      Fusion proteins containing all three zinc fingers were found in the nucleus, but
      those containing only two zinc fingers were predominantly cytoplasmic. When the
      zinc finger structure was altered by mutating a zinc-chelating cysteine residue
      in any one of the three zinc fingers, the resulting domain was no longer capable
      of directing beta-galactosidase to the nucleus. Furthermore, the mutation of an
      arginine residue in the third zinc finger of NGFI-A, a position which is occupied
      by a leucine residue in most C2H2 zinc fingers, abolished nuclear localization,
      but had no effect on DNA binding. These studies suggest that NGFI-A contains a
      novel NLS which is dependent on the overall structure of the DNA binding domain
      and not solely upon its highly basic nature.

PMID- 8132544
TI  - The NAD(P)H:flavin oxidoreductase from Escherichia coli as a source of superoxide
      radicals.
AB  - The NAD(P)H:flavin oxidoreductase (encoded by the fre gene) of Escherichia coli
      is a soluble enzyme which, under aerobic conditions and together with NAD(P)H and
      flavins, generates superoxide radicals selectively. This was demonstrated from
      spin trapping experiments and from the ability of the flavin reductase to achieve
      a superoxide dismutase (SOD)-sensitive reduction of cytochrome c. The
      participation of the flavin reductase to O2-. generation in E. coli cells has
      been studied. Superoxide production in dialyzed cytosolic fraction of SOD
      deficient E. coli was stimulated by the addition of flavins. There was no
      stimulation in soluble extracts of flavin reductase-deficient strains. Moreover,
      using fusions of sodA promoter to lacZ, we showed that sodA transcription was
      diminished in flavin reductase-deficient E. coli and that the induction of MnSOD
      by flavin reductase was SoxRS-independent. These results suggest that the flavin
      reductase might: (i) in vivo, be an important cytosolic site of O2-. generation;
      (ii) in vitro, serve as a simple, efficient, and selective O2-. generator.

PMID- 8132545
TI  - Characterization of the malonyl-CoA-sensitive carnitine palmitoyltransferase
      (CPTo) of a rat heart mitochondrial particle. Evidence that the catalytic unit is
      CPTi.
AB  - A post 30,000 x g particulate fraction was isolated from rat heart. This mixed
      membrane fraction is enriched in a carnitine palmitoyltransferase which is
      sensitive to both malonyl-CoA and etomoxiryl-CoA at concentrations that inhibit
      the malonyl-CoA-sensitive carnitine palmitoyltransferase (CPTo/CPT-I) of intact
      mitochondria. Tritiated etomoxiryl-CoA labels two proteins with the same
      molecular weight as the labeled proteins from rat heart mitochondria. Malonyl-CoA
      sensitive carnitine palmitoyltransferase in the particulate fraction is stable to
      freeze-thawing, and the activity is not latent. These data show that the
      carnitine palmitoyltransferase associated with this particle is CPTo/CPT-I.
      Positive Western blots were obtained, with the particle using anti-CPTi/CPT-II at
      a molecular weight identical with the CPT1/CPT-II purified from rat heart
      mitochondria. Catalytic activity was purified to near homogeneity in
      approximately 40% yield. The purified protein has a molecular weight identical
      with CPTi/CPT-II, it cross-reacts with antibody against CPTi/CPT-II, it is not
      inhibited by malonyl-CoA or etomoxiryl-CoA, and mass spectral analyses of the
      tryptic peptides give the same molecular masses as CPTi/CPT-II, and, when mixed
      with equal amounts of CPTi/CPT-II, one uniform spot is found by two-dimensional
      electrophoresis. These data indicate that the catalytic subunit of CPTo/CPT-I is
      the same as CPTi/CPT-II. The average inhibition of the CPT of frozen-thawed
      particles is 71% by 50 nM etomoxiryl-CoA and 62% by 50 nM malonyl-CoA. The
      inhibitor sensitivity, but not the catalytic activity, is lost by solubilization
      in 1% Triton X-114; removal of Triton X-114 using Extracti-Gel D restores
      etomoxiryl-CoA and malonyl-CoA sensitivity (both 50 nM) of CPT to an average of
      77 and 48%, respectively. Consistent with previous reports, these results show
      that CPTo/CPT-I is NOT inactivated by detergents, rather detergents both
      desensitize it to malonyl-CoA and alter its Vmax. These data show the assumption
      that CPTo/CPT-I is inactivated by detergents is untenable.

PMID- 8132546
TI  - The sulfurtransferase activity and structure of rhodanese are affected by site
      directed replacement of Arg-186 or Lys-249.
AB  - Two mutants of the enzyme rhodanese that replace Arg-186 with Leu (R186L) or Lys
      249 with Ala (K249A) were prepared to test suggestions that these residues are
      involved in catalysis and structure. The predominant effect with R186L was
      functional, and Km for the sulfur donor, thiosulfate, increased from 3.7 mM to 73
      mM with a modest decrease in Vmax (672 IU/mg to 576 IU/mg). However, K249A was
      virtually inactive using thiosulfate, but it was active with thiosulfonates such
      as p-toluene-, 2-aminoethane-, or ethanethiosulfonate, and these compounds could
      be demonstrated to form persulfide-substituted rhodanese. Compared with wild type
      enzyme, K249A had (a) reduced stability, (b) comparable secondary structure, (c)
      more easily exposed hydrophobic surfaces, and (d) a core structure that denatured
      similarly to the wild type enzyme. Thus, Arg-186 and Lys-249 are important in
      rhodanese catalysis, and Lys-249 is particularly critical for substrate
      selectivity and protein stability. Finally, the results suggest that there can be
      active rhodanese species in vivo that will be undetected using thiosulfate as a
      sulfur donor.

PMID- 8132547
TI  - A pertussis toxin-insensitive calcium influx mediated by neuropeptide Y2
      receptors in a human neuroblastoma cell line.
AB  - Stimulation of neuropeptide Y (NPY) Y2 receptors induced an intracellular free
      Ca2+ ([Ca2+]i) increase in a human neuroblastoma cell line, CHP-234. When NPY in
      a Ca(2+)-free solution was applied, this increase was abolished. Depolarization
      with high KCl evoked no response, suggesting that the responses were not mediated
      by voltage-gated Ca2+ channels. There was no evidence that the NPY response
      consisted of a capacitative Ca2+ entry sensitive to internal Ca2+ store levels.
      The [Ca2+]i elevation was diminished by Ni2+, a blocker of Ca2+ entry. Mn2+
      induced a quench of the fura-2 fluorescence, which ceased promptly upon the
      removal of NPY, indicating that Ca2+ entry was linked tightly to receptor
      activation. Although thapsigargin- and ryanodine-sensitive Ca2+ stores were
      present, NPY-induced responses were not impaired by pretreatment with either
      drug. Furthermore, NPY had no effect on the thapsigargin-sensitive store.
      Pertussis toxin did not affect the NPY-stimulated [Ca2+]i increase, although it
      abolished the NPY-dependent inhibition of cAMP production. It is concluded that
      the Y2 receptors couple directly to receptor-operated Ca2+ channels without the
      involvement of intracellular Ca2+ stores. The results also indicate that Y2
      receptors can activate both pertussis toxin-sensitive and -insensitive mechanisms
      in the same cell.

PMID- 8132548
TI  - Identification of an essential cysteine residue in pyridoxal phosphatase from
      human erythrocytes.
AB  - Pyridoxal-specific phosphatase purified from human erythrocytes was inactivated
      by a variety of thiol-specific reagents in a time- and concentration-dependent
      manner. The presence of pyridoxal phosphate, a substrate, or inorganic phosphate,
      a competitive inhibitor, protected the enzyme from inactivation. Phosphatase
      inactivated by disulfide reagents was reactivated by the addition of excess
      dithiothreitol, indicating that the inactivation was due to formation of a mixed
      disulfide between the reagent and a free cysteinyl residue at or near the active
      site of the enzyme. Incorporation of either 1 mol of 5,5'-dithiobis(2
      nitrobenzoic acid) (DTNB), 0.6 mol of iodo[3H]acetate, or 0.6 mol of N
      [3H]ethylmaleimide per mol of subunit led to complete inactivation of the enzyme.
      High concentration of phosphate prevented the incorporation of DTNB and
      iodo[3H]acetate. Amino acid analysis of carboxymethylated enzyme and DTNB
      titration of the denatured phosphatase indicated that there may be only 1
      cysteinyl residue per subunit. Modification by iodoacetate did not affect the
      quaternary structure of the enzyme. The phosphatase modified by iodo[3H]acetate
      was subjected to trypsin digestion, and the resulting peptides were separated on
      a reverse phase C18 column. Two radioactive peaks were obtained and contained a
      peptide with the N-terminal sequence of Ala-Gln-Gly-Val-Leu-Phe-Asp-Cys(Cm)-Asp
      Gly-Val-Leu-X-Asn-Gly. Most of the radioactivity was released with Cys(Cm). These
      results indicate that the cysteinyl residue in this sequence is at or near the
      active site and is essential for activity. Residues 5-12 and 15 of this peptide
      are identical with a sequence of a yeast alkaline p-nitrophenylphosphatase, and
      the peptide has little homology with other mammalian phosphatases.

PMID- 8132549
TI  - Purification and biochemical characterization of Escherichia coli RecA proteins
      mutated in the putative DNA binding site.
AB  - Escherichia coli RecA protein plays a central role both in DNA repair and in
      recombination. We report biochemical properties of three new RecA proteins
      mutated at positions 199 (RecA694), 207 (RecA659), and 211 (RecA611) in the
      putative DNA binding site. RecA694 had a wild-type phenotype, whereas RecA611 and
      RecA659 were deficient in promoting both the self-cleavage of LexA repressor and
      the DNA-strand exchange reaction. In order to determine the origin of this
      inhibition, we examined the capacity of wild-type and mutant proteins to bind to
      single-stranded DNA (with and without single-stranded binding protein, SSB),
      double-stranded DNA, and ATP. DNA strand exchange defects were correlated with
      the inability of mutant proteins to displace SSB from DNA. For the recA659
      mutation this inhibition was reversed by equimolar wild-type protein. In
      contrast, mixtures of either wild-type/RecA659 or wild-type/RecA611 proteins
      remained deficient in LexA cleavage, suggesting that the dominant negative
      phenotype of the mutant proteins may be a consequence of the formation
      heterologous RecA complexes. Various mutations in the putative DNA binding site
      of RecA protein altered ATP binding, ATPase activity, displacement of SSB from
      single-stranded DNA, and protein-protein interactions. These results are
      consistent with the hypothesis that DNA binding to this site of RecA relays
      allosteric effects to several functional domains throughout the protein.

PMID- 8132550
TI  - Promoter elements of the mouse complement C4 gene critical for transcription
      activation and start site location.
AB  - We have explored the template and factor requirements for transcription of the
      gene encoding the murine complement component C4, expressed predominantly but not
      exclusively in liver and mononuclear phagocytes. Competition experiments in
      transcription assays with liver nuclear extracts show that the regions upstream
      of the transcription initiation site are largely dispensable for obtaining basal
      levels of accurately initiated transcription. Activated transcription, however,
      depends on three upstream regulatory factors, two of which interact with target
      sites seemingly related to NF-1 (region -112/-87) and USF (region -85/-64),
      respectively. A third upstream regulatory factor has been detected by the
      surprising finding that double-stranded oligomers covering sequences proximal to
      the cap site (position -48 to -7) stimulate transcription from the C4 promoter
      specifically. Results of nucleotide deletions and site-directed mutations argue
      that the C4 initiator, that is, the most critical element for basal and accurate
      transcription of the gene, overlaps the cap site and extends into the transcribed
      sequences (-1 to +12). Immediately downstream of this region lies a last
      regulatory element (within the +5 to +43 boundaries) indispensable for high
      levels of transcription. These data assume wider interest because the C4 promoter
      does not contain TATA or CAAT boxes and does not feature any of the elements
      characteristic of the TATA-less genes so far reported.

PMID- 8132551
TI  - Transcription factor (TF) IIB and TFIIA can independently increase the affinity
      of the TATA-binding protein for DNA.
AB  - The general transcription factors (TF) IIB and TFIIA are the first factors to
      associate with the TATA-binding protein (TBP) during formation of a transcription
      initiation complex on RNA polymerase II promoters. DNase I footprint titration
      was used to measure the effects of TFIIB and TFIIA on binding of TBP to a
      consensus TATA box. Under reaction conditions optimized for TBP-DNA complex
      formation, the presence of TFIIB increased affinity of TBP for the TATA box by
      2.5-fold, while TFIIA had no effect. When TBP binding conditions were sub
      optimal, both TFIIB and TFIIA independently increased TBP affinity by
      approximately 10-fold. Therefore both TFIIB and TFIIA have the intrinsic ability
      to directly increase the affinity of TBP for the TATA box. We suggest that this
      property of TFIIA and TFIIB may increase the range of conditions under which high
      affinity TBP-DNA interactions can occur and may therefore favor the formation of
      the preinitiation complex.

PMID- 8132552
TI  - Genomic footprinting and sequencing of human beta-globin locus. Tissue
      specificity and cell line artifact.
AB  - In order to gain further insights of the regulatory mechanisms of human beta-like
      globin gene switch during erythroid development, we have studied protein-DNA
      interaction in vivo at the human adult beta and fetal gamma globin promoters and
      their upstream enhancer, 5'HS-2, in purified human adult erythroblasts, in which
      the beta, but not gamma or epsilon, globin gene is actively transcribing. This
      genomic footprinting analysis of adult erythroblasts was carried out in
      conjunction with those of different non-erythroid human tissues, an
      embryonic/fetal erythroid cell line K562, and several non-erythroid human cell
      lines. Protein-DNA binding in the beta globin promoter, in particular at the two
      CACC promoter boxes and the CCAAT box, is detectable only in the adult
      erythroblasts. As expected, the gamma globin promoters were bound with specific
      nuclear factors in the expressing K562 cells, but not in non-erythroid tissues or
      cell lines. Relatively weak protein binding could also be detected in the
      vicinities of the two CCAAT boxes of the inactive gamma globin promoters in the
      adult erythroblasts. Although the patterns of nuclear factor-DNA interaction in
      vivo at the NF-E2/AP1, GATA-1, and GT-I motifs of 5'HS-2 enhancer in adult
      erythroblasts are similar to those in K562 cells, we have identified a previously
      undetected factor-binding motif of 5'HS-2 that is protected only in the adult
      erythroblasts. This motif is identical in sequence to the 3'-CACC box of the
      human beta globin promoter, and it is well conserved at the same location among
      all mammalian 5'HS-2 enhancers, suggesting an important regulatory role of this
      element in human beta globin gene transcription in adult erythroblasts. All of
      the above four motifs of 5'HS-2 are free of nuclear factor binding in non
      erythroid tissues, but two of them, NF-E2/AP1 and GT-I, are bound with factors in
      some non-erythroid cell lines but not in others. The functional implications of
      these genomic footprinting data and the tissue-specific CpG methylation patterns
      of the beta-like globin promoters we obtained by genomic sequencing are discussed
      in terms of positive and negative regulation of the human beta-like globin switch
      during erythroid development.

PMID- 8132553
TI  - Negative superhelicity promotes ATP-dependent binding of yeast RAD3 protein to
      ultraviolet-damaged DNA.
AB  - The RAD3 gene of Saccharomyces cerevisiae is required for excision repair of UV
      damaged DNA and is essential for cell viability. Remarkable homology exists
      between RAD3 and the human excision repair gene XPD, whose mutational
      inactivation underlies the cancer-prone disorder in xeroderma pigmentosum group D
      patients. Our previous work demonstrated that RAD3-encoded protein contains a DNA
      helicase activity. Here, we show that RAD3 binds preferentially to UV-damaged DNA
      over nondamaged DNA. Removal of pyrimidine dimers from damaged DNA by enzymatic
      photoreactivation does not affect binding, suggesting an affinity of RAD3 for
      pyrimidine (6-4) pyrimidone photoproducts. Damage-specific binding by RAD3 is
      strongly dependent on ATP and on the degree of negative superhelicity in DNA. The
      requirement of superhelicity in damage binding may target RAD3 to regions of DNA
      undergoing transcription, resulting in the preferential repair of these regions.
      The rad3 Arg-48 mutant protein, which lacks the DNA helicase activity, also binds
      UV-damaged DNA preferentially, indicating that DNA helicase and damage binding
      are two distinct and separable functional entities in RAD3.

PMID- 8132554
TI  - Demyristoylation of the major substrate of protein kinase C (MARCKS) by the
      cytoplasmic fraction of brain synaptosomes.
AB  - Myristoylated alanine-rich C kinase substrate (MARCKS) is a major substrate of
      protein kinase C, whose interaction with the plasma membrane is dependent on its
      phosphorylation by protein kinase C and on its N-terminal myristoylation. We
      describe a hitherto undescribed demyristoylation activity of the protein in
      cytoplasmic fraction of synaptosomes from bovine brain. The activity is dependent
      on ATP but independent from calcium. The formation of the demyristoylated form,
      characterized by an increased mobility on SDS gel (70 kDa instead of 85 kDa), was
      confirmed by mass spectrometry and amino acid sequencing. The molecular mass of
      the demyristoylated protein as well as the incorporation of radioactive phosphate
      from [gamma-32P]ATP indicated that one phosphoryl group was incorporated during
      the demyristoylation process. Calmodulin, which binds to the protein kinase C
      phosphorylation domain of MARCKS, inhibited the reaction in a calcium-dependent
      manner. These data suggest that the demyristoylation is regulated by the signal
      transduction pathways and that the two conserved domains of the protein, namely
      the N-terminal myristoylated region and the phosphorylation site domain, are
      functionally interdependent. The localization of MARCKS in the cells may be
      regulated not only by its phosphorylation with protein kinase C but also by a
      reversible myristoylation of the protein in situ.

PMID- 8132555
TI  - Mutational analysis of disulfide bridges in the type C atrial natriuretic peptide
      receptor.
AB  - The type C receptor (ANP-C or NPR-C) for the natriuretic peptides was
      demonstrated, by site-directed mutagenesis, to have an immunoglobulin-like
      disulfide bonding pattern that is very similar to that of the cytokine receptor
      superfamily. The mature form of ANP-C has a disulfide-linked homodimeric
      structure and contains 5 conserved cysteine residues per subunit, all in the
      extracellular domain. To identify the cysteine residue involved in the
      dimerization and further to determine the intramolecular disulfide bridges and
      their functional roles, cysteine to serine mutations of the 5 cysteine residues
      were constructed. An analysis of the mutant receptors expressed in COS-1 cells by
      125I-ANP binding assay and by measuring difference in their electrophoretic
      mobilities on sodium dodecyl sulfate-polyacrylamide gels indicated that 1) the
      first 4 cysteine residues are joined sequentially, forming the Cys104-Cys132 and
      Cys209-Cys257 loops of 29 and 49 residues, respectively; 2) the two disulfide
      linked loops are essential for the ligand binding activity; 3) the 5th cysteine
      residue Cys469 is used in the formation of covalently linked dimers; and 4) the
      covalent association of the subunit through the disulfide bond involving Cys469
      has no apparent influence on ligand-receptor interactions. The intramolecular
      disulfide bond Cys104-Cys132 was also confirmed by direct protein sequencing of
      tryptic fragments of purified ANP-C receptor. The secondary structural features
      revealed here will be useful in understanding the structure and function
      relationships of not only the dimeric ANP-C receptor, which has only a short
      cytoplasmic tail, but also the ANP-A (GC-A) and ANP-B (GC-B) receptor subtypes,
      which have a guanylate cyclase domain in their long cytoplasmic tail and have
      recently been shown to possess an oligomeric structure, since they have similarly
      spaced cysteine residues in their extracellular domains.

PMID- 8132556
TI  - A novel 39-kDa phosphoribosylpyrophosphate synthetase-associated protein of rat
      liver. Cloning, high sequence similarity to the catalytic subunits, and a
      negative regulatory role.
AB  - The rat liver phosphoribosylpyrophosphate (PRPP) synthetase exists as complex
      aggregates composed of the 34-kDa catalytic subunits (PRS I and II) and other 39-
      and 41-kDa proteins (Kita, K., Otsuki, T., Ishizuka, T., and Tatibana, M. (1989)
      J. Biochem. (Tokyo) 105, 736-741), which are termed here PRPP synthetase
      associated proteins (PAPs). We have cloned the cDNA for the major one of 39 kDa
      (PAP39) from a rat liver cDNA library. Nucleotide sequencing showed that the
      clone encoded 356 amino acids containing sequences of all five peptides derived
      from PAP39. Surprisingly, the deduced amino acid sequence is markedly similar to
      those of the 34-kDa catalytic subunits. Excluding two regions (about 45 residues
      in total), PAP39 has a 48% identity with PRS I. Northern analysis detected a
      major 1.9-kilobase transcript in all 16 rat tissues examined, and the relative
      amounts of PAP39 mRNA to PRS I mRNA varied with tissues. Covalent cross-linking
      experiments gave definitive evidence for molecular interaction of PAP39 with the
      catalytic subunits. Immunoprecipitation experiments revealed that all the
      catalytic subunits existed as complexes containing PAP39. When PAPs were
      eliminated from the rat liver enzyme complex by gel filtration in the presence of
      1 m MgCl2, a lyotrope, or by mild tryptic treatment, the enzyme activity of the
      remaining catalytic subunits increased. Based on these results, we propose that
      PAP39, the major component of PAPs, plays a negative regulatory role in PRPP
      synthesis and hence is an important factor controlling nucleotide syntheses in
      general.

PMID- 8132557
TI  - Thymidylate synthase is localized to the nuclear periphery in the yeast
      Saccharomyces cerevisiae.
AB  - To date, the organization of DNA precursor synthesis within eukaryotic cells
      remains unresolved. Previous studies have suggested the existence of a
      multienzyme complex that is responsible for DNA precursor synthesis and is
      associated with sites of replication within the nucleus. Contrasting this, other
      studies have proposed that DNA precursor synthesis occurs outside the nucleus. To
      further these studies, we have addressed the location where thymidylate synthase
      resides in yeast. Subcellular fractionation experiments indicate thymidylate
      synthase is associated with purified nuclei. Consistent with this,
      immunofluorescence analysis suggests that thymidylate synthase is situated at the
      nuclear periphery.

PMID- 8132558
TI  - Identification of a Pax paired domain recognition sequence and evidence for DNA
      dependent conformational changes.
AB  - Pax genes encode a family of developmentally regulated transcription factors that
      have been implicated in a number of human and murine congenital disorders, as
      well as in tumorigenesis (Gruss, P., and Walther, C. (1992) Cell 69, 719-722;
      Hill, R., and van Heyningen, V. (1992) Trends Genet. 8, 119-120; Chalepakis, G.,
      Tremblay, P., and Gruss, P. (1992) J. Cell Sci. Suppl. 16, 61-67; Maulbecker, C.
      C., and Gruss, P. (1993) EMBO J. 12, 2361-2367; Walther, C., Guenet, J. L.,
      Simon, D., Deutsch, U., Jostes, B., Goulding, M. D., Plachov, D., Balling, R.,
      and Gruss, P. (1991) Genomics 11, 424-434; Barr, R. G., Galili, N., Holick, J.,
      Biegel, J. A., Rovera, G., and Emanuel, B. S. (1993) Nature Genet. 3, 113-117).
      These genes are defined by the presence of an evolutionarily conserved DNA
      binding domain, termed the paired domain. The structure and the DNA binding
      characteristics of the paired domain remain largely unknown. We have utilized
      repetitive rounds of a polymerase chain reaction-based selection method to
      identify the optimal DNA binding sequences for the Pax-2 and Pax-6 paired
      domains. The results suggest that the paired domain family of peptides bind
      similar DNA sequences. Identification of this binding site has revealed an
      important structural clue regarding the mechanism of paired domain binding to
      DNA. CD and NMR structural analyses of the purified Pax-6 paired domain reveal it
      to be largely structureless in solution. Upon binding the recognition sequence,
      the complex becomes markedly less soluble and displays CD spectroscopic evidence
      of significant alpha-helical structure.

PMID- 8132559
TI  - N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis.
AB  - The imino sugar deoxynojirimycin and its alkylated derivatives are inhibitors of
      the N-linked oligosaccharide processing enzymes alpha-glucosidase I and II. These
      compounds are glucose analogues and have the potential to inhibit both
      glucosidases and glucosyltransferases. However, to date there has been no report
      of deoxynojirimycin or similar analogues inhibiting a mammalian
      glucosyltransferase. We have investigated the effects of deoxynojirimycin and its
      alkylated derivatives on the biosynthesis of glycolipids in HL-60 cells. We have
      found that the N-butyl and N-hexyl derivatives of deoxynojirimycin, but not
      deoxynojirimycin itself, are novel inhibitors of the glucosyltransferase
      catalyzed biosynthesis of glucosylceramide. This results in the inhibition of
      biosynthesis of all glucosylceramide-based glycosphingolipids. We have
      investigated the ability of one of these compounds, N-butyldeoxynojirimycin, to
      offset glucosylceramide accumulation in an in vitro Gaucher's disease model. This
      compound prevents lysosomal glycolipid storage and offers a novel therapeutic
      approach for the management of this and other glycolipid storage disorders.

PMID- 8132560
TI  - Intracellular analysis of in vitro modified HIV Tat protein.
AB  - Human immunodeficiency viruses HIV-1 and HIV-2 encode a Tat protein that
      specifically activates transcription from the viral long terminal repeat. To
      characterize the properties of the Tat proteins, we have expressed them in
      Escherichia coli. The purified Tat protein was biochemically analyzed and tested
      for activity upon electroporation into human cell lines. This protein
      electroporation was used for the intracellular analysis of in vitro modified Tat
      protein. Our results indicate that the transcriptionally active form of the Tat
      protein is a monomer. Furthermore, we found that Tat activity is dramatically
      inhibited by preincubation of the protein with strongly reducing agents. In
      contrast, no inhibitory effect was measured upon incubation with metal-chelating
      reagents. These results suggest that the cysteine residues of Tat are involved in
      the formation of intramolecular disulfide bonds.

PMID- 8132561
TI  - The release of Alzheimer's disease beta amyloid peptide is reduced by phorbol
      treatment.
AB  - Amyloid precursor protein (APP) is cleaved predominantly within the beta amyloid
      peptide (BAP) domain to release a non-amyloidogenic amino-terminal PN2 fragment.
      Treatment of cells with phorbol dibutyrate, an agent which activates protein
      kinase C, has been shown to increase the release of an amino-terminal fragment. A
      panel of mutant APP reporter constructs was expressed in which each of the
      potential phosphorylation sites located within the cytoplasmic domain of APP was
      replaced with alanine residues. Phorbol response patterns were unchanged for each
      of these mutants, suggesting that induced cleavage occurs independently of APP
      substrate phosphorylation. We find that phorbol (a) increases the release of a
      PN2 fragment that is consistent with the normal secretase activity, (b) decreases
      the release of a shorter amino-terminal APP fragment that is cleaved near the
      amino terminus of BAP, and (c) decreases the release of BAP which was identified
      based on electrophoretic mobility, epitope mapping, and radio-sequencing. These
      data demonstrate that pharmacological treatment can reduce the formation of BAP
      and suggests that protein kinase C activators could be developed as therapeutic
      agents to block BAP formation.

PMID- 8132562
TI  - Intrapeptide regulation of protein kinase C.
AB  - Protein kinase C is allosterically activated by diacylglycerol and
      phosphatidylserine. The enzyme is also activated by surprisingly dissimilar
      compounds such as short chained phosphatidylcholines and protamine sulfate. Here
      we show that conventional and nonconventional activators of protein kinase C beta
      II produce the same structural alteration. They expose Arg19 of the
      autoinhibitory pseudosubstrate domain to proteolysis. Molecular modeling of
      protein kinase C beta II's catalytic domain, based on the structure of the cAMP
      dependent kinase's catalytic domain, indicates that Arg19 is shielded by a
      cluster of acidic residues when the pseudosubstrate occupies the substrate
      binding site. Our biochemical data and structural modeling indicate a common
      mechanism of intrapeptide regulation of protein kinase C by all activators that
      involves release of the pseudosubstrate from the active site.

PMID- 8132563
TI  - Aromatic substrate molecules bind at the distal heme pocket of myeloperoxidase.
AB  - Binding of aromatic substrate molecules to myeloperoxidase has been investigated
      by EPR spectroscopy and model building. Binding of aromatic substrate molecules,
      such as phenol, p-cresol, resorcinol, and 4-amino salicylate, replaces the
      original rhombic high spin EPR spectrum of the ferric enzyme (g = 6.74, 5.18, and
      1.97) by another high spin signal (g = 7.04, 4.87, and 1.93) indicating that
      these substrate molecules bind near the heme center of the enzyme.
      Salicylhydroxamic acid and benzohydroxamic acid complexes of myeloperoxidase
      showed EPR spectra composed of high spin (g = 6.99, 4.93, and 1.95) and low spin
      (2.66, 2.22, and 1.81) signals. The hydroxamic side chains of these two
      substrates seem to interact with the heme iron. Model building based on the three
      dimensional structure of the enzyme (Zeng, J., and Fenna, R. E. (1992) J. Mol.
      Biol. 226, 185-207) revealed the presence of a hydrophobic pocket at the entrance
      of the distal heme cavity where the aromatic ring of these substrates can bind.
      Moreover, the six-membered ring portion of salicylhydroxamic acid and
      benzohydroxamic acid could bind to this hydrophobic pocket with the hydroxamic
      side chain placed between the imidazole of the distal His and the heme iron. The
      EPR results on lactoperoxidase and intestinal peroxidase also suggest the
      presence of an aromatic substrate binding site similar to that of
      myeloperoxidase.

PMID- 8132564
TI  - Cloning of the gp49B gene of the immunoglobulin superfamily and demonstration
      that one of its two products is an early-expressed mast cell surface protein
      originally described as gp49.
AB  - gp49 was originally defined as a 49-kDa surface glycoprotein preferentially
      expressed on mouse interleukin-3-dependent, bone marrow-derived mast cells, which
      are immature progenitor cells. A previously cloned cDNA (gp49A) indicated that
      gp49 was a member of the immunoglobulin (Ig) superfamily, and genomic DNA
      analysis indicated that two genes might encode a gp49 family. We have now
      characterized a 5.6-kilobase pair gene, gp49B, that encodes two novel gp49 cDNAs,
      gp49B1 and gp49B2. The two cDNAs are identical except that gp49B2 is missing exon
      6, which encodes a predicted transmembrane domain. In contrast to gp49A, gp49B1
      and gp49B2 have 32 additional amino acids at their C termini containing 4 of the
      6 consensus amino acids of the antigen receptor homology 1 motif found on several
      signal-transducing members of the Ig superfamily. When COS-7 cells were
      transfected with either the gp49B1 or gp49B2 cDNA, only the gp49B1 transfectants
      bound the B23.1 monoclonal antibody that originally defined gp49. Reverse
      transcriptase-polymerase chain reaction analysis of the transfectants established
      that both transcripts were expressed, suggesting that the product of the gp49B2
      transcript was not inserted in the plasma membrane. Thus, cloning of the gp49B
      gene has established the organization of one of the gp49 genes and provided
      evidence of alternate splicing of transcripts from that gene.

PMID- 8132565
TI  - Inhibition of membrane translocation of diphtheria toxin A-fragment by internal
      disulfide bridges.
AB  - Fragment A of diphtheria toxin is translocated to the cytosol when the toxin is
      presented to receptor-positive cells. The toxin binds to cell surface receptors
      through its B-fragment, and after endocytotic uptake, the low endosomal pH
      triggers translocation of the A-fragment across the membrane. Translocation can
      also be induced at the level of the plasma membrane by exposure to low pH medium.
      Based on the diphtheria toxin crystal structure, we made five double cysteine
      mutants of the A-fragment, each expected to form an intramolecular disulfide
      bond. Four of the double cysteine mutants efficiently formed an intramolecular
      disulfide bridge, and these same mutants showed a strong reduction in their
      translocating ability. The inhibition of translocation was observed both when the
      toxin was endocytosed and when translocation was induced by exposing surface
      bound toxin to low pH. The data indicate that extensive unfolding of the A
      fragment is required for translocation.

PMID- 8132566
TI  - Identification of membrane-associated proteins in Trypanosoma brucei encoding an
      internal, EARLRAEE amino acid repeat.
AB  - Differential screening of expression libraries with nonimmune and day 4-6 immune
      serum from naive rats infected with the protozoan Trypanosoma lewisi was used to
      identify potential cell surface protein coding genes. Several T. lewisi cDNAs
      that resulted were partially characterized and used to clone the homologues from
      Trypanosoma brucei. The nucleotide sequence of the cDNAs encoding the Tb-29 genes
      of the parasitic protozoan T. brucei obtained by this method (3557 nucleotides
      for Tb-291 and 8729 nucleotides for Tb-292) encoded predicted open reading frames
      of 1070 and 2550 amino acids, respectively. The Tb-29 proteins encoded a large
      domain with an octapeptide (EARLRAEE) repeat (79 repeats in Tb-291 and 60 in Tb
      292), which shared significant similarity with the octapeptide repeat of the S
      antigen of isolate NF7 of Plasmodium falciparum. The predicted amino acid
      sequence of the Tb-292 protein encoded potential transmembrane domains (eight in
      total). Indirect immunofluorescence using confocal image analysis and
      immunoelectron microscopy located the EARLRAEE proteins to a membranous network.
      The Tb-29 proteins were most abundantly distributed to the area surrounding the
      nucleus, the region between the nucleus and the flagellar pocket, and the region
      immediately underneath the flagellar pocket membrane. The subcellular
      distribution of Tb-29 proteins suggests that these proteins may provide a
      constituent associated with the cell's vesicular transport system.

PMID- 8132567
TI  - Genomic organization and chromosomal localization of a novel human hepatic
      dihydrodiol dehydrogenase with high affinity bile acid binding.
AB  - We previously characterized and cloned a unique human hepatic dihydrodiol
      dehydrogenase (DDH) that exhibits high affinity binding for bile acids (Stolz,
      A., Hammond, L., Lou, H., Takikawa, H., Ronk, M., and Shively, J. E. (1993) J.
      Biol. Chem. 268, 10448-10457). This hepatic dihydrodiol dehydrogenase
      demonstrates significant sequence homology with the cytosolic rat bile acid
      binder 3 alpha-hydroxysteroid dehydrogenase and other members of the monomeric
      oxidoreductase gene family. We now report the genomic organization and
      chromosomal localization of the human hepatic DDH in order to further define its
      physiological role and provide additional insight into the development of this
      gene family. The 15-kilobase human hepatic DDH gene was contained in an
      overlapping cosmid and lambda genomic clones and is composed of nine exons. A
      major transcriptional start site was determined to be 30 base pairs upstream from
      the ATG initiation methionine by both primer extension and S1 nuclease mapping
      studies. The human hepatic DDH gene was mapped by chromosomal in situ
      hybridization and analysis of human-mouse somatic cell hybrids to the tip of the
      short arm of chromosome 10 at p14. Strict conservation of the intron-exon
      junctions in the human hepatic DDH and two other members of the monomeric
      oxidoreductase gene family, aldose reductase and mouse major vas deferens protein
      suggests evolution from a common ancestral gene. Human hepatic DDH mRNA was
      identified in both human hepatoma Hep G2 and human lung carcinoma cell line NCI
      H322 by RN'ase protection; thus, these cell lines will be useful in examining the
      regulation of the gene.

PMID- 8132568
TI  - High affinity binding of the heat-stable protein kinase inhibitor to the
      catalytic subunit of cAMP-dependent protein kinase is selectively abolished by
      mutation of Arg133.
AB  - The two classes of physiological inhibitors of the catalytic subunit of cAMP
      dependent protein kinase are the regulatory subunits and the heat-stable protein
      kinase inhibitors (PKIs), and both share a common mechanism of inhibition. Each
      has a similar inhibitor site that resembles a peptide substrate, and this
      occupies the P-3 to P+1 portion of the peptide recognition site. However, in
      addition to this consensus site, each inhibitor requires a peripheral binding
      site to achieve high affinity binding. Arg134 and Arg133 lie on the surface of
      the catalytic subunit with Arg133 coming close to the amphipathic helix of PKI(5
      24) (Knighton, D. R., Zheng, J., Ten Eyck, L. F., Xuong, N.-h., Taylor, S. S.,
      and Sowadski, J. M. (1991) Science 253, 414-420). Replacement of Arg134 and
      Arg133 with Ala selectively abolishes the high affinity binding of PKI.
      Replacement of Arg133 alone is sufficient to give the same phenotype. In the
      presence of MgATP, the Kd,app, is increased from < 0.2 to 105 nM and, in the
      absence of ATP, the Kd is too large to be reliably measured. Based on the crystal
      structure, Arg133 hydrogen bonds to the P-7 backbone carbonyl of PKI(5-24).
      However, more importantly, it also contributes to the hydrophobicity of the P-11
      binding site in the C.PKI(5-24) complex. We predict that it is the perturbation
      of this hydrophobic pocket that accounts for the effects of this mutation. In the
      absence of peptide, Arg133 may help to stabilize Glu230, a buried carboxylate
      that binds to the P-2 Arg in the crystal structure of C.PKI(5-24). Replacement of
      Arg133 and Arg134 with Ala has little effect on catalysis using a heptapeptide
      substrate and has no effect on the inhibition of the catalytic subunit by the
      regulatory subunit. The results thus demonstrate that these two inhibitor
      proteins that both bind to the catalytic subunit with a high affinity utilize
      different sites on the enzyme to achieve tight binding. The gamma isoform of the
      catalytic subunit is insensitive to inhibition by PKI and in this isoform Arg133
      is replaced with Gln. We predict that this change accounts for the altered
      inhibitor properties of C gamma.

PMID- 8132569
TI  - Amino acid residues on human poliovirus receptor involved in interaction with
      poliovirus.
AB  - We have previously demonstrated that the N-terminal immunoglobulin-like domain
      (domain 1; 115 amino acids) of human poliovirus receptor (hPVR) is essential for
      poliovirus binding and infection to cells. To identify amino acids involved in
      the interaction with poliovirus, we constructed a number of cDNAs encoding mutant
      hPVRs whose domain 1 was partially derived from mouse PVR (mPVR) homolog, which
      does not serve as a binding site for poliovirus. Poliovirus binding and infection
      assays were performed on mouse L cells that express these chimera cDNAs. Anti
      hPVR monoclonal antibodies were employed to confirm the presence of mutant PVRs
      on the surface of mouse cells and to know conformational alteration of these
      PVRs. A significant decrease in efficiency of both poliovirus binding and
      infection to the cells was observed when one or a few amino acids of hPVR at
      Gly73, Ser74, Gln82, Leu99-Glu102, or Gln130-Ser132 were substituted by the
      corresponding amino acids of mPVR. Similar results were obtained when a 2-amino
      acid insertion of mPVR, which was missing in hPVR, was introduced at the
      corresponding site (between Arg98 and Leu99) of hPVR. These amino acids were
      highly conserved in functional PVRs of primates but not in unfunctional PVRs of
      rodents. These results indicate that the amino acids identified may have
      important roles in interaction of PVR with poliovirus that leads to the
      establishment of the virus infection. In the three-dimensional model of the
      domain 1 of hPVR, these amino acids are located on one side of the molecule. This
      suggests that the interaction with poliovirus occurs on this side of the domain
      1.

PMID- 8132570
TI  - A point mutation leads to an unpaired cysteine residue and a molecular weight
      polymorphism of a functional platelet beta 3 integrin subunit. The Sra
      alloantigen system of GPIIIa.
AB  - Recently, we described a low frequency platelet alloantigen on human platelet
      membrane glycoprotein (GP) IIIa, termed Sra, that was involved in neonatal
      alloimmune thrombocytopenia. To identify the molecular nature of the Sra
      alloantigen, we analyzed the nucleotide sequence of polymerase chain reaction
      amplified GPIIIa mRNA, and found a C2004-->T substitution in seven Sra positive
      individuals which results in an Arg636-->Cys polymorphism within the cysteine
      rich region of GPIIIa. Analysis of allele-specific recombinant forms of GPIIIa
      that differed only at amino acid residue 636 showed that anti-Sra alloantibodies
      reacted with the Cys636, but not the Arg636, recombinant form of GPIIIa.
      Interestingly, under reducing conditions, the Cys636 form of GPIIIa migrated with
      a slightly increased apparent molecular weight compared with the Arg636 form.
      Following treatment with Endoglycosidase H, both allelic forms of GPIIIa
      exhibited the same mobility, however the Sra epitope was lost. Sra positive
      platelets express the same number of GPIIb-IIIa complexes on their surface as
      wild-type Sra negative platelets, and also aggregate normally in response to a
      variety of platelet agonists. Based upon these results, we conclude that 1)
      GPIIIa residue 636 specifically controls the formation and expression of the Sra
      alloantigenic determinant, and 2) an unpaired cysteine residue alters the N
      linked glycosylation pattern of the extracellular domain of GPIIIa, but affects
      neither the degree of surface expression nor the adhesive function of the GPIIb
      IIIa complex.

PMID- 8132571
TI  - Insulin gene expression and insulin synthesis in mammalian neuronal cells.
AB  - To demonstrate the presence of de novo synthesis in central mammalian neurons, we
      cloned and sequenced a rabbit insulin cDNA from pancreas and used it to define
      sequences encoding insulin mRNA from postnatal rabbit brain. We observed
      transcription/elongation of nascent insulin transcripts, characterized the size
      of these transcripts, and localized them to specific neurons in certain
      catecholaminergic-rich areas of the central nervous system. RNase protection
      assays using a rabbit probe spanning a region from 14 bases 5' to the translation
      start site through all but 18 bases of the sequence encoding the A-chain of
      insulin showed two bands in rabbit brain RNA and only one band in pancreas. The
      larger band in brain was the same size as that in pancreatic RNA; the other was
      approximately 10 bases shorter. Because the sequence of a reverse transcription
      polymerase chain reaction product from brain RNA was identical to pancreatic RNA
      sequence in the region corresponding to the 3' region of the probe, the smaller
      band in brain is most consistent with a sequence mismatch in some brain mRNA in
      the region corresponding to the 5'-end of the probe. In situ hybridization
      localized insulin mRNA to anatomical regions involved with olfaction and higher
      association of the limbic system. High performance liquid chromatography,
      radioimmunoassay, and [35S]cysteine metabolic labeling of cultured neuronal and
      glial cells indicated extracellular secretion of immunoprecipitable insulin by
      neurons only. Presence of insulin transcripts within specific neurons with
      extracellular secretion of the peptide suggests a specialized biological role.

PMID- 8132572
TI  - Dissociation of endogenous cellular ceramide from NF-kappa B activation.
AB  - The participation of cell ceramide in tumor necrosis factor (TNF)-alpha
      stimulated NF-kappa B activation in Jurkat T cells and HL-60 cells was studied.
      TNF-alpha readily stimulated NF-kappa B activity in both cell lines as assayed by
      electrophoretic mobility shift assay and the use of a human immunodeficiency
      virus-chloramphenicol acetyltransferase reporter construct. However, TNF-alpha
      stimulation did not increase cell ceramide levels in either cell line. The
      exogenous addition of a short chain ceramide, N-acetylsphingosine, to Jurkat
      cells had no effect on NF-kappa B activity. When Jurkat T cells were exposed to
      the glucosylceramide synthase inhibitor, 1-phenyl-2-decanoylamino-3-morpholino-1
      propanol, endogenous ceramide levels increased 4-fold. The increase in ceramide,
      however, did not result in NF-kappa B activation nor did it potentiate TNF-alpha
      or phorbol ester-stimulated activity. We conclude that TNF-alpha-induced NF-kappa
      B activation occurs in Jurkat and HL-60 cell lines that do not demonstrate an
      increase in TNF-alpha-induced ceramide. Increasing ceramide levels by the
      addition of short chain ceramides or the use of a glucosylceramide synthase
      inhibitor can be dissociated from activation of NF-kappa B by TNF-alpha.

PMID- 8132573
TI  - Interaction between a geminivirus replication protein and origin DNA is essential
      for viral replication.
AB  - The geminivirus, tomato golden mosaic virus (TGMV), encodes one protein, AL1,
      that is absolutely required for viral DNA replication. AL1 interacts with the
      TGMV DNA genome by binding specifically to the viral origin of replication. We
      have investigated the nature and significance of AL1/origin interactions in vitro
      and in vivo by using competitive DNA binding and transient replication assays.
      Competition assays established that a 13-base pair (bp) element (5'
      GGTAGTAAGGTAG) containing two 5-bp direct repeat motifs separated by a 3-bp
      central core constitutes a high affinity AL1 binding site. DNAs containing intact
      3' repeat sequences plus core (TAAGGTAG and ccTAGTAAGGTAG) were stronger
      competitors for AL1 binding than DNAs containing intact 5' repeat sequences plus
      core (GGTAGTAA and GGTAGTA-AccTAG), thereby demonstrating that AL1 interacts
      differently with the repeat motifs. Replication in tobacco protoplasts
      established that the AL1 binding site is an essential cis-acting element for
      viral replication. No replication was detected for DNAs containing mutations in
      either of the repeat motifs of the AL1 recognition sequence when AL1 was provided
      in trans from a plant gene expression vector. In contrast, a DNA with a mutation
      in the 5' repeat motif (ccTAGTAAGGTAG) replicated when both AL1 and AL3, a TGMV
      protein involved in viral DNA accumulation, were provided in trans. No
      replication was detected for a DNA containing a mutation in the 3' repeat motif
      (GGTAGTAAccTAG) in the presence of AL1 and AL3. The in vitro and in vivo results
      suggest that binding of AL1 to the 3' repeat element is an essential step in DNA
      replication, while binding to the 5' repeat element may serve to enhance viral
      replication.

PMID- 8132574
TI  - Structure and genetics of the partially duplicated gene RP located immediately
      upstream of the complement C4A and the C4B genes in the HLA class III region.
      Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of
      gene duplication.
AB  - The correlation of many HLA-associated autoimmune and genetic diseases with the
      polymorphic complement C4 genes may be attributed to the presence of disease
      susceptibility genes in the close proximity of C4. We have cloned and
      characterized a pair of partially duplicated genes, RP1 and RP2, located 611 base
      pairs upstream of the human C4A and C4B genes, respectively. The putative RP
      protein, consisting of 364 amino acid residues, is basic and highly hydrophilic.
      There is a bipartite nuclear localization signal at residues 114-131 and
      therefore RP may be a nuclear protein. Northern blot analysis suggested that RP
      is ubiquitously expressed. The 5' region of the RP1 gene is CpG rich, which is a
      characteristic of housekeeping genes. The RP1 gene contains nine exons. Located
      in the fourth intron is a cluster of Alu elements, and a newly defined composite
      retroposon SVA with a SINE, multiple copies of GC-rich VNTRs and an Alu element
      altogether enclosed by direct terminal repeats. Members of SVA are also present
      in the complement C2 gene located about 20 kilobases upstream of RP1 in the HLA
      and in the cytochrome CYP1A1 gene. Determination of the DNA sequences for RP2
      from two different HLA haplotypes revealed identical hybrid sequences which
      resulted from fusion of RP with the tenascin-like Gene X and truncation of the 5'
      regions of both genes. Cumulative data suggest that the four tandemly arranged
      genes RP, complement C4, steroid 21-hydroxylase (CYP21), and Gene X altogether
      form a modular structure, RCCX. The number of RCCX modules varies from one to
      three or more in the population. Absence of the truncated genes RP2 and Gene XA
      have been detected in genomes with single RCCX modules. Duplication of the RCCX
      modules probably occurred before the speciation of great apes and humans as they
      contain the same breakpoint region of RP and Gene X gene duplication.

PMID- 8132575
TI  - G protein coupling to the thrombin receptor in Chinese hamster lung fibroblasts.
AB  - The specific involvement of G proteins in thrombin receptor-mediated Ca2+
      mobilization and DNA synthesis has been studied in single Chinese hamster lung
      fibroblasts (CCL39 cells) activated by the hexapeptide SFLLRN. Immunoblots
      performed with antibodies directed against the COOH terminus of G protein alpha
      subunits revealed that alpha q, alpha i, and alpha o were each present in CCL39
      cells. The Ca2+ response to SFLLRN was measured after microinjection of anti
      alpha q or anti-alpha o antibodies, which produced a total blockade in 71 and 46%
      of cells, respectively. A partial inhibition of the SFLLRN-induced Ca2+ response
      was observed in the remaining cells. The lag time between exposure of the cells
      to SFLLRN and the onset of Ca2+ mobilization was significantly longer (20-24 s)
      in cells microinjected with anti-alpha q- or anti-alpha o-antibodies than in
      control cells microinjected with preimmune serum (9 +/- 1 s). Moreover, the peak
      height of the Ca2+ response to SFLLRN was decreased by 36 and 73%, respectively
      in cells microinjected with anti-alpha q or anti-alpha o antibodies. SFLLRN
      induced DNA synthesis in growth-arrested CCL39 cells was also inhibited (44-78%)
      by prior microinjection of anti-alpha q or anti-alpha o antibodies. Anti-alpha 1
      antibodies had no effect on the SFLLRN-induced Ca2+ response or on DNA synthesis.
      These results provide direct evidence that the thrombin receptor in CCL39 cells
      is coupled to two different types of G proteins, Gq and Go, both causing Ca2+
      mobilization and mitogenesis.

PMID- 8132576
TI  - Association of peroxisome proliferator-activated receptor and Hsp72.
AB  - In an effort to understand the relationship between a 72-kDa heat shock protein
      (Hsp72) and peroxisome proliferator-activated receptors (PPARs), we have
      characterized their interaction using clofibric acid-Sepharose chromatography and
      co-immunoprecipitation with antisera raised against either rat PPAR (rPPAR) or
      Hsp72. First, we observed that both rPPAR and Hsp72 elute in a clofibrate
      dependent manner from the clofibric acid-Sepharose matrix. Second, we found that
      immunoprecipitation of either protein from solution resulted in the precipitation
      of the other. This result was obtained from rat liver cytosol, from Spodoptera
      frugiperda (Sf9) insect cells expressing rPPAR, and from reticulocyte lysate
      rPPAR expression systems. These results suggest that Hsp72 and rPPAR form a
      complex in vivo and that Hsp72 may play a role in the folding, subcellular
      localization, and/or signaling pathway of PPARs.

PMID- 8132577
TI  - Enhancement of interleukin-3-dependent mast cell proliferation by suppression of
      c-jun expression.
AB  - We have previously shown that protein kinase C (PKC) depletion is associated with
      an increase in the proliferation of interleukin 3 (IL-3)-induced mast cells. Here
      we show that the AP-1 components c-Jun and c-Fos are induced by IL-3. While c
      Jun's induction by IL-3 is totally dependent on PKC, c-Fos induction by IL-3 is
      only attenuated by PKC depletion. AP-1 binding activity was also induced by IL-3
      but this induction was PKC independent. These results indicated a possible
      involvement of c-Jun in the inhibition of IL-3-induced growth regulation. A
      support for this assumption came from experiments in which an increase in
      thymidine incorporation into mast cells was noted when c-jun antisense oligomers
      were administered to IL-3-treated cells. Since the only known effect of direct
      inhibition of c-Jun on proliferation rates in several cellular systems was a
      reduction of proliferation, we verified that our c-jun antisense oligomer could
      also inhibit proliferation rates in fibroblasts where such a repression was
      previously reported. Thus c-Jun has an inhibitory effect on IL-3 induction of
      mast cells proliferation that is distinct from its role in several other cellular
      environments. These observations reveal the involvement of AP-1 and its
      components in IL-3-induced signal transduction and the importance of the mast
      cell environment in determining their specific cellular function.

PMID- 8132578
TI  - Induction of cyclooxygenase-2 in rat vascular smooth muscle cells in vitro and in
      vivo.
AB  - Prostaglandins are synthesized from arachidonic acid by the rate-limiting enzyme
      cyclooxygenase (prostaglandin G/H synthase). Active cyclooxygenase is encoded by
      two distinct and independently regulated genes, termed cyclooxygenase-1 (cox1)
      and cyclooxygenase-2 (cox2). In this investigation, we examined the expression of
      cox1 and cox2 mRNA in rat aorta following balloon deendothelialization (BDE) in
      vivo and in rat aortic smooth muscle cells (SMC) after serum stimulation in
      vitro. Two h after BDE, rat aortic cox2 mRNA levels increased greater than 50
      fold relative to the lowest detectable levels on days 2 and 14. No message was
      detectable in non-BDE control rat aortas. Similar to the results found in vivo,
      cultured SMC exhibited a greater than 45-fold increase in cox2 mRNA levels after
      a 2-h exposure to serum. This increase was transient because cox2 levels declined
      at 4 and 8 h. In contrast, minimal changes in cox1 mRNA levels were observed
      after BDE or serum treatments. Increased levels of cox2 mRNA and corresponding
      protein synthesis led to an accumulation of total cyclooxygenase protein, which
      remained elevated 24 h after serum stimulation. Serum-treated SMC also generated
      greater amounts of cyclooxygenase-dependent metabolites than quiescent SMC as
      evidenced by marked increases in prostaglandin E2 content in conditioned media.
      This increase is associated with a 2.5-3.0-fold increased rate of arachidonic
      acid conversion to prostaglandin E2. Our data indicate that injury and serum
      stimulation differentially regulate mRNA and protein expression of two distinct
      cox genes in vascular SMC in vivo and in vitro. The findings suggest that the
      prostanoid responses after vascular injury are, in part, mediated by acute
      increases in cox2 mRNA and cyclooxygenase-2 protein.

PMID- 8132579
TI  - Limited proteolysis and active-site studies of the first multienzyme component of
      the erythromycin-producing polyketide synthase.
AB  - The domain structure of the 6-deoxyerythronolide B synthase 1 component of the
      erythromycin-producing polyketide synthase from Saccharopolyspora erythraea has
      been investigated using limited proteolysis and active-site labeling. Trypsin,
      elastase, endoproteinase Glu-C, and endoproteinase Arg-C were used to cleave the
      multienzyme, and the sizes of the resulting fragments were assessed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The location of fragments
      within the primary structure was established by N-terminal sequence analysis. The
      cleavage pattern followed domain boundaries previously predicted on the basis of
      sequence alignments, but many predicted interdomain regions were not cleaved,
      even under the harshest conditions used. Initial proteolysis generated three
      large fragments: an N-terminal fragment (about 60 kDa) housing an acyltransferase
      acyl carrier protein di-domain; a central fragment (about 90 kDa) containing a
      ketosynthase-acyltransferase di-domain; and a C-terminal fragment (about 220 kDa)
      containing the remaining six domains of the multienzyme, including the third
      acyltransferase. The intact multienzyme behaves as a dimer of molecular mass 660
      kDa on gel filtration; and the C-terminal fragment remains dimeric. However, the
      N-terminal and central fragments appear to be monomeric species. After
      proteolysis of the multienzyme, the N-terminal di-domain was found to be
      specifically labeled after incubation with [14C]propionyl-CoA, providing the
      first evidence for its proposed role as a "loading domain" for the propionate
      starter unit. In contrast, the other two fragments were specifically acylated by
      [14C]methylmalonyl-CoA, indicating that both the other two acyltransferases
      remain enzymatically active after proteolysis.

PMID- 8132580
TI  - Characterization of (6-4) photoproduct DNA photolyase.
AB  - Pyrimidine (6-4) pyrimidone photoproduct is the second most abundant UV
      photoproduct in DNA. Recently, it was reported that Drosophila melanogaster cell
      free extracts restored the biological activity of (6-4) photo-product-containing
      DNA in a light-dependent reaction (Todo, T., Takemori, H., Ryo, H., Ihara, M.,
      Matsunaga, T., Nikaido, O., Sato, K., and Nomura, T. (1993) Nature 361, 372-374)
      concomitant with the loss of (6-4) photoproduct antigenic sites and (6-4)
      photoproduct-caused alkali-labile sites. In the present study we show that the (6
      4) photoproduct but not its Dewar isomer is the substrate for the enzyme, that
      the enzyme has an action spectrum peak at 400 nm, and that the efficiency of
      repair per incident photon is very low compared with cyclobutane pyrimidine dimer
      photolyases. Furthermore, we provide evidence that the (6-4) photoproduct
      photolyase converts the photoproduct to unmodified bases probably through an
      oxetane intermediate.

PMID- 8132581
TI  - Characterization of binding of Gal beta 4GlcNAc-specific lectins from Erythrina
      cristagalli and Erythrina corallodendron to glycosphinogolipids. Detection,
      isolation, and characterization of a novel glycosphinglipid of bovine buttermilk.
AB  - The lectins from seeds of Erythrina cristagalli and Erythrina corallodendron were
      characterized for binding to glycolipids, using a chromatogram binding assay, a
      microtiter well assay, and glycolipids coated on erythrocytes. Both lectins bound
      to glycolipids having a terminal Gal beta 4GlcNAc sequence and also, with similar
      affinity, to glycolipids with terminal Fuc alpha 2Gal beta 4GlcNAc (blood group H
      determinant on a type 2 chain). All other substitutions of Gal beta 4GlcNAc
      tested abolished the binding. A binding epitope for the Erythrina lectins was
      considered by comparison of minimum energy conformations of binding and
      nonbinding glycolipids. A non-acid glycolipid, with lectin binding activity, was
      found in bovine buttermilk. By mass spectrometry and proton NMR spectroscopy it
      was shown to be a branched hexaglycosylceramide with the structure Gal beta 4Glc
      NAc beta 6(Gal beta 4GlcNAc beta 3)Gal beta 4Glc beta Cer. This glycosphingolipid
      has not been reported before.

PMID- 8132583
TI  - The COOH terminus of synaptotagmin mediates interaction with the neurexins.
AB  - The interaction of the synaptic vesicle protein, synaptotagmin, and the
      presynaptic alpha-latrotoxin receptor, a neurexin, has been proposed to be
      involved in docking of synaptic vesicles at active sites or modulation of
      neurotransmitter release. Here I report the investigation of the domain of
      synaptotagmin responsible for this interaction. Pieces of synaptotagmin
      containing the carboxyl terminus are capable of purifying neurexins from
      solubilized brain homogenates. Pieces as small as a synthesized peptide
      corresponding to the COOH-terminal 34 amino acids are capable of enriching
      neurexins 100-fold. The binding of neurexins to synaptotagmin is calcium
      independent and of moderate affinity. This COOH-terminal segment of synaptotagmin
      is conserved in all species characterized to date. Reflective of this, a
      synthetic peptide corresponding to the carboxyl terminus of Drosophila
      synaptotagmin is capable of purification of rat neurexins, suggesting the
      possibility that this interaction may also exist in Drosophila. I propose that
      the carboxyl terminus of synaptotagmin binds to the carboxyl terminus of the
      neurexins and that this interaction may mediate docking of synaptic vesicles or
      modulation of neurotransmitter release.

PMID- 8132582
TI  - Azotobacter vinelandii ferredoxin I. Alteration of individual surface charges and
      the [4FE-4S]2+/+ cluster reduction potential.
AB  - The structures of Azotobacter vinelandii ferredoxin I (AvFdI) and Peptococcus
      aerogenes ferredoxin (PaFd), near their analogous [4e-4S]2+/+ clusters, are
      highly conserved (Backes, G., Mino, Y., Loehr, T.M., Meyer, T.E., Cusanovich,
      M.A., Sweeney, W.V., Adman, E.T., and Sanders-Loehr, J. (1991) J. Am. Chem. Soc.
      11, 2055-2064). Despite these similarities, the reduction potential (E0') of the
      AvFdI [4Fe-4S]2+/+ cluster is more than 200 mV more negative than that of PaFd.
      We have tested the contribution that individual amino acid residues make to the
      control of E0' by converting residues in AvFdI into the corresponding residue in
      PaFd. Four mutations involved substitutions of negatively charged surface
      residues with neutral residues and two involved substitution of buried
      hydrophobic residues. All AvFdI variants were characterized by x-ray
      crystallography, absorption, CD, EPR, and 1H NMR spectroscopies and by
      electrochemical methods. For the F25I mutation, significant structural changes
      occurred that affected the EPR and 1H NMR spectroscopic properties of AvFdI and
      had a minor influence on E0'. For all other mutations there were no changes in
      reduction potential. Thus we conclude, that variations in charged surface
      residues do not account for the observed differences in E0' between the analogous
      [4Fe-4S]2+/+ cluster of PaFd and AvFdI. These differences are therefore most
      likely to be due to differences in solvent accessibility.

PMID- 8132584
TI  - A novel interferon-alpha-regulated, DNA-binding protein participates in the
      regulation of the IFP53/tryptophanyl-tRNA synthetase gene.
AB  - We have investigated the transcriptional response of the IFP53/tryptophanyl-tRNA
      synthetase gene to interferon-alpha (IFN-alpha). A single gamma-interferon
      activation site (GAS) in proximity to the transcription start sites was found to
      mediate the response of the IFP53 gene to IFN-alpha. This DNA element bound two
      distinct protein factors, alpha-interferon activation factor 1 (AAF1) and AAF2,
      which were rapidly activated in the cytoplasm of IFN-alpha-treated HeLa cells.
      AAF1, like the gamma-interferon activation factor, bound to the GAS from
      different IFN-responsive promoters and contained the 91-kDa ISGF3 protein (p91).
      However, in complexes with the IFP53 or Ly6A/E GAS, p91 was the only ISGF3
      protein, whereas in the case of the GBP GAS, the 48-kDa protein (p48) was also
      present. AAF2 was found to preferentially bind to the IFP53 GAS, but not at all
      to the GBP GAS, and contained no ISGF3 protein. Therefore, GAS-binding regulatory
      factors in the IFN-alpha response can either consist of proteins found in ISGF3
      or be formed by distinct proteins that are similarly linked to IFN-alpha-induced
      signal transduction.

PMID- 8132585
TI  - Production of gastrin-releasing peptide by a non-small cell lung carcinoma cell
      line adapted to serum-free and growth factor-free conditions.
AB  - Gastrin-releasing peptide is an important growth-modulating factor in developing
      lung epithelium. It is known to be produced by small cell carcinomas of the lung,
      and an autocrine loop involving gastrin-releasing peptide and its receptor has
      been demonstrated in many small cell lung tumors. We investigated whether such an
      autocrine loop could also be demonstrated in non-small cell lung carcinoma, since
      gastrin-releasing peptide is known to stimulate human bronchial epithelial cells,
      from which non-small cell tumors should emerge. We report here that gastrin
      releasing peptide is produced by a bronchiolo-alveolar carcinoma cell line (A549)
      adapted to serum-free and growth factor-free conditions. A549 cells adapted to
      these conditions, termed A549-R0 cells, display extensive membrane
      interdigitations, Golgi apparatus, and secretory-like granules, and grow as a
      mixture of attached colonies and floating cells. Gastrin-releasing peptide is
      present in the conditioned medium produced by A549-R0 cells. Colony formation of
      cells derived from a squamous cell carcinoma of the lung, 239T, was stimulated 9
      fold by A549-R0 conditioned medium or by authentic gastrin-releasing peptide,
      measured in serum-free conditions. The growth stimulatory activity was inhibited
      by a monoclonal antibody to gastrin-releasing peptide. Transcripts for receptors
      for the bombesin family of peptides were also demonstrated in A549-R0 cells and
      239T cells. These results demonstrate that non-small cell lung carcinomas can
      secrete gastrin-releasing peptide and can also respond to the peptide.

PMID- 8132586
TI  - Microtubule movement by a biotinated kinesin bound to streptavidin-coated
      surface.
AB  - Kinesin, an ATP-dependent microtubule motor, can be studied in vitro in motility
      assays where the kinesin is nonspecifically adsorbed to a surface. However,
      adsorption can inactivate kinesin and may alter its reaction kinetics. We
      therefore prepared a biotinated kinesin derivative, K612-BIO, and characterized
      its activity in solution and when bound to streptavidin-coated surfaces. K612-BIO
      consists of the N-terminal 612 amino acids of the Drosophila kinesin alpha
      subunit linked to the 87-amino acid C-terminal domain of the biotin carboxyl
      carrier protein subunit of Escherichia coli acetyl-CoA carboxylase. The C
      terminal domain directs the efficient post-translational biotination of the
      protein. We expressed K612-BIO at high levels using the baculovirus expression
      vector system and purified it to near-homogeneity. The expressed protein is
      completely soluble, and > 90% is bound by streptavidin. K612-BIO steady-state
      ATPase kinetics (KM,ATP = 24 microM, K0.5, microtubule = 0.61 mg ml-1, Vmax =
      approximately 25 s-1 head-1, 25 degrees C) are similar to those reported for
      intact kinesin. ATPase kinetics are not affected by the addition of streptavidin.
      Enzyme bound to a surface coated with streptavidin drove microtubule gliding in
      the presence of 2 mM ATP at 750 +/- 130 nm s-1 (26 degrees C). Activity was
      abolished by pretreatment of the surface with biotin, indicating that the
      microtubule movements are due to specifically bound enzyme. Motility assays based
      on specific attachment of biotinated enzyme to streptavidin-coated surfaces will
      be useful for quantitative analysis of kinesin motility and may provide a way to
      detect activity in kinesin derivatives or kinesin-like proteins that have not yet
      been shown to move microtubules.

PMID- 8132587
TI  - Proteolytic cleavage of vaccinia virus virion proteins. Mutational analysis of
      the specificity determinants.
AB  - Previous studies have suggested that cleavage of vaccinia virus core protein
      precursors occurs within the consensus tripeptide motif -A-G decreases X-. As an
      approach to delineate the sequence and structural features of the precursor
      polypeptides that are responsible for directing site-specific scission within
      this element, site-directed mutagenesis procedures were employed in concert with
      an in vivo trans-processing assay of the P25K: FLAG reporter plasmid. The results
      obtained suggest that residue occupancy at the P1' site (following the
      nomenclature of Schechter and Berger (Schechter, I., and Berger, A. (1976)
      Biochem. Biophys. Res. Commun. 27, 157-162), the positions at the amino- and
      carboxyl-proximal residues are indicated as P1, P2, etc., and P1', P2', etc.,
      respectively) was extremely permissive, with only a proline substitution blocking
      cleavage. In contrast, the permissible occupancy of the P1 (serine or alanine)
      and P2 (cysteine, serine, or asparagine) sites was extremely restricted. Analysis
      of P1/P2 double mutants supported this conclusion and suggested additional levels
      of combinatorial stringency. Insertion or deletion of sequences immediately
      adjacent (amino- or carboxyl-terminal) to the -A-G-X- motif completely abrogated
      cleavage, suggesting the presence of additional important structural
      determinants. Mutation of the conserved proline or basic amino acid residues in
      these regions had no effect on cleavage, whereas it appeared that the presence of
      a hydrophobic residue in the P4 site was required.

PMID- 8132588
TI  - In chromaffin cells, the mammalian Sec1p homologue is a syntaxin 1A-binding
      protein associated with chromaffin granules.
AB  - Membrane proteins of the synaptic vesicle and the presynaptic plasma membrane
      together with soluble proteins form a secretory fusion complex conserved from
      yeast to neurons (Sollner, T., Whiteheart, S. W., Brunner, M., Erdjument-Bromage,
      H., Geromanos, S., Tempst, P., and Rothman, J. E. (1993) Nature 362, 318-324).
      Two of the membrane proteins have been localized in chromaffin cells, which
      secrete catecholamines stored in chromaffin granules. Syntaxin 1A and 1B are
      found in a plasma membrane-enriched fraction, whereas synaptobrevin is
      concentrated on the granules. Recombinant syntaxin 1A has been used in an
      affinity chromatography assay to isolate syntaxin receptor proteins of the
      chromaffin granules. Solubilized granule membranes contain a single protein with
      high affinity for syntaxin 1A. Sequencing revealed partial homology with Sec1p, a
      hydrophilic yeast protein acting late in the secretory process. Genetic
      suppressor analyses predicted the interaction of Sec1p with Sso1p, a yeast
      homologue of syntaxin 1A, and with Sec4p, a homologue of rab3A (Aalto, M., Ronne,
      H., and Keranen, S. (1993) EMBO J. 12, 4095-4104). Although rab3A is present on
      chromaffin granules, we did not detect it bound to syntaxin 1A together with the
      mammalian Sec1p homologue (mSec1). The mSec1 peptide sequences are almost
      identical with respective sequences of a soluble protein, termed Munc-18,
      reported to be the only brain protein with affinity for recombinant syntaxin 1A
      (Hata, Y., Slaughter, C. A., and Sudhof, T. C. (1993) Nature 366, 347-351). The
      mSec1/Munc-18 may be a receptor protein for syntaxin 1A on the transmitter
      vesicles mediating their interaction with the plasma membrane in docking and
      fusion.

PMID- 8132589
TI  - Nucleoside diphosphate kinase enzyme activity of NM23-H2/PuF is not required for
      its DNA binding and in vitro transcriptional functions.
AB  - nm23 genes encode proteins that participate in tumor metastasis regulation and in
      various fundamental cellular processes, although the mechanisms remain undefined.
      All Nm23 proteins contain nucleoside diphosphate kinase (NDPK) activity whose
      significance to these regulatory effects is not yet evident. The protein product
      of the human nm23-H2 gene functions in vitro both as a nucleoside diphosphate
      kinase enzyme (NDPK-B; Gilles, A.-M., Presecan, E., Vonica, A. and Lascu, I.
      (1991) J. Biol. Chem. 266, 8784-8789) and as a transcription factor (PuF; Postel,
      E. H., Berberich, S. J., Flint, S. J. and Ferrone, C. A. (1993) Science 261, 478
      480). To understand the significance of these two biochemical activities to NM23
      H2 function, we have investigated the relationship between the DNA binding and
      transcriptional activity of NM23-H2 and its NDPK function. Using site-directed
      mutagenesis of the cDNA encoding NM23-H2, we have created a mutant substituting
      for the amino acid histidine 118, the presumed site of phosphorylation in the
      formation of the phosphoenzyme intermediate, the nonphosphorylatable amino acid
      phenylalanine. The H118F mutant protein is shown to be catalytically inactive as
      measured both in a radioisotopic assay that detects formation of the
      phosphorylated enzyme intermediate and in a coupled enzyme assay that indicates
      nucleoside diphosphate formation. These results confirm that histidine 118 is the
      critical residue for NDPK-B activity. In addition, the H118F mutant protein
      lacking enzymatic activity displayed normal DNA binding affinity for the c-myc
      promoter in electrophoretic mobility shift assays, and retained full
      transcriptional activity using the c-myc gene in vitro. These results indicate a
      lack of correlation between nucleoside diphosphate kinase activity of nm23-H2 on
      the one hand, and its DNA binding and transcriptional activity on the other,
      suggesting that the nm23-H2 gene encodes a bifunctional protein molecule.

PMID- 8132590
TI  - In vitro binding studies suggest a membrane-associated complex between erythroid
      p55, protein 4.1, and glycophorin C.
AB  - p55 is a palmitoylated peripheral membrane phosphoprotein of human erythrocytes.
      Primary structure of p55 includes a single copy of the SH3 motif, a COOH-terminal
      guanylate kinase domain, and an NH2-terminal domain of unknown function. Although
      the function of p55 is not known, interest in this component has been heightened
      by its similarity to the Drosophila tumor suppressor discs-large (dlg). In this
      report we provide evidence for the direct association of p55 with the NH2
      terminal 30-kDa domain of protein 4.1, a key component of the erythroid membrane
      skeleton. In addition, p55 also binds to the cytoplasmic domain of glycophorin C,
      a transmembrane protein of red blood cells. We also provide evidence
      demonstrating the direct association of the 30-kDa domain of protein 4.1 with the
      cytoplasmic domain of glycophorin C. Taken together, these results suggest the
      existence of a novel ternary complex at the erythroid plasma membrane involving
      protein 4.1, p55, and glycophorin C. Since isoforms of protein 4.1, p55, and
      glycophorin C are present in many non-erythroid cells, the binding interactions
      may be prototypical of similar associations that modulate cytoskeletal-membrane
      linkage of broad significance.

PMID- 8132591
TI  - Purified inner membrane protease I of yeast mitochondria is a heterodimer.
AB  - Inner membrane protease I is bound to the outer face of the yeast mitochondrial
      inner membrane and mediates the proteolytic maturation of cytochrome b2 and
      cytochrome oxidase subunit II. We have previously shown that one of its subunits
      is a 21.4-kDa integral membrane protein encoded by the nuclear IMP1 gene. We have
      now purified the active protease approximately 300-fold from yeast mitochondria.
      It has an apparent molecular weight of 35,000 and contains not only Imp1p but
      also a previously unrecognized 19-kDa subunit. Partial amino acid sequencing
      identifies this subunit as the product of the recently described IMP2 gene
      (Nunnari, J., Fox, T., and Walter, P. (1993) Science 262, 1997-2004).

PMID- 8132592
TI  - Identification of a region of the H,K-ATPase alpha subunit associated with the
      beta subunit.
AB  - The gastric H,K-ATPase consists of an alpha, beta heterodimer. To determine which
      part of the alpha subunit is associated with the beta subunit, hog gastric
      vesicles were trypsinized, which left most of the beta subunit undigested. The
      vesicles were solubilized with either C12E8 (polyoxyethylene 8 lauryl ester) or
      Nonidet P-40 and then passed over a wheat germ agglutinin column, which retained
      the beta subunit. Among the fragments of membrane spanning segments obtained by
      digestion in the absence of K+, only one peptide fragment of the alpha subunit
      coeluted with the beta subunit, representing only the M7 and M8 membrane spanning
      segments of the alpha subunit along with their extracytoplasmic connecting loop.
      With K+ present during digestion, the fragments at 19-21 kDa and at 9.4 kDa were
      retained on the column, representing the M7 to C-terminal end and the M5/loop/M6
      sector of the enzyme. These results provide biochemical evidence that a region of
      the alpha subunit containing the M7/loop/M8 sector is bound to the beta subunit
      under both digestion conditions; but when the C-terminal 180-amino acid sector of
      the alpha subunit remains intact, as found in the presence of K+, there is an
      additional retention of the M5/loop/M6 sector of the alpha subunit.

PMID- 8132594
TI  - Regulation of N-glycosylation. Long term effect of cyclic AMP mediates enhanced
      synthesis of the dolichol pyrophosphate core oligosaccharide.
AB  - The influence of 8-bromo-cAMP on N-glycosylation in JEG-3 choriocarcinoma cells
      was investigated using the octanoyl-tripeptide (OTP; N-octanoyl-asparagyl-125I
      tyrosyl-threonine amide) as glycosyl acceptor. In cells pretreated with 8-bromo
      cAMP (2.5 nM to 1 mM), the amount of glycosylated OTP released into the culture
      medium was increased up to 35-fold. Under the same conditions, a 23-fold higher
      quantity of the glycoprotein hormone human chorionic gonadotropin was secreted.
      Preincubation of 10-90 min with 250 microM 8-bromo-cAMP caused only a 2-fold
      increase of the total amount of glycosylated OTP, whereas it was approximately 20
      fold higher when the pretreatment was extended to 40 h. This strongly suggests
      involvement of gene activation rather than cAMP-mediated phosphorylation. The
      specific activity of the oligosaccharyltransferase, as well as the mRNA levels of
      ribophorin I and II (presumptive subunits of the enzyme), remained unchanged. In
      pulse-chase experiments, [3H]mannose incorporation into dolichol-linked
      Glc3Man9(GlcNAc)2 was up to 20-fold higher in cells pretreated with 8-bromo-cAMP
      (250 microM, 40 h). The radioactivity was chased from the lipid-linked
      oligosaccharide pool and shifted to the glycoprotein fraction 10 times more
      rapidly in the pretreated cells. The flux of [3H]mannose through the dolichol
      phosphate mannose pool was only slightly affected by the 8-bromo-cAMP
      pretreatment. Our investigations show that the oligosaccharyltransferase activity
      in JEG-3 cells is not rate-limiting. N-Glycosylation seems to be controlled by
      the amount of lipid-linked core oligosaccharide. The size of the lipid-linked
      core oligosaccharide pool, as well as the flux through, is markedly increased by
      pretreatment with 8-bromo-cAMP.

PMID- 8132593
TI  - Interactions between Ca(2+)-mobilizing receptors and their G proteins in
      hepatocytes.
AB  - In hepatocytes, different receptors that share an ability to stimulate inositol
      1,4,5-trisphosphate formation by activating guanine nucleotide-binding proteins
      (G proteins) evoke Ca2+ signals that are characteristic of the receptor that
      evoked them. High affinity, guanine nucleotide-sensitive binding of agonists to
      their receptors provides a convenient means of assessing receptor-G protein
      interactions. We used these methods to examine the extent to which different
      Ca(2+)-mobilizing receptors share G protein pools. Although our earlier results
      (Dasso, L. L. T., and Taylor, C.W. (1992) Mol. Pharmacol. 42, 453-457) showed
      that activated V1-vasopressin receptors prevented alpha 1-adrenoreceptors from
      associating with G proteins, our present results show that neither alpha 1
      adrenergic agonists nor angiotensin II influences the interaction between V1
      receptors and their G proteins. This asymmetric scavenging of G proteins by alpha
      1-adrenoreceptors and V1 receptors is not a consequence of there being more of
      the latter and may result either from V1 receptors binding more tightly to G
      proteins or from their ability to interact with a second G protein pool. We
      speculate that the different interactions among V1 receptors, alpha 1
      adrenoreceptors, and their G proteins contribute to the differently shaped Ca2+
      spikes evoked by these receptors.

PMID- 8132595
TI  - 1,25(OH)2-vitamin D3 signal transduction in chick myoblasts involves
      phosphatidylcholine hydrolysis.
AB  - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) rapidly stimulates the biphasic formation
      of diacylglycerol (DAG) in chick myoblasts. Neomycin (0.5 mM), an inhibitor of
      phosphoinositide hydrolysis, abolished the first phase (1 min) but had no effect
      on the second 1,25(OH)2D3-induced DAG peak (5 min). In myoblasts prelabeled with
      [3H]choline, 1,25(OH)2D3 increased the release of [3H]choline (maximally at 5
      min), with a concomitant decrease in phosphatidylcholine and the absence of
      significant changes in phosphocholine. 1,25(OH)2D3 caused a significant increase
      in phosphatidylethanol (PEt) formation in myoblasts in the presence of 1.5%
      ethanol. The effects of 1,25(OH)2D3 were time- and dose-dependent (10(-11) to 10(
      8) M) and specific as 25OHD3 and 24,25(OH)2D3 failed to accumulate PEt. 12-O
      Tetradecanoylphorbol-13-acetate failed to accumulate PEt. 12-O
      Tetradecanoylphorbol-13-acetate also stimulated PEt formation. The combination of
      1,25(OH)2D3 and 12-O-tetradecanoylphorbol-13- acetate was more effective than
      either compound alone. Neither the PKC inhibitor H7 nor PKC down-regulation
      blocked the hormone-induced increase in PEt. The effects of 1,25(OH)2D3 were,
      however, inhibited in the absence of extracellular Ca2+ (+EGTA) and by nifedipine
      and verapamil, whereas the Ca2+ ionophore A23187 also increased PEt generation.
      The data support the notion that 1,25(OH)2D3 triggers the hydrolysis of
      phosphatidylcholine in myoblasts through a Ca(2+)-dependent, PKC-independent,
      phospholipase D-catalyzed mechanism.

PMID- 8132596
TI  - Oligomeric structure, enzyme kinetics, and substrate specificity of the
      phycocyanin alpha subunit phycocyanobilin lyase.
AB  - Phycobiliproteins carry linear tetrapyrrole chromophores (bilins) thioether
      linked to specific cysteine residues. The process of bilin attachment to
      apoprotein in vivo has been characterized for only one bilin attachment site on
      one phycobiliprotein, that on the alpha subunit of phycocyanin (alpha PC). In the
      cyanobacterium Synechococcus sp. PCC 7002, the addition of phycocyanobilin to apo
      alpha PC is catalyzed by the protein products of the cpcE and cpcF genes. We have
      purified and further characterized the recombinant CpcE and CpcF proteins. CpcE
      and CpcF form an enzymatically active 1:1 complex (CpcEF), stable to size
      exclusion chromatography. CpcEF causes a reduction in alpha PC fluorescence and
      strongly affects its absorption spectrum but has no effect on the beta subunit.
      The CpcEF bilin addition activity exhibits simple Michaelis-Menten kinetics with
      respect to the apo-alpha PC and to bilin. CpcEF also catalyzes the addition of
      phycoerythrobilin to apo-alpha PC; phycoerythrobilin is thought to be on the
      biosynthetic pathway of phycocyanobilin. CpcEF shows a preference for
      phycocyanobilin relative to phycoerythrobilin, both in binding affinity and in
      the rate of catalysis, sufficient to account for selective attachment of
      phycocyanobilin to apo-alpha PC.

PMID- 8132597
TI  - Quantitation of interaction of anti-metatype monoclonal antibodies specific for
      the variable regions of a high affinity liganded monoclonal antibody.
AB  - Four hamster monoclonal anti-metatype antibodies were characterized in terms of
      their binding properties with liganded murine monoclonal single-chain
      antifluorescein antibody 4-4-20. Based on induced delays in the rate of ligand
      (fluorescein) dissociation upon the binding of each monoclonal anti-Met antibody,
      apparent Kd values were determined for monoclonal antibodies 3A5-1, P1E11, 4A6,
      and 2C3 (3.6 x 10(-8), 3.6 x 10(-8), 5.0 x 10(-8), and 2.6 x 10(-7) M,
      respectively). The interaction of hamster monoclonal antibody 3A5-1 with liganded
      SCA 4-4-20 and IgG 4-4-20 was also evaluated on the basis of deuterium oxide
      exchange to assess the relative ability of each antibody to stabilize the
      intrinsic dynamics of the variable domains of the single-chain molecule. The
      results indicated a correlation between the apparent Kd of the monoclonal anti
      Met antibody and the degree of delay in the rate of ligand dissociation from the
      primary antibody.

PMID- 8132599
TI  - Identification of the high affinity binding site of transforming growth factor
      alpha (TGF-alpha) for the chicken epidermal growth factor (EGF) receptor using
      EGF/TGF-alpha chimeras.
AB  - Human epidermal growth factor (hEGF) and human transforming growth factor-alpha
      (hTGF-alpha) are structurally related growth factors that share relatively little
      sequence homology. They both exert their biological action by binding to the cell
      surface EGF receptor. hEGF and hTGF-alpha bind with similar affinity to the hEGF
      receptor, but hEGF binds with an approximately 100-fold lower affinity to the
      chicken EGF receptor compared with hTGF-alpha. To map the region in hTGF-alpha
      that confers its ability to bind with high affinity to the chicken EGF receptor,
      10 hybrids of hEGF and hTGF-alpha were constructed by exchanging domains bordered
      by the third, fourth, and sixth conserved cysteine residues. The activity of the
      expressed chimeric proteins was determined by their ability to compete with 125I
      labeled mouse EGF for binding to NIH-3T3 cells transfected with the hEGF
      receptor. Subsequent binding competition studies of NIH-3T3 cells transfected
      with the chicken EGF receptor showed that chimeras carrying TGF-alpha sequences
      COOH-terminal of the sixth cysteine have a high affinity for this receptor,
      similar to hTGF-alpha. In contrast, chimeras with EGF sequences in this COOH
      terminal domain have only low binding affinity, similar to hEGF. We conclude that
      the COOH-terminal linear region of hTGF-alpha is important for its high affinity
      interaction with the chicken EGF receptor.

PMID- 8132598
TI  - Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic GMP
      dependent protein kinase.
AB  - Cyclic GMP (cGMP) inhibits intracellular calcium ([Ca2+]i) mobilization in
      vascular smooth muscle cells by a mechanism that is not well understood. Because
      several studies suggest that cGMP inhibits inositol 1,4,5-trisphosphate (IP3)
      action, we examined the effects of cGMP-dependent protein kinase on IP3 receptor
      phosphorylation. The purified IP3 receptor was phosphorylated using either the
      cGMP- or cAMP-dependent protein kinase in vitro. Phosphorylation was time
      dependent and stoichiometric using both kinases. Two-dimensional phosphopeptide
      mapping, high performance liquid chromatography analysis, and amino acid analysis
      showed that identical sites were phosphorylated using either kinase, and
      identified serine 1755 as the site of phosphorylation. The synthetic peptide
      corresponding to serine 1755 (GRRESLTSFG) was phosphorylated with aKm in the
      range of 30-40 microM by both kinases. The kinetic analysis revealed that this
      peptide substrate is the best substrate described for cGMP kinase to date.
      Vascular smooth muscle cells prelabeled with [32P]orthophosphate and treated with
      atrial natriuretic peptide or sodium nitroprusside to elevate cGMP also resulted
      in increased labeling of the IP3 receptor. Phosphorylation of IP3 receptor by
      cGMP kinase may regulate the function of IP3 receptor in vascular smooth muscle
      cells and contribute to the effect of cGMP to regulate intracellular calcium
      levels.

PMID- 8132600
TI  - Age-related increase in liver retinyl palmitate. Relationship to lipofuscin.
AB  - Lipofuscin is a general term assigned to fluorescent material that accumulates in
      cells as they age. It is apparent from this study that the fluorescent intensity
      of detergent-solubilized liver from Fisher-344 rats increased as a function of
      age. The fluorophore responsible for this increase was extracted with methanol
      and could be resolved from other cellular components when the methanol extracts
      were chromatographed over a reverse phase column. This compound was identified as
      retinyl palmitate and was found to increase throughout the entire life of the
      Fisher-344 rat (2-24 months), from a value of 0.26-1.77 mg/g of liver. In
      addition, the results presented here demonstrate that concentration, time between
      extraction and analysis, exposure to light, and degree of purity affect the
      observed fluorescent properties of retinyl palmitate. These factors affect many
      fluorophores and are likely to be, at least in part, responsible for the
      multiplicity of reported properties of lipofuscin. As has been reported for
      lipofuscin, retinyl palmitate accumulates in intracellular granules and exhibits
      fluorescence between 450 and 600 nm. Due to these similarities, the relationship
      between retinyl palmitate and lipofuscin warrants further investigation.

PMID- 8132601
TI  - Hydrolysis of phosphatidylinositol 3,4-bisphosphate by inositol polyphosphate 4
      phosphatase isolated by affinity elution chromatography.
AB  - Inositol polyphosphate 4-phosphatase is a monomeric 110-kDa protein that
      hydrolyzes two substrates in the inositol phosphate pathway. Inositol 3,4
      bisphosphate is converted to inositol 3-phosphate, and inositol 1,3,4
      trisphosphate is converted to inositol 1,3-bisphosphate. We have exploited the
      fact that inositol hexasulfate inhibits the enzyme to devise an affinity elution
      scheme from a Mono S cation exchange column that resulted in an 11,300-fold
      purified preparation of rat brain 4-phosphatase. The resulting 4-phosphatase
      hydrolyzed phosphatidylinositol 3,4-bisphosphate to phosphatidylinositol 3
      phosphate with a first order rate constant 120-fold greater than that for
      inositol 3,4-bisphosphate and 900-fold greater than that for inositol 1,3,4
      trisphosphate. This is now the third example wherein the same enzyme hydrolyzes
      both an inositol lipid and its analogous inositol phosphate.

PMID- 8132602
TI  - Visual arrestin binding to rhodopsin. Intramolecular interaction between the
      basic N terminus and acidic C terminus of arrestin may regulate binding
      selectivity.
AB  - Visual arrestin plays an important role in quenching phototransduction via its
      ability to preferentially bind to phosphorylated light-activated rhodopsin (P
      Rh*). Recently we proposed a mechanism for the binding of visual arrestin to P
      Rh* that helps to explain the nature of the conformational changes in arrestin
      observed upon binding. This mechanism involves a multisite interaction between
      arrestin and P-Rh* and implies an interaction between the C-terminal and N
      terminal domains of arrestin. To obtain further insight into the mechanism of
      arrestin-rhodopsin interaction we have characterized the ability of polyanions to
      inhibit the interaction of wild type and mutant arrestins to different functional
      forms of rhodopsin. These studies reveal that: 1) heparin is most potent at
      inhibiting arrestin binding to dark phosphorylated rhodopsin > light-activated
      rhodopsin > P-Rh*; 2) C-terminal deletions in arrestin increase arrestin
      sensitivity to heparin inhibition while an N-terminal deletion (residues 2-16)
      decreases heparin inhibition; 3) the sensitivity of chimeric arrestins to heparin
      inhibition is determined by the origin of the N terminus of the chimera; and 4)
      heparin also inhibits arrestin binding to truncated 329G-Rh*, suggesting it does
      not mimic the phosphorylated C terminus of rhodopsin. Taken together, these data
      suggest that heparin mimics the regulatory acidic C terminus of arrestin. Since
      the basic N-terminal region of arrestin appears to serve as a site of heparin
      binding it is a likely candidate to be involved in the intramolecular interaction
      with the C-terminal region. The interaction of the N- and C-terminal domains of
      arrestin may control the conformational rearrangements in arrestin that occur
      upon binding to P-Rh*.

PMID- 8132603
TI  - Identification of the site of phosphorylation on the osmosensor, EnvZ, of
      Escherichia coli.
AB  - EnvZ is a membrane-bound histidine kinase that functions as an osmotic sensor
      capable of phosphorylating the regulator protein OmpR in Escherichia coli. To
      characterize the site of phosphorylation biochemically, we overexpressed a 36-kDa
      truncated EnvZ protein (Glu-106 to Gly-450) that formed inclusion bodies in the
      cell. After solubilization, the inclusion body form of EnvZ was cleaved into two
      major fragments with molecular weights of 25,000 and 10,000. The 25-kDa fragment,
      EnvZc, was purified and found to exist as a dimer. N-terminal sequence analysis
      established that cleavage had occurred at Arg-214, indicating that EnvZc
      contained most of the cytoplasmic domain of EnvZ. After labeling EnvZc with
      [gamma-32P]ATP, the protein was proteolytically digested, and the resulting
      peptides were separated by reverse phase chromatography using high performance
      liquid chromatography. One major radioactive peptide containing greater than 90%
      of the recovered peptide-associated radioactivity was isolated. Amino acid
      analysis of this purified peptide indicated that the composition was consistent
      with a peptide that contained His-243. The amino acid sequence of this peptide
      was determined to be MAGVSHDLRTP (residues 238-248). These results indicate that
      His-243 is the major site of phosphorylation on EnvZ and represents the first
      biochemical characterization of the site of phosphorylation of a membrane
      histidine kinase of the two-component regulatory family of molecules in bacteria.

PMID- 8132604
TI  - Kinetic and site-directed mutagenesis studies of the cysteine residues of bovine
      low molecular weight phosphotyrosyl protein phosphatase.
AB  - The roles of the 8 conserved cysteines and 1 arginine in the low molecular weight
      phosphotyrosyl protein phosphatases were investigated using site-directed
      mutagenesis of the recombinant bovine heart enzyme. Single mutants of cysteine to
      serine were studied for each cysteine; alanine replacements were also made for
      Cys-12, Cys-17, and Arg-18. The CD spectra of the purified proteins were
      effectively superimposable, consistent with the conclusion that no major
      structural alterations had occurred, but 1H NMR spectroscopy did reveal some
      spectral shifts in the aromatic region. Kinetic analysis of the mutant proteins
      demonstrated that only Cys-12, Cys-17, and Arg-18 had significantly altered
      catalytic activity toward the substrate p-nitrophenyl phosphate at pH 5. The Cys
      12 and Arg-18 mutants were effectively inactive. Thus, it is concluded that Cys
      12 is the catalytic nucleophile, and Arg-18 presumably serves an essential
      function in substrate binding. The C17S mutant had 6% residual activity compared
      with wild type protein, whereas the C17A mutant had 37% activity. Consistent with
      the observed activity of the Cys-17 mutant, a covalent phosphocysteine
      intermediate was trapped and identified by 31P NMR. Further kinetic analysis of
      C17A using several aryl phosphate monoester substrates with different leaving
      group pK alpha values indicated that no change in the rate-determining step of
      the catalytic mechanism had occurred, that is, dephosphorylation of the covalent
      phosphoenzyme intermediate remains rate-limiting. The C17A mutant had a 4-fold
      higher phosphate Ki and slightly higher Km values for p-nitrophenyl phosphate
      suggesting that Cys-17 may be important for optimal positioning of the substrate
      phosphate moiety.

PMID- 8132605
TI  - ATP dependence of NHE-1, the ubiquitous isoform of the Na+/H+ antiporter.
      Analysis of phosphorylation and subcellular localization.
AB  - ATP is not hydrolyzed during the transport cycle of the Na+/H+ exchanger (NHE),
      yet depletion of the nucleotide drastically reduces the rate of cation exchange.
      The mechanism underlying this inhibition was investigated in fibroblasts
      transfected with NHE-1, the growth factor-sensitive isoform of the antiport. NHE
      1 was found to be phosphorylated in serum-starved, unstimulated cells. Acute ATP
      depletion induced a profound inhibition of transport without detectable changes
      in NHE-1 phosphorylation. Analysis of cells transfected with truncated mutants of
      NHE-1 indicated that the carboxyl-terminal cytosolic domain of the antiport is
      required for expression of its ATP dependence. To define whether inhibition of
      Na+/H+ exchange resulted from internalization of NHE-1, extracellularly exposed
      proteins were labeled with impermeant biotin derivatives. The proportion of NHE-1
      exposed to the surface was comparable before and after ATP depletion.
      Immunofluorescence determinations revealed focal accumulations of NHE-1 on the
      membrane of untreated cells. NHE-1 redistributed following ATP depletion, showing
      a more homogeneous localization. F-actin, which co-localizes with the antiport in
      untreated cells, also redistributed when cells were ATP depleted. These findings
      suggest an interaction of NHE-1 with the cytoskeleton. Accordingly, disassembly
      of actin filaments with cytochalasin D induced redistribution of the antiport.
      However, Na+/H+ exchange activity was unaltered by cytochalasin D. We propose
      that ancillary proteins confer ATP sensitivity to the antiporter and may also
      mediate its association with the cytoskeleton. Depletion of the nucleotide would
      alter the interaction between NHE-1 and the putative regulator, inhibiting Na+/H+
      exchange and inducing subcellular redistribution. However, disruption of the
      cytoskeleton at distal sites, such as induced by cytochalasins, is insufficient
      to inactivate the antiport.

PMID- 8132606
TI  - Synchronous oscillations of cytoplasmic Ca2+ and insulin release in glucose
      stimulated pancreatic islets.
AB  - The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured in single pancreatic
      mouse islets superfused in a system allowing concomitant recordings of insulin
      release. When glucose was raised from 3 to 11 mM, [Ca2+]i responded by a
      transient lowering followed by a rise to an average level of 192 +/- 11 nM. In
      77% of the islets the rise was associated with the gradual appearance of
      oscillations, which were either fast (2-7/min), slow (0.3-0.9/min), or a
      combination of both types. The characteristics of the fast [Ca2+]i oscillations
      were those expected from a relationship with the electrical burst activity in
      islets. Accordingly, in most cases the fast oscillations were remarkably regular.
      The slow [Ca2+]i oscillations had characteristics similar to the large amplitude
      ones in individual beta-cells. Whereas glucagon and dibutyryl cAMP could
      transform slow islet oscillations into fast ones, the alpha 2-adrenergic agonist
      clonidine had the opposite effect. The rapid islet oscillations were also
      facilitated by elevated concentrations of extracellular Ca2+. Reinforcing the
      arguments for [Ca2+]i oscillations as responsible for a pulsatile insulin
      secretion it was possible to demonstrate that the release of the hormone from
      single islets is synchronized with the slow [Ca2+]i oscillations.

PMID- 8132607
TI  - The integrin alpha IIb-beta 3, platelet glycoprotein IIb-IIIa, can form a
      functionally active heterodimer complex without the cysteine-rich repeats of the
      beta 3 subunit.
AB  - Integrin alpha IIb-beta 3 binds fibrinogen via the recognition sequence Arg-Gly
      Asp-Ser (RGDS). We have used the baculovirus/insect cell expression system to
      study the structural requirements for the formation of a functionally active
      fragment of alpha IIb-beta 3. A tandem baculovirus transfer vector was
      constructed containing the cDNA coding for the heavy chain of human alpha IIb
      (alpha IIbH, amino acids 1-874) and the cDNA coding for a truncated form of human
      beta 3 (t beta 3; amino acids 1-469). Sf9 insect cells were infected with the
      corresponding baculovirus, and the produced soluble recombinant proteins were
      purified using an RGD-like affinity column. The bound receptor fragments were
      specifically eluted with RGDS and existed as a heterodimeric complex (rec alpha
      IIbH-t beta 3) with an apparent M(r) of 160,000. In an immunocapture assay, the
      monoclonal antibody pl-55, which only recognizes the functionally active form of
      alpha IIb-beta 3, bound to the purified complex. Rec alpha IIbH-t beta 3
      specifically bound 125I-fibrinogen with an affinity comparable with that of
      purified platelet alpha IIb-beta 3. Electron micrographs of rotary-shadowed rec
      alpha IIbH-t beta 3 showed that the complex had the characteristic globular head,
      but the two rodlike tails were 4-6 nm shorter than those found in intact alpha
      IIb-beta 3. Thus, the cysteine-rich repeats of beta 3 are not required for
      assembly, stability, and functional activity of this integrin.

PMID- 8132608
TI  - Structural studies of a novel type of pentaantennary large glycan unit in the
      fertilization-associated carbohydrate-rich glycopeptide isolated from the
      fertilized eggs of Oryzias latipes.
AB  - In a previous report (Kitajima, K., Inoue, S., and Inoue, Y. (1989) Dev. Biol.
      132, 544-553), we found the presence of a heavily glycosylated polyprotein, "H
      hyosophorin," isolated from the unfertilized eggs of Oryzias latipes. We now
      report our detailed analysis of the structure of the N-glycan chain in L
      hyosophorin, the smallest repeating unit of H-hyosophorin, which was isolated
      from the fertilized eggs of O. latipes and formed from H-hyosophorin upon
      fertilization. The N-glycan structures were defined by a combination of
      compositional analysis, methylation analysis, selective chemical degradation
      (i.e. mild methanolysis, periodate-Smith degradation, and hydrazinolysis-nitrous
      acid deamination), enzymatic (endo-beta-galactosidase, peptide:N-glycanase, and
      Newcastle disease virus sialidase) digestion, and instrumental analyses (one- and
      two-dimensional proton nuclear magnetic resonance spectroscopy and fast atom
      bombardment mass spectrometry) which revealed novel and unique features: (a) the
      presence of highly branched poly-N-acetylactosamino pentaantennary structures;
      (b) the presence of a beta-galactosylated Lewis X antigenic epitope, Gal beta 1-
      >4 Gal beta 1-->4 (Fuc alpha 1-->3) GlcNAc beta 1-->; (c) the presence of a beta
      galactosylated sialyl Lewis X structure, Gal beta 1-->4 (Neu5Ac alpha 2-->3) Gal
      beta 1-->4(Fuc alpha 1-->3) GlcNAc beta 1-->; (d) the presence of Gal beta 1-->4
      Gal beta 1--> and Gal beta 1--> 4Gal beta 1-->4Gal beta 1--> as the major and
      minor groupings, respectively; and (e) the presence of the branched Gal residues,
      -->4GlcNAc beta 1-->3(Gal beta 1-->4) Gal beta 1-->. This study represents the
      first detailed investigation regarding the nature of highly branched complex
      asparagine-linked pentaantennary glycans in glycoproteins. The unique expression
      of such bulky multiantennary glycan units on proteins could be essential during
      early embryogenesis.

PMID- 8132609
TI  - Follitropin (FSH) and a phorbol ester stimulate the phosphorylation of the FSH
      receptor in intact cells.
AB  - Using a cell line stably transfected with the rat follitropin (FSH) receptor cDNA
      we demonstrate that the FSH receptor becomes phosphorylated when cells are
      exposed to FSH. Since binding of FSH to its receptor results in an increase in
      cAMP and inositol phosphate accumulation, we examined the potential involvement
      of protein kinase A and C in mediating receptor phosphorylation. Stimulation of
      protein kinase A does not appear to be necessary because hFSH-induced receptor
      phosphorylation was minimally impaired in a cell line that overexpresses cAMP
      phosphodiesterase. Moreover, stimulation of the protein kinase A pathway with
      other agonists result in minimal phosphorylation of the FSH receptor. Stimulation
      of the protein kinase C with a phorbol ester did result in an increase in
      receptor phosphorylation, and down-regulation of the protein kinase C decreased,
      but did not abolish, the FSH-induced receptor phosphorylation. The possible
      impact of phosphorylation on the functions of the receptor was examined by
      testing if conditions that lead to phosphorylation decrease the ability of FSH to
      stimulate cAMP synthesis. Our data show that as with the addition of FSH,
      addition of a phorbol ester also results in a decrease in the ability of FSH to
      stimulate cAMP synthesis.

PMID- 8132610
TI  - Purification and characterization of PTP2C, a widely distributed protein tyrosine
      phosphatase containing two SH2 domains.
AB  - PTP2C, a widely distributed protein tyrosine phosphatase (PTP) containing two SH2
      domains, was expressed as a recombinant enzyme in Escherichia coli and purified
      to near homogeneity. The purified enzyme and a truncated form lacking the SH2
      domains (delta SH2-PTP2C) have been characterized with four commonly used
      substrates. Both forms showed pH optima of around neutrality for protein
      substrates but below 5.5 for a peptide substrate and para-nitrophenylphosphate.
      The dependence of the enzymes on ionic strength varied with the nature of the
      substrates involved. Like its analog PTP1C, PTP2C displayed a specific activity
      of less than 0.1% of that observed with other known PTPs toward protein
      substrates. Deletion of the SH2 domains increased its activity by 12-45-fold,
      depending on the substrates used. Limited trypsinolysis which cleaved about 4 kDa
      from the carboxyl terminus resulted in a 2-5-fold activation of the full-length
      enzyme but was essentially without effect on the truncated enzyme. Both forms
      showed similar responses to effectors including activators (e.g. anionic
      phospholipids) or inhibitors (e.g. vanadate, molybdate, or Zn2+). PTP2C and delta
      SH2-PTP2C were phosphorylated in vitro by mitogen-activated protein kinase,
      protein kinase C, and various protein tyrosine kinases; in the latter case, they
      underwent autodephosphorylation. No significant effect of the phosphorylation
      reactions on enzyme activity could be observed in vitro.

PMID- 8132611
TI  - Early transient suppression of c-myb mRNA levels and induction of differentiation
      in Friend erythroleukemia cells by the [Ca2+]i-increasing agents cyclopiazonic
      acid and thapsigargin.
AB  - Cyclopiazonic acid and thapsigargin, inhibitors of the endoplasmic reticulum Ca2+
      pump were shown to elevate [Ca2+]i in Friend erythroleukemia cells, line F4-6, at
      concentrations of 1-5 microM and 0.5-2 nM, respectively. At the same
      concentrations, these agents induced a strong suppression of c-myb mRNA levels
      within 3 h, whereas c-myc expression remained unaffected. The c-myb expression
      recovered and approached pretreatment levels at 9-12 h of incubation. The
      decrease in c-myb mRNA was prevented in Ca(2+)-free medium. Treatment of F4-6
      cells with EGTA led to a transient increase in c-myb mRNA with the same kinetics
      as the Ca2+ pump inhibitor-induced suppression, indicating that c-myb expression
      is bidirectionally regulated by changes in [Ca2+]i. Studies on the
      differentiation status of F4-6 cells following cyclopiazonic acid or thapsigargin
      exposure demonstrated a marked increase in beta-globin mRNA synthesis at 60h and
      in hemoglobin production at 96 h. These results provide further evidence that a
      rise in the cytosolic Ca2+ concentration is capable, in Friend erythroleukemia
      cells, of inducing an early transient suppression of c-myb mRNA levels, which is
      followed by terminal erythroid differentiation.

PMID- 8132612
TI  - The protein phosphatase calcineurin is essential for NaCl tolerance of
      Saccharomyces cerevisiae.
AB  - NaCl-sensitive yeast mutants were isolated to identify genes essential for NaCl
      tolerance. Complementation of a mutant highly sensitive to Na+ and Li+ led to the
      isolation of the CNB1 gene. This gene encodes the regulatory subunit (CNB) of the
      Ca2+/calmodulin-dependent protein phosphatase calcineurin. Cells deficient in CNB
      accumulated Li+ due to reduced expression of ENA1, a gene encoding a P-type
      ATPase involved in Na+ and Li+ efflux. In addition, the K+ transport system of
      cnb1 delta cells was not converted to the high affinity state that facilitates
      better discrimination of K+ over Na+. Thus the cnb1 delta strain resembled a trk1
      mutant. These results indicate that adaptation to NaCl stress in Saccharomyces
      cerevisiae requires a signal transduction pathway involving Ca2+ and protein
      phosphorylation-dephosphorylation. In this pathway, calcineurin would coordinate
      gene expression and activity of ion transporters to facilitate ion homeostasis.

PMID- 8132613
TI  - A human ubiquitin-conjugating enzyme homologous to yeast UBC8.
AB  - Ubiquitin-conjugating enzymes catalyze the covalent attachment of ubiquitin to
      cellular substrates. Here we describe the isolation of a novel ubiquitin
      conjugating enzyme from human placenta and the cloning of the corresponding cDNA.
      DNA sequencing revealed that this gene, UbcH2, encodes a protein with significant
      sequence similarity to yeast UBC8. In contrast to a previous report (Qin, S.,
      Nakajima, B., Nomura, M., and Arfin, S. M. (1991) J. Biol. Chem. 266, 15549
      15554), we discovered that UBC8 is interrupted by a single intron bearing an
      unusual branch point sequence. The revised amino acid sequence of yeast UBC8
      exhibits 54% amino acid sequence identity to human UbcH2. Moreover, full-length
      UbcH2 and UBC8 enzymes expressed from their cDNAs show similar enzymatic
      activities in vitro by catalyzing the ubiquitination of histones, suggesting that
      the two enzymes may fulfill similar functions in vivo. Interestingly, comparison
      of the enzymatic activities of a truncated UBC8 (Qin, S., Nakajima, B., Nomura,
      M. and Arfin, S. M. (1991) J. Biol. Chem. 266, 15549-15554) and of the full
      length enzyme (this report) suggests, that the first 12 amino-terminal residues
      of UBC8 are required for ubiquitination of histones in vitro but not for
      thiolester formation with ubiquitin. This suggests that the NH2 terminus of UBC8
      may be necessary either for substrate recognition or for the transfer of
      ubiquitin onto substrates. The UbcH2 gene is located on chromosome 7 and shows a
      complex expression pattern with at least five different mRNAs.

PMID- 8132614
TI  - Yonetani-Theorell analysis of hepatic carnitine palmitoyltransferase-I inhibition
      indicates two distinct inhibitory binding sites.
AB  - Analysis of inhibitor studies indicates that carnitine palmitoyltransferase-I has
      two separate sites for inhibitor binding. One site is located on the cytoplasmic
      side of the mitochondrial outer membrane. Malonyl-CoA, the most important
      physiological inhibitor of carnitine palmitoyltransferase-I, binds primarily to
      this site, but it can also bind to another site. A second inhibitory site is
      located at the active site of carnitine palmitolytransferase-I. Coenzyme A, a
      product/inhibitor of carnitine palmitoyltransferase-I binds primarily at this
      site and can inhibit carnitine palmitoyltransferase-I at physiological
      concentrations, but can also attenuate malonyl-CoA inhibition. Analogs of malonyl
      CoA and other simpler compounds containing two carbonyl groups but no coenzyme A
      moiety inhibit only at the cytoplasmic site, indicating that this site has an
      absolute requirement for two carbonyl groups but has no absolute requirement for
      a coenzyme A moiety. Inhibitors acting through the active site included the
      active-site-directed inhibitor (+)-hemipalmitoylcarnitinium. These studies
      support the existence of two regulatory binding sites for the control of hepatic
      fatty acid oxidation: (a) the active site, for regulation by the inhibitory
      binding of coenzyme A and acetyl-CoA, and (b) a separate regulatory malonyl-CoA
      binding site that is physical separated from the active site.

PMID- 8132615
TI  - Conserved tyrosines in the alpha subunit of the nicotinic acetylcholine receptor
      stabilize quaternary ammonium groups of agonists and curariform antagonists.
AB  - Studies with site-directed labeling reagents have identified residues near the
      ligand binding pocket of the nicotinic acetylcholine receptor. Among these
      residues are three conserved tyrosines, Tyr-93, Tyr-190, and Tyr-198 of the alpha
      subunit. Previous studies combined mutagenesis, expression in Xenopus oocytes,
      and dose-response analysis to examine contributions of these tyrosines to agonist
      affinity. In this study, we prepared a series of mutants at each position,
      expressed them in 293 HEK cells, and studied binding of agonists and antagonists
      to mutant receptors on intact cells. We show that all three tyrosines contribute
      to binding of agonists, and that each tyrosine contributes roughly equally to the
      binding energy. Although the contributions are roughly equivalent, the nature of
      the contribution is not equivalent at each position. For Tyr-93 and Tyr-190 the
      aromatic hydroxyl is essential, whereas for Tyr-198 aromaticity of the side chain
      is essential. Nearly identical results were obtained for the elementary
      quaternary ligand tetramethylammonium, indicating that these tyrosines contribute
      to stabilization of the quaternary ammonium portion of agonist. Tyr-190 and Tyr
      198 also contribute to binding of the competitive antagonist dimethyl-d
      tubocurarine; the side chain specificity for binding supports tyrosine
      interactions with one of two quaternary ammonium groups in dimethyl-d
      tubocurarine. Y190F, in addition to altering binding affinity, also affects the
      equilibrium between activatable and desensitized receptor states.

PMID- 8132616
TI  - Association of Raf with the CD3 delta and gamma chains of the T cell receptor-CD3
      complex.
AB  - Protein kinases and phosphatases play an important role in signal transduction.
      In the T cell, activation via the T cell receptor-CD3 complex results in rapid
      tyrosine phosphorylation of proteins, as well as subsequent increases in
      serine/threonine phosphorylation. The Raf serine/threonine kinase has been
      implicated in many receptor signaling pathways, including those of platelet
      derived growth factor, epidermal growth factor, insulin, and interleukin-2
      receptors. We show here that Raf is associated with the T cell receptor-CD3
      complex in unstimulated murine T cells. Using a COS cell expression system, we
      show that a hypophosphorylated form of Raf specifically associates with the CD3
      gamma and delta chains but not with the CD3 epsilon or zeta chains. These results
      suggest that Raf mediates signal transduction from the gamma and delta chains of
      the T cell receptor-CD3 complex, analogous to the role played by ZAP-70 in signal
      transduction mediated by the zeta chain.

PMID- 8132617
TI  - Reaction of rat liver glutathione S-transferases and bacterial dichloromethane
      dehalogenase with dihalomethanes.
AB  - Dichloromethane dehalogenase from Methylophilus sp. DM11 is a glutathione S
      transferase homolog that is specifically active with dihalomethane substrates.
      This bacterial enzyme and rat liver glutathione S-transferases were purified to
      investigate their relative reactivity with CH2Cl2 and related substrates. Rat
      liver alpha class glutathione transferases were inactive and mu class enzymes
      showed low activity (7-23 nmol/min/mg of protein) with CH2Cl2. theta class
      glutathione transferase 5-5 from rat liver and Methylophilus sp. dichloromethane
      dehalogenase showed specific activities of > or = 1 mumol/min/mg of protein.
      Apparent Kcat/Km were determined to be 3.3 x 10(4) and 6.0 x 10(4) L M-1 S-1 for
      the two enzymes, respectively. Dideutero-dichloromethane was processed to
      dideutereo-formaldehyde, consistent with a nucleophilic halide displacement
      mechanism. The possibility of a GSCH2X reaction intermediate (GS, glutathione; X,
      halide) was probed using CH2ClF to generate a more stable halomethylglutathione
      species (GSCH2F). The reaction of CH2ClF with dichloromethane dehalogenase
      produced a kinetically identifiable intermediate that decomposed to formaldehyde
      at a similar rate to synthetic HOCH2CH2SCH2F. 19F-NMR revealed the transient
      formation of an intermediate identified as GSCH2F by its chemical shift, its
      triplet resonance, and H-F coupling constant consistent with a
      fluoromethylthioether. Its decomposition was matched by a stoichiometric
      formation of fluoride. These studies indicated that the bacterial dichloromethane
      dehalogenase directs a nucleophilic attack of glutathione on CH2Cl2 to produce a
      halomethylthioether intermediate. This focuses attention on the mechanism used by
      theta class glutathione transferases to generate a halomethylthioeter from
      relatively unreactive dihalomethanes.

PMID- 8132618
TI  - Systematic mutagenesis of the yeast mating pheromone receptor third intracellular
      loop.
AB  - Signal transduction in the mating pathway of the yeast Saccharomyces cerevisiae
      is initiated by binding of a peptide pheromone to a G protein-coupled receptor
      (Ste2). We systematically have mutated the third intracellular loop of the Ste2
      receptor to investigate its functional significance. We substituted each of the
      13 amino acids in the loop with alanine individually or together with one other
      residue. In addition, we used a site-directed random replacement mutagenesis
      technique to replace a region encoding three amino acids in the loop with random
      sequence. Over 80 such Ste2 mutants have been analyzed by several functional and
      biochemical criteria in a yeast strain that carries a genomic deletion of the
      STE2 gene. The mutant phenotypes range from fully functional to severely
      compromised in signaling. The observation that amino acid substitutions in the
      third intracellular loop of the Ste2 receptor can affect activation of the yeast
      mating response implicates the loop in this signal transduction pathway. The
      types of mutations that compromise the function of the receptor may provide clues
      to the physical interaction between the receptor and the G protein.

PMID- 8132619
TI  - Y2 receptors for neuropeptide Y are coupled to three intracellular signal
      transduction pathways in a human neuroblastoma cell line.
AB  - Neuropeptide Y (NPY) attenuated angiotensin II (AII)-or bradykinin (BK)-induced
      Ca2+ release from intracellular stores and inhibited forskolin-stimulated cAMP
      accumulation and omega-conotoxin-sensitive high K(+)-induced Ca2+ influx in the
      human neuroblastoma cell line SMS-KAN. All three NPY actions were mediated via Y2
      receptors. Pretreatment with pertussis toxin completely abolished all of the NPY
      actions. Activation or down-regulation of protein kinase C had no effect on any
      NPY-mediated effect; herbimycin A, a tyrosine kinase inhibitor, only abolished
      the inhibitory effect of NPY on AII- or BK-induced Ca2+ mobilization. Herbimycin
      A also blocked platelet-derived growth factor-induced Ca2+ mobilization, which
      involves tyrosine kinase activation, and there was a good correlation in the
      concentration dependency between the two effects of herbimycin A, strongly
      suggesting that its ability to cancel the NPY effect is due to inhibition of
      tyrosine kinase activity. NPY attenuated AII- or BK-induced inositol 1,4,5
      trisphosphate production, and herbimycin A reversed this NPY effect. These
      results provide the first evidence that Y2 receptors negatively couple to AII- or
      BK-induced phosphoinositide turnover leading to Ca2+ mobilization through
      pertussis toxin-sensitive GTP-binding protein(s). Inhibition of phospholipase C
      beta activity by NPY seems to be mediated by activation of protein-tyrosine
      kinase or phosphotyrosine-containing protein(s).

PMID- 8132620
TI  - Regulation by glucagon of serine: pyruvate/alanine: glyoxylate aminotransferase
      gene expression in cultured rat hepatocytes.
AB  - The effects of glucagon on serine: pyruvate/alanine: glyoxylate aminotransferase
      (SPT/AGT) gene expression were studied in primary cultured rat hepatocytes. When
      hepatocytes had been precultured for 16-18 h under serum- and hormone-free
      conditions, the addition of glucagon caused (after a lag period of about 2 h) a
      remarkable increase in the cellular level of SPT/AGT mRNA by 4 h in a time- and
      dose-dependent manner. The induced mRNA was that for mitochondrial SPT/AGT, as
      judged by ribonuclease protection analysis. A nuclear run-on assay revealed that
      activation of transcription is responsible for the increase in mitochondrial
      SPT/AGT mRNA and that the maximal rate of transcription occurs 1.5 h after
      glucagon addition. The effect of glucagon was mimicked by 8-bromo-cAMP and
      suppressed by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, an
      inhibitor of cAMP-dependent protein kinase (protein kinase A), while both 12-O
      tetradecanoylphorbol-13-acetate and A23187 were without effect in elevating the
      SPT/AGT mRNA level, suggesting that the cAMP/protein kinase A system is involved
      in the regulation of SPT/AGT gene expression. In hepatocytes precultured for 16
      18 h under serum- and hormone-free conditions, the glucagon-induced transcription
      was severely inhibited by cycloheximide. When the preculture was for 2 h, on the
      other hand, the activation of transcription by glucagon was more rapid, and the
      inhibition by cycloheximide was less than that observed with cells precultured
      for 16-18 h, suggesting that a short-lived protein factor is involved in the
      hormonal regulation. The glucagon-induced expression of the SPT/AGT gene was also
      turned off by dexamethasone.

PMID- 8132621
TI  - Negative regulation of hepatitis B virus gene expression and replication by
      oxidative stress.
AB  - We present data demonstrating that hydrogen peroxide markedly decreases release
      of progeny hepatitis B virus particles in cultured cells. The presence of reduced
      glutathione prevents this effect. Hydrogen peroxide also decreases secretion of
      the hepatitis B virus surface and e antigens, with a concomitant decrease in the
      steady-state levels of the corresponding viral transcripts. This effect is
      specific to viral gene expression, since hydrogen peroxide at the concentration
      used does not have any significant effect on the overall pattern of host cell
      protein synthesis nor on the secretion of growth hormone from a co-transfected
      plasmid. Since hepatitis B virus can cause acute and chronic hepatitis and since
      inflammatory cells release significant amounts of reactive oxygen species,
      including hydrogen peroxide, this phenomenon may be of pathophysiological
      importance in the viral life cycle.

PMID- 8132622
TI  - Homodimer and heterodimer DNA binding and transcriptional responsiveness to
      triiodothyronine (T3) and 9-cis-retinoic acid are determined by the number and
      order of high affinity half-sites in a T3 response element.
AB  - T3 (triiodothyronine) response elements (TREs) consist of pairs of strong and
      weak (S and W), 10-nucleotide T3 receptor (TR) monomer binding sites (half
      sites). We report that the number and order of S and W half-sites in a direct
      repeat TRE determines whether it mediates ligand-dependent or independent
      transcriptional activation or inhibition in the presence of TR or TR and 9-cis
      retinoic acid receptor (RXR); and whether a TRE is preferentially bound by TR
      homodimers, TR-RXR heterodimers, or CV1 cell TR accessory protein (TRAP)-TR
      heterodimers. TR homodimers bound equally to TREs composed of the 5'-S and 3'-W
      (SW) and the opposite (WS) arrangement of half-sites. TR-RXR gamma heterodimers
      bound SW better than WS. TR-TRAP heterodimers bound WS better than SW.
      Transcription of a reporter gene cis-linked to WS responded to unliganded TR and
      RXR, and either ligand stimulated expression 2-fold more. Reporter expression cis
      linked to SW was not altered by unliganded receptors, and T3 stimulated
      transcription only in the presence of both TR and RXR. SS was strongly activated
      by liganded, but not by unliganded TR. SS was activated by unliganded TR and RXR
      gamma together, and T3 further stimulated transcription 2-fold. Under these
      conditions, transcription was inhibited 60% by 9-cis-retinoic acid.

PMID- 8132623
TI  - Glucocorticoid inhibition of Na-Pi cotransport in renal epithelial cells is
      mediated by protein kinase C.
AB  - The effect and mechanism of action of glucocorticoids (GC) on Na-Pi cotransport
      were evaluated in opossum kidney cells. Dexamethasone (1-1000 nM) inhibited
      sodium-dependent Pi uptake in a time- and concentration-dependent manner.
      Inhibition was maximal after a 6-h incubation with dexamethasone and was
      prevented by cycloheximide and actinomycin D. The effect was related to a 37%
      decrease of the Vmax value after incubation with 100 nM dexamethasone. The effect
      of dexamethasone was mimicked by cortisol and blocked by GC receptor antagonists
      RU38486 and progesterone. GC affected neither glucose or alanine uptake nor Na/H
      exchange activity. Inhibition of Pi uptake persisted when Na/H was blocked by
      amiloride or dimethylamiloride. GC had no effect on basal or parathyroid hormone-
      and forskolin-stimulated intracellular cAMP content. Dexamethasone and
      extracellular cAMP, parathyroid hormone, or 3-isobutyl-1-methylxanthine had
      additive inhibitory effects on Pi uptake. Staurosporine, GF109203X, or calphostin
      C (three dissimilar inhibitors of protein kinase C (PKC)) and PKC down-regulation
      blunted the inhibitory effect of glucocorticoids on Pi uptake. GC increased both
      membrane-bound PKC activity and the membrane/cytosol PKC activity ratio. This is
      the first report of GC activation of PKC in renal cells, which appears to mediate
      the steroid inhibitory effect on Pi transport.

PMID- 8132624
TI  - Physical and functional association of Src-related protein tyrosine kinases with
      Fc gamma RII in monocytic THP-1 cells.
AB  - Aggregation of Fc gamma RII (CD 32), a low affinity receptor for immunoglobulin G
      (IgG), on the monocytic cell line THP-1 induces protein tyrosine kinase (PTK)
      activity. Several distinct cellular proteins, including Fc gamma RII itself, are
      phosphorylated on tyrosine following cross-linking of the receptor. Fc gamma RII
      lacks intrinsic PTK activity. In this report we demonstrate that a kinase
      activity was coprecipitated with Fc gamma RII in THP-1 cells. The kinetics of the
      receptor-associated kinase activity paralleled the appearance of tyrosine
      phosphorylation events observed following Fc gamma RII activation of THP-1 cells.
      Several proteins were associated with the receptor. Reimmunoprecipitation
      analysis demonstrated that lyn gene products were among the proteins
      coprecipitated with Fc gamma RII. p59hck (Hck) and p56lyn (Lyn) were the most
      abundant Src-related PTKs (Src-PTKs) in THP-1 cells. Enzymatic activity of both
      kinases, as measured by an in vitro kinase assay, was increased following
      specific cross-linking of Fc gamma RII. Furthermore, Fc gamma RII was
      specifically associated with both enzymes following its engagement and served as
      a substrate for both of these kinases. The association of Fc gamma RII with Src
      PTK was specific for Fc gamma RII activation of THP-1 cells, since activation of
      cells via the high affinity Fc gamma receptor, Fc gamma RI (CD 64), did not
      result in association of Fc gamma RII with Hck or Lyn. Our data demonstrate a
      functional and physical association of Fc gamma RII with Hck and Lyn consistent
      with the involvement of Src-PTK in Fc gamma RII-mediated signal transduction.

PMID- 8132625
TI  - Irreversible inhibition of nicotinic acetylcholine receptors by the bipinnatins.
      Toxin activation and kinetics of receptor inhibition.
AB  - Bipinnatin-A, -B, and -C belong to a family of naturally occurring marine
      neurotoxins known as the lophotoxins. The lophotoxins are unique in that they
      irreversibly inhibit nicotinic acetylcholine receptors by forming a covalent bond
      with a tyrosine residue at position 190 in the alpha-subunit of the receptor. In
      this study, we show that the inhibitory activity of the bipinnatins against the
      nicotinic receptor increased with preincubation of the toxins in aqueous buffer
      prior to incubation with the receptor. The parent species of the bipinnatins
      displayed little, if any, affinity for the nicotinic receptor. Preincubation of
      the toxins appeared to produce a single, relatively stable, active toxin species
      that irreversibly inhibited the two acetylcholine-binding sites on the nicotinic
      receptor with two distinguishable apparent pseudo first-order rates. The
      difference in the rates of irreversible inhibition of the two binding sites on
      the receptor was exploited to selectively inhibit one site for the
      pharmacological investigation of the other. The bipinnatins preferentially
      inhibited the binding site near the alpha/delta-subunit interface that displays
      low affinity for metocurine and high affinity for acetylcholine. The bimolecular
      reaction constants for the interaction of the bipinnatins with the nicotinic
      receptor decreased in the order bipinnatin-B > bipinnatin-A > bipinnatin-C for
      both acetylcholine-binding sites. The ratio of the bimolecular reaction constants
      for the two binding sites on the receptor was not the same for the three
      bipinnatins. This indicates that the reaction of the bipinnatins with the
      nicotinic receptor is sensitive to differences in the structure of the two
      acetylcholine-binding sites. The bipinnatins may be useful in the design of novel
      drugs for the nicotinic receptor that exclusively inhibit one of the two binding
      sites and for the investigation of structural differences between the two
      acetylcholine-binding sites of the receptor.

PMID- 8132626
TI  - Transcriptional regulation of the human Wilms' tumor gene (WT1). Cell type
      specific enhancer and promiscuous promoter.
AB  - The Wilms' tumor gene, WT1, is expressed in few tissues, mainly the developing
      kidney, genitourinary system, and mesothelium, and in immature hematopoietic
      cells. To develop an understanding of the role of WT1 in development and
      tumorigenesis, we have identified transcriptional regulatory elements that
      function in transient reporter gene constructs transfected into kidney and
      hematopoietic cell lines. We found three transcription start sites of the WT1
      gene and have identified an essential promoter region by deletion analysis. The
      WT1 promoter is a member of the GC-rich, TATA-less, and CCAAT-less class of
      polymerase II promoters. Whereas the WT1 promoter is similar to other tumor
      suppressor gene promoters, the WT1 expression pattern (unlike Rb and p53) is
      tissue-restricted. The WT1 GC-rich promoter is promiscuous, functioning in all
      cell lines tested, independent of WT1 expression. This finding suggests that the
      promoter is not tissue-specific, but that tissue-specific expression of WT1 is
      modulated by additional regulatory elements. Indeed, we have identified a
      transcriptional enhancer located 3' of the WT1 gene > 50 kilobases downstream
      from the promoter. This orientation-independent enhancer increases the basal
      transcription rate of the WT1 promoter in the human erythroleukemia cell line
      K562, but not in any of the other cell lines tested.

PMID- 8132627
TI  - Studies on the function of yeast phosphofructokinase subunits by in vitro
      mutagenesis.
AB  - Genetic and biochemical analysis of phosphofructokinase in the yeast
      Saccharomyces cerevisiae led to contradictory hypotheses about the function of
      the subunits of this heterooctameric enzyme. To gain further insight, we
      exchanged four evolutionary conserved amino acid residues in each of the two
      yeast subunits affecting presumed catalytic and regulatory functions. In
      conjunction with a complementary wild-type subunit, each of the mutant subunits
      led to a loss of a maximum of 50% of phosphofructokinase activity as compared to
      wild-type cells. Km values for fructose 6-phosphate were increased in most of
      these mutants. None of the mutant subunits lacking catalytical functions was able
      to complement the glucose-negative phenotype of a yeast pfk1 pfk2 double mutant
      when expressed from a single-copy vector. For the beta-subunits, the other
      mutants did complement, whereas for the alpha-subunits they did not.
      Concentrations of fructose 1,6-bisphosphate did not drastically change in
      metabolite determinations in strains carrying one mutant allele, suggesting that
      the effect of the mutations introduced can be largely compensated by in vivo
      regulatory mechanisms, as long as one functional subunit is present. The data
      implicate that each of the yeast phosphofructokinase subunits can serve
      catalytically as well as regulatory functions.

PMID- 8132628
TI  - Modulation of Ca2+ exchange with the Ca(2+)-specific regulatory sites of troponin
      C.
AB  - Calcium (Ca2+) binding to the N-terminal Ca(2+)-specific sites on troponin C
      (TnC) regulate the contraction-relaxation cycle of skeletal muscle. A mutant TnC
      (F29W) and dansylaziridine-labeled TnC undergo large fluorescence increases when
      Ca2+ binds to their Ca(2+)-specific sites (half-maximal at pCa 5.8).
      Calmidazolium and the additional mutation of Met-82 to Gln (F29W,M82Q) increased
      Ca2+ affinity at these Ca2+ sites by approximately 4-fold (half-maximal at pCa
      approximately 6.4). Calmidazolium and the M82Q mutation decreased the rate of
      Ca2+ dissociation from the Ca(2+)-specific sites approximately 3.4-fold (from
      approximately 462 +/- 84/s to approximately 138 +/- 30/s) at 22 degrees C. Ca2+
      associated with the Ca(2+)-specific sites of these proteins at 1-2 x 10(8) M-1 s
      1 at 4 degrees C. These drug- and mutation-induced increases in Ca2+ affinity
      occur solely from large decreases in the Ca2+ off-rate without an effect on the
      Ca2+ on-rate. Thus, Ca2+ can bind to the Ca(2+)-specific sites of TnC as rapidly
      as it can diffuse to the protein, consistent with the extreme speed of skeletal
      muscle contraction. Drugs and/or site-directed mutagenesis can modify the Ca2+
      sensitivity and the rate of Ca2+ exchange with TnC's Ca(2+)-specific sites to
      perhaps alter the rate of relaxation and/or the rate of rise of tension.

PMID- 8132629
TI  - Mechanisms of assembly of wheat high molecular weight glutenins inferred from
      expression of wild-type and mutant subunits in transgenic tobacco.
AB  - Following sequestration into the endoplasmic reticulum, wheat high molecular
      weight glutenin subunits (HMW-GS) assemble into polymers through intermolecular
      disulfide bond formation. These polymers, which also include low molecular weight
      glutenin subunits (LMW-GS), have a broad distribution of molecular mass reaching
      up to several million daltons. To study the mechanism of assembly of the HMW-GS,
      we have expressed x- and y-type HMW-GS in transgenic tobacco plants. Both types,
      when expressed individually or in combination, were incorporated into polymers.
      Partial reduction of polymers formed by different subunits resulted in different
      patterns of release of homodimers, heterodimers, and monomers. This suggested
      different arrangements of intermolecular disulfide bonds or different peptide
      conformations in the vicinity of the disulfide bonds linking x-x, y-y, and x-y
      type HMW-GS. A mutant of the x-type subunit, lacking a conserved cysteine in the
      C-terminal domain, assembled into oligomers linked by intermolecular disulfide
      bonds, but not into large polymers. This mutant was deposited, however, in dense
      protein bodies, similar to those formed by the native HMW-GS, suggesting that
      polymer formation and packaging into protein bodies may be the result of
      different types of interactions. Pulse-chase labeling of proteins in wheat
      endosperm showed that the assembly of the HMW-GS into insoluble polymers occurs
      by a slow process which apparently continues after the initiation of protein body
      formation.

PMID- 8132630
TI  - The 1.9 A x-ray structure of a closed unliganded form of the periplasmic
      glucose/galactose receptor from Salmonella typhimurium.
AB  - The three-dimensional structure of a ligand-free closed form of the
      glucose/galactose binding protein from Salmonella typhimurium has been determined
      at a resolution of 1.9 A. The crystallographic R-factor for the refined structure
      is 17.9%. The model contains all the atoms of the 309 residues of the protein
      sequence, a calcium ion, and 174 water molecules. The root mean square (r.m.s.)
      deviations for the whole molecule are: 0.010 A for bond lengths and 2.44 degrees
      for bond angles, indicating a good stereochemistry for the model. This structure
      shows that the protein is able to close in the absence of ligand, adopting a
      conformation similar to the liganded form but slightly more open. Water molecules
      satisfy the hydrogen bonding ability of the hydrophilic side chains of the
      binding site in a manner which is reminiscent of the sugars' hydrogen-bonding
      patterns. Since packing forces are weak, the crystallization event is unlikely to
      trigger a change from an open to a closed conformation. Instead, the latter must
      be one of the species in equilibrium in solution which is selected by packing in
      the crystal lattice.

PMID- 8132631
TI  - Cell-permeable ceramides inhibit the stimulation of DNA synthesis and
      phospholipase D activity by phosphatidate and lysophosphatidate in rat
      fibroblasts.
AB  - The interactions of ceramides with phosphatidate and lysophosphatidate in the
      regulation of signal transduction in rat fibroblasts were examined. C2- and C6
      ceramides (N-acetylsphingosine and N-hexanoylsphingosine, respectively) at 10
      microM inhibited the stimulation of DNA synthesis that was produced by 50-100
      microM phosphatidate, or lysophosphatidate, or by exogenous phospholipase D.
      Sphingosine (10 microM) had the opposite effect to the ceramides on DNA
      synthesis. C2- or C6-ceramides failed to inhibit the stimulation of DNA synthesis
      by insulin or serum. The ceramides did not modify the actions of phosphatidate,
      or lysophosphatidate, in decreasing the forskolin-induced increase in cAMP. C2-
      and C6-ceramides inhibited the stimulation of phospholipase D activity by: (a)
      phosphatidate, lysophosphatidate, phorbol ester, thrombin, or serum in intact
      fibroblasts and (b) phorbol ester or guanosine 5'-3-O-(thio)triphosphate in
      permeabilized fibroblasts. The ceramides can therefore modify cell signaling via
      phospholipase D, but this effect alone could not explain the decreased DNA
      synthesis. Incubation of fibroblasts with C2- or C6-ceramides or sphingomyelinase
      inhibited the interaction of exogenous phosphatidate or lysophosphatidate with
      the fibroblasts by 42 and 53%, respectively. Furthermore, a greater proportion of
      the phosphatidate, or lysophosphatidate, that was associated with the fibroblasts
      was metabolized further when the cells were pretreated with ceramides or
      sphingomyelinase. This effect was accompanied by an increased activity of N
      ethylmaleimide-insensitive phosphatidate phosphohydrolase. Ceramides may
      therefore produce part of their growth inhibitory effects by blocking some of the
      signal transducing effects of phosphatidate and lysophosphatidate.

PMID- 8132632
TI  - Expression of the L-type pyruvate kinase gene and the hepatocyte nuclear factor 4
      transcription factor in exocrine and endocrine pancreas.
AB  - The L-pyruvate kinase (L-PK) gene is slightly active in normal and tumoral
      endocrine pancreatic tissues while, in vivo, this gene is not transcribed in the
      exocrine pancreas. Nevertheless, the L-PK gene is re-expressed at a very low
      level in cultured 266.6 cells derived from an exocrine pancreas carcinoma. The L
      PK gene is early activated in endodermal tissues, e.g. yolk sac and primitive
      intestine; it remains transcribed in fetal pancreas. In adult, L-PK gene
      expression is restricted to some endocrine cells. Hepatocyte nuclear factor (HNF)
      1 and HNF4 are the main tissue-restricted transcription factors involved in
      tissue-specific expression of the L-PK gene. HNF1 concentration is similar in
      liver and all pancreatic cells. HNF4 concentration is high in liver, much lower
      in islets of Langerhans, endocrine pancreatic tumors, and cultured insulinoma
      cells, and is scarcely detectable in adult exocrine pancreas. This distribution
      of HNF4 parallels the expression of the L-PK gene. In vivo footprinting
      experiments show that the HNF1 binding site is similarly occupied in both adult
      liver and adult pancreas, in which this gene is practically inactive. In this
      latter tissue, however, the HNF4 binding site is differently occupied with
      respect to the liver. Since the chromatin structure remains open around the L-PK
      promoter in pancreas, the L-PK gene can probably be re-expressed under certain
      circumstances, for instance in cancerous pancreatic cells.

PMID- 8132633
TI  - The molecular basis for the difference in charge between pre-beta- and alpha
      migrating high density lipoproteins.
AB  - Several subspecies of human high density lipoprotein (HDL) exist, and particle
      surface charge is one parameter that can be used to distinguish them. For
      instance, pre-beta HDL has a lower negative surface charge than the bulk of
      plasma HDL resulting in slower migration when subjected to electrophoresis in an
      agarose gel at pH 8.6. The molecular basis for the variations in HDL particle
      surface charge have been established in this work. Quantitative analysis of
      electrophoretic mobilities in agarose gels indicates that the surface potentials
      of reconstituted pre-beta HDL and alpha-HDL3 are -7.6 and -11.4 mV, respectively.
      The difference of 3.8 mV corresponds to an apparent 1e more net negative charge
      on alpha-migrating HDL3. The contributions of the lipid and protein components to
      the charge of HDL3 were defined using reconstituted particles (rHDL) containing
      various combinations of HDL3 protein and lipid. The surface potentials of
      spherical and discoidal rHDL are not affected by the particle apoprotein
      composition. Thin layer chromatography of the HDL3 phospholipid fraction from
      five normolipidemic subjects revealed that it consists of approximately 84%
      phosphatidylcholine, 12% sphingomyelin, and 4% phosphatidylinositol (PI) by
      weight. PI significantly affects the charge of discoidal rHDL and is responsible
      for approximately 0.7 mV of the surface potential difference between pre-beta-
      and alpha-HDL. Reconstitution of spherical complexes containing apolipoprotein
      AI, palmitoyl-oleoyl phosphatidylcholine, and HDL3 neutral lipid esters showed
      that particles containing a neutral lipid core migrate to an alpha position in an
      agarose gel. The change in particle shape accounts for approximately 3 mV of the
      difference in surface potential between pre-beta and alpha-HDL. Overall, the
      charge of HDL particles is determined by 1) a direct contribution of negative
      charge from PI molecules in the surface of the lipoprotein and 2) the
      conformation of the resident apolipoprotein(s) which is influenced by the
      presence of neutral lipids and the particle shape. This quantitative
      understanding of surface charge provides a basis for understanding variations in
      function of HDL subspecies.

PMID- 8132634
TI  - Proteolytic activation of hepatocyte growth factor in response to tissue injury.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and renal
      tubular epithelial cells and may play an important role in regeneration following
      hepatic and renal injury. HGF is first synthesized as a single chain precursor
      which is then converted to a heterodimeric form by proteolytic processing. This
      proteolytic conversion is required for HGF to function as a mitogen. In this
      study, we examined whether the proteolytic activation of HGF occurred in response
      to hepatic and renal injury. HGF remained as an inactive single chain form in the
      liver, kidney, lung, and spleen of normal rats. The production of HGF markedly
      increased in the liver after hepatotoxin treatment and in the kidney after
      nephrotoxin treatment. A significant portion of the increased HGF was converted
      to the active heterodimeric form, whereas in other tissues, conversion did not
      occur although the production of HGF increased in some of them. Furthermore, an
      enzymatic activity that converts the single chain form of HGF to the active
      heterodimeric form was detected in the injured liver but not in the normal liver.
      These results indicate that HGF is proteolytically activated in response to
      tissue injury, and this activation is mediated by an enzymatic activity which is
      induced exclusively in the injured tissues. Thus, the proteolytic activation
      system functions in vivo as a mechanism for localizing HGF activities to injured
      tissues.

PMID- 8132635
TI  - Heterologous expression of human prostatic acid phosphatase and site-directed
      mutagenesis of the enzyme active site.
AB  - Earlier covalent modification experiments indicated that histidine, arginine, and
      carboxylic acid residues were involved in the catalytic mechanism of the acid
      phosphatase enzyme from human prostate. The present study utilizes site-directed
      mutagenesis to evaluate the catalytic importance of 7 residues of human prostatic
      phosphatase, namely His12, His257, Asp258, Arg11, Arg15, Arg54, and Arg79, which
      are highly conserved in the sequences of high molecular weight acid phosphatases.
      Both wild type and mutant enzymes were expressed in the yeast Saccharomyces
      cerevisiae as fusions to a leader peptide of prepro-alpha-factor, which resulted
      in the secretion of processed proteins into the culture media. The kinetic
      parameters of the recombinant wild type enzyme were shown to be effectively
      identical with those of the native protein. The circular dichroism spectra of
      wild type and mutant proteins were effectively superimposable. Replacement of
      His12, which was previously shown to be transiently phosphorylated during
      catalysis, as well as the adjacent Arg11, both resulted in > 10(4) reductions of
      enzyme activity. Consistent with a postulated involvement of arginine residues in
      substrate binding, large reductions in Vmax caused by the R15A and R79A mutations
      were accompanied by marked increases in Km. However, the mutation R54A had only
      small effects on kinetic parameters. Essential roles for both His257 and Asp258
      were also established. The D258A mutation not only caused larger decreases of
      Vmax toward p-nitrophenyl phosphate compared to the effect of the H257A mutation,
      but it also caused the reaction to become more sensitive to the nature of the
      leaving group. It is concluded that His12 and Asp258 are involved in the
      formation of the phosphoenzyme intermediate as an acceptor of the phospho group
      and a proton donor for the substrate leaving group, respectively, while His257
      may participate in substrate binding or may facilitate the breakdown of the
      phosphoenzyme by maintaining the protonated state of the phosphorylated His12
      residue.

PMID- 8132636
TI  - A carboxyl-terminal four-amino acid motif is required for secretion of the
      metalloprotease PrtG through the Erwinia chrysanthemi protease secretion pathway.
AB  - PrtG is an extracellular metalloprotease secreted by the Gram-negative bacterium
      Erwinia chrysanthemi through a signal peptide-independent secretion pathway.
      Previous studies showed that the PrtG secretion signal is COOH-terminal and
      located in the last 56 residues of PrtG. We have now performed a deletion and
      elongation mapping of a short secretion competent COOH-terminal peptide CterG.
      This approach allowed us to show that: (i) the smaller COOH-terminal sequence
      containing the information necessary to promote the secretion of a small
      polypeptide is contained in the last 29 residues of PrtG; (ii) a low but
      significant level of secretion can be promoted by the last 15 residues of PrtG
      when fused to the COOH terminus of a non-secreted PrtG derivative; (iii) the
      extreme COOH-terminal sequence Dxxx, where xs are hydrophobic residues, is a
      conserved motif in all constructs that are secreted through the E. chrysanthemi
      transporter. (vi) This motif has to be COOH terminally exposed since addition of
      even one amino acid impairs the secretion of CterG. The extent of the secretion
      defect observed with the COOH terminally extended variants correlates with the
      length of the extension. These results indicate a key role for the COOH-terminal
      exposition of the last four amino acids in the secretion of PrtG.

PMID- 8132637
TI  - Post-transcriptional regulation of glutamyl-prolyl-tRNA synthetase in rat
      salivary gland.
AB  - Treatment of rats with isoproterenol resulted in elevated levels of prolyl- and
      glutamyl-tRNA synthetase activities in the parotid and submandibular glands. This
      increase in enzyme activity was accompanied by an increase in the bi-functional
      glutamyl-prolyl-tRNA synthetase and of a low molecular weight form of prolyl-tRNA
      synthetase. Isoproterenol also induced the synthesis of proline-rich
      glycoproteins in the parotid and submandibular glands. Withdrawal from the drug
      was accompanied by a decline in prolyl- and glutamyl-tRNA synthetase activities
      and by a decline in the levels of proline-rich glycoproteins in the salivary
      gland. During the time course of isoproterenol treatment, little change in the
      levels of mRNA encoding the bi-functional glutamyl-prolyl-tRNA synthetase was
      detected by Northern blot analysis. These results indicate that the synthesis of
      glutamyl-prolyl-tRNA synthetase is regulated at a post-transcriptional step and
      that the synthesis of this bifunctional protein may be linked to the utilization
      of proline and glutamic acid in protein synthesis.

PMID- 8132638
TI  - Altering the RNA binding specificity of a translational repressor.
AB  - The coat proteins of RNA phages MS2 and GA are specific RNA-binding proteins
      which function to encapsidate viral RNA and to translationally repress synthesis
      of the viral replicase. The two proteins have highly homologous amino acid
      sequences, yet they show different RNA binding specificities, recognizing RNA
      stem-loop structures which differ primarily in the nucleotide sequences of their
      loops. We sought to convert MS2 coat protein to the RNA binding specificity of GA
      through the introduction of GA-like amino acid substitutions into the MS2 coat
      protein RNA-binding site. The effects of the mutations were determined by
      measuring the affinity of the coat protein variants for RNA in vitro and by
      measuring translational repression in vivo. We found five substitutions that
      affect RNA binding. One dramatically reduces binding of MS2 coat protein to both
      operators. Three others compensate for this defect by nonspecifically
      strengthening the interaction. Another substitution accounts for the ability to
      recognize the differences in the RNA loop sequence.

PMID- 8132639
TI  - Biosynthesis of N-glycolylneuraminic acid-containing glycoconjugates.
      Purification and characterization of the key enzyme of the cytidine monophospho-N
      acetylneuraminic acid hydroxylation system.
AB  - We have proposed that cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc)
      hydroxylation is carried out by a multienzyme system involving CMP-NeuAc
      hydroxylase (the terminal enzyme of the system), cytochrome b5, and an NADH
      dependent cytochrome b5-reducing factor (Kozutsumi, Y., Kawano, T., Yamakawa, T.,
      and Suzuki, A. (1990) J. Biochem. 108, 704-706). The CMP-NeuAc hydroxylase was
      purified to homogeneity from the cytosolic fraction of mouse liver, using ion
      exchange columns, a Red-Sepharose column, and a soluble cytochrome b5-immobilized
      Sepharose column. The purified enzyme exhibited a single band (64 kDa) on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and a single peak (58 kDa) on
      gel permeation chromatography, indicating that it is composed of a single
      polypeptide chain. The absorption spectrum did not indicate the presence of a
      heme prosthetic group in the enzyme. Atomic absorption spectrometry and an
      inhibition test using an iron chelator indicate that the enzyme contains non-heme
      iron as an electron acceptor. A reconstitution experiment with the purified CMP
      NeuAc hydroxylase, soluble cytochrome b5, and recombinant NADH-cytochrome b5
      reductase revealed that these three factors are essential for the reaction. The
      hydroxylase exhibited high affinity to CMP-NeuAc (Km = 5 microM) and was greatly
      stabilized by CMP-NeuAc. The molecular activity of the enzyme (approximately
      500/min) is much lower than that reported for NADH-cytochrome b5 reductase,
      suggesting that the activity or amount of hydroxylase is rate-limiting in CMP-N
      glycolylneuraminic acid (NeuGc) biosynthesis. These results, together with the
      previous observation that the level of CMP-NeuAc hydroxylase activity was
      associated with the expression of NeuGc in various tissues, support the notion
      that the enzyme is the key for regulation of the overall velocity of CMP-NeuAc
      hydroxylation and consequently for the expression of NeuGc-containing
      glycoconjugates.

PMID- 8132640
TI  - Histidyl phosphorylation and dephosphorylation of P36 in rat liver extract.
AB  - Protein histidine kinase (Motojima, K., and Goto, S. (1993) FEBS Lett. 319, 75
      79) and phosphatase in rat liver extract were characterized. The histidine kinase
      was recovered mostly in the membrane and the phosphatase in the soluble fraction.
      The kinase and its substrate 36-kDa protein (P36) were co-solubilized from the
      membrane under conditions in which most of the other kinases, and their substrate
      proteins were not solubilized. The solubilized kinase and P36 were co-eluted
      after high pressure liquid chromatography gel filtration, showing an apparent
      molecular mass of 70-75 kDa. They were also co-eluted after ion exchange
      chromatography. These characteristics, together with its complete resistance to
      genistein, indicate that the rat liver histidine kinase is not cognate to the
      yeast enzyme (Huang, J., Nasr, M., Kim, Y., and Matthews, H.R. (1992) J. Biol.
      Chem. 267, 15511-15515). The phosphatase that dephosphorylates histidyl
      phosphorylated P36 was also studied using rat liver subcellular fractions and in
      vitro phosphorylated P36 as the substrate. The characteristics of the
      phosphatase, that is, 1) Mg2+ requirement for activity, 2) apparent molecular
      mass of 45 kDa by high performance liquid chromatography gel filtration, and 3)
      resistance to 100 microM okadaic acid, suggest that the primary phosphatase
      active in vitro is protein phosphatase 2C.

PMID- 8132641
TI  - Positive and negative regulation of the erythropoietin gene.
AB  - In order to investigate positive and negative regulatory elements of the
      erythropoietin (Epo) gene, synthetic oligonucleotides were designed to control
      Epo transcription by means of an antigen strategy. We devised a new method for
      detecting regulatory elements of genes that have a weak promoter. Synthetic
      oligonucleotides were incubated with Hep3B cells in the presence or absence of
      CoCl2 or hypoxia. To exclude the effect of translational regulation, Epo mRNA
      concentration was determined by competitive polymerase chain reaction. The
      addition of antisense oligonucleotide for CACCC elements decreased the production
      of Epo mRNA in a dose-dependent fashion when cells were stimulated by CoCl2 or
      hypoxia. In contrast, the addition of antisense oligonucleotide for the GATA
      element caused a dose-dependent stimulation of Epo mRNA production either in the
      presence or absence of CoCl2 or hypoxia. Triple helix formation was revealed by
      electrophoresis. CACCC elements were demonstrated to be positive regulatory
      elements of the Epo gene, whereas the GATA element was a negative regulatory
      element. Furthermore, by gel mobility shift assays, we demonstrated evidence for
      the presence of factors in Hep3B cell nuclear extract that specifically bind to
      CACCC or GATA elements. Based on these observations, we presented the possibility
      that triple helix formation could serve as a novel means for transcriptional
      regulation of the gene.

PMID- 8132642
TI  - Deletion of the receptor MOM19 strongly impairs import of cleavable preproteins
      into Saccharomyces cerevisiae mitochondria.
AB  - The mitochondrial outer membrane proteins MOM19 and MOM72 are thought to function
      as import receptors for nuclear encoded preproteins. Different views exist about
      the importance of each receptor in the import of cleavable and noncleavable
      preproteins into mitochondria. Here we cloned and sequenced MOM19 from
      Saccharomyces cerevisiae and constructed a gene disruption mutant. Yeast cells
      lacking MOM19 were unable to grow on nonfermentable carbon sources and were slow
      in growing on a fermentable medium, while the growth of yeast cells lacking MOM72
      (Mas70p) was much less impaired. delta MOM19 cells accumulated considerable
      amounts of mitochondrial preproteins in vivo. The import of cleavable preproteins
      into isolated delta MOM19 mitochondria was strongly inhibited, while import of
      the noncleavable ADP/ATP carrier and phosphate carrier was only slightly
      inhibited. The reciprocal situation was found for protein import into delta MOM72
      mitochondria. In particular, import of the cleavable precursor of cytochrome c1
      into delta MOM72 mitochondria was, in agreement with a previous report (Hines,
      V., and Schatz, G. (1993) J. Biol. Chem. 268, 449-454), found to be partially
      inhibited, yet a much stronger inhibition of import was seen into delta MOM19
      mitochondria. The direct comparison of protein import into yeast mutants of
      either receptor yields a unifying hypothesis on mitochondrial preprotein
      targeting; both receptors have an overlapping specificity, and MOM19 plays a
      major role for cleavable preproteins. Interestingly, the primary sequence of
      MOM19 predicts the presence of a tetratricopeptide motif that was also found in
      MOM72, in the peroxisomal membrane protein PAS8/PAS10, and in several proteins
      involved in RNA synthesis or mitosis.

PMID- 8132643
TI  - Molecular basis for "null" lipoprotein(a) phenotypes and the influence of
      apolipoprotein(a) size on plasma lipoprotein(a) level in the baboon.
AB  - High plasma levels of lipoprotein(a) (Lp(a)) and its unique apolipoprotein,
      apo(a), are an independent risk factor for cardiovascular disease. Plasma Lp(a)
      levels vary over a 1000-fold range and are determined by the apo(a) locus, which
      has at least 34 alleles expressing apo(a) isoforms with molecular weights from <
      300,000 to > 800,000. In addition, "null" apo(a) alleles produce no detectable
      plasma apo(a). We used primary cultures of baboon hepatocytes to investigate the
      molecular basis for null apo(a) phenotypes. Immunoprecipitation of apo(a) after
      radiolabeling of hepatocytes revealed that some null alleles gave rise to
      intracellular protein products that were not secreted. Pulse-chase analysis and
      endoglycosidase digests demonstrated that these proteins were retained in the
      endoplasmic reticulum. We also examined the molecular basis for the documented
      inverse correlation between apo(a) size and plasma Lp(a) concentration. Steady
      state labeling and pulse-chase analysis of hepatocytes from animals expressing
      two isoforms of apo(a) revealed that the endoplasmic reticulum residence time of
      secreted apo(a) isoforms was determined by their size. This accounted for the
      inverse relationship between isoform size and level of secretion. We conclude
      that the efficiency of post-translational processing of apo(a) is a major
      determinant of plasma Lp(a) concentration.

PMID- 8132644
TI  - In vitro processing of recombinant G protein gamma subunits. Requirements for
      assembly of an active beta gamma complex.
AB  - The gamma subunits of the heterotrimeric G proteins (G gamma) are subject to
      carboxyl-terminal processing. This processing involves prenylation of a cysteine
      residue initially 4 amino acids from the carboxyl terminus, endoproteolytic
      truncation of the 3 terminal amino acids, and methylation of the now carboxyl
      terminal prenylcysteine residue. The significance of each of these modifications
      in the ultimate properties of G proteins is not yet clear. We have developed in
      vitro systems for the production of the three processing intermediates
      (unmodified, prenylated, and truncated-prenylated) for two G gamma subunits, one
      which is subject to farnesylation (G gamma 1) and one which is geranylgeranylated
      (G gamma 2). Assessment of the functional consequences of the processing of G
      gamma was found to require reconstitution of the polypeptides with a G protein
      beta subunit (G beta). The ability of recombinant G beta, produced in Sf9 cells,
      to assemble into stable beta gamma complexes (G beta gamma) with each of the G
      gamma processing intermediates was assessed. Both prenylated and unprenylated G
      gamma subunits formed stable complexes with G beta, but surprisingly, neither of
      the truncated-prenylated G gamma subunits were competent for this assembly. The G
      beta gamma complexes which were formed were examined for their ability to
      interact with a G protein alpha subunit (G alpha). Only those G beta gamma
      complexes containing a prenylated G gamma subunit were functional in this assay.
      These data indicate that: 1) prenylation of G gamma is not required for G beta
      gamma assembly; 2) assembly of the G beta gamma complex occurs prior to the
      proteolytic processing of G gamma; and 3) G beta gamma complexes require
      prenylated G gamma for interaction with G alpha.

PMID- 8132645
TI  - Inherent versatility of P-450 oxygenase. Conferring dehydroepiandrosterone
      hydroxylase activity to P-450 2a-4 by a single amino acid mutation at position
      117.
AB  - Mouse steroid 15 alpha-hydroxylase P-450 2a-4 is restricted in its substrate
      specificity to the delta 4, 3-ketone steroids such as androstenedione. As a
      result, the P-450 exhibits little hydroxylase activity toward delta 5, 3
      hydroxysteroids including dehydroepiandrosterone (DHEA). A single amino acid
      mutation of Ala at position 117 to Val, however, is enough to confer a high DHEA
      hydroxylase activity to P-450 2a-4 with 7 alpha-OH DHEA as one of the two major
      hydroxylated metabolites. Mouse coumarin 7-hydroxylase P-450 2a-5 contains Val at
      position 117, but it exhibits very low DHEA hydroxylase activity. P-450 2a-5
      acquires high DHEA hydroxylase activity, however, by a mutation of Phe-209 to
      Asn. Moreover, the mutant P-450 2a-5 loses its activity when Val is replaced by
      Ala at position 117. The residue at position 117, therefore, plays the principal
      role in the determination of the DHEA hydroxylase activity of the P-450s.
      Conversely, mutations at residue 117 have little effect on the androstenedione
      hydroxylase activities of the P-450s. Further modeling of the DHEA binding
      orientation in the substrate-heme pocket of bacterial P-450cam (Iwasaki, M.,
      Darden, T., Pedersen, L., Davis, D. G., Juvonen, R. O., Sueyoshi, T., and
      Negishi, M. (1993) J. Biol. Chem. 268, 759-762) provides support for the
      hypothesis that the type of residue at position 117 determines the steroid
      substrate specificity of the P-450 depending on the substituent at the C3
      position of steroid molecule.

PMID- 8132646
TI  - Identification of bacteriophage phi 29 prohead RNA domains necessary for in vitro
      DNA-gp3 packaging.
AB  - Functional domains of the bacteriophage phi 29 prohead RNA (pRNA) that are
      essential for in vitro packaging of DNA-gp3 into the prohead were mapped using
      pRNA mutants. Oligonucleotide-directed mutant pRNAs were produced that contained
      deletions and sequence alterations but were predicted to retain the overall
      secondary structure of wild-type pRNA. Mutant pRNAs were compared to wild-type
      pRNA for prohead binding in a competition assay and for DNA packaging in the
      defined in vitro system. The prohead binding site was previously localized to
      residues 22-84 on the 120-residue domain I of pRNA by ribonuclease footprinting
      (Reid, R. J. D., Bodley, J. W., and Anderson, D. (1994) J. Biol. Chem. 269, 5157
      5162). Mutations of pRNA within the prohead binding site resulted in substantial
      loss of prohead binding capacity, while mutations outside of the footprint had
      moderate effects on prohead binding. DNA-gp3 packaging activity was correlated
      with pRNA binding activity for mutations within the footprint. This mutational
      analysis showed that both sequence and secondary structure of residues 40-91 of
      pRNA were crucial for prohead binding and that elements of the A helix formed
      from residues 1-28 and 117-92 were needed for DNA packaging functions other than
      prohead binding.

PMID- 8132647
TI  - GP-3, a newly characterized glycoprotein on the inner surface of the zymogen
      granule membrane, undergoes regulated secretion.
AB  - We have recently reported the cloning of the rat zymogen granule membrane
      glycoprotein GP-3 and the related pancreatic secretory lipase (Wishart, M. J.,
      Andrews, P. C., Nichols, R., Blevins, G. T., Logsdon, C.D., and Williams, J. A.
      (1993) J. Biol. Chem. 268, 10303-10311). Specific antipeptide antibodies were
      generated against both GP-3 and secretory lipase and used for the biochemical and
      physiological characterization of GP-3. Western blotting confirmed that GP-3 was
      found exclusively in zymogen granule membranes and was absent from zymogen
      granule content which contains the majority of secretory lipase. Extraction of
      zymogen granule membranes with Triton X-114 showed GP-3 to be significantly more
      hydrophobic than lipase. The GP-3 amino acid sequence contains one potential N
      linked glycosylation site at Asn-336. The loss of concanavalin A labeling after
      both chemical deglycosylation with trifluoromethanesulfonic acid and enzymatic
      deglycosylation with N-glycanase showed GP-3 to possess a small N-linked
      oligosaccharide side chain. Digestion of intact and permeabilized zymogen
      granules with the nonspecific protease Pronase localized GP-3 to the inner
      surface of zymogen granule membranes. Since GP-3 is resident on the inner surface
      of the zymogen granule membrane, it should appear on the outer cellular surface
      after exocytosis. Although membrane attachment of GP-3 was resistant to treatment
      with phosphatidylinositol-specific phospholipase C, we observed that GP-3 is
      released into the pancreatic juice and that secretion of GP-3 was greatly
      enhanced by cholecystokinin.

PMID- 8132648
TI  - Isolation, cDNA sequences, and biochemical characterization of the major
      cyclosporin-binding proteins of Toxoplasma gondii.
AB  - The activities of the immunosuppressive, antifungal compounds cyclosporin A
      (CsA), FK-506, and rapamycin are dependent upon high affinity binding proteins
      collectively termed immunophilins. We report the isolation, biochemical
      characterization, and amino acid sequences of two major CsA-binding proteins,
      cyclophilins, from the pathogenic protozoan, Toxoplasma gondii. The 18.5- and 20
      kDa molecular mass proteins exhibit peptidylproline cis-trans-isomerase activity,
      which is inhibitable by 10(-8) M CsA. The amino acid sequences of these two
      proteins, deduced from cDNA clones, reveal up to 70% amino acid identity to
      previously isolated cyclophilins. The 18.5-kDa protein appears to be synthesized
      as a precursor with a 15 amino acid signal peptide. The amino-terminal region of
      the mature 20-kDa protein has significant homology to the B subunit of the
      calmodulin-dependent phosphatase, calcineurin. The two T. gondii cyclophilins are
      products of different genes and appear to have different subcellular
      distributions.

PMID- 8132649
TI  - RESP18, a novel endocrine secretory protein transcript, and four other
      transcripts are regulated in parallel with pro-opiomelanocortin in melanotropes.
AB  - The homogeneous nature of the rat intermediate pituitary makes it a powerful
      model system in which to study peptide hormone secretion. Adult male rats were
      treated with bromocriptine, a dopamine agonist, or haloperidol, a dopamine
      antagonist, for 3 weeks. In cDNA libraries prepared from the neurointermediate
      pituitaries of these rats, pro-opiomelanocortin (POMC) expression exhibited the
      expected decrease in response to bromocriptine, and increase in response to
      haloperidol. We report the identification of six transcripts that are coregulated
      with POMC in the intermediate pituitary by these dopaminergic agents. In addition
      to demonstrating parallel dopamine-regulated expression of carboxy-peptidase E,
      chromogranin B, binding protein/glucose-regulated protein, and tenascin, two
      novel regulated transcripts are described. The expression of one of these novel
      transcripts, RESP18, is limited to neural and endocrine tissue. The RESP18
      transcript is approximately 800 nucleotides in length; its cognate translation
      product is 20 +/- 1 kDa, contains a putative signal sequence, and has many
      characteristics of a secreted protein. Cell-free translation experiments in the
      presence of microsomal membranes demonstrate that the 20 +/- 1-kDa RESP18 protein
      is cleaved to an 18 +/- 1-kDa protein and sequestered within the lumen of the
      rough endoplasmic reticulum. Tissue in situ hybridization analysis shows that
      RESP18 mRNA is highly expressed in both the intermediate and anterior pituitary,
      as well as in the paraventricular and supraoptic nuclei of the hypothalamus.

PMID- 8132650
TI  - A developmentally regulated cell surface receptor for a density-sensing factor in
      Dictyostelium.
AB  - Conditioned medium factor (CMF) is an 80-kDa glycoprotein which is the signal in
      a cell density-sensing system used by developing Dictyostelium cells. CMF is
      slowly secreted by cells when they starve, and the extracellular level of CMF
      then becomes an indicator of the density of starving cells. To examine how CMF is
      sensed, we have made bacterially synthesized recombinant CMF and found that it
      has as much activity as native CMF, indicating that glycosylation is not part of
      the active site of CMF. Expression of recombinant fragments of CMF indicates that
      the active site lies within an 88-amino acid region near the N terminus. To
      determine whether CMF is sensed by cell surface receptors, we examined binding of
      iodinated recombinant CMF to live cells. We found saturable binding to 6-h
      starved cells at 3.9 x 10(4) molecules/cell with a KD of 2.1 nM. The binding
      saturates in 30 min, and a Scatchard plot indicates that there is only one class
      of receptor. The binding is competed off by the addition of either the native or
      recombinant CMF, or the 88-amino acid active fragment region; no binding
      competition is seen from the nonactive regions or other proteins. Very little
      binding to vegetative cells is seen, with maximal binding seen in cells starved
      for 6-8 h. The amount of cell surface CMF binding then decreases during later
      development. Normal levels of CMF binding are seen to CMF- cells, indicating that
      CMF is not required for the accumulation of its own receptor.

PMID- 8132651
TI  - Functional characterization of a unique liver gene promoter.
AB  - Human phenylalanine hydroxylase (PAH) is specifically expressed in the liver to
      convert L-phenylalanine to L-tyrosine. Deficiency of the PAH enzyme causes
      classic phenylketonuria, a common genetic disorder. The human PAH gene has a TATA
      less promoter with multiple transcriptional initiation sites. A 9-kilobase DNA
      fragment 5'-flanking to the human PAH gene is sufficient to confer tissue- and
      developmental stage-specific expression of a reporter gene in transgenic mice.
      Deletion studies showed that the -121-base pair proximal promoter still retained
      a significant level of activity in hepatic cells. At least two protein binding
      sites, PAH-A and PAH-B, were identified in the proximal region of the human PAH
      promoter using rat liver nuclear extract. The PAH-A site covers a unique
      palindromic sequence, and the PAH-B site contains CCCTCCC repeats. Both elements
      are ubiquitous and essential regulatory elements for transcriptional activity.
      Nuclear protein factors that bind to the PAH-A and -B sites are detected in
      different cell types and are distinct from previously characterized transcription
      factors. No tissue-specific transcription factor binding sites have been detected
      within the proximal promoter region of the human PAH gene. These results suggest
      that the PAH gene promoter has a unique organization of regulatory elements for
      its tissue-specific expression in comparison with other liver gene promoters.

PMID- 8132652
TI  - A highly active ubiquinol-cytochrome c reductase (bc1 complex) from the colorless
      alga Polytomella spp., a close relative of Chlamydomonas. Characterization of the
      heme binding site of cytochrome c1.
AB  - The alga Polytomella spp. offers extraordinary advantages in the preparation of
      mitochondria since it lacks chloroplasts and a cell wall. In this work the
      mitochondrial bc1 complex from Polytomella spp. was solubilized and purified by
      ion exchange chromatography. The complex was found to be composed of 10
      polypeptides and exhibited high rates of ubiquinol-cytochrome c oxidoreductase
      activity (> 300 s-1) sensitive to antimycin and myxothiazol. The molecular mass
      of the bc1 complex from Polytomella spp. was assayed by gel filtration and
      estimated to be of 256,300 Da. Therefore, this complex exhibits the unique
      property of behaving as a monomer. Amino-terminal sequencing of cytochrome c1
      identified 7 residues, from which a deoxyoligonucleotide was designed. A second
      deoxyoligonucleotide was constructed based on a highly conserved region of the c1
      type cytochromes. With these probes, a fragment of the cytochrome c1 gene was
      amplified by polymerase chain reaction and sequenced. The deduced sequence of the
      apoprotein exhibited a consensus binding site CXXCH. The data suggest that the
      cytochrome c1 from Polytomella spp. differs from other protoctists like Crithidia
      and Euglena, i.e. it exhibits a heme binding domain structurally related to the
      bovine, yeast, and Neurospora c1 type cytochromes.

PMID- 8132653
TI  - Cloning and molecular characterization of three genes, including two genes
      encoding serine hydroxymethyltransferases, whose inactivation is required to
      render yeast auxotrophic for glycine.
AB  - The genes encoding both the cytosolic and mitochondrial serine
      hydroxymethyltransferases (SHM2 and SHM1, respectively) and a third unidentified
      gene of the yeast Saccharomyces cerevisiae have been isolated and their
      nucleotide sequences determined. Analysis of the predicted amino acid sequence of
      the amino-terminal regions, sequence comparison with other genes encoding SHMT
      enzymes, and subcellular fractionation studies all suggested that the SHM1 gene
      encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme.
      The SHM2 gene but not the SHM1 gene has putative GCN4 sites upstream of the
      putative TATA box, suggesting regulation of its transcription by the general
      amino acid control system. Yeast mutants with disruptions at each SHM gene and in
      both genes were constructed and all mutants had the same growth requirements as
      the parental strains. Mutagenesis of the double-disrupted, shm1 shm2 yeast
      yielded strains of a single complementation group that are auxotrophic for
      glycine. Complementation of the glycine auxotrophy using a yeast genomic library
      retrieved the SHM1 and SHM2 genes and a third gene designated GLY1. Gene
      disruption studies demonstrated that inactivation of SHM1, SHM2, and GLY1 is
      required to yield yeast that are completely auxotrophic for glycine.

PMID- 8132654
TI  - Regulated intracellular degradation of apolipoprotein B in semipermeable HepG2
      cells.
AB  - A digitonin-permeabilized HepG2 cell system has been developed and used to
      characterize the pathway responsible for apolipoprotein B100 (apoB) degradation.
      Degradation of 35S-labeled apoB occurred after an initial lag period and resulted
      in the loss of approximately 75.8% of apoB after 2 h of chase. The degradation
      rate in permeabilized cells was slower than that in intact cells, but
      approximately the same percentage of apoB was lost over 2 h of chase. The loss of
      intact apoB in permeabilized cells coincided with the appearance of a number of
      degradation fragments, including 335- and 70-kDa fragments. The detection of a 70
      kDa fragment was a sensitive indicator of degradation. ApoB degradation was
      inhibited at temperatures below 37 degrees C and maximally activated at 42
      degrees C. Degradation was also pH-dependent, with inhibition at pH > or = 7.5.
      ApoB decay was stimulated by ATP supplementation but not GTP and was inhibited in
      the presence of energy inhibitors. Degradation was not significantly affected by
      cycloheximide. However, the stability of the 70-kDa fragment was prolonged with
      cycloheximide. Preincubation of cells with brefeldin A and nocodazole, as well as
      monensin, did not diminish the degradation of intact apoB or the appearance of
      the 70-kDa fragment, suggesting a lack of requirement for intracellular transport
      from the endoplasmic reticulum. Among the various protease inhibitors tested,
      degradation was most sensitive to N-acetylleucylleucylnorleucinal (ALLN), which
      abolished the generation of the 70-kDa fragment in a dose-dependent manner. ALLN
      sensitive degradation of apoB was unaffected by the calcium ionophore, A23187.
      Interestingly, degradation of unglycosylated apoB, detected in tunicamycin
      pretreated cells, occurred earlier, resulted in generation of additional
      fragments, and was largely uninhibited by ALLN. In summary, apoB degradation
      occurs in permeabilized HepG2 cells by a temperature- and pH-sensitive, pre-Golgi
      degradation system and is catalyzed by a calcium-independent, ALLN-sensitive
      protease. Specificity of the initial apoB cleavage may require the proper N
      linked glycosylation of the protein in the endoplasmic reticulum.

PMID- 8132655
TI  - Transmembrane topology and sites of N-glycosylation of inositol 1,4,5
      trisphosphate receptor.
AB  - To define the transmembrane topology of the inositol 1,4,5-trisphosphate receptor
      (InsP3R), we determined the subcellular location of the hydrophilic segment
      (residues 2463-2529 of mouse type 1 InsP3R) believed to be located at the luminal
      side of the endoplasmic reticulum (ER) in the six-transmembrane model but at the
      cytoplasmic side in the eight-transmembrane model. This hydrophilic segment
      includes two consensus sites for N-glycosylation (Asn-2475 and Asn-2503). We
      prepared an anti-peptide antibody against residues 2504-2523. Electron microscope
      immunocytochemical studies of mouse cerebellar Purkinje cells showed that binding
      of this antibody frequently occurs in the intracisternal space of the ER. We
      constructed three mutant receptors by site-directed mutagenesis of Asn to Gln
      (N2475Q, N2503Q, and N2475Q/N2503Q). By concanavalin A column chromatography of
      these receptors, we found that both Asn-2475 and Asn-2503 are glycosylated. These
      results indicate that residues 2504-2523, Asn-2475, and Asn-2503 are exposed to
      the ER lumen. We therefore propose that InsP3R has six membrane-spanning
      segments. Based on the transmembrane topology and subunit organization, we
      suggest that InsP3R is a member of the superfamily that includes the voltage- and
      second messenger-gated ion channels on the plasma membrane.

PMID- 8132656
TI  - Role of histidine 373 in the catalytic activity of coagulation factor XIII.
AB  - Factor XIII catalysis proceeds via formation of thioester acyl enzyme
      intermediate involving an active site cysteine residue at position 314. The
      contribution of other residues to catalysis has not been established. Earlier
      studies of the pH dependence of factor XIII activity suggested the existence of a
      putative active site histidine. We used chemical modification and oligonucleotide
      directed site-specific mutagenesis to investigate the role of histidines. Photo
      oxidation with methylene blue resulted in a complete loss of catalytic activity
      under conditions that oxidized histidine but did not affect the essential
      cysteine. Single substitution of each of the 14 histidine residues in the a
      subunit of factor XIII by asparagine or alanine led to mutants with catalytic
      activities generally not significantly different from the wild-type recombinant
      enzyme. The only exceptions were the H373N and H373A mutants that were poorly
      expressed, had no detectable rate of [14C]putrescine incorporation into
      dimethylcasein, and failed to cross-link fibrin gamma-chains. Thus, the a-subunit
      His-373 may function in the active site of factor XIII, by analogy with papain's
      mechanism, as a histidinium cation that increases the nucleophilicity of the
      essential Cys-314. Decreased expression levels of His-373 mutants also indicate
      that this residue may be critical for enzyme stability.

PMID- 8132657
TI  - Identification of regulatory elements in the cutinase promoter from Fusarium
      solani f. sp. pisi (Nectria haematococca).
AB  - The cutinase gene from Fusarium solani f. sp. pisi (Nectria haematococca) is
      induced upon contact with the plant cuticular polymer, cutin, by the unique
      hydroxy fatty acid monomers released by cutinase carried by virulent strains of
      the fungus, and this gene is also catabolite-repressed by glucose. Functional
      elements of the cutinase promoter were studied in vivo by transforming F. solani
      pisi with fusions of 5'-flanking regions of the cutinase gene and the gene
      encoding chloramphenicol acetyltransferase (cat). DNA-binding proteins from F.
      solani pisi were analyzed in vitro by gel shift experiments, methylation
      interference analysis, and UV-cross-linking experiments. Thus, we identified four
      promotor elements involved in cutinase gene regulation: a silencer, positive
      acting G-rich element, an element that binds a basal transcription factor, and a
      palindrome necessary for induction by cutin monomer. A silencer between -287 and 
      249 keeps basal gene expression low but also influences the inducibility of the
      gene. To restore high levels of induction, a G-rich positive-acting element with
      sequence similarities to other fungal elements acts as an antagonist to the
      silencer. Basal transcription is mediated by the first 141 base pairs of the
      cutinase promoter. The binding site of transcription factor CTF2 was identified
      between the TATA box and the transcription initiation sites. Gene induction by
      cutin monomers is regulated by CTF1, most probably a dimeric DNA-binding protein
      of 49 kDa with a palindromic recognition site at -170.

PMID- 8132658
TI  - The Saccharomyces cerevisiae MSI4 gene encodes the yeast counterpart of component
      A of Rab geranylgeranyltransferase.
AB  - We describe the isolation of MSI4 as a multicopy suppressor of ira1 (inhibitory
      regulator of Ras). We find it encodes a 66-kDa protein with three regions similar
      to component A of Rab geranylgeranyltransferase and Rab guanine nucleotide
      dissociation inhibitor. A gene disruption experiment showed that MSI4 is
      essential for cell growth. To investigate its functions further, we constructed a
      strain whose MSI4 is driven by the GAL1 promoter. This strain accumulated the
      endoplasmic reticulum precursor form of a vacuolar enzyme, carboxypeptidase Y,
      under the restrictive conditions. Moreover, we showed that the activity of
      geranylgeranyl-transferase for Ypt1p was very low in the mutant shifted to
      glucose medium. We propose that the MSI4 gene product is a yeast counterpart of
      component A of Rab geranylgeranyltransferase that is essential for Ypt1p to
      localize on membranes.

PMID- 8132659
TI  - Kinase activity of the type V transforming growth factor beta receptor.
AB  - The type V TGF-beta receptor purified from bovine liver plasma membranes
      catalyzed the phosphorylation of casein using [gamma-32P]ATP as co-substrate
      (Km,app approximately 10 microM). TGF-beta stimulated the casein phosphorylation
      by the type V receptor with a half-optimal concentration of approximately 0.3 nM.
      Both TGF-beta-stimulated and -unstimulated phosphorylations occurred at serine
      residues. Amino acid sequences of 32P-labeled peptides from reverse phase HPLC of
      the tryptic digests of casein 32P-phosphorylated by the type V receptor were
      analyzed by automated Edman degradation. Alignment of phosphorylation site amino
      acid sequences of the 32P-labeled peptides revealed a recognition motif (S-X
      E/S(P)) for the kinase activity of the type V receptor. The type V receptor
      catalyzed the phosphorylation of an octadecapeptide designated peptide SESTE
      (SKDIGS*ESITEDQAMEDKK) (the asterisk indicates the phosphorylated residue)
      containing the major phosphorylation site sequence of casein. The Km,app and Vmax
      for peptide SESTE were determined to be 0.3 microM and 2.2 nmol of 32P
      incorporation/min/mg of enzyme, respectively. The phosphorylation of peptide
      SESTE by the type V receptor was stimulated by TGF-beta or polylysine but
      inhibited by heparin. Like intact casein, peptide SESTE was phosphorylated at 2
      close serine residues (-S*-E-S*-T-E-) by the type V receptor. The type V receptor
      also phosphorylated a variant of peptide SESTE, peptide AESTE
      (SKDIGAES*TEDQAMEDKK). However, the type V receptor appeared not to phosphorylate
      peptide SEATE (SKDIGSEATEDQAMEDKKK) in which an alanine residue replaced 1 of the
      2 close serine residues (at the C-terminal side) of peptide SESTE. These results
      suggest that the type V receptor is capable of exerting interdependent
      phosphorylation.

PMID- 8132660
TI  - Ca(2+)-independent cytosolic phospholipase A2 from macrophage-like P388D1 cells.
      Isolation and characterization.
AB  - A novel form of an ATP-regulated, oligomeric, Ca(2+)-independent phospholipase A2
      (iPLA2) has been purified from the cytosol of the murine macrophage-like cell
      line P388D1. The purification procedure included ammonium sulfate precipitation
      and sequential column chromatography on octyl-Sepharose, ATP-agarose, Mono Q fast
      protein liquid chromatography (FPLC), and hydroxyapatite FPLC. The resulting
      enzyme preparation was purified over 400,000-fold with a final specific activity
      of approximately 5 mumol/min/mg using a mixed micelle assay system of Triton X
      100 and dipalmitoyl phosphatidylcholine (PC). The purified enzyme was Ca(2+)
      independent and did not show a preference for either sn-2 arachidonic acid or sn
      1 alkyl-ether containing phospholipids when utilizing mixed micelles as
      substrate. It was found to hydrolyze dipalmitoyl-PC approximately 4-fold faster
      than 1-palmitoyl-2-arachidonyl-PC and approximately 15-fold faster than 1-O
      hexadecyl-2-arachidonyl-PC. Triton X-100 increased the P388D1 iPLA2 activity with
      optimal activity found at a Triton/phospholipid molar ratio of 4:1. The purified
      enzyme was activated 2-6-fold by ATP as well as other di- and triphosphate
      nucleosides. This activation was sensitive to the concentration of Triton X-100
      present in the assay. SDS-polyacrylamide gel electrophoresis carried out on the
      purified enzyme yielded a single major band at a molecular weight of about
      80,000. However, radiation inactivation experiments, carried out on the cell
      homogenate, demonstrated a target size of 337 +/- 25 kDa, indicating that the
      catalytically active iPLA2 exists as a large oligomeric complex, either through
      self-aggregation or association of the enzyme with other proteins.

PMID- 8132661
TI  - Structure and expression of a novel, neuronal protein kinase C (PKC1B) from
      Caenorhabditis elegans. PKC1B is expressed selectively in neurons that receive,
      transmit, and process environmental signals.
AB  - The nematode Caenorhabditis elegans provides an advantageous system for
      investigating the regulation, expression, and functions of protein kinase C (PKC)
      isoforms. We cloned and characterized cDNAs encoding a novel C. elegans PKC
      designated PKC1B. The predicted PKC1B polypeptide contains features
      characteristic of the nPKC subfamily of PKC isoforms. The levels of PKC1B and its
      cognate mRNA vary over a 7-fold range during C. elegans postembryonic
      development. PKC1B protein and mRNA are abundant at the earliest larval stage,
      but their relative concentrations decrease coordinately in late larvae. Embryos,
      which are enriched in PKC1B mRNA, contain little PKC1B protein. Thus, PKC1B
      expression is regulated at a translational or post-translational level during
      early development. Cells engaged in PKC1B gene transcription were identified in
      transgenic C. elegans that carry the lacZ gene under the regulation of the PKC1B
      promoter. Staining for beta-galactosidase revealed PKC1B promoter activity
      exclusively in sensory neurons and interneurons. Immunofluorescence microscopy
      disclosed that the PKC1B polypeptide is located in the processes (axons and
      dendrites) and perinuclear regions of approximately 75 neurons that constitute
      the sensory circuitry of the nematode. The intracellular localization of PKC1B
      and the enzyme's differential solubility in ionic and nonionic detergents suggest
      that the kinase is associated with membranes and the cytoskeleton.

PMID- 8132662
TI  - The short-term activation of a rolipram-sensitive, cAMP-specific
      phosphodiesterase by thyroid-stimulating hormone in thyroid FRTL-5 cells is
      mediated by a cAMP-dependent phosphorylation.
AB  - To elucidate the mechanism causing the transient accumulation of intracellular
      cAMP in the FRTL-5 thyroid cell line, the short-term effect of thyroid
      stimulating hormone (TSH) on phosphodiesterase (PDE) activity was studied.
      Together with an increase in cAMP levels, TSH produced a significant increase in
      total PDE activity as early as 3 min, with a maximal stimulation reached after 15
      min. This short-term increase in PDE activity was dependent on the TSH
      concentration (ED50 = 4 x 10(-11) M TSH). Forskolin and dibutyryl cAMP produced
      an even larger stimulation than that produced by TSH, suggesting that the effect
      of TSH is mediated by cAMP. To determine the properties of the PDE forms
      activated by TSH, antibodies specific for the cAMP-PDEs were used to
      immunoprecipitate the PDEs present in control cells, and cells incubated for 15
      min in the presence of 10 nM TSH. Comparison of the activity recovered in the
      immunoprecipitation pellets demonstrated that TSH produced more than a 2.5-fold
      increase in the cAMP-PDE form(s) recognized by this antibody. Conversely, the
      activity remaining in the supernatants was not affected by the TSH treatment.
      Most of the activity recovered in the immunoprecipitation pellets (90%) was
      inhibited by 10 microM Rolipram, an inhibitor specific for the high affinity cAMP
      PDEs. No TSH stimulation of the Rolipram-insensitive PDE activity could be
      observed under these conditions. Western blot analyses with two different cAMP
      PDE specific antibodies showed that a 15-min stimulation with TSH induced the
      appearance of a new band with electrophoretic mobility slower than the
      polypeptide present in unstimulated cells. The appearance of this band did not
      require ongoing protein synthesis because it occurred in the presence of
      cycloheximide. Metabolic [32P]orthophosphate labeling of intact FRTL-5 cells
      indicated that the TSH treatment caused an increased 32P incorporation into a
      polypeptide that co-purified with the stimulated PDE activity and had an
      electrophoretic mobility identical to that of the cAMP-PDE. Okadaic acid, a
      potent inhibitor of protein phosphatase 1 and protein phosphatase 2A, elicited a
      potentiation of the TSH-stimulated PDE activity. The stimulating of a PDE with
      the same immunological properties and Rolipram sensitivity as the cAMP-PDE
      stimulated by TSH in the intact cells was reproduced, in a cell-free system, by
      incubating soluble extracts from FRTL-5 cells with the catalytic subunit of cAMP
      dependent protein kinase. These data provide evidence that TSH produces a rapid
      activation of a cAMP-PDE in the FRTL-5 cells through a cAMP-dependent
      phosphorylation.

PMID- 8132663
TI  - Purification and properties of a protein that binds to the C-terminal coding
      region of human c-myc mRNA.
AB  - The short half-life of c-myc mRNA is influenced by sequences in the 3'
      untranslated region and the C-terminal part of the coding region. In cell-free
      extracts, a polysomal protein binds to RNA corresponding to the coding region
      stability determinant. This and other observations suggest that the protein is
      bound to polysome-associated c-myc mRNA and protects the mRNA from a ribosome
      associated endoribonuclease (Bernstein, P.L., Herrick, D.J., Prokipcak, R.D., and
      Ross, J. (1992) Genes & Dev. 6, 642-654). Here, we describe a four-step
      purification of the binding protein: solubilization from ribosomes, ammonium
      sulfate precipitation, RNA affinity chromatography, and reverse-phase high
      performance liquid chromatography. The 70-kDa protein can be renatured from
      solutions containing sodium dodecyl sulfate or organic solvents, greatly
      facilitating its purification. Protein binding to c-myc coding region RNA is
      blocked by diamide and N-ethylmaleimide, indicating a requirement for sulfhydryl
      groups. The protein also binds to N-myc coding region RNA but with approximately
      5-fold lower affinity than to the comparable c-myc region. Excess c-myc
      competitor RNA induces 8-fold destabilization of c-myc mRNA in cell-free mRNA
      decay extracts. In contrast, N-myc coding region competitor RNA has no effect on
      c-myc mRNA half-life. Therefore, the protein we have purified probably affects c
      myc mRNA metabolism with high specificity.

PMID- 8132664
TI  - Hevein, a lectin-like protein from Hevea brasiliensis (rubber tree) is involved
      in the coagulation of latex.
AB  - Hevein, a lectin-like protein is the major protein of vacuolar structures called
      lutoids in the latex of rubber trees. We have shown both by in planta and ex
      planta studies that hevein is involved in the coagulation of latex by bringing
      together rubber particles. This polyvalent bridging between hevein and rubber
      particles is mediated by N-acetyl-D-glucosamine and involves a receptor
      glycoprotein of 22 kDa, which is localized on the surface of the rubber
      particles. The proposed role of hevein helps us to understand the mechanism of
      coagulation of latex and assigns a physiological intracellular function to one of
      the smallest lectins.

PMID- 8132665
TI  - Rat liver mitochondrial processing peptidase. Both alpha- and beta-subunits are
      required for activity.
AB  - Most nuclearly encoded mitochondrial proteins are synthesized with an amino
      terminal leader peptide that is cleaved by the mitochondrial processing peptidase
      (MPP). Purified rat liver MPP, like the Neurospora and yeast enzymes, consists of
      two nonidentical subunits, alpha (55 kDa) and beta (50 kDa). To confirm the
      functional authenticity of the recently cloned and sequenced cDNAs for the alpha-
      and beta-MPP subunits from rat liver and to study each subunit's participation in
      MPP activity, we have subcloned and expressed separately in Escherichia coli the
      mature sequence of each subunit as a fusion protein with the maltose-binding
      protein. After induction, about 80% of each expressed fusion protein was
      insoluble in aggregates or inclusion bodies, and 20% remained soluble in the
      supernatant. The fusion proteins in the soluble fraction were purified by
      affinity chromatography and treated with factor Xa, and the MPP subunits were
      purified to homogeneity. When mixed together, these subunits showed no activity,
      suggesting that they might be misfolded. Therefore, a reconstitution protocol was
      developed which consisted of denaturation in urea, dithiothreitol, and 2
      mercaptoethanol, followed by renaturation by dilution and dialysis under reducing
      conditions. With this procedure, active MPP was recovered from the mixed
      subunits, and it could be demonstrated that both alpha- and beta-MPP subunits
      were necessary for activity. Reconstituted recombinant MPP resembled the native
      rat liver enzyme as judged by its molecular weight, its inhibition by EDTA, and
      its ability to process a variety of mitochondrial precursor proteins
      appropriately to either an intermediate or a mature form.

PMID- 8132666
TI  - Functional nuclear pores reconstituted with beta 1-4 galactose-modified O-linked
      N-acetylglucosamine glycoproteins.
AB  - Nuclear pore proteins bearing O-linked N-acetylglucosamine (GlcNAc) are involved
      in nuclear transport, although a role for their glycosylation is not established.
      Xenopus egg extracts capable of reforming functional nuclei in vitro yielded
      nuclei with impaired transport and reduced nuclear pore density when depleted of
      wheat germ agglutinin-binding proteins. Many of the nuclear pores remaining in
      wheat germ agglutinin-depleted nuclei showed a striking loss of internal
      structure. Nuclear transport and normal nuclear pore structure were restored by
      the addition of nuclear pore glycoproteins from rat liver or Xenopus eggs.
      Glycoproteins modified by the addition of galactose to O-linked GlcNAc were also
      competent for assembling normal nuclear pores and restoring nuclear transport.
      Aphidicolin-sensitive DNA synthesis was unaffected by the removal or modification
      of O-linked GlcNAc glycoproteins. These data argue against a requirement for a
      lectin-like recognition of O-linked GlcNAc glycoproteins in nuclear pore
      assembly, nuclear transport, or DNA synthesis.

PMID- 8132667
TI  - Expression of the dibasic proprotein processing enzyme furin is directed by
      multiple promoters.
AB  - The prototype mammalian proprotein processing enzyme furin is shown to be encoded
      by three distinct FUR mRNA isoforms which differ only in their 5'-untranslated
      regions. By primer extension analysis, the transcription start sites of the three
      mRNA isoforms were defined. The genomic regions located immediately upstream of
      the three alternative transcriptional start sites were shown to possess promoter
      activity in transfection experiments using the luciferase encoding gene as
      reporter. In a liver cell line, the P1 promoter appeared to be the strongest; in
      a lung cell line, the P1A promoter. Human FUR promoter P1 but not P1A or P1B was
      transactivated by transcription factor C/EBP beta. Other members of this family
      of bZIP transcription factors, C/EBP alpha and C/EBP delta, were not able to
      transactivate the P1 promoter. Promoter P1A and P1B have characteristics of
      promoters of housekeeping genes. They lack TATA or CAAT boxes upstream of the
      transcription start site but are very GC-rich and contain several SP1 sites.
      Promoter P1, on the other hand, has a TATA box in the proximal promoter region.
      In electromobility shift assays and DNase I footprinting analysis, transcription
      factor SP1 was found to bind to the proximal region of the P1 promoter.
      Altogether, our results indicate that expression of the human FUR gene is
      directed by alternative promoters, housekeeping (GC-rich) as well as regulated
      (TATA-containing) promoters, suggesting that their differential use may be a
      mechanism to modulate levels of the furin enzyme.

PMID- 8132668
TI  - Ethanol inhibits neural cell-cell adhesion.
AB  - Gestational exposure to ethanol causes defects in neuronal migration,
      fasciculation, and synaptogenesis, developmental events that depend on the
      patterned expression and function of cell adhesion molecules (CAMs). Recombinant
      human osteogenic protein-1 (hOP-1) increases cell-cell adhesion and promotes cell
      clustering in proliferating neuroblastoma x glioma hybrid NG108-15 cells by
      strongly inducing N-CAM and L1. Here we show that concentrations of ethanol
      achieved during social drinking inhibit hOP-1-induced cell clustering without
      affecting cell proliferation, the induction and cell surface expression of N-CAM
      and L1, or the alternative splicing and sialylation of N-CAM. This inhibition was
      reproduced by other alcohols in proportion to their chain length, but not by
      teratogenic anticonvulsants or phenylalanine. Ethanol inhibition of hOP-1
      morphogenesis was inversely proportional to the concentration of hOP-1 and,
      hence, to the levels of N-CAM and L1. Low concentrations of ethanol (IC50 5-10
      mM) inhibited cell-cell adhesion in hOP-1-treated cells, and this action too was
      reproduced more potently by propanol and butanol. Ethanol may perturb brain and
      skeletal development by inhibiting CAM-mediated cell-cell interactions.

PMID- 8132670
TI  - Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen
      associated with metastasis contains leucine-rich repeats.
AB  - The monoclonal antibody 5T4 defines a human oncotrophoblast antigen expressed by
      a variety of carcinomas but with a restricted pattern of expression in normal
      adult tissues. The 5T4 antigen has been isolated from term placenta as a 72-kDa
      glycoprotein consisting of a 42-kDa core protein with extensive N-linked
      glycosylation. A cDNA has been isolated from a human placental library using
      pools of oligonucleotides based on amino acid sequence obtained from purified 5T4
      molecules. The predicted open reading frame encodes a protein of 420 amino acids
      with a molecular mass of 46 kDa and 8 potential N-glycosylation sites. There are
      N- and C-terminal hydrophobic segments corresponding to putative signal and
      membrane anchorage sequences, respectively. Northern analysis has demonstrated a
      major 2.5-kilobase mRNA present in cell lines serologically reactive with the
      monoclonal antibody 5T4. Comparison of the 5T4 protein sequence with current
      sequence data bases has identified the presence of leucine-rich repeats, which
      are found in a variety of proteins from yeast, insects, and mammals. The 5T4
      antigen expression is strongly associated with metastasis in colorectal and
      gastric cancer, and, hence, the possible functions of the gene product and its
      relationship to tumor growth and progression are discussed.

PMID- 8132669
TI  - Apolipoprotein B48-membrane interactions. Absence of transmembrane localization
      in nonhepatic cells.
AB  - Apolipoprotein B (apoB) is essential for the hepatic assembly and secretion of
      triglyceride-rich very low density lipoproteins. Recent studies have revealed
      that in both hepatic and nonhepatic cells a large percentage of newly synthesized
      apoB polypeptides engage in transmembrane interactions with the endoplasmic
      reticulum (ER). These apoB-membrane interactions have been implicated in the
      processes of lipoprotein assembly and regulation. To identify domains of apoB
      that are responsible for its transmembrane localization, overlapping 300 amino
      acid segments of human apoB48 (amino-terminal 48% of apoB) and two control
      proteins, human complement component C3 and mouse CD4, were appended to the amino
      terminal 77 amino acids of a soluble secretory precursor protein and expressed in
      COS-1 cells. While the integral membrane protein CD4 conferred predictable
      transmembrane orientation on the hybrid protein, as evidenced by its partial
      protease accessibility in intact microsomes, all of the apoB-containing proteins
      and the soluble secretory control, C3, were fully protease-resistant, consistent
      with their complete translocation into the ER. To determine if conformational
      properties of apoB are responsible for its transmembrane interactions with the
      ER, proteins containing the entire amino-terminal approximately 50% of apoB
      (apoB50) were expressed in COS-1 cells. Irrespective of whether targeting and
      translocation initiation were directed by a heterologous signal peptide or the
      native apoB signal peptide, apoB50 appeared to undergo complete membrane
      translocation into a protease-inaccessible compartment. These results demonstrate
      that the amino-terminal 50% of apoB lacks autonomous signals or properties that
      can fully block ER membrane translocation or promote any other form of stable
      transmembrane assembly in nonhepatic cells.

PMID- 8132671
TI  - Purification and reconstitution of an intestinal Na(+)-dependent neutral L-alpha
      amino acid transporter.
AB  - Using an improved reconstitution method, we have purified an Na(+)-dependent
      neutral L-alpha-amino acid transporter from rabbit small intestine to apparent
      homogeneity. The preparation solubilized with octaethylene glycol dodecyl ether
      (C12E8) was purified by successive chromatographies on DEAE-Toyopearl and lentil
      lectin-Sepharose 4B columns. The transport activity was assayed by reconstitution
      of the protein into liposomes. The specific activity of the final preparation was
      1364-fold that of brush border membrane vesicles. On sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, the active fractions gave one band of 90 kDa.
      Kinetic analysis using proteoliposomes reconstituted with the purified fraction
      showed that alanine transport was mediated by high affinity system with Kt value
      of 0.19 mM and Jmax value of 2.8 nmol/mg protein/s. Analysis of the amino acid
      composition of the purified transporter revealed that the transporter is very
      hydrophobic protein. From its specific activities for transport of individual
      amino acids this transporter was concluded to possess broad specificity for
      neutral L-alpha-amino acids. Furthermore, inhibition study of other amino acids
      allowed us to identify this transport pathway as the intestinal system B.

PMID- 8132672
TI  - OXBOX and REBOX, overlapping promoter elements of the mitochondrial F0F1-ATP
      synthase beta subunit gene. OXBOX/REBOX in the ATPsyn beta promoter.
AB  - Three positive (PR1-3) and one negative (NR1) transcriptional control domain have
      been tentatively mapped in the promoter of the human F0F1-ATP synthase beta
      subunit gene (ATPsyn beta) in the context of expression in myogenic cells.
      Lipofection of promoter-chloramphenicol acetyltransferase fusion constructs into
      C2C12 myogenic cells revealed that two of the three positive domains (PR1 and
      PR2) function in both myoblasts and myotubes, whereas the third positive domain
      (PR3) and the sole negative domain (NR1) seem to function only in myotubes. PR1
      contains a cluster of four CCAAT cis-elements, PR2 is a small 44-base pair region
      containing an SP1-like motif, and PR3 is a region previously shown to be
      recognized by both OXBOX- and REBOX-binding factors. By site-directed polymerase
      chain reaction linker mutations, the activity of the OXBOX/REBOX cis-element in
      myoblasts is shown to be masked by flanking sequences in PR3. The negative
      domain, NR1, is located between 300 and 1,000 base pairs upstream from the
      OXBOX/REBOX elements in a region containing multiple Alu repeats. Mobility gel
      shift analysis of DNA-protein complexes using competitor DNAs verified the
      involvement of both OXBOX- and REBOX-binding factors in PR3. Similar experiments
      show SP1-specific binding at PR2. These data with observations of OXBOX and REBOX
      specific binding of an OXBOX/REBOX-like region within the conserved sequence
      block C of the human mitochondrial DNA D-loop sequence are consistent with the
      idea that OXBOX- and REBOX DNA-binding factors coordinate the expression of
      mitochondrial energy genes in highly oxidative tissues by working with well
      characterized general transcription factors such as SP1 and CCAAT DNA-binding
      proteins, which exist in the nucleus, and MTF, which exists in the mitochondrion.

PMID- 8132673
TI  - Analysis of the competition between nucleosome formation and transcription factor
      binding.
AB  - We have studied the competitive binding of histones and the Rous sarcoma virus
      internal enhancer binding factor (IBF) factor (which recent studies indicate is
      almost certainly cEBP beta). We find that histones and IBF are incapable of
      forming a ternary complex with a 159-base pair (bp) fragment of DNA containing a
      single IBF binding site and that histones and factor are mutually exclusive in
      binding. We have analyzed the various physical parameters of binding, in an
      attempt to understand how the factor might establish an exclusive binding in the
      cell. The stability of the nucleosome and the factor-DNA complex have been
      determined, and in addition a minimum value for the affinity of the histone
      octamer has been computed. We find that in simple competition the IBF can
      successfully compete, only if the substrate DNA is shorter than 140 bp. The
      relevance of these results is discussed in terms of a kinetic model for
      successful factor competition during the replication of the factor binding site
      in the cell.

PMID- 8132674
TI  - Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix
      associated protein with a distinctive pattern of expression in mouse cells and
      tissues.
AB  - We have isolated cDNA clones corresponding to a novel mouse metalloproteinase
      inhibitor. Five overlapping cDNA clones contain most of the information for a
      prominent 4.5-kilobase transcript that was detected in RNA from mouse fibroblasts
      and adult tissues. Sequence analysis revealed an open reading frame (ORF) for a
      protein of 212 amino acids that is 80% identical to chicken inhibitor of
      metalloproteinases-3 (ChIMP-3). The 3'-untranslated sequence also showed
      remarkable conservation with the chicken gene. The ORF directed the expression of
      a 24-kDa protein in COS-1 cells that localized to the extracellular matrix (ECM).
      On the basis of these similarities we propose to identify the new gene as murine
      tissue inhibitor of metalloproteinases-3 (TIMP-3). Mouse C3H 10T1/2 fibroblasts
      produced a 24-kDa metalloproteinase inhibitor that also localized to the ECM and
      was recognized by a polyclonal antibody to ChIMP-3. Like TIMP-1, TIMP-3 was
      highly inducible in mouse C3H 10T1/2 fibroblasts by phorbol ester (PMA),
      epidermal growth factor (EGF), and transforming growth factor-beta 1, but nuclear
      run-on assays showed that the on/off transcription kinetics were faster for TIMP
      3 than TIMP-1. A major difference in vitro was the stimulation of expression of
      TIMP-3 by dexamethasone which inhibits EGF- and PMA-induced TIMP-1 transcription.
      Also, TIMP-3 showed a distinctive pattern of expression in adult tissues with
      abundant transcripts detected in kidney, lung, and brain but only low levels
      detected in bone, a prominent location of TIMP-1 transcripts. We propose that
      TIMP-3 functions in a tissue-specific fashion as part of an acute response to
      remodeling stimuli.

PMID- 8132675
TI  - Protein kinase C-mediated phosphorylation and calmodulin binding of recombinant
      myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related
      protein.
AB  - The myristoylated alanine-rich C kinase substrate (MARCKS) and the MARCKS-related
      protein (MRP) are members of a distinct family of protein kinase C (PKC)
      substrates that also bind calmodulin in a manner regulated by phosphorylation by
      PKC. The kinetics of PKC-mediated phosphorylation and the calmodulin binding
      properties of intact, recombinant MARCKS and MRP were investigated and compared
      with previous studies of synthetic peptides spanning the PKC phosphorylation
      site/calmodulin binding domains (PSCBD) of these proteins. Both MARCKS and MRP
      were high affinity substrates for the catalytic fragment of PKC, and their
      phosphorylation occurred with positive cooperativity (MARCKS: S0.5 = 100 nM, KH =
      1.43; MRP: S0.5 = 238 nM, KH = 1.72). These affinities are similar to the values
      determined from studies of their respective PSCBD peptides. Two-dimensional
      mapping of MRP and its synthetic PSCBD peptide yielded identical patterns of
      tryptic phosphopeptides, indicating that, as in the case of MARCKS, all of the
      PKC phosphorylation sites in MRP lie within the 24-amino acid PSCBD. Sequence
      analysis of tryptic phosphopeptides revealed that the first and third, but not
      the second, serines in the MRP PSCBD were phosphorylated by PKC. Both MARCKS and
      MRP bound dansyl-calmodulin with high affinity, with a Kapp of 4.6 and 9.5 nM,
      respectively. Phosphorylation of MARCKS and MRP by PKC disrupted the protein
      calmodulin complexes, with half-lives of 4.0 and 3.5 min, respectively. These
      studies suggest that intact, recombinant MARCKS and MRP are accurately modeled by
      their synthetic PSCBD peptides with respect to PKC phosphorylation kinetics and
      their phosphorylation-dependent calmodulin binding properties.

PMID- 8132676
TI  - Mutations in the zinc-finger region of the yeast regulatory protein ADR1 affect
      both DNA binding and transcriptional activation.
AB  - The expression of the yeast ADH2 gene is controlled by the transcriptional
      activator ADR1, a zinc-finger protein that binds to an upstream activating
      sequence (UAS1) in the ADH2 promoter. We report here the isolation of seven
      mutations in the ADR1-5c allele, defining five different amino acid changes, that
      suppress the enhanced ADH2 expression caused by the ADR1-5c allele. Each of the
      mutations was shown to reduce the activation of ADH2 by a wild-type ADR1 gene,
      suggesting the mutations disrupt a domain important to the function of both the
      ADR1 and ADR1-5c proteins. All five amino acid changes occurred within the DNA
      binding domain of ADR1 and were shown to severely inhibit the ability of ADR1 to
      bind UAS1 in vitro. These mutations were found, however, to also affect the
      ability of ADR1 to activate transcription independent of its ability to bind DNA.
      These results indicate that the DNA-binding region of ADR1 is involved in both
      transactivation and DNA binding.

PMID- 8132677
TI  - Definition of the carbohydrate response element of the rat S14 gene. Context of
      the CACGTG motif determines the specificity of carbohydrate regulation.
AB  - Transcription of the S14 gene in primary hepatocytes is stimulated in response to
      increased carbohydrate metabolism. We have demonstrated previously that a 30-base
      pair (bp) segment of the S14 gene from -1457 to -1428 is a carbohydrate response
      element (ChoRE). This element contains a (5')CACGTG motif that is essential for
      control. DNase I footprinting experiments with liver nuclear extract revealed two
      factors binding within the S14 ChoRE. In transient transfection experiments,
      mutation of the upstream site between -1457 and -1450 did not affect the response
      to elevated glucose, whereas the downstream 21-bp site between -1448 and -1428
      was sufficient to mediate the glucose induction. Electrophoretic mobility shift
      assays indicated that the hepatic factor binding to this site in vitro is closely
      related or identical to the major late transcription factor (MLTF). However,
      replacement of the 21-bp S14 ChoRE with the authentic MLTF binding site from the
      adenovirus major late promoter failed to elicit the glucose response. By
      systematically exchanging bases between the functional S14 and nonresponsive
      adenovirus sites, the sequence (5')CACGTGNNNGCC was found to be essential for
      carbohydrate regulation. A segment containing this specific motif from the rat
      fatty acid synthase gene, another carbohydrate-responsive gene in hepatocytes,
      conferred a carbohydrate response when linked to the S14 promoter. Thus, the
      context of the CACGTG motif provides the specificity for regulation by
      carbohydrate metabolism.

PMID- 8132678
TI  - Complete cDNA encoding human phospholipid transfer protein from human endothelial
      cells.
AB  - Phospholipid transfer protein, with an apparent molecular mass of 81 kDa, was
      purified from human plasma. The NH2-terminal amino acid sequence of a 51-kDa
      proteolytic fragment obtained from phospholipid transfer protein allowed
      degenerate primers to be designed for polymerase chain reaction and the eventual
      isolation of a full-length cDNA from a human endothelial cDNA library. The cDNA
      is 1,750 base pairs in length and contains an open reading frame of 1,518
      nucleotides encoding a leader of 17 amino acids and a mature protein of 476
      residues. Northern blot analysis shows a single mRNA transcript of approximately
      1.8 kilobases with a wide tissue distribution. The gene was mapped to chromosome
      20 using a human/rodent somatic cell hybrid mapping panel. Phospholipid transfer
      protein was found to be homologous to human cholesteryl ester transfer protein,
      human lipopolysaccharide-binding protein, and human neutrophil bactericidal
      permeability increasing protein (20, 24, and 26% identity, respectively).

PMID- 8132679
TI  - Expression and regulation of basic fibroblast growth factor mRNA levels in mouse
      osteoblastic MC3T3-E1 cells.
AB  - Basic fibroblast growth factor (bFGF) is a potent mitogen for bone cells and is a
      constituent of the bone matrix. We have found that osteoblastic MC3T3-E1 cells
      expressed bFGF mRNA transcript of 4.5 kilobases (kb). We examined factors that
      regulate the expression of bFGF mRNA and protein in MC3T3-E1 cells. Treatment of
      MC3T3-E1 cells with bFGF (10 nM) for 4-48 h induced another 7-kb bFGF transcript
      at 4 h. Treatment of MC3T3-E1 cells with TGF beta (10 ng/ml) also induced the 7
      kb transcript of bFGF mRNA. In contrast, heparin, parathyroid hormone, and
      interleukin-1 had no effect on bFGF mRNA. Western blot analyses revealed that
      MC3T3-E1 cells produced a 24-kDa bFGF protein, which was increased by TGF beta.
      Immunofluorescence showed that bFGF protein was localized to the cytoplasm in
      serum-deprived MC3T3-E1 cells. Treatment of these cultures with medium containing
      fetal calf serum or TGF beta caused increased cytoplasmic staining for bFGF and
      marked shape change. Furthermore, in the cells treated with TGF beta there was
      both nuclear and cytoplasmic staining for the protein. These data demonstrate
      that bFGF mRNA and protein are expressed in osteoblastic cells and are regulated
      by treatment with TGF beta and bFGF. Production of bFGF may be important as an
      autocrine and paracrine mediator of bone cell replication, differentiation, and
      function.

PMID- 8132680
TI  - Evaluation of left ventricular function based on simulated systolic flow dynamics
      computed from regional wall motion.
AB  - Left ventricular (LV) chamber flow is undoubtedly influenced by the time
      dependent regional motion of the LV wall. In an attempt to obtain diagnostic
      parameters based on LV chamber flow, we computed the LV chamber, two-dimensional
      systolic velocity and pressure distribution for two right anterior oblique (RAO)
      ventriculograms: one normal, one with ischemic coronary artery disease, and
      several simulations with prescribed abnormal wall motion. The flow fields are
      obtained by solving the discretized two-dimensional Navier-Stokes equations for
      viscous, incompressible unsteady flow using the finite analytic method. These
      solutions were used as a basis for two LV assessment parameters: (1) local
      pressure gradient near the LV wall, and (2) the central ejection region (CER),
      defined as the region of flow domain in which the obtained velocity field vectors
      are aligned +/- 5 degrees from the LV long axis. A CER coefficient, R, derived
      from the location and orientation of the CER within the LV cavity, is defined
      such that R = 0 for a heart which produces no CER, and R = 1 for a heart whose
      contraction is perfectly even along the entire RAO LV outline. The computed local
      pressure gradients in the ischemic heart near the apical wall region were reduced
      compared with those computed in the normal heart. An observable decrease in
      magnitude of the pressure gradients in the apical region for increasing severity
      of abnormal wall motion was also indicated. However, the prescribed abnormal wall
      motion simulations generated reduced pressure gradients in regions of abnormal
      wall motion and normal regions as well. Therefore, the local wall pressure
      gradient may not be suitable for localization of coronary occlusion but for
      presence of disease only. The time-averaged CER coefficient was 0.709 for the
      normal heart and 0.453 for the diseased heart. The CER shifted toward the region
      of LV wall which exhibits the abnormal motion, and the CER coefficient decreased
      with increasing severity of abnormal wall motion. The CER coefficient provides a
      qualitative and quantitative measure of global function that regional wall motion
      analysis cannot provide, and is a parameter which is sensitive to regional and
      temporal abnormalities and the resulting compensatory actions which cannot be
      detected by global parameters.

PMID- 8132681
TI  - Ultrasonically determined elasticity and cortical density in canine femora after
      hip arthroplasty.
AB  - Effects of canine hip replacement (with a porous-coated femoral component) on the
      material properties of surrounding cortical bone were evaluated. The hypotheses
      were: (1) after four months of implantation, mechanical properties of the cortex
      would change, and (2) a collared implant would be associated with smaller changes
      than a collarless design. Unilateral total hip arthroplasty was performed in 15
      mixed-breed dogs. Nine received a collared and six received a collarless femoral
      component. Four months after implantation, longitudinal ultrasonic wave
      propagation velocities and bone mineral densities (from dual energy X-ray
      absorptiometry) were measured in harvested femora and used to calculate the axial
      elastic constitutive coefficients for the cortex surrounding the implants.
      Results showed no difference in bone elasticity or bone density between collared
      and collarless designs. Significant velocity decreases from control values (p <
      0.0001) were noted in all implanted femora at four months. Bone mineral densities
      also displayed decreased values after four months of implantation (p < 0.0145).
      Elastic coefficients were consistently less after four months of implantation
      when compared to control values (p < 0.0001). This alteration in material
      properties would affect load transfer into the implanted femur via the increased
      disparity between implant and bone stiffnesses regardless of the component
      design. Significant differences in the elastic coefficients between implanted and
      control femora support hypothesis 1. However, no group differences were found
      between collared and collarless implantations; thus, the study does not support
      hypothesis 2.

PMID- 8132682
TI  - Finite element modeling of damage accumulation in trabecular bone under cyclic
      loading.
AB  - A two-dimensional finite element model of an idealized trabecular bone specimen
      was developed to study trabecular bone damage accumulation during cyclic
      compressive loading. The specimen was modeled as a two-dimensional honeycomb-like
      structure made up of an array of hexagonal cells. Each trabecula was modeled as a
      linearly elastic beam element with the same material properties as cortical bone.
      Initial microcracks were assumed to exist within the oblique trabeculae and to
      grow according to the Paris law. Forces and moments were computed in each
      trabecula and the microcracks were allowed to propagate until fracture occurred.
      Between cycles, fractured trabeculae were removed from the finite element mesh,
      and force and moment distributions were calculated for the next cycle. This
      iterative process was continued until the simulated trabecular bone specimen
      showed a 10% reduction in modulus. Creep failure was also studied using a single
      cell analysis, in which a closed-form solution was obtained after prescribing the
      creep properties of the trabeculae. The results of the crack propagation analysis
      showed that fractures of only a small number of individual trabeculae can cause a
      substantial reduction in the modulus of the trabecular bone specimen model.
      Statistical tests were performed to compare the slopes and intercepts of the S-N
      curves of our model predictions to those of experimentally derived S-N curves for
      bovine trabecular bone. There was no significant difference (p > 0.2 for both
      slope and intercept) between our model predictions and the experimentally derived
      S-N curves for the low-stress, high-cycle range. For the high-stress, low-cycle
      range, the crack propagation model overestimated the fatigue life for a given
      stress level (for slope, p < 0.001), while the creep analysis agreed well with
      the experimental data (for slope, p > 0.2). These findings suggest that the
      primary failure mechanism for low-stress, high-cycle fatigue of trabecular bone
      is crack growth and propagation, while the primary failure mechanism for high
      stress, low-cycle fatigue is creep deformation and fracture. Furthermore, our
      results suggest that the modulus of trabecular bone at the specimen level may be
      highly sensitive to fractures of individual trabeculae.

PMID- 8132684
TI  - Estimated mean flow resistance increase during coronary artery catheterization.
AB  - The purpose of this investigation is to examine the influence of the presence and
      size of the catheter on the measurement of mean pressure drop and, thus, flow
      resistance in coronary vessels. Relatively large mean translesional pressure
      gradients have been reported, but they may be due to obstruction effects. To
      evaluate this hypothesis, analytical flow modeling coupled with in vitro
      experimental evidence was used to estimate mean flow resistance increases due to
      the presence of a catheter in a proximal vessel for concentric and eccentric
      catheter configurations. For an angioplasty catheter, over the relative range of
      catheter size to coronary vessel size (di/d(o)) from 0.3 to 0.7 (which is
      currently being used clinically), the flow resistance increased by a large factor
      of 3-33 for the concentric configuration. For smaller infusion catheters, the
      flow resistance increase was less, although still appreciable. Very small
      angioplasty guidewire also leads to sizeable increases in flow resistance.
      Effects of catheter eccentricity also indicated substantial increases in flow
      resistance, although the magnitude was less. These initial results might be used
      by clinicians to obtain rough estimates of actual mean pressure gradients in vivo
      in relatively straight proximal segments of artery from values measured with
      catheters. Since catheters are used so widely clinically, these initial results
      may be useful also for other vessels in the vascular system where the mean flow
      is describable by the Poiseuille relation. Whereas there is reasonable confidence
      in the flow modeling methodology, hemodynamic data are needed to evaluate the
      actual magnitude of the effects of obstruction in vivo.

PMID- 8132683
TI  - Quantitative interpretation of lumbar muscle myoelectric signals during rapid
      cyclic attempted trunk flexions and extensions.
AB  - The quantitative relationship between lumbar myoelectric signals (MES) and
      rapidly varying isometric trunk muscle forces was investigated. Ten young adult
      males were asked to cycle harmonically between attempted trunk flexion and
      attempted trunk extension in an upright position at rates of 0.33, 0.67 and 1.0
      Hz to peak efforts of 20, 40 and 60% of maximum voluntary exertion levels. The
      forces voluntarily exerted against a load cell were measured and used along with
      acquired kinematic data to calculate the time course of the net sagittal moment
      at the level of the third lumbar vertebra during task performances. A 22 muscle
      double linear programming biomechanical model was used to predict the lumbar
      trunk muscle contraction forces from the calculated moments. Rectified and
      bidirectionally low-pass filtered myoelectric activities were acquired at the L3
      level from four abdominal muscles and four back muscles. The processed MES were
      found to be well correlated (r > 0.90) with predicted muscle forces when the MES
      were time-shifted to account for electromechanical delay as well as the dynamic
      phase shift between muscle electrical activity and contraction force. Mean time
      shifts that maximized the linear MES-force relationship ranged from 111 to 218
      ms, were greater for the trunk extensors than the trunk flexors and generally
      exhibited lateral symmetry. The corresponding approximate phase angles averaged
      20 degrees at the slowest rate and 50 degrees at the fastest rate. MES-force
      phase angles decreased as effort level was increased indicating that the dynamic
      MES-force relationship is nonlinear. These results illustrate the importance of
      accounting for the phase lag between muscle electrical activity and force when
      using MES to quantify muscle loads during rapidly varying exertions.

PMID- 8132685
TI  - Three-dimensional simulations of the scoliosis derotation maneuver with Cotrel
      Dubousset instrumentation.
AB  - The derotation maneuver using Cotrel-Dubousset instrumentation (CDI) is intended
      to correct the counterdirectional transverse plane rotations of the spine and of
      the vertebrae in thoracic scoliosis. This was simulated in a finite element model
      of an idealized thoracic scoliosis with an initial 65 degrees scoliosis angle and
      0 degree kyphosis angle. After 90 degrees of rod rotation the apical vertebra
      derotated 50 degrees towards the sagittal plane but the apical vertebra axial
      rotation worsened by 8 degrees. The scoliosis angle corrected to 29 degrees and a
      54 degrees kyphosis was created. If the initial rod curvature was reduced by 9
      degrees, the model predicted only small changes in spinal curvature resulting
      from the forces required to connect the vertebrae to the hooks. Decreased
      kyphosis and scoliosis curvatures but increased vertebra axial rotation were
      produced by the derotation maneuver. The increase in apical vertebra axial
      rotation was reversed by modifying the representation of the motion segments by
      repositioning their effective axes 30 mm posteriorly.

PMID- 8132686
TI  - On the sufficiency conditions for the stability of bone remodeling equilibrium.
AB  - In this technical note a sufficiency condition is established for the stability
      of a strain-energy-based bone remodeling theory in the special case of a beam
      loaded by an axial force and a bending moment. In a previous report the same
      condition was shown to be a necessary condition for stability in the same
      situation. The remodeling scheme is one characterized by a remodeling stimulus
      equal to the strain energy density divided by the bulk or apparent density raised
      to an exponent m as well an elastic modulus proportional to bulk or apparent
      density raised to an exponent n. In order for a remodeling scheme to be stable
      for an elastic beam loaded by an axial force and a bending moment, it is
      established that the condition that m must be greater than n is not only
      necessary, but also sufficient.

PMID- 8132687
TI  - Finite element analysis of cerebral contusion.
AB  - Finite element analysis was carried out to study the mechanism of cerebral
      contusion. Clinical findings indicate that most cerebral contusions in the
      absence of skull fracture occur at the frontal and temporal lobes. To explain
      these observations, cavitation and shear strain theories have long been
      advocated. Plane strain finite element models of a parasagittal section of the
      human head were developed in the present study. The model was first validated
      against a set of experimental results from the literature. Frontal and occipital
      impacts were then simulated, and pressure and shear stress distributions in the
      brain were compared. While comparable negative pressures always developed in the
      contrecoup regions, shear stress distributions remained nearly identical
      regardless of the impact direction, consistent with the clinically observed
      pattern for contusion. Therefore, shear strain theory appears to account better
      for the clinical findings in cerebral contusion.

PMID- 8132688
TI  - Static circumferential tangential modulus of human atherosclerotic tissue.
AB  - The mechanical properties of atherosclerotic plaque may be of critical importance
      to the processes of plaque rupture, the most common antecedent of myocardial
      infarction. To investigate the effects of plaque structure and applied tensile
      stress on the static circumferential tangential modulus of atherosclerotic
      plaque, the stress-strain behavior of 26 human aortic intimal plaques was
      studied. Intimal plaques were collected during routine autopsies of 21 patients
      from the abdominal (n = 19) and thoracic (n = 2) aorta and were classified by
      histological analysis as cellular (n = 12), hypocellular (n = 9), and calcified
      (n = 5). At a physiologic applied circumferential tensile stress of 25 kPa, the
      tangential moduli of cellular, hypocellular, and calcified specimens were 927 +/-
      468 kPa, 2312 +/- 2180 kPa, and 1466 +/- 1284 kPa, respectively. There was a
      nonsignificant difference in tangential modulus at 25 kPa stress between
      specimens classified as cellular and hypocellular (p = 0.098), cellular and
      calcified (p = 0.410), and hypocellular and calcified (p = 0.380). This is in
      marked contrast to the previously measured radial compressive behavior of plaque
      tissue, which showed that cellular, hypocellular, and calcified plaques were
      significantly different in their modulus. In tension, all 26 plaques tested
      demonstrated a statistically significant increase in tangential modulus with
      increasing applied circumferential stress. We conclude that the static
      circumferential tangential modulus of atherosclerotic plaque, unlike its radial
      compressive modulus, is not significantly affected by the degree of cellularity
      and calcification determined by histological characterization.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8132689
TI  - On optimal velocity during cycling.
AB  - This paper focuses on the solution of two problems related to cycling. One is to
      determine the velocity as a function of distance which minimizes the cyclist's
      energy expenditure in covering a given distance in a set time. The other is to
      determine the velocity as a function of the distance which minimizes time for
      fixed energy expenditure. To solve these problems, an equation of motion for the
      cyclist riding over arbitrary terrain is written using Newton's second law. This
      equation is used to evaluate either energy expenditure or time, and the
      minimization problems are solved using an optimal control formulation in
      conjunction with the method of Miele [Optimization Techniques with Applications
      to Aerospace Systems, pp. 69-98 (1962) Academic Press, New York]. Solutions to
      both optimal control problems are the same. The solutions are illustrated through
      two examples. In one example where the relative wind velocity is zero, the
      optimal cruising velocity is constant regardless of terrain. In the second, where
      the relative wind velocity fluctuates, the optimal cruising velocity varies.

PMID- 8132690
TI  - The nature of the stabilizing functions of skeletal muscles.
AB  - The paper defines the term coordination interval (CI), suggesting that it should
      replace the term electromechanical delay (EMD), if this parameter is determined
      in vivo for a muscle functioning in a biomechanical system with considerable
      mobility, but not in a kinematic pair with one degree of rotational freedom
      (DOF). It was adopted that CI is the time elapsing between the moment of exertion
      of the resultant muscular force to the surroundings by the ending of the
      biokinematic chain with many DOFs, and the onset of myopotential in the muscle
      involved in its actuation. Tested at the same time was the utility efficiency of
      the system: man--unstable external object with adjustable mobility, as well as
      the participation and coordination patterns of the upper extremity muscles
      engaged in stabilizing and motor activities. Twelve adult men, students of
      physical education, took part in the experiment. The experimental set-up was in
      the form of a 3.08 m long physical pendulum with the inertial moment of 574 kg m2
      and with an exchangeable ending that served as a handle. Three endings were used
      with zero, one or two DOFs in relation to the pendulum shaft. The subjects of the
      test were told to push the pendulum ending with maximum force using the upper
      extremity, so as to impart to it the highest possible kinetic energy,
      irrespective of its stability type and mobility. The muscles straightening the
      upper extremity and stabilizing the wrist joint were tested in the EMG
      measurements. As a result of the experiment, it was found that (1) the utility
      efficiency of the organism in relation to the force and muscular power exerted on
      the surroundings decreases to 80 and 60%, respectively, if a driven object
      requires stabilization, and (2) the patterns of muscular synergism expressed by
      sequences and frequencies of muscular activation by the nervous system, on the
      grounds of CI, undergo characteristic changes if a driven object becomes
      unstable.

PMID- 8132691
TI  - A method for inducing equi-biaxial and uniform strains in elastomeric membranes
      used as cell substrates.
AB  - A device is described which is designed to bring about uniform and equi-biaxial
      strains of 0.04-0.4% on a circular elastomeric sheet upon which cells are grown
      in a monolayer. Strain measurements at six different radii of the well provide
      evidence of the uniformity of the strain field over the 2.54 cm diameter of the
      well with a mean strain of 0.15% and a standard deviation of 0.01% strain. Major
      advantages of the system over those previously described are that (1) the
      substrate remains in the same plane throughout the application of stretch, (2)
      the device is designed to provide a state of uniform equi-biaxial strain to the
      entire substrate of the cells and (3) all cells 'see' the same strain field, no
      matter what their orientation. This allows for real-time optical monitoring of
      the cells throughout the stretching cycle of the cell substrate. In this way,
      changes in the cell membrane, cell nucleus, cytoskeleton and in fluorescently
      labelled calcium can be monitored microscopically during application of an equi
      biaxial mechanical stretch.

PMID- 8132692
TI  - A six-degree-of-freedom transducer for in vitro measurement of patellofemoral
      contact forces.
AB  - A satisfactory design of the patellar component used in total knee arthroplasty
      and a general understanding of the effects of orthopedic procedures require, in
      part, an accurate description of patellofemoral contact forces. Experimental
      determination of the contact stress distribution requires integration to estimate
      the contact forces. Due to complex patellar geometry, the determination of the
      components of the resultant load is difficult. Current techniques for the direct
      measurement of contact loads either report a single load component or require
      sequential experiments to fully describe the contact force. The present study
      describes the development of a six-degree-of-freedom patellofemoral force
      transducer. This transducer allows the simultaneous determination of the three
      components of the contact force with an increase in accuracy over available
      devices. The contact forces components are accurate to 1% of full scale (900 N
      anterior-posterior, +/- 200 N medial-lateral and inferior-superior). The location
      on the patella where the resultant force acts is determined to within 1 mm.
      Relative movement of this point as a function of either normal change in knee
      flexion angle or as a result of a typical orthopedic procedure is determined to
      within 0.1 mm. A protocol is presented that allows the contact forces to be
      determined for either the anatomically normal patella or a patella following
      total knee arthroplasty.

PMID- 8132693
TI  - A new attempt at the interpretation of the functional architecture of the
      cancellous bone.
AB  - The author's theory explains the development mechanisms of the functional
      structure of cancellous bone. Functional, secondary cancellous bone develops from
      the primary growth-dependent cancellous lattice under the influence of
      multidirectional loading. The primary cancellous bone is remodelled according to
      the general strain-dependent mechanism of the functional adaptation of bone.
      Oblique loading of the metaphysis in extreme positions in the joint evokes the
      greatest strain in the bone trabeculae oriented in these oblique directions, as
      demonstrated by calculation on a simple three-beam model. All trabeculae are
      therefore remodelled in these directions resulting in a typical picture of two
      crossed pressure systems. Each of them corresponds to one of the extreme loading
      directions. Tensile systems can be found only in places of ligament or tendon
      insertions or under concave joint surfaces.

PMID- 8132694
TI  - The effects of coumarin and suramin on the growth of malignant renal and
      prostatic cell lines.
AB  - Coumarin is known to exert an anti-neoplastic action in patients with malignant
      melanoma and renal cell carcinoma. We examined the effects of various
      concentrations (0, 10, 50, 100, 250, 500 micrograms/ml) of coumarin on the
      proliferation of two renal cell carcinoma cell lines (786-O and A-498) and two
      malignant prostatic cell lines (DU145 and LNCaP). After 5 days of treatment,
      coumarin inhibited the growth of the four cell lines. The LNCaP prostatic cell
      line was more sensitive than the other cell lines to the inhibitory effects of
      coumarin. We also examined the effects of various concentrations of suramin (0,
      50, 200 and 400 micrograms/ml), and anti-neoplastic compound currently undergoing
      clinical trials, on the growth of the 786-O and LNCaP cell lines. Both of these
      were inhibited by suramin at concentrations greater than 100 micrograms/ml.
      Finally we examined the effects of combined treatment with coumarin and suramin
      on the growth of LNCaP and 786-O cells. When combined with all concentrations of
      suramin studied (0, 50, 200 and 400 micrograms/ml), coumarin further inhibited
      cellular proliferation of the LNCaP and 786-O cell lines. However, the
      combination of the highest concentration of coumarin (500 micrograms/ml) with
      suramin at 400 micrograms/ml did not inhibit the proliferation of the cells more
      than 500 micrograms/ml coumarin alone.

PMID- 8132695
TI  - Antitumour activity of coumarin in prostate and mammary cancer models.
AB  - The antineoplastic and antimetastatic activities of coumarin were evaluated in
      transplanted prostate tumours of the rat. The growth of Noble Nb-R prostate
      tumours was strongly inhibited by coumarin (40 mg/kg; administered three times
      per week), whereas the hormonally more sensitive Dunning R3327-G rat prostate
      carcinoma did not respond. Coumarin was also shown to possess antimetastatic
      activity in a Dunning R3327-MatLu tumour model. The number of lung metastases was
      reduced significantly by 40%-50% following the administration of coumarin (40 mg
      daily). Preliminary data from experiments with rats bearing DMBA-induced mammary
      carcinomas showed that these tumours are as sensitive to coumarin as Noble-R
      prostate tumours.

PMID- 8132696
TI  - Mode of action of coumarin in immune cells.
AB  - In order to characterize further the mode of action of coumarin, binding studies
      were undertaken using human monocytes and radioactively labelled drug. Since
      coumarin is only a small compound and we wanted to exclude possible artefacts due
      to variations in size or conformation, the drug was produced by synthesis in the
      presence of radioactive 14C. Adding increasing amounts of a mixture of labelled
      and unlabelled drug to monocytes resulted in saturating conditions only at rather
      high concentrations. Performing Scatchard analysis demonstrated that binding
      sites for coumarin appeared to be present in relatively high numbers (7.5 x
      10(8)/cell) but their affinity was rather low (K alpha approximately 2 x 10(2) M
      1). Inhibition studies with 7-hydroxycoumarin revealed that an approximately four
      times higher molar concentration of the derivative was necessary to cause 50%
      displacement of coumarin from its binding site. These results indicate that
      binding of the drug to cells is characterized by high-capacity but low-affinity
      conditions. This would be compatible with the hypothesis that coumarin interacts
      with ubiquitous intracellular receptor proteins able to interact with aromatic
      hydrocarbons, which might form the basis for enzyme induction, and leads to the
      effects observed in vitro and in vivo.

PMID- 8132697
TI  - Coumarin modulates the cell-cycle progression of an MTV-EJras cell line.
AB  - The effects of coumarin (1,2-benzopyrone) on ras oncogene expression during the
      cell cycle of an MTV-EJras cell line was determined by flow cytometry. ras
      oncogene expression in cells was induced by dexamethasone and increased fivefold
      during G1/G0 phase and threefold in S phase. Dexamethasone also increased the
      percentage of cells in S phase from 21% to 31%, compared to phosphate-buffered
      saline-treated control cells (P < 0.01). Coumarin decreased the percentage of
      dexamethasone-treated cells in S phase from 31% to 19%, with a concomitant
      increase in the percentage of cells in G1/G0 compared to control levels. Coumarin
      also reduced ras expression (mean fluorescence) by 40% in G1/G0 phase and 30% in
      S phase. We conclude that coumarin significantly reduces the cell-cycle
      progression of MTV-EJras cells and decreases ras expression in both G1 and S
      phases. These findings suggest a novel approach to the selective control of
      proliferation of malignant cells.

PMID- 8132698
TI  - 7-Hydroxycoumarin inhibits oncogene-induced transformation of murine fibroblasts.
AB  - 7-Hydroxycoumarin (7-HC) is a naturally occurring substance with a variety of
      biological activities, e.g. antitumoral and immunomodulatory action. The
      potential mechanisms of 7-HC action on tumor cells have been investigated in a
      model of mouse fibroblasts transformed by distinct retroviral vectors carrying
      the oncogenes myc and ras. Treatment of the different oncogenic transformants
      with 7-HC in non-cytotoxic concentrations causes a strong inhibition of their
      proliferative capacity as measured by growth curves. Furthermore, incubation of
      the ras and myc transformants with 7-HC abrogated soft agar colony formation when
      compared to untreated cultures. These changes in cell growth characteristics of
      the various oncogene-transformed mouse fibroblasts were transient, since removal
      of 7-HC from the cultures caused a reappearance of the transformed properties of
      these cells within 6 days. The 7-HC-mediated inhibition of the proliferative
      capacity of the transformants was preceded by a selective down-regulation of
      oncogene expression. These data suggest that 7-HC causes a reversible inhibition
      of ras- and myc-induced neoplastic properties in transformed fibroblasts by
      selective down-regulation of retroviral RNA levels.

PMID- 8132699
TI  - Antibody-based approaches to coumarin analysis.
AB  - 7-Hydroxycoumarin (7-HC) was chemically conjugated by diazo coupling to carrier
      proteins such as bovine serum albumin (BSA), thyroglobulin and ovalbumin. These
      conjugates were characterised by sodium dodecyl sulphate/polyacrylamide gel
      electrophoresis (SDS-PAGE) and high-performance liquid chromatography (HPLC).
      Rabbits were immunised using the 7-HC-BSA conjugate. The highest antibody titre
      achieved was 1:10,000, as determined by competitive enzyme-linked immunosorbent
      assay (ELISA). The resulting antibodies were purified by ammonium sulphate
      precipitation, followed by protein A affinity chromatography. Their purity was
      assessed by SDS-PAGE and HPLC. These antibodies have been used in the development
      of a competitive ELISA, an amperometric biosensor and an electrochemical
      immunoassay. Both the ELISA and amperometric biosensor have been successfully
      applied to the analysis of 7-HC and its glucuronide conjugate in human urine
      samples. Each of these antibody-based methods provides a novel approach to the
      analysis of the main metabolites of coumarin.

PMID- 8132700
TI  - Regulation of coumarin 7-hydroxylation in man.

PMID- 8132701
TI  - Treatment with coumarin to prevent or delay recurrence of malignant melanoma.
AB  - Both coumarin (1,2-benzopyrone) and warfarin (4-hydroxycoumarin) have been shown
      to prevent the recurrence of malignant melanoma. Their action is macrophage
      dependent and the dosage is critical. In 1984 a multicentre, prospective,
      randomised, double-blind trial of coumarin, given as a daily 50-mg dose for 2
      years after surgery in patients with high-risk melanoma, was started. the
      patients had lesions greater than 1.70 mm thick and TNM stage IB or stage II
      disease. To date there are 4 recurrences in the coumarin-treated group of 13
      patients, and 10 recurrences in the placebo-treated group of 14 patients (P <
      0.01). There were no toxic effects.

PMID- 8132702
TI  - Coumarin (1,2-benzopyrone) for the treatment of prostatic carcinoma.
AB  - The unavailability of effective treatment for metastatic hormone-refractory and
      clinically localized but pathologically unfavorable prostatic carcinoma warrants
      trial of new and promising treatments. Preliminary studies in patients with
      metastatic disease have shown (a) subjective but no objective responses to 100 mg
      coumarin and cimetidine daily; (b) objective responses in 3 of 40 patients
      treated with 3 g coumarin daily, all of whom had normal performance status and 1
      of whom remains with three resolved bone metastases and stable prostate-specific
      antigen levels after 4 years; (c) toxicity only in bedridden patients. We
      recently initiated two multi-center trials of 1 g coumarin daily. Metastatic
      prostatic carcinoma patients of normal performance status were treated in a phase
      II trial. Patients who had been treated by radical prostatectomy, but had
      surgical margin, seminal vesicle or lymph node involvement or detectable prostate
      specific antigen after radical prostatectomy, were randomized to coumarin or
      placebo.

PMID- 8132703
TI  - An updated review of the clinical development of coumarin (1,2-benzopyrone) and 7
      hydroxycoumarin.
AB  - Several authors have demonstrated that coumarin (1,2-benzopyrone) in combination
      with cimetidine can produce objective antitumor responses in some patients with
      advanced renal cell carcinoma. The purpose of this report is to review the
      clinical development of coumarin, with or without cimetidine, with special
      reference to renal cell carcinoma (RCC). Previously unpublished data concerning
      the survival of a population of patients with RCC, who were treated on a phase I
      trial of coumarin and cimetidine, are presented. The rationale and study design
      of an active randomized, double-blinded, placebo-controlled trial of coumarin for
      RCC are discussed. A progress report is given for an ongoing phase I trial of
      oral 7-hydroxycoumarin, the major human metabolite of coumarin.

PMID- 8132704
TI  - Satellite cell proliferation in the adult rat trigeminal ganglion results from
      the release of a mitogenic protein from explanted sensory neurons.
AB  - Explant of trigeminal ganglia neurons in adult rats induces perineuronal glial
      proliferation of primarily satellite cells as opposed to Schwann cells. This
      proliferation begins at 15 h after explant culture and by 27 h there is a
      significant increase in glial proliferation as measured by scintillation counts
      of [3H]thymidine. Blocking protein synthesis between 0 and 3.5 h after explant
      culture (early) results in an enhanced proliferative response, while blocking
      protein synthesis between 3.5 and 7 h (late) causes a complete block of the
      proliferative response assessed at 27 h. Conditioned media experiments
      demonstrate that both the mitogenic and inhibitory signals are diffusible and
      heat labile. Finally, the addition of neurotrophic factors to rescue injured
      ganglionic neurons attenuates the proliferative glial response suggesting that
      injured neurons produce and release signals that induce glial proliferation.

PMID- 8132705
TI  - NIH3T3 cells expressing the deleted in colorectal cancer tumor suppressor gene
      product stimulate neurite outgrowth in rat PC12 pheochromocytoma cells.
AB  - The Deleted in Colorectal Cancer (DCC) gene is a candidate tumor suppressor gene
      that is predicted to encode a transmembrane polypeptide with strong similarity to
      the neural cell adhesion molecule (N-CAM) family. Previous studies have suggested
      that several different N-CAMs, when expressed in non-neuronal cell types can
      stimulate neurite outgrowth from PC12 rat pheochromocytoma cells. Based on the
      predicted structural similarity of DCC to N-CAMs, we sought to determine whether
      NIH3T3 cells expressing DCC could stimulate neurite outgrowth in PC12 cells. We
      found that NIH3T3 cell lines expressing DCC could stimulate PC12 cells to extend
      neurites. Supernatants from DCC-transfected NIH3T3 cells did not induce neurite
      outgrowth above background levels, suggesting that cell-cell interaction was
      required. NIH3T3 cells expressing a truncated form of DCC, lacking the majority
      of the cytoplasmic domain sequences, also failed to induce neurite outgrowth
      above the levels seen with control NIH3T3 cells, suggesting that the cytoplasmic
      domain of DCC was necessary for its neurite-promoting function. In contrast to
      NGF-mediated neurite outgrowth, the DCC-mediated response was inhibited by
      treatment with pertussis toxin or the combination of N- and L-type calcium
      channel blockers, and was unaffected by the transcriptional inhibitor cordycepin.
      The data suggest that the DCC protein can function in a fashion analogous to
      other N-CAMs to alter PC12 cell phenotype through intracellular pathways distinct
      from those involved in NGF signaling.

PMID- 8132706
TI  - Tyrosine kinase inhibitors can differentially inhibit integrin-dependent and CAM
      stimulated neurite outgrowth.
AB  - We have used monolayers of parental 3T3 cells and 3T3 cells expressing one of
      three transfected cell adhesion molecules (CAMs) (NCAM, N-cadherin, and L1) as a
      culture substrate for rat cerebellar neurons. A number of tyrosine kinase
      inhibitors have been tested for their ability to inhibit neurite outgrowth over
      parental 3T3 monolayers which we show to be partly dependent on neuronal integrin
      receptor function, as compared with neurite outgrowth stimulated by the above
      three CAMs. Whereas genistein (100 microM), lavendustin A (20 microM), and
      tyrphostins 34 and 47 (both at 150 microM) had no effect on integrin dependent or
      CAM stimulated neurite outgrowth, the erbstatin analogue (10-15 micrograms/ml)
      and tyrphostins 23 and 25 (both at 150 microM) specifically inhibited the
      response stimulated by all three CAMs. CAM stimulated neurite outgrowth can be
      accounted for by a G-protein-dependent activation of neuronal calcium channels;
      experiments with agents that directly activate this pathway localized the
      erbstatin analogue site of action upstream of the G-protein and calcium channels,
      whereas tyrphostins have sites of action downstream from calcium channel
      activation. These data suggest that activation of an erbstatin sensitive tyrosine
      kinase is an important step upstream of calcium channel activation in the second
      messenger pathway underlying the neurite outgrowth response stimulated by a
      variety of CAMs, and that this kinase is not required for integrin-dependent
      neurite outgrowth.

PMID- 8132707
TI  - Novel N-glycosylation in eukaryotes: laminin contains the linkage unit beta
      glucosylasparagine.
AB  - The linkage unit to protein of N-linked carbohydrate in eukaryotic glycoproteins
      consists of N-acetylglucosamine, coupled to the amido nitrogen of asparagine.
      Additional N-glycosyl linkage units have been unequivocally proven to exist only
      in the cell surface glycoproteins of various bacteria. Based on immunological
      analyses, isolation and chemical characterization, we report that one of these
      units, namely glucose linked to asparagine, exists in the mammalian protein
      laminin, an extracellular basement membrane component. This finding and the
      occurrence of identical disaccharide structures in archaebacterial cell surface
      glycoproteins and mammalian basement membrane protein complexes points towards a
      conserved and distinct function of these extracellular structural elements. In
      addition, a method is described to uncover a masked epitope in fixed tissues by
      chemical O-deglycosylation. This has allowed to morphologically localize the
      antigen beta-Glc-Asn by immunofluorescence to the basement membranes of kidney
      glomeruli.

PMID- 8132708
TI  - A novel laminin E8 cell adhesion site required for lung alveolar formation in
      vitro.
AB  - Basement membrane-adherent type II alveolar cells isolated from lung assemble
      into lumen-containing cellular spheres which retain the correct polarity and
      thereby approximate the earliest fetal stage of alveolar morphogenesis. The
      molecular basis of this process, determined in initial experiments to be
      attributable mainly to the large heterotrimeric glycoprotein laminin, was probed
      with laminin proteolytic fragments, antibodies, and synthetic peptides. The
      carboxy-terminal fragment E8, but not equimolar amounts of fragment P1, blocked
      alveolar formation. To pursue this observation, we used several anti-E8
      antibodies and identified one, prepared against A chain residues 2179-2198 ("SN
      peptide") from the first loop of the G domain, as inhibitory. These results were
      confirmed by use of SN-peptide alone and further defined by trypsin digestion of
      SN-peptide to the sequence SINNNR. This conserved site promoted divalent cation
      dependent adhesion of both type II alveolar and HT1080 cells, was inhibitable
      with equimolar amounts of fragment E8 but not P1, and derives from a form of
      laminin present in fetal alveolar basement membranes. These studies point to an
      important novel cell adhesion site in the laminin E8 region with a key role in
      lung alveolar morphogenesis.

PMID- 8132709
TI  - High expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast
      lineage during mouse development.
AB  - cDNA clones for murine 92 kD type IV collagenase (gelatinase B) were generated
      for the determination of its primary structure and for analysis of temporal and
      spatial expression in vivo. The mouse enzyme has 72% sequence identity with the
      human counterpart, the major difference being the presence of a 16-residue
      segment absent from the human enzyme. In situ hybridization analyses of embryonic
      and postnatal mouse tissues revealed intense signals in cells of the osteoclast
      cell lineage. Clear expression above background was not observed in macrophages,
      polymorphonuclear leukocytes, monocytes, or epithelial cells which have been
      shown to express the gene in vitro in cell cultures. Expression of the gene was
      first observed at early stage of cartilage and tooth development at E13, where
      signals were seen transiently in surrounding mesenchymal cells. At later
      developmental stages and postnatally strong expression was seen in large cells at
      the surface of bones. These cells were presumably osteoclasts as their location
      correlated with that of TRAP positive cells. Signals above background were not
      observed in a number of other tissues studied. The results represent the first
      demonstration of a highly osteoclast specific extracellular proteinase. The
      results suggest that during normal development of embryonic organs the 92-kD type
      IV collagenase does not have a major role in basement membrane degradation, but
      is rather mainly used for the turnover of bone matrix, possibly as a gelatinase
      required for the removal of denatured collagen fragments (gelatin) generated by
      interstitial collagenase.

PMID- 8132710
TI  - En bloc incorporation of coatomer subunits during the assembly of COP-coated
      vesicles.
AB  - The cDNA encoding epsilon-COP, the 36-kD subunit of coatomer, was cloned from a
      bovine liver cDNA library and sequenced. Immunoblotting with an anti-epsilon-COP
      antibody showed that epsilon-COP exists in COP-coated vesicles as well as in the
      cytosolic coatomer. Using the cloned cDNA, recombinant His6- tagged epsilon-COP
      was overexpressed in cultured Chinese hamster ovary (CHO) cells, from which
      metabolically radiolabeled coatomer was purified by taking advantage of the His6
      tag. Radiolabeled coatomer was employed to establish that all the subunits of the
      coatomer enter coated vesicles as an intact unit.

PMID- 8132711
TI  - Evidence for defects in membrane traffic in Paramecium secretory mutants unable
      to produce functional storage granules.
AB  - The ciliated protozoan Paramecium has a regulated secretory system amenable to
      genetic analysis. The secretory storage granules, known as trichocysts, enclose a
      crystalline matrix with a genetically determined shape whose biogenesis involves
      proteolytic maturation of a family of precursor molecules into a heterogeneous
      set of small acidic polypeptides that crystallize within the maturing vesicles.
      We have developed an original pulse-chase protocol for monoxenic Paramecium
      cultures using radiolabeled bacteria to study the processing of trichocyst matrix
      proteins in wild-type and mutant cells. In wild-type cells, proteolytic
      processing is blocked in the presence of monensin and otherwise rapidly completed
      after approximately 20 min of chase, suggesting that the conversion occurs in the
      trans-Golgi and/or in small vesicles soon after sorting to the regulated pathway,
      probably before crystallization begins. In trichless mutant cells, which contain
      no visible trichocysts, secretory proteins are synthesized but not processed and
      we report constitutive secretion of the uncleaved precursor molecules. The
      mutation thus appears to affect sorting to the regulated pathway and should prove
      useful for analysis of the sorting machinery and of the relationship between
      sorting and proteolytic processing of secretory proteins. In mutants bearing
      misshapen trichocysts with poorly crystallized contents (tam33, tam38, stubbyA),
      the proteolytic processing of the trichocyst matrix proteins appears to be
      normal, while both pulse-chase and morphological data indicate that intracellular
      transport is perturbed, probably between ER and Golgi. Precursor molecules are
      present in the mutant trichocysts but not in wild-type trichocysts and may
      account for the defective crystallization. Our analysis of these mutants suggests
      that the temporal coordination of intracellular traffic plays a regulatory role
      in granule maturation.

PMID- 8132712
TI  - Ultrastructural analysis of the autophagic process in yeast: detection of
      autophagosomes and their characterization.
AB  - Under nutrient-deficient conditions, the yeast S. cerevisiae sequesters its own
      cytoplasmic components into vacuoles in the form of "autophagic bodies"
      (Takeshige, K., M. Baba, S. Tsuboi, T. Noda, and Y. Ohsumi. 1992. J. Cell Biol.
      119:301-311). Immunoelectron microscopy showed that two cytosolic marker enzymes,
      alcohol dehydrogenase and phosphoglycerate kinase, are present in the autophagic
      bodies at the same densities as in the cytosol, but are not present in vacuolar
      sap, suggesting that cytosolic enzymes are also taken up into the autophagic
      bodies. To understand this process, we performed morphological analyses by
      transmission and immunological electron microscopies using a freeze-substitution
      fixation method. Spherical structures completely enclosed in a double membrane
      were found near the vacuoles of protease-deficient mutant cells when the cells
      were shifted to nutrient-starvation media. Their size, membrane thickness, and
      contents of double membrane-structures corresponded well with those of autophagic
      bodies. Sometimes these double membrane structures were found to be in contact
      with the vacuolar membrane. Furthermore their outer membrane was occasionally
      seen to be continuous with the vacuolar membrane. Histochemical staining of
      carbohydrate strongly suggested that the structures with double membranes fused
      with the vacuoles. These results indicated that these structures are precursors
      of autophagic bodies, "autophagosomes" in yeast. All the data obtained suggested
      that the autophagic process in yeast is essentially similar to that of the
      lysosomal system in mammalian cells.

PMID- 8132713
TI  - An internal region of the peroxisomal membrane protein PMP47 is essential for
      sorting to peroxisomes.
AB  - Targeting sequences on peroxisomal membrane proteins have not yet been
      identified. We have attempted to find such a sequence within PMP47, a protein of
      the methylotrophic yeast, Candida boidinii. This protein of 423 amino acids shows
      sequence similarity with proteins in the family of mitochondrial carrier
      proteins. As such, it is predicted to have six membrane-spanning domains.
      Protease susceptibility experiments are consistent with a six-membrane-spanning
      model for PMP47, although the topology for the peroxisomal protein is inverted
      compared with the mitochondrial carrier proteins. PMP47 contains two potential
      peroxisomal targeting sequences (PTS1), an internal SKL (residues 320-322) and a
      carboxy terminal AKE (residues 421-423). Using a heterologous in vivo sorting
      system, we show that efficient sorting occurs in the absence of both sequences.
      Analysis of PMP47-dihydrofolate reductase (DHFR) fusion proteins revealed that
      amino acids 1-199 of PMP47, which contain the first three putative membrane
      spans, do not contain the necessary targeting information, whereas a fusion with
      amino acids 1-267, which contains five spans, is fully competent for sorting to
      peroxisomes. Similarly, a DHFR fusion construct containing residues 268-423 did
      not target to peroxisomes while residues 203-420 appeared to sort to that
      organelle, albeit at lower efficiency than the 1-267 construct. However, DHFR
      constructs containing only amino acids 185-267 or 203-267 of PMP47 were not found
      to be associated with peroxisomes. We conclude that amino acids 199-267 are
      necessary for peroxisomal targeting, although additional sequences may be
      required for efficient sorting to, or retention by, the organelles.

PMID- 8132714
TI  - Amino acid residues 24-31 but not palmitoylation of cysteines 30 and 45 are
      required for membrane anchoring of glutamic acid decarboxylase, GAD65.
AB  - The smaller isoform of the GABA synthesizing enzyme glutamic acid decarboxylase,
      GAD65, is synthesized as a soluble protein that undergoes post-translational
      modification(s) in the NH2-terminal region to become anchored to the membrane of
      small synaptic-like microvesicles in pancreatic beta cells, and synaptic vesicles
      in GABA-ergic neurons. A soluble hydrophilic form, a soluble hydrophobic form,
      and a hydrophobic firmly membrane-anchored form have been detected in beta cells.
      A reversible and hydroxylamine sensitive palmitoylation has been shown to
      distinguish the firmly membrane-anchored form from the soluble yet hydrophobic
      form, suggesting that palmitoylation of cysteines in the NH2-terminal region is
      involved in membrane anchoring. In this study we use site-directed mutagenesis to
      identify the first two cysteines in the NH2-terminal region, Cys 30 and Cys 45,
      as the sites of palmitoylation of the GAD65 molecule. Mutation of Cys 30 and Cys
      45 to Ala results in a loss of palmitoylation but does not significantly alter
      membrane association of GAD65 in COS-7 cells. Deletion of the first 23 amino
      acids at the NH2 terminus of the GAD65 30/45A mutant also does not affect the
      hydrophobicity and membrane anchoring of the GAD65 protein. However, deletion of
      an additional eight amino acids at the NH2 terminus results in a protein which is
      hydrophilic and cytosolic. The results suggest that amino acids 24-31 are
      required for hydrophobic modification and/or targeting of GAD65 to membrane
      compartments, whereas palmitoylation of Cys 30 and Cys 45 may rather serve to
      orient or fold the protein at synaptic vesicle membranes.

PMID- 8132715
TI  - A glycosylphosphatidylinositol (GPI)-negative phenotype produced in Leishmania
      major by GPI phospholipase C from Trypanosoma brucei: topography of two GPI
      pathways.
AB  - The major surface macromolecules of the protozoan parasite Leishmania major, gp63
      (a metalloprotease), and lipophosphoglycan (a polysaccharide), are
      glycosylphosphatidylinositol (GPI) anchored. We expressed a cytoplasmic
      glycosylphosphatidylinositol phospholipase C (GPI-PLC) in L. major in order to
      examine the topography of the protein-GPI and polysaccharide-GPI pathways. In L.
      major cells expressing GPI-PLC, cell-associated gp63 could not be detected in
      immunoblots. Pulse-chase analysis revealed that gp63 was secreted into the
      culture medium with a half-time of 5.5 h. Secreted gp63 lacked anti-cross
      reacting determinant epitopes, and was not metabolically labeled with
      [3H]ethanolamine, indicating that it never received a GPI anchor. Further, the
      quantity of putative protein-GPI intermediates decreased approximately 10-fold.
      In striking contrast, lipophosphoglycan levels were unaltered. However, GPI-PLC
      cleaved polysaccharide-GPI intermediates (glycoinositol phospholipids) in vitro.
      Thus, reactions specific to the polysaccharide-GPI pathway are compartmentalized
      in vivo within the endoplasmic reticulum, thereby sequestering polysaccharide-GPI
      intermediates from GPI-PLC cleavage. On the contrary, protein-GPI synthesis at
      least up to production of Man(1 alpha 6)Man(1 alpha 4)GlcN-(1 alpha 6)-myo
      inositol-1-phospholipid is cytosolic. To our knowledge this represents the first
      use of a catabolic enzyme in vivo to elucidate the topography of biosynthetic
      pathways. GPI-PLC causes a protein-GPI-negative phenotype in L. major, even when
      genes for GPI biosynthesis are functional. This phenotype is remarkably similar
      to that of some GPI mutants of mammalian cells: implications for paroxysmal
      nocturnal hemoglobinuria and Thy-1-negative T-lymphoma are discussed.

PMID- 8132717
TI  - Coupling of ATPase activity and motility in smooth muscle myosin is mediated by
      the regulatory light chain.
AB  - Smooth muscle myosin acts as a molecular motor only if the regulatory light chain
      (RLC) is phosphorylated. This subunit can be removed from myosin by a novel
      method involving the use of trifluoperazine. The motility of RLC-deficient myosin
      is very slow, but native properties are restored when RLC is rebound. Truncating
      6 residues from the COOH terminus of the RLC had no effect on phosphorylated
      myosin's motor properties, while removal of the last 12 residues reduced velocity
      by approximately 30%. Very slow movement was observed once 26 residues were
      deleted, or with myosin containing only the COOH-terminal RLC domain. These two
      mutants thus mimicked the behavior of RLC-deficient myosin, with the important
      difference that the mutant myosins were monodisperse when assayed by
      sedimentation velocity and electron microscopy. The decreased motility therefore
      cannot be caused by aggregation. A common feature of RLC-deficient myosin and the
      mutant myosins that moved actin slowly was an increased myosin ATPase compared
      with dephosphorylated myosin, and a lower actin-activated ATPase than obtained
      with phosphorylated myosin. These results suggest that the COOH-terminal portion
      of an intact RLC is involved in interactions that regulate myosin's "on-off"
      switch, both in terms of completely inhibiting and completely activating the
      molecule.

PMID- 8132716
TI  - Molecular characterization and tissue distribution of ZO-2, a tight junction
      protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor
      protein.
AB  - ZO-1 is a 210-225-kD peripheral membrane protein associated with cytoplasmic
      surfaces of the zonula occludens or tight junction. A 160-kD polypeptide,
      designated ZO-2, was found to coimmunoprecipitate with ZO-1 from MDCK cell
      extracts prepared under conditions which preserve protein associations (Gumbiner,
      B., T. Lowenkopf, and D. Apatira. 1991. Proc. Natl. Acad. Sci. USA. 88: 3460
      3464). We have isolated ZO-2 from MDCK cell monolayers by bulk
      coimmunoprecipitation with ZO-1 followed by electroelution from preparative SDS
      PAGE gel slices. Amino acid sequence information obtained from a ZO-2 tryptic
      fragment was used to isolate a partial cDNA clone from an MDCK library. The
      deduced amino acid sequence revealed that canine ZO-2 contains a region that is
      very similar to sequences in human and mouse ZO-1. This region includes both a 90
      amino acid repeat domain of unknown function and guanylate kinase-like domains
      which are shared among members of the family of proteins that includes ZO-1,
      erythrocyte p55, the product of the lethal(1)discs-large-1 (dlg) gene of
      Drosophila, and a synapse-associated protein from rat brain, PSD-95/SAP90. The
      dlg gene product has been shown to act as a tumor suppressor in the imaginal disc
      of the Drosophila larva, although the functions of other family members have not
      yet been defined. A polyclonal antiserum was raised against a unique region of ZO
      2 and found to exclusively label the cytoplasmic surfaces of tight junctions in
      MDCK plasma membrane preparations, indicating that ZO-2 is a tight junction
      associated protein. Immunohistochemical staining of frozen sections of whole
      tissue demonstrated that ZO-2 localized to the region of the tight junction in a
      number of epithelia, including liver, intestine, kidney, testis, and arterial
      endothelium, suggesting that this protein is a ubiquitous component of the tight
      junction. Double-label immunofluorescence microscopy performed on cryosections of
      heart, a nonepithelial tissue, revealed the presence of ZO-1 but no ZO-2 staining
      at the fascia adherens, a specialized junction of cardiac myocytes which has
      previously been shown to contain ZO-1 (Itoh, M., S. Yonemura, A. Nagafuchi, S.
      Tsukita, and Sh. Tsukita. 1991. J. Cell Biol. 115:1449-1462). Thus it appears
      that ZO-2 is not a component of the fascia adherens, and that unlike ZO-1, this
      protein is restricted to the epithelial tight junction.

PMID- 8132719
TI  - Intrinsic microtubule stability in interphase cells.
AB  - Interphase microtubule arrays are dynamic in intact cells under normal conditions
      and for this reason they are currently assumed to be composed of polymers that
      are intrinsically labile, with dynamics that correspond to the behavior of
      microtubules assembled in vitro from purified tubulin preparations. Here, we
      propose that this apparent lability is due to the activity of regulatory
      effectors that modify otherwise stable polymers in the living cell. We
      demonstrate that there is an intrinsic stability in the microtubule network in a
      variety of fibroblast and epithelial cells. In the absence of regulatory factors,
      fibroblast cell interphase microtubules are for the most part resistant to cold
      temperature exposure, to dilution-induced disassembly and to nocodazole-induced
      disassembly. In epithelial cells, microtubules are cold-labile, but otherwise
      similar in behavior to polymers observed in fibroblast cells. Factors that
      regulate stability of microtubules appear to include Ca2+ and the p34cdc2 protein
      kinase. Indeed, this kinase induced complete destabilization of microtubules when
      applied to lysed cells, while a variety of other protein kinases were
      ineffective. This suggests that p34cdc2, or a kinase of similar specificity, may
      phosphorylate and inactivate microtubule-associated proteins, thereby conferring
      lability to otherwise length-wise stabilized microtubules.

PMID- 8132720
TI  - Abnormal fibrillin assembly by dermal fibroblasts from two patients with Marfan
      syndrome.
AB  - The microfibrillar glycoprotein fibrillin is linked to the Marfan syndrome, an
      autosomal dominant connective tissue disorder. In this study, fibrillin
      synthesis, deposition and assembly has been investigated in Marfan dermal
      fibroblast lines from two unrelated patients for whom distinct mutations in the
      fibrillin gene FBN1 have been identified. In patient NB, a point mutation has
      occurred which causes an amino acid substitution and the other patient (GK) has a
      deletion in one allele. The two cell lines were broadly comparable with respect
      to de novo fibrillin synthesis and its distribution between medium and cell layer
      compartments. Electrophoresis of fibrillin immunoprecipitates confirmed the
      presence of fibrillin in medium and cell layers. GK cells secreted an additional
      higher relative molecular mass fibrillin-immunoreactive component. The time
      course of fibrillin secretion was similar for the two lines, but differences in
      fibrillin aggregation were apparent. Rotary shadowing electron microscopy of
      extracted cell layers demonstrated the presence of abundant and extensive
      microfibrils in NB cell layers. These were abnormal in their gross morphology in
      comparison to microfibrils isolated from control cultures. No periodic
      microfibrillar structures were isolated from GK cell layers. These studies
      underline the need to classify fibrillin defects in terms of biochemical and
      ultrastructural criteria. Examination of the effects of individual mutations on
      microfibril organization will be particularly informative in elucidating the
      relationship between microfibril dysfunction and the complex clinical
      manifestations of Marfan patients.

PMID- 8132718
TI  - Fluorescent actin analogs with a high affinity for profilin in vitro exhibit an
      enhanced gradient of assembly in living cells.
AB  - Constitutive centripetal transport of the actin-based cytoskeleton has been
      detected in cells spreading on a substrate, locomoting fibroblasts and
      keratocytes, and non-locomoting serum-deprived fibroblasts. These results suggest
      a gradient of actin assembly, highest in the cortex at the cytoplasm-membrane
      interface and lowest in the non-cortical perinuclear cytoplasm. We predicted that
      such a gradient would be maintained in part by phosphoinositide-regulated actin
      binding proteins because the intracellular free Ca2+ and pH are low and spatially
      constant in serum-deprived cells. The cytoplasm-membrane interface presents one
      surface where the assembly of actin is differentially regulated relative to the
      non-cortical cytoplasm. Several models, based on in vitro biochemistry, propose
      that phosphoinositide-regulated actin binding proteins are involved in local
      actin assembly. To test these models in living cells using imaging techniques, we
      prepared a new fluorescent analog of actin that bound profilin, a protein that
      interacts with phosphoinositides and actin-monomers in a mutually exclusive
      manner, with an order of magnitude greater affinity (Kd = 3.6 microM) than cys
      374-labeled actin (Kd > 30 microM), yet retained the ability to inhibit DNase I.
      Hence, we were able to directly compare the distribution and activity of a
      biochemical mutant of actin with an analog possessing closer to wild-type
      activity. Three-dimensional fluorescence microscopy of the fluorescent analog of
      actin with a high affinity for profilin revealed that it incorporated into
      cortical cytoplasmic fibers and was also distributed diffusely in the non
      cortical cytoplasm consistent with a bias of actin assembly near the surface of
      the cell. Fluorescence ratio imaging revealed that serum-deprived and migrating
      fibroblasts concentrated the new actin analog into fibers up to four-fold in the
      periphery and leading edge of these cells, respectively, relative to a soluble
      fluorescent dextran volume marker, consistent with the formation of a gradient of
      actin filament density relative to cell volume. Comparison of these gradients in
      the same living cell using analogs of actin with high and low affinities for
      profilin demonstrated that increased profilin binding enhanced the gradient.
      Profilin and related proteins may therefore function in part to bias the assembly
      of actin at the membrane-cytoplasm interface.

PMID- 8132721
TI  - PCP and me.

PMID- 8132722
TI  - Cholesterol levels in young adults: screen and intervene?
AB  - Early intervention is cost-effective over the long term: The cost of cholesterol
      lowering drugs is easily offset by savings in the treatment of cardiovascular
      disease. Besides, most interventions are dietary, not pharmacologic.

PMID- 8132723
TI  - The lost art of physical diagnosis.

PMID- 8132724
TI  - Refractory hypotension during warfarin therapy.

PMID- 8132725
TI  - Sudden collapse with new right bundle branch block.

PMID- 8132726
TI  - Immortality.

PMID- 8132727
TI  - Case in point. Rhinoscleroma.

PMID- 8132728
TI  - The consequences of renal artery stenosis.

PMID- 8132729
TI  - Breast cancer: 2. Recurrent disease.

PMID- 8132730
TI  - Osteonecrosis: pathogenesis and practicalities.

PMID- 8132731
TI  - Nephrogenic diabetes insipidus: causes revealed.
AB  - In congenital NDI, the failure of the renal tubules to respond to antidiuretic
      hormone is caused by mutation of the arginine vasopressin receptor gene. Two
      dozen different mutations have been identified to date--all with the same
      clinical consequences. Several causes of acquired NDI, of which lithium is the
      most common, are also discussed.

PMID- 8132733
TI  - Antimitochondrial (pyruvate dehydrogenase) antibodies in leprosy.
AB  - Sera from 69 patients with leprosy but without liver involvement were assayed for
      the presence of mitochondrial pyruvate dehydrogenase (PDH)-specific
      autoantibodies by enzyme-linked immunoabsorbent assay (ELISA), immunoblotting
      using PDH as an antigen and by enzymatic inhibition test. Twenty-seven of the
      leprosy serum samples (39.1%) were found to react with PDH by ELISA. However,
      unlike sera from primary biliary cirrhosis (PBC) patients, none of these were
      able to inhibit the PDH enzymatic activity. By immunoblotting, it was found that
      only 2 of the 27 positive sera recognized the 74-kD protein of the PDH complex,
      which is recognized by sera of most PBC patients. The antimitochondrial
      antibodies in lepra most probably recognize different epitopes than those in PBC.
      These findings may indicate that anti-PDH autoantibodies in patients with leprosy
      may arise by polyclonal B cell stimulation and may represent natural anti-PDH
      autoantibodies.

PMID- 8132732
TI  - Fc receptor-mediated signal transduction.
AB  - Receptors for the Fc domain of IgG (Fc gamma Rs) on leukocytes mediate a
      pleiotropic response following cross-linking by immune complexes. Signaling
      events following cross-linking of B and T cell antigen receptors, Fc epsilon RI,
      and Fc gamma Rs share common elements. In each, signaling is initiated by
      receptor cross-linking by antigen or immune complexes and results in the
      activation of src family kinases and ZAP-70-related tyrosine kinases, which
      associate with members of the receptor complex. Subsequent events include
      phosphorylation on tyrosine of multiple cellular substrates including
      phospholipase C gamma 1 and PI3-kinase. The [Ca2+]i flux is an event secondary to
      phospholipase C gamma 1 activation. Protein tyrosine kinase inhibitors block both
      early events such as [Ca2+]i flux and the later effects of cytokine release and
      cellular proliferation.

PMID- 8132734
TI  - Peripheral blood neutrophil production of interleukin-1 receptor antagonist and
      interleukin-1 beta.
AB  - The objective of this study was to characterize interleukin-1 receptor antagonist
      (IL-1ra) and interleukin-1 beta (IL-1 beta) production by human peripheral blood
      neutrophils (polymorphonuclear leukocytes; PMN). Unstimulated PMN contained IL
      1ra protein in the absence of IL-1ra mRNA; IL-1 beta mRNA and protein were
      undetectable. Lipopolysaccharide (LPS), granulocyte/macrophage colony-stimulating
      factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), individually,
      transiently increased IL-1ra steady-state mRNA levels in PMN, with associated
      increases in IL-1ra protein synthesis. LPS, GM-CSF, and TNF-alpha generated
      similar increases in IL-1 beta mRNA, yet only LPS resulted in detectable
      synthesis of IL-1 beta protein. IL-4 enhanced LPS-induced IL-1ra production by
      PMN and inhibited LPS-induced IL-1 beta production. by PMN and inhibited LPS
      induced IL-1 beta production. IL-1ra protein present within stimulated PMN
      supernatants existed in the 22- to 25-kD glycosylated form. Polymerase chain
      reaction amplification determined that only sIL-1ra mRNA was present within
      stimulated PMN; icIL-1ra mRNA was undetectable. These results indicate that
      freshly isolated PMN possess a small amount of IL-1ra protein and that these
      cells can respond to stimuli with a low level of sIL-1ra transcription and
      translation. PMN may be a major source of IL-1ra in inflammatory exudates where
      these cells predominate.

PMID- 8132735
TI  - Pentoxifylline suppresses interleukin-2-mediated activation of immature human
      natural killer cells by inhibiting endogenous tumor necrosis factor-alpha
      secretion.
AB  - We recently reported that immature human peripheral blood-derived natural killer
      (NK) cells, the free NK subset, can be activated by interleukin-2 (IL-2) to
      become killer cells and to undergo proliferation. Activation by IL-2 is dependent
      on endogenous secretion of tumor necrosis factor-alpha (TNF-alpha) by the free
      cells. Because pentoxifylline (PTX) inhibits TNF-alpha synthesis and secretion in
      monocytes, we hypothesized that PTX may also inhibit TNF-alpha secretion by NK
      cells and thus would inhibit IL-2-mediated activation of free cells. The free NK
      cells were separated from purified NK cells by flow cytometry and cell sorting of
      non-target binding cells. IL-2-mediated secretion of TNF-alpha by the free cells
      was inhibited by PTX. In the presence of PTX, IL-2-mediated activation of free
      cells into cytotoxic function, proliferation, and recruitment of binder and
      killer cells was markedly inhibited. Also, PTX inhibited IL-2-triggered
      upregulation of the expression of CD69, CD25, ICAM-1, and p75TNF-R on the cell
      surface. These findings demonstrate that PTX has a marked suppression on IL-2
      mediated activation of immature free NK cells and that the suppression is due, in
      large part, to PTX-mediated inhibition of endogenous TNF-alpha secretion. The
      implication of these findings in the clinical use of PTX for therapy is
      discussed.

PMID- 8132736
TI  - Suramin inhibits tumor cell cytotoxicity mediated through natural killer cells,
      lymphokine-activated killer cells, monocytes, and tumor necrosis factor.
AB  - Suramin, a polysulfonated naphthylurea, is an antitrypanosomal and antifilarial
      drug. Because of its anti-reverse transcriptase activity and antiproliferative
      activity, suramin is also used for the treatment of acquired immunodeficiency
      syndrome and cancer. In spite of these uses, very little is known about its
      effects on the immune system. In this report, we investigated the effects of
      suramin on peripheral blood mononuclear cells. We found that natural killer (NK)
      cell-mediated cytotoxicity against human erythroblastoid cell line K562 was
      completely inhibited by suramin in a dose-dependent manner. It also completely
      blocked lymphokine-activated killer (LAK) cell-mediated cytotoxicity against the
      human B lymphoblastoid cell lines Raji and Daudi. The cytotoxicity against the
      human melanoma tumor cell line A-375 mediated by unstimulated and stimulated
      monocytes was also suppressed by suramin. Maximum inhibition of monocyte-mediated
      cytotoxicity was observed when suramin was present during both the activation and
      the effector phases of cytotoxicity. Besides its effects on cell-mediated
      cytotoxicity, suramin also inhibited the cytotoxic effects of tumor necrosis
      factor (TNF) against different tumor cell lines. Furthermore, we found that
      suramin interferes with the binding of TNF with its receptor. Thus our results
      indicate that suramin overall downregulates the immune system by inhibiting cell
      mediated and TNF-mediated cytotoxicity against different tumor cells.

PMID- 8132737
TI  - 1,1'-Ethylidenebis(tryptophan) (Peak E) induces functional activation of human
      eosinophils and interleukin 5 production from T lymphocytes: association of
      eosinophilia-myalgia syndrome with a L-tryptophan contaminant.
AB  - This study was designed to clarify the important association between eosinophilia
      myalgia syndrome (EMS) and the L-tryptophan contaminant, "Peak E." To determine
      the functional activation of eosinophils induced by Peak E, eosinophil cationic
      protein (ECP) release was examined. Peak E augumented the release of ECP from
      peripheral blood normodense eosinophils by degranulation. Proliferative analysis
      using the human eosinophilic leukemia cell line EoL-3 showed prominent cellular
      replication in the presence of Peak E. Moreover, Peak E upregulated interleukin 5
      (IL-5) receptor levels on normodense eosinophils. Of particular interest, Peak E
      stimulated human splenic T cells produced bioactive and immunoreactive IL-5.
      Marked induction of IL-5 mRNA in Peak E-stimulated T cells was also shown by
      reverse-transcriptase polymerase chain reaction (RT-PCR). In contrast, L
      tryptophan without the contaminant showed none of these effects. Thus, these data
      suggest that Peak E might be involved in the pathogenesis of EMS through bimodal
      mechanism including IL-5 generation by T cells and potentiation of eosinophil
      functional activation.

PMID- 8132738
TI  - Differential induction of human monocyte transforming growth factor beta 1
      production and its regulation by interleukin 4.
AB  - We have previously shown that trauma patients' monocytes which are in vivo
      activated by multiple injury-induced mediators have elevated transforming growth
      factor-beta (TGF beta) bioactivity. Interleukin-4 (IL-4), a Th2 and B lymphocyte
      stimulatory factor, has been shown to inhibit monocyte production of a number of
      mediators both after lipopolysaccharide stimulation and after trauma-induced
      stimulation. However, IL-4 inhibitory effects appears to vary, depending on the
      mixture of inducing stimuli. Here we describe the in vitro IL-4 inhibition of
      human monocyte TGF beta bioactivity using several stimulation induction
      protocols: muramyl dipeptide stimulation alone, or after Fc gamma RI (CD64) cross
      linking induction, interferon-gamma (IFN gamma) priming, or trauma-generated in
      vivo mediator induction. IL-4 suppressed both muramyl dipeptide-induced TGF beta
      bioactivity and TGF beta mRNA in a dose-dependent fashion and was most effective
      when IL-4 was administered at initiation of normal monocyte stimulation. Muramyl
      dipeptide (MDP)-induced increases in trauma patients' monocyte TGF beta
      bioactivity were also inhibited by high doses of IL-4 (25 ng/ml). Fc gamma RI
      cross-linking increased MDP-induced normal monocyte TGF beta bioactivity, but
      this increase could be consistently inhibited only by very high IL-4
      concentrations (50 ng/ml). IL-4 did not consistently downregulate MDP-induced TGF
      beta bioactivity in IFN gamma-primed monocytes. IL-4 can suppress monocyte TGF
      beta production, as well as other monocyte mediators, but its efficiency depends
      on the stimuli combination present in the microenvironment.

PMID- 8132739
TI  - Anticardiolipin antibodies are elevated in drug-free, multiply affected families
      with schizophrenia.
AB  - The objective of this study was to measure anticardiolipin antibodies in patients
      and healthy relatives in multicase families with schizophrenia. Twenty-eight (28)
      multicase families with schizophrenia were examined. One hundred three drug-free
      patients and 66 first-degree relatives consented to evaluation by DSM-III-R
      criteria. Criteria for patient definition included the following: age > or = 16,
      a confirmed hospital diagnosis of schizophrenia, knowledge of biological parents,
      and consent to participate. Additional data were drawn from family history and
      medical records. Serum samples were tested separately for IgG and IgM
      anticardiolipin by enzyme-linked immunosorbent assay (ELISA) and designated
      positive/negative by comparison to the reactivity of an age-matched control
      group. IgG anticardiolipin antibodies were significantly more common in both
      patients and relatives compared to controls. IgM anticardiolipin antibodies were
      significantly more common in patients. In 75% of families at least one member was
      anticardiolipin positive and this positivity correlated with patient positivity.
      The relevance of anticardiolipin antibodies in both patients and healthy
      relatives of some multicase families to the pathogenesis of schizophrenia is
      discussed.

PMID- 8132740
TI  - A benign cultured colon adenoma bears three genetically altered colon cancer
      oncogenes, but progresses to tumorigenicity and transforming growth factor-beta
      independence without inactivating the p53 tumor suppressor gene.
AB  - We describe the spontaneous progression of a colon adenoma cell line to
      tumorigenicity and growth factor independence. This system allows direct
      comparison of biologic stages of malignant progression with alterations of colon
      cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line,
      is at early passages nontumorigenic in the nude mouse, unable to grow in soft
      agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO
      235 daughter passages 93 and higher have in culture spontaneously progressed to
      being weakly tumorigenic, but retain all other growth characteristics of VACO-235
      early passages. A mouse xenograft from late passage VACO-235 was reestablished in
      culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic,
      clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early
      passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles,
      expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO
      411 retains the identical genotype, still expressing only wild type p53. Colonic
      cells after ras mutation, APC mutation, and DCC inactivation remain
      nontumorigenic and growth factor dependent. Malignant progression involves at
      least two additional steps, and in VACO-411 can proceed by a novel pathway not
      requiring p53 inactivation.

PMID- 8132741
TI  - Calcium and protein kinetics in prepubertal boys. Positive effects of
      testosterone.
AB  - We investigated the effects of 4-6-wk administration of testosterone on calcium
      and protein metabolism in six healthy prepubertal short boys (mean age +/- SE =
      12.9 +/- 0.6 yr). At baseline, subjects received a 4-h infusion of L-[1
      13C]leucine and L-[2-15N]glutamine, and were given 42Ca intravenously, and 44Ca
      PO. Testosterone enanthate (approximately 3 mg/kg) was given I.M. 2 wk apart (two
      doses n = 5, three doses n = 1), and the study was repeated 4-5 d after the last
      injection. After testosterone therapy, there were significant increases in serum
      testosterone and mean peak and total growth hormone concentrations. Net calcium
      absorption (Va) and retention (Vbal) also increased (Va 13.3 +/- 2.3 vs 21.5 +/-
      2.3; mg.kg-1.d-1, Vbal 8.0 +/- 2.1 vs 16.6 +/- 2.5, mg.kg-1.d-1, P < .05 both),
      as well as Ca's net forward flow into bone and total exchangeable pool (16 and
      20%, respectively). The rate of appearance of leucine (an indicator of
      proteolysis) increased by 17.6 +/- 5.9%, P = 0.036. Leucine oxidation decreased
      by 48.6 +/- 8.0%, P = 0.004; thus, nonoxidative leucine disappearance, which
      estimates protein synthesis, increased significantly by 34.4 +/- 7.7%, P = 0.009.
      Glutamine's rate of appearance also increased (+32%), mostly through enhanced
      glutamine de novo synthesis (+42%). In conclusion, short term testosterone
      administration significantly increases calcium's retention and net forward flow
      into bone in prepubertal humans, as well as whole body estimates of protein and
      calcium anabolism. These effects may represent a pure androgen effect, an
      amplification of growth hormone's action or some combination of these factors.

PMID- 8132742
TI  - Leukotriene A4 hydrolase in human bronchoalveolar lavage fluid.
AB  - We examined cell-free human bronchoalveolar lavage fluid (BALF) for enzymes of
      the 5-lipoxygenase pathway. BALF was obtained from six patients who were active
      smokers and six nonsmokers. Enzymatic activity in cell-free BALF was assessed by
      specific assays for leukotriene (LT) A4 hydrolase, 5-lipoxygenase, and LTC4
      synthase using HPLC. Only LTA4 hydrolase enzymatic activity was found. This
      activity ranged from 101 to 667 when expressed as picomoles of LTB4 produced per
      milliliter BALF. Enzymatic activity in smokers vs nonsmokers was 484 +/- 120 vs
      129 +/- 32 pmol LTB4/ml BALF (mean +/- SD, P < 0.0001). There were no
      leukotrienes found in BALF before assay. Immunoblot analysis revealed an
      immunoreactive band at a relative molecular mass of 69,000 D in all samples,
      consistent with LTA4 hydrolase, but no evidence of 5-lipoxygenase. BALF had
      greater LTA4 hydrolase activity per milligram of protein than neutrophil cytosol,
      epithelial cell cytosol, plasma, or serum. The synthesis of LTB4 was
      significantly increased when neutrophils were stimulated in BALF. These data
      indicate the selective presence of LTA4 hydrolase in BALF which is significantly
      increased in smokers. This enzyme in BALF may contribute to the inflammatory
      response in tobacco-related lung disease.

PMID- 8132743
TI  - High density lipoproteins stimulate the production and secretion of endothelin-1
      from cultured bovine aortic endothelial cells.
AB  - The concentration of HDL in the blood inversely correlates with the incidence of
      cardiovascular disease, probably related to the ability of these lipoproteins to
      efflux cholesterol from vascular cells. it is also possible that HDL affect the
      production or action of vasoactive peptides implicated in the development of
      vascular diseases. Therefore, we determined the effects of human HDL on the
      production and secretion of endothelin-1 (ET-1) from cultured bovine aortic
      endothelial cells. HDL produced a highly significant stimulation of endothelin
      secretion (maximum 240% of control), even at very low levels of lipoproteins (1
      microgram/ml). HDL also stimulated the translation of ET-1 by twofold in the
      bovine aortic endothelial cells. In contrast, HDL had no significant effect on
      steady state mRNA levels, transcript degradation, or transcription. Stimulation
      of ET-1 secretion by HDL was dependent on protein kinase C activation. Purified
      apo A-I, the major apoprotein of HDL, increased ET-1 secretion and translation
      approximately 85% as potently as HDL. Our results indicate that low
      concentrations of human HDL strongly stimulate the production of ET-1, a powerful
      vasoconstrictor and mitogen for the vascular smooth muscle cell. We propose that
      HDL may participate in the regulation of vasomotor tone through this potentially
      important effect in the vasculature.

PMID- 8132744
TI  - Neutrophil migration inhibitory properties of polyunsaturated fatty acids. The
      role of fatty acid structure, metabolism, and possible second messenger systems.
AB  - The n-3 polyunsaturated fatty acids (PUFA) appear to have antiinflammatory
      properties that can be partly explained by their biological activity on
      leukocytes. Since leukocyte emigration is an essential component of the
      inflammatory response, we have examined the effects of the n-3 PUFA
      (eicosapentaenoic and docosahexaenoic acids) on neutrophil random and chemotactic
      movement. Preexposure of neutrophils for 15-30 min to 1-10 micrograms/ml PUFA
      reduced the random and chemotactic migration to both FMLP- and fungi-activated
      complement. The inhibitory effect diminished with increasing saturation and
      carbon chain length, and methylation abolished this activity. Arachidonic and
      docosahexaenoic acids were the most active fatty acids. The PUFA concentration
      required to inhibit migration was dependent on cell number, suggesting that the
      fatty acid effects on leukocyte migration in vivo may be governed by the stage of
      the inflammatory response. It was concluded that the PUFA rather than their
      metabolites were responsible for the inhibition since: (a) antioxidants did not
      prevent the PUFA-induced migration inhibition and the hydroxylated intermediates
      were less active, and (b) inhibitors of the cyclooxygenase and lipoxygenase
      pathways were without effect. Inhibitors of protein kinases and calmodulin
      dependent enzyme system did not prevent the PUFA-induced migration inhibition,
      which was also independent of phospholipase D-catalyzed hydrolysis of
      phospholipids. It is also shown that PUFA decrease the FMLP-induced Ca2+
      mobilization.

PMID- 8132745
TI  - Supravalvular aortic stenosis associated with a deletion disrupting the elastin
      gene.
AB  - Supravalvular aortic stenosis (SVAS) is an inherited vascular disease that can
      cause heart failure and death. SVAS can be inherited as an autosomal dominant
      trait or as part of a developmental disorder, Williams syndrome (WS). In recent
      studies we presented evidence suggesting that a translocation disrupting the
      elastin gene caused SVAS in one family while deletions involving the entire
      elastin locus caused WS. In this study, pulsed-field, PCR, and Southern analyses
      showed that a 100-kb deletion of the 3' end of the elastin gene cosegregated with
      the disease in another SVAS family. DNA sequence analysis localized the
      breakpoint between elastin exons 27 and 28, the same region disrupted by the SVAS
      associated translocation. These data indicate that mutations in the elastin gene
      cause SVAS and suggest that elastin exons 28-36 may encode critical domains for
      vascular development.

PMID- 8132746
TI  - Differential effects of insulin-like growth factor I and growth hormone on
      developmental stages of rat growth plate chondrocytes in vivo.
AB  - Skeletal growth depends upon enchondral ossification in growth plate cartilage,
      within which chondrocytes undergo well defined stages of maturation. We infused
      IGF-I or growth hormone (GH), two key regulators of skeletal growth, into
      hypophysectomized rats and compared their effects on growth plate chondrocyte
      differentiation using qualitative and quantitative autoradiography, stereology,
      and incident light fluorescence microscopy. Stem cell cycle time was shortened
      from 50 to 15 and 8 d after treatment with IGF-I and GH, respectively.
      Proliferating cell cycle time decreased from 11 to 4.5 and 3 d, and duration of
      the hypertrophic phase decreased from 6 to 4 and 2.8 d. Average matrix volume per
      cell at each differentiation stage was similar for normal, hormone-treated, and
      untreated hypophysectomized groups. Mean cell volume and cell height were
      significantly reduced by hypophysectomy at the proliferative and hypertrophic
      stages, but were restored to physiological values by IGF-I and GH. In contrast,
      cell productivity, i.e., increases in cell volume, height, and matrix production
      per unit of time, did not reach normal values with either IGF-I or GH, and this
      parameter was inversely proportional to cell cycle time or phase duration. IGF-I
      and GH are thus capable of stimulating growth plate chondrocytes at all stages of
      differentiation, albeit to variable degrees with respect to individual cell
      activities. Although it is generally accepted that GH acts at both the stem and
      proliferating phases of chondrocyte differentiation, our data represent the first
      evidence in vivo that IGF-I is also capable of stimulating stem cells.

PMID- 8132747
TI  - Myocardial protection after whole body heat stress in the rabbit is dependent on
      metabolic substrate and is related to the amount of the inducible 70-kD heat
      stress protein.
AB  - The aims of this study were to examine the effects of whole body heat stress and
      subsequent stress protein induction on glycolytic metabolism, mitochondrial
      metabolism, and calcium handling within the heart. The effect of heat stress on
      glycolytic and mitochondrial pathways was examined by measuring contractile
      performance in the presence of glucose and pyruvate, respectively. Calcium
      handling was assessed using force-interval relationships. Right ventricular
      papillary muscles taken from heat-stressed and control rabbit hearts were
      superfused with Kreb's solution containing either glucose or pyruvate and
      rendered hypoxic for 30 min. After reoxygenation, the greatest recovery of
      contractile function occurred in the heat-stressed muscles with pyruvate as
      substrate; there was, however, no difference in the force-interval relationship
      between the groups. The degree of contractile recovery was related to the content
      of the inducible 70-kD but not the 65-kD, heat stress protein. This study
      suggests that heat stress enhances the ability of rabbit papillary muscle to use
      pyruvate, but not glucose, after reoxygenation, and that the differences seen in
      contractility may be secondary to induction of the 72-kD stress protein.

PMID- 8132748
TI  - Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues. Effects of
      interleukin-1 beta, phorbol ester, and corticosteroids.
AB  - High levels of immunoreactive cyclooxygenase (Cox; prostaglandin H synthase) are
      present in synovia from patients with rheumatoid arthritis (RA). We now show that
      the recently identified inducible isoform of Cox, Cox-2, is expressed in synovia
      from patients with RA. To further explore modulation of the Cox isoforms in RA
      synovial tissues, we examined the expression and modulation of Cox-1 and -2 in
      rheumatoid synovial explant cultures and cultured rheumatoid synovial fibroblast
      like cells (synoviocytes). Immunoprecipitation of in vitro labeled proteins and
      Western blot analysis demonstrated the presence of both Cox-1 and -2 under basal
      conditions in freshly explanted rheumatoid synovial tissues. De novo synthesis of
      Cox-2 polypeptide was enhanced by IL-1 beta or PMA, and dramatically suppressed
      by dexamethasone (dex). Cox-1 expression, under the same conditions, showed only
      minor variation. Since mRNA for Cox-2 is highly unstable, we examined the
      regulation of Cox-2 transcripts in cultured rheumatoid synoviocytes. Under basal
      conditions both Cox-1 and -2 mRNAs were present at low levels, but Cox-2 mRNA was
      markedly increased by treatment with IL-1 beta or PMA. dex markedly suppressed
      the induction of Cox-2 mRNA. In sharp contrast, Cox-1 transcripts were not
      modulated by IL-1 beta or dex. These data suggest that modulation of Cox-2
      expression by IL-1 beta and corticosteroids may be an important component of the
      inflammatory process in synovial tissues from patients with RA.

PMID- 8132749
TI  - Defective respiratory capacity and mitochondrial protein synthesis in
      transformant cybrids harboring the tRNA(Leu(UUR)) mutation associated with
      maternally inherited myopathy and cardiomyopathy.
AB  - We studied the physiometabolic effects of a mitochondrial DNA (mtDNA)
      heteroplasmic point mutation, the A-->G3260 transition associated with maternally
      inherited myopathy and cardiomyopathy. To eliminate the possible influence of the
      autochthonous nuclear gene set, we fused myoblast-derived cytoplasts of a patient
      with a human tumoral cell line deprived of mtDNA (Rho degrees). The presence and
      amount of the mutant G3260 vs the wild-type A3260 were measured by solid phase
      minisequencing. We observed a marked reduction of the percentage of mutant mtDNA
      in the culture system compared with that measured in the donor's muscle biopsy,
      suggesting the presence of negative selection against the mutation. Furthermore,
      stable mitotic segregation of the two mtDNA populations was observed in 18 of 19
      transformant clones, suggesting the presence of intraorganelle and possibly
      intracellular homoplasmy in the precursor cells of the donor. Several indexes of
      mtDNA-related respiratory capacity, including oxygen consumption, complex I- and
      complex IV-specific activities, and lactate production, were markedly abnormal in
      the clones containing a high proportion of mutant mtDNA, as compared with those
      containing homoplasmic wild-type mtDNA, possibly because of impaired
      mitochondrial protein synthesis. We conclude that (a) the A-->G3260 transition is
      indeed responsible for the mitochondrial disorder identified in the donor
      patient, and (b) transformant cybrid system gives direct evidence of the
      mitochondrial origin of a genetic disorder and should be adopted for the
      evaluation of the pathogenic potential of the mtDNA mutations.

PMID- 8132750
TI  - Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.
      Effects of mutant gene dosage on phenotype.
AB  - Neonatal severe hyperparathyroidism is a rare life-threatening disorder
      characterized by very high serum calcium concentrations (> 15 mg/dl). Many cases
      have occurred in families with familial hypocalciuric hypercalcemia, a benign
      condition transmitted as a dominant trait. Among several hypothesized
      relationships between the two syndromes is the suggestion that neonatal severe
      hyperparathyroidism is the homozygous form of familial hypocalciuric
      hypercalcemia. To test this hypothesis, we refined the map location of the gene
      responsible for familial hypocalciuric hypercalcemia on chromosome 3q. Analyses
      in 11 families defined marker loci closely linked to the gene responsible for
      familial hypocalciuric hypercalcemia. These loci were then analyzed in four
      families with parental consanguinity and offspring with neonatal severe
      hyperparathyroidism. Each individual who was homozygous for loci that are closely
      linked to the gene responsible for familial hypocalciuric hypercalcemia had
      neonatal severe hyperparathyroidism. The calculated odds of linkage between these
      disorders of > 350,000:1 (lod score = 5.56). We conclude that dosage of the gene
      defect accounts for these widely disparate clinical phenotypes; a single
      defective allele causes familial hypocalciuric hypercalcemia, while two defective
      alleles causes neonatal severe hyperparathyroidism.

PMID- 8132751
TI  - Characterization of mixed syngeneic-allogeneic and syngeneic-xenogeneic islet
      graft rejections in mice. Evidence of functional impairment of the remaining
      syngeneic islets in xenograft rejections.
AB  - Allogeneic mouse islets or xenogeneic rat islets, or fetal porcine islets were
      implanted under the renal capsule of C57BL/6 mice either alone or carefully mixed
      with syngeneic islets. With this experimental model the syngeneic islets,
      although not rejected themselves, are exposed to cytokines and inflammatory
      mediators released during either allograft or xenograft rejection. No differences
      in insulin content could be observed between mixed islet grafts and pure
      syngeneic islet grafts 6 wk after transplantation. Neither was there any
      morphological evidence of a non-specific destruction of syngeneic islets. These
      findings suggest that the mechanisms of both allograft and xenograft rejections
      are highly specific. The hormone release from the mixed syngeneic-allogeneic
      grafts was similar to that from pure syngeneic islet grafts. In contrast, a
      pronounced impairment of both the first and second phases of insulin release was
      observed 2 wk after implantation in mixed syngeneic-xenogeneic islet grafts. When
      perfusing the mixed islet graft after completed rejection of the concordant
      xenogeneic rat islets (6 wk after implantation), the insulin release from the
      remaining syngeneic mouse islets was identical to that of control grafts.
      However, syngeneic mouse islets exposed to the rejection mechanism of the
      discordant xenogenic pig islet-like cell clusters did not attain a complete
      functional recovery.

PMID- 8132752
TI  - Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase
      mutations.
AB  - Pancreatic beta-cell function was studied in six subjects with mutations in the
      enzyme glucokinase (GCK) who were found to have elevated fasting and postprandial
      glucose levels in comparison to six normoglycemic controls. Insulin secretion
      rates (ISRs) were estimated by deconvolution of peripheral C-peptide values using
      a two-compartment model and individual C-peptide kinetics obtained after bolus
      intravenous injections of biosynthetic human C-peptide. First-phase insulin
      secretory responses to intravenous glucose and insulin secretion rates over a 24
      h period on a weight maintenance diet were not different in subjects with GCK
      mutations and controls. However, the dose-response curve relating glucose and ISR
      obtained during graded intravenous glucose infusions was shifted to the right in
      the subjects with GCK mutations and average ISRs over a glucose range between 5
      and 9 mM were 61% lower than those in controls. In the controls, the beta cell
      was most sensitive to an increase in glucose at concentrations between 5.5 and
      6.0 mM, whereas in the patients with GCK mutations the point of maximal
      responsiveness was increased to between 6.5 and 7.5 mM. Even mutations that
      resulted in mild impairment of in vitro enzyme activity were associated with a >
      50% reduction in ISR. The responsiveness of the beta cell to glucose was
      increased by 45% in the subjects with mutations after a 42-h intravenous glucose
      infusion at a rate of 4-6 mg/kg per min. During oscillatory glucose infusion with
      a period of 144 min, profiles from the subjects with mutations revealed reduced
      spectral power at 144 min for glucose and ISR compared with controls, indicating
      decreased ability to entrain the beta cell with exogenous glucose. In conclusion,
      subjects with mutations in GCK demonstrate decreased responsiveness of the beta
      cell to glucose manifest by a shift in the glucose ISR dose-response curve to the
      right and reduced ability to entrain the ultradian oscillations of insulin
      secretion with exogenous glucose. These results support a key role for the enzyme
      GCK in determining the in vivo glucose/ISR dose-response relationships and define
      the alterations in beta-cell responsiveness that occur in subjects with GCK
      mutations.

PMID- 8132753
TI  - Comparison of the metabolic effects of recombinant human insulin-like growth
      factor-I and insulin. Dose-response relationships in healthy young and middle
      aged adults.
AB  - The actions of recombinant human insulin-like growth factor-I (rhIGF-I) and
      insulin were compared in 21 healthy young (24 +/- 1 yr) and 14 healthy middle
      aged (48 +/- 2 yr) subjects during 3-h paired euglycemic clamp studies using one
      of three doses (rhIGF-I 0.2, 0.4, and 0.8 micrograms/kg.min and insulin 0.2, 0.4,
      and 0.8 mU/kg.min, doses chosen to produce equivalent increases in glucose
      uptake). In younger subjects, rhIGF-I infusions suppressed insulin by 19-33%, C
      peptide by 47-59% and glucagon by 33-47% (all, P < 0.02). The suppression of C
      peptide was less pronounced with insulin than with rhIGF-I (P < 0.007). The
      metabolic responses to rhIGF-I and insulin were remarkably similar: not only did
      both hormones increase glucose uptake and oxidation in a nearly identical
      fashion, but they also produced similar suppression of glucose production, free
      fatty acid levels, and fat oxidation rates. In contrast, rhIGF-I had a more
      pronounced amino acid-lowering effect than did insulin (P < 0.004). In middle
      aged subjects, basal IGF-I levels were 44% lower (P < 0.0001) whereas basal
      insulin and C-peptide were 20-25% higher than in younger subjects. Age did not
      alter the response to rhIGF-I. However, insulin-induced stimulation of glucose
      uptake was blunted in older subjects (P = 0.05). Our data suggest that absolute
      IGF-I and relative insulin deficiency contribute to adverse metabolic changes
      seen in middle age.

PMID- 8132754
TI  - Alterations of human placental epidermal growth factor receptor in intrauterine
      growth retardation.
AB  - We studied human placental microvillous EGF receptor (EGFR) and its relationship
      with maternal and placental features in 14 cases of intrauterine growth
      retardation. Placental EGFR phosphorylation was significantly decreased or absent
      in 12 cases of small for gestational age neonates, as shown by SDS-PAGE,
      autoradiography, and scanning analysis. Specific [125I]EGF binding and Scatchard
      plots of the binding data showed a decreased number of EGFR in 6 of the 12 cases,
      with a mean maximal binding capacity of 1.09 +/- 0.32 pmol/mg for high affinity
      sites (mean control value = 2.30 +/- 0.23 pmol/mg). Most of the hypertensive
      women and smokers belonged to this subgroup. In three of the remaining six cases
      of small gestational age placentas with low EGFR phosphorylation, there was no
      maternal pathology or significant parenchymatous placental lesions. Five showed a
      175-kD EGFR species when probed by [125I]EGF cross-linking and Western blotting
      with RK2 and C-Term, two polyclonal anti-EGFR antibodies, suggesting abnormal
      transduction of the EGF-induced signal. The sixth placenta yielded a single 145
      kD EGFR band consistent with an abnormal EGFR structure; Western blot analysis
      showed no immunoreactive band. In conclusion, maternal and placental pathologies
      in intrauterine growth retardation are associated with various alterations of
      placental EGFR, pointing out the importance of EGFR ligands in the regulatory
      pathway of placental and fetal growth.

PMID- 8132755
TI  - Skeletal muscle protein tyrosine phosphatase activity and tyrosine phosphatase 1B
      protein content are associated with insulin action and resistance.
AB  - Particulate and cytosolic protein tyrosine phosphatase (PTPase) activity was
      measured in skeletal muscle from 15 insulin-sensitive subjects and 5 insulin
      resistant nondiabetic subjects, as well as 18 subjects with non-insulin-dependent
      diabetes mellitus (NIDDM). Approximately 90% of total PTPase activity resided in
      the particulate fraction. In comparison with lean nondiabetic subjects,
      particulate PTPase activity was reduced 21% (P < 0.05) and 22% (P < 0.005) in
      obese nondiabetic and NIDDM subjects, respectively. PTPase1B protein levels were
      likewise decreased by 38% in NIDDM subjects (P < 0.05). During hyperinsulinemic
      glucose clamps, glucose disposal rates (GDR) increased approximately sixfold in
      lean control and twofold in NIDDM subjects, while particulate PTPase activity did
      not change. However, a strong positive correlation (r = 0.64, P < 0.001) existed
      between particulate PTPase activity and insulin-stimulated GDR. In five obese
      NIDDM subjects, weight loss of approximately 10% body wt resulted in a
      significant and corresponding increase in both particulate PTPase activity and
      insulin-stimulated GDR. These findings indicate that skeletal muscle particulate
      PTPase activity and PTPase1B protein content reflect in vivo insulin sensitivity
      and are reduced in insulin resistant states. We conclude that skeletal muscle
      PTPase activity is involved in the chronic, but not acute regulation of insulin
      action, and that the decreased enzyme activity may have a role in the insulin
      resistance of obesity and NIDDM.

PMID- 8132756
TI  - Metabolic clearance of recombinant human growth hormone in health and chronic
      renal failure.
AB  - Despite the increasing therapeutic use of recombinant human growth hormone
      (rhGH), its metabolic clearance has not been investigated in detail. To evaluate
      the kinetics of rhGH as a possible function of GH plasma concentration and
      glomerular filtration rate (GFR), we investigated the steady state metabolic
      clearance rate (MCR), disappearance half-life, and apparent volume of
      distribution of rhGH at low and high physiological as well as supraphysiological
      plasma GH levels during pharmacological suppression of endogenous GH secretion in
      human subjects with normal and reduced renal function. GH in plasma and urine was
      determined by an immunoradiometric assay, and GFR by inulin clearance. In all
      subjects MCR decreased and plasma half-life increased with increasing plasma GH
      concentrations (P < 0.001). MCR of rhGH was approximately half in patients with
      chronic renal failure at each GH level and plasma half-life was increased by 25
      50%. Allowing for the linear dependence of MCR on GFR and assuming single
      compartment distribution, the estimated renal fraction of total MCR was 25-53 and
      4-15% in controls and patients, respectively. Saturation of extrarenal disposal
      of GH was suggested by an inverse hyperbolic relationship between extrarenal MCR
      and plasma GH concentrations in all subjects. Fractional GH excretion was up to
      1,000-fold higher in patients than in controls. We conclude that MCR of hGH is a
      function of plasma GH concentrations and GFR. Extrarenal elimination is saturable
      in the upper physiological range of GH concentrations, whereas renal MCR is
      independent of plasma GH levels. The kidney handles GH like a microprotein
      involving glomerular filtration, tubular reabsorption, and urinary excretion.

PMID- 8132757
TI  - Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia
      in a rat model.
AB  - Intimal hyperplasia is induced by therapeutic vascular interventions and often
      results in clinically important narrowing of the vascular lumen. Examination of
      the role of TGF-beta 1 in a rat carotid artery injury model confirmed the
      presence of a previously reported increase in TGF-beta 1 mRNA in the media of
      injured arteries. Administration of neutralizing anti- TGF-beta 1 antibodies
      significantly (P < 0.05) reduced the size of the intimal lesions that developed
      after carotid balloon injury. A control antibody had no effect. The
      intimal/medial area ratio was also reduced in the anti-TGF-beta 1 group relative
      to controls (P < 0.01). Immunohistochemical staining showed that two TGF-beta 1
      induced extracellular matrix components, EDA + fibronectin and versican, were
      greatly increased in the untreated neointimal lesions, but were almost completely
      absent from the lesions of the anti-TGF-beta 1-treated animals. We conclude that
      TGF-beta 1 is causally involved in the development of intimal hyperplasia, and
      that anti-TGF-beta 1 agents may be useful in achieving at least partial control
      of this condition.

PMID- 8132758
TI  - Cocaine differentially inhibits neuronal differentiation and proliferation in
      vitro.
AB  - The outcome of in utero cocaine exposure is unclear. To determine if cocaine
      affects neuronal growth and differentiation, we used PC-12 cells, which have a
      mitogenic response to IGF-I and differentiate into neurons on exposure to nerve
      growth factor. Differentiation was quantified as neurite extension after a 72-h
      exposure to 20 ng/ml nerve growth factor (dosage at 50% maximal effectiveness)
      and cocaine doses ranging from 0.01 to 10 micrograms/ml. The results were 49 +/-
      2, 40 +/- 3, 29 +/- 2, 23 +/- 2, and 12 +/- 2% differentiation with respective
      cocaine concentrations of 0, 0.01, 0.1, 1, and 10 micrograms/ml (P < 0.0001).
      Cocaine stability studies showed insignificant spontaneous hydrolysis under the
      conditions of this study. Cocaine did not affect cell viability or number, but
      had a relatively modest, statistically significant (P < 0.001) inhibitory effect
      on IGF-I-stimulated thymidine incorporation. The dose-response curves for
      differentiation vs mitogenic response differed significantly (P = 0.021).
      Therefore, cocaine inhibition of these processes is probably mediated by
      different mechanisms, and not caused by generalized toxicity. To our knowledge,
      this is the first demonstration of cocaine effects on neuronal multiplication and
      differentiation in vitro. The results suggest in utero exposure may directly
      impair brain development.

PMID- 8132759
TI  - Effects of dietary cholesterol on cholesterol and bile acid homeostasis in
      patients with cholesterol gallstones.
AB  - We examined changes in cholesterol and bile acid metabolism produced by dietary
      cholesterol in gallstone subjects and matched controls. Healthy women were
      recruited and, after confirming the presence or absence of radiolucent
      gallstones, they were studied on regular diets and again on the same diet
      supplemented with five eggs daily for 15-18 d. Studies included plasma lipids,
      lipoproteins and apolipoproteins, dietary records, cholesterol absorption,
      cholesterol synthesis, plasma clearance of chylomicron remnants, biliary lipid
      composition, and secretion and bile acid kinetics. On low cholesterol, gallstone
      subjects absorbed a slightly lower fraction of dietary cholesterol, synthesized
      more cholesterol, and had smaller bile acid pools and faster fractional turnover
      rate (FTR) of bile acids. On high cholesterol, the fraction of cholesterol
      absorbed decreased in both groups and cholesterol synthesis decreased, especially
      in the gallstone group. Biliary cholesterol secretion increased in the gallstone
      group only. FTR of bile acids did not change in either group. Bile acid synthesis
      and pool tended to increase (P = NS) in the controls, but in gallstone subjects,
      synthesis and pool size decreased. We concluded that in gallstone subjects
      cholesterol and bile acid homeostasis is significantly altered, and that
      increasing dietary cholesterol increases biliary cholesterol secretion and
      decreases bile acid synthesis and pool, changes associated with cholesterol
      gallstone formation.

PMID- 8132760
TI  - Deletions in the COL4A5 collagen gene in X-linked Alport syndrome.
      Characterization of the pathological transcripts in nonrenal cells and
      correlation with disease expression.
AB  - The type IV collagen alpha 5 chain (COL4A5) gene of 88 unrelated male patients
      with X-linked Alport syndrome was tested for major gene rearrangements by
      Southern blot analysis, using COL4A5 cDNA probes. 14 different deletions were
      detected, providing a 16% deletion rate in the COL4A5 gene in the patient
      population. The deletions are dispersed all over the gene with different sizes,
      ranging from 1 kb to the complete absence of the gene (> 250 kb) in one patient.
      In four patients with intragenic deletions, absence of the alpha 3 (IV) chain in
      the glomerular basement membrane was demonstrated by immunohistochemical studies.
      This finding supports the hypothesis that abnormalities in the alpha 5 (IV) chain
      may prevent normal incorporation of the alpha 3 (IV) chain into the glomerular
      basement membrane. Direct sequencing of cDNA amplified from lymphoblast mRNA of
      four patients with internal gene deletions, using appropriate combinations of
      primers amplifying across the predicted boundaries of the deletions, allowed us
      to determine the effect of the genomic rearrangements on the transcripts and, by
      inference, on the alpha 5 (IV) chain. Regardless of the extent of deletion and of
      the putative protein product, the 14 deletions occur in patients with juvenile
      type Alport syndrome.

PMID- 8132761
TI  - Mechanism of the diastolic dysfunction induced by glycolytic inhibition. Does
      adenosine triphosphate derived from glycolysis play a favored role in cellular
      Ca2+ homeostasis in ferret myocardium?
AB  - Several lines of evidence indicate that glycolysis is especially important for
      normal diastolic relaxation and for the maintenance of cellular ion homeostasis
      in myocardium. To elucidate whether the glycolytic flux of ATP contributes to
      diastolic tone and to the regulation of intracellular Ca2+, myocardial content of
      sugar phosphates ([SP]) and intracellular Ca2+ concentration ([Ca2+]i) were
      measured in isolated, perfused ferret hearts using nuclear magnetic resonance.
      Glucose and acetate were used as substrates for glycolysis and oxidative
      phosphorylation, respectively. Glycogen was effectively depleted after 15-min
      perfusion with glucagon (2 mg/liter), as verified by the lack of rise in [SP]
      during exposure to iodoacetate (100 microM) in substrate-free perfusate. Despite
      the fact that glycolytic flux had been blocked both by iodoacetate and by absence
      of substrate, end-diastolic left ventricular pressure (EDP) remained unchanged (P
      > 0.15, n = 6). The subsequent addition of glucose to the perfusate led to SP
      accumulation and a marked rise in EDP, with a significant correlation between EDP
      and [SP] (r = 0.86 +/- 0.04, P < 0.01, n = 6). A similar correlation was observed
      when glucose in the perfusate was replaced by 2-deoxyglucose (r = 0.78 +/- 0.09,
      P < 0.01, n = 3). Fluorine nuclear magnetic resonance measurements of [Ca2+]i
      verified that EDP faithfully reports changes in diastolic [Ca2+]i under the
      present experimental conditions. Thus, intracellular Ca2+ overload is caused by
      the accumulation of SP rather than by the inhibition of glycolysis per se.
      Glycolysis may appear to be important because its by-products are deleterious,
      and not necessarily because glycolytically derived ATP plays a favored role in
      ion homeostasis.

PMID- 8132762
TI  - Interleukin 1 alpha causes rapid activation of cytosolic phospholipase A2 by
      phosphorylation in rat mesangial cells.
AB  - We have shown previously that interleukin 1 (IL-1) stimulates eicosanoid
      production in glomerular mesangial cells (MC) by de novo synthesis of a 14-kD,
      group II phospholipase A2 (PLA2). IL-1-stimulated prostaglandin E2 synthesis
      precedes expression of this enzyme, suggesting that another PLA2 isoform must be
      more rapidly activated. In the presence but not absence of calcium inophore,
      [3H]arachidonate release is increased significantly as early as 5 min after
      addition of IL-1, and IL-1 concurrently stimulates a Ca(2+)-dependent
      phospholipase activity, which was characterized as the cytosolic form of PLA2
      (cPLA2). IL-1 does not alter either cPLA2 mRNA expression or mass in serum
      stimulated MC, suggesting that cPLA2 activity is increased by a posttranslational
      modification. IL-1 treatment for 30 min doubles 32P incorporation into
      immunoprecipitable cPLA2 protein, concordant with the increase in enzyme
      activity. Immunoblot analysis of extracts derived from IL-1-treated (30 min)
      cells demonstrates a decreased mobility of cPLA2, and treatment of MC lysates
      with acid phosphatase significantly reduces cytokine-activated cPLA2 activity,
      further indicating that IL-1 stimulates phosphorylation of the enzyme. IL-1
      treatment (24 h) of serum-deprived MC doubled cPLA2 mRNA, protein, and activity.
      In summary, IL-1 increases cPLA2 activity in a biphasic, time-dependent manner
      both by posttranslational modification and de novo synthesis. We consider cPLA2
      activation a key step in IL-1-stimulated synthesis of pro-inflammatory, lipid
      mediators, and an integral event in the phenotypic responses induced in target
      cells by this cytokine.

PMID- 8132763
TI  - Persistence of the fetal pattern of tropoelastin gene expression in severe
      neonatal bovine pulmonary hypertension.
AB  - Neonatal hypoxic pulmonary hypertension causes increases and spatial changes in
      tropoelastin expression in pulmonary arteries. However, it is not clear if this
      is due to recruitment of quiescent smooth muscle cells (SMC) into an elastin
      producing phenotype or persistence of the fetal pattern of tropoelastin gene
      expression. We evaluated the distribution and relative concentration of
      tropoelastin mRNA in intralobar pulmonary arteries from late gestation fetuses
      and in animals exposed to hypobaric hypoxia (430 mmHg) from birth for 1, 3, 7, or
      14 d, as well as in age-matched and adult room air-breathing controls. In situ
      hybridization demonstrated that tropoelastin mRNA was distributed throughout the
      entire radius of the pulmonary vessel wall in the fetus and newborn calf. By 15 d
      of age, only cells in the inner third of the media expressed tropoelastin mRNA,
      and by adulthood no tropoelastin mRNA was detected in the vessel wall. These
      findings demonstrated that tropoelastin expression shuts off in a spatially
      specific pattern, moving from the abluminal to the luminal side of the medial in
      the neonatal pulmonary artery when pressures and resistance are falling. In the
      aorta of 15-d-old calves, tropoelastin mRNA expression was seen equally
      throughout the media, indicating tissue-specific regulation of elastin in the
      neonatal period. In contrast, intralobar pulmonary arteries from calves exposed
      to hypoxia, which prevented the normal postnatal decline in pulmonary artery
      pressure, maintained the fetal pattern and levels of tropoelastin mRNA expression
      at all time points. Thus, rather than causing a recruitment of SMC into an
      elastin-producing phenotype, neonatal pulmonary hypertension caused a persistence
      of the fetal pattern of tropoelastin expression in medial SMC. Cell-free
      translation showed that the same tropoelastin isoforms were made by mRNA from
      control and hypertensive calves and, unlike the ligamentum nuchae, did not change
      during the transition from fetal to neonatal life. We conclude that pulmonary
      hypertension in the neonate perturbs the normal postpartum repression of
      tropoelastin expression resulting in a persistence of the fetal spacial and
      isoform patterns of tropoelastin gene expression.

PMID- 8132764
TI  - Local delivery of dexamethasone for prevention of neointimal proliferation in a
      rat model of balloon angioplasty.
AB  - A periadventitial polymer system is an alternative local drug delivery technique
      to obtain and maintain high tissue levels of the drug at the site of vascular
      injury. To determine if local periadventitial delivery of dexamethasone decreases
      neointimal proliferation after balloon vascular injury, in three groups of
      Sprague-Dawley rats, 5% dexamethasone, 0.5% dexamethasone, and placebo silicone
      polymers were implanted around the left common carotid artery after balloon
      injury. In a fourth group, placebo polymers were implanted without balloon
      injury. Dexamethasone serum and tissue levels after polymer implantation were
      significantly higher in the 5% dexamethasone group compared with the 0.5%
      dexamethasone group. There was no neointima formation in any of the arterial
      segments covered with placebo polymers for 3 wk, but without balloon injury. In
      the arterial segments covered by the 5 and 0.5% dexamethasone polymers, there was
      a 76 and 75% reduction in intima/media ratios, respectively, compared with the
      placebo group (5% dexamethasone, 0.26 +/- 0.04; 0.5% dexamethasone, 0.27 +/-
      0.03; placebo, 1.09 +/- 0.16, respectively; P < 0.0001). These results suggest
      that: (a) silicone polymers wrapped around the common carotid arteries for 3 wk
      did not, without balloon injury, stimulate neointimal proliferation in the rat
      model; (b) the activity of the drug-eluting polymer for suppressing intimal
      proliferation was chiefly, but not exclusively, site specific; and (c)
      transadventitial local delivery of dexamethasone at two different doses markedly
      inhibits neointimal proliferation after balloon vascular injury.

PMID- 8132765
TI  - Insulin-like growth factor-I and platelet-derived growth factor-BB induce
      directed migration of human arterial smooth muscle cells via signaling pathways
      that are distinct from those of proliferation.
AB  - Directed migration or chemotaxis of arterial smooth muscle cells (SMC)
      contributes to intimal SMC accumulation, a key event in the development of
      atherosclerotic lesions and in restenosis after angioplasty. The present study
      compares and contrasts insulin-like growth factor I (IGF-I) and platelet-derived
      growth factor (PDGF-BB) as chemoattractants and mitogens for human arterial SMC.
      Compared with PDGF-BB, IGF-I is a weaker SMC mitogen. Thus, PDGF-BB, but not IGF
      I, evokes a strong and rapid activation of mitogen-activated protein (MAP) kinase
      kinase and MAP kinase. However, IGF-I is a potent stimulator of directed
      migration of human arterial SMC, as measured in a Boyden chamber assay. The half
      maximal concentration for migration is similar to the Kd for IGF-I receptor
      interaction. An IGF-I receptor-blocking antibody blocks the effects of IGF-I, IGF
      II, and insulin, indicating that the effects are indeed mediated through the IGF
      I receptor. The maximal effect of IGF-I on directed migration ranges between 50%
      and 100% of the effect of PDGF-BB, the strongest known chemoattractant for SMC.
      The ability of IGF-I and PDGF-BB to induce chemotaxis coincides with their
      ability to stimulate phosphatidylinositol turnover, diacylglycerol formation, and
      intracellular Ca2+ flux and suggests that these signaling pathways, but not
      activation of the MAP kinase cascade, are required for chemotaxis of human
      arterial SMC.

PMID- 8132766
TI  - Sodium/calcium exchange modulates intracellular calcium overload during
      posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin
      loaded ferret ventricular muscles.
AB  - We tested the hypothesis that the intracellular Ca2+ overload of ventricular
      myocardium during the period of posthypoxic reoxygenation is mediated by
      transsarcolemmal Ca2+ influx via Na+/Ca2+ exchange. In aequorin-loaded, ferret
      right ventricular papillary muscles, blockers of the sarcolemmal and the
      sarcoplasmic reticulum Ca2+ channels, slowed the Cai2+ transient, producing a
      convex ascent during membrane depolarization, followed by a concave descent
      during repolarization. The magnitude of the Cai2+ transient was affected by
      changes in the membrane potential, Nai+, Nao+, and Cao2+, and was blocked by
      Ni2+, or dichlorbenzamil. The calculated Na+/Ca2+ exchange current was in the
      reverse mode (Ca2+ influx) during the ascending phase of the Cai2+ transient, and
      was abruptly switched to the forward mode (Ca2+ efflux) at repolarization,
      matching the time course of the Cai2+ transient. During hypoxic superfusion, the
      Cai2+ transient was abbreviated, which was associated with a shorter action
      potential duration. In contrast, immediately after reoxygenation, the Cai2+
      transient increased to a level greater than that of the control, even though the
      action potential remained abbreviated. This is the first demonstration on a beat
      to-beat basis that, during reoxygenation, Ca2+ influx via Na+/Ca2+ exchange is
      augmented and transports a significant amount of Ca2+ into the ventricular
      myocardial cell. The activation of the exchanger at the time of reoxygenation
      appears to be mediated by Nai+ accumulation, which occurs during hypoxia.

PMID- 8132767
TI  - Angiotensinogen as a risk factor for essential hypertension in Japan.
AB  - A common molecular variant of angiotensinogen (AGT), the precursor of the potent
      vasoactive hormone angiotensin II, has been incriminated as a marker for a
      genetic predisposition to essential hypertension in Caucasians (Jeunemaitre, X.,
      F. Soubrier, Y. V. Kotelevtsev, R. P. Lifton, C. S. Williams, A. Charru, S. C.
      Hunt, P. N. Hopkins, R. R. Williams, J. M. Lalouel, and P. Corvol. 1992. Cell.
      71:169-180). We now show that the same variant, T235, is associated with
      essential hypertension in Japanese patients. The observation of this association
      in a distinct, ethnically homogeneous population further substantiates an
      involvement of angiotensinogen in the pathogenesis of essential hypertension and
      has physiological, epidemiological, and evolutionary implications.

PMID- 8132768
TI  - Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher
      disease.
AB  - Gaucher disease (GD; glucosylceramidosis) is caused by a deficient activity of
      the enzyme glucocerebrosidase (GC). Clinical manifestations are highly variable
      and cannot be predicted accurately on the basis of the properties of mutant GC.
      Analysis of secondary abnormalities, such as elevated plasma levels of some
      hydrolases, may help to increase insight into the complicated pathophysiology of
      the disease and could also provide useful disease markers. The recent
      availability of enzyme supplementation therapy for GD increases the need for
      markers as early predictors of the efficacy of treatment. We report the finding
      of a very marked increase in chitotrisidase activity in plasma of 30 of 32
      symptomatic type 1 GD patients studied: the median activity being > 600 times the
      median value in plasma of healthy volunteers. In three GC-deficient individuals
      without clinical symptoms, only slight increases were noted. Chitotriosidase
      activity was absent in plasma of three control subjects and two patients. During
      enzyme supplementation therapy, chitotriosidase activity declined dramatically.
      We conclude that plasma chitotriosidase levels can serve as a new diagnostic
      hallmark of GD and should prove to be useful in assessing whether clinical
      manifestations of GD are present and for monitoring the efficacy of therapeutic
      intervention.

PMID- 8132769
TI  - Human immunodeficiency virus (HIV) nef-specific cytotoxic T lymphocytes in
      noninfected heterosexual contact of HIV-infected patients.
AB  - We report on the detection of HIV-specific cytotoxic T lymphocytes (CTL) among 23
      regular partners of HIV-infected individuals. 15 of the 46 individuals enrolled
      in the study were positive for HLA-A2.1 typing. Among the 23 contacts studied, 7
      were seropositive and 16 were seronegative on repeated tests. None of the 16
      seronegative contacts were positive for p24 antigenemia nor were they positive by
      the lymphocytes coculture assay, although, in two instances HIV-1 DNA could be
      detected by PCR (in one case using a gag SK 38/39 primer, and in the other using
      a primer for the pol P3/P4 primer). These two individuals remained seronegative
      for 18 and 36 mo, respectively. HIV-specific cytotoxicity was performed in the 15
      HLA-A2.1 subjects (7 indexes, 2 seropositive contacts, and 6 seronegative
      contacts) and in 4 HLA-matched HIV negative donors. CTL specific for env, gag, or
      nef proteins could not be detected in unstimulated bulk cultures of peripheral
      blood lymphocytes in any of the six seronegative contacts. However, using a
      limiting dilution assay we found an usually high frequency of HIV nef-specific
      CTL precursors (CTLp) for HIV env and gag was very similar to that observed in
      seronegative HLA-matched healthy donors. Because no presence of HIV could be
      demonstrated in these individuals, these findings argue against the possibility
      of a silent HIV infection and suggest that a CTL response against nef may be
      involved in a rapid and effective clearance of the virus after sexual exposure.

PMID- 8132770
TI  - Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo.
AB  - Keratinocyte growth factor (KGF) administered as a single intratracheal injection
      causes a prominent dose-dependent proliferation of type II alveolar epithelial
      cells in the lungs of adult rats. The increase in mitotically active alveolar
      cells histologically appears as a micropapillary epithelial cell hyperplasia
      after 2 d and peaks after 3 d in the form of monolayers of cuboidal epithelial
      cells lining alveolar septae. Proliferating cell nuclear antigen
      immunohistochemistry confirmed the profound proliferative response induced by
      KGF. The hyperplastic alveolar lining cells contain immunoreactive surfactant
      protein B and are ultrastructurally noted to contain lamellar inclusions
      characteristic of surfactant-producing type II pneumocytes. Mild focal
      bronchiolar epithelial hyperplasia is noted but is much less striking than the
      proliferation of type II pneumocytes. Large airways are unaffected by KGF. Daily
      intravenous injection of KGF is also able to cause pneumocyte proliferation. The
      normal adult rat lung constitutively expresses both KGF and KGF receptor mRNA,
      suggesting that endogenous KGF may be implicated in the paracrine regulation of
      the growth of pneumocytes. In conclusion, KGF rapidly and specifically induces
      proliferation and differentiation of type II pneumocytes in the normal adult
      lung.

PMID- 8132771
TI  - Defective fluid transport by cystic fibrosis airway epithelia.
AB  - Cystic fibrosis (CF) airway epithelia exhibit defective transepithelial
      electrolyte transport: cAMP-stimulated Cl- secretion is abolished because of the
      loss of apical membrane cystic fibrosis transmembrane conductance regulator
      (CFTR) Cl- channels, and amiloride-sensitive Na+ absorption is increased two- to
      threefold because of increased amiloride-sensitive apical Na+ permeability. These
      abnormalities are thought to alter respiratory tract fluid, thereby contributing
      to airway disease, the major source of mortality in this genetic disease.
      However, the underlying hypothesis, that fluid transport is abnormal in CF airway
      epithelia, has not been tested. Most conjecture about fluid transport is based on
      measurements of Na+ and Cl- transport performed under short circuit conditions in
      Ussing chambers. But such studies differ from in vivo conditions in that
      transepithelial voltage and mucosal fluid composition are held constant.
      Therefore, we measured fluid transport and mucosal electrolyte composition in
      primary cultures of CF airway epithelia without holding transepithelial voltage
      and ion concentration gradients at zero. In normal epithelia, cAMP agonists plus
      amiloride stimulated NaCl and fluid secretion. In CF epithelia, cAMP agonists
      failed to stimulate fluid or electrolyte secretion, changes consistent with the
      loss of CFTR Cl- channels. But in striking contrast to predictions based on
      Ussing chamber studies, CF epithelia absorbed fluid at a rate no greater than
      normal epithelia. Moreover, amiloride, which inhibits Na+ channels, failed to
      inhibit fluid absorption by CF epithelia. These results have important
      implications for understanding the pathogenesis of CF airway disease and for the
      design and evaluation of therapy.

PMID- 8132772
TI  - Induction of immune unresponsiveness to concordant islet xenografts by
      intrahepatic preimmunization and transient immunosuppression.
AB  - Streptozotocin-induced, diabetic mice (C57BL/6) were preimmunized by injecting 25
      low temperature, cultured Wistar-Furth (WF) rat islets into the portal vein, and
      the recipients received one injection of mouse and rat antilymphocyte sera. 3 wk
      later, fresh WF islets were transplanted under the kidney capsule of the
      preimmunized recipients, and normoglycemia was maintained in all 13 recipients
      for 60 d. Removal of the grafts at 60 d returned the mice to a diabetic state.
      Transplants of fresh WF islets under the kidney capsule without pretreatment of
      the recipients had a mean survival time of 16.5 +/- 2.5 d. These findings
      demonstrate that immune unresponsiveness can be achieved across a concordant,
      islet xenograft barrier within 3 wk after intrahepatic preimmunization with a
      small number of donor rat islets and transient immunosuppression with
      antilymphocyte sera.

PMID- 8132773
TI  - Identification of somatostatin receptor subtypes and an implication for the
      efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine
      tumors.
AB  - The presence of somatostatin receptors has been demonstrated in various endocrine
      tumors as well as in normal tissues. We recently have cloned five human
      somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a
      tissue-specific manner. In this study, we have determined the somatostatin
      receptor subtypes expressed in various endocrine tumors using a reverse
      transcriptase polymerase chain reaction method. In two cases of glucagonoma and
      its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5
      mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were
      detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not
      detected in two cases, indicating a heterogeneous expression of SSTR subtypes in
      insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat
      pancreatic islets, is not expressed in normal human pancreatic islets, while
      SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma,
      SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to
      that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were
      detected. We have also found that human SSTR2 shows a high affinity for SMS 201
      995, which has been used clinically for the treatment of endocrine tumors. Since
      SMS 201-995 was effective in the treatment of a patient with glucagonoma in which
      SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which
      SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995
      may depend, at least in part, on the expression of SSTR2 in tumors.

PMID- 8132774
TI  - Molecular cloning, chromosomal localization, and functional characterization of a
      human liver Na+/bile acid cotransporter.
AB  - We have used a cDNA probe from a cloned rat liver Na+/taurocholate cotransporting
      polypeptide (Ntcp) to screen a human liver cDNA library. A 1,599-bp cDNA clone
      that encodes a human Na+/taurocholate cotransporting polypeptide (NTCP) was
      isolated. The human NTCP consists of 349 amino acids (calculated molecular mass
      of 38 kD) and exhibits 77% amino acid homology with the rat Ntcp. In vitro
      translation experiments indicate that the protein is glycosylated and has a
      molecular weight similar to the rat Ntcp. Injection of in vitro transcribed cRNA
      into Xenopus laevis oocytes resulted in the expression of Na(+)-dependent
      taurocholate uptake. Saturation kinetics indicated that the human NTCP has a
      higher affinity for taurocholate (apparent Km = 6 microM) than the previously
      cloned rat protein (apparent Km = 25 microM). NTCP-mediated taurocholate uptake
      into oocytes was inhibited by all major bile acid derivatives (100 microM),
      bumetanide (500 microM), and bromosulphophthalein (100 microM). Southern blot
      analysis of genomic DNA from a panel of human/hamster somatic cell hybrids mapped
      the human NTCP gene to chromosome 14.

PMID- 8132775
TI  - Pancreatic islet production of murine interleukin-10 does not inhibit immune
      mediated tissue destruction.
AB  - IL-10 inhibits macrophage-dependent antigen presentation, cytokine production,
      and generation of allospecific cells in vitro. These findings have lead to the
      widespread expectation that IL-10 may be a useful immunosuppressive agent to
      inhibit allograft rejection or autoimmunity in vivo. We used two experimental
      paradigms to study effects of murine IL-10 on in vivo immune responses. First,
      fetal pancreata or adult pancreatic islets from transgenic mice expressing IL-10
      in pancreatic beta cells (Ins-IL-10 mice) were grafted across the MHC barrier to
      examine if IL-10 could inhibit allograft rejection. Second, Ins-IL-10 mice were
      crossed with transgenic mice expressing lymphocytic choriomeningitis virus (LCMV)
      antigens in pancreatic beta cells. These mice were infected with LCMV to elicit
      autoimmune diabetes, allowing us to ask if IL-10 protects islets from autoimmune
      destruction. We observed that allografts from IL-10-transgenic donors were
      rejected with comparable kinetics to the rejection of control nontransgenic
      allografts, indicating that IL-10 does not inhibit allograft rejection. After
      LCMV infection, IL-10 and LCMV antigen double transgenic mice developed diabetes
      earlier than LCMV antigen single transgenic littermates, suggesting that IL-10
      does not inhibit islet antigen presentation or recognition. Our results contrast
      to in vitro observations and suggest that IL-10 cannot overcome immune-mediated
      tissue destruction within the pancreas.

PMID- 8132776
TI  - Endothelium dependency of contractile activity differs in infant and adult
      vertebral arteries.
AB  - Contractions to serotonin (5-HT) and endothelin-1 (ET-1) in infant (0-2 yr) and
      adult (38-71 yr) vertebral arteries were examined in the presence of either the
      cyclooxygenase inhibitor indomethacin or NG-monomethyl-L-arginine (L-NMMA), an
      inhibitor of nitric oxide production. In addition, endothelium-dependent
      relaxations to acetylcholine were characterized in arteries contracted with
      agonist. The results showed that: (a) Contractions of infant arteries to 5-HT or
      ET-1 decreased to 44 +/- 8% and 27 +/- 13%, respectively, within 10 min.
      Indomethacin or removal of endothelium abolished this decreased response, whereas
      L-NMMA had no effect. (b) Adult arteries produced sustained contractions to 5-HT
      or ET-1 that were unaffected by indomethacin, endothelium denudation, or L-NMMA.
      (c) Endothelium-dependent relaxations to acetylcholine were greater in infant
      than adult arteries and were abolished by indomethacin (but not L-NMMA) in
      infants and L-NMMA (but not indomethacin) in adults. Thus, endothelium-dependent
      responses in infant arteries are attenuated because of increased prostaglandin
      activity not observed in adult tissues. Additionally, there is an age-dependent
      change in the primary mechanism responsible for acetylcholine-induced
      vasodilation. Apparently, endothelium dependency of acetylcholine-induced
      relaxation is highly dependent on cyclooxygenase activity in the infant vertebral
      artery, but in the adult artery, nitric oxide is linked to the vasodilator
      response.

PMID- 8132777
TI  - Immune responses to human immunodeficiency virus type 1 in exposed but uninfected
      individuals: protection or chance?

PMID- 8132778
TI  - Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for
      macrophages in rheumatoid arthritis.
AB  - We have shown that human macrophages (m phi s) play an important role in the
      elaboration of chemotactic cytokines in rheumatoid arthritis (RA) (Koch, A. E.,
      S. L. Kunkel, J. C. Burrows, H. L. Evanoff, G. K. Haines, R. M. Pope, and R. M.
      Strieter. 1991. J. Immunol. 147:2187; Koch, A. E., S. L. Kunkel, L. A. Harlow, B.
      Johnson, H. L. Evanoff, G. K. Haines, M. D. Burdick, R. M. Pope, and R. M.
      Strieter. 1992. J. Clin. Invest. 90:772; Koch, A. E., P. J. Polverini, S. L.
      Kunkel, L. A. Harlow, L. A. DiPietro, V. M. Elner, S. G. Elner, and R. M.
      Strieter. 1992. Science (Wash. DC). 258:1798). Recently, m phi inflammatory
      protein-1 (MIP-1 alpha), a cytokine with chemotactic activity for m phi s and
      neutrophils (PMNs), has been described. We have examined the production of MIP-1
      alpha using sera, synovial fluid (SF), and synovial tissue (ST) from 63 arthritic
      patients. MIP-1 alpha was higher in RA SF (mean, 29 +/- 8 ng/ml [SE]) compared
      with other forms of arthritis (2.8 +/- 1.7), or osteoarthritis (0.7 +/- 0.4; P <
      0.05). RA SF MIP-1 alpha was greater than that found in either RA or normal
      peripheral blood (PB) (P < 0.05). Anti-MIP-1 alpha neutralized 36 +/- 3% (mean +/
      SE) of the chemotactic activity for m phi s, but not PMNs, found in RA SFs. RA
      SF and PB mononuclear cells produced antigenic MIP-1 alpha. Mononuclear cell MIP
      1 alpha production was augmented with phytohemagglutinin or LPS. Isolated RA ST
      fibroblast production of antigenic MIP-1 alpha was augmented upon incubation of
      cells with LPS, and to a lesser extent with tumor necrosis factor-alpha. Isolated
      RA ST m phi s expressed constitutive MIP-1 alpha mRNA and antigenic MIP-1 alpha.
      Using ST immunohistochemistry, MIP-1 alpha+ cells from RA compared with normal
      were predominantly m phi s and lining cells (P < 0.05). These results suggest
      that MIP-1 alpha plays a role in the selective recruitment of m phi s in synovial
      inflammation associated with RA.

PMID- 8132779
TI  - Rapid desensitization of neonatal rat liver beta-adrenergic receptors. A role for
      beta-adrenergic receptor kinase.
AB  - Exposure of beta-adrenergic receptors (BAR) to agonists often leads to a rapid
      loss of receptor responsiveness. The proposed mechanisms of such rapid receptor
      desensitization include receptor phosphorylation by either cAMP-dependent protein
      kinase or the specific beta-adrenergic receptor kinase (BARK), leading to
      functional uncoupling from adenylyl cyclase and sequestration of the receptors
      away from the cell surface. To evaluate the physiological role of such
      mechanisms, we have investigated whether rapid regulation of BAR occurs in the
      neonatal rat liver immediately after birth, a physiological situation
      characterized by a dramatic but transient increase in plasma catecholamines. We
      have detected a rapid, transient uncoupling of liver plasma membrane BARs from
      adenylyl cyclase (corresponding to a desensitization of approximately 45%) within
      the first minutes of extrauterine life, followed by a transient sequestration of
      approximately 40% of the BARs away from the plasma membrane. In agreement with
      such pattern of desensitization, we have detected (by enzymatic and immunological
      assays) rapid changes in BARK specific activity in different neonatal rat liver
      subcellular fractions that take place within the same time frame of BAR
      uncoupling and sequestration. Our results provide new evidence on the potential
      role of BAR desensitization mechanisms in vivo and suggest that they are involved
      in modulating catecholamines actions at the moment of birth. Furthermore, our
      data indicate that in addition to its suggested role as a rapid modulator of
      adrenergic receptor function at synapse, rapid BARK-mediated receptor regulation
      may have functional relevance in other tissues in response to high circulating or
      local levels of agonists.

PMID- 8132780
TI  - 17 beta-Estradiol inhibits expression of human interleukin-6 promoter-reporter
      constructs by a receptor-dependent mechanism.
AB  - We previously reported that 17 beta-estradiol inhibits cytokine-stimulated
      bioassayable IL-6 and the steady-state level of IL-6 mRNA. To determine the
      molecular basis of this effect, the transient expression of chloramphenicol
      acetyltransferase (CAT) reporter plasmid driven by the human IL-6 promoter was
      studied here in HeLa or murine bone marrow stromal cells (MBA 13.2). 17 beta
      estradiol (10(-8) M) completely suppressed stimulated CAT expression in HeLa
      cells cotransfected with IL-6/CAT constructs and a human estrogen receptor (hER)
      expression plasmid; but had no effect on reporter expression in HeLa cells not
      transfected with hER. 17 beta-estradiol also inhibited stimulated expression in
      MBA 13.2 cells (which express the estrogen receptor constitutively) without the
      requirement of cotransfection of the hER plasmid. The hormonal effects were
      indistinguishable between constructs containing a 1.2-kb fragment of the 5'
      flanking region of the IL-6 gene or only the proximal 225-bp fragment. However,
      yeast-derived recombinant hER did not bind to the 225-bp segment in DNA band
      shift assays, nor did the 225-bp fragment compete for binding of an estrogen
      response element oligonucleotide to yeast-derived estrogen receptor. These data
      suggest that 17 beta-estradiol inhibits the stimulated expression of the human IL
      6 gene through an estrogen receptor mediated indirect effect on the
      transcriptional activity of the proximal 225-bp sequence of the promoter.

PMID- 8132781
TI  - Ca2+ transient decline and myocardial relaxation are slowed during low flow
      ischemia in rat hearts.
AB  - The mechanisms that impair myocardial relaxation during ischemia are believed to
      involve abnormalities of calcium handling. However, there is little direct
      evidence to support this hypothesis. Therefore, we sought to determine whether
      the time constant of cytosolic calcium ([Ca2+]c) decline (tau Ca) was increased
      during low flow ischemia, and if there was a relationship between the time
      constant of left ventricular pressure decline (tau P) and tau Ca. Isolated
      perfused hearts were studied using indo-1 fluorescence ratio as an index of
      [Ca2+]c.tau P was used as an index of myocardial relaxation. The time constant of
      decline of the indo-1 ratio increased from 74 +/- 5 ms to 95 +/- 4, 144 +/- 10,
      and to 204 +/- 16 ms when coronary flow was reduced was reduced to 50, 20, and
      10% of control, respectively. Indo-1 transients were calibrated to calculate tau
      Ca. tau Ca increased from 67 +/- 6 ms to 108 +/- 9 and 158 +/- 19 ms when
      coronary flow was reduced to 20 and 10% of control, respectively. There was a
      linear relationship between tau Ca and tau P (r = 0.82). These data support the
      hypothesis that during low flow ischemia, impaired myocardial relaxation may be
      caused by slowing of [Ca2+]c decline.

PMID- 8132782
TI  - Cellular distribution of insulin-degrading enzyme gene expression. Comparison
      with insulin and insulin-like growth factor receptors.
AB  - Insulin-degrading enzyme (IDE) hydrolyzes both insulin and IGFs and has been
      proposed to play a role in signal termination after binding of these peptides to
      their receptors. In situ hybridization was used to investigate the cellular
      distribution of IDE mRNA and to compare it with insulin receptor (IR) and IGF-I
      receptor (IGFR) gene expression in serial thin sections from a variety of tissues
      in embryonic and adult rats. IDE mRNA is highly abundant in kidney and liver,
      tissues known to play a role in insulin degradation. IDE and IR mRNAs are highly
      coexpressed in brown fat and liver. The highest level IDE gene expression, on a
      per cell basis, is found in germinal epithelium. IDE and IGFR mRNAs are
      colocalized in oocytes, while IDE is colocalized with the IGF-II receptor in
      spermatocytes, suggesting that IDE may be involved with degradation of IGF-II in
      the testis. In summary, IDE expression demonstrates significant anatomical
      correlation with insulin/IGF receptors. These data are compatible with a role for
      IDE in degrading insulin and IGFs after they bind to and are internalized with
      their respective receptors and may also suggest a novel role for IDE in germ
      cells.

PMID- 8132783
TI  - Adenosine receptors mediate synergistic stimulation of glucose uptake and
      transport by insulin and by contractions in rat skeletal muscle.
AB  - The role of adenosine receptors in the regulation of muscle glucose uptake by
      insulin and contractions was studied in isolated rat hindquarters that were
      perfused with a standard medium containing no insulin or a submaximal
      concentration of 100 microU/ml. Adenosine receptor antagonism was induced by
      caffeine or 8-cyclopentyl-1,3-dipropylxantine (CPDPX). Glucose uptake and
      transport were measured before and during 30 min of electrically induced muscle
      contractions. Caffeine nor CPDPX affected glucose uptake in resting hindquarters.
      In contrast, the contraction-induced increase in muscle glucose uptake was
      inhibited by 30-50% by caffeine, as well as by CPDPX, resulting in a 20-25%
      decrease in the absolute rate of glucose uptake during contractions, compared
      with control values. This inhibition was independent of the rate of perfusate
      flow and only occurred in hindquarters perfused with insulin added to the medium.
      Thus, adenosine receptor antagonism inhibited glucose uptake during simultaneous
      exposure to insulin and contractions only. Accordingly, caffeine inhibited 3-O
      methylglucose uptake during contractions only in oxidative muscle fibers that are
      characterized by a high sensitivity to insulin. In conclusion, the present data
      demonstrate A1 receptors to regulate insulin-mediated glucose transport in
      contracting skeletal muscle. The findings provide evidence that stimulation of
      sarcolemmic adenosine receptors during contractions is involved in the
      synergistic stimulation of muscle glucose transport by insulin and by
      contractions.

PMID- 8132784
TI  - Programmed death of T cells in human immunodeficiency virus infection. No
      correlation with progression to disease.
AB  - Programmed death of T cells has been proposed as one of the mechanisms by which
      HIV affects immune functions in stages of infection where the number of infected
      cells is low. Indeed, in HIV-infected individuals both CD4+ and CD8+ T cells are
      primed for programmed cell death, which can be enhanced by polyclonal
      stimulation. Here, we investigated programmed death of T cells in all stages of
      HIV infection, including acute infection. In individuals with primary infection
      the number of T cells dying due to apoptosis was much higher than in the
      asymptomatic phase of infection and paralleled increased numbers of CD8+ cells.
      In asymptomatic HIV-infected individuals, cells were dying in increased
      percentages compared with noninfected controls, although at much lower numbers
      than during acute infection. Death of T cells was not quantitatively correlated
      with CD4+ T cell numbers or appearance of more cytopathic, syncytium-inducing HIV
      variants. Analysis of the phenotype of cells undergoing apoptosis revealed that
      cell death was not confined to a specific T cell subset nor correlated with
      expression of certain T cell activation markers. Our results imply that the
      extent of programmed cell death of T cells in HIV infection does not correlate
      with progression to disease.

PMID- 8132787
TI  - Coexisting calcified inferior vena cava thrombus and adrenal hemorrhage in the
      neonate: report of three cases.
AB  - Coexisting calcified inferior vena cava (IVC) thrombus and adrenal hemorrhage are
      uncommon in children. We present three such cases diagnosed by ultrasound in
      three boys who were born after 41-, 38-, and 38-week gestations, respectively. In
      all cases the pregnancy and delivery were unremarkable. The birthweight was 3,630
      g, 3,210 g, and 3,390 g, respectively. Left adrenal hemorrhage occurred in all
      cases. Associated left renal vein thrombus occurred in two cases. The mean
      followup was 8.5 years. In two cases ultrasound showed persistence of a calcified
      thrombus and residual stenosis of the IVC. In the third case the IVC thrombus had
      almost disappeared.

PMID- 8132785
TI  - Age- and gender-related changes in the distribution of osteocalcin in the
      extracellular matrix of normal male and female bone. Possible involvement of
      osteocalcin in bone remodeling.
AB  - With increasing age, bone undergoes changes in remodeling that ultimately
      compromise the structural integrity of the skeleton. The presence of osteocalcin
      in bone matrix may alter bone remodeling by promoting osteoclast activity.
      Whether age- and/or gender-related differences exist in the distribution of
      osteocalcin within individual bone remodeling units is not known. In this study,
      we determined the immunohistochemical distribution of osteocalcin in the
      extracellular matrix of iliac crest bone biopsies obtained from normal male and
      female volunteers, 20-80 yr old. Four different distribution patterns of
      osteocalcin within individual osteons were arbitrarily defined as types I, II,
      III, or IV. The frequency of appearance of each osteon type was determined as a
      percent of the total osteons per histologic section. The proportion of osteons
      that stained homogeneously throughout the concentric lamellae (type I) decreased
      in females and males with increasing age. The proportion of osteons that lack
      osteocalcin in the matrix immediately adjacent to Haversian canals (type III)
      increased in females and males with age. Osteons staining intensely in the matrix
      adjacent to Haversian canals (type II) increased in females and was unchanged in
      aging males. Osteons that contained osteocalcin-positive resting lines (type IV)
      increased in bone obtained from males with increasing age but were unchanged in
      females. Sections of bone immunostained for osteopontin (SPP-I), osteonectin, and
      decorin did not reveal multiple patterns or alterations in staining with gender
      or increasing age. We suggest that the morphology of individual bone remodeling
      units is heterogeneous and the particular morphologic pattern of osteocalcin
      distribution changes with age and gender. These results suggest that differences
      in the distribution of osteocalcin in bone matrix may be responsible, in part,
      for the altered remodeling of bone associated with gender and aging.

PMID- 8132786
TI  - Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma
      and low density lipoprotein exposed to oxidative stress in vitro.
AB  - F2-isoprostanes are prostaglandin F2-like compounds that are known to be formed
      in vivo by free radical oxidation of arachidonyl-containing lipids, and their
      plasma levels have been suggested as indicators of in vivo oxidative stress. As
      oxidation of LDL, a likely causal factor in atherosclerosis, involves lipid
      peroxidation, we investigated whether F2-isoprostanes are formed in plasma and
      LDL exposed to oxidative stress, and how F2-isoprostane formation is related to
      endogenous antioxidant status. In plasma exposed to aqueous peroxyl radicals,
      lipid hydroperoxides and esterified F2-isoprostanes were formed simultaneously
      after endogenous ascorbate and ubiquinol-10 had been exhausted, despite the
      continued presence of urate, alpha-tocopherol, beta-carotene, and lycopene. In
      isolated LDL exposed to aqueous peroxyl radicals or Cu2+, consumption of
      endogenous ubiquinol-10 and alpha-tocopherol was followed by rapid formation and
      subsequent breakdown of lipid hydroperoxides and esterified F2-isoprostanes, and
      a continuous increase in LDL's electronegativity, indicative of atherogenic
      modification. In Cu(2+)-exposed LDL, the decrease in esterified F2-isoprostane
      levels was paralleled by the appearance of free F2-isoprostanes, suggesting that
      hydrolysis by an LDL-associated activity had occurred. Our data suggest that F2
      isoprostanes are useful markers of LDL oxidation in vivo. As F2-isoprostanes are
      potent vasoconstrictors and can modulate platelet aggregation, their formation in
      LDL demonstrated here may also have important implications for the etiology of
      cardiovascular disease.

PMID- 8132788
TI  - Transabdominal ultrasonographic evaluation of endometrial thickness in clomiphene
      citrate-stimulated cycles in relation to conception.
AB  - The possible antiestrogenic effect of clomiphene citrate on endometrial growth
      was assessed by serial transabdominal ultrasonographic measurements in 46 women
      with unexplained infertility. A significantly higher (p < 0.05) rate of
      endometrial growth was observed in the 8 women who conceived compared with the 38
      women who failed to conceive. A thicker endometrium (4.6 +/- 0.3 mm) was observed
      from the third day before ovulation as well as a higher average growth rate in
      the three days prior to ovulation (0.7 +/- 0.1 mm/day) in the group that achieved
      pregnancy compared to a lower endometrium (2.1 +/- 0.2 mm) from the third day
      before ovulation and a slower growth rate in the three days prior to ovulation
      (0.2 +/- 0.0 mm/day) in the group that did not achieve pregnancy (p < 0.05).
      These data suggest that clomiphene citrate may exert an antiestrogenic effect on
      the endometrium, and thus interfere with implantation.

PMID- 8132789
TI  - Ultrasound therapy for malignant tumors: a conceptual assessment.

PMID- 8132790
TI  - Intracystic carcinoma of the male breast.

PMID- 8132791
TI  - Metastatic colonic adenocarcinoma simulating primary ovarian neoplasm in
      transvaginal Doppler sonography.

PMID- 8132792
TI  - Ultrasonic diagnosis of torsion of the wandering spleen.

PMID- 8132793
TI  - Carcinoid tumor of the appendix: ultrasound findings in two cases.

PMID- 8132794
TI  - Spontaneous remission of parathyroid adenoma followed with ultrasonographic
      examinations.

PMID- 8132795
TI  - Usefulness of Doppler sonography in monitoring transjugular intrahepatic
      portosystemic shunts.

PMID- 8132796
TI  - Ultrasound diagnosis of a prepyloric diaphragm.

PMID- 8132797
TI  - Atypical sound transmission in an angiomyolipoma.

PMID- 8132798
TI  - Application of the Valsalva maneuver to facilitate sonographic-guided
      catheterization of the subclavian vein.

PMID- 8132799
TI  - Ultrasonic evaluation of benign and malignant nodules in echographically
      multinodular thyroids.
AB  - In 165 patients with ultrasound findings of multinodular thyroids in whom thyroid
      resection was performed, sonographic features and pathohistologic findings of
      removed nodules were analyzed. Of 426 nodules removed, 70 were carcinomas and 356
      benign. Carcinomas are more often hypoechogenic (p < 0.01) and contain nodular
      calcifications (p < 0.01), while benign nodules are more often iso-hyperechogenic
      (p < 0.01), showing intranodular cystic degenerative changes (p < 0.01) and
      perinodular hypoechogenic rim (p < 0.01). Mean diameter of carcinomatous nodules
      is lower than in benign nodules (p = 0.022). The relative proportion of malignant
      nodules is highest in the upper halves of thyroid lobes (p < 0.01). Although
      certain sonographic signs increase the likelihood of a given lesion being
      malignant or benign, the lack of absolute specificity in the ultrasound
      evaluation of thyroid nodules was confirmed.

PMID- 8132800
TI  - Measurement of placental volume with real-time ultrasound in mid-pregnancy.
AB  - A new method to measure placental volume in mid-pregnancy using real-time
      ultrasound is described. The method is an adaptation of the B-mode parallel
      planimetric technique. The mean error of in vitro measurements on 45 balloons
      (mean volume 186 mL range: 88-485 mL) was -2.24 mL, standard deviation 6.76 mL.
      The error standard deviation of in vivo placental volume measurements was 16.4 mL
      (volume range: 173-396.5 mL). Placental measurements were made on 175 women
      between 14.3 weeks and 21.4 weeks, menstrual age (MA) and a smooth centile curve
      derived. Median volume increased linearly from 144 to 329 mL. The size of the
      ultrasound probe limits the technique to use before 20 weeks, MA.

PMID- 8132801
TI  - Ultrasonography as a primary diagnostic tool in patients with inflammatory
      disease and tumors of the small intestine and large bowel.
AB  - In 240 patients with predefined indications, the validity of ultrasound imaging
      as a primary diagnostic procedure was examined prospectively. Ultrasonography
      revealed normal intestinal findings in 150 patients and pathological lesions in
      90 subjects. All patients underwent subsequent endoscopic, radiological, or
      surgical examination. In 7 patients with Crohn's disease and in 2 patients with
      radiation colitis, the ultrasound findings were false-negative. In the other 9
      cases, ultrasonography suggested false-positive results. Ultrasonographic
      examination of the small intestine and large bowel had a very high overall
      validity, with a sensitivity of 90% and specificity of 94%.

PMID- 8132802
TI  - Neurosonographic imaging of small-for-gestational-age neonates exposed and not
      exposed to cocaine and cytomegalovirus.
AB  - We sought to prospectively identify the role of neurosonography in the evaluation
      of a consecutive group of small-for-gestational-age (SGA) neonates, and also to
      identify the association of neurosonographic findings with cocaine exposure and
      cytomegalovirus (CMV) infection. Neurosonographic imaging was performed in 180
      SGA neonates within 72 hours of birth. Urine samples were screened for CMV and
      cocaine metabolites (CM) in all cases. Sixty-five neonates (37.5%) had an
      abnormal neurosonographic appearance. Nine neonates were positive for CMV and 31
      neonates were positive for CM. Focal echolucencies (27), ventricular dilation
      (27), and subependymal hemorrhages (12) were the most common neurosonographic
      abnormalities. The first two were more common with CM (p < .05). An abnormal
      neurosonographic pattern was seen more often in SGA neonates with CM (54.8%, 17
      of 31; p < .05) and CMV (67%, 6 of 9; p < .01) as compared with the rest (32.6%,
      44 of 135; p < .01). Among those without CM or CMV, prematurity was associated
      with an increased risk for abnormality (p < .001 between groups), specifically
      subependymal hemorrhage, ventricular dilation, and porencephalic cysts. Five CMV
      positive neonates showed periventricular, echogenic foci mainly in the area of
      the frontal horn. Two new findings with SGA were caudate nucleus echogenicity and
      a "moth-eaten" appearance of the thalamus, each found in three infants.
      Neurosonographic imaging is useful in the evaluation of SGA neonates. Focal
      echolucencies and caudate echogenicity suggest maternal cocaine use, and
      periventricular echogenic foci strongly suggest fetal CMV infection.

PMID- 8132803
TI  - Joint Working Group on quality assurance in pathology: guidance to the
      professions.

PMID- 8132804
TI  - Audit of deaths from cervical cancer: proposal for an essential component of the
      National Screening Programme.
AB  - AIMS: To ascertain the type and relative frequency of major factors associated
      with deaths from cervical cancer. METHODS: Deaths from cervical cancer in
      Rotherham district for the period 1989-1991 were subjected to multifactorial
      audit by reviewing laboratory, hospital, and general practitioner records;
      together with, when appropriate, re-screening of cytology smears. This period
      represented the three to five years after a computerised National Screening
      Programme (NSP) had been implemented with a five year recall interval. RESULTS:
      Thirty six deaths were identified. The average age of death was 59 years with 39%
      occurring in those over 65. Only 6% of cases presented as a result of a cervical
      smear, comprising 3% derived from the NSP and 3% by chance. Forty seven per cent
      of cases in which the patient had died had no record of a previous smear
      invitation; 22% of patients were under 65 years and 25% 65 or over. Those under
      65 had presented before the appropriate age band had been called. A non-response
      to a cervical smear invitation was identified in 22%. In 25% of cases a true
      negative smear had been reported one to eight years previously (average 4.8
      years). An inappropriate laboratory diagnosis was identified in 17% of cases.
      Fourteen per cent represented false negative smears and 8% comprised inadequate
      smears that had been reported as negative. Inappropriate clinical diagnosis or
      management was identified in 19% of cases. In 22% two or more contributory
      factors were identified in the same patient. CONCLUSIONS: Areas highlighted by
      the audit warranting further attention included the targeting of women over 65
      with no cytology record; those not responding to smear invitations; laboratory
      performance; clinical acumen; and the reasons for true negative cervical smears.
      Multifactorial audit of all deaths from cervical cancer should be advocated
      nationally to assess and improve the effectiveness of the NSP.

PMID- 8132805
TI  - Encoded latent membrane protein 1 of Epstein-Barr virus on follicular dendritic
      cells in residual germinal centres in Hodgkin's disease.
AB  - AIMS: To determine if there is an association between Epstein-Barr virus (EBV)
      infection and Hodgkin's disease. METHODS: Fifty cases of Hodgkin's disease and 25
      reactive lymph nodes were screened for the presence of EBV-RNA (EBER) using in
      situ hybridisation, and for the expression of EBV encoded latent membrane protein
      1 (LMP-1) by immunohistochemistry. RESULTS: In 42% of the cases of Hodgkin's
      disease, EBER was detected in the nuclei of the malignant cells, and in LMP-1
      expression was found 36%. Both EBER and LMP-1 positivity were seen in 34% of the
      cases. An additional finding was the presence of LMP-1 on follicular dendritic
      cells in residual germinal centres in two cases of Hodgkin's disease. EBER was
      not detected in these germinal centres. In reactive lymph nodes only occasional
      EBER positive, small, lymphoid cells were found, without LMP-1 expression.
      CONCLUSIONS: These results show a strong correlation between the presence of EBER
      and the LMP-1 expression in the Reed-Sternberg cells. They corroborate a role for
      EBV in at least some cases of Hodgkin's disease. LMP-1 is probably presented as
      an immune complex in the germinal centres, as part of an immune response against
      EBV.

PMID- 8132806
TI  - Relation of CD30 expression to survival and morphology in large cell B cell
      lymphomas.
AB  - AIMS: To investigate whether CD30 expression is correlated with anaplastic
      morphology, and whether this correlated with a better survival in large cell B
      cell lymphomas, as has been described for T cell lymphomas. METHODS: CD30
      expression was investigated using frozen sections in a series of 146 large cell B
      cell lymphomas. Clinical data and follow up information were collected from 25
      lymphomas with strong CD30 expression, 30 lymphomas with partial CD30 expression,
      and a control group of 25 lymphomas which did not express CD30. RESULTS:
      Morphological distinction between anaplastic and non-anaplastic tumours was
      difficult. Of the cases with an anaplastic morphology, 50% were CD30 positive, as
      were 24% of the polymorphic centroblastic B cell lymphomas. Only 65% of the
      morphologically non-anaplastic tumours were completely CD30 negative. There was
      no difference in survival among patients with lymphomas expressing CD30 and those
      that did not. Patients with morphologically anaplastic B cell lymphomas did not
      differ in their survivals from those with other high grade B cell lymphomas.
      Clinical stage at presentation was the only variable that was significantly
      associated with survival. CONCLUSIONS: CD30 expression occurs frequently in large
      cell B cell lymphomas and is poorly related to anaplastic morphology.
      Morphological distinction between anaplastic and non-anaplastic tumours is
      difficult. In contrast to T cell lymphomas, CD30 positive B cell lymphomas do not
      show a relatively favourable clinical course. The results presented here raise
      serious doubts as to whether large cell B cell lymphoma, based on the expression
      of CD30 or anaplastic morphology, can really be termed a separate entity.

PMID- 8132807
TI  - Polyploidy in non-neoplastic tissues.
AB  - AIM: To investigate the prevalence and amount of polyploidy in fine needle
      aspiration specimens of the liver, urinary cytospin preparations, and cytospin
      preparations from pleural and peritoneal fluid. METHODS: Cells from 44 liver
      smears, 48 urine specimens, and 46 pleural and peritoneal aspirations were
      examined. After Feulgen restaining the DNA content of 100 randomly selected
      nuclei was determined using a TAS-plus image analysis system, combined with an
      automated microscope. RESULTS: Polyploidy was observed up to 16c in the liver,
      and up to 8c in urothelium and mesothelium. Sixty eight per cent of the liver
      aspirates contained polyploid nuclei. The rate in urothelium was 20.8% and in
      mesothelium 6.5%. CONCLUSIONS: Polyploidy in the liver may be interpreted as
      being associated with tissue differentiation, but the findings in urothelium and
      mesothelium remain of unknown importance.

PMID- 8132808
TI  - ACP Broadsheet No 143: January 1994. Detection of autoantibodies to neutrophil
      cytoplasmic antigens.

PMID- 8132809
TI  - Observer variability in the histopathological reporting of abnormal rectal biopsy
      specimens.
AB  - AIMS: To study the consistency of reporting of abnormal rectal biopsy specimens,
      especially in the differentiation of inflammatory bowel disease from other causes
      of abnormality. METHODS: Sixty rectal biopsy specimens were identified from
      patients presenting with bloody diarrhoea. These were then circulated to the 11
      consultant pathologists in the study who filled in a proforma with a list of 12
      diagnostic categories and 22 features. RESULTS: Forty one of the 60 cases were
      examples of inflammatory bowel disease. In 33 of these cases nine or more
      pathologists had made the diagnosis. Further categorisation into ulcerative
      colitis and Crohn's disease showed better recognition of ulcerative colitis. In
      the 19 cases of non-inflammatory bowel disease recognition of pseudomembranous
      colitis and solitary rectal ulcer syndrome was good, but the results were poorer
      in the case of infective colitis. CONCLUSION: The findings suggest that a group
      of consultant pathologists can differentiate between inflammatory bowel disease
      and other causes of an abnormal rectal biopsy specimen and can also recognise
      pseudomembranous colitis and solitary rectal ulcer syndrome satisfactorily.

PMID- 8132810
TI  - Phenotypic identity of gastric mucous neck cells and mucous cells of cardiac,
      pyloric, and Brunner's glands.
AB  - AIM: To investigate the tissue specificity of a novel monoclonal antibody raised
      to a tissue fraction of normal human liver and which identified certain cells of
      gastric and duodenal mucosa. METHODS: A total of 155 samples of various tissues
      obtained from 100 surgical specimens were fixed in cold ethanol-paraformaldehyde,
      embedded in paraffin wax, and 3 microns sections were studied by
      immunohistochemical and lectin staining procedures. RESULTS: Immunohistochemical
      staining showed a major tissue specific component which was strongly expressed by
      mucous neck cells of the body of the stomach, glands of the cardia and pyloric
      antrum, and by Brunner's glands. Staining for antigen in the periductal glands of
      normal major biliary and pancreatic ducts was variable and relatively weaker. It
      was not detected elsewhere in normal intestine or in the other normal tissues
      tested. Barrett's mucosa of gastric cardia type, and pyloric gland metaplasia in
      the gall bladder and small bowel affected with Crohn's disease stained for the
      antigen. The tissue distribution of the antigen was identical with that of a
      glycoprotein, demonstrated by an induced affinity for concanavalin A following
      treatment of tissue sections with periodic acid. The antigen was not sensitive to
      sialidase. CONCLUSIONS: The tissue component identified (designated here as
      antigen D10) seems to be characteristic of certain differentiated epithelial
      cells derived from that part of foregut giving rise to stomach, duodenum, and
      biliary and pancreatic ducts. The antibody will be of use in investigating
      pathological processes involving tissue differentiation at these sites, and in
      the oesophagus and intestines.

PMID- 8132811
TI  - Seasonal variation in the necropsy incidence of massive pulmonary embolism.
AB  - AIMS: To investigate the seasonal incidence of massive pulmonary embolism at
      necropsy. METHODS: Massive pulmonary embolism was defined as a recent
      thromboembolus occluding the pulmonary trunk or one or both main pulmonary
      arteries and constituting the main cause of death. A total of 4289 necropsies
      carried out at East Birmingham Hospital from 1979 to 1988 was reviewed. The
      number of subjects with massive pulmonary embolism was noted and the accumulated
      percentage for each calendar month was calculated. RESULTS: Massive pulmonary
      embolism was found in 13.02% of necropsies carried out in April; in September and
      October the percentage rose to 14.29 and 14.19, respectively, after falling to
      8.04 and 7.80 in June and July. In January and February the incidence fell again
      to about 9%. CONCLUSIONS: The incidence of massive pulmonary embolism at East
      Birmingham Hospital is highest in the spring and autumn. Investigation of the
      seasonal incidence in arctic and tropical areas would be of interest.

PMID- 8132813
TI  - Impact of rotavirus infection on a paediatric hospital in the east end of London.
AB  - AIMS: To study the impact of confirmed rotavirus infection at a paediatric
      hospital; to use the data to obtain a minimum estimate of the cost of treating
      reported cases of rotavirus in England and Wales. METHODS: Data were obtained on
      all patients with rotavirus over a two year period. Information was collected on
      386 patients with rotavirus infection who were treated at the 120 bed Queen
      Elizabeth Hospital for Children in East London. This included the virus serotype,
      the patient's age, whether they required intravenous infusion, duration of
      hospital stay, numbers of patients treated in the casualty department, and
      numbers who had to be admitted. Treatment costs were obtained from the Finance
      Department of the Hospitals for Sick Children. RESULTS: The minimum cost of
      treating patients, excluding the cost of medical staff at the hospital, was
      estimated to be 95,400 pounds a year. One hundred and forty eight (38%) patients
      were admitted to the wards and a further 49 patients developed symptoms while in
      hospital. Intravenous infusion was required by 18 patients. The mean duration of
      hospital stay was 5.5 days. One hundred and eighty nine (49%) patients were
      treated with oral rehydration solution in casualty, given advice, and sent home.
      Ninety four per cent of the patients were aged under 2 years. The findings were
      comparable with those obtained in a study at Texas Children's Hospital, USA. The
      G serotype (VP7) of rotavirus did not influence the severity of infection.
      CONCLUSION: Rotavirus infections accounted for a significant number of patients
      treated in casualty, admissions to hospital, and bed occupancy in a paediatric
      hospital. The estimated cost of treating reported cases of rotavirus in England
      and Wales is in excess of 6.3 pounds million a year.

PMID- 8132812
TI  - Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic
      gastroduodenal mucosa.
AB  - AIMS: To investigate the expression of interleukin-8 (IL-8) in Helicobacter
      pylori infected normal and neoplastic gastroduodenal mucosa, and in established
      gastric cancer cell lines. METHODS: Immunofluorescence techniques were used to
      localise IL-8 in cryosections of gastric (n = 25) and duodenal (n = 17)
      endoscopic biopsy specimens an in resected gastric tumour tissue samples from 16
      patients. Two gastric cancer cell lines (Kato 3 and MKN 45) were examined for IL
      8 protein expression by immunofluorescence and for the presence of IL-8 mRNA by
      reverse transcription followed by the polymerase chain reaction (RT-PCR).
      RESULTS: IL-8 was localised to the epithelium in histologically normal gastric
      mucosa, with particularly strong expression in the surface cells. IL-8 expression
      was also a feature of surface epithelium in the duodenal bulb, but was much
      reduced in the second part of the duodenum. In chronic H pylori-associated
      gastritis gastritis gastric epithelial IL-8 expression was increased and
      expression of IL-8 within the lamina propria was evident. By contrast, large
      areas of IL-8 negative epithelium were observed in the body mucosa of a subject
      with Menetrier's disease. In gastric carcinoma the tumour cells were positive for
      IL-8. IL-8 was also detected by immunofluorescence in unstimulated Kato 3 and MKN
      45 cells, and constitutive IL-8 gene expression in these cell lines was confirmed
      by detection of IL-8 mRNA by RT-PCR. CONCLUSIONS: Immunoreactive IL-8, a potent
      neutrophil chemotactic and activating factor, is present in the epithelium of
      both normal and inflamed gastric mucosa with increased expression in the latter.
      There is site dependent variation in epithelial IL-8 expression within the
      gastroduodenal mucosa. The expression of the pro-inflammatory cytokine IL-8 in
      gastric carcinoma cells may influence peritumoural cellular infiltrates.

PMID- 8132814
TI  - Comparison of Vitek and Cobas Micro systems with a semiautomated conventional
      microsystem for identification and susceptibility testing of gram negative
      bacilli.
AB  - AIMS: To compare the sensitivity and specificity of two semiautomated systems
      against a conventional (MIC 2000) test system for the identification and
      antibiotic susceptibility of Gram negative bacteria. METHODS: Clinical isolates
      of Gram negative bacilli (188 urinary and 229 non-urinary strains) were
      identified and tested for antibiotic susceptibility in the Cobas Micro and MIC
      2000 systems. Of these, 359 strains were then tested in the Vitek and MIC 2000
      systems. Two hundred and forty three strains were tested in all three systems
      immediately after isolation. Forty three were also tested only in the Vitek and
      MIC 2000 systems immediately after isolation. The remaining 174 strains were
      tested after storage at -20 degrees C for several months. RESULTS: The Cobas
      Micro and MIC 2000 systems agreed on the identification of 310 of the 417 (74.3%)
      strains; the Vitek and MIC 2000 systems agreed on 338 of the 359 (94.2%) strains.
      The Cobas Micro system correctly identified 86.8% of strains tested after storage
      and 65.4% of those immediately after isolation. Organism-antibiotic combinations
      (non-urinary isolates) were tested in the Cobas Micro and MIC 2000 systems (n =
      2335), in the Vitek and MIC 2000 systems (n = 999). Essential correlation
      (complete agreement plus minor errors) was observed in 98% (with 90% complete
      agreement) in the former and in 97% (with 86% complete agreement) in the latter.
      For the urinary isolates, 1949 organism-antibiotic combinations were analysed in
      the Cobas Micro and MIC 2000 systems where complete agreement was observed in 92%
      (with 3% very major discrepancies), for 1382 urinary organism-antibiotic
      combinations tested in the Vitek and MIC 2000 systems, the figures were 95% and
      2%, respectively. CONCLUSIONS: The Vitek system is highly accurate in the
      identification and antibiotic susceptibility testing of Gram negative bacteria.
      The Cobas Micro system has many shortcomings in its identification of Gram
      negative rods, especially freshly isolated strains, but it is comparable with the
      Vitek system in antibiotic susceptibility testing.

PMID- 8132815
TI  - Deriving a useful packed cell volume estimate from haemoglobin analysis.
AB  - A method is described whereby the packed cell volume (PCV) of a blood sample can
      be estimated from the haemoglobin concentration. The method defines the relation
      existing between haemoglobin concentration and the PCV of blood samples and uses
      the mathematical formula thus obtained to estimate an unknown PCV value for a
      sample by extrapolation from the known haemoglobin value of the same sample. The
      method could be used in large scale field studies where haematological services
      are not available and where an evaluation of red cell status of vitamins such as
      folate is required.

PMID- 8132816
TI  - Oncogenic hypophosphataemia and ectopic corticotrophin secretion due to oat cell
      carcinoma of the trachea.
AB  - A case of oat cell carcinoma causing Cushing's syndrome and oncogenic
      hypophosphataemic osteomalacia is reported. The association of the two disorders
      in one patient is believed to be unique and this is the second reported case of
      oncogenic osteomalacia caused by oat cell carcinoma.

PMID- 8132817
TI  - Mycetoma caused by Nocardia transvalensis.
AB  - Nocardia transvalensis can be a rare cause of actinomycotic mycetoma. A 40 year
      old man presented with his right arm showing multiple discharging sinuses, which
      had been present for four years. N transvalensis was isolated from a biopsy
      specimen. No other underlying disease was detected. The patient was successfully
      managed with surgical excision of the lesion and treatment with co-trimoxazole.
      This is the first case of N transvalensis infection to be reported from the
      Indian subcontinent as far as is known.

PMID- 8132818
TI  - Blood exchanged in ritual ceremonies as a possible route for infection with
      hepatitis C virus.
AB  - Of 52 blood donors (25 men and 27 women) counselled because their donation tested
      positive for hepatitis C virus antibody, seven (13.5%) gave a history of
      practising the ritual of blood exchange in their childhood or early adult life.
      This practice can cause transmission of blood borne infections or
      alloimmunisation, or both.

PMID- 8132819
TI  - Demonstration of oestrogen receptors in paraffin wax sections of breast carcinoma
      using the monoclonal antibody 1D5 and microwave oven processing.
AB  - This study aimed at assessing the usefulness of a new monoclonal antibody (1D5)
      for the demonstration of oestrogen receptors (ER) in paraffin wax sections, using
      brief microwave processing rather than proteolytic predigestion. Routinely
      processed paraffin wax sections of 50 cases of breast carcinoma with known ER
      concentrations, estimated by the standard dextran-coated charcoal (DCC)
      biochemical assay, were examined using the avidin-biotin complex-immunoperoxidase
      technique. The results were assessed semiquantitatively, using a five grade
      scoring system. Of the 50 cases examined, 37 were positive and six were negative
      by both DCC and immunohistology. Of the remaining seven cases, three (6%) were
      negative by DCC but positive with immunohistology, and four (8%) were positive
      with DCC and negative with immunohistology. The DCC results of the latter four
      cases were 10, 14, 14 and 16 fmol/mg protein which is at the lowest level of
      positivity, our cutoff point being less than 10 fmol. The monoclonal antibody
      1D5, as used in this study, can provide easily assessed reliable information
      about the ER status of breast carcinoma using routinely processed paraffin wax
      sections.

PMID- 8132820
TI  - Prevalence of Epstein-Barr virus in the cervix.
AB  - Cervical smears from 327 women were examined using the polymerase chain reaction
      (PCR) targeted to a sequence in the Bam H1 W region of the Epstein-Barr virus
      (EBV) to determine the prevalence of the virus in the cervix. EBV was detected in
      131 (40%) of the 327 women. Of the 235 women with normal cytology, 98 (42%) were
      positive. Of the 92 women with dyskariotic smears, 33 (36%) were positive.

PMID- 8132821
TI  - Use of low molecular weight heparin during pregnancy.

PMID- 8132822
TI  - Investigation and management of haemorrhagic disorders in pregnancy. Haemostasis
      and Thrombosis Task Force.

PMID- 8132823
TI  - Can Ki67 immunostaining predict response to radiotherapy in oral squamous cell
      carcinoma?
AB  - AIMS: To determine whether immunohistochemical evaluation of the abatement of
      proliferating cells after a first course of radiotherapy could predict the final
      response to treatment in oral squamous cell carcinoma (SCC). METHODS: Frozen
      sections from 31 cases of histologically confirmed oral SCC were stained with the
      monoclonal antibody Ki67 at diagnosis and after 10 Gy of radiotherapy. The
      percentage difference of Ki67 positive cells among the biopsy specimens taken at
      the beginning and after 10 Gy was correlated with the clinical response obtained
      at the end of the treatment and its significance determined. RESULTS: The
      percentage of Ki67 positive cells at diagnosis had no significant correlation
      with the final therapeutic result of radiotherapy. By contrast, the 32%
      difference of proliferating cells after 10 Gy of radiotherapy significantly
      differentiated responders from non-responders (p < 0.05). Furthermore, the
      abatement of the growth fraction after 10 Gy of radiotherapy was significantly
      correlated with the complete response (p < 0.01). CONCLUSIONS: These data show
      that the immunohistochemical evaluation of the abatement of Ki67 positive cells
      after 10 Gy of radiotherapy provides an independent variable of responsiveness to
      radiotherapy, allowing a reliable prediction of the final therapeutic result to
      be made.

PMID- 8132824
TI  - Distribution of the matrix metalloproteinases stromelysin, gelatinases A and B,
      and collagenase in Crohn's disease and normal intestine.
AB  - AIMS: To investigate the role of the matrix metalloproteinases (MMPs) in the
      connective tissue changes seen in the intestine in Crohn's disease. METHODS:
      Indirect immunofluorescence microscopy using specific antibodies to the MMPs
      (collagenase, gelatinase A and B, and stromelysin) were used to assess the
      distribution of these enzymes in normal and diseased intestine. RESULTS: In
      normal intestine the matrix metalloproteinases were confined to a few isolated
      inflammatory cells, but in Crohn's disease, the inflammatory infiltrate was
      associated with increased numbers of polymorphonuclear leucocytes which stained
      positive for gelatinase B. Stromelysin was also detected extracellularly on the
      connective tissue matrix in regions of smooth muscle cell proliferation and
      mucosal degradation. Interestingly, in ulcerative colitis, another inflammatory
      bowel disease, stromelysin was localised in the lamina propria in regions of
      mucosal loss. CONCLUSIONS: The increased numbers of inflammatory cells containing
      gelatinase B, and the localisation of extracellular stromelysin in regions of
      fibrosis and mucosal degradation, suggest that these enzymes have a role in the
      pathological changes seen in Crohn's disease. In cases of ulcerative colitis
      stromelysin was also detected on the lamina propria in regions of mucosal loss,
      and seems to be associated with the connective tissue changes that precede
      mucosal loss.

PMID- 8132825
TI  - Value of electron microscopy in diagnosis of renal disease.
AB  - AIMS: To assess the role and value of electron microscopy in the diagnosis of
      renal disease. METHODS: Retrospective evaluation of 88 renal biopsy specimens
      received for primary diagnosis by assessment of the contribution of electron
      microscopy to the final diagnosis in the knowledge of the light microscopy and
      immunofluorescence findings. RESULTS: Electron microscopy had an important
      diagnostic role in 75% of cases and was essential or necessary for diagnosis in
      25%. In 25% of cases electron microscopy was considered unhelpful in diagnosis.
      CONCLUSION: Electron microscopy has an integral role in the diagnosis of renal
      disease, and tissue should be taken for electron microscopy in all cases if
      possible. In some selected cases once the light microscopy and immunofluorescence
      findings are known it may be possible to forego electron microscopic examination.
      Electron microscopy is particularly useful in the differential diagnosis of
      minimal change disease and the nephrotic syndrome.

PMID- 8132826
TI  - Immunohistochemical study of vascular injury in acute multiple sclerosis.
AB  - AIMS: To examine the vascular changes occurring in three archival cases of acute
      multiple sclerosis, and to provide immunohistochemical evidence of early
      endothelial cell activation and vascular occlusion in this condition. METHODS:
      Central nervous system tissues from three cases of acute active multiple
      sclerosis and six non-inflammatory controls were stained using the following
      methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's
      silver, and reticulin. Tissues were also immunostained with specific antibodies
      against collagen type IV, factor XIIIa, class II antigens, glial fibrillary
      acidic protein, and fibrinogen. RESULTS: Early vascular endothelial cell
      activation which may progress to vasculitis and vascular occlusion including
      class II antigen expression and fibrin deposition were identified. The vascular
      changes were seen prior to cerebral parenchymal reaction and demyelination, and
      were not seen in control cerebral tissues. CONCLUSION: It is proposed that
      vascular endothelial cell activation may be an early and pivotal event in the
      evolution of multiple sclerosis, and that demyelination may have an ischaemic
      basis in this condition. The vascular endothelium may contain an early element in
      the evolution of multiple sclerosis.

PMID- 8132827
TI  - Simple method for comparing reliability of two serum tumour markers in breast
      carcinoma.
AB  - AIMS: To compare the two breast tumour markers, CA15-3 and mucinous-like
      carcinoma associated antigen (MCA), using Receiver Operating Characteristic (ROC)
      curve analysis. METHODS: One hundred and ninety six patients "presenting" with
      breast carcinoma had serum CA15-3 and MCA concentrations measured. RESULTS: Using
      these markers as indicators of stage IV disease at the recommended laboratory
      level, true positive rates (TPR) and false positive rates (FPR) were obtained as
      follows: CA15-3 TPR = 75%, FPR = 7.4%, MCA TPR = 80%, FPR = 59.1%. By increasing
      the CA15-3 cutoff level to 45 U/ml, a TPR and FPR of 75% and 0.6%, respectively
      were obtained. By increasing the MCA cutoff level to 23 U/ml, a TPR and FPR of
      65% and 2.3%, respectively, were obtained. CONCLUSIONS: Using ROC curve analysis
      shows that CA15-3 is a superior indicator of metastatic breast disease than MCA
      at recommended laboratory levels, and by altering the cutoff points, the
      specificity and sensitivity for both these markers can be improved.

PMID- 8132828
TI  - Cellular distribution of human leucocyte adhesion molecule ICAM-3.
AB  - AIMS: To describe the distribution of the recently cloned human leucocyte
      adhesion molecule ICAM-3 in normal and neoplastic tissues and cell lines.
      METHODS: A panel of four monoclonal antibodies to ICAM-3 were used to stain cell
      lines and sections of human lymphoid tissues using the alkaline phosphatase-anti
      alkaline phosphatase immunocytochemical method (APAAP). RESULTS: In peripheral
      blood ICAM-3 was detected on monocytes, granulocytes, and most lymphocytes. In
      sections of human lymphoid tissue the antigen was also found on most lymphocytes,
      but many of the proliferating B cells found in the germinal centres of secondary
      lymphoid follicles were ICAM-3 negative. ICAM-3 was also found on neoplastic
      white cells (in chronic lymphocytic leukaemia, hairy cell leukaemia, acute and
      chronic myeloid leukaemia, and multiple myeloma) with the exception of Reed
      Sternberg cells in Hodgkin's disease, many of which were negative. ICAM-3 was
      consistently absent from cells and tissues of non-haemopoietic origin.
      Endothelium (which expresses ICAM-1) was negative for ICAM-3, with the exception
      of vessels in some neoplastic lymphoid samples which showed variable staining for
      ICAM-3. CONCLUSIONS: These findings suggest that ICAM-3 is essentially restricted
      to the haemopoietic system and is reciprocal in its expression to ICAM-1, in that
      it is present on resting cells and its level falls as a result of cell
      activation.

PMID- 8132829
TI  - Stability of infectious HIV in clinical samples and isolation from small volumes
      of whole blood.
AB  - AIMS: To evaluate the stability of infectious HIV in clinical samples and the
      efficiency of isolating it from small volumes of whole blood. METHODS: Titres of
      infectious HIV were measured in peripheral blood mononuclear cells and plasma 2,
      24, and 48 hours after peripheral blood had been collected from 10 HIV positive
      adult volunteers. Volumes of whole blood (1 ml to 5 microliters), collected from
      a further five volunteers, were used to determine the minimum volume from which
      HIV could be isolated. Infectious HIV was isolated by co-culture with
      phytohaemagglutinin stimulated umbilical cord mononuclear cells. RESULTS:
      Geometric mean titres of infectious HIV seemed to be more stable in peripheral
      blood mononuclear cells than in plasma. HIV was recovered from all 10 peripheral
      blood mononuclear cell samples during the 48 hours after sample collection, but
      from only four plasma samples. HIV could occasionally be isolated from 5
      microliters of whole blood and reliably from 200 microliters. CONCLUSIONS: HIV
      can be isolated from peripheral blood mononuclear cells and plasma for up to 48
      hours after sample collection. Isolation of HIV from small volumes of whole blood
      has applications for the diagnosis and management, of HIV positive children.

PMID- 8132830
TI  - Complement activation by cellulosic dialysis membranes.
AB  - AIMS: To assess the effect of cellulosic dialysis membranes on the production of
      complement degradation products to determine to the role of the classical
      pathway. METHOD: Complement activation was studied in 33 patients during a single
      haemodialysis session using cellulosic membranes. Pre- and post-dialysis plasma
      EDTA valves of C3, C4, C3dg, C4d and C reactive protein (CRP) were measured.
      Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Post
      dialysis C4 (p = 0.0003), C3dg (p < 0.0001), and C4d (p = 0.003) concentrations
      were increased compared with pre-dialysis values. There was no significant change
      in C3 (p = 0.095) and CRP (p = 0.13) values. Post-dialysis C3dg and C4d
      concentrations correlated significantly (p = 0.007). IgG, an undialysed molecule,
      was quantified and post-dialysis valves were significantly higher than those
      before dialysis (p = 0.0002), indicating a degree of haemoconcentration. To
      remove this effect, the C3:IgG, C4:IgG, C3dg:IgG, C4d:IgG and CRP:IgG ratios were
      calculated. Compared with pre-dialysis values, post-dialysis C3dg:IgG and C4d:IgG
      ratios were increased and C3:IgG decreased significantly. No change was observed
      in C4:IgG and CRP:IgG ratios. CONCLUSION: This study confirms that significant
      complement activation takes place following dialysis with cellulosic membranes.
      This is denoted by an increase in C3dg. This was paralleled by a rise in C4d,
      implying a contributory role for the classical pathway. Concomitant post-dialysis
      increases in IgG and C4 indicate a degree of haemoconcentration; but removal of
      this effect shows that C3dg and C4d are increased following dialysis--suggesting
      classical, in addition to alternative, pathway activation.

PMID- 8132831
TI  - Increase in mean platelet volume in patients with chronic renal failure treated
      with erythropoietin.
AB  - AIMS: To assess whether r-HuEPO (recombinant human erythropoietin) has any effect
      on thrombopoiesis in patients with chronic renal failure. METHODS: This was a
      retrospective study of 78 patients with chronic renal failure undergoing either
      haemodialysis (n = 57) or intraperitoneal dialysis (n = 21). All patients had a
      full blood count (in EDTA) measured before starting r-HuEPO and at monthly
      intervals thereafter up to six months. Variables studied were haematocrit,
      platelet count, mean platelet volume (MPV) and platelet distribution width (PDW).
      Other groups of control patients were also studied--patients with chronic renal
      failure receiving dialysis but not r-HuEPO (n = 40) and a group of patients with
      normal renal function who were receiving aspirin (n = 30). RESULTS: There was a
      significant increase in mean haematocrit (p < 0.01) and in mean platelet volume
      (p < 0.001) over the six month period, but no change in either total platelet
      count or platelet distribution width in the patients with chronic renal failure
      receiving r-HuEPO. In contrast, both the control groups showed no significant
      change in MPV. CONCLUSIONS: The results suggest that r-HuEPO affects
      thrombopoiesis and may be part of a group of humoral factors contributing to
      megakaryocyte development and maturation. Larger platelets are more reactive and
      may contribute to the increased risk of thrombosis associated with r-HuEPO.

PMID- 8132833
TI  - Gastrointestinal tract aspergilloma: possible cause of malabsorption.
AB  - A 62 year old man with chronic lymphocytic leukaemia presented with
      malabsorption, the cause of which could not be found during life. Necropsy
      examination showed aspergillosis, limited to the stomach, where tumour-like
      masses were seen, the oesophagus, and lungs. This case illustrates the problems
      of diagnosing fungal infections in life and the importance of clinicopathological
      correlation at necropsy.

PMID- 8132832
TI  - Acquired pseudo-pseudo Bernard-Soulier syndrome complicating Gaucher's disease.
AB  - AIMS: To investigate the abnormality in platelet function in two patients with
      type I Gaucher's disease causing a chronic bleeding tendency despite
      normalisation of the platelet count after spleen removal. METHODS: Routine
      laboratory methods were used to assess baseline coagulation. Platelet
      aggregometry was used to assess platelet responses to a range of agonists, and
      abnormalities were further assessed in mixing experiments using washed platelets
      and patients' plasma. RESULTS: Platelets from both patients with Gaucher's
      disease failed to agglutinate to ristocetin, despite normal platelet surface
      glycoprotein (GP) Ib and plasma von Willebrand factor activity. The agglutination
      of normal washed platelets was abolished by incubation in patient plasma. The
      inhibitory activity did not lie in the IgG fraction of patient plasma, and was
      found to be loosely associated with the patient platelet surface. CONCLUSIONS:
      The inhibition of ristocetin induced platelet agglutination in patients with
      Gaucher's disease causes a prolonged skin bleeding time. This could be due to the
      accumulated glucocerebroside in the plasma coating the platelet membrane. It is
      suggested that the term pseudo-pseudo Bernard-Soulier syndrome would be
      appropriate, as on initial screening, the abnormality has the features of Bernard
      Soulier syndrome, but further investigation shows normal plasma von Willebrand
      activity and platelet surface GP Ib concentrations. The inhibitory activity is
      not due to a platelet specific antibody as is the case in pseudo-Bernard Soulier
      syndrome.

PMID- 8132834
TI  - Morphological transformation of Helicobacter pylori during prolonged incubation:
      association with decreased acid resistance.
AB  - The survival of clinical isolates of H pylori at two cultural ages (two and four
      days) at pH 2, in the presence of different buffers, with and without urea, was
      investigated. It was found that the morphological changes which occur with longer
      incubation of H pylori have an inverse correlation with its resistance to an
      acidic environment. The finding that the addition of urea almost reversed this
      phenomenon and prolonged survival of the cultures emphasises the role of urea in
      the survival of H pylori in acidic environments.

PMID- 8132835
TI  - Bacteraemia caused by Campylobacter spp.
AB  - The genus Campylobacter has become increasingly recognised as the cause of
      various infections. Campylobacter jejuni and C coli cause acute gastroenteritis
      in man all over the world. C jejuni enteritis can lead to bacteraemia, but its
      actual incidence remains unknown. Seven cases of bacteraemia caused by C jejuni
      or C coli are reported, from the blood of seven patients: five immune deficient
      adults; a newborn baby; and a patient who had had abdominal surgery. Patients who
      develop diarrhoea as a result of Campylobacter infection are at risk of
      bacteraemia thereafter.

PMID- 8132836
TI  - Comparison of immunoturbidimetric and Lowry methods for measuring concentration
      of very low density lipoprotein apolipoprotein B-100 in plasma.
AB  - To assess whether the Lowry-tetramethylurea method for measuring apolipoprotein B
      100 (apo-B) in very low density lipoprotein (VLDL) could be replaced by direct
      assay of VLDL apo-B using a highly practicable immunological method. Seventy five
      fasting blood samples were collected from patients attending the lipid clinic at
      this hospital. Plasma was separated immediately and VLDL isolated by preparative
      ultracentrifugation at solution density 0.93-1.006 kg/l. Apo-B was precipitated
      from an aliquot of the VLDL fraction using the tetramethylurea (TMU) technique
      and protein mass determined by the Lowry method (LM); mean apo-B 83.02
      micrograms/ml (SD 74.85). Apo-B was also measured in VLDL using direct
      immunoturbidimetry on the Cobas-Fara analyser; mean apo-B 82.32 micrograms/ml (SD
      72.88). There was a very close correlation between methods (immunoturbidimetry =
      0.94.LM + 3.95, r = 0.97, p < 0.001). The mean difference between methods
      (constant error) was small (0.70 microgram/ml) and not significant (p = 0.742).
      Random error was 13.01 micrograms/ml by analysis of variance. It is concluded
      that immunoturbidimetry, a more rapid and convenient test, may replace the LM and
      TMU techniques for measuring VLDL apo-B concentration and that this method could
      be applied to research studies requiring analysis of large numbers of samples.

PMID- 8132837
TI  - AIDS presenting as focal segmental membranous glomerulopathy.
AB  - The case of a young, heterosexual man who was investigated for proteinuria is
      reported. A renal biopsy specimen showed a focal and segmental membranous
      glomerulopathy. He was later found to be HIV positive and died from cerebral
      infarction associated with HIV vasculitis 16 months after his initial
      presentation. Unusual forms of immune complex mediated glomerulopathies should
      alert the pathologist to the possibility of HIV associated disease.

PMID- 8132838
TI  - Spuriously high free thyroxine with the Amerlite MAB FT4 assay.
AB  - In the Amerlite MAB FT4 assay, as stated by the manufacturer, FT4 values should
      be normal in patients with anti-thyroid hormone autoantibodies. The case of a 69
      year old woman with a spuriously high FT4 using the Amerlite MAB FT4 assay is
      reported. Laboratory investigations showed that her spurious FT4 result was
      likely to have been caused by anti-thyroid hormone autoantibodies.

PMID- 8132839
TI  - Angiocentric invasion by lentigo maligna melanoma.
AB  - A case of angiocentric invasion by a lentigo maligna melanoma is reported.
      Pericapillary cuffing and permeative intimal expansion of veins by melanoma
      without luminal tumour cell emboli, thrombosis, or vascular destruction were
      associated with a lentigo maligna melanoma on the face of a 93 year old woman.
      This unusual infiltrative pattern suggests a specific interaction between
      melanoma cells and perivascular connective tissue elements, and may imply
      expression by tumour cells of receptors for molecules in the intima of blood
      vessels and in pericapillary stroma.

PMID- 8132840
TI  - Signet-ring cell lymphoma of bone marrow.
AB  - A case of signet-ring cell lymphoma affecting bone marrow is reported. The tumour
      presented as multiple lytic lesions in the lumbosacral spine. A bone biopsy
      specimen showed the typical appearances of signet-ring cell lymphoma, and the
      cells stained positively with antiserum to CD20, though neither immunoglobulin
      light or heavy chains could be shown within the vacuoles. The patient
      subsequently responded to chemotherapy.

PMID- 8132841
TI  - Benign familial hyperphosphatasaemia.

PMID- 8132842
TI  - Negative cytology preceding cervical cancer: causes and prevention.

PMID- 8132843
TI  - Cytotoxic activity of Helicobacter pylori enhanced by acetohydroxamic acid.

PMID- 8132844
TI  - Alternative method for transporting and storing gastric biopsy cultures of
      Helicobacter pylori.

PMID- 8132845
TI  - Clinical usefulness of detecting growth of Mycobacterium tuberculosis in positive
      Bactec phials using PCR.

PMID- 8132846
TI  - Medical microbiology, infectious diseases, and the public health: a trio in
      search of harmony.

PMID- 8132847
TI  - Treatment of human immunodeficiency virus infection and its associated
      complications in children.
AB  - Providing care to human immunodeficiency virus (HIV)-infected children requires a
      comprehensive, multidisciplinary approach. This review will address the current
      status of supportive care, treatment of HIV-associated complications and specific
      antiretroviral therapy. HIV affects multiple locations in the body resulting in a
      myriad of possible complications. These include opportunistic infections and
      malignancies secondary to immunodeficiency and central nervous system or other
      specific organ-related disease secondary to direct HIV involvement. Recent
      scientific advances have markedly enhanced the quantity and quality of life of
      HIV-infected children. Prophylaxis of Pneumocystis carinii pneumonia is the
      single most important therapeutic advance for the HIV-infected patient. Other
      advances for the treatment and prevention of HIV-related infections should
      similarly improve survival and reduce hospital stays. Antiretroviral therapy is
      relatively new. The currently available nucleoside reverse transcriptase
      inhibitors have proven efficacy. The role of single agents or combinations is
      being established. However, this group of antivirals has limitations that make
      alternate approaches essential. Augmentation of the patient's immune response
      will likely be a key to any future successful treatment regimen.

PMID- 8132848
TI  - New antithrombotic strategies for resistant thrombotic processes.
AB  - Life-threatening thrombo-occlusive events producing heart attacks and strokes
      develop in patients at sites of atherosclerotic arterial stenoses when plaques
      rupture, a process resistant to both aspirin and heparin. Resistant thrombotic
      complications are also troublesome during therapeutic thrombolytic or mechanical
      interventions for symptomatic atherosclerotic vascular disease, including
      angioplasty, various types of atherectomies, endarterectomy, endovascular stent
      deployment, or implanted small caliber vascular grafts. In this review
      therapeutic strategies for more effective management of these resistant, platelet
      dependent, occlusive thrombi are discussed, including: a) inhibition of platelet
      recruitment by anti-GPIIb/IIIa monoclonal antibodies, naturally occurring
      peptides containing RGD sequences, or synthetic competitive analogs; b) direct
      inactivation of thrombin bound to thrombus by natural or synthetic antithrombin
      peptides; c) interruption of thrombin's production by natural or synthetic
      antagonists of Factor Xa or extrinsic and intrinsic coagulation pathways; and d)
      elimination of thrombogenicity at sites of vascular injury by immediately
      restoring confluent endothelium or prior therapy with dietary n-3 fatty acids.
      However, antagonists of both GPIIb/IIIa- and thrombin-dependent platelet
      recruitment produce equivalent inhibition of thrombus formation and platelet
      hemostatic function. Interestingly, hemostasis is spared by therapies that
      inhibit thrombin's production. Recommendations for development strategies are
      related to the relative hemostatic risks and antithrombotic benefits.

PMID- 8132849
TI  - Comparison of the pharmacokinetics of naproxen tablets and suspension in
      children.
AB  - Twenty-three children, aged 8 to 14 years, with postoperative pain, were randomly
      assigned to receive a fixed 250-mg dose (4.66-7.58 mg/kg) of naproxen as either a
      liquid suspension or tablet. After an overnight fast, the serum concentrations
      were measured before and at 0.5, 1, 2, 3, 4, 8, 12, 18, and 24 hours after
      administration of naproxen. The concentration versus time data were best fit to a
      one-compartment open model. The area under the concentration versus time curve,
      apparent volume of distribution (VDss/F), and elimination parameters (CL/F, Ke,
      elimination half-life) were similar in children who received suspension or
      tablets. Although the apparent maximum peak plasma concentration (Cmax) was
      greater in children who received tablets compared with those who received the
      suspension, Cmax/area under the curve (AUC), apparent time to maximum peak
      concentration (tmax), Ka, and estimated time to 10%, 50%, and 90% absorption
      (T10, T50, T90) were not different. The dose range was relatively narrow; hence,
      direct relationships between dose and elimination parameters, VDss/F, apparent
      tmax, Ka, T10, T50 or T90 were not observed. Neither VDss/F or CL/F were age
      related over the relatively narrow range of ages that were studied. Elimination
      of naproxen in our patients was more rapid than has previously been reported in
      children or adults, however. From a practical standpoint, naproxen tablets and
      suspension seem to be bioequivalent in fasting children ages 8 to 14 years.

PMID- 8132850
TI  - Pharmacokinetic and pharmacodynamic profiles of CS-518, a selective, long-lasting
      thromboxane synthase inhibitor, after single and multiple oral administration to
      healthy volunteers.
AB  - A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered
      to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic
      properties were investigated. The time profile of drug concentrations in plasma
      was determined, and the effects of the drug on platelet aggregation in plasma
      induced by arachidonic acid (AA) and adenosine diphosphate (ADP) ex vivo were
      examined. The production of TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1
      alpha) in serum during whole blood coagulation ex vivo also were examined. In the
      single-dose study (50, 100, and 200 mg), plasma concentrations of the drug were
      well fitted to a one-compartment open model with first-order absorption. The area
      under plasma concentration curve (AUC) and maximum plasma concentration (Cmax)
      showed dose-related increases, whereas the mean elimination half-lives remained
      rather constant (.68-.92 hour). The drug was recovered in urine by 32 to 37% and
      62 to 65% as unchanged and conjugated forms (acylglucuronide), respectively,
      showing almost complete absorption of CS-518. The effect of food intake on the
      pharmacokinetics of CS-518 was determined at the dose of 100 mg. The time to
      reach Cmax was prolonged from .42 to 2.08 hours and the Cmax was decreased by
      about 66%, whereas the AUC and urinary recovery showed no significant changes.
      The platelet aggregation in plasma induced by AA was markedly inhibited, whereas
      the secondary aggregation induced by ADP was inhibited to a much less degree.
      Platelet aggregation by AA was almost completely inhibited 2 hours after
      administration of any dose and the duration for maintaining the significant
      inhibition tended to depend on the dose ranging from 48 to 72 hours after
      administration, which was much longer than expected from the plasma concentration
      of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132851
TI  - Verapamil and nifedipine in combination for the treatment of hypertension.
AB  - The authors examined the efficacy and safety of the combination of verapamil and
      nifedipine in the control of hypertension. Retrospective analysis of blood
      pressures was obtained on 50 patients who had historically documented essential
      hypertension and were receiving verapamil and nifedipine. The patients had
      moderate to severe hypertension; 27 of 50 (54%) were uncontrolled on prescribed
      regimens of two or more separate classes of drugs. Control was defined by the
      ability to maintain a blood pressure of < or = 160/90 by providing doses of
      verapamil (max: 480 mg/day) and nifedipine (max: 180 mg/day). Twenty-nine (58%)
      were black and 21 (42%) were white. Ages ranged from 16 to 84 years. Mean
      duration of therapy was 1-2 years. Only 3 of 50 (6%) were control failures after
      providing verapamil and nifedipine. Three of 50 (6%) were discontinued because of
      side effects--reversible hepatitis (2) and rash (1). There were no serious
      adverse events, i.e., CHF or arrhythmias. Manageable ankle edema was seen in 14
      of 50 (28%) patients. Verapamil and nifedipine, a combination of a
      dihydropyridine and a non-dihydropyridine calcium antagonist, was effective and
      safe in this group of patients with difficult-to-manage hypertension.

PMID- 8132852
TI  - Plasma and leukemic cell pharmacokinetics of high-dose N4-behenoyl-1-beta-D
      arabinofuranosylcytosine in acute leukemia patients.
AB  - The pharmacokinetics of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), a
      lipophilic antitumor analog of 1-beta-D-arabinofuranosylcytosine (ara-C), was
      investigated, by assay of plasma and leukemic cells of ten acute leukemic
      patients receiving 60-minute intravenous (IV) infusion of 700 mg/m2 BHAC, for
      BHAC and 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) by high
      performance liquid chromatography, ara-C by radioimmunoassay, and 1-beta-D
      arabinofuranosyluracil (ara-U) by gas chromatography-mass fragmentography. The
      plasma concentration of BHAC reached a maximum (173.4 +/- 75.3 micrograms/mL) at
      the end of the infusion and then declined in a biphasic pattern with an initial
      phase half-life (t1/2 alpha) of 1.00 +/- .36 hours and a second-phase half-life
      (t1/2 beta) of 4.28 +/- 2.35 hours. That of ara-C similarly reached a maximum
      (102.2 +/- 39.9 mg/mL) at the end of the infusion and then declined with t1/2
      alpha of 1.37 +/- 1.11 hours and t1/2 beta of 11.2 +/- 4.31 hours. Intracellular
      ara-CTP concentration increased in a linear-accumulation manner for the first 4
      hours after the infusion, reached a maximum of .081 +/- .112 micrograms/10(7)
      cells at approximately 7 hours, and then declined very slowly in accordance with
      a one-compartment model with t1/2 of 13.56 +/- 9.62 hours.

PMID- 8132853
TI  - Pharmacokinetics of orally and intravenously administered cyclosporine in pre
      kidney transplant patients.
AB  - The pharmacokinetics of cyclosporine (CSA) and four metabolites were evaluated in
      eight hemodialysis subjects awaiting renal transplantation to compare metabolic
      patterns with those observed in post-transplant patients and normal volunteers.
      Each subject received a single 4-mg/kg intravenous and a single 10-mg/kg oral
      dose separated by a 1-week washout period. Blood samples were collected before
      and at .5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, and 24 hours after CSA dosing.
      Cyclosporine blood, plasma, and metabolite (M17, M1, M18, M21) levels were
      determined by high-pressure liquid chromatography. Mean (+/- standard deviation)
      CSA blood clearance was .47 +/- .15 L/hour/kg, steady-state volume of
      distribution (Vss) was 1.9 +/- .5 L/kg, and mean residence time (MRT) was 4.4 +/-
      1.8 hours after intravenous dosing. With plasma, mean clearance was .70 +/- .31
      L/hour/kg, Vss was 2.4 +/- 1.2 L/kg, and MRT was 3.7 +/- 2.2 hours. Cyclosporine
      bioavailability (F) averaged 24 +/- 11 and 24 +/- 15%, using blood and plasma,
      respectively. Values for clearance and Vss were approximately 30 to 100% greater
      than comparable estimates in healthy volunteers, but F and MRT were not altered
      to this extent. These changes might be explained on the basis of decreased
      protein binding in uremic patients. The area under the curve ratio for M17 and M1
      to CSA increased an average of 1.7- and 3.9-fold, respectively, after oral dosing
      compared with intravenous administration, indicating increased conversion during
      first-pass metabolism.

PMID- 8132854
TI  - Organization and functioning of an adverse drug reaction clinic.

PMID- 8132855
TI  - Hypoglycemia caused by selegiline, an antiparkinsonian drug: can such side
      effects be predicted?
AB  - Treatment with selegiline produced profound hypoglycemia in a 70-year-old man
      with Parkinson's disease. The hypoglycemia was accompanied by hyperinsulinemia
      and persisted for 1 week after selegiline was discontinued. Although this side
      effect of antidepressant monoamine oxidase inhibitors was well documented in 1959
      1968 publications, it was not known to the manufacturer of selegiline. Effects of
      drugs on glucose metabolism may be predictable through a novel molecular modeling
      technique developed in our laboratories, which shows that glucose exhibits
      stereochemical complementarity to a specific site in partially unwound DNA.
      Selegiline and other molecules affecting glucose metabolism fit into the same DNA
      base sequence. It therefore should be possible to employ this technique to
      identify pharmaceutical agents that possess hypoglycemic or hyperglycemic effects
      in vivo.

PMID- 8132856
TI  - Investigation of the influence of acetylsalicylic acid on the steady state of
      long-term therapy with theophylline in elderly male patients with normal renal
      function.
AB  - The risk inherent in the clinical control of patients with theophylline is widely
      recognized. Elderly patients may present an additional risk because of altered
      pharmacokinetics and the use of concomitant medication. Acetylsalicylic acid has
      been proposed for primary and secondary prevention of myocardial infarction and
      possible strokes. This investigation was undertaken to determine if concomitant
      administration of acetylsalicylic acid in elderly patients would alter steady
      state levels of theophylline. A population of smoking male patients older than 60
      years of age under long-term control of chronic obstructive pulmonary disease
      (COPD) with theophylline were evaluated for a baseline period of 3 days. Serum
      levels were measured at 6:00 AM and 6:00 PM. An enteric-coated acetylsalicylic
      acid preparation, 650 mg by mouth, was added to the daily slow-release
      theophylline, 6:00 AM hour dose regimen for 4 weeks. The serum levels of
      theophylline and salicylates were measured at 6:00 PM after dosing and at 6:00 AM
      the following day, at weekly intervals for 4 weeks. Urine specimens collected
      before administration of medication at 6:00 AM were analyzed for salicylates to
      further confirm dosage compliance. All volunteers continued to be clinically
      controlled throughout the treatment period and no symptoms of either overdose or
      underdose of either medication occurred. Plateau or trough theophylline serum
      levels did not change significantly during the salicylate treatment period.
      Salicylate serum levels did show during treatment self-induced metabolism. It is
      concluded that in elderly male patients, a daily concomitant therapeutic
      salicylate regimen does not alter steady-state serum theophylline levels and
      therefore does not per se necessitate the assay of theophylline blood levels in
      elderly patients.

PMID- 8132857
TI  - Dopamine-induced antihypertensive effects and plasma insulin rise are blocked by
      metoclopramide in labetalol-treated patients.
AB  - Eleven patients with moderate to severe hypertension were studied at the Vargas
      Hospital of Caracas. The patients were pretreated with labetalol, 800 to 1200
      mg/day, orally, over a period of 1 week, after which an intravenous infusion of
      dopamine, .5 to 3 micrograms/kg/minute, was given. Two intravenous dopamine
      infusions (30 minutes each) were performed before and after the injection of
      metoclopramide (30 mg, intravenous bolus). Two washout periods were also included
      before and after metoclopramide administration. Dopamine induced a decrease of
      blood pressure from 171.9 + 6.35/103.6 +/- 3.12 to 152.7 +/- 7.55/93.8 +/- 2.97
      mm Hg (P < .001) without altering heart rate, and it increased plasma insulin
      levels from 8.29 +/- .70 microU/mL to 12.09 +/- 1.83 microU/mL (P < .01).
      Metoclopramide caused no changes of blood pressure or plasma insulin levels.
      Hypotensive responses and plasma insulin increases due to dopamine were blocked
      by metoclopramide, however. The authors conclude that a dopaminergic receptor may
      be involved in some cardiovascular responses and in modulating insulin secretion
      in humans.

PMID- 8132858
TI  - Distribution and neurochemical phenotypes of caudal medullary neurons activated
      to express cFos following peripheral administration of cholecystokinin.
AB  - Immunocytochemical localization of the protein product of the proto-oncogene c
      fos allows anatomical identification of physiologically activated neurons. The
      present study examined the subnuclear distribution of cFos protein in the rat
      caudal medulla following peripheral administration of cholecystokinin
      octapeptide, which reduces feeding and gastric motility by a vagally mediated
      mechanism. To begin phenotypic characterization of neurons activated to express
      cFos following cholecystokinin treatment, double-labeling techniques were used to
      identify vagal motor neurons and neurons immunoreactive for tyrosine hydroxylase,
      neuropeptide Y, and neurotensin. Activated cells were most prevalent in the
      subnucleus medialis of the nucleus of the solitary tract, less prevalent in the
      subnucleus commissuralis, and virtually absent in the subnuclei centralis and
      gelatinosus. Many activated cells occupied the caudal area postrema; some of
      these were catecholaminergic. In contrast, activated cells were sparse within the
      medial rostral area postrema. Other activated cells occupied the dorso- and
      ventrolateral medulla and the midline raphe nuclei. Retrograde labeling of vagal
      motor neurons confirmed that very few were activated. Those that were activated
      occupied the caudal dorsal motor nucleus. In the dorsomedial medulla, 51% of
      catecholaminergic neurons and 39% of neurons positive for neuropeptide Y were
      activated, but no neurotensin-positive neurons were activated. In the
      ventrolateral medulla, 25% of catecholaminergic neurons and 27% of neuropeptide Y
      positive neurons were activated. By characterizing the subnuclear distribution
      and chemical phenotypes of neurons activated by exogenous cholecystokinin, these
      data contribute to elucidation of the neural circuits mediating the behavioral,
      physiological, and neuroendocrine effects produced by this peptide.

PMID- 8132859
TI  - Nucleus of the solitary tract and dorsal motor nucleus of the vagus nerve of the
      pigeon: localization of peptide and 5-hydroxytryptamine immunoreactive fibers.
AB  - The distribution of peptide and serotonin fibers in the nucleus of the solitary
      tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) in the pigeon
      (Columba livia) was investigated immunocytochemically. This information was
      correlated with the viscerotopic organization of the nuclei and with central NTS
      circuitry to suggest the role of the neurochemical containing fibers in the
      regulation of organ function. The distribution of fibers containing
      cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), enkephalin (ENK),
      neuropeptide Y (NPY), neurotensin (NT), substance P (SP), somatostatin (SS),
      vasoactive intestinal peptide (VIP), and 5-hydroxytryptamine (5-HT) was
      determined. Each substance had a distinct distribution within the subnuclei of
      NTS-DMNX, but certain generalities can be deduced. In the DMNX, fibers
      immunoreactive for ENK, NT, and SP were found in greatest concentration, while
      CGRP and 5-HT immunoreactive fibers were the least dense. This suggests that ENK,
      NT, and SP may have a significant modulatory effect on gastrointestinal
      functions. In the NTS overall, ENK, NT, SP, and VIP fibers were found in high
      density, CCK, NPY, SS, and 5-HT fibers were found in moderate density, and CGRP
      fibers were found in low density. However, some individual NTS subnuclei were
      found to contain moderate to high concentrations of each of the substances,
      including CGRP. Fibers containing CCK, ENK, NT, SP, SS, and VIP in the medial
      dorsal NTS subnuclei may regulate gastroesophageal functions. The caudal part of
      subnucleus lateralis parasolitarius did not contain most of the substances, which
      suggests that pulmonary function is not modulated by these neurochemicals. The
      boundaries of a subnucleus could sometimes be demarcated by a change in density
      of immunoreactive fibers between adjacent subnuclei. This was particularly
      evident in NTS subnuclei medialis dorsalis anterior centralis and lateralis
      parasolitarius, and in DMNX subnucleus posterior dorsalis magnocellularis. The
      selective distribution of peptide and serotonin immunoreactive fibers in various
      subnuclei of NTS-DMNX suggests that these substances may be differentially
      involved in neural circuits that mediate cardiovascular and gastrointestinal
      functions.

PMID- 8132860
TI  - Organization of the cerebral ganglion of the colonial ascidian Polyandrocarpa
      misakiensis.
AB  - The cerebral ganglion of a budding styelid ascidian, Polyandrocarpa misakiensis,
      whose phylogenetic location is midway between vertebrates and invertebrates, was
      studied by light and electron microscopy to obtain some insight into the
      evolution of the central nervous system. The lateral and ventral sides of the
      ganglion are surrounded by blood sinuses. The ganglion is covered with a thin
      fibrous sheath through which many nerve fibers run. The ganglion is composed of a
      cellular cortex and a fibrous medulla. The cortex consists of three to six layers
      of large and small neurons. Some neurons are also scattered within the medulla.
      Many neurons are monopolar, and some are bi- or multipolar. The cytoplasm of the
      large neurons is dense with extensive rough endoplasmic reticulum, free
      ribosomes, mitochondria, one or more Golgi complexes, large dense bodies, and
      many clear or dense vesicular structures. Some neurons send their processes
      directly into the lumen of the sinuses. The medulla is composed of loosely
      arranged nerve fibers without cellular wrappings. The medullary fibers contain
      vesicles and granules of various sizes, and microtubules. At the anterior and
      posterior ends of the ganglion, the medullary fibers are assembled into thick
      peripheral nerve fiber bundles. The peripheral nerve fibers are enveloped and
      subdivided by fibrous structures. Synapses are found in the medulla, in the
      cortex, and between the peripheral nerve fibers. The presence of neurons and
      axodendritic or axoaxonic synapses in the peripheral nerve fibers is consistent
      with a diffuse organization of the central nervous system of the ascidians. The
      morphology of the central nervous system synapses is comparable to that of other
      invertebrates, but the locations of the synapses are similar to those of
      vertebrates.

PMID- 8132861
TI  - Modulation of low-affinity nerve growth factor receptor in injured adult rat
      spinal cord motoneurons.
AB  - Spinal and brainstem motoneurons of the adult rat reexpress low-affinity nerve
      growth factor receptor (LNGFR) and its mRNA after axotomy. We have previously
      reported the time courses of this reexpression after cut (no regeneration) or
      crush (followed by regeneration) of the sciatic nerve. We have shown that the
      length of the different phases of this reexpression (appearance, maintenance and
      disappearance) can vary according to the type of axotomy. With the present study
      we expand our previous data and describe and analyze the modulation the LNGFR
      expression in adult spinal cord motoneurons following different lesion paradigms.
      In one approach we have imposed three traumatic injuries that still allow
      regeneration of the sciatic nerve but with a different time course with respect
      to the crush injury (application of a silicone regeneration chamber, multiple
      crushes and delayed repair of ligated nerves). In a second approach, we have
      determined the capability of three toxic or metabolic injuries to induce LNGFR
      expression without any direct trauma of the nerve (experimental diabetogenesis,
      botulinum and alpha-bungarotoxin intoxication and 2,5-hexanedione intoxication).
      In a third approach, we have investigated the effect of the block of the
      axoplasmic transport on the LNGFR expression following different topical
      applications of vincristine combined with a nerve crush. The results we present
      are consistent with the idea that: (1) LNGFR immunoreactivity in adult
      motoneurons is expressed by motoneurons that are attending to an axonal outgrowth
      and not a generic signal of cellular damage or impairment of the motor function;
      (2) LNGFR expression in these motoneurons is related to and parallels the
      outgrowth process time frame, and (3) the signal/s that trigger and sustain this
      reexpression may be retrogradely transported from the periphery.

PMID- 8132862
TI  - Development of the thalamic reticular and perireticular nuclei in rats and their
      relationship to the course of growing corticofugal and corticopetal axons.
AB  - This study examines the connections of the thalamic reticular and perireticular
      nuclei during development. In addition, because these nuclei lie directly in the
      path of corticofugal and corticopetal axons during development, we have examined
      the relationship of these growing axons to the reticular and perireticular cell
      groups. Neurones were labelled by applying DiI, wheat germ agglutinin conjugated
      to horseradish peroxidase (WGA-HRP), or HRP to the dorsal thalamus and/or
      cerebral cortex of rats at different stages of development. The axons of neurons
      in the reticular nucleus reach the dorsal thalamus as early as embryonic day (E)
      14. At this age, and during later prenatal development, a small DiI implant
      limited to the presumptive lateral geniculate nucleus labels reticulothalamic and
      thalamocortical axons which travel in a clearly defined bundle through the
      thalamus. During late gestation, thalamocortical (approximately E15) and
      corticothalamic (approximately E17) axons pass directly through the reticular
      nucleus toward their targets. It is not until birth that collaterals are seen
      extending into the nucleus from the parent axons. Neurones in the perireticular
      nucleus, in contrast to those in the reticular nucleus, are not labelled from the
      lateral geniculate nucleus until after birth. The perireticular nucleus is very
      large at a stage when the first thalamocortical axons leave and when the first
      corticothalamic axons approach the thalamus. These axons are seen to change
      course sharply in the region of the internal capsule, where there are many
      perireticular cells. Corticothalamic axons turn toward the reticular nucleus, and
      thalamocortical axons turn toward the cortical subplate. Corticospinal and
      corticobulbar axons, on the other hand, pass directly through the perireticular
      region toward their more caudal targets. After these axons have reached their
      targets, the perireticular nucleus reduces dramatically in size.

PMID- 8132863
TI  - GABAergic innervation of the Mauthner cell and other reticulospinal neurons in
      the goldfish.
AB  - The Mauthner cells are pair of identifiable hindbrain neurons that participate in
      the escape response of fishes. Membrane excitability in these cells is regulated
      by inhibitory neurons that use glycine as a transmitter. We examined the
      possibility that the inhibitory transmitter gamma-amino butyric acid (GABA) may
      also act on the Mauthner cells. We used immunocytochemical methods involving an
      antibody against glutamic acid decarboxylase (GAD), the synthesizing enzyme for
      GABA. Our study revealed dense GAD immunoreactive terminals surrounding the
      Mauthner cells. Puncta counts showed that the distribution of GAD
      immunoreactivity was densest at the distal lateral dendrite of the Mauthner
      cells; the distribution of puncta tapers gradually in regions closer to the soma.
      The axon cap was devoid of GABAergic immunoreactivity. We also performed
      unilateral lesions of the octaval nuclei to evaluate the origin of the GAD
      immunoreactive terminals. Following the lesions, we found marked decreases in GAD
      immunoreactive terminals on the proximal lateral dendrite, soma, and proximal
      ventral dendrite of both Mauthner cells. These results suggest that the octaval
      region contributes to bilateral inhibition of the Mauthner cells. The distal
      lateral dendrite of the ipsilateral Mauthner cell also showed a reduction in GAD
      immunoreactive terminals. This suggests that GABA mediates remote dendritic
      inhibition of this cell. GAD immunoreactive puncta also surrounded other large
      reticulospinal neurons, some of which are serially reiterated along the anterior
      posterior axis of the hindbrain. Thus, GABA may also exert an influence not only
      on the Mauthner cells, but also on other reticulospinal neurons.

PMID- 8132864
TI  - Crustacean cardioactive peptide-immunoreactive neurons in the hawkmoth Manduca
      sexta and changes in their immunoreactivity during postembryonic development.
AB  - An antiserum against crustacean cardioactive peptide was used, in indirect
      immunocytochemistry on whole-mounts and Vibratome sections, to map immunoreactive
      neurons at various stages of postembryonic development of the hawkmoth Manduca
      sexta. About 90 immunoreactive neurons were identified. Many of these cells are
      immunoreactive at hatching and persist into the adult stage; others become
      immunoreactive late in postembryonic development. During adult development,
      transient immunoreactivity is expressed in several cells in the subesophageal and
      thoracic ganglia. Two sets of immunoreactive neurons are found in the
      protocerebrum of larvae, but only one of these sets persists into the adult
      stage. Paired lateral interneurons and neurosecretory neurons are segmentally
      repeated in the abdominal ganglia and are present from the first larval stage to
      the adult; the abdominal interneurons project contralaterally to arborizations in
      adjacent ganglia, and some ascend to tritocerebral arborizations. The abdominal
      neurosecretory cells, which correspond to a pair of cells reported to contain
      bursicon, project posteriorly to neurohemal release organs. Motor neurons of
      dorsal external oblique abdominal muscles become immunoreactive in the fourth
      larval stage. Paired median neurosecretory cells of abdominal ganglia become
      immunoreactive during the fifth larval stage. The immunoreactive median and
      lateral abdominal neurosecretory cells are a subset of a group of cells known to
      contain cardioactive peptides. Paired lateral neurosecretory cells of the
      subesophageal ganglion become immunoreactive during pupation and project to the
      corpora cardiaca and aorta of the adult. Many of the neurons identified here are
      comparable to crustacean cardioactive peptide-immunoreactive cells described
      previously in locusts and the mealworm beetle.

PMID- 8132865
TI  - In vitro modulation of somatic glycine-like immunoreactivity in presumed
      glycinergic neurons.
AB  - Previous studies indicate that tuberculoventral and cartwheel cells in the dorsal
      cochlear nucleus as well as a group of stellate cells in the ventral cochlear
      nucleus are likely to be glycinergic. To test whether these neurons contain
      higher levels of free glycine than cells that are probably not glycinergic,
      immunocytochemical studies with antibodies against glycine conjugates were
      undertaken on slices of the murine cochlear nuclear complex. Present results show
      that the cell bodies of all three groups of neurons are immunolabeled. However,
      the somatic labeling of the tuberculoventral and cartwheel cells can be modulated
      by experimental conditions. In slices fixed immediately after cutting, many cell
      bodies in the deep layer of the dorsal cochlear nucleus (DCN), presumably
      tuberculoventral neurons, are labeled. As a slice is incubated in vitro, cell
      bodies in the deep layer of the DCN lose their glycine-like immunoreactivity.
      After 7 hours in vitro, labeled cells are absent in the deep DCN, but the
      immunoreactivity can be regained by electrically stimulating the auditory nerve
      for 20 minutes. The loss of immunoreactivity is prevented by electrical
      stimulation, by axotomy, and by inclusion of 0.8 microM tetrodotoxin, or 1 microM
      strychnine, or 50 microM colchicine or 50 microM beta-lumicolchicine in the
      bathing saline. Cartwheel cells retain their immunoreactivity during incubation
      in vitro without electrical stimulation, but lose it under two conditions. One is
      following a cut across the ventral cochlear nucleus (VCN) that severs most of
      their granule cell input, and the other is the inclusion of tetrodotoxin in the
      bathing saline. The labeling of cell bodies in the ventral cochlear nucleus and
      of puncta and processes is not changed by any of these experimental
      manipulations.

PMID- 8132866
TI  - GABAA/benzodiazepine receptor alpha 6 subunit mRNA in granule cells of the
      cerebellar cortex and cochlear nuclei: expression in developing and mutant mice.
AB  - The gamma aminobutyric acidA/benzodiazepine (GABAA/BZ) receptor is a multisubunit
      (alpha, beta, gamma, delta, and rho) ligand-gated chloride channel; there are
      several variants of the alpha, beta, and gamma subunits, each of which has been
      localized throughout the central nervous system. A large number of GABAA/BZ
      subunit variants are expressed within the cerebellar cortex. In previous studies
      from other laboratories, alpha 6 subunit mRNA has been reported to be present
      exclusively in cerebellar granule cells. The developmental expression of alpha 6
      mRNA in cerebellar and cochlear granule cells is of interest because it has been
      suggested that each of these cell types is derived from a common precursor pool.
      The polymerase chain reaction was used to generate a cDNA fragment encoding a
      portion of the M3-M4 intracellular loop of the alpha 6 subunit of the GABAA/BZ
      receptor. A [35S] riboprobe, transcribed from this cDNA fragment, was used to
      examine the expression of the alpha 6 subunit mRNA by in situ hybridization in
      developing normal mice and in adult mutant mice with known deficits in synaptic
      circuitry. A strong hybridization signal was observed over the granule cell
      layers of both the cerebellum and cochlear nuclei in adult mice. The signal over
      the cochlear nuclei appeared after birth toward the end of postnatal week 1,
      coinciding with the appearance of labeling in the cerebellar cortex. The
      intensity of the hybridization signal in both regions increased rapidly until
      postnatal day 14, after which it increased more gradually, reaching adult levels
      during postnatal week 3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132867
TI  - Synaptic interrelationships between the optic tectum and the ipsilateral nucleus
      isthmi in Rana pipiens.
AB  - The nucleus isthmi is reciprocally connected to the ipsilateral optic tectum.
      Ablation of the nucleus isthmi compromises visually guided behavior that is
      mediated by the tectum. In this paper, horseradish peroxidase (HRP)
      histochemistry and electron microscopy were used to explore the synaptic
      interrelationships between the optic tectum and the ipsilateral nucleus isthmi.
      After localized injections of HRP into the optic tectum, there are retrogradely
      labeled isthmotectal neurons and orthogradely labeled fibers and terminals in the
      ipsilateral nucleus isthmi. These terminals contain round, clear vesicles of
      medium diameter (40-52 nm). These terminals make synaptic contact with dendrites
      of nucleus isthmi cells. Almost half of these postsynaptic dendrites are
      retrogradely labeled, indicating that there are monosynaptic tectoisthmotectal
      connections. Localized HRP injection into the nucleus isthmi labels terminals
      primarily in tectal layers B, E, F, and 8. The terminals contain medium-sized
      clear vesicles and they form synaptic contacts with tectal dendrites. There are
      no instances of labeled isthmotectal terminals contacting labeled dendrites.
      Retrogradely labeled tectoisthmal neurons are contacted by unlabeled terminals
      containing medium-sized and small clear vesicles. Fifty-four percent of the
      labeled fibers connecting the nucleus isthmi and ipsilateral tectum are
      myelinated fibers (average diameter approximately 0.6 microns). The remainder are
      unmyelinated fibers (average diameter approximately 0.4 microns).

PMID- 8132868
TI  - Clusterin (SGP-2): a multifunctional glycoprotein with regional expression in
      astrocytes and neurons of the adult rat brain.
AB  - Clusterin (SGP-2) is a newly described glycoprotein associated with several
      putative functions including responses to brain injury. This study reports the
      regional and cell type expression of clusterin mRNA and its encoded glycoprotein
      in the rat brain; a limited comparison was also done with the human brain. Using
      in situ hybridization combined with immunocytochemistry, we found that astrocytes
      and neurons may express clusterin mRNA in the normal adult brain. While
      astrocytes throughout the brain contained clusterin mRNA, there was regional
      selectivity for neuronal clusterin expression. In the striatum, clusterin mRNA
      was not detected in neurons. Only a subset of substantia nigra dopaminergic
      neurons or locus ceruleus noradrenergic neurons (tyrosine hydroxylase
      immunopositive) contained clusterin mRNA. However, neuronal clusterin mRNA was
      prevalent in pontine nuclei and in the red nucleus of the midbrain tegmentum.
      Similarly, clusterin mRNA was prevalent in both rat and human hippocampal neuron
      specific enolase immunopositive pyramidal neurons, although rat CA1 neurons had
      less mRNA than CA2-CA3 neurons. Monotypic primary cell cultures from the neonatal
      rat showed clusterin mRNA in both neurons and astrocytes, but not in microglia.
      By immunocytochemistry, no clusterin immunopositive glia were observed in any
      region of the rat brain, confirming previous studies. However, clusterin
      immunopositive cells (putative neurons) were observed in the Purkinje cell layer
      of the cerebellum, medial and interposed cerebellar nuclei, trigeminal motor
      nucleus, and red nucleus. Finally, in vitro studies suggest that astrocytes, but
      not neurons, secrete clusterin, which is pertinent to clusterin immunodeposits
      found after experimental lesioning.

PMID- 8132869
TI  - Morphology of developing rat genioglossal motoneurons studied in vitro: changes
      in length, branching pattern, and spatial distribution of dendrites.
AB  - The aim of this study is to describe the postnatal change in dendritic morphology
      of those motoneurons in the hypoglossal nucleus that innervate the genioglossus
      muscle. Forty genioglossal (GG) motoneurons from four age groups (1-2, 5-6, 13
      15, and 19-30 postnatal days) were labeled by intracellular injection of
      neurobiotin in an in vitro slice preparation of the rat brainstem and were
      reconstructed in three-dimensional space. The number of primary dendrites per GG
      motoneuron was approximately 6 and remained unchanged with age. The development
      of these motoneurons from birth to 13-15 days was characterized by a
      simplification of the dendritic tree involving a decrease in the number of
      terminal endings and dendritic branches. Motoneurons lost their 6th-8th order
      branches, in parallel with an elongation of their terminal dendritic branches
      maintaining the same combined dendritic length. The elongation of terminal
      branches was attributed to both longitudinal growth and the apparent lengthening
      caused by resorption of distal branches. The elimination of dendritic branches
      tended to increase the symmetry of the tree, as revealed by topological analysis.
      Later, between 13-15 days and 19-30 days, there was a reelaboration of the
      dendritic arborization returning to a configuration similar to that found in the
      newborn. The length of terminal branches was shorter at 19-30 days, while the
      length of preterminal branches did not change, suggesting that the proliferation
      of branches at 19-30 days takes place in the intermediate parts of terminal
      branches. The three-dimensional distribution of dendrites was analyzed by
      dividing space into six equal volumes (hexants). This analysis revealed that GG
      motoneurons have major components of their dendritic tree oriented in the
      lateral, medial, and dorsal hexants. Further two-dimensional polar analysis
      (consisting of eight sectors) revealed a reconfiguration of the tree from birth
      up to 5-6 days involving resorption of dendrites in the dorsal, dorsomedial, and
      medial sectors and growth in the lateral sector. Later in development (between 13
      15 days and 19-30 days), there was growth in all sectors, but of a greater
      magnitude in the dorsomedial, medial, and dorsolateral sectors.

PMID- 8132870
TI  - Auditory nerve terminals in the cochlear nucleus magnocellularis: differences
      between low and high frequencies.
AB  - Primary auditory nerve fibers were labelled in the barn owl by localized
      horseradish peroxidase (HRP) injections into the cochlear nucleus angularis. They
      were followed to their terminal sites in the hearing organ (basilar papilla),
      confirming that they were auditory, and to the cochlear nucleus magnocellularis.
      The terminal sites of low-frequency fibers within nucleus magnocellularis always
      included an area previously described as the lagenar part, i.e., an area
      receiving primary input which is probably only vestibular. Furthermore, a number
      of differences were recognized between these low-frequency (up to 0.64 kHz) and
      the high-frequency (1.8 kHz and above) auditory nerve projections to nucleus
      magnocellularis. Most importantly, the collaterals given off by low-frequency
      fibers into the nucleus typically showed multiple terminal branching, with both
      en passant and terminal bouton-like swellings. High-frequency fiber collaterals,
      in contrast, terminated unbranched in a single endbulb of Held. Nucleus
      magnocellularis is the first station in a brainstem auditory pathway processing
      stimulus timing information, coded through neuronal phase locking. The prominent
      difference in terminal shape found between its low- and high-frequency input
      fibers is interpreted as reflecting different requirements of the absolute
      temporal precision for significant phase locking. Terminals in the shape of
      endbulbs of Held are probably a specialization to improve the temporal precision
      of synaptic transmission, allowing phase locking to higher frequencies.

PMID- 8132871
TI  - Age-related increase in the total number of corticotropin-releasing hormone
      neurons in the human paraventricular nucleus in controls and Alzheimer's disease:
      comparison of the disector with an unfolding method.
AB  - It has been hypothesized that the corticotropin-releasing hormone (CRH) neurons
      of the hypothalamic paraventricular nucleus (PVN) become hyperactive with age,
      and even more so in Alzheimer's disease. This hyperactivity could be due to an
      increased production of CRH per neuron, or an increased number of PVN neurons
      producing CRH, or both. As a first step in elucidating which of these biological
      mechanisms might be operative, we have estimated the absolute number of CRH
      immunoreactive neurons in the PVN of 10 human control subjects between 36 and 91
      years of age and 10 Alzheimer patients between 40 and 97 years of age. CRH
      neurons were immunocytochemically detected in 6 microns paraffin sections with
      the aid of a highly specific monoclonal antibody to CRH. The antibody signal was
      amplified by the biotin-streptavidin and alkaline phosphatase methods. The
      absolute number of CRH neurons in the PVN was obtained by multiplying the number
      of CRH neurons in a unit volume (NV) by the total volume of the PVN. Two
      different methods were used to estimate the NV: an unfolding method and a
      disector method (about three times more time-consuming). Compared to the
      disector, the unfolding method consistently yielded a lower cell number for all
      patients by 38% (+/- 2.8%; mean +/- SEM). However, both methods yielded an
      increase in the absolute number of CRH neurons in control and Alzheimer patients
      with age. No statistically significant difference in the absolute number of CRH
      neurons was found between control and Alzheimer patients with both methods. The
      age-dependent increase in the absolute number of CRH neurons within the PVN of
      both control and Alzheimer patients is interpreted as a sign of activation of the
      CRH neurons with age.

PMID- 8132872
TI  - The immunohistology of cutaneous neoplasia: a practical perspective.

PMID- 8132873
TI  - Dermal dendrocytes are decreased in collagenomas.
AB  - Dermal dendrocytes comprise a subset of spindle-shaped cells which normally
      reside in the dermis. While they appear to play some role in the
      reticuloendothelial system, their exact functions have not been completely
      elucidated. In addition to their purported immunologic functions, it has been
      suggested that dermal dendrocytes may play an inhibitory role in the regulation
      of dermal collagen synthesis. We examined 7 collagenomas with antibodies directed
      against factor XIIIa (FXIIIa) in order to test the hypothesis that dermal
      dendrocytes were focally diminished in these hamartomatous overgrowths of
      collagen. In all cases, there was a marked diminution in the number of FXIIIa
      positive cells in the lesional dermis when compared to the surrounding dermis.
      Our data support the hypothesis that dermal dendrocytes may be involved in
      regulation of collagen synthesis.

PMID- 8132874
TI  - The molecular diagnosis of cutaneous infection.
AB  - Molecular biologic techniques are having an impact on many different aspects of
      medicine. In the realm of infectious agents, they are enhancing our diagnostic
      capabilities, allowing earlier detection of infection, avoiding the need of
      culturing infectious agents for the purpose of diagnosis, and broadening our
      concepts to include the presence of infection in the absence of a culturable
      agent or serologic evidence of infection. As one might expect, the applicability
      of these techniques varies with the type of infectious agent being considered.
      For example, in most bacterial infections the infectious agent can be cultured
      and accurately identified within 48 hours. It is therefore unlikely that
      molecular diagnostic techniques will replace the "gold standard" of culture in
      instances of bacterial infection. Mycobacterial and spirochetal agents, by
      contrast, do not fall into this category. Although the rapid growers
      (Mycobacterium fortuitum and Mycobacterium chelonae) pose little problem because
      they can be cultured within 1 week, M. tuberculosis, M. leprae and the slow
      growing mycobacteriae require long intervals to culture and/or identify. These
      organisms may in the future be identified with molecular diagnostic techniques.
      In the group of spirochetal pathogens, Treponema pallidum infection is, for the
      most part, easily diagnosed with serologic studies. In early seronegative cases,
      spirochetes can be detected in primary inoculation lesions by darkfield
      microscopy or in tissue sections with appropriate stains. Conversely, detection
      of Borrelia burgdorferi is currently fraught with difficulties. Tissue sections
      stained for these spirochetes are difficult to interpret, and serologic studies
      have shown widely variable results. The polymerase chain reaction has already
      been applied to the study of Borrelia infection with encouraging early
      results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132875
TI  - Self assessment.

PMID- 8132876
TI  - Papillary cystadenoma of the lower lip mimicking hidradenoma papilliferum.

PMID- 8132877
TI  - Thermal behavior of bovine lactoferrin in water and its relation to bacterial
      interaction and antibacterial activity.
AB  - Heat-induced enthalpy changes in different forms of bovine lactoferrin in water
      were examined by differential scanning calorimetry. Two thermal transitions with
      varying enthalpies were observed, depending on the iron-binding status of the
      protein. Iron-saturated lactoferrin was more resistant to heat-induced changes
      than was the apolactoferrin. Native lactoferrin had two transitional peaks, and
      pasteurization affected only the low temperature transition. Iron-saturated
      lactoferrin revealed a single transitional peak that was resistant to
      pasteurization. However, both protein forms were completely denatured by UHT. The
      effect of pasteurization and UHT on the protein interaction capacity with
      bacteria was examined in a 125I-labeled lactoferrin binding-inhibition assay. The
      ability of native and iron-saturated lactoferrins to bind various bacterial
      species was unaffected by pasteurization. However, UHT treatment decreased this
      interaction capacity. Native lactoferrins, both unheated and pasteurized, showed
      similar antibacterial properties and moderately inhibited Escherichia coli.
      However, this inhibitory capacity was lost after UHT treatment. Finally, iron
      saturated lactoferrin did not inhibit bacterial growth; neither pasteurization
      nor UHT could change this property. Thus, UHT seems to affect structural as well
      as certain biological properties of both native and iron-saturated bovine
      lactoferrins, and pasteurization seems to be a treatment of choice for products
      containing this protein.

PMID- 8132878
TI  - Effect of mammary-derived growth inhibitor on proliferation of MAC-T bovine
      mammary epithelial cells.
AB  - An established bovine mammary epithelial cell line (MAC-T) was used as a model to
      examine the effect of mammary-derived growth inhibitor on mammary epithelial cell
      proliferation. Prior to each proliferation assay, cells were synchronized in
      G1/G0 by culturing for 24 h without serum. Flow cytometry revealed that 90% of
      cells were in G1/G0, 4% in G2/M, and 6% in the S-phase after serum deprivation.
      Approximately 2 x 10(3) cells per well were seeded onto 24-well plates. Cells
      were incubated for 5 to 6 d with various amounts of mammary-derived growth
      inhibitor (0 to 100 ng/ml). Mammary-derived growth inhibitor and medium were
      changed daily. Mammary-derived growth inhibitor decreased mammary epithelial cell
      proliferation at .1 ng/ml. Synchronization of cells in G1/G0 was necessary for
      inhibition of cell proliferation. Cells not arrested by serum deprivation were
      not responsive to mammary derived-growth inhibitor. Inhibition of cell
      proliferation was transient and observed up to 96 h in culture. Mammary-derived
      growth inhibitor appears to act in vitro by inhibiting the resumption of
      stationary cell proliferation following starvation.

PMID- 8132879
TI  - Effect of somatotropin on changes in milk production and composition during
      coliform mastitis in periparturient cows.
AB  - The potential protective and therapeutic effects of bST during coliform mastitis
      in periparturient cows were evaluated. In a first study, 19 cows, classified as
      moderate or severe responders based on the respiratory burst activity of blood
      neutrophils, were treated with recombinant bST or vehicle 48 h after intramammary
      inoculation of Escherichia coli. Clinical status and changes in milk production
      and composition were compared in the four groups. In a second study, 8 cows
      received bST or vehicle 7 d before bacterial challenge. During mastitis, losses
      in milk production and compositional changes were most pronounced in infected
      glands and in severe responders. Milk production of bST cows recovered better
      than that of placebo cows. Recovery of milk components was accelerated in severe
      responders treated with bST, but not in moderate responders. Pretreatment of
      severe responders with bST enhanced milk production before infection, protected
      the mammary glands from excessive loss of milk during the subsequently induced
      coliform mastitis, and accelerated normalization of milk composition. In
      conclusion, the beneficial effects of bST upon normalization of milk production
      and composition in periparturient cows suffering from coliform mastitis seem to
      be restricted to the severe responders. In severe responders that had been
      treated with bST, changes observed during mastitis resembled those in moderate
      responders treated with the placebo.

PMID- 8132880
TI  - Serum urea nitrogen and conception rate: the usefulness of test information.
AB  - Total of 627 AI in 332 Holstein cows in nine herds were used to examine the
      relationship between serum urea N and conception rate. Cows were assigned
      randomly to one of three isocaloric diets varying in protein degradability and
      content. The AI occurred from 50 to 150 DIM. Mean serum urea N for each cow from
      50 to 150 DIM was used to examine conception rate and serum urea N. The clinical
      interpretation of serum urea N on conception rate is evaluated using Bayes
      theorem from two approaches (dichotomization vs. continuous). Test information
      resulting from dichotomization of serum urea N into high and low categories
      (maximizing the average of test sensitivity and specificity) is compared with
      likelihood ratio approaches allowing a continuous measure. Likelihood ratio test
      indicates that conception rate decreases with serum urea N of > 14.9 mg/dl, but
      dichotomized test suggests that the decrease does not occur until serum urea N is
      > 20 mg/dl.

PMID- 8132881
TI  - Response of early lactation cows to fat supplementation in diets with different
      nonstructural carbohydrate concentrations.
AB  - Twenty-four high producing (36.7 kg/d, initially) Holstein cows in early
      lactation were used in a 63-d lactation trial to study the effects of low (28%),
      medium (31%), and high (37%) nonstructural carbohydrate concentrations in diets
      with added fat. Diets with isonitrogenous (17% CP) and fed as TMR with 41%
      sorghum silage. Nonstructural carbohydrate concentrations were altered by
      substitution of corn gluten feed and soybean hulls (50:50) for wheat and corn in
      the concentrate portion of the diet. Fat was added at 3% of DM in the form of
      yellow grease. Production of milk (38.5, 38.9, and 40.4 kg/d) and 3.5% FCM (38.2,
      37.0, and 37.6 kg/d) was not significantly different for the cows fed low,
      medium, and high nonstructural carbohydrate diets, respectively. Milk fat
      percentages (3.47, 3.22, and 3.10%) decreased, and milk output per unit of DMI
      (1.5, 1.6, and 1.7) increased, as nonstructural carbohydrate concentration
      increased. Increasing nonstructural carbohydrate concentrations of the diet
      increased digestibilities of DM (58.4, 60.6, and 61.5%) and nonstructural
      carbohydrates (76.5, 79.6, and 80.4%) and decreased digestibilities of NDF (44.3,
      43.7, and 40.6%) and ADF (46.3, 45.2, and 38.8%). Altering nonstructural
      carbohydrate content of the diet had no effect on AA supply to or uptake by the
      mammary gland or efficiency of utilization of AA for milk protein synthesis.

PMID- 8132882
TI  - Lack of response to addition of degradable protein to a low protein diet fed to
      midlactation dairy cows.
AB  - Midlactation Holstein cows (n = 24, 12 primiparous) were subjected to four
      dietary treatments arranged in six Latin squares. Cows were assigned to squares
      according to parity and previous production within parity. Diets contained 53 to
      55% DM from corn silage, and the remaining DM was from concentrates. The basal
      diet contained 13.9% CP with 9.5% rumen-degraded and 4.4% undegraded intake
      protein. Three other treatments were formulated to give one diet with more
      degradable true protein than the basal (11.9% degraded intake protein, 4.3%
      undegraded intake protein); another with urea added to the basal (12.2% degraded
      intake protein, 4.5% undegraded intake protein); and a third with additional
      undegraded protein added to the basal (8.3% degraded intake protein, 7.2%
      undegraded intake protein). Milk fat and protein concentration were unaffected by
      diet in all squares. Only the highest producing cows responded significantly to
      increased undegraded intake protein; milk production was 30.8, 30.9, 31.6, and
      33.2 kg/d for basal, added degradable true protein, added urea, and added
      undegraded protein, respectively. Corresponding protein productions were 913,
      929, 927, and 1004 g/d for these cows. Neither degradable true protein nor
      degradable N increased milk production in the highest producing cows, suggesting
      that microbial protein production was not limited by the amount of degradable
      protein in the basal diet. For midlactation, multiparous, and primiparous cows
      producing < 30 and 25 kg of milk/d, respectively, the protein content of the
      basal ration appeared to be adequate.

PMID- 8132883
TI  - Effect of microbial inoculants on the nutritive value of corn silage for
      lactating dairy cows.
AB  - Two experiments were conducted to evaluate the effect of microbial inoculation on
      the composition and nutritive value of corn silage for lactating cows. In
      Experiment 1, forage was untreated or treated at ensiling with Pioneer 1174 or
      Ecosyl silage inoculants. Forage was offered for free choice consumption, and
      concentrate was fed by a computerized feeder. Treatment with 1174 inoculant had
      little effect on silage composition and no effect on cow performance. Silage
      treated with Ecosyl inoculant had greater lactic acid content, but also greater
      acetic acid and ammonia N contents. Production of 3.5% FCM was greatest from cows
      fed silage treated with Ecosyl. In Experiment 2, silage was untreated or treated
      with Ecosyl and fed in a TMR. Inoculation had no effect on silage composition but
      increased 3.5% FCM production and DMI as length of time on treatment increased.
      Microbial inoculation can improve the nutritive value of corn silage for
      lactating cows even if changes in fermentation end products are minimal.

PMID- 8132884
TI  - Body measurements, metritis, and postpartum performance of first lactation cows.
AB  - Effects of herd, sire, season, body height, BW, age at calving, and metritis on
      future performance of first lactation cows were evaluated in eight commercial
      Israeli Holstein herds. Short, heavy first lactation cows had an odds ratio of
      3.1 of incidence of metritis at calving compared with all others; 648 first
      lactation cows were measured at wk 1 postpartum. Sire, herd, age, height, season,
      and BW contributed to peak milk yield. Metritis did not affect peak yield. Herd,
      sire, height, and age contributed to mature equivalent corrected 305-d milk
      yield. No effect was found for BW, season, or metritis. Herd was the only
      variable contributing to month of peak yield and rate of monthly drop in yield.
      Interactions between BW, height, and incidence of metritis were significant.
      Tall, heavy first lactation cows with metritis peaked higher and yielded more
      than those without metritis. Short, light first lactation cows with metritis
      yielded less and peaked lower than their healthy counterparts. Metritis did not
      affect future fertility, but season and the interaction between BW and height
      did. Tall, heavy first lactation cows had a lower pregnancy rate from first AI,
      independent of milk yield. The relative importance of height as a predictor of
      future milk yield is underestimated. The interaction between height and BW may
      have an antagonistic effect on yield and fertility.

PMID- 8132885
TI  - Associations of bovine lymphocyte antigens with milk and meat production traits
      of Norwegian cattle.
AB  - Bovine lymphocyte antigens of class I were defined for 434 AI bulls of Norwegian
      Cattle, which is a dual purpose breed. The antigens w16, A2, and A8 occurred at
      highest frequencies. A gene substitution model was used to compare bovine
      lymphocyte antigens with total breeding value and breeding values for milk yield,
      milk fat percentage, milk protein percentage, and meat production. Several bovine
      lymphocyte antigens were significantly associated with the traits in question:
      low fat percentage was associated with A8, A10(w50), and A11; high milk protein
      percentage with A13; and low meat production with the rare antigen w1.
      Associations of the bovine lymphocyte antigens and milk yield were not
      significant.

PMID- 8132886
TI  - Associations of breeding values for disease traits and genetic markers in dairy
      cattle estimated with a mixed model.
AB  - Since 1985, all veterinary treatments on dairy cows in Sweden have been recorded
      and utilized for estimation of sire breeding values for resistance to clinical
      mastitis and to diseases other than clinical mastitis. The purpose of the present
      investigation was to study the relationship of blood groups and blood protein
      polymorphisms with these traits and to extend a method previously applied to
      international comparisons of dairy sires for milk production to estimation of
      marker gene effects. The data comprised 1171 AI sires of the Swedish Red and
      White dairy breed that had a blood typing record and breeding values for disease
      resistance. Information was available on the breeding values of sires, the number
      of daughters of each sire, and the relationships among sires. This information
      was used to deregress the sire breeding values to average daughter performances,
      which then were analyzed by a mixed linear model. The reduction in error variance
      that was due to inclusion of the markers in the model was small. Several
      substitution effects of the markers were statistically significant. The largest
      effects corresponded to a deviation of .7 percentage units for the frequency of
      veterinary treatments among the average daughters of the sires.

PMID- 8132887
TI  - Interaction of age and month of calving with year of calving for production
      traits of Ontario Holsteins.
AB  - Production records of 835,789 Ontario Holsteins calving between 1958 and 1990
      were used to determine the presence of an interaction of the age and month of
      calving of cows with the year of calving for production of milk and fat and fat
      percentage. An animal model was employed including the effects of herd-year
      season of calving, interaction of age and month of calving with year of calving,
      animal additive genetic effects, and permanent environmental effects. Tests for
      interactions of age with year within months of calving were significant for
      production of milk and fat, but not for fat percentage. Tests for interactions of
      month with year within age groups were significant for only a few age groups in
      the second and third parties. The implication of these findings on genetic
      evaluation is that an interaction of age and month of calving with year of
      calving should be included in the animal model for genetic evaluations rather
      than preadjusting production for age and month of calving.

PMID- 8132888
TI  - Regulation of the soluble form of nicotinamide adenine dinucleotide phosphate
      specific isocitrate dehydrogenase from lactating bovine mammary gland: effects of
      metabolites on activity and structure.
AB  - The cytosolic form of NADP+: isocitrate dehydrogenase, a primary source of the
      NADPH required for de novo fatty acid synthesis in lactating bovine mammary
      gland, was studied to determine possible mechanisms of regulation by metabolites.
      The enzymatic reduction of NADP+ exhibits lag-burst (hysteretic) kinetics that
      are eliminated by the noncatalytic binding of the substrate, a complex (1:1) of a
      metal ion (Mn2+ or Mg2+) and isocitrate. Preincubation of the enzyme with metal
      citrate complex also nearly abolished the lag or activation time. In steady-state
      experiments, analyses of velocity versus metal-citrate complex as a binding
      isotherm, following the assumptions of Wyman's theory of thermodynamic linkage,
      showed that binding of metal-citrate complex could both stimulate and inhibit the
      enzyme. This analysis suggested hyperactivation by binding to sites with an
      average dissociation constant of .25 mM, inhibition by binding to sites with an
      average dissociation constant of 3.83 mM, and modulation (reactivation) by
      binding to sites with an average dissociation constant of 1.54 mM. Conformational
      changes induced by the binding of ligands were assessed using circular dichroism.
      The results suggest that binding of metal-isocitrate induces a conformational
      transition involving tyrosyl residues that is related to the altered kinetic
      processes. Reexamination of Michaelis-Menten kinetics using non-linear regression
      analysis also demonstrated hyperactivation of enzyme activity by metal-isocitrate
      with a dissociation constant equal to 21 microM (which is nearly seven times
      greater than the Michaelis constant). Concentration ranges observed for these
      transitions are compatible with physiological conditions, suggesting that
      complexes of metal-citrate and metal-isocitrate serve to modulate the activity of
      NADP+: isocitrate dehydrogenase.

PMID- 8132889
TI  - Bovine mammary lactoferrin: implications from messenger ribonucleic acid (mRNA)
      sequence and regulation contrary to other milk proteins.
AB  - The regulation of bovine mammary lactoferrin, an important component of the
      antimicrobial defenses of the mammary gland, is poorly understood compared with
      the other milk proteins. The complete sequence for bovine lactoferrin mRNA shows
      it to be highly homologous to other lactoferrins and transferrins. However,
      regional differences in the deduced AA sequence of bovine lactoferrin compared
      with human lactoferrin and transferrin imply functional differences between them.
      Steady-state levels of bovine lactoferrin mRNA (by Northern blot) in the bovine
      mammary gland indicate that bovine lactoferrin expression is minimal in the
      developing and lactating gland but is strongly induced by mammary involution. The
      overall regulation of bovine lactoferrin in the mammary gland appears to be
      contrary to that of the other milk proteins. Features identified in the mRNA of
      bovine mammary lactoferrin may contribute to the differences in regulation
      between lactoferrin and other bovine milk proteins and to differences in
      concentrations of lactoferrin in milk across species. Lactoferrin secretion by
      bovine mammary cells grown in vitro does not appear to be dependent on prolactin
      and shows regulation by substratum, serum, and cell population to be different
      from that for casein. In contrast to casein, efficient secretion of lactoferrin
      from the cell does not require detachment of collagen substratum.

PMID- 8132890
TI  - A review of the molecular and cellular biology of butyrophilin, the major protein
      of bovine milk fat globule membrane.
AB  - The molecular and cellular biology of the milk protein butyrophilin is reviewed.
      Butyrophilin constitutes more than 40% by weight of the total protein associated
      with the fat globule membrane of bovine milk. Closely related proteins are
      abundant in the fat globule membranes of many other species. Butyrophilin is
      synthesized as a peptide of 526 amino acids with an amino-terminal hydrophobic
      signal sequence of 26 amino acids, which is cleaved before secretion in
      association with the fat globule membrane. Hydropathy analysis and in vitro
      translation of butyrophilin mRNA indicate that the protein associates with
      membranes in a type I orientation via a single stretch of 27 hydrophobic amino
      acids in the approximate middle of the sequence. Evidence that butyrophilin is
      incorporated into fat globule membrane as a transmembrane protein and as a
      cytoplasmically oriented peripheral component is discussed. The carboxy-terminal
      sequence of butyrophilin is significantly homologous to two other proteins: ret
      finger protein and the 52-kDa nuclear antigen A of Sjogren's syndrome. Expression
      of bovine butyrophilin mRNA correlates with the onset of milk fat secretion
      toward the end of pregnancy and is maintained throughout lactation. The possible
      function of butyrophilin in the secretion of milk lipid droplets is discussed.

PMID- 8132891
TI  - Lipid metabolism in the rumen.
AB  - Recent advances in ruminal lipid metabolism have focused primarily on
      manipulation of physicochemical events in the rumen aimed at two practical
      outcomes: 1) control of antimicrobial effects of fatty acids so that additional
      fat can be fed to ruminants without disruption of ruminal fermentation and
      digestion and 2) regulation of microbial biohydrogenation to alter the absorption
      of selected fatty acids that might enhance performance or reduce saturation of
      meat and milk. Properties of lipids that determine their antimicrobial effects in
      the rumen include type of functional group, degree of unsaturation, formation of
      carboxylate salts, and physical association of lipids with surfaces of feed
      particles and microbes. The mechanism of how lipids interfere with ruminal
      fermentation is a complex model involving partitioning of lipid into the
      microbial cell membrane, potency of the lipid to disrupt membrane and cellular
      function, physical attachment of microbial cells to plant surfaces, and
      expression and activity of microbial hydrolytic enzymes. Lipolytic and
      hydrogenation rates vary with forage quality (stage of maturity and N content),
      surface area of feed particles in the rumen, and structural modifications of the
      lipid molecule that inhibit attack by bacterial isomerases.

PMID- 8132892
TI  - Lipid absorption and transport in ruminants.
AB  - The objective of this paper is to review new insights on the biological
      mechanisms of absorption and transport of lipid in ruminants, especially the
      modern concepts and analytical methods used in studies on structural properties
      and intravascular and tissue metabolism of lipoproteins and their factors of
      variation. The intestinal absorption of lipids (including long-chain fatty acids)
      is detailed, and variations in the qualitative and the quantitative aspects of
      absorption with diet composition, especially for high fat diets, are presented.
      Also, structural properties and distribution characteristics of lipoprotein
      classes in different lymphatic and blood vessels are compared across several
      animal species. Physicochemical and hydrodynamic properties of the lipoprotein
      particles and their apolipoprotein moieties are given for the main classes of
      lipoproteins. Finally, lipoprotein metabolism is discussed in relation to
      development and physiological, nutritional, and hormonal status. Intravascular
      metabolism of lipoproteins, including the role of lipolytic enzymes and lipid
      transfer proteins, is presented. Characteristics of the intestinal and hepatic
      synthesis of lipoproteins and apolipoprotein fractions are compared, especially
      through experiments stimulating the hepatic secretion of triglyceride-rich
      lipoproteins. Different methods of measurement of lipoprotein tissue uptake or
      secretion in ruminants are discussed.

PMID- 8132893
TI  - Etiology of lipid-related metabolic disorders in periparturient dairy cows.
AB  - Plasma NEFA concentrations increase prior to and at parturition, resulting in
      increased fatty acid uptake by the liver, fatty acid esterification, and
      triglyceride storage. Liver triglyceride concentration increases four- to
      fivefold between d 17 prior to calving and d 1 following calving. Increases in
      liver triglyceride following calving do not appear to be dramatic. Severity of
      fatty liver 1 d postpartum is correlated negatively with feed intake 1 d
      prepartum. Export of newly synthesized triglyceride as very low density
      lipoprotein occurs slowly in ruminants and is a major factor in the development
      of fatty liver. Nutritional strategies to minimize the elevation in plasma NEFA
      prior to calving results in lower liver triglyceride at calving. Fatty liver
      probably precedes clinical spontaneous ketosis. Liver triglyceride to glycogen
      ratio may be used to predict susceptibility of cows to ketosis. Consequently,
      strategies to reduce liver triglyceride at calving may decrease incidence of
      ketosis. Research to determine methods to reduce fatty acid delivery to the liver
      or to enhance hepatic export of very low density lipoprotein near calving is
      warranted. Identification of the cause for the slow rate of assembly and
      secretion of hepatic very low density lipoprotein in ruminants will be required
      to assess the feasibility of increasing export of very low density lipoprotein.

PMID- 8132894
TI  - Dietary fat and adipose tissue metabolism in ruminants, pigs, and rodents: a
      review.
AB  - Effects of dietary fat on dairy cows are reviewed. Dietary fat did not affect
      gain in BW or body condition score after peak lactation but tended to increase BW
      loss during early lactation and body fat deposition in growing cattle. Dietary
      fat decreased de novo fatty acid synthesis in adipose tissue. Basal FFA release
      from adipose tissue in vitro and beta-adrenergic lipolytic responses were
      increased by protected polyunsaturated fatty acids. Dietary fat increased body
      fat in growing pigs and decreased BW loss in lactating sows. Dietary fat
      decreased de novo fatty acid synthesis and basal glycerol release in adipose
      tissue and tended to increase simultaneously beta-adrenergic lipolytic responses
      to increased membrane fluidity. Dietary fat increased body fat in rats.
      Polyunsaturated fatty acids were sometimes less efficient than saturated ones in
      increasing body fat. Lipoprotein lipase activity in adipose tissue generally
      decreased. Hepatic fatty acid synthesis was decreased sharply by polyunsaturated
      fatty acids, and adipose tissue response was less important. beta-Adrenergic
      stimulated lipolysis decreased, and fatty acid esterification increased,
      particularly from saturated fatty acids. A trend toward insulin resistance, which
      was more marked with saturated fatty acids, occurred in adipose tissue.

PMID- 8132895
TI  - The effects of masking on vibrotactile temporal summation in the detection of
      sinusoidal and noise signals.
AB  - Thresholds for the detection of vibrotactile signals of varied duration applied
      to the thenar eminence were measured in the absence of and in the presence of a
      masking stimulus. Signals were 250- and 500-Hz sinusoids and noise bursts with
      bandwidth limited to 250-1000 Hz. The masking stimulus was either a 250-Hz
      sinusoid, which was presented in phase with the signal when it was sinusoidal, or
      noise. Changes in threshold as a function of changes in signal duration were
      found which were predicted accurately from Zwislocki's theory [J. Acoust. Soc.
      Am. 32, 1046-1060 (1960)] of temporal summation when the signal was detected by
      the Pacinian channel, but not when it was detected by a non-Pacinian channel
      (NP). However, when either the signal or the masking stimulus or both were noise,
      NP thresholds were affected by changes in signal duration. Only when the signal
      and masking stimuli were both sinusoids were NP thresholds independent of signal
      duration. It is concluded that signal duration effects in the NP channel are not
      due to temporal integration, but rather to increases in information about the
      signal content provided to the subject as exposure duration is increased.

PMID- 8132896
TI  - A quantitative model of voice F0 control.
AB  - A mathematical model of the larynx, based on biomechanical principles, is
      described. Components represented include two cartilage elements (cricoid with
      locked arytenoids, and thyroid), three muscles (thyroarytenoid [TA], cricothyroid
      pars rectus [CTr], and cricothyroid pars oblique [CTo]), and two ligaments
      (cricothyroid and vocal ligaments), as well as subglottal pressure (PS). For any
      combination of muscle activities and PS level, equilibrium positions and tensions
      could be calculated for components in the system. The tensions and lengths of
      vocal fold elements were then used to calculate fundamental frequency (F0) of
      vocal fold vibration. Systematic variation of model muscle activation and PS
      patterns allowed study of the behavior of the model. TA activity tended to
      shorten the vocal folds; increased levels of CTr and CTo activity, and PS, had
      the opposite effect. Increased activity of any muscle tended to increase vocal
      fold tension, while PS increases were mainly ineffective. F0 was generally
      increased by increased CTr, CTo, and PS values. However, TA activity had a
      strongly nonmonotonic effect on F0. Best control of F0 could be achieved only by
      a process of co-contraction of all muscles at low frequencies, followed by
      sustained contraction of CTr and CTo with decreasing TA activity for F0's
      increasing above this low-frequency range. These results are discussed in terms
      of their possible implications for norma and abnormal voice production, and as a
      set of constraints for neural modeling efforts.

PMID- 8132897
TI  - Vowel identification in mixed-speaker silent-center syllables.
AB  - Strange [J. Acoust. Soc. Am. 85, 2135-2153 (1989b)] has demonstrated that there
      is sufficient information in the onsets and offsets of syllables, spoken in
      sentence context, to provide accurate identification of the vowel in the
      syllable. Verbrugge and Rakerd [Language Speech 29, 39-57 (1986)] and Andruski
      and Nearey [J. Acoust. Soc. Am. 91, 390-490 (1992)] have shown that such
      information is present in citation-form syllables even when the syllables begin
      with one speaker and end with another. These studies of "hybrid syllables,"
      however, reported relatively high error rates. In a perceptual experiment using
      /dVd/ syllables spoken in sentence context by a male and a female speaker,
      relatively low error rates were obtained for both "silent-center" syllables and
      "hybrid silent-center" syllables. It was concluded that the information specified
      over syllable onsets and offsets together for identification of vowels is speaker
      independent and that it was sufficient in most cases to specify the vowel. The
      acoustic patterns, represented as functions of log (F2/F1) over time, revealed
      potentially useful dynamic acoustic characteristics of co-articulated vowels.

PMID- 8132898
TI  - Effects of first formant onset frequency on [-voice] judgments result from
      auditory processes not specific to humans.
AB  - When F1-onset frequency is lower, longer F1 cut-back (VOT) is required for human
      listeners to perceive synthesized stop consonants as voiceless. K. R. Kluender
      [J. Acoust. Soc. Am. 90, 83-96 (1991)] found comparable effects of F1-onset
      frequency on the "labeling" of stop consonants by Japanese quail (coturnix
      coturnix japonica) trained to distinguish stop consonants varying in F1 cut-back.
      In that study, CVs were synthesized with natural-like rising F1 transitions, and
      endpoint training stimuli differed in the onset frequency of F1 because a longer
      cut-back resulted in a higher F1 onset. In order to assess whether earlier
      results were due to auditory predispositions or due to animals having learned the
      natural covariance between F1 cut-back and F1-onset frequency, the present
      experiment was conducted with synthetic continua having either a relatively low
      (375 Hz) or high (750 Hz) constant-frequency F1. Six birds were trained to
      respond differentially to endpoint stimuli from three series of synthesized /CV/s
      varying in duration of F1 cut-back. Second and third formant transitions were
      appropriate for labial, alveolar, or velar stops. Despite the fact that there was
      no opportunity for animal subjects to use experienced covariation of F1-onset
      frequency and F1 cut-back, quail typically exhibited shorter labeling boundaries
      (more voiceless stops) for intermediate stimuli of the continua when F1 frequency
      was higher. Responses by human subjects listening to the same stimuli were also
      collected. Results lend support to the earlier conclusion that part or all of the
      effect of F1 onset frequency on perception of voicing may be adequately explained
      by general auditory processes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132899
TI  - Effect of temporal envelope smearing on speech reception.
AB  - The effect of smearing the temporal envelope on the speech-reception threshold
      (SRT) for sentences in noise and on phoneme identification was investigated for
      normal-hearing listeners. For this purpose, the speech signal was split up into a
      series of frequency bands (width of 1/4, 1/2, or 1 oct) and the amplitude
      envelope for each band was low-pass filtered at cutoff frequencies of 0, 1/2, 1,
      2, 4, 8, 16, 32, or 64 Hz. Results for 36 subjects show (1) a severe reduction in
      sentence intelligibility for narrow processing bands at low cutoff frequencies (0
      2 Hz); and (2) a marginal contribution of modulation frequencies above 16 Hz to
      the intelligibility of sentences (provided that lower modulation frequencies are
      completely present). For cutoff frequencies above 4 Hz, the SRT appears to be
      independent of the frequency bandwidth upon which envelope filtering takes place.
      Vowel and consonant identification with nonsense syllables were studied for
      cutoff frequencies of 0, 2, 4, 8, or 16 Hz in 1/4-oct bands. Results for 24
      subjects indicate that consonants are more affected than vowels. Errors in vowel
      identification mainly consist of reduced recognition of diphthongs and of
      confusions between long and short vowels. In case of consonant recognition, stops
      appear to suffer most, with confusion patterns depending on the position in the
      syllable (initial, medial, or final).

PMID- 8132900
TI  - Auditory supplements to speechreading: combining amplitude envelope cues from
      different spectral regions of speech.
AB  - Many listeners with severe-to-profound hearing losses perceive only a narrow
      range of low-frequency sounds and must rely on speechreading to supplement the
      impoverished auditory signal in speech recognition. Previous research with normal
      hearing subjects [Grant et al., J. Exp. Psychol. 43A, 621-645 (1991)]
      demonstrated that speechreading was significantly improved when supplemented by
      amplitude-envelope cues that were extracted from various spectral regions of
      speech and presented as amplitude modulations of carriers with frequencies at or
      below the speech band from which the envelope was derived. This experiment
      assessed the benefit to speechreading provided by pairs of such envelope cues
      presented simultaneously. In general, greater improvements in speechreading
      scores were observed for pairs than for single envelopes when the carrier signals
      were chosen appropriately. However, when pairs of envelope signals were
      transposed to low frequencies, the benefit to speechreading was no better than
      the most effective single-band envelope signal tested, or for a low-pass-filtered
      speech signal with the same overall bandwidth. Suggestions for improving the
      efficacy of frequency-lowered envelope cues for hearing-impaired listeners are
      discussed.

PMID- 8132901
TI  - Difference limens for formant patterns of vowel sounds.
AB  - Studies of thresholds for discrimination of formant frequency variation in
      synthetic vowel sounds have been predominantly limited to variations in a single
      formant. Here, differences limens (DLs) are presented for multiformant variations
      expressed in measures of delta F and as distances in the auditory-perceptual
      space (APS) proposed by J. D. Miller [J. Acoust. Soc. Am. 85, 2114-2134 (1989)].
      DLs for four subjects were estimated along 102 synthetic vowel continua
      representing five patterns of formant variation [(1) single variation in F1; (2)
      single variation in F2; (3) parallel simultaneous variation in F1 and F2; (4)
      opposing simultaneous variation in F1 and F2; and parallel simultaneous variation
      in F1, F2, and F3] and 17 within- or between-category vowel sounds. Minimal
      uncertainty methodology was employed utilizing an adaptive up-down procedure with
      a cued, two-interval forced-choice (2IFC) task. The results of this experiment
      reflect smaller DLs for both single- and multiple-formant changes than have been
      found in the past and also suggest that discrimination of parallel multiformant
      variation is significantly better than opposing multiformant or single-formant
      variation.

PMID- 8132902
TI  - Development of the Hearing in Noise Test for the measurement of speech reception
      thresholds in quiet and in noise.
AB  - A large set of sentence materials, chosen for their uniformity in length and
      representation of natural speech, has been developed for the measurement of
      sentence speech reception thresholds (sSRTs). The mean-squared level of each
      digitally recorded sentence was adjusted to equate intelligibility when presented
      in spectrally matched noise to normal-hearing listeners. These materials were
      cast into 25 phonemically balanced lists of ten sentences for adaptive
      measurement of sentence sSRTs. The 95% confidence interval for these measurements
      is +/- 2.98 dB for sSRTs in quiet and +/- 2.41 dB for sSRTs in noise, as defined
      by the variability of repeated measures with different lists. Average sSRTs in
      quiet were 23.91 dB(A). Average sSRTs in 72 dB(A) noise were 69.08 dB(A), or 
      2.92 dB signal/noise ratio. Low-pass filtering increased sSRTs slightly in quiet
      and noise as the 4- and 8-kHz octave bands were eliminated. Much larger increases
      in SRT occurred when the 2-kHz octave band was eliminated, and bandwidth dropped
      below 2.5 kHz. Reliability was not degraded substantially until bandwidth dropped
      below 2.5 kHz. The statistical reliability and efficiency of the test suit it to
      practical applications in which measures of speech intelligibility are required.

PMID- 8132903
TI  - Acoustics of the tenor high voice.
AB  - The spectra of six tenors were analyzed at high pitches, F4 to B4. Because of the
      wide separation between harmonics, formant frequencies could not be extracted in
      the traditional way. Rather, an analysis-by-synthesis technique was used to match
      the spectra of a model to the measured spectra, using parameter optimization.
      Results suggest that tenors maintain their first formant frequencies well above
      the fundamental for all vowels except [u]. The purpose of this seems to be to
      distribute the acoustic energy between harmonics 2, 3, and 4 rather than to boost
      the fundamental. Tuning the first formant to the fundamental is a technique used
      effectively by sopranos but seems to be deliberately avoided by tenors in order
      to preserve a male quality.

PMID- 8132904
TI  - Auditory-nerve fiber representation of temporal cues to voicing in word-medial
      stop consonants.
AB  - The length of the interval between the onset of consonant closure and the onset
      of voicing in a following vowel is a temporal cue that may distinguish between
      consonants /d/ and /t/ in word-medial environments; this interval has been called
      the "consonant duration" [V. W. Zue and M. Laferriere, J. Acoust. Soc. Am. 66,
      1039-1050 (1979); S. Davis and W. V. Summers, J. Phon. 17, 339-353 (1989)]. The
      representation of this cue in the discharge patterns of chinchilla auditory-nerve
      fibers was measured. The two-syllable utterances /ida/, /ita/, /uda/, and /uta/
      were recorded by one male and one female talker. The onset of consonant closure
      produced discharge rate decreases in nearly all neurons. Either the release of
      closure or the onset of voicing for the second vowel could elicit an increase in
      discharge rate. The latencies of these discharge rate changes varied across
      populations of neurons. A neural measure of consonant duration was extracted from
      the pattern of latencies. The "encoded duration" was longer for utterances with a
      medial /t/ than for utterances with a medial /d/. For each utterance the encoded
      duration increased with increases in characteristic frequency. The variability of
      the encoded duration measure was small enough to preserve the distinction between
      utterances with different word-medial consonants. The variability of the encoded
      duration was large, relative to the acoustic differences between utterances that
      included the same medial consonant. This pattern of variability could contribute
      to the formation of perceptual categories by reducing the audibility of within
      category acoustic differences.

PMID- 8132905
TI  - Wiener kernel analysis of inner ear function in the American bullfrog.
AB  - The response of 17 primary auditory nerve fibers in the American bullfrog (Rana
      catesbeiana) to acoustic noise stimulation of the tympanic membrane was recorded.
      For each fiber, the first- and second-order Wiener kernels, k1 (tau 1) and k2
      (tau 1, tau 2), were computed by cross correlation of the stimulus and the
      response. The kernels revealed amplitude and phase characteristics of auditory
      filters of both phase-locking and non-phase-locking fibers. Wiener kernels of
      high- and midfrequency fibers (best frequency, BF > 500 Hz), implied a simple
      sandwich model, consisting of a cascade of a linear bandpass filter, a static
      nonlinearity, a linear low-pass filter, and a spike generator. The bandpass
      filter was at least of order 7, and had a linear phase response, for both the
      high- and the midfrequency fibers. Averaged across fibers, filter order 2, and
      cutoff frequency 451 Hz for the second filter in the model was observed. The
      responses of low-frequency fibers (BF < 500 Hz) could not be fit with the
      sandwich model, because the Fourier transform K2 (f1,f2) of the second-order
      Wiener kernel showed significant components at off-diagonal frequencies f1 not
      equal to +/- f2. The presence of these off-diagonal components shows that, in
      addition to the phase and gain characteristics of auditory filters, the Wiener
      kernel analysis reveals nonlinear two-tone interactions.

PMID- 8132906
TI  - The effect of nonsimultaneous on-frequency and off-frequency cues on the
      detection of a tonal signal masked by narrow-band noise.
AB  - Listeners' detection thresholds were measured for a 125-ms, 1-kHz tonal signal
      masked by a similarly gated 50-Hz-wide band of noise. A two-interval, adaptive,
      forced-choice procedure either with or without temporally surrounding cuing
      intervals containing 50-Hz-wide bands of noise was employed. When the cues were
      present, their center frequency was either 1 kHz (on-frequency) or 900 or 700 Hz
      (off-frequency). In the conditions of principal interest, the envelopes and phase
      modulations of the bands of noise were "frozen" across the four intervals that
      defined a trial, but were chosen randomly across trials. Thresholds were lowest
      with cues centered at 1 kHz and increased substantially when the center frequency
      of the cues was changed to 900 or 700 Hz. With cues centered at 700 Hz,
      performance was equivalent to that obtained without cues and with the masking
      noise "frozen" across the two intervals that defined a trial. A similar pattern
      of results was obtained with high-frequency stimuli, where sensitivity to fine
      structure information is greatly reduced. Roving the level of the stimuli over a
      40-dB range generally reduced sensitivity but did not greatly affect the overall
      pattern of the data. Thresholds obtained in the two-interval task with masking
      waveforms chosen randomly were compared with thresholds obtained when the masking
      waveform was "frozen" within, but not across trials. Differences in threshold
      appeared to be accounted for by the listeners' use of changes in the mean slope
      of the envelope of the noise produced by adding the tonal signal.

PMID- 8132907
TI  - Detection of unexpected tones with short and long durations.
AB  - The detectability of short and long unexpected tones masked by a continuous
      wideband noise was assessed using a probe-signal method. This method leads the
      listener to expect a target frequency by presenting the signal most often at that
      frequency, and only occasionally at other unexpected probe frequencies. The probe
      signal contour (percent correct as a function of probe frequency) was
      considerably broader with 5-ms than with 295-ms signals. However, auditory filter
      shapes measured using the notched-noise technique were very similar for those two
      signal durations, indicating that the results obtained in the probe-signal
      conditions do not simply reflect peripheral frequency selectivity. Further
      supporting this interpretation, probe tones having the same frequency but a
      different duration from the target were poorly detected. It is proposed that the
      subject listens through a time-frequency window whose location and shape in the
      time-frequency plane is determined by the duration and frequency of the target.

PMID- 8132908
TI  - Detection of unexpected tones in gated and continuous maskers.
AB  - The effect of gating a wideband masker on the detectability of tones having
      unexpected frequencies was assessed using a probe-signal method. This method
      leads the listener to expect a target frequency by presenting the signal most
      often at that frequency, and measures sensitivity to other unexpected frequencies
      via occasionally presented probe tones. For 295-ms signals, the probe-signal
      contours (percent correct as a function of probe frequency) of two of four
      subjects were considerably broader for a 295-ms masker than for a continuous
      masker. For 5-ms signals, the probe-signal contours of four of five subjects were
      quite broad and similar for both gated and continuous maskers. When the probe
      signal contours were expressed as the attenuation in decibels of the probes, the
      resulting "probe-signal filters" were frequently broader than auditory filters
      measured using notched noise in the same subjects. This suggests that subjects
      may monitor multiple auditory filters under some conditions in the probe-signal
      task. Signal threshold tended to be higher for conditions showing wider probe
      signal filters, indicating a potential link between changes in signal threshold
      due to masker gating and the number of frequency channels that are monitored.

PMID- 8132909
TI  - Further evidence against an across-frequency mechanism specific to the detection
      of frequency modulation (FM) incoherence between resolved frequency components.
AB  - Previously, Carlyon [J. Acoust. Soc. Am. 89, 329-340 (1991)] argued that there
      exists no across-frequency mechanism specific to the detection of frequency
      modulation (FM) incoherence, defined as a difference in FM phase, between pairs
      of resolved frequency components. Experiments are described which attempted to
      reconcile this conclusion with the results of two recent studies. Wilson et al.
      [J. Acoust. Soc. Am. 88, 1333-1338 (1990)] reported that the detection of FM
      imposed on a target component was impaired by the presence of an FM "interfering
      tone," and that the size of the effect depended on the FM coherence between
      interferer and target. Experiment 1 replicated their findings but showed, by
      using low-pass and wideband noise, that its dependence on FM coherence was
      consistent with the detection of combination tones and of beating between the
      interferer and target. Cohen and Chen [J. Acoust. Soc. Am. 92, 766-722 (1992)]
      reported that the detection threshold for an FM signal was higher when it was
      masked by two components modulated coherently with it than when the masker and
      signal modulations were incoherent. Experiment 2 showed that, when the masker
      consisted of eight components, thresholds were largely determined by the
      modulation coherence between the signal and the masker component closest to it in
      frequency. Experiment 3 presented evidence that Cohen and Chen's findings were
      influenced by harmonicity between the masker and signal, even in conditions which
      attempted to control it. Experiment 4 replicated another of Cohen and Chen's
      findings, that when the masker modulation was held constant and the signal FM
      depth varied, some listeners' thresholds reached a maximum when the masker and
      signal FM depths were equal. By manipulating the frequency ratio between masker
      and signal, it was shown that this finding, too, could be attributed to
      harmonicity between the signal and one of the masker components. Finally,
      experiment 5 replicated Carlyon's (1991) findings at a higher sensation level and
      with a different pattern of modulation than used previously.

PMID- 8132910
TI  - Improving the detectability of a brief tone in noise using forward and backward
      masker fringes: monotic and dichotic presentations.
AB  - A brief tonal signal simultaneously masked by a brief noise burst became easier
      to hear when the masker duration was increased. The signal was a 1000-Hz tone, 4
      ms in duration; the masker was a wideband noise having a spectral notch 1400 Hz
      wide centered at 1000 Hz. Compared to performance with a 22-ms burst masker,
      average detection threshold across five subjects improved by 15 dB when a 150-ms
      masker "fringe" preceded the signal (forward fringe), and by 9 dB when the masker
      fringe followed the signal (backward fringe). Little improvement was observed in
      either condition when the fringe was presented to the ear contralateral to the
      signal/burst complex. However, when the fringe was presented to both ears and the
      signal/burst complex to just one ear, the forward fringe was about as helpful as
      when the stimuli were presented monotically, but the benefit of the backward
      fringe was substantially reduced. The backward-fringe advantage was restored by
      reducing the level, or delaying the onset, of the contralateral component of the
      fringe. The results suggest that the forward-fringe advantage is a robust
      phenomenon that is largely insensitive to input to the contralateral ear. In
      contrast, the backward-fringe advantage appears to be a fragile effect that can
      be affected by inputs from both ears.

PMID- 8132911
TI  - Detecting pitch-pulse asynchronies and differences in fundamental frequency.
AB  - A series of experiments investigated the detection of pitch-pulse asynchronies
      (PPAs) and of differences in fundamental frequency (delta F0's) between two
      simultaneous "formants," each of which consisted of a group of sinusoidal
      components spaced sufficiently closely in frequency to be incompletely resolved
      by the peripheral auditory system. For such stimuli, introducing a delta F0
      caused the pitch pulses of the two groups to become progressively more
      asynchronous at later and later parts of the stimulus. A comparison of the
      psychometric functions for the detection of delta F0's and of (constant) PPAs
      suggested that listeners could, under some circumstances, detect delta F0's from
      the resulting asynchrony. Using an adaptive procedure, it was also shown that,
      for a range of F0's from 20 to 125 Hz, the threshold PPA was constant at about
      2.5 ms. This relationship between PPA threshold and F0 differs from that
      previously reported for the detection of envelope asynchronies between pairs of
      sinusoidally modulated tones [e.g., Strickland et al., J. Acoust. Soc. Am. 86,
      2160-2166 (1989)], which remain constant in degrees, rather than in ms. Further
      experiments investigated the role of onset asynchronies in the detection of PPAs
      and showed that, although an asynchrony between the first pitch pulse in each
      formant was sufficient for near-asymptotic performance, listeners could still do
      the task when this cue was removed. For the detection of delta F0's, onset
      asynchronies also aided, but were not necessary for, discrimination.

PMID- 8132912
TI  - Gap detection and the precedence effect in young and old adults.
AB  - Thresholds for detecting a gap between two Gaussian-enveloped (standard deviation
      = 0.5 ms), 2-kHz tones were determined in young and old listeners. The gap
      detection thresholds of old adults were more variable and about twice as large as
      those obtained from young adults. Moreover, gap-detection thresholds were not
      correlated with audiometric thresholds in either group. Estimates of the width of
      the temporal window of young subjects, based on the detection of a gap between
      two tone pips, were smaller than those typically obtained when a relatively long
      duration pure tone is interrupted [Moore et al., J. Acoust. Soc. Am. 85, 1266
      1275 (1989)]. Because the amount of time it takes to recover from an adapting
      stimulus is likely to affect gap detection thresholds [Glasberg et al., J.
      Acoust. Soc. Am. 81, 1546-1556 (1987)], smaller estimates of temporal window size
      would be expected in this paradigm if the amount of adaptation produced by the
      first tone pip was negligible. The larger gap-detection thresholds of old
      subjects indicate that they may have larger temporal windows than young subjects.
      The lack of correlation between audiometric and gap-detection thresholds
      indicates that this loss of temporal acuity is not related to the degree of
      sensorineural hearing loss. In a second experiment on the precedence effect using
      the same subjects, a Gaussian-enveloped tone was presented over earphones to the
      left ear followed by the same tone pip presented to the right ear. To more
      realistically approximate a sound field situation, the tone pip presented to each
      ear was followed 0.6 ms later by an attenuated version presented to the
      contralateral ear. The delay between the left- and right-ear tone-pips was varied
      and the transition point between hearing a single tone on the left, and hearing
      two such sounds in close succession (one coming from the left and the other from
      the right) was determined. The transition point in this experiment did not differ
      between young and old subjects nor were these transition points correlated with
      gap-detection thresholds. These results indicate that monaural temporal acuity
      and binaural echo suppression may be based on different processes.

PMID- 8132913
TI  - Effects on sound localization of configuration and type of hearing impairment.
AB  - Localization ability of 87 bilaterally hearing-impaired listeners was tested in
      the horizontal and vertical planes, frontally and laterally. In those with
      sensorineural hearing loss, it was found that deficits in localization accuracy
      in different regions of auditory space could be related to different
      configurations of hearing loss. For example, there were associations between
      vertical plane discrimination and high-frequency sensitivity; and front-rear
      discrimination and mid-to-high-frequency sensitivity. These results agree with
      theoretical expectations, while the outcome overall contrasts with previous
      reports that localization performance is unrelated to audiometric configuration.
      A comparison of 13 listeners with conductive/mixed types of impairment with a
      sensorineural-loss group, matched for degree of loss, showed that a conductive
      component adds significantly to localization disturbance, particularly in the
      horizontal plane. The probable reason is a disturbance of low-frequency
      interaural time cues, and this occurs because a higher proportion of low
      frequency sound is likely to be transmitted via bone conduction relative to air
      conduction. Correlations between hearing loss and localization are only moderate,
      suggesting that aspects of hearing impairment, in addition to simple attenuation,
      may also reduce auditory localization performance.

PMID- 8132915
TI  - Nursing and AIDS.

PMID- 8132914
TI  - Who cares for the carers?

PMID- 8132916
TI  - Strain among nurses and their emotional reactions during 1 year of systematic
      clinical supervision combined with the implementation of individualized care in
      dementia nursing.
AB  - This study aimed at exploring nurses' views of the characteristics of severely
      demented patients, the difficulties these characteristics produced and the
      emotional reactions they evoked during the provision of care. Also, it aimed at
      exploring any changes in these aspects during a year of regular systematic
      clinical supervision combined with the implementation of individualized care at
      an experimental ward (EW) (n = 19) and at a control ward (CW) (n = 19). Data were
      collected by means of the Strain in Nursing Care scale, assessing the presence of
      certain characteristics in the patients, and how difficult each characteristic
      can be to handle. The Emotional Reactions in Nursing Care scale was also used,
      assessing 18 pairs of emotions. The analysis showed that agitation, not being
      responsive and unruly behaviour were the most common features while emptiness and
      agony turned out to be the most difficult problems to handle in the provision of
      care. Feelings of defeat and dissociation were reported to be almost as common as
      feelings of control and association. The EW nurses saw the patients as
      significantly more responsive, and victims of nihilation to a lesser degree and
      also patients' willfulness and emptiness was significantly easier to handle
      during the year of intervention. There were no significant changes on the CW. The
      mean values improved significantly in several aspects on the EW in comparison to
      the CW; patients seen as victims of nihilation, easier to handle agony,
      obediency, willfulness, evaluation and improved feelings of devotion and
      beneficence in the nurses. Thus the intervention seemed to improve the nurse
      patient relationship and to decrease the experience of strain in the nurses.

PMID- 8132917
TI  - The effects of student nurse community mental health placements on sufferers of
      mental health problems in the community.
AB  - The effects which student nurses have on the care of clients with mental health
      problems in the community is an area which has seldom been studied. With the
      closure of large psychiatric hospitals and the rise in community placements as
      part of Project 2000, an increasing number of students are being placed in the
      community. The study gathers data from clients attending five self-help/support
      groups in the North Derbyshire area of England. Analysis of the data challenges
      assumptions generally held by community psychiatric nurses (CPNs) that the
      presence of a third person, e.g. student/visitor, during a CPN home visit to the
      client is detrimental to the therapeutic interaction between the CPN and the
      client. The findings are inconclusive but suggest that some client groups
      (possibly those with long-term mental health problems) may find the presence of a
      student during a CPN visit facilitative. The study raises the issue of the
      student nurse/patient power relationship within a support group. Findings suggest
      that membership of a support group is empowering to the client and illustrates
      that clients in the community have greater control over the involvement of
      student nurses in their care than patients in hospital. Groups within the sample
      expressed a unanimous view that student nurse placements should be long enough to
      allow therapeutic nurse/client relationships to develop. This is in direct
      contrast to the current Project 2000 Common Foundation Programme approach of
      short observational non-institutional placements.

PMID- 8132918
TI  - Relatives' support groups in a special hospital: an evaluation study.
AB  - A support group for the relatives and friends of patients at a special hospital
      in Merseyside, England, has been in operation for over 1 year. A detailed
      evaluation of that group has been completed based on the minutes of each meeting
      and on a structured questionnaire sent out to each relative/friend involved. The
      evaluation provides an illuminating account of the particular needs of this
      group, highlighting many of the concerns expressed by the Committee of Inquiry
      during the recent Public Inquiry at Ashworth Hospital. The results of the
      evaluation are discussed in relation to work already completed on network support
      and mental health, as well as the recent work involving the relatives of patients
      in the community. It provides a direction for future work and research within the
      special hospitals.

PMID- 8132919
TI  - Nursing dementing elderly people: ethical issues.
AB  - It has been estimated that up to 40% of people with moderate to severe dementia
      live in residential homes or long-stay hospital wards. This paper examines some
      of the ethical issues that arise in nursing people suffering from dementia within
      an institutional setting. The paper focuses first on the nursing profession and
      the recently published Strategy for Nursing. The fundamental patient/client
      values within the strategy recognize the uniqueness of the individual and the
      importance of providing nursing care which is tailored to meet individual needs.
      The next part of the paper will examine the difficulties associated with
      individualizing care for people suffering from dementia and highlight some of the
      ethical issues involved in looking after them. Finally, some of the general
      professional issues involved are examined and some tentative suggestions are put
      forward as to how some of the identified problems might be tackled.

PMID- 8132920
TI  - Predicting which patient will fall again ... and again.
AB  - In order to compare the characteristics, preventive interventions and outcomes of
      single and multiple fallers, a retrospective cross-sectional study was conducted
      in a 680-bed acute-care hospital in Western Australia. Fifty patients falling
      more than once (multiple fallers) were randomly selected from all patients
      reported to have fallen between 1 July 1989 and 31 December 1989, and age-sex
      matched with 50 patients falling once in the trial period (single fallers). In
      total, 382 in-patients were reported to have sustained 578 falls in the 6-month
      trial period. Fifty-two per cent of these falls involved multiple fallers. An
      analysis of the 100 single and multiple fallers showed that single fallers were
      more likely to have fallen from their bed; be discharged home from hospital; and
      be clinically deteriorating at the time of the fall. Multiple fallers were more
      likely to be transferred to a long-term nursing facility after discharge from
      hospital; suffer blindness/poor vision; be sedated post fall; be ordered to be
      restrained following a fall; and be hospitalized for longer periods. There was
      also a tendency for multiple fallers to repeat the type and location of the fall
      on successive falls. Stepwise logistic regression showed that falling from the
      bed on the first fall predicted remaining a single faller. Being ordered to be
      restrained following the first fall and hospitalized for longer periods predicted
      the patient would fall repeatedly. Further analytical research incorporating an
      expanded number of independent variables is needed to allow confident assertions
      of causality. To test the effectiveness of preventive measures, a prospective
      longitudinal study is required.

PMID- 8132921
TI  - Developing trusting, caring relationships: home care nurses and elderly clients.
AB  - Trusting as an area of research has not been critically examined in nursing
      research literature. In this study, nurses working in home care and elderly
      clients were interviewed to ascertain the process of developing a trusting
      relationship. Data were obtained from seven home care nurses and six elderly
      clients who were interviewed from one to three times. The data were analysed
      using grounded theory methodology and sorted using Microsoft Word software on a
      Macintosh computer. The core category which was identified in the data was
      labelled 'trusting, caring relationships'. This core category encompassed
      trusting which is developed and the caring which the nurses provide. Home care
      nurses and elderly clients moved through four phases: initial trusting;
      connecting; negotiating; and helping. The findings have implications for novice
      nurses working with elderly people, as well as for programme development and
      education. More research needs to be done on trust in different contexts to
      assist all nurses in establishing nurse-client relationships.

PMID- 8132922
TI  - Defining and assessing risky behaviours.
AB  - This paper presents the deliberations and conclusions of an international group
      of health practitioners, researchers and planners who met in 1991 to explore
      risky behaviours and risk assessment in the context of the World Health
      Organization's strategy Health for All By 2000. A definition of risky behaviours
      is discussed and a method of exploring risk contexts, 'a risk equation', is
      presented. Lay risk assessment is explored and contrasted with professional
      perceptions of risk as evidenced in health education campaigns. It is concluded
      that the application of epidemiological techniques--the study of the incidence
      and prevalence of risk-related and health-related behaviours--employing
      qualitative methods provides a useful means of exploring the social and cultural
      context of risk behaviour.

PMID- 8132923
TI  - A critical analysis of Neuman's systems model in relation to public health
      nursing.
AB  - The public health movement is an old discipline being given new life and meaning
      based on a recognition of continuing health problems associated with social
      inequalities. The 'new public health' movement has goals which are closely
      aligned to those of the World Health Organization in their Health for All by 2000
      initiative which represent a collective approach to health in contrast to the
      current political emphasis on individual responsibility for health. Public health
      nursing is a relatively new concept in Britain but posts are beginning to be
      established in many areas where nurses are working in partnership with
      communities in a public health capacity. At a time when this area of nursing is
      in its relative infancy it is appropriate to develop a clear philosophy and
      framework and to examine potential strategies. This paper sets out to contribute
      to the development of this discipline by critically analysing the work of Betty
      Neuman to determine its utility for public health nursing.

PMID- 8132924
TI  - The effects of comprehensive guidelines for the care of sickle-cell patients in
      crisis on the nurses' knowledge base and job satisfaction for care given.
AB  - The primary purpose of this study was to determine the effects of comprehensive
      nursing guidelines for sickle-cell patients in crisis on the nurses' knowledge
      base and job satisfaction for nursing care given. This study was carried out
      through the use of a single-group pretest-posttest design. A total of 18 subjects
      participated in the study. At the pretesting, each subject completed an
      Individual Information Questionnaire for the collection of background data, a
      Knowledge Base tool and a Job Satisfaction tool. Afterwards, all subjects
      attended 10.5 hours of educational programmes on sickle-cell disease, treatment,
      interventions and relaxation training. Following this, the comprehensive
      guidelines for the care of sickle-cell patients were instituted. At 3 months and
      6 months after the guidelines had been in effect, subjects were again asked to
      complete the Knowledge Base and Job Satisfaction tools. The results of the tools
      were then measured comparing the three time intervals for any differences in
      knowledge and job satisfaction using independent measure t-tests. t-Tests were
      also performed for each question on the Job Satisfaction tool comparing the three
      time intervals. The results of the analyses demonstrated that there was a
      statistically significant increase in knowledge between the pretest and 6 month
      time interval. The findings also showed that there was no statistically
      significant increase in overall job satisfaction. However, the t-test results
      from the individual questions demonstrated a statistically significant increase
      in job satisfaction in the areas of nurse/physician collaboration and having a
      broad knowledge base of sickle-cell disease.

PMID- 8132926
TI  - The intake of nutrients by hospitalized pensioners with chronic wounds.
AB  - Three issues concerning nutrition in hospital are frequently highlighted in
      nursing literature: the risk of elderly patients becoming malnourished, the lack
      of adequate nutritional care provided by nurses and the importance of certain
      nutrients in the process of wound healing. This detailed study of seven subjects
      on care of the elderly wards examined their intake of certain important
      nutrients. The findings are discussed in relation to the Department of Health's
      Estimated Average Requirements (1991) and the achievement of an optimum wound
      healing environment. The results add further to the evidence that many patients
      do not consume sufficient levels of nutrients and in some cases did not even
      receive adequate quantities of these nutrients on their plates. Nurses'
      nutritional care was limited in most cases and no subjects received an optimum
      nutritional environment for wound healing.

PMID- 8132925
TI  - The conceptual validity of a taxonomy of nursing interventions.
AB  - The purpose of this paper is to report validity evidence for the nursing
      intervention taxonomy developed as part of the Nursing Intervention Lexicon and
      Taxonomy (NILT) Study. Using eclectic classification methods of library science,
      cognitive science, nursing science and computational linguistics, a taxonomy of
      nursing interventions consisting of seven categories was developed. These
      categories which incorporate care as a central concept are described and defined,
      and prototypical examples of each category are presented. Brinberg & McGrath's
      validity schema provides the framework within which evidence for validity as
      value, validity as correspondence and validity as generalizability were examined.
      Comparison of the NILT categories with previously published categorizations of
      nursing functions and interventions provides strong support for the validity of
      this classification. Additionally, comparison of the NILT categories with two
      internationally derived categorizations of nursing functions supports the
      robustness or generalizability of the NILT classification.

PMID- 8132927
TI  - A therapeutic group for clients with acute mental health problems.
AB  - A therapeutic group for clients with acute mental health problems is described
      using a case study research design. The setting of the group is a British
      community mental health centre. Theoretical and research approaches to brief
      therapeutic work with clients are discussed. Results include qualitative
      descriptions of the group from the perspective of various respondents and
      quantitative descriptions of client attendance. The group was evaluated
      positively by respondents and high attendance rates indicated that the group met
      clients' needs. The group was primarily utilized by professionals as an addition
      to present services rather than as an alternative to in-patient hospitalization.
      However, in practice many of the clients needed some degree of professional
      support after ceasing to attend the group. In this study, the establishment of a
      therapeutic group for clients with acute mental health problems improved inter
      professional relations. The ability to facilitate therapeutic groups is an
      important competence for mental health nurses.

PMID- 8132928
TI  - Water intoxication: one nursing staff's response and intervention.
AB  - Water intoxication is a significant problem for psychiatric nurses, especially
      those in long-term care settings. Water intoxication can cause psychological and
      physiological symptoms which can lead to death. The programme described in the
      paper can significantly modify and change patient behaviour and assist patients
      in controlling their own impulses to participate in self-limiting fluid and their
      own self-care satisfactorily.

PMID- 8132929
TI  - Focus groups in distance nursing education.
AB  - This paper describes an educator's experience using focus groups with post-RN
      nursing students in a course offered by audio teleconferencing. The purposes of
      implementing focus groups included: to increase involvement of students located
      in the distance education settings, to implement principles of adult learning, to
      increase opportunities for drawing on the experience of the students, and to
      improve the quality of learning experience offered by distance education. An
      example is given to demonstrate how the process was used to integrate the focus
      group experience into the distance education classroom.

PMID- 8132930
TI  - The use of focus groups in a study of attitudes to student nurse assessment.
AB  - This paper describes the use of focus groups in the first phase of a study to
      investigate the attitudes of teachers and clinical assessors to the assessment of
      student nurses. It offers a description of the methodology, with an analysis of
      its strengths and weaknesses.

PMID- 8132931
TI  - Boundary work in the nursing curriculum: the case of sociology.
AB  - A discussion of the boundaries between nursing and sociology is contained in this
      paper. The creation of nursing as an academic subject is discussed and compared
      with the creation of academic geography. The creation of academic subject
      involves 'boundary work' in which power and legitimacy are conferred on some
      forms of knowledge and not others. Boundary work enables a discipline to stake
      out a claim to its legitimate territory and the resources that go with it. In a
      practice discipline such as nursing, the boundaries between nursing and
      supporting subjects, such as sociology and physiology, create problems of
      transfer of learning. This has implications for curriculum design. Bernstein's
      work on educational transmissions offers useful insights. He suggests a
      distinction between educational knowledge codes. 'Collection' codes involve
      strong boundaries between subjects, 'integrated' codes imply weak boundaries. The
      implications of the move to an integrated code in nursing are discussed. The
      existence of an integrated code implies a 'strong ideological consensus' within a
      discipline. In nursing this entails a belief in the 'individualized care' of the
      patients. This is incompatible with the sociological understanding of nursing.

PMID- 8132932
TI  - Some considerations concerning practice and feedback in nursing education.
AB  - Dominant approaches to reflective practice and experiential learning in Australia
      and the United Kingdom seem to reflect a limited view of the functions of
      practice and feedback in human learning. These functions will be described from a
      cognitive psychological perspective and the weaknesses of such approaches
      discussed. It will be argued that Schonian reflective practice and some
      experiential learning techniques can reinforce rather than eliminate
      inappropriate action tendencies and that this, in turn, could consolidate
      nursing's theory-practice gap.

PMID- 8132933
TI  - Underpinnings of ethical reasoning in nursing.
AB  - Nursing is a manifestation of a value according to which it is morally good to
      promote physical and psychological well-being. Such a moral obligation involves
      making judgements. Ethical judgements are the decisions a person makes on whether
      a particular act is right or wrong. Ethical principles serve as the basis for
      ethical rules and as a framework for decision-making. Ethical theory provides a
      rationale that explains the principles and rules in order to provide a structured
      approach to ethical reasoning. Although ethics is not a science with verifiable
      answers, a knowledge of ethical theory enables nurses to make decisions in a
      manner that is more comprehensive and well reasoned than is opinion or intuition.
      In this paper, an overview of ethical theories, ethical principles and influences
      on ethical or moral reasoning is presented as well as the ethical decision-making
      process.

PMID- 8132934
TI  - Intensive care: situations of ethical difficulty.
AB  - Twenty enrolled nurses (ENs), 20 registered nurses (RNs) and 20 physicians
      working in intensive care in northern Sweden narrated 255 stories about their
      experience of being in ethically difficult care situations. The ENs' stories
      mainly concerned problems relating to relationship ethics, the stories narrated
      by the physicians mainly concerned problems relating to action ethics, while the
      RNs' stories gave equal attention to both kinds of problems. The most common
      theme of both the RNs' and the physicians' stories was that of too much
      treatment. An obvious similarity between the ENs, RNs and physicians was that
      they saw themselves as equally lacking in influence in ethically difficult care
      situations. The only apparent difference between the three groups, however, was
      that the ENs brought up relationship problems more often than the others. Thus,
      the differences between the RNs and the physicians were fewer than usually
      reported in the literature. This might be related to the specialization of
      intensive care.

PMID- 8132935
TI  - Critical incident technique: a clarification.

PMID- 8132936
TI  - Student healthcare delivery and financing programs: adapting to healthcare
      reform.
AB  - College health professionals want to assure the unique healthcare and health
      education needs of college students will continue to be met under national and
      state healthcare reform. This may be an "all or nothing" proposition. Either
      colleges and universities will have exclusive control of healthcare delivery for
      the college student population or else college health will not be a major force
      in healthcare reform. If college health is to play a meaningful role in future
      government-controlled health insurance programs, it must first demonstrate that
      current health services and insurance financing programs meet minimum quality
      standards. This proposal calls for expanding existing federal laws to create
      qualified student health plans and integrating the college health model into a
      reform package based on employer-sponsored health insurance. The concept of
      qualified student health plans allows for a high degree of flexibility that can
      be integrated into the majority of state and federal healthcare reform proposals,
      including the plan proposed by President Clinton, that are not based on a single
      payer system. Ultimately, the authors suggest, their proposed plan would
      eliminate the current situation, in which large numbers of college students are
      uninsured or underinsured.

PMID- 8132937
TI  - Suicide attempts and threats on one college campus: policy and practice.
AB  - Because of a university policy requiring a mental health evaluation of every
      student who is cause for worry with respect to his or her own safety, the
      counseling center at the College of William and Mary has been able to examine
      almost all situations in which students are suicidal or thought to be suicidal.
      Over the course of 1 calendar year, counseling center clinicians recorded data on
      every case of students who attempted or threatened suicide or were otherwise of
      concern to residence life staff or faculty or administrators because of a
      perceived potential for suicidality. Sixty such situations, including 11 suicide
      attempts and 14 threats, arose. No completed suicides were recorded. The rate of
      suicide attempts was 14.5 per 10,000 students, and the rate of suicide threats
      was 18.4 per 10,000 students, a total of 32.9 cases per 10,000 students. Findings
      by race, gender, and class are outlined, although low base rates did not yield
      adequate statistical power to make comparisons practical within these groupings.
      The most prevalent risk factor found in suicide attempters was work or school
      failure; for suicide threateners, it was difficulty in a relationship; and for
      those found to be nonsuicidal, the major problem was social isolation. Follow-up
      therapy was the most frequently used intervention for attempts and threats,
      whereas instructions for using the emergency on-call system was the most used
      option in the otherwise worrisome cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132938
TI  - Very brief psychological interventions with university students.
AB  - Annual college mental health service statistics reveal that 50% to 60% of all
      students served are seen for very brief psychological interventions--5 or fewer
      sessions. A substantial portion of the students benefit from these very brief
      contacts. The authors review the selection criteria for student and therapist
      that make very brief intervention possible. The student must be motivated for and
      seek a brief encounter and must enter the therapeutic relationship with the
      capacity for trust already in place and the professional qualifications of the
      therapist already established. The problem presented should be sufficiently clear
      and manageable to be resolved, or to begin being resolved, in a few sessions.
      Finally, the student must have the capacity for rapid insight and learning. The
      therapist brings to the relationship a belief in the value of very limited
      sessions, the capacity to develop a positive relationship quickly, and the
      ability to determine when it is appropriate to work in such a short time frame
      and to use the time most effectively. Four ways that students may benefit from
      very brief psychological interventions include (1) psychodynamic therapy, (2)
      crisis intervention, (3) mental health consultation, and (4) managed referral.
      Case illustrations and clinical methods are presented.

PMID- 8132939
TI  - Did an AIDS peer education program change first-year college students' behaviors?
AB  - Students who have attended the AIDS peer education program (APEP) at Florida
      Atlantic University have consistently evaluated it in an overwhelmingly positive
      manner. This has inspired the university staff to move on to another issue of
      concern: Is attendance at such a peer education program associated with HIV
      related changes in behavior? To answer this question, the authors surveyed a
      random sample of first-year students by mail at the beginning and end of the
      1991/92 school year. In the interim, some students participated in an APEP and
      some did not--resulting in a before-after design. Those who attended an APEP
      reported they were more likely than nonattendees to engage in behaviors that were
      aimed at preventing HIV infection. The validity problems inherent in self
      selecting attendance and in surveying by mail, especially in regard to causation
      versus association, lead us to attempt a face-to-face interview design in future
      evaluations. With stricter control over other potential intervening variables, we
      may be more likely to obtain data that relate change in behavior to the APEP.

PMID- 8132940
TI  - Dimensions of self-efficacy among three distinct groups of condom users.
AB  - Condom use self-efficacy can be defined as expectations about one's ability to
      use condoms under a variety of circumstances. This investigation examined the
      factor structure of the Condom Use Self-Efficacy Scale (CUSES) in an 18- to 23
      year-old college population (N = 339) and tested the ability of the factors to
      distinguish among three groups of condom users (nonusers, sporadic users, and
      ritualistic users). Emerging from a principal components analysis were four
      reliable factors labeled Mechanics, Partner's Disapproval, Assertive, and
      Intoxicants. Results from a discriminant analysis indicated that sporadic users
      were best distinguished from ritualistic users by number of sex partners, use of
      intoxicants, and intensity of alcohol use. The sporadic users had more sex
      partners, were less confident of their ability to use condoms when intoxicated,
      and were heavier drinkers than were the ritualistic users. Nonusers were best
      distinguished from ritualistic users by the factor labeled Assertive. Nonusers
      were significantly less confident in their ability to discuss condoms and to
      insist on their use with a sexual partner. Implications of the findings for
      improving campus-based programs to prevent the spread of human immunodeficiency
      virus infection and sexually transmitted diseases are discussed.

PMID- 8132941
TI  - Nursing diagnosis as a framework for college health nursing protocols.
AB  - Standardized nursing protocols in college health must facilitate cost-effective
      student healthcare, allow nurses to function within the legislated scope of
      practice of their state, and still address the health needs of the patient
      population. Nursing diagnosis provides the framework for a protocol model that
      does all of this, as well as providing professional growth opportunities for
      college health nurses and nursing.

PMID- 8132942
TI  - On protocols for advanced practice nurses.

PMID- 8132943
TI  - A rape awareness and prevention model for male athletes.

PMID- 8132944
TI  - Date rape: politics or pragmatism?

PMID- 8132945
TI  - Codependence issues and the college health nurse.

PMID- 8132947
TI  - Optometric care of older patients: interaction of the visual and physical
      environments.

PMID- 8132946
TI  - "Vision through my aging eyes" revisited by design.

PMID- 8132948
TI  - Pesticide labels: proven protection or superficial safety?
AB  - BACKGROUND: The readability of restricted-use pesticide labels is an important
      element in preventing misuse and unsafe application practices. METHODS: An
      optometric analysis of 54 pesticide labels was conducted to determine the visual
      acuity required to read the average general use label. Additionally, a survey of
      1623 Wyoming residents was conducted to determine the extent label directions are
      read, understood, and adhered to. RESULTS: A visual acuity of 20/30 and 20/40 is
      required to read the average general use and restricted use pesticide label,
      respectively. The mean and mode cognitive reading level required is the 11th
      grade. About half of the sample population read the label and two thirds reported
      always following label directions. CONCLUSIONS: A significant proportion of the
      American public can not or does not read or understand pesticide labels and does
      not follow the label instructions. Essential pesticide use and safety information
      is not being effectively communicated to the public.

PMID- 8132949
TI  - Visual disorders associated with Alzheimer's disease and optometric management.
AB  - BACKGROUND: Patients with early or undiagnosed Alzheimer's disease commonly
      experience visual disorders that may cause them to seek optometric evaluation.
      METHODS: As this condition is difficult to diagnose, clinicians may be faced with
      a confusing presentation of symptoms. Typically, visual perceptual disorders
      exist in the absence of abnormal ocular findings. RESULTS: Familiarity with the
      visual disorders associated with Alzheimer's disease and recognition of the value
      of neuropsychological evaluation are critical to accurate diagnosis and
      management. CONCLUSIONS: Case presentations are used to illustrate these issues.

PMID- 8132950
TI  - The ability of the geriatric population to read labels on over-the-counter
      medication containers.
AB  - BACKGROUND: A Senior Assembly Proposal was presented to the California Assembly
      calling for a change in over-the-counter (OTC) medication labeling to make the
      print more readable. It proposes that a panel of optometrists and
      ophthalmologists be created to define "readable" print. This proposal came about
      because a large segment of the 60 years and older population is unable to read
      the printed material on OTC medication labels. METHODS: This study investigated
      the effects of vertical letter height and horizontal letter compression on
      readability. Three labels with lettering of different size and compression were
      used. RESULTS AND CONCLUSIONS: It was found that letter compression significantly
      affected readability while letter height was less of a factor. Results of this
      study suggest that the lettering on OTC medication labels should be at least
      1.2mm in vertical height, or 20/40 Reduced Snellen (RS) visual acuity level, and
      should have no more than 40 characters per inch.

PMID- 8132951
TI  - The nursing home comprehensive eye examination.
AB  - BACKGROUND: There is significant need for optometric care in long-term care
      facilities which can be expected to increase in the next decade. METHODS: The
      previous ophthalmic and medical literature was reviewed and the practical aspects
      of providing eye care in a nursing home were analyzed. RESULTS: Comprehensive
      nursing home care requires the integration of portable ophthalmic equipment, a
      modification of standard testing procedures, clear and concise documentation, and
      close communication with other health care providers on the nursing home clinical
      staff. CONCLUSION: Optometrists must consider the incorporation of nursing home
      care into their clinical practice, while recognizing the unique aspects of
      providing eye care within a long-term care facility.

PMID- 8132952
TI  - Clinical pearls in optometric management of the geriatric patient.
AB  - BACKGROUND: Painstaking attention to detail is absolutely necessary for
      optometrists to provide the appropriate clinical management of the geriatric
      patient. METHODS: Clinical management techniques (pearls) are discussed which aid
      in the diagnosis and treatment of problems specific to geriatric patients.
      Factors noted in patient presentation are stressed and include physical
      appearance, ability to move about, and use of other senses. The most commonly
      occurring eye anomalies occurring in the geriatric population are discussed
      including iatrogenic drug side effects, pupillary anomalies, extraocular palsies,
      dry eye, corneal degenerations, refractive error changes, lenticular changes,
      glaucoma, age-related maculopathy, vitreoretinal disease, and ocular
      manifestations of systemic disease (vascular occlusive disease, diabetes,
      ischemic optic neuropathy, other neuro-ophthalmic disease). RESULTS: Conditions
      relatively rare in the young population occur with regularity in the elderly
      population and often must be assumed to be present in concert with some typical
      patient presentations in the geriatric population. CONCLUSIONS: Optometrists as
      primary health care providers often provide the only avenue individuals with
      blinding and sometimes life threatening conditions have in managing these
      conditions. Optometrists managing geriatric patients are required to know what
      happens to this population from an ocular disease as well as other function and
      dysfunction standpoint.

PMID- 8132953
TI  - Essential lessons of gerontology and geriatrics.
AB  - BACKGROUND: As clinicians, adult children of aging parents, taxpayers, and future
      retirees, optometrists have multiple reasons for wanting to know more about aging
      and for wanting to communicate better with older people. METHODS: Fundamental
      principles emerging from gerontological and geriatrics research are reviewed.
      Suggestions are offered for improving clinical approaches and practice settings.
      RESULTS: Population heterogeneity is the rule with aging due to sociocultural as
      well as biophysiological changes. Follow through with treatment regimens depends
      on the availability of financial and human resources and on what else is going on
      with the older patient at the time. CONCLUSIONS: Diseases should be treated at
      all ages. Particular attention should be devoted to medications management, to
      compensating environmentally for normal age changes in sensory functioning, and
      to avoiding iatrogenic consequences of treatment.

PMID- 8132954
TI  - The demographic, social, and conceptual contexts of aging and vision loss.
AB  - BACKGROUND: Age-related changes to the eye and functional implications of vision
      loss are well-known. However, these changes occur in the context of broad
      demographic and social changes. METHODS: The structural demographic changes in
      the United States, the social context of vision and aging, and the conceptual
      model of disablement are reviewed. RESULTS: The International Classification of
      Impairments, Disabilities, and Handicaps (ICIDH) was published by the World
      Health Organization (WHO) in 1980, and may serve as a model for our better
      understanding of how the structural demographic changes, the social context of
      vision and aging, and the conceptual model of disablement are affecting public
      policy in eye and vision care. CONCLUSIONS: At present, there is no comprehensive
      national policy that addresses the eye and visual rehabilitation of older persons
      who have lost vision. Defining a conceptual context may help us develop public
      policy to meet the demands of the aforementioned social and demographic changes.

PMID- 8132955
TI  - 6 x 1 = 1: Part IV.

PMID- 8132956
TI  - [Breast reconstruction with inferior transverse abdominal flap after mastectomy
      for cancer].
AB  - Breast reconstruction with an inferior transversal abdominal flap provides good
      quality cosmetic results. Indications for this flap technique are presently
      limited because of the frequency of complications in early series. The aim of
      this study was to evaluate the different parameters which could reduce the number
      of complications. From January 1989 to July 1991, 25 patients were treated with
      this method at the Rene-Gauducheau Centre. All patients were treated with the
      same surgical technique. Based on the complications observed in this series and a
      review of the literature, we were able to determine those factors which could
      limit the number of complications. Preoperative patient selection defined a
      population at risk of vascular complications. This population corresponded to a
      good indication for double pediculated flaps. Global flap removal, the muscle and
      the anterior sheath of the aponevrose together, and maintaining the patient in a
      sitting position for five days after the operation helped reduce the frequency of
      complications. Folding the abdominal wall with a nonabsorbable sheath appeared to
      be a simple and reliable method of reducing the number of abdominal
      complications. The double pediculated flap was indicated in all cases at risk of
      partial necrosis or when a large volume was necessary to avoid asymmetry. Using
      this type of management, breast reconstruction with inferior transversal
      abdominal flap is the first intention technique used at the Rene-Gauducheau
      Centre in Nantes.

PMID- 8132957
TI  - [Laparoscopic surgical excision of adnexal cysts. Methods and indications in a
      series of 70 patients].
AB  - Surgical coelioscopy has become a regularly used technique for the treatment of
      benign cysts of the annexes. Complete exeresis and certain histological diagnosis
      are assured and the postoperative period is simpler than after laparotomy. The
      risk of pelvic adherences is reduced. We performed coeliosurgery via the
      transparietal or intraperitonial method in a series of 70 patients for 85
      resections of cysts, ovaries or annexes. Length of hospitalization was short and
      complications were rare. Despite convincing clinical explorations including
      echography and coelioscopy, we observed one border line tumour and one stage I
      serous cystadenocarcinoma at histological examination after coeliosurgery. The
      two observations led us to question percoelioscopic treatment cysts of the
      annexes but also emphasize the need for careful preoperative work-up and
      peroperative technique. The indication for laparotomy should be seriously
      considered in doubtful cases.

PMID- 8132958
TI  - [Evaluation of second look laparotomy in the management of epithelial ovarian
      tumors. 88 interventions performed at the Dijon CAC between 1979 and 1990].
AB  - OBJECTIVE: To evaluate the second look laparotomy in the treatment and management
      of epithelial ovarian carcinoma. DESIGN: A retrospective study (1979-1990).
      SETTING: Centre G.-F. Leclerc, Dijon. SUBJECTS: 88 patients underwent a 2e look
      laparotomy during the period. Most of them (69.3%) were stage III or IV cancers.
      RESULTS: The predictive value of a negative second look is of evidence: 5 years
      survival of 63% versus 4% if residual tumor is observed. Nevertheless the
      therapeutic value of a tumoral exenteration during the second look is not
      demonstrated: the 5 years survival is only of 7% for these patients. CONCLUSIONS:
      This study demonstrates the importance of an appropriate surgery during the first
      look in the management of ovarian tumors. The contribution of the second look is
      primarily a prognostical contribution.

PMID- 8132959
TI  - [A difficult diagnosis: pelvic-abdominal actinomycosis abscess].
AB  - A laparotomy for hysterectomy was performed in a 46-year-old nulliparous woman
      who had worn an intra-uterine sterilization device for 8 years. The patient was
      in poor general health and had had abdominal pain and repeated episodes of fever
      over the preceding 3 months. An abscess of the abdominal muscle was found
      peroperatively. No perforations of the small or large intestine were observed.
      The pathology examination yielded the diagnosis of Actinomycosis. Actinomyces
      israeli is the most frequency observed Actinomycae in humans. It is a saprophyte
      organism of the intestinal flora, not usually found in the vagina and observed in
      3.5% of cervical swabs of patients wearing an intra-uterine device (Gupta
      bodies). The frequency increases with the duration of insertion and the
      pathogenicity appears when the immune responses are deficient and/or when a
      cofactor is involved. Treatment relies on surgical exeresis and prolonged
      antibiotics (penicillin G or macrolides). Hyperbar treatment is sometimes used.

PMID- 8132960
TI  - [Tubal bilharziasis].
AB  - We report a case of tubular bilharziosis discovered on a surgical specimen after
      salpingectomy. Tubular bilharziosis is not exceptional in endemic zones but is
      rarely found in Europe. The species most often isolated is Schistosoma
      haematobium. Contamination occurs via vascular anastomoses between the bladder
      and the genital organs. Bilharziosis has been shown to be a cause of extra
      uterine pregnancy although its effect on fertility is yet to be established.

PMID- 8132961
TI  - [Chorionic villus needle sampling by the transabdominal route or by placental
      centesis. A series of 930 cases].
AB  - The authors report on a series of 930 chorion villus sampling diagnoses made with
      a needle by the transabdominal route, from January 1991 to October 1992 at the
      Prenatal Diagnosis Center in Marseille. Indications for prenatal diagnosis were:
      raised maternal age in 75% of cases (N:698); ultrasound findings in 11% (N:106),
      chromosome abnormalities in the family in 6% cases (N:53), raised human chorionic
      gonadotrophin in 4% cases (N:38), parental rearrangement in 2% cases (N:20), and
      sex linked disease in 1% (N:15). The success rate was 97% with 29 failures; the
      number of needle insertions was one in 97% cases and two in 3% cases. The average
      gestational age at sampling was related to the indications; 16 weeks of
      amenorrhoea for raised maternal age, and 22 weeks of amenorrhoea for ultrasound
      findings. Thirty one abnormalities were observed, four balanced translocations,
      and seven placental mosaicisms. Forty eight pregnancies terminated in abortion.
      The rate of fetal loss was 3.5% (7 cases) for the 200 first cases and 1% (8
      cases) for the 730 following cases. Choriocentesis through the transabdominal
      route provides a diagnosis within a few days and the rate of fetal loss is close
      to that of amniocentesis. These arguments are in favour of an extension of this
      method of sampling.

PMID- 8132962
TI  - [Study of the reasons for therapeutic abortions, stillbirth and neonatal
      mortality in the Brittany region in 1991].
AB  - The reasons for 186 medically indicated terminations of pregnancy, 178
      stillbirths, and 126 neo-natal deaths were analysed by a multi-disciplinary team
      after a thorough enquiry into the social and medical context for the deaths or
      for the decision to interrupt the pregnancies. This was undertaken on the
      initiative of the regional technical consultative commission for enquiring into
      births, and according to a protocol that had already been partly used by a group
      studying the neonatal period in Ille and Vilaine. A comparison of the causes
      according to the type of death shows the value of following up these three
      indicators to the plan and appropriate policy for three weeks following delivery.
      A certain number of questions about definitions and classifications still have
      arisen.

PMID- 8132963
TI  - [Refinement of a new Doppler sensor for studying fetal hemodynamic disorders
      (animal model)].
AB  - Fetal Doppler techniques applied in the human have furnished information of the
      regional haemodynamics of fetal circulation but has in general been associated
      with haemodynamic data obtained by vessel puncture, i.e. arterial pressure or
      blood gases. With animal models, further data can be obtained in the course of
      induced pathologies or during dynamic test (hypoxia, drugs). Several studies on
      utero-placental haemodynamics have been conducted using electromagnetic sensors
      and implanted catheters. This type of technique is only possible for certain
      vessels (usually the cord vessels) and, for example, cannot be used to
      investigate the cerebral area. The aim of this work was to develop a Doppler
      sensor which could be implanted in utero on the fetus and would permit a real
      time measurement of the major fetal blood flows. The sensor was made of 2
      continuous Doppler transducers (13 mm x 4 mm) with a 45 degrees inclinasion to
      the sensor surface and carried on a parallellopipedic support system measuring 20
      mm x 6 mm. The active surface of the transducer has a silicone film covering. The
      sensor is placed on the skin of the fetus, facing the artery to be explored, and
      oriented towards capture of a quality signal. The sensor is then sutured to the
      skin and the coaxial leads of the 2 transducers are exposed through the skin of a
      pregnant ewe. The leads are connected to a Doppler control panel later after the
      operative period. Three sensors can be implanted simultaneously to monitor
      umbilical, cerebral and uterine blood flows.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8132964
TI  - [Weak transplacental passage of prazosin (Alpress) during the third trimester of
      pregnancy. 3 cases].
AB  - Prazosin is a selective peripheral alpha 1-adrenoceptor antagonist used in the
      treatment of hypertension and heart failure. This drug has the disadvantage of
      relatively short terminal half-life (of the order of 2 to 3 hours); its wide use
      has been limited by the number of daily administrations. Recently, a new
      formulation of prazosin has been commercialized i.e., prazosin-gastrointestinal
      therapeutic system (P-GITS) given once daily in doses of either 2.5 or 5.0 mg
      (i.e., Alpress). The potential suitability of this controlled-release system as
      treatment of hypertension during pregnancy seems important. However, the possible
      transplacental passage of PRZ was unknown. We aimed to study this phenomenon in
      three pregnant women given a once daily 5 mg dose of P-GITS during the third
      trimester of pregnancy. There is a slight transplancental passage of prazosin
      i.e., of the order of 10 to 20% of the maternal concentration level determined at
      the same time. Concerning neonatal outcome, no problems were noted and the babies
      left the hospital in good health. Prazosin-GITS offers a new approach to control
      and improve the outcome of hypertensive therapy during pregnancy.

PMID- 8132965
TI  - [Spontaneous unilateral adrenal gland hemorrhage and pregnancy].
AB  - Spontaneous unilateral haemorrhage of the adrenal gland during the third
      trimester of pregnancy is a rare event. The diagnosis may be suspected on the
      basis of echographic or MRI explorations. There is no sign of endocrine
      dysfunction. The pregnancy may be conducted to term when the diagnosis is
      probable but echographic monitoring shows the absence of further development.
      Only one analogous observation based on MRI diagnosis was found in the
      literature.

PMID- 8132967
TI  - [Spontaneous migration of a tubal ligation clip via the inguinal canal. An
      exceptional complication of tubal sterilization].

PMID- 8132966
TI  - [Acute adrenal gland decompensation in the immediate postpartum].
AB  - We report the case of acute adrenal gland failure which occurred one hour after
      cesarian section for the delivery of a child after 31 weeks of amenorrhoea. The
      clinical picture of the mother was immediately severe and was dominated by
      neurological features: profound coma with a bilateral Babinski's sign. The
      laboratory tests however only revealed severe hypoglycaemia among the classical
      signs of adrenal gland failure. It was extremely difficult to correct the blood
      glucose level without concomitant administration of corticosteroids.

PMID- 8132968
TI  - Diploid Paragonimus westermani: the experimental completion of its life-cycle.
AB  - Experimental completion of the life-cycle of Paragonimus westermani (Trematoda:
      Troglotrematidae) (diploid type) from egg to adult has been achieved in the
      laboratory for the first time. A dog was fed metacercariae of P. westermani from
      naturally infected freshwater crabs. Geothelphusa dehaani. The adult flukes were
      recovered and their eggs were incubated in water at 28 degrees C, hatching after
      20 days. Laboratory reared marsh snails, Semisulcospira libertina, were exposed
      to miracidia from embryonated eggs. One of 47 snails became infected with a large
      number of 2nd generation rediae containing fully mature cercariae 245 days after
      exposure. Paragonimus-free crabs (G. dehaani) were then infected with the
      intramolluscan larvae. Of the 40 crabs examined 34-70 days after infection, 17
      were infected with a total of 84 metacercariae. A cat and 4 dogs were fed with 55
      metacercariae obtained. Eighty to 100 days later, a total of 40 flukes was
      recovered; 39 flukes were adults with eggs in their uteri.

PMID- 8132969
TI  - Prevalence of larval helminths in freshwater snails of the Kinmen Islands.
AB  - A survey of larval helminths in freshwater snails of Kinmen was conducted from
      1986 to 1987. Parasitological examinations of a total of 726 live snails
      collected from 25 loci revealed that 20 of 80 Bithynia fuchsiana were infected
      with metacercariae of Echinostoma gotoi and 36 with metacercariae of other
      echinostomes. Among 57 Radix auricularia swinhoei snails, 27 were infected with
      echinostomes and eight with metacercariae of other flukes. Of 20 Cipangopaludina
      chinensis, 18 were found with larvae of echinostomes. Larval trematodes were also
      found in three of 37 Austropeplea ollula and two of 87 Gyraulus spirillus. Third
      stage larvae of Parastrongylus cantonensis were found in Ampullarius
      canaliculatus (5/103), Sinotaia quadrata (20/141), Hippeutis umbilicalis cantori
      (1/70) and Gyraulus spirillus (2/87). Segmentina hemisphaerula were not infected.
      Cercariae of Centrocestus formosanus, Haplorchis pumilio and a xiphidiocercaria
      were found in three, two and two specimens, respectively, of 37 Thiara
      tuberculata.

PMID- 8132970
TI  - Effect of antibiotics on protein synthesis in filarial parasites.
AB  - Acanthocheilonema viteae, Litomosoides carinii and Setaria cervi were found to
      actively synthesize proteins in vitro. Different centrifugation fractions and
      their TCA-precipitable fractions were assessed for the distribution of newly
      synthesized proteins. Penicillin and streptomycin inhibited the process in A.
      viteae. The synthesis in S. cervi was susceptible to puromycin, chloramphenicol,
      cycloheximide, neomycin and polymyxin B. The process in L. carinii was strongly
      blocked by puromycin while chloramphenicol had no significant effect.

PMID- 8132971
TI  - Partial characterization of proteolytic enzymes in different developmental stages
      of Ostertagia ostertagi.
AB  - Proteolytic enzymes present in extracts of third (L3) and fourth (L4) stage
      larvae and adults of the cattle nematode Ostertagia ostertagi were defined on the
      basis of pH optima and proteinase inhibitor sensitivity in spectrophotometric
      assays using azocasein and elastin-orcein as protein substrates. Evidence that
      different classes of proteinases are expressed in a stage specific manner was
      provided by the contrasting pH optima and inhibitor sensitivities shown by the
      enzymes in the different parasite stages. Stage specificity was confirmed by
      gelatin-substrate analysis. In addition, proteolytic activity was sought in the
      excretory/secretory products (ES) of the L4 following simple in vitro culture.
      Contrasting pH and inhibitor sensitivities as well as gelatin-substrate analysis
      showed that different proteinases were present in somatic L4 extracts and L4 ES
      products. The secreted proteinases may be useful targets for serodiagnosis or
      vaccination.

PMID- 8132972
TI  - Use of body fluid of adult female Ascaris suum as an antigen in the enzyme-linked
      immunosorbent assay (ELISA) for diagnosis of swine ascariosis.
AB  - The Enzyme-linked immunosorbent assay (ELISA) was used to detect Ascaris suum
      antibodies in swine sera with adult body fluid (ABF) as an antigen. The assay was
      standardized with respect to the antigen concentration and serum and conjugate
      dilutions. Cross reaction was found between the antigen and the sera from the
      swine infected with Metastrongylus apri. The ELISA was more sensitive than the
      complement fixation test. Five protein peaks were obtained from ABF by gel
      filtration on Sephacryle S-300. Fraction 1 was the most specific. A 105 kDa
      protein in the fraction reacted with swine IgG in the serum of infected animals
      in Western blot analysis.

PMID- 8132973
TI  - Application of small doses of copper salts (basic and neutral) to Ascaridia galli
      infected chicks.
AB  - Male Hisex chicks were used in two experiments to investigate the interaction
      between Ascaridia galli infection and supplemental copper from basic and neutral
      salts. This was assessed by means of body weights, mortality, parasite burden and
      liver copper level. Cu2(OH)3Cl reduced the number of parasites but CuSO4.5H2O and
      CuCO3.Cu(OH)2.nH2O did not affect the parasite burden.

PMID- 8132974
TI  - A seroepidemiological study of human Toxocara infection in the Slovak Republic.
AB  - Sera of 908 blood donors, average age 35 years, living in towns and villages of
      the Slovak Republic were tested for Toxocara canis antibodies using an ELISA-IgG
      test. The seroprevalence in the healthy population was estimated at 13.65%.
      Antibodies were predominantly demonstrated in the sera from persons living in
      rural communities (17.09%) compared to the sera investigated from urban
      communities (11.82%). Women had a significantly higher seropositivity than men.
      The serological response in 2703 sera from patients suspected of toxocarosis was
      compared with their clinical manifestation, sex and age. Toxocara antibodies were
      found in 27.41% of suspected patients. Although the seroprevalence in adults was
      significantly higher among women than men, in children, boys had a higher
      seroprevalence than girls. The main clinical manifestations were leucocytosis and
      eosinophilia (46%), ocular disorders (36%), lung, liver and neurological
      disorders (26%). The most severe forms of this disease were observed in 2 to 5
      year-old children with geophagy.

PMID- 8132975
TI  - A simplified method for the fractionation of Gnathostoma-specific antigens for
      serodiagnosis of human gnathostomosis.
AB  - Specific immunoreactive components present in crude somatic extract and in
      excretory-secretory (ES) products of Gnathostoma spinigerum advanced third-stage
      larvae (L3) were identified by Western blotting and their diagnostic potential
      evaluated by indirect ELISA. Although both crude antigen preparations were highly
      complex, the ES antigen gave a more satisfactory diagnostic result. Most G.
      spinigerum specific components present in the somatic and ES preparations had
      molecular weights below 29 kD and were not glycosylated, judging from the
      concanavalin A staining pattern. Specific diagnostic antigens were prepared by
      subjecting the crude preparations to SDS-PAGE. Low molecular weight components
      were identified and electroeluted from the gel. Excess SDS was removed by the use
      of an ion retardation resin. The antigens obtained by this relatively simple
      procedure were found to be highly specific for G. spinigerum. Sensitivity,
      specificity, and positive and negative predictive values for the assay using the
      fractionated somatic antigen were 100%.

PMID- 8132976
TI  - Levels of ecdysteroid-like material in adults of Nippostrongylus brasiliensis
      during the intestinal phase.
AB  - Total ecdysteroid-like immunoreactive material was assayed and quantified in
      adults of the parasitic nematode N. brasiliensis during the intestinal phase in
      the rat in order to detect possible physiological fluctuations in titre. Worms of
      the same sex isolated from one rat were pooled in order to quantify ecdysteroids
      using enzyme immunoassay (EIA). The concentration of ecdysteroids fluctuated
      during adult life according to the sex and the age of the parasite. Important
      differences of levels of ecdysteroid-like compounds between the two sexes of
      parasites were noted particularly at 128 and 168 h post-infection. The peak at
      128 h, present in female, but not in male worms, corresponds to the time of egg
      laying. Following HPLC-EIA analysis, the presence of ecdysone, 20-hydroxyecdysone
      and apolar ecdysteroid-like material was ascertained during this peak. The
      physiological role and the possible origin of ecdysteroids in this nematode are
      discussed.

PMID- 8132977
TI  - Development of Proteocephalus torulosus in the intermediate host under
      experimental conditions.
AB  - The development of the tapeworm Proteocephalus torulosus (Batsch, 1786) (Cestoda:
      Proteocephalidae), a parasite of cyprinid fish, was studied in the intermediate
      host under experimental conditions. The eggs of P. torulosus were typified by a
      relatively small outer envelope (hyaline membrane) and a thick middle layer
      surrounding the oncosphere. Incubation of P. torulosus eggs at different
      temperatures revealed the ability of some oncospheres to survive and remain
      infective to the intermediate host for up to 5 weeks at 5-7 degrees C, 12 days at
      10-12 degrees C, and 8 days at 20-22 degrees C. Of 8 copepod species used in
      these experiments, complete development of larvae was observed only in Cyclops
      strenuus. Growth was completed in 9-12 days at 20-22 degrees C and four weeks at
      9-10 degrees C. During development the cercomer was not observed. The infectivity
      of larvae from C. strenuus for the definitive hosts, cyprinid fish, was very low
      and only one chub of 26 fish used for feeding experiments (21 chub, Leuciscus
      cephalus, 3 bleak, Alburnoides bipunctatus, 1 rudd, Scardinius erythrophthalmus-
      all the family Cyprinidae, and 1 loach, Noemacheilus barbatulus--the family
      Cobitidae) became infected.

PMID- 8132978
TI  - The role of dissolved carbon dioxide and whole bile in the in vitro activation of
      Taenia taeniaeformis oncospheres.
AB  - Dissolved carbon dioxide was deemed not to be an important factor in the
      activation of Taenia taeniaeformis oncospheres. Rabbit bile was found to provide
      the most appropriate whole bile for in vitro activation of oncospheres.

PMID- 8132979
TI  - Molecular epidemiology and Legionnaire's disease.

PMID- 8132980
TI  - Nosocomial infection control in Latin America.

PMID- 8132981
TI  - Evaluation of rooms with negative pressure ventilation used for respiratory
      isolation in seven midwestern hospitals.
AB  - OBJECTIVE: To determine the number and efficacy of respiratory isolation
      facilities in St. Louis hospitals and to assess the mechanisms in place for
      evaluating function of hospital ventilation systems. DESIGN: A prospective multi
      hospital surveillance study using direct observation and a standardized
      questionnaire. SETTING: Seven hospitals (including university-affiliated large
      teaching, private community, private teaching, and private nonteaching adult
      hospitals, and one pediatric teaching hospital) in St. Louis, Missouri.
      MEASUREMENTS: Actual direction of airflow in rooms designated for respiratory
      isolation was measured using smokesticks. Hospital demographic information,
      respiratory isolation policies, and frequency of ventilation tests were provided
      by infection control personnel. RESULTS: One hundred twenty-one (3.4%) of 3,574
      hospital rooms were designed to have negative pressure ventilation suitable for
      respiratory isolation. The percentage of isolation rooms in each institution
      ranged from 0.4% (92 of 486) to 93% (39 of 42). Only three (43%) of seven
      hospitals had intensive care respiratory isolation rooms, and none had isolation
      rooms in the emergency department. No hospital had tested routinely the efficacy
      of the negative pressure ventilation, and two (28%) of seven had tested airflow
      for the first time in the past year. We tested 115 (95%) of 121 isolation rooms.
      With the doors closed, 52 (45%) of 115 designated negative pressure rooms
      actually had positive airflow to the corridor. The number of negative pressure
      rooms and the presence or absence of anterooms did not predict correct direction
      of airflow. There was a significant difference among hospitals in the percentage
      of designated isolation rooms that had truly negative pressure (P < 0.0001).
      Hospital age, size, and type correlated with correct direction of airflow (P <
      0.0001). CONCLUSION: In the hospitals studied, only a small number of rooms were
      designated for respiratory isolation, and the performance of these was not tested
      routinely. High-risk areas including intensive care units and emergency rooms
      were not equipped to provide respiratory isolation. The direction of airflow in
      respiratory isolation rooms was not always correct and should be evaluated
      frequently.

PMID- 8132982
TI  - A case-control study of nosocomial ampicillin-resistant enterococcal infection
      and colonization at a university hospital.
AB  - OBJECTIVE: To assess risk factors for colonization and nosocomial infection with
      ampicillin-resistant enterococci (ARE). DESIGN: Patients with ampicillin
      resistant enterococci were compared retrospectively by logistic regression
      analysis with controls harboring susceptible strains. ARE were characterized by
      whole plasmid DNA analysis and restriction enzyme analysis of plasmid (REAP) DNA
      with EcoRI. SETTING: The study was done at a 1,125 bed, tertiary-care teaching
      hospital in North Carolina with patients from whom enterococci were isolated from
      June 1, 1989, to March 30, 1991. PATIENTS: The final study group comprised 44
      cases with nosocomially-acquired colonization or infection with ARE and 100
      controls with ampicillin-susceptible strains. Clinical and epidemiological risk
      factors for ARE were abstracted by chart review. RESULTS: After controlling for
      age and site of infection, patients with ARE were more likely to have been
      admitted previously to our hospital and to have received third-generation
      cephalosporins and clindamycin. However, only advanced age and clindamycin
      therapy were independently associated with presence of ARE. REAP with EcoRI
      showed 20 groups of enterococci on 19 different wards. CONCLUSIONS: These results
      suggest that ARE are endemic and multifocal in origin in our hospital and that
      advanced age and use of clindamycin are important selective risk factors for ARE
      colonization and infection.

PMID- 8132983
TI  - A nosocomial pseudo-outbreak of Mycobacterium xenopi due to a contaminated
      potable water supply: lessons in prevention.
AB  - OBJECTIVES: To determine risk factors for Mycobacterium xenopi isolation in
      patients following a pseudo-outbreak of infection with the organism. DESIGN:
      Retrospective cohort analysis of mycobacteriology laboratory specimen records and
      frequency-matched case-control study of hospital patients. SETTING: General
      community hospital. PATIENTS: For the case-control study, 13 case patients and 39
      randomly selected controls with mycobacterial cultures negative for M xenopi,
      frequency matched by specimen source, whose specimens were submitted from June
      1990 through June 1991. RESULTS: Between June 1990 and June 1991, M xenopi was
      isolated from 13 clinical specimens processed at a midwestern hospital, including
      sputum (n = 6), bronchial washings (2), urine (4), and stool (1). None of the
      patients with M xenopi-positive specimens had apparent mycobacterial disease,
      although five received antituberculosis drug therapy for a range of one to six
      months. Specimens collected in a nonsterile manner were more likely to grow the
      organism than those collected aseptically (3.1% versus 0, relative risk =
      infinity, P = 0.003). M xenopi isolation was attributed to exposure of clinical
      specimens to tap water, including rinsing of bronchoscopes with tap water after
      disinfection, irrigation with tap water during colonoscopy, gargling with tap
      water before sputum collection, and collecting urine in recently rinsed bedpans.
      M xenopi was isolated from tap water in 20 of 24 patient rooms tested, the
      endoscopy suite, and the central hot water mixing tank, but not from water in the
      microbiology laboratory. The pseudo-outbreak occurred following a decrease in the
      hot water temperature from 130 degrees F to 120 degrees F in 1989. CONCLUSIONS:
      Maintenance of a higher water temperature and improved specimen collection
      protocols and instrument disinfection procedures probably would have prevented
      this pseudo-outbreak.

PMID- 8132984
TI  - State regulation of hospital water temperature.
AB  - OBJECTIVE: The purpose of this study was to determine current regulations and
      policies in the United States concerning maximal water temperatures in acute care
      hospitals. DESIGN: A standardized questionnaire administered by telephone to
      health department officials from 50 states and the District of Columbia. SETTING:
      State Health Departments in the 50 states and the District of Columbia. RESULTS:
      All states responded to the survey. Respondents from 39 states (77%) reported
      regulating maximum allowable hospital water temperature at a mean of 116 degrees
      F (median, 120 degrees F; mode 110 degrees F; range, 110 degrees F to 129 degrees
      F). Twelve states (23%) have no regulations for maximum water temperature. Of the
      39 states regulating maximum water temperature, 30 (77%) routinely monitor
      hospital compliance. Nine states (23%) conduct inspections only in response to a
      complaint or incident. CONCLUSIONS: There is great variation among the states
      with respect to the existence, enforcement, and specific regulations controlling
      hospital water temperature. Risk-benefit and cost-effectiveness analyses would
      help to assess the risk of scald injuries at water temperatures that will inhibit
      microbial contamination.

PMID- 8132985
TI  - Global aspects of infection control.

PMID- 8132986
TI  - The use of statistical process control charts in hospital epidemiology.

PMID- 8132987
TI  - Needleless and needle protection devices: a second look at efficacy and
      selection.

PMID- 8132988
TI  - HIV-infected scientist claims AIDS vaccine does not work.

PMID- 8132989
TI  - Court rules that patient may sue HIV-infected doctor for emotional distress.

PMID- 8132990
TI  - WHO estimates 13 million HIV-positive women by the year 2000.

PMID- 8132991
TI  - Fans, filters, or rays? Pros and cons of the current environmental tuberculosis
      control technologies.

PMID- 8132992
TI  - Occupational infectious diseases or infectious occupational diseases? Bridging
      the views on tuberculosis control.

PMID- 8132993
TI  - OSHA enforcement policy for occupational exposure to tuberculosis.

PMID- 8132994
TI  - OSHA enforcement policy and procedures for occupational exposure to tuberculosis.

PMID- 8132995
TI  - A ventilation-filtration unit for respiratory isolation.
AB  - OBJECTIVE: The development of a new method for achieving respiratory isolation in
      hospitals, clinics, and residential facilities, in response to the increasing
      risk of transmission of tuberculosis and the limitations of the currently
      available isolation systems. DESIGN: Ultraviolet (UV) light and ultra-low
      penetration air filtration were combined with a ventilation unit and adapted for
      use in modular isolation rooms or for conversion of existing rooms. RESULTS: The
      ventilation-filtration unit efficiently cleared bacterial aerosols and particles
      > 0.2 microns from the air, maintained required negative pressures and airflows,
      and provided directional airflow within rooms.

PMID- 8132996
TI  - Nonincreased risk of nosocomial infection during a 22-day housekeeping personnel
      strike in a tertiary hospital.
AB  - BACKGROUND: From April 2-23, 1992, the housekeeping staff of the University of
      Granada Hospital was on strike. Measures were implemented to minimize the effects
      of the strike on patients' health and especially to diminish the risk of hospital
      infection. OBJECTIVE: To assess the risk of nosocomial infection during the
      housekeeping personnel strike. SETTING: An 800-bed, tertiary care hospital.
      METHODS: A case-cohort approach was used. One hundred forty-eight infected
      patients (with 184 hospital infections) were detected prospectively from March 1,
      1992, to May 31, 1992. A sample of 459 of the base population (patients admitted
      during the same period) was selected. Information on relevant risk factors for
      hospital infection was abstracted from patients' clinical charts after hospital
      discharge. Crude odds ratios and adjusted (by proportional hazards model)
      relative risks (RRs) for the strike period were estimated. RESULTS: Risk of
      nosocomial infection did not increase during the strike period (multiple-risk
      factor adjusted RR = 0.99, 0.96 to 1.01/day of strike). Similar results were
      observed for major sites of infection (especially surgical wound) and major areas
      of the hospital (including gynecology, surgery, and intensive care). CONCLUSION:
      We concluded that there was no increase in the risk of nosocomial infection
      during the housekeeping strike.

PMID- 8132997
TI  - Sporicidal activity of chemical sterilants used in hospitals.
AB  - OBJECTIVE: The current study was designed to assess the sporicidal activity of
      chemical sterilants using the Association of Official Analytical Chemists (AOAC)
      sporicidal test. Chemical sterilants are used most commonly in the healthcare
      setting to disinfect medical instruments such as endoscopes. This study was
      undertaken to evaluate the efficacy of several newer formulations of
      glutaraldehydes and hydrogen peroxide as chemical sterilants. DESIGN: Using the
      AOAC test the following agents were tested: two 2% alkaline glutaraldehydes (2%
      Alk-Glut), 2% acid glutaraldehyde (2% Acid Glut), 2% glutaraldehyde-7.05% phenol
      1.20% sodium phenate, 10% glutaraldehyde-0.5% phenylphenol-0.1% tertiary
      amylphenol, and 6% hydrogen peroxide (H2O2). Growth in > 1 of 60 seeded
      penicylinders is considered by the AOAC to indicate failure of sporicidal
      activity. RESULTS: Test results of the six disinfectants against Bacillus
      subtilis using the manufacturers' specified use-dilution and exposure time were:
      0/60 with 2% Alk-Glut (product 1) at 10 hours, 0/60 with 2% Alk-Glut (product 2)
      at 8 hours, 0/60 with 2% Acid Glut at 10 hours, 2/60 with 2% glutaraldehyde-7.05%
      phenol-1.20% sodium phenate at 6.75 hours, 0/60 with a 1:5 dilution (2.0% Glut)
      of 10% glutaraldehyde-0.5% phenylphenol-0.1% amylphenol at 6 hours, 59/60 with a
      1:20 dilution (0.5% Glut) of 10% glutaraldehyde-0.5% phenylphenol-0.1% tertiary
      amylphenol at 12 hours and 0/60 with 6% H2O2 at 6 hours. Test results against
      Clostridium sporogenes were: 2/60 with 2% Alk-Glut (product 1) at 10 hours, 1/60
      with 2% Alk-Glut (product 2) at 8 hours, 1/60 with 2% Acid Glut at 10 hours, 2/60
      with undiluted 2% glutaraldehyde-7.05% phenol-1.20% sodium phenate at 6.75 hours,
      6/60 with a 1:5 dilution (2% Glut) of 10% glutaraldehyde-0.5% phenylphenol-0.1%
      amylpenol at 6 hours, 60/60 with a 1:20 dilution (0.5% Glut) of 10%
      glutaraldehyde-0.5% phenylphenol-0.1% amylpenol at 12 hours, and 0/60 with 6%
      H2O2 at 6 hours. Dilutions of 2% glutaraldehyde-7.05% phenol-1.20% sodium phenate
      yielded the following results against C sporogenes: 59/60 with a 1:8 dilution
      (0.25% Glut) at 6.75 hours, 60/60 with a 1:16 dilution (0.125% Glut) at 6.75
      hours, 11/90 with a 1:8 (0.25% Glut) dilution at 12 hours, and 60/60 with a 1:16
      dilution (0.125% Glut) at 12 hours. CONCLUSIONS: Both 2% acid and alkaline
      glutaraldehydes are effective chemical sterilants. Diluting glutaraldehyde-based
      sterilants below 2% glutaraldehyde resulted in failure to kill spores of B
      subtilis and C sporogenes.

PMID- 8132998
TI  - Cryptococcal ventricular-peritoneal shunt infection: clinical and epidemiological
      evaluation of two closely associated cases.
AB  - OBJECTIVE: To determine the cause of meningitis associated with Cryptococcus
      neoformans in two patients with recent ventricular-peritoneal (VP) shunt
      placement. DESIGN: A retrospective review of materials, records, and concurrent
      cases of VP shunt procedures. Isolates of C neoformans from each patient were
      submitted for analysis by colony morphology, biochemical testing, and karyotyping
      by pulsed-field electrophoresis. SETTING: Two 400-bed community hospitals.
      PATIENTS: Two immunocompetent patients presented with symptoms of progressive
      hydrocephalus in August 1991. Each received a VP shunt on the same day by the
      same surgeon using materials from a common vendor and hospital. RESULTS: Both
      patients presented within six to eight weeks with symptoms of fever, headache,
      rash, and cultures of cerebrospinal fluid (CSF) that yielded C neoformans. Each
      patient recovered after therapy with amphotericin B and flucytosine followed by
      several months of fluconazole, although one required replacement of the VP shunt
      for cure. Review of each patient's history and CSF characteristics at the time of
      shunt placement suggested reactivation of a preexisting infection. Isolates of C
      neoformans from each patient were submitted for analysis by colony morphology,
      biochemical testing, and karyotyping by pulsed-field electrophoresis. Each
      isolate was found to be unique by chromosomal karyotyping. CONCLUSIONS: Our data
      and previous reports suggest that cryptococcal VP shunt infections appear to be a
      complication of shunts placed in previously infected persons rather than
      nosocomial transmission of cryptococcus during placement.

PMID- 8132999
TI  - The use of germicidal lamps to control tuberculosis in healthcare facilities.

PMID- 8133000
TI  - Selecting optimal statistical tools.

PMID- 8133001
TI  - Court supports hospital's decision to transfer HIV-infected surgical technician.

PMID- 8133002
TI  - Hospital offers free HIV testing to patients exposed to lab tech.

PMID- 8133003
TI  - Measles immunity in a population of healthcare workers.
AB  - OBJECTIVES: To evaluate measles seroprevalence among cohorts of new employees and
      to evaluate vaccine responses of susceptible adult healthcare workers. DESIGN:
      New employees were screened for measles susceptibility as part of employee
      evaluations. Anti-IgG measles antibody tests were completed on 2,473 workers.
      Demographic, measles history, and measles vaccination information was collected
      using a short questionnaire. Susceptible workers were vaccinated and screened for
      vaccine responses following vaccination. RESULTS: Ninety-three workers (4%) were
      seronegative, and 56 (2%) were equivocal. Individuals in the youngest cohort
      (born after 1956) were significantly more likely to be susceptible than those in
      the middle cohort (born 1951 to 1956) and those in the oldest cohort (born before
      1951) (P < 0.01). The middle cohort included eight (5%) of the 149 seronegative
      or equivocal workers. Among the members of the youngest cohort, those from the
      United States were more likely to be susceptible (P < 0.01) than those from
      outside the United States. Of the 106 vaccinated susceptible workers whose follow
      up serologies were determined, 90 (85%) developed positive IgG serologies, six
      had equivocal results, and 10 were seronegative. Eleven of the 16 non- or
      hyporesponders were revaccinated and re-evaluated; nine developed low positive
      IgG antimeasles levels, one exhibited an equivocal response, and one failed to
      respond. CONCLUSIONS: A small but important proportion of healthcare workers are
      susceptible to measles. Whenever feasible, measles immunity programs for
      healthcare workers should include workers born before 1957. Of workers born after
      1956, those from outside the United States are more likely to be immune than
      workers from inside the United States. Using the currently available vaccine,
      revaccination of initial non- or hyporesponders appears to be effective.

PMID- 8133005
TI  - Nosocomial transmission of Salmonella gastroenteritis to laundry workers in a
      nursing home.
AB  - BACKGROUND: Outbreaks of salmonella gastroenteritis in nursing homes are common.
      Person-to-person transmission to nursing home personnel occurs occasionally, but
      infection of laundry staff as a result of handling soiled linen rarely has been
      reported. OBJECTIVE: To examine the nosocomial transmission of infection to
      laundry staff during an outbreak of salmonellosis in a nursing home. SETTING: A
      250-bed nursing home in a rural Tennessee county. METHODS: Residents and staff of
      the nursing home were interviewed and cultures of stool samples examined for
      enteric pathogens. RESULTS: Stool cultures from 32 residents and 8 employees were
      positive for Salmonella hadar. Infection among the residents was food-borne, but
      infection among employees likely represented secondary transmission, as none of
      the employees ate food prepared in the kitchen and their onset of symptoms
      occurred seven to 10 days after that of ill residents. Three laundry personnel
      who had no contact with residents were infected. Most of the ill residents (81%)
      were incontinent, which led to an increase in both the degree of fecal soiling
      and the amount of soiled linen received by the laundry during the outbreak.
      Laundry personnel regularly ate in the laundry room, did not wear protective
      clothing, and did not wear gloves consistently while handling soiled laundry.
      CONCLUSIONS: This investigation implicates linen soiled with feces as the source
      of nosocomial S hadar infection in laundry workers and underscores the importance
      of using appropriate precautions when handling linen.

PMID- 8133004
TI  - Measles-mumps-rubella immunization of susceptible hospital employees during a
      community measles outbreak: cost-effectiveness and protective efficacy.
AB  - OBJECTIVE: To determine cost-effectiveness and protective efficacy of a program
      to identify and immunize susceptible hospital employees during a measles
      outbreak. DESIGN: A cost analysis was made of blind measles-mumps-rubella (MMR)
      immunization versus directed MMR immunization based on 2,000 employees born after
      December 31, 1956. A directed MMR immunization program for susceptible employees
      was instituted. Actual costs of the program were calculated at the conclusion of
      the program. SETTING: A medical center complex with more than 4,000 employees,
      two acute care community hospitals, and a tertiary care children's hospital.
      RESULTS: A directed MMR immunization program was projected to be less expensive
      than blind immunization ($23,106 versus $70,720). MMR vaccine was administered to
      169 of 188 susceptible employees. Actual cost of the directed MMR immunization
      program was $25,384. CONCLUSIONS: The directed MMR immunization program was cost
      effective and prevented secondary cases among hospital employees during a
      community measles outbreak.

PMID- 8133006
TI  - The epidemiology of needlestick and sharp instrument accidents in a Nigerian
      hospital.
AB  - OBJECTIVES: To characterize the epidemiology of percutaneous injuries of
      healthcare workers (HCWs) in Ile-Ife, Nigeria. DESIGN: A cross-sectional survey
      of a random sample of HCWs regarding details of needlestick and sharp instrument
      injuries within the previous year. SETTING: University hospital and clinics in
      Ile-Ife, Nigeria. PARTICIPANTS: Hospital personnel with potential occupational
      exposure to patients' blood. RESULTS: Needlestick accidents during the previous
      year were reported by 27% of 474 HCWs, including 100% of dentists, 81% of
      surgeons, 32% of nonsurgical physicians, and 31% of nursing staff. The rate of
      needlestick injuries was 0.6 per person-year overall: 2.3 for dentists, 2.3 for
      surgeons, 0.4 for nonsurgical physicians, and 0.6 for nursing staff.
      Circumstances associated with needlestick injuries included unexpected patient
      movement in 29%, handling or disposal of used needles in 23%, needle recapping in
      18%, accidental stick by a colleague in 18%, and needle disassembly in 10%. Sharp
      instrument injuries were reported by 15% of HCWs and most commonly involved
      broken glass patient specimen containers (39%). Almost all HCWs were aware of the
      potential risk of HIV transmission through percutaneous injuries, and 91%
      considered themselves very concerned about their occupational risk of HIV
      acquisition. CONCLUSIONS: The high frequency of percutaneous exposure to blood
      among HCWs in this Nigerian hospital potentially could be reduced by simple
      interventions at modest cost.

PMID- 8133007
TI  - Attitudes of internal medicine residents regarding influenza vaccination.
AB  - OBJECTIVE: To survey the attitudes of internal medicine residents regarding the
      influenza vaccine and their reasons for accepting or refusing the vaccine during
      a hospitalwide immunization campaign. DESIGN AND PARTICIPANTS: Internal medicine
      residents responded to a written survey. SETTING: A university-owned, 891-bed,
      tertiary referral hospital and a 278-bed Veterans Administration hospital in
      Iowa. RESULTS: Immediately following the immunization campaign, 51% of residents
      had received the vaccine. Of those residents who were not vaccinated, 42% never
      had time to go to the vaccine clinic, but only 8% worried about side effects of
      the vaccine. Residents whose clinics were staffed by infectious disease
      subspecialists were significantly more likely to be vaccinated (odds ratio =
      2.55; CI95 = 1.01 to 6.42) than residents working with general internists or
      other subspecialists. CONCLUSIONS: Knowledge, vaccine availability, and social
      pressure all increase the likelihood that residents will be vaccinated. Faculty,
      particularly those interested in infectious diseases, may influence residents to
      accept the vaccine.

PMID- 8133008
TI  - Human immunodeficiency virus infection in pregnancy: epidemiology and prevention
      of vertical transmission.
AB  - The preponderance of AIDS cases in women during their reproductive years demands
      attention to primary prevention, early recognition, and appropriate
      interventions. Increases in the epidemic among injection drug users and
      heterosexually exposed persons have resulted in an increased impact of HIV/AIDS
      among women and children. It is clear that vertical transmission of HIV can occur
      early in pregnancy, during labor and delivery, or in the postpartum period. For
      these reasons, prevention strategies must be comprehensive and include primary
      prevention and appropriate intervention during pregnancy and in the peripartum
      and postpartum area. Stringent infection control techniques are imperative during
      delivery and in the postpartum period, even in the absence of clear data
      supporting this intervention. Recent data suggest that the cost of treating one
      adult patient with AIDS is approximately $100,000, making prevention and
      intervention imperative.

PMID- 8133009
TI  - Measles immunization in HCWs.

PMID- 8133010
TI  - Measles and healthcare workers.

PMID- 8133011
TI  - Valaciclovir more effective than acyclovir in reducing pain from shingles.

PMID- 8133012
TI  - Measles immunity in employees of a multihospital healthcare provider.
AB  - OBJECTIVE: To assess the potential for nosocomial measles transmission by
      measuring seropositivity among healthcare workers in Utah. DESIGN: Blood
      specimens were collected for measurement of measles IgG antibody by enzyme
      immunoassay (EIA). Individuals with undetectable or equivocal antibody levels
      were considered at risk for infection. Employees were grouped according to the
      decade of their birth, and analyses of serological findings were done by the
      Mantel-Haenszel chi-square test for trend. SETTING: The study was performed in a
      healthcare organization comprised of six urban and 10 rural hospitals.
      PARTICIPANTS: Employees (n = 5825) were tested regardless of age, history of
      disease, or immunization. RESULTS: There were 599 employees (10.3%) who were
      nonimmune. A trend showing age-related differences in immunity was not noted
      among employees born prior to 1957 (4.7% nonimmune). However, for employees born
      after that time, there was a significant age-associated increase in the
      percentage of susceptible individuals (P = 0.00001). The rate of susceptibility
      was 8.1% for individuals born between 1957 and 1959, 16.3% for individuals born
      during the 1960s, and 33.7% for those born in the 1970s. CONCLUSIONS: We
      concluded that employees born after 1960 represent a material risk for
      transmission of measles in the hospital setting. Despite the low percentage of
      susceptibility among those born before 1957, the 144 susceptible individuals in
      this group also are at risk for measles transmission. Thus, during periods of
      increased measles prevalence, we would recommend screening all healthcare workers
      regardless of age and vaccinating those who are susceptible.

PMID- 8133013
TI  - Bibliography of the current world literature in hypertension.

PMID- 8133014
TI  - Prostaglandins and their receptors: I. Pharmacologic receptor description,
      metabolism and drug use.

PMID- 8133015
TI  - Characterization of the muscarinic receptors in the mesenteric vascular bed of
      spontaneously hypertensive rats.
AB  - OBJECTIVE: The nature of the muscarinic (M) receptor subtype mediating
      endothelium-dependent vasodilation was investigated in Wistar-Kyoto (WKY) rats
      and spontaneously hypertensive rats (SHR). DESIGN: Characterization of the
      muscarinic receptor mediating vasodilation and the possible hypertension-induced
      effects on the nature of this receptor, which have both received little attention
      in resistance vessels of the SHR. METHODS: After a methoxamine-induced
      vasoconstriction, the vessels were dilated with acetyl-beta-metacholine (MCh).
      The MCh-induced vasodilation was analysed by means of the M1-selective antagonist
      pirenzepine, the M2-selective antagonists AF-DX116 and AQ-RA 741 and the M3
      selective antagonists 4-DAMP and p-FHHSiD. The potency of these compounds was
      quantified by means of pA2 values. Atropine, a non-selective muscarinic
      antagonist, was used for comparison. RESULTS: The rank order of potency for the
      muscarinic receptor antagonists in preparations taken from SHR and WKY rats
      appears to be atropine > 4-DAMP > p-FHHSiD > pirenzepine > AQ-RA 741 > AF-DX 116.
      This rank order corresponds to that found in isolated conduit arteries.
      CONCLUSIONS: The pA2 values for the various compounds were not significantly
      different in SHR and WKY rat preparations, indicating that the nature of this
      receptor is not influenced by hypertension. The high potency of the M3-selective
      drugs and the weak activity of pirenzepine and the M2-selective antagonists
      suggest a major role of M3-receptors in the cholinergic vasodilation in the
      perfused mesenteric vascular bed both in SHR and WKY rat preparations.

PMID- 8133016
TI  - Effects of the arterial vasodilator minoxidil on cardiovascular structure and
      sympathetic activity in spontaneously hypertensive rats.
AB  - OBJECTIVE AND DESIGN: In spontaneously hypertensive rats (SHR) arterial
      vasodilators do not cause regression and might cause further progression of
      cardiac hypertrophy. To assess whether these effects extend to the vasculature,
      and to examine the possible mechanisms involved, cardiac and mesenteric arterial
      structure was evaluated with respect to changes in cardiac volume load and
      cardiac and arterial sympathetic activity during long-term (5- and 10-week)
      treatment of 16-week-old SHR with the arterial vasodilator minoxidil, alone or in
      combination with the diuretic hydrochlorothiazide. RESULTS: Despite causing a
      persistent decrease in blood pressure in SHR, minoxidil further increased left
      and right ventricular weights and left ventricular internal diameter. In
      combination with hydrochlorothiazide, minoxidil caused concentric, rather than
      eccentric, left ventricular hypertrophy. In the mesenteric arterial bed of SHR,
      minoxidil increased the lumen of the superior mesenteric artery, and prevented
      further increases in the medial area of the large and small mesenteric arteries.
      The increase in lumen size of the superior mesenteric artery by minoxidil was
      abolished when hydrochlorothiazide was added to the treatment. After 10 weeks'
      treatment with minoxidil, noradrenaline turnover rates were still significantly
      increased in the left ventricle but were decreased in the mesenteric arteries in
      the SHR. Minoxidil increased plasma and blood volumes, the increases being
      largely prevented by concomitant diuretic treatment. CONCLUSIONS: We conclude
      that there are regional differences in the response of the cardiovascular system
      to minoxidil in SHR. Some of these differences may be related to differences in
      regional sympathetic activity, whereas volume load appears to play a modulatory
      role.

PMID- 8133017
TI  - The role of activated vascular angiotensin II generation in vascular hypertrophy
      in one-kidney, one clip hypertensive rats.
AB  - OBJECTIVE: To investigate the role of vascular angiotensin II (Ang II) in the
      vascular thickening of one-kidney, one clip (1-K, 1C) hypertensive rats, which
      show normal plasma renin activity. METHODS: The type 1 Ang II receptor antagonist
      TCV-116 (1 mg/kg per day), the angiotensin converting enzyme (ACE) inhibitor
      delapril (20 mg/kg per day), hydralazine (20 mg/kg per day) or vehicle were
      administered to four groups of 1-K, 1C rats aged 6-10 weeks. Vehicle was also
      given to uninephrectomized rats. RESULTS: The aortae of 1-K, 1C rats contained
      significantly higher levels of Ang II than those of uninephrectomized rats and
      showed hypertrophy, but not hyperplasia of their medial smooth muscle cells.
      Hypertrophy was estimated by immunohistochemical staining of alpha-actin.
      Hyperplasia was estimated by DNA content and incorporation of 5-bromo-2'
      deoxyuridine. The blood pressure of the 1-K, 1C rats was not affected by either
      TCV-116 or delapril, even at doses sufficient to induce depressor effects in
      spontaneously hypertensive rats. However, subdepressor doses of TCV-116 and
      delapril both significantly reduced the alpha-actin-stained area to 78 and 73%,
      respectively, of that in the 1-K, 1C rats, whereas a depressor dose of
      hydralazine did not affect the alpha-actin-stained area. The level of Ang II in
      the aorta, but not in plasma, was suppressed by delapril but not by hydralazine.
      CONCLUSIONS: These results suggest strongly that vascular Ang II plays a major
      role in the development of vascular hypertrophy, independently of plasma Ang II,
      bradykinin and ACE-independent pathways of Ang II generation, and in the
      regulation of blood pressure in this normoreninaemic hypertensive model.

PMID- 8133018
TI  - Brain capillary density and cerebral blood flow after occlusion of the middle
      cerebral artery in normotensive Wistar-Kyoto rats and spontaneously hypertensive
      rats.
AB  - OBJECTIVE: In order to elucidate why spontaneously hypertensive rats (SHR)
      develop larger brain infarcts distal to an arterial occlusion than normotensive
      Wistar-Kyoto (WKY) rats, we determined the surface and volume densities of
      cerebral capillaries, and the regional cerebral blood flow distal to an arterial
      occlusion in SHR and WKY rats. DESIGN: Occlusion of the middle cerebral artery
      was chosen because the middle cerebral artery territory is most commonly affected
      by cerebral infarcts in man. METHODS: Surface and volume densities of capillaries
      in the neocortex of the middle cerebral artery territory were measured by
      stereological techniques on histological sections. Fifteen minutes after ligation
      of the right middle cerebral artery, regional cerebral blood flow was measured
      autoradiographically by the [14C]-iodoantipyrine method. RESULTS: The capillary
      density of the neocortex did not differ between the SHR and WKY rats. The blood
      flow was significantly lower within the middle cerebral artery territory in the
      SHR than in the WKY rats. CONCLUSIONS: The reduced blood flow distal to the
      occlusion in SHR is probably a consequence of structural adaptation of arterial
      resistance vessels, rather than being caused by reduced capillary density.

PMID- 8133019
TI  - Inhibition by nitroprusside of platelet calcium mobilization: evidence for
      reduced sensitivity to nitric oxide in essential hypertension.
AB  - OBJECTIVE: Although platelets from patients with moderate hypertension are
      abnormally sensitive to agonist-induced aggregation, their sensitivity to
      antagonists is not known. Nitric oxide (NO) is an endogenous antagonist of
      platelet function. The objective of this study was to determine whether platelet
      sensitivity to the inhibitory activity of sodium nitroprusside, a donor of NO, is
      abnormal in hypertension. DESIGN AND METHODS: Untreated patients with
      uncomplicated essential hypertension (mean arterial pressure > 120 mmHg) were
      studied. The rise in cytosolic calcium in response to 9,11-deoxy-11 alpha, 9
      alpha-epoxymethanoprostaglandin F2 alpha (U46619, a thromboxane mimetic) was
      measured in fura-2-loaded platelets from 20 patients and 15 normotensive healthy
      subjects. Inhibition by sodium nitroprusside was measured in a further group of
      14 patients and 20 normotensive subjects. RESULTS: Basal cytosolic calcium
      concentration and the rise in this parameter induced by U46619 were significantly
      greater in platelets from hypertensive patients than in those from normotensive
      controls. The mean half-maximal inhibitory concentration of nitroprusside to
      calcium mobilization induced by 3 mumol/l U46619 was 3.1-fold greater in
      platelets from hypertensive patients than in those from controls (95% confidence
      interval 1.6-6.0). CONCLUSION: The sensitivity of platelets to nitroprusside is
      reduced in essential hypertension. This reduced sensitivity to NO might influence
      the risk of arterial thrombosis in hypertensives.

PMID- 8133020
TI  - Enhanced blood pressure response to dietary salt in elderly women, especially
      those with small waist: hip ratio.
AB  - OBJECTIVE: To determine the blood pressure responses in elderly normotensive men
      and women to dietary sodium and to the diunsaturated fatty acid
      dihomogammalinolenic acid (DGLA), which is derived from linoleic acid. DESIGN:
      Blood pressure responses were assessed in 66 subjects (36 male, 30 female; mean
      age 65 years) on two diets differing by approximately 70 mmol/day sodium,
      combined with daily supplements of either 1 g DGLA or 1 g safflower oil, giving a
      four-group parallel design. After a common period of salt restriction and salt
      supplementation, two sets of parallel groups continued with either salt or
      placebo tablets. The study was blinded, except for dietary adjustments based on
      24-h urinary sodium excretion values measured once every 2 weeks. Blood pressures
      were also measured automatically once every 2 weeks. RESULTS: Urinary sodium
      excretion (sodium intake) correlated significantly with systolic and diastolic
      blood pressures. A strong interaction with sex (P < 0.001 for systolic blood
      pressure) reflected greater responsiveness in women to changing sodium intake. A
      second major determinant of blood pressure responsiveness was the waist: hip
      ratio, an index of central obesity; this correlation was independent of the
      initial sodium intake, initial blood pressure or body mass index. The waist: hip
      ratio was a powerful predictor of blood pressure changes with sodium intake in
      women only; women with android fat distribution were, similarly to men, less
      sensitive to dietary sodium. Daily supplements of 1 g DGLA doubled the
      concentration of DGLA in plasma but did not influence blood pressure.
      CONCLUSIONS: Among elderly normotensive subjects, women responded to changes in
      sodium intake with greater changes in blood pressure than men did. Furthermore,
      this response was strongly related to the gynaecoid distribution of body fat.

PMID- 8133021
TI  - Digitalis restores the forearm sympathetic response to cardiopulmonary receptor
      unloading in hypertensive patients with left ventricular hypertrophy.
AB  - OBJECTIVE: To investigate whether the impaired reflex response to cardiopulmonary
      baroreceptor unloading in hypertensive patients with left ventricular hypertrophy
      can be promptly improved by a pharmacological challenge. For this purpose we
      studied the effects of acute digitalis administration on cardiopulmonary
      baroreflex, evaluated by forearm noradrenaline spillover. METHODS: Eleven
      hypertensives with left ventricular hypertrophy and 10 age- and sex-matched
      normotensives underwent the application of -5 and -10 mmHg lower-body negative
      pressure (LBNP) before and after the administration of digitalis. Forearm
      noradrenaline spillover, measured using a tracer technique, was used to estimate
      the reflex sympathetic response. RESULTS: Under control conditions LBNP evoked a
      similar fall in right atrial pressure in the two study groups. In the
      normotensives there was a significant increase in forearm noradrenaline
      spillover. In the hypertensives no significant changes in forearm noradrenaline
      spillover were found. Intravenous administration of 0.02 mg/kg lanatoside C was
      associated with an increase in systolic blood pressure and a reduction in forearm
      noradrenaline spillover in both groups. In the normotensives the percentage
      change in forearm noradrenaline spillover induced by LBNP increased significantly
      in response to digitalis administration. However, digitalis restored the response
      of forearm noradrenaline spillover to LBNP in the hypertensives, so that no
      significant difference in this response was detected between the two study
      groups. Digitalis did not modify the effects of LBNP on cardiac pressures in
      either group. CONCLUSIONS: The present results demonstrate that administration of
      lanatoside C restores the response of forearm noradrenaline spillover to
      cardiopulmonary baroreceptor unloading in hypertensive patients with left
      ventricular hypertrophy. This indicates that the impairment of cardiopulmonary
      baroreflexes in these patients can be reversed by acute pharmacological
      treatment. Therefore, impairment of this reflex response seems to be related to
      functional rather than to structural abnormalities of the hypertrophied
      ventricle.

PMID- 8133022
TI  - The use of self-measured blood pressure determinations in assessing dynamics of
      drug compliance in a study with amlodipine once a day, morning versus evening.
AB  - OBJECTIVE: To test whether the time of administration influences the therapeutic
      response to a calcium antagonist taken once a day. Also, the dynamics of drug
      compliance and its impact on blood pressure control were investigated. DESIGN:
      Twenty outpatients with mild-to-moderate hypertension were included in a
      randomized, placebo-controlled open study. In a crossover design, all of the
      patients received 5 mg amlodipine, either in the morning or in the evening,
      during two consecutive 4-week treatment periods. METHODS: Blood pressure was
      taken by casual measurement, ambulatory 24-h monitoring (SpaceLabs 90202) and
      self-measurement at home, performed with a semi-automatic oscillometric device
      during the whole study period. Compliance was assessed using the Medication-Event
      Monitoring System (MEMS). RESULTS: Neither casual nor ambulatory day- or night
      time readings detected a significant difference between morning and evening
      administration. However, self-measurement documented significantly greater blood
      pressure reductions for morning than for evening administration. The MEMS showed
      different compliance on the days of ambulatory monitoring (100% with both drug
      regimens) compared with the whole treatment period. The number of days with
      missed medication was thus significantly higher for the evening dosing regimen.
      The difference in self-measured blood pressure between the two regimens was lost
      if the days with missed medication were removed from the statistical analysis.
      CONCLUSIONS: Time of once-a-day amlodipine administration does not influence its
      efficacy for 24-h blood pressure control. Furthermore, the use of self
      measurement and the MEMS may provide useful additional information on the
      pharmacodynamic impact of different dosing patterns in hypertensive patients.

PMID- 8133023
TI  - Continuous, non-invasive volume-clamp blood pressure: determinants of
      performance.
AB  - OBJECTIVE: To test a prototype hydraulic, non-invasive, continuous finger blood
      pressure monitor based on the volume-clamp principle for procedure-related
      factors likely to influence precision. DESIGN: The influence of these factors was
      determined by repeatability of finger blood pressure measurement and the
      relationship to contralateral arm-cuff blood pressure. METHODS: Repeated blood
      pressure measurements from three different fingers were made in 60 subjects
      following re-initialization of the device and re-insertion of the finger into the
      cuff. Repeatability was assessed in relation to simultaneous arm-cuff readings.
      Drift in arm-finger discrepancy was measured over a 1-h period. Finger diameter,
      drug therapy and presence of peripheral vascular disease were correlated with arm
      finger blood pressure difference. RESULTS: Repeatability coefficients (twice the
      SD of the arm-finger difference) across device re-initialization were large, but
      similar to parallel repeated arm blood pressure determinations: 17.6 and 17.1
      mmHg for systolic blood pressure (SBP) and 13.9 and 13.6 mmHg for diastolic blood
      pressure (DBP), respectively. Withdrawing and re-inserting the finger reduced
      repeatability substantially, with a 50% increase in repeatability coefficient. A
      trend towards a progressive 9-mmHg increase was observed in overestimation of SBP
      over the 1-h period. Mean +/- SD pooled arm-finger blood pressure differences
      were -10.8 +/- 14.6 mmHg for SBP and 4.5 +/- 9.4 mmHg for DBP. Blood pressure
      measured in different fingers was similar on average, with repeatability no
      poorer than for re-insertion of the same finger. The presence of peripheral
      vascular disease in 15 subjects correlated with a smaller arm-finger difference
      for DBP. CONCLUSIONS: Variations in positioning of the finger within the cuff
      influences blood pressure measurement during volume-clamp plethysmography,
      reducing its precision. Finger SBP exceeds brachial auscultatory readings and has
      similar precision.

PMID- 8133024
TI  - Sleep quality and continuous, non-invasive beat-to-beat blood pressure recording.
AB  - OBJECTIVE: To investigate the effects of continuous, non-invasive, beat-to-beat
      finger blood pressure monitoring on sleep in healthy men. DESIGN: After 1 night
      of habituation to the laboratory environment, which consisted of the placement of
      electroencephalographic equipment without recording, polygraphic sleep recordings
      were performed during two consecutive nights (nights 1 and 2) in 15 healthy men
      (mean +/- SD age 25 +/- 6 years). Blood pressure was recorded continuously for 24
      h from the end of night 1 to the end of night 2. RESULTS: The blood pressure
      recording procedure caused a decrease in the amount of rapid eye movement (REM)
      sleep and increased the duration of nocturnal awakenings. Consequently, sleep
      efficiency was decreased by approximately 5%. The blood pressure measurements did
      not affect the duration of light and of deep sleep. Although the respective
      predominance of deep sleep and of REM sleep at the beginning and at the end of
      the sleep period were preserved during the night of blood pressure recording, the
      blood pressure recording procedure hampered the rise in REM sleep during the
      final two thirds of the sleep period. CONCLUSION: In healthy young men
      continuous, non-invasive, beat-to-beat finger blood pressure monitoring induced
      modest reductions in sleep efficiency of similar magnitude to those observed
      previously with non-invasive ambulatory blood pressure monitoring.

PMID- 8133025
TI  - Comparison of classification of the severity of hypertension by blood pressure
      level and by World Health Organization criteria in the prediction of concurrent
      cardiac abnormalities and subsequent complications in essential hypertension.
AB  - OBJECTIVE: To determine whether classification of the severity of hypertension
      according to the World Health Organization (WHO) system, which utilizes
      additional clinical and laboratory findings, is superior to classification by
      blood pressure level alone in predicting prognostically important cardiac
      structural abnormalities and the risk of subsequent complications in asymptomatic
      subjects. DESIGN: Two-hundred and twenty adults with uncomplicated essential
      hypertension underwent baseline clinical evaluation and echocardiography; 88%
      were subsequently followed for a mean of 11.6 years. SETTING: University
      hospital. RESULTS: Left ventricular mass index and relative wall thickness were
      slightly greater in patients in the highest diastolic or systolic blood pressure
      stratum than in WHO stage II hypertensives, but these results were statistically
      non-significant. High peripheral resistance index was best identified by
      diastolic blood pressure level. Receiver operating characteristic curve analysis
      showed that all three methods had similar test performance in predicting abnormal
      left ventricular mass index, left ventricular geometry, relative wall thickness
      and peripheral resistance. During follow-up the proportion of patients who had a
      clinical event or died increased with increasing severity stratum in all three
      clinical classification systems, but the trends were statistically non
      significant. Risk stratification by echocardiographic left ventricular mass index
      was most successful in identifying patients at very high and very low risk of
      subsequent morbid events and all-cause mortality. CONCLUSION: Classification of
      hypertension severity by blood pressure level has similar, although limited,
      effectiveness at a lower cost than the WHO criteria in identifying patients with
      adverse cardiac changes and an impaired long-term prognosis. Echocardiographic
      measurement of left ventricular mass index was more successful than other
      classifications in predicting subsequent morbid events.

PMID- 8133026
TI  - Characteristics of a community-based distribution of home blood pressure in
      Ohasama in northern Japan.
AB  - OBJECTIVE: To evaluate the distribution, reference values and day-to-day
      variation of blood pressure of untreated subjects measured at home. DESIGN: Cross
      sectional study of a cohort. SETTING: General community in northern Japan.
      SUBJECTS: Blood pressure was measured in 871 subjects (mean +/- SD age 46.0 +/-
      19.5 years, range 7-98, constituting 38.7% of the local population of Uchikawama
      region, Ohasama) who were not receiving antihypertensive medication. METHODS:
      Subjects measured their own blood pressure at home at least three times (mean +/-
      SD 19.7 +/- 8.4) each morning using a semi-automatic oscillometric blood pressure
      measuring device. Screening blood pressure was measured once. MAIN OUTCOME
      MEASURES: Distribution of home blood pressure in the study population as a whole
      and with respect to age and sex, and the distribution of day-to-day variation of
      home blood pressure were determined. RESULTS: Mean home blood pressure was 117.3
      +/- 13.4/69.3 +/- 9.7 mmHg (95% confidence interval 116.4-118.2/68.7-70.0). The
      95th centile value was 143/85 mmHg, mean+SD 131/79 mmHg and mean + 2SD 144/89
      mmHg. Mean screening blood pressure was 126.2 +/- 18.9/72.1 +/- 11.7 mmHg (95th
      centile 159/92 mmHg). Age- and sex-specific 95th centile values as well as mean
      +/- SD were obtained. Mean+SD, mean + 2SD and the 95th centile values obtained as
      reference upper limits of home blood pressure from subjects identified as
      normotensive by screening blood pressure (n = 707) were 125/77, 137/86 and 134/83
      mmHg, respectively. Home blood pressure increased gradually with increasing age
      in both men and women, although blood pressure was significantly higher in men
      until 50 years of age. Day-to-day variation of home systolic blood pressure also
      increased with age. CONCLUSION: Since the distribution of home blood pressure
      values was affected by age and sex, age- and sex-matched reference values for
      home blood pressure should be established. Home blood pressure values in elderly
      subjects should be evaluated carefully, since these exhibit greater day-to-day
      variation.

PMID- 8133027
TI  - Development and antigen specificity of CD8+ cytotoxic T lymphocytes in beta 2
      microglobulin-negative, MHC class I-deficient mice in response to immunization
      with tumor cells.
AB  - beta 2-Microglobulin knockout mice (beta 2-m-/-) with MHC class I expression
      deficiency are able to develop functional TCR(+)-alpha beta, CD8+ CTLs in
      response to tumor cell injection. The i.p. injection of beta 2-m-/- mice with
      tumor results in the massive accumulation of highly lytic CD8+ CTLs in the
      peritoneum and causes the local recruitment of CD8+ T cells into lymph nodes and
      spleens of immune animals. The accumulation of CD8+ CTLs in peritoneum is
      accompanied by the rejection of tumor cells and the survival of animals. The
      deficiency in MHC class I expression in beta 2-m/- mice is reflected in the
      delayed tumor rejection and CD8+ cell accumulation during the primary anti-tumor
      response in comparison with normal mice. The secondary response, however, is
      identical in normal and MHC class I-deficient mice. The rejection of tumor cells
      appears to be MHC class I directed because no rejection of tumors, no
      accumulation of CD8+ CTLs, and no survival of animals were observed when
      syngeneic tumor cells were used for injection with the notable exception of anti
      minor Ag response. The Ag specificity of CD8+ CTLs in beta 2-m-/- mice is
      demonstrated using a panel of tumor target cells and class I transfectants.
      Although no substantial differences were found in the number and specificity of
      peritoneal CD8+ CTLs in beta 2-m-/- and normal mice using tumor rejection
      studies, the analysis of TCR-V beta phenotype using the panel of mAbs revealed
      the reduction in proportion of TCR-V beta 5 and TCR-V beta 6 used by CD8+ cell
      population from beta 2-m-/- mice. Development of lytic and H-2-directed CD8+
      cells in regional lymph nodes was also observed after footpad immunization of
      beta 2-m-/- mice with TNP-labeled C57BL/6 splenocytes, suggesting anti-minor Ag
      reaction.

PMID- 8133028
TI  - Fc gamma RII cross-linking inhibits anti-Ig-induced erg-1 and erg-2 expression in
      BCL1.
AB  - Activation of B cells through their Ag receptor is known to be negatively
      regulated by Fc gamma RII engagement. To explore the molecular and biochemical
      mechanisms of Fc gamma RII-mediated inhibition, we investigated the effect of Fc
      gamma RII engagement on the expression of two immediate-early genes, egr-1 and
      egr-2, and tyrosine phosphorylation events following the activation of the murine
      B cell line, BCL1. Egr-1 and egr-2 were expressed in BCL1 after slg cross
      linking. The induction of egr-1 and egr-2 expression was prevented when the Fc
      gamma RII was co-cross-linked with slg in BCL1, but not in WEHI-231. The
      inhibitory effects of Fc gamma RII engagement on egr-1 and egr-2 expression
      occurred when the Fc gamma RII was cross-linked with either slgM or slgD.
      Treatment with cyclosporin A prevented the expression of egr-2 induced by slg
      cross-linking, but did not inhibit egr-1 expression. In addition, cyclosporin A
      did not prevent the negative-regulatory effects of Fc gamma RII engagement on egr
      1 expression, suggesting that the Fc gamma RII works upstream from the site of
      action of cyclosporin A. To investigate activation signals more proximal to the
      plasma membrane, we compared tyrosine phosphorylation patterns of several
      effector molecules known to play a role in B cell activation. Cross-linking of
      slg induced tyrosine phosphorylation of the p62 GAP-associated protein. The p62
      protein became hyperphosphorylated in response to co-cross-linking of slg with Fc
      gamma RII. Our results identify egr-1 and egr-2 as targets of Fc gamma RII
      mediated inhibition of anti-Ig-induced B cell activation. In addition, they show
      that negative regulation by Fc gamma RII is effective in both cyclosporin A
      sensitive and insensitive pathways. Further, we suggest a possible Fc gamma RII
      signaling pathway leading to the inhibition of egr-1 and egr-2 expression.

PMID- 8133029
TI  - Tyrosine phosphorylation and activation of Vav GTP/GDP exchange activity in
      antigen receptor-triggered B cells.
AB  - Ag receptor triggering in B cells stimulates the activity of receptor-associated
      tyrosine protein kinases (TPK), leading to tyrosine phosphorylation of several
      cellular substrates, one of which is the Vav proto-oncogene product. We have
      recently determined that Vav is a TPK-regulated guanine nucleotide exchange
      factor for Ras in T cells. Here, we show that B cell extracts or Vav
      immunoprecipitates contain a Ras GDP/GTP exchange activity that is stimulated
      upon surface Ig (slg) triggering. The receptor-mediated stimulation of Vav
      exchange activity was blocked by the TPK antagonist, herbimycin A. Furthermore,
      immunodepletion of Vav from the B cell extracts removed approximately 80% of the
      Ras GDP/GTP exchange activity. These findings indicate, first, that B cell
      derived Vav possesses GDP/GTP exchange activity for Ras; second, that the
      exchange activity of Vav is accelerated by a slg-triggered, herbimycin A
      sensitive TPK and, third, that Vav accounts for most of the receptor-stimulated
      Ras GDP/GTP exchange activity. Thus, Vav may serve as a critical component in slg
      mediated signal transduction pathways by coupling receptor-associated TPK to the
      activation of Ras proteins.

PMID- 8133030
TI  - Regulation of CD23 expression by IL-4 and corticosteroid in human B lymphocytes.
      Altered response after EBV infection.
AB  - Cellular CD23 has been implicated in various biologic and pathologic processes.
      Here, we have studied the regulation of B cell CD23 expression and function by
      the synthetic corticosteroid, dexamethasone (DEX). We report that DEX acts
      directly on B lymphocytes to down-regulate IL-4-induced CD23 expression, whereas
      in parallel the IL-4R is up-regulated. Down-regulation of CD23 occurred at the
      cell surface and for shed material in culture medium. EBV infection of B cells is
      linked to development of lymphoproliferative diseases, including lymphoma, and
      there is evidence that EBV-stimulated CD23 expression may be instrumental in the
      inappropriate survival of infected cells. We have determined that treatment of
      EBV-infected cells with IL-4 leads to a synergistic up-regulation of B cell CD23.
      Furthermore, infection of B cells by EBV introduced a relative resistance to the
      down-regulatory effects of DEX on IL-4-induced CD23 expression.

PMID- 8133031
TI  - Transition from TCR-beta dimer to TCR-alpha beta-expressing cells by introduction
      of an alpha-chain in an immature thymocyte cell line.
AB  - The molecular basis for the surface expression of TCR-beta chain in the absence
      of association with TCR-alpha, -gamma, or -delta chain by an immature thymocyte
      cell line was investigated. The TCR-beta chain expressed by this cell line was
      not encoded by any unique DNA sequence, nor was it inserted into the membrane via
      a glycosyl-phosphatidylinositol linkage. Transfection of two other beta-chains
      derived from mature T cell clones resulted in the surface expression of dimers of
      the transfected beta-chains in both cases. Immunoprecipitation of the beta-dimer
      CD3 complex demonstrated that the association of the beta-dimer with the CD3
      complex, especially the CD3 zeta chain, was so weak that they dissociated under
      the detergent conditions in which the TCR-CD3 complex of mature T cells is kept
      intact. Transfection of TCR-alpha chain resulted in the expression of a TCR-alpha
      beta-CD3 complex and the disappearance of beta-dimers. In accordance with the
      changes in TCR complex components, the association between TCR-alpha beta and CD3
      complex became stable and the cells transduced signals more efficiently. The
      results demonstrate that the expression of TCR-beta as part of an incomplete TCR
      CD3 complex is developmentally regulated and the expression of TCR-alpha chain
      results in normal configuration and function of TCR complex.

PMID- 8133032
TI  - Evidence for a direct physical interaction of membrane IgM, IgD, and IgG with the
      B29 gene product.
AB  - The B cell Ag-receptor complex is composed of membrane immunoglobulin (mIg) and
      the mb-1/B29 heterodimer. In order to obtain insight into the architecture of the
      B cell receptor complex, we have looked for conditions that disrupt all disulfide
      bridges in the complex without affecting the noncovalent interaction between the
      mIg heavy chain and one or both members of the associated heterodimer. We show
      that in the presence of the reducing agent beta-mercaptoethanol the m mu, m
      delta, and m gamma heavy chains remain selectively associated with the B29
      members. Our findings implied that if isotype-related differences exist between
      the mIg-associated dimers, they may reside in B29 and not, as initially
      suggested, in mb-1. However, sequence analyses of B29 gene transcripts from B
      cells expressing mIgM, mIgD, or mIgG only revealed no differences in their
      nucleotide composition. Thus, in spite of their close physical interaction with
      mIg heavy chain classes, which are significantly distinct in the C-terminal
      regions, no isotype-specific forms of B29 seem to exist.

PMID- 8133033
TI  - Development and characterization of channel catfish long term B cell lines.
AB  - The establishment of channel catfish long term cloned B cell lines, the first
      such cell lines from ectothermic vertebrates, is described. These diploid cell
      lines were developed by in vitro LPS stimulation of B cells from normal channel
      catfish peripheral blood in the absence of overt attempts to transform or
      immortalize the cells. The resultant cell lines were cloned and maintained
      continuously in vitro for more than 12 mo without restimulation, feeder cells, or
      exogenous factors. Southern blot analyses of the parental cell lines revealed
      multiple mu-chain gene rearrangements, suggesting a polyclonal origin for the
      cell lines. Additional evidence for polyclonal development was provided by the
      demonstration that the parental cell lines transcribed mRNA for all of the six
      known channel catfish VH gene families. The characterization of several clonal
      cell lines revealed mRNA expression for both the secreted and membrane forms of
      the catfish mu-chain; however, the cloned cell lines each expressed only a single
      VH gene and analysis of the Ig H chain locus was consistent with allelic
      exclusion having occurred in these cells. Flow cytometry demonstrated that the
      cloned and uncloned cell lines produced both cytoplasmic and cell surface IgM.
      This IgM contained only one of the two L chain isotypes of the channel catfish,
      suggesting preferential L chain usage. Although these cells did not appear
      morphologically to be plasma cells, they secreted moderate levels of IgM in
      culture. These cell lines have considerable potential for addressing questions
      concerning the evolution of B cell function.

PMID- 8133034
TI  - IL-2 reverses human T cell unresponsiveness induced by thymic epithelium in SCID
      hu mice.
AB  - In this study we investigated the mechanism responsible for the unresponsiveness
      of thymus-reactive T cells obtained from severe combined immunodeficient (SCID)
      mice constructed with human fetal liver (FL) stem cells from donor A and an
      allogeneic human fetal thymus (FT) from donor B (A/B SCID-hu mice). These A/B
      SCID-hu mice have a human thymus containing B cells, macrophages, and dendritic
      cells from FL donor A but thymic epithelial cells from FT donor B. The repertoire
      of human T cells developing in this chimeric thymus is depleted of T cells
      specific for the HLA Ags of the FL donor, whereas T cells reactive against the
      HLA Ags expressed by the FT donor are still present. However, these thymocytes
      failed to proliferate and expressed low levels of the activation markers CD25,
      CD71, and HLA-DR after stimulation with the EBV-LCL of the FT donor in primary
      MLRs. This unresponsiveness could be completely reversed by IL-2. Restoration of
      T cell responsiveness was Ag specific and a unique property of IL-2. The T cells
      produced very low levels of IL-2 when stimulated with the HLA Ags of FT donor B,
      whereas they secreted normal levels of IL-2 after activation by third party
      alloantigens. Low IL-2 production was also observed at the clonal level. CD4+ T
      cell clones from A/B SCID-hu mice, specific for the HLA Ags of B, produced
      significantly less IL-2 and granulocyte macrophage-CSF than control CD4+ T cell
      clones. However, these T cell clones synthesized normal levels of IL-2 and
      granulocyte macrophage-CSF after stimulation with combinations of PMA/Calo or
      PMA/anti-CD3 mAb. Thus, T cells that differentiate in a chimeric thymus
      containing allogeneic host thymic epithelium are rendered tolerant to the HLA Ags
      expressed by the thymic epithelial cells. This tolerance results in the presence
      of T cells that do not proliferate properly after Ag-specific stimulation. This
      lack of proliferation is primarily related to their inability to produce
      sufficient levels of IL-2 and can be restored by exogenous IL-2.

PMID- 8133035
TI  - Repertoire diversity of antibody response to bacterial antigens in aged mice. IV.
      Study of VH and VL gene utilization in splenic antibody foci by in situ
      hybridization.
AB  - Mouse Abs against a bacterial epitope, the phosphorylcholine (PC) hapten are
      encoded by the T15 genes VH1(S107) and V kappa 22. It has been shown that PC
      specific hybridomas from aged animals often express IgV gene families other than
      T15. To determine the extent of this age-dependent molecular shift in the anti-PC
      response, we examined antibody-forming cells (AFC) in individual young (2 to 4
      month) and aged (20 to 24 month) mice by an in situ RNA hybridization. Mice were
      immunized either with PC coupled to keyhole limpet hemocyanin or with a
      Streptococcus pneumoniae strain R36a vaccine. Frozen splenic sections were
      prepared, and the clusters of PC-specific AFC (i.e., antibody foci) were
      identified by immunocytochemical staining. The adjacent splenic sections were
      hybridized with digoxigenin-labeled VH1(S107) and V kappa 22 DNA probes and with
      a C mu DNA probe as a control. The splenic sections were examined for 1) the
      number of Ab foci hybridized with the T15 probes, and 2) the estimated proportion
      of VH1+ and V kappa 22+ AFC within each focus. The results were comparable
      regardless of the form of PC Ag administered. Virtually all Ab foci (> 85%) in
      young mice hybridized with the T15 probes and were occupied by the VH1+/V kappa
      22+ AFC. In aged mice, the fraction of PC-binding Ab foci that hybridized with a
      given T15 probe varied from 35% to > 85%; T15+ AFC always represented a minor
      population of the focus (< 50%), the remaining PC-specific AFC being C mu + but
      T15-. Also, there appeared to be a greater loss of the V kappa 22 expression
      relative to the VH1(S107). Thus it appears that the T15+, PC-reactive B cells in
      aged mice responded to the Ag but that they could not dominate the response. The
      possibility of an intrinsic molecular change in the aging B cells in discussed.

PMID- 8133036
TI  - Properties of a novel gene isolated from a Hodgkin's disease cell line that is
      expressed early during lymphoid cell activation.
AB  - We have isolated a novel 667-bp cDNA clone, designated epag, from a Hodgkin's
      disease cell line-derived library that is expressed in association with T cell
      activation and which is not related to any known gene family. By using reverse
      transcription/PCR, we have demonstrated that epag mRNA is expressed as early as 1
      h after stimulation of normal PBMCs with anti-CD3. The levels of mRNA peaked by 4
      h, and no expression was detectable by 12 h postactivation or in resting cells
      incubated in culture without activation. Expression of epag was also detected in
      PMA- and PHA-stimulated, but not in nonstimulated Jurkat cells, and overall its
      expression in transformed cell lines of hemopoietic origin is highly restricted.
      Sequence analysis of multiple independent cDNA clones showed that epag expressed
      in the Hodgkin's-disease cell line L428 is identical to the gene expressed in
      normal activated PBMC. Epag expression was detected by reverse transcription/PCR
      in RNA preparations made from various normal nonlymphoid tissues. Computer
      analysis of the sequence identified an open reading frame encoding a putative
      protein of 13.2 kDa initiating at a CUG translational codon. In vitro translation
      and Western blot analysis with anti-peptide serum supported this analysis. We
      hypothesize that epag functions as an early signal that helps mediate the
      activation of T cells.

PMID- 8133037
TI  - A molecular biologic approach to study the fine specificity of antibodies
      directed to the MN human blood group antigens.
AB  - The human MN blood group Ags on glycophorin A are linear complex glycopeptide Ags
      determined by a combination of amino acid polymorphisms and O-glycans. M Ag has
      Ser and Gly, and N Ag has Leu and Glu, at positions 1 and 5, respectively. Amino
      acids 2 to 4 are O-glycosylated. To analyze the fine specificity of Abs
      recognizing these Ags, recombinant glycophorin A molecules were expressed in
      Chinese hamster ovary (CHO) cells. The M-allele cDNA was used to generate the N
      allele by site-directed mutagenesis. Two chimeric mutants were similarly
      constructed: Gly5-->Glu mimics the rare Mc phenotype; Ser1-->Leu is not found in
      human populations. Each type of glycophorin A was transfected into wild type CHO
      cells. In addition, the M-allele was expressed by mutant CHO cells defective in
      sialylation. The binding of M and N Abs and an anti-N lectin to recombinant
      glycophorin A was assessed by various methods. Two anti-N mouse mAbs and the anti
      N lectin required leucine at position 1, whereas Glu5 was not essential. One anti
      M mAb required both Gly5 and sialic acid. Three human anti-M sera required Ser1,
      whereas Gly5 was not essential. Four anti-M and -N mouse mAbs failed to bind
      recombinant glycophorin A, probably due to undersialylation of the recombinant
      glycoprotein. These results show that CHO cells expressing glycophorin A
      molecules varying in amino acid sequence and carbohydrate composition are useful
      for studying the fine specificity of Ab and lectin interactions with this
      glycoprotein. This is a novel approach and model system for investigating the
      immune response to linear complex glycopeptide Ags, a class of Ags that has
      received little attention previously.

PMID- 8133038
TI  - Mechanistic and selective constraints act on the establishment of V lambda J
      lambda junctions in the B cell repertoire.
AB  - Only four different subtypes of lambda Ig chains have been described in the
      mouse: lambda 1, lambda 2(V2), lambda 2(Vx), and lambda 3. These chains are
      encoded by gene segments all sequenced and well localized in chromosome 16.
      Although the lambda Ig system is both simple and well characterized, no
      exhaustive analysis has been done concerning V lambda J lambda junctions in
      nonintentionally stimulated B cells. To get an insight into the lambda B cell
      repertoire, we analyzed a large number of V lambda J lambda rearrangements
      isolated from spleen mRNA or genomic DNA of unimmunized adult BALB/c mice. By PCR
      amplification, more than 160 clones were obtained covering all V lambda J lambda
      recombinations. Simple recombinations of trimmed gene segments explain most
      sequences. Certain junctions have been found to be prevalent in each subtype, and
      an analysis of V lambda J lambda recombination sites shows that the splenic
      lambda repertoire can result from both differential efficiencies of rearrangement
      and selective processes.

PMID- 8133039
TI  - Genomic organization and chromosomal localization of the T-cell antigen 4-1BB.
AB  - 4-1BB is an inducible T cell surface receptor which belongs to the nerve growth
      factor receptor superfamily, a group of cysteine-rich cell-surface proteins. 4
      1BB is a 30-kDa glycoprotein and exists as both a monomer and a 55-kDa dimer on
      the T cell surface. Cross-linking 4-1BB with monoclonal antibody resulted in the
      2- to 10-fold enhancement of T cell proliferation. We have isolated and
      characterized 4-1BB genomic clones and have found that the 4-1BB gene contains
      two different 5' untranslated regions, which are used alternately to form the 4
      1BB mRNA. The two 5' UTRs were encoded in the same chromosome and were separated
      from one another by an intron of approximately 2.5 kb. The entire gene spans
      approximately 13 kb of mouse chromosome 4. 4-1BB gene consists of 10 exons and 9
      introns, in which there are two exons for 5' untranslated regions and 8 exons for
      coding region. Most of the putative functional domains were encoded by separate
      exons. 4-1BB extracellular domain contains four potential C6 (CXn C XX C XX CXn C
      Xn C) motifs, of which the first motif is partial and the third is distinct from
      those of nerve growth factor receptor or TNF receptor 1. A comparison of exon
      intron organization among the genes of the nerve growth factor receptor family
      indicated that most C6 motif is interrupted by an intron.

PMID- 8133040
TI  - Regulation of IFN-gamma-induced nuclear expression of IFN consensus sequence
      binding protein in murine peritoneal macrophages.
AB  - IFNs are well characterized macrophage-activating agents. Their varied effects
      are largely mediated via the induction of many genes, whose products act in
      concert to induce macrophage differentiation. Homologous DNA sequences have been
      found upstream of the promoter in many of these IFN-inducible genes and bind a
      family of trans-acting proteins. Interferon consensus sequence binding protein
      (ICSBP) is one member of this family of interferon regulatory factors (IRF) and
      is structurally related within the DNA-binding domain to the other members, IRF
      1, IRF-2, and ISGF3 gamma. ISCBP mRNA levels become elevated in response to IFN
      gamma; however, little is known about the regulation of ICSBP expression at the
      protein level. In this study, anti-ICSBP peptide Abs were used to quantify and
      localize ICSBP in murine peritoneal exudate macrophages. Western blot analysis of
      cytoplasmic and nuclear extracts from treated and control cells revealed ICSBP to
      be induced by IFN-gamma and not by IFN-alpha and to exist primarily in the
      nucleus. The regulation of ICSBP induction by IFN-gamma was consistent with the
      characteristics found at the mRNA level; inhibition by IFN-alpha or
      glucocorticoids and the requirement for protein kinase C (as determined
      pharmacologically). The time course of IFN-gamma-induced ICSBP showed an
      induction of protein that required approximately 12 h to reach maximal levels.
      Induced ICSBP was relatively stable, exhibiting a half-life of approximately 48
      h. Indirect immunofluorescence also demonstrated ICSBP to be an IFN-gamma
      inducible protein that is strongly localized to the nucleus.

PMID- 8133041
TI  - Self peptides isolated from MHC glycoproteins of non-obese diabetic mice.
AB  - The non-obese diabetic (NOD) mouse spontaneously develops an insulin-dependent
      diabetes mellitus that resembles human type I diabetes. This disease can be
      transferred by purified T cells or cloned T cell lines, implicating an autoimmune
      T cell attack on the pancreatic beta cells of the islets of Langerhans. As all T
      cell responses involve recognition of peptides bound to MHC molecules displayed
      at the cell surface, we have examined self peptides binding to the MHC molecules
      on spleen cells of the NOD mouse. Peptides eluted from the MHC class I molecule
      Kd have sequences that conform to known motifs for peptides binding this molecule
      in other strains of mice. The NOD mouse expresses the unique MHC class II
      molecule I-Ag7. Peptides eluted from I-Ag7 have sequences that implicate an
      acidic residue in the C terminus of the peptide as important for binding. The
      role of this residue in binding has been confirmed by direct peptide-binding
      analysis. This C-terminal acidic amino acid may interact with an arginine residue
      in the MHC class II alpha-chain that is exposed when beta-chain residue 57 is
      mutated to serine, or to the unique beta-chain residue histidine 56. These data
      may provide valuable insights into the nature of autoantigenic peptides presented
      by NOD mouse MHC molecules by defining the nature of I-Ag7-peptide binding.

PMID- 8133042
TI  - Purification and cloning of a novel serine protease, RNK-Tryp-2, from the
      granules of a rat NK cell leukemia.
AB  - We have biochemically purified a 27-kDa serine protease (designated RNK-Tryp-2)
      from the granules of the rat large granular lymphocyte leukemia cell line (RNK
      16) which has tryptase activity. Utilizing molecular sieve chromatography and
      reverse-phase HPLC, we purified RNK-Tryp-2 to homogeneity and sequenced 33 NH2
      terminal amino acids. Oligonucleotide primers were used in the PCR to generate a
      528-bp cDNA clone encoding a novel serine protease from RNK-16 mRNA. This cDNA
      clone was used to isolate an 884-bp RNK-Tryp-2 cDNA from an RNK-16 lambda-gt11
      library. The open reading frame predicts a mature protein of 233 amino acids
      which does not have potential sites for N-linked glycosylation. The cDNA encodes
      a leader peptide of at least 25 amino acids. The characteristic Ile-Ile-Gly-Gly
      amino acids of the N-terminus, and the His, Asp, and Ser amino acids that form
      the catalytic triad of serine proteases, are conserved. The amino acid sequence
      has less than 45% identity with any other member of the serine protease family,
      indicating that RNK-Tryp-2 is distinct protease. Southern blot analysis suggests
      the existence of one or more related genes. A single 1.3-kb mRNA transcript was
      detected by Northern blot analysis of total cellular RNA from the in vivo
      passaged RNK-16, rat splenocytes, lung and liver nonparenchymal cells, as well as
      in highly purified rat LGL and T cells. RNK-Tryp-2 is a novel serine protease
      that is expressed in the granules of large granular lymphocytes.

PMID- 8133043
TI  - Expansion and contraction of rhesus macaque DRB regions by duplication and
      deletion.
AB  - Previous sequence analysis of the rhesus macaque MHC (MhcMamu) class II DRB
      region has allowed the detection of at least 34 alleles belonging to different
      lineages. In this communication, 36 new Mamu-DRB alleles are reported. The gene
      content of the DRB region has been determined for several homozygous animals of
      consanguineous origin. As in other primates, the number of DRB genes present per
      haplotype is not constant, varying from two to six genes in rhesus macaques. Six
      major groups of DRB haplotypes have been defined in our rhesus macaque colony.
      Two haplotype groups were found to carry, as well as other Mamu-DRB genes, two
      genes that cluster into distinct HLA-DRB1 lineages. In one of these two groups, a
      haplotype harbors another two sets of DRB alleles that belong to the Mhc-DRB6 and
      -DRB*W6 lineages, respectively. Such a haplotype was probably generated by
      duplication, and our data suggest that after this particular expansion of the DR
      region, one of the duplicated Mamu-DRB6 alleles was the target of an Alu
      insertion. Although certain transspecies allelic lineages are evolutionarily
      stable, and have been conserved for at least 36 million years, the rhesus macaque
      class II haplotypes differ significantly from those found in humans, chimpanzees,
      and gorillas. Mhc-DRB regions are therefore comparatively unstable over longer
      evolutionary time spans, with regard to both the number of genes and the gene
      content, and must have been subjected to expansion and contraction.

PMID- 8133044
TI  - A 100-kDa protein in the C4-activating component of Ra-reactive factor is a new
      serine protease having module organization similar to C1r and C1s.
AB  - Ra-reactive factor (RaRF), a C-dependent bactericidal factor in mice, is composed
      of one polysaccharide-binding component and one C4/C2-activating component. The
      former is an oligomer of 28-kDa protein corresponding to the mannose-binding
      protein of mice. The 100-kDa protein, P100, has been shown to be present in the
      C4/C2-activating component. This protein generates 29- and 70-kDa polypeptide
      chains when reduced. In this study, we determined the nucleotide sequence of cDNA
      coding for P100. cDNAs were prepared by reverse transcription PCR and cassette
      ligation-mediated PCR on mRNA from BALB/c mouse liver, using primers synthesized
      by reference to the sequence determined in a previous study. The results of cDNA
      sequencing indicate that the precursor protein of P100 containing a 24-residue
      signal peptide consists of 704 amino acid residues. Taking the results of the
      previous electrophoretic study into consideration, it is thought that the
      cleavage of mature P100 protein generates a 29-kDa chain of 251 residues and a 70
      kDa chain of 429 residues. Although homology in the amino acid sequence of P100
      with that of human C1r and C1s subcomponents of C was less than 40%, a striking
      similarity in domain organization was found among these proteins, indicating that
      P100 is a new C4-activating serine protease structurally similar to C1r and C1s.
      Northern hybridization showed that the liver was the primary site of the
      expression of the P100 gene.

PMID- 8133045
TI  - Regulation of expression of the IL-1 receptor antagonist (IL-1ra) gene by
      products of the human cytomegalovirus immediate early genes.
AB  - Human cytomegalovirus (HCMV), which is a major cause of morbidity and mortality
      in immunosuppressed patients, can itself alter immune function. It has previously
      been shown that HCMV immediate early (IE) gene products regulate the IL-1 beta
      promoter. The purpose of these studies was to determine whether HCMV IE gene
      products regulate expression of the IL-1 receptor antagonist (IL-1ra) gene. THP-1
      cells, a myelomonocytic cell line, were transfected with a plasmid containing one
      or more of the HCMV IE genes downstream of the HCMV major immediate early
      promoter, or with a control plasmid. IL-1 beta and IL-1ra protein secretion was
      evaluated by ELISA, and expression of the mRNA for the cytokines was examined by
      means of Northern blot analysis. The HCMV IE1+2 gene products were found to
      increase expression of the mRNA for both IL-1 beta and IL-1ra; however, only the
      IL-1ra protein was released in increased amounts. The individual HCMV IE gene
      products had different effects on expression of the IL-1ra gene; the HCMV IE1
      gene product down-regulated expression of the IL-1ra gene, whereas the IE2 gene
      product up-regulated expression of the IL-1ra gene. Thus, HCMV IE gene products
      can either up-regulate or down-regulate expression of the IL-1ra gene, depending
      on which IE genes are expressed in monocytes-macrophages. This study adds to the
      understanding of how HCMV can alter immune function during both active and latent
      infection.

PMID- 8133046
TI  - Characterization of influenza A virus binding sites on human neutrophils.
AB  - Exposure of human neutrophils (PMN) to influenza A virus (IAV) triggers discrete
      responses in these cells that interfere with their normal host defense functions.
      Because the restricted host range and tissue specificities of many viruses are
      determined by cell surface molecules acting as virus receptors on target cells,
      it seemed plausible that IAV might interact with neutrophils via specific plasma
      membrane glycoproteins that bind to viral hemagglutinin. When the binding of
      intact IAV (ATCC strain A/PR/8/34 (H1N1)) to PMNs was examined by flow cytometry,
      virus binding was found to be saturable and to be diminished after extensive
      desialation of the cells with neuraminidase. Stimulation of PMNs with FMLP (0.1
      microM) caused a transient increase in IAV binding that was maximal (> 200%) at 2
      min after stimulation. When neutrophil membrane proteins were separated by gel
      electrophoresis and transferred to nitrocellulose, IAV bound selectively to two
      polypeptide bands of approximately 125 and 160 kDa. Relative binding to these two
      bands was modified and ultimately eliminated by treatment of PMN membrane
      proteins with neuraminidase before electrophoresis and blotting. Intact virus
      precipitated a limited number of proteins from solubilized PMN plasma membrane
      preparations, and Abs specific for sialophorin (CD43) recognized virus
      precipitated PMN membrane proteins of the same apparent m.w. as those detected in
      virus-membrane protein blots. These findings indicate that IAV binds to human
      PMNs through interactions with a limited number of PMN membrane glycoproteins,
      which include sialophorin (CD43).

PMID- 8133047
TI  - Bispecific anti-CD22/anti-CD3-ricin A chain immunotoxin is cytotoxic to Daudi
      lymphoma cells but not T cells in vitro and shows both A-chain-mediated and LAK-T
      mediated killing.
AB  - We have generated a bispecific anti-CD22/anti-CD3 immunotoxin (IT) and determined
      whether it would exert both lymphokine-activated killer (LAK) T cell-mediated and
      ricin A chain (dgA)-mediated toxicity to Daudi tumor cells but not to T cells in
      vitro. One parental IT, Fab'-anti-CD22-dgA makes a potent immunotoxin for B
      cells, but not T cells, while the other, Fab'-anti-CD3-dgA, kills neither T nor B
      cells. Three mouse quadromas were generated and the bispecific Abs (BsAbs) were
      purified by double affinity chromatography. Two of the three purified BsAbs
      induced significant proliferation and IL-2 production in T cells. All three BsAbs
      induced LAK-T cell-mediated specific lysis of CD22+ Daudi cells. Two of the
      purified Ab were conjugated to dgA. Using a 51Cr release assay in the presence of
      LAK-T cells and Daudi target cells, the IC50s of the BsAbs were 3.5 x 10(-10) M
      and 9 x 10(-11) M, as compared to 2.1 x 10(-11) M and 3.2 x 10(-11) M, for their
      respective ITs. Hence, in the presence of LAK-T cells, the BsITs were 3- to 17
      fold more cytotoxic than unconjugated BsAbs in 51Cr-release assays. Daudi cells
      were also treated in vitro with different mixtures of LAK-T cells, BsAbs, and
      BsITs and then adoptively transferred into SCID mice. As determined by the mean
      paralysis time of the recipients, in the presence of LAK-T cells the BsITs had
      impressive anti-tumor activity.

PMID- 8133048
TI  - In vitro and in vivo characterization of BR96 sFv-PE40. A single-chain
      immunotoxin fusion protein that cures human breast carcinoma xenografts in
      athymic mice and rats.
AB  - BR96 sFv-PE40 is a single-chain immunotoxin fusion protein targeted to the Ley
      Ag, which is expressed in many different human carcinomas as well as in normal
      gastrointestinal epithelium of humans and certain animals, including athymic rats
      but not mice. In vitro binding analysis determined that BR96 sFv-PE40 was similar
      in affinity to BR96 Fab. BR96 sFv-PE40 internalizes rapidly, similar to BR96 IgG.
      H3396 cells, derived from metastatic human breast carcinoma, have been
      established as tumor xenografts in estradiol-supplemented athymic mice and rats.
      H3396 tumor xenografts established in athymic mice (up to 350 mm3) and rats (up
      to 100 mm3) completely regressed after i.v. administration of BR96 sFv-PE40,
      given as 0.625 mg/kg (1.975 mg/m2) every 4th day for a total of five doses (mice)
      or 0.25 mg/kg (1.475 mg/m2) every 4th day for a total of four doses (rats). The
      tumors remained regressed for the duration of the study (> 85 days post-implant),
      which represents > 10 doubling times, indicating that the animals were cured.
      There was no toxicity in rats receiving a curative dose of 0.25 mg/kg, although
      liver and lung toxicity could be detected at a 16 times higher dose, 4 mg/kg or
      23.6 mg/m2. We conclude, therefore, that BR96 sFv-PE40 can cure tumor xenografts
      at well tolerated doses and also in the presence of Ley expression in normal
      tissues.

PMID- 8133049
TI  - The role of T cell activation in anti-CD3 x antitumor bispecific antibody
      therapy.
AB  - Anti-CD3 x antitumor bispecific Ab can retarget T cell mediated lysis in an MHC
      independent fashion and prevent tumor growth in animal models. Two bispecific Ab
      preparations that differ in the presence or absence of Fc were compared in the
      38C13 immunocompetent murine lymphoma model to evaluate how functional Fc and T
      cell activation impact on response to bispecific Ab therapy. Bispecific (bs) IgG
      contained functional Fc and was purified from hybrid-hybridoma Ab product.
      Bsf(ab')2 lacked functional Fc, and was genetically constructed using the leucine
      zipper technique. In vitro, bsF(ab')2 induced tumor cell lysis by activated T
      cells more effectively than bsIgG. However, bsF(ab')2 failed to induce T cell
      activation in the absence of tumor cells, and did so more slowly than bsIgG when
      tumor cells were present. In vivo, bsIgG induced nonspecific T cell activation
      whereas bsF(ab')2 did not. In therapy experiments, bsIgG inhibited tumor growth
      in mice although a single dose of bsF(ab')2 had minimal antitumor effect.
      BsF(ab')2 was capable of preventing tumor growth and improving survival when mice
      were also treated with T cell activators (IL-2 or staphylococcal enterotoxin B),
      or given repeated bsF(ab')2 doses. We conclude that therapeutic response to
      bispecific Ab was not dependent on functional Fc, but did require T cell
      activation. The use of bifunctional constructs that lack functional Fc therefore
      allows for separate manipulation of T cell retargeting and T cell activation and
      deserves further evaluation as a potential immunotherapy for malignancy.

PMID- 8133050
TI  - Association of HER2/neu expression with sensitivity to tumor-specific CTL in
      human ovarian cancer.
AB  - To study potential sources of tumor-associated Ags in human ovarian cancer, we
      have established two ovarian tumor cell lines (OvS1 and OvA2) from two ovarian
      cancer patients, which express the cellular oncogene HER2/neu. Corresponding
      tumor infiltrating lymphocyte cultures have also been established and display an
      autologous tumor-specific pattern of cytotoxicity that is HLA-A2 restricted. To
      determine the potential relationship between HER2/neu expression and CTL-mediated
      cytolysis, we first established tumor cell clones from OvS1. These were
      categorized as high or low expressors of HER2/neu (cOvS1+ or cOvS1-,
      respectively), and cOvS1+ clones displayed a significantly higher sensitivity to
      CTL killing as compared with cOvS1- clones. To modulate the expression of
      HER2/neu, ovarian cancer cells were treated with IFN-gamma. After this exposure,
      HER2/neu expression was significantly decreased, whereas the expression of HLA
      Class I was significantly increased. Despite the increase in HLA Class I
      molecules on the cell surface, CTL-mediated cytolysis of both OvS1 and OvA2 was
      significantly decreased. IFN-gamma treated cOvS1+ clones displayed a similar
      decrease in sensitivity to CTL killing, whereas IFN-gamma treated cOvS1- clones
      displayed an increase or no change in sensitivity to CTL. To confirm this
      apparent association between HER2/neu expression and CTL recognition, melanoma
      tumor cell lines that were insensitive to ovarian tumor-specific CTL were
      transfected with the HER2/neu gene. An HLA-A2+ HER2/neu-transfected melanoma cell
      line was made sensitive to HLA-A2 restricted ovarian tumor-specific CTL but not
      to HLA-A2 unrestricted CTL, whereas an HLA-A2- HER2/neu-transfected melanoma
      remained insensitive to HLA-A2 restricted CTL. These results demonstrate that the
      sensitivity of ovarian epithelial tumor cells to CTL-mediated lysis is associated
      with the level of expression of HER2/neu, suggesting that this oncogene product
      may serve as a source of tumor-associated Ags or as an inducer of such peptides.
      This is the first time in a human tumor system that oncogene expression has been
      related to the induction of antigenicity. These results prompt us to approach new
      strategies for immunotherapy of cancer.

PMID- 8133051
TI  - Isolation and characterization of dendritic cells from mouse heart and kidney.
AB  - Dendritic cells (DC) are thought to be distributed throughout lymphoid and most
      nonlymphoid tissues. Single cell suspensions were prepared from mouse hearts and
      kidneys. Subsets of MHC class II-positive (Ia+) leukocytes from both sources
      expressed markers such as CDw32 Fc receptors, F4/80, and complement receptor type
      3 (CD11b/CD18). The capacity of these cells to initiate primary in vitro immune
      responses was assessed using oxidative mitogenesis and allogeneic mixed leukocyte
      responses. After fractionation by density centrifugation, cell sorting,
      immunomagnetic bead separation, or cell panning, the stimulatory activity of
      kidney cell suspensions was found to reside in the low density, Ia+ leukocyte
      fractions after overnight culture (day 1). In contrast, freshly isolated (day 0)
      cells had considerably less or no activity in these assays. However, depletion of
      Ia+ or CD45+ cells on day 0 followed by overnight culture removed the stimulatory
      activity on day 1. Therefore, day 0 kidney cells contain Ia+ leukocytes that can
      acquire or up-regulate their stimulatory activity during overnight culture.
      Similar observations were made for cells isolated from hearts, except that a
      population of uncharacterized nonleukocytes with stimulatory activity was
      detected on day 0 but not day 1. The phagocytic capacity of the leukocytes was
      then examined. Subsets of Ia+ cells phagocytosed zymosan, as shown by two-color
      flow cytometry and other immunofluorescence studies, and the zymosan-positive
      cells from kidney were able to initiate primary responses. Overall, these data
      demonstrate the existence of DC in kidneys and hearts, and suggest that in situ
      these cells resemble immature rather than mature DC.

PMID- 8133052
TI  - Differential cytokine expression in maternal blood and placenta during murine
      gestation.
AB  - To evaluate the influence of gestation on peripheral blood T cells, we measured
      the mRNA production of several cytokines (IL-2, IL-4, IL-10, IFN-gamma) and the
      p55 subunit of IL-2R at different time points in the blood of pregnant mice and
      in the placenta. This was made possible by the use of a new PCR technique that is
      precise and quantitative. Our results show that pregnancy induces profound
      changes in the expression of these genes in peripheral blood cells. During the
      first week of gestation, there is an increase in the levels of all the cytokines,
      followed by a state of immunodepression characterized by levels of cytokines
      below normal (nonpregnant mice). In the placenta low levels of IL-2 and IL-10 are
      detected. IFN-gamma mRNA production is higher than the blood IFN-gamma mRNA in
      the last week of pregnancy. However, the main difference is found for IL-4 mRNA
      expression where the placenta levels are 5- to 10-fold higher than the blood mRNA
      expression. We discuss these results in the context of the placenta as a
      privileged immune site, where IL-4, being the main cytokine, may play a major
      regulatory role.

PMID- 8133053
TI  - IL-1 and transforming growth factor-beta regulation of fibroblast-derived IL-11.
AB  - IL-11 and IL-6 are fibroblast-derived cytokines with overlapping biologic
      properties. To determine whether IL-11 and IL-6 are similarly regulated, we
      characterized the effects of rIL-1 and TGF-beta (beta 1 and beta 2) on human lung
      fibroblast IL-11 production and compared this regulation with that of IL-6.
      Unstimulated fibroblasts did not produce significant amounts of IL-11, whereas
      rIL-1 alpha and TGF-beta were dose-dependent stimulators of IL-11 protein
      production, mRNA accumulation, and gene transcription. rIL-1 alpha and TGF-beta
      also interacted in a synergistic fashion to further increase IL-11 protein
      production and mRNA accumulation. The effects of rIL-1 and TGF-beta individually
      were not altered by the cyclic nucleotide-dependent protein kinase inhibitor
      HA1004, protein kinase C (PKC) inhibition with staurosporine, or chronic phorbol
      ester preincubation, or the calmodulin antagonists W7 and TFP. The effects of rIL
      1 alpha and TGF-beta in combination were also unaltered by HA1004, staurosporine,
      and chronic phorbol ester exposure. A23187, however, did induce IL-11 mRNA
      accumulation and W7 and TFP did reverse the synergistic stimulation caused by rIL
      1 and TGF-beta in combination. In contrast with the regulation of IL-11, TGF-beta
      did not effectively stimulate IL-6 mRNA accumulation, rIL-1 alpha was a more
      potent stimulator of IL-6 than IL-11 production, and rIL-1-induced IL-6 mRNA
      accumulation was augmented by W7 and TFP. These studies demonstrate that: 1) rIL
      1, TGF-beta, and agents that increase intracellular calcium stimulate lung
      fibroblast IL-11; 2) the IL-11 stimulatory effects of rIL-1 and TGF-beta are, at
      least partially, transcriptionally mediated and are the result of signal
      transduction pathways that are largely PKC, cyclic nucleotide, and calmodulin
      independent; and 3) rIL-1 and TGF-beta interact in a synergistic fashion to
      further increase fibroblast IL-11 production and that this synergy is mediated by
      a largely PKC- and cyclic nucleotide-independent and calmodulin-dependent
      activation pathway. Importantly, they also demonstrate that rIL-1 and TGF-beta
      stimulate lung fibroblast IL-6 and IL-11 production via distinct and
      differentially regulatable activation pathways.

PMID- 8133054
TI  - Interaction between serum amyloid P component and C4b-binding protein associated
      with inhibition of factor I-mediated C4b degradation.
AB  - Serum amyloid P component (SAP) is a member of the pentraxin protein family.
      Although present in all types of amyloid deposits, it is also a normal
      constituent of blood and extravascular tissues. In blood, SAP forms a calcium
      dependent, noncovalent complex with C4b-binding protein (C4BP). C4BP regulates
      the classical complement pathway as it binds C4b and functions as cofactor in its
      degradation by factor I. Although SAP and C4b bind to distinct sites on C4BP, it
      is not known whether the SAP-C4BP interaction affects the function of C4BP. We
      report that in a fluid phase system, SAP inhibited degradation of C4(H2O) (which
      is C4b-like) in a dose-dependent manner. Phosphorylethanolamine was found to
      alleviate the inhibitory effect of SAP on C4(H2O) degradation. Because this
      compound is known to inhibit the SAP-C4BP interaction, this indicated direct
      binding of SAP to C4BP to be required for inhibition of C4(H2O) degradation. Even
      though C4BP, C4(H2O), and SAP form a multimolecular complex in fluid phase, SAP
      was found to inhibit binding of C4BP to immobilized C4(H2O). The inhibitory
      effect was calcium dependent and alleviated by phosphorylethanolamine. Heparin,
      which is known to inhibit the interaction between SAP and C4BP, was also found to
      counteract the inhibitory effect of SAP on C4BP binding to C4(H2O). However, the
      effect of heparin was biphasic because high concentrations of heparin directly
      inhibited binding of C4(H2O) to C4BP. The inhibition of C4BP function by SAP
      suggests that SAP may be involved in regulation of the classical complement
      pathway C3 convertase.

PMID- 8133055
TI  - Platelet-activating factor antagonist TCV-309 attenuates the induction of the
      cytokine network in experimental endotoxemia in chimpanzees.
AB  - Platelet-activating factor (PAF) has been postulated to play a role in the
      pathogenesis of sepsis. Additionally, in vitro studies have revealed tight
      interactions between PAF and the cytokine network, and PAF is considered to be an
      important stimulator of neutrophil functions. To assess the intermediate role of
      PAF in the induction of cytokines and neutrophil degranulation in endotoxemia in
      vivo, 12 healthy adult chimpanzees were i.v. injected with a bolus dose of
      Escherichia coli endotoxin (4 ng/kg); four animals received endotoxin alone,
      whereas the other chimpanzees were infused with the specific and potent PAF
      antagonist TCV-309 (bolus of 100 micrograms/kg, followed by either 100
      micrograms/kg/h (n = 4) or 500 micrograms/kg/h (n = 4) for 5 h). At both doses
      TCV-309 significantly inhibited the endotoxin-induced rise in cytokine levels.
      Peak TNF concentrations after injection of endotoxin alone were 366 +/- 96 pg/ml,
      vs 105 +/- 47 and 115 +/- 56 pg/ml after administration of endotoxin together
      with the lower or higher dose of TCV-309, respectively (p < 0.05). TCV-309 also
      reduced the appearance of soluble TNFRs. Maximal levels of the type I soluble
      TNFR were diminished from 2.53 +/- 0.27 ng/ml (endotoxin alone) to 1.69 +/- 0.36
      ng/ml (high dose TCV-309; p < 0.05); peak values of the type II soluble TNFR were
      diminished from 8.62 +/- 1.19 ng/ml to 5.76 +/- 0.92 ng/ml (p < 0.05).
      Furthermore, TCV-309 attenuated the endotoxin-induced release of IL-6 (160 +/- 82
      pg/ml after endotoxin alone, vs 63 +/- 30 pg/ml in the low dose TCV-309 group (p
      < 0.05) and 65 +/- 29 pg/ml in the high dose group (p = 0.07) as well as that of
      IL-8 (279 +/- 168, vs 71 +/- 15 and 46 +/- 17 pg/ml, respectively; both p <
      0.05). TCV-309 tended to reduce the endotoxin-provoked rise in serum IL-1R
      antagonist levels. In contrast, TCV-309 did not affect the neutrophilic
      leukocytosis elicited by endotoxin, nor did it inhibit endotoxin-induced
      neutrophil degranulation, as monitored by the plasma levels of elastase-alpha 1
      antitrypsin complexes. We conclude that PAF plays a role, either directly or
      indirectly, in the stimulation of the cytokine network and in the shedding of
      soluble TNFR in endotoxemia. PAF does not seem to be an important intermediate
      factor in endotoxin-induced neutrophilia or neutrophil degranulation.

PMID- 8133056
TI  - Cefdinir (CI-983), a new oral amino-2-thiazolyl cephalosporin, inhibits human
      neutrophil myeloperoxidase in the extracellular medium but not the phagolysosome.
AB  - Cefdinir, a new oral 2-amino-5-thiazolyl cephalosporin, inhibited the luminol
      amplified chemiluminescence (LACL) response of human neutrophils stimulated by
      PMA but not opsonized zymosan, in a concentration-dependent but not time
      dependent manner. The LACL response to opsonized zymosan in cytochalasin B
      treated neutrophils was, however, inhibited by cefdinir. Various cephalosporins,
      regardless of the presence of a 2-amino-5-thiazolyl moiety, did not significantly
      alter the neutrophil LACL response triggered by PMA and zymosan. The LACL
      response induced by the calcium ionophore A23187 and FMLP was also impaired by
      cefdinir, and this impairment was increased in cytochalasin B-treated
      neutrophils. Superoxide anion generation by neutrophils, measured in terms of
      lucigenin-amplified chemiluminescence and cytochrome c reduction, was not
      altered. Spontaneous and FMLP-induced neutrophil degranulation, assessed by
      lysozyme and beta-glucuronidase release, were not modified by cefdinir.
      Furthermore, cefdinir inhibited LACL generation in cell-free systems consisting
      of H2O2, NaI, and either horseradish peroxidase or a myeloperoxidase-containing
      neutrophil extract. Orthodianisidine oxidation in these two acellular systems was
      inhibited by cefdinir. Cefdinir did not alter neutrophil bacterial killing at
      concentrations that inhibited myeloperoxidase-containing neutrophil extract
      dependent reactions induced by soluble stimuli. Taken together, these data
      strongly suggest that cefdinir directly inhibits the activity of myeloperoxidase
      containing neutrophil extract released into the extracellular medium during
      neutrophil stimulation by soluble mediators, but has no effect on that released
      into the phagolysosome during phagocytosis. This unusual property of a member of
      the beta-lactam family could be of interest in modulating the exaggerated
      inflammatory process often associated with infectious diseases.

PMID- 8133057
TI  - Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2,
      TGF-beta 3) is mediated by fibronectin.
AB  - TGF-beta isoforms regulate numerous cellular functions including cell growth and
      differentiation, the cellular synthesis and secretion of extracellular matrix
      proteins, such as fibronectin (Fn), and the immune response. We have previously
      shown that TGF-beta 1 is the most potent chemoattractant described for human
      peripheral blood neutrophils (PMNs), suggesting that TGF-beta s may play a role
      in the recruitment of PMNs during the initial phase of the inflammatory response.
      In our current studies, we demonstrate that the maximal chemotactic response was
      attained near 40 fM for all mammalian TGF-beta isoforms. However, there was a
      statistically significant difference in migratory distance of the PMNs: TGF-beta
      2 (556 microM) > TGF-beta 3 (463 microM) > TGF-beta 1 (380 microM) (beta 2: beta
      3, p < or = 0.010; beta 3: beta 1, p < or = 0.04; beta 2: beta 1, p < or =
      0.0012). A mAb to the cell binding domain (CBD) of Fn inhibited the chemotactic
      response to TGF-beta 1 and TGF-beta 3 by 63% and to TGF-beta 2 by 70%, whereas
      the response to FMLP, a classic chemoattractant, was only inhibited by 18%. In
      contrast, a mAb to a C-terminal epitope of Fn did not retard migration (< 1.5%).
      The Arg-gly-Asp-ser tetrapeptide inhibited chemotaxis by approximately the same
      extent as the anti-CBD (52 to 83%). Furthermore, a mAb against the VLA-5 integrin
      (VLA-5; Fn receptor) also inhibited TGF-beta-induced chemotaxis. These results
      indicate that chemotaxis of PMNs in response to TGF-beta isoforms is mediated by
      the interaction of the Arg-gly-Asp-ser sequence in the CBD of Fn with an integrin
      on the PMN cell surface, primarily the VLA-5 integrin. TGF-beta isoforms also
      elicited the release of cellular Fn from PMNs; we observed a 2.3-fold increase in
      Fn (389 to 401 ng/ml) in the supernatants of TGF-beta-stimulated PMNs compared
      with unstimulated cells (173.6 ng/ml). The concentration of TGF-beta required to
      cause maximal release of Fn from PMNs (4000 fM) is a concentration at which TGF
      beta is no longer chemotactic, suggesting that PMNs only use Fn that is
      constitutively expressed for migration. At higher concentrations of TGF-beta, the
      Fn released may accumulate basal to the cell, ultimately retarding cellular
      migration and modulating the chemotactic response.

PMID- 8133058
TI  - Neutrophil-activating peptides NAP-2 and IL-8 bind to the same sites on
      neutrophils but interact in different ways. Discrepancies in binding affinities,
      receptor densities, and biologic effects.
AB  - IL-8 and the neutrophil-activating peptide 2 (NAP-2) are members of the chemokine
      family of host defense cytokines. Although IL-8 was shown to interact with two
      different high affinity receptors on polymorphonuclear neutrophil granulocytes
      (PMN), direct demonstration of specific binding sites for NAP-2 is difficult,
      because the NAP-2 molecule lacks iodinable side chains. Here we present a
      modified labeling procedure for the chemokine that does not affect its biologic
      activity. The 125I-labeled NAP-2 specifically bound to PMN with two different
      affinities (KD = 0.65 and 22.4 nM). We observed complete cross-competition of
      unlabeled IL-8 with 125I-labeled-NAP-2 and of unlabeled NAP-2 with 125I-labeled
      IL-8, indicating the absence of monospecific binding sites for either chemokine.
      However, in contrast to former work by others, the total number of accessible
      sites was considerably lower for NAP-2 (13,000/cell) than for IL-8 (59,000/cell).
      In addition, PMN prepared from heparinized blood expressed significantly more
      receptors for NAP-2 than cells prepared from citrated blood, whereas receptor
      numbers for IL-8 were unchanged. Desensitization experiments suggested a
      regulatory role for the NAP-2 high affinity site. Short-term priming of PMN with
      a nonstimulatory dose of NAP-2 (or MGSA) but not with IL-8 led to drastic down
      regulation of the subsequent degranulation response, challenged by higher dosages
      of NAP-2, MGSA, or IL-8. Reduced functional responsiveness of cells correlated
      with the rapid down-regulation and internalization of NAP-2 and IL-8 high
      affinity binding sites. Thus, our data indicate that chemokines could mediate by
      individual modes of interaction with common receptor's different biologic
      functions.

PMID- 8133059
TI  - C5a as a model for chemotactic factor-stimulated tyrosine phosphorylation in the
      human neutrophil.
AB  - Human neutrophils were exposed to the chemotactic factors C5a, FMLP, IL-8,
      leukotriene B4, and PAF, for 30 s, and subsequently analyzed for protein tyrosine
      phosphorylation by immunoblotting whole cell lysates with a polyclonal
      antiphosphotyrosine Ab. All chemotactic factors caused the rapid de novo tyrosine
      phosphorylation of a broad band of approximately 120 kDa and increased the
      phosphotyrosine content of several other proteins, including two with molecular
      masses of 60 and 56 kDa that were present in the unstimulated neutrophil.
      Tyrosine phosphorylation was evident as early as 10 s after stimulation and was
      maintained for 1 to 3 min before dephosphorylation occurred. The extent of
      tyrosine phosphorylation was dependent on the concentration of chemotactic
      factor, with stimulation observed at concentrations as low as 10 to 100 nM. To
      investigate the pathway used by chemotactic factors to transduce this signal,
      neutrophils were treated with PMA. PMA also stimulated tyrosine phosphorylation
      in the neutrophil but with a slower response time and a different pattern of
      affected proteins. Additional experiments suggested that tyrosine phosphorylation
      is involved in the regulation of the neutrophil respiratory burst because the
      tyrosine kinase inhibitor, herbimycin A, inhibited C5a-induced protein tyrosine
      phosphorylation and also prevented C5a- and FMLP-induced superoxide anion
      production. Herbimycin A also inhibited PMA-induced tyrosine phosphorylation and
      superoxide anion production. To confirm that the ability to stimulate tyrosine
      phosphorylation was intrinsic to the C5a receptor, tyrosine phosphorylation was
      examined in both undifferentiated U937 cells (C5a receptor negative) and cAMP
      differentiated U937 cells (C5a receptor positive). C5a induced tyrosine
      phosphorylation only in differentiated U937 cells. Analysis of the C5a receptor
      mRNA using the PCR confirmed its presence in differentiated and its absence in
      undifferentiated U937 cells. Therefore, C5a stimulates tyrosine phosphorylation
      via a receptor-mediated mechanism and U937 cells provide a system in which G
      coupled receptor-mediated tyrosine phosphorylation can be investigated.

PMID- 8133060
TI  - Functional and ligand binding specificity of the rabbit neutrophil IL-8 receptor.
AB  - IL-8 mediates migration and activation of neutrophils. This study describes the
      functional and ligand binding specificity of the human intercrine peptides IL-8,
      neutrophil-activating peptide 2 (NAP-2), melanoma growth stimulatory activity
      (GRO), and platelet factor 4 (PF4) to rabbit neutrophils and mammalian cell lines
      transfected with rabbit IL-8 receptor cDNA (F3R). Rabbit neutrophil membranes
      bound 125I-labeled IL-8 and 125I-labeled NAP-2 but did not bind 125I-labeled GRO
      or 125I-labeled PF4. Rabbit neutrophils mobilized intracellular Ca2+ in response
      to IL-8 and NAP-2 but not to GRO or PF4. Monkey kidney cells (COS-7) and hamster
      lung fibroblasts (CCL-39) were transiently and stably transfected with the rabbit
      neutrophil IL-8 receptor F3R cDNA. COS-7 cells transfected with F3R cDNA bound
      125I-labeled IL-8 but did not bind other IL-8-related peptides such as 125I
      labeled NAP-2, 125I-labeled GRO, or 125I-labeled PF4. Furthermore, bound 125I
      labeled IL-8 was only displaced by unlabeled IL-8 but not by unlabeled NAP-2, GRO
      alpha, or PF4. Consistent with this observation, stably transfected CCL 39 cells
      expressing F3R cDNA mobilized Ca2+ only in response to IL-8. We conclude that F3R
      cDNA encodes a functional IL-8 receptor isotype with strict ligand binding
      specificity for IL-8, that rabbit neutrophils do not bind human GRO alpha, and it
      is suggested that rabbit neutrophils contain in addition to the F3R protein
      another IL-8 receptor isotype with broad ligand specificity or a distinct NAP-2
      receptor.

PMID- 8133061
TI  - Simian immunodeficiency virus as a model for vaccination against HIV. Induction
      in rhesus macaques of GAG- or NEF-specific cytotoxic T lymphocytes by
      lipopeptides.
AB  - The protection against infection by HIV probably requires the induction of both
      neutralizing Abs and CTL responses. Vaccination by attenuated HIV is hardly
      acceptable and the use of viral genes inserted in recombinant living vectors
      needs further development, especially with respect to safety. The peptidic
      vaccination is a promising approach but free peptides are usually poorly
      immunogenic. Because potent immune responses have been obtained in mice with
      modified peptides such as lipopeptides, we have designed a study to assess the
      immunogenicity of lipopeptides in nonhuman primates. Seven lipopeptides were
      synthesized, derived from known immunogenic regions of the simian
      immunodeficiency virus (SIV) NEF and GAG proteins. Twelve rhesus macaques,
      randomly chosen and not selected on their MHC basis, were immunized
      subcutaneously with the seven lipopeptides in IFA. An MHC class I-restricted and
      CD(8+)-mediated CTL response has been observed in seven macaques directed against
      one or two of the synthetic immunizing peptides in each case. These CTLs were
      able to lyse autologous target cells infected with a recombinant vaccinia virus
      expressing the SIV nef or gag genes, suggesting that they recognized the
      naturally processed peptides. These activities are detectable in peripheral blood
      cells for at least 10 mo after the last immunization. Abs against the immunizing
      peptides have also been observed in all cases. This study demonstrates that
      lipopeptides can generate cytotoxic and humoral immune responses in a large
      number of unselected animals and this approach may thus be worth considering in
      the vaccination against HIV.

PMID- 8133062
TI  - Nebulized but not parenteral IFN-gamma decreases IgE production and normalizes
      airways function in a murine model of allergen sensitization.
AB  - An animal model of local allergen (airways) sensitization was employed to study
      the effects of rIFN-gamma administered by ultrasonic nebulization through the
      airways on IgE production and airways responsiveness. BALB/c mice exposed to
      aerosolized OVA daily for 10 days developed a predominant anti-OVA IgE response,
      immediate cutaneous reactivity to OVA, and increased airways responsiveness (AR).
      Mice were treated with rIFN-gamma, either systemically or locally via the
      airways, following different protocols; i.p. rIFN-gamma failed to modulate the
      course of OVA sensitization, although total IgE levels in the serum were
      decreased by 50%. Anti-OVA IgE levels remained elevated, immediate skin test
      responses to OVA persisted, and AR was increased. However, local treatment of the
      airways with nebulized rIFN-gamma caused a 66% decrease in serum anti-OVA IgE and
      a twofold rise in IgG2a levels. Cutaneous reactivity to OVA was reduced and AR
      was also normalized after nebulized rIFN-gamma. In contrast to the i.p. route,
      treatment with nebulized rIFN-gamma resulted in a reduction in the in vitro IgE
      production by lymphocytes in response to OVA and IL-4. The timing of treatment
      with nebulized rIFN-gamma was important in determining the immunomodulatory
      response. Treatment after day 7 of OVA exposure failed to modulate sensitization.
      Treatment regimens with nebulized rIFN-gamma that began before day 7 of OVA
      exposure were able to decrease anti-OVA IgE. Only treatment regimens that
      included 3 days of nebulized IFN-gamma before OVA sensitization caused a decrease
      in cutaneous reactivity and normalization of AR. The data demonstrate that both
      the route and timing of rIFN-gamma administration are critical factors in the
      immunomodulation of the immediate allergic response to allergen sensitization via
      the airways.

PMID- 8133063
TI  - Thyroglobulin-induced murine thyroiditis assessed by intrathyroidal T cell
      receptor sequencing.
AB  - Thyroid glands from CBA/J (H-2k) mice, with human thyroglobulin (Tg)-induced
      thyroiditis, were removed and total cellular RNA was prepared and reverse
      transcribed as target cDNA for PCRs to detect 17 murine T cell receptor (mTCR) V
      beta families. Southern analysis of the resulting PCR fragments showed a marked
      bias in the intrathyroidal expression of mTCR V beta gene families with only 10
      detectable V beta gene families of the 17 tested. Four Tg-specific CBA/J T cell
      lines also showed a biased use of mTCR V beta gene families with only 7 V beta
      gene families detected of the 17 tested. Sequence analysis showed evidence of
      oligoclonal expansion of the intrathyroidal T cell populations, and some of the
      CDR3 sequences found in the thyroid infiltrates were identical, or similar, to
      examples of the patterns of CDR3 sequences seen in the Tg-specific lines.
      Overall, however, there was marked N-D-N sequence variation in both the lines and
      thyroid infiltrates. These data indicated that 1) mTcR V gene analysis of intact
      thyroid tissue reflected the thyroid Ag-specific T cells infiltrating the thyroid
      gland; 2) confirmed the phenomenon of oligoclonal expansion in early thyroiditis;
      3) showed that certain V beta gene families may be overemployed in the T cell
      recognition of Tg in the context of H-2k; and 4) revealed, by the varied patterns
      of the CDR3 sequences, that the V gene itself may be more important in thyroid Ag
      recognition than N-D-N region motifs.

PMID- 8133064
TI  - Predominant TCR-alpha beta variable and joining gene expression by muscle
      infiltrating lymphocytes in the idiopathic inflammatory myopathies.
AB  - The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of
      diseases in which autoreactive T cells are thought to play a pathogenetic role.
      We have determined the pattern of TCR-alpha beta gene expression by muscle
      infiltrating lymphocytes within clinically and serologically defined groups of
      IIM patients. We utilized the PCR to study TCR V gene expression in muscle
      biopsies from nine polymyositis (PM) and eight dermatomyositis (DM) patients, all
      of whom had autoantibodies directed against histidyl-transfer RNA synthetase
      (anti-Jo-1 autoantibodies). While the TCR repertoire in DM patients was generally
      polyclonal, an oligoclonal profile characterized PM patients. Certain V gene
      families were predominantly expressed; V alpha 1 and V beta 6 gene families were
      detected in 82 and 91% of PM biopsies, respectively. TCR expression was
      characterized further by analyzing J gene usage from four PM patients expressing
      the V beta 6 gene. Sequence analysis of 40 independent recombinants (10 per
      patient) identified only seven V beta 6 clonotypes and restricted usage of the
      related J beta 2.1, -2.3, and -2.7 genes. These data, describing predominant TCR
      V and J gene usage by muscle-infiltrating lymphocytes in myositis patients,
      suggest that Ag-driven T cell responses may play a primary role in mediating some
      forms of the IIM.

PMID- 8133065
TI  - Nucleotide sequence analysis of natural and combinatorial anti-PDC-E2 antibodies
      in patients with primary biliary cirrhosis. Recapitulating immune selection with
      molecular biology.
AB  - We have analyzed at the nucleotide level the variable region gene sequences of
      five human mAbs and five recombinant Fab fragments derived from the mesenteric
      lymph nodes of patients with primary biliary cirrhosis. Both mAbs and Fabs were
      monospecific for dihydrolipoamide acetyltransferase, the E2 subunit of the
      pyruvate dehydrogenase complex, which has been shown to be the major autoantigen
      of primary biliary cirrhosis. We found that although the mAbs, mainly of the IgM
      isotype, were encoded by a diverse array of VH and VL gene segments either as
      direct copies of germline genes or somatically mutated, the recombinant IgG Fabs
      expressed clonally related heavy chains displaying a high number of somatic
      mutations that very likely occurred in the context of Ag selection. Combinatorial
      pairing of clonally related heavy chains with highly homologous light chains
      suggests that the IgG anti-pyruvate dehydrogenase complex repertoire of primary
      biliary cirrhosis patients is the result of the clonal expansion of a restricted
      set of B cells.

PMID- 8133066
TI  - Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by
      high dose fractionated total lymphoid irradiation and its prevention by
      inoculating normal T cells.
AB  - Ionizing radiation can functionally alter the immune system and break self
      tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid
      irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such
      as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the
      extent of lymphoid irradiation, and the genetic background of the mouse strains.
      Radiation-induced tissue damage is not the primary cause of the autoimmune
      disease because irradiation of the target organs alone failed to elicit the
      autoimmunity and shielding of the organs from irradiation was unable to prevent
      it. In contrast, irradiation of both the thymus and the peripheral lymphoid
      organs/tissues was required for efficient induction of autoimmune disease by TLI.
      TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1
      mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions
      (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively
      prevented the autoimmune development. Depletion of T cells from the inocula
      abrogated the preventive activity. CD4+ T cells mediated the autoimmune
      prevention but CD8+ T cells did not. CD4+ T cells also appeared to mediate the
      TLI-induced autoimmune disease because CD4+ T cells from disease-bearing TLI mice
      adoptively transferred the autoimmune disease to syngeneic naive mice. Taken
      together, these results indicate that high dose, fractionated ionizing radiation
      on the lymphoid organs/tissues can cause autoimmune disease by affecting the T
      cell immune system, rather than the target self-Ags, presumably by altering T
      cell-dependent control of self-reactive T cells.

PMID- 8133067
TI  - T cell receptor V beta 15 dominates the antiacetylcholine receptor response in
      Lewis rat T cell lines.
AB  - Ten Lewis rat T cell lines responsive to Torpedo californica acetylcholine
      receptor (AChR) were assayed for TCR V beta usage. All lines were CD4+, OX-22-,
      and exhibited reactivity to one or more AChR chains. Several different V beta s
      were expressed by these lines, but V beta 15 was dominant in 5 of 10 lines.
      Unique CDR3 sequences were observed among the 10 lines, although three of the V
      beta 15 rearrangements used J beta 1.4. These data suggest that V beta 15+ T
      cells are selected in the in vitro response to the antigenically complex AChR in
      the Lewis rat.

PMID- 8133068
TI  - Isolation and characterization of a human nonspecific suppressor factor from
      ascitic fluid of systemic lupus erythematosus. Evidence for a human counterpart
      of the monoclonal nonspecific suppressor factor and relationship to the T cell
      receptor alpha-chain.
AB  - The monoclonal nonspecific suppressor factor (MNSF) is a lymphokine produced by a
      murine T cell hybridoma capable of suppressing Ab production by LPS-stimulated B
      cells. The existence of a human counterpart of MNSF, designated as the human
      nonspecific suppressor factor (hNSF), was likely because the anti-MNSF mAb (MO6)
      recognizes a similar suppressive activity in supernatants of Con A-stimulated
      human PBMC. By using the MO6 mAb, we investigated the presence of hNSF in the
      ascitic fluid of a patient with SLE. A small amount of cross-reactive hNSF was
      isolated from concentrated ascitic fluid fractionated with the MO6-affinity
      column, and a specific anti-hNSF mAb (P2) was produced. The hNSF eluted from the
      P2-affinity column could suppress up to 80% of the PWM-induced IgG production of
      human PBMC in a dose-dependent manner, even when added in late culture periods.
      Moreover, hNSF could inhibit proliferation of PBMC triggered by either PWM or Con
      A, which also implies an effect on T cells. On SDS-PAGE, the isolated hNSF
      resolved as a single peak of about 66 kDa and probably represents an aggregate of
      hydrophobic subunits. On reverse-phase HPLC, the bioactivity could be recovered
      from a single peak at 18.3 min. The suppression of IgG production induced by hNSF
      could be partly neutralized by preincubation with an anti-TCR-alpha mAb, whereas
      an anti-TCR-beta did not have any effect. Anti-TCR-alpha could also directly bind
      to the isolated nNSF, demonstrating some serologic relationship, as has been
      reported for several Ag-specific suppressor systems.

PMID- 8133069
TI  - Immunoassay for functional human soluble interleukin-6 receptor in plasma based
      on ligand/receptor interactions.
AB  - Soluble forms of most cytokine receptors, able to bind effectively to their
      respective ligands, have now been described. A soluble interleukin-6-binding
      molecule derived from the gp80 component of the multichain IL-6 receptor can be
      detected in biological fluids, and can act as an agonist of IL-6 activity. The
      clinical significance of the soluble receptor levels still remains to be
      explored. We took advantage of the characterization of an anti-IL-6 monoclonal
      antibody and of an anti-IL-6R monoclonal antibody that both bound to IL-6/IL-6R
      complexes to design an immunometric assay for the measurement of soluble IL-6R
      complexed to IL-6. This reaction scheme was designated as ELIA (enzyme-ligand
      immunoassay). When exogeneous IL-6 was added in excess to an sIL-6R containing
      sample, all sIL-6R was present in a complexed form. Thus, the reaction scheme
      could also be used to determine total sIL-6R concentrations. A recombinant sIL-6R
      standard was prepared from the supernatant of murine thymoma cells transfected
      with a gene coding for an extracellular portion of the IL-6 receptor. The assay
      permitted the precise and reproducible measurement of sIL-6R in serum or plasma.
      This approach is of general relevance for the determination of soluble cytokine
      receptors in biological fluids, provided that adequate anti-cytokine and anti
      receptor antibodies are available.

PMID- 8133070
TI  - Development of a bispecific monoclonal antibody for use in molecular
      hybridisation.
AB  - A mouse hybrid hybridoma (tetradoma) was prepared by fusing hybridomas producing
      monoclonal antibody to acetyl-aminofluorene with hybridomas producing antibody
      against calf intestine alkaline phosphatase. The tetradoma line established
      secreted immunoglobulin manifesting parental and bispecific binding
      characteristics. Bispecific monoclonal antibody was purified and used for a one
      step immunodetection assay of non-radioactive DNA and RNA probes. The immunoassay
      developed was able to detect 5 pg DNA within 2 h and gave low background noise.

PMID- 8133071
TI  - Characterization of metabolically labelled antigen following immunoprecipitation
      with antibody bound on ELISA plates.
AB  - Immunoprecipitation is a powerful technique for the immunochemical
      characterization of antigens. In combination with sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) a number of features, e.g.,
      presence of antigen, rate of synthesis, relative molecular weight of the
      polypeptide chain or post-translational modifications can be determined. Four
      different steps are basically involved in the immunoprecipitation procedure: (1)
      metabolic labelling of the antigen by incubation of viable cells with a
      radioactive precursor, (2) harvesting of the labelled antigen from the cells by
      lysis or in the case of secretory proteins from the supernatant, (3) formation
      and (4) purification of antibody-antigen complexes. The last step relies on
      secondary agents which bind to the antibody.

PMID- 8133072
TI  - A method for isolating granulocytes from rabbit blood without causing activation.

PMID- 8133073
TI  - A reporter system using a flow cytometer to detect promoter/enhancer activity in
      lymphoid cell lines.
AB  - We have devised an experimental system using a flow cytometer to examine the
      promoter/enhancer activity of DNA fragments in human lymphoid cell lines. Murine
      CD8 alpha gene cDNA used as a reporter gene was inserted in the reporter
      constructs under the control of various promoter/enhancers. Furthermore, the
      Epstein-Barr virus (EBV) OriP, which supports a high transient expression, was
      also included in the reporter constructs. Cell lines expressing EBV nuclear
      antigen-1 (EBNA-1) were transfected with the reporter constructs by
      electroporation. The expression of the reporter gene was measured by a flow
      cytometric analysis. This experimental system is quite simple and may be
      especially useful for the analysis of transcriptional elements functioning in
      lymphocytes.

PMID- 8133074
TI  - Bovine colostrum ultrafiltrate: an effective supplement for the culture of mouse
      mouse hybridoma cells.
AB  - An ultrafiltrate fraction (UF) of bovine colostrum has been successfully used as
      a cell culture supplement for growth and monoclonal IgG antibody production of
      cultured mouse-mouse hybridomas derived from spleen cells. In this study we
      compared the ability of UF to support growth and antibody production of IgA
      hybridomas derived from Peyer's patch cells with that of an IgG hybridoma cell
      line. One IgG (LPC2) and two IgA hybridoma cell lines (RB3 and P2E7) were used as
      models. The optimal UF concentration for Ig production and cell growth for both
      the IgA hybridoma RB3 and the IgG hybridomas was 5-10%. Initial plating density
      was found to be a critical factor for IgA hybridoma cell growth: the IgA
      hybridomas required a seeding density of at least 70,000 cells/ml to grow
      compared to 15,000 IgG hybridoma cells/ml (Pakkanen et al., 1992). The addition
      of small amounts (up to 2%) of FBS in 10% UF supplemented medium did not enhance
      IgA production or cell growth. RB3 and LPC2 cells seeded at equal density and
      grown in 10% UF for 8 days attained maximum cell densities at 3-4 days that were
      58% (RB3) or 34% (LPC2) lower than those in 10% FBS, but the total amounts of
      monoclonal antibody produced were 73% and 83%, respectively, of that in 10% FBS.
      Thus, Ig production per cell was 22-27% higher in 10% UF than in 10% FBS.
      Hybridoma cells could be cultured for at least 5 weeks without any reduction in
      growth rates, if medium was partially but not completely replaced twice a week.
      This suggests that hybridoma cells maintained in UF supplemented medium secrete
      growth promoting factors. Cells maintained in UF for up to 5 weeks sustained
      similar monoclonal antibody production rates as in short term culture. These
      results show that UF can be used as an economical and effective hybridoma culture
      supplement for the production of both IgG and IgA antibodies.

PMID- 8133075
TI  - Immunoglobulin class switch of anti-ganglioside monoclonal antibody from IgM to
      IgG.
AB  - Ganglioside GM2, which is one of the major gangliosides expressed on cell surface
      of neuroectodermal-origin human tumors, has been focused on as a target molecule
      for passive immunotherapy. One of the problems in this area was that monoclonal
      antibodies (mAbs) raised against GM2 were of IgM class even if donors of B cells
      were varied in mouse, rat or human. We stimulated two kinds of mice hybridomas
      having membrane-bound anti-GM2 IgM on their surface with GM2 incorporated in
      synthetic liposomes in the presence of the mouse thymocytes to accelerate the
      class switch of immunoglobulins (Igs). After the stimulation, protein A-reactive
      clones were sorted out using a cell sorter. We finally isolated two class switch
      variants generating mouse IgG3, designated KM796 and KM750, from original
      hybridomas producing mouse IgM anti-GM2 mAbs, KM696 and KM697, respectively after
      over 20-time repetitions of the sorting. ELISA with 11 common gangliosides
      revealed that one of the variant, KM750, retained the same binding specificity to
      N-acetyl GM2 as that of the parental IgM, KM697. By ELISA using panel of anti
      idiotype (Id) mAbs to anti-GM2 mAbs, KM750 was shown to retain the parental KM697
      Id. Another variant KM796 almost lost its activity in purification process in
      acidic condition and changes in Id were suggested. In immunofluorescence assay,
      KM750 was confirmed to bind to GM2-expressing tumor cell lines. The class switch
      hybridoma has been stably cultured with the production of the IgG3-class mAb for
      more than 22 months.

PMID- 8133076
TI  - Receptor-mediated label-transfer assay (RELAY): a novel method for the detection
      of plasma tumor necrosis factor at attomolar concentrations.
AB  - We have exploited the extremely high binding specificity of the 55 kDa human
      tumor necrosis factor (TNF) receptor in an assay designed to detect TNF with
      sensitivity limited only by limits in the detection of 131I. Bivalent derivatives
      of the 55 kDa TNF receptor (referred to here as the TNF binding protein), in
      which the extracellular domain is coupled to an IgG heavy chain, ordinarily bind
      TNF with very high affinity as a result of the fact that they interact with two
      separate sites on the trimer surface. The TNF binding protein is radioiodinated
      to a high specific activity and then added to plasma at a saturating
      concentration, so that it binds all active TNF present in the solution. Covalent
      adducts between molecules of TNF and molecules of the binding protein are then
      produced by crosslinking with disuccinimidyl suberate (DSS). The complexes are
      swept out of solution using sepharose beads to which polyclonal anti-TNF
      antibodies have been affixed. On electrophoresis, the complex presents itself as
      a band of M(r) = 200 kDa (as distinct from the uncomplexed binding protein, which
      has a size of 120 kDa and which in any case is removed by washing). As little as
      50 fg of active TNF (600,000 trimers) can be detected in a 5 ml sample of plasma
      using this approach, corresponding to the detection of TNF at a 200 aM
      concentration. Notably, no TNF is detectable in normal plasma specimens,
      indicating that normal plasma contains active TNF at a concentration beneath 200
      aM.

PMID- 8133077
TI  - Localization of activin subunits in early murine development determined by
      subunit-specific antibodies.
AB  - Activins are thought to be involved in early differentiation processes during
      amphibian and avian development. Little is known, however, about the role of
      activins in early developmental stages of higher vertebrates. In order to study
      activin protein expression in early murine development we have prepared
      polyclonal antibodies against synthetic peptides corresponding to C-terminal
      sequences of the murine beta A and beta B activin subunits. Both antibodies
      recognized specifically activin A and activin B in different immunological assays
      including ELISA and immunoblotting. Using these antibodies in immunofluorescence
      experiments a good correlation between mRNA and protein expression of the beta
      subunits was observed in different in vitro model systems for early murine
      development. In addition, beta A and beta B subunit protein localization appeared
      to be different in 3.5- and 4.5-day mouse blastocysts. The results presented here
      are consistent with a role for different activin forms in the regulation of
      distinct processes in early murine development.

PMID- 8133078
TI  - A rapid and semi-quantitative method for the detection of autoantibodies by
      multiple spot immunoassay.
AB  - A method for rapid simultaneous determination of multiple autoantibodies in sera
      has been developed. 42 different antigens were coated onto a nitrocellulose
      membrane in a miniblotter apparatus with 42 lanes. The membrane was also coated
      with different concentrations of human IgG to create a standard curve. The
      blotting apparatus after coating, blocking and washing was turned 90 degrees so
      that all lanes crossed the antigen coated lanes. Thereafter, 42 sera were
      incubated with the antigens. After this stage the membrane was treated as in the
      usual dot-blot procedure. After incubation with alkaline phosphatase labelled
      anti-human IgG, staining and drying of the membrane, the staining intensity of
      individual lanes was scanned into a data file and analyzed by computer. By this
      method it was possible in 4 h to examine 42 sera for autoantibodies against 42
      antigens, i.e., more than 1600 tests. Furthermore, the amount of antibody could
      be semi-quantified, using the IgG standards. The method should be useful for
      rapid screening of autoantibodies in a routine laboratory.

PMID- 8133079
TI  - An in vitro test for endocytotic activation of murine epidermal Langerhans cells
      under the influence of contact allergens.
AB  - Several in vivo and in vitro studies have shown that contact sensitizing agents
      induce enhanced internalization of cell membrane constituents by epidermal
      Langerhans cells (LC). However the intracellular distribution of the internalized
      material has not yet been clearly defined. For this reason we investigated the
      uptake of gold-labeled antibodies against MHC class II molecules by cultured
      murine LC under the influence of various contact sensitizing agents, non
      sensitizing analogues, and irritants. Antigen-antibody complexes were visualized
      by light microscopy using the silver enhancement technique and by pre-embedding
      electron microscopy. Viability was monitored by staining dead cells with
      propidium iodide. For light-microscopic evaluation of the intracellular
      distribution pattern of gold particles, a stimulation index was defined and used
      for the assessment of endocytotic activation. Untreated and solvent treated
      (control) cells exhibited an accumulation of internalized gold complexes into
      large aggregates composed of few intracellular vesicles. Cytoplasmic staining was
      absent and few gold particles were detectable in the endocytotic organelles under
      these conditions. In contrast to the non-sensitizing compounds DCNB and DNBSO3,
      which had no effect at all, treatment with subtoxic concentrations of the contact
      sensitizing agents DNFB, DNCB, TNCB, K2Cr2O7, NISO4 and p-phenylenediamine
      resulted in diffuse intracellular staining which was most pronounced in the
      submembraneous region. This was due to the numerous endocytotic vesicles which
      were closely associated with the cell membrane. Consequently a significant
      increase in the stimulation index was noted for these compounds. An irritant such
      as sodium lauryl sulphate used in subtoxic concentrations did not influence the
      intracellular distribution of internalized gold particles whereas toxic amounts
      of this compound induced a diffuse intracellular staining pattern indicative of
      membrane destruction. This approach represents a practical and reliable test for
      endocytotic activation of murine LC and may be useful for in vitro tests of the
      activating and possibly sensitizing properties of new chemical compounds.

PMID- 8133080
TI  - Recombinant technology in the preparation of immunogen and enzymatic tracer.
      Application to the development of an enzyme immunoassay for rat prolactin.
AB  - A competitive enzyme immunoassay for rat prolactin using an immunogen and a
      tracer obtained by recombinant DNA technology is described. Polyclonal antibodies
      were raised in rabbits immunized with a purified chimeric protein consisting of
      rat prolactin fused with two synthetic immunoglobulin G binding domains derived
      from staphylococcal Protein A. The enzymatic tracer was obtained using an
      expression system which permits insertion of rPRL DNA sequence in the alkaline
      phosphatase gene. Antibodies and tracer were used to develop a solid-phase
      competitive immunoassay for the measurement of rat prolactin in plasma with a
      minimal detectable concentration of 0.5 ng/ml. The mean intra- and inter-assay
      coefficients of variation were 7.8 and 13.2%, respectively. Rat plasma
      concentrations measured with this assay correlated well with those obtained with
      a conventional enzyme immunoassay (r = 0.993, slope = 1.037, n = 24).

PMID- 8133081
TI  - The detection of intracytoplasmic interleukin-2 in Jurkat E6.1 and human
      peripheral blood mononuclear cells using direct conjugate, two-colour,
      immunofluorescent flow cytometry.
AB  - The most commonly used approaches for the estimation of cytokine protein
      production involve the quantification of cytokines produced, and accumulated, in
      a complex body fluid or supernatant of cultured cells, by means of a bioassay or
      immunoassay, but these techniques do not permit an estimation of the frequency or
      phenotype of cytokine-producing cells. Traditional methods use
      immunohistochemical based techniques which can be difficult to perform and
      interpret, whereas flow cytometry has the advantage of objective assessment and
      standardisation and is less labour intensive. In this study we have established a
      rapid and sensitive technique for the simultaneous detection of intracellular IL
      2 in conjunction with CD3. Polyclonal goat anti-IL-2 and control goat IgG were
      conjugated to FITC and then separated from free fluorochrome using column
      chromatography. PHA activated PBMC or Jurkat E6.1 cells were fixed in
      paraformaldehyde and permeabilised with saponin, followed by the addition of
      directly conjugated antibodies (FITC anti-IL-2 or PE anti-CD3) alone or in
      combination. Samples were then analysed using a flow cytometer and the percentage
      of dual labelled cells calculated. Several methods have been previously
      established for the detection of intracellular cytokines using flow cytometry and
      employing multiple layers of antibodies in the detection steps. By using direct
      conjugates the technique is less time consuming, requires fewer controls and can
      be used to examine cytokine production by identifiable cell phenotypes in a mixed
      cell population.

PMID- 8133082
TI  - The relative radioresistance of interleukin-2 production by human peripheral
      blood lymphocytes: consequences for the development of a new limiting dilution
      assay for the enumeration of helper T lymphocyte precursor frequencies.
AB  - We describe a limiting dilution assay for the enumeration of alloreactive helper
      T lymphocyte precursor frequencies in human peripheral blood. The proliferation
      rate of the murine indicator cell line, cytotoxic T lymphoblastic line 2 (CTLL-2)
      induced by interleukin-2 (IL-2) culture supernatants was determined by staining
      with the fluorescent DNA dye propidium-iodide. Lymphocytes from healthy
      individuals as well as from patients with end stage kidney disease and no
      previous allosensitization exhibited a relative radioresistance of their IL-2
      production up to gamma irradiation doses of 40-60 Gy. This differs from previous
      findings in the literature, showing a total inhibition of the IL-2 production in
      unsensitized individuals using a gamma irradiation dose of 20 Gy. The
      consequences of this relative radioresistance are that for a reliable stimulator
      cell inactivation in assays for the enumeration of helper T lymphocyte precursors
      gamma irradiation doses of at least 50 (-60) Gy are needed. Increasing the gamma
      irradiation dose for the inactivation of the stimulator cells can result in a
      decrease of the antigen presenting capacity of these cells.

PMID- 8133083
TI  - Solid versus liquid phase assays in detection of insulin antibodies. Influence of
      iodination site on labelled insulin binding.
AB  - On type 1 newly diagnosed and on insulin treated diabetic patients, anti-insulin
      autoantibodies (IAA) and antibodies (IA) having the same specificity are
      respectively induced. Such immune response may be evaluated either by
      radiobinding assay (RBA) or enzyme-linked immunosorbent assay (ELISA). Both
      methodologies have been compared at previous International Workshops, which
      pointed out discrepancies in results. In this work, IAA/IA prevalence was
      assessed by displacement RBA and ELISA, in normal subjects, type 2 (treated with
      hypoglycaemic agents), insulin treated and newly diagnosed type 1 diabetic
      patients. Results showed a lack of RBA-ELISA agreement. An attempt was then made
      to determine whether such results were, at least in part, attributable to
      iodination site in Tyr-A14. For this purpose parallel RBA assays were carried out
      by using radiolabelled insulin at A14 and A19 Tyr residues. Control sera and
      samples from insulin treated and type 1 newly diagnosed diabetic patients were
      tested. Our results suggest that labelling position is not involved in
      artifactual binding of tracers, at least as a systematic phenomenon. In the
      majority of cases the variability in RBA-ELISA signal ratios are best explained
      in terms of differences in the basic principles operating in both methods instead
      of artifacts due to tracer preparation.

PMID- 8133084
TI  - Rapid, activity-guided isolation of sex-limited protein (Slp) from mouse serum by
      fractionated precipitation and high-performance liquid chromatography.
AB  - We have recently demonstrated that sex-limited protein (Slp) plays a key role in
      an EDTA-resistant mouse complement activation pathway. A rapid procedure,
      utilizing classical chromatography methods on an FPLC system, was developed for
      the isolation of functionally active Slp. The method is based on the fractionated
      precipitation of serum by polyethylene glycol 6000, followed by heparin Sepharose
      Cl-6B affinity chromatography, Mono Q anion exchange and Superose 12 gel
      filtration. The isolation of Slp was monitored by a hemolytic assay. The
      procedure resulted in the purification of Slp, which by SDS-PAGE gave a single
      band of M(r) 2000,000 under non-reducing conditions, and under reducing
      conditions three bands corresponding to M(rs) of 105,000, 76,000 and 37,000.

PMID- 8133085
TI  - Serum p24 antigen level as an intermediate end point in clinical trials of
      zidovudine in people infected with human immunodeficiency virus type 1. Aids
      Clinical Trials Group Virology Laboratories.
AB  - Serum p24 antigen levels were examined in subjects from three clinical trials of
      zidovudine to determine whether the pattern of change in serum p24 antigen during
      the first 8-16 weeks of therapy was associated with human immunodeficiency virus
      type 1 (HIV-1) disease progression or death. Among 406 patients with AIDS and a
      first episode of Pneumocystis carinii pneumonia, 65% had measurable pretreatment
      concentrations of serum p24 antigen (> or = 10 pg/mL). Changes during treatment
      were not associated with reduced mortality. In 637 mildly symptomatic patients,
      24% had measurable concentrations, and changes were marginally associated with
      increased time until more advanced disease. Among 683 asymptomatic patients, 18%
      had measurable concentrations, and changes were not associated with increased
      time until progression. Despite the small number of clinical events and the low
      rate of serum p24 antigen positivity in the latter two studies, pretreatment
      serum p24 antigen levels were predictive of clinical outcome; subsequent
      measurements appear to be of limited use in evaluating zidovudine therapy.

PMID- 8133086
TI  - Combination therapy with zidovudine and didanosine selects for drug-resistant
      human immunodeficiency virus type 1 strains with unique patterns of pol gene
      mutations.
AB  - Drug resistance conferred by specific human immunodeficiency virus type 1 (HIV-1)
      pol gene mutations has been associated with clinical progression in HIV-infected
      patients receiving anti-retroviral therapy. This study examined drug
      susceptibilities and pol mutations of HIV-1 strains from patients treated for 1
      year with zidovudine, didanosine (ddI), or zidovudine and ddI. Ten (42%) of 24
      patients receiving combination therapy versus 8/26 (31%) receiving only
      zidovudine had HIV-1 strains with phenotypic zidovudine resistance or a
      zidovudine resistance pol mutation at codon 215 (P = .6). In contrast, a ddI
      resistance mutation at codon 74 was less common among patients receiving
      combination therapy (2/24) than among those receiving ddI only (17/26; P < .001).
      Two patients receiving combination therapy developed resistance to zidovudine and
      ddI; they had HIV strains with amino acid mutations at codons 62, 75, 77, 116,
      and 151. Combination therapy with zidovudine and ddI selects for zidovudine
      resistant HIV-1 strains lacking a ddI resistance mutation and for multidrug
      resistant strains containing novel pol mutations.

PMID- 8133087
TI  - Human immunodeficiency virus type 1 causes productive infection of macrophages in
      primary placental cell cultures.
AB  - To characterize the role of the placenta in vertical transmission of human
      immunodeficiency virus type 1 (HIV-1), the susceptibility of primary human
      placental cultures and of transformed trophoblast cell lines to infection by
      several HIV-1 isolates was examined. Placental cultures supported the replication
      of all strains tested, including lymphocyte-, macrophage-, and amphotropic
      isolates. All viruses replicated to modest levels, with production of both viral
      antigen and infectious virus in the culture supernatants. Placental cells
      demonstrated a pattern of permissiveness for HIV-1 isolates distinct from that
      seen with lymphocytes, blood-derived macrophages, or T cell lines.
      Immunofluorescent staining showed that 5%-10% of the cultured placental cells
      expressed viral antigens, and double labeling revealed that the HIV-positive
      cells were macrophages not trophoblasts. None of the trophoblast cell line (JEG
      3, Jar, BeWo, HP-W1) could be infected by HIV. These results support the
      hypothesis that infection of the placenta could play a role in maternofetal
      transmission of HIV-1 and suggest that the placental macrophage is likely to be
      the primary cell type responsible.

PMID- 8133088
TI  - Human T cell lymphotropic virus type I infection among female sex workers in
      Peru.
AB  - Four hundred female sex workers attending a sexually transmitted disease clinic
      in Lima, Peru, were interviewed for demographic information and medical,
      contraceptive, and sexual practice histories. Cervical cultures were done for
      Neisseria gonorrhoeae and Chlamydia trachomatis, and serum was tested for
      antibodies to human immunodeficiency virus, human T cell lymphotropic virus type
      I (HTLV-I), Treponema pallidum, C. trachomatis, herpes simplex virus type 2 (HSV
      2), and Haemophilus ducreyi. The prevalence of HTLV-I increased with duration of
      prostitution from 3.6% (< 3 years) to 9.3% (3-6 years) to 15.9% (> 6 years; P <
      .01). After adjustment for duration of prostitution, reduced risk of HTLV-I was
      significantly correlated with condom use for more than half of all sexual
      exposures for > 3 years (odds ratio [OR], 0.34; 95% confidence interval [CI],
      0.13-0.89). Further adjusting for condom use, HTLV-I seropositivity was
      associated with C. trachomatis (OR, 3.7; 95% CI, 1.4-13.2) and with antibody to
      HSV-2 (OR, 3.7; 95% CI, 0.5-29.6). Thus, duration of prostitution, lack of
      consistent condom use, and past infection with C. trachomatis were significantly
      associated with HTLV-I seropositivity.

PMID- 8133089
TI  - Persistent cytomegalovirus infection of semen increases risk of AIDS.
AB  - To evaluate if persistent cytomegalovirus (CMV) infection of semen in human
      immunodeficiency virus type 1 (HIV-1) antibody-positive men increases AIDS risk,
      serial cultures for CMV every 3-6 months were attempted four or more times from
      164 men followed 3 years. CMV was never isolated from 58 men, in 1 or 2 samples
      from 54 (intermittently positive), and in > or = 3 samples from 52 (persistently
      positive). The Cox model was used to estimate relative hazards while controlling
      for CD4 cell number. The relative hazard was 2.9 for those intermittently and 4.0
      for those persistently positive (P < .001). No Kaposi's sarcoma occurred in
      culture-negative men, 3 cases (5.6%) in intermittently positive men, and 4 cases
      (7.7%) in persistently positive men (P < .04). Persistent CMV in semen increases
      the hazard of AIDS in HIV-1 antibody-positive men, possibly by activating CD4
      cells to produce HIV-1. Thus, control of CMV in HIV-1-infected persons may slow
      progression to AIDS.

PMID- 8133090
TI  - Frequency distribution of cytomegalovirus envelope glycoprotein genotypes in bone
      marrow transplant recipients.
AB  - Using restriction analysis of polymerase chain reaction (PCR)-amplified DNA, the
      cytomegalovirus (CMV) envelope glycoprotein (gB and gH) genotypes were determined
      for virus isolates from 128 bone marrow transplant recipients with fatal or
      nonfatal CMV. All isolates could be assigned to one of four gB and gH genotypes
      previously identified by DNA sequencing studies. Isolates of gB type 1 were more
      commonly found to be of gH type 2, whereas gB types 2-4 were more commonly linked
      to gH type 1. A small frequency of recombination with gB was detected by
      restriction analysis of DNA from variable regions of the gp55 and gp116 domains.
      Multiple isolates from various sites of 29 patients were typed and, with three
      exceptions, the gB genotype remained constant in all isolates from a single
      patient. Patients who survived CMV infection more commonly shed virus of gB type
      1 than those who died (P = .003). This significant difference of gB types among
      patient subsets is unexplained but raises the possibility that gB genotypes may
      serve as a marker for pathogenicity of CMV strains in marrow transplant patients.

PMID- 8133091
TI  - Increasing incidence of adenovirus disease in bone marrow transplant recipients.
AB  - Adenovirus infections in 201 bone marrow transplant (BMT) recipients over 4 years
      were retrospectively reviewed. Forty-two patients (20.9%) had positive adenovirus
      cultures after BMT. There was a higher incidence of adenovirus infections in
      pediatric patients than in adults (31.3% vs. 13.6%, P = .003). In addition, the
      time of onset of adenovirus infection after transplant was earlier in pediatric
      patients (mean, < 30 days) than in adults (> 90 days). Adenovirus type 35 was the
      most common serotype identified. One-third of adenovirus-positive patients had
      definite or probable adenovirus disease. Moderate to severe acute graft-versus
      host disease and isolation of adenovirus from two or more sites were significant
      risk factors for adenovirus disease. This report documents a higher incidence of
      both adenovirus infection and disease than do previous studies. Adenovirus may
      emerge as a more frequent pathogen as more high-risk BMT transplants are done.

PMID- 8133092
TI  - Herpes simplex encephalitis in the temporal cortex and limbic system after
      trigeminal nerve inoculation.
AB  - Herpes simplex virus type 1 causes an encephalitis in humans that is primarily
      restricted to the temporal lobe and limbic system. The distribution of lesions
      suggests that virus enters the brain from a single site and then spreads
      transneuronally to infect connected structures. Two obvious sites of potential
      viral entry are the olfactory and trigeminal nerves. Trigeminal nerve entry is
      more likely because it innervates the oral cavity, a common site of initial
      infection, and the trigeminal ganglion is the most common site of viral latency.
      In previous reports, however, experimental trigeminal nerve infection has never
      led to the pattern of disease observed in humans. By directly inoculating virus
      into the murine tooth pulp, the mandibular division of the trigeminal nerve was
      selectively infected. This division, which innervates the oral cavity, is the one
      most commonly infected in humans. Intrapulp inoculation led to an encephalitis
      primarily affecting the temporal cortex and limbic system. Thus, spread via the
      trigeminal nerve provides an explanation for the distribution of herpes simplex
      virus observed in the human encephalitis.

PMID- 8133093
TI  - Immunotherapy of acute and recurrent herpes simplex virus type 2 infection with
      an adjuvant-free form of recombinant glycoprotein D-interleukin-2 fusion protein.
AB  - Previous studies demonstrated that the adjuvant-free form of a fusion protein
      consisting of a truncated herpes simplex virus type 1 (HSV-1) glycoprotein D and
      human interleukin-2 (tgD-IL-2) elicited superior protective immunity in mice. In
      this study, the immunotherapeutic efficacy of tgD-IL-2 against vaginal HSV-2
      infection was investigated using a guinea pig model. Footpad injections of tgD-IL
      2 (12.5 micrograms/dose) after the onset of primary lesions strongly suppressed
      recurrence in the chronic phase of infection; consequently, the number of days
      with lesions was reduced 65%. Continuous medication with 100 mg/kg/day acyclovir
      for 5 days failed to suppress recurrent infection. In a UV radiation-induced
      recurrence model, prophylactic tgD-IL-2 significantly suppressed both duration
      and severity of disease. A single injection of tgD-IL-2 plus acyclovir produced
      an additive effect on the suppression of the disease in the acute phase. These
      results suggest that tgD-IL-2 is a promising immunotherapeutic agent against HSV
      2 genital infections.

PMID- 8133094
TI  - The prevalence of cervical infection with human papillomaviruses and cervical
      dysplasia in Alaska Native women.
AB  - Alaska Native women historically have high rates of sexually transmitted diseases
      (STDs) and invasive cervical cancer. Their prevalence of cervical infections with
      human papillomavirus (HPV) in relation to cervical dysplasia was determined with
      a commercial dot hybridization test for seven HPV genotypes. Type-specific HPV
      DNA, similarly distributed between genotype groups 16/18 and 31/33/35, was
      detected in 234 cervical specimens (21%) from 1126 Alaska Native women seeking
      routine care and colposcopy or from population-based lists. The prevalence of HPV
      DNA declined with age and increased with sexual activity and cigarette smoking.
      It was unrelated to use of oral contraceptives or condoms or to STDs. Relative
      risks associating HPV with increasing severe grades of cervical dysplasia
      increased markedly with HPV infection, up to 7.1 for high-risk genotypes 16/18
      and 14.4 for coinfection with 31/33/35. These genotypes were detected in 8% of
      women without dysplasia seeking routine care. Screening for strain-specific HPV
      DNA may identify women at highest risk for cervical neoplasia.

PMID- 8133095
TI  - Determination of hepatitis E virus seroprevalence by using recombinant fusion
      proteins and synthetic peptides.
AB  - Recombinant antigens from hepatitis E virus (HEV) open-reading frames 2 and 3
      were expressed in Escherichia coli as cytidine monophosphate-2-keto-3
      deoxyoctulosonic acid synthetase (CKS) fusion proteins, purified, and used to
      develop an EIA for the detection of antibodies. Serologic results were compared
      with those of previous assays by testing 102 samples from an HEV outbreak in
      Somalia. This CKS/HEV EIA detected anti-HEV in all 97 sera found reactive
      previously and in an additional 2 samples, which were shown to be true HEV
      positive samples by supplemental peptide and Western blot tests. The CKS/HEV EIA
      and supplemental assays were then used to determine seroprevalence of HEV
      worldwide. HEV seroprevalence ranged from 1% to 25%, with higher rates found in
      Middle Eastern countries. Also, 7%-14% of acute cases of non-A, -B, or -C
      hepatitis were HEV-positive. Thus, this CKS/HEV EIA appears useful for detecting
      anti-HEV in various populations.

PMID- 8133096
TI  - Intracerebral transmission of scrapie to cattle.
AB  - To determine if sheep scrapie agent(s) in the United States would induce a
      disease in cattle resembling bovine spongiform encephalopathy, 18 newborn calves
      were inoculated intracerebrally with a pooled suspension of brain from 9 sheep
      with scrapie. Half of the calves were euthanatized 1 year after inoculation. All
      calves kept longer than 1 year became severely lethargic and demonstrated
      clinical signs of motor neuron dysfunction that were manifest as progressive
      stiffness, posterior paresis, general weakness, and permanent recumbency. The
      incubation period was 14-18 months, and the clinical course was 1-5 months. The
      brain from each calf was examined for lesions and for protease-resistant prion
      protein. Lesions were subtle, but a disease-specific isoform of the prion protein
      was present in the brain of all calves. Neither signs nor lesions were
      characteristic of those for bovine spongiform encephalopathy.

PMID- 8133097
TI  - Investigation of the potential role of Enterococcus faecalis in the
      pathophysiology of experimental peritonitis.
AB  - Two nonfatal models of peritonitis differing by the duration and the severity of
      the disease were studied in rats by implantation of Escherichia coli and
      Bacteroides fragilis with or without increasing concentrations of Enterococcus
      faecalis. Results were evaluated at 3 or 6 days after inoculation. The highest
      enterococcal concentrations (10(9) cfu/mL) enhanced the severity of the
      infection, evident by increased emaciation, increased peritoneal counts of E.
      coli and B. fragilis, and increased frequency of E. coli and B. fragilis
      bacteremia compared with enterococcus-free animals. Six therapeutic regimens (low
      dose amoxicillin + low-dose gentamicin, high-dose amoxicillin + high-dose
      gentamicin, pefloxacin, ornidazole, pefloxacin + ornidazole, imipenem +
      gentamicin) were tested. All treatments failed to eradicate E. faecalis except
      the combination pefloxacin + ornidazole, which achieved a significant reduction
      of local bacterial counts and suppressed bacteremia. Enterococcus played an
      important role in the mechanisms of bacterial synergy in experimental
      peritonitis. However, eradication of enterococcus did not seem possible by
      conventional antienterococcal therapy.

PMID- 8133098
TI  - Internalization of Escherichia coli into human kidney epithelial cells:
      comparison of fecal and pyelonephritis-associated strains.
AB  - A gentamicin survival assay, using primary human renal epithelial cells and
      Escherichia coli strains isolated from the feces of asymptomatic individuals and
      from the urine or blood of patients with acute pyelonephritis, was used to
      investigate bacterial internalization as a model for renal parenchymal invasion
      in pyelonephritis. E. coli strains, regardless of their origin, efficiently
      entered into human renal epithelial cells, a process inhibited by cytochalasin D.
      While the percentage of survival of nonhemolytic pyelonephritis isolates did not
      differ from that of fecal isolates, survival of hemolytic pyelonephritis strains
      was lower than that of nonhemolytic strains, perhaps as a consequence of the
      greater cytotoxicity of hemolytic strains. There was no evidence of intracellular
      multiplication of E. coli. These results demonstrate that human renal epithelial
      cells are capable of efficient uptake of E. coli regardless of the source of the
      bacteria.

PMID- 8133099
TI  - Bacterial killing by neutrophils in hypertonic environments.
AB  - The effects of hypertonic sodium chloride and urea solutions on the phagocytosis
      and killing of Escherichia coli by neutrophils were examined. Neutrophil function
      was progressively inhibited by increasing osmolarity, with sodium chloride more
      inhibitory than urea. However, neutrophils killed at 25% of normal rates in 500
      mosmol/L NaCl, and in 300 mosmol/L NaCl with 800 mosmol/L urea. These
      concentrations would rarely be exceeded in the human urinary tract. Inhibition of
      neutrophil superoxide production and degranulation was similar to that observed
      with phagocytosis and killing. Neutrophils also phagocytosed and killed E. coli
      in isotonic and hypertonic urine, but no improvement in function attributable to
      the uptake of urinary osmoprotectants was evident. It is concluded that
      physiologic levels of sodium chloride and urea will slow, but not prevent,
      neutrophil activity at a hypertonic site of infection.

PMID- 8133100
TI  - Duration of antibody response after meningococcal polysaccharide vaccination in
      US Air Force personnel.
AB  - The long-term kinetics of the immunologic response after vaccination of adults
      with Neisseria meningitidis polysaccharide vaccine is unknown. Total
      meningococcal anti-capsular antibody response (measured by ELISA) and serum
      bactericidal activity after routine vaccination with quadrivalent meningococcal
      vaccine were evaluated in US Air Force personnel. In a retrospective cross
      sectional study, blood samples were obtained from approximately 40 personnel
      before vaccination, at 1 and 4-6 months, and at 2, 3, 4, 6, 8, and 10 years after
      vaccination. Total anti-group A and -group C capsular antibody levels and
      bactericidal activity peaked 1 month after vaccination and declined substantially
      by 2 years. At each interval, significantly higher levels of total antibody and
      bactericidal activity were detected than before vaccination. Anti-capsular
      antibodies and bactericidal activity persisted for up to 10 years after
      immunization. These and further studies on the serologic measure of protection
      against meningococcal disease are important for evaluation of candidate vaccines
      and development of recommendations for immunization.

PMID- 8133101
TI  - Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day
      regimen.
AB  - Four-day dexamethasone therapy has been used to treat bacterial meningitis. This
      prospective, randomized study compared the effect of a 2-day versus a 4-day
      regimen. Children (n = 118, ages 2.5 months to 15 years) were evaluated; 50% of
      the cases were due to Neisseria meningitidis and 40% to Haemophilus influenzae
      type b. Patients were treated intravenously (iv) mainly with conventional
      antimicrobial therapy and were randomly assigned to receive dexamethasone, 0.15
      mg/kg iv every 6 h for 2 or 4 days. The clinical response was similar for both
      dexamethasone regimens. The meningococcal meningitis patients survived without
      neurologic or audiologic sequelae. On long-term follow-up, neurologic sequelae or
      moderate or more severe unilateral or bilateral hearing impairment (or both) were
      found in 1.8% and 3.8% of patients treated with dexamethasone for 2 and 4 days,
      respectively. The 2-day regimen appears appropriate for the treatment of H.
      influenzae and meningococcal meningitis.

PMID- 8133102
TI  - Comparative pathogenesis of clinical and nonclinical isolates of Saccharomyces
      cerevisiae.
AB  - Although considered nonpathogenic, Saccharomyces cerevisiae is being encountered
      more frequently in the clinical setting. To assess pathogenic potential, 13
      clinical isolates, 10 nonclinical isolates, and 5 constructed strains of S.
      cerevisiae were analyzed. All were S. cerevisiae by biochemical profiles,
      sporulation, or genetic evidence. Intravenous inoculation of yeasts into CD-1
      mice showed that some clinical isolates proliferated in the brain (5-fold) but
      nonclinical isolates were cleared (1000-fold) by day 7 after infection.
      Comparison of burdens with those of YJM128 (clinical) and Y55 (laboratory strain)
      revealed three virulence groupings: virulent, those greater than or equal to
      YJM128 (5 clinical and 2 genetic constructs); intermediate virulent, those less
      than YJM128 and greater than Y55 (5 clinical, 3 genetic constructs, and 4
      nonclinical); and avirulent, those less than or equal to Y55 (1 clinical and 6
      nonclinical). Genetic crosses indicated that virulence was a dominant trait.
      Growth of various isolates at 37 degrees C and 39 degrees C indicated that
      temperature is associated with but not solely responsible for differences in
      virulence. These data demonstrate that some clinical isolates of S. cerevisiae
      can proliferate and resist clearance in vivo and support the potential of S.
      cerevisiae as a cause of clinical disease.

PMID- 8133103
TI  - Infection of human bone marrow stromal cells by hepatitis B virus: implications
      for viral persistence and the suppression of hematopoiesis.
AB  - Suspension cultures of bone marrow cells (BMC) were challenged with hepatitis B
      virus (HBV) to study interactions between the virus and the nonadherent and
      adherent BMC populations. Virus-challenged BMC developed an adherent stromal
      layer that differed in cellular composition from that of mock-infected cultures,
      showing a threefold increase in cells of the monocyte-macrophage lineage with an
      accompanying decrease in cells of the granulocytic lineage. Both viral envelope
      hepatitis B surface and core antigen expression was detected in adherent and
      nonadherent cell populations up to 10 days after virus challenge, which decreased
      thereafter. HBV DNA was still detectable in adherent cells 3 weeks after virus
      challenge, as shown by polymerase chain reaction analysis. These data indicate
      that HBV can infect not only bone marrow colony-forming cells but also the
      stromal cell populations involved with the regulation of hematopoiesis in vivo.
      Such virus-cell interactions could contribute to the immune dysfunction and bone
      marrow failure occasionally reported for patients with HBV infection as well as
      acting as an important site for HBV latency and persistence.

PMID- 8133104
TI  - Interferon (IFN)-alpha 2 genotype analysis of Chinese chronic hepatitis B
      patients undergoing recombinant IFN-alpha 2a therapy.
AB  - Sixteen Chinese chronic hepatitis B virus (HBV)-infected patients were treated
      with recombinant interferon-alpha 2a (rIFN-alpha 2a). Of these, 8 made a response
      to IFN, with titers of neutralizing antibody of 141-4525 as determined by an
      antiviral neutralization bioassay. To determine whether the immunogenicity of the
      IFN was directly linked to the patients' genotype, their genomic DNA was analyzed
      for the presence of the human IFN-alpha 2a gene. None of the patients possessed
      the gene for IFN-alpha 2a, but only 50% developed neutralizing antibodies. The
      hypothesis, therefore, of a direct link between antibody formation and genotype
      cannot be sustained. Alternative explanations of the immunogenicity of IFN-alpha
      2a must be sought.

PMID- 8133105
TI  - A rapid screen test for in vitro susceptibility of clinical herpes simplex virus
      isolates.
AB  - A rapid screening test for antiviral susceptibility to acyclovir and foscarnet
      was evaluated in 320 herpes simplex virus (HSV) isolates from 197 patients. Of
      the isolates tested (16% HSV-1, 84% HSV-2), 60% were resistant in vitro to
      acyclovir and 5% were resistant to foscarnet using the plaque reduction assay.
      The rapid screening test, requiring only 3 days to yield a preliminary
      susceptibility result, was highly associated with the results of the plaque
      reduction assay for acyclovir and foscarnet (P < or = .001 for each) and with the
      clinical response to antiviral therapy (P < .001, P = .001, respectively).

PMID- 8133106
TI  - Association of rotavirus and human immunodeficiency virus infection in children
      hospitalized with acute diarrhea, Lusaka, Zambia.
AB  - In Lusaka, Zambia, rotavirus (RV) and human immunodeficiency virus (HIV)
      infection commonly coexist; 132 (25%) of 537 consecutively studied infants < 5
      years old hospitalized with diarrhea were positive for both viral infections.
      Infants with RV infection were younger than those who were RV-negative (P > .05),
      and infants with both viruses more frequently experienced dehydration (P < .05).
      HIV-infected children more often exhibited respiratory symptoms on admission to
      the study (P < .0001) and were more frequently underweight (P < .0001) than were
      HIV-negative children, independent of RV infection. The mortality rate was
      highest in HIV-positive infants (P < .05), and coinfection with RV did not
      increase the risk of fatality. This study demonstrates that while RV and HIV
      infections commonly coexist in one region of Africa, RV infection is no more
      common nor is the illness more severe in HIV-positive infants.

PMID- 8133107
TI  - Protection against rotavirus disease after natural rotavirus infection. US
      Rotavirus Vaccine Efficacy Group.
AB  - Determination of protective efficacy after natural rotavirus infection is
      important as a basis for evaluating rotavirus vaccines. Therefore, placebo
      recipients in a large 2-year rotavirus vaccine trial conducted across the United
      States were followed to determine the protection afforded by natural rotavirus
      infection. Serotype 1 rotaviruses predominated (93% year 1, 66% year 2), but
      isolates of all four major human rotavirus serotypes circulated during both
      years. Of the 45 placebo recipients with documented rotavirus illnesses in year
      1, 1 developed rotavirus disease in year 2 compared with 29 of the other 235
      placebo recipients (P = .03). Serologic data were available for 171 placebo
      recipients, and 37 of 140 without rotavirus illnesses in year 1 had evidence of
      asymptomatic rotavirus infection. None of these 37 experienced rotavirus disease
      in year 2 compared with 22 of the remaining 103 (P < .001). Overall efficacy
      after natural rotavirus infection was 93% (95% confidence interval, 50%-99%).

PMID- 8133108
TI  - Enterovirus 71 infections and neurologic disease--United States, 1977-1991.
AB  - Since first described in 1974, enterovirus 71 infections have been associated
      with severe neurologic disease, and widespread infection was suspected in 1987.
      To investigate enterovirus 71 activity further, data were reviewed for isolations
      reported nationally during 1977-1991, virology laboratories were contacted
      regarding isolations during 1985-1989, and medical records were reviewed for
      respective patients, 1985-1989. From 1977 to 1991, 193 culture-confirmed
      enterovirus 71 infections were identified: > or = 1 isolate each year. In 1987,
      45 persons in 17 states were infected compared with a maximum of 22 persons in 1
      8 states in the other years. Of these 45, 27 (60%) had the following: paralysis
      (6), Guillain-Barre syndrome (1), meningitis (18), or encephalitis (2).
      Enterovirus 71 has been endemic in the United States since at least 1977, was
      identified more frequently in 1987 than in other years, and continues to be an
      occasional cause of severe neurologic disease.

PMID- 8133109
TI  - Epidemiology of pediatric meningitis caused by Haemophilus influenzae type b,
      Streptococcus pneumoniae, and Neisseria meningitidis in Israel: a 3-year
      nationwide prospective study. Israeli Pediatric Bacteremia and Meningitis Group.
AB  - In a 3-year nationwide prospective study on pediatric meningitis caused by
      Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria
      meningitidis in Israel, 1258 invasive infections with a known focus were
      observed. Meningitis was found in 482 (38%): 56%, 16%, and 76% of all infections
      by H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. The
      incidence of meningitis during the first year of life was 67.1, 17.5, and
      9.5/100,000 for H. influenzae type b, S. pneumoniae, and N. meningitidis,
      respectively, and in children < 5 years old it was 18.5, 5.3, and 5.2.
      Extrapolated for a population in which 100,000 live births occur yearly, 2097
      hospital days were required. The case fatality rate was 2.2%, 5.9%, and 6.3% for
      H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. Boys were
      affected significantly more often than girls, but mortality was higher among
      girls. On the basis of the observed serotypes and age distribution, even with
      optimal vaccine development in the next 5 years, it is not likely that > 50% of
      all cases will be prevented.

PMID- 8133110
TI  - Etiology of diarrhea in a rural community in western Thailand: importance of
      enteric viruses and enterovirulent Escherichia coli.
AB  - The etiology of gastroenteritis was determined in children and adults with
      diarrhea seen at a district hospital and three government health clinics in Suan
      Phung, western Thailand, in 1991. Enteric viruses (rotavirus and astrovirus) were
      identified in 40%, shigellae in 18%, attaching and effacing Escherichia coli in
      13%, Campylobacter jejuni in 9%, and enterotoxigenic E. coli in 7% of children <
      5 years old with diarrhea seen at the hospital. Enteric viruses were detected in
      15% (24/156) of patients with diarrhea > or = 5 years old and were the only
      enteric pathogens identified in 12 patients ages 7-79 years (2 astrovirus, 10
      rotavirus infections). Attaching and effacing E. coli, rotavirus, and astrovirus
      were potential causes of diarrhea in children and adults in this population.

PMID- 8133111
TI  - Controlled evaluation of copper-silver ionization in eradicating Legionella
      pneumophila from a hospital water distribution system.
AB  - A controlled evaluation was made of the efficacy of copper-silver ionization in
      eradicating Legionella pneumophila from a hospital water supply. Copper-silver
      ionization units were installed on the hot water recirculation line of one
      building with water fixtures positive for Legionella species. Another building
      with the same water supply served as a control. Legionella species persisted
      within the system when copper and silver concentrations were < 0.3 and < 0.03
      ppm, respectively. When copper and silver concentrations were > 0.4 and > 0.04
      ppm, respectively, there was a significant decrease in Legionella species
      colonization, but the percentage of water fixtures positive for organisms was
      unchanged in the control building. When the ionization unit was inactivated,
      water fixtures continued to be free of Legionella species for 2 additional
      months. Copper-silver ionization can eradicate L. pneumophila in a water
      distribution system. The advantages of copper-silver ionization include
      relatively low cost, straightforward installation, easy maintenance, nontoxic by
      products and the presence of a disinfecting residual.

PMID- 8133112
TI  - Diagnosis of babesiosis: evaluation of a serologic test for the detection of
      Babesia microti antibody.
AB  - To assess the possibility of standardization of a commonly used indirect
      immunofluorescent antibody (IFA) test for detection of Babesia microti antibody
      in human sera, the results from four reference laboratories were compared.
      Patients with babesiosis from southern New England (n = 25) and subjects with no
      history of babesiosis from southern New England (n = 55) and Iceland (n = 50)
      were enrolled in the study. Anti-Babesia antibody titers were determined in a
      blinded fashion by IFA test. The range of test results in the four laboratories
      was 88%-96% sensitivity, 90%-100% specificity, 69%-100% positive predictive
      value, and 96%-99% negative predictive value. Interlaboratory and intralaboratory
      concordance ranged from 84% to 85% and 94% to 100%, respectively. This B. microti
      IFA procedure is a sensitive, specific, and reproducible method for diagnosing
      babesiosis and is suitable for use as a standard in laboratories testing human
      sera for B. microti antibody.

PMID- 8133113
TI  - Salmonella typhi vaccine strain CVD 908 expressing the circumsporozoite protein
      of Plasmodium falciparum: strain construction and safety and immunogenicity in
      humans.
AB  - rcsp, encoding amino acids 21-398 of Plasmodium falciparum circumsporozoite
      protein (CSP), under control of tacP was integrated into the chromosomal delta
      aroC locus of attenuated delta aroC, delta aroD Salmonella typhi CVD 908. By
      immunoblot and ELISA, rCSP expression was greater from a multicopy plasmid than
      from the single chromosomal gene. CVD 908 omega (delta aroC1019::tacP-rcsp) was
      well tolerated by 10 volunteers who were fed two doses of 5 x 10(7) organisms 8
      days apart. Seven subjects excreted the vaccine strain for 1-3 days. All subjects
      developed serologic responses to O and H antigens of the live vector, whereas 3
      vaccinees responded to the foreign antigen: 1 developed an 80-fold rise in serum
      anti-sporozoite antibody, another had a 4-fold rise in antibody to a recombinant
      portion of CSP (residues 309-345), while a third vaccinee developed CSP-specific
      CD8+ cytotoxic T lymphocyte activity. This is the first report of attenuated S.
      typhi eliciting a human serologic or a cytotoxic T lymphocyte response to a
      foreign protein. Improved foreign gene expression should enhance immunogenicity.

PMID- 8133114
TI  - Blood stage antimalarial efficacy of primaquine in Plasmodium vivax malaria.
AB  - The blood stage antimalarial efficacy of primaquine (0.25 mg of base/kg of body
      weight/day over 14 days) and chloroquine (25 mg of base/kg over 3 days) were
      compared in 85 adult Thai men with acute Plasmodium vivax malaria. Most (75%) had
      at least one malaria episode previously. Parasite clearance times after
      primaquine alone (n = 30) were slower than after chloroquine (n = 30) or combined
      chloroquine-primaquine (n = 25), but all patients had a satisfactory initial
      therapeutic response. P. vivax malaria recurred in 10 (17%) of 60 patients
      followed for > or = 2 months and Plasmodium falciparum malaria developed in
      another 5 (8%) without reexposure to infection. Recurrences occurred < or = 5
      weeks after primaquine treatment (n = 4), suggesting recrudescence, whereas
      recurrences after chloroquine treatment (n = 6) occurred > or = 5 weeks later,
      suggesting relapse. Vivax malaria responds well initially to either primaquine or
      chloroquine. The blood stage antimalarial activity of primaquine may mask
      chloroquine resistance in combined regimens.

PMID- 8133115
TI  - Maternal cytomegalovirus infection and maternal age.

PMID- 8133116
TI  - Parvovirus B19 as a cause of anemia in human immunodeficiency virus-infected
      patients.

PMID- 8133117
TI  - Correlation between the progression of cervical dysplasia and the prevalence of
      human papillomavirus.

PMID- 8133118
TI  - Spastic paraparesis in a patient carrying defective human T cell leukemia virus
      type I (HTLV-I) provirus sequences but lacking a humoral or cytotoxic T cell
      response to HTLV-I.

PMID- 8133119
TI  - Human herpesvirus 6 infection in normal human brain tissue.

PMID- 8133120
TI  - Acute alterations of pre- and afterload: are Doppler-derived diastolic filling
      patterns able to differentiate the loading condition?
AB  - The net effects of acute changes in pre- and afterload on left ventricular
      filling, were examined by altering loading conditions in normal subjects. The
      specific purpose of this study was to investigate whether Doppler-derived
      transmitral flow patterns are able to differentiate the type of loading
      conditions. In 24 normal subjects (13 females, 11 males, mean age 44.1 +/- 11.5
      years), the following Doppler variables were determined at baseline, after rapid
      volume infusion (preload increase), after nitroglycerin administration (preload
      decrease), during isometric exercise (afterload increase), and after application
      of a converting enzyme inhibitor (afterload decrease): the peak and integrated
      early (E, Ei) and late (A, Ai) diastolic flow velocities, their ratios (E/A,
      Ei/Ai), the percentage of atrial contribution (ACON), and the acceleration and
      deceleration times (Ac, Dc) of early filling. Reduced preload and increased
      afterload led to similar filling patterns characterized by a significant E and Ei
      decrease (p < 0.05, compared to baseline) accompanied by an A and Ai increase
      with a resultant reduction of E/A and Ei/Ai. Both changes increased the atrial
      contribution to filling and reduced Ac and Dc. Increased preload only
      significantly increased E and Ei, while reduced afterload did not induce any
      significant changes. Different loading conditions alter Doppler-derived diastolic
      filling patterns. However, the transmitral flow profile is not specific enough to
      distinguish the manner in which loading conditions have been altered.

PMID- 8133121
TI  - Usefulness of echocardiography and Doppler in the detection of segmental
      myocardial ischemia.
AB  - Echocardiography and Doppler was performed in 20 patients during percutaneous
      transluminal coronary angioplasty of a right coronary artery to evaluate the
      usefulness of echocardiography and Doppler in the detection of segmental
      myocardial ischemia. Wall motion analysis was also compared to the occurrence of
      chest pain in relation to electrocardiographic and hemodynamic changes. Even in
      the case of small segmental myocardial ischemia, the two-dimensional
      echocardiographic evaluation of wall motion is superior to all other measured
      parameters. Contrary to this, the Doppler examination of transmitral flow is not
      sensitive enough in the detection of such small segmental myocardial ischemia,
      induced by right coronary artery occlusion.

PMID- 8133122
TI  - Intra- and interobserver variability of a fast on-line quantitative coronary
      angiographic system.
AB  - To evaluate intra- and interobserver variability of an on-line quantitative
      coronary angiographic system, 2 independent observers measured 166 primary
      lesions excluding total occlusions before and after coronary angioplasty. Each
      observer repeated his measurement 3 times at 14 days interval. The average
      percent diameter stenosis results obtained by observer 1 and 2 were almost
      identical, before (62.2% +/- 12.0% and 62.6% +/- 11.4%, NS) and after (27.1% +/-
      12.0% and 26.9% +/- 11.3%, NS) angioplasty. Variability was expressed as 95%
      limits of agreement (mean difference +/- 2 x SD). The intra-observer variability
      of observer 1 ranged from -6.6% to 6.6% before angioplasty and from -9.6% to 9.6%
      after angioplasty. The corresponding limits of observer 2 were -8.0% to 7.5% and 
      8.3% to 8.5%, respectively. The interobserver variability ranged from -10.4% to
      9.6% before versus -12.5% to 13.1% after angioplasty. This variability was not
      influenced by vessel size. The widening of the limits observed after angioplasty
      was largely due to an increased variability in the measurements of the absolute
      minimal luminal diameter but not of the reference segment. We conclude that the
      intra- and interobserver variability of measurements obtained with an on-line
      quantitative angiographic system used for guiding coronary interventions is
      acceptable and without systematic bias in any direction for a wide range of
      primary coronary stenoses. However, the variability increases when images are
      acquired immediately after angioplasty.

PMID- 8133123
TI  - Normal right ventricular systolic and diastolic function assessed by krypton-81m
      equilibrium ventriculography.
AB  - Krypton-81m equilibrium ventriculography was used to study right ventricular
      function in 23 healthy male volunteers. Technetium-99m lung perfusion
      scintigraphy was employed to subtract radionuclide activity within lung during
      image analysis thereby enhancing image quality. The imaging technique was used to
      generate a time-activity curve for the right ventricle allowing the definition of
      indices of normal systolic and diastolic function for the right ventricle. At
      rest, indices of systolic ejection and diastolic filling were comparable to those
      previously reported for the left ventricle. Using the imaging technique, movement
      artifact during exercise reduces image quality and limits accurate measurement of
      these indices to resting studies.

PMID- 8133124
TI  - The significance of transient left ventricular dilation during SPECT dipyridamole
      thallium-201 scintigraphy.
AB  - We assessed the significance of transient left ventricular dilation (TLVD) during
      single photon emission computed tomography (SPECT) dipyridamole thallium-201
      scintigraphy (DTS) in 49 patients who underwent both DTS and diagnostic coronary
      arteriography. Quantitative analysis of DTS images and independent review by 3
      experienced observers determined that 17 patients had TLVD and 32 patients had no
      TLVD. Patients with TLVD were similar to patients without TLVD with respect to
      age, history of myocardial infarction, coronary risk factors and occurrence of
      chest pain or electrocardiographic changes during DTS. The frequency of three
      vessel coronary artery disease (3VD) was greater in patients with TLVD than in
      patients without TLVD (94% vs. 16%, p < 0.01). The sensitivity of TLVD was 76%
      and the specificity 96% for the detection of 3VD. Of the 16 patients with 3VD who
      manifested TLVD, standard SPECT DTS analysis demonstrated defect or perfusion
      abnormalities in 14 patients and no abnormalities in 2 patients. In conclusion,
      the finding of TLVD during SPECT DTS is a specific marker for severe coronary
      disease and can provide additive information to standard SPECT thallium-201
      analysis.

PMID- 8133125
TI  - Uridine: a marker of myocardial viability after coronary occlusion and
      reperfusion.
AB  - Tissue accumulation of radiolabeled uridine, a precursor of uracil, reflects
      ribonucleic acid (RNA) synthesis and may be a marker of viability. To test this
      hypothesis, myocardial accumulation of H-3 uridine was compared to deoxyglucose
      uptake and histopathology in an experimental model of myocardial ischemia. In 18
      Wistar rats the left coronary artery was occluded for 5, 10 or 60 minutes
      followed by reperfusion. Five hours later H-3 uridine and C-14 deoxyglucose were
      administered intravenously and the animals were sacrificed 45 minutes later. The
      left ventricle of each animal was divided into 12 segments and myocardial tracer
      accumulation was determined by measurement of tissue radioactivity. From the
      results of TTC staining, the animals were divided into 3 groups: Group I-
      ischemia without infarction (n = 9); Group II--non-transmural infarction (n = 4)
      and transmural infarction (n = 5). Retention of uridine was observed in ischemic
      zones with enhanced deoxyglucose accumulation in Group I animals. Uridine
      accumulation was relatively preserved compared to slightly decreased deoxyglucose
      accumulation in regions of non-transmural infarction in Group II. In Group III,
      uridine accumulation decreased in parallel with deoxyglucose in zones of
      infarction. These result suggest that accumulation of radiolabeled uridine may be
      a useful indicator of viability in ischemic myocardium.

PMID- 8133126
TI  - Ambulatory ST-recording has no additional value to exercise test for
      identification of severe coronary lesions after an episode of unstable coronary
      artery disease in men.
AB  - One month after an episode of unstable coronary artery disease, 95 male patients
      performed coronary angiography, 48 hours ambulatory ST-recording and also an
      exercise test. ST-depression occurred in 29.5% during the ST-recording and in
      44.2% during the exercise test (p < 0.05). In patients with ST-depression at
      ambulatory monitoring, 79% demonstrated the same finding at the exercise test. A
      high risk response at the exercise test--defined as either ST-depression in > or
      = 3 leads, ST-depression in 1-2 leads with a maximal work load below the 60th
      percentile or a maximal work load below the 30th percentile regardless of the ECG
      reaction--occurred in 56.8%. Severe coronary lesions--defined as three vessel
      disease, left main stenosis or proximal left anterior descending artery stenosis
      as part of two vessel disease--was observed in 46.3%. Patients with a high risk
      exercise test response and patients with ST-depression during ST-recording had
      severe coronary lesions in 67% and 64% respectively. However, a high risk
      exercise test response occurred in 82%, while ST-depression at ambulatory
      monitoring was observed only in 41% of the patients with severe coronary lesions
      (p < 0.001). Thus, ambulatory ST-recording one month after an episode of unstable
      coronary artery disease in men adds no further information to a symptom limited
      exercise test in order to identify patients with severe coronary lesions.

PMID- 8133127
TI  - Long-term effect of inducible silent ischaemia on left ventricular systolic
      function.
AB  - Silent myocardial ischaemia is readily detected by exercise radionuclide
      ventriculography in patients with coronary artery disease. In those who remain
      asymptomatic and event-free, it is not known whether silent ischaemia which is
      inducible despite anti-ischaemic medication exerts an insidious detrimental
      effect on left ventricular function. To study this, 34 medically treated patients
      (mean age 57; 26 men) underwent prospective measurement of left ventricular
      ejection fraction (LVEF) during rest and exercise radionuclide ventriculography
      without interruption of anti-ischaemic medication at baseline and 12 months
      later. There was no significant mean (standard deviation, 95% confidence
      interval) deterioration from baseline to 12 months in LVEF at rest (50% v 49%, SD
      5; 95% CI = -3 to +1), peak exercise (44% v 45%, SD 8; 95% CI = -1 to +4) and the
      change in LVEF from rest to exercise (-6% v -4%, SD 7; 95% CI = -1 to +5). Thus,
      in coronary artery disease patients who remain asymptomatic and event-free on
      medical therapy, silent myocardial ischaemia which is readily inducible at
      baseline despite medication does not lead per se to deterioration of left
      ventricular systolic function at rest or exercise over 12 months.

PMID- 8133128
TI  - Single-day combined evaluation of regional myocardial perfusion and function at
      rest and peak exercise with 99mTc-MIBI in patients with coronary artery disease.
AB  - 99mTc-labeled methoxy-isobutyl-isonitrile (MIBI) allows a simultaneous
      radionuclide assessment of regional heart function and perfusion. In this study
      the effectiveness of functional and perfusional images obtained with 99mTc-MIBI
      in the detection of coronary stenoses was compared with that of their
      combination. We studied 197 patients who underwent coronary angiography and a
      single-day radionuclide protocol including first pass angiography (multicrystal
      gamma camera) and single photon emission computed tomography, by means of 2
      injections of 99mTc-MIBI at rest and at peak exercise. Fifteen patients had < 50%
      stenoses, 50 had 1-vessel, 69 2-vessel and 63 3-vessel disease, for a total of
      377 pathological major coronary vessels; 129 patients had previous myocardial
      infarction. Functional images, perfusional tomograms and their combination showed
      the same sensitivity (98%) and specificity (80%) in detecting coronary patients.
      Regional sensitivity and specificity of the combined analysis achieved 87% and
      82%, respectively, vs. 94% (p < 0.005) and 60% (p < 0.001) of functional images,
      and 88% (p = N.S.) and 74% (p < 0.05) of perfusional tomograms. Thus, the
      combined analysis of regional functional and perfusional abnormalities increased
      significantly the specificity in the detection of coronary stenoses, in
      comparison with the separate evaluation of function and perfusion, achieving also
      a slightly higher diagnostic accuracy (85%, vs. 81% and 83%, respectively). The
      results confirm that a single-day protocol simultaneously assessing regional
      myocardial function and perfusion with 99mTc-MIBI represents a rapid and
      effective diagnostic method, that allows the physician to assess the presence and
      functional importance of coronary stenoses in less than 4 hours.

PMID- 8133129
TI  - Transient periodicity and episodic predictability in biological dynamics.
AB  - Biological time series often contain passing episodes of nearly periodic
      dynamics. In chaotic systems, such transient periodicity can reflect the
      existence of semiperiodic saddles--nonstable invariant sets--contained in the
      attractor. Motion in the vicinity of such objects has a prominent periodic
      component. In addition, trajectories can become temporarily trapped in these
      neighbourhoods before exiting. The immediate dynamical antecedents (low-order
      preimages) of transient periodicity are well defined and, along with the saddles
      to which they map, correspond to regions of enhanced predictability under
      nonlinear forecasting. This suggests that it may be possible to forecast the
      onset of transient periodicity in systems for which overall predictability is
      low. The present paper reviews these concepts and applies them to biological
      phenomena at different levels of organization.

PMID- 8133130
TI  - A mathematical analysis of the Grodins model of respiratory control.
AB  - The classical Grodins model of chemical respiratory control is analysed. Scaling
      and asymptotic analysis are used to reduce the model drastically to a much
      simplified form. In essence, the model consists of two separate controllers due
      to oxygen and carbon dioxide. The authors focus on the carbon dioxide controller,
      and show that it can be considered as two coupled delay recruitment equations.
      While, in normal circumstances, steady ventilation is stable, it is shown that,
      by varying controlling parameters, periodic and chaotic solutions may be
      obtained.

PMID- 8133131
TI  - [Risks and benefits of gonadotrophin therapy for infertile patients with
      ovulatory cycles].
AB  - In an attempt to evaluate the risks and benefits of human menopausal
      gonadotrophin (hMG) therapy for patients with unexplained infertility, the
      response and outcome of hMG therapy for anovulatory patients and ovulatory
      patients with unexplained infertility were analyzed in a group of successful
      cases of pregnancy. The number of follicles grown and the total doses of hMG were
      not significantly different in the two groups. The rate of spontaneous abortion
      in unexplained cases was twice as high (13.2%) as in anovulatory cases. However,
      the rate of multiple pregnancy was 8.8% for unexplained cases which was
      significantly lower than that for anovulatory cases (39.0%). In addition, ovarian
      hyperstimulation syndrome (OHSS) occurred in 11.8% of unexplained cases and that
      was much lower than that for anovulatory cases (25.8%). This study justifies the
      application of gonadotrophin therapy to ovulatory patients with unexplained
      infertility in terms of the risks and benefits of the therapy in achieving
      pregnancy.

PMID- 8133132
TI  - [Effects of aromatase inhibitor on sexual differentiation of SDN-POA in rats].
AB  - The sexually dimorphic nucleus of the preoptic area (SDN-POA) of male rats is
      larger than that of females, the difference being caused by the perinatal effect
      of estrogen converted from androgen. To investigate the role of estrogen
      formation in the SDN-POA during the critical period of this sexual
      differentiation, CGS16949A (0.5 mg/kg, sc) was injected into the mothers in the
      late gestational age(F) or into neonates for 14 days from birth(N). Animals were
      sacrificed on the 20th. day of gestation and 7 days after birth, and fetal and
      neonatal brain aromatase activities (AA) as well as serum levels of
      testosterone(T) and corticosterone(B) were measured. On the 30th day after birth,
      the offspring of treated mothers and neonatally treated rats were sacrificed and
      the cross-sectional areas of the SDN-POA were evaluated by image processor NEXUS
      6800. In group F, CGS16949A markedly suppressed brain AA in vitro (fetal
      hypothalamus: IC50 1.4nM) and in vivo in both the hypothalamus and amygdala.
      However, the levels of T and B did not show any significant change in group F.
      The same depression of AA was also observed in group N on the 7th day after
      birth. In CGS-treated males in groups F and N, the SDN-POA area markedly
      decreased to that of control females. The area in males in group F was not
      significantly different from that in females. These results suggest that estrogen
      converted from androgen plays a dominant role in the development of sexual
      dimorphism of the SDN-POA, and that the brain AA in the pre- and postnatal period
      is important in this process.

PMID- 8133133
TI  - [Significance of the glucose concentration in amniotic fluid for the prediction
      of chorioamnionitis in preterm labor].
AB  - For the rapid and accurate prediction of the presence of chorioamnionitis (CAM)
      in preterm labor, amniotic fluid analyses were performed in 46 women with preterm
      labor between 24 to 34 weeks' pregnancy. Ultrasound-guided transabdominal
      amniocentesis was performed on admission and the amniotic fluid was subjected to
      the measurement of cell count, glucose, protein and chlorine concentration
      according to cerebrospinal fluid and neutrophil esterase analysis. The data
      demonstrated that the amniotic fluid glucose concentration was significantly
      lower in women with preterm birth/CAM(+) than that with preterm birth/CAM(-) and
      term birth (19.0 +/- 9.1, 28.0 +/- 7.6, 51.6 +/- 14.5 mg/dl, respectively). All
      of the women with a glucose concentration of 20mg/dl or less showed signs of CAM.
      By setting up a cut off value of 25mg/dl, both high sensitivity (81.8%) and
      specificity (91.4%) for the prediction of CAM were obtained. Positive predictive
      values for CAM of a glucose concentration of 20mg/dl or less and 25mg/dl or less
      were 100% and 75% respectively. It was concluded that amniotic fluid glucose
      concentration measurement is useful for the prediction of CAM. The presence of
      CAM should be considered when the amniotic fluid glucose concentration is 25mg/dl
      or less.

PMID- 8133134
TI  - [Influence of pregnancy on the vascular response to norepinephrine and serotonin
      in rat carotid artery].
AB  - Because the frequency of migrainous attacks tends to decrease in late pregnancy,
      we speculated that the responsiveness of the cerebral arteries to vasoactive
      amines which are associated with migraine changes during pregnancy. We therefore
      measured the effect of norepinephrine and serotonin on isometric contractions of
      the isolated carotid arterial rings in pregnant (n = 18) and nonpregnant rats (n
      = 18). The response of the arterial rings to norepinephrine was decreased
      significantly in the pregnant rat (p < 0.02) compared with the nonpregnant rat.
      This refractoriness to norepinephrine in the pregnant rat exists in both the
      following conditions: indomethacin (5 x 10(-7) mol/L), an inhibitor of production
      of prostaglandin, added to the reacting solution, and endothelium was removed.
      There was no difference in the maximal contraction tension in each condition. We
      did not observe any difference in the response to serotonin in the pregnant rat
      carotid artery compared with the nonpregnant one. In order to assess the activity
      of the endothelium-derived relaxing factor, we then measured the dilating
      response to acetylcholine in precontracted carotid arterial ring with 10(-7)
      mol/L norepinephrine. There was no difference in the dilating response. These
      finding indicated that the refractoriness of pregnant rat carotid artery to
      norepinephrine was not induced by endothelial factors, such as prostaglandin, or
      by an endothelium-derived relaxing factor.

PMID- 8133135
TI  - [Evaluation of the effects of vibro-acoustic stimulation test on the fetus during
      labor under epidural analgesia and evidence of its safety by way of auditory
      brainstem response].
AB  - This study was undertaken to elucidate the effects of epidural analgesia on vibro
      acoustic stimulation test (VAST) during normal labor and auditory brainstem
      response (ABR) in fifty full term parturients without any complication. The
      safety of VAST in relation to the ABR of neonates was also studied. The results
      were as follows, 1) There were some changes in CTG monitoring in five cases (10%)
      in the 10 minutes after epidural analgesia. However, these changes were not
      ominous signs but all related to the coiling of the cord, as previously reported.
      2) The ABR latency-intensity curve (audio-function of the newborn infants)
      revealed no hazardous change in VAST-loaded infants or in the controls. The
      response threshold was 10dB in this study. The application of VAST to the
      parturients under epidural analgesia was therefore not only harmless to the
      fetuses but also a useful way to evaluate fetal well-being.

PMID- 8133136
TI  - [Recurrent endometrial cancer after complete surgery].
AB  - Between 1974 and 1991, 576 patients with endometrial cancer were treated with
      complete surgery. 1. The overall relapse rate was 14.4%. No recurrence was
      observed in surgical stage Ia, whereas 56.8% relapse was noted in stage IIIc. 2.
      The relapse rate in cases with adenocarcinoma was 13.0%. The relapse rate
      increased with poorer differentiation. Five of 6 cases with serous adenocarcinoma
      developed recurrence. 3. Myometrial invasion, size of tumor, vessel permeation,
      cervical involvement, adnexal metastasis and lymph node metastasis were
      significant factors for relapse. 4. Distant recurrence was noted in 63.9% of
      recurrent cases and 28.9% developed pelvic recurrence. The most common recurrent
      sites were lung, peritoneal cavity, and para-aortic lymph node in distant relapse
      and vaginal vault and parametrium in pelvic relapse. 5. The time to relapse
      ranged between 106 days and 5,518 days after complete surgery. Thirty one point
      three % of the recurrent cases manifested relapse within the first year, 60.2%
      within 2 years and 93.9% within 5 years. The mean time to relapse was 561 days.
      It was concluded that adjuvant therapy for cases with adnexal metastasis, lymph
      node metastasis, cervical involvement, adenocarcinoma (G3), and serous
      adenocarcinoma should be established urgently.

PMID- 8133138
TI  - [Clinical significance of endocervical curettage (ECC) in predicting neoplastic
      lesions of the cervix].
AB  - Endocervical curettage (ECC) was routinely performed at the time of colposcopy on
      200 cases with an abnormal PAP smear. Colposcopically, 77 cases were normal, 99
      were abnormal, and 24 were unsatisfactory. Results of the directed biopsies were
      within normal limits for 84 cases, glandular dysplasia for 2, squamous dysplasia
      for 95, carcinoma in situ (CIS) for 17, and squamous cell carcinoma for 3.
      Histologic diagnoses of the ECC specimens were "tissue insufficient for
      diagnosis" for 11 cases, "benign endocervical tissue" for 167 including 9
      squamous metaplasias and 3 cervical polyps, "fragments of dysplasia" for 12, CIS
      for 6, and squamous carcinoma for 4. Regarding 73 cases who underwent surgical
      treatment, the biopsy diagnosis had been either false negative in 6 cases or
      underestimated in 5 cases as compared to the confirmed diagnosis. That is to say,
      11 cases might have been diagnosed incorrectly without ECC. The major lesion was
      located within the endocervix in most of such cases. It is therefore suggested
      that ECC improves the accuracy of the histologic diagnosis of premalignant and
      malignant lesions of the cervix and that ECC is an essential procedure especially
      in endocervical lesions.

PMID- 8133137
TI  - [Risk factors for retroperitoneal lymph node metastasis in ovarian cancer].
AB  - The incidence and significant risk factors for retroperitoneal lymph node
      metastasis were investigated in 48 patients with primary epithelial ovarian
      cancer. Twenty-four (50.0%) of the 48 patients had para-aortic and/or pelvic
      lymph node metastases. In retroperitoneal lymphadenectomy at primary
      cytoreductive surgery, all patients with lymph node metastases were found to have
      both para-aortic and pelvic lymph node metastases. It is possible that the
      lymphatic extension, from the pelvic lymph node to the para-aortic lymph node, is
      one of the routes of retroperitoneal lymph node metastases in primary epithelial
      ovarian cancer. The incidence of lymph node metastases significantly increased
      with the spread of the abdominal tumor, peritoneal cytology, peritoneal
      metastasis, omental metastasis, involvement of both ovaries and poor histological
      grade. In the multiple analysis, the spread of the abdominal tumor, positive
      peritoneal cytology and poor histological grade were found to be the most
      important risk factors for retroperitoneal lymph node metastasis in ovarian
      cancer.

PMID- 8133139
TI  - [A clinical study on memory function in climacteric and periclimacteric women].
AB  - This study was designed to investigate memory function in climacteric and
      periclimacteric women who lived a normal, ordinary life. Two hundred women
      treated at the gynecological outpatient clinic of Koshigaya Hospital were divided
      into 7 groups: groups A(31-35 yr), B(36-40 yr), C(41-45 yr), D(46-50 yr), E(51-55
      yr), F(56-60 yr) and G(61-65 yr). Each group consisted of 30 women except group
      G(n = 20). The memory function of each group was determined and the mean scores
      for 10 paired hard-associates after three trials of presentation were compared.
      The mean scores (+/- SD) for groups A and B were 8.0 +/- 2.0 and 8.2 +/- 1.7,
      respectively, which were not statistically different. The scores for both groups
      were significantly higher than those for the other groups (p < 0.01). The mean
      scores for groups C and D were 5.9 +/- 2.1 and 5.6 +/- 2.4, respectively, which
      were not statistically different. The score for group C was significantly higher
      than those for groups E(4.5 +/- 2.4), F(4.2 +/- 2.2), and G(3.3 +/- 1.6) (p <
      0.05). The score for group D was significantly higher than those for groups F and
      G(p < 0.05). The score for group E was significantly higher than that for group
      G(p < 0.01). The decrease in memory function was the greatest in group C. In the
      climacterium, memory impairment was also observed in group E. The former
      corresponds to the climacteric commencement age group where cyclic changes in
      serum estrogen levels decrease or cease, and the latter corresponds to the age
      group for menopause.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133140
TI  - [Two cases of retroperitoneal fibrosis diagnosed preoperatively as gynecological
      malignant tumors].

PMID- 8133141
TI  - [Effect of dietary supplementation with eicosapentaenoic acid on EPH gestosis].

PMID- 8133142
TI  - Persistent RNA virus infection and immunopathology.

PMID- 8133143
TI  - The ret/PTC oncogene in papillary thyroid carcinoma.

PMID- 8133144
TI  - G-protein regulation of insulin secretion.

PMID- 8133145
TI  - Duration of virus persistence and its relationship to inflammation in the chronic
      phase of coxsackievirus B1-induced murine polymyositis.
AB  - Mice infected with the Tucson strain of coxsackievirus B1 (CVB1T) develop chronic
      T cell-mediated polymyositis that is manifest as the acute infection resolves and
      is characterized by hindquarter weakness and muscle inflammation. This model
      system was used to study persistence of CVB1T RNA by using reverse transcriptase
      polymerase chain reaction (RT-PCR). For the most part, RNA persistence reflected
      the myotropic and neurotropic nature of the virus. At 1 month after infection,
      infectious virus was not detected in muscle, but persistent viral RNA was found
      in both skeletal and cardiac muscle, brain, and spinal cord. The kidney was
      weakly positive for viral RNA, whereas the liver and spleen were negative.
      Hindquarter muscle was assayed for persistent viral RNA at 1, 3, 6, 9, and 12
      months after infection. In a few cases, persistent viral RNA was detected as late
      as 12 months after infection. The incidence of persistent viral RNA was high at 1
      month after infection and gradually declined until, at 6 months and beyond, it
      was maintained in 3% to 12% of the muscles tested. Long-term viral RNA
      persistence was not more common in severely weak animals. However, the degree of
      hindquarter weakness that developed by 1 month was static thereafter and did not
      change over the 12-month study period. In contrast, separate experiments revealed
      that typical mononuclear cell (MNC) infiltration of muscle followed a time course
      similar to that of viral RNA persistence, peaking at 1 month and gradually
      resolving by 6 months. Infiltrating polymorphonuclear leukocytes (PMNs) and mast
      cells were present at 3 to 12 months after infection, signifying that some
      inflammatory activity remained. Other signs of myopathy that persisted for 12
      months included a lack of muscle regeneration, variations in fiber size, and
      myofiber atrophy with increased perimysial and endomysial connective tissue.
      These results demonstrate that coxsackievirus RNA can persist in muscle for
      extended periods of time and are compatible with the idea that persistent virus
      is involved in maintaining the chronic MNC inflammation observed in murine
      polymyositis.

PMID- 8133146
TI  - Alterations in human proximal tubule cell attachment in response to hypoxia: role
      of microfilaments.
AB  - Detachment of viable renal proximal tubular cells is seen in clinical and
      experimental acute tubular necrosis and may contribute to the acute renal
      dysfunction seen in acute tubular necrosis. Mechanisms of detachment of tubular
      cells are unknown but must involve changes in tubular cell adhesion. To begin to
      define mechanisms of altered cell adhesion, cultured human proximal tubular cells
      were made hypoxic by nitrogen gassing. Cells were monitored (blinded) for cell
      retraction and rounding over 90 minutes of N2. Hypoxia caused gradual alterations
      in cell shape, with 37.9% +/- 5.2% retracted-rounded cells by 90 minutes; control
      monolayers showed no significant change. Fluorescence confocal microscope imaging
      revealed that hypoxia caused displacement of actin filaments to basal margins of
      the retracted cells and produced a perinuclear aggregation of short filaments.
      Phalloidin (10(-6) mol/L), which stabilizes microfilaments and is able to
      penetrate these hypoxic cells, decreased the percentage of cells showing
      morphologic changes with hypoxia to < 5% by 90 minutes (p < 0.01). Viability, as
      assessed by Trypan blue dye exclusion, was well maintained (90% to 98% at 90
      minutes) and did not correlate with shape changes. In separate experiments,
      cytochalasin (10(-6) mol/L)--which depolymerizes microfilaments--but not
      nocodazole--which disrupts microtubules--produced cell shape change in non
      hypoxic monolayers. Disruption of microfilaments appears to play a role in loss
      of cell-to-cell and cell-to-substrate adhesion and loss of epithelial integrity
      in hypoxic injury to the renal tubule. These in vitro observations may be
      relevant to renal proximal tubular cell detachment in in vivo renal injury.

PMID- 8133148
TI  - Angiotensin-converting enzyme, bradykinin, and angiotensin II receptor binding in
      rat skin, tendon, and heart valves: an in vitro, quantitative autoradiographic
      study.
AB  - Angiotensin converting enzyme (ACE), an ectoenzyme bound to vascular endothelial
      cells, is also found at tissue sites (TACE) normally composed of fibrillar
      collagen and fibroblasts. For example, TACE is present in the adventitia of
      intramural coronary arteries and matrix of heart valves, as well as the fibrous
      tissue that follows the chronic administration of angiotensin II (AII) or
      aldosterone. At these sites bradykinin (BK) receptor but not AII receptor binding
      has been observed, suggesting that in fibrous tissue TACE uses BK as substrate.
      Dermis, subcutaneous tissue, and skeletal muscle tendon likewise are sites that
      are rich in fibrillar collagen but are different in their cellularity.
      Accordingly, we tested the hypothesis that TACE is normally present at sites of
      fibrous tissue and that BK--not AIK--receptor binding is anatomically coincident
      with TACE in keeping with its role as a kininase II. TACE and receptors for BK
      and AII were localized by quantitative in vitro autoradiography with [125I]351A,
      125I[Tyr8]BK, and 125I[Sar1, Ile8]AII, respectively. Skin morphology was examined
      in serial full thickness sections obtained from the dorsum of Sprague-Dawley
      rats. We found the following: (1) high TACE binding occurred in subcutaneous
      connective tissue and heart valves that was displaced by lisinopril or 351A in a
      dose-dependent manner; (2) BK receptor binding and low density AII receptor
      binding were seen at these sites, where AII receptor binding was totally
      displaced by a type 1 (DuP753) but not a type 2 (PD123177) receptor antagonist;
      (3) ACE, BK, and AII receptor binding was not evident in epidermis, dermis,
      skeletal muscle, or tendon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133147
TI  - Antibodies against biotinylated proteins are present in normal human serum.
AB  - Antibodies against biotinylated proteins have been identified in 10% of
      individuals tested (6/60). These antibodies bind readily to biotinylated proteins
      (50% inhibitory concentration = 0.59 mumol/L) but only modestly to free biotin or
      biocytin. It is unlikely that any clinical consequences occur as a result of
      these antibodies, because the affinity for free biotin is too low (50% inhibitory
      concentration = 0.51 mmol/L) to affect the normal level of free plasma biotin,
      0.5 nmol/L. The pathogenesis of this antibiotin immune response is unclear.
      Repeat testing of several individuals 5 months apart indicated that the
      antibiotin response was stable. In addition, 51 of the individuals tested for
      antibiotin antibodies were also examined for antiavidin antibodies. Whereas five
      were positive for antiavidin, only one individual was positive for both
      antibiotin and antiavidin antibodies. The presence of an antibiotin antibody is
      unlikely to affect the in vivo use of biotinylated proteins or cells in human
      subjects because its affinity for biotinylated proteins is modest and the level
      of biotinylation for in vivo studies is intentionally low. However, these
      antibodies may affect clinical or laboratory assays based on the biotin-avidin
      system where an antibiotin antibody may either positively or negatively affect
      the specific assay.

PMID- 8133149
TI  - Adoptive transfer of experimental hypersensitivity pneumonitis: CD4+ cells are
      memory and naive cells.
AB  - We previously demonstrated that CD4+ cells are responsible for transfer of
      adoptive murine experimental hypersensitivity pneumonitis. To further
      characterize the CD4+ cells as naive or memory cells, we depleted Micropolyspora
      faeni-sensitized cultured C3H/HeJ spleen cells of surface IgM+ cells by panning
      and Ia+ cells by lysis. We measured the proportion of CD4+ cells that expressed
      CD45RB, CD44 or LECAM-1 (markers used to distinguish memory from naive CD4+
      cells) in spleen cell populations able to transfer experimental hypersensitivity
      pneumonitis (M. faeni sensitized and cultured) and those unable to transfer
      experimental hypersensitivity pneumonitis (ovalbumin sensitized and M. faeni
      cultured). Planning reduced the proportion of B cells from 53% to 11% and of Ia+
      cells from 54% to 11%. Further lysis of Ia+ cells from the SIgM(+)-depleted
      population reduced Ia+ cells to 6%. Thy1+ cells increased from 26% to 55% after
      panning and to 72% after Ia+ cell lysis. Cultured M. faeni-sensitized spleen
      cells could transfer experimental hypersensitivity pneumonitis. Depletion of
      SIgM+ cells enhanced and depletion of Ia+ cells did not affect the capacity to
      transfer experimental hypersensitivity pneumonitis. The CD4+ cells from M. faeni
      sensitized animals were 47% CD45RBhi, 36% CD44+ and 0% LECAM-1hi before culture
      with M. faeni and 48% CD45RBhi. They were 34% CD44+ and 27% LECAM-1hi after
      culture. The origin of the cells (from M. faeni- or ovalbumin-sensitized animals)
      did not affect the phenotype of the CD4+ cells, either before or after culture
      with M. faeni. We conclude that the active cells in spleen cell cultures are SIgM
      , Ia-, CD4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133150
TI  - Reversal of desipramine toxicity in rats with polyclonal drug-specific antibody
      Fab fragments.
AB  - Drug-specific antibodies, or fragments containing their binding site(s), are a
      potential means of treating drug overdose. Affinity purified polyclonal ovine Fab
      (TFab) with a high average affinity constant (Ka = 1.4 x 10(10) M-1) for the
      common tricyclic antidepressants was evaluated as a possible treatment for
      tricyclic antidepressant toxicity. Groups of eight anesthetized rats received 30
      mg/kg body weight of desipramine (DMI) intraperitoneally, followed after 15
      minutes by a 10-minute intravenous injection of 3 ml normal saline solution, 2
      gm/kg nonspecific Fab as a control (CFab), or 1 or 2 gm/kg TFab (representing a
      molar ratio of TFab to DMI of 0.11 and 0.22, respectively). The animals were
      observed for 3 hours. During the initial 15 minutes, serum DMI levels in the four
      groups reached 2.3 to 2.9 micrograms/ml, the QRS duration increased by 67.5% to
      77.9%, and the systolic pressure fell to between 65% and 85% of its initial
      value. The group given saline solution showed a gradual return of all these
      parameters toward normal, whereas CFab caused a transient further QRS
      prolongation. CFab also caused an initial rise in blood pressure, which then fell
      progressively, and two of the rats died 2 to 3 hours later with hypotension and
      bradycardia. Serum DMI concentration did not change significantly in either the
      saline or CFab groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133151
TI  - Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF
      induced pulmonary edema.
AB  - We studied the role of reactive oxygen intermediates (ROI) in lipopolysaccharide
      (LPS)-induced pulmonary edema. LPS treatment (600 micrograms/mouse, IP) was
      associated with a marked induction of the superoxide-generating enzyme xanthine
      oxidase (XO) in serum and lung. Pretreatment with the antioxidant N
      acetylcysteine (NAC)--1 gm/kg orally, 45 minutes before LPS--or with the XO
      inhibitor allopurinol (AP)--50 mg/kg orally at -1 hour and +3 hours--was
      protective. On the other hand nonsteroidal antiinflammatory drugs (ibuprofen,
      indomethacin, and nordihydroguaiaretic acid) were ineffective. These data
      suggested that XO might be involved in the induction of pulmonary damage by LPS.
      However, treatment with the interferon inducer polyriboinosylic-polyribocytidylic
      acid, although inducing XO to the same extent as LPS, did not cause any pulmonary
      edema, indicating that XO is not sufficient for this toxicity of LPS. To define
      the possible role of cytokines, we studied the effect of direct administration of
      LPS (600 micrograms/mouse, IP), tumor necrosis factor (TNF, 2.5 or 50
      micrograms/mouse, IV), interleukin-1 (IL-1 beta, 2.5 micrograms/mouse, IV),
      interferon-gamma (IFN-gamma, 2.5 micrograms/mouse, IV), or their combination at
      2.5 micrograms each. In addition to LPS, only TNF at the highest dose induced
      pulmonary edema 24 hours later. LPS-induced pulmonary edema was partially
      inhibited by anti-IFN-gamma antibodies but not by anti-TNF antibodies, anti-IL-1
      beta antibodies, or IL-1 receptor antagonist (IL-1Ra).

PMID- 8133152
TI  - Acetylcholinesterase and butyrylcholinesterase activity in the human term
      placenta: implications for fetal cocaine exposure.
AB  - The characterization of the enzymes responsible for drug metabolism in the human
      placenta is of great importance in determining the possible role the placenta
      plays in protecting the fetus from potentially fetotoxic drugs. We speculate that
      the placenta metabolizes cocaine, serving to protect the fetus from the drug's
      ill effects. Cholinesterase, the principle enzyme that metabolizes cocaine, has
      been hypothesized to be present yet is not well characterized in the human
      placenta. The purpose of this study was to quantify human placental
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Human
      placentas were obtained from elective cesarean sections, and several lobules were
      thoroughly perfused with cold buffer to ensure minimal contamination from
      erythrocyte AChE. Subcellular fractions were then prepared from these lobules by
      using standard differential centrifugation techniques. Microsomes and cytosol
      were assayed for AChE and BChE activity by using a spectrophotometric assay. BChE
      activity was found in the cytosolic fraction of the placental villous tissue,
      whereas AChE activity was measured in the microsomal fraction. By demonstrating
      that BChE activity is present in human term placenta we have shown that this
      organ has the capacity to metabolize cocaine and may therefore serve as a
      metabolic barrier to fetal exposure to cocaine.

PMID- 8133153
TI  - Identification of the membrane remnants of transferrin receptor with domain
      specific antibodies.
AB  - Tissue culture studies with K562 and HL60 cells have demonstrated the production
      of a soluble form of transferrin receptor identical to that identified in human
      serum. The present study was undertaken to search for membrane remnants of the
      truncated receptor with peptide antibodies specific for the extracellular and
      cytoplasmic domain of transferrin receptor. In cell membranes, a 105K remnant was
      identified that is consistent with truncation of one extracellular domain monomer
      of the transferrin receptor. In the exosomal fraction of the culture supernatant,
      a smaller 20K remnant consistent with truncation of both extracellular domains
      was also demonstrated. These findings provide evidence that soluble receptor is
      the product of proteolytic cleavage of intact membrane-bound transferrin
      receptor. Prior studies showing that the concentration of the extracellular
      domain in exosomes remained stable during incubation in culture supernatant
      suggest that this cleavage possibly occurs intracellularly.

PMID- 8133154
TI  - The mechanism of thrombocytopenia in patients with HIV infection.
AB  - From a retrospective analysis of 85 patients with thrombocytopenia and HIV
      infection, in whom platelet production and destruction were studied by isotopic
      methods, the following conclusions are drawn. In most recently infected patients
      thrombocytopenia is due to accelerated platelet destruction; in these patients
      the platelet sequestration is predominantly splenic, and splenectomy is usually
      effective. The same pattern is seen in approximately one third of patients with
      more advanced disease (i.e., those with AIDS-related complex or frank AIDS). In
      most patients with AIDS-related complex or AIDS, the thrombocytopenia is due
      chiefly to a platelet production defect; splenectomy is less likely to help and
      is thus generally inadvisable. When the patients who were receiving zidovudine
      were examined separately, they were found to have a lesser rate of platelet
      destruction but also to have a more prominent defect in platelet production
      defect. This suggests that the drug may help blunt platelet destruction but may
      do so at a price in marrow response to the thrombocytolysis.

PMID- 8133155
TI  - Synthesis and transsulfuration of homocysteine in blood.
AB  - Interest in total plasma homocysteine (homocyst[e]ine) as a risk factor for
      atherosclerosis is expanding. However, the origin of plasma homocyst(e)ine has
      not been defined. Our studies examined the metabolism of homocyst(e)ine by blood
      cells as a potential contributor to the homeostasis of homocyst(e)inemia.
      Incubation of blood for 24 hours at 37 degrees C produced a threefold increase in
      the level of plasma homocyst(e)ine. In samples of fractionated blood cells
      incubated in vitro, increases in total plasma homocysteine were limited to
      incubated erythrocyte fractions and were influenced by addition of methionine.
      Anticoagulants had no significant effect. Incubation of blood in the presence of
      methionine tagged with sulfur 35 demonstrated incorporation of label into
      homocysteine and transsulfuration products. Similar incubations of blood cell
      fractions suggested that synthesis of homocysteine occurred in erythrocytes,
      whereas leukocytes both synthesized and transsulfurated homocysteine. These
      findings demonstrated a possible interaction of different blood cells in the
      metabolism of methionine, as well as their potential role as a source of total
      plasma homocysteine in plasma.

PMID- 8133156
TI  - Immunologic activation of hepatic macrophages in septic rats: a possible
      mechanism of sepsis-associated liver injury.
AB  - To investigate the pathogenesis of liver dysfunction accompanying intra-abdominal
      sepsis, we used rats with cecal ligation and punctures (CLP) and examined the
      expression of the inflammatory cytokines IL-1-alpha, IL-1-beta, and TNF-alpha, as
      well as the expression of a cell adhesion molecule, ICAM-1, in the liver. We also
      examined the expression of Ia antigen and interleukin-2 receptor (IL-2R) on
      hepatic macrophages. Hepatic macrophages isolated from rats 24 hours after CLP
      exhibited significantly higher IL-1 and TNF activity than those from control
      rats. Hepatic macrophages isolated from rats 72 hours after CLP exhibited the
      maximal IL-1 and TNF activity. In the hepatic nonparenchymal cells, IL-1-alpha
      mRNA was induced 1 hour after CLP, increasing to the maximal level 3 hours after
      CLP, whereas IL-1-beta mRNA was induced gradually, reaching a peak 6 hours after
      CLP. ICAM-1 mRNA reached a peak 3 hours after CLP. Induction of TNF-alpha mRNA
      was not detected by the present Northern blot analysis. Seventy-two hours after
      CLP, the proportions of hepatic macrophages expressing Ia antigens and IL-2R were
      increased significantly, as revealed by the flow cytometric analysis. In
      conclusion, the present study showed that hepatic macrophages are in an activated
      state in sepsis as indicated by their increased production of inflammatory
      monokines and their increased expression of immunomodulatory surface molecules.
      Further, we demonstrated the sequential induction of the mRNA of the various
      inflammatory cytokines and ICAM-1. These findings strengthen the notion that
      these cytokines are relevant to the pathogenesis of liver injury associated with
      sepsis.

PMID- 8133157
TI  - The deafness, pre-auricular sinus, external ear anomaly and commissural lip pits
      syndrome--otological, vestibular and radiological findings.
AB  - Commissural lip pits, pinna dysplasia, pre-auricular sinus and hearing loss
      constitute a recently described autosomal dominant branchial arch syndrome. In a
      large family, eight out of the 74 members were also affected by conductive
      hearing loss. No inner ear abnormalities could be demonstrated on the CT scans.
      In three patients (four ears) out of four patients (six ears), exploratory
      tympanotomy revealed serious ossicular chain anomalies. In one ear, round window
      aplasia was also present. Long-term hearing improvement could only be achieved in
      one ear.

PMID- 8133158
TI  - The use of the rigid endoscope in trans-sphenoidal pituitary surgery.
AB  - The use of the rigid endoscope has been evaluated during transsphenoidal
      microsurgery of 10 pituitary adenomas: three were prolactin-secreting adenomas;
      five growth hormone (GH)-secreting adenomas; and two without evidence of known
      endocrine activity. The use of the endoscope allowed close inspection and
      differentiation between tumour tissue and glandular remains. This resulted in
      microdissection of the tumour with maximum preservation of pituitary function.
      The angled view of the telescope helped total gross removal of tumour tissue from
      the less accessible supra- and para-sella extensions. More cases and a longer
      period of follow-up are necessary to provide long-term results.

PMID- 8133159
TI  - High-frequency jet ventilation--a review of its role in laryngology.
AB  - High-frequency jet ventilation (HFJV) is a safe, effective anaesthetic technique
      with a low risk of aspiration which has not yet gained wide acceptance in
      laryngology. Following anaesthesia and muscular relaxation the patient is
      intubated with a size 7FG infant feeding catheter and ventilation is achieved by
      delivering small bursts of anaesthetic gas at high frequency. The mechanisms of
      gas exchange are thought to be little different from those of conventional
      ventilation. We have found HFJV to be of value in laryngoscopy, laryngo-tracheal
      reconstruction, tracheoplasty, bronchoscopy and tonsillectomy. The advantages
      include: (a) ease of intubation, especially in the presence of a supraglottic
      mass; (b) improved surgical access compared with a conventional endotracheal
      tube; and (c) protection of the airway by the inherent 'auto-PEEP' effect. Care
      must be taken to ensure that conditions allow adequate exhaust of expired gas.
      Humidification of inspired gas is essential during prolonged procedures.

PMID- 8133161
TI  - Temporal bone dissection for display.
AB  - Increasing concern with medicolegal issues has heightened the need for surgical
      simulation in training. Familiarity with the surgical anatomy of the temporal
      bone is essential for effective and safe otological surgery. Refinement of
      surgical technique and intimate knowledge of temporal bone anatomy can be gained
      by accurate dissection. The products of such endeavours are both illustrative and
      instructive. The issues, methods and techniques necessary for display of
      anatomical dissections are discussed.

PMID- 8133160
TI  - Interjugular neck dissection and post-operative irradiation for neck control in
      advanced glottic cancers--are we justified?
AB  - At the Kidwai Memorial Institute of Oncology, advanced laryngeal cancers are
      subjected routinely to primary surgery and/or post-operative radiotherapy (RT).
      The surgery consists of wide field laryngectomy which entails total laryngectomy,
      ipsilateral/bilateral thyroid lobectomy, bilateral paratracheal clearance, and
      bilateral clearance of levels 2, 3 and 4 lymphatics. Post-operative RT is
      indicated in event of the following histopathological (HPE) situations to
      consolidate local-regional control: (1) T4 primary; (2) significant subglottic
      extension; and (3) jugular/paratracheal metastatic deposits. This prospective
      study highlights the therapeutic efficacy of this protocol at our centre in 45
      consecutive T4/T3 glottic cancers and specifically evaluates the role of
      interjugular dissection and/or post-operative RT in prevention of regional
      recurrence. Fifty-two per cent of primary lesions needed a post-surgical
      upstaging as against 14 per cent of the neck lesions. Accordingly 91 per cent of
      the cases (41/45) qualified for post-operative RT and 82 per cent (37/41)
      complied with the prescribed schedule. Recurrent disease in the lateral neck was
      noted in 2/37 who received the prescribed schedule and 1/4 non-compliant cases;
      while a recurrent central neck disease was noted in 1/37 and 1/4 of these cases
      respectively. All cases were followed-up for a period of two years and 66 per
      cent of the evaluable cases for a period of five years. This study confirms
      conclusively that our treatment schedule yields extremely gratifying two-year
      local-regional control rates of 89 per cent which translates into a two and five
      year actuarial survival rate of 92 and 70 per cent respectively.

PMID- 8133162
TI  - Temporomandibular joint capsule prolapse: a technique of repair using autograft
      cartilage.
AB  - Loss of bony integrity of the temporomandibular joint may result in prolapse of
      the joint capsule into the external auditory canal. This in turn gives rise to
      arthralgia, trismus and earache and a risk of septic arthritis. We describe a
      technique of repair which is simple, uses autologous tissue and has an acceptable
      cosmetic and functional result.

PMID- 8133163
TI  - Gastric tube transposition for cancer of the hypopharynx and cervical oesophagus.
AB  - A study of 20 cases of gastric tube transposition following total
      laryngopharyngoesophagectomy during an eight-year period is presented. The site
      of the tumour was: hypopharynx in 13 cases (12 pyriform sinus, 1 post-cricoid);
      and cervical oesophagus in seven cases. There were nine (45 per cent) Stage III
      lesions and 11 (55 per cent) Stage IV lesions (UICC, 1987). Post-operative
      morbidity rate was 15 per cent. Hospital mortality rate was 10 per cent (cause of
      death was myocardial infarction). Anastomotic fistula rate was five per cent.
      Excluding hospital mortality, the three year actuarial survival rate was 35 per
      cent for the whole series and 53 percent for patients with hypopharyngeal cancer.
      The actuarial survival rate for patients with oesophageal cancer at one and two
      years was 41 and zero per cent respectively. The transposition of a tubed stomach
      provided successful swallowing in two-thirds of the patients for a period of more
      than a year and these patients developed good neoesophageal speech.

PMID- 8133164
TI  - The influence of medical audit on the management of epistaxis in three district
      general Hospitals.
AB  - The implementation of audit in most hospital departments in the UK has been
      instigated by the guidelines set out by the Royal Colleges. This paper aims to
      demonstrate the results of regular subregional audit meetings in the ENT
      departments involving three District Hospitals in East Anglia. We report the
      effects of audit meetings in improving the management of epistaxis, whereby a
      protocol for treatment and discharge was established, the duration of the nasal
      pack left in situ was reduced, and the material of the pack was changed.

PMID- 8133165
TI  - Dilation of simultaneous laryngeal and oesophageal stricture with two T-tubes.
AB  - The treatment of double strictures in the airway and the oesophagus has always
      been time-consuming and causes additional suffering. A new technique using an
      open approach with the placement of two Montgomery silicone T-tubes to support
      and dilate the two strictures was successfully performed on a patient after
      caustic substance ingestion. Scar tissue was incised before two T-tubes were
      positioned into the larynx and oesophagus through a laryngo-fissure approach. The
      tubes remained in position for one year and no complications occurred. No foreign
      body sensation or prosthesis migration was observed and the patient had nearly
      normal peroral alimentation. After removal of the tubes, follow-up for an
      additional two years revealed no recurrence of the stenoses and normal
      alimentation without stridor. This technique permits simultaneous stenting of
      strictures of the larynx and oesophagus by using a connecting suture between the
      superior parts of two stents.

PMID- 8133166
TI  - The extraction and re-implantation of teeth for the difficult laryngoscopy.
AB  - We describe two cases where it was necessary to remove teeth to biopsy the larynx
      for malignant disease. Immediate reimplantation of the teeth proved successful.

PMID- 8133167
TI  - Use of the Carden anaesthetic tube for surgery around a tracheostome.
AB  - This short communication describes the use of the Carden anaesthetic tube during
      surgery in and around a tracheostome. The technique, which greatly facilitates
      access to the operating field, is described along with it's indications and
      contraindications. We would like to recommend extending the use of the Carden
      tube to operations around a tracheostome, thereby maximizing surgical access.

PMID- 8133168
TI  - Primary amyloidosis of the external auditory canal: case report.
AB  - A case of primary amyloidosis of the external auditory canal is described. To the
      best of our knowledge this is the first case described in the literature.

PMID- 8133169
TI  - Temporal bone fibrous dysplasia and cholesteatoma leading to the development of a
      parapharyngeal abscess.
AB  - Monostotic fibrous dysplasia of the temporal bone is a rare disease entity that
      may lead to progressive stenosis of the external auditory canal with resultant
      trapping of skin and the development of cholesteatoma. The cholesteatoma may
      extend widely into the temporal bone. Once cholesteatoma occupies the petrous
      apex, erosion out of the temporal bone can occur superiorly into the middle
      fossa, posteriorly into the posterior fossa, inferiorly into the neck, and infero
      medially into the parapharyngeal space. We present a case in which minimal
      symptoms were present despite a massive temporal bone fibrous dysplasia and
      cholesteatoma. Eventually, cholesteatoma eroded into the parapharyngeal space,
      leading to airway compromise. Late presentation occurred because the otic capsule
      was spared, there was no external skull deformity and there was slow inferior and
      medial growth that was well tolerated, until the development of a parapharyngeal
      space abscess.

PMID- 8133170
TI  - Acute bilateral vestibulo-cochlear dysfunction following occipital fracture.
AB  - The case of a 57-year-old man who presented with acute bilateral deafness and
      vestibular dysfunction following occipital bone fracture is described. Plain
      radiographs and a CT scan of the head demonstrated a single fracture of the
      occipital bone. Complete loss of cochlear and vestibular function bilaterally was
      demonstrated and followed by partial recovery of auditory function over the
      following months. Review of the literature has not revealed a previously reported
      case.

PMID- 8133171
TI  - Audiovestibular manifestations of the antiphospholipid syndrome.
AB  - We report on two patients who have high titres of antiphospholipid antibodies,
      both of whom had acute audiovestibular failure. One of the patients had systemic
      lupus erythematosus. The other patient had primary antiphospholipid syndrome:
      audiovestibular symptoms have not been reported in this condition. The occurrence
      of acute audiovestibular failure in the primary antiphospholipid syndrome raises
      the question as to whether patients presenting with acute deafness or vestibular
      disturbance should be screened for the presence of anticardiolipin antibodies.

PMID- 8133172
TI  - Spontaneous regression of a symptomatic laryngopyocoele.
AB  - A laryngopyocoele is a rarely encountered neck mass which may cause respiratory
      obstruction. Spontaneous regression of an established symptomatic laryngopyocoele
      is an even more unusual situation, since most of the reported cases require
      immediate intervention for impending airway obstruction. A case of a
      laryngopyocoele showing spontaneous regression after antibiotic therapy is
      presented and the clinical aspects are reviewed.

PMID- 8133173
TI  - An unusual cause of stridor in a neonate.
AB  - We report an unusual case of unilateral vocal fold palsy due to intracranial
      haemorrhage in a neonate with undiagnosed haemophilia A. Bleeding disorders in
      neonates are briefly discussed and the importance of a systemic investigation of
      stridor in children is emphasized.

PMID- 8133174
TI  - Uvulectomy to prevent throat infections.
AB  - It is common practice in many parts of Africa for traditional healers to remove
      the uvula to prevent infections and other disorders associated with the throat.
      We report two cases of children presenting with recurrent tonsillitis. On
      examination both children showed complete absence of the uvula and prominent
      tonsils. It was later revealed that they both had undergone uvulectomy, performed
      by traditional healers in Eritrea. We report this because this practice, although
      commonly performed, is little known to otolaryngologists practising outside
      Africa. In addition, although velopharyngeal competence seems to be maintained
      after uvulectomy, it may theoretically be at risk if adenoidectomy is performed
      in these patients.

PMID- 8133175
TI  - A common carotid artery aneurysm causing severe dysphagia.
AB  - Extracranial carotid artery aneurysms are rare, but are occasionally recognized
      as causing dysphagia. These aneurysms generally occur at or above the
      bifurcation. Here we present what we believe is a unique case: a common carotid
      artery aneurysm compressing the upper oesophagus, and mimicking the obstruction
      of a post-cricoid carcinoma.

PMID- 8133176
TI  - Bilateral pneumothorax after emergency tracheotomy: two case reports and a review
      of the literature.

PMID- 8133177
TI  - Evidence for thyroid development from the fourth branchial pouch.
AB  - Fourth branchial pouch anomalies are rarely reported. A case is described of an
      isolated branchial cyst which was found to contain ectopic thyroid tissue. This
      case, together with four others previously reported, support the theory that the
      thyroid gland may receive contributions from the fourth branchial pouch during
      development.

PMID- 8133178
TI  - Acquired involution of the maxillary antrum.
AB  - Maxillary sinus shrinkage can occur secondary to acquired benign osteomeatal
      disease. This may be associated with an external deformity and sinus wall
      sclerosis.

PMID- 8133179
TI  - True malignant mixed tumour of a minor salivary gland.
AB  - True malignant mixed tumours (carcinosarcomas) of salivary gland origin are rare
      and not widely recognized lesions. These tumours account for approximately 0.2
      per cent of all malignancies of the major salivary glands (Stephen et al., 1986).
      They usually occur in pre-existing pleomorphic adenomas of major salivary glands
      and have an aggressive and often rapidly fatal progression. We report a case of
      carcinosarcoma in a minor salivary gland of the upper lip. Its management and the
      use of immunocytochemical stains to demonstrate the separate epithelial and
      connective issue components are discussed.

PMID- 8133180
TI  - Adenocarcinoma arising in an oesophageal colonic interposition graft.
AB  - This case report describes the rare complication of an adenocarcinoma developing
      in a colonic interposition graft 20 years following surgical resection of a
      postcricoid squamous carcinoma. A free jejunal graft was used for further
      oesophageal reconstruction following resection of the colonic graft.

PMID- 8133181
TI  - Preparation of a temporal bone exhibit.
AB  - Temporal bone dissection forms an important aspect in the training of an
      otolaryngologist. The more dissection one does the more confident one is in the
      operating room. The aim of this paper is to advise in the preparation of temporal
      bones for the purpose of display, exhibition or competition. The practical
      aspects of dissection are deliberately avoided concentrating on the selection of
      bones pre- and post-dissection, preparation of the bones, fixing and display of
      vessels and nerves and also mounting and lighting for exhibition purposes. The
      temporal bone laboratory should be well equipped with a microscope, a power drill
      with a range of cutting and polishing burrs, a range of fine instruments, a
      suction machine with different sizes of suction tips, water source, a place to
      store the bones etc., thus creating an ideal environment for temporal bone
      dissection.

PMID- 8133182
TI  - Historical roots of the field of learning disabilities: some nineteenth-century
      German contributions.
AB  - The field of learning disabilities is often thought of as having come into being
      in the early 1960s. In reality, there is a long history of scientific
      investigation into psycho-anatomic functions. This article highlights the
      scientific contributions of some major nineteenth-century German researchers,
      their astounding attempts at describing neuropsychologic dysfunction, and their
      struggle to conceptionalize and cerebrally localize the clinical syndromes they
      had observed. After Pierre Paul Broca's discovery of "motor aphasia," Carl
      Wernicke described the clinical syndrome of "sensory aphasia" and its cerebral
      localization in 1871. Wernicke's investigation was at the onset of rapidly
      accumulating insights into the complexities of neuropsychologic functions as they
      were investigated by researchers such as Ludwig Lichtheim, Hugo Karl Liepmann, B.
      Berlin, Hubert Grashey, and J. K. Goldscheider. The long-term influence of this
      research on the development of the field of learning disabilities is discussed.

PMID- 8133183
TI  - Note-taking skills of university students with and without learning disabilities.
AB  - The notes of 30 university students with learning disabilities (LD) and 30
      nondisabled university students were compared on the number of cued and noncued
      information units recorded and the number and type of abbreviations used. Results
      showed that the university students with LD performed significantly lower on all
      variables. Implications for practitioners are provided and future research
      discussed.

PMID- 8133184
TI  - A decade of research on learning disabilities: a report card on the state of the
      literature.
AB  - A review of 208 studies of children with learning disabilities (LD) published in
      10 major journals between 1988 and 1990 was conducted to determine the extent to
      which recommendations made in 1980 and 1984 regarding reporting and design of LD
      research have been followed. A number of problems continue to threaten the
      interpretability and utility of results, including imprecise subject
      descriptions, heterogeneous samples, and methodological weaknesses. Implications
      for the field are discussed and recommendations for improvement are provided.

PMID- 8133185
TI  - Short-term memory and working memory: do both contribute to our understanding of
      academic achievement in children and adults with learning disabilities?
AB  - Seventy-five children and adults with learning disabilities (age range = 5.0 to
      42.10 yrs.) and 86 normally achieving children and adults (age range = 5.11 to
      58.0 yrs.) were compared on short-term memory (STM) and working memory (WM) tasks
      to assess the relationship between STM and WM, and to test whether these measures
      independently relate to achievement. For both ability groups, the factor analyses
      indicated that STM and WM loaded on different factors, and the regressions and
      partial correlations showed that these different factors accounted for separate
      variance in reading comprehension and mathematics. Both STM and WM are important
      in understanding reading comprehension and mathematics performance in children
      and adults with learning disabilities; however, WM is more important for children
      and adults without learning disabilities. In contrast to WM, STM contributed
      minimal variance to word recognition in both ability groups. Overall, it was
      concluded that STM and WM do reflect different processes, both of which seem to
      separate the two ability groups. However, models of memory that view STM and WM
      as interchangeable, or STM in isolation, do not provide an adequate framework for
      capturing academic performance in children and adults with learning disabilities.

PMID- 8133186
TI  - Resolution on adult education for persons with learning disabilities. Learning
      Disabilities Association of America.

PMID- 8133187
TI  - Preparing high school students with learning disabilities for the transition to
      postsecondary education: teaching the skills of self-determination.
AB  - Increasing numbers of students with learning disabilities (LD) are looking to
      postsecondary education and training to help them achieve success in career
      development and eventual job placement. Unfortunately, research suggests that
      many of these students are having difficulty staying in and completing
      postsecondary programs. A number of self-determination skills have been
      identified that are related to students' making a successful transition to
      postsecondary education. These include stating one's disability and its impact on
      school performance, and identifying instructional accommodations and strategies
      for arranging those accommodations with their regular classroom teachers. The
      purpose of this study was to examine whether these self-determination skills
      could be acquired through direct instruction, and subsequently generalized to
      general education classrooms. The results of the effectiveness of this self
      determination training are reported and their implications for teachers, parents,
      and students discussed.

PMID- 8133188
TI  - Researching adults with learning disabilities from an adult-development
      perspective.
AB  - As the field of learning disabilities begins to discover the manifold issues of
      adulthood, there is a need for a framework for studying adults with learning
      disabilities. Currently, the research on adults focuses primarily on service
      delivery systems. If a life-span developmental perspective is utilized as a
      conceptual approach in future research, then the knowledge gained will be more
      meaningful. Considerations for incorporating such essential concepts as mediating
      variables, context, and age-span phases into research on adults with learning
      disabilities are discussed.

PMID- 8133189
TI  - Screening for learning disabilities with teacher rating scales.
AB  - The purpose of the study was to investigate the use of teacher assessments in
      screening for learning disabilities. In a longitudinal study, 603 children were
      rated by their teachers in the second grade (age 8 to 9 years), and the ratings
      were correlated with examinations of reading, spelling, and intelligence in the
      third grade. The third-grade tests for reading, spelling, and intelligence
      classified children into groups with low achievement and dyslexia, and these two
      groups were compared with normally achieving children. The accuracy of teacher
      assessments, measured with correlation analysis, ROC curves, and kappa indices,
      showed that teachers were quite accurate in their judgment of low achievement,
      but somewhat less efficient in their judgment of specific reading difficulties.

PMID- 8133190
TI  - An eye-movement analysis of the effects of scotopic sensitivity correction on
      parsing and comprehension.
AB  - Does scotopic sensitivity correction enhance parsing and, thus, comprehension?
      Twenty-two readers with scotopic sensitivity (mean age = 20.3 yrs.; 40.9% male)
      parsed sentences under scotopic correction and control conditions. Measures
      included eye-movement indices of parsing and comprehension questions. Although
      eye movements suggested enhanced parsing, comprehension scores were not
      significantly improved with correction.

PMID- 8133191
TI  - Biomechanical characterization (fingerprinting) of five novel methods of cervical
      spine manipulation.
AB  - OBJECTIVE: To determine the biomechanical characteristics of five clinically
      common methods of cervical spine manipulation. DESIGN: Descriptive study.
      SETTING: Human Performance Lab, University of Calgary. PARTICIPANTS: Five
      volunteer practitioners treating symptomatic patients from their own clinical
      populations. INTERVENTION: Five commonly used methods of cervical spine
      manipulation: lateral break (LAT), Gonstead (GON), Activator (ACT), toggle (TOG),
      rotation (ROT). MAIN OUTCOME MEASURE: Mean thrust duration (msec), normalized
      mean peak force (N), slope (N/msec), force profile (graphic representation of the
      above values. RESULTS: Outcome measures for each manipulative technique were as
      follows: LAT = normalized mean peak force of 102.2 N at 86.7 msec, GON = 109.8 N
      at 91.9 msec, ACT = 40.9 N at 31.8 msec, TOG = 117.6 N at 47.5 msec, ROT = 40.5 N
      at 79.1 msec. CONCLUSION: The observed differences and similarities in force
      profiles between the five techniques studied here may partly be the manifestation
      of how a particular technique delivers force to the cervical spine. The clinical
      significance of force profile characterization is not yet known.

PMID- 8133192
TI  - Choice of controls in case-control studies.
AB  - This paper will explore the concepts of the choice of controls in observational
      analytic epidemiological case-control studies. An overview of the objects and
      basic concepts of case-control methodology along with a brief review of its
      historical development are presented. The definition and purpose of the control
      group are reviewed. The control's opportunity of exposure to the study variables
      is examined. Major sources of bias are reviewed and some solutions, emphasizing
      the control, are offered. Examples of case-control studies from
      neuromusculoskeletal literature are evaluated.

PMID- 8133193
TI  - Palpation--problems and implications.
AB  - Palpation is one of the main tools in manipulative therapy as well as diagnosis.
      Analysis of palpation shows that it combines two types of sensation: that of
      touch and of motion, i.e., proprioception. In addition, it causes interaction
      with the patient resulting in a feedback-situation, which further complicates
      reproduction, e.g., objectification and measurement. The objection to palpation
      being "subjective" is further enhanced by the discovery of palpatory illusion.
      Thus, there is an urgent need for research in palpation, which could provide
      basic scientific credibility to manipulative techniques.

PMID- 8133194
TI  - The curve of the cervical spine: variations and significance.
AB  - OBJECTIVE: To review the literature regarding the curve of the cervical spine in
      normal and injured persons, emphasizing common variations in cervical curvature
      and their possible clinical significance. DATA SOURCE: A MEDLINE literature
      search of the English-language, human literature was performed using multiple
      search strategies relevant to radiography, posture, lordosis, injury, diagnosis
      and prognosis of the cervical spine (MESH: cervical vertebrae). Additionally,
      article bibliographies were searched for further relevant articles. No
      publication time limit was imposed. STUDY SELECTION: Articles were identified by
      the author as being directly relevant to the objective and scope of this review.
      DATA EXTRACTION: Data was extracted as presented in each original article. DATA
      SYNTHESIS: The articles reviewed indicate that a wide range of normal exists in
      the posture and configuration of the cervical spine. Although kyphotic angulation
      and straightening or reversal of cervical lordosis are commonly seen following
      trauma, they may be normal variants. Muscle spasm is a widely used explanation
      for these variations when seen in patients with pain or trauma. Kyphotic
      angulation is often associated with posterior ligamentous injury of a motion
      segment. Prognostic significance of these variations is claimed by some authors.
      CONCLUSION: There is little evidence to support the contention that altered
      cervical curvatures are of prognostic significance. Although kyphotic angulation
      is associated with anterior subluxation (hyperflexion sprain), it is not a
      reliable diagnostic criterion for that condition. It is reasonable to assume that
      straightening or reversal of a previously lordotic cervical curve is the result
      of muscular spasm, but more specific interpretation is not supported by the
      literature. More study is needed to characterize the specific dynamics and
      etiologies involved in the determination of cervical spine configuration.

PMID- 8133195
TI  - Clinical presentation of a patient with multiple sclerosis and response to manual
      chiropractic adjustive therapies.
AB  - OBJECTIVE: To present a clinical case presentation of a patient with multiple
      sclerosis (MS). Diagnostic criteria are presented, including advanced imaging;
      and, for the first time, a potential relationship between chiropractic manual
      adjustive therapies and the symptoms associated with MS is presented. CLINICAL
      FEATURES: A 32-yr-old male presented with numbness from the lower trunk to the
      distal lower extremities, anteriorly and posteriorly, bilaterally equal. There
      was a family history suggestive of MS, reflexes were hyperactive, and
      hypoesthesia was present with the neurological pinwheel exam. There was evidence
      to suggest biomechanical vertebral segmental dysfunction. A second-opinion
      medical neurological evaluation and multifocal demyelination lesions confirmed
      with magnetic resonance imaging reinforced the working impression. Laboratory
      screening was conducted but was non-revealing. INTERVENTION AND OUTCOME:
      Conservative chiropractic manual adjustive therapies were provided to address
      spinal segmental dysfunction and the patient reported complete absence of
      symptoms following the first treatment intervention. It was at this time, in
      order to rule out other possibilities and to confirm the working impression of
      MS, that a second opinion with a medical neurologist was recommended. CONCLUSION:
      Manual adjustive therapies appear to be responsible for the dramatic symptomatic
      relief provided for a patient diagnosed with MS. The relative risk-to-benefit
      ratio suggests that this approach may be appropriate as an alternative symptom
      management approach for MS patients, and future research efforts can and should
      direct the comprehensive management approach to the treatment of this disorder.

PMID- 8133196
TI  - Destructive arthritis of the hip in a patient with Crohn's disease.
AB  - OBJECTIVE: Isolated destructive peripheral arthropathy is a rare complication of
      Crohn's disease. We describe the clinical course and radiographic findings of
      such a case. CLINICAL FEATURES: A 28-yr-old male presented to our chiropractic
      clinic with chronic left hip pain. The patient was known to have Crohn's disease.
      Five years earlier the gastrointestinal symptoms resolved with a brief course of
      prednisone. However, the left hip pain continued. A radiograph of the left hip
      was read as normal. Repeat radiograph, 2 yr later, revealed destructive changes
      of the left hip and, in retrospect, early destructive changes could be seen on
      the initial radiograph. INTERVENTION AND OUTCOME: The diagnosis, in this case,
      was destructive arthritis of the left hip secondary to Crohn's disease. The
      treatment selected in this case was observation and nonsteroidal anti
      inflammatory drug use. CONCLUSION: This diagnosis, a relatively rare complication
      of Crohn's disease, should be considered in a young adult patient with Crohn's
      disease and persistent peripheral joint pain.

PMID- 8133197
TI  - Myositis ossificans traumatica.
AB  - OBJECTIVE: To present a case of myositis ossificans traumatica (MOT) in a hockey
      player. Serial X-ray studies allow the reader an opportunity to observe MOT in
      its earliest through fulminated stages. CLINICAL FEATURES: A 20-yr-old hockey
      player was subjected to an acute blow to the lateral thigh. Copious amounts of
      swelling soon developed. The patient was unable to skate. X-rays were initially
      performed 4 hr after the injury and demonstrated a hugh mass developing in the
      thigh at that time. INTERVENTION AND OUTCOME: The player was inappropriately
      treated with deep tissue massage and heat at the time of injury. It is believed
      that this led to the fulmination and advanced degree of MOT development.
      Immobilization allowed for resorption of the calcific density of the ossified
      structure. CONCLUSION: Proper care of acute trauma is essential in disorders of
      this nature. Ice, immobility and recognition of when a possible MOT lesion is
      developing is essential when dealing with contact sports.

PMID- 8133198
TI  - A comparison of health care costs for chiropractic and medical patients.

PMID- 8133199
TI  - Five steps to your own technique: the Nelson method.

PMID- 8133200
TI  - Responsiveness of leg alignment changes associated with articular pressure
      testing to spinal manipulation: the use of a randomized clinical trial design to
      evaluate a diagnostic test with a dichotomous outcome.

PMID- 8133201
TI  - A comparison of outcome measures for use with back pain patients results of a
      feasibility study.

PMID- 8133202
TI  - Distraction manipulation reduction of an L5-S1 disk herniation.

PMID- 8133203
TI  - Effects of Asn87 and Asp318 mutations on ligand binding and signal transduction
      in the rat GnRH receptor.
AB  - The gonadotrophin-releasing hormone (GnRH) receptor is unlike other G-protein
      coupled receptors in that the highly conserved amino acids, Asp in the second
      transmembrane region and Asn in the seventh, are interchanged. Site-directed
      mutagenesis studies mutated these residues back to their normally conserved
      positions. Two single mutants Asn87Asp & Asp318Asn and one double mutant Asn87Asp
      Asp318Asn were transiently expressed in COS-1 cells and their effect on binding
      to GnRH and inositol phosphate production measured. The single mutant Asp318Asn
      had no effect on ligand binding but abolished GnRH-dependent inositol phosphate
      production, whereas mutations Asn87Asp and Asn87Asp Asp318Asn show a complete
      loss of GnRH binding and subsequent inactivation of its second messenger system.

PMID- 8133204
TI  - Growth hormone and its receptor: from structure to function.

PMID- 8133205
TI  - Parathyroid hormone: neural and neuroendocrine perspectives.

PMID- 8133206
TI  - Prolactin receptor expression in the gastrointestinal tract: characterization of
      the prolactin receptor of gastric mucosa.
AB  - There is evidence that prolactin (PRL) influences gastrointestinal function.
      However, the sites at which prolactin exerts these effects are not known. A
      monoclonal antibody was therefore generated against the rabbit mammary gland
      prolactin receptor (MAb 218) and used to study the distribution of the prolactin
      receptor in the rabbit gastrointestinal tract (GIT) by immunohistochemistry. MAb
      218 is an IgG1 kappa-precipitating antibody which precipitates major affinity
      cross-linked mammary gland prolactin receptor subunits of molecular masses 45 and
      80 kDa. It has an affinity of 0.8 x 10(9) mol/l for the prolactin receptor and
      does not react with GH or insulin receptors in precipitation assays. MAb 218
      immunoreactivity was observed in classical prolactin target cells such as mammary
      gland epithelium, and this immunoreactivity was abolished by preincubation of MAb
      218 with purified prolactin receptor but not by preincubation with purified GH
      receptor. In the GIT, the most intense immunoreactivity was associated with the
      oesophageal epithelium, chief (zymogenic) cells of the fundic mucosa, pancreatic
      islets of Langerhans and surface epithelial cells of the duodenum and jejunum.
      Other specific elements of the GIT were immunoreactive at lower levels or were
      immunonegative. No immunoreactivity was observed in these locations with a
      control monoclonal antibody (MAb 50.8) of identical isotype to 218. To support
      the immunohistochemical findings, rabbit gastric mucosal membranes were used to
      show the presence of lactogen-specific binding. Scatchard analysis of 125I
      labelled human GH binding to the gastric mucosal membranes with rat prolactin as
      displacing ligand yielded an affinity constant (Ka) of 1.0 +/- 0.2 x 10(9) mol/l
      with a capacity of 3.5 +/- 0.4 fmol/mg protein. Affinity cross-linking and sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis of the gastric receptor
      revealed lactogenic hormone-binding subunits of molecular masses 43, 68 and 83
      kDa. The 68 kDa subunit was not seen in rabbit mammary gland or ovarian tissue,
      and may be unique to gastric mucosa. In conclusion, we have demonstrated the
      presence of a high affinity lactogenic receptor in specific epithelial cell
      subpopulations of the GIT. This localization of the prolactin receptor in the GIT
      will assist in further functional assignment of prolactin to gastrointestinal
      physiology.

PMID- 8133207
TI  - Monoclonal antibodies to bovine growth hormone potentiate hormonal activity in
      vivo by enhancing growth hormone binding to hepatic somatogenic receptors.
AB  - Administration of GH complexed with monoclonal antibodies (MABs) potentiates the
      in vivo actions of the hormone. In particular, growth and serum IGF-I
      concentrations of GH-treated hypophysectomized rats are increased by concomitant
      injection of anti-GH MABs. Among 37 anti-bovine GH (bGH) MABs, we selected one
      MAB with the most potentiating effects to investigate the mechanisms responsible
      for this phenomenon. Hypophysectomized rats were killed 18 h after a single s.c.
      injection of bGH (100 micrograms/rat), alone or complexed with increasing doses
      of MAB (4, 40, 400 micrograms/rat; MAB:bGH molar ratio: 0.005, 0.05, 0.5). IGF-I
      was measured by radioimmunoassay in acid-extracted sera and livers, whereas liver
      IGF-I mRNA was quantified by Northern blot hybridization. The in vivo occupancy
      of liver somatogenic (GH) receptors was derived from the determinations of total
      and free 125I-labelled bGH binding to liver homogenates treated with 4 mol
      MgCl2/l or water. Injection of MAB-bGH complexes enhanced body weight gain and
      raised serum IGF-I, liver IGF-I and liver IGF-I mRNA more than bGH alone (1.6-, 6
      , 10- and 7-fold increases at the highest dose of MAB, compared with bGH alone; P
      < 0.001). These potentiating effects of the MAB were dose-dependent and
      significant potentiation of the growth response was already observed with the
      lowest dose of MAB. In vivo occupancy of liver GH receptors was markedly higher
      18 h after injection of MAB-bGH complexes than after bGH alone, and this effect
      was also dose-dependent (receptor occupancy of 28%, 37% and 83% after 4, 40 and
      400 micrograms of MAB respectively compared with 6% after bGH alone; P < 0.05,
      0.05 and 0.001 respectively). In contrast, the in vitro binding of 125I-labelled
      bGH to liver homogenates was decreased in the presence of high doses of MAB. We
      conclude that low amounts of MABs complexed with bGH potentiate the stimulation
      by the hormone of liver IGF-I synthesis and secretion in a dose-dependent manner.
      These effects are mediated, at least in part, through changes in hormone-receptor
      interaction in vivo, leading to enhanced and/or prolonged binding of bGH to its
      somatogenic receptors.

PMID- 8133208
TI  - Investigation of the ontogenetic patterns of rat hypothalamic dopaminergic
      neurone morphology and function in vitro.
AB  - Using fetal rat hypothalamic cells in primary culture maintained in a serum-free
      defined medium we have investigated the morphological and functional development
      of the dopamine (DA)-containing neurones intrinsic to the hypothalamus.
      Immunocytochemical studies demonstrated the presence of three morphologically
      distinct subtypes of tyrosine hydroxylase-immunopositive neurones. On day 3 in
      vitro unipolar, bipolar and multipolar cell types were apparent. The latter two
      subtypes persisted to later days in culture and increased both in perikarya size
      and neurite length. All subtypes have been shown to have correlates in vivo.
      Biochemical studies employing [3H]DA demonstrated a time- and temperature
      dependent uptake mechanism within the cultures which was significantly attenuated
      by the uptake inhibitors benztropine and nomifensine in a dose-dependent manner.
      [3H]DA was also released under both basal and 56 mmol K+/l-stimulated conditions
      and the magnitude of the response was reduced by exclusion of calcium from the
      release medium. The amount of [3H]DA accumulated and released by the cultural
      cells increased with the age of the culture, suggesting functional maturation of
      the DA-containing neurones within this preparation. The role of oestradiol-17
      beta in regulating hypothalamic dopaminergic function was also investigated both
      indirectly with the use of [3H]DA and by direct measurement of endogenously
      synthesized DA using high-performance liquid chromatography coupled with
      electrochemical detection. Both uptake and release of [3H] and release of
      endogenous DA were significantly modulated by the concentration of steroid in the
      defined medium. These results demonstrate that hypothalamic dopaminergic
      neurones, when maintained in primary culture, undergo morphological and
      functional maturation which have several correlates in vivo. In addition, we have
      demonstrated that at least one sub-population of dopaminergic neurones within
      this preparation is responsive to oestradiol-17 beta. As DA is considered to be a
      vital component in the regulation of neuroendocrine activity we suggest that this
      model is valuable for the investigation of the functional development of the DA
      systems of the hypothalamus and the relationship existing between
      neurotransmitters, neuropeptides and neuroactive steroids.

PMID- 8133209
TI  - The role of nitric oxide derived from L-arginine in the control of
      steroidogenesis, and perfusion medium flow rate in the isolated perfused rat
      adrenal gland.
AB  - The present studies were designed to investigate the role of nitric oxide (NO) in
      the regulation of adrenocortical function, using the intact rat adrenal gland in
      situ, perfused with medium (Hank's balanced salt solution) containing a range of
      concentrations of L-arginine, the substrate for NO production. In addition, the
      effects of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of NO
      production, were investigated. Results showed that L-arginine caused a dose
      dependent increase in the flow rate of the perfusion medium through the adrenal
      gland. This effect was specific, as neither D-arginine nor L-lysine had an
      effect. The presence of L-NAME (5 mmol/l) in perfusion medium containing L
      arginine caused a decrease in flow rate to levels in the absence of L-arginine.
      In the presence of concentrations of L-arginine up to 500 mumol/l, corticosterone
      secretion rates were also stimulated in a dose-dependent manner. Further studies,
      investigating the effect of L-arginine on the response to ACTH(1-24) stimulation,
      found that the percentage increase in flow rate, aldosterone secretion and
      corticosterone secretion caused by ACTH were not significantly different using
      media containing 230 mumol L-arginine/l or in the absence of L-arginine. These
      results suggest a role for NO derived from L-arginine in the regulation of basal
      levels of adrenal vascular tone in the rat isolated adrenal gland preparation.
      They do not suggest an obligatory role for NO in either the vascular or
      steroidogenic response to ACTH stimulation.

PMID- 8133210
TI  - Thyrotrophin-dependent desensitization by Chinese hamster ovary cells that
      express the recombinant human thyrotrophin receptor.
AB  - To determine whether thyrotrophin (TSH)-induced desensitization requires a
      thyroid-specific factor(s), the human TSH (hTSH) receptor was expressed in
      Chinese hamster ovary cells. The first incubation of the cells with TSH decreased
      the subsequent response of adenosine 3',5'-cyclic monophosphate to freshly added
      TSH in the second incubation. This homologous desensitization was observed as
      early as after 3 h of the first incubation. The lowest dose of TSH that elicited
      desensitization was 0.1 nmol/l. The desensitization was not overcome by adding
      higher doses of TSH in the second incubation. A 125I-labelled TSH-binding study
      revealed a decrease in the number of high-affinity binding sites but not in that
      of low-affinity binding sites. The data suggest that TSH-induced desensitization
      in hTSH receptor-transfected cells is caused, at least in part, by a decrease in
      the number of TSH receptors on the cell surface. The evidence demonstrates,
      contrary to an earlier report, that a thyroid-specific factor(s) is not required
      for hTSH receptor desensitization.

PMID- 8133211
TI  - Pharmacokinetic and galactopoietic response to recombinant variants of bovine
      growth hormone.
AB  - Two studies were designed to examine the pharmacokinetic and galactopoietic
      potency of three molecular variants of recombinant-derived bovine GH (rbGH):
      [Met1, Leu127]-bGH, [Ala1, Val127]-bGH and [Ala1, Val127, His133]-bGH. Histidine
      substitution for arginine at residue 133 of rbGH was shown to impart thrombin
      resistance. In a Latin square design, nine lactating Holstein cows received a 25
      mg rbGH bolus infusion via the jugular vein followed by frequent blood sampling
      over the next 12 h. The serum GH concentration data were found to fit a two
      compartment open model. Neither primary nor secondary kinetic parameter estimates
      differed significantly (P > 0.05) among the three rbGH variants. Thus, the
      disposition of GH concentration at time t was described by the equation C(t) =
      (1295.5 micrograms/l) (e-(0.11/min)(t)) + (317.3 micrograms/l)(e-(0.03/min)(t)).
      Overall averages were: area under the curve = 27.1 mg.min per l, clearance = 0.15
      litres/min per 100 kg and volume of distribution of the central compartment =
      2.59 litres/100 kg. The t 1/2 for the two compartments averaged 8.2 and 29.1 min.
      In the second study, 36 lactating Holstein cows received i.m. injections of one
      of four oil-based formulation treatments: control vehicle or 500 mg of one of the
      three rbGH variants every 14 days for 42 days. Average and maximum serum GH
      concentrations and area under the curve estimates were increased by approximately
      3-6 micrograms/l, 5-15 micrograms/l and 40-90 micrograms.day per 1 respectively.
      Ala1, Val127 rbGH treatments elicited greater blood GH concentrations than [Met1,
      Leu127]-bGH when administered in an oil-based formulation. Blood GH responses did
      not directly translate into milk response differences, possibly due to
      differences in biopotency or receptor availability. Thrombin resistance resulting
      from substitution of histidine at position 127 of rbGH did not affect blood GH
      pharmacokinetic parameters or milk response over other rbGH variants.

PMID- 8133212
TI  - Role of adenylate cyclase-cyclic AMP-dependent signal transduction in the ACTH
      induced biphasic growth effect of rat adrenocortical cells in primary culture.
AB  - ACTH has a biphasic effect on the proliferation of fetal rat adrenocortical cells
      in primary culture. Dramatic changes occurred during the first 72 h of ACTH
      stimulation, when incorporation of bromodeoxyuridine was used as an indicator of
      proliferation. The primary effect of ACTH was the inhibition of proliferation
      during the first 24 h, which was followed by an intense stimulatory phase during
      the third day of ACTH treatment. Cycloheximide (a protein synthesis inhibitor)
      prevented both the inhibitory and the stimulatory effects of ACTH, but did not
      affect the basal proliferation of unstimulated zona glomerulosa-like cells.
      Although adrenocortical cells stimulated with cyclic AMP (cAMP) derivatives, 8
      bromo cAMP (8-Br cAMP) or dibutyryl cAMP ((Bu)2cAMP), differentiated
      morphologically into fasciculata-like cells, and secreted corticosterone and 18
      OH-deoxycorticosterone, as did ACTH-stimulated cells, neither of the derivatives
      inhibited proliferation during the first 24 h of treatment. In contrast to ACTH,
      (Bu)2cAMP had a stimulatory effect on bromodeoxyuridine incorporation during the
      first 24 h of treatment. 8-Br cAMP did not change proliferation during the 24 h
      of treatment, but had a stimulatory effect after 72 h, which was not seen with
      (Bu)2cAMP. Thus, these results suggest that (1) differentiation, steroid hormone
      synthesis and the mitogenic effect of ACTH are transduced through the cAMP
      mediated system, (2) the antimitogenic effect of ACTH is transduced via a cAMP
      independent pathway and (3) both antimitogenic and mitogenic effects of ACTH are
      dependent on protein synthesis.

PMID- 8133213
TI  - Direct infusion of a variant of insulin-like growth factor-I into the skin of
      sheep and effects on local blood flow, amino acid utilization and cell
      replication.
AB  - In vivo effects of local infusion of a variant of insulin-like growth factor-I
      (IGF-I), long-R3-IGF-I, into the skin were investigated using six conscious sheep
      with food available ad libitum. An artery and vein on the abdominal flank of each
      animal, as well as the saphenous artery, were catheterized so that infusion of
      isotopically labelled amino acids, with or without IGF-I, could be used to
      determine amino acid uptake by arteriovenous difference in combination with blood
      flow determined by dye dilution. Measurements were made on each animal prior to
      IGF-I infusion, at hourly intervals for the 4 h of IGF-I infusion into the skin
      artery, then 2 and 4 h after IGF-I infusion ceased. Numbers of cells replicating
      in the bulbs of wool follicles in the IGF-I-infused area and in the skin on the
      contralateral side of each animal were measured after labelling with 5-bromo-2'
      deoxyuridine. IGF-I caused a significant increase in the skin blood flow (P <
      0.05), utilization of oxygen (P < 0.05), uptake of cysteine (P < 0.05) and
      phenylalanine (P < 0.001), and the rate of utilization of cysteine (P < 0.05) for
      protein synthesis. IGF-I increased amino acid uptake regardless of whether the
      skin was in negative or positive amino acid balance prior to infusion. During the
      recovery period amino acid utilization by skin returned towards preinfusion
      levels. No effects of IGF-I were found on replicating cell numbers in the bulbs
      of wool follicles.

PMID- 8133214
TI  - Maternal vitamin D status has no effect on the ontogeny of calcium-binding
      proteins in the duodenum, kidney and cerebellum of fetal mice.
AB  - The effects of vitamin D3 deficiency on the ontogeny of calcium-binding proteins
      (CaBPs) and the vitamin D receptor in the duodenum, kidney and cerebellum of the
      mouse were examined. Maternal vitamin D status did not affect the time of
      appearance of the fetal 28 kDa CaBP (CaBP-D28k) in the cerebellum, kidney and
      duodenum, and the 9 kDa CaBP (CaBP-D9k) in the intestine and kidney. Vitamin D
      receptor was undetectable in all fetal tissues, regardless of maternal vitamin D
      status, at all stages of gestation examined. Thus it appears that maternal
      vitamin D status does not affect the ontogeny of CaBP-D9k or CaBP-D28k in the
      mouse fetus. The factors that influence the appearance of calbindins in the fetus
      are unclear.

PMID- 8133215
TI  - Testosterone-induced compared with oestradiol-induced immunosuppression against
      Plasmodium chabaudi malaria.
AB  - Testosterone suppresses immunity against malaria caused by Plasmodium chabaudi in
      B10 mice. Since this effect is probably not mediated through the classical
      androgen-receptor response, we investigated whether testosterone might act, after
      aromatization to oestradiol (OE2), through the oestrogen receptor (ER). Indeed,
      OE2 was found to act immunosuppressively when used at only about 1% of the
      immunosuppressive dose of testosterone. This becomes evident as an OE2-induced
      suppression of self-healing of P. chabaudi infections in female and castrated
      male B10 mice. The immunosuppressive OE2 effect is associated with a 16-fold
      increase in the circulating level of OE2 and can be prevented by ER blockers such
      as tamoxifen and clomifene. In contrast, the immunosuppressive effect of
      testosterone, which is not associated with any changes in the level of OE2,
      cannot be abolished by ER blockers or by aromatase inhibitors, such as atamestane
      and drofazar hydrochloride. Moreover, OE2 and testosterone act differently on
      spleen cells; OE2 induces a decrease in CD(4+)-T-cells, whereas testosterone
      causes an increase in CD(8+)-T-cells and a decrease in total nucleated spleen
      cells. The immunosuppressive effect of testosterone, but not that of OE2, can be
      adoptively transferred to syngeneic mice by nucleated spleen cells, predominantly
      T-cells. Our data show that the immunosuppressive activity of testosterone, in
      contrast to OE2, is not mediated through the ER. The immunosuppressive action of
      testosterone is therefore thought to be primarily mediated through a non-genomic
      mechanism.

PMID- 8133217
TI  - Immunological activities of highly purified isoforms of human FSH correlate with
      in vitro bioactivities.
AB  - In a recent study, a five- to eightfold range in human FSH radioreceptor activity
      (RRA) was documented for highly purified isoforms of FSH when the data were
      expressed on an FSH protein content basis as determined by amino acid analysis.
      This study examined the FSH in vitro bioactivity and immunoactivity of these
      preparations. FSH in vitro biological activity showed a five- to eightfold range
      in activity with a high correlation with the RRA values (r = 0.82). A similar
      five- to eightfold range of values was obtained with a specific FSH
      radioimmunoassay and an FSH two-site immunoassay with high correlations again
      observed between each other, between each immunoassay and with either the in
      vitro bioassay or the RRA method (r = 0.77-0.995). Although there was overall a
      close correlation between these assays, significant differences in ratios of
      activities between the in vitro bioassay and other methods were observed with
      highly purified FSH isoform preparations from different pI regions. The high
      correlation between in vitro bioassay/RRA methods and immunoassay methods over a
      wide range of isoform specific activities suggests that these methods are
      detecting similar structural features on each isoform. It is thus concluded that
      these immunoassays are not solely measuring hormone mass based entirely on amino
      acid composition. This conclusion raises questions about ratio measurements of
      FSH, where immunoassay methods are presumed to measure total protein content, and
      their application in physiological situations and clinical practice.

PMID- 8133216
TI  - Immunohistochemical localization of 17 alpha-hydroxylase/C17-20 lyase and
      aromatase cytochrome P-450 in polycystic human ovaries.
AB  - Immunohistochemical localization of 17 alpha-hydroxylase/C17-20 lyase (P-450(17
      alpha,lyase)) and aromatase cytochrome P-450 (P-450arom) in polycystic ovary
      (PCO) syndrome was studied using specific polyclonal antibodies which had been
      raised against the corresponding enzymes. In the majority of follicles that were
      atretic and smaller than 7 mm in diameter, theca interna cells showed high P
      450(17 alpha,lyase) immunoreaction, while small numbers of granulosa cells showed
      little P-450arom immunoreaction. In some atretic follicles that were larger than
      11 mm in diameter, the hyperplastic theca interna cell layer showed high
      immunoreaction to P-450(17 alpha,lyase), while the poorly proliferated granulosa
      cell layer showed a mixture of weak and negative immunoreaction to P-450arom. No
      immunoreaction to P-450(17 alpha,lyase) or P-450arom was recognized in PCO
      stroma. These findings suggest that the theca interna cells and the granulosa
      cells from PCOs show abnormal steroidogenic function, while the localization of P
      450(17 alpha,lyase) and P-450arom in PCOs was essentially identical to that in
      the normal ovary. Theca interna cells in PCO atretic follicles are the main site
      of excess androgen production.

PMID- 8133218
TI  - Infants' perception of kinetic depth and stereokinetic displays.
AB  - Studies examined infants' perceptions of 3-dimensional form, using a kinetic
      depth effect (KDE) display and displays containing subsets of the motion present
      in the KDE display. One subset consisted of "between-contour" motion, and the
      second consisted of "within-contour" motion. Research with adults has suggested
      that only between-contour motion leads to a compelling depth percept. In
      Experiments 1 and 2, infants generalized habituation from a KDE display to the
      between-contour but not the within-contour changes. In Experiments 3 and 4,
      infants generalized habituation from a KDE display to the between-contour display
      viewed from a novel orientation but not to the within-contour display viewed from
      the original orientation. Results indicate sensitivity to between-contour but not
      within-contour information, suggesting that infants perceive the 3-dimensional
      form of these displays.

PMID- 8133219
TI  - Visual-auditory interactions in sensorimotor processing: saccades versus manual
      responses.
AB  - Reaction times (RTs) to bimodal (visual and auditory) stimuli were examined using
      3 different response systems: saccades, directed manual responses, and simple
      manual responses. The observed levels of intersensory facilitation exceeded race
      model predictions and therefore support summation (coactivation) models of
      bimodal processing. However, response-dependent differences suggest that the
      processing of bimodal targets also depends on the relevant sensorimotor pathways
      and requirements of the task. Coactivation of response mechanisms might account
      for the effects found using simple RTs. The results for saccades are consistent
      with known patterns of auditory-visual convergence in the oculomotor system.

PMID- 8133220
TI  - Affordances, perceptual complexity, and the development of tool use.
AB  - Perceiving the affordance of a tool requires the integration of several
      complementary relationships among actor, tool, and target. Highers order
      affordance structures are introduced to deal with these forms of complex action
      from an ecological-realist point of view. The complexity of the higher order
      affordance structure was used to predict the difficulty of perceiving the tool
      function. Predictions were tested in 3 experiments involving children between 9
      months and 4 years old. In a classical tool use task dating back to W. Kohler, a
      desirable target was obtained by using a hook as a tool. The relative positions
      of the hook and the target were systematically varied to obtain structures
      differing in complexity. The observed difficulty of the task was found
      essentially in accordance with the theoretical complexity of the higher order
      affordance structures involved in perceiving the tool function.

PMID- 8133222
TI  - Visual attention and objects: one versus two or convex versus concave?
AB  - According to object-based theories of visual attention, attention can be divided
      within a single object more efficiently than between separate objects (J. Duncan,
      1984). Recently, G. C. Baylis and J. Driver (1993) provided a theoretical
      framework for interpreting this single-object advantage within the domain of
      spatial organization. Using their hierarchical coding of location hypothesis,
      they showed that the latency to compare the location of 2 vertices was
      significantly faster for vertices that were seen as part of a single (convex)
      object than for vertices that were seen as parts of separate (concave) objects.
      This article reports the replication of this finding, as well as new evidence
      that shows that latency is affected by the convexity of the contour, and not by
      the number of objects.

PMID- 8133221
TI  - Lexical involvement in naming does not contravene prelexical phonology: comment
      on Sebastian-Galles (1991).
AB  - N. Sebastian-Galles (1991) showed lexical involvement in naming Spanish. Her
      results were purported to be a failure to substantiate claims for prelexical
      phonology that characterize Serbo-Croatian. Summaries of several experimental
      demonstrations of lexical involvement in naming Serbo-Croatian are used to show
      that such results are only interpretable consistently in a model that assumes
      prelexical phonology. The lexicon is accessed through assembled phonology, but
      assembled and lexical phonology interact in resolving a unique pronunciation when
      several pronunciations are assembled and in assigning stress, which is not
      assembled. The authors argue that lexical access need not be different in
      different orthographies but that the weights on connections between orthographic
      and phonological substructures established through covariant learning will
      distinguish orthographies in the rate and degree of phonological involvement in
      word recognition.

PMID- 8133223
TI  - The nonlinear dynamics of speech categorization.
AB  - Little is known about the processes underlying the nonlinear relationship between
      acoustics and speech perception. In Experiment 1, we explored the effects of
      systematic variation of a single acoustic parameter (silent gap duration between
      a natural utterance of s and a synthetic vowel ay) on judgements of speech
      category. The resulting shifts in category boundary between say and stay showed
      rich dynamics, including hysteresis, contrast, and critical boundary effects. We
      propose a dynamical model to account for the observed patterns. Experiment 2
      evaluated one prediction of the model, that changing the relative stability of
      the two percepts allows categorical switching. In agreement with the model; an
      increase in the number of stimulus repetitions maximized the frequency of
      judgments of category change near the boundary. Thus, a dynamical approach
      affords the rudiments for a theory of the effects of temporal context on speech
      categorization.

PMID- 8133224
TI  - A theory of visual information acquisition and visual memory with special
      application to intensity-duration trade-offs.
AB  - We describe a theory of memory for visual material in which the visual system
      acts as a linear filter operating on a stimulus to produce a function, a(t),
      relating some sensory response to t (the time since stimulus onset). Stimulus
      information is acquired at a rate proportional to the product of the magnitude by
      which a(t) exceeds some threshold, and the amount of as-yet-unacquired
      information. Recall performance is assumed to equal the proportion of acquired
      information. The theory accounts for data from 2 digit-recall experiments in
      which stimulus temporal waveform was manipulated. We comment on the theory's
      account of the relation between 2 perceptual events: the phenomenological
      experience of the stimulus, and the memory representation that accrues from
      stimulus presentation. We assert that these 2 events, although influenced by
      different variables, can be viewed as resulting from 2 characteristics of the
      same sensory-response function.

PMID- 8133225
TI  - Attention to orientation, size, luminance, and color: attentional failure within
      the form domain.
AB  - Whether Ss can attend to physical dimensions of objects without access to
      semantic information about them was examined. Ss decided which of 2 laterally
      presented pictures, a target and a distractor, had the same orientation
      (Experiment 1), size (Experiment 2), luminance (Experiment 3), or color
      (Experiment 4) as a reference picture. In each experiment, the matching stimuli
      were either physically identical, semantically related, or semantically
      unrelated. The reference stimulus and the distractor were either semantically
      related or unrelated. When matching was based on orientation or on size,
      performance was facilitated when the matching stimuli were semantically related,
      and it was disrupted when the distractor was semantically related to the
      reference stimulus. Semantic effects were eliminated when matching was based on
      luminance or color. The results are discussed in terms of physiological data,
      form and surface information, and global and local processing.

PMID- 8133226
TI  - Stages of auditory feature conjunction: an event-related brain potential study.
AB  - Auditory event-related brain potentials (ERPs) were recorded to tones of
      different frequencies and locations in a dichotic selective attention task in
      which Ss responded to occasional deviant tones of a prespecified location and
      frequency. Attention effects were isolated as negative difference (Nd) waves by
      subtracting ERPs to tones with no attended features from ERPs to the same tones
      when they shared target frequency, location, or both cues. The N1/P90 (latency 80
      100 ms), originating in a tonotopically organized generator, was enhanced for all
      tones in the attended ear. Nd waves, beginning at 80 ms and lasting up to 700 ms,
      were seen to tones with either attended feature. Nd waves to frequency and
      location features had different scalp distributions consistent with generation in
      different cortical fields. Conjunction-specific Nds began 30-50 ms after Nds to
      individual features. The relative timing suggests that feature conjunction began
      before the analysis of individual features was complete.

PMID- 8133227
TI  - Stimulus-driven attentional capture: evidence from equiluminant visual objects.
AB  - Previous work has shown that abrupt visual onsets capture attention. Possible
      attention. Possible mechanisms for this phenomenon include (a) a luminance-change
      detection system and (b) a mechanism that detects the appearance of new
      perceptual objects. Experiments 1 and 2 revealed that attention is captured in
      visual search by the appearance of a new perceptual object even when the object
      is equiluminant with its background and thus exhibits no luminance change when it
      appears. Experiment 3 showed that a highly salient luminance increment alone is
      not sufficient to capture attention. These findings suggest that attentional
      capture is mediated by a mechanism that detects the appearance of new perceptual
      objects.

PMID- 8133228
TI  - Medical law and ethics. From training to education.

PMID- 8133229
TI  - Withdrawing life support and advance directives. Medical aspects.

PMID- 8133230
TI  - Advance directives and treatment withdrawal. Legal considerations.

PMID- 8133231
TI  - Use of anencephalics as organ donors.

PMID- 8133232
TI  - Do-not-resuscitate orders.
AB  - CPR is a procedure from which approximately 15% of patients survive to discharge.
      Patients have the right to request DNR orders and health professionals have an
      obligation to provide the information to make decisions. Physicians and patients
      should discuss advance directives before hospital admission. Patients without
      decision-making capacity are dependent on advance directives, surrogates or
      proxies for DNR orders. The most recent version of the Florida statute has
      improved the procedural mechanism for writing DNR orders but continues to need
      further refinement.

PMID- 8133233
TI  - HIV testing. Informed consent and confidentiality.

PMID- 8133234
TI  - The future of the "right to die".

PMID- 8133235
TI  - Development of hospital ethics committees.

PMID- 8133236
TI  - Oxidant-induced alterations of lung surfactant system.
AB  - Lung surfactant is subject to oxidant injury from inhaled pollutants and free
      radicals generated by activated leukocytes in various disease states. Both lipid
      and protein components of surfactant can be altered by oxygen radicals. Changes
      were investigated in the lung surfactant system using a rat model with ozone
      injury to simulate adult respiratory distress syndrome, in which surfactant
      activity is thought to be inadequate. A significant decrease in dynamic lung
      compliance was correlated with the accumulation of protein in the alveolar lavage
      fluid. The amount of dipalmitoylphosphatidylcholine, the most abundant
      phospholipid in surfactant, increased two-fold indicating that the acute changes
      in lung function were related to the inactivation of surfactant by edema fluid
      and not to a quantitative lack of surfactant phospholipids. The amount of
      surfactant stored in lamellar bodies of the alveolar type II cells also increased
      and was abnormal in composition. The amount of cholesterol and albumin increased
      following ozone stress, suggesting that an altered uptake and incorporation of
      alveolar components into the lamellar bodies may be an important process in
      oxidant-induced lung injury. In contrast, lysozyme, an abundant protein in the
      alveolar fluid and lamellar bodies, rapidly decreased in concentration in the
      intracellular surfactant. Using an in vitro system we found that lysozyme is very
      sensitive to ozone injury and may function as a "sacrificial" antioxidant in the
      alveolar lining fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133238
TI  - Death by a thousand paper cuts.

PMID- 8133237
TI  - An employment law primer.

PMID- 8133239
TI  - Ca(2+)-dependent inactivation of cardiac L-type Ca2+ channels does not affect
      their voltage sensor.
AB  - Inactivation of currents carried by Ba2+ and Ca2+, as well as intramembrane
      charge movement from L-type Ca2+ channels were studied in guinea pig ventricular
      myocytes using the whole-cell patch clamp technique. Prolonged (2 s) conditioning
      depolarization caused substantial reduction of charge movement between -70 and 10
      mV (charge 1, or charge from noninactivated channels). In parallel, the charge
      mobile between -70 and -150 mV (charge 2, or charge from inactivated channels)
      was increased. The availability of charge 2 depended on the conditioning pulse
      voltage as the sum of two Boltzmann components. One component had a central
      voltage of -75 mV and a magnitude of 1.7 nC/microF. It presumably is the charge
      movement (charge 2) from Na+ channels. The other component, with a central
      voltage of approximately -30 mV and a magnitude of 3.5 nC/microF, is the charge 2
      of L-type Ca2+ channels. The sum of charge 1 and charge 2 was conserved after
      different conditioning pulses. The difference between the voltage dependence of
      the activation of L-type Ca2+ channels (half-activation voltage, V, of
      approximately -20 mV) and that of charge 2 (V of -100 mV) made it possible to
      record the ionic currents through Ca2+ channels and charge 2 in the same
      solution. In an external solution with Ba2+ as sole metal the maximum available
      charge 2 of L-type Ca2+ channels was 10-15% greater than that in a Ca(2+)
      containing solution. External Cd2+ caused 20-30% reduction of charge 2 both from
      Na+ and L-type Ca2+ channels. Voltage- and Ca(2+)-dependent inactivation
      phenomena were compared with a double pulse protocol in cells perfused with an
      internal solution of low calcium buffering capacity. As the conditioning pulse
      voltage increased, inactivation monitored with the second pulse went through a
      minimum at about 0 mV, the voltage at which conditioning current had its maximum.
      Charge 2, recorded in parallel, did not show any increase associated with calcium
      entry. Two alternative interpretations of these observations are: (a) that Ca(2+)
      dependent inactivation does not alter the voltage sensor, and (b) that
      inactivation affects the voltage sensor, but only in the small fraction of
      channels that open, and the effect goes undetected. A model of channel gating
      that assumes the first possibility is shown to account fully for the experimental
      results. Thus, extracellular divalent cations modulate voltage-dependent
      inactivation of the Ca2+ channel. Intracellular Ca2+ instead, appears to cause
      inactivation of the channel without affecting its voltage sensor.

PMID- 8133240
TI  - Odorant receptors activated by amino acids in sensory neurons of the channel
      catfish Ictalurus punctatus.
AB  - Odorant receptors activated by amino acids were investigated with patch-clamp
      techniques in olfactory receptor neurons of the channel catfish, Ictalurus
      punctatus. The L-isomers of alanine, norvaline, arginine, and glutamate, known to
      act predominantly on different olfactory receptor sites, activated
      nondesensitizing inward currents with amplitudes of -2.5 to -280 pA in olfactory
      neurons voltage-clamped at membrane potentials of -72 or -82 mV. Different amino
      acids were shown to induce responses in the same sensory neurons; however, the
      amplitude and the kinetics of the observed whole cell currents differed among the
      stimuli and may therefore reflect activation of different amino acid receptor
      types or combinations of receptor types in these cells. Amino acid-induced
      currents appeared to have diverse voltage dependence and could also be classified
      according to the amplitude of the spontaneous channel fluctuations underlying the
      macroscopic currents. A mean single-channel conductance (gamma) of 360 fS was
      estimated from small noise whole-cell currents evoked by arginine within the same
      olfactory neuron in which a mean gamma value of 23.6 pS was estimated from 'large
      noise' response to norvaline. Quiescent olfactory neurons fired bursts of action
      potentials in response to either amino acid stimulation or application of 8-Br
      cyclic GMP (100 microM), and voltage-gated channels underlying generation of
      action potentials were similar in these neurons. However, in whole-cell voltage
      clamp, 8-Br-cyclic GMP evoked large rectangular current pulses, and single
      channel conductances of 275, 220, and 110 pS were obtained from the discrete
      current levels. These results suggest that in addition to the cyclic nucleotide
      gated transduction channels, olfactory neurons of the channel catfish possess a
      variety of odor receptors coupled to different types of transduction channels.

PMID- 8133241
TI  - Probing the structure of the conduction pathway of the sheep cardiac sarcoplasmic
      reticulum calcium-release channel with permeant and impermeant organic cations.
AB  - The sarcoplasmic reticulum Ca(2+)-release channel plays a central role in cardiac
      muscle function by providing a ligand-regulated pathway for the release of
      sequestered Ca2+ to initiate contraction following cell excitation. The
      efficiency of the channel as a Ca(2+)-release pathway will be influenced by both
      gating and conductance properties of the system. In the past we have investigated
      conduction and discrimination of inorganic mono- and divalent cations with the
      aim of describing the mechanisms governing ion handling in the channel (Tinker,
      A., A.R. G. Lindsay, and A.J. Williams. 1992. Journal of General Physiology.
      100:495-517.). In the present study, we have used permeant and impermeant organic
      cations to provide additional information on structural features of the
      conduction pathway. The use of permeant organic cations in biological channels to
      explore structural motifs underlying selectivity has been an important tool for
      the electrophysiologist. We have examined the conduction properties of a series
      of monovalent organic cations of varying size in the purified sheep cardiac
      sarcoplasmic reticulum Ca(2+)-release channel. Relative permeability, determined
      from the reversal potential measured under bi-ionic conditions with 210-mM test
      cation at the cytoplasmic face of the channel and 210 mM K+ at the luminal, was
      related inversely to the minimum circular cation radius. The reversal potential
      was concentration-independent. The excluded area hypothesis, with and without a
      term for solute-wall friction, described the data well and gave a lower estimate
      for minimum pore radius of 3.3-3.5 A. Blocking studies with the impermeant
      charged derivative of triethylamine reveal that this narrowing occurs over the
      first 10-20% of the voltage drop when crossing from the lumen of the SR to the
      cytoplasm. Single-channel conductances were measured in symmetrical 210 mM salt.
      Factors other than relative permeability determine conductance as ions with
      similar relative permeability can have widely varying single-channel conductance.
      Permeant ions, such as the charged derivatives of trimethylamine and
      diethylmethylamine, can also inhibit K+ current. The reduction in relative
      conductance with increasing concentrations of these two ions at a holding
      potential of 60 mV was described by a rectangular hyperbola and revealed higher
      affinity binding for diethylmethylamine as compared to trimethylamine. It was
      possible to describe the complex permeation properties of these two ions using a
      single-ion four barrier, three binding site Eyring rate theory model. In
      conclusion, these studies reveal that the cardiac Ca(2+)-release channel has a
      selectivity filter of approximately 3.5-A radius located at the luminal face of
      the protein.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8133242
TI  - Influenza hemagglutinin-mediated fusion pores connecting cells to planar
      membranes: flickering to final expansion.
AB  - We have studied the fusion between voltage-clamped planar lipid bilayers and
      influenza virus infected MDCK cells, adhered to one side of the bilayer, using
      measurements of electrical admittance and fluorescence. The changes in currents
      in-phase and 90 degrees out-of-phase with respect to the applied sinusoidal
      voltage were used to monitor the addition of the cell membrane capacitance to
      that of the lipid bilayer through a fusion pore connecting the two membranes.
      When ethidium bromide was included in the solution of the cell-free side of the
      bilayer, increases in cell fluorescence accompanied tee admittance changes,
      independently confirming that these changes were due to formation of a fusion
      pore. Fusion required acidic pH on the cell-containing side and depended on
      temperature. For fusion to occur, the influenza hemagglutinin (HA) had to be
      cleaved into HA1 and HA2 subunits. The incorporation of gangliosides into the
      planar bilayers greatly augmented fusion. Fusion pores developed in four distinct
      stages after acidification: (a) a pre-pore, electrically quiescent stage; (b) a
      flickering stage, with 1-2 nS pores opening and closing repetitively; (c) an
      irreversibly opened stage, in which pore conductances varied between 2 and 100 nS
      and exhibited diverse kinetics; (d) a fully opened stage, initiated by an
      instantaneous, time-resolution limited, increase in conductance leveling at
      approximately 500 nS. The expansion of pores by stages has also been shown to
      occur during exocytosis in mast cells and fusion of HA-expressing cells and
      erythrocytes. We conclude that essential features of fusion pores are produced
      with proteins in just one of the two fusing membranes.

PMID- 8133243
TI  - Influenza virus hemagglutinin-induced cell-planar bilayer fusion: quantitative
      dissection of fusion pore kinetics into stages.
AB  - Cells expressing the influenza virus hemagglutinin (HA) fuse to planar bilayer
      membranes under acidic conditions. After an electrically quiescent perfusion
      stage (Q), a fusion pore forms that enlarges in three subsequent stages. A
      repetitively flickering pore stage (R) develops into a securely open stage (S)
      that exhibits conductances ranging from a few to tens of nS. The pore then
      expands to a terminal stage (T) with a large conductance on the order of one
      microSiemens. We have studied how virus strain, HA receptors in the target
      bilayer membrane, and cytoskeleton affect the time a fusion pore remains in each
      stage. These intervals are referred to as waiting times. In the quiescent stage,
      waiting times were very sensitive to the virus strain and presence of
      gangliosides (HA receptors) in the bilayer. When bilayers contained gangliosides,
      the waiting times in the Q stage for cells infected with the PR/8/34 strain of
      virus were exponentially distributed, whereas waiting times for cells infected
      with the Japan/305/57 strain were not so distributed. Without gangliosides, the
      waiting time distribution for PR/8/34 infected cells was complex. The waiting
      times in the R and S stages of pore growth were exponentially distributed under
      all tested conditions. Within the R stage, we analyzed the kinetics of the
      flickering pore by fitting the open and closed time distributions with a sum of
      two exponentials. Neither the open and closed time distributions nor the
      flickering pore conductance distributions were appreciably affected by virus
      strain or gangliosides. Colchicine and cytochalasin B increased the flicker
      rates, without affecting the waiting time in the R stage. We conclude that
      variations in amino acid sequences of the HAs and the presence of gangliosides as
      receptors within the target membrane critically affect the kinetics of fusion
      pore formation, but do not affect subsequent stages.

PMID- 8133244
TI  - Effect of basolateral CO2/HCO3- on intracellular pH regulation in the rabbit S3
      proximal tubule.
AB  - We used the absorbance spectrum of the pH-sensitive dye
      dimethylcarboxyfluorescein to monitor intracellular pH (pHi) in the isolated
      perfused S3 segment of the rabbit proximal tubule, and examined the effect on pHi
      of switching from a HEPES to a CO2/HCO3- buffer in the lumen and/or the bath
      (i.e., basolateral solution). Solutions were titrated to pH 7.40 at 37 degrees C.
      With 10 mM acetate present bilaterally (lumen and bath), this causing steady
      state pHi to be rather high (approximately 7.45), bilaterally switching the
      buffer from 32 mM HEPES to 5% CO2/25 mM HCO3- caused a sustained fall in pHi of
      approximately 0.26. However, with acetate absent bilaterally, this causing steady
      state pHi to be substantially lower (approximately 6.9), bilaterally switching to
      CO2/HCO3- caused a transient pHi fall (due to the influx of CO2), followed by a
      sustained rise to a level approximately 0.18 higher than the initial one. The
      remainder of the experiments was devoted to examining this alkalinization in the
      absence of acetate. Switching to CO2/HCO3- only in the lumen caused a sustained
      pHi fall of approximately 0.15, whereas switching to CO2/HCO3- only in the bath
      caused a transient fall followed by a sustained pHi increase to approximately
      0.26 above the initial value. This basolateral CO2/HCO3(-)-induced alkalinization
      was not inhibited by 50 microM DIDS applied shortly after CO2/HCO3- washout, but
      was slowed approximately 73% by DIDS applied more than 30 min after CO2/HCO3-
      washout. The rate was unaffected by 100 microM bilateral acetazolamide, although
      this drug greatly reduced CO2-induced pHi transients. The alkalinization was not
      blocked by bilateral removal of Na+ per se, but was abolished at pHi values below
      approximately 6.5. The alkalinization was also unaffected by short-term bilateral
      removal of Cl- or SO4=. Basolateral CO2/HCO3- elicited the usual pHi increase
      even when all solutes were replaced, short or long-term (> 45 min), by N-methyl-D
      glucammonium/glucuronate (NMDG+/Glr-). Luminal CO2/HCO3- did not elicit a pHi
      increase in NMDG+/Glr-. Although the sustained pHi increase elicited by
      basolateral CO2/HCO3- could be due to a basolateral HCO3- uptake mechanism, net
      reabsorption of HCO3- by the S3 segment, as well as our ACZ data, suggest instead
      that basolateral CO2/HCO3- elicits the sustained pHi increase either by
      inhibiting an acid-loading process or stimulating acid extrusion across the
      luminal membrane (e.g., via an H+ pump).

PMID- 8133245
TI  - Interactions of amino terminal domains of Shaker K channels with a pore blocking
      site studied with synthetic peptides.
AB  - Synthetic peptides of the five alternative NH2-terminal sequences of Shaker when
      applied to the cytoplasmic side of ShB channels that have an NH2-terminal
      deletion (ShB delta 6-46) block the channel with potencies correlated with the
      rate of inactivation in the corresponding variant. These peptides share no
      sequence similarity and yet three out of the five have apparent dissociation
      constants between 2 and 15 microM, suggesting that the specificity requirements
      for binding are low. To identify the primary structural determinants required for
      effective block of ShB delta 6-46, we examined the effects of substitutions made
      to the 20 residue ShB peptide on association and dissociation rates. Nonpolar
      residues within the peptide appear to be important in stabilizing the binding
      through hydrophobic interactions. Substitutions to leucine-7 showed there was a
      clear correlation between hydrophobicity and the dissociation rate constant
      (koff) with little effect on the association rate constant (kon). Substituting
      charged residues for hydrophobic residues within the region 4-8 disrupted
      binding. Within the COOH-terminal half of the peptide, substitutions that
      increased the net positive charge increased kon with relatively small changes in
      koff, suggesting the involvement of long-range electrostatic interactions in
      increasing the effective concentration of the peptide. Neutralizing charged
      residues produced small changes in koff. Charges within the region 12-20 act
      equivalently; alterations which conserved net charge produced little effect on
      either kon or koff. The results are consistent with this region of the peptide
      having an extended conformation and suggest that when bound this region makes few
      contacts with the channel protein and remains relatively unconstrained. Analogous
      mutations within the NH2-terminal domain of the intact ShB channel produced
      qualitatively similar effects on blocking and unblocking rates.

PMID- 8133246
TI  - Energetics of Shaker K channels block by inactivation peptides.
AB  - A synthetic peptide of the NH2-terminal inactivation domain of the ShB channel
      blocks Shaker channels which have an NH2-terminal deletion and mimics many of the
      characteristics of the intramolecular inactivation reaction. To investigate the
      role of electrostatic interactions in both peptide block and the inactivation
      process we measured the kinetics of block of macroscopic currents recorded from
      the intact ShB channel, and from ShB delta 6-46 channels in the presence of
      peptides, at different ionic strengths. The rate of inactivation and the
      association rate constants (k(on)) for the ShB peptides decreased with increasing
      ionic strength. k(on) for a more positively charged peptide was more steeply
      dependent on ionic strength consistent with a simple electrostatic mechanism of
      enhanced diffusion. This suggests that a rate limiting step in the inactivation
      process is the diffusion of the NH2-terminal domain towards the pore. The
      dissociation rates (k(off)) were insensitive to ionic strength. The temperature
      dependence of k(on) for the ShB peptide was very high, (Q10 = 5.0 +/- 0.58),
      whereas k(off) was relatively temperature insensitive (Q10 approximately 1.1).
      The results suggest that at higher temperatures the proportion of time either the
      peptide or channel spends in the correct conformation for binding is increased.
      There were two components to the time course of recovery from block by the ShB
      peptide, indicating two distinct blocked states, one of which has similar
      kinetics and dependence on external K+ concentration as the inactivated state of
      ShB. The other is voltage-dependent and at -120 mV is very unstable. Increasing
      the net charge on the peptide did not increase sensitivity to knock-off by
      external K+. We propose that the free peptide, having fewer constraints than the
      tethered NH2-terminal domain binds to a similar site on the channel in at least
      two different conformations.

PMID- 8133247
TI  - Interaction of cobalt ions with carboxypeptidase A.
AB  - The interaction of cobalt(II) with native and cobalt(II)-substituted
      carboxypeptidase has been investigated, at pH 7.5, by electronic absorption and
      1H NMR spectroscopies. The reaction of the cobalt(II) uptake by the metalloenzyme
      [MCPA] (M = Zn or Co) occurs very slowly and a bimetallic complex, [MCPA(Co)], is
      formed. On the basis of the 1H NOE experiments, the isotropically shifted proton
      resonances were assigned as belonging to a coordinated histidine residue. 1H NMR
      titrations of [ZnCPA(Co)] with zinc(II) show that the zinc ion does not compete
      with cobalt for binding to the noncatalytic site. The temperature dependence of
      the isotropic shifts, molar absorbance, and longitudinal relaxation time values
      are indicative of a five-coordinated geometry for the cobalt ion. The
      identification of the noncatalytic cobalt binding site is also discussed.

PMID- 8133248
TI  - Synthesis, spectroscopic and structural characterization, and biological activity
      of aquachloro (pyridoxal thiosemicarbazone) copper(II) chloride.
AB  - The synthesis, spectroscopic studies, x-ray crystal structure, and biological
      properties of the complex [Cu(H2L)(OH2)Cl]Cl (1) (H2L = pyridoxal
      thiosemicarbazone) are reported. The compound crystallizes in space group
      P2(1)/n, a = 12.128(2), b = 9.096(2), c = 13.592(2) A, beta = 108.65(2) degrees,
      U = 1420.7 A3, and Z = 4. The molecular structure consists of discrete cations
      [Cu(H2L)(OH2)Cl]+ and Cl- anions. Each copper atom is in an approximately square
      pyramidal environment involving the phenolic oxygen, the imine nitrogen, the
      sulphur, and a water oxygen in the equatorial positions, while a chlorine atom
      occupies the axial position. The structure of this complex is compared to that of
      the dimeric [(Cu(HL)(OH2))2]Cl2.2H2O (2) obtained under different experimental
      conditions, to that of a Co(III) complex with the same ligand [Co(HL)L].4.5H2O
      (3) and to that of the free ligand H2L, especially in relation to its biological
      activity. Compounds 1 and 2 have not antiviral action in vitro with respect to
      RNA viruses, show an inductive effect on Friend erythroleukemia cells (FLC),
      erythroid differentiation and a suppressive effect regarding FLC proliferation.
      Complex 3 and the free ligand do not have biological activity.

PMID- 8133249
TI  - Effects of copper on rat hepatoma HTC cells and primary cultured rat hepatocytes.
AB  - Cellular responses to copper, applied in concentrations varying from 0.5 to 200
      microM Cu2+, were investigated in two different cell types: rat hepatoma cells
      (HTC) and primary cultured rat hepatocytes. Accumulation of 64Cu, copper (AAS)
      levels, cellular viability parameters (cell growth and proliferation, LDH
      leakage, total cell protein, K+ uptake, and ATP levels), and cell toxicity
      parameters (metallothionein (MT), glutathione (GSH) and superoxide dismutase
      (SOD)) were examined over 24 hr incubation periods. Accumulation of radiolabeled
      copper (applied copper concentrations: 15-200 microM Cu2+) showed a four-fold
      increase in HTC cells (0.88-3.45 nmol Cu/mg cell protein) and a three-fold
      increase in hepatocytes (4.94-14.66 nmol Cu/mg cell protein), although
      quantitative uptake in HTC cells was five times lower. Most of the copper
      accumulated in the hepatoma cells and hepatocytes was found predominantly in the
      particulate fraction (i.e., cell membranes and organelles), while only a small
      quantity was present in the soluble fraction (cell cytosol). Metallothionein
      concentrations in HTC cells were increased from 43 pmol/mg cell protein (0.5
      microM Cu2+ application) up to 223 pmol/mg cell protein (200 microM Cu2+
      application), whereas MT in rat hepatocytes were elevated from 139 pmol/mg cell
      protein to 546 pmol/mg cell protein over the same range of administered Cu2+.
      Metallothionein synthesis rendered both cell types well equipped to deal with
      increasing intracellular copper levels. In hepatocytes however, MT synthesis
      resulted in decreasing non-MT-associated copper levels in the cytosol for Cu
      administrations up to 100 microM. Above that point however, MT failed to stay in
      line with increasing cytosolic Cu levels, resulting in cytotoxic effects shown by
      changes in cell viability and GSH/SOD levels. In HTC cells MT synthesis
      suppressed the free Cu levels in the cytosol to below 0.1 nmol Cu/mg cell protein
      over the total range of copper concentrations applied. The results presented
      indicate that hepatoma HTC cells are more capable of dealing with high
      accumulated Cu levels than the better established rat hepatocytes. Furthermore,
      it is clear that comparison of these two cell types regarding their ability to
      respond on (sub)toxic Cu should be discussed with full consideration for the
      copper applications involved.

PMID- 8133250
TI  - Synthesis and spectroscopy studies of copper(II) nitrate of sulfacetamide drug.
      Crystal structure of [Cu(sulfacetamide)2(NO3)2]. Antibacterial studies.
AB  - The structural spectroscopic, and thermal properties of a complex of
      sulfacetamide (Hsacm) with Cu(II) have been investigated. The complex
      [Cu(Hsacm)2(NO3)2] crystallizes in the monoclinic system, space group P2(1)/n.
      The cell dimensions are a = 7.696(7) A, b = 8.017(7) A, c = 19.230(10), beta =
      110.80(1) degree, V = 1109(1) A3, Z = 2, and Dx = 1.84 g/cm3. The structure was
      refined to R = 0.0776. Cu(Hsacm)2(NO3)2 molecules form a long polymeric chain
      extended along the b-axis. The copper(II) coordinated geometry is tetragonally
      distorted octahedral with two amino nitrogens from Hsacm and two oxygens from
      nitrato anions in the basal plane and two acetamido oxygens from neighbor Hsacm
      molecules in the apical position. Each sulfacetamide, acting as a bidentate
      ligand, links two Cu(II) ions as a bridge through the Namino and the Oacetamido
      atoms. The complex proved to possess higher bacteriostatic activity than the
      corresponding ligand.

PMID- 8133251
TI  - Effect of lanthanide ions on the phase behavior of dipalmitoylphosphatidylcholine
      multilamellar liposomes.
AB  - The effect of lanthanide ions (Ln3+) and their coordination compounds of
      diethylenetriamine pentaacetic acid (DTPA) on the phase behavior of
      dipalmitoylphosphatidylcholine (DPPC) multi-lamellar liposomes has been studied
      by differential scanning calorimetry (DSC), Raman spectroscopy, and freeze
      fracture electron microscopic techniques. The displacement of Ca2+ binding on
      DPPC liposomes by lanthanide ions was also studied. The results show that the
      binding degree of four kinds of chloride salts with DPPC liposomes is: YbCl3 >
      GdCl3 > LaCl3 > CaCl2. Lanthanide ions increase the phase transition temperature
      of DPPC liposomes and decrease the membrane fluidity. Freeze-fracture electron
      microscopic results show that La3+ enhances the order of DPPC membrane. The
      effect of coordination compounds of lanthanides with DTPA on the phase behavior
      of DPPC liposomes is smaller than that of their chlorides. La3+, Gd3+, and Yb3+,
      can displace Ca2+ binding on DPPC liposomes, but there coordination compounds of
      DTPA can hardly displace Ca2+. Raman spectroscopic results show that a very
      slight effect in lateral packing order of DPPC liposomes was observed at various
      concentrations of lanthanides.

PMID- 8133252
TI  - Haem peptide/protein interaction. Part 6: The kinetic mechanisms of the
      interactions with, and inhibition of enzymic activity of the human erythrocyte
      glutathione S-transferase isoenzyme rho (p), by haem octa-, nona-, and
      undecapeptides MP-8/-9/-11.
AB  - The binding of the cytochrome-c derived haem peptides microperoxidase-8, -9, and 
      11 (MP-8, -9, and -11) to the human erythrocyte glutathione S-transferase rho
      (GST-p) enzyme is demonstrated. Inhibition by the haem peptides of the enzymic
      conjugation of glutathione (GSH) with the electrophilic cosubstrate 1-chloro-2, 4
      dinitrobenzene (CDNB) is mixed-type with respect to CDNB, and Ki, the inhibition
      constant, increases with increasing length of the peptide chain. The results
      obtained here for the GST-p are compared to those published recently for the
      previously-supposed identical isoenzyme human placental GST-pi.

PMID- 8133253
TI  - Cesium uptake studies on human erythrocytes.
AB  - The uptake of Cs+ ions into the erythrocytes of abstemious volunteers and of
      alcoholic patients was followed using 133Cs NMR. The uptake rates are
      approximately linear with a rate of 0.33 mM.h-1 at an extracellular Cs+
      concentration of 10 mM. There is no discernible difference in the uptake rate
      between the two classes of subject despite earlier reports that Cs+ distribution
      is different and consequently that Cs+ transport might be anomalous in
      alcoholics. There is no evidence of saturation of the input rate and Cs(+)-loaded
      cells retain their Cs+ when incubated in a Cs(+)-free buffer, strongly suggesting
      that there is no transport mechanism for the removal of Cs+ from the erythrocyte.
      Experiments designed to ascertain which intracellular ion is being replaced by
      Cs+ indicate that it predominantly displaces K+.

PMID- 8133254
TI  - Platinum (II) and (IV) spermidine complexes. Synthesis, characterization, and
      biological studies.
AB  - By reaction of K2PtCl4 with spermidine we have synthesized two tris-platinum
      covalent compounds of formula (PtI2)3(sper)2 and (PtCl2)3(sper)2, one ionic
      compound of formula (sperH3)2(PtCl4)3, and another one of a covalent nature of
      formula (PtCl2sperH)2 (PtCl4) having a partially protonated spermidine residue.
      Treatment of the tris-platinum compounds with hydrogen peroxide and hydrochloric
      acid led to the production of two compounds of formula cis-trans-cis
      (PtIVCl2(OH)2)3(sper)2 and cis-(PtIVCl4)3(sper)2, respectively. All of them have
      been characterized by IR and 1H MNR spectroscopy and tested for their ability to
      interact with pUC8 plasmid DNA by the use of UV, CD, and electrophoretic
      techniques. The results suggest that all of these compounds modify the secondary
      structure of the double helix. We observed that the alteration in electrophoretic
      mobility of nicked and closed circular forms of DNA induced by the Pt(II)
      complexes is higher than that induced by the Pt(IV) complexes. The synthesized
      compounds were also assayed for antitumor activity in vitro against breast (MDA
      MB468) and leukemia (HL-60) tumor cells. Only three of these complexes may be
      regarded as potential antitumor agents, since their ID50 values are lower than 10
      micrograms/ml.

PMID- 8133255
TI  - Thiotungstate-copper interactions. I. Studies on the metabolism of [185W]
      tetrathiotungstate and the systemic interactions of labeled pharmacological doses
      with copper in rats.
AB  - [185W] tetrathiotungstate was employed to study the metabolism of thiocompounds
      in rats after i.v. injection. At tracer levels (12.5 micrograms W) the most
      important plasma binding protein eluted in the position of ceruloplasmin but the
      association did not prevent uptake of thiotungstate by the liver. At higher dose
      levels (1.5 mg W) there was considerable hydrolysis immediately after injection
      with rapid excretion of label in urine. The [185W] tetrathiotungstate remaining
      in plasma was associated with albumin and the amount retained was increased by
      pretreatment of the rats with copper. The increased binding to albumin did not
      prevent hepatic uptake and over the short-term pretreatment with copper increased
      the movement of the isotope into subcellular organelles, probably lysosomes. The
      excretion in bile was increased and the label was associated with high molecular
      weight proteins. In liver cytosol the 185W was bound by specific, as yet
      uncharacterized, proteins. At the higher dose levels there was some movement to
      higher molecular weight proteins and this was greatly increased by the
      pretreatment with copper. The studies show that the metabolism of 185W
      tetrathiotungstate is sufficiently similar to 99Mo or 35S tetrathiomolybdate for
      work on the systemic interactions of thiocompounds and copper in man and animals.

PMID- 8133256
TI  - Thiotungstate-copper interactions II. The effects of tetrathiotungstate on
      systemic copper metabolism in normal and copper-treated rats.
AB  - The intraperitoneal administration of tetrathiotungstate to rats (6-17.4 mg W/Kg
      BW) caused profound changes in copper metabolism in both normal rats and in rats
      pretreated with copper. Plasma copper associated with albumin increased, liver
      copper, particularly cytosol copper, was depleted, and biliary excretion was
      increased. There was also a movement of copper to higher molecular weight
      proteins in both liver cytosol and bile. In contrast to penicillamine,
      tetrathiotungstate did not increase liver cytosolic apometallothionein levels and
      reduced the rise provoked by copper. Metallothionein-bound copper was removed.
      Ceruloplasmin oxidase activity was inhibited and there was evidence for increased
      movement of copper into subcellular organelles, probably lysosomes. It is
      concluded that tetrathiotungstate has a genuine "decoppering" effect and could be
      considered as an alternative to thiomolybdates in the treatment of copper storage
      diseases.

PMID- 8133257
TI  - Redox properties of Desulfovibrio gigas [Fe3S4] and [Fe4S4] ferredoxins and
      heterometal cubane-type clusters formed within the [Fe3S4] core. Square wave
      voltammetric studies.
AB  - The same polypeptide chain (58 amino acids, 6 cysteines) is used to build up two
      ferredoxins in Desulfovibrio gigas a sulfate reducing organism. Ferredoxin II
      (FdII) contains a single [Fe3S4] core and ferredoxin I (FdI) mainly a [Fe4S4]
      core. The [Fe3S4] core can readily be interconverted into a [Fe4S4] complex
      (J.J.G. Moura, I. Moura, T.A. Kent, J.D. Lipscomb, B.H. Huynh, J. LeGall, A.V.
      Xavier, and E. Munck, J. Biol. Chem. 257, 6259 (1982)). This interconversion
      process suggested that the [Fe3S4] core could be used as a synthetic precursor
      for the formation of heterometal clusters. Co, Zn, Cd, and Ni derivatives were
      produced (I. Moura, J.J.G. Moura, E. Munck, V. Papaephthymiou, and J. LeGall, J.
      Am. Chem. Soc. 108, 349 (1986), K. Sureurs, E. Munck, I. Moura, J.J.G. Moura, and
      J. LeGall, J. Am. Chem. Soc. 109, 3805 (1986), and A.L. Macedo, I. Moura, J.J.G.
      Moura, K. Surerus, and E. Munck, unpublished results). The redox properties of a
      series of heterometal clusters (MFe3S4] are assessed using direct
      electrochemistry (square wave voltammetry--SWV) promoted by Mg(II) at a glassy
      carbon electrode (derivatives: Cd (-495 mV), Fe (-420 mV), Ni (-360 mV), and Co (
      245 mV) vs normal hydrogen electrode (NHE)). In parallel, the electrochemical
      behavior (cyclic voltammetry--CV, differential pulse voltammetry--DPV and SWV) of
      FdI and FdII were investigated as well as the cluster interconversion process. In
      addition to the +1/0 (3Fe cluster) and +2/+1 (4Fe cluster) redox transitions, a
      very negative redox step, at -690 mV, was detected for the 3Fe core, reminiscent
      of a postulated further 2e- reduction step, as proposed for D. africanus
      ferredoxin III by F.A. Armstrong, S.J. George, R. Cammack, E.C. Hatchikian, and
      A.J. Thomson, Biochem. J. 264, 265 (1989). The electrochemical redox potential
      values are compared with those determined by independent methods (namely by
      electron paramagnetic resonance (EPR) and visible spectroscopy).

PMID- 8133258
TI  - Regulation of parathyroid hormone-related peptide gene expression by estrogen in
      GH4C1 rat pituitary cells has the pattern of a primary response gene.
AB  - The parathyroid hormone-related peptide (PTHrP) gene has been reported to be
      subject to a wide variety of physiological and pharmacological controls. Two
      distinct patterns of PTHrP mRNA response have been recognized, one characterized
      by a prolonged or plateau response lasting many hours to days and the second
      characterized by rapid induction-deinduction kinetics and lasting 1 to several
      hours. The kinetics of the second pattern are similar to those displayed by
      primary response genes like nuclear protooncogenes, cytokines, and growth
      factors. In GH4C1 rat pituitary cells, 17 beta-estradiol induced a rapid and
      transient increase in PTHrP mRNA expression, with a peak response at 1-2 h. This
      response appeared to be due to a rapid and transient burst in gene transcription,
      which by runoff analysis was maximal at 20-40 min and declined thereafter. PTHrP
      mRNA half-life was 30 min in these cells and was unaltered by estradiol.
      Cycloheximide did not block the 17 beta-estradiol-induced response but rather
      prolonged it, and runoff analysis revealed that this effect was due to a
      prolongation or persistence of PTHrP gene transcription. These findings suggest
      that the transient nature of the native response reflects the effects of an
      estrogen-inducible repressor. All of these features are characteristic of a
      prototypical primary response gene.

PMID- 8133259
TI  - B1 and B2 bradykinin receptors encoded by distinct mRNAs.
AB  - Bradykinin receptors have been subdivided into at least two major pharmacological
      subtypes, B1 and B2. The cDNAs encoding functional B2 receptors have recently
      been cloned, but no molecular information exists at present on the B1 receptor.
      In this article, we describe experiments examining the possible relationship
      between the mRNAs encoding the B1 and B2 types of receptor. We showed previously
      that the human fibroblast cell line WI38 expresses both B1 and B2 receptors. In
      this report, we describe oocyte expression experiments showing that the B1
      receptor in WI38 human fibroblast cells is encoded by a distinct mRNA
      approximately 2 kb shorter than that encoding the B2 receptor. We have used an
      antisense approach in conjunction with the oocyte expression system to
      demonstrate that the two messages differ in sequence at several locations
      throughout the length of the B2 sequence. Taken together with the mixed
      pharmacology exhibited in some expression systems by the cloned mouse receptor,
      the data indicate that B1-type pharmacology may arise from two independent
      molecular mechanisms.

PMID- 8133260
TI  - Antisense strategy unravels a dopamine receptor distinct from the D2 subtype,
      uncoupled with adenylyl cyclase, inhibiting prolactin release from rat pituitary
      cells.
AB  - The antisense strategy was used to unravel the functional contribution of the
      mRNAs encoding dopamine (DA) receptors to the multiple transduction mechanisms
      operated by DA in rat pituitary cells. An antisense oligonucleotide was designed
      to recognize seven nucleotides upstream and 11 nucleotides downstream from the
      initiation translation codon of the mRNA that encodes the DA D2 receptor.
      Addition of the antisense oligonucleotide for 7 days to primary culture of rat
      pituitary cells resulted in a decreased expression of DA D2 receptor as shown by
      (a) the virtual disappearance of [3H]spiroperidol binding sites and (b) the
      marked reduction in the levels of both the long and the short splice variant of
      the D2 receptor mRNAs. After this treatment, the DA D2 receptor agonist
      bromocriptine lost its capability both to inhibit adenylyl cyclase activity and
      to reduce prolactin mRNA levels. On the contrary, the inhibition of prolactin
      release induced by bromocriptine was affected minimally by the antisense
      oligonucleotide treatment. These data indicate that (a) translation of the mRNA
      encoding DA D2 receptors results in receptors that are negatively coupled with
      adenylyl cyclase and functionally linked to inhibition of prolactin synthesis;
      and (b) the release of prolactin might be regulated, at least in part, by a DA
      receptor that is encoded by mRNA species distinct from those encoding the D2
      receptor.

PMID- 8133261
TI  - A rat brain cDNA encodes enzymatically active GABA transaminase and provides a
      molecular probe for GABA-catabolizing cells.
AB  - cDNAs encoding gamma-aminobutyric acid aminotransferase (GABA-T) were isolated
      from a lambda ZAP rat hippocampal cDNA expression library by two independent
      cloning methods, immunological screening with an antimouse GABA-T antibody and
      plaque hybridization with a GABA-T cDNA probe derived by polymerase chain
      reaction. We have produced enzymatically active GABA-T from a rat brain cDNA
      containing the full-length GABA-T coding region. Our rat brain GABA-T cDNAs
      hybridize to mRNAs in brain and peripheral tissues, including liver, kidney, and
      testis. We have also detected GABA-T mRNA in GABAergic cells of rat cerebellar
      cortex by in situ hybridization. Our rat brain GABA-T probe hybridizes to
      Purkinje, basket, stellate, and Golgi II cells, the same GABAergic neurons
      previously shown to contain glutamate decarboxylase GAD65 and GAD67.

PMID- 8133262
TI  - Regenerating peripheral axons transport and release low-molecular-mass materials
      in vitro.
AB  - The release of radiolabeled material from regenerating frog sciatic nerves was
      studied using a multicompartment chamber, in which the ganglia and the outgrowth
      region, respectively, were separated from the rest of the nerve. The nerves were
      incubated with radioactive amino acids in the ganglionic compartment, and the
      material transported to and released at the outgrowth region was collected and
      analyzed. Approximately 10% of the transported radioactivity was released over a
      24-h incubation period. Of the released materials, 84% had a molecular mass of <
      1,000 daltons [the low-molecular-mass (LM) fraction] as determined by exclusion
      chromatography. The presence of LM material could not be explained by leakage,
      nor was it due to intracellular or extracellular degradation of radiolabeled,
      transported proteins. It was reduced by cold and was shown by the use of
      vinblastine to be dependent on axonal transport. According to TLC, both the
      original precursor and metabolites thereof could be detected among the released
      LM material. The present results demonstrate the existence of a transport system
      for LM material in peripheral axons. The preferential release of LM over high
      molecular-mass material at the outgrowth region suggests that it could serve
      specific functions during regeneration.

PMID- 8133263
TI  - Retinoic acid-induced differentiation of human neuroblastoma SH-SY5Y cells is
      associated with changes in the abundance of G proteins.
AB  - Western blot analysis, using subtype-specific anti-G protein antibodies, revealed
      the presence of the following G protein subunits in human neuroblastoma SH-SY5Y
      cells: Gs alpha, Gi alpha 1, Gi alpha 2, Go alpha, Gz alpha, and G beta.
      Differentiation of the cells by all-trans-retinoic acid (RA) treatment (10
      mumol/L; 6 days) caused substantial alterations in the abundance of distinct G
      protein subunits. Concomitant with an enhanced expression of mu-opioid binding
      sites, the levels of the inhibitory G proteins Gi alpha 1 and Gi alpha 2 were
      found to be significantly increased. This coordinate up-regulation is accompanied
      by functional changes in mu-opioid receptor-stimulated low-Km GTPase, mu-receptor
      mediated adenylate cyclase inhibition, and receptor-independent guanosine 5'
      (beta gamma-imido)triphosphate [Gpp(NH)p; 10 nmol/L]-mediated attenuation of
      adenylate cyclase activity. In contrast, increased levels of inhibitory G
      proteins had no effect on muscarinic cholinergic receptor-mediated adenylate
      cyclase inhibition. With respect to stimulatory receptor systems, a reciprocal
      regulation was observed for prostaglandin E1 (PGE1) receptors and Gs alpha, the G
      protein subunit activating adenylate cyclase. RA treatment of SH-SY5Y cells
      increases both the number of PGE1 binding sites and PGE1-stimulated adenylate
      cyclase activity, but significantly reduced amounts of Gs alpha were found. This
      down-regulation is paralleled by a decrease in the stimulatory activity of Gs
      alpha as assessed in S49 cyc- reconstitution assays.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8133264
TI  - Intracellular calcium signals are enhanced for days after Pavlovian conditioning.
AB  - Previous observations have implicated GABA as a neurotransmitter released by the
      vestibular sensory neurons ("hair cells") of the snail Hermissenda onto visual
      sensory neurons, the type B cells, whose cell bodies are the sites of biophysical
      and biochemical changes during and following Pavlovian conditioning. Still other
      observations demonstrated that light-GABA pairings that simulate stimuli
      presented during Pavlovian conditioning cause prolonged elevation of
      intracellular Ca2+ and transformation of GABA-induced synaptic inhibition into
      excitation. Intracellular Ca2+ signals in response to GABA perfused onto the
      postsynaptic type B terminal branches are shown here to be prolonged on days
      after conditioning, but not after control paradigms. These and past results
      demonstrate two separate sites, i.e., the cell body and the terminal branches,
      for learning-induced changes after Pavlovian conditioning.

PMID- 8133265
TI  - Cholinergic deafferentation of dorsal hippocampus by fimbria-fornix lesioning
      differentially regulates subtypes (m1-m5) of muscarinic receptors.
AB  - Unilateral aspiration lesions of the rostral supracallosal stria/cingulum bundle
      and fimbria-fornix were performed on adult female rats. Ten and 24 days post
      lesioning, an elevation (17%; p < 0.01) of total muscarinic receptors was
      observed in lesioned versus control hippocampi. By using antisera selective for
      each of the five molecularly defined subtypes (m1-m5) of muscarinic receptors,
      significant changes were observed in the levels of expression for at least four
      receptor proteins. Three receptor subtypes increased in density: m1 by 14% (from
      943 to 1,078 fmol/mg); m3 by 77% (from 150 to 268 fmol/mg); and m4 by 29% (from
      220 to 285 fmol/mg). In contrast, a 22% decrease in the density of m2 receptors
      was found (from 220 to 173 fmol/mg). Detectable levels of m5 receptors were low
      in the hippocampus (approximately 1% of total receptors), and reliable
      measurements were not obtained. The directions of these changes are likely to be
      related to the pre- or postsynaptic localization of these receptor subtypes.

PMID- 8133266
TI  - Desensitization of cholecystokininB receptors in GH3 cells.
AB  - Desensitization of the cholecystokinin (CCK) octapeptide (CCK-8)-induced rise in
      intracellular free calcium concentration ([Ca2+]i) was characterized in GH3
      cells, a pituitary tumor cell line, which are known to possess CCKB receptor
      subtype. The CCK-8-induced [Ca2+]i transient was reduced following the initial
      application of CCK-8. A similar desensitization of the CCK-8-induced response was
      observed following the first application of thyrotropin-releasing hormone (TRH).
      By contrast, the TRH-induced response was not desensitized by the preceding
      application of CCK-8. Desensitization of the CCK-8-induced [Ca2+]i transient was
      associated with diminished inositol 1,4,5-trisphosphate formation. The recovery
      of desensitization of the CCK-8-induced response was delayed by a
      phosphoserine/phosphothreonine phosphatase inhibitor, calyculin A (100 nM). The
      responsiveness to CCK-8 was also reduced by phorbol 12,13-dibutyrate (PDBu), and
      this effect of PDBu was completely abolished by preincubation with staurosporine.
      Staurosporine significantly attenuated the desensitization caused by
      preincubation with CCK-8, but this effect was too small to attribute the
      desensitization to the protein kinase C transduction pathway alone. It is likely
      that desensitization of CCK receptors involves multiple transduction pathways.

PMID- 8133267
TI  - Effects of redox reagents and arsenical compounds on [3H]-cytisine binding to
      immunoisolated nicotinic acetylcholine receptors from chick brain containing
      alpha 4 beta 2 subunits.
AB  - All known nicotinic receptor alpha subunits include a conserved disulfide bond
      that is essential for function and is a site for labeling via biochemical
      modification. In an effort to develop a universal ligand for all subtypes of
      nicotinic receptors, we previously studied the effects of arsenylation with two
      compounds, p-aminophenyldichloroarsine (APA) and bromoacetyl-p
      aminophenylarsenoxide (BAPA) on nicotinic receptors from Torpedo electroplax.
      Here we apply these reagents to immunoisolated receptors containing alpha 4, beta
      2, and possibly other subunits from chick brain that bind [3H]cytisine with high
      affinity (KD approximately 5 nM). These are distinct from another receptor
      subtype that also binds [3H]cytisine and [3H]nicotine and can be arsenylated with
      APA, but instead contains alpha 5, beta 2, and probably other subunits. Reduction
      of alpha 4 beta 2 receptors with dithiothreitol blocked [3H]cytisine binding and
      this effect was reversed upon reoxidation by dithiobisnitrobenzoic acid. APA or
      BAPA prevented the dithiobisnitrobenzoic acid reactivation of dithiothreitol
      treated receptors with IC50 values of 15 and 70 nM, respectively. However, the
      antiarsenical dimercaptopropanesulfonic acid restored function to APA- or BAPA-
      "arsenylated" receptors (EC50 approximately 100 microM). APA-treated receptors
      remained blocked for up to 24 h, but treatment with dimercaptopropanesulfonic
      acid at any time restored [3H]cytisine binding. APA treatment of reduced
      receptors protected against irreversible alkylation by bromoacetylcholine,
      indicating that arsenylation occurs at least in part in the agonist binding site.
      Thus, these reagents have similar effects on different nicotinic receptor
      subtypes from both muscle and nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133268
TI  - The level of GAD67 protein is highly sensitive to small increases in
      intraneuronal gamma-aminobutyric acid levels.
AB  - Increases (> 2.5-fold) in GABA levels in rat brain lead to a large decrease in
      the level of the 67-kDa form of glutamate decarboxylase (GAD67) through a
      mechanism involving either a change in GAD67 protein stability or a change in
      GAD67 mRNA translation. In the present study, brain levels of GABA were
      manipulated by treating rats with various doses of gamma-vinyl-gamma-aminobutyric
      acid (GVG), and the dependence of total GAD activity and levels of GAD67 and
      GAD65 protein on the levels of GABA was analyzed. Initial studies showed that
      both GABA and GAD67 protein levels reached new steady-state levels after two to
      four daily injections; GABA increased 1.5- (30 mg of GVG/kg) and fourfold (150 mg
      of GVG/kg), and GAD67 protein content decreased by 30 and 70%. To assess the
      sensitivity of GAD67 to GABA, rats were injected with eight different doses of
      GVG (15-150 mg/kg) for 5 days. With increasing doses of GVG, we observed a
      gradual increase in both whole-tissue and synaptosomal GABA levels and a gradual
      decrease in GAD67 protein and GAD activity. The levels of GAD65 remained constant
      at all GVG doses. GAD67 was remarkably sensitive to GABA. The synaptosomal GAD67
      level decreased approximately 12% and the whole-neuron GAD67 level decreased
      approximately 3% for each 1% increase in nerve terminal GABA content when it was
      close to its physiological level. Our results clearly demonstrate that GAD67 is
      tightly controlled by intraneuronal GABA, and we suggest that this regulatory
      mechanism has important implications for the physiological regulation of
      GABAergic function in the mammalian brain.

PMID- 8133269
TI  - Desensitization of nicotine-stimulated [3H]dopamine release from mouse striatal
      synaptosomes.
AB  - Potential desensitization of brain nicotinic receptors was studied using a
      [3H]dopamine release assay. Nicotine-stimulated [3H]dopamine release from mouse
      striatal synaptosomes was concentration-dependent with an EC50 of 0.33 +/- 0.13
      microM and a Hill coefficient of 1.44 +/- 0.18. Desensitization by activating
      concentrations of nicotine had a similar EC50 and a half-time of 35 s.
      Concentrations of nicotine that evoked little release also induced a
      concentration-dependent desensitization (EC50 = 6.9 +/- 3.6 nM, t1/2 = 1.6-2.0
      min, nH = 1.02 +/- 0.01). Both types of desensitization produced a maximum 75%
      decrease in [3H]dopamine release. Recovery from desensitization after exposure to
      low or activating concentrations of nicotine was time-dependent with half-times
      of 6.1 min and 12.4 min, respectively. Constants determined for binding of
      [3H]nicotine to striatal membrane at 22 degrees C included a KD of 3.7 +/- 0.5
      nM, Bmax of 67.5 +/- 2.2 fmol/mg, and Hill coefficient of 1.07 +/- 0.06.
      Association of nicotine with membrane binding sites was biphasic with half-times
      of 9 s and 1.8 min. The fast rate process contributed 37% of the total reaction.
      Dissociation was a uniphasic process with a half-time of 1.6 min. Comparison of
      constants determined by the release and binding assays indicated that the [3H]
      nicotine binding site could be the presynaptic receptor involved in [3H]dopamine
      release in mouse striatal synaptosomes.

PMID- 8133270
TI  - Regional profile of developmental changes in the sensitivity of the N-methyl-D
      aspartate receptor to polyamines.
AB  - The NMDA receptor exhibits increased sensitivity to stimulation during early
      development compared with the adult. In this study, we examined modulation of the
      NMDA receptor by polyamines during development to see if it correlates with
      differences in the functional responsiveness of the NMDA receptor. [3H]MK-801
      binding was measured in discrete brain regions in the presence and absence of
      polyamines in 3-, 7-, 15-, 25-, and 60-day-old Sprague-Dawley rats. [3H]MK-801
      binding increased between postnatal days 3 and 15, with adult levels of binding
      being reached between days 15 and 25. Spermidine (75 microM) caused maximal
      stimulation of [3H]MK-801 binding during early development, ranging from 250% in
      the thalamus to 450% in the caudate putamen at postnatal day 3. This effect
      gradually declined to levels seen in the adult by postnatal days 15-25. During
      all developmental stages, the stimulation seen was greater in the caudate putamen
      compared with the hippocampus. Diethylenetriamine (1 mM) exhibited similar
      developmental and regional heterogeneity in its effects on [3H]MK-801 binding,
      producing substantial stimulation of binding in the neonate, but not in the
      adult. The EC50 and Emax values for the stimulatory effect of spermidine were
      significantly higher at day 7 compared with the adult. Unlike spermidine and
      diethylenetriamine, there was no regional variation in the effects of the
      putative "polyamine site" inverse agonist 1,10-diaminodecane at any age and only
      a slightly attenuated inhibition at postnatal day 3 compared with the
      adult.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133271
TI  - Binding of cholecystokinin-8 (CCK-8) peptide derivatives to CCKA and CCKB
      receptors.
AB  - The structural requirements for the selective binding of cholecystokinin-8 (CCK
      8)-related peptides to peripheral (CCKA) receptors are not sufficiently
      understood. In this study, the interaction of a series of newly shortened
      analogues of CCK-8 with both receptor subtypes was analyzed by displacement
      studies using [3H]-CCK-8 and 125I-Bolton-Hunter (BH)-CCK-8 as radioligands. The
      pentapeptide derivative of CCK-8, succinyl-Tyr (SO3H)-Met-Gly-Trp-Met
      phenethylamide, was found to bind selectively with high affinity to the CCKA
      receptor. The replacement of Met28 and/or Met31 by norleucine and of L-Trp30 by
      its D-analogue had no significant effect on the binding properties of the
      peptide. Further C-terminal shortening resulted in a drastic loss of affinity and
      selectivity of the CCK receptor binding.

PMID- 8133272
TI  - Characterization of the influence of unsaturated free fatty acids on brain
      GABA/benzodiazepine receptor binding in vitro.
AB  - We have investigated the effect of unsaturated free fatty acids (FFAs) on the
      brain GABA/benzodiazepine receptor chloride channel complex from mammalian,
      avian, amphibian, and fish species in vitro. Unsaturated FFAs with a carbon chain
      length between 16 and 22 carbon atoms enhanced [3H]diazepam binding in rat brain
      membrane preparations, whereas the saturated analogues had no effect. The
      enhancement of [3H]diazepam binding by oleic acid was independent of the
      incubation temperature (0-30 degrees C) of the binding assay and not additive to
      the enhancement by high concentrations of Cl-. In rat brain preparations, the
      stimulation of [3H]diazepam binding by oleic acid (10(-4) M) was independent of
      the ontogenetic development. Phylogenetically, large differences were found in
      the effect of unsaturated FFAs on [3H]diazepam and [3H]muscimol binding: In
      mammals and amphibians, unsaturated FFAs enhanced both [3H]-muscimol and
      [3H]diazepam binding to 150-250% of control binding. In 17 fish species studied,
      oleic acid (10(-4) M) stimulation of [3H]diazepam binding was weak (11 species),
      absent (four species), or reversed to inhibition (two species), whereas
      stimulation of [3H]muscimol binding was of the same magnitude as in mammals and
      amphibians. In 10 bird species studied, only weak enhancement of [3H]muscimol
      binding (110-130% of control) by oleic acid (10(-4) M) was found, whereas
      [3H]diazepam binding enhancement was similar to values in mammal species.
      Radiation inactivation of the receptor complex in situ from frozen rat cortex
      showed that the functional target size for oleic acid to stimulate
      [3H]flunitrazepam binding has a molecular mass of approximately 200,000
      daltons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133273
TI  - Endothelin- and sarafotoxin-induced phosphoinositide hydrolysis in cultured
      canine tracheal smooth muscle cells.
AB  - The endothelins (ETs) and sarafotoxin are two structurally related classes of
      potently contractile peptides. To understand the mechanism of action of ETs, we
      have examined the effect of ETs and sarafotoxin on phosphoinositide (PI)
      hydrolysis in cultured canine tracheal smooth muscle cells (TSMCs). ET-1, ET-2,
      ET-3, and sarafotoxin caused dose-dependent accumulation of inositol phosphatase
      (IPs) and tracheal smooth muscle contraction. BQ-123, an ETA receptor antagonist,
      had a high affinity to block the ET-1-induced IP accumulation and tracheal smooth
      muscle contraction with pKB values of 7.3 and 7.4, respectively. Pretreatment of
      TSMCs with cholera toxin impaired the ability of ET-1 and ET-2 to stimulate IP
      formation, whereas there was no effect by treatment with pertussis toxin.
      Stimulation of PI turnover by these peptides required the presence of
      extracellular Ca2+ and was blocked by treatment with EGTA. The addition of Ca2+
      (3-620 nM) to digitonin-permeabilized TSMCs directly stimulated IP accumulation.
      A further Ca(2+)-dependent increase in IP formation was obtained by inclusion of
      either GTPrS or ET-1. The combined presence of GTPrS and ET-1 elicited an
      additive effect on IP formation. Short-term exposure to phorbol 12-myristate 13
      acetate (PMA, 1 microM) abolished the stimulation of PI hydrolysis induced by
      these peptides. The inhibitory effect of PMA on ET-induced response was reversed
      by staurosporine, a protein kinase C (PKC) inhibitor, suggesting that the
      inhibitory effect of PMA is mediated through the activation of PKC. Prolonged
      incubation of TSMCs with PMA resulted in a recovery of receptor responsiveness
      that may be due to downregulation of PKC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133274
TI  - Stereoselectivity of the inhibition of [3H]hemicholinium-3 binding to the sodium
      dependent high-affinity choline transporter by the enantiomers of alpha- and beta
      methylcholine.
AB  - In a previous report, we showed that the enantiomers of alpha- and beta
      methylcholine inhibited choline uptake with stereoselectivity, but that their
      transport by the choline carrier of nerve terminals showed stereospecificity. The
      present experiments used the same choline analogues to determine if either of the
      above characteristics pertains to their ability to interact with the [3H]
      hemicholinium-3 binding site present on striatal membranes and synaptosomes.
      [3H]Hemicholinium-3 binding to striatal membranes could be inhibited
      stereoselectively by the enantiomers of beta-methylcholine, but R(+)-alpha
      methylcholine was little better than its enantiomer in this test. However,
      [3H]hemicholinium-3 binding to striatal synaptosomes was inhibited
      stereoselectively by the enantiomers of both alpha- and beta-methylcholine. This
      difference between the properties of [3H]hemicholinium-3 binding to membranes or
      to synaptosomes appears related to the presence of two ligand binding states. The
      [3H]hemicholinium-3 binding site could be shifted to a low-affinity state by ATP
      treatment and to a high-affinity state by EDTA washing. When the
      [3H]hemicholinium-3 binding site existed in its low-affinity state, binding was
      inhibited stereoselectively by the enantiomers of both alpha- and beta
      methylcholine, but when shifted to its high-affinity state, it was inhibited
      stereoselectively only by the enantiomers of beta-methylcholine. We conclude that
      hemicholinium-3 interacts with the substrate recognition site of the high
      affinity choline transporter, but that the stereoselectivity of this site changes
      depending on its affinity state.

PMID- 8133275
TI  - Synthesis of specific proteins in trophic factor-deprived neurons undergoing
      apoptosis.
AB  - Apoptosis, also known as programmed cell death, is a mechanism used by different
      tissues to regulate their cell content. In the nervous system, this process is
      supposed to adjust the final number of neurons to the number of the target cells
      they are innervating. The demonstration that, in several systems in vitro and in
      vivo, neuronal apoptosis can be prevented by inhibiting RNA or protein synthesis
      suggests that an activation of gene expression is required in the cells that are
      going to die. The genes involved and their products, named "killer proteins," are
      not known in the superior vertebrates. In order to identify such proteins, we
      have used and characterized an in vitro model consisting of neurons derived from
      8-day-old embryonic chicken ciliary ganglia. RNA and protein synthesis inhibitors
      can prevent the death of these neurons when they are deprived of trophic support.
      Comparing the synthesis of proteins in trophic-supported neurons with that in
      trophic-deprived neurons by the use of two-dimensional polyacrylamide gel
      electrophoresis, we have observed that several proteins were overexpressed
      reproducibly in the apoptotic cells. We found that all these proteins are
      localized in the nucleus, suggesting that they may be transcription regulators.

PMID- 8133276
TI  - Increased GABA release in the human brain cortex as a potential pathogenetic
      basis of hyperosmolar diabetic coma.
AB  - Human cerebral cortical slices preincubated with [3H]GABA, [3H]noradrenaline, or
      5-[3H]hydroxytryptamine and superfused with Krebs solution or Mg(2+)-free Krebs
      solution were used to investigate the influence of increased D-glucose
      concentrations on the release of these [3H]-neurotransmitters evoked by high K+
      content or NMDA receptor activation, respectively. An increase in level of D
      glucose (normal content, 11.1 mM) by 32, 60, and/or 100 mM (a range
      characteristic for hyperosmolar diabetic coma) increased the [3H]GABA release and
      inhibited the [3H]noradrenaline release evoked by both methods of stimulation.
      The K(+)-induced 5-[3H]hydroxytryptamine release was also inhibited by high D
      glucose content. Blockade of GABAB receptors by p-(3-aminopropyl)-p
      diethoxymethylphosphinic acid (CGP 35348) attenuated the inhibitory effect of
      high D-glucose content on the K(+)-evoked release of [3H]noradrenaline and 5
      [3H]hydroxytryptamine, suggesting that the effect on monoamine release is, at
      least to a major part, the result of the increased GABA release and, as a
      consequence, of an increased GABA concentration at inhibitory GABAB receptors.
      The membrane-impermeable sorbitol mimicked the increasing effect of D-glucose on
      [3H]GABA release and its inhibitory effect on 5-[3H]hydroxytryptamine release.
      However, dimethyl sulfoxide, which is known to permeate rapidly through
      biological membranes, had no effect at concentrations equiosmolar to D-glucose.
      It is concluded that a reduction in brain cell volume caused by increased
      extracellular, compared with cytoplasmic, osmolarity is crucial for the changes
      in neuronal function observed at high D-glucose and sorbitol content.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8133277
TI  - Identification of endothelin receptor subtype (ETB) in human cerebral cortex
      using subtype-selective ligands.
AB  - Specific endothelin (ET) binding sites were characterized in membranes prepared
      from human cerebral cortices using binding assay and cross-linking analysis. The
      presence of immunoreactive (IR) ET-1 was studied by radioimmunoassay. Saturation
      binding experiments revealed that the KD and Bmax for 125I-ET-1 and 125I-ET-3 to
      membranes from gray matter were 25 +/- 6 pM and 115 +/- 15 fmol/mg of protein and
      24 +/- 5 pM and 108 +/- 13 fmol/mg of protein, respectively. Similar results were
      obtained for white matter. In the presence of 10 nM sarafotoxin-6c, which is
      selective for ETB receptors, 125I-ET-1 and 125I-ET-3 binding was totally
      abolished. However, in the presence of 1 microM BQ123, which is selective for ETA
      receptors, both bindings were not affected. These results suggest that the human
      cerebral cortex contains only ETB receptors. Cross-linking of 125I-ET-1 and 125I
      ET-3 to membranes with disuccinimidyl suberate resulted in the labeling of two
      bands of 48 and 31 kDa. Concentrations of IR-ET-1 in the gray and white matter
      were 7.0 +/- 3.2 and 2.5 +/- 1.7 fmol/g wet weight, respectively. The
      demonstration of high-affinity ETB receptors and the presence of IR-ET-1 suggest
      that the peptide may act as a neurotransmitter or neuromodulator in the human
      cerebral cortex.

PMID- 8133278
TI  - Differential cytotoxicities of N-methyl-beta-carbolinium analogues of MPP+ in
      PC12 cells: insights into potential neurotoxicants in Parkinson's disease.
AB  - N-Methylated beta-carbolinium cations that can form in vivo from environmental or
      endogenous beta-carbolines are putative neurotoxic factors in Parkinson's
      disease. The cytotoxicities of 11 N-methylated beta-carbolinium cations and N
      methyl-4-phenylpyridinium cation (MPP+), the experimental parkinsonian
      neurotoxicant which the carbolinium cations structurally resemble, were examined
      using rat pheochromocytoma (PC12) cells cultured in "low energy" N-5 medium; cell
      death was estimated by released lactate dehydrogenase activity and viable cell
      protein. Of the eight N2-monomethylated beta-carbolinium cations utilized, only 2
      methyl-harmalinium (harmaline-2-methiodide) was as cytotoxic as MPP+. Also, three
      N2(beta), N9(indole)-dimethylated beta-carbolinium cations displayed cytotoxic
      effects, with the simplest, 2,9-dimethylnorharmanium, approaching the
      effectiveness of MPP+ in PC12 cells cultured in N-5 medium. However, when PC12
      cells grown in higher energy Dulbecco's modified Eagle's medium were utilized
      with selected effective cations, it was observed that the cultures were
      relatively resistant to MPP+ and 2,9-dimethylnorharmanium, but remained
      vulnerable to 2-methylharmalinium. The results are interpreted to mean that
      different cytotoxic mechanisms exist for the two most potent beta-carbolinium
      cations--namely, a mechanism for the 2,9-dimethyl-beta-carbolinium species that,
      as with MPP+, is conditional on mitochondrial ATP depletion, but a different (or
      additional) mechanism for 2-methylharmalinium that is independent of
      mitochondrial inhibition. The possible accumulation of these cytotoxic cations in
      Parkinson's disease is discussed in the context of these findings.

PMID- 8133279
TI  - Functional, metabolic, and circulatory changes associated with seizure activity
      in the postischemic brain.
AB  - The present study was undertaken to explore how transient ischemia in rats alters
      cerebral metabolic capacity and how postischemic metabolism and blood flow are
      coupled during intense activation. After 6 h of recovery following transient
      forebrain ischemia 15 min in duration, bicuculline seizures were induced, and
      brains were frozen in situ after 0.5 or 5 min of seizure discharge. At these
      times, levels of labile tissue metabolites were measured, whereas the cerebral
      metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) were measured
      after 5 min of seizure activity. After 6 h of recovery, and before seizures,
      animals had a 40-50% reduction in CMRO2 and CBF. However, because CMRO2 rose
      three-fold and CBF fivefold during seizures, CMRO2 and CBF during seizures were
      similar in control and postischemic rats. Changes in labile metabolites due to
      the preceding ischemia encompassed an increased phosphocreatine/creatine ratio,
      as well as raised glucose and glycogen concentrations. Seizures gave rise to
      minimal metabolic perturbation, essentially comprising reduced glucose and
      glycogen contents and raised lactate concentrations. It is concluded that
      although transient ischemia leads to metabolic depression and a fall in CBF, the
      metabolic capacity of the tissue is retained, and drug-induced seizures lead to a
      coupled rise in metabolic rate and blood flow.

PMID- 8133280
TI  - Evidence for the involvement of carnitine-dependent long-chain acyltransferases
      in neuronal triglyceride and phospholipid fatty acid turnover.
AB  - This study focuses on the potential involvement of carnitine palmitoyltransferase
      (CPT) on the phospholipid and triglyceride fatty acid turnover in neurons. This
      category of enzymes, which has been identified in several rat brain tissues, is
      well known for its role in modulating cellular fatty acid oxidation. Neuronal
      cell cultures from rat brain cortex incorporated radioactive palmitate or oleate
      into phospholipids and triglycerides. The largest fraction of radioactive fatty
      acids was recovered in phosphatidylcholine followed by triglycerides and, to a
      lesser extent, phosphatidylethanolamine. CPT activity measured in neuronal
      lysates obtained from neurons treated with 40 microM 2-tetradecylglycidic acid
      (TDGA) was almost completely abolished. Furthermore, between 2 and 10 microM TDGA
      CPT activity dropped more rapidly than between 10 and 40 microM. When the cells
      were pretreated with TDGA, the incorporation process of either radioactive fatty
      acid into triglycerides was dose-dependently suppressed. Radioactive fatty acid
      incorporation into phosphatidylcholine was significantly decreased in cells
      treated with TDGA. In contrast, phosphatidylethanolamine reacylation was
      essentially not affected by the CPT inhibitor. Similar results on the fatty acid
      incorporation into triglycerides and phospholipids were observed with neurons
      treated with palmitoyl-DL-aminocarnitine (PAC), a reversible CPT inhibitor, which
      does not consume free CoA. These effects do not seem to be the result of an
      inhibitory activity toward one of the steps involved in the acylation-deacylation
      process of triglycerides or phospholipids, as cellular lysates from TDGA-treated
      cells or lysates containing PAC incorporated radioactive fatty acids at rates
      comparable to controls. Our results suggest that CPT may be an important partner
      in the pathway of phospholipid and triglyceride fatty acid turnover in neurons.

PMID- 8133281
TI  - Isoprenylated proteins in myelin.
AB  - Incubation of rat brainstem slices with [3H]-mevalonate ([3H]MVA) in the presence
      of lovastatin resulted in the incorporation of label into three groups of myelin
      associated proteins with molecular masses of 47, 21-27, and 8 kDa, as revealed on
      sodium dodecyl sulfate-polyacrylamide rod gel electrophoresis. Although the gel
      patterns of [3H]MVA-derived prenylated proteins were similar, the relative level
      of 3H incorporated into each protein species differed between myelin and the
      brainstem homogenate. Immunoprecipitation studies identified the 47-kDa
      prenylated protein as a 2'-3'-cyclic nucleotide phosphodiesterase, whereas the 8
      kDa protein proved to be the gamma subunit of membrane-associated guanine
      nucleotide regulatory protein. The 3H-labeled 21-27-kDa group in myelin
      corresponds to the molecular mass of the extensive Ras-like family of monomeric
      GTP-binding proteins known to be prenylated in other tissues. Increase in
      lovastatin concentration resulted in reduced levels of [3H]MVA-labeled species in
      myelin and concomitantly increased levels in the cytosol. A cold MVA chase
      restored to normality the appearance of [3H]MVA-labeled proteins in myelin.
      Furthermore, a high lovastatin concentration in the brainstem slice incubation
      mixture altered the appearance of newly synthesized nonprenylated myelin
      proteins, including proteolipid protein and the 17-kDa subspecies of myelin basic
      protein. Because other myelin proteins were unaffected by the high lovastatin
      concentration, restricting the availability of MVA in myelin-forming cells may
      selectively alter processes required for myelinogenesis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8133282
TI  - In vitro activation of rat brain protein kinase C by polyenoic very-long-chain
      fatty acids.
AB  - A variety of fatty acids including the cis-polyunsaturated very-long-chain fatty
      acids (VLCFA) (> 22 carbon atoms) common in retina, spermatozoa, and brain were
      examined for their ability to activate protein kinase C (PKC) purified from rat
      brain. Arachidonic [20:4(n-6)], eicosapentaenoic [20:5(n-3)], and docosahexaenoic
      [22:6(n-3)] acids as well as the VLCFA dotriacontatetraenoic [32:4(n-6)] and
      tetratriacontahexaenoic [34:6(n-3)] were equally capable of activating PKC in
      vitro with maximal activity being between 25 and 50 microM. The phorbol ester 12
      O-tetradecanoylphorbol 13-acetate further enhanced the in vitro activation of PKC
      when added to the protein kinase assay system with the fatty acids. The fully
      saturated arachidic acid (20:0) was inactive in both assay systems. The potential
      significance of the in vitro activation of PKC by the VLCFA is discussed.

PMID- 8133283
TI  - Differential activities of protein phosphatase types 1 and 2A in cytosolic and
      particulate fractions from rat forebrain.
AB  - The activities and concentrations of protein phosphatase type 1 (PP1) and type 2A
      (PP2A) were compared in cytosol and particulate fractions of rat forebrain.
      Although the activity of PP2A was highest in the cytosol, immunoblot analysis
      with a PP2A-specific antibody showed that there were significant levels of the
      enzyme in the particulate fraction. There was no significant difference between
      the concentration of PP2A in the cytosol and particulate fractions such that the
      low activity of PP2A in the particulate fraction represents an inactivation of
      this form of the enzyme. Similar analysis in skeletal muscle, heart, and liver
      showed this finding was unique to the brain. Similarly, the majority of PP1
      activity was recovered in the cytosol, but most PP1 enzyme was associated with
      the particulate fraction. Comparison with other tissues showed that the
      activities of PP1 in the particulate fractions were similar but that the
      forebrain contained significantly more enzyme than the other tissues. Thus, like
      PP2A it appears that the specific activity of PP1 in the particulate fraction of
      rat forebrain is much lower than that of the cytosol and of the particulate
      fractions of other tissues. Elution of PP1 and PP2A from membranes with 0.5 M
      NaCl plus 0.3% Triton X-100 resulted in severalfold activation of both enzymes.
      That the majority of PP1 and PP2A in rat forebrain are associated with membrane
      structures but in a low activity state suggests that novel regulatory mechanisms
      exist that have considerable and unique potential for activation of protein
      dephosphorylation.

PMID- 8133284
TI  - Effect of fish oil diet on fatty acid composition of phospholipids of brain
      membranes and on kinetic properties of Na+,K(+)-ATPase isoenzymes of weaned and
      adult rats.
AB  - The influence of dietary (n-3) fatty acids (such as eicosapentaenoic and
      docosahexaenoic acids) as found in fish oil on Na+ sensitivity and ouabain
      affinity of Na+,K(+)-ATPase isoenzymes (alpha 1, alpha 2, alpha 3) was studied in
      whole brain membranes from weaned and adult rats fed diets for two generations.
      The long chain (n-3) fatty acids supplied by fish oil decreased the fatty acids
      of the (n-6) series compared with the standard diet, resulting in a decrease in
      the (n-6)/(n-3) molar ratio in both 21- and 60-day-old rats. On the basis of
      ouabain titration, three inhibitory processes with markedly different affinities
      were associated with isoenzymes, i.e., low affinity (alpha 1), high affinity
      (alpha 2), and very high affinity (alpha 3). It appears that the fish oil diet,
      in part via the modification of membrane fatty acid composition, altered the
      proportion and ouabain affinity of isoenzymes. Na+ sensitivity is the best
      criterion of physiologic change induced by fish oil diet. We calculated the Na+
      activation for each isoenzyme and found one Na+ sensitivity and two Na+
      sensitivities per isoenzyme in weanling and adult rats fed different diets,
      respectively. In contrast to alpha 2 and alpha 3, alpha 1 appears insensitive to
      membrane change induced by fish oil diet. Fish oil diet, which is known to confer
      cardioprotection, induced significant modulation of Na+,K(+)-ATPase isoenzymes at
      the brain level.

PMID- 8133285
TI  - Use of ELISA to G4 antigen to quantitate neurite outgrowth in the chick both in
      vivo and in vitro.
AB  - The G4 glycoprotein is found on the earliest developing neurite tracts of the
      chick embryo. An ELISA is introduced here to quantify the amount of G4-expressing
      neurites in the picogram range. In this double-sandwich assay, an anti-G4
      monoclonal antibody fixes the G4 antigen to the plastic surface, which then is
      detected by a polyclonal antiserum; nonspecific background is decreased by
      competitive displacement. The sensitivity of the assay allows us to follow
      quantitatively the very first neurite growth in embryonic heads, trunks, retinae,
      and brains. G4-based neurite growth is shown to occur earlier in heads than in
      trunks; in brain it is nearly 10-fold higher than in the retina by embryonic day
      8. By determination of acetylcholinesterase (AChE) activities from the same
      homogenates, our earlier histochemical findings are verified now on a
      quantitative basis, again showing that AChE consistently precedes G4 antigen.
      Moreover, as an in vitro example, the G4 ELISA is applied to the nerve growth
      factor (NGF) standard bioassay on dorsal root ganglia; the half-maximal response
      is reached at approximately 10 ng/ml of NGF for G4-based neurite growth and at
      approximately 1 ng/ml of NGF for AChE expression, respectively.

PMID- 8133286
TI  - Monogalactosyl diglyceride, a marker for myelination, activates oligodendroglial
      protein kinase C.
AB  - Protein kinase C (PKC) is activated by 1,2-sn-diacylglycerol (DAG), the source of
      which can either be phosphatidylinositol bisphosphate or phosphatidylcholine.
      Here, we show that monogalactosyl diglyceride (MGDG), a minor galactolipid
      present in oligodendrocytes (OLs) and myelin, which is designated as a marker for
      myelination, can enhance OL PKC activity. Based on different calcium and
      substrate requirements we conclude that MGDG and DAG activate different isoforms
      of PKC group A: MGDG primarily stimulates PKC-alpha, and DAG primarily activates
      PKC-gamma. The presence of these PKC isoforms in OLs was confirmed by western
      blotting, whereas PKC-beta was only weakly stained, if at all. Addition of MGDG
      to the culture medium provided a higher density of regenerating OL fibers, which
      was not observed when membrane-permeable DAG was used. These findings indicate
      that MGDG can modulate the OL PKC activity and that PKC-alpha is the major PKC
      isoform involved in OL process formation.

PMID- 8133287
TI  - Production and characterization of a new specific antiserum against the taurine
      putative biosynthetic enzyme cysteine sulfinate decarboxylase.
AB  - We have shown previously that cysteine sulfinate decarboxylase (CSD), the
      putative biosynthetic enzyme of taurine in the brain, is identical to the liver
      enzyme according to biochemical, kinetic, and immunochemical criteria. In the
      present work, CSD was purified in its native form from rat liver. The
      purification was performed in eight steps, which included conventional
      chromatography (diethylaminoethyl cellulose, hydroxylapatite), followed by HPLC
      (hydrophobic, adsorption, and ion-exchange HPLC). The purification factor was
      11,000, and the final yield was around 2%. The procedure led to the enrichment of
      a protein, the molecular mass of which was 51,000 daltons as determined by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The final fraction was more
      than 90% homogeneous. By using this fraction as the antigen, an antiserum was
      raised in rabbit that (a) quantitatively immunoprecipitated CSD activity from
      liver and brain extract, and (b) immunolabeled one band (51,000 daltons) on
      immunoblots of partially purified fractions from liver. Enrichment of CSD
      specific activity and that of the protein immunolabeled by the antiserum for a
      given step, e.g., hydrophobic HPLC, were consistently parallel. The antiserum was
      used to carry out CSD immunocytochemistry in cerebellum. Numerous small cells
      were labeled in the Purkinje cell layer, the granular layer, and the white
      matter. In the molecular layer, Bergmann radial fibers were immunostained. The
      Purkinje and stellate cells were devoid of any labeling at the cell body and
      terminal levels. The antiserum appears to be specific for CSD and suitable for
      immunocytochemical visualization of CSD in the brain.

PMID- 8133288
TI  - Somataglycan-S: a neuronal surface proteoglycan defines the spinocerebellar
      system.
AB  - The formation and maintenance of functionally specific neuronal networks may
      depend on specific proteoglycans localized to the surface membranes of a subset
      of neurons. Monoclonal antibody (MAb) 6A2 labeled a distinct subset of CNS
      neurons: the somas and proximal dendrites of cells making up the spinocerebellar
      and reticular systems. These pathways contribute to proprioceptive and
      exteroceptive functions. Ultrastructurally, MAb 6A2 immunoreactivity was
      distributed focally along the cell surface membranes and the adjacent
      extracellular space. On western blots of immunoaffinity-purified preparations
      from cerebellar homogenates, a major, broad band of approximately 400 kDa is
      labeled by MAb 6A2. Increased electrophoretic mobility of the purified antigen
      after digestion with chondroitinase ABC and keratanase suggests that the antigen
      is a proteoglycan bearing chondroitin sulfate and keratan sulfate
      glycosaminoglycans. Unsulfated N-acetyl-galactosamine residues linked to
      unsaturated uronic acid constituted the initial disaccharide in the chondroitin
      sulfate glycosaminoglycan chains. N- and O-linked oligosaccharides on the core
      protein were detected by the biotinylated lectins wheat germ agglutinin and
      Jacalin, respectively, and by MAb anti-HNK-1. Lyase and glycosidase digests
      result in a 280-kDa band. This proteoglycan, somataglycan-S, may provide a key to
      the role of glycoconjugates in determining neuronal diversity and system
      specificity.

PMID- 8133289
TI  - Muscle mitochondrial ATP production in progressive supranuclear palsy.
AB  - Six patients with progressive supranuclear palsy (PSP) and 12 age-matched disease
      free subjects participated in this study designed to compare rates of ATP
      production by intact mitochondria from biopsied skeletal muscle. When pyruvate
      and malate were used as metabolic substrates, rates of ATP production were 0.184
      +/- 0.025 mumol/min/U of citrate synthase (CS) activity (a mitochondrial marker)
      in control subjects and 0.131 +/- 0.051 mumol/min/U of CS in PSP patients. In the
      presence of succinate, rates of ATP formation were 0.137 +/- 0.02 mumol/min/U of
      CS in controls and 0.109 +/- 0.04 mumol/min/U of CS in patients. With N,N,N',N'
      tetramethyl-p-phenylenediamine (TMPD) and ascorbate, rates were 0.034 +/- 0.008
      mumol/min/U of CS in controls and 0.022 +/- 0.01 mumol/min/U of CS in PSP
      subjects. Differences between the control and PSP populations reached statistical
      significance with pyruvate/malate and TMPD/ascorbate. No differences in either
      muscle histopathology or histochemistry were found between patient and control
      subjects. Results of this study suggest that oxidative phosphorylation defects
      occur in muscle mitochondria from patients with PSP.

PMID- 8133290
TI  - Chronic ingestion of ethanol up-regulates NMDAR1 receptor subunit
      immunoreactivity in rat hippocampus.
AB  - We examined the effects of chronic ethanol exposure on the levels of N-methyl-D
      aspartate receptor subunit 1 (NMDAR1) protein, an essential component of N-methyl
      D-aspartate glutamate receptors, in rat brain. By immunoblotting procedures using
      a specific antibody for the NMDAR1 subunit, we found that ethanol dramatically up
      regulated (by 65%) NMDAR1 immunoreactivity in the hippocampus but not in the
      nucleus accumbens, cerebral cortex, or striatum. In contrast, ethanol did not
      alter the levels of glutamate receptor subunit (GLUR) 1 or GLUR2 protein,
      subunits that make up the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid glutamate receptor, in the hippocampus. Because ethanol can potentially
      influence many different neurotransmitter systems, we examined whether chronic
      treatment with several psychotropic drugs with different pharmacological profiles
      (cocaine, haloperidol, SCH 23390, imipramine, and morphine) could mimic the
      effect of ethanol. None of these agents increased hippocampal NMDAR1 subunit
      immunoreactivity after chronic administration. Increased NMDAR1 subunit levels in
      the hippocampus after chronic ethanol exposure may represent an important
      neurochemical substrate for some of the features associated with ethanol
      dependence and withdrawal.

PMID- 8133291
TI  - Activation of protein kinase C inhibits kainate-induced currents in oocytes
      expressing glutamate receptor subunits.
AB  - The effect of protein kinase C (PKC) activation on maximal kainate (KA)-induced
      currents was studied in Xenopus oocytes expressing the glutamate receptor (GluR)
      subunits GluR3, GluR1 + 3, GluR2 + 3, and GluR6. The PKC activator phorbol 12
      myristate 13-acetate (PMA) inhibited peak KA responses in a time-dependent
      manner. The magnitude of inhibition was greatest in GluR6-expressing oocytes.
      Desensitizing KA currents characterized by a peak, transient current followed by
      a slower, desensitizing current were observed in oocytes expressing GluR3 and
      GluR1 + 3 receptors. PMA inhibited the desensitization, and this effect could be
      observed before PMA's inhibition of peak current amplitude. PMA-mediated
      inhibition of both desensitization and peak current amplitude was prevented by
      intracellular injection of the protein kinase C (PKC) inhibitor peptide. These
      results suggest that the function of GluRs is regulated by PKC-dependent
      phosphorylation.

PMID- 8133292
TI  - Isolation and characterization of the promoter of the human GABAA receptor alpha
      1 subunit gene.
AB  - The GABAA receptor, as assessed by ligand binding and chloride flux measurement
      in vivo and in vitro, is down-regulated in response to chronic benzodiazepine
      exposure. The mRNA levels of the alpha 1 and gamma 2 subunits of the receptor are
      also reduced. We have isolated the promoter of the gene encoding the alpha 1
      subunit of the GABAA receptor to elucidate the regulatory mechanism of its
      expression. A DNA segment 650 bp long has been isolated that includes 151 bp of
      untranslated 5' end of the cDNA sequence and 500 bp of potential promoter
      enhancer region. The transcriptional activity of this DNA segment linked to the
      firefly luciferase gene showed a strong orientation specificity. The promoter
      activity was localized to a 60-bp segment by deletion mapping. Mobility shift
      binding assay results suggest that this segment may interact with one or more
      factors in HeLa cell nuclear extracts to form a transcriptional complex. Primary
      cultures of embryonic chick cortical cells transfected with the promoter
      luciferase construct were treated chronically with lorazepam. Transcriptional
      activity of this promoter construct was strongly repressed by chronic
      administration of lorazepam.

PMID- 8133293
TI  - New structures and bioactivity patterns of bengazole alkaloids from a choristid
      marine sponge.
AB  - New bengazoles 3-9 as inseparable mixtures are reported from the sponge Jaspis
      cf. coricea collected in Papua New Guinea. These compounds contain a new
      variation of the unusual bisoxazole core present in bengazole A [1]. The B-ring
      oxazole hexatetraol side chain is varyingly substituted with either myristic acid
      or 13-methylmyristic acid. Hydrolysis of three different bengazole mixtures each
      yielded an identical tetraol, bengazole Z [11].

PMID- 8133294
TI  - Two new sesquiterpene lactones from Ceiba pentandra.
AB  - Two new sesquiterpene lactones showing moderate antimicrobial activity have been
      isolated from the root bark of Ceiba pentandra (Bombacaceae) in addition to the
      known compounds 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4
      naphthaquinone+  ++ [1], and 7-hydroxycadalene [2]. The new compounds were
      characterized as 2,7-dimethoxy-5-isopropyl-3-methyl-8,1-naphthalene carbolactone
      [3] and 2-hydroxy-5-isopropyl-7-methoxy-3-methyl-8,1-naphthalene carbolactone [4]
      by chemical and spectroscopic studies.

PMID- 8133295
TI  - Trehalose esters from the aspen fungus Hyphozyma lignicola.
AB  - Chemical investigation of the metabolites produced when a new fungus, Hyphozyma
      lignicola, isolated from blackgalls on aspen, was grown in malt extract liquid
      medium resulted in the isolation and identification of five trehalose esters 1-5,
      which are unusual fungal metabolites. The major compound is 3,6-di-O-acetyl-2-O
      octadecanoyl-alpha,alpha-D-trehalose [2]. The structures were established by the
      analysis of nmr and fabms data in combination with chemical degradation.

PMID- 8133296
TI  - Cannabis, 21. Biotransformation of cannabinol to its glycosides by in vitro plant
      tissue.
AB  - A marijuana compound, cannabinol [1], was converted to two metabolites using in
      vitro tissue of Pinellia ternata. The structures of the metabolites were
      determined to be cannabinol-O-beta-D-glucopyranoside [2] and 9'-hydroxycannabinol
      O-beta-D-glucopyranoside [3] by 1H nmr and 13C nmr. From the time course
      experiments, 1 was absorbed rapidly in the tissues and glycosylated.
      Hydroxylation at the pentyl group occurred, and its metabolite was secreted in
      the medium.

PMID- 8133297
TI  - Antitumor agents, 145. Cytotoxic asprellic acids A and C and asprellic acid B.
      new p-coumaroyl triterpenes, from Ilex asprella.
AB  - Three new p-coumaroyl triterpenes, asprellic acids A [1], B [2], and C [3], were
      isolated from the EtOH extract of dried leaves of Ilex asprella. The structures
      for 1-3 have been established as 3,27-di-O-trans-p-coumaroyl [1], 3-O-trans-p
      coumaroyl-27-O-cis-p-coumaroyl- [2], and 3-O-cis-p-coumaroyl-27-O-trans-p
      coumaroyl- [3] 3 beta,27-dihydroxyolean-12-en-28-oic acid, respectively, by
      spectral and chemical examinations. Asprellic acid A [1] exhibited potent
      cytotoxicity against the RPMI-7951 cell line with an ED50 value of 0.62
      micrograms/ml, while the cytotoxicity of asprellic acid C [3] against RPMI-7951
      was marginal (ED50 5.5 micrograms/ml). Compounds 1 and 3 also showed cytotoxicity
      against KB cells with ED50 values of 3.75 and 2.86 micrograms/ml, respectively.
      Asprellic acid B [2] did not show cytotoxicity (> 10 micrograms/ml) against KB or
      RPMI-7951 cell lines.

PMID- 8133298
TI  - Novel antimitotic dibenzocyclo-octadiene lignan constituents of the stem bark of
      Steganotaenia araliacea.
AB  - By means of activity-directed chromatographic fractionation using cultured
      astrocytoma (ASK) cells, six dibenzocyclo-octadiene lignans were isolated from
      Steganotaenia araliacea stem bark. In addition to the most abundant analogue,
      steganangin [1], two other known compounds, steganacin [3] and steganolide A [6],
      and three new compounds, episteganangin [2], steganoate A [4], and steganoate B
      [5], were obtained. Episteganangin [2] was chemically correlated with the known
      ketone steganone [7]. All of these compounds demonstrated cytotoxic activity when
      tested against a panel of eleven human tumor cell lines, with the exception of
      steganoate A [4]. The magnitude of this activity tended to correlate with
      antimitotic activity observed with the ASK assay and in vitro inhibition of
      microtubule assembly. Steganacin [3] was less cytotoxic than colchicine, but more
      active in these latter two assay systems.

PMID- 8133299
TI  - Bruceanols D, E, and F three new cytotoxic quassinoids from Brucea
      antidysenterica.
AB  - Three new quassinoids, bruceanols D [1], E [2], and F [3], were isolated from
      Brucea antidysenterica, and their structures were elucidated by spectral evidence
      and chemical transformation. All of these compounds exhibited cytotoxicity
      against five human tumor cell lines, malignant melanoma (RPMI-7951), lung
      carcinoma (A-549), ileocecal adenocarcinoma (HCT-8), epidermoid carcinoma of the
      nasopharynx (KB), and medulloblastoma (TE-671), and against murine lymphocytic
      leukemia (P-388).

PMID- 8133300
TI  - Starfish saponins, 52. Chemical constituents from the starfish Echinaster
      brasiliensis.
AB  - This paper reports an analysis of the chemical constituents from the Caribbean
      starfish Echinaster brasiliensis collected at Grand Bahama Island. This species
      is completely devoid of cyclic steroidal glycosides, previously isolated from two
      species of the genus Echinaster in place of the more common penta- and hexa
      glycoside steroidal sulfates ("asterosaponins"). Two typical "asterosaponins" and
      ten glycosides of polyhydroxysteroids were instead isolated in relatively large
      amounts from E. brasiliensis. The asterosaponins include the known
      marthasteroside A1 [1] and the new brasiliensoside [2], while the glycosides of
      polyhydroxysteroids include seven new compounds (six monoglycosides and one
      diglycoside). The known echinasteroside A, previously found in Echinaster
      sepositus and in the related Henricia laeviuscula (both belonging to the family
      Echinasteridae), and laeviusculosides C and I from H. laeviuscula were also
      isolated. Most of the glycosides from E. brasiliensis are 3-O-beta
      xylopyranosides of delta 4-3 beta,6 beta,8,15 alpha,16 beta pentahydroxysteroid
      aglycones, having different side chains and sometimes a sulfate group at C-15,
      structural features which are typical of steroidal glycosides from starfishes of
      the family Echinasteridae. Continuing the analysis of the constituents of E.
      brasiliensis, we have also isolated a series of anthraquinones, known animal
      pigments found only in echinoderms and particularly in Crinoidea and in the
      Echinasteridae family of Asteroidea.

PMID- 8133301
TI  - Four new C16 1,2-dioxene-polyketides from the sponge Plakortis aff. simplex.
AB  - Two new cyclic peroxide-containing polyketide C16 acids 2 and 4 with their methyl
      esters 3 and 5 have been isolated from the Indo-Pacific marine sponge Plakortis
      aff. simplex. Both 2 and 3 are proposed to contain a single 1,2-dioxene ring,
      while 4 and 5 incorporate two 1,2-dioxene rings. The structures were elucidated
      mainly through 1D and 2D nmr spectral analysis. The methyl esters 3 and 5 were
      found to be active against cultured P-388 murine leukemia cells.

PMID- 8133302
TI  - On the structures of crambescins B and C1.
AB  - Revised structures have been assigned to the cyclic guanidine-containing
      crambescins B [3] and C1 [5], from the Mediterranean sponge Crambe crambe. The
      revisions were based on the fabms/cid/ms spectra of the [M+H]+ ions from
      crambescins B and C1 and hrfabms measurements on key fragment ions in the ms/ms
      spectra, which identify losses of C9H19 and C8H18N3O side-chains.

PMID- 8133303
TI  - Dose-related effects of cycloheximide on delayed neuronal death in the gerbil
      hippocampus after bilateral transitory forebrain ischemia.
AB  - Degeneration of dendrites followed by punctate chromatin condensation in the CA1
      area of the hippocampus is a characteristic of delayed neuronal death following
      bilateral forebrain ischemia. The effects of the protein synthesis inhibitor
      cycloheximide on delayed neuronal death following 20 min of bilateral forebrain
      ischemia were examined in the gerbil hippocampus at the 4th day of reperfusion.
      Low doses of cycloheximide beginning 10 min after ischemia (1.0 microgram/g body
      weight in saline followed by 1.0 microgram/g every 24 h) reduced the number of
      dying cells in the CA1 area, whereas high doses (2.0 micrograms/g, followed by
      1.0 microgram/g every 12 h) increased the number of dying cells. No effects were
      seen when a single dose of cycloheximide was injected 1 h before ischemia. These
      results indicate that the effects of cycloheximide are dose-dependent, low doses
      reduce, high doses increase cell death. These findings also indirectly suggest
      that protein synthesis may play a role in the extent of delayed neuronal death.
      Some involved proteins could be heat shock proteins, which are induced after
      ischemia and had been correlated with increased resistance to injury. However,
      changes of heat shock immunoreactivity in the postischemic hippocampus were not
      seen in the present study following cycloheximide injection.

PMID- 8133304
TI  - Cerebral vasomotor reactivity is significantly reduced in low-flow as compared to
      thromboembolic infarctions: the key role of the circle of Willis.
AB  - To test the hypothesis that cerebral vasomotor reactivity (CVMR) is significantly
      more reduced in patients with hemispheric low-flow infarctions than in brain
      infarctions due to arterio-arterial embolism, a series of 64 consecutive patients
      with internal carotid artery occlusions were studied. CVMR was calculated from
      relative changes of blood flow velocity within the middle cerebral artery (MCA)
      measured by transcranial Doppler ultrasonography (TCD) during hypo- and
      hypercapnia. The configuration of the circle of Willis (COW) was also determined
      by TCD using common carotid artery compression tests. Anterior, posterior or
      ophthalmic artery collateral flow, and absence or combinations of these, were
      differentiated. CT scans were categorized as showing either no infarction (group
      I; n = 20) or territorial (group II; n = 28), or low-flow infarctions (group III;
      n = 16). As compared to normal, CVMR was significantly reduced but equal in
      groups I and II, however, even more reduced in group III. CVMR was lowest, and
      low-flow infarctions were most frequent in patients whose collateral hemispheric
      blood supply was from the ophthalmic artery as opposed to patients with a
      complete or nearly complete COW. Our findings indicate that low-flow infarctions
      in extracranial ICA occlusions represent brain damage due to a critical reduction
      in cerebral perfusion pressure, as opposed to thromboembolically induced lesions.
      The configuration of the COW seems to play the key role. Our findings also
      support the view that the pattern of hemispheric infarction seen on CT indicates
      the pathogenesis of stroke.

PMID- 8133305
TI  - Prolonged effects of MK-801 in the cat during focal cerebral ischemia and
      recovery: survival, EEG activity and histopathology.
AB  - Previously we reported an improvement in histological outcome in cats treated
      with MK-801 shortly after the induction of temporary middle cerebral artery
      occlusion, and examined after 2 h of ischemia followed by 4 h of reperfusion.
      This study investigates the prolonged effects of the same drug treatment. Focal
      cerebral ischemia was produced in 34 cats by temporary occlusion of the left
      middle cerebral artery for 2 h. Stroke severity was determined using the ratio of
      the EEG amplitude from the ipsilateral to that of the contralateral hemisphere.
      Thirty minutes after the onset of ischemia, cats were treated i.v. with either 1
      mg/kg MK-801 or saline. Electrocortical activity of the animals who survived were
      followed for 6 days postocclusion at which point they were sacrificed for
      histopathological analysis. Twelve of the animals died during recovery, of which
      4 were MK-801 treated, and 8 were saline controls. The EEG ratios in the non
      surviving animals were more depressed than in the animals that survived, whereas
      the depression in the EEG amplitude in both the treated and the control surviving
      animals was equal. Among the survivors no reduction in infarct size with MK-801
      treatment was observed. Thus treatment with MK-801 in the middle cerebral artery
      occlusion model in the cat leads to a significant increase in the rate of
      survival (P < 0.05), but no prolonged improvement in late histopathology, in
      contrast with acute histological findings using this model. MK-801 treatment may
      be shifting the stroke model towards the survival of animals with larger
      infarcts. Histological recovery during prolonged reperfusion may eliminate the
      early neuroprotective effects seen with MK-801 treatment.

PMID- 8133306
TI  - Correspondence of increased debrisoquine 4-monooxygenase activity with seizure
      susceptibility in Mongolian gerbils.
AB  - Four drug-metabolizing activities in Wistar rat and Mongolian gerbil liver
      microsomes were investigated to clarify the biochemical basis of convulsions. No
      significant associations were observed between the susceptibility to the tonic
      clonic seizures in Mongolian gerbils and the drug-metabolizing enzymatic
      activities of p-nitroanisole O-demethylase, aminopyrine demethylase and
      benzo[a]pyrene-3-monooxygenase. However, a significant association was observed
      with the debrisoquine 4-monooxygenase (cytochrome P-450db1-linked monooxygenase
      system) activity, which is known to metabolize exogenous and endogenous
      parkinsonism-inducing neurotoxins such as MPTP and TIQ, and to activate
      carcinogens during the detoxication of xenobiotics. The mean activity of
      debrisoquine 4-monooxygenase in the seizure-sensitive group (male, 380; female,
      350 pmol/h/mg protein) remained significantly higher (about 4-5 times) than that
      in the seizure-resistant group (male, 90; female, 80 pmol/h/mg protein). More
      Mongolian gerbils were extensive metabolizers of debrisoquine in the seizure
      sensitive group than in the seizure-resistant group. These results suggest a
      possibility that the cytochrome P-450db1-linked monooxygenase system may activate
      the potential neurotoxins which are associated with tonic-clonic seizures in the
      Mongolian gerbil.

PMID- 8133307
TI  - Do patients with Down's syndrome recognize Mickey Mouse?
AB  - In 47 patients with Down's syndrome who were too retarded to understand a
      conventional oddball paradigm, we studied event-related potentials (ERPs) by
      using task-irrelevant visual stimuli. As the patients had expressed interest in
      Disney cartoons and books, five pictures of Disney characters such as Mickey
      Mouse or Peter Pan were employed as the rare stimuli, and nine ordinary scenes
      such as mountains as the frequent stimuli. Five sets were constructed by
      intermingling each rare picture with nine frequent pictures, and each picture was
      presented on a TV screen. ERPs to the rare stimuli (N270-P380), which were
      different from the averaged waveforms to frequent stimuli and electrooculograms
      (EOGs), were clearly recorded in 35 out of 47 patients. Only 24 of these patients
      had ERPs using a conventional auditory oddball paradigm. The peak latencies in
      patients were significantly prolonged relative to age-matched normal controls,
      probably due to a slowed neural processing. The amplitude in patients was
      slightly larger than normal controls, probably due to the patients' greater
      interest or surprise when confronted with the Disney characters.

PMID- 8133308
TI  - Alteration of muscarinic acetylcholine binding sites in the postischemic brain
      areas of the rat using in vitro autoradiography.
AB  - We studied the postischemic alteration of muscarinic acetylcholine binding sites
      in the rat brain using in vitro [3H]quinuclidinyl benzilate (QNB)
      autoradiography. Transient ischemia was induced by the occlusion of the middle
      cerebral artery (MCA) for 90 min and such occlusion followed by various
      recirculation periods of up to 4 weeks. After 90 min of ischemia followed by 3
      days of recirculation, [3H]QNB binding sites were found to be significantly
      decreased in the cerebral cortex (P < 0.01) and lateral segment of the caudate
      putamen (P < 0.05), both supplied by the occluded MCA; thereafter, the binding
      sites decreased progressively in those ischemic foci. Moreover, 3 days after the
      ischemia, significant decreases of [3H]QNB binding sites were observed in the
      ipsilateral thalamus and the amygdala, and also in the substantia nigra 1 week
      after the ischemia, areas which had not been directly affected by the original
      ischemic insult. This postischemic phenomenon observed in the thalamus and the
      substantia nigra developed concurrently with 45Ca accumulation, which was
      detected there in our previous study. These results indicate that alteration of
      muscarinic acetylcholine binding sites may be involved not only in the ischemic
      foci, but also in the exo-focal remote areas, in which delayed neuronal
      degeneration due to neuronal network disturbances after the ischemia was
      observed. We suggest that multifocal postischemic alterations of muscarinic
      acetylcholine binding sites may exacerbate the clinical symptoms of patients
      during the chronic stage of stroke.

PMID- 8133309
TI  - Progression of kaolin-induced hydrocephalus and changes in performance of operant
      tasks by rats.
AB  - The behavior of rats with progressive hydrocephalus was examined to detect early
      neurological deterioration. Kaolin solution was injected into the cisterna magna
      of 10 of 17 anesthetized 8-week-old male rats (day 0), and saline in the other 7
      rats (control group). Reaction time (RT, sec) and error ratio (ER, %) of
      unanesthetized rats escaping from electrical stimuli toward a nonstimulated sheet
      within a box were recorded daily from day 4 until autopsy after 4 weeks. Three
      rats in the kaolin group died in acute stage. Rats were assigned to either severe
      (S) (n = 4) or moderate (M) (n = 4) group according to the degree of ventricular
      dilatation at autopsy. The RTs prolonged and ERs increased in the kaolin group
      and they reached their minimum values. Values after the minimum RT value on day
      12 in the M-group and 22 in the S-group during the chronic stage were compared
      with those in the controls, which decreased throughout the experiments (P <
      0.03). In all animals in the S-group RT was prolonged each day with a linear
      regression (P < 0.005), although ER was decreased (0.69 > P > 0.23). In 3 rats
      and in another rat in the M-group RT was prolonged (P < 0.04 and P = 0.19) and ER
      was decreased in 3 rats (two: P = 0.41; one: P = 0.01) and increased in one (P =
      0.55). In conclusion, deteriorated motor function is more important for early
      diagnosis in progressive hydrocephalus than behavioral symptoms.

PMID- 8133310
TI  - gamma delta+ T cells are increased in patients with Parkinson's disease.
AB  - The etiology of Parkinson's disease is mainly unknown. Immune abnormalities have
      been reported, including the occurrence of autoantibodies against neuronal
      structures and abnormal T cell functions. gamma delta+ T cells represent a
      recently recognized T cell subpopulation which is considered to play a role in
      immune responses in infections and autoimmunity. We examined by three-colour flow
      cytometry the proportions of gamma delta+ T cells in blood and cerebrospinal
      fluid (CSF) from patients with Parkinson's disease. Increased proportions of
      gamma delta+ T cells were found in CSF in Parkinson's disease compared to other
      neurological diseases (OND) and tension headache. In peripheral blood, patients
      with Parkinson's disease had higher numbers of gamma delta+ T cells compared to
      OND patients. No differences between gamma delta+ T cells in CSF compared to
      blood were demonstrable in the individual patient groups. CD25 was not expressed
      on gamma delta+ T cells in blood of the majority of cases, but 50% of patients
      with Parkinson's disease and 30% with OND and tension headache had CD25+ gamma
      delta+ T cells in CSF arguing for a preferential activation of gamma delta+ T
      cells in the CSF compartment. Whether the elevated gamma delta+ T cell population
      in Parkinson's disease reflects previously unrecognized inflammation or may occur
      also in non-inflammatory disorders remains to be elucidated.

PMID- 8133311
TI  - Decreased cerebrospinal fluid nitrate levels in Parkinson's disease, Alzheimer's
      disease and multiple system atrophy patients.
AB  - Nitric oxide (NO) is a recently discovered endogenous mediator of vasodilatation,
      neurotransmission, and macrophage cytotoxicity. NO is thought to have a function
      in memory and in long-term potentiation. At high concentrations NO is neurotoxic
      and may play a role in neurodegeneration. NO is formed from L-arginine by the
      enzyme NO synthase (NOS), for which tetrahydrobiopterin (BH4) is a necessary co
      factor. Alzheimer's disease (AD) and, to a lesser degree, Parkinson's disease
      (PD) are thought to be associated with increased microglial activity, suggesting
      that NO production may be increased. Alternatively, in circumstances of reduced
      levels of intracellular L-arginine or BH4, NO production is diminished and
      neurotoxic oxygen radicals may be produced. Since BH4 is decreased in AD and PD
      brains, these diseases may be associated with decreased NO production. We
      investigated these two alternatives by measuring the NO degradation products
      nitrite and nitrate in cerebrospinal fluid (CSF) of PD (n = 103), AD (n = 13),
      and multiple system atrophy (MSA; n = 14) patients and controls (n = 20). We
      found for all patient groups, compared with controls, significantly decreased
      levels of nitrate, but not nitrite. This finding seems to indicate a decreased NO
      production of the central nervous system (CNS) in these neurodegenerative
      disorders.

PMID- 8133312
TI  - Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited
      disease.
AB  - We report the clinical findings in 19 Finnish patients, including six pairs of
      siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive
      clinical symptoms manifested between one and two years of age in previously
      healthy infants. The first manifestation of children at that age was clumsiness
      and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of
      deep tendon reflexes were discovered on clinical examination. By school age
      ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy
      developed by adolescence. In addition, an acute crisis with status epilepticus
      was a late manifestation. We found a marked decrease in sensory nerve condition
      velocities, a progressive loss of myelinated fibers in sural nerve specimen, and
      abnormal background activity in EEG with advancing age. The main finding in
      neuroradiological investigations was cerebellar atrophy. The occurrence of the
      disease in siblings and lack of manifestations in parents indicate recessive
      inheritance.

PMID- 8133313
TI  - Mitochondrial DNA mutation underlying Leigh's syndrome: clinical, pathological,
      biochemical, and genetic studies of a patient presenting with progressive
      myoclonic epilepsy.
AB  - An 18-year-old male patient presented with clinical and radiological evidence of
      Leigh's syndrome (LS), having developed progressive myoclonic epilepsy and ataxia
      11 years previously. Muscle biopsy showed cytochrome oxidase deficiency but no
      ragged red fibres. Autopsy confirmed the diagnosis of LS; there was additional
      degenerative change in the cerebellum and dentate and olivary nuclei, and an
      axonal peripheral neuropathy. Biochemical studies showed reduced activity of
      complexes I and IV of the respiratory chain in mitochondria from heart, liver and
      kidney. The mutation of mitochondrial DNA (mtDNA) at position 8344, commonly
      associated with the syndrome of myoclonic epilepsy and ragged red fibres, was
      detected in the patient's blood and was present in muscle, brain, liver, heart,
      and kidney in uniformly high amounts. It is clear that LS is genetically
      heterogeneous and represents one of the most severe phenotypes of a number of
      different mtDNA defects.

PMID- 8133314
TI  - A new gerbil model of hindbrain ischemia by extracranial occlusion of the
      bilateral vertebral arteries.
AB  - A new gerbil model of hindbrain ischemia was induced by extracranial occlusion of
      the bilateral vertebral arteries just before their entry into the transverse
      foramen of the cervical vertebra. Carbon black studies, performed at 5 min after
      occlusion, revealed that the pons-medulla oblongata, and the cerebellum were
      quite ischemic in all animals. Cardiovascular changes in mean arterial blood
      pressure (MABP) and heart rate were recorded until 30 min after occlusion, and
      revealed that the typical cerebral ischemic response (i.e., abrupt increase in
      MABP, bradycardia, and apnea) was elicited in all animals (n = 10). Thirty
      minutes after occlusion, animals (n = 4) were decapitated and immersion-fixed.
      Brain sections were stained with hematoxylin-eosin (HE) and also immunostained
      for microtubule-associated protein 2 in order to evaluate ischemic neuronal
      damage from 30 min of ischemia. By HE staining, ischemic lesions were detected
      bilaterally in the oculomotor, the trigeminal motor, the lateral vestibular, and
      the cerebellar interpositus nucleus. In addition, immunostaining revealed
      ischemic lesions in several other hindbrain areas. In conclusion, we could
      successfully establish a new gerbil model of hindbrain ischemia. Carbon black
      perfusion and hemodynamic studies revealed that severe and reproducible hindbrain
      ischemia was produced. By histopathological examination, we could also clearly
      demonstrate symmetrical ischemic lesions in several hindbrain areas.

PMID- 8133315
TI  - Formulas for the quantitation of intrathecal IgG production. Their validity in
      the presence of blood-brain barrier damage and their utility in multiple
      sclerosis.
AB  - There are several formulas for the quantitative determination of intrathecal IgG
      production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index,
      Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG
      index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To
      evaluate the utility of these formulas in the presence of blood-brain barrier
      (BBB) damage, we present the results from a study of serum and cerebrospinal
      fluid (CSF) samples from 125 healthy individuals, 18-88 years of age; 1072
      consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without
      BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin
      ratio 9.8-30); and 106 patients with definite multiple sclerosis (MS). The
      relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably
      linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without
      oligoclonal bands in the CSF (r = 0.95; P < 0.0001). Therefore, IgG(loc) and the
      Extended IgG index, two formulas based on a nonlinear relation between the CSF/S
      albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in
      the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values
      in the presence of BBB damage, probably because of incorrect constants in these
      formulas. There were no significant correlations between the CSF/S albumin ratio
      (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless
      quotients for the detection of intrathecal IgG production, or between the CSF/S
      albumin ratio and IGGPROD, an empirical formula for the determination of
      intrathecal IgG production in mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133316
TI  - Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic
      function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly).
AB  - We report the characteristics of one patient and two asymptomatic carriers from a
      Japanese family with familial amyloidotic polyneuropathy (FAP). The clinical
      features were somatic sensory and motor neuropathy with well-preserved autonomic
      function and late onset with slow insidious progression. These symptoms and signs
      are different from those of type 1 FAP. There were massive amyloid deposits with
      transthyretin (TTR) in the myocardium and the sural nerve. DNA sequencing of the
      TTR gene and amino acid sequence analysis of serum TTR revealed a new mutation in
      which Gly97 was substituted for Ala. We suggest that patients with somatic
      sensory and motor neuropathy of unknown origin without apparent autonomic
      dysfunction should be further studied for TTR mutation.

PMID- 8133317
TI  - Values and the for-profit healthcare industry. An uneasy fit.

PMID- 8133318
TI  - Values and the for-profit healthcare industry. A manageable issue.

PMID- 8133319
TI  - Resources used by nurse administrators in ethical decision-making.

PMID- 8133320
TI  - Development of an innovative nursing care delivery system.
AB  - In the reform of healthcare lies its renaissance, and in its challenges lie its
      opportunities. Faced with the changing needs of consumers, the evolving roles of
      care givers, technologic advances, and economic pressures, institutions are
      redesigning their physical facilities and systems of care delivery in preparation
      for a new era in healthcare. Innovative care delivery systems, developed to
      complement creative facility designs, will provide an approach to health-care
      that promotes administrative efficiency, patient/care giver satisfaction, and
      cost-effective use of resources. This article chronicles the development of a
      care delivery system for obstetric nursing, a blueprint for future healthcare at
      one institution.

PMID- 8133321
TI  - Physical restraints--implications for administrators.

PMID- 8133322
TI  - Case management and nursing practice.
AB  - Does adopting a case management model alter nursing practice? The authors examine
      the effect case management has on nurse-client relationships and nurse-colleague
      relationships and explore how nurses are using case management as a vehicle to
      achieve professionalism. The article is based on a literature review of case
      management for community-dwelling elderly residents and interviews with 17
      community-based nurses practicing as case managers in Canada.

PMID- 8133323
TI  - Integrating quality assurance and total quality management/quality improvement.
AB  - Hospitals have joined other industries in the quest for quality improvement. Most
      healthcare organizations have processes in place to meet the quality assurance
      standards of the Joint Commission on Accreditation of Healthcare Organizations.
      The challenge is to integrate these two similar, but different, structures into
      one efficient and effective mechanism for quality. One hospital's effort to
      develop a pilot program to combine total quality management/quality improvement
      and quality assurance in a cost-effective and efficient manner is described.

PMID- 8133324
TI  - Stop floating--the next paradigm shift?

PMID- 8133325
TI  - Evaluation of a program to improve nursing assistant use.
AB  - To enable registered nurses to devote more time to planning and coordinating
      care, a hospital-wide program was implemented to improve nursing assistant use
      and productivity. After implementation of the program, registered nurses noticed
      a decreased work load, improved quality of nursing care, and increased ability to
      supervise assistants. In addition, trended data suggest improved quality of
      nursing care and patients satisfaction.

PMID- 8133326
TI  - An outcome-focused, community-based health support program.
AB  - The authors discuss an outcome-based management framework for evaluating a
      community-based program for children requiring health support. Application of the
      framework is delineated both generically and specifically. Examples illustrate
      the process of global outcomes analysis and identification of critical outcomes,
      activities, and strategies.

PMID- 8133327
TI  - Breaking down the walls without tearing down the house.

PMID- 8133328
TI  - The nurse executive in the public sector. Responsibilities, activities, and
      characteristics.
AB  - Most published research on the role of the nurse executive has occurred in the
      private sector. The authors expand our knowledge by reporting nurse executive
      practice in the public sector, specifically the Department of Veterans Affairs.

PMID- 8133329
TI  - An introduction to the Internet. Part I: History, structure, and access.

PMID- 8133330
TI  - Development of an instrument to measure effectiveness of clinical instructors.
AB  - Evaluation of clinical instructors by their students is an important issue in
      nursing education. This study describes the outcome of the development of a
      method by which nursing students can evaluate their clinical instructors with a
      reliable and valid instrument. The instrument was developed using characteristics
      from the literature, which were rated in importance by students, faculty, and new
      graduates. The ratings are then subjected to statistical analysis using
      frequency, means, alpha coefficient, and item-to-total correlation and expert
      assessment to provide reliability and validity for the instrument and to aid in
      reducing the original list of 50 characteristics to a more usable number of 27.
      The instrument is pilot tested once with students rating clinical faculty.
      Results from the pilot are provided.

PMID- 8133331
TI  - Description of a stressful encounter: appraisal, threat, and challenge.
AB  - The purpose of this study was to examine a potentially stressful event for
      students, the midterm examination, using the Lazarus transactional stress model.
      At two time periods during an academic term, 50 students responded to
      questionnaires focused on the midterm examination and its outcome. Responses were
      used to identify changes in appraisals, personal stakes, perceptions of threat
      and challenge; to determine these variables' relations to each other and to the
      examination grade; and to determine the best predictors of threat, challenge, and
      grade. Results indicated that threat and challenge perceptions were the only
      variables that changed as the situation evolved; they were negatively correlated.
      The best predictor of threat and challenge was control, while the only variable
      that correlated with grade was harm.

PMID- 8133332
TI  - National survey of nursing program options designed for the second degree
      student.
AB  - There is a current trend for schools of nursing to begin second degree options.
      Given the current economic situation, this is a win/win situation that benefits
      the second degree student, schools of nursing, the profession, and the community
      in general.

PMID- 8133333
TI  - Are nursing students multiculturally competent? An exploratory investigation.

PMID- 8133334
TI  - Critical thinking ability of nurse educators and nursing students.

PMID- 8133335
TI  - The second time around: nursing as a second degree.

PMID- 8133337
TI  - Learning experiences in a rural family homeless shelter.

PMID- 8133336
TI  - The use of the humanities in psychiatric nursing education.

PMID- 8133338
TI  - Meeting the challenge of the curriculum revolution: problem-based learning in
      nursing education.
AB  - Nursing education today faces a great challenge as it reviews the outcomes of
      traditional teaching strategies and seeks to explore new alternatives in
      preparing the nursing student for the complex and diverse profession of nursing.
      Problem-based learning is one alternative to meeting the needs of a society with
      health requirements as diverse as its population. Nurses must be capable of
      exploring options, asking questions, articulating explanations, and developing
      appropriate nursing care plans based on reflective decisions. They must continue
      to value learning throughout their careers to maintain their expertise. The role
      of the educator today is to probe student thinking toward conceptual
      understanding, to increase depth of subject knowledge, to provide student
      learning opportunities, and, by encouraging the articulation and contrasting of
      different points of view, to allow the emergence of common understandings. A
      problem-based curriculum can provide the framework for the revolution in nursing
      education to occur.

PMID- 8133339
TI  - The teamwork project: a collaborative approach to learning to nurse families.
AB  - The purpose of this exploratory study was to gain insight into students'
      perceptions of learning to nurse families using a team approach. A sample of 112
      third-year baccalaureate nursing students provided data from clinical journals
      and responses to a teacher-developed questionnaire regarding number of home
      visits made with a partner, the extent to which partners shared responsibility
      for the nursing care of two families, perceived benefits and disadvantages of
      teamwork, roles assumed by team members, perceived outcomes of the team approach,
      and suggestions for revision of the approach. The degree to which students shared
      responsibility was moderate and positive perceptions of teamwork were
      significantly correlated with the degree of sharing of nursing activities. Using
      Spradley's qualitative method of domain analysis, interpretation of data from
      students' clinical journals revealed subjective aspects of the experience that
      appeared to influence teamwork practices and attitudes. Results suggest that the
      shared assignment approach offers students a unique opportunity to learn about
      the realities of collaborative nursing practice.

PMID- 8133340
TI  - The nursing research internship program: providing research training in the
      clinical setting.
AB  - Today's changing health care delivery system with its emphasis on restructuring
      patient care services requires of nursing greater accountability for patient care
      services and a more careful and systematic examination of patient outcomes.
      Nursing research can help the profession meet these challenges. The New York City
      Health & Hospitals Corporation's Nursing Research Internship Program gives nurses
      an opportunity to become involved in research and serve as research resources to
      their colleagues. This program offers instruction in research methods,
      development and conduct of a research project, and participation in ongoing
      research activities.

PMID- 8133341
TI  - Cooperative learning as an approach for educating diabetic patients and their
      spouses.
AB  - The purpose of this quasi-experimental pilot study was to investigate the
      effectiveness of applying cooperative learning theory when educating persons with
      diabetes and their spouses. The target population were patient-spouse pairs who
      had attended a diabetic outpatient program within the past 2 years. Members of
      the experimental group employed cooperative learning strategies to review
      information about diabetes; members of the control group were provided with a
      lecture reviewing information about diabetes. Results suggested an increase in
      knowledge about diabetes in both groups. Although the experimental group reported
      a favorable attitude toward cooperative learning, the results did not demonstrate
      that the cooperative learning instructional method contributed to more improved
      learning than the lecture method. Limitations of the study methodology are
      discussed to better understand the results.

PMID- 8133342
TI  - Prediction of nosocomial infections in cardiac patients: a pilot study.
AB  - The purpose of this descriptive pilot study was to discover and correct problems
      with data collection in the identification of variables that are the strongest
      predictors of the occurrence of four nosocomial infections in cardiac patients.
      Data from 29 subjects who were admitted to a critical care unit (CCU) were
      tracked at a health care facility located in upstate New York. Data were obtained
      from daily care flow sheets and patients' charts. Although most results were not
      statistically significant, trends were identified in the data. The 7 patients who
      developed nosocomial infections were men who were older than 50 years, underwent
      a cardiac surgical or other invasive procedure, had more than one intravenous
      catheter, experienced a significant event in the CCU, and received prophylactic
      antibiotics. It is recommended that the number of independent variables tracked
      be reduced to 20. In addition, readmission of subjects whose data are being
      tracked should be included.

PMID- 8133343
TI  - Survey of nursing research in New York state: XV.

PMID- 8133344
TI  - Bridging the nursing research-practice gap through research utilization.
AB  - This article explores the gap that currently exists between nursing research and
      nursing practice. The aim is to promote the conversion of new knowledge into
      practical innovations. Barriers to research utilization in practice settings come
      from both the academic and clinical arenas. Innovative models and strategies are
      needed to overcome these barriers. The purposes and value of research utilization
      and the clinical and academic strategies that facilitate research are discussed.
      Supporting clinical studies are provided as exemplars.

PMID- 8133346
TI  - How do physicians weigh iatrogenic complications?
AB  - OBJECTIVE: To determine how physicians weigh iatrogenic complications when making
      clinical decisions. DESIGN: Physicians were mailed a questionnaire describing two
      simplified scenarios--one involving a patient with a cerebral embolism and the
      other involving a patient with a life-threatening arrhythmia. In each scenario
      there was one potential natural adverse outcome (which could be prevented with
      drug therapy) and one potential drug side effect (iatrogenic adverse outcome),
      which would be clinically indistinguishable from the natural adverse outcome.
      Half the respondents were given the probability of the natural adverse outcome
      (PN) and were asked to specify the probability of the iatrogenic adverse outcome
      (PI) at which they felt that giving and withholding the therapy were equivalent
      strategies. The other respondents were given the PI and asked to specify the PN
      at which they felt the two strategies were equivalent. SETTING: Academic medical
      center. PARTICIPANTS: Staff physicians. MEASUREMENTS AND MAIN RESULTS: Results
      are expressed as the ratio PI/PN at which the respondent felt that giving and not
      giving therapy were equivalent strategies. A ratio less than 1 indicates that
      errors of commission (iatrogenic adverse outcomes) were given more weight than
      were errors of omission (natural adverse outcomes when therapy was withheld).
      Ratios less than 1 were provided in 56% of the responses (n = 230). The mean
      PI/PN in the group with ratios less than 1 was 0.53 +/- 0.26 (SD; n = 129).
      CONCLUSIONS: In making decisions, some physicians appear to weigh errors of
      commission more heavily than they do errors of omission, while others weigh them
      equally. This diversity of physicians' attitudes may explain some of the
      variation observed in clinical practice in settings where The possibility of
      iatrogenic complications is of concern.

PMID- 8133345
TI  - Quality of published reports of the prognosis of community-acquired pneumonia.
AB  - OBJECTIVE: To systematically assess the quality of published reports of the
      prognosis of community-acquired pneumonia using a formal quality assessment
      instrument. DESIGN: Retrospective review of studies published during 1966-1991.
      ARTICLES: 108 articles related to the prognosis of community-acquired pneumonia
      retrieved by a computerized search. INTERVENTION: All articles, blinded to
      author(s), journal title, year of publication, and study institution(s), were
      independently reviewed by two investigators using a ten-item quality assessment
      instrument designed to evaluate: 1) identification of the inception cohort (4
      items), 2) description of referral patterns (1 item), 3) subject follow-up (2
      items), and 4) statistical methods (3 items). Adherence to each of the ten
      individual quality items and an overall quality score were calculated for all
      articles and across three time periods. MAIN RESULTS: Among all 108 articles that
      underwent quality assessment, 30 were published from 1966 to 1979, 61 from 1980
      through 1989, and 17 from 1990 through 1991. The mean total quality score of all
      articles was 0.55 (range 0.22-0.90). There was a significant trend toward
      improvement in total quality scores over the three time periods (0.50 to 0.56 to
      0.65; p < 0.001). However, several systematic errors in the study design or
      reporting of these studies were discovered throughout time: only 3.7% provided
      comparative information about nonenrolled patients, 28.7% determined whether the
      study institution was a referral center, 36.1% specified inclusion or exclusion
      criteria, and 45.5% used appropriate statistical analyses to adjust for more than
      one prognostic factor. CONCLUSIONS: Despite improvement in overall quality of
      published articles, systematic errors exist in the design and reporting of
      studies related to the prognosis of community-acquired pneumonia. The quality
      assessment tool employed in this study could be used to guide the development of
      high-quality outcomes research in the future.

PMID- 8133347
TI  - "Oh, by the way ...": the closing moments of the medical visit.
AB  - OBJECTIVE: To define and describe the communication between physicians and
      patients in the closing phase of the medical visit. To identify types of
      communication throughout the visit that are associated with the introduction of a
      new problem during the closing moments of the visit or with longer closures.
      DESIGN: Audiotaping of office visits. Tapes were analyzed using a modified Roter
      Interactional Analysis System (RIAS). The coders' definition of closure was
      compared with the opinion of communication experts. SETTING: Outpatient offices
      of practicing physicians. PARTICIPANTS: Eighty-eight patients visiting 20 primary
      care physicians participated. Physicians were selected by a letter from the
      Oregon Board of Medical Examiners. The mean number of years from graduation was
      16 (range 3-47). One physician per site participated. MEASUREMENTS: Frequencies
      of physician and patient communication behaviors and global affect scores were
      calculated and correlations were drawn using t-test and chi-square analyses.
      RESULTS: The physicians initiated the closing in 86% of the visits. The
      physicians clarified the plan of care in 75% of the visits and asked whether the
      patients had more questions in 25% of the cases. The patients introduced new
      problems not previously discussed in 21% of the closures. New problems in closure
      were associated with less information exchanged previously by physicians and
      patients about therapy (t = -3.28, p = 0.002; t = -2.26, p = 0.03), fewer
      orientation statements by physicians (t = 1.86, p = 0.001), and higher patient
      affect scores (t = 0.252, p = 0.016). Long closures (> 2 minutes) correlated with
      physicians' asking open-ended questions (0.2438; p = 0.019), laughing (0.3002; p
      = 0.005), showing responsiveness to patients (0.3996; p < 0.001), being self
      disclosing (0.3948; p < 0.001), and engaging in psychosocial discussion with
      patients (0.2410; p = 0.020). CONCLUSION: This study is the first description of
      how physicians and patients communicate during the closing of office visits.
      Notably, the patients raised new problems at the end of the visit in 21% of the
      cases. The findings suggest ways physicians might improve communication in the
      closing phase of the medical interview. Orienting patients in the flow of the
      visit, assessing patient beliefs, checking for understanding, and addressing
      emotions and psychosocial issues early on may decrease the number of new problems
      in the final moments of the visit.

PMID- 8133349
TI  - Relationship between symptoms and health-related quality of life in chronic lung
      disease.
AB  - The authors studied the relationship between patient self-reported symptoms and
      responses to a general measure of health-related quality of life [Short Form 36
      (SF-36)] for 102 patients who had chronic lung disease [forced expiratory volume
      in one second (FEV1) < 70%]. The primary diagnoses were chronic bronchitis,
      emphysema, and asthma; the mean age was 62 years, and 46% were women. Based upon
      Medical Research Council (MRC) symptom scores, the patients' disease severity was
      classified as mild (21%), moderate (22%), or severe (57%). The SF-36 scores
      differed significantly between disease severity groups in domains of health
      perception, physical functioning, physical role, and energy. The SF-36 physical
      functioning and Oxygen Cost Diagram scores correlated well (r = 0.78). The
      authors conclude that SF-36 is a useful and valid measure of general health
      status in patients with chronic lung disorders.

PMID- 8133350
TI  - Which advance directive do patients prefer?
AB  - This study examined patient acceptance of two different advance directives.
      Outpatients completed the two directives and a 12-item acceptability
      questionnaire for each, and then stated their directive preferences. Of 128
      patients enrolled, 97 (76%) responded. Overall, 47% of the respondents were
      satisfied with the Let Me Decide directive and 53% with the Medical Directive
      (NS). Thirty-nine percent preferred the Let Me Decide directive, 37% preferred
      the Medical Directive, and 25% had no preference or were uncertain which they
      preferred. Although there was no difference in patient acceptance between the
      directives, 76% of the patients preferred one or the other. Therefore, different
      people like different directives, and a variety of directives should be available
      for patients to review before they complete one.

PMID- 8133351
TI  - Deciphering the physician note.
AB  - Objective information about legibility of physician handwriting is scant. This
      retrospective chart review compared handwritten general medicine clinic chart
      notes from internal medicine faculty and housestaff with their typed
      counterparts. The written counterparts took 11 seconds (46%) longer to read and 5
      seconds (11%) longer to answer comprehension questions. The authors'
      comprehension measure (developed specifically for ambulatory clinic notes) was
      only slightly higher for typed notes. The legibility of physician handwriting is
      not as dismal as assumed; physicians can effectively communicate on paper.

PMID- 8133348
TI  - Primary care of the renal transplant patient.

PMID- 8133352
TI  - Health care reform and funding of graduate medical education.

PMID- 8133353
TI  - Providing CPR survival data to patients.

PMID- 8133354
TI  - Counseling youths about firearms.

PMID- 8133355
TI  - Validation of a clinical prediction rule for the differential diagnosis of acute
      meningitis.
AB  - OBJECTIVE: To attempt to validate a previously reported clinical prediction rule
      derived to assist in distinguishing between acute bacterial meningitis and acute
      viral meningitis. DESIGN: Retrospective chart review of patients treated at five
      hospitals between 1981 and 1990. The criterion standard for bacterial meningitis
      was a positive cerebrospinal fluid (CSF) or blood culture or a positive test for
      bacterial antigen in the CSF. For viral meningitis, the criterion standard was a
      positive viral culture from CSF, stool, or blood or a discharge diagnosis of
      viral meningitis with no other etiology evident. SETTING: Two Department of
      Veterans Affairs (VA) hospitals, two county hospitals, and one private hospital,
      each affiliated with one of two medical schools. PATIENTS: All persons aged more
      than 17 years who were hospitalized over a ten-year period at one of five
      academically affiliated hospitals for the management of acute meningitis.
      MEASUREMENTS AND MAIN RESULTS: Sixty-two cases of bacterial meningitis and 98
      cases of viral meningitis were confirmed. With all patients included, the
      discriminatory power of the model as measured by the area under the receiver
      operating characteristic curve (AUC) was 0.977 (95% CI, 0.957-0.997), compared
      with the AUC of 0.97 in the derivation set of the original publication. The AUCs
      (95% CIs) for data subsets were: Dallas cases 0.994 (0.986-1.0). Milwaukee cases
      0.912 (0.834-0.990); ages 18-39 years 0.952 (0.892-1.0), ages 40-59 years 0.99
      (0.951-1.0), and age > or = 60 years 0.955 (0.898-1.0). CONCLUSIONS: The authors
      conclude that the clinical prediction rule proved robust when applied to a
      geographically distinct population comprised exclusively of adults. There was
      sustained performance of the model when applied to cases from each city and from
      three age strata. Prospective validation of this prediction rule will be
      necessary to confirm its utility in clinical practice.

PMID- 8133356
TI  - Perimenopause.

PMID- 8133357
TI  - Clinical advances in the management of severe nausea and vomiting during
      pregnancy.
AB  - The nutritional status of the woman with hyperemesis of pregnancy has been
      compromised by decreased food intake and increased nutrient loss. Depending on
      the severity of symptoms, interventions may begin with dietary and life-style
      alterations, proceed to oral nutritional supplementation or pharmacologic
      preparations, and continue on to intravenous vitamin-mineral therapy and either
      enteral tube feedings, parenteral nutrition, or both. These therapies, and the
      role of the nurse in initiating or supporting them, are described.

PMID- 8133358
TI  - Preventing neonatal hepatitis B infection during the perinatal period.
AB  - In the United States, hepatitis B virus (HBV) infection is a growing problem with
      serious long-term consequences. Because previous vaccination programs have been
      ineffective in lowering the incidence of HBV, the U.S. Centers for Disease
      Control now recommend a comprehensive plan to reduce transmission of the virus.
      This article explores the epidemiology of HBV infection, the use of hepatitis B
      immune globulin and hepatitis B vaccines, and current recommendations for
      eliminating transmission of HBV during the perinatal period.

PMID- 8133359
TI  - Severe preeclampsia: implications for critical-care obstetric nursing.
AB  - Severe preeclampsia can have a catastrophic effect on maternal-fetal outcome;
      therefore, perinatal nurses must have a working knowledge of related
      pathophysiologic processes to perform advanced assessment and interpret data.
      Technologic adjuncts developed over the past decade, such as the fiberoptic
      pulmonary artery catheter, allow more precise assessment of maternal hemodynamic
      status and oxygenation for some patients. With such information, the health-care
      team can guide therapy to promote optimal outcomes.

PMID- 8133360
TI  - Prevalence of drug use among pregnant women in a rural area.
AB  - OBJECTIVE: To determine the prevalence of alcohol and illegal drug use among
      pregnant women in a rural midwestern area. DESIGN: Descriptive, prospective
      study. SETTING: Private tertiary medical center in a rural midwestern area.
      PARTICIPANTS: A nonprobability convenience sample of 202 women enrolling for
      prenatal care. MAIN OUTCOME MEASURES: Hypothesized that the prevalence of alcohol
      and illegal drug use by pregnant women in a rural midwestern area may be similar
      to the prevalence in urban areas. RESULTS: The prevalence for perinatal drug use
      among the sample was 3.9%, with a 95% exact binomial confidence interval of 1.7%
      to 7.7%. CONCLUSIONS: The 3.9% prevalence level is significantly lower than the
      11% prevalence levels projected by urban studies (p = .0006). Additional studies
      need to be conducted on rural populations, however, with periodic testing
      performed throughout pregnancy. Further studies should examine, through self
      reporting, prevalence rates of tobacco and alcohol use during pregnancy.

PMID- 8133361
TI  - Appraisal, coping, and emotional health of infertile couples undergoing donor
      artificial insemination.
AB  - OBJECTIVES: To describe differences between wives and husbands undergoing donor
      artificial insemination (AID), in terms of stress level, factors contributing to
      the stress of AID, cognitive appraisal of AID, ways of coping, and emotional
      health. DESIGN: Descriptive correlational. SETTING: A gynecology-endocrinology
      clinic at a university hospital and a private infertility practice in the
      midwestern United States. PARTICIPANTS: Forty wives and thirty-five husbands
      participating in AID. MAIN OUTCOME MEASURES: Perceived level of stress, factors
      contributing to the stress of AID, appraisal of AID, revised ways of coping, and
      profile of mood states. RESULTS: Wives had greater stress levels, used more ways
      of coping, and more often appraised AID as a harm-loss, threat, or challenge.
      Husbands more often appraised AID as a beneficial experience. Individuals who
      appraised AID differently differed in emotional health and levels of stress.
      CONCLUSIONS: Investigations into the relationships among stress levels,
      stressors, appraisal, coping, situational factors, and emotional health will help
      nurses understand how these factors affect the health of couples undergoing AID.

PMID- 8133363
TI  - Dual commitment in practice and research.

PMID- 8133362
TI  - Multidimensional pain assessment in premature neonates: a pilot study.
AB  - OBJECTIVE: To describe the physiologic and behavioral responses of premature
      neonates to a painful stimulus. DESIGN: Descriptive. SETTING: Secondary-level
      neonatal unit in a large metropolitan university teaching hospital. PARTICIPANTS:
      Forty neonates between 32 and 34 weeks' postconceptual age and less than 5 days'
      postnatal age. MAIN OUTCOME MEASURES: Physiologic (heart rate, oxygen saturation,
      and intracranial pressure) and behavioral (facial expression and cry) outcomes
      observed during a routine heel stick. RESULTS: Physiologic responses were
      significant, but were not specific to pain. Behavioral responses were more
      promising and indicated that premature neonates were capable of responding in a
      manner similar to full-term neonates. CONCLUSIONS: Premature neonates are capable
      of expressing their pain in a manner similar to healthy, full-term neonates.
      Factors that alter this response were not clearly delineated. Further research is
      needed to determine more precise patterns of response in this age group.

PMID- 8133364
TI  - Tumescent technique in cervicofacial rhytidectomy.
AB  - The tumescent technique of local anesthetic administration was originally spawned
      by the desire to facilitate full-body, large volume liposuction in a safe and
      efficient outpatient manner. The numerous advantages of this technique are
      readily applied to cervicofacial rhytidectomy. The method described creates an
      essentially bloodless field via hydrodissection with overall decreased surgical
      morbidity secondary to the decreased necessity of sharp surgical dissection.

PMID- 8133365
TI  - Modified double mandibular osteotomy for tumors of the parapharyngeal space.
AB  - In 1984, Attia et al described the double mandibular osteotomy as a more direct
      approach for tumors of the ptergomaxillary and parapharyngeal space. The
      procedure incorporates the traditional parasymphyseal osteotomy of the mandible
      with a horizontal osteotomy of the ascending ramus. Several modifications of this
      technique are described that increase the surgical exposure, while requiring less
      surgical dissection. The incorporation of rigid fixation with miniplates has
      improved postoperative recovery by avoiding maxillomandibular fixation and
      improving oral nutrition.

PMID- 8133366
TI  - Surgical versus nonsurgical treatment of unilateral dislocated low subcondylar
      fractures: a clinical study of 52 cases.
AB  - To compare open versus closed reduction of unilaterally dislocated low
      subcondylar fractures in adults, 101 consecutive dentulous patients were treated
      either by closed reduction with a median of 4 weeks of maxillomandibular
      fixation, or with a median of 6 weeks of maxillomandibular fixation after
      surgical repositioning and transosseous wiring of the dislocated condylar
      fragment. No selection of patients was done for either treatment. Fifty-two
      patients were seen at a median of 2 years postoperatively. Complications such as
      malocclusion, mandibular asymmetry, impaired masticatory function, and pain
      located to the affected joint or masticatory muscles were seen significantly more
      frequent in patients treated with closed reduction compared with those treated
      surgically (P = .005). Neither the degree of dislocation of the proximal
      fragment, concomitant mandibular fractures, nor the absence of posterior occlusal
      support seemed to influence the results.

PMID- 8133367
TI  - A fully visualized arthroscopic disc suturing technique.
AB  - Advanced arthroscopic procedures, including disc suturing, are advantageous in
      managing temporomandibular joint disorders. These techniques are indicated in
      cases of long-standing closed lock, displaced discs with reduction, and
      hypermobility with chronic dislocation. Disc suturing procedures can be done
      blindly, partially blindly, or fully visualized. Fully visualized suturing
      techniques have obvious advantages, but can be time-consuming, difficult to
      perform, and traumatic. This article presents a new suturing technique that is
      fully visualized and is less time-consuming and relatively easy to perform.

PMID- 8133368
TI  - Carbon dioxide laser excision and vaporization of nonplunging ranulas: a
      comparison of two treatment protocols.
AB  - A carbon dioxide laser in a defocused beam was used to vaporize four ranulas and
      four were treated by a combination of focused beam excision of the dome and
      vaporization of the wall and base. There was no recurrence in any patient at 6
      months and no complications were noted.

PMID- 8133369
TI  - Mandibular reconstruction with the Dacron urethane tray: a radiologic assessment
      of bone remodeling.
AB  - A retrospective study was made of 22 consecutive patients who underwent
      mandibular reconstruction with a Dacron (Osteo-mesh, Xomed Inc, Jacksonville, FL)
      tray technique from September 1988 to April 1992. Free autogenous iliac bone, in
      the form of particulate cancellous chips and marrow, was densely packed into the
      Dacron tray, that was adapted to bridge the mandibular segmental defect. Sixteen
      cases underwent uneventful healing with the formation of a continuous bony bridge
      and union with the remaining mandible. The pattern of bone remodeling and rate of
      resorption in these cases were assessed by sequential panoramic radiographs taken
      up to 3 years postoperatively. The mean horizontal dimension of the mandibular
      defects was 75 mm and the mean vertical reconstructed height was 25 mm. When the
      grafted bone was radiographically of uniform density, it progressed into a mature
      trabecular pattern matching that of the normal mandible. However, when there were
      areas of radiolucency, most likely from inadequate condensation of the graft,
      such areas were not replaced by bone in the long term. The bony height at both
      ends and the middle of the reconstructed segment underwent reasonably even
      resorption and retained about 80% of the bony height over a 3-year period. The
      rate of resorption was highest in the first 6 months and stabilized at about 2
      years. There were six failures, all showing significant irregular bony resorption
      prior to tray removal.

PMID- 8133370
TI  - Invasive oral aspergillosis in immunocompromised patients with leukemia.
AB  - The clinicopathologic characteristics of invasive oral aspergillosis in 16
      immunocompromised patients who developed this infection during antileukemic
      chemotherapy are described. The primary site of the infection was the marginal
      gingiva, there was severe spontaneous pain, and the patients developed spiking
      fever and granulocytopenia. Necrotic ulceration of the gingiva rapidly extended
      to the contiguous mucosa, muscle, and bone. Microscopically, the necrotic tissue
      contained thrombotic vascular infarcts and there were hyphae that showed frequent
      transverse septa and dichotomous branching. The invasive organisms were not
      responsive to amphotericin B in the absence of remission of the leukemia and
      restoration of the depressed host defenses. In 15 patients who showed improvement
      of hematologic status, oral aspergillosis was controlled by the combination of
      antifungal chemotherapy and debridement of necrotic tissues.

PMID- 8133371
TI  - Effect of freeze-dried poly-L-lactic acid discs mixed with bone morphogenetic
      protein on the healing of rat skull defects.
AB  - Porous poly-L-lactic-acid discs were prepared by a freeze-drying method (FDPLLA).
      During preparation of the discs, semipurified bone morphogenetic protein (BMP)
      was mixed with the poly-L-lactic acid (500 micrograms BMP per disc). The discs
      were implanted in the skull defects of rats and retrieved after 2 or 4 weeks.
      With the FDPLLA/BMP discs, new bone formation was observed at 2 weeks after
      implantation. On the other hand, plain FDPLLA discs failed to produce new bone
      formation even at 4 weeks after implantation. Calcium content of the retrieved
      FDPLLA/BMP discs was statistically higher than that of plain FDPLLA discs. These
      results suggest that FDPLLA may be an effective delivery system for BMP and that
      the FDPLLA/BMP disc may potentially have usefulness as a bone graft substitute.

PMID- 8133372
TI  - Stability of reconstituted methohexital sodium.
AB  - The purpose of this study was to determine the stability of reconstituted
      solutions of methohexital sodium over a 6-week period. Stability of methohexital
      was examined using reversed-phase high-performance liquid chromatography. The
      results indicate that reconstituted methohexital is extremely stable for up to 6
      weeks when stored at 4 degrees C. When stored at room temperature, reconstituted
      solutions of methohexital contained increasing levels of degradation products and
      showed a corresponding decrease in methohexital over a 6-week period. However,
      the rate of degradation of the drug was slow, with less than 10% of the
      methohexital undergoing breakdown. In addition, tests for microbial contamination
      of the solutions stored at room temperature and under refrigeration were negative
      for up to 6 weeks. This study demonstrates that methohexital, when stored under
      refrigeration for up to 6 weeks, is virtually chemically identical to a freshly
      reconstituted solution of the drug. When stored at room temperature, there is
      some degradation of the drug, but it is not known whether the small amount of
      degradation is clinically significant. This study emphasizes the importance of
      obtaining scientific data to support changes in guidelines related to handling
      and storage of drugs.

PMID- 8133373
TI  - Cefadroxil concentrations in human serum, gingiva, and mandibular bone following
      a single oral administration.
AB  - Cefadroxil concentrations in human serum, gingiva, and mandibular bone were
      measured by a paper disk method following a single 500-mg oral dose. The mean
      peak concentrations in serum, gingiva, and mandibular bone occurred at the
      identical time, 3 hours, and were 12.92 micrograms/mL, 6.50 micrograms/g, and
      2.67 micrograms/g, respectively. Mean cefadroxil concentration ratios of
      gingiva/serum and mandibular bone/serum at the peak time were 0.54 and 0.21,
      respectively. Mean concentrations in gingiva and mandibular bone at the peak time
      exceeded the minimum inhibitory concentrations for 90% of clinically isolated
      strains of a alpha-hemolytic streptococci.

PMID- 8133374
TI  - Submucosal nodule of the lower lip associated with pigmented neck macules.

PMID- 8133375
TI  - Nasolacrimal duct injury after Le Fort I osteotomy.

PMID- 8133376
TI  - Lipoma of the parotid gland: report of a case.

PMID- 8133377
TI  - Very-low-velocity gunshot wound to the facial structures: report of a case.

PMID- 8133378
TI  - Prevention of recurrent pathologic fracture of the atrophic mandible using
      inferior border grafting: report of two cases.

PMID- 8133379
TI  - Orthognathic surgery in a patient with Noonan's syndrome.

PMID- 8133380
TI  - The posterior zygomatic arch osteotomy to facilitate temporalis flap placement.

PMID- 8133381
TI  - Seek and you shall find.

PMID- 8133382
TI  - Setting the record straight.

PMID- 8133383
TI  - Social and functional impact of reduced posterior dental units in older adults.
AB  - The number of teeth needed to maintain adequate dental function in older adults
      is unknown. The purpose of this study was to examine the relationship between
      oral function and the number of opposing pairs of posterior teeth. We identified
      338 subjects with complete anterior dentitions from an interview and examination
      survey of Ontario adults aged 50 and over; 261 had no partial denture and 77 had
      removable partial dentures (RPD). Oral function was measured using questions
      assessing chewing ability, mandibular function and socio-psychological impact.
      Subjects with no partial dentures were further allocated to five groups, based on
      their dental status: complete dental arch (n = 69); 5-7 functional units-pairs of
      opposing posterior teeth (n = 109); 3 or 4 functional units (n = 48) and 0-2
      functional units (n = 35). Oral function problems increased with decreasing
      functional units being markedly more prevalent among the groups with 0-2
      functional units. 34% of subjects in the 0-2 group reported one or more problems
      with chewing ability compared to 6-17% in the other groups (chi 2 P = 0.001 d.f.
      = 3). The 77 subjects who wore removable partial dentures, reported social and
      dental function at levels comparable to those with no dentures. From these
      results, there appears to be little socio-functional need to replace lost
      posterior teeth with a partial denture unit the person has fewer than, 3
      posterior functional units. The low number of partial denture wearers limited our
      ability to detect a lasting benefit from RPD treatment.

PMID- 8133384
TI  - Processing dentures using a microwave technique.
AB  - In this research the technique of curing denture base acrylic resins by microwave
      energy was investigated with respect to polymerization method, hardness,
      mechanical and physical properties. Twenty-one different polymerization methods
      were used by varying radiation power and curing time. The Vickers hardness test
      was applied to the samples which were polymerized. The average value was found to
      be 22.46 VHN (Vicker hardness number), that is, almost the same as conventionally
      cured acrylic. The recommended polymerization method of curing acrylic was 3 min
      at 550 W in a microwave oven. Mechanical and physical tests were applied to the
      samples which were cured by the recommended polymerization method. The average
      transverse load to fracture value was found to be 7.6 kg, and the transverse
      deflection value was 1.5 mm at 3500 g, and 2.9 mm at 5000 g. Water sorption of
      acrylic resin cured by microwave energy was 0.72 mg cm-2 and the solubility rate
      in water was 0.038 mg cm-2. Results conformed with the ADA specification. The
      findings showed that acrylic resin cured by microwave energy is more resistant to
      mechanical failure than conventionally cured acrylic and this technique can
      safely be applied to the production of denture bases.

PMID- 8133385
TI  - Front tooth replacement with Tubingen (Frialit) implants.
AB  - 127 Tubingen (Frialit) implants have been clinically evaluated for a 10 year
      period. The implants were placed in the anterior region of the maxillae of 101
      patients to replace lost incisors, cuspids and premolars. Seventy-seven implants
      were placed within 3 months after loss of a natural anterior tooth, resulting in
      the preservation of the volume of the alveolar ridge and the contour of the
      surrounding soft tissues. This preservation of the volume of the alveolar ridge
      was due to the fact that the Tubingen implants have conical shapes and sizes,
      equal to those of the roots of natural teeth. The dentine-like colour and the
      biological properties of the bio-inert Al2O3 implant-material, in most of the
      cases was an advantage to the aesthetics of the prosthetic restorations and to
      the condition of the soft tissues in the permucosal area. The Tubingen implant is
      placed with a one-phase technique implying special care for the temporary
      restorations to avoid premature loading. Also prevention of overloading the
      ceramic material by the fixed restoration needs special attention in the
      construction of posts, cores and crowns. The overall survival-rate in this study
      with a mean follow-up of 4.5 years was 87%. Patient and dentist satisfaction was
      high.

PMID- 8133386
TI  - A technique for treatment of extensive periodontal defects: a case study.
AB  - This case study describes the use of oxidized cellulose mesh to improve healing
      of periodontal defects of poor regenerative capacity. Circumferential defects
      with horizontal bone loss were treated by surgical exposure of the root surface
      followed by scaling and root planing. Prior to flap replacement, oxidized
      cellulose mesh was positioned in incremental layers over the defects so as to
      replace the lost alveolar bone. It was to act also as a barrier to the ingress of
      epithelial cells and gingival fibroblasts into the healing wound using the
      principles vof guided tissue regeneration. Healing was good, with minimal post
      operative recession. Whether regeneration of alveolar bone and periodontal
      ligament occurred as a result of using this technique could not be determined in
      this clinical case study.

PMID- 8133387
TI  - Effect of a fatigue test and chewing training on masticatory muscles.
AB  - The effects of fatigue induced by 30 min of intense chewing before and after 4
      weeks of 1 h daily chewing training on masticatory muscles were studied in 15
      healthy subjects while eight subjects served as controls. EMG measurements in the
      postural position and during maximal clenching in the intercuspal position and
      clinical examination of the stomatognathic system were performed. Marked clinical
      signs of dysfunction were recorded after the first fatigue test. The severity of
      dysfunction diminished during the 4-week training period and was back at the
      baseline level at the end of it. In the second fatigue test, after the training
      period, the subjects developed less dysfunction. In the control group, a mainly
      stable pattern was found during the observation period. There was a great
      variation in EMG activity during the experimental period and there were no
      statistically significant changes observed between any of the recordings in any
      of the groups.

PMID- 8133388
TI  - Location of implants in the interforaminal region of the mandible and the
      consequences for the design of the superstructure.
AB  - The location and the number of implants to support an overdenture is of major
      importance for the superstructure design. Sometimes, jaw bone anatomy or
      posteriorly placed implants enforce the use of an angular bar to achieve a
      position above the alveolar ridge. Loads on such a bar may introduce a moment on
      the implants which can result in high bone stresses and eventually the loss of
      the implants. This study on stress distribution in the bone around the implants
      in an edentulous mandible was performed using a three-dimensional finite element
      model. One model with two implants placed just anteriorly of the mental foramen
      and connected with an anteriorly placed bar, following the curvature of the
      alveolar ridge, was compared with two other designs. First with a similar model
      but now without a bar and secondly with a model with four implants connected with
      straight bars. It is concluded that loading a bar, which is placed anteriorly of
      the interconnecting line between two implants, causes extremely large compressive
      and tensile stress concentrations in the bone around the implants. Therefore, in
      those cases, it is advised not to connect the implants or, in case a bar-clip
      attachment is preferred, to place additional implants in the frontal region.

PMID- 8133389
TI  - Dual cure luting composites--Part II: Clinically related properties.
AB  - Thirteen dual cure luting composites were compared in function of film thickness,
      consistency, and working time by using the American National Standard/American
      Dental Association (ANS/ADA) specifications for zinc phosphate cement and direct
      filling resins. The effect of temperature and setting reaction on the film
      thickness was also evaluated for some representative products. All three
      clinically related properties varied widely among the products investigated. A
      strong linear correlation was found between film thickness and consistency. This
      relation is supported by the temperature dependence of film thickness of dual
      cure luting composites. Cooling of the material increased the consistency,
      resulting in a larger film thickness, while heating reduced the film thickness
      because of the lower consistency. However, one product with a rather short
      working time at room temperature occasionally exhibited a dramatically enlarged
      film thickness after heating, probably caused by accelerated chemical
      polymerization. No correlation emerged between film thickness and maximum filler
      size or between consistency and filler weight content. Maximum filler size and
      filler weight content had been measured previously in Part I of this study.
      Scanning electron microscope (SEM) analysis of the cured film thickness samples
      revealed that the largest filler particles had been crushed under the heavy load
      pressure during film thickness measurement. The lack of correlation between
      consistency and filler weight content can be explained by the multifactorial
      determination of the consistency. It is concluded that the great diversity in the
      currently available luting composites makes clear specifications with regard to
      the optimum composition of luting composites urgently needed. Furthermore, more
      adequate methods for testing the film thickness of luting composites are also
      required.

PMID- 8133390
TI  - Masticatory electromyographic activity in healthy young adults and myogenous
      craniomandibular disorder patients.
AB  - The electromyographic (EMG) activity of the masseter and the anterior temporalis
      muscles were compared between 60 healthy controls and 61 myogenous
      craniomandibular disorder (CMD) patients. Subjects were asked to clench at 10%
      and at 50% of their maximum voluntary clenching level. The effects of CMD, age
      and gender were statistically analysed with the use of the analysis of
      covariance. The correlations between EMG asymmetries and the lateral slide from
      the retruded contact position to the intercuspal position and the asymmetry in
      the number of post-canine tooth contacts between the left and the right side were
      investigated. The CMD patients showed lower masseter EMG activities than the
      controls, whereas the anterior temporalis EMG activity was not different between
      the two groups. The activity index, relating the anterior temporalis EMG activity
      to the activity of the masseter muscles, confirmed the presence of a relatively
      high temporalis activity in the CMD group. No significant differences were found
      in the EMG asymmetries between the controls and the CMD patients. Males showed
      higher masticatory EMG activities than females. These gender effects were
      significant for the anterior temporalis at the 10% and 50% level and for the
      masseter muscle at the 10% level. The anterior temporalis EMG activity declined
      with age. No age related effects were observed in the masseter EMG. The lateral
      slide was larger and more prevalent in the CMD group. A significant correlation
      between the lateral slide and the anterior temporalis EMG was found for the CMD
      group at the 10% level. No correlation was found between the EMG asymmetry and
      the asymmetries in post-canine tooth contacts. IN CONCLUSION: significant CMD,
      age and gender effects were observed in the masticatory EMG activities of a group
      of myogenous CMD patients and a control group.

PMID- 8133391
TI  - Periodontal status of teeth in contact with denture in removable partial denture
      wearers.
AB  - The aims of the study were to determine the periodontal status of the teeth in
      contact with removable partial dentures (RPDs) and to compare them with other
      teeth in the opposing arch not related to any prosthesis. The periodontal status
      was also assessed in relation to the age of the dentures. Four hundred and twenty
      seven patients treated with RPDs from 1981 to 1986 were recalled for examination.
      Prior to prosthetic treatment they were given periodontal treatment and fillings
      when required. Initially all were given oral hygiene instructions and motivation.
      They were reviewed regularly only on a short-term basis. Eighteen patients were
      suitable for the present study comprising of eight males and 10 females whose
      mean age was 41 years. The RPDs were in use from 1.5 to 8 years (mean 4.6 years).
      The following parameters were assessed: Plaque index (P1I), Gingival index (GI),
      loss of attachment (LA) and tooth mobility. The wearing of RPDs resulted in
      higher P1I, GI and LA compared to the controls and these differences were
      statistically significant. There was an increased frequency of higher P1I, GI and
      LA with the increase in denture age. Minor changes in tooth mobility were
      observed. It was concluded that the wearing of RPDs was detrimental to
      periodontal health in patients whose oral hygiene was less than adequate.

PMID- 8133392
TI  - Surface texture evaluation of glass ionomer restorative materials polished
      utilizing poly(acrylic acid) gel.
AB  - This study evaluated the surface texture of three different glass ionomer
      restorative materials and a composite resin, polished by a new method using
      poly(acrylic acid) gel. Conventional polishing methods and finishing agents were
      compared to the proposed new procedure. Evaluations were carried out employing
      three techniques: profilometry, scanning electron microscopy and microhardness
      testing. The use of a poly(acrylic acid) gel with polishing discs gave
      significantly better results, and is therefore recommended for clinical
      applications.

PMID- 8133393
TI  - The effects of electrogalvanic stimulation therapy on masticatory muscle
      dysfunction as determined by the pantronic reproducibility index.
AB  - Patients with temporomandibular joint dysfunctional activity (TM dysfunction)
      present with a diverse spectrum of clinical signs and symptoms. The
      multifactorial aetiology of such disorders has been noted. Diagnostic and
      therapeutic problems arise due to the inadequacy of quantifying the dysfunction.
      TM dysfunction can affect the muscles of mastication which are responsible for
      mandibular movement. A pantographic reproducibility index (PRI) is available to
      quantitatively and qualitatively measure a subjects ability to reproduce
      mandibular border movements. Physical therapy modalities are used in the
      management of TM dysfunction. Electrogalvanic stimulation (EGS) is such an
      example. The effect of electrogalvanic stimulation on subjects with and without
      TM dysfunction was assessed by Pantronic PRI appraisal in 20 subjects. No
      statistically significant differences were noted. At the individual level, some
      changes were observed in susceptible subjects.

PMID- 8133394
TI  - The fibroblast growth factor and receptor multigene families.

PMID- 8133395
TI  - Progress in computer-generated three-dimensional reconstruction.

PMID- 8133396
TI  - DNA cytometric and interphase cytogenetic analyses of paraffin-embedded
      hydatidiform moles and hydropic abortions.
AB  - The combined application of DNA cytometric and interphase cytogenetic analyses
      was used to find objective criteria for the differential diagnosis of complete
      hydatidiform mole, partial hydatidiform mole and hydropic abortion. DNA ploidy
      and G0/G1 exceeding rates were determined using image and flow cytometric
      analyses on paraffin-embedded tissues of 166 cases: 71 cases of complete mole, 20
      cases of partial mole, and 75 cases of abortions. To determine the existence and
      histological distribution of cell subpopulations with numerical chromosome
      aberrations, interphase cytogenetic analysis using probes specific for
      chromosomes 1, X, and Y was applied to paraffin tissue sections of 23 cases: 12
      cases of complete mole, 3 cases of partial mole, and 8 cases of abortions. In
      contrast to previously reported findings that complete moles are diploid, the
      results of this study showed that complete moles are DNA-polyploid (96 per cent),
      with high G0/G1 exceeding rates and a high frequency of numerical chromosomal
      aberrations in the trophoblast hyperplasia. The majority of the partial moles
      were DNA-triploid (55 per cent). This study, however, also showed the presence of
      DNA-polyploid partial moles (30 per cent). Abortions were DNA-diploid (60 per
      cent) or DNA-triploid (39 per cent). DNA cytometric analysis, especially image
      DNA cytometric analysis with determination of the G0/G1 exceeding rate, and
      interphase cytogenetic analysis provide objective measurements which are
      contributory in the differential diagnosis between complete mole, partial mole,
      and hydropic abortion.

PMID- 8133397
TI  - T-cell lymphoma developing in Hodgkin's disease: evidence for two clones.
AB  - A case of peripheral T-cell lymphoma (PTL) occurring in a patient with Hodgkin's
      disease (HD) in relapse is described. The second neoplasm developed 25 months
      after the diagnosis of HD. Cytogenetic analysis on the lymph node biopsy at the
      time of diagnosis of PTL revealed the co-existence of two distinct, abnormal cell
      clones. The first clone was characterized by a reciprocal translocation
      t(5;7)(q13;q35) involving 7q35, namely the TCR-beta gene, as expected in T-cell
      lymphomas. The second cell clone carried trisomies for chromosomes 2, 5, 7, and
      14. By immunophenotypic and molecular analysis as well as by in situ
      hybridization, it was possible to prove that the malignant T-cells and the Reed
      Sternberg cells corresponded to different cell clones, one carrying the
      structural chromosome abnormalities and one carrying the numerical chromosome
      anomalies. These results indicate that the present case represented a true
      composite lymphoma.

PMID- 8133398
TI  - Diagnostic and prognostic significance of clonal T-cell receptor beta gene
      rearrangements in lymph nodes of patients with mycosis fungoides.
AB  - In this study, 25 involved and uninvolved lymph nodes from 22 patients with
      mycosis fungoides (MF) and seven dermatopathic lymph nodes from patients with
      benign skin disorders were studied for the presence of clonal T-cell receptor
      beta (TCR beta) gene rearrangements by Southern blot analysis. These results were
      correlated with the histological classification, follow-up data, and survival.
      The results of the histological classification and Southern blot analysis were
      concordant in 26 of 32 cases. Clonal TCR beta gene rearrangements were found in
      all six MF lymph nodes showing (partial) effacement of the normal lymph node
      architecture, but in none of the eight uninvolved dermatopathic MF lymph nodes
      and in none of the seven dermatopathic control lymph nodes. In addition, in 5 of
      11 dermatopathic MF lymph nodes that were considered to have early involvement by
      MF at histological examination, clonal TCR beta gene rearrangements were
      detected. In the group of MF patients with dermatopathic lymphadenopathy,
      patients with detectable clonal T-cell populations had a significantly shorter
      survival than patients without such a population (P < 0.01). The results of this
      study indicate that within the group of dermatopathic MF lymph nodes,
      prognostically different groups can be distinguished and that TCR beta gene
      rearrangement analysis may be an important adjunct in the early diagnosis of
      lymph node involvement by MF.

PMID- 8133399
TI  - Constant detection of surface and cytoplasmic immunoglobulin heavy and light
      chain expression in formalin-fixed and paraffin-embedded material.
AB  - The introduction of microwave detection systems has significantly enhanced the
      sensitivity of immunohistochemistry in formalin-fixed, paraffin-embedded tissue.
      The combination of protease digestion and microwave treatment including the use
      of heavy metal salts or urea gives an Ig heavy and light chain detection system
      in formalin-fixed and paraffin-embedded material as good as that achieved using
      fresh frozen material, with the advantage of a well-preserved morphology. The
      sensitivity of this method depends on the heavy metal salt used and its
      concentration. The use of urea yields equally sensitive results, while avoiding
      the toxicity of heavy metal salts. Heating times in the microwave oven also have
      an important influence on the results. The microwave-based technique may allow
      for the improved accessibility of formalin-masked antigens, as was shown here for
      cytoplasmic and surface immunoglobulins. It was demonstrated that formalin-fixed
      specimens of Burkitt's lymphoma when subjected to the new protocol almost always
      showed surface Ig expression, giving results comparable to those obtained in
      frozen sections. Moreover, it could be shown that in cases of B-chronic
      lymphocytic lymphoma (B-CLL) or immunocytoma, surface and cytoplasmic Ig could be
      detected, so that the difference may be just a quantitative one and thus may no
      longer be safely used as a criterion in differential diagnosis. In future, the
      wide use of this technique will allow for the study of Ig expression at the
      single cell level in morphologically well-preserved material.

PMID- 8133400
TI  - Expression of the c-erbB-3 protein in gastrointestinal tract tumours determined
      by monoclonal antibody RTJ1.
AB  - We have examined the expression of the c-erbB-3 protein in a wide range of
      tumours of the gastrointestinal (GI) tract using immunocytochemical staining. Two
      antibodies were employed, a polyclonal antibody, 49.3, and a new monoclonal
      antibody, RTJ1, both raised to a synthetic peptide from the cytoplasmic domain of
      the human c-erbB-3 protein. The antibodies recognize c-erbB-3 by
      immunoprecipitation and Western blotting of lysate prepared from a cell line
      engineered to overexpress the protein. Both antibodies also detect expression of
      the protein in formalin-fixed, paraffin-embedded human tissues. The RTJ1
      monoclonal antibody gave superior staining, showing lower background and more
      pronounced cell surface immunoreactivity. The c-erbB-3 protein was found in
      normal epithelial cells throughout the GI tract, in squamous epithelium of the
      oropharanyx and oesophagus, in the parietal cells of the stomach, and in the
      surface enterocytes of the small and large bowel. Seventy-six tumours arising at
      these sites were examined for c-erbB-3 protein expression. Widely varying levels
      of expression were seen, from absent to intense staining with cell membrane
      accentuation.

PMID- 8133401
TI  - Expression of p53 protein in normal, dysplastic, and malignant gastric mucosa: an
      immunohistochemical study.
AB  - Mutations in the p53 nuclear oncogene are the most frequent genetic abnormalities
      encountered in human malignancies. Using the polyclonal antibody CM-1, we have
      examined the expression of the p53 oncoprotein immunohistochemically in archival
      material of normal, dysplastic, and malignant gastric mucosa. Abnormal expression
      of this protein was not observed in biopsies of normal gastric tissue (n = 30)
      but was detected in 22 of the 36 gastric cancers analysed (61 per cent). Nuclear
      staining was diffuse in 15 of the positive cancer cases, the remaining seven
      showing a more varied heterogeneous staining pattern. Abnormal p53 protein was
      not detected in mild (n = 14) or moderate (n = 16) gastric dysplasia but was
      present in 3 out of 15 severe dysplasia cases. The results suggest that
      expression of the p53 oncoprotein is a common finding in gastric cancer and
      occurs as a late event in the malignant transformation process.

PMID- 8133402
TI  - Patterns and composition of basement membranes in colon adenomas and
      adenocarcinomas.
AB  - We studied the distribution of type IV collagen and type VII collagen in the
      basement membranes of normal mucosa of the colon, adenomas, and adenocarcinomas
      using immunoperoxidase and immunofluorescence techniques. In normal mucosa, we
      found regular type IV collagen-positive basement membranes, lining vascular
      structures and mucosal epithelia. These basement membranes, however, lacked type
      VII collagen. In adenomas of the colon, intact basement membranes were observed
      through type IV collagen staining. Type VII collagen staining was also detected,
      but only in connection with dysplastic epithelium. Adjacent to the dysplastic
      epithelium in adenomas, histologically normal epithelium also showed type VII
      collagen staining along the basement membrane, but this was restricted to the
      epithelium of the luminal surface. These areas were also investigated for
      expression of keratins 8, 18, and 19, and keratins 5 and 8 (monoclonal antibodies
      NCL-5D3 and RCK 102, respectively), but altered differentiation was not detected
      using this technique. In adenocarcinomas of the colon, type IV collagen was
      irregularly deposited in the basement membrane of neoplastic tubules. Type VII
      collagen staining was detected only in well or moderately differentiated
      carcinomas and in higher amounts. Our findings therefore reveal a transient
      expression of type VII collagen in the transition of dysplastic epithelium into
      carcinoma, suggesting the involvement of type VII collagen in the process of
      early invasion.

PMID- 8133403
TI  - Synthesis and degradation of basement membranes in benign and malignant salivary
      gland tumours. A study by in situ hybridization.
AB  - In this study we investigated the mRNA expressions of 72 kD and 92 kD type IV
      collagenases, alpha 1(IV) chain of type IV collagen, and laminin B1 chain mRNAs
      in a set of malignant and benign salivary gland tumours and compared the results
      with non-neoplastic salivary gland tissue. While only a few cases expressed 72 kD
      type IV collagenase mRNA or alpha 1(IV) chain of type IV collagen mRNA in tumour
      cells, 92 kD type IV collagenase and laminin mRNA synthesis could be seen in the
      neoplastic cells of many tumours. Stromal fibroblasts or endothelial cells
      demonstrated mRNA synthesis for all these proteins to a variable degree except
      for Warthin's tumours, in which no synthetic activity for any of the proteins
      could be seen. Since signals for 92 kD type IV collagenase mRNA could be seen in
      non-neoplastic epithelial cells of the salivary gland, the synthesis of 92 kD
      type IV collagenase by tumour cells can be regarded as an intrinsic property of
      salivary gland epithelial cells. The pattern of mRNA synthesis for 72 kD and 92
      kD type IV collagenases follows that observed in other tumours, in which the
      stromal cells also mainly synthesize 72 kD type IV collagenase while epithelial
      tumour cells more readily express 92 kD type IV collagenase mRNA. The synthesis
      of type IV collagenases by malignant tumours has been suggested to be of crucial
      importance for invasion and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133404
TI  - The specificity of integrin-ligand interactions in cultured human renal
      epithelium.
AB  - Members of the beta 1 integrin family are present at the basolateral membrane of
      human renal tubular epithelium in vivo and at the ventral surfaces of cultured
      renal epithelial cells, at the sites appropriate for cell substratum adhesion. In
      this study we have proven that these molecules are indeed functional in mediating
      cell substratum attachment in normal human renal epithelium by using monoclonal
      antibodies to integrin alpha subunits to block initial cell attachment. The
      importance of arginine-glycine-aspartic acid (RGD) recognition by cell surface
      receptors in various extracellular ligands was also examined using synthetic
      peptides. RGDS peptide strongly inhibited attachment to plain plastic or
      fibronectin-coated substrata but had no effect on cell adhesion to laminin-coated
      coverslips.

PMID- 8133405
TI  - Trabecular bone does not have a fractal structure on light microscopic
      examination.
AB  - The fractal dimension of the boundary of trabecular bone in 62 biopsies was
      measured on histological sections using a box-counting method implemented on a
      microcomputer image analysis system. The calculated fractal dimension had a mean
      value of 0.99 with a normal distribution. Since this value is not greater than
      the topological dimension, trabecular bone, when examined by light microscopy,
      does not have a fractal structure. Conventional Euclidean dimensions will
      continue to be the most useful measurements in bone histomorphometry.

PMID- 8133406
TI  - Immunohistochemical identification of leucocyte populations in normal tissue and
      inflamed synovium of the rabbit.
AB  - A panel of monoclonal antibodies which recognizes well-defined markers of rabbit
      leucocytes has been used in an immunohistochemical survey of normal rabbit
      spleen, thymus, and liver, and of inflamed synovial tissue. The results
      demonstrate that these antibodies are well suited for the identification of
      leucocytes in frozen sections of rabbit tissues and that T lymphocytes,
      macrophages, and neutrophils can be readily distinguished. Antibodies to CD44
      differentiate between medullary and cortical thymocytes, with the cortical cells
      being almost entirely negative for this marker. Antibodies to RLA class II show
      that periportal lymphocytes in the liver express RLA-DR but not RLA-DQ. The type
      A cells of the synovial lining from inflamed joint tissue are stained by
      antibodies that recognize macrophages in a manner similar to that found in the
      human synovial lining.

PMID- 8133407
TI  - Cardiovascular pathology.

PMID- 8133408
TI  - Psychosis as a mode of exitus in a cancer patient.

PMID- 8133409
TI  - Music therapy in pain and symptom management.
AB  - The use of music therapy in pain and symptom management in the care of patients
      with long-term and life-threatening illnesses can be an effective non
      pharmacologic approach to help ameliorate pain and suffering. By altering
      affective, cognitive, and sensory processes, music may decrease pain perception
      by distraction, change in mood, increased control, use of prior skills, and
      relaxation. This article reviews the background of the use of music therapy in
      pain management, explores a theoretical framework, and describes methods and
      techniques. Three case studies are provided to demonstrate the work.

PMID- 8133410
TI  - The prevention of localized ridge deformities using guided tissue regeneration.
AB  - Healing of extraction sockets where the buccal plate of bone has been destroyed
      often results in localized ridge deformities. This is most likely due to the
      ingrowth of extraskeletal connective tissue into the space originally occupied by
      the tooth which then fills with a combination of bone and soft tissue. Techniques
      for managing these defects have been described, but it would be preferable to
      prevent them from occurring at all. Using the principles of guided tissue
      regeneration, a surgical technique is described that can be applied to post
      extraction sites that are deficient in alveolar bone thereby preventing localized
      ridge deformities. Representative cases are presented illustrating the technique.

PMID- 8133411
TI  - The distribution and transmission of Actinobacillus actinomycetemcomitans in
      families with established adult periodontitis.
AB  - The prevalence and genotype distribution of Actinobacillus actinomycetemcomitans
      strains in families where at least one adult family member (proband) suffered
      from periodontal disease was investigated to better understand how this
      periodontal organism is acquired or transmitted. Fifteen probands with severe
      (established) periodontal disease (EPD) and their 46 immediate family members
      were sampled for A. actinomycetemcomitans. Among the 15 families, 10 contained at
      least one additional family member colonized with oral A. actinomycetemcomitans.
      Genomic DNA from 3 subgingival A. actinomycetemcomitans strains from each of the
      10 probands and their 17 family members were amplified and characterized by the
      polymerase chain reaction (PCR) using a single arbitrary primer known to
      distinguish A. actinomycetemcomitans strains. The PCR products from each strain
      were separated by electrophoresis on a 1% submarine agarose gel containing
      ethidium bromide and visualized by UV light transillumination. The amplification
      products migrated to form readily distinguishable bands and, since the banding
      patterns were characteristic of strains of A. actinomycetemcomitans, these
      patterns were called "amplitypes." The culture studies showed that 51% of all
      patients suffering from EPD carried oral A. actinomycetemcomitans. Moreover, 50%
      of their spouses and 30% of their children harbored the bacterium. Comparison of
      the PCR-generated amplitypes showed that 26 out of 27 individuals had strains
      exhibiting a single amplitype of A. actinomycetemcomitans, the 27th being
      colonized by 2 different amplitypes. They also showed that in 6 out of 7
      families, the husband and wife did not harbor the same A. actinomycetemcomitans
      amplitype. Furthermore, most often children carried an an amplitype identical to
      one of the parents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133412
TI  - The influence of molar furcation involvement and mobility on future clinical
      periodontal attachment loss.
AB  - The purpose of this study was to determine the influence of furcation involvement
      (FI) and mobility (MO) on change in probing periodontal attachment level (AL) on
      molar teeth. Twenty-four patients were selected from The University of Michigan
      longitudinal periodontal clinical trial. The patients who met the entry criteria
      received a baseline examination and were treated by periodontal scaling and root
      planing followed by different periodontal surgical approaches in a split-mouth
      design. Patients were placed on a 3-month interval for maintenance prophylaxis
      and had yearly periodontal scorings for a period of 8 years. The scorings
      included determination of AL, FI, MO, and tooth loss (TL). Data for molar teeth
      from three different time periods (at entry (A) and at 1 (B) and 8 (C) years)
      were analyzed. The results demonstrated that teeth with FI were 2.54 times more
      likely to be lost when compared to teeth without FI during the maintenance
      period. By using paired t test approach to the probing attachment level data,
      molars with FI had significantly more loss between times B and C but not between
      A and B or A and C. Teeth with increased MO demonstrated significantly more AL
      between times A and C and B and C. When the interaction between MO and FI was
      analyzed, teeth with both FI and MO had significantly more attachment loss during
      the maintenance period (B to C). No statistically significant difference was
      found among the three different therapeutic approaches (pocket elimination,
      curettage, and modified Widman flap) during any of the time periods.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8133413
TI  - Short-term microbiological and clinical effects of subgingival irrigation with an
      antimicrobial mouthrinse.
AB  - Fifty chronic adult periodontitis patients completed a 6-week controlled, double
      blind, split mouth clinical study to determine the effects of subgingival
      irrigation with an antimicrobial mouthrinse on periodontal microflora,
      supragingival plaque, and gingivitis when used as an adjunct to normal oral
      hygiene. Qualifying subjects had at least four sites, two on each side of the
      mouth, with probing depths between 4 and 6 mm, which bled on gentle probing.
      Following baseline examinations, subjects received a half mouth scaling and
      prophylaxis and full mouth subgingival irrigation with either the antimicrobial
      mouthrinse or sterile colored water control professionally delivered. Subjects
      continued irrigation at home once daily for 42 days with their assigned rinse
      delivered via a subgingival delivery system. All sites in the mouth were scored
      at baseline and at day 42 for supragingival plaque, bleeding on probing, and
      redness. For the four selected periodontitis sites, probing depth and attachment
      level were measured at baseline and on day 42; additionally, supragingival plaque
      and gingival redness were scored on days 7 and 21. Subgingival plaque samples for
      microbiological analysis were harvested from the selected periodontal sites at
      baseline and on days 7, 21, and 42. Microbiologically, irrigation with the
      antimicrobial mouthrinse resulted in statistically significant reductions
      compared to control in putative periodontopathogens, including black pigmenting
      species, which persisted at 42 days. Clinically, subgingival irrigation with the
      antimicrobial mouthrinse produced a significant reduction in supragingival plaque
      (P < 0.001), bleeding on probing (P = 0.019), and redness (P = 0.017) compared to
      the control, whether or not the area irrigated received a prophylaxis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8133414
TI  - Relationship of oral malodor to periodontitis: evidence of independence in
      discrete subpopulations.
AB  - Associations between oral malodor, measures of periodontal disease, and trypsin
      like activity of periodontal pathogens on tongue and teeth were examined in 127
      subjects. Volatile sulphur compound (VSC) measurements were made with a portable
      sulphide monitor; oral malodor was also estimated by organoleptic methods.
      Measurements repeated one week apart indicated that steady-state VSC levels (r =
      0.72; P = 0.0001) and peak VSC levels (r = 0.63; P = 0.0001) were reproducible
      but these r values were not significantly different (P > 0.1). There was a
      significant correlation between tongue odor and peak VSC levels (r = 0.40; P =
      0.0001) and between tongue odor and whole mouth organoleptic measures (r = 0.55;
      P = 0.0001). To study the effect of reducing microbial colonization on oral
      malodor, chlorhexidine gluconate (0.2%) rinsing was prescribed for 7 days.
      Reductions of VSC levels were significant for both peak (37%) and steady-state
      (41%) data (P = 0.0001). Anaerobic periodontal pathogens on the tongue estimated
      by the proportions of positive BANA tests were reduced 19% (P = 0.001) and this
      was concomitant with a 40% (P = 0.0001) decrease in organoleptic measurement of
      the tongue dorsum. Mean pH measurements of the tongue dorsum showed large
      reductions from 6.9 initially to 6.3 post-treatment (P = 0.0001). Subjects were
      divided into periodontitis/no periodontitis based on periodontal inflammation and
      probing depth (> or = 5 mm). Of the 37 subjects with periodontitis, 23 had oral
      malodor whereas 52 out of 90 periodontally healthy subjects exhibited malodor.
      Chi square analysis comparing halitosis in subjects with and without
      periodontitis showed no statistically significant association (chi 2 = 0.208; P
      0.65) between these two factors although the intensity of malodor as based on VSC
      concentration in periodontally healthy subjects was 19% less (mean = 111 ppb)
      than in subjects with periodontitis (mean = 136 ppb). The odds ratio was 1.2,
      indicating that oral malodor was not associated with periodontitis. These data
      indicate that a large proportion of individuals with oral malodor are
      periodontally healthy and that the mucosal surface of the tongue is a major site
      of oral malodor production.

PMID- 8133415
TI  - Detection of Porphyromonas gingivalis in gingival exudate by a dipeptide-enhanced
      trypsin-like activity.
AB  - Porphyromonas gingivalis in subgingival plaque is an important risk factor for
      future periodontal attachment loss in susceptible adults. The elimination of P.
      gingivalis is usually concomitant with a healing process. Therefore, it should be
      valuable to have an easy chairside method to follow the effect of periodontal
      treatment on P. gingivalis detection as well as on its eventual reappearance
      during the maintenance period. We have previously reported the stimulation of
      amidolytic activity of P. gingivalis by the addition of glycyl-glycine to the
      assay buffer. In this study we determined the proportions of P. gingivalis,
      Prevotella intermedia, Actinobacillus actinomycetemcomitans, Fusobacterium
      nucleatum, Capnocytophaga spp, Campylobacter rectus, and Eikenella corrodens by
      cultivation technique and the amidolytic activity, using N-benzoyl-L-arginine-p
      nitroanilide (BAPNA) as substrate, in gingival exudate before and during a 3-year
      treatment and maintenance period. P. gingivalis was the only species yielding a
      high and persistent correlation to stimulated amidolytic activity (P values < or
      = 0.0001) on both site (r = 0.5) and subject (r = 0.8) level. Testing pure
      cultures of suggested periodontal pathogens for effect of glycyl-glycine on
      amidolytic activity, we found that of P. gingivalis to be 5.9-fold increased. The
      amidolytic activity of Treponema denticola was only slightly stimulated (ratio
      with/without glycyl-glycine = 1.2) and that of Capnocytophaga slightly inhibited
      (ratio with/without glycyl-glycine = 0.8). The outcome of this study has the
      potential to be used for the development of a simple, rapid, and inexpensive
      assay for a qualitative and quantitative determination of P. gingivalis in
      gingival crevicular fluid.

PMID- 8133416
TI  - Evaluation of a simple modified radiographic alignment system for routine use.
AB  - Radiographic frames used for longitudinal studies may be in part unreadable for
      measuring crestal bone change. Sites may not be present on the film, or the
      measurement reliability may be compromised because of dissimilar geometry.
      Several techniques used to address this problem are expensive, time-consuming,
      and required great skill. For the present study a commercially-available
      alignment system was simply modified by addition of a reference pin in the bite
      block, facilitating the repositioning of the film holder for a second exposure.
      This study determined the ability of the modified instrument to: 1) improve the
      geometrical correspondence between serial radiographs; and 2) reduce the
      frequency of missed sites in the film. Two pairs of x-rays were taken for each of
      40 subjects, 1 pair with the standard alignment instrument of an assigned site
      and 1 pair with the modified instrument of the contralateral site. Measurements
      of alveolar bone height were performed using the "side by side" technique. The
      modified instrument yielded significantly smaller measurement differences and a
      significantly better geometrical correspondence than the conventional system (P <
      0.05). Also, the modified instrument yielded significantly greater (P < 0.01)
      readable sites (86%) as compared to the conventional instrument (62%). The simply
      modified instrument facilitates the correct interpretation of serial radiographs.

PMID- 8133417
TI  - Modeling the relationship between clinical, microbiologic, and immunologic
      parameters and alveolar bone levels in an elderly population.
AB  - A cross-sectional periodontal study of 74 subjects aged 65 to 75 years was
      performed. Clinical data were collected and related to microbiological and
      immunological data. A statistical model (step-wise multiple regression) of
      factors related to bone loss was created initially using clinical data only; then
      by adding either the microbiologic or immunologic data; and then by using
      clinical, microbiologic, and immunologic data together. When only clinical data
      were considered, three factors were found to have significant positive
      correlations with bone loss. Tooth mobility accounted for 17% of the variability
      in the alveolar bone level measurements, probing depth for 12%(r2), and plaque
      index for 3%, for a total of 32% of the variability explained by these clinical
      factors. Tooth mobility and probing depth were clinical factors which remained
      significant in the model when the microbiological data were also considered. As
      percentages of the total cultivable microbiota, E. corrodens (r2 = 14%) and black
      pigmenting Prevotella intermedia (r2 = 4%) correlated positively with alveolar
      bone loss. The addition of the microbiologic data only increased the r2 to 33%.
      When immunological data were considered with the clinical data, pocket depth and
      tooth mobility were the clinical parameters which remained in the model. IgG
      antibody levels to P. gingivalis W83 and/or 381 (r2 = 24%) A.
      actinomycetemcomitans 627 (r2 = 2%) were the significant immunologic measures
      having a positive correlation with bone loss. Anti-F. nucleatum levels had a
      significant negative correlation. A total of 50% of the variability in alveolar
      bone level was accounted for in the model by the addition of specific serum
      antibody levels to subgingival plaque microorganisms. When clinical,
      microbiological, and immunological measurements were all considered together,
      antibody to P. gingivalis W83 and/or 381 (r2 = 42%), percentage of B-lymphocytes
      (r2 = 3%), probing depth (r2 = 4%), anti-E. corrodens levels (r2 = 2%), and anti
      P. gingivalis 33277 levels (r2 = 4%) all had significant positive correlation
      with loss of alveolar bone. The number of enteric bacteria, anti-F. nucleatum
      levels, and anti-P. intermedia levels each had a significant negative correlation
      with alveolar bone heights. The r2 for this model was 75%. These results
      indicated that antibody levels to subgingival plaque microorganisms and tooth
      mobility were the best predictors of bone loss in the elderly patients tested in
      this study.

PMID- 8133418
TI  - Regional accelerated phenomenon in the mandible following mucoperiosteal flap
      surgery.
AB  - Striking remodeling activity occurs adjacent to the site of injury in orthopedic
      surgery. This reaction has been described as regional accelerated phenomenon
      (RAP), as it speeds up the healing stage. The phenomenon is a transient burst of
      localized remodeling process following surgical wounding of cortical bone. We
      explored whether RAP occurs following mucoperiosteal flap surgery in the jaw
      bone. Mucoperiosteal flaps were performed on 60 Wistar rats, either only on the
      buccal aspect or both on buccal and lingual aspects of the mandible. The surgical
      procedure lasted an average of 30 seconds and the flap was readapted without
      sutures. The rats were sacrificed at 3, 7, 10, 14, 21, and 120 days. High
      resolution x-ray microradiography of 1 to 1.5 mm thick ground sections between
      premolar and molar regions of the mandible were analyzed and revealed large areas
      of radiolucency which correlated to massive resorption of the alveolar bone, as
      well as areas in the bone proper. The RAP was observed as early as 10 days in the
      treated side group. Striking resorption of the cortical bone, both on the surface
      and the bone proper, occurred on the periodontal aspect of the crestal bone
      leading to widening of the periodontal ligament space, where a mucoperiosteal
      flap was performed on the buccal aspect. The resorption was more prominent when a
      mucoperiosteal flap was performed both on the lingual and buccal aspect. The
      alveolar bone recovered almost to control levels 120 days after surgery.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8133419
TI  - Host responses in patients with generalized refractory periodontitis.
AB  - Although patients with refractory periodontitis have been widely reported, no
      clear biologic profile of these patients has been noted. The purpose of the
      present study was to evaluate host responsiveness of a well-defined group of
      refractory periodontitis patients by determining the effect of a
      lipopolysaccharide (LPS) challenge on monocyte surface receptor density and on
      the release of inflammatory mediators. Venous blood was obtained from 7
      refractory periodontitis, 8 stable periodontal maintenance, and 8 gingivitis
      patients with no evidence of periodontitis. Mononuclear cells were cultured in
      either control media or media treated with Actinobacillus actinomycetemcomitans
      (Aa), Porphyromonas gingivalis (Pg), or Salmonella typhimurium (S. typh) LPS. At
      0 and 24 hours supernatants were assayed for prostaglandin-E2 (PGE2) and
      interleukin-1 beta (Il-1 beta) release by ELISA. Using flow cytometry the density
      of specific monocyte surface receptors were assayed with Mo3e and LeuM3
      monoclonal antibodies (mAb); T-cell CD4/CD8 ratios were assayed with OKT-3, OKT
      4, and OKT-8 mAb. After 24 hours incubation with Pg or S. typh LPS, the
      upregulation of the Mo3e receptor was significantly decreased for refractory
      periodontitis patients (P < 0.05) when compared to gingivitis and to stable
      maintenance patients. In refractory periodontitis patients the T-cell CD4/CD8
      ratio was decreased. Upon stimulation with Pg or S. typh LPS, monocytes from
      stable maintenance and refractory periodontitis patients released more Il-1 beta
      (P < 0.05) and PGE2 (P = 0.13 and 0.15) than monocytes from gingivitis
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133420
TI  - A histomorphometric study on the healing of class III furcations utilizing bone
      labelling in beagle dogs.
AB  - The dynamics of bone turnover in the furcations of teeth treated with expanded
      polytetrafluoroethylene (ePTFE) membranes were evaluated using multiple
      fluorochrome labels in 6 male beagle dogs. Loss of attachment involving the
      furcation area was induced in the second, third, and fourth premolar teeth using
      silk ligatures. The resulting defects were treated with the use of mucoperiosteal
      flaps for access, debridement of the defects, and placement of ePTFE membranes
      covering the furcations of the second and fourth premolars (experimental teeth)
      while the third premolar received only debridement without membrane placement
      (control tooth). Five fluorochrome labels were administered intravenously at
      timed intervals to act as markers of the osseous response. Membranes were removed
      at 4 weeks and all animals were terminated at 12 weeks post-membrane placement.
      One side of the mandible was decalcified, sectioned at 7 microns, and stained
      with either hematoxylin and eosin or Gomori's tri-chrome. The opposite side
      provided non-decalcified tissue processed as 100 microns ground sections. Using
      fluorescent light and point-hit evaluation, tissue in the coronal half of each
      specimen was classified as either labelled bone, unlabelled bone, or resorption
      space. In addition, microradiographs were prepared of each ground section and
      specimens classified as either woven bone, old lamellar bone, or new lamellar
      bone. No significant differences in attachment levels, or level of junctional
      epithelium, were observed in decalcified sections although greater remodeling
      activity was noted in the experimental specimens. Comparison of ground sections
      revealed significant differences (P < 0.05) in all categories with both methods
      of evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133421
TI  - Osteosarcoma presenting as supracrestal bone formation.
AB  - We report an unusual case of maxillary osteosarcoma presenting as supracrestal
      bone formation in a 41-year-old woman. This case is of interest from the point of
      view of radiographic appearance of supracrestal bone formation with widened
      periodontal ligaments and the buccal and palatal swelling of the tissues.
      Moreover, to the best of our knowledge, the histopathologic evidence of cemental
      resorption has not been reported earlier.

PMID- 8133422
TI  - [Emulsion systems. I. Comparison of different formulation methods].
AB  - This paper examines different technics of emulsifying systems formulation: those
      using the research of HLBc and those using the phase diagram. The comparison of
      these two methods of formulation permits us to describe one method looking for
      the HLBc of each proportions of the phase diagram. So a volume is determined
      allowing to choose more securely the surfactants proportions and also to end on
      surer formulation.

PMID- 8133423
TI  - [Oral freeze-dried forms of procyanidins].
AB  - Oral freeze-dried forms based on procyanidins were prepared. Effort was focused
      on the choice of the binder and the determination of the optimal conditions of
      freeze-drying.

PMID- 8133424
TI  - [Methodologic study of the stability of intravenous nutritive emulsions].
AB  - Stability studies are one of the main steps of emulsion development, since
      emulsions are thermodynamically unstable systems. This is even more critical for
      drugs, and especially for nutritive parenteral emulsions considering the large
      volumes which are infused to patients. Physico-chemical stability of emulsions
      can be estimated, either under real storage conditions, or using accelerated
      testing that are of great interest in formulation. After a literature review of
      stability testing applied to emulsions, we give an example of procedure which is
      especially useful for intravenous nutritive emulsions.

PMID- 8133425
TI  - [Effects of the monosaccharide derivative 8RN-DAGal on the putative P-type
      calcium channel expressed in Xenopus oocytes].
AB  - P-type calcium channels are expressed in Xenopus oocytes after injection of rat
      cerebellar mRNA. The FTX and omega-Aga-IVa toxins extracted from Agelenopsis
      aperta venom are known to inhibit the activity of this channel. The present
      results demonstrate that 8RN-DAGal is also a antagonist of P-type calcium
      channels. The inhibition of the current, obtained with Ba2+, as charge carrier,
      is voltage dependent.

PMID- 8133426
TI  - [Use of a dynamometer in hospital pharmacy. Its use to study the mechanical
      properties of plastic materials].
AB  - The stretching test is in current use in Pharmaceutical Industry to characterize
      the mechanical properties of materials or to control medical devices such as
      catheters. Given the lack of official standards in the French Pharmacopee, we
      present here the results of an experiment carried out in Hospital Pharmacy. The
      value of the results will be depending on the manual gesture of the operator and
      on the experimental conditions for a given material. The factors which appear to
      be essential are the following: numerous samples, necessary to assess a good
      repeatability, the stretching speed and the place of the rupture that have to be
      defined, so as the manual fixation of the samples. This test is interesting in
      Hospital Pharmacy but the methodology remains a problem so that it cannot be
      recommended for an occasional use, in spite of an apparent simplicity.

PMID- 8133427
TI  - Pulse radiolysis study of the reactivity of chloramphenicol, diazepam and
      clonazepam with the electron and the hydroxyl radical.
AB  - Chloramphenicol (CAP), diazepam (DIAZ) and clonazepam (CLONA) have been
      irradiated in aqueous and methanolic solutions by pulsed electrons (Febetron
      707). Spectra of the species formed by the attack of the solvated electron and of
      OH radical have been determined. The kinetics of reaction of CAP, DIAZ, and CLONA
      with the solvated electron have been measured. Reactions of radical-radical
      recombination have also been studied. All these reactions are limited by the
      diffusion of the reactive species.

PMID- 8133428
TI  - Accelerated stability of Ibuprofen-Eudragit RSPM sustained release tablets, IR
      and DSC solid stability testing.
AB  - Preformulated Ibuprofen-Eudragit RSPM sustained release tablets were subjected to
      accelerated stability testing at 25, 37 and 45 degrees C for 6 months. The stored
      tablets were evaluated for the intact drug in the formula, drug-polymer
      interaction and compatibility of the drug with the formulated excipients using
      infra red spectroscopy (IR) and differential scanning calorimetry (DSC). The IR
      spectrum of Ibuprofen in the tablets prepared by 15% w/v Eudragit RSPM as a
      granulating agent and containing 23% w/v Avicel pH 102 as an excipient is similar
      to the IR of standard Ibuprofen. There is no change in the IR spectra of the
      tablet components before and after storage of those tablets at the different
      investigated temperatures for 1, 3 and 6 months. The DSC thermograms of the
      Ibuprofen stored tablets show that the drug was still in the highly pure (> 98%)
      crystalline form and there was no significant degradation after storage
      indicating the stability of the drug on storage. In detecting Ibuprofen purity in
      the stored tablets, plotting of the sample temperature versus the reciprocal of
      the fraction of Ibuprofen melted showed deviation from Van 't Hoff linear plot.

PMID- 8133429
TI  - [Sumatriptan in clinical practice].

PMID- 8133430
TI  - [Present and future choice of pharmaceutical forms for intravaginal
      administration. II. Barrier systems and vaginal rings].
AB  - In part I of this review, various vaginal products for local and systemic
      treatment have been described and discussed. Part II is reserved to other
      intravaginal contraceptive systems. Some devices as diaphragms, sponges, ... have
      a mechanical contraceptive advantage associated or not with a spermicidal
      activity and can or cannot protect against venereal diseases. Other devices like
      intravaginal rings allow a long-acting and controlled release of contraceptive
      hormones and it is quite possible that they replace orale contraceptive dosage
      forms. Various approaches in designs, safety, effectiveness, inconvenience and
      advantages are discussed.

PMID- 8133431
TI  - [Reactions and interactions of drugs].

PMID- 8133432
TI  - Injury: our children's greatest health problem.

PMID- 8133433
TI  - Caring for a chronically ill infant: a paradigm case of maternal rehearsal in the
      neonatal intensive care unit.
AB  - This study examines a mother's perspective of caring for a chronically ill infant
      coming home from the neonatal intensive care unit. Understanding the meaning of
      the situation for the parent can foster excellence in clinical practice that is
      based on understanding derived from descriptions of their experience. This paper
      presents a paradigm case extracted from a larger phenomenological study that is
      examining the high-risk perinatal experience. Hermeneutic methods used for
      analysis led to the discovery of five meanings in the experience for the parent:
      (a) uncertainty; (b) experiencing the baby as powerful; (c) striving to gain
      acceptance from the baby; (d) blurred territory in taking up the practices of
      care; and (e) being alone and vulnerable.

PMID- 8133434
TI  - Parents' perceptions of diabetes in adolescent daughters and its impact on the
      family.
AB  - Parent's perceptions of diabetes in adolescent daughters and its impact on the
      family was examined. Transitions in health and developmental state affect the
      experience of families and the ability to make needed adjustments. Adjustments in
      the parental subsystem are required at adolescence to promote increased
      independence. Qualitative content analysis of semistructured parent interviews
      showed that the daughter's diabetes was perceived to draw the whole family closer
      together while negatively affecting the spousal relationship. Episodes of poor
      diabetic control were experienced or anticipated in relation to adolescence.
      Suffering emotional distress was a central process related to parental concerns
      about diabetic control.

PMID- 8133435
TI  - Nature and prevalence of ribavirin aerosol administration in U.S. pediatric
      hospitals.
AB  - A survey was undertaken to determine the nature and prevalence of ribavirin
      aerosol administration in pediatric hospitals. Ribavirin was administered in
      79.4% of the respondents' hospitals. The majority used head hoods for aerosol
      administration. Ventilators were the primary method used by 6% of the
      respondents. This study demonstrates typical types of ribavirin exposure and the
      need to evaluate effects of chronic exposure.

PMID- 8133436
TI  - Parental sensitivity to infant cues: similarities and differences between mothers
      and fathers.
AB  - This study investigated the relationship of parent and infant characteristics to
      parental sensitivity to infant cues. Thirty-two families with firstborn infants
      were observed in a play situation. Capacity for empathy was the best predictor of
      sensitivity to infant cues for both mothers and fathers. Attitudes toward infant
      care also predicted sensitivity in mothers but not fathers, whereas nonverbal
      decoding ability, marital adjustment, baby temperament, and gender were unrelated
      to sensitivity to cues. Significant differences were found between parents in
      terms of their capacity for empathy and attitudes toward infants. Compared with
      fathers, mothers were both more empathic and had more positive attitudes than
      fathers.

PMID- 8133437
TI  - Developing and implementing a bereavement program for a children's hospital.
AB  - The grief of parents after the loss of a child is well recognized. However, the
      concept of grief in children after the loss of a sibling or a parent has been
      accepted only recently. This paper describes the development and implementation
      of a bereavement program for staff and families in a children's hospital. The
      program is unique in that support is provided to both staff and families. Data
      gathering, goals of the program, the phases of implementation, and the specific
      components of support for each group are described. Initial efforts in evaluating
      the program and implications for the future are discussed.

PMID- 8133438
TI  - Self-efficacy, coping, and well-being among nursing students sexually abused in
      childhood.
AB  - Preparing nursing students to work with sexually abused children has received
      little attention by pediatric nurse educators. These students often are
      themselves survivors of such abuse. The population of undergraduate nursing
      students attending a major university was invited to participate in a mailed
      survey to test hypotheses concerning differences in self-efficacy, coping, and
      well-being between subjects who were sexually abused in childhood and those who
      were not. A total of 87 students (79 women and 8 men) responded by returning the
      completed survey. Forty-seven percent of the women (n = 37) and 38% of the men (n
      = 3) in the sample reported having had one or more unwanted sexual experiences in
      childhood. Significant correlations were found between self-efficacy and
      confrontive coping (r = .58), emotive coping (r = .49), and palliative coping (r
      = -.46); between well-being and emotive coping (r = -.24); and between well-being
      and palliative coping (r = -.25). One-way analysis of variance (ANOVA) techniques
      were used to analyze differences in self-efficacy, coping (confrontive, emotive,
      and palliative), and well-being between the two groups (abused = 40 and not
      abused = 47). A significant difference in emotive coping was found. These
      findings suggest that nurse educators and administrators need to be sensitive to
      pediatric nurses' childhood sexual experiences. Such nurses must be knowledgeable
      and emotionally equipped to support the child and family through the process of
      recovery. It is important for them to be aware of how their own coping strategies
      and well-being affect the care they provide vulnerable children.

PMID- 8133439
TI  - Coordinating a research program with a cadre of students.

PMID- 8133440
TI  - American children and immunizations: Part II, Program initiatives.

PMID- 8133441
TI  - The use of EMLA cream to reduce and/or eliminate procedural pain in children.

PMID- 8133442
TI  - The educator's role in facilitating change.

PMID- 8133443
TI  - Helping the parents of the dying child: an Israeli experience.
AB  - This small sample study attempted to define the problems families faced when
      their child was dying. The longitudinal approached allowed us to identify
      patterns of parental response and to identify patterns of nursing intervention
      that the parents found helpful. The results of the study have helped us teach
      other nurses how to more successfully work with these families.

PMID- 8133444
TI  - Functional comparison between HTLV-I envelopes originating from TSP/HAM or ATL
      cell lines.
AB  - The human T-cell leukemia type I (HTLV-I) virus is associated with two different
      diseases, adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I
      associated myelopathy (TSP/HAM). We have compared the viral envelopes originating
      from TSP/HAM and ATL patients, using the capacity of infected cells to form
      syncytia with receptor-expressing cells. We show that like the ATL cell lines,
      the TSP/HAM ones can form syncytia with a large panel of human target cells,
      including a variety of hematopoietic cell lines, as well as cell lines of
      neuroectodermal origin. None of the target cell lines tested was able to
      discriminate between TSP/HAM- and ATL-infected cell lines. When infected cells of
      TSP/HAM origin are cocultivated with cells of ATL origins, syncytia are never
      observed. This interference phenomenon suggests that the viruses expressed by the
      different cell lines utilize the same receptor.

PMID- 8133445
TI  - Comparison of anti-HIV-1 ADCC reactivities in infected humans and chimpanzees.
AB  - Despite its shortcomings as a disease model, the chimpanzee is still the most
      relevant animal model for human immunodeficiency virus type 1 (HIV-1) infection.
      Previous studies have revealed qualitative differences between human and
      chimpanzee anti-HIV-1 responses. In this study, the development of specific anti
      HIV-1 antibody-dependent cellular cytotoxic (ADCC) reactivities was evaluated in
      chronically infected chimpanzees and compared to the human response, because anti
      HIV-1 ADCC represents a major component of anti-envelope cytolytic response found
      in infected patients. Ten HIV-1-infected chimpanzees up to 5 years after the
      infection were investigated. Anti-HIV-1 ADCC-directing antibodies were detectable
      in only three of 10 infected chimpanzees, and in these animals, activity was
      apparent only several months after the HIV infection. In some of the infected
      animals, ADCC reactivity against infected cells preceded reactivity against gp120
      coated targets. When anti-gp120 ADCC-directing antibodies were apparent, they
      exhibited the same broad reactivity described in humans against different HIV
      isolates. The pattern of ADCC reactivities in infected chimpanzees is completely
      different from the well-characterized anti-gp120 cytotoxic reactivities present
      in HIV-1-infected patients. It is a relatively rare and late-occurring event that
      may have an important bearing on the lack of virus-induced pathogenesis in the
      chimpanzee model.

PMID- 8133446
TI  - Zidovudine therapy and health resource utilization in AIDS.
AB  - We wished to determine whether antiretroviral therapy with zidovudine first
      received when a person is diagnosed with AIDS was associated with diminished or
      increased direct health resource utilization. As a measure of health resource
      utilization, we examined all Medicaid-administered health care charges to adult
      Maryland residents diagnosed with AIDS from 1987 to 1989 who were part of the
      Human Immunodeficiency Virus Information System. We specifically compared those
      persons who first received zidovudine therapy either prior to or within 60 days
      of diagnosis of AIDS (n = 101) with those who never received zidovudine therapy
      (n = 279). Median survival time after diagnosis of AIDS in those who received
      zidovudine was 605 days and in those who did not receive zidovudine 235 days.
      After diagnosis of AIDS, median per-person lifetime direct health care charges to
      Medicaid were $66,200 in those who received zidovudine and $31,300 in those who
      did not receive zidovudine. The median incremental charge per year of life gained
      in zidovudine users was $34,600 compared with nonusers. Adjusting by proportional
      hazards regression for age, gender, race/ethnicity, HIV transmission risk group,
      AIDS-defining diagnosis, and length of follow-up, lifetime Medicaid charges were
      higher in zidovudine receivers. Compared with patients who did not receive
      zidovudine, patients who first received zidovudine at the time AIDS was diagnosed
      incurred higher cumulative lifetime charges, associated principally with longer
      survival time. The rate of resource utilization was not decreased by zidovudine
      use.

PMID- 8133447
TI  - Detection of rectal antibodies to HIV-1 by a sensitive chemiluminescent western
      blot immunodetection method.
AB  - Western blot with a time-dependent enhanced chemiluminescence immunodetection
      method (ECL-WB) was shown to be 100-fold more sensitive than standard commercial
      colorimetric Western blots (WB) for detecting serum IgG to human immunodeficiency
      virus type 1 (HIV-1). ECL-WB was then used to test rectal secretions from 15 HIV
      1 infected subjects (HIV+) and 7 uninfected subjects (HIV-) to document local
      IgG, IgA, and secretory component-associated immunoglobulin (SC-Ig) to HIV-1
      proteins. Fourteen of 15 HIV+ subjects had rectal IgA to at least 1 HIV-1
      protein, most often to gp41 (80%) or p24 (60%) and 14 (93%) had IgG to gp160,
      gp120, or gp41. Of seven HIV- subjects, none had detectable bands to HIV-1
      proteins. SC-Ig to HIV-1 proteins was detected in all five rectal samples tested.
      However, the antibody profiles differed from those of rectal IgA, suggesting more
      than one source of rectal IgA to HIV. ECL-WB requires individual optimization and
      interpretation for each specimen as well as expensive reagents and is, therefore,
      not currently applicable to screening assays. However, the method offers promise
      as a sensitive method to characterize low-level immune responses (IgG, IgA, and
      SC-Ig) to HIV-1 proteins at local sites such as rectal mucosae.

PMID- 8133448
TI  - Urban minority youth: alcohol and marijuana use and exposure to unprotected
      intercourse.
AB  - This article focuses on the use of alcohol and marijuana in the context of sexual
      relationships and the impact of these substances on the consistency of condom use
      by urban, minority youth. Regression models are presented to test for the effects
      of alcohol and marijuana use with sexual partners while controlling for the
      effects of respondents' sexual history. The results indicated that when alcohol
      or marijuana was used with a partner, the consistency of condom use decreased
      even when other variables related to sexual history were controlled for. Alcohol
      use had a greater negative effect on condom use for Hispanic men and marijuana
      for African-American women than it did for Hispanic women and African-American
      men. These findings argue for the need for targeted safer-sex intervention
      programs for urban, low-income, minority youth, and suggest that such programs
      may need to emphasize the increased risk of human immunodeficiency virus exposure
      that may result from substance use, casual sex, and sex with multiple partners.

PMID- 8133449
TI  - Population-based study of HIV-1 infection in 4,086 subjects in northwest
      Tanzania.
AB  - A population-based HIV-1 seroprevalence survey of 4,086 individuals, aged 15-49
      years, in the North Mara district of Tanzania from rural, periurban, and urban
      areas, including high-risk (prostitutes, and co-workers) individuals, was
      performed in 1989 and 1990. The overall seroprevalence was 7.3% (95% confidence
      interval, 6.5-8.1), with a gradient of seropositivity from high-risk 13.0% (9.1,
      16.8), urban 8.8% (7.6, 10.0), periurban 6.5% (4.7, 8.4), to rural 2.6% (1.6,
      3.7) subjects. Adjusted for population group, HIV-1 seroprevalence was
      significantly elevated for men over age 24 and for women 20-34 years old, while
      age-specific prevalence rates were similar for men and women in the rural area.
      Recent treponemal infection, measured by the rapid plasma reagin test, was not
      associated with HIV-1 seropositivity in men or women. These data suggest a
      growing HIV-1 epidemic paralleling rising rates in other rural areas of Africa
      distant from areas that have been previously recognized as having high
      prevalence.

PMID- 8133450
TI  - The relationship of 1988 state HIV testing policies to previous and planned
      voluntary use of HIV testing.
AB  - This study analyzed whether state HIV testing policies were related to
      individuals' previous and planned voluntary use of HIV testing. Testing plays an
      important role in the prevention and treatment of HIV infection, yet little is
      known about how policies are related to testing use. Most states mandate the
      conditions under which testing is performed, but states vary widely in their
      policies. This cross-sectional study analyzed individual-level data from the 1988
      AIDS Knowledge and Attitudes Survey, which was merged with state-level data on
      testing policies and incidence of AIDS cases. A multivariate regression model was
      used to assess the relationship of state policies to testing use, holding state
      AIDS incidence and individual characteristics (sociodemographics, AIDS knowledge,
      and risk status) constant. Individuals in states with policies protective of
      individual rights (i.e., early adoption of comprehensive antidiscrimination laws
      restricting screening by insurers and employers; provision of voluntary,
      anonymous testing) were significantly more likely to have been tested than
      individuals in comparison states (odds ratio = 1.5). Individual characteristics
      such as risk status, however, had the strongest relationships to testing use. No
      evidence was found that name-reporting requirements were related to previous or
      planned use of testing. Future research must address emerging testing issues such
      as policies covering the use of new testing technologies.

PMID- 8133451
TI  - T lymphocyte homeostasis after HIV seroconversion.

PMID- 8133452
TI  - Prophylactic zalcitabine and interferon-alpha for a large-bore needlestick
      exposure to human immunodeficiency virus.

PMID- 8133453
TI  - Reporting HIV infections.

PMID- 8133454
TI  - Low prevalence of human T-lymphotropic virus type I among patients with
      tuberculosis in Senegal.

PMID- 8133455
TI  - [Molecular genetics and biotechnology in medicinal plants: studies by transgenic
      plants].
AB  - The advances in molecular genetics and biotechnology in the field of medicinal
      plant research are discussed with focusing on the works using transgenic plants.
      Differentiated organ cultures and transgenic teratomas, incited by the infection
      with mutants of Agrobacterium Ti and Ri plasmids, were established in
      quinolizidine-alkaloid producing plants and Solanaceae plants. These cultured
      cells were used for the production and bioconversion of specific alkaloids
      produced in these plants. The methods of integration of foreign genes into
      medicinal plants were developed using an Ri binary vector. The mode of gene
      expression driven by TR1'-2' promoters was elucidated in transgenic medicinal
      plants, e.g., Nicotiana tabacum, Glycyrrhiza uralensis, Digitalis purpurea and
      Atropa belladonna. The genes for herbicide resistance, mammalian cytochrome P450
      and bacterial beta-hydroxydecanoylthioester dehydrase were transferred and
      expressed in plants either to confer herbicide-resistant trait or to change the
      pattern of metabolites. The cDNA clones encoding cysteine synthase responsible
      for sulfur assimilation and biosynthesis of non-protein amino acids were isolated
      and characterized from Spinacea oleracea and Citrullus vulgaris. The functional
      lysine residue was identified by site-directed mutagenesis experiments. An over
      expression system in Escherichia coli was constructed for the bacterial
      production of the plant specific non-protein amino acids. We made transgenic N.
      tabacum integrated with sense- and antisense-constructs of cysteine synthase cDNA
      driven by cauliflower mosaic virus 35S promoter for the purpose of genetic
      manipulation of biosynthetic flow of cysteine in plants. The future prospects of
      medicinal plant research are also discussed in the context of modern plant
      molecular biology.

PMID- 8133456
TI  - [Chemical and chemotaxonomical studies of ferns. LXXXV. Constituent variation of
      Microlepia marginata (2)].
AB  - A new chemotype of Microlepia marginata, P-type strain, was found in the Central
      districts of Japan. The two main constituents were characterized to be 2
      beta,15(R),16-trihydroxy-ent-pimar-7-en-3-one (fumotoshidin A) and 3 alpha-alpha
      L-arabinofuranosyloxy-15(R),16-dihydroxy-ent-pimar+ ++-7-ene (fumotoshidin
      arabinoside). The young fronds of this strain have reddish stripes, which is a
      common feature to Y-type strains also containing ent-pimarane-type glycosides.

PMID- 8133457
TI  - [Determination of synephrine in oriental pharmaceutical decoctions containing
      evodiae fructus by ion-pair high-performance liquid chromatography].
AB  - A simple and precise method was established for the determination of synephrine
      in oriental pharmaceutical decoctions containing Evodiae Fructus using high
      performance liquid chromatography with sodium dodecyl sulfate (SDS) as an ion
      pair reagent. Synephrine was eluted within 25 min without interference from co
      existing components using an ODS column and a mixture of water-acetonitrile-SDS
      phosphoric acid (70:30:0.5:0.1, v/v/w/v) as a mobile phase.

PMID- 8133458
TI  - [Phosphate ion-exchange with hydrotalcite-like compound in the presence of
      trypsin].
AB  - A Cl(-)-intercalated hydrotalcite-like compound (HTAL) is a promising material as
      a better phosphate adsorbent for further clinical use than the currently marketed
      aluminum hydroxide gels. In the preceding study, we found that Cl- ions in the
      interlayer of HTAL can be exchanged with phosphate ions equivalently. In the
      present study, we have investigated the adsorption of porcine pancreas trypsin on
      HTAL and the influence of trypsin adsorption on the phosphate/Cl- ion-exchange
      properties of HTAL. The isotherm for trypsin adsorption at 310K and pH 8.4 showed
      the curve of BDDT V type and gave an adsorption capacity of 88.6 mg/g for
      trypsin. The zeta-potential analysis of HTAL suggested that the trypsin
      adsorption on HTAL at pH 8.4 was restrained by the electrostatic repulsion
      between HTAL surface and trypsin with positive charge. XRD and nitrogen
      adsorption studies showed that trypsin was adsorbed on the external surface of
      HTAL by occupying the area (ca. 22 nm2) per trypsin molecule. The phosphate/Cl-
      ion-exchange reaction with HTAL was not affected by the presence of trypsin; the
      phosphate ion-exchange capacity reached 73.6 mg P/g from the solution containing
      3200 mg trypsin/dm3. On the other hand, the trypsin adsorption was significantly
      depressed by the loading of phosphate ions. The XRD analysis of the phosphate
      loaded HTAL revealed that the layered structure of hydrotalcite holds after the
      phosphate ion-exchange, but shows a slight increase of the interlayer distance
      from 0.3 nm to 0.5 nm by the intercalation of phosphate ions.

PMID- 8133459
TI  - [Spectrophotometric determination of uric acid in serum using a titanium (IV)
      porphyrin complex].
AB  - Aqueous solution of oxo[5,10,15,20-tetra(4-pyridyl)porphyrinato]titanium (IV)
      complex, a Ti-TPyP reagent, was found to be very useful for the
      spectrophotometric determination of hydrogen peroxide. The reagent (lambda max
      432 nm) reacts with hydrogen peroxide to form a monoperoxocomplex, resulting in a
      significant decrease of the absorbance at 432 nm. The decrease (delta A) in
      absorbance was proportional to the concentration of hydrogen peroxide. The Ti
      TPyP reagent was successfully applied to the assay of uric acid in the serum,
      using uricase to produce hydrogen peroxide through enzymatic oxidation. Using
      only 5 microliters serum, a linear relationship was obtained between delta A and
      uric acid concentration in the serum ranging from 5 x 10(-6) to 1 x 10(-3) M. The
      apparent molar delta A of uric acid was 2.2 x 10(5) M-1 cm-1. The relative
      standard deviation of repeated runs (n = 8) was 2.8% at 3.77 x 10(-4) M uric
      acid. The analytical recovery of uric acid (5 x 10(-4) M) added to the serum was
      96.8 to 105.0%. No pre-concentration and deproteinization were required to
      determine uric acid in the serum by the present method because of the high
      sensitivity and selectivity of the Ti-TPyP reagent for hydrogen peroxide.

PMID- 8133460
TI  - [Studies on zwitter-ionization of drugs. III. Synthesis and pharmacological
      activities of N-alkylcarboxylic acid derivatives of 1,2,3,4,10,14b
      Hexahydrodibenzo[c,f]-pyrazino[1,2-a]azepine and 2,3,4,9-tetrahydro-1H
      dibenzo[3,4: 6,7]cyclohepta[1,2-c]pyridine].
AB  - The N-alkylcarboxylic acids of 1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2
      alpha]az epi ne (6a) and 2,3,4,9-tetrahydro-1H-dibenzo[3,4: 6,7]cyclohepta[1,2-
      c]pyridine (6b) were synthesized and examined for pharmacological activities in
      vitro: an inhibitory effect on the monoamine [noradrenaline (NA) and 5
      hydroxytryptamine (5-HT)] uptake into the rat crude synaptosome, an inhibitory
      effect on the 5-HT- and NA-induced contraction in the isolated rabbit aorta and
      on the histamine- and acetylcholine-induced contraction in the isolated guinea
      pig ileum, and binding affinity for alpha 2-adrenoceptor and D2-receptor. The in
      vitro tests indicated that zwitter-ionization was capable of maintaining
      antihistaminic activity while greatly reducing other pharmacological activities
      such as effects on central nervous system. 3-[2,3,4,9-Tetrahydro-1H-dibenzo[3,4:
      6,7]cyclohepta[1,2- c]pyridin-2-yl]propionic acid (6b-2), selected as a candidate
      antiallergic agent having equally potent activities in rats and guinea-pigs,
      exhibited strong inhibitory effects on 48 h homologous passive cutaneous
      anaphylaxis (PCA) in rats (ED50 = 0.012 mg/kg, p.o.) and on histamine-induced
      bronchoconstriction in anesthetized guinea-pigs (ED50 = 0.0088 mg/kg, p.o.).

PMID- 8133461
TI  - Dermal and underlying tissue pharmacokinetics of salicylic acid after topical
      application.
AB  - The time course of salicylic acid at a dermal application site and in local
      underlying tissues below the site in rats was examined using a physiologically
      based pharmacokinetic model assuming first-order diffusional mass transfer
      between the dermis and underlying tissues. The concentrations of salicylic acid
      in tissues below the applied site were measured and compared with plasma
      concentrations and concentrations in similar tissues on the contralateral side.
      The direct penetration of salicylic acid was dominant only to a depth of 3-4 mm
      below the applied site for the first approximately 2 hr after application. The
      time course of salicylic acid in individual rats was modeled using known tissue
      blood flows and tissue-tissue clearances by (i) numerical integration and
      nonlinear regression of a series of differential equations representing events in
      individual tissues, and (ii) numerical integration and nonlinear regression of a
      single differential equation representation of the concentration-time course in
      an individual tissue with a polynomial representation of salicylate
      concentrations in other input tissues and an exponential representation of the
      input from the solution. Tissue-tissue clearances were deduced by both nonlinear
      regression and mass balance analysis (only for underlying dermis) using area
      under-the-curves from salicylic acid tissue penetration data in anesthetized
      rats. The relative importance of direct penetration and blood supply in
      determining the concentrations of salicylic acid in deeper tissues was assessed
      by simulations in which either no direct penetration occurred or there was zero
      input from blood. Simulations confirm that direct penetration is only evident in
      the superficial tissues for approximately 2 hr. An attempt was also made to
      examine the dermal pharmacokinetics of salicylic acid using statistical moments.

PMID- 8133462
TI  - Pharmacokinetic modeling of the sinusoidal efflux of anionic ligands from the
      isolated perfused rat liver: the influence of albumin.
AB  - This study contains a pharmacokinetic analysis on the efflux of organic anions
      from the liver into the bloodstream (sinusoidal efflux) with specific reference
      to the influence of albumin. The net sinusoidal efflux rate of
      dibromosulfophthalein (DBSP) from preloaded livers, being the resultant of
      sinusoidal efflux and reuptake of ligand by hepatocytes downstream the sinusoid,
      can be strongly increased by the presence of bovine serum albumin (BSA), a
      protein having multiple binding sites for DBSP. We previously attributed this
      effect to a reduction of reuptake through extracellular binding of the organic
      anion to the protein, rather than to an intrinsic stimulatory effect on the
      actual membrane transport process from the cells. In the present study we tested
      this hypothesis using a pharmacokinetic multicompartment liver model. This model
      resembles the parallel tube model in that the liver is described by several
      compartments placed in series instead of a single well-stirred compartment and it
      takes into account rates of dissociation and association in binding to proteins
      in the sinusoidal space. The model parameters were fitted from the sinusoidal
      efflux and biliary excretion data from efflux experiments measuring the
      stimulatory effect of various concentrations of BSA. Equilibrium binding of DBSP
      to albumin as well as the dissociation rate constant (koff) were determined in
      vitro with rapid filtration techniques. The experimental data could not be fitted
      satisfactorily when using the experimentally obtained values of the protein
      association and dissociation rate constants (kon and koff). However, they could
      be simulated accurately assuming 16 times higher values for the association and
      dissociation rate constant compared to those determined in vitro. Time constants
      of the perfusate flow, liver (re)uptake, and protein association and dissociation
      indicate that binding equilibrium does not exist within the sinusoids and that,
      in particular at low protein concentrations, the net sinusoidal efflux rate is
      association rate-limited: A large fraction of the ligand effluxed from the cell
      into the median is taken up by the hepatocyte before binding to the proteins
      occurs. Higher kon and koff values predicted by the model might indicate altered
      DBSP-albumin binding characteristics upon passage through the liver but
      alternatively can be explained by an intrinsic effect of albumin on the carrier
      mediated efflux process. Efflux experiments showed a marked stimulatory effect of
      the protein on sinusoidal efflux but only a moderate effect on biliary excretion,
      despite a strong decrease in liver content. These patterns indicate that
      sinusoidal efflux and biliary excretion occur from two different intracellular
      compartments that equilibrate slowly.

PMID- 8133463
TI  - Formed and preformed metabolite excretion clearances in liver, a metabolite
      formation organ: studies on enalapril and enalaprilat in the single-pass and
      recirculating perfused rat liver.
AB  - Single-pass and recirculating rat liver perfusion studies were conducted with
      [14C]enalapril and [3H]enalaprilat, a precursor-product pair, and the data were
      modeled according to a physiological model to compare the different biliary
      clearances for the solely formed metabolite, [14C]enalaprilat, with that of
      preformed [3H]enalaprilat. With single-pass perfusion, the apparent extraction
      ratio (or biliary clearance) of formed [14C]enalaprilat was 15-fold the
      extraction ratio of preformed [3H]enalaprilat, an observation attributed to the
      presence of a barrier for cellular entry of the metabolite. Upon recirculation of
      bolus doses of [14C]enalapril and [3H]enalaprilat, the biliary clearance,
      estimated conventionally as metabolite excretion rate/midtime metabolite
      concentration, for formed [14C]enalaprilat was again 10- to 15-fold higher than
      the biliary clearance for preformed [3H]enalaprilat, but this decayed with
      perfusion time and gradually approached values for preformed [3H]enalaprilat. The
      decreasing biliary clearance of formed enalaprilat with recirculation was
      explained by the dual contribution of the circulating and intrahepatic metabolite
      (formed from circulating drug) to excretion. Physiological modeling predicted (i)
      an influx barrier (from blood to cell) at the sinusoidal membrane as the rate
      limiting process in the overall removal of enalaprilat, (ii) a 15-fold greater
      extraction ratio or biliary clearance for formed [14C]enalaprilat over
      [3H]enalaprilat during single-pass perfusion, and (iii) the time-dependent and
      declining behaviour of the biliary clearance for formed [14C]enalaprilat during
      recirculation of the medium. In the absence of a direct knowledge of eliminating
      organs in vivo, this variable pattern for excretory clearance of the formed
      metabolite within the organ is indicative of a metabolite formation organ.

PMID- 8133464
TI  - Combined recirculation of the rat liver and kidney: studies with enalapril and
      enalaprilat.
AB  - Combined recirculation of the rat liver (L) and kidney (IPK) at 10 ml min-1 per
      organ (LK) was developed to examine the hepatorenal handling of the precursor
      metabolite pair: [14C]-enalapril and [3H]enalaprilat. Loading doses followed by
      constant infusion of [14C]enalapril and preformed [3H]enalaprilat to the
      reservoirs of the IPK or the LK preparation was used to achieve steady state
      conditions. In both organs, enalapril was mostly metabolized to its dicarboxylic
      acid metabolite, enalaprilat, which was excreted unchanged. At steady state, the
      fractional excretion for [14C]enalapril (FE = 0.45 to 0.48) and preformed
      [3H]enalaprilat (FE[pmi] = 1.1) were constant and similar for both the IPK and
      LK. The additivity of clearance was demonstrated in the LK preparation, namely,
      the total clearance of enalapril was the sum of its hepatic and renal clearances.
      However, the apparent fractional excretion for formed [14C]enalaprilat, FE(mi)
      and the apparent urinary clearance were time-dependent and higher than the
      corresponding values for preformed [3H]enalaprilat in both the IPK and LK. The
      FE(mi) and urinary clearance values further differed between the IPK and LK.
      Biliary clearance of formed vs. preformed enalaprilat displayed the same
      discrepant trends as observed for FE(mi) vs. FE(pmi) for the LK. These
      observations on the time-dependent and variable excretory clearance (urinary or
      biliary) of the formed metabolite vs. the constant, and much reduced, excretory
      clearance of the preformed metabolite are due to dual contributions to formed
      metabolite excretion: the nascently formed, intracellular metabolite which
      immediately underwent excretion and the formed metabolite which reentered the
      circulation, behaved as a preformed species. When data for the IPK and LK
      preparations were modeled with a physiological model with parameters previously
      reported for the L and IPK, all data, including metabolite excretory clearances,
      were well predicted. Model simulations revealed that the apparent FE(mi) differed
      between the LK and IPK preparations when the liver was present as an additional
      metabolite formation organ; the apparent excretory (urinary or biliary) clearance
      of the formed metabolite was further modulated by the volume of distribution of
      the metabolite, which altered levels of the formed, circulating metabolite.

PMID- 8133465
TI  - Comparison of four basic models of indirect pharmacodynamic responses.
AB  - Four basic models for characterizing indirect pharmacodynamic responses after
      drug administration have been developed and compared. The models are based on
      drug effects (inhibition or stimulation) on the factors controlling either the
      input or the dissipation of drug response. Pharmacokinetic parameters of
      methylprednisolone were used to generate plasma concentration and response-time
      profiles using computer simulations. It was found that the responses produced
      showed a slow onset and a slow return to baseline. The time of maximal response
      was dependent on the model and dose. In each case, hysteresis plots showed that
      drug concentrations preceded the response. When the responses were fitted with
      pharmacodynamic models based on distribution to a hypothetical effect
      compartment, the resulting parameters were dose-dependent and inferred biological
      implausibility. Indirect response models must be treated as distinct from
      conventional pharmacodynamic models which assume direct action of drugs. The
      assumptions, equations, and data patterns for the four basic indirect response
      models provide a starting point for evaluation of pharmacologic effects where the
      site of action precedes or follows the measured response variable.

PMID- 8133466
TI  - Accumulation profiles during quasi-uniform multiple dosing regimens.
AB  - An extension of the plasma area method of Chiou to the evaluation of accumulation
      profiles during quasi-uniform multiple dosing regimens (i.e., regimens with
      varying doses and/or dosing intervals within a certain time period which are
      repeated in the successive periods throughout the administration course) is
      presented. The derivations show, that the equations for the accumulation and
      steady state curves during quasi-uniform multiple dosing are similar or identical
      to these for the uniform multiple dosing case, if the constant time interval in
      the latter is replaced by the constant time period in the former. The equations
      derived can be used for rapid estimation of the time, required to reach a
      prespecified fraction of quasi steady state plasma level during quasi-uniform
      multiple dosing.

PMID- 8133467
TI  - Identifying oil-drop cataracts.

PMID- 8133468
TI  - Acute intraoperative suprachoroidal hemorrhage.

PMID- 8133469
TI  - Proliferation of cells on posterior surface of UBM2F/J lenses following YAG
      capsulotomy.

PMID- 8133470
TI  - Voltaren associated with medication keratitis.

PMID- 8133471
TI  - Mechanism for development of endophthalmitis.

PMID- 8133472
TI  - Lateral approach in superior cortex removal during small incision cataract
      surgery.

PMID- 8133473
TI  - Management of astigmatic keratotomy overcorrections by corneal sutures.
AB  - Astigmatic overcorrection is a significant possible complication of refractive
      surgical procedures such as radial keratotomy, astigmatic keratotomy, and
      combined radial and astigmatic keratotomy. We present the results of a study in
      which astigmatic overcorrection was reversed by suturing the astigmatic
      incisions. Videokeratoscopic studies of 15 patients showed that this technique
      induced a wide range of central corneal steepness, thus correcting variable
      amounts of astigmatic overcorrection. Mean preoperative uncorrected visual acuity
      was 20/100 while the mean postoperative uncorrected visual acuity was 20/40. One
      year after surgery, 13 patients had gained two or more Snellen lines of
      uncorrected vision; the remaining two had no improvement. Refraction was stable
      in all cases. No significant complications were observed at one year
      postoperatively. Corneal sutures may be used safely to manage overcorrections
      after astigmatic keratotomy or combined radial and astigmatic keratotomy with
      satisfactory results, even though the predictive value of the technique is
      limited.

PMID- 8133474
TI  - A new hydrogel intraocular lens design.
AB  - A new hydrogel intraocular lens was designed to improve fixation and support. The
      lens, IOGEL model 2000S, has a 6.00 mm optic that merges via a crescentic flange
      into a terminal loop for an overall diameter of 12.00 mm. The haptics are more
      flexible than existing loops and the design of the lens is based on a concept of
      minimum loop rigidity; that is, a haptic that is rigid enough to support the
      weight of a lens in aqueous within the capsular bag is considered adequate for
      modern cataract surgery. I evaluated the lens design's safety and efficacy.
      Excluding patients with pre-existing macular degeneration, the corrected acuity
      of all patients at last follow-up was 20/40 or better in 100%, 20/30 or better in
      95%, 20/25 to 20/20 or better in 85%, and 20/15 or better in 15%. The new haptic
      can accommodate compression of the capsular bag and allows early, reliable
      fixation. The centration of the lens was excellent early in the postoperative
      period and later after capsular fibrosis developed.

PMID- 8133475
TI  - Effect of pupil size and astigmatism on contrast acuity with monofocal and
      bifocal intraocular lenses.
AB  - We conducted a bicenter study to evaluate the effect of pupil size and corneal
      astigmatism on best corrected contrast acuity (BCCA) in patients with the True
      Vista bifocal intraocular lens (IOL) and compared the results with those in a
      matched group of monofocal patients. Best corrected contrast acuity was measured
      using the Regan Charts (96%, 50%, 25%, 11%) at four pupil sizes (2.0, 2.5, 3.5,
      6.0 mm) in three groups (Group 1: corneal astigmatism 0-0.50 D [n = 11]; Group 2:
      0.75-1.50 D [n = 11]; Group 3: 1.75-2.50 D [n = 4]). In monofocal eyes, BCCA
      between these astigmatic groups did not differ significantly at any contrast step
      or at any pupil size tested. However, BCCA decreased slightly with increasing
      pupil size in each group, and differences between 2.00 mm and 6.0 mm pupils were
      significant at each contrast level. In all bifocal groups, BCCA decreased
      significantly with increasing pupil size and also decreased with increasing
      corneal astigmatism; differences were significant at most pupil sizes and
      contrasts tested. In Group 1, BCCA was lower in eyes with bifocal IOLs than in
      eyes with monofocal IOLs at 25% and 11% contrast with a 2.5, 3.5, and 6.0 mm
      pupil; with a 2.0 mm pupil it did not differ significantly. In Groups 2 and 3,
      BCCA in eyes with bifocal IOLs was lower at all contrast steps and all pupil
      sizes tested. Our results indicate that corneal astigmatism in excess of 0.50 D
      reduces quality of vision in eyes with bifocal IOLs, while eyes with monofocal
      IOLs are not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133476
TI  - Antimicrobial efficacy and aqueous humor concentration of preoperative and
      postoperative topical trimethoprim/polymyxin B sulfate versus tobramycin.
AB  - We compared trimethoprim sulfate 0.1%/polymyxin B sulfate 10,000 units/mL with
      tobramycin 0.3% for preoperative sterilization of the ocular surface, aqueous
      humor concentration, and ocular safety and comfort in 99 patients who had
      cataract extraction and intraocular lens implantation. The organisms most
      frequently cultured from the conjunctiva at baseline were Staphylococcus
      epidermidis, Corynebacterium species, and Staphylococcus aureus, which were
      isolated from 66%, 15%, and 8% of the 95 specimens eligible for evaluation. All
      organisms identified in positive baseline conjunctival cultures except
      Staphylococcus epidermidis were completely eradicated in both groups on the day
      of surgery and five to seven days postoperatively. Staphylococcus epidermidis was
      eradicated on the day of surgery in 58% of patients in the trimethoprim/polymyxin
      group and in 68% in the tobramycin group. This organism was eradicated five to
      seven days postoperatively in 85% of patients in both groups. Mean aqueous humor
      concentration of trimethoprim sulfate at surgery was greater than the mean
      tobramycin concentration, but neither reached clinically significant inhibitory
      levels for most organisms. No significant differences were found in ocular safety
      and comfort.

PMID- 8133477
TI  - Long-term results using scleral-fixated posterior chamber intraocular lenses.
AB  - Transscleral ciliary sulcus fixation of a posterior chamber intraocular lens
      (IOL) is a technique for managing complicated cataract surgery, secondary IOL
      implantation, and IOL exchange. We performed a retrospective review of 32
      patients who had a minimum of six months and a mean of 13.3 months follow-up
      after transscleral ciliary sulcus fixation of a posterior chamber IOL. In 30
      patients, vision was maintained or improved following surgery. Complications were
      not uncommon; they were visually significant in three patients and necessitated a
      reoperation for late subluxation of the IOL in one other patient. Although the
      long-term visual results are encouraging, the postoperative complication rate of
      scleral-fixated posterior chamber IOLs is between that of posterior chamber IOLs
      inserted when the posterior capsule is intact and that of closed-loop anterior
      chamber IOLs.

PMID- 8133478
TI  - Astigmatic decay following small incision, self-sealing cataract surgery.
AB  - A series of 22 consecutive patients had phacoemulsification using a small (3.5 to
      4.0 mm), self-sealing incision. Preoperative keratometric analysis was performed
      using the EyeSys photokeratoscope. Results of this analysis were compared with
      keratometric data obtained at one week and at one month postoperatively. These
      comparisons were evaluated for surgery-induced cylinder and astigmatic decay at
      the 3, 5, and 7 mm corneal zones. At one week postoperatively, there was only
      mild against-the-rule change in cylinder at each corneal zone, and these changes
      showed minimal decay at the one month follow-up visit.

PMID- 8133479
TI  - Corneal endothelial cell loss after phacoemulsification using nuclear cracking
      procedures.
AB  - This study assessed corneal endothelial damage in endocapsular
      phacoemulsification surgery using a nuclear cracking procedure in which the
      nucleus was divided into four quadrants and emulsified. Forty-five eyes had
      phacoemulsification using this technique, and 33 eyes had phacoemulsification
      using undivided sculpting techniques (without cracking). We examined the extent
      of endothelial cell loss at one and three months after surgery using specular
      microscopy. We also measured ultrasound time, time spent for phacoemulsification,
      and infusion volume during surgery. Endothelial cell loss was significantly less
      in the nuclear cracking group than in the undivided sculpting group. Ultrasound
      time in surgery with cracking was significantly shorter than that in surgery
      without cracking. The time for the phacoemulsification maneuvers and the infusion
      volume were the same for both procedures. These findings indicate that the
      ultrasound time was shortened using the nuclear cracking technique and resulted
      in less corneal injury.

PMID- 8133480
TI  - Pathogenesis and management of the lens-iris diaphragm retropulsion syndrome
      during phacoemulsification.
AB  - After the ultrasonic tip is introduced into the highly myopic eye and inflow is
      activated, the anterior chamber deepens, the lens-iris diaphragm is displaced
      posteriorly, the iris becomes concave, and the pupil dilates from the weight of
      the water column above the eye. We define a known but undescribed syndrome--the
      lens-iris diaphragm retropulsion syndrome (LIDRS)--which is thought to be caused
      by abnormally loose zonules. The surgeon's reflexive action, lowering the
      infusion bottle height, reduces the weight of the water column but also reduces
      the infusion limit. We managed this situation with an inflow-splitting technique
      in which the infusion bottle height was lowered significantly and a Lewicky
      chamber maintainer connected to a second infusion bottle at the same height as
      the first bottle was introduced into the anterior chamber. Pressure monitoring
      that enabled simultaneous, synchronized recording of phacoemulsification and
      intraocular pressure fluctuations was used.

PMID- 8133481
TI  - Retrobulbar (intraconal) anesthesia with a curved needle: technique and results.
AB  - We report the results of two prospective studies of retrobulbar anesthesia using
      curved 25 mm and 28 mm needles. These studies were prompted by our experience
      with the 25 mm needle in more than 13,000 cases of intraconal anesthesia in which
      one case of postoperative ischemic neuropathy was the only complication. The
      technique involves the transcutaneous introduction of the curved needle at the
      middle of the lower lid, following a curved track close to the inferior orbital
      wall, around the globe, parallel to the plane of the medial orbital wall (i.e.,
      in a strictly sagittal plane lateral to the optical axis in primary gaze). No
      complications were noted in the prospective studies. Side effects were chemosis
      in 30% of cases, subconjunctival hemorrhage in 5%, and lid hemorrhage in 2%.
      Since these comparative studies, we have used the 28 mm needle without
      significant complications in more than 8,000 cases. This method of retrobulbar
      anesthesia is superior to peribulbar anesthesia, and because of its safety and
      reliability, is preferable.

PMID- 8133482
TI  - Single injection, low volume periocular anesthesia in 1,000 cases.
AB  - Periocular anesthesia is a proven alternative to retrobulbar anesthesia. A
      prospective evaluation of 1,000 cases was done to study the advantages of single
      point, low volume periocular anesthesia. This method is efficacious and has an
      excellent safety profile. The small needle length and the low volume of injected
      anesthetic enhance the safety. Supplemental anesthesia was needed in only 0.2% of
      cases. Chemosis was noted in 12.7%. In no case did surgery have to be postponed
      because of anesthesia-related complications. We believe this method is superior
      to other multipoint high volume methods of periocular anesthesia.

PMID- 8133483
TI  - Polishing methods for the lens capsule: histology and scanning electron
      microscopy.
AB  - Capsule opacification occurs when lens epithelial cells remains on the capsule
      after extracapsular cataract surgery. The cells divide and form fibers. The best
      way to prevent opacification is to remove all epithelial cells from the capsule.
      Our study compared the efficacy of different mechanical polishing methods in eyes
      in which cataracts were removed by endocapsular phacoemulsification through a
      miniature capsulorhexis. The capsular bag was polished using one of five
      techniques: metallic scrapers, silicone scrapers, Rentsch capsule curettes,
      irrigation/aspiration tip, or ultrasound irrigation/aspiration tip. Then a
      circular central portion of the anterior capsule was removed and processed for
      histology and scanning electron microscopy. A control group comprised unpolished
      central anterior capsules obtained by capsulorhexis before or after
      endophacoemulsification. The cleanest capsules were obtained by polishing with
      the ultrasound irrigation/aspiration tip.

PMID- 8133484
TI  - Age-related changes in the human lens: a comparison of Scheimpflug photography
      and lens density index.
AB  - Two quantitative techniques, Scheimpflug photography and the lens density index
      (LDI), were used to measure lens density in 52 patients. In the Scheimpflug
      technique, a digitized slitlamp camera provides peak and average nuclear density
      based on a densitometric analysis of the lens nucleus. The LDI is a
      psychophysical measurement of the difference between retinal scotopic thresholds
      for two wave-lengths of light. Both the Scheimpflug technique and LDI revealed an
      age-related increase in lens density. Peak and average nuclear density were
      highly correlated with the LDI.

PMID- 8133485
TI  - Integrated iseikonic equation for intraocular lens power calculations.
AB  - I present a simplified equation to calculate the iseikonic intraocular lens power
      and the resultant refractive error needed to achieve iseikonia with 5% tolerance
      limits. Iseikonic lens power calculations are indicated in the presence of a
      unilateral cataract and a phakic fellow eye. Iseikonia is often achieved by
      leaving the operated eye more myopic than the fellow eye. The induced myopia,
      with 5% tolerance limits, ranges from -0.75 +/- 2.75 diopters (D) for a posterior
      chamber lens to -2.40 +/- 2.75 D for an anterior chamber lens.

PMID- 8133486
TI  - Intraocular lens implantation in Terrien's marginal corneal degeneration.
AB  - A patient with Terrien's corneal marginal degeneration and a previous
      trabeculectomy had planned extracapsular cataract extraction with intraocular
      lens implantation. A corneal incision was made with a diamond blade on the
      degeneration furrow superiorly and was closed with a 10-0 nylon double-running
      suture with keratoscopic control.

PMID- 8133487
TI  - Uveoscleritis after excessive neodymium:YAG laser posterior capsulotomy.
AB  - A 66-year-old woman developed severe and recurrent scleritis and uveitis after
      neodymium:YAG capsulotomy performed 18 months after cataract extraction. Four
      cracks on the intraocular lens and plastic splinters in the vitreous indicated
      that excessive laser energy had been used. Inflammation was treated successfully
      only when a combination of dexamethasone acetate 0.1% drops (Maxidex), drops of
      diclofenac sodium 0.1% (Voltaren Ophtha), and systemic diclofenac sodium
      (Voltaren) was used. Inflammation might be explained by chronic irritation of the
      ciliary body by a displaced haptic or by an immune reaction triggered by damage
      to the ciliary body at the time of excessive posterior capsulotomy.

PMID- 8133488
TI  - Corneoscleral abscess resulting from a broken suture after cataract surgery.
AB  - An 82-year-old man had pain and decreased vision in his right eye 15 months after
      uncomplicated cataract surgery. Examination revealed a large corneoscleral
      abscess with a 2 mm x 1 mm area of fluorescein staining at the base of a broken
      protruding 10-0 nylon suture. Streptococcus pneumoniae was isolated from both the
      suture and base of the ulcer. Despite intensive topical, subconjunctival, and
      systemic antibiotics, a large corneal perforation developed, necessitating a 10
      mm tectonic penetrating keratoplasty. Long-term follow-up of patients after
      cataract surgery is important and should include an inspection of the limbal
      wound and removal of loose or broken exposed sutures. Suture-related
      complications will be eliminated if clinical studies prove the safety and
      efficacy of sutureless cataract surgery.

PMID- 8133489
TI  - Architectural design of a self-sealing corneal tunnel, single-hinge incision.
AB  - This report describes a corneal tunnel incision that is self-sealing and does not
      leak when pressure is applied to the posterior lip of the wound. The success of
      the incision is in the construction of a single hinge. Results in patients who
      had the procedure are discussed.

PMID- 8133490
TI  - Outside-in transscleral fixation for ciliary sulcus intraocular lens placement.
AB  - We describe a new technique of transscleral intraocular lens fixation in the
      absence of adequate posterior capsular support. This technique of suture
      placement within the ciliary sulcus employs routinely used instruments, requires
      minimum manipulation, and has good visual outcome and negligible complications.
      We performed five intraocular lens implantations using the technique with good
      visual outcomes in each. No significant intraoperative or postoperative
      complications were noted.

PMID- 8133491
TI  - Dexamethasone versus diclofenac sodium eyedrops to treat inflammation after
      cataract surgery.
AB  - We compared the postoperative anti-inflammatory effect of diclofenac sodium 0.1%
      and dexamethasone phosphate 0.1% in a prospective, randomized, double-masked
      pilot study. Anterior chamber inflammation was evaluated by measuring aqueous
      flare and cells with a laser flare-cell meter at one, three, 12, 30, and 60 days
      after cataract surgery. Flare values in the two groups did not significantly
      differ at any time, nor did aqueous cell counts at one, three, 12, and 60 days
      after surgery. At 30 days, however, cell count was significantly lower in the
      diclofenac group. Diclofenac sodium seems to be as potent as dexamethasone
      phosphate, as good as anti-inflammatory agent, and may replace corticosteroid
      therapy after cataract surgery.

PMID- 8133492
TI  - Using an anterior chamber maintainer to control intraocular pressure during
      phacoemulsification.
AB  - We describe a phacoemulsification technique that uses an anterior chamber
      maintainer (ACM) to control intraocular pressure. Continuous irrigation through
      the ACM maintains pressurized intraocular conditions throughout surgery and when
      the automated system is not activated. Intraocular pressure is stabilized at
      predetermined levels with minor fluctuations. Viscoelastics can be used in
      conjunction with the ACM.

PMID- 8133493
TI  - Prospective study of the Thornton irrigation/aspiration tip with small incision
      phacoemulsification.

PMID- 8133494
TI  - Consultation section. Posterior polar cataracts.

PMID- 8133495
TI  - A study of the Huntington's disease associated trinucleotide repeat in the
      Scottish population.
AB  - Accurate measurements of a specific CAG repeat sequence in the Huntington's
      disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish
      population showed a range from 35 to 62 repeats in affected subjects and eight to
      33 in normal subjects. A link between early onset of symptoms and very high
      repeat number was seen. For HD patients with the most common affected allele
      sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at
      onset of symptoms. There was variability in the transmitted repeat size for both
      sexes in the HD size range. We observed a significant increase of repeat size for
      paternal transmission of the disease and greater instability for paternally
      transmitted CAG repeats in the HD size range.

PMID- 8133496
TI  - Mutation size and age at onset in Huntington's disease.
AB  - The mutation responsible for Huntington's disease is a polymorphic (CAG)n repeat
      sequence which is expanded on affected chromosomes. The number of repeat units
      observed on 229 affected chromosomes varied from 27 to 102, while the control
      chromosomes showed a range of 7 to 34 repeats. There was a highly significant
      relationship between the size of the expanded region and age at onset, larger
      mutations being associated with earlier onset. This association was strongest in
      those with onset before 25 years of age but less clear cut with later onset, and
      is therefore unlikely to be useful for predicting age at onset in the context of
      presymptomatic testing.

PMID- 8133497
TI  - Identification of an expanded CAG repeat in the Huntington's disease gene (IT15)
      in a family reported to have benign hereditary chorea.
AB  - Benign hereditary chorea (BHC) is a rare autosomal dominant disorder
      characterised by the onset of non-progressive chorea in childhood and the absence
      of cognitive impairment. Using primers flanking the (CAG)n repeat in IT15,
      expansion of which is associated with HD, we have detected an abnormal PCR
      product in four affected members from one family where affected subjects were
      originally reported to have BHC. The expanded allele contains 38 repeats in the
      affected parent and this undergoes further enlargement to 39 and 45 repeats in
      the two affected offspring. We conclude that the diagnostic criteria for BHC
      should include a normal result from analysis for the (CAG)n expansion identified
      in HD.

PMID- 8133498
TI  - Huntington's disease in Grampian region: correlation of the CAG repeat number and
      the age of onset of the disease.
AB  - The identification of an unstable trinucleotide repeat as the mutation
      responsible for Huntington's disease (HD) has given the hope that additional
      information can be provided about age of onset and mode of action of the mutated
      gene. We present in this paper results of a clinical and molecular study of 82
      patients affected with HD from 46 pedigrees within the Grampian region, Scotland.
      Our results show a correlation between age of onset and size of the CAG
      expansion. This study has produced no overlap in mutation size between affected
      and unaffected alleles. The sex of the parent transmitting the mutated allele and
      the size of the normal allele have no significant effect on the clinical features
      of the disease. In the three juvenile cases the affected parent was the father
      but the number of cases is too small to produce statistical significance. An
      increase in the CAG repeat size is shown in the transmission of the gene in five
      cases, accompanied by an earlier age of onset in four; in three of these cases,
      the affected parent was the father. Eleven sib pairs were studied and there is a
      negative correlation between the difference in age at onset and the difference in
      repeat size. Thus there is some evidence of a relationship, but this is not
      statistically significant because of the small numbers involved. The presence of
      the same or different normal allele had no effect on age of onset in this small
      group. We suggest that additional factors, as yet unrecognised, influence the age
      of onset and clinical presentation of HD.

PMID- 8133499
TI  - Significant linkage disequilibrium between the Huntington's disease locus and
      markers at loci D4S10, D4S95, and D4S111 in Northern Ireland.
AB  - An analysis of the Northern Ireland Huntington's disease (HD) population of 75
      families showed significant linkage disequilibrium between the HD gene and DNA
      markers at D4S95, D4S10, and D4S111. As the linkage disequilibrium at loci D4S10
      and D4S111 is different from previous studies in the UK, but similar at locus
      D4S95, this suggests either that the HD mutation(s) in the Northern Ireland and
      British populations is not of common origin or that the haplotype of the common
      HD mutation has changed over time subsequent to divergence from a common origin.

PMID- 8133500
TI  - Presymptomatic testing for Huntington's disease: a world wide survey. The World
      Federation of Neurology Research Group on Huntington's Disease.
AB  - World wide data on presymptomatic testing for Huntington's disease using closely
      linked DNA markers show that 1479 persons at risk received completed test results
      up to the end of 1991. Testing has been carried out in 19 countries, with at
      least 88 centres involved, and numbers have levelled off after a peak in 1990.
      Only 5% of those at risk have been tested in six countries with the longest
      established programmes. Continued monitoring of international data will be of
      value in assessing the spread and impact of genetic testing, not only for
      Huntington's disease, but for other serious genetic disorders of later life.

PMID- 8133501
TI  - Attitudes of neurologists, psychiatrists, and psychotherapists towards predictive
      testing for Huntington's disease in Germany.
AB  - Predictive testing for Huntington's disease (HD) in Germany is performed by
      genetic counsellors, neurologists, psychiatrists, and psychotherapists. In order
      to evaluate the attitudes of neurologists, psychiatrists, and psychotherapists in
      Germany towards predictive testing for HD, a postal questionnaire was sent to
      this group. Two German Bundeslander were chosen, Baden Wurttemberg (BW) and
      Niedersachsen (NS). Of 469 persons interviewed the response rate was 32.6%. The
      questionnaire consisted of 17 items assessing sociodemographic data, acquaintance
      with HD patients, lay organisations, attitudes towards genetic counselling,
      presymptomatic and prenatal DNA testing, and reproduction of persons at risk for
      HD. More than 70% of the subjects were well informed about predictive DNA testing
      but knowledge about the details of the test procedure, especially the World
      Federation of Neurology (WFN) and International Huntington Association (IHA)1
      recommendations, was quite low (11.8%). Nevertheless, the majority would
      recommend predictive testing for HD although they anticipated problems for the
      probands. The majority of our respondents favoured psychological test and post
      test counselling for those tested. Concerning reproduction, most subjects
      favoured prenatal testing or that persons at risk should refrain from having
      children. We found that the opinions of practitioners and at risk persons
      differed with respect to the predictive DNA test and, particularly, to prenatal
      testing. Therefore the testing procedure could be improved if practitioners were
      better informed about the DNA test in general and about the attitudes and wishes
      of their patients.

PMID- 8133502
TI  - Ethical and social issues in presymptomatic testing for Huntington's disease: a
      European Community collaborative study. European Community Huntington's Disease
      Collaborative Study Group.
AB  - An analysis of social and ethical aspects of presymptomatic testing for
      Huntington's disease has been carried out, based on data on linked DNA markers,
      from four major testing centres in different European Community countries
      (Belgium, Italy, Netherlands, and United Kingdom). Information was available on
      603 applicants, with 213 final results given, of which 32% gave an increased
      risk. A series of specific issues and problems were documented systematically for
      all applicants, results being given on frequency of occurrence and illustrated by
      individual case histories. The principal issues could be grouped as problems of
      inappropriate referral, problems involving relatives, and problems relating to
      disclosure of results. At least one important problem was encountered in 46% of
      applicants, emphasising the importance of expert counselling, preparation, and
      support of applicants, and of close liaison between clinical, counselling, and
      laboratory staff. The extensive and detailed information available for
      Huntington's disease from this and other studies will be of considerable value in
      relation to genetic testing for other late onset genetic disorders and will be
      even more relevant to Huntington's disease now that specific mutation analysis is
      possible for this disorder.

PMID- 8133503
TI  - Predictive testing for Huntington's disease: after the gene. The United Kingdom
      Huntington's Disease Prediction Consortium.
AB  - The discovery of a mutation responsible for Huntington's disease (HD) offers the
      possibility of accurate predictive testing, as well as hope for treatment or
      prevention of this disease. We urge caution in the use of this new test as
      considerable ethical and counselling problems still exist, and new issues have
      arisen. The current guidelines for predictive testing should still apply, since
      it remains vital that subjects and their families have time to come to terms with
      the diagnosis of HD, and the implications of testing. Mutation analysis may allow
      the diagnosis of HD in isolated cases, or reverse a test result produced using
      linkage. Problems will arise as those at 25% risk may now receive a result
      despite the lack of support of their parent at 50% risk who may not wish to have
      their own status defined. In addition, couples who seek the exclusion test in
      pregnancy may find it difficult to investigate the pregnancy without producing
      information on themselves. Different centres should cooperate in maintaining the
      confidentiality of family members, ensuring that adequate counselling is given
      before results are produced which may affect the wider family.

PMID- 8133504
TI  - DNA storage and duplicate sampling: lessons learnt from testing for Huntington's
      disease.

PMID- 8133505
TI  - Prenatal diagnosis from maternal blood: simultaneous immunophenotyping and FISH
      of fetal nucleated erythrocytes isolated by negative magnetic cell sorting.
AB  - Fetal nucleated cells in the maternal circulation constitute a potential source
      of cells for the non-invasive prenatal diagnosis of fetal genetic abnormalities.
      We have investigated the use of the Magnetic Activated Cell Sorter (MACS) for
      enriching fetal nucleated erythrocytes. Mouse monoclonal antibodies specific for
      CD45 and CD32 were used to deplete leucocytes from maternal blood using MACS
      sorting, thus enriching for fetal nucleated erythrocytes which do not express
      either of these antigens. However, significant maternal contamination was present
      even after MACS enrichment preventing the accurate analysis of fetal cells by
      interphase fluorescence in situ hybridisation (FISH). To overcome this problem,
      we used simultaneous immunophenotyping of cells with the mouse antifetal
      haemoglobin antibody, UCH gamma, combined with FISH analysis using chromosome X
      and Y specific DNA probes. This approach enables selective FISH analysis of fetal
      cells within an excess of maternal cells. Furthermore, we have confirmed the
      potential of the method for clinical practice by a pilot prospective study of
      fetal sex in women referred for amniocentesis between 13 and 17 weeks of
      gestation.

PMID- 8133506
TI  - A specific mutation for Huntington's disease.

PMID- 8133507
TI  - Dynamic mutations on the move.

PMID- 8133508
TI  - Gametic but not somatic instability of CAG repeat length in Huntington's disease.
AB  - Instability of a CAG repeat in 4p16.3 has been found in Huntington's disease (HD)
      chromosomes. Unlike a similar repeat in the fragile X syndrome, the expanded HD
      repeat showed no evidence of somatic instability in a comparison of blood,
      lymphoblast, and brain DNA from the same persons. Four pairs of monozygotic HD
      twins displayed identical CAG repeat lengths suggesting that repeat size is
      determined in gametogenesis. In contrast with the fragile X syndrome and with HD
      somatic tissue, mosaicism was readily detected as a diffuse spread of repeat
      lengths in DNA from HD sperm samples. Typically, the modal repeat size was larger
      in the sperm DNA than in corresponding lymphoblast DNA, with the greatest degree
      of gametic mosaicism coinciding with the longest somatic CAG repeats. These data
      indicate that the developmental timing of repeat instability appears to differ
      between HD and fragile X syndrome, and that the fundamental mechanisms leading to
      repeat expansion may therefore be distinct.

PMID- 8133509
TI  - Familial predisposition to recurrent mutations causing Huntington's disease:
      genetic risk to sibs of sporadic cases.
AB  - Huntington's disease (HD) is associated with expansion of a CAG repeat in a new
      gene. We have recently defined a premutation in a paternal allele of 30 to 38 CAG
      repeats in the HD gene which is greater than that seen in the general population
      (< 30 repeats) but below the range seen in patients with HD (> 38). These
      intermediate alleles are unstable during transmission through the germline and in
      sporadic cases expand to the full mutation associated with the clinical phenotype
      of HD. Here we have analysed three new mutation families where, in each, the
      proband and at least one sib have CAG sizes in the HD range. In one of these
      families, two sibs with expanded CAG repeats are both clinically affected with
      HD, thus presenting a pseudorecessive pattern of inheritance. In all three
      families the parental intermediate allele has expanded in more than one
      offspring, thus showing a previously unrecognised risk of inheriting HD to sibs
      of sporadic cases of HD.

PMID- 8133510
TI  - Molecular analysis of late onset Huntington's disease.
AB  - Late onset Huntington's disease is characterised by onset of symptoms after the
      age of 50 and is usually associated with a milder course. We have analysed the
      CAG trinucleotide repeat within the HD gene in 133 late onset patients from 107
      extended families. The median upper allele size for the CAG repeat was 42 with a
      range of 38 to 48 repeats. A significant negative correlation (r = -0.29, p =
      0.001) was found between the length of repeat and age of onset for the total
      cohort. However, for persons with age of onset greater than 60, no significant
      correlation was found. In addition, no significant correlation was found between
      age of onset and size of the lower allele and the sex of the affected parent or
      grandparent. There was no preponderance of maternal descent for late onset cases
      in this series. This study shows that variation in repeat length only accounts
      for approximately 7% of the variation in age of onset for persons beyond the age
      of 50 and clearly shows how with increasing onset age the effect of the repeat
      length on this onset age seems to diminish.

PMID- 8133512
TI  - Structure characterization of membrane bound and surface adsorbed protein.
AB  - X-ray standing waves (XSW) have been used to study the topology of the protein
      cytochrome c, bound to a negatively charged model membrane and adsorbed at a
      metal surface. At the metal surface, cytochrome c forms an hexagonally close
      packed monolayer. A similar packing arrangement is observed at the surface of a
      self-assembled lipid film on silver. The data suggest that cytochrome c maintains
      its native globular structure upon surface binding and subsequent storage for an
      extended period. Further, the data are consistent with a protein docking
      mechanism wherein the heme plane is oriented perpendicular to and with its
      exposed edge facing the surface. This study demonstrates the utility of XSW as a
      new and powerful structural tool for investigating membrane- and surface-protein
      interactions.

PMID- 8133511
TI  - Dynamic mutation in Dutch Huntington's disease patients: increased paternal
      repeat instability extending to within the normal size range.
AB  - Analysis of the distribution of normal and expanded alleles of the polymorphic
      (CAG)n repeat in the IT15 gene in the Dutch population confirmed the presence of
      an expanded repeat on all Huntington's disease (HD) chromosomes. Our results show
      that the size distributions of normal and affected alleles overlap. Normal
      alleles range from 11 to 37 repeats and HD alleles contain 37 to 84 repeats. A
      clear correlation is found between age at onset and repeat length, but the spread
      of the age at onset in the major repeat range producing characteristic HD is too
      wide to be of diagnostic value. In the available parent-offspring pairs, maternal
      HD alleles show a moderate instability with a slight preponderance of size
      increase over size decrease. Paternal alleles have a bimodal distribution: the
      majority (69%) behave similarly to the maternal alleles, while the remainder
      (31%) show a dramatic expansion, the degree of which appears proportional to the
      initial size. This is shown in three out of four juvenile patients, who have
      repeats of 71, 74, and 84 copies, respectively, originating from expanded
      paternal HD alleles in the previous generation. Two sporadic cases are caused by
      expansion of 'large' normal paternal alleles of 32 and 34 repeats, respectively,
      to 46 copies. This not only confirms the diagnosis of HD in two de novo cases,
      but it also underlines the increased paternal instability. In addition paternal
      repeat instability was once detected within the normal range in two sibs who
      inherited 21 and 22 repeats, respectively, on the same paternal chromosome. In
      two Dutch HD families the segregation of the expanded (CAG)n repeat was found.
      Analysis of the (CAG)n repeat in our previously reported recombinants confirmed
      their disease status.

PMID- 8133513
TI  - Nucleic acid structure analysis. Mathematics for local Cartesian and helical
      structure parameters that are truly comparable between structures.
AB  - Analyzing nucleic acid structures in a comparable manner has become increasingly
      important as the number of solved structures has increased. This paper presents
      the concepts, mathematics, theorems, and proofs that form the basis of a new
      program to analyze three-dimensional DNA and RNA structures. The approach taken
      here provides numerical data in accordance with guidelines set at a 1988 EMBO
      workshop. Mathematical definitions are provided for all local structural
      parameters described in the guidelines. The definitions satisfy the guideline
      requirements while preserving the original physical intuition of the parameters.
      In particular, the rotational parameters are true rotations based on a simple
      physical model (net rotation at constant angular velocity), not Euler angles or
      angles between vectors and planes as is the case with other approaches. As a
      result, the mathematical definitions are symmetrical with the property that a 5
      degrees tilt is the same as a 5 degrees roll and a 5 degrees twist, except that
      the rotations take place about different axes. In other approaches, a 5 degrees
      tilt can mean a different amount of net rotation than a 5 degrees roll or a 5
      degrees twist. A second unique feature of the mathematics is that it explicitly
      incorporates the concept of a pivot point, which is the point about which a base
      in a base-pair rotates as it buckles, propeller twists, and opens. Pivot points
      enable one to model the physical motion of bases more accurately. As a result,
      they greatly reduce and/or eliminate the statistical correlations between
      rotational and translational parameters that arise as mathematically induced
      artifacts in other approaches. This paper, together with the statistical analysis
      in the companion paper for determining the locations of the pivot points,
      provides everything needed to understand the output of the program as it relates
      to individual structures.

PMID- 8133514
TI  - Crystallization and preliminary crystallographic analysis of two endo-beta-N
      acetylglucosaminidases, endo H and endo F1.
AB  - Endo H and F1 are endoglycosidases that cleave the oligosaccharide moiety of
      asparagine-linked glycoproteins by hydrolysis of the glycosidic bond in the N,N'
      diacetylchitobiose core. The two enzymes are specific for high-mannose
      oligosaccharides. Here, we report the crystallization and preliminary
      crystallographic analysis of Endo H and Endo F1. Crystals were grown by hanging
      drop vapor diffusion methods. Both proteins crystallize from crystallization
      buffers containing polyethyleneglycol 8000 and zinc acetate as precipitating
      agents in cacodylate buffer. The crystals of Endo H belong to the tetragonal
      space group P4(1)2(1)2 (or P4(3)2(1)2) with cell dimensions: a = 85.22 A, c =
      89.41 A. The crystals of Endo F1 belong to the hexagonal space group P6(1) (or
      P6(5)) with cell dimensions: a = 70.61 A, c = 100.32 A. Crystals of both proteins
      diffract to at least 1.8 A resolution.

PMID- 8133516
TI  - Crystallization and preliminary X-ray studies of cyclodextrin glucanotransferase
      from alkalophilic Bacillus sp. 1011.
AB  - Large crystals of cyclodextrin glucanotransferase (CGTase) from alkalophilic
      Bacillus sp. 1011, a typical alkalophilic enzyme, have been obtained at room
      temperature using polyethylene glycol 3000 and 2-propanol as precipitant. They
      belong to the triclinic space group P1 with the following unit cell constants: a
      = 64.93 A, b = 74.45 A, c = 79.12 A, alpha = 85.2 degrees, beta = 105.0 degrees
      and gamma = 101.0 degrees. The crystallographic asymmetric unit seems to contain
      two molecules of CGTase, with crystal volume per protein mass (Vm) of 2.41 A3/Da
      and solvent content of 49% by volume. The crystals diffract to at least 2.0 A
      resolution and they are suitable for X-ray analysis.

PMID- 8133515
TI  - Crystallization and preliminary X-ray analysis of PepC, a thiol aminopeptidase
      from Lactoccocus lactis homologous to bleomycin hydrolase.
AB  - Crystals of the recombinant thiol aminopeptidase PepC, from Lactoccocus lactis,
      have been obtained using the hanging-drop method of vapor diffusion from ammonium
      sulfate solutions. Crystals are rhombohedral, the space group is R32, a = 175.2
      A, c = 94.5 A (hexagonal setting). The asymmetric unit probably contains one
      monomer of a hexameric molecule-arrangement of 300 kDa which exhibits the
      crystallographic point group of symmetry 32. The crystals diffract to at least 3
      A resolution.

PMID- 8133517
TI  - Functional characterization of residues in the P-loop motif of the RecA protein
      ATP binding site.
AB  - We have introduced a large number of single amino acid substitutions at six
      positions that lie within the P-loop motif of the ATP binding site in the
      Escherichia coli RecA protein. The activity of each recA mutant was determined
      using genetic assays which assess the catalytic proficiency of the RecA protein
      for both homologous genetic recombination and recombinational repair of damaged
      DNA. The six residues displayed unique patterns of allowed versus non-allowed
      substitutions that define the functional and structural constraints at each
      position. Our results show that while the restricted mutability of Gly66 and
      Ser70 conform to expectations based on their positions in the RecA crystal
      structure, strict constraints are in effect at positions 68 and 69 that are not
      apparent in the RecA structure but would be compatible with the proximity of
      these side-chains to bound DNA. Thr74 shows a rather unexpected pattern of
      allowed substitutions that may reflect two distinct structural solutions to
      optimal stabilization of bound nucleotide. In addition, specific substitutions at
      Pro67 result in mutant RecA proteins that appear to discriminate between
      homologous genetic recombination and recombinational DNA repair.

PMID- 8133518
TI  - The parDE operon of the broad-host-range plasmid RK2 specifies growth inhibition
      associated with plasmid loss.
AB  - Recently, a 0.8 kb region of the broad-host-range plasmid RK2 has been shown to
      be sufficient to stabilize plasmids in a vector-independent, broad-host-range
      manner under some but not all growth conditions (Roberts, R. C. & Helinski, D. R.
      (1992). J. Bacteriol. 174, 8119-8132). This region encompasses the parDE operon,
      which encodes the small proteins ParD and ParE, both of which are required for
      the plasmid stabilization. This paper demonstrates that the 0.8 kb region encodes
      the capacity to inhibit cell growth of Escherichia coli, presumably of those
      bacteria that have lost plasmids carrying this stabilization region, and this
      inhibition appears to be associated with cell killing and bacterial cell
      filamentation. A good correlation was observed between the capacity of wild-type
      and mutated 0.8 kb regions to promote stable maintenance of a temperature
      sensitive RK2 replicon plasmid and to inhibit bacterial cell division under
      specified medium conditions. The properties of the wild-type and mutant 0.8 kb
      regions further indicate that the ParE protein is responsible for the growth
      inhibition and the ParD protein neutralizes the toxic activity of the ParE
      protein. This is consistent with the finding that the presence of the parD gene
      in trans destabilizes a temperature-sensitive RK2 replicon carrying a copy of the
      functional 0.8 kb region. This destabilization appears to be the result of ParD
      protein-mediated suppression of growth inhibition, thus allowing survival of
      cells that have lost the temperature-sensitive plasmid. These observations
      indicate that the 0.8 kb sequence of RK2 encodes a growth inhibition function
      that is likely to play a role in the plasmid stabilization.

PMID- 8133519
TI  - Bacteriophage T7 RNA polymerase and its active-site mutants. Kinetic,
      spectroscopic and calorimetric characterization.
AB  - It has been demonstrated that the amino acids Asp537, Asp812, Lys631, His811 and
      Tyr639 are involved in bacteriophage T7 RNA polymerase catalysis. In the present
      paper, we report kinetic, spectroscopic and calorimetric characterization of the
      wild-type and mutant T7 RNA polymerases generated at these five loci (D537N, E;
      K631M, R; Y639F, S, A, W; H811Q, A; D812N, E). The wild-type enzyme has a
      substantial amount of secondary structure as determined by CD analysis (alpha
      helix, 43%; beta-sheet, 14%; beta-turn, 25%; unordered, 18%). The CD spectra of
      12 mutants at five loci are very similar to that of the wild-type, except for the
      mutant Y639W. Within experimental error, the thermal transition temperatures
      measured by CD and DSC as well as the lambda max values of the fluorescence
      spectra were the same for the wild-type and all of the mutants. Therefore, the
      overall folding and stability of the mutant enzymes are very similar to those of
      the wild-type enzyme, although small local conformational changes cannot be
      excluded. For the synthesis of the pentamer pppGGACU, the mutants D537E and D812E
      showed an approximately two- to threefold decrease in (kcat)app and an
      approximately two- to threefold increase in (Km)app, relative to the wild-type,
      in contrast to the mutants D537N and D812N which exhibited no detectable
      activity. The mutant K631R showed a sevenfold reduction in (kcat)app and a two-
      to threefold increase in (Km)app, supporting our earlier observation with the
      mutant K631M that Lys631 may be involved in phosphodiester bond formation. The
      mutant Y639S can synthesize the trimer GGA with an approximately 50-fold decrease
      in (kcat)app and a tenfold increase in (Km)app, relative to the wild-type,
      underlining the importance of the phenyl ring of Tyr639. The mutant H811A, in
      which the side-chain at position 811 is incapable of forming a hydrogen bond, can
      synthesize the trimer GGA with an approximately tenfold decrease in (kcat)app and
      an approximately 35-fold increase in (Km)app. Thus, either the hydrogen-bonding
      capacity of this residue is non-essential or some other group can functionally
      substitute for the His811 side-chain. The wild-type enzyme showed significant
      effects of the base position in the sequence on the apparent binding constants
      for the NTPs. The kinetics of GpG-primed trimer, tetramer and pentamer synthesis
      on three 22 bp templates were investigated for the wild-type and mutant enzymes
      with measurable activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8133520
TI  - Host-inhibitory functions encoded by promiscuous plasmids. Transient arrest of
      Escherichia coli segregants that fail to inherit plasmid RK2.
AB  - An effective strategy for a plasmid to be maintained in a growing population of
      bacteria is to prevent the proliferation of newly formed daughter cells that lack
      the plasmid. In this study, we determined that the promiscuous, incompatibility
      group P plasmid RK2 encodes such a system. To induce large numbers of RK2-free
      segregants of an RK2-containing host, we designed a genetic system that made RK2
      replication temperature-sensitive. A double amber mutant of the trfA replication
      initiator gene was constructed to complement a trfA deletion mutant of an
      otherwise wild-type RK2 in an Escherichia coli supD(Ts) strain. At the permissive
      temperature (30 degrees C), RK2 was maintained stably in the strain. Shifting the
      cells to the non-permissive temperature (42 degrees C) resulted in the nearly
      synchronous appearance of cells lacking RK2. We found that the number of viable
      cells rose only slowly over a period of six hours, during which time the cells
      formed long filaments reaching 20 to 40 times the length of a normal E. coli
      cell. After six hours, the arrested cells regained the ability to divide and
      multiply exponentially, and the filaments were eventually reduced to normal-sized
      cells. Neither arrest nor filamentation required the host recA function.
      Inhibiting the replication of an RK2 mutant deleted for the par stability locus
      also induced the arrest of segregants lacking the plasmid, but the arrested cells
      were not filamented. Our results demonstrate that RK2 encodes at least two
      functions that are activated in a plasmidless segregant: (1) a filamentation
      inducing function specified by the par stability locus, and (2) a post
      segregational arrest function (psa) that inhibits the proliferation of
      plasmidless segregants independent of par. We discuss the possible roles of these
      functions in the stable maintenance of RK2.

PMID- 8133521
TI  - A cis-acting region required for the regulated expression of grg-1, a Neurospora
      glucose-repressible gene. Two regulatory sites (CRE and NRS) are required to
      repress grg-1 expression.
AB  - Grg-1 is a Neurospora gene which was identified as being a highly expressed
      glucose-repressible gene. A cis-acting regulatory region required for the
      regulated expression of grg-1 has been characterized. The regulatory region is
      found between 440 and 500 nucleotides upstream of the first major grg-1 start of
      transcription site and contains two distinct cis-acting regulatory elements. The
      upstream element consists of the sequence GTGACGTCAC, which is identical to the
      previously identified CRE (Cyclic AMP-Responsive Element). The second element is
      a newly defined cis-acting regulatory site. The element has the sequence
      TTGCTAGCAA and has been named NRS (Neurospora Repressor Site). DNA binding
      proteins can be shown to bind to both of these cis-acting regulatory elements.
      Experiments in which these sites were deleted demonstrate that both cis-acting
      regulatory elements are required to turn off the in vitro expression of the grg-1
      gene under conditions of glucose sufficiency.

PMID- 8133522
TI  - Complete sequence of the mitochondrial DNA of the chlorophyte alga Prototheca
      wickerhamii. Gene content and genome organization.
AB  - The complete nucleotide sequence of the circular mitochondrial (mt) DNA of the
      chlorophyte alga Prototheca wickerhamii has been determined (55,328 base-pairs,
      A+T content 74.2%). The genes identified encode three subunits of the cytochome
      oxidase, apocytochrome b, nine subunits of the NADH dehydrogenase complex (nad1
      to 7, nad4L and nad9), three ATPase subunits (atp6, atp9, atp1 (also referred to
      as atpA)), three ribosomal RNAs (5 S (rrn5), small subunit (srn) and large
      subunit (lrn) RNA), 26 tRNAs, and 13 ribosomal proteins. A total of five group I
      introns reside in lrn and cox1, two of which include intronic open reading frames
      (ORFs). Five free-standing ORFs longer than 60 codons are present. Three of these
      ORFs are counterparts to genes encoding proteins of unknown function in plant
      mitochondria (orf25 and orfB of angiosperms and orf244 of liverwort), whereas two
      of them are unique. Mitochondrial genes are encoded on both DNA strands in a way
      that suggests the existence of two transcription units, each including
      approximately one half of the mitochondrial genome. The two intergenic regions in
      which transcription is believed to initiate and terminate are about ten times
      longer than the other intergenic regions (1118 and 1993 nt versus 100 to 150 nt).
      A total of 29 recurring sequence motifs (30 to 200 nt long) have been found in
      intergenic regions. Nine different types of motifs are present, most of them
      arranged as tandem repeats. These motifs may be implicated in transcription, e.g.
      as signals for initiation, termination and/or processing. Phylogenetic analysis
      on the basis of the cox1 gene strongly suggested that P. wickerhamii and plant
      mitochondrial genomes are monophyletic. The finding of plant-specific
      mitochondrial genes such as orf25, orf244, orfB and rrn5 in P. wickerhamii
      mitochondria corroborates this idea.

PMID- 8133523
TI  - Structural analysis of Urechis caupo hemoglobin.
AB  - The structure of Urechis caupo hemoglobin in the cyanomet state has been refined
      to R = 0.148 at 2.5 A resolution. Although the tertiary structure is similar to
      that of other vertebrate and invertebrate hemoglobins the quaternary structures
      of this tetramer is unique as suggested by the earlier determination of the 5.0 A
      resolution structure. The G and H helices of the hemoglobin are on the outside of
      the tetramer facing the solvent in contrast to human hemoglobin where the G and H
      helices form inter-subunit contacts. A substantial number of tightly bound water
      molecules help mediate interactions between subunits. The unusual arrangement of
      subunits is consistent with the general lack of co-operativity of oxygen uptake
      for Urechis caupo hemoglobin.

PMID- 8133524
TI  - The effect of mathematics and coordinate system on comparability and
      "dependencies" of nucleic acid structure parameters.
AB  - This paper critically examines the methodologies used to analyze nucleic acid
      three-dimensional structure based on guidelines set at a 1988 EMBO workshop. The
      implications of these analyses cannot be fully understood without a thorough
      knowledge of how the numbers are calculated. This paper addresses one aspect of
      the calculations, namely the observed correlations between various parameters.
      These correlations are addressed in the mathematics by explicitly incorporating
      the concept of a pivot point, which is the point about which a base rotates as it
      buckles, propeller twists and opens. Pivot points enable one to model the
      physical motion of bases more accurately. As a result, they greatly reduce and/or
      eliminate the statistical correlations between rotational and translational
      parameters found in other approaches. The correlations that are reduced or
      eliminated are actually artifacts of the mathematics employed and do not reflect
      true structural properties of nucleic acids. The mathematics we have developed,
      including the mathematics of pivot points, are presented in the companion paper.
      Here, we explain how some of the observed correlations occur as a by-product of
      the method of calculation, while others are truly structural, and we show how
      optimum pivot points can be determined to minimize artifactual correlations. The
      observation that experimental bases often rotate about the long axis in a
      "propeller" motion as well as rotate about the Z-axis of each base, "opening"
      into the major groove, is evident in the location of the optimum region for the
      pivot point as determined in this study. We consider locating a pivot point as a
      calibration step to increase the agreement between physical intuition and the
      mathematics of our program.

PMID- 8133525
TI  - Papillomavirus capsids: a new approach to identify serological markers of HPV
      infection.

PMID- 8133526
TI  - Cervical dysplasia regression induced by all-trans-retinoic acid.

PMID- 8133527
TI  - Tamoxifen: trials, tribulations, and trade-offs.

PMID- 8133528
TI  - Breast cancer prognostic factors--the search goes on.

PMID- 8133529
TI  - AACR president assesses state of cancer research.

PMID- 8133530
TI  - Gene therapy for lung cancer still on hold.

PMID- 8133531
TI  - NCI issues information on falsified data in NSABP trials.

PMID- 8133532
TI  - A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies
      in a majority of women infected with human papillomavirus type 16.
AB  - BACKGROUND: Previous studies have demonstrated that genital infection with high
      risk types of human papillomavirus (HPV), most often HPV16, is the most
      significant risk factor for the development of cervical cancer. However,
      serologic assays that have been developed to identify high-risk HPV infection
      have either failed to associate serum reactivity with other indicators of HPV
      infection or have identified only a minority of HPV-infected individuals.
      PURPOSE: Our purpose was to determine whether a specifically developed enzyme
      linked immunosorbent assay (ELISA) could detect IgG anti-HPV16 virion antibodies
      in the sera of women who had tested positive for genital HPV16 infection by DNA
      based methods. METHODS: An ELISA was developed using newly developed HPV16 virus
      like particles as antigens to detect anti-HPV16 virion IgG antibodies. These
      particles are comprised of HPV16 structural proteins that are self-assembled in
      insect cells after expression by recombinant baculoviruses. The sera of 122
      women, whose HPV status had been previously evaluated by nucleic acid-based
      methods, were tested by this ELISA. RESULTS: The sera of 59% of women (32 of 54)
      positive for genital HPV16 DNA by polymerase chain reaction (PCR) were positive
      in the ELISA assay compared with sera from women who had tested negative for HPV
      DNA (P < .0005). In contrast, 6% of HPV DNA-negative women (two of 31) and 9% of
      women positive for low-risk HPV6/11 DNA (one of 11) were ELISA positive by this
      criterion. The sera of women who were DNA positive for two additional high-risk
      HPV types were evaluated; the sera of 31% of HPV18-positive (four of 13) and 38%
      of HPV31-positive women (five of 13) were positive in the HPV16 particle ELISA.
      The sera of 75% of HPV16 DNA-positive women with severe dysplasias (12 of 16)
      gave positive ELISA results. The sera of 67% of women (28 of 42) who tested
      positive for HPV16 DNA by both PCR and the less sensitive ViraType assay tested
      positive in the ELISA compared with 33% of women (four of 12) who were positive
      by PCR but negative by ViraType (P < .05). CONCLUSION: The majority of women with
      cervical HPV16 infection generate an IgG antibody response to conformationally
      dependent epitopes of HPV16 L1 that can be detected by ELISA. IMPLICATION: This
      particular ELISA, or a similar one incorporating virus-like particles of
      additional HPV types, may be useful in determining the natural history of high
      risk HPV infection and perhaps help to identify women at risk for developing
      cervical cancer.

PMID- 8133533
TI  - The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in
      lymph node-negative breast cancer patients.
AB  - BACKGROUND: The bcl-2 gene (also known as BCL2) encodes for a mitochondrial
      protein thought to prevent apoptosis of normal cells. The protein has been
      detected by immunohistochemical procedures in hormonally regulated epithelia.
      PURPOSE: We analyzed the predictive relevance of Bcl-2 expression on 6-year
      relapse-free and overall survival in lymph node-negative breast cancers in
      relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index,
      p53 protein expression, and estrogen receptor [ER] status) features. METHODS: The
      expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin
      embedded sections from 283 node-negative resectable breast cancers treated with
      local-regional therapy alone until relapse. The [3H]thymidine-labeling index was
      evaluated on histologic sections after incubation of fresh tumor tissue with
      [3H]thymidine, and ER content was determined by the dextran-coated charcoal
      absorption technique. RESULTS: A significantly higher fraction of Bcl-2-positive
      cells was observed in small, ER-positive, slowly proliferating, and p53-negative
      tumors than in large, ER-negative, rapidly proliferating, and p53-positive
      tumors. A stronger association was observed between Bcl-2 and p53 expression than
      between these variables and [3H]thymidine-labeling index. In univariate analysis,
      Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status
      were indicators for relapse-free and, with the exception of tumor size, overall
      survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to
      maintain its prognostic role for relapse-free and overall survival in the
      presence of p53 expression, whereas the [3H]thymidine-labeling index was still
      statistically significant as a predictor for both events. CONCLUSION: The
      predictive role of Bcl-2 expression on 6-year relapse-free and overall survival
      was mainly dependent on p53 expression.

PMID- 8133534
TI  - Breast cancer among young U.S. women in relation to oral contraceptive use.
AB  - BACKGROUND: While most studies have found no association between oral
      contraceptive use and breast cancer, several studies of younger women have
      reported an association with long-term oral contraceptive use. PURPOSE. We
      studied the relationship of patterns of oral contraceptive use to breast cancer
      risk among younger women. These women have had oral contraceptives available
      their entire reproductive lives and are now entering the breast cancer-prone
      years. METHODS: A population-based, case-control study of breast cancer was
      conducted in three counties in western Washington State among women born in 1945
      or later, ages 21-45. Case patients were 747 women with breast cancer diagnosed
      in 1983-1990 and identified through the Seattle-Puget Sound Surveillance,
      Epidemiology, and End Results cancer registry. Control subjects were 961 women
      identified by random-digit telephone dialing. Subjects were interviewed in
      person, using pictures of brands of oral contraceptives and calendars of life
      events as recall aids. RESULTS: There was no increased incidence of breast cancer
      associated with ever having used oral contraceptives. Because only 8% of this
      cohort had never used oral contraceptives, short-term users (< 1 year) were
      combined with never users as the reference group for further analyses. A small
      increased risk of breast cancer was associated with long duration of oral
      contraceptive use (odds ratio for > or = 10 years = 1.3; 95% confidence interval
      [CI] = 0.9-1.9; P for trend = .03), particularly among women aged 35 years or
      younger (odds ratio for > or = 10 years = 1.7; 95% CI = 0.9-3.1). Breast cancer
      was also modestly related to oral contraceptive use early in reproductive life
      (odds ratio for use within 5 years of menarche = 1.3; 95% CI = 1.0-1.8; P for
      trend = .04) and to use of high-progestin-potency oral contraceptives for at
      least 1 year (odds ratio = 1.5; 95% CI = 1.1-2.1). These associations were
      adjusted for age, age at menarche, term pregnancy, induced abortion, and family
      history of breast cancer. The associations were not further confounded by case
      control differences in education, religion, breast feeding of offspring, or
      infertility; in oral contraceptive contraindications, indications, or
      complications; or in measures of breast cancer detection such as mammography or
      breast biopsy. CONCLUSIONS: Long-term oral contraceptive use among young women or
      use beginning near menarche may be associated with a small excess breast cancer
      risk, possibly due to susceptibility to genetic damage in breast epithelial cells
      at ages of high breast cell proliferative activity. IMPLICATIONS: Future studies
      should investigate whether the patterns of risk we reported are present as this
      cohort ages.

PMID- 8133535
TI  - Identification of partial complementary DNA clones encoding a 59-kd protein with
      characteristics of a unique oncofetal antigen.
AB  - BACKGROUND: Oncofetal antigens (OFAs) are conserved tumor-associated autoantigens
      or transplantation antigens present on the surface of all major classes of rodent
      and human tumors and on midgestational fetal cells but not on normal neonatal or
      adult human and rodent tissues. A syngeneically derived monoclonal antibody, MAb
      115, recognizes murine OFAs of 44 and 200 kd in molecular mass. PURPOSE: Our goal
      was to clone and characterize the complementary DNAs (cDNAs) that encode these
      murine OFAs. METHODS: Rabbit antiserum raised against purified 44-kd OFA
      glycoprotein was used to screen a mouse embryo cDNA-lambda phage expression
      library. Recombinant phage clones positive for the expression of OFAs were
      detected by immunohistochemical staining, then isolated and plaque purified. The
      presence of an OFA-encoding sequence in the recombinant phage was confirmed by
      specific reaction of the expressed protein with MAb-115. Recombinant fusion
      protein was purified from the extracts of corresponding lysogens. Rabbit
      antiserum against purified recombinant fusion protein was raised, and the
      capacity of this antiserum to detect the expression of OFA on rodent tumor and
      fetal cells was determined by flow cytometry. In addition, immunoreactivity of
      tumor bearer and hyperimmune murine sera to bacterially expressed recombinant OFA
      protein was evaluated by enzyme-linked immunosorbent assay. The OFA-expressing
      insert DNA from plaque-purified lambda clones was subcloned into phagemid vectors
      for sequencing analysis. RESULTS: Antiserum derived against the isolated
      recombinant mouse embryo polypeptide mimicked MAb-115 in its specific binding to
      all OFA-positive rodent tumor and fetal cell lines tested and likewise did not
      show reactivity to normal adult tissues. This antiserum specifically recognized
      the native 44- and 200-kd OFAs in extracts of murine lymphocytic lymphoma.
      Furthermore, sera of tumor-bearing mice or mice immunized with purified OFA or
      intact, irradiated OFA-positive lymphocytic lymphoma cells also reacted with the
      recombinant fusion protein. The characterization of the isolated clone included
      nucleotide sequence information followed by analysis of the deduced primary
      structure of the protein. CONCLUSIONS: These data suggest that the isolated cDNA
      clones encode a distinct gene product which is widely expressed on the surface of
      tumor and fetal cells and represents the first characterized sequence of a true
      OFA. IMPLICATIONS: The availability of this cDNA, encoding a protein expressed
      only on tumor and fetal cells, provides a direct means to assess biological
      characteristics of malignant tissue which can be assayed by biochemical,
      histochemical, and molecular methods.

PMID- 8133536
TI  - Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the
      National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14.
AB  - BACKGROUND: Tamoxifen is advantageous in treating all stages of breast cancer.
      However, studies have suggested that incidence and severity of endometrial cancer
      increase in women treated with tamoxifen. PURPOSE: We compared rates of
      endometrial and other cancers in tamoxifen- and non-tamoxifen-treated patients
      and described the pathologic characteristics of the endometrial cancers. METHODS:
      Data were analyzed on 2843 patients with node-negative, estrogen receptor
      positive, invasive breast cancer randomly assigned to placebo or tamoxifen (20
      mg/d) and on 1220 tamoxifen-treated patients registered in NSABP B-14 subsequent
      to randomization. Average time on study is 8 years for randomly assigned patients
      and 5 years for registered patients. RESULTS: The incidence rates of liver,
      gastrointestinal, urinary tract, and nonuterine genital tumors were not increased
      by tamoxifen treatment. Twenty-five endometrial cancers were originally reported,
      one of which was reclassified after subsequent review. Two cases occurred in the
      placebo group in patients whose medical status subsequent to random assignment
      had required tamoxifen treatment. Twenty-three occurred in the tamoxifen groups.
      Twenty-one of the 24 originally reported endometrial cancers were FIGO stage 1;
      18 of 23 gradable cases were of good to moderate histologic grade. Four tamoxifen
      treated women died of uterine cancer. The average annual hazard rate of
      endometrial cancer as a first event within the first 5 years of follow-up in the
      randomized, tamoxifen-treated group was 1.2/1000 patient-years; the cumulative
      hazard rate was 6.3/1000. Findings for the registered, tamoxifen-treated group
      were similar. Including all originally reported endometrial cancers, the annual
      hazard rate through all follow-up was 0.2/1000 in the placebo group and 1.6/1000
      in the randomized, tamoxifen-treated group; the relative risk of endometrial
      cancer for the latter versus the former group was 7.5. Again for the latter
      group, using population-based rates of endometrial cancer from SEER data and
      information from another NSABP (B-06) trial, relative risks were 2.2 and 2.3,
      respectively. The 5-year cumulative hazard rate for disease-free survival in the
      randomized tamoxifen group was 38% less than that in the placebo group. Some data
      in this paper were provided by an investigator who submitted fraudulent data to
      the NSABP [see the "News" section]; therefore, the reader must read the entire
      text including Table 10 and the Editor's notes. In brief, data on 182 of the 2843
      randomly assigned patients and 37 of the 1220 registered patients were provided
      by the investigator in question. After review, 24 of the 182 records showed
      falsification, all involving characteristics of patients prior to random
      assignment. Of the 37 registered-patient records, 8 showed falsification.
      CONCLUSIONS: Risk of endometrial cancer increases following tamoxifen therapy for
      invasive breast cancer; however, net benefit greatly outweighs risk. Endometrial
      cancers occurring after tamoxifen therapy do not appear to be of a different type
      with a worse prognosis than are such tumors in non-tamoxifen-treated patients.
      IMPLICATIONS: Tamoxifen treatment for breast cancer should continue. In addition,
      the relative risk of endometrial cancer observed in B-14 tamoxifen-treated
      patients is consistent with the twofold relative risk used in the initial risk
      benefit computation for the NSABP breast cancer prevention trial.

PMID- 8133537
TI  - Enhancement of regression of cervical intraepithelial neoplasia II (moderate
      dysplasia) with topically applied all-trans-retinoic acid: a randomized trial.
AB  - BACKGROUND: Retinoids enhance differentiation of most epithelial tissues.
      Epidemiologic studies have shown an inverse relationship between dietary intake
      or serum levels of vitamin A and the development of cervical dysplasia and/or
      cervical cancer. Pilot and phase I investigations demonstrated the feasibility of
      the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen
      sponge insert and cervical cap. A phase II trial produced a clinical complete
      response rate of 50%. PURPOSE: This randomized phase III trial was designed to
      determine whether topically applied RA reversed moderate cervical intraepithelial
      neoplasia (CIN) II or severe CIN. METHODS: Analyses were based on 301 women with
      CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by
      serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with
      sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were
      inserted daily for 4 days when women entered the trial, and for 2 days at months
      3 and 6. Patients receiving treatment and those receiving placebo were similar
      with respect to age, ethnicity, birth-control methods, histologic features of the
      endocervical biopsy specimen and koilocytotic atypia, and percentage of
      involvement of the cervix at study. Treatment effects were compared using
      Fisher's exact test and logistic regression methods. Side effects were recorded,
      and differences were compared using Fisher's exact test. RESULTS: RA increased
      the complete histologic regression rate of CIN II from 27% in the placebo group
      to 43% in the retinoic acid treatment group (P = .041). No treatment difference
      between the two arms was evident in the severe dysplasia group. More vaginal and
      vulvar side effects were seen in the patients receiving RA, but these effects
      were mild and reversible. CONCLUSIONS: A short course of locally applied RA can
      reverse CIN II, but not more advanced dysplasia, with acceptable local side
      effects. IMPLICATIONS: A derivative of vitamin A can reverse or suppress an
      epithelial preneoplasia, lending further support to the notion that
      chemoprevention of human cancer is feasible.

PMID- 8133538
TI  - Phase I study of escalating targeted doses of carboplatin combined with
      ifosfamide and etoposide in treatment of newly diagnosed pediatric solid tumors.
AB  - BACKGROUND: The combination of carboplatin, ifosfamide, and etoposide has shown
      promising activity in a variety of relapsed childhood solid tumors but has not
      been studied in newly diagnosed patients. PURPOSE: The tolerance for and activity
      of escalating targeted doses of carboplatin combined with ifosfamide and
      etoposide (ICE) were assessed in children with advanced germ cell tumors or other
      rare solid tumors for which no standard therapy exists. METHODS: Fifteen children
      with newly diagnosed solid tumors received ICE chemotherapy. Individualized
      carboplatin doses were calculated to achieve a target area under the
      concentration x time curve (AUC) and adjusted for the glomerular filtration rate
      (estimated by 99mTc-labeled diethylene-triamine pentaacetic acid clearance).
      Cohorts of at least three patients received carboplatin at an initial target AUC
      of 6 mg.min/mL, with escalations of 2 mg.min/mL in subsequent cohorts.
      Carboplatin was given on day 1, followed by ifosfamide at 2 g/m2 per day and
      etoposide at 100 mg/m2 per day on days 2 through 4. All patients received at
      least two courses of therapy in the absence of progressive disease, and as many
      as eight courses could be given. RESULTS: The 15 patients received a total of 46
      assessable courses of ICE. Myelosuppression was the dominant toxicity; 30 courses
      (67%) resulted in hospitalization for febrile neutropenia. Neutropenia was dose
      limiting at the carboplatin target AUC of 12 mg.min/mL. One complete and eight
      partial responses were seen in the 14 assessable patients; two additional
      patients had at least partial responses documented at surgery or autopsy. Six
      patients are without evidence of disease at a median of 548 days after diagnosis.
      CONCLUSION: ICE chemotherapy, with the carboplatin dose based on a target AUC of
      10 mg.min/mL, is tolerable and has significant activity in a variety of rare
      malignancies, including extragonadal germ cell tumors. IMPLICATIONS: The
      combination of carboplatin, etoposide, and ifosfamide holds promise in the
      treatment of rare pediatric malignancies.

PMID- 8133539
TI  - Prognostic implications of p53 nuclear overexpression and high proliferation
      index of Ki-67 in adult soft-tissue sarcomas.
AB  - BACKGROUND: Morphologically similar soft-tissue sarcomas may behave in very
      different fashions, making it difficult to predict clinical outcomes and to
      properly design therapeutic interventions. In a preliminary study, we observed
      that TP53 mutations and nuclear overexpression of p53 protein were frequent
      events in soft-tissue sarcoma, and we noticed an association between p53-positive
      phenotype and poor clinical outcome. PURPOSE: We examined the potential clinical
      relevance of p53 overexpression in adults with soft-tissue sarcomas. We also
      studied the clinical implications of a high proliferation index. METHODS: A
      cohort of 174 adults with soft-tissue sarcomas were analyzed using anti-p53 and
      anti-Ki-67 antibodies and immunohistochemical assays on consecutive fresh frozen
      tissue samples. RESULTS: We observed a significant association between p53
      nuclear overexpression and tumor grade (P = .001) and tumor size (P = .01).
      Patients displaying a p53-positive phenotype had significantly reduced survival
      (P = .02). Similarly, a significant difference was observed between high
      proliferation index and tumor grade (P < .001) and reduced patient survival (P =
      .03). A high Ki-67 proliferation index was detected in association with p53
      nuclear overexpression. CONCLUSIONS: Overexpression of p53 protein and a high
      proliferation index strongly correlate with poor clinical outcome and reduced
      survival in patients having soft-tissue sarcomas.

PMID- 8133540
TI  - Testing tumor dormancy in breast cancer.

PMID- 8133541
TI  - Screening for breast cancer.

PMID- 8133542
TI  - Study on blackfoot disease: with special reference to evaluating its cutaneous
      microcirculatory status.
AB  - We evaluated the microcirculatory status of blackfoot disease by skin temperature
      measurement, laser Doppler flowmetry and capillary microscopy. The results of
      these assessments revealed a good correlation between the disease stage and the
      microcirculatory status. No effective therapy other than surgical amputation was
      recommended before. In this study, we treated this endemic disease with
      prostaglandin E1 (PGE1) infusion therapy. PGE1 was most effective in the
      erythematous stage and some minor ulcer with an improvement of microcirculatory
      status. However, PGE1 had no effect in severe ulcerative (ulcer > 0.5 cm) and
      gangrenous stages. These microcirculatory improvements foreshadowed the
      improvement of clinical manifestations. The microcirculatory status after PGE1
      treatment demonstrated the effectiveness of the therapy.

PMID- 8133543
TI  - Enteric parasites and antibodies to human immunodeficiency virus in homosexual
      men with diarrhea.
AB  - A total of 260 homosexual men with gastrointestinal illness, 77 of them with
      AIDS, were selected for a study of the prevalence of enteric parasites and its
      association with antibodies against human immuno-deficiency virus (HIV). HIV
      antibodies were demonstrated in the sera of all the AIDS patients and in 111
      (60.7%) of the non-AIDS patients. In the AIDS patients, 39 (50.6%) of them had
      enteric parasites and 33 had a single parasite recorded. By contrast, 49 (26.8%)
      of the non-AIDS patients had enteric protozoa detected and 25 of them had a
      single parasite. The protozoa most frequently recovered from the non-AIDS and the
      AIDS patients were Endolimax nana and Cryptosporidium, respectively. These
      findings indicate that immune dysfunction in AIDS patients can enhance the
      colonization of parasites and alter the spectrum of the intestinal flora.

PMID- 8133544
TI  - The role of ultrasound in scrotal trauma.
AB  - We reviewed the sonograms of 16 cases with scrotal trauma and documented the
      spectrum of abnormalities that may be present in sonography after a scrotal
      injury. The sonographic findings included scrotal hematoceles, post-traumatic
      epididymitis, epididymal hematoma, testicular hematoma and/or infarction,
      testicular rupture, testicular swelling and hyperemia. Ultrasound is able to
      distinguish intratesticular and extratesticular lesions. The integrity of the
      testis could be evaluated as well. It should be the imaging modality of choice
      for the evaluation of scrotal trauma.

PMID- 8133546
TI  - [A comparison of ankle fixation between two kinds of low-temperature plastic
      anterior ankle foot orthoses].
AB  - The low-temperature ankle foot orthosis (AFO) was designed in the anterior leaf
      type, called anterior AFO, to meet the need of indoor barefoot walking. It could
      be easily molded and remolded to fit the foot, as well as to adjust the position
      of the foot and ankle. Two kinds of low-temperature plastic anterior ankle foot
      orthoses, anterior encased and anterior direct molding ankle foot orthoses, were
      compared to analyze the effectiveness of ankle fixation in plantar flexion and
      inversion. Force was applied to each of the anterior AFOs at the anterior-middle
      and anterior-lateral sides to simulate the movement of ankle plantar flexion and
      inversion. At the same time, the deformation in plantar flexion and inversion of
      both anterior AFOs were recorded to analyze the relationship between force and
      the deformed angle. The results showed that plantar flexion deformed angles of
      the anterior direct molding AFO were 2.6 times more flexible than anterior
      encased AFO. The ankle inversion deformed angles of the anterior direct molding
      AFO were 3 times more flexible than the anterior encased AFO in inversion. These
      results support our belief that anterior encased AFO is more effective in
      controlling ankle plantar flexion and inversion than anterior direct molding AFO,
      especially for severe spastic hemiplegia in gait correction.

PMID- 8133545
TI  - The mucoceles or pyoceles of the paranasal sinuses.
AB  - Fifty-five mucopyoceles in 53 patients were diagnosed during the 10-year period
      from 1982 to 1992 in our department. These included 8 from the frontal sinus, 25
      from the maxillary sinus, 10 from the ethmoidal sinus, 1 from the maxillary and
      ethmoidal sinuses, 7 from the frontoethmoidal sinuses and 4 from the
      sphenoethmoidal sinuses. The patients ranged in age from 8 to 78 years (mean 47.1
      years). The ratio of males to females was 31 to 22. The rhinologic symptoms
      occurred most often in maxillary mucopyoceles and were rare in the other groups
      whereas ophthalmic symptoms were noticed in most of the cases. All of the cases
      received surgery and postoperatively most of the initial symptoms subsided except
      that two patients still had occasional diplopia and one did not recover at all
      from complete blindness. Two cases had a recurrence and one suffered from
      subarachnoid hemorrhage shortly after discharge. Surgery is the only treatment
      modality for mucopyoceles and the building of a new patent communication between
      the lesion and nasal cavity is important for the success of this surgery.

PMID- 8133547
TI  - Removal of renal cell carcinoma extending into the right atrium using
      cardiopulmonary bypass, profound hypothermia and circulatory arrest.
AB  - A 65-year-old man presented with renal cell carcinoma of the right kidney with a
      tumor thrombus extending up the vena cava to the right atrium. Cardiopulmonary
      bypass, profound hypothermia and total circulatory arrest were used to create a
      bloodless field for excision of the renal cell carcinoma and its tumor thrombus.
      Acute respiratory failure and deep jaundice developed after the operation and the
      patient was transferred to the intensive care unit for critical care. After
      respiratory therapy and nutritional support, the liver function was restored. The
      endotracheal tube was weaned one month later. The patient has had total
      resolution of all symptoms and there is no evidence of tumor recurrence of
      distant metastases after 6 months follow-up.

PMID- 8133548
TI  - Babinski-Nageotte syndrome: a case report.
AB  - A 68-year-old man developed a sudden onset of the left Wallenberg's syndrome with
      additional left hypoglossal nerve palsy and contralateral hemiparesis sparing the
      face. The clinical constellation, known as Babinski-Nageotte syndrome, is
      regarded as a combination of the medial and lateral medullary syndrome. Magnetic
      resonance imaging showed potential of in vivo confirmation of the underlying
      vascular insult, which clearly demonstrated an infarct area in the left half of
      the medulla oblongata.

PMID- 8133549
TI  - Two independent intracranial arteriovenous malformations: a case report.
AB  - Two independent intracranial arteriovenous malformations occurring to a single
      patient is rarely seen. A 23-year-old female suffered from a sudden onset
      weakness of the left side extremities and a generalized tonic-clonic seizure. A
      cranial CT revealed an intracranial hemorrhage in the right posterior temporal
      region and a highly enhanced mass in the left frontal lobe. On MR images,
      combination of subacute hematoma and serpentine vascular shadows in the right
      temporal area as well as clusters of vessels in the left frontal lobe were seen.
      Cerebral angiography confirmed one AVM in the right posterior temporal and the
      other the left frontal cortex.

PMID- 8133550
TI  - [Foreign body in the urinary bladder].
AB  - Foreign bodies in the urinary bladder are not uncommon, however, only a few cases
      have been reported in recent literature. This is not a fatal disease, however, it
      may lead to serious complications such as chronic cystitis, urolithiasis, or
      rectal abscess formation. These foreign bodies were inserted for autoerotic or
      unknown reasons by patients. In this paper we report 4 cases of foreign bodies in
      the urinary bladder. They include a cucumber, glass tube, chewing gum, and
      filliform catheter. We found that most of the foreign bodies in the urinary
      bladder can be removed endoscopically, but if the patients also had a lower
      urinary tract obstructive disease, removal necessitated surgical procedures. All
      of the four cases had no urological complications for at least one year after
      treatment.

PMID- 8133551
TI  - Helicobacter pylori infection.

PMID- 8133552
TI  - Growth of urban breastfed infants from low socio-economic group.
AB  - Breastfeeding has been considered the best mode of feeding the infant. In
      traditional countries like India, it has been the tradition among poor income
      groups of women and the universal adage breast feed as long as possible goes
      uncontested. However, the appropriate age at which supplementation should start
      is replete with controversy and varies between as early as 3-6 months. While the
      debate on when should supplementation be started continues, it is also important
      to know if the nutritional benefit is expressed in terms of growth of the infant,
      under the existing unhygienic conditions. This study was therefore undertaken.

PMID- 8133553
TI  - Persistent diarrhoea: management in algorithmic approach using a low-cost rice
      based diet in severely malnourished Bangladeshi children.
AB  - Easy and successful dietary management of persistent diarrhoea has been a long
      desired goal. Finding an efficient diet which is economically feasible, and easy
      to prepare in poor homes of developing countries, has not been easy. A dietary
      algorithm was followed to test the clinical efficacy of an inexpensive and easy
      to prepare diet made up with rice powder, egg white, glucose, and soya oil. We
      studied a cohort of 100 severely malnourished children aged between 3 and 36
      months with persistent diarrhoea in Dhaka Shisu (children's) Hospital,
      Bangladesh, during 1990. Initially on a milk-based diet, 26 children (26 per
      cent) improved while on a subsequent rice-based diet; 65 (88 per cent) of the
      remaining 74 children improved within a week, with a mean recovery period of 4
      days. Patients who did not improve with the rice-based diet were weaned earlier
      than those who improved. Nine patients failed to improve on the rice-based diet.
      They were given a soya formula, and only two improved. The remaining seven
      patients finally improved when a comminuted chicken diet was given. Eight
      patients died in the hospital with secondary infections of septicaemia and
      bronchopneumonia. This study offers a simple and effective algorithm on the
      management of persistent diarrhoea and also demonstrates the success of a rice
      based diet, showing promising and feasible means of management of persistent
      diarrhoea in patients with severe malnutrition.

PMID- 8133554
TI  - Acute diarrhoea and Campylobacter in Peruvian children: a clinical and
      epidemiologic approach.
AB  - A study performed on Peruvian children < 10 years of age and their controls
      showed that Campylobacter jejuni is a leading cause of diarrhoea. Infants 1 year
      old or younger were the most affected. The disease was usually moderately severe,
      although > 50 per cent of patients required i.v. fluid therapy. Campylobacter was
      also more frequent in malnourished patients, who come from socio-economically
      deprived groups, with overcrowding, poor sanitation, and frequent contact with
      domestic birds and animals. The seasonal behaviour suggests that diarrhoea caused
      by Campylobacter is endemic in this area.

PMID- 8133555
TI  - Routine high-dose vitamin A therapy for children hospitalized with measles.
AB  - Measles is without specific therapy and remains important globally as a cause of
      childhood death. In controlled studies, high-dose vitamin A therapy (Hi-VAT)-
      with 400,000 IU vitamin A--has been demonstrated to markedly reduce measles
      associated morbidity and mortality. We performed a retrospective study of the
      hospital records of 1720 children < 15 years of age who were hospitalized for
      measles, to determine the extent to which these findings, in research settings,
      are applicable to the case management of measles under conditions of routine
      hospital practice. The outcomes were studied of children hospitalized during two
      non-consecutive 2 year periods (1985-6 and 1989-90). A policy of Hi-VAT for all
      children hospitalized with measles was started during the intervening period. As
      compared with the group of children on standard therapy (n = 1061), children
      receiving Hi-VAT (n = 651) had a shorter hospital stay (mean 10 versus 13 days; P
      < 0.001), a lower requirement for intensive care (4.3 versus 10.5 per cent; P <
      0.001), and a lower death rate (1.6 versus 5 per cent; P < 0.001). No adverse
      effects of Hi-VAT therapy were observed. We conclude that a policy of high dose
      oral vitamin A (400,000 IU) supplementation in measles provides benefits which
      are equivalent to those previously observed only in controlled research trials,
      that it is highly cost effective, and that it should form part of the routine
      case management of all children hospitalized with measles.

PMID- 8133556
TI  - Respiratory syncytial virus infection in young children hospitalized with
      respiratory illness in Riyadh.
AB  - The occurrence of respiratory syncytial virus (RSV) infection among young
      children hospitalized with lower respiratory tract illness, at King Khalid
      University Hospital in Riyadh, was examined during the autumn-winter season
      between September 1991 and February 1992. Sixty-nine cases were diagnosed by
      immunofluorescent antibody staining of viral antigen in nasopharyngeal aspirates
      from 127 children, constituting 54 per cent of these patients. Virus culture was
      attempted only in a few cases, yielding two isolates. Most children were < 1 year
      of age (median 2 months). Bronchiolitis and bronchopneumonia were the major
      diagnoses on admission. Hospitalization was for an average of 5 days (range 1-36
      days). Treatment was supportive but most children received antibiotic therapy.
      There was no mortality. Few other bacterial or viral pathogens could be
      identified from RSV-positive or -negative patients. These results indicate that,
      during the season of infection, RSV may be the main pathogen of lower respiratory
      tract illness in hospitalized young children in this region.

PMID- 8133557
TI  - Convulsions with malaria: febrile or indicative of cerebral involvement?
AB  - Evaluation of 446 infants and young children (6 months to 5 years olds) with
      malaria parasitaemia showed a significant relationship (P < 0.05- < 0.001) (a)
      between coma and age, pattern of convulsions, haematocrit, and blood glucose, and
      (b) between the severity of parasitaemia and risk of convulsions, prevalence of
      hepatosplenomegaly, and severe anaemia. No significant relationship was observed
      between convulsions and temperature or haematocrit. Comatose children were older
      and had a higher prevalence of repeated convulsions, severe anaemia, and
      hypoglycaemia than non-comatose children. Convulsions, hepatosplenomegaly, and
      severe anaemia were more prevalent in children with moderate-severe parasitaemia.
      It is concluded that convulsions with malaria are more often a manifestation of
      cerebral dysfunction rather than being simply febrile in nature. All forms of
      cerebral dysfunction in malaria, including repeated convulsions, should be
      managed as being clinical manifestations of cerebral malaria.

PMID- 8133558
TI  - An assessment of the use of anthropometric measures for predicting low birth
      weight.
AB  - We report results of an evaluation of two anthropometric surrogates, viz chest
      circumference and mid-arm circumference, of birth weight. Optimal criteria for
      predicting birth weight below 2000 g and below 2500 g were provided by use of
      chest circumference alone. However, even the best criterion was not very
      sensitive indicating that use of anthropometric surrogates may have a limited
      practical value.

PMID- 8133559
TI  - Short course chemotherapy for tuberculosis in children.
AB  - In order to determine the efficacy of short course chemotherapy (SCC) for
      tuberculosis in children, 83 newly diagnosed cases in children < 12 years old
      were given SCC and were prospectively followed for 1-3 years. Seventy-one cases
      were treated for 6-9 months as they had mild to moderate involvement. Twelve
      cases were treated for 12 months as they had meningitis (7), disseminated
      tuberculosis (2), or miliary tuberculosis (3). The results showed that none of
      the children, at the end of follow up, showed evidence of active tuberculosis.
      All children tolerated the drugs well, with side effects noticed being mild,
      namely transient hepatitis (4), vomiting (1), and skin rash (1). It is suggested
      that SCC for 6-9 months using isoniazid (INH) and rifampicin along with other
      drugs when necessary is highly effective in most cases of tuberculosis in
      children and has several advantages over conventional chemotherapy of 18 months
      or longer duration.

PMID- 8133560
TI  - Aetiology of acute diarrhoea in hospitalized children in Rio de Janeiro City,
      Brazil.
AB  - Enteropathogens were investigated in 406 children aged 0-3 years with diarrhoea
      attending the Salles Neto Municipal Hospital. Enteric bacterial pathogens were
      isolated from 49 per cent of the children. Enterotoxigenic Escherichia coli
      (ETEC) (20.9 per cent), enteropathogenic E. coli (EPEC) (16.5 per cent),
      rotavirus (11.6 per cent), and Campylobacter (9.9 per cent) were the most common
      agents. Among clinical features, vomiting and fever were significantly associated
      with Rotavirus isolation (50.0 per cent), respiratory infection with Adenovirus
      (14.3 per cent), bloody diarrhoea with Campylobacter (12.5 per cent), and
      dehydration with EPEC (71.6 per cent).

PMID- 8133561
TI  - Rice-based oral rehydration solution: a controlled trial in Nepal.
AB  - The efficacy of rice-based (50 g/l) oral rehydration solution (ORS) was compared
      with standard glucose ORS in a randomized controlled trial in 148 children under
      5 years of age, suffering from acute watery diarrhoea leading to moderate and
      severe dehydration. The mean ORS intake in the two groups of children were 141.6
      and 205.2 ml/kg/24 hours, for rice ORS and glucose ORS, respectively (P < 0.001).
      The mean number of diarrhoeal stools in the first 24 hours in children of the
      rice ORS group was less when compared with the glucose ORS group (5.4 and 6.8/24
      hours, respectively; P < 0.001). This study suggests that rice ORS is a better
      alternative to standard glucose ORS in the management of diarrhoeal diseases in
      children.

PMID- 8133562
TI  - Understanding of growth monitoring charts by literate and illiterate mothers in
      northeast Brazil.

PMID- 8133564
TI  - Prediction of malnutrition by the ratio of the head circumference to the chest
      circumference.
AB  - This study was carried out in West Bengal, amongst 127 rural children aged 1-5
      years. It was found that the ratio of the head circumference to the chest
      circumference (H:C ratio) was valuable in predicting malnutrition. An increase in
      the ratio occurred 2-3 months before a drop in weight was noted; a decrease in
      the ratio was followed 2-3 months later by a gain in weight. Hence, it is felt
      that this method can be used in field work to forestall malnutrition.

PMID- 8133563
TI  - Cluster survey on neonatal tetanus mortality in Nigeria: observation on some
      clinical aspects.
AB  - A total of 2623 live births were recorded over a 12-month period during a cluster
      survey on neonatal tetanus (NNT) mortality in Kano Metropolis, Northern Nigeria.
      The survey involved a two-stage cluster sampling technique. Some aspects of the
      clinical features of NNT were evaluated. There were 79 neonatal deaths and 54 NNT
      deaths with NNT mortality rate of 20.6/1000 live births. The mean incubation
      period for NNT was 7.3 days, while the mean age at death was 12.7 days. The peak
      age at death was 8 days. Interval between mean age at onset and mean age at death
      was 5.4 days. Mean delay in presentation at health facilities for treatment was
      4.8 days. The possible significance of these features in prognosis is
      highlighted.

PMID- 8133565
TI  - Occult bacteraemia in a malarious area: presenting features and antimicrobial
      susceptibility.

PMID- 8133566
TI  - Brutality to twins in south-eastern Nigeria: the existing situation.

PMID- 8133567
TI  - White eyes and watery blood: a rapid appraisal procedure to find out about
      women's views of anaemia in Amukoko, Lagos State, Nigeria, as a basis for design
      of health promotion programmes.

PMID- 8133568
TI  - Clinico-bacteriological study of empyema thoracis in children.

PMID- 8133569
TI  - AIDS-related knowledge and attitude of high school students in Holon, Israel.
AB  - Four-hundred-and-eight high school students in the town of Holon, Israel,
      completed a questionnaire concerning their knowledge of HIV and AIDS, and their
      attitude towards the disease and the people affected by it. The highest scores
      for knowledge were amongst the 15-16 age group. Eighty-nine per cent of the
      students gave correct answers concerning the three major ways of HIV
      transmission: unprotected sex with HIV positive partner, sharing contaminated
      needles, and receiving contaminated blood transfusions. Students of the 14-16 age
      group expressed more tolerant attitude towards AIDS and HIV patients than the 16
      18 age group (P < 0.002). Nineteen per cent of the pupils are of the opinion that
      students diagnosed as HIV positive should not be allowed to continue their
      regular studies as they can endanger their fellow students. Twenty-eight per cent
      of the students declared that they would sever their relations with close friends
      diagnosed as HIV positive. Thirty-six per cent think it is not justified to
      compel medical staff to treat HIV positive patients. The attitude of the students
      towards an HIV positive 1-year-old adopted baby was divided as follows: 30 per
      cent think that the baby should be returned to the agency that handled the
      adoption, while 48 per cent think that the adopting parents should continue to
      care for him. The five principal sources of knowledge from which the students
      have learned about AIDS were: television (93 per cent); newspapers and
      periodicals (90 per cent); school education and biology classes (40 per cent);
      parents (39 per cent); and books (popular medical) (36 per cent).

PMID- 8133570
TI  - A piece of my mind. A difficult decision.

PMID- 8133571
TI  - Is reform coverage really universal?

PMID- 8133572
TI  - US Government inquiry bodies dismiss scientific misconduct charges against AIDS
      researchers.

PMID- 8133574
TI  - From the Assistant Secretary for Health, US Public Health Service.

PMID- 8133573
TI  - From the Food and Drug Administration.

PMID- 8133576
TI  - From the Centers for Disease Control and Prevention. Update: mortality
      attributable to HIV infection among persons aged 25-44 years--United States, 1991
      and 1992.

PMID- 8133575
TI  - From the Centers for Disease Control and Prevention. Distribution of STD clinic
      patients along a stages-of-behavioral-change continuum--selected sites, 1993.

PMID- 8133577
TI  - From the Centers for Disease Control and Prevention. Assessment of street
      outreach for HIV prevention--selected sites, 1991-1993.

PMID- 8133578
TI  - The overdiagnosis of Lyme disease.

PMID- 8133579
TI  - The overdiagnosis of Lyme disease.

PMID- 8133580
TI  - The overdiagnosis of Lyme disease.

PMID- 8133581
TI  - Conflict of interest policies: protecting readers or censoring authors?

PMID- 8133582
TI  - Sudden infant death syndrome: will establishing risk factors spuriously reduce
      incidence?

PMID- 8133583
TI  - Data audit for clinical trials.

PMID- 8133584
TI  - Estrogen therapy and the risk of breast cancer.

PMID- 8133585
TI  - Imaging for sinusitis.

PMID- 8133586
TI  - Predictors of laparoscopic complications after formal training in laparoscopic
      surgery.
AB  - OBJECTIVE: To evaluate the relationship between laparoscopic complication rates
      and surgeon-dependent variables following a laparoscopic training course. DESIGN:
      Participants were surveyed regarding their interval laparoscopic experience 3
      months and 12 months after the course. PARTICIPANTS: Course participants/survey
      respondents represented a cross section of urologic surgeons in the United
      States. A total of 181 individuals (61% of 297 participants) completed and
      returned the 3-month questionnaire. A total of 128 surgeons responded to the 12
      month questionnaire (78.5% of 163 participants). MAIN OUTCOME MEASURE: Logistic
      regression analysis tested the relationship between surgeons' complication rates
      and study variables. RESULTS: At 3 months, surgeons who performed clinical
      procedures without additional training were 3.39 times more likely to have at
      least one complication compared with surgeons who sought additional training (P =
      .03). At 12 months, surgeons who had attended the training course alone, were in
      solo practice, or performed laparoscopic surgery with a variable assistant were
      4.85, 7.74, and 4.80 times more likely, respectively, to have had a complication
      than their counterparts who attended the course with a partner, were in group
      practice, or operated with the same assistant (P = .004, P = .0008, and P =
      .0015, respectively). At both 3 and 12 months, laparoscopic complication rates of
      individual surgeons demonstrated a significant inverse correlation with the
      number of laparoscopic procedures performed. CONCLUSIONS: The rate of
      complications associated with the clinical learning curve can be decreased by
      additional education following an initial course in laparoscopy. An ongoing
      clinical association with surgeons performing similar procedures decreases long
      term complication rates.

PMID- 8133587
TI  - Vitamin status and intake as primary determinants of homocysteinemia in an
      elderly population.
AB  - OBJECTIVE: To describe the distribution of plasma homocysteine concentrations in
      an elderly population and to analyze the relationship between homocysteine level
      and intake of vitamins and serum levels of vitamins that serve as coenzymes in
      homocysteine metabolism. DESIGN: Cross-sectional analysis of homocysteine levels
      and vitamin blood levels and intake in elderly participants in the Framingham
      Study. SETTING: Population-based cohort in Framingham, Mass. PARTICIPANTS: A
      total of 1160 adult survivors, aged 67 to 96 years, from the original Framingham
      Heart Study cohort. MAIN OUTCOME MEASURES: Plasma homocysteine concentration
      correlated with plasma folate, vitamin B12, pyridoxal-5'-phosphate (PLP), and
      oral intakes of these vitamins, and the contribution of these vitamins to the
      prevalence of elevated homocysteine in the population. RESULTS: Homocysteine
      levels were positively correlated with age after controlling for vitamin
      concentrations. After controlling for age, sex, and levels of other vitamins,
      homocysteine exhibited a strong inverse association with plasma folate. When
      subjects were grouped by deciles of plasma folate, mean homocysteine was
      significantly higher in the lowest two folate deciles (15.6 and 13.7 mumol/L,
      respectively) than in the highest decile (11.0 mumol/L). Homocysteine
      demonstrated weaker, inverse associations with plasma vitamin B12 and PLP.
      Similar inverse associations were demonstrated between homocysteine and intakes
      of folate and vitamin B6, but not vitamin B12. Prevalence of high homocysteine (>
      14 mumol/L) was 29.3% in this cohort, and was greatest among subjects with low
      folate status. Inadequate plasma concentrations of one or more B vitamins appear
      to contribute to 67% of the cases of high homocysteine. CONCLUSIONS: These
      results indicate a strong association between homocysteine concentration and
      folate, vitamin B12, and vitamin B6 status, as well as age. It is possible that a
      substantial majority of the cases of high homocysteine in this older population
      can be attributed to vitamin status.

PMID- 8133589
TI  - Kallmann syndrome. From genetics to neurobiology.

PMID- 8133588
TI  - Randomized clinical trials in single patients during a 2-year period.
AB  - OBJECTIVE: To describe the feasibility of a single patient trial (SPT) service
      and study the influence of formal SPTs on therapeutic precision. DESIGN:
      Descriptive and evaluate study of SPTs. All planned trials were double-blind,
      randomized, multiple crossover trials. Other key features of individual trials
      were random assignment of order and assessment of predetermined explicit
      outcomes. Patients and physicians rated level of confidence in treatment before
      and after the SPT on visual analog scales. SETTING: Two-year experience
      (September 1988 to September 1990) of an SPT trial referral service available to
      physicians in an academic medical center. OUTCOME MEASURES: The number of planned
      and completed SPTs; proportion of completed trials yielding definitive answers;
      patient- and physician-rated levels of confidence in treatment pre- and post-SPT;
      time-motion studies to estimate resource consumption (costs) for selected SPTs.
      RESULTS: Of 34 completed trials, 17 were judged to give definitive results
      whereas 17 showed trends only. Results favored active treatment in 16 trials that
      led to treatment being continued (nine patients) or started (seven patients).
      Treatment was discontinued (seven patients) or not started (11 patients) based on
      18 trial results that demonstrated active treatment was ineffective (seven),
      harmful (two), or apparently equivalent (nine). Most patients (65%) reported no
      change in their already high level of confidence in therapy as a result of
      trials, whereas physicians' confidence levels in therapy either increased or
      decreased post-SPT depending on the direction of trial results. Patients
      consistently rated the SPT service as extremely useful. Time-motion estimates
      indicate that 16.75 staff hours were spent per trial leading to a direct cost
      estimate of approximately $450 to $500 per trial. CONCLUSION: We conclude that an
      SPT service is feasible, trial costs compare favorably with other conventional
      services, and clinicians appear to gain confidence and precision from SPTs. When
      patients or clinicians are uncertain about the value (including the possibility
      of side effects) of treatment for symptomatic chronic diseases, we believe an SPT
      can be offered to a patient and will likely yield results that will effect
      subsequent treatment.

PMID- 8133590
TI  - Diagnosis and treatment of seasonal affective disorder.

PMID- 8133591
TI  - Lessons from a clinic for the homeless. The Camillus Health Concern.
AB  - OBJECTIVE: To present the educational opportunities provided by a model clinic
      for homeless persons. DESIGN: Descriptive. PATIENTS OR OTHER PARTICIPANTS:
      Patients are those who are cared for at Camillus Health Concern clinic for the
      homeless in Miami, Fla. Other participants include students, residents, and
      faculty affiliated with the University of Miami (Fla) School of Medicine.
      INTERVENTION: Affiliation of the clinic with the medical school has shifted the
      clinic from a pure service model to an education and service model. MAIN OUTCOME
      MEASURES: Numbers of patients and encounters are presented, as well as student
      and resident rotations, numbers, and hours. RESULTS: Shifting to an education and
      service model has increased productivity of the clinic while providing a unique,
      multifaceted educational experience to students, residents, and faculty.
      CONCLUSIONS: Those factors that contribute to the success of this education and
      service model include the professional satisfaction that results from providing
      care to patients who previously have not had access to health care; a team
      approach that includes faculty, students, nurses, and social workers; an
      environment that fosters clinical judgment rather than expensive tests; and the
      opportunity to teach social responsibility in the process of providing health
      care. We encourage other schools to consider the development of clinics for the
      homeless as alternative ambulatory training sites.

PMID- 8133592
TI  - Credentialing in an era of change.

PMID- 8133593
TI  - Homocysteine and marginal vitamin deficiency. The importance of adequate vitamin
      intake.

PMID- 8133594
TI  - The dental AIDS cases--murder or an unsolvable mystery?

PMID- 8133595
TI  - Side effects of nicotine patches.

PMID- 8133596
TI  - Revaccination with pneumococcal and hepatitis B vaccines.

PMID- 8133597
TI  - Biofeedback for musculoskeletal pain.

PMID- 8133598
TI  - Flaws documented, reforms debated at congress on journal peer review.

PMID- 8133599
TI  - Cytology proficiency testing has stumped experts.

PMID- 8133600
TI  - NCI board votes to keep mammography guidelines.

PMID- 8133601
TI  - From the Assistant Secretary for Health, US Public Health Service.

PMID- 8133602
TI  - From the Centers for Disease Control and Prevention. Human rabies--New York,
      1993.

PMID- 8133603
TI  - From the Centers for Disease Control and Prevention. Tuberculosis--Western
      Europe, 1974-1991.

PMID- 8133604
TI  - From the Centers for Disease Control and Prevention. Comprehensive delivery of
      adult vaccination--Minnesota, 1986-1992.

PMID- 8133605
TI  - A piece of my mind. Frenzied calm.

PMID- 8133606
TI  - Mandatory national health service.

PMID- 8133607
TI  - Mandatory national health service.

PMID- 8133608
TI  - Mandatory national health service.

PMID- 8133609
TI  - Mandatory national health service.

PMID- 8133610
TI  - Mandatory national health service.

PMID- 8133611
TI  - Mandatory national health service.

PMID- 8133612
TI  - Mandatory national health service.

PMID- 8133613
TI  - Mandatory national health service.

PMID- 8133614
TI  - Mandatory national health service.

PMID- 8133615
TI  - Mandatory national health service.

PMID- 8133616
TI  - Solving the shortage of primary care physicians.

PMID- 8133617
TI  - Solving the shortage of primary care physicians.

PMID- 8133618
TI  - Solving the shortage of primary care physicians.

PMID- 8133619
TI  - Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study.
AB  - OBJECTIVE: To assess whether tubal ligation and hysterectomy affect subsequent
      risk of ovarian cancer. DESIGN: Prospective cohort study with 12 years of follow
      up. SETTING: United States, multistate. PARTICIPANTS: A total of 121,700 female
      registered nurses who were 30 to 55 years of age in 1976; the follow-up rate was
      90% as of 1988. MAIN OUTCOME MEASURE: Ovarian cancer of epithelial origin
      confirmed by medical record review. RESULTS: We observed a strong inverse
      association between tubal ligation and ovarian cancer, which persisted after
      adjustment for age, oral contraceptive use, parity, and other ovarian cancer risk
      factors (multivariate relative risk [RR], 0.33; 95% confidence interval [CI],
      0.16 to 0.64). The association was similar when we assessed tubal ligation status
      at the baseline questionnaire and excluded cases in the first 4 years to
      eliminate any possible short-term decrease in risk due to screening of the
      ovaries during ligation surgery. We noted a weaker inverse association between
      simple hysterectomy and ovarian cancer (RR, 0.67; 95% CI, 0.45 to 1.00). Neither
      vasectomy nor condom use by a partner was associated with risk of ovarian cancer.
      CONCLUSIONS: These data indicate that tubal ligation, and perhaps hysterectomy,
      may substantially reduce risk of epithelial ovarian cancer.

PMID- 8133620
TI  - Quantitative plasma D-dimer levels among patients undergoing pulmonary
      angiography for suspected pulmonary embolism.
AB  - OBJECTIVE: To test the hypothesis that a low D-dimer level has a high negative
      predictive value for acute pulmonary embolism (PE) among patients undergoing
      diagnostic pulmonary angiography. DESIGN: Blinded comparison of quantitative
      plasma D-dimer levels, measured using a monoclonal antibody assay, with pulmonary
      angiographic results from 173 patients with suspected acute PE. SETTING: Tertiary
      care setting at fur participating institutions. PATIENTS: Plasma samples were
      analyzed in 173 patients who underwent diagnostic pulmonary arteriography for
      suspected acute PE. MAIN OUTCOME MEASURES: Sensitivity, specificity, and
      predictive values of quantitative plasma D-dimer levels for the diagnosis of PE,
      using pulmonary angiographic data as the criterion standard test. RESULTS: Of 35
      patients with D-dimer values less than 500 ng/mL, only three had abnormal
      pulmonary angiograms. The negative predictive value of a plasma D-dimer level
      less than 500 ng/mL for acute PE was 91.4% (95% confidence interval [CI], 76.9%
      to 98.2%). D-dimer levels were greater than 500 ng/mL in 42 of 45 patients with
      PE and in 96 of 128 patients without PE (P = .016). Sensitivity, specificity, and
      positive predictive value of a plasma D-dimer level greater than 500 ng/mL for
      acute PE were 93.3% (95% CI, 81.7% to 98.6%), 25.0% (95% CI, 17.5% to 32.5%), and
      30.4% (95% CI, 22.8% to 38.1%), respectively. CONCLUSIONS: The results of our
      study indicate that quantitative plasma D-dimer levels can be useful in screening
      patients with suspected PE who require pulmonary angiography. Plasma D-dimer
      values less than 500 ng/mL may obviate the need for pulmonary angiography,
      particularly among medical patients for whom the clinical suspicion of PE is low.
      The plasma D-dimer value, assayed using a commercially available enzyme-linked
      immunosorbent assay kit, is a sensitive but nonspecific test for the presence of
      acute PE.

PMID- 8133621
TI  - Body weight and mortality. A 27-year follow-up of middle-aged men.
AB  - OBJECTIVE: To investigate the nature of the relation between body weight and all
      cause mortality. DESIGN: Prospective cohort study, following up men from 1962 or
      1966 (1962/1966) through 1988. SETTING/PARTICIPANTS: Harvard University alumni
      with a mean age of 46.6 years in 1962/1966 and without self-reported, physician
      diagnosed coronary heart disease, stroke, or cancer, who completed questionnaires
      on weight, height, cigarette smoking habit, and physical activity (n = 19,297).
      We calculated body mass index (weight in kilograms divided by the square of
      height in meters) using self-reported measures. MAIN OUTCOME MEASURE: All-cause
      mortality (4370 deaths). RESULTS: In multivariate analysis adjusting for age,
      cigarette smoking habit, and physical activity, we found a J-shaped relation
      between body mass index and mortality. Relative risks of dying for men with a
      body mass index of less than 22.5, 22.5 to less than 23.5, 23.5 to less than
      24.5, 24.5 to less than 26.0, and 26.0 or greater were 1.00 (referent), 0.99 (95%
      confidence interval, 0.89 to 1.20), 0.95 (0.87 to 1.05), 1.01 (0.91 to 1.10), and
      1.18 (1.08 to 1.28), respectively (P for linear trend = .0008). Among current
      smokers, the relation between body mass index and mortality was U-shaped, with
      lowest risk of death at a body mass index of 23.5 to less than 24.5. During early
      follow-up (1962/1966 through 1974), we also observed a U-shaped curve, this time
      with lowest mortality risk at a body mass index of 24.5 to less than 26.0. To
      minimize confounding by cigarette smoking and bias from antecedent disease and
      early mortality, we conducted analysis only among never smokers and omitted the
      first 5 years of follow-up (510 deaths). The corresponding relative risks from
      this analysis, adjusted for age and physical activity, were 1.00, 1.23 (95%
      confidence interval, 0.90 to 1.67), 1.06 (0.80 to 1.42), 1.27 (0.96 to 1.68), and
      1.67 (1.29 to 2.17), respectively (P for linear trend = .0001). CONCLUSIONS: In
      these prospective data, body weight and mortality were directly related. After
      accounting for confounding by cigarette smoking and bias resulting from illness
      related weight loss or inappropriate control for the biologic effects of obesity,
      we found no evidence of excess mortality among lean men. Indeed, lowest mortality
      was observed among men weighing, on average, 20% below the US average for men of
      comparable age and height.

PMID- 8133622
TI  - Risk of leukemia after treatment with pituitary growth hormone.
AB  - OBJECTIVE: To determine whether pituitary-derived human growth hormone treatment
      increases the subsequent risk of developing leukemia and lymphoma. DESIGN: Cohort
      study. SETTING: United States. PARTICIPANTS: A total of 6284 recipients of
      pituitary-derived human growth hormone distributed by the National Hormone and
      Pituitary Program between 1963 and 1985. MAIN OUTCOME MEASURES: Leukemia and
      lymphoma. RESULTS: Three cases of leukemia occurred in 59,736 patient-years of
      follow-up from the start of growth hormone therapy to case ascertainment at
      interview; this number was not significantly higher (P = .23) than the 1.66 cases
      expected in the US age-, race-, and gender-matched general population. Three
      additional cases, found in an extended follow-up that provided 83,917 person
      years of risk, yielded a minimum rate of leukemia that was significantly
      increased (six cases found, 2.26 expected; P = .028). The relative risk of
      leukemia in pituitary growth hormone recipients compared with the general
      population was 1.8 (90% confidence interval [CI], 0.82 to 7.5) for the defined
      follow-up and 2.6 (90% CI, 1.2 to 5.2) for the extended follow-up. Five of the
      six subjects who developed leukemia had antecedent cranial tumors (four
      craniopharyngioma, one astrocytoma) as the cause of growth hormone deficiency,
      and four had received radiotherapy. There was no increase in leukemia in patients
      with idiopathic growth hormone deficiency. The association of leukemia and
      craniopharyngioma was significant (P < .001). There was no excess of lymphoma in
      the cohort. CONCLUSIONS: This cohort of growth hormone recipients had a
      significantly increased rate of leukemia compared with the age-, race-, and
      gender-matched general population. However, the upper bound CI of the relative
      risk in our population (5.2) is well below the other estimates (7.6). Compared
      with the general population, our study population had more possible risk factors
      for leukemia (radiation, tumor) that may have contributed to the excess observed.
      The clustering of cases of leukemia in craniopharyngioma patients should be
      further evaluated.

PMID- 8133623
TI  - Urban violence in Los Angeles in the aftermath of the riots. A perspective from
      health care professionals, with implications for social reconstruction.
AB  - Beginning April 29, 1992, Los Angeles, Calif, was engulfed in a 3-day
      insurrection reflecting the residents' responses to a legal ruling. Unlike the
      media-painted picture, this article argues that the enormous outburst of violence
      and consequential property destruction was not the exclusive domain of the
      citizens of South-Central Los Angeles and that available data will not support
      the maintenance of the prevailing uneven distribution of civic and state
      resources in health care, educational programs, and economic opportunities. What
      it does support is the proposal for a more equitable allocation of resources
      among institutions, groups, and peoples, complemented by community empowerment, a
      more civic-oriented police operation, and a more rational approach to social
      reconstruction in which all elements of the society are full participants.
      Finally, the article suggests that augmentation of the present "law and order"
      approach and the paramilitary police already have proven economically
      ineffective. Given the dominant role of the medical profession in social and
      civic life, it is now appropriate for the medical profession to enter the debate
      on policies of health improvement, violence deterrence, and the general field of
      social reconstruction.

PMID- 8133624
TI  - The rational clinical examination. Does this patient have a clinically important
      carotid bruit?

PMID- 8133625
TI  - Routine iron supplementation during pregnancy. Policy statement. US Preventive
      Services Task Force.

PMID- 8133626
TI  - Routine iron supplementation during pregnancy. Review article. US Preventive
      Services Task Force.

PMID- 8133627
TI  - Primary prevention of ovarian cancer.

PMID- 8133628
TI  - More peering into editorial peer review.

PMID- 8133629
TI  - The impact of US health system reform on medical education. Call for papers.

PMID- 8133630
TI  - Flood, sweat, and tears--trying to build 'emotional levees'.

PMID- 8133632
TI  - Blood donation from patients with hemochromatosis.

PMID- 8133631
TI  - The public and the controversy over abortion.

PMID- 8133633
TI  - Diagnosis of giardiasis.

PMID- 8133634
TI  - Agrotherapy--new concept of rehabilitation for chronic schizophrenics in
      Pakistan.
AB  - The provision of comprehensive programme for mental health in the community
      setting has achieved an important place in the field of psychiatric
      rehabilitation. The concept of agrotherapy which is based on the philosophy of
      keeping patients occupied in a rural and agricultural setting with more
      structured activities has been found to be a promising innovation for the
      rehabilitation of chronic schizophrenics in this regard. This paper describes the
      results of a three years follow-up study conducted at Fountain House Farm,
      Farooqabad to evaluate the effectiveness of agrotherapy. The findings are
      discussed in terms of practical implications of this innovative approach in the
      rehabilitation of chronic schizophrenic patients.

PMID- 8133635
TI  - Intraoperative frozen section consultation: an analysis of accuracy in a teaching
      hospital.
AB  - This is a retrospective quality assurance study of all frozen sections done at
      The Aga Khan University Hospital during a six year period (1986 to 1991). There
      were 1,031 frozen sections out of a cumulative total of 42,985 surgical specimens
      (2.39%). Nine hundred and severity-six (94.66%) were concordant. In 92 (8.9%)
      fresh specimens were brought from other hospitals of Karachi, in 37 cases (3.58%)
      the diagnosis was deferred till the evaluation of permanent paraffin sections and
      18 (1.74%) were discordant with 7 (0.67%) false positive and 11 (1.06%) false
      negative. Among the discordant cases, 9 were attributed to misinterpretation, 7
      due to sampling errors and 2 due to technical reasons. Some of these errors might
      have been avoided, but appear to be an irreducible minimum.

PMID- 8133636
TI  - Endoscopic correction of vesicoureteric reflux in children.
AB  - Vesicoureteric reflux (VUR) is a common cause of recurrent urinary tract
      infections in children. Mild reflux (grade I-II) is usually managed
      conservatively with antibiotics but severe degree of reflux (grades III, IV, V)
      requires surgical intervention. We present our initial experience with endoscopic
      correction of vesicoureteric reflux by sub-ureteric teflon injection (STING) in
      ten patients. Results are available for 15 ureters with a success rate of 86.6%.
      There was no change in the grade of VUR in two ureters. There were no
      complications. Endoscopic correction of vesico-ureteric reflux by sub-ureteric
      teflon injection is effective and simple with no pain to the child. It averts the
      need for open operations.

PMID- 8133637
TI  - Colposcopy in the diagnosis of human papilloma virus infection, cervical
      intraepithelial neoplasia and invasive carcinoma.
AB  - Colposcopic diagnosis of 156 different lesions of the cervix was compared with
      histologic examination of the cervical punch biopsies. Colposcopy showed high
      degree of sensitivity and specificity (96% and 99.2%) in cases of carcinoma of
      the cervix. In cervical intraepithelial neoplasia (CIN) it showed a sensitivity
      of 82.8% and specificity of 49.6%, while in subclinical papilloma virus infection
      (SPI), it showed high degree of specificity (93.7%) but poor sensitivity (19.7%).

PMID- 8133638
TI  - Acute nonlymphoblastic leukaemia in adults.
AB  - Fifty-four cases of adult acute nonlymphoblastic leukaemia (ANLL) were studied.
      Their main symptoms were weakness and easy fatiguability (80%), fever (78%) and
      bleeding manifestation (48.38%). Our patients were younger (median age 34 years)
      and the disease was more advanced at the time of presentation than that seen in
      the West. FAB morphological classification of adult ANLL cases showed M2 (44.44%)
      the most predominant type followed by M4 (24%), M5 and M6 were less common
      (3.7%). Majority of ANLL cases (68.51%) occurred up to the age of 40 years. Our
      results are comparable to European and consistent with Pakistani and Libyan
      studies.

PMID- 8133639
TI  - Trichomonas tenax in Basrah, Iraq.
AB  - One hundred and forty-three swabs from diseased mouths and 271 from healthy
      controls were examined by direct wet smear method for Trichomonas tenax. Negative
      swabs were cultured on suitable media. The frequency of trichomonas tenax was
      8.4% and 4.1% in diseased and controls respectively. Of 23 positive samples, 14
      (3.3%) were positive on direct wet smear method and 9 (2.1%) were positive on
      culture method. There were 12 males and 11 females. Highest frequency of
      infection (6.7%) was found in 6-10 years age group and lowest (3.7%) in 11-20
      years group. Only 1% university students were positive.

PMID- 8133640
TI  - Severe bone marrow suppression in a patient with rheumatoid arthritis on
      methotrexate.

PMID- 8133641
TI  - Radioimmunoassay: principle and technique.

PMID- 8133642
TI  - Practical epidemiology and biostatistics in research. III. Rates.

PMID- 8133643
TI  - Proceedings of the 70th Annual Meeting of The Physiological Society of Japan.
      Yamanashi, April 1-3, 1993.

PMID- 8133644
TI  - Who meets the special health care needs of North Carolina schoolchildren?
AB  - In January 1991, 135 school districts and six specialty schools in North Carolina
      were surveyed to obtain data regarding the performance of specific health-related
      procedures in the school setting. Results indicate a patchwork approach to
      meeting the special health care needs of these children, and that a variety of
      school personnel as well as parents and health professionals are involved in
      coordinating and performing the procedures. Teachers and teacher assistants
      perform these health-related procedures 44% of the time. Registered nurses
      coordinate the care, including assessment, care planning, and supervision to
      assure continued competence of the care provider and safety for the student less
      than 45% of the time. Some 13 school districts reported having no school nurse
      services. Efforts have begun to legislate a statewide policy with appropriations
      for a registered nurse to provide an initial evaluation of the student's needs,
      develop care plan, and provide ongoing supervision of services to assure that
      safe, appropriate care is being provided to all students with special health
      related needs in North Carolina.

PMID- 8133645
TI  - Comparison of health risk behaviors between students in a regular high school and
      students in an alternative high school.
AB  - Prevalence of selected health risk behaviors of students attending an alternative
      high school (AHS) designed as a dropout prevention/dropout recovery high school
      was determined using the Youth Risk Behavior Survey. The survey also was
      administered to a sample of students attending a regular high school (RHS) in the
      same school district. A larger percentage of AHS students reported being involved
      in a physical fight the past year, having smoked at least one cigarette the past
      month, having drunk at least one drink on five or more occasions the past month,
      having drunk five or more drinks at least once the past month, having smoked
      marijuana at least once the past month, having used cocaine at least once the
      past month, and having ever had sexual intercourse. Results indicate a need for
      comprehensive health education/intervention programs to address the needs of
      youth in alternative school settings.

PMID- 8133646
TI  - Potential bias in teacher referrals to the school nurse.
AB  - Education literature suggests gender, race, and socioeconomic status of students
      influence the quality and quantity of interactions with their teachers. Studies
      show that teachers favor White, male, and upper-income children. This preliminary
      study was conducted to determine if bias was evident in teacher referrals to the
      school nurse. Referrals from seven elementary schools were studied. The 117
      children referred for nonroutine nursing intervention during the nine-week period
      were compared with 3,787 children not referred. Results showed no differences by
      gender, but significant differences occurred by socioeconomic status and race (p
      < .001). When controlling for gender and race, no differences existed between
      White males and African American males. However, significantly (p < .001) more
      African American females were referred than White females.

PMID- 8133647
TI  - School-age pregnancy: why hasn't prevention worked?

PMID- 8133648
TI  - Operation Meningo: public health nurses' role in Canada's largest mass
      immunization program.

PMID- 8133649
TI  - Violence-related attitudes and behaviors of high school students--New York City,
      1992.

PMID- 8133650
TI  - Antitrichomonal action of emodin in mice.
AB  - Emodin, an active component contained in the root and rhizome of Rheum palmatum
      L. (Polygonaceae), was found to have an inhibitory effect on the pathogenicity of
      Trichomonas vaginalis in mice. Emodin delayed the development of subcutaneous
      abscesses due to infection of this parasite. Also, it cures the intravaginal
      infection of trichomonads through oral administration. In cell cultures, it
      reduced the cytotoxic effect of this parasite towards mammalian cells. This
      inhibition was markedly reversed by the coexistence of free radical scavengers,
      indicating the possible mediation of free radicals.

PMID- 8133651
TI  - Fermentation in traditional medicine: the impact of Woodfordia fruticosa flowers
      on the immunomodulatory activity, and the alcohol and sugar contents of Nimba
      arishta.
AB  - The impact of Woodfordia fruticosa flowers on the immunomodulatory activity, and
      alcohol and sugar contents of the ayurvedic drug 'Nimba arishta' was investigated
      by means of model preparations. The use of Woodfordia flowers in model
      preparations resulted in a substantial increase of the inhibition of both human
      complement activity and chemiluminescence generated by zymosan-stimulated human
      polymorphonuclear leukocytes. It was established that the increased biological
      activity was not due to microbial interference, but to immuno-active constituents
      released from the Woodfordia flowers. It was also found that the flowers
      themselves are not the source of alcohol-producing microorganisms. Experiments
      performed with yeasts isolated from commercial Nimba arishtas showed, in
      agreement with empirical findings, significantly raised alcohol content upon
      addition of Woodfordia. An invertase activity exhibited by Woodfordia flowers may
      be causative of this effect.

PMID- 8133652
TI  - Antimicrobial activity of Dalbergia melanoxylon extracts.
AB  - The antibacterial and antifungal properties of the methanol, citric acid,
      aqueous, dichloromethane and petroleum ether extracts from the bark of Dalbergia
      melanoxylon were determined by using seeded agar plates with wells into which
      were placed the extract, and flasks of yeast extract and sucrose broth for
      mycelial growth of the fungi. After incubation for 24 h, the diameter of the
      inhibition zone was measured for the antibacterial tests and after 7 days, the
      dry weight of the mycelia was measured and a percentage of inhibition calculated
      using controls where no extracts were added. The results obtained showed that the
      citric acid extract exhibited strongest antimicrobial activity. The ethanol
      fraction showed significant antibacterial activity but was not significantly
      active against fungi. The dichloromethane extract exhibited no activity against
      bacteria but showed notable activity against fungi. The petroleum ether fraction
      showed no antimicrobial activity.

PMID- 8133653
TI  - Andrographolide protects rat hepatocytes against paracetamol-induced damage.
AB  - Andrographolide, the active constituent isolated from the plant Andrographis
      paniculata, showed a significant dose dependent (0.75-12 mg/kg p.o. x 7)
      protective activity against paracetamol-induced toxicity on ex vivo preparation
      of isolated rat hepatocytes. It significantly increased the percent viability of
      the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It
      completely antagonized the toxic effects of paracetamol on certain enzymes (GOT,
      GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells.
      Andrographolide was found to be more potent than silymarin, a standard
      hepatoprotective agent.

PMID- 8133654
TI  - Antifungal activities of crude extracts of Mitracarpus villosus (Rubiaceae).
AB  - Extracts of Mitracarpus villosus leaves and inflorescences were investigated
      individually for in vitro antifungal activities by agar-diffusion and tube
      dilution techniques. Ethanolic extracts produced definite antifungal activities
      against Trichophyton rubrum, Microsporum gypseum, Candida albicans, Aspergillus
      niger and Fusarium solani. The aqueous extracts and the glycerol vehicle control
      did not inhibit any of the fungi tested. The zones of inhibition produced by the
      ethanol extracts ranged from 10 to 20.5 mm while ketoconazole control ranged from
      9 to 19 mm. The minimum inhibitory concentration of the extracts ranged from 0.50
      to 4.0 mg/ml while their minimum fungicidal concentration values ranged from 1 to
      8 mg/ml. These results indicate that the extracts were fungistatic at lower
      concentrations and fungicidal at higher concentrations.

PMID- 8133655
TI  - Pharmacological studies on Aristolochia papillaris Mast. (Aristolochiaceae).
AB  - The non-specific and reversible smooth muscle relaxant activities of the
      ethanolic extract (EE) of Aristolochia papillaris Mast., a fraction of EE
      containing tertiary alkaloids (TAF) and of 3 compounds isolated from TAF are
      reported. In the non-pregnant rat uterus, EE and TAF inhibited both the oxytocin
      induced contractions and the amplitude of rhythmic spontaneous contractions. The
      IC50 values for EE and TAF were 0.91 and 0.22 microgram/ml, respectively in the
      first experiments while the corresponding values were 1.0 and 0.17 microgram/ml
      in the second case. The rhythmic contractions of the uterus obtained from 21-day
      pregnant rats were also reduced by EE and TAF with IC50 values of 25.5 and 11.2
      micrograms/ml, respectively. The relaxation of isolated guinea pig trachea
      produced by EE and TAF were also observed with the compounds moupinamide,
      coclaurine and isoboldine isolated from TAF. The IC50 values of these compounds
      were 1.58 x 10(-4) M, 3.98 x 10(-4) M and 7.10 x 10(-4) M, respectively.
      Propranolol significantly antagonized the effects of coclaurine and isoboldine
      but failed to inhibit the responses to moupinamide which suggests that the plant
      constituents produce muscle relaxation by beta-adrenoceptor-dependent and 
      independent mechanisms.

PMID- 8133656
TI  - Medicinal plant inventory of Kuna Indians: Part 1.
AB  - Results of an ethnopharmacognostic survey of 90 plants used by the Kuna Indians
      of San Blas Islands, who live in Ailigandi, are listed. Results of a literature
      search are also reported, including medical uses, known constituents and
      pharmacological effects.

PMID- 8133657
TI  - Determination of left ventricular mass by echocardiography in a normal
      population: effect of age and sex in addition to body size.
AB  - OBJECTIVE: In this study, we determined the effect of age, sex, and body size on
      left ventricular mass. DESIGN: Two-dimensional-guided M-mode echocardiography was
      used in an assessment of 111 healthy, normal adults. MATERIAL AND METHODS: Left
      ventricular mass was calculated with the cube function formula corrected by a
      regression equation to agree with autopsy estimates of left ventricular mass.
      Calculated left ventricular mass, indexed by body surface area and by height, was
      analyzed on the basis of sex and age of the study participants. Age was analyzed
      as a dichotomous, trichotomous, and continuous variable. The effects of age, sex,
      and obesity, as well as interactions, were tested within a multiple linear
      regression model framework. RESULTS: Left ventricular mass, when indexed for
      either body surface area or height, was greater in men than in women. For women,
      but not men, we found a small but significant increase in left ventricular mass
      with advancing age. Body mass index, an indicator of obesity, increased with
      aging in women but not in men and affected left ventricular mass. No significant
      changes were noted in left ventricular cavity size with advancing age, and the
      increase in left ventricular mass in women was due to increased ventricular wall
      thickness. CONCLUSION: The findings in this study suggest that left ventricular
      mass, as assessed by two-dimensional-guided M-mode echocardiography, is affected
      not only by sex and body size but also by age in women. This phenomenon may be
      related to an increase in body mass index with advancing age in women. In
      clinical studies that use echocardiographic left ventricular mass to diagnose
      left ventricular hypertrophy, these observations should be considered.

PMID- 8133658
TI  - Effects of age on left ventricular dimensions and filling dynamics in 117 normal
      persons.
AB  - OBJECTIVE: To determine standard left ventricular Doppler measurements in a large
      reference group of various ages to reflect the senescence process. DESIGN: We
      prospectively studied the influence of aging on left ventricular diastolic
      filling by performing Doppler echocardiography in 117 normal healthy volunteers.
      MATERIAL AND METHODS: Transthoracic pulsed-wave Doppler echocardiographic studies
      of pulmonary venous flow and left ventricular inflow were done in the 53 male and
      64 female study subjects. For analysis, the study subjects were arbitrarily
      classified into two groups: those younger than 50 years of age (group 1; N = 61)
      and those 50 years old or older (group 2; N = 56). RESULTS: A striking difference
      was found in pulmonary venous flow and left ventricular inflow between group 1
      and group 2 subjects. Group 2 had increased pulmonary venous peak systolic flow
      velocity (71 +/- 9 versus 48 +/- 9 cm/s), decreased peak diastolic flow velocity
      (38 +/- 9 versus 50 +/- 10 cm/s), increased peak atrial reversal flow velocity
      (23 +/- 4 versus 19 +/- 4 cm/s), and increased percentage of forward flow in
      systole (65 +/- 7 versus 55 +/- 8%) in comparison with group 1. In group 2, peak
      early filling velocity (62 +/- 14 versus 72 +/- 14 cm/s) and ratio of early
      filling to atrial filling (1.1 +/- 0.3 versus 1.9 +/- 0.6) were lower and peak
      atrial filling velocity (59 +/- 14 versus 40 +/- 10 cm/s) was higher than in
      group 1. Deceleration time (210 +/- 36 versus 179 +/- 20 ms) and isovolumic
      relaxation time (90 +/- 17 versus 76 +/- 11 ms) were prolonged in group 2 in
      comparison with group 1. CONCLUSION: This study confirms the major influence of
      the aging process on left ventricular diastolic function in a large series of
      normal subjects. This physiologic factor should be considered in Doppler
      assessment of left ventricular diastolic filling in future studies.

PMID- 8133659
TI  - Nutritional support for liver transplantation: identifying caloric and protein
      requirements.
AB  - OBJECTIVE: To characterize the caloric and protein requirements of patients with
      end-stage liver disease before and for 28 days after liver transplantation.
      DESIGN: We prospectively assessed 16 adult patients who were scheduled to undergo
      liver transplantation between December 1989 and September 1990. MATERIAL AND
      METHODS: Nitrogen balance, 24-hour urinary creatinine, 3-methylhistidine, and
      resting energy expenditure were determined before transplantation and on days 1,
      3, 5, 14, and 28 after transplantation. The investigators were unaware of the
      results of these measurements, and patients were fed in accordance with a
      previously established clinical protocol. RESULTS: Resting energy expenditure did
      not increase from preoperative values; however, urinary nitrogen and 3
      methylhistidine increased significantly after liver transplantation, an
      indication of protein catabolism from a myofibrillar source. A negative nitrogen
      balance persisted for 28 days post-operatively. CONCLUSION: We recommend that
      caloric intake be determined by using the formulation provided by the Harris
      Benedict equation at ideal body weight plus 20%. We also recommend that intake of
      protein be adjusted on the basis of preoperative nutritional assessment,
      perioperative hepatic and renal function, and results of tests used to measure
      the adequacy of administered protein. Parenterally or enterally administered
      protein of more than 1.2 g/kg daily should be well tolerated in most patients who
      have undergone liver transplantation.

PMID- 8133660
TI  - Effects of systemic delivery of insulin on plasma lipids and lipoprotein
      concentrations in pancreas transplant recipients.
AB  - OBJECTIVE: To determine whether pancreas transplantation alters lipid and
      lipoprotein concentrations and whether peripheral hyperinsulinemia is always
      associated with altered lipid levels. DESIGN: We assessed the lipid profiles of
      seven pancreas-kidney recipients with insulin-dependent diabetes mellitus, seven
      kidney recipients without diabetes who received the same immunosuppressive
      agents, and eight normal subjects. MATERIAL AND METHODS: In the three study
      groups, fasting and postprandial plasma glucose, insulin, C-peptide, cholesterol,
      triglyceride, free fatty acid, and apolipoprotein A-I, A-II, C-II, and C-III
      concentrations were determined. RESULTS: Fasting and postprandial glucose
      concentrations did not differ between the two transplant groups; however,
      peripheral insulin concentrations were twice as high (P < 0.05) in the pancreas
      kidney recipients as in the kidney recipients both before (102 +/- 15 versus 53
      +/- 6 pmol/L) and after (123 +/- 22 versus 61 +/- 6 nmol/L per 6 hours) ingestion
      of a meal. Preprandial and postprandial insulin levels in both transplant groups
      also were greater (P < 0.05) than those in normal subjects (35 +/- 6 pmol/L and
      40 +/- 7 nmol/L per 6 hours, respectively). Despite significant differences in
      insulin concentrations, no differences were noted in total cholesterol, high
      density or low-density lipoprotein cholesterol, plasma free fatty acids, or
      apolipoprotein A-I, A-II, C-II, and C-III concentrations among the study groups.
      Plasma triglyceride concentrations in the two transplant groups were similar (114
      +/- 20 versus 142 +/- 18 mg/dL) and were slightly more than those in the normal
      subjects (80 +/- 7 mg/dL). CONCLUSION: Despite peripheral hyperinsulinemia,
      pancreas transplantation can result in normal or near-normal lipid and
      lipoprotein concentrations. Thus, systemic delivery of insulin does not
      invariably produce an atherogenic lipid profile.

PMID- 8133661
TI  - Hemoglobin Denver [alpha 2 beta 2(41) (C7) Phe-->Ser]: a low-O2-affinity variant
      associated with chronic cyanosis and anemia.
AB  - OBJECTIVE: To report a previously undescribed low-O2-affinity hemoglobin variant
      that is associated with chronic cyanosis. DESIGN: Pertinent laboratory and
      historical data for the index case (from Denver, Colorado) and certain family
      members were recorded, and the hemoglobin variant was characterized. MATERIAL AND
      METHODS: Electrophoresis, high-performance liquid chromatography (HPLC), and
      isoelectric focusing were used to examine blood specimens for the presence of
      hemoglobin variants, and the O2 affinity of whole blood was determined. The
      abnormal peptide detected on reverse-phase HPLC of separated globin chains was
      analyzed for its amino acid composition and sequence. RESULTS: Although no
      abnormal hemoglobin band separated from hemoglobin A on electrophoresis, HPLC,
      and isoelectric focusing, a heat test showed hemoglobin instability, and O2
      affinity studies disclosed an appreciably right-shifted dissociation curve. On
      chromatography, the new variant--hemoglobin Denver--was found to be due to a
      substitution of serine for phenylalanine at position 41 (C7) in the beta chain.
      In addition to substantial reduction in O2 affinity, hemoglobin Denver is
      accompanied by moderate reticulocytosis and mild anemia. CONCLUSION: Hemoglobin
      Denver causes no clinical symptoms other than cyanosis, which is attributable to
      the low O2 affinity.

PMID- 8133663
TI  - The changing face of disorders of fatty acid oxidation.
AB  - OBJECTIVE: To review the current understanding of the rapidly changing field of
      disorders of fatty acid metabolism and to discuss the future directions for
      research. DESIGN: A literature review of the basic biochemistry of the beta
      oxidation pathway and clinical cases of defects of fatty acid metabolism are
      presented, and the diagnosis and treatment of such defects are discussed.
      MATERIAL AND METHODS: In many cases, a correct diagnosis will be made only if
      these disorders are specifically considered and appropriate tests are obtained,
      because results of screening tests for other organic acidemias are often normal
      in these entities. RESULTS: The first disorder of fatty acid metabolism was
      described only 20 years ago. Since then, at least 15 different inborn errors of
      metabolism that affect beta-oxidation have been identified, most in the past 10
      years. Within the past 5 years, investigators have realized that a deficiency of
      one of these enzymes, medium-chain acyl coenzyme A dehydrogenase, may be one of
      the most common inborn errors of metabolism. This disorder may have a frequency
      equal to that of phenylketonuria in some populations in the United States and
      northern Europe. Approximately 1 to 3% of all unexplained deaths during infancy
      and childhood are probably related to disorders of beta-oxidation. Diagnosis of
      these disorders can be difficult because of the intermittent nature of the
      excretion of characteristic compounds. The mainstay of therapy for defects of
      beta-oxidation is avoidance of fasting. CONCLUSION: All patients with a suspected
      defect of fatty acid metabolism should be assessed and monitored by a specialist
      trained in the care of such patients. Continued improvements in the ability to
      diagnose and treat these disorders will be directly linked to new advances in the
      basic research on these enzymes. Movements to screen newborns for medium-chain
      acyl coenzyme A dehydrogenase are under way in some medical centers. Proposed
      tests include metabolite analysis or direct mutation analysis (or both) from
      blood spots from newborn screening cards already obtained for every newborn in
      the United States.

PMID- 8133662
TI  - Obstructive sleep apnea manifesting as suspected angina: report of three cases.
AB  - OBJECTIVE: To describe three cases of obstructive sleep apnea that resembled
      coronary artery disease and to suggest features that might distinguish these two
      syndromes. DESIGN: We present three detailed case reports of patients with severe
      obstructive sleep apnea and discuss similar cases from the literature. MATERIAL
      AND METHODS: Two obese women and one obese man with previously undiagnosed
      obstructive sleep apnea had chest discomfort, episodic dyspnea, and palpitations,
      most prominent at night. All three patients had multiple cardiac risk factors and
      had previously undergone cardiac evaluations, including at least two prior
      cardiac catheterizations each. Repeated cardiac catheterization revealed less
      coronary occlusive disease than expected on the basis of the symptoms in all
      three patients and a small atrial septal defect in one patient. When reassessed,
      the medical histories suggested obstructive sleep apnea. RESULTS: Overnight
      polysomnography documented the presence of severe sleep apnea; the three patients
      had mean values of 56 disordered breathing events per hour and 44% minimal oxygen
      saturation. Although bi-level or continuous positive airway pressure yielded
      initial improvement, all patients had difficulty with routine use of this therapy
      after 1 1/2 years of follow-up. CONCLUSION: The initial manifestations of severe
      obstructive sleep apnea may simulate angina, suggest arrhythmia, or mimic heart
      failure. Failure to inquire about snoring and daytime somnolence in patients with
      chest pain may prevent the identification of clinically significant disordered
      breathing during sleep.

PMID- 8133664
TI  - Multiple myocardial hamartomas causing ventricular tachycardia in young children:
      combined surgical modification and medical treatment.
AB  - OBJECTIVE: To describe two cases of incessant ventricular tachycardia caused by
      multiple myocardial hamartomas. MATERIAL AND METHODS: Two infants, 13 and 14
      months old, who had had multiple episodes of symptomatic tachycardia were
      referred to our institution. Incessant ventricular tachycardia was diagnosed.
      Initially, the patients received pharmacologic therapy. The recurrent tachycardia
      resulted in notable hemodynamic instability. No structural abnormalities were
      detected on the echocardiograms. In one patient, an electrophysiologic study
      revealed that the site of ventricular ectopic beats was in the anterolateral wall
      of the left ventricle, midway between the apex and the base. In the other
      patient, a preoperative electrophysiologic study was not undertaken because of
      the inability to obtain central venous access. RESULTS: Diffuse hamartomas were
      found throughout the ventricular myocardium in both patients. Surgical resection
      and cryoablation of the lesions in combination with medical therapy helped
      control the tachyarrhythmia. At 7 and 17 months postoperatively, the patients
      were in normal sinus rhythm and were receiving medication. CONCLUSION: In young
      children who have incessant ventricular tachycardia but no lesion evident on
      echocardiography, angiography, or other imaging modalities, a myocardial tumor
      should be suspected, and pharmacologic therapy should be instituted. If the
      medical regimen fails, surgical intervention should be undertaken, directed at
      areas localized by inspection and by preoperative and intraoperative
      electrophysiologic studies.

PMID- 8133665
TI  - Herpes simplex infection causing acute necrotizing tonsillitis.
AB  - OBJECTIVE: To describe the clinical and pathologic features of acute herpetic
      tonsillitis and to compare the histologic findings with those of herpetic
      lymphadenitis. DESIGN: We present a case report of a 22-year-old woman with
      bilateral cervical adenopathy, acute tonsillitis, and suspected peritonsillar
      abscess. MATERIAL AND METHODS: Histologic examination of the excised tonsils
      demonstrated discrete necrotic areas that contained cells with intranuclear viral
      inclusions. RESULTS: The diagnosis of herpetic tonsillitis was confirmed by
      demonstrating herpes simplex virus (HSV)-infected cells on paraffin section
      immunostains and by positive HSV cultures of the tonsillar tissue. CONCLUSION:
      HSV infection is an uncommon cause of acute tonsillitis; the histologic findings
      are similar to those seen in herpes simplex lymphadenitis.

PMID- 8133666
TI  - Endovascular treatment of intracranial aneurysms.
AB  - OBJECTIVE: To examine the techniques, reported experiences, and advantages and
      disadvantages associated with the endovascular treatment of intracranial
      aneurysms. DESIGN: We review the endovascular techniques used for the treatment
      of intracranial aneurysms and the sequelae of subarachnoid hemorrhage, which have
      evolved during the past 10 years. MATERIAL AND METHODS: Two broad categories of
      endovascular therapy for intracranial aneurysms are described: occlusion of the
      parent artery and preservation of the parent artery by selective occlusion of the
      aneurysm with balloons or metallic coils. The Mayo protocol for testing tolerance
      of patients before permanent balloon occlusion of the parent artery is described,
      as are the types of aneurysms most amenable to this treatment. In addition, use
      of balloon angioplasty for cerebral vasospasm after subarachnoid hemorrhage is
      reviewed. RESULTS: Recent improvements in microcatheter technology have
      facilitated the safe navigation of percutaneously introduced catheters in the
      intracranial circulation and selective catheterization of intracranial aneurysms.
      Surgically difficult aneurysms are now being treated with endovascular techniques
      more frequently than in the past. Early results from animal experiments and human
      trials have shown that selective occlusion of aneurysms with metallic coils may
      have a role in the treatment of intracranial aneurysms. Balloon angioplasty of
      symptomatic cerebral vasospasm has demonstrated improvement in neurologic
      function in approximately 70% of patients. CONCLUSION: As technology continues to
      improve and as greater experience is obtained, interventional neuroradiologists
      will continue to have an increasingly important role in the treatment of
      intracranial aneurysms.

PMID- 8133667
TI  - Sir Alan Hodgkin--Nobel Prize winner for nerve transmission.

PMID- 8133668
TI  - Erroneous arterial placement of a central venous catheter.

PMID- 8133669
TI  - Porphyrias: clinical evaluation and interpretation of laboratory tests.

PMID- 8133670
TI  - Echocardiographic assessment of left ventricular mass--what more can we learn?

PMID- 8133671
TI  - Three-dimensional echocardiography: use of additional spatial data for measuring
      left ventricular mass.

PMID- 8133672
TI  - Aspiration pneumonia caused by Mycobacterium smegmatis.

PMID- 8133673
TI  - Tuberculosis.

PMID- 8133674
TI  - Stimulus-secretion coupling and insulin secretion in aging: evaluation of glucose
      oxidation and ATP-sensitive potassium channel responsiveness.
AB  - The purpose of this study was to evaluate possible age-related alterations in the
      glucose-stimulus/insulin-secretion coupling mechanism of islets of Langerhans. To
      this end, the interaction among insulin secretion, glucose oxidation, and ATP
      sensitive potassium (K ATP) channel responsiveness was determined in islets of
      Langerhans isolated from 6-, 12-, and 26-month-old male Fischer 344 (F344) rats.
      Groups of 20 islets were incubated for 40 min at 37 degrees C in a buffer
      containing: (1) either 1.7 or 11.1 mM glucose; (2) 1.2 microM glyburide and
      either 1.7 or 11.1 mM glucose; (3) 5 microM epinephrine and 11.1 mM glucose; or
      (4) 1.2 microM glyburide, 5 microM epinephrine, and either 1.7 or 11.1 mM
      glucose. Insulin release of islets incubated in the presence of glyburide and 1.7
      or 11.1 mM glucose was greater than that of islets incubated in glucose alone,
      while glucose oxidation did not increase. Epinephrine inhibited insulin release
      and glucose oxidation at 11.1 mM glucose and abolished glyburide-enhanced insulin
      release at 11.1 mM glucose. No effect of age was observed in any of the treatment
      categories. These results indicate that if age-related alterations are occurring
      in glucose-stimulus/insulin-secretion coupling, then such alterations are not
      associated with changes in K ATP channel-mediated responsiveness.

PMID- 8133675
TI  - Decreased accumulation of beta 1-adrenergic receptor, G alpha s and total myosin
      heavy chain messenger RNAs in the left ventricle of senescent rat heart.
AB  - The expression of genes coding for the beta 1-adrenergic receptor (beta 1-AR),
      the alpha subunit of Gs and total myosin heavy chain (MHC) was compared between
      left ventricles (LV's) from young (6-7 weeks old) and old (22 months old) rats.
      The mRNA levels were quantitated by Northern or Slot blots analyses using
      specific DNA probes. Ageing was found to be associated with a reduction in beta 1
      AR (77%), G alpha s (33%) and, total MHC (51%) mRNA levels with no concomitant
      change in 18S RNA and poly(A+) mRNA levels. These results indicate that
      transcriptional and/or post-transcriptional mechanisms participate in the control
      of beta-adrenergic receptor density during ageing. As in the senescent LV, beta 1
      AR mRNA level is reduced in the hypertrophied LV, whereas the level of G alpha s
      mRNA is reduced in the senescent but not in the hypertrophied LV. From our data
      we conclude (1) that a dual mechanism may operate during ageing, mechanical
      factors indirectly regulating beta 1-AR mRNA level, while changes in G alpha s
      mRNA level do not depend on hemodynamic load and (2) that the re-expression of
      beta-MHC mRNA does not compensate for the decreased accumulation of alpha-MHC
      mRNA which results in a large decrease in the level of total MHC mRNA in the
      senescent LV.

PMID- 8133676
TI  - Changes in the fatty acid composition of stored erythrocytes from sheep of
      different ages.
AB  - This study examined the profile in sheep erythrocyte fatty acids from animals of
      different ages during storage at 4 degrees C in a nutritive medium for up to 6
      days. The changes found in the fatty acyl profile were a decrease (P < 0.01) in
      the percentage of arachidonic acid and an increase (P < 0.01) in the percentage
      of minor fatty acids (representing < 2% in each case; 20:2, 22:0 and 22:1) with
      respect to fresh erythrocytes in all age groups. However, the
      saturated/unsaturated ratios and unsaturated index started almost constant in all
      cases. The changes observed occurred after 24-48 h of storage, with significant
      increases (P < 0.01) in the fluorescence detected in the lipid extracts from
      stored erythrocytes during this period. The above findings suggest peroxidative
      damage and changes in the erythrocyte lipid membrane during storage.

PMID- 8133677
TI  - Differential effect of host microenvironment and systemic humoral factors on the
      implantation and the growth rate of metastatic tumor in parabiotic mice
      constructed between young and old mice.
AB  - B16 melanoma cells were injected into the tail vein of young mice, old mice and
      parabiotic mice constructed between young and old mice, and the number and shape
      of pulmonary metastases were compared among three experimental groups. In
      unpaired mice, the number of metastatic colonies in the lungs was 10-fold larger
      in young than in old mice. In parabiotic mice, the number in young mice was
      almost comparable with that of unpaired young mice, but the number in old mice
      approached the level of young mice. Metastatic colonies on the pulmonary surface
      of young mice were mostly nodular in shape, while those of old mice were flat in
      shape. The shape of colonies reflecting the tumor growth rate did not change in
      parabiotic old mice in spite of an increase in number. In young parabiotic mice,
      the large and intermediate colonies decreased with a concomitant increase of
      small ones as compared with unpaired young mice. These results suggest that the
      implantation of metastatic colonies in the lung is mainly dependent on systemic
      humoral factors and their growth is mainly dependent on the host local factors in
      the microenvironment, and distinct age changes of both factors greatly influence
      the metastatic mode of tumors, respectively.

PMID- 8133678
TI  - [The influence of hygiene and cultural characteristics of the family environment
      on dietary patterns of school children].
AB  - BACKGROUND: The diet of school aged children constitutes one of the basic pillars
      on which the health of an individual may be placed. The influence of the parents
      in dietary habits of children is absolute. The aim of the present study was to
      analyze what hygienic-cultural aspects of the familial environment are most
      linked to the diet of school children. METHODS: A study of non paired cases and
      controls was carried out in 48 children of 6-7 years of age (cases) with maximum
      consumption of cold meats and minimum consumption of vegetables and lettuce
      (universe = 131 children) versus a double control group of 34 children with
      inverse dietary patterns and 83 children who did not fulfill inclusion criteria
      of cases. Personal cleanliness and washing habits, attitudes towards television
      viewing, parental consumption of cigarettes and alcohol and sex education were
      also analyzed. RESULTS: Multivariant analysis identified a smoking father as a
      risk factor of worse diet (OR = 3.3, p = 0.016), with sex education received at
      home being associated with a decrease of 70% in the probability of having a bad
      diet (OR = 0.3, p = 0.016) on using the restricted control group. The smoker
      father was the only circumstance associated to bad diet on including the
      remaining children of the universe as controls (OR = 2.6, p = 0.018).
      CONCLUSIONS: The diet of school children seems to be related with the global
      attitude of the family with regard to health. Smoking habit of the father may
      represent a negative marker of food preferences with regard to quality of diet.

PMID- 8133679
TI  - [Family environment, tobacco, and nutrition].

PMID- 8133680
TI  - [Anthropometry and obesity].

PMID- 8133681
TI  - [Report on hospital infection. General Subdirectorate of Services and Evaluation
      of Health Technologies].

PMID- 8133682
TI  - [Change patterns in the use of antibiotics in hospitals: basis and new
      perspectives].

PMID- 8133683
TI  - [Molecular genetics of pigmentary retinopathy].

PMID- 8133684
TI  - [Postpoliomyelitis progressive muscular atrophy].

PMID- 8133685
TI  - [Anthropometric reference parameters of the elderly population].

PMID- 8133686
TI  - [Phenomenon of complete inversion of the visual image in an episode of transient
      vertebrobasilar ischemia].

PMID- 8133687
TI  - [Mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and chronic
      hepatitis C. Sequential treatment with immunosuppressors and interferon].

PMID- 8133688
TI  - [Atrial myxoma associated with Streptococcus viridans bacteremia].

PMID- 8133689
TI  - [Transient typing disability or typing pseudodisability].

PMID- 8133690
TI  - [Vaccines against pneumococcus and Haemophilus influenzae, yes; "vaccine" against
      flu, no].

PMID- 8133691
TI  - [Antibiotic prophylaxis in surgery].

PMID- 8133692
TI  - [Use of digoxin in a population cared for in the emergency department].

PMID- 8133693
TI  - [Submandibular fold. An alternative for the assessment of subcutaneous fat].
AB  - BACKGROUND: Folds are a useful method of measuring subcutaneous fat. This study
      reports the feasibility of the use of the submandibular fold to evaluate the
      subcutaneous fat. METHODS: A transversal descriptive study was designed by a poly
      staged stratified randomized sample (n = 572). A series of anthropometric
      measurements (weight, height, different folds and surrounding areas) were
      performed in addition to the measurement of the submandibular fold. In addition
      blood pressure was determined as well as oral glucose tolerance test. RESULTS:
      After correction of the effect of age, the submandibular fold was found to be
      related with both the Quetelet's index (BMI) (males r = 0.50; females r = 0.61,
      both p < 0.0001) and the Benn's index (males r = 0.53; females r = 0.60, both p <
      0.0001). Their correlations with those of other folds and with the measurements
      of centralization place the submandibular fold in a median position with respect
      to central and peripheral fat deposits. Furthermore, the percentage of fat which
      the increase in BMI carries is practically constant. Likewise, it was associated
      with the presence of high blood pressure in both sexes (males F = 9.7, p < 0.025;
      females F = 6.1, p < 0.025), diabetes mellitus (F = 6.1, p < 0.005) and inguinal
      hernias (F = 10.8, p < 0.0025) in males and in females, as well as to the
      presence of abdominal striae in females (F = 12.2, p < 0.001). CONCLUSIONS: The
      submandibular fold may be used by investigators who wish to evaluate subcutaneous
      fat through one sole fold, which is accessible and easy to measure. This measure
      is intermediate between the central and peripheral zones. In addition, it may
      reflect the fat deposit which is produced with both an increase in the body mass
      index and age.

PMID- 8133695
TI  - [Isotopic renogram after captopril administration: clinical experience in the
      assessment of the hypertensive patient].
AB  - BACKGROUND: Isotopic renogram allows renal function to be estimated in both
      kidneys independently. The glomerular filtrate in ischemic kidneys is largely
      dependent on the tone of the efferent glomerular arteriolae and therefore on the
      concentration of circulating angiotensin II. METHODS: In 42 patients with severe
      high blood pressure in whom renal angiographic study was carried out for
      suspicion of vasculo-renal hypertension, an isotopic renogram using 99m Tc-DTPA
      as a tracer was performed in basal conditions and following the administration of
      50 mg of oral captopril. RESULTS: In 21 patients both the angiographic
      examination and the post-captopril renogram were normal. In 16 patients in whom
      uni or bilateral stenosis higher than 50% of the lumen of renal artery was
      observed on angiographic examination, the post-captopril renogram showed changes.
      In 5 patients the angiography was normal while the renogram showed evaluable
      changes. No false negatives were observed in the post-captopril renogram, however
      the basal renogram was not demonstrative in 6 patients with stenosis of the renal
      artery. Sensitivity of the test was thus 100% and specificity 80%. The positive
      predictive value was 76% and the negative predictive value 100%. CONCLUSIONS: The
      post-captopril renogram may be a useful test in the functional study of renal
      behaviour in patients with vasculo-renal hypertension.

PMID- 8133694
TI  - [Relationship of the renin-angiotensin-aldosterone system with auricular
      natriuretic factor in its response to the action of thiazide diuretics and to
      nifedipine, a sustained-release calcium antagonist].
AB  - BACKGROUND: Blood pressure (BP) response to diuretics may be considered as an
      index of salt-sensitivity. Salt-sensitive patients may have an enhanced response
      to calcium channel blockers. In this study we correlate the basal values of two
      of the hormonal systems involved in the control of Na balance comparing them with
      the antihypertensive effects of a calcium channel blocker and a diuretic, to
      assess if BP response depends of a particular hormonal pattern by which we could
      define salt-sensitive patients. METHODS: We studied 21 essential hypertensive
      patients in a lineal sequence in an open protocol, first treated with slow
      release nifedipine (Nif-30), 30 mg daily, as a single dose, for 30 days, followed
      by amiloride+hydrochlorothiazide (HCT+Am), 50 mg and 5 mg, daily, for another
      month. Plasma renin activity (PRA), plasma aldosterone (PAld) and 24 hours
      urinary aldosterone (UAld) and atrial natriuretic factor (ANF), were measured at
      the start and end of the study. The hormonal values on each group were compared
      and correlated with changes observed in BP at the end of each period of
      treatment. RESULTS: HCT+Am decreased median arterial pressure (MAP) from 121.4 +/
      11 to 110.4 +/- 8 mmHg and Nif-30 to 108.7 +/- 12.4 mmHg, both p < 0.0004. There
      were 76% controlling MAP with Nif-30 whereas 48% did so with HCT+Am, p < 0.01,
      HCT+Am also increased PRA, PAld and decreased ANF, Ca urinary excretion and
      plasma PTH. Nif-30 did not alter the renin-angiotensin-aldosterone system, nor
      ANF. PTH remained unchanged. The MAP decrement caused by HCT+Am depended on
      baseline BP, r = -0.69, p < 0.0005, whereas Nif-30 decreased MAP independent from
      its baseline values, r = -0.02, NS. PAld showed a reverse correlation with ANF
      after treatment, r = -0.43, p < 0.05. The decrease of MAP holds a reverse
      relationship with ANF, both with HCT+Am, r = -0.47, p < 0.02, and with Nif-30, r
      = -0.45, p < 0.04. CONCLUSIONS: Treatment with Nif-30 was superior to HCT+Am in
      number of patients controlled, but the decrease in MAP is similar. Since the
      antihypertensive response to diuretic therapy and to calcium channel-blockers is
      related to low levels of ANF this fact could indicate some sort of defect of ANF
      secretion.

PMID- 8133696
TI  - [Factors involved in the hypertensive patient non-compliance with treatment].
AB  - BACKGROUND: It is impossible to evaluate the therapeutic efficacy in hypertension
      without knowing the compliance of the treatment. The lack of compliance does not
      allow therapeutic efficacy to be achieved. This study evaluates possible factors
      involved in the non compliance of treatment in hypertensive patients and the
      characteristics defining the non compliant patient. METHODS: The control
      technique was tablet counting. The study was carried out in 157 hypertensive
      patients belonging to the Centro de Carrus (Elche-Alicante, Spain). RESULTS:
      53.3% of the sample were shown to follow the therapy. 45.2% of patients not
      fulfilling the treatment believed that they were doing it correctly. Non
      compliance was found to be associated to the following factors: hypertensive
      patients of older age (p = 0.0054), low cultural level (p = 0.0027), bad
      knowledge of the disease (p = 0.0166), recent or lengthy knowledge of the disease
      (p = 0.00677), presence of other associated chronic diseases (p = 0.003), bad
      control of blood pressure (p = 0.0108), receiving more than two drugs for
      treatment (p = 0.0071), carrying out more than two medication intakes per day (p
      = 0.00309), saying that the diet is not well followed (p = 0.0187) and performing
      other associated pharmacologic treatments (p = 0.0024). CONCLUSIONS: Non
      compliance is a very frequent fact in patients with hypertension. Knowledge and
      evaluation of the factors involved in non compliance allows identification and
      intervention in patients who do not take the medication.

PMID- 8133697
TI  - [Chronic neutropenia in the adult].

PMID- 8133698
TI  - [White coat hypertension].

PMID- 8133699
TI  - [Basic steps for the control of tuberculosis in a community].

PMID- 8133700
TI  - [Serotoninergic syndrome: a potentially fatal entity].

PMID- 8133701
TI  - [Right pneumococcal endocarditis. A not so severe disease].

PMID- 8133702
TI  - [Nephrotic syndrome in a patient infected with the human immunodeficiency virus].

PMID- 8133703
TI  - [Systemic lupus erythematosus and thrombotic thrombocytopenic purpura].

PMID- 8133704
TI  - [Paralysis associated with weight loss].

PMID- 8133705
TI  - [Acute renal failure secondary to sulfadiazine-induced crystalluria].

PMID- 8133706
TI  - [Standard error or confidence interval? Advantages of giving the confidence
      interval to present results to biomedical journals].

PMID- 8133707
TI  - [Hirsutism and virilization caused by the administration of topical
      testosterone].

PMID- 8133708
TI  - [Disseminated Langerhans-cell histiocytosis, with pulmonary, bone, and choroid
      involvement].

PMID- 8133709
TI  - [Human immunodeficiency virus type 2 infection in 2 seamen of the northwest of
      Spain].
AB  - The first two cases of HIV-2 infection in autoctonous Spanish subjects are
      presented. Two sailors (62 and 42 years of age) of Galician origin who travelled
      to east African countries are reported. The epidemiologic, clinico-evolutive
      characteristics--with manifestations similar to HIV-1 infection (oral candidiasis
      and villous leukoplasia)--, and therapeutic response to zidovudine are described.
      The risk of HIV-2 infection in sailors travelling to Africa and the absence of
      opportunistic infections in a period of at least 6 to 11 years following
      infection despite CD4+ lymphocytes being under 0.200 x 10(9)/l, are of note.

PMID- 8133710
TI  - [The use of national and foreign scientific information in Spanish medical
      journals: a new repertoire for its study].

PMID- 8133712
TI  - [What is and what is not Bartter syndrome?].

PMID- 8133711
TI  - [AIDS caused by HIV-2: the first case diagnosed in Spain].

PMID- 8133713
TI  - [Primary pulmonary hypertension in an HIV-positive pregnant woman].

PMID- 8133714
TI  - [Prognostic factors of non-Hodgkin's lymphoma in patients with human
      immunodeficiency virus infection].

PMID- 8133715
TI  - [External and institutional control of clinical research].

PMID- 8133716
TI  - [Mucose-associated lymphoid tissue gastric lymphoma associated with Evans
      syndrome].

PMID- 8133717
TI  - [Prophylaxis with ciprofloxacin in postchemotherapy neutropenia in acute myeloid
      leukemia].
AB  - BACKGROUND: Infection is the most frequent complication in patients with acute
      myeloid leukemia (AML) following chemotherapy. The new quinolones, among which
      ciprofloxacin may be found, seem to be effective in the prophylaxis of this
      complication. METHODS: Fifty consecutive episodes of neutropenia were studied in
      patients with AML who received prophylaxis with ciprofloxacin and these were
      compared with a historic control group of another 50 consecutive episodes of
      neutropenia in AML patients who did not receive antibiotic prophylaxis. The
      difference with regard to the prevalence of infection and the characteristics of
      the same were studied. RESULTS: Ciprofloxacin significantly decreased the number
      of febrile episodes following chemotherapy of induction or consolidation with
      respect to those who did not receive prophylaxis (68% versus 94%; p = 0.002).
      Likewise, the patients who received ciprofloxacin presented fewer
      bacteriologically documented infections (26% versus 50%; p = 0.023), bacteremias
      (10 versus 25, p = 0.03) and infections produced by Gram negative microorganisms
      (2 versus 13, p = 0.009). Ciprofloxacin led to disappearance of the infections
      produced by Pseudomonas aeruginosa. Delay in the development of infection was
      observed in patients who received ciprofloxacin (mean: 11 days, CI: 7-15 days)
      with respect to those who did not receive prophylaxis (mean: 6 days, CI: 4-6
      days) (p = 0.0001). CONCLUSIONS: Ciprofloxacin is an effective antibiotic in the
      prevention of infection in episodes of neutropenia after induction or
      consolidation chemotherapy in patients with acute myeloid leukemia. Not only does
      it decrease the number of febrile episodes, bacteriologically documented
      infections, bacteremias and infections produced by Gram negative microorganisms,
      but it also delays the appearance of the febrile episodes.

PMID- 8133718
TI  - [Effectiveness of hypercholesterolemia detection in high risk individuals
      compared to opportunistic detection].
AB  - BACKGROUND: The aims of this study were to estimate the number of people who
      should receive some intervention (pharmacologic and/or dietetic) to reduce
      cholesterol concentrations and to evaluate selective case finding in comparison
      to opportunistic detection. METHODS: Six hundred twenty-five individuals
      participating in a study of cardiovascular risk factors were included in the
      study. Those with total cholesterol concentrations (TC) greater than 6.2 mmol/l
      and those with CT concentrations greater than 5.2 mmol/l observed upon lipid
      profile analysis and history of cardiovascular disease and/or risk factors were
      considered as candidates. Out of these individuals, those with cholesterol
      concentrations linked to low density lipoproteins greater than 4.14 mmol/l or
      greater than 3.37 mmol/l and previous history of cardiovascular disease or two
      risk factors were considered candidates to undergo intervention to reduce
      cholesterol concentrations. Moreover, the number of individuals with CT
      concentrations greater than 6.2 mmol/l which would not be detected if CT was only
      determined in those who already had another cardiovascular risk factor was
      estimated. RESULTS: 37.5% (CI 95%; 33.8%-41.5%) of the individuals required lipid
      profile and out of these 88.8% (CI 95%; 3.8%-92.4%) were candidates to receive
      intervention. Upon evaluating the efficacy of the strategy of selective case
      finding it was observed that the sensitivities of the risk factors were low,
      ranging from 22.6% in those with family history of cardiovascular disease to
      34.8% in cases with personal history of high blood pressure. CONCLUSIONS: If
      selective case finding of high risk subjects was the only strategy applied, many
      individuals with hypercholesterolemia would remain undetected, therefore the
      strategy of opportunistic detection is preferable whenever possible.

PMID- 8133719
TI  - [Adaptation of a measure of dysfunction-related illness: the Spanish version of
      Sickness Impact Profile].
AB  - BACKGROUND: The aim of the research was to adapt the Sickness Impact Profile
      (SIP) for their use in Spain. The Sickness Impact Profile is a questionnaire that
      measure the dysfunction related illness in 12 categories. It contain 136 items
      weighted by the relative importance in each category. In the present article we
      described the translation and the preliminary weighting process of each item and
      category. METHODS: In the translation we used the back-translation method by
      means of English-American and Spanish bilinguals. The items with equivalence B or
      C were discussed with a group of patients until to reach an agreement in the
      version. The scaling was carried out by 25 judges (health professionals).
      Following the same methodology as the original version, the judges firstly placed
      the relative values of each item in each category on an interval scale of 1
      (minimal dysfunction) to 11 (maximal dysfunction) points; secondly the items most
      and least dysfunctional in each category were placed on a 1-15 interval scale
      (method of equal appearing intervals). RESULTS: In the translation process we
      identify 12 items with equivalence B or C. The results showed a high correlation
      between the values obtained by each judge and the mean values of the judges by
      item (0.64-0.81). The items were rated with a standard deviation of the mean of
      1.91 and a standard deviation of the standard deviation of 0.52. The correlation
      between Spanish and American values was r = 0.84 (p < 0.001). CONCLUSIONS: Given
      the low number of non-equivalent items, the high agreement among the judges in
      the valuation of the items and the high correlations obtained between the Spanish
      and American weights, we conclude that the cross-cultural process have been
      satisfactory. The results should be to repeat in a sample of health consumers.
      The process of adaptation of the Spanish version will not finish until that the
      validity and reliability are similar to those of the original version.

PMID- 8133720
TI  - [HTLV-II].

PMID- 8133721
TI  - [Transmission of resistance to Mycobacterium tuberculosis in HIV-infected
      subjects. The so-called third HIV outbreak].

PMID- 8133722
TI  - [Generalized anxiety disorder. Clinical and nosological remarks].
AB  - The authors review current understanding of generalized anxiety disorder, with
      particular regard to the clinical description made by the DSM-III-R. Discussion
      is focused on the validity of the diagnostic criteria of the disorder and on the
      debate on the nosological position of the illness. The review cites evidence
      regarding prevalence of the disorder and data on its comorbidity with the other
      anxiety disorders and with mood disorders. Evidence on intra-episodic,
      longitudinal and familial co-morbidities are assessed. Aspects of psychopathology
      of generalized anxiety disorders are also discussed.

PMID- 8133723
TI  - [Childhood trauma and personality disorders].
AB  - The influence of the model of object relations on modern psychodynamic research
      has led to increased emphasis on the importance of relations and traumatic events
      in the genesis of some psychic disorders, especially with regard to personality
      disorders. The development of axis II in the DSM-III system has increased the
      number of empiric studies in this field. In this paper, the Authors report data
      relating to a sample of 49 subjects with personality disorders (DSM-III-R) in
      which the presence of sexual abuse, physical maltreatment and negative family
      atmosphere was examined using a self-administered questionnaire (CAT). The
      results suggest a significant presence of these events throughout the sample and
      reveal a correlation between some personality disorders and specific traumatic
      events. It may therefore be hypothesized that the presence of these events
      represents an important factor from the point of treatment, both in technical and
      in prognostic terms.

PMID- 8133724
TI  - [Psychogenic eating disorders and the family set-up].
AB  - The paper examines the position of dysorexic patients within the family set-up, a
      topic on with until now attention has not been focused, in order to highlight the
      latter's possible importance since it has been overlooked in favour of the
      situation of the "fusion family" in which parent-child relations are predominant.
      The paper underlines the frequency of a subordinate position in relation to
      "strong" older brothers or sisters. There is no possibility of compensating this
      feeling of inferiority which therefore conditions the choice of a fictitious
      goal: regressive and guilty gratification in bulimia and hypecontrol of the body
      in anorexia.

PMID- 8133725
TI  - [Acute psychosis. Clinical contribution].
AB  - In a vast survey of clinical cases Authors have considered 50 specific cases of
      acute psychosis corresponding to the following criteria: first stage, lack of
      organic and caused by drugs disorders, lack of visible affective symptoms.
      Different social and personal situations have been considered as well as the
      initial symptoms and the characteristics of the clinical picture. These
      variations have been correlated to the result and the course of the illness and
      attention has been drawn to the importance of adaptation before illness, presence
      of stress elements, very acute initial symptoms, oneiric characteristics of the
      clinical picture on the positive course. In a further diagnosis only 20 of these
      cases can be attributed to the schizophreniform disorder and among these 20 the
      majority develop with relapses, consequences and emotional damages.

PMID- 8133726
TI  - [Antisocial personality disturbance and sex offense. Psychodynamic, clinical and
      psychiatric-forensic considerations in a clinical case].
AB  - In this paper the authors suggest a new psychodynamic and clinical interpretation
      of Antisocial Personality Disturbance. Starting from an emblematic clinical case,
      the consequent psychiatric-forensic considerations aim at a valuation of
      imputability about sex offenders affected by this Disturbance.

PMID- 8133727
TI  - [Psychiatry in the Bible].

PMID- 8133728
TI  - Neuromechanics of the patellofemoral joint.
AB  - Patellofemoral joint pain is one of the most common ailments associated with
      visits to sports medicine clinics and can be disabling, although conservative
      clinical treatment has a reportedly very high success rate. Patellofemoral joint
      pain is often associated with improper tracking of the patella within the femoral
      trochlear notch. Improper tracking of the patella can be associated with
      increased patellofemoral contact pressures that may be a mechanical stimulus
      underlying patellar cartilage degeneration. In those cases in which anatomic
      anomalies and trauma may be excluded as the basis for improper tracking,
      attention is directed toward possible disruptions to the central nervous system
      control and contractile potential of the knee joint extensor musculature that
      underlies proper patellofemoral mechanics. This paper presents a review of three
      seminal components related to the neuromechanics of patellofemoral function;
      patellofemoral tracking, patellofemoral contact pressures, and neuromotor control
      of patellofemoral agonists. It is the intent of the authors to illuminate areas
      requiring further basic and clinical research and provide a point of departure
      for this work.

PMID- 8133729
TI  - Comparison of submaximal exercise responses using the Bruce vs modified Bruce
      protocols.
AB  - The purpose of this study was to determine whether the parameters commonly used
      to evaluate a training effect can be compared when serial tests are performed
      using different protocols. Thirty-two patients with stable coronary artery
      disease performed both the standard and modified Bruce protocols in a random
      order, 1 h apart. Physiologic variables at matched exercise stage I including
      heart rate (99 +/- 12 vs 101 +/- 14 bpm), rate-pressure product (15 +/- 3 vs 15
      +/- 3 bpm x mmHg x 10(3)), and VO2 (13.5 +/- 2.1 vs 13.0 +/- 3.0 ml.kg-1 x min-1)
      were not significantly different for exercise tests performed using the standard
      vs modified Bruce protocols respectively. Similarly, these parameters were also
      nearly identical at matched exercise stage II. However, peak VO2 was
      significantly higher using the standard vs modified Bruce protocol, although the
      difference was small. Therefore, these data indicate that a difference in the
      heart rate response at matched submaximal workrates on tests using these two
      protocols before and after a training program is most likely due to a training
      effect. Conversely, improvements in peak VO2 using the standard vs modified Bruce
      are at least in part due to inherent differences in responses between these two
      protocols.

PMID- 8133730
TI  - Evaluation of the Cosmed K2 portable telemetric oxygen uptake analyzer.
AB  - The purpose of this study was to determine the validity and evaluate the accuracy
      of a portable telemetric oxygen uptake analyzer (K2). Two experiments were
      carried out: a) using a mechanical lung, the accuracy of the K2 to measure oxygen
      fractions and minute ventilation following 10 and 60 min of warm-up was
      determined; and b) two maximal graded exercise tests (GXT) on 15 subjects, one
      with the K2 system and the other with a standardized breath-by-breath (BBB)
      system, while heart rate (HR), minute ventilation (VE), and oxygen uptake (VO2)
      were compared. Following 10-min warm-up prior to calibration, the K2
      underestimated the true oxygen fraction as early as 5 min into the test, and this
      value continued to decrease throughout the 30-min test. After 60 min of warm-up
      prior to calibration, the K2 accurately measured the true oxygen fraction for the
      first 15 min; at minute 20, and on to minute 30, the K2 underestimated the oxygen
      fraction. Ventilation volumes were not affected by warm-up time. Minute
      ventilation during the K2 GXT was significantly higher than VE for the BBB test.
      No significant differences were found between the HRs obtained with the BBB or K2
      systems. No differences in VO2 for any stage of the GXT were identified between
      the K2 device, BBB device or when a respiratory exchange ratio (RER) correction
      factor was applied to the K2 derived values. However, the RER correction factor
      did minimize the VO2 differences between the BBB and K2 systems. Therefore, we
      conclude that the K2 accurately measures VO2 during a GXT; however, its accuracy
      can be compromised by limitations inherent to the system.

PMID- 8133731
TI  - Target heart rates for the development of cardiorespiratory fitness.
AB  - The American College of Sports Medicine (ACSM) recommends the use of 40%, 60%,
      80%, and 85% of maximal oxygen consumption (VO2max) as target values in
      developing exercise prescriptions. Further, the ACSM states that 55%, 70%, 85%,
      and 90% of maximal heart rate (HRmax) may be used as indices of these respective
      levels of % VO2max for the general population. The current study evaluated this
      relationship between %HRmax and %VO2max in apparently healthy, young adults.
      Eighty-one men and 81 women between the ages of 18 and 34 engaged in an
      incremental exercise test to exhaustion. Linear regressions of %HRmax and %VO2max
      were performed on each subject. From these regressions, target values of %HRmax
      were computed for each individual. Mean percentages of HRmax were 63%, 76%, 89%,
      and 92% at 40%, 60%, 80%, and 85% of VO2max, respectively. At all of these values
      of %VO2max, the values obtained for %HRmax were significantly greater (P < 0.001)
      than those used by the ACSM. Fitness affected these results, particularly among
      men. High fit men averaged 2% higher in %HRmax than low fit men at any given
      value of %VO2max.

PMID- 8133732
TI  - Peliosis hepatis in a young adult bodybuilder.
AB  - Peliosis hepatis, an unusual condition characterized by blood-filled spaces
      within the hepatic parenchyma, usually occurs in a variety of chronic wasting
      diseases such as tuberculosis or malignancy. It has been described in patients
      undergoing therapy with anabolic steroids in pharmacologic doses over extended
      periods of time. To our knowledge it has not been described in athletes who
      utilize them for performance enhancement. This report concerns a 27-yr-old
      bodybuilder with peliosis hepatis, which developed after chronic intermittent use
      of anabolic steroids.

PMID- 8133733
TI  - Reporting behaviors and activity levels of intercollegiate athletes with an URI.
AB  - Some contend that upper respiratory illness (URI) causes more disability among
      athletes than all other diseases combined. The purpose of this study was to
      describe the reporting behaviors, activity levels, and perceived physical
      performance levels of intercollegiate athletes with an URI. Respondents rated the
      severity of 14 cold symptoms and indicated to whom they reported their cold, and
      within how many days. Additionally, respondents were to indicate whether they
      self-treated their illness, whether they missed a practice or game due to the
      cold, and whether the cold affected their performance. The subjects for this
      study were 290 intercollegiate athletes (165 males, 125 females) in a large
      Midwestern conference. The instrument was administered at three regular intervals
      during the sport seasons. There was a total of 118 illness episodes. Respondents
      reported their colds to the athletic trainer (50.4%, N = 61), doctor/nurse (33%,
      N = 41), and/or coach (28.3%, N = 32). Athletes reported their cold symptoms
      earliest to the coach (2.45 d) or athletic trainer (2.71 d). The number of days
      prior to reporting to a doctor or nurse was longer (3.64 d). Of the illness
      episodes reported, 17.8% (N = 21) caused the athlete to miss a practice and 5.1%
      (N = 6) caused the athlete to miss a game. Athletes with an URI felt in some
      instances that their illness episode affected their performance. Cold symptoms of
      cough, fever, laryngitis, aching muscles/joints, and nasal discharge were
      significantly (P < 0.05) correlated with reporting behaviors, activity levels,
      and/or perceived physical performance. Possible implications for athlete
      participation and education are offered.

PMID- 8133734
TI  - Introduction to respiratory control in skeletal muscle.
AB  - It is well known that a linear relationship exists for submaximum exercise
      intensity and oxygen consumption. Most of the increase in oxygen consumption is
      by skeletal muscle mitochondria for the purpose of producing enough ATP to match
      the energy needs of the muscle. The control of mitochondrial ATP production in
      muscle when workload is varied is a complex process and remains a very active
      area of research. Thus, the purpose of this symposium is to discuss the factors
      involved in the coupling between increases in work and increased oxygen
      consumption by muscle. The program will begin with a consideration of the
      challenges faced by skeletal muscle when attempting to meet its energy demands
      and the intracellular strategies that have evolved to optimize energy delivery.
      Next the major control theories for mitochondrial respiration will be discussed.
      Finally, experiments will be presented that are designed to determine which of
      these theories are best suited for specific skeletal muscle fiber types. It is
      hoped that the information presented will increase our awareness of different
      energy supply-demand strategies among fiber types and how supply-demand
      strategies are optimized by endurance training.

PMID- 8133735
TI  - The importance of the creatine kinase reaction: the concept of metabolic
      capacitance.
AB  - The creatine kinase reaction is traditionally viewed as providing an energy
      reserve in muscle. However, the physiological importance of this reaction (and
      the analogous invertebrate reaction catalyzed by arginine kinase) is better
      understood when viewed as providing metabolic capacitance. This capacitance
      allows reduction of peak rates of ATP synthesis in cells that alternate between
      periods of high and low energy consumption. Furthermore, the capacitance allows
      repayment of energy "debt" that is incurred during periods of high energy demand
      to occur during periods of low rates of energy consumption. The creatine kinase
      reaction provides facilitated diffusion of ATP and ADP, which leads to spatial
      buffering in addition to temporal buffering. Data are presented which suggest
      that the existence of the creatine kinase reaction allows muscle cells to
      maintain reduced mitochondrial volume, support larger diameter fibers, and
      express faster isoforms of myosin. These data lead to speculation that there may
      be a coupling in the expression of metabolic and contractile proteins.

PMID- 8133736
TI  - Factors affecting the rate and energetics of mitochondrial oxidative
      phosphorylation.
AB  - Mitochondrial oxidative phosphorylation in vivo is dependent on the degree of
      reduction of the intramitochondrial reducing power ([NADH]/[NAD+], cytoplasmic
      energy state ([ATP]/[ADP][Pi]) and intracellular oxygen pressure. Each parameter
      is independently regulated, and increased reducing power by activating the
      mitochondrial dehydrogenases allows higher energy state at a given rate of ATP
      synthesis or a higher rate of ATP synthesis at a given energy state. The
      mitochondrial respiratory rate is determined by demand, i.e., the rate of ATP
      utilization by the cell, while the cellular energy state at that demand level is
      determined by supply, i.e., activity of the dehydrogenases expressed as
      [NADH]/[NAD+] and of cytoplasmic oxygen pressure.

PMID- 8133737
TI  - Role of calcium in respiratory control.
AB  - Ca2+ ions activate four mitochondrial enzymes (viz. glycerol 3-phosphate
      dehydrogenase, pyruvate dehydrogenase phosphatase, NAD-isocitrate dehydrogenase
      and 2-oxoglutarate dehydrogenase) that are involved in substrate dehydrogenation
      and production of NADH as a substrate for oxidative phosphorylation. As cytosol
      Ca2+, and presumably mitochondrial Ca2+, concentrations are raised during muscle
      contraction, this is thought to provide a mechanism whereby the activity of
      oxidative phosphorylation is raised in working muscle without the necessity of
      unacceptably large decreases in adenine nucleotide phosphorylation potential.
      These ideas are explored in this article, with particular reference to the
      activation of pyruvate dehydrogenase in cardiac and skeletal muscle preparations
      and its dependence upon both cytosolic and intramitochondrial Ca2+ ion
      concentrations.

PMID- 8133738
TI  - Shoulder weakness in professional baseball pitchers.
AB  - The purposes of this study were to: 1) compare shoulder range of motion and
      strength in professional baseball pitchers (N = 47) compared with age-matched
      controls (N = 16), and 2) examine the relationship of injury history to strength
      and range of motion. Based on injury history pitchers were categorized as: 1)
      none (N = 26), 2) injury requiring conservative intervention (N = 9), or 3)
      injury requiring surgical intervention (N = 12). Range of motion was measured for
      internal rotation (IROM) and external rotation (EROM). Eccentric strength was
      measured by hand-held dynamometer for internal rotation (IR), external rotation
      (ER), abduction (ABD), and supraspinatus muscle (SUP) strength. Injury history
      had no effect on strength and range of motion. Dominant EROM was greater in
      pitchers, P < 0.0001, and controls, P < 0.05, with pitchers having greater EROM
      motion bilaterally, P < 0.0001. Pitchers were weaker in SUP on the dominant vs
      nondominant side, P < 0.0001, and on the dominant side for weight adjusted ER,
      ABD, P < 0.01, and SUP, P < 0.0001, compared with controls. In conclusion,
      dominance and pitching resulted in soft tissue adaptation. Pitchers displayed
      weakness in three of four tests by comparison with controls, suggesting that the
      demands of pitching are insufficient to produce eccentric strength gains and may
      in fact lead to weakness. Dominant-side SUP weakness in pitchers may reflect
      subclinical pathology or chronic fatigue.

PMID- 8133739
TI  - Testing models of respiratory control in skeletal muscle.
AB  - We examined the relationships between PCr and Pi vs oxygen consumption or twitch
      rate during stimulation of rat muscle in situ and of perfused cat biceps and
      soleus muscles. In fast-twitch muscles such as rat gastrocnemius and cat biceps,
      we found a linear relationship between PCr and oxygen consumption. This result
      favors thermodynamic regulation of oxygen consumption by cytoplasmic
      phosphorylation potential rather than kinetic regulation by ADP. PCr changes
      during stimulation of rat muscle depleted of total creatine or adenine nucleotide
      were also not consistent with simple kinetic regulation by ADP. In cat soleus
      (slow-twitch) muscle, the observation of nonexponential PCr changes during
      stimulation suggested more complicated regulation, possibly involving changes in
      mitochondrial redox potential.

PMID- 8133740
TI  - The influence of body mass in endurance bicycling.
AB  - Bicycling is a complex sport in which an athlete's energy cost is related to two
      principal forces: air resistance when traveling on flat terrain, and gravity when
      traveling uphill. Both wind tunnel data and physiological measurements suggest
      that air resistance scales as body mass to about the 1/3 power. Thus, large
      cyclists have only slightly greater frontal drags than small cyclists. If
      expressed relative to body mass, the frontal drag of small cyclists is
      considerably greater than that of large cyclists. The difference in frontal drag
      (energy cost) is not made up for by the advantage to small cyclists in relative
      VO2max (energy supply), since the mass exponent for drag (1/3) is closer to zero
      than that for VO2max (2/3). Thus, small cyclists should be at a disadvantage in
      flat time trials, which field data support. The energy cost of riding uphill
      slightly favors the large cyclist, because the weight of the bicycle represents a
      relatively smaller load than it does to a small cyclist. The mass exponent is
      0.79. Since this exponent is greater than that for VO2max, the small cyclists
      have an advantage in climbing, which is supported by field data.

PMID- 8133741
TI  - Mechanical energy management in cycling: source relations and energy expenditure.
AB  - Conservation of energy suggests that during cycling the constrained lower
      extremity is capable of delivering energy to the bicycle without expending energy
      to move the limbs. The purpose of this study was to characterize the management
      of mechanical energy during cycling and, specifically, to evaluate the potential
      for system energetic conservatism. Mechanical energy contributions derived from
      lower extremity energy sources were computed for 12 experienced male cyclists
      riding at five combinations of cadence and power output. The knee joint dominated
      (> 50%) in contributing to system energy and a moderate amount of energy was
      derived from hip joint reaction forces (> 6%). Energy generations and
      dissipations at the sources were sensitive to power output and, within the range
      of conditions studied, insensitive to cadence. Two energy models estimated
      mechanical energy expenditure under hypothetical single-joint and multijoint
      muscle operating conditions. When multijoint muscles were incorporated into the
      energy management analysis, a significant reduction in mechanical work relative
      to the single-joint muscle operation occurred. Energy savings associated with
      multijoint muscle energy transfers were enhanced at higher bicycle power levels,
      suggesting that conservation of mechanical energy is plausible given appropriate
      actions of two-joint muscles.

PMID- 8133742
TI  - Fluid ingestion during exercise in 25 degrees C water at the surface and 5.5 ATA.
AB  - To determine if drinking fluid altered exercise and thermal variables during 2-h
      immersions in 25 degrees C water, 11 male subjects were tested breathing air at 1
      ATA and HeO2 at 5.5 ATA (PO2 = 0.42 ATA). Each immersion consisted of four
      periods of 5-min rest, 5-min leg exercise at 50 W, and 20 min of exercise at 68
      +/- 3% VO2max. One test at each depth was done with no fluid (NF); one test was
      done with subjects consuming 125 ml of a 7% glucose polymer (GP) solution every
      30 min (total intake = 500 ml). Compared with NF, GP increased urine volume by
      469 +/- 118 and 443 +/- 82 ml at 1 and 5.5 ATA. Mean minute ventilation (VE) was
      reduced at depth by 10.1 +/- 0.6 and 5.1 +/- 0.6 l.min-1 for NF and GP,
      respectively (P < 0.05). GP trials reduced ventilatory equivalent (VEQ, VE/VO2)
      at 1 ATA, but increased it at 5.5 ATA, secondary to a small change in VE.
      Exercise heart rate was slightly lower at 5.5 ATA, but O2 pulse was the same
      among all conditions (17.2 +/- 0.1 ml O2.beat-1). Rectal temperature increased
      0.71 +/- 0.04 degrees C for all conditions. Total body heat flux and insulation
      were unaffected by fluid or hyperbaric treatments. These results indicate that
      drinking fluid during immersed exercise does not change fluid balance or thermal
      status at depths to 5.5 ATA. The modest changes in VEQ noted with fluid intake or
      hyperbaric exposure reflect inconsequential alterations in cardiopulmonary
      efficiency.

PMID- 8133743
TI  - Effect of dietary fat on metabolic adjustments to maximal VO2 and endurance in
      runners.
AB  - The present study examined the effects of dietary manipulations on six trained
      runners. The percent energy contributions from carbohydrate, fat, and protein
      were 61/24/14, 50/38/12, and 73/15/12 for the normal (N), fat (F), and
      carbohydrate (C) diets, respectively. Expiratory gases and blood responses to a
      maximum (VO2max) and a prolonged treadmill run were determined following 7 d on
      each diet. Free fatty acids (FFA), triglycerides, glycerol, glucose, and lactate
      were measured. Dietary assessment of subjects' N diet indicated that they were
      consuming approximately 700 kcal.d-1 less than estimated daily expenditures.
      Running time to exhaustion was greatest after the F diet (91.2 +/- 9.5 min, P <
      0.05) as compared with the C (75.8 +/- 7.6 min, P < 0.05) and N (69.3 +/- 7.2
      min, P < 0.05) diets. VO2max was also higher on the F diet (66.4 +/- 2.7 ml.kg-1
      x min-1, P < 0.05) as compared with the C (59.6 +/- 2.8 ml.kg-1 x min-1, P <
      0.05) and N (63.7 +/- 2.6 ml.kg-1 x min-1, P < 0.05) diets. Plasma FFA levels
      were higher (P < 0.05) and glycerol levels were lower (P < 0.05) during the F
      diet than during the C and N diets. Other biochemical measures did not differ
      significantly among diets. These data suggest that increased availability of FFA,
      consequent to the F diet, may provide for enhanced oxidative potential as
      evidenced by an increase in VO2max and running time. This implies that
      restriction of dietary fat may be detrimental to endurance performance.

PMID- 8133744
TI  - Comparison of cardiopulmonary responses to forward and backward walking and
      running.
AB  - Backward running has long been used in sports conditioning programs and has
      recently been incorporated into rehabilitative settings as a method of increasing
      quadriceps strength while decreasing the joint compressive forces about the knee.
      Although backward locomotion has been studied kinetically, the metabolic cost of
      backward walking and/or running has not to our knowledge been previously
      characterized. Oxygen consumption and other cardiopulmonary variables were
      measured under constant speed exercise during backward and forward walking at
      107.2 m.min-1 and during backward and forward running at 160.8 m.min-1. Peak
      oxygen consumption (VO2peak) was also measured during maximal incremental
      backward and forward running. VO2, HR, and blood lactate were significantly
      higher (P < 0.001) during backward walking and running than during forward
      walking and running. During backward walking and backward running, subjects
      exercised at 60% and 84% of their forward VO2peak, respectively. In conclusion,
      for a given speed, backward locomotion elicits a greater metabolic demand and
      cardiopulmonary response than forward locomotion. In general, these data suggest
      that while undergoing rehabilitation, an injured athlete may continue to exercise
      using backward walking/running at an intensity sufficient enough to maintain
      cardiovascular fitness levels.

PMID- 8133745
TI  - Validation of the Rockport Fitness Walking Test for adults with mental
      retardation.
AB  - This study determined if the generalized equations created for the Rockport
      Fitness Walking Test were a valid estimation of cardiorespiratory fitness for
      adults with mental retardation (MR). Subjects included 25 males and females (mean
      age = 33.3 +/- 7.4 yr) with MR. A maximal treadmill test was administered (mean
      VO2peak = 29.5 +/- 7.2 ml.kg-1 x min-1; 2.2 +/- 0.62 l.min-1). Subjects' age,
      weight, sex, walk time, and immediate post-HR were used in the generalized
      equations for predicting VO2peak (mean VO2peak = 36.5 +/- 7.6 ml.kg-1 x min-1 and
      2.7 +/- 0.66 l.min-1). Significant correlations (P < 0.01) were obtained between
      the measured and predicted peak VO2 levels. However, significant and consistent
      differences were also observed between the measured and predicted VO2peak values
      (P < 0.02). Only 28% (l.min-1) and 36% (ml.kg-1 x min-1) of the subjects'
      measured VO2peak fell within the prespecified value of the predicted VO2peak,
      thus indicating that the prediction equations overestimated the VO2peak and
      cardiovascular fitness levels of adults with MR.

PMID- 8133746
TI  - pH control in rat skeletal muscle during exercise, recovery from exercise, and
      acute respiratory acidosis.
AB  - We used 31P magnetic resonance spectroscopy to compare the response of rat
      skeletal muscle to three kinds of proton load. During exercise (tetanic sciatic
      nerve stimulation), protons from lactic acid were buffered passively and consumed
      by net hydrolysis of phosphocreatine (PCr). During recovery from exercise, the pH
      dependent efflux of protons produced by PCr resynthesis could be partially
      inhibited by amiloride or 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS),
      implicating both sodium/proton and bicarbonate/chloride exchange, but was not
      inhibited by simultaneous respiratory acidosis. In early recovery, up to 30% of
      proton efflux was mediated by lactate/proton cotransport. During acute
      respiratory acidosis at rest, the eventual change in muscle pH was consistent
      with passive buffering and was unaffected by amiloride or DIDS, implying no
      significant contribution of proton fluxes.

PMID- 8133747
TI  - Estimation of Bloch model MT spin system parameters from Z-spectral data.
AB  - Previous studies have described magnetization transfer (MT) Z-spectra in terms of
      a two-pool Bloch model, with six spin-system parameters KA, F, T1A, T1B, T2A, and
      T2B. By simulation, we show that a process including nonlinear constrained
      optimization can be used to accurately and uniquely estimate spin-system
      parameters from MT Z-spectra prepared by continuous wave (CW) RF irradiation.
      Experiments producing Z-spectra by pulsed RF irradiation give substantially
      different magnetization values, relative to MT acquisitions obtained by CW RF
      irradiation, at small offset frequencies, with a consequence that only T2B can be
      uniquely determined. However, several equalities and bounds involving four of the
      other parameters (KA, F, T1A, and T1B) are derived, which are applicable to
      pulsed data. These relationships allow calculation of "free pool" magnetization
      corresponding to complete saturation of the restricted pool, without requiring
      that this complete saturation be experimentally achieved. MT experimental data
      from pulsed RF irradiation on boiled egg albumin, obtained using a clinical whole
      body MRI system, are analyzed using an optimization algorithm and the derived
      expressions.

PMID- 8133748
TI  - Continuous measurement of cell volume changes in perfused rat salivary glands by
      proton NMR.
AB  - Changes in intracellular and extracellular water content have been measured in
      perfused rat salivary glands by repetitive application of an inversion recovery
      (IR) pulse sequence. The relaxation reagent Gd-DTPA (10 mM) was included in the
      perfusate so that the intracellular and extracellular water proton signals could
      be distinguished by their different longitudinal relaxation times. Changes in
      water content in response to altered perfusion pressure and perfusate osmolarity
      were determined at 30-s intervals and indicated a clear separation of the
      intracellular and extracellular components. Using a modification of the IR pulse
      sequence, changes in intracellular water content were also measured at 6-s
      intervals. With this time resolution, differences in the rates of cell shrinkage
      in response to hyperosmotic perfusates and the secretomotor agonist acetylcholine
      were observed. The results suggest that this approach offers a relatively
      noninvasive method for studying cell volume regulation in intact, perfused
      tissues and organs.

PMID- 8133749
TI  - In vivo and in vitro EPR oximetry with fusinite: a new coal-derived, particulate
      EPR probe.
AB  - The peak-to-peak line width (LW) of the first derivative electron spin resonance
      (EPR) spectrum of the coal maceral fusinite is reversibly broadened by O2. The
      extent of broadening per unit of partial pressure of oxygen (pO2) is unusually
      large, exceeding that of nitroxides by almost two orders of magnitude. This
      paramagnetic property of fusinite, combined with its very stable physicochemical
      properties and low toxicity, is shown to be of utility in the measurement of pO2
      in vitro and in vivo. Fusinite particles are endocytosed by chinese hamster ovary
      (CHO) cells in vitro; this is useful for intracellular O2 measurements with
      commercially available EPR spectrometers operating at 9.1-9.3 GHz. For
      measurement of oxygen in vivo using low frequency EPR (1.1-1.3 GHz), fusinite
      provides a sensitive and persistent means to measure pO2 in tissues. Particles
      implanted into the gastrocnemius muscle of A/J mice remained interstitially in
      the same position for months with undiminished sensitivity to pO2 and no specific
      toxic effects.

PMID- 8133750
TI  - Radioactive microsphere validation of a volume localized continuous saturation
      perfusion measurement.
AB  - Detre et al. (Magn. Reson. Med. 23, 37-45 (1992)) and Zhang et al., (Magn. Reson.
      Med. 25, 362 (1992)) have recently demonstrated a technique for the measurement
      of regional cerebral blood flow (rCBF) based on the continuous saturation (or
      inversion) of the arterial blood supply to the brain in rats at 4.7 T. In the
      work reported here, we combined this technique with volume localized (PRESS)
      readouts to benefit from recording "perfusion" signals averaged over a larger
      volume, resulting in rapid acquisition of data with sufficient signal-to-noise
      ratio for application at 2.0 T. In 10 baseline flow measurements, the mean error
      between the NMR technique and the microsphere flow measurement was -1.5% with a
      standard deviation of 15.2%. For five measurements obtained with occlusion of the
      middle cerebral artery, the mean error was -32.4 +/- 20.2%. Perfusion
      measurements from a single animal under hypercapnic conditions indicated that the
      NMR technique could underestimate rCBF at high flow rates. An error analysis of
      the NMR perfusion model is also presented, along with results for typical
      parameters encountered at 2.0 T.

PMID- 8133751
TI  - Water diffusion and acute stroke.
AB  - The occlusion of the middle cerebral artery was used as an experimental acute
      stroke model in 30 cats. The diffusion of water was followed by diffusion
      sensitized MRI between 1 and 15 h after induction of stroke. It is demonstrated
      that images representing the trace of the diffusion tensor provide a much more
      accurate delineation of affected area than images representing the diffusion in
      one direction only. The reason is that the strong contrast caused by the
      anisotropy and orientation of myelin fibers is completely removed in the trace of
      the diffusion tensor. The trace images show a small contrast between white and
      gray matter. The diffusion coefficient of white matter is decreased in acute
      stroke to approximately the same extent as gray matter. It is further shown that
      the average lifetime of water in extra and intracellular space is shorter than 20
      ms both for healthy and ischemic tissue indicating that myelin fibers are
      permeable to water. The anisotropy contrast did not change before or after
      induction of stroke, nor after sacrifice. Together, these observations are
      consistent with the view that the changes in water diffusion during acute stroke
      are directly related to cytotoxic oedema, i.e., to the change in relative volume
      of intra- and extracellular spaces. Changes in membrane permeability do not
      appear to contribute significantly to the changes in diffusion.

PMID- 8133752
TI  - Optimization of parameter values for complex pulse sequences by simulated
      annealing: application to 3D MP-RAGE imaging of the brain.
AB  - A number of pulse sequence techniques, including magnetization-prepared gradient
      echo (MP-GRE), segmented GRE, and hybrid RARE, employ a relatively large number
      of variable pulse sequence parameters and acquire the image data during a
      transient signal evolution. These sequences have recently been proposed and/or
      used for clinical applications in the brain, spine, liver, and coronary arteries.
      Thus, the need for a method of deriving optimal pulse sequence parameter values
      for this class of sequences now exists. Due to the complexity of these sequences,
      conventional optimization approaches, such as applying differential calculus to
      signal difference equations, are inadequate. We have developed a general
      framework for adapting the simulated annealing algorithm to pulse sequence
      parameter value optimization, and applied this framework to the specific case of
      optimizing the white matter-gray matter signal difference for a T1-weighted
      variable flip angle 3D MP-RAGE sequence. Using our algorithm, the values of 35
      sequence parameters, including the magnetization-preparation RF pulse flip angle
      and delay time, 32 flip angles in the variable flip angle gradient-echo
      acquisition sequence, and the magnetization recovery time, were derived.
      Optimized 3D MP-RAGE achieved up to a 130% increase in white matter-gray matter
      signal difference compared with optimized 3D RF-spoiled FLASH with the same total
      acquisition time. The simulated annealing approach was effective at deriving
      optimal parameter values for a specific 3D MP-RAGE imaging objective, and may be
      useful for other imaging objectives and sequences in this general class.

PMID- 8133753
TI  - Methods for reconstructing phase sensitive slice profiles in magnetic resonance
      imaging.
AB  - The experimental determination of slice profiles excited by applying
      radiofrequency pulses in the presence of a gradient generally results in
      magnitude profiles. The conditions necessary to obtain a phase-sensitive picture
      of the profile of a slice are discussed. A distinction is made between the
      "excitation profile" (distribution of the transverse magnetization immediately
      after the RF pulse) and the "slice profile" (distribution after refocusing by
      gradient reversal and/or imperfect gradient switching). Methods are presented
      that allow one to obtain either the excitation profile or the slice profile. It
      is shown that phase encoding along the direction of the slice selection gradient
      provides a convenient protocol for obtaining the distribution of both the real
      and imaginary parts of the slice profile. The phase sensitive excitation profile
      can be obtained by frequency encoding. These methods were used to evaluate the
      performance of various shaped pulses.

PMID- 8133754
TI  - MR imaging of flow through tortuous vessels: a numerical simulation.
AB  - A novel computer simulation technique is presented that allows the calculation of
      images from Magnetic Resonance Angiography (MRA) studies of blood flow in
      realistic curving and branching two-dimensional vessel geometries. Fluid dynamic
      calculations provide flow streamlines through curved or branching vessels. MR
      simulations generate images for specific MR pulse sequence parameters.
      Simulations of steady flow in carotid bifurcation and carotid siphon geometries
      as imaged by a standard, flow-compensated, spoiled gradient echo sequence
      illustrate the major features seen in clinical time of flight MRA studies. The
      simulations provide insight into a number of artifacts encountered in MRA such as
      displacement artifacts, signal pile-up, truncation artifacts, and intravoxel
      phase dispersion.

PMID- 8133755
TI  - MRA studies of arterial stenosis: improvements by diastolic acquisition.
AB  - Cardiac-phase-specific data acquisition is used to reduce signal loss in MR
      Angiography resulting from disturbed flow. RF pulses are delivered continuously
      throughout the cardiac cycle, but incrementation of phase-encoding gradients and
      data storage are enabled only during the chosen part of the cycle. Studies in a
      stenotic pulsatile flow phantom demonstrate that poststenotic signal loss is
      primarily determined by the mean flow velocity, and is not appreciably affected
      by acceleration or deceleration of the mean flow rate. The signal loss is least
      in diastole. In vivo studies in patients with carotid artery disease show that
      data acquisition in diastole reduces the apparent degree and extent of carotid
      bifurcation stenosis and provides a crisper definition of the vascular lumen. The
      additional time required for cardiac-phase-specific acquisition can be reduced by
      gating only the lower-order phase-encoding lines while retaining acceptable image
      quality.

PMID- 8133756
TI  - In vivo 19F spin relaxation and localized spectroscopy of fluoxetine in human
      brain.
AB  - Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug
      fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A
      quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a
      signal from the head 2 to 4 times stronger than for surface coils. It was used to
      measure the in vivo 19F spin-lattice relaxation time (T1) of fluoxetine for five
      patients by the inversion-recovery technique. The individual T1s varied from 149
      to 386 ms, which was attributed in part to interindividual differences based on
      the reproducibility of a phantom T1. The individual T1 correlated weakly with
      approximate brain concentration. A lower limit of 3 to 4 ms was found for the
      spin-spin relaxation time from line width measurements. Low resolution 4
      dimensional spectroscopic imaging confirmed that the single in vivo 19F resonance
      for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere
      (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for
      19 weeks was comparable with that seen for patients in vivo. The in vivo signal
      arose about equally from fluoxetine and the active metabolite norfluoxetine, as
      demonstrated by the in vitro 19F NMR spectrum of the lipophilic extract of a
      small section of brain. In vitro quantitation of frozen samples from three brain
      regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6
      micrograms/ml, which is higher than typically determined in vivo, and suggests
      that the fluorinated drugs may not be 100% visible in vivo.

PMID- 8133757
TI  - The presence of cytoplasmic lipid droplets is not sufficient to account for
      neutral lipid signals in the 1H MR spectra of neutrophils.
AB  - Stimulation of human peripheral blood neutrophils with lipopolysaccharide (LPS),
      arachidonic acid (AA) and oleic acid (OA) resulted in significant increases in
      cytoplasmic lipid droplets. This phenomenon was also observed in enucleated and
      degranulated cytoplasts prepared from neutrophils stimulated with LPS. In
      contrast, only LPS and high concentrations of OA (10 microM) produced an increase
      in the lipid intensities of the MR spectra of neutrophils as determined by COSY
      cross peak volume measurements. Lipid intensities in cells stimulated with OA
      (2.5 microM) and AA (2.5 microM) and phorbol myristate acetate (20 nM) were not
      elevated. LPS stimulation of resting cytoplasts resulted in increased lipid
      droplets but not MR lipid intensities. These data suggest that while cytoplasmic
      lipid droplets may correlate with MR lipid intensity under some circumstances,
      their presence is not sufficient to account for increased neutral lipid signals.

PMID- 8133758
TI  - A method for in vivo high resolution MRI of rat spinal cord injury.
AB  - We have developed an implanted radiofrequency coil to obtain high resolution in
      vivo MR images at 1.9 Tesla of rat spinal cords that have been injured using a
      standardized weight drop technique. The signal-to-noise ratio and motion artifact
      suppression of these images is superior to that achieved in earlier attempts at
      this field strength using an external surface coil. The high quality and spatial
      resolution provided by this technique afford the possibility for longitudinal
      studies of experimental spinal cord injury before and after treatment, as well as
      detailed correlation of in vivo MRI contrast, histopathological findings, and
      functional deficit, in a controlled setting.

PMID- 8133759
TI  - Discrimination of fluorinated uridine metabolites in N-417 small cell lung cancer
      cell extracts via 19F- and 31P-NMR.
AB  - 31P-NMR extract spectra of N-417 Small Cell Lung Cancer (SCLC) cells cultured
      with fluorouridine (FUrd) reveal new peaks with chemical shifts in the
      diphosphodiester and nucleoside triphosphate regions. These peaks were identified
      as FUTP, FUDP, FUDP-glucose, FUDP-glucuronate, FUDP-GlcNAc, and FUDP-GalNAc via
      enzymatic conversion and 19F- and 31P-NMR analysis. Distinct 19F chemical shifts
      were assigned for FUTP, FUDP, and the FUDP-sugars.

PMID- 8133761
TI  - Signal targeting with alternating radiofrequency (STAR) sequences: application to
      MR angiography.
AB  - We describe a time of flight subtraction method for cine MR angiography that
      provides nearly perfect suppression of background signal intensity with excellent
      flow contrast. The method consists of a preparation phase, during which the
      longitudinal magnetization of the target tissue is inverted on alternate
      acquisitions and the background tissue is presaturated, followed by a readout
      phase using a cine segmented turboFLASH sequence with a shared echo modification
      to improve temporal resolution. With appropriate alternation of the phases of the
      radiofrequency excitation pulses, there is cancellation of the background signal
      intensity but flow signal is optimized. By using a thick section (up to 25 mm),
      substantial portions of the vascular territory are encompassed in a single plane.
      This permits rapid, dynamic assessment of flow patterns in areas such as the
      circle of Willis, carotid bifurcation, or renal arteries. Applications of the
      method for bright and dark blood cine MR angiography are demonstrated.

PMID- 8133760
TI  - India ink: a potential clinically applicable EPR oximetry probe.
AB  - Using a material that already is in widespread use in humans, India ink, the
      first EPR measurements in a human have been made, using the India ink in a pre
      existing tattoo. The EPR spectra of India ink are very sensitive to the partial
      pressure of oxygen (pO2), thereby making it feasible to use this approach to
      measure pO2 in tissues in patients. This potentially provides a means to measure
      this parameter directly with a sensitivity, accuracy, and repeatability that have
      not been available previously, and thereby to be able to individualize and guide
      treatment of diseases such as cancer and peripheral vascular insufficiency.

PMID- 8133762
TI  - Simultaneous 31P NMR spectroscopy and EMG in exercising and recovering human
      skeletal muscle: technical aspects.
AB  - The bioenergetics of human skeletal muscle can be studied by 31P NMR spectroscopy
      (31P-MRS) and by surface electromyography (SEMG). Simultaneous 31P-MRS and SEMG
      permit accurate and noninvasive studies of the correlation between metabolic and
      electrical changes in exercising and recovering human skeletal muscle, a
      relationship that is still poorly understood. This study describes the
      optimization of skeletal muscle 31P-MRS in a whole-body magnet, involving surface
      coil design, utilization of adiabatic radio frequency pulses and advanced time
      domain fitting, to the technical design of SEMG. A nonmagnetic ergometer was used
      for ankle dorsiflexions that activated only the anterior tibial muscle as
      verified by post exercise imaging. The coil design and the adiabatic sech/tanh
      pulse improved sensitivity by 45% and 56% respectively, compared with standard
      techniques. Simultaneous electromyographic recordings did not deteriorate the NMR
      spectra. The VARPRO time domain fitting routine was very suitable for estimating
      31P muscle spectra. With these methods it was possible to accurately estimate
      parameters describing metabolic and electrical changes during rest, exercise and
      the entire recovery period with a 20-s time resolution on a standard 1.5 T whole
      body NMR scanner.

PMID- 8133763
TI  - Reconstruction of oropharyngeal defects utilizing a free radial forearm flap.
AB  - The authors report their experience with free radial forearm flaps for
      oropharyngeal reconstruction. Fifteen patients who submitted to intraoral
      reconstruction with this flap were followed for periods ranging from 3 to 36
      months, with a mean of 14 months. Ages ranged from 15 to 58 years with a mean of
      41. The defects were secondary to tumor ablation (11 patients), complications of
      conventional treatment for congenital deformities (3 patients) and trauma
      resulting from a gunshot wound to the upper lip and palate (1 patient). Total
      necrosis of 1 flap occurred and 1 patient required reoperation on the first
      postoperative day for revision of the anastomoses. Our results enable us to
      recommend the radial forearm flap as the flap of choice for reconstruction of
      extensive oropharyngeal defects.

PMID- 8133764
TI  - Replantation of digits: factors influencing survival and functional results.
AB  - Immediate survival and functional results were studied in 60 finger replants
      performed from 1980 to 1990. The follow-up ranged from 1 to 5 years with the mean
      of 2 years and 8 months. The survival rate achieved was 70% and was not related
      to the patient's age, the mechanism of injury, the level of amputation, the total
      ischemia time, the number of arteries and veins repaired or the type of vascular
      reconstruction. Sensory return was related to the mechanism of amputation and the
      total active motion was strongly correlated with the level of amputation. Of the
      16 digits that had only one artery anastomosed, there were 10 survivals (62.5%),
      and in 15 digits with anastomosis of two arteries, the success rate was 86.66% (P
      = 0.1244). The success rate in those cases in which vascular grafts were employed
      was 62.96% (P = 0.4161). In replantations with one, two or three veins
      anastomosed, the survival rate was 50%, 79.16% and 100%, respectively (P =
      0.1324).

PMID- 8133765
TI  - Vascularized fibular graft for management of severe osteomyelitis of the upper
      extremity.
AB  - The authors analyzed 14 patients with severe osteomyelitis of the upper extremity
      between 1985 and 1992, managed with the vascularized fibular graft. Eleven radii,
      two humeri and one ulna were reconstructed. Bone loss after resection ranged from
      6 to 12 cm (mean 8.14 cm). Follow-up ranged from 8 months to 7 years and 10
      months (mean 3 years and 3 months). The therapeutic applications of the
      vascularized fibular graft in severe bone infections of the upper extremity were
      discussed and the good results of this surgical procedure established it as a
      good option for treatment. Morbidity at the donor site was minimal.

PMID- 8133766
TI  - Extraplexual neurotization of brachial plexus.
AB  - The authors reviewed 62 neurotizations of the brachial plexus in 71 patients
      performed between 1974 and 1989. The nerves used were the accessory, the motor or
      sensory branches of the cervical plexus, and the intercostals. Twenty-five
      suprascapular nerves, 19 musculocutaneous, 4 medial roots of the median nerve,
      and 12 lateral roots of the median nerve were neurotized. The authors concluded
      that useful results can be achieved using extraplexual neurotizations.

PMID- 8133767
TI  - Treatment of congenital pseudarthrosis of the tibia by microsurgical fibula
      transfer.
AB  - Conventional methods for the treatment of congenital pseudarthrosis of the tibia
      (CPT) often lead to unsatisfactory results and so microsurgical fibula transfer
      (MFT) has appeared as an option to treat this challenging problem. In this series
      of 27 patients with CPT, we obtained satisfactory results in 23 as assessed by
      the timing of bone union and bone hypertrophy of the fibular transplant. The
      overall functional results were also good; in 18 patients, the residual
      shortening was less than 2 cm (with no limb shortening in 4) and in 7, shortening
      ranged between 2 and 4 cm. All 25 patients resumed normal walking without the
      help of braces after an average of 12 months. This report suggests that
      microvascular fibula transfers provide superior results in the treatment of CPT,
      especially when considering that many of such cases represented previous surgical
      failures.

PMID- 8133768
TI  - CO2 laser nerve welding: optimal laser parameters and the use of solders in
      vitro.
AB  - To improve the welding strength, an in vitro study was performed to investigate
      the bonding strength of CO2 laser nerve welding (LNW), with and without the use
      of human albumin solution, dried albumin solution, egg white, fibrinogen
      solution, fibrin glue, and red blood cells as a solder. Fifteen different
      combinations of laser power (50, 100, and 150 mW) and pulse duration (0.1 to 3 s)
      were used with a spot size of 320 microns. The results have been compared to
      suture, fibrin glue, and laser-assisted nerve repair (LANR). The strongest welds
      (associated with whitening and caramelization of tissue) were produced at 100 mW
      with pulses of 1.0 s and at 50 mW with pulses of 3 s. The use of a dried albumin
      solution as a solder at 100 mW with pulses of 1 s increased the bonding strength
      9-fold as compared to LNW (bonding strength 21.0 +/- 8.6 g and 2.4 +/- 0.9 g,
      respectively). However, positioning the nerves between cottons soaked in saline
      for 20 minutes resulted in a decrease of the bonding strength (9.8 +/- 4.5 g).
      The use of a 20% albumin solution and egg white, both at 50 mW with pulses of 3
      s, resulted in a bonding strength of, respectively, 5.7 +/- 2.1 g and 7.7 +/- 2.4
      g. Other solders did not increase the bonding strength in comparison to LNW. The
      substantial increase in bonding strength for some solders suggests that it is
      worthwhile to investigate the dehiscence rate and nerve regeneration of solder
      enhanced LNW in an in vivo study.

PMID- 8133769
TI  - Results of reconstruction of the facial nerve.
AB  - The results of surgical treatment for facial paralysis are still difficult to
      compare as there is no universal scoring method. The purpose of this
      communication is to review the results of reconstruction of the extratemporal
      facial nerve with nerve grafts using our own evaluation system. Fifty-nine
      patients were operated on during the period 1981-1991. They had lacerations or
      other trauma to the face which resulted in loss of continuity of the facial nerve
      or branches. Three groups were considered: (a) 12 patients had injuries involving
      the trunk and extending up to the main branches of the facial nerve; (b) 32
      patients had parotid laceration or contusion on the parotid area with resulting
      nerve defects extending from a main branch up to distal branches; and (c) 15
      patients had injuries on the distal branches: frontal, zygomatic, or mandibular.
      The sural nerve was used as the graft in all instances. The grafting procedure
      was performed from three weeks to six months after the trauma. The method of
      evaluation compares the normal with the paralyzed side. A score is given of 0 (no
      motion), 1 (weak motion), or 2 (strong motion), for each of six voluntary
      contractions: forehead, closure of eyelids and lips, traction, elevation, and
      depression of the lips. The assessment of involuntary mimic actions was done
      while observing blinking, speaking, smiling, and laughing. Mass movements were
      scored negatively. The numbers were recorded and the ratio between the paralyzed
      and normal side gave an estimate of the lack of symmetry.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8133770
TI  - Short communication: distal adrenergic innervation remains normal after
      perivascular sympathectomy.
AB  - Perivascular sympathectomy, which has been used for vasospastic disorders of the
      hands, was examined in experimental models. Perivascular sympathectomy was
      performed on the central ear vessels and forepaw metacarpal vessels of the rabbit
      and on the common digital vessels in the monkey. The effects on adrenergic nerves
      were studied using a glyoxylic acid-induced fluorescence method. Adrenergic
      nerves were removed only at the site of the perivascular sympathectomy and the
      distal adrenergic innervation appeared normal. Because the distal sympathetic
      nerves appeared normal after the operation, it should rather be called
      adventitectomy and we feel its clinical effects should be reevaluated.

PMID- 8133771
TI  - Experimental study of cryopreserved allogeneic transfer of vessel: preliminary
      report.
AB  - It has long been known that the antigenicity of tissues is depressed when they
      are kept at a very low temperature. In this study, Lewis rats and Brown Norway
      (B.N.) rats were used because these species are significantly dissimilar at the
      major histocompatibility complex (MHC) Femoral arteries were harvested from Lewis
      rats, frozen while lowering the temperature in a stepwise fashion to -70 degrees
      C. After three weeks of cryogenic storage, the arteries were transplanted into
      Lewis and B.N. rats. At various times from the first to the twelfth week after
      surgery, grafted vessels were observed, and pathological and electron microscopic
      studies were carried out. The vessels were found to be in good condition at the
      end of the 12 week observation period. These results strongly suggest that
      prolonged cryopreservation of vessels makes allotransplantation without
      immunosuppression possible.

PMID- 8133772
TI  - New and reproducible technique for experimentally induced middle cerebral artery
      stenosis.
AB  - A reproducible technique has been developed to create reversible middle cerebral
      artery (MCA) stenosis in the cat. Under pentobarbital anesthesia, the right eye
      was enucleated, MCA dissected and a suture looped around the vessel. A short
      segment of thicker suture was set horizontally on the MCA. The looped suture was
      then tied and the segment suture removed, resulting in partial stenosis. The knot
      could be easily removed, restoring blood flow. Perfusion and diffusion-sensitive
      magnetic resonance (MR) images were obtained over the next 6 hours to document
      cerebral blood flow abnormalities and developing ischemic changes, respectively.
      Laser-Doppler was performed to further document reduced flow through the
      ipsilateral hemisphere following MCA stenosis. Histopathologic sections were
      assessed for ischemic damage. Our results show this to be a reliable model of MCA
      stenosis and reperfusion, which is suitable for the evaluation of acute cerebral
      perfusion abnormalities resulting from arterial stenosis.

PMID- 8133773
TI  - Use of latissimus dorsi flap for reconstruction with prostheses after tumor
      resection.
AB  - Five latissimus dorsi musculocutaneous flaps (LD flap) were used for
      reconstruction with prostheses after resection of tumors between 1984 and 1991 in
      our hospital. Bony structures were reconstructed with prostheses and in three
      cases autoclaved autobone grafts were also needed. The prostheses and adjacent
      grafts were then wrapped by the LD flaps. Tumor sites included one humerus, two
      thighs, and two knees. All but one case healed primarily. The sole case of
      infection was successfully treated with debridement and irrigation. Due to the LD
      flaps' plentiful blood supply, we believe infection of the prosthetics can be
      avoided and good clinical results can be achieved using the flap with autoclaved
      autograft prosthetic composite reconstruction.

PMID- 8133774
TI  - Distal phalanx replantation.
AB  - Microsurgical replantation has been attempted in the distal phalanx of the
      digits. Twenty-three complete, single digit amputations are reviewed. The
      patients' ages ranged from 9 months to 48 years. Viability was 78%. Sensory
      recovery averaged 7 mm static two-point discrimination. Range of motion in the
      distal interphalangeal joint of the finger and the interphalangeal joint of the
      thumb averaged 64 and 51 degrees, respectively. Eight of the 17 successfully
      replanted digits had mild to moderate atrophy. Eighty-two percent of patients
      were able to use the replanted digit successfully in their daily work. We feel
      that distal digital replantation is rewarding. In successful cases, it always
      preserves acceptable function and good appearance at a price of an average of 2.3
      months off work.

PMID- 8133775
TI  - Free flap reconstruction of tumors involving the cranial base.
AB  - The authors describe their experience in treating 24 patients who underwent
      resection of tumors involving anterior, middle or posterior cranial fossa with
      immediate reconstruction. All were reconstructed with free flaps, 15 rectus
      abdominis, 4 radial forearm, 3 latissimus dorsi, 2 great omentum, and one
      scapular flap. There was one latissimus dorsi flap loss due to arterial
      thrombosis in a heavily irradiated patient. Three patients presented with a
      temporary cerebrospinal fluid leak, one of them with meningitis which resolved
      after intravenous antibiotics and continuous lumbar drainage. Fifteen patients
      were followed (mean 2 years). Five died of recurrence. Four presented local
      recurrence. Six patients are alive with no signs of recurrence. Free flaps,
      especially the rectus abdominis flap and the latissimus dorsi, are versatile
      flaps and may be easily positioned to cover several structures or anatomical
      surfaces.

PMID- 8133776
TI  - [XXXVIII Scientific Meeting of the Argentine Society of Clinical Investigation.
      Mar del Plata, 13-17 November 1993. Abstracts].

PMID- 8133777
TI  - Will all chemicals be carcinogenic to rodents when adequately evaluated?

PMID- 8133778
TI  - Detection of 6-thioguanine-resistant human peripheral blood lymphocytes using 5
      bromodeoxyuridine labeling in combination with immunocytochemical staining.
AB  - Measurement of frequencies of 6-thioguanine-resistant (TGr) human peripheral
      lymphocytes may contribute to quantitative genetic risk assessment in
      occupationally or environmentally exposed human populations. A simple procedure
      for the detection of TGr human peripheral blood lymphocytes was developed in our
      laboratory, using whole blood culturing and 5-bromodeoxyuridine (BrdU) labeling
      in combination with immunocytochemical staining. Modifications of the procedure
      designed to reduce the false positive effects of spontaneously cycling
      lymphocytes (phenocopies), and to optimize duration of BrdU labeling and the
      culturing period, were evaluated. A standard procedure was developed which
      applied 24 h cold storage of the diluted heparinized blood (1:10, v:v in RPMI
      1640 medium) at 4 degrees C to reduce the effect of spontaneously cycling
      lymphocytes, and whole blood culturing in RPMI 1640 complete medium with
      stimulation of T lymphocytes using phytohemagglutinin (PHA), selection of TGr
      lymphocytes by adding TG to a final concentration of 2 x 10(-4) M and, after 24 h
      of incubation, labeling of TGr lymphocytes with 2.5 x 10(-5) M BrdU during 16 h.
      Using this standard procedure, frequencies of TGr cells in 45 healthy individuals
      (aged 21-64) were observed to range from 0.3 to 229.8 x 10(-6), with a mean
      variant frequency (VF) (+/- SD) of 136 x 10(-6) (+/- 35.8). After exclusion of
      the one extremely high value of 229.8 x 10(-6), mean VF was 8.7 x 10(-6) (+/-
      14.1). A significant inverse correlation was found between logVF and the labeling
      index of control cultures (LIc), indicating that cultures with low LIc tend to
      yield higher VF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133779
TI  - Response of ataxia telangiectasia cells to restriction endonuclease induced DNA
      double-strand breaks: I. Cytogenetic characterization.
AB  - Ataxia telangiectasia (AT) and normal human lymphoblastoid cell lines have been
      treated with either X-rays or the restriction endonucleases PvuII and BamHI using
      streptolysin-O poration, and the frequencies of micronuclei or chromosomal
      aberrations measured. We report that AT cells (AT-PA) are hypersensitive to the
      restriction endonucleases PvuII and BamHI, inducing DNA double-strand breaks
      (dsb) with either blunt or cohesive termini, respectively. Our data indicates
      that AT-PA cells have a dsb processing defect that leads to a higher rate of
      conversion of dsb into chromosomal aberrations than in normal cells. AT-PA cells
      showed up to a 5-fold enhanced sensitivity to PvuII over the normal (N-SW) line,
      a result of an increase in frequencies of chromatid aberrations. Chromosome-type
      aberrations appeared not to be increased in AT-PA cells over those induced in the
      normal N-SW line. Particularly striking was the appearance in AT-PA of high
      frequencies of chromatid aberrations at the 24 h sampling time. BamHI also caused
      enhanced aberration frequencies in AT-PA cells although the cohesive-ended dsb
      caused by BamHI still appeared to be less effective in causing chromosomal
      aberrations than the blunt-ended dsb caused by PvuII in both AT-PA and N-SW, as
      we have previously reported for Chinese hamster cells. The enhanced effectiveness
      of cohesive-ended dsb in AT-PA cells over normal cells may be a result of altered
      processing of dsb by AT-PA cells or may be caused by conversion of some cohesive
      ended dsb into blunt-ended dsb by exonuclease digestion before ligation can take
      place.

PMID- 8133780
TI  - Cytogenetic biomonitoring in a Spanish group of agricultural workers exposed to
      pesticides.
AB  - Sister chromatid exchanges (SCE) and chromosome aberrations (CA) were studied in
      the lymphocytes of 70 male agricultural workers occupationally exposed to several
      pesticides and 69 matched controls, without indication of exposure to pesticides,
      from 'El Maresme' (Barcelona, Spain), Comparison between both groups revealed
      that the individuals exposed to pesticides show substantial clastogenic effects
      in their lymphocytes without indication of increases in the basal frequency of
      SCE; moreover, these effects seem to be additive, increasing with the duration of
      exposure measured in years. When two confounding factors such as age and smoking
      habits are considered, we found that these factors increase significantly the
      expression of SCE although no effect was detected in the expression of CA.

PMID- 8133781
TI  - Detection of whole chromosomes in micronuclei of cytokinesis-blocked human
      lymphocytes by antikinetochore staining and in situ hybridization.
AB  - The effect of cytochalasin B (Cyt-B; 3 and 6 micrograms/ml; for the last 28 h) on
      micronuclei (MN) was studied in 72-h purified lymphocyte cultures of three male
      donors. The frequency of MN was much higher in multinucleate cells (mean 100-204
      MN per 1000 cells) than in binucleate cells (mean 8.2-21.0 MN per 1000 cells),
      tetranucleate cells containing more MN than trinucleate cells. The presence of
      whole chromosomes in the MN was studied in two separate experiments by
      immunofluorescence using antikinetochore (CREST) serum and by a centromeric
      alphoid DNA oligomer probe (in situ hybridization, ISH). In the tri- and tetra
      nucleate cells produced by Cyt-B, MN were clearly more often kinetochore-positive
      (K+) (mean 82-86%) and centromere-positive (C+) (mean 73-83%) than in
      mononucleate cells of cultures containing no Cyt-B (mean 63% for CREST and 50%
      for ISH), indicating that most of the excess MN in the multinucleate cells were
      due to whole chromosomes. The binucleate lymphocytes had about as high prevalence
      of K+MN (mean 79-84%) as the tri- and tetra-nucleate cells, despite their low MN
      count. Also in the ISH analysis, the majority of MN in binucleate cells were
      positively stained (mean 58-62%). If it is assumed that the extra labelled MN are
      due to Cyt-B, the present findings suggest that Cyt-B could be responsible for
      approximately 45-57% (CREST data) or approximately 17-23% (ISH data) of MN in
      binucleate cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133782
TI  - Genetic differences between the standard Ames tester strains TA100 and TA98.
AB  - The standard Ames tester strains of Salmonella typhimurium are separated by many
      steps in their pedigree, some involving mutagen treatments, and contain
      independently isolated uvrB-bio-gal deletions and rfa mutations. In this work the
      araD531 mutation was introduced into the Ames tester strains TA100 and TA98. The
      responsiveness of the resulting strains (BA15 and BA14) to a number of chemical
      mutagens was then assessed by monitoring the induction of forward mutations to L
      arabinose resistance (Ara test). Here we have shown that these two strains of the
      Ames test differ greatly in their responses to mutagens, in ways that are not
      associated with the mutagenic specificities of the original his mutations. In
      general, the genetic background of strain TA100 appears to be more sensitive to
      the killing effects of chemicals than that of TA98. The greatest differences were
      found with nifurtimox (NFX) and its analogue, compound 1K. The Ara test responded
      to the mutagenic effects of these two nitrofurans when carried out in the genetic
      background of strain TA98 but not in that of TA100. A higher sensitivity to the
      lethal effects of NFX and 1K together with the greater nitro-reduction capability
      of strain TA100 as compared with TA98 might explain the differences. In
      conclusion, our results indicate that the standard Ames S. typhimurium tester
      strains are not isogenic and that genetic differences at loci other than his
      might be significant for mutagenicity testing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133783
TI  - Flow cytometric detection of micronuclei induced by chemicals in poly- and
      normochromatic erythrocytes of mouse peripheral blood.
AB  - In order to standardize automated scoring for the in vivo micronucleus (MN) test
      a flow cytometric method which recognized micronucleated polychromatic
      erythrocytes (MPCE) and micronucleated normochromatic erythrocytes (MNCE) in
      mouse peripheral blood developed by Grawe et al. (1992) has been modified and
      applied. Blood samples were purified with 35% percoll solution and stained with
      the RNA-specific dye thiazole orange (TO) and with the DNA-specific dye Hoechst
      33342 (HO) for dual laser flow cytometry. The TO fluorescent signals permitted
      the discrimination between polychromatic and normochromatic erythrocytes (PCE and
      NCE). Cytotoxic effects could be assessed by the reduction of PCE counts. The
      blue fluorescent signals of HO permitted the scoring of MN. The MPCE and MNCE
      were flow sorted for microscopic analysis and showed that 95% of the sorted cells
      actually contained MN. Three model chemicals, the clastogen mitomycin C, the
      aneugen colchicine and the industrial chemical acrylamide were tested at 24 h
      intervals after single intraperitoneal injection up to 72 h after treatment of
      male (102/ElxC3H/El)F1 mice. All three chemicals showed a dose-related maximum of
      the MPCE frequencies at 48 h while the MNCE frequencies stayed within the control
      range up to 72 h. The data obtained with the flow cytometric method were in good
      agreement with published results. The flow cytometric technique presented here is
      a fast, accurate and automated method for quantifying MPCE and MNCE in peripheral
      blood as an indicator of cytogenetic damage induced in the bone marrow and scored
      in peripheral blood samples. With minor modifications the technique will also be
      applicable to bone marrow samples.

PMID- 8133784
TI  - Strong intra-species variability in the metabolic conversion of six
      procarcinogens to somatic cell recombinagens in Drosophila.
AB  - Genetic heterogeneity in response to genotoxic carcinogens requiring metabolic
      conversion has been studied in Drosophila, using seven different genotypes in
      combination with the w/w+ eye mosaic assay for mitotic recombination. The set of
      tester strains examined consisted of four wild-type laboratory strains (Berlin-K,
      BK; Oregon-K, OK; Leiden-S, LS; and 91-C), and three DDT-resistant strains (91-R;
      Hikone-R, HR; and Haag-79, HG). Drosophila larvae heterozygous for the wild-type
      report gene w+ were exposed to benz[a]anthracene (BA), benzo[a]pyrene (BP), 9,10
      dimethyl-anthracene (DA), monocrotaline (MC), N-nitrosodimethylamine (DMN) or
      vinyl bromide (VBr). The primary conclusion regarding this study is the up to 60
      fold variation between different genotypes in mosaic spot frequencies induced by
      those procarcinogens and the non-existence of just one genotype to function as a
      'super-strain' in the activation of different classes of procarcinogens. By
      contrast, the seven Drosophila strains show a similar response to the direct
      acting agent methyl methanesulphonate. Among the six procarcinogens selected for
      this study, DMN and MC are readily detectable in all the distinct genotypes. Less
      satisfactory in terms of test performance are the either negative or weak test
      responses with BA in all four-wild type strains (LS, BK, OK and 91-C), and the
      weakly positive results for vinyl bromide in LS, BK and OK. The best overall test
      response was provided by strains HG and HR. It is concluded that the combined
      application of strains HG and HR safely and reliably should detect somatic cell
      recombinagens in the Drosophila w/w+ system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133785
TI  - Chromosomes lacking kinetochore proteins: their meta-anaphase location suggests
      potential malsegregation.
AB  - We have previously reported that a rare chromosome may not carry the kinetochore
      protein complex--the CENtromere Proteins or CENPs. These chromosomes should not
      bind to spindle microtubules and, hence, should be found peripheral to the meta
      anaphase arrangement exhibited by the chromosomes which do carry CENPs. This
      communication shows that this actually is the case. When 3T3 mouse cells were not
      treated with colcemid or hypotonic, the kinetochore-lacking (K-) as well as
      kinetochore-bearing (K+) chromosomes were found off the spindle zone. When the
      spindle is disrupted with mild hypotonic treatment or by colcemid, the frequency
      of K- chromosomes remains unchanged. However, even mild disruption of the spindle
      with hypotonic treatment increases the frequency of off-lying K+ chromosomes
      significantly. These data indicate that K- chromosomes do not bind to the spindle
      and, hence, are a factor in the genesis of aneuploidy. A considerable proportion
      of K- chromosomes carry the putative centromere DNA indicating that these are not
      acentric fragments. Since the CREST serum used recognizes all essential
      kinetochore proteins, the K- centromeres must also lack all essential CENPs.

PMID- 8133786
TI  - Analysis of micronuclei induced in mouse early spermatids by mitomycin C,
      vinblastine sulfate or etoposide using fluorescence in situ hybridization.
AB  - Non-radioactive in situ hybridization with mouse centromere specific (major)
      gamma satellite DNA probe was used to analyze the mechanism of induction of
      spermatid micronuclei (MN) caused by the alkylating agent mitomycin C (MMC), the
      spindle poison vinblastine sulfate (VBL) or the DNA topoisomerase II inhibitor
      etoposide (VP-16). Male mice were treated with a single i.p. injection of 25
      mg/kg VP-16, 5 mg/kg MMC or 2 mg/kg VBL, respectively. After 24 h (VP-16, VBL) or
      13 days (MMC) stage I spermatid slides were prepared and in situ hybridization
      was performed using a polymerase chain reaction amplified mouse (major) gamma
      satellite DNA probe. The observed MN frequencies for VP-16 and MMC, 6.2/1000 and
      7.5/1000 round spermatids, respectively, show a strong mutagenic effect on mouse
      germ cells compared with controls (1.4/1000 spermatids). VBL, on the contrary,
      induced a much lower total frequency of MN (2.8/1000 spermatids) compared with
      previous results on mouse somatic cells. Of MN in controls, 24% carried a FISH
      signal. After correcting for background, MMC induced 38.6% signal-positive MN,
      consistent with a predominantly clastogenic mode of action, while VBL induced
      67.9% signal-positive MN, consistent with a mainly aneugenic mechanism. VP-16
      induced 65.5% signal-positive MN, indicating that its MN-inducing capacity is
      mainly due to whole chromosome lagging.

PMID- 8133787
TI  - A comparison of micronucleus frequency and radiation survival in lymphoblastoid
      cell lines.
AB  - The relationship between the formation of micronuclei (MN) following the
      treatment of cell lines with ionizing radiation and the radiation survival of
      cell lines is important as the MN assay has the potential to predict radiation
      survival. Studies investigating the relationship have reached conflicting
      conclusions. We examined the relationship between MN formation and radiation
      survival measured by a clonogenic assay in six lymphoblastoid cell lines over a
      dose range of 0-2.0 Gy. We did not find a predictive relationship between the
      radiation induced MN frequency and the radiation survival in these cell lines.
      Possible reasons for the lack of correlation include variations in the percentage
      of scorable cells after irradiation and culture with cytochalasin B, different
      numbers of cells in the G1 phase of the cell cycle at the time of irradiation, a
      greater toleration of the loss of MN by hyperdiploid cell lines compared to
      diploid cell lines and quantitative differences in the conversion of chromosomal
      fragments into MN for the cell lines.

PMID- 8133788
TI  - Formaldehyde is a bacterial mutagen in a range of Salmonella and Escherichia
      indicator strains.
AB  - Formaldehyde was examined for bacterial mutagenicity using Escherichia coli
      WP2(pKM101) and WP2uvrA(pKM101), and Salmonella typhimurium TA1535, TA1537,
      TA1538, TA98, TA100 and TA102, in the absence of any exogenous source of
      metabolic activation. Using pre-incubation exposure, clear mutagenicity was seen
      for TA98, TA100 and TA102, and both E. coli strains. In standard plate
      incorporation assays, consistent mutagenicity was seen only for TA100 and
      WP2uvrA(pKM101). No evidence of mutagenicity was seen for TA1535, TA1537 or
      TA1538 using either method of exposure. These data confirm the enhanced ability
      of the pre-incubation method to detect the mutagenicity of formaldehyde both
      quantitatively, as expressed by numbers of revertant colonies, and qualitatively,
      in terms of the range of indicator strains reverted. The relatively greater
      sensitivity of the pre-incubation assay is probably due to better containment of
      a volatile agent and/or lack of interaction with agar during the initial period
      of exposure. The findings are consistent with the suggestion that formaldehyde
      induces lesions in bacteria which are, at least to some extent, excision
      repairable, and indicate that the presence of the R-factor plasmid may be
      required for the expression of its mutagenicity in excision repair-deficient
      Salmonella.

PMID- 8133789
TI  - Failure of N-acetylcysteine to protect the mouse bone marrow against the
      clastogenicity of 7,12-dimethylbenzanthracene.
AB  - De Flora et al. (1991a) have demonstrated a marked protective effect afforded by
      N-acetylcysteine (NAC) to the liver and lung of rats exposed to benzo[a]pyrene
      (BP) by intratracheal injection. Due to the protocol used by De Flora et al., BP
      was inactive in the bone marrow micronucleus assay and, consequently, the
      possible protective effect of NAC in this tissue could not be assessed. In the
      present study, three daily administrations of 7,12-dimethylbenzanthracene (DMBA;
      15 or 25 mg/kg/day via oral gavage) resulted in the expected increased in
      micronucleated polychromatic erythrocytes (MPE) in the bone marrow of male
      C57BL/6 mice 24 h after the final dose. Pretreatment of similar groups of mice
      with NAC (1 g/kg/day via oral gavage) 5 h before each administration of DMBA had
      no effect on MPE frequencies. It is concluded that NAC does not have a protective
      effect on the mouse bone marrow.

PMID- 8133790
TI  - Climacteric complaints and their relation to menopausal development--a
      retrospective analysis.
AB  - The present study had two objectives: (1) to register the prevalence of a number
      of climacteric complaints in a Danish general population cohort and (2)
      retrospectively to test the validity of an association between climacteric
      complaints, menopausal development, occurrence of life events and social
      background. A postal questionnaire sent to the 51-year-old female population
      living in four Copenhagen suburbs, (N = 597, response rate = 88%) included
      information on menstrual pattern and change, hormonal treatment, socioeconomic
      data and a 4-year retrospective annual registration of prevalence of a number of
      climacteric complaints and life events. Logistic regression analyses performed on
      a restricted sample (women who experienced a natural menopausal development)
      revealed prevalence of hot flushes, moodiness and fatigue to be significantly
      associated with transitions in menopausal status. Fatigue, moodiness and
      depression were strongly associated with socio-economic variables. Life events
      were only occasionally associated with prevalence of the studied complaints.

PMID- 8133791
TI  - Relations between anthropometric characteristics and degree of severity of the
      climacteric syndrome in Austrian women.
AB  - The connection between body-shape characteristics, namely distribution of
      subcutaneous fat, and the occurrence of psychic and somatic climacteric symptoms
      was investigated in 142 postmenopausal women from Eastern Austria. It was found
      that both psychic and somatic symptoms are significantly related to body-shape
      characteristics. With increasing breadth and circumference, i.e. a higher
      proportion of subcutaneous fat, the degree of severity of several symptoms
      increases, with the exception of hot flushes and sweating, dizziness, headache
      and palpitation. Since, in the climacteric, subcutaneous fat has a positive
      impact on the secretion of oestrogens and thus on climacteric symptoms, the
      results of the present study may be interpreted as an effect of the psychosocial
      stress to which corpulent women are exposed in our society because they do not
      fit the beauty ideal typical of our culture.

PMID- 8133792
TI  - Influence of spontaneous and surgical menopause on atherogenic metabolic risk.
AB  - We evaluated serum total-, LDL-, HDL-, cholesterol and triglycerides in 858
      women. Sixty-seven were in premenopause, 307 in perimenopause, 326 in spontaneous
      menopause, and 158 women underwent hysterectomy. Of these, 101 had bilateral
      ovariectomy, 24 with unilateral ovariectomy and 33 with retention of both
      ovaries. After correcting for chronological age and body mass index by variance
      analysis, it was found that total-, LDL- and HDL-cholesterol significantly
      increased during menopause without changes in the total cholesterol/HDL
      cholesterol, LDL-cholesterol/HDL-cholesterol and triglycerides/HDL-cholesterol
      ratio. The changes gradually occurred during the months preceding spontaneous
      cessation of menses. Atherogenic metabolic risk (as relative risk of high total
      and LDL-cholesterol, estimated by logistic regression analysis) significantly
      increased in all groups of women in reference to premenopause. The risk observed
      in surgical menopause with bilateral ovariectomy was higher than in spontaneous
      menopause, and conservation of ovaries in hysterectomized women seems to protect
      only partially against such an increase.

PMID- 8133793
TI  - Long-term effects of transdermal and oral estrogens on serum lipids and
      lipoproteins in postmenopausal women.
AB  - The transdermal and oral administration of estrogens for one year were compared
      with respect to the effects on lipid metabolism. Eighty-one postmenopausal women
      (1.5-3 years after menopause) were randomly divided into three groups. The first
      two groups received sequential estrogen treatment with either transdermal
      estradiol (Estraderm TTS, Ciba Geigy; 50 micrograms/day; 24 women) or 0.625
      mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both
      groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each
      cycle. Thirty-five subjects served as control group without therapy. No
      significant changes in the lipid profile was observed in control subjects after 1
      year of follow-up. Serum triglycerides decreased significantly (-10.9 +/- 26%
      S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral
      estrogen group. Comparable significant decreases in total and low density
      lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on
      estrogen replacement therapy. High density lipoprotein (HDL) cholesterol
      significantly diminished in transdermal estradiol group, but it rose slightly in
      the oral estrogen group. Thus the fraction of HDL cholesterol over LDL
      cholesterol did not change in the transdermal group whereas it significantly rose
      in subjects treated with oral estrogens. It remains to be established to what
      extent these differences on lipid metabolism are relevant for the prevention of
      cardiovascular diseases.

PMID- 8133794
TI  - Gynecologic complications of cyclic estrogen progestin therapy.
AB  - We evaluated the long-term gynecologic risks of postmenopausal estrogen therapy
      in conjunction with cyclic, monthly progestin (progestin-estrogen replacement
      therapy, or PERT). Our medical record review showed that incidence of abnormal
      vaginal bleeding necessitating gynecologic procedures for evaluation was
      significantly higher (RR, 3.1; 95% CI, 2.1-4.5), as was the rate of endometrial
      biopsy (RR, 3.4; 95% CI, 2.3-5.1), among women receiving PERT than among women
      not receiving hormone therapy. We also identified a non-significant trend toward
      a higher rate of dilation and curettage (RR, 1.5; CI, 0.7-3.3) among women
      receiving PERT. However, rates of endometrial hyperplasia and hysterectomy were
      similarly low in both groups. PERT apparently protects women against these
      serious gynecologic consequences previously seen in women taking unopposed
      estrogen.

PMID- 8133795
TI  - Decrease of bone mineral density during estrogen substitution therapy.
AB  - A decrease in bone mineral density (BMD) in patients treated with hormone
      replacement therapy (HRT) is sometimes observed in clinical practice. In order to
      assess the frequency and the characteristics of these cases, we reviewed the data
      of 102 women treated with HRT for more than 2 years, and who had undergone at
      least 3 lumbar BMD measurements during that period. For each patient, a linear
      function was fitted to the BMD data in relation to time. The slope was
      calculated. There was an overall gain in BMD during treatment, mean (+/- S.E.M.)
      values of slope 0.007 g/cm2/year (+/- 0.002). Fifty-three patients had a slope
      higher than 0.005, 28 a slope close to 0 (between 0.005 and -0.005) and 21 a
      slope lower than -0.005. By dividing the patients in tertiles of slopes (tertile
      I: slope < 0; tertile II: 0 < slope < 0.011; tertile III: slope > 0.011),
      significant differences were observed between the three groups of slope for the
      initial BMD (P < 0.001), hydroxyproline/creatinine ratio (P < 0.01), weight,
      DHEAS and alkaline phosphatase (P < 0.05). Only 1 of the 15 patients with a low
      bone mass (lower than mean +/- 1 S.D.) had a negative slope, while 9 of the 16
      with a high-bone mass (higher than mean +/- 1 S.D.), had a negative slope. Under
      HRT, about 21% of postmenopausal women have a slight decrease in BMD as assessed
      by DPA. Because of the DPA coefficient of variation, however, the exact number of
      bone losers cannot be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133796
TI  - Effects of nandrolone decanoate on bone mass in established osteoporosis.
AB  - A double-blind, randomized, placebo-controlled study was conducted in 46
      postmenopausal women with established osteoporosis in order to assess the long
      term effects of nandrolone decanoate on the bone mineral density (BMD) of the
      lumbar vertebrae and of the distal third of the radius and on the biochemical
      markers of bone turnover. The patients received intramuscular injections of
      placebo or 50 mg nandrolone decanoate every 3 weeks for 18 months. Thirty-two of
      the initial 46 patients completed 1 year of study and 25 completed the whole
      study period of 18 months. Overall, vertebral BMD increased by 2.9% in the
      nandrolone decanoate group and fell by 2.3% in the placebo group. Radial BMD
      showed a slight but transient improvement, with a subsequent return to basal
      levels in the nandrolone decanoate group, whereas there was a progressive
      decrease in the placebo group. Patients treated with nandrolone decanoate also
      complained less of bone pain. Urinary hydroxyproline decreased significantly in
      treated patients, whereas osteocalcin tended to increase, but the change was not
      significant. HDL cholesterol concentrations decreased only slightly and
      haemoglobin increased significantly in the nandrolone decanoate group. Two
      patients treated with nandrolone decanoate withdrew from the study because of
      hirsutism and hoarseness. The results indicate that nandrolone decanoate exerts
      positive effects on vertebral BMD and on bone pain in patients with established
      postmenopausal osteoporosis.

PMID- 8133797
TI  - Thymocyte apoptosis.

PMID- 8133798
TI  - Serological reactivity of sera from scrub typhus patients against Weil-Felix test
      antigens.
AB  - Sera from 17 patients of scrub typhus in the acute and convalescent phases were
      tested by indirect immunoperoxidase test, Weil-Felix (WF) test, enzyme-linked
      immunosorbent assay (ELISA), and immunoblotting. In the comparison of antibody
      titers between acute- and convalescent-phase sera, we recognized a parallelism of
      increment between the titers in WF test and titers of immunoglobulin M (IgM) in
      ELISA against Proteus mirabilis strain OXK-whole cells and OXK
      lipopolysaccharides (Proteus OXK-LPS). Furthermore, IgM antibodies from almost
      all of WF test-positive sera recognized LPS from Proteus OXK in immunoblotting.
      Based on these results, it was concluded that IgM antibody rather than IgG may
      participate in WF test, and that Proteus OXK-LPS may have one of antigenic
      epitopes common to the components of R. tsutsugamushi.

PMID- 8133799
TI  - Quantitative analysis of polymyxin B released from polymyxin B-treated dormant
      spores of Bacillus subtilis and relationship between its permeability and
      inhibitory effect on outgrowth.
AB  - Polymyxin B, one of the cyclic polypeptide antibiotics, binds to the coat of
      Bacillus subtilis dormant spores and inhibits them from growing after
      germination. When about 2.8 x 10(8) cells/ml of polymyxin B-treated dormant
      spores were incubated in heart infusion broth, 3.6 micrograms/ml of polymyxin B
      were released into the liquid medium during germination. Incubation of the same
      concentration of polymyxin B-treated ones in 100 mM CaCl2 solution released 4.0
      micrograms/ml of the antibiotic. The effect of various concentrations of
      polymyxin B on germination, outgrowth and vegetative growth of the dormant spores
      was investigated; the results showed that concentrations of 4.0 micrograms/ml and
      higher of the antibiotic inhibited their outgrowth and vegetative growth after
      germination. Young vegetative cells were less sensitive to the antibiotic than
      germinated spores. In addition to these results, immunoelectron microscopy with
      colloidal gold particles indicated that polymyxin B permeated into the core of
      the germinated spores and inhibited them from outgrowing.

PMID- 8133800
TI  - Immunological properties of TtT/M-87 cell line established from murine pituitary
      tumor-associated macrophages.
AB  - TtT/M-87 cell is a macrophage cell line established from thyrotropic pituitary
      tumor tissues in mouse. In this paper, we report the immunological properties of
      M-87 cells as a model of tumor-associated macrophage. Contrasting with resident
      peritoneal macrophages, M-87 cells constitutively secreted small but significant
      amounts of TNF-alpha and IL-1 alpha, which were detectable in both biological
      assays (cytotoxic activity for L929 and co-mitogenic activity for Con A-induced T
      cell proliferation, respectively) and ELISA, and produced larger amounts of these
      cytokines upon stimulation with LPS. They expressed MHC class II molecules on
      their cell surface without stimulation by IFN-gamma. The accessory or antigen
      presenting cell activity in antibody-producing response of spleen lymphocytes to
      sheep red blood cells was shown to be much higher in M-87 cells than normal
      peritoneal macrophages. In addition, when normal spleen lymphocytes were cultured
      with allogeneic tumor cells, such as EL-4 and S-180, in the presence of M-87
      cells, lymphocytes reactive to stimulator cells were activated to manifest
      inhibitory effect on the tumor cell growth and also to manifest specific
      cytotoxic effect on the allogeneic tumor cells. These results show that M-87
      cells derived from tumor-associated tissue are activated macrophages and that
      they are inhibitory to tumor cell growth and augmentative in the induction of T
      cell-mediated immune responses.

PMID- 8133801
TI  - Characterization of cell growth-inhibitory factor in inflammatory peritoneal
      exudate cells of rats.
AB  - We characterized the nature and reaction mode of the cell growth-inhibitory
      factor (here designated CGIF) from rat peritoneal exudate cells (PEC). The
      soluble fraction separated from the lysate of Enterococcus faecalis-induced 24 hr
      PEC completely inhibited Con A-induced thymocyte mitogenesis. Gel filtration
      chromatography showed that CGIF has a molecular weight of approximately 23-25
      kDa. Isoelectric focusing with Rotofor indicates that the factor has an
      isoelectronic point of 5.8-6.4. CGIF was inactivated by treatment at 70 C, for 30
      min or by tryptic digestion, but the activity was not destroyed by the reduction
      with dithiothreitol. As well as thymocyte proliferation, CGIF completely
      suppressed 3H-thymidine incorporation of splenocytes which were stimulated by
      either Con A or LPS, suggesting the factor is effective on both T and B cells.
      The acting point of the inhibitor appeared to be a later stage of the lymphocyte
      activation sequence, since it was still effective when added 28.5 hr after the
      addition of Con A. CGIF also reduced the viability of these cells when added with
      mitogens such as Con A or LPS. CGIF thus appears to be distinct from interleukin
      1 receptor antagonist or transforming growth factor-beta.

PMID- 8133802
TI  - Characterization of Vibrio cholerae O139 synonym Bengal isolated from patients
      with cholera-like disease in Bangladesh.
AB  - Vibrio cholerae O139 (synonym Bengal), a novel serovar of V. cholerae, is the
      causative agent of large outbreaks of cholera-like illness currently sweeping
      India and Bangladesh. Eight randomly selected V. cholerae O139 isolates were
      studied for their biological properties, which were compared with those of V.
      cholerae O1 and other V. cholerae non-O1. The V. cholerae O139 isolates were
      characterized by the production of large amount of cholera toxin,
      hemagglutination, weak hemolytic properties, resistance to polymyxin B, lysogeny
      with, and production of, kappa type phage (4/8 isolates only), and resistance to
      both classical and El Tor-specific phages. Thus, V. cholerae O139 isolates had an
      overall similarity with V. cholerae O1 El Tor.

PMID- 8133803
TI  - Simple purification method for a Vibrio vulnificus hemolysin by a hydrophobic
      column chromatography in the presence of a detergent.
AB  - A Vibrio vulnificus hemolysin (VVH) was purified by two steps of hydrophobic
      column chromatography on Phenyl-Sepharose HP. The first chromatography was
      carried out at pH 6.0. In this pH condition, VVH efficiently bound to the column,
      but the hemolysin fraction eluted was accompanied with colored substance(s). To
      eliminate this colored substance, the second chromatography was carried out at pH
      9.8 in the presence of 1% 3-[(3-cholamidopropyl) dimethylammonio]-1
      propanesulfonate (CHAPS), a zwitterionic detergent. Homogeneity of the hemolysin
      thus obtained was shown by polyacrylamide gel electrophoresis. The specific
      activity increased 33,600 times and the yield was 35%. The method is simple and
      useful to supply enough VVH for study of the role of the hemolysin in the
      infection by V. vulnificus or on the mechanism of action of the hemolysin.

PMID- 8133804
TI  - Effect of heparin on hemagglutinin of herpes simplex virus type 1.
AB  - Heparin inhibited the hemagglutinin activity of herpes simplex virus (HSV) type
      1. The minimal inhibitory concentration of heparin required to inhibit 8
      hemagglutination (HA) U of HSV ranged from 0.005 to 0.01 U/ml. Mouse erythrocytes
      failed to combine with the HA inhibitory factor of heparin. On the other hand,
      mouse erythrocytes treated with heparinase had greatly reduced agglutinability by
      HSV. Virus-heparin complex formation was observed by sedimenting heparin with the
      virus particles.

PMID- 8133805
TI  - Dual infection of HIV-1 and HTLV-I in south India: a study on a patient with AIDS
      related complex.
AB  - A dually HIV- and HTLV-infected ARC patient was found by serological studies in
      South India. These viruses were isolated and molecular study showed that the
      patient had both HIV-1 and HTLV-I but not HIV-2 and HTLV-II. In addition to this,
      9 other dually infected persons which include another full-blown AIDS case have
      been identified as on July 1993 in South India. Our findings provide an
      opportunity to clarify geographical distribution of these human retroviruses.

PMID- 8133806
TI  - Diagnosis of genital herpes by polymerase chain reaction amplification.
AB  - A new polymerase chain reaction (PCR) method employing type-specific primers and
      probes was applied to 114 clinical specimens obtained from 58 female patients
      with genital lesions or who had a history of genital herpes. Ten and 15
      specimens, respectively, were positive for herpes simplex virus (HSV)-1 and HSV-2
      by cell culture. All of 10 culture-confirmed HSV-1 cases and 11 of 15 (73%)
      culture-confirmed HSV-2 cases were identified by PCR. Although there were several
      cases with discrepancy between cell culture and PCR for HSV-2, the results
      suggest that this PCR procedure could be applied to clinical specimens from the
      female genital tract.

PMID- 8133807
TI  - Small, round-structured viruses (SRSVs) associated with acute gastroenteritis
      outbreaks in Gifu, Japan.
AB  - Two outbreaks of non-bacterial gastroenteritis occurred in Gifu prefecture in
      January 1989 and in January 1991. Both outbreaks were closely related to the
      consumption of raw oysters, and showed similar clinical features. Small, round
      structured virus particles were found in patient stools in both outbreaks by
      electron microscopy. The role of these particles as the causative agents of the
      outbreaks were strongly suggested by immune electron microscopy and/or western
      blotting immunoassay. When compared with SRSV-9 (Tokyo/SRSV/86-510) reported
      previously (Hayashi et al, J. Clin. Microbiol., 27: 1728-1733, 1989), it was
      found that these viral particles were antigenically similar to SRSV-9, and had a
      major structural protein of 63 kilodaltons (kDa). Further, the prevalence of this
      agent in Gifu area was examined by western blot antibody assay using 67 serum
      samples collected from the inhabitants in 1991. The results indicated the
      circulation of the same or antigenically similar agent in this area.

PMID- 8133809
TI  - Lorenzo's oil: a reassessment.

PMID- 8133810
TI  - We can get rid of scabies: new treatment available soon.

PMID- 8133811
TI  - The use of alternative therapies by children with cancer.
AB  - OBJECTIVE: To identify the nature and prevalence of therapies used by children
      with cancer as alternatives to orthodox medical treatment. DESIGN: A descriptive
      study in which the parents of children with cancer completed a questionnaire
      describing the use of alternative therapies by their children. SUBJECTS: Children
      diagnosed with cancer, excluding brain tumours, at the Women's and Children's
      Hospital, South Australia, from July 1988 to July 1992. RESULTS: Approximately
      46% of the children with cancer had used at least one alternative therapy. In
      general, parents reported that the therapies were used as an addition to orthodox
      medical treatment rather than as an alternative. Less than 50% of the parents had
      discussed the use of the alternative therapies with the children's doctors.
      CONCLUSIONS: A substantial proportion of children with cancer use alternative
      therapies and the use of these therapies is often not discussed with the
      children's medical practitioners. There is a continuing need to consider how to
      better provide, within the context of orthodox medical treatment, those elements
      of their children's care which parents currently seek from alternative therapies.

PMID- 8133812
TI  - On eye of newt and bone of shark. The dangers of promoting alternative cancer
      treatments.

PMID- 8133813
TI  - Improving communication with parents of children with cancer.

PMID- 8133814
TI  - Progress in childhood cancer: can it be maintained?

PMID- 8133815
TI  - Cardiac surgery in the very elderly.
AB  - OBJECTIVE: To determine the results of cardiac surgery in the very elderly.
      DESIGN AND SUBJECTS: A retrospective study of 56 very elderly patients (mean age
      82 years, range 79-89 years) undergoing open heart surgery between 1988 and 1991.
      Thirty-three patients had coronary artery bypass grafting, 12 had valve
      replacement alone and 11 had valve replacement with an associated procedure.
      SETTING: St Francis Xavier Cabrini Hospital, Melbourne--a large private hospital.
      RESULTS: There were four in-hospital deaths (7%). The one-year actuarial survival
      rate was 88%. Of the 49 survivors, 92% were in New York Heart Association (NYHA)
      Class III or IV before operation, whereas 96% were in NYHA Class I or II a mean
      of 15 months after operation. CONCLUSION: In very elderly patients with medically
      refractory cardiac symptoms, cardiac surgery has a tolerable mortality and
      provides excellent relief of symptoms.

PMID- 8133816
TI  - Stroller safety.
AB  - OBJECTIVE: To assess the incidence and type of stroller injuries in South
      Australia and factors contributing to their occurrence. DESIGN: Retrospective
      review of South Australian Health Commission Injury Surveillance data for
      Adelaide Children's Hospital, Modbury Hospital and Queen Elizabeth Hospital (1986
      1992); a prospective survey of 150 stroller users in three metropolitan shopping
      malls; and testing of backward tipping using loads determined by the AS/NZS 2088
      standard. RESULTS: One hundred and forty-nine attendances for unintentional
      injury resulted from infants either falling out of strollers and prams, or from
      entrapment of digits in strollers. Eleven infants (7.4%) required admission. One
      hundred and five injuries (70%) occurred between nine and 15 months of age.
      Eighty-nine (60%) involved either head/facial/dental injuries or concussion. The
      survey showed that only 14 strollers (9%) were used correctly (children
      appropriately harnessed and no shopping on the handles). Five strollers tipped
      over while carrying an 8 kg load when a 5 kg weighted shopping bag was placed on
      their handles. One stroller tipped over when a weight of 2 kg was applied at the
      handle on a 12 degree ramp with an 8 kg load. Only 11 of the 23 strollers
      commercially available in Adelaide in October 1992 carried the non-mandatory
      stroller standard. CONCLUSION: Stroller accidents are a common source of injury
      and usually result from incorrect use. The stroller standard should be made
      mandatory and revised to include a shoulder harness, lower the centre of gravity
      and provide shopping storage.

PMID- 8133817
TI  - Traffic and noise in children's wards.
AB  - OBJECTIVE: To measure pedestrian traffic volumes and noise levels in paediatric
      open bay areas and discuss their impact on the care of sick children. METHODS:
      Between August and October 1992, we recorded the number and duration of entrances
      to two open bay areas comprising eight and ten beds respectively in a ward for
      infants and a ward for older children. Eight 24-hour periods (1200 to 1200)
      Friday to Saturday were assessed. Noise levels in decibels dB(A) were measured at
      15-minute intervals. RESULTS: In an average 24-hour period, 5.5 (SD +/- 1.3)
      patients in the infants' ward and 9.5 (SD +/- 0.6) patients in the children's
      ward received 617 (SD +/- 85) and 683 (SD +/- 64) visits by 104 (SD +/- 20) and
      110 (SD +/- 2) individuals respectively. The maximum numbers of visits per hour
      were 57 (SD +/- 14) and 54 (SD +/- 8) visits between 1500 and 1600 hours on
      Friday for each ward. Visits tended to be brief; 225 (SD +/- 23) and 217 (SD +/-
      34) visits were of less than one minute's duration. The maximum noise levels of
      57.3 dB(A) (SD +/- 6.3) and 64.6 dB(A) (SD +/- 3.5) occurred at 1000 Saturday and
      1900 Friday and coincided with peak traffic volumes. CONCLUSIONS: Open bay areas
      generate high traffic volumes and coincident noise. Consideration should be given
      to either modifying or abolishing open bay areas and to general noise control
      measures.

PMID- 8133818
TI  - Bicycle incidents in children--abdominal trauma and handlebars.
AB  - OBJECTIVES: To investigate the frequency and causes of bicycle related abdominal
      injuries in children and to examine the pattern of presentation. DESIGN: The
      study was a prospective study of bicycle related injury in children less than 15
      years of age presenting to two paediatric hospitals (15 April-30 June 1992) and
      three general hospitals (1 August 1991-30 June 1992). RESULTS: In a series of 813
      children, 41 sustained non-penetrating abdominal trauma due to a bicycle
      incident. In 21 cases, handlebar trauma was responsible. Ten of these children
      suffered life-threatening intra-abdominal injury. Handlebars with no plastic or
      foam covering of the metal ends were involved in all ten cases. In several of
      these cases, presentation to hospital was delayed and in others confirmation of
      the extent of injury took up to 48 hours. The length of hospital stay for those
      with significant intra-abdominal organ damage ranged from two to 156 days.
      CONCLUSIONS: Intra-abdominal trauma must be considered when dealing with children
      who are victims of bicycle trauma. Impact with handlebars may have occurred and
      some form of padded protection of handlebar ends is recommended unless their
      design can be suitably modified.

PMID- 8133819
TI  - Phosphate enema poisoning in children.
AB  - OBJECTIVE: To report a case of hypocalcaemic tetany occurring in a child
      secondary to two phosphate enemas administered for faecal retention, and review
      the literature of phosphate enema toxicity in children. CLINICAL FEATURES: A 23
      month-old child with a repaired anorectal malformation and associated unilateral
      renal hypodysplasia presented with hypocalcaemic tetany (minimum serum calcium
      level, 1.11 mmol/L), hyperphosphataemia (maximum serum phosphate level, 6.06
      mmol/L), hypokalaemia (minimum serum potassium level, 1.9 mmol/L) and dehydration
      10 hours after the administration of two phosphate enemas for acute on chronic
      faecal retention. MANAGEMENT AND OUTCOME: Management consisted of parenteral
      rehydration, potassium supplementation, calcium gluconate, an enterally
      administered phosphate binder and saline bowel washouts to evacuate the remaining
      enema. She was discharged on day eight, with normal biochemical parameters and no
      neurological sequelae. CONCLUSION: The use of phosphate enemas in children under
      five years of age is associated with significant morbidity due to
      hyperphosphataemia, hypocalcaemia, hypokalaemia and dehydration. They should not
      be used in children under two years of age, and should be used only with extreme
      caution in children aged two to five years, especially in those with underlying
      bowel or renal dysfunction.

PMID- 8133820
TI  - Covert video surveillance in Munchausen syndrome by proxy. Ethical compromise or
      essential technique?
AB  - It has been suggested that the use of covert video surveillance in suspected
      cases of Munchausen syndrome by proxy should be curtailed as it represents a
      breach of trust between health care workers, parents and children. We present a
      case of asphyxia induced by a mother, which was discovered by videotaping without
      consent. Two previous sudden infant deaths in the family over the preceding two
      years, with unexplained apnoeic episodes in the third child, were considered
      sufficiently suspicious to justify covert surveillance. Incontrovertible evidence
      of parentally induced asphyxia was obtained within 24 hours of full-time covert
      surveillance. Despite initial denial, the mother eventually pleaded guilty to
      manslaughter of the first infant and to causing grievous bodily harm to the third
      infant. We believe that alternative techniques, such as parent-child separation,
      or of videotaping only after informed consent has been obtained, could have
      compromised the investigation and produced unacceptable delays which would have
      placed the surviving infant at risk of serious morbidity or of death.

PMID- 8133821
TI  - Sexually transmitted diseases in the tropics.
AB  - Several sexually transmitted diseases are endemic in the tropics. The morbidity
      and mortality from the human immunodeficiency viruses (HIV-1 and HIV-2) alone now
      rival that caused by Plasmodium falciparum malaria in several African and Asian
      nations. The genital ulcers of chancroid and syphilis facilitate the sexual
      transmission of HIV. Within the last two decades, the bacteria causing chancroid
      and gonorrhoea throughout the world have acquired plasmids that mediate bacterial
      resistance to penicillins and other antibiotics. This has significantly increased
      the costs of treatment. There is little prospect that the prevalence of
      gonorrhoea, chancroid, syphilis and HIV will decrease in the tropics in the near
      future without a global change in sexual behaviours and practices.

PMID- 8133822
TI  - Communicating well in general practice.
AB  - Evidence of deficiencies in communication skills in general practice abound,
      despite the importance with which such skills are regarded both within the
      profession and outside it. A qualitative assessment of associated literature over
      a 35-year period showed that good communication skills are associated with
      markers of better care and even of better health. Teaching communication skills
      to students is regarded as important, but it is not clear what form of education
      leads to better communication. Sufficient time is one of the most important
      elements; appropriate attitudes on the part of the clinician are probably
      important too. General practitioners can improve their care of patients by paying
      more attention to good communication and to understanding the consultation
      process.

PMID- 8133823
TI  - Rheumatology.

PMID- 8133824
TI  - Selective treatment decisions and the legal rights of very young infants.
AB  - Selective treatment of neonatal infants who are terminally ill or born with
      profound disabilities is becoming a controversial issue. The potential of medical
      technology, the practices of doctors and the expectations of parents have moved
      ahead of the law in this area. The interests of parents, children and medical
      practitioners would be better served by a clarification of the law. Legal change
      should be based on an ethical and moral foundation. The application of the "best
      interests" test should be given further consideration.

PMID- 8133825
TI  - Mass screening programs for prostatic carcinoma.

PMID- 8133826
TI  - Paracelsus.

PMID- 8133827
TI  - The use of poorly validated expensive technology.

PMID- 8133828
TI  - Depression in the elderly.

PMID- 8133829
TI  - Doctors should not give syringes to children.

PMID- 8133830
TI  - C1-esterase inhibitor concentrate prevents upper airway obstruction in hereditary
      angio-oedema.

PMID- 8133831
TI  - Marlboro Man.

PMID- 8133832
TI  - Screening for neural tube defects.

PMID- 8133833
TI  - [The role of thyroid hormones in the fetal period: a problem still discussed].

PMID- 8133834
TI  - [Liver transplant in children: comments and legislative proposal].
AB  - Having examined the literature on this subject, the authors raise the problem of
      segmentary liver transplant from a liver donor to a pediatric patient. They
      evaluate the current Italian legislation regarding the donation of organs and on
      the basis of foreign experience they draft a possible amendment to the law
      currently in force.

PMID- 8133835
TI  - [Influence of maternal smoking on cord serum IgE levels in newborns].
AB  - Allergic diseases are among the most common diseases in childhood and their
      prevalence is 14%. One of the most important pathogenetic factors is the ability
      to produce IgE and the measurement of cord serum IgE seems to be very important
      for early detection of newborns at risk. Besides, cigarette smoke, among the
      environmental factors, has been demonstrated to influence the immunologic system,
      inducing an increase in IgE production. The aim of this study is to evaluate
      fetal production of IgE in newborns with a family history of atopy and whose
      mother has been smoking during pregnancy. The measurement of cord serum IgE has
      been performed in 215 at term newborns (weight at birth > 2500 g, Apgar score at
      5' > 7). A careful history has been obtained with particular regard at the
      presence of familiarity for allergies and a cigarette smoking during pregnancy.
      According to the history, children have been divided in 3 groups: Group 1: 126
      newborns without familiar history of allergy and born from no smoking mothers
      (control group); Group 2: 46 newborns with familiar history for allergy and born
      from no smoking mothers; Group 3: 43 newborns without familiar history for
      allergy born from smoking mothers. The II and III groups of newborns present
      total IgE levels on cord serum significantly higher than the control group.
      Besides a positive correlation between the number of cigarettes smoked during
      pregnancy and the value of cord serum IgE has been detected. It is well known
      that both genetic and environmental factors play an important role in the
      pathogenesis of allergic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133836
TI  - [The child of hypertensive mother in pregnancy or EPH-gestosis: a long follow
      up].
AB  - Twenty three children of gestosic mothers or those suffering just from
      hypertension during pregnancy were studied: the follow-up covered an extremely
      long period (up to a maximum age of 15) to see if, in time, problems related to
      blood pressure, growth or of a neurological nature would arise. The results have
      shown that only weight problems exist, with 21.7% of the subjects being obese, a
      percentage which is, however, similar to that found among students of the same
      age group in a Roman school in the same area. It is important to point out the
      lack of cases of hypertension among these children, (which is probably due to the
      dietary advice given to them) all of whom have family hypertension and
      neurological history (taking into consideration that 34.7% were premature). We
      conclude by emphasizing the importance of long term paediatric follow-up which
      allows us to be optimistic towards the maternal pathology in as much suitably
      treated.

PMID- 8133837
TI  - [Vulvo-vaginitis in pediatric age].
AB  - In pediatric gynecology, inflammatory vulvo-vaginitis are very common. Their
      diagnosis cannot be based either on the symptoms (itching or pain) or on the
      signs (leucoxanthorrhea) for these classifications are "non-specific". At the
      Consulting Room of pediatric gynecology of the Vittore Buzzi Hospital, 215 "non
      specific" vulvo-vaginitis cases have been analyzed through bacteriological and
      microscopical examinations of vaginal secretions. The vaginal tampon resulted
      negative in 53% of the cases and positive in the remaining 47%. Comparing these
      results with microscopical examinations we obtain: 81.8% of sensibility, 77.4% of
      specificity, 87.8% of negative predictive value and 62.2% of positive predictive
      value. In particular, this last figure is influenced by the high number of false
      positives of the vaginal tampons, due to the growth "in vitro" of opportunist
      germs momentarily quiescent "in vivo". Thus it is useful to associated the
      microscopical examination (that will indicate all the cases in need of treatment)
      and the bacteriological examination (that will indicate the right cure).

PMID- 8133838
TI  - Description of a patient with difficult nosological classification: Goldenhar
      syndrome or Townes-Brocks syndrome?
AB  - The authors report a case of difficult nosological classification. The patient, a
      4-year-old female shows facial asymmetry, preauricular tags, anterior
      displacement of the anus and rib anomalies. Some of these clinical signs are
      present both in the Goldenhar syndrome and in the Townes-Brocks syndrome.

PMID- 8133839
TI  - [Abetalipoproteinemia: case report].
AB  - The abetalipoproteinemia is a recessively inherited defect in the formation of
      the proteins coating chylomicrons. Their absence compromises the transport of
      absorbed fats out of the enterocytes into the lymphatic system and the general
      circulation. Clinical features include steatorrhea, retarded growth,
      acanthocytosis of erythrocytes, retinitis pigmentosa and a chronic progressive
      neurological disorder with ataxia. We describe here the case of a 3 year old
      girl.

PMID- 8133840
TI  - [Perineal ectopic testis. Report of seven cases].
AB  - Between 1973 and 1993 7 perineal testis are observed and operated on in our
      surgical department. The perineal testis is a rare ectopic testis probably caused
      by some mechanical obstacles in the entrance of the testis in the scrotum. A
      diagnosis is easy if also the less frequent localizations of testicular ectopia
      are palpated. Surgery must be precociously performed or, in case of late
      discovery, upon diagnosis effected because the perineal testis is particularly
      subject to traumathisms. Orchiopexy is easy to perform, the results are good and,
      if promptly treated, this form of ectopia has an excellent prognosis of
      fertility.

PMID- 8133841
TI  - [Pancreatitis associated with salmonella].
AB  - There is no general agreement about the possibility that pancreatitis could be
      regarded as a clinical complication of Salmonella infection. We report 2 cases of
      salmonellosis WHO were admitted to our Department for clinical and biological
      signs of pancreatitis. Our observation agrees with other reported cases,
      suggesting that patients affected by salmonellosis with upper abdominal pain
      should be investigated for concomitant pancreatitis; on the other hand in
      patients suffering from diarrhea with hyperamylasaemia, salmonellosis should be
      considered as a likely explanation for their clinical condition.

PMID- 8133842
TI  - [Diaphragmatic eventration in pediatric age: indications to surgery and results].
AB  - Indication for surgical treatment and its results are reported in 17 consecutive
      cases of diaphragmatic eventration in pediatric age. Fourteen of the patients are
      males and 3 are females. Eleven of them had a right eventration 6 had a left
      eventration. Three of the patients were new-born, 13 were aged from 6 months to 3
      years and 1 was aged 6 years. Two patients had gastroesophageal reflux, 1 had
      right intralobar pulmonary sequestration, and another had inguinal hernia. In 2
      of the new-born the eventration was caused by a phrenic nerve palsy (in 1 case
      resulting from birth trauma, while in the other one resulting from multiple
      thoracentesis). In this last patient surgical treatment wasn't performed, and
      restitutio ad integrum was observed in 4 weeks' time. The indication for surgical
      treatment in 2 new-born patients was persistent polypnoea and dyspnoea
      unresponsive to medical treatment, in 12 of the patients were relapsing
      bronchitis and bronchopneumonia. Moreover 1 patient with few symptoms but with
      important diaphragmatic eventration was operated. In all the patients a
      diaphragmatic plication with fixing of the diaphragmatic plica to the ribs was
      performed through a thoracic approach. Neither complication or deaths were
      noticed. There was an immediate remission of the symptomatology in all the cases
      examined. No relapse of eventration or restarting of the symptomatology was found
      during a follow-up for a period of 2 to 8 years.

PMID- 8133843
TI  - [Use of the polymerase chain reaction to identify Helicobacter pylori in clinical
      material].
AB  - A new system for the detection of Helicobacter pylori DNA, based on the method of
      directed amplification, has been developed. Primers for specific detection of H.
      pylori were selected from a nucleotide sequence of 16 S-p RNA. The sequences of
      the primers had a few nucleotide substitutions as compared with the sequences of
      closely related microorganisms. An essential condition for the attainment of
      reaction specificity was the rise of annealing step temperature to 66 degrees C.
      Sensitivity of the system was in the range of 3 to 30 fg of DNA, or 20 to 100
      bacterial cells. Using the proposed system for the detection of H. pylori DNA
      clinical specimens (stomach biopsy sample, gastric juice and wash-offs of oral
      cavity), obtained from 49 patients with antral gastritis, were analyzed. The
      method of H. pylori detection in clinical specimens using polymerase chain
      reaction (PCR) turned out to be more sensitive compared with microbiological
      tests. By application of PCR H. pylori DNA was detected in subgingival pockets.

PMID- 8133844
TI  - [Development of a test system for detecting Leptospira interrogans using the
      polymerase chain reaction].
AB  - Based on polymerase chain reaction a test-system has been elaborated permitting
      one to identify the leptospirae of the most common serogroups
      (Icterohaemorrhagiae, Canicola, Javanica, Ballum, Pyrogenes, Pomona, Habdomadis,
      Sejroe, Tarassovi) of the species Leptospira interrogans. Sensitivity of the
      technique is 1-10 cells in a sample. The specificity of the system has been shown
      to depend on the temperature of the primers annealing. The elaborated system
      exceeds all other systems for leptospiral identification in sensitivity. It is
      prospective for leptospiral identification in biological liquids aimed at early
      diagnosis of leptospiroses and in the studies of leptospiral persistence in host
      organisms in the saprophitic phase of life cycle.

PMID- 8133845
TI  - [A polymerase chain reaction method for studying host persistence of pathogenic
      leptospira].
AB  - Polymerase chain reaction has for the first time been shown to be applicable to
      indication of Leptospira interrogans in the organs of infected animals with acute
      or chronic leptospirosis (on the model of golden syrian hamsters). Polymerase
      chain reaction is superior to microscopic and bacteriological analyses in
      identification of leptospirae in organ suspensions. The sensitivity of the
      technique is 1-10 cells per sample in studies of kidney or brain suspensions or
      100-1000 cells in studies of liver suspensions.

PMID- 8133846
TI  - [Protective activity of the recombinant strain Salmonella minnesota R595/GSA,
      synthesizing the plague capsule antigen in experimental plague in mice].
AB  - Protective properties of the recombinant strain Salmonella minnesota R595/GSA in
      experimental murine plague were studied. The recombinant vaccine ReFI possesses a
      high protective activity against plague with the level of survival, the LD50,
      indexes of immunity and the mean periods of animal death not inferior to those of
      the commercial vaccine. The protective properties of the live and killed
      recombinant ReFI vaccines in experimental murine plague are practically
      identical. The experimental recombinant vaccine is efficient at infecting doses
      up to 10(5) CFU. The live and killed vaccines are nontoxic for mice at doses up
      to 10(10) CFU.

PMID- 8133847
TI  - [Species-specific detection of Listeria monocytogenes by directed DNA
      amplification].
AB  - A highly sensitive species-specific test system which allows detection Listeria
      monocytogenes in animal tissues is elaborated using the principle of a polymerase
      chain reaction. The potentialities of its application were studied in the
      conditions of experimental infection of animals. It is shown that while the
      procedure of detection is relatively simple and fast, the test system is as
      sensitive and specific as traditional microbiological methods.

PMID- 8133848
TI  - A chromosome map of Shigella flexneri with the loci related to pathogenicity.

PMID- 8133849
TI  - [A species-specific DNA probe for identifying toxic strains of anthrax
      pathogens].
AB  - On the plasmid DNA pOX01 of the anthrax pathogen two BamHI fragments were
      localized which facilitate detection of the Bacillus anthracis strains carrying
      pXO1 replicon. These fragments, after complete hydrolysis of plasmid DNA by
      HindIII, were cloned on the vector plasmids pUC19 and pBR322 by the "shot-gun"
      method in Escherichia coli cells. It is shown that the 900 bp BamHI/HindIII
      fragment from the pZAT1 recombinant plasmid has an ability for specific
      hybridization with DNA of toxigenic strains of B. anthracis and could be used as
      species-specific anthracic DNA probe which identifies toxigenic strains of the
      anthrax pathogen differentiating it from the other species of Bacillus genus as
      well as from the bacteria of other taxonomy groups.

PMID- 8133850
TI  - [Determination of the nucleotide sequence of the Russian variant of the hepatitis
      C virus].
AB  - From a blood serum of patients with chronic posttransfusional non-A, non-B
      hepatitis the genomic RNA of hepatitis C virus (HCV) was isolated. Using RT-PCR
      (reverse transcription-polymerase chain reaction) there were synthesized and
      cloned cDNA fragments, representing 3 regions of the genome of a new virus
      isolate (HCV-R): 5'-nontranslating region, a core gene and a part of the
      nonstructural region NS3/NS4. Analysis of the nucleotide and of the amino acid
      sequences of a core and NS3/NS4 regions revealed significant difference between
      isolates from Russia (HCV-R) and from Japan (HCV-J). Nucleotide sequence homology
      between them was 90.0-90.87%, while homology between Russian and American
      isolates (USA-PT) complised 95.27-97.32%. No essential variations were found in
      the nucleotide sequences of 5'-nontranslating region of all three HCV isolates.

PMID- 8133851
TI  - [Supercopy plasmid based on the replicon from the temperate N15 bacteriophage].
AB  - Mini-plasmids, based on the N15 temperate bacteriophage replicon, are described.
      One of these, N15-203 linear 13.8 kb plasmid, has anomalously high copy number-
      more than 250 per one bacterial chromosome and the amount of plasmid DNA
      comprises about half of the total DNA of a cell. This property of N15-203 plasmid
      is realized only in the strain lysogenic for a N15 phage and is lost for the
      circular deletion versions of N15-203. The efficiency of transformation of E.
      coli C (N15) strain is essentially the same for N15-203 and pUC4K plasmids.
      Insertion of foreign DNA with a size up to 20 kb into BgIII cloning site of N15
      203 plasmid does not decrease significantly efficiency of transformation
      calculated per number of DNA molecules and the total amount of plasmid DNA in a
      cell. N15-203 plasmid may be used as a vector for molecular cloning of relatively
      large DNA fragments, and in those biotechnology processes when productivity
      depends on a vector's copy number.

PMID- 8133852
TI  - Absence of sex bias in the referral of patients for cardiac catheterization.
AB  - BACKGROUND: It has been suggested that women with clinical evidence of coronary
      artery disease are less often referred for cardiac catheterization than are men.
      To determine whether there is sex-related bias in referral for cardiac
      catheterization, we prospectively studied a cohort of 410 symptomatic outpatients
      (280 men and 130 women) who were being evaluated with exercise testing for
      possible-coronary artery disease. METHODS: Before the patients underwent exercise
      testing, 15 cardiologists from an academic medical center were asked to predict
      the probability that the patients they saw in the cardiology clinic would have
      angiographic evidence of any obstructive coronary disease (stenosis of 75 percent
      or more); the probability of severe coronary disease (three-vessel or left main
      coronary artery disease); the probability of left main coronary artery disease;
      and the probability of survival one, three, and five years after the evaluation.
      Similar predictions were generated by previously validated statistical models
      with use of data collected before exercise testing from the history, physical
      examination, and 12-lead electrocardiography with the patient at rest. RESULTS:
      Overall, women were referred for cardiac catheterization significantly less often
      than men (18 percent vs. 27 percent, P = 0.03). As compared with men, women had a
      significantly lower pretest probability of coronary disease (as estimated by
      their physicians) and a lower rate of positive exercise-test results. After
      accounting for differences in these two factors, sex was not an independent
      predictor of referral for catheterization. Comparing physicians' estimates of
      outcome with those generated by the statistical models revealed no evidence that
      the physicians were underestimating the risk of coronary disease in women.
      Furthermore, physicians' predictions did not underestimate the probability of any
      obstructive coronary disease in men and women who subsequently underwent
      catheterization. CONCLUSIONS: Academic cardiologists made appropriately lower
      pretest predictions of categories of disease in women with possible coronary
      artery disease than in men, and these assessments, along with women's lower rate
      of positive exercise tests, rather than bias based on sex, accounted for the
      lower rate of catheterization among women.

PMID- 8133854
TI  - Brief report: combined liver and heart transplantation for end-stage iron-induced
      organ failure in an adult with homozygous beta-thalassemia.

PMID- 8133853
TI  - A controlled trial of intravenous immune globulin to reduce nosocomial infections
      in very-low-birth-weight infants. National Institute of Child Health and Human
      Development Neonatal Research Network.
AB  - BACKGROUND: Nosocomial infections are a major cause of morbidity and mortality in
      premature infants. As a rule, their low serum gamma globulin levels at birth
      subsequently decline to hypogammaglobulinemic values; hence, prophylactic
      administration of intravenous immune globulin may reduce the rate of hospital
      acquired infections. METHODS: In this prospective, multicenter, two-phase
      controlled trial, 2416 infants were stratified according to birth weight (501 to
      1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune
      globulin group (n = 1204) or a control group (n = 1212). Control infants were
      given placebo infusions during phase 1 of the study (n = 623) but were not given
      any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth
      were given 900 mg of immune globulin per kilogram of body weight, and infants
      weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The
      immune globulin infusions were repeated every 14 days until the infants weighed
      1800 g, were transferred to another center, died, or were sent home from the
      hospital. RESULTS: Nosocomial infections of the blood, meninges, or urinary tract
      occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the
      immune globulin group and 231 (19.1 percent) in the control group (relative risk,
      0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5
      percent of the immune globulin recipients and 17.2 percent of the controls.
      During phase 1 the rate of nosocomial infections was 13.4 percent in the immune
      globulin group and 17.8 percent in the control group; the respective rates during
      phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included
      gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and
      candida species (16.0 percent). Adverse reactions were rarely observed during the
      infusions. Immune globulin therapy had no effect on respiratory distress
      syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of
      hospitalization, or mortality. The incidence of necrotizing enterocolitis was
      12.0 percent in the immune globulin group and 9.5 percent in the control group.
      CONCLUSIONS: Prophylactic use of intravenous immune globulin failed to reduce the
      incidence of hospital-acquired infections in very-low-birth-weight infants.

PMID- 8133855
TI  - Images in clinical medicine. Adenoma of the sigmoid colon.

PMID- 8133856
TI  - Immune mechanisms of cardiac disease.
AB  - It is evident that cellular infiltration can affect cardiac structure and
      function in a variety of disease states. Myocardial contractility can be impaired
      by cell-mediated injury or local release of cytokines. The study of immune
      cardiac disease has entered a period of rapid expansion that should be
      characterized by delineation of the mechanisms by which immune cells and factors
      localize in the myocardium, modulate myocyte function, and remodel myocardial
      architecture (Fig. 2). This new knowledge should result in the ability to target
      specifically both the pathways by which cardiac contractility is impaired by
      chronic inflammation and the sustained immune reactivity to cardiac antigens that
      underlies chronic myocardial inflammation. Nonspecific therapeutic interventions
      directed at congestive heart failure, currently the only acceptable approach to
      the treatment of immune myocarditis, should then serve a more ancillary function
      in the context of the use of rationally designed drugs. Such drugs could, for
      example, be specifically targeted to inhibiting the trafficking of leukocytes
      into the heart or the effects of their subsequent activation within the
      myocardium.

PMID- 8133857
TI  - Chemotherapy for colorectal cancer.

PMID- 8133858
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 16-1994. A 57-year-old woman with a mass in the right atrium.

PMID- 8133859
TI  - Prenatal diagnosis--why is 35 a magic number?

PMID- 8133860
TI  - Are body iron stores related to the risk of coronary heart disease?

PMID- 8133861
TI  - The infertile couple.

PMID- 8133862
TI  - The infertile couple.

PMID- 8133863
TI  - The infertile couple.

PMID- 8133864
TI  - The infertile couple.

PMID- 8133865
TI  - Triggering of acute myocardial infarction by exercise.

PMID- 8133866
TI  - Triggering of acute myocardial infarction by exercise.

PMID- 8133867
TI  - Guns in the home.

PMID- 8133868
TI  - Polyp of the appendix.

PMID- 8133869
TI  - Cardiac surgery at 87.

PMID- 8133870
TI  - Acute vanishing bile duct syndrome after interferon therapy for recurrent HCV
      infection in liver-transplant recipients.

PMID- 8133871
TI  - Who wants a healthful breakfast?

PMID- 8133872
TI  - Health care reform and graduate medical education.

PMID- 8133873
TI  - Clinton courts research hospitals.

PMID- 8133874
TI  - Drugs bill to rein in profits.

PMID- 8133875
TI  - Kessler adds heat to smoking debate.

PMID- 8133876
TI  - Japan's E. coli genome project falling short.

PMID- 8133877
TI  - Commercial family planning for India.

PMID- 8133878
TI  - Monsanto sues over BST.

PMID- 8133879
TI  - AIDS plagued by journalists.

PMID- 8133880
TI  - Cancer institute treated unfairly.

PMID- 8133881
TI  - Sex determination.

PMID- 8133882
TI  - T-cell selection. A little of what you fancy ...

PMID- 8133883
TI  - Palaeoanthropology. Variable but singular.

PMID- 8133884
TI  - Transcription. Simplifying the complex.

PMID- 8133885
TI  - Migration of muscle cells.

PMID- 8133886
TI  - Longevity and testosterone.

PMID- 8133887
TI  - Physiological consequences of loss of plasminogen activator gene function in
      mice.
AB  - Indirect evidence suggests a crucial role for the fibrinolytic system and its
      physiological triggers, tissue-type (t-PA) and urokinase-type (u-PA) plasminogen
      activator, in many proteolytic processes. Inactivation of the t-PA gene impairs
      clot lysis and inactivation of the u-PA gene results in occasional fibrin
      deposition. Mice with combined t-PA and u-PA deficiency suffer extensive
      spontaneous fibrin deposition, with its associated effects on growth, fertility
      and survival.

PMID- 8133888
TI  - Design and synthesis of multi-haem proteins.
AB  - A water-soluble, 62-residue, di-alpha-helical peptide has been synthesized which
      accommodates two bis-histidyl haem groups. The peptide assembles into a four
      helix dimer with 2-fold symmetry and four parallel haems that closely resemble
      native haems in their spectral and electrochemical properties, including haem
      haem redox interaction. This protein is an essential intermediate in the
      synthesis of molecular 'maquettes', a novel class of simplified versions of the
      metalloproteins involved in redox catalysis and in energy conversion in
      respiratory and photosynthetic electron transfer.

PMID- 8133889
TI  - The first skull and other new discoveries of Australopithecus afarensis at Hadar,
      Ethiopia.
AB  - The Hadar Formation in Ethiopia is a prolific source of Pliocene Hominidae
      attributed to the species Australopithecus afarensis. Since 1990, three seasons
      of field work have contributed 53 new specimens to the hominid inventory from
      Hadar, including the first fairly complete adult skull. Ranging from 3.0 to 3.4
      million years in age (Fig. 1), the new specimens bear on key debates in hominid
      palaeontology, including the taxonomic implications of sample variation and the
      reconstruction of locomotor behaviour. They confirm the taxonomic unity of A.
      afarensis and constitute the largest body of evidence for about 0.9 million years
      of stasis in the earliest known hominid species.

PMID- 8133890
TI  - Matrix correlation tests support a single origin for modern humans.
AB  - The debate over human origins has focused on two competing theories. The single
      African origin model holds that anatomically modern Homo sapiens evolved in
      Africa 100,000-200,000 years ago. Members of this population migrated out of
      Africa, replacing archaic human groups through Asia and Europe, with racial
      differentiation occurring within the past 100,000 years. The alternative regional
      continuity model proposes continuous evolution over the past million years, with
      racial variation developing early, and similar modern human traits developing in
      all regions as the result of worldwide gene flow. The persistence of specific
      morphological features within regions over the past million years supports
      regional continuity, whereas the identification of anatomically modern fossil
      specimens from Africa and the Levant 50-60,000 years before they are found
      elsewhere, provides support for a single origin. I give here the first
      quantitative test of the fossil evidence for each of these models. Results
      support a single African and/or Levantine origin for modern humans.

PMID- 8133891
TI  - Bcl-2 expression promotes B- but not T-lymphoid development in scid mice.
AB  - Expression of antigen receptors is vital for the development of B and T
      lymphocytes. In mice with the scid mutation, which are unable to make productive
      rearrangements of their immunoglobulin and T-cell receptor (TCR) genes,
      lymphopoiesis aborts at an early stage. The death of the immature lymphocytes by
      apoptosis is postulated to result from a failure to receive a survival signal
      induced by receptor engagement. Consistent with this hypothesis, introduction of
      immunoglobulin or TCR transgenes into scid mice promoted an increase in B- or T
      lymphoid cells, respectively. As the protein encoded by the bcl-2 gene can
      inhibit cell death, we tested whether lymphopoiesis could be rescued in scid mice
      by crossing in a bcl-2 transgene. Strikingly, the bcl-2/scid mice accumulated
      almost normal numbers of B-lymphoid cells which lacked surface immunoglobulin but
      expressed markers of maturity. T-cell development remained blocked. Introducing a
      TCR transgene enabled bcl-2/scid mice to develop normal numbers of CD4+8+
      thymocytes even in the absence of immunological selection, suggesting that T
      cells become competent to respond to bcl-2 protein only after the TCR complex is
      displayed at the cell surface.

PMID- 8133892
TI  - Early determination of a mouse somatosensory cortex marker.
AB  - The mammalian neocortex is subdivided into functionally distinct areas differing
      in cytoarchitecture and connectivity. Areal specification is thought to occur
      late in development and to be controlled by extrinsic cues, particularly thalamic
      afferents. We have produced a transgenic mouse line in which beta-galactosidase
      expression in the neocortex is largely restricted to layer-IV neurons of the
      somatosensory area. Transgene expression in these mice may be considered as an
      intrinsic marker of a somatosensory cortex identity. We investigated whether the
      fate of pieces of embryonic cortex from transgenic embryos is modified after
      transplantation to ectopic locations. Parietal or occipital cortex obtained on
      embryonic days 14-16 maintained their characteristics with respect to transgene
      expression after heterotopic transplantation to the cerebellum or neocortex of
      newborn hosts. This shows that the specification of neocortical areas involves a
      previously unsuspected early step of areal determination.

PMID- 8133893
TI  - Dynamics of brain activation during picture naming.
AB  - The cerebral representation of language, deduced from observing patients with
      brain lesions and from stimulations and recordings performed during brain
      surgery, has been further clarified by recent positron emission tomography and
      functional magnetic resonance imaging measurements. We now expand this static
      view into the dynamics of cortical activation using the accurate spatiotemporal
      resolution of whole-head magnetoencephalography. During picture naming, the
      conversion from visual to symbolic representation progressed bilaterally from the
      occipital visual cortex towards temporal and frontal lobes. Overt naming elicited
      the most widespread cortical activation. Some language-related sites also
      reacted, though more weakly or after a longer delay, during covert naming and
      even passive viewing.

PMID- 8133894
TI  - An RNA polymerase II holoenzyme responsive to activators.
AB  - RNA polymerase II requires multiple general transcription factors to initiate
      site-specific transcription. These proteins can assemble in an ordered fashion
      onto promoter DNA in vitro, and such ordered assembly may occur in vivo (Fig.
      1a). Some general transcription factors can interact with RNA polymerase II in
      the absence of DNA, however, suggesting that RNA polymerase II may also assemble
      into a multi-component complex containing a subset of initiation factors before
      binding to promoter DNA (Fig. 1b). Here we present evidence from the yeast
      Saccharomyces cerevisiae for such an RNA polymerase II holoenzyme, a multi
      subunit complex containing roughly equimolar amounts of RNA polymerase II, a
      subset of general transcription factors, and SRB regulatory proteins.
      Transcription by this holoenzyme is stimulated by the activator protein GAL4
      VP16, a feature not observed with purified RNA polymerase II and general
      transcription factors alone. We propose that the holoenzyme is a form of RNA
      polymerase II readily recruited to promoters in vivo.

PMID- 8133895
TI  - Determinants of repressor/operator recognition from the structure of the trp
      operator binding site.
AB  - On the basis of the crystal structure of the trp repressor/operator complex, it
      has been proposed that the specificity of the interaction can be explained not
      only by direct hydrogen bonding and non-polar contacts between the protein and
      the bases of its target DNA, but also by indirect structural effects and water
      mediated interactions. To understand the contribution of DNA structure and
      hydration in this context, the structure of the free DNA must be compared with
      its structure when complexed with the protein. Here we present the high
      resolution crystal structure of the trp operator region that is most important in
      the recognition process. By comparing the free and bound states of the DNA
      regulatory sequence, we show that the structure and hydration of the DNA target
      are important elements in its recognition by the repressor protein.

PMID- 8133896
TI  - A model for high-throughput automated DNA sequencing and analysis core
      facilities.

PMID- 8133897
TI  - Scientists moving into sales.

PMID- 8133898
TI  - Serotonergic modulation of neurotransmission in the rat subicular cortex in
      vitro: a role for 5-HT1B receptors.
AB  - We have studied the effect of serotonin on synaptic transmission in rat
      hippocampal subiculum slices. Electrical stimulation of the alveus induced a
      field potential in the subiculum. The non-NMDA glutamate receptor antagonist,
      NBQX (3 x 10(-6) mol/l) suppressed the response by 78%, indicating that the
      signal involves glutamatergic neurons. Application of serotonin suppressed (EC50
      = 3.6 x 10(-6) mol/l) the amplitude of the evoked potentials in a reversible,
      concentration-dependent manner. The responses to 5-HT were not altered after
      pretreatment with the 5-HT uptake blocker, fluvoxamine (10(-5) mol/l) or a
      combination of the MAO inhibitor pargyline (10(-5) mol/l) and ascorbic acid (10(
      4) mol/l). The responses to 5-HT were also unaffected by pretreatment with the 5
      HT1A selective antagonist NAN-190 (10(-6) mol/l), the 5-HT2A antagonist
      ketanserin (10(-6) mol/l) or the 5-HT3/5-HT4 antagonist ICS 205-930 (10(-6)
      mol/l). The 5-HT1B selective agonist CP 93,129 mimicked the effects of serotonin,
      but was more potent (EC50 4.1 x 10(-7) mol/l). The 5-HT1B receptor antagonist,
      (+/-)21-009 (3 x 10(-7) mol/l), antagonized the response to 5-HT and CP 93,129
      with a pKB value of 7.1 and 7.2, respectively. These results suggest that the
      effect of 5-HT in the rat subiculum is mediated by 5-HT1B receptors.

PMID- 8133899
TI  - 5-Hydroxytryptamine (5-HT) contracts the guinea-pig isolated iliac artery via 5
      HT1-like and 5-HT2 receptors.
AB  - The characterization of 5-hydroxytryptamine (5-HT) receptors mediating
      contractions of the guinea-pig isolated iliac artery was studied when the basal
      tone was slightly increased by prostaglandin F2 alpha (PGF2 alpha). In the
      presence of ketanserin (1 mumol/l), 5-HT and several 5-HT receptor agonists
      induced contractile responses with the rank order of agonist potency: 5-HT = 5
      carboxyamidotryptamine (5-CT) = lysergol > ergometrine = methylergometrine > RU
      24969 approximately 5-methoxytryptamine (5-MeOT) > methysergide > sumatriptan >
      tryptamine. Concentration-effect curves to the ergot alkaloids, lysergol,
      ergometrine, methylergometrine and methylsergide, were biphasic. In the presence
      of ketanserin (1 mumol/l), contractile responses to 5-HT, 5-CT, RU 24969, 5-MeOT,
      sumatriptan and tryptamine were antagonized by methiothepin (30 nmol/l) and
      flesinoxan (3 mumol/l) with approximate pKB values of 8.5-9.0 and 6.0-6.3,
      respectively. The first phase of contraction produced by the ergot alkaloids,
      lysergol, ergometrine, methylergometrine and methysergide, were blocked by
      methiothepin (30 nmol/l) and flesinoxan (3 mumol/l), respectively, with
      approximate pKB values about 8.4-8.7 and 6.2-6.4, respectively. The mechanism
      underlying the second phase of contraction remains to be established. Maximum
      responses of the concentration-effect curves to 5-HT (1 nmol/l-1 mumol/l) were
      concentration-dependently depressed by ketanserin (1 nmol/l-1 mumol) and
      spiperone (30 nmol/l-0.3 mumol/l) and reached approximately 60% of the 5-HT
      maximum response in the presence of ketanserin (1 mumol/l) and spiperone (0.1
      mumol/l), respectively. Agonist potency of 5-HT was not affected by the
      antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133901
TI  - The effect of carbidopa on the pharmacokinetics and metabolism of intravenously
      administered levodopa in blood plasma and skeletal muscle.
AB  - The effect of carbidopa on the pharmacokinetics and metabolism of levodopa (L
      dopa) in blood plasma and skeletal muscle extracellular fluid (ECF) has been
      studied by repeated measurements in one beagle dog. The administration of a
      single dose of L-dopa (25 mg/kg i.v.) without carbidopa pretreatment (controls)
      resulted in an increase in the concentrations of L-dopa and 3-O-methyldopa (3
      OMD) in blood plasma and skeletal muscle ECF dialysates. This effect was clearly
      potentiated for L-dopa in blood plasma (186% increase in AUC) and 3-OMD in
      skeletal muscle dialysates (108% increase in AUC) after pretreatment with
      carbidopa (100 mg/day). In addition, carbidopa prolonged the half-life of the
      elimination of L-dopa in blood plasma by 48% and in skeletal muscle ECF by 66%
      but did not influence its blood plasma distribution half-life (t 1/2 alpha = 0.17
      h). The elimination half-life of L-dopa in the controls was higher in muscle (t
      1/2 beta = 1.76 h) than in blood plasma (t 1/2 beta = 0.50 h). Carbidopa
      pretreatment resulted in a relatively small increase (29%) in the L-dopa content
      of skeletal muscle ECF as indicated by the AUC. The accumulation of 3-OMD in
      muscle dialysates, in contrast to that in plasma, was significantly enhanced
      after the administration of L-dopa following treatment with carbidopa. In the
      control experiments, dopamine (DA) was detectable only in the dialysates from
      muscle ECF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133900
TI  - Cell-specific coupling of the cloned human 5-HT1F receptor to multiple signal
      transduction pathways.
AB  - We recently described the cloning of a fifth member of the 5-hydroxytryptamine (5
      HT)1 (serotonin1) receptor class that inhibits adenylyl cyclase, namely the human
      5-HT1F receptor (Adham et al. 1993a). In the present study we have examined in
      greater detail the functional coupling of the 5-HT1F receptor in two different
      cell lines, NIH-3T3 and LM(tk-) fibroblasts (receptor densities of 1.7 and 4.4
      pmol/mg protein, respectively). The maximal inhibitory response elicited by 5-HT
      was significantly greater in NIH-3T3 as compared to LM(tk-) cells, whereas the
      EC50 values were comparable. To investigate the relationship between receptor
      occupancy and inhibition of cAMP accumulation mediated by 5-HT1F receptors in NIH
      3T3 cells (and hence the degree of receptor reserve), we used the irreversible
      receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The
      half-maximal response required only about 10% receptor occupancy, consistent with
      a receptor reserve of 90% (88 +/- 2.1%, n = 4) for 5-HT-induced inhibition of
      FSCA. Despite the presence of such a high degree of receptor reserve, a range of
      intrinsic activities was displayed by structurally diverse classes of compounds.
      For example, sumatriptan and lysergol were as efficacious as 5-HT itself and thus
      acted as full agonists, whereas metergoline and 1-NP behaved as partial agonists
      and as shown previously (Adham et al. 1993a), methiothepin was a silent
      antagonist (Kb = 438 nM). We have also investigated activation of additional
      signal transduction pathways by the 5-HT1F receptor and found that the responses
      differ in the two cell lines with respect to stimulation of phospholipase C. For
      example, in NIH-3T3 cells no elevation of inositol phosphates (IP) of [Ca2+]i was
      observed even at very high agonist concentrations (100 microM). In contrast, in
      LM(tk-) cells concentrations of 5-HT as low as 10 nM induced stimulation of IP
      and a rapid increase of [Ca2+]i. The 5-HT1F receptor failed to alter arachidonic
      acid release in either cell line. The maximal increase in IP accumulation in
      LM(tk-) cells was modest, averaging about 100% above basal. The increases of IP
      and [Ca2+]i required 5-HT concentrations less than one order of magnitude greater
      than those inhibiting FSCA (EC50 = 17, 55 and 8 nM, respectively), and both
      responses were blocked by 100 microM methiothepin. All three responses (cAMP, IP,
      and [Ca2+]i) were sensitive to pertussis toxin pre-treatment, suggesting the
      involvement of Gi/Go protein(s) in these signal transduction pathways.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8133902
TI  - COMT inhibitors and metabolism of fluorodopa enantiomers in aggregating cell
      cultures.
AB  - Organotypic primary cell cultures of fetal rat brain were used as a model system
      to study the effect of COMT inhibitors on the cerebral metabolic conversions of
      fluoro-DOPA enantiomers. The selective COMT inhibitors OR 486 and CGP 28014 were
      used in conjunction with 5F-L-DOPA, 6F-L-DOPA and 6F-D-DOPA as substrates.
      Methylation can be clearly reduced by application of OR 486 at nanomolar level,
      without inhibition of AADC and MAO. The uptake of the substrate is unchanged. CGP
      28014, already known to be active only in vivo, has no influence on the metabolic
      conversion rates of the fluoro-DOPA isomers. These results show that use of this
      culture system allows statement concerning the in vitro activity of COMT
      inhibitors. It has not been possible to show an increase of absolute levels of
      decarboxylation products due to inhibition of COMT, however, but the reduction in
      levels of methylated product itself may have significance for PET studies of the
      human brain.

PMID- 8133903
TI  - Distribution and characterisation of [3H]alpha,beta-methylene ATP binding sites
      in the rat.
AB  - Radioligand binding studies have been performed to study the distribution of the
      binding sites for the P2x purinoceptor selective agonist radioligand,
      [3H]alpha,beta-methylene ATP ([3H]alpha beta-meATP), in membranes prepared from
      various peripheral organs and several brain regions of the rat. In agreement with
      previous studies in the rat vas deferens, [3H]alpha beta-meATP labelled two
      populations of sites. One site exhibited high affinity for the ligand (Kd = 0.7
      nM; Bmax = 1012 fmol.mg-1 protein) while the other site exhibited lower affinity
      (Kd = 70.8 nM) and higher capacity (Bmax) = 7470 fmol.mg-1 protein). In
      competition studies, using a low concentration of radioligand (1 nM), the high
      affinity alpha beta-meATP binding sites in vas deferens membranes could be
      preferentially labelled (84-91%). Under these conditions, the P2x purinoceptor
      agonists, alpha beta-meATP and beta, gamma-methylene ATP, had the highest
      affinity with pIC50 values of 8.3 and 7.3 respectively. The P2y purinoceptor
      agonist, 2-methyl-thio-ATP (2-me-S-ATP), had lower affinity (pIC50 = 6.7), while
      uridine triphosphate, adenosine diphosphate and adenosine, agonists at the P2u,
      P2t and P1 purinoceptors, respectively, possessed low affinity (pIC50 values <
      5.6). In addition, the P2 purinoceptor antagonists, cibacron blue and suramin,
      inhibited binding over the same concentration range at which they behave as
      functional antagonists at the P2x purinoceptor. High and low affinity binding
      sites for [3H]alpha beta-meATP were also identified in a range of other
      peripheral tissues (spleen, heart and liver) and in several brain regions
      (striatum, cerebral cortex, hippocampus). In the spleen, heart, cerebral cortex
      and liver the Kd values at both the high affinity binding sites (Kd = 1-1.2 nM)
      and the low affinity binding sites (Kd = 98-158 nM) were similar to the
      respective Kd values at the high and low affinity binding sites in the vas
      deferens. In competition studies performed using a low concentration of
      radioligand (1 nM) these sites exhibited a similar pharmacological profile to
      that seen in the vas deferens. Detailed analysis of competition curves to several
      of the ATP analogues in each of the tissues revealed that the binding profile of
      the radioligand was complex since several compounds, and in particular ATP and 2
      me-S-ATP, identified a lower proportion of sites with high affinity than did
      alpha beta-meATP.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8133904
TI  - A role for computer simulation in solving the riddles of autoreceptor-mediated
      regulation of GABA release.
AB  - The autoreceptor-mediated control of GABA release was simulated on a personal
      computer using commercially available software (STELLA/ITHINK). The experimental
      data to be matched were taken from previous publications. A basic model was able
      to fairly accurately reproduce frequency dependencies of GABA release in the
      presence and absence of uptake inhibition as well as concentration-response
      curves for changes in release produced by the agonist, (-)-baclofen, or by
      relatively low concentrations of the antagonists, phaclofen and CGP 35348.
      Obvious mismatch was observed at high concentrations of a potent antagonist, at a
      stimulation frequency of 2 Hz. Whereas the experimental data indicate a 3-fold
      increase in release as compared to controls, simulation predicts a 7-fold
      increase. By adaptation of the model, simulation data were obtained indicating
      that this mismatch was not due to (a) the autoreceptor occurring as two subtypes
      with different affinities for antagonists, (b) the occurrence of an agonist and
      antagonist state of the autoreceptor, with the latter prevailing at low synaptic
      concentrations of endogenous GABA, and (c) overruling of uptake inhibition by
      markedly elevated synaptic GABA concentrations. On the other hand, a simple
      restriction of the amount of transmitter able to be released per time unit
      produced much better matching data. A refined model assuming a restricted
      replacement capacity for exocytotically emptied synaptic vesicles at their
      docking sites gave similar results. As a consequence, we shall attempt to address
      this possibility experimentally. Simulation can never prove a case in the
      positive sense. It can, however, help to exclude ill-matching solutions of a
      problem and to prioritize among possible ones, which then must be experimentally
      addressed. We found simulation with this user-friendly software extraordinarily
      useful, also and not least because it necessitates and stimulates very intense
      dealing with a subject.

PMID- 8133905
TI  - Activation of Cl- channels by avermectin in rat cultured hippocampal neurons.
AB  - The actions of the insecticide avermectin (AVM) were studied in rat cultured
      hippocampal neurons with patch-clamp techniques. Application of micromolar
      concentrations of AVM to voltage-clamped cells gave rise to whole-cell currents,
      which showed a slow time-course of activation in the order of 10 s, and wash-out
      periods of typically 20 min. Dose-response curves revealed a half-maximally
      activating AVM concentration (EC50) of 2.0 +/- 0.6 microM and a Hill coefficient
      of 1.5 +/- 0.9. The current activated by AVM was carried predominantly by Cl-
      ions, as demonstrated by ion-substitution experiments. The Cl- channel blocker
      picrotoxinin (100 microM) substantially but transiently reduced the AVM response.
      Outside-out patch recording showed that AVM opened Cl- channels with a
      conductance of 40 +/- 12 pS. The open-time distribution was characterized by two
      time constants of 11 ms and 259 ms. It is suggested that AVM directly activates
      Cl- channels in mammalian central neurons, which resemble the channels activated
      by the physiological transmitters GABA and glycine.

PMID- 8133906
TI  - Potentiation of acute opioid-induced respiratory depression and reversal of
      tolerance by the calcium antagonist nimodipine in awake rats.
AB  - The interaction between sufentanil, a mu-opioid agonist, and the Ca2+ antagonist
      nimodipine on respiration and on the development of opioid tolerance in awake
      rats has been analyzed. Our previous work demonstrated that chronic treatment
      with nimodipine together with sufentanil increases the analgesic potency of the
      opioid 50 fold. Therefore, we have investigated whether the opioid-induced
      respiratory depression is potentiated in parallel with the analgesia. Ventilation
      was measured by the whole body plethysmographic method. In naive rats, sufentanil
      (10-80 micrograms/kg) consistently induced a dose-dependent respiratory
      depression. Pretreatment with nimodipine (200 micrograms/kg) potentiated this
      effect but to a lesser extent than it potentiated analgesia. After chronic
      administration of the opioid (2 micrograms/h, 7 days) tolerance was manifested as
      a reduction in both the area under the time course curve and in the maximum
      effect. Nimodipine (1 microgram/h) administered concurrently with sufentanil for
      7 days counteracted the tolerance to respiratory depression but no additional
      potentiation was observed. These results demonstrate that the interaction between
      nimodipine and sufentanil is not limited to antinociception but also extends to
      respiratory depression. However, compared with analgesia, the clinical relevance
      of a potential increase in opioid-induced respiratory depression by nimodipine
      may be negligible.

PMID- 8133907
TI  - Propranolol unmasks class III like electrophysiological properties of
      norepinephrine.
AB  - Isolated perfused spontaneously beating rabbit hearts were treated with
      increasing concentrations of norepinephrine (0.01, 0.1, 0.5 mumol/l) either alone
      or in presence of propranolol (0.1 mumol/l). For analysis of the epicardial
      activation and repolarization process and epicardial mapping (256 unipolar leads)
      was performed. For each electrode the activation and repolarization time was
      determined. From these data the "breakthrough-points" (BTP) of epicardial
      activation were determined. At each electrode an activation vector (VEC) was
      calculated giving direction and velocity of the local excitation wave. The beat
      similarity of various heart beats (under NE) compared to control was evaluated by
      determination of the percentage of identical BTP and of similar VEC (deviation <
      or = 5 degrees). Moreover at each electrode the local activation recovery
      interval (ARI) and its standard deviation (of 256 leads, dispersion, DISP) were
      determined. Norepinephrine alone (0.01, 0.1, 0.5 mumol/l) led to an increase in
      left ventricular pressure, heart rate and DISP with concomitant frequency
      dependent reduction in ARI, and to changes in the epicardial activation pattern
      (reduction in BTP, VEC). We found that in the presence of propranolol (0.1
      mumol/l) norepinephrine prolonged ARI and reduced ARI-dispersion. This effect was
      not due to changes in heart rate. The disturbing effects on the activation
      pattern were diminished. These effects could be prevented by pretreatment with 1
      mumol/l prazosin. From these results we conclude, that norepinephrine prolongs
      the relative action potential duration via stimulation of alpha 1-adrenoceptor
      and enhances cellular coupling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133908
TI  - Inhibitory effects of propiverine on rat and guinea-pig urinary bladder muscle.
AB  - In muscle strips isolated from guinea-pig and rat urinary bladder, propiverine (3
      10 microM) inhibited carbachol-induced contractions in the presence of verapamil
      and Ca(2+)-induced contractions in excess K+ medium containing atropine,
      suggesting it has both anticholinergic and Ca2+ channel blocking actions. The
      Ca2+ channel blocking action was also demonstrated by recording inward Ca2+
      currents in single cells dispersed from both species. The inhibition of inward
      currents by propiverine was three times stronger in the rat than the guinea-pig,
      ID50 being 7 microM for rat and 21 microM for guinea-pig. The recovery of the
      current after washout was faster than that of mechanical inhibition. It is
      concluded that propiverine blocks not only muscarinic receptors, but also Ca2+
      channels at similar concentrations.

PMID- 8133909
TI  - The inhibitory effect of magnolol on cutaneous permeability in mice is probably
      mediated by a nonselective vascular hyporeactivity to mediators.
AB  - In the present study, we demonstrated the inhibitory effect of magnolol on the
      plasma leakage in passive cutaneous anaphylactic (PCA) reaction, neurogenic
      inflammation, dorsal skin and ear edema in mice. Hind-paw skin plasma
      extravasation caused by antidromic stimulation of the saphenous nerve was reduced
      in mice pretreated with magnolol, diphenydramine or methysergide, but not with
      indomethacin. Ear edema formation in the PCA reaction was reduced by magnolol in
      dose-dependent manner. In addition, histamine-, serotonin-, compound 48/80-,
      bradykinin- and substance P-induced ear edema in mice was also suppressed by
      magnolol. A dose- and time-dependency of the inhibitory effect of magnolol was
      demonstrated in histamine- and compound 48/80-induced dorsal skin edema. The
      maximal inhibitory effect produced by a single dose of magnolol (10 mg/kg)
      persisted for 1 h, and significant suppression lasted for at least 3 h. In
      compound 48/80-pretreated mice, the histamine content of the ear was greatly
      reduced. Bradykinin- and substance P-induced ear edema in compound 48/80
      pretreated mice was less severe than that seen in normal mice, but was still
      significantly reduced by magnolol pretreatment. Moreover, the inhibitory effect
      of magnolol was more marked than that of diphenhydramine combined with
      methysergide. These results suggest that the inhibitory effect of magnolol on
      local edema formation probably occurs through a nonselective inhibition on
      vascular tissue to prevent the permeability change caused by various mediators.

PMID- 8133910
TI  - Effect of a new de-N-acetyl-lysoglycosphingolipid on chemically-induced
      inflammatory bowel disease: possible mechanism of action.
AB  - A new, orally active de-N-acetylated lysoglycosphingolipid (WILD20) was evaluated
      as antiinflammatory agent using a model of chemically-induced inflammatory bowel
      disease (IBD) in the rat to mimic human ulcerative colitis and Chron's disease.
      IBD was induced by hapten trinitrobenzenesulphonic acid (TNB). WILD20, orally
      administered as preventive or curative, was demonstrated to be efficacious at
      daily dosages of 0.1-1 mg/kg for 4-5 days. Damage scores, body weight, spleen
      weight, colonic tissular levels of LTB4, myeloperoxidase (MPO) and
      malondialdehyde (MDA) are influenced and brought into parameters of normality.
      Histological observation demonstrated quicker healing, better repair, reduced
      inflammation, and poor eosinophil degranulation. The mechanisms underlying WILD20
      antiinflammatory effects were investigated: whereas WILD20 fails to show a direct
      effect on PKC, it reduces PKC translocation to the membrane; cellular PLA2 was
      consequently greatly reduced through this mechanism and thought to be responsible
      for WILD20 efficacy towards chemically-induced IBD.

PMID- 8133912
TI  - Evans blue blocks P2X-purinoceptors in rat vas deferens.
AB  - In rat vas deferens, Evans blue 100 microM increased contractions elicited by
      high K+ and by noradrenaline but markedly reduced contractions elicited by the
      P2X-purinoceptor-selective agonist alpha,beta-methylene ATP (3 microM). The
      concentration-response curve of alpha,beta-methylene ATP was shifted to the right
      by Evans blue 30 microM and the maximal contraction was increased. In tissues
      incubated with nifedipine 10 microM, Evans blue 100 microM tended to increase the
      residual contraction elicited by noradrenaline and abolished the residual
      response to alpha, beta-methylene ATP (3 microM). The concentration-response
      curve of alpha,beta-methylene ATP was progressively shifted to the right by
      increasing concentrations of Evans blue in the presence of nifedipine; maximal
      contractions were increased by Evans blue 10 and 30 but not 100 microM. From the
      shifts to the right caused by Evans blue 30 microM, apparent pKB values of 5.9
      (no nifedipine) and 6.0 (nifedipine present) were calculated. It is concluded
      that Evans blue blocks P2X-purinoceptors in rat vas deferens and in addition
      causes a non-receptor-specific enhancement of contractions.

PMID- 8133911
TI  - Differential distribution of calcineurin A alpha isoenzyme mRNA's in rat brain.
AB  - Specific antisense oligonucleotide probes for the alpha isoforms of the catalytic
      subunit (A-subunit) of calcineurin were prepared and the distribution of A alpha
      1 and A alpha 2 mRNA's has been studied in rat brain using in situ hybridization
      histochemistry. Clear regional differences have been observed for the A alpha 1
      and A alpha 2 isoforms. The predominant form, A alpha 1, was found to be
      preferentially expressed in the caudate putamen, the pyramidal cell layer of the
      hippocampus, specific cortical cell layers, the cerebellar granular cell layer
      and some other brain areas. On the other hand, the A alpha 2 isoform, although
      being generally less abundant than A alpha 1, gave an intense autoradiography
      signal in the dentate gyrus of the hippocampus and was the major transcript in
      the amygdala, the superior and the inferior colliculus, the central gray matter
      and the reticular formation. These regional differences might reflect specific
      functions exerted by the two alternatively spliced isoenzymes in the CNS and
      opens the perspective of interfering with defined calcineurin-dependent signal
      transduction pathways using isoform-specific compounds.

PMID- 8133913
TI  - Simplicity, who will pay, still unanswered questions in health care reform plan.

PMID- 8133914
TI  - Kurtzman: NKF focuses on research in response to declining federal support.

PMID- 8133915
TI  - Kolff, Nose compare mortality between Europe, Japan, and the U.S.. Interview by
      Robert H Carlson.

PMID- 8133917
TI  - Memoirs of a mature renal social worker.

PMID- 8133916
TI  - DePalma's corner. Law and truth, or all choices involve compromise.

PMID- 8133918
TI  - Adequacy of social work staffing in nephrology: a study.

PMID- 8133919
TI  - Changing assumptions about "disabilities" may improve rehabilitation in ESRD.

PMID- 8133920
TI  - The quandary of initiating, withdrawing dialysis.

PMID- 8133921
TI  - The protein dilemma: real food vs. liquid supplements.

PMID- 8133922
TI  - Sims: planning for the association's next quarter-century in nephrology nursing.

PMID- 8133923
TI  - Suttle: increasing awareness of NANT's purpose, goals among technicians.

PMID- 8133924
TI  - Shortage of renal care professionals impacting quality of care.

PMID- 8133925
TI  - Forward thinking: utilization of technicians in peritoneal dialysis units.

PMID- 8133926
TI  - Technicians in peritoneal dialysis not a new idea.

PMID- 8133927
TI  - Improving the accuracy of diagnosing patients with ESRD.

PMID- 8133928
TI  - A new technique for determining recirculation in the ESRD patient.

PMID- 8133929
TI  - Price controls in the pharmaceutical industry could hurt medical education.

PMID- 8133930
TI  - Accountability: a cost-saving approach to quality health care.

PMID- 8133931
TI  - NRAA to concentrate on state legislation, quality of care for 1994.

PMID- 8133932
TI  - Understanding the dangers of fluoride during dialysis.

PMID- 8133933
TI  - Outcomes research and health care reform: opportunities for nurses.

PMID- 8133934
TI  - The relationship of health care experience to satisfactory relocation in long
      term care.
AB  - Nurses and other health care workers have observed and documented in the
      literature a change or deterioration in the physical and mental health of
      residents pursuant to relocation to a long-term care facility. This study was
      designed to look at the influence on successful relocation of a possible
      contributing factor, previous experience in health care. Using random selection
      from 100 residents from four Louisiana nursing homes, 50 long-term care residents
      were asked to participate in a structured interview. Quality and quantity of
      previous health care as well as factors present in the previous health care
      experience were examined with respect to successful relocation. Analyses by ANOVA
      and Pearson product moment correlation were performed. No significance was found
      between the independent and the dependent variable, except for one item on the
      questionnaire, "How do you rate your overall medical care?" This response was
      found to have a significant relationship with the score of the Life Satisfaction
      Index. A significant relationship was also found between religion and room change
      and between degree of perceived internal control and Life Satisfaction Index
      score.

PMID- 8133935
TI  - Allocation of scare resources as perceived by master's students in nursing
      service administration.

PMID- 8133936
TI  - A new strategic planning model for a community-based nursing services program.
AB  - Models provide a way of envisioning effective action within a process. This paper
      discusses the application of the Boswell-Hensley Strategic Planning Model in the
      development of a community-based nursing service program. While the concepts,
      processes, and examples represented in this model are aimed specifically at
      community-based nursing service, the model can be applied to other health care
      services. The Boswell-Hensley model works on the assumption that humans with
      kindred motivations can agree on mutual goals and form rewarding partnerships
      that in the long term will advance the collective interest.

PMID- 8133937
TI  - Medical records: promoting patient confidentiality.

PMID- 8133938
TI  - A strategy for decreasing anxiety of ICU transfer patients and their families.
AB  - With the growing number of clients transferred out of the intensive care units
      (ICUs) following increasingly shorter stays, time constraints have become a
      barrier to effective teaching. Written information that is readily available to
      clients helps resolve this problem. A pamphlet (in Spanish and English) was
      developed to ease the move for patients, families, and critical care and medical
      nurses from a medical ICU (MICU) to a general floor.

PMID- 8133939
TI  - An interdisciplinary approach to improving the quality of life for nursing home
      residents.
AB  - As people live longer, there is a greater concern about not only the increasing
      life span but the quality of life (QOL) in later years. The purpose of this
      project was to design and pilot test interdisciplinary interventions with nursing
      home residents and to improve their QOL. This article focuses on
      interdisciplinary interventions that evolved during the project. While this
      program was an additional responsibility for members of the team, many benefits
      were realized and range from increased resident satisfaction to cost savings, to
      the recruitment of staff. An interdisciplinary team approach can be an effective
      means to improve quality of life for residents of nursing homes.

PMID- 8133940
TI  - Capital punishment and professional nursing.
AB  - This paper examines the issue of capital punishment and whether a professional
      nurse has the right to choose to participate in it. Capital punishment is an
      extremely emotional ethical issue, and there is abundant literature to support
      both viewpoints. Professional nursing upholds values and special moral
      obligations, as expressed in its code. The American Nurses Association Code for
      Nurses guides conduct in carrying out nursing responsibilities consistent with
      the ethical obligations of the profession.

PMID- 8133941
TI  - Resolving authorship.

PMID- 8133942
TI  - [Rachitis in premature children fed with breast milk].

PMID- 8133943
TI  - [Atherosclerosis partly due to local vasculitis].

PMID- 8133944
TI  - [Triglycerides and atherosclerosis; treatment of hypertriglyceridemia].

PMID- 8133945
TI  - [To treat or not to treat children with familial hypercholesterolemia].

PMID- 8133946
TI  - [Hyperhomocysteinemia as risk factor for premature atherosclerosis].

PMID- 8133947
TI  - [Poor results of treatment of echinococcosis with albendazole in 7 patients].
AB  - OBJECTIVE: To assess the effect of treatment of echinococcal disease with
      albendazole, a drug recently licensed in the Netherlands for this treatment.
      SETTING: The University Hospital Utrecht and the Wilhelmina Children's Hospital,
      Utrecht. DESIGN: Follow-up study. METHOD: Clinical symptoms, serology and size
      and morphology of cysts of all patients (n = 7) treated with albendazole with a
      therapeutical dose (10 mg/kg for adults and 6 mg/kg for children in two daily
      doses during three cycles of 28 days) were monitored for at least one year.
      RESULTS: Two patients improved, two patients did not show any change, and the
      condition of three patients deteriorated. CONCLUSION: The efficacy of albendazole
      treatment with this regimen for hydatid disease is disappointing. If patients are
      treated with albendazole, the total dose administered to adults should be more
      than 80 g.

PMID- 8133948
TI  - [Thyroid cancer in Southeastern Netherlands, 1970-1989: trends in incidence,
      treatment and survival].
AB  - OBJECTIVE: To describe the (changes in) incidence, treatment and prognosis of
      thyroid cancer (TC) in the period 1970-89 in the South-east of the Netherlands.
      SETTING: Eindhoven Cancer Registry, Comprehensive Cancer Centre South (I.K.Z.),
      Eindhoven. DESIGN: Retrospective. PATIENTS AND METHODS: Data were collected from
      al TC patients (ICD-O code 193 and non-Hodgkin lymphoma originating from the
      thyroid) diagnosed in the period 01.01.1970-31.12.1989. Histological, treatment
      and survival (on 01.07.1991) data were collected. The standardised incidence,
      prevalence, (relative) survival and mortality were calculated for men and women.
      RESULTS: The mean age of the 297 TC patients was 52 years; the male-female ratio
      was 1:2.3. 46% Of the TC patients had papillary TC, 35% follicular TC. The
      incidence of TC increased from 1.4 to 3.0/100,000/yr for females, the incidence
      remained unchanged for males (1,1/100,000/yr). The point prevalence (01.07.1991)
      was 25.6/100,000 for females and 8.2/100.000 for males. TC patients were treated
      in all hospitals in the region and were increasingly first seen bij an internist.
      There was a trend to more extensive surgical treatment and iodine-131 treatment
      in differentiated TC. For all TC patients the crude 10-year survival rate was
      61%, the relative 10-year survival rate was 74%. Survival was related with sex,
      age and histological type. Mortality from TC remained very low. CONCLUSIONS: The
      incidence and prognosis of TC were similar to the surrounding countries. In
      general the recommendations from the consensus meetings for treatment of TC in
      1985 and 1987 appear to be followed.

PMID- 8133949
TI  - [Vitamin B12 deficiency due to abnormal eating habits].
AB  - Vitamin B12 deficiency is an uncommon disorder in a prosperous western country.
      In two children a nutritional vitamin B12 deficiency was observed. The first was
      a 2-year-old girl with neurodevelopmental regression and macrocytic anaemia, a
      result of a combination of a maternal vitamin B12 deficiency and inadequate
      feeding after birth. The second patient was a 14-year-old adipose girl with
      severe polyneuropathy and mild macrocytic anaemia as a result of a nutritional
      vitamin B12 deficiency. In her case the deficiency resulted from a bizarre
      feeding pattern. She turned out to be the victim of child abuse. It is concluded
      that even in a prosperous western country like the Netherlands vitamin B12
      deficiency in children can develop as a result of an inadequate feeding pattern.
      It can lead not only to macrocytic anaemia but also to severe neurological
      abnormalities.

PMID- 8133950
TI  - [Multiple value of sumatriptan above that of ergot alkaloids still not proven].

PMID- 8133951
TI  - [Multiple value of sumatriptan above that of ergot alkaloids still not proven].

PMID- 8133952
TI  - [Ruptured aneurysm of the abdominal aorta with a clinically misleading picture].

PMID- 8133953
TI  - [Anaphylactic reactions following insect bites: clinical aspects, course and
      treatment].

PMID- 8133954
TI  - [Partial instead of complete splenectomy in children for pathological staging of
      Hodgkin's disease].

PMID- 8133955
TI  - [Use of alternative treatment methods].

PMID- 8133956
TI  - ['The pill' in the drugstore: unfavorable for safe use of drugs].

PMID- 8133957
TI  - [Additional treatment of bacterial meningitis using corticosteroids still
      insufficiently supported].

PMID- 8133958
TI  - [Hemolytic disease in a neonate caused by rare maternal anti-erythrocyte
      antibodies and exchange transfusion with earlier frozen maternal blood].

PMID- 8133959
TI  - [Transplantation of the sympathetic ganglion into the brain].

PMID- 8133960
TI  - [Clinical analysis of the fatal cases of adult malignant gliomas after aggressive
      treatment].
AB  - Six patients operated on for supratentorial malignant astrocytomas and seven
      patients operated on for glioblastoma multiforme were analyzed to evaluate the
      effect of aggressive surgical resection on the length of survival and causes of
      death. Early postoperative contrast enhanced CT scan was used to assess the
      extent of surgical resection. A gross total resection was considered to have been
      accomplished when there was no evidence of any residual enhanced mass. When 10%
      or less of the preoperative enhanced mass remained, the resection was classified
      as a subtotal resection. Subsequent follow-up CT scan showed that a gross total
      resection was accomplished in nine patients, and a subtotal resection was
      attained in four patients. The patients' ages ranged from 40 to 78 years (mean,
      59 years). The median survival after the first aggressive surgical resection was
      18.0 months in patients with malignant astrocytoma and 13.6 months in those with
      glioblastoma multiforme. The median duration between first operation and
      recurrence of tumor was 8.8 months in patients with malignant astrocytoma and
      11.5 months in those with glioblastoma multiforme. A second aggressive surgical
      resection for recurrent malignant astrocytoma or glioblastoma multiforme was
      carried out in four patients (40%) of the evaluated ten patients. The median
      survival of these patients after reoperation was 8.25 months. Accordingly,
      aggressive surgical resection of malignant astrocytoma and glioblastoma
      multiforme is correlated with longer survival and is advocated in the treatment
      of recurrent tumors. Leptomeningeal dissemination was diagnosed in nine patients
      (90%) of evaluated ten patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133961
TI  - [Surgical treatment of arteriovenous malformations in the brain stem].
AB  - The authors report the surgical removal of four arteriovenous malformations
      (AVM's) in the brain stem causing hemorrhage. These included two intra-axial and
      two extra-axial AVM's. Three of the four were situated at the pons, and the
      remaining one in the posterior medullary velum. Complete surgical removal was
      obtained in the two extra-axial cases and in one of the intra-axial cases. The
      patient in whom complete removal was not obtained received partial embolization
      therapy with the remaining feeder being coagulated surgically. No patient was
      made permanently worse after surgery. One patient, in a comatose state on
      admission, died, while the remaining three patients showed useful recovery. These
      data indicate that surgical therapy with or without endovascular surgery appears
      to be possible for some AVM's and can be performed at an acceptable risk.

PMID- 8133962
TI  - [Sequential changes of the cerebral blood flow in hypertensive putaminal
      hemorrhages].
AB  - PURPOSE: This study was designed to investigate the sequential changes of the CBF
      in hypertensive putaminal hemorrhage and to attempt to correlate these data with
      the treatment and ADL. METHOD: The CBF of 28 patients, aged from 39-70 years-old
      without any past history of cerebral insult, was measured sequentially from the
      acute stage by the xenon-enhanced CT method. Regarding treatment, 11 were treated
      conservatively, while 11 underwent stereotactic aspiration and the remaining 6
      had an evacuation of the hematoma by craniotomy. RESULTS AND CONCLUSION: 1. The
      CBF of the hemisphere, thalamus and cortex progressively decreased until 16 weeks
      after onset, and then recovered gradually. However, the reduction in the CBF
      continued until reaching the chronic stage at a 20-40% reduction level on both
      sides. 2. A negative correlation between the CBF and the hematoma volume was
      noted and in hematoma over 15ml in volume, the CBF always decreased below a level
      of 30ml/100g/min. 3. There was no correlation between the CBF and the hematoma
      extension to the internal capsule. 4. There was a significant correlation between
      the CBF and ADL. 5. A hematoma measuring less than 15ml should be treated
      conservatively. 6. In hematoma measuring more than 15ml, stereotactic aspiration
      proved to be more effective than other therapies not only for the recovery of the
      CBF but also for ADL.

PMID- 8133963
TI  - [Dilated pericerebellar fluid space in patients with chronic subdural hematoma].
AB  - It is not uncommon to observe the dilation of the pericerebellar fluid space
      (PCFS) on CT in patients with chronic subdural hematoma (CSDH). CT scans of 92
      patients with CSDH proven by surgery were reviewed with respect to the dilatation
      of PCFS and we evaluated the incidence of dilated PCFS and the relationship
      between PCFS and other factors. There were 68 males and 24 females. Patients
      ranged in age from 20 to 90 years (mean 65.2 years). Another 50 patients without
      CSDH were also reviewed as a control group. A new PCFS grading based on the CT
      findings was proposed, divided into 3 grades as follows. In grade 0, no PCFS
      could be seen on CT scans. In grade 1, PCFS could be detected along the posterior
      aspect of the petrous pyramid, and in grade 2, PCFS could be seen not only along
      the posterior aspect of the petrous pyramid but also under the tentorium
      cerebelli. The dilation of PCFS was seen in 78 patients (84.8%) out of the 92
      cases. In 50 patients without CSDH (control group), the dilatation of PCFS was
      noted only in 6 (12%). The dilatation of PCFS was almost always seen on the same
      side as the CSDH. Among many factors, the significant factor was the degree of
      the midline shift, the bigger the midline shift caused by CSDH, the larger was
      the dilated PCFS. Although the mechanism of the dilated PCFS in patients with
      CSDH is not clear, it is postulated that the mechanism is caused by CSF flow
      disturbance, compression or adhesion of the subarachnoid space due to
      CSDH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133964
TI  - [Utility of selective cerebral angiography through the transbrachial route].
AB  - Selective cerebral angiography through the transbrachial route was performed in a
      total of 102 patients including those at the acute phase (24 with subarachnoid
      hemorrhage, 10 with malformation of cerebral vessels, 7 with brain tumor, 49 with
      ischemic cerebrovascular disease, and 12 with other cerebrovascular
      abnormalities) from May, 1990 to March 1993. The patients were from 14 to 82
      years of age, and 20% of them were 70 years or older (74.7 +/- 3.29 years). A 5
      Fr. introducer catheter (Radifocus Introducer Kit A, Terumo Corp., Tokyo) was
      placed in the brachial artery at the bend in the right arm. A Judkins type-4cm
      right coronary catheter (C.R. Bard, Inc., Massachusetts) was selectively inserted
      into the common carotid artery and vertebral artery through this 5 Fr. introducer
      catheter, and angiography was performed. Three cases of unsuccessful puncture of
      the brachial artery were excluded, and the remaining 99 cases were included in
      the analysis. Transbrachial selective cerebral angiography was performed in 58,
      34, 88, and 90% of the total number of cases, subjected to cerebral angiography
      in 1990, 1991, 1992, and 1993 respectively. Thus, this approach to the cerebral
      vessels has been used in the majority of the recent cases. The rate of success in
      terms of angiography (no. of occasions/no. of attempts * 100) was 99% (73/74) for
      r-CAG, 94% (52/55) for 1-CAG, 100% (41/41) for r-VAG, and 82% (9/11) for 1
      VAG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133965
TI  - [Empty sella as an intrasellar herniation of the third ventricle secondary to
      spontaneous degeneration of a prolactinoma].
AB  - A case of a large empty sella was reported, which was intrasellar herniation of
      the third ventricle associated with a prolactinoma. The patient was a 46-year-old
      female admitted due to consciousness disturbance with pyrexia and vomiting. She
      had amenorrhea, galactorrhea and sterility in her past history. On admission,
      physical and neurological examinations revealed severe dehydration, systemic
      edema, systemic hypotension, nuchal rigidity, papilloedema and goiter. A spinal
      tap was performed and revealed an increase in CSF pressure. Laboratory data
      indicated CSF lymphocytosis, an increase in CSF protein content, high titers of
      serum microsome test, a low concentration of anterior pituitary hormones in serum
      except for PRL, and an unusually high concentration of PRL in serum and CSF (4680
      and 222ng/ml, respectively). Plain films of the skull showed destructive
      enlargement of the sella turcica. The patient was diagnosed as having non
      bacterial meningitis, chronic thyroiditis and a prolactinoma with hypopituitarism
      and was then admitted to our department. Except for amenorrhea she was
      asymptomatic under the administration of levothyroxine, hydrocortisone and
      bromocriptine. CT scan, MRI, pneumoencephalography and CT cisternography as
      further examinations disclosed the intrasellar herniation of cisterns and the
      third ventricle, which were surrounded by an intrasellar parenchymal layer. This
      layer was thought to be still viable prolactinoma tissue. We supposed the third
      ventricle entered the enlarged sellar cavity following the spontaneous
      degeneration of the large prolactinoma. Although we could find some documented
      reports of similar cases, the complete herniation of the third ventricle
      secondary to degeneration of an adenoma might be rare.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8133966
TI  - [A case of acute subdural hematoma due to dural metastasis from malignant pleural
      mesothelioma].
AB  - A rare case of acute subdural hematoma due to dural metastasis from malignant
      pleural mesothelioma is reported. A 65-year-old man was brought to a nearby
      hospital complaining of lumbago. He suddenly complained of headache on the third
      hospital day and fell into a deep coma within a short while. Computed tomography
      showed a crescent shaped high density area in the right fronto-temporo-parietal
      region with midline shift to the left side. He was admitted as an emergency case
      to our clinic on April 24, 1989. Under the diagnosis of acute spontaneous
      subdural hematoma, emergency operation was performed. Nests of malignant
      sarcomatous cells were found in the clot obtained during the procedure, but the
      origin of the tumoral cells could not be identified. The patient failed to
      recover from the comatose state and died with pancytopenia on the 17th hospital
      day. General autopsy showed wide-spread malignant pleural mesothelioma with
      metastases to the lung, liver and bone marrow. Examination of the head revealed
      dural metastatic tumor and a subdural hematoma over the left hemisphere.
      Histopathology showed that many tumor cell nests were found only within the
      dilated veins of the dura. There, acute subdural hematoma was assumed to have
      developed suddenly and there was massive bleeding from the capillaries of the
      inner vascular layer of the dura. The relevant literature about intracranial
      metastasis of malignant pleural mesothelioma was reviewed, and the mechanism of
      subdural hematoma due to dural metastasis from malignant tumor was discussed.

PMID- 8133967
TI  - [Traumatic middle cerebral artery occlusion].
AB  - A 16-year-old boy developed motor aphasia and right hemiplegia after head trauma
      caused during Rugby football club activity. About 2 hours after trauma, these
      neurological deficits improved dramatically. CT scan on admission revealed no
      abnormal finding. But, on the next day, CT scan revealed an irregular low density
      area at the left basal ganglia. Cerebral angiography showed a slight narrowing at
      the left carotid siphon, severe stenosis at M1 portion of the left middle
      cerebral artery with vasospasm of its distal branches and occlusion of the left
      anterior temporal artery. The extracranial portion of the left internal carotid
      artery was intact. Clinically, the patient recovered from the right hemiparesis
      almost fully and was discharged after 1 month with mild dyscalculia. Three months
      later, follow-up angiography disclosed stenosis of the left M1 portion but the
      narrowing of the carotid siphon and vasospasm of the peripheral branches of the
      middle cerebral artery had been normalized, and the anterior temporal artery was
      recanalized. The pathogenesis of the occlusion is classified into 4 causes, 1)
      embolism from internal carotid artery, 2) vasospasm, 3) thrombus formation, 4)
      dissection. However, the demonstration of this by angiography is difficult. In
      our case, the injury of the intracranial portion of the internal carotid artery,
      which caused the intimal injury, spasm or thrombus formation, might have happened
      and resulted in embolisation and recanalization of the middle cerebral artery.

PMID- 8133968
TI  - [Two cases of traumatic intracerebral pneumocephalus].
AB  - Two cases of traumatic intracerebral pneumocephalus, a rare complication of head
      trauma, are presented. Case 1: A 14-year-old boy had a strong concussion in his
      forehead due to a motorbike accident. Slightly obtunded on admission showing GCS
      10, he became conscious in several days. Head CT performed after 17 days showed a
      round air image in the right frontal lobe which kept increasing in size
      thereafter. Bilateral frontal craniotomy was performed 31 days after the injury.
      A craniodural defect with a herniated brain was found in the superior wall of the
      posterior ethmoid sinus and repaired. Case 2: A 55-year-old man received a left
      forehead concussion when his motorbike ran into a car from behind. Although he
      had been conscious ever since admission, head CT after 15 days showed a round air
      image in the left frontal lobe. MRI demonstrated the air to be located in the
      cerebral parenchyma distinctly and the brain to have herniated into the frontal
      sinus. As the air showed a tendency to increase in volume and mild psychic and
      memory disturbances appeared, bilateral frontal craniotomy was performed 34 days
      after the injury. A craniodural defect with a herniated brain was detected in the
      posterior wall of the frontal sinus and repaired. These two patients showed a
      small amount of cerebrospinal fluid (CSF) rhinorrhea before the operation.
      Following the surgical repair, no recurrence of pneumocephalus and CSF rhinorrhea
      has been seen in either case. Intracerebral pneumocephalus secondary to closed
      head trauma was thought to have been due to herniation of contused brain into a
      craniodural defect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133969
TI  - [Percutaneous transluminal angioplasty for progressing stroke caused by severe
      basilar artery stenosis: case report].
AB  - We encountered one case of progressing stroke caused by severe basilar artery
      stenosis. The patient was treated with emergent percutaneous transluminal
      angioplasty (PTA) with satisfactory results. A 54 year-old woman was admitted 15
      minutes after the sudden onset of rt. hemiparesis, rt. hemidysesthesia,
      dysarthria and consciousness disturbance. CT scan on admission showed no abnormal
      findings. The consciousness level of the patient deteriorated rapidly from JCS 1
      to JCS 20 within 30 minutes from the ictus. An emergent angiogram revealed severe
      basilar artery stenosis at its middle portion and poorly developed collateral
      circulation. One hour after the stroke occurred, PTA was performed. Using a 3mm
      diameter balloon catheter, we introduced the balloon into the stenotic lesion and
      inflated it 6 times from 4 atm to 8 atm pressure. The patient recovered
      immediately on the operating table improving from JCS 20 to JCS 1. Rt.
      hemiparesis also improved. Follow-up MRI showed a small area of ischemic change
      in the brain stem, but no large infarction appeared. The patient was discharged
      with no neurosurgical deficits after 30 days of PTA. PTA for basilar artery
      stenosis is still a controversial subject. One reason is the risk of basilar
      artery perforating branches occlusion by balloon catheter and the other is the
      difficulty of introducing a flexible balloon catheter into the basilar artery
      beyond the acute angulation of the vertebral artery. If those two problems were
      solved, PTA would be the first-choice therapy for basilar artery stenosis in both
      acute and chronic stages.

PMID- 8133970
TI  - [A case of suprasellar intradural chordoma].
AB  - An extraosseous and intradural chordoma of the suprasellar region is described in
      a 54-year-old male who presented himself with left homonymous hemianopia.
      Computed tomography showed an isodensity tumor containing a cyst in the
      suprasellar region. Magnetic resonance images demonstrated the tumor as an
      isointense mass with heterogeneous enhancement after intravenous administration
      of a contrast agent, and as a high signal intensity mass on T2-weighted images.
      The associated cyst was also clearly demonstrated. The tumor was diagnosed
      preoperatively as a craniopharyngioma and was resected using the frontobasal
      interhemispheric approach. However, the resected tumor had the typical
      histological and immunohistochemical characteristics of chordoma. Only ten cases
      of totally extraosseous and intradural chordoma have been reported. The
      histogenetic background of this tumor is also discussed in this paper.

PMID- 8133971
TI  - [A case of convexity arachnoid cyst associated with chronic subdural hematoma and
      intracystic hemorrhage].
AB  - Arachnoid cysts account for about 1% of all intracranial tumors, in which about
      50% arise from the middle cranial fossa, and rarely occur at the cerebral
      convexity. They sometimes are associated with chronic subdural hematoma (CSDH)
      but the exact mechanism of their development is still unclear. A 15-year-old boy
      was admitted to our hospital with an arachnoid cyst at the right frontal
      convexity. When he experienced recurrent generalized seizure, CT and MRI revealed
      CSDH localized at the surface of the arachnoid cyst. Radical operation for the
      cyst with CSDH was successfully performed. As far as we know, it is rare that
      CSDH and hematoma are colocalized over an arachnoid cyst at the cerebral
      convexity. In this report, the operative findings of this patient and possible
      mechanism of CSDH formation were reported.

PMID- 8133972
TI  - [A ruptured peripheral, superior cerebellar artery aneurysm: a case report and a
      review of the literature as to surgical approaches].
AB  - The authors described the case of a normotensive 40-year-old female with severe
      headache and vomiting. Neurological findings on admission to our hospital
      revealed no deficits, but plain CT findings indicated subarachnoid hemorrhage in
      the ambient, supracerebellar, quadrigeminal, and right lateral pontine cisterns.
      Left vertebral angiograms made through a transfemoral catheter revealed a
      saccular aneurysm (6 x 4mm) arising from the medical hemispheric branch of the
      right superior cerebellar artery (SCA). On the 34th day after onset of her
      symptoms, the aneurysm was successfully clipped by using an infratentorial
      supracerebellar approach. She was discharged with no deficits. Based on our
      experience and a review of the literature, a peripheral SCA aneurysm is best
      clipped by using one of the following surgical approaches: (1) a subtemporal
      transtentorial approach for an aneurysm arising from the anterior or lateral
      pontomesencephalic segment, (2) a subtemporal or occipital transtentorial
      approach for an aneurysm arising from the cerebellomesencephalic segment or the
      proximal cortical branch, or (3) an infratentorial supracerebellar approach for
      an aneurysm arising from the distal cortical branch.

PMID- 8133973
TI  - [Recurrent meningioma with malignant transformation: a case which changed from
      meningothelial type to papillary type].
AB  - We report here a case with meningioma showing malignant transformation in its
      course of multiple recurrences. A 59-year-old woman developed a right-sided
      hemiparesis in June, 1982 and CT scan disclosed a parasagittal well-enhanced
      mass. The tumor was subtotally removed (Simpson grade III) by an operation in
      September, 1982. Histological findings of the tumor were consistent with a
      meningothelial meningioma but showed no malignant features, such as high
      cellularity, necrotic foci, high mitotic rate, or nuclear pleomorphism. However,
      the tumor did invade the underlying cerebral cortex. In August, 1986, a recurrent
      tumor was detected by CT scan and was removed (Simpson grade III). The tumor
      tissue at the second operation showed the same histological features as the first
      specimen. In September, 1990, the patient developed multiple intracranial
      recurrences. There were three tumor nodules, all of which were removed.
      Histologically, significant histological differences between the second and the
      third operative specimens were found. In the last tumor tissue, one nodule showed
      a papillary pattern. In the other tumor nodules, each tumor cell had proliferated
      separately instead of adhering to other tumor cells to form a syncytium. This
      histological pattern was consistent with an epithelial meningioma described by
      Cushing and Eisenhardt in 1938. The papillary portion of the tumor was stained
      with monoclonal antibody Ki-67 in frozen section. The labelling index was 9.7%,
      which was as high as malignant meningioma. Electron microscopic examination of
      the papillary portion of the tumor showed that the tumor cells had irregular
      nuclei, interdigitations between the adjacent plasma membranes and a few ill
      developed desmosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133974
TI  - Neuroradiological (MRI) abnormalities in phenylketonuric subjects: clinical and
      biochemical correlations.
AB  - A clinical, biochemical and neuroradiological (MRI) study was performed in 22
      hyperphenylalaninemic patients detected by neonatal screening and early treated
      (Group A; 5-23 years old, 13 females and 9 males) and in 5 late detected,
      symptomatic subjects (Group B; 9-23 years old, 3 females and 2 males). The
      screening subjects were clustered in a Group A1 (10 on diet patients), and a
      Group A2 (12 after end of diet patients). On MRI examination (1.5-T magnet, SE T1
      weighted 530/22/2, T2-weighted 2400/15-90/1 sequences, SL 6 mm, gap 1.8) a
      symmetrical increase of the T2-weighted signal in the periventricular white
      matter was found in all patients. The periatrial white matter was always
      involved, the occipital region was affected in 22 cases, the frontal region in
      16. Concomitant signal decrease on the T1-weighted sequences in the same areas
      with the highest signal intensity on the T2-weighted scans was found in 7
      patients (in 3 out of 12 Group A2 and in 4 out of 5 Group B patients). In 6 Group
      A and in 3 Group B subjects a variable degree of cortical and subcortical atrophy
      was detected. A significantly positive correlation was found between white matter
      involvement and the degree of recent exposition to high PHE values. This
      correlation was also confirmed when only Group A was examined. Moreover, a
      significant difference in neuroradiological involvement was found between Group
      A1 and Group A2 subjects, but not between Group A2 and Group B subjects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8133975
TI  - Somatosensory evoked potentials and cognitive sequelae in children with closed
      head-injury.
AB  - In search of a prognostic indicator for residual cognitive function loss in
      children after closed head-injury, the somatosensory evoked potential P300 has
      been studied in a prospective follow-up study of 17 patients with mild and
      moderately severe head-injuries. The P300 response was measured in the acute
      phase after patients regained consciousness. In addition the duration of coma and
      of post-traumatic amnesia were recorded. An age-matched control group of 20
      healthy children supplied age-related normative evoked potential data. During a
      two-years follow-up period the presence of residual disorders in various
      faculties was evaluated at fixed time intervals after discharge. Correlation
      analyses revealed that, where the duration of coma and of post-traumatic amnesia
      qualify as general predictors of sequelae, the long-latency somatosensory evoked
      potential P300 correlated specifically with long-term deficits in the field of
      school performance.

PMID- 8133976
TI  - Ondine's curse: a discussion of five cases.
AB  - Five cases of central congenital hypoventilation, Ondine's curse, were studied.
      The diagnostic criteria were: lack of respiratory autonomy during sleep, abnormal
      CO2 test results and abnormal respiratory monitoring results during sleep. This
      hypoventilation induced chronic complications, such as a pulmonary arterial
      hypertension and psychomotor and/or growth retardation. The other conditions
      frequently associated with Ondine's curse were: brainstem disturbances,
      Hirschsprung disease and neuroblastoma. Since other brainstem dysfunctions are
      sometimes associated with hypoventilation and because complications can arise,
      these children routinely underwent complementary investigations. Treatment was
      symptomatic. Assisted mechanical ventilation was initiated as soon as possible
      and carefully monitored. The prognosis for these children has greatly improved
      and some of them lead a normal life with nightly assisted ventilation at home.

PMID- 8133977
TI  - Moebius syndrome: continuous tachypnea verified by a polygraphic study.
AB  - Four polygraphic recordings were obtained in three cases of Moebius syndrome. The
      cases were a 4-month-old girl (Case 1), a 4-year-old boy (Case 2), and a 5-year
      old girl (Case 3). The recordings revealed that in all three cases there was a
      lack of rapid eye movements to the lateral side, continuous low amplitude on chin
      EMG, and continuous tachypnea. In Case 3, polygrams were recorded at 2 and 5
      years of age, both records showing the same pattern of tachypnea. Arterial blood
      gas analysis (AGA), PH, PaCO2 and PaO2 were found to be within normal limits. It
      has been assumed that this syndrome includes brainstem dysplasia, according to
      the chief symptoms, and autopsy and auditory brainstem response (ABR) findings.
      ABR examination showed low amplitude of waves, a prolonged wave I-V interval, and
      the absence of wave V. It is known that there is a close relationship between
      this syndrome and respiratory disorders. But there have only been a few reports
      on respiratory disorders in this syndrome. It is strongly believed that
      continuous tachypnea is an important symptom of Moebius syndrome.

PMID- 8133978
TI  - Stimulus specificity of P300.
AB  - P300 recordings are valuable and noninvasive neurophysiological research tool to
      gain further insight into higher cerebral function. Due to methodological and
      technological restrictions the clinical applicability of these investigations for
      neuropediatric purposes was limited. To enhance the usefulness of this phenomenon
      for clinical practice in neuropediatrics a convenient, painless and short-lasting
      procedure was imperative. For this purpose we developed a visual priming
      technique to average P300 components in children. To estimate the sensitivity of
      this procedure two classes of modality-different stimuli were used to prime
      visual P300 recordings. Forty children were examined, while P300 averagings for
      target and related nontarget events were recorded during spatial and verbal
      stimulation. Topographical brain electrical activities of match/mismatch events
      were compared by complex statistical MANOVA methods for each period to compute
      modality-specific components within the surface recorded P300 waveforms. Latency
      statistics were correlated. Our data indicate significant differences between
      various topographical P300 distributions, showing a close relationship between
      the experimental priming period and the activity of distinct cortical regions
      involved in spatial-imagination and language-processing.

PMID- 8133979
TI  - Lamotrigine in resistant childhood epilepsy.
AB  - Fourteen children (6 M, 8 F) suffering from refractory epilepsy received LTG as
      add-on therapy. LTG was administered twice daily at dosages increasing up to 2
      mg/kg/day (for patients taking VPA) or to 10 mg/kg/day for patients taking AEDs
      that induce hepatic metabolism. The drug was withdrawn for side effects in 3
      cases (rash: two cases, hirsutism: one), because of increased seizure frequency
      in 2 cases and because of unchanged seizure frequency in one. One patient died
      from acute respiratory failure, after repeated respiratory tract infections. A
      decrease in seizure frequency after one year of treatment with LTG was observed
      in 6 of the 7 patients who completed the study. The median total seizure
      frequency decreased from 10.7 +/- 7.3 to 3.8 +/- 4.6 seizures per day. At the end
      of the study, seizure frequency had decreased by more than 50% in 2 patients, by
      more than 75% in 2 patients, and 2 patients were seizure-free; in the remaining
      patient seizure frequency was unchanged. The best results were obtained with
      plasma LTG concentrations ranging from 0.5 to 5.4 micrograms/ml; no further
      improvement was observed at higher LTG concentrations.

PMID- 8133980
TI  - Kohlschutter syndrome: syndrome of epilepsy--dementia--amelogenesis imperfecta.

PMID- 8133981
TI  - Lamotrigine in Rett syndrome.
AB  - An elevated CSF glutamate level has recently been reported in Rett syndrome.
      Because the anticonvulsant effect of Lamotrigine is probably due to inhibition of
      glutamate release, this drug was given as an add-on drug to 4 girls with Rett
      syndrome. All patients responded with a seizure reduction of 50% or more and an
      improved well-being. A controlled study at the early stages of the syndrome could
      be interesting.

PMID- 8133982
TI  - Familial unilateral and bilateral occipital calcifications and epilepsy.
AB  - No familial cases of epilepsy associated with bilateral occipital calcifications
      (EBOC) have been reported so far. This paper describes the clinical,
      electrophysiological and radiological study of two sisters affected by partial
      epilepsy, one with unilateral and the other with bilateral occipital
      calcifications. Celiac disease was excluded in both patients, even though they
      presented the same HLA pattern usually found in coeliac subjects.

PMID- 8133983
TI  - Blind, deaf and mute after a status epilepticus caused by hyperpyrexia from
      shigellosis--a case report with a four-year follow-up.
AB  - A nearly four-year-old boy awoke blind, deaf and mute from a coma of five days
      duration after a status epilepticus caused by hyperpyrexia from shigellosis. The
      authors give a detailed report of the recovery. Visual and auditory functions
      recovered within six months after the onset but expressive language difficulties
      remained. Following a discussion of the underlying mechanisms producing the
      cerebral damage, the hypothesis of a type of "disconnection syndrome" is put
      forward to explain the persisting language deficit.

PMID- 8133984
TI  - Acute fatal parainfectious cerebellar swelling in two children. A rare or an
      overlooked situation?
AB  - We report 2 previously healthy children who developed sudden unexpected
      respiratory arrest and brain death, during a presumed Epstein-Barr meningitis in
      one case and a multisystemic infection of unknown etiology in the other. Diffuse
      swelling of the cerebellum with upward transtentorial and downward tonsillar
      herniation, shown by brain CT-scan and MRI obtained after the acute event, was
      the most probable cause of death. Review of CT images performed before or at the
      onset of deterioration already showed discrete signs of early upward herniation
      of the cerebellar vermis that were initially overlooked. At autopsy in the first
      case, an acute lymphomonocytic meningoencephalitis with predominant involvement
      of the cerebellum was observed. Few similar cases were found in the literature,
      indicating that acute cerebellar swelling is either a very rare or an
      unrecognized, possibly preventable cause of death in acute inflammatory or non
      inflammatory encephalopathies in children.

PMID- 8133985
TI  - Hemodynamic parameters in patients with acute cervical cord trauma: description,
      intervention, and prediction of outcome.
AB  - The cardiovascular response of the patient with acute spinal cord injury (SCI) is
      known to be altered secondary to the cord injury. Our current protocol of
      managing the acute phase of patients with SCI includes invasive hemodynamic
      monitoring (with arterial line and Swan-Ganz catheter) and support with fluids
      and dopamine and/or dobutamine, titrated to maintain a hemodynamic profile with
      adequate cardiac output (to be determined by oxygen consumption and delivery) and
      a mean blood pressure of > 90 mm Hg. We feel that this protocol provides two
      benefits: 1) maintaining the mean blood pressure improves the morbidity of these
      patients by deterring ischemia and accompanying secondary insults; 2) aggressive
      monitoring and hemodynamic intervention help stabilize the hemodynamic status of
      these patients and make it possible to consider early surgery in selected cases.
      Our hypothesis is that the pulmonary vascular bed is more sensitive to the
      sympathectomized effect of acute complete cervical SCI. We analyzed the
      demographic, neurologic, and hemodynamic data of 50 consecutive patients during
      their first week postinjury. All had signs of myelopathy; 31 (62%) were
      considered clinically complete. Of the 50 patients, 9 (18%) died, 20 did not
      improve functionally, and 21 improved. The mean heart rate (82.1 +/- 13.3), blood
      pressure (94.4 +/- 9.4), pulmonary artery pressure (22 +/- 5) and wedge (12.7 +/-
      3.4), cardiac index (4.5 +/- 0.9), systemic vascular resistance index (SVRI)
      (1637 +/- 399), pulmonary vascular resistance index (PVRI) (181 +/- 80), and
      oxygen transport (694 +/- 156) showed good response to the treatment. Because the
      measurements were obtained during treatment, they differ from the expected
      "classic sympathectomized" response, but they provide a database for further
      analysis of hemodynamic manipulation in SCI. An analysis of the hemodynamic
      parameters did not differentiate between complete and incomplete lesions or
      between patients with functional improvement. We determined, on the basis of the
      initial hemodynamic measurements, that no patient with a clinically complete
      motor deficit (Frankel Grade A+B) improved of the 10 who had measurements
      compatible with either: 1) PVRI < 100 with SVRI < 1200; or 2) PVRI < 115 with
      SVRI < 1300 or PVR/SVR ratio of < 0.08 when SVRI was < 1600. These patients could
      not have other measurements that showed low SVRI < 1350 with PVRI > 139. At odds
      with this unique group, 13 of 29 patients with the same clinical picture and
      without the above physiological criteria of severe hemodynamic deficit eventually
      improved (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8133986
TI  - Penetrating craniocerebral injury resultant from gunshot wounds: gang-related
      injury in children and adolescents.
AB  - We prospectively and retrospectively reviewed a series of 780 patients who
      presented to the University of Southern California/Los Angeles County Medical
      Center with a diagnosis of gunshot wound to the brain during an 8-year period. Of
      these, 105 were children ranging in age from 6 months to 17 years. Injuries were
      gang related in 76 (72%) children and adolescents. Stepwise linear regression
      analysis was used to formulate a predictive model of outcome in this population.
      Patient age (F = 10.92), sex (F = 9.32), occipital entry site (F = 8.17),
      bihemispheric injury (F = 8.50), and admission Glasgow Coma Scale (F = 69.91)
      were all found to correlate with outcome (P < 0.05). Significant differences
      between pediatric and adult populations were noted in transit time, entrance
      site, and age-related outcome. Occipital or assassination-type wounds were most
      common in children. In addition, a younger age was associated with poor outcome
      (P < 0.0001). We describe both the economic and racial trends in our population
      of patients in addition to weapon type and toxicological evaluation. The
      Department of Neurological Surgery is becoming directly involved in providing
      information to children at the junior high school level regarding gang activity
      and brain and spinal cord injury. In conjunction with the Community Youth Gang
      Services Organization and Think First Organization, we are attempting to
      integrate prevention through education and community mobilization. This is a plan
      aimed at informing and recovering the youth affected by gangs.

PMID- 8133988
TI  - Scientific and ethical concerns in neural fetal tissue transplantation.
AB  - This report presents a brief overview of the medical and ethical issues involved
      with the procurement, preparation, safety, efficacy, and subject protection of
      human fetal central nervous system tissue in the context of neural
      transplantation. The ethical perspectives from which to view the clinical use of
      fetal tissue include the following: 1) that fetal tissue from elective abortions
      is a surgical specimen; 2) that the use of such tissue involves fetal
      experimentation in which the fetus is a subject; and 3) that fetal tissue is
      considered as a cadaveric organ specimen, similar to other organs, but with
      special considerations compared with adult cadaveric tissue. The latter approach
      appears to be the most applicable and is parallel to the use of cadaveric organs
      and tissues after a declaration of brain death. Additional issues include the
      following: 1) the safety and quality of fetal tissue for implantation; 2) the
      hypothesis that "legitimization" and "redemption" (potentially positive effects
      of tissue donation in general) may lead to an increase in elective abortion
      rates; 3) the ethical issues of the validity and value of human experimentation
      involving neural grafting; and 4) the type of consent to be obtained and the
      appropriate timing. Elective abortions, however, probably will continue to be the
      primary source of fetal tissue for grafting for some time, until other tissue
      sources become available.

PMID- 8133989
TI  - An anatomicosurgical study of the temporal branch of the facial nerve.
AB  - The surgical anatomy of the temporal branch of the facial nerve was studied
      bilaterally in 10 embalmed cadaveric heads. Particular attention was paid to the
      relationships between the temporal branch, the galeal-fascial layers, and the fat
      pads of the temporal-zygomatic region. The temporal branch of the facial nerve
      pierces the parotidomasseteric fascia below the zygomatic arch. This branch
      travels first in the subcutaneous tissue and then, above the zygomatic arch, in
      the subgaleal space. The temporal branch divides into an anterior, a middle
      (frontal), and a posterior ramus soon after it pierces the parotid fascia. The
      course of the terminal twigs of the temporal branch of the facial nerve in the
      subgaleal space is extremely variable, with their location being at times
      posterior to the anterior one-fourth of the temporalis muscle. Occasionally, a
      twig for the frontalis muscle may run in between the two layers of the
      superficial temporal fascia. Because of these findings (anteroposterior
      variability of temporal branch twigs and recurrent intrafascial twig), Yasargil's
      interfascial dissection may at times fail. A combined frontotemporal
      scalp/superficial temporal fascia dissection is anatomically suited to preserve
      the temporal branch of the facial nerve.

PMID- 8133987
TI  - Magnetic resonance scans should replace biopsies for the diagnosis of diffuse
      brain stem gliomas: a report from the Children's Cancer Group.
AB  - Children's Cancer Group Protocol CCG-9882 was designed to determine the
      effectiveness of hyperfractionated radiation for the treatment of children and
      young adults with brain stem gliomas. The study opened for the accrual of
      patients on September 21, 1988, and was closed on June 30, 1991. The first 54
      children in the study were treated with irradiation doses of 100 cGy given twice
      daily to a total dosage of 7200 cGy. The next 66 children were treated with a
      similar daily regimens to a total of 7800 cGy. Tumors were diagnosed by clinical
      and radiographic criteria. Decisions about the need for surgery were left to the
      discretion of the treating neurosurgeon; tissue diagnosis did not alter the
      therapy in patients with diffuse infiltrating tumors. We reviewed the
      neuroradiology and neurosurgery reports as well as the pathological specimens of
      children entered on the study. By magnetic resonance (MR) imaging criteria,
      tumors involved the majority of the brain stem in 76% of cases; only three
      patients had tumors localized to the midbrain or medulla. Operations were
      performed on 56 of 120 patients (47%). Cerebrospinal fluid shunts were inserted
      in 27 (23%) of the children; insertion of a shunt was the only operation in 11,
      and a shunt was inserted in conjunction with a tumor operation in 16. Tumor
      operations were performed in 45 (38%) of the patients; 24 had stereotactic
      biopsies, and 21 had craniotomies. Of the 21 patients who had craniotomies, only
      biopsies were performed in 11; partial tumor resections were performed in 5
      patients and subtotal resection in 5.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8133990
TI  - Biomechanical evaluation of Caspar cervical screws: comparative stability under
      cyclical loading.
AB  - Anterior cervical instrumentation is used as an adjunct to bone fusion; however,
      definitive biomechanical data to support some applications and techniques are
      lacking. In the absence of supportive experimental data, posterior cortical
      penetration has been recommended with the Caspar system. Previously, we compared
      the axial pull-out strength of Caspar screws with and without posterior cortical
      penetration. This study compares the stability of unicortical versus bicortical
      screw penetration groups under cyclical loading simulating physiological flexion
      extension. Caspar screws were placed in human cadaveric vertebrae with or without
      posterior cortical purchase. Each screw was separately tested, simulating flexion
      extension to 200 cycles. Deformation time data allowed a direct comparison of
      screw "wobble" with and without posterior cortical purchase. The mean deformation
      differences between subcortical and bicortical groups were statistically
      significant and increased over time within both groups. Enhanced stability was
      noted with bicortical purchase throughout most of the examined range, becoming
      more pronounced over longer periods of cyclical loading. Significant (P < 0.05)
      increases in deformation over time were noted for both groups, suggesting
      potentially significant deterioration at the screw-bone interface, despite
      bicortical purchase. Such deterioration with repeated flexion-extension loading
      may be of concern in the use of Caspar plates in the presence of multicolumn
      instability.

PMID- 8133991
TI  - A review of brain retraction and recommendations for minimizing intraoperative
      brain injury.
AB  - Brain retraction is required for adequate exposure during many intracranial
      procedures. The incidence of contusion or infarction from overzealous brain
      retraction is probably 10% in cranial base procedures and 5% in intracranial
      aneurysm procedures. The literature on brain retraction injury is reviewed, with
      particular attention to the use of intermittent retraction. Intraoperative
      monitoring techniques--brain electrical activity, cerebral blood flow, and brain
      retraction pressure--are evaluated. Various intraoperative interventions-
      anesthetic agents, positioning, cerebrospinal fluid drainage, operative
      approaches involving bone resection or osteotomy, hyperventilation, induced
      hypotension, induced hypertension, mannitol, and nimodipine--are assessed with
      regard to their effects on brain retraction. Because brain retraction injury,
      like other forms of focal cerebral ischemia, is multifactorial in its origins, a
      multifaceted approach probably will be most advantageous in minimizing retraction
      injury. Recommendations for operative management of cases involving significant
      brain retraction are made. These recommendations optimize the following goals:
      anesthesia and metabolic depression, improvement in cerebral blood flow and
      calcium channel blockade, intraoperative monitoring, and operative exposure and
      retraction efficacy. Through a combination of judicious retraction, appropriate
      anesthetic and pharmacological management, and aggressive intraoperative
      monitoring, brain retraction should become a much less common source of morbidity
      in the future.

PMID- 8133992
TI  - Correlation of proto-oncogene expression and proliferation and meningiomas.
AB  - Proliferation and proto-oncogene expression in 19 meningiomas of typical and
      atypical histology were analyzed in an attempt to understand the mechanism of
      growth that characterizes the neoplastic process in these tumors. Proliferation
      was estimated as the proliferative index by the enumeration of S-phase cells in
      imprints of tumor tissue exposed to bromodeoxyuridine in vitro, and the gene
      expression of c-myc, c-fos, c-src, c-H-ras, N-myc, acidic and basic fibroblast
      growth factor, insulin-like growth factors I and II, platelet-derived growth
      factor-alpha, and epidermal growth factor was quantified by messenger ribonucleic
      acid dot-blot hybridization assay. Atypical and malignant tumors had
      significantly higher proliferative indexes than did their nonmalignant
      counterparts. Levels of c-myc and c-fos messenger ribonucleic acid were elevated
      more than fivefold in 72 and 78% of the tumors, respectively, relative to the
      lowest levels detected in the series. Levels of growth factor messenger
      ribonucleic acid were sporadically elevated; 37 to 44% of tumors had more than
      fivefold enhanced levels of acidic and basic fibroblast growth factor. Positive
      correlations between proliferation and proto-oncogene/growth factor expression
      were found for c-myc in atypical/malignant tumors and for epidermal growth factor
      in fibroblastic meningiomas. Deregulated expression of c-myc and c-fos common to
      both typical and atypical tumors suggests that these are early events in the
      meningioma tumor process that may disturb the control of cell differentiation and
      together with fibroblast growth factors are likely to endow the transformed cell
      with a selective growth advantage by reducing the requirement for exogenous
      mitogens and by providing a niche for the growth of the tumor clone. Positive
      correlation of c-myc levels with proliferation in atypical/malignant meningiomas
      implies that this is a feature of malignancy and indicates continued disruption
      of the negative regulation of proto-oncogene expression, perhaps by tumor
      suppressor gene losses, during the course of tumor progression.

PMID- 8133993
TI  - Kinetics of Photofrin II in perifocal brain edema.
AB  - Photodynamic therapy is under intense investigation as a possible adjuvant for
      the treatment of malignant tumors of the central nervous system. It relies on the
      fact that photosensitizers are selectively taken up or retained by malignant
      tissue. However, most brain tumors are accompanied by substantial vasogenic edema
      as a consequence of blood-brain barrier disruption within the tumor, leading to
      extravasation and propagation of plasma constituents into the surrounding brain
      tissue. Systemically administered photosensitizers may enter healthy tissue
      together with the edema fluid, possibly leading to sensitization of tissues
      outside the tumor. To test this hypothesis, vasogenic edema was induced by cold
      injury to the cortex in rats. The edema thus obtained is highly reproducible and
      very similar to tumor-associated edema. Just after injury induction, Photofrin II
      (PF-II), a commonly used photosensitizing agent, was administered at a dose of 5
      mg per kilogram of body weight along with fluorescein isothiocyanate (FITC)
      labeled albumin to mark edema advancement. After 1, 4, 12, or 24 hours, the
      brains were removed and frozen, and cryosections were studied with high
      sensitivity video fluorescence microscopy for edema extravasation within the
      lesion and propagation of PF-II into the surrounding gray matter. PF-II advanced
      with edema along the corpus callosum underlying the cortex to a distance of 5 mm
      from the lesion after 4 hours. With the exception of the lesion, PF-II
      fluorescence returned to baseline after 24 hours, indicating subsequent washout.
      Propagation was comparable to the spreading of FITC-marked albumin. The authors
      conclude that photosensitizers spread with edema, an observation that may be
      pertinent to a number of questions concerning photodynamic therapy of cerebral
      tumors.

PMID- 8133994
TI  - Experimental microsurgical repair of spinal roots.
AB  - Three different methods of nerve repair were evaluated in an experimental model
      of spinal root injury. In adult rats, dorsal L4 roots were cleanly severed and
      repaired by microsurgical techniques. Anastomosis was performed by direct end-to
      end suture, the arterial sleeve technique, or the interposition of a nerve graft.
      Results were evaluated 7, 10, and 14 weeks after surgery. Regeneration was
      studied by light and electron microscopy, showing a fair regenerative pattern in
      each group. The endoneurial connective response, including neovascularization,
      was more prominent after grafting. The artery sleeve technique is a very tedious
      procedure, and fibrosis around the artery and arachnoiditis were intense. A lack
      of continuity was found in 3 of 12 direct sutures. In conclusion, the best method
      for the reparation of nerve roots seems to be the interposition of a nerve graft.

PMID- 8133995
TI  - Embolization of a dural arteriovenous fistula of the ventral cervical spinal
      canal in a nine-year-old boy.
AB  - A 9-year-old patient presented with an acute left hemiparesis secondary to an
      intradural hemorrhage of the cervical spinal cord. Angiography revealed a dural
      arteriovenous (AV) fistula with multiple venous aneurysms fed by a radicular
      branch of the right vertebral artery. This AV fistula did not contribute blood
      flow to the cervical segment of the spinal cord, which was tested by an intra
      arterial injection of methohexital. Interruption of the fistula was possible by
      transluminal embolization with polyvinyl alcohol and silk. At a 6-month follow
      up, the patient was neurologically intact, and angiography demonstrated no AV
      fistula. This case illustrates an unusual presentation of a dural AV fistula.
      Dural AV fistulas are rare in the cervical region and extremely unusual in
      patients less than 20 years of age. The lesion proved to be amenable to
      transluminal embolization alone, without the need for surgery, with a dramatic
      resolution of the neurological deficit.

PMID- 8133996
TI  - Complete resection of a spinal meningioma extending from the foramen magnum to
      the second thoracic vertebral body via the anterior approach: case report.
AB  - The authors treated a patient with a huge, ventrally located spinal meningioma,
      extending from the foramen magnum to the second thoracic vertebral body.
      Vertebral body corpectomies were performed between the bottom of the second
      cervical vertebral body and the top of the first thoracic vertebral body, and the
      tumor was completely resected. Neurological symptoms and signs improved
      postoperatively.

PMID- 8133997
TI  - Intramedullary disseminated capillary hemangioma with localized spinal cord
      swelling: case report.
AB  - A case of intramedullary disseminated capillary hemangioma in the cervical spinal
      cord is presented. The patient showed progressive neurological deficits. Magnetic
      resonance imaging showed localized swelling of the spinal cord. This case was
      initially misdiagnosed at another institution as syringomyelia. Decompression of
      the posterior fossa and a syringo-subarachnoid shunt operation were performed.
      However, the operative findings in the authors' institution showed edematous
      tissue with no apparent neoplastic characteristics. Pathological findings
      revealed angiomatous nests consisting of small capillary-like vessels,
      telangiectatic vessels, and aggregated venules scattered in the edematous and
      partially necrotic spinal cord tissue. The edema and necrosis of the cervical
      cord were considered to have been caused by circulatory disturbances in the
      spinal cord parenchyma resulting from these vascular lesions.

PMID- 8133998
TI  - Carpal tunnel release complicated by acute gout.
AB  - We report a patient who suffered an acute attack of gout in the wrist after
      surgical release for carpal tunnel syndrome. The postoperative management of this
      patient and a brief review of this complication of carpal tunnel release are
      discussed.

PMID- 8133999
TI  - Iatrogenic cerebrospinal fluid fistula to the pleural cavity: case report and
      literature review.
AB  - The authors observed one case of an iatrogenic subarachnoid-pleural fistula
      secondary to the resection of an upper lobe carcinoma of the lung. The clinical
      presentation was characterized by a sudden deterioration of mental status and
      level of consciousness immediately after the removal of the thoracotomy chest
      tube. The diagnosis was substantiated by the demonstration of pneumocephalus by a
      computed tomographic scan of the head and by the identification of a left T5
      nerve root fistula by a postmyelographic computed tomographic scan. The excellent
      anatomical definition achieved by this modality emphasizes its usefulness in the
      identification and therapeutic management of these lesions. Operative treatment
      consisted of the suture ligature of the nerve root and a chest drain. The
      postoperative course was uneventful, and the outcome was excellent, with the only
      finding of sensory loss in the T5 nerve root territory. A review of the
      literature disclosed 11 similar cases, with some differences in the choice of the
      most appropriate diagnostic procedure and significant differences in the
      therapeutic options, which were related to the various mechanisms of injury.

PMID- 8134000
TI  - Visualization of the ostium of an arteriotomy in bypass surgery.
AB  - Visualization of the ostium of an arteriotomy by staining it blue with
      methylrosaniline chloride (pyoctaninum blue) in anastomotic bypass surgery for
      children with moyamoya disease is described. This technique enables surgeons to
      create an anastomosis more precisely and quickly. No adverse effects were
      observed.

PMID- 8134001
TI  - Quadriparesis after a shunting procedure in a case of cervical spinal neurinoma
      associated with hydrocephalus: case report.

PMID- 8134002
TI  - Stereotactic versus stereotaxic.

PMID- 8134003
TI  - Stereotactic radiosurgery: at the threshold or the crossroads?

PMID- 8134004
TI  - Lumboperitoneal shunting: a retrospective study in the pediatric population.

PMID- 8134005
TI  - Life-threatening reactions to propofol.

PMID- 8134006
TI  - Anterior tibial compartment syndrome as a positioning complication of the prone
      sitting position for lumbar surgery.

PMID- 8134007
TI  - Civilian gunshot wounds to the head.

PMID- 8134008
TI  - Atypical and malignant meningiomas: a clinicopathological review.
AB  - There has been continuing debate on the subject of malignant meningiomas, but few
      studies of large series have been reported. We present our experiences with 25
      atypical and malignant meningiomas operated on at Henry Ford Hospital between
      1976 and 1990. A total of 319 primary intracranial meningiomas were operated on
      during this period; of these, 294 (92%) were benign, 20 (6.26%) atypical, and 5
      (1.7%) malignant. We used a modified histological grading system, based primarily
      on World Health Organization criteria of malignancy (hypercellularity, loss of
      architecture, nuclear pleomorphism, mitotic index, tumor necrosis, and brain
      invasion), to define atypical and malignant meningiomas. Each of these criteria
      was given a score from 0 to 3, and then partial scores were added to obtain
      cumulative scores. These total scores were then used to determine what is benign,
      atypical, and malignant. The peak incidence of atypical and malignant meningiomas
      was in the seventh and sixth decades, respectively. The predominance of female
      patients with benign meningiomas was not observed in the nonbenign group. The
      male:female ratio for atypical and malignant meningiomas was 1:0.9 versus 1:2.3
      for benign meningiomas (P = 0.024). The most common presenting symptom and
      physical sign in our patients was paresis. In reviewing their radiographic
      features, all patients showed moderate or marked edema on computed tomography.
      Calcification was exhibited by one patient only and "mushrooming" was seen in
      three cases. Of the 25 patients, 11 (44%) died during follow-up: 2 in the
      perioperative period, 8 within the first 5 years, and 1 died 11 years after the
      diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134010
TI  - Treatment of giant intradural (perimedullary) arteriovenous fistulas.
AB  - Ten patients with giant intradural spinal arteriovenous fistulas (perimedullary
      Types II and III) were treated with embolization alone (three patients) or in
      combination with surgery (seven patients). Their ages at the time of treatment
      ranged from 2 to 40 years, with a mean of 19.5 years. The indications for
      treatment included progressive myelopathy in five patients, spinal subarachnoid
      hemorrhage in four, and acute paraplegia in one. Associated conditions included
      Rendu-Osler-Weber syndrome in two patients, and Cobb's syndrome in two patients.
      In one patient, the cause of the fistula may have been related to epidural
      anesthesia traumatizing a low tethered cord. Angiographically, the fistulas were
      subclassified in three groups: a single-hole fistula supplied by a single feeding
      medullary artery (three patients); a single-hole fistula supplied by multiple
      medullary arteries (three patients); and multiple separate fistulas supplied by
      multiple medullary arteries (four patients). Eight patients were classified as
      perimedullary Type III and two as perimedullary Type II. Embolic agents were
      delivered from transarterial routes in 14 procedures and transvenous routes in 2
      procedures. A total of 16 embolizations and 8 operations were performed in 10
      patients. Seven patients were cured of their fistula (as demonstrated by
      angiography), two patients had 5% residual filling and are scheduled for future
      therapy. One refused a follow-up angiographic examination. Complications related
      to embolization included rupture of the anterior spinal artery by a detachable
      balloon, resulting in transient worsening of paraplegia with recovery to
      baseline. Transient worsening of symptoms after surgery was common, but all
      patients returned to baseline or better. Dramatic improvement was observed in
      four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134009
TI  - Management and outcome of low-grade astrocytomas of the midline in children: a
      retrospective review.
AB  - Low-grade astrocytomas of the midline of the brain can be difficult to manage
      because of their location. To evaluate treatment and outcome, we performed a
      retrospective study of children with midline low-grade astrocytomas admitted to
      The Hospital for Sick Children between 1976 and 1991. Eighty-eight children with
      biopsy-proven low-grade astrocytomas were identified. Forty-three tumors occurred
      in the optic pathways or hypothalamus, 13 in the thalamus, 7 in the pineal
      region, 14 in the midbrain, and 11 in the medulla. Patient follow-up ranged from
      6 months to 15 years, with a mean of 4 years, 9 months. Overall outcome was
      related to the extent of resection, histological type, and location. Partial
      resections were often associated with involution of the tumor. Response to
      radiation was variable, and serious sequelae were observed. Thirty-three patients
      experienced recurrence, often with a good response to subsequent surgery;
      however, 12 of these patients died. The probability of survival was calculated to
      be 96% at 1 year, 91% at 5, and 80% at 10 years. Our study suggests that
      resection should be considered in all patients, both at presentation and
      recurrence.

PMID- 8134011
TI  - De novo aneurysms: special multiple intracranial aneurysms.
AB  - Very few patients develop completely new intracranial aneurysms during long-term
      follow-up after successfully treated subarachnoid hemorrhages. Aneurysms
      appearing after therapeutic ligation of proximal major vessels or failed surgery
      and the growth of previously noticed infundibular widenings or small aneurysms
      must be excluded to find true de novo aneurysms. Twenty-nine true cases of de
      novo aneurysms were reported in the literature, and 13 additional cases of our
      own are described. The incidence of de novo aneurysm formation and rupture is 63
      per 100,000 per year in patients known to have a subarachnoid hemorrhage. Young
      patients could benefit from long-term neuroradiological follow-up.

PMID- 8134012
TI  - Combined endovascular and neurosurgical approach for paraclinoid internal carotid
      artery aneurysms.
AB  - The authors review the surgical management of nine complex paraclinoid aneurysms
      treated with the endovascular balloon catheter technique. With the patient under
      general anesthesia, the balloon catheter was guided into the feeding artery of
      the aneurysm by the Seldinger technique. After the aneurysm was exposed, the
      balloon was inflated temporarily to prevent premature rupture and to facilitate
      the dissection of the aneurysm. For the larger paraclinoid aneurysm, the double
      lumen catheter was introduced into the cervical internal carotid artery (ICA).
      After temporarily trapping the aneurysm by balloon occlusion of the cervical ICA
      and clipping the intracranial ICA distal to the aneurysm, retrograde aspiration
      was performed to collapse the aneurysm. The complete collapse of the large
      aneurysm by this technique allows an easier dissection of the aneurysm and a
      safer application of suitable clips. Such a retrograde suction decompression
      method was used in six large aneurysms. Intraoperative digital subtraction
      angiography was performed in all cases after the aneurysmal clipping; in three
      aneurysms, repositioning the clip was required. Only one case of embolic
      complication was related to the vessel catheterization in this series, which was
      discovered during the operation. An embolectomy was performed immediately, and
      there were no postoperative sequelae. We conclude that the combined endovascular
      and neurosurgical approach, particularly for the large ICA aneurysms, which are
      difficult to control proximally, can be a useful method of treatment. To prevent
      complications related to thrombus formation, further refinement in the balloon
      catheter itself is still needed.

PMID- 8134013
TI  - Transitional cavernous aneurysms of the internal carotid artery.
AB  - Twenty-three cases of transitional cavernous aneurysms are presented. Aneurysms
      of this subgroup (of a total of 118 cases of cavernous sinus aneurysms) arise
      entirely from within the cavernous sinus but project into the extracavernous
      intradural subarachnoid space, thus resembling other intracranial aneurysms in
      their increased risk of rupture. Six aneurysms were small (less than 15 mm), 6
      were large (15 to 25 mm), and 11 were giant (more than 25 mm). Thirteen patients
      (57%) had a subarachnoid hemorrhage, nine patients (39%) had compressive
      symptoms, and one patient (4%) was asymptomatic. A direct surgical approach was
      performed successfully in 18 cases (78%), and indirect bypass methods were
      performed in 5 cases. The overall surgical outcome was excellent in 87% of the
      patients, with three complications (13%) including one fatality. It is suggested
      that this subgroup is a different entity from other cavernous or extracavernous
      aneurysms and should be managed aggressively with direct clipping whenever
      possible because of the increased risk of subarachnoid hemorrhage. A simplified
      numerical classification system of clinoidal-region aneurysms of the internal
      carotid artery (including transitional aneurysms) is also proposed.

PMID- 8134014
TI  - Which neuropsychological deficits are hidden behind a good outcome (Glasgow = I)
      after aneurysmal subarachnoid hemorrhage?
AB  - A series of 31 patients with good neurological 6-month outcomes (Glasgow Outcome
      Scale = I) was examined with a battery of cognitive tests 1 to 5 years after
      aneurysmal subarachnoid hemorrhage (SAH) and early operation. The results showed
      a marked disability in 28 to 62% of these patients in the subtests of a complex
      choice reaction task. Short-term memory was impaired in 53% of the patients
      neuropsychologically examined, whereas 21% of them had a reduced long-term
      memory. Concentration was impaired in 7 to 16% of the SAH patients. Also, 10% of
      the patients rated Glasgow Outcome Scale = I had an indication for an aphasic
      language disturbance. Multivariate analysis proved significant harmful effects of
      the severity of the bleeding seen on computed tomographic scan (Fisher scale) on
      information processing and word-finding capacity. Patients who were older at the
      time of the SAH were significantly more disturbed in concentration, short-term
      memory, and information-processing capacity at follow-up. It can be concluded
      from these results that a good neurological outcome (Glasgow Outcome Scale = I)
      does not exclude persisting neuropsychological deficits. Therefore, the value of
      the clinical use of the Glasgow Outcome Scale is limited. As a consequence, a
      differentiated neuropsychological examination is proposed to evaluate the exact
      outcome of SAH patients.

PMID- 8134015
TI  - Visual attention revealed by an illusion of motion.
AB  - Attention is a mechanism to select sensory information. It is a modulatory
      process which normally cannot be observed as overt responses. A new
      psychophysical method using an illusion of motion perception allowed us to
      visualize the field of the magnitude of attention and its dynamic changes. Based
      on our experiments using this method we suggest that (1) both passive (bottom-up)
      and active (top-down) attention exert their effects on the early stages of visual
      processing, (2) active attention can quickly and briefly be replaced by passive
      attention induced by an external event, but can be restored in about 400 ms, and
      (3) attention is directed to an object, not space, and follows the object as it
      moves.

PMID- 8134016
TI  - Effects of differential rearing on the structure of perforated synapses in the
      granule cell layer of the rat's accessory olfactory bulb.
AB  - The effects of differential rearing on synaptic morphology in the granule cell
      layer of the accessory olfactory bulb (AOB) were examined in adult rats. Forty
      day-old male rats were housed in one of three ways: individually (isolated
      condition, IC); with four males per cage (unisexual condition, UC); or with two
      males and two females per cage (social condition, SC). After 2 months, the
      animals were killed for electron microscopy. Two types of synapses were
      classified: (1) perforated synapses, which are characterized by discontinuities
      in their postsynaptic thickenings, and (2) non-perforated synapses. The length of
      the synaptic contact zone as well as the area and the length of the perimeter of
      both the pre- and postsynaptic terminals were measured in each observed synapse.
      For perforated synapses, the length of the synaptic contact zone was
      significantly greater in the UC and the SC than in the IC. For the presynaptic
      terminals of perforated synapses, the area was greater in the UC and the SC than
      in the IC, and the length of the perimeter was greater in the UC than in the IC.
      In contrast, there was no difference in the area and the length of the perimeter
      among the three groups for postsynaptic terminals. For non-perforated synapses,
      there was no statistically significant difference in either the area or the
      length of the perimeter of pre- and postsynaptic terminals among the three
      experimental groups, although the length of the synaptic contact zone was greater
      in the SC than in the IC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134017
TI  - Anti-idiotypes against an anti-haloperidol antibody bind to sigma receptors.
AB  - Anti-idiotypic monoclonal antibodies that interact with the binding site of sigma
      receptors were generated. First, BALB/c mice were immunized with a haloperidol
      bovine serum albumin conjugate, and monoclonal anti-haloperidol antibodies that
      recognize the piperidinyl moiety of haloperidol molecule were obtained. Second,
      for generation of anti-idiotypic antibodies, BALB/c mice were immunized with the
      anti-haloperidol monoclonal antibodies coupled to keyhole limpet hemocyanin. Anti
      idiotypic antisera and three hybridomas secreting anti-idiotypic monoclonal
      antibodies were obtained. All of them were shown to inhibit [3H]haloperidol
      binding to the anti-haloperidol antibodies. The anti-idiotypes were potent in
      displacing the binding of [3H]haloperidol to rat brain sigma receptors.
      Furthermore, they significantly immunoprecipitated the sigma receptors from a
      detergent-solubilized preparation. These findings demonstrate the generation of
      anti-idiotypic monoclonal antibodies specifically interacting with membrane-bound
      and solubilized sigma receptors.

PMID- 8134018
TI  - Phototaxic behavior and the retinotectal transport of horseradish peroxidase
      (HRP) in surgically created cyclopean salamander larvae (Ambystoma).
AB  - Negative phototaxis (NP) was used to evaluate the recovery of vision in albino
      axolotl larvae with one eye discarded and the other transplanted either to the
      orbit (orthoclops) or to the top of the head (cyclops). NP was assessed at
      approximately 1, 2 and 3 months postoperatively, using an automated, infrared
      monitor. Some 88% of the orthoclopes and 64% of the cyclopes recovered NP.
      However, among the cyclopes that did recover, the quantitative aspects of NP were
      virtually the same as those of the orthoclopes. That the cyclopean eye can
      regenerate retinotectal pathways was established by anterograde tracing of
      horseradish peroxidase (HRP). But where previously uninjured animals transported
      HRP to the contralateral tectum, both the cyclopes and the orthoclopes
      distributed the enzyme to the left and right tectal halves. Heavy deposits of HRP
      were found in the tecta of some animals that lacked NP. To find out if an optic
      tectum is actually required for NP, a series of ablation experiments were
      performed, using Ambystoma punctatum larvae. Tectectomy had the same effect on NP
      as bilaterally extirpating the eyes or intracranially severing both optic nerves,
      i.e. removing the tectum abolished NP. THE RESULTS: (1) confirm the efficacy of
      the ectopic eye in the cyclops preparation; (2) show that the ectopic eye can
      regenerate retinotectal pathways; (3) indicate that retinotectal contact is a
      necessary but insufficient condition for NP.

PMID- 8134019
TI  - Dopamine output upon death reflects intraneuronal aspects while alive:
      accumulation of releasable dopamine during tetrodotoxin perfusion.
AB  - Intraneuronal and extracellular dopamine (DA) metabolism in rat striatum during
      inhibition of neurotransmission processes by tetrodotoxin (TTX) perfusion was
      examined by analysis of the striatal DA content and the amount of initial post
      mortem DA output. In spite of there being an excess amount of DA already present
      in the striatum, the contents of DA and its metabolites were increased time
      dependently by TTX perfusion through a microdialysis membrane. A massive increase
      in extracellular level of DA occurred immediately after death. The amount of the
      post-mortem DA output was further increased in proportion to the preceding TTX
      perfusion time. The ratio of the amount of post-mortem DA output to the striatal
      DA content was also increased by previous perfusion with TTX. Verapamil, a Ca2+
      channel blocker, delayed the appearance of the peak of the DA output. These
      results suggest that releasable DA accumulates in neurons during TTX perfusion,
      and that the early part of the DA output upon death reflects intraneuronal
      aspects of DA metabolism while the animal is alive.

PMID- 8134020
TI  - Neural mechanisms of the reflex inhibition and excitation of gastric motility
      elicited by acupuncture-like stimulation in anesthetized rats.
AB  - The effects of acupuncture-like stimulation of the various segmental areas on
      gastric motility were examined in anesthetized rats. An acupuncture needle
      (diameter 340 microns) was inserted into the skin and underlying muscles at a
      depth of 4-5 mm and was twisted right and left once every second for 60 s.
      Gastric motility in the pyloric region was measured with the balloon method.
      Gastric motility was inhibited by acupuncture-like stimulation applied to the
      abdomen and lower chest region, and was often excited when the limbs were
      stimulated, in all cases in which stimuli were delivered to the skin and muscles,
      the skin alone, and the underlying muscles alone. The inhibitory gastric response
      to abdominal stimulation was accompanied by an increase in the activity of the
      gastric sympathetic efferent nerve and was abolished by severance of either the
      sympathetic nerve branches to the stomach or the lower thoracic spinal nerves.
      The abdominal stimulation enhanced the activity of the lower thoracic spinal
      afferent nerves. The excitatory gastric response to hindpaw stimulation was
      accompanied by an increase in the activity of the gastric vagal efferent nerve
      and was abolished by severance of either the bilateral vagi or the femoral and
      sciatic nerves. The hindpaw stimulation enhanced the activity of the femoral and
      sciatic afferent nerves. In the spinalized animals, the inhibitory gastric
      response elicited by abdominal stimulation was present, and the hindpaw
      stimulation did not produce any gastric response. We conclude that the inhibitory
      gastric response elicited by acupuncture-like stimulation of the abdomen is a
      reflex response. Its afferent nerve pathway is composed of abdominal cutaneous
      and muscle afferent nerves, the efferent nerve pathway is the gastric sympathetic
      nerve, and its reflex center is within the spinal cord. The excitatory gastric
      response elicited by acupuncture-like stimulation of a hindpaw is also a reflex
      response. Its afferent nerve pathway is composed of hindpaw cutaneous and muscle
      afferent nerves, the efferent nerve pathway is the gastric vagal efferent nerve,
      and its reflex center requires the presence of the brain. Furthermore, the
      excitatory and the inhibitory gastric reflex responses were not influenced by
      i.v. administration of naloxone (0.4-4 mg/kg), suggesting that endogenous opioids
      are not involved in the present reflexes.

PMID- 8134021
TI  - Retinal differentiation from multipotential pineal cells of the embryonic quail.
AB  - Pineal cells of the embryonic quail are multipotent stem cells which are able to
      differentiate in vitro into pigmented epithelial cells, lens cells and skeletal
      muscle fibers. Neuronal expression was added in this study in the repertory of
      differentiating potency of pineal cells. We used immunohistochemical methods to
      characterize neuronal properties with antibodies against serotonin, GABA,
      tyrosine hydroxylase and neuron-specific antigen (HPC-1) in addition to the
      enzyme histochemistry for acetylcholinesterase activity. Cells in the culture
      were found to be positively stained with these methods, suggesting that embryonic
      pineal cells are neuropotent to differentiate various types of neuronal cells. We
      have studied the culture conditions which favor increment of neuronal cells with
      extension of neuritic processes, and we have found that neuronal cells are
      maintained for quite a long period under suppressive conditions of DNA synthesis
      and under the effect of basic fibroblast growth factor (FGF). Suppression of DNA
      synthesis was achieved by the addition of aphidicolin, an inhibitor of DNA
      polymerase alpha, in the medium. Time lapse videograph revealed two different
      cell types participated in neurogenesis; a minor population of small round cells
      and a major one of flat epithelial cells. Since embryonic quail pineal cells have
      been shown to differentiate into two types of photoreceptors, the present results
      show wider retinal potency of cell differentiation by embryonic pineal cells. The
      cessation of DNA synthesis as well as growth factor(s) may be positively involved
      in the mechanisms of determination and differentiation of pineal neurons.

PMID- 8134022
TI  - Changes in cranial and rectal temperature, blood pressure and arterial blood gas
      during and after unilateral and bilateral forebrain ischemia in Mongolian
      gerbils.
AB  - Transient forebrain ischemia was produced by occluding the common carotid
      arteries, either unilaterally or bilaterally, in Mongolian gerbils under
      halothane anesthesia. After 20-min ischemia, the cranial temperature measured in
      the temporal muscle decreased compared to the preischemic level, the decrease
      being larger after the bilateral than after the unilateral occlusion. After
      recirculation, cranial temperature recovered promptly to the preischemic level in
      the unilateral group, while it was elevated to above the preischemic level in the
      bilateral group. The rectal temperature also decreased with a similar time
      course. During 30-min ischemia, the blood pressure of both groups increased to
      above the preischemic level, the increase being larger in the bilateral group
      than in the unilateral group. After recirculation, blood pressure of the
      unilateral group recovered promptly to the preischemic level, while that of the
      bilateral group decreased to below the preischemic level. When forebrain ischemia
      was produced immediately after cessation of halothane inhalation, blood pH, PaO2
      or PaCO2 did not change significantly from the control level. However, these
      values showed larger variation in the bilateral group than in the unilateral
      group. Unilateral occlusion in preselected gerbils provided a good model of
      transient brain ischemia, giving rise to uniform experimental results.

PMID- 8134023
TI  - GABAB modulation of neuronal activity related to visually guided movement in the
      monkey premotor cortex.
AB  - The effects of the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen
      and the GABAA receptor antagonist bicuculline methiodide on the activities of the
      same neurons in the premotor cortex of two monkeys while they performed a
      visually guided task with a GO or NO-GO response were investigated. While
      bicuculline methiodide induced excitatory responses in all of the task-related
      neurons examined, baclofen induced inhibitory responses in 75% of the examined
      neurons and excitatory responses in 25% of the neurons. The results indicate
      that, in the monkey premotor cortex, not only GABAA but also GABAB receptors are
      involved in GABAergic modulation of neuronal activities related to the visually
      guided behavioral performance.

PMID- 8134024
TI  - Childhood origins of lifestyle-related risk factors for coronary heart disease in
      adulthood.
AB  - Research over the past 40 years clearly points to childhood as a critical period
      when dietary and lifestyle patterns are initiated which have longterm
      implications for coronary heart disease risk in adult life. Smoking, high
      habitual dietary intake of total fat and saturated fat, low exercise level, and
      excessive alcohol consumption often occur in family aggregates. They are
      correlated with elevated serum cholesterol, obesity, and hypertension in
      children, as well as with a predisposition to premature death from coronary heart
      disease. Intervention studies in children and adolescents show, however, that
      these lifestyle-risk factors are controllable through education and dietary
      counselling of the affected individual and their family. Equally important are
      the emerging data in adults showing that vigorous longterm intervention involving
      reduction of dietary fat and work-related stress, increased exercise, and
      elimination of smoking all contribute to a significant improvement in coronary
      perfusion. Hence, effective dietary and lifestyle management of coronary heart
      disease can occur at early or later stages of the disease and needs better
      support from health authorities at the national and international level.

PMID- 8134025
TI  - Nutrition-related diseases and dietary change among Third World immigrants in
      northern Europe.
AB  - Immigrants from the third world are more prone to acquire nutritional deficiency
      diseases, such as rickets, osteomalacia and iron deficiency anemia than the rest
      of the population in the recipient countries. Lately, evidence is also emerging
      that some immigrant groups are particularly susceptible to diseases related to
      overnutrition, such as coronary heart disease and non-insulin dependent diabetes.
      The purpose of this review article is to give a holistic view of the nutrition
      related diseases and disorders among immigrants. It deals with the prevalence of
      these diseases among immigrants in Northern European countries, and looks into
      some of the hypotheses, which have been put forward to explain why immigrant
      groups are more prone to acquire these diseases than the rest of the population.
      The focus of this part of the paper is the process of dietary change after
      migration. The practical implications of the findings from the literature review
      are then discussed.

PMID- 8134026
TI  - What is nutritional medicine?
AB  - Nutritional Medicine is based on the principle that nutrients, including
      essential micronutrients, are required for the proper functioning of all the
      biochemical processes on which our bodies depend. Therefore, when treating
      symptoms or diseases, we look for the underlying causes which, although often
      partly genetic, are usually very much tied up with nutritional and environmental
      factors. This is in contrast to the tendency in the conventional medical approach
      to treat symptoms by means of drugs or surgery.

PMID- 8134027
TI  - Cardiovascular disease.

PMID- 8134028
TI  - Feeding babies.

PMID- 8134029
TI  - The world health evidence. The mother is the key to the next generation.

PMID- 8134031
TI  - Don't change the environment.

PMID- 8134030
TI  - Maternal nutrition and cardiovascular disease.

PMID- 8134032
TI  - Lesbian, single and geriatric women: to breed or not to breed?

PMID- 8134033
TI  - The evolving doctrine of corporate liability.

PMID- 8134034
TI  - AONE's National Consumer Summit. American Organization of Nurse Executives.

PMID- 8134035
TI  - All politics is local: and other rules....

PMID- 8134036
TI  - Managed care software: the next generation (2).

PMID- 8134037
TI  - Nurse manager: a key role in clinical outcomes.
AB  - As a central partner in the business of the hospital, the nurse manager's focus
      is on the delivery of high-quality care resulting in desired clinical outcomes at
      controlled costs. These outcomes require a partnership for patient care. Nurse
      managers develop and empower staff; forge collaborative and team relationships
      within nursing and with other disciplines and departments; and help to transform
      the hospital culture. Roles, responsibilities, educational preparation and
      experience requirements are discussed as well as the significance of
      collaborating with other healthcare members.

PMID- 8134038
TI  - Investigating narcotic diversion.
AB  - Management is responsible for developing policies and procedures not only for
      handling of narcotics but also for investigating and intervening in drug-related
      incidents. Both nurse managers and peers often feel ill-prepared to deal with
      drug impairment. Nurses who suspect a peer of substance abuse should notify the
      manager, who must cross-check all medication documentation and look for the many
      tell-tale signs of narcotic diversion. If sufficient evidence is discovered, the
      nurse must be confronted and directed to some type of peer assistance or other
      recovery program.

PMID- 8134039
TI  - Nursing/pharmacy interface: a TQM project.
AB  - W. Edwards Deming's seven-step quality improvement process provided a sequential
      pathway to facilitate problem-solving allowing the pharmacy and nursing
      departments to formulate a systems perspective rather than an individual point of
      view. Both departments identified problems with the Medication Administration
      Record and defined three key outcomes needed to signify process improvement.

PMID- 8134040
TI  - QA/QI and nursing competence: a combined model.
AB  - A Quality Assessment/Improvement/Competency Model, developed at Norwalk Hospital,
      provides objective data which fulfills Joint Commission QA/QI requirements.
      Simultaneously, this monitoring system provides for evaluation of clinical
      competence.

PMID- 8134041
TI  - The mock survey: preparing for JCAHO visit.
AB  - For chief nursing executives, the evaluation process for accreditation by
      regulatory agencies can evoke considerable anxiety. A self-evaluation tool that
      could prove helpful in decreasing anxiety is the mock survey which simulates the
      site visit process and provides standards review akin to JCAHO parameters. The
      primary goals of the mock survey are to educate staff, reduce anxiety, display
      support and provide for meeting any identified needs.

PMID- 8134042
TI  - Evaluating planned change theories.
AB  - A criterion-referenced instrument was developed for determining to what extent a
      planned change theory meets predetermined criteria of significance, agreement
      with nursing's perspective, clarity and consistency, economy, generality,
      practicality and testability. These criteria form the basis of a quantitative
      instrument composed of 31 evaluation questions to determine a planned change
      theory's suitability for nursing situations. This instrument combines well with
      qualitative evaluations of theory goodness and with change theorists' ratings of
      their own theories. Psychometric evaluation of the instrument is in progress.

PMID- 8134043
TI  - Nursing productivity in rural hospitals.
AB  - Monitoring of direct and indirect nursing costs and length of stay is essential
      for rural hospitals to survive, especially if a high percentage of revenues is
      from DRG reimbursement. Furthermore, the costs and productivity of other
      departments that directly affect nursing productivity must be assessed. Nurse
      administrators should determine accurately the nursing costs and nursing
      productivity for the high volume DRGs at their hospital. Nurses must be able to
      demonstrate to hospital administrators, insurance companies and consumers that
      nursing care is cost-efficient, high-quality and effective.

PMID- 8134044
TI  - Quality, the old fashioned way.

PMID- 8134045
TI  - Shaping elder care in the acute setting.
AB  - Caring for the elderly in the 1990s poses a challenge necessitating exploration
      of a number of variables which affect the patient, the family and the setting in
      which care is provided. Hence, nursing leadership is compelled to shape the
      processes of elder care. The authors share strategies, insights and approaches to
      address this growing mandate.

PMID- 8134046
TI  - Understanding hospitality.
AB  - Bridging patient/"customer" issues and business aspects can be aided through
      developing a specific nursing basis for hospitality. The ancient practice of
      hospitality has evolved into three distinct levels: public, personal and
      therapeutic. Understanding these levels is helpful in integrating various
      dimensions of guest relations programs in hospitals into a more comprehensive
      vision. Hospitality issues must become a greater part of today's nursing
      management.

PMID- 8134047
TI  - Implementing self-directed teams.
AB  - The "self-directed team" concept is an innovative approach in the healthcare
      setting. Long-term benefits of customer satisfaction and quality improvement are
      consistent with concepts of total quality improvement and patient-focused care.
      Initial investment of time and money pays off in low turnover and marked employee
      and patient satisfaction.

PMID- 8134048
TI  - Needleless i.v. therapy: comparing three systems for safety.
AB  - Three needleless systems were compared for general usability and cost. A closed,
      one-piece, nonmechanical unit was chosen as it proved safe in both peripheral and
      central lines, required minimal inservicing and yielded significant cost savings.

PMID- 8134049
TI  - PACE: an innovative approach to fostering teamwork. People Appreciating Clinical
      Excellence.

PMID- 8134050
TI  - From "sizing up" to "settling in".

PMID- 8134051
TI  - Needed changes in obstetric-gynecologic training.

PMID- 8134052
TI  - Cervical pregnancy: case reports and a current literature review.
AB  - The increasing number of reports of successful conservative treatment of cervical
      pregnancy, such as using the folinic acid antagonist methotrexate, constitutes a
      breakthrough in the management of this unusual but potentially life-threatening
      complication of pregnancy. We are reporting two cases of cervical pregnancy, both
      diagnosed in the first trimester of pregnancy. The first one was successfully
      treated by transvaginal ultrasound-guided administration of 2 mEq KCI
      intraamniotically in order to stop the fetal heart activity, followed by
      administration of 84 mg of methotrexate intraaminiotically (1 mg/kg); whereas in
      the second case, we encountered a technical failure of the above method. Both
      patients expressed desire to maintain their reproductive capability. These two
      cases gave us the opportunity to review the recent literature on cervical
      pregnancy.

PMID- 8134053
TI  - Reproductive function and contraception in the postpartum period.
AB  - The postpartum period is a time of major cellular and hormonal change enabling
      the return of pelvic organs and the hypothalamic-pituitary-ovarian axis to the
      nonpregnant state. Breast-feeding modifies this change and maintains the
      endocrine profile and uterine endometrium in a "static" state. In nonlactating
      women, menstruation returns on average by day 55 to 60 postpartum and ovulation
      returns on average by day 40 to 50 postpartum. Breast-feeding prolongs the return
      of menstruation to some 8 to 15 months postpartum and the first ovulation on
      average was between 30 to 40 weeks postpartum. However, in breast-feeding women,
      the return of menstruation and ovulation can be quite variable and is influenced
      by the pattern of breast-feeding, in particular, the intensity and pattern of
      suckling. There is concern that breast-feeding, although an effective
      contraceptive on a wide population scale, is unpredictable for the individual. An
      overall pregnancy rate of 2 to 10 per cent during lactational amenorrhea has been
      reported. Barrier methods, intrauterine contraceptive devices, and progestogen
      only contraceptives are some of the highly effective and most commonly used
      additional methods of contraception by lactating women. Other methods of
      contraception during this period include the use of periodic abstinence and
      combined oral contraceptives. This paper provides an overview of postpartum
      reproductive function in relation to breast-feeding and the use of contraception
      in this unique period.

PMID- 8134054
TI  - Metabolic changes in diabetic and nondiabetic subjects during pregnancy.
AB  - Diabetes mellitus with its resulting derangement of various metabolic fuels,
      carbohydrates, amino acids, lipids, and ketones has the potential to adversely
      affect the developing fetus. Therefore, strict glycemic control in pregnancy has
      become the standard of care in modern obstetrics. A considerable amount of
      research has been undertaken into the metabolic changes that occur during
      pregnancy in both women with insulin-dependent diabetes and gestational diabetes.
      This paper will review current research in normal and diabetic pregnancies both
      in the fasting and fed states as well as during episodes of hypoglycemia. In
      normal pregnancy insulin secretion increases throughout gestation whereas
      peripheral insulin sensitivity is decreased. Fasting levels of plasma glucose are
      reduced by approximately 10 per cent during the first trimester. Maternal amino
      acid levels are also reduced in normal pregnancy, although cholesterol and
      triglyceride levels are increased, most dramatically in the second trimester. As
      gestation advances, progressively increasing amounts of insulin antagonistic
      hormones are secreted by the placenta. This leads to gestational diabetes in 2 to
      3 per cent of women who exhibit hyperglycemia despite an increased insulin
      response to oral glucose as well as an increased insulin/glucagon ratio. In
      insulin dependent diabetes mellitus, the insulin-deficient state results in
      fasting and postprandial hyperaminoacidemia, hyperlipidemia, and hyperglycemia.
      These metabolic changes and the resulting hyperglycemic milieu can lead to fetal
      macrosomia that will result in maternal and fetal morbidity. Therefore,
      normalization of these fuels with the use of intensive insulin regimens is the
      goal of therapy during pregnancy.

PMID- 8134055
TI  - Nonfatal venous air embolism during cesarean section: a case report and review of
      the literature.
AB  - Venous air embolism occurs in more than half of all cesarean sections.
      Predisposing factors in pregnancy include uterine surgery and manipulation,
      hypovolemia, and maternal positioning. The presence of an intracardiac septal
      defect and use of certain anesthetic agents place the patient at greater risk of
      fatal air embolus. The sudden development of hypotension, hypoxia, and a drop in
      end-tidal CO2 are typical signs of this condition. Supportive therapy includes
      flooding the surgical field with normal saline, placing the patient in reverse
      Trendelenburg with a left-lateral tilt, and discontinuation of nitrous oxide
      anesthesia. We report a case that was diagnosed and successfully managed during a
      cesarean section and review the literature on prophylaxis, diagnosis, and therapy
      of this condition. A high index of suspicion and use of precordial Doppler
      studies in the future will permit earlier diagnosis and therapy and decreased
      mortality from this common condition. The phenomenon of venous air embolism in
      the intrapartum period has been well described in the anesthesia literature but
      there have been few case reports of patients having this complication in the
      recent obstetrical literature. We wish to describe the clinical course and
      successful management of a patient with this complication during cesarean section
      and provide a review of the literature on the phenomenon of venous air embolism
      in the obstetrical patient with particular emphasis on pathophysiology,
      detection, and treatment.

PMID- 8134056
TI  - Strategies for the prevention of early-onset neonatal group B streptococcal
      sepsis: a decision analysis.
AB  - OBJECTIVE: To perform a decision analysis to understand better the implications
      of 19 potential group B streptococcus screening and treatment strategies.
      METHODS: We searched the literature to locate appropriate articles from which to
      derive probability estimates. Using decision analysis, we determined the likely
      outcomes of 19 group B streptococcus screening and treatment strategies and
      focused on three main outcomes: 1) number of expected cases of early-onset
      neonatal group B streptococcal sepsis, 2) percentage of gravidas treated with
      intrapartum antibiotics, and 3) total costs. RESULTS: The strategy recently
      recommended by two committees of the American Academy of Pediatrics (universal 28
      week maternal rectovaginal group B streptococcal culture and treatment of culture
      positive, high-risk patients in labor) is among the least effective at reducing
      neonatal sepsis and the most costly. Strategies based on the currently available
      rapid streptococcus identification tests are ineffective at reducing neonatal
      sepsis and are costly. Three strategies outperform the rest: 1) Universal
      intrapartum maternal antibiotic treatment is the most effective strategy in
      reducing early-onset neonatal group B streptococcal sepsis (6% of expected) and
      is also the least costly; 2) intrapartum treatment based solely on risk factors
      (recently endorsed by ACOG) lowers the rate of neonatal sepsis to 31% of expected
      with an 18% maternal treatment rate and low total costs; and 3) universal 36-week
      maternal culture, and treatment of all patients experiencing preterm birth and
      all culture-positive patients results in 14% of expected neonatal sepsis, with a
      27% maternal treatment rate and low total costs. CONCLUSION: Given the present
      state of knowledge, three strategies emerge from this decision analysis as most
      optimal for the prevention of early-onset neonatal group B streptococcal sepsis:
      universal treatment, treatment based on risk factors, and treatment based on
      preterm delivery and 36-week culture status.

PMID- 8134057
TI  - Late postpartum eclampsia revisited.
AB  - OBJECTIVE: To describe the clinical and neurologic findings in patients with late
      postpartum eclampsia (convulsions beginning more than 48 hours, but less than 4
      weeks, after delivery). METHODS: This study evaluated all patients with the
      diagnosis of late postpartum eclampsia managed at our institution between August
      1977 and July 1992. RESULTS: There were 54 cases of late postpartum eclampsia
      among a total of 334 cases of eclampsia during the study period. Late postpartum
      eclampsia constituted 56% of total postpartum eclampsia and 16% of all cases of
      eclampsia. Convulsions began from postpartum days 3-23 (mean 6). Thirty women
      (56%) had been identified as preeclamptic before their convulsions. A history of
      either severe headache or visual disturbances before convulsion was elicited in
      83% of the patients. During the study period, eight women not included in the
      study group had late postpartum seizures attributed to other causes. CONCLUSIONS:
      Severe headache or visual disturbance frequently antedates late postpartum
      eclampsia. Only eight of 62 patients with late postpartum seizures had
      identifiable etiologies other than eclampsia.

PMID- 8134058
TI  - The West Los Angeles Preterm Birth Prevention Project: II. Cost-effectiveness
      analysis of high-risk pregnancy interventions.
AB  - OBJECTIVE: To examine the cost-effectiveness of the West Los Angeles Preterm
      Birth Prevention Project. METHODS: Maternal and neonatal care data were collected
      on all preterm deliveries (150) and a random sample of term deliveries (140) from
      high-risk patients at both experimental and control clinic sites. Costs were
      determined for prenatal care, inpatient preterm labor, delivery and postpartum
      care, and newborn care. Cost calculations, weighted by the actual proportions of
      term and preterm births, were confirmed with square-root transformation and
      trimmed mean (2%) values. RESULTS: When compared to control clinic high-risk
      patients, experimental clinic high-risk patients had an average cost savings of
      $2196 for newborn care (P = .02), resulting in a net savings of $1768 per high
      risk mother-infant pair. Births before 32 weeks' gestation accounted for the
      greatest mean cost. CONCLUSION: Programs of comprehensive prenatal care and
      patient education may be highly cost-effective for prevention of prematurity.

PMID- 8134059
TI  - Pregnancy outcome following Mustard procedure for transposition of the great
      arteries: a report of five cases and review of the literature.
AB  - OBJECTIVE: To review outcomes and complications of pregnancies in women with
      transposition of the great arteries who had undergone the Mustard procedure.
      METHODS: Four women with transposition of the great arteries who had undergone
      Mustard procedures in childhood received their obstetric care for five
      pregnancies at three institutions in the greater Philadelphia area between 1990
      1992. Pregnancy complications and outcomes were reviewed. RESULTS: The most
      common maternal complication in pregnancy following performance of the Mustard
      procedure was cardiac arrhythmia, which required treatment in two of four
      patients. Late-onset fetal growth restriction requiring induction occurred in two
      of five pregnancies. Third-trimester oligohydramnios requiring induction occurred
      in one patient, and her second pregnancy was complicated by preterm labor and
      premature rupture of the membranes (PROM) at 33 weeks. One patient with a twin
      pregnancy developed mild preeclampsia, preterm labor, and PROM at 30 weeks. There
      were no neonatal or perinatal deaths or significant morbidity. CONCLUSION: If a
      patient with transposition of the great arteries who underwent the Mustard
      procedure is hemodynamically stable before pregnancy, good maternal and fetal
      outcome can be expected.

PMID- 8134060
TI  - Diurnal and gestational patterns of uterine activity in normal human pregnancy.
      The Uterine Activity in Pregnancy Working Group.
AB  - OBJECTIVES: To define the profile of 24-hour uterine activity in normal pregnancy
      and to correlate contraction frequency with physical activity and emotional
      stress diaries. METHODS: One hundred nine low-risk pregnant women who delivered
      at term recorded uterine contractions for 24 hours twice weekly from 20-40 weeks'
      gestation using an ambulatory monitor and kept a physical activity and emotional
      stress diary. Contractions per hour were calculated for each hour of the day and
      week of gestation, and related to physical activity and emotional stress.
      RESULTS: We analyzed 71,683 hours. No contractions were recorded in 73% of the
      hours, and fewer than four contractions per hour occurred in 96%. Significant
      inter-individual variability was noted. Contractions increased markedly with
      gestational age: The 95th percentile was 1.3 contractions per hour at 21-24
      weeks, 2.9 at 28-32 weeks, and 4.9 at 38-40 weeks. A strong clustering of
      contractions occurred at night, which became pronounced after 24 weeks (night:day
      ratio 2:1 at 28-32 weeks). To adjust for the effects of gestational age and time
      of day, contractions per hour were converted to gestation- and hour-specific
      percentiles ("contraction percentiles"). Rest was associated with a fall in
      contraction percentile by 1.25, whereas coitus increased the contraction
      percentile by 5.52 (P < .05). No changes were noted with emotional stress.
      CONCLUSIONS: This study provides normative contraction data in uncomplicated
      pregnancy. A strong diurnal rhythm is present from 24 weeks onward, with 67% of
      contractions occurring at night. Contractions per hour increase with gestational
      age but rarely exceed three per hour before term. Rest and sexual activity have
      small but measurable effects on contraction frequency.

PMID- 8134061
TI  - Cocaine exposure during pregnancy: improving assessment with radioimmunoassay of
      maternal hair.
AB  - OBJECTIVE: To compare radioimmunoassay of postpartum maternal hair samples with a
      structured maternal interview for the detection of cocaine use during pregnancy.
      METHODS: Radioimmunoassay of hair samples obtained postpartum was compared with
      self-report of cocaine use obtained by confidential, structured interviews of 405
      postpartum women. RESULTS: Cocaine or benzoylecgonine was detected in the hair
      samples of 129 of the 148 women (87%) who reported using cocaine at least once
      during pregnancy. Thirty-six of 257 women (14%) who reported that they had used
      no cocaine during pregnancy had positive hair tests. Positive hair assay with
      negative self-report was significantly more common among women who were unmarried
      (P = .001), African-American (P < .001), and multiparous (P = .035). CONCLUSIONS:
      Hair analysis is a valuable complement to maternal self-report by interview. The
      methods used together provide a useful clinical and research technique yielding a
      comprehensive estimate of gestational cocaine exposure. Either method alone may
      result in misclassification of gestational cocaine exposure.

PMID- 8134062
TI  - Tissue inhibitor of metalloproteinases: serum levels during pregnancy and labor,
      term and preterm.
AB  - OBJECTIVE: To determine the levels in serum of tissue inhibitor of
      metalloproteinases (TIMP) in pregnancy and to examine the possibility of a time
      course in relation to parturition, both term and preterm. METHODS: Serum tissue
      inhibitor of metalloproteinases was measured using an enzyme-linked immunosorbent
      assay. A cross-sectional study was conducted in 333 women during pregnancy,
      labor, and the postpartum period and in 27 nonpregnant volunteers. Longitudinal
      data were obtained from 22 women who provided a sample at term, during labor, and
      in the postpartum period. RESULTS: In uncomplicated pregnancies, serum TIMP
      levels were low from the onset of pregnancy until 37 weeks' gestation, in
      comparison to levels in nonpregnant women (P < .001). During the final weeks of
      pregnancy, levels rose and at 37-42 weeks were similar to nonpregnant levels. The
      levels did not change with the onset of labor. Serum concentrations of TIMP
      obtained during preterm labor were elevated compared to a control group of
      patients at a similar gestation who subsequently delivered at term (P < .01).
      Serum TIMP levels were significantly higher during the postpartum period than at
      all other times (P < .001). CONCLUSIONS: Changes in serum TIMP levels during and
      after pregnancy may parallel the remodeling of the extracellular matrix that
      takes place throughout this period. Further work is necessary to evaluate the
      prognostic value of TIMP for preterm labor.

PMID- 8134063
TI  - The frequency of glove contamination during cesarean delivery.
AB  - OBJECTIVE: To determine the frequency of glove contamination associated with
      fetal extraction during cesarean delivery. METHODS: The study was performed in 25
      women having scheduled or unscheduled cesarean delivery. Surgeons double-gloved
      for all procedures. Immediately before and after delivery of the fetus, the
      dorsal aspect of the fingers and hand of the surgeon's outer glove was swabbed
      with cotton-tip applicators and cultured for aerobic and anaerobic organisms.
      Only the glove from the hand that was used to deliver the infant was cultured.
      RESULTS: Nine of 25 cultures (36%, 95% confidence interval [CI] 17-55) performed
      immediately before fetal extraction were positive for staphylococci. No other
      organisms were isolated. Cultures performed following fetal extraction showed non
      staphylococcal bacteria in 11 of 14 (79%, 95% CI 58-100) laboring women and one
      of 11 (9%, 95% CI 0-26) nonlaboring women, a statistically significant difference
      (P < .01). In the laboring patients, non-staphylococcal bacteria were isolated
      with similar frequency from the dorsal aspect of the hand (seven of 14, 50%, 95%
      CI 24-76) and the fingers (ten of 14, 71%, 95% CI 47-95). These cultures yielded
      mostly bacterial species from the Enterobacteriaceae family. CONCLUSION: In
      laboring patients with ruptured membranes, delivery of the fetal head frequently
      results in contamination of the surgeon's glove with pathogenic bacteria. This
      finding may partially explain the increased frequency of post-cesarean
      endometritis associated with manual extraction of the placenta.

PMID- 8134064
TI  - Amniocentesis performed at 14 weeks' gestation or earlier: comparison with first
      trimester transabdominal chorionic villus sampling.
AB  - OBJECTIVE: To compare our initial experiences with early amniocentesis and
      transabdominal chorionic villus sampling (CVS). METHODS: We compared the
      diagnostic and pregnancy outcomes of our initial 250 patients undergoing early
      amniocentesis (at or before the 14th completed week of gestation) or
      transabdominal CVS (performed between 9.5-12.9 weeks' gestation). In both groups,
      the indication for prenatal diagnosis was advanced maternal age (35 years or
      older at estimated date of delivery). RESULTS: No diagnostic errors were made
      using either technique, and the culture failure rate for both methods was 0.8%
      (two of 250). Seven cytogenetic abnormalities in the early amniocentesis group
      and seven in the transabdominal CVS group were detected. Nine of the 250 women
      undergoing early amniocentesis reported spontaneous miscarriages following the
      procedure, compared to five in the transabdominal CVS group. The loss rates were
      3.8% in the early amniocentesis group and 2.1% in the transabdominal CVS group
      among continuing pregnancies. Frequencies of premature delivery, small for
      gestational age infants, and associated structural defects in both groups were
      comparable. CONCLUSIONS: At this time, early amniocentesis cannot be assumed to
      be equal to conventional transabdominal CVS or amniocentesis with regard to
      safety or accuracy; only a large cohort randomized study will adequately
      determine the safety and efficacy of early amniocentesis.

PMID- 8134065
TI  - Hysterectomy in the United States, 1988-1990.
AB  - OBJECTIVE: To describe patient characteristics and diagnoses associated with
      hysterectomy in the United States from 1988-1990 using data from the National
      Hospital Discharge Survey. METHODS: We analyzed data from the National Hospital
      Discharge Survey, an annual probability sample of discharges from nonfederal,
      short-stay hospitals in the United States. A population-based sample of all women
      aged 15 years or older in the United States civilian population who had a
      hysterectomy during 1988-1990 was examined to characterize factors associated
      with hysterectomy: patients' age and race, diagnoses, surgical approach, and
      oophorectomy. RESULTS: Approximately 1.7 million women had a hysterectomy during
      1988-1990. The highest rates--100.5 hysterectomies per 10,000 women--were for
      women aged 30-54 years. Total rates of hysterectomy for black women were similar
      to those for white women (61.7 and 56.5 per 10,000 women, respectively); uterine
      leiomyoma ("fibroid tumor") was reported as the primary diagnosis for 61% of
      black women and 29% of white women. Abdominal surgery was used for 75% of all
      hysterectomies. Concomitant bilateral oophorectomy was done for 37% of the women
      under 45 years old and 68% of the women 45 years or older. CONCLUSIONS: Two
      thirds of all hysterectomies for noncancerous conditions were performed for
      uterine leiomyoma or endometriosis--conditions that are most common before the
      age of menopause. Future assessments of the appropriateness of hysterectomy will
      require better understanding of these disorders. Continued monitoring of
      hysterectomy rates is critical to understanding the appropriate use of
      hysterectomy, alternative therapies for uterine disorders, and future trends in
      women's health care.

PMID- 8134066
TI  - The Maine Women's Health Study: I. Outcomes of hysterectomy.
AB  - OBJECTIVE: To assess the effect of hysterectomy for nonmalignant conditions on
      symptoms and quality of life and to identify adverse effects 1 year after
      surgery. METHODS: The Maine Women's Health Study was a prospective cohort study
      of 418 women ages 25-50 years undergoing hysterectomy for any nonmalignant
      condition. Patients recruited from the practices of 63 physicians performing
      hysterectomy throughout Maine were interviewed at the time of surgery and 3, 6,
      and 12 months later. Clinical and hospitalization data were obtained from
      physician reports and from a statewide hospital discharge data base. The primary
      outcomes of interest were symptom relief, changes in quality of life, and the
      development of new symptoms or problems during the year following surgery.
      RESULTS: The most frequent indications for hysterectomy were leiomyomas (35%),
      abnormal bleeding (22%), and chronic pelvic pain (18%). For these indications,
      hysterectomy resulted in marked improvements in a range of symptoms, including
      pelvic pain, urinary symptoms, fatigue, psychological symptoms, and sexual
      dysfunction. Significant improvements in scores for indices of mental health,
      general health, and activity were evident at 6 months and sustained at 1 year.
      New problems after hysterectomy (measured in those free of the symptom
      preoperatively) included hot flashes (13%), weight gain (12%), depression (8%),
      and lack of interest in sex (7%). CONCLUSIONS: Hysterectomy is highly effective
      for relief of symptoms associated with common nonmalignant gynecologic
      conditions. Symptom relief following hysterectomy is associated with a marked
      improvement in quality of life. New problems are reported after hysterectomy by a
      limited number of women.

PMID- 8134067
TI  - The Maine Women's Health Study: II. Outcomes of nonsurgical management of
      leiomyomas, abnormal bleeding, and chronic pelvic pain.
AB  - OBJECTIVE: To assess the effect of nonsurgical management of leiomyomas, abnormal
      uterine bleeding, and chronic pelvic pain on symptoms and quality of life.
      METHODS: We performed a prospective cohort study of women receiving nonsurgical
      management (n = 380) or hysterectomy (n = 311) for leiomyomas, abnormal uterine
      bleeding, or chronic pelvic pain. Patients recruited from the practices of 63
      physicians throughout Maine were interviewed at the outset of treatment and 3, 6,
      and 12 months later. The principal outcome measures were frequency and severity
      of physical and psychological symptoms, and quality of life as measured by
      validated indices of mental and general health and physical activity. RESULTS:
      Medical therapy for abnormal bleeding and chronic pelvic pain produced
      significant improvements in symptoms and quality of life. However, almost one
      quarter of patients initially treated nonsurgically subsequently underwent
      hysterectomy; of patients continuing nonsurgical therapy, 25% with abnormal
      bleeding and 50% with chronic pelvic pain reported substantial levels of symptoms
      after 1 year. There were no significant changes in symptoms and quality of life
      in patients treated nonsurgically for leiomyomas. New problems including
      tiredness, hot flashes, weight gain, and depression developed in 10% or less of
      women who did not report these symptoms preoperatively. A logistic regression
      analysis controlling for age, reproductive history, and severity of symptoms
      showed that hysterectomy was the factor most highly correlated with a positive
      outcome at 1 year for all three conditions. CONCLUSIONS: Many women with
      leiomyomas, abnormal bleeding, and chronic pelvic pain report improved symptoms
      over time with nonsurgical management. Hysterectomy remains an important
      alternative when conservative treatment fails.

PMID- 8134068
TI  - The modified Pereyra procedure in recurrent stress urinary incontinence: a 15
      year review.
AB  - OBJECTIVE: To assess the effectiveness and perioperative morbidity of the
      modified Pereyra procedure in the treatment of recurrent stress urinary
      incontinence. METHODS: Data of 54 patients who underwent a modified Pereyra
      procedure for the treatment of recurrent stress urinary incontinence between
      January 1, 1978, and August 1, 1992, were analyzed retrospectively regarding
      presenting symptoms, preoperative evaluation, surgical procedure, complications,
      and cure and failure rates. The patients were divided into two groups depending
      on the preoperative absence (group I) or presence (group II) of risk factors for
      repeated failure (detrusor instability, low-pressure urethra, fibrotic urethra,
      negative Q-tip test, and neurogenic incontinence). RESULTS: After a mean follow
      up of 36.3 months, the cure rate of 81.6% in group I (N = 38) was significantly
      (P = .005) higher than that in group II (N = 16; 43.8% cured). The mean time of
      occurrence of failure was 11.9 months for group I and 6.8 months for group II.
      The incidence of intraoperative complications (Pereyra suture in bladder,
      hemorrhage) for both groups was 7.4%. Immediate postoperative complications were
      found in 25.9% of all patients; these were mainly infectious processes. Late
      postoperative complications occurred in 33.3%, with the most prevalent being new
      onset urge incontinence and de novo detrusor instability (11.1%) and obstructive
      voiding dysfunction (9.3%). The rates of perioperative morbidity were not
      significantly different between the groups. CONCLUSION: The modified Pereyra
      procedure is well suited for the treatment of uncomplicated recurrent stress
      urinary incontinence, with a long-term cure rate of over 80%. However, success
      rates are significantly lower for recurrent stress incontinence in association
      with persistent risk factors for failure. In either instance, the procedure is
      associated with appreciable perioperative morbidity.

PMID- 8134069
TI  - Handedness, age at menarche, and age at menopause.
AB  - OBJECTIVE: To investigate the relation between handedness and age at menarche or
      age at menopause, as both handedness and reproductive variables have been
      suggested to be influenced by the intrauterine endocrine environment. METHODS:
      Self-reported information on handedness, age at menarche, age at menopause, and
      other demographic and reproductive variables was recorded for 10,328 women still
      menstruating or in natural menopause. These women had been selected as controls
      in a multicenter case-control study of breast cancer conducted in the 1960s. Left
      handedness (including ambidexterity) was modeled as the outcome variable through
      multiple logistic regression. RESULTS: After adjusting for center, age,
      menopausal status, age at menopause, years of schooling, and parity, there was no
      significant relation of handedness to age at menarche (odds ratio for each year
      delayed 1.01, 95% confidence interval [CI] 0.97-1.06) or age at menopause (odds
      ratio 1.00, 95% CI 0.98-1.02). CONCLUSION: These findings lend no support to the
      hypothesis that intrauterine endocrine variables associated with handedness also
      are related to reproductive variables.

PMID- 8134070
TI  - The effect of educational brochures on follow-up compliance in women with
      abnormal Papanicolaou smears.
AB  - OBJECTIVE: To determine whether women with abnormal Papanicolaou smears who
      received educational brochures at the initial booking for colposcopy were more
      likely to complete recommended treatment and follow-up after 18-24 months than
      were those who did not receive the brochures. METHODS: One hundred eight women
      participated in an earlier randomized study of the effect of educational
      brochures on emotional distress and knowledge about abnormal Papanicolaou smears.
      Their medical records were reviewed 18-24 months later for completed treatment
      and follow-up compliance. RESULTS: Women who received the brochure had more
      completed treatment and follow-up compliance (75.4%) than did those who did not
      receive the brochure (45.8%). The difference in compliance was 30% (99%
      confidence interval [CI] 6-54%, P = .002). There were no significant differences
      in age, education, marital status, or levels of emotional distress between
      subjects with complete and incomplete follow-up. Knowledge of the recommended
      number of follow-up visits was greater in women who completed follow-up
      (difference in frequency 30.4%; 99% CI 7-54%, P = .002). All women with completed
      treatment and follow-up who had received the brochure found it helpful.
      CONCLUSIONS: Given the high patient acceptability and demonstrated effectiveness
      in improving completed treatment and follow-up compliance, educational brochures
      should routinely accompany, or immediately follow, notification about abnormal
      Papanicolaou smears.

PMID- 8134071
TI  - Laparoscopic management of adnexal cystic masses in postmenopausal women.
AB  - OBJECTIVE: To evaluate laparoscopic treatment of postmenopausal women with an
      adnexal cystic mass predicted to be benign. METHODS: Selection criteria were
      transvaginal sonographic appearance other than a complex cyst and a normal serum
      CA 125 level. During the period May 1988 to June 1993, 55 women fulfilled the
      criteria and underwent operative laparoscopy. During the same period, 75
      postmenopausal women underwent exploratory laparotomy for an adnexal cystic mass
      that was complex in appearance or associated with elevated serum CA 125. RESULTS:
      Laparoscopic bilateral oophorectomy was performed in all 55 women. All had benign
      masses (positive predictive value 100%). Malignant tumors were found in 23 of the
      75 women undergoing laparotomy (negative predictive value 30.7%). There was no
      significant difference in size of the tumors between women undergoing laparoscopy
      or laparotomy. CONCLUSION: Because of its safety and efficacy, laparoscopic
      management is the preferred procedure in postmenopausal women with a non-complex
      adnexal mass and a normal CA 125 level.

PMID- 8134072
TI  - Laparoscopic staging of the patient with incompletely staged early adenocarcinoma
      of the endometrium.
AB  - OBJECTIVE: To determine the feasibility of laparoscopic staging in patients with
      presumed early stage but incompletely surgically staged adenocarcinoma of the
      endometrium. METHODS: Thirteen patients with incompletely staged adenocarcinoma
      of the endometrium underwent laparoscopic staging. The women ranged in age from
      36-74 years (mean age 64) and weighed 132-201 lb (mean 147.5). The interval
      between hysterectomy and laparoscopic staging ranged from 14-63 days, for an
      average of 47. All patients underwent inspection of the entire intraperitoneal
      cavity, procurement of pelvic washings, and/or pelvic or para-aortic
      lymphadenectomy, and two patients had remaining ovaries removed. RESULTS:
      Extrauterine disease was found in three patients: One had intraperitoneal
      washings positive for adenocarcinoma, and two had pelvic lymph nodes positive for
      microscopic carcinoma. The average number of lymph nodes removed was 17.5. There
      were no intraoperative complications. Estimated blood loss averaged less than 50
      mL, and the mean hospital stay was 1.5 days. CONCLUSION: Our initial experience
      indicates that this is a safe, effective procedure that offers a short hospital
      stay. We consider laparoscopic staging an attractive option for some patients
      with incompletely staged early adenocarcinoma of the endometrium.

PMID- 8134073
TI  - Ondansetron and metoclopramide fail to prevent vomiting secondary to ultra-high
      dose cisplatin-carboplatin chemotherapy.
AB  - OBJECTIVE: To determine the severity of emesis caused by ultra-high-dose
      cisplatin-carboplatin chemotherapy and to compare the antiemetic efficacy of an
      ondansetron regimen and a metoclopramide regimen. METHODS: Forty consecutive
      patients with stage III or IV epithelial ovarian cancer or advanced or recurrent
      endometrial cancer were treated with ultra-high-dose cisplatin-carboplatin
      chemotherapy. No patient had received prior chemotherapy. Chemotherapy consisted
      of intravenous (IV) cisplatin 70 mg/m2 and IV carboplatin 100 mg/m2 administered
      on days 1 and 8 every 28 days for five cycles, representing a total monthly
      organoplatin dose of 207 mg/m2. Patients were randomized to receive
      metoclopramide, diphenhydramine, prochlorperazine, and lorazepam; or ondansetron,
      dexamethasone, prochlorperazine, and lorazepam. Patients were blinded and there
      was no crossover. The metoclopramide dose was 2 mg/kg IV every 2 hours x 3, and
      the ondansetron dose was 0.15 mg/kg IV every 4 hours x 3. RESULTS: All 40
      patients developed vomiting; 21 (52%) developed severe vomiting and seven (17%)
      required home IV therapy (grade 4). Eight patients (40%) receiving the
      metoclopramide regimen developed severe vomiting, compared to 13 (65%) in the
      ondansetron group (P = .50). Two patients (10%) in the metoclopramide group
      developed grade 4 vomiting, compared to five (25%) in the ondansetron group (P =
      .45). Except for sedation and amnesia, there were no significant side effects
      associated with either regimen. CONCLUSION: Neither regimen was effective in
      preventing high-dose cisplatin-carboplatin-induced emesis, and the ondansetron
      regimen did not appear to be superior.

PMID- 8134074
TI  - Germ cell tumors of the ovary arising after dermoid cyst resection: a long-term
      follow-up study.
AB  - OBJECTIVE: To study the long-term ovarian neoplastic consequences of resection of
      a dermoid cyst. METHODS: The study population comprised 99 patients who were
      operated on for an ovarian dermoid cyst. Follow-up information was obtained for
      91 women for a mean period of 5.06 +/- 2.46 years. RESULTS: Of the 99 women, 18
      had bilateral dermoid cysts. Multiple dermoid cysts in a single ovary were found
      in nine of the women with bilateral cysts and in one of the remaining patients.
      Two patients developed malignant germ cell tumors, and three developed a
      recurrent dermoid cyst in an ovary from which a dermoid cyst had previously been
      extracted. Bilateral or multiple ovarian dermoid cysts were present at the
      initial operation in four (80%) of these patients. CONCLUSIONS: Women with
      bilateral or multiple dermoid cysts may include a subgroup of patients with a
      greater tendency to develop future ovarian germ cell neoplasms.

PMID- 8134075
TI  - The predictive value of umbilical artery Doppler studies for preeclampsia or
      fetal growth retardation in a preeclampsia prevention trial.
AB  - OBJECTIVE: To determine the clinical utility of longitudinal Doppler umbilical
      artery systolic-diastolic ratios (S/D) to predict the occurrence of either
      preeclampsia or fetal growth retardation (FGR) in a low-risk population. METHODS:
      Healthy nulliparas with singleton gestations were enrolled in a double-blind
      trial of low-dose (60 mg) aspirin for preeclampsia prevention. Treatment was
      initiated at 24 weeks and continued until delivery. Continuous-wave Doppler
      studies were scheduled before assignment to treatment and at 27-31, 32-36, and 37
      42 weeks. Preeclampsia was defined as a persistent diastolic blood pressure of at
      least 90 mmHg with proteinuria, and FGR was defined as birth weight below the
      tenth percentile. Doppler values were considered abnormal if they exceeded the
      90th percentile for the gestational age range in the study population. Summary
      predictive values were computed for the abnormal S/D at each gestational age
      interval. To assess the potential effect of the administration of low-dose
      aspirin, logistic regression was used to model the relation between the Doppler
      indices, aspirin use, and these abnormal pregnancy outcomes. RESULTS: A total of
      1665 Doppler examinations were performed on 565 women. Forty-four fetuses
      developed FGR and 21 women were diagnosed with preeclampsia. The positive
      predictive values of an abnormal S/D for the subsequent development of FGR were
      13-17% across the gestational age ranges studied, and the positive predictive
      values for preeclampsia were 0-5%. Aspirin treatment did not affect the relation
      between the Doppler indices and these outcomes in the logistic regression model.
      CONCLUSION: Elevated umbilical artery S/D is not a clinically useful predictor of
      either FGR or preeclampsia in a low-risk population.

PMID- 8134076
TI  - Estrogen mediates the pregnancy-enhanced cardiotoxicity of cocaine in the
      isolated perfused rat heart.
AB  - OBJECTIVE: To determine whether pregnancy enhances cocaine toxicity in the
      isolated perfused whole rat heart model and whether this enhanced toxicity can be
      simulated by pre-treatment with either estrogen or progesterone. METHODS: Hearts
      excised from 65 female Sprague-Dawley rats were attached to a Langendorff
      apparatus for measurement of left ventricular systolic pressure, heart rate, and
      contractility. Before excision, the animals were assigned to one of five groups:
      1) nonpregnant, 2) pregnant, 3) nonpregnant pretreated with progesterone, 4)
      nonpregnant pretreated with estrogen, and 5) nonpregnant pretreated with estrogen
      and progesterone. Each group was exposed serially to the following cocaine
      concentrations: 5 x 10(-6), 1 x 10(-5), and 6 x 10(-5) mol/L. RESULTS: Heart rate
      declined at all doses of cocaine (9.2, 6.9, and 31.0%, respectively). The lowest
      dose of cocaine had positive inotropic effects, with a 23.2% increase in left
      ventricular pressure and a 15.3% increase in contractility. Exposure to the two
      higher doses resulted in negative inotropic effects (a 24.8% decrease in left
      ventricular pressure and a 39.7% decrease in contractility for the highest dose).
      Although pre-treatment with estrogen, alone or with progesterone, resulted in
      responses similar to those seen in pregnant animals, progesterone pre-treatment
      alone failed to do so. CONCLUSIONS: Cocaine displayed cardiotoxicity in isolated
      rat hearts similar to that in other animal models. This toxicity was enhanced by
      pregnancy. We were able to simulate changes by pretreating the animals with
      estrogen. Perhaps the enhanced cardiotoxicity of cocaine in pregnancy is
      partially mediated by estrogen.

PMID- 8134077
TI  - Nifedipine and its indications in obstetrics and gynecology.
AB  - OBJECTIVE: To review studies and investigations regarding the safety and efficacy
      of nifedipine. DATA SOURCES AND METHODS: We reviewed the published literature on
      calcium channel blockers and their pharmacology and therapeutic applications in
      obstetrics and gynecology. We paid particular attention to methods of animal
      research and recent clinical evaluations. CONCLUSIONS: The dihydropyridine group
      of calcium channel blockers (type II calcium blockers) and, specifically,
      nifedipine are safe for use in pregnancy. They have little teratogenic or
      fetotoxic potential. Nifedipine's mechanism of action is through smooth-muscle
      relaxation secondary to blockage of the slow calcium channels into the cells. In
      vivo, there is minimal effect on the cardiac conducting system. Multiple studies
      in women have demonstrated the effectiveness and safety of nifedipine as an
      antihypertensive. Therapeutic doses range from 10-30 mg orally every 6-8 hours.
      For acute control of hypertension, 10 mg of sublingual nifedipine may be used.
      Nifedipine is as effective as beta-mimetics in decreasing uterine activity. As a
      tocolytic agent, it is more effective as there are fewer patients who have to
      discontinue nifedipine because of side effects. The side effects of nifedipine
      include flushing, headache, or, rarely, hypotension in the hypovolemic patient.
      Nifedipine has potential and theoretical indications for dysmenorrhea and bladder
      irritability.

PMID- 8134078
TI  - Does cesarean delivery prevent cerebral palsy or other neurologic problems of
      childhood?
AB  - OBJECTIVE: To determine whether cesarean delivery can lead to fewer childhood
      neurologic problems. DATA SOURCES: We reviewed English language articles
      published between 1969 and 1993, obtained via MEDLINE search of the heading
      "delivery, abdominal." Bibliographies of book chapters and articles about
      cerebral palsy and other childhood neurologic disorders were also searched.
      METHODS OF STUDY SELECTION: We sought articles that dealt with vaginal versus
      cesarean delivery and the following outcomes: cerebral palsy, abnormal neurologic
      development, neonatal seizures, and neonatal intraventricular hemorrhage. Ten
      relevant studies were identified, only four of which were prospective, and only
      one of which (involving breech births) was a randomized trial. DATA EXTRACTION
      AND SYNTHESIS: No study found a significant difference in the rates of cerebral
      palsy, abnormal neurologic development, and neonatal seizures between those
      children born vaginally or by cesarean. The severity of handicap of infants born
      with myelomeningocele was less in those delivered via cesarean. Infants born by
      cesarean had a decreased risk for developing neonatal brachial plexus palsy.
      Cesarean delivery of mothers with human immunodeficiency virus (HIV) or with
      genital lesions and no history of herpes may benefit the infant. CONCLUSIONS:
      Cesarean delivery can reduce the risk of adverse childhood neurologic outcome for
      those born with myelomeningocele, and may reduce the rate of brachial plexus
      palsies and neonatal herpes and HIV infections. However, children born by
      cesarean have no documented reduced risk of other childhood neurologic problems
      or cerebral palsy.

PMID- 8134079
TI  - A survey of practices in infectious diseases by obstetrician-gynecologists.
AB  - OBJECTIVE: To survey current practices among obstetricians and gynecologists
      concerning a wide range of infectious diseases to guide future efforts in
      continuing medical education. METHODS: A survey questionnaire of multiple-choice
      questions was mailed to 2500 physicians, under age 65, randomly selected from the
      American Medical Association specialty list of obstetrician-gynecologists. The
      first 500 returns constituted the data set and were analyzed by computer.
      RESULTS: We found many clinical areas in which practice patterns were deemed
      appropriate, including antibiotic selection, universal screening for hepatitis B,
      and follow-up of urinary tract infection in pregnancy. In other areas, marked by
      controversy among "experts," practice patterns varied widely. These areas
      included management of premature rupture of the membranes and premature labor,
      and universal screening for group B streptococci. Areas in need of further
      continuing medical education efforts include management of perinatal viral
      infections and diagnosis and treatment of sexually transmitted diseases.
      CONCLUSIONS: Although this survey indicated that practice patterns of American
      obstetricians and gynecologists are appropriate in many clinical areas relevant
      to infectious diseases, there are other clinical conditions requiring future
      efforts in continuing medical education.

PMID- 8134080
TI  - Immunization as therapy for recurrent spontaneous abortion: a review and meta
      analysis.

PMID- 8134081
TI  - Asthma in pregnancy.

PMID- 8134082
TI  - An ethical justification for emergency, coerced cesarean delivery.

PMID- 8134083
TI  - An ethical justification for emergency, coerced cesarean delivery.

PMID- 8134084
TI  - Alpha- and gamma-interferon inhibit plasminogen activator inhibitor-1 gene
      expression in human retinal pigment epithelial cells.
AB  - The effect of interferons IFN-alpha and IFN-gamma on the production of
      plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs) was
      examined in human retinal pigment epithelial (RPE) cells in culture. Cultures of
      human RPE cells were incubated with either of the interferons for 48-96 h. The
      cell cultures were assayed using mRNA analysis and solid-phase immunocapture
      assay. Both interferons caused a marked decrease in PAI-1 mRNA expression after
      48 h with no change in urokinase-type plasminogen activator (u-PA) mRNA
      expression. A marked decrease in PAI-1 activity and concomitant increase in u-PA
      activity in the culture medium appeared only after 72-96 h. We conclude that IFN
      alpha and IFN-gamma stimulate plasminogen-mediated pericellular proteolysis of
      human RPE cells in culture by inhibiting PAI-1 gene expression.

PMID- 8134085
TI  - Low-molecular-weight peptides in corneal tissue culture media and in bovine
      aqueous fluid.
AB  - Eight putative, low-molecular-weight peptides have been found in the media of
      bovine corneal tissue cocultures and in bovine aqueous fluid. By investigating
      amine fluid extracts from these sources by HPLC, possible amino acids, vitamins
      and urea were eliminated as the unknown peaks of interest. The molecular weights
      of these substances were equal to or less than 1,000 D. The peaks did not
      correspond to glutathione or bradykinin either which fall in this molecular
      weight range. As the cultures aged from 10 to 32 days, it was found that 5 of the
      8 peptides varied in concentration. Five peptides increased in concentration to
      day 17 and slowly decreased afterwards. Efforts are not directed toward the
      identification of these peptides.

PMID- 8134086
TI  - Media conditioned by coculture of pericytes and endothelial cells under a hypoxic
      state stimulate in vitro angiogenesis.
AB  - We investigated the role of pericytes in retinal neovascularization and the
      effect of hypoxia on it. Conditioned media (CM) were harvested from cultured
      pericytes, retinal capillary endothelial cells (RCEs) or cocultured pericytes and
      RCEs at 1, 5 and 20% O2. The effect of these CM on the capillary-like tube
      formation of RCEs in the collagen gel was then investigated. The CM harvested
      from either pericytes or coculture of pericytes and RCEs in a hypoxic environment
      (1 and 5% O2) significantly enhanced the tube formation of RCEs (p < 0.01), while
      the CM of coculture at 20% O2 showed an inhibitory effect (p < 0.01). The present
      study suggests that pericytes release angiogenic factors under hypoxic
      conditions, i.e. at 1 and 5% O2, while they release angiostatic factors when they
      are cocultured with RCEs at 20% O2.

PMID- 8134087
TI  - Refractive index of the human lens surface measured with an optic fibre sensor.
AB  - The refractive index of the human eye lens has been measured directly with a
      reflectometric, optic fibre sensor. Thirteen human lenses ranging in age from 27
      to 84 years were examined. The results show that the refractive index is higher
      on the anterior than on the posterior surface with most of the values ranging
      from 1.364 to 1.381 and 1.338 to 1.357, respectively. There is no topographical
      variation along either surface and no evidence of age-related differences.
      Results using the sensor are compared with those from the Abbe refractometer on
      homogeneous materials. The refractive index of distilled water was found to be
      1.332 with the fibre sensor and 1.3326 with the Abbe refractometer; of 0.5%
      agarose gel, it was 1.334 and 1.3355, respectively.

PMID- 8134088
TI  - Reactive oxygen species involved in phenazine-methosulfate-induced rat lens
      opacification. An experimental model of cataract.
AB  - The excised rat crystalline lens opacified when incubated aerobically with
      phenazine methosulfate, but no opacification was observed under anaerobic
      conditions. Morphological studies revealed development of opacification in the
      cortex. The opacification resembled that often seen in the early period of senile
      cataract as well as in naphthalene-induced and UV cataract. Both an increase in
      hydration and in electrolyte imbalance accompanied this opacification. Na,K
      ATPase activity of the opacified lens was found to decrease. In order to
      investigate if activated oxygen is involved in these processes, we conducted an
      electron spin resonance study by means of a spin trapping technique. When the
      lens homogate was incubated with phenazine methosulfate, OH radicals were
      generated under aerobic but not under anaerobic conditions. Reduced pyridine
      nucleotides must be involved in the process, because the mixture of nicotinamide
      adenine dinucleotide phosphate [NAD(P)] and phenazine methosulfate did not
      generate OH radicals, but the mixture of NAD(P)H and phenazine methosulfate
      generates OH radicals, indicating that reduced phenazine methosulfate was
      involved in the OH radical generation. Probably, the generated OH radicals
      inactivated Na,K-ATPase residing in the epithelium of the lens, which eventually
      caused opacification of the lens. The present experiment system may be used for
      the elucidation of lens opacification (cataract) involved with reactive oxygen
      species.

PMID- 8134089
TI  - Molecular mechanisms of photochemically induced posterior vitreous detachment.
AB  - Vitreous gel contraction and syneresis, commonly associated with age- and disease
      related posterior vitreous detachment (PVD), were induced by a hematoporphyrin
      (HP)-photosensitized reaction. Calf vitreous gel was irradiated by white light in
      the presence of HP. Gel weights of the vitreous samples after 24 h of irradiation
      decreased by 14%, the irradiated control without HP by 8% and the control with HP
      stored in the dark by 8%. No significant difference in vitreous gel
      compressibility was found between the irradiated controls and the irradiated
      samples. In separate experiments, collagen gel in a glass capillary and
      hyaluronic acid (HA) were irradiated with white light in the presence of HP. The
      control collagen gel (irradiated without HP and stored in the dark with HP)
      decreased in length by 0.6% after 96 h, the experimental gel with HP decreased in
      length by 1.3 and 1.9% after 24- and 96-hour irradiation by visible light,
      respectively. The irradiated HA monitored by high-performance liquid
      chromatography showed a molecular weight decrease in the HP-treated polymer.
      Because the HP-sensitized reaction predominantly produces singlet oxygen,
      collagen gel contraction and HA degradation, in this case, are likely caused by
      this active oxygen species.

PMID- 8134090
TI  - Correlation of phospholipid hydroperoxide glutathione peroxidase activity to the
      sensitivity of rat retinas to photic injury.
AB  - We hypothesize that the differential susceptibility to photic injury among
      different strains of rat retinas may depend on the levels of phospholipid
      hydroperoxide glutathione peroxidase (PHGPX) activity, one of the endogenous
      antioxidant enzymes in the retina. The retinas of four inbred strains of albino
      rat (Fischer, Wistar, Buffalo and Lewis) were analyzed for glutathione peroxidase
      activity using H2O2, cumene hydroperoxide, and phospholipid hydroperoxide as
      assay substrates. In all four strains of rat, PHGPX was observed only in the high
      salt extract of the retina, while peroxidases determined by H2O2 or cumene
      hydroperoxide were observed mainly in the low salt extract. PHGPX was highest
      (66.7 mU/mg) in the most light-resistant Fischer strain and lowest in the most
      light-sensitive Lewis strain (31.9 mU/mg), while the activity levels in the
      moderately light-sensitive Buffalo and Wistar strains were 46.6 and 38.5 mU/mg,
      respectively. In contrast, there was no significant difference in peroxidases
      determined by H2O2 or cumene hydroperoxide among the four strains. These
      observations suggested that, in rat retina, the membrane-associated PHGPX may
      have an important role in the defense against light-induced free radical damage.

PMID- 8134091
TI  - [Preoperative assessment of geriatric patients for emergency and for elective
      procedures].
AB  - The altered physiology of the older patient in combination with the increased
      number of disease processes increases the potential risk of perioperative
      complications. The usual diagnostic procedures often fail to uncover the multiple
      problems these patients have. They need a comprehensive preoperative assessment,
      which includes a thorough history, physical examination and laboratory testing.
      Special considerations include an evaluation of the nutritional status, the
      functional capabilities and an assessment of the patients' cognitive and
      emotional status. This type of comprehensive assessment helps the physician to
      minimize the perioperative risks for older patients and is an excellent tool for
      improving the postoperative care and rehabilitation procedures.

PMID- 8134092
TI  - [Surgical risk and anesthesia in geriatric patients].
AB  - The percentage of elderly people in our population is increasing, and
      anaesthesiologists and surgeons need to find ways of decreasing perioperative
      complications in these patients. The chronological age is of lesser importance
      than biological age as far as the risks of perioperative complications are
      concerned. Indicators for biological age are the number and type of previous
      diseases, nutritional status and the doctor's clinical impression of the patient.
      Preoperative evaluation of the perioperative risks in elderly patients is now
      mandatory. The physical status classification of the American Society of
      Anesthesiologists and the Goldmann Index are very useful for patient evaluation.
      Optimal preparation of the patient is helpful in decreasing risks, and the
      avoidance of emergency operations will also decrease risks. It is not yet clear
      whether regional anaesthesia, as opposed to general anaesthesia, decreases
      mortality in geriatric patients. It seems, however, that regional anaesthesia may
      have some advantages in terms of postoperative consciousness, blood loss,
      thrombotic complications and mean length of stay in hospital. The surgeon can
      help reduce the operative risk by a rapid and atraumatic operation technique. The
      most frequent perioperative complications are alterations to the cardiopulmonary
      system and postoperative bleeding. Even minor perioperative complications can
      have a predictive value for later fatal events. Thus, careful preoperative
      preparation, a suitable anaesthetic procedure and a fast and atraumatic mode of
      operation will help to decrease perioperative complications in elderly patients.

PMID- 8134093
TI  - [Walking ability and independence in old age].
AB  - Physiological changes associated with aging and their influence on the activities
      of daily living (ADL) in old and very old persons are discussed. Degenerative
      diseases of the spine and of weight-bearing joints may affect the ability to walk
      and may thus endanger independent living. Treatment of orthopedic disease in the
      elderly should include efforts at rehabilitation aimed at enabling the patient to
      return home. For this, patients should be able to walk, or if this goal seems to
      be inaccessible, independence in ADL should be aimed for. Special aspects of
      rehabilitation are discussed for old patients following hip replacement or lower
      leg amputation.

PMID- 8134094
TI  - [Epidemiology and treatment of fractures in old age].
AB  - The frequency of fractures in the elderly has risen dramatically and will
      increase further in the future. This is partly a socio-economic problem and is
      familiar both to surgeons and to the general population. Fractures in such
      patients have clinical and pathomechanical implications, with unassociated
      conditions needing treatment. It is necessary to standardize treatment, including
      operative procedures, which can be performed in every hospital. The therapeutic
      measures available involve close cooperation between the surgeon, the
      geriatrician and ancillary workers. For some fractures in the elderly there are
      already operative procedures that ensure efficient rehabilitation and
      reintegration into society. Osteoporosis can make osteosynthesis problematic.
      Radiological measurements of bone density are of diagnostic rather than
      therapeutic value. Operative procedures and their effectiveness in common
      fractures in the elderly (hip, distal radius, shoulder) are discussed. It is
      stated that surgical treatment is very important in mastering this challenge, but
      other aspects, particularly ethical considerations, are paramount.

PMID- 8134095
TI  - [Extra-articular pathogenetic factors in arthritis and deformities in old age as
      exemplified by varus gonarthrosis].
AB  - Extraarticular, predominantly neuromuscular, factors are thought to contribute to
      the development of osteoarthritis. With increasing age, changed temporal dynamics
      of motor reflexes and reduced muscular force may affect the efficacy of
      neuromuscular protection of the knee joint. In three experimental studies
      conducted with osteoarthritis patients and healthy controls, no difference was
      found in monosynaptic reflex times and latencies of somatosensory evoked brain
      potentials. Muscular force was generally diminished in the patients, with the
      most prominent reduction during coxal abduction. Osteoarthritis patients had
      marked nociceptive hyposensitivity, but no difference was seen in fast conduction
      afferent systems. In an animal study with high locomotion load, interruption of
      articular afferent nerve fibers led to a precipitation of cartilage degeneration.
      It is concluded that minor extraarticular functional deficits acting over time,
      probably support and aggravate the development of osteoarthritic changes.

PMID- 8134096
TI  - [Bone density measurements and their indications].
AB  - Today the following two methods of measuring the bone mineral density (BMD) are
      widely used: dual-photon absorptiometry with X-rays (DEXA) and quantitative
      computed tomography (qCT). DEXA measures the BMD of the vertebral column, the
      femur and the whole skeleton, qCT the vertebral column and the radius and tibia.
      The qCT method permits a distinction to be made between trabecular and cortical
      bone, which offers an advantage in terms of the choice of treatment because
      cortical and trabecular bone do not change in parallel. For example, fluorides
      are contraindicated when cortical bone is diminished. There are important
      differences among the methods of densitometry concerning reproducibility. The
      highly sensitive method of peripheral qCT (Densiscan) has an overall
      reproducibility of 0.3% (mixed population), allowing a change in BMD of less than
      1% to be detected. This enables us to adapt quickly the treatment according to
      the stage and progression of the disease. In the perimenopausal patient, bone
      mineral densitometry is indicated to detect high-risk patients; in the
      postmenopause patient, densitometry should be performed in order to "tailor" the
      treatment of osteoporosis. Patients with a "slow loser" osteoporosis are
      preferably treated with bone-simulating substances (e.g., fluorides, ossein
      hydroxyapatite compound), patients with a "fast loser" osteoporosis (trabecular
      bone loss, measured at the distal radius, of more than 3.5% per year) with anti
      resorption agents such as estrogens, bisphosphonates, calcitonin and anabolic
      steroids. This tailored treatment reduces not only the number of non-responders,
      but improves patient compliance because it allows the choice, duration or change
      of the treatment to be substantiated by means of hard data.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8134097
TI  - [Surgical treatment of the degenerative lumbar spine in ild age].
AB  - Degenerative lumbar spine conditions, mostly combinations of spinal stenosis,
      instability, deformity and arthrosis, threaten the independence of elderly
      patients due to intractable pain and loss of function. Comprehensive operative
      treatment is possible, but is often not offered to these patients. The reasons
      are: fear of an unsuccessful outcome, fear of fatal complications and
      underestimation of the remaining life span. The literature shows that good
      results can be obtained in approximately 80% as well in one- and two-level
      degenerations as in multisegmental deformities. Perioperative mortality is about
      zero, but the the costs are high, approximately twice as much as for a total hip
      replacement. The single most frequent complication in 50 patients over 70 years
      was temporary cerebral problems. With adequate precautions the gain in quality of
      life outweighs the risks and costs.

PMID- 8134098
TI  - [Elective total hip prosthesis management in patients over 80 years of age].
AB  - Ninety-five primary elective total hip prosthesis procedures were carried out in
      patients over 80 years of age (average 82.9 years). The results were studied
      retrospectively to determine the individual risk-advantage relationship and the
      general cost-advantage relationship taking the social aspects into consideration.
      Fractures and emergency procedures were excluded. Ninety-three percent of the
      patients had preexisting general illnesses. There were no local or general
      complications in the peri- and postoperative courses of 86% and 85%,
      respectively. The general complications included urological (6%), cardiovascular
      (5%) and abdominal (3%) problems. The only death (myocardial infarction) took
      place 4 weeks after the operation during the rehabilitation phase. The average
      hospital stay was 23.3 days; 20% of the patients were then able to return home,
      while 80% were sent to another institution for further care (geriatric
      department, rehabilitation), where the average stay was 36.7 days. The total
      inpatient treatment period was on average 52.3 days. At the time of the last
      follow-up, an average of 4.6 years postoperatively, 75% of the patients were
      alive with an average age of 87.4 years. Seventy-nine percent were still able to
      live alone and look after themselves; 81% were independent or only partially
      dependent (living in a retirement home). Ninety-three percent had no pain or only
      mild pain. If indicated, the operation risk factor for total hip prostheses in
      patients over 80 years is obviously low, and the results are good. This operation
      permits the patient to have many years free of pain, to remain independent, and
      to achieve a clearly higher quality of life. In this way one can also save on the
      high cost of many years of nursing care.

PMID- 8134099
TI  - [Gait changes in elderly people].
AB  - Age-associated changes in gait produce a decrease in walking velocity,
      predominantly caused by a reduction in the length of the step and to a lesser
      degree in cadence. The length of the step becomes shorter because of impaired
      balance, diminished muscle strength and muscle contractures that decrease the
      joint range of motion. Impairment of the quality of their gait is a major risk
      factor for falls in the elderly with subsequent minor or major injuries. Age
      related changes in gait of elderly people must be taken into account when
      planning orthopedic surgical procedures and applying orthopedic devices such as
      orthoses and lower extremity prostheses. Exercise programs to maintain and
      improve muscle strength, equilibrium reactions as well as neuromotor coordination
      have proved effective in postponing and correcting age-related gait instability
      and in increasing walking velocity as well as mobility in daily life.

PMID- 8134100
TI  - [Rehabilitation of the geriatric patient].
AB  - As the twentieth century draws to a close, people in the western industrialized
      countries have a longer life expectancy. As more people live longer, the
      proportion of the population that is handicapped and susceptible to chronic
      diseases is also increasing. Geriatrics has become an accepted medical specialty
      concerned with the very old. It seeks, through general and targeted measures, to
      enhance the lives of these handicapped people and enable them to be more
      independent. This is best done in a modern geriatric clinic with an attached day
      care clinic. Only when an experienced multidisciplinary team basing its work on
      careful geriatric assessment determines the rehabilitation goal, evaluates the
      potential, and implements a definite programme can the maximum success be
      anticipated. Specialized orthopaedic-geriatric units working together can achieve
      the most satisfactory results for effective rehabilitation of elderly patients
      after orthopaedic surgery.

PMID- 8134101
TI  - [Muscle strength training in old age].
AB  - Muscle strength decreases with increasing age. The main causes for this are
      intrinsic age-dependent mechanisms and hypokinesia. Immobilization and bed rest
      accelerate the loss of muscle strength. A number of studies show that even very
      old people can increase their strength, sometimes to a surprising degree. Thus,
      there is considerable potential for strength training in the rehabilitation of
      the elderly. Adaptation to strength training, the methods for improving strength
      and the importance of health problems related to strength training are discussed.
      If carefully planned and supervised, strength training is feasible even in people
      with chronic diseases like mild hypertension, coronary heart disease and
      osteoarthritis; actually, strength training may even be beneficial. Also,
      strength training becomes increasingly important in rehabilitation after
      orthopedic surgery.

PMID- 8134102
TI  - [Amputation in geriatric patients].
AB  - The incidence of amputation rises dramatically in old age. Trauma and tumors are
      uncommon reasons in this age group, however; 90% of amputations in such patients
      are performed for occlusive disease. These patients are distinguished from all
      other amputees by their multiple morbidity, which must be borne in mind at all
      stages, from the decision to operate to rehabilitation. This paper briefly
      indicates the points that are important for an optimal result of rehabilitation,
      starting with selection of the amputation level and extending through to
      provision of the prosthesis and mobilization. The paper ends with a presentation
      and discussion of the results of rehabilitation in 90 patients aged over 70.

PMID- 8134103
TI  - Immunolocalization of the Nuk receptor tyrosine kinase suggests roles in
      segmental patterning of the brain and axonogenesis.
AB  - Neural kinase (Nuk) encodes a murine receptor-like tyrosine kinase belonging to
      the Eph/Elk/Eck family. Protein localization studies indicate that during early
      embryogenesis Nuk is confined to the developing nervous system, where it marks
      segments along the axis of the neural tube in the hindbrain (rhombomeres r2, r3
      and r5) and specific morphological bulges of the midbrain and forebrain.
      Subcellular localization of Nuk indicates that this receptor is concentrated at
      sites of cell-cell contact, often involving migrating neuronal cells or their
      extensions. Most notably, high levels of Nuk protein are found within initial
      axon outgrowths and associated nerve fibers. The axonal localization of Nuk is
      transient and is not detected after migrations have ceased, suggesting a role for
      this tyrosine kinase during the early pathfinding and/or fasciculation stages of
      axonogenesis. The subcellular localization of Nuk, as well as the presence of
      fibronectin type III and immunoglobulin-like adhesive domains on the
      extracellular region, suggest this receptor tyrosine kinase may function to
      regulate specific cell-cell interactions during early development of the murine
      nervous system.

PMID- 8134104
TI  - Evidence for retinoblastoma protein (RB) dependent and independent IFN-gamma
      responses: RB coordinately rescues IFN-gamma induction of MHC class II gene
      transcription in noninducible breast carcinoma cells.
AB  - The class II major histocompatibility (MHC) genes encode cell surface
      heterodimers that present processed antigen to CD4 positive T-cells. The class II
      genes are expressed constitutively on B-cells and can be induced by IFN-gamma on
      a variety of other cell types. Because the class II genes are aberrantly
      expressed on many mesenchymal tumors, which are frequently defective for the
      retinoblastoma tumor suppressor protein (RB), we investigated the role of RB in
      the regulation of HLA-DR and -DP. The RB defective breast carcinomas cell line,
      MDA-468-S4 (S4), as well as S4 subclones reconstituted with RB coding sequences
      under the control of a zinc inducible promoter, were treated with IFN-gamma and
      examined for DR and DP expression. Surface DR is not inducible in S4 cells, but
      inducibility is rescued by RB. DP is only slightly inducible in S4, but inducible
      to a much higher level in the RB positive subclones of S4. IFN-gamma induction of
      DR and DP mRNAs are correspondingly dependent on RB. IFN-gamma receptors are
      present on S4 cells, and the guanylate binding protein and ICAM-1 genes respond
      to IFN-gamma, ruling out the possibility that all IFN-gamma signal transduction
      pathways are defective in S4 cells. These data indicate RB regulates the
      coordinate response of class II genes to IFN-gamma. Possible roles for RB in this
      process are discussed, as well as the role of the class II-noninducible phenotype
      in tumor rejection.

PMID- 8134105
TI  - Heterozygous Rb-1 delta 20/+mice are predisposed to tumors of the pituitary gland
      with a nearly complete penetrance.
AB  - Humans with a germline mutation of the RB gene are predisposed to retinoblastoma
      with a 90% penetrance and are at higher risk for other rare tumors. We have
      established a mouse strain carrying a germ-line mutation of the Rb-1 gene. Here
      we describe a nearly 100% incidence of spontaneous pituitary tumors which arise
      in Rb-1 heterozygous mice from ages 2 to 11 months. Histological and
      immunological analysis indicate that these tumors originate from the intermediate
      lobe of the pituitary gland, which is a vestigial structure in adult humans.
      Progression of the tumors can be followed by the elevated level of a specific
      proteolytic product of pro-opiomelanocortin prohormone, alpha-melanocyte
      stimulating hormone, in the circulating blood of the tumor-bearing animals.
      Multiple foci are frequently seen in the tiny intermediate lobe of the pituitary
      gland which contains approximately 1.5 x 10(5) cells. The tumor tissues
      invariably lose expression of full-length Rb protein due to loss of the single
      wild-type Rb-1 allele. The Rb knock out mouse strain provides a unique model for
      addressing tissue-specific tumor predisposition by inactivation of a ubiquitously
      expressed tumor suppressor gene.

PMID- 8134106
TI  - Functional aspects of B-Myb in early Xenopus development.
AB  - The gene encoding Xenopus B-Myb (XB-Myb), a protein structurally related to the
      nuclear protooncogene product c-Myb, is expressed in early Xenopus embryogenesis.
      We report on developmental alterations in the nucleocytoplasmic distribution and
      phosphorylation of XB-Myb in Xenopus oocytes and embryos, as well as on a
      negative regulatory role of the carboxyl terminus in sequence specific DNA
      binding. In growing oocytes and early embryonic stages the protein is primarily
      located in the nucleus; in the full-grown oocyte, however, it remains sequestered
      in the cytoplasmic compartment. Upon meiotic maturation of the oocyte, XB-Myb
      becomes hyperphosphorylated. Oocyte/egg isolates of XB-Myb are inhibited in their
      specific DNA binding activity; truncation of the carboxyl terminal region
      relieves this block in nucleic acid recognition. Furthermore, we have used
      overexpression of XB-Myb in Xenopus embryos by means of mRNA injection as an
      assay for gene function in vivo. Overexpression of full-length XB-Myb, not of the
      carboxyl terminal deletion mutant, results in an altered morphology of lateral
      plate mesoderm.

PMID- 8134107
TI  - A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF
      9 nor ENL.
AB  - Most of the translocations affecting the chromosome band 11q23, frequently seen
      in human acute leukemias, involve a restricted area of the HRX gene. We have
      characterized two t(1;11)(p32;q11) translocations which fuse the HRX gene to a
      novel gene, AF-1p on chromosome 1p32, in two myeloid leukemias. The der (11)
      chromosome expresses the 1368 N-terminal amino acids of HRX, including the AT
      hook, snRNP and methyltransferase similarities, fused to almost all the AF-1p
      product. The predicted wild type AF-1p product is a 98 kDa acidic protein which
      does not exhibit similarity to the AF-4, AF-9 and ENL gene products. It is highly
      similar to the murine eps 15 gene product, which encodes a cytoplasmic
      phosphoprotein. Our data indicate that AF-1p defines another class of genes fused
      to HRX in 11q23 abnormalities.

PMID- 8134108
TI  - Bifunctional transcriptional properties of YY1 in regulating muscle actin and c
      myc gene expression during myogenesis.
AB  - Oncogene expression is generally incompatible with terminal cell differentiation
      as in myogenesis. We present evidence that this incompatibility can be caused in
      part by the dual activity of a Kruppel-related zinc finger, YY1 (formerly F
      ACT1), in differentially regulating oncogene and muscle-specific gene expression.
      The c-myc and skeletal alpha-actin gene promoters contain YY1 binding sites
      thought to act either as positive or negative cis-acting elements. Through
      manipulating the intracellular level of YY1 by treating primary myoblasts with
      bromodeoxyuridine (BrdU), which inhibited myogenesis and increased the YY1
      protein content, or by transfecting YY1 cDNA expression vector, we show that it
      can simultaneously inhibit and activate expression of the skeletal alpha-actin
      and c-myc genes, respectively. The transrepression activity of YY1 solely depends
      on its C-terminal zinc finger region (amino acids 297-407) while its
      transactivation function requires an additional N-terminal domain (amino acids 1
      90) normally masked in the full-length protein. We propose that the high level of
      YY1 in proliferating myoblasts might serve to maintain c-myc expression and
      suppress muscle actin expression, which can then be gradually reversed by
      downregulating YY1 activity toward myogenesis.

PMID- 8134109
TI  - Expression cDNA cloning of a novel oncogene with sequence similarity to
      regulators of small GTP-binding proteins.
AB  - We generated a cDNA expression library from a human mammary epithelial cell line
      for detection of novel oncogenes by focus formation assay in NIH3T3 cells. A
      morphologically unique focus was identified and the transforming plasmid was
      isolated. The transforming gene, designated TIM, encoded a predicted protein
      species of 60 kDa containing a Dbl-Homology (DH) motif. This motif is also
      present in other growth regulatory molecules including Bcr, Cdc24, Vav, Ras-grf,
      and Ect2 which have been implicated as regulators of small GTP-binding proteins.
      NIH3T3 cells transfected with TIM expression plasmid showed altered growth
      properties in vitro and were tumorigenic when injected into nude mice. The 6.5
      kilobasepair (kb) transcript of the TIM gene was mainly expressed in kidney,
      liver, pancreas, lung, and placenta. By analysing a panel of human-hamster
      somatic cell hybrids, we localized the TIM gene to human chromosome 7.

PMID- 8134110
TI  - c-fos and c-jun overexpression in malignant cells reduces their tumorigenic and
      metastatic potential, and affects their MHC class I gene expression.
AB  - Reduced co-expression of the c-fos and c-jun protooncogenes has been correlated
      with the down regulation of H-2K class I major histocompatibility antigens in
      high-metastatic cell lines from the Lewis lung carcinoma, B16 melanoma and the
      K1735 melanoma. Transfection of c-jun and c-fos genes into the high metastatic
      clones D122 (3LL) and F10.9 (B16 melanoma) resulted in activation of H-2 class I
      gene expression. D122 transfectants expressing high levels of c-jun and c-fos and
      F10.9 transfectants expressing high levels of c-fos exhibited markedly reduced
      tumorigenicity and were of low metastatic potential. In contrast, transfection of
      junB into the low metastatic, high H-2Kb, Db expressor clone A9 (3LL), reduced
      MHC class I gene expression, and converted the parental low, into high-metastatic
      cells. The data demonstrate the involvement of genes from the fos and jun family
      in regulation of MHC class I expression and consequently in regulation of
      immunogenicity and metastatic competence of tumor cells.

PMID- 8134112
TI  - Creation of an hepatocyte growth factor/scatter factor autocrine loop in
      carcinoma cells induces invasive properties associated with increased
      tumorigenicity.
AB  - Exogenous HGF/SF converts subconfluent cultures of NBT-II epithelial carcinoma
      cells into mobile fibroblast-like cells while being only mitogenic for cells
      maintained at high density. To investigate the potential role of such factor in
      tumor progression, we generated HGF/SF-producing NBT-II cells by transfection
      with an expression plasmid containing human HGF/SF cDNA. HGF/SF-producing cells
      also exhibit a fibroblastic phenotype. Media conditioned by these cells are
      potent inducers of in vitro tubulogenesis which can be inhibited with specific
      anti-HGF/SF antibodies; these antibodies are also able to reverse the scattered
      phenotype of the HGF/SF-producing cells. In addition spheroids of HGF/SF
      producing cells are dispersed into 3D collagen gels suggesting an increase of
      invasive properties of these cells. When injected in nude mice, these HGF/SF
      producing cells induce tumors appearing more rapidly than did those obtained with
      untransfected cells. These results show that HGF/SF can promote motility and
      invasive properties of NBT-II bladder carcinoma cells and also confers a
      tumorigenic advantage when acting as an autocrine factor.

PMID- 8134111
TI  - Unliganded c-erbA/thyroid hormone receptor induces trkB expression in
      neuroblastoma cells.
AB  - Neurotrophins are responsible for the differentiation and survival of neurons in
      the developing and in the adult nervous system. They bind to specific membrane
      receptors with tyrosine kinase activity whose prototype is the product of the
      trkA proto-oncogene. TrkB, a member of this family, is the receptor for the
      neurotrophins brain derived growth factor (BDNF) and neurotrophins-3, -4/5. In
      this study, we show that stable expression of the c-erbA proto-oncogene, which
      encodes the alpha 1-isoform of the nuclear receptor for thyroid hormone (Tr alpha
      1) induces the expression of trkB mRNA with a concomitant decrease to
      undetectable levels of trkA and trkC mRNAs in the mouse neuroblastoma N2a cell
      line. trkB induction by c-erbA is ligand independent, since addition of T3 had no
      effect. The induced trkB transcript encodes a functional gp145trkB protein, which
      is phosphorylated on tyrosine in response to BDNF. Furthermore, induction of trkB
      mRNA is also caused by transient expression of either TR alpha 1 or beta 1
      isoforms. Our results are compatible with the idea that there are certain
      pathways which are under control of unliganded thyroid hormone receptor, and that
      one of these pathways results in regulation of trk expression.

PMID- 8134113
TI  - Nuclear proteins binding to a novel target sequence within the recombination
      hotspot regions of Bcl-2 and the immunoglobulin DH gene family.
AB  - The chromosomal breakpoints of follicular lymphomas carrying the
      t(14;18)(q32;q21) are known to be clustered within a 150-bp region in the major
      breakpoint region (mbr) of the Bcl-2 oncogene. We have demonstrated that nuclear
      proteins specifically bind to a novel target sequence within this 150-bp region
      and a region of Dxp genes, members of the immunoglobulin (Ig) diversity (DH) gene
      family. One protein, designated BCLF-1, appears to be specifically expressed in
      lymphoid lineage cells. Two other proteins, BCLF-2 and -3, bind only to the
      complementary single strand of the target sequence. The manner in which these
      proteins interact with the target sequence is similar to the interaction of the
      ReHF-1 and -2 proteins to the signal-like sequence at the chromosomal breakpoint
      junctions in patients with the t(8;14)(q24;q11) and t(1;14)(p32;q11)
      translocations. It was further suggested that the BCLF-1 is quite similar to or
      identical to the ReHF-1. It is therefore hypothesized that these conserved target
      sequences found in recombination hotspot regions may define novel sequence motifs
      recognized by two classes of DNA binding proteins. One class of DNA binding
      proteins is specifically expressed in lymphoid cells while the other class binds
      to the complementary single strand DNA. These binding activities may play a
      crucial role in chromosomal translocation in lymphoid neoplasms.

PMID- 8134114
TI  - Growth factor starvation of bcl-2 overexpressing murine bone marrow cells induced
      refractoriness to IL-3 stimulation of proliferation.
AB  - Murine bone-marrow derived BAF3 cells, over-expressing the human Bcl-2 gene
      product, showed considerably delayed onset of apoptosis when deprived of IL-3.
      Such Bcl-2-BAF3 cells arrested rapidly in the G1 phase of the cell cycle upon IL
      3 removal, then became refractory to IL-3 re-stimulation. The delay in IL-3
      induced proliferation of Bcl-2 over-expressing cells was due to down-regulation
      of a specific signalling pathway. In the refractory cells, IL-3 was able to
      stimulate protein tyrosine phosphorylation and c-myc mRNA accumulation, but not
      rapid Erk2 activation or cdc2 mRNA accumulation.

PMID- 8134115
TI  - Identification and cDNA cloning of single-stranded DNA binding proteins that
      interact with the region upstream of the human c-myc gene.
AB  - We have previously reported that a c-myc protein complex binds to the region
      upstream of the c-myc gene, where exist an origin of cellular DNA replication
      (ori) and a transcriptional enhancer. Both functions require a 21 bp long
      sequence, while the c-myc protein complex recognizes a 7 bp consensus therein. It
      was recently reported that single-stranded DNA binding proteins bound
      specifically to sequences that play roles in DNA replication or transcription. We
      examined for proteins binding to the single-stranded DNAs of the 21 bp element
      (myc(H-P)21). In a band shift assay with HL60 cells nuclear extract, probes of
      either the plus strand or the minus strand gave rise to specific signals.
      Mutation introduced within a short consensus (A/TCTA/TA/TT) present in both
      strands completely abolished binding in either case. Southwestern blotting
      analysis showed that proteins of molecular weight 105, 80, 50, 45, 40, 39.5 and
      14 kDa bound sequence-specifically to either strand and 22 kDa to minus strand to
      the cognate A/TCTA/TA/TT consensus. These single-stranded DNA binding proteins
      were named MSSP, c-myc gene single strand binding proteins. We attempted to
      isolate the cDNAs encoding these proteins by screening a human cDNA library with
      the plus single-stranded oligonucleotide as a probe. Among several positive
      clones, we have characterized one, termed MSSP-1. MSSP-1 produced in E. coli as a
      fusion protein with GST specifically interacted with single-stranded TCTTAT (plus
      myc(H-P)21) and ACT-ATT (in minus myc(H-P)21), the consensus of which can be
      referred to as A/TCTA/TA/TT. Sequence analysis of MSSP-1 cDNA revealed that two
      domains thereof are homologous to the RNA binding motifs common to several
      ribonucleoproteins. Interestingly, the MSSP-1/GST fusion protein specifically
      recognized myc(H-P)21 not only in single-stranded but also in double-stranded
      forms. Binding properties of MSSP-1 imply its functions in DNA replication.
      Furthermore, when the AT stretch in the SV40 ori core was substituted by TCTTAT,
      MSSP-1 promoted viral DNA replication depending on the consensus sequences.

PMID- 8134116
TI  - Cathepsin D maturation and its stimulatory effect on metastasis are prevented by
      addition of KDEL retention signal.
AB  - Cathepsin D is overexpressed in most primary breast cancers where its
      concentration is correlated with increased metastatic potential. To investigate
      the possible role and mechanism of this lysosomal protease in metastasis, we
      transfected low-metastatic rat tumor cells with wild-type human cathepsin D, or
      mutated forms obtained by insertion of a KDEL peptide signal responsible for ER
      retention, or a control KDAS peptide. The overexpressed pro-cathepsin D in wild
      type and KDAS clones was normally sorted and maturated in lysosomes. In KDEL
      clones, pro-cathepsin D was mostly retained in the ER or partially secreted by
      high-producer clones but was not maturated. While overexpressed cathepsin D
      increased experimental metastasis in athymic mice, the pro-cathepsin/D-KDEL was
      totally ineffective. Moreover, the effect of cathepsin D on metastasis did not
      seem to be due to saturation of the mannose-6-phosphate receptor since the
      secretion of two other rat lysosomal enzymes was unaffected by cathepsin D
      overexpression. We conclude that pro-cathepsin D overexpression facilitates tumor
      metastasis only when maturated into an active enzyme.

PMID- 8134117
TI  - Molecular cloning of a novel non-receptor tyrosine kinase, HYL (hematopoietic
      consensus tyrosine-lacking kinase).
AB  - We identified a novel non-receptor tyrosine kinase from a human megakaryoblastic
      cell line, UT-7, by means of a PCR-based cloning method. The HYL gene contained a
      SH2 and SH3 domain and a tyrosine kinase catalytic domain. The deduced amino acid
      sequence of the protein encoded by this gene was most homologous to CSK (c-src
      kinase). This gene and CSK shared some unique structural properties such as the
      absence of a myristylation signal and phosphorylation sites of tyrosine residues
      corresponding to tyrosines 416 and 527 of chicken p60c-src. Unlike CSK, the SH3
      domain of HYL was unique since the ALYDY motif was absent. Northern blot analysis
      revealed a 2.2 kb transcript in various myeloid cell lines but not in adult
      tissues except for the brain and the lung, whereas CSK mRNA was ubiquitously
      expressed. The expression of HYL was upregulated when these myeloid cells were
      differentiated by induction with phorbol myristate acetate. We named this gene,
      hematopoietic consensus tyrosine-lacking kinase, HYL. The HYL gene was assigned
      to chromosome 19 at band p13. It is suggested that HYL plays a significant role
      in the signal transduction of hematopoietic cells.

PMID- 8134118
TI  - Microsatellite instability in endometrial carcinoma.
AB  - Microsatellite instability (MI), detected as electrophoretic shifts in allele
      sizes of microsatellite DNA sequences, has been identified in some colorectal
      carcinomas. Investigators have previously attributed such microsatellite
      instability to replication errors (RER). The colorectal carcinomas with RER have
      been found to arise either sporadically or in association with the hereditary non
      polyposis colorectal cancer (HNPCC) syndrome. Because endometrial carcinoma is
      also commonly associated with HNPCC, we studied 30 cases of endometrial carcinoma
      to characterize the presence of MI in these neoplasms. Seven cases (23%) showed
      MI. Four cases showed both Type I (large shifts) and Type II (small shifts)
      mutation patterns and the remaining three cases showed Type I mutations only. We
      conclude that MI frequently occurs in endometrial cancers and that this type of
      genetic alteration may be an important pathogenetic feature of this tumor type.

PMID- 8134119
TI  - A transforming fragment within the direct repeat region of human herpesvirus type
      6 that transactivates HIV-1.
AB  - HHV-6 infection has been associated with several malignancies including non
      Hodgkin's lymphoma and Hodgkin's disease by the presence of high antibody titer
      and/or the presence of HHV-6 DNA. To understand their oncogenic potential, SalI
      restriction fragments from HHV-6 strain U1102 were transfected into NIH3T3 cells
      to assess transforming ability. A 3.9-kbp SalI-L DNA fragment spanning the
      junction of the direct repeat left (DRL) and unique long segment (UL) regions of
      HHV-6 induced foci of morphologically altered cells. The SalI-L transformed
      NIH3T3 focal lines induced tumors in nude mice within 2 weeks. The retention of
      HHV-6 specific DNA observed in SalI-L transformed cells and their tumor-derived
      lines suggest a possible maintenance function. Since both HHV-6 infection as well
      as transforming fragments from other DNA viruses have been shown to transactivate
      the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR), SalI
      L was examined for transactivation activity. SalI-L up-regulated HIV-1 LTR CAT 10
      15 fold in both monkey CV-1 and human T Jurkat cells. The further study of the
      SalI-L transforming fragment exhibiting transactivation of HIV-1 LTR will
      elucidate whether these two activities are encoded by a single gene and will aid
      in the understanding of the interaction between HHV-6 and HIV-1 as it relates to
      progression of AIDS and/or AIDS-related malignancies.

PMID- 8134120
TI  - Detailed analysis of the basic domain of the E2F1 transcription factor indicates
      that it is unique among bHLH proteins.
AB  - The E2F1 transcription factor binds to sites within the promoters of a number of
      cell cycle regulated genes through a basic-helix-loop-helix motif (bHLH). It is
      shown here that the basic region of E2F1 is distinct from that of all other bHLH
      proteins. The center of the basic region contains a helix breaking proline
      glycine pair, (P122, G123), implying a turn within this region. This is in
      contrast to the known bHLH containing proteins where the basic region is alpha
      helical. Substitution of P122 and G123 with alanines results in a significant
      reduction in DNA binding levels, with the predicted formation of an alpha-helix.
      Also in contrast to other bHLH proteins, mutations generated in conserved basic
      residues of E2F1 do not effect DNA binding. In addition, a single leucine (191)
      between helix no. 2 and the leucine zipper is required for DNA binding while the
      leucine zipper itself is not necessary. Finally, E2F1 interacts with all of the G
      residues in the sequence GGCGGGAAA while the A-residues are not required for DNA
      binding. The uniqueness of the E2F1 DNA binding domain is likely to play a role
      in its binding a DNA site that is distinct from that of all other bHLH proteins
      (CACGTG).

PMID- 8134121
TI  - Induction of apoptosis by adenovirus type 5 E1A in rat cells requires a
      proliferation block.
AB  - Infection with Ad5dl520EIB-, an adenovirus producing only the 243 residue E1A
      protein and lacking the E1B region, caused apoptosis in normal rat kidney (NRK)
      cells as judged by the production of nucleosomal DNA fragments. Apoptosis
      occurred only when the cells were growth-inhibited by cell-cell contacts in
      confluent cultures or by serum starvation and not when they were actively
      growing. In uninfected cultures, apoptosis also occurred at confluency, but more
      slowly than after infection. Studies with E1A deletion mutants of dl520E1B-
      showed that the regions of the E1A protein essential for induction of apoptosis
      were those in exon 1 required for binding to the cellular proteins p300 and pRb.
      Mutants defective at inducing apoptosis were previously found to be defective at
      inducing baby rat kidney cells to synthesize cellular DNA. In our experiments,
      cells underwent apoptosis when stimulated by E1A to proliferate under conditions
      where proliferation was blocked. It is possible that it was the proliferation
      block opposing the induction of proliferation that led directly to apoptosis.
      Circumstances leading to induction of apoptosis by c-myc (Evan et al., 1992) are
      similar and can be interpreted in a similar way.

PMID- 8134122
TI  - Down-regulation of MHC class I antigen in insulinoma cells controlled by the R1
      element of the H-2 enhancer.
AB  - Tumorigenesis in mice of the rat insulin promoter [RIP]-simian virus 40 tumor
      antigen [SV40 Tag] transgenic lineages, RIP1-Tag2 and RIP1-Tag4, is a process
      initiated by expression of SV40 Tag in pancreatic beta cells, evolution of islet
      cell hyperplasia and insulinoma appearance. Analysis of major histocompatibility
      complex [MHC] class I gene expression during this process revealed a normal level
      of MHC class I molecules at the surface of pancreatic islet cells of RIP1-Tag4
      mice, while hyperplastic islets from the same mice contained cells expressing a
      normal level and cells expressing a low level of MHC class I antigen. Insulinomas
      themselves expressed very low levels or no MHC class I gene product. Thus, down
      regulation of MHC class I gene appears to accompany tumor progression of SV40 Tag
      transformed beta islet cells. MHC class I antigen expression in a series of
      clonally derived cell lines of beta cell origin from different SV40 Tag-induced
      insulinomas ranged from quite low to undetectable, although expression was
      inducible by interferon-gamma. Nuclear run-on and transient transfection analyses
      indicated that expression of the MHC class I gene in these cells in controlled at
      the transcriptional level, and that the decreased expression is paralleled by
      reduced binding of transcription factors to the R1 element of the H-2 enhancer.

PMID- 8134123
TI  - SAS, a gene amplified in human sarcomas, encodes a new member of the
      transmembrane 4 superfamily of proteins.
AB  - Amplification of 12q13-14 occurs in a subset of human sarcomas including
      malignant fibrous histiocytoma and liposarcoma. This chromosomal region has
      previously been found to include a number of growth-related genes including the
      GLI proto-oncogene and the p53-associated protein, MDM2. We now report the
      characterization of SAS (sarcoma amplified sequence), a novel transcript found in
      this region. Sequence analysis demonstrates that SAS is a novel member of a
      transmembrane protein family (transmembrane 4 superfamily or TM4SF) thought to be
      involved in growth-related cellular processes. This observation adds a TM4SF
      protein to the cluster of genes at 12q13-14 frequently amplified in human
      sarcomas.

PMID- 8134124
TI  - Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse
      mammary epithelial cells.
AB  - At weaning the mammary gland undergoes a reductive remodelling process
      (involution) which is associated with the cessation of milk protein gene
      expression and programmed cell death of milk-producing epithelial cells. Elevated
      nuclear protein kinase A (PKA) activity was observed from one day post-lactation,
      paralleled by increased c-fos, junB, junD and to a lesser extent c-jun mRNA
      levels. AP-1 DNA binding activity was transiently induced and the AP-1 complex
      was shown to consist principally of cFos/JunD. Oct-1 DNA binding activity and Oct
      1 protein were gradually lost from the gland over the first 4 days of involution,
      whereas Oct-1 mRNA levels remained unchanged. Comparing nuclear extracts from
      normal mammary glands with nuclear extracts from glands which had been cleared of
      all epithelial cells 3 weeks after birth, revealed that PKA activation, AP-1
      induction and Oct-1 inactivation all are dependent on the presence of the
      epithelial compartment. The increased Fos/Jun expression and the inactivation of
      Oct-1 may be consequences of the increased PKA activity. A similar induction of
      AP-1 (cFos/JunD) was also observed in the involuting rat ventral prostate
      pointing to a possible role for AP-1 in programmed cell death.

PMID- 8134125
TI  - Modulation of transcriptional regulatory properties of p53 by HPV E6.
AB  - The E6 protein encoded by human papillomavirus type 16 (HPV16), a genital virus
      with oncogenic potential, can target cellular p53 for rapid degradation following
      the formation of a complex including the two proteins. Some studies suggest that
      the E6 proteins encoded by HPV6 and 11, viral types which are normally limited to
      benign lesions, may also interact with p53, although the association is weaker
      than that seen with HPV16 E6. The present study demonstrates that E6 proteins
      from HPV16 and HPV6 can modulate the transcriptional regulatory functions of p53
      in several cell types. A series of E6 mutants was used to show that association
      between E6 and p53 is necessary for this activity and that E6 proteins which
      retain the ability to associate with p53 but show no detectable degradation
      activity in vitro can, to some extent, abrogate p53 mediated transcriptional
      trans-regulation. This activity is augmented, however, by the ability of the E6
      protein to target bound p53 for rapid degradation. These results suggest that
      some degree of modulation of p53 function is necessary in the normal viral life
      cycle but also demonstrate a correlation between the efficiency of this activity
      and oncogenic potential of the virus.

PMID- 8134126
TI  - Predominantly tumor-limited expression of a mutant allele in a Japanese family
      carrying a germline p53 mutation.
AB  - Germline mutations of p53 have been implicated as a cause of cancer
      susceptibility in the Li-Fraumeni syndrome. Since inactivation of p53 has been
      suggested to play an important causative role in lung cancer, the present study
      of the prevalence of germline mutations in 148 patients with this neoplasm was
      performed. None of 138 randomly chosen patients were found to carry such
      mutations, while a single patient had a nonsense mutation at codon 213 among 10
      patients selected for early onset and/or occurrence of multiple primary cancers.
      In contrast to the previous report of biallelic expression of p53 in a case with
      a germline missense mutation, preferential expression of the wild-type allele was
      observed in the heterozygous state in both normal lung and peripheral blood
      lymphocytes of our case, whereas expression of mutant mRNA was readily detectable
      in her lung cancer in the absence of the remaining wild-type allele.
      Interestingly, the family history of the proband showed a mild aggregation of
      adulthood cancers and a high prevalence of stomach cancer, a rare component in
      American families affected by the syndrome. These observations suggest the
      presence of heterogeneity with regard to molecular and clinical features of
      germline p53 mutations.

PMID- 8134127
TI  - Two germ-line mutations affecting the same nucleotide at codon 257 of p53 gene, a
      rare site for mutations.
AB  - Codon 257 of the p53 gene is an extremely rare target for somatic mutations
      (accounting for only two of 1600 published mutations). We report here two
      constitutional mutations both affecting the second nucleotide of codon 257. A
      thymine to adenine transversion resulting in an amino acid change from leucine to
      glutamine was found in one proband who developed multiple independent malignant
      tumors (osteosarcoma, phyllodes tumor, soft-tissue sarcoma). Her mother died of
      early-onset breast cancer. In the other case, a deletion resulting in a
      frameshift in the C-terminal coding region of p53 was found in a woman who was
      diagnosed with breast cancer at age 34. This woman belongs to a family with
      features of Li-Fraumeni syndrome. In both cases, the p53 mutations identified in
      the proband was found in other members of the family. Codon 257, even if rarely
      mutated in somatic cells, may thus be an important target for germ-line
      mutations.

PMID- 8134128
TI  - Expression of mad, mxi1, max and c-myc during induced differentiation of
      hematopoietic cells: opposite regulation of mad and c-myc.
AB  - The Myc proto-oncoprotein family is considered to play an important role in the
      control of cell growth and differentiation. It appears that the interaction of
      Myc with its heterodimeric partner Max is essential for Myc function. Recently
      two other partners of Max, called Mad and Mxi1, have been identified. In an
      effort to gain insight into the network of these four proteins we have started to
      analyse the expression of the c-myc, max, mad and mxi1 genes at the mRNA level
      during hematopoietic cell growth and differentiation. In the human myeloid cell
      lines U-937, HL-60 and ML-1 c-myc expression was down-regulated as shown
      previously after induction of differentiation, whereas the expression of max was
      only slightly affected. In contrast to these two genes the expression of mad was
      induced upon differentiation in the three cell lines by TPA, retinoic acid,
      vitamin D3, dimethyl sulfoxide, and interferon-gamma and remained elevated for at
      least 3 days. A kinetic analysis showed that the induction of mad in U-937 in
      response to TPA was rapid (15 min) and at least in part transcriptional,
      reminiscent of immediate early genes. The expression of mxi1 was induced in U-937
      by some inducers but not in HL-60 or ML-1. Its induction occurred slowly, peaking
      around 48 h. These analysis thus suggest that the expression of mad and c-myc is
      inversely regulated during induced hematopoietic differentiation.

PMID- 8134130
TI  - Isolation of a gene encoding a novel receptor tyrosine kinase from differentiated
      embryonic stem cells.
AB  - A mouse gene encoding a receptor tyrosine kinase, designated Embryonic receptor
      kinase (EmRK2), was isolated from embryoid bodies (EBs) generated by
      differentiating embryonic stem (ES) cells in culture for 6 days. Sequence
      analysis of EmRK2 cDNA clones predicts a receptor with a 755 amino acid
      extracellular region with seven immunoglobulin-like domains, a transmembrane
      region, and a 552 amino acid cytoplasmic region containing the kinase domain. The
      kinase domain is interrupted by a stretch of hydrophilic amino acids, the kinase
      insert. EmRK2 is expressed in embryoid bodies, in whole embryos at day 10 and 12
      of gestation, and in the embryonic yolk sac and the fetal liver. On the basis of
      sequence homology, EmRK2 is likely to be the mouse homologue of human flt, a
      receptor for vascular endothelial growth factor, and as such, could encode an
      endothelial cell specific receptor tyrosine kinase.

PMID- 8134129
TI  - Identification of a gene encoding a novel protein-tyrosine kinase containing SH2
      domains and ankyrin-like repeats.
AB  - Using the polymerase chain reaction with primers corresponding to conserved
      regions in the kinase domain of protein-tyrosine kinases, we amplified segments
      of several protein-tyrosine kinase genes from Hydra vulgaris, a member of the
      ancient metazoan phylum Cnidaria. Characterization of cDNA clones for one of
      these genes, HTK16, revealed that it encodes a non-receptor protein-tyrosine
      kinase with two SH2 domains but no SH3 domain. In this regard the predicted HTK16
      protein resembles two mammalian non-receptor protein-tyrosine kinases, the
      products of the ZAP-70 and syk genes. However, the HTK16 protein contains five
      ankyrin-like repeats, a structural motif which has not previously been found in
      protein-tyrosine kinases. The HTK16 protein also contains a potential tyrosine
      phosphorylation site in its carboxyl-terminal tail which resembles the
      phosphorylation site in members of the src family. RNA hybridization analysis
      indicates that the HTK16 gene is expressed in epithelial cells, cells which also
      express the Hydra homologue of the src protein. Our finding of the HTK16 gene in
      Hydra indicates that diversification of genes encoding non-receptor protein
      tyrosine kinases was a very early event in metazoan evolution.

PMID- 8134131
TI  - Functional dissection of the transcription factor Elk-1.
AB  - The ternary complex factor Elk-1 belongs to the Ets oncoprotein family. We
      demonstrate that this transcription factor is localized predominantly in the
      nucleus, for which at least two regions of Elk-1 are required. One of these
      regions is part of the N-terminal ETS-domain, while the other encompasses amino
      acids 137-157. In conjunction with the ETS-domain, which mediates autonomous
      binding of Elk-1 to some DNA target sequences, the conserved B-region is both
      necessary and sufficient for ternary complex formation with the c-fos serum
      response element and the serum response factor. However, the B-region must be
      linked to the ETS-domain by a spacer. Furthermore, the B-region impedes
      autonomous DNA-binding, possibly by masking the ETS-domain. A point mutation
      within the ETS-domain, homologous to the ts1.1 point mutation of v-Ets in the E26
      virus, affects DNA-binding of Elk-1 in a temperature-dependent manner, which by
      analogy might be causative for the altered phenotype of ts1.1 E26. Finally we
      show that amino acids 83-428 contribute to Elk-1 mediated transactivation. In
      particular, the region 376-404 is indispensable for transactivation, while
      flanking amino acids on both sides are only required for enhancement of
      transcriptional efficacy.

PMID- 8134132
TI  - The Myb oncogene product induces DNA-bending.
AB  - The nuclear oncogene v-myb and its cellular counterpart c-myb code for proteins
      that bind to DNA in a sequence specific manner and act as regulators of
      transcription. The Myb protein contains DNA binding and trans-regulatory domains
      which are important for its function. The DNA binding domain of Myb protein has
      been shown to contain three imperfectly conserved repeats of 50-52 amino acids
      that constitute the amino terminal end. In this communication, we show that Myb
      protein induces conformational change in DNA after protein-DNA complex formation.
      Circular permutation assays indicate that Myb protein induces DNA bending at the
      site of binding. Phasing analysis confirm the DNA bending and allowed the
      detection of relative orientation of bend. Myb proteins which comprise only DNA
      binding domains either with three repeats or two repeats also bend DNA in the
      same orientation as the larger proteins with both DNA-binding and transactivating
      domains. However, the transactivating region seems to influence the magnitude of
      bend angle. We used molecular modeling to analyse the structure of Myb-DNA
      complex formation resulting in the bending of DNA. Data presented here show that
      Myb protein, like other transcriptional regulators, bends DNA upon binding
      allowing the interaction of regulatory elements.

PMID- 8134133
TI  - Frequent homozygous deletions of the D13S25 locus in chromosome region 13q14
      defines the location of a gene critical in leukaemogenesis in chronic B-cell
      lymphocytic leukaemia.
AB  - Cytogenetic studies of B-cell chronic lymphocytic leukaemia show structural
      abnormalities involving the 13q14 chromosome region as the only karyotypic change
      in a significant proportion of tumours. This observation suggests the location of
      a gene important in leukaemogenesis. A series of 68 BCLL tumours have been
      analysed for allele loss using a series of probes from 13q14. Using intragenic
      polymorphic markers from the retinoblastoma predisposition gene LOH was observed
      in 25% of tumours including 3/6 showing cytogenetically obvious deletions of the
      13q14 region and 3/6 showing translocations involving 13q14. However, three
      deletions with proximal breakpoints in 13q14 did not show allele loss,
      demonstrating that the breakpoint lay distal to RB1. Using the D13S25 locus,
      which lies 1.6 cM distal to RB1, allele loss was seen in 90% of tumours with
      structural rearrangements of 13q14 and 75% of tumours with an apparently normal
      karyotype. 50% of these tumours showed homozygous loss of D13S25, suggesting that
      a 'tumour suppressor gene' lies in this region. The more distal D13S31 locus, 1
      cM distal to D13S25, was infrequently involved in allele loss demonstrating that
      the minimum region of overlap for homozygous deletions is approximately 1 Mbp
      around the D13S25 locus.

PMID- 8134134
TI  - Inducible regulatory elements in the human cyclin D1 promoter.
AB  - To be able to elucidate the function of cyclin D1 in the control of cell cycle
      progression and its role as an oncogene in tumorigenesis, it is of paramount
      importance to understand the mechanisms involved in the regulation of its
      expression. In the present study, we have cloned the human cyclin D1 gene and
      analysed the structure and function of 3kb of its 5'-flanking region. Several
      regulatory regions involved in both basal level and serum-induced expression were
      identified, two of which turned out to be of particular interest. One of these
      regions is involved in serum induction and is located 848-944 bp upstream of the
      initiation site. In agreement with this result, in vivo footprinting revealed a
      novel, strongly inducible protein binding site around positions -928 to -921. A
      second constitutively occupied binding site was mapped to a potential CRE at
      position -52. Cotransfection experiments showed that the cyclin D1 promoter is
      inducible by c-Jun, and that this induction is mediated predominantly through the
      protected putative CRE at -52.

PMID- 8134135
TI  - George Shambaugh, Jr.: 90 and on the way to 100--what a role model!

PMID- 8134136
TI  - Autorotation test abnormalities of the horizontal and vertical vestibulo-ocular
      reflexes in panic disorder.
AB  - Patients with panic disorder often describe dizziness as a disturbing symptom,
      with more severe episodes reported than in other psychiatric populations.
      Nineteen patients diagnosed as having a panic disorder were tested for vestibulo
      ocular (VOR) abnormalities with the Vestibular Autorotation Test (VAT), a
      computerized test of the high-frequency (2 to 6 Hz) VOR. The patients were
      unselected for the presence or absence of balance disorders. Results showed VOR
      abnormalities, relative to a normal population, in the horizontal and/or vertical
      VORs of all 19 patients. Vestibulo-ocular reflex asymmetries were commonly
      present. Because the VAT tested the VOR over a frequency range encountered during
      common daily activities, the observed abnormalities could result in a
      perceptually moving visual field (oscillopsia). We hypothesize that the resulting
      experience of a visual-vestibular disturbance--perhaps in a biologically or
      psychologically predisposed individual--is catastrophically misinterpreted,
      leading to more bodily symptoms and anxiety. These could then contribute to more
      misinterpretation in a positive feedback sense, ultimately leading to a panic
      attack.

PMID- 8134137
TI  - Efficacy of surgical treatments for squamous cell carcinoma of the temporal bone:
      a literature review.
AB  - A review of all publications dealing with surgical treatment for squamous cell
      carcinomas of the temporal bone was performed. No randomized or nonrandomized
      control studies were identified. All studies were case series without control
      subjects. Twenty-six of 96 publications, which contained information on 144
      patients, were analyzed. Several inferences are suggested by the available
      evidence; however, these areas should be investigated by properly designed
      randomized clinical trials: (1) patients with carcinoma that is confined to the
      external auditory canal have similar survival, regardless of whether
      mastoidectomy, lateral temporal bone resection (TBR), or subtotal TBR is
      performed: the addition of radiation therapy to lateral TBR does not appear to
      improve survival; (2) when disease extends into the middle ear, survival of
      patients treated with subtotal TBR appeared to be improved over those treated
      with lateral TBR or mastoidectomy: it remains uncertain if the addition of
      radiation therapy to mastoidectomy improves survival; (3) the value of surgical
      resection when carcinoma extends to involve the petrous apex remains unclear; (4)
      resection of involved dura mater does not appear to improve survival; however,
      incomplete data regarding margins of resection were reported; and (5)
      determination of the value of resection of involved brain parenchyma or internal
      carotid artery will require further study.

PMID- 8134138
TI  - Sensory interaction posturography in patients with peripheral vestibular
      disorders.
AB  - The results of posturography, using all sensory inputs, are compared with
      recordings when one or more of the sensory inputs are altered by the test
      conditions. This gives an idea of the sensory interaction in central compensation
      in the vestibulospinal reflex. Positive and negative effects could be observed in
      patients with peripheral vestibular disorders.

PMID- 8134139
TI  - Primary surgical management for rehabilitation of the paralyzed eye.
AB  - Protection of the eye is the primary concern in managing the patient with facial
      paralysis; however, the aesthetic consequences cannot be overlooked.
      Lagophthalmos has traditionally been treated with frequent ocular lubrication,
      medical eye care, and tarsorrhaphy. This approach is fraught with the
      difficulties of poor patient compliance and unacceptable cosmesis. We suggest a
      protocol for the complete ocular management with emphasis on immediate rather
      than delayed surgical rehabilitation as a primary therapy in facial paralysis.
      Gold weight implantation to the upper lid and tightening of the lower lid at the
      lateral canthus are simple and reliable procedures that provide immediate
      functional and aesthetic improvement. This surgical technique has extremely low
      morbidity and is reversible should facial function return. We have used this
      protocol in more than 30 patients with excellent results.

PMID- 8134140
TI  - Dizziness in aging: a retrospective study of 1194 cases.
AB  - In the Royal Victoria Hospital dizziness clinic, 1194 of 9767 (12.22%) patients
      were 70 years of age or older on the day of the first visit. There were 750 women
      and 444 men, with no difference in age distribution (p > 0.9). In 367 (27.04%)
      cases (percentages given as "cases" refer to the number of diagnoses [N = 1357],
      not the number of patients [N = 1194]), the symptoms were nonspecific, and the
      diagnosis was uncertain. In 530 (39.13%) patients, paroxysmal positional vertigo
      was either confirmed or strongly suspected. In the 241 of 254 (94.88%) confirmed
      cases, the observed paroxysmal nystagmus was compatible with excitation of the
      posterior semicircular canal. In 119 (8.77%) patients, the dizziness could not be
      attributed to neurologic or vestibular disease. Meniere's disease, vestibular
      neuronitis, vascular episodes, and tumors were next in prevalence. The following
      conclusions were reached: (1) although no difference was found in age
      distribution between women and men, dizziness was more prevalent among women,
      which may be because of the higher survival rate of women; (2) the prevalence of
      paroxysmal positional vertigo was high, with apparent involvement of the
      posterior semicircular canal in most cases (it is strongly suspected that
      paroxysmal positional vertigo is frequently misdiagnosed as vascular disease in
      advanced age); and (3) multisensory deficits, drugs, or systemic diseases, common
      in the elderly, may cause dizziness. Syndromes affecting the vestibular function,
      however, may be more prevalent in advanced age than is generally estimated.

PMID- 8134141
TI  - Total and partial ossicular replacement prostheses in children.
AB  - Although ossicular reconstruction in children may carry a risk of failure because
      of recurrent middle ear disease, the procedure offers the potential for restoring
      binaural hearing during the school years when it is so critical. Of a series of
      45 reconstructions with total and partial ossicular replacement prostheses, 6
      were extruded for a surgical success rate of 87%. Of the successful cases, 74%
      had air-bone gaps of 30 dB or better, and 74% had speech reception thresholds of
      30 dB or better on initial postoperative audiogram. Outcomes for these children
      were comparable with those reported for adults, supporting the value of early
      reconstruction.

PMID- 8134142
TI  - Covariation of tinnitus pitch and the associated emission: a case study.
AB  - Tinnitus in one female subject was found to be related to numerous (as many as
      21) bilateral spontaneous otoacoustic emissions. The association of tinnitus and
      spontaneous otoacoustic emissions was empirically supported by the
      masking/suppression demonstration. The subject reported that her tinnitus
      occurred primarily in her right ear, which had linked, quasi-stable spontaneous
      otoacoustic emissions not found contralaterally. During one menstrual cycle, a
      pure tone was adjusted to match the predominant tinnitus pitch. The frequency of
      the tone generally followed the day-to-day shifts in the frequency of the
      associated spontaneous otoacoustic emission. The frequencies of these tones were
      a local minimum near the onset of menstruation, reaching a local maximum after
      menstruation.

PMID- 8134143
TI  - Spontaneous cervical emphysema in a child.

PMID- 8134144
TI  - Reconsideration on the hyoid syndrome.

PMID- 8134145
TI  - Stridor in an adolescent: an unusual symptom.

PMID- 8134146
TI  - Inner ear cholesteatoma: an embryologic aberration.

PMID- 8134147
TI  - Bay leaf: an uncommon foreign body of the hypopharynx.

PMID- 8134148
TI  - Desmoplastic fibroma of the parapharyngeal space.

PMID- 8134149
TI  - A prospective pilot study comparing single lag screw osteosynthesis vs.
      maxillomandibular fixation.

PMID- 8134150
TI  - Perichondrial elevator for thyroplasty type I surgery.

PMID- 8134151
TI  - The "puppet maneuver" for stapes surgery.

PMID- 8134153
TI  - Resource guide for Pennsylvania physicians 1994. Pennsylvania Medical Society
      Directory.

PMID- 8134152
TI  - Malignant melanoma of the head and neck.

PMID- 8134154
TI  - Contrasting clinical and statistical significance within the research setting.
AB  - When designing a clinical trial or study, the value of the following interrelated
      parameters should be determined prior to collecting data: clinical significance,
      statistical significance, power, and sample size. Too often, clinical importance
      and the other design issues are ignored and only statistical significance
      dictates the conclusions of the study. In order to evaluate the frequency that
      each of these design parameters is addressed in the published literature, the
      topic of pulmonary function tests (specifically forced vital capacity) was
      chosen, and all relevant articles for one year (1990) were identified using
      Minnesota MEDLINE. A total of 121 articles met the selection criteria and were
      reviewed. Of all the articles, 13.2% discussed clinical significance, 21.5%
      discussed sample size, and only 5.0% addressed statistical power. As expected,
      the majority of the articles (92.6%) discussed statistical significance (P
      values). None of the articles mentioned all four factors. When choosing the level
      of clinical significance several methods may be used. Such might be well
      established in certain clinical areas or available from previous publications and
      references or they may be attainable from pilot study data and, in the absence of
      any prior information, a clinician may use personal experience. To minimize
      subjectivity, the clinical effect-size can be based on the population
      distribution of the measurement of interest.

PMID- 8134155
TI  - Bone turnover in asthmatic children treated with oral prednisolone or inhaled
      budesonide.
AB  - Biochemical markers of bone turnover were studied in prepubertal school children
      with asthma in two randomized double-blind crossover trials with run-in,
      treatment, and wash-out periods of 2 weeks. One group (n = 11) was treated with
      2.5 and 5.0 mg prednisolone, the other (n = 14) with 200 and 800 micrograms
      inhaled budesonide per day. Serum osteocalcin, serum total alkaline phosphatase,
      fasting urinary excretion of hydroxyproline and calcium, serum 25-hydroxyvitamin
      D, and 1,25 dihydroxyvitamin D were assessed. A dose-related reduction of serum
      osteocalcin (Page's test for trend: P = 0.04; z = -2.3) and of the fasting
      urinary hydroxyproline:creatinine ratio (Page's test for trend: P = 0.05; z = 
      2.0) was found in the children who were treated with prednisolone. Inhaled
      budesonide was not associated with statistically significant effects on any of
      the biochemical markers. Short-term treatment with low daily doses of
      prednisolone may cause a suppression of bone turnover in children with asthma. To
      reduce the risk of adverse effects on bone turnover, doses of inhaled budesonide
      up to 800 micrograms daily may be preferable to low doses of prednisolone. Bone
      turnover remains to be evaluated during long-term treatment.

PMID- 8134156
TI  - Evolution of pulmonary function during an acute exacerbation in hospitalized
      patients with cystic fibrosis.
AB  - Few objective criteria have been validated for serial clinical monitoring in
      patients with cystic fibrosis (CF) during pulmonary exacerbations. While
      pulmonary function tests (PFT) are often used to monitor clinical improvement, it
      is not known which test correlates most closely with clinical improvement. To
      answer this, we measured routine PFT in 58 patients with CF before, during, and
      at discharge after 2-3 week hospital admission in 71 episodes of pulmonary
      exacerbation. Patients with CF were discharged based on clinical, radiological,
      and laboratory criteria. In general, all PFTs improved at midadmission and
      improved further by discharge, at which time forced expiratory volume in 1 second
      (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity
      (FEF25-75), vital capacity (VC), maximal voluntary ventilation (MVV), and oxygen
      saturation by pulse oximetry (SPO2) increased. The residual volume to total
      capacity ratio (RV/TLC) and the slope of phase 3 in the single breath N2 washout
      curve (SP3 N2) decreased. The change in SP3 N2 was significantly greater than in
      any other PFT (P < 0.01 vs. VC and FEV1; P < 0.02 vs. RV and P < 0.001 vs. SPO2).
      A calculated optimal cut-off value for SP3 N2 improvement was significantly more
      sensitive in identifying patient improvement at discharge than any other
      pulmonary function test (P = 0.005). We speculate that clinical improvement in
      patients with CF is closely linked to improved distribution of ventilation.

PMID- 8134157
TI  - Cardiorespiratory effects of conventional and high frequency ventilation in
      rabbits with bilateral pneumothoraces and surfactant depleted lungs.
AB  - We compared high frequency ventilation (HFV) to conventional mechanical
      ventilation (CMV) under normoxic and normocapnic condition in surfactant depleted
      rabbits with bilateral pneumothoraces. We hypothesized that lower airway
      pressures would be required with HFV under these conditions. We applied CMV and
      HFV in 8 anaesthetized rabbits with a prototype ventilator at frequencies of 30,
      100, 200, and 300 cycles/min. A positive end-expiratory pressure (PEEP) just
      below the pressure sufficient to open the air leak from the pneumothoraces was
      applied at all frequencies. Airway pressures, gas exchange, heart rate, and mean
      arterial pressure were recorded. Peak airway pressure decreased significantly
      from 2.50 to 2.10 kPa when the frequency of ventilation was increased from 30 to
      300 cycles/min. There were no significant changes in mean airway pressure, PaO2,
      arterial pH, heart rate, and mean arterial pressure when HFV was compared to CMV.
      In conclusion, during HFV peak airway pressures measured at the mouth were
      decreased. Our ability to maintain adequate gas exchange in the face of ongoing
      pulmonary air leaks may reflect lower alveolar pressures.

PMID- 8134158
TI  - Neonatal meconium aspiration syndrome and respiratory morbidity during infancy.
AB  - Respiratory morbidity in the first 6 months of life of 35 infants who had had
      neonatal meconium aspiration syndrome (MAS) was compared to that of 70 controls,
      also born at term, matched for gender and ethnic origin. The number of infants in
      the two groups who were symptomatic was compared. Infants were described as
      symptomatic if, following discharge from hospital, they had at least one episode
      of wheezing and/or coughing which lasted for 3 days or more. There was no
      significant difference between the two groups regarding parental smoking or the
      proportion of infants who had a family history of atopy. A significantly greater
      proportion of the MAS group (49%) than of the control group (20%) was symptomatic
      at follow-up. Eight (23%) infants with MAS and 2 (3%) controls had symptoms which
      necessitated regular bronchodilator therapy. The 8 infants with MAS who were on
      maintenance bronchodilator therapy had required significantly longer neonatal
      respiratory support and had larger lung volumes at follow-up than the other 27
      infants. We conclude that neonatal meconium aspiration syndrome is associated
      with increased respiratory morbidity in the first 6 months of life.

PMID- 8134160
TI  - Bronchial mucous gland adenoma presenting as bronchogenic cyst.

PMID- 8134159
TI  - Severe hypoxemia in children with upper airway obstruction during sleep does not
      lead to significant changes in heart rate.
AB  - Life-threatening cardiac arrhythmias, including bradyarrhythmias, are well-known
      sequelae of obstructive sleep apnea syndrome (OSAS) in adults and are associated
      with apnea and severe hypoxemia. Since the clinical expression of OSAS in
      children is different, we questioned whether arrhythmias are a common feature of
      pediatric OSAS. Therefore, we analyzed R-R interval patterns from 12 subjects
      (age 8 months to 14 years) with OSAS in detail. The diagnosis of pediatric OSAS
      is based on clinical signs of loud snoring and paradoxical respiratory efforts,
      as well as elevated end-tidal carbon dioxide tension (PETCO2) and major phasic
      decreases of oxyhemoglobin saturation (SaO2). Two hundred and nine episodes of
      severe hypoxemia, defined as SaO2 values < or = 85% lasting > or = 30 seconds,
      were identified. Only 29 (14%) of these episodes were associated with obstructive
      apneas. The R-R intervals were analyzed before and during each desaturation.
      Compared to baseline, mean and minimum R-R intervals (RRmean, RRmin) decreased
      during the desaturation episodes (P < 0.05), while maximum R-R interval (RRmax)
      increased (P < 0.05). Although the absolute changes in all parameters were
      significantly different from baseline, the magnitude of these changes was small,
      with a mean of -5.3%, -12.2%, and 10.4% for RRmean, RRmin, and RRmax,
      respectively. No child had life-threatening arrhythmias. Although severe
      hypoxemia existed in these children, the magnitude of the R-R interval changes
      was modest, and profound bradycardia as described in adults, was rare.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8134161
TI  - "Bronchitis" obliterans and prolonged transient hypogammaglobulinemia in a child.

PMID- 8134162
TI  - Deficient priming activity of newborn cord blood-derived polymorphonuclear
      neutrophilic granulocytes with lipopolysaccharide and tumor necrosis factor-alpha
      triggered with formyl-methionyl-leucyl-phenylalanine.
AB  - Newborn infants are more susceptible to bacterial infections than adults. This
      susceptibility has been attributed to defects in humoral and cellular activity.
      Host cellular activity can be modified by factors produced by bacteria or the
      host in response to infection. We assessed the effect of two factors associated
      with gram-negative bacterial infection, lipopolysaccharide (LPS) and TNF-alpha,
      on polymorphonuclear neutrophilic granulocytes (PMN) obtained from adult or
      newborns (umbilical cord blood). PMN were primed in vitro with LPS (10
      micrograms/L) or TNF-alpha (10(-9) M) for 45 min and then assessed, using a
      chemiluminescence (CL) assay as an indicator of oxidative radical production with
      formyl-methionyl-leucyl-phenylalanine as the trigger for CL initiation. CL
      activity of unprimed PMN was similar for adults and newborns (13.3 and 13.7 CL
      units, respectively). After priming with LPS, CL activity was increased to 43.4
      CL units for PMN from adults but to only 17.6 CL units for PMN from newborns (p <
      0.001, adults versus newborn increment). Priming of PMN with LPS was most
      effective when autologous plasma was present. Using FITC-conjugated LPS and a
      flow cytometry assay, we could demonstrate no difference between the binding
      affinity of LPS for adult and newborn PMN. However, formyl-methionyl-leucyl
      phenylalanine binding studies indicated that adult PMN had a higher number of
      binding sites. TNF-alpha priming of newborn PMN was also ineffective. Adult PMN
      increased CL activity by 3.9-fold when primed with TNF-alpha, whereas newborn PMN
      increased by only 1.75-fold (p < 0.005). This priming deficiency was not
      attributable to TNF-alpha receptors because phycoerythrin-conjugated TNF-alpha
      was associated with PMN from adults and newborns equally. Thus, PMN from newborns
      are not primed effectively in vitro with LPS or TNF-alpha. This defect may
      contribute to neonatal susceptibility to bacterial infection.

PMID- 8134163
TI  - Elevated interleukin-1 expression in human neonatal neutrophils.
AB  - Newborn infants have an increased morbidity and mortality from infection caused
      in part by diminished polymorphonuclear leukocyte (PMN) function and impaired
      recruitment of PMN to sites of inflammation. Recent studies in our laboratory and
      others have demonstrated the in vitro expression of several cytokines, including
      IL-1-beta, in adult human peripheral blood PMN. Because newborn infants have an
      impaired inflammatory response, we sought to compare the synthetic capability and
      regulation of cytokine expression in neonatal and adult PMN. In our present
      studies, we found that tumor necrosis factor-alpha and lipopolysaccharide could
      induce IL-1-beta expression in both neonatal and adult PMN and that neonatal PMN
      produced significantly more IL-1-beta when compared with adult PMN. The PMN
      chemotactic peptide fMet-Leu-Phe did not induce IL-1-beta expression in either
      adult or neonatal PMN. Elevated cytokine expression by neonatal PMN may play an
      important role in the regulation of the immune and inflammatory systems at sites
      of injury and infection in neonates.

PMID- 8134164
TI  - Establishment and characterization of a novel human monocytic leukemia cell line
      (KP-1) expressing scavenger receptor.
AB  - A new monocytic leukemia cell line (KP-1) was established from a 2-y-old Japanese
      girl with acute monocytic leukemia. The KP-1 cells were maintained in suspension
      culture with a doubling time of 96 h. The cells were positively stained with
      alpha-naphtyl butyrate esterase, but not with naphthol AS-D chloroacetate
      esterase, myeloperoxidase, and periodic acid-Schiff reagent. Cell surface marker
      analysis revealed that the cells were CD4, CD11a, CD11c, CD13, CD14, CD18, CD33,
      and HLA-DR positive. Karyotype analysis revealed near diploidy (47 XX) and a
      translocation t(11;19) was found. When treated with 12-o-tetradecanoylphorbol 13
      acetate, KP-1 cells became tightly adherent, showed the enhanced reactivity for
      alpha-naphtyl butyrate esterase, and produced several monokines such as IL-1
      beta, tumor necrosis factor-alpha, and macrophage colony-stimulating factor.
      Immunoelectron microscopy demonstrated that the human macrophage scavenger
      receptor was expressed after 12-o-tetradecanoylphorbol-13-acetate treatment, and
      the cells accumulated a large amount of cholesterol esters in the presence of
      acetylated LDL. Compared with another human monocytic leukemia cell line, THP-1,
      KP-1 expressed scavenger receptor and accumulated cholesterol ester more rapidly
      in the presence of 12-o-tetradecanoyl phorbol-13-acetate and acetylated LDL.
      Scatchard analysis using 125I-labeled acetylated LDL revealed a typical
      saturation curve with an apparent kd of 1.7 x 10(-7) M and 3400 binding sites per
      cell. KP-1 retained the characteristics of monocyte-macrophage lineage cells and
      will facilitate the in vitro studies of the pathologic and physiologic roles of
      scavenger receptors.

PMID- 8134165
TI  - Interferon-gamma corrects the respiratory burst defect in vitro in monocyte
      derived macrophages from glycogen storage disease type 1b patients.
AB  - Glycogen storage disease (GSD) type 1b is accompanied by decreased respiratory
      burst activity in peripheral blood phagocytic cells (i.e. monocytes and
      neutrophils). To elucidate whether this depressed respiratory burst was due to an
      intrinsic defect of phagocytic cells or due in part to in vivo host factors, we
      examined superoxide anion (O2-) production in monocytes from five GSD 1b patients
      cultured 9 d in vitro to allow for differentiation into macrophages (MDM). O2-
      production in MDM was measured in response to concanavalin A, fMet-Leu-Phe, and
      phorbol myristate acetate (PMA) stimulation. GSD 1b MDM had significantly
      depressed O2- generation with fMet-Leu-Phe and concanavalin A stimulation;
      however, unlike peripheral blood monocytes, GSD 1b MDM responded to PMA
      stimulation with O2- production comparable to healthy control donors. The
      cytokine interferon-gamma (IFN-gamma) has been shown to enhance O2- production in
      MDM. When GSD 1b MDM were cultured in the presence of IFN-gamma (1 x 10(5) U/L),
      O2- production in response to fMet-Leu-Phe, concanavalin A, and PMA was enhanced
      to rates similar to those of control MDM cultured in the presence of IFN-gamma.
      Thus, the respiratory burst defect observed in circulating phagocytic cells is
      also present in vitro in cultured GSD 1b MDM. However, in contrast to circulating
      phagocytic cells, depressed O2- production in GSD 1b MDM is selective to receptor
      mediated activation, but not to PMA stimulation. This defect is correctable after
      short-term treatment with IFN-gamma, suggesting a role for IFN-gamma in treating
      the phagocytic defect in this disease.

PMID- 8134166
TI  - Stable-isotope dilution analysis of D- and L-2-hydroxyglutaric acid: application
      to the detection and prenatal diagnosis of D- and L-2-hydroxyglutaric acidemias.
AB  - A stable-isotope dilution assay has been developed for quantitation of D- and L-2
      hydroxyglutaric acids in physiologic fluids. D- and L-2-hydroxyglutaric acids are
      separated as the O-acetyl-di-(D)-2-butyl esters. The method uses D,L-[3,3,4,4
      2H4]-2-hydroxyglutaric acid as internal standard with ammonia chemical
      ionization, selected ion monitoring gas chromatography-mass spectrometry. For 13
      patients with L-2-hydroxyglutaric aciduria, the concentrations of L-2
      hydroxyglutaric acid were urine, 1283 +/- 676 mmol/mol creatinine (range, 332
      2742; n = 12 patients); plasma, 47 +/- 13 mumol/L (range, 27-62; n = 8);
      cerebrospinal fluid, 62 +/- 30 mumol/L (range, 34-100; n = 6). In a child with D
      2-hydroxyglutaric aciduria, the levels of D-2-hydroxyglutaric acid were urine,
      1565 +/- 847 mmol/mol creatinine (range, 729-2668; n = 4); plasma, 61 +/- 14
      mumol/L (range, 46-73; n = 3); cerebrospinal fluid, 15 and 25 mumol/L (n = 2).
      Control concentrations of D- and L-2-hydroxyglutaric acids were (D:L): urine (n =
      18), 6.0 +/- 3.6 mmol/mol creatinine (range, 2.8-17): 6.0 +/- 5.4 (range, 1.3
      19); plasma (n = 10), 0.7 +/- 0.2 mumol/L (range, 0.3-0.9): 0.6 +/- 0.2 (range,
      0.5-1.0); cerebrospinal fluid (n = 10), 0.1 +/- 0.1 mumol/L (range, 0.07-0.3):
      0.7 +/- 0.6 (range, 0.3-2.3). Investigation of control amniotic fluid (n = 10)
      revealed the following values (D:L): 1.2 +/- 0.4 mumol/L (range, 0.6-1.8): 4.0 +/
      0.7 (range, 3.1-5.2), suggesting the feasibility of prenatal diagnosis in
      families at risk.

PMID- 8134167
TI  - Valproic acid impairs carnitine uptake in cultured human skin fibroblasts. An in
      vitro model for the pathogenesis of valproic acid-associated carnitine
      deficiency.
AB  - The mechanisms of valproate-associated carnitine deficiency are controversial.
      The urinary excretion of valproylcarnitine is insufficient to account for tissue
      carnitine depletion. To explore this mechanism, we studied the effects of
      valproic acid (VPA) on carnitine uptake in cultured human skin fibroblasts by the
      method of Tein et al. (Pediatr Res 28:247-255, 1990). Fibroblasts were
      preincubated with varying concentrations (0-2000 microM) of VPA for 1, 3, 5, 7,
      10, 14, 21, and 28 d and then incubated with fixed carnitine concentrations of 50
      microM (normal physiologic concentration), 20 microM (as seen in secondary
      carnitine deficiency disorders), or 5 microM (as seen in the plasma membrane
      carnitine transport defect). There was an exponential dose-dependent decrease in
      carnitine uptake with increasing VPA concentrations, and the relative inhibitory
      effect was the same for all three carnitine concentrations. The mean percentages
      +/- SD (n-1) of residual carnitine uptake for all combined preincubation periods
      (1-28 d) and combined carnitine concentrations (5, 20, and 50 mumol/L) with
      increasing concentrations of VPA varied from 83.4 +/- 2.6% (10 microM VPA) to
      56.7 +/- 0.1% (500 microM) to 19.8 +/- 1.3% (2000 microM). The degree of
      inhibition was directly proportional to the time of VPA preincubation and
      parallel for all three carnitine concentrations; the longer the preincubation
      period, the lower the toxic dose of VPA (to a minimum of 450 microM), resulting
      in a 50% suppression of carnitine uptake (TD50).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134168
TI  - Placental 5-deiodinase activity and fetal thyroid hormone economy are unaffected
      by selenium deficiency in the rat.
AB  - In adult male rats, selenium deficiency results in a near complete loss in the
      selenoprotein 5'-deiodinase in the liver, resulting in decreased peripheral
      deiodination of thyroxine (T4) and increased serum T4 concentrations. Serum
      3,5,3'-triiodothyronine concentrations are normal or slightly decreased, and
      serum 3,3',5'-triiodothyronine concentrations are normal or slightly increased in
      selenium-deficient rats. We now report the effects of selenium deficiency on
      maternal and fetal thyroid hormone economy and on placental 5-deiodinase activity
      in the rat. Weanling female rats were fed either a selenium-deficient or selenium
      supplemented diet for 4 wk before mating and then throughout gestation. Rats were
      killed at 21 d of gestation. Selenium deficiency was confirmed by a 95 and 94%
      decrease in glutathione peroxidase and a 84 and 56% decrease in liver type I
      outer ring 5' deiodinase activity in the mother and the fetus, respectively. In
      contrast to the increase in circulating T4 observed in selenium-deficient male
      and nonpregnant female adult rats, serum T4 was not affected by selenium
      deficiency in pregnant rats, but there was a 3-fold increase in serum 3,3',5'
      triiodothyronine concentrations associated with a 70% decrease in maternal brain
      type II outer ring 5' deiodinase activity. Maternal serum 3,5,3'-triiodothyronine
      concentrations were decreased by 21%. Placental 5-deiodinase activity was
      unaffected by selenium deficiency. In the fetus, serum T4, 3,3',5'
      triiodothyronine, and TSH concentrations were not affected by selenium
      deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134169
TI  - Selenium status of very low birth weight infants.
AB  - The selenium (Se) intake and status of 82 very low birth weight infants (birth
      weight 1110 +/- 286 g, gestational age 29.2 +/- 3 wk, mean +/- SD) was assessed
      at 36.3 +/- 3 postconceptional wk, at 40.1 +/- 4 wk (hospital discharge), and at
      3, 6, 9, and 12 +/- 0.75 mo corrected for gestational age. Infants were fed
      formula containing 0.13 mumol/L (10 micrograms/L) Se. Se-dependent glutathione
      peroxidase activity in red blood cells declined corresponding to low Se intakes
      (micrograms/kd/d) for the first 6 mo. With increased consumption of solid foods,
      intakes of dietary Se and Se-dependent glutathione peroxidase activity increased
      at 9 mo, suggesting that the earlier supply of Se was suboptimal. Se-dependent
      glutathione peroxidase activity and intakes of Se were lower in males than in
      females (p < 0.05). We suggest that infant formulas should probably contain 0.26
      0.33 mumol/L (20-25 micrograms/L) Se, particularly those formulas consumed by
      very low birth weight infants.

PMID- 8134170
TI  - Serum transferrin receptor for assessment of iron status in healthy prepubertal
      and early pubertal boys.
AB  - A recently introduced test measures the concentration of transferrin receptor
      (TfR) in serum, which increases shortly after the onset of iron deficiency. In
      adults this increase reflects the degree to which tissue iron availability is
      impaired. We developed a fluoroimmunoassay to quantify TfR. The purpose of this
      study was to evaluate the role of TfR as an index of iron sufficiency in 62
      healthy prepubertal or early pubertal boys. The mean concentration of serum TfR
      was 3.8 (-1 SEM = 3.6, +1 SEM = 3.9) mg/L. No associations were observed between
      the serum TfR and the concentration of Hb, the values of packed cell volume,
      reticulocyte production index, mean corpuscular Hb, mean corpuscular volume, or
      the concentrations of serum iron, transferrin, or ferritin. Because none of the
      subjects had signs of iron deficiency, we determined the 95% reference intervals
      for Hb, red blood cell indices, and the above-mentioned serum concentrations. The
      reticulocyte count and reticulocyte production index were higher than expected.
      Our results indicated that the individual concentration of TfR in serum does not
      depend on any of the several other parameters of iron status in a group of
      healthy individuals.

PMID- 8134171
TI  - Hormonal regulation of hepatitis B virus gene expression: influence of androgen
      receptor.
AB  - Adult HBV-transgenic males produce more hepatitis B surface antigen (HBsAg) in
      serum than females. The difference decreases with castration and is restored with
      testosterone replacement. To investigate the contribution of the androgen
      receptor in this process, HBV-transgenic males were mated with females
      heterozygous for the testicular feminization mutation (Tfm), an X-linked gene
      with 90% reduced androgen receptor. A total of 19 phenotypic HBV-transgenic
      females were studied, of which eight XYTfm females were identified by the
      presence of Y-chromosome DNA using molecular hybridization. The 11 normal (XX)
      females had 11.7 +/- 3.5 micrograms/mL (mean +/- SD) of HBsAg in their serum,
      whereas the Tfm (XY) females had 17.1 +/- 5.9 micrograms/mL (p < 0.05). However,
      the Tfm (XY) females produced less HBsAg than 33 normal (XY) males (41 +/- 12
      micrograms/mL), and the overall ratio of male/female HBsAg levels was reduced:
      XY/XX = 3 versus XYTfm/XX = 1.5. Although dexamethasone caused an increase in
      XYTfm and XX mice, testosterone did not increase HBsAg in XYTfm. These data
      indicate that hepatitis B expression as measured by HBsAg levels in this animal
      model is mediated through an androgen receptor.

PMID- 8134172
TI  - Physiologic levels of uric acid inhibit xanthine oxidase in human plasma.
AB  - Xanthine oxidase, a key source of reactive oxygen species, and purine substrates
      are detected in the circulation after ischemia-reperfusion. High levels of uric
      acid, produced by a xanthine oxidase-catalyzed reaction, are found in human
      plasma. We studied whether uric acid could alter xanthine oxidase activity in
      plasma obtained from eight adults and eight neonates. Known amounts of uric acid
      were added to xanthine and xanthine oxidase-supplemented buffer and plasma, and
      the production of uric acid and superoxide was determined. Uric acid, 150 and 300
      microM, decreased the oxidation of xanthine to uric acid in adult plasma by 37.5
      +/- 5.6 and 48.9 +/- 6.1% and formation of superoxide by 23.2 +/- 1.9 and 32.0 +/
      2.3%, respectively, compared with plasma without uric acid. In newborn plasma, a
      similar pattern and extent of inhibition was observed. Superoxide formation,
      however, was inhibited to a greater extent than in adult plasma. Endogenous
      xanthine oxidase was detected in newborn plasma in nine additional neonates using
      HPLC. These results indicate that uric acid is an effective inhibitor of the
      formation of superoxide and hydrogen peroxide by xanthine oxidase at the levels
      found in human plasma. Plasma uric acid may play an important role in attenuating
      the oxidant-mediated tissue damage caused by xanthine oxidase released into the
      circulation during ischemia-reperfusion.

PMID- 8134173
TI  - Synthesis of alpha 1-antichymotrypsin and alpha 1-antitrypsin by human
      trophoblast.
AB  - alpha 1-Antichymotrypsin (alpha 1-ACHY) and alpha 1-antitrypsin (alpha 1-AT) are
      closely related glycoprotein protease inhibitors, present in plasma and other
      extracellular fluids, that neutralize proteases released by leukocytes in
      response to trauma and inflammatory stimuli. Both inhibitors are synthesized
      primarily by hepatocytes, although lower levels of synthesis by monocytes and
      breast and intestinal epithelial cells have been demonstrated. Recently, the
      immunohistochemical localization of alpha 1-AT and alpha 1-ACHY in intrauterine
      and extrauterine human trophoblastic tissue has been reported. In the present
      study, we have sought to determine whether human trophoblast is also able to
      synthesize alpha 1-AT and alpha 1-ACHY. Messenger RNA for both inhibitors was
      found by Northern blotting in chorionic villi obtained from first trimester and
      term placenta. Substantial differences in messenger levels for both inhibitors
      among individual placentas were noted. alpha 1-ACHY and alpha 1-AT messenger was
      also present in trophoblast cells in primary culture. Synthesis of alpha 1-AT and
      alpha 1-ACHY protein was demonstrated by SDS-PAGE after immunoprecipitation of
      [35S]-labeled alpha 1-AT and alpha 1-ACHY from conditioned media of trophoblast
      cells in culture metabolically labeled with [35S]-methionine. It is of some
      interest that the M(r) of the alpha 1-AT and alpha 1-ACHY secreted by trophoblast
      were 50,000 and 49,000, respectively, compared with 54,000 and 68,000 for these
      proteins in plasma (or secreted by HepG2 human hepatoma and MCF-7 human breast
      cancer cells).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134174
TI  - Colonic acetate in the circulating acetate pool of the infant pig.
AB  - To identify potential sites of acetate utilization and synthesis, we studied the
      contribution of colonic acetate to the circulating acetate pool in six neonatal
      pigs by the simultaneous i.v. infusion of [3H]acetate and colonic infusion of
      [14C]acetate. In the fasting state, the mean (+/- SEM) acetate concentration was
      17 +/- 1 mumol/L in peripheral venous blood, 28 +/- 4 mumol/L in the femoral
      artery, and 46 +/- 4 mumol/L in portal blood. This concentration gradient implies
      that acetate was utilized either by peripheral tissues alone or by both liver and
      peripheral tissues. At the end of the 2-h intracecal acetate infusion, mean
      acetate concentration increased in the femoral artery to 186 +/- 20 mumol/L and
      in the portal vein to 333 +/- 31 mumol/L. In the fasted state, mean acetate
      concentration in the portal vein was on average 63% higher than the acetate
      concentration of the femoral artery, whereas specific radioactivity of the
      [3H]acetate in the portal vein was only 5% of that in the femoral artery. It is
      possible, therefore, that a high proportion of the arterial input of acetate is
      utilized by the portal-drained viscera. Our study identified the gastrointestinal
      tract as an important site of acetate utilization in the fasted state. Further,
      it showed that colonic acetate was efficiently absorbed and utilized in the
      gastrointestinal tract of infant pigs.

PMID- 8134175
TI  - Respiratory mechanics in infants and young children before and after repair of
      left-to-right shunts.
AB  - In an attempt to investigate the relationship between respiratory mechanics and
      pulmonary hemodynamics, we evaluated pulmonary function in 31 infants with left
      to-right shunts and subsequent high pulmonary blood flow, undergoing cardiac
      surgery. Measurements were performed 1 d before and repeated 10 d and 4-5 wk
      after correction. The age of the patients ranged from 4 d to 24 mo, body weight
      from 2.7 to 11.8 kg. Pulmonary artery pressure, assessed by Doppler
      echocardiography, was preoperatively elevated in 23 patients (group 1), whereas
      it was within normal values in eight infants (group 2). Respiratory mechanics
      were measured using the single-breath occlusion technique in sedated infants. To
      evaluate specific compliance, functional residual capacity was determined by
      using an open circuit nitrogen washout technique. A reduced preoperative
      compliance value (mean with 95% confidence interval) was found in group 1: 34.8
      (26.5-43.1) mL.kPa-1. After hemodynamic correction, a progressive significant (p
      < 0.01) improvement was demonstrated at 10 d and 1 mo with values of 47.5 (39.2
      55.8) mL.kPa-1 and 56.5 (45.6-67.4) mL.kPa-1, respectively. A similar trend was
      noted evaluating specific compliance with values of 0.27 (0.24-0.30) kPa-1 and
      0.44 (0.42-0.46) kPa-1, respectively before and after surgery. Preoperative
      functional residual capacity value was 130 (100-160) mL. In group 2, normal
      preoperative compliance values were obtained, without significant changes after
      surgery. In both groups, resistance was within the normal range both before and
      after surgical correction, and functional residual capacity did not change
      either. No correlations were found between compliance and pulmonary artery
      pressure and pulmonary blood flow values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134176
TI  - The formation of alveoli in rat lung during the third and fourth postnatal weeks:
      effect of hyperoxia, dexamethasone, and deferoxamine.
AB  - Terminal gas-exchange units in the lung of many species are, at birth, relatively
      large structures termed saccules. Saccules septate postnatally forming smaller
      units that constitute the final alveoli. In the rat, septation occurs intensively
      during the first 2 postnatal wk after which it has been considered to stop.
      Treatment with dexamethasone or exposure to hyperoxia during the first 2
      postnatal wk markedly inhibits septation as evidenced by the formation of fewer
      and bigger alveoli than in normally developed rats. Deferoxamine, an iron
      chelator, has been reported to protect the lung from the effects of exposure to
      hyperoxia in early postnatal life. In this study, we investigated the effects of
      these treatments during the 3rd and 4th postnatal wk, that is, after the early
      period of rapid alveolarization. Our results show that treatment with
      dexamethasone no longer had any inhibitory effect on alveoli formation; that
      exposure to hyperoxia continued to inhibit the formation of new alveoli,
      resulting in bigger and less numerous alveoli; that treatment of animals exposed
      to hyperoxia with deferoxamine still protected their lungs against hyperoxic
      inhibition; and that elastin fiber length density in the lung was significantly
      reduced in hyperoxic-exposed animals. These results suggest that septation
      continues beyond the 2nd postnatal wk and does not stop abruptly at age 14 d in
      air-breathing rats and that hyperoxic inhibition of alveolarization during the
      3rd and 4th postnatal wk is due to the inhibition of septation of existing or
      newly generated gas-exchange units during that period of lung development.

PMID- 8134177
TI  - Increased expression of human leukocyte antigen-DR on pulmonary macrophages in
      bronchopulmonary dysplasia.
AB  - We used an immunoperoxidase method to examine the expression of the immune
      activation marker HLA-DR on pulmonary tissue obtained at autopsy from 14 patients
      dying of bronchopulmonary dysplasia. Controls consisted of 16 age-matched, sex
      matched children dying of noncardiac, nonrespiratory, noninfectious illnesses or
      as a result of motor vehicle accidents. We did not observe aberrant expression of
      HLA-DR on pulmonary endothelial cells. Positive staining appeared exclusively on
      macrophages. We quantitated the expression of antigen by counting the number of
      positive macrophages and total macrophages/monocytes per high power field.
      Bronchopulmonary dysplasia patients displayed significantly greater numbers of
      both positive and total macrophages compared with the control group (p < 0.05).
      The percent positive macrophages also was significantly higher in the
      bronchopulmonary dysplasia patients (p < 0.005). We also examined a group of
      patients dying with infant respiratory distress syndrome. There was no
      significant difference in number of total macrophages in this group compared with
      age-matched controls.

PMID- 8134178
TI  - Association between protective efficacy of antibodies to tumor necrosis factor
      and suppression of nitric oxide production in neonatal rats with fatal infection.
AB  - In a rat model of fatal infection caused by Pseudomonas aeruginosa, the
      circulating level of nitrite/nitrate (NO2-/NO3-), a good indicator for nitric
      oxide production, was remarkably increased after elevation of circulatory tumor
      necrosis factor (TNF). Anti-TNF MAb cotreatment was shown to blunt hypoglycemia
      and hyperlacticemia and was associated with decreased mortality of septic
      animals. Moreover, anti-TNF MAb significantly reduced not only plasma TNF but
      also plasma NO2-/NO3- levels. Dexamethasone had a similar effects, and when anti
      TNF MAb was used in combination with dexamethasone, the suppression of nitric
      oxide production and the protective efficacy were more remarkable compared with
      therapy with either anti-TNF MAb or dexamethasone alone. Our present data
      suggested that the protective efficacy of anti-TNF MAb may correlate with the
      suppression of nitric oxide production and also with a modulation in metabolic
      abnormalities in the septic newborn rats.

PMID- 8134179
TI  - Oxidant stress responses in premature infants during exposure to hyperoxia.
AB  - To assess oxidant stress responses in newborn infants treated with elevated
      concentrations of oxygen, we measured plasma concentrations of glutathione (GSH)
      and glutathione disulfide (GSSG) in newborn infants ranging from 23 to 42 wk
      gestational age. All infants recruited into the study were mechanically
      ventilated and had catheters placed in their umbilical arteries as part of their
      normal clinical management. Blood samples were obtained on d 1, 3, and 5 and
      weekly thereafter or until the catheters were removed. We observed plasma
      concentrations of GSSG in these infants that were frequently an order of
      magnitude higher than the 0.1 to 0.3 microM we find in adults. Interestingly,
      plasma GSSG concentrations were inversely correlated to the inspired oxygen
      tensions. This effect appeared to arise from the patient selection criteria
      whereby, of the infants studied, those breathing the lowest partial pressures of
      oxygen were the smallest and gestationally youngest. A second observation was
      that plasma concentrations of GSH in the premature infants were substantially,
      indeed often dramatically, lower than we have observed in adult humans (6 to 10
      microM). Finally, we found that in patients with both umbilical arterial and
      umbilical venous catheters arterial GSSG concentrations were consistently higher
      than venous concentrations; conversely, arterial GSH concentrations were lower
      than venous concentrations. The elevated GSSG concentrations we observed in these
      infants indicate marked oxidant stress responses in prematurely born infants,
      even in those infants exposed only to room air. The positive arteriovenous
      gradients of GSSG concentrations across the lungs of these infants suggest that
      at least some of the increased plasma GSSG originates in the lung.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8134180
TI  - Brain superoxide anion generation in asphyxiated piglets and the effect of
      indomethacin at therapeutic dose.
AB  - We have previously shown that generation of superoxide anion occurs in cerebral
      cortex during asphyxia/reventilation in newborn pigs and that a high dose of
      indomethacin (5 mg/kg i.v.) abolishes superoxide anion production. The purposes
      of this study were 1) to determine whether the generation of superoxide anion
      occurs primarily during asphyxia or whether reventilation must take place, 2) to
      investigate the effects of indomethacin pretreatment at a therapeutic dose of 0.2
      mg/kg i.v. on superoxide anion generation, and 3) to investigate the effects of
      oxypurinol, an oxygen free radical scavenger, on superoxide anion production
      during asphyxia/reventilation. Superoxide anion production on cerebral cortex was
      determined by superoxide dismutase-inhibitable nitroblue tetrazolium (NBT)
      reduction using closed cranial windows. Superoxide anion generation during
      asphyxia without reventilation was 4 +/- 2 pmol NBT/mm2 per 20 min, which was
      significantly lower than during asphyxia/reventilation (16 +/- 4 pmol NBT/mm2 per
      20 min) but comparable to the control group (3 +/- 1 pmol NBT/mm2 per 20 min).
      Indomethacin given at therapeutic dosage before asphyxia/reventilation decreased
      superoxide anion production to 3 +/- 1 pmol NBT/mm2 per 20 min, values not
      significantly different from the control group and from piglets pretreated with
      oxypurinol at a dose of 50 mg/kg i.v. (4 +/- 2 pmol NBT/mm2 per 20 min). We
      conclude that in newborn pigs 1) superoxide anions are generated largely during
      reventilation rather than during asphyxia; 2) the therapeutic dose of
      indomethacin (0.2 mg/kg) is effective in inhibiting the superoxide anion
      generation during asphyxia/reventilation; and 3) oxypurinol reduces the
      superoxide anion accumulation on cerebral cortex during asphyxia/reventilation.

PMID- 8134181
TI  - The effect of hypercarbia on age-related changes in cerebral glucose transport
      and glucose-modulated agonal glycolytic rates.
AB  - This study examined the effect of hypercarbia on cerebral agonal glycolytic rates
      and brain lactate accumulation after complete ischemia induced by cardiac arrest.
      Before cardiac arrest, the blood plasma glucose concentration in seven newborn
      (113 d postconception; normal gestation, 115 d) and seven 1-mo-old (144 d
      postconception) piglets was adjusted to a specific value (range, 1 to 64 mM), and
      then inspired ventilation gases were changed to 10:50:40 CO2:O2:N2 for 20 min.
      The agonal glycolytic rate was measured by monitoring the rate of cerebral
      lactate formation in vivo using proton nuclear magnetic resonance spectroscopy,
      and postmortem brain lactate concentrations were measured biochemically in tissue
      extracts obtained 40 to 45 min after cardiac arrest. These data were compared
      with 21 normocarbic piglets of similar age, nine examined as part of the present
      study and 12 examined previously (Corbett RJT, Laptook AR, Ruley JI, Garcia D:
      Pediatr Res 30:579-586, 1991). There was a nonlinear relationship between the
      final postmortem brain lactate concentration and preischemia blood plasma glucose
      concentration that was most prominent in newborn piglets and previously had gone
      unnoticed. When analyzed using a steady-state model for glucose transport, this
      relationship revealed that normocarbic newborns had a lower preischemia affinity
      constant for the transport mechanism for glucose (2.8 +/- 1.5 mM) and lower
      cerebral glucose utilization rate relative to transport rate (0.12 +/- 0.04),
      compared with 1-mo-olds (4.5 +/- 1.4 mM and 0.30 +/- 0.03,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134182
TI  - Possible neuroprotective properties of flunarizine infused after asphyxia in
      fetal lambs are not explained by effects on cerebral blood flow or systemic blood
      pressure.
AB  - Neuroprotective properties of the calcium channel blocker flunarizine have been
      reported after hypoxic-ischemic insults in immature, infant, and adult rats.
      However, its effect on fetal regional cerebral blood flow (rCBF) and systemic
      blood pressure after severe asphyxia is not known. In 15 fetal lambs (3 to 5 d
      after surgery; gestational age at the experiment, 123.2 +/- 2.5 d), arterial
      oxygen content was progressively reduced to 30% by restriction of uterine blood
      flow with an inflatable balloon occluder around the maternal common internal
      iliac artery. The rCBF was measured with radioactive microspheres at baseline
      condition, after 1 h of severe asphyxia, and at 30 and 120 min in the recovery
      phase. Immediately after the end of the occlusion period, fetuses randomly
      received either flunarizine or its solvent (0.5 mg/kg estimated fetal weight). No
      differences in rCBF changes between groups were observed during and after
      asphyxia. Changes in arterial blood pressure or fetal heart rate due to
      flunarizine could not be demonstrated either. Only five fetuses (33%) survived
      this degree of asphyxia longer than 24 h: four of the flunarizine-treated group
      and one of the control group. It is unlikely that this possible protective
      property of the drug is caused by its influence on rCBF, arterial blood pressure,
      or fetal heart rate in the phase immediately after asphyxia.

PMID- 8134183
TI  - Developmental and physiologic changes in cerebral blood flow velocity.
AB  - Developmental change of mean blood flow velocity (MBFV) and resistance index of
      the basilar artery (BA), as well as the changes in MBFV of the BA and the middle
      cerebral artery (MCA) during sleep and hyperventilation, were studied using
      transcranial Doppler sonography in healthy Japanese subjects. The MBFV of the BA
      increased with age from infancy through early childhood, reaching the maximum
      (64.4 +/- 2.6 cm/s) at the age of 5 y, and then gradually decreased. MBFV ratio
      of MCA to BA was almost stable between 1.57 to 1.64 in all age groups. The
      resistance index of the BA showed a maximum value in infants, decreased in 1- to
      2-y-olds, and remained constant thereafter. The MBFV of both the MCA and BA were
      lower during non-rapid eye movement sleep than during wakefulness, whereas during
      rapid eye movement sleep they showed almost the same value as during wakefulness.
      They were also decreased during hyperventilation. At an expiratory CO2 level of
      25 mm Hg (33.33 kPa), the average decrease in MBFV in children (n = 10) was -50.1
      +/- 3.9% in the BA, and -46.2 +/- 7.4% in the MCA, significantly (p < 0.05) more
      marked than that in adults (n = 10) (-41.5 +/- 5.9% and -37.9 +/- 4.2%,
      respectively). Transcranial Doppler sonography is a noninvasive method that has a
      potentially wide range of applications in pediatric neurology.

PMID- 8134184
TI  - Effect of cocaine in early gestation on striatal dopamine and neurotrophic
      activity.
AB  - Prenatal exposure to the dopamine (DA) agonist cocaine, even if limited to early
      gestation, is associated with impaired developmental outcome in the human infant.
      We investigated the possible role of neurotrophic factors in this process by
      evaluating 4- to 6-d-old New Zealand White rabbit pups (n = 14) born to cocaine
      exposed does (30 mg/kg/d s.c. from days 7 to 15 of a 32-d gestation) and control
      does (sterile H2O). Cocaine exposure reduced striatal dopamine by 46% (t = 2.31;
      p < 0.05) and striatal 3,4-dihydroxyphenyl acetic acid by 49% (t = 2.44; p <
      0.05). The number of neuron-specific enolase immunoreactive neurons in
      mesencephalic cultures incubated with striatal extracts from pups exposed to
      cocaine was reduced by 61% relative to the effect of striatal extracts from
      control pups (t = 4.84; p < 0.01). The present results suggest that the reduction
      in striatal dopamine observed may result from a cocaine-induced decrease in
      striatal trophic activity.

PMID- 8134185
TI  - Inhibitor of nitric oxide synthesis reduces hypoxic-ischemic brain damage in the
      neonatal rat.
AB  - We evaluated the neuroprotective effect of the nitric oxide synthesis inhibitor,
      NG-nitro-L-arginine in a neonatal hypoxic-ischemic rat model. Unilateral hypoxic
      ischemic injury was produced in the brain of 7-d-old rats using a combination of
      a common carotid artery ligation and a hypoxic (8% oxygen) exposure for 2.5 h. In
      our experimental condition, rectal temperatures did not differ between NG-nitro-L
      arginine-treated and saline-injected pups. We killed the animals 72 h later and
      assessed the hypoxic-ischemic brain damage histologically. NG-nitro-L-arginine (2
      mg/kg) administered intraperitoneally 1.5 h before hypoxia resulted in 77%
      reduction of the infarcted hemispheric volume and 87% reduction of the infarcted
      striatal volume compared to saline injected controls. NG-nitro-L-arginine given
      1.5 h before the insult also significantly prevented hypoxic-ischemic damage in
      the five hippocampal structures examined, dentate gyrus, CA4, CA3, CA1, and
      subiculum. NG-nitro-L-arginine administered immediately after hypoxia did not
      prevent hypoxic-ischemic brain damage. These results indicate that nitric oxide
      plays a key role in producing neonatal hypoxic-ischemic brain damage.

PMID- 8134186
TI  - Androgen-receptor blockade enhances pulsatile luteinizing hormone production in
      late pubertal males: evidence for a hypothalamic site of physiologic androgen
      feedback action.
AB  - To determine potential mechanisms by which androgens alter gonadotropin secretion
      and elimination in the pubertal male, we administered the potent nonsteroidal
      androgen receptor blocking agent, flutamide, to eight males with Tanner IV or V
      genital development. Venous blood samples were obtained every 10 min for 24 h and
      assayed for LH by a sensitive and high-precision fluorimmunoassay. Subjects were
      studied before and after the administration of flutamide. Deconvolution analysis
      was used to assess specific pulsatile LH secretory characteristics and estimate
      LH production and metabolic clearance rates quantitatively. After antagonism of
      endogenous androgen action, mean 24-h serum LH concentrations increased
      significantly. An increased mean 24-h LH production rate, without evident changes
      in serum LH half-life, accounted for the increase in average serum LH levels. The
      increased daily secretion rate of LH was in turn due to both an augmented mass of
      LH released per secretory episode and increased frequency of secretory events.
      There was no demonstrable change in the maximal rate of LH secretion attained
      within each secretory event. Serum concentrations of total testosterone, free
      testosterone, and 17 beta-estradiol all increased during blockade of androgen
      action. Administration of the antiandrogen had no measurable effect on the
      pituitary response to a single maximally effective dose of exogenous gonadotropin
      releasing hormone (GnRH). These results indicate that, in the late pubertal male,
      endogenous androgen exerts negative feedback control of gonadotropin secretion
      primarily at a hypothalamic site reflected by regulation of the frequency of
      pulsatile LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134187
TI  - Decreased level of epidermal growth factor in milk from diabetic rats.
AB  - Experimental diabetes was induced in rats with streptozocin before mating, and
      the influence of diabetes on epidermal growth factor (EGF) in milk and on other
      milk components was studied. Throughout the lactation period, a significant
      decrease was found both in the production of milk and in the concentration of EGF
      in milk from untreated diabetic rats compared with an insulin-treated diabetic
      group and a control group. Thus, the total output of EGF in milk from diabetic
      rats was considerably decreased. The concentrations of total protein and
      haptocorrin, a cobalamin (vitamin B12)-binding protein, and the content of fat,
      however, were unaltered by diabetes. Therefore, the decrease in milk EGF seemed
      to be selective compared with total protein in milk. The pups of diabetic dams
      had reduced body weights within 1 wk of lactation and reduced body lengths on d
      16 of lactation compared with control pups. Furthermore, the time of eyelid
      opening was delayed, but no difference in the time of tooth eruption was
      observed. Insulin-treatment of diabetic rats restored the milk volume and the EGF
      concentration to values comparable to those of the controls. Pups of the insulin
      treated diabetic dams were comparable to the pups of the controls. These results
      indicate that insulin deficiency in lactating rats causes a decrease in the
      lactational performance and in the EGF content of milk.

PMID- 8134188
TI  - Dietary nucleotides influence lipoprotein metabolism in newborn infants.
AB  - Nucleotide supplementation of adapted-milk formulas may be of interest for infant
      nutrition because nucleotides are involved in the synthesis of proteins and other
      macromolecules such as phospholipids, and thereby facilitate lipoprotein
      synthesis. To determine whether dietary nucleotides influence plasma lipoproteins
      in newborns, we have studied the plasma-lipoprotein concentrations and the
      composition of the major lipoprotein fractions during the first week of life in
      two groups of preterm infants fed formulas differing only in their nucleotide
      content. For comparison, two groups of term infants were studied under the same
      conditions. Lipoproteins were isolated by density ultracentrifugation, and the
      lipid and protein content were determined by standard methods; apolipoprotein A-I
      was determined immunologically. Nucleotide supplementation of formula in preterm
      infants increased all plasma lipoprotein concentrations. In addition, an increase
      in the plasma esterification rate was observed. However, total cholesterol
      concentrations were unchanged. The changes in lipoproteins concentrations were
      due mainly to an increase in apolipoprotein content. Nucleotides added to
      formulas affected term-infants' lipoproteins significantly less than to preterm
      infants. These findings suggest that dietary nucleotides may enhance the
      synthesis of lipoproteins during the early neonatal period, especially in preterm
      infants.

PMID- 8134189
TI  - Influence of lactoferrin on iron absorption from human milk in infants.
AB  - Lactoferrin (Lf) is a major iron (Fe)-binding protein in human milk and has been
      proposed to facilitate Fe absorption. The potential effect of Lf on Fe absorption
      was investigated by measuring Fe absorption in infants fed breast milk (with its
      native content of Lf) and the same milk from which Lf had been removed (> 97%) by
      treatment with heparin-Sepharose. Eight breast-fed infants (2-10 mo; mean age 5
      mo) were fed 700 to 1000 g of each milk in a randomized, cross-over design with
      each child acting as his/her own control. The milk was labeled with 8.6 mumol
      (0.5 mg) of 58Fe and Fe absorption was measured by quantifying the incorporation
      of the isotope into red blood cells 14 d after intake using thermal ionization
      mass spectrometry. Fractional Fe absorption was significantly lower (p < 0.05)
      from breast milk than from Lf-free breast milk. The geometric mean (range) was
      11.8% (3.4-37.4%) for breast milk and 19.8% (8.4-72.8%) for Lf-free breast milk.
      These results do not support a direct role for Lf in the enhancement of Fe
      absorption from human milk at this age. In addition, Fe absorption (11.8%) from
      human milk fed over several feeds was lower than that previously reported for
      single feed studies.

PMID- 8134190
TI  - Prevention of postnatal bone demineralization in very low-birth-weight infants by
      individually monitored supplementation with calcium and phosphorus.
AB  - Preterm infants are more prone to bone mineral deficiency the lower their birth
      weight. To achieve the intrauterine bone mineral accretion rate postnatally, 74
      low-birth-weight infants (median birth weight, 980 g; range 430-1.580 g) were
      each supplemented enterally and/or parenterally with calcium and/or phosphorus in
      gradually increased amounts. The aim was to yield a simultaneous urinary
      excretion of Ca and inorganic phosphorus (Pi) at low concentrations (1-2 mmol/L)
      in spot urine specimens taken twice weekly. The hypothesis was that the
      intrauterine mineralization rate (4.5 mg cm-1/100 g weight gain) would be
      achieved postnatally in very low-birth-weight infants, if they were supplemented
      with enough Ca and/or Pi to effect at least a low (1-2 mmol/L) simultaneous
      urinary excretion of both ions, as compared with infants who do not excrete both
      ions and would accrete the bone minerals at a lower rate. The change in bone
      mineral content was measured by single photonabsorption densitometry and related
      to weight gain during periods of 2 to 6 wk. Infants who simultaneously excreted
      Ca (> 1.2 mmol/L) + Pi (> 0.4 mmol/L) in more than half of the urine samples
      retrospectively showed the highest bone mineral accretion, 5.1 mg cm-1/100 g
      weight gain, which was equivalent to the fetal mineralization rate (4.5). In this
      group the bone mineral status significantly contributed to the variance of the
      bone mineral accretion rate; severely demineralized infants showed a catch-up
      mineralization. A significantly lower rate (2.4) was observed in infants who
      excreted Ca+Pi in less than half of the urinary samples.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8134191
TI  - Influence of fetal gender on the concentration of interleukin-1 receptor
      antagonist in amniotic fluid and in newborn urine.
AB  - IL-1 receptor antagonist (IL-1ra) is a cytokine that blocks the effects of IL-1
      by binding to IL-1 receptors without inducing signal transduction. Amniotic fluid
      contains high concentrations of IL-1ra. The purpose of this study was 1) to
      analyze whether factors related to the mother or the fetus influence amniotic
      fluid IL-1ra concentration, and 2) to study whether the fetus is a source of IL
      1ra. Two hundred two specimens of amniotic fluid, as well as 21 urine samples
      from newborn infants, were analyzed. Women carrying a female fetus had a higher
      concentration of amniotic fluid IL-1ra than those carrying a male fetus (female
      136.4 +/- 6.1 micrograms/L, n = 83; male 74.7 +/- 3.7 micrograms/L, n = 119; p <
      0.0001, unpaired two-sided t test). Length of gestation, presence or absence of
      labor signs, or elevated IL-1 beta in amniotic fluid did not affect the
      concentration of IL-1ra in amniotic fluid. Urine of infants taken during the
      first 48 h of life contained a high concentration of IL-1ra (91.1 +/- 17.5
      micrograms/L). The urinary IL-1ra concentration was higher in female newborns
      than in male newborns (females 124.0 +/- 25.2 micrograms/L, n = 11; males 54.9 +/
      19.1 micrograms/L, n = 10; p = 0.04). We conclude that 1) the concentration of
      IL-1ra in amniotic fluid and newborn urine is dependent on the gender of the
      fetus and of the newborn and 2) fetal urine is a major source of amniotic fluid
      IL-1ra.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134192
TI  - Nitric oxide reverses acute hypoxic pulmonary hypertension in the newborn piglet.
AB  - Inhaled nitric oxide has been reported to act as a specific pulmonary
      vasodilator. We used the newborn piglet to create acute hypoxic pulmonary
      hypertension and examined the effect of inhaled nitric oxide in this model. Six
      newborn piglets were instrumented in order to measure cardiac index, pulmonary
      arterial pressure, and systemic arterial pressure. Pulmonary hypertension was
      induced by reducing the fraction of inspired oxygen to 0.12 to 0.14. With hypoxia
      (arterial oxygen saturation between 35 and 45%), pulmonary arterial pressure
      increased by 48% (p < 0.01), pulmonary vascular resistance increased by 74% (p <
      0.01), and both systemic arterial pressure and systemic vascular resistance
      decreased by 38 and 31%, respectively (p < 0.01). The animals were then giving
      varying concentrations of inhaled nitric oxide between 5 and 80 parts per million
      in random order. All concentrations of nitric oxide were associated with a rapid
      decrease in pulmonary arterial pressure and pulmonary vascular resistance (p <
      0.001). Cardiac index increased (p < 0.001) and systemic vascular resistance
      significantly decreased (p = 0.01) with all doses of inhaled nitric oxide. The
      ratio of pulmonary to systemic vascular resistance decreased with all levels of
      inhaled nitric oxide (p < 0.001). For all of the above observations there was no
      significant difference noted between the varying doses of nitric oxide. The time
      course of the pulmonary arterial pressure response to nitric oxide was
      approximately twice as fast as that seen with the inhalation of 100% oxygen (10,
      50, 90% responses of 4.1, 8.8, 88.6 versus 6.7, 51.9, 197 s, respectively; p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134193
TI  - The effect of inhaled nitric oxide on the pulmonary circulation of the neonatal
      pig.
AB  - To study the pulmonary vasodilator selectivity of low levels of inhaled nitric
      oxide (NO) in a model of neonatal pulmonary hypertension, we sequentially exposed
      anesthetized, spontaneously breathing neonatal pigs to each of four different
      inspired gas mixtures: room air, room air with 25 parts per million NO, hypoxia
      (14% O2 in N2), and hypoxia with 25 parts per million NO. The room air, room air
      with NO, hypoxia, and hypoxia with NO exposures were of 15-min duration. The
      following measurements were made: mean systemic arterial, mean pulmonary
      arterial, and wedge pressures; thermodilution cardiac output; esophageal
      pressure; tracheal flow; and arterial PO2, PCO2, pH, hemoglobin, and
      methemoglobin. Inhalation of NO decreased pulmonary arterial pressure in both
      room air and hypoxia conditions (mean pulmonary arterial pressure 16 +/- 1 torr
      room air, 13 +/- 1 torr room air with NO, p < 0.005; and mean pulmonary arterial
      pressure 21 +/- 2 torr hypoxia, 14 +/- 1 torr hypoxia with NO, p < 0.005). NO had
      no significant effect on systemic arterial pressure, cardiac output, dynamic lung
      compliance, pulmonary resistance, or the measured blood variables during either
      control or hypoxic conditions. The results indicate that inhaled NO was a
      selective pulmonary vasodilator that could effectively reverse acute hypoxic
      pulmonary vasoconstriction. The normoxic vasodilation produced by NO inhalation
      also indicates the existence of basal vasomotor tone in the anesthetized,
      spontaneously breathing neonatal pig. The short-term exposures used produced no
      detectable manifestations of toxic side effects.

PMID- 8134194
TI  - The vascular site of action of hypoxia in the neonatal pig lung.
AB  - To determine the vascular site(s) of action of hypoxia in the neonatal pig,
      isolated lungs were perfused at a constant flow rate and left atrial pressure;
      arterial, venous, and double occlusions were performed. The distribution of the
      total pulmonary vascular resistance and the total dynamic vascular compliance
      were calculated using a model of the pulmonary circulation consisting of
      upstream, central, and downstream compliances and resistances upstream and
      downstream of central compliance. In addition, the static vascular compliance was
      measured by venous followed by arterial occlusion, and the total vascular volume
      was measured by dye-dilution. In this preparation during control conditions
      alveolar PO2 = 12 +/- 2 kPa), total pulmonary vascular resistance was nearly
      evenly divided between resistance upstream and downstream of double occlusion
      pressure and total dynamic vascular compliance was concentrated mainly in the
      central compliance (7% upstream compliance, 82% central compliance, and 11%
      downstream compliance). Hypoxia (alveolar PO2 = 4 +/- 1 kPa) increased both
      resistance upstream of double occlusion pressure (p < 0.005) and resistance
      downstream of double occlusion pressure (p < 0.02) and decreased central
      compliance (p < 0.005). Hypoxia also decreased total pulmonary blood volume (p <
      0.02). These results suggest that in the pulmonary vasculature of the neonatal
      pig, hypoxia results mainly in 1) arterial constriction as evidenced by a large
      increase in upstream resistance and a decrease in total pulmonary blood volume
      and 2) a smaller but significant venous constriction. This venous constriction
      may have implications in the pathogenesis and therapy of pulmonary vascular
      diseases associated with hypoxia such as postasphyxial lung disease and
      bronchopulmonary dysplasia.

PMID- 8134195
TI  - Effect of methionine and nitrous oxide on homocysteine export and remethylation
      in fibroblasts from cystathionine synthase-deficient, cb1G, and cb1E patients.
AB  - We investigated the nitrous oxide-induced inactivation of methionine synthase and
      the concurrent homocysteine (Hcy) export in mutant fibroblasts with defects in
      the homocysteine catabolizing enzyme, cystathionine beta-synthase, or in
      methionine synthase, which carries out homocysteine remethylation. The
      fibroblasts were incubated in various concentrations of methionine to create
      conditions favoring methionine conservation or catabolism. In cystathionine beta
      synthase-deficient cells, high medium methionine partly protected the enzyme
      against inactivation, as previously found in normal fibroblasts. The Hcy export
      rate at low methionine levels was low (0.2-0.6 nmol/h/10(6) cells), and increased
      2-3-fold at high methionine levels. Nitrous oxide enhanced Hcy export rate at low
      methionine, so that in the presence of nitrous oxide, the Hcy export became less
      dependent of methionine. In cb1G cells, the enzyme inactivation was moderate and
      independent of medium methionine. The Hcy export rate was intermediate (0.5-0.8
      nmol/h/10(6) cells) at low methionine levels, and increased moderately (< 2-fold)
      at high methionine levels or following nitrous oxide exposure. In cb1E mutants,
      the enzyme activity was not affected by nitrous oxide, and the Hcy export was
      high (0.8-1.6 nmol/h/10(6) cells) and independent of methionine and nitrous
      oxide. These data suggest that Hcy remethylation and cystathionine beta-synthase
      activity are major determinants of Hcy export at low and high methionine,
      respectively. The low susceptibility of methionine synthase to nitrous oxide in
      the presence of high methionine or in cb1G or cb1E mutants is probably related to
      low catalytic turnover.

PMID- 8134196
TI  - Prenatal exposure to epidermal growth factor attenuates respiratory distress
      syndrome in rhesus infants.
AB  - Treatment of nonhuman primate fetuses with epidermal growth factor (EGF) results
      in histologic and biochemical maturation of their lungs. To determine whether
      these effects improve lung function postnatally, we studied premature rhesus
      infants delivered at 78% of gestation after in utero treatment with EGF (n = 5)
      or placebo (n = 5). Indices of lung function during the 4 d of postnatal care
      included fractional concentration of inspired oxygen, peak inspiratory pressure,
      ventilator rate, mean airway pressure, arterial to alveolar oxygen tension ratio,
      and ventilation index. Statistically significant differences were noted in the
      time courses of these variables between EGF- and placebo-treated infants. The
      direction of the differences indicated that the EGF-treated infants had less
      severe lung disease. Surfactant apoprotein A concentration and lecithin to
      sphingomyelin ratio were both significantly higher in the amniotic fluid of the
      EGF-treated group, indicating advanced biochemical maturation in this group of
      animals. Whereas birth weight was not affected by EGF exposure, adrenal and gut
      weights, standardized for body weight, were increased significantly. Histologic
      studies showed advanced cellular maturation with increased parenchymal airspace
      and decreased parenchymal tissue space in the EGF-treated group compared with the
      control group. We conclude that prenatal exposure to EGF stimulates biochemical
      and histologic maturation of the lung and markedly attenuates the clinical
      severity of respiratory disease in this model of simian respiratory distress
      syndrome.

PMID- 8134197
TI  - Pharmacologic interactions of exogenous lung surfactant and recombinant human
      Cu/Zn superoxide dismutase.
AB  - The effect of exogenous surfactant on the pharmacokinetics of intratracheally
      administered recombinant human superoxide dismutase (rhSOD) was studied. Five
      groups of rats received the following intratracheally: 1 mL/kg of saline; 5 or 25
      mg/kg of rhSOD; or 4 mL/kg of exogenous surfactant followed in 30 min by 5 or 25
      mg/kg of rhSOD. Animals were killed at 24, 48, and 72 h, and serum,
      bronchoalveolar lavage, and lung tissue were analyzed for rhSOD. rhSOD was not
      detected in the lungs of saline-treated animals or in serum from any animals. At
      24 h, lung-tissue rhSOD was higher in rats treated with surfactant and rhSOD
      versus rhSOD alone (5 mg/kg: 6.8 +/- 2.5 versus 0 microgram/whole lung, p < 0.05;
      25 mg/kg: 29.9 +/- 9.6 versus 0.1 +/- 0.1 microgram/whole lung, p < 0.05).
      Bronchoalveolar lavage fluid levels correlated well with lung tissue
      concentrations. By 48 h, lung tissue rhSOD concentrations were insignificant in
      all groups. rhSOD was still present in lavage fluid from rats treated with
      surfactant and rhSOD. No rhSOD was detected at 72 h. In separate in vitro
      experiments, physical and biological drug-drug interaction studies were
      performed. When radiolabeled rhSOD was combined with exogenous surfactant and
      centrifuged at 10,000 x g for 30 min, 81.3 +/- 2.5% of rhSOD was found in the
      supernatant versus 18.7 +/- 2.5% in the surfactant pellet. Serial washing of the
      surfactant pellet removed virtually all remaining rhSOD. This finding suggests
      that the rhSOD and surfactant were only weakly associated. Combining rhSOD and
      exogenous surfactant did not alter the activity of either agent.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8134198
TI  - Expression of manganese superoxide dismutase in ovine kidney cortex during
      development.
AB  - Manganese superoxide dismutase (MnSOD) is one of the main antioxidant enzymes in
      mammalian tissue. Previous studies have shown that the activity of MnSOD
      increases in the rat kidney during development. To define further the
      developmental change in MnSOD activity and better understand some of the steps
      involved in the control of MnSOD expression during kidney development, we
      measured MnSOD messenger RNA and enzyme activity in the ovine kidney cortex
      during fetal life, in the newborn period, and in adults. MnSOD mRNA and enzyme
      activity were detected at 0.65 gestation. Hybridization of the Northern blot with
      a human MnSOD cDNA probe showed evidence of two transcripts of 4.0 and 1.5 kb,
      respectively. There was a significant increase with age of MnSOD activity and
      MnSOD mRNA (p < 0.0001). The abundance of each MnSOD transcript significantly
      increased with age (p < 0.001). In the fetuses, both transcripts increase in
      parallel; in newborns and adults the 1.5-kb increase was significantly greater
      than the 4.0-kb increase. Enzyme activity and mRNA were strongly correlated (r =
      0.89, p < 0.0001). These data indicate that the expression of MnSOD is
      developmentally regulated in the ovine kidney cortex. This increase seems to be
      dependent largely on pretranslational events.

PMID- 8134199
TI  - The relationship between cerebral blood flow velocity fluctuations and sleep
      state in normal newborns.
AB  - Cerebral blood flow velocity was recorded for an average of 23 4-min epochs
      during natural sleep in 11 normal full-term newborn babies. Intracranial
      pressure, core temperature, and respiration were simultaneously and non
      invasively monitored. Sleep state was classified using information from EEG,
      pattern of respiration, and eye and body movements by a trained observer. From a
      total of 238 epochs, 66 were considered to occur in quiet sleep, 101 in active
      sleep, and in 77 the baby was awake, in a transitional state or moving
      excessively. Slow cyclical variations in cerebral blood flow velocity were
      observed with a frequency of between 2 and 6 cycles/min, and these were of
      significantly greater amplitude during quiet sleep (24%) compared to active sleep
      (16%; p < 0.0001, Mann Whitney U test). There was no difference in median
      cerebral blood flow velocity (7.5 cm/s). The cyclical variation observed in
      normal babies were similar to those described in preterm babies and adults, at a
      similar frequency to B waves in intracranial pressure. They may represent
      vasomotor waves in the small autoregulatory arteries of the brain. Reduction in
      sensitivity of the receptors initiating the waves may occur in active sleep or
      there may be competition from other oscillatory mechanisms.

PMID- 8134200
TI  - Postnatal maturation of the response of the canine sinus node to critically
      timed, brief vagal stimulation.
AB  - We have previously demonstrated that vagal phase-response curves (PRC), which
      characterize the effects of critically timed, brief vagal stimuli on sinus node
      automaticity, exhibit a fundamentally different shape in the canine newborn than
      in the adult. In this study we analyzed the changes in sinus cycle length in
      response to critically timed, brief vagal stimuli, delivered to the decentralized
      cervical right and left vagosympathetic trunks, in two older age groups: 14 1-mo
      old puppies (ages 21-36 d), and eight 2-mo-old puppies (ages 56-62 d). Vagal PRC
      were constructed by plotting the magnitude (percent change) of the vagal
      chronotropic response as a function of the phase of the cardiac cycle at which
      the vagus nerve was stimulated. At 1 mo of age adult-type PRC were observed, but
      in only six of the puppies (43%) and only in response to right vagal stimulation.
      By 2 mo of age adult-type PRC were observed in seven of eight puppies (88%) in
      response to right vagal stimulation and in three of eight (38%) in response to
      left vagal stimulation. Thus, clear developmental changes in the phase dependence
      of the vagal chronotropic response can be tracked over the first 2 mo of life in
      the dog.

PMID- 8134201
TI  - Escherichia coli endotoxin depresses left ventricular contractility in neonatal
      lambs.
AB  - We evaluated the effects of Escherichia coli endotoxin on the peripheral vascular
      hemodynamics and myocardial function of the newborn lamb to understand how gram
      negative endotoxemia can lead to cardiovascular collapse in newborn infants.
      Fifteen lambs, 0-3 d old, were acutely instrumented with a micromanometer-tipped
      catheter and two pairs of ultrasonic crystals to measure left ventricular (LV)
      pressure and LV anterior-posterior and septal-free wall dimensions, a fluid
      filled catheter for monitoring aortic pressure, and an electromagnetic flow probe
      to measure systemic blood flow. Cardiovascular performance was evaluated by
      measuring or deriving the following variables: mean arterial blood pressure
      (MABP), LV pressure, heart rate, stroke volume, systemic vascular resistance, LV
      dp/dt, end-diastolic area, arterial elastance, and end-systolic elastance (the
      slope of the end-systolic pressure-area relationship) as an index of
      contractility independent of loading conditions and heart rate. Once
      instrumented, nine lambs received endotoxin, 0.5 mg/kg i.v., and six animals,
      serving as controls, received a saline infusion. Of the endotoxin-treated lambs,
      five survived the duration of the study (120 min from the beginning of the
      endotoxin infusion), and four died by 90 min from the beginning of the endotoxin
      infusion. No significant changes in any of the cardiovascular variables occurred
      in the control group. A significant decrease in MABP was seen in all endotoxin
      treated animals by 45 min after the beginning of the endotoxin infusion. MABP
      decreased by 52% from baseline in the survivors and 38% in the nonsurvivors. In
      the survivors, the MABP stabilized with saline boluses, whereas in the
      nonsurvivors MABP continued to decrease until death.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8134202
TI  - Tissue-specific Fc gamma and complement receptor expression by alveolar
      macrophages determines relative importance of IgG and complement in promoting
      phagocytosis of Pseudomonas aeruginosa.
AB  - Because the expression of IgG Fc receptors and complement receptors on
      macrophages may vary in a tissue-specific manner, we used monoclonal antibodies
      and flow cytometry to define the expression and function of opsonin receptors on
      fresh normal and cystic fibrosis (CF) bronchoalveolar lavage (BAL) macrophages.
      Using flow cytometry to separately analyze individual types of cells, we then
      determined the relative contributions of IgG and complement to phagocytosis of
      Pseudomonas aeruginosa by fresh BAL cells, avoiding alterations in receptor
      expression due to in vitro purification or culturing techniques. Neither normal
      nor CF BAL macrophages express appreciable amounts of the complement receptors
      CR1, CR2, or CR3. These results were confirmed by immunohistochemical staining of
      fixed lung sections. BAL macrophages express a high-affinity IgG receptor, Fc
      gamma RI, that is not found on neutrophils (PMN). In contrast, chemoattractant
      stimulated blood PMN express large amounts of CR1 and CR3 but do not express Fc
      gamma RI. These results correlate with phagocytosis assays, which show that
      phagocytosis by macrophages is enhanced by relatively low concentrations of IgG
      but that the addition of complement does not further increase their phagocytosis.
      In contrast, low concentrations of IgG alone do not promote phagocytosis by PMN,
      whereas addition of complement markedly enhances phagocytosis by PMN. These
      results may explain the previously reported sensitivity of macrophages rather
      than PMN to the "blocking" effects of anti-Pseudomonas antibodies from CF
      patients, and emphasize the pathologic significance of interference with IgG and
      complement mediated opsonization in the lung in CF.

PMID- 8134203
TI  - Heparin therapy in pediatric patients: a prospective cohort study.
AB  - Current guidelines for heparin therapy in pediatric patients have been
      extrapolated from trials in adult patients without rigorous evaluation of
      efficacy and safety. We prospectively monitored consecutive pediatric patients
      receiving systemic doses of heparin over 10 mo at one institution using a
      predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive
      children; 38 males and 27 females, received systemic doses of heparin. Thirty
      children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial
      thrombi, most frequently after diagnostic angiography; and the remaining 24
      received heparin prophylactically, for congenital heart disease. Twenty-nine
      (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or
      older. Congenital heart disease was the predominant diagnosis under 1 y and deep
      venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of
      children (n = 30) achieved a minimal level activated partial thromboplastin time
      (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and
      81% by 48 h. For all 65 children, APTT values were within the therapeutic range
      43% of the time. APTT values outside the therapeutic range were twice as likely
      to be low as high. The average amount of heparin required to maintain therapeutic
      APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h
      for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic
      disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8134204
TI  - Inhibition of iodothyronine 5'-deiodinase by iopanoic acid does not block nuclear
      T3 accumulation during rat fetal development.
AB  - We studied the effect of iopanoic acid (IOP), an iodinated contrast medium, on
      iodothyronine 5'-deiodinase (5'D) and nuclear T3 content (nT3) in fetal tissues.
      In 18- and 20 day-old fetuses from control dams, nT3 was higher in interscapular
      brown adipose tissue (IBAT, 69 +/- 5 and 281 +/- 8 fmol/mg of DNA) than in brain
      (16 +/- 2 and 42 +/- 3 fmol/mg of DNA) or liver (5.6 +/- 1 and 27 +/- 2 fmol/mg
      of DNA). IOP administration (10 mg, twice daily) to pregnant rats on days 18 and
      19 postconception significantly blocked 5'D activity in fetal IBAT and brain at
      day 20. Liver 5'D was not affected. The rise in nT3 was not modified by IOP
      treatment in IBAT, but it was enhanced in brain and liver of IOP-treated fetuses
      on day 20. In contrast, in adult rats, IOP treatment reduced IBAT nT3.
      Prolongation of IOP treatment until day 21 decreased fetal body weight on day 22
      and inhibited IBAT 5'D. No change was produced in mitochondrial oxidative
      capacity, the subunit II of cytochrome oxidase, or uncoupling protein mRNA
      expression in IBAT from IOP-treated fetuses. Thus, the finding that IOP does not
      decrease the nT3 of fetal IBAT explains the lack of effect of IOP on uncoupling
      protein expression in fetuses, in contrast with the known decrease in adults.
      Present results also show that IOP increases nT3 in brain and liver, indicating a
      general incapacity of IOP to decrease nT3 in fetal tissues. It is concluded that
      the effects of IOP during fetal life differ from those in adults.

PMID- 8134205
TI  - Intravenous L-carnitine and acetyl-L-carnitine in medium-chain acyl-coenzyme A
      dehydrogenase deficiency and isovaleric acidemia.
AB  - The purpose of this study was to determine whether treatment with L-carnitine or
      acetyl-L-carnitine enhances the turnover of lipid or branched-chain amino acid
      oxidation in patients with inborn errors of metabolism. Increasing i.v. doses of
      L-carnitine and acetyl-L-carnitine were given to one patient with medium-chain
      acyl-CoA dehydrogenase deficiency and to another with isovaleric acidemia. Both
      patients were in stable condition and receiving oral L-carnitine supplements. The
      excretion of carnitine and disease-specific metabolites was measured. The
      incorporation of L-carnitine in the intracellular pool was demonstrated using
      stable isotopes and mass spectrometry. Increasing doses of either i.v. L
      carnitine or acetyl-L-carnitine did not stimulate the excretion of
      octanoylcarnitine in the patient with medium-chain acyl-CoA dehydrogenase
      deficiency, nor did it raise the plasma levels of either cis-4-decenoate or
      octanoylcarnitine. Similarly, increasing doses of either i.v. L-carnitine or
      acetyl-L-carnitine did not enhance the excretion of isovalerylcarnitine in a
      patient with isovaleric acidemia. The excretion of isovalerylglycine actually
      decreased. We conclude that there was no evidence of enhanced fatty acid beta
      oxidation or enhanced branched-chain amino acid oxidation in vivo by the
      administration of high doses of L-carnitine or acetyl-L-carnitine in these two
      patients. Because only one individual with each disorder was studied, the data
      are only indicative and may not necessarily be representative of all individuals
      with these disorders. Definite settlement of this issue will require further
      studies in additional subjects.

PMID- 8134206
TI  - Low-dose indomethacin and prevention of intraventricular hemorrhage: a
      multicenter randomized trial.
AB  - OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a
      major risk factor for neurodevelopmental handicap in very low birth weight
      neonates. Previous trials have suggested that indomethacin would lower the
      incidence and severity of IVH in very low birth weight neonates. METHODS: We
      enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at
      6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to
      test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to
      12 postnatal hours and every 24 hours for two more doses) would lower the
      incidence and severity of IVH. Serial cranial ultrasound examinations and
      echocardiographs were performed. RESULTS: There were no differences in the birth
      weight, gestational age, sex, Apgar scores, and percent of neonates treated with
      surfactant between the indomethacin and placebo groups. Within the first 5 days,
      25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH
      (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4
      IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin
      treated neonates and 29 control neonates died (P = .08); there was a difference
      favoring indomethacin with respect to survival time (P = .06). Eighty-six percent
      of all neonates had a patent ductus arteriosus on the first postnatal day;
      indomethacin was associated with significant ductal closure by the fifth day of
      life (P < .001). There were no differences in adverse events attributed to
      indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic
      indomethacin significantly lowers the incidence and severity of IVH, particularly
      the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus
      arteriosus and is not associated with significant adverse drug events in very low
      birth weight neonates.

PMID- 8134207
TI  - Video game-related seizures: a report on 10 patients and a review of the
      literature.
AB  - OBJECTIVE: To further describe the features, postulated pathophysiology,
      treatment, and outcome of seizures occurring while playing or watching video
      games (video game-related seizures (VGRS)). DESIGN: We evaluated retrospectively
      10 patients with VGRS seen by us and reviewed 25 reported cases. RESULTS: The 35
      patients ranged in age from 1 to 36 years (mean: 13.2); and 26 subjects (74%)
      were male. Eight individuals (29%) had prior infrequent nonfebrile seizures, 4
      (11%) had febrile convulsions, and 2 (6%) had a family history of epilepsy. VGRS
      consisted of generalized tonic-clonic seizures in 22 of 35 individuals (63%);
      absences in 2 (6%); simple partial seizures in 6 (19%); complex partial seizures
      in 4 (11%); and other manifestations in 4. Neurologic examination and computed
      tomographic and magnetic resonance imaging scans were normal.
      Electroencephalograms demonstrated generalized or focal, interictal or ictal
      epileptic patterns in 11 of 21 patients (52%) and photoparoxysmal responses in 17
      of 32 (53%). Eleven of 15 individuals (73%) treated with video game (VG)
      abstinence alone, 3 of 6 who received anticonvulsants but played VGs, and 7 of 12
      treated with combined VG abstinence and anticonvulsants had no further seizures.
      CONCLUSIONS: We postulate that a special convulsive susceptibility of selected
      neurons in striate, peristriate, infratemporal, and posterior parietal cortices
      to particular visual stimuli plays a major role in VGRS. VG abstinence is the
      treatment of choice of VGRS. Anticonvulsant medication is suggested only for
      those individuals who continue to play VGs or suffer from seizures triggered by
      other, unavoidable visual stimuli, or from unprovoked attacks.

PMID- 8134208
TI  - Neurologic manifestations of cocaine exposure in childhood.
AB  - OBJECTIVE: To describe the neurologic manifestations of cocaine exposure in
      children and adolescents as the neurologic effects of cocaine have been described
      in adults and neonates. METHODS: During 1-year period, 41 children between the
      ages of 2 months and 18 years who had been exposed to cocaine, were examined in
      the emergency department at the Children's National Medical Center. Cocaine
      exposure was documented on urine samples; all were confirmed by urine gas
      chromatographic/mass spectrometric analysis. RESULTS: Nineteen (46%) of 41 had
      neurologic abnormalities, including seizures (7), obtundation (6), delirium (4),
      dizziness (1), drooling (1), and ataxia (1). In 14 others, the neurologic effects
      of cocaine were difficult to determine because of other concomitant medical
      conditions, including head injuries and severe abdominal or chest trauma. Two
      major age-related patterns were seen: (a) in each child < 5 years of age,
      seizures and obtundation; and (b) in 11 older children, delirium (3), dizziness
      (1), drooling (2), and lethargy (4). Seizures, occurring at ages 12 months to 8
      years, were focal with secondary generalization in three and generalized in four.
      They were associated with fever in two children. Six children had no further
      seizures, and one developed a mixed-seizure disorder. Passive intoxication while
      being in a room in which "crack" was smoked was the most likely cause of exposure
      for young victims. Multiple drug abuse was not documented in any child with
      neurologic impairment. CONCLUSIONS: 1) Cocaine exposure is common in children in
      our urban setting; 2) neurologic manifestations frequently occur; 3) in children
      8 years of age or younger, "passive" ingestion/inhalation is associated with
      focal and generalized seizures without evidence of structural brain injury; 4)
      cocaine may lower seizure threshold in children predisposed to seizures; 5) in
      children > 8 years of age, manifestations are similar to those in adults; 6)
      trauma and motor vehicle accidents were seen in the adolescent age group exposed
      to cocaine; and 7) urine toxicological study in cocaine exposure is recommended
      in all first-time seizures as well as first-time febrile seizures.

PMID- 8134209
TI  - Smoking and health in substance-abusing adolescents: a two-year follow-up.
AB  - OBJECTIVE: To examine the prevalence and persistence of cigarette smoking along
      with health outcomes in a clinical sample of substance-abusing adolescents.
      DESIGN: This is a 2-year prospective case series study. SETTING: Subjects were
      recruited from two private, hospital-based inpatient adolescent substance abuse
      treatment facilities. PARTICIPANTS: A consecutive sample of 166 adolescents, ages
      12 to 18, meeting Diagnostic and Statistical Manual of Mental Disorders (3rd ed,
      revised) criteria for substance abuse participated in the present investigation.
      Of the original sample, 154 and 144 were interviewed 12 and 24 months after
      discharge, respectively. MEASUREMENT AND RESULTS: Information regarding cigarette
      smoking, drug and alcohol use, and respiratory problems was based on self-report
      by the adolescents and was corroborated by parent interview. The prevalence of
      smoking in this sample of teens immediately before treatment was 85%. Sixty-one
      percent of the sample smoked 1/2 pack or more/day and 75% were daily smokers.
      Although prevalence (74 and 77%) and average daily cigarette consumption (11.1
      and 10.7 cigarettes daily) decreased at 12 and 24 months after treatment, rates
      remained very high. Teens reporting posttreatment respiratory problems smoked
      more, and heavier smokers at the time of treatment were more likely to report
      respiratory problems at follow-up than lighter smokers. CONCLUSIONS: Substance
      abusing teens smoke at rates far and above those of the general adolescent
      population. Further, these teens appear at increased risk for negative health
      consequences regardless of posttreatment drug and alcohol use. These findings
      highlight the importance of preventing adolescent cigarette smoking by substance
      abuse treatment programs.

PMID- 8134210
TI  - The Seattle children's bicycle helmet campaign: changes in helmet use and head
      injury admissions.
AB  - OBJECTIVE: To describe the impact of a community bicycle helmet campaign on
      helmet use and the incidence of bicycle-related head injuries. SETTING:
      Metropolitan community and a large health maintenance organization.
      INTERVENTIONS: Communitywide bicycle helmet campaign. OUTCOMES: Rate of observed
      bicycle helmet use in the community and incidence of bicycle-related injuries in
      an health maintenance organization population. RESULTS: Helmet use among school
      aged children increased from 5.5% in 1987 to 40.2% in 1992. Bicycle-related head
      injuries decreased by 66.6% in 5- to 9-year-old and 67.6% in 10- to 14-year-old
      members of an health maintenance organization. CONCLUSIONS: Educational campaigns
      can increase helmet use and decrease the incidence of bicycle-related head
      injury.

PMID- 8134211
TI  - A comparison of risky health behaviors of sexually active, sexually abused, and
      abstaining adolescents.
AB  - OBJECTIVE: To report on rates of sexual abuse among a normative sample of
      adolescents and identify psychosocial correlates associated with sexual abuse.
      METHOD: An anonymous self-report survey examining an array of psychosocial items
      to which 3448 grade 8 and 10 students from rural and metropolitan school
      districts in a southern state responded. RESULTS: There was a 105 rate of sexual
      abuse among this normative sample. Victims of forced sex were disproportionately
      female and African-American, and were more likely to reside in single-parent
      households. These sexually abused girls reported significantly higher levels of
      risky health behaviors and risky attitudes on 11 (P < .001) of the 12
      comparisons. Sexually abused boys showed a similar pattern on eight (P < .001)
      comparisons. CONCLUSIONS: Indications are that forced sex experiences are
      associated strongly with risky health behaviors in some adolescents, which should
      alert clinicians to the possibility of sexual abuse.

PMID- 8134212
TI  - Sex difference in disability and handicap at five years of age in children born
      at very short gestation.
AB  - OBJECTIVE: The objective of this study was to examine the relationship between
      sex and disabilities or handicaps at 5 years of age in infants born at less than
      32 weeks gestation. DESIGN: From the nationwide collaborative survey starting in
      1983, including perinatal data obtained during routine perinatal care and follow
      up assessments by the attending pediatricians, data from 1008 infants fulfilling
      the criteria were used. At age 5 years, a detailed assessment was performed by
      three specially trained pediatricians in 96% surviving infants (n = 648), of
      which 345 were boys. Each child was categorized as disabled or handicapped, using
      World Health Organization definitions. RESULTS: The prevalence of handicaps was
      three times greater in boys than in girls (21% vs 7%, odds ratio 3.2). Adjustment
      for gestational age and birth weight (logistic regression analysis) did not
      change this (odds ratio 3.5). Further adjustment by including perinatal variables
      such as idiopathic respiratory distress syndrome did not alter the odds ratios.
      The male excess in handicaps was not related to lower mortality, and therefore
      was not a mere consequence of a higher survival rate. The excess in handicaps was
      found in all assessed areas. CONCLUSIONS: Infants' sex seems to be an important
      determinant of handicaps. The perinatal variables used in the present study do
      not explain the difference in handicaps. These findings emphasize the need to
      include the sex distribution of a study population more systematically in
      analyses in future studies concerning long-term outcome of very preterm birth or
      low birth weight.

PMID- 8134213
TI  - Does a condom-promoting strategy (the Swiss STOP-AIDS campaign) modify sexual
      behavior among adolescents?
AB  - OBJECTIVE: To measure sexual behavior changes (especially the use of condoms)
      among adolescents after 5 years of a population-based acquired immunodeficiency
      syndrome prevention strategy at the national and regional level. DESIGN: Two
      comparative cross-sectional surveys by self-administered questionnaires were
      conducted in 1987 and 1990. SETTING: Two similar samples of 16- to 19-year-old
      apprentices. The two samples, 1987 (n = 1359) and 1990 (n = 817), are comparable
      in terms of sex, age, profession, and location. RESULTS: The percentage of boys
      who say they are sexually active has remained the same (75%) and has slightly
      increased among younger girls (65% to 75%, NS). The average number of partners
      has remained steady for boys and girls. Regular use of any contraceptive device
      has remained steady among girls (75%) and increased among boys (1987, 38%; 1990,
      54%; P < .001). In 1987 as well as in 1990, the condom was the most widely used
      method (> 90%), followed by the pill (50%), withdrawal (20%), and chemicals (5%).
      Rates were about the same for both sexes. Rates of irregular use of condoms
      increased among boys and girls (P < .01); regular use of condoms increased among
      boys (22% to 34%, P < .01) and girls (10% to 27%, P < .001); use of the pill has
      slightly decreased. CONCLUSIONS: During a 5-year period, the Swiss "STOP-AIDS"
      campaign and local interventions had had no real effect on the rate of sexual
      activity of apprentices but had had a positive effect on the use of contraception
      and condoms. The prevention strategy should (and will) be maintained in the
      future.

PMID- 8134214
TI  - Assessing the health status of children entering foster care.
AB  - OBJECTIVE: Most research on health problems of children in foster care has been
      cross-sectional, resulting in overselection of children who have been in care
      long-term and underrepresentation of children who are in care for a short time.
      METHODOLOGY: This paper reports on the health of a large cohort of children who
      had complete health examinations at the time of entry into foster care in a
      middle-size city during a 2-year period. RESULTS: Results indicate that > 90% of
      the children had an abnormality in at least one body system, 25% failed the
      vision screen, and 15% failed the hearing screen. The children were also lighter
      and shorter than the norm. Mental health screening revealed that 75% had a family
      history of mental illness or drug or alcohol abuse. Of children older than 3
      years of age, 15% admitted to or were suspect for suicidal ideation and 7% for
      homicidal ideation. Of the children younger than 5 years of age, 23% had abnormal
      or suspect results on developmental screening examinations. At the time of entry
      into foster care, 12% of the children required an antibiotic. More than half
      needed urgent or nonurgent referrals for medical services and, for children > 3
      years of age, more than half needed urgent or nonurgent referrals for dental and
      mental health services. Just 12% of the children required only routine follow-up
      care. CONCLUSIONS: The high prevalence and broad range of health needs of
      children at the time they enter foster care necessitate the design and
      implementation of better models of health care delivery for children in foster
      care.

PMID- 8134215
TI  - Providing comprehensive health care to children with chronic illness.
AB  - OBJECTIVES: To test whether a program of outreach and comprehensive health care
      for children with chronic disorders provides more complete care and reduces unmet
      health needs compared with traditional care. DESIGN: A pretest-posttest
      randomized control trial. SETTING: An inner-city municipal teaching hospital.
      SAMPLE: Two hundred nineteen systematically enrolled mothers of children with
      diverse chronic physical health conditions. INTERVENTIONS: A comprehensive
      outreach program, Pediatric Home Care (PHC), contrasted with Standard Care.
      MEASUREMENTS AND RESULTS: Nine elements of comprehensive care established in the
      literature as components of a basic package of care for those with chronic
      conditions. The PHC intervention addressed gaps in services and improved both the
      acquisition and maintenance of elements of comprehensive care. CONCLUSIONS: These
      data suggest mechanisms through which comprehensive care programs may contribute
      to the improvement in psychological and social outcomes previously reported for
      those in the PHC intervention.

PMID- 8134216
TI  - Pediatric clerkship performance in diverse community clinical settings.
AB  - OBJECTIVE: To determine whether multiple and diverse clinical settings and
      resources in a pediatric clerkship result in satisfactory performance by medical
      students and affect their choice of a pediatric residency after graduation.
      DESIGN: Retrospective study 1985 through 1990. SETTING: Medical students in a
      pediatric clerkship in a medical school that is part of a land grant university
      where the clinical curriculum is conducted in six geographically distinct
      communities. MAIN OUTCOME MEASURE: (1) Three performance criteria including:
      multiple choice final examination score, clinical performance evaluations by
      preceptors, and formal evaluation of patient written records. (2) Students
      matching with a pediatric or combined internal medicine/pediatric residency.
      RESULTS: Of 499 students 92.8% successfully passed all three criteria with no
      statistically significant differences between communities. A smaller percentage
      of students (15.2%) (community range, 6 to 18.5%) entered straight or combined
      pediatric residencies, whether or not a pediatric residency was present in the
      community. CONCLUSIONS: Medical students can achieve satisfactory competency in
      pediatric clerkships offered in diverse clinical settings, and choose pediatric
      residency training whether or not they are exposed to a pediatric residency
      during their clerkship. A problem-based learning curriculum does not hinder
      selecting pediatrics as a career choice.

PMID- 8134217
TI  - Altered blood pressure reactivity in adolescent diabetics.
AB  - OBJECTIVE: We examined hemodynamic responses to a variety of physiologic stimuli
      in 14 normotensive adolescents with type I diabetes and 45 healthy controls to
      determine whether structural vascular changes contribute to a reduced vasodilator
      capacity in adolescent diabetics. We asked, in adolescents with type I diabetes:
      (1) Are structural vascular changes present? (2) Are changes in the systemic
      vascular bed reflected in abnormal blood pressure regulation? and (3) Is abnormal
      vascular reactivity associated with either diabetes duration or control?
      METHODOLOGY: Diabetic subjects were outpatients treated at the Medical College of
      Virginia, ages 13 to 18 years. Diabetes duration averaged 7.5 years. Each subject
      underwent an echocardiogram, dynamic and isometric exercise testing, and forearm
      plethysmography. RESULTS: Compared to controls, diabetic subjects had (1) higher
      systolic and diastolic blood pressure during dynamic and handgrip exercise, (2)
      decreased forearm vasodilator capacity in response to ischemia, and (3) an
      increased aortic peak velocity. Group diastolic filling abnormalities were found,
      but these did not persist after adjustment for heart rate. The following
      variables were related to both diabetes duration and control (average
      glycosylated hemoglobin): (1) diastolic blood pressure during dynamic exercise,
      (2) resting forearm vascular resistance, and (3) forearm vascular reactivity. In
      addition, diabetes duration correlated with isometric exercise diastolic blood
      pressure, and diabetes control correlated with resting diastolic blood pressure.
      CONCLUSION: In young diabetics we found that (1) abnormalities of the resistance
      vessels of the forearm may be present, (2) the degree of vascular change is
      related to diabetes duration and control, and (3) aortic distensibility may be
      impaired.

PMID- 8134218
TI  - Lumbar cerebrospinal fluid opening pressure measured in a flexed lateral
      decubitus position in children.
AB  - OBJECTIVE: Lumbar punctures in children are generally performed in a flexed
      position. Published normal ranges for cerebrospinal fluid (CSF) opening pressure
      require measurement in an extended position, and flexion is known to increase
      lumbar CSF pressure. This study sought to determine a normal range (mean +/- 2
      SD) for lumbar CSF opening pressure measured in a flexed lateral decubitus
      position in children. METHODS: Opening pressure was measured in 33 children
      receiving diagnostic lumbar punctures or prophylactic intrathecal chemotherapy.
      Measurements were performed in a flexed lateral decubitus position. Patients with
      medical conditions affecting CSF pressure were excluded. RESULTS: Opening
      pressure (mean +/- SD) was 19.0 +/- 4.4 cm H2O. Opening pressure was not
      significantly affected by patient age or sex. Intrathecal chemotherapy and
      sedation also did not affect CSF pressure. CONCLUSIONS: The normal range for
      lumbar CSF opening pressure measured in a flexed lateral decubitus position in
      children is 10 to 28 cm H2O.

PMID- 8134219
TI  - Alteration in the proportion of CD4 T lymphocytes in a subgroup of human
      immunodeficiency virus-exposed-uninfected children.
AB  - OBJECTIVE: The age-related changes in the proportion of CD4 and CD8 lymphocytes
      in human immunodeficiency virus (HIV)-seronegative children born to HIV-infected
      mothers (seroreverters) were compared with the changes in these lymphocyte
      subsets in children born to seronegative women to assess a possible effect of
      exposure to HIV without infection. DESIGN: There were 146 seroreverter and 72
      seronegative children. The median CD4 and CD8 percentages for each of these two
      groups of children were compared retrospectively at 3-month intervals from birth
      through 27 months and at a tenth interval for the time beyond 27 months. The
      weighted average of the within-subject rate of change of CD4 and CD8 percentages
      were also compared between the two groups. Finally, for each subject, the
      proportion of the subject's CD4 percentage assays which were <10th percentile of
      the entire study population (30%) was calculated, and the distributions of the
      subject-specific proportions were then compared between the seronegative and
      seroreverter groups using the Wilcoxon rank sum test. The proportion of CD8
      assays <10th percentile (12%) or > 90th percentile (26%) were also computed for
      each subject, and the distributions of the proportions were compared similarly. .
      RESULTS: The median CD4 percentage of seroreverter children was lower than that
      for the seronegative children at every interval from birth through 27 months and
      for the last interval for values obtained at greater than 27 months, although the
      comparison was statistically significant only at the 4- to 6-month period. The
      weighted average of the within-subject rate of change of CD4 percentage was -0.09
      and -3.0 per year (P = .04), and of CD8 percentage was 1.3 and 1.0 (P = .67), for
      the seroreverter and seronegative children, respectively. There were
      significantly more children in the seroreverter group than in the seronegative
      group who had repeated assays in which the CD4 percentage was < 10th percentile
      for age (P < .00005). In addition, there was a subset of 10 seroreverter children
      (6.8%) who had CD4 percentages < 30% on > 50% of their assays, as compared with
      only one (1.4%) seronegative child. The proportion of CD8 assays < 10th
      percentile or > 90th percentile were not significantly different between the two
      groups of children. CONCLUSIONS: The CD4 proportions were persistently lower in
      the seroreverter than in the seronegative population, although only reaching
      statistical significance in 1 of 10 3-month intervals. This finding may be due to
      a subgroup of seroreverter children who have persistently low CD4 lymphocyte
      percentages.

PMID- 8134220
TI  - Selective intrapartum prophylaxis for group B streptococcus colonization:
      management and outcome of newborns.
AB  - OBJECTIVE: Intrapartum antibiotic prophylaxis (IAP) in mothers with group B
      streptococcus (GBS) colonization presents difficult neonatal management
      decisions. IAP was instituted in response to an increased incidence of early
      onset GBS sepsis (EOGBSS), and a study was conducted to evaluate the outcome of
      these newborns. METHODS: A study was undertaken at Truman Medical Center-East, a
      county hospital with a level 1 nursery. During the 20-month study period,
      prenatal GBS cultures were obtained on all mothers in their third trimester of
      pregnancy. At time of delivery, GBS-positive women who had at least one risk
      factor were to receive IAP. Risk factors included fever and/or amnionitis,
      premature labor, and prolonged rupture of membranes defined as > 6 hours.
      Screening laboratory tests were performed on all newborns whose mothers received
      IAP. Only the newborns with positive screening laboratory tests or symptoms of
      sepsis received further laboratory evaluation and antibiotic treatment. RESULTS:
      During the study, 2040 mothers gave birth to 2054 newborns. Three hundred thirty
      two mothers (16.3%) were colonized with GBS and 122 (37.0%) had at least one risk
      factor. IAP was given to 70 GBS-positive mothers. Thirty-three (27%) GBS-positive
      mothers with risk factors did not receive IAP for logistical reasons. Eleven full
      term newborns had EOGBSS: For case newborns, the mean duration of ruptured
      membranes was 13.7 hours (range 2.5 to 28 hours). Vertical transmission occurred
      as follows: Cutaneous colonization was found in 33 (12.5%) newborns born to 261
      mothers who received no IAP, and symptomatic EOGBSS was diagnosed in 9 (3.4%).
      Mothers who received one dose (n = 43) had three (6.9%) newborns with GBS
      colonization and two (4.7%) asymptomatic newborns with EOGBSS: No newborns born
      to 28 mothers who received two doses IAP had GBS colonization or were ill.
      Cutaneous vertical transmission was reduced (P = .03). Newborns born to GBS
      positive mothers with one or more risk factors who received IAP had significantly
      less EOGBSS (P < .05) than those who did not receive IAP. CONCLUSIONS: Selective
      IAP was administered safely to 21% of GBS-positive women, or 3.5% of all
      deliveries. IAP prevented EOGBSS when it could be given to GBS-positive mothers
      with a risk factor. Accurate identification of mothers with GBS colonization and
      their risk factors is essential for effective use of IAP. Earlier institution of
      IAP after rupture of membranes may reduce the risk of EOGBSS and the need for
      extensive infant evaluation.

PMID- 8134221
TI  - Province-based study of neurologic disability among survivors weighing 500
      through 1249 grams at birth.
AB  - BACKGROUND: As the mortality of children weighing 500 through 1249 g at birth
      decreases, the published rates of neurologic disability among survivors have
      caused concern. Outcome information from a province-based study in which
      perinatal/neonatal regional care is well developed and includes high-risk
      identification, early referral, organized transport, and outreach education,
      provides data from a Canadian source for comparison with epidemiologic reports.
      METHODS: Neurologic disability rates among 2- to 3-year-old survivors weighing
      500 through 1249 g at birth is provided based on all live births/neonatal
      survivors/1-year survivors born in Alberta, Canada to Alberta residents in 1990.
      RESULTS: Corrected survival to 1-year was 163 of 229 or 71% of live births of the
      total group weighing 500 through 1249 g. Of 168 live births, 143 or 85% weighing
      750 through 1249 g, free from lethal anomalies, survived. Based on 1-year
      survival, disability rates were: cerebral palsy, 67/1000; vision loss (acuity in
      the best seeing eye after correction, < 20/60), 12/1000; neurosensory hearing
      loss (loss of > or = 30 dB binaurally), 12/1000; and trainable/profound mental
      retardation, 18/1000. No survivor had a convulsive disorder. No vision loss or
      mental retardation as defined by this study occurred in survivors of > or = 750
      g. All children with cerebral palsy were or were projected to become ambulatory.
      CONCLUSIONS: Neurologic disability among small preterm surviving infants can
      occur less frequently than suggested by published reports. We believe this
      provincial study supports the value of well developed regional perinatal
      programs.

PMID- 8134222
TI  - Acetaminophen analgesia in neonatal circumcision: the effect on pain.
AB  - OBJECTIVE: Recognizing the concerns about the use of local anesthesia in neonatal
      circumcision, a painful procedure usually performed without analgesia or
      anesthesia, we undertook a study of acetaminophen for pain management of this
      procedure. DESIGN: A prospective, randomized, double-blind, placebo-controlled,
      clinical trial of acetaminophen analgesia in 44 healthy full-term neonates
      undergoing circumcision was conducted. Beginning 2 hours before Gomco
      circumcision, neonates received either acetaminophen (15 mg/kg per dose, 0.15
      mL/kg per dose) or placebo (0.15 mL/kg per dose) every 6 hours for 24 hours.
      Neonates were monitored intraoperatively for changes in heart rate, respiratory
      rate, and crying time. Postoperative pain was assessed at 30, 60, 90, 120, 360
      minutes, and 24 hours using a standardized postoperative comfort scoring system.
      Feeding behavior was also assessed before and after circumcision by nursing
      observation. RESULTS: Neonates in both groups showed significant increases in
      heart rate, respiratory rate, and crying during circumcision with no clinically
      significant differences observed between the groups. Postoperative comfort scores
      showed no significant differences between the groups until the 360-minute
      postoperative assessment, at which time the acetaminophen group had significantly
      improved scores (P < .05). Feeding behavior deteriorated in breast- and bottle
      fed neonates in both groups, and acetaminophen did not seem to influence this
      deterioration. CONCLUSIONS: This study confirms that circumcision of the newborn
      causes severe and persistent pain. Acetaminophen was not found to ameliorate
      either the intraoperative or the immediate postoperative pain of circumcision,
      although it seems that it may provide some benefit after the immediate
      postoperative period.

PMID- 8134223
TI  - Carbamate poisoning and oxime treatment in children: a clinical and laboratory
      study.
AB  - OBJECTIVE: (1) Retrospective evaluation of the clinical course of carbamate
      poisoning and the effect of oxime therapy in children. (2) In vitro study of the
      effect of oximes on the reactivation of carbamylated cholinesterase. DESIGN: (1)
      Clinical survey: The records of 26 children intoxicated with carbamates were
      examined retrospectively. The poisoning agents in all cases were positively
      identified as methomyl or aldicarb by gas chromatography-mass spectrometry. (2)
      Laboratory study: The direct effect of obidoxime and of pralidoxime on
      acetylcholinesterase activity in vitro was investigated in normal human packed
      red blood cells pretreated with an organophosphate (paraoxon) or a carbamate
      (aldicarb or methomyl). CLINICAL SETTING: Pediatric intensive care unit of a
      teaching hospital. PATIENTS: Twenty-six infants and young children (aged 1 to 8
      years) admitted to the pediatric intensive care unit with severe carbamate
      intoxication. INTERVENTIONS: All cases had been treated with repeated doses of
      atropine sulfate (0.05 mg/kg) administered every 5 to 10 minutes until muscarinic
      symptoms disappeared. Obidoxime chloride (Toxogonin, 6 mg/kg) was administered on
      admission, and again after 4 to 5 hours. RESULTS: Predominant symptoms were
      related to central nervous system and nicotinic effects. All the patients showed
      marked improvement within several hours and recovered completely within 24 hours.
      None of the children deteriorated and none showed exacerbation of cholinergic
      symptoms after obidoxime treatment. In vitro, oximes reactivated
      acetylcholinesterase inhibited with paraoxon, whereas no significant effect of
      oximes on carbamylated enzyme activity was observed. CONCLUSIONS: Based on the
      recovery of all cases, as compared with other reports of carbamate poisoning
      treated with atropine alone, it is concluded that, in the case of aldicarb or
      methomyl poisoning, oxime therapy apparently does not contribute to the recovery
      of poisoned patients. In cases of poisoning by an unknown pesticide or of mixed
      poisoning, oxime therapy can prove beneficial because no negative effects of the
      therapy can be discerned.

PMID- 8134224
TI  - Comparison of a three-component acellular pertussis vaccine with a whole-cell
      pertussis vaccine in 15- through 20-month-old infants.
AB  - OBJECTIVE: To compare the immunogenicity and reactogenicity of a diphtheria and
      tetanus toxoids and three-component acellular pertussis vaccine (DTaP) with a
      diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) when
      administered as a booster dose to infants 15 through 20 months of age. DESIGN:
      Randomized, double-blind, comparative study. SETTING: Three pediatric practices
      (two private; one hospital-based). PARTICIPANTS: One hundred and sixty-five
      healthy 15- through 20-month old infants. SELECTION PROCEDURES AND INTERVENTIONS:
      Infants were randomly assigned in a 2:1 ratio to receive vaccine from a single
      lot of DTaP or from commercially available DTwP. DTaP contained 25 micrograms of
      pertussis toxoid, 25 micrograms of filamentous hemagglutinin, 8 micrograms of
      pertactin (69-kilodalton outer membrane protein), 25 flocculating units of
      diphtheria toxoid, and 10 flocculating units of tetanus toxoid per 0.5-mL dose.
      DTwP contained one half the concentrations of diphtheria and tetanus toxoids
      compared with DTaP and a pertussis component with a potency of 4 U/0.5-mL dose.
      Serum samples were obtained on the day of immunization and 4 weeks later. Adverse
      reactions were recorded by parents for 7 days after immunization. An interval
      history was obtained 4 weeks after immunization. MEASUREMENTS AND RESULTS: IgG
      antibody to pertussis toxoid, filamentous hemagglutinin, pertactin, diphtheria
      toxoid, and tetanus toxoid was measured by an indirect enzyme-linked
      immunosorbent assay (ELISA) method. One month after immunization, the geometric
      mean antibody levels after DTaP compared with DTwP were: pertussis toxoid, 70.6
      vs 28 ELISA U/mL (P = .003); filamentous hemagglutinin, 183.4 vs 43 ELISA U/mL (P
      < .001); pertactin, 216 vs 49.9 ELISA U/mL (P < .001); diphtheria, 14.1 vs 14.9
      IU/mL (P = .74); and tetanus, 11.9 vs 14.8 IU/mL (P = .089). After immunization
      with DTaP, most local and systemic adverse experiences were significantly fewer
      compared with DTwP (P < .05). CONCLUSIONS: This three-component DTaP vaccine
      demonstrates significantly greater immune responses to pertussis toxoid,
      filamentous hemagglutinin, and pertactin, equivalent immune responses to
      diphtheria and tetanus toxoids, and significantly less reactogenicity compared
      with a licensed DTwP.

PMID- 8134225
TI  - Evaluation of recurrent pediatric syncope: role of tilt table testing.
AB  - OBJECTIVE: To determine the current practice and effectiveness of evaluating
      recurrent syncope in pediatric patients, and to establish the role of tilt table
      testing in the evaluation. DESIGN: Retrospective analysis of 54 pediatric
      patients with the history of syncope referred to cardiologists. Group I consisted
      of 27 patients examined without tilt table testing; group II consisted of 27
      patients whose examination included tilt table testing. RESULTS: Group I had an
      average of 5.4 studies and group II, 6.6 studies performed per patient. Studies
      included chest radiograph (16 vs 13), electrocardiogram (24 vs 27),
      echocardiography (21 vs 27), 24-hour electrocardiogram (14 vs 16),
      transtelephonic monitor (7 vs 8), electrophysiology study (1 vs 3), complete
      blood cell counts (11 vs 12), chemistries (10 vs 11), thyroid function test (3 vs
      3), neurology consult (12 vs 6), electroencephalogram (12 vs 5), and head
      computed tomographic scan (5 vs 3). Of the 298 non-tilt studies, the results of
      only 5 (1.6%) were abnormal. Diagnoses were made in 5 (18.5%) of 27 group I
      patients (Wolff-Parkinson-White syndrome, 1; conversion reaction, 2;
      hyperventilation, 1; migraines, 1), whereas diagnosis was made in 27 (100%) of 27
      group II patients (neurocardiogenic syncope, 25; conversion reaction, 2).
      CONCLUSION: An extensive workup is not routinely indicated in syncopal patients
      with a history consistent with neurocardiogenic syncope. Tilt table testing
      performed early in the evaluation will increase the probability of a diagnosis,
      and will often prevent the need for further extensive, expensive anxiety
      producing tests.

PMID- 8134226
TI  - National trends in Haemophilus influenzae meningitis mortality and
      hospitalization among children, 1980 through 1991.
AB  - OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccines were licensed
      for routine use in the United States in December 1987. We compared national
      trends in deaths and hospitalization from H influenzae meningitis among children
      < 5 years old before and after Hib conjugate vaccine licensure. METHODS: H
      influenzae meningitis mortality rates were calculated using data from the 1980
      through 1991 computerized national mortality files. Hospitalization rates from H
      influenzae meningitis were calculated using data from the 1980 through 1991
      National Hospital Discharge Surveys. Trends in H influenzae mortality and
      hospitalization from 1980 through 1887 were compared with trends from 1988
      through 1991. Trends for Streptococcus pneumoniae and Neisseria meningitidis
      meningitis were also examined. RESULTS: From 1980 through 1987, mortality from H
      influenzae meningitis decreased an average of 8.5% each year, compared with a 48%
      annual decrease from 1988 through 1991 (P < .001 for difference in trends). H
      influenzae meningitis hospitalization rates increased 1% each year from 1980
      through 1987, and decreased an average of 34% each year from 1988 through 1991.
      There was no significant difference in mortality or hospitalization trends for S
      pneumoniae or N meningitidis meningitis during the two periods. Among infants, H
      influenzae meningitis mortality decreased an average of 8% per year from 1980
      through 1987 and 43% per year from 1988 through 1991. One- to four-year-old
      children had similar average annual declines, 8% and 58% for the two periods.
      Although there were regional differences in the absolute mortality rates, all
      regions of the country had similar trends in meningitis mortality. CONCLUSIONS:
      Among US children < 5 years old, we found substantial decreases in deaths and
      hospitalization from H influenzae meningitis, but not S pneumoniae or N
      meningitidis meningitis, in the years after Hib conjugate vaccine licensure.
      These results suggest that the declines in H influenzae meningitis were due
      primarily to the use of Hib conjugate vaccines.

PMID- 8134227
TI  - Physical activity, fitness, and health in children: a close look.

PMID- 8134228
TI  - Ribavirin. Red Book Committee recommendations questioned.

PMID- 8134229
TI  - Brain injury caused by intraventricular hemorrhage: is indomethacin the silver
      bullet for prevention?

PMID- 8134230
TI  - Prevention of periventricular hemorrhage.

PMID- 8134231
TI  - The practice of pediatrics in the era of vaccines effective against Haemophilus
      influenzae type b.

PMID- 8134232
TI  - Recommended timing of routine measles immunization for children who have recently
      received immune globulin preparations. American Academy of Pediatrics Committee
      on Infectious Diseases.

PMID- 8134233
TI  - Assessing physical activity and fitness in the office setting. American Academy
      of Pediatrics Committee on Sports Medicine and Fitness.

PMID- 8134234
TI  - Risk of injury from baseball and softball in children 5 to 14 years of age.
      American Academy of Pediatrics Committee on Sports Medicine.

PMID- 8134235
TI  - A unique complication of nonsteroidal anti-inflammatory drug use.

PMID- 8134236
TI  - Sepsis + C-reactive protein.

PMID- 8134237
TI  - Asthma treatment in the emergency department.

PMID- 8134238
TI  - Freezing with chicken juice.

PMID- 8134239
TI  - Objections to AAP statement on homosexuality and adolescence.

PMID- 8134240
TI  - Perceptual dimensions of tactile surface texture: a multidimensional scaling
      analysis.
AB  - The purpose of this study was to examine the subjective dimensionality of tactile
      surface texture perception. Seventeen tactile stimuli, such as wood, sandpaper,
      and velvet, were moved across the index finger of the subject, who sorted them
      into categories on the basis of perceived similarity. Multidimensional scaling
      (MDS) techniques were then used to position the stimuli in a perceptual space on
      the basis of combined data of 20 subjects. A three-dimensional space was judged
      to give a satisfactory representation of the data. Subjects' ratings of each
      stimulus on five scales representing putative dimensions of perceived surface
      texture were then fitted by regression analysis into the MDS space. Roughness
      smoothness and hardness-softness were found to be robust and orthogonal
      dimensions; the third dimension did not correspond closely with any of the rating
      scales used, but post hoc inspection of the data suggested that it may reflect
      the compressional elasticity ("springiness") of the surface.

PMID- 8134241
TI  - Occlusion cues contribute to orientation judgments of occlusion-defined contours.
AB  - Occlusion cues defining a contour in a 2-D stimulus pattern were shown to
      contribute to the accuracy of orientation judgments of that contour. The stimulus
      pattern was altered so that the occlusion cues became ambiguous, by introducing a
      textured background suggesting transparency of the stimulus pattern. Orientation
      judgments then became significantly less accurate. This finding shows that
      occlusion cues in 2-D patterns can be behaviorally relevant, in addition to
      generating the subjective percept commonly known as an illusory contour. The
      disruptive effect of the textured background on orientation judgments remained
      when no texture elements were present in the vicinity of the contour. This
      suggests that the generation of occlusion-defined contours relies as much on an
      evaluation of the surfaces at either side of the contour as being opaque as it
      does on local encoding of occlusion cues close to the contour. Finally,
      orientation sensitivity measured with contours defined by other than occlusion
      cues was not altered after the introduction of a textured background.

PMID- 8134242
TI  - Efficiency of visual selection in duplex and conjunction conditions in partial
      report.
AB  - Factors that determine the efficiency of visual selection were investigated in
      two precued partial-report experiments. There were four selection conditions: a
      color condition (e.g., selecting purple letters among blue letters), a class
      condition (e.g., selecting letters among digits), a duplex condition (e.g.,
      selecting purple letters among blue digits; that is, the targets differed from
      the distractors both in color and in alphanumeric class), and a conjunction
      condition (e.g., selecting purple letters among blue letters and purple digits;
      that is, the targets differed from the distractors either in color or in
      alphanumeric class). The efficiency of visual selection was highest in the duplex
      condition and lowest in the conjunction condition. The difference in performance
      across the different selection conditions within subjects was accounted for by
      variation in the value of a single parameter of the fixed-capacity independent
      race model (FIRM) proposed by Shibuya and Bundesen (1988), which assumes
      independent parallel processing, limitations in both processing capacity and
      storage capacity, and time-invariant selectivity. By assuming that the factors
      that determine the efficiency of selection in the color and class conditions also
      underlie the efficiency of selection in the duplex and conjunction conditions, an
      extension of FIRM, FIRM+, accounted for the relationship with respect to
      efficiency of selection among the different conditions.

PMID- 8134244
TI  - Perception of sweetness and bitterness in different vehicles.
AB  - In the present study, we investigated taste-taste, taste-vehicle, and
      simultaneous taste-vehicle-taste mixtures. Subjects made estimates of the
      sweetness and bitterness of 27 stimuli. Sucrose (292, 585, and 1170 mM), caffeine
      (13, 26, and 52 mM), and binary mixtures of low (292-13 mM), middle (585-26 mM),
      and high (1170-52 mM) levels of both components were dispersed in water,
      carboxymethylcellulose (CMC) 1% w/v, and gelatin 6% w/v. The sweetness and
      bitterness of the sucrose-vehicle-caffeine combinations were significantly weaker
      than the respective sucrose-vehicle and caffeine-vehicle combinations. The
      emerged mutual suppressive effects were asymmetrical and persisted when both
      tastants were presented in CMC and gelatin. Moreover, the increase in vehicle
      consistency and the simultaneous addition of another taste reduced the perceived
      intensity of a taste either presented alone or dissolved in water. For both
      sweetness and bitterness, the total taste suppression observed was always
      significant.

PMID- 8134243
TI  - Detection of changes in speed and direction of motion: reaction time analysis.
AB  - Observers reacted to the change in the movement of a random-dot field whose
      initial velocity, V0, was constant for a random period and then switched abruptly
      to another value, V1. The two movements, both horizontally oriented, were either
      in the same direction (speed increments or decrements), or in the opposite
      direction but equal in speed (direction reversals). One of the two velocities, V0
      or V1, could be zero (motion onset and offset, respectively). In the range of
      speeds used, 0-16 deg/sec (dps), the mean reaction time (MRT) for a given value
      of V0 depended on magnitude of V1-V0 only: MRT approximately r+c(V0)/magnitude of
      V1-V0 beta, where beta = 2/3, r is a velocity-independent component of MRT, and
      c(V0) is a parameter whose value is constant for low values of V0 (0-4 dps), and
      increases beginning with some value of V0 between 4 and 8 dps. These and other
      data reviewed in the paper are accounted for by a model in which the time
      position function of a moving target is encoded by mass activation of a network
      of Reichardt-type encoders. Motion-onset detection (V0 = 0) is achieved by
      weighted temporal summation of the outputs of this network, the weights assigned
      to activated encoders being proportional to their squared spatial spans. By means
      of a "subtractive normalization," the visual system effectively reduces the
      detection of velocity changes (a change from V0 to V1) to the detection of motion
      onset (a change from 0 to V1-V0). Subtractive normalization operates by
      readjustment of weights: the weights of all encoders are amplified or attenuated
      depending on their spatial spans, temporal spans, and the initial velocity V0.
      Assignment of weights and weighted temporal summation are thought of as special
      purpose computations performed on the dynamic array of activations in the motion
      encoding network, without affecting the activations themselves.

PMID- 8134245
TI  - Masking disrupts recovery of location information.
AB  - In two experiments, we tested subjects' ability to localize a letter in a
      character string with identification controlled by varying the delay of a mask,
      dimming the display, or deleting some of the dots used to define the letters on
      the cathode-ray screen. The first experiment involved two tasks. In the first
      task, subjects indicated whether or not a letter named verbally had been present
      in an eight-letter target string. In the second task, they localized a letter
      named verbally in the target string; the target string was presented by using
      display parameters shown in the first task to hold character identification
      between 70% and 75% correct. In the second experiment, we tallied errors in a
      partial-report bar-probe study after equating performance across the
      manipulations of display quality. Masking disrupted subjects' ability to recover
      location information more than either a manipulation of stimulus luminance or a
      manipulation of its visual form.

PMID- 8134246
TI  - Angular subtense effects on perception of polar and parallel projections of
      cubes.
AB  - Many authors contend that the perception of 2-D drawings of a 3-D object is
      governed by polar projective geometry. A problem for this position is that
      observers accept parallel projections, which are not produced with polar
      projective geometry, as accurate representations of 3-D objects. In Experiments 1
      and 2, we used two different standards of comparison to study the perceptions of
      three line drawings of cubes--correct polar projections of cubes with subtenses
      of 15 degrees and 35 degrees, and a parallel projection--at five different
      angular subtenses. In Experiment 1, 14 observers judged each drawing when it
      subtended about 35 degrees, 15 degrees, 5 degrees, 4 degrees, and 2 degrees in
      width. Subjects used an 8-point rating scale to compare each drawing with a
      correct polar projection of a cube subtending 35 degrees, viewed with the drawing
      subtending 15 degrees. As predicted, both polar projections had their highest
      ratings at their correct vantage points. Ratings for the parallel projection were
      highest at small angular subtenses and decreased when it subtended 35 degrees.
      These findings were supported by a second experiment in which the 15 degrees
      polar projection was set at a 5 degrees viewing angle as a standard. In
      Experiment 3, 15 observers compared the three drawings, viewed at a second set of
      angular subtenses (30 degrees, 35 degrees, 40 degrees, 45 degrees, and 50
      degrees), with a standard, the 35 degrees polar set at 45 degrees. Ratings fell
      with increases in viewing angle, and the parallel projection was rated lowest.
      The results indicate that parallel projections are assessed as polar projections
      that are correct for objects at a small angular subtense. Furthermore,
      projections at a small angular subtense are robust; that is, they are acceptable
      over a wide range of angular subtenses. We suggest that robustness can be
      explained by the modest variability in the proportions of pictures of cubes
      subtending small angles.

PMID- 8134247
TI  - The role of spatial frequency in the processing of hierarchically organized
      stimuli.
AB  - Can spatial frequency differences between local and global forms account for
      differences in the way different levels of structure are analyzed? We examined
      this question by having subjects identify local or global forms of hierarchical
      stimuli that had been contrast balanced. Contrast balancing eliminates low
      spatial frequencies, so that both local and global forms must be identified on
      the basis of high spatial frequency information. Response times (RTs) to global
      (but not local) forms were slowed for contrast-balanced stimuli, suggesting that
      low spatial frequencies mediate the global RT advantage typically found. In
      contrast, interference between local and global forms was little affected by
      contrast balancing or by shifts of attention between local and global forms,
      suggesting that it does not result from inhibitory interactions between spatial
      frequency channels or from temporal precedence of low versus high spatial
      frequency information. Finally, shifts of attention between local and global
      forms were also little affected by contrast balancing, suggesting that they were
      not based on spatial frequency.

PMID- 8134248
TI  - Hemispheric differences in the interference among components of compound
      gratings.
AB  - The relationship between local/global and high/low spatial-frequency processing
      in hemispheric asymmetries was explored. Subjects were required to judge the
      orientation of a high- or low-spatial-frequency component of a compound grating
      presented in the left visual field (LVF) or right visual field (RVF). In
      Experiment 1, attention was focused on one or the other component. A signal
      detection analysis indicated that sensitivity (d') to the high-spatial-frequency
      target was reduced more by the presence of the low-spatial-frequency component
      when both were presented in the LVF rather than in the RVF. In Experiment 2,
      subjects determined whether a target orientation was present, independent of
      spatial frequency at only a single level (i.e., at the high- or low-spatial
      frequency level), as opposed to both or neither level. An RVF/LH (left
      hemisphere) advantage was found when the decision was based on the orientation of
      the high-frequency component. The asymmetrical influence of visual field of
      presentation and spatial frequency upon sensitivity is discussed in terms of
      hemispheric differences in the magnitude of inhibition between spatial-frequency
      channels and in the role of transient channel activity to capture and direct
      higher order attentional processes.

PMID- 8134249
TI  - Harmonic accents in inference of metrical structure and perception of rhythm
      patterns.
AB  - Research on rhythmic structure is somewhat fragmented, due in part to
      differential use of terminology and a lack of research on the timing of harmonic
      accents. In this study, a harmonic and a temporal accent were pitted against each
      other in such a way as to form different rhythm patterns. In addition, two
      harmonic conditions that varied in the frequency of chord presentations (i.e.,
      the composite rhythm) but not in the frequency of chord changes (i.e., the
      harmonic rhythm) were presented. Musicians and nonmusicians were requested to
      report perceived rhythm patterns in an attempt to determine the relative salience
      of the harmonic and temporal accents. In addition, a behavioral measure of the
      perceived meter was taken. Results indicated that the location of chord changes
      was the main determinant of subjects' rhythmic perceptions and the perceived
      onset of a measure. Furthermore, although subjects primarily inferred different
      meters based on the composite rhythm, an interaction of metrical and rhythmic
      choices was found, indicating that perception of rhythm patterns and inference of
      metrical structure may not always be independent.

PMID- 8134250
TI  - Effects of capacity demands on picture viewing.
AB  - Effects of cognitive-resource demands on picture-viewing patterns were
      investigated. The eye fixations of 72 subjects were recorded as the subjects
      viewed pictures and concurrently performed one of three listening tasks. Half of
      the subjects were asked to remember certain objects from the pictures and half
      had no-memory instructions. Concurrent auditory monitoring increased
      interfixation distances and the frequency of fixations on regions of high
      informativeness, and decreased the area of the pictures explored and the memory
      for objects in the scenes. It is suggested that the demands on cognitive
      resources influenced subjects' ability to encode and integrate fixated
      information and therefore prolonged the normal first phase of viewing, described
      by Buswell (1935).

PMID- 8134251
TI  - Attention demands during reading and the occurrence of brief (express) fixations.
AB  - Eye movements were recorded while subjects read passages of text repeatedly
      (Experiment 1) and while normal text and strings of homogeneous letters were
      fixated (Experiment 2). Text repetition decreased fixation durations and
      increased saccade size, presumably because it decreased attention demands.
      Irrespective of repetition, however, no distinct distribution of brief (express)
      fixations emerged. In Experiment 2, fixation durations were shorter and saccades
      were larger when strings of homogeneous letters were "read," indicating that this
      condition decreased attention demands. Again, however, no distinct distribution
      of express fixations emerged. These findings pose problems for the view that
      attentional processes determine the occurrence of brief (express) fixation
      durations in reading. Supplementary analyses of Experiments 1 and 2 suggested
      that visuospatial processing affected fixation durations, irrespective of
      linguistic processing demands.

PMID- 8134252
TI  - Double luminal and vascular perfusion of chicken jejunum: studies on 3-O-methyl-D
      glucose absorption.
AB  - The aims of the present study were: (1) to set up a procedure for simultaneous
      vascular and luminal perfusion of the chicken jejunum; (2) to assess the
      transport capacity of the tissue under such conditions, and (3) to study the
      effects of phloretin and theophylline, given through the vascular perfusate, on 3
      O-methyl-D-glucose intestinal transport. The perfusion procedure described
      allowed the control of intestinal and vascular inflow rates and perfusion
      pressures so that these parameters could be adjusted to physiological values. A
      perfluorochemical emulsion was used as oxygen carrier for the vascular perfusate.
      The absorptive function of the perfused tissue was assessed by means of its
      ability to transport 3-O-methyl-D-glucose. Furthermore, ultrastructure
      preservation was evaluated by scanning and transmission electron microscopy.
      Results indicate that the perfused tissue kept its transport capacity and
      morphology intact throughout the 120-min experimental period. Moreover, no
      hypersecretion was observed as indicated by the constancy of perfusate volumes
      and perfusion pressures. Phloretin (1 mM) or theophylline (10 mM) added to the
      vascular perfusate markedly reduced the transfer of 3-O-methyl-D-glucose from the
      enterocyte to the vascular fluid without affecting the uptake from the lumen. Our
      results suggest that this preparation may be used as an alternative tool for the
      study of intestinal absorption processes in avian species, particularly when
      complete examination is required of the efflux of substrates from the intestinal
      lumen to the vascular fluid.

PMID- 8134253
TI  - Isolated perfused rabbit colon crypts: stimulation of Cl- secretion by forskolin.
AB  - The aim of this study was to characterize ion conductances and carrier mechanisms
      of isolated in vitro perfused rabbit colonic crypts. Crypts were isolated from
      rabbit colon mucosa and mounted on a pipette system which allowed controlled
      perfusion of the lumen. In non-stimulated conditions basolateral membrane voltage
      (Vbl) was -65 +/- 1 mV (n = 240). Bath Ba2+ (1 mmol/l) and verapamil (0.1 mmol/l)
      depolarized Vbl by 21 +/- 2 mV (n = 7) and 31 +/- 1 (n = 4), respectively.
      Lowering of bath Cl- concentration hyperpolarized Vbl from -69 +/- 3 to -75 +/- 3
      mV (n = 9). Lowering of luminal Cl- concentration did not change Vbl. Basolateral
      application of loop diuretics (furosemide, piretanide, bumetanide) had no
      influence on Vbl in non-stimulated crypts. Forskolin (10(-6) mol/l) in the bath
      depolarized Vbl by 29 +/- 2 mV (n = 54) and decreased luminal membrane
      resistance. In one-third of the experiments a spontaneous partial repolarization
      of Vbl was seen in the presence of forskolin. During forskolin-induced
      depolarization basolateral application of loop diuretics hyperpolarized Vbl
      significantly and concentration dependently with a potency sequence of bumetanide
      > piretanide > or = furosemide. Lowering bath Cl- concentration hyperpolarized
      Vbl. Lowering of luminal Cl- concentration from 120 to 32 mmol/l during forskolin
      induced depolarization led to a further depolarization of Vbl by 7 +/- 2 mV (n =
      10). We conclude that Vbl of rabbit colonic crypt cells is dominated by a K+
      conductance. Stimulation of the cells by forskolin opens a luminal Cl-
      conductance. Basolateral uptake of Cl- occurs via a basolateral Na+:2Cl-:K+
      cotransport system.

PMID- 8134254
TI  - [Arginine]vasopressin hydrolyses phosphoinositides in the medullary thick
      ascending limb of mouse nephron.
AB  - NaCl reabsorption across the thick ascending limb of Henle's loop (TAL) is
      stimulated by several hormones, in particular vasopressin acting through V2
      receptors and cyclic AMP production. This study used suspensions of medullary TAL
      (mTAL) tubules from the mouse nephron to investigate the possibility that,
      besides activating adenylyl cyclase, vasopressin also stimulates phospholipase C
      via V1 receptor occupancy. Two different methods, phosphoinositide labelling and
      inositol trisphosphate (InsP3) radioimmunoassay, were used to show that
      [arginine]vasopressin (AVP) rapidly stimulated the formation of InsP3, which
      peaked at 200%-250% of control within the first minute of incubation with 10
      nmol/l vasopressin at 37 degrees C, and declined to basal level after 5-10 min.
      Dose/response curves for InsP3, established at 30 degrees C and 37 degrees C
      using radioimmunoassay, showed a half-maximal stimulation of InsP3 production at
      about 1 nmol/l AVP and a maximal response at 10 nmol/l. Similar values were
      obtained for the response to AVP in terms of cAMP accumulation. InsP3 content in
      the presence of higher concentrations of AVP (1 mumol/l) was significantly lower
      (P < 0.001) than in the presence of 10 nmol/l AVP, giving a bell-shaped
      appearance to the dose/response curve at 37 degrees C but not at 30 degrees C.
      The V2 receptor agonist, 1-deamino-[8-D-Arg]vasopressin (dAVP) did not stimulate
      the formation of InsP3, and the V1 receptor antagonist d(CH2)5[Tyr(Me)2]AVP
      inhibited AVP-induced InsP3 formation, which therefore appeared to be mediated by
      V1 receptor occupancy. Under the same conditions, AVP also induced the formation
      of diradylglycerol via V1 receptor activation, with an analogous dose/response
      curve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134255
TI  - Long-term elevations of dietary sodium produce parallel increases in the renal
      excretion of urodilatin and sodium.
AB  - The effects of dietary sodium intake on the renal excretion of urodilatin and of
      sodium were examined in six healthy male subjects. The 24-day study period was
      divided into three phases of 8 days each. Subjects ingested 2.8 mequiv sodium (kg
      body weight)-1 day-1 during the first phase, 5.6 mequiv (kg body weight)-1 day-1
      during the second phase, and 8.4 mequiv (kg body weight)-1 day-1 during the third
      phase. The excretion of both sodium (P < 0.002) and urodilatin (P < 0.006)
      increased in response to the increasing dietary sodium, while urine flow did not
      change. Urinary urodilatin excretion correlated closely with renal sodium
      excretion (P < 0.001). Serum aldosterone levels (P < 0.01) as well as serum renin
      levels (P < 0.05) significantly decreased with increasing sodium intake. Plasma
      [Arg]vasopressin levels increased significantly (P < 0.05). Plasma atrial
      natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were
      unaltered by the changes in sodium intake. We conclude from these results that
      the renal natriuretic peptide, urodilatin, but not the main cardiac member of the
      natriuretic peptide family may be involved in the regulation of day-to-day sodium
      balance.

PMID- 8134256
TI  - Chloride transport in brush-border membrane vesicles from chick jejunum.
AB  - This study sought to characterize the mechanism(s) of Cl- transport across brush
      border membrane vesicles (BBMV) isolated from chick jejunum. An inwardly directed
      proton gradient stimulated chloride (36Cl-) uptake. This uptake was inhibited by
      SITS and H2-DIDS. pH-gradient-stimulated Cl- uptake was electroneutral, since it
      was only slightly decreased by voltage clamping the BBMV with K+ and valinomycin.
      An outwardly directed HCO3- gradient significantly increased chloride uptake in
      the presence of a pH gradient. pH-driven chloride uptake was reduced by the
      presence of several anions in the uptake buffer. The rank order of potency for
      inhibition of pH-driven Cl- uptake was Cl- > SCN- > HCO3- > I- > Glu- > HPO4(2-).
      In the absence of a pH gradient, chloride was less concentrated inside the
      vesicles than outside. Chloride uptake under these conditions was stimulated by a
      positive electrical potential inside the vesicles. This stimulation was inhibited
      by the addition of several anions outside the vesicles. The order of inhibitory
      potency was SCN- > I- > Cl- > HCO3- > Glu- > HPO4(2-). The results are consistent
      with the presence of a Cl-/base exchanger and a chloride conductance pathway in
      the brush-border membrane of chick small intestine.

PMID- 8134258
TI  - The Na(+)-HCO3- cotransporter operates with a coupling ratio of 2 HCO3- to 1 Na+
      in isolated rabbit renal proximal tubule.
AB  - All the relevant literature reports indicate that net rates of salt and water
      absorption and cell membrane potentials (Vb) are lower, but intracellular Na+
      concentration is higher in rabbit renal proximal tubule in vitro than in rat
      proximal tubule in vivo. Since the different driving forces should influence
      basolateral Na(+)-HCO3- cotransport we have studied the operation of the
      cotransporter in isolated rabbit renal proximal tubule in vitro with special
      emphasis on the stoichiometry of flux coupling (q). Using conventional and ion
      selective intracellular microelectrodes three series of experiments were
      performed: (a) we determined the Vb response to a 2:1 reduction of bath HCO3- or
      Na+ concentration, (b) we determined initial efflux rates of HCO3- or Na+ ions in
      response to a sudden 10:1 reduction of bath HCO3- concentration, and (c) we
      collapsed the tubules and determined electrochemical driving forces of Na+ and
      HCO3- across the basolateral cell membrane under conditions approaching zero net
      flux in the control state in the presence of Ba2+- and in Cl(-)-free solutions.
      All measurements concurrently yielded a coupling ratio of approximately two HCO3-
      ions to one Na+ ion (q = 2). This result contrasts with the ratio q = 3, which we
      have previously observed in similar experiments on rat renal proximal tubule in
      vivo [Yoshitomi et al. (1985) Pflugers Arch 405:360] and which was also observed
      on rabbit renal basolateral cell membrane vesicles in vitro [Soleimani et al.
      (1987) J Clin Invest 79:1276].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134257
TI  - Ochratoxin A impairs "postproximal" nephron function in vivo and blocks plasma
      membrane anion conductance in Madin-Darby canine kidney cells in vitro.
AB  - Ochratoxin A (OTA) is a widespread nephrotoxin which causes porcine nephropathy
      and is supposed to have caused the human Balkan endemic nephropathy. We performed
      experiments in vivo and in vitro to elucidate the mechanism of OTA action in
      renal epithelium. Application of OTA to male Wistar rats [1.25 mumol/(kg.day)]
      for 6 days led to a reduction of glomerular filtration rate (to 63% of control),
      an increased fractional water (194% of control), Na+ (199% of control), K+ (147%
      of control) and Cl- (270% of control) excretion and an increased dependence of
      the osmole clearance on urine flow. Acute application of OTA to rats (3 mumol/kg)
      increased urinary pH from 6.0 +/- 0.2 to 6.6 +/- 0.1 and urinary NaCl excretion,
      but decreased titratable acid excretion to 47% of control. As these in vivo
      findings may be the result of an action of OTA beyond the proximal tubule
      ("postproximal") we investigated the effect of OTA on cultured Madin-Darby canine
      kidney (MDCK) cells, regarded as a model of collecting duct epithelium. In
      confluent monolayers formed by MDCK cells OTA reduced the number of domes in a
      dose-dependent manner and impaired the formation of a transepithelial Cl-
      gradient. Electrophysiological measurements in giant MDCK cells revealed that OTA
      blocks fractional anion conductance of the plasma membrane with an IC50 value of
      30 +/- 5 nmol/l, unmasking OTA as a naturally occurring anion conductance blocker
      about 20-times more effective than the most potent synthetic blocker 5-nitro-2-(3
      phenylpropyl-amino) benzoic acid (NPPB) (IC50 = 600 +/- 50 nmol/l).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8134259
TI  - Cardiac sympathetic denervation does not change the load dependence of the left
      ventricular end-systolic pressure/volume relationship in dogs.
AB  - It has been shown that in the intact canine heart the left-ventricular end
      systolic pressure/volume relation (ESPVR) depends on loading conditions: an
      increase in arterial vascular resistance causes a leftwards shift and a steeper
      slope of the ESPVR, suggesting an increased inotropic state. Our purpose was to
      investigate the possible contribution of the sympathetic nervous system to this
      load sensitivity of the ESPVR, using intact, but denervated, hearts with normal
      coronary perfusion and afterload. We used two types of loading intervention:
      venous volume infusion and gradual occlusion of the descending aorta. ESPVRs were
      obtained in six anaesthetized open-chest dogs, both before and after bilateral
      ablation of the stellate ganglia. To exclude the influence of heart rate changes,
      bilateral vagotomy was performed and the heart was paced. The absence of
      (unpaced) heart rate changes in response to pressure alterations was used to
      confirm total denervation. Left ventricular pressure was measured with a
      micromanometer and volume with a conductance catheter. ESPVRs were essentially
      linear and characterized by their slope (Ees) and volume intercept at 12 kPa
      (V12). We found that Ees (P < 0.0001) and V12 (P < 0.05) were both significantly
      different during pressure and volume interventions (0.67 +/- 0.29 and 0.41 +/-
      0.18 kPa/ml for Ees and 16.2 +/- 8.2 and 18.2 +/- 8.4 ml for V12 respectively).
      Denervation did not significantly affect the parameters of the ESPVR obtained by
      either volume infusion or aortic occlusion. Two-way analysis of variance revealed
      no significant interactive effect between denervation and intervention,
      indicating that the sympathetic nervous system does not influence the load
      dependency of the ESPVR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134260
TI  - Primary sequence and functional expression of a novel beta subunit of the P
      ATPase gene family.
AB  - The cortical collecting tubule (CCT) of the mammalian kidney reabsorbs sodium and
      potassium, processes that are mediated by Na/K-ATPase and H/K-ATPase. CCT is also
      an important site for proton secretion, which is driven, in part, by H/K-ATPase.
      Na/K-ATPase and H/K-ATPase are members of the ion-motive P-ATPase gene family.
      They are closely related plasma membrane proteins which consist of alpha beta
      heterodimers. The urinary bladder of the toad Bufo marinus is the amphibian
      counterpart of mammalian CCT. We have previously characterized a ouabain
      resistant Na/K-ATPase [see ref. 17], from TBM cells, a clonal cell line derived
      from the toad bladder, which expresses transepithelial sodium transport. In the
      present study, we report the primary sequence and functional expression of a
      novel beta subunit (beta bladder = beta b1) isolated from a toad bladder
      epithelial cell cDNA library. The deduced polypeptide is 299 amino acids in
      length and has a predicted molecular mass of 33 kDa. The beta b1 protein exhibits
      35% amino acid identity to the previously characterized beta 1 of B. marinus Na/K
      ATPase and 39% identity with beta 3 of B. marinus Na/K-ATPase. It shares 38%
      identity with the mammalian beta gastric H/K-ATPase and 52% with the mammalian
      beta 2 Na/K-ATPase. Northern blot analysis shows that a 1.4 x 10(3)-base mRNA is
      expressed at a high level in bladder epithelial cells and eye and at a trace
      level in kidney; it is not detectable in significant amounts in the stomach,
      colon and small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134262
TI  - Effect of 2,3-butanedione monoxime on smooth-muscle contraction of guinea-pig
      portal vein.
AB  - Effects of 2,3-butanedione-2-monoxime (BDM) on the contraction of intact and
      skinned smooth muscles from guinea-pig portal vein were examined. In intact
      preparations loaded with fura-2, 5-10 mM BDM markedly suppressed Ca2+ transients
      and force developments induced by 154 mM potassium and by phenylephrine (0.1 mM).
      On the other hand, in Ca(2+)-free depolarizing solution, BDM did not suppress
      phenylephrine (0.1 mM)-induced Ca2+ transient and force development. In skinned
      preparations obtained with Staphylococcus aureus alpha-toxin treatment, BDM did
      not markedly affect active force development. The above results indicate that BDM
      suppresses contraction of the portal vein mainly by the inhibition of voltage
      dependent cytosolic Ca2+ transients. An additional result suggests that BDM
      suppresses the force-enhancing effect of alpha 1-adrenergic agents on the
      contractile elements.

PMID- 8134261
TI  - Sodium channel inactivation kinetics of rat sensory and motor nerve fibres and
      their modulation by glutathione.
AB  - Na+ channel currents of rat motor and sensory nerve fibres were studied with the
      patch-clamp technique on enzymatically demyelinated axons. Differences between
      motor and sensory fibres in multi-channel inactivation kinetics and the gating of
      late single-channel currents were investigated. In the axon-attached mode,
      inactivation of multi-channel Na+ currents in sensory axons was best fitted with
      a single time constant while for motor axons two time constants were needed. Late
      single-channel currents in sensory axons were characterized by short openings
      whereas motor axons exhibited additional long single-channel openings. In
      contrast, in excised, inside-out membrane patches, no differences between motor
      and sensory fibres were found; in both types of fibre inactivation of multi
      channel Na+ currents proceeded with two time constants and late single-channel
      currents showed short and long openings. After application of the reducing agent
      glutathione to the cytoplasmic side of excised inside-out patches, inactivation
      of Na+ currents in both motor and sensory fibres proceeded with a single, fast
      exponential time constant and late currents appeared with short openings only.
      These data indicate that the axonal metabolism may contribute to the different
      inactivation kinetics of Na+ current in motor and sensory nerve fibres.

PMID- 8134263
TI  - Adaptive modification of the cat's vestibulospinal reflex during sustained
      vestibular and neck stimulation.
AB  - In decerebrate cats, rotation about the longitudinal axis of the whole animal at
      0.15 Hz, +/- 10 degrees produced an increased electromyogram (EMG) activity of
      the triceps brachii during side-down tilt and a decreased activity during side-up
      tilt. This vestibulospinal reflex (VSR) was tested before, during and after a
      sustained (3-h) period of roll tilt of the head at the parameters indicated
      above, associated with a synchronous roll tilt of the body at 0.15 Hz, but at the
      peak amplitude of either 12.5 degrees or 7.5 degrees. This additional stimulus
      led to 2.5 degrees of neck rotation, which was respectively out of phase
      (condition A) or in-phase (condition B) with head rotation. In a few instances
      the peak amplitude of neck rotation was increased to 5 degrees. In the first
      experimental condition A, the gain of the VSR (tested every 10-15 min)
      progressively increased, starting from the first hour of out of phase neck
      vestibular stimulation to reach, on average, 241% of the control value at the end
      of the third hour of stimulation. On the other hand, in the second experimental
      condition B, the mean gain of the VSR first decreased to 82% during the first
      hour of in-phase neck-vestibular stimulation, but then increased to 165% of the
      corresponding control during the last hour of recording. In other experiments an
      adaptive increase in gain of the pure VSR occurred during a sustained (3-h)
      period of selective roll tilt of the whole animal, but it was less consistent
      and, on average, smaller in amplitude than that obtained during out of phase neck
      vestibular stimulation. The adaptive changes in gain of the VSR described above
      were not associated with changes in the phase angle of the responses, and were
      also observed during the post-adaptation period. Further experiments indicated
      that the gain of the N-VSR, i.e. of the EMG responses to combined neck-vestibular
      stimulation, displayed a prominent adaptive increase during the sustained out of
      phase stimulation, but not during the in phase stimulation.

PMID- 8134264
TI  - Membrane rectification in single smooth muscle cells from the rat tail artery.
AB  - Membrane rectification to depolarization was studied by voltage recording with
      patch electrodes in freshly isolated cells from the rat tail artery. Injection of
      depolarizing currents elicited electrotonic potentials that developed with a
      single-exponential time course (time constant of 94.8 ms). When the cell was
      depolarized beyond -30 mV, delayed rectification was observed. A second type of
      rectification, characterized by oscillations, was observed when the cell was
      depolarized positive to +30 mV. The threshold of this rectification and the
      oscillations were sensitive to changes in intracellular Ca2+. Delayed
      rectification was more sensitive to 4-aminopyridine but more resistant to
      tetraethylammonium and charybdotoxin than the Ca(2+)-sensitive rectification. A 4
      aminopyridine-sensitive outward current (IK,dr) with a threshold of around -30 mV
      and a second Ca(2+)-sensitive outward current (IK,Ca) activated at around +30 mV
      were observed from whole-cell voltage clamp recordings. IK,Ca was blocked by
      tetraethylammonium and charybdotoxin. An 11-pS and a 122-pS channel, having
      characteristics similar to IK,dr and IK,Ca respectively, were identified from
      single-channel recordings. These observations showed how membrane depolarization
      of vascular smooth-muscle cells was regulated by these two populations of K+
      channels under various conditions.

PMID- 8134265
TI  - 4-Aminopyridine-induced synaptic GABAB currents in granule cells of the guinea
      pig hippocampus.
AB  - Sharp-electrode and tight-seal perforated-patch and whole-cell recording
      techniques were used to evaluate K(+)-dependent inhibitory postsynaptic
      potentials (K-IPSPs) and currents (K-IPSCs) induced by the convulsant 4
      aminopyridine (50 mumol l-1) in granule cells of guinea-pig hippocampal slices.
      The responses were recorded in the presence of blockers for glutamatergic and
      GABAA-receptor-mediated synaptic transmission, 6-cyano-7-nitroquinoxaline-2,3
      dione, picrotoxin and bicuculline. The input resistance was much larger
      (approximately 300 M omega) in tight-seal recording than in sharp-electrode
      recording (approximately 100 M omega), but the amplitudes of K-IPSPs recorded at 
      65 mV holding potential were similar in all three recording configurations. The 4
      aminopyridine-induced currents reversed near the K+ equilibrium potential, and
      the reversal potentials shifted with changes in [K+]out or [K+]in as expected for
      a K+ current. Slope conductance measurements indicated a conductance increase
      during the peak of the K-IPSP up to 5 nS (mean 2.4 nS). The peak conductance was
      underestimated in whole-cell recordings unless the pipette contained Cs+.
      Considering the high membrane resistance of granule cells, K-IPSCs induced by 4
      aminopyridine hyperpolarize the cells considerably and thereby are likely to
      contribute to the failure of 4-aminopyridine to induce burst discharges in
      granule cells.

PMID- 8134266
TI  - Calcium buffering in bursting Helix pacemaker neurons.
AB  - Bursting pacemaker neurons of the snail Helix pomatia were voltage-clamped and Ca
      currents in response to depolarizing steps were recorded. Simultaneously, changes
      in intracellular Ca concentrations were measured using the fluorescent dye fura-2
      and a highly sensitive digital camera. Ca influx through voltage-gated channels
      induced a spatially non-uniform increase in intracellular Ca. The Ca signals
      decayed with a time constant of about 5 s. By increasing the concentration of the
      indicator dye, its Ca-buffering capacity was enhanced and Ca transients in
      response to depolarization were diminished. Thereby, the endogenous Ca buffer
      capacity could be determined and was calculated to be about 480 buffered ions for
      every free Ca ion. The buffer capacity did not vary significantly with the amount
      of Ca influx within the range tested, suggesting that the buffer is not saturated
      at Ca concentrations of up to 1 microM.

PMID- 8134267
TI  - Imaging the lamellipodium of migrating epithelial cells in vivo by atomic force
      microscopy.
AB  - Cell locomotion originates at a specific region of the cell surface, the leading
      edge of a migrating cell. Various factors have been proposed to contribute to the
      propulsion of a cell over the substratum. Rapid turnover processes of
      cytoskeletal elements inside the cell and insertion of new plasma membrane at the
      leading edge of the cell permit the extension of a cell in a given direction. Our
      goal was to image in vivo plasma membrane turnover by means of atomic force
      microscopy (AFM) and to resolve dynamic processes at the nanometer level. As an
      experimental model we used migrating kidney cells derived from the Madin-Darby
      canine kidney (MDCK) cell line that was transformed by alkaline stress. These so
      called MDCK-F cells exhibit spontaneous calcium-dependent oscillatory activity of
      plasma membrane potential associated with cell locomotion. We imaged cells during
      migration and observed dynamic invagination processes in the cell surface close
      to the leading edge, indicating internalization of plasma membrane. Invaginations
      were prevented by removal of calcium from the perfusate. During calcium reduction
      plasma membrane uncoupled from the underlying cytoskeleton and lipidic pores with
      diameters of about 30 nm could be disclosed and imaged. This study demonstrates
      that the AFM can readily trace dynamic physiological processes in vivo,
      emphasizing the potential role of calcium in maintaining plasma membrane
      integrity and function.

PMID- 8134268
TI  - Inhibition of omega-conotoxin-sensitive Ca2+ channel currents by internal Mg2+ in
      cultured rat cerebellar granule neurones.
AB  - The effects of changing the intracellular concentrations of either free Mg2+ ions
      ([Mg2+]i) or Mg(2+)-bound adenosine triphosphate ([Mg.ATP]i) on Ca2+ channel
      currents were assessed in cultured rat cerebellar granule neurones using the
      whole-cell patch-clamp technique. Raising [Mg2+]i from 0.06 mM to 1.0 mM
      inhibited Ca2+ channel currents by approximately 50%. The action of omega
      conotoxin GVIA (omega-CgTX), a selective inhibitor of "N"-type Ca2+ channels was
      also investigated. With increasing [Mg2+]i, the proportion of current
      irreversibly blocked by omega-CgTX was reduced, and was negligible (approximately
      5 pA of current) in the presence of [Mg2+]i values of 0.5 mM or greater. Block of
      the omega-CgTX-sensitive current accounted for the reduction in total current by
      concentrations of [Mg2+]i to 0.5 mM. Raising [Mg2+]i had no effect on the rate of
      decay of Ca2+ currents, but did produce a negative shift in current activation,
      possibly due to a non-specific interaction with negative surface charge. Altering
      [Mg.ATP]i from 0.3 to 5.0 mM caused a twofold increase in the size of currents
      without affecting the proportion of current sensitive to omega-CgTX. [Mg2+]i was
      also effective in inhibiting the Ca2+ channel current following potentiation by
      increasing [Mg.ATP]i. These data suggest that omega-CgTX-sensitive current in
      these cells is selectively inhibited by internal Mg2+ whereas both omega-CgTX
      sensitive and -resistant components of current are potentiated by internal
      Mg.ATP. The mechanism by which Mg2+ inhibits "N"-type channels is unclear, but
      may involve an open channel block.

PMID- 8134269
TI  - Tight-junction tightness of Necturus gall bladder epithelium is not regulated by
      cAMP or intracellular Ca2+. I. Microscopic and general electrophysiological
      observations.
AB  - Following the publications by Duffey et al. [Nature 294:451 (1981)] and Palant et
      al. [Am J Physiol 245: C203 (1983)] it is generally accepted that tight-junction
      tightness of Necturus gall bladder epithelium is up-regulated by cAMP-mediated
      and Ca(2+)-mediated stimulation. This conclusion was mainly based on observed
      increases in transepithelial resistance (Rt). However, since in leaky epithelia
      Rt cannot be simply equated with the tight junction resistance (Rj), but may
      include large contributions from the lateral space resistance (Rlis), we asked
      whether the observed increases in Rt resulted indeed from Rj or whether Rlis also
      increased. The experiments were performed on Necturus gall bladders using
      forskolin or the Ca2+ ionophore A23187 as stimulants. Forskolin (2 mumol/l) had a
      biphasic effect. In the first 5 min Rt decreased from 128 +/- 13 to 119 +/- 14
      omega cm2 (P < 0.05, n = 10) which probably reflects stimulation of an apical
      cell membrane Cl- conductance (see accompanying paper). Subsequently Rt increased
      in approximately 30 min to 184 +/- 20 omega cm2 and then remained fairly
      constant. Simultaneously the lateral spaces collapsed. If the spaces were now
      transiently opened by passing mucosa-positive direct current across the
      epithelium, Rt fell transiently to 111 +/- 7 omega cm2, but returned gradually to
      its elevated level when the spaces collapsed again. When the spaces were
      constantly dilated by a serosa-positive hydrostatic pressure of 1 cm H2O,
      forskolin neither affected the space width nor increased Rt, and current passage
      was virtually ineffective, although the cells depolarized in response to
      forskolin as usual.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134270
TI  - Tight-junction tightness of Necturus gall bladder epithelium is not regulated by
      cAMP or intracellular Ca2+. II. Impedance measurements.
AB  - In the preceding publication we have reported that, contrary to the prevailing
      opinion in the literature, the tight-junction tightness of Necturus gall bladder
      epithelium is not up-regulated by cAMP-mediated or by Ca(2+)-mediated
      stimulation. This conclusion was based on our observation that the stimulant
      induced increase in transepithelial resistance (Rt) occurred only when the
      lateral intercellular spaces were allowed to collapse, which suggested that the
      increase reflected primarily or exclusively the increasing resistance of the
      lateral spaces (Rlis) rather than the postulated increase in tight-junction
      resistance (Rj). An alternative explanation could have been that the constancy of
      Rt after space dilatation reflected an increase Rj that was masked by a
      concomitant fall in apical and basolateral cell membrane resistances Ra and Rbl.
      To decide between those possibilities we have performed impedance measurements
      with transepithelial and intracellular microelectrodes on Necturus gall bladder
      epithelium. Applying previously developed analysis procedures, the measurements
      readily showed that elevation of intracellular Ca2+ concentration increased Rlis,
      but left Rj as well as Ra and Rbl quasi constant. Experiments with forskolin,
      theophylline or isobutylxanthine, on the other hand, were less clear. These
      stimulants activated an apical Cl- conductance, which drastically reduced Ra and
      apparently caused low-frequency polarization effects that could not be accounted
      for by the classical epithelial equivalent circuit. After elimination of the
      polarization phenomena by uni- or bilateral substitution of Cl- by isethionate or
      sulphate, however, we were able to demonstrate that Rj remains constant under
      cAMP-mediated stimulation irrespective of whether the lateral spaces are kept
      open or are allowed to collapse. We conclude that the tight-junction resistance
      of Necturus gall bladder epithelium is not controlled by intracellular Ca2+ or by
      cAMP-mediated stimulation.

PMID- 8134271
TI  - ATP-sensitive potassium channels are modulated by intracellular lactate in rabbit
      ventricular myocytes.
AB  - During myocardial ischemia, increased anaerobic glycolysis results in the
      accumulation of large amount of intracellular lactate. Effects of lactate on the
      ATP-sensitive potassium (KATP) channels were examined in rabbit ventricular
      myocytes, using the inside-out patch-clamp technique. Millimolar concentrations
      of lactate, applied to the cytosolic side of the patch membrane, induced openings
      of the KATP channel. This effect was inhibited by 0.1 mM glybenclamide. Lactate
      induced openings of the channel were increased in a dose-dependent fashion. In
      dose-response relation for lactate, Kd (the lactate concentration producing half
      maximal activation) and n (Hill coefficient) were 20 mM and 1.3, respectively (n
      = 5). Activation of KATP channels by lactate occurred even in the presence of 2
      mM ATP. Lactate also caused a significant increase in Ki, the ATP concentration
      causing half-maximal inhibition, from 70 microM in control (n = 7) to 232 microM
      (n = 5). From the above results it could be concluded that intracellular lactate
      modulate KATP channels directly and such modulation may resolve the discrepancy
      between the low Ki in excised membrane patches and high levels of intracellular
      ATP concentration during myocardial ischemia or hypoxia.

PMID- 8134272
TI  - Differential effects of tamoxifen and I- on three distinguishable chloride
      currents activated in T84 intestinal cells.
AB  - The whole-cell mode of the patch-clamp technique has been used to monitor ionic
      currents in T84 colonic carcinoma cells. The cells were stimulated by either a
      cAMP cocktail, ionomycin or hypotonicity. Sizeable currents with distinct
      kinetics were observed after the stimulation with the different agonists. These
      kinetically distinct Cl- currents also presented a differential sensitivity to
      the anti-oestrogen Tamoxifen and to the halide I-. Tamoxifen only inhibits the
      volume activated Cl- current without affecting the other two. Substitution of
      extracellular Cl- by I- shifted the reversal potential towards more negative
      values both in the hypotonicity and ionomycin activated Cl- currents. The cAMP
      activated current responded to the Cl- substitution by I- with a blockade of both
      outward and inward currents, in addition to the displacement of the zero current
      level towards positive values. Thus, the use of these two simple tools, I- and
      tamoxifen, allows the distinction of Cl- channels in epithelial cells.

PMID- 8134273
TI  - Modification of cardiac Ca2+ release channel gating by DIDS.
AB  - The effects of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) on
      individual cardiac sarcoplasmic reticulum Ca2+ release channels have been
      examined in planar lipid bilayers. A sudden step-like increase in open
      probability (Po) induced by DIDS was observed. At zero holding potential it
      proceeded with an apparent time constant of 84 s and Po was increased 15 times in
      the steady state. Independent of membrane voltage, DIDS induced a long-lived open
      state with tau o = 15 ms at 0 mV and tau o = 5 ms at -50 mV (cis (cytoplasmic)
      side negative). While at 0 mV the modified channel spent most of the time in this
      long-lived state, at -50 mV the occupancy of the long-lived state was very low
      and most openings occurred to the short and medium open state, leading to
      deactivation of the channel to only 2-3 times of control. Voltage-induced changes
      in the activity of modified channels were reversible and proceeded with time
      constants of 14 s for deactivation and 12 s for activation, that is, faster than
      onset of activation by DIDS. As no changes in single channel conductance of the
      channel were observed in the presence of DIDS and its abrupt activating action
      could not be removed, a covalent modification of an amino group residing in the
      gating structure of the channel by DIDS can be considered.

PMID- 8134274
TI  - Amputee population in the Kingdom of Saudi Arabia.
AB  - A 14 year retrospective study was conducted of 3210 amputees who attended during
      the period 1977-1990 at Riyadh Medical Rehabilitation Centre (RMRC), the first
      and the largest rehabilitation centre in the Kingdom of Saudi Arabia. The mean
      age was 30.5 years, male slightly older than female. The mean age of the lower
      limb amputees was 32.6 and of the upper limb amputees 21.8 years. An overall
      predominance of male to female with a ratio of 6.1:1 was observed. Males
      outnumbered females by 5 to 1 in the upper limb and 6.3 to 1 in lower limb
      amputees. The ratio of lower limb to upper limb and multiple limb amputees was
      15:3.7:1. Trauma was the leading cause of upper limb amputations (86.9%). In the
      lower limb, although trauma (52.9%) was the prominent cause, 35.9% was due to
      disease. Major specific causes of trauma were road traffic accidents, machine
      accidents, and falls from height. The most common site of unilateral amputations
      was trans-tibial (45.2%), followed by trans-femoral (21.6%), trans-radial (7.6%),
      partial hand (4.8%), and trans-humeral (4.7%). Comparison with other studies
      shows a higher mean age and fewer trans-tibial amputees than in Australia and
      other Western countries, while studies in Asia show greater similarities to the
      present investigation as regards trauma and disease incidence which occur in
      similar patterns. These patterns of amputee population indicate the demand for
      prosthetic service and provide guidelines for future development.

PMID- 8134275
TI  - Consumer concerns and the functional value of prostheses to upper limb amputees.
AB  - This paper reports a study of 66 upper limb amputees in County Funen, Denmark who
      were visited in their homes by the author. The purpose of the study was to
      evaluate the consumer concerns about their prostheses and to see if these were
      related to cessation of prosthetic use. It was also intended to estimate
      functional levels of both prosthetic users and non-users. The number of amputees
      investigated corresponds to the annual number of persons becoming upper limb
      amputees in Denmark. There were 3 prosthetic systems in use, two active systems
      and one passive system. At review there was a group of 18 amputees which did not
      use a prosthesis at all. It appeared that active and partially active users are
      younger persons with a relatively short time-lapse since amputation. Passive
      users are older persons with a long time-lapse since amputation. Only 4 out of 18
      prosthetic non-users stopped prosthetic use as a consequence of prosthetic
      problems or discomfort. Active prostheses had the highest number of consumer
      problems. Most problems were concerned with the socket, and for the body powered
      prostheses also with the suspension and control system. It was shown that an
      awareness of the amputee's working conditions is important at the fitting stage,
      especially the daily working situation. As a consequence strictly individual
      fitting is needed with attention being given to the manner in which the
      individual will use the prosthesis. This investigation clearly shows that active
      fitting is a worthy effort. In daily living the active users have a superior
      performance over the passive and non-users. It was observed that amputees despite
      many years of training still have problems with activities of daily living,
      particularly in relation to independent functions.

PMID- 8134276
TI  - Clinical evaluation of trans-tibial prosthesis sockets: a comparison between CAD
      CAM and conventionally produced sockets.
AB  - This study is an evaluation, from the patient's point of view, of CAD CAM
      prosthesis sockets compared with conventional sockets. Twenty-two trans-tibial
      amputees were divided into two groups. One group was provided with a CAD CAM
      (CAPOD) socket, the other with a conventionally made one. After one month the
      groups were evaluated with regard to subjective experience, the judgement of a
      prosthetist and a physiotherapist, social variables and objective gait
      parameters. Then the groups switched over to the other type of socket, and after
      another month a new evaluation was performed. The study design was a single-blind
      study. In total 175 variables were evaluated. No difference was found between the
      two types of socket, except for a lower number of terry cloth stockings used in
      the CAD CAM socket. As the standard of conventional prosthetics in Sweden is
      considered to be high, the results were considered as satisfactory. The quality
      of the CAD CAM sockets was at least at the same level as conventionally made
      ones.

PMID- 8134277
TI  - Computer-aided socket design for trans-femoral amputees.
AB  - Computer-aided socket design (CASD) is a technique for the design of prosthetic
      sockets using the advantageous features of computer graphics and calculation.
      This paper describes a computer-aided technique used to design sockets for
      patients with trans-tibial lower limb amputations.

PMID- 8134278
TI  - Fatigue testing of energy storing prosthetic feet.
AB  - This paper describes a simple approach to the fatigue testing of prosthetic feet.
      A fatigue testing machine for prosthetic feet was designed as part of the
      programme to develop an energy storing prosthetic foot (ESPF). The fatigue tester
      does not simulate the loading pattern on the foot during normal walking. However,
      cyclic vertical loads are applied to the heel and forefoot during heel-strike and
      toe-off respectively, for 500,000 cycles. The maximum load applied was chosen to
      be 1.5 times that applied by the bodyweight of the amputee and the test frequency
      was chosen to be 2 Hz to shorten the test duration. Four prosthetic feet were
      tested: two Lambda feet (a newly developed ESPF), a Kingsley SACH foot and a
      Proteor SACH foot. It was found that the Lambda feet have very good fatigue
      properties. The Kingsley SACH foot performed better than the Proteor model, with
      no signs of wear at the heel. The results obtained using the simple approach was
      found to be comparable to the results from more complex fatigue machines which
      simulate the load pattern during normal walking. This suggests that simple load
      simulating machines, which are less costly and require less maintenance, are
      useful substitutes in studying the fatigue properties of prosthetic feet.

PMID- 8134279
TI  - The neuropathic foot.
AB  - The neuropathic foot is described with relation to cause, presentation,
      dysfunction and identification. The various mechanisms of neuropathic foot
      lesions are outlined--overload, diabetic gangrene, continuous pressure, direct
      injury and cutting and temperature effects. The orthotic treatment of the foot is
      discussed and in particular the importance of proper shoe provision and patient
      education and indoctrination emphasised. The use of plaster casts and
      fenestrations to control pressure distribution is described. Finally results of
      an intensive treatment programme are presented to identify the effect on outcome,
      as measured by delay in amputation.

PMID- 8134280
TI  - [123I-iomazenil- and 99mTc-HMPAO in the diagnosis of focal epilepsies: a
      comparison of untreated and treated patients].
AB  - The purpose of this study was to compare HMPAO- and IMZ-SPECT findings in treated
      and untreated patients with focal epilepsies. We examined 20 patients (untreated
      13; treated 7). All patients had a normal CT and/or MRI scan. In all patients
      both whole-brain activity and regional count density (rcd) were evaluated by
      SPECT. Furthermore, the specific and non-specific binding of IMZ were calculated
      for each ROI and the results of both, treated and untreated patients were
      compared. Our data indicate that the normalized cerebral total binding of IMZ was
      significantly increased in all regions in the group of treated patients (p <
      0.001). In contrast, no difference in the tracer binding was found with HMPAO
      SPECT. We conclude that the difference in the IMZ-binding might be due either to
      exogenous or endogenous factors. In our study IMZ-SPECT had a higher sensitivity
      and a lower specificity in the detection of decreased rcd in areas with EEG
      findings that indicate an epileptogenic focus compared with HMPAO-SPECT.

PMID- 8134281
TI  - [ROC analysis of tumor identification using 201Tl-(I)-chloride and 99mTc-(I)
      hexakis (2-methoxy-2-isobutylisonitrile].
AB  - We investigated tumor detectability of bronchial carcinoma using 201Tl and 99mTc
      MIBI with planar scintigraphy and SPECT. We studied 30 tumor patients and 7
      patients with coronary artery disease in a clinical phase III trial. The lung was
      partitioned into 6 areas, which were read independently, to provide a
      sufficiently large sample of tumor-free reference regions. We calculated the
      statistical power for the comparison of sensitivities at a given specificity of
      95% (TPF-test) to demonstrate that the subdivision of the lung and the
      application of the bivariate bi-normal ROC model allows an objective assessment
      of diagnostic performance even for the small sample size of our study. There were
      no significant differences between 201Tl and 99mTc-MIBI for both observers;
      therefore, no advantage of 99mTc-MIBI over 201Tl for tumor scintigraphy could be
      demonstrated. SPECT was significantly superior to planar scintigraphy and should
      be preferred for tumor detection in the thorax.

PMID- 8134282
TI  - [The diagnosis of clinically silent thyroid disorders].
AB  - Results of tests for thyroid function are presented in two equal observation
      periods. Compared with the first the frequency of TSH-determinations was doubled
      in the second period. Data were taken from non-selected in-patients in a general
      hospital. In connection to clinical information TSH determination served as the
      first laboratory test. Prevalence data of hyperthyroid and hypothyroid
      dysfunction in the patients observed are given. According to controversies in
      health care the efficiency and efficacy of thyroid function tests are discussed.
      In an iodine deficient area TSH-determination uncovers many more thyroid
      dysfunctions in elderly patients than expected clinically. Screening of this risk
      group with TSH in connection with clinical information is an adequate diagnostic
      procedure in an area of mild iodine deficiency.

PMID- 8134283
TI  - Detection of diffuse skeletal lesions by monitoring the kinetics of labeled
      phosphonate.
AB  - A method of detecting of diffuse skeletal involvement in patients with metastatic
      tumors or with metabolic diseases is presented. The study consisted of 31
      patients without bone disease and of 26 selected patients with diffuse skeletal
      involvement. The kinetics of 99mTc-dicarboxypropane diphosphonate (DPD) were
      calculated by monitoring the plasma and urine concentrations up to 5 hours after
      administration. Using these data, the renal clearance as well as the increase in
      urinary excretion of 99mTc-DPD were determined. The results indicate that
      measurement of the quantity of 99mTc-DPD excreted in the urine after 3 hours
      allows a reliable separation of the patients with diffuse skeletal lesions from
      normals. Other calculations such as renal clearance as well as the drop in plasma
      concentration were less sensitive. The test may be performed simultaneously with
      bone scintigraphy without additional radiation burden to the patient.

PMID- 8134284
TI  - [99mTc-generator eluates: effects on the radiochemical purity of the labelling
      products].
AB  - Relatively sensitive kits--which are known for low tin content (HMPAO) or for a
      complicated chemical labelling procedure (MAG3)--were tested for their efficiency
      of labelling with eluates of different generators. The radiochemical purity of
      the labelling products was determined according to the manufacturer's
      instructions (HMPAO: Amersham Buchler, MAG3: Mallinckrodt Diagnostica) after
      adding the 99mTcO4- eluates from the different Tc-generators (Amersham Buchler,
      Mallinckrodt Diagnostica, CIS Biointernational). The radiochemical purity was
      determined by using radioanalytical methods such as high performance liquid
      chromatography, thin layer chromatography, paper chromatography and reversed
      phase chromatography. The quality of the three different generator eluates was
      sufficient for the labelling of HMPAO and MAG3. The small differences in quality
      did not limit the use in nuclear medical routine.

PMID- 8134285
TI  - [A scintigraphic simulated cold nodule caused by a cranial course of the
      subclavian artery and vein].
AB  - A patient who underwent a diagnostic thyroid scan, showed an anechoic area in the
      right caudal lobe by ultrasound. In the thyroid scan this area appeared as a cold
      spot. Coloured duplex ultrasound revealed that this area corresponded to the
      subclavian artery and vein and thus represented a deviation from the normal
      anatomy of these vessels.

PMID- 8134286
TI  - [Scintigraphic display of an ectopic parathyroid adenoma using 99mTc-MIBI--2 case
      reports].
AB  - Radionuclide imaging of the parathyroid gland is used in the preoperative
      localization of parathyroid adenoma. Until recently radionuclide imaging of
      parathyroid tumors was performed using a dual-tracer subtraction technique with
      201TI and 99mTcO4-. As an alternative radionuclide imaging with 99mTc-sestamibi
      (MIBI) has been introduced some years ago. The utility of preoperative
      parathyroid localization lies in its ability to direct surgical exploration,
      particularly of ectopic localizations. We present two cases of parathyroid
      adenoma in which radionuclide imaging with 99mTc-MIBI was successful in detecting
      atypical locations. In the first case remaining primary hyperparathyroidism was
      caused by a mediastinal gland. The second case suffered from a recurrence of
      secondary hyperparathyroidism caused by hyperplasia of the autotransplanted gland
      after removal of all four parathyroid glands.

PMID- 8134287
TI  - [False-positive findings in the 99mTc-MIBI SPECT of left bundle branch block and
      angiographic excluded coronary artery disease].
AB  - In a patient with left bundle branch block exercise/rest SPECT using 99mTc-MIBI
      revealed exercise-induced ischemia. After exclusion of significant coronary
      artery stenosis by angiography early dilated cardiomyopathy was assumed.
      Scintigraphic findings using 99mTc-MIBI SPECT in patients with left bundle branch
      block are discussed.

PMID- 8134288
TI  - [Attenuation effects in 99mTc-MIBI stressed myocardium 360 degree SPECT: a
      comparison of the supine and prone positions].
AB  - Due to the higher photon energy of 99mTc as compared to 201Tl attenuation effects
      are expected to be less prominent in SPECT imaging using 99mTc-labelled
      isonitriles. Reduced 99mTc-MIBI uptake has been observed especially in male
      patients despite low probability of coronary artery disease. 56 patients were
      investigated in prone and supine position after bicycle exercise. Inclusion
      criterium was the identical location of the ROI with maximal tracer uptake in
      prone and supine imaging. In prone position 99mTc-MIBI uptake was significantly
      higher in the posterior wall as compared to supine imaging (p < .001). The
      underlying cause of the apparent increase in tracer uptake of the posterior wall
      was a decrease in count density in the region of maximal uptake (p < .01) while
      the count densities in the posterior wall were unchanged (p = NS). Relative
      uptake values in apical and septal regions of the anterior wall significantly
      decreased in prone imaging. SPECT imaging in prone position is useful in
      minimizing attenuation artifacts. However, because a deterioration in the
      anterior wall cannot be excluded, studies that compare the sensitivities and
      specificities for the different coronary arteries are required before general
      prone imaging can be recommended.

PMID- 8134290
TI  - Enhanced expression of neurotensin/neuromedin N mRNA and products of NT/NMN
      precursor processing in neonatal rats.
AB  - Intestinal levels of immunoreactive neurotensin (iNT) and neuromedin N (iNMN), as
      well as mRNA for the NT/NMN precursor, were elevated during the suckling period
      in rats. While transient expression of NT/NMN was observed at 1-5 days of age in
      the proximal small intestine and colon, NT/NMN levels in the ileum increased to
      peak at 10-20 days of age and then decreased to adult levels. The levels of these
      peptides were not elevated in the central nervous system and pituitary over this
      time period. Chromatographic analyses of jejunoileal extracts indicated that
      large molecular forms of iNT and iNMN were present, constituting approximately
      1.3% of total iNT and approximately 56% of total iNMN, respectively. Treatment of
      the large forms with pepsin, which is known to generate the fully immunoreactive
      peptides, NT(3-13), NT(4-13), and NMN, increased immunoreactivity tenfold (iNT)
      and 1.2-fold (iNMN). Thus, large forms actually constituted approximately 13%
      (iNT) and approximately 60% (iNMN). Based upon its physicochemical properties,
      large molecular iNMN was tentatively identified as a 125 residue peptide with NMN
      at its C-terminus [i.e., rat prepro-NT/NMN(23-147)]. The properties of large
      molecular iNT were most similar to those predicted for the entire precursor
      [i.e., rat prepro-NT/NMN(23-169)]. These results indicate a) that enhanced
      expression of NT/NMN occurs in a tissue-specific manner in rats during the
      suckling period; b) that the pattern of precursor processing in intestine yields
      primarily NT and a large molecular form of NMN.

PMID- 8134289
TI  - Antitumoral cyclic peptide analogues of chlamydocin.
AB  - A series of cyclic tetrapeptides bearing the bioactive alkylating group on an
      epsilon-amino-lysyl function have been examined for their antitumoral activity on
      L1210 and P388 murine leukemia cell lines. One analogue belonging to the
      chlamydocin family and bearing a beta-chloroethylnitrosourea group was found to
      be potent at inhibiting L1210 cell proliferation and had a higher therapeutic
      index than the reference compound bis-beta-chloroethylnitrosourea (BCNU) on the
      in vivo P388-induced leukemia model.

PMID- 8134291
TI  - Contrasting effects of PACAP and carbachol on [Ca2+]i and inositol phosphates in
      human neuroblastoma NB-OK-1 cells.
AB  - The effects of PACAPs on [Ca2+]i were compared to those of carbachol in human
      neuroblastoma NB-OK-1 cells. PACAP(1-27) and PACAP(1-38) increased [Ca2+]i in a
      biphasic manner: a transient rise and a secondary plateau. The transient phase
      reflected the mobilization of [Ca2+]i pool(s) via the inositol phosphate pathway.
      The modest sustained plateau required extracellular Ca2+. Carbachol also
      increased [Ca2+]i in a biphasic manner, but it mobilized intracellular Ca2+
      pool(s) with a higher efficacy than PACAPs, then greatly increased Ca2+ entry,
      this being accompanied by a more marked and prolonged elevation of IP3 and IP4
      than with PACAPs. It is likely that cAMP-mediated phosphorylations due to PACAPs
      facilitated desensitization at the PACAP receptor-phospholipase C level, so that
      there was less Ca2+ handling through PACAP receptors than with muscarinic M1
      receptors.

PMID- 8134292
TI  - Gastrin's trophic effect in the colon: identification of a signaling pathway
      mediated by protein kinase C.
AB  - In previous studies we have reported that gastrin exerts a trophic effect on rat
      colonic epithelial cells in vitro. The effect of gastrin appeared to be mediated
      through a protein kinase C mechanism. In this study, we have characterized the
      role of protein kinase C in the gastrin-induced stimulation. Gastrin, in a time-
      and dose-dependent manner, increased protein kinase C translocation from the
      cytosol to the membrane, an index of enzyme activation. Maximum translocation
      occurred in 1 to 2 min following exposure to gastrin (10(-8) M), before declining
      back to baseline level within 5 min. Gastrin did not change total protein kinase
      C activity in the colonic cells. Staurosporine, an inhibitor of protein kinase C,
      totally abolished the basal as well as the gastrin-stimulated activity of protein
      kinase C. The tumor promoter phorbol 12-myristate 13-acetate also stimulated
      colonic epithelial protein kinase C. However, prolonged treatment of cells with
      phorbol inhibited their subsequent response to gastrin stimulation. The response
      to gastrin was also prevented by the gastrin receptor antagonist proglumide.
      These observations suggest that protein kinase C mediates the stimulatory effect
      of gastrin on colonic epithelial cells, possibly through a receptor mechanism.

PMID- 8134293
TI  - Micropurification and amino acid sequence of beta-casomorphin-8 in milk from a
      woman with postpartum psychosis.
AB  - Milk was obtained from a woman with acute postpartum psychosis and with ongoing
      lactation. Defatted samples were subjected to micropurification and collected
      fractions were analyzed by means of their beta-casomorphin-8 immunoreactivity.
      Immunoreactive material with the same chromatographic properties as synthetic
      human beta-casomorphin-8 was determined by amino acid sequence analysis to be Tyr
      Pro-Phe-Val-Glu-Pro-Ile-Pro. Its molecular mass was determined by fast atom
      bombardment-mass spectrometry to be 962.3 Da. These determinations, which
      ultimately identify the immunoreactive material as human beta-casomorphin-8,
      represent the first structural identification of a beta-casomorphin peptide from
      a body fluid.

PMID- 8134294
TI  - Gastrin and cholecystokinin in the Eastern Grey kangaroo, Macropus giganteus
      giganteus.
AB  - Gastrin and CCK are believed to have a common ancestor. The gastrin structure has
      probably evolved from CCK-like peptides at a stage later than the amphibians. To
      trace the evolution of gastrin and CCK we have determined their structures in an
      Australian marsupial, the Eastern Grey kangaroo. The brain CCK was identical to
      CCK-8 of most mammals. The larger form of kangaroo gastrin was a 33mer with the
      sequence pELHPQDLPHLMTDLSKKKGPWQEEDAAY(SO3)GWMDF-NH2. The 11 italic residues
      indicate differences from human gastrin. Gastrin-15 and gastrin-16 comprised
      about 70% of the total immunoreactivity and resulted from cleavage after the
      second and third residue, respectively, of the unusual tribasic cleavage site.
      The smaller forms of kangaroo gastrin differ from most other mammalian gastrins
      in that the N-termini are not blocked with a pyroGlu moiety. Unlike other
      gastrins, kangaroo gastrin is more than 95% sulfated. The present study indicates
      that the gastrin structure, as defined by having a Tyr at position 6 from the C
      terminus, evolved before the marsupials diverged from the other mammals 130
      million years ago.

PMID- 8134295
TI  - Characterization of beta-endorphin- and alpha-MSH-related peptides in rat heart.
AB  - POMC-derived peptides and mRNA have been identified in heart tissue, although
      POMC processing has not been fully characterized. In the present study, we found
      that beta-lipotropin and ACTH were localized in rat heart, although they were
      almost entirely converted to beta-endorphin- and alpha-MSH-related peptides. Ion
      exchange HPLC analysis revealed that beta-endorphin(1-31) was further processed
      to alpha-N-acetyl-beta-endorphin(1-31), which comprised 35.9 +/- 0.1% of total
      immunoreactivity, and smaller amounts of beta-endorphin(1-27), beta-endorphin(1
      26), and their alpha-N-acetylated derivates. The predominant alpha-MSH
      immunoreactive peptides coeluted with alpha-MSH and N,O-diacetyl-alpha-MSH by
      reverse-phase HPLC, although small amounts of ACTH(1-13)-NH2 were also present.
      Thus, multiple forms of beta-endorphin and alpha-MSH are localized in rat heart.
      beta-Endorphin(1-31) is a minor constituent, however, indicating that nonopioid
      beta-endorphin peptides predominate.

PMID- 8134296
TI  - VIP receptors on canine submucosal synaptosomes.
AB  - The present study characterized [125I]VIP binding to synaptosomes from the
      submucosa of canine small intestine. Studies of saturation, competition binding,
      and kinetic studies revealed high- and low-affinity binding sites. Studies with
      GTP-gamma-S and cholera toxin suggested that the receptor was coupled to a G
      protein, possibly Gs. Competition with VIP analogs suggested that the N-terminal
      end of the molecule played the major role in determining affinity and that this
      receptor was for VIP, not PACAP. Cross-linking VIP to the receptor revealed a
      single peptide (M(r) congruent to 60,000). We suggest that VIP may act to
      modulate mediator release from enteric nerve endings.

PMID- 8134297
TI  - Distribution and characterization of motilin receptors in the cat.
AB  - We demonstrate binding of [125I][Nle13-po]motilin to homogenates of cat gastric
      and small intestinal, but not to colonic smooth muscle tissue. The density was
      (Bmax in fmol/mg protein): 0 (fundus); 12 +/- 2 (corpus); 22 +/- 3 (antrum); 55
      +/- 12 (duodenum); 44 +/- 10 (jejunum); 17 +/- 1 (ileum); 0 (colon). A
      significant (p < 0.05) difference was found between the dissociation constant for
      motilin in the stomach (pKd = 8.84 +/- 0.06) and in the small intestine (pKd =
      8.58 +/- 0.08). The motilides erythromycin-A (EM-A), EM-523, and EM-A N-oxide
      displaced labeled [Nle13-po]motilin bound to cat duodenal receptor with potencies
      (pKd) of 5.47 +/- 0.23, 7.60 +/- 0.24, and < 4.3, respectively. Studies with
      [Leu13-po]motilin fragments showed that the N-terminus of motilin interacts with
      the receptor. In the tissue bath, duodenal strips mounted in the longitudinal
      direction responded to motilin, EM-523, and EM-A (pEC50: 8.29 +/- 0.08; 7.12 +/-
      0.12; 5.99 +/- 0.15). The compounds had a comparable intrinsic activity (83 +/-
      3%; 80 +/- 5%; 82 +/- 5% of the response to ACh), which was unaffected by
      atropine, TTX, hexamethonium, and zacopride but reduced by verapamil and calcium
      free medium. Cat stomach and small intestine possess smooth muscle motilin
      receptors, which have comparable properties as those found in man and in rabbit.

PMID- 8134298
TI  - Peptide YY stimulates circular muscle contractions of the isolated perfused
      canine ileum by inhibiting nitric oxide release and enhancing acetylcholine
      release.
AB  - Peptide YY (PYY) and neuropeptide Y (NPY), infused into the quiescent isolated
      perfused canine ileum, dose-dependently increased phasic activity of the circular
      muscle and decreased tonic output of immunoreactive vasoactive intestinal peptide
      (VIP) in the venous effluent. The contractions subsided before the prolonged
      inhibition of VIP output. Motor excitation by PYY, an abundant neuropeptide in
      this tissue, was reduced by blockade of muscarinic or nicotinic receptors, or
      inhibition of nitric oxide (NO) synthase, despite continued inhibition of VIP
      output. A combination of atropine and hexamethonium eliminated the PYY-induced
      decrement in VIP output and left motor excitation unchanged. Blockade of NO
      synthase eliminated motility increases under these conditions. Intracellular
      microelectrode recordings of myenteric plexus-free circular muscle strips found
      no effect of NPY on the resting membrane potential, or on the field stimulation
      induced inhibitory junction potential. Inhibition of VIP release plays no
      essential role in changing motility. These results suggest that PYY/NPY induce
      motility by stimulating release of acetylcholine and inhibiting NO release at a
      locus proximal to but not on nerve terminals.

PMID- 8134299
TI  - Sympathetic thyroidal vasoconstriction is not blocked by a neuropeptide Y
      antagonist or antiserum.
AB  - Sympathetic nerve fibers to thyroid blood vessels contain both norepinephrine
      (NE) and neuropeptide Y (NPY). To assess the involvement of endogenous NPY in the
      sympathetic neural control of thyroid blood flow, appropriate doses of a
      selective NPY antagonist, alpha-trinositol, and an NPY antiserum (NPY-AS) were
      used during cervical sympathetic trunk stimulation in anesthetized rats. During
      all experiments, thyroid blood flow was continuously monitored by laser Doppler
      blood flowmetry. Neither alpha-trinositol nor NPY-AS blocked the thyroidal
      vasoconstriction evoked by either the first or second stimulation of the cervical
      sympathetic trunks. Our results suggest that NPY is not involved either directly
      or indirectly during acute sympathetic vasoconstriction in the rat thyroid gland.

PMID- 8134300
TI  - Parathyroid hormone binding sites in the brain.
AB  - Parathyroid hormone (PTH) has been shown to have actions within the brain,
      suggesting the presence of central PTH receptors. This possibility was examined
      by determining the binding of 125I-labeled [Nle8,18,Tyr34]bovine PTH to the
      plasma membranes of rat and rabbit brains. Specific binding of the tracer to
      membranes of the whole brain was time and tissue dependent, and was greater with
      membranes from the hypothalamus than with membranes from the cerebellum,
      cerebrum, or brain stem. The binding of the tracer to rat hypothalamic membranes
      was saturable and competitively displaced by unlabeled PTH(1-34), PTH(3-34),
      [Nle8,18,Tyr34]PTH(1-34), and by PTH-related protein, indicating the presence of
      a single class of high-affinity (dissociation constant = 2-5 nM), low-capacity
      (maximum binding capacity, Bmax = 110-250 fmol/mg protein) binding site. The
      binding of radiolabeled PTH to these sites was not displaced by unrelated
      peptides of comparable molecular size (calcitonin, calcitonin-gene related
      peptide, adrenocorticotropin). The binding of PTH to these sites did not,
      however, appear to stimulate adenylate cyclase activity, as in peripheral PTH
      target sites. Thus, although these results indicate the presence of PTH receptors
      in the brain, these binding sites have a lower affinity than those in peripheral
      tissues and may utilize a different signal transduction system.

PMID- 8134301
TI  - MK-329 blocks the inhibition of alcohol intake by CCK-8.
AB  - Peripheral administration of sulfated cholecystokinin octapeptide (CCK-8)
      potently reduces alcohol intake, preference, and blood levels in rats. MK-329 (L
      364,718 or Devazepide) acts at peripheral cholecystokinin (CCKA) receptors to
      antagonize CCK-8's physiological and behavioral effects, such as pancreatic
      stimulation and inhibition of feeding. We determined whether CCKA receptor
      blockade would also prevent CCK-8's alcohol satiety effect. Water-deprived female
      and male rats (n = 7 for each) received randomized combinations of
      intraperitoneal injections of MK-329 (0, 100, 200, or 400 micrograms/kg) followed
      by CCK-8 (0 or 4 micrograms/kg). Rats were then given access to 5% w/v ethanol
      for 30 min, followed by 30-min access to water, with food ad lib. MK-329 at all
      doses significantly (p < 0.05) reduced the suppression of alcohol intake and food
      intake by CCK-8. MK-329 alone increased alcohol intake at 400 micrograms/kg, and
      increased food intake, in females and males at 100 and 200 micrograms/kg,
      respectively. We concluded that CCK-8's alcohol and food satiation effects depend
      on specific, peripheral CCKA receptors, and satiation of alcohol consumption and
      drinking-associated feeding reflect an endogenous functional interaction of CCK-8
      with CCKA receptors.

PMID- 8134302
TI  - Binding of a biotinylated neurotrophic ACTH(4-9) analogue, Org 2766, to
      neurofilament-positive cells in primary or cell line cultures.
AB  - To study the putative binding sites of the neurotrophic peptide Org 2766, an
      analogue of ACTH(4-9) [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH], biotinylated forms of
      the peptide were used. After fixation, cultures of rat spinal cord and dorsal
      root ganglia were incubated with 4-10 microM of biotinyl-Org 2766 (b-Org 2766).
      Binding of both N- and C-terminally biotinylated Org 2766 was seen to phase
      bright, round cells with thin processes, but not to flat, orthogonal-shaped cells
      with tapering processes. The b-Org 2766 binding was displaceable by an excess of
      nonbiotinylated Org 2766. Light and electron microscopy showed that the
      biotinylated peptide binds to a cytoplasmatic component as well as to the cell
      membrane. Double-labeling experiments with b-Org 2766 and an antibody (RT-97) to
      a high molecular weight neurofilament protein in dorsal root ganglion cultures
      showed, using fluorescence and confocal scanning laser microscopy, that all b-Org
      2766 binding cells were neurofilament positive. Biotinylated Org 2766 did also
      bind to the neuronally differentiated cells in cultures of the human
      neuroblastoma cell line SK-N-SH, but not to those differentiated into epithelial
      cells. The present data suggest that the neurotrophic peptide Org 2766 binds
      specifically to cell types with neuronal characteristics.

PMID- 8134303
TI  - Vasopressin deficiency and circadian rhythms during food-restriction stress.
AB  - Vasopressin-containing, Long-Evans (LE) rats and vasopressin-deficient,
      Brattleboro (DI) rats were monitored for activity and core body temperature via
      telemetry. Rats were exposed to a 12-12 light-dark cycle and allowed to habituate
      with ad lib access to food and water. The habituation period was followed by an
      experimental period of 23 h of food-restriction stress in which a 1-h feeding
      period was provided during the light cycle. Although both strains of animals
      showed nocturnal activity and temperature rhythms during the habituation period,
      DI rats were more active than LE rats. The DI rats also had a lower body
      temperature in the dark. During the experimental period, both strains exhibited a
      phase shift of activity and body temperature correlating with the presentation of
      food. The DI rats developed a diurnal shift more rapidly than LE rats. The DI
      animals showed a dramatic increase in activity during the light phase and a
      marked decrease in body temperature during the dark phase. The LE animals showed
      a significant attenuation of activity, but maintained both nocturnal and diurnal
      temperature peaks throughout the food-restricted condition.

PMID- 8134304
TI  - Neuronal transmission of hippocampal CA1 neurones is modulated by corticotropin
      like intermediate lobe peptide [CLIP; ACTH(18-39)].
AB  - The study was conducted to test whether CLIP [ACTH(18-39)] influences the
      neuronal transmission and the induction of long-term potentiation (LTP) in the
      hippocampus. The population spike was recorded in the hippocampal CA1 region of
      freely moving rats before and after intracerebroventricular (ICV) administration
      of CLIP in comparison to ACTH and saline (controls). After infusion of CLIP, the
      population spike amplitude (PSA) rose to about 200% of baseline values. After
      reaching this level, it was impossible to induce a further increase of PSA by
      tetanization. However, if the stimulus intensity was reduced to a new baseline
      level, electrically induced LTP could be observed. There were no significant
      changes after infusion of ACTH. Our results indicate that the ICV administration
      of CLIP leads to an enhancement of excitability in the hippocampal CA1 region,
      which might be independent of LTP.

PMID- 8134305
TI  - Two bombesin analogues discriminate between neuromedin B- and bombesin-induced
      calcium flux in a lung cancer cell line.
AB  - We examined the profile of two bombesin (BN) antagonists, (CH3)2CHCO-His-Trp-Ala
      Val-D-Ala-His-Leu-NHCH3] (ICI 216140) and [D-Phe6,des-Met14]BN(6-14)ethylamide
      (DPDM-BN EA), against neuromedin B-induced Ca2+ mobilization in the small cell
      lung cancer (SCLC) line NCI-H345. Neuromedin B (NMB), a BN-like peptide sharing
      sequence homology with ranatensin, elicited a concentration-dependent Ca2+
      release (in part) from intracellular stores. Sequential addition of NMB
      attenuated Ca2+ mobilization. Desensitization occurred between BN and NMB;
      depletion of intracellular Ca2+ is a likely mechanism because thapsigargin
      stimulated Ca2+ release after a maximally desensitizing dose of NMB. ICI 216140
      and DPDM-BN EA competitively inhibited BN-induced Ca2+ transients. In contrast,
      these compounds antagonized NMB-stimulated Ca2+ transients in a noncompetitive
      manner. The pharmacological profiles obtained support receptor heterogeneity for
      BN-like peptides on this SCLC line, underscoring the need for thorough
      examination of dose-response relationships when investigating effects of BN
      analogues on intact cells.

PMID- 8134306
TI  - Identification of gonadotropin-releasing hormone and associated binding
      substances in the blood serum of a holocephalan (Hydrolagus colliei).
AB  - The identity of the gonadotropin-releasing hormone (GnRH) form and the presence
      of GnRH-binding substances in the blood serum of the holocephalan, spotted
      ratfish (Hydrolagus colliei), were investigated. The GnRH-like peptides in the
      serum were identified on the basis of relative hydrophobicity using reverse-phase
      HPLC. [His5,Trp7,Tyr8]GnRH (chicken GnRH-II) was the only GnRH form detected in
      the serum. It has been previously shown to be the only GnRH form in the brain of
      this species. The presence of GnRH-binding substances was inferred by anomalous
      HPLC elution of GnRH, ultrafiltration behavior, and by the direct binding of
      iodinated GnRH analogues by blood serum components. The mean GnRH concentration
      in the extracted blood serum was 125 +/- 11 pg ml-1 (n = 5) in males and 64 +/-
      48 pg ml-1 (n = 4) and 155 +/- 26 (n = 4) in two separate groups of females.
      Measurement of GnRH in the blood serum is complicated by the presence of GnRH
      binding substances, which may cause the coprecipitation of GnRH during extraction
      with organic solvents. The high concentration of GnRH and the presence of GnRH
      binding substances suggest that systemic blood is the route by which GnRH reaches
      the gonadotropes and/or that GnRH may have a hormonal role in H. colliei.

PMID- 8134307
TI  - A common precursor to neurotensin and LANT6 and its differential processing in
      chicken tissues.
AB  - Antisera towards neurotensin (NT) and the structurally related peptide, LANT6,
      were used to characterize immunoreactive peptides and proteins in extracts of
      chicken tissues. A 17 kDa protein was identified by Western blotting as a
      potential precursor to NT and LANT6. However, the posttranslational processing of
      this common precursor appeared to be tissue specific, giving rise to
      disproportionate amounts of NT and LANT6, along with varying expression of a
      large molecular LANT6 (M(r), 15 kDa). The intestinal cells containing
      immunoreactive NT, LANT6, and large molecular LANT6 behaved similarly during
      fractionation by size and density. These activities also banded together in
      particles resembling vesicles during centrifugation of isotonic homogenates of
      tissue. These results suggest that chicken NT and LANT6 are biosynthesized as
      parts of the same precursor, the processing of which can give rise to a variety
      of products stored within secretory vesicles.

PMID- 8134308
TI  - Evidence that enzymatic conversion of N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala
      Phe-p-aminobenzoate, a specific inhibitor of endopeptidase 24.15, to N-[1(R,S)
      carboxy-3-phenylpropyl]-Ala-Ala is necessary for inhibition of angiotensin
      converting enzyme.
AB  - N-[1(R,S)-Carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) is a
      potent, substrate-related, specific inhibitor of endopeptidase 24.15, an enzyme
      involved in the metabolism of bioactive peptides including bradykinin,
      neurotensin, and proenkephalin, and prodynorphin-derived enkephalin precursors.
      The observation that this inhibitor causes a pronounced decrease in blood
      pressure after intravenous infusion into normotensive rats posed the question of
      the mechanism of this hypotensive response. It was suggested previously that cFP
      AAF-pAB is an inhibitor of angiotensin converting enzyme (ACE) and that this
      function can account for the hypotensive response to the inhibitor. We present
      here evidence that cFP-AAF-pAB has no intrinsic ACE-inhibitory activity. The
      previously observed inhibition is shown to be dependent on cleavage of the Ala
      Phe bond in the inhibitor by endopeptidase 24.11 (enkephalinase, EC 3.4.24.11), a
      contaminant of some ACE preparations.

PMID- 8134309
TI  - Alpha-neo-endorphin-like immunoreactivity in the cat brain stem.
AB  - This paper examines the distribution of fibers and cell bodies containing alpha
      neo-endorphin in the cat brain stem by using an indirect immunoperoxidase
      technique. A high or moderate density of immunoreactive cell bodies was found in
      the superior central nucleus, nucleus incertus, dorsal tegmental nucleus, nucleus
      of the trapezoid body, and in the laminar spinal trigeminal nucleus, whereas a
      low density of such perikarya was observed in the inferior colliculus, nucleus
      praepositus hypoglossi, dorsal nucleus of the raphe, nucleus of the brachium of
      the inferior colliculus, and in the nucleus of the solitary tract. The highest
      density of immunoreactive fibers was found in the substantia nigra, dorsal motor
      nucleus of the vagus, nucleus coeruleus, lateral tegmental field, marginal
      nucleus of the brachium conjunctivum, and in the inferior and medial vestibular
      nuclei. These results indicate that alpha-neo-endorphin is widely distributed in
      the cat brain stem and suggest that the peptide could play an important role in
      several physiological functions, e.g., those involved in respiratory,
      cardiovascular, auditory, and motor mechanisms.

PMID- 8134310
TI  - Chronic intracerebroventricular infusion of the antiopioid peptide, Phe-Leu-Phe
      Gln-Pro-Gln-Arg-Phe-NH2 (NPFF), downregulates mu opioid binding sites in rat
      brain.
AB  - Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF), an endogenous mammalian antiopioid
      peptide, has been shown by other laboratories to attenuate the acute
      antinociceptive effects of morphine, the development of morphine tolerance, and
      naloxone-induced withdrawal in morphine-dependent rats. The present study
      determined the effect of chronic NPFF on mu opioid receptors and mRNA for the
      endogenous opioids dynorphin and enkephalin. Rats received ICV infusions of
      either saline or NPFF (5 micrograms/h) for 13 days via Alzet 2002 osmotic
      minipumps. Homogenate binding studies, which used whole brain membranes,
      demonstrated that NPFF decreased the Bmax of mu binding sites (labeled by [3H][D
      Ala2-MePhe4,Gly-ol5]enkephalin) from 262 +/- 12 to 192 +/- 12 fmolmg protein, and
      increased the Kd from 1.1 to 2.3 nM. Quantitative receptor autoradiography and in
      situ hybridization experiments were conducted with sections collected at the
      level of the striatum. The density of mu opioid binding sites labeled by [3H][D
      Ala2-MePhe4,Gly-ol5]enkephalin was decreased in all brain areas measured except
      the corpus callosum, and there was no change in dynorphin mRNA or enkephalin mRNA
      in the caudate, the nucleus accumbens, or the ventral pallidum. Rats chronically
      administered ICV morphine sulfate (20 micrograms/h) for 14 days developed
      tolerance to morphine and a low degree of dependence, as measured by naloxone
      precipitated withdrawal. Chronic administration of NPFF concurrently with
      morphine sulfate did not significantly alter naloxone-induced withdrawal signs or
      the development of morphine tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134311
TI  - Selective labeling of kappa 2 opioid receptors in rat brain by [125I]IOXY:
      interaction of opioid peptides and other drugs with multiple kappa 2a binding
      sites.
AB  - Recent studies from our laboratory resolved two subtypes of the kappa 2 binding
      site, termed kappa 2a and kappa 2b, 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). 6 beta
      Iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan (IOXY), an
      opioid antagonist that has high affinity for kappa 2 sites, was radioiodinated to
      maximum specific activity (2200 Ci/mmol) and purified by high pressure liquid
      chromatography and used to characterize multiple kappa 2 binding sites. The
      results indicated that [125I]IOXY, like [3H]bremazocine, selectively labels kappa
      2 binding sites in rat brain membranes pretreated with BIT and FIT. Using 100 nM
      [D-Ala2-MePhe4,Gly-ol5]enkephalin to block [125I]IOXY binding to the kappa 2b
      site, two subtypes of the kappa 2a binding site were resolved, both in the
      absence and presence of 50 microM 5'-guanylyimidodiphosphate. Viewed
      collectively, these results provide further evidence for heterogeneity of the
      kappa opioid receptor, which may provide new targets for drug design, synthesis,
      and therapeutics.

PMID- 8134312
TI  - Role of calcium in the bombesin-induced intestinal CCK release in rats.
AB  - In the isolated vascularly perfused rat duodenojejunum, vascular infusion of
      bombesin (100 nM) provoked an early, transient (6 min) release of CCK (500% of
      basal), followed by a sustained response (400% of basal). The calcium chelator
      EGTA (2 mM) reduced the early peak and abolished the second phase of CCK release.
      A similar variation was evoked by verapamil (10 microM), whereas diltiazem (100
      microM), nifedipine (50 microM), and omega-conotoxin (100 nM) had no significant
      effect. It is concluded that bombesin-induced CCK release from rat intestine is
      dependent on the availability of extracellular calcium and on the activation of
      calcium channels sensitive to blockers of the phenylalkylamine family.

PMID- 8134313
TI  - Spinal and peripheral modulation of gastric acid secretion and arterial pressure
      by neuropeptide Y, peptide YY, and pancreatic polypeptide in rats.
AB  - Spinal and peripheral modulation of pentagastrin-stimulated gastric acid
      secretion by the pancreatic polypeptide-fold (PP-fold) peptides, neuropeptide Y
      (NPY), peptide YY (PYY), and pancreatic polypeptide (PP), in urethane
      anesthetized rats was evaluated. Neuropeptide Y, PYY, and PP (400 pmol) were
      administered via intravenous (IV) and intrathecal (IT) injections. The alpha 2
      antagonist, yohimbine, was used to evaluate the role of the alpha 2 adrenergic
      receptors in the modulation of pentagastrin-stimulated gastric acid secretion by
      NPY, PYY, and PP. Peptide YY and PP (IV) rapidly increased pentagastrin
      stimulated gastric acid secretion. Peptide YY and PP (IT) increased pentagastrin
      stimulated gastric acid secretion following administration into the thoracic (T8
      T10) region of the spinal cord. The alpha 2 adrenergic receptor antagonist,
      yohimbine, did not modify the increases in pentagastrin-stimulated gastric acid
      secretion following PYY and PP (IV or IT) administration. Neuropeptide Y (IT)
      decreased pentagastrin-stimulated gastric acid secretion. However, in the
      presence of alpha 2 adrenergic receptor blockade, pentagastrin-stimulated gastric
      acid secretion was potentiated by NPY (IT) administration. Therefore, the
      inhibitory effect of NPY (IT) on pentagastrin-stimulated gastric acid secretion
      required the activation of alpha 2 adrenergic receptors in the spinal cord of
      rats. Mean arterial blood pressure (MAP) was increased immediately following NPY
      and PYY (IV) administration. During the same time period, PP (IV) decreased MAP
      in anesthetized rats. Mean arterial blood pressure was rapidly increased by NPY
      and PYY (IT) in anesthetized rats. The increase in MAP following PYY (IT) was
      partially attenuated in the presence of yohimbine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8134314
TI  - Effect of atrial natriuretic peptide on bronchial tone in anesthetized rabbits.
AB  - The effect of atrial natriuretic peptide (ANP) on histamine-induced
      bronchoconstriction was studied in vivo (in normoxic and in hypoxic rabbits) and
      in vitro. Thirty-two anesthetized rabbits, spontaneously breathing room air or
      10% O2, received infusions of ANP (20, 40, or 80 ng/min/kg normoxia; 20 ng/min/kg
      hypoxia) or the vehicle for 100 min. After 75 min of ANP infusion,
      bronchoconstriction was induced inhaling histamine; respiratory resistance (Rrs)
      was measured prior to and until 20 min posthistamine. The results show that the
      histamine-induced increase in Rrs was significantly reduced by ANP 80 ng/kg/min
      in normoxia, and by ANP 20 ng/kg/min in hypoxia. In vitro, ANP had no effect on
      tracheal and bronchial smooth muscle precontracted with histamine or
      acetylcholine. These results show that ANP can decrease a histamine-induced
      bronchoconstriction in vivo but not in vitro, suggesting an indirect mechanism of
      action.

PMID- 8134315
TI  - Characterization of the oligosaccharide moiety of VIP receptor from the human
      pancreatic cell line BxPC-3.
AB  - The human pancreatic cell line BxPC-3 displays two classes of binding sites with
      high and low affinity for VIP. The order of potency of VIP-related peptides in
      inhibiting either [125I]VIP or [125I]N-AcPACAP27 binding and in stimulating cAMP
      production was typical of the human VIP receptor. By combining affinity labeling
      with glycosidase treatments, we have characterized the VIP receptor as a M(r) =
      68,200 glycoprotein, consisting of a M(r) = 39,300 polypeptide core with at least
      three N-linked oligosaccharide chains. In addition, our results revealed the
      presence of a low amount of sialic acid residues in the carbohydrate moiety of
      receptor.

PMID- 8134316
TI  - Endogenous opiates: 1992.
AB  - This paper is the fifteenth installment of our annual review of research
      concerning the opiate system. It includes papers published during 1992 involving
      the behavioral, non-analgesic, effects of the endogenous opiate peptides. The
      specific topics this year include stress; tolerance and dependence; eating;
      drinking; gastrointestinal and renal function; mental illness and mood; learning,
      memory, and reward; cardiovascular responses; respiration and thermoregulation;
      seizures and other neurological disorders; electrical-related activity; general
      activity and locomotion; sex, pregnancy, and development; immunological
      responses; and other behaviors.

PMID- 8134317
TI  - A low-literacy skin care manual for spinal cord injury patients.
AB  - Most patient education materials are written at least two grade levels above the
      average grade achievement of health care consumers. This paper describes the
      development of a patient education manual for people with low literacy skills.
      The manual provides information about pressure ulcer prevention for patients with
      spinal cord injuries. Educational principles related to literacy skills were
      applied to produce a manual at the fifth-grade reading level.

PMID- 8134318
TI  - Performance objectives for the self-management of cystic fibrosis.
AB  - Performance objectives for the self-management of cystic fibrosis (CF) were
      developed and subjected to a two-stage content validation. A multidisciplinary
      team of health care professionals generated a list of 149 medical and adjustment
      performance objectives. Behaviors included monitoring symptoms and judging their
      significance, treating symptoms and communicating with health care providers
      about symptoms and treatment plans. In the first stage a panel of experts in the
      medical and behavioral aspects of CF rated each behavior. In general, the eleven
      panelists rated the 149 behaviors as somewhat important or important (mean 2.6,
      S.D. 0.17, on a 3-point scale). In the second stage, 84 of 155 CF center
      directors rated all behaviors as somewhat important or important (mean 2.9, S.D.
      0.23). Specific behaviors related to medical regimens were more consistently
      rated as important than were those related to psychosocial adjustment. The
      performance objectives provide a framework for developing and evaluating health
      education programs for the self-management of CF in order to promote optimum
      health and adjustment.

PMID- 8134319
TI  - The potential of computers in patient education.
AB  - Typical computer programs for patient education are didactic and fail to tailor
      information to an individual's specific needs. New technology greatly enhances
      the potential of computers in patient education. Computer-assisted instruction
      programs can now elicit information from users before leading them through
      problem-solving exercises. New authoring systems enable health professionals to
      develop their own programs. The capacity to elicit and report back information
      about factors that influence patients' health behaviors give the newest computer
      programs one of the strengths of face-to-face patient counseling: the ability to
      tailor an educational message for an individual patient. These programs are not
      intended to replace but rather to enhance personal interaction between providers
      and patients. This article describes the advantages of using computers for
      individualizing patient education and assessing trends across groups of patients.
      Innovative programs and features to look for in programs and equipment selection
      are also described.

PMID- 8134320
TI  - The information-seeking behavior of cancer outpatients: a description of the
      situation.
AB  - The information-seeking behavior of cancer outpatients has been studied with the
      purpose of collecting data for the development of an educational intervention:
      stimulating communication between cancer outpatients and their specialists. The
      intention to seek information, the realization of the intention and the reasons
      for not realizing it are measured with several qualitative and quantitative
      methods: written questionnaires (n = 60, n = 18), audio records (n = 40) and
      focus group interviews (n = 19). Not every patient (58%) intends to discuss
      topics of illness and treatment with the specialist. Possible incentives to plan
      a discussion with the specialist are experienced uncertainty, fear and
      dissatisfaction with information received. In 22% of cases cancer outpatients do
      not realize their intention, and in 25% of cases the realization of the intention
      is due to the initiative of the specialist or the patient's companion. The
      information-seeking behavior of cancer outpatients appears to be influenced by
      several factors, including patients' needs, values and beliefs; unexpected
      situations; patients' skills; and specialists' and companions' behavior.

PMID- 8134321
TI  - Educational and behavioral strategies related to knowledge of and participation
      in an exercise program after cardiac positron emission tomography.
AB  - The purpose of this research was to determine the difference between educational
      strategies alone and educational plus behavioral strategies on patients'
      knowledge of and participation in an exercise program aimed at modifying the
      cardiac risk factor of physical inactivity. Educational strategies employed were
      providing verbal and written information, tailoring to individuals' needs, and
      collaborating with patients. Behavioral strategies employed were goal-setting,
      self-monitoring, positive reinforcement and telephone follow-up at 2, 4, 6 and 12
      weeks. Fifty-four subjects without coronary heart disease as determined by
      positron emission tomography scanning were randomly assigned to one of the two
      groups. Knowledge, frequency and duration of exercise were evaluated before the
      program and over the telephone 6 and 12 weeks after the education. Repeated
      measures of multivariate analysis of variance demonstrated significant increases
      in knowledge and exercise for both groups. The combination of strategies was more
      effective than educational strategies alone in improving patients' exercise
      frequency at 6 weeks.

PMID- 8134322
TI  - Patient education objectives in Healthy People 2000: policy and research issues.
AB  - The extensive nationwide involvement in the development of year 2000 health
      objectives, and the breadth of the 298 objectives produced, illustrate the scope
      of contemporary public health and preventive medicine in the United States.
      Patient education is an essential element of numerous year 2000 priority targets;
      full accomplishment of the patient education objectives will be influenced by
      several policy issues. This paper discusses special needs in three areas: data
      for decision-making, prevention effectiveness and research gaps. One major data
      issue is difficulty in documenting the existence and scope of patient education,
      and better measurement systems are desirable. A renewed interest in prevention
      effectiveness suggests that patient education would benefit from emphasis on five
      elements of prevention effectiveness: guidelines development; guidelines
      dissemination; demonstrations and technical assistance; monitoring; and research.
      Emerging research needs are identified, with particular focus on quality-of-life
      measurement and on integrated patient education and health communication
      strategies.

PMID- 8134323
TI  - [Vitamin A deficiency and bronchial cancer: prospects for chemoprevention of
      bronchial tumors].

PMID- 8134324
TI  - [Evaluation of a portable device for measuring maximal inspiratory pressure
      (Pimax)].
AB  - Pimax measurement is useful for quantifying the fatigue of the respiratory
      muscles (the "respiratory pump" of the mechanics of respiration), for controlling
      the therapeutic effect of artificial respiration performed at home, and
      assessment of the possibility of relieving a patient from artificial respiration.
      So far, such measurement had required complicated set-ups. A portable alternative
      is now available for Pimax measurement (MPM, distributed by Medanz, Starnberg,
      Germany). In a prospective study we compared the Pimax values measured via the
      mouth pressure measuring instrument under test, with the standard laboratory
      method. Statistical comparison of the measured data yielded a high degree of
      correlation (r = 0.97) with slight scatter of the individual data around the
      identity line. The portable instrument tested in this manner thus represents a
      mobile method yielding reliable Pimax values both on an inpatient and an
      outpatient basis.

PMID- 8134325
TI  - [Reliability of bacteriologic diagnosis of tuberculosis. Results of external
      quality control 1991-1992].
AB  - A report on the results of three proficiency-tests is presented. They were
      performed to test the efficiency of mycobacteriological laboratories. The
      incidence of false test-results varied between samples from 2 to 20%. In each
      survey between 10 and 20% of the participating laboratories arrived at
      unacceptably poor total assessments. The proportion of institutes where lack of
      expert competence can be suspected due to repeated failure in external quality
      tests, was between 3% (microscopy) and 13% (differentiation between tuberculosis
      bacteria and environmental mycobacteria). Reproducibility of good and poor total
      assessments in more than 80% of the laboratories indicates even if a laboratory
      participates in a survey only once, this will already supply quite reliable
      information on the efficiency of that laboratory. Even though many laboratories
      with poor performance in surveys try to improve their standards on their own, it
      is evident from the large number of institutes with repeated poor results, as
      well as from the irregular participation by many institutes in external quality
      tests, that external quality assurance of bacterio-logical tuberculosis
      diagnostics cannot be achieved by proficiency tests alone. Since the provisions
      of the Federal law on epidemics do not bestow sufficient legal competence on the
      health authorities in respect of control of the laboratories, and also because
      eventual sanctions imposed by the sickness insurance bodies cannot be effective
      in all cases, it is at present imperative that treating physicians take
      particularly great interest in the efficiency of the laboratories commissioned by
      them, for their patients' sake.

PMID- 8134326
TI  - [Epidemiologic picture of bronchial cancer].

PMID- 8134327
TI  - [Extreme self-medication: a case report].
AB  - On the background of insufficient allergological diagnostic a case of serious
      cowhair asthma was misinterpreted as intrinsic asthma which led to an extreme
      form of selfmedication. The excessive daily intravenous selfapplication of 2000
      mg theophylline and 24 mg fenoterol per inhalationem for about 4 years was
      tolerated without any serious side effects. The continues smoking of 40
      cigarettes per day may have protected the patient from a toxic dose of
      theophylline. This case report demonstrates the importance of basic diagnostic as
      well as the continuous control of the proposed medication.

PMID- 8134328
TI  - [Maxims in medicine].

PMID- 8134329
TI  - Function of masticatory system after surgical-orthodontic correction of
      maxillomandibular discrepancies.
AB  - Thirty-two subjects were interviewed about their pre- and post-treatment symptoms
      of craniomandibular disorders (CMD) and examined for signs of CMD at follow up 2
      5 years after surgical-orthodontic treatment for maxillomandibular discrepancies.
      Symptoms of CMD were among the main reasons for seeking treatment in 31% of the
      patients. Patients with retrognathic mandibles had significantly more severe
      symptoms than patients with mandibular prognathism before treatment. After
      treatment, the severity of subjective symptoms had decreased for the patients as
      a whole, and significantly in the subjects with originally severe symptoms. Ten
      subjects out of 12 reported a decrease in the occurrence of headache. The
      clinical findings of CMD after surgery were usually mild. The importance of
      occlusal adjustment and rehabilitation as final steps after surgical-orthodontic
      treatment is stressed.

PMID- 8134330
TI  - The Finnish Family Competence Study: young fathers' views on health education.
AB  - The views of fathers of young families on health education were obtained using
      questionnaires issued through Maternity Health Care Clinics and Well-Baby
      Clinics. The present study is part of the Finnish Family Competence Study. The
      first phase of the study included 1,414 fathers whose wives were expecting their
      first baby. Of them, 1,279 returned a questionnaire. In the second phase, at week
      28 of the wife's pregnancy, 1,123 fathers returned a questionnaire. A third
      questionnaire issued when the baby was born was completed by 1,134 fathers. A
      further questionnaire issued three months after the baby's birth was completed by
      1,089 fathers. When the child was three years old, 753 fathers returned a
      questionnaire. Basic educational level, age and occupation were used as
      demographic variables. Backgrounds of respondents were studied using questions on
      the socioeconomic status of the fathers, as well as that of their wives and
      parents, and the locations of respondents' childhood and present homes. Subjects
      were asked comment on health education intended for their children. The
      socioeconomic status and age of the father affected preferences for the content
      and form of the child's health education. In memorizing their childhood
      experience of dental visits, most fathers stated that they had been frightened.
      Attention was not paid in the study to the extent to which the fathers had
      transferred this fear to their children.

PMID- 8134331
TI  - Oral health status in a Finnish village.
AB  - The aim of this study was to describe edentulousness, numbers of remaining teeth,
      dental caries, caries experience, periodontal pockets, and background factors in
      a Finnish village. It was particularly aimed at determining the incidence of
      simultaneous occurrence of untreated caries lesions and periodontal pockets. It
      was carried out in 1988 in Viekijarvi, a village in North Karelia. Half of the
      population was invited to participate in the investigation. Seventy-two percent
      of those invited participated (n = 179). The subjects were examined clinically
      using standard WHO methods and criteria. The subjects were interviewed to
      establish socioeconomical factors and health habits. Thirty-five per cent of
      subjects were edentulous. Numbers of remaining teeth decreased with age, except
      in the age group 55-59 years. Numbers of teeth and edentulousness were strongly
      associated with use of dental services but not with health habits. More than half
      of the dentate population had untreated caries. Of habits affecting health, only
      smoking was associated with caries. Twenty-nine per cent of the dentate
      population had shallow pockets and 7% deep pockets. The occurrence of pockets was
      negatively associated with frequency of handwashing. Only 20% of the dentate
      population were orally healthy. The age group 55-59 years was healthier than the
      younger and older groups.

PMID- 8134332
TI  - Trigeminal foraminal patterns in "skeletal" Class II and Class III adults--a
      radiocephalometric study.
AB  - Radiocephalometric analysis, based mainly on the foramina of the trigeminal nerve
      branches, was applied to three samples of adults, two representing fairly extreme
      profile types, the third representing "normal" dentofacial build. The aim of the
      study was to find out whether the analytical method could be used to
      differentiate between facial types. It appeared that some elements of the method
      had diagnostic powers, and could substitute for traditional methods. Many
      dimensions inspected, however, were fairly similar in all facial types, thus
      suggesting a general basic role of the trigeminal nerve in relation to
      craniofacial structure. Generally speaking, the foraminal pattern was relatively
      stable in "normal" faces, but more variable in deviant faces.

PMID- 8134333
TI  - Comparison of dental arch dimensions in children from southern and northern
      Finland.
AB  - The purpose of this survey was to determine whether children in northern Finland
      had different dental arch dimensions from children in southern Finland. Dental
      casts of 9-year-old healthy children from Helsinki (southern Finland) and from
      Oulu and Sodankyla (northern Finland) were measured. Each group contained 41
      subjects who had received no orthodontic treatment. The children from Sodankyla
      and Oulu had narrower dental arches and greater palatal heights than those from
      Helsinki. The lengths and perimeters of dental arches were significantly shorter
      in the children from Sodankyla than in those from Helsinki. We suggest these
      differences could have resulted from adaptation to different climatic conditions,
      affecting modes of breathing.

PMID- 8134334
TI  - Pharmacogenetics: the slow, the rapid, and the ultrarapid.

PMID- 8134335
TI  - Inducible growth arrest: new mechanistic insights.

PMID- 8134336
TI  - Clues to brain function from bakers' yeast.

PMID- 8134337
TI  - Mapping memory with positron emission tomography.

PMID- 8134338
TI  - Sequence-specific transcriptional activation is essential for growth suppression
      by p53.
AB  - Although several biochemical features of p53 have been described, their
      relationship to tumor suppression remains uncertain. We have compared the ability
      of p53-derived proteins to act as sequence-specific transcriptional (SST)
      activators with their ability to suppress tumor cell growth, using an improved
      growth-suppression assay. Both naturally occurring and in vitro derived mutations
      that abrogated the SST activity of p53 lost the ability to suppress tumor cell
      growth. Additionally, the N- and C-terminal ends of p53 were shown to be
      functionally replaceable with foreign transactivation and dimerization domains,
      respectively, with concordant preservation of both SST and tumor-suppressive
      properties. Only the central region of p53, conferring specific DNA binding, was
      required to suppress growth by such hybrid proteins. The SST activity of p53 thus
      appeared to be essential for the protein to function as a tumor suppressor.

PMID- 8134339
TI  - A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin.
AB  - Sec1 is a hydrophilic protein that plays an essential role in exocytosis from the
      yeast Saccharomyces cerevisiae. Two high copy suppressors of mutations in the
      Sec1 gene, SSO1 and SSO2, were recently identified that encode proteins of the
      syntaxin family. Syntaxin (a T-SNARE), together with SNAP-25 and
      synaptobrevin/VAMP (a T- and a V-SNARE, respectively), is thought to form the
      core of the docking-fusion complex in synaptic vesicle exocytosis. Proteins that
      exhibit similarity to Sec1 were identified in the nervous system of Drosophila
      melanogaster (Rop) and Caenorhabditis elegans (UNC18). Based on the amino acid
      sequence alignment of Sec1, Rop, and UNC18, we have used a PCR-based approach to
      isolate a rat brain cDNA encoding a Sec1 homologue. The cDNA hybridizes to a 3.5
      kb brain-specific mRNA by Northern blot analysis and encodes a protein of 593
      amino acids (rbSec1). Antibodies raised against a central portion of rbSec1
      recognize a 67.5-kDa protein in total homogenates of rat brain but not of
      nonneuronal tissues. When incubated with a Triton X-100 brain extract, rbSec1
      glutathione S-transferase (GST) fusion protein, but not GST protein alone,
      specifically interacts with syntaxin but not with SNAP-25 or synaptobrevin/VAMP.
      We conclude that the function of proteins of the Sec1 family in membrane fusion
      involves an interaction with a T-SNARE.

PMID- 8134340
TI  - Neuroanatomical correlates of encoding in episodic memory: levels of processing
      effect.
AB  - Cognitive studies of memory processes demonstrate that memory for stimuli is a
      function of how they are encoded; stimuli processed semantically are better
      remembered than those processed in a perceptual or shallow fashion. This study
      investigates the neural correlates of this cognitive phenomenon. Twelve subjects
      performed two different cognitive tasks on a series of visually presented nouns.
      In one task, subjects detected the presence or absence of the letter a; in the
      other, subjects categorized each noun as living or nonliving. Positron emission
      tomography (PET) scans using 15O-labeled water were obtained during both tasks.
      Subjects showed substantially better recognition memory for nouns seen in the
      living/nonliving task, compared to nouns seen in the a-checking task. Comparison
      of the PET images between the two cognitive tasks revealed a significant
      activation in the left inferior prefrontal cortex (Brodmann's areas 45, 46, 47,
      and 10) in the semantic task as compared to the perceptual task. We propose that
      memory processes are subserved by a wide neurocognitive network and that encoding
      processes involve preferential activation of the structures in the left inferior
      prefrontal cortex.

PMID- 8134341
TI  - Neuroanatomical correlates of retrieval in episodic memory: auditory sentence
      recognition.
AB  - This study used positron emission tomography (PET) to investigate the
      neuroanatomical correlates of remembering previously experienced events. Twelve
      young healthy adults listened to "old" meaningful sentences which they had
      studied 24 hr previously. As a control task the subjects listened to comparable
      "new" sentences that they had never heard before. Regional cerebral blood flow
      associated with each task was measured by PET scans using 15O-labeled water.
      Comparison (old-sentence task minus new-sentence task) of the PET images revealed
      an extended strip of increased blood flow in the right dorsolateral prefrontal
      cortex (Brodmann's areas 10, 46, and 9) and the anterior portion of area 6. Other
      principal regions of increased blood flow were situated around the left anterior
      cingulate sulcus and bilaterally in the parietal lobes (areas 7 and 40). Major
      decreases in blood flow were situated bilaterally in the temporal lobes (areas
      21, 22, 41, and 42). A high proportion of activity changes seemed to be located
      in the depths of cortical sulci. Increases in blood flow are seen as reflecting
      the operations of a widely distributed neuronal network involving prefrontal and
      parietal cortical regions that subserves the conscious recollection of previously
      experienced events. Decreases in blood flow in the temporal auditory areas are
      interpreted as reflecting auditory priming. The prevalence of sulcal blood-flow
      changes may reflect extensive cortical gyrification; it may also indicate that
      memory-related processes rely on the densely packed neuropil of sulcal regions.

PMID- 8134342
TI  - Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission
      tomography findings.
AB  - Data are reviewed from positron emission tomography studies of encoding and
      retrieval processes in episodic memory. These data suggest a hemispheric
      encoding/retrieval asymmetry model of prefrontal involvement in encoding and
      retrieval of episodic memory. According to this model, the left and right
      prefrontal lobes are part of an extensive neuronal network that subserves
      episodic remembering, but the two prefrontal hemispheres play different roles.
      Left prefrontal cortical regions are differentially more involved in retrieval of
      information from semantic memory and in simultaneously encoding novel aspects of
      the retrieved information into episodic memory. Right prefrontal cortical
      regions, on the other hand, are differentially more involved in episodic memory
      retrieval.

PMID- 8134343
TI  - The kinetics of spontaneous DNA branch migration.
AB  - An important step in genetic recombination is DNA branch migration, the movement
      of the Holliday junction or exchange point between two homologous duplex DNAs. We
      have determined kinetic parameters of spontaneous branch migration as a function
      of temperature and ionic conditions. The branch migration substrates consist of
      two homologous duplex DNAs each having two single-strand tails at one end that
      are complementary to the corresponding single-strand tails of the other duplex.
      Upon rapid annealing of the two duplex DNAs, a four-stranded intermediate is
      formed that has a Holliday junction at one end of the duplexes. Branch migration
      to the opposite end of the duplexes results in complete strand exchange and
      formation of two duplex products. The rate of branch migration is exceedingly
      sensitive to the type of metal ions present. In magnesium, branch migration is
      quite slow with a step time, tau, equal to 300 msec at 37 degrees C.
      Surprisingly, branch migration in the absence of magnesium was 1000 times faster.
      Despite this difference in rates, apparent activation energies for the branch
      migration step in the presence and absence of magnesium are similar. Since metal
      ions have a profound effect on the structure of the Holliday junction, it appears
      that the structure of the branch point plays a key role in determining the rate
      of spontaneous DNA branch migration. We discuss the role of proteins in promoting
      the branch migration step during homologous recombination.

PMID- 8134344
TI  - Abrogation of oncogene-associated apoptosis allows transformation of p53
      deficient cells.
AB  - p53-deficient mouse embryonic fibroblasts were used to establish a direct
      mechanism of tumor suppression by p53 involving the destruction of oncogene
      expressing cells by apoptosis. The absence of p53 enhanced cell growth, appeared
      sufficient for immortalization, and allowed a single oncogene [adenovirus early
      region 1A (E1A)] to transform cells to a tumorigenic state. p53 suppressed
      transformation of E1A-expressing cells by apoptosis. Apoptosis was associated
      with p53 stabilization and was triggered by environmental signals that normally
      suppress cell growth. Absence of even a single p53 allele significantly enhanced
      cell growth and survival. Although abrogation of apoptosis allowed transformation
      by E1A alone, escape from apoptosis susceptibility was not a prerequisite for
      tumor growth. Consequently, p53 mutation could enhance the survival of malignant
      cells expressing oncogenes activated early in tumor progression.

PMID- 8134346
TI  - Vasoactive intestinal peptide increases intracellular calcium in astroglia:
      synergism with alpha-adrenergic receptors.
AB  - In type I astrocytes from rat cerebral cortex, vasoactive intestinal peptide
      (VIP) at concentrations below 1 nM evoked an increase in intracellular calcium
      ion concentration. This response, however, was observed in only 18% of the
      astrocytes examined. alpha-Adrenergic stimulation with phenylephrine or
      norepinephrine also resulted in an intracellular calcium response in these cells
      and the threshold sensitivity of astrocytes to phenylephrine was vastly different
      from cell to cell. Treatment of these astrocytes with VIP (0.1 nM) together with
      phenylephrine at subthreshold concentrations produced large increases in
      intracellular Ca2+ concentration ([Ca2+]i) and oscillations. The continued
      occupation of the alpha-adrenergic receptor was required for sustained synergism.
      Both alpha-receptor stimulation and stimulation with the mixture of agonists
      induced the cellular calcium response by triggering release of calcium from
      cellular stores, since the response persisted in the absence of extracellular
      calcium. Furthermore, thapsigargin pretreatment, which depletes intracellular
      stores, abolished the agonist-induced [Ca2+]i response. VIP (0.1 nM) and
      phenylephrine were found to increase cellular levels of inositol phosphates;
      however, there was no apparent additivity in this response when the agonists were
      added together. These observations suggest a calcium-mediated second messenger
      system for the high-affinity VIP receptor in astrocytes and that alpha-adrenergic
      receptors act synergistically with the VIP receptor to augment an intracellular
      calcium signal. The synergism between diverse receptor types may constitute an
      important mode of cellular signaling in astroglia.

PMID- 8134347
TI  - Delayed emergence of effects of memory-enhancing drugs: implications for the
      dynamics of long-term memory.
AB  - Many theories of memory postulate that processing of information outlasts the
      learning situation and involves several different physiological substrates. If
      such physiologically distinct mechanisms or stages of memory do in fact exist,
      they should be differentially affected by particular experimental manipulations.
      Accordingly, a selective improvement of the processes underlying short-term
      memory should be detectable only while the information is encoded in the short
      term mode, and a selective influence on long-term memory should be detectable
      only from the moment when memory is based on the long-term trace. Our comparative
      study of the time course of the effects of the cholinergic agonist arecoline, the
      gamma-aminobutyric acid type B receptor antagonist CGP 36742, the angiotensin
      converting enzyme inhibitor captopril, and the nootropic oxiracetam, four
      substances with completely different primary sites of action, show that the
      memory-enhancing effects consistently come into evidence no sooner than 16-24 h
      after the learning trial. On the one hand, this finding suggests that all these
      substances act by way of the same type of mechanism; on the other hand, it
      demonstrates that the substrate modulated by the compounds forms the basis of
      memory only after 16-24 h. From the observation that animals also show clear
      signs of retention during the first 16 h--i.e., before the effects of the
      substances are measurable--it can be inferred that retention during this time is
      mediated by other mechanisms that are not influenced by any of the substances.

PMID- 8134348
TI  - An3 mRNA encodes an RNA helicase that colocalizes with nucleoli in Xenopus
      oocytes in a stage-specific manner.
AB  - An3 is a maternal mRNA localized to the animal hemisphere of oocytes and early
      embryos. We have analyzed the enzymatic activity and the subcellular localization
      of the protein encoded by An3 mRNA during Xenopus oogenesis. Antibodies raised
      using recombinant full-length and truncated An3 protein recognized a single
      protein in Xenopus and single proteins from HeLa cells, Drosophila, mouse testes,
      and Saccharomyces cerevisiae. An3 protein immunoprecipitated from stage IV and
      stage VI oocytes had ATP-dependent RNA helicase activity. The subcellular
      location of An3 protein changed during oocyte development. In previtellogenic
      oocytes, An3 was present throughout the nucleus; cytoplasmic localization was
      relatively sparse. Nuclear localization in mid-vitellogenic oocytes was primarily
      nucleolar; cytoplasmic staining increased relative to earlier stages. In stage VI
      oocytes, An3 protein was detected only in the cytoplasm. The temporal change in
      An3 protein localization is consistent with a role in the production of large
      maternal pools of rRNA during oogenesis.

PMID- 8134345
TI  - Mutations in PRG1, a yeast proteasome-related gene, cause defects in nuclear
      division and are suppressed by deletion of a mitotic cyclin gene.
AB  - Proteasomes are ubiquitous complexes exhibiting proteolytic activity in vitro.
      The function(s) of these enzymes in vivo is not known. To investigate the in vivo
      role of proteasomes, four temperature-sensitive alleles of the Saccharomyces
      cerevisiae proteasome-related gene, PRG1, were constructed and analyzed. At both
      the permissive and restrictive temperatures, many prg1 cells have a large bud,
      contain replicated DNA, and have their nucleus positioned at the neck with a
      short spindle. These different phenotypes indicate a defect in nuclear division.
      Consistent with a nuclear division defect, prg1 mutant strains lose a dispensable
      chromosome at a higher frequency than wild-type cells. Importantly, deletion of
      CLB2, a gene encoding a mitotic cyclin, suppresses the temperature-sensitive
      growth phenotype of prg1 mutant strains. Our results indicate that proteasomes
      are important for nuclear division and suggest that they participate in
      degradation of the Clb2 protein (Clb2p).

PMID- 8134349
TI  - A gene encoding a DnaK/hsp70 homolog in Escherichia coli.
AB  - Eukaryotic organisms have been shown to have multiple forms of hsp70-class stress
      related proteins, but only a single family member, DnaK, has been found in
      prokaryotes. We report here the identification of a heat shock cognate gene,
      designated hsc, in Escherichia coli. The amino acid sequence deduced from hsc
      predicts a 65,647-Da polypeptide having 41% sequence identity with DnaK from E.
      coli, and overexpression produces a protein (Hsc66) with properties similar to
      DnaK. In contrast to dnaK, however, the hsc gene lacks a consensus heat shock
      promoter sequence, and expression is not induced by elevated temperature. The hsc
      gene is located near 54 min on the physical map, immediately upstream of the fdx
      gene, which encodes a [2Fe-2S] ferredoxin; evidence is presented that the hsc and
      fdx genes make up a bicistronic operon in which expression of the ferredoxin is
      coupled to that of Hsc66. The function of Hsc66 is not known, but the
      coregulation of its expression with that of ferredoxin suggests the possibility
      of a specific role in association with the ferredoxin protein.

PMID- 8134350
TI  - Structure of the gene V protein of bacteriophage f1 determined by multiwavelength
      x-ray diffraction on the selenomethionyl protein.
AB  - The crystal structure of the dimeric gene V protein of bacteriophage f1 was
      determined using multiwavelength anomalous diffraction on the selenomethionine
      containing wild-type and isoleucine-47-->methionine mutant proteins with x-ray
      diffraction data phased to 2.5 A resolution. The structure of the wild-type
      protein has been refined to an R factor of 19.2% using native data to 1.8 A
      resolution. The structure of the gene V protein was used to obtain a model for
      the protein portion of the gene V protein-single-stranded DNA complex.

PMID- 8134352
TI  - Noninvasive measurement of microvascular and interstitial oxygen profiles in a
      human tumor in SCID mice.
AB  - Simultaneous measurements of intravascular and interstitial oxygen partial
      pressure (PO2) in any tissue have not previously been reported, despite the
      importance of oxygen in health and in disease. This is due to the limitations of
      current techniques, both invasive and noninvasive. We have optically measured
      microscopic profiles of PO2 with high spatial resolution in subcutaneous tissue
      and transplanted tumors in mice by combining an oxygen-dependent phosphorescence
      quenching method and a transparent tissue preparation. The strengths of our
      approach include the ability to follow PO2 in the same location for several weeks
      and to relate these measurements to local blood flow and vascular architecture.
      Our results show that (i) PO2 values in blood vessels in well-vascularized
      regions of a human colon adenocarcinoma xenograft are comparable to those in
      surrounding arterioles and venules, (ii) carbogen (95% O2/5% CO2) breathing
      increases microvascular PO2 in tumors, and (iii) in unanesthetized and
      anesthetized mice PO2 drops to hypoxic values at < 200 microns from isolated
      vessels but drops by < 5 mmHg (1 mmHg = 133 Pa) in highly vascularized tumor
      regions. Our method should permit noninvasive evaluations of oxygen-modifying
      agents and offer further mechanistic information about tumor pathophysiology in
      tissue preparations where the surface of the tissue can be observed.

PMID- 8134351
TI  - Convection-enhanced delivery of macromolecules in the brain.
AB  - For many compounds (neurotrophic factors, antibodies, growth factors, genetic
      vectors, enzymes) slow diffusion in the brain severely limits drug distribution
      and effect after direct drug administration into brain parenchyma. We
      investigated convection as a means to enhance the distribution of the large and
      small molecules 111In-labeled transferrin (111In-Tf; M(r), 80,000) and
      [14C]sucrose (M(r), 359) over centimeter distances by maintaining a pressure
      gradient during interstitial infusion into white matter to generate bulk flow
      through the brain interstitium. The volume of distribution (Vd) containing > or =
      1% concentration of infusion solution increased linearly with the infusion volume
      (Vi) for 111In-Tf(Vd/Vi, 6:1) and [14C]sucrose (Vd/Vi, 13:1). Twenty-four hours
      after infusion, the distribution of 111In-Tf was increased and more homogeneous,
      and penetration into gray matter had occurred. By using convection to supplement
      simple diffusion, enhanced distribution of large and small molecules can be
      obtained in the brain while achieving drug concentrations orders of magnitude
      greater than systemic levels.

PMID- 8134354
TI  - Identification of Mycobacterium tuberculosis DNA in a pre-Columbian Peruvian
      mummy.
AB  - The existence of tuberculosis in the pre-Columbian Americas is controversial
      because the morphology of the lesion is not specific, the organism is culturally
      nonviable in ancient tissues, and nonpathogenic soil mycobacteria can contaminate
      buried bodies. We report the recovery of DNA unique to Mycobacterium tuberculosis
      from a lung lesion of a spontaneously mummified, 1000-year-old adult female body
      in southern Peru. This provides the most specific evidence possible for the pre
      Columbian presence of human tuberculosis in the New World.

PMID- 8134353
TI  - Stimulation with specific antigen can block superantigen-mediated deletion of T
      cells in vivo.
AB  - The T-cell response to pigeon cytochrome c peptide, residues 88-104 (pcytC), in
      B10.BR mice is mediated largely by cells bearing both V beta 3 and V alpha 11
      variable regions of the T-cell antigen receptor. These cells are, therefore,
      reactive with the superantigen staphylococcal enterotoxin A (SEA). Recent reports
      have shown that in vivo exposure to superantigen can lead to deletion of
      superantigen-reactive T cells from the pool of mature T cells in the periphery.
      Here we show that upon cotreatment of animals with both SEA and pcytC, bulk
      deletion of the population of SEA-reactive cells is maintained, while the
      subpopulation of SEA-reactive T cells that also responds to pcytC is not deleted
      but instead proliferates in response to pcytC. These results are discussed with
      regard to mechanisms regulating the balance between T-cell tolerance and T-cell
      activation in vivo.

PMID- 8134355
TI  - Molecular analysis of cell surface beta-1,4-galactosyltransferase function during
      cell migration.
AB  - Despite the identification and characterization of cell surface receptors for the
      extracellular matrix, it is unknown how their relative expression and
      cytoskeletal association regulate cell migration. Previous studies have
      identified beta-1,4-galactosyltransferase (GalTase; EC 2.4.1.38) on the surface
      of migrating cells, where it mediates cell migration on basal lamina matrices by
      associating with the cytoskeleton and binding to N-linked oligosaccharides in the
      E8 domain of laminin. In this study, the function of GalTase during cell
      migration was examined directly by analyzing the migration rate of stably
      transfected cell lines in which the relative level of surface GalTase and its
      ability to associate with the cytoskeleton were altered. We show here that the
      cytoskeleton contains a limiting, saturable, number of binding sites for surface
      GalTase. Furthermore, the rate of cell migration was inversely related to the
      ability of surface GalTase to associate with the cytoskeleton. Elevating surface
      GalTase in excess of the number of cytoskeleton-binding sites reduced the rate of
      cell migration, whereas decreasing the amount of surface GalTase available to
      bind the cytoskeleton increased migration rates. These results show that the rate
      of cell migration on basal lamina is directly dependent upon the expression of
      surface GalTase and the ability of this protein to associate with a limiting
      number of cytoskeleton-binding sites.

PMID- 8134356
TI  - Cytoplasmic dynein is involved in nuclear migration in Aspergillus nidulans.
AB  - Nuclear migration plays an important role in the growth and development of many
      organisms including the multinuclear fungus Aspergillus nidulans. We have
      identified four genes, nudA, nudC, nudF, and nudG, in which temperature-sensitive
      mutations affect nuclear distribution. In this report, we describe the cloning of
      the nudA gene by complementation of the mutant phenotype by using a chromosome
      VIII-specific cosmid library. A genomic fragment of nudA hybridized to an mRNA of
      approximately 14 kb. Sequencing analysis of nudA revealed four ATP-binding sites
      that are characteristic of the cytoplasmic dynein heavy chain. The amino acid
      sequence of the nudA gene product shows 52% overall identity with the rat brain
      cytoplasmic dynein heavy chain. Our study provides in vivo evidence that dynein,
      a microtubule motor molecule, plays a role in the nuclear migration process.

PMID- 8134357
TI  - Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger
      and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin.
AB  - Calcitonin (CT), which regulates serum calcium through its actions in bone and
      the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption
      in the proximal kidney tubule is mostly dependent on the activity of the Na,K
      ATPase and the apical Na/H exchanger. We have previously shown that CT regulates
      the activity of the Na,K-ATPase in the proximal kidney tubule cell line LLC-PK1
      in a cell cycle-dependent manner. We report here that, in the same cells, CT also
      regulates the Na/H exchanger through a cell cycle-specific activation of the
      Ca/calmodulin-dependent protein kinase II. In G2 phase, no changes in
      ethylisopropyl amiloride-sensitive 22Na uptake is observed, despite an increase
      in cAMP. In contrast, the hormone inhibits the apical exchanger when the cells
      are in S phase, resulting in an 80% inhibition of 22Na uptake. These results
      demonstrate that CT affects the activity of the two major proximal tubule Na
      transport systems and may help clarify the mechanisms by which CT regulates Na+
      reabsorption.

PMID- 8134358
TI  - RNA polymerase binding using a strongly acidic hydrophobic-repeat region of sigma
      54.
AB  - sigma 54 is a rare bacterial protein that substitutes for sigma 70 in the case of
      Escherichia coli genes transcribed by certain activators with enhancer protein
      like properties. It contains a strongly acidic region of previously unknown
      function. Gel mobility-shift assays using sigma 54 deletion mutants show that
      this region is essential for sigma 54 to bind the core RNA polymerase and recruit
      it to the promoter. Multiple-point mutational analysis shows that the acidic
      amino acids and overlapping periodic hydrophobic amino acids are necessary for
      this binding. Related sequences are not found within the core binding determinant
      of sigma 70, which binds the same core RNA polymerase. This comparison suggests
      that the core RNA polymerase interacts differently with the two sigma factors,
      likely contributing to the critical differences in transcription mechanism in the
      two cases.

PMID- 8134360
TI  - Use of Drosophila mutants to distinguish among volatile general anesthetics.
AB  - The way general anesthetics cause their clinically useful effects on the nervous
      system is not known. Since the principal determinant of the potency of these
      agents is their solubility in oil, the role of chemical structure in affecting
      anesthetic targets has been obscured. In this work, we use an intense beam of
      light (Tinklenberg, J. A., Segal, I. S., Tianzhi, G. & Maze, M. (1991) Ann. N.Y.
      Acad. Sci. 625, 532-539) to assess the effect of general anesthetics on the
      capacity of fruit flies to sense a noxious stimulus and respond to it. By
      examining the effect of halothane-resistant (har) mutations on the potency of
      various volatile anesthetics in this assay, we establish similarities and
      differences between these agents that highlight the was chemical structure
      influences anesthetic action. In general, the potencies of anesthetics with
      different chemical structure are affected to different extents by one or more har
      mutations. However, three anesthetics of related structure (enflurane,
      isoflurane, and desflurane) show quantitatively indistinguishable alterations in
      potency in each of four genetic tests. These results not only identify important
      structural features of anesthetics but also place limits on the classical view
      that all anesthetics act at a common target.

PMID- 8134359
TI  - Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic
      mice.
AB  - The atherogenic macromolecule lipoprotein(a) [Lp(a)] has resisted in vivo
      analyses partly because it is found in a limited number of experimental animals.
      Although transgenic mice expressing human apolipoprotein (a) [apo(a)] have
      previously been described, they failed to assemble Lp(a) particles because of the
      inability of human apo(a) to associate with mouse apolipoprotein B (apoB). We
      isolated a 90-kilobase P1 phagemid containing the human apoB gene and with this
      DNA generated 13 lines of transgenic mice of which 11 expressed human apoB. The
      human apoB transcript was expressed and edited in the liver of the transgenic
      mice. Plasma concentrations of human apoB, as well as low density lipoprotein
      (LDL), were related to transgene copy number; the transgenic line with the most
      copies of human apoB had a > 4-fold increase in LDL cholesterol compared with
      nontransgenics and a lipoprotein profile similar to that of humans. When human
      apoB and apo(a) transgenic mice were bred together, plasma apo(a) in mice
      expressing both human proteins was tightly associated with lipoproteins in the
      LDL density region. These studies demonstrate the successful expression of human
      apoB and the efficient assembly of Lp(a) in mice.

PMID- 8134362
TI  - On Liapunov's convexity theorem.
AB  - A necessary and sufficient condition is given for the range of a finite Rn-valued
      measure to be convex. A related result is given for Banach-valued set functions.

PMID- 8134361
TI  - Mutational analysis of a critical signaling domain of the human interleukin 4
      receptor.
AB  - The human interleukin 4 receptor (hIL-4R) is a member of a superfamily of
      cytokine receptors defined by conserved features of their extracellular domains.
      The intracellular domains of the hIL-4R and of other members of this family lack
      any recognizable enzymatic motifs, though ligand-dependent tyrosine
      phosphorylation of these receptors has been observed. Recent studies have
      suggested that serine-rich and acidic domains within the cytoplasmic portions of
      cytokine receptors might be required for signal transduction. Using deletion and
      truncation mutants of the hIL-4R, we have explored an essential 39-amino acid
      signaling domain that is rich in acidic amino acid residues and in serine
      residues that form consensus phosphorylation sites for known serine/threonine
      kinases. To assess the contribution of these motifs to signaling, we engineered
      site-directed mutants of these residues. Surprisingly, cells expressing mutant
      hIL-4R lacking either the serine or the acidic amino acids retain the ability of
      cells expressing the wild-type receptor to proliferate in hIL-4. Furthermore,
      receptors in which all six cytoplasmic tyrosines are absent can function,
      suggesting that tyrosine phosphorylation of the receptor may be an epiphenomenon
      rather than a requisite event in signaling.

PMID- 8134363
TI  - Folded proteins occur frequently in libraries of random amino acid sequences.
AB  - A library of synthetic genes encoding 80- to 100-residue proteins composed mainly
      of random combinations of glutamine (Q), leucine (L), and arginine (R) has been
      expressed in Escherichia coli. These genes also encode an epitope tag and six
      carboxyl-terminal histidines. Screening of this library by immunoblotting showed
      that 5% of these QLR proteins are expressed at readily detectable levels. Three
      well-expressed QLR proteins were purified and characterized. Each of these
      proteins has significant alpha-helical content, is largely resistant to
      degradation by Pronase, and has a distinct oligomeric structure. In addition, one
      protein unfolds in a highly cooperative manner. These properties of the QLR
      proteins demonstrate that they possess folded structures with some native-like
      properties. The QLR proteins differ from most natural proteins, however, in being
      remarkably resistant to denaturant-induced and thermal-induced unfolding and in
      being relatively insoluble in the absence of denaturants.

PMID- 8134364
TI  - Detection and mapping of amplified DNA sequences in breast cancer by comparative
      genomic hybridization.
AB  - Comparative genomic hybridization was applied to 5 breast cancer cell lines and
      33 primary tumors to discover and map regions of the genome with increased DNA
      sequence copy-number. Two-thirds of primary tumors and almost all cell lines
      showed increased DNA-sequence copy-number affecting a total of 26 chromosomal
      subregions. Most of these loci were distinct from those of currently known
      amplified genes in breast cancer, with sequences originating from 17q22-q24 and
      20q13 showing the highest frequency of amplification. The results indicate that
      these chromosomal regions may contain previously unknown genes whose increased
      expression contributes to breast cancer progression. Chromosomal regions with
      increased copy-number often spanned tens of Mb, suggesting involvement of more
      than one gene in each region.

PMID- 8134365
TI  - Multiple isoforms of CD46 (membrane cofactor protein) serve as receptors for
      measles virus.
AB  - Measles virus (MV) causes a productive infection in humans and certain simian
      hosts. Rodent cells such as Chinese hamster ovary (CHO) and murine cell lines
      normally resist MV infection. Human CD46, or membrane cofactor protein, a
      complement regulatory protein, recently has been reported as the cellular
      receptor for MV. Multiple isoforms of the CD46 protein exist; four of these
      isoforms are commonly expressed on human cells. Expression of each of the four
      isoforms in CHO cells followed by exposure to MV led to the appearance of viral
      proteins within the cells and on the cell surface as detected by
      immunofluorescence. Syncytium formation also was observed in the cultures. CHO
      cells expressing any of the four isoforms and exposed to MV formed infectious
      centers when plated on Vero cell monolayers, indicating that the cells can
      transmit virus to uninfected cells. The murine cell line MC57 expressing the BC1
      isoform of CD46 also stained positively for MV antigens and was positive in the
      infectious center assay after exposure to MV. Treatment of CD46-expressing cells
      with antibody to human CD46 inhibited MV binding in a dose-dependent manner.
      These observations indicate that any of the four primary isoforms of CD46 are
      able to serve as a receptor for MV.

PMID- 8134366
TI  - Redirection of tryptophan leads to production of low indole glucosinolate canola.
AB  - Cruciferous plants are known to produce over a hundred different mustard oil
      glycosides, which are derived from methionine, phenylalanine, or tryptophan. In
      oil-producing crops like Brassica napus (canola), the presence of indole
      glucosinolates in seed protein meals has decreased meal palatability and has
      limited their value as animal feed. We have transformed canola plants with a gene
      that encodes tryptophan decarboxylase (TDC) in an attempt to redirect tryptophan
      into tryptamine rather than into indole glucosinolates. Transgenic plants that
      expressed this decarboxylase activity accumulated tryptamine while
      correspondingly lower levels of tryptophan-derived indole glucosinolates were
      produced in all plant parts compared with nontransformed controls. Of particular
      significance, the indole glucosinolate content of mature seeds from transgenic
      plants was only 3% of that found in nontransformed seeds. These results
      demonstrate how the creation of artificial metabolic sinks could divert
      metabolite flow and be used to remove these undesirable indole glucosinolates,
      thereby increasing the value of the oilseed meals, which are produced after
      extraction of oil from the seed.

PMID- 8134367
TI  - Endosomal aspartic proteinases are required for invariant-chain processing.
AB  - Immunogenic peptides are displayed in the context of class II histocompatibility
      proteins on the surface of antigen-presenting cells. Class II alpha and beta
      subunits bind the invariant chain (I-chain), a transmembrane glycoprotein which
      must dissociate prior to peptide presentation. Proteolytic release of I-chain in
      an acidic compartment is followed by class II alpha beta surface expression. Two
      distinct proteinases sequentially catalyze I-chain dissociation in B
      lymphoblastoid cell lines. An aspartic proteinase initiates processing whereas a
      cysteine proteinase catalyzes the final stages of I-chain release. Inactivation
      of these enzymes prevents class II alpha beta maturation, demonstrating that
      acidic proteinases are essential for the generation of functional class II
      complexes. I-chain processing was localized to a dense endosomal compartment,
      suggesting this is the first site where class II alpha beta become accessible to
      peptides. I-chain fragments complexed with class II alpha beta accumulate in
      dense endosomes of B-lymphoblastoid cells treated with cysteine proteinase
      inhibitors. A signal for endosomal retention/targeting present in the cytoplasmic
      tail of these fragments may sequester class II alpha beta in this compartment
      until I-chain processing is complete.

PMID- 8134368
TI  - Nuclear concentration and mitotic dispersion of the essential cell cycle protein,
      p13suc1, examined in living cells.
AB  - Stamen hair cells of Tradescantia virginiana have been microinjected with p13suc1
      labeled with carboxyfluorescein (CF) and studied throughout the division cycle in
      living cells by using the confocal laser scanning microscope. The protein,
      p13suc1, is essential for the rapid inactivation of the key mitotic catalyst,
      p34cdc2 kinase, at anaphase and for completion of nuclear division. During
      interphase or prophase, CF-p13suc1 concentrates quickly (< 2 min) in nuclei,
      reaching levels that are approximately 2-fold greater than those in the
      cytoplasm. At nuclear envelope breakdown, CF-p13suc1 permeates throughout the
      entire spindle and nonspindle cytoplasm. The protein is excluded from the tightly
      condensed chromosomes but otherwise no regions accumulate or exclude the protein.
      It remains evenly distributed throughout metaphase, anaphase, and well into
      cytokinesis; however, during telophase CF-p13suc1 reconcentrates in the daughter
      nuclei.

PMID- 8134369
TI  - Dominant negative inhibition of tumorigenesis in vivo by human insulin-like
      growth factor I receptor mutant.
AB  - Although insulin-like growth factor I (IGF-I) is a mitogenic growth factor, its
      role in tumorigenesis is unclear. We therefore transfected wild-type and
      truncated beta-subunit mutant (952STOP) human IGF-I receptor cDNAs into Rat-1
      fibroblasts. Rat-1 transfectants expressed 2.5- to 7-fold increased IGF-I
      receptor mass, while the Kd for IGF-I binding was unchanged. The Rat-1 cells
      transfected with wild-type receptor cDNA responded to in vitro IGF-I treatment by
      increased proliferation and DNA synthesis. Cells overexpressing wild-type
      receptors were also transformed as evidenced by ligand-dependent colony
      proliferation in soft agar. After injection into athymic nude mice, all wild-type
      transfectants formed solid sarcomas within 3 weeks, and ex vivo tumor cell assays
      confirmed continued overexpression of human IGF-I receptors. In contrast, both
      DNA synthesis and proliferation of 952STOP-transfected cells were attenuated
      below that of untransfected cells. 952STOP cells were nonresponsive to IGF-I in
      vitro and were unable to sustain anchorage-independent growth. No tumors were
      induced for up to 8 weeks after injection of 952STOP transfectants into athymic
      mice, despite the presence of demonstrable endogenous IGF-I receptors on the
      952STOP-transfected cells. Therefore, 952STOP behaves as a dominant negative
      inhibitor of endogenous IGF-I receptor function, probably by assembling
      nonfunctional hybrid rat/mutant human receptor tetramers.

PMID- 8134370
TI  - Suppression of calcium-dependent membrane currents in human fibroblasts by
      replicative senescence and forced expression of a gene sequence encoding a
      putative calcium-binding protein.
AB  - Human diploid fibroblasts (HDFs) possess Ca(2+)-dependent membrane currents.
      These currents were suppressed in late-passage normal (senescent) HDFs and
      prematurely senescent HDFs derived from a subject with Werner syndrome (WS),
      compared with early-passage normal (young) HDFs. When young HDFs were
      microinjected with mRNA transcribed in vitro from a cDNA (WS3-10) which encodes a
      protein bearing a putative Ca(2+)-binding site and whose endogenous gene is
      overexpressed in senescent and WS HDFs, membrane currents fell to levels present
      in senescent and WS HDFs. Thus, both replicative senescence and forced expression
      of the WS3-10 gene sequence lead to suppression of Ca(2+)-dependent membrane
      currents, which suggests that a causal connection exists between these two
      processes.

PMID- 8134371
TI  - Role of an Escherichia coli stress-response operon in stationary-phase survival.
AB  - The phage shock protein operon (pspABCE) of Escherichia coli is strongly
      expressed in response to stressful environmental conditions, such as heat shock,
      ethanol treatment, osmotic shock, and filamentous phage infection. We show that
      bacteria lacking the pspABC genes exhibit a substantial decrease in the ability
      to survive prolonged incubation in stationary phase under alkaline conditions (pH
      9). The psp mutant bacteria grow approximately as well as wild-type strains in
      the alkaline medium, and stationary-phase survival of the psp mutants improves
      substantially at pH values closer to the optimal growth range (pH 6-8). In late
      stationary-phase (1- to 2-day-old) cells, the operon can be strongly induced
      under certain conditions, and PspA can become one of the most highly expressed
      bacterial proteins. The combination of stationary-phase starvation and alkaline
      pH is likely to place a severe strain on the maintenance of endogenous energy
      sources, and, consistent with these effects, we find that psp expression is also
      induced by uncouplers of oxidative phosphorylation and other agents that
      interfere with energy production. The death rate of psp mutants in stationary
      phase is accelerated by the presence of wild-type bacteria in the same culture,
      suggesting that the psp operon may play a significant role in enabling E. coli to
      compete for survival under nutrient- or energy-limited conditions.

PMID- 8134372
TI  - Perception of Rhizobium nodulation factors by tomato cells and inactivation by
      root chitinases.
AB  - The bacterial genera Rhizobium and Bradyrhizobium, nitrogen-fixing symbionts of
      legumes, secrete specific lipo-chitooligosaccharides that induce the formation of
      nodules on their host plants. When preparations of such nodulation-inducing
      factors (Nod factors) were added to suspension-cultured tomato cells, a rapid and
      transient alkalinization of the culture medium occurred. Lipo-oligosaccharide
      preparations from Rhizobium or Bradyrhizobium treated with flavonoids, known
      inducers of Nod factor synthesis, were up to 100 times more potent in inducing
      alkalinization than the ones from untreated bacteria. The activity was absent
      from preparations of the mutant strain Rhizobium sp. NGR234 delta nodABC, unable
      to produce any Nod factors. Preparations of Nod factors from various bacteria as
      well as individual, highly purified Nod factors from Rhizobium sp. NGR(pA28)
      induced alkalinization in the tomato cell cultures at nanomolar concentrations.
      This demonstrates that Nod factors can be perceived by tomato, a nonhost of
      rhizobia. Using the alkalinization response as a sensitive bioassay, Nod factors
      were found to be inactivated by plant chitinases. Root chitinases purified from
      different legumes differed in their potential to inactivate differently
      substituted Nod factors produced by Rhizobium sp. NGR(pA28). This indicates that
      the specificity of the bacterium-host plant interaction may be due, at least in
      part, to differential inactivation of Nod factors by root chitinases.

PMID- 8134373
TI  - Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl
      cotransporter.
AB  - By mediating the coupled movement of Na, K, and Cl ions across the plasma
      membrane of most animal cells, the bumetanide-sensitive Na-K-Cl cotransporter
      (NKCC) plays a vital role in the regulation of ionic balance and cell volume. The
      transporter is a central element in the process of vectorial salt transport in
      secretory and absorptive epithelia. A cDNA encoding a Na-K-Cl cotransport protein
      was isolated from a shark rectal gland library by screening with monoclonal
      antibodies to the native shark cotransporter. The 1191-residue protein predicted
      from the cDNA sequence has 12 putative transmembrane domains flanked by large
      cytoplasmic N and C termini. Regulatory phosphoacceptor residues in isolated
      peptides are identified as Thr-189 and Thr-1114 in the predicted sequence.
      Northern blot analysis identified a 7.4-kb mRNA in rectal gland and most other
      shark tissues; a 5.2-kb mRNA was restricted to shark kidney. Homology with an
      uncharacterized gene from Caenorhabditis elegans and with the thiazide-sensitive
      Na-Cl cotransporter of flounder urinary bladder was found over most of the coding
      region; shorter stretches of homology were found with a C. elegans cDNA and with
      an uncharacterized gene of cyanobacterium. Human HEK-293 cells have been stably
      transfected with the shark cDNA and shown to express Na-K-Cl cotransport activity
      with the bumetanide sensitivity of the shark protein. The expressed transporter
      is functionally quiescent in the host cells and can be activated by depleting the
      cells of chloride.

PMID- 8134374
TI  - Solution structure of a trefoil-motif-containing cell growth factor, porcine
      spasmolytic protein.
AB  - The porcine spasmolytic protein (pSP) is a 106-residue cell growth factor that
      typifies a family of eukaryotic proteins that contain at least one copy of an
      approximately 40-amino acid protein domain known as the trefoil motif. In fact,
      pSP contains two highly homologous trefoil domains. We have determined the
      complete three-dimensional solution structure of pSP by using a combination of
      two- and three-dimensional 1H NMR spectroscopy and distance geometry
      calculations. pSP is a relatively elongated molecule, consisting of two compact
      globular domains joined via a small interface. The protein's two trefoil domains
      adopt the same tertiary structure and contain a core C-terminal two-stranded
      antiparallel beta-sheet, preceded by a 6-residue helix that packs against the N
      terminal beta-strand. The remainder of the protein backbone is taken up by two
      short loops that lie on either side of the beta-hairpin and are linked by an
      extended region that wraps around the C-terminal beta-strand. The topology of the
      protein backbone observed for the trefoil domains in pSP represents an unusual
      polypeptide fold. A striking feature of both trefoil domains is a surface patch
      formed from five conserved residues that have no obvious structural role. The two
      patches are located at the far ends of the protein molecule, and we propose that
      these residues form at least part of the receptor binding site, or sites, on pSP.

PMID- 8134375
TI  - Molecular cloning, characterization, and overexpression of ERG7, the
      Saccharomyces cerevisiae gene encoding lanosterol synthase.
AB  - We report the cloning, characterization, and overexpression of Saccharomyces
      cerevisiae ERG7, which encodes lanosterol synthase [(S)-2,3-epoxysqualene mutase
      (cyclizing, lanosterol forming), EC 5.4.99.7], the enzyme responsible for the
      complex cyclization/rearrangement step in sterol biosynthesis. Oligonucleotide
      primers were designed corresponding to protein sequences conserved between
      Candida albicans ERG7 and the related Arabidopsis thaliana cycloartenol synthase
      [(S)-2,3-epoxysqualene mutase (cyclizing, cycloartenol forming), EC 5.4.99.8]. A
      PCR product was amplified from yeast genomic DNA using these primers and was used
      to probe yeast libraries by hybridization. Partial-length clones homologous to
      the two known epoxysqualene mutases were isolated, but a full-length sequence was
      found neither in cDNA nor genomic libraries, whether in phage or plasmids. Two
      overlapping clones were assembled to make a functional reconstruction of the
      gene, which contains a 2196-bp open reading frame capable of encoding an 83-kDa
      protein. The reconstruction complemented the erg7 mutation when driven from
      either its native promoter or the strong ADH1 promoter.

PMID- 8134376
TI  - PCR amplification of up to 35-kb DNA with high fidelity and high yield from
      lambda bacteriophage templates.
AB  - A target length limitation to PCR amplification of DNA has been identified and
      addressed. Concomitantly, the base-pair fidelity, the ability to use PCR products
      as primers, and the maximum yield of target fragment were increased. These
      improvements were achieved by the combination of a high level of an exonuclease
      free, N-terminal deletion mutant of Taq DNA polymerase, Klentaq1, with a very low
      level of a thermostable DNA polymerase exhibiting a 3'-exonuclease activity (Pfu,
      Vent, or Deep Vent). At least 35 kb can be amplified to high yields from 1 ng of
      lambda DNA template.

PMID- 8134377
TI  - Multiple substitutions in the von Willebrand factor gene that mimic the
      pseudogene sequence.
AB  - We have analyzed a type IIB and a type I von Willebrand disease family for the
      presence of mutations in the region coding for the glycoprotein Ib binding domain
      of the von Willebrand factor. Since this sequence is also present in the highly
      homologous von Willebrand factor pseudogene, we have studied genomic DNA as well
      as cDNA, which was produced from RNA isolated from endothelial cells or
      platelets. In both families, we have detected multiple consecutive nucleotide
      substitutions in the 5' end of exon 28 that result in a sequence identical to the
      von Willebrand factor pseudogene. These substitutions were also found in cDNA,
      which proves that they are present in the active gene. The occurrence of multiple
      adjacent substitutions that exactly reflect a part of the sequence of the von
      Willebrand factor pseudogene is difficult to reconcile with sequential single
      mutational events. We therefore hypothesize that each of these multiple
      substitutions arose from one recombinational event between gene and pseudogene.

PMID- 8134378
TI  - Activation of the interleukin 6 gene by Mycobacterium tuberculosis or
      lipopolysaccharide is mediated by nuclear factors NF-IL6 and NF-kappa B.
AB  - The host response to Mycobacterium tuberculosis includes granuloma formation at
      sites of infection and systemic symptoms. Cytokines have been identified by
      immunohistochemistry in granulomas in animal models of bacillus Calmette-Guerin
      (BCG) infection and are released by mononuclear phagocytes upon stimulation by
      mycobacterial proteins. In this regard, the cytokine interleukin 6 (IL-6) may
      play a role in the clinical manifestations and pathological events of
      tuberculosis infection. We have demonstrated that lipoarabinomannan (LAM) from
      the mycobacterial cell wall, which was virtually devoid of lipopolysaccharide
      (LPS), stimulated mononuclear phagocytes to release IL-6 in a dose-response
      manner. LAM and LPS were potent inducers of IL-6 gene expression in peripheral
      blood monocytes. Both LAM- and LPS-inducible IL-6 promoter activity was localized
      to a DNA fragment, positions -158 to -49, by deletion analysis and
      chloramphenicol acetyltransferase assay. Two nuclear factor NF-IL6 (positions 
      153 to -145 and -83 to -75) and one nuclear factor NF-kappa B (positions -72 to 
      63) motifs are present within this fragment. Site-directed mutagenesis of one or
      more of these motifs within the IL-6 promoter demonstrated that each has positive
      regulatory activity and that they could act in a function- and orientation
      independent manner. Deletion of all three elements abolished inducibility of IL-6
      promoter activity by both LAM and LPS. We conclude that the NF-IL6 and NF-kappa B
      sites mediate IL-6 induction in response to both LPS and LAM, acting as bacterial
      or mycobacterial response elements.

PMID- 8134379
TI  - Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding,
      transcriptional activity, and association with transcription factor ERCC3.
AB  - Chronic active hepatitis caused by infection with hepatitis B virus, a DNA virus,
      is a major risk factor for human hepatocellular carcinoma. Since the oncogenicity
      of several DNA viruses is dependent on the interaction of their viral
      oncoproteins with cellular tumor-suppressor gene products, we investigated the
      interaction between hepatitis B virus X protein (HBX) and human wild-type p53
      protein. HBX complexes with the wild-type p53 protein and inhibits its sequence
      specific DNA binding in vitro. HBX expression also inhibits p53-mediated
      transcriptional activation in vivo and the in vitro association of p53 and ERCC3,
      a general transcription factor involved in nucleotide excision repair. Therefore,
      HBX may affect a wide range of p53 functions and contribute to the molecular
      pathogenesis of human hepatocellular carcinoma.

PMID- 8134380
TI  - Secretion of human hepatitis B virus is inhibited by the imino sugar N
      butyldeoxynojirimycin.
AB  - The imino sugar N-butyldeoxynojirimycin (NBDNJ) is a potent inhibitor of the
      oligosaccharide-trimming enzyme alpha-glucosidase I. Hepatitis B virus (HBV)
      contains three surface proteins (HBs proteins) of different sizes that are singly
      or doubly N-glycosylated and are essential for the formation of infectious virus.
      Therefore, the replication and secretion of HBV in the human hepatoma cell line
      HepG2 were studied in the presence of NBDNJ. In the stably HBV-transfected HepG
      2.2.15 cells and in HBV-infected HepG2 cells, NBDNJ suppressed secretion of HBV
      particles and caused intracellular retention of HBV DNA. The secretion of
      subviral particles was less affected. These data suggest that inhibitors of
      oligosaccharide trimming may be useful for antiviral therapy of hepatitis B and
      for the study of the intracellular transport of the viral glycoproteins.

PMID- 8134381
TI  - Cloning of a 3-methyladenine-DNA glycosylase from Arabidopsis thaliana.
AB  - We have isolated an Arabidopsis thaliana cDNA that complements the methyl
      methanesulfonate-sensitive phenotype of an Escherichia coli double mutant
      deficient in 3-methyladenine glycosylases (DNA-3-methyladenine glycosidases I and
      II, EC 3.2.2.20 and 3.2.2.21, respectively, encoded by tag and alkA). Expression
      of the Arabidopsis cDNA enhances the methyl methanesulfonate resistance of the E.
      coli double mutant by nearly four orders of magnitude. The cDNA corresponds to a
      single-copy, nuclearly encoded sequence which specifies a predicted 28.1-kDa
      protein with a charge of +8 at pH 7.0. Enzymatic analysis of extracts prepared
      from the transformed mutants indicates that the cDNA encodes a 3-methyladenine
      glycosylase. The predicted amino acid sequence of the Arabidopsis glycosylase has
      significant homology to other eukaryotic 3-methyladenine glycosylases.

PMID- 8134382
TI  - Manifold sequencing: efficient processing of large sets of sequencing reactions.
AB  - Automated instruments for DNA sequencing greatly simplify data collection in the
      Sanger sequencing procedure. By contrast, the so-called front-end problems of
      preparing sequencing templates, performing sequencing reactions, and loading
      these on the instruments remain major obstacles to extensive sequencing projects.
      We describe here the use of a manifold support to prepare and perform sequencing
      reactions on large sets of templates in parallel, as well as to load the reaction
      products on a sequencing instrument. In this manner, all reaction steps are
      performed without pipetting the samples. The strategy is applied to sequencing
      PCR-amplified clones of the human mitochondrial D-loop and for detection of
      heterozygous positions in the human major histocompatibility complex class II
      gene HLA-DQB, amplified from genomic DNA samples. This technique will promote
      sequencing in a clinical context and could form the basis of more efficient
      genomic sequencing strategies.

PMID- 8134383
TI  - Developmentally excised sequences in micronuclear DNA of Paramecium.
AB  - DNA processing occurs in ciliates at autogamy and conjugation when new
      macronuclei are formed from micronuclei and old macronuclei degrade. Processing
      of micronuclear DNA consists of removal of certain internal sequences,
      chromosomal fragmentation, addition of new telomeres, and amplification. Aside
      from a recent brief report, internal eliminated sequences have not been described
      in Paramecium. In this paper we characterize nine internal eliminated sequences
      found within and near the gene that codes for surface protein A in Paramecium
      tetraurelia. Of these nine, seven are located within the translated portion of
      the gene, and all include short, inverted terminal repeats. The characteristic
      sequence, TA, appears at the boundaries of all of the internal eliminated
      sequences.

PMID- 8134384
TI  - Temporal phosphorylation of the Drosophila period protein.
AB  - The period gene (per) is required for Drosophila melanogaster to manifest
      circadian (congruent to 24 hr) rhythms. We report here that per protein (PER)
      undergoes daily oscillations in apparent molecular mass as well as abundance. The
      mobility changes are largely or exclusively due to multiple phosphorylation
      events. The temporal profile of the classic short-period form of PER (PERS) is
      altered in a manner consistent with the mutant strain's behavioral phenotype. As
      changes in abundance and phosphorylation persist under constant environmental
      conditions, they reflect or contribute to a free-running rhythm. We suggest that
      the phosphorylation status of PER is an important determinant in the Drosophila
      clock's time-keeping mechanism.

PMID- 8134385
TI  - Cloning and expression of a distinctive class of self-incompatibility (S) gene
      from Papaver rhoeas L.
AB  - We present the identification, cloning, and characterization of a self
      incompatibility (S) gene from Papaver rhoeas that has no significant homology to
      any previously reported gene sequences, including S genes from other species.
      This result suggests that a different self-incompatibility mechanism may be
      operating in this species and has important implications for the evolutionary
      relationships between the S genes. The S1 cDNA was cloned by using an
      oligonucleotide based upon N-terminal amino acid sequence data from stigmatic
      proteins that show complete linkage with the S1 gene. The single-copy gene has
      been expressed in Escherichia coli to test biological activity. Although the
      recombinant S1 protein (S1e) is not processed in the same way as the protein
      produced in the plant, it exhibits, in vitro, the specific pollen inhibitory
      activity expected of an S gene product; pollen carrying the S1 allele is
      inhibited, whereas pollen not carrying S1 is not inhibited. These results provide
      definitive demonstration that the product of a cloned S gene has S-specific
      pollen inhibitory activity.

PMID- 8134386
TI  - Biochemical evidence for a complex involving dihydropyridine receptor and
      ryanodine receptor in triad junctions of skeletal muscle.
AB  - Membrane vesicles enriched in both ryanodine receptor and dihydropyridine
      receptor were obtained from rabbit skeletal muscle and solubilized with 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate. Analysis of the
      sedimentation behavior of the solubilized proteins showed the existence of a
      population of alpha 1 subunits of the dihydropyridine receptor which cosedimented
      with the ryanodine receptor. Solubilized proteins were immunoprecipitated with
      antibodies directed against either the ryanodine receptor or the alpha 1, alpha
      2, or beta subunits of the dihydropyridine receptor. Immunoprecipitated proteins
      were identified by Western blot analysis and by specific labeling with
      [3H]ryanodine or [3H]PN200-110. Immunoprecipitation of the solubilized proteins
      with antibodies directed against the dihydropyridine receptor led to the
      coimmunoprecipitation of the ryanodine receptor. Conversely, immunoprecipitation
      with antibodies directed against the ryanodine receptor led to an immune complex
      containing both receptors, but these antibodies were unable to precipitate
      purified dihydropyridine receptor. These results demonstrate that ryanodine
      receptor and dihydropyridine receptor are present in the triad membrane
      preparation in a complex which may play an important role in excitation
      contraction coupling.

PMID- 8134387
TI  - A nucleotide insertion and frameshift cause analbuminemia in an Italian family.
AB  - In analbuminemia, a very rare inherited syndrome, subjects produce little or no
      albumin (1/100th to 1/1000th normal), presumably because of a mutation in the
      albumin gene; yet, they have only moderate edema and few related symptoms owing
      to a compensatory increase in other plasma proteins. Because of the virtual
      absence of albumin the defect must be identified at the DNA level. In this study
      the mutation causing analbuminemia in an Italian family was investigated by
      analysis of DNA from a mother and her daughter. The mother was homozygous for the
      trait and had a serum albumin value of < 0.01 g/dl (about 1/500th normal); the
      daughter was heterozygous for the trait and had a nearly normal albumin value.
      Molecular cloning and sequence analysis of DNA from both mother and daughter
      showed that the mutation is caused by a nucleotide insertion in exon 8; this
      produces a frameshift leading to a premature stop, seven codons downstream. The
      methods of heteroduplex hybridization and single-strand conformation polymorphism
      were used to compare the DNA of the mother and daughter to the DNA of two
      unrelated analbuminemic individuals (one Italian and one American). This showed
      that all three analbuminemic individuals had different mutations; these also
      differed from the mutation in the only human case previously studied at the DNA
      level, which was a splicing defect affecting the ligation of the exon 6-exon 7
      sequences. Thus, analbuminemia may result from a variety of mutations and is
      genetically heterogeneous.

PMID- 8134388
TI  - Arachidonate is a potent modulator of human heat shock gene transcription.
AB  - Cell and tissue injury activate the inflammatory response through the action(s)
      of arachidonic acid and its metabolites, leading to the expression of acute-phase
      proteins and inflammatory cytokines. At the molecular level, little is known how
      arachidonic acid regulates the inflammatory response. As inflammation is also
      associated with local increase in tissue temperatures, we examined whether
      arachidonic acid was directly involved in the heat shock response. Extracellular
      exposure to arachidonic acid induced heat shock gene transcription in a dose
      dependent manner via acquisition of DNA-binding activity and phosphorylation of
      heat shock factor 1 (HSF1). In addition, exposure of cells to low concentrations
      of arachidonic acid, which by themselves did not induce HSF1 DNA-binding
      activity, reduced the temperature threshold for HSF1 activation from elevated
      temperatures which are not physiologically relevant (> 42 degrees C) to
      temperatures which can be attained during the febrile response (39-40 degrees C).
      These results indicate that elevated heat shock gene expression is a direct
      consequence of an arachidonic acid-mediated cellular response.

PMID- 8134389
TI  - Activation of JAK2 kinase mediated by the interleukin 6 signal transducer gp130.
AB  - The interleukin 6 receptor-associated signal transducer, gp130, is shared by
      receptor complexes for leukemia inhibitory factor, oncostatin M, ciliary
      neurotrophic factor, and interleukin 11. We show here that JAK2 kinase is rapidly
      tyrosine phosphorylated in mouse embryonic stem cells whose pluripotentiality is
      maintained only by gp130-sharing cytokines after stimulation that is known to
      induce gp130 homodimerization. JAK1 is also tyrosine phosphorylated, but to a
      lesser extent, under the same conditions. Comparable results are obtained with
      hemopoietic lineage cells such as myeloid leukemic M1 cells and pro-B-cell line
      derived transfectants expressing gp130, the former of which differentiate into
      macrophages after stimulation of gp130 and the latter of which initiate DNA
      synthesis. gp130-dimerizing stimulus upregulates kinase activity of JAK2 as
      revealed by immunocomplex kinase assay. Deletion or point mutation in the
      membrane-proximal cytoplasmic motifs in gp130 that are conserved in the
      hemopoietic cytokine receptor family results in the loss of tyrosine
      phosphorylation of JAK2, which coincides with the lack of signal transducing
      capability of gp130 mutants.

PMID- 8134390
TI  - Multiple origins of a spider radiation in Hawaii.
AB  - The Hawaiian Islands are renowned for some of the most spectacular species
      radiations in the world. Most of these radiations have been attributed to single
      colonization events, although the evidence supporting monophyletic origins is
      often poorly resolved and/or ambiguous. Without a concrete understanding of the
      origins of species radiations, it is impossible to understand the phylogenetic
      pattern of species proliferation or the spectrum of morphological, ecological,
      and behavioral modifications attributable to a single colonist. In this study we
      examined the species radiation of the spider genus Tetragnatha in Hawaii. Unlike
      their mainland congeners, the Hawaiian Tetragnatha are extremely diverse in
      morphology, ecology, and behavior. We tested whether this diversity arose from a
      single or multiple colonization events. We coupled morphological (37 characters)
      and molecular (sequence from the 12S ribosomal subunit of mitochondrial DNA)
      approaches to assess the phylogenetic position of the Hawaiian Tetragnatha
      relative to continental congeners and to examine evidence for monophyly. We
      provide evidence that the Hawaiian Tetragnatha emanate from multiple origins. At
      least two independent species radiations, the "spiny-leg" clade and the web
      building species Tetragnatha stelarobusta and Tetragnatha acuta, have arisen from
      one or more founder events. Two additional natural colonizations have resulted in
      the establishment of non-speciose lineages, as represented by Tetragnatha
      hawaiensis and Doryonychus raptor.

PMID- 8134391
TI  - Antagonism of superantigen-stimulated helper T-cell clones and hybridomas by
      altered peptide ligand.
AB  - T-cell activation by an immunogenic peptide can be antagonized by nonstimulatory
      analogs of that peptide. We investigated this T-cell receptor antagonism by using
      staphylococcal enterotoxin superantigen to stimulate hemoglobin-specific helper T
      (Th) cells because its activation pathway may differ from that of conventional
      antigen. Interestingly, superantigen activation of these Th cells was antagonized
      by hemoglobin peptide analogs even though agonist (superantigen) and antagonist
      (analog peptide) bind at different sites on the major histocompatibility complex
      encoded molecule and the T-cell receptor. The antagonism appeared to be a
      fundamental block in T-cell activation, as phosphoinositol generation, cytokine
      production, and proliferation were reduced in Th1 clones, and, similarly,
      proliferative and cytokine responses were inhibited in Th2 cells. Even T-cell
      hybridoma activation (cytokine production and apoptosis) was inhibited by peptide
      antagonists. Furthermore, analog peptides that functioned as partial agonists for
      these Th cells also antagonized superantigen-induced proliferation and thus were
      a subset of the peptide antagonists. In summary, our results demonstrate that
      analogs of immunogenic peptide are potent antagonists for Th cell responses
      induced by superantigen as well as immunogenic peptide.

PMID- 8134392
TI  - Molecular cloning and structure of a pre-B-cell growth-stimulating factor.
AB  - Generation and proliferation of early B-cell progenitors have been known to
      require stromal cell-derived molecules. A stromal cell line, PA6, was found to
      produce a soluble mediator, which was distinct from interleukin 7 (IL-7) and stem
      cell factor and supported the proliferation of a stromal cell-dependent pre-B
      cell clone, DW34. A cDNA clone encoding this DW34 growth-stimulating factor was
      isolated by expression cloning. The nucleotide sequence contained a single
      substantial open reading frame of 267 nucleotides encoding an 89-amino acid
      polypeptide. The amino acid sequence of this cytokine, designated pre-B-cell
      growth-stimulating factor (PBSF), revealed that it is a member of intercrine
      alpha subfamily. Recombinant PBSF stimulated the proliferation of DW34 cells for
      itself and, furthermore, synergistically augmented the growth of DW34 as well as
      bone marrow B-cell progenitors in the presence of IL-7.

PMID- 8134393
TI  - Predictive capability of proportional hazards regression.
AB  - A measure of the predictive capability of a proportional hazards regression is
      derived. The measure is based on the residuals appropriate to proportional
      hazards regression. A population version is presented and can be seen not to
      depend on the censoring mechanism under the provision that any such censoring be
      independent or conditionally independent of the failure mechanism given the
      covariate. For the special case of a Weibull regression model, for which the
      covariate distribution follows binary, uniform, normal, or exponential laws, we
      derive analytic results. These alone give credence to the measure which can be
      seen to reflect strength of regression effect, as quantified by the parameter
      estimate, although on a scale between 0 and 1, independently of the intercept or
      shape parameter of the particular Weibull law and only weakly dependent on the
      covariate distribution. Extensions to partial and multiple measures of predictive
      ability are straightforward. An example is provided.

PMID- 8134394
TI  - Selective nature of phorbol 12-myristate 13-acetate-induced neoplastic
      transformation in NIH 3T3 cells.
AB  - The ability of phorbol 12-myristate 13-acetate (PMA) at 0.02 microgram/ml to
      induce neoplastic transformation in NIH 3T3 cells is highly dependent on the
      culture conditions. Optimal transformation, indicated by the saturation density
      and extent of focus formation in transferred cultures raised under standard
      conditions, was observed when the original cells were grown in 2% calf serum (CS)
      and exposed continually to PMA for at least 4 weeks before transfer into the
      assay. Transformation of stationary cultures in 10% CS occurred later and to a
      lesser degree than in 2% CS. The same cells subjected to thrice-weekly transfer
      in 2% or 10% CS at low cell density so that they were in a constant state of
      exponential growth exhibited no evidence of transformation in response to PMA.
      This strong condition-dependence of PMA-enhanced transformation is indicative of
      a selection process similar to that described for spontaneous transformation. In
      both cases, transformation is promoted by inhibiting multiplication and prevented
      by maximizing multiplication. Therefore, it has the earmarks of an epigenetic
      rather than a mutational process and requires phenotypic rather than genotypic
      variation to supply the states for selection. The concept of "progressive state
      selection," originally proposed to account for spontaneous transformation, can
      also account for PMA-enhanced transformation.

PMID- 8134395
TI  - Polymer-encapsulated cells genetically modified to secrete human nerve growth
      factor promote the survival of axotomized septal cholinergic neurons.
AB  - Effective treatments for neurodegenerative disorders are limited by our inability
      to alter the progression of the diseases. A number of proteins have specific
      neuroprotective activities in vitro; however, the delivery of these factors into
      the central nervous system over the long term at therapeutic levels has been
      difficult to achieve. BHK cells engineered to express and release human nerve
      growth factor were encapsulated in an immunoisolation polymeric device and
      transplanted into both fimbria-fornix-lesioned rat brains and naive controls. In
      the lesioned rat brain, chronic delivery of human nerve growth factor by the
      encapsulated BHK cells provided nearly complete protection of axotomized medial
      septal cholinergic neurons. Human nerve growth factor continued to be released by
      encapsulated cells upon removal from the aspirative site after 3 weeks or from
      normal rat striatum after 3 and 6 months in vivo. Long-term encapsulated cell
      survival was confirmed by histologic analysis. This encapsulated xenogeneic
      system may provide therapeutically effective amounts of a number of neurotrophic
      factors, alone or in combination, to virtually any site within the body.

PMID- 8134396
TI  - 4,5-Dianilinophthalimide: a protein-tyrosine kinase inhibitor with selectivity
      for the epidermal growth factor receptor signal transduction pathway and potent
      in vivo antitumor activity.
AB  - Deregulated signal transduction via the epidermal growth factor receptor (EGF-R)
      family of protein-tyrosine kinase growth factor receptors is associated with
      proliferative diseases. We describe a class of compounds (4,5
      dianilinophthalimides) that inhibit the EGF-R protein-tyrosine kinase in vitro
      with high selectivity. In cells, 4,5-dianilinophthalmide selectively inhibited
      both ligand-induced EGF-R and p185c-erbB2 autophosphorylation and c-fos mRNA
      induction. Antitumor activity could be demonstrated in vivo against xenografts of
      the A431 and SK-OV-3 tumors, which overexpress the EGF-R and p185c-erbB2,
      respectively. In contrast, a platelet-derived growth factor-driven tumor was not
      inhibited by 4,5-dianilinophthalimide, which is compatible with its cellular
      selectivity and hypothesized mechanism of action. No overt cumulative toxicity
      was observed during treatment even though high efficacy was observed, indicating
      a good therapeutic window. 4,5-Dianilinophthalimides may offer therapeutic agents
      for the treatment of hyperproliferative diseases that overexpress EGF-R family
      protein-tyrosine kinases or their ligands.

PMID- 8134397
TI  - A role for histones H2A/H2B in chromatin folding and transcriptional repression.
AB  - Histone octamers or histone H3/H4 tetramers were reconstituted onto either closed
      circular plasmids containing a single Xenopus 5S rRNA gene or a reiterated array
      of Lytechinus 5S rRNA genes. All "reconstitutes" were found to undergo both Na(+)
      dependent and Mg(2+)-dependent compaction. However, in each case, the compaction
      of nucleosomal templates containing H2A/H2B was much more extensive than
      compaction of templates containing only H3/H4 tetramers. Inclusion of 5 mM MgCl2
      in the transcription buffer increased the level of compaction of nucleosomal
      templates and led to a marked inhibition of both transcription initiation and
      elongation by RNA polymerase III. The inhibitory effect of Mg2+ was reduced
      significantly when DNA templates contained only H3/H4 tetramers, consistent with
      their lesser extent of Mg(2+)-dependent compaction. Thus, the removal of histones
      H2A/H2B from nucleosomal arrays enhances gene activity, in part because of
      decreased levels of chromatin folding.

PMID- 8134398
TI  - In vivo hepatic gene therapy: complete albeit transient correction of factor IX
      deficiency in hemophilia B dogs.
AB  - Hemophilia B is a bleeding disorder caused by mutations in the factor IX gene.
      The disorder is X-linked recessive with a prevalence of about 1 in 30,000
      Caucasian males. Factor IX is naturally synthesized in the liver and secreted
      into blood. Here we report the construction of recombinant adenoviral vectors
      containing the canine factor IX cDNA that are capable of transducing hepatocytes
      in mice at high efficiencies in vivo without partial hepatectomy. The recombinant
      viral vector was used to treat hemophilia B dogs by direct vector infusion into
      the portal vasculature of deficient animals. Plasma factor IX concentrations in
      the treated hemophilia B dogs increased from 0 to 300% of the level present in
      normal dogs, resulting in complete amelioration of the disease as demonstrated by
      normal blood coagulation and hemostatic measurements. Although plasma factor IX
      concentration started to decline after a few days, therapeutic levels of factor
      IX persisted for 1-2 months in the treated animals. The results validate the
      principle of in vivo hepatic gene delivery to reconstitute the genetic deficiency
      in a large animal model and suggest that gene therapy is achievable when long
      acting vectors are developed.

PMID- 8134399
TI  - Immunization with purified N1 and N2 influenza virus neuraminidases demonstrates
      cross-reactivity without antigenic competition.
AB  - Based on the absence of serologic cross-reactivity, the neuraminidases (NAs) of
      influenza A viruses are divided into antigenically discrete subtypes, analogous
      to the hemagglutinin (HA) major antigens with which they share the virion
      surface. An innovative approach to influenza vaccination takes advantage of the
      infection-permissive nature of immunization with NA as the minor surface antigen.
      However, evidence that HA dominates immune response when HA and NA are presented
      together in the intact virion prompted investigation of possible competing
      effects during immunization of NA subtype mixtures ultimately required for human
      vaccination. Immunization of BALB/c mice with purified N1- and N2-subtype NAs
      demonstrated no antigenic competition in primary or secondary response. However,
      when homotypic or heterotypic infection followed immunization, cross-reactive
      antibodies between N1 and N2 were found and "reverse antigen competition"
      occurred with initial NA priming suppressing response to HA following infection
      with virus containing homologous NA. These studies of antigen mixtures have
      implications for the use of combined and chimeric vaccines for diseases other
      than influenza.

PMID- 8134401
TI  - Effects of cobalt or nickel on the sympathetically mediated contractile responses
      in rat-isolated vas deferens.
AB  - Subchronic (30 days) exposure of rats to Co(NO3)2 or NiSO4 (20 mg.kg-1) in
      drinking water caused suppression of the isolated vas deferens contractile
      responses to exogenous adenosine 5'-triphosphate (ATP), noradrenaline, and l
      phenylephrine, shifting the concentration-response curves to the relevant agonist
      to the right. Both metals facilitated the alpha 1-adrenoceptor antagonistic
      effects of prazosin, which resulted in increased pA2 values for the drug (9.68 +/
      0.13 in controls vs. 10.15 +/- 0.12 in Co(2+)-treated preparations and 12.60 +/-
      0.67 in Ni(2+)-treated preparations). The inhibitory effect of clonidine on the
      contractions in response to low-frequency electrical field stimulation (EFS) in
      metal-treated preparations was decreased with pD2 values: 10.52 +/- 0.04 in
      controls, 9.56 +/- 0.13 in Co(2+)-treated preparations and 9.92 +/- 0.16 in
      Ni(2+)-treated preparations. The monophasic contractile responses to low
      frequency EFS (0.1 Hz, 1 ms, 80 V) as well as the first phase of the biphasic
      contractions after high-frequency long-lasting EFS (300 pulses, 0.1 ms, 40 V, at
      4, 8 or 20 Hz) were significantly increased in both groups of heavy metal-treated
      preparations. Therefore, subchronic exposure to Co2+ or Ni2+ leads to changes in
      pre- and postjunctional mechanisms underlying the sympathetically mediated
      contractile activity of isolated rat vas deferens.

PMID- 8134400
TI  - Interplay of positive and negative effectors in function of the C-terminal repeat
      domain of RNA polymerase II.
AB  - RNA polymerase II lacking a C-terminal domain (CTD) was active in transcription
      with purified proteins from yeast but failed to support transcription in a yeast
      extract. CTD dependence could be reconstituted in the purified system by addition
      of two fractions from the extract. An inhibitory fraction abolished transcription
      by both wild-type and CTD-less RNA polymerases; a stimulatory fraction restored
      activity of the wild-type polymerase but had a much lesser effect on the CTD-less
      enzyme. Parallel results were obtained with the use of a kinase inhibitor that
      prevents phosphorylation of the CTD by RNA polymerase II initiation factor b. The
      kinase inhibitor abolished transcription by wild-type polymerase in yeast extract
      but had no significant effect in the purified system. The requirement for both
      the CTD and kinase action for transcription in an extract indicates that CTD
      phosphorylation is involved in opposing the negative effector in the extract.
      Factor b must play a role(s) in addition to phosphorylation of the CTD because it
      was still required for transcription with polymerase lacking a CTD in the
      purified system.

PMID- 8134402
TI  - Effect of a platelet-activating factor antagonist, WEB 2086, on inhibition of
      active oxygen generation in human polymorphonuclear leukocytes.
AB  - We investigated the effect of WEB 2086, 3-[4-(2-chlorophenyl)-9-methyl-6H
      thieno[3,2-f][1,2,4]triazolo- [4,3-a][1,4]-diazepin-2-yl]-1-(4-morpholinyl)-1
      propanone, an antagonist of platelet-activating factor, on the generation of
      active oxygen by human polymorphonuclear leukocytes. This agent inhibited the
      production of oxidative metabolites by these cells following stimulation by
      opsonized zymosan and formyl-methionyl-leucyl-phenylalanine in a time-dependent
      fashion. To determine whether it would directly inhibit the production of oxygen
      metabolites by these cells, they were preincubated with WEB 2086 and washed prior
      to stimulation. WEB 2086 was found to directly inhibit the generation of active
      oxygen metabolites by these cells. WEB 2086 may be a scavenger of active oxygen
      metabolites since it rapidly inhibited the production of active oxygen
      metabolites by these cells. It also directly affected the scavenging of active
      oxygen metabolites that were generated by the opsonized zymosan-stimulated human
      polymorphonuclear leukocytes. This action of WEB 2086 was also noted to be
      exerted against hydroxyl radicals and superoxide anions produced biochemically by
      an electron spin resonance spectrometer. It thus follows that WEB 2086 may
      inhibit the generation of active oxygen metabolites by human polymorphonuclear
      leukocytes and directly influence the scavenging of these metabolites.

PMID- 8134403
TI  - Antisense oligonucleotide of c-myc discriminates between zinc- and dexamethasone
      induced synthesis of metallothionein.
AB  - The metallothionein II genes, whose structures are highly conserved throughout
      the animal kingdom, are composed of three exons and two introns. By using
      synthetic oligonucleotides with sequences complementary to the mRNA coding for
      human metallothionein II, we have shown that (a) inhibition of metallothionein
      synthesis causes cells to die from metal toxicity, (b) metallothionein possesses
      an essential gene, and (c) modifications in oligonucleotide structures exhibit
      specificity in inhibiting metallothionein synthesis. Furthermore, we have
      prepared a synthetic antisense oligodeoxyribonucleotide to the mRNA specific for
      human c-myc and tested its potential to regulate metallothionein synthesis in
      Chang liver cells in culture. The results of this study revealed that the c-myc
      antisense oligodeoxyribonucleotide led to greater induction of zinc-promoted but
      not of cadmium- or dexamethasone-induced synthesis of metallothionein. These data
      are interpreted to suggest that c-myc acts as a repressor of at least one of the
      six human metallothionein isoforms and demonstrates a unique mode of regulation
      capable of discriminating between zinc- and dexamethasone-induced synthesis of
      metallothionein.

PMID- 8134404
TI  - The effects of anti-TNF-alpha antibody and dexamethasone on TCDD-induced
      oxidative stress in mice.
AB  - Recent studies have implicated tumor necrosis factor alpha (TNF-alpha) in the
      acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since TNF-alpha
      sensitizes and activates phagocytic cells to agents that induce them to release
      reactive oxygen species, TNF-alpha may act as an amplifying loop in TCDD-induced
      oxidative stress (OS). Therefore, the effects of anti-TNF-alpha antibody (40
      micrograms/mouse) and dexamethasone (2 mg/kg) treatment on TCDD-induced OS as
      measured by DNA single-strand breaks (SSB) in hepatic nuclei, lipid peroxidation
      in hepatic mitochondria and microsomes, and activation of peritoneal lavage cells
      (PLC) in C57BL/6J mice were studied. One day after treatment with 125 micrograms
      TCDD/kg, anti-TNF-alpha resulted in 70, 27, 33 and 21% decreases in DNA-SSB,
      mitochondrial and microsomal lipid peroxidation and PLC activation, respectively,
      relative to TCDD-treated mice. Dexamethasone produced 8, 32, 35 and 9% decreases
      in DNA-SSB, mitochondrial and microsomal lipid peroxidation and PLC activation,
      respectively, in TCDD-treated animals. The combination of anti-TNF-alpha and
      dexamethasone resulted in 67, 55, 61 and 25% decreases in the above parameters of
      OS, respectively. The results suggest that TNF-alpha release may play a role in
      sensitizing and activating phagocytic cells following treatment with TCDD,
      contributing to the overall OS of animals following exposure to TCDD.

PMID- 8134405
TI  - Pharmacological characterization of muscarinic cholinergic receptors in cat pons
      and cortex. Preliminary study.
AB  - Muscarinic receptors (mAChRs) in the pontine reticular formation comprise a
      critical part of the REM sleep-generating system. Although the role of specific
      mAChR subtypes remains unclear, data from in vivo microinjection studies suggest
      that in the pons the M2 subtype is important for REM sleep generation. The
      present study tested the hypothesis that M2 antagonists would show a greater
      binding potency in feline pons than M1 or M3 antagonists. Competition binding
      assays showed 4-DAMP to be more potent than pirenzepine or AF-DX 116 in its
      ability to displace tritiated quinuclidinyl benzilate, and linear regression
      analyses indicated that 4-DAMP and pirenzepine each interacted with more than one
      binding site. These data demonstrate the presence of a mixture of mAChR subtypes
      in the feline pons, and are consistent with the view that REM sleep is mediated
      by more than one mAChR subtype.

PMID- 8134406
TI  - Binding of spironolactone metabolites in vivo to renal mineralocorticoid
      receptors in guinea pigs.
AB  - Spironolactone (SL) is a mineralocorticoid antagonist used clinically to treat
      hypertension and congestive heart failure. Its mechanism of action involves
      competitive binding to aldosterone receptors in the kidneys, resulting in
      diuresis. It is known that the actions of SL are mediated by metabolites of the
      drug, but the active metabolites have not been definitively identified.
      Accordingly, studies were done to determine which metabolites bind to renal
      mineralocorticoid receptors after SL administration to guinea pigs. The major
      metabolite found in the steroid receptor fraction of kidney cytosol was 7 alpha
      thiomethyl-SL (TM). Incubation of kidney cytosol with varying concentrations (0
      100 pmol/l) of aldosterone resulted in the concentration-dependent displacement
      of TM from the steroid receptor fraction. The steroid receptor fraction from
      renal nuclei of SL-treated animals contained approximately equal concentrations
      of TM, 7 alpha-thio-SL (TH), and canrenone (CAN). Incubation of kidney nuclei
      with aldosterone caused a concentration-dependent displacement of all three
      metabolites. The results indicate that TM is the major SL metabolite that
      interacts with cytosolic mineralocorticoid receptors in kidneys, but that TH and
      CAN may contribute to nuclear receptor binding.

PMID- 8134407
TI  - Metoclopramide does not affect renal function and atrial natriuretic peptide
      release in response to acute saline loading in conscious rats.
AB  - It was previously shown in man that metoclopramide (MCP), a dopamine (DA)-2
      receptor blocker, attenuates the natriuresis of water immersion. In the present
      study, we therefore investigated the effects of MCP on renal function and atrial
      natriuretic peptide (ANP) release in conscious rats. Under basal conditions MCP
      did not affect glomerular filtration rate (GFR) (7.4 +/- 1.7 ml/min/kg without
      and 7.8 +/- 0.6 ml/min/kg with MCP), urinary fractional excretion of Na (FENa)
      (0.3 +/- 0.1% without and 0.3 +/- 0.1% with MCP) and K (FEK) (20.6 +/- 1.4%
      without and 28.0 +/- 6.2% with MCP) or plasma ANP (37 +/- 5 pmol/l without and 31
      +/- 6 pmol/l with MCP). During acute saline loading equal to a 10% rise in body
      weight, which significantly (p < 0.05) increased GFR, MCP again had no effects on
      GFR (8.8 +/- 1.8 ml/min/kg with vs. 9.7 +/- 2.5 ml/min/kg without MCP), FENa
      (24.5 +/- 6.9% with vs. 20.4 +/- 5.1% without MCP), FEK (52.5 +/- 6.9% with vs.
      52.5 +/- 9.5% without MCP) and plasma ANP (89 +/- 8 pmol/l with vs. 91 +/- 9
      pmol/l without MCP). These results indicate that DA does not modulate renal
      function or ANP release via DA-2 receptors under basal conditions nor in response
      to acute saline loading in conscious rats.

PMID- 8134408
TI  - In vitro and in vivo chloroquine-potentiating action of Strychnos myrtoides
      alkaloids against chloroquine-resistant strains of Plasmodium malaria.
AB  - Crude alkaloids of Strychnos myrtoides Gilg & Busse, empirically used as an
      adjuvant to chloroquine (CQ) in Malagasy herbal remedies, were practically devoid
      of intrinsic in vitro and in vivo antimalarial activity. However, when combined
      with CQ at a dose level much lower than their IC50 value, they markedly enhanced
      in vitro the effectiveness of the synthetic drug against a CQ-resistant strain of
      Plasmodium falciparum. They also enhanced in vivo CQ activity against a resistant
      strain of Plasmodium yoelii. By counter-current distribution (CCD) separation of
      the crude alkaloid extract, the two major alkaloids strychnobrasiline (1) and
      malagashanine (2), together with four minor alkaloids, were isolated.
      Strychnobrasiline and malagashanine were devoid of both intrinsic antimalarial
      activity and cytotoxicity effect, but exhibited significant CQ-potentiating
      actions. These findings could account for the above-mentioned empirical use of S.
      myrtoides. The present state of research on antimalarial drug from Strychnos
      genus is also discussed.

PMID- 8134409
TI  - Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome.
AB  - Magnolol and honokiol, biphenyl compounds, were isolated as anti-emetic
      principles from the methanolic extract of Magnolia obovata bark. [6]-, [8]-, and
      [10]-shogaols and [6]-, [8]-, and [10]-gingerols were isolated from the
      methanolic extract of Zingiber officinale rhizome as anti-emetic principles. Some
      phenyl-propanoids with allyl side-chains were found to show the same activity.
      They inhibited the emetic action induced by the oral administration of copper
      sulfate pentahydrate to leopard and ranid frogs.

PMID- 8134410
TI  - From ill-defined extracts to the immunomodulatory lectin: will there be a reason
      for oncological application of mistletoe?
AB  - There is an obvious discrepancy between the popularity of mistletoe extracts and
      their classification as a non-conventional treatment modality with unproven
      efficacy in oncology. The commercial preparations suffer from several major
      drawbacks: lack of precise declarations for the molecular characteristics and the
      concentrations of diverse extract constituents; the composition of extracts can
      even be influenced by the different methods of preparation, the time of harvest,
      and the type of host tree; lack of experimentally substantiated instructions for
      the dose of supposedly effective substance(s) and the schedule of applications to
      clinically trigger an undisputably documented antitumoral activity; lack of
      thorough clinical studies according to the generally accepted criteria as the
      measure for responsible recommendations. To provide the indispensable set of data
      for a rational decision, the immunomodulatory galactoside-specific lectin was
      biochemically characterized and its antitumoral/antimetastatic activity was
      documented in three murine tumor model systems, occurring within a narrow dose
      range. Biweekly treatment with s.c. injections of a lectin dose of 1 ng/kg caused
      no notable harmful side-effects in patients, who showed modulation of selected
      immune parameters. In a group of 23 patients with advanced cancer no at least
      partial remission was seen. In principle, enhancement of factors like cytokine
      availability or NK-cell activity is not necessarily linked to therapeutic
      benefit. Factors such as growth promotion of certain tumor cell lines by
      cytokines, occurrence of respective insensitivity in advanced stages or varying
      levels of target sensitivity to cell-mediated cytotoxicity with significant
      interindividual differences deserve attention. Each tumor class has to be
      considered separately for its responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134411
TI  - Analgesic and anti-ulcerogenic effects of a polar extract from leaves of Vernonia
      condensata.
AB  - An aqueous crude extract and a polar fraction derived from this extract were
      prepared from leaves of Vernonia condensata Baker and assessed in standard rodent
      models of algesia and ulcerogenesis. Oral pretreatment with the lyophilized crude
      extract (200 mg/kg) significantly reduced mouse writhing counts caused by the
      i.p. injection of increasing concentrations (0.6-1.2%) of acetic acid (0.1 ml/10
      g). In doses ranging from 50 to 400 mg/kg, the crude extract inhibited dose
      dependently mouse writhing induced by acetic acid (0.6%) (ED50 = 241 mg/kg) and
      also markedly increased the sleeping time induced by thiopental. The polar
      fraction, prepared by washing out the crude extract with chloroform, did not
      alter sleeping time but kept the analgesic activity (ED50 = 154 mg/kg),
      indicating that these effects are indeed dissociated. In contrast, the tail flick
      response in the immersion test was not modified by the crude extract or the polar
      fraction. The relative potency with which polar fraction and non-steroidal anti
      inflammatory drugs inhibited mouse writhing caused by acetic acid in mice was
      indomethacin >> dypirone > polar fraction > aspirin. Furthermore, the combined
      polar fraction/aspirin or polar fraction/indomethacin treatments presented a
      marked synergistic effect, in contrast to what was observed when submaximal doses
      of indomethacin and aspirin were coadministered, suggesting that polar fraction
      and aspirin like drugs may have complementary analgesic actions. Finally, despite
      being able to potentiate the analgesic effect of indomethacin in mouse writhing
      caused by acetic acid, the pretreatment with the polar fraction (200 mg/kg, oral)
      significantly prevented indomethacin-induced ulcers in rats.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8134412
TI  - Euonymoside A: a new cytotoxic cardenolide glycoside from the bark of Euonymus
      sieboldianus.
AB  - A new cytotoxic cardenolide glycoside, euonymoside A (1), was isolated from the
      bark of Euonymus sieboldianus. The structure of 1 was elucidated as
      acovenosigenin A-3-O-beta-D-glucopyranosyl (1-->2)-alpha-L-rhamnopyranoside. The
      IC50 values of 1 against A549 (human lung carcinoma) and SK-OV-3 (human ovary
      adenocarcinoma) were 0.06 and 0.4 micrograms/ml, respectively.

PMID- 8134413
TI  - Cytotoxic and antibacterial labdane-type diterpenes from the aerial parts of
      Cistus incanus subsp. creticus.
AB  - Seven labdane-type diterpenoids were isolated from the leaves of Cistus incanus
      subsp. creticus; their structures were established by spectroscopic means. All
      compounds were tested in vitro for their cytotoxicity against three cell line
      systems: KB, P-388; and NSCLC-N6. Their antibacterial and antifungal activities
      were tested against Staphylococcus aureus, Staphylococcus epidermidis,
      Pseudomonas aeruginosae, Enterobacter cloacae, Escherichia coli, Klebsiella
      pneumonia, Torulopsis glabrata, Saccharomyces cerevisiae, and Candida albicans as
      well.

PMID- 8134414
TI  - In vitro inhibition of cyclooxygenase and 5-lipoxygenase by alkamides from
      Echinacea and Achillea species.
AB  - Polyunsaturated alkamides isolated from Achillea species, Echinacea angustifolia
      DC., Anacyclus pyrethrum (L.) Link, and Aaronsohnia pubescens (Desf.) Bremer &
      Humphries, (Compositae) were shown to possess inhibitory activity in in vitro
      cyclooxygenase (sheep seminal microsomes) and 5-lipoxygenase (porcine leukocytes)
      assays. Activity appeared to depend on the particular structure of the alkamides.

PMID- 8134415
TI  - Antifungal tests in phytochemical investigations: comparison of bioautographic
      methods using phytopathogenic and human pathogenic fungi.
AB  - The detection limits in two bioautographic assays have been determined for a
      series of antifungal compounds, including clinically used antimycotics,
      fungicidal agrochemicals, and various classes of secondary plant metabolites.
      Target organisms were the filamentous fungus Cladosporium cucumerinum and the
      yeast Candida albicans. For clinical agents and agrochemicals, the detection
      limits in the two assays reflected to a certain extent their known spectrum of
      activity. Most of the plant-derived compounds tested showed a positive response
      in both assays, but with detection limits varying by a factor up to tenfold. For
      screening purposes, it is thus advisable to use both tests, as some activities
      would otherwise go undetected. The MIC values of these substances were determined
      in order to verify a possible correlation with the detection limit in the
      bioautographic assays.

PMID- 8134416
TI  - Effects of alpha-hederin, a saponin extracted from Hedera helix, on cells
      cultured in vitro.
AB  - In this work, we have analysed the effects of alpha-hederin, a monodesmosidic
      triterpenoid saponin isolated from Hedera helix, on mouse B16 melanoma cells and
      non-cancer mouse 3T3 fibroblasts cultured in vitro. Our results indicate that, in
      a serum-free medium, alpha-hederin is cytotoxic and inhibits proliferation in
      both cell lines at rather low concentrations (< 5 micrograms/ml) after only 8
      hours of treatment. Its cytotoxicity decreases in the presence of serum in which
      BSA seems to be able to bind the saponin. alpha-Hederin also induces
      vacuolization of the cytoplasm and membrane alterations leading to cell death.

PMID- 8134417
TI  - In vitro antifungal activity of triterpenoid saponins.
AB  - The antifungal activity of triterpenoid saponins, with hederagenin or oleanolic
      acid as aglycone, was investigated in vitro by the agar dilution method.
      Monodesmosidic hederagenin derivatives were shown to exhibit a broad spectrum of
      activity against yeast as well as dermatophyte species. alpha-Hederin was the
      most active compound, and Candida glabrata was the most susceptible strain. The
      structure-activity relationships are discussed.

PMID- 8134418
TI  - Cytotoxic terpenoids and flavonoids from Artemisia annua.
AB  - The cytotoxic activity of nine terpenoids and flavonoids isolated from Artemisia
      annua was tested in vitro on several human tumor cell lines. These compounds are
      artemisinin, deoxyartemisinin, artemisinic acid, arteannuin-B, stigmasterol,
      friedelin, friedelan-3 beta-ol, artemetin, and quercetagetin 6,7,3',4'
      tetramethyl ether. Friedelane-type triterpenoids were isolated for the first time
      from this plant. Artemisinin and quercetagetin 6,7,3',4'-tetramethyl ether showed
      significant cytotoxicity against P-388, A-549, HT-29, MCF-7, and KB tumor cells.

PMID- 8134419
TI  - Anti-inflammatory active polyacetylenes from Bidens campylotheca.
AB  - The n-hexane extract of Bidens campylotheca Schultz Bip. ssp campylotheca
      (Compositae) showed significant in vitro inhibition of cyclooxygenase (CO) and 5
      lipoxygenase (5-LO). Five polyacetylenes, heptadeca-2E,8E,10E,16-tetraene-4,6
      diyne (1), heptadeca-2E,8Z,10E,16-tetraene-4,6-diyne (2), heptadeca-2E,8E,16
      triene-4,6-diyne-10-ol (3), safynol (5) and, as a new compound, safynol-2-O
      isobutyrate (4) could be isolated and their structures elucidated mainly by UV,
      MS, NMR, and COSY-NMR. The isolated compounds exhibited a significant inhibitory
      effect on cyclooxygenase and 5-lipoxygenase.

PMID- 8134420
TI  - Immunoassays for the quantitative determination of colchicine.
AB  - A radioimmunoassay as well as an enzyme immunoassay for the quantitation of fmol
      amounts of the alkaloid colchicine have been developed. The antiserum used for
      both assays was raised against a conjugate of colchicoside-bovine serum albumin.
      The crude serum was satisfactory for the performance of the radioimmunoassay. For
      the enzyme immunoassay, the antibodies had to be isolated and purified by Rivanol
      treatment with subsequent (NH4)2SO4 precipitation. The measuring range extends
      from 0.1 to 100 ng colchicine for the radioimmunoassay and from 0.05 to 350 ng
      for the enzyme immunoassay with detection limits of 125 fmol and 25 fmol,
      respectively. Both immunoassays cross reacted with colchicoside and 3-demethyl
      colchicine up to 80%. The colchicine content in the newly established suspension
      culture of Colchicum variegatum as well as the influence of various culture media
      on the colchicine production of this cell culture were investigated with the
      radioimmunoassay. The enzyme immunoassay was well suited for the quantitation of
      colchicine in HPLC fractions of Gloriosa and Colchicum seed extracts allowing the
      rapid, sensitive, and precise determination of the substance under investigation.
      The preliminary experiments indicate that both colchicine immunoassays can be a
      useful tool for the analysis of colchicine in tissue and cell culture studies,
      for analysis of plant extracts as well as for biosynthetic investigations.

PMID- 8134421
TI  - Antileishmanial activity of a tetralone isolated from Ampelocera edentula, a
      Bolivian plant used as a treatment for cutaneous leishmaniasis.
AB  - The stem bark of Ampelocera edentula Kuhlm. (Ulmaceae) is used by the Chimanes
      Indians from Bolivia for the treatment of cutaneous leishmaniasis caused by the
      protozoan Leishmania braziliensis. A chloroform extract of the stem barks was
      found to be active against extracellular forms of Leishmania ssp. and Trypanosoma
      cruzi at 50 micrograms/ml. Bioassay-guided fractionation of this extract allowed
      us to isolate one active compound. Its structure was elucidated by spectral and
      chemical studies as 4-hydroxy-1-tetralone. BALB/c mice infected with L.
      amazonensis (PH8) or L. venezuelensis were treated one day after the parasitic
      infection with 4-hydroxy-1-tetralone (25 mg/kg/day) or with reference drug,
      Glucantime (56 mg Sbv/kg/day) for 14 days. Lesion development was the criteria
      used to evaluate the disease severity. 4-Hydroxy-1-tetralone was slightly less
      effective than the reference drug against L. amazonensis or L. venezuelensis.
      Single treatment near the site of infection, 14 days after infection with L.
      amazonensis, with 4-hydroxy-1-tetralone (50 mg/kg) was more effective than
      Glucantime (112 mg/kg). This study is, to our knowledge, the first to show the
      activity of a tetralone for the experimental treatment of New World cutaneous
      leishmaniasis.

PMID- 8134422
TI  - A new glycolipid from Byrsonima crassifolia.

PMID- 8134423
TI  - Suppressive effects of metabolites from Alternaria brassicaea on the hepatitis B
      surface antigen.

PMID- 8134424
TI  - Toxicologic studies of dihydro-5,6-dehydrokawain and 5,6-dehydrokawain.

PMID- 8134425
TI  - The natural history of obstetrical brachial plexus palsy.
AB  - Obstetrical brachial plexus palsy remains an unfortunate consequence of difficult
      childbirth. Sixty-six such patients were reviewed. Included were 28 patients (42
      percent) with upper plexus involvement and 38 (58 percent) with total plexopathy.
      The natural history of spontaneous recovery in all of these patients has been
      determined using an appropriate grading mechanism. Sixty-one patients (92
      percent) recovered spontaneously and five patients (8 percent) required primary
      brachial plexus exploration and reconstruction (median age 12 months),
      demonstrating that most patients do well. Additional analysis was undertaken to
      examine ways in which outcome might be predicted. The analysis does not consider
      whether or not the patient was operated upon. Good or poor recovery was
      determined by the spontaneous recovery observed. Discriminant analysis revealed
      that whereas elbow flexion at 3 months correlated well with spontaneous recovery
      at 12 months, when used as a single parameter it incorrectly predicted recovery
      in 12.8 percent of cases. Shoulder abduction was not a significant predictor of
      recovery. Numerous other early parameters correlated well with spontaneous
      recovery. When elbow flexion and elbow, wrist, thumb, and finger extension at 3
      months were combined into a test score, the proportion of patients whose recovery
      was incorrectly predicted was reduced to 5.2 percent.

PMID- 8134426
TI  - Facial sensibility in adolescents born with cleft lip after undergoing repair in
      infancy.
AB  - Values for facial sensibility measured in 68 adolescents born with cleft lip who
      had undergone repair in infancy (39 unilateral cleft patients with a mean age of
      17 years and 29 bilateral cleft patients with a mean age of 19 years) were
      compared to values of 22 noncleft controls (mean age 18 years). Static two-point
      discrimination results and cutaneous pressure thresholds were similar between
      controls and cleft patients. Vibratory threshold values were lower in cleft
      patients, with significant differences (p < 0.05) in the nasolabial and upper lip
      skin areas. These differences might indicate minor sensory abnormalities of the
      quickly adapting fibers, differences in the ability of the deformed maxillary
      bone of cleft patients to conduct impulses, or other potential errors in the
      vibrometer.

PMID- 8134427
TI  - Bone grafting at the stage of mixed and permanent dentition in patients with
      clefts of the lip and primary palate.
AB  - Secondary bone grafting of a residual alveolar cleft has become a well
      established procedure. However, little attention has been paid to the benefits of
      these bone grafts in patients with clefts of the lip and alveolus only. This
      retrospective and comparative study includes 21 patients who had received a
      secondary or a late secondary bone grafting procedure from tibia and whose mean
      clinical and radiographic follow-up after the bone graft was 5.5 years. Eighteen
      patients treated without bone grafting served as controls. Length and width of
      cleft, presence or absence of permanent lateral incisor, size of nasal floor bony
      defect, and interdental alveolar bony height in the cleft area were investigated.
      The results showed that bone grafting was indicated particularly in wide clefts
      with missing lateral incisors. Eruption of a tooth close to the cleft was
      facilitated and the bony support for teeth neighboring the cleft was improved. In
      some cases, additional support of the alar base of the nose was achieved and
      closure of an oronasal fistula facilitated. A further advantage of bone grafting
      of clefts of the primary palate was that it might make it possible to insert a
      titanium implant carrying an artificial tooth in the cleft area.

PMID- 8134428
TI  - Comparison of craniofacial growth after rigid fixation with autogenous bone
      plates and with metal plates.
AB  - This study was undertaken to determine whether rigid fixation using autogenous
      cranial bone grafts restricts craniofacial growth less than metal plates in 7
      week-old Yorkshire pigs. A rectangular 10 x 20 mm segment of bone centered on the
      right coronal suture was resected. Animals were randomly assigned to one of three
      experimental groups: (1) rigid fixation across the defect using the bone graft
      rotated 90 degrees and attached with four microscrews; (2) rigid fixation across
      the defect using two microplates attached with four microscrews; or (3) no rigid
      fixation, with four microscrews placed to serve as radiologic markers. All
      animals were followed up with serial radiographs, and 8 months after the surgery
      direct measurements were performed on dry skull preparations. The greatest
      lengths were in the control group, followed by the bone plate and then the metal
      plate groups, but these differences were not statistically significant. The
      cranial width was significantly greater in the bone plate group, suggesting that
      a growth center may have been reoriented.

PMID- 8134429
TI  - A comparative study of the effects of biodegradable and titanium plating systems
      on cranial growth and structure: experimental study in beagles.
AB  - An experimental study was conducted in beagles to assess the effects of
      biodegradable and titanium plating systems on cranial growth and structure. Forty
      eight 9-week-old purebred beagles were used in this study. To avoid any effects
      of sexual dimorphism, we used only female beagles. The animals were divided in
      three groups: sham-operated controls, n = 16; beagles implanted with commercially
      available titanium plates and screws, n = 16; and beagles implanted with
      biodegradable plates and screws, n = 16. The biodegradable plating system
      developed by Storz Instrument Company (St. Louis, Mo.) for use in the
      craniofacial skeleton does not require another procedure to remove plates and
      screws once the healing process is completed. To assess the dynamics of changes
      in cranial growth under the influence of two different plating systems, we
      conducted two identical studies during two different time periods: 6 weeks and 12
      weeks. Using two different time frames allowed us to assess changes in the
      biodegradable material and in the bone and soft tissue surrounding this material.
      Statistical analysis revealed no significant differences in the gross cranial
      structure among the three groups. This finding suggests that the biodegradable
      plating system has no adverse effect on cranial growth. The material does resorb
      and/or disintegrate between 6 and 12 weeks after insertion. The rate of
      resorption is approximately 5.3 microns per day. The bone and soft tissue
      surrounding the biodegradable implant exhibited very limited inflammation and
      foreign body reaction. Bony overgrowth was frequently found over the plating
      system.

PMID- 8134430
TI  - Comparison of artifact from craniomaxillofacial internal fixation devices:
      magnetic resonance imaging.
AB  - This study compares artifact from craniomaxillofacial internal fixation devices
      in magnetic resonance images and examines heating and magnetic deflection effects
      on these devices. Stainless steel wires, microfixation plates of vitallium and
      titanium, and minifixation and mandibular reconstruction plates of stainless
      steel, vitallium, and titanium were evaluated. The plates were mounted on a dry
      skull and submerged in dilute copper sulfate solution. All images were obtained
      in duplicate by two independent, nonblinded teams of observers with a 1.5-T Signa
      magnetic resonance system. Each team ranked artifact size for each material by
      computerized measurement. The rank order of artifact size for each material
      within each fixation system group and between fixation groups was identical
      between the two teams. Bath and plate temperatures were recorded before and after
      imaging. Artifact production was related to hardware size and composition.
      Titanium hardware caused the least amount of "black-hole" artifact. Vitallium and
      stainless steel fixation devices of similar size produced significantly more
      artifact. No significant heating or magnetic deflection effects were seen with
      any of the fixation devices.

PMID- 8134431
TI  - Elevated IGF-II and TGF-beta concentrations in human calvarial bone: potential
      mechanism for increased graft survival and resistance to osteoporosis.
AB  - Calvarial bone grafts may have greater survival as donor tissue than bone from
      other sites. Furthermore, calvarial bone is resistant to osteoporosis. Because
      bone contains growth factors that may play an important role in the regulation of
      bone repair, we proposed that bone from calvaria may be enriched in one or more
      growth factors. To test this hypothesis, samples of bone from 10 men 64 years of
      age or older that were obtained at autopsy from three skeletal sites (calvaria,
      iliac crest, and vertebral body) were cleaned, extracted by demineralization, and
      assayed for growth factors insulin-like growth factor I, insulin-like growth
      factor II, and transforming growth factor-beta. Insulin-like growth factor II and
      transforming growth factor-beta concentrations were significantly higher in
      calvaria than in iliac crest or vertebral body. We conclude that the increased
      concentrations of growth factors in calvarial bone may lead to a greater capacity
      for bone repair and graft retention.

PMID- 8134432
TI  - Traumatic asphyxia.
AB  - Four patients showing classic physical stigmata of traumatic asphyxia were
      studied. Cervicofacial cyanosis and edema, subconjunctival hemorrhage, and
      multiple ecchymotic hemorrhage of the face, neck, and upper part of the chest
      were documented. Admission Glasgow coma scale scores ranged from 8 to 15. All but
      one had no associated injury. Skin discoloration resolved within 3 weeks.
      Complete resolution of subconjunctival hemorrhage occurred 1 month later. In our
      series, sore throat, hoarseness, dizziness, numbness, and headaches were common.
      Profound lower leg pitting edema, hemoptysis, hemotympanum, and transient visual
      loss were noted. Chest radiographic findings were normal in all patients.
      Microscopic hematuria was noted in one patient. Diagnosis is made from the
      history and characteristic appearance of the patient. Treatment is directed to
      the associated injury. Oxygen supplement with head elevation to 30 degrees is the
      mainstay of treatment. If the patient survives the initial insult, the prognosis
      is excellent.

PMID- 8134433
TI  - Intracranial nasal dermoid sinus cysts: computed tomographic scan findings and
      surgical results.
AB  - From July 1987 to January 1991, 14 patients, ages 1 to 19 years (mean 6 years),
      were seen with nasal dermoid sinus cysts, a congenital lesion with the potential
      for intracranial extension. Each patient was assessed clinically for cyst
      location, symptoms, associated craniofacial deformity, and other congenital
      anomalies. In 5 (36 percent) of the 14 patients, ages 4 to 48 months (mean 25
      months), computed tomographic scans indicated indirect signs of intracranial
      extension, which were confirmed intraoperatively and histologically in all 5
      patients. After neurosurgical consultation, a combined single-stage intracranial
      extracranial approach was used to excise the lesion. No perioperative
      complications occurred. Clinical assessment (follow-up 20 to 40 months, mean 31
      months), confirmed by postoperative CT scan 1 year after surgery, indicated no
      evidence of recurrence, residual skeletal contour defects, or deformity; forehead
      and nasal growth were qualitatively normal, and scar appearance was satisfactory.
      Our experience indicates that intracranial extension of nasal dermoid sinus cysts
      seen at a tertiary care referral center are not rare, that computed tomography
      scan permits accurate diagnosis, and that the single-stage intracranial
      extracranial approach to resection is effective and results in minimal morbidity.

PMID- 8134434
TI  - The use of lymphoscintigraphy in melanoma of the head and neck.
AB  - Lymphoscintigraphy has been shown to be of assistance in defining the lymphatic
      drainage pattern of melanoma. In this study, lymphoscintigraphy was performed on
      25 patients with primary melanoma (stages I and II at diagnosis) of the head and
      neck to determine whether the lymphatic drainage seen on lymphoscintigram was the
      same as the surgeon's expected lymphatic drainage. The lymphoscintigrams were
      discordant in 21 of the patients (84 percent) with drainage to a lymphatic basin
      not predicted clinically. Based on the discordant lymphoscintigram, a change in
      surgical therapy occurred in 13 of 21 patients (62 percent). Of the 25 patients,
      18 underwent prophylactic node dissections and 7 did not. Of the nodal basins
      removed, 27 of 38 nodal bases (71 percent) were seen on lymphoscintigraphy.
      Melanoma metastatic to lymph nodes was removed from nodal basins identified by
      the lymphoscintigram, but not predicted clinically, in two patients (8 percent).
      Historical anatomical patterns of lymph drainage and the clinical impression of
      experienced surgeons cannot reliably predict the pattern of lymphatic drainage in
      patients with melanoma of the head and neck.

PMID- 8134435
TI  - Versatility of a free inferior rectus abdominis flap for head and neck
      reconstruction: analysis of 200 cases.
AB  - Between 1984 and 1991, 200 inferior rectus abdominis muscle and musculocutaneous
      free flap transfers were performed for reconstruction of defects or deformities
      resulting from removal of cancer in the head and neck region. Primary
      reconstruction was performed in 190 of 200 cases (95 percent), and secondary
      reconstruction in 10 cases (5 percent). The most common indication was tongue
      cancer in 78 patients, followed by cancer of the oropharynx. Total flap necrosis
      occurred in 10 cases (5 percent) and partial necrosis in two cases (1 percent).
      Donor-site morbidity was minimal. One of the distinct advantages of this flap is
      that the volume of the muscle and/or the fatty tissue attached to a given skin
      paddle can be readily adjusted to suit individual requirements. This flap has
      proven particularly useful for complex or large tissue defects in the head and
      neck region.

PMID- 8134436
TI  - Condyle transplantation in free flap mandible reconstruction.
AB  - Fourteen patients requiring hemimandible resection were reconstructed with bone
      free flaps onto which the resected condyle was mounted as a nonvascularized
      graft. Postoperative mandible function, facial aesthetics, and patient symptoms
      were reviewed. The follow-up period ranged from 13 to 56 months (average 30.4
      months). Interincisal opening ranged from 25 to 52 mm (average 37.10 mm). Opening
      ability inversely correlated with a need for intraoral soft tissue replacement
      and with the administration of postoperative radiation therapy. Eight patients
      were available for late study of the transplanted condyle with lateral tomograms
      and computed tomographic scans. Condyle volume diminished considerably in some,
      but this did not correlate with a decrease in function. Dual joint function and
      preoperative occlusion were maintained long term with this technique. Aesthetic
      results were enhanced by the contribution of the transplanted condyle to improved
      accuracy of free flap bone graft fabrication and insetting. There were neither
      postoperative morbidity nor abnormal symptoms due to the use of the condyle as a
      nonvascularized graft. This study demonstrates the effectiveness and safety of
      condyle transplantation in free flap mandible reconstruction.

PMID- 8134437
TI  - The shape of a normal smile: implications for facial paralysis reconstruction.
AB  - Sophisticated smile reconstruction for facial paralysis requires an understanding
      of the facial movements during a normal smile. This study analyzes the direction
      and extent of movement of the upper and lower lips, nasal labial folds, and nasal
      base during smiling. Twenty normal subjects were analyzed using cine studies. A
      stop frame vector analysis was done on reference points on the lips and lower
      face. The greatest movement occurred at the commissure and upper lip.
      Intersubject variation in direction and extent of movement is great. Intrasubject
      variation in movement in comparing left and right sides was also quite large.
      Techniques of facial paralysis reconstruction that apply forces to the mouth,
      which mimic the vectors of movement on the patients' normal side, are most likely
      to provide a symmetrical smile reconstruction.

PMID- 8134438
TI  - Anesthetic practices in ambulatory aesthetic surgery.
AB  - Although ambulatory aesthetic surgery is commonly practiced and information
      concerning methods of anesthesia is readily available, little is known about the
      prevalence of various anesthetic practices and whether such practices differ
      according to the location of surgery. To obtain this information, we sent a
      carefully structured, 16-page, 69-item questionnaire to the members of the
      American Society for Aesthetic Plastic Surgery. Six hundred four (76.6 percent)
      of the 789 actively practicing members returned questionnaires, an exceptionally
      high response rate. Of interest are the following findings. More than 50 percent
      of the respondents operate in their offices half or more of the time. About one
      half never perform aesthetic surgery in the hospital. Free-standing ambulatory
      surgical facilities are used less frequently. A wide range of laboratory studies
      are ordered routinely, regardless of the location of surgery or age of the
      patient. Local anesthesia with intravenous sedation is widely used in all
      settings. When employed for office surgery, neither a nurse anesthetist nor an
      anesthesiologist is present about one-third of the time. General anesthesia is
      used in half of the office surgical units and is administered by dedicated
      anesthesia personnel. About half of the time it is administered by an
      anesthesiologist and about half of the time by a nurse anesthetist. The intensity
      and methods of patient monitoring are similar in the office, in the hospital, and
      in a free-standing ambulatory surgical facility. Preoperative laboratory
      evaluation, monitoring, and the use of anesthetic agents are similar regardless
      of the surgical setting.

PMID- 8134439
TI  - Temporalis fascia grafts in open secondary rhinoplasty.
AB  - Parchment thin skin is a common problem associated with secondary rhinoplasty.
      When such skin is present, the underlying osseocartilaginous skeleton often
      becomes visible. Although many techniques have been used to treat the condition,
      we have found that an onlay graft of temporalis fascia is a most satisfactory
      method to cover the underlying osseocartilaginous framework or cartilage grafts.
      Temporalis fascia grafts have been advocated for this purpose in closed
      rhinoplasty; however, precise placement of the graft is difficult because the
      graft rolls. On the other hand, when used in open rhinoplasty, the graft may be
      placed accurately and secured under direct vision. This paper presents our
      experience with temporalis fascia grafts in open secondary rhinoplasties. Six
      female patients ages 31 to 57 underwent open secondary rhinoplasty. Five patients
      also had autologous cartilage grafts. Our average follow-up was 24 months; the
      minimum was 1 year, and the longest 7 years. All patients had excellent dorsal
      contours and osseocartilaginous irregularities were not observed. One patient
      developed a culture-proven nasal infection that responded successfully to
      antibiotics without removal of the fascia or cartilage graft, a result unlikely
      to occur when alloplastic materials are used. Biopsy of the temporalis fascia and
      cartilage grafts was obtained in one patient 12 months after placement.
      Microscopic examination confirms the long term viability of both grafted tissues,
      inasmuch as the temporalis fascia was vascularized and normal chondrocytes were
      present in the cartilage grafts. In summary, we have found that temporalis fascia
      grafts are a very satisfactory method for managing thin skin in open secondary
      rhinoplasty.

PMID- 8134440
TI  - Improving the latissimus dorsi myocutaneous flap with tissue expansion.
AB  - Although the latissimus dorsi myocutaneous flap is a safe and reliable technique
      for breast reconstruction, its versatility is limited when large cutaneous units
      are needed to resurface a heavily irradiated or scarred breast and chest wall.
      The thick back skin, in particular, may be unsuitable for reconstruction opposite
      either a hyperplastic or moderate sized but ptotic breast. Also, the likely need
      for a prosthesis can result in encapsulation and firmness. Expanding the
      latissimus flap has been suggested as a means of improving its aesthetic and
      reconstructive results. Indications for choosing an expanded flap in 10 patients
      included: (1) a need for autogenous tissue reconstruction of irradiated breast
      and chest wall tissues; (2) cutaneous coverage requirements that exceeded the
      availability of donor site skin; (3) the presence of a hyperplastic or ptotic
      contralateral breast that the patient preferred to match rather than alter; and
      (4) unavailability of an alternative flap such as a TRAM and unsuitability of an
      implant or expander without a flap. Results of this study in 10 patients
      requiring breast and chest wall reconstruction demonstrate that flap dimensions
      increased by approximately a factor of 1.5 after expansion. The latissimus flap
      was pre-expanded on the back before transfer in two patients when skin and soft
      tissues were inadequate, or was expanded post-transfer in eight patients for both
      immediate and delayed breast reconstruction. Eight patients underwent a total of
      two operations, including two who had nipple areolar reconstruction. Earlier in
      the series, two other patients had nipple areolar reconstruction performed as a
      third procedure. Mean follow-up was 15.1 months. Complications consisted of
      partial dehiscence of the donor site wound in one patient after transfer of an
      expanded flap measuring 16 x 28 cm; three patients developed symptomatic seromas
      requiring drainage. All patients had soft, nonpalpable implants and no distortion
      of the flap's shape. The application of tissue expansion techniques yields
      latissimus flaps that are notable for their capacious dimensions, thinned
      tissues, and improved pliability. Advantages include an avoidance of reduction or
      mastopexy procedures in patients with large, ptotic breasts and uncomplicated
      wound healing in those with a history of prior irradiation. Not all latissimus
      flaps need to be expanded, but some can be significantly improved when specific
      indications are present. Most importantly, expanded latissimus flaps appear to
      resist the early formation of periprosthetic encapsulation.

PMID- 8134441
TI  - The effect of smoking on muscle transposition.
AB  - Smoking has been shown to be a complicating factor in normal wound healing. Both
      nicotine and carbon monoxide adversely affect multiple stages of the healing
      process. From 1976 to 1990, 1034 muscle flap procedures were performed on 722
      patients on a single surgical service. A retrospective review of 300 patients
      completed; patients were divided into three groups: group 1, no smoking history;
      group 2, smokers for at least 10 pack/years but had quit for at least 1 year; and
      group 3, active smokers at the time of surgery. Patients were omitted who had
      diabetes, had received radiation therapy or chemotherapy, had a recurrent
      malignancy, or used steroids. A total of 300 consecutive patients were entered
      into the study. Active smokers were shown to have a complication rate
      significantly higher in the immediate postoperative period compared with
      nonsmokers and smokers who had quit. The most common complications were partial
      muscle necrosis and partial skin graft loss. This series suggests that active
      smoking at the time of muscle transposition significantly increases the rate of
      postoperative complications.

PMID- 8134442
TI  - Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double-blind
      study.
AB  - To evaluate the effect of hyperbaric oxygen therapy on chronic wound healing, 16
      otherwise healthy patients who had nondiabetic, chronic leg ulcers with no large
      vessel disease were included in a double-blind study. Patients were grouped
      according to age and then randomly assigned to two groups breathing either air or
      oxygen at 2.5 atmospheres of absolute pressure for 90 minutes 5 days per week for
      a total of 30 treatments. The wound area was copied onto transparent film
      covering the wound and then measured using only one matching wound from each
      patient. The mean decrease of the wound areas at weeks 2, 4, and 6 in the oxygen
      group were 6 percent (SD +/- 14), 22 percent (SD +/- 13), and 35.7 percent (SD +/
      17), respectively, and in the air group, 2.8 percent (SD +/- 11), 3.7 percent
      (SD +/- 11), and 2.7 percent (SD +/- 11), respectively, giving a p value less
      than 0.05 at week 4, and a p value less than 0.001 at week 6 between the groups
      using the Mann-Whitney U test. These data indicate that hyperbaric oxygen therapy
      may be used as a valuable adjunct to conventional therapies when nondiabetic
      wounds do not heal.

PMID- 8134443
TI  - Hyperbaric oxygen improves wound healing in normal and ischemic skin tissue.
AB  - The influence of hyperbaric oxygen on reepithelialization and on microvascular
      perfusion of wounds in normal and ischemic skin tissue was investigated by using
      a standardized model, in ears of hairless mice. Animals were treated within 2
      hours of wound creation and then twice daily with 100% oxygen at 2 atmospheres of
      absolute pressure. Ischemia was induced by ligating two of the three major
      vessels of the ear 2.5 days before wound creation. Wound surface area was
      measured every third day after wound creation. In addition, microvascular blood
      flow before and during the wound healing process was measured by scanning the ear
      with a new laser Doppler perfusion imager. In normal tissue (n = 13), hyperbaric
      oxygen therapy significantly accelerated wound healing by 2 days (p < 0.01) as
      compared with controls (n = 16). In ischemic tissue (n = 16), treatment with
      hyperbaric oxygen reduced time for reepithelialization in control animals (n =
      16) from 14.3 to 9.9 days (p < 0.001). Laser Doppler data showed no difference in
      tissue blood flow between treated and untreated animals. In comparison with
      normal tissue, wound healing in ischemic tissue was characterized by a reduced
      and less intense hyperemic response. These data suggest that hyperbaric oxygen
      therapy improves reepithelialization in normal and ischemic skin tissue. The
      beneficial effect is not associated with changes in microvascular perfusion and
      therefore is probably due to high arteriolar oxygen content and oxygen diffusion.

PMID- 8134444
TI  - Subpectoral gliding tissue flap.
AB  - By cadaver dissection, the anatomy of the connective tissue between the
      pectoralis major and the pectoralis minor muscle was studied. The possibility of
      creating a pedicled flap of gliding tissue based on the pectoral branch of the
      thoracoacromial artery was confirmed. The clinical relevance of this tissue was
      defined in nine patients. To avoid recurrent fibrosis after neurolysis of the
      structures of the brachial plexus in patients with recurrent pain syndromes, the
      envelopment of the neurolyzed nerves by a subpectoral gliding tissue flap was
      carried out and was successful in eight cases. After the transposition of the
      subpectoral gliding tissue flap, the remaining pectoralis major muscle showed
      only a small partial atrophy in the clavicular segment without any functional
      impairment; this was confirmed by physical examination and by electromyogram.

PMID- 8134445
TI  - An ethical dilemma: some will get through.

PMID- 8134446
TI  - Hemorrhagic cyst of the orbit as a long-term complication of prosthetic orbital
      floor implant.

PMID- 8134447
TI  - Reconstructive surgery after hemilaryngectomy for recurrent thyroid cancer using
      a free jejunal patch-graft.
AB  - This case report describes the third recurrence of a poorly differentiated
      follicular thyroid carcinoma that led to destruction of the thyroid cartilage.
      Curative surgery required hemilaryngectomy. Because of three previous operations
      (including neck dissection) and repeated external radiation, the typical
      laryngoplastic procedures and muscle flaps were not applicable. We therefore
      employed a stretched jejunal patch to cover the defect so that the neoglottic
      slit rendered respiration and phonation possible. Thus this approach resulted in
      functional reconstruction and obviated the need for a tracheostoma. We conclude
      that the use of a jejunal transplant represents a viable alternative to local
      reconstruction, particularly in cases complicated by previous surgery and
      external radiation.

PMID- 8134448
TI  - Ectopic hematoma formation complicating transverse rectus abdominus
      musculocutaneous flap breast reconstruction.

PMID- 8134449
TI  - Use of a pedicled parascapular flap combined with latissimus dorsi muscle for
      coverage of the forearm and reconstruction of elbow flexion.

PMID- 8134450
TI  - Heel coverage with a T-shaped distally based sural island fasciocutaneous flap.
AB  - Two cases of heel damage that were reconstructed with a T-shaped distally based
      island fasciocutaneous flap in the sural area are presented. This flap is
      vascularized by the distal sural arterial network. The advantages of this flap
      are: (1) It does not sacrifice any major arteries of the leg. (2) It covers the
      whole calcaneal area with a one-stage operation. (3) It can be elevated without
      losing any nerve sensitization in the leg. (4) The donor site can be closed with
      primary sutures when the flap is small enough. We conclude that our procedure is
      suitable for reconstructing soft tissue defects of the calcaneal area.

PMID- 8134451
TI  - Correction of asymmetric nostrils (alae) by columella transposition.
AB  - A new method for correction of asymmetric alae is presented. Asymmetric alae
      frequently follow nasal, columellar, and alar reconstruction, and the resulting
      distortion can pose a reconstructive dilemma. Correction of these deformities can
      require complex composite grafting or tissue rearrangement procedures. By
      transposing the columella, we have equalized asymmetric nostrils without
      introducing new tissue to the region. Although not appropriate to all types of
      alar discrepancy, this novel method, where applicable, is safe, reliable, and
      does not produce significant visible scarring or donor site morbidity.

PMID- 8134452
TI  - Free vascularized mesentery transfer for closure of wide peritoneal wall defects.
AB  - The repair of large abdominal defects can often present problems related to the
      availability of local tissues adequate for filling the gap without creating high
      abdominal tension and pressure. The use of a free vascularized mesentery flap for
      restoration of the abdominal wall, in a case of an infiltrating carcinoid of the
      right upper and middle abdomen, is reported. After anastomosing the mesentery
      donor vessels to the deep inferior epigastric artery and vein, the subcutaneous
      and cutaneous layers were sutured primarily. Closure of the peritoneal cavity by
      means of vascularized undamaged visceral peritoneum should avoid infection and
      the formation of adhesions.

PMID- 8134453
TI  - Pregnancy and residency.

PMID- 8134454
TI  - Leprosy and squamous cell carcinoma.

PMID- 8134455
TI  - The prevention of pressure ulcers.

PMID- 8134456
TI  - Lid splitting incision for dermoid cyst.

PMID- 8134457
TI  - Muscle-flap coverage for infected peripheral vascular prostheses.
AB  - Infection in a peripheral vascular prosthesis continues to be a serious
      complication in arterial reconstructive surgery and threatens the patient with
      loss of either limb or life. Infection rates at major centers are now low,
      ranging from 1 to 6 percent; however, limb loss and mortality rates for this
      complication range from 25 to 75 percent depending on the location of the graft
      and the extent of the infection. The use of muscle flaps in the management of
      acute wounds, infection-prone wounds, exposed orthopedic hardware, and
      osteomyelitis is now commonplace. Transposed muscle has been shown to be well
      vascularized tissue that improves healing time and decreases local wound
      bacterial counts. After considering the preceding facts, we used muscle flaps for
      coverage of infected peripheral vascular prostheses in a highly select group of
      patients. These patients were "end of the line," and last-ditch efforts were made
      to salvage life or limb. Twenty-four infected vascular grafts in 20 patients have
      been analyzed. Ages ranged from 52 to 87 years. All patients had grade 3, stage
      I, II, or III peripheral graft infections, as previously defined by Szilagyi and
      modified by vonDongen. Aortofemoral reconstruction was the most common initial
      bypass procedure (14), followed by femoral popliteal (6), axillofemoral (2),
      iliofemoral (1), and subclavian/subclavian bypass (1). Staphylococcus aureus was
      the most common infecting organism. Muscles used for coverage were the rectus
      femoris (13), the sartorius (9), the rectus abdominis (1), and the pectoralis
      major (1). The graft material was composed of Dacron in 16 instances and
      polytetrafluoroethylene in 8.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134458
TI  - The distally based superficial sural artery flap.
AB  - The distally based superficial sural artery flap, first described as a distally
      based neuroskin flap by Masquelet et al., is a skin island flap supplied by the
      vascular axis of the sural nerve. The aim of this paper is to refine the surgical
      technique in order to establish the reliability of this flap. We treated 20
      patients with 21 distally based superficial sural artery flaps, including 2
      fascial flaps. All flaps survived. Most flaps showed slight venous congestion. In
      the largest flap (10 cm wide by 13 cm long), edema lasted 2 months. In the flap
      whose pedicle was raised without the deep fascia, there was necrosis at the
      distal tip of the flap. The advantages are the following: The blood supply is
      reliable, elevation is easy and quick, and major arteries are not sacrificed.
      This new flap may be useful in selected circumstances.

PMID- 8134459
TI  - Reconstruction of the traumatized leg: use of distally based free flaps.
AB  - Microvascular free-tissue transfer is often employed to achieve limb salvage in
      traumatic leg wounds. Previous experience has shown that one cause of flap
      failure is placement of the microvascular anastomoses within the zone of injury
      and subsequent thrombosis. This observation has prompted surgeons to perform
      anastomoses on the proximal uninjured recipient vessels. However, access to the
      vessels distal to the injury site is often technically easier. An assessment was
      made of 23 free flaps used for leg reconstruction to evaluate the success of
      performing microvascular anastomoses distal to the zone of injury. Twenty-one
      flaps with distal anastomoses were successful (91 percent). Distally based free
      flap reconstruction provides an acceptable alternative to the commonly employed
      proximal approach.

PMID- 8134460
TI  - Improving reemployment rates after limb salvage of acute severe tibial fractures
      by microvascular soft-tissue reconstruction.
AB  - Patients with severe open tibial fractures may have a low rate of reemployment
      after reconstruction. Sixty-five limb-salvage patients were followed for at least
      2 years to determine the factors that influence future employment. The preinjury
      conditions found to influence reemployment included age less than 40, higher
      education, and white-collar employment. Early postinjury reconstruction and
      established bone continuity are advantageous to the patient, and the likelihood
      of reemployment is improved. Reconstructive surgeons may improve employment rates
      by early soft-tissue coverage, bone grafting (immediate cancellous or free bone
      transfers), and complete healing. Ambulation follows if bone continuity is
      established early, and the patient has gained an early advantage on the way to
      employment and a purposeful future. The reemployment rate has improved to 67
      percent in the 15 limb-salvage patients reconstructed after the initiation of
      aggressive intervention by the reconstructive surgeon. This equals the
      reemployment rate of traumatic below-knee amputees previously reported.

PMID- 8134461
TI  - Vascular freezing--a new method for immediate and permanent vasospasm relief: an
      experimental study in the rat.
AB  - Although much work has been done on the etiology and prevention of vasospasm, a
      spasmolytic agent capable of firmly protecting against or reversing vasospasm has
      not yet been found. In this paper, we describe a new physical method of treating
      vasospasm. It consists of directly freezing the arterial walls. Experiments were
      performed on the epigastric artery of 40 female Sprague-Dawley rats. A vasospasm
      was created by mechanical vessel manipulation. The vasospasm was treated by
      freezing the vessel walls with a dermatologic hand-held liquid nitrogen spray.
      Vascular spasm and patency controls were made immediately after thawing and 30
      minutes and 3, 10, and 120 days after freezing. Epigastric island flaps were
      harvested based on the frozen artery at 3, 10, and 120 days after the freezing
      procedure. Histologic studies also were effectuated 3, 10, and 120 days after the
      freezing procedure. Relief from vasospasm was instantaneous and permanent. After
      freezing, almost all the cells in the media and endothelium died and the
      adrenergic fibers degenerated. This was followed by a phagocytic debridement,
      complete regeneration of the endothelium, and a limited regeneration of the
      muscle fibers in the media. The adrenergic innervation was recovered, and no
      alterations in the adrenergic fibers distal to the lesion were noted at any time.
      None of the arteries examined underwent thrombosis, and all the flaps harvested
      survived very well, indicating that the vascular bed distal to the site of the
      freezing was normal. This vascular freezing technique may well have clinical
      applications for microsurgical transfers and for the prophylactic treatment of
      vasospasm disease. However, its indications still require clarification.

PMID- 8134462
TI  - Sonographic evaluation of dermis and subcutaneous tissue during and after skin
      expansion.
AB  - Soft-tissue thickness modifications were evaluated by high-resolution ultrasound
      sonography in six patients undergoing skin expansion, with the aim of
      investigating the possible use of this noninvasive method in the routine
      monitoring of soft tissues during and after skin expansion. Both during expansion
      (decrease) and in the postoperative period (increases up to 100 percent or more
      of the baseline preoperative value), changes in fat thickness occurred faster and
      were greater in magnitude than those in dermal tissue, overall gradual and
      limited. In our series, the values of fat thickness ranged between 44 (at full
      expansion time) and 140 percent (2 months after expander removal), with a highly
      significant difference (p = 0.0003), while dermis thickness values ranged between
      83 and 114 percent, respectively, showing no significant difference (p = 0.71).
      Some echo-structural dermal modifications were found by the 20-MHz probe at full
      skin expansion only. High-resolution ultrasound sonography may be proposed as a
      noninvasive method in the routine monitoring of soft tissues during and after
      skin expansion.

PMID- 8134464
TI  - Factors in adopting a new technique.

PMID- 8134463
TI  - Extensor tenolysis: a modern version of an old approach.
AB  - The concept of tenolysis has been in existence for at least 50 years. Its
      function is to free tendon from posttraumatic scar tissue. To retard the
      recurrence of rescarring, membrane interposition between tendon and bone has been
      recommended. In the setting of postfracture extensor tenolysis, I prospectively
      employed a 3-mm section of passive Hunter rod as an interpositional material in
      eight consecutive patients. After an average follow-up of 23 months, the patients
      maintained 92 percent of operatively attained motion; only 56 percent was
      maintained in six patients without membrane interposition. There was no instance
      of rod dislocation, rod removal, or adverse silicone reaction. Extensor tenolysis
      with silicone membrane (Hunter rod) interposition is more predictable and
      enduring than tenolysis alone.

PMID- 8134465
TI  - Osseointegration and the plastic surgeon: a time for reflection.

PMID- 8134466
TI  - Progressive hemifacial atrophy in a patient with lupus erythematosus.
AB  - This is a single case report describing a young woman with progressive facial
      atrophy that began at age 15. After she underwent commissuroplasty and collagen
      injection at age 29, her symptoms continued to progress, and she was ultimately
      shown to have serologic evidence of systemic lupus. She had a "remission of
      symptoms" after commencement of medical treatment (chloroquine and topical
      steroids) for her lupus. The association of progressive hemifacial atrophy and
      lupus is not new. This case and other cases associated with different autoimmune
      diseases suggest an autoimmune collagen-vascular origin for some cases of
      progressive facial atrophy. Furthermore, there is a need to modify the surgical
      approach in light of concurrent disease.

PMID- 8134467
TI  - Multiple-suture synostosis subsequent to ventricular shunting.

PMID- 8134468
TI  - Bilateral brachial plexus palsy after immediate breast reconstruction with TRAM
      flaps.
AB  - Although most postoperative upper extremity neuropathies are caused by extremes
      of position or intraoperative manipulation of the arm, nerve injury is possible
      without either of these. Pedicled TRAM flap surgery, during which no axillary
      retraction or hyperabduction of the arm is used, is not free of risk for neural
      injury. More studies are needed to specifically define risk-related maneuvers for
      these and other anesthetized patients.

PMID- 8134469
TI  - Use of the splenius capitis muscle flap for reconstruction of the posterior neck
      and skull in complicated Arnold-Chiari malformation.
AB  - A previously unreported muscle flap using the splenius capitis muscle is
      described. The flap proved to be of value in management of a difficult case of
      recurrent CSF leak complicating suboccipital craniectomy for the treatment of
      Arnold-Chiari malformation. The dura was repaired with a fasciae latae graft, and
      splenius capitis muscle flaps were used to obliterate the dead space and to
      complete the operative correction. This reversed a life-threatening situation
      while preserving the muscles' function and yielding a good cosmetic result. Flap
      anatomy and design are described for the success of this reconstruction.

PMID- 8134470
TI  - Preexpansion galeal scoring.
AB  - Preexpansion scoring releases the inflexible galea, permitting more rapid
      expansion of the scalp. In addition, when comparing this procedure with
      conventional scalp expansion, patients reported less pain when the galea was
      incised prior to insertion of the tissue expanders.

PMID- 8134471
TI  - Single-stage reconstruction of soft-tissue defects including the Achilles tendon
      using the dorsalis pedis arterialized flap along with the extensor digitorum
      brevis as bridge graft.
AB  - Open ruptures of the Achilles tendon with loss of the tendon and the overlying
      skin are very difficult to treat. They pose the problems of (1) combating
      infection, (2) providing soft-tissue cover, and (3) bridging the gap in the
      tendon. They are generally managed as multi-staged procedures. Once the infection
      is brought under control with debridement and antibiotics, skin cover is provided
      by local transposition flaps, distant pedicle flaps, or free-tissue transfer with
      microvascular anastomoses. The tendon itself is repaired later by one of the
      conventional techniques. More recently, composite free-tissue transfers repairing
      the skin and tendon in a single stage have been reported. We describe a simple
      and very reliable procedure using a dorsalis pedis island flap which provides a
      vascularized, innervated musculotendinous unit (i.e., extensor digitorum brevis)
      to bridge the gap in the Achilles tendon and thin, mobile skin and fascia to
      close the defect in the skin. Two cases are presented, including the technical
      details, advantages, and limitations of this procedure.

PMID- 8134472
TI  - Emergent reuse leech therapy: a better method.
AB  - Tissues threatened by venous congestion often can be saved by timely leech
      therapy. Methods to restimulate sated leeches, particularly emergently, are only
      poorly described in the nineteenth-century literature. Sated leeches were purged
      of their blood meals by (1) posterior crop incision, (2) hypertonic saline (3
      percent) immersion, (3) gentle finger pressure emesis, or (4) wood ash exposure.
      Their ability to reattach and refeed with or without serotonin stimulation was
      evaluated. All 20 leeches (100 percent) purged by posterior crop incision
      reattached, with 75 percent refeeding. After purging again, 87 percent of these
      refed leeches reattached, with 46 percent refeeding for a third time. Those
      leeches which did not initially refeed were exposed to serotonin 10 microM with
      100 percent reattaching and 40 percent refeeding. None of the leeches purged by
      hypertonic saline immersion regurgitation reattached or refed. A single leech
      purged by finger pressure emesis reattached (20 percent) but did not refeed.
      After exposure to serotonin, two (40 percent) of each saline and finger pressure
      group reattached, with neither of the hypertonic saline group refeeding, while
      both finger pressure-purged leeches refed, consuming a meal 38 percent (+/- 29
      percent) of original meal. None of those leeches which refed would reattach or
      refeed a third time. None of the wood ash-purged leeches reattached or refed even
      with serotonin exposure. The best method of purging leeches of their blood meals
      for emergent reuse is by posterior crop incision. Additional refeeding behavior
      can be achieved by immersion in serotonin 10 microM for 20 minutes.

PMID- 8134474
TI  - Itinerant foreign surgical teams and physicians in Mexico.

PMID- 8134473
TI  - Preoperative marking of cutaneous capillary malformations.

PMID- 8134475
TI  - Endoscopic implant evaluation and capsulotomy.

PMID- 8134476
TI  - Breast implants and trauma.

PMID- 8134477
TI  - A simplified two-step approach to nipple-areola reconstruction.

PMID- 8134478
TI  - Temporary fixation of facial implants.

PMID- 8134479
TI  - Reconstruction of a cheek defect with a forehead flap in one stage.

PMID- 8134480
TI  - The fallacy of an experimental model in face lifting.

PMID- 8134481
TI  - Oral premedication for local anesthesia in plastic surgery: prospective,
      randomized, blind comparison of lorazepam and temazepam.
AB  - Patients undergoing plastic surgical procedures under local anesthesia as
      inpatients were entered into a phase III randomized, blind trial designed to
      compare two commonly used oral premedications, lorazepam and temazepam. The
      effects of the drugs on each patient's memory, pain, sedation, and anxiety were
      assessed by questions asked of the patient, the nurse, and the surgeon. Analysis
      was based on 100 randomized patients. Lorazepam had a significantly greater
      amnesic effect (p < 0.0001), resulted in less pain with the local anesthetic
      injection (p = 0.006), and had a greater sedative effect than temazepam (p <
      0.0001, patient's assessment; p = 0.005, observers' assessments). There was no
      significant difference in anxiolysis between the two premedications (p = 0.20).
      If premedication is indicated, we advocate the use of lorazepam rather than
      temazepam as premedication for plastic surgical procedures to be performed under
      local anesthesia, provided there is adequate postoperative supervision.

PMID- 8134482
TI  - The health status of women following cosmetic surgery.
AB  - A retrospective study was performed to determine the frequency of new symptoms
      and diseases after silicone breast implantation. Questionnaires were mailed to
      826 women who made up a breast implant group (n = 516) and a control group who
      had undergone blepharoplasty (n = 124), liposuction (n = 111), or rhinoplasty (n
      = 75). Responses were obtained from 370 women (45 percent); however, 68 of these
      patients (18 percent) were considered ineligible. The overall response rate was
      59 percent for the breast implant group and 46 percent for controls. The 302
      eligible women included patients with silicone breast implants (n = 222) and
      controls (n = 80). Women with implants were significantly younger than controls,
      the median age of women with breast implants being 37 years compared with 46.5
      years for controls (p < 0.0001). We compared the incidence of 23 symptoms and 4
      connective-tissue diseases after cosmetic surgery in the two groups. The symptoms
      of swollen glands under arms (p < 0.05) and tender glands under arms (p < 0.01)
      were statistically more frequent in the breast implant group. The symptom change
      in skin color was more common in the controls (p < 0.001). The Bonferroni
      correction for multiple (27) endpoints adjusts the 5 and 1 percent significance
      cutoff points to 0.00185 and 0.00037, respectively, leaving only change of skin
      color significant at the 5 percent level on the adjusted data. No cases of
      scleroderma or lupus were found, and the incidence of arthritis was not
      significantly different between the implant and control groups.

PMID- 8134483
TI  - Aesthetic indications for botulinum toxin injection.
AB  - A clinical trial was undertaken to evaluate the effects of commercially available
      botulinum toxin on 14 hyperactive corrugator muscles, 14 procerus muscles, one
      case of congenital aplasia of the depressor labii inferioris muscle, and one case
      of iatrogenic injury to the ramus mandibularis branch of the facial nerve with
      paralysis of the depressor labii and mentalis muscles. Of the 31 muscles
      injected, 28 were appropriately paralyzed with the initial injection. The desired
      results were obtained in the 3 remaining muscles following a second injection.
      The ability to frown was nullified in all subjects, resulting in the elimination
      of glabellar lines. Facial symmetry was achieved in both patients with muscle
      imbalance. The average duration of the paralysis was 8 weeks, with a range of 2
      to 16 weeks. However, this period was prolonged in the latter part of the study
      with an adjustment of the toxin dose. Our results demonstrate that botulinum
      toxin injected into overactive facial muscles does produce a predictable and
      reversible paralysis and eliminates or ameliorates deep frown lines. We also
      illustrate its use in achieving facial symmetry in one patient with congenitally
      absent depressor labii inferioris and platysma muscles and in another with
      postrhytidectomy facial nerve paralysis.

PMID- 8134484
TI  - The incompetent external nasal valve: pathophysiology and treatment in primary
      and secondary rhinoplasty.
AB  - The size of any nasal airway depends not only on the width and contour of the
      septal partition and inferior turbinates but also on the position and stability
      of the lateral nasal wall under the pressure changes that occur during the
      dynamic process of ventilation. Thus any congenital or acquired weakness of the
      upper or lower lateral cartilages or their investing soft tissues may profoundly
      affect the ability to draw adequate volumes of air through the nose. Sixty-one
      surgical patients treated for incompetence of the external nasal valves
      (comprising the cutaneous and skeletal support of the mobile alar walls) are the
      subjects of this paper. Rhinomanometric data on 16 patients with "pure" external
      valvular incompetence showed a twofold increase in total mean nasal airflow
      following valvular reconstruction with septal cartilage or bone grafts or with
      composite conchal cartilage-skin grafts for patients with associated vestibular
      skin deficiencies. Seven patients with combined external valvular and septal
      pathology derived most of their postoperative airflow improvement from correction
      of the valvular defect. The external nasal valve may be a substantial cause of
      nasal airway obstruction in some patients; its pathophysiology and treatment are
      discussed in primary and secondary rhinoplasty.

PMID- 8134485
TI  - The Pierre Robin sequence: review of 125 cases and evolution of treatment
      modalities.
AB  - All children admitted to our hospital between 1964 and 1991 with a diagnosis of
      Pierre Robin sequence were divided into three groups according to the severity of
      their symptoms: group I: adequate respiration in prone position and bottle
      feeding; group II: adequate respiration in prone position but feeding
      difficulties requiring gavage; and group III: children with respiratory distress
      and endotracheal intubation and gavage. The presence of associated anomalies,
      prematurity, and psychomotor impairment was noted as well as the surgical
      interventions performed. We found 56 children (44.8 percent) in group I, 40
      children (32 percent) in group II, and 29 children (23.2 percent) in group III.
      Seventeen children (13.6 percent) died: 1 of 56 in group I, 4 of 40 in group II,
      and 12 of 29 in group III. Among the 125 patients, 57 presented at least one
      associated anomaly other than a cleft palate and the Pierre Robin triad. Thirteen
      deaths were found in this group (13 of 57 = 22.8 percent). Ten children were
      premature (10 of 125), and 6 of the premature infants died (60 percent). Twenty
      two children required at least one surgical procedure to relieve the upper airway
      obstruction. Among the 108 survivors in this study, 25 presented a psychomotor
      impairment (23.1 percent). The children admitted after 1986 were submitted to
      routine serial blood gases, oxygen saturation monitoring, and polysomnographic
      recordings. The therapeutic interventions were done earlier. Thirty-four children
      were followed after 1986: 14 in group I, 11 in group II, and 9 in group
      III.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134486
TI  - Sleep apnea following a pharyngeal flap: a feared complication.
AB  - Pharyngeal flaps are often used to correct velopharyngeal insufficiency. They
      produce a permanent partial obstruction of the velopharyngeal space. Respiratory
      obstruction and obstructive sleep apnea have been reported following this
      surgery. We undertook a study to find out the incidence of sleep apnea associated
      with pharyngeal flap surgery. Forty-one children (aged 2 to 22 years) admitted
      for a pharyngeal flap underwent a polysomnographic recording prior to their
      surgery. One child with Steinert's disease showed some episodes of obstructive
      apnea, and the surgery was canceled. Forty children underwent pharyngeal flap
      surgery, and polysomnography with continuous arterial saturation was repeated
      following surgery. Postoperative polysomnograms were normal in 26 patients (65
      percent) and abnormal in 14 patients (35 percent). Among the 14 abnormal
      patients, we found 6 with obstructive apneas, 6 with central apneas, and 2 with
      both central and obstructive apneas. Ten of the 14 abnormal patients were
      restudied in the following months. Eight children had normal recordings, while 2
      had central apneas. The 4 patients who declined a follow-up recording had no
      clinical symptoms of respiratory difficulty when sleeping. Of the 2 children with
      abnormal recordings on long-term follow-up, 1 is asymptomatic, while the second
      has persistent snoring, nocturnal awakening, sweating, and daytime lethargy. A
      section of his flap has been recommended. Independent analysis of arterial oxygen
      saturation revealed that the percentage of time with a saturation of less than 90
      percent identifies patients with clinically significant apneas. Our data show
      that significant sleep apneas following pharyngeal flaps may not be as frequent
      or permanent as previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134487
TI  - Tailoring velopharyngeal surgery: the influence of etiology and type of
      operation.
AB  - The results of 132 consecutive endoscopically selected pharyngoplasties were
      assessed. Depending on the size and shape of the velopharyngeal defect on
      attempted closure, patients had been allocated to one of four pharyngoplasties:
      (1) a superiorly based pharyngeal flap combined with a V-Y pushback of the soft
      palate (Honig), (2) a modified Hynes approach, (3) a superiorly based pharyngeal
      flap, or (4) a fish flap. Patients were categorized according to etiology as
      having cleft palate, submucous cleft palate, disproportion, or neurologic origin.
      Acceptable nasal resonance was found after 81 percent of the Honig operations, 81
      percent of the Hynes operations, and 63 percent of the superiorly based flap
      operations, vindicating the selection criteria based on palatal and pharyngeal
      wall movement. The fish flap operation was successful in only 50 percent and is
      not recommended. The cleft, submucous cleft, disproportion, and neurologic
      categories were equally well corrected by the Honig and Hynes operations. Side
      effects were common, with catarrh or snoring in 51 percent, difficulty breathing
      through the nose in 27 percent, and 9 percent requiring revision of their
      pharyngoplasty (6 of 53 Honig and 5 of 63 Hynes operations). The higher median
      age for those patients requiring pharyngoplasty revision (17 versus 10 years)
      suggests more cautious use in the older patient.

PMID- 8134488
TI  - Perioperative complications of superior pharyngeal flap surgery in children.
AB  - A 7-year retrospective review of perioperative complications associated with
      surgical correction of velopharyngeal insufficiency was carried out. A total of
      219 children who underwent surgery for velopharyngeal insufficiency between the
      years 1985 and 1992 were reviewed. Gender distribution was 58 percent male and 42
      percent female. The mean age was 9.6 years, with a range of 4 to 22 years, at the
      time of surgery. Fourteen cases (6.4 percent) were considered a difficult
      intubation. There were 36 patients with early complications (16.4 percent
      incidence). Of these, 18 had postoperative bleeding and 20 developed airway
      obstruction. Most of these episodes occurred in the first 24 hours. Three
      patients required reintubation. Nine children developed sleep apnea after
      discharge. Four patients required take-down of the pharyngoplasty, while 7 others
      had revision of the flap. There was 1 death in the 219 patients. In summary, most
      complications following surgical correction of velopharyngeal insufficiency in
      our institution occur in the early postoperative period and are the result of
      bleeding and/or airway obstruction.

PMID- 8134489
TI  - Bone differentiation in porous hydroxyapatite in baboons is regulated by the
      geometry of the substratum: implications for reconstructive craniofacial surgery.
AB  - Previous studies have shown the morphogenesis of bone in a porous hydroxyapatite
      substratum when implanted intramuscularly in baboons. This hydroxyapatite-induced
      osteogenesis model was used to study the effect of geometry and pore size of the
      substratum on bone differentiation. Two distinct geometric configurations of
      porous hydroxyapatite of different pore size were obtained after hydrothermal
      conversion of the calcium carbonate exoskeleton of corals (genera Porites and
      Goniopora). Substrata were blocks of hydroxyapatite in rod configuration of 200-
      and 500-microns pore size and granular hydroxyapatite (400 to 620 microns in
      diameter) of 200- and 500-microns pore size. A total of 64 granular
      hydroxyapatite implants and 32 hydroxyapatite rods were implanted intramuscularly
      in 8 subadult male baboons (Papio ursinus). Specimens were harvested on days 60
      and 90 and subjected to histologic and histomorphometric analysis. With the
      exception of an island of bone that formed in two implants of granular
      hydroxyapatite of 500-microns pore size, bone differentiation occurred only in
      blocks of hydroxyapatite in rod configuration of either pore size at both
      observation periods. The lack of bone formation in the granular hydroxyapatite
      indicates the critical role of geometry of the substratum in bone
      differentiation. These results in primates may have implications for the
      appropriate selection of porous bone substitutes for reconstructive craniofacial
      surgery in humans.

PMID- 8134490
TI  - Osseointegrated alloplastic versus autogenous ear reconstruction: criteria for
      treatment selection.
AB  - Fifty-five patients with major ear deformities were reconstructed during the
      period 1982-1993 with autogenous tissue. Fourteen patients were reconstructed
      with osseointegrated auricular prostheses during the period 1989-1993. Both
      procedures were done at the same institution by the same surgeon. The advantages
      and disadvantages of each approach were considered, and our criteria for
      treatment selection were developed. Our main indications for autogenous
      reconstruction include classical microtia, relatively normal lower one-third of
      the ear, patient preference, and less compliant patients. The main indications
      for osseointegrated alloplastic reconstruction include following major cancer
      extirpation, poor local tissue, absence of the lower half of the ear, salvage
      following unsuccessful autogenous reconstruction, and poor operative risks.
      Because of their success, osseointegrated auricular reconstructions should be
      added to the armamentarium of the reconstructive surgeon.

PMID- 8134491
TI  - Wound-healing complications after soft-tissue sarcoma surgery.
AB  - One-hundred and eighty patients undergoing limb-salvage surgery for soft-tissue
      sarcoma from 1986 to 1991 were assessed retrospectively for risk factors
      associated with major wound-healing complications. Twenty-three of 137 patients
      (16 percent) treated with primary direct wound closure sustained complications.
      In univariate analysis, the cross-sectional area of tumor resection, the use of
      preoperative irradiation, the width of the skin excision, a history of smoking,
      and a history of diabetes and/or vascular disease were associated with wound
      failure. Multivariate analysis revealed that preoperative irradiation (p = 0.04)
      and resection diameter (p = 0.017) accounted for the risk of complications.
      Eighteen additional patients were treated empirically with distant vascularized
      tissue transfer following preoperative irradiation because of concerns regarding
      potential wound complications. The lower complication rate in this group
      suggested that vascularized tissue transfer may be beneficial in lowering wound
      complication rates.

PMID- 8134492
TI  - Assessment of the abdominal wall after pedicled TRAM flap surgery: 5- to 7-year
      follow-up of 150 consecutive patients.
AB  - To define the long-term abdominal consequences of the TRAM flap procedure, 150
      consecutive patients were evaluated 5 to 7.5 years postoperatively. Of 137
      surviving patients, 135 (98.5 percent) returned a questionnaire (68 single
      pedicle, 63 double rectus harvest, and 4 single pedicle with contralateral
      microvascular augmentation) and 132 (96.4 percent) were examined and tested. By
      questionnaire, 64 percent noted overall improvement of the abdomen, 72 percent
      noted improved abdominal appearance, and 20 percent noted improved posture.
      Decreased abdominal strength was noted by 46 percent, and decreased exercise
      ability was noted by 25 percent. These figures were higher after double rectus
      harvest (60 and 35 percent) than after single rectus harvest (35 and 16 percent)
      (p = 0.005 and p = 0.014, respectively). Activities of daily living were rarely
      (4.0 to 5.8 percent) affected. Three of the patients had uncomplicated
      pregnancies and deliveries (two vaginal, one cesarean section). Situp performance
      was worse comparing postoperative patients with unoperated controls (p < 0.0005)
      and comparing double rectus harvest with single rectus harvest patients (p <
      0.0005). Comparing double rectus harvest patients with direct abdominal closure
      and those closed with mesh, there was a trend toward poorer situp performance in
      the mesh subgroup; however, this was not statistically significant. On
      examination, a classic post-TRAM hernia was not encountered in any patient, but
      three single-pedicle patients had asymptomatic diffuse bulges through the fascial
      harvest site, visible only on straining to do a situp. Eight patients (seven
      bilateral and one single pedicle) had varying degrees of abdominal laxity, but
      only one had operative correction of diffusely attenuated abdominal fascia
      following pregnancy and delivery. Examiners' ratings of aesthetic abdominal
      appearance were higher for postoperative patients than for unoperated controls (p
      = 0.05). The vast majority of patients considered the TRAM procedure worthwhile
      (93 percent) and continued to recommend it to others (96 percent).

PMID- 8134493
TI  - [Personality changes of neurotic patients as outcome of the treatment].
AB  - The present article attempted to assess the importance of outcomes which appeared
      during the treatment of 30 neurotic patients. This study specially concentrates
      on measures of emotional empathy, self-confidence and introspection. There were
      two surveys in the clinical group: before and after the treatment was completed.
      Data were compared with a control group, also consisting of 30 persons (15 male
      and 15 female) matched for age and education. All patients attending group
      psychotherapy were also treated by pharmacotherapy. As it appeared from the
      analysis before treatment high empathy in patients was found, but this declined
      after therapy, however it was still significantly higher than in the control
      group. The first survey revealed also that patients demonstrated lower levels of
      self-confidence and introspection. After treatment there were no important
      differences between the groups. Relationships between the studied qualities were
      not statistically significant.

PMID- 8134494
TI  - [The chronic fatigue syndrome].
AB  - The chronic fatigue syndrome (CFS) including myalgic encephalomyelitis and the
      postviral syndrome is a term used today to describe a not fully recognized
      disease characterized primarily by chronic or recurrent debilitating fatigue and
      various combinations of neuromuscular and neuropsychological symptoms. The term
      CFS has been introduced and defined by the Centers for Disease Control (CDC) in
      Atlanta. Fatigue is one of the most common symptoms in medicine, but CFS as
      defined by CDC has appeared to be quite rare in the general population.
      Researchers have suggested that the syndrome is a heterogenous immunologic
      disorder that follows viral infection, but despite numerous studies on the
      subject the etiologic factor of the syndrome is unknown. CFS is a controversial
      diagnosis. In a very high percentage of patients with the CFS depression, phobias
      or anxiety disorders have frequently preceded the onset of the chronic fatigue.
      There are many overlapping symptoms between CFS and major depression. Some
      clinicians suggest that it is not obvious that CFS can be distinguished from
      neurasthenia.

PMID- 8134495
TI  - [Twenty-five years of telephonic emergency service in Poland: the aim and role of
      the Telephone Helpline in the prevention of social pathology].
AB  - In 1992 Polish Telephonic Emergency Service celebrated its 25th anniversary. The
      first two posts of "Telefon Zaufania" (Confidence Telephone) started
      simultaneously but independently in Wroclaw and Gdansk in 1967. Both sought to
      serve people in psychological crisis. The Gdansk post became known as "Anonymous
      Friend" and it was run on a voluntary basis. In Wroclaw "Telefon Zaufania" was
      strictly professional, it was organized in the Psychiatric Clinical of the
      Medical Academy and manned only by psychiatrists. Today in Poland there are such
      telephone posts almost in all cities and larger towns. Since 1973 the Polish
      telephone posts belong to IFOTES (International Federation of Telephonic
      Emergency Service) and they follow the norms of IFOTES: anonymity, unselfishness,
      confidence and befriending callers. In 1990 their was organized the Polish
      Association of Telephone Service in order first of all to improve the quality and
      efficiency of their service, to coordinate their work and to co-operate with
      Polish and international centers. The major problems of callers in crisis are the
      same in all types of post: family conflicts, marital troubles, peer group
      problems, the lack of the sense life, suicidal thoughts, drink and/or drug
      addiction. In the prevention of social pathology "Telefon Zaufania" proves the
      first, often the only rescue line to people in psychological crisis.

PMID- 8134496
TI  - [Estimation of the levels of anxiety, emotional endurance and placement of
      control of female patients hospitalized with coronary disease].
AB  - Spielberger's State--Trait Anxiety Inventory, Z. Bizon's Questionnaire of
      Neurotic Symptoms as the indicator of emotional endurance and Rotter's Internal
      External Control Scale were used for the analysis of a problem concerning the
      mechanisms of psychological functioning of female patients hospitalized with
      coronary disease. 35 women suffering from coronary disease were examined, a
      control group consisting of 35 healthy women was also assessed. The results
      indicate significantly higher levels of anxiety both as a state and as a trait,
      lower level of endurance, and more externally placed control in the patients
      group in comparison with the control group. Additionally, patients strongly
      predisposed to anxiety tended to have an external sense of control, high level of
      anxiety, and low level of emotional resilience.

PMID- 8134497
TI  - [Comments on contemporary concepts of hypnosis and its application in
      psychiatry].
AB  - This paper is an overview of the concepts of hypnosis from the first descriptive
      accounts until the present, from a phenomenological and practical perspective.
      The authors described this phenomenon as a specific state of consciousness, which
      is engendered by a therapist. It is very important to note the difference among
      hypnosis, sleeping and wakefulness. This paper discusses the basic hypothesis of
      the origins of hypnosis e.g. "suggestive acting", theories of neodissociation,
      psychoanalytical, multidimensional and behavioural. The authors emphasizes the
      meaning of reducing the sphere of the consciousness in this state and it's
      limitation in case of suggestions, which are contradictory to the ethics and
      instinct of self-preservation represented by the patient. The essence of hypnosis
      is a specific state of rapport between the therapist and the passive patient. The
      authors remove from hypnosis any hint of mystery emphasising the methodological
      difficulties in reliable researches on this subject. Hypnosis is an useful
      instrument in the hands of a qualified and experienced therapist. It is
      particularly valuable in the therapy of drug dependences, some kinds of neurotic
      states, an anxiety and phobias, as in treating disturbances of personality.

PMID- 8134498
TI  - [Personality assessment of primary school children (VIII grade) with depressive
      features (preliminary description)].
AB  - 235 primary school children (VIII grade) aged about 14 years, meeting the
      criteria for depressive syndrome were assessed by the IPAT High School
      Personality Questionnaire of R.B. Cattell (14 factors version). Results show that
      the personality of adolescents with depressive syndrome is characterized by a
      tendency to isolation and conflictual relations with peers. The results point
      also to the difference between depressive girls and boys. Girls' personality has
      more features similar to adult depressive personality such as introversion,
      schizothymia, isolation and irritability. In boys only the scale of isolation was
      alleviated. It is planned to compare these results with the results of a control
      group of normal adolescents.

PMID- 8134499
TI  - [The course of affective disorders in different periods of life].
AB  - The aim of the following research was to estimate the dependence of the course of
      affective disorders on sex and age. The material used in this study came from 760
      medical records of 100 patients with affective disorders. The proportions of
      depressive and mania phases were estimated both for men and women in 4 groups of
      age: I to 29 years; II--30-44; III--45-59; IV--60 years and over. It was found
      that the proportion of episodes of mania decreased from 71.8% in group I to 26.0%
      in group III and increased to 28.9% in the oldest group. The proportional changes
      of depressive episodes where noted. In the first group there were episodes of
      mania prevalent both in male and female patients. In group II depressive episodes
      dominated (60.6%) among women and there were 53.9% manias among men. In group III
      depressive episodes were prevalent among both sexes. In group IV depressive
      phases constituted the majority (75.2%) among women and 59.5% among men.
      Analyzing the clinical picture of depression it was found that men from group I
      and III more often mentioned suicidal thoughts and demonstrated fear and suicidal
      attempts. In group IV women more often then men exhibited fear, suicidal thoughts
      and attempts. In the mania phase men from group I exhibited more symptoms then
      women. In group II the clinical picture of mania were similar for both sexes. In
      group III women with mania were more seriously ill then men--they exhibited
      flight of ideas, aggression, dysphoria, they abused alcohol and took part in
      criminal activity. In the oldest group the clinical picture of mania was similar,
      only women exhibited flight of ideas and aggression more often then men.

PMID- 8134500
TI  - [Phototherapy for winter depression: report of three cases].
AB  - Phototherapy was administered to three female outpatients with seasonal affective
      disorder (winter depression), according to the DSM III-R criteria. The intensity
      of light was about 2.500 lux in two, and 1.500 lux in one cases at the eyes
      level. The treatment has shown to be very effective. Antidepressant response was
      observed after about one week of treatment. A short-lasting switch into hypomania
      was observed in one case.

PMID- 8134501
TI  - [Drug resistance in endogenous depression. Part I. Refractoriness to
      antidepressants in patients with depression admitted to a psychiatric clinic for
      the first time].
AB  - The efficacy of antidepressive treatment (mainly pharmacotherapy) was evaluated
      among 284 patients, admitted for the first time to the hospital with the
      diagnosis of endogenous depression. The first antidepressant therapy was found
      effective in 58% of the patients. Furthermore treatment with other
      antidepressants in the patients not responding to the initial therapy was
      successful in 57% of the cases. Drug resistance (defined as no therapeutical
      effect after 2 adequate courses of antidepressant treatment) was established in
      7% of this sample. It was established that the drug resistance is more frequent
      after the 45th year of life. No relation between the drug resistance and sex,
      type of affective disorder, life events or somatic disorders were found.

PMID- 8134502
TI  - [Clinical pharmacokinetics of tricyclic antidepressants. Part I. Pharmacokinetic
      properties].
AB  - Pharmacokinetic properties of tricyclic antidepressants (TCA) and factors
      changing pharmacokinetics of these drugs were presented. The following factors
      were discussed: age, genetically determined rate of metabolism and TCA
      interaction with co-administered drugs. As a consequence of these factors
      alterations mainly in elimination of TCA are observed. It leads to large
      interindividual variation in TCA plasma concentrations and lack of correlation
      between TCA concentration and dosage.

PMID- 8134503
TI  - [Was forensic psychiatry in Poland abused for political reasons?].
AB  - With the aim of answering the question whether Polish forensic psychiatry was
      misused for political purposes the authors formulate several discussion question
      and try to describe the conditions protecting human rights of the person who is
      of interest to psychiatry and the law. The difficulties with formulating the
      concepts which define "misuse" are a result of the lack of more in-depth
      empirical research into this issue, the danger of using judgmental arguments and
      the need to retain an emotional distance in relation to the problem. While
      avoiding an unequivocal answer to this question several specific questions were
      selected, which may be helpful in formulating a more general assessment. The
      complexity and the polymorphous nature of the conditions which must be fulfilled
      before one may speak of the realization of the guarantee of human rights within
      the field of forensic psychiatry makes it possible to accept the notion that
      simply the existence of exterior laws regulating this legal issue is not enough
      to guard against the misuse of psychiatry. Nevertheless, the moral standards of
      psychiatrists, the legal functioning of the country and the adequacy of current
      laws in relation to medical knowledge are no less important. Final and
      unequivocal assessment of the role played by forensic psychiatry in the socio
      political life of Poland in the past several decades may not be conducted without
      unbiased and scientific empirical research.

PMID- 8134504
TI  - An idiot savant calendrical calculator with Gilles de la Tourette syndrome:
      implications for an understanding of the savant syndrome.
AB  - We describe the existence of the savant syndrome in association with Gilles de la
      Tourette's Syndrome (GTS). The presentation of savant abilities is typical of
      that previously described. Similarities between autism, the disorder most
      characteristically associated with savants, and GTS in terms of obsessionality
      are noted. Previously reported psychological studies of autistic savants are
      briefly reviewed and, together with evidence from neuroimaging in GTS, obsessive
      compulsive disorder (OCD), and autism, used to support a model of the
      underpinnings of savant skills.

PMID- 8134505
TI  - The course and outcome of depression in different cultures: 10-year follow-up of
      the WHO Collaborative Study on the Assessment of Depressive Disorders.
AB  - The World Health Organization's study on depressive disorders in different
      cultures began in 1972. Cohorts of depressed patients were identified in Basle,
      Montreal, Nagasaki, Teheran and Tokyo. The patients were assessed using
      standardized measures of social and clinical functioning. Ten-year follow-up data
      on clinical course, service contact, suicidal acts and social function outcomes
      were available for 439 (79%) patients. Over one-third (36%) were re-admitted at
      least once in the follow-up period, half of whom (18%) had very poor clinical
      outcome. Twenty-four per cent suffered severe social impairment for over half the
      follow-up period, and over one-fifth (21%) showed no full remissions. The best
      clinical course (one or two reasonably short episodes of depression with complete
      remission between episodes) was experienced twice as frequently in patients with
      a diagnosis of endogenous (65%) as in those diagnosed as suffering from
      psychogenic depression (29%). Among all patients, a fifth (22%) had at least one
      episode lasting for more than 1 year, and 10% had an episode lasting over 2 years
      during follow-up. Death by suicide occurred in 11% of patients, with a further
      14% making unsuccessful suicide attempts.

PMID- 8134506
TI  - The Prince Henry Hospital Mood Disorders Unit.

PMID- 8134507
TI  - The application of differential cloning techniques in post-mortem studies of
      neuropsychiatric disorders: a way ahead.

PMID- 8134508
TI  - Sleep abnormalities in schizophrenia: pathophysiological significance.

PMID- 8134509
TI  - The MRC Needs for Care Assessment: progress and controversies.

PMID- 8134510
TI  - Kraepelin revisited: a reassessment and statistical analysis of dementia praecox
      and manic-depressive insanity in 1908.
AB  - A meta-analysis was carried out on 53 cases of dementia praecox (DP) and 134
      cases of manic-depressive insanity (MDI) originally diagnosed by Kraepelin or his
      collaborators in Munich in 1908. The original case material was coded in terms of
      Present State Examination syndromes and analysed statistically for internal
      consistency and discrimination between the two diagnostic entities. Kraepelin's
      DP and MDI were found to define homogeneous groups of disorders which could be
      clearly distinguished from one another. A CATEGO re-classification of the cases
      revealed an 80.2% concordance rate between Kraepelin's diagnoses and ICD-9.
      Cluster analysis of the original data reproduced closely Kraepelin's dichotomous
      classification of the psychoses but suggested that DP was a narrower concept than
      schizophrenia today, while MDI was a composite group including both 'typical'
      manic-depressive illnesses and schizoaffective disorders.

PMID- 8134511
TI  - Old data, new interpretation: a re-analysis of Sir Aubrey Lewis' M.D. thesis.
AB  - Sir Aubrey Lewis studied 61 depressives in considerable detail, principally cross
      sectionally but also by reviewing progress. He concluded that he could find no
      qualitative distinctions between the depressed patients and thus established
      himself as a strong and influential advocate of the unitary view of depression
      (i.e. that depression varies dimensionally, not categorically). Subsequently,
      Kiloh & Garside (proponents of the binary view of two depressive 'types') coded
      the Lewis data and undertook a principal components analysis. They claimed
      success in distinguishing 'endogenous' and 'neurotic' depressive types within
      Lewis' sample. In this paper we re-analyse the data set using both a latent class
      categorical approach and mixture analyses. We suggest that any demonstration of
      sub-types was limited by relative homogeneity of the sample (in that up to 80%
      had probable or possible psychotic conditions), and by Lewis rating a number of
      important features (e.g. delusions) dimensionally rather than categorically.
      Nevertheless, we identify one categorical class (essentially an agitated
      psychotic depressive condition) and a residual (presumably heterogeneous) class.
      The presence of those two classes was supported by demonstrating bimodality in
      composite scores derived from the fourteen differentiating clinical features (and
      not evident when all clinical features were considered), and formally confirmed
      by mixture analyses. Membership of the categorical class was determined
      principally by psychotic features (delusions and hallucinations) and by
      objectively-judged psychomotor disturbance, and we consider the nature of that
      'class'. Lewis' data set is unusual (in having self-report and observationally
      rated data), and historically important in demonstrating that conclusions may
      depend on the choice of variables examined and analytical approaches.

PMID- 8134513
TI  - Single spies and battalions: the clinical epidemiology of mental disorders.
AB  - Clinical epidemiology, a term that has been variously defined, is used here to
      refer to a discipline which, commencing with examination and diagnosis of the
      individual patient who presents in medical practice, proceeds to study the
      occurrence of similar, possibly connected cases in the local community, and in so
      doing may provide hypotheses for population-based studies of disease and its risk
      factors. While the relevance of this discipline to the modern practice of
      clinical psychiatry remains largely unexplored, its importance in the search for
      causes of mental disorder is attested by many instances, both historical and more
      recent, in which the spread or clustering of psychiatric syndromes in populations
      could be related to nutritional deficiency, infectious disease, the presence of
      environmental neurotoxins, the social communication of psychopathology or the
      transmission of abnormal, harmful behaviour patterns within family groups.
      Observations made in clinical practice have repeatedly served as the starting
      point for epidemiological investigation of mental disorders, while conversely
      epidemiological findings have influenced clinical thinking about their
      classification, diagnosis, prognosis and morbid risk. A review of the relevant
      literature underlines the need for a keener awareness of environmental risk
      factors and a fundamentally epidemiological frame of reference in trying to
      grapple with the aetiological problems of mental disorder.

PMID- 8134512
TI  - Statistics and the nature of depression.
AB  - A critical examination is made of the role that statistical methods have played
      in the understanding of depression. The development of instruments for measuring
      depression is illustrated by reference to the Beck Depression Inventory and the
      Hamilton Rating Scale. The controversy over the existence of one or two types of
      depression is examined from the perspective of the statistical tools used. Some
      of the problems in studies of the heritability of depression are outlined. The
      development of clinical trials of depression is examined, with particular
      reference to ECT and maintenance therapy, and the role of meta-analysis is
      discussed.

PMID- 8134514
TI  - Multiple sclerosis presenting as a pure psychiatric disorder.
AB  - Using strict diagnostic criteria, 91 patients with multiple sclerosis (MS) were
      identified in a defined population of 112000. Of these patients, 29 were found to
      have been referred to a psychiatrist at least once. Their psychiatric records
      were searched for cases of MS presenting as a pure psychiatric disorder. Only 18
      of the 30 psychiatric referrals before the diagnosis of MS involved purely mental
      symptoms, and there was no reason to suppose most of them to be related to MS.
      This study highlighted the problem of how to define a true psychiatric
      presentation of MS. The uncovering of two likely candidates among a population
      based sample of 91 supported the existence of such a phenomenon, but it was
      concluded that the only way to ascertain how often purely mental symptoms might
      be the first manifestation of MS would be to conduct a large population-based
      study with controls.

PMID- 8134515
TI  - Assessing the risk of Alzheimer's disease in first-degree relatives of
      Alzheimer's disease cases.
AB  - Family history of Alzheimer's disease (AD) was investigated using a telephone
      reinterview of 99 cases and 116 controls selected from a case-control study of
      170 matched pairs. It was found that the family history method used in the
      initial interview was satisfactory in identifying first-degree relatives and
      assessing their ages of birth and death, but the number of first-degree relatives
      suffering from AD was probably under-estimated. Family history of AD was
      confirmed as a risk factor for AD. Higher estimates of cumulative incidence were
      obtained among case relatives than among control relatives. No evidence was found
      to support the hypothesis that a familial form of AD is more common in those with
      earlier onset AD (before age 75) in those who display early, prominent features
      of aphasia or apraxia, or that an AD gene may be sex-linked. The curves for
      cumulative incidence showed no tendency to reach an asymptote, as is implied by
      the theory that some forms of AD are due to the action of an autosomal dominant
      gene. Estimates of lifetime risk by age 90 were within the range found by other
      investigators. Much larger samples of the very old are needed to obtain estimates
      of total lifetime risk with smaller standard errors.

PMID- 8134516
TI  - Generating and testing a causal explanation of the gender difference in age at
      first onset of schizophrenia.
AB  - Motivated by the lack of knowledge of the pathophysiological processes underlying
      the manifestation of symptoms in schizophrenia, we have worked out a systematic
      search strategy. Since epidemiological distribution patterns consistently
      deviating from expected values provide valuable indications of causal
      relationships, we chose the higher age of females at first admission for
      schizophrenia, first reported by Kraepelin and since then confirmed in over 50
      studies, as the basis for our study. This unexplained epidemiological finding was
      replicated on Danish and Mannheim case-register data by systematically
      controlling for selection and diagnostic artefacts and by testing alternative
      explanations at the individual stage of the study. To check whether the
      difference in age at first admission was determined by a difference in age at
      onset, a representative sample of 267 first-admitted patients with non-affective
      functional psychosis was examined by using an interview for the retrospective
      assessment of the onset of schizophrenia (IRAOS) designed for this purpose. Any
      of the definitions of first-ever onset applied--first sign of mental disorder,
      first psychotic symptom, first acute episode--led to a significant age difference
      of 3.2 to 4.1 years between the sexes. The distribution of onsets across the life
      cycle showed a later increase and a second, lower peak between the ages of 45 and
      54 years among females compared with males. The lifetime risk for schizophrenia
      was equal for males and females. After testing the plausibility of psychosocial
      versus biological explanations we hypothesized that due to the effect of
      oestrogens the vulnerability threshold for schizophrenia is elevated in females
      until the menopause. Animal experiments and post mortem analyses showed that
      chronic oestrogen applications significantly shortened dopamine-induced behaviour
      and reduced D2 receptor sensitivity in the brain. The applicability of this
      pathophysiological mechanism to human schizophrenia was tested on acutely
      schizophrenic females with normal menstrual cycles. A significant negative
      correlation was found between measures of symptomatology and plasma oestrogen
      levels. The manifestation of symptoms in schizophrenia appears to be influenced
      by a sufficiently sensitive D2 receptor system in the brain, blocked by
      neuroleptics and modulated by oestrogens.

PMID- 8134517
TI  - Gender and mortality in schizophrenia: do women act like men?
AB  - The effect of gender on mortality was explored for a sample of DSM-III diagnosed
      schizophrenics followed for up to 42 years. The data for 332 cases and 304
      matched normal controls were from the retrospective cohort family studies, the
      Iowa 500 and non-500. Survival analysis and Cox regression models were used to
      test the effects of gender, illness status and their interaction on the risks for
      natural and unnatural deaths. The control men experienced significantly more
      unnatural deaths than the control women, which was not found for schizophrenic
      men and women. The unnatural death rate among schizophrenic women was similar to
      the rate for schizophrenic and control men, and significantly higher than for
      control women during the early phase of the illness. Findings suggest that some
      factors that predict suicide may be similar for schizophrenic women and men.

PMID- 8134518
TI  - Sex differences in minor psychiatric morbidity among three aboriginal groups in
      Taiwan: the effects of lineage.
AB  - Sex differences in minor psychiatric morbidity (MPM) have been investigated among
      three aboriginal groups in Taiwan. The study included both ethnographic
      observation and a sample survey (N = 733) using a modified Clinical Interview
      Schedule. The findings lend support to the hypothesis that although a female
      excess of MPM will be found among the patrilineal group (the Bunun), the reverse
      will be observed in the matrilineal group (the Ami); no such difference will be
      found in the bilateral group (the Atayal). Further analysis revealed sex
      differences in the mean duration of MPM and similar incidence ratios between two
      sexes in these three groups. Possible sociocultural explanations are proposed.

PMID- 8134519
TI  - Anhedonia: a neglected symptom of psychopathology.
AB  - In the last century psychopathologists attached importance to the concept of
      anhedonia, the loss of ability to experience pleasure. Its role in the diagnosis
      of melancholia was considered to be crucial. In the present century attention to
      anhedonia has faded, possibly because of the focus upon depressed mood as the
      pathognomonic feature of depressive disorders. Research on the symptomatology of
      endogenous depression did not include the concept; anhedonia was also lacking
      from the major instruments of psychiatric research, the depression rating scales,
      Attention was drawn to anhedonia by two authors: by Meehl in the 1960s and by
      Klein in the 1970s. Meehl considered anhedonia from the point of view of a
      personality defect predisposing to mental illness; and Klein regarded anhedonia
      to be a symptom of depressive illness and probably the best clinical marker
      predicting response to antidepressant drugs. In 1980 the revised DSM presented
      the concept of 'loss of interest or pleasure' as one of the two cardinal symptoms
      of major depression. Since then there has been a gradual recovery of emphasis
      although many systems confuse the two concepts of 'loss of interest' and
      anhedonia. It is possible that anhedonia may provide the key to a more exact
      delineation of depressive disorders in biological research and in clinical
      practice. Further research will depend upon a more precise, cross-nationally
      agreed definition of the concept and the means of its assessment.

PMID- 8134520
TI  - Psychological and social correlates of the onset of affective disorders among
      pregnant women.
AB  - One hundred and twenty women recruited from attenders at the antenatal clinic of
      the Obstetrics Department of a general hospital were asked to complete ad hoc
      questionnaires during pregnancy; they were then interviewed by psychiatrists
      using a structured diagnostic interview, the Schedule for Affective Disorders and
      Schizophrenia (SADS). Nineteen (16%) women were identified as having an onset of
      an affective disorder during the period of pregnancy, mainly (68%) during the
      first trimester. As compared with the women without any such onset (controls),
      the women with pregnancy-related affective disorder (PRAD) were characterized by
      (1) it being their first pregnancy or first delivery with past termination of
      pregnancy, (2) early loss of either parent by death, (3) high Eysenck Personality
      Questionnaire (EPQ) Neuroticism (N) and Psychoticism (P) scores, (4) living in a
      flat with either a plan to stay there after the forthcoming childbirth or an
      expectation that their accommodation would be crowded, and (5) negative response
      to the news of the pregnancy by the husband with low intimacy. The effects of
      these factors were additive since the probability of developing a PRAD episode
      was highly correlated with the number of factors reported.

PMID- 8134521
TI  - Road traffic noise, noise sensitivity and psychological disorder.
AB  - The relationship between traffic noise exposure and psychological morbidity was
      assessed using the population-based Caerphilly Collaborative Survey of 2398 men
      from Caerphilly, South Wales. The findings showed that traffic noise exposure
      levels were strongly associated with annoyance to noise. Noise-sensitive men were
      more likely to be highly annoyed by noise exposure than less noise-sensitive men.
      There was no direct association between noise exposure level and psychological
      morbidity but there were provocative interactions with noise sensitivity. The
      role of noise sensitivity is discussed as an indicator of vulnerability to
      environmental stressors and a measure of negative affectivity and over-reporting.

PMID- 8134522
TI  - Chronic fatigue in primary care attenders.
AB  - From 686 patients attending primary care physicians, 77 were identified by a
      screening procedure as having chronic fatigue. Of these, 65 were given a
      comprehensive psychological, social and physical evaluation. Seventeen cases
      (26%) met criteria for the chronic fatigue syndrome. Forty-seven (72%) received
      an ICD-9 diagnosis of whom 23 had neurotic depression, with a further 5 meeting
      criteria for neurasthenia. Forty-nine were 'cases' as defined by the revised
      Clinical Interview Schedule (CIS-R), and 42 if the fatigue item was excluded.
      Psychiatric morbidity was more related to levels of social stresses than was
      severity of fatigue. The main difference between these subjects and those
      examined in hospital settings is that the former are less liable to attribute
      their symptoms to wholly physical causes, including viruses, as opposed to social
      or psychological factors. Identification and management of persistent fatigue in
      primary care may prevent the secondary disabilities seen in patients with chronic
      fatigue syndromes.

PMID- 8134523
TI  - Fat phobic and non-fat phobic anorexia nervosa: a comparative study of 70 Chinese
      patients in Hong Kong.
AB  - A mixed retrospective-prospective study of 70 Chinese anorexic patients in Hong
      Kong shows that although they were similar to Western anorexics in most other
      ways, 41 (58.6%) of them did not exhibit any fear of fatness throughout their
      course of illness. Instead, these non-fat phobic patients used epigastric
      bloating (31.4%), no appetite/hunger (15.7%) or simply eating less (12.9%) as
      legitimating rationales for food refusal and emaciation. Compared to fat phobic
      anorexics, they were significantly slimmer pre-morbidly (P < 0.0001) and were
      less likely to exhibit bulimia (P = 0.001). The possible explanations for the
      absence of fat phobia and the interpretive dilemma this provokes are discussed
      from historical, pathoplastic and cultural anthropological perspectives. It is
      argued that anorexia nervosa may display phenomenological plurality in a
      Westernizing society, and its identity may be conceptualized without invoking the
      explanatory construct of fat phobia exclusively. As non-fat phobic anorexia
      nervosa displays no culturally peculiar features, it is not strictly speaking a
      Western culture-bound syndrome, but may evolve into its contemporary fat phobic
      vogue under the permeative impact of Westernization. Its careful evaluation may
      help clarify the aetiology and historical transformation of eating disorder,
      foster the development of a cross-culturally valid taxonomy of morbid states of
      self-starvation, and exemplify some of the crucial issues that need to be tackled
      in the cross-cultural study of mental disorders.

PMID- 8134524
TI  - Guidelines for the diagnosis and treatment of depression for primary care
      physicians. Implications for consultation-liaison psychiatrists.

PMID- 8134525
TI  - Psychiatric and psychosocial aspects of bone marrow transplantation.
AB  - Bone marrow transplantation (BMT) is being increasingly used to treat children
      and adults with a variety of life-threatening diseases. Although BMT is a life
      saving intervention in many instances, it is a high-technology procedure--both
      aggressive and life-threatening--associated with an array of physical and
      psychological stressors. Therefore, psychiatric and psychosocial research and
      intervention can greatly contribute to the understanding and management of BMT
      recipients, donors, and their families. Seven major areas of psychiatric and
      psychosocial concern in BMT are identified and the literature relevant to each
      area is reviewed.

PMID- 8134526
TI  - The psychology of factitious disorders. A reconsideration.
AB  - Factitious disorder (FD) is a form of somatization that involves apparent
      deception, simulation of illness, and imposture. This deception may be
      distinguished from other forms of lying in that patients with FD may suffer from
      underlying disturbances in the sense of reality and in reality testing. These
      features may be associated with a poorly consolidated sense of self and with
      difficulty regarding emotional experience as real. Factitious behavior may serve
      to stabilize the sense of self by concretizing and legitimizing the subjective
      experience of distress and by evoking responsiveness of a care-giver in a
      relatively safe, structured context. A psychotherapeutic stance focused on
      identifying and validating the patient's subjective experience may lead to a
      reduction in factitious behavior and to a more authentic and stable sense of
      self, in which emotional as well as physical experience is regarded as real.
      However, most patients with FD refuse treatment. Further, psychosis and
      suicidality are complications that may occur during the course of psychotherapy.

PMID- 8134527
TI  - Bipolar disorder associated with Klinefelter's syndrome and other chromosomal
      abnormalities.
AB  - A patient with bipolar disorder and previously undiagnosed Klinefelter's syndrome
      presented with acute mania refractory to pharmacotherapy and was successfully
      treated with electroconvulsive therapy. This case constitutes the 31st case
      report documenting the coexistence of bipolar disorder with chromosomal anomalies
      and the 14th such patient with Klinefelter's syndrome. The relevance of this case
      to understanding the genetics of bipolar disorder is explored through a review of
      previously published reports of bipolar patients with chromosomal abnormalities.
      The relatively high incidence of Klinefelter's syndrome among this group of
      patients is discussed in the context of evidence for linkage of bipolar illness
      to the X chromosome.

PMID- 8134528
TI  - Eating and psychiatric symptoms as a function of Axis II comorbidity in bulimic
      patients. Three-month and six-month response after therapy.
AB  - Using DSM-III-R criteria, the authors organized 61 bulimic patients into
      "Borderline," "Other Personality Disorder," and "No Personality Disorder" groups,
      and then examined eating and comorbid symptoms at 3-month intervals during 6
      months of multimodal therapy. Personality-disorder classifications seemed to
      predict neither the severity nor responsiveness to treatment of bulimic symptoms;
      all groups showed reliable and clinically significant improvements in eating
      habits over time. Conversely, the borderline patients showed reliably more
      comorbid symptoms than did any other group; their scores on disorder-specific
      dimensions--like borderline "traits" and maladaptive defenses--remained
      distinctly elevated throughout treatment. Our findings indicate that 1) a
      "borderline/nonborderline" distinction predicts temporally stable--and
      theoretically meaningful--differences in comorbid profiles, and 2) there exists
      an intriguing degree of independence, at least during ongoing treatment, between
      severity of character pathology and degree of change obtained on eating symptoms.
      Theoretical and clinical implications are discussed.

PMID- 8134529
TI  - Factors determining the level of anxiety state in geriatric primary care patients
      in a community dwelling.
AB  - The authors examined the association between anxiety state and various
      sociodemographic factors, as well as measures of general health, mood, and stress
      in a community-dwelling, geriatric population. A survey questionnaire designed
      for the study was completed by 123 randomly selected subjects. Univariable linear
      regression analysis showed anxiety state to have an inverse association with age
      (beta = -0.29, P = 0.0001) and general health measures (P = 0.0001), and to have
      a direct relationship with depression (beta = 0.78, P = 0.0001), life stress
      events (beta = 0.98, P = 0.01), and medical comorbidity (beta = 1.04, P = 0.01).
      Gender differences in anxiety state were not found. The results provide a
      framework to begin understanding those factors that contribute to anxiety states
      in late life. This study revealed anxiety and depression to be highly correlated
      even in elderly subjects who reported low levels of anxiety and depressive
      symptoms.

PMID- 8134530
TI  - Characteristics of HIV-infected patients in an inpatient psychiatric setting.
AB  - Psychiatric admissions of patients infected with the human immunodeficiency virus
      (HIV) over a 5-year period (1986-1991) are reviewed. Ninety-one patients were
      studied. Suicidal thoughts/attempt was the most common reason for hospital
      admission. The two most common diagnostic categories were 1) organic mental
      syndrome, and 2) substance abuse/dependence. Forty-five percent of the patients
      either initiated their discharges or drastically improved without the use of
      psychotropic medications. The authors suggest that outpatient psychiatric
      facilities can provide psychiatric care for HIV-infected patients seeking it.

PMID- 8134531
TI  - Late-onset psychosis with somatic delusions.
AB  - The authors studied 10 patients who had late-onset psychosis with somatic
      delusions and 2 comparison groups similar in age and education: 9 late-onset
      psychosis patients without somatic delusions and 10 normal control subjects.
      Demographic, clinical, and neuropsychological data were obtained. Brain magnetic
      resonance imaging was also done and compared. The patients with somatic delusions
      were somewhat more likely to be women, have been ill longer, and meet DSM-III-R
      criteria for delusional disorder, compared with late-onset psychotic patients
      without somatic delusions. Patients with somatic delusions also had lower scores
      on a full-scale IQ test, compared with the normal comparison subjects. The
      patients with somatic delusions rarely benefitted from and poorly complied with
      treatment with psychotropics. The study's limitations, such as small sample size
      and heterogeneity of diagnosis, as well as the possible clinical implications of
      these findings are also discussed.

PMID- 8134532
TI  - A model for managing clinical and personnel issues in C-L psychiatry. The
      Department of Pediatric Psychiatry at Children's Hospital at Stanford.

PMID- 8134533
TI  - Dextroamphetamine treatment for depression in terminally ill patients.

PMID- 8134534
TI  - Dissociation precipitated by propranolol.

PMID- 8134535
TI  - Psychological resolution of a supraventricular tachycardia.

PMID- 8134536
TI  - Delirium at therapeutic serum concentrations of digoxin and quinidine.

PMID- 8134537
TI  - Failla Memorial Lecture. The prevalence of multilocus lesions in radiation
      induced mutants.
AB  - In L5178Y mouse lymphoblasts, ionizing radiation-induced mutant frequencies were
      dramatically higher when the genetic marker analyzed was heterozygous (tk+/tk-)
      than when hemizygous (tk+/tk0 or hprt+/hprt0). In contrast, base-change mutagens
      induced similar mutant frequencies at heterozygous and hemizygous loci. These
      results indicate that the majority of radiation-induced mutants harbor multilocus
      lesions, and that these mutants are poorly recovered when the target gene is in a
      hemizygous chromosomal region. Dose-rate dependence of radiation-induced mutant
      frequency was demonstrated at the heterozygous tk locus but not at the hemizygous
      hprt locus; in a cell line deficient in the rejoining of DNA double-strand breaks
      (DSBs), no dose-rate dependence was observed for either locus. The majority of TK
      /- mutants, whether spontaneous or induced by X, alpha-particle or UV radiation,
      or by photosensitization, showed loss of the entire active tk allele. The
      percentage of TK-/- mutants exhibiting inactivation of galactokinase, encoded by
      the neighboring gk gene, was high in UV repair-deficient cells exposed to UV
      radiation and in DNA DSB repair-deficient lines exposed to X radiation. Thus the
      presence of unrepaired DNA lesions, whether DSBs or pyrimidine dimers, appears to
      result in an increase in the percentage of mutants harboring multilocus lesions.

PMID- 8134538
TI  - Concentration- and pH-dependent ammonia yields in the reaction of hydrated
      electrons with glycylglycine.
AB  - Competition between recombination of the radicals formed in the gamma radiolysis
      of water (eaq-, OH, H) and the reaction of eaq- with glycylglycine is
      investigated in glycylglycine solutions of various concentrations and pH. First,
      the concentration dependence of the ammonia yields is measured in the
      glycylglycine solutions of between 0.5 mM and 1.0 M. The G values of ammonia
      appear to reach a plateau of 2.47 +/- 0.05 molecules/100 eV at the low
      concentrations (1-5 mM) and increase to 3.81 +/- 0.07 molecules/100 eV at the
      high concentration (1 M). Secondly, the pH dependence of the ammonia yields is
      measured at low (1 and 5 mM) and high (0.1 and 0.2 M) concentrations of
      glyclyglycine. For concentrated glyclyglycine solutions, the ammonia yields
      increase with increasing pH, as expected based on comparison of the probabilities
      of the competitive reactions. However, the G values of ammonia reach a maximum at
      pH 9.0 and then decrease as the pH increases for dilute solutions. The lower G
      values at higher pH for dilute glycylglycine solutions may result from increased
      interspur recombination since the rate constant for the reaction of eaq- with
      glycylglycine is decreased and, as a consequence, the scavenging capacity of
      glycylglycine for eaq- decreases approximately 4.7-fold from low to high pH.

PMID- 8134539
TI  - Energy deposition and ionization fluctuations induced by ions in small sites--an
      analytical approach.
AB  - A concise, analytical approach is developed for calculating energy deposition and
      ionization fluctuations in volumes within ion-irradiated media which have
      dimensions as small as 1 nm. The method accounts for both direct ion interactions
      with the site and interactions of secondary electrons which are produced by ions
      in the surrounding medium. Particular attention is given to the way the
      contributions of the two types of events are combined. Since energy deposition
      fluctuations are simply related to the fundamental quantities ZD and yD employed
      in microdosimetry theory, this new approach provides a convenient means to obtain
      these parameters. Results obtained with the analytical method show good agreement
      with Monte Carlo charged-particle track-structure calculations of yD for 0.5 to
      20 MeV protons incident on spherical sites of water vapor with diameters ranging
      from 1 nm to 10 microns. In contrast to Monte Carlo techniques, the analytical
      method does not depend on knowing the intricacies of single ion and electron
      interactions with the target and can therefore be adapted to calculations with
      heavier incident ions and different target materials, including those of the
      condensed state.

PMID- 8134540
TI  - Reduced recovery of translocations from X-irradiated spermatogonial stem cells of
      dominant spotting (Wv/+) and steel (Slcon/Slcon) mice.
AB  - Dose-response relationships for X-ray-induced reciprocal translocations in
      spermatogonial stem cells of mutant and wild-type mice were established by
      spermatocyte analysis many cell generations after irradiation. The mutants
      studied were Wv/+, the viable allele of dominant spotting in the heterozygous
      state, and Slcon/Slcon, the homozygous contrasted allele of steel. The results
      show that the recovered yield of translocations was lowered in both mutants with
      steel being most extreme. Remarkably, however, no indications for enhanced cell
      killing were obtained in the mutants, and consequently the peak yields of
      translocations occurred at about the same dose level (6 Gy) as in normal mice.
      Histological analysis suggested that the postirradiation recovery of the germinal
      epithelium was retarded in the mutants with the effect in the steel mice again
      being most extreme. These differences in differentiation-multiplication patterns
      of regenerating spermatogonia after irradiation are probably responsible for the
      reduced recovery of translocations from the mutant mice.

PMID- 8134541
TI  - Radiation-induced cell cycle delay measured in two mouse tumors in vivo using
      bromodeoxyuridine.
AB  - The magnitude of the delay of cells in the phases of the cell cycle after
      irradiation may be related to the radioresponsiveness of tumor cell populations.
      In this study we have quantified division delay in two mouse tumors in vivo after
      single and fractionated doses of X rays and single doses of neutrons. The
      incorporation of bromodeoxyuridine and flow cytometry provided a sensitive and
      quantitative method to detect cell cycle perturbations after radiation treatment.
      The more rapidly growing SAF tumor showed less G2-phase delay per gray than a
      more slowly proliferating tumor, the Rh (0.9 vs 1.8 h). In addition, the SAF
      tumor failed to show any G1/S-phase delay while the Rh tumor experienced a longer
      G1-phase delay than that measured for G2 phase (3.1 vs 1.8 h). There was a trend
      in both tumors for lower doses to be more effective in producing cell cycle
      delays. Neutrons caused longer G2-phase delays on a unit dose basis, 2.5 and 5.4
      h for the SAF and Rh tumors, respectively. The RBE for neutrons for division
      delay was found to be 2.9 and 2.8 for the SAF and Rh tumors, while the RBE for
      growth delay was 3.4 and 3.5. Fractionation of the X-ray dose caused a reduction
      in division delay at higher total doses (10 or 12 Gy) but was without effect at
      the lower dose studied (6 Gy). These studies show the feasibility of measuring
      cell cycle delays in vivo, and future developments are suggested for a possible
      predictive test in patients receiving radiotherapy.

PMID- 8134542
TI  - Regulation of heat and radiation stress responses in yeast by hsp-104.
AB  - We have investigated the role of heat-shock protein 104 (hsp-104) in the
      induction of ionizing radiation resistance in yeast. Yeast defective in the
      production of hsp-104 are constitutively sensitive to killing by heat and are
      known to be compromised for the induction of thermotolerance. We confirmed that
      hsp104 yeast mutants are altered in their ability to become thermotolerant by a
      heat stress. However, we found that the mutant strain did respond to heat shock
      and increased its resistance to a second lethal heat stress, although the
      magnitude of the increase was much lower than for the parental wild-type strain.
      Here we report that the constitutive level of ionizing radiation resistance was
      higher in the hsp104 mutant compared to wild-type cells and that heat shock
      induced increased radioresistance in both strains. When radiation was used as the
      stressing agent, thermal resistance was fully induced in wild-type cells and only
      slightly induced in the hsp104 mutant. In comparison, radioresistance was induced
      in both cell strains by a radiation stress. The increased radiation resistance
      was always slightly higher in the hsp104 mutant but developed with similar
      kinetics in both cell strains. Entry into stationary growth phase is another
      event known to induce both thermal tolerance and radiation resistance in yeast.
      In these experiments, entry into stationary phase induced similar levels of
      thermal tolerance in the two strains but higher levels of radioresistance in
      hsp104 mutants. The activation of both resistance mechanisms occurred earlier in
      the hsp104 mutants compared to wild-type cells. These results show that hsp-104
      is not essential for either the process by which the cell recognizes and responds
      to any of these stresses, or the mechanisms by which the cell actually elevates
      its resistance to heat and radiation. We conclude, however, that hsp-104 is
      important in regulating the development and magnitude of induced radiation
      resistance as well as induced thermal tolerance in yeast.

PMID- 8134543
TI  - Visible-light and X irradiations of Chinese hamster lung cells treated with
      hematoporphyrin derivative.
AB  - Single cell suspensions of Chinese hamster lung cells were treated with
      hematoporphyrin derivative (HPD) and were exposed under aerobic conditions to
      visible light alone, X rays alone or light and X rays concurrently. Cytotoxicity
      was assayed using the colony formation ability of cells as the end point. The
      drug toxicity, phototoxicity, radiosensitization and photoradiosensitization of
      HPD were examined for a drug concentration of 1 microgram/ml and incubation time
      of 24 h. In these experiments, the X-ray dose was 3 Gy and the energy fluence of
      visible light was 0.35 kJ/m2, and both irradiations lasted for 10 min. A
      significant enhancement in cytotoxicity was observed when the HPD-treated cells
      were irradiated concurrently with light and X rays. However, no significant
      enhancement was observed when visible-light and X irradiations were performed
      sequentially with a 15-min waiting time between the two irradiations.

PMID- 8134544
TI  - Ionizing radiation enhances platelet adhesion to the extracellular matrix of
      human endothelial cells by an increase in the release of von Willebrand factor.
AB  - The effect of radiation on the secretion of von Willebrand factor by endothelial
      cells was studied in a three-compartment culture system. The release of von
      Willebrand factor was significantly increased at 48 h after a single gamma
      radiation dose of 20 Gy in both the luminal and abluminal direction by 23 (P <
      0.05) and 41% (P < 0.02), respectively. To establish whether the enhanced
      production of von Willebrand factor affected the thrombogenicity of the
      extracellular matrix, platelet adhesion to the matrix produced by a monolayer of
      cultured endothelial cells during 48 h after irradiation was analyzed in a
      perfusion chamber at high shear rate (1300 s-1). Platelet adhesion was
      significantly increased by irradiation both in the presence and in the absence of
      plasmatic von Willebrand factor by 65 (P < 0.05) and 34.5% (P < 0.005),
      respectively. Incubation of the perfusate with a monoclonal antibody that blocks
      the binding of von Willebrand factor to platelet GPIb (CLB-RAg 35) resulted in an
      almost complete inhibition of platelet adhesion. These data indicate that
      radiation enhances platelet adhesion to the the extracellular matrix by an
      increase in the release of von Willebrand factor by endothelial cells. This event
      may be important in early radiation-induced vascular pathology.

PMID- 8134545
TI  - A mortality kinetics approach to characterizing the relative biological
      effectiveness of short-term exposure to fission neutrons.
AB  - A Gompertz age-specific mortality rate model was developed for toxicity resulting
      from a short-term exposure to a toxicant resulting in nonrepaired injury that
      summates with natural (aging) injury. The model was applied to mortality data for
      male and female B6CF1 mice subjected to 60 weekly whole-body exposures to fission
      neutrons and gamma rays (W. F. Thomson and D. Grahn, Radiat. Res. 115, 347-360,
      1988). There was no apparent increase in the age-specific mortality rate of mice
      during the 60-week period of fractionated exposures to fission neutrons.
      Cumulative toxicity was not exhibited in the Gompertz functions of mice exposed
      to fission neutrons until after termination of exposure. As a secondary issue,
      the Gompertz age-specific mortality rate model was modified to incorporate
      paradoxical "oversurvival" or longevity hormesis in mice exposed to fission
      neutrons. This modified model was compared to a model that has no allowance for
      oversurvival. The logarithmic-logistic function was used to relate the parallel
      upward displacement of the Gompertz function at steady state (i.e., the time
      after exposure ceased and the mortality effects of oversurvival dissipated) with
      dose. The data were shown to support the assumption of parallel upward
      displacement. The relative biological effectiveness (RBE) of fission neutrons
      compared to gamma rays was calculated using the steady-state displacement of the
      Gompertz functions. The RBE was defined as the ratio of doses D gamma/DN
      necessary to produce the same upward displacement by neutron radiation (DN) and
      gamma rays (D gamma). This definition is proposed as a useful measurement of RBE
      for studies of short-term exposures to fractionated radiation.

PMID- 8134546
TI  - Comparative effects of neutron irradiation and X irradiation on the embryonic
      development of the rat.
AB  - Our aim was to compare the dose-response relationship for the embryotoxic effects
      of 0.43 MeV neutrons with those of 240 kVp X rays after in utero exposures during
      early organogenesis in the rat. At 9.5 days after conception, pregnant rats were
      exposed to 0.025 to 0.35 Gy 0.43 MeV neutrons at a dose rate of 0.04 to 0.07
      Gy/h. Comparable biological effects were produced using 0.50 to 2.05 Gy 240 kVp X
      rays. Neutron irradiation produced a greater proportion of offspring with very
      low body weight than with malformations when compared to X rays. There were no
      embryotoxic effects observed at neutron exposures of 0.025, 0.049, 0.079, 0.10,
      0.15 and 0.20 Gy or X-ray exposures of 0.50 and 0.96 Gy. Taken together, the
      results suggest that the mechanisms by which neutron irradiation affects
      embryonic development may, in part, be both quantitatively and qualitatively
      different from those by which X irradiation affects development. These results
      support the generalization that the embryo exhibits a nonlinear response to
      increasing doses of ionizing radiations during the period of early organogenesis.

PMID- 8134547
TI  - The effects of X-ray energy and an iodine-based contrast agent on chromosome
      aberrations.
AB  - A study was undertaken to evaluate the effect of combining irradiation with X
      rays of various energies and an iodine-based contrast agent on the induction of
      chromosome aberrations in the peripheral lymphocytes of blood samples taken from
      healthy young donors. Although no enhancement of the effect of radiation was
      induced when blood samples with the iodine-based contrast agent were given 35 kV
      X irradiation, an 80 kV X-ray exposure induced an enhanced level of chromosome
      aberrations, and at 250 kV X irradiation, an enhancement of the frequencies of
      chromosome aberrations was seen in blood samples with the iodine-based contrast
      agent, especially when a Lucite phantom was employed in studies to increase the
      scattered rays. It was thus shown by microdosimetric analysis that X irradiation
      combined with an iodine-based contrast agent causes an enhancement of the
      absorbed radiation dose, which is dependent on the X-ray energies employed. This
      phenomenon may have clinical use in the radiotherapeutic management of tumors,
      although further extensive studies of tumor vascularity must be pursued before
      this can be applied clinically.

PMID- 8134548
TI  - Polonium metabolism in adult female baboons.
AB  - The biokinetics of polonium in nonhuman primates (Papio anubis) has been studied
      after intravenous injection of 210Po citrate. The urinary excretion of polonium
      in the baboon could be described by a single exponential function with a half
      time of 15.6 days. Excretion fractions of polonium were found to be markedly
      different from those reported for other species, including humans. Polonium-210
      was found to be distributed throughout the soft tissues of the baboon with 29% of
      the injected polonium being deposited in liver, 7% in kidneys and 0.6% in spleen.
      Retention of polonium in all tissues exhibited single exponential functions;
      however, the biological half-times were variable, ranging from 15 to 50 days.

PMID- 8134549
TI  - Patterns of lung cancer mortality among uranium miners in West Bohemia with
      varying rates of exposure to radon and its progeny.
AB  - Lung cancer mortality in a cohort of 4320 miners first employed during 1948-1959
      at the Jachymov and Horni Slavkov uranium mines in West Bohemia and followed
      until 1 January 1991 has been studied to gain a greater understanding of the
      consequences of exposure to radon and its progeny. Among men whose exposure rates
      never exceeded 10 working levels, excess relative risks per unit exposure were
      greater in younger men, and exposures received in the periods 15-24, 25-34 and
      35+ years previously were found to have 47, 24 and 0% of the effect of exposures
      5-14 years previously. Within this low-exposure-rate group excess relative risk
      increased linearly with time-weighted cumulative exposure and did not depend on
      exposure rate or duration of exposure. For men who spent less than 20% of their
      employment at the Jachymov mine the excess relative risk per working level month
      was 1.36% (95% confidence interval 0.52-3.54) in the baseline category (age group
      55+ and exposure received 5-14 years previously). For men who spent more than 20%
      of their employment at Jachymov, the corresponding excess relative risk per
      working level month was higher by a factor of 1.80 (95% confidence interval 1.27
      2.97). The difference may be due to the fact that men who spent more than 20% of
      their employment at Jachymov were exposed to the much higher levels of arsenic in
      the dust at the Jachymov mine than at other mines. When men with exposure rates
      above 10 working levels were included in the analysis, patterns of risk were
      complex and depended on both exposure rate and duration of exposure in addition
      to the factors mentioned above. If these findings are confirmed elsewhere,
      calculation of risk estimates for extrapolation to modern occupational or
      environmental exposures should be based on miners with exposure rates below about
      10 working levels. Further investigation is desirable of the influence of dusts
      containing arsenic on lung cancer risk in miners exposed to radon.

PMID- 8134550
TI  - Primary liver tumors among Danish patients exposed to Thorotrast.
AB  - The potential carcinogenic effects of internally deposited alpha-particle
      emitting nuclides, notably plutonium, in the liver in humans are unknown but are
      of concern in relation to exposures from the nuclear industry. However, patients
      injected with the radiographic contrast medium Thorotrast are chronically exposed
      to alpha-particle radiation from 232ThO2 in the liver. Among 1003 patients
      injected with Thorotrast, 584 of whom were alive 15 years after the injection and
      40 at the end of follow-up, a total of 127 liver cancers were diagnosed, 45 of
      which were hepatocellular carcinomas, 41 cholangiocarcinomas and 33
      hemangiosarcomas. The median time from injection to diagnosis was 35 years (range
      18-48) and the cumulative frequency was 55.4% after 48 years. In univariate and
      multivariate analyses, the cumulative frequency of liver cancer was best
      described as a function of the estimated mean cumulative alpha-particle radiation
      dose to the liver 15 years ago, being independent of age, gender and volume of
      injected Thorotrast. This may be interpreted to mean that the liver cancer rate
      is not related to the dose rate and that the period from malignant transformation
      to diagnosis of cancer is 15 years. The risk of liver carcinogenesis induced by
      alpha-particle radiation, assuming 15 years from induction to diagnosis, was
      estimated to be 712 cases/10(4) persons per gray. This value is considerably
      higher than estimated earlier.

PMID- 8134551
TI  - Imaging of closed head injury.

PMID- 8134552
TI  - Antibiotic-induced diarrhea: specificity of abdominal CT for the diagnosis of
      Clostridium difficile disease.
AB  - PURPOSE: To evaluate the specificity of abdominal computed tomography (CT) in the
      diagnosis of Clostridium difficile disease. MATERIALS AND METHODS: The authors
      retrospectively reviewed CT scans of 64 patients with C difficile disease and 30
      control subjects with diarrhea and negative findings for C difficile disease at
      stool tests. RESULTS: Colon wall thickening (range, 4-22 mm; mean, 11.7 mm;
      median, 11 mm) was seen in 39 patients (61%) with C difficile disease. Other
      findings included focal colon wall thickening (n = 28) and pancolonic thickening
      (n = 11). Two patients had only right-sided and transverse colon involvement. CT
      specific diagnostic features of C difficile disease, such as nodular haustral
      thickening or the accordion pattern, were present in 17% of patients. No colonic
      abnormality was detected in 25 patients (39%). Seven of the 30 (23%) control
      subjects had colon wall thickening. Six of those seven subjects were subsequently
      determined to have ischemic colitis. The sensitivity of CT in the detection of
      colon abnormalities in patients with C difficile disease was 85%, and the
      specificity was 48%. CONCLUSION: Specific CT features of C difficile disease are
      uncommon. A considerable number of patients (39%) with C difficile disease have
      normal abdominal CT scans.

PMID- 8134553
TI  - Hepatic peribiliary cysts: multiple tiny cysts within the larger portal tract,
      hepatic hilum, or both.
AB  - PURPOSE: To describe characteristic imaging features of hepatic peribiliary
      cysts. MATERIALS AND METHODS: Four patients with hepatic cysts in which the
      radiologic (n = 3) or histologic (n = 1) findings were consistent with
      peribiliary cysts of the liver (multiple small cysts seen exclusively in the
      larger portal tract, hepatic hilum, or both at gross examination and dilatations
      of extramural peribiliary gland at histologic examination) underwent computed
      tomography (CT) and ultrasound (US). In three patients, CT was performed after
      drip infusion of cholangiographic contrast material. RESULTS: Contrast material
      enhanced CT clearly depicted many tiny cysts along the larger portal veins up to
      the third- or fourth-order branch (n = 3). US depicted multiple cysts in the
      echogenic portal tract definitely (n = 2) or equivocally (n = 2). On
      cholangiographic contrast-enhanced CT scans, cystic areas were located adjacent
      to or surrounding the bile ducts, and the possibility of biliary dilatation,
      communication, or both was disproved. CONCLUSION: Hepatic peribiliary cysts can
      be diagnosed with US and enhanced CT, especially with CT performed after
      administration of cholangiographic contrast material.

PMID- 8134554
TI  - Hepatic cavernous hemangiomas: lack of enlargement over time.
AB  - PURPOSE: To determine whether change in size is a characteristic of cavernous
      hemangioma of the liver. MATERIALS AND METHODS: Twenty-one focal masses in 21
      patients were diagnosed as cavernous hemangiomas with imaging-guided percutaneous
      fine-needle biopsy performed between 2 weeks and 2 months after initial imaging
      study (computed tomography [CT] or ultrasonography [US]). Follow-up imaging
      examinations (CT, US, or magnetic resonance imaging plus US) were obtained at 5
      84 months in all patients. RESULTS: The cavernous hemangiomas ranged in size from
      1.5 to 13.5 cm. At follow-up imaging, 19 (90%) of 21 lesions had not changed in
      size; the two remaining lesions increased by 1 and 2 cm over 3 and 10 months,
      respectively. CONCLUSION: The size of the majority of cavernous hemangiomas
      remains stable for periods of follow-up ranging from 5 to 84 months. Growth of
      these lesions is not characteristic and, when it occurs, should prompt
      reassessment of the diagnosis.

PMID- 8134555
TI  - Hepatic hemangioma in cirrhotics with portal hypertension: evaluation with Tc-99m
      red blood cell SPECT.
AB  - PURPOSE: To determine whether extensive shunting associated with portal
      hypertension (PH) adversely affects the diagnostic accuracy of technetium-99m red
      blood cell (RBC) single photon emission computed tomography (SPECT) for hepatic
      hemangioma (HH). MATERIALS AND METHODS: Nineteen possible HHs (1.0-11.0 cm in
      diameter) in 15 cirrhotics with PH were studied with RBC SPECT. RESULTS: RBC
      SPECT allowed correct categorization of four HHs (1.5, 2.8, 4.0, and 4.0 cm in
      diameter) and 13 non-HHs (1.5-11.0 cm in diameter). Two small HHs (1.0 and 1.4 cm
      in diameter) were "missed." Sensitivity, specificity, and accuracy were 67%,
      100%, and 89%, respectively. CONCLUSION: Despite abnormal liver blood flow
      dynamics due to portosystemic collateralization, RBC SPECT allows reliable
      identification of HH in cirrhotics with PH. As in noncirrhotics, its major
      limitation is small lesion size.

PMID- 8134556
TI  - Sequential viewing of abdominal CT images at varying rates.
AB  - PURPOSE: To evaluate radiologists' ability to detect abdominal masses during
      sequential viewing of series of computed tomographic (CT) scans at varying rates.
      MATERIALS AND METHODS: Receiver operating characteristic (ROC) analysis was used
      to assess the ability of five experienced radiologists to determine the presence
      or absence of subtle abdominal masses in 29 cases (15 positive, 14 negative)
      while viewing CT scans sequentially at different rates (0.5, 1, 2, 4, 7, and 21
      images per second) and also at reader-selectable rates. RESULTS: Even at
      extremely fast viewing rates (21 images per second), radiologists performed
      significantly better (P < .05) than would be expected by chance alone (average
      area Az under the ROC curve = 0.73 vs 0.5). As the viewing rate decreased, their
      performance increased. The reader-selectable mode was better than any fixed-rate
      cine mode (average Az = 0.93). CONCLUSION: Fixed-rate sequential viewing of CT
      images for the primary diagnosis of subtle abdominal masses should be restricted
      to no more than one or two images per second, but the reader-selectable viewing
      mode is preferable to any fixed-rate cine mode.

PMID- 8134557
TI  - Hepatocellular carcinoma: CT and MR features after transcatheter arterial
      embolization and percutaneous ethanol injection.
AB  - PURPOSE: To investigate the reliability of computed tomography (CT) and magnetic
      resonance (MR) imaging in the evaluation of the response of hepatocellular
      carcinoma (HCC) to transcatheter arterial embolization (TAE) followed by
      percutaneous ethanol injection (PEI). MATERIAL AND METHODS: Between January 1991
      and November 1992, 20 patients (15 men and five women, aged 53-73 years [mean,
      64.6 years]) with 31 HCC lesions underwent CT and MR imaging before and after
      treatment with combined TAE and PEI. RESULTS: Twenty-seven tumors, which were
      hypointense on post-treatment T2-weighted images and on gadolinium-enhanced T1
      weighted images, were seen to be necrotic at biopsy. In four cases of incomplete
      necrosis, viable tumor was hyperintense on T2-weighted images and was enhanced
      after administration of contrast material. CT provided a larger spectrum of
      imaging features as a result of the presence of both hyperattenuating areas
      (caused by retention of iodized oil) and hypoattenuating areas (due to ethanol
      induced necrosis). CONCLUSION: CT and MR imaging findings proved useful in the
      evaluation of the response of HCC to combined TAE and PEI.

PMID- 8134558
TI  - In vitro MR imaging of the resected stomach with a 4.7-T superconducting magnet.
AB  - PURPOSE: To study the effects of formalin fixation, signal intensity
      characteristics of the stomach-wall layers, and findings suggestive of cancerous
      invasion to the stomach wall in vitro with magnetic resonance (MR) imaging in
      humans. MATERIALS AND METHODS: MR images of nine specimens of stomach cancer and
      29 normal specimens were obtained at 4.7 T; 26 of the normal specimens were fixed
      in 10% formalin for 2 hours to 187 days before imaging. The field gradient was 10
      G/cm; the spatial resolution, 0.1 mm. RESULTS: The mucosal, submucosal, and
      proper-muscle layers were clearly identifiable. The submucosa of the fresh
      specimens had the lowest signal intensity of all specimens on both T1- and T2
      weighted images (P < .01). No statistical correlation existed between signal
      intensity and duration of fixation. Tumor invasion was detected in seven of eight
      specimens with mucosal invasion, all eight specimens with submucosal invasion,
      and three of six specimens with muscle invasion. CONCLUSION: In vitro MR imaging
      enabled differentiation of all three layers of the stomach wall, detection of the
      cancer, and measurement of the depth of invasion.

PMID- 8134559
TI  - Extension of vessels through hepatic neoplasms: MR and CT findings.
AB  - The undisturbed extension of vessels through an area of abnormal hepatic signal
      intensity on magnetic resonance (MR) images or abnormal attenuation on computed
      tomographic (CT) scans has been used as evidence of benign focal fatty
      infiltration and malignant hepatic neoplasms. Five cases are described in which
      either portal or hepatic veins extended through a hepatic lesion without evidence
      of appreciable mass effect, occlusion, or displacement of the vessels. These
      pathologically proved malignancies included hepatic lymphoma, metastatic
      melanoma, and metastatic adenocarcinoma.

PMID- 8134560
TI  - Right atrial MR imaging studies of cadaveric atrial casts and comparison with
      right and left atrial volumes and function in healthy subjects.
AB  - PURPOSE: To assess magnetic resonance (MR) imaging of the right atrium by
      measuring volumes of right atrial casts and determining right atrial volume
      cycles in healthy subjects. MATERIALS AND METHODS: Fourteen human cadaveric
      atrial casts were imaged and right atrial volumes of eight subjects were measured
      with cardiac-gated cine MR. Volumes were calculated and right and left atrial
      volumes were compared. RESULTS: Measured volumes of right atrial casts correlated
      well (r = .99, P < .001) with true volumes with a small underestimation noted (
      7.2 mL +/- 2.3 [standard deviation], P < .001). The maximum in vivo right atrial
      volume averaged 77 mL/m2 +/- 11 of body area. The right atrial reservoir and
      conduit functions accounted for, on average, 58% and 19%, respectively, of the
      ventricular stroke volume; the remaining 23% came from atrial contraction. Right
      to-left peak volume ratio averaged 1.41 +/- 0.15 (P < .001), and all volume
      measurements except conduit volumes were statistically significantly larger in
      the right atrium than the left. CONCLUSIONS: MR imaging provides a reliable means
      to study right atrial volumes and phasic function.

PMID- 8134561
TI  - Pulmonary embolism: confirmation with venous duplex US as adjunct to lung
      scanning.
AB  - PURPOSE: To assess the prevalence of deep venous thrombosis with venous duplex
      ultrasonography (US) in patients who underwent radionuclide lung scanning for
      evaluation of clinically suspected pulmonary embolism (PE) and to assess the
      clinical usefulness of this type of US in the selection of patients for
      anticoagulant therapy. MATERIALS AND METHODS: Two hundred eighty-five lung scan
      and duplex US examinations in 267 consecutive patients seen between January 1987
      and June 1990 with clinical evidence of PE (151 men and 134 women, aged 17-98
      years [mean, 57 years]) were retrospectively reviewed. Lung scans were divided
      into four groups: normal, depicting up to 30% probability of PE, indeterminate or
      intermediate probability of PE, and greater than 90% probability of PE. RESULTS:
      Thrombotic disease was confirmed with US in seven (21%) of 33 patients with
      normal lung scans and in 64 (25%) of 252 patients with abnormal lung scans.
      CONCLUSION: Venous duplex Doppler US is a useful adjunct to lung scanning in
      patients with signs and/or symptoms of PE.

PMID- 8134562
TI  - Peripheral vascular disease: evaluation with stepping DSA and conventional screen
      film angiography.
AB  - PURPOSE: To prospectively evaluate stepping digital subtraction angiography (S
      DSA), which enables peripheral digital subtraction angiography (DSA) of both
      lower extremities after one injection of contrast material, in comparison with
      conventional screen-film angiography (SFA) for evaluation of lower-extremity
      vascular disease. MATERIALS AND METHODS: Fifty consecutive patients were
      prospectively examined. Each study was performed without knowledge of the
      findings in the other. Additional stationary DSA images were obtained whenever
      necessary. All studies were individually evaluated for diagnostic adequacy and
      then side by side for vascular opacification, timing of contrast enhancement,
      ease of reading, and overall superiority. RESULTS: The diagnostic adequacy of S
      DSA was not statistically different from that of SFA (P > .30). SFA was
      subjectively considered superior in opacification (P < .003), ease of reading (P
      < .003), and subjective overall superiority (P < .005). S-DSA was superior in
      timing of contrast enhancement (P < .001). CONCLUSION: The advantages of S-DSA
      can be achieved while the diagnostic adequacy of SFA is maintained. However, SFA
      was considered superior in three of four subjective characteristics.

PMID- 8134563
TI  - Gadolinium-enhanced MR aortography.
AB  - PURPOSE: To evaluate the potential for preferential arterial enhancement at
      magnetic resonance (MR) aortography with an intravenous infusion of paramagnetic
      contrast material. MATERIALS AND METHODS: Gadolinium chelates were administered
      intravenously (0.2 mmol/kg) during three-dimensional MR imaging (1.5 T) in 125
      patients (77 male and 48 female patients, aged 4-86 years [mean, 66 years]) with
      suspected aorta or aortic branch vessel disease. RESULTS: Infusion for the
      duration of the MR acquisition resulted in significant preferential arterial
      enhancement without the confounding effects of excessive venous or background
      tissue enhancement (P < 10(-5)). Angiographic or surgical correlation in 48
      patients revealed an 88% sensitivity and a 97% specificity for detection of
      stenoses or occlusions and a 100% sensitivity and a 100% specificity for
      detection of aortic or iliac artery aneurysms. CONCLUSION: Preferential arterial
      enhancement is possible at MR aortography with an intravenous infusion of
      paramagnetic contrast material.

PMID- 8134564
TI  - Image-guided automated core biopsies of the breast, chest, abdomen, and pelvis.
AB  - PURPOSE: A prospective study was undertaken to measure success at obtaining
      definitive histologic diagnoses with an automated biopsy gun technique. MATERIALS
      AND METHODS: Image-directed biopsies (n = 300) were performed between November
      1989 and June 1992 in 288 patients. Biopsy specimens of breast lesions were
      obtained with ultrasound (US) or stereotaxic mammographic guidance. Biopsy
      samples of lesions from other areas of the body were obtained with computed
      tomographic or US guidance. Clinical follow-up and surgical biopsy were used to
      measure diagnostic accuracy. RESULTS: Overall, a definitive diagnosis was reached
      with core specimen biopsy techniques in 95.3% of cases (286 of 300), and all 286
      definitive findings were accurate. CONCLUSION: Because of the success of this
      approach, the adoption of an automated biopsy gun technique that includes
      histologic examination of a core specimen should be considered by all
      radiologists who perform image-guided biopsies.

PMID- 8134565
TI  - Overdilation of the Wallstent to optimize portal decompression during
      transjugular intrahepatic portosystemic shunt placement.
AB  - PURPOSE: To optimize shunt size with overdilation of the Wallstent during
      creation of a transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND
      METHODS: A TIPS was created in 25 patients with variceal bleeding (n = 22) or
      intractable ascites (n = 3). All shunts were created with one or more Wallstents
      that were dilated with an 8- or 10-mm balloon. In 11 patients with inadequate
      portal decompression or persistent filling of varices, shunts were overdilated
      with a 12-mm balloon. RESULTS: Mean portosystemic pressure gradient fell from
      18.0 mm Hg +/- 6.4 (standard deviation) to 6.8 mm Hg +/- 2.8 after shunt
      placement. In 11 patients in which shunts were overdilated, the mean gradient
      fell from 12.7 mm Hg +/- 5.6 after 10-mm dilation to 6.9 mm Hg +/- 2.8 (P = .01)
      after 12-mm dilation. In six, variceal filling occurred after 10-mm dilation but
      diminished or ceased after overdilation. Stent disruption did not occur. New or
      worsened encephalopathy occurred in four of 14 patients with 10-mm and six of 11
      patients with 12-mm shunt dilation and responded to medical therapy in all but
      two. CONCLUSION: Overdilation of the Wallstent during TIPS placement is effective
      and safe in patients with inadequate portal decompression after 10-mm shunt
      dilation.

PMID- 8134566
TI  - Transjugular intrahepatic portosystemic shunt: angiographic follow-up and
      secondary interventions.
AB  - PURPOSE: To evaluate transjugular intrahepatic portosystemic shunt (TIPS)
      placements and secondary interventions. MATERIALS AND METHODS: Thirty shunt
      venograms were obtained in 21 patients with TIPS placement at 6-month intervals
      or if Doppler ultrasound showed an abnormality. RESULTS: Abnormalities in the
      shunt were shown in 24 venograms (80%). Eight occlusions (two early, five late,
      one repeat) and 16 stenoses (nine hepatic vein, six hepatic vein and stent, one
      stent only) were seen. Two patients with shunt abnormalities experienced
      recurrent bleeding. All others had no signs of recurrent portal hypertension.
      Occluded TIPS were recanalized (n = 5) or a new TIPS was placed parallel to the
      occluded one (n = 2). One repeat occlusion was not revised. Fifteen of 16
      stenoses were treated successfully with balloon catheter dilation (n = 8) or
      additional stent placement (n = 7). The mean portal pressure gradient before
      revision was 21 mm Hg +/- 3.8 (standard deviation) and 13 mm Hg +/- 3.6 after
      revision. CONCLUSION: Stenosis and occlusion of TIPS may be common during long
      term follow-up. Regular examinations may demonstrate abnormalities early. An
      abnormality seen on the shunt venogram usually can be revised during the same
      procedure.

PMID- 8134567
TI  - Intracranial aneurysm in adult polycystic kidney disease: is screening with MR
      angiography indicated?

PMID- 8134568
TI  - Intestinal varices: treatment with the transjugular intrahepatic portosystemic
      shunt.
AB  - PURPOSE: To perform a retrospective evaluation of transjugular intrahepatic
      portosystemic shunt (TIPS) placement for treatment of intestinal varices.
      MATERIALS AND METHODS: TIPS were placed in nine patients (six women and three
      men, aged 36-85 years [mean, 64 years]) with small- (n = 6) and large- (n = 3)
      intestinal varices. Six patients were actively bleeding at the time of shunt
      placement. One patient with colon cancer underwent prophylactic TIPS placement
      for variceal decompression before colectomy. RESULTS: The mean preprocedure
      portosystemic gradient of 26.8 mm Hg +/- 5.1 was reduced to 8.8 mm Hg +/- 2.9.
      Bleeding was controlled in all but one case, in which supplemental variceal
      embolization was required. Two patients died within 5 days of TIPS placement of
      preexisting multisystem failure. Three patients died of unrelated causes at 2, 6,
      and 7 months. The remaining patients were alive an average of 15 months after
      TIPS placement. There was no recurrent bleeding in any case. CONCLUSION: TIPS
      placement is an effective method of decompressing intestinal varices.

PMID- 8134569
TI  - Hemodynamic changes after transcatheter arterial embolization of hepatocellular
      carcinomas.
AB  - PURPOSE: To evaluate the serial hemodynamic changes that occur after
      transcatheter arterial embolization (TAE) of hepatocellular carcinomas (HCCs).
      MATERIALS AND METHODS: Twenty patients with HCCs treated with TAE were evaluated
      with color and duplex Doppler sonography before, immediately after, and 2 days
      after TAE. The changes in hepatic artery and portal vein velocity and flow were
      evaluated. RESULTS: The portal venous velocity and flow did not change
      significantly after TAE. The peak systolic velocity in the proximal hepatic
      artery decreased significantly (P < .01) immediately after TAE then returned to
      baseline values 2 days after TAE; the resistance index of the proximal hepatic
      artery increased significantly (P < .01) immediately after embolization, then
      returned to baseline values 2 days after TAE. Arterial signal in the distal
      hepatic artery, generally absent immediately after TAE, could be recorded 2 days
      after. CONCLUSION: There is a rapidly reversible decrease in hepatic arterial
      flow induced by embolization, without any change in portal venous flow.

PMID- 8134570
TI  - Lunotriquetral interosseous ligament of the wrist: MR appearances in asymptomatic
      volunteers and arthrographically normal wrists.
AB  - PURPOSE: To determine whether the carpal lunotriquetral ligament (LTL) can be
      consistently seen and to establish the normal range of LTL appearances at
      magnetic resonance (MR) imaging as a basis for comparison with LTL tears.
      MATERIALS AND METHODS: MR imaging was used to identify and characterize the LTL
      in 75 wrists with normal LTLs (54 in 27 asymptomatic volunteers, 21 in patients
      with normal arthrograms). RESULTS: The LTL was identified in all wrists and was
      linear in 63% and delta-shaped in 35%. The LTL had homogeneous low signal
      intensity in 73% and linear intermediate signal intensity traversing all or part
      of the LTL in 25%. Fluid signal intensity traversed the LTL in only one wrist. MR
      appearance of the osseous insertion sites varied. Distribution of hyaline
      cartilage signal was related to location within the LTL. CONCLUSION: The LTL can
      be consistently identified at MR imaging, but its appearance varies, which must
      be appreciated when evaluating wrists with suspected LTL tears.

PMID- 8134571
TI  - Distal biceps tendon injury: MR imaging diagnosis.
AB  - PURPOSE: To review the authors' experience with magnetic resonance (MR) imaging
      of patients with suspected injury of the distal biceps tendon. MATERIALS AND
      METHODS: Twenty-one patients with clinically suspected injury of the distal
      biceps tendon were evaluated with MR imaging. Surgical correlation was performed
      in 15 patients, and long-term clinical follow-up was performed in the remaining
      six cases. RESULTS: Twelve complete biceps tears, four partial tears, one
      brachialis rupture, and one ganglion were identified. Axial MR images were more
      valuable than sagittal images in accurately grading distal biceps tendon injury
      preoperatively. There was 100% agreement between MR imaging and surgical
      findings. MR imaging findings led to changes in clinical treatment plans in eight
      patients (38%). CONCLUSION: MR imaging is useful in the evaluation of patients
      with suspected distal biceps tendon injury. In particular, axial MR images of the
      distal biceps insertion are important for accurate grading of the injury.

PMID- 8134572
TI  - Pustulotic arthroosteitis: spectrum of bone lesions with palmoplantar pustulosis.
AB  - PURPOSE: To discuss the association of palmoplantar pustulosis (PPP) with
      sternocostoclavicular hyperostosis (SCCH) and other infection- or tumor
      simulating bone lesions. MATERIALS AND METHODS: From 1989 to 1992, 25 patients
      (11 men and 14 women, aged 19-69 years [mean, 42 years]) with pustulotic
      arthroosteitis (PAO) and SCCH were seen. Findings were accumulated to determine
      the concomitant findings of other bone lesions. RESULTS: Thirteen patients with
      skeletal lesions had proved PPP. Eleven of these patients also had SCCH, four had
      sacroiliitis, six had spondylitis, and six had tumorlike manifestations in the
      appendicular skeleton. In another 12 patients with SCCH, none had proved PPP but
      four had psoriasis. Fifteen of 25 patients with SCCH had skin disease. Seven of
      the 25 patients had only one site of bone involvement (six had SCCH and one had
      spondylitis); all other patients (including the six with tumor-simulating
      extraaxial lesions) had more than one skeletal site of bone involvement.
      CONCLUSION: Because radiologists play the key role in the diagnosis of PAO,
      awareness of the possibility of benign disease is necessary to obviate certain
      diagnostic or therapeutic procedures.

PMID- 8134573
TI  - US analysis of adnexal masses: the art of making the correct diagnosis.

PMID- 8134574
TI  - Stress radiography of the medial elbow ligaments.
AB  - PURPOSE: To study the usefulness of stress radiography for evaluation of injury
      to the medial collateral ligament (MCL). MATERIALS AND METHODS: Forty-two injured
      athletes and four healthy athletes without symptoms underwent examination
      performed with a stress device. The increase in joint space width between the
      medial epicondyle and coronoid process, measured on anteroposterior radiographs
      obtained after 0 and 15 daN force was applied to the lateral elbow joint, was
      used to assess the extent of ligament tear. The validity of this technique was
      tested with study of selectively severed cadaveric MCLs. RESULTS: All complete
      and large partial tears were correctly diagnosed with stress radiography when the
      increase in joint space width was larger by 0.5 mm in the affected elbow compared
      with the opposite normal elbow. In subjects with values less than 0.5 mm, the
      MCLs were normal or showed a small tear that could be managed conservatively.
      CONCLUSION: Stress radiography of the MCL enables accurate diagnosis of large and
      complete tears and distinction between such tears and small partial tears and
      normal ligaments.

PMID- 8134575
TI  - Osteoid osteoma: MR imaging versus CT.
AB  - PURPOSE: To compare the performance of computed tomography (CT) and magnetic
      resonance (MR) imaging in diagnosis of osteoid osteoma. MATERIALS AND METHODS:
      Nineteen patients with histologically proved osteoid osteoma underwent CT and MR
      imaging before excision of the lesion. CT and MR images were compared regarding
      lesion conspicuity and detection of marrow, soft-tissue, and/or synovial changes
      adjacent to the primary lesion. RESULTS: CT was more accurate than MR imaging in
      detection of the osteoid osteoma nidus in 63% of cases. MR imaging was better
      than CT in showing intramedullary and soft-tissue changes in all cases. This may
      produce a misleading aggressive appearance on MR images. There was a
      statistically significant correlation between presence or absence of marrow or
      soft-tissue changes and treatment with antiinflammatory medications (P < .05).
      CONCLUSION: CT remains the best imaging modality for diagnosis of osteoid
      osteoma. MR images should not be interpreted without reference to plain
      radiographs and CT scans if serious errors in diagnosis are to be avoided.

PMID- 8134576
TI  - MR lymphography: study of a high-efficiency lymphotrophic agent.
AB  - PURPOSE: To investigate the utility of a monocrystalline iron oxide nanoparticle
      (MION) as a contrast agent in magnetic resonance (MR) imaging of lymph nodes.
      MATERIALS AND METHODS: Pharmacokinetic data were obtained in rats after
      intravenous, subcutaneous, and intraarterial injection of indium-111-MION-46. MR
      imaging was performed to determine optimal dosages and pulse sequences in rats.
      Models of lymph node metastasis in rabbits and lymph node hyperplasia in rats
      were used to demonstrate the efficacy of MION in differentiation of malignant and
      benign adenopathies. RESULTS: Biokinetic data indicate that nodal accumulation
      occurs primarily after extravasation of agent into the interstitial space (slow
      component) and subsequent trapping by lymph node macrophages (fast component).
      Relatively low concentrations (15-25 mumol Fe per kilogram for peripheral nodes
      after intraarterial injection) decrease signal intensity of nodes at MR imaging.
      CONCLUSIONS: Lymph node accumulation of MION-46 is high. Modification of
      injection techniques that alter capillary permeability allows use of systemically
      administered agent at doses as low as 15-25 mumol Fe per kilogram.

PMID- 8134577
TI  - Intraarterial thrombolysis: triumph of confusion over consensus.

PMID- 8134578
TI  - Radiation-induced bone abnormalities after bone marrow transplantation for
      childhood leukemia.
AB  - PURPOSE: To identify bone abnormalities related to total-body irradiation (TBI)
      in long-term survivors of bone marrow transplantation (BMT) for childhood
      leukemia. MATERIALS AND METHODS: The authors obtained skeletal surveys of 10
      survivors of childhood leukemia, ages 5-27 years, who had undergone BMT 7-9 years
      previously. Pretransplantation "conditioning" regimens were composed of
      chemotherapy and TBI in doses of 12 or 14.4 Gy. RESULTS: Of the six survivors who
      received TBI before age 8 years, five had osteochondromas and three had
      metaphyseal growth abnormalities. One also had slipped femoral capital epiphysis.
      Findings in the four remaining patients, who received TBI at ages 12-19 years,
      were less severe and less clearly related to TBI (mild scoliosis in two cases,
      avascular necrosis of the femoral condyles in one, and a femoral enchondroma in
      one). CONCLUSIONS: Skeletal abnormalities, previously recognized as sequelae of
      local external-beam irradiation in children, may occur in long-term survivors of
      BMT who have received TBI. Younger patients appear to be at the greatest risk.

PMID- 8134579
TI  - Screening-detected and symptomatic ductal carcinoma in situ: mammographic
      features with pathologic correlation.
AB  - PURPOSE: To compare the mammographic and pathologic features of screening
      detected and symptomatic ductal carcinoma in situ (DCIS). MATERIALS AND METHODS:
      The mammographic and pathologic features of 54 screening-detected and 77
      symptomatic cases of DCIS were compared. Patients were aged 30-76 years (mean, 58
      years). RESULTS: Diffuse involvement was seen in 10 patients (13%) with symptoms
      but in none of the screening-detected group (P < .05). The disease was
      radiologically more extensive in the symptomatic group. Calcifications in the
      symptomatic group (n = 48) were less likely to have a ductal distribution than
      those in the screening-detected group (n = 48) (30 [63%] vs 40 [83%],
      respectively; P < .05). At histologic examination in some cases, the symptomatic
      group (n = 76) included eight (11%) patients with cribriform-micropapillary,
      large-cell tumors (P < .05) and less comedocarcinoma (20 [26%] vs 23 [45%],
      respectively; P < .05) compared with the screening-detected group (n = 51).
      CONCLUSION: The results show differences in the radiologic and pathologic
      features of screening-detected and symptomatic DCIS.

PMID- 8134580
TI  - Benefit of independent double reading in a population-based mammography screening
      program.
AB  - PURPOSE: To evaluate independent double reading in mammography screening and,
      specifically, the effect on breast cancer detection. MATERIALS AND METHODS:
      Mammographic studies of 11,343 women, aged 41-75 years, who participated in a
      population-based screening program were independently screened by two experienced
      radiologists. A retrospective analysis also was performed from notations made for
      patient recalls. RESULTS: Including follow-up of recalled women, 131 surgical
      biopsies were performed, which resulted in 76 histologically proved breast
      cancers. Fifty-six cancerous lesions were detected by both screeners. One
      screener detected 14 cancerous lesions alone, and the other detected six alone.
      Of the cancerous lesions detected by only one screener, 85% were stage 0 or 1,
      compared with 59% of those detected by both screeners. Double reading detected
      15% (95% confidence interval, +/- 7%) more cancer cases with an almost unchanged
      positive predictive value of 0.6. CONCLUSION: Independent double reading does
      significantly increase sensitivity of mammography screening.

PMID- 8134581
TI  - Imaging of pregnancy-associated breast cancer.
AB  - PURPOSE: To assess the use of mammography in diagnosis of pregnancy-associated
      breast cancer (PABC). MATERIALS AND METHODS: A retrospective review of medical
      records between 1973 and 1993 was performed in 85 women with breast cancer
      diagnosed during pregnancy or within 1 year after pregnancy. In 21 of these
      women, mammography was performed before biopsy; the mammographic findings in this
      study group, which had 23 cases of invasive carcinoma, were reviewed for signs of
      malignancy. Breast sonography was performed in six cases in five women;
      sonographic findings were also reviewed. RESULTS: Mammographic findings were
      present in 18 of 23 cases (78%), including mass (n = 13) (nine cases with
      calcification), suspicious calcifications (n = 4), and diffusely increased
      parenchymal density (n = 1). Breast sonography revealed focal solid mass in six
      of six cases. Axillary lymph node metastases occurred in 15 of 23 cases (65%).
      Although symptoms occurred before or during pregnancy in 12 cases (52%), PABC was
      diagnosed after pregnancy in 19 cases (83%). CONCLUSION: PABC is often advanced
      at diagnosis and associated with poor prognosis. Breast imaging studies usually
      demonstrate focal findings due to clinically evident PABC.

PMID- 8134582
TI  - Cholesterol granuloma of the breast: a mimic of carcinoma.
AB  - Cholesterol granuloma of the breast is a rare condition that may be related to
      the common disorder mammary duct ectasia. Its importance is in its tendency to
      mimic carcinoma clinically and radiologically. The authors report a case in a 65
      year-old asymptomatic woman.

PMID- 8134583
TI  - Chest wall and mediastinal invasion by lung cancer: evaluation with multisection
      expiratory dynamic CT.
AB  - PURPOSE: To assess the utility of multisection expiratory dynamic (ED) computed
      tomography (CT) in evaluation of tumor invasion in the chest wall or mediastinum.
      MATERIALS AND METHODS: Fifteen patients with lung cancer underwent multisection
      ED CT. At each section level, 10 images were obtained at an interval of 1 second
      during a single expiratory maneuver. These images were evaluated in cine mode to
      assess tumoral movement along the chest wall or mediastinum. RESULTS: ED CT
      showed that the tumors in five patients were fixed to the chest wall (n = 2) or
      mediastinum (n = 3); free movement of tumor along the peripheral (n = 7) or
      mediastinal (n = 3) pleura was proved in the 10 other patients. At pathologic
      examination, the ED CT findings were proved correct in all patients. In six
      patients, ED CT provided additional information about tumor invasion that could
      not be obtained with conventional criteria. CONCLUSION: Multisection ED CT may
      improve the accuracy of CT in prediction of chest wall or mediastinal invasion of
      lung cancer.

PMID- 8134584
TI  - Use of quantitative CT to predict postoperative lung function in patients with
      lung cancer.
AB  - PURPOSE: To evaluate the effectiveness of quantitative computed tomography (CT)
      for predicting postoperative lung function in patients with lung cancer.
      MATERIALS AND METHODS: Preoperative spirometry and conventional CT of the chest
      were performed in 38 patients. A postprocessing CT program was applied to
      quantitate the volume of whole-lung parenchyma with attenuations of -500 to -910
      HU; this was defined as total functional lung volume (TFLV). The regional
      functional lung volume (RFLV) of the lobes or lung to be resected was quantitated
      separately. CT-predicted postoperative forced expiratory volume in 1 second
      (FEV1) and forced vital capacity (FVC) were derived by multiplying the
      preoperative spirometry values by (1 - RFLV/TFLV). RESULTS: CT-predicted values
      correlated well with postoperatively measured results (FEV1: r = .93, P < .001;
      FVC: r = .86, P < .001) in patients who underwent pneumonectomy or lobectomy,
      regardless of the patient's preoperative ventilation status. CONCLUSION: This
      method is effective in the prediction of postoperative FEV1 and FVC in patients
      undergoing pulmonary resection.

PMID- 8134585
TI  - Enlarged mediastinal lymph nodes in bronchogenic carcinoma: assessment with
      dynamic contrast-enhanced MR imaging. Work in progress.
AB  - PURPOSE: To determine whether dynamic contrast material-enhanced magnetic
      resonance (MR) imaging can help differentiate between malignant and benign
      mediastinal lymph nodes (MLNs) in bronchogenic carcinoma. MATERIALS AND METHODS:
      Nine patients with biopsy-proved lung carcinoma underwent dynamic contrast
      enhanced MR imaging before undergoing thoracic surgery. MR studies included spin
      echo, electrocardiographically gated axial and coronal sequences and transaxial
      gradient-echo breath-hold sequences, which were performed after administration of
      a bolus of gadoterate meglumine. The enhancement curves were established on the
      basis of mean signal intensities from regions of interest at the level of tumor
      and the enlarged MLN. MR images were compared with pathologic specimens obtained
      at surgical resection. RESULTS: Metastatic MLNs exhibited their peak enhancement
      at 60-80 seconds, with a slow decrease until 6 minutes. Granulomatous and
      anthracotic lymph nodes displayed a slight enhancement, with no peak within 6
      minutes (P < .01). CONCLUSION: Dynamic contrast-enhanced MR images may provide
      informative data about the nature of enlarged MLNs in the preoperative assessment
      of lung carcinoma. Further studies are needed to investigate its usefulness in
      clinical practice.

PMID- 8134586
TI  - Dr Henry Garland: the man, the myth, the legend, and the legacy. Garland Lecture
      from the 1991 California Radiological Society meeting.
AB  - In a century of American radiology, a relatively small number of radiologists
      have emerged as unquestioned leaders of the specialty. One of those was L. Henry
      Garland, late of San Francisco, whose multifaceted accomplishments and vigorous
      personality made him a significant contributor to advances in radiology during 3
      decades. The Garland family has endowed an annual lecture at the meeting of the
      California Radiological Society. This essay is taken from the 1991 lecture, which
      was an assessment of Garland's significance.

PMID- 8134587
TI  - Transvenous and subcutaneous implantable cardioverter defibrillators:
      radiographic assessment.
AB  - PURPOSE: To assess chest radiograph configurations in 102 patients following
      total or partial transvenous and subcutaneous insertion of a non-thoracotomy lead
      implantable cardioverter defibrillator (NTL-ICD) device. MATERIALS AND METHODS:
      The four overlapping system types reviewed were the Endotak (49 patients), PCD
      (32 patients), Res-Q (10 patients), and hybrid combinations of NTL-ICD and
      surgically inserted pericardial and epicardial automatic implantable cardioverter
      defibrillator (AICD) devices (15 patients). RESULTS: Abnormalities were detected
      on radiographs both at the time of implantation and at early follow-up. NTL-ICD
      electrodes partially replaced or augmented AICD systems in 11 patients (10.7%)
      because of sensing lead or defibrillation failure or infection. Defibrillation
      failure necessitated augmentation of NTL-ICD systems with AICD pericardial
      patches in four patients (3.9%). Catheter displacement, lead fracture, or
      pneumothorax was detected in eight patients (7.8%). CONCLUSION: Complex
      radiographic appearances may be seen and important abnormalities may be detected
      after insertion of these devices.

PMID- 8134588
TI  - Necrosis in pontine gliomas: radiation induced or natural history?
AB  - PURPOSE: To determine whether the central necrotic lesions that develop in a
      large number of patients with pontine gliomas are secondary to radiation therapy,
      specifically high-dose (7,200-7,800 cGy) hyperfractionation radiation therapy, or
      are part of the biologic progression of this tumor. MATERIALS AND METHODS: The
      authors analyzed neuroimaging studies of 31 consecutive patients with pontine
      centered gliomas and assessed the time of onset of necrosis, the type and dose of
      radiation therapy administered, and the length of survival. RESULTS: Necrosis was
      present at diagnosis in eight of the 31 patients (26%). Time to appearance and
      total prevalence of central necrosis did not differ in the standard versus
      hyperfractionated therapy groups. The time between diagnosis and the appearance
      of necrosis correlated with length of survival (P = .005, Kendall correlation).
      CONCLUSION: In a substantial number of patients, central necrosis in pontine
      gliomas is not caused by radiation therapy but is an indication of an advanced
      tumor stage. Children with central necrosis at diagnosis have a significantly
      shorter median survival than do those without, regardless of the type of therapy
      administered.

PMID- 8134589
TI  - Pancreas transplants: efficacy of US-guided cystoscopic biopsy.
AB  - Between December 1991 and June 1993, the authors performed cystoscopic
      transduodenal biopsy of pancreas transplants in 35 consecutive patients (18 men
      and 17 women, aged 22-48 years [mean, 34 years]). The first 12 biopsies were
      performed under direct visualization and the last 23 were performed with
      ultrasonographic (US) guidance. Specimens were adequate for pathologic diagnosis
      in nine of 12 (75%) and in 22 of 23 (96%) biopsies, respectively. US-guided
      biopsy of pancreas transplants is safe and effective and gives increased
      diagnostic yield.

PMID- 8134590
TI  - Nonendoscopic gastric mucosal biopsy to augment double-contrast upper
      gastrointestinal barium examination.
AB  - The authors present a gastric mucosal biopsy technique with use of a nasogastric
      catheter and biopsy forceps after double-contrast upper gastrointestinal
      fluoroscopy in patients with clinical symptoms of dyspepsia. In 51 patients (18
      men and 33 women, aged 27-73 years [mean, 46 years]), 136 aggregates (specimens
      composed of the two pieces of mucosal tissue obtained in each region) ranged from
      0.1 to 0.6 cm in diameter. All but three specimens were of adequate mucosal
      depth. No complications secondary to bleeding resulted.

PMID- 8134591
TI  - Neuroimaging of juvenile pilocytic astrocytomas.

PMID- 8134593
TI  - Neural networks.

PMID- 8134592
TI  - Diagnosis of pulmonary embolism: no fooling around.

PMID- 8134594
TI  - Occult intracranial aneurysms in polycystic kidney disease: screening with MR
      angiography.
AB  - PURPOSE: To estimate the prevalence, location, and type of cerebral aneurysms in
      patients with adult polycystic kidney disease (PCKD) and identify associated risk
      factors. MATERIALS AND METHODS: Ninety-three patients with PCKD were screened for
      aneurysms with spin-echo parenchymal magnetic resonance (MR) imaging and three
      dimensional time-of-flight MR angiography. Prevalence was estimated with the
      calculated proportions of patients who had aneurysms, adjusted for reported
      sensitivity and specificity of MR angiography. RESULTS: Thirteen aneurysms, found
      in 10 patients, were 7 mm or smaller in largest dimension; 11 of these aneurysms
      were saccular. Intra- and interobserver variabilities were 96%-98%. Conventional
      arteriograms, obtained in six patients, helped confirm the MR angiographic
      findings. The best estimates of prevalence of aneurysms were 11.7% in the study
      group (n = 93) and 25.8% in patients with a family history of aneurysms (n = 6).
      CONCLUSION: The prevalence of aneurysms in the study group was greater than in
      the general population. MR angiography is useful in screening for cerebral
      aneurysms.

PMID- 8134595
TI  - Specialization: practical or impractical?

PMID- 8134596
TI  - Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic
      findings.
AB  - PURPOSE: To assess the utility of magnetic resonance (MR) cerebral blood volume
      (CBV) maps in the evaluation of gliomas. MATERIALS AND METHODS: CBV maps from 19
      patients with histologically proved gliomas were calculated from dynamic MR image
      sets acquired with echo-planar spin-echo imaging after intravenous injection of
      gadolinium-based contrast material. RESULTS: The maximum CBV varied from 0.82 to
      5.40 in the high-grade group (n = 13) and from 1.01 to 1.21 in the low-grade
      group (n = 6). The difference was statistically significant. Maximum CBV was
      associated with mitotic activity and vascularity, but not with cellular atypia,
      endothelial proliferation, necrosis, or cellularity. CONCLUSION: MR CBV maps
      provided diagnostic information not available with conventional MR imaging in six
      cases and offers a functional parameter for assessing glioma grade and regions of
      focal activity.

PMID- 8134597
TI  - Kallman syndrome versus idiopathic hypogonadotropic hypogonadism at MR imaging.
AB  - PURPOSE: To identify morphologic differences between Kallman syndrome (KS) and
      idiopathic hypogonadotropic hypogonadism (IHH) and establish a role for magnetic
      resonance (MR) imaging in these disorders. MATERIALS AND METHODS: Twenty-eight
      patients were compared with 10 eugonal male volunteers. Eighteen patients had KS
      (hypogonadotropic hypogonadism with anosmia) and 10 had IHH. All participants
      underwent hormone analysis, a sniff-bottle smell test, and gadolinium-enhanced MR
      imaging. Changes in the hypothalamic-hypophyseal region and the rhinencephalon
      were evaluated. RESULTS: MR imaging revealed intracranial morphologic changes in
      all patients on plain T1-weighted sections. Seventeen patients with KS
      demonstrated aplasia of an olfactory bulb; one olfactory sulcus was absent in
      six, rudimentary in four, and normal in eight. Olfactory bulbs were present in
      all 10 IHH patients and three showed one slightly hypoplastic bulb. Ten patients
      with KS and three with IHH showed an enlarged paranasal sinus system. Further MR
      findings were similar. CONCLUSION: MR imaging demonstrates abnormalities of the
      rhinencephalon present in KS patients and occasionally absent in IHH patients.

PMID- 8134598
TI  - Optic nerve coloboma (morning glory syndrome): CT findings.
AB  - This study demonstrates computed tomographic (CT) findings of morning glory
      syndrome. CT examination of the orbits was performed in three patients. Images of
      2-mm-thick sections were acquired at 2-mm intervals without use of contrast
      material. Excellent demonstration of coloboma was achieved in each case. Because
      both magnetic resonance imaging and ultrasonography have limitations in imaging
      of coloboma, CT is the imaging method of choice in diagnosis of this disorder.

PMID- 8134599
TI  - Prospective evaluation of adnexal masses with endovaginal gray-scale and duplex
      and color Doppler US: correlation with pathologic findings.
AB  - PURPOSE: To assess the reliability of gray-scale and color and duplex Doppler
      ultrasound (US) in making a specific diagnosis of malignant ovarian tumor.
      MATERIALS AND METHODS: Forty-two women with 50 adnexal masses underwent
      endovaginal and color and duplex Doppler US. Morphologic characteristics were
      evaluated with endovaginal US, and flow velocity patterns were evaluated with
      color and duplex Doppler US. The results were compared with pathologic findings.
      RESULTS: At pathologic examination, 40 masses (80%) were benign, one (2%) was
      borderline malignant, and nine (18%) were malignant. Endovaginal US enabled
      correct diagnosis of 38 of the 40 benign masses (95%) and all nine malignant
      masses (100%). Color and duplex Doppler US enabled correct diagnosis of 33 benign
      masses (82%) and seven malignant masses (78%). CONCLUSION: Because there is an
      overlap in the resistive index (RI) values of benign and malignant masses, RI
      values alone cannot be relied on. Combining the detailed analysis of internal
      architectural appearance with the flow velocity patterns obtained at pulsed
      Doppler US increases the specificity in the diagnosis of adnexal masses.

PMID- 8134600
TI  - Sequential contrast-enhanced MR imaging of the penis.
AB  - PURPOSE: To determine the enhancement patterns of the penis at magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Sequential contrast material-enhanced MR
      images of the penis in a flaccid state were obtained in 16 volunteers (12 with
      normal penile function and four with erectile dysfunction). RESULTS: Subjects
      with normal erectile function showed gradual and centrifugal enhancement of the
      corpora cavernosa, while those with erectile dysfunction showed poor enhancement
      with abnormal progression. CONCLUSION: Sequential contrast-enhanced MR imaging
      provides additional morphologic information for the evaluation of erectile
      dysfunction.

PMID- 8134601
TI  - Stair-step artifacts in three-dimensional helical CT: an experimental study.
AB  - PURPOSE: Stair-step artifacts in helical computed tomography (CT) are associated
      with inclined surfaces in longitudinal sections. The authors investigated the
      origin and the characteristics of the artifacts. MATERIALS AND METHODS: A cone
      phantom and a skull were dry-scanned with a helical CT scanner, and images were
      reconstructed by using the half-scan interpolation algorithm with combinations of
      detector collimation (1 and 5 mm), table feed (1, 2, 5, and 10 mm), and
      reconstruction interval (1, 2, 5, and 10 mm). RESULTS: Stair-step artifacts were
      perceived in most instances. Stair-step artifacts arose from two sources: large
      reconstruction intervals and asymmetric helix interpolation, forming isoclosed
      curves and spirallike patterns in three-dimensional axial views, respectively.
      CONCLUSION: To eliminate the stair-step artifacts, both the collimation and the
      table feed should be less than the longitudinal dimension of the important
      feature on inclined surfaces, and the reconstruction interval should be less than
      the table feed. Adaptive interpolation may correct the artifacts.

PMID- 8134602
TI  - Inversion in the steady state: contrast optimization and reduced imaging time
      with fast three-dimensional inversion-recovery-prepared GRE pulse sequences.
AB  - PURPOSE: To evaluate the differences in contrast between 1-second delay and zero
      delay (for magnetization recovery) before the preparation radio-frequency pulse
      in three-dimensional, inversion-recovery (IR) fast gradient-echo (GRE)
      acquisitions. MATERIALS AND METHODS: Mathematical simulations and measurements of
      brain image contrast were performed with healthy volunteers and 10 patients.
      RESULTS: The zero-delay sequence generated T1-weighted contrast similar to that
      obtained with 1-second delay but was accompanied by a substantial reduction in
      imaging time. However, the zero delay prohibits full recovery of the longitudinal
      magnetization. Hence, the signal null characteristic of IR experiments is not
      easily observed, since it occurs (as a function of tissue T1) at very short
      inversion times (< 150 msec). CONCLUSION: T1-weighted contrast comparable with
      that of magnetization-prepared rapid GRE sequences with a 1-second delay and
      preparation time (TP) of 600-700 msec can be achieved in less time by using a
      zero delay and a shorter TP (400-500 msec).

PMID- 8134603
TI  - Measurement of acoustic noise during MR imaging: evaluation of six "worst-case"
      pulse sequences.
AB  - PURPOSE: To assess acoustic noise levels for ambient noise and magnetic resonance
      (MR) imaging at 1.5 T during use of six "worst-case" pulse sequences. MATERIALS
      AND METHODS: Acoustic noise measurements were obtained at the entrance, center,
      and exit of the magnet bore of the MR system by means of a specially modified
      device that is unaffected by electromagnetic radiation. RESULTS: The highest
      ambient noise level was 73 dB at both the entrance and exit of the magnet bore (A
      weighted scale). The highest noise levels during MR imaging occurred during use
      of a gradient-echo (GRE) pulse sequence and was 102 dB at the entrance and exit
      of the magnet bore and 103 dB at the center (A-weighted scale). CONCLUSIONS: MR
      imaging performed with the worst-case pulse sequences did not produce noise
      levels that exceeded federal guidelines. Noise levels were, however, high enough
      to impair oral communication and annoy patients. Thus, techniques to attenuate
      acoustic noise and allow improved operator-patient communication should be used
      during MR imaging, especially during use of GRE pulse sequences.

PMID- 8134604
TI  - Globus pharyngeus: radiographic evaluation and 24-hour pH monitoring of the
      pharynx and esophagus in 22 patients.
AB  - PURPOSE: The authors correlated the radiographic evaluation and 24-hour pH
      monitoring of the pharynx and the esophagus in patients with globus pharyngeus.
      MATERIALS AND METHODS: Radiographic examination of the pharynx of 22 patients (13
      women and nine men, aged 23-73 years [mean, 47 years]) included videofluoroscopy
      and static radiography. Twenty-four-hour double-probe pH monitoring of the
      pharynx (abnormal, pH < 4) and esophagus (abnormal, 6% or more total acid
      exposure) was performed in all patients. RESULTS: Radiographic results were
      normal in 17 patients; results were abnormal in five, with four having pharyngeal
      dysfunction and one showing a persistent cricopharyngeal impression. Zenker
      diverticulum was not seen. Results at pH monitoring of the pharynx and esophagus
      were normal in 20 and 18 of the 22 patients, respectively. In four of five
      patients with abnormal radiographic studies of the pharynx, results of pharyngeal
      pH monitoring were normal. CONCLUSION: Most patients with globus pharyngeus had
      normal results at pH monitoring and radiographic examination of the pharynx.

PMID- 8134605
TI  - Which hurts the most? A comparison of pain rating during double-contrast barium
      enema examination and colonoscopy.
AB  - PURPOSE: To study the degree of pain caused by double-contrast barium enema
      examination and colonoscopy and to compare pain ratings by patients and medical
      personnel. MATERIALS AND METHODS: In a random sample, 190 patients (aged 45-79
      years) (mean, 63.1 years) recorded their experiences of pain during each
      procedure and the medical staff recorded their impressions of the patients' pain,
      on a 10-point progressive scale. The data were analyzed with the Wilcoxon rank
      test, Spearman rank correlation, and generalized kappa value. RESULTS: Patients'
      pain ratings were significantly higher during colonoscopy than during double
      contrast barium enema examination (P < .0001). Pain was rated significantly
      higher by patients than by personnel for both procedures (P < .0001). CONCLUSION:
      In the choice of procedure, patients' high level of pain during colonoscopy
      should be remembered. The medical staff frequently underestimated patients' pain
      during both procedures, and this study documents a need for more extensive pain
      relief measures during potentially painful examinations of the large bowel.

PMID- 8134606
TI  - Writing functional abstracts.

PMID- 8134607
TI  - The effects of attendance and effort on outcomes among older adults in a long
      term exercise program.
AB  - To determine if attendance and effort could differentiate changes in cognitive
      and physical functioning, 66 older adults received a prescription heart rate to
      be achieved during supervised regular exercise sessions over a 9-month period.
      These 30-min sessions of aerobic training on a cycle ergometer were conducted
      three times per week. Cognitive variables and physical functioning were measured
      at baseline and following 4.5 months and 9 months of training. Attendance and
      effort scores (ATTEFF) were used to divide subjects into low ATTEFF (N = 29) and
      high ATTEFF (N = 37) groups. Following 9 months of training these groups were
      significantly different on life satisfaction and selected measures of health
      perception, but not on measures of either mental status or submaximum or resting
      heart rate. Maximum physical functioning improved within both groups, although
      the high ATTEFF group had improved more than the low ATTEFF group at posttest.
      Attendance and effort appear to differentiate older adults on selected measures
      of health perception and maximum physical functioning following a 9-month
      exercise program.

PMID- 8134608
TI  - The effects of child temperament, maternal characteristics, and family
      circumstances on the maladjustment of school-age children.
AB  - Eighty-nine mothers with children between the ages of 8 and 11 years reported
      perceptions of their child's adjustment and temperament, and described concurrent
      family circumstances such as socioeconomic status, level of parental distress,
      major life events experienced, maternal hassles, and their own psychiatric
      symptoms. A conceptual model hypothesizing the direct and indirect effects of
      family circumstances, maternal characteristics, and child temperament on the
      maladjustment of school-age children was tested using causal modeling with
      residual analysis. Fifty-six percent of child externalizing behavior was directly
      explained by the negative reactivity and nonpersistence of the child's
      temperament, and maternal hassles. A total of 33% of the variance of
      internalizing behavior was explained by the direct effects of negative reactivity
      of the child's temperament and maternal hassles. For both externalizing and
      internalizing behavior, a total of 54% of the variance in maternal hassles was
      explained by three variables: maternal psychiatric symptoms contributed 34%,
      major life events added 15%, and the intensity of the mother's temperament added
      an additional 5%. These three variables have a direct effect on maternal hassles
      and together had an indirect effect of .24 on child externalizing behavior
      through maternal hassles. Likewise, they have a direct effect on maternal hassles
      and together had an indirect effect of .31 on child internalizing behavior
      through maternal hassles.

PMID- 8134609
TI  - Predictors of health-promoting lifestyles in persons with disabilities.
AB  - Persons with disabilities have been largely overlooked in investigations of
      health and health behaviors. The primary purpose of this descriptive
      correlational study was to examine the usefulness of Pender's (1987) Health
      Promotion Model in explaining the occurrence of health-promoting behaviors among
      adults with disabilities. Hierarchical multiple regression analyses were used to
      analyze questionnaire responses from a sample of 117 adults with disabilities.
      Adults with disabilities were more likely to engage in a health-promoting
      lifestyle if they had higher specific self-efficacy for health behaviors, higher
      general self-efficacy, a wellness-oriented definition of health, required less
      mechanical assistance, and were female. Findings from this study suggest that
      interventions aimed at enhancing health promotion behaviors among persons with
      disabilities would be strengthened by addressing perceived ability to master
      situations, particularly the ability to successfully carry out health-promoting
      behaviors.

PMID- 8134610
TI  - Maternal-fetal attachment: influence of mother-daughter and husband-wife
      relationships.
AB  - Intergenerational attachment relationships between the pregnant woman and her
      mother, her husband, and her fetus were examined. Self-completed instruments were
      used to measure the attachment variables for a convenience sample of 115 middle
      class mothers who attended urban prenatal classes. Results supported the
      hypothesis that mother-daughter and husband-wife attachment were correlated
      positively. Contrary to study predictions, maternal-fetal attachment scores were
      not related to mother-daughter and husband-wife attachment scores. Maternal-fetal
      attachment was related to length of gestation. Results provide only partial
      support for the intergenerational model of attachment relationships.

PMID- 8134611
TI  - Psychometric properties of the Driving Practices Questionnaire: assessment of
      risky driving.
AB  - A national public health goal is to reduce injuries and deaths from motor vehicle
      crashes (MVC). The development and psychometric evaluation of the 10-item Driving
      Practices Questionnaire (DPQ) to measure risky driving is described. Based on
      responses from 297 drivers divided into safe, unsafe, and injured groups, the DPQ
      was evaluated using item and factor analysis, and reliability and validity
      measures. Principal axis factor analysis isolated one factor with 42.3% of the
      variance explained. The alpha coefficient for the scale was .87 and test-retest
      correlation was .94. High DPQ scorers were three times more likely to have prior
      traffic violations. The identification of driver subtypes will assist the testing
      of injury prevention interventions.

PMID- 8134612
TI  - Retaining Army nurses: a longitudinal model.
AB  - A longitudinal sample of active duty Army nurses working in a broad range of
      nursing specialties and settings was analyzed for retention behavior. A turnover
      model of actual retention behavior, estimated using logistic regression, included
      external market, personal/demographic, and work-related variables as explanatory
      factors. Satisfaction with work and military life, satisfaction with
      location/assignment stability, race--ethnic group, and family status had
      significant effects on the retention of Army junior nurse-officers.

PMID- 8134613
TI  - Use of health records in research: reliability and validity issues.
AB  - Data extracted from health records are commonly used in studies to address a
      variety of questions raised by health researchers. However, concern about the
      reliability and validity of such data generally is limited to an assessment of
      interrater reliability. Less attention has been paid to the reliability of the
      health record itself, and to the validity of both the health record and the data
      extracted from it. This article reviews the distinctions and overlaps among these
      types of reliability and validity and the factors that influence the validity and
      reliability of research data obtained from health records. Recommendations to
      investigators who use health record data in their research projects are offered.

PMID- 8134614
TI  - Secretion of neurotensin from a human pancreatic islet cell carcinoma cell line
      (QGP-1N).
AB  - Effects of various secretagogues on secretion of neurotensin from a pancreatic
      islet cell carcinoma cell line (QGP-1N) were examined. Carbachol stimulated
      secretion of neurotensin concentration-dependently in the range of 10(-6) - 10(
      4) M. The neurotensin secretion stimulated with 10(-5) M carbachol was completely
      inhibited by atropine at 10(-5) M. Phorbol ester and calcium ionophore (A23187)
      stimulated secretion of neurotensin. The removal of extracellular Ca2+ suppressed
      the secretion through the stimulation with 10(-5) M carbachol. Fluoride, an
      activator of guanine nucleotide-binding (G) protein, stimulated secretion of
      neurotensin. Neurotensin released into culture medium through stimulation with
      carbachol coeluted with neurotensin 1-13 on a gel-chromatography. Our results
      suggest that secretion of neurotensin from QGP-1N cells is mainly regulated by
      acetylcholine through muscarinic receptors coupled to G protein and that an
      increase in intracellular Ca2+ and protein kinase C play an important role in
      stimulus-secretion coupling.

PMID- 8134615
TI  - Insulin-like growth factors enhance phagocytosis by human neutrophils in vitro.
AB  - Polymorphonuclear neutrophils (PMNs) were isolated from human blood, and PMN
      phagocytosis was assessed by measuring the chemiluminescence (CL) response in the
      presence of ZAP (opsonized zymosin particles containing luminol). The
      administration of 6.5 nM of insulin-like growth factor I (IGF-I), des(1-3)-IGF-I,
      IGF-II or insulin to PMNs for 20 min resulted in significant increases of the CL
      response for all test preparations. Des(1-3)-IGF-I, a truncated IGF-I with low
      affinity binding to IGF binding proteins (IGFBPs), was the most potent CL
      stimulator. The CL production evoked by 6.5 nM of des(1-3)-IGF-I was inhibited
      significantly by both 0.25 and 1.0 nM of EGTA (Ca2+ chelator), or 10 microM
      nifedipine (Ca2+ channel inhibitor), pertussis toxin (0.05 and 1.0 micrograms/ml)
      or cholera toxin (5 micrograms/ml). These results suggest that IGF-I and its
      homologues are potent stimulators of phagocytosis and that this action is
      modulated by IGFBP, and may require extracellular Ca2+ and/or IGF-I receptor G
      protein coupling.

PMID- 8134616
TI  - Characterization of an antiserum against an achetakinin I-analog and its use for
      the localization of Culekinin Depolarizing Peptide II in the mosquito, Culex
      salinarius.
AB  - ELISA experiments revealed that an antiserum raised against an achetakinin-analog
      could specifically detect the recently isolated Culekinin Depolarizing Peptide
      (CDP)-II from the mosquito, Culex salinarius. The characterization indicated that
      two different epitopes in the C-terminal region of achetakinin I and CDP-II are
      recognized. One epitope is the -F-Y-region, the other is the -P-W-region. Among
      the peptides isolated from C. salinarius, the antiserum reacts only with CDP-II.
      Pre-absorption tests of the antiserum with CDP-II in immunohistological stainings
      abolished the reaction, while tests with pre-immune sera did not cause any
      immunopositive reactions. In the mosquito head ganglia, immunoreactive neurons
      were detected in the pars lateralis, the optic lobe and the suboesophageal
      ganglion. Although some immunopositive axons extended into the nervi corporis
      cardiacii II, no immunoreactivity was observed in the retrocerebral complex. In
      the thoracic ganglia, immunoreactive neurons were found in the pro-, meso- and
      metathoracic neuromeres. No immunoreactivity was found elsewhere. With this study
      we demonstrate that CDP-II, isolated from a whole body extract, is truly a
      neuropeptide, and the data suggest that its function is neuromodulating or
      neurotransmitting rather than neurohormonal.

PMID- 8134617
TI  - Antisense inhibition of AT1 receptor mRNA and angiotensinogen mRNA in the brain
      of spontaneously hypertensive rats reduces hypertension of neurogenic origin.
AB  - To determine the role of angiotensinogen and angiotensin II type-1 (AT1) receptor
      genes in hypertension, spontaneously hypertensive rats (SHR) were injected with
      synthetic antisense oligodeoxynucleotides (ODNs), intracerebroventricularly
      (i.c.v). Antisense ODNs were constructed to bases -5 to +13 of angiotensinogen
      mRNA (18-mer) and to bases +63 to +77 (15-mer) of angiotensin II type-1 receptor
      mRNA. Hypertension was significantly reduced by the application of 50 micrograms
      of both antisense ODNs to normotensive levels. The phosphorothioated antisense
      ODN to the AT1 receptor produced long-lasting (7 days) decreases in blood
      pressure. After AT1 antisense treatment, AT1 receptors were reduced in the
      paraventricular nucleus (PVN) and in the anterior third ventricle area (AV3V).
      Following angiotensinogen antisense treatment, angiotensin II levels were
      significantly reduced in the brainstem (P < 0.05), indicating arrest of
      angiotensin II synthesis. The results demonstrate that inhibiting the brain renin
      angiotensin system by antisense inhibition of the angiotensinogen and the AT1
      receptor genes, lowers high blood pressure in the SHR. The antisense
      administration to specific genes of the tissue renin-angiotensin system offers
      the possibility of a new approach to developing antihypertension treatments.

PMID- 8134618
TI  - Neuropeptide Y: a central regulator of energy homeostasis.
AB  - Neuropeptide Y (NPY) is a 36 amino acid peptide belonging to the pancreatic
      polypeptide family of neuroendocrine hormones. It is the most abundant peptide
      yet discovered in the mammalian brain and is widely expressed by neurons in the
      central and peripheral nervous systems as well as adrenal medullary cells.
      Recently, a large number of studies have focussed on the potential roles played
      by NPY within the hypothalamus and pituitary with respect to the control of food
      intake and energy homeostasis. It is now clear that NPY is a potent stimulator of
      food intake in models of hyperphagia, that hypothalamic NPY also regulates
      sympathetic neural activity and it appears that NPY may also influence the
      glucocorticoid, growth hormone and thyroid hormone axes. Taken together, current
      data suggest that hypothalamic and pituitary NPY-expressing cells represent an
      important and critical site of integration of peripheral hormonal signals with
      regulation of energy homeostasis.

PMID- 8134619
TI  - The significance of recent highlights in heartwater research.
AB  - Many of the objectives identified earlier, with regard to research on cowdriosis,
      have been achieved during the past decade. Some contributions such as the
      development of Cowdria specific DNA probes and the attenuation of the organisms
      are still in the experimental stage but others, such as in vitro cultivation, are
      already well established practices in many laboratories. Serological techniques
      are now more widely used since other methods and other sources of antigen became
      available. However, persistent cross reactions with Ehrlichia still complicate
      the interpretation of epidemiological data. Biochemical studies to identify,
      isolate and characterize antigenic proteins present in Cowdria organisms revealed
      definite immunodominant proteins that could prove to be suitable antigens for
      serological tests. Despite these significant research advances, practical methods
      to diagnose and control the disease have remained virtually unchanged. Control is
      still based on either intensive tick control or in some cases on the
      establishment and maintenance of endemic stability. The infection and treatment
      method using infected blood or prophylactic treatment with tetracyclines, remains
      the backbone of disease control in South Africa. Heartwater will remain a threat
      to the American mainland for as long as Amblyomma variegatum is present in the
      Caribbean and eradication of the tick from that region seems indicated.

PMID- 8134620
TI  - Heartwater in Guadeloupe and in the Caribbean.
AB  - A sero-epidemiological survey for heartwater was organized in 1992 in the Lesser
      Antilles, from Grenada to Saint Martin. Blood from about one percent of the
      ruminant livestock of the islands was randomly sampled and the sera were tested
      with an indirect ELISA. The percentage of positive sera was found to be 30% in
      Guadeloupe, 25% in Antigua, 2.2% in St.Martin, 1.3% in St. Kitts & Nevis, 3.8% in
      Montserrat, 1.7% in Dominica, 1.5% in St.Lucia, 1.5% in St.Vincent, 3.5% in
      Barbados, 2.9% in Grenada and 7% in Martinique. Ruminants from Guadeloupe and
      Antigua are known to be infected with heartwater. The low percentage of positive
      sera and the absence of clinical cases in the other islands strongly suggest that
      positive sera in these islands are probably due to non-specific cross reactions
      between Cowdria and other micro-organisms (possibly Ehrlichia) which remain to be
      isolated. In particular, the high percentages of positive sheep sera in
      Martinique (15%) and Montserrat (11%) should be further investigated.

PMID- 8134621
TI  - Detection of antibodies to Cowdria ruminantium in the serum of domestic ruminants
      by indirect ELISA.
AB  - A solid phase enzyme immunoassay for the detection of antibodies to Cowdria
      ruminantium in the serum of domestic ruminants was developed by using
      microorganisms cultivated on bovine umbilical endothelial cells as antigen. When
      the culture showed 90% lysis, the supernatant was centrifuged, sonicated and
      coated on polystyrene microtiter plates. Antibodies were detected as early as 9
      days after experimental immunization of goats. The sensitivity of the ELISA
      calculated with 73 ruminant sera ranged between 97.3% and 98.6%. The overall
      specificity of the test was 97% (N = 2925). However, the specificity was far
      lower for sheep (94.4%, N = 881) than for goats (98.6%, N = 651) and cattle
      (97.8%, N = 1393). Crossreactivity which could explain some of the false positive
      reactions, was found between Cowdria antigen and sera raised against Ehrlichia
      bovis (1 bovine positive out of 2 inoculated) or E. ovina (2 sheep out of 2
      inoculated became positive) but not with E. phagocytophila. The intra-assay and
      inter-assay variability were 7.5% and 7.8% respectively, indicating a good
      reproducibility of the ELISA.

PMID- 8134622
TI  - The sero-diagnosis of heartwater: a comparison of five tests.
AB  - Five serological tests, the indirect and competitive ELISA, the indirect
      fluorescent antibody (IFA) test with 2 different antigens and the Western blot
      technique were compared and applied to sera that were known to be either negative
      or positive against Cowdria ruminantium or that were collected from animals in
      heartwater-free regions. No false positive reactions were recorded with any of
      the tests against the known negative sera. Except for minor variations in the
      sensitivity of the 5 tests, there was good correlation between them. Their
      specificity, however, remains in dispute since in all 5 tests extensive cross
      reactions were recorded with antibodies in response to an as yet unidentified
      agent, probably Ehrlichia.

PMID- 8134623
TI  - The relationship between Cowdria and Ehrlichia: change in the behaviour of
      ehrlichial agents passaged through Amblyomma hebraeum.
AB  - Following an earlier report that an Ehrlichia-like agent isolated from an adult
      Hyalomma truncatum female became more pathogenic and elicited a disease in sheep
      indistinguishable from heartwater after having been passaged through Amblyomma
      hebraeum, a similar phenomenon is herewith recorded. An ehrlichial agent
      demonstrated in the blood smear of a serologically positive, naturally infected
      lamb, changed in behaviour and assumed the characteristics of Cowdria after
      passage through A. hebraeum. Cross-immunity between sheep that had recovered from
      infection with the transformed agent and several stocks of Cowdria ruminantium
      confirmed the close relationship between the putative ehrlichial agent and
      Cowdria. Seven other sheep/tick passage lines resulted in high antibody titres
      and resistance to challenge with C. ruminantium in the sheep in the case of 2 of
      them, suggesting a similar change in behaviour of the agents passaged through
      Amblyomma.

PMID- 8134624
TI  - The immunodominant 32-kilodalton protein of Cowdria ruminantium is conserved
      within the genus Ehrlichia.
AB  - Serological tests for cowdriosis are hampered by cross-reacting antibodies from
      animals suspected to be infected with Ehrlichia species. We have monitored
      infections with Ehrlichia bovis, E. ovina, E. canis and E. phagocytophila in
      experimental animals by competitive ELISA, Western blotting and
      immunofluorescence using Cowdria-infected endothelial cell culture antigens.
      Cross-reactions due to Ehrlichia antibodies could be attributed to the
      recognition of epitopes on the immunodominant Cr32 Cowdria protein. This was
      especially true for E. canis and E. ovina, much less for E. bovis, but not at all
      for E. phagocytophila. In addition, strong cross-reactivity between Cowdria and
      antibodies to E. Chaffeenis were demonstrated. These findings are in agreement
      with the phylogenetic relationships, recently reported by van Vliet et al. in
      1992, between Cowdria and other members of the tribe Ehrlichieae, which showed
      Cowdria to be closely related to E. canis and also to E. chaffeensis. Although
      the tests used in this study remain valuable tools under laboratory conditions,
      their specificity requires improvement. It is suggested to study recombinant
      Cowdria antigens for the development of second generation serological tests for
      cowdriosis.

PMID- 8134625
TI  - Bovine and human endothelial cell growth on collagen microspheres and their
      infection with the rickettsia Cowdria ruminantium: prospects for cells and
      vaccine production.
AB  - We successfully cultivated the rickettsia Cowdria ruminantium, in bovine
      endothelial cell lines (Bovine Umbilical Endothelial Cells/BUEC and Bovine
      microvasculature Cells/BMC) and also in primary endothelial cells of bovine
      origin (Bovine Aorta Endothelial cells/BAEC) and more surprisingly in cells of
      human origin--Human Umbilical Vein Endothelial Cells/HUVEC--and Human Endothelial
      Cells from the Microvasculature/HEMEC. This first evidence of the pathogenicity
      of this bovine rickettsia in the human cell system gene-rates new interest as
      regards its possible relevance for human health. It provides also further
      possibilities for the attenuation of Cowdria ruminantium isolates, and therefore
      brings new prospects for vaccine preparation. In vaccine production, mass cell
      culture is essential. Our results indicate that endothelial cells attach
      efficiently on collagen microspheres. As BAEC cells grow well on them in a batch
      mode, and if the process could be optimized for the different cell types (using
      appropriate adhesion and growth factors) our observations offer interesting
      prospects for the future development of a Cowdria ruminantium vaccine production
      in the fluidized-bed reactor VERAX System one, which provides easy control of
      growth conditions.

PMID- 8134626
TI  - Isolation and characterization of antigenic proteins of Cowdria ruminantium.
AB  - Two antigenically conserved Cowdria ruminantium proteins, an immunodominant 31
      kDa and a minor 27 kDa protein, were characterized. The 31 kDa and 27 kDa
      proteins are single polypeptide chains. The 31 kDa protein contains no
      glycoconjugates and the partial, internal amino acid sequence was determined. The
      acidic nature of this protein, deduced from the amino acid composition, was
      confirmed by IEF (pI 5.7). Monospecific antiserum was prepared against the 27 and
      31 kDa proteins and results indicate that they are immunogenic and share common
      epitopes.

PMID- 8134627
TI  - Cloning and partial characterization of the Cr32 gene of Cowdria ruminantium.
AB  - Cowdria organisms were purified by density gradient centrifugation. The DNA was
      used to construct expression libraries. The immunodominant Cr32 protein was
      purified and its N-terminal amino acid sequence was determined. The expression
      libraries were screened with Cr32-specific monoclonal antibodies, but did not
      yield Cr32-positive clones. Therefore a part of the Cr32-gene was amplified using
      primers derived from the N-terminal and an internal amino acid sequence. This DNA
      was used as a probe to detect the genomic DNA fragment encoding the Cr32 protein.
      This fragment was cloned, using genomic DNA of the Senegal strain of Cowdria
      ruminantium. A part of the gene comprising two third of its total length has been
      expressed in vector pGEX2T. This expression product is recognized by Cr32
      specific monoclonal antibodies.

PMID- 8134628
TI  - Seroconversion to Cowdria ruminantium of Malawi zebu calves, reared under
      different tick control strategies.
AB  - The seroconversion by indirect ELISA to Cowdria ruminantium over the first year
      of life of sixty-six Malawi zebu calves born into groups which were dipped 17
      times per year was compared to seroconversion of 32 calves born into non-dipped
      groups. Amblyomma variegatum tick counts and clinical disease in each group of
      cattle were monitored throughout the study period. No cases of heartwater were
      seen in either group of calves over the first 22 months of life. Only one case of
      heartwater was observed, in an 8 year old cow, in the 1,800 intensively monitored
      cattle over the same period. By 12 months of age almost all undipped calves had
      seroconverted and 50% of seroconversions were attributed to nymphal challenge. In
      contrast, only 41% of calves had become seropositive by 12 months of age in the
      dipped groups. The dipping regime used therefore significantly decreased
      seroconversion rates to C. ruminantium in these calves. 73% of calves had
      detectable levels of maternal antibodies to C. ruminantium in the first 4 weeks
      of life. Antibody levels in each of the calves in dipped groups had waned to
      below the cut off point for the ELISA by 8-12 weeks. Seroconversion did not occur
      in the first 8-12 weeks of life in dipped herds. The indirect ELISA test results
      were not significantly different in the proportion positive in single tests at 12
      months of age, or by cumulative test results of the previous 9 months, and
      therefore the test may be of value as a test of herd immunity.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8134629
TI  - Cowdria ruminantium identified in Amblyomma gemma using a DNA probe pCS20.
AB  - Amblyomma gemma ticks were collected from wild animals on a 20,000 acre game
      ranch in a heartwater endemic area in Kenya, close to Nairobi. A. variegatum is
      the main vector of heartwater in Kenya. E.A. LEWIS, 1947, in a one sentence
      report has implicated A. gemma to be a vector of heartwater without giving any
      details. Adult A. gemma were collected from giraffe Giraffa camelopardalis,
      hartebeest Alcephalus busephalus, Eland Taurotragus oryx and ostrich Struthio
      camelus during cropping exercises. The unengorged ticks were fed on 3 susceptible
      Dorper sheep which were monitored daily for the clinical symptoms of heartwater.
      All the ticks, including those that were fed on sheep were dissected and the guts
      probed for the presence of Cowdria ruminantium using a cloned DNA probe, the
      pCS20. None of the sheep on which the ticks were fed showed heartwater symptoms
      up to 60 days from the attachment of the ticks. The DNA probe identified Cowdria
      ruminantium in the ticks collected from eland and giraffe.

PMID- 8134630
TI  - Development and transmission of Cowdria ruminantium by Amblyomma males
      transferred from infected to susceptible sheep.
AB  - Male Amblyomma sp. were tested as vectors of Cowdria ruminantium, causative agent
      of heartwater disease. The males were allowed to feed on sheep experimentally
      infected with C. ruminantium and then were transferred to susceptible sheep to
      test for transmission of the rickettsia. The experiments were done in two trials.
      In the first trial, A. hebraeum were exposed to the Palm River stock of C.
      ruminantium, while in the second trial the Kiswani stock of Cowdria was tested
      with A. variegatum. Ticks were collected daily throughout each experiment, cut in
      half, and processed for light and electron microscopy to study development of C.
      ruminantium in tick tissues. In both trials, the male ticks transmitted Cowdria
      to one of two susceptible sheep. When ticks were examined with microscopy, a few
      colonies were found in gut cells while none were seen in salivary glands. Both
      species of ticks were infected with Rickettsia conorii, as evidenced by the
      occurrence of rickettsiae in the nucleus and cytoplasm of salivary gland cells.

PMID- 8134631
TI  - Inhibition of Cowdria ruminantium infectious yield by interferons alpha and gamma
      in endothelial cells.
AB  - We have shown before that there is a positive correlation between resistance of
      cattle against Cowdria infection and early IFN production. Our in vitro studies
      demonstrated an activity of rBoIFN alpha 2C and rBoIFN gamma against Cowdria in
      bovine endothelial cells of brain microvasculature (BMEC). rBoIFN gamma is much
      more active in this respect than rBoIFN alpha 2C. These results suggest a role of
      IFNs in the resistance against the disease. Strikingly, in the same conditions
      rBoIFN alpha 2C has no effect on the yield of Cowdria from infected bovine
      endothelial cells of umbilical artery origin (BUEC). Similarly we showed that
      HuIFNa had no effect on the multiplication of Cowdria in human vein umbilical
      endothelial cells (HUVEC). We found no differences in the capacity of BUE and BME
      cells to bind rBoIFN alpha 2C. This may reflect a true difference between
      capillary and large blood vessels.

PMID- 8134632
TI  - The development of antibody to Cowdria ruminantium in mice and its role in
      heartwater disease.
AB  - DBA/2 and Balb/c mice were used as a model to study the immune responses to
      Cowdria ruminantium. Both strains of mice were inoculated with 1, 10 or 100 LD50
      of the Crystal Springs strain of C. ruminantium. Antibody to C. ruminantium
      started to develop in the second week post-inoculation and the titre of the
      antibody was dependent on the inoculation dose of C. ruminantium. The possible
      role of antibody in heartwater disease was studied by in vitro neutralization
      assays using both mouse sera and bovine sera. Results of these tests show that
      hyperimmune serum from both DBA/2 and Balb/c mice had the ability to neutralize
      infection in vitro, with the DBA/2 serum showing a greater neutralizing effect.
      Two bovine sera, one from a laboratory infected animal and one a pool from two
      animals infected in the field also gave a neutralizing effect.

PMID- 8134633
TI  - Occurrence of caprine leucocyte antigens (CLA) in Creole goats
      susceptible/resistant to heartwater.
AB  - A genetic predisposition to the manifestation of disease symptoms has been
      demonstrated for heartwater in certain goat lines. In order to clarify a possible
      involvement of the major histocompatibility complex (MHC) in the pathogenesis of
      heartwater, over 100 Creole goats have been typed serologically for their CLA
      class I antigens coded by the caprine MHC. The MHC is a genetic system that
      influences different immunological processes, i.e. the individual immune
      response. With our alloantisera we were able to detect 13 different CLA alleles
      also present in the Swiss breeds, two non-MHC antigens, a new cluster defined by
      the splitting of two antigens and several specific reaction patterns of single
      reagents. The allele frequencies of the detected CLA antigens differed for the
      resistant and susceptible groups examined. Whether the differences represent
      regional sire effects or indicate pathogen-induced selection pressure remains to
      be clarified. Additional testing of resistant/susceptible goats originating from
      common environment as well as of specially crossbred (resistant x susceptible)
      animals are underway.

PMID- 8134634
TI  - Use of serological response to evaluate heartwater immunization of cattle.
AB  - Frozen blood vaccine containing the Ball 3 strain of Cowdria ruminantium is
      prepared by an FAO/DANIDA Project in Malawi for the immunization of improved
      dairy cattle against heartwater. The immunogenicity of vaccine batches for cattle
      has been quantified and different regimens for immunization have been evaluated
      using indirect immunofluorescence to assess antibody responses. Infected
      endothelial cells grown in culture are used as antigen. The proportion of animals
      responding serologically has varied between different batches of vaccine tested
      in homogeneous cattle populations at the same time, presumably reflecting
      differences in immunogenicity of batches. The proportion of animals in a
      homogeneous population responding serologically to the same vaccine batch
      administered under different regimens has also varied. Indirect
      immunofluorescence testing has proved to be a useful method for assessing the
      immune response of cattle to immunization and has been adopted as a routine
      quality control procedure for heartwater vaccine production in Malawi.

PMID- 8134635
TI  - Cowdriosis in Senegal: some epidemiological aspects.
AB  - The results of a study on the abundance of Amblyomma variegatum in different
      ecological zones and of Cowdria ruminantium infection rates in nymphal and adult
      ticks of the North Guinean zones are given. Joint research is also conducted on
      the evaluation of seroprevalence. In this study, it appears that the vector is
      most important in the North Guinean zone, followed by the South Sudan and the
      coastal Niayes zones. Elsewhere, the tick populations are not significant or
      absent. The infection rate in the North Guinean zone is high: 1.1% at least for
      adult ticks and 7.8% for nymphs. The seroprevalence in the North Sudan and the
      Sudano-Sahelian zones is very low in the hinterland whereas the values are higher
      near the coast.

PMID- 8134636
TI  - Vaccination against heartwater using in vitro attenuated Cowdria ruminantium
      organisms.
AB  - Sequential passage of Cowdria ruminantium (Senegal isolate) in cultures of bovine
      umbilical endothelial cells has resulted in loss of virulence without loss of
      immunogenicity, as previously demonstrated. We have carried out further
      immunization of 39 Dutch sheep using in vitro attenuated rickettsiae of passage
      21 and challenged these animals either with the homologous or with heterologous
      Cowdria stocks. After vaccination several sheep developed elevated rectal
      temperatures for a maximum of 2 days, but no further clinical response to the
      vaccine was observed. All sheep developed high titres of antibodies to Cowdria.
      Challenge of 10 sheep with the homologous virulent stock did not provoke any
      clinical reaction, demonstrating that these animals were solidly immune.
      Reactions to heterologous challenge varied from virtually no reaction to fatal
      heartwater depending on the stock of Cowdria used. These results are discussed in
      relation to currently available vaccination methods against cowdriosis. In
      Senegal 30 susceptible sahelian sheep were immunized with attenuated rickettsiae
      of passage 21. Hyperthermia was seen in 13, the only other clinical symptom was a
      temporary diarrhoea. The immunized animals are at present exposed, together with
      30 controls, to field challenge in the Niayes, the area where the Senegal isolate
      was originally isolated.

PMID- 8134637
TI  - Simulation of infestation risk of cattle by gastro-intestinal trichostrongylids
      in a tropical humid climate.
AB  - The population dynamics of trichostrongylid third stage larvae (L3) around bovine
      dung were fitted with non-linear models (marginal law) in tropical humid climate
      in different climatic situations. These marginal models were combined with the
      survival duration of pats, the weight of cows, the number of pats per cow and per
      day, the stocking rate and the herbage mass availability, taking into account the
      patchy grazing behaviour of cattle in order to estimate infestation probability
      of cattle by third stage larvae. The infestation risk was computed for different
      ages of herbage regrowth and grazing times in rotational grazing systems. The
      infestation risk was found to range between 0 to 1400 L3 per kg of dry matter of
      grass and per day depending on the marginal law. The grazing time, the age of
      herbage regrowth and the forage availability were the main factors of variation
      of the infestation risk.

PMID- 8134638
TI  - Progress towards a vaccine against Theileria parva: relevance for heartwater
      research.
AB  - Such progress has been made in the last decade in the characterization of bovine
      immunity to Theileria parva. The evidence is overwhelming that cattle that become
      immune through infection can clear subsequent challenge infections by deploying
      parasite-specific cytotoxic T lymphocytes (CTL). Furthermore, high titres of
      neutralising antibodies are generated against the sporozoite surface after
      multiple exposure to the parasite, and these can neutralise infection in vitro.
      Although unlikely to be of relevance under natural circumstances, the latter
      observation has been exploited to generate a promising candidate neutralising
      vaccine based on a recombinant form of the major surface antigen of the T. parva
      sporozoites. Efforts are under way to identify the target antigen(s) of T. parva
      specific CTL, and when this has been achieved, an improved vaccine targeted on
      both infective and pathogenic stages of the parasite will be within reach. The
      elucidation of the basis of immunity of ruminants to Cowdria ruminantium, the
      causal agent of heartwater, is at a comparatively early stage. However, many of
      the principles and techniques that have led to the current understanding of the
      immunology of T. parva are already being applied to heartwater, and these should
      enable rapid progress to be made in the development of a vaccine against C.
      ruminantium.

PMID- 8134639
TI  - The tick vectors of cowdriosis in Angola.
AB  - Amongst the Amblyomma species presently known to be capable of transmitting
      Cowdria ruminantium six have been recorded in Angola. A. pomposum is the most
      important and widely distributed. Of secondary importance are A. variegatum,
      which prevails in Cabinda and Moxico provinces, and A. astrion which occurs in
      the littoral and transition strips and on Camabatela plateau. A. sparsum and A.
      tholloni which are specific parasites of wild hosts are considered accidental
      vectors. A. hebraeum was introduced recently in the territory but its
      distribution is unknown at present. For each of these species the hosts,
      distribution, ecology and seasonal abundance are listed.

PMID- 8134640
TI  - Experimental dermatophilosis in murine models of immunodeficiency.
AB  - Gnotobiotic mice with congenital immune deficiencies were infected with the skin
      pathogen Dermatophilus congolensis. Athymic (nude) mice with T cell deficiency
      were less susceptible than nude mice which also carried the beige mutation (beige
      nude) with NK cell and granulocyte defects, as part of the murine equivalent of
      Chediak-Higashi syndrome. The additional presence of the x-linked
      immunodeficiency gene in other beige mutant mice, giving reduced B cell
      responsiveness, did not increase their susceptibility. BALB/c mice with the nude
      mutation and evidence of macrophage insufficiency, had a moderate level of
      susceptibility, greater than that of outbred nude mice but less than that of
      beige, nude mice. The appearance of the lesions on the haired mice was different
      from that on those with hairless skin (nude and beige-nude). On the haired mice
      thin crusts developed and healed rapidly, while on the hairless mice the lesions
      started as nodules and later progressed to crusts. The nude BALB/c mice developed
      atypical lesions, which resembled ulcers. Germ-free nude and beige-nude mice
      showed the same types and time course of infection as the gnotobiotic animals,
      suggesting that bacterial interference, by a limited skin flora, did not play a
      major role in defence against D. congolensis. However, bacteriological analysis
      indicated that D. congolensis could survive in the gut of germ-free mice. This
      work emphasizes the importance of non-specific immune mechanisms, such as
      epidermal hyperproliferation and the neutrophil, in resistance to D. congolensis.

PMID- 8134641
TI  - A survey of goat and cattle diseases in the Artibonite Valley, Haiti, West
      Indies.
AB  - A 40 week study of 43 farmers, 60 goats and 60 cattle was conducted in order to
      identify abnormal conditions or diseases and predisposing seasonal, managemental
      or nutritional factors. Farms were visited, farmers interviewed and animals
      examined up to 4 times, about every 10 weeks, and bled for Ht, total WBC,
      selected serum vitamins and minerals, hair collected for mineral analysis. Soil
      and forages were collected for analysis. Animals were generally in fair
      condition, with poor growth and reproduction. Unexpected wet season caloric
      deficiency, severe P deficiency and lesser vit. A and E deficiencies were noted.
      Anaemia, secondary to parasitism, was common to both species, worse in goats.
      Cattle had ticks, while goats had lice. Goats had reported neonatal diarrhea and
      mortality; observed exfoliative dermatitis, warts, dermatophytosis and possible
      contagious ecthyma. Cattle had reported anthrax and babesiosis; observed
      vesicular vaginitis, orchitis and teat warts.

PMID- 8134642
TI  - Cellular responses in experimental chronic and acute dermatophilosis infections
      of sheep.
AB  - The cellular infiltrate into the dermis in dermatophilosis lesions is composed of
      a range of cell types. The aim of this study was to establish if the composition
      of the cellular infiltrate in chronic lesions was different from that in healing
      lesions. Experimental Dermatophilus congolensis infections of sheep were used to
      study the sequential changes in cell types during the course of chronic and acute
      infections. Infestations of adult Amblyomma variegatum ticks were used to produce
      chronic lesions on infected sheep, infections of tick-free sheep provided acute
      lesions. Histopathology and immunohistochemistry were used to stain and label
      cell types in the dermis of infection sites. Neutrophils dominated the early
      response and were present in larger numbers in chronic lesions. Plasma cells were
      present in both types of lesion, however they persisted in chronic lesions but
      disappeared from the skin at acute lesion sites after the lesions had resolved.
      There were 2-3 times as many mononuclear cells in chronic than acute lesions from
      as early as 4 days post infection and these cells persisted in the chronic
      lesions. In the chronic lesions the mononuclear cell population was composed of T
      helper and T-cytotoxic/suppressor lymphocytes in equal proportions whereas in
      acute lesions at 14 days post infection, when lesion resolution is underway,
      there were greater numbers of T-helper cells than T-cytotoxic/suppressor cells.

PMID- 8134644
TI  - An attempt to identify genetic markers of resistance or susceptibility to
      dermatophilosis in the zebu Brahman population of Martinique.
AB  - Dermatophilosis is a disease associated with the tick Amblyomma variegatum, and a
      genetic predisposition to the manifestation of symptoms has been demonstrated.
      Indeed, the Creole cattle of Guadeloupe constitute a population which is highly
      resistant to this disease, whereas the Brahman zebu cattle of Martinique seem
      very susceptible. However, in this Brahman population there is a gradient
      regarding the severity of symptoms depending on individuals. In several herds of
      these pure zebu Brahman, kept under the same farming conditions, we selected
      susceptible and resistant groups because of the simultaneous presence of animals
      affected or not by clinical dermatophilosis. In these animals we studied several
      highly polymorphic genetic systems such as haemoglobin, albumin, the BoLA Complex
      (class I and II) and the gamma S crystallin gene. Only exon 2 of the BoLA-DRB3
      gene, investigated by PCR-RFLP technique, showed interesting polymorphisms. We
      have established a genotypic map showing at least 4 different alleles of which 1
      seems particular to one animal susceptible to dermatophilosis. Before reaching
      any conclusion further investigations with more DNA samples of susceptible
      animals are needed.

PMID- 8134643
TI  - An attempt to correlate cattle breed origins and diseases associated with or
      transmitted by the tick Amblyomma variegatum in the French West Indies.
AB  - By using biological data and historical research, we have tried to explain the
      difference between resistance and susceptibility to the diseases transmitted
      (cowdriosis) or associated (dermatophilosis) with the tick Amblyomma variegatum,
      in two cattle breeds of the French West Indies: the Creole crossbred cattle of
      Guadeloupe and the Brahman zebu cattle of Martinique. Have been studied the
      polymorphisms of 5 independent genetic systems (erythrocytic haemoglobin, serum
      albumin and transferrin, the class I region of the BoLA complex and the gamma S
      crystallin gene) in different breeds comprising Bos taurus cattle of Europe and
      Africa, Bos indicus of West and East Africa, as well as the Brahman of Martinique
      and the Creole crossbred of Guadeloupe. By comparing the different allele
      frequencies of these 5 non related polymorphic loci and by using the two
      different mathematical matrices of NEI and of CAVALLI-SFORZA, have been
      established the genetic distances between these breeds. It appears clearly that
      the Creole cattle of Guadeloupe are in an intermediate position between the Bos
      taurus N'Dama breed of West Africa and two Bos indicus zebu breeds, namely the
      West African Sudan zebu and the Brahman. Thanks to studies of different archieves
      in the Caribbean and in Europe, historical evidence have been accumulated on the
      geographical origins and on the chronology of the establishment of Creole and
      Brahman cattle in the French West Indies. The high resistance of the Creole
      cattle of Guadeloupe to diseases associated with or transmitted by the
      "Senegalese" tick Amblyomma variegatum seems to be due to the inheritance of a
      pool of genes from West African cattle and more particularly from the N'Dama
      breed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134645
TI  - Observations on a dermatophilosis outbreak in Brahman cattle in Guadeloupe.
      Description, epidemiological and economical aspects.
AB  - A severe outbreak of dermatophilosis occurred in 1985 in a herd of Brahman cows
      imported from Martinique in Guadeloupe in July 1983. Little was known on this
      disease in Guadeloupe until then, for the local zebu breed is naturally highly
      resistant to diseases transmitted by ticks or associated with them. Conditions of
      appearance and development of the disease were studied in relation with herd
      management, climate and treatments applied. There was no evidence of the disease
      during the first 6 months following the importation, in a feedlot management. The
      first lesions of dermatophilosis appeared about 2 months after the animals were
      allowed to graze on pastures infested with ticks. Then, thirty percent of the
      herd became infected. Development of the infection increased dramatically as the
      humid season approached, and all the 29 Brahman cows showed lesions in July 1985.
      Only drastic treatments, including antibiotics and local disinfection, associated
      with the removal from pastures into covered stables allowed the recovery from the
      disease. Nevertheless, the disease caused the death of 13 head. Differences in
      individual reactions were also noted, and 7 different types of evolution were
      identified. These observations provided informations about the epidemiology of
      dermatophilosis in the climatic conditions of Caribbean humid tropics. They
      showed the economic importance of this severe disease for cattle in the region
      and the sensitivity of exotic breeds.

PMID- 8134646
TI  - Study of efficacy of Lamstreptocide A & B on cases of dermatophilosis within the
      Caribbean.
AB  - The efficacy of Lamstreptocide A & B was studied on 9 natural cases of bovine and
      caprine dermatophilosis in 8 different farms in St. Kitts, employing standard
      histopathologic and bacteriological methods. The lesions of 5 of the treated
      cases were dried-up, and there was marked peeling-off of scabs of a severely
      affected case exposing erythematous underlying tissue, at 3 weeks post
      application of the product. Apart from 3 mild cases which were not available for
      follow-up studies and which were reported to have recovered, there was no
      outright recovery of the 5 animals after treatment at 3 weeks, and even after a
      second application of the product. An in vitro sensitivity test of the product
      revealed a slowing down of growth of Dermatophilus congolensis at concentrations
      in excess of 1% by agar-streak method. However, there was no inhibition of growth
      of the bacterium by an agar-impregnated sensitivity method.

PMID- 8134647
TI  - The epidemiology and control of camel dermatophilosis.
AB  - Camel dermatophilosis was only recently described. It appears however that it is
      more widespread than originally thought. In Kenya it has generally been found in
      the main semi-arid camel rearing areas of Samburu and Laikipia districts although
      it has not yet been found in the arid areas of Turkana district. In an
      investigation of ticks on 200 camels, no Amblyomma variegatum ticks were found
      although many other ticks were present. A. variegatum is suspected to transmit
      dermatophilosis in many domestic animals. The only control method of
      dermatophilosis currently practised in Kenya is in one commercial farm, where
      camels are regularly washed with a 1% potassium aluminium sulphate solution. The
      camels have shown progressive improvement. Recently, some 50 camels imported from
      Pakistan in this farm came down with a severe skin infection which closely
      resembled dermatophilosis. All imported adult camels were involved although no
      calves were involved. Since no bacteria were isolated from all the sick camels,
      it was thought to be due to vitamin deficiency.

PMID- 8134648
TI  - The systemic effect of adult and immature Amblyomma variegatum ticks on the
      pathogenesis of dermatophilosis.
AB  - The systemic effect of adult and nymphal Amblyomma variegatum on the pathogenesis
      of experimental infections of Dermatophilus congolensis was investigated. Three
      groups of four sheep were used with all 12 sheep being infected with identical
      titrated doses of D. congolensis One group of sheep was simultaneously infested
      with adult A. variegatum the second with nymphal A. variegatum and the third
      group were the controls, with no exposure to ticks. Assessment of the resulting
      infections indicate that the systemic effect of this tick is confined to the
      adults. Skin and serological tests using foreign antigens showed significantly
      reduced cell mediated and humoral immune response only in the sheep infested with
      adult A. variegatum.

PMID- 8134649
TI  - The effect of tick control on the prevalence of dermatophilosis on indigenous
      cattle in Ghana.
AB  - The effectiveness of three tick control regimes on the occurrence of Amblyomma
      variegatum and dermatophilosis on cattle on the coastal plains of Ghana were
      compared. Animals at one kraal were sprayed with amitraz at predilection feeding
      sites of ticks every second week using a high concentration minimum volume
      technique. Animals at two other kraals were treated with a deltamethrin based
      pour-on acaricide; at one kraal it was applied once every month while at the
      other kraal it was used at strategic times based on the expected seasonal
      increases in the level of infestation with A. variegatum. Animals in a fourth
      kraal (control group) were treated, by the herdsmen, to control excessive tick
      build-up as practised under traditional management systems. Fortnightly treatment
      with amitraz reduced the level of infestation with A. variegatum and the
      prevalence of dermatophilosis dropped to a low level. The pour-on acaricide
      similarly depressed the prevalence of dermatophilosis.

PMID- 8134651
TI  - Variability of cattle infestation by Amblyomma variegatum and its possible
      utilisation for tick control.
AB  - A great variability of the individual infestation by Amblyomma variegatum adults
      was observed on naturally infested Gudali zebus. Some of the animals (called
      "attractive for A. variegatum") had a tick burden 10 to 16 times higher than that
      of the least parasitized cattle of the herd (called "non-attractive"). Ranking of
      the animals based on A. variegatum infestation was correlated for successive tick
      counts. Experiments were designed to determine if the "non-attractive" cattle
      remained lightly infested when the "attractive" ones are removed from the herd.
      When these two types of cattle grazed separately, it was observed that the "non
      attractive" animals had a lower tick burden and that their infestation occurred
      more slowly than that of the "attractive" ones. The difference between the two
      groups was nevertheless smaller than that existing when the animals were in the
      same herd. The selection of the "non-attractive" cattle, on which a tick control
      programme should not exclusively be based, could however be used as a component
      of a tick control strategy, if this characteristic is hereditary. An experiment
      in progress will study the question.

PMID- 8134650
TI  - Ventilation in the adults of Amblyomma hebraeum and A. marmoreum (Acarina,
      Ixodidae), vectors of heartwater in southern Africa.
AB  - The objective of this study was to establish the major features of respiratory
      gas exchange in unfed adults of the ticks Amblyomma hebraeum and A. marmoreum,
      both vectors of heartwater in Southern Africa. Carbon dioxide emission of ticks
      was measured at 25 degrees C using flow-through respirometry in order to
      determine standard metabolic rate (SMR) and the temporal pattern of gaseous
      emission. For both species, SMR was extremely low and approximately 100 fold less
      than that predicted for an insect of equivalent body mass. Ventilation in
      inactive ticks was discontinuous and characterized by periodic bursts of CO2
      emissions during spiracular opening. The main selective advantage of this type of
      ventilation is believed to lie in a reduction of respiratory water loss. The
      periodicity of CO2 bursts was less frequent in A. marmoreum (every 2.5 h)
      compared to A. hebraeum (every 1.5 h) suggesting that A. marmoreum is more
      efficient at conserving respiratory water loss. It is suggested that future
      research into water balance physiology of ticks should address the role of
      ventilatory patterns in determining off-host survival and habitat associations.

PMID- 8134652
TI  - Acaricides for eradication of the tick Amblyomma variegatum in the Caribbean.
AB  - The success of an eradication campaign against the tropical bont tick in the
      Caribbean imposes the use of active acaricide compounds, if possible with
      residual activity, easy to apply and requiring few or no accessible water
      supplies and expensive application equipment. Tests of in vitro susceptibility of
      tick strains from Puerto Rico and Guadeloupe as well as observations of the
      impact of the current tick control campaigns conducted in some Caribbean islands,
      seem to indicate that there is no problem of resistance to acaricides. Pyrethroid
      acaricides have an advantage since they are active at very low concentration
      levels and have a low toxicity for mammals and to the environment. Some of them
      are in a pour-on formulation which allows for rapid application and complete
      coverage of the whole body of the animal. A withdrawal period is not necessary.
      However, improvements must be found to facilitate the application onto the back
      of cattle that, for the majority in the Caribbean, are tethered and not perfectly
      restrained. A spot-on application method with a drench gun seems more adapted to
      tethered animals than the pour-on. For small ruminants and dogs but also for
      cattle, slow release devices impregnated with acaricides may be useful in
      reducing the frequency of animal treatments. However, experiments on goats with
      collars impregnated with flumethrin indicate an efficiency of less than 55 days,
      insufficient to justify their use on a large scale in an eradication program.

PMID- 8134653
TI  - Eradication of a new focus of Amblyomma variegatum in Puerto Rico.
AB  - In May 1992 an infestation with the tropical bont tick appeared in a small dairy
      heifer replacement herd in Camuy, Puerto Rico, a completely new site located near
      Puerto Rico's northwest coast. This finding occurred after some three years of no
      infestation in either Puerto Rico or the U.S. Virgin Islands and is not suspected
      of being associated with any previous infestations. The methods used to eradicate
      this tick include spray treatment at a two-week interval of all domestic
      livestock, with amitraz at 0.025% and permethrin at 0.055%. Dogs and chickens are
      also inspected. Owners are encouraged to reduce numbers of these species. All
      livestock on adjoining farms are inspected and treated on a frequent basis. There
      has been no evidence of any spread and the infestation is expected to be
      eliminated within 18 months.

PMID- 8134654
TI  - Progress towards a program for the eradication of Amblyomma variegatum from the
      Caribbean.
AB  - Amblyomma variegatum (Fabricius), the tropical bont tick, is now widely
      distributed in the Caribbean. Eighteen islands countries are now or were recently
      infested with the tick. To stop the spread of this tick to other non-infested
      islands and to the mainland areas of South, Central and North America, a regional
      eradication program has been proposed and endorsed by the respective governments
      on each of the Amblyomma variegatum infested islands, including the French
      government and CARICOM member and associate member countries. The Food and
      Agriculture Organization of the United Nations (FAO) was requested by CARICOM, on
      behalf of member and associate member governments to: develop eradication
      proposals; assist CARICOM member countries to maintain existing Amblyomma tick
      control programs; advise and assist with the drafting of legislation required for
      implementation of an eradication program; assist in the identification of funds
      to implement the eradication program and, if funding was obtained, coordinate the
      eradication campaign against this tick on all infested islands. The current
      distribution of the tick and the status of the proposed eradication program in
      the Caribbean are discussed.

PMID- 8134655
TI  - The relationship of Haitian small farm management to goat and cattle diseases.
AB  - A 40 week study of 43 farmers, 60 goats and 60 cattle was conducted in order to
      identify abnormal conditions or diseases and predisposing seasonal, managemental
      or nutritional factors. Farms were visited, farmers interviewed and animals
      examined up to 4 times, about every 10 weeks and bled for Ht, total WBC, selected
      serum vitamins and minerals hair collected for mineral analysis. Soil and forages
      were collected for analysis. There were serious soil, forage and animal
      phosphorus and lesser vitamin E and A deficiencies due to a lack of appropriate
      soil fertilization, and/or dietary insufficiency. Presumptive parasitic anaemia
      was a common clinical sign in goats (43% incidence) and in cattle (19%
      incidence). Infectious diseases, external and internal parasitism were partially
      controlled by animal isolation, movement and tethering, rarely by therapeutics.
      Overall, livestock condition was fair, reproductive and growth performance poor,
      but catastrophic disease rare. Ruminant feeding was entirely from scavenging of
      crop residues for human consumption, or voluntary plants. Given the scarcity
      and/or high cost of forages, fertilizer, vitamin-mineral supplements, drugs and
      vaccines, the present system of Haitian small farm management is successful in
      catastrophic disease prevention, but is inefficient for minor diseases,
      reproduction and growth.

PMID- 8134656
TI  - Persistence of tick-derived Anaplasma marginale in cultured bovine turbinate and
      endothelial cells.
AB  - Anaplasma marginale from salivary glands of Dermacentor andersoni was used to
      inoculate monolayers of bovine turbinate and endothelial cells. Monolayers were
      passaged at 2 or 4 week intervals and monitored with light and electron
      microscopy and with an A. marginale-specific DNA probe. Intracellular inclusions
      were observed in turbinate cells after 2-4 weeks. The number of inclusion-bearing
      cells increased over 1-2 weeks and gradually disappeared. A radiolabeled fragment
      from within the msp1 beta gene of the erythrocytic stage of A. marginale
      hybridized to DNA extracted from bovine turbinate cell cultures as late as 7
      weeks post inoculation (passage 4). Individual rickettsiae were observed with
      electron microscopy in samples taken at this time. Susceptible calves inoculated
      with suspect cultures did not develop clinical anaplasmosis but did develop
      significant antibody titers as detected with ELISA. DNA from endothelial cell
      cultures at 9 weeks post inoculation also bound the Anaplasma-specific DNA probe.
      Anaplasma marginale from salivary glands of D. andersoni appears to persist in
      cultured bovine turbinate and endothelial cells but typical development and
      infectivity for bovines do not occur.

PMID- 8134657
TI  - Ovine trypanosomosis: a seroepidemiological survey in coastal Guyana.
AB  - The objective of this study was to determine the seroprevalence rates of
      Trypanosoma vivax and Trypanosoma evansi in sheep in coastal Guyana. Blood
      samples were taken from a systematic random sample of one hundred and ninety
      three (193) sheep on twenty-two (22) farms in Region 5, Mahaica/Berbice, a
      coastal area of Guyana. Age, breed, sex, and farm of origin were recorded for all
      sampled sheep. One hundred and seventy-six (176) serum samples were submitted for
      Indirect Fluorescent Antibody (IFA) testing for T. vivax and T. evansi.
      Fluorescence was graded as 0 (negative), 1+(very weak), 2+(weak), 3+(strong) or
      4+(very strong), measured at 1:160 dilution of serum. Samples were considered to
      be sero-positive if any fluorescence was observed. Indirect Fluorescent Antibody
      results were received for one hundred and sixty-one (161) samples. One hundred
      and three (64%) sera were sero-positive for Trypanosoma sp. Of these, 38 (23.6%)
      sera were positive to T. evansi only, 11 (6.8%) were positive to T. vivax only
      and 54 (33.5%) were positive for both. As cross reactions occur between T. vivax
      and T. evansi, it was difficult to determine the true species of exposure for the
      sera which tested positive to both species. The overall sero-prevalence rate of
      64% suggests that trypanosomosis is endemic in sheep in coastal Guyana. This was
      the first serological evidence of T. evansi in Guyana. Although T. vivax is
      believed to be pathogenic in sheep, the clinical significance of T. evansi
      remains unknown. The vector of both species of trypanosomes in sheep on the north
      coast of South America also is not known.

PMID- 8134658
TI  - Serological evidence for the presence of Brucella antibodies in sheep and goats
      on Saint Croix, U.S. Virgin Islands.
AB  - A serological survey for Brucella antibodies in sheep and goats was completed on
      Saint Croix, United States Virgin Islands (USVI). Seroprevalence (at suspect or
      reactor titer levels) for B. melitensis antibodies was 11.3% for sheep and 2.5%
      for goats. This is the first report, of which we are aware, of B. melitensis
      antibodies in sheep or goats in the Caribbean islands.

PMID- 8134659
TI  - Use of multiplex polymerase chain reaction-based assay to conduct epidemiological
      studies on bovine hemoparasites in Mexico.
AB  - A study was conducted to test the applicability of a Polymerase Chain Reaction
      (PCR)-based approach for the simultaneous detection of the bovine hemoparasites
      Babesia bigemina, B. bovis and Anaplasma marginale. Bovine blood samples from
      cattle ranches of a previously determined enzootic zone in the Yucatan Peninsula
      of Mexico, were collected from peripheral blood and processed for PCR analysis.
      Blood samples were subjected to DNA amplification by placing an aliquot in a
      reaction tube containing oligonucleotide primers specific for DNA of each
      hemoparasite species. The PCR products were detected by Dot-Blot nucleic acid
      hybridization utilizing nonradioactive, species-specific, digoxigenin PCR-labeled
      DNA probes. Four hundred twenty one field samples analyzed by the multiplex PCR
      DNA probe assay showed 66.7%, 60.1% and 59.6% prevalence rates for B. bigemina,
      B. bovis and A. marginale, respectively. The multiplex PCR analysis showed that
      animals with single, double or triple infection could be detected with the
      parasite specific DNA probes. The procedure is proposed as a valuable tool for
      the epidemiological analysis in regions where the hemoparasite species are
      concurrently infecting cattle.

PMID- 8134660
TI  - Recommendations for African horse sickness vaccines for use in nonendemic areas.
AB  - African horse sickness (AHS), which causes mortality up to 95%, is caused by
      orbiviruses and is transmitted by Culicoides. The goal of a control and
      eradication program for AHS is to prevent the spread of the virus via the
      biological vector. Control measures include slaughter of infected animals,
      housing of suspected infected animals in insect-proof stalls, and vaccination.
      Vaccination has played a key role in eradication when AHS occurred outside of
      Africa. Both modified live vaccines (MLV) and inactivated vaccines have been used
      to control AHS. An acceptable vaccine should be: safe, efficacious, and
      available. The vaccine should not cause disease or viremia, and the vaccine virus
      should not revert to a virulent virus upon backpassage in susceptible Equidae.
      The vaccine should protect against death and clinical signs and, most
      importantly, should prevent viremia in vaccinated Equidae following exposure to
      virulent AHS virus. The challenge inoculation system for assessing immunity to
      AHS is discussed. The vaccine should be readily available, implying that it is
      either in routine production in facilities that meet internationally accepted
      guidelines for biological production facilities or in a vaccine bank. Banking of
      cryopreserved stocks of MLV or concentrates of inactivated vaccines is a means of
      having AHS vaccine available for future epizootics. A recently developed
      diagnostic test to differentiate vaccinated from naturally infected animals
      provides regulatory officials with useful information for the control of AHS.

PMID- 8134661
TI  - Immunization of dogs with Q fever vaccines: comparison of phase I, II and phase I
      CMR Coxiella burnetii vaccines.
AB  - Q fever vaccines were tested in mixed breed dogs by vaccinating them with
      formalin-killed Coxiella burnetii whole cells (WC) in either phase I (WCI) or
      phase II (WCII), or the chloroform: methanol residue (CMR) subunit of phase I
      cells. Phase I vaccines mixed (1:1) with Freund's incomplete adjuvant (FIA)
      induced humoral immune responses to phases I and II antigens as measured by
      microagglutination assay. The CMR vaccine mixed (1:1) with FIA induced greater
      antigen-specific antibody levels to both phases I and II antigens than the
      corresponding WCI vaccine. The WCII vaccine induced antibody responses to only
      phase II antigens. The time course of erythema and induration after skin testing
      with C. burnetii antigens were suggestive of cell-mediated immunity (CMI).
      Although granulomas were observed with only WCI and WCII, none of the skin test
      antigens induced abscesses at the injection site. In contrast, axillary nodes
      draining the vaccine injection site developed sterile draining abscesses in all
      dogs by days 19 to 24 for the WCI and CMR, and day 104 for the WCII vaccines. The
      abscesses had resolved within 30 days after first appearance. Responses to Con A
      and PHA and recall antigens of lymphocytes from the blood, axillary and
      mesenteric nodes, and spleen at 222 days after vaccination were variable among
      dogs. Lymphocytes from various organs responded to one or more of the recall
      antigens and to both mitogens in the absence or presence of indomethacin.
      Although these Q fever vaccines induced humoral and CMI, either the antigens or
      FIA caused sterile draining abscesses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134662
TI  - [Factors associated with a 1-year development in the functional autonomy of
      elderly persons living at home].
AB  - The purpose of the study was to examine the incidence and reversibility of
      disability among elderly people over one year follow-up and to determine the
      predictors of functional changes. The population used in this analysis consisted
      in 1850 subjects aged 65 and over included in the PAQUID cohort and visited again
      at one year follow-up. Disability was measured by Katz's scale (Activities of
      Daily Living or ADLs), Lawton's scale (Instrumental Activities of Daily Living or
      IADLs) and a mobility scale. The one year incidence of the dependency was 5.6%
      for ADLs, 10.8% for IADLs, and 3.3% for mobility. Being dependent at baseline was
      associated with an increased risk of one year mortality comprised between 3.3 and
      5.3 according to the measurement scale. Recovery back to independence was
      frequent however, especially for ADLs (44.7%) and mobility (28.9%). Predictors of
      disability were: age in all scales, vision impairment and Mini Mental State
      Examination score for IADL and mobility scales, depressive symptomatology for
      ADLs, female sex and breathlessness for IADLs. Absence of cognitive impairment at
      baseline was associated with recovery to independence in all scales.

PMID- 8134663
TI  - [Economic evaluation of screening for neuroblastoma].
AB  - Though neuroblastoma, a cancer occurring in children, is infrequent, several
      countries run screening programs to detect it early since advanced stages show
      high mortality rates. The aim of this study is to propose a non empirical medico
      economic evaluation model for the screening program for neuroblastoma, adaptable
      to various contexts. A marginal cost-effectiveness analysis was performed. The
      effectiveness and cost criteria were respectively the number of children who do
      not die from neuroblastoma and the cost of the screening programs, together with
      the cost of the treatments. The major parameters of the model were: size of
      target population, incidence, over-incidence rate, compliance rate, test
      sensitivity, distribution of cases and mortality rates according to the stage of
      the disease. The aim of the model was to determine, within a specific context
      (fixed parameters), the cost of an additional life saved, or less pragmatically
      to calculate the threshold values for the parameters for which the screening
      program for neuroblastoma is worthwhile (ie marginal cost equal to zero). We
      illustrate this model presentation with simulations elaborated from the
      neuroblastoma screening program performed in the Rhone area, France.

PMID- 8134664
TI  - [Experience in mass screening of breast cancer with mammography in France].
AB  - In the framework of the National Fund for Prevention, Health Education and
      Information, the setting-up in France, on an experimental basis, of mass breast
      cancer screening programs by mammography in ten departments leads to suggest a
      common protocol for the evaluation of these programs, before an eventual
      generalization to the whole country. These programs are based on common
      principles: local screening based on existing medical facilities, single view
      mammography with double reading. However, the screening organisation is different
      in each department according to the target population, the screening interval,
      the mode of invitation, the methods for arranging double reading, etc. The
      purpose of this article is to report on the work of the evaluation group of the
      ten programs, and to propose a methodology for comparing the screening
      experiences in order to measure the role of the organisation methods. It gives
      definitions and modes of calculations for the evaluation criteria in four fields:
      impact, quality, efficacy and cost (with details about the feasibility of data
      collection) and proposes a reflection on analysis techniques in order to develop
      an optimum mass screening strategy.

PMID- 8134665
TI  - [Incidence of and factors associated with primary cesarean section in Benin
      (Africa)].
AB  - Among 3225 deliveries in two Cotonou public maternity units, 244 primary cesarean
      section were observed during July 1988 to December 1989. Primary cesarean section
      incidence varied according to indications, maternal parity and maternity care
      units. Foetal distress (65.9%), malpresentation and cephalopelvic disproportion
      (22.1%) were the dominant organic risk factors for the primary cesarean section.
      Multivariate stepwise logistic regression technique indicated that the most
      important indications for the practice in Cotonou were mainly organic risk
      factors, maternal height and parity as well as repeating stillborn history.
      Practician experiences (OR = 6.6) and foetal distress (OR = 9.3) in the decision
      making process were highly associated to cesarean section and differed between
      maternity units. Authors provided some suggestion for improving the practice of
      cesarean section in Cotonou and in Benin.

PMID- 8134666
TI  - Aids-related knowledge and practices in migrant populations: the case of
      Montrealers of Haitian origin.
AB  - The objectives of the study were to determine knowledge levels regarding AIDS and
      its modes of transmission, and to describe sexual behaviour of Montrealers of
      Haitian origin. A serial cross-sectional study was conducted in three phases
      between 1987 and 1990. A questionnaire was administered in a face-to-face
      interview with the exception of the section concerning sexual practices which was
      self-administered for those respondents who were literate in French. The study
      was conducted among 775 men and women residing in the metropolitan Montreal
      region. These individuals were aged 15 to 39, were born in Haiti or had at least
      one parent born in Haiti. Knowledge levels were high except for misconceptions
      about HIV transmission through casual contact and mosquito bites. There was a
      significant association between high risk sexual behaviour and marital status
      with the odds of having had multiple partners significantly raised for previously
      married individuals (OR = 5.96, 95% CI = 3.09; 11.50). High risk behaviour was
      also associated with being under 25 years of age (OR = 2.83, 95% CI = 1.40;
      5.74), knowing someone with HIV/AIDS (OR = 1.88, 95% CI = 1.05; 3.37), being male
      (OR = 6.81, 95% CI = 3.99; 11.60) and earlier year of interview. Montrealers of
      Haitian origin, with their specific AIDS-related socio-cultural characteristics,
      constitute a community which is intermediate between their country of origin,
      Haiti, and their host country, Canada.

PMID- 8134667
TI  - [Measurement errors and linear regression].
AB  - The consequences of a measurement error of known variance in the explanatory
      variable of a linear regression were assessed. On the average, the ordinary least
      squares (OLS) method underestimated the regression slope, the bias increasing
      with the variance of the measurement error and the strength of the relationship.
      Simulation results showed that the corrected-for-the-error estimate slightly
      overestimated the slope, the bias increasing with the variance of the measurement
      error and the strength of the relationship, but rapidly decreasing when the
      number of observations increased. In all cases the corrected estimate has a
      larger variance than the OLS estimate, Nevertheless, the mean square deviation of
      the corrected estimate to the "true" slope value can be smaller than the OLS one,
      even for a relatively small number of observations (< or = 100). In those
      conditions, the corrected estimate might be preferred when a "good estimation" of
      the regression slope is needed. Whereas a measurement error in the dependent
      variable, does not bias the slope estimator, when it is independent of the error
      in the explanatory variable, this is not the case when both measurement errors
      are correlated. An example of the need to correct for such a correlation is
      given.

PMID- 8134668
TI  - [Illness-based payment to hospitals: the French experience].
AB  - Since 1991, the French government is experiencing case based prospective payment
      mechanisms for public and for profit private hospitals. The experiments are the
      final objective of a program launched in 1982 to implement Diagnosis Related
      Groups (DRG) in France. Experiments are described and discussed. The relevance of
      the DRG classification is questioned, as well as the potential incentives
      embedded in the payment scheme. In the public sector, a case based prospective
      budgeting method is tested, to re-allocate resources according to case mix and
      relative costs. In the for profit sector, a prospective payment per case is
      designed, with price and volume adjustment inside a global cap of expenses. The
      experiments are a first step towards the unification of payment methods in both
      sectors. But important differences still remain, dealing with the scope of the
      payment method and the rate-setting basis. All expenditures will be covered in
      the public sector, physician fees are excluded in the private sector. The rates
      are based on actual cost in the public sector, on actual bills for the private
      sector.

PMID- 8134669
TI  - [Poisson regression in epidemiology].
AB  - The goals of Poisson regression are to estimate the effects of risk factors on
      incidence or mortality rates and to evaluate the dose-response relationship for
      variables representing quantitative levels of exposure. This statistical model
      presents, over standardization techniques, several advantages which are recalled
      here. The Poisson assumption, approximating the exact sampling distribution of
      rates is discussed. The model equation with internal and external standard rates
      is introduced, as well as summary measures of fit. Two examples are given: one
      from a cohort study, the other one from a geographical study, to help in the
      interpretation of Poisson regression results. Lastly, recent and on-going
      developments of these models are briefly considered.

PMID- 8134670
TI  - [Impact of AIDS on general mortality in France].

PMID- 8134671
TI  - [Anthropometric values of nutritional status in a population of elderly persons
      in France].

PMID- 8134672
TI  - [Epidemiology of diabetes: meeting of the international Group in Noumea].

PMID- 8134673
TI  - [Effects of premedication in children with congenital cardiopathy].
AB  - OBJECTIVES: To evaluate the effects of premedication in children with congenital
      heart disease. MATERIAL AND METHODS: Twenty-five children scheduled for surgical
      repair of congenital heart defects were studied. Two groups were formed based on
      whether cardiopathy was noncyanotic (group CNC) or cyanotic (group CC). Patients
      were premedicated rectally with 4 mg/kg pentobarbital and, 15 minutes later, with
      0.15 mg/kg of morphine chloride by subcutaneous perfusion. SpO2 was monitored, as
      was the degree of sedation and airway obstruction prior to premedication (T1), 15
      minutes after administration of pentobarbital (T2) and 30 minutes after morphine
      (T3). RESULTS: In the children with cyanotic cardiopathy, SpO2 increased over T1
      (75.5 +/- 8.7%) at times T2 (76.2 +/- 7.7%) and T3 (78.1 +/- 8%), although the
      change was not statistically significant. In group CNC, average SpO2 did not
      change, although one case of clinically significant desaturation due to
      hypoventilation was observed at T3. Adequate sedation was attained in 36% of
      patients at T2 and in 80% at T3 (p < 0.002). There were no cases of airway
      obstruction. CONCLUSION: Premedication with 4 mg/kg pentobarbital rectally does
      not provide adequate sedation. Addition of 0.15 mg/kg subcutaneous morphine
      chloride increased the effect considerably, providing stability in SpO2 and even
      improving it in group CC.

PMID- 8134674
TI  - [Evaluation of the hemodynamic and endocrino-metabolic response to tracheal
      intubation in patients anesthetized with thiopental or propofol].
AB  - OBJECTIVES: To compare the effects of thiopental and propofol on hemodynamic and
      metabolic endocrine response to laryngoscopy and intubation. MATERIAL AND
      METHODS: We selected two homogeneous groups of 14 healthy patients premedicated
      with midazolam i.m. (0.07 mg/kg). Induction was with diazepam (0.1 mg/kg),
      fentanyl (2 micrograms/kg), atropine 0.5 mg and thiopental or propofol (4-6.5
      mg/kg and 1.5-2.5 mg/kg, respectively). Parameters recorded were direct arterial
      pressure, baseline heart rate, and heart rate after induction and at 2 and 5
      minutes after intubation. We measured adrenaline (A), noradrenaline (NA),
      dopamine (Da), glucagon, beta-endorphines, ACTH, cortisol, glucose and amino
      acids in the baseline and post-intubation blood samples. RESULTS: We observed a
      significant increase (p < 0.05) in systolic and diastolic arterial pressure after
      intubation (10% and 22% respectively) in the thiopental group as compared with
      the propofol group. With both induction agents, heart rate was higher than
      baseline values at the three times (p < 0.001). In the thiopental group heart
      rate was higher after intubation than after induction (p < 0.05). Cortisol fell
      after intubation in the propofol group (p < 0.05); no other hormonal differences
      were observed. Hyperglycemia (p < 0.0001) was similar for both groups, while in
      the propofol group there were significant decreases in several amino acids.
      CONCLUSIONS: Propofol has a greater mitigating effect on the hyperdynamic
      response to intubation in healthy patients. For the two induction agents we
      measured no significant differences in stress hormone levels, apart from the drop
      in cortisol with propofol. We observed a change in energy-producing metabolites.

PMID- 8134675
TI  - [Comparison of oxygen saturations in mixed venous and central blood during
      thoracic anesthesia with selective single-lung ventilation].
AB  - OBJECTIVES: To establish the ratio of oxygen saturation in mixed venous to that
      of central venous blood in patients undergoing thoracic surgery, in order to
      rationalize use of the pulmonary arterial catheter. MATERIAL AND METHODS: We
      compared simultaneous spectrophotometric in vivo measurements for SvO2 [Abbott
      Oximetrix 3/SvO2 (O)] and in vitro analysis of blood taken from the distal
      opening of the catheter (co-oximeter/SvO2 [CO]), with in vitro analysis of
      central venous blood from the superior vena cava (co-oximetry/SvcO2 [CO]) for 23
      patients scheduled for lung resection by thoracotomy in lateral decubitus with
      single lung ventilation and the same type of monitoring and anesthesia.
      Measurements were taken 15 min after induction (M1), after 15 minutes in lateral
      decubitus (M2), 5 minutes after pleurotomy (M3), 5 min (M4) and 20 min (M5) after
      lung collapse, 5 min after closure of the thoracic wall (M6) and after 5 min
      supine (M7). RESULTS: SvO2(O) was higher than SvcO2 (CO) at M1, M3, M6 and M7 and
      the mean difference between the two concentrations was always less than 0.9%.
      SvcO2 (CO) was always higher than SvO2 (CO) (M1 to M7) and the mean difference
      was less than 1.3%. Simple linear correlation was significant (p < 0.001) for
      each of the measurements as well as for the whole sample. Both bias (0.2 and
      0.7%) and its standard deviation (2.7 and 2.5%) between the two techniques were
      small and the differences between all measurements were less than 5% in 97 and
      95.6%. CONCLUSION: For thoracic anesthesia in patients who are not good
      candidates for catheterization of the pulmonary artery, continuous measurement of
      SvO2 may be substituted for that of SvcO2 in order to monitor the balance of
      supply/demand.

PMID- 8134676
TI  - [Comparative study of propofol and midazolam for sedation in regional
      anesthesia].
AB  - OBJECTIVES: To compare the efficacy of propofol and midazolam as sedatives in non
      premedicated patients receiving regional anesthesia. MATERIAL AND METHODS:
      Parameters measured were quality of sedation, intraoperative changes in
      hemodynamics, respiration and plasma biochemistry as compared with baseline,
      preinduction and post-anesthetic recovery levels. Forty patients were distributed
      randomly into two groups. Group P (n = 20) received an infusion of 1% propofol
      (10 mg/ml) at an initial rate of 6 mg/kg/h for 10 minutes, later decreased to 3
      mg/kg/h. Group M (n = 20) received an infusion of 0.3% midazolam with an initial
      bolus of 0.06 mg/kg along with simultaneous infusion at a rate of 0.05 mg/kg/h.
      RESULTS: Adequate sedation that was easily controlled during surgery was attained
      in both groups. The mean doses used were 336.7 +/- 33.7 mg in group P and 10.1 +/
      1.1 mg in group M. No significant changes in hemodynamic and respiratory
      parameters were observed. Differences between baseline and preinduction levels
      were found in some analyses, but significant changes during surgery were recorded
      only for HCO3-. There were no differences in recovery time from the moment
      infusion ceased until spontaneous eye opening and recall of date of birth. The
      degree of amnesia was greater in the midazolam group. The lesser amnesia with
      propofol meant that psychological measures were higher (p < 0.01). No differences
      in side effects were found. CONCLUSION: Continuous perfusion of propofol and
      midazolam for sedation in regional anesthesia are equivalent with respect to
      efficacy and safety.

PMID- 8134677
TI  - [Internal jugular vein catheterization performed by resident and staff
      physicians].
AB  - OBJECTIVES: To analyse complications in the catheterization of the internal
      jugular vein using the Boulanger technique and to establish a rating of
      difficulty and risk when the procedure is carried out by physicians in training.
      MATERIAL AND METHODS: This was a prospective study of 296 internal jugular vein
      (IJV) catheterizations by the Boulanger technique carried out by physicians in
      training (group R2 and group R3-4) or by departmental staff physicians (group
      staff). Time taken for venous catheterization, rate of success and complications
      were recorded for each physician performing the procedure. RESULTS: The
      complication most often observed (11.4%) was puncture of the carotid artery
      (14.3% group R2, 10% group R3-4 and 8.2% staff), followed by arrhythmia upon
      insertion of the metal guide (1.6%). There were no instances of pneumothorax or
      hemothorax, nor any other of the early complications considered infrequent.
      Success ranged from 68.8% for group R2 to 85.7% for staff. Mean time used in
      group R2 was 238.7 seconds, while for staff it was 118.3 seconds. CONCLUSION: We
      suggest that the Boulanger technique for catheterization of the internal jugular
      vein is a good one and is not particularly hazardous when performed by resident
      physicians in training.

PMID- 8134678
TI  - [Use of a double-lumen tube with intermittent positive ventilation in a case of
      distal tracheal laceration].
AB  - We discuss the management of anesthesia in a patient brought to hospital
      following a traffic accident in which she suffered distal laceration of the
      trachea and unstable vertebral fracture that met surgical criteria. Our main
      objectives were to avoid placing positive pressure on the damaged trachea and to
      extubate immediately after surgery. Using a left double-lumen endotracheal tube
      guided by flexible bronchoscope, we administered general anesthesia with
      mechanical ventilation and positive pressure, with no air leakage through the
      damaged area. Anesthesia was maintained by continuous perfusion of propofol,
      allowing good hemodynamic stability and rapid extubation. We conclude that this
      will be a useful procedure in similar cases when no other form of mechanical
      ventilation is available.

PMID- 8134679
TI  - [Anesthesia for vertebral osteoclasis in a patient with severe predominantly
      cervical spondylitis ankylopoietica].
AB  - We present a patient suffering severe, mainly cervical, ankylopoietic spondylitis
      who was scheduled for posterior vertebral osteoclasis under local anesthesia. We
      describe handling of anesthesia, particularly airway control by flexible
      bronchoscopy in an awake, locally anesthetized patient sedated with
      benzodiazepines and inhalational anesthetics as compared with other alternatives:
      an awake patient who is not intubated, under local anesthesia and sedated with
      narcotics and gaseous anesthetics, or a patient under general anesthesia with
      placement of a flexible bronchoscope and neurological monitoring by evoked
      potentials. The surgical technique was Simmons' posterior vertebral osteoclasis,
      with the column extended and immobilized with wire.

PMID- 8134680
TI  - [Anesthetic factors which affect ocular tone].

PMID- 8134681
TI  - [Continuous perfusion with midazolam and atracurium in a patient with severe
      tetanus].

PMID- 8134682
TI  - [Anesthesia in Sotos' syndrome].

PMID- 8134683
TI  - [Headache after dural puncture in young patients. Prospective study of 611 cases
      using a 24-gauge "pencil-point" needle].

PMID- 8134684
TI  - [Cryoanalgesia in post-thoracotomy pain].

PMID- 8134685
TI  - [Ondansetron in ambulatory surgery].

PMID- 8134686
TI  - [Late reperfusion in myocardial infarct patients: the evidence of a beneficial
      effect].

PMID- 8134687
TI  - [Protocols for the prevention and treatment of thromboembolic disease. (III). The
      prevention of an embolism of cardiac origin. The Editorial Committee on
      Protocols].

PMID- 8134688
TI  - [Protocols for the prevention and treatment of thromboembolic disease. (IV).
      Antithrombotic therapy in coronary disease. The Editorial Committee on
      Protocols].

PMID- 8134689
TI  - [Protocols for the prevention and treatment of thromboembolic disease. Appendix.
      Summary of the levels of evidence and the degrees of recommendation set forth in
      the text. The Editorial Committee on Protocols].

PMID- 8134690
TI  - [The National Heart Transplant Registry. 4th report (1984-1992)].

PMID- 8134691
TI  - [The female sex and mortality after acute myocardial infarct].
AB  - INTRODUCTION: To study the possible influence of gender on in-hospital mortality
      in patients suffering acute myocardial infarction. PATIENTS AND METHODS: We
      analyzed 1,951 consecutive patients admitted to our Coronary Unit between January
      1986 and December 1991 with this diagnosis and with a delay of no more than 24
      hours prior to admission. RESULTS: In-hospital mortality was 12.8% in the 1,603
      males and 25.6% in the 348 females (p < 0.001). Age, previous history of: not
      smoking, diabetes, heart failure, stable angina, myocardial infarction, stroke,
      right branch block, atrial fibrillation, and treatment with digoxin were
      variables significantly associated with greater mortality (p < 0.05) as well as
      the localization of the infarction, the Forrester grade and/or presence of
      atrioventricular block on admission and not treatment with intravenous
      fibrinolytics and beta-blockers. Multivariate analysis of variables associated
      with mortality (selection criterion for variable entry p < 0.20) shows that age,
      gender, previous angina, situation and extension of the infarction determined by
      ECG and Forrester on admission are independent predictors of in-hospital
      mortality. CONCLUSIONS: Gender is an independent predictor of in-hospital
      mortality in acute myocardial infarction (female/male odds ratio = 1.63).

PMID- 8134692
TI  - [Ischemic cardiopathy in women: the current status of the problem].

PMID- 8134693
TI  - [Transesophageal echocardiography in the diagnosis of aortic dissection].
AB  - INTRODUCTION AND OBJECTIVE: Eighty-two patients with suspected aortic dissection
      were studied to assess the usefulness of transesophageal echocardiography in the
      diagnosis of this entity. METHODS: All patients underwent transesophageal
      echocardiogram. The diagnosis of aortic dissection was established in 46 patients
      by other diagnostic procedures including angiography and computed tomography,
      surgery and necropsy. RESULTS: The sensitivity and specificity of transesophageal
      echocardiography were 98% and 97%, respectively. By computed tomography,
      sensitivity was 92% and specificity 88%. By angiography, sensitivity and
      specificity were 97% and 93%, respectively. In the diagnosis of the dissection
      type, transesophageal echocardiography classified correctly in 98%, computed
      tomography in 89% and angiography 97% of cases. Transesophageal echocardiography
      visualized the tear in 82% of cases, and angiography in 53%. CONCLUSIONS:
      Transesophageal echocardiography provides rapid, accurate diagnosis of aortic
      dissection and permits the initiation of appropriate treatment. Angiography is
      indicated in non-conclusive cases or those which supra-aortic involvement
      clinically suspected.

PMID- 8134694
TI  - [Transthoracic and transesophageal echocardiography in the pre- and postoperative
      assessment of interatrial communication].
AB  - BACKGROUND AND OBJECTIVES: Transthoracic echocardiography is the most useful
      noninvasive method to diagnose atrial septal defect. It is suggested by some
      authors that transesophageal echocardiography is more accurate than transthoracic
      echocardiography in this setting. Our aim was to compare the usefulness of both
      techniques in: 1) diagnosing atrial septal defect, 2) detecting associated
      anomalies and 3) postoperative assessment. PATIENTS AND METHODS: Pre and
      postoperative transthoracic and transesophageal echocardiography were performed
      in 27 patients in whom diagnosis of atrial septal defect was confirmed at
      surgery. RESULTS: Transthoracic echocardiography demonstrated the defect in 20
      patients (74%) (8 ostium primum, 10 ostium secundum and 2 sinus venosus). The 27
      patients (100%) were correctly diagnosed by transesophageal echocardiography (8
      ostium primum, 12 ostium secundum and 7 sinus venosus). Defect size determined by
      transthoracic echocardiography had a poor correlation with the surgical
      measurement (r = 0.34). A good correlation was obtained when transesophageal
      versus surgical defect size measurements were compared (r = 0.85; p < 0.05).
      Transesophageal echocardiography was superior in detecting associated anomalies
      (5 patients with anomalous partial pulmonary venous drainage, 3 persistence of
      left superior vena cava and 1 atrial septal aneurysm). Moreover, this technique
      better determined residual atrial septal defect, and detected a postsurgical
      inferior vena cava connection to the left atrium. CONCLUSIONS: Transesophageal
      echocardiography is superior to transthoracic echocardiography in diagnosing
      atrial septal defect sinus venosus type, detecting associated anomalies and
      postoperative assessment. Transthoracic echocardiography is diagnostic in the
      majority of patients with atrial septal defect ostium primum and ostium secundum
      types.

PMID- 8134695
TI  - [Atrial septostomy with a balloon catheter under echocardiographic control. Our
      experience].
AB  - INTRODUCTION: We report our experience in balloon atrial septostomy using two
      dimensional echocardiography as control for the catheter placement and
      performance of the procedure instead of traditional fluoroscopic control.
      PATIENTS AND METHODS: We carried out atrial septostomy in 12 consecutive neonates
      with age between 1 and 18 days (mean = 3.6 +/- 5 days) diagnosed as d
      transposition of the great arteries (10 cases) and pulmonary atresia with intact
      ventricular septum (2 cases). The procedures were performed in the
      catheterization laboratory in 7 cases. In the five remaining cases it was done in
      the neonatal intensive care unit. We emphasise the good visualization of the full
      balloon within the left atrium and its relationship with the mitral valve and the
      pulmonary veins, as well as, the problems found in case number 2 for initial
      placement of the catheter in the left atrium. RESULTS: An adequate atrial septal
      defect was achieved in all patients with diameter between 6 and 12 mm (mean = 8.6
      +/- 2 mm). There were no complications using this technique, except a
      supraventricular tachycardia which stopped spontaneously. The evolution of the
      patients have been satisfactory, and 11 of them underwent surgery. Patient number
      2 died suddenly on the third day after atrial septostomy. CONCLUSIONS: We
      conclude that atrial septostomy with balloon catheter can be carried out safely,
      under echocardiographic control in the intensive care unit. Above all, critical
      patients should not be removed from the unit because they are high risk patients.

PMID- 8134696
TI  - [Cardiac arrhythmias (XII). The implantable automatic defibrillator as the
      treatment of malignant ventricular arrhythmias].

PMID- 8134697
TI  - [A suicide attempt with oral verapamil: a case report].
AB  - We report a case of a 29-years-old patient who tried to commit suicide by taking
      a high dose of verapamil (22 pills containing 240 mg, each, equivalent to 5.28
      g). Ten hours after the ingestion he presented a complete atrioventricular heart
      block which was resolved with medical treatment presenting a normal ECG 36 hours
      later. To our knowledge this is the only published case of intoxication caused by
      such a high dose of verapamil.

PMID- 8134698
TI  - [Hypertrophic obstructive myocardiopathy complicated by severe mitral
      insufficiency secondary to rupture of the chordae tendineae].
AB  - A case of suddenly increasing dyspnea in a patient with hypertrophic obstructive
      cardiomyopathy is reported. Transesophageal echocardiography showed severe mitral
      regurgitation secondary to ruptured chordae tendineae. Mitral valve replacement
      was done, correcting both mitral regurgitation and subaortic gradient. Utility of
      transesophageal echocardiography in diagnosis and therapeutic options are
      discussed.

PMID- 8134699
TI  - [Fistula from the coronary artery to the peripheral branches of the left
      pulmonary artery].
AB  - A case is presented of a coronary artery fistula originating in the circumflex
      artery which drains in a branchified pattern in the peripheral branches of the
      left pulmonary artery. The diagnosis came as a result of a diagnostic
      coronarography in a woman with ischemic cardiopathy. The etiology, evolution and
      treatment of this exceptional coronary anomaly is being discussed.

PMID- 8134701
TI  - Ischemia-mediated neuronal injury.
AB  - Resuscitation of the brain after a period of global ischemia is limited by two
      classes of post-ischemic pathologies: hemodynamic disturbances which prevent the
      adequate re-oxygenation of the ischemic brain, and metabolic disturbances which
      may lead to delayed neuronal death in so-called selectively vulnerable brain
      regions. The hemodynamic disturbances can be classified into the no-reflow
      phenomenon and the post-ischemic hypoperfusion syndrome. The no-reflow phenomenon
      results from a combination of increased blood viscosity and perivascular edema;
      the severity increases with the duration of ischemia, and the treatment is by
      combining arterial hypertension with dehydration and anticoagulation. The post
      ischemic hypoperfusion syndrome is independent of the duration of ischemia, it
      develops after a delay and is due to an impairment of the metabolic/hemodynamic
      coupling mechanisms; there is no specific treatment at the present. The most
      important metabolic disturbance leading to delayed neuronal death is prolonged
      inhibition of protein synthesis. The injury is manifested already after 5 min
      ischemia but it progresses little if ischemia is prolonged to 1 h. Inhibition
      occurs at the translation level due to selective inhibition of polypeptide chain
      initiation. After brief periods of ischemia, the disturbance can be reversed by
      various anesthetics and hypothermia but there is no treatment if ischemia is
      prolonged. Exitotoxity, free radical-mediated reactions, disturbances of
      polyamine metabolism, acidosis and selective disturbances of gene expression may
      also be involved but are probably of lesser importance.

PMID- 8134700
TI  - [Prolonged asystole requiring resuscitation measures during a head-tilt table
      test].

PMID- 8134702
TI  - Pentoxifylline alone versus pentoxifylline combined with superoxide dismutase
      prolongs survival in a rat hemorrhagic shock model.
AB  - Pentoxifylline (PTX) and superoxide dismutase (SOD) have each proven effective in
      improving survival when administered during resuscitation in animal models of
      hemorrhagic shock. This study was conducted to determine if PTX and SOD combined
      would have synergistic effectiveness in the treatment of hemorrhagic shock.
      Sprague-Dawley rats (n = 40) were phlebotomized at 25 ml/kg for 2 min, then
      subjected to a 45-min ischemic period, and resuscitated with lactated Ringer's
      solution (LR) (50 ml/kg) over 1 h. This model resulted in 70% mortality over 72 h
      when resuscitation was with LR alone. Animals were randomized into groups to
      receive one of the following agents during resuscitation: PTX in LR, SOD in LR, a
      combination of PTX and SOD in LR, or LR alone. PTX or SOD alone were effective in
      prolonging survival. However, the combination of PTX and SOD did not prolong
      survival above LR control.

PMID- 8134703
TI  - Early volume expansion during cardiopulmonary resuscitation.
AB  - OBJECTIVE: To determine if hemodynamic parameters, return of spontaneous
      circulation (ROSC), and short term survival are improved by volume expansion
      during resuscitation from ventricular fibrillation cardiac arrest. DESIGN:
      Randomized protocol. SETTING: Animal research laboratory. PARTICIPANTS: 18
      conventional swine. INTERVENTIONS: Ventricular fibrillation was electrically
      induced after instrumentation. All swine fibrillated without intervention for 5
      min and received 13 min of mechanical high-impulse (HICPR) prior to
      randomization. The resuscitation protocol included either epinephrine (0.014
      mg/kg) alone (Group A) or epinephrine with a fluid bolus (4 cc/kg) of hypertonic
      saline-dextran (HSD) solution (Group B). MEASUREMENTS AND MAIN RESULTS: Group A
      had 6/9 and Group B had 5/9 swine achieve ROSC and 2/9 vs. 4/9 swine survived 30
      min, respectively (P = NS). Coronary perfusion pressures (CPP) measured during
      HICPR at 60, 90, and 120 s after infusion were not significantly different for
      the two groups. At 1 min after ROSC, CPP, aortic systolic blood pressure (AoSBP),
      and aortic diastolic pressure (AoDBP) were all significantly greater in Group B
      than in Group A (P < 0.05). Arterial and venous blood gases measured at 1 min
      after ROSC revealed a significantly lower pH and higher PCO2 in Group B animals.
      CONCLUSION: Early volume expansion with epinephrine during HICPR does not improve
      CPP, rate of ROSC, or rate of short term survival from VF arrest in this porcine
      model. HSD volume expansion does improve systemic hemodynamics after ROSC with
      increased CPP, AoSBP, and AoDBP. Improved tissue perfusion in Group B animals
      after ROSC is suggested by a decreased pH and increased PCO2 presumably secondary
      to enhanced mobilization of lactate and PCO2 from tissues.

PMID- 8134704
TI  - Cardiopulmonary resuscitation without intermittent positive pressure ventilation.
AB  - The purpose of this study was to examine whether tracheal insufflation of oxygen
      (TRIO) could be used as a substitute for intermittent positive pressure
      ventilation (IPPV) during cardiopulmonary resuscitation (CPR) in dogs with
      orotracheal intubation. Twenty-seven anesthetized, paralyzed and intubated dogs
      were used. The tip of the insufflation catheter was placed 1 cm distal to the top
      of the endotracheal tube. The effects of TRIO at a flow rate of 10 l/min with or
      without a continuous positive airway pressure (CPAP) of 5 cmH2O during external
      cardiac compressions were compared with those managed under the standard CPR.
      During CPR, TRIO without CPAP maintained adequate gas exchange. Peak airway
      pressures in the TRIO groups were significantly lower than that in the standard
      CPR group. No significant differences were observed in arterial, pulmonary artery
      and diastolic right atrial pressures during CPR among the three groups. However,
      the coronary perfusion pressures in the TRIO group with CPAP always tended to be
      low during CPR. The present study suggests that TRIO without CPAP should be a
      promising substitute for IPPV during CPR when IPPV is not feasible.

PMID- 8134705
TI  - The effect of global ischemia and reperfusion on the plasma levels of vasoactive
      peptides. The neuroendocrine response to cardiac arrest and resuscitation.
AB  - OBJECTIVE: Return of spontaneous circulation with CPR is a function of coronary
      perfusion pressure, which is determined by vasomotor tone and the force of
      compression. Vasomotor tone is affected by the relative stimulation of arterial
      vasoconstricting and vasorelaxing receptors by vasoactive substances. We measured
      the plasma levels of the endogenous vasoactive peptides arginine vasopressin
      (AVP) angiotensin II (ANG-II) and atrial natriuretic peptide (ANP) during cardiac
      arrest and resuscitation. DESIGN: A fibrillatory canine model of canine arrest
      was used. 'Down time' was greater than 10 min, during which no therapy, including
      BLS, was given. Standard ACLS was initiated at the end of the down time with
      manual external chest compression standardized to an esophageal pulse pressure of
      50 mmHg. Blood samples were collected through an aortic catheter during
      spontaneous circulation and 3 min after initiation of ACLS. Peptide levels were
      measured using standard RIA techniques. Results are reported as the mean +/- S.D.
      in pg/ml. RESULTS: AVP levels increased from a baseline of 1.7 +/- 1.0 pg/ml
      during spontaneous circulation to 29.9 +/- 33.3 during cardiac arrest and CPR (P
      = 0.01). There was a moderate positive correlation between aortic pressure and
      circulating AVP levels after the first dose of epinephrine (R = 0.5). There was a
      trend towards higher AVP levels in animals with return of spontaneous circulation
      (P = 0.12). ANG-II levels increased from a baseline of 14.7 +/- 12.9 pg/ml during
      spontaneous circulation to 151 +/- 105 during cardiac arrest and CPR (P < 0.05).
      ANP levels increased from a baseline of 55 +/- 46 pg/ml during spontaneous
      circulation to 293 +/- 73 during cardiac arrest and CPR (P < 0.01). CONCLUSION:
      There were significant increases in the levels of these endogenous vasoactive
      peptides. This reflects the neuroendocrine response to global ischemia and CPR
      reperfusion. Plasma levels of these peptides may effect the vital organ perfusion
      pressures, response to exogenous vasopressors, and outcome of resuscitative
      efforts. Future therapies may be directed at enhancing or blocking the effect of
      these peptides so as to optimize perfusion pressure which is one of the principle
      determinants of outcome during CPR.

PMID- 8134706
TI  - Emergency intubation with the Combitube in a grossly obese patient with bull
      neck.
AB  - A grossly obese patient with bull neck required immediate intubation.
      Endotracheal intubation failed because visualization of the vocal cords was not
      possible. As an alternative, the Combitube was inserted without difficulty and
      the patients lungs were ventilated via the Combitube until tracheotomy was
      performed on the following day. The patient survived and was discharged alive
      from the hospital 5 weeks later. The Combitube has gained worldwide interest and
      is now included in the Guidelines of the American Heart Association and the
      American Society of Anesthesiologists.

PMID- 8134707
TI  - Brain-oriented intensive care and the no-reflow phenomenon.

PMID- 8134708
TI  - Complications of sarcoidosis. Chronic fatigue syndrome.
AB  - Well-recognised complications are pulmonary fibrosis, cor pulmonale, glaucoma,
      cataract and nephrocalcinosis causing failure of lungs, heart, vision and
      kidneys. Less well-recognised is the post-sarcoidosis chronic fatigue syndrome.
      The afflicted join sarcoidosis patients' associations because of their profound
      symptoms of myalgia, fatigue, sleep reversal and low-spiritedness. The symptoms
      are out of proportion to the lack of physical signs and the absence of objective
      evidence of sarcoidosis. Management includes unremitting sympathy and
      replenishment of essential neurochemicals.

PMID- 8134709
TI  - Elevated levels of tryptase in bronchoalveolar lavage fluid from patients with
      sarcoidosis.
AB  - Sarcoidosis affecting the lungs may cause obstructive and/or restrictive lung
      function impairment. The bronchial reactivity is related to the release of
      histamine from the mast cells. Upon activation mast cells also release tryptase.
      This enzyme may activate latent collagenase and thus possibly contribute to the
      fibrosis formation observed in sarcoidosis. We analyzed the bronchoalveolar
      lavage fluid (BALF) from 13 nonsmoking and untreated patients with sarcoidosis
      and from 30 healthy volunteers (18 smokers) with regard to the number of mast
      cells and the tryptase concentration. Concomitantly albumin, fibronectin and
      hyaluronan were measured as markers of the inflammatory reaction in the alveoli
      and interstitium. The number of mast cells was higher (p < 0.001) in patients
      with sarcoidosis than in controls. Also, the concentration of tryptase was
      significantly higher in patients (225.3 +/- 83.9 [SEM] mU/L) compared to
      nonsmoking and smoking controls (34.7 +/- 7.8 and 44.7 +/- 13.0 mU/L,
      respectively; p < 0.01 for both). In addition, the concentrations of albumin,
      fibronectin and hyaluronan were higher in patients with sarcoidosis compared to
      the nonsmoking controls (p < 0.001 for all). However, there was no relationship
      between either the mast cell number or the tryptase concentration and the lung
      function parameters (VC, TLC, FEV1, FEV%, DLCO). As our patients did not show any
      functional signs of bronchial obstruction (FEV1 91.7% +/- 13.3 [SD] and FEV%
      99.5% +/- 6.4 of predicted) the lack of correlation is not surprising. The high
      concentrations observed in the BALF of the noncellular components may just
      reflect an ongoing inflammatory process that may resolve or, if exaggerated, lead
      to fibrosis.

PMID- 8134710
TI  - Smoking does not prevent the onset of respiratory failure in sarcoidosis.
AB  - It has been suggested that smoking prevents the development of pulmonary
      sarcoidosis. If this is the case, it might also be expected to prevent or
      postpone the onset of respiratory failure caused by sarcoidosis. During the
      period January 1st 1987 to October 1st 1991, 28 patients (16 never-smokers, 11 ex
      smokers and one current smoker) were registered in the Swedish Oxygen Register
      when starting long-term domiciliary oxygen therapy (LTO) for chronic hypoxia
      caused by sarcoidosis. The register covers 85-90% of all patients starting LTO
      for respiratory failure in a population of 8.5 million. Ex-smokers were
      significantly younger at the start of LTO than never-smokers (p < 0.05),
      regardless of whether chronic airways disease was present or not. We found no
      indication that smoking exerts a preventive effect on the development of chronic
      hypoxia in sarcoidosis.

PMID- 8134711
TI  - Detection of antibodies in serum against M. tuberculosis using western blot
      technique. Comparison between sarcoidosis patients and healthy subjects.
AB  - Antibodies in serum of IgG and IgA class against Mycobacterium tuberculosis were
      detected by Western blot technique in 32 patients with pulmonary sarcoidosis and
      in 10 BCG and 10 non-BCG vaccinated healthy individuals. All three groups
      demonstrated multiple IgG and IgA antibodies against Mycobacterium tuberculosis
      protein antigens. Preabsorption of the sera with an Escherichia coli antigen did
      not influence the results. There were no consistent differences in the antibody
      profiles in patients with sarcoidosis and healthy subjects.

PMID- 8134712
TI  - Serologic reactivity against Mycobacterium paratuberculosis antigens in patients
      with sarcoidosis.
AB  - Although sarcoidosis has clinical and histopathologic similarities to some forms
      of tuberculosis and other mycobacterial infections, attempts to establish a
      mycobacterial etiology have not been successful. Using cytoplasmic antigens
      derived from a wild strain of Mycobacterium paratuberculosis in an enzyme-linked
      immunosorbent assay, patients with sarcoidosis were found to have immunoglobulin
      levels significantly higher than those found in a control population in the IgG,
      but not in IgA or IgM antibody classes. Results were comparable to those reported
      from patients with Crohn's disease, where M. paratuberculosis has been
      intensively studied as a possible etiologic agent. To elucidate these
      relationships, examination of DNA from sarcoid tissues for possible homology with
      DNA from M. paratuberculosis and closely related organisms, as well as cultural
      attempts with techniques and media appropriate for M. paratuberculosis may be
      warranted.

PMID- 8134713
TI  - Standardized quantitative 67Ga scintigraphy in relation to carbon monoxide
      diffusion capacity in pulmonary sarcoidosis.
AB  - 67Ga lung uptake, obtained by a standardized computer-assisted quantitative
      method of 67Ga scintigraphy, was compared to carbon monoxide diffusion capacity
      (DLCO) in 45 patients with biopsy proven pulmonary sarcoidosis. Increased 67Ga
      lung uptake was found in 24 (53%) patients and DLCO was decreased in only 16
      (36%) patients. An inverse relationship (r = -0.53; p < 0.001) was demonstrated
      between 67Ga lung uptake and DLCO. Eleven patients had an increased 67Ga lung
      uptake whereas the DLCO values were normal. There was no correlation between 67Ga
      lung uptake or DLCO and either chest radiographic stage or mode of clinical
      presentation. On the basis of the normal limits for 67Ga lung uptake and DLCO, 4
      subgroups of patients could be identified. The use of the combined investigations
      may open an opportunity for an early identification of those patients who require
      therapy. An increased 67Ga accumulation within the lung seems to be considered as
      a factor indicating risk for pulmonary disability, which is supported by the
      follow-up of the 4 subgroups of patients.

PMID- 8134714
TI  - Acute myeloblastic leukemia and sarcoidosis.
AB  - A protracted unexplained blood dyscrasia, and late age of onset were peculiar
      features observed in several of the nine reported instances of sarcoidosis in
      which acute myeloblastic leukemia evolved. These characteristics, in combination
      with the observed frequency with which the two disorders have been linked, and
      numerous previous reports of malignancy-associated sarcoidosis, suggest that the
      conjunction in non-fortuitous. Seven criteria are proposed which might be
      employed to support a causal relationship between sarcoidosis and malignancy. A
      systemic granulomatous response to tumor antigen, analogous to regional sarcoid
      reactions, is offered as a possible explanation for this association.

PMID- 8134715
TI  - Diagnostic criteria for chronic beryllium disease (CBD) based on the UK registry
      1945-1991.

PMID- 8134716
TI  - Granulomatous response to Pneumocystis carinii in patients infected with HIV.
AB  - Pneumocystis carinii is the most frequent manifestation of the acquired immune
      deficiency syndrome. Typical histologic findings include foamy, acellular
      eosinophilic intra-alveolar exudate in which the cysts of the organisms are
      readily demonstrated with silver stains. Granuloma formation is rare. Only nine
      such cases have been described in the English literature. We reviewed 400
      transbronchial biopsies done in patients suspected of having pneumocystis
      pneumonia at our institution between the period of 1987-1990. Of the 320 biopsy
      specimens with Pneumocystis carinii identified, 17 cases had granulomatous
      inflammation with or without Pneumocystis carinii present. All cultures for
      tuberculosis and fungi were negative during initial admission and follow up in
      fifteen cases. One was later found to have tuberculosis and another about 6
      months later histoplasmosis, when rebronchoscoped for suspicion of recurrent
      Pneumocystis infection. None of our patients had clinical evidence for
      sarcoidosis or hypersensitivity pneumonitis. We believe that granulomatous
      pneumonitis should be included in the list of pulmonary complications associated
      with Pneumocystis carinii pneumonia. Clinical significance and immunologic nature
      remains unexplained.

PMID- 8134717
TI  - Sarcoidosis in native Saudis.
AB  - Sarcoidosis is believed to be rare in Saudi Arabia. We report twenty cases of
      sarcoidosis among native Saudis followed-up at our tertiary care centre. The
      majority (55%) of these patients were referred as either tuberculosis or
      lymphoma. Twelve out of twenty patients had been or were being treated for
      pulmonary tuberculosis at the time of presentation. The clinical presentation of
      these patients was similar to the western pattern of disease with some
      differences such as severe constitutional symptoms (52%), relative frequent eye
      involvement (35%) and common occurrence of stage II changes on chest film (70%).
      Mantoux skin test was negative in nineteen patients (95%). Histological evidence
      of non-caseating granulomata was obtained in 19 patients. A positive correlation
      (p < 0.034) between constitutional symptoms and Angiotensin Converting Enzyme
      (ACE) levels was noted. Thirteen patients (65%) were treated with oral steroids
      while topical ophthalmic steroids were used in seven patients (35%). Functional
      and radiographic deterioration was observed in four patients (20%). Three
      patients went into respiratory failure including a patient who developed
      Hodgkin's lymphoma six years after the diagnosis of sarcoidosis. The epidemiology
      of sarcoidosis among native Saudis requires further studies.

PMID- 8134718
TI  - Inhaled budesonide vs prednisone in the maintenance treatment of pulmonary
      sarcoidosis.
AB  - The aim of this investigation was to compare inhaled budesonide with oral
      prednisone in maintenance treatment of pulmonary sarcoidosis. A double-blind
      controlled study was performed in 40 patients with stage II or III pulmonary
      sarcoidosis. After initial systemic 6 weeks treatment with prednisone (40 reduced
      to 20 mg daily) patients were allocated either to the systematically (S) or
      topically (T) treated group. S patients continued with 10 mg prednisone daily, T
      patients were given inhaled budesonide 1.6 mg daily. The progress of treatment
      was assessed by serial radiography, spirometry, serum Angiotensin Converting
      Enzyme (ACE) activity and plasma cortisol levels. All patients completed the 12
      months treatment. Using the numerical score to assess changes on the chest
      radiograms S patients improved by 1.7 +/- 0.66 points; T patients improved by
      1.15 +/- 0.81 points. Spirometric changes were not statistically significant.
      Serum ACE fell from 107 +/- 51 U/L in the S group and 92 +/- 40 U/L in the T
      group to 46 +/- 11 U/L and 38 +/- 21 U/L respectively during the initial phase of
      treatment. In the maintenance phase ACE levels remained lower than the initial
      ones in both groups. Morning plasma cortisol levels studied in 10 patients (5 in
      each group) decreased significantly during the initial phase. Thereafter cortisol
      levels remained low in the S patients returning to the lower limit of normal
      values in the T patients. We conclude that inhaled budesonide may be a safe and
      effective alternative to oral steroids in the maintenance treatment of pulmonary
      sarcoidosis especially in the early stage of the disease.

PMID- 8134719
TI  - Ki-1 anaplastic large cell lymphoma: another masquerader of sarcoidosis. A case
      report.
AB  - Because of its heterogeneous presentation, Ki-1 lymphoma may be confused with
      other malignant and non-malignant conditions. We report a 34 year old male who
      came to us with skin lesions and generalized lymphadenopathy. Because the patient
      also had bilateral hilar lymphadenopathy, sarcoidosis was the initial diagnosis.
      The special stains and the morphological findings of fine needle aspiration of
      the skin lesions and bone marrow led to the diagnosis of Ki-1 anaplastic large
      cell lymphoma.

PMID- 8134720
TI  - Sarcoidosis of the thyroid: report of a case and a review of the literature.
AB  - A case of sarcoidosis involving the thyroid gland in a 75 year-old woman and a
      review of the literature are described. Fine-needle aspiration of the thyroid and
      a cervical lymph node was performed. Histological examination confirmed the
      cytological diagnosis.

PMID- 8134721
TI  - Arthur Conan Doyle and Jonathan Hutchinson: the sarcoidosis connection.

PMID- 8134722
TI  - Antibody responses to viral antigens in sarcoidosis.

PMID- 8134723
TI  - Mimics of sarcoidosis--endobronchial tuberculosis.

PMID- 8134724
TI  - [Brief analysis of the "Revista de Investigacion Clinica"].

PMID- 8134725
TI  - [Change in the quality of life as an indicator of the clinical course of disease.
      Comparison of 2 indices].
AB  - Quality of life is an important outcome measurement to judge disease impact and
      response to treatment; however it is very difficult to measure. We compared the
      MacKenzie's Change in Maximal Function Index (CMFI) with the Change in Quality of
      Life Index (CQLI) developed by our group. Both indices were applied on admission
      and upon discharge of 23 medical and surgical inpatients. The CQLI's
      interobserver reliability was somewhat better (Ri = 0.69) than that of the CMFI
      (Kw = 0.49). Both indices correlated with patient, close relative and physician
      assessments (rs = 0.52 to 0.86, p < 0.05). There was no correlation with
      Karnofsky scores. Both showed adequate responsiveness with Guyatt's coefficients
      between 2 and 4. Ninety five percent of the patients thought the questionnaires
      were easy to answer and approximately 5 minutes were enough to complete them.
      Both indices seem to perform better when applied by a social worker than when
      applied by a physician. Our results suggest that it is feasible to obtain
      consistent estimates of changes in quality of life. Either one of these indices
      may be used to assess the impact of medical intervention.

PMID- 8134726
TI  - [Experience with a screening program for gestational diabetes].
AB  - OBJECTIVE: To determine the prevalence of gestational diabetes (GD) in an
      outpatient clinic in northeastern Mexico. PATIENTS: 732 consecutive pregnant
      women referred for prenatal care during a two-year period. INTERVENTION AND
      OUTCOME MEASURE: A 100 g glucose tolerance test was performed in the patients
      with sampling at 1, 2 and 3 hours postchallenge. The patients were classified
      according to the criteria of the American Diabetes Association as normal,
      abnormal, and a third category of those showing a single abnormal value in the
      tolerance test. RESULTS: Six percent of the women (44/732) had GD and 1.4%
      (10/732) had one abnormal value. A comparison group was made with a subset of 44
      of the 678 women who showed a normal tolerance test. No group differences were
      seen in parity, and age, nor in body weight gain or changes in body mass index,
      the latter measured in the initial and final weeks of pregnancy. Significant
      differences versus the normal women were seen in the GD group for cesarean births
      (43% vs 30%) and in macrosomy (25% vs 7%). The group with one abnormal test
      showed high values in cesareans (50%) and macrosomy (10%) but did not reach
      significant difference with the other groups. CONCLUSIONS: GD was higher in our
      study than in the only paper on GD prevalence reported in Mexico (3.9%). The
      higher incidence of cesareans and macrosomy in GD makes it necessary to consider
      therapeutic interventions in these cases.

PMID- 8134727
TI  - [Treatment of paroxysmal nocturnal hemoglobinuria with antilymphocyte globulin].
AB  - OBJECTIVE: To evaluate the effectiveness of antilymphocyte globulin therapy (ALG)
      in patients with paroxysmal nocturnal hemoglobinuria (PNH). DESIGN: Prospective,
      non-controlled trial. SETTING: Hematology Service, Hospital de Especialidades,
      Centro Medico Nacional Siglo XXI, IMSS, Mexico City. PATIENTS: Six patients were
      included. The median age was 37.5 years and the male/female ratio was 1:1. All
      the patients had clinical disease consistent with PNH (hemolytic anemia with some
      degree of transient or persistent pancytopenia) and also erythrocytes with
      enhanced sensitivity to complement mediated lysis in vitro, as documented by
      either the Ham test or the sucrose lysis assay. The criterion for severity was
      the existence of continuous hemolysis in all and transfusion requirements of two
      or more packed red cells per month in four cases. Prior to ALG therapy, androgens
      and/or steroids had been given to five patients with no improvement.
      INTERVENTION: A single batch of ALG was used during the trial (E 0034,
      Lymphoglobulin Merieux, Lyon, France). Patients received an infusion of 10 mg/kg
      per day in a 20 hours lapse during four consecutive days. Also 500 mg/day of
      methylprednisolone were started simultaneously with the ALG; it was given for
      seven days and was gradually tapered off and stopped on day 30. MEASUREMENTS: The
      increases in hemoglobin, granulocytes and/or platelets as well as decreases in
      red cell transfusion requirements were used to evaluate the results of therapy.
      RESULTS: Two patients suffered anaphylaxis after the first administration of ALG
      and were withdrawn from the study. Two of the four remaining patients responded,
      one response was total and the other minimal. The responses were transient, and
      no response was seen in the follow-up of 11-14 months. CONCLUSION: ALG therapy
      for PNH in the doses and time periods used by us had no beneficial effect in
      patients with a severe form of PNH.

PMID- 8134728
TI  - [The international normalization ratio in the monitoring of oral anticoagulant
      therapy].
AB  - Oral anticoagulants are employed very frequently in the prophylaxis and treatment
      of several diseases. For their optimal effectiveness, many vigilance schedules
      have been proposed but none has proved to be 100% effective. The international
      normalization ratio (INR) can be a safer way to monitor oral anticoagulation, and
      our objective was to determine its clinical usefulness. A prothrombin time test
      (PT) was carried out by means of either a chromogenic or a coagulometric method,
      and an INR was obtained using the ratio of the PT patient/PT control elevated to
      an exponential given by the international sensitivity index (ISI) of our
      thromboplastin. Our objective was to maintain our patients in a therapeutical INR
      range between two and three. We present our experience with 77 patients and 810
      results during an 18 months period. We observed 26 cases of hemorrhage and three
      of thrombosis. In all these cases, the INR was out of the desired therapeutical
      range. No deaths occurred in our patients. Our analysis showed a significative
      disagreement between the INR and the prothrombin time ratio (PTR) but a better
      correlation with hemorrhage and thrombosis was seen with the INR than with the
      PTR. Our experience supports the use of INR in the clinical vigilance of oral
      anticoagulation as a useful method.

PMID- 8134729
TI  - Clinical usefulness of mean corpuscular volume and red cell distribution width in
      iron deficient blood donors.
AB  - The clinical efficacy of the red cell distribution width (RDW > 14.2%) and the
      mean corpuscular volume (MCV < 83.5 fL) in detecting iron deficiency was
      evaluated in female blood donors. Employing transferrin saturation < 17%, the
      prevalence of iron deficiency in 296 female donors was 23%, and in 635 male
      donors 1.1%. In the total female population, the sensitivity and specificity of
      the indices were 78% and 92%, respectively, but they were higher in anemic
      females (sensitivity 90% and positive predictive value 92%) than in non anemic
      females (sensitivity 58% and positive predictive value 50%). Our results confirm
      that there is an overlap in the levels of RDW and MCV between the iron and non
      iron deficient subjects, and these overlap seems to be more remarkable in the non
      anemic individuals. We conclude that these erythrocyte indices could be useful to
      identify iron deficiency in anemic female blood donors, but not in non anemic
      ones.

PMID- 8134730
TI  - Meningioma-like intracranial granulocytic sarcoma (chloroma). Radiologic and
      surgical findings.
AB  - We present the case of a 23 years old female with chronic granulocytic leukemia
      and two intracranial tumors with all the radiological characteristics of
      intracranial meningiomas. Successful removal of the largest tumor was
      accomplished using the technique described for meningiomas. The recovery was very
      good and the histopathologic diagnosis was of granulocytic sarcoma. Radiotherapy
      of the second tumor reduced the tumor mass within one month leaving the patient
      neurologically intact. We recommended surgery in the future treatment of large
      chloromas.

PMID- 8134731
TI  - [Molecular genetics of colorectal cancer and carcinogenesis].
AB  - Genetic and environmental aspects play an important role in the development of
      colorectal cancer. However, the common molecular alteration in both hereditary
      and sporadic colon cancer is localized in the APC gene. the APC gene maps in the
      long arm of chromosome 5 and was discovered in patients with familial adenomatous
      polyposis (FAP). The search for the APC gene led to the identification of
      restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these
      RFLPs in relatives of FAP patients it is possible to make the presymptomatic and
      prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in
      vivo. Thus the different stages involved in the FAP syndrome which include
      hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have
      allowed the analysis of molecular alterations in oncogenes and tumor suppressor
      genes. The APC gene alteration if not inherited, occurs as the earliest molecular
      alteration in the development of colorectal cancer whereas structural alterations
      of the genes myc, ras, p53, MCC and DCC are considered to be late events. All
      these investigations have lead to 1) a better understanding of the ethiology of
      cancer and 2) early diagnosis of colorectal cancer in both the hereditary and
      sporadic forms of the disease.

PMID- 8134732
TI  - Sample size calculations for ordered categorical data.
AB  - Many clinical trials yield data on an ordered categorical scale such as very
      good, good, moderate, poor. Under the assumption of proportional odds, such data
      can be analysed using techniques of logistic regression. In simple comparisons of
      two treatments this approach becomes equivalent to the Mann-Whitney test. In this
      paper sample size formulae consistent with an eventual logistic regression
      analysis are derived. The influence on efficiency of the number and breadth of
      categories will be examined. Effects of misclassification and of stratification
      are discussed, and examples of the calculations are given.

PMID- 8134733
TI  - Relative risk, risk difference and rate difference models for sparse stratified
      data: a pseudo likelihood approach.
AB  - We consider a relative risk and a risk difference model for binomial data, and a
      rate difference model for Poisson (person year) data. It is assumed that the data
      are stratified in a large number of small strata. If each stratum has its own
      parameter in the model, then, due to the large number of parameters,
      straightforward maximum likelihood leads to inconsistent estimates of the
      relevant parameters. By contrast to the logistic model, conditioning on the
      number of events per stratum does not help in eliminating the stratum nuisance
      parameters. We propose a pseudo likelihood method to overcome these consistency
      problems. The resulting pseudo maximum likelihood estimates can easily be
      computed with standard statistical software. Our approach gives a more general
      framework for the Mantel-Haenszel type estimators proposed in the literature. In
      the special case of a series of 2 x 2 tables, for the risk and rate difference
      models, our approach yields exactly these ad hoc Mantel-Haenszel estimators,
      while for the relative risk model it gives a close approximation of the Mantel
      Haenszel relative risk estimator. For the regression models corresponding to the
      association measures relative risk, risk difference and rate difference, our
      method provides analogues of conditional logistic regression, which were not
      previously available.

PMID- 8134734
TI  - Cross-validation in survival analysis.
AB  - The predictive value of a statistical model is conceptually different from the
      explained variation. In this paper we construct a measure of the predictive value
      of the Cox proportional hazards model, computed from the leave-one-out regression
      coefficients. These coefficients can also be used to calculate a shrinkage factor
      which can be applied to improve the predictions and that can be used in R2-type
      measures of the proportion of explained variation. Our methods are illustrated by
      a study of chemotherapy for advanced ovarian cancer.

PMID- 8134735
TI  - Plotting summary predictions in multistate survival models: probabilities of
      relapse and death in remission for bone marrow transplantation patients.
AB  - Multistate survival analysis usually involves a series of detailed regressional
      analyses describing transitions between various states. There is an often
      neglected need for the many estimates resulting from such an analysis to be re
      synthesized into summary statements, such as prediction of various outcomes from
      specified patient histories. Arjas and Erola recently proposed a framework for
      dynamic probabilistic causality which has calculation of such prediction
      statements as a central tool. We illustrate these procedures on data from a
      multicentre bone marrow transplantation study, with death while in remission and
      relapse as terminal events and recovery of the patients's platelets to a normal
      level and the onset of acute graft-versus-host disease as intermediate events,
      using Cox regression models throughout. Among the features illustrated by the
      resulting plots is a strong effect on death while in remission if the platelets
      do not recover within the first three months.

PMID- 8134736
TI  - Analysis of case-crossover designs.
AB  - The case-crossover design provides a means to study the effects of transient
      exposures on the risk of acute illness, for example, the effects of drinking
      alcohol on the immediate risk of a heart attack. Only cases are required by the
      design, since each case is effectively its own control; what a case was doing at
      the time of an acute event is compared with what the case would have been doing
      usually. Maclure has described an approach based on the Mantel-Haenszel method of
      analysis. It is shown here how the analysis of case-crossover designs can be
      achieved by a method of maximum likelihood. The method is quite general and, in
      principle, can be used to analyse the joint effects of many transient exposures.
      For binary exposures the Mantel-Haenszel approach is an approximate solution to
      the likelihood equations. In practice, case-crossover designs are limited by the
      information available on each case's 'usual' behaviour. Extracting such
      information requires in-depth questioning, but, in principle, it can be obtained.
      To do so requires careful questionnaire design. The approach is illustrated by
      analysis of 24 hour alcohol consumption and the risk of myocardial infarction.
      The problem with this analysis is how to estimate the probability of what a case
      would 'usually' have been doing from information on drinking frequency.

PMID- 8134737
TI  - Dynamic balanced randomization for clinical trials.
AB  - Common methods of treatment allocation for multi-centre and/or stratified
      randomized clinical trials can result in substantial differences between the
      number of patients allocated to each treatment arm. This can occur in the overall
      trial for a permuted block design or within individual institutions/strata when
      using a minimization scheme. This may lead to a bias in the result. Also, these
      procedures can be predictable, with the possibility of an investigator-introduced
      selection bias. An easily implemented method of randomization is proposed which
      attempts to overcome these problems by balancing treatment allocations both
      within strata and across the trial as a whole. The method keeps a running tally
      on total treatment allocation numbers at all stratification levels. When a
      patient accrues a hierarchical decision rule is applied, and the allocation is
      deterministic if certain pre-defined limits are exceeded, and random otherwise.
      The method is an extension of the big stick design of Soares and Wu, and is
      related to both Zelen's key number randomization methods and the schemes of
      Nordle and Brantmark. Simulation studies are used to demonstrate that major
      imbalances possible with other schemes do not occur using this method, and that
      the potential for selection bias is much reduced.

PMID- 8134738
TI  - Comparison of the Cox model and the regression tree procedure in analysing a
      randomized clinical trial.
AB  - In a clinical trial comparing different treatments the patients may be rather
      heterogeneous with regard to their natural prognosis. Simple overall comparison
      of the treatment groups may lead to a biased estimate of the treatment effect
      even in a well-balanced randomized study, at least when survival time is the
      outcome. An adequate analysis of the treatment effect is only feasible in a
      multivariate framework where the important prognostic factors are accounted for
      and, additionally, treatment-covariate interactions may be evaluated. Analyses
      using the Cox model are compared with alternative approaches based on the
      Classification and Regression Tree (CART) technique. Basic differences between
      these approaches are outlined and discussed in the context of a randomized
      clinical trial of chemotherapy in patients with brain tumours.

PMID- 8134739
TI  - Inherent difficulties with active control equivalence studies.
AB  - A simple model is used to investigate the relevance of 'competence' to active
      control equivalence studies (ACES). It is shown that to the extent that such
      trials are successful the results of such trials must raise doubts regarding
      their competence. ACES are thus more problematic than classical clinical trials
      and the problems with such studies cannot be solved simply by exchanging the
      usual roles of null and alternative hypotheses.

PMID- 8134740
TI  - The relative importance of prognostic factors in studies of survival.
AB  - The relative importance of prognostic factors in regression can be measured
      either by standardized regression coefficients or by percentages of explained
      variation in a dependent variable. One advantage of using explained variation is
      the direct comparability of qualitative prognostic factors with others, or of
      groups of prognostic factors. The description of relative importance can be
      accomplished within marginal or partial effects analyses. It is demonstrated that
      it is possible not only to provide a descriptive ranking of prognostic factors
      according to their statistically determined importance, but also to make
      inferences concerning their relative importance, employing bootstrap techniques
      and procedures for multiple comparisons. The methods presented, which are new in
      the context of Cox regression, are exemplified by analyses of studies of lung
      cancer and breast cancer.

PMID- 8134741
TI  - Alert systems for post-marketing surveillance of adverse drug reactions.
AB  - When monitoring spontaneous reports of adverse reactions to registered drugs, it
      is important to detect any change in the number of reported adverse reactions in
      the course of time. Sales adjusted adverse drug reaction rates are usually
      compared in order to be able to take drug exposure into account. Here we review
      the so-called arithmetic and some statistical procedures which could form the
      basis for an alert system. The advantages and disadvantages of each of these
      methods are discussed. The importance of data requirements and the problems which
      arise when using an alert system are pointed out and then clarified with the help
      of the example of diphtheria/tetanus vaccine.

PMID- 8134742
TI  - Relationships between incidence and mortality in non-reversible diseases.
AB  - The estimation of the incidence of chronic diseases from mortality and survival
      rates is shown to be attainable, under some simplifying hypotheses, through the
      solution of a convolution equation. Exact solutions are derived for the cases in
      which survival times of incident cases are exponential or gamma distributed.
      Applications to breast cancer, HIV infection and stomach cancer incidence in the
      Italian population are presented.

PMID- 8134743
TI  - [What is your diagnosis? Bilateral Achilles tendinitis associated with quinolone
      treatment].

PMID- 8134744
TI  - [Consciousness disorders].

PMID- 8134745
TI  - [Consciousness and self-consciousness as biological phenomena].
AB  - Can there be a generally accepted account of consciousness? Consciousness is the
      main aspect of the mind-body problem and has intrigued man since he achieved the
      awareness of his own existence and identity, i.e. since he became self-conscious.
      The topic of consciousness spans the efforts of the humanist and naturalist,
      psychological, theological and physiological thinking and research. During the
      last years an upsurge of both neurophysiological and philosophical interest has
      tried to outline the place of consciousness and self-consciousness in the order
      of nature. 'Without consciousness, the mind-body problem would be much less
      interesting. With consciousness it seems hopeless', Nagel (16) wrote. Our thesis,
      supported by a significant part of today's epistemology (which takes up the
      believes of several main physiologists from the last century up to now), is that
      the question of consciousness and the mind-body problem are systematically and
      scientifically insoluble because the mind is fated to remain intrinsically
      mysterious to us. Thus, even though consciousness and self-consciousness belong
      to the intrinsic characteristics of our everyday life and experience, they seem
      to remain indefinable and mysterious and, therefore, to fall outside the scope of
      rational inquiry, defying both scientific and philosophical investigation. This
      assumption does not mean that neurophysiological sciences are unfeasible, but it
      is just an inquiry into their methodologic and cognitive limits.

PMID- 8134746
TI  - [Classification and definition of consciousness disorders].
AB  - A classification of the disturbances of consciousness is given, and the possible
      causes are listed. The criteria used in Switzerland for the diagnosis of brain
      death are presented in detail.

PMID- 8134747
TI  - [Neurology of consciousness and of consciousness disorders].
AB  - The two physiologic components of conscious behaviour, namely arousal (vigilance)
      and content of consciousness (presence of mind), may be affected differently,
      depending on the type and distribution of the underlying brain disease.
      Disturbance of arousal primarily affects wakefulness and awareness and leads to
      obtundation, stupor and coma. States of reduced arousal are caused by bilateral
      lesions of the so-called ascending reticular activating system (ARAS), which is
      situated in the upper brainstem and the paramedian diencephalon. If, on the other
      hand, cognitive and mnemic function are degraded, the contents of consciousness
      are disordered; depending on the extent of the disturbance, confusion, lethargy
      and, finally, a vegetative state ensues. The chronic vegetative state (coma
      vigil) describes a condition of total mental loss with preserved vegetative
      functions and arousal. Degraded cognitive and mnenic functions results from
      either toxic-metabolic or extensive structural disorders of the cerebral cortex,
      where the limbic and mesial frontal areas play a dominant role for conscious
      behaviour. If the function of extensive areas of both hemispheres is suddenly
      depressed, temporarily reduced arousal also results. In order to differentiate
      between toxic-metabolic and structural brain diseases, the motor reactions, the
      ocular and the pupillary reflexes must be examined apart from responsiveness.

PMID- 8134748
TI  - [Syncope--incidence, diagnosis and differential diagnosis].
AB  - Syncopes are not rare at all. They are seen in 0.75% of patients of an outpatient
      department of internal medicine, and 0.03% of blood donors have syncopes. In the
      Framingham study, in the course of 26 years 3 to 3.6% of the population had
      syncopes. The diagnosis can be made just by careful questioning and the usual
      physical examination of the patient. In spite of thorough examination, the cause
      of the syncope cannot be determined in 25 to 85% of cases. Among those carefully
      analysed, 5 to 15% are due to a primary cerebral cause and 15 bis 40% are due to
      a cardiovascular problem. Of course selection of patients following the
      institution which made these studies play an important role. We conclude that the
      careful questioning of the patient and, if possible, of witnesses of the syncope
      represents the most important element for diagnosis.

PMID- 8134749
TI  - [Acute confusional states. Analysis of 60 cases observed in a neurological
      department].
AB  - The authors describe the clinical picture, etiology and evolution of 64 patients
      admitted because of an acute confusional state to the Department of Neurology of
      the University Hospital in Lausanne (CHUV) during two years (1991 to 1992). The
      difficulty of clinical diagnosis, particularly in vascular and epileptic cases,
      the high percentage of focal neurological causes, the role of (underlying)
      dementia, drugs, systemic disturbances (fever, infections, dehydration, etc.) and
      the importance of etiology for prognosis are particularly stressed.

PMID- 8134750
TI  - [Examination and observation of the unconscious patient].
AB  - The old neurological art of careful examination and detailed description of an
      unconscious patient delivers a vivid picture of cerebral functions and
      deficiencies. Daily medical practice, however, demands immediate information with
      measurable and easily comparable numerical values. This requirement is best
      satisfied by the current proven and universally accepted 'Glasgow Coma Scale'.
      Dispensing with the terms: somnolent, soporous and comatose, the GCS numerically
      marks the depth of the disturbances of consciousness, which, recorded in a graph,
      indicate the fluctuations of consciousness. The registration of the depth and
      duration of clouded consciousness is a decisive criterion for the prognosis.

PMID- 8134751
TI  - [Pulmonary abscess].

PMID- 8134752
TI  - [Serotoninergic receptors: physiological and therapeutic implications].

PMID- 8134753
TI  - [Retroperitoneal fibrosis].

PMID- 8134754
TI  - [The price of health or health at any price].

PMID- 8134755
TI  - [New medications: azithromycin].

PMID- 8134756
TI  - [Prevention of endometrial carcinoma in postmenopause].

PMID- 8134757
TI  - [Criteria for choice of vaginal hysterectomy for lesions other than invasive
      cancer].
AB  - The authors analyse in retrospect a continuous series of 208 hysterectomies, for
      lesions other than invasive cancer, in order to try to define precise objective
      criteria for the choice of the vaginal way. What essentially commands the choice
      of this way are: high parity, large size of the uterus, the existence of
      prolapsus, effort-linked urinary deficiency and no annexial pathology.

PMID- 8134758
TI  - [Residual ovary after hysterectomy. Is castration at peri-menopause necessary to
      prevent ovarian cancer?].
AB  - OBJECTIVE: Evaluation of the risk of ovarian carcinoma associated with uni or
      bilateral adnexal preservation following gynecological surgery for benign
      lesions. MATERIAL: Gynecological surgery history of 190 patients with a primary
      ovarian carcinoma diagnosed and/or treated in the Navarre Teaching Hospital Group
      between 1981 and 1991 inclusive. RESULTS: Two patients, i.e. 1%, had undergone
      conservative surgery prior to the diagnosis of ovarian neoplasia. CONCLUSION:
      Ovary left in place after conservative surgery undergoes malignant change less
      than in the population as a whole.

PMID- 8134759
TI  - [Pregnancy in a rudimentary uterine horn: main clinical forms. 5 cases].
AB  - Five cases of pregnancy developing in a rudimentary uterine horn are reported.
      The incidence of this association is 1/40,000 pregnancies. Three patients
      underwent surgery in a context of massive intraperitoneal bleeding due to rupture
      of the uterus during the second three months of pregnancy. Pregnancy continued
      into the third three months in 2 patients. The diagnosis was made at laparotomy,
      the uterus having ruptured in both cases. In the first case, rupture was
      clinically silent with development of the fetus in the abdominal cavity. In the
      second case, the pregnancy stopped developing at 34 weeks after the LMP.
      Histological examination of hemi-hysterectomy specimens showed that the placenta
      was accreta in all cases. Analysis of these 5 cases and a review of the
      literature form the basis of a review of the current contribution of
      investigations to the diagnosis of this association.

PMID- 8134760
TI  - [Pregnancy in a rudimentary uterine horn: rupture in the 15th week of
      amenorrhea].
AB  - A case of pregnancy in a rudimentary uterine horn with rupture 15 weeks after the
      LMP is described. Ultrasonography at the beginning of such a pregnancy should
      allow the diagnosis of these uterine malformations. Closer monitoring of the
      pregnancy is necessary because of the seriousness of potential complications. The
      frequent finding of placenta accreta in such situations is pointed out.
      Management approaches are described.

PMID- 8134761
TI  - [Simultaneous pregnancy in each cavity of a bicornuate bicervical uterus with a
      double vagina].
AB  - A case of twin pregnancy in a bicervical uterus with double vagina is reported.
      The malformation was known before conception. Caesarean section was performed for
      premature rupture of the membranes at 34 weeks. This enabled the extraction of
      two low-birth-weight premature infants free of any particular pathology. The
      possibility of twin pregnancy in a bicervical bicornuate uterus is 1/1,000,000
      and implies the maturation of at least two oocytes. This is a high risk
      pregnancy. Spontaneous abortions, prematurity (40%), low-birth-weight (25%) are
      the most notable complications. Although the probability of dynamic dystocia is
      multiplied by 7, vaginal delivery is not excluded when the obstetric past history
      is satisfactory and the presentation of both twins cephalic. Caesarean involves
      hysterotomy of each horn and raises no special technical problems. Double
      delivery increases the risk of hemorrhage.

PMID- 8134762
TI  - [Pregnancy in the uterine horn after total salpingectomy].
AB  - The authors report a case of pregnancy of the uterine horn occurring after total
      salpingectomy, i.e. including resection of the intramural portion of the tube.
      They identify the epidemiological, pathophysiological and clinical features of
      this complication with the help of a review of the literature of cases occurring
      after partial salpingectomy and total salpingectomy. They discuss the usefulness
      of resection of the interstitial portion of the tube and feel that prophylactic
      cesarean section is justified in patients who have remained fertile.

PMID- 8134764
TI  - [Report on the status of the world population].

PMID- 8134763
TI  - [Recurrent acute hepatic steatosis in pregnancy].
AB  - Acute fatty infiltration of the liver in pregnancy (AFILP) is a rare disorder
      with a severe prognosis, improved by diagnosis of the minimally symptomatic form.
      AFILP is classically considered to be non-recurrent. We nevertheless report the
      fourth case of the recurrent form.

PMID- 8134765
TI  - [Transvaginal colposuspension. A series of 49 cases].
AB  - Retrospective study from january 1991 to May 1993 of 49 patients undergoing
      transvaginal colposuspension (TVC) for urinary stress incontinence (USI).
      SURGICAL TECHNIQUE: 14 TVC performed using Raz's technique, including 11 with non
      absorbable suture material. 35 TVC were performed by longitudinal incision,
      including 26 with non-absorbable suture material. RESULTS: Peroperative
      complications: 3 accidental bladder lesions (6.1%), 2 hemorrhages during
      detachment of Retzius (4%). Postoperative complications: temperature over 38
      degrees in 10 cases (17%), 3 urinary tract infections (5.1%), 1 phlebitis (post
      sacro-spino-fixation). Functional results: 3 early failures at 2 months (93.9%
      good results). TVC is a simple technique for dealing with USI but longer follow
      up is necessary for its invalidation.

PMID- 8134767
TI  - Crude or recombinant proteins applied to latex agglutination, complement fixation
      and enzyme-linked immunosorbent assays for the serodiagnosis of invasive
      amebiasis.
AB  - Three different agglutination tests were developed for the detection of serum
      antibodies against Entamoeba histolytica. These tests are based on carboxylated
      polystyrene beads loaded either with a purified recombinant E. histolytica
      protein, designated recEh-P1, or a soluble fraction, or a membrane fraction (M
      LA) both prepared from E. histolytica trophozoites. The three agglutination tests
      were compared with an enzyme-linked immunosorbent assay and a complement fixation
      test based on crude soluble E. histolytica antigens as well as with an enzyme
      linked immunosorbent assay using recEh-P1 as antigen (P1-EIA). Serum samples from
      patients with invasive amebiasis (n = 30), or infectious diseases unrelated to E.
      histolytica (n = 57), as well as sera of apparently healthy individuals (n = 25)
      including some with noninvasive amebiasis (n = 5) were analysed by all six
      methods. Depending on the assay used, the results obtained, revealed
      sensitivities ranging from 83% to 100% and specificities ranging from 93% to
      100%. P1-EIA and M-LA exhibited best results, both with a sensitivity of 100% and
      a specificity of 98%.

PMID- 8134766
TI  - Experimental infections of Anopheles gambiae with Plasmodium falciparum of
      naturally infected gametocyte carriers in Cameroon: factors influencing the
      infectivity to mosquitoes.
AB  - Factors which could influence the success of experimental infections of Anopheles
      gambiae with Plasmodium falciparum were investigated in Cameroon. 139
      experimental infections with different gametocyte carriers were performed. 86
      (62%) gave rise to mosquito infection after dissection of at least 20 mosquitoes.
      Among succeeding infections, the mean percentage of infected mosquitoes was 18.6%
      and mean oocyst load per positive midgut was 2.56. Only gametocyte density was
      identified as a factor which determined the success and the level of mosquito
      infection. No significant influence was found for sex and age of the gametocyte
      carrier, body-temperature, presence of asexual erythrocyte stages, rhesus factor,
      blood group and use of antimalarial drugs (chloroquine and amodiaquine).

PMID- 8134768
TI  - Glycosome-associated tyrosine-phosphorylated protein in Trypanosoma brucei.
AB  - Phosphorylation of protein at tyrosine residues is an important mechanism for
      regulating protein function in eukaryotic cells. In this report we have
      identified by immunoblotting the target for tyrosine phosphorylation in the
      protozoan parasite Trypanosoma brucei as a doublet band of protein with molecular
      masses of 200 and 220 kDa. Ultrastructurally, the tyrosine-phosphorylated protein
      was localized to the microbody-like organelles unique to kinetoplastid protozoa,
      called glycosomes. Inhibition of multiplication by the tyrosine kinase inhibitor
      genistein appeared to have very different kinetics in procyclic and blood-stream
      stage parasites. This is consistent with a glycosomal location for the target of
      tyrosine kinase as these life cycle stages differ substantially in their
      dependence on glycolysis which occurs in this organelle.

PMID- 8134769
TI  - Prevalence of Chagas' disease in Ayoreo communities of the Paraguayan Chaco.
AB  - The prevalence of Chagas' disease in Ayoreo amerindians living in their
      traditional habitat of the Paraguayan Chaco was assessed by ELISA and indirect
      immunofluorescence techniques. The Ayoreo is the last hunther-gatherer tribe of
      the Paraguayan Chaco and was "pacified" between 1965 and 1975. They still
      maintain a seminomadic way of life. Chagas' disease prevalence in the Ayoreo
      communities probably represents their natural prevalence in Chaco Amerindians
      before settlement. Triatoma sordida was identified as the insect vector in the
      settlements of Gesudi and Chovoreca, while the highly domiciliary Triatoma
      infestans was found in Campo Loro. The prevalence of Chagas' disease in Gesudi
      and Chovoreca, based on our serological surveys was 12-13%. Other authors
      reported a 72.9% of Chagas' disease prevalence in amerindians settled in the
      Chaco since 1930-1940.

PMID- 8134770
TI  - Histochemical distribution of esterases in adult Onchocerca fasciata
      (Filarioidea: Onchocercidae).
AB  - The localization and distribution patterns of non-specific esterases (NSE) and
      acetylcholinesterase (AChE) activities in adult female Onchocerca fasciata
      (Filarioidea: Onchocercidae) have been determined using enzyme histochemical
      techniques. NSE activity was highest in the hypodermis and mild to moderate in
      the somatic musculature and uterine epithelium. The intensity of the reaction was
      decreased but not eliminated by sodium fluoride. AChE activity was found in the
      hypodermis and cuticle of the female worm, highest in fully formed microfilariae
      in the uterus, whereas early oocytes and embryonic forms were negative.
      Butyrylcholinesterase activity showed similar but less intense staining reactions
      at the same sites. Eserine-treated sections showed no AChE activity in all areas
      where it is usually present. The present techniques failed to demonstrate AChE
      activity in the nervous tissue including the hypodermal nerve trunks and
      neuromuscular junctions of the worm. The possible functional significance of the
      demonstrable enzymes was discussed with respect to their location. NSE activity
      may be involved in lipid metabolism, whereas AChE activity may have a role in
      host-parasite relationship.

PMID- 8134771
TI  - Turnover of microfilariae in small mammals. 1. Disintegration of microfilariae
      (Litomosoides sigmodontis) (Filarioidea: Nematoda) after intravenous injection
      into Sigmodon hispidus, the cotton rat.
AB  - After i.v. injection of 833 x 10(3) microfilariae (mf) per animal (150 g) into
      naive recipient cotton rats, at autopsy 15 min thereafter 30.4% of them could be
      recovered as a total: 19.1% were proved in the peripheral circulating blood (PCB)
      completely intact. 6.5% were recovered by perfusion of the lungs, of which 3/5
      were associated with adherent macrophages and neutrophils or partly
      disintegrated. By perfusion of the liver only 3.8% were obtained, in spite of the
      four times greater volume of blood, of which 2/3 had adherent cells or were
      partly disintegrated. 0.7% and 0.3% were recovered from kidneys and spleen,
      respectively. In patent animals with adult worms the permanently delivered mf
      were distributed as follows: 41.6% were proved in the PCB; by perfusion 19.1%
      were obtained from the lungs and 32.9% from the liver; the rest of 6.4% were
      found in kidneys and spleen. In the capillary systems of lungs as well as the
      liver the proportion of normal mf (1/3), with adherent cells (1/3), partly
      disintegrated ones (1/5) and fragments (1/20) were quite similar. In long term mf
      injection experiments using the same dosage the autopsy was done 30 min and 1, 2,
      3 and 28 days p. inj. of mf into naive animals. 30 min p.inj. 56% of the mf
      injected could be recovered as a total: 28.6% were obtained from the PCB, 16.0%
      from the lungs and 7.1% from the liver as normal mf (no perfusion), the rest of
      4.1% from heart muscle, kidneys and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134772
TI  - How long do the effects of ivermectin on adult Onchocerca volvulus persist?
AB  - The persistence of the effects of ivermectin on the viability, morphology and
      reproductivity of adult Onchocerca volvulus was examined eighteen months after
      treatment with a single or five six-monthly doses of ivermectin and compared with
      untreated controls. Treated nodules were removed from patients participating in a
      randomised controlled trial of ivermectin in Sierra Leone. Adult filariae, 545
      females and 348 males, were isolated by collagenase digestion. The nodules were
      significantly smaller, contained fewer young worms and supported lower
      microfilarial production in those treated with five doses of ivermectin. The
      productivity index, a measure of the reproductive potential of a worm population,
      was still reduced by 83% eighteen months after five doses and by 63% after a
      single dose compared to controls. These results show that worms recover their
      fertility even after multiple doses of ivermectin, but do so slowly compared to
      standard dosage intervals. In addition ivermectin may have a partial
      chemoprophylactic effect which contributes to the maintenance of low
      microfilarial production in conditions of on-going transmission.

PMID- 8134773
TI  - Parasitological and clinical characterization of Simulium neavei-transmitted
      onchocerciasis in western Uganda.
AB  - In the forests of western Uganda onchocerciasis is transmitted by Simulium neavei
      s.s. Since little is known about the infection transmitted by this vector, a
      survey was made in 1991 with special regard to adult persons of 15 years and
      older in the 13 villages of the parish Kigoyera 40 km northeast of Fort Portal.
      3268 (52%) of the 6271 registered inhabitants were examined clinically and
      parasitologically. The highest microfilaria (mf) densities were found on the
      buttocks, lower ones on the shoulders and the lowest on the ankles. In the parish
      the standardised prevalence of mf carriers was 62%. The crude prevalences of
      adult mf carriers ranged from 80% to 95% in the 13 villages. Densities of 100
      mf/snip or more were found in 25% of male persons. The community microfilarial
      load (CMFL) in skin snips from the buttocks was 49 mf/snip, ranging from 22 to 93
      in the 13 villages. The standardised prevalence of nodule carriers was 25% and
      the mean nodule load was 1.9 nodules per nodule carrier. Among 3420 nodules 90%
      were found on the pelvic girdle. The standardised prevalence of onchocercal
      dermatitis was 19%. The crude rates ranged within the age groups in males from
      20% to 45% and in females from 16% to 41%. The standardised prevalence of persons
      presenting mf in the anterior chamber of the eye was 24% and the CMFL in the
      anterior chamber ranged between 1.2 and 3.3 mf/chamber in six villages.
      Standardised rates were 1.6% for sclerosing keratitis and 0.9% for reduced vision
      of 3/60 or less. These prevalences of eye lesions are comparable to those
      observed in West African forest areas. The CMFLs and the prevalences of mf and
      nodule carriers represent suitable criteria for community diagnosis of S. neavei
      transmitted onchocerciasis in Uganda to guide ivermectin treatment, whereas the
      prevalence of "leopard skin" is not useful. Immigrants living less than five
      years in the endemic focus should be excluded from the assessment of mf carrier
      rates and those living there less than ten years from rapid assessment of nodule
      carrier rates.

PMID- 8134774
TI  - Effects of sensitization on efficacy of mebendazole in mice infected with adult
      Angiostrongylus costaricensis.
AB  - The relation between immunopotentiation and efficacy of mebendazole in sensitized
      mice infected with adult Angiostrongylus costaricensis was investigated. When
      compared with the non-treated control, the sensitized control showed better
      results in almost all parameters with a few mice being positive for the first
      stage larvae in feces and eggs in the intestinal section. The results suggest
      development of protective immunity in the sensitized mice though it was not
      completely effective for inhibiting infection, worm growth and their functions.
      The immunity seemed to be developed by producing specific antibodies against the
      larvae by sensitization. Among 4 infected groups, the sensitized-treated group
      had the best results in all parameters especially in worm recovery and worm body
      length which referred that drug action was enhanced by the sensitization.

PMID- 8134775
TI  - Spleen rupture in a patient with dengue fever.
AB  - A case of rupture of the spleen is described secondary to dengue 1 fever in an
      adult patient. This exceptional complication occurred during an outbreak of
      dengue in French Polynesia. After failure of conservative management, splenectomy
      was performed. Examination of the surgical specimen confirmed softening and
      enlargement organ with the formation of a subcapsular hematoma.

PMID- 8134776
TI  - Disposable environmental chamber for assessing the drug susceptibility of malaria
      parasites.
AB  - The CO2-enriched atmosphere required for the short-term growth of human malaria
      parasites can be provided by a small, disposable environmental bag that is
      readily available in many laboratories. This provides an ideal alternative means
      for incubating malaria parasites when specially-prepared gas mixtures, air-tight
      incubation chambers or candle-jars are unavailable or they are too expensive or
      impractical to use. Such an environmental bag should encourage greater use of the
      WHO in vitro test for assessing the drug susceptibility of malaria parasites.

PMID- 8134777
TI  - Comparison of ivermectin and benzyl benzoate for treatment of scabies.
AB  - A randomized investigator-blinded trial of oral ivermectin 100 micrograms/kg
      single dose vs. benzyl benzoate 10% application in the treatment of scabies, was
      conducted in 1992 in French Polynesia. In total, 44 patients aged 5-56 years were
      included in the study: 23 in the group ivermectin (IVER) and 21 in the group
      benzyl benzoate (BB). At day 30 after treatment, the cumulative recovery rates
      were 70% (16/23) in the group IVER, and 48% (10/21) in the group BB, 95%
      confidence intervals 51-87% and 29-70% respectively. The rates of recovery were
      greater in the group IVER at day 7, 14 and 30, but the difference was not
      statistically significant. Our results show that oral ivermectin is a valuable
      alternative to benzyl benzoate local treatment.

PMID- 8134778
TI  - Long-term efficacy of single-dose treatment with 400 micrograms.kg-1 of
      ivermectin in bancroftian filariasis: results at one year.
AB  - In April 1992, a safety trial was performed with a single dose of ivermectin 400
      micrograms.kg-1 (IVER 400). In 37 bancroftian filariasis carriers, 6 and 12
      months after IVER 400 treatment, the microfilaremia recurrences were 3.2% and
      13.5%, respectively. As compared to results from other studies with
      diethylcarbamazine and IVER at different dosages and periodicities, the dosage of
      IVER 400 seems the most effective; but a yearly intake might not be sufficient.

PMID- 8134779
TI  - Schistosoma mansoni: determination of the sex of cercariae using a
      nonradioactively labelled DNA probe.
AB  - Cercarial sex determination protocol which utilizes nonradioactive nucleic acid
      labelling with digoxigenin (DIG)-11-dUTR, offers a rapid "clean" identification
      of the sex of Schistosoma mansoni cercaria. DIG labelled pW1-DNA (plasmid female
      specific genomic DNA clone--W1) hybridized with the native cercarial DNA, and
      hybridization signals are visualized with Lumigen PPD. Results obtained are
      comparable with those obtained with the 32P labelled pW1.

PMID- 8134780
TI  - The Onchocerca volvulus mRNAs for a hsp70, a collagen-like protein and a
      ribosomal protein possess a 5' spliced leader sequence.
AB  - To detect and analyse Onchocerca volvulus mRNAs possessing a spliced leader (SL)
      sequence, a SL cDNA library was constructed from O. volvulus RNA using a PCR
      method. Three of the sixty cDNAs analysed displayed significant homology to a
      known sequence. These cDNAs encode a hsp70, a collagen-like protein and a 60S
      ribosomal protein. The remaining cDNAs analysed either encoded proteins with no
      apparent homology to known sequences or they appeared to be generated from RNAs
      with an internal SL and did not possess an open reading frame.

PMID- 8134781
TI  - [Physiopathology of acute alcoholic intoxication and alcoholic withdrawal].
AB  - Ethanol blood levels are the result of alcohol absorption and the process of its
      distribution, metabolism and excretion. Kinetics are complex and not yet well
      known. They can be influenced by acquired factors (type of alcohol ingested,
      association with fasting or eating, induction or inhibition of ethanol
      metabolism) or by genetically determined differences in the activity of alcohol
      and of acetaldehyde dehydrogenase. The presence of ethanol in the organism leads
      to various consequences. On the one hand, hydropic changes on membranes modify
      their function and thus that of membrane proteins (particularly receptors); on
      the other, ethanol can affect neurotransmitter metabolism. Such modification of
      the major neurotransmitter systems (cholinergic, aminergic and GABA) in some
      cerebral regions explains the pharmacologic consequences of acute alcohol
      ingestion. In chronic alcohol dependence, adaptation phenomena occur, in both the
      membranes (increased rigidity) and the neurotransmitter systems. They are
      reflected by the hyperexcitability (catecholaminergic hyperactivity and GABA
      hypoactivity) observed after disappearance of the tranquilizing effect of ethanol
      and are clinically expressed by the withdrawal syndrome.

PMID- 8134782
TI  - [Acute ethyl alcohol intoxication].
AB  - Excessive intake of ethyl alcohol leads to acute intoxication and necessitates
      the same management as other forms of intoxication. Diagnosis is based on
      clinical examination, medical history and course. Determination of alcohol level
      in the expired air is of limited interest. If low or absent, it should direct
      clinical investigation toward a disorder having similar symptoms; if high, it
      does not necessarily explain the clinical picture. The severity of the
      intoxication must always be assessed carefully. Severity is linked either to a
      complication of acute alcohol intoxication (coma, inhalation, pneumopathy), or to
      an associated disorder, observed in 50% of the patients (cranial trauma, drug
      intoxication). Means of treatment and patient management are simple and well
      established.

PMID- 8134783
TI  - [Severe somatic complications of acute alcoholic intoxication].
AB  - Acute alcohol ingestion can affect life expectancy and is directly responsible
      for 3,500 deaths per year. Acute lung diseases are mainly caused by pneumococci,
      Gram negative bacilli and anaerobic germs, and are often due to multiple
      microbes. In this case, evolution toward abscess can be feared. Septicaemia and
      enterobacterial peritonitis are frequently observed in cirrhotic patients.
      Ethanol, hypokaliemia and hypophosphoraemia also lead to rhabdomyolysis.
      Rhabdomyolysis can be complicated with acute renal failure and hyperkaliaemia.
      Alcoholic ketoacidosis and the hypoglycaemia favored by prolonged inadequate
      nutrition, are corrected by infusion of glucose solutions. Hyponatraemia can be
      complicated by convulsions and central pontine myelinolysis. Minor forms of
      alcoholic hepatitis remiss after stopping alcohol intoxication. The major forms
      can evolve toward fatal encephalopathy; treatment with corticosteroids improves
      the prognosis in severe hepatitis. The cardiac failure with lactic acidosis in
      shoshin beriberi rapidly evolves to collapsus; treatment is based on emergency
      administration of vitamin B1. Management of patients in acute alcohol episodes
      requires great vigilance. Careful clinical examination and biological tests
      should eliminate severe somatic complications before concluding to simple
      alcoholic intoxication.

PMID- 8134784
TI  - [Convulsive seizures of alcoholics in emergency situation].
AB  - Current medical practice in emergency rooms and epidemiologic studies show that
      ethylalcohol abuse both induces alcohol-related seizures and promotes seizures of
      other origin. Careful neurological examination, particular clinical signs and
      evolution over the first 24 hours constitute the first stage of the diagnosis.
      Only brain CT scan establishes the real cause of the seizures. Treatment of
      seizures is at first aetilogic. In alcohol-related seizures, the alcoholic
      condition does not warrant the use of anticonvulsivants. Abstinence prevents
      alcohol-related seizures while the persistence of the intoxication leads to
      hazardous observance of drug intake.

PMID- 8134785
TI  - [Neurologic emergencies in acute alcoholic intoxication].
AB  - Neurologic complications of acute alcohol intake are less well known to the
      general practitioner than those punctuating the course of chronic alcohol
      dependency. The state of ebriety is a poor incentive to precise neurologic
      analysis and follow-up. Nevertheless, only such surveillance in acute
      intoxication can distinguish a specific neurological complication, a complication
      following a fall or prolonged immobilisation, or rapid decompensation of
      alcoholic encephalopathy. Among the specific complications, myopathies and
      strokes are described here because of their rarity compared to the more common
      epilepsy and withdrawal syndromes. The neurologic semiology of ebriety is
      reviewed, including recent pathophysiological acquisitions specifying the
      mechanism of functional disorders in regions susceptible to alcohol such as the
      cerebellum and the reticular formation.

PMID- 8134786
TI  - [Psychiatric emergencies in acute alcoholic intoxication].
AB  - Acute alcohol ingestion can lead to psychiatric emergencies. The main syndromes
      observed are states of agitation, acute anxiety episodes and suicide or attempted
      suicide. States of agitation are mainly due to simple or pathological inebriety.
      Any case of acute alcoholic intoxication requires a full clinical examination and
      a simple laboratory work-up. Behavioral disorders linked to pathological
      inebriety can be improved by moderate doses of sedatives such as benzodiazepine,
      carbamate, tetrabamate or neuroleptic drugs for the most agitated states. States
      of anxiety generally regress with non-neuroleptic tranquilizers, and attempted
      suicide mainly requires close surveillance or intensive care.

PMID- 8134787
TI  - [Alcohol withdrawal syndrome and delirium tremens. Their treatment].
AB  - The clinical picture of alcohol withdrawal syndrome lies somewhere on a continuum
      that ranges from slight morning tremor to genuine delirium tremens. The
      diagnosis, usually easy, may be beset with several traps: alcoholism may be
      unrecognized, or a diagnosis other than withdrawal syndrome may be wrongly made,
      or again a complication may be either overlooked or erroneously suspected. An
      acute withdrawal syndrome normally regresses in less than one week, but a
      subacute withdrawal syndrome, which presents as signs of residual
      hyperexcitability of the central nervous system, must be recognized, as it may
      persist for several months. Beside delirium tremens, with its mandatory and well
      established treatment, prevention of alcohol withdrawal syndrome and treatment of
      its initial stages raise no problems, as it consists above all of psychotherapy
      combined by such tranquillizers as febarbamate or a benzodiazepine taken in well
      specified dosage.

PMID- 8134788
TI  - [Acute alcoholic intoxication and accidents].
AB  - Many studies have shown the role of alcohol intake, even in low quantities, as a
      risk factor in accidents, mainly road accidents, but also in accidents occurring
      in the home and at the workplace. For a blood alcohol level of 0.5 g per litre,
      the risk of accident is already two-fold. Accidents occur more often to persons
      who drink occasionally than to those who are alcohol-dependent. For a subject of
      average body weight, it is accepted that one glass of an alcohol-containing drink
      can raise the blood alcohol level by approximately 0.2 g per litre. One to two
      hours is required to eliminate this quantity of alcohol.

PMID- 8134789
TI  - [Medicolegal aspects of acute alcoholic intoxication].
AB  - The medico-legal aspects of acute alcohol intoxication mainly concern driving
      while under the effect of alcohol and the regulation thereof. In France, the
      legal limit is 0.8 mg of alcohol per litre of blood and 0.4 mg per litre of
      expired air. Examination is made by breathalyser on expired air. In the blood,
      measurement is performed by oxidation-reduction or gas chromatography, and in the
      expired air, by alcoholometry. Determination of the level of blood alcohol
      remains only approximate and a minimal indicator, given the variable number of
      factors that may intervene.

PMID- 8134790
TI  - [Low frequency positive-pressure ventilation and extracorporeal CO2 removal.
      Treatment of acute respiratory distress syndrome in adults].

PMID- 8134791
TI  - [Holter monitoring of blood pressure. What can be expected?].

PMID- 8134792
TI  - [Physiopathology of cancer of the pancreas. Cancer of the exocrine pancreas: role
      of oncogenes and basic fibroblast growth factor].

PMID- 8134793
TI  - [Vectorization of drugs. A winsome concept with delicate practical applications].

PMID- 8134794
TI  - [Biology of aging].
AB  - The biology of aging, a modest branch of medical sciences at the beginning of
      this century experienced a considerable development as a result of the importance
      and urgency of problems it has to solve. In this short review only a schematic
      presentation of this science can be tempted. Clinical epidemiological studies
      revealed the differential decline of quantifiable physiological functions with
      quite different kinetics. The fastest decline was noticed for the elastic tissues
      such as the lung and the blood vessels, both rich in extracellular matrix (ECM),
      that is connective tissues. Such tissues contain cells able to proliferate
      (mitotic cells) and extracellular matrix. Aging studies of such tissues should
      thus comprise the analysis of cellular aging and the aging of the ECM as well as
      the age-dependent modifications of cell-matrix interactions. The "Hayflick limit"
      is the limited number of population doubling for such cells in culture is obeyed
      by the cells of these tissues. It appears however that this limit is not reached
      during the actual life time of our species. The mechanisms underlying this limit
      at the level of the genome are now actively studied and start to be understood.
      The age-dependent modifications of the relative rates of biosynthesis of ECM
      macromolecules appears to be regulated independently of cell proliferation. Post
      synthetic matrix undergoes also age-dependent modifications such as crosslinking
      attributed to the Maillard reaction, proteolytic degradation and free radical
      damage. The result is a progressively modified ECM in its structure and
      function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134795
TI  - [Acquired data on the antibiotic treatment of bacterial endocarditis on native or
      prosthetic valves].
AB  - Antimicrobial therapy of infective endocarditis is based on periodically updated
      expert recommendations that derive from both clinical and experimental data.
      Streptococcal and enterococcal endocarditis should be treated intravenously with
      a combination of penicillin+aminoglycoside in the absence of allergy to
      penicillin. The choice of either penicillin or ampicillin, the dose and the
      length of treatment plainly depend on susceptibility of streptococcal strain to
      penicillin. In patients allergic to penicillin, vancomycin is the optimal choice.
      The treatment of native valve meticillin-susceptible staphylococcal endocarditis
      is based on a combination of oxacillin or cefamandole+aminoglycoside. Vancomycin
      is recommended in case of allergy to penicillin and in meticillin resistant
      staphylococcal endocarditis. Prosthetic valve staphylococcal endocarditis are
      often due to meticillin-resistant coagulase negative staphylococci. Therefore
      they should be treated with vancomycin in combination with rifampicin and an
      aminoglycoside unless the strain is resistant to either of these 2 antibiotics.
      For the treatment of culture-negative endocarditis, different situations should
      be considered: in native valve endocarditis, the possible responsibility of
      deficient streptococci justifies an ampicillin+aminoglycoside combination; in
      recently implanted (< 1 year) prosthetic valve endocarditis a combination of
      vancomycin+rifampicin+aminoglycoside should be used because of the high
      probability of meticillinresistant staphylococci: if prosthetic valve is
      implanted for more than a year endocarditis may be due to streptococci,
      staphylococci and fastidious gram-negative bacilli; a combination of
      vancomycin+aminoglycoside +/- third generation cephalosporin is therefore
      recommended.

PMID- 8134796
TI  - [Myogenous or muscular syndrome. Diagnostic orientation].

PMID- 8134797
TI  - [Non-traumatic spinal cord compression. Etiology, physiopathology, diagnosis,
      treatment principles].

PMID- 8134798
TI  - [Acute lymphoblastic leukemia in children. Diagnosis, course].

PMID- 8134799
TI  - [Pulmonary tuberculosis and primary tuberculous infection. Epidemiology,
      diagnosis, course, treatment, prevention].

PMID- 8134800
TI  - [Pulmonary pneumocystosis and cerebral toxoplasmosis in patients with HIV
      infection. Diagnosis, course and treatment].

PMID- 8134801
TI  - [Normal childbirth and delivery. Clinical signs].

PMID- 8134802
TI  - [Ulceration or erosion of the oral or genital mucosa. Diagnostic orientation].

PMID- 8134803
TI  - Swedish Association of Urology. Proceedings of the annual meeting. Stockholm,
      December 1-3, 1993.

PMID- 8134804
TI  - Pulmonary hypertension in intensive care: pathophysiology and causes.
AB  - Pulmonary hypertension is commonly encountered in Intensive Care Units and the
      effects on right ventricular function are often a cause for concern. The major
      thrust of treatment must, in the first instance, be aimed at the condition
      causing the hypertension. Treatment with vasodilator drugs may result in systemic
      hypotension which may impair coronary blood flow to the right ventricle, and may
      also result in an impairment of gas exchange. The inhalation of nitric oxide is
      an interesting new approach to treatment, but its value has not yet been
      evaluated in randomized controlled trials.

PMID- 8134805
TI  - [Invasive and non-invasive diagnosis of pulmonary hypertension in the intensive
      care unit].
AB  - The diagnosis of chronic primary and secondary pulmonary hypertension is
      difficult. Important indications result from physical examination and the
      patient's history. Non-invasive diagnostic tools are chest X-ray, ECG, blood gas
      analysis and 2-D-Doppler-echocardiography. If, despite these investigations, no
      reason for the pulmonary hypertension is found, perfusion scintigraphy of the
      lungs and a right-heart catheter investigation should be performed. If there is
      no intracardiac shunting and perfusion scintigraphy of the lungs is normal,
      repeated pulmonary embolism must be excluded by pulmonary angiography. Only after
      elimination of this possibility can primary pulmonary hypertension be regarded as
      the reason for the patient's condition. Pulmonary hypertension is usually more
      acute in the critically ill patient. Under these circumstances, only direct
      pressure measurements are of clinical relevance. In the critical care setting,
      many of the non-invasive methods are either difficult to perform or hard to
      interpret. Furthermore, many of the typical signs of pulmonary hypertension
      derived from non-invasive investigations do not appear in acute pulmonary
      hypertension.

PMID- 8134806
TI  - [Treatment of acute pulmonary hypertension caused by hypoxia--cosmetic or
      clinical benefits?].
AB  - Acute or chronic exacerbated hypoxic pulmonary hypertension (PH) is a frequent
      event in patients with severe respiratory failure, such as those presenting with
      acute exacerbation of chronic obstructive pulmonary disease (COPD) or with adult
      respiratory distress syndrome (ARDS). The increased pulmonary vascular tone may
      reduce right ventricular performance. This, in turn, may trigger a drop in
      cardiac output and in oxygen delivery; furthermore, in patients with ARDS,
      increased hypoxic vasoconstriction may enhance extravascular water accumulation.
      However, the increased pulmonary vascular tone acts as a natural defence
      mechanism on the level of the air-blood barrier and may reduce the intrapulmonary
      VA/Q mismatch. Systemic vasodilators may induce favourable hemodynamic effects in
      patients with a hypoxic PH and a reduced right ventricular performance. On the
      other hand, they may worsen gas exchange through a flow-diversion phenomenon
      (from normal lung units to units with a very low VA/Q relationship) or through
      inhibition of hypoxic vasoconstriction if PvO2 increases. Recently, nitric oxide
      (NO) has been recognized as an important endothelial factor with potent
      vasorelaxing properties; preliminary studies in patients with ARDS and in those
      with severe primary pulmonary hypertension have corroborated the power of this
      molecule in improving gas exchange and pulmonary hemodynamics without deleterious
      effects on the systemic circulation. However, further randomized controlled
      studies with NO are urgently needed in order to investigate the risk-benefit
      ratio and the prognostic significance of this promising new treatment. Until this
      occurs, patients with a hypoxic acute or chronic exacerbated PH should not be
      treated according to fixed criteria but on a reasonable case by case basis.

PMID- 8134807
TI  - [The oxygen pathway: how well-built is the respiratory system?].
AB  - The question is explored of how the structural systems that constitute the
      pathway for oxygen from the air through the lung and the circulation of blood to
      the mitochondria in muscle cells affect the O2 flow rate, and whether their
      quantitative structural characteristics conform to the hypothesis of symmorphosis
      which postulates a match of structural design to overall functional demand. By
      combining physiological and morphometric studies, it is first demonstrated that
      the diffusing capacity of the human lung is slightly larger than that needed for
      maximal O2 uptake. Comparative studies of small and large species (from the mouse
      to the cow) and of athletic and sedentary species pairs (such as horses and cows)
      show that the design parameters of muscle cells and their mitochondria, of the
      capillaries, and of blood and circulation are coadjusted to O2 demand by the
      muscles during exercise. In contrast, the lung is only partially adjusted to this
      level of demand, a fact which may be related to the slight excess capacity of its
      gas exchanger. In the organ that forms the interface to the environment this may
      be a desirable safety factor.

PMID- 8134808
TI  - [Aortic valve stenosis in the old age: clinical and echocardiographic aspects].
AB  - Among 380 consecutive patients > 70 years of age, patients with a systolic heart
      murmur were investigated both clinically and by doppler echocardiography. The aim
      of the study was to compare the validity of the clinical diagnosis of valvular
      aortic stenosis in elderly patients with the results of doppler echocardiography.
      138/380 patients (36%) had a systolic heart murmur. 130 were investigated by
      doppler echocardiography. 23/130 patients with systolic murmur (18%) had moderate
      or severe aortic stenosis. Clinically, patients with moderate or severe aortic
      stenosis had a pulsus parvus et tardus of the carotid artery more often than
      patients with only slight or no evidence of aortic stenosis (61% vs 16%; p <
      0.0001). In patients with moderate or severe aortic stenosis, the murmur radiated
      more often to the carotid vessels (65% vs 19%; p < 0.0001). Systolic blood
      pressures and pressure amplitudes were lower in patients with moderate or severe
      aortic stenosis (132 vs 141 mm Hg; p < 0.01; 61 vs 68 mm Hg; p < 0.001).
      Electrocardiography showed left ventricular hypertrophy or bundle branch block
      more often in patients with moderate or severe aortic stenosis (57% vs 15%; p <
      0.01). We conclude that moderate or severe aortic stenosis is a frequent finding
      in elderly patients. Diagnosis by clinical examination may be difficult. For this
      reason, doppler echocardiography should be performed, especially when therapeutic
      consequences are to be expected from the diagnosis, such as aortic valve
      replacement or vasodilator treatment in the case of congestive heart failure.

PMID- 8134810
TI  - [Socioeconomic assessment of therapies--report of a methodological procedure].
AB  - In most cases, evaluations of treatments are restricted mainly to their clinical
      efficacy. With health resources becoming scarcer, cost-benefit-analyses assume
      greater significance in the assessment of therapies. The following article
      introduces a methodological concept for the assessment of costs and benefits in
      the treatment of mental deterioration. In this concept, data on clinical
      effectiveness were derived from an existing clinical long term trial. In
      addition, according to the characteristics of the patients included in the
      clinical trial, a new sample of similar patients was examined. A cross-sectional
      analysis was performed in order to measure resource utilization. The clinical
      trial and the cross-sectional analysis were then combined to assess the cost
      effectiveness of the treatment. For this purpose, the patients of both the
      clinical trial and the cross-sectional analysis were classified into groups
      according to severity of symptoms. The proportions of medically- and placebo
      treated patients in the different severity groups were followed up during the
      long term trial. The costs of resource utilization of each severity group were
      calculated. Consequently, depending on the course of the illness, direct
      treatment costs for medical- and placebo-treated patients could be compared. The
      results show clear differences. Rehabilitation measures and emotional care are
      provided mainly for patients with moderate symptoms, whereas the services for
      patients with more severe symptoms concentrate on basic care, such as dressing
      and undressing, washing, feeding, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134809
TI  - [Enterocolitis due to a saponin-containing drug. Apropos of a case].
AB  - The case of a 60-year-old female patient with watery diarrhea is reported. The
      history was characterized by prolonged diagnostic vagaries, due in part to
      histological features of ileal, rectal and duodenal biopsies which were
      suggestive of celiac disease. This was clinically excluded. After halting the
      intake of a compound drug containing saponins, administered for venous
      insufficiency, the diarrhea ceased immediately but could be provoked by
      rechallenge with the same drug. The patient thus had drug induced chronic
      diarrhea mimicking celiac disease, a condition which is less rare than is thought
      and easily diagnosed by a thorough enquiry on drug intake.

PMID- 8134811
TI  - [Acute erosion of the esophagus, stomach and duodenum].
AB  - Acute burns of the oesophago-gastro-duodenal tract require an immediate
      diagnostic and therapeutic approach. Early endoscopy has been shown to assist
      greatly in determining the further treatment of corrosive injury. The main task
      of radiology is to detect perforations. While first degree burns cause hardly any
      therapeutic problems, second and third degree burns require intensive care right
      from the start. Later, possible stricture formation warrants chief attention.
      Early corticosteroid treatment seems to be effective in preventing stricture
      development in second degree burns.

PMID- 8134812
TI  - [FDI: quo vadis? Federation Dentaire Internationale].

PMID- 8134813
TI  - [The dentin bonding of selected adhesive cement systems].
AB  - This in vitro study reports shear bond strengths of two dentin bonding agents
      (DBA's) with various composite luting resins. For a better imitation of the
      surface of vital human dentin, all materials were tested with dentin under
      intrapulpal pressure (19.6 cm/36 cm H2O) and exposed to thermal cycling (x 1500,
      5 degrees C/55 degrees C). For all testing groups the bonding agent and the
      composite resin were light cured at the same time. In the group of AllBond2 the
      combination with Dual Cement resulted in slightly better bond strength than with
      the other luting resins. In the group of A.R.T. Bond none of the combinations
      achieved the expected results.

PMID- 8134814
TI  - [An empirical report on fissure sealing in private practice with a duration of up
      to 10 years].
AB  - This study reports a follow-up on 2415 occlusal sealings performed in a dental
      office. After nine to ten years service time, the survival rate of all sealed
      surfaces dropped to 69.5% because of either occlusal or interproximal carious
      activities. Retention of the sealings was intact in 91.5% after one year, but
      dropped to 58.2% after nine years. In the control group 49.3% of the grooves
      showed either caries or fillings during the last check-up whereas this occurred
      in only 7.3% of the sealed teeth (ratio 7:1). The difference among those two
      groups was even bigger (45.7% vs. 5%, ratio 9:1) when excluding all two-sided
      fillings. The costs of restoring one tooth surface in the control group was on
      average two to three times higher than for the sealings group. There is no doubt
      about the beneficial prophylactic effect of the use of sealants, even in the
      context of the private dental office, and no inconvenient side-effects have been
      found. The results concerning the retention rate of sealing in this study from a
      private dental office are comparable with the average of those reported in many
      papers from U.S. Dental Schools, they are even slightly better for the caries
      incidence.

PMID- 8134815
TI  - [A new method for 3-dimensional wear measurement].
AB  - This study described a custom-made three-coordinate measuring system. It was
      based on a mechanical digital measuring device, a measuring and overlapping
      software and special specimen holders. The x-/y-measuring area was 100,000 x
      100,000 microns and the vertical measuring range was 30,000 microns. The
      measurements were reproducible within the resolution of 1.0 microns over the
      entire measuring range. The maximum measurable tilt relative to the horizontal
      plane was < 59 degrees. The total accuracy of the system, which was influenced by
      the resolution of the measuring device, the reproducibility of the measurements,
      the accuracy of the test sample reposition and the measuring/overlapping software
      was better than 1.0 microns. For the graphic presentation of the data commercial
      software was adopted. Its capabilities were demonstrated on selected examples.
      The measuring system is an efficient device, which is extremely well adopted to
      the problem of quantitative wear measurement in dentistry.

PMID- 8134816
TI  - [Apical root resection. Retrograde cavity preparation and retrograde root canal
      filling materials].

PMID- 8134817
TI  - [Functional disorders of the masticatory apparatus. A report on the education
      course at Aarburg, 6 November 1993].

PMID- 8134818
TI  - [Orthognathic surgery and dental office hygiene. A report of the annual meeting
      of the Swiss Society of Orthodontics].

PMID- 8134819
TI  - [No solution without Europe. The Swiss dentist in the European economic
      framework].

PMID- 8134820
TI  - [Oral health: self-care and dental care: strategies for the patient and the
      practice. A continuing education course of the Division for Preventive Dentistry,
      Periodontology and Cariology, the Dentistry Institute of the University of Zurich
      in cooperation with the Clinic for Periodontology and Dental Bridgework, the
      Dental Clinics of the University of Bern and the Study Club ARP of 29 and 30
      October 1993 in Zurich-Regensdorf: A factual summary].

PMID- 8134821
TI  - Inside story.

PMID- 8134822
TI  - Biocatalysts turn rings around the competition.

PMID- 8134823
TI  - Prosthetic vision. Workers resume the quest for a seeing-eye device.

PMID- 8134824
TI  - Molecular mischief. Spectroscopic studies may point to a cause of schizophrenia.

PMID- 8134825
TI  - Gene rich, cash poor. The genome project has plenty of findings but not dollars.

PMID- 8134826
TI  - Can the growing human population feed itself?

PMID- 8134827
TI  - Targeted gene replacement.

PMID- 8134828
TI  - Renovating Italian science.

PMID- 8134829
TI  - National Institutes of Health. Report calls for smaller clinical center.

PMID- 8134830
TI  - Breast cancer. How not to publicize a misconduct finding.

PMID- 8134831
TI  - Mummy settles TB antiquity debate.

PMID- 8134832
TI  - New HIV group baffles French test.

PMID- 8134833
TI  - Materials science.

PMID- 8134834
TI  - Functional polymers and dendrimers: reactivity, molecular architecture, and
      interfacial energy.
AB  - The interaction of polymers with their environment depends largely on the
      functional groups they carry. Interfaces between different polymers or between
      polymers and other surfaces can be strengthened through the design of molecular
      interactions such as hydrogen bonding and through the control of polymer
      architecture. The placement of functional groups at polymer chain ends or in well
      defined segments can determine the ultimate properties. Three-dimensional
      synthetic polymers such as dendrimers can be fashioned to encapsulate reactive
      sites or provide highly controlled surfaces and interfaces.

PMID- 8134835
TI  - New challenges in biomaterials.
AB  - Significant opportunities and challenges exist in the creation and
      characterization of biomaterials. Materials have been designed for contact with
      blood, as replacements for soft and hard tissues, as adhesives, and as dental
      materials. Current methods of synthesis and characterization of these materials
      are outlined. Approaches for controlling the interface between tissue and
      biomaterials and ways in which the engineered materials may contribute to
      medicine are considered.

PMID- 8134836
TI  - Langmuir-Blodgett films.
AB  - The controlled transfer of organized monolayers of amphiphilic molecules from the
      airwater interface to a solid substrate was the first molecular-scale technology
      for the creation of new materials. However, the potential benefits of the
      technology envisioned by Langmuir and Blodgett in the 1930s have yet to be fully
      realized. Problems of reproducibility and defects and the lack of basic
      understanding of the packing of complex molecules in thin films have continued to
      thwart practical applications of Langmuir-Blodgett films and devices made from
      such films. However, modern high-resolution x-ray diffraction and scanning probe
      microscopy have proven to be ideal tools to resolve many of the basic questions
      involving thin organic films. Here, studies are presented of molecular order and
      organization in thin films of fatty acid salts, the prototypical system of
      Katharine Blodgett. Even these relatively simple systems present liquid, hexatic,
      and crystalline order; van der Waals and strained layer epitaxy on various
      substrates; wide variations in crystal symmetry and interfacial area with
      counterions; modulated superstructures; and coexisting lattice structures. The
      wide variety of possible structures presents both a challenge and an opportunity
      for future molecular design of organic thin-film devices.

PMID- 8134837
TI  - The Drosophila saxophone gene: a serine-threonine kinase receptor of the TGF-beta
      superfamily.
AB  - The Drosophila decapentaplegic (dpp) gene encodes a transforming growth factor
      beta (TGF-beta)-like protein that plays a key role in several aspects of
      development. Transduction of the DPP signal was investigated by cloning of serine
      threonine kinase transmembrane receptors from Drosophila because this type of
      receptor is specific for the TGF-beta-like ligands. Here evidence is provided
      demonstrating that the Drosophila saxophone (sax) gene, a previously identified
      female sterile locus, encodes a TGF-beta-like type I receptor. Embryos from sax
      mothers and dpp embryos exhibit similar mutant phenotypes during early
      gastrulation, and these two loci exhibit genetic interactions, which suggest that
      they are utilized in the same pathway. These data suggest that sax encodes a
      receptor for dpp.

PMID- 8134838
TI  - High-resolution solution structure of the beta chemokine hMIP-1 beta by
      multidimensional NMR.
AB  - The three-dimensional structure of a member of the beta subfamily of chemokines,
      human macrophage inflammatory protein-1 beta (hMIP-1 beta), has been determined
      with the use of solution multidimensional heteronuclear magnetic resonance
      spectroscopy. Human MIP-1 beta is a symmetric homodimer with a relative molecular
      mass of approximately 16 kilodaltons. The structure of the hMIP-1 beta monomer is
      similar to that of the related alpha chemokine interleukin-8 (IL-8). However, the
      quaternary structures of the two proteins are entirely distinct, and the dimer
      interface is formed by a completely different set of residues. Whereas the IL-8
      dimer is globular, the hMIP-1 beta dimer is elongated and cylindrical. This
      provides a rational explanation for the absence of cross-binding and reactivity
      between the alpha and beta chemokine subfamilies. Calculation of the solvation
      free energies of dimerization suggests that the formation and stabilization of
      the two different types of dimers arise from the burial of hydrophobic residues.

PMID- 8134839
TI  - Direct signaling from astrocytes to neurons in cultures of mammalian brain cells.
AB  - Although astrocytes have been considered to be supportive, rather than
      transmissive, in the adult nervous system, recent studies have challenged this
      assumption by demonstrating that astrocytes possess functional neurotransmitter
      receptors. Astrocytes are now shown to directly modulate the free cytosolic
      calcium, and hence transmission characteristics, of neighboring neurons. When a
      focal electric field potential was applied to single astrocytes in mixed cultures
      of rat forebrain astrocytes and neurons, a prompt elevation of calcium occurred
      in the target cell. This in turn triggered a wave of calcium increase, which
      propagated from astrocyte to astrocyte. Neurons resting on these astrocytes
      responded with large increases in their concentration of cytosolic calcium. The
      gap junction blocker octanol attenuated the neuronal response, which suggests
      that the astrocytic-neuronal signaling is mediated through intercellular
      connections rather than synaptically. This neuronal response to local astrocytic
      stimulation may mediate local intercellular communication within the brain.

PMID- 8134840
TI  - Genetic mapping of quantitative trait loci for growth and fatness in pigs.
AB  - The European wild boar was crossed with the domesticated Large White pig to
      genetically dissect phenotypic differences between these populations for growth
      and fat deposition. The most important effects were clustered on chromosome 4,
      with a single region accounting for a large part of the breed difference in
      growth rate, fatness, and length of the small intestine. The study is an advance
      in genome analyses and documents the usefulness of crosses between divergent
      outbred populations for the detection and characterization of quantitative trait
      loci. The genetic mapping of a major locus for fat deposition in the pig could
      have implications for understanding human obesity.

PMID- 8134841
TI  - [Methods of the assessment of the quality of hospital nursing care. The child in
      respiratory difficulty].

PMID- 8134842
TI  - [Preparing the patient for tube feeding at home].

PMID- 8134843
TI  - [Ethics and drug dependence].

PMID- 8134844
TI  - [Sound and efficient leadership].

PMID- 8134845
TI  - [The prevention of femoral neck fractures in the elderly woman with vitamin D and
      calcium].

PMID- 8134846
TI  - [Drugs: a challenge for volunteers].

PMID- 8134847
TI  - [The order of nurses].

PMID- 8134848
TI  - Hematocrit and bleeding time: an update.
AB  - The bleeding time is prolonged in anemic patients independent of their platelet
      count and is shortened by elevating the hematocrit. It is theorized that an
      increase in circulating red blood cells increases platelet radial movement and
      interaction with endothelium. Platelet dysfunction in uremia is well known but
      poorly understood. Anemia is one contributory factor; others may involve storage
      pool deficiency, increased vessel wall prostaglandin production, and abnormal
      platelet arachidonic acid metabolism. Ameliorating anemia with red blood cell
      transfusions has been shown to shorten the bleeding time without affecting other
      platelet function values. Recently, recombinant human erythropoietin has been
      shown to shorten the bleeding time, with a parallel rise in hematocrit level to
      30%. Clinicians should be aware that a diminished hematocrit may contribute to
      the bleeding tendency already present in patients with thrombocytopenia.

PMID- 8134849
TI  - Attention deficit hyperactivity disorder in adults: diagnosis, treatment, and
      prognosis.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common, disabling disease in
      adults. Newly developed diagnostic measures are available to screen for and
      support the diagnosis. ADHD typically causes complaints of disturbances of
      attention, impulsivity, and hyperactivity, although a subgroup of patients have
      only problems with attention. The disorder may be subtle or it may be obscured by
      secondary problems; the boundaries of the syndrome often blur with those of other
      disease entities. Once the diagnosis is confirmed, effective pharmacologic
      treatments are available. Psychologic treatment serves an important adjunctive
      role for associated problems and concurrent psychologic disorders. Marked
      improvement in quality of life often occurs after diagnosis and appropriate
      treatment.

PMID- 8134850
TI  - Pharmacologic management of obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is an intriguing, difficult problem
      characterized by anxiety-producing intrusive thoughts and performance of anxiety
      reducing rituals. Current evidence suggests that OCD may be associated with
      dysregulation of serotonin and dopamine neurotransmission. Numerous early studies
      involving the serotonin-specific reuptake inhibitor clomipramine led to the
      formulation of this hypothesis. Positive results with clomipramine initiated
      further research with other serotonin-specific reuptake inhibitors, such as
      fluoxetine, fluvoxamine, sertraline, and serotonergic agents such as buspirone
      and trazodone. Findings from a number of clinical trials suggest that drugs that
      inhibit serotonin reuptake or affect serotonergic transmission in other ways are
      of clear benefit in the treatment of OCD. These drugs may be more effective for
      obsessive thoughts than for compulsive rituals. Effective pharmacotherapy can
      dramatically decrease obsessive-compulsive symptoms and improve the patient's
      quality of life.

PMID- 8134851
TI  - Changes in smoking behavior and body weight after implementation of a no-smoking
      policy in the workplace.
AB  - There is little information on the long-term consequences for employees when no
      smoking policies are established in the workplace. Our study was designed to
      assess changes in employee health and smoking behavior. Of the original 60
      subjects, 40 employees (18 smokers, 22 nonsmokers) completed this study, which
      was conducted in a major medical institution. Nonsmokers were recruited as part
      of the study to determine whether they showed evidence of workplace carbon
      monoxide associated with passive smoke, potentially inhaled at the work site.
      Baseline measurements of smoking frequency, carbon monoxide, and weight were
      obtained during the month preceding the smoking restrictions and at 6 and 18
      months afterward. Smokers made significant reductions in daily smoking during the
      first 6 months but gradually returned to prepolicy levels over the following
      year. Smokers, in particular, showed increases in weight. Smokers gained 4.93 lb
      after 18 months, whereas nonsmokers gained 2.25 lb in the same period. Nonsmoker
      employees showed no evidence of workplace carbon monoxide exposure associated
      with passive smoke. We discuss the implications of the findings for no-smoking
      policies in the workplace.

PMID- 8134852
TI  - Carpal tunnel syndrome: classic clinical symptoms and electrodiagnostic studies
      in poultry workers with hand, wrist, and forearm pain.
AB  - Carpal tunnel syndrome (CTS) has been linked to repetitive motion only in the
      past 15 years or so. Often the studies supporting this proposed link have not
      used strict clinical criteria and have rarely had electrodiagnostic confirmation
      of the diagnosis. In order to better assess the actual incidence of CTS in
      patients in a repetitive-motion job who had pain, numbness, tingling, or all
      three in the hand, wrist, or forearm, we examined 112 consecutive charts of such
      patients referred to a consulting neurologist for a possible diagnosis of carpal
      tunnel syndrome. Thirty-five percent of those patients had either classic
      clinical symptoms or positive electrodiagnostic results, but only half of these
      (17% of the total) actually had both. It is thus suggested that the incidence of
      CTS in patients doing repetitive motion may have been overestimated in the
      literature, and very strict clinical and electrodiagnostic criteria should be
      used before a diagnosis of carpal tunnel syndrome is made or surgery is
      contemplated in these patients.

PMID- 8134853
TI  - Intelligibility of tracheoesophageal speech among naive listeners.
AB  - Tracheoesophageal (TE) speech is now the most common method of voice
      rehabilitation after total laryngectomy. The speech intelligibility of
      laryngectomees who use TE speech as their primary mode of communication was
      evaluated by 20 "naive" listeners. Two speech intelligibility tests were
      administered using phonetically balanced rhyming words or lists of spondee words.
      The overall intelligibility for the group of laryngectomees was 76%, with a wide
      range of variability among the individual TE speakers. We concluded that TE
      speech is significantly less intelligible to naive listeners than normal
      laryngeal speech; further refinement of voice rehabilitation for laryngectomees
      is needed.

PMID- 8134854
TI  - Use of technetium Tc 99m sestamibi and iodine 123 radionuclide scan for
      preoperative localization of abnormal parathyroid glands in primary
      hyperparathyroidism.
AB  - The imaging methods currently used to localize the parathyroid gland in patients
      with hyperparathyroidism have been criticized as unreliable and even misleading.
      We evaluated a new imaging technique that uses technetium Tc 99m sestamibi and
      iodine 123. We studied 21 patients having a diagnosis of primary
      hyperparathyroidism and no previous parathyroid surgery. Scintigraphy to localize
      the abnormal parathyroid was done before operation. A solitary adenoma was
      localized in 14 patients. Six patients had images consistent with diffuse
      hyperplasia, and one patient had a dual adenoma. The surgical and histologic
      findings confirmed the preoperative data. The sensitivity of this method is
      87.5%, the specificity is 100%, and the predictive value is 100%. This new method
      of preoperative localization of abnormal parathyroid glands is useful in patients
      having initial neck exploration for primary hyperparathyroidism.

PMID- 8134855
TI  - Sellar emptiness on routine magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) has provided a clear view of the sella turcica
      and the pituitary gland, even on "routine" procedures that invariably include the
      sagittal T1-weighted sequence. A pituitary gland that does not fully occupy the
      sella is a common observation, even in normal individuals. Terms such as "empty
      sella" and "partially empty sella" have become more commonly used, occasionally
      giving rise to some confusion regarding their clinical significance. In a
      prospective study of 50 "near-normal" patients, based exclusively on the
      midsagittal T1-weighted image, we have found a statistically significant increase
      in sellar emptiness with age, a phenomenon that is more prominent in women. The
      finding of an empty or partially empty sella on routine MRI of the brain is
      therefore usually of no clinical significance.

PMID- 8134856
TI  - Comparison of individuals receiving anonymous and confidential testing for HIV.
AB  - We assessed the magnitude, demographics, seroprevalence, and reasons for site
      selection among South Carolina residents who chose to be tested in bordering
      states offering anonymous testing for human immunodeficiency virus (HIV).
      Residents tested from July 1990 through July 1991 at selected HIV testing sites
      in bordering states were surveyed and HIV test results were recorded. Of the 75
      residents tested at these sites, 66 (88%) were white, 44 (59%) were male, and 9
      (12.3%) of the 73 whose test results were recorded were HIV infected. During the
      same period, 57,137 individuals were HIV tested in-state by the state health
      department, of which 1,752 (3.1%) were positive. Residents tested outside the
      state were more likely to be HIV infected, male, and white than individuals
      tested within the state. Our findings suggest that although large numbers of
      South Carolinians are not HIV tested anonymously in other states, those tested
      anonymously out of state have a different demographic and risk profile than those
      tested confidentially in state.

PMID- 8134857
TI  - Relationship between serum cyclo(His-Pro) concentrations and the nutritional
      status of HIV-infected patients.
AB  - Cyclo(His-Pro) (CHP) is a gut-neuropeptide that influences both appetite and
      carbohydrate metabolism. This study was undertaken to determine whether
      concentrations of CHP correlated with various clinical markers of nutritional
      status and progression of HIV infection. Serum concentrations of CHP were
      analyzed in a clinical sample of 100 HIV-positive patients whose HIV clinical
      status ranged from asymptomatic to advanced disease with weight loss. We found a
      relationship between CHP concentrations and serum albumin and hemoglobin levels,
      markers of chronic nutrition and disease. However, no correlation was seen
      between CHP and cortisol concentrations, a marker of acute stress. To analyze the
      relationship of HIV clinical stage and CHP, patients were divided into three
      subgroups: asymptomatic, mildly symptomatic, and clear-cut AIDS. CHP
      concentrations were significantly correlated with HIV clinical stage. These data
      lead to the hypothesis that CHP is a marker of disease progression and that it
      potentially plays a role in modulating the nutrition of HIV-infected patients.

PMID- 8134858
TI  - Crusted (Norwegian) scabies in patients with AIDS: the range of clinical
      presentations.
AB  - Crusted (Norwegian) scabies in AIDS patients can be manifested in both typical
      and atypical forms. Although the classic, hyperkeratotic, nonpruritic lesions are
      most common, reported cases have ranged in spectrum from crusting with pruritus
      to a pruritic, papular dermatitis to those resembling Darier's disease or
      psoriasis. We report two additional cases of crusted scabies in AIDS patients,
      one with typical crusted, hyperkeratotic though pruritic lesions and one with
      severe pruritus and rare papules, initially misdiagnosed as "pruritus of AIDS."
      Because of the extremely contagious nature of crusted scabies, as well as its
      potential for complete cure with appropriate therapy, a high degree of suspicion
      for this disorder should be maintained in AIDS patients, even when the lesions do
      not have the classical appearance. The discovery of crusted scabies, whether in
      its common or its atypical form should prompt testing for the human
      immunodeficiency virus (HIV).

PMID- 8134859
TI  - HIV and pulmonary hypertension: a review.
AB  - We describe two unique cases of pulmonary hypertension in association with the
      human immunodeficiency virus (HIV) and review the 28 previously reported cases in
      the world literature. Our first patient has coexistent chronic active hepatitis,
      which has previously been associated with the development of plexogenic pulmonary
      hypertension; however, our second case clearly demonstrates a closer link between
      HIV infection and pulmonary hypertension. Unlike previously reported cases, our
      latter case was devoid of all other coexistent factors including intravenous drug
      abuse, hepatitis B antigenemia, coexisting immunologic lung parenchymal injury,
      and hepatitis. Additionally, this is the first case documenting the presence of
      asymptomatic type II cryoglobulins in an HIV-positive patient with plexogenic
      pulmonary hypertension.

PMID- 8134860
TI  - Loop ileostomy: a reliable method of diversion.
AB  - Between September 1983 and March 1989, 36 loop ileostomies were performed on 34
      patients (16 male and 18 female, mean age 36 years, range 11 to 68). Thirty-two
      patients had ileoanal pouch procedures (30 for ulcerative colitis and two for
      familial polyposis). One patient had a low anterior resection and another had a
      coloanal procedure. By the time of this review, 31 of the loop ileostomies were
      closed. The average time before closure was 5 months and the average length of
      follow-up was 37 months. All stomas were brought out through the rectus muscle in
      the right side of the abdomen, without ileal rotation, mesenteric fixation, or
      parastomal fascial sutures. A support rod was left in place for 3 to 4 weeks
      postoperatively. There were no major difficulties with skin irritation or
      appliance management and no instance of parastomal abscess and stoma retraction.
      Although no complications related to the ostomy or its closure were encountered
      in these patients, small bowel obstruction before closure (8 patients) or after
      takedown (5 patients) of the loop ileostomy required operative correction in one
      patient in each group.

PMID- 8134861
TI  - Cervical carcinoma in women less than 35 years of age.
AB  - We retrospectively studied 80 patients, less than 35 years old, who were being
      treated for invasive cervical carcinoma at Charity Hospital of Louisiana in New
      Orleans. The period covered by the study was March 1980 to November 1989. The
      study group represented 9.3% (80/862) of the total patients seen with the
      disease. Disease stage was IB in 50 patients, IIA in 4, IIB in 14, IIIA in 5,
      IIIB in 6, and IVA in 1 patient. Histopathologic classes included 74 squamous
      cell carcinomas, 3 adenosquamous carcinomas, 2 adenocarcinomas, and 1 anaplastic
      carcinoma. Treatment used was either radical hysterectomy, irradiation alone, or
      irradiation followed by hysterectomy. Five-year actuarial survival rates were as
      follows: stage IB, 81.6%; stage IIA, 25.0%; stage IIB, 29.8%; stage IIIA, 20.0%;
      and stage IIIB, 33.4%. The only patient with stage IV cancer died of disease. Our
      findings do not reveal a relationship between age and survival in stage IB
      carcinoma of the cervix, and the numbers in the other stages are too small to
      comment on.

PMID- 8134862
TI  - Functioning adrenal cortical carcinoma in pregnancy.
AB  - Functioning adrenal cortical carcinoma occurring concurrently with pregnancy is
      rare. Only four cases have been reported previously in the world literature. Here
      I discuss two additional cases of functioning adrenal cortical carcinoma in
      pregnancy. Both patients died of the illness. Despite the use of surgery and
      chemotherapy, the prognosis remains grim. Fetal prognosis, however, is excellent.

PMID- 8134863
TI  - Development of a geropsychiatric unit.
AB  - Acute services to older citizens often require health care professionals to
      manage problems that are difficult to assess and treat. Age-related complications
      such as physical decline and the presence of psychiatric and medical illness
      together can produce an array of confusing symptoms for the physician. This study
      examines the diagnostic outcomes of the first 100 patients admitted to an acute
      care-based geropsychiatric unit. Assessment protocols and treatment interventions
      are described and results of patient progress are discussed.

PMID- 8134864
TI  - Paroxysmal cold hemoglobinuria associated with non-Hodgkin's lymphoma.
AB  - This report describes a patient with severe unexplained recurrent hemolytic
      anemia and congestive heart failure. Donath-Landsteiner antibodies, suggestive of
      paroxysmal cold hemoglobinuria (PCH), were detected. On postmortem examination, a
      diagnosis of non-Hodgkin's lymphoma, primarily involving the heart, was made.
      This previously undescribed association expands on the clinical and serologic
      spectrum of non-Hodgkin's lymphoma and PCH. Unexplained hemolytic anemia in the
      elderly should raise the suspicion of an underlying lymphoproliferative disorder.

PMID- 8134865
TI  - Postoperative hyperthermia in a patient having cortical brain resection.
AB  - When a profound fever occurs in a surgical patient, clinicians usually start
      thinking about the malignant hyperthermia syndrome. Simple consideration of the
      clinical situation, the patient's medical history, and a few rapid laboratory
      assessments are enough to direct appropriate treatment.

PMID- 8134866
TI  - Occult wrist pain due to capitate nonunion.
AB  - Capitate nonunion is an uncommon cause of occult wrist pain. History of wrist
      injury, tenderness in the distal carpal row, capitate-view x-rays, and special
      radiographic studies such as bone scan, CT scan, or magnetic resonance imaging
      can confirm the diagnosis.

PMID- 8134867
TI  - Reversible cystic dilatation of distal airways due to foreign body.
AB  - We describe a child with foreign body aspiration whose chest radiograph showed an
      unusual appearance of multiple round lucencies simulating bronchiectasis. This
      appearance is contrary to the usual appearance of emphysema due to the check
      valve type of obstruction. This report is particularly useful for pediatricians
      and family physicians, who should be aware of the variable appearances of foreign
      body aspiration. Our case emphasizes the necessity of early bronchoscopy in
      pediatric patients with unresolving pneumonia.

PMID- 8134868
TI  - Hereditary warfarin resistance.
AB  - We report on a case of hereditary warfarin resistance in a 27-year-old black man.
      Hereditary warfarin resistance is a rare disorder transmitted as autosomal
      dominant. It should be suspected in patients who require high doses of warfarin,
      achieve high plasma warfarin levels, and have a normal plasma warfarin clearance.
      Treatment includes either high dose warfarin or heparin (subcutaneous).

PMID- 8134869
TI  - Dexamethasone-induced tumor lysis syndrome in high-grade non-Hodgkin's lymphoma.
AB  - Tumor lysis syndrome is a catastrophic complication of the treatment of certain
      neoplasms. It most commonly occurs in association with hematologic malignancies
      and manifests a few hours to a few days after initiation of specific
      chemotherapy. It has rarely been encountered as a complication of steroid therapy
      only. Tumor lysis syndrome is a potentially fatal condition if it is not
      recognized promptly and managed aggressively. We report on a patient with high
      grade non-Hodgkin's lymphoma who developed severe metabolic acidosis,
      hyperkalemia, hyperphosphatemia, and hypocalcemia within 2 days of starting
      corticosteroid therapy. He was managed with intravenous fluids, bicarbonate
      infusion, calcium gluconate, and 25% dextrose with insulin. He did not respond to
      these measures and died within a few hours of the diagnosis of tumor lysis
      syndrome. Increasing awareness of this complication and proper prophylactic
      measures are necessary to improve the outcome.

PMID- 8134871
TI  - Carbon dioxide embolism during laparoscopic cholecystectomy.
AB  - We present a 38-year-old woman with cholelithiasis having laparoscopic
      cholecystectomy. After two attempts of abdominal insufflation using CO2 and a
      Verres needle, the patient had symptoms consistent with a venous gas embolism.
      The patient was treated quickly and recovered without sequelae. Surgery was
      continued, and inspection of the liver showed two Verres needle puncture wounds.

PMID- 8134870
TI  - Transient diabetes insipidus following electrical burns in two patients.
AB  - We report on two healthy white men who sustained high-voltage electrical burns
      and were transferred to our regional burn center for specialized care. Within 24
      hours of admission, both patients developed clinical signs and laboratory
      evidence of diabetes insipidus. With appropriate treatment, no sequelae occurred
      and their endocrinopathy spontaneously resolved. Diabetes insipidus following
      traumatic events is not uncommon; however, it has never been reported following
      an electrical injury.

PMID- 8134872
TI  - Complications after subfascial carpal tunnel release.
AB  - The two cases we report reiterate the dangers of performing a carpal tunnel
      release through a small transverse or longitudinal incision at the wrist crease.
      We concur with other authors that this method of carpal tunnel release has an
      unacceptably high complication rate, and its potential risks do not justify its
      use.

PMID- 8134873
TI  - Predicting severity of trauma.

PMID- 8134874
TI  - Diagnosis of myocardial contusion.

PMID- 8134875
TI  - Can environmental factors explain the epidemiology of schizophrenia in immigrant
      groups?
AB  - Recent evidence suggests that high rates of schizophrenia in first- and second
      generation immigrants could be due to exposure to environmental factors such as
      viral infections in the host country. These findings are discussed alongside
      parallel data relating to other diseases such as multiple sclerosis and diabetes
      mellitus. It is argued that in each case the interaction between the
      environmental agent and constitutional factors related to the immune system need
      to be considered.

PMID- 8134876
TI  - Characteristics of hospital-treated schizophrenia in Sao Paulo, Brazil.
AB  - This paper reports a study on the prevalence of hospital-treated schizophrenia in
      a large urban centre in Brazil. A sample of 124 individuals from a defined
      catchment area of Sao Paulo consecutively admitted to psychiatric hospitals due
      to acute episodes of non-affective psychoses were assessed by standardized
      instruments for mental state and social adjustment. The sample was predominantly
      white (72.6%), single (65.2%), Catholic (61.3%) and not born in that city
      (58.9%). Eighty-six subjects fulfilled DSM-III-R criteria for schizophrenia
      (69.3%), 15 were classified as schizophreniform psychosis (12.1%), and 7 as
      schizoaffective (5.6%). Almost two-thirds showed Schneider's 'first rank'
      symptoms. Social adjustment before admission was poor or very poor in nearly half
      the sample. Mean age at onset was 3.2 years earlier in men than in women (P =
      0.007). No gender differences in mental state or social adjustment were observed.
      Individuals born outside Sao Paulo State had significantly more florid symptoms
      than those born in that state. These findings suggest that the features of
      schizophrenia in a large urban centre of Brazil are consistent with the patterns
      of schizophrenia described in Western developed countries.

PMID- 8134877
TI  - Language content and schizophrenia in acute phase Turkish patients.
AB  - The purpose of this study was to replicate and extend, in a Turkish sample,
      previous investigations of speech content in English-speaking schizophrenics.
      Computer content analytic procedures, which quantify thematic emphases in the
      subjects' free speech, have been shown to differentiate schizophrenic patients
      from other acutely ill psychiatric patients and from normal controls. We repeated
      the speech sampling procedure with hospitalized psychiatric patients in Turkey,
      and analyzed their responses using content analysis procedures with a translation
      of the dictionary or language classification system used in the original studies
      of English-speaking patients in the United States. Eighty subjects were included
      in the study: 20 schizophrenics, 20 depressives, 20 manics and 20 healthy
      controls. There were ten females and ten males in each group. After being
      diagnosed separately by two clinicians using the Turkish version of the
      Structured Clinical Interview for DSM-III-R (SCID), each subject's free speech
      was tape-recorded in a standardized session. The speech content of Turkish
      patients with schizophrenia exhibited considerable similarity to that previously
      observed in American subjects, but there were certain dissimilarities that
      appeared to reflect the impact of culture on the manifestations of the
      schizophrenic disorder. The phenomenological differences between the three
      psychiatric syndromes compared were also reflected in the results of the content
      analysis. The most dissimilar syndromes were mania and depression whereas the
      most similar were mania and schizophrenia. The particular word categories
      emphasized by specific groups also appeared to be consistent with the effects of
      their psychiatric disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134878
TI  - The incidence of mania in two areas in the United Kingdom.
AB  - The incidence of mania in an inner-city area was estimated by both a casenote
      search with later interview and a prospective interview method. The incidence was
      found to be twice as high as that in a more rural area, as estimated by the
      casenote-based method. Though a high proportion of the inner-city population were
      from ethnic minorities, particularly Afro-Caribbean, this could not explain the
      discrepancy. It is suggested that the incidence of mania is related to the
      mobility of the local population.

PMID- 8134879
TI  - Help-seeking behaviour for psychiatric disorder from physicians or psychiatrists
      in Greece.
AB  - A nationwide home survey on the identification of possible factors affecting help
      seeking behaviour for psychiatric reasons and the prevalence of related
      psychosocial problems was carried out in a sample of 3754 adults in Greece. Of
      the total of 570 respondents who reported at the personal interview that they had
      a serious mental health problem, only 40.8% reported that they had attended a
      physician or a psychiatrist. A significant proportion of this population (42.5%)
      had sought the help of a physician. Multivariate analysis revealed two opposite
      groups of factors determining help-seeking behaviour. Respondents with a serious
      psychopathological profile (suicidal, depressive and a history of
      hospitalization) tended to be under psychiatric care. Respondents of lower socio
      economic status expressing psychosomatic symptoms were usually the clientelle of
      physicians. The results are discussed in relation to the need for the development
      of strategies and techniques in reaching out to mentally ill patients by the
      appropriate specialists.

PMID- 8134880
TI  - Causal attributions for illness among Turkish psychiatric out-patients and
      differences between diagnostic groups.
AB  - Causal attributions of 152 Turkish non-psychotic psychiatric out-patients for the
      development of their psychological problems were examined by using a 31-item
      attributions for psychological problems questionnaire (APP). The factor analysis
      of the responses to the APP yielded seven factors, which were: attributions to
      conflicts within the family of origin and with the present family, attributions
      to personal-characterological and behavioural attributes, work problems,
      interpersonal conflicts and bad luck. Examination of the causal attributions of
      patients from three DSM-III-R diagnostic groups revealed no significant
      differences between diagnostic groups. The highest attributional scores were for
      conflicts with the present family and personal-characterological attributes.

PMID- 8134881
TI  - Sociogrid analysis of a child and adolescent psychiatric clinic.
AB  - The diverse roles of medical health professionals working in a child psychiatry
      clinic were examined using sociogrid analysis allowing for idiographic and
      nomothetic analyses, the latter enabling assessment of larger numbers of
      individuals. Role repertory grid analysis was further used to explore the
      cognitive structure of the doctor and the nurse. As a result, insight was offered
      regarding the configuration of the clinic organisation, with detailed evaluation
      of occupational boundaries and interaction between roles. Central figures in the
      social network were those of the physician and the parents of the patient. The
      social worker and the psychologist appeared isolated from the rest of the
      treatment group and seemed to work independently with the parents, in contrast to
      the physician who did not relate to either the parent or the patient.
      Administrators occupied a unique pivotal position between these two core
      occupational clusters (parents, social worker, patient and psychologist;
      physician, nursing and care, occupational therapist and physiotherapist).

PMID- 8134883
TI  - Lyme disease: current problems in diagnosis, therapy, and prevention.

PMID- 8134882
TI  - Alcohol-related problems within the family and global functioning of the
      children: a population-based study.
AB  - We carried out a population-based prevalence study to assess the association
      between the presence of alcohol-related problems within the family and the risk
      of disorders in the children's global functioning level. We enrolled 394 children
      attending nursery, primary and secondary schools and their parents living in two
      municipalities in Central Italy. Alcohol-related problems within the family were
      reported by registered records obtained from general practitioners and teachers,
      who were considered as preference raters. The children's level of functioning was
      assessed by teachers, who attributed to each school child a score according to
      the Children Global Assessment Scale (CGAS). The number of reports of alcohol
      related problems within the family and the CGAS scores were considered,
      respectively, as independent and dependent variables in a multiple logistic
      regression model for ordinal outcome variables. The children's sex and age, and
      the age of their parents, the duration of the parents' education and family size
      were considered as covariates. We found a strong association between a poor level
      of functioning in the children in the social environment and alcohol-related
      problems within the family. The prevalence odds ratio (and 95% confidence
      interval) decreased from 0.5 (range 0.2-1.3) for children whose families were
      reported by one rater to 0.4 (range 0.2-0.8) for children whose families were
      reported by two raters, the non-reported families being the reference category,
      suggesting that the level of functioning of the child decreased as reports of
      alcohol-related problems in the family increased.

PMID- 8134884
TI  - Total knee arthroplasty in rheumatoid arthritis.

PMID- 8134885
TI  - Surgical treatment of the hip and knee joint in juvenile rheumatoid arthritis.

PMID- 8134886
TI  - [Inflammation and destruction of joints and inhibitory factors of repair].

PMID- 8134887
TI  - [Etiology, physiopathology, and diagnosis of osteoarthritis].

PMID- 8134888
TI  - [The adjustment to lower limb functional reconstruction in chronic rheumatoid
      arthritis].

PMID- 8134889
TI  - [Causative genes in rheumatoid arthritis--recent advancement in molecular
      biology].

PMID- 8134890
TI  - Restitution of enamel after interdental stripping.
AB  - This paper studies the effect of interdental stripping on the enamel surface and
      evaluates methods to restitute the treated surface. Extracted teeth mounted in a
      semielastic material were subjected to stripping by different kinds of steel
      strips. The treated enamel surfaces were then polished in several different ways.
      The effects were studied by SEM and profilometry. It was concluded that the
      coarsest strips produced irregularities of such a magnitude that polishing had
      very limited effect. Polishing starting with coarse polishing strips followed by
      gradually finer gave the best result. An increase in number of strokes and use of
      all grades of polishing strips slightly improved the result.

PMID- 8134891
TI  - Long term clinical evaluation of conical crown retained dentures.
AB  - The conical crown was introduced by K.H. Korber more than twenty years ago, as a
      development of the well known telescopic crown. In combination with a removable
      denture, the conical crown has become widely used in Germany and Sweden, since
      the system enable modifications with maintained function if abutments are lost.
      All 78 patients treated with conical crown retained dentures, at the School of
      Dentistry, Dept. Prosthetic Dentistry, Lund University, 1983-1988, were included
      in a 40 month follow up study using the CDA quality evaluation system. More than
      80% of the removable dentures and abutments were in function at the time of
      examination. Forty-four percent of the conical crown retained dentures were
      considered having acceptable quality while 56% were not acceptable, mainly due to
      caries at the abutments margins.

PMID- 8134892
TI  - Effect of canine guidance of maxillary occlusal splint on level of activation of
      masticatory muscles.
AB  - The effect of canine guidance of a full-arch maxillary flat occlusal splint on
      the level of activation of the anterior and posterior, temporal, masseter and
      suprahyoid muscles during maximal clenching, were studied in 14 subjects without
      craniomandibular disorders. The results revealed that, the level of
      electromyographic activity of anterior and posterior temporal and suprahyoid
      muscles during maximal clenching on the occlusal splint in habitual closure was
      unchanged, as compared to biting in the intercuspal position (ICP), while the
      activity in the masseter muscle, on average, was increased slightly (13 percent).
      In contrast, the level of activation of the jaw elevator muscles decreased
      significantly during maximal clenching on the cuspid ramp of the splint, as
      compared to the biting in ICP or clenching on the splint. However, the degree of
      reduction of activity was not symmetrical, and was most pronounced in the
      masseter muscle of the biting side and in the anterior and posterior temporal
      muscles of the non-biting side. No significant difference was observed in the
      activity of the suprahyoid muscles.

PMID- 8134893
TI  - The influence of the caries definition on disease prevalence and distribution in
      20-23 year old persons in Stockholm.
AB  - The aim was to investigate to what extent an extension of the caries criterion
      into the dentin, may influence the need for therapeutical intervention. Using a
      computerized technic, the depth of all approximal lesions in posterior teeth in
      151 persons, aged 20 and 23 years, were measured on magnified (x5) radiographs
      and expressed as per cent of the enamel width. The proportion diseased 20 year
      old persons was 88% if the criterion was any sign of caries but only 50% if the
      criterion was at least one lesion, reaching the dentin. When caries was defined
      as a lesion having a depth, corresponding the double enamel width the figure was
      11% and the proportion surfaces in need of therapeutical treatment constituted 2%
      of the total caries volume. It is concluded that an extension of the filling
      criterion into the superficial layers of the dentin may reduce the need for
      filling therapy in 20 year old persons to a very low level.

PMID- 8134894
TI  - 27 years of forensic odontology in Goteborg, Sweden.
AB  - The aim of this study was to analyze retrospectively all cases of forensic
      odontology during the period 1964-1990 in Goteborg. A total number of 281 cases
      were registered during a period of 27 years. The mean age of the victims was 39.5
      years and 73 per cent of the deceased persons were men. The identification cases
      dominated (274). A definitive identity was established in 207 cases (75.6%) and
      the identity could not be determined in 34 cases (12.4%). The causes of death
      were also analyzed. The total number of burned victims; in buildings, boats or
      cars was 84. Eighty-one persons were submersed in water. There were 49 victims of
      mutilation due to traffic accidents. Twenty-two persons were found in the wood.
      Seventeen persons died in their homes or abroad and were not found immediately
      after death and therefore the relatives were not asked to identify the decreased.
      There was no information about the cause of death in 21 cases.

PMID- 8134895
TI  - Analysis of paediatric dental services provided at a regional hospital in Sweden.
      Dental treatment need in medically compromised children referred for dental
      consultation.
AB  - All inpatients at a regional hospital in Sweden referred for a paediatric dental
      consultation (n = 269) were studied retrospectively during a two-year period. The
      children were studied concerning their medical and oral condition and subsequent
      dental treatment. The most frequent medical condition among the referred children
      was insulin dependent diabetes mellitus (20%), asthma (9%) and epilepsy (7%).
      Children with asthma exhibited a significantly increased caries prevalence (p <
      0.01) compared to other chronically sick children. Of the children examined 53%
      were diagnosed with diseases or abnormalities in the oral cavity requiring
      treatment. Gingivitis, disturbances in occlusal development and dental caries
      were the most commonly found diagnoses Acute dental or oral problems were
      diagnosed in 9% of the children. The mean time allocated for each patient was 60
      minutes. Thirty percent of the children were subsequently treated at the
      paediatric dentistry specialist clinic. In conclusion the study emphasises the
      need of paediatric dental consultation services at regional hospitals.

PMID- 8134896
TI  - Time-dependent changes in sensitivity to apomorphine and monoamine receptors
      following withdrawal from continuous cocaine administration in rats.
AB  - The effects of withdrawal from continuous administration of cocaine on behavioral
      sensitivity to apomorphine and monoamine receptor density were examined in rats.
      Subdermal minipumps that delivered either saline or 20 mg/kg/day cocaine
      hydrochloride were implanted for 2 weeks. Apomorphine-induced stereotypy (0.5
      mg/kg, SC) was examined in separate groups of rats either 4 hr or 7, 28, or 60
      days after removal of the minipumps. Transient enhanced sensitivity to
      apomorphine-induced stereotypy occurred during the course of withdrawal. Animals
      withdrawn from cocaine for 4 hours did not differ from controls in their
      sensitivity to apomorphine, whereas animals withdrawn from cocaine for 7 days
      exhibited an increase in apomorphine-induced oral stereotypy relative to
      controls. However, the enhanced stereotypy response was no longer evident in
      animals withdrawn for 28-60 days. The animals were sacrificed after behavioral
      testing, and their brains were assayed for changes in monoamine receptor density
      in the frontal cortex, caudate-putamen, and nucleus accumbens. The density of 3H
      SCH-23390-labeled D1 receptors was altered in all three regions examined in a
      time-dependent manner that paralleled the changes in behavioral sensitivity to
      apomorphine. There was a transient decrease in D1 receptor density that was
      evident by 7 days following withdrawal from continuous cocaine administration and
      was no longer evident 28 or 60 days posttreatment. There were no changes in 3H
      spiroperidol-labeled D2 receptors, 125-pindolol-labeled beta-adrenergic
      receptors, or 3H-ketanserin-labeled 5-HT2 receptors in any of the regions
      examined at both 4 hr and 7 days after termination of the cocaine infusion. These
      findings are discussed in terms of their relevance to developing pharmacologic
      treatments for withdrawal from cocaine.

PMID- 8134897
TI  - Long-term action of lithium: a role for transcriptional and posttranscriptional
      factors regulated by protein kinase C.
AB  - Lithium, a simple monovalent cation, represents one of psychiatry's most
      important treatments and is the most effective treatment for reducing both the
      frequency and severity of recurrent affective episodes. Despite extensive
      research, the underlying biologic basis for the therapeutic efficacy this drug
      remains unknown, and in recent years, research has focused on signal transduction
      pathways to explain lithium's efficacy in treating both poles of manic-depressive
      illness. Critical to attributions of therapeutic relevance to any observed
      biochemical effect, however, is the observation that the characteristic
      prophylactic action of lithium in stabilizing the profound mood cycling of
      bipolar disorder requires a lag period for onset and is not immediately reversed
      upon discontinuation of treatment. Biochemical changes requiring such prolonged
      administration of a drug suggest alterations at the genomic level but, until
      recently, little has been known about the transcriptional and posttranscriptional
      factors regulated by chronic drug treatment, although long-term changes in
      neuronal synaptic function are known to be dependent upon the selective
      regulation of gene expression. In this paper, we will present evidence to show
      that chronic lithium exerts significant transcriptional and posttranscriptional
      effects, and that these actions of lithium may be mediated via protein kinase C
      (PKC)-induced alterations in nuclear transcription regulatory factors responsible
      for modulating the expression of proteins involved in long-term neural plasticity
      and cellular response. Such target sites for chronic lithium may help unravel the
      processes by which a simple monovalent cation can produce a long-term
      stabilization of mood in individuals vulnerable to bipolar illness.

PMID- 8134898
TI  - Power spectral analysis of electroencephalographic desynchronization induced by
      cocaine in rats: correlation with microdialysis evaluation of dopaminergic
      neurotransmission at the medial prefrontal cortex.
AB  - We evaluated the effect and action mechanisms of cocaine on
      electroencephalographic (EEG) activity in adult male Sprague-Dawley rats
      anesthetized with chloral hydrate (400 mg/kg, i.p., with 80 mg/kg/h supplements).
      On-line and real-time power spectral analysis of the EEG activity continuously
      quantified its root mean square (RMS) and mean power frequency (MPF) values, and
      the power of its spectral frequency components (low frequency: 0-4 Hz; high
      frequency: 4-20 Hz). Administration of cocaine (1.5 or 3.0 mg/kg, i.v.) dose
      dependently induced EEG desynchronization, as manifested by a reduction in RMS
      and an elevation in MPF values, coupled with a differential decrease in both high
      and low frequency components. Samples collected by in vivo microdialysis at the
      medial prefrontal cortex (mPFC) and analyzed by HPLC showed that the elevation of
      cocaine and dopamine (DA) level in the dialysate reached its peak during the time
      interval when maximal activation of EEG occurred. This EEG activation was
      antagonized by microinfusion into the mPFC via reverse microdialysis of R(+)-SCH
      23390, a selective antagonist for D-1 receptors; sulpiride, a selective
      antagonist for D-2 receptors; or haloperidol, a nonspecific dopamine antagonist.
      These results suggest that dopaminergic neurotransmission at the mPFC may be
      intimately related to the specific spectral pattern of alteration in EEG activity
      elicited by cocaine in the rat and that both D-1 and D-2 receptors may be
      involved in the process.

PMID- 8134899
TI  - Systemic nicotine-induced dopamine release in the rat nucleus accumbens is
      regulated by nicotinic receptors in the ventral tegmental area.
AB  - Stimulation of the mesolimbic dopamine (DA) system is considered of major
      importance for the rewarding and dependence producing properties of nicotine
      (NIC). To identify the site of this stimulatory action, simultaneous
      microdialysis was performed in the ventral tegmental area (VTA) and the
      ipsilateral nucleus accumbens (NAC) of awake rats. Extracellular concentrations
      of DA and its metabolites were measured in the NAC. NIC (0.5 mg/kg, s.c.)
      increased DA and its metabolites by approximately 50%. Concomitant infusion of
      the nicotinic receptor antagonist mecamylamine (MEC, 100 microM) through the VTA
      probe, starting 40 min before NIC injection, antagonized the NIC induced
      increases of DA and its metabolites. In contrast, similar MEC pretreatment (40 or
      140 min) in the NAC did not affect DA or metabolite responses to systemic NIC.
      Infusion of NIC (1,000 microM) in the NAC or the VTA increased DA release by 49%
      and 48%, respectively, whereas only the VTA infusion increased metabolite
      concentrations by approximately 25%. MEC infusion (1-1,000 microM) in the VTA did
      not affect DA or its metabolites, whereas the 1,000 microM concentration infused
      in the NAC increased DA by 77%. These results suggest that nicotinic receptors in
      the somatodendritic region may be of greater importance than those located in the
      terminal area for the stimulatory action of systemic NIC on the mesolimbic DA
      system. Furthermore, our findings support the notion that the mesolimbic
      dopaminergic system is phasically rather than tonically regulated by nicotinic
      receptor activation within the VTA.

PMID- 8134900
TI  - "Strong" and "weak" synaptic differentiation in the crayfish opener muscle:
      structural correlates.
AB  - The single excitor motoneuron to the limb opener muscle in the crayfish
      Procambarus clarkii provides multiterminal innervation to individual muscle
      fibers. At low impulse frequencies, these neuromuscular synapses generate a
      threefold larger junctional potential in fibers of the proximal region of the
      muscle compared to those in the central region. Focal extracellular recording
      from synapse-bearing "boutons" showed more quantal release at low frequencies in
      the proximal region. Structural correlates for the physiological differences were
      sought. Fluorescence microscopy of surface innervation stained with a vital
      fluorescent dye, 4-Di-2-Asp, showed that density of innervation was not greater
      in the proximal region and thus could not account for the overall differences in
      synaptic strength. Freeze fracture studies showed that the intramembrane
      organization of excitatory synapses and their active zones was qualitatively
      similar in proximal and central sites. Serial section electron microscopy of
      several innervation sites in proximal and central regions showed homogeneity in
      number and size of synapses. However, presynaptic dense bars (at release sites,
      or active zones) were longer and occurred at a higher density in proximal than in
      central synapses. The differences in number and length of presynaptic dense bars
      correlate positively with the differences in synaptic strength represented by
      junctional potential amplitudes and quantal contents of individual surface
      recording sites. Since many individual proximal synapses have multiple dense
      bars, co-operativity among these may serve to enhance transmitter output. It is
      concluded that occurrence of dense bars is a significant presynaptic correlate of
      synaptic strength in this neuron.

PMID- 8134901
TI  - RTI-4793-14, a new ligand with high affinity and selectivity for the (+)-MK801
      insensitive [3H]1-]1-(2-thienyl)cyclohexyl]piperidine binding site (PCP site 2)
      of guinea pig brain.
AB  - [3H]TCP, an analog of the dissociative anesthetic phencyclidine (PCP), binds with
      high affinity to two sites in guinea pig brain membranes, one that is MK-801
      sensitive and one that is not. The MK-801-sensitive site (PCP site 1) is
      associated with NMDA receptors, whereas the MK-801-insensitive site (PCP site 2)
      may be associated with biogenic amine transporters (BAT). Although several "BAT
      ligands" are known that bind selectively to PCP site 2 and not to PCP site 1
      (such as indatraline), these compounds have low affinity for site 2 (Ki values >
      1 microM). Here we demonstrate that the novel pyrrole RTI-4793-14 is a selective,
      high affinity ligand for PCP site 2. We determined the IC50 values of RTI-4793-14
      and several reference compounds [PCP, (+)-MK801 and indatraline] for PCP site 1
      (assayed with [3H](+)-MK801), PCP site 2 (assayed with [3H]TCP in the presence of
      500 nM (+)-MK801) and a variety of BAT-related measures ([3H]CFT binding to the
      DA transporter, [3H]nisoxetine binding to the norepinephrine transporter,
      [3H]dopamine uptake, [3H]serotonin uptake). In addition, we determined the
      ability of RTI-4793-14 to block NMDA responses in cultured hippocampal neurons
      under voltage clamp. (+)-MK801 had high affinity for PCP site 1 (4.6 nM) and
      potently inhibited NMDA-induced responses, but was much less potent in the BAT
      related measures (IC50 s > 10 microM). PCP had high affinity at PCP site 1 (IC50
      = 92 nM) and PCP site 2 (IC50 = 117 nM), and was moderately potent in all BAT
      related measures except [3H]nisoxetine binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8134902
TI  - Enveloped axonal spines: a structural relationship between axons in the rat
      ciliary ganglion.

PMID- 8134903
TI  - Levels of plasma thrombomodulin are increased in atheromatous arterial disease.
AB  - The plasma thrombomodulin (TM) level depends on the integrity of the endothelium
      and the clearance of the molecule. In several different pathological conditions,
      plasma TM levels increase with damage to the endothelium. We studied plasma TM
      levels in patients with various localizations of atheromatous arterial disease
      who had normal serum creatinine levels. Two groups of patients had a single
      symptomatic localization, which was either peripheral occlusive arterial disease
      (POAD) or ischemic heart disease (IHD) and a third group of patients had multiple
      symptomatic localizations (polyvascular). We compared the plasma TM levels with
      the plasma levels of other specific markers of endothelial cell activation such
      as: prostacyclin (PGI2), tissue-type plasminogen activator (t-PA) and plasminogen
      activator inhibitor (PAI-1). Plasma TM levels were significantly increased in all
      three individual groups and when all patients were considered (total patients),
      as compared with normal controls. When all patients were considered, there was a
      significant positive correlation between plasma TM levels and t-PA and between
      plasma TM levels and PGI2. A significant positive correlation was also found
      between the plasma TM levels and PAI-1 for patients with POAD. Thus, our findings
      suggest that an increased influx of TM into the plasma may be caused by
      endothelial cell damage in patients with atheromatous arterial disease. However
      in our study, the plasma TM levels obtained were similar for all three types of
      atheromatous arterial disease. Though plasma thrombomodulin is a marker of
      endothelial cell injury, it cannot be of a clinical interest until its levels are
      related to the extend of the atheromatous lesions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8134904
TI  - Collagen-platelet interaction: separate receptor sites for types I and III
      collagen.
AB  - We have isolated a platelet membrane protein of M(r) 47 kDa which is responsible
      for the interaction of platelets with type III collagen. The 47 kDa protein was
      purified to apparent homogeneity by type III collagen-Sepharose 2B column
      chromatography and preparative slab gel electrophoreses. The 47 kDa protein
      blocked the adhesion of platelets to type III but not to type I collagen.
      Polyclonal antibodies were obtained from rabbits immunized with the purified 47
      kDa protein emulsified in complete Freund's adjuvant. The polyclonal antibodies
      inhibited the type III collagen but not type I collagen-induced platelet
      aggregation. The inhibitory effect of the antibodies on type III collagen-induced
      platelet aggregation was dose-dependent. Cross-inhibition on platelet aggregation
      studies showed that type I collagen receptor antibodies (M(r) 65 kDa) did not
      inhibit type III collagen-induced platelet aggregation and type III collagen
      receptor antibodies did not inhibit type I collagen induced platelet aggregation.
      These results suggest that type I and type III collagens interact with platelets
      at separate sites.

PMID- 8134905
TI  - Thrombin regulation of tissue-type plasminogen activator synthesis in cultured
      human fetal lung fibroblasts.
AB  - We examined the effects of thrombin on tissue-type plasminogen activator (t-PA)
      release and t-PA mRNA levels in cultured human fetal lung fibroblast cells, IMR
      90. The secretion of t-PA was increased by thrombin in a dose- and time-dependent
      manner, but it was not affected by inactivated thrombin with
      diisopropylfluorophosphate (DFP). Both antithrombin III (ATIII) and heparin
      cofactor II (HCII), plasma inhibitors to thrombin, inhibited thrombin-induced t
      PA release. The thrombin-induced t-PA secretion was preceded by an increase of
      the steady state level of t-PA-specific mRNA in the cells, suggesting that
      thrombin activates t-PA gene expression. The t-PA mRNA expression induced by
      thrombin was completely blocked by pretreatment of the cells with an inhibitor of
      translation, cycloheximide (CHX). These results suggest that the effect of
      thrombin on t-PA expression is mediated through its proteolytic activity and the
      biosynthesis of transcription factor(s).

PMID- 8134906
TI  - Evidence that plasma fibrinogen and platelet membrane GPIIb-IIIa are involved in
      the adhesion of platelets to an artificial surface exposed to plasma.
AB  - We investigated the molecular mechanism(s) by which platelets adhere to an
      artificial surface exposed to plasma, using polystyrene microtiter plates
      pretreated with plasma. Washed platelets labelled with 51Cr were incubated with
      the plates under static conditions. Prostaglandin E1(PGE1) was added to the
      platelets to prevent platelet-platelet interactions. Adhesion required the
      presence of a divalent cation such as Mg++ or Ca++. Polyclonal anti-fibrinogen
      antibody inhibited adhesion by 70%. Polyclonal antibodies against fibronectin,
      vitronectin, von Willebrand's Factor, and the Fc portion of human IgG, had no
      effect on adhesion. Platelets adhered normally to a surface pretreated with
      plasma from a patient with severe von Willebrand's disease. No platelet adhesion
      occurred when the surface was pretreated with an afibrinogenemic plasma.
      Monoclonal antibodies against platelet membrane GPIIb-IIIa, potent inhibitors of
      ADP-induced fibrinogen binding to platelets, completely inhibited adhesion.
      Monoclonal antibodies against the GPIb alpha subunit and GPIc(VLA alpha 5) showed
      no inhibitory effects on adhesion. Platelets from a patient with Glanzmann's
      thrombasthenia (type I) did not adhere to the surface pretreated with normal
      plasma. These results suggest that plasma fibrinogen adsorbed onto the surface
      and that platelet membrane glycoprotein(GP)IIb-IIIa were responsible for adhesion
      in an activation-independent manner.

PMID- 8134907
TI  - Enhanced endothelial tissue factor but normal thrombomodulin in endotoxin-treated
      rabbits.
AB  - Exposure of cultured endothelial cells to bacterial endotoxin induces an
      enhancement of cell procoagulant activity (PCA) and a simultaneous reduction of
      thrombomodulin activity (TM). We evaluated the effect of endotoxin on the
      expression of both endothelial PCA and TM in vivo, in rabbits. Animals were given
      a single i.v. injection of endotoxin (E. coli 0111:B4 LPS, W, 10-200
      micrograms/kg); the thoracic aorta was harvested after 2 or 4 hours and placed in
      an ad hoc device to expose the endothelial surface only. Endotoxin treatment
      resulted in a dose-dependent increase of endothelial PCA (p < 0.001, at 100
      micrograms/kg or more), which was totally dependent on factor VII and thus
      identified as tissue factor. In contrast, endothelial TM activity, as measured by
      the rate of thrombin-induced protein C activation, was similar in control and
      endotoxemic rabbits, even when the animals were given two injections (50
      micrograms/kg, 24 h apart), or a continuous infusion (40 micrograms/kg/h during 4
      hours) of endotoxin. To explore the effect of endotoxin on TM activity at the
      microcirculation level, we measured the extent of protein C activation in vivo,
      induced by a continuous infusion of low doses of thrombin (1 NIH U/kg/min for 60
      min). Again, endotoxin administration was not associated with significant changes
      in TM-dependent protein C activation, as assessed by the anticoagulant activity
      present in a barium citrate plasma eluate obtained at the end of thrombin
      infusion. Although reduction of TM during persistent endotoxemia cannot be
      definitively excluded, our data support a major role of endothelial PCA in LPS
      induced coagulative changes.

PMID- 8134908
TI  - Chelerythrine, a selective protein kinase C inhibitor, counteracts pyrogen
      induced expression of tissue factor without effect on thrombomodulin down
      regulation in endothelial cells.
AB  - Endotoxin, interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF
      alpha) dose-dependently increased the expression of tissue factor and at the same
      time induced thrombomodulin down-regulation on the surface of cultured bovine
      aortic endothelial cells. Chelerythrine, a selective protein kinase C inhibitor,
      strongly reduced endotoxin-, IL1 beta- and TNF alpha-induced tissue factor
      expression but remained without effect with regard to thrombomodulin down
      regulation measured in parallel. On the contrary, staurosporine, a highly potent,
      non-selective PKC inhibitor, simultaneously abolished tissue factor expression
      and thrombomodulin down-regulation induced by endotoxin, IL1 beta and TNF alpha.
      These results show that protein kinase C is deeply involved in the process
      leading to pyrogen-induced tissue factor expression and suggest that
      thrombomodulin down-regulation is regulated by a different pathway.

PMID- 8134909
TI  - Quantitation of platelet deposition on human arteries: assessment of the
      disparity between results obtained with 111indium (111In)-labelling versus
      scanning electron microscopy.
AB  - Quantitation techniques for measuring platelet deposition (PD) to vessel surfaces
      are important to an understanding of thrombogenesis. In previous studies,
      scanning electron microscopy (SEM) has been shown to indicate a lower extent of
      PD than platelet 111In-scintigraphy. Part of this disparity may be explained by
      nonspecific binding of 111In to the vessel surface during perfusion, or loss of
      adherent 111In-labelled platelets by lysis or dissociation from the surface
      during specimen preparation for SEM. To assess whether these independent
      processes occur, we used a previously described human placental artery (HPA)
      perfusion model to quantify vessel 111In retention. Of the total 111In that bound
      to the vessel surface during perfusion, 77 +/- 42% (N = 9) was platelet
      associated 111In (111In-labelled platelets) and 23 +/- 19% (N = 9) was non
      platelet associated 111In (nonspecific binding). After specimen fixation, 67 +/-
      32% (N = 9) of the initial total surface 111In remained. This decrease is due to
      dissociation of both adherent 111In-labelled platelets, and nonplatelet
      associated 111In. After fixation, 57 +/- 34% (N = 9) of the initial total surface
      111In remained as 111In-labelled platelets and 10 +/- 13% (N = 9) remained as
      nonplatelet associated 111In. Fixation caused no measurable lysis of platelets.
      These data suggest that PD may be overestimated by 111In-scintigraphy because of
      nonspecific binding of 111In and underestimated by SEM because of dissociation of
      adherent platelets during specimen preparation for SEM.

PMID- 8134910
TI  - Parkia biglobosa seeds possess anti platelet activity.

PMID- 8134912
TI  - [A farm with paratuberculosis].

PMID- 8134911
TI  - [Streptococcal infections as cause of death in pigs brought in for necropsy].
AB  - Research was carried out into the prevalence of streptococcal types isolated from
      pigs that died of septicaemia, meningo-encephalitis, endocarditis, and pneumonia
      and which were brought in for investigation from 1 january 1988 to 31 December
      1991. Cultures were prepared from the liver, spleen, kidneys, and brains of all
      animals and from the heart valves, joints, bronchi, and lungs of animals with
      pathological changes. The results are presented in six tables. As a group,
      streptococci were a major source of bacterial infection in septicaemia (38%),
      meningo-encephalitis (21%), and endocarditis (74%). Of the streptococcus types.
      Streptococcus suis type 2 was isolated the most often in sepsis (36%), meningo
      encephalitis (52%), and endocarditis (36%). Streptococcus suis type 1 was found
      not only in piglets up to the age of weaning but also in older pigs and was a
      common pathogen in pigs with endocarditis. The discussion takes into
      consideration data from the literature. It is concluded that the significance of
      streptococcus infections, and those involving Streptococcus suis types 1 and 2 in
      particular, has increased under the influence of environmental and management
      factors (scaling-up of production, import of pigs from abroad, extermination and
      control of other pig diseases).

PMID- 8134913
TI  - [A male Kooiker. What is your diagnosis? Subcorneal pustular dermatosis (SPD)].

PMID- 8134914
TI  - [Predecessors: veterinarians from earlier times--Absyrtus].

PMID- 8134915
TI  - [Between hammer and hole. Interview by Sophie Deleu].

PMID- 8134916
TI  - [A castrated tom-cat in shock].

PMID- 8134917
TI  - Genotoxicity of the phosphoramidate agent tabun (GA).
AB  - Five mutagenicity tests were performed on Agent GA (Tabun, phosphoramidocyanidic
      acid, dimethyl-, ethyl ester) as part of a program to demilitarize chemical
      warfare agents. GA was mutagenic in Salmonella spp. assays with S-9 and it was a
      direct-acting mutagen to mouse lymphoma cells. GA did not promote unscheduled DNA
      synthesis in rat hepatocytes; it induced sister chromatid exchanges in mouse
      cells in vitro but in vivo. The conclusion that GA is a weakly acting mutagen is
      supported by the fact that it was mutagenic in only three of the five assays, and
      that increases in mutagenicity were often less than 2-fold the controls and
      occurred near toxic levels.

PMID- 8134918
TI  - Induction of cytochrome P4504A by the peroxisome proliferator perfluoro-n
      octanoic acid.
AB  - The influence of a single dose of the peroxisome proliferator, perfluoro-n
      octanoic acid (PFOA) on hepatic and renal mixed-function oxidase activities has
      been examined in rats. Peroxisome proliferation was confirmed by increases in
      peroxisomal palmitoyl-CoA oxidation and carnitine acetyl transferase activity,
      particularly in liver. The liver was also more susceptible than the kidney to
      PFOA-dependent induction of the 12-hydroxylation of lauric acid, suggesting
      induction of the CYP4A sub-family. This was further confirmed by Western blot
      analyses, wherein an anti-CYP4A1 antibody revealed a substantial PFOA-dependent
      induction of CYP4A1 in a pattern similar to that observed for the classical
      peroxisome proliferator, clofibrate. In addition, using a cDNA probe to CYP4A1 in
      Northern blot analysis, PFOA treatment resulted in a marked increase in the
      steady state level of CYP4A1 mRNA, again more extensively in liver than in
      kidney. Taken collectively, our data provide compelling evidence that PFOA, like
      other peroxisome proliferators, is also an inducer of the CYP4A subfamily.

PMID- 8134919
TI  - Cytotoxicity of dust constituents towards alveolar macrophages: interactions of
      heavy metal compounds.
AB  - The interactions between different heavy metal compounds which affect their
      cytotoxicity towards rabbit alveolar macrophages were investigated. The cells
      were exposed in vitro to combinations of As3+, Cd2+, Hg2+, Ni2+, or V5+ with
      different concentrations of another heavy metal compound. Toxicity was determined
      as the depression of zymosan-induced release of superoxide anion radicals.
      Significant antagonisms occurred in the combinations Cd2+/Zn2+, Hg2+/As3+, and
      Hg2+/Se4+, while significant synergisms were exhibited by the combinations
      Cd2+/Cu2+, Cd2+/Sn2+, Hg2+/Cu2+, Ni2+/Cd2+, Ni2+/Cu2+, Ni2+/Sn2+ and V5+/Cu2+. In
      the combinations As3+/Zn2+, Hg2+/Cd2+ and Hg2+/Zn2+, both kinds of interactions
      were observed depending on the concentrations of the heavy metal compounds. An
      interpretation of the measured heavy metal interactions with reference to the
      toxicity of heavy metal-containing dusts is attempted.

PMID- 8134920
TI  - Effect of 3-phenylamino-L-alanine on tryptophan binding to rat hepatic nuclear
      envelopes.
AB  - We have determined that the addition of 3-phenylamino-L-alanine (PAA), a recently
      reported contaminant in L-tryptophan implicated in the eosinophilia-myalgia
      syndrome, affects tryptophan binding by utilizing an in vitro measurement of 3H
      tryptophan binding to hepatic nuclei or nuclear envelopes. PAA (10(-10) to 10(-4)
      M) diminishes the inhibitory effect of binding due to excess unlabeled L
      tryptophan (10(-4) M). PAA alone has no inhibitory effect on binding. The effect
      of PAA on in vitro tryptophan binding is in contrast to that of another
      contaminant, 1,1'-ethylidenebis(tryptophan), which together with excess unlabeled
      L-tryptophan does not appreciably affect the binding. In vitro addition of PAA
      and L-tryptophan to nuclei of rat brain or of cultured murine macrophages does
      not affect [3H]tryptophan binding in comparison to L-tryptophan alone as is the
      case with hepatic nuclear envelopes. Adding PAA to an in vitro protein synthesis
      system and measuring [3H]tryptophan or [3H]alanine incorporation into acid
      precipitable proteins reveals that it competes similarly, but somewhat less, than
      does equimolar concentrations of unlabeled L-tryptophan or L-alanine,
      respectively. This suggests that PAA or a breakdown compound becomes incorporated
      into proteins. Speculation as to how PAA may affect tissues in experimental
      animals is presented.

PMID- 8134921
TI  - Dithiothreitol reversal of allyl alcohol cytotoxicity in isolated rat
      hepatocytes.
AB  - Reversal by dithiothreitol (DTT) of allyl alcohol cytotoxicity was investigated
      in isolated rat hepatocytes. Allyl alcohol-induced protein sulfhydryl loss, bleb
      formation, and cell death were prevented by DTT, when it was added to hepatocytes
      30 min after the toxicant. The protective effect of DTT also was demonstrated in
      cells that were washed after 30 min of exposure to allyl alcohol, indicating that
      protection was not related to inhibition of allyl alcohol metabolism or
      inactivation of acrolein. DTT reversed the cell surface protrusions that formed
      during exposure to allyl alcohol, but reversal of blebbing did not insure that
      the cells would remain viable. Glutathione disulfide was not formed in allyl
      alcohol-treated cells, and DTT reversal of cytotoxicity occurred without
      restoring glutathione levels. Moreover, protection against allyl alcohol toxicity
      required the continuous presence of DTT. The results suggest that initial events
      in the toxic process are reversible, and that DTT can prevent cytotoxicity if
      added to hepatocytes before irreversible damage occurs; however, the mechanism by
      which DTT exerts its protection is not clear.

PMID- 8134922
TI  - Protective effects of 2,3-dimercaptopropane-1-sulfonate on mercuric chloride
      induced acute inhibition of enzymes from rat duodenal mucosa and kidney cortex.
AB  - Acute inhibitory effects of mercuric chloride on the activities of several
      enzymes from rat duodenal mucosa and kidney cortex and the protection provided by
      2,3-dimercaptopropane-1-sulfonate (DMPS) were examined. Activities of carbonic
      anhydrase in homogenate, brush border and cytosol and of Mg(2+)-dependent, HCO3
      stimulated ATPase in homogenate and brush border of duodenal mucosa and kidney
      cortex and activities of kidney microsomal Mg(2+)-dependent, Na(+)-K(+)
      stimulated ATPase were all decreased following administration of HgCl2 (1-3 mg
      Hg/kg body weight s.c. once daily for 3 days). Decreases occurred generally in a
      dose-dependent manner and went back to near normal or normal levels by the
      combined administration of 20 and 30 mg DMPS/kg per day for 3 days. The
      concentration of serum urea nitrogen was increased about 8 times by the
      administration of 2 mg Hg/kg and restored to normal by the concomitant
      administration of 30 mg DMPS/kg. After the administration of 2 mg Hg/kg per day
      for 3 days, about half of the renal cortical proximal tubuli were necrotic.
      Administration of 30 mg DMPS/kg restored these changes to almost normal. The
      results suggest that DMPS is useful in mitigating acute Hg poisoning and that
      part of the protective effect of DMPS on enzyme damage induced by Hg poisoning
      may be due to its chelating action.

PMID- 8134923
TI  - Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether
      (DE-71) in C57BL/6J mice.
AB  - Polybrominated diphenyl ethers are manufactured for use as flame retardants in
      commercial plastics and textiles in Europe and North America. These studies
      investigated the acute and subchronic immunotoxicity and endocrine effects of a
      commercial pentabromodiphenyl either mixture, DE-71, in female C57BL/6 mice. Mice
      were orally exposed to acute single doses of DE-71 of 0, 0.8, 4.0, 20, 100, or
      500 mg/kg, or to subchronic daily doses totaling 0, 250, 500, or 1000 mg/kg over
      a 14 day period. Immunotoxicity was assessed by measuring the plaque-forming cell
      response to sheep erythrocytes (SRBC) and natural killer cell (NKC) activity
      (basal and poly I:C stimulated) to YAC-1 target cells. Liver cytochrome P450
      content and activities (ethoxyresorufin-o-deethylase (EROD) and pentoxyresorufin
      o-deethylase (PROD)) as well as corticosterone (CS) and thyroxine (T4)
      concentrations were also measured. PROD activity was induced 3-5-fold in mice
      exposed acutely or subchronically to DE-71 at doses > 250 mg/kg. EROD activity
      and total microsomal cytochrome P450 content were significantly induced only in
      mice treated subchronically with DE-71; maximum induction of EROD was 3.3-fold.
      Total serum T4 concentrations were significantly lower in mice treated acutely
      with DE-71 at all doses except the 100 mg/kg dose. Total and free T4
      concentrations were dose-dependently decreased in DE-71-treated mice following
      subchronic exposure. Plasma CS levels were elevated following subchronic exposure
      to DE-71. The elevation of CS was correlated with order of capture at necropsy,
      suggesting an interactive effect of DE-71 and stress. In regard to
      immunotoxicity, significant suppression of the anti-SRBC response was seen only
      in mice exposed subchronically to 1000 mg DE-71/kg, an exposure that also
      resulted in decreased thymus weight. NKC activity was not altered by exposure to
      DE-71.

PMID- 8134924
TI  - Decreases in dopamine concentrations in adult, non-human primate brain persist
      following removal from polychlorinated biphenyls.
AB  - Adult male non-human primates, Macaca nemestrina, were orally exposed for 20
      weeks to 3.2 mg/kg per day of either Aroclor 1016 or Aroclor 1260 made up in corn
      oil. Following cessation of exposure, the animals were observed for either an
      additional 24 or 44 weeks. After killing, regional brain concentrations of
      biogenic amines and polychlorinated biphenyls were determined by high-performance
      liquid chromatography (HPLC) and gas chromatography (GC), respectively. Brain
      dopamine (DA) concentrations were significantly decreased, compared to controls,
      in all polychlorinated biphenyl-exposed animals. Most importantly, in spite of
      significant decreases in brain polychlorinated biphenyl concentrations observed
      following removal from exposure (an average decline of 60%), there was no
      statistically discernible relationship of the changes in brain DA concentrations
      to either time following removal from polychlorinated biphenyls or brain
      polychlorinated biphenyl concentrations. These findings demonstrate that sub
      chronic exposure of the adult non-human primate to polychlorinated biphenyls
      results in long-lasting changes in brain DA concentrations.

PMID- 8134925
TI  - Arylation of sulfhydryl groups in vitro by the naturally occurring
      sesquiterpenoid benzoquinone avarone.
AB  - Avarone (AQ) is a naturally occurring sesquiterpenoid benzoquinone possessing
      antileukaemic activity. Its reactivity towards glutathione (GSH) and protein
      sulfhydryl (SH) groups was investigated. The stoichiometry of AQ reaction with
      GSH at [GSH]/[AQ] ratios lower than unity proved to be 1:2 (thiol:quinone),
      consistent with the formation of the corresponding hydroquinone (avarol) as well
      as a quinone-thioether in the reaction. Conversely, when the [GSH]/[AG] ratio was
      higher than unity, a hydroquinone-thioether was the only reaction product.
      AQ/protein interaction was also investigated by using bovine serum albumin (BSA)
      as model compound. As observed with GSH, arylation rather than oxidation of SH
      groups appeared to be the mechanism responsible for the AQ-induced depletion of
      protein SH groups. However, AQ proved to be less effective in depleting BSA
      sulfhydryls than that of GSH. AQ disappearance after BSA addition was greater
      than expected on the basis of the total SH groups depleted, if a stoichiometric
      ratio 1:2 (thiol:quinone) was assumed. It also occurred in the presence of BSA
      with blocked SH groups, thus suggesting that AQ may react with other nucleophilic
      protein residues, such as amino or imino groups. When HepG2 cells were exposed to
      AQ, depletion of both protein SH groups and GSH occurred. However, in contrast to
      the above, AQ proved to be more effective, probably because of its lipophilic
      nature, in depleting protein SH groups than GSH. Also, in intact cells AQ
      appeared to arylate both SH and other nucleophilic groups in proteins. This
      mechanism may play a major role in AQ-induced cytotoxicity.

PMID- 8134926
TI  - Platelets tested at 25 degrees C have greater aggregation reactivity to ADP than
      those tested at 37 degrees C.

PMID- 8134927
TI  - War and health--a view of Africa.

PMID- 8134928
TI  - Limitations of the WHO/CDC clinical case definition for AIDS in Africa.

PMID- 8134929
TI  - The Kasongo project: a case study in community participation.

PMID- 8134930
TI  - Adi Quala: application of solar photovoltaic generation in rural medical centres.
AB  - Adi Quala is an Eritrean agricultural town of 14,000 people, and is situated
      about 70 km south of the capital, Asmara and 30 km from the border with Tigray,
      Ethiopia. On good days electricity was received from Asmara between 0600 h and
      2300 h with nothing available outside these hours. These conditions meant the
      electricity supply had been a constant problem for the Adi Quala hospital which
      caters for about 50,000 people with 21 staff. It was for this reason that it was
      chosen for the first solar system, which provides all essential requirements
      completely independently from the grid connection. This will in turn enable the
      hospital to increase the range and reliability of services on offer. Three weeks
      after the arrival of the equipment the elders were able to have a guided tour of
      their new local facilities. This included 2kW of photovoltaic panels (installed
      on the roof), batteries and control equipment powering a range of hospital
      equipment used in the Mother and Child Health Centre, delivery room, wards,
      dispensary, clinic and laboratory. Their enormous appreciation was very moving
      and well articulated in an afternoon of music, speeches and feasting. Eritrea's
      first solar powered hospital was welcomed into capable hands. The pilot project
      was successfully installed and commissioned in February 1992, and has performed
      well to date.

PMID- 8134931
TI  - The treatment of supracondylar fractures by ambulatory traction.

PMID- 8134932
TI  - The home-based health passport: a tool for primary health care.

PMID- 8134933
TI  - The electronic stadiometer: an appropriate technology for height measurement in
      health surveys.

PMID- 8134934
TI  - The Cameroon.

PMID- 8134936
TI  - Managing district finances.

PMID- 8134937
TI  - An epidemic in Guinea Bissau.

PMID- 8134935
TI  - Depressive illness--Zimbabwe.
AB  - Depression is common in the developing world and accounts for 10-20% of
      attendances at primary care clinics. It is a condition associated with
      considerable morbidity. This paper considers the characteristics of depressive
      illness in Zimbabwe and discusses ways to improve detection and management.

PMID- 8134938
TI  - Is intrarectal injectable quinine a safe alternative to intramuscular injectable
      quinine?

PMID- 8134939
TI  - Ivermectin: obstacles to community-based distribution in the Dingila health zone
      in northeastern Zaire.

PMID- 8134940
TI  - Health workers' attitudes to a hospitalized AIDS patient in Ile-Ife, Nigeria:
      urgent need for intervention.

PMID- 8134941
TI  - Traditional healing.

PMID- 8134942
TI  - Tuberculosis.

PMID- 8134943
TI  - Comparative study of two transport systems for Vibrio cholerae.

PMID- 8134944
TI  - Corticosteroids and tuberculosis chemoprophylaxis.

PMID- 8134945
TI  - Reusable needles--a major risk factor in acute virus B hepatitis.

PMID- 8134946
TI  - Rare poisoning with cerebra thevetia (yellow oleander): a report of three cases.

PMID- 8134947
TI  - An unusual surgical complication of traditional scabies prevention measures.

PMID- 8134948
TI  - Ventricular septal defect with endocarditis caused by Salmonella paratyphi A.

PMID- 8134949
TI  - Mucormycosis (zygomycosis).

PMID- 8134950
TI  - An unusual case of Yersinia pseudotuberculosis-induced diarrhoea in Mangalore,
      south India.

PMID- 8134951
TI  - Primary amoebic appendicitis.

PMID- 8134952
TI  - Ureterosigmoidostomy?

PMID- 8134953
TI  - The poor cousin of medicine.

PMID- 8134954
TI  - Financial management in times of severe resource constraints: the role of the
      district manager.

PMID- 8134955
TI  - [Severe asthma].

PMID- 8134956
TI  - [Watermelon stomach].

PMID- 8134957
TI  - [Long term postoperative course of aortic insufficiency (80 cases)].

PMID- 8134958
TI  - [Electroencephalography in epileptic children: value and limits: 317 cases].

PMID- 8134959
TI  - [Hemorrhages at delivery: 145 cases observed at the maternity department of
      Bizerte and the new Habib Thameur University Hospital Center].

PMID- 8134960
TI  - [Problems posed during the management of ocular complications of diabetes].

PMID- 8134962
TI  - [Contribution of scintigraphy in the study of pulmonary perfusion].

PMID- 8134961
TI  - [Serious ocular accidents in the professional milieu].

PMID- 8134963
TI  - [Epidermal verrucous linear inflammatory hamartoma (3 cases)].

PMID- 8134964
TI  - [Anomaly of the biliopancreatic junction associated with Caroli's disease: a case
      report].

PMID- 8134965
TI  - [Ugeskrift for Laeger: 1993 index].

PMID- 8134966
TI  - The history of ultrasound techniques in ophthalmology.
AB  - The history of 50 years of applications of ultrasound in ophthalmology is
      described. This period started in 1938 with a study of the possible effects of
      high intensity ultrasound on eyes. The measurement of biological effects for the
      assessment of potential hazards characterizes the first decades. More recently,
      the therapeutic use of ultrasound by hyperthermia has gained much interest in
      ophthalmology. Further topics are: the measurement of acoustic characteristics of
      ocular tissues; the biometry of the eye ball, the results of which are used to
      calculate the optical power of artificial lens implants; the development of
      diagnostic instruments in various parts of the world; and ultrasonic tissue
      characterization for the differential diagnosis of pathology. The final topic is
      concerned with some recent developments which present a look into the future.

PMID- 8134967
TI  - Myocardial regional blood flow: quantitative measurement by computer analysis of
      contrast enhanced echocardiographic images.
AB  - Quantitation of regional myocardial blood flow constitutes the missing link
      between the anatomy of coronary obstruction and its physiological effect on
      regional oxygen supply. Microscopic air bubbles, introduced into the coronary
      circulation, were shown to produce a transitory enhancement of the myocardial
      tissue contrast, easily detectable with standard ultrasonic imaging equipment.
      This study presents a new approach linking the tissue blood flow with the time
      dependent changes in the intensity of the ultrasonic reflections produced by the
      microbubbles. The tissue blood flow is evaluated using the well-known indicator
      dilution relation, according to which flow equals the ratio between the
      intravascular fraction of the tissue sample volume and the mean transit time of
      the contrast agent. We derive these two parameters from the time curves
      representing the contrast induced variations in the mean videointensity measured
      in two regions of interest, a reference region in the left ventricular cavity and
      the region of interest within the myocardial tissue. The intravascular volume
      fraction is computed as the ratio of the total power of the above two intensity
      curves, as each of these is assumed to be proportional to the total amount of
      tracer traversing the corresponding region of interest. The mean transit time is
      computed using combined time- and frequency-domain processing, involving Fourier
      deconvolution of the response function of the myocardial tissue sample. This
      approach was validated in an in vivo model in a series of animal experiments
      involving left atrial injection of albumin coated air microbubbles (Albunex).
      Videointensity curves obtained during contrast enhancement of the myocardium were
      analyzed to provide values of regional myocardial blood flow (in mL/min/100 g) in
      45 myocardial regions of interest defined in 7 experiments performed on 4
      animals. The values obtained with our approach correlated well (r = 0.77, p <
      0.001) with standard reference measurements based on radiolabeled microspheres.
      The intertechnique variability was found to be smaller than the intersegment
      variability characterizing our technique. The difference between the mean flow
      values obtained with microspheres for segments of the entire heart and the mean
      flow obtained with our technique for all regions of interest ranged between 1 to
      19% in the 7 experiments. In its present form, based on left atrial or left
      ventricular injection of contrast solution, this method may allow, for the first
      time, quantitative evaluation of myocardial regional blood supply in the cardiac
      catheterization laboratory or the operation theater.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8134968
TI  - Myocardial transit time of the echocardiographic contrast media.
AB  - The mean transit time of a tracer through a sample of tissue is a quantitative
      marker most closely related to regional tissue blood flow. Therefore, an accurate
      estimation of the mean time of transit of an ultrasonic tracer through a sample
      of myocardial tissue, obtained by contrast echocardiography, may provide a
      quantitative noninvasive estimate of myocardial perfusion. We hereby present an
      algorithm for the determination of the mean transit time by computerized analysis
      of a series of contrast-enhanced echocardiographic images. The algorithm
      comprises the evaluation of the echocardiographic impulse response function of a
      selected region of interest, using a deconvolution technique based on a fast
      Fourier transform and a frequency domain division of the videointensities
      measured in the sample, by that measured in a predetermined reference region. An
      extensive computer simulation study was designed to facilitate the optimization
      of the steps of analysis. We present the results of the evaluation study
      performed in order to assess the accuracy of the procedure in computer-simulated
      echocardiographic images. Within a wide range of parameters chosen to define
      these functions, the analysis is shown to be essentially independent of the rise
      and decay times of the impulse response function of the tissue sample as well as
      of the simulated intensities. The effects of random noise introduced into the
      simulated intensity curves and of their variable width were investigated. The
      mean transit time was found to be accurately evaluated within about 10% of error
      for the variety of widths and noise levels permitted. The reconvolution error did
      not correlate with the accuracy of the evaluation of the mean transit time,
      indicating that the reconvolution error cannot be used as an estimate of the
      accuracy of the procedure. The numerical methods and the results of the computer
      study are discussed in detail. The approach is proposed to be used as part of a
      more general technique for the quantitative measurement of regional myocardial
      tissue blood flow.

PMID- 8134969
TI  - Doppler ultrasound spectral shape in the poststenotic velocity field.
AB  - The shape of averaged and smoothed pulsed Doppler spectra from the shear layer
      between jet and recirculation zones, one diameter downstream of three acrylic
      stenosis (27, 47 and 65% diameter reduction) in a steady flow dialysis tubing
      model, were found to be complex. Their shape contrasted with the shape of spectra
      from regions of jet breakup. The latter had a shape suggesting a Gaussian
      distribution of apparent velocities consistent with varying magnitude and
      direction in turbulent flow. In contrast, the least complex spectra from the
      shear layer had a double-peaked shape suggestive of two distinct major velocity
      components or streamline groups. A subtraction method was used to resolve the
      least complex spectra into two relatively narrow Gaussian components. More
      complex spectra could be resolved into multiple components by serially
      subtracting individual Gaussian components. Comparison with the pattern of
      particles revealed by flow visualization studies suggests that most of the
      components are due to axially directed streamline groups of different velocities
      but that some may be due to radially directed streamline groups. Broadened
      spectral components, which are apparent at higher flow rates, are consistent with
      development of vortices in the shear layer.

PMID- 8134970
TI  - Fractal concept and its analysis method for Doppler ultrasound signals.

PMID- 8134971
TI  - Temperature elevation in focused Gaussian ultrasonic beams at various insonation
      times.
AB  - Transient solution of the thermal conductivity equation for the three-dimensional
      case of the Gaussian ultrasonic focused beam was derived and applied for cases
      relevant to medical ultrasonography. Quantitative results for the case of a
      homogeneous medium with constant values of thermal coefficients and constant
      absorption as well as for the two-layer tissue model used in obstetrics were
      presented for various diagnostic probes used in ultrasonography. The possible
      effects of perfusion and nonlinear propagation were neglected. The results
      obtained are in agreement with results of other authors when considering the
      steady-state and the infinitely short insonation time. The computations show the
      influence of the insonation time on the temperature elevation, thus making it
      possible to introduce its value as a factor in limiting the possible harmful
      effects in ultrasonography. This has been shown in diagrams presenting the
      temperature distribution along the beam axis of 6 different diagnostic probes for
      various insonation times and demonstrating the corresponding temperature decrease
      when limiting the insonation time to 5 and 1 min. For instance, the highest
      temperature elevation (for probe number 1, see Table 1) decreases 2.6 and 5 times
      with respect to the steady-state temperature when the insonation time equals 5
      and 1 min, respectively.

PMID- 8134973
TI  - Small arteries can be accurately studied in vivo, using high frequency
      ultrasound.
AB  - We have validated measurements of diameters of the superficial temporal artery
      and other small arteries in man with a newly developed 20 MHz ultrasound scanner
      with A, B and M-mode imaging. The diameter of a reference object was 1.202 mm vs.
      1.205 mm as measured by stereomicroscopy (nonsignificant). In vitro measurements
      of porcine carotid arteries could be reproduced with a mean interobserver
      difference of 0.008 mm, and the repeatability coefficient was 0.04 mm (1.4%). The
      frontal branch of the human superficial temporal artery (mean 1.24 mm) was
      measured with intraobserver repeatability coefficients of 0.18 mm (13.8%) to 0.31
      mm (23.4%). The interobserver mean difference was 0.01 mm (0.69%) and the
      interobserver repeatability coefficient was 0.16 mm (11.1%). Pulsatile changes of
      the cross sectional area of the radial plus the ulnar artery averaged 0.93 mm2
      compared to 0.63 mm2 by strain-gauge plethysmography (nonsignificant). Pulsations
      were 4.6% in the radial artery. We conclude that high frequency ultrasound
      provides an accurate and reproducible measure of the diameter of small and medium
      sized human arteries in vivo.

PMID- 8134972
TI  - Aortic compliance measurements using Doppler ultrasound: in vivo biochemical
      correlates.
AB  - A noninvasive Doppler ultrasound technique for the assessment of aortic
      compliance based on the in vivo measurement of pulse wave velocity along the
      thoraco-abdominal aortic pathway is described. An approach for correcting for the
      effect of blood pressure on aortic distensibility is considered. The derivation
      of an index of intrinsic distensibility, Cp, which is independent of blood
      pressure, is provided and applied to data collected from normal, healthy
      volunteers. Overviews are provided of studies utilising the technique to
      determine aortic compliance in medical disorders, which are known to predispose
      to premature cardiovascular disease, such as diabetes mellitus, familial
      hypercholesterolaemia and growth hormone deficiency. The significance of
      correlations between in vivo aortic compliance measurements and plasma
      concentrations of total cholesterol, low-density-lipoprotein cholesterol, high
      density-lipoprotein cholesterol and insulin-like growth factor-I are discussed.
      It is proposed that the measurement of aortic compliance in normal, healthy
      individuals may potentially be a useful in vivo research tool for investigating
      the effects of biochemical factors on the biophysical properties of the aortic
      wall. Furthermore, we believe that the routine measurement of blood pressure
      corrected aortic distensibility may prove a useful, noninvasive clinical tool for
      assessing patients' susceptibility to atherosclerosis, as well as for monitoring
      their response to therapeutic interventions.

PMID- 8134974
TI  - Comparison of the performance of the RF cross correlation and Doppler
      autocorrelation technique to estimate the mean velocity of simulated ultrasound
      signals.
AB  - In pulsed Doppler systems the received RF (radio frequency) signal is multiplied
      by a quadrature reference signal and subsequently averaged over a short depth
      range to obtain a sample of the complex Doppler signal. The mean frequency of the
      sampled Doppler signal, obtained with the autocorrelation function, reflects the
      mean velocity of the scatterers moving through the sample volume. An alternative
      is to evaluate the two-dimensional cross correlation function of a short segment
      of the RF signals over subsequent lines, giving the mean velocity of the
      scatterers. Both methods of velocity estimation were applied to computer
      generated RF signals with varying RF bandwidth, signal-to-noise ratio, and mean
      and width of the imposed velocity distribution. The length of the RF signal
      segment and the number of lines for velocity estimation (package length) affects
      the accuracy of the velocity estimate. It can be concluded that the cross
      correlation technique behaves superiorly especially for a low velocity
      dispersion. Furthermore, the standard deviation of the velocity estimate
      decreases for an increasing sample volume length and package length, while the
      performance of the conventional Doppler technique is rather independent of the
      length of the sample volume. The difference between both techniques decreases for
      a greater package length or for signals simulating a wide velocity distribution.

PMID- 8134975
TI  - Range/velocity limitations for time-domain blood velocity estimation.
AB  - The traditional range/velocity limitation for blood velocity estimation systems
      using ultrasound is elucidated. It is stated that the equation is a property of
      the estimator used, not the actual physical measurement situation, as higher
      velocities can be estimated by the time domain cross-correlation approach. It is
      demonstrated that the time domain technique under certain measurement conditions
      will yield unsatisfactory results, when trying to estimate high velocities.
      Various methods to avoid these artifacts using temporal and spatial clustering
      techniques are suggested. The improvement in probability of correct detection is
      derived, and several examples of simulations are shown.

PMID- 8134976
TI  - A real time system for quantifying and displaying two-dimensional velocities
      using ultrasound.
AB  - This paper describes a system that has been developed for measuring two
      dimensional velocities in real time using ultrasound. The instrument tracks
      interframe speckle pattern motion using a Sum-Absolute-Difference (SAD) algorithm
      in order to produce a vector map of 2D velocities. The system's parallel
      architecture allows calculation of approximately 20,000 vectors per second using
      the current tracking geometry. A programmable graphics processor encodes
      individual velocity vectors with color and displays them superimposed on the B
      mode image in real time. In vitro tests indicate that the system can track
      velocities well over the Doppler aliasing limit in any direction in the scan
      plane with greater than 94% accuracy. A color encoded image obtained from a flow
      phantom highlights the system's ability to display lateral motion with uniform
      coloration, in contrast to the two-color display of current ultrasonic Doppler
      instruments.

PMID- 8134977
TI  - Correction of phase aberrations for sectored annular array ultrasound
      transducers.
AB  - Two methods for correction of unknown phase aberrations induced by inhomogeneous
      acoustic velocities in tissues are explored for the two dimensional geometry of a
      sectored annular array system. The methods employed are adaptations of a cross
      correlation technique and a speckle brightness maximization technique. The
      methods correct phase distortions via the introduction of phase shifts in the
      timing sequence at the beamformer stage of a sectored annular array transducer.
      The techniques are investigated employing software models and a computer
      controlled automated scanning system. A 65-element sectored annular array is
      modelled via a rotating 5 element transducer. Tissue equivalent materials were
      moulded into a double layer aberrating medium to simulate phase distortions
      encountered in the rectus abdominis muscle in vivo. A comparison of the
      effectiveness of the two correction methods is presented. Contrast of an anechoic
      region is increased from 0.34 +/- 0.08 to 0.48 +/- 0.06 for the cross correlation
      technique, and up to 0.62 +/- 0.05 for the speckle brightness maximization
      method. The performance of these correction techniques on target phantoms
      suggests that considerable improvements in image quality should be possible for
      clinical systems.

PMID- 8134978
TI  - Focal spacing and near-field heating during pulsed high temperature ultrasound
      therapy.
AB  - It has been proposed that high temperature short duration hyperthermia treatment
      would be perfusion insensitive and thus, significantly improved thermal exposure
      uniformity could be achieved. This study investigates the execution of such a
      treatment, which utilizes single spherically curved transducer and multiple
      sonications to cover the complete target volume. The spacing of neighboring
      pulses as a function of the transducer characteristics was studied utilizing
      computer simulations. In addition, the temperature elevation in front of the
      focal zone during multiple sonications was evaluated. It was found that
      significant delays (20 s or longer) between the sonications must be introduced in
      order to avoid unwanted tissue damage in front of the focal zone. In addition,
      decreasing the pulse duration and F-number reduced the temperature build-up in
      front of the focus. The results were verified in vivo in dog's thigh muscle. This
      study is important not only for hyperthermia but also for ultrasound surgery, and
      indicates that each sonication system must be carefully evaluated for potential
      thermal damage outside of the target volume prior to implementation in therapy.

PMID- 8134979
TI  - Acoustic properties of lesions generated with an ultrasound therapy system.
AB  - Methods for quantitative imaging of ultrasound propagation properties were
      applied to the examination of the acoustic appearance of lesions generated by
      high intensity focused ultrasound in excised pig livers. Single lesions, about 10
      mm maximum diameter by 30 mm long, were created in each of six liver specimens.
      Two dimensional images (32 by 32 points) of sound speed, mean attenuation
      coefficient (as a function of frequency in the range 3 to 8.5 MHz) and mean
      backscattering coefficient (5 to 8 MHz) were obtained in 7 mm thick sections of
      tissue, cut to include a cross-section through the lesion. Images of these
      properties, presented alongside surface photographs of the samples, provided a
      qualitative demonstration that attenuation coefficient was the most useful and
      backscattering coefficient was the least useful acoustic parameter for
      visualizing such lesions. Quantitatively the data demonstrated significant
      increases in attenuation coefficient and sound speed in lesioned liver relative
      to normal, whereas backscattering was shown not to change in a significant manner
      except when undissolved gas is the mechanism for increased acoustic scattering.
      Samples where gas was not fully removed following lesion production gave
      significant increases in backscattering at the lesion centre, but the shape and
      size of regions of high backscattering coefficient corresponded poorly with the
      shape and size of the lesions, unlike attenuation and sound speed for which such
      correspondence was good.

PMID- 8134981
TI  - Vesicoureteral reflux update: effect of prospective studies on current
      management.

PMID- 8134980
TI  - Characterization of extracorporeal ablation of normal and tumor-bearing liver
      tissue by high intensity focused ultrasound.
AB  - Treatment parameters of extracorporeal high intensity focused ultrasound (HIFU)
      were analysed in normal and tumor-bearing rabbit liver. HIFU was generated with a
      1 MHz transducer and energy was provided by a 7.5 kW power amplifier. In vivo
      experiments were conducted on 74 New Zealand rabbits. Normal rabbits and rabbits
      bearing an intrahepatic VX2 tumor were used. In group 1, spatial peak temporal
      peak (SPTP) intensities ranging from 1470 to 5500 W cm-2 and exposure times from
      0.5 to 5 s were tested at a constant depth in the liver; in group 2, the output
      power was adjusted as a function of the target depth in order to keep constant
      the focal in situ intensity in the liver; in group 3 (liver tumors), the focal in
      situ intensity was 1365 W cm-2 in eight rabbits and 500 W cm-2 in nine. In groups
      1, 2 and 3, rabbits were sacrificed 48 h after the treatment. Groups 4 and 5 were
      designated for analysis of the lesion in the normal liver 4 weeks after treatment
      at 1000 W cm-2 and 3000 W cm-2 SPTP intensities, respectively. In normal rabbits,
      the lesion volume increased with exposure time at constant intensity; there was a
      negative correlation between intensity and exposure time (group 1). When the
      output power was adjusted as a function of the path length, the lesion size was
      nearly constant (group 2). In VX2 rabbits, tumor destruction rates were
      significantly higher in rabbits treated at 500 W cm-2 than in rabbits treated at
      1365 W cm-2 (p < 0.05; group 3). As in the normal liver, the lesion volume
      increased with the exposure time at constant intensity. HIFU lesions treated at
      1000 w cm-2 (SPTP) healed as thin fibrous scars, and no severe complication
      occurred (group 4); at 3000 W cm-2 (SPTP), scars were larger and perforation of a
      neighbouring organ was seen in 7 of 11 rabbits (group 5).

PMID- 8134982
TI  - Xanthogranulomatous pyelonephritis: clinical findings and surgical
      considerations.
AB  - OBJECTIVE: Xanthogranulomatous pyelonephritis (XGP) is an uncommon but well
      characterized inflammatory process of the kidney. Few reports, however, have
      correlated preoperative radiographic features with findings at surgical
      exploration. We report our experience in the surgical management of XGP with
      emphasis on the use of computed tomography (CT) in the preoperative evaluation.
      METHODS: We retrospectively reviewed all medical records including radiographic
      materials of 27 patients with a pathologic diagnosis of XGP. In particular,
      preoperative CT features were analyzed to see if they correlated with surgical
      findings. RESULTS: A CT scan was performed in 23 of the 27 patients. Of these 23
      patients 20 (87%) were diagnosed with XGP based on the CT findings. CT accurately
      defined the extent of the perinephric inflammatory reaction, identifying 8
      patients with muscular extension, 3 with splenic involvement, 1 with extension
      into the colon, and 5 with encasement of the great vessels. In no case did CT
      underestimate the involvement of adjacent tissues. CONCLUSIONS: Although XGP is a
      rare disease, a careful preoperative evaluation can suggest its diagnosis. CT is
      particularly valuable in that it not only demonstrates characteristic renal
      findings, but also shows the extent of inflammation and extent into adjacent
      tissues. This will aid in surgical planning in choosing an approach that will
      provide adequate exposure and facilitate patient care.

PMID- 8134983
TI  - Renal cell carcinoma in New Zealand: a national survival study.
AB  - OBJECTIVE: To determine clinical and pathologic prognostic factors for renal cell
      carcinoma (RCC) using cases reported to a population-based cancer registry.
      METHODS: All cases of RCC reported to the New Zealand Cancer Registry between
      1976 and 1986 were retrieved and data analyzed to determine parameters of
      prognostic importance. RESULTS: In eleven years, 1,308 cases of RCC (66.7% males
      and 33.3% females) were reported to the New Zealand Cancer Registry. The age
      standardized incidence rate was 3.78 per 10(5) person-years and showed no
      significant trend over the period of the study. There was a significant
      difference in the age at presentation between the largest racial groups (Maori
      52.2 years; non-Maori 63.2 years), which is accounted for by increased
      predisposing risk factors among Maori. The five-year actuarial survival rate was
      42.4 percent with 63 percent of patients reported dead in follow-up to December
      1990. In the series, patient gender (female > male), tumor laterality (right >
      left), stage (intrarenal > localized > disseminated), grade (1 > 2 > 3 > 4), and
      treatment modality (surgery > nonsurgery) were found to be significant prognostic
      factors, although only tumor stage and treatment modality were of independent
      significance. Tumor laterality was of prognostic significance for Stage II
      (localized) surgically treated tumors only. CONCLUSIONS: The results of the study
      emphasize the paramount importance of tumor stage as a prognostic parameter for
      RCC. The prognostic significance of laterality for localized, surgically treated
      tumors suggests that radical nephrectomy is less likely to result in tumor
      clearance for left-sided RCC than for tumors on the right side.

PMID- 8134984
TI  - Unilateral renal papillectomy via laser or incisional techniques: chronic
      functional effects in the dog.
AB  - OBJECTIVE: To determine if selective renal papillectomy would impair urinary
      concentrating ability, thereby decreasing urinary calcium concentration. METHODS:
      Left papillectomy was performed in dogs using either incisional (n = 6) or
      Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (n = 5) techniques. Split renal
      function studies were then performed four months postoperatively to determine the
      effect on multiple parameters including inulin and para-aminohippurate (PAH)
      clearance, free water reabsorption, and calcium concentrations. Partially
      infarcted kidneys (n = 6) were evaluated in a similar fashion to determine the
      role of impaired glomerular filtration rate (GFR) in the observed concentrating
      defect occurring after papillectomy. RESULTS: Papillectomized kidneys
      demonstrated impaired free water reabsorption, resulting in a decreased urinary
      osmolality and an increased fractional excretion of water. Osmolar clearance
      [Na+] and Na+ excretion were unaffected by papillectomy, whereas [Ca++] was
      significantly reduced. While a slight defect in free water reabsorption existed
      following partial infarction, urinary osmolality was only minimally decreased,
      fractional excretion of water was unchanged, and Na+ excretion was decreased.
      CONCLUSIONS: The concentrating defect induced by papillectomy via either sharp
      excision or laser ablation is due to loss of medullary tissue and is greater than
      the defect resulting from impaired GFR, which is presumably due to decreased
      medullary solute delivery and increased flow of water in remaining nephrons.
      Since the physiologic consequences of papillectomy (formation of less
      concentrated urine with decreased [Ca++]) have potential clinical applicability,
      further study of this concept is warranted.

PMID- 8134985
TI  - Retrospective analysis of outcome in patients with nodal metastases from
      transitional cell carcinoma of lower urinary tract.
AB  - OBJECTIVE: To determine the outcome in patients with nodal metastases from
      transitional cell carcinoma (TCC) using currently available surgical and
      chemotherapeutic techniques. METHODS: A retrospective analysis of all patients
      with TCC of the lower urinary tract who underwent radical cystectomy or lymph
      node dissection at our institution since 1980 was performed. Thirty-one patients
      were identified who had documented pelvic lymph node metastases prior to or at
      the time of radical cystectomy. These patients' records were reviewed in-depth
      with regard to treatment approach, presenting features, and outcome. RESULTS:
      Outcome was poor despite the treatment approach taken, including whether or not
      chemotherapy was administered prior to or after cystectomy. Median survivals of
      patients receiving no chemotherapy, adjuvant chemotherapy, and neoadjuvant
      chemotherapy were 14.5, 9.5, and 15.0 months, respectively. Only 4 of 28 patients
      survived more than three years, and only one of these received chemotherapy.
      CONCLUSIONS: Survival of patients with lymph node metastases from transitional
      cell carcinoma remains poor despite aggressive surgical therapy and the use of
      adjuvant or neoadjuvant platinum-based chemotherapy.

PMID- 8134986
TI  - Effects of alpha-adrenergic agonist on neobladder water and electrolyte
      transport.
AB  - OBJECTIVE: Nocturnal urinary incontinence and nocturia are problematic for
      patients with continent neobladders. Clonidine, an alpha 2-adrenergic agonist,
      increases water absorption across rabbit ileum; human intestine contains a
      substantial density of alpha 2-adrenergic receptors. We studied the effect of
      neobladder clonidine instillation and catheterization (to reduce urine-bowel
      contact time) on nocturnal water and electrolyte reabsorption. METHODS: A total
      of 8 patients with Indiana neobladders constructed after radical cystectomy were
      studied at a mean of 11.3 months postoperatively under standardized diet and
      fluid intake. RESULTS: Topical clonidine or catheterization failed to alter
      nocturnal urine volume, free-water clearance, or absolute excretions of
      electrolytes in Indiana neobladders; however, the absolute excretion of urine
      urea nitrogen and osmoles was significantly increased in the catheterized urine
      collections compared with the baseline urine collections (paired t-test, p =
      0.0022 and 0.0091, respectively). CONCLUSIONS: Bowel comprising neobladders loses
      its capacity to significantly alter urinary electrolyte composition by prolonged
      contact, which may explain the rarity of significant acid-base disturbances in
      patients with continent neobladders. Unfortunately, topical clonidine does not
      diminish nocturnal urine volumes, but increased excretion of urea and osmoles
      with overnight neobladder catheterization may prove beneficial in patients who
      suffer azotemia or hyperosmolarity.

PMID- 8134987
TI  - Continuous versus intermittent flow irrigation in transurethral resection of the
      prostate.
AB  - OBJECTIVE: We compared fluid absorption, blood loss, and immediate postoperative
      complications in transurethral resection of the prostate (TURP) performed with
      the continuous flow and the intermittent flow irrigation techniques. We also
      studied pressure conditions under which fluid absorption occurs when continuous
      flow irrigation is used. METHODS: One experienced urologic surgeon performed TURP
      in 40 patients using suprapubic drainage of the bladder and in 40 other patients
      using the intermittent-filling technique. Fluid absorption was measured by the
      ethanol method every ten minutes. The intravesical pressure was recorded
      continuously in 23 of the patients with suprapubic drainage. RESULTS: Fluid
      absorption was more common when suprapubic drainage was used (P < 0.004). There
      were no differences in operating time, blood loss, postoperative complications,
      or in the period of hospitalization. Low-degree absorption occurred during minor
      elevations of the intravesical pressure, and massive fluid absorption was
      associated with pressures between 1.0 and 2.5 kPa (10 and 25 cm H2O).
      CONCLUSIONS: Continuous flow irrigation promoted fluid absorption, which occurred
      at lower pressures than commonly believed. With respect to other parameters, we
      found no superiority of one irrigating technique over the other.

PMID- 8134988
TI  - Early discharge of transurethral prostatectomy patients with an indwelling Foley
      catheter.
AB  - OBJECTIVE: To assess feasibility of early discharge of patients after
      transurethral resection of the prostate (TURP) with an indwelling Foley catheter.
      METHODS: A retrospective study comparing a planned early discharge group and a
      standard post-TURP group. Comprising the study group were 47 consecutive TURP
      patients treated with the intent to be discharged early with an indwelling Foley
      catheter. The comparative group included 50 consecutive patients with the
      standard post-TURP hospital course. RESULTS: Twenty-seven of 47 patients (57%) in
      the study group were discharged on postoperative day 1 and a total of 43 (91%)
      were released within two days. Mean length of stay was 1.7 days. Four patients
      (8.5%) had medical problems prolonging stay. There were eight emergency room
      visits secondary to catheter problems or failed voiding trials. In the
      comparative group of 50 consecutive patients the mean length of stay was 3.9
      days. Five of 50 patients (10%) had medical problems prolonging stay.
      CONCLUSIONS: Complications were similar in each group. No readmissions or serious
      morbidities were noted in the patients with shortened hospital stay. Early
      discharge of post-TURP patients is a safe, feasible, and cost-effective
      alternative.

PMID- 8134989
TI  - Postchemotherapeutic surgery for metastatic testicular germ cell tumors: results
      of extended primary chemotherapy and limited surgery.
AB  - OBJECTIVE: Postchemotherapy surgery has become an increasingly important
      treatment for residual masses in germ cell tumors of the testis. However, it is
      still a challenge to find the optimal combination of chemotherapy and surgery for
      better survival and cure rates with lowest morbidity. This study evaluated the
      effectiveness of extended chemotherapy followed by surgery resecting only the
      residual masses. METHODS: After an extended course (one or two additional courses
      after there is no decrease in tumor size and/or after the normalization of tumor
      markers) of combination chemotherapies with cisplatin-based regimens, 32 patients
      underwent surgery for metastatic germ cell tumors of the testis. Complete
      excision of radiologically determined residual masses and macroscopically
      suspicious neighboring nodes was performed rather than a conventional
      retroperitoneal lymph node dissection. RESULTS: Histopathologic examination of
      the resected specimens revealed teratoma in 17 (55%), fibrosis and/or necrosis in
      9 (26.5%), and active residual tumor in 8 (23.5%) of the patients. The patients
      with residual tumor have been treated with additional chemotherapy. In the follow
      up (mean, 28.5 months) 4 patients have relapsed, and 1 died. None of the patients
      with residual teratomas have shown relapse. Only 1 of the 32 patients has had
      retrograde ejaculation. CONCLUSIONS: A more conservative approach, such as
      excision of the residual masses after an extended course of chemotherapy, has
      given excellent results both in the outcome of the patients in the follow-up and
      in the rate of retrograde ejaculation. We therefore suggest that this approach
      would be a good alternative to nerve-sparing surgery following chemotherapy.

PMID- 8134990
TI  - Urologic complications of high-dose chemotherapy and bone marrow transplantation.
AB  - OBJECTIVE: This study reviews the incidence and management of cyclophosphamide
      induced hemorrhagic cystitis in a group of patients who received high-dose
      chemotherapy and bone marrow transplantation. METHODS: The records of 217
      consecutive patients undergoing bone marrow transplantation were reviewed. The
      incidence, degree, and management of hematuria in this group of pancytopenic and
      immunocompromised patients were recorded. RESULTS: Despite prophylaxis, cystitis
      developed in 58 of these 217 patients (27%). In 12 patients (6%) the cystitis was
      severe. These patients had gross hematuria, clot retention, and drop in
      hematocrit necessitating blood transfusion. These patients were managed with
      continuous bladder irrigation, alum irrigation, and when less aggressive approach
      was unsuccessful, with intravesical formalin instillation. Alum irrigation was
      used in 5 patients, and was successful in only 1 patient. Six patients required
      intravesical formalin instillation to control the hematuria. Formalin solution 2
      5% was instilled initially. When lower-concentration formalin failed, 5-10%
      formalin was used progressively. CONCLUSIONS: Patients with bone marrow
      transplantation in whom severe hemorrhagic cystitis develops should be managed
      aggressively early. Intravesical formalin appears to be the most effective
      regimen in controlling profuse, persistent hematuria.

PMID- 8134991
TI  - Urethroscopy and urethral cytology in men with external genital condyloma.
AB  - OBJECTIVE: To develop guidelines as to which asymptomatic male patients with
      genital human papillomavirus (HPV) infection need further evaluation of the
      urethra, we studied two screening methods: urethroscopy and voided urethral
      cytology. METHODS: In a four-year period, 135 asymptomatic men underwent complete
      screening for HPV infection. They were evaluated because of HPV-related genital
      disease in their female sex partners or visible genital lesions, or both.
      RESULTS: Of the 135 patients, 21 (16%) had no clinical, subclinical, cytologic,
      or urethroscopic evidence of disease, and 114 (84%) had biopsy-proven HPV
      infection. Of these 114 patients, only 14 (12.3%) had intraurethral condyloma.
      All of these 14 patients had current or historical evidence of meatal or
      perimeatal "sentinel" lesions. They constituted 29.8 percent of 47 such patients
      with sentinel lesions. In 5 patients (4%), results of voided urine cytology were
      positive for condyloma cells, but only 1 of these had visible intraurethral
      disease. Of the 14 patients with urethral disease, only 1 (7%) had positive
      results of urine cytology. CONCLUSIONS: These observations suggest that any
      asymptomatic male patient undergoing screening for condyloma acuminatum who has a
      history of or demonstrable subclinical or grossly visible perimeatal or meatal
      HPV infection should undergo urethroscopy and that voided urine cytology is not a
      reliable or cost-effective test for the detection of visible intraurethral
      disease.

PMID- 8134992
TI  - Prospective comparison of topical minoxidil to vacuum constriction device and
      intracorporeal papaverine injection in treatment of erectile dysfunction due to
      spinal cord injury.
AB  - OBJECTIVE: To compare the effectiveness of topically applied 2% minoxidil to that
      of intracorporeal injection therapy and vacuum constriction devices for the
      treatment of erectile dysfunction in the spinal cord injured (SCI) male. METHODS:
      Eighteen SCI men, aged nineteen to sixty-five years (median age, 29), and level
      of injury C7 to L3 (15 thoracic level) were prospectively evaluated. All patients
      were able to achieve only a poorly sustained reflex erection that was inadequate
      for satisfactory intercourse. No patient had suffered erectile dysfunction prior
      to his SCI. In each patient, 1 mL of a 2% minoxidil solution was applied as an
      aerosol spray to the glans penis. The erectile response was compared to that
      obtained with a vacuum constriction device (VCD) and intracorporeal papaverine
      injection. In each case, the subjective assessment by both the patient and the
      physician, as well as objective results of penile base rigidity as measured by
      the RigiScan DT Monitor Device, were recorded. RESULTS: Papaverine increased
      rigidity at the base of the penis by a median 77 percent (range, 30-100%). The
      VCD increased rigidity by a median 57 percent (range, 30-80%). Minoxidil induced
      no change in rigidity (range, 0-15%). No complications were observed for any
      method of inducing tumescence. CONCLUSIONS: Papaverine and VCD proved to be
      effective means of establishing penile erection in male SCI patients. Both
      subjective and objective erectile responses to minoxidil were poor. Nevertheless,
      the principle of topical therapy is an attractive alternative to existing
      modalities. Further investigation is warranted.

PMID- 8134993
TI  - Male pseudohermaphroditism: factors determining the gender of rearing in Saudi
      Arabia.
AB  - OBJECTIVE: Experience with male pseudohermaphrodites at King Fahd Hospital of
      King Faisal University, Al-Khobar, Saudi Arabia from 1981 to 1991 was reviewed to
      ascertain the factors determining the gender of rearing. METHODS: The records of
      14 patients consisting of 6 prepubertal and 8 postpubertal patients were studied.
      None of the patients had any prior evaluation or treatment, since their gender
      assignment at birth was carried out by midwives in rural communities. The males
      presented to our hospital with ambiguous genitalia: small phallus, bifid scrotum,
      perineoscrotal hypospadias, and undescended testes (UDT). Most of those raised as
      females presented in the postpubertal period seeking remedy for deep voice,
      excessive musculature, facial hair, erection of the phallus, ejaculation,
      inappropriate attraction to the female sex, and primary amenorrhea. As their male
      genotype became determined, all the patients and/or their parents, with the
      exception of one, insisted on appropriate reconstructive surgery to the male
      gender. This report focuses primarily on 11 patients assigned a female gender at
      birth, 10 of whom insisted on a gender change. RESULTS: Most adolescents and
      adults still complained of small penises after reconstructive surgery, but
      cherished their male role. CONCLUSIONS: The male genotype is a more important
      factor than phallic adequacy in determining the gender of rearing in the Kingdom
      of Saudi Arabia, an observation attributable to the financial, social, and
      cultural benefits that the male gender confers in Saudi society.

PMID- 8134994
TI  - A unique fasciocutaneous flap for posterior urethral repair.
AB  - The anatomic restrictions produced by male to female gender reassignment surgery
      necessitated a new surgical solution to treat a traumatic posterior urethral
      stricture. Aesthetic considerations were of paramount importance to the patient.
      A unique use of the pudendal thigh fasciocutaneous flap is presented which
      satisfied the reconstructive needs of well-vascularized tissue for reconstruction
      of the posterior urethral segment, and addressed the patient's aesthetic
      concerns. Correction of the posterior urethral stricture was successful, and the
      flap donor site inconspicuous. This procedure has not been described previously
      for urethral reconstruction and is an additional regional source of vascularized
      tissue for urethral repair.

PMID- 8134995
TI  - Acquired crossed renal ectopia secondary to a giant renal cyst.
AB  - We report a case of contralateral renal displacement due to a giant ipsilateral
      renal cyst. Drainage and partial excision of the cyst was followed by return of
      the kidney and liver to their normal positions. Incidentally, a small focus of
      renal cell carcinoma was found after pathologic examination of the cyst wall. The
      relevant literature is reviewed.

PMID- 8134996
TI  - Prenatal diagnosis of cloacal malformation.
AB  - Cloacal malformation is a rare abnormality, occurring only in females and
      characterized by a direct communication between the gastrointestinal, urinary,
      and genital structures resulting in a single perineal opening. We report 2 cases
      of prenatal diagnosis of this condition with a varied ultrasonic appearance
      including fetal ascites, cystic retrovesical mass, ambiguous genitalia,
      nonvisualization of the bladder, and oligohydramnios.

PMID- 8134997
TI  - Carcinosarcoma of urinary bladder: report of 5 cases with immunohistologic study.
AB  - We studied 5 cases of carcinosarcoma of the urinary bladder. Immunoperoxidase
      studies were performed to identify the nature of the tumor and to establish the
      diagnosis. We suggest that these tumors represent a transition of epithelial to
      mesenchymal malignancy. Three of our patients had a history of radiation therapy
      prior to development of carcinosarcoma; of which 2 had a long interval between
      exposure to radiation and tumor development. Radiation is a risk factor for
      endometrial carcinosarcoma, and in this report we strongly suggest such an
      association for the urinary bladder.

PMID- 8134998
TI  - Signet ring cell adenocarcinoma of prostate.
AB  - Primary signet ring cell adenocarcinoma of the prostate is a rare malignancy with
      a total of 13 cases reported to date in the English literature. We report a very
      unusual case of signet ring adenocarcinoma of the prostate occurring in a patient
      who presented initially with irritative voiding symptoms and a bladder mass.
      Results of immunohistochemical, flow cytometric, and cytogenetic analyses of the
      tumor are presented.

PMID- 8134999
TI  - Corporeal fibrosis as a result of priapism prohibiting function of self-contained
      inflatable penile prosthesis.
AB  - Corporeal fibrosis and erectile impotence are known sequelae of priapism.
      Fibrosis following priapism may make subsequent placement of a penile prosthesis,
      especially inflatable devices, difficult or impossible. A case is described in
      which a self-contained inflatable prosthesis (Dynaflex) was successfully placed
      to treat impotence resulting from idiopathic priapism. However, fibrosis of the
      distal tunica albuginea of the corpora cavernosa rendered them noncompressible,
      and thus precluded inflation of the device with its distally placed pump
      mechanism. This anatomic problem is added to the list of potential
      contraindications to placement of self-contained inflatable penile prostheses,
      and the advisability of having patients who desire such a prosthesis also choose
      a secondary prosthesis type is emphasized.

PMID- 8135000
TI  - Endoscopic management of persistent lymphocele following laparoscopic pelvic
      lymphadenectomy.
AB  - OBJECTIVE: To report an alternative form of management of a persistent lymphocele
      that was unresponsive to percutaneous drainage and ethanol sclerotherapy.
      METHODS: Herein is described the technique of dilating the previously established
      percutaneous drainage tract to facilitate insertion of a flexible ureteroscope.
      Through this instrument electrosurgical fulguration of the lymphocele cavity was
      performed. RESULTS: The patient had complete resolution of the lymphocele cavity
      on computed tomography (CT) scan and remains asymptomatic at six months of follow
      up. CONCLUSIONS: Flexible ureteroscopic access and fulguration of a lymphocele
      proved to be a safe and effective method of obliterating the lymphocele cavity.

PMID- 8135001
TI  - Misleading interpretation of results from a small study.

PMID- 8135002
TI  - Management of acute ureteral obstruction in pregnancy utilizing ultrasound-guided
      placement of ureteral stents.

PMID- 8135003
TI  - Combined treatment with concentrated essential fatty acids and prednisolone in
      the management of canine atopy.
AB  - Eleven perennially affected atopic dogs which had previously responded poorly to
      dietary supplementation with a combination of evening primrose oil and fish oil
      were studied to determine whether a concentrated essential fatty acid supplement
      containing gammalinolenic acid and eicosapentaenoic acid would reduce their
      prednisolone requirements. The prednisolone dose required for satisfactory
      control of the dogs' clinical signs was reduced in eight of the 11 cases when
      assessed after 12 weeks of supplementation, but there were no significant
      differences in mean clinical scores during the same period. The mean plasma
      phospholipid linoleic acid concentrations after eight and 12 weeks of
      supplementation were significantly lower than the initial mean value but there
      were no significant differences in the mean plasma phospholipid concentrations of
      dihomogammalinolenic acid, arachidonic acid and eicosapentaenoic acid.

PMID- 8135004
TI  - Haptoglobin as an indicator of infection in sheep.
AB  - An automated method for the estimation of the acute phase protein haptoglobin was
      developed and used to compare the blood haptoglobin concentrations of 42 sheep
      examined post mortem with other haematological findings in infectious and non
      infectious conditions. Haptoglobin was also assayed in 863 sheep from nine
      apparently normal flocks; of these sheep seven per cent had significantly raised
      haptoglobin levels. The studies showed that haptoglobin was useful as a marker
      for the presence of bacterial infection in sheep, and was more sensitive,
      specific and efficient and less likely to give false positive and negative
      results than a haematological examination.

PMID- 8135005
TI  - Ultrasonography of the ureterovesicular junction in the dog: a preliminary
      report.
AB  - Contrast radiography followed by ultrasonography of the urinary bladder was
      performed on 10 incontinent dogs. The ureterovesicular junctions and ureteral
      jets were identified by ultrasonography in all the dogs except one that had a
      caudally displaced bladder. An ectopic ureter in one dog was diagnosed by
      ultrasonography on the basis of the absence of a ureteral jet on the affected
      side, and the direct identification of the ureter passing caudal to the bladder
      neck. Ultrasonography appears to be a simple, repeatable test for identifying the
      distal ureters.

PMID- 8135006
TI  - Management of urinary incontinence in five bitches with incompetence of the
      urethral sphincter mechanism by colposuspension and a modified sling
      urethroplasty.
AB  - Urinary incontinence due to incompetence of the urethral sphincter mechanism was
      diagnosed in five neutered female dogs. After poor clinical responses to medical
      treatment, the five bitches were managed by a combination of colposuspension and
      sling urethroplasty. No major complications developed, although three bitches
      voided small volumes of urine more frequently for the first few days after
      surgery. The response to surgery was considered excellent in the two dogs which
      became continent and poor in the three which did not. In one of the dogs which
      responded poorly, the incontinence resolved after a revision of the
      colposuspension part of the procedure, and in the other two the incontinence
      became more responsive to medical management. The addition of a sling
      urethroplasty to colposuspension appeared to have little beneficial effect.

PMID- 8135007
TI  - An unusual outbreak of Streptococcus bovis septicaemia in racing pigeons (Columba
      livia).
AB  - In December 1991, an outbreak of Streptococcus bovis septicaemia occurred in a
      Belgian pigeon loft where 25 male and 25 female racing pigeons were housed. The
      main clinical signs included inability to fly and poor breeding results. None of
      the female pigeons and only one male pigeon was able to fly. Nine affected
      pigeons were necropsied. Histologically a tenosynovitis of the tendon of the deep
      pectoral muscle was observed in most of them and S bovis was isolated from the
      canalis triosseus or the shoulder joints of five of the nine pigeons. The pigeons
      were successfully treated with ampicillin administered in the drinking water for
      seven days.

PMID- 8135008
TI  - Factors affecting the incidence of bruising in lambs arriving at one
      slaughterhouse.

PMID- 8135009
TI  - Welfare and organic farming.

PMID- 8135011
TI  - Live strandings.

PMID- 8135010
TI  - Welfare and organic farming.

PMID- 8135012
TI  - Neospora-associated bovine abortion in Northern Ireland.

PMID- 8135013
TI  - Prescribing for racing greyhounds.

PMID- 8135014
TI  - Control of rabies in foxes: what are the appropriate measures?
AB  - Until recent years, the depopulation of reservoir species was the only feasible
      measure to break the transmission chain of rabies in wildlife. In Europe at the
      beginning of this century, when applied with compulsory muzzling and restrictions
      on movement, dog depopulation was shown to be effective before any large scale
      vaccination of dogs. Some examples of the success of the application of
      depopulation measures on wild carnivores in the past are described. But in the
      case of enzootics of rabies in the fox, the control measures applied to fox
      populations sometimes decreased the prevalence or postponed the invasion of an
      area but did not free or protect an area permanently. Some examples taken from
      France illustrate the difficulties of drawing clear conclusions from the results
      of control measures. Conversely, the oral vaccination of foxes was demonstrably
      successful in preventing the spread of rabies. However, mathematical modelling,
      historical considerations and first observations in areas in which foxes have
      been vaccinated strongly suggest that the 'traditional' methods of controlling
      fox populations, at least by hunting, should not be restricted because they
      complement the effects of vaccination.

PMID- 8135015
TI  - Interaction between Streptococcus suis serotype 2 and porcine reproductive and
      respiratory syndrome virus in specific pathogen-free piglets.
AB  - Secondary specific pathogen-free (sSPF) piglets were inoculated intranasally with
      Streptococcus suis serotype 2 alone, porcine reproductive and respiratory
      syndrome virus (PRRSV) alone, or with PRRSV followed by S suis. Uninfected
      piglets were used as controls. Pigs inoculated with PRRSV (ATCC VR-2332) followed
      by challenge with a virulent strain (87555) of S suis serotype 2 developed
      clinical signs, suppurative meningitis and large numbers of S suis in their
      tissues, including the brain and meninges. Pigs inoculated with PRRSV alone, S
      suis (87555) alone, or with PRRSV and the DH5 strain of S suis serotype 2
      (lacking a protein associated with virulence) and the uninfected piglets did not
      develop clinical signs or lesions or have large numbers of bacteria in their
      tissues. The results suggest that PRRSV predisposes sSPF pigs to infection and
      disease caused by virulent S suis serotype 2. Co-infection of piglets with PRRSV
      and a virulent strain of S suis may provide a useful model for the study of S
      suis septicaemia and meningitis.

PMID- 8135016
TI  - Horner's syndrome in an African spotted eagle owl (Bubo africanus).
AB  - An unilateral ptosis in an African spotted eagle own was ameliorated by topical
      treatment with phenylephrine, strongly suggesting a diagnosis of Horner's
      syndrome, the first recorded case of this syndrome in a bird.

PMID- 8135017
TI  - Haemangiosarcoma associated with leishmaniasis in three dogs.

PMID- 8135018
TI  - Hyaluronidase and chondroitinase activity of Pasteurella multocida serotype B:2
      involved in hemorrhagic septicaemia.

PMID- 8135019
TI  - Update on equine influenza.

PMID- 8135020
TI  - Welfare and organic farming.

PMID- 8135021
TI  - Eperythrozoon suis in weaned pigs.

PMID- 8135022
TI  - Effects of Psoroptes ovis on lamb carcases.

PMID- 8135023
TI  - Investigation of nonresponse bias: Hispanic Health and Nutrition Examination
      Survey.
AB  - This report presents an investigation of potential nonresponse bias in the
      Hispanic Health and Nutrition Examination Survey (HHANES) conducted during the
      period 1982-84. Data from a household and medical history interview were used to
      investigate factors related to examination status. The study includes a
      comparison of data for examinees in HHANES with data from interviewees in the
      National Health Interview Survey during 1982, 1983, and 1984.

PMID- 8135024
TI  - Evaluation of National Health Interview Survey diagnostic reporting.
AB  - This report presents the results of a study of the reporting of chronic
      conditions in the National Health Interview Survey. The analysis compares the
      reporting of certain chronic conditions by household interview respondents
      against the presence of these conditions in medical records, examining the
      differences in agreement across conditions and across respondent characteristics.

PMID- 8135025
TI  - [Complications of routine intensive care interventions].
AB  - The frequent use of invasive procedures for diagnosis, monitoring, and treatment
      in intensive care units engenders often underestimated dangers due to human error
      or complications which are to some extent inherent. A brief survey is given of
      adverse events in connection with central venous catheters, Swan-Ganz catheters,
      arterial lines, endotracheal intubation, gastric tubes, and cardiopulmonary
      resuscitation. Strategies to reduce the risks are outlined. Documentation of
      adverse events and near misses, along with an analysis of their causes constitute
      indispensable elements of quality control in intensive care medicine. Policies to
      avoid adverse events, as well as guidelines to recognize and treat them promptly
      should be regularly scrutinized.

PMID- 8135026
TI  - Oropharyngeal decontamination with gentamicin for long-term ventilated patients
      on stress ulcer prophylaxis with sucralfate?
AB  - The incidence of nosocomial pneumonia in long-term ventilated patients has been
      reduced by stress ulcer prophylaxis with sucralfate. In a double-blind trial we
      studied whether gentamicin administered topically to the oropharynx (OPG) had
      additional clinical benefits in these patients. 67 critically ill adult patients
      fulfilled entry criteria for > or = 5 days on ventilation. The OPG group received
      40 mg gentamicin, the control group received 5% dextrose topically administered
      to the oropharynx 4 times a day. During OPG, pharyngeal colonization rate (21 vs
      44%) and tracheal secretion colonization rate (12 vs 41%) were significantly
      lower than during placebo (p < 0.05). Despite these differences nosocomial
      pneumonia rate (3 vs 12%), duration of mechanical ventilation [15.8 +/- 11.1 vs
      19.9 +/- 37.5 days (means +/- SD)] and mortality (27 vs 41%) were not
      significantly affected by OPG. Moreover, 13 of 15 bacteria (87%) that occurred
      during OPG were resistant to gentamicin. Despite its reduction of bacterial
      colonization rates of pharyngeal and tracheal secretions, OPG did not seem to
      offer additional clinical benefits in long-term mechanically ventilated patients
      on stress ulcer prophylaxis with sucralfate.

PMID- 8135027
TI  - [Resistance spectrum of staphylococci at the Vienna general hospital (July to
      December 1991)].
AB  - This study describes the antibiotic resistance of 1961 staphylococcal strains
      that were isolated at the University Hospital of Vienna from July to December
      1991. Staphylococcus aureus (SA) represented 43.2%; coagulase-negative (CNS)
      staphylococci 56.8%, three quarters of which were Staphylococcus epidermidis.
      Excepting netilmicin, the proportion of resistant strains to all antibiotics was
      higher with CNS than SA. Methicillin resistance (M(r)) was found in 11.8% of SA
      and 30.3% of CNS. Borderline oxacillin resistance (BOR) was noted in 7.4% of SA
      and 32.5% of CNS. It is important to note that severe or generalized infections
      due to M(r) staphylococci should be treated with glycopeptide antibiotics such as
      vancomycin or teicoplanin from the very beginning, whereas chemotherapy of those
      with BOR strains may also be carried out with beta lactamase-stable beta lactam
      antibiotics. Comparing the results of this study with those of the first half of
      1991, the respective proportion of M(r) staphylococci was significantly lower
      than 23.6% for SA and 47.6% for CNS recorded then. As compared with the foregoing
      period, however, these strains demonstrated increased resistance frequencies to
      gentamicin (from 81.3 to 90%), amikacin (from 35.4 to 69%), netilmicin (35.4 to
      55%), and ciprofloxacin (56.2 to 64%). This is taken as an indication for the
      epidemic spread of a clone of resistant strains.

PMID- 8135028
TI  - [Carbamazepine poisoning: protracted course with development of intestinal atony
      and hepatic toxicity].
AB  - A 43 year-old female patient with a history of manic-depressive illness and
      prophylactic carbamazepine (CBZ) medication ingested a potentially lethal
      overdose of 20 g of the substance. Neurotoxic symptoms reached full intensity
      after about 24 hours. Subsequently, the patient developed a gastrointestinal
      atony, which proved to be refractory to treatment for several days. Moreover,
      there was an increase of bilirubin. Parallel to this we observed the persistence
      and even intermittent re-increase--of toxic serum CBZ concentrations for one week
      with corresponding protracted clinical symptomatology.

PMID- 8135029
TI  - [Method for determination of diffusion capacity in clinical use and research:
      comparison of "single breath CO" and the "CO intra breath" method].

PMID- 8135030
TI  - ["Small volume resuscitation"--does it open new possibilities in the treatment of
      hypovolemic shock?].
AB  - Hypertonic-hyperoncotic solutions are a supplementation to conventional fluid
      regimens in the management of hypovolemia due to trauma, hemorrhage and shock. In
      this review the possible modes of action of these solutions are discussed and
      their efficacy both in experimental and clinical settings is presented. Possible
      side effects, such as hypernatremia and possible problems in the presence of
      increased intracranial pressure, following administration of hypertonic
      hyperoncotic solutions are discussed, as well as the reaction of normovolemic
      patients to such infusions.

PMID- 8135031
TI  - [Principles of the pharmacokinetics and pharmacodynamics of calcium antagonists].
AB  - Today calcium antagonists (Ca-antagonists) are widely used agents in the
      management of various diseases of the circulatory system. More than 20 years ago
      the Ca-antagonists of the so-called 1st generation (Verapamil, Diltiazem,
      Nifedipine) were introduced for treatment of angina pectoris and later of
      essential hypertension. In the last decade an increasing number of agents
      structurally related to dihydropyridines were developed for the treatment of
      hypertension and/or coronary heart disease or cerebral disorders; the main target
      was to reduce side effects and to guarantee once or at least twice daily
      administration. Therefore the Ca-antagonists of the so-called 2nd generation
      (e.g. Amlodipine, Felodipine, Isradipine, Nitrendipine, Nicardipine, Nimodipine,
      Nisoldipine) tend to longer elimination-half-lives; Amlodipin is an exception
      with an elimination-half-life of 30 hours on the average. Apart from elimination
      rates, however, the biopharmaceutical and pharmacokinetic characteristics of all
      Ca-antagonists are similar: they are highly cleared drugs and are relatively
      highly protein bound. As they are subject to significant hepatic first-pass
      metabolism old age and hepatic disease will increase their plasma-concentrations.
      Renal impairment affects little their pharmacokinetics since the fraction
      eliminated unchanged by the kidneys is small. For most agents, plasma
      concentration-response relationships have been described. With exception of
      nicardipine a linear pharmacokinetic in all Ca-antagonists was demonstrated.
      Drugs and food affecting hepatic blood flow and drug metabolising capacity have
      predictable interaction potential. With regard to the acute pharmacodynamic
      effects the Ca-antagonists show similar qualitative effects, though there are
      quantitative differences. Orally administered dihydropyridine-derivatives induce
      acute hypotensive effects, whereas the other compounds show clinically relevant
      hypotensive effects only when administered chronically per os or less pronounced
      when given as intravenous infusion.

PMID- 8135032
TI  - [Calcium antagonists and coronary heart disease. An overview].
AB  - Calcium antagonists (Ca-antagonists) have been used for 2 decades in the
      treatment of coronary heart disease. Their use has initially been promoted with
      variant angina, but soon has expanded to all forms of coronary heart disease,
      entailing both stable and instable angina. Based on promising experimental
      findings, these drugs have also been given in myocardial infarction, however,
      with disappointing results. The same was true for secondary prevention. The basic
      principle underlying Ca-antagonistic therapy of ischaemic heart disease is the
      improvement of myocardial oxygen balance. On the one hand, Ca-antagonists (in
      particular verapamil and diltiazem) reduce myocardial oxygen demand via negative
      inotropic and chronotropic action--on the other hand, the afterload is reduced by
      peripheral vasodilation. In addition, coronary dilation improves oxygen delivery,
      especially during exercise. Ca-antagonists inhibit transsarcolemmal Ca-influx,
      thus preventing deleterious myocardial Ca-overload as seen during ischaemia and
      atherosclerosis. Indeed, recent human studies have proven a preventive effect of
      Ca-blockers against atherosclerosis.

PMID- 8135033
TI  - [Calcium antagonists in therapy of arterial hypertension].
AB  - Calcium antagonists reduce the peripheral vascular resistance thus lowering an
      elevated blood pressure. Due to their properties they are regarded as basic
      antihypertensiva. They do not affect metabolism, cause a regression of left
      ventricular hypertrophy and improve the vascular compliance. Serious side effects
      are extremely rare. Because of their effects they are especially suitable for the
      therapy of arterial hypertension with certain attendant and resultant diseases of
      high blood pressure and with the existence of certain demographic factors like
      age and race.

PMID- 8135034
TI  - [Calcium channel blockers in therapy of neurologic diseases].
AB  - The clinical use of calcium antagonists (Ca-antagonists) in neurological diseases
      focuses on 2 main therapeutic fields: (a) For the therapy of migraine flunarizine
      is the first choice therapy and nimodipine is a second line treatment. With
      verapamil cluster headache can be treated successfully, flunarizine shows less
      impressive clinical efficacy. The therapy with flunarizine may be restricted due
      to the incidence of extrapyramidal disturbances and depressions as known side
      effects. (b) The therapy of clinical conditions after subarachnoidal bleeding
      with nimodipine is well established. In the therapy of acute cerebral ischemia
      the therapeutic efficacy of nimodipine administered orally is not therapeutically
      proved until now; the intravenous administration of nimodipine offers the risk of
      acute hypotensive reactions. At present the usefulness of the administration of
      ca-antagonists in the so-called cerebrovascular insufficiency or dementia and
      various others cerebral disorders with vertigo could not be demonstrated.

PMID- 8135035
TI  - [Calcium antagonists in pregnancy as an antihypertensive and tocolytic agent].
AB  - In pregnancy calcium antagonism is of great importance. The uterus-relaxing
      properties of verapamil are well known, diltiazem shows an excellent tokolytic
      efficacy and is also effective as hypotensive in pregnancy-induced hypotension.
      In contrast to verapamil and diltiazem the dihydropyridines were not clinically
      successful as tokolytic or hypotensive in pregnancy. Magnesium is a therapy of
      first choice in the EPH-gestosis.

PMID- 8135036
TI  - [Calcium antagonists as amplifiers of the mutagenicity of cytostatic drugs].
AB  - Some calcium antagonists enhance synergistically the mutagenic efficiency of
      cytostatics. The results so far obtained concerning this phenomenon are described
      and discussed: (1) chromosome aberrations induced (in vitro) in human lymphocytes
      (cytostatics; bleomycin and peplomycin; calcium antagonists: verapamil and
      fendiline), (2) chromosome and chromatid aberrations induced (in vitro) in
      Chinese hamster ovary (CHO) cells (cytostatic: mitomycin C; calcium antagonist:
      verapamil), (3) gene mutations induced in the bacterium Salmonella typhimurium
      (cytostatics: mainly various anilinoacridine drugs; calcium antagonist:
      verapamil). In all 3 studies neither verapamil nor fendiline proved to be
      mutagenic when applied alone. The "comutagenicity" of calcium antagonists is
      compared with the enhancement of the cytotoxic (cell killing) efficiency of
      cytostatics by calcium antagonists. Both phenomena--potentiation of mutagenicity
      and of cytotoxicity--are interpreted on the basis of the "accumulation
      hypothesis". According to this hypothesis those calcium antagonists would enhance
      the mutagenic and cytotoxic efficiency of the cytostatics by inhibiting their
      extrusion from the cell. Consequently, the cytostatics would be accumulated in
      the cell and this would increase their mutagenic and cytotoxic efficiency. Since
      not all calcium antagonists investigated so far enhance the mutagenicity and
      cytotoxicity of cytostatics, this potentiation seems not to be caused by their
      calcium antagonistic action per se. Molecular, evolutionary, and medical aspects
      of the "accumulation hypothesis" are shortly discussed.

PMID- 8135037
TI  - Disposition of stiripentol in the pregnant and non-pregnant female rat.
AB  - 1. The disposition of stiripentol labelled with 14C and 3H on two positions has
      been studied in the pregnant and non-pregnant female rat after p.o.
      administration of a 200 mg/kg dose. 2. For both labelled species radioactivity
      was eliminated mainly in the faeces (69% within 72 h). Urinary excretion was
      rather low (22% within 72 h). No significant difference was found between the
      disposition of the two labelled species. 3. For both labelled species
      concentrations of radioactivity reached a plateau in the plasma and tissues
      between 1 and 6 h after administration. The liver, fat, mammary gland and adrenal
      gland were the most extensively-labelled organs. The affinity for the mammary
      gland was significantly greater in pregnant rats and for the adrenal gland was
      significantly greater in the non-pregnant rats. The fact that the concentration
      in the placenta was higher than in the foetus demonstrated that this membrane
      acts as a barrier for the penetration of the drug in the amniotic fluid. 4.
      Chromatographic analysis of the faeces and urine showed that an important portion
      of the dose remained unabsorbed through the gastrointestinal tract. The absorbed
      fraction undergoes an extensive first-pass metabolism involving mainly the
      oxidative cleavage of the methylenedioxy ring. Comparison with the results of
      other work conducted on the non-pregnant rat demonstrated that pregnancy did not
      affect the disposition and metabolic process.

PMID- 8135038
TI  - Pharmacokinetic studies of diosmin and diosmetin in perfused rat liver.
AB  - 1. The kinetics and metabolism of diosmin and diosmetin were investigated in the
      isolated perfused rat liver in order to assess the role of the liver. 2.
      Diosmetin and especially diosmin disappeared quickly from the perfusion medium.
      3. Both flavonoids were rapidly metabolized and diosmetin was partly excreted in
      bile as the glucuronide and sulphate and diosmin was partly excreted in bile as
      such and as the glucuronide conjugate. 4. Diosmin and diosmetin did not appear to
      affect various parameters of liver function.

PMID- 8135039
TI  - Relationship between hydrocarbon structure and induction of P450: effects on
      protein levels and enzyme activities.
AB  - 1. Treatment of male rat with the small aromatic hydrocarbons, benzene, toluene,
      ethylbenzene, n-propylbenzene, m-xylene, and p-xylene increased several P450
      dependent activities, with ethylbenzene, m-xylene, and n-propylbenzene producing
      the greatest response. Hydrocarbon treatment differentially affected toluene
      metabolism, producing a response dependent on the metabolite monitored. In
      untreated rats, benzyl alcohol was the major hydroxylation product of toluene
      metabolism, comprising > 99% of the total metabolites formed. Hydrocarbon
      treatment increased the overall rate of toluene metabolism by dramatically
      increasing the amount of aromatic hydroxylation. Ethylbenzene, n-propylbenzene
      and m-xylene were the most effective inducers of aromatic hydroxylation of
      toluene. In contrast, production of the major toluene metabolite benzyl alcohol
      was increased only after treatment with m-xylene. 2. P450 2B1/2B2 levels were
      induced by each of the hydrocarbons examined, with the magnitude of induction
      increasing with increasing hydrocarbon size. P450 1A1 was also induced after
      hydrocarbon exposure; however, the degree of induction was smaller than that
      observed for P450 2B1/2B2. P450 2C11 levels were suppressed after treatment with
      benzene, ethylbenzene and n-propylbenzene. 3. Taken together these results
      display two induction patterns. The first generally corresponds to changes in the
      P450 2B subfamily, where activities (e.g. the aromatic hydroxylations of toluene)
      were most effectively induced by ethylbenzene, n-propylbenzene and m-xylene. In
      the second, induction was observed only after m-xylene treatment, a pattern that
      was found when the metabolism of the substrate was catalysed by both the P450 2B
      subfamily and P450 2C11. Hydrocarbons that both induced P450 2B1/2B2 and
      suppressed P450 2C11 (such as ethylbenzene and n-propylbenzene) showed little
      change in activities catalysed by both isozymes (e.g. aliphatic hydroxylation of
      toluene, and aniline hydroxylation); however, m-xylene treatment led to elevated
      P450 2B1/2B2 levels without significantly suppressing P450 2C11. m-Xylene
      produced significant increases in activities efficiently catalysed by both
      isozymes. Therefore, the unique induction pattern observed after m-xylene
      treatment can be accounted for by induction of P450 2B1/2B2 without concomitant
      suppression of P450 2C11.

PMID- 8135040
TI  - Metabolism of a tetrahydroaminoacridine derivative (SM-10888) in rat: structural
      analysis of an N-glucuronide of SM-10888 and an O-glucuronide of hydroxylated SM
      10888 by FAB-MS/MS.
AB  - 1. The metabolism of 9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine
      citrate (SM-10888), a cholinesterase inhibitor was studied in rat. 2. The phase I
      metabolite (designated M3) was isolated from urine and identified as 1
      hydroxylated SM-10888 by 1H-n.m.r. and EI-MS. 3. Two glucuronides (designated SMG
      and M3G) were isolated from bile and urine and their structures examined by FAB
      MS/MS and beta-glucuronidase hydrolysis. 4. FAB-mass spectra of SMG and M3G
      showed molecular ions ([M+H]+) at m/z 405 and 421, respectively. In their
      daughter spectra, fragment ions of aglycones (SM-10888 and M3), generated by the
      loss of glucuronic acid (176 amu) were observed. The daughter spectra of these
      aglycones were essentially similar to those of the corresponding synthetic
      standards. 5. SMG was hydrolysed non-enzymically at pH 5 as is often the case
      with N-glucuronides of arylamines. M3G could be hydrolysed by beta-glucuronidase
      but proved stable at pH 5. 6. From these results, SMG and M3G were concluded to
      be the N-glucuronide of SM-10888 and the O-glucuronide of M3, respectively.

PMID- 8135041
TI  - Metabolism of caffeine and theophylline in rats with malaria and endotoxin
      induced fever.
AB  - 1. The effects of malaria infection due to Plasmodium berghei and Escherichia
      coli endotoxin-induced fever on the metabolism of orally-administered caffeine
      (CA: 10 mg/kg) to its primary metabolites (theobromine (TB), paraxanthine (PX)
      and theophylline (TH)) were studied in 5-week-old male Wistar rats (n = 5 for
      each treatment). In separate experiments, the effects of malaria and endotoxin
      induced fever on the clearance of i.v.-administered theophylline (TH; 15 mg/kg)
      were studied in another group of rats. 2. The ratios of CA to the three primary
      metabolites (TB/CA, PX/CA, PH/CA) determined in a single plasma sample obtained 3
      h after CA administration were significantly reduced (p < 0.05) both by malaria
      and fever compared with control (saline) treatment. The clearance of TH
      determined from the concentration of TH in a single plasma sample obtained 6 h
      after TH administration was significantly reduced (p < 0.05) by fever but not
      malaria (4.0 +/- 0.7 ml/min/kg in controls; 4.2 +/- 0.5 in malaria; 2.4 +/- 0.4
      in fever). 3. These results suggest that malaria and fever have different effects
      on CA and TH metabolism in vivo, probably as a result of different effects on the
      hepatic isozymes involved.

PMID- 8135042
TI  - Cryopreservation of human adult hepatocytes for use in drug metabolism and
      toxicity studies.
AB  - 1. Human hepatocytes were cryopreserved for up to 14 days at -80 degrees C and
      the cryoprotection offered by different media investigated in terms of post-thaw
      cell viability and function. 2. Optimal cryoprotection was offered by a solution
      containing dimethylsulphoxide, propylene glycol, acetamide and polyethylene
      glycol 8000 in Leibowitz L15 medium. 3. The cytochrome P450 content and
      activities of the microsomal P450 dependent mixed function oxidase system were
      well maintained at above 70% of fresh cell values throughout the cryopreservation
      period. However, the activities of the cytosolic enzymes studied, glutathione S
      transferase and glutathione reductase, were not well maintained; they declined to
      < 40% of fresh cell values after storage of cells for 14 days at -80 degrees C.
      The membrane environment may protect microsomal enzymes from denaturation by
      freeze-thaw damage. 4. After cryopreservation, viability of human hepatocytes was
      higher than that of rat hepatocytes preserved under identical conditions. For
      human cells maximum post-cryopreservation viability was 67% after 24 h at -80
      degrees C; this declined to 49% after 14 days storage at -80 degrees C. In
      addition post-cryopreservation human hepatocytes remained > 70% viable when
      incubated at 37 degrees C in suspension compared with only 46% of rat
      hepatocytes. This indicates that human hepatocytes can withstand freeze-thaw
      damage better than those from rat. 5. The results of this study define optimal
      conditions for cryopreserving human hepatocytes. Although microsomal enzyme
      activities are retained post-cryopreservation, the decrease in viability of
      thawed cells upon incubation at 37 degrees C suggests that caution should be
      exercized when using cryopreserved cells to study integrated drug metabolizing
      pathways in man in vitro.

PMID- 8135043
TI  - Conjugation of benzoic acid with glycine in human liver and kidney: a study on
      the interindividual variability.
AB  - 1. The rate of conjugation of benzoic acid with glycine was measured in the
      homogenates of 110 specimens of human liver and in 67 specimens of human renal
      cortex. 2. The assay for the formation of benzoyl glycine consisted of measuring
      the formation of benzoyl glycine from (14C) benzoic acid and glycine in the
      presence of coenzyme A and ATP. 3. In human liver, the mean (+/- SD) and
      coefficient of variation for the formation rate of benzoyl glycine were 254 +/-
      90.5 nmol min-1 per g liver and 36%, respectively. There was a weak, but
      significant, negative correlation (r = -0.339, p < 0.001) between the rate of
      formation of benzoyl glycine and the liver donor's age. 4. In the human kidney,
      the rate of benzoyl glycine formation was normally distributed. The mean (+/- SD)
      and coefficient of variation were 321 +/- 99.3 nmol min-1 per g kidney and 31%,
      respectively. 5. These in vitro results are consistent with the view that the in
      vivo rate of conjugation of carboxylic acid with glycine varies among subjects
      and is normally distributed.

PMID- 8135044
TI  - Metabolism of benzbromarone in man: structures of new oxidative metabolites, 6
      hydroxy- and 1'-oxo-benzbromarone, and the enantioselective formation and
      elimination of 1'-hydroxybenzbromarone.
AB  - 1. The uricosuric drug benzbromarone is extensively metabolized in man and two
      main metabolites are formed: the previously characterized 1'-hydroxybenzbromarone
      (metabolite M1) and an arylhydroxybenzbromarone (metabolite M2) of unknown
      structure. A dimethyl derivative was isolated from urine after methylation and
      was characterized by gas chromatography-mass spectrometry (g.l.c.-m.s.) and high
      resolution nuclear magnetic resonance spectroscopy as 4''-O-methyl-6
      methoxybenzbromarone; the structure of M2 therefore is 6-hydroxybenzbromarone. 2.
      A minor metabolite was similarly characterized as 1'-oxobenzbromarone by
      comparison with authentic synthetic samples and is a product of biodegradation
      and not an artifact derived from the in vitro oxidation of 1'
      hydroxybenzbromarone. Further minor metabolites were detected and were
      provisionally characterized by g.l.c.-m.s. after derivatization and include: 2'
      hydroxybenzbromarone (an isomer of 1'-hydroxybenzbromarone); 1',6
      dihydroxybenzbromarone; dihydroxy-aryl-benzbromarone; and two structure isomers
      of 6-hydroxybenzbromarone. Debrominated metabolites were not detectable. 3.
      Benzbromarone is hydroxylated in vivo at the prochiral centre C1' to 1'
      hydroxybenzbromarone; analysis of 1'-hydroxybenzbromarone from plasma and urine
      extracts by h.p.l.c. using a chiral column revealed that two peaks were eluted
      which showed a mean enantiomeric ratio of 2.1 for plasma and 7.3 for urine; these
      data demonstrate that the formation and elimination of this metabolite is
      enantioselective; the absolute configuration of the 1'-chiral centre is presently
      unknown.

PMID- 8135045
TI  - [The recognition of normal emotions and emotions in affective disorders].
AB  - Recognition of emotions by face expression was studied in 20 healthy subjects and
      20 patients with endogenous depression. Pictures of sad, laughing and neural
      faces were displayed on computer screen and administered to the center of the
      visual field and to the right or left visual hemifields during 40-160 ms. Healthy
      subjects demonstrated more accurate recognition of emotional expression than the
      neutral expression; the right hemisphere dominated in discrimination of laughing
      faces. Depressed patients showed the overall impairment of facial expression
      recognition, which was the most significant for discrimination of sad faces;
      there were no interhemispheric difference. Discriminant analysis showed that
      activity of the right hemisphere is crucial for discrimination of healthy
      subjects and patients with endogenous depression. Possible mechanisms of
      impairment in recognition of emotional facial expressions in depressed patients
      are discussed.

PMID- 8135046
TI  - [The significance of emotional processes in man in the mechanisms of analyzing
      the effect of varying contrast stimulation].
AB  - We estimated the role of emotional processes in regulation of the structural
      afferentation of varying contrast in healthy young subjects by means of VEP
      recording and investigation of Cattell factors (C and Q4). The amplitude of N70
      in all the subjects and that of N150 in subjects with the high stress
      characteristics were in a direct ratio with the contrast of the stimuli. For the
      persons with the low stress characteristics an inverse ratio was observed in the
      occipital-parietal leads while in the frontal areas a switching-over control
      mechanism was manifested.

PMID- 8135047
TI  - [The perception of an odogen is proportional to the activity of the autonomous
      nervous system in man].
AB  - Women aged 18-26 characterized according to R. M. Baevskii's
      cardiointervalometric criteria by the balance between sympathetic and
      parasympathetic activities ("normotonicity") participated in the experiments.
      Sniffing subthreshold concentrations of cordiamin solution vapour during 7-9 s
      was revealed to increase activity of the sympathetic nervous system and heart
      rate frequency with a decrease of its variability. Normotonic subjects with
      predominance of the parasympathetic activity were found to have lower thresholds
      of the odogen detection and to be more cardioreactive to the subthreshold odogen
      than the "normotonics" with slight predominance of the sympathetic activity.

PMID- 8135048
TI  - [Fields of increased activity: the electrophysiological correlates].
AB  - The peculiarities of the spatial-frequency organization of fields of increased
      activity in human cerebral cortex were evaluated by the index of the spatial
      potentials' synchronization. The method of topographic mapping of biopotential
      coherent structures permitted to reveal the principle of formation of the
      increased activity fields: the spatial interaction of coherent structures of
      different frequencies or quantum-frequency superposition of synchronous EEG
      waves. This conclusion is based on a fact of the linear relationship between the
      intensity of a field of increased activity and a number of interacting coherent
      structures in it. The obtained data enlarge the ideas on the mechanisms of the
      origin of local activation processes in the human cerebral cortex and the
      possibility of their use for investigation of the neurophysiological base of the
      mental processes.

PMID- 8135049
TI  - [Adaptive-compensatory restructurings of the intrahemispheric interaction of
      electrical processes in the human brain in brain stem lesions].
AB  - In 50 patients with focal lesions of the brainstem was analysed the postsurgery
      dynamics of the interhemispheric interaction (by the characteristics of EEG
      coherence). Was shown a specific participation of the left and the right
      hemispheres in a realization of postoperative compensatory brain reactions. In
      survived patients in early terms after surgery the phase was revealed in which
      coherence in the left hemisphere exceeded that in the right one and the
      difference being significant for the frontal areas. This phenomenon reflected
      higher reactivity of the dominant hemisphere in a realization of the adaptive
      reactions of the CNS. Right hemispheric EEG coherence in general had lower values
      and was more inert. It dominated under the conditions when only vegetative
      regulation remained before the lethal exit.

PMID- 8135050
TI  - [A dynamic comparison of the interhemispheric asymmetry in the coherence of the
      human EEG in tumorous lesions of the diencephalic and hemispheric brain
      structures under different conditions of cerebral compensation].
AB  - In patients with diencephalic (30 persons) and hemispheric tumors (17 persons
      with the left-side and 18 ones with the right-side localization) EEG coherence
      was studied before and in early terms (12 days) after surgery in comparison with
      the right-handed healthy subjects. It was shown that integral coherence asymmetry
      coefficient before surgery were informative for a prognosis of the postsurgery
      treatment. Changes of absolute coherence levels in the central-frontal cortical
      areas were also informative. In patients with the light postsurgery course of
      treatment coherence levels were higher than those in the healthy subjects and
      increased after surgery. They decreased in patients with aggravated character of
      postsurgery period. Recovery terms were shorter in patients with the left
      hemispheric tumor localization than those with the right hemispheric one. The
      similarity of EEG coherence changes was observed in patients with the
      diencephalic and right hemispheric tumor localization. These results suppose the
      functional connections between these structures which are significant for
      compensatory processes in early terms of postsurgery period after brain tumor
      ablation.

PMID- 8135051
TI  - [The use of computer technology in pediatric neuropsychology].
AB  - The paper is dedicated to creating methods of computerized diagnostics adequate
      to the problems of children neuropsychology. An original battery, based on the
      principle of psychometric approach to diagnostics, was used. Z-scaling was
      utilized in processing the data. 39 children with spastic hemiparesis, aged 9-10
      years, and 40 healthy children, aged 8-9 years, were examined. The results were
      compared to the age norms and were recalculated into Z-scales; thus it became
      feasible to discern reliable deviation of the parameters from the mean level,
      taking into account their variance. Further processing of the data obtained was
      carried out using a special procedure based on Bayes method. This procedure
      permitted not only to evaluate the mean group characteristics of the children
      with focal brain damages but also to obtain individual topic diagnoses. Validity
      of the method was tested. 85% coincidence of the clinical and test results was
      reached. A conclusion is drawn on the reliability of this method for diagnosing
      focal brain damages in children with residual encephalopathies. Using this
      computerized procedure is a promising direction in further advance of children
      neuropsychology methods.

PMID- 8135052
TI  - [The neurochemical mechanisms of the participation of individual neurons in the
      processes of foresight and assessing the results of behavioral activity].
AB  - Chemical sensitivity of neurons of the cat's visual cortex was studied at
      successive stages of food-procuring behaviour, formed as an instrumental act with
      a reinforcement or under the conditions of unexpected appearance of milk.
      Biologically active substances were microionophoretically applied to single
      neurons of the visual cortex. During the period of anticipation and perception of
      milk under these two conditions neurons of the visual cortex had different
      chemical sensitivity to acetylcholine and noradrenaline. The dynamics of spike
      activity in these processes depended on protein synthesis reactions in neurons.

PMID- 8135053
TI  - [The sequelae of the intraspecific isolation of adult rats (right-handed, left
      handed and ambidextrous animals)].
AB  - We studied the influence of social isolation at the age of 2 months on zoosocial
      behaviour of mixed-bred male rats with different paw preference. Paw preference
      was determined in the test of reaching for food in the horizontal tube. The level
      of aggression but not sociability was found to increase significantly in dextral
      and ambidextrous late isolants. In sinistrals the increase of sociability but not
      aggression was observed. Analysis of probabilistic ethological structure of
      aggressive behaviour showed its validity and revealed the appearance of
      pathological aggression as a result of isolation in all groups of animals. Being
      connected with a disfunction of the regulating role of the right brain hemisphere
      this feature of aggressive behaviour is most pronounced in dextrals and
      ambidextrals.

PMID- 8135054
TI  - [The effect of exogenous gangliosides on the formation in rats of instrumental
      movements with tactile control].
AB  - The process of learning and memorization of instrumental reaching movements with
      pressure on an operandum by a preferable forepaw were studied in white rats after
      ganglioside injections. The coursed of learning in control and ganglioside
      injected animals were shown to be alike while some ganglioside treated rats
      demonstrated increased motor activity. After a 5-week interval animals of both
      groups were able to perform quick reaching movements, but the storage of ability
      to push the operandum during the defined time was revealed only in ganglioside
      injected group. It may be considered that the ganglioside injections support the
      long-term storage of learned movements with tactile control.

PMID- 8135055
TI  - [The comparative efficiency of exploratory and conditioned-reflex feeding
      behaviors: the relative improvement in the former and the lag in the latter in
      amygdalectomy in rats].
AB  - Food-taking behaviour of two groups of rats (normal ones, N, and those with
      amygdalar lesions, AL) was compared to each other in two experimental situations:
      running to the feeding-cup in a new situation and the same after the learning
      procedure. In the first case the efficiency of food-taking behaviour was found to
      be higher in AL rats than that in N rats. On the contrary, in the second
      situation, the efficiency of food-taking was lower in AL rats. This difference
      was supposed to be connected with two factors: motivation (in a new situation)
      and mastering the environment (after learning). It was assumed that after AL the
      rats with a deficit of analytical-synthetic process became primarily oriented
      towards inborn programs. A sudden increase of food reinforcement resulted in AL
      rats in a reduce of feeding activity and an increase of general activity
      resembling much the effect of 5-HT in the limbic system.

PMID- 8135056
TI  - [The effect of new ACTH fragments on the behaviors of self-stimulation, avoidance
      and grooming in rabbits].
AB  - We studied the influence of new cyclic analogues of ACTH fragments EHFRWGKPVG-NH2
      and KHFRVG-NH2 on self-stimulation (SS) and active avoidance (AA) behaviour.
      Intraventricular injection of EHFRWGKPVG-NH2 in low doses (0.5-2.5 mcg) was shown
      to increase, that in higher doses (4-5 mcg) to decrease SS frequency. Injection
      of KHFRWG-NH2 in doses of 0.1-5 mcg resulted in 25-30% decrease of SS frequency
      during the first 15 min, its subsequent return to the background level and
      repeated decrease. In 24-48 h SS was 5-8% higher than the background level and
      practically was unchanged in the course of 2 h of experiment. When testing AA
      behaviour EHFRWGKPVG-NH2 in doses of 0.5-2 mcg induced twice shorter "anxiety
      time" and longer latency of AA. Both fragments (0.1-5 mcg) evoked excessive
      grooming. These effects persisted for 24-72 h. The role of the cyclic analogues
      of ACTH fragments in the mechanisms of positive and negative reinforcement is
      discussed.

PMID- 8135057
TI  - [The spectral-correlational analysis of the electrical activity of the rabbit
      brain in the organization of a goal-directed blinking reaction ].
AB  - At organization of the blinking reaction directed to a cessation of the
      motivational hunger dominant the spectral power of biopotentials of the frontal,
      sensorimotor cortical areas and the blinking cortical centres of both eyes, VMH
      and LH increases in the range of the delta- and theta-frequencies. Coherence
      (Coh) of electrical activity of the frontal and sensorimotor cortical areas
      increases, Coh between potentials of the swallowing cortical area and the
      blinking cortical zones corresponding to the trained and non-trained eyes is
      being asymmetrically reconstructed. Coh function of the electrical activity of
      the LH, VMH and potentials of different cortical areas changes uniformly. Coh of
      electrical activity of the VMH and LH, NIII and MPO increases in the whole
      analysed frequency range, Coh between potentials of the MPO and LPO, LPO and VMH
      increases in the delta- and decreases in the theta- and alpha-frequency ranges.
      It is suggested that in the process of preparation of the goal-directed reaction
      all the cerebral cortex areas and subcortical structures under study related to
      alimentary motivation and the blinking function are involved into the dominant
      constellation.

PMID- 8135058
TI  - [The behavioral reactions of fresh-water crayfish to sensory exposures: the
      autonomic components].
AB  - Sudden changes of the environment such as a short-lasting shadowing of an animal,
      placing of some small objects into the tank, light vibrations of the bottom etc.
      Caused vegetative responses in the freely moving native crayfish Astacus astacus
      and the American crayfish Procambarus cubensis adapted for many generations to
      aquarium habitat. We observed mainly a sudden decrease of ECG-frequency
      correlated with similar changes in the electrical activity of the muscles moving
      the specific ventilatory appendages, scaphognathites (scaphognathite-gram, SGG).
      Rise of the ECG and SGG rate was shown during and after the illumination of dark
      adapted animals. The rate changes could be coincided with different changes of
      the amplitude of both ECG- and SGG-waves. It should be noticed that these
      vegetative responses took place mostly without any body movements of the animal.
      We suggest that the crayfish responses to sudden environmental changes are
      similar to mammalian orienting response; probably they also include an emotional
      component.

PMID- 8135059
TI  - [Vision in the snail: the morphology and electrical activity of the optic nerve].
AB  - Light stimulation of a snail's eye elicits spikes in the optic nerve with the
      latency less by 150-170 ms than that of a corresponding retinal ERG-reaction.
      This period is constant independently of the intensity of stimulus. Sensory part
      of the optic nerve consists of at least three types of fibres defining action
      potentials with different amplitudes and thresholds. Sensory branch of the optic
      nerve is terminated in the metacerebrum by two separate sets of axon terminals.

PMID- 8135060
TI  - [The properties of long-term posttetanic heterosynaptic depression in the cat
      motor cortex].
AB  - It is shown that in the neocortex (like in the hippocampus) the long-term
      heterosynaptic depression (LTD) may exist. The effect appears as a long-term
      decrease of the probability of the monosynaptic responses in the afferent input
      to the recorded neuron after the conditioning tetanization of the other afferent
      input to the same neuron. The main properties of the heterosynaptic LTD are its
      longevity, cooperativity and lack of input specificity. The heterosynaptic LTD in
      the unconditioned input and the LTP or the homosynaptic LTD in the conditioned
      input can develop in parallel or independently of each other. It is supposed that
      the heterosynaptic LTD (like the LTP and the homosynaptic LTD) is Ca-dependent
      phenomenon and for its induction a certain level of depolarization of the
      membrane under the inactive (during conditioning) synapses must be achieved. The
      heterosynaptic LTD may provide for the "contrasting", i.e. the relative increase
      of the efficiency of the activated synapses, and probably be effective in such a
      phenomenon as forgetting.

PMID- 8135061
TI  - [The effect of moderate doses of ethanol on the evoked neuronal activity of the
      sensorimotor cortex].
AB  - Influence of acute administration of ethanol in moderate doses (170-1200 mg/kg,
      intraperitoneally) on the evoked activity of sensorimotor cortical neurons in
      response to electrical stimulation of the contralateral forelimb was studied in
      outbred rats never earlier exposed to ethanol action. During the first 20-25 min
      of ethanol action whether augmentation or attenuation in the level of neuronal
      reactivity could occur as well which in both cases could be accompanied by
      significant variability of latencies in poststimulus discharges and
      destabilization of their patterns. Expressed modifications in neuronal patterns
      at the first stage of ethanol action suggest that ethanol destabilizes evoked
      reactions of sensorimotor cortical neurons to afferent stimulation. This
      underlines the need for more complete approach to investigation of primary CNS
      reactions to ethanol paying more attention to temporal succession of origin and
      flow of these effects. Possible relations between oppositely directed primary
      reactions of single cortical neurons and individual characteristics of perception
      of different animals are discussed.

PMID- 8135062
TI  - [The spatial synchronization of the potentials in the background and evoked ECoG
      of a neuronally isolated strip of rabbit cortex].
AB  - Conditions of formation of potentials' spatial synchronization in the neuronally
      isolated cortical slab were studied in anaesthetized rabbits in acute
      experiments. Cortical potentials in all recording points of the slab were similar
      to each other. Seizure potentials induced by electrical stimulation spread over
      the slab and became synchronous in all points of recording. The neuronal division
      of the slab in two parts did not lead to a disturbance of initial synchronization
      of the background potentials in the isolated parts of the slab, while seizure
      potentials after electrical stimulation spread only over one part of the slab.
      These results suggest that the spatial synchronization of the EEG activity is a
      result of activity physically spreading from subcortical structures.

PMID- 8135064
TI  - [The dynamic behavioral changes and the compensatory-restorative processes in
      rats following the destruction of the red nucleus and the ventrolateral thalamic
      nucleus].
AB  - In white non-strain rats with elaborated instrumental responses preliminary
      section of the rubro-spinal tract was shown to promote the compensatory
      restorative processes after the destruction of the red nucleus and the
      ventrolateral thalamic nucleus. Facilitation observed is considered to be a
      result of transfer of the motor activity to the cortico-spinal system due to
      activation of the inferior olive and the cerebellum.

PMID- 8135063
TI  - [The amiridin and tacrine modulation of the cholinoreceptor activity and
      plasticity of snail neurons: the phenomenology and mechanisms].
AB  - The effects of amiridine and tacrine on the membrane potential, activity and
      plasticity of cholinoreceptors have been studied using the recording of
      intracellular and transmembrane currents in identified neurons of Helix lucorum.
      Amiridine and tacrine (1-100 mcM) have no noticeable effects on the membrane
      potential of the cells. Both compounds modulate the activity of cholinoreceptors
      to judge from their influence on the inward current induced by the local
      acetylcholine (ACh) application: they increase the duration of the current with a
      two-phase effect on the amplitude (a short-latent intensification with a
      following decrease). Amiridine and tacrine intensify ACh current extinction
      induced by repeated ACh application to the soma. Acetylcholinesterase inhibitor
      physostigmine has a similar modulating effect on ACh current and its extinction.
      It impedes the modulating effects of amiridine and tacrine. Amiridine and
      physostigmine directly affect cholinoreceptors and ion channels controlled by
      them changing in a similar way the current-voltage curves of ACh-current and
      approximating it to the equilibrium potential of chloride ions. Modulating
      effects of amiridine, tacrine and physostigmine on the activity and plasticity of
      cholinoreceptors may be supposed to be caused by their direct membrane
      cytoplasmic action.

PMID- 8135065
TI  - [The limitation of the intensity of the stress reaction under open-field test
      conditions through the adaptation of rats to cold and physical loading].
AB  - Male Wistar rats' adaptation to the periodical cold exposure (3 hours daily, 6
      times a week within 2 months at the air temperature of 1-2 degrees C) and to the
      exercise training (swimming 1 hour daily, 6 times a week within 2 months at the
      water temperature of 32-33 degrees C) was resulted in a limitation of motional
      and vegetative manifestations of the stress reaction in the "open field" test.
      Activation of the stress limiting systems in the organism could be one of the
      main causes of these adaptive effects. There was an elevation of beta-endorphin
      concentration and that of the ratio "prostacycline/thromboxane" in some tissues
      of adapted animals.

PMID- 8135066
TI  - [The functional and morphochemical characteristics of the hippocampal neurons
      during the formation of trace processes in old rabbits].
AB  - Trace rhythmic activity of dorsal hippocampal neurons were studied after the long
      lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the
      forelimb in alert young (5-7 months), middle-aged (54-65 months), and very old
      (66-84 months) rabbits. During aging the number of spontaneously active neurons
      was shown to be significantly decreased, the proportion of slowly firing neurons
      to be increased, the interspike intervals and intervals between spike groups to
      lengthen, and the number of spikes per a group to be reduced. Spectral analysis
      of neuronal firing rate revealed that ability to reproduce the rhythm of the
      previous stimulation declined with age. No appropriate rhythms were found in
      hippocampal neurons of the old animals. Morphological and cytochemical analysis
      of the hippocampal neurons revealed changes in nuclear-cytoplasmic relations and
      also a fall of protein synthesis in the neurons of the old animals. The observed
      deteriorations may explain the impairment of trace rhythmic activity in
      hippocampal cells with age.

PMID- 8135068
TI  - [The Asratian Prize 1993].

PMID- 8135067
TI  - [The intraventricular administration of quinolinic acid improves the formation of
      an active avoidance conditioned reflex in rats].

PMID- 8135069
TI  - Swine erythrocyte fractionation in Percoll density gradients.
AB  - A method for the fractionation of swine erythrocytes according to age using
      Percoll is described. Centrifugation of erythrocytes on discontinuous Percoll
      gradients yielded four fractions of erythrocytes. To ascertain that each fraction
      of erythrocytes represented a different age group, the activities of hexokinase
      (Hx), aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPD), pyruvate kinase
      (PK), lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD) and 6
      phosphogluconate dehydrogenase (6PGD) were determined. These enzyme activities
      decreased successively from the top to the bottom fractions of the centrifuged
      column. Young erythrocytes obtained from the upper fractions of the centrifuged
      column exhibited a higher activity of each enzyme than that found in the heavier
      and older erythrocytes at the bottom fraction. This method is proposed as the
      most appropriate for use as an aid in distinguishing the presence of a young
      erythrocyte population.

PMID- 8135070
TI  - An outbreak of abscess disease in goats in Saudi Arabia.
AB  - Sixty-one out of 165 goats showed abscesses in various body lymph nodes, mainly
      in the head, neck and shoulder region. The specimens cultured revealed the growth
      of Staphylococcus aureus subspecies anaerobius. Accordingly an abscess disease
      "Morel's disease" was diagnosed in affected goats.

PMID- 8135071
TI  - Effects of oral administration of toxic levels of lead and selenium upon
      concentration of different elements in the liver of broiler chicks.
AB  - Broiler chicks fed lead or selenium for varying periods were later intoxicated
      with two levels of either of these elements. In this way different groups of
      chicks were exposed to lead or selenium alone or a combination of these two. Lead
      caused increased liver concentrations of lead and iron. Selenium administration
      increased liver selenium and iron levels while liver copper decreased. Concurrent
      administration of lead and selenium greatly enhanced the accumulation of both
      elements in the liver and increased the liver iron. Lead partially counteracted
      the depression of liver copper caused by selenium. Mortality due to concurrent
      exposure to lead and selenium was lower when vitamin E was added to the feed.
      Body weights were markedly suppressed by selenium. The concurrent administration
      of lead partially alleviated the growth depression caused by selenium. Selenium
      fed birds had increased relative weights of liver and heart but this increase was
      of lesser degree in birds given both elements.

PMID- 8135072
TI  - Identification of canine glial cells by nonradioactive in situ hybridization.
AB  - Studies on the development of the canine central nervous system and on
      demyelinating diseases demand unequivocal identification of the glial cells. For
      that reason, nonradioactive in situ hybridization (ISH) was performed in primary
      dog brain cell cultures (DBCC) and in brain sections of neonatal dogs. Specific
      RNA probes were used to detect messenger RNA (mRNA) coding for proteolipid
      protein (PLP), myelin basic protein (MBP) and glial fibrillary acidic protein
      (GFAP). PLP and MBP are markers for oligodendrocytes, GFAP for astrocytes.
      Oligodendrocytes positive for PLP and MBP mRNA were found in both DBCC and brain
      sections of neonatal dogs. Astrocytes expressing GFAP specific mRNA were detected
      in DBCC and in brain sections. These cells were evenly distributed in the white
      matter with additional accumulation in the membrana limitans gliae superficialis,
      around the ventricles and blood vessels. ISH clearly improves the study of
      oligodendrocytes in brain sections as, in contrast to the immunohistochemical
      methods, this technique allows to identify individual cells.

PMID- 8135073
TI  - Phycomycosis of the abomasum in Camelus dromedarius.
AB  - Two cases of phycomycosis of the abomasum in dromedary camels are described. In
      one of the cases there is evidence of spread to the liver. The pathology and
      pathogenesis of the disease are discussed. We believe this is the first report of
      phycomycosis in Camelidae.

PMID- 8135074
TI  - Metabolic effect of orotic acid in calves.
AB  - Eight calves (males, Black and White crossbred with Holstein-Fresian) were fed
      milk and milk replacer without (control group) or with potassium orotate (3
      mmol./l.) supplementation for 6 weeks after birth. Orotate depressed the
      biosynthesis of polyamines in mucosa of the gastrointestinal tract (rumen,
      omasum, abomasum, colon) by decreasing of ornithine decarboxylase activity with a
      simultaneous compensatory increase of S-adenosyl-methionine decarboxylase
      activity. A lower concentration of spermidine and spermine in the mucosa of the
      colon was also noted. The above changes were accompanied by increased urinary
      excretion of ornithine and arginine. Calf adaptation to a high OA intake was
      associated with an increased activity of the OA metabolizing enzyme complex
      (orotate phosphoribosyl transferase and orotidine monophosphate decarboxylase) in
      the liver, while urinary OA losses diminished with age. Increased concentrations
      of uracil and uridine in the liver and higher urinary excretion of pseudouridine
      in OA-fed calves was also observed. Stimulation of pyrimidine metabolism by OA
      depressed purine synthesis, which was reflected by a decrease of urate,
      hypoxanthine, and xanthine concentration in the liver. Interestingly OA enhanced
      urate excretion by the kidneys. OA strongly affected lipid metabolism in calves
      because total cholesterol, LDL-, and HDL-cholesterol, and triglycerides in blood
      plasma decreased while triglycerides accumulated in the liver of OA-fed calves.
      Milk OA in concentrations characteristic of cows with hereditary orotic aciduria
      exerts an unfavourable effect on the metabolism of polyamines, purines, and
      lipids in calf tissues.

PMID- 8135075
TI  - Diagnosis of bovine cardiomyopathy by electrolyte and protein analysis.
AB  - The intention of this paper was to describe a reliable method for the diagnosis
      of cardiomyopathy (CMP) in adult cattle and, in particular, a clear distinction
      between CMP and inflammatory heart disease (IHD). In a first study we performed a
      linear discriminant analysis using serum and urine electrolyte concentrations
      (sodium, potassium, calcium, magnesium, chloride, phosphate, iron, creatinine) of
      33 CMP-affected and 35 healthy cattle. This analysis allowed to classify all the
      animals of both animal groups correctly. In a second study, we examined the
      clotting reaction of the glutaraldehyde coagulation test (GCT) in cardiomyopathy
      (n = 49), inflammatory heart diseases (n = 9) and in healthy cows (n = 35). 96%
      of the CMP-sick and all the control animals showed a clotting time above 10
      minutes. In the IHD group, the clotting time was always below 10 minutes. In a
      third study, we applied the combination of discriminant analysis and GCT to a new
      set of CMP- (n = 14) and IHD-affected (n = 9) as well as to healthy cattle (n =
      15). The classification was correct in 93% of the CMP-sick and in all the IHD
      affected and the control animals. The results are discussed.

PMID- 8135076
TI  - Immunohistological and immuno-electron microscopic localization of fibronectin in
      chicken bone marrow.
AB  - Fibronectin (FN) was immunolocated in chicken bone marrow with the PAP-technique
      by light and electron microscopy. A pre-embedding method was employed for
      immunolabelling the specimen for electron microscopy. Blood vessels and lining
      cells of capillaries and sinusoids were labelled for FN. Monocytes,
      intrasinusoidal macrophages, and stromal elements in the extrasinusoidal
      compartment. The distribution of FN in the chicken bone marrow supports the
      assumption that FN facilitates extravascular haematopoiesis, especially migratory
      processes, whereas its contribution to intravascular haematopoiesis seems less
      likely and needs further investigation.

PMID- 8135077
TI  - Field research on veterinary problems in group-housed sows--a survey of lameness.
AB  - Investigations on two experimental farms with group-housing revealed that
      lameness occurred mainly at the hind legs of sows, with a higher incidence in
      first parity sows. The highest incidence of lameness was seen during the first 2
      months of gestation and the highest prevalence in the last 2 months of gestation.
      No relation could be established between lameness of a sow in the last month of
      gestation and reproduction results. The incidence of claw lesions increased too,
      during the group-housing during pregnancy and was higher compared to sows kept in
      crates. This increase was clearest in first parity sows. In addition the
      observations suggest a pattern in the course of development of lesions. Claw
      lesions mainly occur on the outer claws of a sow. For two types of lesions left
      right symmetry has been established for both the hind and the front legs. On the
      level of the individual animal there was no relation between the incidence of
      claw lesions and lameness.

PMID- 8135078
TI  - The correlation between the dose and distribution of intratendinous fluid
      injections in the flexor tendons/ligaments of the horse.
AB  - An in vitro study was carried out to define the correlation between the dose and
      distribution of intratendinous fluid injections in the different flexor
      tendons/ligaments of the palmar/plantar, metacarpal/metatarsal region of the
      horse. Injection of 0.1-0.2 ml resulted in a local intratendinous fluid depot
      showing minimal abaxial spreading and more extensive proximodistal expansion. If
      0.3-0.5 ml was injected the abaxial spreading remained minimal but the
      proximodistal expansion increased significantly, the depots in the axial
      proximal, mid and distal region flowing together. Also minimal peritendinous
      fluid accumulation was visible. Increasing the dose from 0.5 to 2 ml resulted in
      extensive abaxial spreading and peritendinous accumulation. These findings
      indicate that the 2 ml injection recommended in the veterinary literature
      probably represents an oversized dose. If a small lesion is present a 0.1-0.2 ml
      intratendinous injection should be adequate. The injection should preferably be
      guided by ultrasonography to allow precise deposition of the drug into the
      lesion. In larger local defects a depot of 0.3-0.5 ml apparently is sufficient.
      If a very large portion of the tendon is injured, several depots of 0.3-0.5 ml
      approximately 5 cm apart is preferred to cover the full proximodistal extension
      of the lesion.

PMID- 8135079
TI  - The effect of aging on laboratory values in dogs.
AB  - The main objective of this study was to examine age-associated changes in
      laboratory values in dogs in order to establish standard values for dogs of a
      certain age. These standard values could serve to judge the health status of
      individual dogs and possibly estimate their remaining life expectancy. Thus,
      haematological and immunological parameters, plasma constituents, kidney
      characteristics and the capacity of homeostasis were determined in German
      shephard dogs (0.5-13.5 years) and beagles (4-9 years). Significant changes were
      noted. We detected that the number of white blood cells declines with age. The
      change in a number of organ specific enzymes indicates organ involution and
      increased cell death. Increased plasma glucose levels and a decreased glucose
      tolerance point to a diminished sensitivity of tissue to concentrations change
      due to a decrease in organ production and changes in the immune system, which are
      also reflected in an impaired lymphocyte proliferation capacity. These factors
      lead to an increased blood sedimentation rate. Cortisol increases might reflect a
      reduced stress resistance. Age-related decreases in aldosterone concentration and
      PAH-clearance were also found.

PMID- 8135081
TI  - Statistical evidence that endogenous reverse triiodothyronine (rT3) may affect
      oxygen consumption in food deprived chickens.
AB  - Exogenous rT3 decreases O2 consumption in mammals and birds. Until now a
      correlation coefficient and a regression equation have not been presented.
      Statistical evaluation seems to be requisite for verifying the answer to the
      question of whether endogenous rT3 may be able to reduce O2 consumption in birds
      where the normal level of plasma rT3 is 10 times less than the corresponding
      level of T3. Food deprived chickens (for 48 h) were used in this study because
      fasting enhances plasma rT3. The results revealed a reciprocal relation of T3 and
      rT3 in the circulation. Reverse T3 began to increase when T3 decreased to a
      plateau at 53.9% of initial level. As expected a reciprocal relationship was
      obtained (r = -0.749; n = 36) between plasma rT3 and O2 consumption. The
      regression line was calculated according to the equation: Y = -0.388X + 0.856.
      This relation differs from the linear relationship between T3 and O2 consumption
      (r = 0.796; Y = 0.107X + 0.449). The regression line lies in the range of 0.122
      0.778 nmol rT3/l, which is found in some physiological conditions in birds where
      elevated plasma rT3 occurs. This suggests that endogenous rT3 may participate in
      modifying O2 consumption in birds. Using the rT3:T3 ratio the correlation
      coefficient was somewhat higher (r = -0.831; Y = -0.673X + 0.831) suggesting
      common involvement of both triiodothyronines in the reduction of O2 consumption
      during food deprivation. The drop in O2 consumption after 48 h of food
      deprivation was 28.4%; decreased T3 and increased rT3 may participate in 15.4%
      and 13.0% of this fall, respectively. The hypometabolic effectiveness of rT3
      seems to be greater than the hypermetabolic effectiveness of T3, since a smaller
      increase of plasma rT3 was needed to reduce O2 consumption compared to the amount
      of T3 necessary to enhance it.

PMID- 8135080
TI  - [Experimental studies of the pathogenesis of rumen acidosis in sheep].
AB  - Rumen acidosis was provoked in 13 cross-bred sheep by feeding oat (32 g/kg body
      weight) or wheat of different grinding levels (26 g/kg). Development of the diet
      related disease was studied in 8 fistulated sheep fitted with a permanent rumen
      cannula and with implanted jugular vein catheter by analysing blood and rumen
      fluid sampled up to 48 hours after feed intake. Ingesta of the different segments
      of the digestive tract were collected from 5 sheep, necropsied 8 and 12 hours
      after feeding respectively. Concentrations of glucose, L- and D-lactate were
      measured in blood and digesta by enzymatic methods. Concentrations of
      amylopolyglucans and pH values were analysed in the digesta. Whereas the plasma
      concentration of glucose and L-lactate rose with a maximum at 8 to 12 hours after
      feeding, that of D-lactate was maximally increased after 24 hours. High
      concentrations of amylopolyglucans, glucose, L- and D-Lactate were found in the
      whole digestive tract 8 and 12 hours after feed intake. It is concluded from the
      results obtained that sheep show characteristics of monogastric intestinal
      digestion with the release of considerable amounts of glucose and of both lactate
      isomers after feeding fine distributed starch.

PMID- 8135082
TI  - Effect of verapamil and sodium nitroprusside on the potassium contracture of
      smooth muscle strips from the reticular groove of adult cattle.
AB  - The effects of verapamil and sodium nitroprusside on smooth muscle strips from
      the floor of the reticular groove of adult cattle were studied. The mechanical
      activity of the muscle strips was recorded isometrically. Depolarization was
      induced with cumulative KCl concentrations (8.8-42.4 mmol/l) in Tyrode solution.
      This response was extracellular Ca2+ dependent. Verapamil and sodium
      nitroprusside caused a concentration dependent reduction of the KCl-induced
      contraction of the reticular groove muscle preparations; their IC50 were 3.9 x
      10(-6) mol/l and 1.4 x 10(-4) mol/l, respectively. Pre-incubation with both
      antagonists (30 min) before KCl addition showed that sodium nitroprusside (10(-6)
      mol/l) did not affect, but verapamil (10(-6) mol/l) inhibited the KCl response of
      the muscle preparations. CaCl2 caused a concentration dependent (0.25-7 mmol/l)
      contraction of the KCl-depolarized muscle strips. Pre-incubation with verapamil
      (10(-6) mol/l) and sodium nitroprusside (10(-6) mol/l) before CaCl2 addition
      inhibited the response for about 80% and 20% respectively. These results indicate
      that action of verapamil may be related to voltage-dependent channel blockade.
      However, the nitroprusside action could not be completely attributed to these
      channels.

PMID- 8135083
TI  - [Pulsed Doppler echocardiography measurement in healthy warmblood horses].
AB  - Twenty adult warm blooded horses (body weight 585 +/- 59 kg) were evaluated with
      pulsed doppler echocardiography. Locations for the transducer and the sample
      volume were determined to get typical blood flow tracings of the equine heart.
      Angle of doppler beam was between 37 degrees and 40 degrees in right heart
      atrioventricular flow tract and between 44 degrees and 47 degrees in left heart
      atrioventricular flow tract. Peak blood flow velocity (angle corrected) was 0.71
      +/- 0.17 m/s in tricuspid valve and 0.92 +/- 0.22 in mitral valve. In right and
      left atrioventricular flow tracts in all sample volume positions typical double
      peaked spectral tracings of blood flow were seen. In supravalvular, valvular and
      subvalvular sample volume locations of the ventriculoatrial flow tracts angles
      were between 28 degrees and 33 degrees in right heart and between 34 degrees and
      37 degrees in left heart. Peak flow velocity (angle corrected) was 0.98 +/- 0.13
      m/s in pulmonary valve and 0.92 +/- 0.09 m/s in aortic valve. Paradoxical
      systolic and diastolic flows were seen. The flow velocity tracings were similar
      to those found in man. Flow velocity values of clinically normal horses have a
      wide range like in healthy human beings. Nevertheless flow tracings of healthy
      horses have a characteristical profile and may be helpful in detecting abnormal
      blood flow in heart diseased horses.

PMID- 8135084
TI  - A new quick-test for semiquantitative determination of beta-hydroxybutyric acid
      in bovine milk.
AB  - A new test strip for semiquantitative determination of beta-hydroxybutyric acid
      (BHB) in bovine milk has been tested in experimental investigations in three
      lactating cows. After intraruminal administration of butyric acid, the following
      parameters were determined during 7 hours: milk concentrations of BHB
      (quantitatively and semiquantitatively) and acetone (quantitatively), BHB
      concentration in blood and urine (quantitatively), acetone + acetic acid
      concentration in urine (semiquantitatively). The new quick-test proved to be
      highly sensitive and even subclinical or physiological levels of BHB in milk
      could be determined. It seems to be suitable not only for the diagnosis of
      clinically manifest ketosis in dairy cows, but also for the control of the energy
      metabolism on a herd basis and as an indicator of ketogenic feedstuffs in the
      ration.

PMID- 8135085
TI  - Metabolic profiles of white and red-intermediate spinal motoneurons in the
      zebrafish.
AB  - To study the interactions between the citrate cycle and amino acid metabolism in
      zebrafish spinal motoneurons, we composed enzyme histochemical profiles from the
      activities of NAD-linked isocitrate dehydrogenase (NAD-ICDH), glutamate
      dehydrogenase (GDH), succinate dehydrogenase (SDH) and glucose 6-phosphate
      dehydrogenase (G6PDH). The enzyme assays were performed on serially-sectioned
      motoneuron somata. The motoneurons were identified by retrograde tracing from the
      trunk muscle and classified, on the basis of their location in the motor column,
      as those innervating the white, fast glycolytic fibers (WMNs) or those
      innervating the red and intermediate slow oxidative fibers (RIMNs). We found the
      following relationships between enzyme activities in WMNs: GDH correlates with
      G6PDH activity (r = 0.31; p = 0.02) and NAD-ICDH correlates with GDH activity (r
      = 0.37; p < 0.01); correlations between NAD-ICDH and SDH and between SDH and GDH
      are not significant. In RIMNs we found correlations between NAD-ICDH and SDH (r =
      0.34; p = 0.03), between NAD-ICDH and GDH (r = 0.41; p < 0.01) and between GDH
      and SDH (r = 0.50; p < 0.01); the correlation between GDH and G6PDH is not
      significant. The differences in metabolic profiles between WMNs and RIMNs can be
      explained in the following way: in WMNs, alpha-ketoglutarate is drawn off from
      the citrate cycle and is used in amino acid metabolism whereas in RIMNs the
      removal of alpha-ketoglutarate from the cycle is balanced by formation of alpha
      ketoglutarate. The data suggest that the functional role of the citrate cycle
      differs in the two motoneuron populations: in RIMNs energy generation
      predominates but in WMNs a role in biosyntheses seems most important.

PMID- 8135086
TI  - Age-dependent changes of the immunohistochemical distribution of various collagen
      types and structural glycoproteins in the human uterine tube.
AB  - This immunohistochemical investigation deals with the age-dependent localization
      and distribution of types I, III, IV, V, and VI collagen and the structural
      glycoproteins undulin, fibronectin, laminin, tenascin, and vitronectin in the
      connective tissue of the human uterine tube. The stroma of this oviductal region
      consisted of all collagen types. Collagen types I and VI were distributed
      throughout the connective tissue of the mucosa reaching the basal membrane. The
      findings suggest that the amount of these collagen types and type III collagen
      increases in relation to age, since the coarser fibres of the mucosal stroma in
      the uterine tubes of older women were strongly labelled by immunohistochemistry.
      The pattern of undulin reactivity was similar to that of types I and VI collagen.
      The exact quantitative proportions of age-related oviductal changes for types I,
      III, and VI as well as of undulin are still unknown. Type V collagen was
      associated with a fine fibre meshwork in the mucosal stroma. The fibres reached
      the subepithelial zone which appeared membrane-like. The location of type V
      collagen-associated fibres and aldehyde fuchsin-positive fibres characterized in
      our previous studies appears to be identical. Moreover, the structural
      glycoproteins undulin, fibronectin, laminin, tenascin, and vitronectin were
      detected in the mucosal stroma. The staining of fibronectin was less pronounced
      than that of undulin. Laminin was located in the zone of the basal membrane,
      whereas tenascin was mainly found in the mucosal vessels. Contrary to these
      findings, tenascin showed a unique distribution in the region near the basis of
      the mucosal folds in the isthmic part. Vitronectin could be observed in the same
      region of the isthmic part of uterine tubes obtained from younger women. However,
      the zonal localization of vitronectin reactivity was absent in the isthmic part
      of older women.

PMID- 8135087
TI  - Comparison of three histochemical methods for assaying lactate dehydrogenase in
      liver.

PMID- 8135088
TI  - Estramustine induces disorganization of microtubules, perinuclear retraction of
      vimentin and endoplasmatic reticulum, and inhibits cell migration.
AB  - The effects of the mitotic inhibitor estramustine on the cytoskeleton of DU 145
      and AG 1518 cells were studied. Estramustine caused a partial disassembly of
      microtubules and withdrawal of microtubules from the cell periphery, disorganized
      microtubules and delayed regrowth of disassembled microtubules. It also induced a
      spheroid cellular morphology and affected cellular adhesion and survival.
      Sometimes microtubules seemed to be organized from several microtubule-organizing
      centers. The cytoskeleton-dependent cell migration was inhibited in the presence
      of estramustine and the microtubule-interacting vimentin and endoplasmatic
      reticulum retracted to the perinuclear area. Our results show that not only a
      complete disassembly of microtubules, but also disturbances of the microtubule
      network can have dramatic effects on microtubule-dependent processes and
      localization of cellular organelles. These effects could be of importance in the
      treatment of prostatic carcinoma with estramustine.

PMID- 8135089
TI  - Fluorescence microscopic studies and flow cytometric measurements of lectin and
      hormone binding to isolated rat pancreatic acinar cells.
AB  - The binding of fluorescence-labelled lectins and a fluorescence-marked hormone to
      the cell surface of isolated rat pancreatic acinar cells was studied by light
      microscopy and flow cytometric measurements. The pancreatic acinar cells were
      prepared by collagenase digestion. The fluorescence of cells was studied after
      binding of FITC-labelled WGA or UEA I as well as of FITC-marked
      pancreocymin/cholecystokinin (CCK-FITC) in a fluorescence microscope or FACScan.
      The strong binding of lectins was inhibited by preabsorption with the specific
      sugars. In comparison to the lectins the binding of CCK-FITC was low. There were
      two populations of acinar cells with different CCK-FITC binding capacity as
      detected by flow cytometry. The CCK-FITC cell surface fluorescence was
      significantly decreased by preincubation with unmarked hormone as well as with
      the non-labelled lectins. The inhibition of CCK-FITC binding by lectins is
      discussed in respect to a possible competition of the lectins and CCK for the CCK
      receptor.

PMID- 8135090
TI  - Calretinin immunoreactivity in the magnocellular neurosecretory nuclei of the rat
      hypothalamus.
AB  - The distribution of calretinin-immunoreactivity in the magnocellular
      neurosecretory nuclei of the rat hypothalamus was studied using a polyclonal
      antibody and the avidin-biotin immunoperoxidase technique. Calretinin
      immunoreactive neurons were observed in the supraoptic and paraventricular
      nuclei. Additionally, we detected for the first time, immunoreactive neurons
      located in the circularis and fornicals nuclei, and isolated positive neurons
      situated in the hypothalamic area located between the supraoptic and
      paracentricular nuclei. When these results were compared to those obtained in
      previous studies for another two calcium-binding proteins: calbindin D-28k and
      parvalbumin, two major differences may be concluded: a) a different distribution
      of calretinin, especially in the paraventricular nucleus, and b) an expression of
      calretinin lower than calbindin D-28k and higher than parvalbumin in the
      magnocellular hypothalamic nuclei. Of special interest is the fact that
      calretinin is one of the few markers which demonstrates predominantly
      parvicellular neurons in the paraventricular nucleus. Although the exact
      biochemical function of these three calcium-binding proteins remains unknown,
      their uneven and characteristic distributions strongly suggest that specific
      neuronal populations in the hypothalamus may use alternatively different calcium
      sequestering molecules.

PMID- 8135092
TI  - LR Gold and LR White embedding of lung tissue for immunoelectron microscopy.
AB  - The immunogold technique in conjunction with LR Gold or LR White embedding was
      used to localize different antigens in normal rat and mini pig lung tissues.
      Lycopersicon esculentum and Maclura pomifera lectins and diverse cytoskeletal
      antigens such as cytokeratins, beta-tubulin, smooth muscle-actin, tropomyosin and
      villin were labelled well. Factor VIII-related antigen was found in Weibel-Palade
      bodies of endothelial cells. A 10 kDa Clara cell protein was localized in Clara
      cells. The morphological preservation of LR Gold-embedded tissue was superior to
      that of LR White-embedded tissues, but significant differences in antigenicity
      were not seen.

PMID- 8135091
TI  - Light microscopic visualization of monoamine oxidase using a cerium method.
AB  - H2O2-generating monoamine oxidase can be visualized in the light microscope with
      tetrazolium, metal salt (ferricyanide) and coupled peroxidatic oxidation methods.
      Due to methodological draw-backs these procedures do no allow satisfactory
      results. In search for an alternative method a light microscopic cerium procedure
      was designed in which the primary reaction product, cerium perhydroxide, serves
      for the generation of amplified and intensified diaminobenzidine brown. With this
      cerium-diaminobenzidine-H2O2-Co method monoamine oxidase was visualized more
      easily and reliably and with higher sensitivity and more precise localization
      than with the other techniques. At present this method is considered to be the
      procedure of choice and was used to re-investigate and investigate the
      distribution of monoamine oxidase in rats, mice, gerbils, guinea-pigs, marmosets,
      monkeys and man. In these species many cells and tissues showed monoamine oxidase
      activity where the enzyme has not yet been found before and the structures with
      already known monoamine oxidase activity showed an improved localization.

PMID- 8135093
TI  - [Anesthesiological methods in acoustic neuroma surgery using the
      translabyrinthine approach].
AB  - Removal of acoustic neuromas may often imply anesthesiological as well as
      surgical problems, especially in the case of large tumors (> 3 cm) which may have
      come into contact with vital neighbouring structures (brain stem, cerebellum). In
      this paper the use of two different anesthesiological methods during the
      translabyrinthine approach is analyzed and discussed in the light of the
      different needs in this type of surgery. More specifically, anesthesia
      maintenance was assured by constant infusion of either Propofol (4 mg/kg/h) or
      Isoflurane (1-1.5%). Withdrawal of curarization was also planned in order to
      allow the surgeon to take advantage of routine intraoperative facial nerve
      monitoring. Arterial pressure, CO2 and O2 were assessed at prefixed phases of the
      operation. Both anesthesiologic methods proved to be satisfactory during the
      entire surgical procedure. During dissection of the tumoral capsule, an increased
      heart rate (7% of the initial value) was noticed, whilst in only three patients
      (with tumors larger than 3.5 cm) a severe bradycardia, which did not respond to
      Atropine administration and which subsided spontaneously during temporary
      suspension of surgical manoeuvres, occurred. After this preliminary experience,
      the Authors believe that both techniques could have a major role in
      translabyrinthine acoustic tumor surgery and auspicate their further application.

PMID- 8135094
TI  - [Magnetic resonance with GD-DTPA in acoustic neuroma: personal experience].
AB  - Magnetic Resonance (MR) is currently becoming an important diagnostic pool in
      therapy planning and care of patients with tumors of the head and neck. In this
      work MR with GD-DTPA was used to all subjects suffered from acoustic neuroma: in
      18 patients (86%) the diagnosis was possible with sequences obtained without
      contrast medium; in 3 patients (14%) the used of Gd-DTPA was essential in
      diagnosing the tumor. The Authors conclude that MR with Gd-DTPA is helpful in
      revealing neuromas of the internal auditory canal, multiple lesions of
      neurofibromatosis and tumor recurrence.

PMID- 8135095
TI  - [The sub-occipital approach in functional surgery of acoustic neuroma].
AB  - In this study the Authors analyze 380 acoustic neuroma removals carried out from
      1972 to 1992 focusing their attention on 90 attempts to save hearing by employing
      a suboccipital approach. In this series the facial nerve was preserved in 99% of
      the cases with completely normal function in 78%. The cochlear nerve was
      anatomically preserved in 96% of the subjects. According to the Shelton-Brackmann
      classification applied to evaluate hearing results, good hearing (Class A = PTA <
      or = 30 dB; SDS > or = 70%) was obtained in 12% of the cases, serviceable hearing
      (Class B = PTA < or = 50 dB; SDS > or = 50%) in 13%, measurable hearing (Class C
      = any measurable hearing) in 19% and anacusis (Class D) in 56% of the patients.
      CSF leak occurred in 6.6% of the cases, meningitis in 2.2%, paresis or paralysis
      of the ninth and tenth cranial nerves in 3% and ataxia in 2%. In acoustic neuroma
      surgery, hearing preservation is a new but complicated topic. In fact, some
      operative steps--such as the separation of tumor from nerves and arteries, tumor
      mass reduction, exposure of the end of the IAC--certainly influence surgical
      results, but are a matter of uncontrollable variance even within series from the
      same surgeon and render hearing preservation an innovative idea still awaiting,
      however, a controllable procedure. The ethical feasibility of hearing
      preservation is confirmed by our results in which hearing preservation attempts
      using a suboccipital approach have the same morbidity that the translabyrinthine
      route would have in the same patient.

PMID- 8135096
TI  - [The recurrent multifocal pleomorphic adenoma].
AB  - Pleomorphic adenoma (P.A.), the most common tumor of the salivary gland,
      demonstrates a peculiar clinicopathological behaviour for numerous reasons: the
      high recurrence rate following primary surgery (up to 50%), the appearance of
      malignancy (2-9%), the reported number of distant metastases histologically
      identical to the primary P.A. From among 71 cases of benign parotid tumors
      treated from Nov. 89 to Nov. 92 in the ENT Department of "Regina Elena", the
      National Cancer Institute in Rome, six particular cases showed multiple force of
      P.A. recurring after primary surgery performed from 3 to 32 years previously and
      are object of discussion in this study. All of these six cases had multiple
      recurrences, usually manifest as nodular clusters in the parotid area, while in
      three cases appeared as well a recurrence in the soft tissue of the neck, far
      removed from the parotid space, with no involvement of neck nodes as was revealed
      through histological examination following neck dissection. A hypothetical
      mechanism of diffusion is discussed. The Authors agree with the opinion which
      holds the surgeon's inability to successfully eradicate primary tumors
      responsible for the high frequency of recurrences. The surgical technique of
      "enucleation" is, in fact, inadequate in P.A. excision owing the high risk of
      mishandling or rupturing the tumor capsule with a consequent seeding of the tumor
      onto the surgical bed. Lateral lobectomy, with identification of the facial
      nerve, or total conservative parotidectomy (for deep lobe adenoma) are correct
      techniques in treating primary P.A.. The Authors also discuss management of
      recurrent P.A. in relation to facial nerve involvement. Preservation of the
      seventh nerve with eventual post-operative radiation should be considered an
      alternative to nerve sacrifice in selected cases of recurrent pleomorphic
      adenoma.

PMID- 8135097
TI  - [Environmental and occupational risk factors in keratosis of the larynx].
AB  - Laryngeal keratosis may frequently precede the appearance of carcinoma of the
      larynx which might well indicate that these diseases have a common denominator. A
      retrospective study of 120 subjects with laryngeal keratosis was examined. The
      intention of the Authors was to verify whether the principle risk factors
      involved in the appearance of laryngeal carcinoma were the same as those
      implicated in laryngeal keratosis formation. Sex age, work activity, cigarette
      smoke, alcohol consumption and vocal chord abuse were considered. Laryngeal
      keratosis takes keratosis with dysplasia as well as keratosis without. A link
      between these two types of keratosis and cancer was sought. In particular, the
      possibility that a persistent action of the mentioned risk factors could cause
      laryngeal dysplasia-free keratosis to change into dysplastic lesions and
      subsequently into cancer was investigated. A case-control study was performed in
      order to analyze the importance of work activity. Results were statistically
      significant (P < 0.001). The Cramer V2 calculation demonstrated a clear
      correlation between the number of cigarettes smoked and the appearance of
      dysplasia (V2 = 0.117; P < 0.005). Results showed a clearly different behaviour
      between sexes. The number of males was much higher than females as was the age at
      which keratosis appeared greater in males. The fact that the average age in which
      keratosis appeared preceded the appearance of laryngeal cancer by ten years
      indicates that this interrum is sufficient for keratosis with dysplasia to be
      transformed into cancer (due to the continued action of the mentioned etiologic
      factors, mainly referred to cigarette smoke). In our data analysis, no
      correlation was demonstrated between keratosis without dysplasia and cancer.

PMID- 8135098
TI  - [Carbon dioxide laser uvulopalatopharyngoplasty (UPPP). Part I. Surgical
      technique].
AB  - Snoring should not be regarded merely as a socially disruptive nuisance, but also
      as a potential risk factor of increased morbidity and mortality. Since numerous
      therapeutic approaches have been developed to treat snoring, the physician is
      faced with the dilemma of deciding which of the many possible treatments is the
      best for each snorer. Snoring is a sign of partial occlusion at the oropharyngeal
      level. Increased nasal airway resistance (NAR) may induce pharyngeal inspiratory
      collapse. Surgical treatment should be directed towards hindering pharyngeal
      collapse by surgical resection of redundant oropharyngeal tissue and/or surgical
      normalization of nasal resistance. Eighty-three consecutive patients suffering
      from snoring as major complaint together with nasal stuffiness were included in
      the study. Patients with OSA were excluded from the study. Increased nasal airway
      resistance (NAR) was a common finding in our population. Nasal surgery, involving
      both the external pyramid and nasal cavity, aimed at normalizing NAR was
      performed in 63 patients. In 15 cases, UPPP was performed contemporaneously or as
      a second surgical step. In 5 patients with no nasal abnormalities, pharyngeal
      surgery was the only surgical procedure. Personal variation of the classic UPPP
      is illustrated step by step in Part I. The procedure is carried out using the
      carbon dioxide laser, which offers several advantages both to surgeon and
      patient. The modified technique, which is associated with minimal morbidity,
      appears easy to standardize and successful in treating snoring. Results of the
      surgical procedures (nasal surgery and/or carbon dioxide laser UPPP) performed to
      treat snoring are reported in Part II.

PMID- 8135099
TI  - [Bisyllabic words for speech audiometry: a new italian material].
AB  - Bisyllabic words are the most frequently used italian speech material in
      evaluating intelligibility function. The italian words presently used are those
      proposed by Bocca and Pellegrini in 1950. The Lists of these words do, however,
      present some problems with regard to phonemic balance and word familiarity. In
      speech audiometry testing, Lists are considered interchangeable if each
      individual List has the same phonemic balance. So as to avoid incorrect
      identification due to incomprehension of infrequently used words, we chose 200 of
      the most familiar bisyllabic words from the most recent, widely used occurrence
      vocabulary of the Italian Language. Secondly, we proceeded with phonemic balance
      of the speech material. The selected words were divided into ten lists of 20
      words each, arranged in order to obtain the best phonemic balance within each
      individual List and among different Lists. The differences between the new and
      old speech material are presented and discussed.

PMID- 8135100
TI  - [Sudden deafness and acute synovitis: a case report].
AB  - A case of sudden deafness followed by arthritic manifestations is reported. The
      importance of immunologic tests, such as circulating immune complexes and the HLA
      system, in making a correct diagnosis is emphasized, which in turn suggests the
      possibility of establishing new diagnostic strategies.

PMID- 8135101
TI  - [Delayed endolymphatic hydrops: an analysis of 12 cases].
AB  - Delayed Endolymphatic Hydrops (DEH) is a clinical entity which is characterized
      by an early phase with a profound sensorineural hearing loss in one ear. After a
      prolonged period of time (from 1 to 68 years) a late phase of the disease appears
      with different otologic symptoms. The ipsilateral type of endolymphatic hydrops
      appears in the deaf ear with consequent episodic vertigo. The contralateral type
      develops symptoms of endolymphatic hydrop in the previously normal ear, with the
      onset of fluctuating hearing loss and/or episodic vertigo. This paper is a review
      of 12 cases of DEH (7 ipsilateral and 5 contralateral, age ranging from 19 to 79
      years). Diagnosis was established on the basis of clinical history and the
      results of audio-vestibular investigations, specifically designed to detect signs
      of endolymphatic hydrops (including the glycerol-test and neuroradiological
      imaging of the cerebello-pontine angle). In 8 patients the levels and frequency
      of anti-collagen I-II-IV-V, anti-laminin autoantibodies, complement, Ig and
      immuno-complexes were measured. Viral infections (measles, mumps, influenza) were
      thought to have caused the early phase in 6 cases. In the entire group of 12
      patients the delay between the onset of the ear loss and vertigo averaged 12
      years. In the group of the ipsilateral DEH, caloric tests showed in 5 cases a
      reduced or absent response of the deaf ear. About contralateral DEH, caloric
      tests showed bilateral reduced response in 2 cases, and, in 3 cases, a decreased
      response only in the previously normal ear. Regarding immunological study, an
      abnormal level of Ig and Complement was detected in 3 patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8135102
TI  - [Elaboration of a hearing disability scale].
AB  - On the basis of a previous pilot study a multiple-choice questionnaire about
      hearing disabilities was developed. The questionnaire (SDU) allowed 20 items. The
      answers were tailored to the single question and scaled in increasingly order of
      disability (form A) or in random order (form B). Modalities of administration
      (self-report or interview) and form (A or B) were randomized in a group of 123
      adult subjects with different degree of hearing impairment. Only one factor,
      attributable to hearing disability, was extracted by a factor analysis. This
      factor explains a major variance ratio of items related to speech perception in
      difficult listening context. A good correlation (r = .74) was found between SDU
      total score and hearing threshold in the better ear. No difference in mean score,
      variance and time of reduction of the SDU was found between form A and B. The
      Authors so propose the use of form A because of a more easy compute of the total
      score. Self-report was more time-consuming respect to interview (11.7' vs. 8.4').
      Furthermore, self-report was non possible in 13.8% of subjects for severe virus
      impairment and illiteracy and in 6.1% some form of support was necessary. No
      difference of mean score and variance between self-report and interview was
      found. SDU represents a tool for hearing disability evaluation useful in aural
      rehabilitation protocols. The principal advantage is high applicability thanks to
      short time required, simplicity of task and flexibility in the modality of
      administration.

PMID- 8135103
TI  - [Epistaxis and climatic events].
AB  - Data concerning daily climatic conditions in the area of Perugia during 1987-1990
      have been gathered and correlated to daily incidence of idiopathic nose-bleeding
      observed in the same area and during the same period (1064 patients on the
      whole). The aim was to verify the relation between climatic events and
      "epistaxis" phenomenon, relation that has been assumed since a long time but has
      never been scientifically demonstrated before. Following factors have been
      estimated: highest and lowest daily temperature, thermal gradient, atmospheric
      pressure and pressure gradient, relative humidity. Results of statistic
      correlations show that every climatic factors has a narrow range related to
      higher incidence of epistaxis and that nose-bleeding is likely conditioned by
      combination of critical values, as a low temperature with 4 degrees C daily
      gradient, a 716 mm Hg atmospheric pressure with 2 mm Hg negative gradient, a
      close to 100% relative humidity.

PMID- 8135104
TI  - [Rare manifestation of nasal polyposis in the Peutz-Jeghers syndrome].
AB  - We are relating a case of the Peutz-Jeghers syndrome, a disease characterized by
      hamartomatous polyposis and by mucocutaneous melanic pigmentation, in a rare
      variant identified by the presence of nasal polyposis. At the objective E.N.T.
      examination, the patient's nasal fossae were completely obstructed by translucid
      masses of a polypoid appearance and, moreover, a melanic pigmentation of the
      cutis, of the perilabial mucosa and of the oral cavity was encountered. At the X
      ray examination and, later, during the operation, also the right maxillary sinus
      appeared completely obstructed by polypoid masses. At the histologic examination,
      such polypoid neoformations were quite similar to common polyps of an
      inflammatory nature and, so, absolutely without any peculiar structural features.
      The nasal polyposis in patients suffering from the Peutz-Jeghers syndrome has
      been mentioned by Peutz since his first observation but it has been seldom
      described in the subsequent publications, even in relation to the presentation of
      rare causes to Congresses and Magazines of an exclusively gastroenterological
      interest, in which the main concern was that of identifying both the clinical and
      histological aspects of gastrointestinal hamartomatous polyposis and the
      correlation between the syndrome and the formation of malignant neoplasias in
      other organs to the prejudice of the secondary manifestations of the disease.
      Nevertheless, the nasal polyposis and, at any rate, the tendency to the formation
      of polyps in other districts (urinary tract, bronchi) are described among the
      less important features also in gastroenterological treatises of most recent
      publication. Clinical observations, even occasional, are completely missing in
      the E.N.T. ambit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135105
TI  - [Traumatic auricular hematoma in athletes: histopathological findings and
      clinical considerations on the experimental animal model].
AB  - Surgical procedures used for treating hematomas of the auricle are often
      defective in obtaining complete cosmetic and functional results when hematoma is
      of traumatic origin, as often thickening and deformity may outcome. Up to date,
      some pathological aspects of the healing process of auricular hematomas due to
      blunt trauma are still unclear as only lesions similar to spontaneous hematoma
      were experimentally produced and studied. Traumatic auricular hematoma, a lesion
      caused by rough contacts in sports like rugby, judo, karate, wrestling, etc., was
      never experimentally induced and studied. The Authors have induced both traumatic
      and non-traumatic hematomas in a group of 5 rabbits, injecting blood clots under
      the perichondral layer of one auricle while in the contralateral the hematoma was
      induced by compressive friction as it is caused during the above referred sports
      activities. Lesions of both sides were examined after 15 and 60 days and it was
      found that histopathological picture and clinical course of traumatic hematoma
      deeply differ from those of non-traumatic one. Non-traumatic lesion appears like
      a circumscribed hematoma without any evident sign of surrounding reaction, while
      traumatic lesion shows clear signs of polymorphic and marked reaction. In
      traumatic hematoma reactive and reparative processes are observed which alter the
      cartilage and perichondrium associated with many which alter the microhematomas
      in the subcutaneous connective tissue, close to the main hematoma. Histological
      findings found 2 months after injury show cartilaginous auricolar skeleton to be
      thickened by chondrocytes grouped in islands or fingered from
      perichondrium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135106
TI  - [The laryngo-tracheal reconstruction in the management of laryngo- tracheal
      stenosis].
AB  - Management of stenosis of the subglottic larynx remains one of the most
      challenging problems facing the laryngologist. This report describes our results
      treating severe subglottic stenosis. Five patients, 2 males and 3 females, with
      acquired stabilized laryngotracheal stenosis were treated during the period 1981
      1991. Ages ranged from 13 to 62 years. According to Cotton's classification the
      patients were assigned to a grade II-IV. The cause of the stenosis was trauma in
      two cases and intubation injury in three. All patients had a previously placed
      tracheotomy. All patients underwent a Laryngo-Tracheal-Reconstruction (L.T.R.);
      stenting was performed with a Montgomery type silastic laryngeal T-stent. The
      stent remained in place between 12 and 14 months. Four patients were decannulated
      and obtained a satisfactory airway. In one case granulation tissue in the
      reconstructed subglottis required a following Laser excision. In conclusion we
      can underline that, in our experience and on Literature reports, L.T.R. is a safe
      and effective procedure for severe crico-tracheal stenosis.

PMID- 8135107
TI  - [The randomized double-blind study of postoperative tonsillectomy pain control by
      muscle relaxants].
AB  - Tonsillectomy is accompanied by 7 to 14 days of pain. We entered 36 patients into
      a double blind placebo controlled study with dantrolene sodium, lioresal to
      evaluate modification of tonsillectomy pain and analgesic requirements after
      tonsillectomy. Patients were randomly assigned either dantrolene or lioresal or
      placebo orally four times a day for 5 days postoperatively. On a standardized
      questionnaire the patients recorded pain, activity level, analgesic requirements
      and side effects. We conclude that there is no significant differences in
      subjective pain or analgesic requirements between 3 groups. The muscle spasm is
      not the only factor of tonsillectomy pain. There is the association of other
      factors: nerve endings, individual sensitivity, local products of inflammation.
      In conclusion to control tonsillectomy pain we must use drugs with different
      action.

PMID- 8135108
TI  - [The treatment of ENT phlogosis: seaprose S vs. nimesulide].
AB  - In the present multicentre study, the antiphlogistic activity of seaprose S was
      assessed according to an experimental design of the controlled type versus
      nimesulide in patients with phlogistic pathology of ENT relevance and in patients
      undergoing otoiatric surgical operations. One hundred and sixty patients (87 M,
      73 F) were treated with seaprose S in 30 mg tablets (3tab/day) while 160 patients
      (95 M, 65 F) were treated with nimesulide in 100 mg (2 tab/day). The treatment
      lasted 7 days. At the beginning of the study, on the 3rd, 7th and 14th day
      (follow-up) the most significant signs and symptoms present in the pathological
      forms under consideration were evaluated. Common haematological and
      haematochemical laboratory parameters were also evaluated and any side effects
      occurring during the treatment were recorded. Considering the efficacy
      demonstrated, it was shown how the two drugs used possess an analogous action
      (NS) and are always able to exert positive control over the symptoms under
      examination. Administering seaprose S there were 9 cases of unexpected events
      (5.6%) while with nimesulide 26 patients (16.3%) showed problems of intolerance,
      with a highly significant statistical difference (p < 0.01) between the two
      groups. The analysis of the data obtained allows us thus to support the
      therapeutic use of seaprose S in the treatment of phlogosis of ENT relevance,
      since it has shown efficacy comparable to that of a NSAID such as nimesulide, but
      with greater safety.

PMID- 8135109
TI  - The placebo problem in child and adolescent psychiatry.
AB  - This paper is part of a special section on 'psychopharmacotherapy in children'.
      In contrast to adult psychiatry, research of placebo uses and effects in child
      and adolescent psychiatry is practically nonexistent, except in the context of
      clinical drug trials. Any type of therapy in pedopsychiatry may have positive or
      negative placebo effects, not only on the patients but also on their parents,
      teachers and therapists. The use of placebo in this population has controversial
      clinical, research, ethical and legal implications. Pedopsychiatrists should
      achieve consensus related to the clinical and research uses of placebo in their
      patients. Further research is needed to clarify the specific and nonspecific
      placebo factors related to short-term and long-term treatment outcome.

PMID- 8135110
TI  - Pharmacotherapy and behaviour therapy--competition or cooperation?
AB  - This paper is part of a special section on 'psychopharmacotherapy in children'.
      The latter may be combined with behavioural treatments, but in children only in
      the field of attention deficit hyperactivity disorder treatment studies has this
      combination been investigated and proved to be more effective than any single
      treatment alone. As to the treatment of depressive disorder, school phobia and
      obsessive-compulsive disorder in children and adolescents, no controlled
      empirical studies on combined therapies exist. Nevertheless, positive results
      from adult studies (e.g. depressive disorder, obsessive-compulsive disorder) may
      be, with some modification, paralleled in children and adolescents. So far, there
      are no indications that the combination of medication and behavioural treatment
      has antagonistic effects. Thus, we would make a plea for combining
      psychopharmacotherapy and behaviour therapy in child and adolescent psychiatry.

PMID- 8135111
TI  - The contribution of drug effects to the understanding of child psychiatric
      disorders.
AB  - The paper is part of a special section on 'psychopharmacotherapy in children'.
      Drugs not only help to treat symptoms successfully but may also help researchers
      and clinicians to gain a better understanding of the pathophysiology underlying
      these disturbances. This is exemplified in three child psychiatric disorders that
      exhibit disturbances in motor activity as a prominent symptom. These are general
      motor restlessness (ADHD), tic-disorder (sudden circumscribed motor actions) and
      stuttering (non-fluent speech). There is evidence that clinically useful drugs
      increase the cortical-subcortical interaction and tuning mechanisms providing the
      patients with a better self-regulation related to the motor performance.

PMID- 8135112
TI  - Theoretical aspects of the study of benzodiazepine receptors in infantile autism.
AB  - This paper is part of a special section on 'psychopharmacotherapy in children'
      and focuses on benzodiazepine receptors in autism. Infantile autism in an early
      and pervasive developmental disorder described by Kanner in 1943. Anatomical,
      pathological and magnetic resonance imaging studies have indicated changes in the
      cerebellum and hippocampus of autistic subjects. Given the numerical importance
      and diffuse benzodiazepine receptors, their study by functional brain imaging
      methods in vivo could be value in cases of infantile autism as a gauge of
      neuronal potentiality. The main data concerning benzodiazepine complex are
      presented. The relations between these data and the neurophysiological hypotheses
      of autism are discussed.

PMID- 8135113
TI  - Self-injurious behaviour (SIB)--from definition to human rights.
AB  - This article is part of a special section on 'self-injurious behaviour and
      autism' and is mainly based on a book edited by Luiselli, Matson and Singh (1992)
      addressing empirical data on self-injurious behaviour and mental retardation from
      a behavioural perspective. Within the overview of the book some information on
      autism is also presented and critically discussed. Self-injurious behaviour is a
      poorly understood phenomenon and problematic in many ways; its definition is not
      easy; little is known about the causes and neuroscientific models. Demographic
      data are scarce and functional analysis and interventions (behavioural
      techniques, medication, education) need to be further developed, under the
      protection of human rights committees.

PMID- 8135114
TI  - Autistic behaviour domains and their relation to self-injurious behaviour.
AB  - In order to find out if self-injury is associated with the autistic syndrome or
      at least to specific autistic behaviour patterns, 69 probands were examined and
      assessed according to the criteria of the Autism Diagnostic Interview according
      to IQ. We found a high prevalence of self-injurious behaviour among autistic
      individuals at age 4-5 but no positive correlation between self-injury and the
      different areas of autistic behaviour. Possible aetiological factors are
      discussed.

PMID- 8135115
TI  - Behavioural techniques to reduce self-injurious behaviour in children with
      autism.
AB  - This paper is part of a special section on 'self-injurious behaviour and autism'
      and concentrates on behavioural treatment techniques available and useful to
      reduce self-injurious behaviour in children with autism (e.g. extinction, time
      out, differential reinforcement, alternative forms of stimulation, sensory
      deprivation, physical restraint, crisis management, environmental modifications).
      It has become increasingly evident that the successful treatment of self
      injurious behaviour requires, first, a systematic and detailed (functional)
      analysis of the variables associated with the behaviour and, second, a hypothesis
      testing approach on an individual, naturalistic basis to increase the acquisition
      of alternative skills and self-control.

PMID- 8135116
TI  - Aggression and self-injurious behaviors in persons with autism--the TEACCH
      (Treatment and Education of Autistic and related Communications Handicapped
      Children) approach.
AB  - Aggression and self injurious behaviors are associated with some clients with
      autism and other forms of pervasive developmental disorder. These behaviors are
      not well understood, and treatment interventions are often ineffective. This
      article describes these behaviors in terms of the underlying deficits of autism,
      suggesting that interventions may be more effective if targeted at the underlying
      causes of the actions. The article presents behaviors and underlying causes
      within an "iceberg" conceptualization with visible behaviors depicted as
      occurring "above the water line" and hypothesized causes hidden "below the water
      line" of the iceberg. Examples of clinical cases are presented to illustrate the
      usefulness of the conceptualization.

PMID- 8135117
TI  - Educational management of self-injurious behavior.
AB  - This paper is part of a special section, on 'self-injurious behavior and autism'.
      Its focus is on the educational management of self-injurious behavior. The author
      describes, discusses and proposes an empirical methodology that may guide
      professionals in the description, analysis and monitoring of self-injurious
      behaviors in autism. A number of detailed case studies (guided by a seven-step
      intervention model) show that by teaching new competencies that override the
      needs expressed by challenging behaviors, patients with autism and self-injurious
      behavior may develop and affirm a better self-regulation of their lives.

PMID- 8135118
TI  - Psychopharmacological treatment of self-injurious behavior in individuals with
      autism.
AB  - This paper is part of a special section on 'self-injurious behavior and autism'
      and reports new data that variously support the suggested involvement of
      dopaminergic, serotoninergic and opiatergic neurotransmitter systems in the
      expression of self-injurious behaviour. Further, some notions concerning the
      underlying biological mechanisms of self-injurious behaviour related to brain
      function and brain topography are described. Finally, besides the critical
      evaluation of several drugs used to treat self-injurious behaviour, four cases of
      autism are reported where sulpiride, a benzamide derivative, clearly reduced self
      injurious behaviour.

PMID- 8135119
TI  - Functional diversity of central glutamate synapses--pre- and post-synaptic
      mechanisms.

PMID- 8135120
TI  - Myosin heavy chain isoforms in single fibres from m. vastus lateralis of soccer
      players: effects of strength-training.
AB  - The myosin heavy chain (MHC) composition of single fibres (n = 2171) was analysed
      with an electrophoretic technique in biopsy material from m. vastus lateralis of
      two groups of soccer players before and after a 3-month period of either strength
      (n = 8) or non-training (control) (n = 6). Traditional myofibrillar ATPase
      histochemistry demonstrated a decrease in type IIA fibres with strength-training
      (35.4 +/- 2.1 vs. 26.7 +/- 2.4% (P < 0.05)). This was not observed in the non
      training group (25.7 +/- 4.6 vs. 23.8 +/- 1.7%). One-dimensional electrophoresis
      on muscle homogenates showed no significant change in the amount of MHC isoforms
      in either of the two groups. The MHC isoform IIB was undetectable in all but
      three samples. No changes in the proportions of fibres containing any of the MHC
      isoforms were observed. Fibres containing only MHC isoform IIB were found in very
      small numbers (only 11 out of 2171). Before the experimental period, between 6
      and 10% histochemical type IIB fibres were found in both groups. This was
      identical with the proportion of fibres showing co-existence of MHC isoforms IIA
      and IIB, but in contrast to the very few fibres containing only MHC isoform IIB.
      This suggests that nearly all histochemical type IIB fibres of the soccer players
      display co-existence of both MHC isoform IIA and IIB. No major change in the
      muscle fibre area of the two groups was observed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8135121
TI  - Pattern of descending excitation of presumed propriospinal neurones at the onset
      of voluntary movement in humans.
AB  - The pattern of activation of presumed 'propriospinal' neurones was investigated
      in human subjects during phasic voluntary contractions of one of the following
      muscles: biceps, triceps, flexor carpi radialis (FCR), flexor carpi ulnaris (FCU)
      and extensor carpi radialis (ECR). Changes in the amplitude of the H reflex (FCR,
      ECR), or the tendon jerk (biceps, triceps) were used to assess the excitability
      of the corresponding motoneurone pools after conditioning stimulation.
      Conditioning stimuli were applied to the musculo-cutaneous, triceps and ulnar
      nerves. In most cases reflex facilitation was not observed at rest and was only
      disclosed at the onset of contraction. The characteristics of this facilitation
      (3-4 ms central delay, short duration, low threshold, depression when the
      afferent input was increased) are consistent with those previously attributed to
      'propriospinal' excitation. It is argued that the contraction-associated
      facilitation was descending in origin. The descending facilitation of the
      'propriospinal' system had a characteristic pattern in that the pathways selected
      by higher centres were those receiving the afferent feedback from the contracting
      muscle. These results provide further insight into the organization of human
      'propriospinal' pathways: (1) it is confirmed that afferents from each muscle
      activate a specific subset of neurones; and (2) it is suggested that the
      projections of each subset are divergent, implying that individual neurones
      project onto diverse motor nuclei, an organization that would favour the co
      ordination of multi-joint movements. Such an organization is discussed in
      relation to the possible role of the propriospinal system in the control of
      normal human upper limb movements.

PMID- 8135122
TI  - Effect of hypoxic hypoxia and ritanserin on capillary flow and oxygenation in
      rabbit skeletal muscle.
AB  - This study examined capillary flow and oxygenation in rabbit skeletal muscle
      during hypoxic hypoxia (inspired oxygen fraction = 0.10) and after administration
      of ritanserin (highly selective 5-Hydroxytryptamine-2-receptor antagonist).
      Capillary flow (hydrogen clearance) or oxygen pressure was measured with a
      multiwire micro-electrode which was placed on the surface of the left vastus
      medialis muscle. For measurement of regional microcirculatory blood flow a laser
      Doppler flowmeter probe was placed on the contralateral muscle. An experimental
      sequence with normoxaemia (arterial PO2 12.5 kPa), followed by hypoxaemia
      (arterial PO2 3.9 kPa) and thereafter sustained hypoxaemia (arterial PO2 4.0 kPa)
      during which ritanserin (0.035 mg kg-1 i.v.) was administered, was used. During
      hypoxaemia a decrease was seen in mean arterial pressure (MAP) by 27%, capillary
      flow by 25%, muscle oxygen pressure by 32% and laser-Doppler flowmetry (LDF) flow
      by 24%. After the administration of ritanserin the mean arterial pressure was
      further reduced by 7%, whereas the capillary flow increased by 59% and the muscle
      oxygen pressure by 31%. The LDF flow remained unchanged. These results
      demonstrate that, in this animal model, a decrease in skeletal muscle capillary
      flow and oxygenation during hypoxaemia can be reversed by the administration of
      ritanserin, despite a further reduction in blood pressure.

PMID- 8135123
TI  - In vivo effects of endothelin-2, endothelin-3 and ETA receptor blockade on
      arterial, venous and capillary functions in cat skeletal muscle.
AB  - This study describes, in quantitative terms, the effects of endothelin-2 and
      endothelin-3 on vascular tone (resistance) in large-bore arterial resistance
      vessels (> 25 microns), small arterioles (< 25 microns) and the veins, as well as
      on capillary pressure and fluid exchange in cat gastrocnemius muscle in vivo.
      Infusion of endothelin-2 or endothelin-3 (200-1600 ng kg-1 min-1, i.a.) elicited
      an initial transient dilation, followed by a dose-dependent, slowly developing
      constrictor response, being maintained after cessation of the infusion. At the
      dose of 400 ng kg-1 min-1 (n = 9), infused i.a. during 20 min, endothelin-2
      caused an average increase in total regional vascular resistance of 80%, and
      endothelin-3 of 35%, and the site of constrictor action of both peptides was
      preferentially located to the small arterioles. Endothelin-2 also constricted
      veins and, hence, evoked a pronounced capacitance response, whereas endothelin-3
      was devoid of any venoconstrictor effect. This difference, via effects on the pre
      /post-capillary resistance ratio, led to a more pronounced fall of capillary
      pressure in response to endothelin-3 than to endothelin-2. The new specific
      competitive ETA receptor antagonist, FR 139317, abolished the vasoconstrictor
      response to both endothelin-2 and endothelin-3 in vivo, whereas the preceding
      vasodilator responses were unaffected. These results, taken together with those
      of our previous analogous study of the effects of endothelin-1, indicated that
      all three endothelins were approximately equally as effective in eliciting the
      transient dilator response in skeletal muscle in vivo, whereas the order of
      vasoconstrictor activity was endothelin-1 > endothelin-2 > endothelin-3. Due to
      an especially pronounced venoconstrictor activity of endothelin-1, this peptide,
      in contrast to endothelin-2 and -3, evoked a rise in capillary pressure, with a
      consequent net transcapillary fluid filtration and muscle tissue oedema
      formation. The results further indicated that the vasoconstrictor responses to
      all endothelins in skeletal muscle were mediated by the ETA receptor, whereas the
      initial transient vasodilator responses seemed to be mediated by the ETB
      receptor.

PMID- 8135125
TI  - Modulation of neuroeffector transmission in guinea-pig pulmonary artery and vas
      deferens by exogenous nitric oxide.
AB  - Blockade of nitric oxide (NO) synthesis enhances contractile responses to
      transmural nerve stimulation in guinea-pig pulmonary artery, indicating
      neuromodulation by endogenous nitric oxide. In the present study, neuromodulatory
      effects of exogenous NO were examined in guinea-pig pulmonary artery and vas
      deferens. Application of NO as acid nitrite, to the guinea-pig pulmonary artery,
      inhibited the contractile response to transmural nerve stimulation as well as
      contractions to exogenous noradrenaline. The inhibition occurred in a dose
      dependent manner. Acid nitrite did not affect stimulation-induced release of
      [3H]noradrenaline in guinea-pig pulmonary artery. In the guinea-pig vas deferens,
      contractile 'twitch' responses to brief (25 pulses) transmural nerve stimulation
      and stimulation-induced release of [3H]noradrenaline was unaffected by acid
      nitrite. However, 'twitch' responses to prolonged stimulation were inhibited by
      acid nitrite, and tonic 'hump' responses were either enhanced or unaffected by
      acid nitrite. In conclusion, exogenous nitric oxide exerted an inhibition of
      adrenergic neurotransmission post-junctionally in guinea-pig pulmonary artery. In
      guinea-pig vas deferens, exogenous nitric oxide affected adrenergic and/or non
      adrenergic noncholinergic neurotransmission in a complex fashion, however without
      alteration in noradrenaline release. The data support a role for NO in modulation
      of neuroeffector transmission, especially by modulation of effector sensitivity,
      whereas modulation of noradrenaline release seems an unlikely role for NO in
      these and similar peripheral tissues.

PMID- 8135124
TI  - Adrenergic, cholinergic and VIP-ergic influence on gastric phasic motility in the
      rat.
AB  - We investigated the effects of adrenergic, cholinergic and vasoactive intestinal
      polypeptide (VIP)-ergic agonists and antagonists on the amplitude of gastric
      phasic contractions in the anaesthetized rat using a volumetric model. The
      amplitude of the phasic contractions was reduced significantly by atropine,
      hexamethonium or bilateral cervical vagotomy indicating that cholinergic neural
      activity involving both muscarinic and nicotinic receptors and intact vagal nerve
      function are integral parts of the control of basal gastric phasic motility. In
      contrast, neither selective alpha 1-, alpha 2- or non-selective beta-blockers had
      any significant influence on the amplitude of the gastric contractions suggesting
      that adrenergic neurones are not tonically active in the maintenance of basal
      phasic motility in the stomach. The amplitude of the gastric phasic contractions
      was, however, significantly reduced by the alpha 1-agonist L-phenylephrine, the
      alpha 2-agonist clonidine and a close intraarterial injection of VIP (3
      micrograms kg-1) but not be the selective beta 1-agonist, prenalterol, or the
      beta 2-agonist, salbutamol. These data suggest the presence of superimposed
      inhibitory control of phasic activity by VIP-ergic stimulation and by adrenergic
      neurones via alpha-receptor stimulation.

PMID- 8135126
TI  - Effects of blood-volume distribution on the characteristics of the carotid
      baroreflex in humans at rest and during exercise.
AB  - Seven supine subjects were studied at rest and during mild to moderate dynamic
      leg exercise with and without unloading of the cardiopulmonary baroreceptors
      accomplished by exposing the lower portion of the body to a subatmospheric
      pressure of 20 mmHg (Lower Body Negative Pressure, LBNP). The function of the
      cardiac branch of the carotid baroreflex was studied over its full operational
      range by measuring R-R intervals during application of pulse synchronous graded
      pressures (40 to -65 mmHg) in a neck-chamber device. Raising the carotid
      transmural pressure (systolic arterial pressure minus neck-chamber pressure)
      induced increasing R-R intervals in all conditions. In conformity with previous
      results from our laboratories it was found that the maximal rate of change in
      relative R-R intervals and the corresponding transmural pressure were higher
      during exercise than at rest, indicating that exercise increased the carotid
      baroreflex sensitivity and shifted its optimal buffering range to higher arterial
      pressures. LBNP did not affect the characteristics of the reflex at rest nor
      during exercise. It is concluded that reduced central venous pressure with
      consequent selective cardiopulmonary receptor disengagement exerts no influence
      on the carotid baroreflex control of heart rate (HR), as tested over the entire
      arterial pressure-effector response relation, either at rest or during mild
      moderate exercise.

PMID- 8135127
TI  - Thromboxane-like actions of prostaglandin D2 on the contractility of the rat
      colon in vitro.
AB  - Prostaglandin D2 (PGD2) concentration-dependently induced a contraction of the
      longitudinal muscle of the intact isolated rat colon in vitro. The effect of PGD2
      increased continuously from the anal to the oral end of the colon. The action of
      PGD2 was not inhibited but rather enhanced by the neurotoxin, tetrodotoxin, and
      by the PGD2 antagonist, AH 6809. In contrast, the thromboxane A2 antagonist, SK&F
      88046, concentration-dependently inhibited the PGD2 effect. The action of PGD2
      was mimicked by the stable thromboxane A2 derivative, carbocyclic thromboxane A2,
      indicating that PGD2 exerts its action on the smooth muscle by stimulation of
      thromboxane receptors. Between 18 (distal colon) and 38% (proximal colon) of the
      preparations exhibited spontaneous phasic myogenic contractions. The thromboxane
      antagonist, SK&F 88046, completely suppressed these spontaneous contractions. The
      combined lipoxygenase/cyclo-oxygenase inhibitor nordihydroguaiaretic acid and
      sulfasalazine mimicked the action of SK&F 88046, whereas the cyclo-oxygenase
      inhibitor, indomethacin, was ineffective. These results suggest that endogenously
      produced metabolites of arachidonic acid, e.g. thromboxane A2, contribute to the
      generation of spontaneous muscle contractions in vitro. The failure of
      indomethacin to suppress muscular activity, however, requires further studies.

PMID- 8135128
TI  - Postnatal development of functional dopamine, opioid and tachykinin receptors
      that regulate acetylcholine release from rat neostriatal slices. Effect of 6
      hydroxydopamine lesion.
AB  - In the present work we have studied the postnatal development of functional
      dopamine, opioid and tachykinin receptors, which regulate cholinergic activity in
      the neostriatum. The release of endogenous acetylcholine from rat striatal slices
      was measured using a chemiluminescent method. We have observed that the
      inhibition mediated by dopamine through D2 receptors was not detectable until
      postnatal day 10, whereas the inhibition mediated by opioid receptors was
      detectable at postnatal day 15 for delta-receptors ([D-Pen2,D-Pen5]-enkephalin)
      and at postnatal day 21 for mu-receptors ([D-Ala2,Gly(ol)5]-enkephalin).
      Excitatory effect mediated by tachykinins through NK1 ([Sar9,Met(O2)11]-
      Substance P), NK2 ([Nle10]-Neurokinin A4-10), or NK3 (senktide) receptors was
      already detectable at postnatal day 5. In order to examine the influence of
      dopamine in the development of tachykinin and opioid systems in the neostriatum,
      we induced dopamine deficiency by intraventricular injection of 6-hydroxydopamine
      at postnatal day 3. We observed an increase in senktide-evoked acetylcholine
      release at postnatal day 30. The effect produced by [Sar9,Met(O2)11]-Substance P
      and [Nle10]-Neurokinin A4-10 was not modified. Furthermore, at postnatal day 35,
      we could observed that the two opioid receptor agonists have no effect. Our
      results show that dopamine, tachykinins and opioids are already able to mediate
      the modulation of acetylcholine release in early stages of development with a
      different pattern of postnatal development. Furthermore, the integrity of a
      dopaminergic system plays an important role in the functional development of the
      neostriatal cholinergic neurons which are differentially modulated by opioids or
      tachykinins.

PMID- 8135129
TI  - Neuropeptides in dissociated cell cultures of mammalian spinal cord and dorsal
      root ganglion.
AB  - Immunohistochemical studies of leucine-enkephalin, somatostatin, vasoactive
      intestinal polypeptide and neurotensin were carried out in dissociated cell co
      cultures of embryonic mouse spinal cord and dorsal root ganglion, using the
      peroxidase-antiperoxidase technique. Leucine-enkephalin immunoreactivity exceeded
      that of the other peptides in these coculture preparations. Leucine-enkephalin,
      substance P and somatostatin were also studied in spinal cord cultures (without
      dorsal root ganglia) and in dorsal root ganglia cultures (without spinal cord).
      Each of these peptides was present in only a small percentage (< 10%) of
      perikarya and processes in spinal cord cultures. No leucine-enkephalin
      immunoreactivity was seen in dorsal root ganglion cultures; a considerable
      proportion of the processes were immunoreactive for substance P or somatostatin.
      These observations suggest that co-cultures of spinal cord and dorsal root
      ganglia can provide a simplified in vitro "model" of the nervous system for the
      study of peptidergic interactions.

PMID- 8135130
TI  - Butyrylcholinesterase activity in the developing auditory brainstem, the choroid
      plexus and the pituitary of the perinatal rat.
AB  - The butyrylcholinesterase activity in the vasculature of the brain, choroid
      plexus, and pituitary, was studied histochemically in rats during postnatal days
      1, 7, 14, 21 and 28. The brainstem auditory nuclei were used for comparison of
      vessels at different ages. We found intense butyrylcholinesterase activity in all
      intraparenchymal blood vessels, especially capillaries, in all ages. In the
      meningeal vessels, activity was especially prominent in 1 and 7 day old animals
      when the perineural meninges was relatively thick. In the pituitary, reaction for
      the enzyme was found in nonvascular elements, especially in the intermediate and
      posterior lobes. Vessels of the choroid plexus were associated with punctate
      regions of butyrylcholinesterase activity. These results do not support the
      suggestion of a major role for butyrylcholinesterase in the blood-brain barrier.

PMID- 8135131
TI  - A developmental study of lactate dehydrogenase isozyme and aspartate
      aminotransferase activity in organotypic rat hippocampal slice cultures and
      primary cultures of mouse neocortical and cerebellar neurons.
AB  - The development of enzyme activity and isozyme distribution of lactate
      dehydrogenase (LDH) was studied in murine organotypic hippocampal slice cultures
      and dissociated cultures of neocortical neurons and cerebellar granule cells and
      compared with that of the respective brain regions in vivo. In the hippocampal
      slice cultures and the hippocampus in vivo, the activity of aspartate
      aminotransferase (AAT) was also measured. During development in culture the
      specific activity of LDH increased in all types of cultures reaching values
      similar to that found in the corresponding brain areas in vivo. However,
      significant differences in the isozyme distribution were observed between the
      preparations in vitro and in vivo. During development in vivo, the LDH isozyme
      pattern changed from a preferential M-subunit composition to a preferential H
      subunit composition regardless of the brain area. This shift was not observed in
      the respective cultures where the M4-isozyme prevailed at all culture periods
      examined accounting for 30-45% of the total LDH activity. The cultured cerebellar
      granule cells did not express the H4-isozyme at all, while in the hippocampal
      slice cultures and the cultured neo-cortical neurons this isozyme accounted for
      about 5% of the total LDH activity. The activity of AAT in the hippocampal
      organotypic slice cultures increased considerably during the culture period in
      parallel with the increase in AAT activity during postnatal development of
      hippocampus in vivo. The activity of AAT in the slice cultures was, however,
      consistently lower than the corresponding activity in vivo.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8135132
TI  - Management of dizziness in primary care.
AB  - BACKGROUND: We sought to determine the types of dizziness problems that are
      commonly seen in primary care practices, and to bring to light clinical and
      demographic factors that predict management decisions. METHODS: We undertook a
      prospective cohort study with a 6-month follow-up using data gathered in nine
      primary care practices in two North Carolina counties. Subjects were 144
      dizziness patients examined by primary care physicians. Data collected included
      demographic characteristics, a standardized dizziness history, physician
      estimation of symptom severity and diagnostic certainty, and physician "worry"
      about arrhythmia, transient ischemic attack, and brain tumor. Physicians reported
      their management decisions and diagnosis (or differential diagnosis) by
      responding to a questionnaire after completing the patient encounter. A 6-month
      follow-up chart review and physician interview were completed on 140 patients
      (97.2 percent); information obtained included changes in diagnosis and patient
      mortality. RESULTS: The most common diagnoses were labyrinthitis, otitis media,
      benign positional vertigo, unspecified presyncope, sinusitis, and transient
      ischemic attack. The initial diagnosis changed during the 6-month follow-up
      period in 34 (24.3 percent) of patients. The overall course of these patients was
      benign, however, with only one death occurring during the 6-month follow-up
      period. Patients' dizziness tended to be managed using a combination of
      strategies, including office laboratory testing (33.6 percent), advanced testing
      (11.4 percent), referral to a specialist (9.3 percent), medication (61.3
      percent), observation (71.8 percent), reassurance (41.6 percent), and behavioral
      recommendations (15.0 percent). Office laboratory testing was associated with
      younger patient age, a suspected metabolic or endocrine disorder, and physician
      worry about a cardiac arrhythmia; advanced laboratory testing was associated with
      suspected cardiovascular or neurologic disorders. Medication tended to be
      prescribed for vertigo and severe symptoms and avoided when physicians were
      worried about a cardiac arrhythmia. Referral to a specialist was associated with
      suspected neurologic disease. Observation, behavior change, and reassurance were
      avoided in patients with poorly defined dizziness and tended to be used in older
      patients. The management approaches employed by the 4 physicians who referred the
      most subjects to the study varied considerably. CONCLUSIONS: Dizziness in primary
      care represents an extremely broad spectrum of diagnoses. The generally
      conservative management approach of primary care physicians in this study is
      consistent with basic clinical and epidemiologic principles, and patient
      mortality with this approach is low.

PMID- 8135133
TI  - Maternal fever during labor--what does it mean?
AB  - BACKGROUND: Several studies have shown maternal fever to be associated with
      chorioamnionitis and neonatal sepsis if at least two of the following five
      criteria are also present: maternal tachycardia, purulent or foul-smelling
      amniotic fluid, fetal tachycardia, uterine tenderness, or maternal leukocytosis.
      Less is known about the risk of neonatal sepsis when the presence of maternal
      fever in labor is the only criterion. METHODS: A retrospective medical record
      review searching for women who had a fever greater than 100.4 degrees F while in
      the active phase of labor during a 1-year period at the University of Michigan
      was undertaken to investigate the relation between isolated maternal fever in
      labor and neonatal sepsis. Eighty-two cases of maternal fever were found.
      RESULTS: Forty-six women met the clinical criteria for chorioamnionitis, and 6 of
      the 7 neonates with sepsis diagnosed were born to these mothers. There were no
      significant differences found in admission or intrapartum factors between women
      who did and did not meet clinical criteria for chorioamnionitis, and there was no
      association between these factors and neonatal sepsis. Epidural anesthesia was
      administered to 91 percent of these women and might be associated with maternal
      fever during labor. Using maternal clinical criteria for chorioamnionitis and a
      neonatal band cell-total neutrophil ratio of 0.2 or greater instead of the
      current system to determine the need for newborn antibiotic administration would
      improve the positive predictive value (12.5 percent versus 9.3 percent) and
      specificity (34.6 percent versus 16 percent) without compromising sensitivity
      (100 percent). All septic and probably septic newborns would be treated, and
      neonatal antibiotic administration would be reduced by 17 percent. CONCLUSIONS:
      The addition of the maternal clinical criteria for chorioamnionitis to the
      criteria already used for diagnosing and treating neonatal sepsis could prove
      useful in decisions regarding the selective administration of intrapartum
      antibiotics and prediction of risk of neonatal sepsis.

PMID- 8135134
TI  - Family practice residents' decision making regarding future practice of
      obstetrics.
AB  - BACKGROUND: This study assesses the attitudes of family practice residents toward
      their future practice of obstetrics. The decline of family practice obstetrics
      has resulted in problems of access to care for many areas. METHODS:
      Questionnaires were sent to 30 family practice residency programs and were
      distributed to 353 2nd- and 3rd-year residents; the overall response rate was 85
      percent. Respondents were asked to describe factors contributing to their
      decision whether to practice obstetrics. RESULTS: Seventy-two percent of the
      respondents indicated plans for future obstetrics practice. Reasons for choosing
      to practice obstetrics included personal interest, believing that obstetrics is
      an important part of family health care, and desire for diversity in practice.
      Primary concerns included interference with personal life, fear of lawsuits, and
      insurance premiums. Those deciding not to practice obstetrics cited interference
      with personal or professional life and desire for limited practice as deterrents.
      Important demographic variables predicting future practice included female sex,
      geographic location, and type of practice desired. CONCLUSION: This study
      portrays a resurgence in the percentage of family practice residents planning to
      practice obstetrics and discusses aspects of the training system that merit
      support to increase the number of family physicians providing obstetric care.

PMID- 8135135
TI  - Clinical approach to toxic mushroom ingestion.
AB  - BACKGROUND: This review provides the physician with a clinical approach to the
      diagnosis and management of toxic mushroom ingestion. It reviews the recent
      literature concerning proper management of seven clinical profiles. METHODS:
      Using the key words "mushroom poisoning," "mushroom toxicology," "mycetism,"
      "hallucinogenic mushroom ingestion," and "Amanita poisoning," the MEDLINE files
      were searched for articles pertinent to the practicing physician. Much of the
      original data were gathered at the Aspen Mushroom Conference held each summer
      throughout the 1970s at Aspen, Colorado, sponsored by Beth Israel Hospital and
      the Rocky Mountain Poison Center. Texts related to poisonous plants and specific
      writings concerning mushroom poisoning were also consulted; many of these texts
      are now out of print. RESULTS AND CONCLUSIONS: The 100 or so toxic mushroom
      groups can be divided into seven clinical profiles, each of which requires a
      specific clinical approach. Two of the seven groups (amanitin and gyromitrin)
      have a delay in onset of symptoms of up to 6 hours following ingestion and
      provide essentially all the major mobility and mortality associated with toxic
      mushroom ingestion. These two groups are the major focus of this review.
      Treatment of the potential mushroom ingestion, as well as guidelines for asking
      clinical questions, are included. These questions serve as a form of algorithm to
      assist the clinician in arriving at the correct toxic group.

PMID- 8135136
TI  - Bringing the special perspective of the family physician to the teaching of
      clinical ethics.
AB  - BACKGROUND: Medical ethics has traditionally been taught using dramatic, out-of
      the-ordinary cases to illustrate principles. Little attention has been focused on
      the ethical decisions family physicians make routinely in the course of their
      practice. METHODS: As part of a multidisciplinary course in medical ethics at the
      University of Washington School of Medicine, one class section was taught by a
      family physician using cases from her primary care practice. Cases were presented
      up to the point of decision making. Students were then encouraged to consider
      what action they would take. Each case was concluded with the family physician
      sharing the outcome of the case. RESULTS: Five case examples were presented. A
      comprehensive, context-sensitive approach to patient problems was modeled.
      Ethical issues explored included financial constraints, resource utilization,
      substance abuse, truth telling, confidentiality, and patient autonomy.
      CONCLUSIONS: Case-based teaching by a family physician was very effective at
      generating interest and enthusiasm among students and in encouraging their own
      thinking about ethical decisions. Students also valued the exposure to the family
      physician's style of practice. This teaching method created an excellent
      opportunity for learning about ethics and primary care that is applicable to many
      teaching settings.

PMID- 8135137
TI  - AIDS risk assessment in primary care.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) disease is a major cause of
      premature death in the United States. Primary care physicians can and should play
      an important role in its prevention. Detailed acquired immunodeficiency syndrome
      (AIDS) education, however, is not a cost-effective use of physicians' time for
      the great majority of patients, most of whom are at low risk for HIV infection.
      METHODS: Recommendations for AIDS prevention in the primary care setting were
      formulated based on a review of the published literature and on the author's
      personal experience as an AIDS epidemiologist and a practicing family physician.
      RESULTS AND CONCLUSIONS: Because risk for HIV infection is not uniform, primary
      care physicians can have the greatest impact by concentrating their prevention
      efforts on the minority of patients who are at high risk. This article proposes a
      30-second AIDS risk assessment for use in routine adult health care. Patients
      found to be at high risk should receive counseling on HIV risk reduction based on
      their individual needs. Also described are other situations when primary care
      providers should talk with their patients about AIDS prevention.

PMID- 8135138
TI  - Guidelines for the diagnosis and treatment of major depression.

PMID- 8135139
TI  - Primary care at a crossroads: progress, problems, and future projections.

PMID- 8135140
TI  - Chronic schizophrenia or meningioma?

PMID- 8135141
TI  - Practice guidelines for the management of vague patient complaints?

PMID- 8135142
TI  - Papanicolaou smear discrepancy: resolution by review.
AB  - BACKGROUND: Discrepancy between Papanicolaou smears and colposcopically directed
      biopsies often creates a treatment dilemma, especially when the cytologic
      specimen suggests a higher grade lesion than the histologic specimen. A method of
      side-by-side review using the Bethesda System was evaluated as a means of
      resolving this discrepancy between cytologic and histologic specimens. METHODS:
      By means of a retrospective chart review, we selected 150 patients undergoing
      colposcopic evaluation for abnormal cytologic findings. Thirty-eight patients had
      higher grade lesions on cytologic examination than on histologic examination.
      Twenty-four of these patients had both cytologic and histologic slides available,
      and these specimens were evaluated in a blinded review by a single pathologist
      using the Bethesda System of classification. RESULTS: Reevaluation yielded
      resolution of discrepancy in 19 of 24 cases, a 79.2 percent resolution.
      CONCLUSION: Review of cytologic and histologic specimens by an experienced
      pathologist using the Bethesda System can resolve many of the cases in which the
      cervical lesion is considered to be of a higher grade by cytologic examination
      than by histologic examination.

PMID- 8135143
TI  - Comparative studies on IL-6 production status in HTLV-1 chronically infected cell
      lines derived from different HTLV-1 associated pathologies.
AB  - We have comparatively studied the qualitative and quantitative status of
      Interleukin 6 (IL-6) production in several HTLV-1 chronically infected T-cell
      lines derived from patients suffering either of adult-T-cell leukemia/lymphoma or
      of tropical spastic paraparesis (TSP). Two other HTLV-1 chronically infected cell
      lines, coming from healthy seropositive carriers, were also analyzed. Our results
      demonstrate that, independently of the origin, all these T cell lines, as
      compared to uninfected HTLV-1 T cell ones, which were always IL-6 non producers,
      synthesize and yield comparable amounts of IL-6 synthesis, he nosological origin
      of infecting viral strains does not seem to play a differential role on IL-6
      qualitative or quantitative production parameters.

PMID- 8135144
TI  - GM-CSF production in human adenocarcinoma cell lines.
AB  - We describe the production of human granulocyte-macrophage colony-stimulating
      factor (hGM-CSF), by cell lines established from patients with different stages
      of breast, lung and colon adenocarcinoma. GM-CSF expression has been identified
      by immunocytochemistry determination, quantified on conditioned medium with
      specific ELISA procedure and evaluated by means of proliferation and
      differentiation of normal human monocytic and granulocytic progenitors. The
      growth of cell lines after incubation with exogenous GM-CSF and antibody-antiGM
      CSF was not modified. To better understand the patho-physiologic role of hGM-CSF
      in vivo we also estimated its serum levels at diagnosis in 75 patients with
      breast lung and colon adenocarcinoma and in 69 healthy person. Only two patients
      showed detectable GM-CSF levels. The lack of growth modulation observed in vitro
      with exogenous GM-CSF and antibody anti-GM-CSF suggests a non autocrine secretion
      by adenocarcinoma cells. The serum investigation evidences that the leukocytosis
      observed in adenocarcinoma patients is unrelated to a GM-CSF constitutive tumor
      production in vivo.

PMID- 8135145
TI  - Effects of granulocyte-macrophage colony stimulating factor on soluble
      interleukin-2 receptor serum levels and their relation to neopterin and tumor
      necrosis factor-alpha in cancer patients.
AB  - SIL-2R levels mainly depend on a T lymphocyte production. The mechanisms
      responsible for the elevated blood concentrations of SIL-2R in advanced solid
      tumors are still unknown. To investigate the role played by the monocyte
      macrophage system on SIL-2R release, we have evaluated serum levels of SIL-2R in
      10 head and neck cancer patients during GM-CSF subcutaneous administration (3
      mcg/kg/day for 11 consecutive days). Serum levels of TNF and neopterin, both
      produced by macrophages, were also measured. SIL-2R mean concentration
      significantly enhanced in response to GM-CSF, and their rise positively
      correlated to that in TNF and neopterin values, while lymphocyte mean number did
      not increase during the study. The present results represent the first in vivo
      demonstration that SIL-2R release is related to macrophage activation, rather
      than to depend only on lymphocyte proliferation.

PMID- 8135146
TI  - BQ-123 inhibits both endothelin 1 and endothelin 3 mediated C6 rat glioma cell
      proliferation suggesting an atypical endothelin receptor.
AB  - The mitogenic action of endothelins (ETs) 1 and 3 was studied on C6 rat glioma
      cells in serum-free culture conditions. In order to characterize the ET receptor
      subtype involved in this effect, BQ-123, and ETA receptor selective antagonist
      was used. Our results confirmed that both ET-1 and ET-3 are mitogenic peptides
      for C6 cells and demonstrated for the first time that the ETA receptor antagonist
      BQ-123 inhibits the proliferative effect of both ET-1 and ET-3 in this cellular
      system, providing evidence of an atypical ET receptor on C6 cells.

PMID- 8135147
TI  - Heterogeneity of the alpha-interferon-mediated overexpression of class-I and
      class-II major histocompatibility complex molecules in primary cultured cancer
      cells.
AB  - Human alpha- and gamma-interferons (IFNs) have the capability of enhancing the
      expression of major histocompatibility complex-class I and class II (MHC-I and
      MHC-II) as well as other surface tumor associated antigens (TAA) on cancer cell
      lines. This capability, associated to the anti-proliferative effect observed both
      in vitro and in vivo, was the basis of the extended use of IFN in cancer
      patients. Despite the great expectations, several solid neoplasms resulted
      resistant to treatment with IFNs. In order to analyze the actual effects of IFNs
      on cancer, we treated primary cultures of different histotypes of cancer cell,
      which are well known to differ significantly from established cell lines, with
      escalating doses of alpha-IFN. In this paper, we demonstrate that a variable
      proportion of culture was able to potentiate the expression of MCH-I and MCH-II
      molecules on the surface. This finding suggests that a clear functional
      heterogeneity was present in primary cultures of cancer cells, that strictly
      reflected the in vivo situation. In addition, it is of note that in some
      histotypes, "natural" lymphoblastoid alpha-IFN was more effective than
      recombinant human alpha-IFN in the induction of this capability.

PMID- 8135148
TI  - [Opioid dependence and word learning].
AB  - We study the influence of the drug use story of polydrug users which use heroin
      as a principal drug in learning a new material. We assess the learning of a list
      of words in 31 heroin users and we compare their performance with a group of 31
      non drug users with the same personal and sociocultural characteristics. The
      obtained results show an impairment in the performance of drug users which not
      depend of the length of addiction, abstinence, and either the presence of a
      polydrug use.

PMID- 8135149
TI  - [Familial rituals: general aspects and their use in clinical practice].
AB  - Family rituals are described in this article and clinical examples are given on
      these types: Of belonging, curative and normative. Family rituals should be
      considered as a diagnostic and therapeutic instrument.

PMID- 8135150
TI  - [The feminine role as a determinant of mental health among the women of the
      general population of Cantabria].
AB  - This paper tries to analyse the relationship between traditional feminine role
      (marriage, motherhood and housing) and mental health in spanish women. The
      General Health Questionnaire 60-items (GHQ-60) was used to define "cases" in a
      random sample of the general population of Cantabria consisting of 630 women aged
      17 and over. The rate of probable prevalence of psychiatric disorders was 26.4%.
      In contrast to previous studies, motherhood and traditional feminine role
      correlated with the lowest GHQ-60 mean scores. Occupational status was not
      related to mental health. Women living with husband, children, parents and/or
      parents-in-law scored lower on GHQ-60 than those living with husband and
      children. These results are discussed in the light of previous findings in the
      literature. At least, they reconfirm the importance of socio-cultural factors in
      community psychiatric disorder.

PMID- 8135151
TI  - [Personality disorders in patients with eating disorders: a controlled study].
AB  - A group of 24 eating-disordered female subjects (10 anorexia nervosa--AN--and 14
      bulimia nervosa--BN--patients) were interviewed, using a semistructured interview
      for DSM-III-R Axis-II Personality Disorders (SCID-II). A group of 54 subjects
      without eating disorder acted as a control group. A high rate of personality
      disorder (PD) diagnoses occurred in eating disordered subjects (AN and BN
      patients), with a high prevalence of borderline, dependent, and self-defeating
      PD. Avoidant and obsessive-compulsive PD were more common in AN patients, whereas
      BN was associated with histrionic PD. Findings have implications for the
      assessment and diagnosis of eating-disordered patients and for treatment
      planning.

PMID- 8135152
TI  - [Factors implicated in the "routes of care" in mental health].
AB  - We analyze in this paper the way in which different sociodemographic and clinical
      factors influence, in different health areas of Cantabria (Spain), the pathways
      taken for patients suffering from "new psychiatric illness". The work is part of
      a Multicentric International Research Project developed by the World Health
      Organization aimed at evaluating and improving the quality of mental health care
      in different centres of the world. The general pathway to mental health services,
      in Cantabria, is dominated by the general practitioner (54.3%) and by the
      "hospital doctor/medical specialist" (26.4%), been therefore similar to the one
      found in other Spanish speaking centres, like Granada and Cuba; the differences
      are, however, much larger with the one found in Mexico city. It is also, possible
      to observe in our data that the pathways are influenced by clinical factors,
      among which the more relevant one is one related to the characteristics of the
      psychopathology. Thus in general we found that two factors like, the presence of
      "psycho-organic" syndromes and the severity of the psychopathology appears to
      influence: i) the degree of complexity of the pathway, which is higher in the
      "psycho-organic" and in the more severe forms of psychiatric disorders; ii) the
      protagonist which assumes, in detriment of the general practitioner, other
      "helping agencies" which is also increased in the "organic" and more severe
      disorders. We also found that other aspects like: the act of establishing
      "contact" with services, the delay in the obtention of help, and the prescription
      of psychotropic medicines, were also influenced by different sociodemographic,
      clinical and service related variables.

PMID- 8135153
TI  - [Life events and self-destructive behavior].
AB  - The role of life events in precipitating self-destructive behaviour, especially
      in suicide attempts, needs to be studied in this paper the social readjustment
      rating scale (Holmes and Rahe), in its spanish version, in a sample of 100
      suicide attempters are reported. The mean social readjustment index was 255.2 +/-
      137.01, which is a higher score than that observed in medical inpatients (180.69
      +/- 72.03) in our context. The mean life events index was 8.69 +/- 4.32, higher
      valves than were recorded in the somatic in patients sample (5.97 +/- 2.99). No
      sex differences were found in any of the two indexes. The finding of a greater
      number of unpleasant life events by different researchers is discussed.

PMID- 8135154
TI  - Educational placement and residential schools.

PMID- 8135155
TI  - Minority and minority-deaf professionals. How many and where are they?
AB  - A survey of 6,043 professionals in 349 deaf education programs showed that 10.4%
      are from nonwhite or minority ethnic/cultural backgrounds. Of these minority
      professionals, 11.7% are deaf. Only 8 minority deaf administrators were found.
      Chi-square analyses showed that ethnic/cultural background and hearing loss were
      strongly associated with the type of program where the professionals were
      employed. More than half of the minority professionals worked in public schools.
      The District of Columbia, New York, and Maryland lead the country in the number
      of deaf professionals employed. More than half of all black deaf professionals
      work in either D.C. or New York. Texas leads the country in numbers of Hispanic
      professionals employed, and New Mexico has more Hispanic professionals than does
      California, New York, or Florida.

PMID- 8135156
TI  - Constructing meaning from narrative text. Cognitive processes of deaf children.
AB  - The purpose of this study was to examine the reading comprehension processes of
      deaf children during the reading of narrative text by exploring the predictions
      they made when the material confirmed and did not confirm their expectations. The
      subjects were 48 deaf children in upper elementary and junior high school. Each
      read a well-formed and non-well-formed story, half of which began with a thematic
      organizer. They were asked to make predictions at three points in each story. It
      was found that (1) when the children made elaborated predictions, they tended to
      make them with both stories, (2) elaborated predictions were related to reports
      of mental imagery, and (3) more elaborations were reported near the beginning and
      end of non-well-formed stories and stories with no organizers.

PMID- 8135157
TI  - Research-based language intervention strategies adapted for deaf and hard of
      hearing children.
AB  - Strategies found to facilitate the language development of young, hearing
      children are reviewed in this paper, and adaptations and examples for use with
      deaf and hard-of-hearing children are provided as alternatives to simply advising
      professionals and parents to increase the quantity of conversation with these
      children. It is suggested that adults accelerate the language acquisition of deaf
      and hard-of-hearing students by capitalizing on the linguistic opportunities
      provided in particular environments, rearranging environments, being responsive
      to indications that children have comprehended messages and are open to risk
      communication, and specifically by intervening on form, content, and use skills.
      The author challenges professionals to document empirically the usefulness of
      each language intervention technique presented here.

PMID- 8135158
TI  - Outreach. The resource of state schools for the deaf.
AB  - Sixty-five state supported schools for the deaf were surveyed to obtain basic
      data on the provision of statewide outreach services. Fifty schools (77%)
      responded, 41 (82%) of which were engaged in statewide outreach. Twelve states
      are authorized by statute, 13 by interagency or memorandum of agreement with SEAs
      (State Education Agency) or LEAs (Local Education Agency). Sixteen states have
      undertaken these efforts independently or under less formal arrangements. Funding
      varies--some receive state or federal funds, others include such services as part
      of their regular budgets. The data contained herein should be valuable to schools
      and states wishing to become "partners" in the education of deaf children.

PMID- 8135159
TI  - Psychological evaluation of adults in a cochlear implant program.
AB  - Relatively few papers have been written about the psychological evaluation of
      cochlear implant patients, compared to the number of reports on surgical and
      audiological aspects. Formal and informal psychological assessment are an
      integral part of the cochlear implant program at Manchester and contribute to
      team decisions about the suitability of patients for implantation. The
      psychologist also monitors the subsequent progress of recipients. This paper
      describes the major reasons for carrying out psychological evaluations of
      prospective recipients and for monitoring their psychological status. The main
      assessment techniques used in the Manchester program are outlined. Group findings
      from the initial assessments of the first 40 cochlear implant patients (including
      five deaf-blind patients) are also reported.

PMID- 8135160
TI  - Screening procedures used to identify children with hearing loss.
AB  - This study focused on the hearing-screening procedures used to identify children
      who have hearing losses who were later enrolled in SKI*HI parent/infant programs
      throughout the country. Responses to a questionnaire for 1,404 children indicated
      that although auditory brainstem response (ABR) technology provided the lowest
      mean identification age, informal hearing-screening procedures (parental
      suspicion and referral) were the procedure of identification for 80% of the
      children. The data suggest that formal screening programs are not presently
      locating the vast majority of infants who have hearing losses. Recommendations
      for professional and parental education in the area of hearing-loss screening are
      provided.

PMID- 8135161
TI  - A longitudinal study of intellectually gifted deaf and hard of hearing people.
      Educational, psychological, and career outcomes.
AB  - Fifty-seven gifted deaf and hard of hearing people were followed longitudinally
      to determine their current educational, career, and mental health status. Of the
      49 who were old enough for postsecondary schooling and for whom data were
      available, 86% attained some postsecondary education. Of these, 43% graduated
      from a four-year college and 18% attended graduate school. Of the 57 total cases,
      39% experienced mental illness of a severity requiring either inpatient
      hospitalization or outpatient therapy. Occupationally, 33% of the total sample
      were in professional or supervisory roles, 18% were technicians or craftspeople,
      and a surprising 30% were unemployed. People with progressive and late-onset
      hearing losses had especially severe problems of adjustment and employment.
      Demographic data and a further breakdown of the above information are provided.

PMID- 8135162
TI  - Reading comprehension of deaf readers. The impact of too many or too few
      questions.
AB  - Reading comprehension need not be considered to be an elusive construct; for most
      readers, nonclinical reading problems can be viewed simply as a process
      influenced by readers' questions. Most reading comprehension difficulties of deaf
      readers can be addressed in a straightforward and effective manner once it has
      been determined whether the reader has too few or too many questions while
      reading. This article explains the relationship between the number and type of
      questions deaf readers have and their comprehension of the reading material. It
      also describes intervention strategies that can be used to improve comprehension.
      The article is intended for teachers and other professionals who work with deaf
      students, deaf adults who have reading problems, and parents who have a deaf
      child with a reading problem.

PMID- 8135163
TI  - Chinese medicine in Malaysia and Singapore: the business of healing.
AB  - Traditional Chinese medicine as it persists in several East and Southeast Asian
      countries, has undergone major changes. Such changes have reinforced the trading
      aspects of traditional Chinese medical practice with relatively little advantage
      for the medical care component. This paper examines the nature of changes in
      contemporary ethnic Chinese medical practice in Malaysia and Singapore with the
      aim of understanding their implications for the persistence of this medical
      tradition.

PMID- 8135164
TI  - Effect of acupuncture at the right Hoku point on bilateral vibration-induced
      finger flexion reflex in man: comparison between in-situ and Sparrow Pecking
      technique.
AB  - The purpose of this study was to compare the effect of the Sparrow Pecking (SP)
      technique with that of the In-Situ (IS) technique of acupuncture on vibration
      induced finger flexion reflex (VFR). Subjects were 30 healthy adults. VFR,
      flexion movement of the vibrated finger, was induced by vibrating the volar side
      of the middle finger tip. The acupuncture point was the right Hoku point. Both
      techniques of acupuncture inhibited VFR in the ipsilateral and contralateral
      sides, but inhibition with SP was significantly greater than that with IS
      (percentage control force of VFR, mean +/- SD: with SP right, 62.1 +/- 24.6%,
      left, 60.6 +/- 27.9%, with IS right, 74.9 +/- 26.6%, left, 78.1 +/- 29.5%, P <
      0.0005). The results suggest that SP suppresses facilitation of VFR in the reflex
      arcs more than IS does.

PMID- 8135165
TI  - Differences in acupuncture point SP-10 and non-acupuncture point following
      subcutaneous injection of Tc-99m pertechnetate.
AB  - A new method of radionuclide venography, namely SC-RNV, by subcutaneous injection
      of Tc-99m pertechnetate at acupuncture points was recently developed in our
      laboratory. The time-activity curve of SC-RNV can be divided into 3 phases as:
      the phase of diffusion of radioisotopes through the subcutaneous space, the phase
      of entrance of radioisotopes into intravascular space to reach a peak
      concentration and the phase of equilibrium state of radioisotopes in the
      intravascular space. In this study, we used the 3 phases of SC-RNV to evaluate
      the absorption of Tc-99m pertechnetate injected subcutaneously in the acupuncture
      point SP-10 (Xuehai) and in a non-acupuncture point near SP-10. The results
      revealed that the absorption of Tc-99m pertechnetate via SP-10 was significantly
      greater than that of non-acupuncture point, evidenced by shorter phase 1, higher
      peak activity and greater accelerating rate of phase 2. This suggests that the
      absorption of radioisotopes from acupuncture point is faster and greater than
      that of non-acupuncture point.

PMID- 8135166
TI  - Long-term outcome of acupuncture in women with frequency, urgency and dysuria.
AB  - Urodynamic measurements including cystometry, anal sphincter electromyography,
      urethral pressure profilometry and uroflowmetry were carried out on 21 female
      patients before acupuncture and at 1 and 3 years during follow-up. Follow-up
      ranged from 60 to 72 months (average 66.2 months). There was no significant
      difference in all urodynamic measurements before acupuncture and at the 1 year or
      3 years follow-up. During follow-up, acupuncture at the Sp-6 point was performed
      in patients who had recurrence of symptoms of frequency, urgency and dysuria. The
      number of acupuncture treatments ranged from 2 to 8 times, with an average number
      of 4.8 times. A decrease of acupuncture treatments after 30 months was noted on 8
      patients, but it was not statistically significant. We concluded that the long
      term outcome of acupuncture at the Sp-6 point for women with frequency, urgency
      and dysuria was positive, but that the effect was temporary and repeated
      acupuncture was necessary to maintain beneficial effects.

PMID- 8135167
TI  - Protection by moxibustion against experimental hyperbilirubinemia and cholangitis
      in rats.
AB  - The effects of moxibustion on experimental hyperbilirubinemia and cholangitis
      were studied in male rats (n = 33). The experimental group were treated with
      moxibustion, 18, 12 and 6 hours prior to and 6, 12 and 18 hours after challenge
      with oral alpha-naphthylisothiocyanate (ANIT, 100 mg per kg). Rats were
      sacrificed 48 hours after challenge. Serum and liver samples were taken for
      biochemical and histological analysis, respectively. The results revealed that
      rats treated with ANIT exhibited elevations in bilirubin, SGOT and SGPT as well
      as cholangitis. In rats receiving moxibustion and ANIT, biochemical and
      morphological parameters of liver injury were significantly reduced. Thus, this
      study shows that moxibustion therapy may be able to prevent ANIT-induced
      hyperbilirubinemia and cholangitis.

PMID- 8135168
TI  - An observation on flash evoked cortical potentials and Qigong meditation.
AB  - The purpose of this study was to investigate the functional state of the cerebral
      cortex during Qigong meditation with flash visual evoked potentials (F-VEPs)
      recorded from the occipital scalp in four groups of adults. The first group
      included 14 subjects who had exercised in Neiyang Gong for 0.5-5.5 years. The
      second group was composed of 12 subjects who had practiced Neiyang Gong for only
      0.5-3 months. Eleven subjects who had never practiced Qigong before made up the
      third group and served as control. Eleven Qigong practitioners constituted the
      fourth group. It was found that F-VEP amplitudes were increased in the first
      group and decreased in the fourth group with the exception of one subject during
      Qigong meditation. No significant changes were found in the second group and
      controls. The results were discussed and it is shown that Qigong mediation may
      have either facilitative or inhibitory effects on the visual cortex depending on
      the Qigong methods practiced by different individuals.

PMID- 8135169
TI  - Effects of kami-kihi-to (jia-wei-gui-pi-tang) on autoantibodies in patients with
      chronic immune thrombocytopenic purpura.
AB  - We studied the effect of Kami-kihi-to (Jia-Wei-Gui-Pi-Tang) on the production of
      autoantibodies in ten patients with chronic immune thrombocytopenic purpura.
      After administration of Kami-kihi-to, platelet count was increased in seven of
      the ten patients (p < 0.05). Using Western blotting, we demonstrated the
      disappearance of autoantibody reaction with antigen in one patient. However,
      platelet-associated IgG was decreased in eight of ten patients (p < 0.05). Kami
      kihi-to appears to promote the suppression of autoantibodies in patients with
      chronic immune thrombocytopenic purpura. No side effects were observed in any
      patient. Thus, Kami-kihi-to may be a useful and safe drug in the management of
      chronic immune thrombocytopenia purpura.

PMID- 8135170
TI  - The effects of Chinese herbs on improving survival and inhibiting anti-ds DNA
      antibody production in lupus mice.
AB  - Systemic lupus erythematosus (SLE) is an important autoimmune disease with
      multiple organ system involvement. From preliminary studies, we have found that
      six Chinese herbs: Atractylodes ovata, Anqelica sinensis, Cordyceps sinensis,
      Liqustrum lucidum, Codonopsis pilosula and Homo sapiens can improve defective in
      vitro interleukin-2 (IL-2) production in patients with SLE. In order to
      investigate the in vivo effects of these herbs, we used NZB/NZW F1 mice, a
      typical lupus animal model used to test these herbs. It was found that C.
      pilosula, H. sapiens and C. sinensis could prolong the life span of female
      NZB/NZW F1 mice and inhibited anti-ds DNA production. Although A. sinensis could
      prolong the life span of experimental mice, it did not inhibit the production of
      anti-ds DNA antibody. These herbs may have great potential for the management of
      human SLE in the future.

PMID- 8135171
TI  - Suppression of spontaneous development of uterine adenomyosis and mammary
      hyperplastic alveolar nodules by Chinese herbal medicines in mice.
AB  - The effects of traditional Chinese herbal remedies, Shakuyaku-kanzo-to (SKT) and
      Hachimijiou-gan (HJG), on the spontaneous development of uterine adenomyosis and
      mammary hyperplastic alveolar nodules (HAN) were examined in an experimental
      animal model using SHN strain of mice. Female mice were provided with the chow
      containing 1% of SKT or HJG during 25-150 days of age. At 150 days of age, SKT
      treatment showed significantly lower incidence of adenomyosis, and HJG treatment
      resulted in a significantly lower incidence of HAN when compared to a control
      chow containing no medicines. Long-term exposure to these herbal medicines
      affected little serum prolactin (PRL) level, estrous cycle, food intake and body
      growth. Thus, the present mouse data suggest that the oral administration of
      these herbal medicines is a useful tool for the treatment of uterine adenomyosis
      or mammary disorder such as cystic mastitis.

PMID- 8135172
TI  - Effects of jen-sheng-yang-yung-tang on cellular immunocompetence of gamma
      irradiated mice.
AB  - This study was conducted to determine the therapeutic effects of Jen-Sheng-Yang
      Yung-Tang on mice irradiated by gamma-ray. A total of 160 male ICR strain mice, 6
      7 weeks of age, were chosen to receive different treatment of radiation and Jen
      Sheng-Yang-Yung-Tang. After the treatments, six to eight mice from each group
      were sacrificed on days 1, 5, 12, 19, 26 and 33. The body and splenic weights of
      mice by different treatments were measured and the splenic cells were separated
      under aseptic conditions, thereafter. The changes of cellular immunocompetence in
      mice following treatments were measured by 3H-thymidine incorporation in each
      experimental mouse. The results revealed that 4 Gy of gamma-ray irradiation
      inhibited the increases of body and splenic weights and exerted an obvious
      inhibitory effect on the blastogenic responses of the splenic lymphoid cells
      after being stimulated by mitogens such as PHA, Con A, PWM and LPS. Jen-Sheng
      Yang-Yung-Tang administration seemed to help the recovery of cellular
      immunocompetence in the gamma-ray irradiated mice. Among these treatments, Jen
      Sheng-Yang-Yung-Tang administered with the concentration of 20 mg/20 g body
      weight after irradiation enhanced the recovery of radiation damages and had the
      highest efficacy of any other kinds of treatments.

PMID- 8135173
TI  - The effects of ninjinyoeito on human vascular endothelial cells.
AB  - The effects of Ninjinyoeito on endothelial cells from a human umbilical vein were
      examined. As a result, the maximum cell density obtained after the addition of
      Ninjinyoeito was found to be 400 ng/ml, and its inhibitory effect on the
      development of endothelial injury was also observed. In addition, the levels of
      LDH and Al-p, which are parameters decreasing with aging, were significantly
      high. Judging from these results, Ninjinyoeito presumably exerts an anti-aging
      effect by inhibiting the metabolic aging of cells.

PMID- 8135174
TI  - Traditional medicinal plants of Saudi Arabia.
AB  - The work gives an account of the use of twenty plant species in Saudi traditional
      medicine and their main chemical constituents. The botanical name, local name or
      names (in Arabic language), family, mode of administration and voucher herbarium
      numbers are recorded. Such a study is not only to document the current status of
      traditional uses of medicinal plants in Saudi Arabia, but also to give awareness
      of possible new drug resources.

PMID- 8135175
TI  - Tissue sampling in the era of cost constraints.

PMID- 8135176
TI  - Autologous blood donation. How much is enough?

PMID- 8135177
TI  - Sampling of radical prostatectomy specimens. How much is adequate?
AB  - Prostate glands from 52 patients with clinical stage B carcinoma were examined
      using two sampling techniques. After fixation and conization of the apical
      portions, each gland was serially sectioned with sections mounted whole on
      oversized glass slides and examined for pathologic features of prognostic
      importance. A second examination was subsequently conducted on the same tissue
      using only alternate sections. No differences in tumor type, grade, Gleason
      score, multiplicity, or capsular penetration were detected in 75% of cases. The
      discrepancies that did occur were most often minor variations in multiplicity and
      Gleason score. Of the 20 glands with capsular penetration observed with the
      serial sectioning method, 17 (85%) were detected using alternate sectioning. The
      surgical margin was involved in two of the three invasive foci that would have
      been missed. Although the topography is better displayed, the authors'
      examinations indicated no significant advantage to whole mount sections compared
      with sections mounted on standard-sized glass slides. Considering the most
      effective use of resources, as well as the current modalities available for
      patient monitoring, the results support the use of an alternate sectioning method
      for pathologic examination of specimens removed for clinically localized prostate
      cancer.

PMID- 8135178
TI  - Performance analysis of manual and automated systemized nomenclature of medicine
      (SNOMED) coding.
AB  - Many pathology departments rely on the accuracy of computer-generated diagnostic
      coding for surgical specimens. At present, there are no published guidelines to
      assure the quality of coding devices. To assess the performance of systemized
      nomenclature of medicine (SNOMED) coding software, manual coding was compared
      with automated coding in 9353 consecutive surgical pathology reports at the
      Baltimore Veterans Affairs Medical Center. Manual SNOMED coding produced 13,454
      morphologic codes comprising 519 distinct codes; 209 were unique codes (assigned
      to only one report apiece). Automated coding obtained 23,744 morphologic codes
      comprising 498 distinct codes, of which 129 were unique codes. Only 44 (.5%)
      instances were found in which automated coding missed key diagnoses on surgical
      case reports. Thus, automated coding compared favorably with manual coding. To
      achieve the maximum performance, departments should monitor the output from
      automatic coders. Modifications in reporting style, code dictionaries, and coding
      algorithms can lead to improved coding performance.

PMID- 8135179
TI  - Application of the Scarff-Bloom-Richardson tumor grading system to fine-needle
      aspirates of the breast.
AB  - Assigning a tumor grade to breast cancers provides important prognostic
      information. This study evaluated the applicability of the Scarff-Bloom
      Richardson (SBR) breast cancer grading system to aspiration biopsy cytology.
      Thirty-five consecutive breast cancer fine-needle aspirates and their surgical
      specimens were reviewed by two pathologists. An SBR grade of 1-3 was assigned by
      each pathologist to both the fine-needle aspirate and biopsy specimen, based on
      the sum of scores given to each of three features: tubular differentiation,
      nuclear pleomorphism, and mitotic index. Both pathologists assigned the same SBR
      score to 74.3% of biopsy specimens and 65.7% of fine-needle aspirates. The
      cytologic grade could be used to predict the histologic grade in as many as 57.1%
      of cases. The wide disparities in the cytologic and histologic grades in some
      cases were chiefly due to difficulties in detecting mitoses or tubules in the
      cytology.

PMID- 8135180
TI  - Crystalloids in metastatic prostatic adenocarcinoma.
AB  - The authors report a case of metastatic prostate cancer masquerading as a primary
      lung tumor. Histologically, the lung tumor displayed eosinophilic crystalloids in
      the malignant glands typical of those previously described in prostatic
      adenocarcinoma. Review of histologic material from 30 additional patients with
      metastatic prostate cancer failed to reveal crystalloids in the metastases. Seven
      patients with histologic material from locally advanced prostatic adenocarcinoma,
      defined as spread to the rectum, bladder, or nonnodal pelvic soft tissue, were
      also reviewed. One of these patients demonstrated crystalloids in the bladder
      extension of locally advanced prostatic adenocarcinoma. Although rare, the
      presence of crystalloids may be used as strong evidence for the prostatic origin
      of an adenocarcinoma of uncertain origin.

PMID- 8135181
TI  - Papillary variant of low-grade mucoepidermoid carcinoma--an unusual bronchial
      neoplasm. A light microscopic, ultrastructural, and immunohistochemical study.
AB  - The authors report an unusual bronchial papillary tumor found in the right lower
      lobe of a 89-year-old woman at the time of postmortem examination. The lesion was
      difficult to classify and did not fit well into any lung neoplasm category. Light
      and electron microscopic features were consistent with a papillary variant of low
      grade mucoepidermoid carcinoma. Differential diagnoses mainly included the
      papillary bronchial mucous gland adenoma and the mixed epithelial-cell-type
      papilloma. Histogenetically, the tumor appeared to originate from the surface
      epithelium. Because the lesion showed features of low malignant potential,
      lobectomy would constitute an appropriate therapy whenever possible.

PMID- 8135182
TI  - Paravaginal female adnexal tumor of probable wolffian origin.
AB  - Female adnexal tumor of wolffian origin (FATPWO) is a lesion that predominantly
      occurs in the broad ligament. Its occurrence in the right paravaginal area is
      rare; only one other case has been reported to occur at this site. The authors
      report a case of paravaginal FATPWO in a 20-year-old woman that recurred twice
      during a 5-year period. The microscopic and ultrastructural features of this
      lesion were identical to other cases of FATPWO reported in the literature. This
      tumor must be recognized, especially at this site, so that it is not confused
      with vaginal adenocarcinoma related to diethylstilbestrol exposure in utero.

PMID- 8135183
TI  - Detection of subgroups of chronic B-cell leukemias by FMC7 monoclonal antibody.
AB  - Monoclonal antibody FMC7 detects subgroups of B-cell leukemias that have arisen
      from cells in late stages of B-cell maturation. FMC7 was studied by flow
      cytometry on cell samples from 192 patients with a diagnosis of chronic
      lymphocytic leukemia (CLL) or lymphoma. The leukemic cells from 16 patients were
      reactive with this antibody. These 16 cases were evaluated for other surface
      markers, morphology of cells, and clinical characteristics. Of the 16 patients,
      14 had cells that strongly expressed surface immunoglobulin (SIg). This is
      atypical of CLL cells, which characteristically show weak expression of SIg.
      Eleven cases had kappa and five had lambda light chain. All patients' cells had
      consistently brighter CD20 expression than that of CD19. Fourteen patients had
      expression of CD5 on their leukemic cells. One patient had more than 55%
      prolymphocytes, meeting the criteria of prolymphocytic leukemia (PLL), two
      patients had CLL in prolymphocytic transformation (CLL/PL), and two other
      patients were classified as having a paraimmunoblastic variant of small
      lymphocytic lymphoma based on a high number of paraimmunoblasts and on the
      histologic features. Another nine patients had immature lymphoid cells distinct
      from prolymphocytes or paraimmunoblasts on morphologic study. The immature cells
      were variable in size, and the nuclear chromatin was less clumped than that of
      prolymphocytes. The histologic diagnoses in four of these cases were consistent
      with mantle cell lymphoma. Splenomegaly was observed in 11 patients (69%), and 11
      patients had advanced Rai 3 or 4 disease. Among 10 patients treated with
      fludarabine, five responded to therapy. Monoclonal antibody FMC7 is useful for
      identifying a group of atypical variants of CLL, PLL, and other B-cell lymphomas
      in leukemic phase that can be easily confused with CLL. Careful attention to the
      cell morphology and histologic features is important for the differential
      diagnosis of FMC7-positive, B-cell lymphoproliferative diseases.

PMID- 8135184
TI  - Molecular genetic, cytogenetic, and immunophenotypic analyses in Castleman's
      disease of the plasma cell type.
AB  - Systemic Castleman's disease shows characteristic morphologic features in the
      lymph node and laboratory findings, but patients with this disease have variable
      clinical courses. The disease may constitute a spectrum of benign to malignant
      diseases. Thus, the clonal nature of the proliferating lymphoid cells was
      determined to obtain further insight into the malignant process of the disease.
      Two cases of systemic Castleman's disease were evaluated immunophenotypically,
      immunogenotypically, and cytogenetically. Both patients had a chronic relapsing
      clinical course. One patient had a clonal rearrangement of the immunoglobulin
      (Ig) lambda chain gene, but no restriction of the light chain expression was
      detected. This patient showed germ-line configurations of the Ig heavy-chain and
      T-cell receptor (TCR) beta chain genes; no detectable abnormal metaphases in the
      lymph node were noted. Another patient had predominance of lambda chain-positive
      plasma cells in the lymph node with a clonal chromosome change, but had germ-line
      Ig and TCR beta chain genes. The authors identified clonal changes in two cases
      of systemic Castleman's disease; one had a clonal immunogenotypic change and the
      other had a clonal cytogenetic change with an Ig light chain deviation. In both
      cases, however, a discordance of immunogenotypic and immunophenotypic changes was
      evident. Thus, the alteration may represent a type of lymphoproliferative
      disorder that lies between benign and malignant diseases.

PMID- 8135185
TI  - Cell kinetic analysis of interleukin-2 receptor-tested chronic lymphocytic
      leukemia using the AgNOR silver stain.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is typically a low-grade neoplasm
      with a diploid DNA index and low proliferative activity. Interleukin-2 receptor
      (IL-2R/CD25) positivity often indicates increased proliferative activity and
      activation in both T and B lymphocytes. The argyrophilic nucleolar organizer
      regions (AgNORs) are loops of DNA identified by a silver staining technique and
      have been correlated with ploidy and proliferative activity. Two distinct AgNOR
      counting methods have been previously shown to correlate with DNA ploidy and
      proliferative activity, respectively: the mean AgNOR count (mAgNOR) correlates
      more with ploidy, and the percentage of nuclei with > or = 5 AgNORs/nucleus
      (pAgNOR) reflects proliferative activity. We studied bone marrow specimens from
      32 patients with B-CLL using both anti-IL-2R on the marrow aspirates and the
      AgNOR silver stain on marrow biopsy specimens, applying both AgNOR counts. All
      tumors were CD5+, CD19+, and CD19/CD20+. Sixteen tumors were IL-2R- (< 20% IL-2+
      B cells), and 16 were IL-2R+ (> or = 20% IL-2R+ B-cells). No significant
      difference in morphology of bone marrow involvement was noted in the two groups.
      A male predominance was noted in the IL-2R+ group of patients (3:1). There was
      also a preponderance of lambda light chain expression in the IL-2R+ tumors
      (11/16) compared with the IL-2R- cases (5/16). Except for two cases, all tumors
      had mAgNOR counts within the diploid range (< 2.4). The 16 IL-2R- tumors had
      pAgNOR in the range of 0% to 7% (mean, 2.31 +/- 2.18 standard deviation), whereas
      the IL-2R+ tumors had pAgNOR ranging from 6% to 15% (mean, 10.20 +/- 2.70
      standard deviation; P < .0001). This finding suggests that IL-2R+ B-CLL might
      represent a subgroup of tumors with higher proliferative activity.

PMID- 8135186
TI  - Bone marrow involvement in large-cell lymphoma. Prognostic implications of
      discordant disease.
AB  - Discordant lymphomas are those in which two different histologic subtypes of non
      Hodgkin's lymphoma are present simultaneously in the same patient at two or more
      separate disease sites. Discordance usually involves a lower grade follicular
      lymphoma in one anatomic site and a higher grade diffuse lesion elsewhere. A
      common type of discordance is seen in patients with a primary diagnosis of
      diffuse large-cell lymphoma (DLCL) who demonstrate bone marrow involvement by a
      lower grade lesion, such as a small cleaved cell or mixed small cleaved and large
      cell lymphoma. This study was undertaken to assess retrospectively the clinical
      implications of such bone marrow involvement, as well as the possible biologic
      mechanisms. Of the 59 DLCL cases studied, 20 (33.9%) showed evidence of bone
      marrow involvement, 14 of which were discordant (70%). The most significant
      findings included the following: Overall treatment responses and survivals in
      discordant patients with predominantly small cleaved cells in the marrow were
      similar to those in patients with no marrow involvement (mean survivals, 47.7 and
      49 months, respectively), and were significantly longer than in patients with
      concordant marrow involvement (mean survival, 13.1 months, P < .05). Patients
      with discordant marrow infiltrates composed of a mixed cell population tended to
      do as poorly as those with concordant involvement. No clear-cut pattern of
      relapse in discordant patients was found, but persistence of small cleaved cells
      in some was reminiscent of lower grade B-cell lesions. Other features associated
      with lower grade lesions included older age, less incidence of central nervous
      system involvement, and lesser extent and proportion of marrow infiltration.
      Finally, in approximately half the cases with discordant involvement, lymphoma
      was present unilaterally, emphasizing the need to perform bilateral biopsies for
      staging.

PMID- 8135187
TI  - Measurement of the intensity of cell surface antigen expression in B-cell chronic
      lymphocytic leukemia.
AB  - Immunophenotyping of peripheral blood lymphocytes from 95 patients with B-cell
      chronic lymphocytic leukemia (B-CLL) was performed to estimate surface membrane
      intensity of the HLA-DR, CD20, and light-chain antigens. Cases were classified as
      having weak, moderate, or strong intensity by a standard slide immunocytochemical
      method, and the fluorescence intensity (FI) was measured by flow cytometry in
      molecules of equivalent soluble fluorescence (MESF). Staining intensity was
      strongest for HLA-DR; with both methods, 94 cases were classified as strong. For
      CD20, 67% were weak, 27% moderate, and 6% strong; the mean MESF values were 31.7,
      66.4, and 177.4 x 10(3), respectively (P < .001). Thirty-nine percent had weak
      surface light-chain staining, 50% moderate, and 11% strong; the mean MESF values
      were 4.9, 7.5, and 16 x 10(3), respectively (P = .005). These results indicate
      that the FI of cell surface antigens can be estimated and quantified by flow
      cytometry. Because of the wide overlap of FI values among the three groups, an
      exact correlation was not found between the two methods of classifying intensity
      of surface antigen expression. The usefulness of these quantitative measurements
      needs further analysis in clinical trials.

PMID- 8135188
TI  - Monoclonal antibodies to Coxiella burnetii for antigenic detection in cell
      cultures and in paraffin-embedded tissues.
AB  - The authors developed monoclonal antibodies to Coxiella burnetti, the agent of Q
      fever. The selected monoclonal antibody, Cox1D8, did not cross-react with other
      bacteria and was used for early detection of C burnetti in shell vial cell
      cultures and for staining C burnetii in paraffin embedded tissues. Formalin or
      Bouin fixation did not alter the reactivity of the antigen with the antibody.
      This monoclonal antibody could be useful in the pathologic diagnosis of Q fever
      hepatitis and endocarditis.

PMID- 8135190
TI  - Misleading hepatitis C serology following administration of intravenous
      immunoglobulin.
AB  - Intravenous immunoglobulin (IVIG) is a blood derivative that is being evaluated
      for the prevention and treatment of numerous disorders. Recent studies have
      suggested beneficial effects from the prophylactic administration of IVIG to very
      low-birth-weight neonates. A disadvantage of such therapy is misleading
      infectious disease serologic assays following administration of IVIG. The authors
      report a recent case in their neonatal intensive care unit of a 24-week
      gestational age girl with a misleading positive hepatitis C serology reaction
      following IVIG administration.

PMID- 8135189
TI  - Disease activity of hepatitis C correlates with single-stage polymerase chain
      reaction detection of hepatitis C virus.
AB  - Hepatitis C virus (HCV) RNA was amplified and detected in the serum of 17 anti
      HCV antibody positive patients using a single-stage (30 cycles) polymerase chain
      reaction (PCR). Specific amplification, targeted to the C-100 protein (anti-HCV)
      region, was confirmed by direct sequencing of the PCR product. Single-stage PCR
      detected the virus in 11 patients. Polymerase chain reaction-positive patients
      demonstrated a significantly higher histologic activity index (10.3 + 1.2
      standard error of mean [SEM] than those testing negative (5.8 + 1.5 SEM, P <
      .05). Nine of 11 PCR-positive patients exhibited a rise in alanine transaminase
      (ALT) values within 1 month of assay, compared with only 1 of 6 PCR-negative
      patients. The correlation between rising ALT levels and PCR positivity was
      significant (P < .01). Direct sequencing revealed mutability in all cases, some
      of which resulted in amino acid substitutions. The authors concluded that HCV
      detection using single-stage PCR correlates with biochemical and histologic
      features of disease activity. Mutability is likely an important feature of HCV
      pathobiology and may significantly affect detection methods.

PMID- 8135191
TI  - Serum levels of erythropoietin and selected other cytokines in patients with
      anemia of chronic disease.
AB  - Serum levels of erythropoietin and five other cytokines potentially operational
      in erythropoiesis were determined in patients with anemia of chronic disease. No
      correlation between erythropoietin levels and severity of anemia was found. A
      spectrum of abnormality was encountered among patients in whom there was less
      than expected erythropoietin response to increased levels of erythropoietin and
      among others in whom the erythropoietin levels were subnormal for their degree of
      anemia. Increased serum levels of interleukin-3, granulocyte colony-stimulating
      factor, and granulocyte-macrophage colony-stimulating factor were encountered in
      limited numbers of patients, especially those with increased erythropoietin
      levels. Deficient erythropoietin production is concluded to be the major cause of
      anemia of chronic disease.

PMID- 8135192
TI  - Thin-layer chromatographic detection of cocaethylene in human urine.
AB  - A thin-layer chromatographic method was developed for the detection of
      cocaethylene and cocaine in human urine. Following a standard solid-phase
      extraction of urine buffered to pH 9.3, the concentrated extract was
      chromatographed in a solvent consisting of hexane:toluene:diethylamine (65:20:5
      mL). Both cocaethylene and cocaine were visualized with iodoplatinate spray.
      Exclusive of the type of extraction used, the detection limit itself was 16 nmol
      (5 micrograms) for either compound. The method was applied to urine samples of 13
      patients who had ingested cocaine with ethanol. Statistically significant
      correlations were noted between the intensity of the urine thin-layer
      chromatographic detection and the measured urine concentrations of cocaethylene
      and cocaine. The plasma and urine concentrations of both drugs also showed
      statistically significant correlations. Incorporation of the proposed procedure
      into commonly used clinical laboratory methodology is described.

PMID- 8135193
TI  - Follow-up testing for ketonuria. Is it necessary?
AB  - The authors examined the utility of confirming positive urinary ketones detected
      by Multistix and the designation of trace ketonuria by Acetest. They also studied
      whether ketonuria should signal a need for microscopic evaluation. They used
      Multistix to test for ketones in 4345 urine samples; 108 samples tested positive
      and were retested using Acetest. The positive predictive value for Multistix was
      98% for samples of small amounts or more of ketonuria. Sensitivity and
      specificity were then assessed on 179 samples tested prospectively by both
      methods. Multistix specificity was high at 96%, but sensitivity decreased from
      87.5% to 63.6% when trace ketonuria was regarded as positive ketonuria. In
      evaluating the usefulness of positive ketonuria to signal a need for microscopic
      examination, the authors found 12% of 78 ketotic, but otherwise negative, samples
      demonstrated positive microscopic findings compared with 15% for 114 chemically
      negative controls. The authors concluded that using Acetest for confirmation is
      necessary only for trace ketonuria by Multistix and that confirmatory testing of
      higher levels of ketonuria incurs increased costs without adding significantly to
      patient care. Using more sensitive Acetest detection levels does not change these
      results. In addition, ketonuria does not appear to signal a need for further
      microscopic evaluation.

PMID- 8135194
TI  - Reduced in vitro displacement of valproic acid from protein binding by salicylate
      in uremic sera compared with normal sera. Role of uremic compounds.
AB  - Limited studies indicate increased free fraction of valproic acid in uremia. One
      study also described displacement of valproic acid from protein binding by
      salicylate in children with epilepsy. The authors studied in vitro interaction of
      valproic acid and salicylate in uremic sera and compared their results with same
      interactions in normal sera. As expected, the concentrations of free valproic
      acid were always significantly higher in uremic sera compared with normal sera.
      When uremic sera were supplemented with both valproic acid and salicylate, a much
      lower displacement of valproic acid by salicylate was observed, compared with the
      effects observed in normal sera. Treatment of uremic sera with charcoal removed
      those uremic compounds, and the concentration of free valproic acid in charcoal
      treated uremic sera were comparable to the concentrations observed in normal
      sera. When uremic compounds were extracted from charcoal with methanol,
      lyophilized, and added to normal serum, an increase in free valproic acid
      concentration in normal serum was observed, indicating that uremic compounds,
      rather than altering albumin structure, are responsible for elevated free
      valproic acid concentration in uremia. However, uremic extract failed to produce
      any further displacement of valproic acid in normal serum in the presence of
      salicylate. The authors concluded that uremic compounds are responsible for
      elevated free valproic acid concentrations, but the displacement of valproic acid
      by salicylate in uremic sera are less remarkable compared with such effect in
      normal sera.

PMID- 8135195
TI  - The impact of autologous blood ordering and blood procurement practices on
      allogeneic blood exposure in elective orthopedic surgery patients.
AB  - The contribution of autologous blood ordering and blood procurement practices on
      subsequent allogeneic blood exposure in elective orthopedic surgery must be
      understood to address the role of aggressive autologous blood procurement in
      blood conservation strategies. The authors examined the relationship between
      autologous blood ordering, blood collection, and subsequent allogeneic blood
      transfusion in orthopedic surgical patients. Of 263 consecutive autologous blood
      donors reviewed, 179 (68%) successfully donated the number of units requested
      (blood ordering cohort). Of these, 17 (9.5%) received allogenic blood. Of 84
      patients unable to donate the units requested, 23 (27%) received allogeneic blood
      (blood procurement cohort). Allogeneic blood exposure in the blood ordering
      cohort occurred at the same prevalence for patients asked to donate < or = 3
      units or > or = 4 units (10[6.8%] of 146 patients and 7[6%] of 116 patients,
      respectively). In contrast, only 3 (2%) of 146 patients asked to donate < or = 3
      units received allogeneic blood in the blood procurement cohort, compared with 20
      (17%) of 116 patients asked to donate > or = 4 units (P < .01). The greatest
      prevalence of allogeneic blood exposure occurred in 13 (35%) of 37 anemic
      (hematocrit level 39% at first donation) patients in the blood procurement cohort
      who could not donate > or = 4 units as requested. The study indicated that both
      blood ordering and blood procurement practices in autologous blood donation
      programs are important factors in blood conservation efforts to minimize
      allogeneic blood exposure.

PMID- 8135196
TI  - A simple method for evaluating prothrombin time in severe liver disease.
AB  - A measurement of prothrombin time by a new, whole blood capillary system was
      evaluated for use in severe liver disease, such as fulminant and chronic hepatic
      failure. The measurement required a single drop of fresh, whole blood and was
      easily performed at bedside. Results were available within 5 minutes after
      collection of the blood samples. Good correlation was observed between
      prothrombin time values determined by the rapid method and those determined with
      the laboratory method (r = .89). The laboratory method was used as a reference.
      The whole blood system may be especially helpful in emergency situations, when
      central laboratory services are not available.

PMID- 8135197
TI  - Is it safe to omit the 37 degrees C reading from pretransfusion red blood cell
      antibody detection testing?
AB  - The routine pretransfusion red blood cell antibody detection test (PADT),
      performed at the authors' institution, consists of a three-phase, saline
      antiglobulin technique (immediate spin, 30-minute incubation at 37 degrees C, IgG
      indirect antihuman globulin test [IAT]), and each phase is examined for hemolysis
      and agglutination. To determine if it would be safe to omit reading the 37
      degrees C phase of the PADT, a 6-year retrospective review of records (February
      1986 to February 1992) was undertaken. Of approximately 280,000 sera tested for
      unexpected red cell alloantibodies, 1480 (.53%) were reactive at only 37 degrees
      C. Of 1480 sera, 1313 contained alloantibodies of no or questionable significance
      (eg, anti-Le(a), anti-Leb, and anti-P1), 71 sera contained antibodies of
      undetermined specificity, and 10 sera were reactive because of rouleaux. Eighty
      six serum samples from 53 different patients contained alloantibodies of
      potential significance (anti-K, anti-E, etc). These 86 sera represented
      approximately 2.2% of all reactive sera that contained potentially significant
      alloantibodies. Although most antibodies (approximately 94%) detected only at 37
      degrees C were of no or questionable significance, the other 6% could have
      increased the risk of missing a potentially significant antibody from
      approximately 1 in every 4700 sera tested to 1 in every 1875 sera tested, had
      they not been detected. The authors suggest that the increased risk of an acute
      or delayed hemolytic transfusion reaction would be too high to justify a
      procedural change. Based on these data, the authors continue to read the 37
      degrees C phase of the PADT for hemolysis and agglutination.

PMID- 8135198
TI  - In vitro analysis of shed blood from patients undergoing total knee replacement
      surgery.
AB  - One method used to obtain autologous blood includes collection of wound drainage
      postoperatively. The decision to wash wound drainage before infusion is left to
      individual institutions. The composition of blood collected from joint spaces has
      not been adequately evaluated. Wound drainage from total knee replacement was
      collected into a cardiotomy reservoir, without anticoagulation, for 4 hours after
      surgery. Coagulation parameters were evaluated on the washed supernatant and
      unwashed supernatant. The most significant findings were the following: 1.
      Modified prothrombin time: washed supernatant and unwashed supernatant were
      substituted for tissue thromboplastin reagent. The unwashed supernatant initiated
      fibrin formation (mean, 108 seconds), whereas the washed supernatant did not
      (mean, > 150 seconds, P = .01). 2. Euglobulin lysis times: Mixtures containing
      50% normal plasma and 50% washed supernatant or unwashed supernatant were used to
      determine plasmin activation (unwashed supernatant + normal plasma = 24 minutes;
      washed supernatant + normal plasma = 106 minutes; P = .03). Lower euglobulin
      lysis times indicates increased plasmin activity. 3. Fibrin degradation products:
      Concentrations were significantly elevated in unwashed supernatant (mean 10,240
      micrograms/mL) versus washed supernatant (mean 5 micrograms/mL, P = .02). Fibrin
      degradation products are inhibitors of fibrin formation and platelets. The
      authors conclude the unwashed supernatant from wound drainage collected after
      total knee replacement contains activated components of the soluble coagulation
      and fibrinolytic systems, and these substances can be significantly reduced with
      washing.

PMID- 8135199
TI  - Autoimmune antibody in a patient with idiopathic thrombocytopenic purpura reacted
      to the platelet low molecular weight glycoproteins and activated platelets.
AB  - The authors characterized antiplatelet membrane antibodies in the sera of
      patients with idiopathic thrombocytopenic purpura (ITP) and cirrhosis of the
      liver. Antibodies were detected in five of the 22 patients with chronic ITP and
      in none of the eight patients with cirrhosis of the liver. The authors report a
      patient with chronic ITP in complete remission. Antibody to platelet
      glycoproteins (GP), with molecular weights of 55 and 49 kDa, was detected in the
      serum. The patient's immunoglobulin G (IgG) alone could cause the aggregation of
      platelet-rich plasma. Anti-GPIIb/IIIa antibody (LJ-CP8) inhibited the aggregation
      of platelet-rich plasma induced by the patient's IgG in a dose-dependent manner.
      The F(ab')2 of the patient's IgG had a synergetic effect on the aggregation of
      PRP induced by adenosine 5-diphosphate. This demonstrates that in ITP, the
      binding of IgG via its fragment of antigen binding site portion may activate
      platelets.

PMID- 8135200
TI  - Management of mammographically detected breast lesions.

PMID- 8135201
TI  - Handling of fine-needle aspirate material to prevent drying artifacts.

PMID- 8135202
TI  - Uniform examination protocols.

PMID- 8135203
TI  - Failure of the INR.

PMID- 8135204
TI  - The SPEED appliance: a 14-year update on this unique self-ligating orthodontic
      mechanism.
AB  - Since its inception in 1975, the SPEED appliance has undergone many significant
      design improvements. This article is intended to describe the various integral
      components of the SPEED appliance and review the function of each.

PMID- 8135205
TI  - Abnormal function of the temporomandibular joints and musculature. Part 3.

PMID- 8135206
TI  - The validity of the prediction of Soft Tissue profile changes after LeFort I
      osteotomy using the dentofacial planner (computer software).
AB  - The purpose of this study was to examine the validity of the prediction of soft
      tissue changes after LeFort I osteotomy with the DentoFacial Planner (DFP)
      (computer software). The preoperative and postoperative lateral cephalograms of
      21 white adult orthodontic patients (10 males and 11 females) who underwent only
      LeFort I osteotomy as part of their overall treatment were digitized. A
      coordinate system of X and Y axes were used to assess the amount and direction of
      movement of the maxilla. The SN + 7 degrees was the X axis, and a perpendicular
      to this plane from nasion was the Y axis. The sample was divided into two groups
      depending on the amount of forward movement of the maxilla. More than 2 mm of
      anterior placement of the maxilla comprised the advancement group (13 patients)
      and less than 2 mm comprised the impaction group (8 patients). The selection
      criteria for the sample were (1) before and after cephalograms taken with lips in
      repose and in centric occlusion; (2) all preoperative records taken almost
      immediately before surgery; (3) postoperative records taken at least 6 months
      after surgery and checked by regional superimposition of the preoperative and
      postoperative lateral cephalograms onto the maxilla and the mandible. No tooth
      movement occurred between the time the records were taken. The following soft
      tissue landmarks were examined: pronasale, subnasale, stomion superior, middle
      upper lip, stomion inferior, middle lower lip, labrale inferior, labiomental
      fold, and pogonion. The results indicate that for some of these landmarks the
      amount and direction of soft tissue changes differed between the DFP prediction
      and the actual surgical changes by LeFort I osteotomy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8135207
TI  - Comments on pediatric internal derangements.

PMID- 8135208
TI  - Profile enhancement and cephalometric landmark identification.
AB  - The reproducibility of two soft tissue landmarks (SN, V) and two anterior bony
      landmarks (A, ANS) was determined by three observers for three cephalometric
      techniques. The three techniques were aimed at soft tissue profile enhancement
      either by standard exposure control (technique 1), a hand-held metal shield
      covering the profile (technique 2), or a brass wedge in the collimator (technique
      3). For each technique, the sample was restricted to 20 subjects with a skeletal
      convexity greater than +4 mm. The four landmarks were identified three times with
      7-day intervals between readings. The figure-of-merit (or mean radius) method was
      used to assess the probability of "hitting" a target (landmark) area. The mean
      radius from the sample mean point of impact (MPI) ranged from 0.585 mm to 1.758
      mm. For a specific landmark, the difference was never greater than 0.5 mm when
      grouped by observer and technique. No technique excelled in overall consistency
      for the identification of anterior bony and soft tissue landmarks. Techniques 1
      and 3 produced the most consistent identification of points ANS and SN, but with
      no significant difference between the two techniques. Interacting factors
      prevented any recommendation regarding a preferential technique for the
      identification of points A and V. There is statistically no reason to recommend
      the use of a handheld, metal profile shield for more consistent landmark
      identification.

PMID- 8135209
TI  - Anatomic basis for disk displacement in temporomandibular joint (TMJ)
      dysfunction.
AB  - This study was designed to investigate the site of lateral pterygoid muscle
      insertion into the temporomandibular joint (TMJ) disk, and the relationship
      between that attachment and the disk displacement. One hundred and ten TM joints
      from 78 cadavers were collected and sectioned in the sagittal plane. Sixty-two
      unilateral specimens were available and 16 additional specimens were selected
      randomly from the remaining cadavers in which both condyles were available. Thus
      statistical comparisons were not confounded by autocorrelation and were based on
      78 independent specimens. The sites of muscle attachment in relation to the disk
      were identified histologically. Of the 78 joints 49 had anterior disk
      displacement. Of the 42 cases with insertion directly into the disk, 30 had
      anterior disk displacement. In contrast, only 19 of the 36 disks without direct
      muscle insertion were displaced. This finding indicated a statistically
      significant relationship between functional muscle attachment and disk
      displacement (chi 2 = 9.28, df = 1, p = 0.006). However, the superior head of the
      lateral pterygoid muscle (SLP) may not be the precipitating factor for anterior
      disk displacement even though it does coordinate disk movement on closure. Since
      other factors (e.g., trauma) can result in disk displacement, the SLP can
      maintain disk displacement only when it inserts directly into the disk. In cases
      of normal disk arrangement and condylar attachment, the muscle may not play a
      clinically significant role in disk displacement because disk attachment at the
      medial and lateral poles of the condyle allows the disk to move freely with the
      condyle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135210
TI  - Comments on pediatric internal derangements.

PMID- 8135211
TI  - A modification of the pressure-flow technique for measuring breathing of cold air
      and its effect on nasal cross-sectional area.
AB  - The purpose of this article was to develop a method based on the pressure-flow
      technique for measuring cold air breathing and to observe the immediate reactions
      of breathing function to cold air inhalation in 40 subjectively healthy adults.
      The pressure-flow technique was used to measure airflow rate and oral/nasal
      pressure and to calculate the smallest cross-sectional area of the nasal airway.
      The equipment was modified to allow measurements both at room temperature and
      with cooled air by connecting the nasal mask to a freezer with a two-valve
      cylinder and tubing. Nasal cross-sectional area showed a significant decrease
      from 42.3 mm2 at room temperature to 37.6 mm2 with cooled air. Correspondingly,
      the airflow rate changed from 411 ml/s to 369 ml/s, whereas the differential
      pressure remained about the same, 1.2 and 1.3 cm H2O, respectively. The
      interindividual variation was fairly large. The results suggest that the
      breathing of cold air seems to cause changes in nasal cross-sectional area and
      airflow rate. In general, the cross-sectional area diminishes, the change being
      quantitatively more pronounced in subjects with an initially large area.

PMID- 8135212
TI  - Growth changes in the craniofacial complex of the rat after prolonged papain
      administration.
AB  - The purpose of the study was to evaluate by radiographic and biometric means the
      effects of prolonged papain administration on growth of the craniofacial complex,
      to gain further insight into the importance of cranial cartilage for skull
      enlargement during rapid skeletal growth (25 to 70 days of age). Fifty 21-day-old
      male Lewis strain rats were divided randomly into three groups. Group 1 (n = 20)
      received 45 daily injections intraperitoneally of a 2% solution of crude papain
      in normal saline from 25 to 70 days of age. Group 2 (n = 20) were given 30 daily
      injections at the same dose level from 40 to 70 days of age, and group 3 (n = 10)
      served as untreated controls. Animals were weighted daily until 70 days of age
      and then every other day until killed at day 120. Submental-vertex and lateral
      skull radiographs were obtained at 25, 40, 53, 70, 90, and 120 days of age with
      standardized skull positioning and radiographic settings. Cephalometric
      measurements of 22 linear dimensions were made in each of 360 cephalograms, and
      the data analyzed statistically with Student's t test. Growth velocity curves
      were evaluated for evidence of catch-up growth. Body-weight gain by papain
      treated groups was less than for controls (p < 0.001). Skull and nasal lengths,
      middle cranial base length, and sphenoidal length were significantly shorter (p <
      0.001). Neurocranial length was also shortened, whereas neurocranial height and
      supraoccipital height increased. Reduction of skull dimensions was generally more
      pronounced in the earlier injected group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135214
TI  - Comments on pediatric internal derangements.

PMID- 8135213
TI  - Risk factors associated with temporomandibular joint sounds in children 6 to 12
      years of age.
AB  - The relationship between temporomandibular joint (TMJ) sounds and a person's
      dental and skeletal characteristics is poorly understood. In this study, data
      were obtained from 3428 grade schoolchildren (mean age = 9.0 years, SD = 0.8,
      range 6 to 12 years), without a history of orthodontic treatment. Each child had
      been examined independently by one of six orthodontists to assess: TMJ sounds
      (none, click, crepitus), gender, age, race (white/black), skeletal relationships
      (convexity, maxillary, and mandibular positions), malocclusion (molar class,
      overjet, overbite, anterior crowding, posterior crossbite), maximum opening, chin
      trauma (none, cut, scar), and history of lower facial trauma. Temporomandibular
      joint sounds were present in 344 children (10.0% of the sample); 276 (8.1%) had
      an isolated unilateral sound, 254 (7.4%) had unilateral clicking, 50 (1.5%) had
      bilateral clicking, 22 (0.6%) had unilateral crepitus, and 11 (0.3%) had
      bilateral crepitus. Univariate analyses compared children with and without sounds
      for each variable; logistic regression analyses examined the relationship between
      groups of variables and TMJ sounds. The prevalence of TMJ sounds was associated
      with examiner (chi 2 = 23.4, df = 5, p < 0.001); increased prevalence of TMJ
      sounds occurred in children with maxillary anterior crowding (t = 2.8, p <
      0.006), mandibular anterior crowding (t = 3.0, p < 0.002), and increased maximum
      opening (t = 4.7, p < 0.001). In contrast to other reports on children, the
      prevalence of joint sounds was not associated with age, race, gender, or molar
      class.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135215
TI  - Maturational evaluation of ossification of the midpalatal suture.

PMID- 8135216
TI  - The effect of titanium tetrafluoride (TiF4) application around orthodontic
      brackets.
AB  - In the present in vivo study, the cariostatic potential of a titanium
      tetrafluoride (TiF4) solution applied topically around orthodontic brackets was
      investigated with quantitative microradiography. Also characteristics of the TiF4
      treated enamel surface were examined with scanning electron microscopy (SEM). Ten
      pairs of premolars to be extracted for orthodontic treatment were used in the
      first part of this study. Brackets were bonded on all teeth with an orthodontic
      adhesive, and 10 randomly selected premolars served as controls, whereas a
      similar number were treated with 1% TiF4 around brackets for 60 seconds. After 4
      weeks with no topical fluoride supplementation, all teeth were extracted and
      stored for analysis. Results indicated the 1% TIF4 solution reduced lesion depths
      and total mineral loss, at the bracket periphery, significantly during the 4-week
      period. The presence of a surface coating was demonstrated by SEM micrographs. It
      was concluded that TiF4 may provide a high level performance as a prophylactic
      agent for orthodontic purposes.

PMID- 8135217
TI  - Improvement of masticatory function after orthodontic treatment. Two case
      reports.
AB  - In patients with temporomandibular joints dysfunction (TMD), the masticatory
      function is often altered in that: (1) the intercuspal position (ICP) is less
      frequently achieved; (2) the mean vertical displacement from ICP at the end of
      opening is above normal; and (3) the isometric muscle contraction pattern during
      closure tends to be suppressed. We describe two cases of growing patients with
      severe malocclusion, who showed the same functional alterations as patients with
      TMJ before treatment, and normalization of the masticatory function after
      orthodontics.

PMID- 8135219
TI  - Creating multiple reports using primary (form) files which merge with multiple
      secondary (data) files.

PMID- 8135218
TI  - Comments on pediatric internal derangements.

PMID- 8135220
TI  - Restrictive covenants.

PMID- 8135221
TI  - Comments on pediatric internal derangements.

PMID- 8135222
TI  - Comments on pediatric internal derangements.

PMID- 8135223
TI  - Comments on pediatric internal derangements.

PMID- 8135224
TI  - Comments on mandibular condyle position.

PMID- 8135226
TI  - How to motivate pharmacy students and residents.

PMID- 8135227
TI  - Indoor air is nearly cleanroom quality.

PMID- 8135225
TI  - Comments on pediatric internal derangements.

PMID- 8135228
TI  - Establishment of clinical pharmacy services in an ambulatory-care clinic in a
      housing project.

PMID- 8135229
TI  - Patient anonymity precludes pharmaceutical care.

PMID- 8135230
TI  - Studies on long-term, not short-term, effects of antineoplastic drug handling are
      needed.

PMID- 8135231
TI  - If the public only knew.

PMID- 8135232
TI  - Harvey A. K. Whitney Lecture. Shifting pharmacy's paradigm.
AB  - Changes occurring in the pharmacy profession and their effects on the paradigm
      for pharmacy practice are discussed. The paradigm of pharmacy, the pattern or
      model of pharmacy's structure, services, daily activities, and organization, is
      shifting, and if pharmacists do not shift with it, they will be left behind.
      Advances in technological capabilities often result in automation and
      centralization of services. Improvements in drug therapy have caused shifts in
      the performance of clinical functions. Philosophical changes about the way health
      care should be delivered have produced the concepts of pharmaceutical care,
      patient-focused care, and continuous quality improvement of care. Teams of
      caregivers whose primary concern is the patient have replaced caregiving based on
      technology, discipline, or employee needs. Pharmacists have focused on the
      patient as their primary customer instead of the nurse or practitioner, and they
      anticipate the patient's needs in a structured and documented fashion. The
      principles of continuous quality improvement have been applied to every aspect of
      providing pharmaceutical care. If pharmacists are to adjust to the shift in the
      pharmacy paradigm, they must recognize their strength as a group, make proper
      recommendations about pharmaceutical use, move horizontally to grow as
      professionals, consider themselves clinicians, be active in the making of
      pharmaceutical care decisions, and believe in themselves.

PMID- 8135233
TI  - Effect of pharmacists on health care outcomes in hospitalized patients.
AB  - The cost-effectiveness of pharmacists and their effect on inpatient health care
      outcomes were evaluated. For one year, data were collected on all patients
      receiving care from general medicine and general surgery teams at Walter Reed
      Army Medical Center, Washington, D.C. Two of five medicine teams and one of three
      surgery teams included a pharmacist. Teams that included a pharmacist were
      compared with teams that did not, in terms of patients' length of stay (LOS),
      mortality, and drug cost per admission. Data were compared for 3081 patients and
      collected for another 557 who were not included in the comparative study design.
      Health care teams that included a pharmacist had a shorter log LOS and lower log
      drug cost per admission but no difference in mortality. The average cost savings
      for teams that included a pharmacist was $377 per inpatient admission, and the
      benefit-to-cost ratio was 6.03:1. The inclusion of pharmacists on health care
      teams was cost-effective and provided a favorable benefit-to-cost ratio.

PMID- 8135234
TI  - Care plan for documenting pharmacist activities.
AB  - At a 393-bed hospital, a pharmaceutical care plan was developed and tested in a
      surgical intensive care unit (SICU). The trial care plan was developed and
      implemented with the following objectives: to integrate clinical and distributive
      elements of patient information in a care plan; to add new monitoring and
      intervention parameters to the pharmacy profile; and to assess and refine the
      care plan for implementation in other areas of the institution. One pharmacist
      performed and documented care for 10 patients in the SICU. The pharmacist planned
      appropriate drug administration schedules, noted appropriate indications for each
      medication ordered, established appropriate outcomes, monitored for drug-drug or
      drug-food interactions and allergies, recorded interventions and averted adverse
      drug reactions, and recorded the amount of time required for care according to
      disease state. Pharmacist involvement with medication administration and
      monitoring seemed to prevent many adverse effects and drug interactions. Because
      of the diversity of the patient population, there was substantial variation in
      the time spent on care. A trial pharmaceutical care plan in a surgical intensive
      care unit was useful for documenting pharmacists' productivity and effectiveness.

PMID- 8135235
TI  - Capability of hospital computer systems in performing drug-use evaluations and
      adverse drug event monitoring.
AB  - A survey to determine the extent of computerization in key areas of hospitals,
      the information being collected in the databases, and the capabilities of the
      computer systems for performing adverse drug event monitoring and drug-use
      evaluations was conducted. The questionnaire was distributed to clinical
      pharmacists in the 500 hospitals composing the Drug Surveillance Network. In the
      majority of the 166 responding hospitals (> 85%), the pharmacy department,
      clinical chemistry and hematology laboratories, patient admissions, and
      microbiology laboratory were computerized for data acquisition and management.
      The medical records and purchasing departments were computerized in a smaller
      proportion of hospitals (75% and 74%, respectively). In the majority of hospitals
      with a computerized pharmacy department (> 78%), there was ready access to
      computer databases in other departments, but simultaneous querying of multiple
      databases was possible in only 30%. Patients could be identified according to
      diagnosis in 82% of the hospitals and according to medication received in 83%.
      More than 85% of responding hospitals had implemented spontaneous reporting
      systems for the identification of adverse drug events. Computers are widely used
      in hospitals participating in the Drug Surveillance Network, but a substantial
      effort is necessary to make these resources more useful and to standardize
      processes so that data may be pooled across institutions to deal with important
      public health concerns.

PMID- 8135236
TI  - Pharmaceutical services at a medical site after Hurricane Andrew.
AB  - The experiences of a group of volunteer clinical pharmacists who provided
      pharmacy services as part of a disaster relief effort following a hurricane are
      reported. Hurricane Andrew left many people in southern Florida without shelter
      and other basic necessities, including health care services. A group of seven
      pharmacists volunteered to provide services at a temporary medical site set up in
      a community center. The pharmacy stock consisted of donated drugs. The
      pharmacists dispensed medications directly to patients and worked closely with
      other volunteer medical personnel to make sure proper medications were used.
      Because the pharmacy stock was limited, physicians relied upon the pharmacists
      for information about therapeutic interchanges, dosage conversions, and new
      medications. Prescriptions were often ordered and dispensed with only oral
      instructions. The pharmacists also provided patient counseling, although problems
      caused by inexperience with certain types of patients, a language barrier, and
      substandard living conditions after the hurricane made counseling more difficult.
      The contributions of seven pharmacists who provided services at an emergency
      medical site after Hurricane Andrew were well received by other health care
      personnel and by the community.

PMID- 8135237
TI  - Effects of injection site and flow rate on the distribution of injected solutions
      in an extracorporeal membrane oxygenation circuit.
AB  - The effects of injection site and flow rates on drug distribution within an
      extracorporeal membrane oxygenation (ECMO) circuit were studied. Two commercially
      available reservoirs (30 mL and 50 mL) were connected to a closed ECMO circuit
      that did not include the membrane oxygenator and heater. The circuit was filled
      with 150-170 mL of a 9.5% dextran solution in deionized, distilled water with a
      viscosity approximating that of blood. Flow rates of the circulating solution
      were set at 75 mL/min and 375 mL/min. Bordeaux red dye was injected into an ECMO
      circuit at prereservoir, postreservoir, and intrareservoir sites, and samples
      were obtained from these sites for analysis. Gentamicin was also injected at the
      prereservoir site, with samples obtained from the reservoir, reservoir tubing,
      and the prereservoir and postreservoir sites. Postreservoir dye injections
      resulted in complete mixing at any flow rate. Prereservoir injections at flow
      rates less than 250 mL/min resulted in incomplete mixing of dye, whereas
      intrareservoir injections resulted in incomplete mixing at any flow rate.
      Gentamicin injection was also affected by flow rate, resulting in higher
      concentrations within the reservoir and reservoir tubing. In patients on ECMO,
      drug distribution may be substantially altered if drugs are given as a bolus at
      prereservoir or intrareservoir sites. Efforts should be made to select injection
      sites that will provide safe and therapeutic drug delivery while minimizing the
      effects of the ECMO circuit on drug distribution.

PMID- 8135238
TI  - Stability of flumazenil with selected drugs in 5% dextrose injection.
AB  - The compatibility and stability of flumazenil mixed with aminophylline,
      dobutamine hydrochloride, dopamine hydrochloride, cimetidine hydrochloride,
      famotidine, ranitidine hydrochloride, heparin sodium, lidocaine hydrochloride, or
      procainamide hydrochloride were studied. Flumazenil (1.0 mg) was mixed with each
      of the other drugs in polyvinyl chloride minibags containing 50 mL of 5% dextrose
      injection to achieve concentrations commonly used when the drugs are administered
      by continuous i.v. infusion. All admixtures were analyzed for color change, pH,
      and particulate matter. Flumazenil concentrations were measured by a stability
      indicating high-performance liquid chromatographic assay at baseline and 2, 4, 8,
      12, and 24 hours after mixing. No detectable changes in color, pH, or particulate
      matter were observed. In the presence of each drug except dopamine hydrochloride,
      at least 95% of initial flumazenil concentration was present 24 hours after
      mixing. Flumazenil in the presence of dopamine hydrochloride was stable for 12
      hours. Flumazenil was visually compatible and chemically stable when admixed with
      5% dextrose injection and selected drugs.

PMID- 8135239
TI  - National adverse drug event reporting.

PMID- 8135240
TI  - Use of medical record codes to identify adverse drug reactions.

PMID- 8135241
TI  - Patient-teaching service at a university medical center.

PMID- 8135243
TI  - Membrane filtration of pharmaceutical solutions.
AB  - The principles and uses of membrane filtration in the preparation of
      pharmaceutical solutions are discussed. The preparation of pharmaceutical
      solutions often requires their passage through a thin polymeric membrane
      containing many tiny pores. The purpose is to remove viable and nonviable
      particles in order to clarify or sterilize the solution. Particles may be
      retained by sieving, entrapment, or electrostatic attraction. The largest pore
      size that will yield a sterile filtrate is 0.2 microns. Membrane filters are
      either hydrophobic or hydrophilic. The rate of flow through a filter is affected
      by the resistance of the filter, the viscosity of the solution, and pressure.
      Filters are commonly composed of mixed esters of cellulose, polysulfone,
      polyvinylidene difluoride, nylon 66, polycarbonate, or polytetrafluoroethylene.
      In selecting a membrane filter, a pharmacist must consider pore size,
      compatibility, fluid volume, particulate load, and the filter holder. Various
      tests are available to evaluate the integrity of filters. Filters are useful in
      testing end products for sterility. The use of an in-line filter during the
      administration of large-volume injectable solutions can prevent the introduction
      of particles, air, and microorganisms into the patient. Therapies in which a 0.2
      micron filter may be contraindicated include lipid emulsions, low-dose infusions,
      low-volume infusions, drugs for which the pharmacologic properties are altered by
      the membrane filter, and drugs that adhere to the membrane. Pharmacists need an
      in-depth understanding of the principles of filtration, the characteristics of
      filters, and their use in the filtration of pharmaceutical solutions.

PMID- 8135242
TI  - Stability of ondansetron hydrochloride stored in a disposable, elastomeric
      infusion device at 4 degrees C.

PMID- 8135244
TI  - Right of a defendant to refuse antipsychotic medication during a criminal trial.

PMID- 8135245
TI  - ASHP guidelines on the pharmacist's role in home care. American Society of
      Hospital Pharmacists.

PMID- 8135246
TI  - Ethical issues raised by the Human Genome Project.

PMID- 8135247
TI  - Criteria for use of propofol in critically ill adults. American Society of
      Hospital Pharmacists.

PMID- 8135248
TI  - Criteria for use of propofol for anesthesia in adults. American Society of
      Hospital Pharmacists.

PMID- 8135249
TI  - Erythema multiforme and angioedema with indapamide and sertraline.

PMID- 8135250
TI  - Controlling high-cost drug use.

PMID- 8135251
TI  - Re-evaluating reporting rates for adverse drug reactions.

PMID- 8135252
TI  - Cultural diversity and Kingian nonviolence.

PMID- 8135253
TI  - More than just a mouth swab.

PMID- 8135254
TI  - One syringe is better than two.

PMID- 8135255
TI  - Analyze costs in addition to ethics.

PMID- 8135256
TI  - Intensive insulin therapy can delay long-term complications of diabetes, study
      shows.

PMID- 8135257
TI  - Rimantadine approved for treatment, prophylaxis of influenza A.

PMID- 8135258
TI  - Pediatrics academy updates guidelines on ribavirin use. American Academy of
      Pediatrics.

PMID- 8135259
TI  - Reducing demand through preventive care.

PMID- 8135260
TI  - Amlodipine: a new calcium antagonist.
AB  - The chemistry, pharmacology, pharmacokinetics, efficacy, and adverse effects of
      amlodipine are reviewed. Amlodipine belongs to the dihydropyridine subclass of
      calcium antagonists. Amlodipine is a potent peripheral and coronary vasodilator
      with high selectivity for vascular smooth muscle and minimal effect on myocardial
      contractility or cardiac conduction. Absorption after oral administration is
      slow, and the duration of action is long, with a half-life of 36-45 hours.
      Amlodipine has FDA-approved labeling for use in the treatment of hypertension,
      chronic stable angina, and vasospastic angina. The agent is also indicated for
      use in hypertensive or anginal patients who also have congestive heart failure
      due to systolic dysfunction (New York Heart Association classes II and III).
      Clinical trials suggest that effective 24-hour control of hypertension and angina
      is provided by once-daily administration of amlodipine 5-10 mg alone or in
      combination with other drugs. No clinically important drug interactions have been
      observed to date. Amlodipine has not shown any unfavorable effects on serum
      glucose or lipid levels. The most common adverse effect is peripheral edema.
      Amlodipine is effective and well tolerated when given alone or in combination
      with other drugs for the treatment of hypertension and angina. Amlodipine may
      offer advantages over verapamil, diltiazem, and nifedipine in patients with
      hypertension or angina with associated congestive heart failure due to systolic
      dysfunction.

PMID- 8135261
TI  - Pharmacists' attitudes toward physician-assisted suicide.
AB  - Pharmacists' attitudes toward physician-assisted suicide were measured. Surveys
      were mailed to a national random sample of 1050 licensed pharmacists. Part 1 of
      the survey collected information about the respondents and their education and
      practice setting. Part 2 asked them to indicate "yes," "no," or "unsure" in
      response to questions about physician-assisted suicide and to rank the intensity
      of their religious conviction. Part 3 solicited respondents' opinions about
      physician-assisted suicide. Respondents returned 534 completed questionnaires.
      Most of the respondents (72.6%) believed that patients are sometimes justified in
      wanting to end their own lives but only 48.6% believed that physicians should
      actively help their patients die. Of those who believed that physician-assisted
      suicide may be appropriate in some situations, 70.9% considered it to be an
      appropriate use of prescription drugs. Among respondents who believed that
      physician-assisted suicide may sometimes be appropriate, 66.6% believed it is
      inappropriate for a physician to involve a pharmacist without the pharmacist's
      knowledge and consent. However, only 53.8% indicated that they would want to know
      if a prescription they dispensed were going to be used in a physician-assisted
      suicide, and only 34.3% indicated that they would ever knowingly participate in
      one. Younger pharmacists and those with a high degree of religious conviction
      were significantly more negative toward physician-assisted suicide. Comments in
      part 3 indicated that personal experiences also influenced pharmacists' attitudes
      toward physician-assisted suicide. Pharmacists' opinions about physician-assisted
      suicide vary considerably and seem to be associated with factors such as personal
      experiences, religious conviction, and age.

PMID- 8135262
TI  - Medication-related stressors among family caregivers.
AB  - The contribution of medications to stress among family caregivers and the need of
      caregivers for pharmaceutical care services were studied. Persons in northern
      Florida who were caring for a family member at home who was at least 55 years of
      age and routinely took at least one medication were asked if they would consent
      to an interview. The interview was designed to elicit information about the
      characteristics of the caregiver and care recipient, stressors stemming directly
      from the medications (such as adverse effects) and arising from problems in
      managing the drug regimen (such as compliance), the mediators of medication
      related stress (such as services received from the pharmacist), and the outcomes
      of stress (such as the caregiver's satisfaction with services). A total of 31
      caregivers agreed to be interviewed. The mean +/- S.D. ages of caregivers and
      recipients were 63 +/- 13 and 80 +/- 10 years, respectively. Medication-related
      tasks accounted for only 7.7% of the total caregiving time. However, medications
      contributed substantially to caregivers' stress, with 10 caregivers (32%)
      reporting problems directly related to medications and 6 (19%) and 16 (52%)
      reporting problems in managing the drug regimen currently or within the past
      year, respectively. Twenty-two (71%) used the same pharmacy regularly, and 18
      (58%) saw the same pharmacist regularly. Twenty-five caregivers talked with
      others about medication concerns. Of these, 18 (72%) discussed their charge's
      drug therapy with a physician but only 10 (40%) with a pharmacist.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8135264
TI  - Childhood immunizations: studies shed light on risk, parents' behavior.

PMID- 8135263
TI  - Accuracy of penicillin allergy reporting.
AB  - The consistency of penicillin allergy documentation in the patient chart,
      pharmacy profile, and medication administration record was assessed, along with
      the correctness of the self-reported patient history of penicillin allergy. One
      hundred fifty adult inpatients with a reported penicillin allergy were
      interviewed about their allergy. Questions included length of time since the
      allergic reaction, symptoms of the reaction, and whether rechallenge was ever
      attempted. Patients were classified into categories of (1) more severe allergy,
      (2) less severe allergy, or (3) intolerance on the basis of results of the
      interview. The patient pharmacy profile, chart, and medication administration
      record were reviewed to determine whether the allergy label was present. Patients
      who received antimicrobials during their hospitalization were evaluated. Of 117
      patients, 82.9% were classified as allergic and 17.1% as intolerant. The allergy
      was documented in 98.7% of patient charts and 96.7% of medication administration
      records. The symptoms of the allergic reaction were described in the chart for
      only 34% of patients. Agents substituted for penicillin were potentially more
      toxic in 70.4% of cases, equally effective in all cases, and more costly in 55.5%
      of cases. Most, but not all, patients labeled as penicillin allergic had a
      history consistent with an allergy to the drug. Pharmacists can help ensure
      accurate allergy documentation by evaluating patients and educating both patients
      and health care professionals.

PMID- 8135265
TI  - Multidisciplinary committee on the abuse of prescription medications.
AB  - A program for (1) coordinating the care of patients suspected of abusing
      prescription medications and (2) providing data on the long-term outcomes of
      these interventions is described. A substance abuse committee composed of
      physicians, psychologists, pharmacists, and administrators was established to
      review individual cases of suspected misuse or abuse of medications at a large
      Department of Veterans Affairs medical center. After reviewing each case, the
      committee recommended specific actions, such as requesting that the identified
      medication be restricted from the patient or that the patient receive counseling
      or treatment for substance abuse. To evaluate the program's effectiveness, the
      records of the 161 cases referred to the committee between 1981 and 1992 were
      reviewed. The patient's outcome one year after committee intervention could be
      determined in 105 cases. Of those, 70 revealed either no evidence of continuing
      prescription drug abuse or reduced use of the targeted medication in the medical
      center. Eighteen other patients were no longer receiving care at the institution.
      A multidisciplinary substance abuse committee helped identify and treat patients
      suspected of abusing prescription drugs.

PMID- 8135266
TI  - Stability of foscarnet sodium in 0.9% sodium chloride injection.
AB  - The stability of foscarnet sodium in 0.9% sodium chloride injection was studied.
      Foscarnet sodium 24 mg/mL was added to polyvinyl chloride i.v. bags containing
      0.9% sodium chloride injection to give a theoretical foscarnet sodium
      concentration of 12 mg/mL. Ten bags of solution were stored at 25 degrees C in
      normal laboratory light, 10 bags were stored at 25 degrees C in the dark, and 10
      bags were stored at 5 degrees C in the dark. Samples were analyzed for foscarnet
      concentration by high-performance liquid chromatography on days 0, 3, 8, 10, 15,
      and 30. The solutions were visually inspected for particulates, and pH was
      measured. Foscarnet sodium was stable in all the solutions for up to 30 days
      under all the storage conditions; mean foscarnet concentrations did not decline
      below 99% of initial values. No particulates appeared, and there were no
      important changes in pH. Foscarnet sodium 12 mg/mL in 0.9% sodium chloride
      injection was stable for up to 30 days when stored at 25 degrees C and exposed to
      light, 25 degrees C and protected from light, or 5 degrees C and protected from
      light.

PMID- 8135267
TI  - Pharmacist participation on a multidisciplinary rehabilitation team.

PMID- 8135268
TI  - Stability of ceftriaxone sodium and aminophylline or theophylline in intravenous
      admixtures.

PMID- 8135269
TI  - Stability of captopril in three liquid dosage forms.

PMID- 8135270
TI  - Single-dose intravenous immune globulin for treatment of Guillain-Barre syndrome.

PMID- 8135271
TI  - Smith-Fineman-Myers syndrome: report on a large family.
AB  - Smith-Fineman-Myers syndrome is considered an X-linked mental retardation (XLMR)
      syndrome. Three families have been reported to date. However, none presented a
      typical pattern of X-linked inheritance. Here we reported on 5 males with Smith
      Fineman-Myers syndrome with similar phenotypic expression as in those cases
      reported previously; they were distributed in 4 sibships of one large maternal
      kindred. This finding adds strong support to the hypothesis of the Smith-Fineman
      Myers syndrome being a rare XLMR syndrome.

PMID- 8135272
TI  - Monosomy 11q: report of two familial cases and review of the literature.
AB  - We present four children from two families with the typical 11q- phenotype
      resulting from an unbalanced segregation of a parental translocation. In the
      first family, the father had a 46,XY,t(5;11)(q24;q23.3) constitution. The father
      of the three other children had a 46,XY,t(11;17)(q23;p13) translocation. Despite
      associated partial deletion, three of the children had a typical 11q- phenotype.
      The fourth one, whose pregnancy was terminated in the second trimester, had a
      hypoplastic left heart but no other considered gross anomalies. A review of 36
      previous cases, including 5 due to translocations (4 familial rearrangements, and
      1 of unknown origin) is given with emphasis on the relationships between break
      points and phenotype. Undescribed manifestations in our patients include agenesis
      of corpus callosum adactyly and malrotation of the gut.

PMID- 8135273
TI  - Polysplenia syndrome and congenital short pancreas.
AB  - We present a report of a stillborn female of mixed ancestry with congenitally
      short pancreas, polysplenia, congenital heart defect, normal bronchial branch
      pattern, and interruption of the inferior vena cava to add to the growing numbers
      (15) of this malformation complex in the literature. Additional manifestations
      were congenital hydrocephalus and absence of intestinal malrotation. A recent
      poster presentation at the Second International Workshop on Fetal Genetic
      Pathology in Montana by Drut et al. underlined the importance of reporting these
      cases and of the pathological examination required ["Abnormal Spleen Lobulation
      and Short Pancreas," in Blastogenesis-Normal and Abnormal. New York: Wiley-Liss,
      Inc. for the National Foundation-March of Dimes, 1993].

PMID- 8135274
TI  - Familial Pallister-Hall syndrome: case report and hormonal evaluation.
AB  - Pallister-Hall syndrome is a usually lethal dysplasia/malformation syndrome
      characterized by hypothalamic hamartoblastoma, hypopituitarism, postaxial
      polydactyly, craniofacial malformations, imperforate anus, and other
      malformations. We report a familial case in a male infant and his female sib
      fetus, suggesting autosomal recessive inheritance, or germinal mosaicism for an
      autosomal dominant mutation, or a segregating submicroscopic chromosome
      abnormality. Detailed endocrine evaluation on the surviving infant revealed
      documented pituitary function, pituitary deficit, and hypothalamic deficiency. We
      suggest that hypothalamic dysfunction contributes to the hypopituitarism seen in
      Pallister-Hall syndrome.

PMID- 8135275
TI  - Cardio-facio-cutaneous (CFC) syndrome in a child carrying an inherited inversion
      of chromosome 7.
AB  - We describe a 6 1/2-year-old girl with the cardio-facio-cutaneous (CFC) syndrome.
      She presents with most of the characteristics of this condition: typical facial
      changes, congenital heart defect, slow growth, ectodermal dysplasia, and
      developmental delay. Chromosome analysis disclosed a 46,XX,inv(7)(q21.2q31.2) mat
      karyotype.

PMID- 8135276
TI  - Cleft palate-lateral synechiae syndrome: report on three new patients with
      additional findings and evidence for variability and heterogeneity.
AB  - We report on 3 Brazilian children with short stature, microcephaly, cleft palate,
      lateral synechiae, and mild mental retardation. One patient was an isolated case
      and the other had an equally affected brother. Genetic aspects and phenotypic
      manifestations are compared with those of previous reports with oral synechiae.
      Recurrence in sibs suggests autosomal recessive inheritance.

PMID- 8135277
TI  - Fetus in fetu: molecular analysis of a fetiform mass.
AB  - Fetus-in-fetu is a rare condition presenting as a calcified intra-abdominal mass
      in the newborn infant. Over 50 cases of fetus-in-fetu have been reported since
      1800. Karyotype analysis in 8 cases and protein polymorphisms in 4 documented
      identical findings in the host and fetiform mass. We report a case of fetus-in
      fetu in a newborn female including cytogenetic and molecular studies of both the
      host and mass. Genotypic information from 7 polymerase chain reaction (PCR)
      assays representing 4 chromosomes demonstrates heterozygous and identical alleles
      in the infant and fetus-in-fetu at all loci studied. A review of the literature
      is provided including a discussion regarding the impact of molecular data on
      present hypotheses of fetus-in-fetu pathogenesis.

PMID- 8135278
TI  - GAPO syndrome in three relatives in a Turkish kindred.
AB  - GAPO syndrome in 2 sibs (brother and sister) and in a first cousin presented
      slight variations in the clinical picture. These include presence of some body
      hair, white eyelashes, deep furrows on sternum and back, disproportional body
      build, and minor skeletal abnormalities. It has been suggested that the athletic
      appearance of affected individuals is most likely due to the excessive amount of
      connective tissue.

PMID- 8135279
TI  - Reproductive failure in a patient with neurofibromatosis-Noonan syndrome.
AB  - We report on a 39-year-old man with neurofibromatosis-Noonan syndrome and long
      standing infertility. Comprehensive testing did not uncover any significant
      endocrine abnormalities, but the testicular seminiferous epithelium was found to
      be severely compromised. While the occasional association of neurofibromatosis
      with signs of Noonan syndrome has been reported, reproductive failure has not
      been previously described in this condition.

PMID- 8135280
TI  - Hypomandibular faciocranial dysostosis: another case and review.
AB  - We report on a third case of hypomandibular faciocranial dysostosis and review
      the literature. Manifestations include craniosynostosis, prominent eyes,
      deficient midface and zygomatic arches, short nose with anteverted nares,
      protruding lower face, minute oral aperture, persistent buccopharyngeal membrane,
      and severe mandibular hypoplasia. In contrast to coronal synostosis found in the
      2 earlier cases, our patient had multiple sutural synostosis. The 2 affected sibs
      reported earlier suggest the possibility of autosomal recessive inheritance.
      However, gonadal mosaicism for a dominant mutation or an undetected microdeletion
      must also be considered at this early stage in the delineation of this disorder.

PMID- 8135281
TI  - Isodicentric X chromosome and mosaicism: report on two cases of
      45,X/46,X,idic(Xq)/47,X,idic(Xq),idic(Xq) and review of the literature.
AB  - We present 2 instances of Ullrich-Turner syndrome with mosaicism
      45,X/46,X,idic(Xq)/47, X,idic(Xq),idic(Xq) and X-isochromosomes with 2 C-bands.
      The mosaicism with the 3 cell lines points to the presence of the isodicentric
      chromosome in the zygote and a subsequent nondisjunction event.

PMID- 8135282
TI  - Congenital central hypoventilation syndrome: inheritance and relation to sudden
      infant death syndrome.
AB  - We evaluated the families of 50 children with idiopathic congenital central
      hypoventilation syndrome (CCHS) to 1) test genetic hypotheses, 2) explore the
      relationship to Hirschsprung disease (HD), and 3) examine other clinical findings
      including sudden infant death syndrome (SIDS) in relatives of CCHS patients. A
      questionnaire was administered to parents of each proband to determine a detailed
      pedigree and medical history for 3 generations including 1,482 relatives. The
      data were analyzed under the unified mixed model method (assumes individual
      genotype composed of multifactorial [MF] and major locus [ML] components).
      Analysis was made of the Total dataset and on subdivided data sets: HIR1 =
      families of probands with HD (n = 8) vs. HIR2 = families of probands without HD;
      then under a premise that severe, chronic constipation may be a milder form of HD
      (i.e., ganglion cells present but dysfunctional), CON1 = families of probands
      with HD or constipation (n = 13) vs. CON2 = families of probands without HD or
      constipation. By statistical genetic analysis of the Total, HIR1, and CON1
      datasets, the MF and ML hypotheses were about equally likely, with the MF model
      slightly more parsimonious. Although HIR2 and CON2 datasets indicated no
      familiality, statistical evidence of heterogeneity between the results of HIR1
      and HIR2, or between CON1 and CON2 was lacking. A SIDS incidence of 11.2/1,000
      was documented among the relatives of CON1 vs. 1.8/1,000 among relatives of CON2.
      Our results are consistent with familiality by either MF or ML models. Recurrence
      risk is likely < 5%. The relationship of CCHS to the high familial incidence of
      SIDS is intriguing and demands further investigation.

PMID- 8135283
TI  - Diagnosis of Huntington disease: a model for the stages of psychological response
      based on experience of a predictive testing program.
AB  - Persons diagnosed as affected with Huntington's disease (HD) may have similar
      stages of psychological response to the clinical presentation of the illness.
      Here we describe a model of these stages of response based on our experience
      during a predictive testing program for HD. During the Warning Stage,
      asymptomatic persons are aware of their risk status for HD and develop defenses
      which favor adaptation to their genetic risk. In response to the initial signs
      and symptoms of HD (the Incipient Stage) unconscious working through of this
      realization occurs while it is still kept out of conscious awareness. When
      symptoms become obvious such that recognition of disease onset is inevitable
      (Breakthrough Stage) the possibility of the diagnosis of HD is assimilated. After
      the delivery of the diagnosis during the Adjustment Stage, short- and long-term
      adaptive responses to living with HD occur. Recognition of the stage of
      psychological response of a patient who presents with HD is important prior to
      delivering a clinical diagnosis. In a significant minority of cases, the
      psychological readiness lags behind the clinical symptomatology and premature
      presentation of a diagnosis may result in significant untoward adverse events.
      Understanding of the stages of response may provide a framework for evaluating
      the psychological state of the person with HD and determining their readiness to
      receiving the diagnosis. This model may have relevance to the psychological
      responses of patients to the diagnosis of other late onset autosomal dominant
      disorders.

PMID- 8135284
TI  - Complex segregation analysis of antibodies to thyroid peroxidase in Old Order
      Amish families.
AB  - Autoimmune thyroid disease (AITD) may be characterized by the measurement in
      serum of antibodies to thyroid peroxidase. A population of Old Order Amish
      individuals and families was investigated to determine the prevalence of these
      antibodies and to examine hypotheses about the mode of transmission of thyroid
      antibodies. Complex segregation analyses were performed on 4 large
      multigenerational Old Order Amish families composed of 26 nuclear families
      containing 199 first degree relatives. Several alternative hypotheses of genetic
      transmission were examined. Hypotheses of no transmission, polygenic inheritance,
      single locus transmission, and mixed inheritance were compared. The analyses
      incorporated population prevalences obtained from a random sample of individuals.
      Results suggest that the pattern of transmission of thyroid antibodies in these
      families is consistent with a mixed model in which the major gene is transmitted
      in an autosomal dominant pattern. The mixed model postulates that there is a
      single gene of major effect as well as a polygenic component that can act
      separately and/or together to confer susceptibility for this phenotype. The
      parameter estimates for the major locus are: gene frequency (q), 0.16 +/- 0.01;
      maximum male penetrance, 0.35; and maximum female penetrance, 0.70. The
      heritability of the polygenic background is estimated at 0.41.

PMID- 8135285
TI  - Interstitial duplication of 7(q22-->q34).
AB  - We report on a 3-year-old boy with an interstitial duplication of 7(q22-->q34),
      confirmed with fluorescent in-situ hybridization. He had post-natal growth
      retardation, developmental delay, frontal and parietal bossing, deep-set eyes,
      strabismus, bilateral optic nerve hypoplasia, and mild dilatation of the cerebral
      ventricles. His phenotype was not significantly different from that of the three
      previously reported patients with interstitial duplication of the smaller segment
      7(q22-->q31).

PMID- 8135286
TI  - Genetic syndromes and uniparental disomy: a study of 16 cases of Brachmann-de
      Lange syndrome.
AB  - Uniparental disomy is responsible for a proportion of cases in Prader-Willi,
      Angelman, and Wiedemann-Beckwith syndromes. In these syndromes, the chromosomes
      involved are thought to contain one or more imprinted genes. When two copies of
      the imprinted (inactivated) gene are inherited from a single parent through
      uniparental disomy or the active gene is deleted, the phenotype of the syndrome
      results. Our goal is to identify additional syndromes caused by uniparental
      disomy. Our approach is to select syndromes that appear to have more than one
      mode of inheritance and are occasionally associated with a cytogenetic
      abnormality. Given this criterion, we have chosen Brachmann-de Lange Syndrome
      (BDLS) to investigate since the phenotype is similar to that found in patients
      with dup(3q). We have studied 16 probands with BDLS and their parents using a
      multiplex of four PCR-based polymorphic loci on chromosome 3. None of the
      probands studied had uniparental disomy for chromosome 3 and all demonstrated
      normal biparental inheritance for at least one locus. Given these results,
      uniparental disomy of chromosome 3 does not appear to be a major contributor to
      the syndrome. Additionally, both maternally and paternally derived chromosome
      abnormalities have resulted in the dup(3q) phenotype and dominant inheritance of
      BDLS from both mildly affected mothers and fathers have been reported which
      suggests that imprinting is not involved in these syndromes.

PMID- 8135287
TI  - Two sibs with different phenotypes due to adjacent-1 segregation of a subtle
      translocation t(4;5)(p16.3;p15.3)mat.
AB  - High-resolution chromosome banding and in situ hybridization with combined cosmid
      and alphoid sequence probes were used to delineate a very small reciprocal
      translocation in a mother and her two children. The first child has a
      46,XX,der(4)t(4;5)(p16.3;p15.3)mat and thus has a deletion of 4p16.3-->pter and a
      duplication of 5p15.3-->pter (most likely 5p15.31-->pter). Clinical findings
      include marked growth retardation, developmental delay, seizure disorder,
      microcephaly, unruly hair, broad nasal tip, downturned mouth, narrow palate, 11
      pairs of ribs, mild right club foot, and a deep sacral dimple. Thus, this child
      has only a few non-specific manifestations of Wolf-Hirschhorn syndrome. The
      second child has a 46,XY,der(5)t(4;5)(p16.3;p15.3)mat; thus a deletion of 5p15.3-
      >pter and a duplication of 4p16.3-->pter. He has failure to thrive, developmental
      delay, microcephaly, sparse hair, horizontal nystagmus, short upturned nose with
      flared nostrils, thin lips with overhanging upper lip, long fingers and toes, and
      hypertonicity. Findings in the second patient are not suggestive of cri du chat
      syndrome (del 5p). The mother is phenotypically normal. This translocation will
      be useful in mapping genes and markers on the 4p and 5p chromosomal regions.

PMID- 8135288
TI  - Mucolipidosis type IV: a mild form with late onset.
AB  - A 16-year-old girl is presented with mild clinical manifestations and late onset
      of mucolipidosis type IV (MLIV). The patient, an Ashkenazi Jew, has had minor
      motor difficulties and mild psychological disturbances since early childhood. Her
      vision began deteriorating at 12 years of age, due to bilateral corneal opacities
      and retinal degeneration. At present she attends a regular high school, although
      she is slow and scholastic achievements are lower than average. Electron
      microscopic examination and biochemical studies were typical for MLIV, namely,
      abnormal ganglioside retention and typical pattern of phospholipids accumulation.
      This very mild presentation of MLIV suggests a broader spectrum of heterogeneity
      of this disorder and raises the possibility that MLIV, at least among Ashkenazi
      Jews, might be more frequent than estimated hitherto, due to undiagnosed mild
      patients.

PMID- 8135289
TI  - "Holoprosencephaly-polydactyly" (pseudotrisomy 13) syndrome: expansion of the
      phenotypic spectrum.
AB  - Analysis of familial cases of the so called "holoprosencephaly-polydactyly"
      ("pseudotrisomy 13") syndrome shows that neither holoprosencephaly, nor
      polydactyly are obligatory manifestations of this condition. This review of
      previous case reports shows that each of these anomalies is only found in
      approximately 60% of affected sibs, and therefore these sentinel abnormalities
      are not required for diagnosis. We propose a widening of the phenotypic spectrum
      of this syndrome and consideration of the use of an eponomic name, such as the
      Cohen-Gorlin syndrome, or clear recognition that the sentinel findings of
      holoprosencephaly and polydactyly are not essential for diagnosis. We propose the
      following diagnostic criteria for the syndrome. The diagnostic criteria for
      sporadic cases would include a normal karyotype and either (1) a combination of
      holoprosencephaly and post-axial polydactyly with or without other
      characteristics, or (2) a combination of holoprosencephaly with other
      characteristics but without polydactyly, or (3) a combination of postaxial
      polydactyly, brain defects (microcephaly, hydrocephaly, agenesis of corpus
      callosum) and other characteristics. The diagnostic criteria for the familial
      cases would be the same, except that, as long as the other sibs have no
      abnormalities contradicting the diagnosis, a normal karyotype would be required
      in only one affected sib.

PMID- 8135290
TI  - Autosomal imbalance syndromes: genetic interactions and the origin of congenital
      malformations in aneuploidy syndromes.
AB  - In some autosomal imbalance syndromes an additional imbalance interferes with the
      occurrence of the anomalies typical of the syndrome itself. For example,
      polydactyly was found in patients with "pure" del(3p) more frequently (11/23)
      than in patients where these deletions were associated with different partial
      trisomies (2/28). The opposite situation was shown in del(7q) syndrome where
      various defects of the holoprosencephalic group were found to be rarer in
      patients with "pure" deletions, than in cases with simultaneous occurrence of
      various partial trisomies. It suggests the importance of gene interaction in
      determining the phenotypic picture of autosomal imbalance syndromes.

PMID- 8135291
TI  - Thyroid dysgenesis and the dysplasia hypothesis in tuberous sclerosis.
AB  - Thyroid dysfunction is rare in tuberous sclerosis, although papillary adenomas
      (hamartomas) of the thyroid gland have been reported in a few autopsy cases. We
      describe a child with tuberous sclerosis and primary congenital hypothyroidism
      secondary to a dysgenetic thyroid gland. To our knowledge, this association has
      not been reported previously. Although the association of these two disorders in
      one patient may be merely coincidence, we speculate that the dysgenetic thyroid
      gland in this patient may represent a "hamartia" as a consequence of the tuberous
      sclerosis gene.

PMID- 8135292
TI  - Cerebro-reno-digital syndrome in two sibs.
AB  - We describe two sibs with mental retardation, facial anomalies, polydactyly,
      cerebellar vermis agenesis, and either meningocele or renal cystic dysplasia. The
      patients' condition appears to belong to a group of cerebro-reno-digital
      syndromes. Autosomal recessive inheritance is suggested.

PMID- 8135293
TI  - Lower lip pits and complete idiopathic precocious puberty in a patient with
      Kabuki make-up (Niikawa-Kuroki) syndrome.
AB  - We report on a 13 1/2-year-old patient with Kabuki make-up syndrome and complete
      idiopathic precocious puberty manifested at 7 1/2 years. In addition to the other
      specific clinical signs, she showed hypodontia and lower lip pits, as typically
      seen in the Van der Woude syndrome. The significance of lower lip pits in the
      Kabuki make-up syndrome is discussed.

PMID- 8135294
TI  - Prenatal diagnosis of nonrhizomelic chondrodysplasia punctata (Conradi-Hunermann
      syndrome).
AB  - Chondrodysplasia punctata has been classified into two major types including the
      rare autosomal recessive "rhizomelic type" and a more common but genetically
      heterogenous nonrhizomelic type (referred to by some authors as "Conradi
      Hunermann (CH) type"). The former is typically lethal, manifesting serious
      anomalies, and allowing several instances of confident prenatal diagnosis. The
      latter being milder has more subtle anomalies and prenatal diagnosis has been
      uncommonly reported (confined to cases diagnosed incidentally by flat-plate X-ray
      examination of the mother in late third trimester, and a case found by directed
      ultrasound performed in a Mendelian affected mother). Cases included 1) a young
      primigravida thought to be affected with Conradi-Hunermann syndrome presented at
      16 weeks gestation for prenatal diagnosis and counseling. Ultrasound examination
      of the fetus detected assymetric limb shortness allowing the presumptive
      diagnosis of an affected fetus which was confirmed after delivery near term. 2) A
      normal 38-year-old multipara with unremarkable family history underwent routine
      fetal ultrasound evaluation at 18 weeks gestation. Disorganization of the spine,
      premature echogenicity of femoral epipheses, and frontal bossing with depressed
      nasal bridge were described. Neonatal examination confirmed suspicion of CH. Case
      1 demonstrates the importance of solid clinical diagnosis in Mendelian
      malformation-affected parents for directing prenatal diagnostic efforts. Case 2
      represents the first index case of CH diagnosed antenatally by ultrasound.
      Diagnostic clues which must be considered in establishing these diagnoses are
      discussed, as are some of the difficulties and limitations in antenatal
      counseling such cases.

PMID- 8135295
TI  - Does ascertainment bias contribute to the reported association of omphalocele and
      gastroschisis with other birth defects in families but not in individuals?

PMID- 8135296
TI  - Atrioventricular canal and 8p- syndrome.

PMID- 8135297
TI  - Ankyloblepharon filiforme adnatum and imperforate anus: a new family with
      apparently autosomal dominant inheritance.

PMID- 8135299
TI  - Stuttering: a complex behavioral disorder for our times?

PMID- 8135298
TI  - Prenatal diagnosis of Charcot-Marie-Tooth disease type 1A by multicolor in situ
      hybridization.
AB  - Genetic heterogeneity within the most common genetic neuropathy, Charcot-Marie
      Tooth disease (CMT) results in about 70% slow nerve conduction CMT1 and 30%
      normal nerve conduction CMT2. Autosomal dominant CMT1A on chromosome 17p11.2
      represents about 70% of CMT1 cases and about 50% of all CMT cases. Three
      different size CMT1A duplications with variable flanking breakpoints were
      characterized by multicolor in situ hybridization and confirmed by pulsed field
      gel electrophoresis and quantitative polymerase chain reaction (PCR)
      amplification. These different size duplications result in the same CMT1A
      phenotype confirming that trisomy of a normal gene region results in CMT1A. The
      smallest duplication does not include the 409 locus used previously to screen for
      CMT1A duplications. Direct analysis of interphase nuclei from fetuses and at-risk
      patients by multicolor in situ hybridization to a commonly duplicated CMT1A probe
      is informative more often than polymorphic PCR analysis, faster than pulsed field
      gel electrophoresis (PFGE), and faster, more informative, and more reliable than
      restriction enzyme analysis. CMT1B restriction enzyme analysis of CMT pedigrees
      without CMT1A is expected to diagnose another 8% of at-risk CMT1 patients (total:
      78%).

PMID- 8135300
TI  - Stuttering as a phenotype for behavioral genetics research.
AB  - Stuttering is a broad behavioral phenotype with an adult prevalence of 0.7-1.0%.
      Family, twin, and segregation studies all indicate that stuttering has a large
      genetic component to its etiology. The relatively simple phenotype, the early
      onset, and the apparent rarity of phenocopies of adult stuttering all make
      stuttering a promising model for the study of the genetics of broad behavioral
      phenotypes.

PMID- 8135301
TI  - Mutational analysis of candidate genes in psychiatric disorders.
AB  - A genetic hypothesis for a disease presupposes the existence of variation in the
      DNA sequences of affected individuals. A series of techniques known together as
      "mutational analysis" can be applied towards identifying new sequence variations
      in selected genes. These techniques can screen a large series of individuals for
      mutations efficiently, so it is not necessary to determine the nucleotide
      sequence in every DNA sample. DNA samples suspected of harboring sequence
      variants are then sequenced. Denaturing gradient gel electrophoresis techniques,
      single stranded conformation polymorphism paradigms, and chemical cleavage of
      mismatches are 3 procedures widely used for the molecular screening of mutations
      today. We discuss each of these techniques for mutation screening.

PMID- 8135302
TI  - Unipolar relatives in bipolar pedigrees: a search for indicators of underlying
      bipolarity.
AB  - In an effort to identify features indicative of underlying bipolarity within the
      unipolar relatives of bipolar probands, we compared unipolar relatives of
      bipolars with unipolar relatives of unipolars. Using data from the Collaborative
      Study of the Psychobiology of Depression, we compared a number of demographic and
      clinical features individually, and then developed a logistic regression model
      for the differences found. Unipolar relatives of bipolars were somewhat more
      likely to be male and to have subthreshold bipolar features, and less likely to
      have panic symptoms. In addition, they had a small but significant decrease in
      the number of depressive symptoms and a large decrease in all treatment
      indicators. A multiple logistic regression model for these differences was highly
      significant, but had limited ability to discriminate between the two groups.
      These differences are not large enough to effectively discriminate between the
      groups for the purposes of classification. These particular results may result
      from a number of factors, most likely the choice of comparison group.
      Nonetheless, the work demonstrates a potential method for the construction of
      caseness indices for use in genetic studies of bipolar and other psychiatric
      disorders.

PMID- 8135303
TI  - Association of monoamine oxidase (MAO) activity with alcoholism and alcoholic
      subtypes.
AB  - A familial/genetic study of platelet monoamine oxidase (MAO) activity in
      alcoholics was carried out. MAO activities were determined using phenylethylamine
      (PEA) as substrate at Km concentration (1.2 microM) and at saturating
      concentration (12.0 microM). Complex segregation analysis of familial data
      indicated a single major gene mode of transmission of activity at both substrate
      concentrations. In addition, the present sample size (13 families, 108 members)
      proved sufficient to allow correlation analysis of enzyme activity with affection
      status and clinical subtypes of affecteds. MAO activity was significantly
      correlated with alcoholism at both Km and saturating substrate concentrations and
      a significant correlation between low MAO activity and Cloninger Type II
      alcoholism was seen at Km substrate concentration. These results confirm a
      hierarchical cosegregation of platelet MAO activity and alcoholism suggesting
      that MAO activity warrants continued status as a marker in alcoholism.

PMID- 8135304
TI  - Association study of schizophrenia with dopamine D3 receptor gene polymorphisms:
      probable effects of family history of schizophrenia?
AB  - Using a case-control design, a reported association of schizophrenia with
      homozygosity at the dopamine D3 receptor gene locus was investigated in a group
      of patients (n = 53), with schizophrenia (DSM-III-R), and psychiatrically normal
      controls (n = 61), matched for ethnicity and area of residence. No significant
      differences in the distribution of alleles or genotypes between the two groups
      could be detected. However, among patients with a family history of
      schizophrenia, as compared to controls without such family history, an
      association with allele 1 at this locus was noted (Odds ratio 12.4, C.I. 1.61,
      96.35).

PMID- 8135305
TI  - Alleles at the dopamine D4 receptor locus do not contribute to the genetic
      susceptibility to schizophrenia in a large Swedish kindred.
AB  - The discovery of a functional polymorphism within the dopamine D4 receptor gene
      (DRD4) has not only strengthened the hypotheses implicating DRD4 in the etiology
      of neuropyschiatric disorders, but also provided a genetic marker for testing
      these hypotheses. The possibility of the dopamine D4 receptor as a candidate gene
      for schizophrenia was investigated in a large Swedish kindred segregating for
      schizophrenia. Linkage to schizophrenia was tested by linkage analyses of 6
      polymorphic markers (at 4 loci) in chromosome 11p15.5 including the dopamine D4
      receptor (DRD4) and the tyrosine hydroxylase (TH) loci. Schizophrenia was
      excluded from close linkage to the DRD4 locus using two of the polymorphisms
      located within the dopamine D4 receptor gene. The first DRD4 polymorphism
      consists of variation in the number of a 48 bp imperfect direct repeat in the
      third exon; the second consists of a variable number of repeated G nucleotides in
      the first intron. In addition, some of the individuals homozygous for four or
      seven copies of 48 bp repeat alleles were tested for previously reported sequence
      variation among repeats. No single haplotype of the DRD4 alleles or haplotype of
      other markers in chromosome 11p15.5 was found to be common to the schizophrenic
      individuals in this family. Therefore, we find no evidence for linkage of the D4
      receptor, or this region of 11p15.5, with genetic susceptibility to schizophrenia
      in this kindred.

PMID- 8135306
TI  - Risk factors for suicide in Huntingtons disease: a retrospective case controlled
      study.
AB  - We reviewed 11 instances of suicide in HD families to determine what clinical and
      social characteristics might alert health professionals to increased suicide
      potential. The subjects were eight males and one female affected with HD, one
      female at risk for HD, and one unaffected female spouse, ranging in age from 24
      to 65 years. Six of the nine individuals with HD who committed suicide were
      single or divorced. Duration of HD symptoms ranged from 1 to 14 years. The single
      most important risk factor for suicide in HD was having no offspring. Other
      suicides in the family, being unmarried, having contact with others affected with
      HD, living alone, and depression slightly increased the risk of suicide. The
      suicide of an unaffected spouse and an individual at risk, but unaffected,
      emphasizes the heavy burden of HD on other family members. Recognition of these
      risk factors should allow health care providers to assist families coping with HD
      and presymptomatic diagnosis.

PMID- 8135307
TI  - National Health Care Reform. What are the Issues? Where are we Going? Newark, New
      Jersey, April 30-May 1, 1993.

PMID- 8135308
TI  - Health care reform: identifying some cost culprits.
AB  - In terms of both total cost and fraction of the gross national product, the cost
      of health care in the United States is considerably greater than anywhere else in
      the world. The reasons for the excessively high cost are complex and include
      issues of administration, issues of quality, and issues peculiar to American
      culture. Some contributing factors are the demographics of the population, the
      cost of defensive medicine and litigation, costly regulation, extensive
      application of technology in response to public demand and expectations, and
      finally, waste and abuse of the system. Control of costs cannot realistically be
      achieved by simply changing the way we finance health care, but will require
      changing the economic incentives for both providers and patients. Reforming the
      system will necessarily include compromising some of our expectations about
      health care, changing unhealthy lifestyles, and more realistically analyzing the
      costs of litigation and regulations.

PMID- 8135309
TI  - Reflections on national health care reform based on Hawaii's experience.
AB  - In 1974, Hawaii began addressing the problem of health care accessibility. As a
      result of legislative action, near universal health care coverage has been
      achieved. These include employer mandates to provide adequate health insurance,
      regulation of insurance products, control of costly health care facilities, and
      government assistance to those not provided health insurance through employment.
      By providing primary care, total health care costs are considerably below
      national average--even though actual cost of living is over 30% greater. Public
      health statistics suggest a healthier population than the national average. This
      cannot be attributed to a healthy or relaxed lifestyle or ethnic mix, but rather
      to the state health care system itself. Economically and culturally, Hawaii
      closely resembles the rest of the United States, and there has been no evidence
      of reduced employment due to the aforementioned employer mandate.

PMID- 8135310
TI  - Survey of health planning proposals.
AB  - It is important that physicians participate in the debate and planning process
      that will ultimately guide how we reform the way health care is financed and
      delivered in the United States. Herein is offered a perspective on the problem,
      one which is not necessarily appreciated by health planners. While we deliver the
      best quality of care in the world to most of our population, our system has been
      severely criticized because we fail to provide for access to a substantial
      minority of our population. Additionally, the cost of the product is considerably
      greater than that in comparable countries. Attempts to control costs without
      diminishing quality have introduced expensive complexities into our system
      without any real success in cutting costs. Several proposals have been advanced
      to address the issues of cost and access. One of these is a single payer system,
      common in Europe and Canada, whereby a single agent or group of agents finances
      all health care through universal rules and means. A system operating in Hawaii
      is a simple employer mandate to provide health insurance. A uniquely American
      plan is the Jackson Hole Plan or Managed Competition (now called "Managed
      Cooperation"). This system is currently popular among national health planners,
      and involves a defined minimum managed health plan offered by various groups of
      providers to employees and individuals through health plan purchasing
      cooperatives. This plan is interesting, but has not been implemented in any
      jurisdiction, and it is not certain it would accomplish its goals in practice
      since it is difficult to predict behavior of all parties to such a system.

PMID- 8135311
TI  - Economics of health care reform.
AB  - Several economic points require consideration when assessing the current cost of
      health care in the United States and the potential savings from proposed reforms.
      Most savings projections are based on assumptions and estimates that cannot be
      accurate under the best of circumstances, and the error in the final results is
      greatly compounded by even small errors in the initial estimates. Experience with
      health care programs worldwide, including our own Medicare program, has shown
      that final costs are usually much larger--often several times larger--than
      initial estimates. It is even more difficult to predict the behavior of the
      population under a system that does not yet exist, and it is not clear whether a
      system such as the Jackson Hole Plan will actually produce savings. The effect of
      our political system will have on any health system enacted through legislation
      must also be considered. The political process itself frequently results in more
      benefits rather than fewer, more regulation rather than less, and the shifting of
      costs to other sectors of the economy to minimize costs in the health sector.
      When presented with projections and predictions in health care planning, we must
      critically examine the initial assumptions, knowing that errors in these
      assumptions will magnify errors in the final results.

PMID- 8135312
TI  - Health systems planning at a state level: New Jersey.
AB  - In 1991, New Jersey undertook a planning effort to eliminate the proliferation of
      high cost, redundant services, downsize or eliminate underutilized services,
      develop primary and preventive services, and consolidate regional services. The
      recommendation to reduce the number of accredited hospitals created serious
      opposition from a variety of interests and the legislature subsequently enacted
      legislation prohibiting enactment of rules to implement the plan. More recently,
      New Jersey undertook new legislation to reform health insurance to require
      community rating, availability of individual and small group policies, eliminate
      restriction on pre-existing conditions, and promote competition. Legislation also
      provided for hospital care of indigents to be funded by a change in the
      unemployment insurance system. The latter was to replace a funding mechanism
      which was initially invalidated by a Federal Court. In future years, some of
      these funds will be shifted to a subsidized insurance program. There is already
      evidence that these reforms have resulted in increased competition among
      insurance companies, hospitals, and providers. Hopefully, this will contain costs
      without a decrement to quality. It should also increase the number of people with
      health coverage, although this does not provide for universal coverage.

PMID- 8135313
TI  - Economic and medical directions in the Czech Republic and Hungary.

PMID- 8135314
TI  - Pneumonia in the surgical intensive care unit: factors determining successful
      outcome.
AB  - A review of 85 consecutive patients who acquired pneumonia in a surgical
      intensive care unit revealed several parameters associated with successful
      treatment. Fifty-five patients (65%) recovered after a single course of
      antimicrobial therapy. Statistical analysis demonstrated significant differences
      between those treated successfully and those whose therapy failed during the
      duration of intubation (7.2 +/- 1.5 days versus 29.3 +/- 4.3 days), duration of
      ventilation (6.7 +/- 1.4 days versus 14.8 +/- 3.2 days), and the alveolar
      arterial oxygen gradient on the day of diagnosis (215 +/- 23 mm Hg versus 343 +/-
      33 mm Hg, all p < 0.01). Multiple antimicrobial resistance was uncommon in
      bacteria isolated on initial culture but occurred in two thirds of patients with
      treatment failures. Pneumonia due to Pseudomonas aeruginosa and Staphylococcus
      aureus were associated with the highest rate of treatment failure, which were 56%
      and 45%, respectively.

PMID- 8135315
TI  - Association of perioperative transfusions with poor outcome in resection of
      gastric adenocarcinoma.
AB  - The clinical records of patients identified by a prospective database as having
      undergone curative gastric resections for adenocarcinoma not involving the
      gastroesophageal junction were reviewed in order to examine transfusional
      practices and to determine if perioperative transfusion had an adverse effect on
      outcome. Between January 1985 and January 1992, 232 patients received such
      curative resections. The median follow-up for these patients was 19.0 months,
      whereas median survival for nonsurvivors was 12.3 months. Fifty-eight percent of
      the patients received transfusion of blood products. Fifty-four percent of these
      transfusions amounted to less than 2 units of blood products. By chi 2 analysis,
      advanced stage of disease (p = .03), advanced T-stage of primary tumor (p =
      .004), and total gastrectomy (p = .04) were associated with greater likelihood of
      transfusion. By univariate analysis, male sex (p = .004), total gastrectomy (p =
      .01), advanced stage of disease (p = .000006), high histologic grade of tumor (p
      = .03), and blood transfusion (p = .006) were predictors of poor outcome. By
      multivariate analysis using the proportional hazards model with stage, tumor
      grade, gender, extent of resection, and transfusion as covariates, blood
      transfusion was an independent predictor of poor outcome (p = .029, hazard 1.74).
      These results encourage prospective studies of transfusion on cancer recurrence
      and studies of alternatives to allogeneic blood transfusions in restoration of
      oxygen-carrying capacity during surgery in patients with gastric cancer.

PMID- 8135316
TI  - Normal pancreatic dimensions in the adult human.
AB  - Thirty cadaver pancreas specimens were dissected and carefully measured. The
      weights were recorded and averaged 91.8 g (range: 40.9 to 182 g). The glands were
      then divided into three segments using the common bile duct of the portal vein as
      sites of transection, and the various specimens were weighed. The data suggest
      that a pancreatectomy done to the left of the common bile duct will remove 90% of
      the gland and resection done to the left of the portal vein will remove about 60%
      of the gland. It is hoped that these data will be useful to surgeons in
      estimating the magnitude of pancreatic resection.

PMID- 8135317
TI  - Prostaglandin E2 levels and lymphocyte subsets in portal venous drainage of
      colorectal cancers.
AB  - Local immunosurveillance may play an important role in the growth and spread of
      tumors. To investigate the local immune response, we determined prostaglandin E2
      (PGE2) levels (n = 23) and lymphocyte subsets (n = 10) in the portal vein
      draining the tumors of patients with colorectal cancer. PGE2 levels in the portal
      vein were significantly higher than those in the radial artery. Portal PGE2
      levels in patients with advanced stage tumors (Duke's C and D) and lymph node
      metastases were significantly higher than those of patients with Duke's A and B
      tumors without lymph node metastases. Moreover, four of the nine patients with
      portal PGE2 levels greater than 100 pg/mL had liver metastases within 2 years of
      surgery. There were no differences in lymphocyte subsets between the portal vein
      and the radial artery. PGE2 levels in the portal vein draining colorectal tumor
      may thus be closely related to tumor progression and recurrence and may serve as
      a predictor of tumor recurrence in patients with colorectal cancer.

PMID- 8135318
TI  - Nosocomial blood-borne infection secondary to intravascular devices.
AB  - A total of 143 patients with 159 episodes of intravascular device, blood-borne
      infection were studied. All infections were confirmed by the same organism being
      recovered from blood culture and by semiquantitative culture of the catheter tip.
      Sites of infection included the peripheral venous line (n = 72), central catheter
      (n = 49), arterial line (n = 18), subclavian dialysis catheter (n = 12), Swan
      Ganz catheter (n = 4), Broviac catheter (n = 3), and transvenous pacemaker wires
      (n = 1). Staphylococcus aureus (n = 78) and Staphylococcus epidermidis (n = 33)
      predominated as pathogens. Excessive length of catheterization was implicated as
      directly responsible for this complication in patients with peripheral
      intravenous and arterial lines. Nosocomial staphylococcal bacteremia must be
      considered secondary to an indwelling intravascular device until proven
      otherwise. Appropriate therapy requires removal of the catheters, excision of the
      vein if suppuration or persistent bacteremia is identified, and specific
      antibiotic therapy.

PMID- 8135319
TI  - Laparoscopic gastrostomy using four-point fixation.
AB  - Percutaneous endoscopic gastrostomy (PEG) has become an effective alternative to
      surgical gastrostomy in patients who require enteral access or gastric
      decompression. Technical considerations, however, limit the application of PEG in
      selected patients and those who have contraindications to PEG. Laparoscopic
      gastrostomy tube placement has been introduced as an alternative to PEG. A
      technique for laparoscopic gastrostomy tube placement that emphasizes four-point
      fixation of the anterior gastric wall is presented.

PMID- 8135320
TI  - A simple method to control intractable bleeding after endoscopic sphincterotomy.
AB  - A successful method for controlling intractable bleeding after endoscopic
      sphincterotomy is described. By passing a Fogarty catheter into the duodenum,
      balloon tamponade of the bleeding point is possible. By such a technique, major
      resective surgery can be avoided.

PMID- 8135321
TI  - Prepyloric antrectomy, truncal vagotomy, and front pylorotomy for the treatment
      of duodenal ulcer.
AB  - We have performed a suprapyloric antrectomy with anterior pylorotomy and truncal
      vagotomy in 106 patients with chronic duodenal ulcer between 1975 and 1990.
      Follow-up was carried out in 94 patients, during a mean time of 6 years. We have
      had no postoperative mortality and no long-term recurrence. The percentage of
      Visick I patients is similar to that after truncal vagotomy and antrectomy. We,
      therefore, believe that this procedure is safe and can be performed when an
      antrectomy is mandatory to avoid the operative morbidity and mortality of classic
      antrectomy.

PMID- 8135322
TI  - Physiologic effects of pneumoperitoneum.
AB  - Laparoscopy requires the establishment of pneumoperitoneum in order to provide
      adequate surgical exposure and maintain operative freedom. Insufflation of carbon
      dioxide into the peritoneal cavity, however, can affect several homeostatic
      systems, leading to alterations in acid-base balance, blood gases, and
      cardiovascular and pulmonary physiology. Although these changes may be well
      tolerated by healthy individuals, they may increase physiologic stress in
      patients with pre-existing conditions, placing them at increased risk for
      perioperative complications. An understanding of the physiologic changes caused
      by carboperitoneum is therefore essential for identification of high-risk
      patients and formulation of appropriate treatment plans, which may include
      preoperative cardiorespiratory optimization and perioperative monitoring. Under
      optimal conditions, debilitated patients should be able to tolerate
      pneumoperitoneum safely and, thereafter, reap the benefits associated with
      minimally invasive surgery.

PMID- 8135323
TI  - Managing the aspirating patient.

PMID- 8135324
TI  - Sinopulmonary relationships.

PMID- 8135325
TI  - Oral magnesium intake reduces permanent hearing loss induced by noise exposure.
AB  - INTRODUCTION: Following animal experiments where correlations were observed
      between serum magnesium level and noise-induced permanent hearing threshold
      shifts (NIPTS), we tested the prophylactic effect of magnesium in human subjects
      exposed to hazardous noise. METHODS: Subjects were 300 young, healthy, and normal
      hearing recruits who underwent 2 months of basic military training. This training
      necessarily included repeated exposures to high levels of impulse noises while
      using ear plugs. During this placebo-controlled, double-blind study, each subject
      received daily an additional drink containing either 6.7 mmol (167 mg) magnesium
      aspartate or a similar quantity of placebo (Na-aspartate). RESULTS: NIPTS was
      significantly more frequent and more severe in the placebo group than in the
      magnesium group, especially in bilateral damages. NIPTS was negatively correlated
      to the magnesium content of blood red cells but especially to the magnesium
      mononuclear cells. Long-term additional intake of a small dose of oral magnesium
      was not accompanied by any notable side effect. CONCLUSION: This study may
      introduce a significant natural agent for the reduction of hearing damages in
      noise-exposed population.

PMID- 8135326
TI  - Squamous cell carcinoma of the nasal vestibule and anterior nasal passages.
AB  - PURPOSE: This retrospective review of nasal vestibule and anterior nasal cavity
      squamous cell carcinomas correlates clinical presentation, methods of treatment,
      and histologic differentiation with outcome. PATIENTS AND MATERIALS:
      Epidemiologic data, patient history, and physical findings for 25 cases are
      presented. Cigarette usage was prevalent in this group, as it is in most series
      of patients with epithelial tumors of head and neck locations. Treatment was
      surgery alone (n = 10), irradiation (n = 4), or combined therapy (n = 11).
      RESULTS: Combined surgery and postoperative irradiation yielded better recurrence
      free survival than either treatment used alone. CONCLUSIONS: Although the series
      studied was small and the selection criteria for treatment were not uniform, this
      retrospective study supports wide surgical resection combined with postoperative
      irradiation as the preferred treatment of squamous cell carcinoma of the nasal
      vestibule with extension to adjacent areas. However, treatment should be
      individualized to provide the greatest chance for cure while preserving nasal
      form and function as far as is possible in each patient.

PMID- 8135327
TI  - Relationship between outer ear resonance and permanent noise-induced hearing
      loss.
AB  - INTRODUCTION: Prolonged exposure to noise produces permanent hearing loss in the
      frequency region centered around 4,000 Hz despite differences in the spectral and
      temporal characteristics of the noise. It is unclear to what extent properties of
      the auditory system contribute to the development of permanent hearing loss in
      this frequency region. This study was designed to evaluate the relationship
      between the frequency of peak outer ear resonance and the frequency of maximum
      hearing loss in a population of patients with a history of noise exposure.
      MATERIALS AND METHODS: Analysis of the frequency of maximum hearing loss was
      completed with sweep frequency Bekesy audiometry with resolution of 100 Hz. Peak
      outer ear resonant frequency was determined with a resolution of 175 Hz. RESULTS:
      The mean frequency of maximum hearing loss was 4,481 Hz whereas the mean peak
      outer ear resonant frequency was 2814 Hz for 43 ears. Pearson product correlation
      coefficient equaled .64 (P < .0001). CONCLUSIONS: Despite differences in the type
      and duration of noise exposure reported by the patients, the positive correlation
      between outer ear resonant frequency and frequency of maximum hearing loss
      emphasizes the role that external ear properties play in the development of the
      4,000 Hz audiometric notch.

PMID- 8135328
TI  - Negative findings of esophagoscopy for suspected foreign bodies.
AB  - PURPOSE: Suspected impaction of esophageal foreign bodies may at times pose a
      diagnostic problem as to the decision to perform esophagoscopy. It is not unusual
      to perform a rigid esophagoscopy following a diagnostic work-up for an impacted
      foreign body and not to find one. This study attempts to delineate the clinical
      situations where negative esophagoscopies are more likely to occur. MATERIALS AND
      METHODS: In a retrospective analysis of 98 rigid esophagoscopies performed for
      suspected foreign bodies in our department, an attempt was made to delineate the
      clinical and radiologic findings characteristic of the patients who had no
      foreign body at esophagoscopy compared with the patients in whom a foreign body
      was found. RESULTS: Negative esophagoscopies were associated with suspected bone
      (mostly fish) impaction in 20 of the 22 negative esophagoscopies. Other
      parameters associated with negative findings were prolonged duration of symptoms
      and a positive finding at the physical examination. In suspected bone impaction,
      barium studies and neck x-rays were not helpful in determining the presence of a
      foreign body. CONCLUSION: Clinical history is the main indicator in the decision
      to perform esophagoscopy for suspected foreign bodies.

PMID- 8135329
TI  - Synovial sarcoma of the neck: radiographic findings with a review of the
      literature.

PMID- 8135330
TI  - Mucoepidermoid carcinoma of the mandible.

PMID- 8135331
TI  - Fracture of a synthetic fenestrated tracheostomy tube: case report and review of
      the literature.

PMID- 8135332
TI  - Arytenoid subluxation from blunt laryngeal trauma.
AB  - Isolated arytenoid dislocation and subluxation are uncommon laryngeal injuries
      most often resulting from endotracheal intubation. However, these diagnoses must
      be entertained in all patients having sustained laryngeal trauma. Complaints of
      dysphonia, pain with phonation, or odynophagia in the setting of laryngeal trauma
      should include evaluation for possible arytenoid displacement after an airway is
      secured. Prolonged hoarseness or odynophagia after endotracheal intubation should
      alert the physician to the possibility of a cricoarytenoid joint injury. This
      represents the first reported case of isolated arytenoid injury resulting from
      blunt external trauma to the larynx. The patient had a stable airway without
      intervention, and the displaced joint spontaneously relocated with resolution of
      the cricoarytenoid edema and hemarthrosis. We propose that the cricoarytenoid
      joint was subluxed probably due to edema, hematoma, and/or cricoarytenoid
      hemarthrosis sustained from blunt laryngeal trauma. We furthermore propose that
      some cases of cricoarytenoid subluxation may be treated without operative
      intervention.

PMID- 8135333
TI  - Histopathology update: otomycosis.

PMID- 8135334
TI  - [The influence of age, sex and circadian rhythms on the nasal mucosal in the
      mucociliary clearance].
AB  - We have studied the nasal mucociliary transport in 115 normal persons between 5
      and 85-years-old. Using vegetable charcoal powder method the transport time
      varies between 5 and 18 minutes. The mean transport time was 8.35 +/- 2.6 min.
      Transport time is not variable with age until sixty years, when transport slow
      down. The mucociliary clearance is faster in female (p = 0.018). In these
      individuals the transport time is less in the evening-hours (p = 0.01). In men no
      differences has been noted (p = 0.57).

PMID- 8135335
TI  - [The laryngeal involvement in Kaposi's sarcoma in the acquired immunodeficiency
      syndrome].
AB  - Kaposi's sarcoma (KS) is a malignant vascular neoplasm characterized, in its
      classical form, by a slow evolutive course, beginning in the lower extremities.
      Lately have been reported more and more cases of this entity associated with the
      acquired immunodeficiency syndrome (AIDS), running much more aggressively. In ENT
      pathology are not uncommon this kind of neoplasm in the oral cavity and
      oropharynx. However at larynx's level such descriptions till now had been
      sporadic. The AA. present a KS case sitting in the epiglottis of an AIDS patient.
      They emphasize the importance of a throughout ENT-examination of these patients
      and also remark the necessity of performing various and deep biopsies in order to
      gain a diagnosis that can be relied on. Finally, they review the updated
      management alternatives for this sort of pathology.

PMID- 8135336
TI  - [Lemierre's syndrome. Case report].
AB  - The paper deals with a thrombophlebitis of the internal jugular vein, coming
      after a Plaut-Vincent's angina, associated to septic embolism of the lung. The
      syndrome was first described by Lemierre, in 1936. Together with a survey of the
      cases reported in the last ten years is made.

PMID- 8135337
TI  - [Therapeutic approach, phonatory results and prognostic factors in patients with
      nodules, polyps and Reinke's edema of the vocal cord].
AB  - Retrospective study dealing with 100 cases of nodules, polyps and Reinke's edema
      of the vocal cord, characterizing this pathology classically considered as
      functional. Broad review of the subject's bibliography.

PMID- 8135338
TI  - [The update: treatment of unilateral recurrent paralysis].
AB  - Management of unilateral recurrent palsies is under review since the late 5
      years. Intracordal injection of Teflon has been the best option from the 70s
      onward. With the arrival of other substances the question about which of them
      offers the most confident results is open. Nowadays the reinnervation of the
      larynx either with nerves of the neighbourhood or neuromuscular pedicles takes a
      preferential place. A group of AA. are proposing the so called "laryngeal
      framework surgery", that is to say, the surgery done with elements surrounding
      the larynx, as elective treatment. This paper exposes the several techniques and
      its particularities in order to present a panoramic view of the therapeutical
      issues of recurrential unilateral paralysis.

PMID- 8135339
TI  - [The influence of hypercholesterolemia and noise on human auditory function].
AB  - A cross-sectional study on occupational noise exposure and hypercholesterolemia
      was conducted in a group of 1.209 workers exposed to industrial noise. Clinical
      examinations and audiograms were compared in exposed and not exposed subjects to
      noise. There was a strong relationship between severe noise induced hearing loss
      and hypercholesterolemia in all de workers. But the relationship was not
      convincing when the workers were considered stratified in groups of age, because
      the number of hard of hearing labourers with high levels of cholesterol,
      increases as they get older. The AA, support the point of view that the age is an
      important confounding factor, and in their study there is no relation between
      noise induced hearing loss and hypercholesterolemia.

PMID- 8135340
TI  - Direct sequencing of polymerase chain reaction-amplified DNA.

PMID- 8135341
TI  - Detection of human tRNAs with antisense oligonucleotides.
AB  - Regulated expression and modification of tRNA isoacceptors may play an important
      role in the control of gene expression during such processes as differentiation
      and immune activation. However, the development of techniques for the
      identification and quantitation of multiple tRNA isoaccepting species has been
      hindered by the relative physicochemical similarity among individual isoacceptors
      and their high degree of post-transcriptional modification. We have used
      antisense DNA oligonucleotides derived from the T stem to acceptor stem region of
      six human tRNAs and one murine tRNA to detect individual tRNA isoacceptors in
      slot blots, Northern blots, and dot blots of human tRNA. This hybridization
      protocol was used in combination with tRNA fractionation by electrophoresis on a
      partially denaturing gel by reversed-phase low pressure chromatography and
      reversed-phase HPLC to identify multiple tRNA isoacceptors in a single sample of
      tRNA. Using this technique, it should be possible to monitor changes in the
      cellular tRNA repertoire that may be involved in the regulation of gene
      expression.

PMID- 8135342
TI  - Preparation and use of polyphosphate-modified zirconia for purification of
      nucleic acids and proteins.
AB  - Polyphosphates of chain lengths between 3 and 100 were coupled to porous zirconia
      particles and used for affinity chromatography of nucleic acids and proteins. It
      is demonstrated that single-stranded RNA and DNA are strongly retained on the
      polyphosphate-modified zirconia support, while double-stranded DNA is only weakly
      bound if at all. Protein separation on this packing can be performed by applying
      both high-performance liquid chromatography and batch procedures. The results
      show that polyphosphate-modified zirconia is a useful affinity packing for
      immobilization and purification of biomacromolecules.

PMID- 8135343
TI  - Analysis of recombinant Schistosoma mansoni antigen rSmp28 by on-line liquid
      chromatography-mass spectrometry combined with sodium dodecyl sulfate
      polyacrylamide gel electrophoresis.
AB  - A recombinant Schistosoma mansoni antigen produced in Saccharomyces cerevisiae
      and purified by glutathione-Sepharose affinity chromatography was analyzed by
      tryptic peptide mapping using on-line reversed-phase high-performance liquid
      chromatography pneumatically assisted electrospray mass spectrometry confirming
      the complete primary structure. Partial covalent modification of the single
      cysteine in the protein with glutathione as well as partial dimerization of the
      Cys-containing tryptic peptide was observed. Combining sodium dodecyl sulfate
      polyacrylamide gel electrophoresis under reducing conditions and tryptic
      digestion of the monomeric protein in the gel slice revealed that dimerization
      was occurring during enzymatic digestion. Furthermore, part of the Cys-containing
      fragment was covalently modified with one moiety of beta-mercaptoethanol by the
      electrophoresis sample buffer and five of the seven methionine-containing peptide
      fragments were partially oxidized to the respective sulfoxides. The use of
      capillary columns provided a complete peptide map of rSmp28 on 7 pmol of tryptic
      digest after sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

PMID- 8135344
TI  - Nonradioactive assay for protein phosphatase 2B (calcineurin) activity using a
      partial sequence of the subunit of cAMP-dependent protein kinase as substrate.
AB  - Currently, protein phosphatase 2B (calcineurin) activity is assayed based on
      release of [32P]phosphate from a 19-amino acid peptide (partial sequence of the
      regulatory subunit of cAMP-dependent protein kinase) following its [32P]ATP
      phosphorylation using the catalytic subunit of cAMP-dependent protein kinase.
      This sensitive method consumes a large amount of radioactivity and is therefore
      problematic as a screening method for calcineurin inhibitors. We have developed
      an alternative nonradioactive enzyme assay in which both phosphorylation by
      protein kinase and dephosphorylation by calcineurin are monitored by the
      simultaneous quantitative determination of phosphorylated and non-phosphorylated
      peptide using HPLC on an RP18 column with uv detection. The method allows the
      measurement of enzyme kinetics as well as the characterization of potential
      inhibitors. The method is comparable in sensitivity to the radioactive assay.
      Since calcineurin is commercially available and the substrate can be prepared in
      a sufficient amount, this method can be used for screening purposes. An important
      advantage of this new method, due to the obviation of radioactivity, is the
      facilitation of kinetic determinations at high substrate concentrations and the
      increased specificity (better identification of substrate and product). The
      nonradioactive substrate is very stable and can be stored for months in
      comparison with the 32P-peptide, which has to be freshly prepared every few weeks
      due to the decay of the nuclid.

PMID- 8135345
TI  - A graphical method for determining the number of essential sites in enzymes with
      multiple binding sites for a ligand.
AB  - We offer a novel graphical method for determining the number of essential sites
      in enzymes that contain multiple binding sites for a ligand. This method is
      applicable both to monomeric enzymes containing multiple "unspecific" sites (for
      protons, metal ions, etc.) and to oligomeric enzymes containing multiple
      "specific" sites (for substrates and their cognate analogues). The overall
      procedure is based on some of the intrinsic properties of the general rate
      equation for enzyme-catalyzed reactions involving multiple binding sites for
      ligands as elaborated by W. G. Bardsley and R. E. Childs (Biochem. J., 149, 313
      328, 1975). The experimental protocol involves measurement of initial rates of
      enzyme-catalyzed reactions either at varying concentrations of the substrate or
      at a fixed concentration of the substrate and varying concentrations of effectors
      (activator or inhibitor). The data are analyzed by plotting 1/v[L]p versus [L]
      (for inhibition) and [L]p/v versus 1/[L] (for activation) for different
      (integral) increments of p (such as 0, 1, 2, 3, ... etc.). According to the
      analytical procedure developed herein, the magnitude of p that yields a
      horizontal asymptote on these plots serves as the quantitative measure of the
      number of essential sites in enzyme molecules. By employing this procedure, we
      have been able to quantitatively ascertain the number of essential sites required
      for the activation or inhibition of a variety of monomeric and oligomeric
      enzymes. Among monomeric enzymes we have established that: (i) of the three
      binding sites for linoleic acid in the lipoxygenase molecule, one site is
      essential for catalysis, and the other two sites are inhibitory; (ii) of several
      plausible protonation sites in the alpha-chymotrypsin molecule, only one
      protonation site is required for the activation of the enzyme; and (iii) there
      are two inhibitory sites for guanidine-HCl per ribonuclease A molecule; the
      enzyme is fully inhibited upon binding of guanidine-HCl at any of these two
      sites. Among oligomeric enzymes, we have discerned that: (i) the individual
      subunits of LDH and phosphorylase b are catalytically active, and (ii) the
      catalytic/functional unit of the creatine kinase molecule is likely to be the
      dimeric subunit. The theoretical details leading to the graphical analysis and
      its usage in delineating the functional stoichiometry of enzyme-ligand complexes
      are discussed.

PMID- 8135346
TI  - A high-throughput assay for cyclic nucleotide phosphodiesterases.
AB  - The search for cyclic nucleotide phosphodiesterase inhibitors in large chemical
      and natural product libraries is limited by assay throughput. A high-throughput
      assay that can monitor different phosphodiesterase activities would be useful for
      these inhibitor searches. We have developed a sensitive phosphodiesterase assay
      which is based on the selective precipitation of the radiolabeled 5'-nucleotide
      product by zinc and barium. This assay is unique to previous precipitation
      methods in that it measures product formed, either GMP or AMP. The procedure was
      adapted to a microtiter plate format for high-throughput, making it possible to
      perform in excess of 960 assays per day. This method was used to determine
      accurate enzyme kinetic constants for three different phosphodiesterases. The
      results agree favorably with literature values. Using the cyclic guanosine 3',5'
      monophosphate-specific phosphodiesterase, IC50 values for the inhibitors M&B
      22,948 and 3-isobutyl-1-methylxanthine were also determined. Demonstration of
      appropriate Km and inhibitor IC50 values verifies the ability of this new assay
      to identify selective cyclic nucleotide phosphodiesterase inhibitors.

PMID- 8135347
TI  - Isolation and characterization of the reaction product of 4-diazobenzenesulfonic
      acid and gamma-carboxyglutamic acid: modification of the assay for measurement of
      beta-carboxyaspartic acid.
AB  - gamma-Carboxyglutamic acid (Gla)-containing proteins are extracellular proteins
      with enhanced cation or mineral-binding properties. Discovery of new Gla
      containing proteins is facilitated by methods that decrease the number of steps
      and time involved in assaying for Gla. Reaction of 4-diazobenzenesulfonic acid
      (DBS) and Gla or Gla-containing proteins produces an intensely red-colored
      product. This method has been used to identify Gla-containing proteins in crude
      extracts of proteins. The reaction product of Gla and DBS has been purified by
      reversed-phase HPLC and characterized by uv-visible spectroscopy and electrospray
      ionization (ESI) mass spectrometry (MS). The red-colored product exhibits an
      absorption maximum at 530 nm. The ESI-MS data of the colored derivative of Gla
      are consistent with replacement of the two gamma-carboxyl groups in Gla with two
      DBS groups. DBS also reacts with another malonic acid derivative, beta
      carboxyaspartic acid (Asa). The optimum conditions for colorimetric assay of Asa
      were established, and the potential of this reaction as an assay for Asa and Asa
      containing proteins was studied.

PMID- 8135348
TI  - 9-Fluorenylmethoxycarbonyl (Fmoc)-glycine coupling of saccharide beta
      glycosylamines for the fractionation of oligosaccharides and the formation of
      neoglycoconjugates.
AB  - We have devised a new saccharide derivatization scheme to provide not only the
      temporary attachment of a chromophore for detecting and facilitating the
      chromatographic separation of carbohydrates, but also the intermediates for
      further derivatization to produce neoglycoconjugates. Several neutral unprotected
      saccharide beta-glycosylamines were formed by the direct condensation of the
      reducing saccharides with aqueous ammonium bicarbonate. The beta-glycosylamine
      derivatives of N-acetylglucosamine, di-N-acetylchitobiose, and asialo-,
      digalactosylated biantennary complex oligosaccharide were N-acylated separately
      with excess 9-fluorenylmethoxycarbonyl (Fmoc)-glycine. The Fmoc-glycinamido beta
      derivatives of these unprotected saccharides were well separated by normal-phase
      high-performance liquid chromatography and detected by ultraviolet absorption.
      Similar derivatization and fractionation of a partial acid hydrolyzate of chitin
      were equally successful resulting in the separation of Fmoc-glycinamido
      derivatives of di-N-acetylchitobiose to hepta-N-acetylchitoheptaose in the
      hydrolyzate. The reversibility of the Fmoc derivatization was demonstrated by
      treating the Fmoc-glycinamido derivative of N-acetylglucosamine with piperidine
      to generate its 1-N-glycyl-beta-saccharide derivative. The structure and
      stereochemistry of this product was confirmed by proton nuclear magnetic
      resonance spectroscopy. The 1-N-glycyl-beta-saccharide derivatives are stable
      intermediates for the formation of asparagine-linked neoglycoconjugates.

PMID- 8135349
TI  - One-minute high-performance liquid chromatography assay for 5'-nucleotidase using
      a 20-mm reverse-phase column.
AB  - A general procedure is described for developing HPLC-based assays for
      nucleotidases by using a 20-mm C-18 reversed-phase column. The method is applied
      on the determination of pyrimidine 5'-nucleotidase activity in human erythrocytes
      lysate and plasma. The activity is detected using isocratic conditions which
      separate the product (nucleoside) from the substrate (nucleotide) in less than 1
      min with 100 mM potassium phosphate, pH 6.0, at a 2 ml/min flow rate. Nucleoside
      products of the enzymatic reactions are directly quantitated from their
      ultraviolet absorbances. The activity value closely agreed with that determined
      by measuring the production of inorganic phosphate. The method does not require
      prior dialysis of the sample and is 50-fold more sensitive than that based on
      colorimetric measurements of inorganic phosphate. Furthermore, avoiding the use
      of radioactive materials offers significant advantages with respect to commonly
      adopted assays and can be conveniently used for the determination of nucleotidase
      activity from different sources.

PMID- 8135350
TI  - Spectrophotometric substrates for cytosolic epoxide hydrolase.
AB  - In this study, we demonstrate the utility of a broad class of spectrophotometric
      substrates for the assay of cytosolic epoxide hydrolase purified from murine
      liver. These substrates, epoxy esters or carbonates, cyclize spontaneously upon
      or during hydrolysis of the epoxide functionality. The alcohol released by
      cyclization may then be assayed directly or by coupling to a second reaction. The
      alcohol produced, or its secondary reaction products, can be selected to give an
      absorption in the visible or near-uv range of the spectrum. This allows the
      synthesis of a wide variety of useful spectrophotometric substrates. 4
      Nitrophenyl (2S,3S)-2,3-epoxy-3-phenylpropyl carbonate, at pH 6.4 and 25 degrees
      C, had a Vmax of 22 mumol min-1 mg-1 and a Km of 16 microM when assayed with a
      conventional spectrophotometer. When assayed under the same conditions with a 96
      well plate reader, the measured Vmax was 15 mumol min-1 mg-1 and the Km was 6.6
      microM. Some of these compounds were also found to be substrates for glutathione
      S-transferase, microsomal epoxide hydrolase, and porcine liver carboxylesterase.
      Indeed, 4-nitrophenyl 3,4-epoxy-3-phenylbutanoate was a 3.4-fold better substrate
      for porcine liver carboxylesterase than 4-nitrophenyl acetate when initial rates
      of hydrolysis were measured under the same conditions.

PMID- 8135351
TI  - Separation and analysis of 4'-epimeric UDP-sugars by ion-pair reversed-phase
      HPLC.
AB  - A simple and sensitive method for determination of 4'-epimeric UDP-sugars using
      ion-pair reversed-phase HPLC has been developed. The method presents advantages
      over existing ion-exchange HPLC procedures mainly concerning sensitivity and
      rapidity of analysis as well as efficiency and stability of the column. It is
      based on the ability of borate ions to react with cis-diols resulting in the
      formation of UDP-sugar-borate complexes with different charges. Good resolution
      and rapid separation (5-25 min) of all 4'-epimeric UDP-sugars tested was achieved
      with this method, was suitable for concentrations over 20 pmol. The applicability
      to biochemical analysis was demonstrated by the quantitative determination of the
      UDP-2-deoxyglucose and UDP-2-deoxygalactose formed in yeast cells upon incubation
      in the presence of 2-deoxygalactose.

PMID- 8135352
TI  - Cross-validation of cyanogen bromide-peptide ratios to measure the proportion of
      type II collagen in pepsin digests of equine articular cartilage, meniscus, and
      cartilage repair tissue.
AB  - Collagen type I and type II were purified from equine flexor tendon and articular
      cartilage, respectively. Equal amounts of these collagens were cleaved with
      cyanogen bromide, and 11 mixtures containing increasing proportions of type II
      collagen were separated in seven identical sodium dodecyl sulfate-polyacrylamide
      gels. The density of bands was measured in wet gels and the peak areas were used
      to form six ratios of peptide bands that had polynomial relationships with the
      known proportions of type I and type II collagen in the mixtures. Calibration
      curves for determining the proportion of type II collagen in the mixtures were
      constructed using ratios and combinations of ratios of peak areas. Cross
      validation was used to identify calibration curves with the smallest squared
      prediction error or squared average prediction error for all combinations of
      ratios. Ratios of peak areas of each one of the seven gels were treated, in turn,
      as the "unknown," and a prediction was carried out using these unknowns and the
      ratios from the other six gels. Two ratios had the smallest squared average
      prediction error and calibration curves were computed for these ratios with all
      seven gels. These curves were used to estimate the proportion of type II collagen
      in the pepsin-soluble and the pepsin-resistant fractions of articular cartilage
      inner and outer meniscus, and cartilage repair tissue. Cross-validation enabled
      selection of the cyanogen bromide-peptide ratios for calibration curves that
      resulted in the most accurate estimation of the proportion of type II collagen in
      pepsin digests of tissues.

PMID- 8135354
TI  - A method for high-performance sequence analysis using polyvinylidene difluoride
      membranes with a biphasic reaction column sequencer.
AB  - Methods have been developed for high-sensitivity sequence analysis of proteins
      electroblotted onto polyvinylidene difluoride (PVDF) membranes using a Hewlett
      Packard G1005A protein sequencer. This sequencer normally uses a biphasic
      (hydrophobic/hydrophilic) reaction column which was designed to accommodate
      loading and cleanup of samples from diverse solutions. However, the standard
      column, programs, and chemistry were not designed to accommodate PVDF, which has
      become a common sequencing support. In this study, a systematic evaluation of the
      suitability of this sequencer for analysis using PVDF bound samples was performed
      and included evaluation of: different wash and extraction solvents, multiple
      programming changes, two alternative formulations of coupling reagents, and the
      effect of direction for solvent and reagent deliveries. High-performance analysis
      of PVDF bound samples was achieved by: using a modified reaction column with an
      empty hydrophobic (top) half of the column module, program modifications for the
      reaction column and converter, substitution of ethyl acetate for the standard
      S2/3 extraction solvent and using prototype Version 2.0 formulations of the
      coupling reagents, R1 and R2. High-performance sequence analyses of experimental
      samples electroblotted from either 1D or 2D gels onto high-retention PVDF
      membranes were obtained with a 41-min cycle time, including experimental samples
      with initial coupling yields < 2 pmol. Routine sequencer performance was
      comparable to, or slightly better than, a conventional gas-phase sequencer which
      had been previously optimized by us for high-performance sequence analysis of
      electroblotted samples in the low pmol range.

PMID- 8135353
TI  - A continuous spectrophotometric method for the determination of monophenolase
      activity of tyrosinase using 3-methyl-2-benzothiazolinone hydrazone.
AB  - A continuous spectrophotometric method for the rapid determination of
      monophenolase activity of tyrosinase is described. This method is based on the
      coupling reaction between 3-methyl-2-benzothiazolinone hydrazone (MBTH) and the
      quinone products of the oxidation of various monophenols in the presence of
      tyrosinase. The chemical reaction between MBTH and o-quinone has been kinetically
      characterized, the lambda max and the molar absorptivity coefficients of the
      adducts have been calculated, and the stoichiometry of the reaction has been
      determined. The method is illustrated by measuring the enzymatic activity of
      mushroom tyrosinase during the hydroxylation of phenol and tyramine. The presence
      of MBTH in the reaction medium decreases the lag period present during the
      expression of monophenolase activity and the high epsilon values at 500-505 nm of
      the adducts make this method more sensitive than other continuous methods. The
      MBTH reaction in the presence of monophenols or o-diphenols has been optimized to
      stain tyrosinase obtained from different biological sources in electrophoresis
      gels.

PMID- 8135355
TI  - Comparison of glyceraldehyde-3-phosphate dehydrogenase and 28S-ribosomal RNA gene
      expression as RNA loading controls for northern blot analysis of cell lines of
      varying malignant potential.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been a gene of choice in
      Northern blot analyses as an internal RNA loading control. We have investigated
      the expression of GAPDH and 28S-ribosomal RNA (28S rRNA) genes in mouse 10T1/2
      cells and in a variety of tumorigenic and highly malignant metastatic cell lines
      derived from the 10T1/2 cell line. We observed that GAPDH mRNA levels varied
      markedly among the tumorigenic and highly malignant cell lines and were elevated
      in these cell lines when compared to the normal mouse 10T1/2 cells. In contrast,
      the levels of 28S rRNA did not significantly vary among the tumorigenic and
      highly malignant cell lines and were approximately at the same level as that
      found in the normal parental mouse 10T1/2 cell line. These observations indicate
      that much caution should be taken when using GAPDH gene expression as an RNA
      loading control for Northern blots. Based upon these observations, we recommend
      the use of 28S rRNA gene expression as a preferred RNA loading control for
      Northern blot analysis in which total RNA is used.

PMID- 8135356
TI  - A buffer exchange procedure giving enhanced resolution to polyacrylamide gels
      prerun for protein sequencing.

PMID- 8135357
TI  - Liquid scintillation counting of tritium-labeled neuropeptide in the subnanomole
      range: quantitative study of adsorption to vials.

PMID- 8135358
TI  - A rapid protein determination by modification of the Lowry procedure.

PMID- 8135359
TI  - T7 DNA polymerase requires unusual reaction conditions for blunt-ending activity.

PMID- 8135360
TI  - Direct cloning of polymerase chain reaction products in an XcmI T-vector.

PMID- 8135361
TI  - A device to facilitate the manual manipulation of arrayed libraries.

PMID- 8135362
TI  - Enhanced protein blotting from PhastGel media to membranes by irradiation of low
      intensity ultrasound.
AB  - A novel approach to protein blotting based on application of ultrasound is
      proposed. Three minutes of ultrasound exposure (1 MHz, 2.5 W/cm2) was sufficient
      for a very clear transfer of proteins from a polyacrylamide gel (PhastGel) to
      nitrocellulose or nylon 66 Biotrans membranes. The proteins evaluated were
      prestained sodium dodecyl sulfate-polyacrylamide gel electrophoresis standards
      (18,500-106,000 Da) and 14C-labeled Rainbow protein molecular weight markers
      (14,300-200,000 Da). In control experiments, which were performed following
      similar procedures without turning the ultrasonic generator on, no protein
      blotting could be seen. For comparable blotting results, 30 min for
      electroelution or 240 min for elution by convection blotting was required.

PMID- 8135363
TI  - Estimation of the folding/unfolding energetics of marginally stable proteins
      using differential scanning calorimetry.
AB  - We demonstrate a method for obtaining accurate estimates of the thermodynamic
      parameter values characteristic of a two-state folding/unfolding transition under
      conditions in which the onset of cold denaturation prevents the native state from
      being fully populated at any temperature. This situation occurs for proteins
      exhibiting low thermal stability, which may be intrinsic, the result of amino
      acid substitution, or the consequence of protein-solvent interactions (e.g.,
      extremes of pH, the presence of denaturants, extremes of ionic strength).
      Conventional analysis of calorimetric scans obtained under such conditions yields
      erroneous values for the enthalpy, entropy, and heat capacity changes
      characteristic of the folding/unfolding transition of the protein. This paper
      describes for the first time the weighted average enthalpy function. In contrast
      to the van't Hoff and calorimetric enthalpies, the weighted average enthalpy
      yields thermodynamic parameter values which differ by less than 5% form the true
      value, even for situations in which the population of molecules in the native
      state at the start of the transition is half of the total.

PMID- 8135364
TI  - Assay of tubulin acetyltransferase activity in subcellular tissue fractions.
AB  - An assay for alpha-tubulin acetyltransferase (TAT) activity based on affinity
      isolation of labeled acetylated alpha-tubulin was developed for use with crude
      subcellular fractions. Microtubules were polymerized and immobilized on an anti
      alpha-tubulin-agarose and then incubated with the subcellular fraction and
      [3H]acetyl-coenzyme A (CoA). The labeled product was eluted from the antibody
      agarose and the tritiated acetate incorporation determined. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and immunoblot of the eluate verified
      the presence of acetyl-alpha-tubulin. Analysis of bovine retinal fractions showed
      the highest specific activity of tubulin acetyltransferase activity in the
      27,000g pellet fraction (P2) of retinal homogenates. This transferase activity
      was proportional to the concentration of microtubule protein immobilized under
      polymerizing conditions and had an apparent Km of 3 microM for acetyl-CoA. The
      activity was solubilized from the P2 pellet by a high ionic strength buffer. The
      properties of the retinal TAT determined by this assay are very similar to those
      reported for a more purified enzyme preparation from Chlamydomonas flagella using
      the conventional trichloroacetic acid precipitation assay and support the use of
      this method for samples in which high backgrounds prohibit use of the
      conventional assay.

PMID- 8135365
TI  - Separation of inner and outer membrane vesicles from Escherichia coli in self
      generating Percoll gradients.
AB  - A rapid and simple method for separating and isolating the inner and outer
      membranes of Escherichia coli is described. Membrane vesicles were prepared
      either by passing the bacteria through a French press or by conversion of the
      cells to spheroplasts by the lysozyme-EDTA treatment and disruption of the
      spheroplasts by sonication. The membrane vesicles were collected by
      ultracentrifugation and suspended in a Percoll-containing buffer. The membranes
      were separated by centrifugation of the membrane-Percoll mixture in a fixed angle
      rotor at 27,000gmax for 30 min in a preparative centrifuge. One low-density and
      one high-density band was obtained, corresponding to the inner and outer
      membranes, respectively. For the membranes prepared by French pressing 69 and
      3.3% of the total activity in the gradient of the inner membrane marker NADH
      oxidase was found in the low-density and the high-density bands, respectively.
      For the outer membrane marker 2-keto-3-deoxyoctonate (KDO), 69 and 7.3% of the
      total amount of KDO in the gradient was found in the high-density and the low
      density bands, respectively. For the membranes prepared by sonication of
      spheroplasts the same figures were 39 and 6.5% for NADH-oxidase and 52 and 9.0%
      for KDO. The total time of preparation of membrane vesicles, from harvesting the
      bacteria to the separation of the inner and outer membrane vesicles, is about 6
      h. A good separation of the inner and outer membranes was still obtained when
      samples corresponding to about 10 mg of membrane protein were added to a 33-ml
      gradient.

PMID- 8135366
TI  - Determination of michellamine B in biological fluids by high-performance liquid
      chromatography with fluorescence detection.
AB  - The National Cancer Institute is pursuing preclinical development of michellamine
      B (MB), a novel dimeric polyhydroxylated naphthalene-tetrahydroisoquinoline
      alkaloid isolated from Ancistrocladus abbreviatus, as an anti-human
      immunodeficiency virus (HIV) agent. MB protects human lymphoid cells from the
      cytopathic effects of both HIV-1 and HIV-2 in vitro. A specific, sensitive, and
      convenient method for assaying the compound in biological fluids has been
      developed. Samples were prepared for analysis by initial treatment with dilute
      trichloroacetic acid followed by thorough mixing with a solution of the internal
      standard (alpha-naphthoflavone) in acetonitrile to denature macromolecules. The
      supernatant afforded by centrifugation, upon dilution with the aqueous component
      of the liquid chromatographic eluent, was loaded onto a 4-microns Nova-Pak phenyl
      column (3.9 mm x 15 cm). Chromatography was performed at ambient temperature
      using an isocratic mobile phase composed of 10 mM octyl sodium sulfate and 15
      microM tetrabutylammonium hydrogen sulfate in acetonitrile/0.05 M ammonium
      formate buffer, pH 4.0 (46/54, v/v), at a flow rate of 0.6 ml/min. The intense
      native fluorescence of MB, which exhibited excitation and emission maxima in the
      mobile phase at 232 and 393 nm, respectively, provided a highly sensitive and
      selective means of detection. Mean values of the retention times for the drug and
      internal standard determined over 11 months were 10.71 +/- 0.53 and 13.14 +/-
      0.52 min, respectively (SD, n = 52). Employing a sample volume of 50 microliters,
      the lowest concentration of MB included in the standard curves of mouse, dog, and
      human plasma, 10 ng/ml (11.4 nM), was quantified with coefficients of variation
      less than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135367
TI  - Quantitation of cysteine residues alkylated with 3-bromopropylamine by amino acid
      analysis.
AB  - A new versatile reagent, 3-bromopropylamine, for the quantitative analysis of
      cysteine residues in proteins and peptides is reported. When added to amino acid
      standards, the 3-bromopropylamine derivative of cysteine, S-3
      aminopropylcysteine, elutes in a unique position on four different amino acid
      analysis systems without modification to their standard gradients. Optimized
      conditions for the complete alkylation of cysteines in proteins with 3
      bromopropylamine are described. The S-3-aminopropylcysteine is stable to standard
      acid hydrolysis conditions used for amino acid analysis. Cysteine values are
      within 10% of the predicted value in the amino acid analysis of acid hydrolysates
      of known proteins based on quantitation with S-3-aminopropylcysteine. No evidence
      of alkylation of other amino acids by 3-bromopropylamine is apparent from the
      amino acid analysis of proteins alkylated under the optimal conditions. These
      results expand the application of 3-bromopropylamine to include quantitation of
      cysteine by amino acid analysis as well as the previously reported identification
      of cysteines by protein sequencing.

PMID- 8135368
TI  - A study of protein secondary structure by Fourier transform
      infrared/photoacoustic spectroscopy and its application for recombinant proteins.
AB  - FT-IR/PAS (Fourier transform infrared/photoacoustic spectroscopy) was used to
      evaluate the secondary structure of proteins. Four well-studied proteins,
      concanavalin A, hemoglobin, lysozyme, and trypsin, which have different
      distributions of secondary structures, were used for assignments of the infrared
      bands and evaluating the accuracy of FT-IR/PAS methods. Secondary structure
      contents estimated from FT-IR/PAS and other physical methods (e.g., X-ray
      diffraction, CD, and traditional FT-IR) show good agreement. In addition, the
      secondary structure can be evaluated with as little as 0.5 micrograms of protein
      (concanavalin A), suggesting that FT-IR/PAS is a sensitive and useful technique
      that could be applied to studies of the folding of recombinant and mutant
      proteins where only small amounts of material are available. Recombinant
      phosphorylase kinase gamma 1-300 subunit expressed in Escherichia coli was found
      in the inclusion bodies. We found that renatured phosphorylase kinase gamma 1-300
      subunit has two kinase forms: one has a 10-fold higher activity than the other
      one. Both fractions, however, are the same as judged from sodium dodecylsulfate
      polyacrylamide gel electrophoresis. Differences in conformation were demonstrated
      by using the FT-IR/PAS method, which showed that the low-activity form has more
      beta-sheet structure than the form with high activity. Analysis of these kinase
      forms by CD confirms the interpretation made by the FT-IR/PAS method.

PMID- 8135369
TI  - Polystyrene reverse-phase ion-pair chromatography of chimeric ribozymes.
AB  - The use of a reverse-phase polystyrene resin for ion-pair HPLC purification of
      large amounts of synthetic chimeric DNA-RNA oligomers that is faster and more
      reliable than previously used techniques has been developed. The preparation of
      synthetic oligomers containing RNA requires the use of tetrabutylammonium
      fluoride in the final step, the cleavage of the tert-butyl-dimethyl silyl
      protecting group from the ribonucleotides. Cleavage is accompanied by the
      serendipitous formation of ion pairs between tetrabutylammonium cations and the
      oligomer phosphates. The formation of these ion pairs retards the elution of the
      oligomer during HPLC, which allows rapid removal of excess tetrabutylammonium
      fluoride and the concomitant purification of chimeric ribozymes. This technique
      is based on a correlation between the length of ion-paired oligomers and their
      retardation during HPLC. The advantages of reverse-phase ion-pair HPLC on
      polystyrene resin for the fast purification of oligoribonucleotides are discussed
      and illustrated through the examples of synthesized chimeric ribozymes.

PMID- 8135370
TI  - Discovery and analysis of a series of C2-symmetric HIV-1 proteinase inhibitors
      derived from penicillin.
AB  - In order to identify a suitable peptide substrate for human immunodeficiency
      virus-1 (HIV-1) proteinase, a range of peptides from various cleavage sites
      within the gag-pol polyprotein were assayed by HPLC for specific cleavage. The
      peptide with the optimal combination of favorable kinetics and good solubility
      was based on the N-terminus cleavage site of HIV-1 proteinase (KQGTVSFNF*PQIT).
      The HPLC assay, using the above peptide, was developed into a rapid isocratic
      method in order to analyze inhibition kinetics. An assay suitable for high
      throughput screening was developed using a radioactively labeled peptide with the
      same sequence, coupled to a solid phase. Using this assay, a C2-symmetric HIV-1
      proteinase inhibitor derived from penicillin was discovered during random
      screening of a compound library. A chemical synthesis program developed this
      structure into a series of potent inhibitors. The lead structures were highly
      selective for HIV-1 proteinase with good antiviral activity in vitro against HIV
      and no cytotoxicity. The HPLC assay was used to demonstrate that these compounds
      are competitive tight-binding inhibitors of HIV-1 proteinase.

PMID- 8135371
TI  - Determination of multidrug resistance levels in cultured mammalian cells using
      ornithine decarboxylase activity.
AB  - We describe an ornithine decarboxylase (ODC) activity-based assay for the
      quantitation of multidrug resistance (MDR) and its reversal by MDR modulators in
      cultured mammalian cells. ODC catalyzes the first and rate-limiting step in
      polyamine biosynthesis. The activity of this enzyme rises rapidly after growth
      initiation, such as after addition of serum-containing medium to quiescent
      mammalian cells. This increase in enzyme activity is prevented when growth is
      arrested, such as after treatment with cytotoxic drugs. In this assay cultures of
      drug-sensitive animal and human carcinoma cells as well as their MDR sublines
      were exposed to various concentrations of different cytotoxic agents for 6-48 h.
      A dose-dependent decrease in ODC activity was obtained with a variety of
      chemotherapeutic agents including anthracyclines, vinca alkaloids,
      epipodophyllotoxins, actinomycin D, antifolates, and cisplatinum. Anticancer drug
      resistance levels were calculated as the 50% inhibitory concentration of ODC
      activity obtained with drug-resistant cells divided by that obtained with
      sensitive cells. These cytotoxicity determinations correlated favorably with
      those obtained by the well-established colony formation assay. The ODC assay also
      proved useful in the assessment of MDR reversal with modulators of the MDR
      phenotype. Therefore, these studies show that the ODC assay could be useful for
      the reliable determination of drug resistance levels in cultured mammalian cells
      and for the assessment of drug resistance reversal by various modulators of the
      MDR phenotype.

PMID- 8135372
TI  - Characterization of human breast biopsy specimens with near-IR Raman
      spectroscopy.
AB  - Breast biopsy samples were examined with Raman spectroscopy with laser
      wavelengths ranging from 406 to 830 nm. A combination of a single-stage
      spectrograph, band reject filter, and CCD detector permitted low laser powers and
      minimal risk of sample radiation damage. Spectra of formalin-fixed human tissue
      revealed Raman features for lipids and carotenoids. The best defined lipid
      features were observed for 782- and 830-nm laser excitation, while carotenoid
      features were strongest in the 488-515-nm range due to resonance enhancement.
      Comparison of the spectra with those of fatty acid esters revealed that the major
      lipid component is a derivative of oleic acid. Lipid and carotenoid Raman bands
      were superimposed on a luminescent background which was less prominent at longer
      laser wavelengths. A compact, portable, diode laser spectrometer was tested in a
      clinical setting with fiber optic sampling. The results indicate that substantial
      biochemical information is available from near-IR Raman spectroscopy and the
      technique may have clinical applications.

PMID- 8135373
TI  - Influence of pH on retention and selectivity in micellar liquid chromatography:
      consequences of micellar-induced shifts of ionization constants.
AB  - The retention and selectivity of ionizable solutes in the two-surfactant-mediated
      reversed-phase LC techniques (micellar and ion pair) are compared through the use
      of a general retention equation for mono- and zwitterionic solutes. In RPLC with
      different mobile-phase modifiers (organic solvents, surfactants), the influence
      of pH can be quantitatively described by one general equation. The existing
      theory for the secondary chemical equilibria has been applied to compare
      selectivity effects in micellar and ion-pair chromatography. In order to predict
      the influence of different mobile-phase compositions on the selectivity of
      ionizable compounds, one should determine how a mobile-phase parameter influences
      the ionization equilibria (i.e., selective shifts of pKa) and self-selectivity
      (defined as the ratio of retention factors of the acid/conjugate base). For
      example, the first ionization constants of amino acids and peptides in aqueous
      mobile phase are between pH 2.3 and 3.4. Consequently, the pH required to
      maximize the retention of these solutes by ion suppression is less than the
      operational pH range of silica-based columns. In addition, since the pKa1 values
      of these solutes are similar, adjustment of pH has little effect on separation
      selectivity. In contrast, ion-pairing and micellar mobile phases with SDS
      surfactant increase the magnitude and range of the ionization constants. These
      trends are more pronounced with micellar mobile phase. The displacement of solute
      ionization constants to higher PH with micellar mobile phase allows the maximal,
      limiting, retention of zwitterionic solutes to be observed within the pH limits
      of silica-based columns.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135374
TI  - Protein sorting by high performance liquid chromatography. 2. Separation of
      isophosphorylates of recombinant human DNase I on a polyethylenimine column.
AB  - Anion exchange HPLC with a polyethylenimine (PEI) column separates recombinant
      human deoxyribonuclease I (rhDNase) glycoforms according to the extent and
      positions of phosphorylation of mannose residues in N-linked oligosaccharides.
      The separation provides a selectivity unavailable by anion exchange HPLC with
      other columns or by isoelectric focusing gel electrophoresis and can be used to
      quantify the phosphate content of preparations of rhDNase. Tryptic mapping of
      fractions collected from the column and treated with alkaline phosphatase was
      used to identify the sites of phosphorylation. Unnatural forms of rhDNase,
      bearing oligosaccharide structures at only one of the two sites of glycosylation,
      were prepared by cleaving the phosphate-containing high mannose and hybrid
      structures from the purified isophosphorylates fractionated on the PEI column.
      The separation of rhDNase isophosphorylates on the PEI column mimics the relative
      affinities for the mannose 6-phosphate receptor that traffics acid hydrolases to
      lysosomes and provides a useful example of protein sorting by biomimetic
      interaction chromatography.

PMID- 8135375
TI  - A novel immunosensor for herpes viruses.
AB  - We have developed a reusable piezoelectric immunosensor for the detection of the
      following human herpes viruses: herpes simplex viruses types 1 and 2, varicella
      zoster virus, Epstein-Barr virus, and cytomegalovirus. Synthetic peptides,
      representing different surface antigens of the five viruses, were used to
      generate virus-specific monoclonal antibodies. Apply an antibody layer via
      protein A immobilization onto a 10-MHz AT-cut crystal resulted in 5 x 10(4)-1 x
      10(9) viruses on the electrode surface in a linear frequency change and a long
      term stability of 8 weeks when the modified crystal was stored dry over silica
      gel blue at room temperature. Under these conditions, the coated crystal can be
      used 18 times without detectable loss of activity.

PMID- 8135376
TI  - Spatial and temporal imaging of gas phase protein and DNA produced by matrix
      assisted laser desorption.
AB  - The sensitivity of a transient imaging technique based on laser-excited
      fluorescence is shown to be within the levels required for studying matrix
      assisted laser-desorption (MALD) of large biomolecules. Results show that film
      morphology, particularly film thickness, has a major influence on plume dynamics.
      Fluorescent labeling of protein and of DNA is used to allow imaging in UV-MALD
      generated plumes. Evidence that intact molecules are monitored is provided. Dye
      molecules, proteins and DNAs were found to behave very differently in the
      vaporization process. The spatial and temporal distributions are important for
      the design of secondary ionization schemes to enhance ion yields, for the
      optimization of ion collection, and for maximizing resolution in time-of-flight
      mass spectrometers.

PMID- 8135377
TI  - Ultrasonically assisted electrospray ionization for LC/MS determination of
      nucleosides from a transfer RNA digest.
AB  - The use of an ultrasonic nebulizer to assist electrospray ionization mass
      spectrometry (ESI-MS) has been described and demonstrated with the analysis of a
      transfer RNA digest by microcolumn LC. The restricted range of mobile-phase
      compositions amenable to the electrospray process has traditionally placed a
      severe limitation on the types of LC applications that can be used with ESI-MS.
      For this reason, an ultrasonic nebulizer configured for LC has been developed
      that can generate the fine dispersion of liquid required for ESI-MS from any type
      of mobile phase. In the case presented here, a transfer RNA was enzymatically
      digested into its substituent nucleosides, which were then analyzed by
      microcolumn LC. The required mobile-phase gradient (beginning at 5% methanol)
      falls outside the solvent range that can be used with conventional electrospray.
      The ultrasonic nebulizer, however, resolves this problem. The fundamental
      behavior of the four most common nucleosides (cytidine, adenosine, guanosine,
      uridine) was studied, and conclusions concerning the effects of solution
      chemistry were drawn. Specifically, signal from the H+ adducts of these species
      seems to be strongly dependent on the pKa value. Also, effects from several
      source operating variables were examined. These included capillary exit voltage,
      drying and focusing gases, and nebulizer frequency. Performance was found to be
      consistent over a wide range (0-100% methanol) of mobile-phase compositions. The
      limit of detection for adenosine injected onto a microcolumn was found to be 100
      amol. Finally, nucleosides from as little as 150 fmol of RNA (amount prior to
      digestion) could be detected.

PMID- 8135378
TI  - High-resolution tandem mass spectrometry of carbonic anhydrase.
AB  - Electrospray ionization of carbonic anhydrase with ion dissociation yields a mass
      spectrum from which the masses of > 100 isotopic clusters are determined
      accurately, with the number of charges assigned directly from resolved isotopic
      peaks. Of these clusters, 80% correspond to fragmentation at or near the amino
      acid proline. The masses of combinations of two, three, and four of these
      clusters sum to the molecular mass with 0.1-Da accuracy, while further fragment
      ion dissociation provides additional sequence information. The capability of this
      methodology to detect sequence variations is illustrated with an isozyme having a
      single amino acid replacement.

PMID- 8135379
TI  - Pharmacy acquisition costs: responsible choices versus overutilization of costly
      pharmaceuticals.

PMID- 8135380
TI  - Significance of electrocardiographic ST elevation during coronary artery bypass
      surgery.
AB  - The aim of this study was to determine the significance of new
      electrocardiographic (ECG) ST elevation during coronary artery bypass surgery.
      Multilead ECGs were recorded intraoperatively approximately every 3 min on 105
      patients. Cases of new ST elevation were divided into ischemic and those
      considered to be due to nonischemic causes such as cooling during cardiopulmonary
      bypass (CPB), defibrillation, new cardiac conduction abnormalities, and
      pericarditis. The myocardial fraction of creatine kinase (CK-MB) > or = 25 IU/L
      was considered to be indicative of myocardial injury. Both patients who had
      ischemic ST elevation prior to CPB and all seven patients who had ST elevation in
      temporal association with the administration of protamine had peak CK-MB > or =
      25 IU/L. One patient with peak CK-MB > or = 25 IU/L did not have ST elevation and
      was considered to have injury during CPB. Two of these ten patients had Q wave
      myocardial infarctions (MIs). For the detection of patients with peak CK-MB > or
      = 25 IU/L, the sensitivity of ischemic ST elevation was 90% and the specificity
      was 100%. A history of MI prior to surgery and a history of Type I diabetes were
      associated with peak CK-MB > or = 25 IU/L (P < 0.05).

PMID- 8135381
TI  - Nasal colonization with methicillin-resistant Staphylococcus aureus on admission
      to the surgical intensive care unit increases the risk of infection.
AB  - We prospectively studied the relationship of perioperative methicillin-resistant
      Staphylococcus aureus (MRSA) nasal colonization and subsequent infection in
      surgical intensive care unit (SICU) patients. In addition, risk factors for MRSA
      nasal colonization were examined. All patients admitted to the 15-bed SICU
      between August 1991 and July 1992 had their anterior nares cultured. Cultures
      positive for S. aureus were subsequently placed on oxacillin-containing plates to
      screen for methicillin-resistance. Of 484 patients, 19 had MRSA nasal
      colonization (3.9%). There were five infections in the 19 patients with positive
      perioperative nasal cultures versus six infections in the remaining 465 patients
      (P < 0.0001). Immunoblot typing confirmed the concordance of colonizing and
      infecting strains. Prior exposure to the spinal cord injury center (P < 0.001)
      and prior antibiotic therapy (P < 0.003) were also significant multivariate risk
      factors for perioperative nasal colonization. Patients with perioperative MRSA
      nasal colonization are at significantly increased risk of subsequent
      postoperative MRSA infection.

PMID- 8135382
TI  - "Do not resuscitate" (DNR) orders in the perioperative period--a comparison of
      the perspectives of anesthesiologists, internists, and surgeons.
AB  - The purpose of this descriptive study is to compare and contrast the experience,
      perceptions, and opinions of practicing anesthesiologists, internists, and
      surgeons regarding "do not resuscitate" (DNR) orders in the perioperative period.
      A questionnaire was mailed to 600 internists and 600 surgeons. Responses from
      these two groups were analyzed and compared with the results of a previously
      reported survey of 420 anesthesiologists. One hundred ninety-two of 570 (34%) and
      199/584 (34%) acknowledged responses were received from internists and surgeons,
      respectively. Anesthesiologists (114/190; 60%) were more likely than internists
      (61/182; 34%) or surgeons (71/194; 37%) to assume DNR suspension in the
      perioperative period and were less likely than their colleagues to discuss with
      the patient the implications of their DNR order during anesthesia and surgery.
      This assumption of DNR suspension by anesthesiologists was underestimated by both
      surgeons and internists. Anesthesiologists and surgeons were more similar than
      internists in their manner of utilization of resuscitative measures in the
      setting of a cardiopulmonary arrest. All groups were more likely to require DNR
      suspension for elective than for palliative cases. The majority of all groups
      concurred that physician responsibility for defining DNR status in the
      perioperative period should be shared by the anesthesiologist, surgeon, and
      primary care physician and not prescribed by hospital policy. The manner in which
      a DNR order is perceived in the perioperative period varies considerably among
      specialties and warrants further discussion among these groups.

PMID- 8135383
TI  - The laryngeal mask airway in pediatric patients: factors affecting ease of use
      during insertion and emergence.
AB  - Use of the laryngeal mask airway (LMA) permits the maintenance of a patent airway
      with successful insertion rates of the LMA on the first attempt varying between
      67%-92% in children. The recommended insertion technique involves deflation of
      the mask using a syringe, and application of a lubricant jelly. In a randomized
      study of 122 children, we compared the time to complete LMA insertion, the number
      of attempts before successful placement, and the occurrence of laryngospasm and
      Spo2 < 90% during insertion using the standard deflated method and an alternative
      method of insertion with the LMA cuff partially inflated. Independently, the
      children were randomly assigned to have K-Y sterile lubricating jelly or 2%
      lidocaine topical solution applied to the back of the mask. The occurrence of
      coughing, laryngospasm, and vomiting during emergence were recorded. Insertion of
      the LMA partially inflated required significantly less time (16 vs 23 s, P <
      0.05), and was associated with a higher success rate on first attempts (85.5% vs
      96.7%, P < 0.05). In those who did not receive morphine, 2% lidocaine topical
      solution decreased the incidence of coughing on emergence (10.3% vs 36.4%). The
      ease of insertion of the LMA in children was improved by partial inflation of the
      cuff and in addition, 2% lidocaine topical solution was as beneficial as morphine
      in reducing coughing on emergence.

PMID- 8135384
TI  - Clonidine in pediatric caudal anesthesia.
AB  - Extradural clonidine produces analgesia in adults. To assess its efficacy in
      children, we randomized 45 pediatric patients aged 1-7 yr presenting for a
      subumbilical surgery into three groups of 15 each. After halothane and N2O/O2
      induction, and with a double-blind protocol, caudal anesthesia was performed with
      1 mL/kg of 0.25% bupivacaine. Epinephrine 1/200,000 was added in one group (EG),
      1 microgram/kg of clonidine in another group (CG), and no additional medication
      in the last group (BG). Postoperative analgesia was evaluated using the Broadman
      "objective pain/discomfort scale" (OPS) at 1-h intervals until the first
      analgesic administration. There were no differences among the groups in age,
      weight, duration of surgery, baseline systolic arterial pressure, and heart rate.
      The mean (+/- SD) duration of analgesia was longer in the CG (987 +/- 573 min)
      than in the EG (377 +/- 341 min) and BG (460 +/- 439 min); P < 0.01. The maximal
      OPS scores were lower in the CG than in the EG and BG (2.3 +/- 1.6 vs 3.4 +/- 1.4
      and 3.4 +/- 1.8, respectively; P < 0.05). More patients in the CG (n = 7) than in
      the EG (n = 1) and BG (n = 2) required no postoperative analgesia; P < 0.05. No
      differences were found among the groups for the minimal respiratory rate and
      minimal Spo2 values in the postoperative phase, and there were no differences
      among the groups for heart rate and systolic arterial pressure during the 3 h
      after caudal anesthesia. We conclude that the duration of postoperative analgesia
      with caudal bupivacaine was significantly increased by the addition of 1
      microgram/kg of clonidine.

PMID- 8135385
TI  - Comparison of spinal and epidural anesthesia for patients younger than 50 years
      of age.
AB  - To evaluate the respective clinical value of spinal anesthesia with 24-gauge
      Sprotte needles and epidural anesthesia for younger subjects, 202 patients
      younger than 50 yr were assigned randomly to undergo one of these two techniques
      for orthopedic, vascular, urologic, or plastic surgery. Failed blocks occurred in
      5% in each group. Spinal anesthesia resulted in significantly less time to
      achieve sufficient spread of block; a significantly lower incidence of incomplete
      sensory block at level L5/S1, incomplete motor block, and pain during surgery;
      and a significantly lower incidence of postlumbar puncture backache (11% vs 30%
      after epidural anesthesia). The incidence of postdural puncture headache (PDPH)
      in the spinal and epidural groups was 7% and 4%, respectively (P = not
      significant), and patient satisfaction was 97% and 93% (P = not significant). Our
      results demonstrate the effectiveness of both techniques in younger patients, but
      show that the spinal technique is associated with fewer limitations, suggesting
      that factors other than PDPH should be considered when choosing between these two
      techniques.

PMID- 8135386
TI  - Splanchnic release of potassium after hemorrhage and succinylcholine in rabbits.
AB  - Recent clinical reports document that hyperkalemia may occur after
      succinylcholine (SCh) administration in hemorrhagic, acidotic humans.
      Hemorrhagic, acidotic rabbits are a useful model for study of this phenomenon
      because of profound hyperkalemia after SCh. To determine the etiology of this
      hyperkalemia, we anesthetized rabbits (n = 5, Group H) with halothane/N2O, and
      after endotracheal intubation, placed catheters in the femoral artery, femoral
      vein (FV), and inferior vena cava (IVC), the latter at or above the hepatic
      veins. After measurement of baseline K+ (from each catheter) and arterial blood
      gases, approximately 30 mL/kg of blood was withdrawn, and the animal was allowed
      to become acidotic until pH approximately 7.00-7.10. Plasma K+ was determined
      again, and SCh 1 mg/kg administered intravenously. Blood from each catheter was
      withdrawn for K+ analysis at 1, 3, 5, and 7 min after SCh. Control rabbits (Group
      C, n = 5) were similarly anesthetized and catheterized but were not hemorrhaged.
      Arterial blood gas and K+ analyses were performed before and after SCh 1 mg/kg,
      similar to Group H. In Group H, arterial K+ concentration increased after
      hemorrhage (3.2 +/- 0.3 mmol/L to 6.4 +/- 2.0 mmol/L, P < 0.05). SCh caused a
      further increase, peaking at 8.3 +/- 1.5 mmol/L at 7 min (P < 0.05). In Group H
      the IVC-FV K+ difference was 1.6 +/- 1.9 mmol/L, 1.5 +/- 2.1 mmol/L, 0.9 +/- 1.6
      mmol/L and 1.6 +/- 1.4 mmol/L, respectively, for the 1-, 3-, 5-, and 7-min
      periods after SCh.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135388
TI  - Visual estimation of train-of-four responses at the orbicularis oculi and
      posttetanic count at the adductor pollicis during intense neuromuscular block.
AB  - Posttetanic count (PTC) predicts the time to return of train-of-four (TOF)
      responses at the adductor pollicis (AP) muscle. The duration of neuromuscular
      block at the orbicularis oculi (OO) is shorter than at the AP. The aim of this
      study was to assess whether TOF at the OO can predict, as accurately as PTC does,
      the time to return of TOF at the AP. Twenty patients, ASA grade I or II, were
      studied. Anesthesia was induced with propofol, 2-3 mg/kg, intravenously (IV), and
      fentanyl, 2-3 micrograms/kg IV, and maintained with a propofol infusion. Ulnar
      and facial nerves were stimulated simultaneously with TOF every 20 s. PTC at the
      AP was repeated every 5 min. The number of twitches after PTC was estimated by
      feeling the responses at the thumb. TOF responses at the OO were monitored
      visually. TOF responses at the AP were recorded using a force transducer.
      Patients were assigned randomly to receive either atracurium, 0.5 mg/kg (n = 10),
      or pancuronium, 0.1 mg/kg (n = 10). Times from injection to the first response to
      PTC (PTC1), to the reappearance of the first response of TOF at the OO (T1OO),
      and to the reappearance of the first response of TOF at the AP (T1AP) were
      recorded. After pancuronium and atracurium, PTC1 and T1OO recovered before T1AP
      (P < 0.001). In all patients, PTC1 recovered earlier than T1OO (P <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135387
TI  - Quantifying the interaction of rocuronium (Org 9426) with etomidate, fentanyl,
      midazolam, propofol, thiopental, and isoflurane using closed-loop feedback
      control of rocuronium infusion.
AB  - The present study was designed to evaluate the interactions of rocuronium with
      etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed
      loop feedback control of infusion of rocuronium. Sixty patients were randomly
      assigned to one of six sequences where anesthesia was maintained with etomidate,
      fentanyl, midazolam, propofol, or thiopental and nitrous oxide, or with
      isoflurane and nitrous oxide. The possible interaction of rocuronium with the
      anesthetics was quantified by determining the asymptotic steady-state rate of
      infusion (Iss) of rocuronium necessary to produce a constant 90% neuromuscular
      block. This was accomplished by applying nonlinear curve fitting to data on the
      cumulative dose requirement during the initial 90-min period after bolus
      administration of rocuronium. Patient characteristics and controller performance,
      i.e., the ability of the controller to maintain the neuromuscular block constant
      at the set-point, did not differ significantly between the groups. Iss values
      calculated per lean body mass were 0.64 +/- 0.22, 0.60 +/- 0.15, 0.61 +/- 0.21,
      0.67 +/- 0.31, 0.63 +/- 0.15, and 0.39 +/- 0.17 mg.kg-1.h-1 in the etomidate,
      fentanyl, midazolam, propofol, thiopental, and isoflurane groups, respectively.
      The isoflurane group had a lower steady-state rate of infusion of rocuronium than
      the other five groups (P < 0.05). Compared to intravenous anesthetics, etomidate,
      fentanyl, midazolam, propofol, or thiopental, isoflurane reduced the infusion
      requirement of rocuronium by 35%-40%.

PMID- 8135389
TI  - Efficacy of methylnaltrexone versus naloxone for reversal of morphine-induced
      depression of hypoxic ventilatory response.
AB  - Methylnaltrexone (MNTX) is a quaternary derivative of naltrexone. It does not
      cross the blood-brain barrier and, thus, it reverses peripherally mediated
      effects of morphine without blocking its centrally located analgesic effects. The
      effects of MNTX on morphine-induced depression of hypoxic ventilatory response
      are unknown. We evaluated the efficacy of MNTX, compared with naloxone, in
      reversing this effect. On three sessions separated by a week, 10 healthy male
      volunteers received morphine, 0.125 mg/kg, as a bolus at 20 min after completing
      a control hypoxic ventilatory challenge. At 60 min, naloxone, 5 micrograms/kg,
      MNTX, 0.3 mg/kg, or placebo was administered in a randomized double-blind order.
      Four isocapnic hypoxic ventilatory challenges were conducted: 0 min (control), 40
      min (postmorphine), and 80 and 120 min (postreversal) and the hypoxic respiratory
      responses were recorded. Morphine administration was associated with a
      significant depression in hypoxic responses: The slope of the response
      (L/min/Spo2) and the predicted ventilation at 80% O2 saturation (VE80) (L/min)
      decreased significantly in the three sessions (P < 0.05). Naloxone injection
      reversed the respiratory depression at 80 min (85% of the control value of the
      slope and 89% of VE80), whereas MNTX and placebo did not. At 120 min, the slope
      (69%) and VE80 (80%) after naloxone administration were not significantly
      different from control. MNTX slope (69%) was not statistically different from the
      control, whereas VE80 (70%) was still depressed (P < 0.05). Placebo slope and
      VE80, at 120 min, remained lower than the control (P < 0.05). These data show
      that MNTX is not as effective as naloxone for reversal of morphine-mediated
      depression of respiration during acute hypoxia.

PMID- 8135390
TI  - The effect of isoflurane or spinal anesthesia on indocyanine green disappearance
      rate in the elderly.
AB  - This study was designed to measure the disappearance rate of indocyanine green
      (ICG) as an indicator of hepatic blood flow in elderly patients undergoing
      internal fixation of fractured neck of femur. All patients were aged 60-90 yr and
      were randomized to receive either spinal (n = 10) or isoflurane (n = 10)
      anesthesia. In both groups systolic arterial blood pressure was maintained within
      15% of resting levels by administration of fluids intravenously without
      vasoactive drugs. Patients were excluded if they required vasopressors to
      maintain arterial blood pressure. ICG disappearance rate was calculated using a
      single bolus technique before induction of anesthesia, and at 30, 60, and 120 min
      after induction of anesthesia. Sixteen patients completed the study. There were
      no statistically significant changes in ICG disappearance rate in either group at
      any time during the study, indicating that hepatic blood flow is not
      significantly altered by either spinal or isoflurane anesthesia provided that
      arterial blood pressure is maintained.

PMID- 8135391
TI  - Midazolam produces vasodilation by mixed endothelium-dependent and -independent
      mechanisms.
AB  - Aortic rings were obtained from rat thoracic aorta and studied in vitro with and
      without functionally intact endothelium to determine whether "the mechanism"
      requires endothelium [or endothelium-derived relaxing factor (EDRF)]. In aortic
      rings precontracted with either phenylephrine (PE, 3 x 10(-8)-3 x 10(-7) mol/L)
      or KCl (40 mmol/L), midazolam produced concentration-dependent relaxation, with
      and without endothelium. Rings without endothelium demonstrated significantly
      less relaxation than those with endothelium regardless of whether they were
      precontracted with PE or KCl. With intact endothelium, midazolam produced greater
      relaxation in PE-contracted aortic rings than in KCl-contracted aortic rings; the
      midazolam concentration producing 50% relaxation from the contracted state (RC50)
      was 8.8 +/- 3.6 x 10(-7) mol/L for PE-contracted rings and 3.3 +/- 1.1 x 10(-6)
      mol/L for KCl-contracted rings (P < 0.05). In aortic rings with intact
      endothelium pretreated with NG-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L), an
      inhibitor of nitric oxide (NO) synthesis, midazolam produced relaxation of
      similar magnitude to that seen in the denuded aortic rings except at the highest
      concentration (1 x 10(-5) mol/L). Pretreatment with the cyclooxygenase inhibitor,
      indomethacin (2.5 x 10(-5) mol/L), did not change the midazolam-induced
      relaxation in rings with intact endothelium as compared to untreated control
      aortic rings. In contrast to the intact endothelium state, when endothelium was
      removed, midazolam produced greater relaxation in the KCl-contracted aortic rings
      than in PE-contracted rings (RC50, 1.2 +/- 0.3 x 10(-5) mol/L vs 2.3 +/- 0.4 x
      10(-5) mol/L, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135392
TI  - Structure-selective anesthetic action of steroids: anesthetic potency and effects
      on lipid and protein.
AB  - Alphaxalone was a clinically used steroid anesthetic. Its analog delta 16
      alphaxalone is nonanesthetic. The only difference between the two is the presence
      of a double bond at the hydrophobic end of the delta 16-alphaxalone molecule.
      This study determined the anesthetic potency of alphaxalone and delta 16
      alphaxalone in goldfish and compared it with their effects on
      dipalmitoylphosphatidylcholine (DPPC) membranes and an alpha-helix polypeptide,
      poly(L-lysine). The goldfish EC50 values were: alphaxalone 5 mumol/L and delta 16
      alphaxalone 80 mumol/L. Because these steroids are insoluble to water, the bulk
      of the steroid in water is absorbed by the fish. Larger containers hold more
      steroids than smaller containers at the same steroid concentrations. Then, EC50
      values vary according to the size of the container. By assuming that the total
      amount of steroids in the container is distributed into the fish, the EC50 values
      expressed by the concentration in the fish body become 1.9 mmol/L for
      alphaxalone, and 30.5 mmol/L for delta 16-alphaxalone. A monoamino acid peptide,
      poly(L-lysine), can be formed into random-coil, alpha-helix, or beta-sheet.
      Addition of 0.07 mmol/L alphaxalone to the alpha-helix poly(L-lysine) partially
      transformed it to a beta-sheet structure. An equivalent change was observed with
      3.0 mmol/L delta 16-alphaxalone. These values translate into 3.5 mmol/L for
      alphaxalone and 0.15 mol/L for delta 16-alphaxalone, when expressed by the
      concentration in the peptide. The change from alpha-helix to beta-sheet is
      accompanied by dehydration of the surface of poly(L-lysine). The steroids
      decreased the phase-transition temperature of DPPC membrane.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8135393
TI  - The effect of fentanyl and morphine on neurons in the dorsal raphe nucleus in the
      rat: an in vitro study.
AB  - The dorsal raphe (DR) nucleus is a system of nuclei lying in the midline of the
      lower brainstem constituting the largest collection of serotonin-containing
      neurons in the brain. The DR nucleus, which is under the influence of various
      synaptic inputs containing the excitatory amino acids (EAAs), serotonin and
      noradrenaline (NA), has been reported to be involved in the process of
      nociception. We studied the effects of fentanyl and morphine on the firing
      activity of neurons within the DR nucleus in the rat brain slice preparation in
      vitro using extracellular recording techniques. The decreased activity of DR
      neurons induced by these opioids was reversed upon application of naloxone. Since
      almost all neurons were silent, N-methyl-D-aspartate (NMDA) and noradrenaline
      were used to excite the DR neurons. Serotonin contained in the DR nucleus acts as
      a neuromodulator to enhance the excitatory effects of NMDA. All DR neurons were
      excited by NMDA, whereas 72% of the neurons were excited by NA. NA has a long
      lasting effect on the firing activity of the neurons, although the firing pattern
      was less regular than that induced by NMDA. Of the total number of the DR neurons
      excited by NMDA and/or NA, 71% were inhibited by fentanyl and 73% by morphine.
      The results support our hypothesis that these opioids inhibit the firing activity
      of DR neurons and, in turn, might alter nociception directly and/or indirectly by
      modifying the central serotonergic system.

PMID- 8135394
TI  - Diaphragmatic and abdominal muscle activity after endoscopic cholecystectomy.
AB  - We studied diaphragmatic and abdominal muscle activity immediately and 16 h after
      laparoscopic cholecystectomy (LAPC). Tidal volumes (VT), partitioning of VT
      between the rib cage and the abdomen, and esophageal, gastric, and
      transdiaphragmatic pressures were recorded for 5 min every 15 min up to 90 min
      after the end of anesthesia in 10 young patients submitted to an elective LAPC.
      All had chest radiographs in full inspiration and expiration as well as lung
      function tests (LFTs) before and 16 h after surgery. In 5 of the 10 patients,
      thoracoabdominal patterns of breathing were also measured before both LFTs. After
      LAPC, VT did not change. There was no significant shift from abdominal to
      thoracic respiration. No paradoxical respiration developed. Functional residual
      capacity (FRC) and residual volume (RV) remained normal. However, all measures of
      LFTs requiring maximum inspiratory effort decreased up to 20%. Tonic and phasic
      activity of the abdominal muscle appeared early in the recovery period and
      disappeared after 75 min. The diaphragm adjusted to this additional load so that
      VT remained constant. These results indicate that diaphragm function is intact
      during quiet breathing after LAPC, but slightly reduced when maximum effort is
      needed. However, this represents a net gain over the changes previously described
      after classic "open" cholecystectomy (OC).

PMID- 8135396
TI  - Current controversies in obstetric anesthesia.

PMID- 8135395
TI  - Facilitation of fiberoptic orotracheal intubation with a flexible tracheal tube.
AB  - Advancement of a tracheal tube (TT) over a flexible fiberoptic bronchoscope (FOB)
      is often impeded by obstruction at the arytenoid cartilage or epiglottis. We
      tested the hypothesis that the use of a flexible, spiral-wound TT, rather than
      the standard, preformed TT would facilitate tube passage into the trachea over
      the FOB. Forty patients scheduled to undergo general anesthesia with tracheal
      intubation were randomized to two groups. Then the trachea was intubated with a
      FOB, followed by passage of either a standard, preformed TT or a flexible, spiral
      wound TT over the FOB. Ease of TT advancement over the FOB into the trachea was
      graded on a 1 (easy) to 3 (difficult) scale, and differences between the two
      groups were compared with chi 2 analysis. The overall scores were compared with
      Wilcoxon's ranked sum test. Statistical significance was defined as P < 0.05. In
      patients randomized to the regular TT, only 35% (7/20) of first attempts to
      advance the TT over the FOB were successful. In the patients randomized to the
      spiral-wound TT, 95% (19/20) of first attempts were successful (P < 0.0001). Of
      the 13 regular TTs that were not successfully advanced on the first attempt,
      seven could not be passed after the second or third attempt (necessitating the
      use of the cross-over spiral-wound TT). In the only instance in which a spiral
      wound tube was not successfully passed into the trachea on the first attempt,
      passage also was not achieved after the second or third attempt.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8135397
TI  - Possible mechanisms for the interaction of peripheral somatic nerve stimulation,
      tissue injury, and hemorrhage in the pathophysiology of traumatic shock.

PMID- 8135398
TI  - Costs of anesthetic drugs: experiences with a cost education trial.

PMID- 8135399
TI  - Prolonged weakness after infusion of atracurium in two intensive care unit
      patients.

PMID- 8135400
TI  - Sinus arrest after intravenous neostigmine in two heart transplant recipients.

PMID- 8135401
TI  - Postoperative myoclonus and rigidity after anesthesia with opioids.

PMID- 8135402
TI  - Malignant hyperthermia--diagnostic dilemma: false-negative contracture responses
      with halothane and caffeine alone.

PMID- 8135403
TI  - Epidural fentanyl in a cystic fibrosis patient with pleuritic chest pain.

PMID- 8135404
TI  - Pneumomediastinum after planned retrograde fiberoptic intubation.

PMID- 8135405
TI  - Atrial septal aneurysm diagnosed during coronary artery bypass surgery.

PMID- 8135406
TI  - Abdominal distention is not always a sign of esophageal intubation: cardiac
      arrest due to "auto-PEEP".

PMID- 8135407
TI  - Detection of a previously undiagnosed anomalous subclavian artery during
      insertion of a transesophageal echocardiography probe.

PMID- 8135408
TI  - Intravenous nitroglycerin for intrapartum external version of the second twin.

PMID- 8135409
TI  - Operator experience as a factor in double-lumen endotracheal intubation.

PMID- 8135410
TI  - Office analgesia and suite sedation: a look at the issues.

PMID- 8135411
TI  - Bulb pump infusions and extravasation injury.

PMID- 8135412
TI  - Clamp for infusion pump.

PMID- 8135413
TI  - Fiberoptic intubation via the laryngeal mask airway.

PMID- 8135414
TI  - Ventilatory response to carbon dioxide in term infants after halothane and
      nitrous oxide anesthesia.

PMID- 8135415
TI  - Molar potency and the onset of action of rocuronium.

PMID- 8135416
TI  - Aspiration pneumonitis and the laryngeal mask airway.

PMID- 8135417
TI  - Use of the laryngeal mask airway during thoracotomy in a pediatric patient with
      cri-du-chat syndrome.

PMID- 8135418
TI  - The role of the laryngeal mask for failed tracheal intubation in the patient with
      a "full stomach".

PMID- 8135419
TI  - Hydrodynamic evaluation of intravenous infusion systems.
AB  - STUDY OBJECTIVE: We investigated the hydrodynamic characteristics of IV infusion
      sets for rapid fluid resuscitation. A simple technique has been devised for
      quantitative evaluation of the hydrodynamic characteristics of IV sets, including
      their components, for a range of infusion pressures. SETTING AND METHODS:
      Previous investigations have measured the overall flow rate of infusion sets with
      and without IV catheters. This study presents a quantitative technique for
      measuring the resistance to flow of the IV delivery set as a whole as well as its
      components. An infusion set was measured with 14- and 18-gauge IV catheters while
      delivering fluid at infusion pressures between 50 (gravity) and 400 mm Hg.
      MEASUREMENTS AND MAIN RESULTS: At gravity-driven infusion, the drip chamber
      imposes a resistance to flow of the same order as that of the catheter. At
      pressurized infusion with small-bore catheters, the catheter consumes the
      majority of the overall pressure drop. At pressurized infusion with a large-bore
      catheter or tubing, the standard drip chamber becomes the limiting component and
      imposes the largest resistance to flow. CONCLUSION: At gravity-delivered
      pressures (50 and 100 mm Hg), the only effective way of increasing flow rate
      (more than twofold) is to use a low-resistance drip chamber or to use two
      infusion sites. At pressurized delivery pressures (more than 200 mm Hg),
      increasing catheter size from 18 to 14 gauge would be more effective than
      doubling the number of infusion sets. Also, a more efficient drip chamber adds an
      important advantage. Finally, increasing the tubing diameter adds only minimal
      benefit.

PMID- 8135420
TI  - Intravenous magnesium in the treatment of hydrofluoric acid burns in rats.
AB  - STUDY OBJECTIVE: To gather preliminary data on the safety and efficacy of IV
      magnesium in a rat model of hydrofluoric acid burns. MODEL: Forty-seven
      anesthetized male rats (200 to 300 g) received a standardized burn with 52%
      hydrofluoric acid. INTERVENTIONS: Animals were anesthetized with 30 to 50 mg/kg
      ketamine IM and 1 to 3 mg/kg xylazine IM. A standardized chemical burn was
      created by topical application of 52% hydrofluoric acid. The rats were divided
      into four treatment groups: group 1 received no treatment; group 2 received
      intradermal injection of 10% calcium gluconate; group 3 received 80 mg/kg MgSO4
      IV; and group 4 received 160 mg/kg MgSO4 IV. After the rats were killed, the burn
      lesions were excised and examined by a pathologist to determine the grade of burn
      (which was equal to the clinical degree of burn). MEASUREMENTS AND MAIN RESULTS:
      Microscopic examination of the burns revealed differences among the four groups.
      Five of 13 group 1 rats (37%) died within 24 hours of burn initiation. Of group 1
      survivors, 50% had grade 2 burns, and the other 50% had grade 3 burns. In group
      2, eight of 11 rats (73%) had grade 3 burns. Twenty-five percent of group 3 rats
      (three of 12) had grade 3 burns, and only 9% of group 4 rats (one of 11) had
      grade 3 burns. Only the difference in the rates of grade 3 burns for groups 2 and
      4 was statistically significant. Although not statistically significant, burns in
      groups 3 and 4 tended to be smaller in diameter than burns in groups 1 and 2.
      CONCLUSION: High-dose IV magnesium sulfate reduces the severity of hydrofluoric
      acid burn compared with conventional intradermal calcium gluconate therapy. Early
      deaths appeared to be prevented by both calcium and magnesium therapies.

PMID- 8135421
TI  - A piglet model of status epilepticus: comparison of cardiorespiratory and
      metabolic changes with two methods of pentylenetetrazol administration.
AB  - STUDY OBJECTIVE: Impaired cardiac and respiratory responses during active tonic
      clonic convulsions (ictal periods) may contribute to complications during
      seizures. This study characterized physiologic parameters in two
      pentylenetetrazol (PTZ)-induced seizure models. PARTICIPANTS: Twelve
      spontaneously breathing piglets. INTERVENTIONS: Under ketamine anesthesia, a
      tracheostomy was performed, and an arterial catheter and epidural electrodes were
      inserted. Piglets received a PTZ bolus (100 mg/kg), with (six; 5 mg/kg/min) or
      without (six) an infusion of PTZ for 20 minutes. MEASUREMENTS AND MAIN RESULTS:
      Arterial blood gases, mean arterial pressure, heart rate, tidal volume, and EEG
      waveforms were measured. Ictal periods had high-amplitude, synchronized EEG
      activity; interictal periods had EEG suppression. Seizure duration (24 +/- 3.5
      versus 11 +/- 3.8 minutes; mean +/- SD) was significantly increased in the
      infusion group (P < .05). Significant increases in heart rate, minute
      ventilation, and base deficit plus decreases in pH occurred in both groups during
      seizures compared with baseline (P < .05). The duration and severity of metabolic
      acidosis were greater in the infusion group. During the first ten minutes of
      seizures, ten-second epochs were compared: beginning of ictal period, end of same
      ictal period, beginning of accompanying interictal period, and end of same
      interictal period. Respiratory rate decreased during initial interictal (65 +/-
      40) more than latter ictal more than latter interictal period, compared with
      initial ictal period (194 +/- 65; P < .001). Tidal volume increased during latter
      ictal more than latter interictal more than initial ictal period (33 +/- 11), but
      the greatest increases occurred during initial interictal period (140 +/- 55; P <
      .001). CONCLUSION: This model demonstrates significant increases in the duration
      and various measures of seizure severity in piglets given a PTZ infusion compared
      with those receiving a bolus alone. Systematic alterations in respiratory but not
      cardiac responses occur during ictal-interictal cycling of PTZ-induced seizures.

PMID- 8135422
TI  - Experimental amitriptyline poisoning: treatment of severe cardiovascular toxicity
      with cardiopulmonary bypass.
AB  - STUDY OBJECTIVE: To compare cardiopulmonary bypass (CPB) with more conventional
      therapy in the treatment of severe amitriptyline poisoning. DESIGN: Prospective,
      randomized, controlled, laboratory investigation. INTERVENTIONS: Profound
      cardiovascular toxicity was induced in 20 anesthetized Yorkshire swine (72 +/-
      8.3 kg) by amitriptyline infusion at 0.5 mg/kg/min. Ventilation was adjusted to
      keep arterial pH at 7.50 +/- 0.05 and the PCO2 at 35 mm Hg. The swine were
      randomized in a 1:1 ratio to one of two groups, CPB or control. Both groups
      received amitriptyline infusion until they experienced near-lethal toxicity,
      defined as a systolic blood pressure below 30 mm Hg for one minute. The control
      group was then given supportive treatment, including IV fluids, sodium
      bicarbonate, vasopressors, and standard pharmacologic (advanced cardiac life
      support) interventions. Control animals failing to respond to supportive measures
      after five minutes were given open-chest cardiac massage for 30 minutes or until
      the return of spontaneous circulation. The CPB group received only mechanical
      support by CPB for 90 to 120 minutes. No sodium bicarbonate, antiarrhythmics, or
      cardiotonic agents were provided to the CPB group during this resuscitation.
      RESULTS: All 20 animals experienced cardiac conduction delays, dysrhythmias, and
      progressive hypotension within 30 minutes of receiving IV amitriptyline at 0.5
      mg/kg/min. The ten swine receiving CPB as treatment for cardiovascular toxicity
      were able to completely correct the dysrhythmias, cardiac conduction
      abnormalities, and hypotension produced by the amitriptyline; however, only one
      of ten control animals could be resuscitated (P = .0001). Nine of ten swine
      treated with CPB were easily weaned off bypass without any pharmacologic
      intervention; however, one required norepinephrine to be weaned. All 11
      resuscitated swine were able to be salvaged. CONCLUSION: CPB improved survival in
      our swine model of severe amitriptyline poisoning.

PMID- 8135423
TI  - 4-Methylpyrazole blocks acetaminophen hepatotoxicity in the rat.
AB  - STUDY OBJECTIVE: To determine whether 4-methylpyrazole inhibits the hepatotoxic
      effects of acetaminophen in a rat model. DESIGN AND TYPE OF PARTICIPANTS: A
      nonblinded experiment using male Sprague-Dawley rats. INTERVENTIONS: Animals were
      divided into four groups. Groups 1 through 3 received 2,000 mg/kg acetaminophen
      by gavage; group 4 acted as a control. At four or eight hours, group 2 received
      400 mg/kg 4-methylpyrazole; group 3 received 50 mg/kg 4-methylpyrazole. Blood
      samples were taken for measurements of serum AST and ALT levels. Livers were
      removed for microscopic examination and grading of necrosis. RESULTS: Lower AST
      and ALT levels were obtained for both the 400-mg/kg (P < .01) and 50-mg/kg (P <
      .05) doses of 4-methylpyrazole administered four hours after acetaminophen.
      Although mean AST and ALT levels also were lower when 400 and 50 mg/kg 4
      methylpyrazole were administered eight hours after acetaminophen, these results
      were not statistically significant. Median necrosis scores were 3 for rats
      receiving acetaminophen alone, 0.5 for those receiving acetaminophen and 400
      mg/kg 4-methylpyrazole (P < .05), 1 for those receiving acetaminophen and 50
      mg/kg 4-methylpyrazole (P < .05), and 0 for control rats (P < .05). CONCLUSION:
      When administered four hours after a toxic dose of acetaminophen, 4
      methylpyrazole significantly inhibits hepatotoxicity in the rat, as reflected by
      lower levels of serum transaminases and lesser degrees of hepatic necrosis.

PMID- 8135424
TI  - Flumazenil induces seizures and death in mixed cocaine-diazepam intoxications.
AB  - STUDY HYPOTHESIS: Administration of the benzodiazepine antagonist flumazenil may
      unmask seizures in mixed cocaine-benzodiazepine intoxication. DESIGN: Male
      Sprague-Dawley rats received 100 mg/kg cocaine IP alone, 5 mg/kg diazepam alone,
      or a combination of diazepam and cocaine. Three minutes later, groups were
      challenged with vehicle or flumazenil 5 or 10 mg/kg IP. Animal behavior, seizures
      (time to and incidence), death (time to and incidence), and cortical EEG tracings
      were recorded. INTERVENTIONS: Administration of flumazenil to animals after they
      had received a combination dose of cocaine and diazepam. RESULTS: In group 1,
      animals received cocaine followed by vehicle. This resulted in 100% developing
      seizures and death. Group 2 received diazepam alone followed by vehicle. Animals
      became somnolent and none died. Group 3 received diazepam followed by 5 mg/kg
      flumazenil. Animals became somnolent after diazepam and then active after
      flumazenil administration. In group 4, a combination of cocaine and diazepam was
      administered simultaneously. This resulted in no overt or EEG-detectable seizures
      and a 50% incidence of death. Group 5 received a similar combination of cocaine
      and diazepam, followed later by 5 mg/kg flumazenil. This resulted in an increased
      incidence of seizures, 90% (P < .01), and death, 100% (P < or = .01), compared
      with group 4. Group 6 received cocaine and diazepam followed by 10 mg/kg
      flumazenil. This also resulted in an increased incidence of seizures, 90% (P < or
      = .01), and death, 90% (P < or = .05), compared with group 4. CONCLUSION:
      Flumazenil can unmask seizures and increase the incidence of death in a model of
      combined cocaine-diazepam intoxications.

PMID- 8135425
TI  - Hemodynamic effects of 3,4-diaminopyridine in a swine model of verapamil
      toxicity.
AB  - STUDY HYPOTHESIS: 3,4-Diaminopyridine (3,4-DAP) may reverse the hemodynamic
      effects of severe verapamil toxicity. DESIGN: A nonblinded acute animal
      preparation. INTERVENTIONS: Eighteen chloralose-anesthetized and instrumented
      swine were poisoned with verapamil at 10 mg/kg/hr for five minutes and then 5
      mg/kg/hr until a systolic blood pressure of 55 mm Hg was achieved. Heart rate,
      lead II ECG, mean arterial pressure, left ventricular dP/dT max, and cardiac
      index were monitored. Nine control animals received 0.2 mL/kg/min infusion of
      normal saline, and nine treatment animals received similar volumes of 1 mg/kg/min
      3,4-DAP until systolic blood pressure reached 100 mm Hg, an elapsed time of 30
      minutes, or death. RESULTS: Verapamil toxicity was produced in all animals
      following an average dose of 1.38 +/- 0.44 mg/kg verapamil, and resulted in
      diminished mean arterial pressure, dP/dT max, cardiac index, and heart rate to
      average values of 47%, 32%, 46%, and 88% of baseline values, respectively.
      Transient atrioventricular dissociation was noted in only 22% of cases. 3,4-DAP
      treatment (with an average dose of 14 +/- 5.6 mg/kg) resulted in significant
      increases in mean arterial pressure, dP/dT max, cardiac index, and heart rate to
      136%, 298%, 149%, and 158% of baseline values, respectively. Mortality was
      unchanged (22% in both groups). 3,4-DAP treatment was complicated by muscle
      twitching, tachycardia (rate of more than 180) and hypertension (diastolic blood
      pressure of more than 110 mm Hg) each in 44% of cases. CONCLUSION: Although 3,4
      DAP reversed the hypotensive and negative inotropic effects of verapamil
      toxicity, it failed to improve survival and resulted in several complications
      including muscle twitching, tachycardia, and hypertension.

PMID- 8135426
TI  - The lack of efficacy of phenytoin in the prevention of recurrent alcohol-related
      seizures.
AB  - STUDY OBJECTIVE: To determine the effectiveness of IV phenytoin in the prevention
      of recurrent alcohol-related seizures during a six-hour observation period.
      DESIGN: Prospective, randomized, double-blind trial comparing IV phenytoin with
      normal saline placebo, conducted from January 1990 through December 1991.
      SETTING: Emergency department of an inner-city, university-affiliated, teaching
      hospital. PARTICIPANTS: One hundred forty-seven consecutive adults more than 25
      years of age who presented with a witnessed generalized seizure in the setting of
      chronic alcohol abuse. INTERVENTIONS: Eligible subjects received 15 mg/kg of
      phenytoin or normal saline at an equivalent volume over 20 minutes by IV pump.
      Patients were observed for six hours in the ED after drug administration. Those
      experiencing a second seizure were admitted to the hospital. RESULTS: One hundred
      patients completed the study. Recurrent alcohol-related seizures occurred in ten
      of 49 patients (20.4%) in the phenytoin group and in 12 of 51 patients (23.5%) in
      the placebo group. chi 2 analysis revealed no statistically significant
      difference between the two groups (chi 2 = 0.142; P = .706). The 95% confidence
      interval for the difference was -0.13 to + 0.19. The relative risk of recurrence
      between groups was 0.868 with a 95% confidence interval of 0.412 to 1.826.
      CONCLUSION: No significant benefit of phenytoin administration in the prevention
      of recurrent alcohol-related seizures during a six-hour observation period was
      demonstrated.

PMID- 8135427
TI  - A prospective evaluation of the effect of activated charcoal before oral N
      acetylcysteine in acetaminophen overdose.
AB  - STUDY OBJECTIVE: To evaluate whether activated charcoal (AC) reduces the efficacy
      of subsequent oral N-acetylcysteine therapy during acute acetaminophen overdose.
      DESIGN: Prospective observational case series of all acute acetaminophen
      overdoses reported to three certified regional poison centers. TYPES OF PATIENTS:
      All patients with acute acetaminophen overdose in whom N-acetylcysteine therapy
      was initiated within 16 hours after ingestion. INTERVENTIONS: All patients were
      treated with oral N-acetylcysteine therapy for 72 hours. The decision to use AC
      was left to the treating physician without input from the investigator.
      MEASUREMENTS AND RESULTS: One hundred twenty-two patients were evaluated. Maximum
      recorded SGOT levels of more than 125 U/mL were defined as evidence of
      hepatotoxicity. AC was used in addition to N-acetylcysteine in 82 of 122
      patients. Hepatotoxicity developed in four of 82 patients who received AC versus
      ten of 40 patients who did not receive AC (P < .005). An increasing dose of N
      acetylcysteine provided no additional benefit (P > .05). Spacing the
      administration of AC and oral N-acetylcysteine less than or more than two hours
      apart did not affect outcome (P > .05). CONCLUSION: Administration of AC before
      the administration of oral N-acetylcysteine in acetaminophen overdose does not
      reduce the efficacy of N-acetylcysteine therapy and may provide some additional
      hepatoprotective benefit. The practice of increasing the dose of oral N
      acetylcysteine therapy after the administration of AC appears unwarranted.

PMID- 8135428
TI  - The effect of 25 grams i.v. glucose on serum inorganic phosphate levels.
AB  - STUDY OBJECTIVE: To determine whether a 25-g IV glucose bolus will result in a
      fall in serum inorganic phosphate levels. DESIGN: Single-blind, randomized,
      controlled trial. PARTICIPANTS: Thirty-six healthy, nondiabetic, adult
      volunteers. INTERVENTIONS: Random allocation to a control group receiving a 50-mL
      normal saline bolus followed by a normal saline infusion at 125 mL/hr for three
      hours; study group 1, receiving a 50-mL bolus of D50W followed by a normal saline
      infusion at 125 mL/hr for three hours; or study group 2, receiving a 50-mL bolus
      of D50W followed by an infusion of 2/3:1/3 dextrose:saline solution at 125 mL/hr
      for three hours. MEASUREMENTS AND MAIN RESULTS: Serum inorganic phosphate levels
      were measured at time zero (baseline) and at 30-minute intervals for three hours.
      There was a statistically significant fall in serum inorganic phosphate levels in
      both groups receiving the glucose bolus. The group receiving the glucose infusion
      demonstrated a trend toward a further decline in serum phosphate levels.
      CONCLUSION: A glucose bolus and infusion in the amounts compatible with what is
      given to patients with altered levels of consciousness produced a significant
      fall in serum inorganic phosphate levels in healthy, nondiabetic adults. Because
      hypophosphatemia may create a clinical picture of altered mental status very
      similar to that of hypoglycemia, consideration should be given to administering
      IV glucose only to patients with finger-stick-proven hypoglycemia. Consideration
      also should be given to monitoring phosphate levels after administration of IV
      glucose.

PMID- 8135429
TI  - Antibiotics to prevent infection in patients with dog bite wounds: a meta
      analysis of randomized trials.
AB  - STUDY OBJECTIVES: To determine whether prophylactic antibiotics prevent infection
      in patients with dog bite wounds. DESIGN: Meta-analysis of published studies.
      METHODS: A literature search was performed to identify published, randomized
      trials of prophylactic antibiotics for dog bite wounds. The relative risk for
      infection in treated patients compared with controls was used as the measure of
      effect, and a summary relative risk was calculated. RESULTS: Eight randomized
      trials were identified. The estimated cumulative incidence of infection in
      controls was 16%. The relative risk for infection in patients given antibiotics
      compared with controls was 0.56 (95% confidence interval, 0.38 to 0.82). About 14
      patients must be treated to prevent one infection. CONCLUSION: Prophylactic
      antibiotics reduce the incidence of infection in patients with dog bite wounds.
      The full costs and benefits of antibiotics in this situation are not known. It
      may be reasonable to limit prophylactic antibiotics to patients with wounds that
      are at high risk for infection.

PMID- 8135430
TI  - Intravenous access in the critically ill trauma patient: a multicentered,
      prospective, randomized trial of saphenous cutdown and percutaneous femoral
      access.
AB  - STUDY OBJECTIVE: To compare the speed of IV access and the rate of infusion for
      saphenous venous cutdown and percutaneous femoral catheterization. DESIGN:
      Prospective, randomized, multicentered trial. Patient enrollment occurred from
      September 1990 through September 1991. SETTING: Patients were enrolled at three
      urban Level I trauma centers. TYPE OF PARTICIPANTS: Seventy-eight critically ill
      trauma patients. INTERVENTIONS: Participants were randomized to one of two
      groups: saphenous cutdown or percutaneous femoral line. After successful
      cannulation of the vein, 1 L of crystalloid was infused by gravity. RESULTS: The
      mean procedure time for the cutdown group was 5.63 +/- 2.58 minutes compared with
      3.18 +/- 1.19 minutes for the femoral line group (P < .0001). The mean infusion
      time for the cutdown group was 6.65 +/- 4.29 minutes compared with 4.56 +/- 2.47
      minutes for the femoral line group (P < .03). The mean overall time for the
      cutdown group was 11.76 +/- 4.81 minutes compared with 7.67 +/- 2.78 minutes for
      the femoral line group (P < .0002). CONCLUSION: Percutaneous femoral
      catheterization can be performed more rapidly than saphenous cutdown in the
      critically ill trauma patient with a palpable femoral pulse and allows for more
      rapid fluid administration. We support the use of a percutaneous femoral line as
      an acceptable alternative to saphenous venous cutdown in the initial
      resuscitation of trauma patients.

PMID- 8135431
TI  - Emergency department procedures and length of stay for critically ill medical
      patients.
AB  - STUDY OBJECTIVE: To date, the study of critical illness in the emergency
      department has been limited. The purpose of this study was to determine the ED
      length of stay and procedures performed in medical critical care patients.
      DESIGN: Descriptive study of a prospective single cohort. SETTING: Large urban
      public hospital. TYPES OF PARTICIPANTS: Fifty consecutive ED patients
      subsequently admitted to the medical ICU. MEASUREMENTS AND MAIN RESULTS: The
      study population consisted of 24 women and 26 men. The mean ED stay was 284.5 +/-
      212.6 minutes (median, 255 minutes; interquartile range [IQR], 115 to 355
      minutes). Patients remained in the ED after administrative transfer of their care
      to the medical ICU an average of 75 +/- 71.4 minutes (range, 10 to 375 minutes;
      median, 50 minutes; IQR, 25 to 105 minutes). Forty-one of these patients (82%)
      received one or more critical care procedures. The mean time to performance of
      first procedure was 92.8 +/- 180.6 minutes (median, 23 minutes; IQR, 11 to 82
      minutes) from ED arrival. Death after ICU admission occurred in 11 patients. Mean
      ED length of stay was 291 +/- 269.8 minutes (range, 35 to 980 minutes; median,
      135 minutes; IQR, 85 to 467 minutes) in nonsurvivors, and 91% of them received
      procedures in the ED. Survivors averaged 282.4 +/- 193.4 minutes (range, 15 to
      230 minutes; median, 263 minutes; IQR, 126 to 355 minutes) (P = NS) and 79.5% (P
      = NS) received ED procedures. CONCLUSION: Critically ill patients spend a
      substantial amount of time in the ED before transfer to the ICU. Typical ICU
      procedures are commonly performed. Further study of the impact on patient outcome
      of ED stay and the procedures performed in critically ill medical patients should
      be conducted.

PMID- 8135432
TI  - Reducing the pain of local anesthetic infiltration: warming and buffering have a
      synergistic effect.
AB  - STUDY OBJECTIVE: To compare room-temperature unbuffered lidocaine, warm
      lidocaine, buffered lidocaine, and warm buffered lidocaine to determine which of
      the four solutions is least painful during infiltration. DESIGN: Randomized,
      controlled, double-blinded, volunteer study. TYPE OF PARTICIPANT: Thirty-two
      young healthy adults. MAIN RESULTS: Each subject received four subcutaneous
      injections of 1% lidocaine: room-temperature unbuffered, warm, buffered, and warm
      buffered. After each injection, participants recorded their perception of pain
      associated with infiltration of the solution on a visual analog scale. Mean pain
      scores for the four solutions were determined and analyzed. The mean perceived
      pain score for the warm buffered solution was significantly lower than for any of
      the other solutions (versus warm: P = .0005; versus buffered: P = .0028; versus
      room temperature: P = .0001). There was no statistically significant difference
      between either the warm solution or buffered solution and the room-temperature
      unbuffered lidocaine. The difference in mean pain score for the warm buffered
      solution, compared with those for the warm, buffered, and room-temperature
      solutions, suggests that warming and buffering have a synergistic effect.
      CONCLUSION: Skin infiltration with warm buffered lidocaine is significantly less
      painful than infiltration with room-temperature unbuffered lidocaine, warm
      lidocaine, or buffered lidocaine.

PMID- 8135433
TI  - Impact of Yankee Stadium Bat Day on blunt trauma in northern New York City.
AB  - STUDY OBJECTIVE: To determine the incidence of blunt trauma in northern New York
      City before and after the distribution of 25,000 baseball bats at Yankee Stadium.
      DESIGN: Prospective multicenter study, including ten days before and ten days
      after Bat Day (June 3, 1990). SETTING: Ten emergency departments in the Bronx and
      northern Manhattan. TYPE OF PARTICIPANT: All patients presenting to the ED with
      baseball bat injuries. INTERVENTIONS: Each hospital collected the following data
      for each subject: date and time of injury, patient's age and sex, extent of
      injury, whether a Yankee bat was used, presence of loss of consciousness, results
      of computed tomography scan of the brain (if performed), history source, and
      disposition of the patient. Average daily atmospheric temperature was recorded
      for each day of the study. MEASUREMENTS AND MAIN RESULTS: Seventy-seven patients
      sustained bat injuries, 38 (49%) before and 36 (47%) after Bat Day. There were no
      significant differences between the two groups with respect to age, sex, time of
      injury, number and distribution of fractures and lacerations, incidence of loss
      of consciousness, source of history, or dispostion. There was a positive
      association between the number of cases on a given day and the average
      temperature that day (r = .5; P < .01). CONCLUSION: The distribution of 25,000
      wooden baseball bats to attendees at Yankee Stadium did not increase the
      incidence of bat-related trauma in the Bronx and northern Manhattan. There was a
      positive correlation between daily temperature and the incidence of bat injury.
      The informal but common impressions of emergency clinicians about the cause-and
      effect relationship between Bat Day and bat trauma were unfounded.

PMID- 8135434
TI  - Correlation of end-tidal CO2 measurements to arterial PaCO2 in nonintubated
      patients.
AB  - STUDY OBJECTIVE: To determine the accuracy of end-tidal carbon dioxide levels as
      a measure of arterial carbon dioxide levels in nonintubated patients presenting
      to an emergency department for care. DESIGN: A prospective, cross-sectional
      analysis. SETTING: University hospital ED. TYPE OF PARTICIPANT: Nonintubated
      adult patients presenting to the ED for care of a variety of problems.
      INTERVENTIONS: Patients who had arterial blood gas samples taken as part of their
      ED evaluation were asked to breathe normally through an endotracheal tube adapter
      or a modified nasal cannula connected to a side port sampling capnometer while a
      sample for arterial blood gas was drawn from the radial artery. MEASUREMENTS: End
      tidal carbon dioxide levels (mm Hg) were recorded at the time of arterial blood
      gas sampling. The difference between end-tidal carbon dioxide and PaCO2 was
      tested with the paired t-test at a significance level of .05. The correlation of
      end-tidal carbon dioxide to PaCO2 was tested in all patients and in subgroups
      using simple linear regression. RESULTS: Seventy-six patients were enrolled. In
      all patients, end-tidal carbon dioxide was 3.5 mm Hg lower than PaCO2 and
      correlated well with PaCO2 (r2 = .772). In patients with hypocapnia, there was no
      significant difference between end-tidal carbon dioxide and PaCO2 (P = .17), and
      the correlation of end-tidal carbon dioxide to PaCO2 was stronger (r2 = .838). In
      patients with a respiratory or metabolic acidosis, the difference between end
      tidal carbon dioxide and PaCO2 was 6 mm Hg (P = .005), but end-tidal carbon
      dioxide correlated well to PaCO2 (r2 = .899). CONCLUSION: Measurements of end
      tidal carbon dioxide concentrations correlate well with PaCO2 values in
      nonintubated patients presenting with a variety of conditions to EDs. End-tidal
      carbon dioxide measurements may be sufficient measures of PaCO2 in selected
      patients and obviate the need for repeat arterial blood gas determination.
      Further study is warranted.

PMID- 8135435
TI  - Trendelenburg position and oxygen transport in hypovolemic adults.
AB  - STUDY OBJECTIVE: To evaluate the effect of the Trendelenburg position on oxygen
      transport in hypovolemic patients. DESIGN: A prospective, self-controlled
      sequential design. INTERVENTIONS: All patients had indwelling pulmonary artery
      catheters, and hypovolemia was confirmed by a pulmonary artery wedge pressure of
      6 mm Hg or less. Hemodynamic and oxygen transport variables were measured with
      the patient supine and again ten minutes after placing the patient in the
      Trendelenburg position. SETTING: University-affiliated tertiary care surgical
      ICU. TYPE OF PARTICIPANTS: Eight postoperative adults. RESULTS: Mean arterial
      blood pressure increased from 64.9 +/- 4.9 to 75.6 +/- 3.5 mm Hg (P < .05),
      pulmonary artery wedge pressure increased from 4.6 +/- 1.1 to 7.9 +/- 0.8 mm Hg
      (P < .05), and the systemic vascular resistance rose to 2,965 +/- 210 from 2,302
      +/- 199 dyne.sec/cm5 (P < .05). There was no significant change in cardiac index,
      oxygen delivery, oxygen consumption, or oxygen extraction ratio. CONCLUSION: The
      increase in blood pressure from Trendelenburg position is not associated with an
      improvement in blood flow or tissue oxygenation.

PMID- 8135437
TI  - Prophylactic antibiotics in dog bite wounds: nipping at the heels of progress.

PMID- 8135436
TI  - End-tidal carbon dioxide during extremely low cardiac output.
AB  - STUDY OBJECTIVE: A number of studies have shown that expired CO2 concentration is
      closely related to cardiac output, but that cardiac output was not controlled as
      an independent variable. In addition, the partial pressure of end-tidal CO2
      (PETCO2) during extremely low cardiac output has not been reported. The objective
      of the present study was to measure PETCO2 during well-controlled, very low blood
      flow rates under conditions of constant minute ventilation. DESIGN: Ten
      anesthetized, intubated, and mechanically ventilated swine (weight, 43 to 102 kg)
      were placed on two ventricular assist devices in order to control cardiac output.
      Minute ventilation was measured and kept constant. Ventricular assist device
      output (measured with an ultrasonic flow probe); PETCO2; and aortic, pulmonary
      artery, and central venous pressures were recorded continuously. INTERVENTIONS:
      After electrical induction of ventricular fibrillation, pump output was decreased
      in steps. MEASUREMENTS AND MAIN RESULTS: Cardiac index ranged from 0 to 5,371
      mL/min/m2; 59% of PETCO2 measurements were made at cardiac indexes of less than
      1,313 mL/min/m2 (30 mL/min/kg). The relationship of PETCO2 levels to cardiac
      index was determined with linear regression analysis; P < .05 was statistically
      significant. PETCO2 correlated significantly with cardiac index (P < .0001). The
      best-fit line by least-squares analysis produced the equation: PETCO2 = 4.98 +
      0.012 [cardiac index] (r2 = .82). CONCLUSION: Under conditions of constant minute
      ventilation, PETCO2 correlated closely with cardiac index over a large range of
      blood flow rates, including extremely low rates.

PMID- 8135438
TI  - The use of acetone to dissolve a Styrofoam impaction of the ear.
AB  - Foreign bodies in the ear occasionally thwart conventional means of removal.
      Styrofoam can be particularly problematic because it can be compressed and become
      tightly impacted in an ear canal. Furthermore, Styrofoam is friable and tends to
      fragment with usual removal methods. We report the case of a 6-year-old girl who
      was referred from another tertiary care hospital after failed efforts to remove a
      painfully impacted piece of Styrofoam from her left ear canal. Instillation of
      the organic solvent acetone into the ear canal was well tolerated and caused
      rapid and near-complete dissolution of the Styrofoam impaction. This is the first
      reported case of organic solvent dissolution of an otic foreign body. Ototoxic
      considerations are discussed as is a method for safe acetone instillation that
      minimizes the amount of acetone introduced into the ear canal.

PMID- 8135439
TI  - Rhabdomyolysis with pericardial tamponade.
AB  - A young man developed an acute illness and presented to the hospital in shock. On
      admission, both severe rhabdomyolysis and pericardial tamponade were present, the
      tamponade occurring as a complication of pericarditis. Echocardiography was
      required for rapid diagnosis of the cardiac tamponade. The etiology of this
      severe, life-threatening illness is discussed.

PMID- 8135440
TI  - Mixed fluoxetine/loxapine overdose and atrial flutter.
AB  - A 19-year-old man who attempted suicide by ingesting approximately 600 mg
      fluoxetine (Prozac) and 140 mg loxapine (Loxitane) had two episodes of atrial
      flutter shortly thereafter. Admission serum fluoxetine, norfluoxetine, and
      loxapine levels were 1,053 ng/mL, 702 ng/mL, and 40 ng/mL, respectively. This
      case of atrial flutter in association with an overdose of either of these drugs
      demonstrates the potential for cardiotoxicity with these agents in the overdose
      setting. Theoretical mechanisms of cardiotoxicity are presented.

PMID- 8135442
TI  - I was never afraid.

PMID- 8135441
TI  - Subglottic airway hemorrhage associated with idiopathic thrombocytopenic purpura.
AB  - A case of subglottic airway hemorrhage in a 6-year-old child with acute
      idiopathic thrombocytopenic purpura is presented. No previous cases have been
      reported in which idiopathic thrombocytopenic purpura was associated with this
      life-threatening complication. In this case, stridor responded to racemic
      epinephrine and oxygen. Emergency physicians and pediatricians should be aware of
      this rare complication.

PMID- 8135443
TI  - Infants and children with fever without source.

PMID- 8135444
TI  - TAC gel--a sterile formulation.

PMID- 8135445
TI  - Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A
      randomized controlled trial.
AB  - OBJECTIVE: To test whether intermittent treatment with slow-release sodium
      fluoride and continuous calcium citrate supplementation inhibits vertebral
      fractures without causing fluoride complications. DESIGN: A placebo-controlled,
      randomized trial. SETTING: Outpatient setting of specialty clinics in Dallas and
      Temple, Texas. INTERVENTIONS: Slow-release sodium fluoride (25 mg twice daily) in
      repeated 14-month cycles (12 months on treatment followed by 2 months off
      treatment) compared with placebo. Both groups took calcium citrate (400 mg
      calcium twice daily) continuously. PATIENTS: 110 patients with postmenopausal
      osteoporosis were randomly assigned to two groups. In the slow-release sodium
      fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean,
      2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at
      least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis. MEASUREMENTS:
      Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were
      quantified from yearly radiographs. Bone mass was determined annually by
      densitometry. RESULTS: In the sodium fluoride group, the mean L2 to L4 bone
      mineral content increased by 4% to 6% in each cycle and the mean femoral neck
      bone density increased by 4.1% and 2.1% during the first two cycles, but the
      radial bone density did not change. The placebo group showed no statistical
      change in bone mass at any site. Compared with the placebo group, the sodium
      fluoride group had a lower individual new vertebral fracture rate (0.057/patient
      cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate
      (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate
      (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side
      effect profile was similar for the two groups; no patient developed
      microfractures, hip fractures, or blood loss anemia. CONCLUSIONS: Intermittent
      slow-release sodium fluoride plus continuous calcium citrate, administered for
      about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone
      mass without decreasing the radial shaft bone density, and is safe to use.

PMID- 8135446
TI  - Can bruits distinguish high-grade from moderate symptomatic carotid stenosis? The
      North American Symptomatic Carotid Endarterectomy Trial.
AB  - OBJECTIVE: To determine whether cervical bruits, alone or combined with other
      clinical characteristics, can distinguish high-grade (70% to 99%) carotid artery
      stenoses from less severe stenoses in patients with symptoms of cerebrovascular
      disease. DESIGN: Cross-sectional comparison of clinical observations with
      contemporaneous angiography. SETTING: The North American Symptomatic Carotid
      Endarterectomy Trial (NASCET), a multicenter randomized controlled trial of
      carotid endarterectomy. PATIENTS: All patients enrolled in the NASCET from its
      inception in 1988 to November 1991. RESULTS: A focal ipsilateral carotid bruit
      had a sensitivity of 63% and a specificity of 61% for high-grade stenosis and,
      when absent, only lowered the probability for high-grade stenosis from a pretest
      value of 52% to a post-test probability of 40%. When combined with four other
      clinical characteristics (an infarction on computed tomography of the head, a
      carotid ultrasound scan suggesting more than 90% stenosis, a transient ischemic
      attack rather than a minor stroke as a qualifying event, and a retinal rather
      than a hemispheric qualifying event), the predicted probabilities of high-grade
      stenosis ranged from a low of 18% (when none of the features was present) to a
      high of 94% (when all the features were present. CONCLUSIONS: Cervical bruits
      alone were not sufficiently predictive of high-grade symptomatic carotid stenosis
      to be useful in selecting patients for angiography; they were absent in over one
      third of patients with high-grade stenosis. When combined with other clinical
      variables, patients with high or low probabilities of 70% to 99% stenoses could
      be identified, but this prediction model still missed many individuals with high
      grade stenosis, even in this training set of selected patients.

PMID- 8135447
TI  - Comparison of clinical outcomes for women and men after acute myocardial
      infarction. The Thrombolysis in Myocardial Infarction Investigators.
AB  - OBJECTIVES: To assess differences in morbidity and mortality between men and
      women with acute myocardial infarction treated with thrombolytic therapy and the
      relation of differences to baseline patient characteristics and clinical
      features. DESIGN: Secondary analysis of observational findings among women and
      men enrolled in a clinical trial. SETTING: Hospitals participating in the
      Thrombolysis in Myocardial Infarction Phase II trial. MEASUREMENTS: Recurrent
      infarctions and deaths were assessed. MAIN RESULTS: The 6-week mortality rate was
      greater for women than for men (9% compared with 4%; adjusted relative risk,
      1.54; P = 0.01). Death or reinfarction occurred in 15.9% of women and 9.5% of men
      (adjusted relative risk, 1.33; P = 0.02). Among patients enrolled for treatment
      with 100 mg of recombinant tissue plasminogen activator and assigned to a
      conservative strategy of watchful waiting with appropriate backup, the 6-week
      incidence of death was 7.5% for women and 3.8% for men (P = 0.01). The 6-week
      incidences of death or reinfarction were 14.2% and 8.9% (P = 0.01) among women
      and men, respectively. CONCLUSIONS: Among patients in the Thrombolysis in
      Myocardial Infarction Phase II Trial, who all were diagnosed with myocardial
      infarction and were eligible to receive thrombolytic therapy, women had higher
      rates of mortality and morbidity than did men. Older age at the time of
      myocardial infarction and a history of diabetes accounted for much but probably
      not all of this difference.

PMID- 8135448
TI  - Identical-twin bone marrow transplants for leukemia.
AB  - OBJECTIVE: To compare outcomes of identical-twin with HLA-identical sibling bone
      marrow transplants for leukemia. DESIGN: Matched-pair analysis comparing relapse,
      treatment-related mortality, and leukemia-free survival in cohorts matched for
      disease and variables correlated with transplant outcome, with and without
      adjustment for graft-versus-host disease. SETTING: 163 institutions worldwide
      between 1978 and 1990, reporting to the International Bone Marrow Transplant
      Registry. PARTICIPANTS: 103 identical-twin transplants: 24 for acute
      lymphoblastic leukemia (ALL) in first remission, 45 for acute myelogenous
      leukemia (AML) in first remission, and 34 for chronic myelogenous leukemia (CML)
      in first chronic phase. Results were compared with those in 1030 concurrent HLA
      identical sibling transplants matched for prognostic factors. RESULTS: Three-year
      probabilities of relapse after identical-twin compared with HLA-identical sibling
      transplants were as follows: ALL, 36% (95% CI, 17% to 55%) compared with 26% (CI,
      20% to 32%); AML, 52% (CI, 37% to 67%) compared with 16% (CI, 12% to 20%); and
      CML, 40% (CI, 23% to 57%) compared with 7% (CI, 4% to 10%). Increased relapse
      risks in AML and CML persisted after adjusting for graft-versus-host disease
      (relative risk, 3.1 [CI, 1.9 to 5.1] and 5.5 [CI, 2.8 to 11.0], respectively).
      Although twins had less treatment-related mortality than HLA-identical siblings,
      leukemia-free survival was similar. Three-year leukemia-free survival
      probabilities after twin compared with HLA-identical sibling transplants were as
      follows: ALL, 57% (CI, 37% to 77%) compared with 58% (CI, 52% to 64%); AML, 42%
      (CI, 27% to 57%) compared with 55% (CI, 50% to 60%); and CML, 59% (CI, 42% to
      76%) compared with 61% (CI, 56% to 66%). CONCLUSIONS: Identical-twin transplants
      in AML and CML are associated with increased relapse risk compared with HLA
      identical sibling transplants. A similar trend was observed in ALL but was not
      statistically significant. Increased relapse in twin transplants is not explained
      by lack of graft-versus-host disease. Leukemia-free survival after twin and HLA
      identical sibling transplants is similar because increased relapse in twins is
      offset by decreased treatment-related mortality.

PMID- 8135449
TI  - Nosocomial pneumonia in mechanically ventilated patients receiving antacid,
      ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized
      controlled trial.
AB  - OBJECTIVE: To assess three anti-stress ulcer prophylaxis regimens in mechanically
      ventilated patients for bacterial colonization, early- and late-onset nosocomial
      pneumonia, and gastrointestinal bleeding. DESIGN: Randomized controlled trial.
      PATIENTS: Consecutive eligible patients with mechanical ventilation and a
      nasogastric tube. Of 258 eligible patients, 244 were assessable. SETTING: Medical
      and surgical intensive care units. INTERVENTION: At intubation, patients were
      randomly assigned to receive one of the following: antacid (a suspension of
      aluminum hydroxide and magnesium hydroxide), 20 mL every 2 hours; ranitidine, 150
      mg as a continuous intravenous infusion; or sucralfate, 1 g every 4 hours.
      MEASUREMENTS: Using predetermined criteria, the incidence of gastric bleeding,
      gastric colonization, early-onset pneumonia, and late-onset pneumonia was
      assessed in patients intubated for more than 24 hours. RESULTS: Of 244 assessable
      patients, macroscopic gastric bleeding was observed in 10%, 4%, and 6% of
      patients assigned to receive sucralfate, antacid, and ranitidine, respectively (P
      > 0.2). The incidence of early-onset pneumonia was not statistically different
      among the three treatment groups (P > 0.2). Among the 213 patients observed for
      more than 4 days, late-onset pneumonia was observed in 5% of the patients who
      received sucralfate compared with 16% and 21% of the patients who received
      antacid or ranitidine, respectively (P = 0.022). Mortality was not statistically
      different among the three treatment groups. Patients who received sucralfate had
      a lower median gastric pH (P < 0.001) and less frequent gastric colonization
      compared with the other groups (P = 0.015). Using molecular typing, 84% of the
      patients with late-onset gram-negative bacillary pneumonia were found to have
      gastric colonization with the same bacteria before pneumonia developed.
      CONCLUSION: Stress ulcer prophylaxis with sucralfate reduces the risk for late
      onset pneumonia in ventilated patients compared with antacid or ranitidine.

PMID- 8135450
TI  - Calcium antagonist-induced gingival hyperplasia.

PMID- 8135451
TI  - Fulminant hepatic failure from a sea anemone sting.

PMID- 8135453
TI  - Grass roots participation in health care reform.
AB  - Concerned citizens have responded to the health care crisis by developing the
      health decisions movement. American Health Decisions, a national consortium of 21
      state organizations, leads a grass roots discussion network of community meetings
      committed to education and consensus on the ethical, technologic, legal, and
      economic issues (the tough issues) of health policy. The movement (with its
      stages of development, structure, process, and accomplishments) is described, and
      potential roles for physician cooperation and participation in forging
      functional, community-based health policy are delineated.

PMID- 8135452
TI  - Guidelines for meta-analyses evaluating diagnostic tests.
AB  - OBJECTIVES: To introduce guidelines for the conduct, reporting, and critical
      appraisal of meta-analyses evaluating diagnostic tests and to apply these
      guidelines to recently published meta-analyses of diagnostic tests. DATA SOURCES:
      Based on current concepts of how to assess diagnostic tests and conduct meta
      analyses. They are applied to all meta-analyses evaluating diagnostic tests
      published in English-language journals from January 1990 through December 1991,
      identified through MEDLINE searching and by experts in the field. STUDY
      SELECTION: Meta-analyses were included if at least two of three independent
      readers regarded their main purpose as the evaluation of diagnostic tests against
      a concurrent reference standard. DATA EXTRACTION: By three independent readers on
      the extent to which meta-analyses fulfilled each guideline, with consensus
      defined as agreement by at least two readers. DATA SYNTHESIS: The guidelines are
      concerned with determining the objective of the meta-analysis, identifying the
      relevant literature and extracting the data, estimating diagnostic accuracy, and
      identifying the extent to which variability is explained by study design
      characteristics and characteristics of the patients and diagnostic test. In
      general, the guidelines were only partially fulfilled. CONCLUSION: Meta-analysis
      is potentially important in the assessment of diagnostic tests. Those reading
      meta-analyses evaluating diagnostic tests should critically appraise them; those
      doing meta-analyses should apply recently developed methods. The conduct and
      reporting of primary studies on which meta-analyses are based require
      improvement.

PMID- 8135454
TI  - What is the Oslerian tradition?
AB  - Discussants of internal medicine often invoke but seldom define "the Oslerian
      tradition," which has many meanings. No definition provides clear insight into
      the issues now relevant to American internal medicine, primarily because, as
      William Osler knew, the field itself shows definitional ambivalence. The
      tradition might be best understood as a virtuous approach to medicine and to life
      as taught and modeled by Osler. If we understand his philosophy and methods, we
      will be better prepared to use and pass on (tradere, "to deliver") something of
      greater value: the ability to make wise choices that are in society's best
      interest.

PMID- 8135455
TI  - To respond always.

PMID- 8135456
TI  - Fluoride and osteoporosis.

PMID- 8135457
TI  - Potential risk of prolonged gamma-linolenic acid use.

PMID- 8135458
TI  - Thrombocytopenia and illicit drug use.

PMID- 8135459
TI  - Prednisone in managing rheumatoid arthritis.

PMID- 8135460
TI  - Death from an unconventional therapy for AIDS.

PMID- 8135461
TI  - Primary selective IgA deficiency.

PMID- 8135462
TI  - Myocardial infarction in a patient who smoked while wearing a nicotine patch.

PMID- 8135463
TI  - Simplified bedside thoracentesis.

PMID- 8135464
TI  - Atrial myxoma mimicking Lyme disease.

PMID- 8135465
TI  - Case reports and causality.

PMID- 8135466
TI  - Surgeons and internists.

PMID- 8135467
TI  - Rewarding women in academic medicine.

PMID- 8135468
TI  - A phase II multi-institutional study of estra-1,3,5(10)-triene-3,17 beta-diol, 3
      benzoate, 17[[4-[4-[bis(2-chloroethyl)amino]phenyl]-1- oxobutoxy]acetate]
      (KM2210), a novel antitumor agent, for advanced and recurrent breast carcinoma.
AB  - In order to evaluate the efficacy of Estra-1,3,5(10)-Triene-3,17 beta-Diol, 3
      Benzoate, 17[[4-[4-[Bis(2-Chloroethyl) Amino]Phenyl]-1-Oxobutoxy] Acetate]
      (KM2210), a multi-institutional cooperative Phase II study was performed in
      patients with measurable advanced and recurrent breast cancer. Two hundred
      miligrams of KM2210, a conjugate of chlorambucil and 17 beta-estradiol, were
      administered orally daily for more than 4 weeks to each patient. According to the
      WHO criteria of response, 103 evaluable cases were assessed. Complete response
      was obtained in 9 cases, partial response in 19, no change in 39 and progressive
      disease was observed in 36. The overall response rate was 27.2% (28/103). The
      response rate was higher in patients without prior treatment than in those with
      prior treatment. However, KM2210 was also effective against breast cancers
      treated previously with tamoxifen, anthracyclines and their combinations, showing
      response rates of 25.5%, 22.0% and 29.6% respectively, suggesting that this agent
      is also effective on breast carcinomas which were insensitive to tamoxifen and
      anthracyclines. For efficacy classified in terms of metastatic lesions, the
      response rate was significantly higher in soft tissues than in other involved
      organs, and the response rate of bone metastasis was limited. Bone marrow
      suppression, including leukopenia and thrombocytopenia, was thought to be the
      dose-limiting toxicity of KM2210. Genital bleeding due to the released estrogen
      was observed as a characteristic side effect. KM2210 is considered to be useful
      for the treatment of advanced and recurrent breast cancer when administered at a
      dose level of 200 mg per day for more than 4 weeks.

PMID- 8135469
TI  - Aminoglutethimide in advanced breast cancer: prospective, randomized comparison
      of two dose levels. Italian Cooperative Group.
AB  - In a multicenter randomized clinical trial 106 post-menopausal patients with
      progressive metastatic breast cancer were allocated to receive 500 mg or 1000 mg
      Aminoglutethimide (AG) per os daily. Cortisone Acetate (CA) replacement dose was
      37.5 mg/day orally in both groups. In 91 fully evaluable patients, no
      statistically significant difference was observed between the two therapeutic
      regimens, neither in terms of overall response (28 vs 35%) and by site responses,
      nor in terms of median time to progression (10.5 vs 14.5 months) and median
      overall survival (20 vs. 22 months). The tolerability was satisfactory in both
      regimens. Although no statistically significant differences occurred, in the low
      dose regimen we observed fewer patients with side-effects (25% vs 6%) and induced
      grade 3 side-effects (4% vs 9%). Our results confirm that AG daily doses of 500
      and 1000 mg associated with corticosteroids have a comparable effect. Because of
      its slight but clinically noticeable better tolerability, the lower dose is the
      preferable regimen in the treatment of advanced breast cancer.

PMID- 8135470
TI  - Triptorelin (D-Trp-6-LHRH) in combination with carboplatin-containing
      polychemotherapy for advanced ovarian cancer: a pilot study.
AB  - In experimental and clinical phase II trials GnRH agonists were shown to possess
      antitumor activity in ovarian cancer. The outcome of prostatic cancer was also
      improved experimentally by a combination of cytostatic chemotherapy and GnRH
      analogs. Encouraged by these results, we administered micro-encapsulated
      triptorelin (Decapeptyl CR), 3.75 mg on the first day of each chemotherapy
      course, to 15 patients with advanced ovarian cancer in addition to adjuvant,
      carboplatin-containing chemotherapy (Carboplatin, Epirubicin, Prednimustine and
      Carboplatin, Etoposide) after radical surgery. Patients received a total of 6
      courses. After the completion of combined chemotherapy GnRH analogs were
      continued for another 6 months at 28-day intervals. Results were compared with
      those obtained in a group of 15 ovarian cancer patients receiving the same
      chemotherapy regimen without GnRH medication. At a median follow-up of 36 months
      no significant differences were seen in terms of response, survival and time to
      progression. However, patients undergoing chemotherapy+triptorelin tended to show
      a more positive outcome than those on chemotherapy alone. G1 and G2 tumors in
      particular were found to respond better to the combined treatment regimen.

PMID- 8135471
TI  - The clinical importance of DNA synthesis and aneuploidy in bone and soft tissue
      tumours.
AB  - DNA flow cytometric analysis including the analysis of S-phase fraction was
      performed on 46 bone and soft tissue tumours. Histologically, 24 lesions were
      benign, 11 were low grade and 11 were high grade malignant tumours. The
      percentages of aneuploidy in these groups were 29, 54 and 82, respectively. The S
      phase fraction was smaller than 14% in all benign tumours. High S-phase fraction
      (> or = 14%) was found in 3 out of 11 low-grade tumours (27%) and in 9 out 11
      high-grade tumours (82%). Seven of nine patients who died of metastatic disease
      during the average 5 year follow-up had aneuploid stemlines with S-phase fraction
      higher than 14%. Histologically, these were all high-grade tumours. Three
      patients with high S-phase in low-grade tumours survived. We conclude that high
      DNA synthetic activity in an aneuploid population, more than the DNA aneuploidy
      alone, has prognostic significance in musculoskeletal tumours.

PMID- 8135472
TI  - Phase I trial of erbulozole (R55104).
AB  - Erbulozole (R55 104) is a water soluble congener of the microtubule inhibitor
      tubulozole, which has proven to possess anti-invasive, antitumoral and
      radiosensitizing capacities. A dose-finding study was performed on respectively 9
      patients (every three weeks; doses ranging from 20 mg/m2 to 100 mg/m2; maximum 2
      cycles per patient) and 6 patients (weekly; doses ranging from 20 mg/m2 to 50
      mg/m2; maximum 60 cycles per patient). At all dosages, hematological and
      biochemical toxicity was very limited. Seven patients complained of pain at the
      tumor site (grade I to III). Dose limiting toxicity appeared at respectively 100
      mg/m2 (one administration every three weeks) and 50 mg/m2 (weekly
      administration). At this level, 2 patients displayed a dose-limiting Wernicke's
      encephalopathy-like syndrome. Other secondary effects were headache, fever,
      exacerbation of dyspnea and moderate nausea and vomiting.

PMID- 8135473
TI  - Expression of tumour associated antigens 12H12, 2E11, 7A9, CEA and DF3 in human
      breast cancer.
AB  - Expression of tumour associated antigens 12H12, 2E11, 7A9, CEA and DF3 was
      determined immunohistochemically in paraffin embedded biopsy specimens from 42
      breast carcinomas. The mean (SD) of staining index (I) for 12H12 was 0.95(0.94),
      for 2E11 1.30(0.99), for FA9 1.11(0.92), for CEA 0.03(0.1) and for DF3
      1.32(0.93). Of the 42 carcinomas, 3 (7.1%) were totally negative for 12H12, 3/42
      (7.1%) for 2E11, 6/42 (14.3%) for 7A9, 34/42 (81%) for CEA and 6/45 (13.3%) for
      DF3. The 12H12 positivity was related significantly to axillary lymph node status
      (r = 0.41, p < 0.01), expression of 7A9 (r = 0.71, p < 0.001), expression of 2E11
      (r = 0.76, p < 0.001), expression of DF3 (r = 0.40, p < 0.01) and TPA serum level
      (r = 0.41, p < 0.01). The 2E11 positivity was related to axillary lymph node
      status (r = 0.43, p < 0.01), expression of 7A9 (r = 0.95, p < 0.001) and 12H12 (r
      = 0.76, p < 0.001). The 7A9 positivity was related to axillary lymph node status
      (r = 0.44, p < 0.01), expression of 7A9 (r = 0.71, p < 0.001), 12H12 (r = 0.71, p
      < 0.001) and 2E11 (r = 0.95, p < 0.001). The DF3 positivity was significantly
      related to expression of 12H12 (r = 0.40, p < 0.01). The CEA positivity was not
      significantly related to any of the tested variables. The results suggest that
      antigens 12H12, 2E11 and 7A9 should be subject to further analysis in breast
      cancer research. Particularly, they may be helpful in separating benign breast
      lesions from the more malignant ones. Secondly, the relationship between high
      expression of the antigens and axillary lymph node status suggests that these
      antigens may have also prognostic value.

PMID- 8135474
TI  - Five primary cancers in one patient.
AB  - We report a 62-year-old man with five primary cancers. He underwent nephrectomy
      for a right renal cell carcinoma and removal of malignant meningioma and 6 years
      later was diagnosed as having a rectal cancer and hepatocellular carcinoma. He
      died of respiratory failure and a gastric cancer was found at autopsy.

PMID- 8135475
TI  - Correlation between positive CA 72-4 serum levels and lymph node involvement in
      patients with gastric carcinoma.
AB  - CA 72-4 serum marker has been shown to be one of the most specific and sensitive
      markers for monitoring gastric cancer. In the present study we evaluated the
      correlation between CA 72-4, CA 19-9 and CEA serum levels, and tumor size and
      lymph node involvement in gastric carcinoma patients. One-hundred sixty-one
      patients with primary or recurrent gastric carcinoma were studied. Elevated CA 72
      4, CA 19-9, and CEA serum levels were found in 42.2%, 32.3% and 24.2%,
      respectively. As previously shown, the combination of CA 72-4 and CA 19-9
      increased positive samples to 56.5%, while the addition of CEA did not further
      improve this percentage. Unlike what has been previously published, none of the
      markers showed a significant correlation with serosal involvement. In fact,
      elevated serum levels were observed for the three markers in a very low
      percentage of cases either in T1-T2N0 or T3-T4N0 patients. In contrast, CA 72-4
      showed a highly significant correlation with lymph node involvement: T1-T4N0
      patients had positive CA 72-4 levels in 5 out of 37 (13.5%), while T1-T4N1 in 12
      out of 32 (37.5%), and T1-T4N2 in 20 out of 40 (50%) (p < 0.003). CA 19-9 and CEA
      serum levels were not significantly correlated. Since the presence of lymph node
      metastases is considered a negative prognostic factor, these results suggest that
      the measurement of CA 72-4 serum levels may be an important parameter in the
      diagnosis and clinical follow-up of patients with gastric carcinoma.

PMID- 8135476
TI  - Interrelation between Western type cancers and non-Western type cancers as
      regards their risk variations in time and space. VI. Chronological transition of
      various cancer risks of the world from 1975 to 1985.
AB  - We comparatively investigated the age-adjusted incidence rates (AAIRs) of overall
      cancers of the world between 1975 and 1985 to see whether or not any consistent
      change is in progress in the risk for cancer in general on a world scale. Results
      obtained are summarized as follows: 1) the total male population of the world,
      but not the total female population, experienced a significant rise in AAIR for
      cancers of all sites during the above 10 years. 2) In the comparison study of
      geographical subgroups, the above integral cancer risk significantly increased
      with time in the male population of Canada, USA-White, USA-Black, European
      continent (EC)-West, EC-others and Great Britain, and also in the female
      populations of both USA-Black and Great Britain. In other geographical subgroups
      the cancer risks for 1985 were also higher than those for 1975, but the
      differences were not statistically significant. 3) The above increase of cancer
      risk in general was accounted for by a surplus in weight of the increasing
      contribution of Western-type cancers over the decreasing contribution of non
      Western type cancers to the integral cancer risk of a population. 4) Japan was
      found to be an exceptional case in that the risk for liver cancer (a non-Western
      type cancer) increased 3 to 8 fold from 1975 to 1985 in both male and female
      populations of Japan. Evidence was presented to suggest that the above increase
      of liver cancer incidence could be related to the persistence of social tension
      following the first oil crisis in 1973. In summary, the chronological transition
      patterns of cancer risk in Japan as well as in other parts of the world support
      our interpretation that social tension linked to the economic recession plays a
      crucial role in the production of recent changes of cancer risk in the world.

PMID- 8135477
TI  - p53 protein expression in squamocellular carcinomas of the lip.
AB  - Twenty-six cases of squamocellular carcinomas of the lip were immunostained for
      p53 protein. Nuclear accumulation of p53 protein was observed in 88% of the 26
      carcinomas, in 64% of adjacent "normal" epithelium and in all four cases with
      adjacent atypical squamous epithelium. 93% of the specimens (13/14) with p53
      protein accumulation in "normal" epithelium demonstrated evidence of solar
      elastosis. UV radiation may induce p53 gene mutation as an early event in the
      neoplastic transformation.

PMID- 8135478
TI  - Enhanced inhibition of thymidylate synthase by 5-fluorouracil and [6S]leucovorin
      combination therapy for breast cancer.
AB  - The influence of the addition of [6S]leucovorin (LV) to 5-fluorouracil (5-FU)
      preoperative chemotherapy was examined in patients with surgically resectable
      breast cancer who had had no prior treatment. The patients underwent one of the
      following three treatments at their will: (1) 5-FU 500 mg/m2 administered by an
      i.v. bolus; (2) [6S]LV 250 mg/m2 infused intravenously over two hours, with 5-FU
      500 mg/m2 as an IV bolus at the midpoint of [6S]LV infusion, (3) no drug
      treatment. Tumors were resected 24 hours after the dose of 5-FU with or without
      [6S]LV. These studies confirmed an increased stabilization of 5
      fluorodeoxyuridine monophosphate (FdUMP)-thymidylate synthase(TS)-folate ternary
      complex with the addition of [6S]LV. An increase of total TS activity was also
      found.

PMID- 8135479
TI  - p53 protein expression in mammary and extramammary Paget's disease.
AB  - p53 is a tumour-suppressor gene, mutations of which are found in malignant skin
      lesions. We studied the immunohistochemical expression of the (mutated) p53
      protein in 17 cases of Paget's disease (12 mammary and 5 extramammary). Four of
      the mammary specimens (33.3%) expressed p53 within Paget's cells; in one of these
      an underlying ductal adenocarcinoma was present and this was also p53-positive.
      All extramammary cases proved p53-negative. These results underline the
      differences that exist between mammary and extramammary Paget's disease and
      favour the origin of the former from the underlying adenocarcinoma rather than
      the surface epithelium.

PMID- 8135480
TI  - Immunocytochemical determination of estrogen and progesterone receptors and flow
      cytometric DNA analysis of breast cancer on fine needle aspirates.
AB  - A prospective study was performed on a series of 42 patients with breast
      carcinoma. Immunocytochemical determination of receptors for estrogens (ER) and
      progesterone (PR) and flow cytometric DNA analysis (DNA-ploidy and the S-phase
      fraction) were performed on material obtained from fine-needle aspirates (FNA).
      The patients underwent subsequent surgery, and the same parameters were
      determined on the surgical samples. The correlation between the biochemical and
      the immunocytochemical methods gave for ER, r = 0.853, p < 10 (-6) and for PR, r
      = 0.830, p < 1.6 (-6). In addition, comparisons of FNA's with the surgical
      samples showed significant relationships for the DNA index (r = 0.96, p <
      0.000001) and for the S-phase fraction (r = 0.88, p < 0.000001).

PMID- 8135481
TI  - Value of ascitic fluid ferritin in the differential diagnosis of malignant
      ascites.
AB  - The ascitic fluid ferritin concentrations were compared with serum-ascites
      albumin gradient (SAAG), in their diagnostic ability for detection of malignancy
      in 60 patients with ascites: 29 with chronic liver disease alone (CLD) and 31
      patients with various neoplasms. Of the patients with malignancy, 12 had liver
      metastases, 9 had no evidence of liver involvement, and 10 had hepatocellular
      carcinoma (HCC) with or without coexisting liver cirrhosis. Analysis of our data
      confirms that the ascitic ferritin is a more accurate indicator of malignant
      ascites (MA) than the SAAG. This new parameter is particularly helpful in
      distinguishing MA associated with HCC and/or metastatic liver disease from
      nonmalignant ascites due to CLD alone.

PMID- 8135482
TI  - Low doses of interleukin-2 can cure large bovine ocular squamous cell carcinoma.
AB  - Four cows bearing large Ocular Squamous Cell Carcinomas (BOSCC) were treated by
      10 intratumoral injections (Monday-Friday for 2 consecutive weeks) of 200,000 U
      Interleukin-2 (Cetus). Tumors regressed in 2 out of 4 cases. This result shows
      that even large tumors may regress after local IL-2 treatment.

PMID- 8135483
TI  - A combined chemo-endocrine treatment with tegafur, adriamycin, methotrexate and
      tamoxifen for advanced renal cell carcinoma.
AB  - Eight patients with advanced renal cell carcinoma were given a new chemo
      endocrine treatment with tegafur, adriamycin, methotrexate and tamoxifen.
      Estrogen receptor was detected in five cases from renal or metastatic tumors. The
      patients were medicated with 800-1, 200mg of tegafur and 20 mg of tamoxifen daily
      po and 20mg of adriamycin and 10 mg of methotrexate iv intermittently at two week
      intervals. Two patients were regarded as CR, two as PR, one as NC and three as
      PD. Two out of three with estrogen receptor and one out of two without estrogen
      receptor responded favorably to this treatment. Side effects observed during the
      treatment were Grade II nausea/vomiting in six, Grade II leukopenia in three,
      Grade I thrombocytopenia in two, and Grade I hepatoxicity in three patients. The
      patients were found to be enjoying a good quality of life during the treatment
      because of lowered toxicity. This treatment can be regarded as a good treatment
      modality for advanced renal cell carcinoma.

PMID- 8135484
TI  - Different site mutation of the K-ras gene in a patient with metachronous double
      lung cancers.
AB  - We present a case with metachronous double lung cancers proved by molecular
      analysis. A male patient first had lung cancer discovered when he was 67 years
      old, and a second lung cancer was found when he was 71 years old. Pathologically,
      the first cancer was moderately to well differentiated adenocarcinoma and the
      second cancer was well differentiated adenocarcinoma. These findings suggested
      that the second cancer was not metastasis from the first lung cancer but a second
      primary lung cancer. According to the PCR and oligonucleotide mutation specific
      dot blot hybridization, the first lung cancer had a GGT to GTT mutation, while
      the second lung cancer had a GGT to TGT mutation at codon 12 of the K-ras gene.
      These results thus prove that these tumors were metachronous double cancers.

PMID- 8135485
TI  - Suramin and serum insulin-like growth factor levels in metastatic cancer
      patients.
AB  - Suramin, a polysulphonated naphthylurea, inhibits the activity of several growth
      factors in in vitro experiments and clinical responses have been reported in
      human solid tumors. We decided to investigate the relationship between suramin
      treatment and serum levels of insulin-like growth factor I (IGF-I) and II (IGF
      II) in advanced breast, prostate and lung cancer patients. The serum IGF-I, IGF
      II levels were determined by radioimmunoassay. A significant decline of IGF-I and
      IGF-II serum levels was demonstrated in suramin treated patients. Our results
      suggest that suramin-induced IGF suppression could be one of the possible
      mechanisms of suramin action.

PMID- 8135486
TI  - Adriamycin, cyclophosphamide and vindesine (ACV) versus mitoxantrone,
      cyclophosphamide and vindesine (NCV) in advanced breast cancer.
AB  - The choice of chemotherapy for advanced breast cancer patients is based on both
      response rates and anticipated side effects. Two polychemotherapy regimens, ACV
      and NCV, were compared in an open study with 90 patients of whom 69 were
      evaluable both for efficacy and toxicity. Both ACV and NCV are active in
      metastatic breast cancer. ACV leads to more remissions in a relatively short
      time. NCV treatment results in a larger proportion of stable diseases. ACV causes
      more important alopecia, nausea and vomiting. NCV gives more anemia. The
      characteristics of both treatment results give the oncologist the opportunity to
      choose in particular clinical situations.

PMID- 8135487
TI  - Carcinosarcoma and separate neuroendocrine malignant tumor of a malignancy
      promoter, the gastric stump.
AB  - We report a case of carcinosarcoma and separate neuroendocrine malignant tumor of
      the gastric stump. The case is interesting because of its unique pathological
      features and it confirms the role of the gastric stump as a very important
      "malignancy promoter".

PMID- 8135488
TI  - Prognostic significance of estrogen receptor expression in ovarian cancer.
      Immunoreactive Score (IRS) vs. Composition Adjusted Receptor Level (CARL).
AB  - An Immunoreactive Score (IRS) was compared to the Composition Adjusted Receptor
      Level (CARL) evaluating prognostic significance of estrogen receptor (ER)
      expression in 61 ovarian cancers after > or = 8 years. CARL of ER allowed for
      calculating individual risk curves in stage III and IV, Grade 2 and 3, serous
      ovarian carcinoma after surgical debulking to < or = 2 cm residual and platinum
      based chemotherapy. In overall analysis and in subsets defined by tumor stage,
      grade or a combination thereof significant prognostic distinction became possible
      using a cutoff IRS of 4 vs. 0 or vs. scores < or = 3. This study substantiates ER
      as a prognostic variable in human ovarian cancer and for the first time
      establishes the value of an IRS.

PMID- 8135489
TI  - Intraperitoneal administration of cisplatin and etoposide during surgery for
      patients with gastric cancer.
AB  - Intraperitoneal chemotherapy has been attempted to treat peritoneal seeding in
      patients with gastric cancer. In this study, 13 patients with far advanced
      gastric cancer were given a complex chemotherapy regimen, cisplatin and
      etoposide, intraperitoneally during surgery. Cisplatin and etoposide was given
      100 mg/body (58-90 mg/m2) and 200 mg/body (115-180 mg/m2), respectively, before
      closing the abdominal wall. There was one operative death who had an unresectable
      gastric cancer and died due to respiratory insufficiency, probably related to the
      drugs. There were no critical side effects due to the drugs among patients who
      underwent gastrectomy. Postoperative complications encountered were 2 cases of
      leukopenia, 2 of vomiting, 2 of renal impairment and 1 of liver dysfunction.
      These complications were transient and limited. The median survival duration was
      7.0 months in this study. Thus, intraperitoneal cisplatin and etoposide should be
      examined for clinical use in larger scale trials.

PMID- 8135490
TI  - Biochemical modulation of chemotherapy and radiotherapy in head and neck cancer.
AB  - In order to improve the treatment of advanced H&N cancer we must consider to
      adopt new strategies as: new/better cytostatic agents; new combinations of
      present cytostatic agents and; potentiation of radiotherapy and cytostatic agents
      by biochemical modulation, which we define as potentiation of therapy by non
      chemotherapeutic agents. The list of agents that can potentiate chemotherapy or
      circumvene resistance is comprehensive. Most of the data are derived from in
      vitro studies. Much attention has been given to the fact that calcium channel
      blocker (CCB) agents can circumvene the multi-drug resistance (MDR) phenotype.
      Cisplatin, 5-fluorouracil, bleomycin and methotrexate, used in the treatment of
      head and neck cancer, are not part of the MDR phenotype. Still there are a few
      interesting reports indicating that CCB's could enhanced the antitumour actions
      of cisplatin, and that this interaction may be: (a) very specific; (b) unique to
      each species of CCB and (c) is independent of their binding affinity and
      classical function as inhibitors of the voltage sensitive calcium channels.
      Metoclopramide (MCA) is a structural analogue of procainamide used worldwide for
      preventing nausea and vomiting. It has structural resemblance to some of the
      known inhibitors of the DNA associated enzyme poly ADPRT such as benzamide.
      Benzamide is however rather toxic. MCA has been shown to enhance the effect of
      CDDP in vivo as well as in permeabilized cells in vitro, indicating that the DNA
      damaging effect of MCA is not dependent on cytoplasmatic enzymes or messenger
      systems. Radiobiologists have pointed out important biologic characteristics
      about tumour tissue such as hypoxia in relation to tumour radiosensitivity.
      Nicotinamide can effect tumour radiosensitivity in vivo. Comparing the response
      of mice in skin and tumour under different gas breathing regimens, a considerable
      therapeutic gain has been demonstrated for oxygen and carbon dioxide (95% O2 + 5%
      CO2) breathing mice. The effect of ionizing radiation (RT) on xenografted
      squamous cell carcinoma can also be enhanced by MCA. The optimal treatment
      interval is MCA given one hour before RT, which is in concordance with the
      hypothesis that MCA has to be present at the site of injury when RT is given in
      order to interact with repair mechanisms. We could not in conventional mice
      detect any MCA induced enhancement of either acute skin reaction or in LD50/30
      after whole body irradiation, which indicates a potential therapeutic gain using
      MCA in a clinical setting. The above discussed interactions between biochemical
      modulators and chemo-/radio-therapeutic agents serve to illustrate the fruitful
      concept of biochemical potentiation of cytotoxicity.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8135491
TI  - Immune defects in patients with head and neck cancer.
AB  - Any deficiency or suppression of the immune response in head and neck cancer
      patients might be due to genetic factors of the host (patient factors), to tumor
      antigens (tumor factors) or to the medical treatment such as irradiation,
      anesthesia, major surgery or cytokine therapy (treatment factors). In order to
      achieve an effective adjuvant immunotherapy a thorough analysis of the immune
      situation is a prerequisite. With the increasing knowledge of the fine
      interactions with the immune system, the armamentarium has increased over the
      years. At the beginning only skin testing and T- and B-cell numbers were
      analyzed, whereas today a correlation of cell numbers, distribution and function
      is feasible.

PMID- 8135492
TI  - Oncogene regulation by growth factors.
AB  - Complementary studies on quite different eukaryotic systems are revealing that
      certain mitogenically important enzymes, that were previously assigned to
      unrelated metabolic pathways, bind and may be regulated by receptor tyrosine
      kinases (RTKs). A deeper understanding of the relationships between these
      signalling pathways promises to improve our attempts to rationalise important
      properties of the transformed phenotype, such as tumour growth rates, metastasis
      and mechanisms of cellular transformation, and thereby, it is hoped, improve
      prognostic, diagnostic and treatment regimes. This review briefly summarises
      results from our and other laboratories that have shed light on specific
      intracellular signalling enzymes that respond to stimulation by RTKs.

PMID- 8135493
TI  - Perspectives of monoclonal antibodies for detection and treatment of head and
      neck tumours.
AB  - Monoclonal antibodies (mabs) are potentially powerful tools for the detection and
      treatment of cancer. To date, only a limited number of mabs are available to head
      and neck cancer. We produced 5 different groups of mabs to head and neck cancer.
      These mabs were characterized for their reactivity tumour and non-tumour tissues.
      Furthermore, biochemical elucidation of recognized antigens was provided. In
      animal studies the effectiveness of mabs for diagnoses and therapy of cancer is
      clearly demonstrated. The first results of a clinical study for the detection of
      head and neck cancer with mabs are shown. Finally, the future of mabs in clinical
      oncology is discussed.

PMID- 8135494
TI  - Oncogenes related to head and neck cancer.
AB  - Cancer has been defined as a fundamental disorder of cellular growth control.
      Which arises in some cells through changes in genes (DNA-level:
      geneamplification, mutation and rearrangement) or their expression (RNA- and
      protein-level), and gives these cells a growth advantage in comparison to the
      surrounding cells. Since the last decade we know the identity of these genes and
      the nature of the changes they underwent in the cancer cell. Only a few of the
      known oncogenes play a role in head and neck cancer. These are the EGFR
      (epidermal growth factor receptor), c-myc, the ras gene family, int-2, hst- 1 and
      bcl- 1. In some clinical disorders, like childhood neuroblastoma and breast
      cancer, oncogenes play already an important role in tumor staging as well as a
      prognostic parameter. The aim for the future is the therapeutic application of
      oncogenes better known as gene therapy.

PMID- 8135495
TI  - Nonrandom chromosome aberrations and clonal populations in head and neck cancer.
AB  - Losses of 3p13-p24, 5q12-q23, 8p22-p23, 9p21-p24, 10p13-pter, 18q22-q23, and
      21q11.2-q21 (40-60% of tumors); loss of the inactive X and loss (or
      rearrangement) of Y in 70% of tumors from female and male patients respectively;
      and gains of 2 to 5 extra copies of 3q21-qter, 5p14-pter, 7p13-p22, 8q13-q24.3,
      and 11q13-q23, (30-40% of tumors) are the most common chromosome abnormalities in
      head and neck squamous cell carcinomas (SCCs). SCCs are monoclonal and cell lines
      derived from separate surgeries in the same patient contain closely related
      subclones. Analysis of subclones within tumors provides clues to the sequence of
      karyotypic changes. Chromosome hotspots such as loss of distal 18q and gains
      affecting 11q13-11q21 are likely to contain genes important in the development
      and progression of SCC.

PMID- 8135496
TI  - Peripheral blood stem cells in children with solid tumors. Part II.
      Immunocytologic detection of tumor cells in bone marrow and peripheral blood stem
      cell harvests.
AB  - Simultaneous comparative assessment of tumor contamination in bone marrow
      aspirates and peripheral blood stem cell collections using immunocytochemical
      techniques was done in 6 children with neuroectodermal tumors. In 3 neuroblastoma
      patients tumor cells were detected in 5 of 16 marrow samples but not in
      peripheral blood stem cells. Clonogenic tumor cell reinfusion in the autologous
      support setting may be avoided in neuroblastoma patients by using peripheral
      blood stem cells.

PMID- 8135497
TI  - C-peptide pattern in patients with pancreatic cancer.
AB  - The pathogenetic mechanism underlying glucose intolerance in pancreatic cancer is
      still unclear. We studied the pattern of three glucose regulating hormones (C
      peptide, glucagon and GH) in pancreatic cancer patients with (N = 34) and without
      (N = 8) hyperglycemia, and compared the findings made with those from subjects
      with other hyperglycemic conditions of well-known origin [type I diabetes
      mellitus (8 cases) and diabetes mellitus secondary to chronic pancreatitis (13
      cases) or liver cirrhosis (4 cases)]. In hyperglycemic pancreatic cancer
      patients, C-peptide was absent in 26% of the cases, reduced in 24%, elevated in
      29% and within the normal range in the remaining 21%. In normoglycemic pancreatic
      cancer this hormone was reduced in two cases (25%) and within the normal range in
      all the others. GH was within the normal range in all cases: glucagon was below
      the normal range in some hyperglycemic pancreatic cancer patients (41%) or within
      the normal range in all the remaining patients. No correlations were found
      between the three hormones when findings from subjects were considered all
      together. However, in pancreatic cancer C-peptide and glucagon presented
      consensual variations. C-peptide, glucagon and GH levels were not related to
      tumor volume; glucagon was found to be associated with liver metastases. C
      peptide was correlated with serum ALT and ALP. We may conclude that hyperglycemia
      associated with pancreatic cancer may be caused by different mechanisms. In some
      cases a reduced secretion of both insulin and glucagon was observed, as occurs in
      chronic pancreatitis. In the majority of patients, beta cell function appears
      normal, and the hyperglycemic state may depend on an altered peripheral
      sensitivity to insulin due to the pancreatic pathology itself or to consensual
      liver involvement.

PMID- 8135498
TI  - Screening results in a family cancer clinic: five years experience.
AB  - We present our experience so far of screening individuals referred to the Cancer
      family clinic at St. Mark's Hospital from 1986, with the results of the follow-up
      of these individuals. 651 individuals from 436 families were offered colonoscopic
      surveillance at five-yearly intervals. The median age at which the examination
      was performed was 41 years. Families were subdivided according to family history;
      15.8% conformed to the Amsterdam criteria for hereditary nonpolyposis colorectal
      cancer (HNPCC). The pathological findings were correlated with the type of
      pedigree; abnormalities were more often found in males than females (30% of
      colonoscopies in males revealed adenomas, and 17% in females), and adenoma
      prevalence increased with age. Adenoma prevalence (27% v.s. 21% at all ages, and
      38% v.s. 25% in individuals over the age of 35y.), multiple adenomas and the
      proportion of proximally sited adenomas were all higher in HNPCC families;
      however, dysplasia and villous or large adenomas were not more common in
      individuals from HNPCC families. Four of the 7 carcinoma detected were in HNPCC
      families (3% v.s. 0.6%).

PMID- 8135499
TI  - Sixty years of onchocerciasis vector control: a chronological summary with
      comments on eradication, reinvasion, and insecticide resistance.

PMID- 8135500
TI  - Metamorphosis behavior of flies.

PMID- 8135501
TI  - Risks from natural versus synthetic insecticides.

PMID- 8135502
TI  - Neuropsychological assessment.

PMID- 8135503
TI  - Health psychology: why do some people get sick and some stay well?

PMID- 8135504
TI  - Cognitive approaches to emotion and emotional disorders.

PMID- 8135505
TI  - Images of the mind: studies with modern imaging techniques.

PMID- 8135506
TI  - Sexual differentiation of the human nervous system.

PMID- 8135507
TI  - Chemical senses.
AB  - In the last decade, studies using approaches from molecular biology have
      substantially advanced our understanding of the early events in olfaction and
      taste. The many odorants that we can recognize may well interact with many
      distinct receptor proteins. Of the four taste qualities that we recognize,
      studies on salty and sour suggest that these tastes involve ion channels in the
      membrane of receptor cells while sweets and bitters bind to receptor proteins.
      Some volatiles (pheromones) play special roles in reproductive behavior via the
      vomeronasal organ (VNO) and the accessory olfactory system. Initial belief that
      humans lack a VNO has been questioned recently, thus raising the fascinating
      possibility of human pheromones. The roles that taste and smell play in the world
      of the newborn are very different. Acceptance of sweet and rejection of bitter
      appear to be hard-wired while the affect associated with odors depends much more
      on experience. Genetic variation may produce total losses (Kallman's syndrome
      produces anosmia and familial dysautonomia produces ageusia) or losses specific
      to certain stimuli. The best known of the specific anosmias is that for
      androstenone, which has no smell to some, a urinous smell to others, and a smell
      like sandalwood to still others. Analogous to the specific anosmias, some
      individuals are unable to taste PROP while others, supertasters, perceive PROP to
      be exceedingly bitter. Clinical studies reveal pathologies responsible for total
      or partial losses. The olfactory system, dependent on one cranial nerve, is more
      vulnerable than taste, and total anosmia is a relatively common clinical problem.
      Three cranial nerves carry taste and two of those nerves inhibit one another such
      that damage to one disinhibits the other and preserves over-all taste function.
      Total ageusia is very rare. Throughout these studies we see that taste and
      olfaction have different properties and often different functions (e.g. odor and
      reproduction). Yet taste and smell can also be integrated to determine what does
      or does not enter the body. In Adrian's words, "we are dealing with the sense
      organs which signal the quality of the air we breathe and that of the food and
      drink we propose to swallow."

PMID- 8135508
TI  - Color appearance: on seeing red--or yellow, or green, or blue.

PMID- 8135509
TI  - Language specificity and elasticity: brain and clinical syndrome studies.

PMID- 8135510
TI  - Comparative sensitivity of the echovirus type 25 JV-4 prototype strain and two
      recent isolates to glutaraldehyde at low concentrations.
AB  - The sensitivity of two recently isolated antigenic variants of echovirus type 25
      (Montpellier 76-1262 and Thionville 86-222) to glutaraldehyde (GTA) at low
      concentrations was compared with that of the JV-4 prototype strain. The purified
      viruses were treated under the same conditions with GTA at concentrations ranging
      from 0.002 to 0.10%. The wild strains exhibited significantly lower sensitivity
      to GTA than did the prototype strain; with 0.10% GTA, a 2 log10 unit reduction
      was obtained in 5 min for JV-4 and in 60 and 80 min for Montpellier 76-1262 and
      Thionville 86-222, respectively. A comparison with previous results obtained with
      poliovirus type 1 showed that the inactivation rates of echovirus type 25 wild
      strains were fivefold lower than those of the poliovirus type 1 Sabin strain. The
      comparative electrophoretic and immunoblot analyses showed differences in the
      results of GTA binding with capsid proteins of the viruses. Unlike in the
      poliovirus type 1 Mahoney strain and in the echovirus type 25 JV-4 reference
      strain, GTA produced only minor intermolecular cross-linkings in the viral
      particles of the two wild strains of echovirus type 25. Our results suggest that
      there are both intertypic and intratypic differences in the GTA sensitivities of
      enterovirus strains. They are of relevance to disinfection procedures in
      digestive endoscopy and to the choice of the enterovirus strain used for
      evaluating the efficacy of disinfectants.

PMID- 8135511
TI  - Sphinganase, a new endoglycanase that cleaves specific members of the gellan
      family of polysaccharides.
AB  - A sporeforming gram-positive aerobic bacterium was isolated from soil and shown
      to secrete an endoglycanase that cleaves the tetrasaccharide backbone structure
      of specific members within the gellan family of related bacterial
      exopolysaccharides. We refer to these polysaccharides as sphingans. The
      structures of the sphingans differ by the type and position of side groups that
      are attached to the backbone. The new enzyme named sphinganase degrades welan,
      gellan, deacylated gellan, and polysaccharides S-88, S-7, and S-198. However, the
      enzyme does not attack rhamsan or polysaccharide NW11. Methods for growing the
      bacteria, isolating the enzyme, and assaying sphinganase activity are presented,
      and uses for the enzyme are proposed.

PMID- 8135512
TI  - Effect of microwave radiation on inactivation of Clostridium sporogenes (PA 3679)
      spores.
AB  - Three techniques for studying effects of microwave radiation on microorganisms
      were introduced. Spores of Clostridium sporogenes (PA 3679) were chosen as a test
      organism because the kinetic parameters for thermal inactivation are well known
      and because of the importance of the genus Clostridium to the food industry. For
      the first technique, a specially designed kinetics vessel was used to compare
      inactivation rates of microwave-heated and conventionally heated spores at steady
      state temperatures of 90, 100, and 110 degrees C. Rates were found to be similar
      at the 95% confidence level. The second and third techniques were designed to
      study the effect of relatively high power microwave exposure at sublethal
      temperatures. In the second approach, the suspension was continuously cooled via
      direct contact with a copper cooling coil in a well-mixed vessel, outside the
      microwave oven. The suspension was pumped through a Teflon loop in the oven,
      where it continuously absorbed approximately 400 W of microwave power.
      Inactivation occurred in both irradiated and unirradiated samples. It was
      suspected that copper ions entered the suspension from the copper coil and were
      toxic to the spores. The fact that the results were similar, however, implied the
      absence of nonthermal microwave effects. In the third approach, the copper coil
      was replaced with a silicone tubing loop in a microwave transparent vessel. The
      suspension was continuously irradiated at 150 W of microwave power. No detectable
      inactivation occurred. Results indicated that the effect of microwave energy on
      viability of spores was indistinguishable from the effect of conventional
      heating.

PMID- 8135513
TI  - Evidence for phage-mediated gene transfer among Pseudomonas aeruginosa strains on
      the phylloplane.
AB  - As the use of genetically engineered microorganisms for agricultural tasks
      becomes more frequent, the ability of bacteria to exchange genetic material in
      the agricultural setting must be assessed. Transduction (bacterial virus-mediated
      horizontal gene transfer) is a potentially important mechanism of gene transfer
      in natural environments. This study investigated the potential of plant leaves to
      act as surfaces on which transduction can take place among microorganisms.
      Pseudomonas aeruginosa and its generalized transducing bacteriophage F116 were
      used as a model system. The application of P. aeruginosa lysogens of F116 to
      plant leaves resulted in genetic exchange among donor and recipient organisms
      resident on the same plant. Transduction was also observed when these bacterial
      strains were inoculated onto adjacent plants and contact was made possible
      through high-density planting.

PMID- 8135514
TI  - Engineering and production of streptokinase in a Bacillus subtilis expression
      secretion system.
AB  - Streptokinase is one of the major blood-clot-dissolving agents used in many
      medical treatments. With the cloned streptokinase gene (skc) available,
      production of the secreted streptokinase from various Bacillus subtilis strains
      was studied. The use of the six-extracellular-protease-deficient strain, WB600,
      greatly improved the production yield of the secreted streptokinase. A modified
      skc which has the original skc promoter and signal sequence replaced with the B.
      subtilis levansucrase promoter and signal sequence was also constructed. B.
      subtilis carrying either the wild-type or the modified skc produces streptokinase
      at a comparable level. Even with WB600 as the expression host, a C-terminally
      processed streptokinase was also observed. Through region-specific combinatorial
      mutagenesis around the C-terminal processing sites, streptokinase derivatives
      resistant to C-terminal degradation were engineered. One of the derivatives
      showed a 2.5-fold increase in specific activity and would potentially be a better
      thrombolytic agent.

PMID- 8135515
TI  - Classification of the uptake hydrogenase-positive (Hup+) bean rhizobia as
      Rhizobium tropici.
AB  - Phenotypic and genetic characterization indicated that Hup+ bean rhizobial
      strains are type IIA and type IIB Rhizobium tropici. The Hup+ strain USDA 2840,
      which did not cluster with either of the two types of R. tropici in a restriction
      fragment length polymorphism analysis, had electrophoretic patterns of PCR
      products generated with primers for repetitive extragenic palindromic and
      enterobacterial repetitive intergeneric consensus sequences similar to those of
      three reference strains of R. tropici type IIA. The Hup+ strain USDA 2738, which
      clustered with the reference strain of R. tropici IIB in a restriction fragment
      length polymorphism analysis, had electrophoretic patterns of PCR products
      generated with primers for repetitive extragenic palindromic and enterobacterial
      repetitive intergeneric consensus sequences more closely resembling those of the
      reference strains of R. tropici type IIA than those of type IIB. DNA
      amplification with the Y1 and Y2 primers to generate a portion of the 16S rDNA
      operon was useful to distinguish R. tropici type IIA strains from other bean
      rhizobial strains. The phylogenetic position of the type IIA strain of R. tropici
      USDA 2840, determined from the partial 16S rDNA sequence, indicated a more
      distant relationship with the type IIB strain of R. tropici CIAT899 than with the
      as yet unnamed rhizobial species of Leucaena leucocephala, TAL 1145. Therefore,
      we suggest that it may be appropriate either to separate R. tropici types IIA and
      IIB into two different species or to identify TAL 1145 to the species level as a
      third type of R. tropici.

PMID- 8135516
TI  - Purification and characterization of NADP-specific alcohol dehydrogenase and
      glutamate dehydrogenase from the hyperthermophilic archaeon Thermococcus
      litoralis.
AB  - Thermococcus litoralis is a strictly anaerobic archaeon that grows at
      temperatures up to 98 degrees C by fermenting peptides. Little is known about the
      primary metabolic pathways of this organism and, in particular, the role of
      enzymes that are dependent on thermolabile nicotinamide nucleotides. In this
      paper we show that the cytoplasmic fraction of cell extracts contained NADP
      specific glutamate dehydrogenase (GDH) and NADP-specific alcohol dehydrogenase
      (ADH) activities, neither of which utilized NAD as a cofactor. The GDH is
      composed of identical subunits having an M(r) of 45,000 and had an optimal pH and
      optimal temperature for glutamate oxidation of 8.0 and > 95 degrees C,
      respectively. Potassium phosphate (60 mM), KCl (300 mM), and NaCl (300 mM) each
      stimulated the rate of glutamate oxidation activity between two- and threefold.
      For glutamate oxidation the apparent Km values at 80 degrees C for glutamate and
      NADP were 0.22 and 0.029 mM, respectively, and for 2-ketoglutarate reduction the
      apparent Km values for 2-ketoglutarate, NADPH, and NH4+ were 0.16, 0.14, and 0.63
      mM, respectively. This enzyme is the first NADP-specific GDH purified form a
      hyperthermophilic organism. T. litoralis ADH is a tetrameric protein composed of
      identical subunits having an M(r) of 48,000; the optimal pH and optimal
      temperature for ethanol oxidation were 8.8 and 80 degrees C, respectively. In
      contrast to GDH activity, potassium phosphate (60 mM), KCl (0.1 M), and NaCl (0.3
      M) inhibited ADH activity, whereas (NH4)2SO4 (0.1 M) had a slight stimulating
      effect. This enzyme exhibited broad substrate specificity for primary alcohols,
      but secondary alcohols were not oxidized.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135517
TI  - Use of the Escherichia coli beta-glucuronidase (gusA) gene as a reporter gene for
      analyzing promoters in lactic acid bacteria.
AB  - A transcriptional fusion vector, designated pNZ272, based on the promoterless
      beta-glucuronidase gene (gusA) of Escherichia coli as a reporter gene, has been
      constructed for lactic acid bacteria. The replicon of pNZ272 was derived from the
      Lactococcus lactis plasmid pSH71, allowing replication in a wide range of gram
      positive bacteria and E. coli. The applicability of pNZ272 and the expression of
      the gusA gene in L. lactis was demonstrated in shotgun cloning experiments with
      lactococcal chromosomal and bacteriophage DNA. In addition, three defined
      lactococcal promoters were inserted in pNZ272: the plasmid-derived lacA promoter,
      the chromosomal usp45 promoter, and a promoter from bacteriophage phi SK11G. The
      three resulting plasmids showed beta-glucuronidase activity in a gusA-deficient
      E. coli strain and in four species of lactic acid bacteria belonging to the
      genera Lactobacillus, Lactococcus, and Leuconostoc. The copy numbers of the gusA
      expressing plasmids were similar within a single species of lactic acid bacteria.
      However, the specific beta-glucuronidase activity and the gusA mRNA levels varied
      considerably both within a single species and among different species of lactic
      acid bacteria. The transcriptional start site of all three promoters was
      determined and found to be identical in the different species. The results of
      this comparative promoter analysis indicate that the requirements for efficient
      transcription initiation differ among the lactic acid bacteria studied.

PMID- 8135518
TI  - Cloning and targeted gene disruption of EXG1, encoding exo-beta 1, 3-glucanase,
      in the phytopathogenic fungus Cochliobolus carbonum.
AB  - The phytopathogenic fungus Cochliobolus carbonum produces an extracellular enzyme
      capable of degrading beta 1,3-glucan in an exolytic manner. On the basis of
      partial amino acid sequences of the purified enzyme, two degenerate
      oligonucleotides were synthesized and used as PCR primers to amplify a 1.1-kb
      fragment of corresponding genomic DNA. The PCR product was used to isolate the
      genomic copy of the gene, called EXG1. Partial sequencing of the genomic DNA
      confirmed that the PCR product corresponded to EXG1. A strain of the fungus
      specifically mutated in the EXG1 gene was constructed by homologous integration
      of an internal fragment of EXG1. In the mutant, enzymatic activity and the
      corresponding peak of UV absorption during high-pressure liquid chromatography
      purification were reduced by at least 98%. However, crude culture filtrates of
      the mutant retained 44% of the wild-type beta 1,3-glucanase activity. This
      residual activity was due to two additional activities which were
      chromatographically separable from the product of EXG1 and which were coeluted
      with beta 1,3-beta 1,4-glucanase activity. Growth of the EXG1 mutant was normal
      on sucrose and oat bran but was reduced by 65% on pure beta 1,3-glucan. The EXG1
      mutant was still pathogenic to maize.

PMID- 8135519
TI  - Manganese peroxidases of the white rot fungus Phanerochaete sordida.
AB  - The ligninolytic enzymes produced by the white rot fungus Phanerochaete sordida
      in liquid culture were studied. Only manganese peroxidase (MnP) activity could be
      detected in the supernatant liquid of the cultures. Lignin peroxidase (LiP) and
      laccase activities were not detected under a variety of different culture
      conditions. The highest MnP activity levels were obtained in nitrogen-limited
      cultures grown under an oxygen atmosphere. The enzyme was induced by Mn(II). The
      initial pH of the culture medium did not significantly affect the MnP production.
      Three MnP isozymes were identified (MnPI, MnPII, and MnPIII) and purified to
      homogeneity by anion-exchange chromatography followed by hydrophobic
      chromatography. The isozymes are glycoproteins with approximately the same
      molecular mass (around 45 kDa) but have different pIs. The pIs are 5.3, 4.2, and
      3.3 for MnPI, MnPII, and MnPIII, respectively. The three isozymes are active in
      the same range of pHs (pHs 3.0 to 6.0) and have optimal pHs between 4.5 and 5.0.
      Their amino-terminal sequences, although highly similar, were distinct,
      suggesting that each is the product of a separate gene.

PMID- 8135520
TI  - Bacterial succession in necrotic tissue of agria cactus (Stenocereus gummosus).
AB  - The bacterial communities associated with the development of necroses in injured
      agria cactus tissue were examined in the field by using both human-induced
      injuries and cactus tissue inoculated with cactophilic bacteria. Whole-cell
      bacterial fatty acids were used to determine when and where each of 23 detected
      species occurred. This information was then used to describe successional
      patterns of bacterial colonization. Although the number of bacterial species in
      human-induced injuries reached a maximum on day 16, the Shannon-Weaver diversity
      index increased to a plateau, which reflects a stable bacterial community. The
      potential of the bacterial community to macerate the injured cactus tissue was
      also examined, and the results indicate that the bacteria initially colonizing
      the newly injured cactus tissue were more likely to contain pectinolytic,
      proteolytic, and lipolytic enzymes than were the bacteria entering the injuries
      once tissue maceration had already begun. The cactophilic fruit fly Drosophila
      mojavensis has been previously shown to carry bacteria to newly injured cactus
      tissue. In these studies, exclusion of these insects did not significantly affect
      bacterial succession or community structure. This supports our contention that
      bacteria colonize injured tissue primarily by passive transport, e.g., on wind
      blown particles.

PMID- 8135522
TI  - Evaluation of a commercial enzyme immunoassay kit (RIDASCREEN) for detection of
      staphylococcal enterotoxins A, B, C, D, and E in foods.
AB  - The RIDASCREEN SET kit (R-Biopharm GmbH, Darmstadt, Germany), a commercial
      staphylococcal enterotoxin (SE) visual immunoassay kit, was evaluated for its
      efficacy. The kit utilizes monovalent capture antibodies against SE types A to E
      (SEA to SEE); therefore, it simultaneously detects and identifies the enterotoxin
      types. The major advantages of the kit are (i) a high degree of specificity
      (except for naturally occurring peroxidases, food compositions or ingredients and
      microbiological products due to growth of nonstaphylococcal microorganisms did
      not cause false-positive results; additionally, no cross-reactions among reagents
      of the kits were observed), (ii) excellent sensitivity (minimum detectable limits
      were 0.20 to 0.30 ng of SEs per ml of extracts of ham, salami, and mushroom and
      0.30 to 0.35 ng of SEs per ml of cheese extracts, or 0.50 to 0.75 ng of SEs per g
      of foods such as noodles, ham, salami, cheese, and turkey), (iii) simplicity (the
      kit enabled direct assay of SEs in food extracts without the need for lengthy
      extraction or concentration procedures), (iv) rapidity (it took less than 3 h to
      complete the analysis of individual enterotoxin types SEA to SEE), and (v) its
      semiquantitative results (optical density values could be read against a standard
      curve to estimate the amount of SE in the extract). The RIDASCREEN kit is a
      convenient, rapid, and reliable tool for the detection and identification of SEs
      in foods.

PMID- 8135521
TI  - The alcohol dehydrogenase gene adh1 is induced in Aspergillus flavus grown on
      medium conducive to aflatoxin biosynthesis.
AB  - An Aspergillus flavus cDNA library was screened by differential hybridization to
      isolate clones corresponding to genes that are actively transcribed under culture
      conditions conducive to aflatoxin biosynthesis. One clone with a 1.28-kb insert
      was isolated, and its nucleotide sequence was determined. The nucleotide sequence
      of this clone had 75% DNA identity to those of the alcohol dehydrogenase genes
      from Aspergillus nidulans, and the putative polypeptide translated from the cDNA
      sequence had 82% similarity with the amino acid sequences of the A. nidulans
      proteins. Thus, this gene has been designated adh1. Southern hybridization
      analysis of genomic DNA from A. flavus indicated that there was one copy of the
      adh1 gene. Northern (RNA) hybridization analysis indicated that the adh1
      transcript accumulated in culture medium conducive to aflatoxin production and
      the timing of accumulation of adh1 transcripts was similar to that for aflatoxin.
      Fusion of the promoter region of adh1 to a beta-glucuronidase reporter gene
      indicated that accumulation of the adh1 transcript was the result of
      transcriptional activation. These molecular data support previous physiological
      evidence that showed the importance of carbohydrate metabolism during aflatoxin
      biosynthesis.

PMID- 8135523
TI  - Monoclonal antibody-based enzyme-linked immunosorbent assay of Fusarium T-2 and
      zearalenone toxins in cereals.
AB  - Direct, competitive enzyme-linked immunosorbent assays (ELISAs) with monoclonal
      antibodies have been developed for quantitative determination of trichothecene T
      2 toxin (T-2), and zearalenone (F-2) from different cereals: Among the several
      extraction solvents tried, 89% acetonitrile with additives was chosen. The
      extracts were then used without cleanup in the ELISA. With appropriate dilution
      of the samples (1:25 or 1:50), the matrix effects caused by lipid and/or protein
      content of the samples can be diminished to the extent that the assay is no
      longer impaired. The mean recoveries from cereals infected with 100 to 2,000 ng
      of T-2 and 50 to 500 ng of F-2 per g were 85 and 91%, respectively. The measuring
      range of the T-2 test is 100 to 2,000 ng/g, and that of the F-2 test is 25 to 400
      ng/g. The mean within-assay and interassay coefficients of variation of standard
      curves are both less than 10%. According to recovery results with artificially
      infected cereals, our tests proved to be suitable for rapid screening of food and
      feed samples for the presence of T-2 and F-2 toxins.

PMID- 8135524
TI  - Recognition of chimeric small-subunit ribosomal DNAs composed of genes from
      uncultivated microorganisms.
AB  - When PCR was used to recover small-subunit (SSU) rRNA genes from a hot spring
      cyanobacterial mat community, chimeric SSU rRNA sequences which exhibited little
      or no secondary structural abnormality were recovered. They were revealed as
      chimeras of SSU rRNA genes of uncultivated species through separate phylogenetic
      analysis of short sequence domains.

PMID- 8135525
TI  - Evaluation of Rambach agar for detection of Salmonella subspecies I to VI.
AB  - Salmonella strains belonging to subspecies I to VI were investigated for colony
      color when grown on Rambach agar. Most strains of Salmonella subspecies I, II,
      IV, and VI behaved as described. All strains of Salmonella subspecies IIIa, IIIb,
      and V produced beta-D-galactosidase and blue-green colonies which could not be
      distinguished in color from Escherichia coli and other lactose-fermenting members
      of the family Enterobacteriaceae.

PMID- 8135526
TI  - Staphylococcin 1580 is identical to the lantibiotic epidermin: implications for
      the nature of bacteriocins from gram-positive bacteria.
AB  - Staphylococcin 1580 was purified to homogeneity from culture supernatants of
      Staphylococcus epidermidis 1580 by means of adsorption to XAD 2, cation exchange
      chromatography, and high-performance liquid chromatography on reversed-phase C18.
      The purified active substance migrated in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis with an apparent M(r) of approximately 2,000. Amino acid
      analysis, mass determination (2,165 Da) and N-terminal sequencing (Ile-Ala-Xaa
      Lys-Phe-Ile-Xaa-Xaa-Pro-Gly-Xaa-Ala-Lys-block) demonstrated that staphylococcin
      1580 is identical to epidermin, a lanthionine-containing antibiotic peptide
      (lantibiotic).

PMID- 8135527
TI  - Increased fertility of Corynebacterium glutamicum recipients in intergeneric
      matings with Escherichia coli after stress exposure.
AB  - Corynebacterial recipient cells exposed to heat, organic solvents, pH shifts, or
      detergents show an increased fertility in subsequent interspecific matings with
      Escherichia coli. This effect is independent of de novo protein biosynthesis and
      seems to be due to a direct inactivation of a restriction system active against
      foreign DNA that enters the cell by IncP-mediated conjugation.

PMID- 8135528
TI  - The nonactivated estrogen receptor (naER) of the goat uterus is a tyrosine
      kinase.
AB  - The nonactivated estrogen receptor (naER) has been isolated and purified to
      absolute homogeneity from the goat uterine cytosol. It is a 66-kDa protein,
      sedimenting at 4.2 S on linear sucrose density gradients and having a Stokes
      radius of 36 A. It displays high affinity and specificity for estradiol and
      diethyl stilbestrol with a Kd of 1 x 10(-10) M. CNBr peptide analysis reveals
      that it has a primary structure distinctly different from that of the regular
      estrogen receptor even though anti-ER antibody cross-reacts with the nonactivated
      ER. The protein gains access to the DNA only upon dimerization with the estrogen
      receptor activation factor (E-RAF), a DNA-binding protein having no capacity to
      bind estradiol. Analysis reveals that both naER and E-RAF are protein kinases.
      While the E-RAF is a serine kinase, naER functions as a tyrosine kinase. No
      protein kinase activity is displayed by the regular estrogen receptor. The
      protein kinase activity of the naER is inhibited in the presence of estradiol.
      Similarly, the protein kinase activities associated with the proteins disappear
      when the naER and E-RAF are brought together.

PMID- 8135529
TI  - A DNA-binding (R-I) and a non-DNA-binding (R-II) estrogen receptor in the goat
      uterine nucleus: purification and characterization.
AB  - Two forms of nuclear estrogen receptors have been isolated and purified from the
      goat uterus. The biochemical characteristics of the proteins imply that the
      receptors may be identified as the type I and type II nuclear estrogen receptors.
      Nevertheless, we felt a necessity to exercise caution in using this nomenclature
      and, therefore, decided to identify them instead as R-I and R-II, respectively.
      While R-I is the DNA-binding form, R-II is a non-DNA-binding protein. The two
      proteins are totally dissimilar in other physical characteristics like the Stokes
      radii (36 A for R-I and 21 A for R-II), sedimentation coefficients (4.8 S for R-I
      and 3.8 S for R-II), the Kd (1 nM for R-I and 2 nM for R-II), and the nature of
      the CNBr fragmentation of the proteins. The two proteins, however, cross-react
      with polyclonal antibodies raised against goat uterine estrogen receptor
      activation factor (E-RAF), a DNA-binding protein with no capacity to bind
      estradiol, originally discovered by T.N.R.V. Thampan and J. H. Clark (1981,
      Nature 290, 152-154). A major feature of the R-II isolation procedure is the
      chromatography of the protein on a heat shock protein 90-Sepharose column in the
      presence of molybdate ions and elution using a molybdate-free buffer. While
      estradiol-17 beta (E2) binding to R-II was inhibited by the presence of
      dithiothreitol and quercetin in the medium, E2-R-I interaction remained
      unaffected by these exposures.

PMID- 8135530
TI  - Reduction of HDL- and LDL-associated cholesterylester and phospholipid
      hydroperoxides by phospholipid hydroperoxide glutathione peroxidase and Ebselen
      (PZ 51).
AB  - The reaction of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and
      Ebselen with phospholipid and cholesterylester hydroperoxides associated with
      HDLox and LDLox was investigated using specific HPLC assays for the
      hydroperoxides of phosphatidylcholine (PCOOH) and cholesteryllinolate (Ch18:2
      OOH) and for cholesteryllinolate hydroxides (Ch18:2-OH). HDLox and LDLox were
      formed from the corresponding isolated native lipoproteins by controlled and
      limited oxidation initiated by aqueous peroxyl radicals. Incubation of HDLox or
      LDLox in the presence of PHGPx/GSH or Ebselen/GSH resulted in rapid degradation
      of both classes of lipid hydroperoxides, with equimolar amounts of Ch18:2-OH
      formed from Ch18:2-OOH. No pronounced differences were observed between PCOOH and
      Ch18:2-OOH in terms of substrate specificity, whereas HDLox-associated PCOOH and
      Ch18:2-OOH appeared to be slightly better substrates for PHGPx/GSH as compared to
      those in LDLox. Also, Ch18:2-OOH associated with HDLox but not LDLox were reduced
      by Ebselen or GSH alone. These in vitro findings indicate that the enzymatic
      PHGPx/GSH and the nonenzymatic Ebselen/GSH systems can efficiently reduce
      hydroperoxides of phospholipids and cholesterylesters associated with intact
      lipoproteins.

PMID- 8135531
TI  - The pH-dependent behavior of catalytic activities of Azospirillum brasilense
      glutamate synthase and iodoacetamide modification of the enzyme provide evidence
      for a catalytic Cys-His ion pair.
AB  - The pH dependence of the kinetic parameters of the glutamine- and ammonia
      dependent reactions of Azospirillum brasilense glutamate synthase revealed the
      presence of ionizable groups with pKa values between 6 and 10 involved in the
      binding of the substrates and in catalytic steps. The V profile of the glutamine
      dependent reaction is complicated by a deviation from a simple bell-shaped curve
      between pH 8 and pH 10, which may suggest that deprotonation of a group with pKa
      value in this region decreases but does not abolish glutamine-dependent enzyme
      activity. This group does not seem to be required in the ammonia-dependent
      reaction of GltS, which decreases on the acidic and alkaline sides as groups with
      pKa values of about 8.8 and 9.9 dissociate. The V/K profile for ammonia exhibits
      a single pKa value of about 8.7, suggesting that ammonia is the actual substrate
      of the enzyme, and that ammonia binding to glutamate synthase is largely pH
      independent. The hypothesis that a group with pKa between 8 and 10 is involved in
      the glutaminase segment of the glutamine-dependent glutamate synthase activity
      was supported by studies of the modification of the enzyme by 6-diazo-5-oxo-L
      norleucine, a glutamine analog, and iodoacetamide, a cysteine-directed reagent.
      Analyses of the kinetics of inactivation of the enzyme in the presence and
      absence of enzyme substrates and their analogs at different pH values
      demonstrated that iodoacetamide reacts with a group involved in glutamine binding
      and/or activation, most likely the cysteine residue at the N-terminus of
      glutamate synthase alpha subunit, which may form a Cys-His ion pair in the active
      site of glutamate synthase, as suggested for other amidotransferases (Mei, B.,
      and Zalkin, H. (1989) J. Biol. Chem. 264, 16613-16619).

PMID- 8135532
TI  - Resonance energy transfer determination of the distance between the four cysteine
      364 residues in Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase.
AB  - Each of the four subunits of the Saccharomyces cerevisiae phosphoenolpyruvate
      carboxykinase has one cysteine residue (Cys-364) that is protected against
      alkylation by MnATP and that is thought to be located at (or close to) the active
      site (M. Alvear, M. V. Encinas, S. Latshaw, R. G. Kemp, and E. Cardemil, 1992,
      Biochim. Biophys. Acta 1119, 35-38). To determine the distance relationships
      between these residues within this tetrameric enzyme, we have derivatized one of
      these reactive thiols with N-acetyl-N'-(5-sulfo-1-naphthyl) ethylenediamine
      (AEDANS) and the others progressively with 4-[N-[(acetoxy)ethyl]-N-methylamino]-7
      nitrobenz-2-oxa-1,3-diazole (ANBD). In the doubly labeled protein nonradiative
      singlet-singlet energy transfer between AEDANS (donor) and ANBD (acceptor) was
      observed. The efficiency of the energy transfer is proportional to the number of
      occupied acceptor sites. From these data it has been determined that one of the
      acceptor sites is 33 A from the donor, and the remaining two sites are 44-46 A
      from the donor. Cross-linking experiments revealed that mainly cross-linked
      dimers were produced upon reaction of the enzyme with o-phthalaldehyde and
      dithiobissuccinimidylpropionate. We interpret these results as an indication that
      this tetrameric enzyme is most likely composed of an association of two dimers.

PMID- 8135533
TI  - Extracellular glutathione peroxidase mRNA and protein in human cell lines.
AB  - Extracellular glutathione peroxidase (E-GPx) and cellular glutathione peroxidase
      (C-GPx) are selenoenzymes encoded by two distinct genes. Using specific
      immunoprecipitations of [75Se]selenium metabolically labeled human cell lines in
      culture, it was found that Caco-2, Hep3B, Hep G2, and Caki-2 synthesize C-GPx and
      E-GPx and secrete E-GPx. HBL-100, BT-20, and MCF-7 synthesize only C-GPx. The
      relationship between Se status (as determined by C-GPx activity) and E-GPx and C
      GPx mRNA steady-state levels was investigated in Hep G2, Caco-2, and Caki-2. The
      most Se-deficient Hep G2, Caco-2, and Caki-2 cells had 8.7 +/- 2.6, 11.2 +/- 4.9,
      and 9.4 +/- 5.0%, respectively, of C-GPx activity of the replete cells. The
      steady-state levels of mRNA were measured by Northern and slot blot hybridization
      analysis. By Northern analysis, a single band was present at 1.0 and 1.80 kb for
      C-GPx and E-GPx mRNA, respectively, in all three cell lines. Scanning
      densitometry of the blots revealed that the most Se-deficient cells had 30-50% C
      GPx mRNA and 60-80% E-GPx mRNA of the replete cells. It is concluded that, in
      addition to previously examined human cell lines, Hep3B and Caco-2 make and
      secrete E-GPx while HBL-100 and BT-20 do not. The slightly reduced levels of G
      GPx and E-GPx mRNA in Se-deficient human cell lines can only partially account
      for the decreased C-GPx activity in Se-deficient human cell lines.

PMID- 8135534
TI  - Stress-induced insolubilization of certain proteins in ascites tumor cells.
AB  - The stress-induced redistribution of cellular proteins between Triton (X-100)
      soluble and Triton-insoluble fractions was studied in EL-4 thymoma and Ehrlich
      carcinoma cells. It was shown by electrophoresis and immunoblotting that a common
      sign of the cells which in vitro underwent such different harmful influences as
      ATP depletion, heat shock, oxidative stress, and SH reagent treatment was
      significant insolubilization of actin and 70-kDa heat-shock protein (hsp70). At
      the same time, each type of injury caused the specific insolubilization of some
      major cellular proteins. The transient ATP deprivation alone (without protein
      denaturation) induced a rapid insolubilization of myosin that was the earliest
      manifestation of ATP deficiency in the cells. Thermal stress without sharp
      decrease in ATP level induced a transition of 90-kDa heat-shock protein (hsp90)
      and 47-kDa polypeptide in Triton-insoluble fraction. The insolubilization of
      myosin and 47- and 35-kDa proteins was typical for the cells subjected to
      oxidative stress or SH reagent treatment, both of which caused damage of cellular
      proteins as well as ATP loss. The redistribution of the above proteins was
      intrinsic in the stressed cells of either ascites cell line, allowing one to
      consider it as characteristic and stress-specific cellular response to various
      injuries.

PMID- 8135535
TI  - Importance of the modulation of glycolysis in the control of lactate metabolism
      by fatty acids in isolated hepatocytes from fed rats.
AB  - In liver cells from fed rats, lactate utilization depends on its extracellular
      concentration and the threshold concentration at which lactate uptake
      equilibrates release is about 3 mM. Even-chain fatty acids (butyrate, octanoate,
      or oleate) played a crucial role (i) to depress the lactate release, from 40%
      (butyrate or oleate) to 72% (octanoate), and (ii) to lower the threshold
      concentration for lactate utilization (down to 1 mM with octanoate). The effects
      of fatty acids were connected to their inhibition of hepatic glycolysis,
      estimated by the detritiation of [6-3H]glucose (about -30% with butyrate or
      oleate and -45% with octanoate). Fatty acids depressed the cellular concentration
      of pyruvate which, at physiological concentration of lactate, favors its
      utilization. The rise in ketone bodies concentration in response to fatty acids
      reflected an enhanced acetyl CoA production, resulting in an accumulation of
      citrate. In parallel there was a drop of the cellular concentration of fructose
      2,6-biphosphate. As a result, there was an inhibition of the flux through 6
      phosphofructo-1 kinase (50, 75, or 40% inhibition with butyrate, octanoate, or
      oleate, respectively). The other regulatory glycolysis steps, catalyzed by
      glucokinase and pyruvate kinase, were not affected by fatty acids. Inhibition of
      hepatic glycolysis by fatty acids seems connected to acetyl-CoA generation since
      octanoate, readily metabolized to acetyl-CoA and ketone bodies by hepatocytes,
      had a more potent stimulatory effect on the hepatic uptake of lactate than
      butyrate or oleate. Propionate, which yields practically no acetyl CoA, slightly
      stimulated lactate release and elevated the threshold of lactate utilization. The
      present data suggest thus that, in hepatocytes from fed rats, fatty acids
      effectively inhibit glycolysis and switch liver cell metabolism toward
      gluconeogenic conditions, which promotes lactate utilization.

PMID- 8135536
TI  - Comparative sugar degradation by (OH). produced by the iron-driven Fenton
      reaction and gamma radiolysis.
AB  - We compared the attack of deoxyribose and mannitol by (OH). produced by gamma
      radiolysis or the iron-driven Fenton reaction. Deoxyribose (DR) oxidation by
      gamma radiolysis gave rise to thiobarbituric reactive substances (TBARS) with a
      yield of 17 mol (OH). per mole of TBARS. (OH). scavengers (benzoate, formate, and
      pentoxifylline) protected DR from oxidation. Mannitol was similarly oxidized by
      (OH). produced by gamma radiolysis, with a yield of 14 mol (OH). per mole of
      TBARS produced. A mixture containing both DR and mannitol gave rise to TBARS
      production with a yield of 9 mol (OH). per mole of TBARS superior to that of each
      product separately, suggesting the formation of secondary radicals responsible
      for the degradation of DR or mannitol. When (OH). was produced by the iron-driven
      Fenton reaction, DR gave rise to TBARS whereas mannitol did not. Furthermore,
      mannitol protected DR against degradation, apparently in the same way as
      desferrioxamine and diethylenetriaminepentaacetic acid, suggesting that it acts
      as an iron chelator. It can thus be assumed that, according to the site of (OH).
      production, sugar molecules are degraded as a function of their rate constant
      with (OH). or their iron chelating capacity.

PMID- 8135537
TI  - Chemical modification of human UDP-glucuronosyltransferase UGT1*6 by diethyl
      pyrocarbonate: possible involvement of a histidine residue in the catalytic
      process.
AB  - Chemical modification with diethyl pyrocarbonate (DEPC) of the recombinant human
      liver UDP-glucuronosyltransferase UGT1*6 in enriched membrane fractions from a
      V79 cell line resulted in a rapid inactivation of the glucuronidation reaction,
      measured with 4-methyl-umbelliferone as aglycone substrate, with a second-order
      rate constant of 3110 M-1.min-1 at pH 6.0 and 25 degrees C. The enzymatic
      activity was restored by hydroxylamine. Chemical modification with 0.2 mM DEPC
      for 60 s decreased the apparent Vmax 2.4-fold without significantly affecting the
      apparent Km toward 4-methylumbelliferone and UDP-glucuronic acid. Similarly, the
      binding of the photoactivatable cosubstrate analog [beta-32P]5-azido-UDP
      glucuronic acid to the active site was not affected by the chemical modification.
      The enzyme was protected against this inactivation by 4-methylumbelliferone,
      suggesting that the modified residue was located in or near the aglycone binding
      site. In contrast, the cosubstrate UDP-glucuronic acid potentiated the
      irreversible inhibition, indicating a conformational change in the protein upon
      binding. The pH-dependence of the inactivation was in agreement with the
      modification of an amino acid residue with a pKa of 6.1. On the other hand,
      analysis of the variation of Vmax and Vmax/Km values of the glucuronidation
      reaction as a function of the pH revealed the presence of two essential residues
      with a pKa within the range 5.7-6.0. The data of the chemical modification of the
      recombinant enzyme together with that of the pH dependence of the activity
      strongly suggest the involvement of a histidine residue, highly reactive toward
      DEPC, which could be the base catalyst of the glucuronidation reaction supported
      by human UGT1*6.

PMID- 8135538
TI  - Identification of the lipid moiety and further characterization of the novel
      lipophosphoglycan-like glycoconjugates of Trichomonas vaginalis and Trichomonas
      foetus.
AB  - The lipid moiety of the lipophosphoglycan (LPG)-like glycoconjugates of
      Trichomonas vaginalis and Trichomonas foetus, parasites of the urogenital tract
      of human and cattle, respectively, has been isolated and characterized by a
      combination of enzymatic and chemical degradation, chromatography, and mass
      spectrometry. The carbohydrate composition of the glycan inositol lipid core is
      also reported. The glycan inositol core of trichomonad glycoconjugates is unique
      in having more than one GlcN and is significantly larger than any other glycan
      core reported so far. T. vaginalis glycoconjugate binds strongly to the lectin
      RCA-I, which suggest that the macromolecule possesses terminal beta 1,4-linked
      galactosyl residues. The binding of T. foetus glycoconjugate to the lectin UEA-I
      suggests the presence of terminal alpha 1,2-linked fucose. Acid hydrolysis of
      deaminated and reduced LPG products yields a [3H]anhydromannitol-containing
      product, indicating the presence of unacetylated glucosamine in the trichomonad
      LPGs. Reductive radiomethylation has been applied to label free amino groups in
      the hexosamine or other free amine-containing residues of the trichomonad
      glycoconjugates. Treatment of the LPGs with phosphatidylinositol-specific
      phospholipase C from Bacillus thuringiensis liberates a ceramide substituent.
      Treatment of LPGs with nitrous acid releases a phospholipid moiety containing myo
      inositol and ceramide, implying that the LPGs are anchored in the membrane via an
      inositol-phosphate-ceramide. Structural characterization of the ceramide by gas
      liquid chromatography (GC) and GC-mass spectrometry indicated the presence of the
      major long-chain base sphinganine (d 18: 0 dihydrosphingosine) and a C 16:0 N
      acyl group. Lipophosphoglycans from both parasites contain ceramide as their only
      lipid moiety. These results suggest that T. vaginalis and T. foetus anchor their
      LPG-like glycoconjugates on the cell surface via inositol-phosphoceramide and
      also the glycan inositol core of the macromolecule appears to be unique in
      nature.

PMID- 8135539
TI  - The NAD kinase: a phosphoryltransferase displaying an oxido-reductase activity-
      an electrophoretic study.
AB  - The search for a valuable technique for rapid detection, after electrophoresis,
      of the activity of various NAD kinase isoforms possibly present in different
      plant materials, has revealed interesting peculiarities of this enzyme (EC
      2.7.1.23; also called ATP:NAD+ 2'-phosphotransferase). At first and in the unique
      but obligatory presence of NAD, the NAD kinase acts almost instantaneously as an
      oxido-reductase (probably coupled with the transformation of NAD to NADH). In the
      additional presence of ATP, the transformation of NAD+ to NADP+ reinforced such
      an oxido-reductase activity. Final assays testing for the specificity of the
      phosphoryl donor revealed that not only ATP but also GTP, G6P, and even NADP
      could be the substrate; the efficiencies of these phosphoryl donors varied with
      the different isoforms of NAD kinase, evidenced in the different seeds tested,
      and compared with NAD kinase from heterotropically grown Euglena cells, and NAD
      kinase purified from chicken liver (from Sigma Chemical Co.).

PMID- 8135540
TI  - The effects of fur on the transcriptional and post-transcriptional regulation of
      MnSOD gene (sodA) in Escherichia coli.
AB  - Earlier studies have shown that the Fur (ferric uptake regulation) protein acts
      as an anaerobic/aerobic repressor of MnSOD (sodA) expression. We found that the
      aerobic expression of sodA::lacZ fusion in a Fur- background to be threefold
      higher than in a Fur+ background. This effect of fur mutation was not seen in a
      strain harboring the sodA+ gene instead of the sodA::lacZ fusion. However, we
      observed a proportionate increase in the concentrations of sodA::lacZ and sodA+
      mRNAs in response to a mutation in the fur gene. These data suggest that the
      formation of active MnSOD is dependent on a functional fur gene. Indeed, we found
      that in a fur mutant iron was incorporated into SodA in place of manganese, thus
      creating inactive and/or partially active forms of the enzyme (i.e., Fe2SodA
      and/or Mn,FeSodA, respectively), resulting in little or no increase in total
      MnSOD activity. Thus, Fur plays the role of a repressor at the transcriptional
      level, but it also plays an indirect role at the post-transcriptional level where
      it affects the maturation of SodA into a fully active enzyme, Mn2SodA (MnSOD).

PMID- 8135541
TI  - Purification and properties of porcine liver ornithine transcarbamylase.
AB  - Ornithine transcarbamylase (OTCase) has been purified from porcine liver by a
      simple four-step procedure that included chromatography on an affinity column to
      which the transition-state analogue, delta-N-phosphonacetyl-L-ornithine (PALO),
      was covalently bound. The procedures employed yielded an enzyme which was
      purified some 260-fold and was judged to be homogeneous by nondenaturing- and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Apparent
      homogeneity of the enzyme was confirmed by N-terminal sequence analysis. The
      molecular weight of the porcine enzyme was determined by Sephadex gel exclusion
      chromatography and sedimentation equilibrium. An approximate molecular weight of
      107,000 was calculated by both procedures. The single band obtained by SDS-PAGE
      indicated a subunit molecular weight of 36,800 +/- 700; hence, the enzyme is a
      trimer of identical subunits. The sedimentation coefficient of the native enzyme
      was determined to be 6.47. At pH 8.0, the Km values for the substrates are 0.41
      and 1.3 mM for ornithine and carbamyl phosphate, respectively. PALO is a
      competitive inhibitor and has a Ki of 0.13 microM, which suggests that it binds
      with about 10,000 times greater affinity than carbamyl phosphate. Amino acid
      analysis performed on acid hydrolyzed enzyme yielded 323 amino acids per monomer.
      Performic acid oxidation of the enzyme, followed by acid hydrolysis and amino
      acid analysis, showed three cysteine residues per subunit. A partial specific
      volume of 0.725 cc/g was calculated from the amino acid composition. Reaction of
      purified porcine OTCase with phenylglyoxal, an arginine-specific reagent, results
      in complete loss of catalytic activity. The decrease in enzymatic activity
      correlates with the modification of 1 mol of arginine per mole of OTCase monomer.
      In the presence of 20 mM carbamyl phosphate, 93% of the activity is retained
      during a 1-h reaction time. Other substrates and substrate combinations offer
      less protection.

PMID- 8135542
TI  - Steady-state kinetics of glutamine cyclotransferase.
AB  - The reaction mechanism of papaya latex glutamine cyclotransferase was studied
      using pH and temperature dependencies, a proton inventory technique, and
      molecular modeling. The pH-dependence of the Michaelis-Menten parameters showed
      that the published pH dependence of the enzyme "activity" was mainly the result
      of pH-dependent change of the active (unprotonated) substrate concentration. The
      enzyme activity as such changed very slightly in the pH range between 4.5 and 10.
      The solvent kinetic isotope effect reflected a change in Vm while the proton
      inventory was found to be linear with the fractionation factor of the
      exchangeable proton in the transition state of 0.785. The results were not
      consistent with an acyl-enzyme mechanism, but rather favored a simple
      intramolecular cyclization of the glutamine residue to the pyroglutamic acid
      residue. The mechanism proposed consists of the following main steps: (i)
      intramolecular nucleophilic attack on the gamma-C = O carbon by the nitrogen of
      the alpha-amino group, (ii) transfer of a proton from the alpha-amino group to
      the nitrogen of the amide group, facilitated by an acidic group of the enzyme,
      and (iii) expulsion of the ammonia-leaving group promoted by this or another
      acidic enzyme group.

PMID- 8135543
TI  - The effect of hemoglobin, hematin, and iron on neutrophil inactivation in
      superoxide generating systems.
AB  - When Escherichia coli was incubated with xanthine oxidase and acetaldehyde, the
      killing of E. coli was accelerated by iron-EDTA but inhibited by hematin or
      hemoglobin. On the other hand, when E. coli was incubated with human neutrophils
      in the presence of phorbol myristate acetate (PMA), all of these iron species at
      concentrations of a few micromolar accelerated the inactivation of neutrophils
      and in so doing protected the E. coli from being killed by the neutrophils. The
      inactivation of the neutrophils was accompanied by an increase in lipid
      peroxidation and by a decrease in viability measured with trypan blue. This
      inactivation was inhibited by scavengers such as deoxyribose, mannitol, or
      thiourea. Desferrioxamine B and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) both
      inhibited the inactivation mediated by iron-EDTA, but had no effect on the
      hematin- or hemoglobin-mediated inactivation. Vanadium (vanadyl ion), an
      effective Fenton reagent, behaved in the same way as iron-EDTA relative to the
      effects of DMPO on neutrophil inactivation. These results led us to conclude that
      neutrophils were inactivated during PMA stimulation by OH radicals in the
      presence of iron-EDTA and by some other oxidizing species when hematin or Hb is
      present. Ascorbate enhanced the inactivation of neutrophils mediated by these
      iron species. Catalase was very effective in inhibiting neutrophil inactivation.
      Superoxide dismutase was not as effective but the combination with catalase was
      most effective.

PMID- 8135544
TI  - Determination of superoxide and ascorbyl radicals in the circulation of animals
      under oxidative stress.
AB  - Quantitation of the superoxide radical and its related metabolites in vivo is
      practically difficult predominantly because of their short biological half-lives.
      Though oxidized cytochrome c (cyt c) has been used for determining superoxide
      radicals in vitro, it cannot be used for in vivo analysis because of its low
      specificity as an electron acceptor and rapid disappearance from the circulation.
      To measure superoxide radicals and related metabolites in normal and pathologic
      subjects, we have synthesized a cyt c derivative (SMAC) with prolonged half-life
      in the circulation (T1/2 = 130 min) by conjugating acetylated cyt c with
      poly(styreneco-maleic acid) butyl ester (SM). An SM-conjugated superoxide
      dismutase (SM-SOD) with prolonged in vivo half-life was also synthesized. When
      injected intravenously to the rat, SMAC was rapidly reduced in the circulation of
      normal rats. The rate of SMAC reduction was markedly increased by intravenous
      administration of menadione, a compound capable of redox cycling and generating
      superoxide. The rate of SMAC reduction was not inhibited by a large dose of SM
      SOD (27,000 unit/kg) in both normal and menadione-treated animals. The rate of
      SMAC reduction also increased in animals which were administered alloxan, a
      diabetogenic agents. In contrast to the experiments with menadione, the alloxan
      enhanced reduction of SMAC was significantly inhibited by SM-SOD. Kinetic
      analysis using ascorbate oxidase suggested that ascorbyl radical was principally
      responsible for the SM-SOD-insensitive reduction of SMAC. Streptozotocin, another
      diabetogenic agent, failed to increase the rate of SMAC reduction. Thus, the
      effect of streptozotocin on the redox state of animals and the mechanism of its
      diabetogenic action might differ from those of alloxan. Combined use of SMAC and
      SM-SOD might permit quantitative studies on the occurrence of ascorbyl and
      superoxide radicals in the circulation of animals challenged with oxidative
      stress.

PMID- 8135545
TI  - 4'-Amino-benzamido-taurocholic acid selectively solubilizes glycosyl
      phosphatidylinositol-anchored membrane proteins and improves lipolytic cleavage
      of their membrane anchors by specific phospholipases.
AB  - Glycosyl-phosphatidylinositol-anchored membrane proteins (GPI-proteins) are
      normally identified either by cleavage of the lipid anchor using
      (glycosyl)phosphatidylinositol-specific phospholipases C or D (GPI-PLs) or by
      metabolic labeling of the lipid moiety with specific building blocks. Therefore,
      methods for discrimination between transmembrane proteins and GPI-proteins on the
      basis of their physicochemical properties are desirable. Here we are presenting a
      selective extraction method for typical well-characterized mammalian GPI
      proteins, e.g., acetylcholine esterase, alkaline phosphatase, 5'-nucleotidase,
      and lipoprotein lipase, using a derivative of taurocholate. The results were
      compared to those obtained with well-characterized transmembrane proteins, e.g.,
      insulin receptor and hydroxymethyl glutaryl coenzyme A-reductase, glucose
      transporters, or aminopeptidase M and several commercially available detergents.
      With regard to total membrane proteins, it was possible to selectively enrich GPI
      proteins up to 8- to 14-fold by using concentrations between 0.1 and 0.3% of 4'
      NH2-amino-7 beta-benzamido-taurocholic acid (BATC). In addition, the cleavage
      specificity and efficiency of (G)PI-PLs were increased in the presence of
      identical concentrations of BATC compared to commonly used detergents, e.g.,
      Nonidet P-40. Therefore, the present study shows that the use of BATC facilitates
      the identification of glycosyl-phosphatidylinositol-anchored membrane proteins.

PMID- 8135546
TI  - Excess membrane cholesterol is not responsible for metabolic and bioenergetic
      changes in AS-30D hepatoma mitochondria.
AB  - Using mitochondria isolated from normal rat liver and AS-30D hepatoma in addition
      to cholesterol-enriched mitochondria, we have evaluated the ability of membrane
      cholesterol to induce changes in mitochondrial function, specifically, the
      preferential export of citrate (i.e., truncation of the Krebs cycle). Two in
      vitro cholesterol-enrichment procedures failed to produce mitochondria with any
      physiologically significant increases in free membrane cholesterol.
      Alternatively, male Wistar rats were maintained on a 2% cholesterol diet to
      elevate mitochondrial cholesterol. This treatment resulted in liver mitochondria
      which contained 70% of the cholesterol levels found in AS-30D hepatoma
      mitochondria, yet only minor metabolic and bioenergetic alterations.
      Subfractionation of the various mitochondrial preparations revealed that
      cholesterol was located primarily in outer membranes of both the cholesterol
      enriched and AS-30D preparations. We therefore conclude that an increase in
      membrane cholesterol is not sufficient to induce "truncation" of the citric acid
      cycle or any other mitochondrial abnormality in tumor cells.

PMID- 8135547
TI  - Casein kinase II of Saccharomyces cerevisiae contains two distinct regulatory
      subunits, beta and beta'.
AB  - The subunit composition of casein kinase II (CKII) from S. cerevisiae has been
      difficult to define, particularly with respect to the existence and number of
      regulatory (beta) subunits. A single, integral beta subunit, a loosely associated
      beta subunit, two distinct beta subunits, and a complete absence of beta subunits
      have all been proposed. Our laboratory reported yeast CKII to be composed of four
      polypeptides of 42, 41, 35, and 32 kDa (R. Padmanabha and C. V. C. Glover, 1987,
      J. Biol. Chem. 262, 1829-1835). The 42- and 35-kDa polypeptides were identified
      as distinct catalytic subunits, alpha and alpha', on the basis of N-terminal
      sequencing and subsequent molecular cloning. The 41- and 32-kDa polypeptides were
      found to undergo autophosphorylation, a characteristic of the beta subunit in
      other species, but antibodies raised against the beta subunit of Drosophila CKII
      crossreacted only with the 41-kDa polypeptide. In order to clarify the subunit
      composition of yeast CKII, particularly with regard to the 32-kDa polypeptide, we
      have purified the enzyme to homogeneity using a modified procedure. Based on the
      results of autophosphorylation studies, Western blotting, peptide mapping of the
      41- and 32-kDa peptides, and sequencing of subunit-specific peptides, we
      demonstrate that the 32-kDa polypeptide is an additional beta subunit (beta')
      distinct from the 41-kDa beta subunit. This represents the first demonstration of
      beta subunit heterogeneity in purified CKII from any species.

PMID- 8135548
TI  - Thioredoxin-linked reductive inactivation of venom neurotoxins.
AB  - Thioredoxin, a 12-kDa protein with a catalytically active disulfide group, has
      recently been found to reduce intramolecular disulfide bonds in a variety of
      proteins. We now report that thioredoxin, reduced either enzymically with NADPH
      and NADP-thioredoxin reductase or chemically with dithiothreitol or lipoic acid,
      acts as a specific reductant of purified snake venom neurotoxins, a diverse group
      of disulfide proteins. Included were Bungarus multicinctus neurotoxins that act
      presynaptically (beta-bungarotoxin) or postsynaptically (alpha-bungarotoxin) as
      well as a postsynaptic neurotoxin from Laticauda semifasciata (erabutoxin b). We
      also observed a thioredoxin-specific reduction with other disulfide proteins of
      venom from Bungarus multicinctus, scorpion (Androctonus australis), and bee (Apis
      mellifera). Other cellular sulfhydryl agents, glutathione and glutaredoxin, were
      uniformly inactive. Thioredoxins from bacterial, plant, and animal sources were
      all active in neurotoxin reduction, but differed in effectiveness. Reduction of
      the neurotoxins by thioredoxin was accompanied by an increased susceptibility to
      tryptic proteolysis and a decrease of associated toxin activity: phospholipase A2
      (beta-bungarotoxin, snake, and bee venoms) or acetylcholine receptor binding
      (alpha-bungarotoxin). These findings extend the function of thioredoxin to the
      reduction of a broad group of low-molecular-weight proteins, all containing
      intramolecular disulfide bonds. The loss of activity accompanying reduction
      raises the possibility that venoms may be detoxified by thioredoxin either as a
      defense mechanism or as a clinical antidote.

PMID- 8135549
TI  - Tryptophan-free Escherichia coli F1-ATPase.
AB  - We have engineered a mutant form of Escherichia coli F1-ATPase which is
      tryptophan-free and contains five mutations, namely delta W28L/alpha W513F/gamma
      W108Y/gamma W206Y/beta W107F. A strain carrying all five mutations grew normally
      by oxidative phosphorylation. Purified mutant F1-ATPase showed Vmax and Km both
      65% higher than wild-type, resulting in kcat/Km the same as wild-type. The pH
      dependence of ATPase activity in mutant enzyme was very similar to that in wild
      type. Catalytic-site nucleotide-binding characteristics were measured using the
      analog lin-benzo-ADP and sensitivity to inhibitors was tested using
      dicyclohexylcarbodiimide, azide and aurovertin. The mutant enzyme was very
      similar to wild-type in each of these characteristics. The fluorescence spectrum
      of mutant enzyme confirmed the absence of tryptophan. We have therefore
      established that it is possible to generate a tryptophan-free enzyme which
      retains normal catalytic function, oligomeric stability and in vivo assembly.

PMID- 8135550
TI  - Synaptic plasma membrane structure and polarity of long-sleep and short-sleep
      mice.
AB  - Membrane dielectric as a primary basis for effects of ethanol was examined in
      synaptic plasma membranes (SPM) of genetically selected ethanol-sensitive long
      sleep (LS) and ethanol-resistant short-sleep (SS) mice. Multifrequency phase and
      modulation of fluorometry of diphenylhexatriene (DPH) was used to resolve
      structural and dielectric differences in the membrane interior core. Fluorescence
      spectral peak ratios, fluorescence lifetime analysis, and initial rates of
      photoreaction of DPH in SPM provided sensitive measures of SPM interior core
      dielectric properties. The membrane microenvironment sensed by DPH was more polar
      in SPM from SS mice than in SPM from LS mice. Physiological concentrations of
      ethanol in vitro (25-75 mM) increased the SPM interior core dielectric and
      potentiated photoreaction of DPH with other membrane components of SPM from LS,
      but not SS, mice. These effects of ethanol in vitro were maximal by 75 mM ethanol
      and/or exacerbated at higher ethanol. In addition, ethanol in vitro increased the
      fraction of DPH associated with photoreaction products with lipids from SPM of
      ethanol-sensitive LS mice. The data were consistent with ethanol in vitro
      increasing the polar molecules (ethanol and/or water) of SPM from LS but not SS
      mice. It is suggested that ethanol alters the polarity and increases reactivity
      of the interior core lipid-protein interface.

PMID- 8135551
TI  - Increased production of reactive oxygen species by rat liver mitochondria after
      chronic ethanol treatment.
AB  - Rat liver microsomes and, to a lesser extent, nuclei were previously shown to
      produce reactive oxygen species at elevated rates after chronic ethanol
      treatment. The ability of intact rat liver mitochondria to interact with iron and
      either NADH or NADPH, and the effects of ethanol treatment, on production of
      reactive oxygen intermediates was determined. In the presence of ferric-ATP, NADH
      or NADPH catalyzed mitochondrial lipid peroxidation. Rates were elevated two- to
      threefold with mitochondria from ethanol-fed rats with both reductants.
      Mitochondrial lipid peroxidation was insensitive to superoxide dismutase,
      catalase, or hydroxyl radical scavengers but was sensitive to GSH and anti
      oxidants such as trolox. Mitochondrial generation of hydroxyl radical-like
      species (assayed by oxidation of chemical scavengers) was increased after chronic
      ethanol treatment, as was H2O2 production. Modifiers of mitochondrial metabolism
      such as rotenone, cyanide, or an uncoupling agent, had no effect on mitochondrial
      production of reactive oxygen intermediates. The membrane-impermeable thiol
      reagent, p-chloromercuribenzoate, was complete inhibitory with both mitochondrial
      preparations. The activity of the rotenone-insensitive NADH-cytochrome c
      reductase, an enzyme of the outer mitochondrial membrane, was increased 40 to 60%
      by the ethanol treatment. These results suggest that NADH acting via the outer
      membrane NADH reductase can catalyze an iron-dependent production of oxygen
      radicals by rat liver mitochondria. The outer mitochondrial membrane fraction,
      prepared by digitonin fractionation, displayed increased rotenone-insensitive
      NADH-cytochrome c reductase activity after ethanol treatment and was more
      reactive in catalyzing scission of pBR322 DNA from the supercoiled form to the
      open circular forms. Rates of oxygen radical production by mitochondria and the
      extent of increase produced by chronic ethanol treatment are similar to those
      previously found with microsomes when NADH is the cofactor. Oxidation of ethanol
      by alcohol dehydrogenase generates NADH, and NADH-dependent production of
      reactive oxygen species by various organelles is increased after chronic ethanol
      treatment. These acute metabolic interactions coupled to induction by chronic
      ethanol treatment may play an important role in the development of a state of
      oxidative stress in the liver by ethanol.

PMID- 8135552
TI  - Incorporation of [3H]ethanolamine into a single cytosolic protein in a cell free
      system: ethanolaminylation of EF-1 alpha in vitro.
AB  - Ethanolamine containing modifications of cytosolic proteins have only been
      described for elongation factor 1 alpha (EF-1 alpha) which contains two
      ethanolamine-phosphoglycerol moieties at Glu 301 and 374 (Whiteheart et al.
      (1989) J. Biol. Chem. 264, 14334-14341 and Dever et al. (1989) J. Biol. Chem.
      264, 20518-20525). In this report, we describe a cell-free, cytosolic extract
      which specifically incorporates [3H]ethanolamine into a single cytosolic protein
      with properties identical to EF-1 alpha. The incorporation reaction is dependent
      on time and extract and is independent of any membrane-bound components. The
      single in vitro-radiolabeled protein is modified on two sites and chromatographic
      analysis of pronase-digested peptides is consistent with the addition of an
      unmodified ethanolamine. Ethanolaminylation does not require divalent cations or
      ATP but is inhibited by N-ethylmaleimide and stimulated by reducing agents (beta
      mercaptoethanol and dithiothreitol), indicating the requirement for free
      sulfhydryls. The nucleophile, hydroxylamine, at low concentrations, greatly
      inhibits the incorporation reaction, indicating the importance of an
      electrophilic center. This cytosolic extract appears to be able to carry out only
      the initial step in the addition of the ethanolamine-phosphoglycerol moieties to
      EF-1 alpha, and subsequent addition of the phosphoglycerol moiety appears to
      require membrane components.

PMID- 8135553
TI  - Isolation of nonlabile human ceruloplasmin by chromatographic removal of a plasma
      metalloproteinase.
AB  - Ceruloplasmin (EC 1.16.3.1) is a copper-containing alpha 2-glycoprotein and a
      member of the acute phase reactant family. Fragmentation of ceruloplasmin during
      purification and storage has hampered studies of its structure, but it has been
      shown to be a 132-kDa monomer. Combining two published chromatographic steps with
      additional gel filtration and fast protein liquid chromatography (FPLC) steps, we
      now report a procedure that yields a highly purified and nonlabile protein. Human
      plasma was subjected to QAE-Sephadex A-50 chromatography, precipitated with
      ammonium sulfate, and chromatographed on a hydroxyapatite column. The resulting
      protein was > 95% pure but highly unstable as determined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis; at 37 degrees C the 132-kDa protein
      disappeared completely within 48 h. Further purification of ceruloplasmin by
      Sephadex G-50 chromatography and Mono Q FPLC yielded a protein that was
      essentially pure by multiple criteria and completely stable even after incubation
      at 37 degrees C for 4 weeks. When purified ceruloplasmin was reconstituted with
      fractions eluted from the Sephadex G-50 column, a single fraction induced
      proteolytic degradation. The degradation of ceruloplasmin by this fraction was
      inhibited by EDTA and 1,10-phenanthroline, indicating that a plasma
      metalloproteinase is responsible for degradation of ceruloplasmin.

PMID- 8135554
TI  - The permeation of pyridoxal 5'-phosphate in chicken liver peroxisomes.

PMID- 8135555
TI  - Helicobacter pylori and gastrointestinal symptoms.

PMID- 8135556
TI  - Bronchoalveolar lavage.
AB  - Bronchoalveolar lavage has a well established role in the diagnosis of pulmonary
      infections, particularly those due to opportunistic organisms in an
      immunocompromised host. Recent studies of infants and adults with inflammatory
      lung disease have helped our understanding of the mechanisms underlying these
      disorders and their responses to treatment. With increasing recognition that
      pulmonary events in utero and in early infancy are important in the pathogenesis
      of lung diseases such as asthma, studies of the lung's responses to various
      environmental insults in this population might guide us to developing effective
      preventative and therapeutic strategies. Bronchoalveolar lavage is one method for
      assessing a number of pulmonary components and may be useful in this regard,
      particularly if combined with new methods for examining inflammatory responses,
      such as those utilising the polymerase chain reaction to assess cellular
      expression for inflammatory cytokines and growth factors.

PMID- 8135557
TI  - Prednisolone and salbutamol in the hospital treatment of acute asthma.
AB  - The use of oral prednisolone (2 mg/kg) to treat children admitted to hospital
      with acute asthma was assessed in a placebo controlled study. Children were
      further randomised to receive either 0.15 mg/kg salbutamol every 30 minutes for
      the first three hours of admission, or 5 mg salbutamol every one to four hours as
      needed. Treatment was double blind and the assessor was unaware of the nebuliser
      regimen given. Children were examined before and after treatment with salbutamol
      on arrival and reassessed four hours after admission. Seventy children completed
      the study. Seventeen (46%) of 37 children receiving prednisolone and six (9%) of
      33 receiving placebo were fit for discharge after four hours of treatment. There
      was no significant difference between the two nebuliser regimens. Clinical
      parameters indicative of asthma severity were improved in all groups. Between
      group comparisons at reassessment showed higher peak flows in those receiving
      prednisolone and nebulisers every 30 minutes but differences were not significant
      for other parameters. Objective parameters indicating steroid efficacy over
      placebo were minimal. Despite this, those receiving prednisolone were more
      readily identifiable as being fit for discharge within four hours of treatment.

PMID- 8135558
TI  - A national survey of asthma prevalence, severity, and treatment in Great Britain.
AB  - Parents of 5472 children aged 5-17 years from 3209 families were interviewed in a
      nationwide household survey. In the past year, 15.0% of children had wheezed,
      2.2% had more than 12 attacks, and 2.3% had experienced a speech limiting attack.
      Altogether 4.3% were woken more than once a week by wheezing, 13.1% had doctor
      diagnosed asthma, and 13.6% had been prescribed antiasthmatic drugs in the past
      year. With increasing age, morbidity related to wheezing declined to a greater
      extent than annual period prevalence. The prevalence of wheeze varied little by
      socioeconomic group, but there were marked trends in all three indices of
      severity towards increased morbidity in poorer families. Diagnostic labelling and
      drug treatment of wheezy children did not differ substantially with socioeconomic
      status. Thus, a degree of socioeconomic equality exists in the process of medical
      care for childhood asthma in Britain. This does not appear to have resulted in
      equality of outcome.

PMID- 8135559
TI  - Age related IgG subclass concentrations in asthma.
AB  - The prevalence of IgG subclass deficiency in asthma is still controversial.
      Earlier studies often included patients receiving treatment with systemic
      steroids which can induce hypogammaglobulinaemia. Concentrations of IgG
      subclasses were studies in 200 children (aged 2-17 years) with asthma (mean
      asthma severity score (ASS) 2, range 1-4) who had not received systemic steroids
      for at least six weeks before investigation, and in 226 healthy age matched
      controls. The mean concentrations of IgG subclasses in children with asthma were
      within the 1SD range of those of the control group. In the group with asthma
      there was a trend towards higher levels of IgG1 and IgG4, whereas the number of
      children with low concentrations of IgG2 (< 2 SD of control serum samples;
      absolute concentrations 0.08-1.25 g/l) was slightly greater than in the group who
      did not have asthma (4.5 v 2.2%). Patients with subnormal concentrations of IgG2
      could not be distinguished clinically or on the basis of case history and
      additional immunological studies did not show further abnormalities. Patients
      with severe asthma (ASS 3-4) had significantly higher concentrations of IgG4
      (mean (SE) 0.53 (0.09) v 0.26 (0.04) g/l) than patients with mild asthma (ASS 1).
      No significant difference in subclass concentration was found between patients
      with atopic and those with non-atopic asthma. It is concluded that in an
      unselected group of children with asthma the mean IgG subclass concentrations do
      not differ significantly from a group of healthy age matched controls.

PMID- 8135560
TI  - Features of transient hypogammaglobulinaemia in infants screened for
      immunological abnormalities.
AB  - The incidence of transient hypogammaglobulinaemia of infancy (THI) detected in a
      major paediatric centre over a 10 year period was examined. A total of 2468
      subjects less than 2 years of age had an IgG measurement taken between July 1979
      and March 1990. Subjects with known immunodeficiencies were excluded. Fifteen
      patients were classified as having THI with an initial IgG level less than the
      fifth centile followed by a second measurement within the normal range. A further
      24 patients were identified as having possible THI with a single low IgG
      concentration. There were 60,174 live births each year in Victoria in the years
      1979-88. This gives an incidence of proved THI of 23 per 10(6) births, and
      including proved and probable THI an incidence of 61 per 10(6) live births. Of
      those patients with proved THI 12/15 had symptoms of either atopic disease or
      food allergy/intolerance and three had gastrointestinal symptoms without any
      evidence of atopic disease. At presentation 12/15 (80%) were IgA deficient and
      9/15 had IgM concentrations less than the 20th centile for age. It is suggested
      that in view of the preponderance of atopic and food intolerant patients that
      subclinical protein loss from the bowel due to allergic inflammation may be a
      contributing factor to the development of THI in some patients.

PMID- 8135561
TI  - Thermal balance and metabolic rate during upper respiratory tract infection in
      infants.
AB  - Sequential recordings were made in the first five months after birth of metabolic
      rate, environmental temperature, and body temperature during sleep at home in 17
      infants, each with an older sibling. Further recordings were made whenever an
      older sibling developed an upper respiratory tract infection (URTI), again four
      to six days later, and again two weeks later, aiming to achieve recordings
      before, during, and after an URTI in the infant. The temperature of the room and
      wrapping of the infant were determined according to their usual practice by the
      parents. Parents added appropriate wrapping to achieve thermal neutrality based
      on our calculated values and the measured oxygen consumption. In five of the six
      infants who developed an URTI in the first three months after birth there was no
      change or a decrease in metabolic rate at the time of the infection; for infants
      older than 3 months the metabolic rate increased in three of the five episodes
      recorded. Peripheral skin temperature decreased at the time of URTI at all ages,
      though in the older infants it usually increased in parallel with rectal
      temperature during the latter part of the night, when pyrexia was most common.
      Infants thus respond to URTI by heat conservation. In the younger infants the
      lower metabolic rate and the further decrease in this rate with URTI means that
      fever is rare, and their temperature may decrease on infection. In the older
      infants the increase in metabolic rate (from an already higher baseline) may
      result in fever. These differences may contribute to the increased vulnerability
      of the older infants to heat stress, particularly at the time of acute viral
      infections.

PMID- 8135562
TI  - Genital examination under ketamine sedation in cases of suspected sexual abuse.
AB  - Sedation for genital examination in suspected sexual abuse is seldom discussed.
      The cases are presented of three children in whom genital examination was
      facilitated by ketamine sedation; these children could not be examined under any
      other circumstances. Ketamine provides safe, effective sedation, analgesia, and
      amnesia in an ambulatory setting. Its use should be considered in selected
      patients.

PMID- 8135563
TI  - Assessment of health status in survivors of cancer.
AB  - The health status of 48 survivors of cancer was assessed using a rating system
      for six attributes: senses, mobility, emotion, cognition, self care, and pain.
      Paired assessments were made by doctors and patients (or their parents, or both)
      at routine clinic attendances. Sixteen (33%) assessments by the patient/parent
      and 19 (40%) assessments by the doctor identified no deficits in health status.
      The doctors identified fewer deficits in all attributes than the
      patients/parents, the differences being most marked for subjective attributes.
      Health status index scores on a scale of 0 (worst health state) to 1 (perfect
      health) were derived from the rating system and showed good overall agreement
      between the doctors and the patients/parents. Survivors of neuroaxial tumours
      tended to have lower scores than other diagnostic groups. This simple, compact
      system could be used in clinical trials to compare treatment strategies in terms
      of the health status of survivors. It could also be a valuable tool in the
      assessment of health status in other areas of paediatrics.

PMID- 8135564
TI  - Hospital admissions before the age of 2 years in Western Australia.
AB  - A linked data file of birth records and hospital admissions was used to
      investigate inpatient hospital morbidity before 2 years of age for all non
      Aboriginal and Aboriginal children born in Western Australia in 1986. Of the non
      Aboriginal children, 31.8% were admitted to hospital at least once before the age
      of 2 years, with an overall admission rate of 526/1000 live births; the
      corresponding figures for Aboriginal children were 68.7% and 2797. The mean
      number of days in hospital for each non-Aboriginal child admitted was 7.4, and
      26.5 for Aboriginal children. Of the total cohort, 21% of non-Aboriginal and 20%
      of Aboriginal children were admitted only once, and 4% of non-Aboriginal and 36%
      of Aboriginal children were admitted at least three times; 23% of non-Aboriginal
      and 24% of Aboriginal children were admitted for only one major disease category,
      and 1% of non-Aboriginal and 16% of Aboriginal children were in at least four
      categories. The highest admission rates and highest percentages of the cohort
      admitted were for gastrointestinal and respiratory diseases and social
      admissions. These results illustrate the importance for both descriptive and
      analytical research of relating admissions to hospital for the total population
      to the individual child, and of using clinically relevant disease
      classifications.

PMID- 8135565
TI  - Need for follow up in coeliac disease.
AB  - The use of follow up studies was evaluated in 128 patients with coeliac disease
      during their first visit to a department for adults. The original diagnosis had
      been made in childhood in all patients. Fifty eight (45%) of the subjects were
      following a gluten free diet, 23 (18%) were following a gluten free diet but with
      occasional gluten consumption, and 47 (37%) had adopted an unrestricted, gluten
      containing diet for a mean of 11.2 years. There was no correlation in individual
      subjects between the presence of symptoms, biochemical and immunological
      abnormalities, severity of histological findings, and the amount of dietary
      gluten, despite the greater frequency of symptoms in the group following an
      unrestricted diet than in the other two groups. Short stature and epilepsy with
      cerebral calcifications only occurred in patients following an unrestricted diet.
      As only diagnosis based on two or three biopsy samples and regular follow up
      correlated positively with dietary compliance, it is suggested that a
      histologically confirmed diagnosis of coeliac disease and regular lifelong follow
      up are essential in the management of these patients.

PMID- 8135566
TI  - Presentation, acute illness, and learning difficulties in salt wasting 21
      hydroxylase deficiency.
AB  - The presentation, pattern of acute illness, and incidence of learning
      difficulties are described in 63 (33 boys, 30 girls) children with salt wasting
      21-hydroxylase deficiency, drawn from a cohort study of congenital adrenal
      hyperplasia in the South West Region of England between 1968 and 1988. Thirty
      boys presented with a salt losing crisis from birth whereas the other three boys
      presented between 2 and 14 months of age with failure to thrive and
      hyponatraemia. Diagnostic uncertainty led to 13 (43%) of 30 girls developing a
      salt losing crisis. Five girls were misassigned as boys at birth. There were four
      deaths in the group, two due to salt losing crisis, one to complications of
      prematurity possibly compounded by 21-hydroxylase deficiency, and one from heart
      failure probably related to an excess of steroids. Acute admissions were common,
      especially during the first year of life, with convulsions in 7% of admissions.
      The 9% incidence of hypoglycaemia was considered to be an underestimate as blood
      glucose was measured in only 56 (22%) of 254 admissions. No convulsions occurred
      in the 38 (15%) admissions where the parents had given intramuscular
      hydrocortisone before bringing the child to hospital. A high incidence of
      learning difficulties was found among the 59 surviving children (9/30 (30%) boys
      and 6/29 (21%) girls), and in only two children could any factor other than 21
      hydroxylase deficiency be invoked. Analysis of the subgroup with learning
      difficulties indicated that they were more ill at presentation with a
      significantly higher incidence of hypoglycaemia, and that growth in the first
      year was significantly worse. It is concluded that congenital adrenal hyperplasia
      remains a formidable disorder with an appreciable mortality and morbidity. The
      high incidence of learning difficulties seen in salt wasting 21-hydroxylase
      deficiency needs further attention. A prospective study is indicated to examine
      the effect of neonatal screening on morbidity from congenital adrenal
      hyperplasia, particularly the intellectual impairment seen in this study.

PMID- 8135567
TI  - Survival from acute non-lymphocytic leukaemia, 1971-88: a population based study.
AB  - Survival rates were studied among 1258 children with acute non-lymphocytic
      leukaemia diagnosed in 1971-88 and included in the population based National
      Registry of Childhood Tumours. Of the total, 147 (12%) died without receiving
      treatment. Among the remaining treated children, actuarial five year survival
      rates were 6% in 1971-4, 15% in 1975-9, 23% in 1980-3, and 40% in 1984-8. Infants
      aged less than 1 year had a significantly worse prognosis and there was a
      significant trend towards lower survival rates with increasing white cell count.
      No independent significant effects on survival were found with sex, French
      American-British (FAB) subtype, or the presence or absence of Down's syndrome.
      Children entered in national trials had a higher survival rate than those who
      were not entered, and children treated at teaching hospitals had a higher
      survival rate than those who were treated elsewhere. Among the 535 (43%) children
      who survived at least one year from diagnosis no factor studied had a significant
      effect on survival, emphasising the importance of achieving first remission as a
      determinant of long term survival.

PMID- 8135568
TI  - Review of child development teams.
AB  - Since the Court report was published in 1976 there has been a consensus that the
      needs of children with disabilities are best met by child development teams. This
      study explored the structure, facilities, and organisational elements of child
      development teams operating in the South East Thames region by means of a
      structured interview with senior professionals involved with organising services
      for children with disabilities in 14 of 15 health districts in the region.
      Although all districts had a designated child development team, not all core
      professionals were adequately represented and four of 14 districts had no child
      development centre. The quality of buildings and facilities was variable. Teams
      that did not have a physical base in the form of a centre had fewer staff in the
      service and poorer facilities. There is a need for further consensus work about
      broad guidelines on the requirements of child development teams. These will help
      to inform purchasing authorities about the needs of children with disabilities
      living in their districts.

PMID- 8135569
TI  - Postnatal somatic and mental development after periconceptional multivitamin
      supplementation.
AB  - The effect of periconceptional multivitamin supplementation on postnatal
      development was studied in a randomised controlled trial comparing the use of a
      multivitamin tablet (Elevit Pronatal) with a tablet containing trace elements as
      part of the Hungarian Optimal Family Planning Programme. Of 4122 liveborn
      infants, 3356 were examined after the eighth month of life and medical records
      were obtained for a further 357; thus the total number of infants evaluated was
      3713 (90.1%). The mortality was not significantly different between the groups
      receiving the multivitamins (9.6/1000) and trace elements (7.1/1000). There was
      no significant difference in the rates of serious or chronic disorders between
      the study groups except for atopic dermatitis, which was reported more often in
      the group receiving multivitamins (15 v four cases). Somatic development (body
      weight, body length, and head circumference) did not show a significant
      difference between the two groups. Mental and behavioural development was also
      similar in the two groups.

PMID- 8135570
TI  - Eating habits and attitudes of mothers of children with non-organic failure to
      thrive.
AB  - The eating habits and attitudes concerning body shape and weight among 26 mothers
      of children with non-organic failure to thrive (the index group) were studied
      using the eating disorder examination. They were compared with equivalent data on
      26 individually matched women who participated in a large community survey. The
      index mothers' views of their child's weight and shape were also studied. The
      principal findings were, firstly, that when compared with the comparison group,
      mothers of children with non-organic failure to thrive had higher levels of
      dietary restraint. Secondly, despite their child's low weight, 50% of the index
      mothers were restricting their child's intake of 'sweet' foods, and a further 30%
      were restricting foods they considered 'fattening' or 'unhealthy'. These results
      raise the question of whether maternal eating habits and attitudes have a causal
      role in the genesis of non-organic failure to thrive. They suggest that careful
      inquiry about the mothers' eating habits and attitudes is needed when assessing
      children with non-organic failure to thrive.

PMID- 8135571
TI  - Pneumocystis carinii pneumonia in vertically acquired HIV infection in the
      British Isles.
AB  - In order to review the clinical course, laboratory findings, and outcome of
      children with vertically acquired HIV infection and Pneumocystis carinii
      pneumonia, questionnaires were sent to paediatricians in the British Isles who
      had reported P carinii pneumonia and HIV infection through the British Paediatric
      Surveillance Unit (BPSU). Paediatric reports from the BPSU are linked to reports
      of pregnancies in HIV positive women and laboratory reports. P carinii pneumonia
      was the most frequently reported AIDS indicator disease at AIDS diagnosis,
      occurring in 22/56 (40%) children born in the British Isles; in a further two
      children P carinii pneumonia occurred after another AIDS indicator disease. The
      median age at P carinii pneumonia diagnosis was 4.1 (1.4-27.3) months and in 48%
      it occurred with other AIDS indicator diseases. Despite intensive treatment the
      three month survival was only 38%. The nine children surviving P carinii
      pneumonia subsequently developed further AIDS indicator diseases, in particular
      HIV encephalopathy and four have since died. P carinii pneumonia was present at
      AIDS diagnosis in 65% of children developing AIDS in the first year of life and
      caused 82% of infant deaths. Most children were not known to be at risk of HIV
      until they presented with P carinii pneumonia. Children with HIV infection
      develop P carinii pneumonia at an early age and have a poor outcome. Increased
      awareness of the condition is required to initiate early treatment. Prevention
      may be a compelling incentive for screening in pregnancy, but further study is
      required to quantify the risks and benefits of initiating early P carinii
      pneumonia prophylaxis as well as the impact this might have on life expectancy.

PMID- 8135572
TI  - Out of hospital needlestick injuries.
AB  - Retrospective analysis showed that 67 children had presented in Edinburgh with
      needlestick injuries on 70 occasions over five years. Worryingly, 10 children
      sustained injuries pretending to be intravenous drug abusers. Despite risks of
      hepatitis B and HIV infection, protection and follow up were inadequate.
      Publicity about discarded needles and a treatment plan for use in accident and
      emergency departments are recommended.

PMID- 8135573
TI  - Surface area estimation: pocket calculator v nomogram.
AB  - Three sheets of 10 surface area determinations were completed by 10 subjects
      using a nomogram and a formula. The formula was faster to calculate, 4.27 v 7.6
      minutes for each sheet, and resulted in fewer serious errors (three v 30 errors).

PMID- 8135575
TI  - Cystic fibrosis identified by neonatal screening: incidence, genotype, and early
      natural history.

PMID- 8135574
TI  - Vitamin K prophylaxis in the newborn--again.

PMID- 8135576
TI  - Parental participation in case conferences.

PMID- 8135577
TI  - Parental participation in case conferences.

PMID- 8135578
TI  - Sudden infant death syndrome.

PMID- 8135579
TI  - The physician's hands and early detection of neuroblastoma.

PMID- 8135580
TI  - [Histological aspects of mycotic infections in acquired immunodeficiency syndrome
      (AIDS)].
AB  - After some general epidemiological data concerning mycoses occurring during the
      acquired immunodeficiency syndrome (AIDS), the role of the pathologist in the
      diagnosis of mycotic diseases is reviewed. Histological methods and criteria
      allowing fungal identification in tissues are described. Changes in the
      inflammatory reaction in contact with mycoses arising in these immunodeficient
      hosts are reported. The various mycoses observed in HIV positive patients are
      then reviewed as well as their morphological features and their various sites.

PMID- 8135581
TI  - [Malignant mesothelioma: study of prognostic factors in a series of 188 cases].
AB  - From 1973 to 1990, 188 patients with pleural malignant mesothelioma entered a
      prospective study of this disease to assess the main prognostic factors. All had
      undergone thoracoscopy with endoscopic description of lesions, and multiple
      biopsies. The diagnostic yield of thoracoscopy was 98.4%. Multivariate analysis
      of main clinical, histopathological, endoscopic and radiological (including CT
      scan) parameters was performed according to Cox's model. The most favorable
      factors were: absence of weight loss at the time of diagnosis, absence of
      involvement of the visceral pleural, Butchart stage I and epithelial
      histopathological type. Thoracoscopy allowed early diagnosis of the disease and a
      subdivision of Butchart stage I into stage IA (with normal visceral pleura) and
      stage IB (with invaded visceral pleural): median survivals are 32.7 and 7 months
      respectively. Like CT scan, thoracoscopy is therefore necessary in the staging of
      malignant mesothelioma.

PMID- 8135582
TI  - [Immunohistochemistry of mesotheliomas. Technique and current diagnostic
      contribution of immunohistochemical markers. General review].
AB  - Diagnosis of mesothelioma is a difficult clinical and pathological task. The
      morphology of the neoplasm is extremely variable and is the major cause of the
      diagnostic dilemma. Malignant mesotheliomas are difficult to distinguish from
      benign reactive lesions of the pleura and from metastatic neoplasms, particularly
      adenocarcinomas and IVBAT (intravascular bronchioloalveolar tumor better referred
      to as sclerosing angiosarcoma or epithelioid hemangioendothelioma).
      Immunohistochemical studies represent a crucial diagnosis aid. A practical
      approach in different morphological situations is described and a routine
      antibody panel is proposed: the dual negativity of CEA and Leu M1 associated with
      thick "hairy" brush borders with EMA staining suggest malignant epithelial
      mesothelioma. The dual positivity of CEA and Leu M1 and the presence of thin
      smooth borders staining with EMA suggest adenocarcinomas. Behind a spindle-cell
      neoplasm the coexpression of keratin, vimentin and the presence of keratin
      positive cells infiltrating underlying tissue suggest malignant desmoplastic
      mesothelioma.

PMID- 8135583
TI  - [Mesothelial cell. Cytology. Cytochemistry. Immunocytochemistry. Contribution of
      immunolabelling to the cytodiagnosis of serous effusions with cells of
      mesothelial aspect].
AB  - This paper reviews the contribution of cytochemical and immunocytochemical
      methods to the cytodiagnosis of serous fluids. For this purpose, 1000 fluids were
      reviewed (500 pleural and 500 peritoneal samples). The most reliable
      histochemical technique is the iron stain which labels macrophages. A minimum
      immunolabelling panel (including one or two epithelial markers and vimentin),
      applied to the identification of the usual phenotypes of reactive fluids with
      mesothelial cells or with macrophages, to adenocarcinomatous fluids and to
      malignant mesothelioma fluids, is proposed. The sensitivity and specificity of
      the reaction is discussed but, altogether the value of the method appeared rather
      limited as a correct diagnosis was obtained in 95% of cases by a careful
      morphological study.

PMID- 8135584
TI  - [Flow cytometry and malignant pleural mesotheliomas. Value in the histologic and
      cytologic diagnosis].
AB  - To contribution the help of flow cytometry in the diagnosis of mesothelioma in
      pleural effusions, we studied the aneuploid frequency in paraffin-embedded
      pleural mesotheliomas. The low aneuploidy rate (31%) explains the moderate yield
      of mesothelioma diagnosis in pleural effusions. Because of the possibility of
      false aneuploidies, flow cytometry cannot replace of a cytologic or
      histopathologic evidence.

PMID- 8135585
TI  - [Anatomoclinical diversity of bronchiolitis obliterans after lung
      transplantation. Anatomical study of 16 cases among 64 transplantations].
AB  - The aim of this study was to define the presence, histological types and extent
      of bronchiolitis obliterans (BO) after lung transplantation and to discuss the
      place of bronchiolitis obliterans in the progressive obstructive ventilatory
      disorder observed in some patients and considered to correspond to "chronic lung
      rejection". The histological lesions were studied in 16 subjects surviving for
      more than one month after lung transplantation or heart-lung transplantation: 12
      autopsies, 3 surgical biopsies and one lung explanted for retransplantation.
      Thirteen subjects presented lesions of bronchiolitis obliterans: 5 cases of
      granulomatous BO, 6 cases of proliferative BO, one acute necrotising BO and one
      tuberculous granulomatous BO. Three of these patients presented an obstructive
      ventilatory disorder: one death on the 213rd day (acute necrotising BO), one
      retransplantation on the 672nd day (granulomatous BO), one death 53 days after
      surgical biopsy on the 247th day (proliferative BO). Two patients undergoing
      surgical biopsies with lesions of proliferative BO are still alive (cases 15 and
      16) and do not present any signs of obstructive ventilatory disorder. This study
      suggests the existence of various histological types of BO in transplanted lungs,
      which is not exclusively of immunopathological origin, that infections and
      various inhalations also play a role and that alterations of pulmonary structures
      other than bronchioles are also involved in the pathogenesis of the obstructive
      ventilatory disorder (functional destruction of the transplant), corresponding to
      "chronic lung rejection".

PMID- 8135586
TI  - Localized fibrous tumor of the pleura. Report of two cases with
      immunohistochemical study.
AB  - The light microscopy and immunohistochemical findings of two new cases of
      localized fibrous tumor of the pleura are reported. Both cases remained
      asymptomatic. One of them was incidentally found in a 69 year-old male during a
      thoracotomy for adenocarcinoma of the lung. The other was discovered in a 51 year
      old woman in the course of a routine chest X-ray. Bundles of tightly packed
      benign fibroblasts within a collagen-rich stroma were the histologic hallmark.
      Bizarre cells and prominent sclerosis were extensive features in the first case.
      Only vimentin showed diffuse positive immunostaining in proliferating cells. Our
      results support the fibroblastic origin proposed for this lesion.

PMID- 8135587
TI  - [Pancreatic insulinoma, adenomatosis of the Wirsung's duct and chronic
      pancreatitis. Apropos of a case].
AB  - The clinical investigations carried out in a 58 years woman complaining of
      malaise led to the discovery of an hypoglycaemia resulting from a secreting
      pancreatic insulinoma. In addition, a chronic pancreatitis, an endocrine
      hyperplasia (possible nesidioblastosis) and a villous adenomatosis of the
      pancreatic duct were diagnosed on two biopsies. The immunohistological tests
      performed on the insulinoma showed insulin, calcitonin and gastrin labelled
      cells. Electron microscopy displayed numerous neurosecretory granules. The
      peritumoral endocrine hyperplasia contained intermingled B, A and D cells
      respectively labelled by insulin, glucagon and somatostatin. Following the
      operation, the patient recovered without recurrence of the hypoglycaemia (three
      year follow-up). Factors which may explain such a rare pathological association
      are discussed.

PMID- 8135588
TI  - [The current general view of cardiac rehabilitation].

PMID- 8135589
TI  - [Calcified aortic stenosis due to healed experimental bacterial endocarditis].
AB  - We studied the role of bacterial endocarditis in the development of aortic valve
      stenosis. A femoral arterio venous shunt was performed in nine dogs with the
      method previously proposed by Lillehei. We induced bacteremic infection with the
      administration of streptococcus mitis (1 x 10(10)) 10 ml once a day for 15 days
      these bacterium were sensible to penicillin. All dogs were treated with 1,000,000
      U of benzatinic penicillin and sacrificed between 28-102 days after the bacterial
      inoculation ended. In one dog we observed bacterial endocarditis in the mitral
      and aortic valves and in other three dogs there was an aortic valve stenosis with
      calcium deposits in the body and in the free edges of the aortic valve with
      evident irregular stenosis as seen in man.

PMID- 8135590
TI  - [The transcatheter closure of patent ductus arteriosus. The initial experience].
AB  - Percutaneous closure of the patent ductus arteriosus (PDA) has been recently
      reported to be an effective alternative in the treatment of patients with ductal
      shunting. We report the initial experience and results during follow-up of
      percutaneous ductal occlusion with the Rashkind occluder (USCI) in six patients
      with isolated PDA. Ages ranged from 3 to 23 years. Diagnosis was corroborated
      with two dimensional and Doppler echocardiography in all patients. During cardiac
      catheterization systolic pulmonary artery pressure oscillated between 22 and 64
      mmHg and Qp/Qs ratio between 1.3 and 4.1. In two patients prosthesis of 12 mm
      were used and in the remaining prosthesis of 17 mm. Only one patient demonstrated
      total occlusion during immediate control aortography, the other patients
      presented central residual shunting over the occluder. In the three patients
      occlusion with balloon-catheter was added to the procedure, resulting in total
      occlusion in two and significant reduction of the shunt magnitude in one. Two
      technical problems were resolved satisfactorily. None of the cases presented
      device embolization. Mean follow-up was 23.8 months with control echocardiograms
      at 24 hours, 1, 4, 12 and 24 months. In all patients immediate reduction of the
      left atrial dimension was demonstrated. Three patients presented residual shunts
      in the first 24 hours. In two of them total occlusion had occurred after one
      month and the other patient persisted with a small residual shunt until one year
      after the procedure. In conclusion, in this small study group good results were
      obtained with percutaneous ductal closure.

PMID- 8135591
TI  - [The implant of a pacemaker cardioverter-defibrillator with a system of
      endocardial electrodes without thoracotomy].
AB  - This article describes the first case in Mexico of an implantable pacer
      cardioverter-defibrillator in a 44-year-old man with coronary artery disease and
      recurrent ventricular tachycardia without the need for a thoracotomy and
      epicardial electrodes. The patient underwent electrophysiological evaluation that
      revealed drug-refractory ventricular tachycardia. Endocardial catheter ablation
      with radiofrequency was considered and rejected due to an unstable hemodynamic
      state during the tachycardia. A triple electrode system using two transvenous
      catheter electrodes and a subcutaneous chest patch were employed. Two monophasic
      unsynchronized shocks were delivered with a 18 J sequential pulse technique over
      two distinct current pathways. The automatic pacer-cardioverter-defibrillator was
      implanted in the abdominal wall and demonstrated reproducible termination of
      ventricular fibrillation.

PMID- 8135592
TI  - [The use of the right gastroepiploic artery for posterior myocardial
      revascularization].
AB  - From August 1992 to June 1993, eight patients underwent myocardial
      revascularization in whom the right gastroepiploic artery was used in order to
      reach the posterior myocardium. All patients were men. Ages ranged from 32 to 65
      years, with a mean of 51 years. The left internal mammary artery was used in all
      patients. The right internal mammary artery was used in three patients and the
      right inferior epigastric artery was used as a free graft in one patient. There
      was three bypass grafts per patient with a total of 20 arterial grafts in which
      19 were pediculated and one as a free graft. The aortic clamping time ranged from
      52 to 80 minutes with a mean of 72 minutes. All patients received combined
      antegrade/retrograde cardioplegia delivery through the aortic root and the
      coronary sinus respectively for myocardial protection. There was no need to use
      inotropic support for ventricular assistance. The right gastroepiploic artery was
      used in order to reach the posterior myocardium and it was passed through the
      antero-hepatic trans-diaphragmatic route. There was no complications with the use
      of the right gastroepiploic artery in the early and late postoperative period.
      The course was excellent in all patients and they remain asymptomatic. We
      conclude that the use of the right gastroepiploic artery for coronary bypass
      grafting in order to revascularize the posterior myocardium is an excellent
      choice. There were no technical difficulties nor gastric complications and we are
      increasing our experience in order to establish its routine use.

PMID- 8135593
TI  - [Pulmonary valve autograft for aortic valvulopathy].
AB  - Twelve patients were operated on between February 1992 and June 1993 because
      aortic valve disease with pulmonary autograft replacement of the aortic valve and
      reconstruction of the right ventricular outflow tract with a valved tube of
      autogenous pericardium and bovine prosthetic pericardium valve made at the
      Instituto Nacional de Cardiologia Ignacio Chavez. Aortic and pulmonary annular
      diameters were taken preoperative in all patients by transthoracic
      echocardiography. During the surgical procedure, transthoracic echocardiography
      was done in order to assess valvular function of the pulmonary autograft. There
      was no peri-operative morbi-mortality and no anticoagulation was required. Post
      operative evolution was satisfactory in all patients and were discharged after
      transthoracic echocardiography evaluation. Annular diameters correlated with the
      trans-surgical annular measurements. We conclude that the use of the pulmonary
      autograft in selected cases can be done, in order to relieve aortic valve
      disease, without significant morbi-mortality as compared with single aortic valve
      replacement.

PMID- 8135594
TI  - [Percutaneous transluminal coronary angioplasty. The experience of the Hospital
      de Especialidades of the La Raza Medical Center, IMSS].
AB  - We analyzed the initial results of the PTCA program at the Hospital de
      Especialidades CMR, IMSS. During the last year we studied 33 patients in whom we
      performed 35 PTCA procedures with total of 45 lesions. The age of the patients
      varied from 27 to 75 years of age (average 57 year +/- 10.9). Among them, 84.8%
      were males and 15.2% females. In 54.5% of the patients, stable angina was
      present, whereas in 45.5% unstable angina was observed. Multivessel disease was
      detected in 39.4% of the cases. In 17.8% the coronary lesions were type "A", in
      77.8% type "B" and in 4.4% type C. The most frequent lesions were present at the
      left anterior descending artery in 46.6%, right coronary artery in 40% and
      circumflex in 13.4%. The global procedural success was 88.5% (32/35 procedure)
      whereas the procedural success by isolated lesion was 88.8% (40/45 lesions). The
      average artery stenosis was decreased from 85 +/- 10.4% to 23 +/- 16%. A
      procedural failure occurred in 4 instances (11.4%), among them, 2 (5.71%) without
      complications and 2 more, associated to acute myocardial infarction. In the
      present study there were no emergency operation neither deaths. CONCLUSIONS:
      Although the number of PTCA performed in our hospital is limited, we consider
      that the initial results are good, with a success rate of 88.5% with a minimal
      complications.

PMID- 8135595
TI  - [Acute myocardial infarct in young adults. A report of 142 cases].
AB  - We present 142 cases of myocardial infarction in the young (MIY) which correspond
      to 5.6% of a total of 2525 patients with MI hospitalized in the past 5 years at
      the Hospital de Especialidades del Centro Medico La Raza, IMSS. Among them, 124
      (87%) were males and 18 (13%) females. The age varied from 25-40 years, average
      35 years for both sexes. Occupational labor: 56 (39.5%) were workers, 27 (19%)
      officemen, 22 (15.5%) professionals, 20 (14%) taxi drivers, 15 (10.5%) merchants
      and 2 (1.5%) students. Personal cardiac history: 42 (30%) had history of angor
      pectoris and 5 (3.5%) of MI. Coronary risk factors: 106 patients (75%) had
      emotional stress due to type "A" personality, 101 (71%) cigarette smoking, 59
      (42%) systemic arterial hypertension, 35 (25%) diabetes mellitus, 35 (25%)
      hyperlipidemias and 28 (20%) obesity. Among them, 34 (24%) had no risk factors.
      MI localization: 48 (34%) anteroseptal, 37 (26%) anterolateral, 36 (25%)
      posteroinferior and 21 (15%) inferior. Only in 83 cases coronary angiogram was
      performed, among them: 34 (41%) had disease of the left coronary artery and 18
      (22%) of the right; 33 (40%) had one vessel, 15 (18%) 2 vessel and 4 (5%) 3
      vessel disease. In 31 (37%) the coronary angiogram was normal.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8135596
TI  - [Isolated agenesis of the pulmonary valve in the adult. When is the proper time
      for surgery?].
AB  - The congenital absence of the pulmonary valves is a rare malformation that mainly
      affects children, frequently is associated with other cardiac malformations and
      very rarely is present in adults. Elective or urgent surgery is indicated in the
      symptomatic child; on the other hand, surgical treatment in the asymptomatic
      adult with this anomaly is controversial. Based on the reported experience in the
      literature, in the present article, the authors discuss the therapeutic approach
      of an asymptomatic 22-year-old male with pulmonary valvular absence with
      practically no hemodynamic repercussion. Although there had been few reported
      cases of isolated pulmonary valvular absence, the authors concluded that surgery
      is not a satisfactory solution and that it might be postponed to the time that
      patients develop congestive heart failure and or respiratory insufficiency. In
      order to detect that on time, we recommend a follow up based on periodic
      echocardiographic studies.

PMID- 8135597
TI  - [The cardiovascular effects of serotonin receptor agonists and antagonists (II)].

PMID- 8135598
TI  - [Reassessment of the noninvasive reperfusion criteria in AMI patients submitted
      to pharmacological thrombolysis (II)].

PMID- 8135600
TI  - [Hygienic aspects of aerobic fermentation of urban waste in the Tunisian
      context].
AB  - The use of the aerobic fermentation (composting) as an alternative of the
      landfilling of the municipal solid wastes was studied in a pilot plant in the
      District of Tunis. The effectiveness of the composting, by the windrow turning
      technical, in producing sanitized compost was considered. Fecal coliforms, fecal
      streptococcis and E. coli were used as an indicator organism. In addition, the
      evolution of the process was monitored using sporogenous bacteria. Under the
      experimental conditions, approximately five logarithmic unit reduction of fecal
      indicators was noted after a 60 days composting.

PMID- 8135599
TI  - [The alpha-1 adrenergic response in cardiac myocytes].

PMID- 8135601
TI  - Improvement and standardization of antivenoms sera: snake venoms preparation.

PMID- 8135602
TI  - [Rehabilitation of sexual abuse in children].

PMID- 8135603
TI  - [Prevention of allergy, a specific pediatric task?].

PMID- 8135604
TI  - [Follow-up of adolescents with Turner syndrome].
AB  - BACKGROUND: Adult women suffering from Turner's syndrome were born too early to
      have been treated with growth hormone. Most of them are not familiar with the
      results of the new methods of reproductive medicine. It is thus useful to know
      their long-term development after their adolescence. PATIENTS AND METHODS: A
      questionnaire was sent to 107 young Turner women aged 18 to 35 years. It included
      data on their level of education and qualification, their social, familial and
      professional accomplishments, their sentimental and sexual status, their housing
      and their leisure activities, their opinion of themselves and of the treatment
      they had received. RESULTS: The mean subject height was 144.5 +/- 6.9 cm (range:
      130-160 cm); 50% had received an advanced education and only 1 patient suffered
      from mental retardation. 40% had a steady employment and 34% were still at
      school. 13 of the 44 patients who responded had normal sexual lives. 92% were
      interested in reading, movies, theater or music. CONCLUSIONS: These adults have
      overcome the difficulties resulting from their handicaps and are successful in
      their adaptation to the adult society. This is due to their intelligence and
      personalities.

PMID- 8135605
TI  - [Mechanical ventilation by nasal mask in children with cystic fibrosis. Initial
      results of a non-invasive method].
AB  - BACKGROUND: Chronic respiratory failure (CRF) with hypoxia and hypercapnia is the
      last ineluctable phase in cystic fibrosis (CF). Nasal positive pressure
      ventilation (NPPV), a non-invasive method, may be given to CF children with CRF,
      especially to patients accepted for transplantation (T). This method improves
      ventilatory function by resting the chronically exhausted respiratory muscles,
      facilitates bronchial drainage by physiotherapy, prevents the exacerbations of
      the illness and prepares patients for T. METHODS AND PATIENTS: NPPV was used in 6
      CF patients (mean age 13 years 6 months). One of them was transplanted 15 days
      later, two of them were accepted for T. All had hypoxia. Five of them had
      hypercapnia. RESULTS: NPPV was given to four patients for 3 to 14 months. The
      preliminary results were positive. One patient gained weight, two had more fluid
      sputum. One patient showed an increase in functional respiratory tests (FRT:
      PaO2, vital capacity, FEV-1) while these tests were stabilized in the others.
      CONCLUSIONS: NPPV in an effective non-invasive method for use with CF children.
      It is indicated for CF patients accepted for T and also earlier, for CF patients
      with CRF in order to prevent acute exacerbations and functional respiratory
      deterioration.

PMID- 8135606
TI  - [Anti-gastric antibodies and gastritis in insulin-dependent diabetes in
      children].
AB  - BACKGROUND: Adult patients with insulin-dependent diabetes mellitus frequently
      also show gastric disturbances. Knowledge of the prevalence of such abnormalities
      in children with insulin-dependent diabetes and the predictive value of anti
      gastric parietal cell antibodies in blood may be of practical importance.
      PATIENTS AND METHODS: 68 patients (29 boys and 39 girls), aged from 5 yr 2 mo to
      19 yr 10 mo, and treated for insulin-dependent diabetes from 1 mo to 14 yr 6 mo,
      were included in the study. Fasting blood concentrations of gastrin (G),
      pepsinogen (PG1), anti-gastric parietal cell antibodies (PCA) were measured.
      Fiberoptic endoscopy and biopsy of the gastroduodenal mucosa were performed in
      PCA+ patients and biopsy samples were examined for Helicobacter pylori (HP).
      RESULTS: 12 patients were PCA+; 3 of them had blood gastrin levels above 104
      pg/ml and 4 had blood pepsinogen levels 24 ng/ml. Histologically, 3 patients had
      chronic diffuse gastritis (2 were HP+); 2 had chronic gastritis restricted to the
      antro-pyloric area (both were HP+); 3 had follicular lymphoid hyperplasia
      (without HP) and 4 had normal mucosa (without HP). CONCLUSION: The presence of
      PCA can predict the risk of chronic gastritis, possibly auto-immune in origin, in
      children with insulin-dependent diabetes.

PMID- 8135607
TI  - [A controlled study of food behavior and emotional manifestation in a population
      of obese female adolescents].
AB  - BACKGROUND: Obesity is a major Public Health problem in developed countries. It
      is frequently associated with psychological difficulties that may interfere with
      treatment. PATIENTS AND METHODS: 22 obese female adolescents, aged 13 to 19
      years, and 24 age-matched female controls, were compared with regard to emotional
      pathology (anxiety, depression), eating behaviors, self-esteem, body image and
      parental history of depression. The evaluation was both categorical (DSM III-R
      criteria) and dimensional for depression and anxiety. It also included a self
      esteem scale and questionnaires. RESULTS: The obese adolescents had more
      depressive symptoms, more prevalent anxiety disorders, more frequent histories of
      parental depression, eating behaviors characterized by over-eating and/or
      restricted intake, lower self-esteem and dissatisfaction with their body image,
      leading to avoidance behaviors in some of them. CONCLUSIONS: Psychological
      manifestations, although they are still insufficiently documented, especially in
      adolescents, may aggravate obesity and interfere with treatment.

PMID- 8135608
TI  - [Acute quinine poisoning treated with high dose of diazepam].
AB  - BACKGROUND: High concentrations of quinine, the drug of choice for severe
      malaria, are toxic to the cardiovascular system, producing hypotension and
      abnormal myocardial conduction. CASE REPORT: An 8 year-old girl was admitted for
      fever, headache and arthralgias. Examination of a thick film of blood showed
      Plasmodium falciparum (parasitemia: 2%). She was given quinine intravenously.
      Ventricular tachycardia (150/min) and status epilepticus were seen 48 hours
      later, necessitating ventilatory support, plasma volume expander and IV sodium
      thiopental. On admission to an intensive care unit, the patient had hypothermia,
      was comatose (stage IV) with a reactive mydriasis and bradycardia (30/min). ECG
      confirmed bradycardia and showed a widened QRS complex. There was also a
      bilateral retinal edema. The blood level of quinine was 61 mumol/liter
      (therapeutic levels: 6-15). Retrospective inquiry revealed that the quinine
      initially administered had been incorrectly diluted. The child was treated with
      furosemide and adrenaline, followed by dobutamine and albumin infusion. She was
      then given diazepam (initial dose: 2 mg/kg then 6 mg/kg/day divided into 4 doses)
      intravenously, plus lidocaine, methylprednisolone and glycerol. The sinusal
      rhythm became normal 1 hour after the first bolus of diazepam. Consciousness
      gradually improved over the 10 days after admission while treatment was
      progressively discontinued. There were no sequelae, except for a transitory
      bilateral blindness. CONCLUSION: The cardiovascular side-effects of quinine
      poisoning can be reversed with diazepam, as has previously been reported in cases
      of chloroquine poisoning.

PMID- 8135609
TI  - [Coffin-Lowry syndrome and hyperprolinemia].
AB  - BACKGROUND: The main features of the Coffin-Lowry syndrome are mental retardation
      and features of a peculiar pugilistic nose, large ears, tapered fingers,
      drumstick terminal phalanges by X-rays and kyphoscoliosis. Inheritance is
      probably X-linked dominant. Its early diagnosis is difficult. CASE REPORT: A 31
      month-old boy was admitted for mental retardation. His weight and height were
      normal, but his facies showed telecanthus, anteverted nares and a prominent
      frontal region. His hands appeared puffy with bulbous tapering fingers. Amino
      acid chromatography showed hyperprolinemia (732 mumol/l) plus iminoglycinuria.
      His mother had a short stature, mental retardation and similar, although minor,
      manifestations of the Coffin-Lowry syndrome in her face, hands and fingers. She
      had moderate hyperprolinemia (391 mumol/l) without hyperglycinuria. The patient's
      father showed no physical abnormalities, but he also had hyperprolinemia (671
      mumol/l) and hyperglycinuria. CONCLUSION: The association of the Coffin-Lowry
      syndrome and hyperprolinemia in this family seems fortuitous.

PMID- 8135610
TI  - [Growth retardation and obstructive sleep apnea in infants].
AB  - BACKGROUND: Obstructive sleep apnea can induce growth retardation, with cardiac
      and/or neurologic manifestations. Tonsillectomy and adenoidectomy may improve
      failure to thrive. CASE REPORTS: Case n. 1: A 11 1/2-month-old boy was admitted
      because of feeding problems plus chronic nasopharyngeal secretions (eventually
      purulent) since the first months of life. He showed a low rate of weight gain
      since the age of 7 months and had been treated treated for gastroesophageal
      reflux for a few weeks. On admission, his weight was 6,220 g and his height was
      70.5 cm. The tonsils were enlarged and the uvula was long. He displayed
      tachycardia (150/min). Polygraphic recordings during sleep showed numerous
      episodes of obstructive apnea. Arterial oxygen saturation (SaO2) during the night
      was low, frequently below 80%. Tonsillectomy and adenoidectomy immediately
      improved the quality of sleep. Nocturnal SaO2 and cardiac rythm improved one week
      later; there was a catch-up weight one month after surgery. Case n. 2: A 7-month
      old boy, was admitted because chronic manifestations similar to those of case n.
      1. His weight was 5,900 g and his height was 67.5 cm. He also had enlarged
      tonsils. He suffered from episodes of snoring and obstructive sleep apnea
      followed by waking and sweating. PaO2 was 70 mmHg and PaCO2 was 48 mmHg.
      Nocturnal SaO2 was frequently below 60%. Tonsillectomy and adenoidectomy resulted
      in a net improvement in sleep and weight, despite persistent episodes of
      nocturnal hypoxemia. CONCLUSIONS: Chronic hypertrophic tonsils and adenoids can
      interfere with weight gain. Growth retardation may dramatically improve after
      surgery, even if the tonsils and adenoids do not completely obstruct the
      nasopharynx.

PMID- 8135611
TI  - [Generalized epilepsy disclosing medium-chain-acyl-CoA dehydrogenase deficiency].
AB  - BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most
      common inherited defect of fatty acid beta-oxidation. As it causes life
      threatening symptoms, it is mandatory to diagnose deficiencies of this enzyme in
      families. CASE REPORT: A boy was admitted at the age of 3 months because of a
      recent attack of generalized seizures. His parents were second cousins and one of
      his 2 sisters, 6 years old, suffered from epilepsy. At admission, the patient had
      moderate hepatomegaly; he was given clonazepam and phenytoin because of
      persistent status epilepticus. He developed a fever (temp.: 39 degrees) and a
      rash 24 hours later. A viral etiology was suggested by CSF contents of 104
      cells/mm3 and 1 g/l protein. The patient was given aciclovir. Blood glucose,
      transaminases, ammonia, lactate, pyruvate and amino acids levels were normal.
      Analysis of urine by GC-MS revealed a large lactate peak and dicarboxylic acids,
      unsaturated dicarboxylic acids, hydroxyhexanoate, 7-hydroxyoctanoate,
      hexanoylglycine and suberylglycine. This profile indicated a MCAD deficiency. The
      plasma contained partially oxidized medium-chain fatty acids, such as octanoic
      acid and especially 4-decenoic acid. the diagnosis was confirmed by a
      phenylpropionate loading test and specific enzyme assay in fibroblasts. Molecular
      studies identified a G 985 mutation in the patient and revealed that the parents
      were heterozygotes for the mutation. The condition of the patient at the age of
      18 months is excellent; he has a regular, adequate caloric intake and avoids
      fasting. He has not taken anti-epileptic drugs for the past 6 months. CONCLUSION:
      There is no typical clinical presentation of MCAD-deficiency; the most frequent
      features are vomiting and lethargy. Episodic hypoglycemia has been reported, but
      hypoglycemia was not found in our patient. Molecular studies will allow neonatal
      diagnosis of the next affected siblings.

PMID- 8135612
TI  - [Wilson disease, IgA glomerulonephritis and vascular purpura: an incidental
      association?].
AB  - BACKGROUND: IgA nephropathy may occur in adults with alcoholic cirrhosis. It has
      also been reported in children with alpha-1-antitrypsin deficiency. A case of IgA
      nephropathy associated with cirrhosis due to Wilson's disease is reported. CASE
      REPORT: A 10 year-old girl, was admitted for cirrhosis. She had suffered from
      ascitis and hematuria since the age of 6 years and vascular purpura since the age
      of 9 yr 6 mo. At admission, she had atrophic liver cirrhosis, ascitis
      splenomegaly and petechiae on her legs. There was microcytic anemia due to iron
      deficiency. The Coombs test was positive. There were hypoalbuminemia (2 g/dl) and
      polyclonal hyperglobulinemia (IgA 750 mg/dl, IgG 1670 mg/dl and IgM 250 mg/dl).
      Her serum concentrations of complement factors were normal and no immune
      complexes were detected in serum. She also showed biological changes due to
      kidney failure, hematuria and proteinuria. A liver biopsy showed micronodular
      cirrhosis with numerous plasma cells containing IgA. The search for an etiology
      showed ceruloplasmin levels of 5 mg/dl, elevated urinary copper excretion (> 150
      micrograms/day) and above normal liver copper (255 micrograms/g dry weight);
      Kayser-Fleischer ring was also seen. The renal biopsy showed
      membranoproliferative glomerulonephritis, and immunofluorescent microscopy
      revealed C3 and IgA in the mesangial and subendothelial regions. The patient was
      given spironolactone and furosemide followed by triethylenetetramine
      dihydrochloride. CONCLUSIONS: The IgA nephropathy, vascular purpura and elevated
      serum IgA levels could be due to the liver changes. If so, they should be
      improved by a liver transplant, although our patient would be a better candidate
      for combined liver and kidney transplantation.

PMID- 8135613
TI  - [Acute renal insufficiency in Kawasaki disease].
AB  - BACKGROUND: Kawasaki disease is an acute inflammatory condition characterized by
      various combinations of features but renal involvement is rare. This report is of
      a case of Kawasaki disease complicated by acute kidney failure. CASE REPORT: A 10
      year-old girl was admitted because of acute renal failure with fever. She
      developed a high fever, and her general condition was poor; she had developed a
      macular erythematous rash 10 days earlier for which she was given cefadroxil. At
      admission, she remained febrile and had strawberry tongue, pharyngitis, dry
      erythematous lips, bilateral conjunctivitis, cervical lymphadenopathy and
      desquamation of the skin on her hands. She was anemic (hemoglobin = 9.6 g%),
      leukocytotic (33,100/mm3), but with no burr, fragmented red blood cells or
      thrombocytopenia. Her plasma C-reactive protein level was 236 mg/l; her blood
      urea was 9.5 mmol/l, her creatininemia 288 mumol/l and proteinuria was 0.5 g/l
      without hematuria. Urine cultures did not grow. Her blood transaminase and
      gammaglutamyltransferase activities were elevated. Ultrasonography of kidneys and
      coronary arteries was normal. Kidney biopsy performed one day after admission
      showed no vascular or glomerular changes, but renal tubular necrosis, indicating
      urinary excretion of pigments. Tests for myoglobinemia, myoglobinuria and blood
      muscle enzyme activities were all positive. The renal failure disappeared within
      10 days but the fever and inflammatory manifestations persisted for 1 1/2-2
      months despite two treatments of intravenous gammaglobulins and continuous
      salicylate administration. The patient developed arthralgias at the end of the
      first month of disease, but recovered without renal or vascular complications.
      CONCLUSIONS: Several cases of renal involvement have been reported during the
      course of Kawasaki disease. They have been rarely documented by histological
      examination so that the vascular origin of changes has not been demonstrated.
      Myoglobinuria, as seen in muscular crush injury, and in our case possibly due to
      malignant hyperthermia, may be responsible for the transient acute renal failure.

PMID- 8135615
TI  - [Radiological case of the month: intramural hematoma of the third duodenum].

PMID- 8135614
TI  - [Neonatal shigellosis].
AB  - BACKGROUND: Neonatal shigellosis is rare and is usually encountered in unsanitary
      countries. It is occasionally responsible for manifestations of bacteremia such
      as septic shock and rash. CASE REPORT: A boy was born at 40 weeks of gestational
      age, while the end of labor was marked by temperature at 38 degrees C. His weight
      was 3,640 g and his height was 49.5 cm. The temperature of the newborn was 38
      degrees C at 1 hour of life. He had hepatomegaly and X-rays showed abdominal
      distension. Gastric aspirates taken at that time showed Gram-negative bacilli and
      Gram-positive cocci. The patient was given amoxicillin intravenously and
      netilmicin intramuscularly. The infant still had a fever at 33 hours of life and
      produced aqueous stools containing blood and mucus. At H40, he developed shock
      requiring infusion of human albumin. He was given cefotaxime and was admitted to
      the intensive care unit, where a hepatosplenomegaly was also noted. He was given
      respiratory support, albumin infusion, dobutamine and dopamine. Antibiotics
      included cefotaxime, gentamicin and metronidazole. His total white cell count was
      2,400/mm3, with 71% mature neutrophils; his platelet count was 190,000/mm3. Stool
      cultures showed the presence of Shigella flexneri, but blood cultures did not
      grow. A generalized rash was seen 4 days later; this persisted for less than 24
      hours, while the platelet count was 25,000/mm3. The patient was then given
      ceftriazone and gentamicin. His stool cultures contained Shigella flexneri on the
      4th and 9th day, but not on the 14th day. His mother had diarrhea 7 weeks before
      delivery, but stool cultures before and after delivery did not grow. CONCLUSION:
      Diagnosis of neonatal shigellosis is difficult. Cutaneous manifestations,
      possibly indicating bacteremia, have been seen in older children but never in the
      neonates.

PMID- 8135616
TI  - [Prevention of cancers in children].

PMID- 8135617
TI  - [Pediatric hematology].

PMID- 8135618
TI  - [Children's participation in biomedical research. A planned survey of 541
      parents].
AB  - BACKGROUND: We have interviewed the parents of children born at two maternity
      hospitals to evaluate the knowledge of parents concerning the French Huriet law
      and their consent to the participation of their child in a randomized therapeutic
      trial. METHODS: The inquiry was conducted between 15 February and 30 April 1991.
      Each couple of parents of whom the mother had given birth in one of the hospitals
      was sent an explanatory letter and a questionnaire on the second day after
      delivery. Parents who were unable to read adequately and those whose baby was ill
      were excluded from the study. The main questions were: age of parents, country of
      origin, education, profession, social insurance, frequency of medical consulting,
      their knowledge of the Huriet law, the source of that knowledge, their attitude
      to giving parental consent for their child to participate in a trial, the reasons
      for their consent or refusal. RESULTS: Five hundred and eighty two questionnaires
      were distributed but only 541 were used. 73% of the parents said they knew that
      drugs were tested on volunteers. 59% claimed to know of the Huriet law, through
      the media (75%), their practitionist (12%), their environment (8%). 21% of the
      parents would consent to one of their children participating in such trial; 74%
      would refuse. Both parents were in agreement in 79% of cases, 12% of them for
      consent. The main reasons for refusal were the risk for side-effects of the drug
      (75%), lack of proof for efficacy (49%), disagreement in principle (19%). The
      mothers who consented were older than those who refused. The members of the
      "consent" group were more highly educated. CONCLUSIONS: Law Huriet is still
      inadequately understood in France. Pediatricians should consider how best to
      provide parents and the media with better information before trying to obtain
      parental consent.

PMID- 8135619
TI  - [Placental Listeria infection without fetal involvement].

PMID- 8135621
TI  - [Cystic fibrosis: what is the incidence?].

PMID- 8135620
TI  - [Epidemiologic profile of celiac disease in Seine-Maritime (1972-1981)].

PMID- 8135622
TI  - [Vitamin D supplementation of dairy products in the prevention of deficiency
      induced rickets. Or: vitamin D- enriched milk for infants: new modalities of drug
      prescription for the prevention of rickets].

PMID- 8135624
TI  - The quest for preneoplastic lesions in the pancreas.

PMID- 8135623
TI  - Utility of postmortem magnetic resonance imaging in clinical neuropathology.
AB  - Over 200 brains were examined by postmortem magnetic resonance imaging to
      determine the utility of this imaging procedure as an adjunct to the standard
      postmortem examination of the brain and spinal cord. One unembalmed cadaver was
      also studied using a conventional 1.5-tesla (T) field-strength unit, and three
      formalin-fixed sections of the hippocampus were imaged using a high field
      strength (7.0-T) prototype imaging system. The postmortem magnetic resonance
      images proved to be an invaluable aid that complemented the standard pathologic
      examination of the brain and spinal cord. The compelling advantages of this
      postmortem radiographic procedure included the three-dimensional aspects of the
      images; the ability to detect mineral (ie, iron) deposits; small focal lesions
      such as hemorrhages or infarcts; and the ability to evaluate the extent of
      cerebral edema. For the same reasons, as well as its archival potential for
      documenting the topographic distribution of pathologic processes, this technique
      has great promise for forensic cases. High field-strength (7.0-T) imaging brought
      the resolution of magnetic resonance to the microscopic level and reaffirmed the
      potential value of magnetic resonance imaging for diagnostic and investigative
      studies in which both the histologic and fine radiologic features of lesions are
      of interest.

PMID- 8135625
TI  - Varying grades of epithelial atypia in the pancreatic ducts of humans.
      Classification based on morphometry and multivariate analysis and correlated with
      positive reactions of carcinoembryonic antigen.
AB  - To establish an adequate statistical classification of epithelial atypia in the
      pancreatic duct, a total of 78 areas of duct epithelia with varying grades of
      atypia were subjected to nine-parameter morphometry and nine-dimensional
      multivariate cluster analysis. The material was derived from 53 pancreases
      resected for various epithelial tumors or acute or chronic pancreatitis. The
      result was correlated with immunohistochemical findings in which the pattern of
      intraepithelial distribution of carcinoembryonic antigen changed with the degree
      of ductal atypia. Finally, atypical cells classified by cluster analysis and
      immunohistochemistry were subjected to computer-aided three-dimensional mapping
      to visualize their distribution in the ductal tree. Cluster analysis demonstrated
      that the various epithelial forms were classifiable into Clusters 1, 2, and 3,
      representing ordinary epithelia and mild and severe dysplasias, respectively. The
      last category was created so as to include not only in situ and invasive
      carcinoma but the so-called borderline atypical lesions. The reproducibility of
      this classification was proved by two sorts of discriminant analyses. Also, the
      grades of atypia shown by the clustering proved to correlate with the reaction
      patterns for carcinoembryonic antigen. In the computer-aided three-dimensional
      mapping, severely dysplastic areas were shown surrounded by zones of mild
      dysplasia, justifying the assumption of a stepwise carcinogenesis in the
      pancreatic ducts.

PMID- 8135626
TI  - Biochemically estrogen receptor-negative, progesterone receptor-positive breast
      carcinoma. Immunocytochemical hormone receptors and prognostic factors.
AB  - The significance of breast carcinomas biochemically negative (-) for estrogen
      receptor (ER), but positive (+) for progesterone receptor (PR), is poorly
      understood. It has been proposed that these tumors, more common in younger women,
      contain ER whose presence is masked in a biochemical binding assay by endogenous
      estrogen. Such tumors should be positive for ER by immunocytochemical assay. In a
      series of 319 tumors, 18 (5.6%) were biochemically ER-PR+. Patient age in this
      group (mean age, 59 years; range, 36 to 89 years) was slightly, but not
      significantly, lower than in patient groups with other receptor profiles. Only
      two (11%) of the 18 tumors were ER+ by immunocytochemical assay, not higher than
      the immunocytochemical ER positivity rate of seven (13%) of 62 biochemically ER
      PR- tumors in the same series. Progesterone receptor was positive by
      immunocytochemistry in nine (50%) ER-PR+ tumors, lower than the rate in
      biochemically ER+PR+ tumors (158 [87%] of 181). The tumor size, histologic tumor
      grade, and S-phase fraction showed trends to be higher in biochemically ER-PR+
      tumors than in ER+PR+ tumors. Biochemically ER-PR+ breast carcinomas are
      biologically different from ER+PR+ tumors.

PMID- 8135627
TI  - Signet-ring cell variant of invasive lobular carcinoma of the breast. A
      clinicopathologic study of 11 cases.
AB  - In signet-ring cell carcinoma of the breast, which was recognized in 1976 as a
      distinct clinicopathologic variant of lobular carcinoma, more than 20% of the
      malignant cells appear as signet rings formed by mucin-positive intracytoplasmic
      vacuoles. Several recent studies have demonstrated that the neoplasm behaves
      aggressively and is associated with a poor prognosis. However, the literature
      lacks information concerning steroid hormone receptor assays and DNA ploidy
      profiles, especially regarding how these tests affect a patient's prognosis.
      During a 5-year period (1985 to 1990), 11 (8.7%) of 126 cases of invasive lobular
      carcinoma met the criteria for signet-ring cell carcinoma. Ten of 11 cases were
      positive for estrogen and progesterone receptors; six cases showed type I and
      five showed type III DNA histograms. The high incidence of positive hormone
      receptors is significant: patients with receptor positive tumors, even those with
      type III DNA histograms, who were treated with tamoxifen citrate therapy after
      surgery had a significant increase in disease-free survival (30 months). Both the
      pathologist and the clinician should be aware of the prognostic influence of
      hormone receptor studies in the management of signet-ring cell carcinoma of the
      breast.

PMID- 8135628
TI  - Synovial metaplasia of a periprosthetic breast capsule.
AB  - A 48-year-old woman presented for reconstruction mammoplasty 5 years after
      undergoing a mastectomy for breast carcinoma. She underwent tissue expansion,
      with subsequent placement of a permanent silicone implant, removal of the
      permanent implant because of asymmetry, and further tissue expansion for another
      attempt at permanent silicone implant placement. The periprosthetic breast
      capsule surrounding the initial permanent implant consisted of a lining intima,
      subintima, and fibrous capsule consistent with synovium on light microscopy,
      immunohistochemical studies, transmission electron microscopy, and scanning
      electron microscopy. Silicone was localized intracellularly within the lining
      cells and extracellularly within the fibrous capsule by electron probe
      microanalysis. We believe that this case represents synovial metaplasia of a
      periprosthetic breast capsule that was most likely induced by repeated
      manipulation and silicon exposure from silicone gel leakage and the prosthetic
      Silastic shell.

PMID- 8135629
TI  - Immunocytology of body cavity fluids. MOC-31, a monoclonal antibody
      discriminating between mesothelial and epithelial cells.
AB  - This study was designed to assess whether monoclonal antibody MOC-31, which
      recognizes a membrane glycoprotein of 40-kd molecular weight present on
      epithelial cells and not on mesothelial cells, is a useful adjunct in the
      differential diagnosis of reactive pleural or ascitic fluids and adenocarcinoma.
      A panel of antibodies against carcinoembryonic antigen, epithelial membrane
      antigen, vimentin (antivimentin), keratin 18 (RGE-53), and cytokeratins of
      several molecular weights (AE1/AE3) was employed for comparison. Ninety-eight
      cases were selected based on the availability of pleural and peritoneal biopsy
      specimens for histologic confirmation. All cases with adenocarcinoma stained MOC
      31 positive, including three cases that had not been identified by morphologic
      criteria. All cases of reactive mesothelial hyperplasia were negative, as well as
      five cases of malignant mesothelioma. One case of squamous cell carcinoma was
      also negative. Anti-carcinoembryonic antigen only identified half of the
      carcinoma cases, and anti-epithelial membrane antigen and both anticytokeratin
      antibodies were positive in the majority of tumor cells as well as in the
      mesothelial cells. This study indicates that monoclonal antibody MOC-31 is a
      highly sensitive and reliable reagent in the differential diagnosis between
      mesothelial and epithelial cells.

PMID- 8135630
TI  - Hodgkin's disease with coexistent Castleman-like histologic features. A report of
      three cases.
AB  - We report three cases of Hodgkin's disease with coexistent histologic features
      reminiscent of Castleman's disease. In each case, reactive follicular hyperplasia
      was prominent and lymphoid follicles contained normal- or small-sized germinal
      centers. In two lesions, sheets of mature plasma cells and vascular proliferation
      were present in the interfollicular region, and some of the follicle centers were
      small, relatively depleted of lymphoid cells, and surrounded by concentric layers
      of small lymphocytes (so-called onionskin layers). However, unequivocal hyaline
      vascular lesions were absent. Both cases were referred with the diagnosis of
      Castleman's disease, most consistent with the plasma cell variant. Subsequent
      review demonstrated scattered Reed-Sternberg and Hodgkin cells in the
      interfollicular region, highlighted by immunohistochemical studies, and the
      diagnosis of interfollicular Hodgkin's disease was made. In the third lesion, the
      majority of the lymph node was replaced by Hodgkin's disease, nodular lymphocyte
      predominance subtype. In the regions not involved by tumor, reactive lymphoid
      follicles with hyaline-vascular lesions were numerous. This case was also
      referred with the diagnosis of Castleman's disease, of the hyaline-vascular type.
      We report these lesions to emphasize that histologic features reminiscent of
      Castleman's disease may occur in lymph nodes involved by Hodgkin's disease,
      resulting in diagnostic confusion. Castleman-like histologic features may
      represent a nonspecific immune response to a variety of immunologic stimuli
      including, as in these cases, the presence of Hodgkin's disease. The possibility
      of Hodgkin's disease needs to be considered and excluded before the diagnosis of
      Castleman's disease is made.

PMID- 8135631
TI  - Intracytoplasmic lumina in a case of bilaterally multifocal renal oncocytomas.
AB  - We report a case of bilaterally multifocal renal oncocytomas in a patient with
      chronic renal disease and a long history of hypertension. Histologic study of the
      multiple oncocytic neoplasms with hematoxylin-eosin, periodic acid-Schiff,
      trichrome, and colloidal iron stains revealed novel, intracytoplasmic lumina,
      which were accentuated by immunoperoxidase staining with high-molecular-weight
      cytokeratin, epithelial membrane antigen, and Arachis hypogaea lectin.
      Ultrastructural studies demonstrated multiple microvilli lining the
      intracytoplasmic lumina. We also review the literature on bilaterally multifocal
      oncocytomas.

PMID- 8135632
TI  - Thymofibrolipoma. A histologic variant of thymolipoma.
AB  - We report two cases of a thymic neoplasm showing abundant fibroconnective tissue
      with focal areas of fatty tissue. The two patients, a 9-year-old girl and a 32
      year-old man, were found to have an anterior mediastinal mass on routine chest
      roentgenograms. Surgical resection was performed in both cases. Because of the
      histologic features shown by these neoplasms, we believe that these cases
      represent a variant of thymolipoma, and we have named it thymofibrolipoma.

PMID- 8135633
TI  - Multiple ileal carcinoids and appendiceal endocrine carcinoma in association with
      Meckel's diverticulum. A histochemical and immunohistochemical study.
AB  - An unusual case of multicentric ileal carcinoids and appendiceal endocrine
      carcinoma in association with Meckel's diverticulum was studied, with special
      attention given to the histogenesis of these neoplasms. A total of six ileal
      carcinoids, the largest of which was located in the wall of Meckel's
      diverticulum, were macroscopically and microscopically confirmed to be
      multicentric and revealed no visceral metastases. The histochemical and
      immunohistochemical profiles of the ileal carcinoids and the appendiceal
      carcinoma differed considerably: the former resembled subepithelial
      neuroendocrine cells and the latter resembled epithelial nonmucous cells and
      Paneth cells. The appendiceal carcinoma exhibited signs of endocrine
      differentiation, expressing somatostatin and vasoactive intestinal polypeptide,
      and secreted mucus. The tumor had metastasized to various organs. The carcinoids
      exhibited signs of neuroendocrine and glandular differentiation, expressing
      neuron-specific enolase, serotonin, chromogranin A, and endocrine granule
      constituent, and secreted little mucus. The data suggest different tumor cell
      origins or different grades of differentiation of the two types of intestinal
      endocrine cell tumor.

PMID- 8135634
TI  - Ischemic changes in fetal myocardium. An autopsy series.
AB  - It has been assumed that fetal myocardial necrosis is an uncommon event that
      occurs only under unusual circumstances. We studied random heart sections on 76
      fetal and perinatal autopsies from a 4-year period to determine the types and
      frequency of histologic abnormalities that occur in fetal myocardium. Vacuolar
      degeneration was extremely common (43% of stillbirths, 84% of live births) but a
      nonspecific finding. Ischemic changes, which are typically associated with
      coagulation necrosis, myofiber waviness, or contraction band necrosis, were seen
      in 21% of stillbirths and 32% of live births. In the majority of cases with
      histologic evidence of ischemic change, a combination of either contraction band
      necrosis, coagulation necrosis, and/or myofiber waviness was identified. Only
      rarely was any one of the abnormalities seen as an isolated feature. In only two
      autopsies were the ischemic changes identified in the initial autopsy report. We
      conclude that the histologic changes associated with ischemia that may represent
      myocardial necrosis are not uncommon and are frequently overlooked at autopsy.

PMID- 8135635
TI  - Use of immunostains to ABH blood group antigens to resolve problems in identity
      of tissue specimens.
AB  - Identification of contaminating tissue fragments as "floaters" is a common
      problem in surgical pathology. They may be introduced at several steps in the
      processing of specimens, and they are capable of causing interpretative
      consternation. Using immunohistochemistry with monoclonal antibodies to blood
      group isoantigens A, B, and H, we studied nine cases in which floaters were
      present. In five of the study cases, discordant blood group immunostains allowed
      identification of the artifactual tissue fragments. By chance, the other four
      specimens contained probable floaters from patients whose blood groups were
      concordant with those from whom the "native" tissue had been obtained. These
      results indicate that in some instances, blood group immunostains may resolve
      interpretative difficulties surrounding floaters. It is likely that application
      of immunostains, directed at additional blood group antigens, will extend the
      utility of this procedure.

PMID- 8135636
TI  - Establishment of the formalin-free surgical pathology laboratory. Utility of an
      alcohol-based fixative.
AB  - Concerns about the toxicity of formalin dictate the need for alternative methods
      of tissue fixation. Alcohol-based fixatives have been proposed as optimal for
      immunohistochemical and nucleic acid methods and may be useful for diagnostic
      light microscopy. We recently converted our surgical pathology laboratory from
      10% neutral buffered formalin to an alcoholic fixative (56% ethanol and 20%
      polyethylene glycol) and compared 100 consecutive cases after conversion with 100
      formalin-fixed cases prior to conversion. One representative slide from each case
      was reviewed independently by four pathologists without knowledge of the fixative
      employed. The quality of fixation of each case was graded (0, very poor; 1, below
      average; 2, average; and 3, above average) based on the subjective composite
      evaluation of seven morphological features: tissue architecture, cell borders,
      cytoplasm, nuclear contours, chromatin texture, red blood cell membranes, and
      uniformity of staining. No significant difference in the quality of fixation was
      observed, although the average score of the alcoholic fixative was slightly lower
      than that of the formalin (2.59 vs 2.74). Interobserver concordance was 74%.
      Advantages of the alcoholic fixative included elimination of carcinogenic vapors,
      more rapid fixation, greater stain avidity, elimination of enzyme predigestion in
      immunohistochemical studies, and simple and rapid disposal. Disadvantages
      included slightly increased viscosity, increased variability of tissue staining
      and nuclear shrinkage, artifactual pigment deposition in bloody specimens, and
      increased flammability risk. Alcohol-polyethylene glycol appears to be a
      satisfactory alternative to formalin in routine diagnostic surgical pathology.

PMID- 8135637
TI  - Focal polypoid ischemia of the colon: atheroemboli presenting as a colonic polyp.
AB  - Cholesterol emboli are known to imitate a variety of disease processes, thereby
      leading to delayed diagnosis. We describe a patient with a localized polypoid
      mass of the colon without endoscopic evidence of generalized ischemic colitis.
      Histologic evaluation revealed this polyp to be the result of localized ischemia
      with identifiable submucosal atheroemboli. Localized polyp formation appears to
      be a rare manifestation of atheroemboli; consequently, focal ischemia, caused by
      atheroemboli, should be added to the differential diagnosis of polyps of the
      colon.

PMID- 8135638
TI  - Malignant female adnexal tumor of probable wolffian origin with review of the
      literature.
AB  - Malignant female adnexal tumor of probable wolffian origin is distinctly rare. To
      my knowledge, only four other cases have been reported in the English literature.
      This article reports a malignant female adnexal tumor of probable wolffian origin
      of the right broad ligament with extensive metastases to the omentum in an 81
      year-old woman. The patient died 3 months after the diagnosis. The site and
      characteristic histologic features of the tumor and the absence of carcinoma of
      the ovaries, fallopian tubes, and uterus indicate that this tumor is of wolffian
      origin.

PMID- 8135639
TI  - Oncocytic mucoepidermoid carcinoma of the parotid gland.
AB  - Oncocytic mucoepidermoid carcinoma of the salivary gland is rare. We describe a
      60-year-old woman who presented with a slowly growing left parotid mass. The
      patient underwent a total parotidectomy, and her postoperative course was
      uneventful. The gland was enlarged and showed a partially cystic mass containing
      clear mucoid material. Microscopically, the entire mass showed variably sized
      cysts lined predominantly with oncocytes and a few mucous goblet cells.
      Histochemical stains for mitochondria, such as phosphotungstic acid-hematoxylin,
      confirmed the presence of oncocytes. The recognition of this variant is
      important, since most of the other primary oncocytic lesions of the salivary
      glands are benign. The tumor in this case is considered to be a low-grade
      carcinoma; therefore, complete surgical excision and long-term clinical follow-up
      are adequate management.

PMID- 8135640
TI  - Multiple lesions of intravascular papillary endothelial hyperplasia (Masson's
      lesions).
AB  - We recently encountered an elderly female patient with multiple, rapidly growing
      vascular lesions on her forearm. Histologic examination and immunoperoxidase
      studies were performed to identify cells present within the lesions. The growths
      proved to be intravascular papillary endothelial hyperplasia. Immunohistochemical
      studies showed these lesions to be proliferations of factor VIII+, factor XIIIa+,
      and CD34+ cells. Intravascular papillary endothelial hyperplasia lesions are
      growths that histologically can mimic angiosarcoma, especially when they are
      multiple. They appear to be proliferations of endothelial cells and also contain
      dermal dendrocytes. This finding raises the question as to the exact origin of
      the cells that give rise to these tumors.

PMID- 8135641
TI  - [Antimycobacterial indole derivatives].
AB  - 1,3-Dinitro-2-(indol-3'-yl)-propanes 3 are synthesized by Michael reaction of
      nitromethane with the indolylnitroethenes 2. Reaction of the aldehydes 4 and 10
      with the benzylamines 12 as well as the reaction of the indolylalkylamines 6a and
      9a with the benzaldehydes 11 lead to Schiff bases which are reduced to N-benzyl
      (indol-3-ylmethyl)-amines 13 and N-benzyl-(indol-3-ylethyl)-amines 14,
      respectively; tert amines 16 are synthesized via the formamides 15, amines 18 are
      prepared according to Mannich. Inhibitory effects on Mycobacterium tuberculosis H
      37 Ra are investigated, a structure-activity relationship is discussed.

PMID- 8135642
TI  - [Actions of new iminium compounds against bacteria and fungi. 30. 3-alkoxymethyl
      1-hexyl-, 3-alkylthiomethyl-1-hexyl-, 3-alkoxymethyl-1-octyl- and 3
      alkylthiomethyl-1-octylbenzimidazolium chlorides].
AB  - Syntheses and antimicrobial activity of the title compounds are described. They
      were obtained by reaction of 1-hexyl- or 1-octylbenzimidazol with
      chloromethylalkyl ether or chloromethylalkyl sulfide. The antibacterial
      properties were tested on 13 strains of bacteria and fungi. The best
      antibacterial activity was exhibited by chlorides with octylthiomethyl and
      decyloxymethyl groups.

PMID- 8135643
TI  - beta-Carboline alkaloids, V: Total synthesis of the antimicrobial marine alkaloid
      eudistomin T.

PMID- 8135644
TI  - Synthesis of N-(9H-xanthen-9-yl)aminoalkanamide and N-(9H-thioxanthen-9
      yl)aminoalkanamide derivatives and their in vitro evaluation as potential
      intercalators and antitumor drugs.
AB  - A series of new N-(9H-xanthen-9-yl)aminoalkanamide and N-(9H-thioxanthen-9
      yl)aminoalkanamide derivatives was synthesized and evaluated as potential
      intercalators by measuring their DNA binding affinity. They were also tested for
      cytotoxic activity against L1210. The results suggest that the cytotoxicity of
      these molecules was not due to an intercalating mechanism.

PMID- 8135645
TI  - Selectivity of sterically fixed tryptamine and 5-methoxytryptamine derivatives
      for serotonin receptor subtypes, I: Synthesis of N-alkyl- and N,N-dialkyl-3
      indolylbicyclo[2.2.1]heptane-2-amines.
AB  - Twenty-six title compounds with the ethylamine part of tryptamine or 5
      methoxytryptamine fixed in an anticlinal ecliptic conformation were synthesized
      for assaying them at the different known serotonin receptors. Several alkylation
      methods have been improved and adapted for the space consuming norbornane system.
      The structures were fully elucidated by high-field NMR spectroscopy. All 1H- and
      13C-signals could be assigned by means of 1H-1H- and 13C-1H-correlation
      spectroscopy (COSY).

PMID- 8135646
TI  - Synthesis of antitumour carbon-bridged imidazopyridazine carbamates.
AB  - Two carbon-bridged analogues 11 and 15 of the potent microtubule inhibitor
      BW1069C85 (1) have been synthesised and evaluated for antitubulin and antitumour
      activity in vitro. Though the compounds were somewhat less potent than BW1069C85,
      significant activity against tubulin polymerisation and cell proliferation was
      demonstrated in the assays.

PMID- 8135647
TI  - [Lipoxygenase inhibitors. 3. Synthesis of tetrahydrobenzazepinone
      phenylhydrazones].
AB  - Tetrahydro-2H-benz[b]azepin-2-ones as starting substances are synthesized by
      Beckmann rearrangement of Schmidt reaction. The tetrahydrobenzazepinones are
      transformed into the thiones, thiolactim ethers and phenylhydrazones. The
      compounds are tested as inhibitors of soja lipoxygenase.

PMID- 8135648
TI  - Deviance as history: the future of perversion.
AB  - An approach to the social construction of concepts of sexual deviance and sexual
      perversions is considered. Deviance is conceptualized as a problem of control,
      perversion a problem of desire. These are seen as related to the larger sexual
      and nonsexual discursive practices of society and given to change as these
      contextualizing practices change. Changing conceptions regarding masturbation,
      homosexuality, pedophilia, and sadomasochism are examined.

PMID- 8135649
TI  - Comments on discordant monozygotic twinning in homosexuality.

PMID- 8135650
TI  - Intersexuality and the diagnosis of gender identity disorder.
AB  - Problems of gender identity development are the core concern in the psychosocial
      management of medical conditions involving ambiguous genitalia. This report
      discusses the difficulties encountered in applying the DSM category and criteria
      of Gender Identity Disorder (GID) to such patients. Data on prevalence, age of
      onset or presentation, sex ratio, and associated or predictive factors also
      suggest marked differences between intersex patients with gender identity
      problems and nonintersex patients with GID. Patients with intersexuality or
      similar medical conditions should be excluded from the GID diagnosis.

PMID- 8135651
TI  - Effects of repeated questionnaire administration in longitudinal studies of
      adolescent males' sexual behavior.
AB  - By comparing four similar groups of young adolescent males who completed
      questionnaires about their sexual behavior different numbers of times at various
      intervals, we explore the hypothesis that repeated questionnaire completion will
      affect sexual behavior. We find little support for the hypothesis even when the
      number of questionnaire administrations is very high.

PMID- 8135652
TI  - Relationships among cardiovascular, muscular, and oxytocin responses during human
      sexual activity.
AB  - To determine the psychophysiological correlates of hormonal response during
      sexual activity, systolic blood pressure (SBP), anal electromyography (EMG), and
      anal photoplethysmography (APG) were monitored continuously throughout testing in
      13 women and 10 men. Each subject completed two or more tests of self-stimulation
      to 5 min beyond orgasm. Blood samples were obtained continuously for measurement
      of oxytocin (OT) levels. In both men and women, very high positive correlations
      were observed between the percentage change in levels from baseline through
      orgasm of: OT and SBP; OT and EMG intensity prior to and during orgasm; APG and
      EMG. The number of anal contractions and duration of orgasm were also highly
      correlated. Two patterns of orgasm were defined by the presence or absence of a
      quiescent period between orgasmic contractions. EMG and APG amplitudes correlated
      with the pattern of orgasm. Subjective orgasm intensity correlated significantly
      with increased levels of OT in multiorgasmic women only. The positive
      correlations between measures are consistent with a possible functional role for
      OT in human sexual response.

PMID- 8135653
TI  - False rape allegations.
AB  - With the cooperation of the police agency of a small metropolitan community, 45
      consecutive, disposed, false rape allegations covering a 9 year period were
      studied. These false rape allegations constitute 41% the total forcible rape
      cases (n = 109) reported during this period. These false allegations appear to
      serve three major functions for the complainants: providing an alibi, seeking
      revenge, and obtaining sympathy and attention. False rape allegations are not the
      consequence of a gender-linked aberration, as frequently claimed, but reflect
      impulsive and desperate efforts to cope with personal and social stress
      situations.

PMID- 8135654
TI  - Men pressured and forced into sexual experience.
AB  - A predominantly heterosexual sample of 204 college men were asked to report
      incidents of pressured or forced sexual touch or intercourse since age 16. About
      34% indicated they had received coercive sexual contact: 24% from women, 4% from
      men, and 6% from both sexes. Contact involved only sexual touching for 12% and
      intercourse for 22%. Sexual contact was pressured in 88% of the 81 reported
      incidents by tactics of persuasion, intoxication, threat of love withdrawal, and
      bribery. In 12% of the incidents, sexual contact was forced through physical
      restraint, physical intimidation, threat of harm, or harm. Contact was initiated
      by an acquaintance or intimate in 77% of incidents. The negative emotional impact
      of male contact was rated significantly higher than the impact of female contact.
      Men with and without coercion experience did not differ, however, for scale
      scores on sexual esteem, depression, and preoccupation. Interviews with 10
      subjects revealed complex reactions to coercive male and female contact,
      including doubts about one's sexuality, resentment of unexpected or forceful
      contact, and fear of telling others about the event.

PMID- 8135655
TI  - Toxicokinetics of diethylene glycol (DEG) in the rat.
AB  - Oral doses of 1 and 5 ml/kg 14C-diethylene glycol (DEG) given to rats were
      rapidly and almost completely absorbed, the invasion constants being 2.95 h-1 and
      4.24 h-1. The kinetics of invasion were determined with the method of residuals
      (Rowland and Tozer 1989) and by reconstruction of the invasion curves according
      to Kubler (1970). 14C-DEG was rapidly distributed from the blood into the organs
      and tissues in the order kidneys > brain > spleen > liver > muscle > fat, i.e.
      the same order as the blood flow. The relative volume of distribution, app. VD,
      was determined at 298 ml, indicating distribution over the whole body. After oral
      doses of 1, 5, and 10 ml 14C-DEG/kg 64, 87, and 91% of 14C activity in rat blood
      disappeared in 12-16 h with a half-life of 3.4 h and the remaining 9, 5, and 4%
      with half-lives of 39 h, 45 h, and 49 h. A total of 73-96% of 14C activity in
      blood was excreted with the urine and 0.7-2.2% with the faeces. From the
      cumulative urinary excretion kinetics half-lives of 6 h were determined for doses
      of 1 and 5 ml/kg and 10 h for the dose of 10 ml/kg. After doses of 5 ml/kg and 10
      ml/kg 14C-DEG semi-logarithmic plots of elimination rate versus time were
      constant for 5 and 9 h, respectively, indicating that DEG accelerated its renal
      elimination by inducing osmotic diuresis. Thereafter urinary excretion followed
      first order kinetics with elimination half-lives of 3.6 h. After oral doses of 5
      ml/kg 14C-DEG given to rats of 336 g body weight with an app. VD of 297 ml, the
      total clearance of 14C activity was determined at 63 ml/h, and the renal
      clearance of unmetabolized DEG was 66 ml/h. The ratio of ClDEG to Cl(inulin) =
      0.64 indicated that DEG and its metabolite 2-hydroxyethoxyacetate (2-HEAA) were
      reabsorbed from the tubuli into the blood capillaries. DEG produced metabolic
      acidosis, which was completely balanced after doses of 1 and 5 ml/kg, but doses
      greater than 10 ml/kg produced non-compensated metabolic acidosis, hydropic
      degeneration of the tubuli, oliguria, anuria, accumulation of urea-N, and death
      in uraemic coma.

PMID- 8135656
TI  - Effect of subchronic administration of antioxidants against cigarette smoke
      exposure in rats.
AB  - Effects of subchronic administration of antioxidants against pulmonary damage
      mediated by cigarette smoke were investigated in rats. Rats were continuously
      received ascorbic acid, N-acetylcysteine and ginseng extract together drinking
      water from day 25 after birth. After 30 days of antioxidant supplementation, rats
      were exposed to cigarette smoke generated from six cigarettes (11 mg tar) for 20
      min per day throughout 30 days, and then several biochemical markers related to
      the redox status in vivo were analyzed in the respiratory system. The cigarette
      smoke induced mild histological changes in trachea and lungs. The activity of
      superoxide dismutase (SOD) in the lung was significantly increased, and catalase
      and glutathione peroxidase activities were increased less than SOD, but total
      sulfhydryl compounds (Total-SH) content was decreased by cigarette smoking. In
      spite of the increase in activities of antioxidant enzymes, the inhibitory
      capacity of lung preparations on in vitro lipid peroxidation using ox brain
      homogenates was decreased and the change in the capacity was not related to the
      changes of these intracellular enzymes activities, but with the content of Total
      SH. On the other hand, the content of thiobarbituric acid reactive substances and
      the ratio of elastase to anti-protease in the lung homogenates were significantly
      increased. Supplementation of antioxidants, however, effectively attenuated all
      of such alterations induced by cigarette smoke. These results indicate that
      although cigarette smoking induces antioxidant enzymes in the lung as a self
      defense mechanism, it seems to be not sufficient to protect the pulmonary system,
      and that chronic antioxidant feeding could be effective to reduce pulmonary
      damage induced by free radicals.

PMID- 8135657
TI  - Cytotoxicity of menadione and related quinones in freshly isolated rat
      hepatocytes: effects on thiol homeostasis and energy charge.
AB  - The cytotoxic events in freshly isolated rat hepatocytes following exposure over
      2 h to menadione (2-methyl-1,4-naphthoquinone) and two closely related quinones,
      2,3-dimethyl-1,4-naphthoquinone (DMNQ) and 1,4-naphthoquinone (NQ), were
      examined. These quinones differ in their arylation capacity (NQ > menadione >>
      DMNQ) and in their potential to induce redox cycling (NQ approximately menadione
      >> DMNQ) The glutathione status (reduced and oxidized glutathione) of the
      hepatocytes was determined using HPLC after derivatization with monobromobimane.
      Protein thiols were measured spectrophotometrically and the energy charge of the
      cells was determined with HPLC using ion pair chromatography. The leakage of
      lactate dehydrogenase was used as a marker for cell viability. All three quinones
      caused alterations of the glutathione status of the exposed cells but the effects
      were markedly different. Exposure to DMNQ resulted in a slow decrease of reduced
      glutathione and an increase of mixed disulfides. The other two quinones caused an
      almost complete depletion of reduced glutathione within 5 min. Hepatocytes
      exposed to NQ accumulated oxidized glutathione whereas menadione-exposed
      hepatocytes showed increased levels of mixed disulfides. We did not find any
      effects of DMNQ (200 microM) on protein thiols, energy charge or cell viability.
      There was a clear difference in the effects of menadione and NQ on protein
      thiols, energy charge and cell viability; exposure to NQ resulted in a more
      extensive decrease of protein thiols and energy charge and an earlier onset of
      lactate dehydrogenase leakage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135658
TI  - Glutathione dependent detoxication in adult rat hepatocytes under various culture
      conditions.
AB  - In order to obtain more information concerning the effects of culture and medium
      conditions on the glutathione dependent detoxication system in hepatocyte
      cultures, glutathione reductase (GR) and glutathione peroxidase (GPx) activities
      were studied in both pure cultures of adult rat hepatocytes and their co-cultures
      with rat epithelial cells. Cells were isolated either with an oxygen saturated
      Krebs Henseleit buffer (KHB) or with a non-gassed Hepes buffer. As medium
      conditions, additions of 10% fetal calf serum (FCS), 25 mM nicotinamide, 0.1
      microM selenium and 2% dimethylsulphoxide, respectively, to the culture medium
      were examined. It was found that co-cultures of rat hepatocytes can cope better
      with oxidative stress than pure cultures do. This conclusion was reached from the
      following observations. When oxygenated KHB was used as isolating buffer, GR and
      GPx activities increased during the first days of pure culture and then slowly
      decreased. This was observed for all the medium conditions studied and no
      significant differences between the different media could be observed. For co
      cultures, however, after some initial variations GR and GPx activities reached
      stabilized levels which were not only significantly lower than those observed for
      pure cultures, but were also maintained throughout the whole culture period.
      Supplementation of the medium had no effect on these findings with the exception
      of high GPx activities when Se was added to the co-culture medium. When Hepes
      buffer with a low oxygen content was used in cell isolation, pure cultures showed
      significantly lower GR and GPx activities than those first mentioned.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8135659
TI  - Carbon tetrachloride-induced alterations in hepatic glutathione and ascorbic acid
      contents in mice fed a diet containing ascorbate esters.
AB  - The effects of L-ascorbyl stearate and L-ascorbyl palmitate on carbon
      tetrachloride-induced alterations in glutathione and ascorbic acid content in
      mouse livers were investigated. Powdered food containing 1% ascorbate ester was
      given to mice for 3 days before and 1 day after a single injection of CCl4 (0.1
      ml/kg, i.p.). Biochemical parameters were determined 1 day after the CCl4
      administration. The ascorbate esters markedly attenuated CCl4-induced alterations
      such as reductions in ascorbate content and hepatic glutathione S-transferase
      (GST) activity, and increases in glutathione and calcium content and serum GST
      activity. The CCl4-induced rise in thiobarbituric acid-reactive substances, an
      index of lipid peroxidation, was not affected by ascorbate feeding. These
      findings suggest that exogenous ascorbate, in addition to endogenous glutathione,
      is available to maintain the intracellular milieu in a reduced state, and that
      this system operates more effectively in aqueous compartments than in membrane
      lipid bilayers.

PMID- 8135661
TI  - Effect of pretreatment with CBDP on the toxicokinetics of soman stereoisomers in
      rats and guinea pigs.
AB  - Pretreatment of rats and guinea pigs with the specific carboxylesterase inhibitor
      2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) reduces the LD50 of the
      nerve agent C(+/-)P(+/-)-soman in these species to the same range as in primates.
      This suggests that such CBDP-pretreated animals can be used in investigations
      that are relevant for prophylaxis and therapy of intoxication with C(+/-)P(+/-)
      soman in primates including humans. In order to test this hypothesis we have
      studied the toxicokinetics of the toxic C(+/-)P(-)-isomers of soman in
      artificially respirated and CBDP-pretreated rats and guinea pigs at intravenous
      doses corresponding to 6x LD50. A comparison of the areas under the curve (AUCs)
      of the blood levels of C(+/-)P(-)-soman in pretreated and non-pretreated animals
      at the same absolute dose shows extreme nonlinearity with dose, indicating that
      CBDP occupies highly reactive binding sites which are no longer available for
      sequestration of the soman isomers. The AUCs of C(+/-)P(-)-soman at equitoxic
      doses of 6x LD50 are reduced by pretreatment with CBDP from 1683 to 464 ng.min.ml
      1 in rats and from 978 to 176 ng.min.ml-1 in guinea pigs, which is in the range
      of the AUC in non-pretreated marmosets at an equitoxic dose (419 ng.min.ml-1).
      The blood levels of the C(+/-)P(-)-isomers in marmosets and CBDP rats are rather
      similar during the first 7 min, but persist in CBDP rats for 2 h longer at
      toxicologically relevant levels than in marmosets.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8135660
TI  - Modulation of procainamide toxicity by selenium-enriched yeast in rats.
AB  - Free radical processes are proposed to play a crucial role in the development of
      procainamide adverse effects. Therefore, selenium, as a potent antioxidant, may
      modified procainamide toxicity. To test this hypothesis plasma and liver
      thiobarbituric acid-reacting substances (TBARS), plasma antioxidant activity
      (AOA), erythrocyte and liver superoxide dismutase (SOD), catalase, as well as
      selenium-dependent glutathione peroxidase (Se-GPX) were determined in the
      following four groups of rats: selenium-treated (Se), procainamide-treated (P),
      procainamide and selenium-treated (P + Se), and control (C). Morphological
      studies of leukocytes [tested for lupus erythematosus (LE) cells] and liver were
      also made. Atypical, i.e. enlarged and swollen, leukocytes resulting from
      procainamide and selenium treatment were observed. These changes were found in
      four out of five rats in the Se group, eight out of ten in the P group, and in
      seven out of ten in the P + Se group. LE-like cells were observed in two rats in
      the P + Se group. A statistically significant decrease in plasma and liver TBARS
      by 20% and 36%, respectively, increased activity of SOD by 20%, catalase by 48%
      and Se-GPX by 15% in erythrocytes, and decreased activity of liver SOD by 17% and
      catalase by 22% were found in the P + Se group as compared to the P group. These
      results indicated that selenium exerted antioxidant effects on the procainamide
      treated rats. However, selenium did not prevent the development of disturbances
      in leukocyte morphology, on the contrary, it possibly promoted the conversion of
      leukocytes to LE cells.

PMID- 8135662
TI  - Dose-DNA adduct relationship for ethylene oxide.

PMID- 8135663
TI  - [Comparative study of health problems between wives of alcoholics and control
      wives].
AB  - This study involves an the analysis of health problems and psychosomatic
      disorders between wives of alcoholics and those of non-alcoholics. The subjects
      of the study were 122 wives of alcoholics who accompanied their husbands for
      outpatient alcoholism treatment at Kurihama National Hospital. For an appropriate
      comparison, 88 aged-matched wives of non-alcoholic husbands were asked to
      cooperate as controls. The subjects were given Cornell Medical Index (CMI) and
      our original questionnaire on their own and their husbands' health problems on
      their first outpatient visit. The controls were also given them during the same
      research period. The results are briefly summarized as follows: 1. The most
      obvious health problem of wives of alcoholics with an incidence significantly
      higher than that of wives of non-alcoholics was genital disease; 13.9% of the
      subjects had such diseases, in contrast to 1.1% of the controls. 2. The second
      health problem of the subjects which significantly exceeded that of the controls
      was cardiovascular disease (9.0% vs 1.1%). 3. The mean number of past illnesses
      of the subjects was 0.78 (SD 1.08) compared with 0.51 (SD 0.82) for the controls.
      4. The rate of current illness of the subjects was 28.2% compared with 19.3% for
      the controls. 5. The rate of CMI Category IV (indicates "neurotic") of the
      subjects was 5.0% compared with 0.0% for the controls. 6. As a whole, our results
      were more moderate than those of previous studies, but wives of alcoholics had
      more current and past illness, and were more neurotic than the controls.

PMID- 8135664
TI  - [Concentrations of ethanol and ethanol metabolites and symptoms of acute alcohol
      intoxicated patients].
AB  - Five patients who presented to an emergency room and did not have other injury
      and disease with acute alcohol intoxication were analyzed about blood and urine
      ethanol, acetaldehyde, acetate and acetone levels. The average concentrations of
      ethanol, acetaldehyde, acetate and acetone in blood were 37.0 mM (1.7 mg/ml), 18
      microM, 1.00 mM and 18 microM, respectively and the concentrations in urine were
      50.8 mM (2.3 mg/ml), 37 microM, 0.79 mM and 47 microM, respectively. Clinical
      symptoms were concerned with both ethanol concentration and concentrations of
      ethanol metabolites. Their symptoms of acute alcohol-intoxicated patients were
      caused by the ethanol concentrations which was less than the levels reported in
      early studies.

PMID- 8135665
TI  - [Withdrawal characteristics following frequent intravenous administration of
      several opioids in rats].
AB  - Characteristics of withdrawal signs of several opioids were compared in rats
      after short-term frequent intravenous infusions. Male Sprague-Dawley rats with
      catheters implanted in the jugular veins were infused with a fixed dose of a drug
      hourly for 72 hrs. Thirty min after the final infusion, naloxone 4 mg/kg, s.c.
      was administered and withdrawal signs were observed for 1 hr and the severity of
      the withdrawal signs was scored, classified into a behavioral sign score,
      autonomic sign score, and body weight loss score. As a result, total withdrawal
      scores of morphine, methadone, d-propoxyphene, loperamide, tramadol, and
      pentazocine were significantly higher than that of saline, with the highest score
      being observed for 4 mg/kg or more of morphine. The total score of
      ethylketocyclazocine was slightly but significantly higher than that of saline.
      Buprenorphine and thebaine produced no observable withdrawal signs. The
      behavioral sign score tended to be higher than the other 2 scores in the drugs
      showing relatively low but significant total scores such as tramadol,
      pentazocine, and ethylketocyclazocine, while the score of autonomic signs or the
      body weight loss tended to be higher in drugs showing high total scores. Thus, in
      the case of opioids, it is considered that the severity of withdrawal signs was
      mainly derived from the autonomic signs including diarrhea which may result in
      body weight loss.

PMID- 8135666
TI  - [A characteristic of alcoholics with the atypical aldehyde dehydrogenase
      (ALDH2(2)--a relationship to other alcohol metabolizing enzymes].
AB  - The series were composed of 59 alcoholics. All the subjects fulfilled the DSM-III
      R criteria for alcohol dependency. We investigated the genotype at ALDH2. 6
      patients were heterozygous ALDH2(1)/ALDH2(2). We determined the genotypes at
      ADH2, ADH3 and P-4502E1 about 6 patients. 5 patients had ADH2(1)/ADH2(1) allele.
      2 patients had P-450E1*C2. We found a genetic characteristic about alcoholics
      with the heterozygous ALDH2(1)/ALDH2(2) allele.

PMID- 8135667
TI  - [Relationship between alcoholism and genotypes of acetaldehyde-metabolizing
      enzymes].
AB  - The genotypes of the CYP2E1 and ALDH2 loci in alcoholic and non-alcoholic
      (healthy) Japanese were investigated to examine the relationship between the
      polymorphisms of CYP2E1 (C1/C2) and ALDH2 (ALDH2*1/ALDH2*2), and the
      susceptibility to alcoholism. There was no significant difference in C2 gene
      frequency between alcoholics (0.20) and non-alcoholics (0.19), while there was a
      significant difference in ALDH2 allele frequency, suggesting that the C2 allele
      of CYP2E1 may have nothing to the risk of developing alcoholism in Japanese,
      whereas the ALDH2*1 allele may influence drinking behavior and the development of
      alcoholism.

PMID- 8135668
TI  - Association between human in vitro fertilization rate and pregnancy outcome: a
      possible involvement of spermatozoal quality in subsequent embryonic viability.
AB  - A conventional view of mammalian fertilization is that the active component of
      the process: the spermatozoon, by virtue of its progressive motility and
      acrosomal enzymes, penetrates an otherwise passive oocyte. This concept has
      placed bias on spermatozoal normality as largely determining the outcome of
      fertilization; once this has been achieved then the contribution of the
      spermatozoon is often forgotten, and attention switches to the maternally derived
      "blue-print" for early embryonic development. Paternal genomic contribution is
      known to start at the eight-cell stage in the human, but this is usually after
      the time when early cleavage stage (2 to 8-cell stage) embryos are replaced in
      human assisted reproductive technologies (ART) procedures such as in vitro
      fertilization and embryo transfer (IVF-ET). Hence, fundamental abnormal
      contributions to embryogenesis derived from the fertilizing spermatozoon have
      often been ignored. Human IVF-ET has permitted far greater powers of analysis of
      the fertilization event, and fertilization success appears to be determined in
      such a system by three main factors: spermatozoal quality, oocyte quality, and
      quality of in vitro culture conditions (the gamete environment). If the second
      two factors are more carefully controlled than the first, as is the usual
      emphasis in routine human IVF practice, then any large variation in fertilization
      rates that are also significantly related to embryonic viability and ultimately
      pregnancy outcome, may be thought to be more directly associated with original
      quality of the fertilizing spermatozoon. An analysis of results of 758 IVF cases
      provides preliminary evidence to show that there is a close association between
      human in vitro fertilization rate and subsequent embryo viability following
      replacement. In accepting this hypothesis as a possibility, we should drastically
      change our attitude from one of the spermatozoon as a robust, simple initiator of
      embryonic development, and embrace the idea of the vulnerability of such germ
      cells both during and after their production, and how detrimental influences on
      this might profoundly affect embryogenesis after successful fertilization.

PMID- 8135669
TI  - Maximal cytoreductive surgery and high dose cisplatin chemotherapy for advanced
      ovarian cancer.
AB  - Fifty-eight stage III patients treated at The Jikei University Hospital were
      analysed retrospectively, in order to clarify the combination effect of maximal
      cytoreductive surgery and high dose cisplatin based chemotherapy in advanced
      ovarian cancer. They were divided into 4 groups by treatment they received which
      was as follows: Group A (n = 25); total abdominal hysterectomy (TAH), bilateral
      salpingooophorectomy (BSO) and omentectomy (OMTX) done at primary surgery and
      followed by 5 courses of "low dose" CAP therapy (cyclophosphamide 200 mg/sq m,
      adriamycin 20 mg/sq m, cisplatin 35 mg/sq m every 4 weeks for 5 courses). Group B
      (n = 4); TAH, BSO and OMTX carried out at primary surgery and followed by "high
      dose" CAP therapy (cyclophosphamide 200 mg/sq m, adriamycin 20 mg/sq m, cisplatin
      70 mg/sq m, every 4 weeks for 5 courses and every 8-12 weeks for 5 courses
      thereafter). Group C (n = 13) received TAH, BSO and OMTX at the primary operation
      and paraaortic and pelvic lymphadenectomy (LNX) at the second look operation
      (SLO) with "high dose" CAP therapy as did Group B. Group D (n = 16), TAH, BSO,
      OMTX, LNX with maximal efforts made to reduce the size of the residual tumor to
      less than 2 cm at the primary surgery followed by "high dose" CAP therapy. The 3
      year and 5 year survival rate of each group were as follows: Group A 15.6%,
      15.6%, Group B 25.0%, 0%, Group C 81.8%, 0% and Group D 50.8%, 38.1%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135670
TI  - Megacystis microcolon intestinal hypoperistalsis syndrome: antenatal ultrasound
      appearance. A case report.

PMID- 8135671
TI  - Serum level of magnesium attained in magnesium sulfate therapy for severe
      preeclampsia.
AB  - Serum magnesium levels were determined in severe preeclampsia patients who were
      treated with magnesium sulfate infusion. Forty-four patients with diagnosis of
      severe preeclampsia between 30-41 weeks gestation, given a conventional 5 g
      magnesium sulfate intravenous bolus infusion and 1 g/hr continuous infusion and
      continued 24 hours postpartum, were prospectively studied. The mean pre-treatment
      magnesium level was 2.3 +/- 0.3 mg/dl which was similar to those reports. The
      levels measured at 1/2, 1, 2, 4, 12 and 24 hours after initiation of magnesium
      infusion were 4.8 +/- 0.4, 4.7 +/- 0.4, 4.5 +/- 0.3, 4.7 +/- 0.3, 5.4 +/- 0.3 and
      5.9 +/- 0.3 mg/dl respectively. After delivery the levels were measured
      immediately, 12, and 24 hours and found to be 4.7 +/- 0.4, 4.9 +/- 0.4, and 5.2
      +/- 0.3 mg/dl respectively. The serum magnesium levels were also varied with
      maternal weight, the dose regimen used in our study is appropriate for Asian
      pregnant women whose body weight usually less than 70 kg.

PMID- 8135672
TI  - Relationship between the prognosis of conception and the location of pelvic
      involvement in endometriosis: significance of the TOP (tube, ovary, peritoneum)
      classification.
AB  - To determine the main factors that affect the prognosis for conception in
      endometriosis-associated infertility, 99 infertile patients with laparoscopically
      confirmed endometriosis were classified according to the new TOP classification,
      which we have developed to evaluate the severity of endometriosis by site, i.e.,
      fallopian tubes (T), ovaries (O) and the peritoneum (P). According to the TOP
      classification, a negative correlation between the pregnancy rate after treatment
      and the severity of lesions was noted in case of tubal and peritoneal
      involvement, but not when the ovaries were involved. If there was no tubal
      involvement or only unilateral tubal involvement, high pregnancy rates were
      achieved for patients with ovarian endometrioma (87%) and for those with partial
      or complete posterior cul-de-sac obliteration (83%). The results suggest that for
      endometriosis-associated infertility, the treatment modality should be selected
      according to the severity of tubal involvement, which is considered to contribute
      to infertility more than ovarian or peritoneal lesions.

PMID- 8135673
TI  - Changes of perinatal statistics in a semiurban setup between two time periods in
      Malaysia.
AB  - Hospital University Sains Malaysia (HUSM) functions as the state referral centre
      and the only hospital for the state of Kelantan that can offer neonatal intensive
      care service. The deliveries in HUSM with grand multiparity, late booking and
      problems of late referrals resembles a hospital serving a semiurban rather than
      an urban community. A comparison between the year 1989 and 1991 showed marked
      improvement of perinatal mortality rate from 41.32 to 24.88, which is
      significantly better than the improvement achieved from 1987 to 1989 (46.0 to
      41.32). This was possible due to a marked fall in the early neonatal mortality
      rate from 10.02 in 1989 to 5.45 in 1991 and fall in the stillbirth rate from
      31.61 to 19.53.

PMID- 8135674
TI  - Pregnancy after chemotherapy for trophoblastic diseases and psychosomatic
      development in the progeny.
AB  - We treated 542 patients with trophoblastic diseases from 1965 through 1988, and
      succeeded in preserving fertility in 269 of them (240 cases of invasive mole and
      29 cases of choriocarcinoma). Of the 269 patients, 198 (79.5%) conceived after
      completing treatment. A total of 396 pregnancies in these women resulted in 295
      term live births (74.5%), 51 spontaneous abortions (12.9%), and 4 recurrences of
      moles (1.0%). Four cases (1.32%) of malformations were discovered. The growth
      conditions of 101 children born in 1976 or later were followed up until the age
      of 18 months. Their heights or weights did not differ significantly from those of
      children measured in national infantile-growth surveys. The psychoneurological
      development of 54 children up to the age of 7 years who were studied by using
      infantile mental-development questionnaires showed no marked mental retardation.
      Our results provide strong evidence of the safety of chemotherapy for the
      treatment of trophoblastic diseases.

PMID- 8135675
TI  - Prediction of dystocia by entanglement (impaction) in vertex-vertex type twin
      delivery.
AB  - We studied the fetal position in vertex-vertex type twins in 6 impaction cases
      and in 23 cases of vaginal deliveries without impaction. The results obtained
      were as follows: (1) In 6 impaction cases, the presenting head of the first fetus
      was shown to be at the maternal pubic side and the head of the second fetus at
      the maternal sacral side. (2) In 23 cases without impaction, the presenting head
      of the first fetus was shown to be at the maternal sacral side and the head of
      the second fetus at the maternal pubic side. (3) There was a statistical
      significant difference between the 6 impaction cases and the 23 non impaction
      cases as determined by the Chi-square test (p < 0.001). Our study suggests that
      it is possible to predict the occurrence of impaction in vertex-vertex type twin
      deliveries by examining the positional relationship of the presenting heads of
      the first and second fetuses. There was a higher possibility of impaction when
      the head and body of twin 1 was located in the maternal-pubic position, while the
      head of twin 2 was in the sacral position. In contrast, impaction never occurred
      when the head and body of twin 1 was in the maternal-sacral position and the head
      of twin 2 was in the pubic position.

PMID- 8135676
TI  - Serum manganese superoxide dismutase (MnSOD) and histological virulence of
      ovarian cancer.
AB  - The serum level of a scavenging enzyme, manganese superoxide dismutase (MnSOD),
      was examined in 78 patients with ovarian cancer. Tumors included 27 stage I, 6
      stage II, 37 stage III and 8 stage IV diseases. They were classified as 43
      serous, 18 mucinous, 10 clear cell and 7 endometrioid neoplasms, and grouped into
      25 grade I, 27 grade II and 26 grade III cancers. Factors affecting the MnSOD
      level were estimated by analysis of variance and Bonferroni t-test. From these,
      both the stage and histology were less-effectively affected by the level, while
      the histological grade was estimated as effective with p < 0.05. The MnSOD value
      increased significantly in accordance with the escalation of the tumor grade with
      p = 0.02 for grade I vs II, 0.005 for II vs III, and 0.0001 for I vs III
      respectively. MnSOD determination may be unique as a predictor of the
      histological virulence of ovarian carcinoma.

PMID- 8135677
TI  - Prostaglandins biosynthesis in the rabbit uterine cervix at various stages of
      pregnancy.
AB  - The accumulation of prostaglandins (PGs: 6-keto PGF1 alpha, PGE2, PGF2 alpha and
      TXB2) elicited by A-23187, a Ca(2+)-ionophore, was studied in the uterine
      cervical tissue taken from non-pregnant and pregnant (10th, 20th and 30th day of
      pregnancy) rabbits in vitro. At every stage of pregnancy, the accumulation of PGs
      levels increased as follows; 6-keto PGF1 alpha, PGE2, PGF2 alpha and TXB2.
      Biosynthesis of each began to increase from the 20th day of pregnancy, and was
      significantly elevated at the 30th day. Especially, 6-keto PGF1 alpha and PGE2
      were remarkably higher than PGF2 alpha and TXB2 at term, and so they are thought
      to play a more important role in cervical dilation and ripening than the other
      PGs. Six-keto PGF1 alpha was significantly elevated on the 20th day, when other
      PGs had not yet began to increase. It is thus conceivable that PGI2 plays an
      important role in the predispositing of cervical ripening.

PMID- 8135678
TI  - Studies on the permeability and enzyme-cytochemistry of the mouse hemotrichorial
      placenta.
AB  - The permeability of higher molecular weight substances was investigated in mouse
      chorioallantoic labyrinthine hemotrichorial placenta, using horseradish
      peroxidase as a tracer. At the same time, ultrastructural localizations of some
      important enzymes, such as alkaline phosphatase (ALP), acid phosphatase (ACP),
      Ca(++)-ATPase and guanylate cyclase were elucidated in this organ by means of the
      enzyme-cytochemical technique. Peroxidase easily entered the space between layers
      I and II, and no penetration of this tracer beyond layer II was observed. The
      reaction products for ALP activity were found mainly on the maternal side of the
      plasma membrane of the layer II trophoblast. ACP activity was confined to the
      lysosomes of this layer II cell. In short, peroxidase stopped at the cell surface
      of the layer II trophoblast, and both ALP and ACP coexisted in this layer II
      cell. These observations strongly suggest that the layer II trophoblast,
      especially the surface plasma membrane of this cell, may have an important role
      in regulating the materno-fetal transfer of substances in mouse chorioallantoic
      placenta.

PMID- 8135680
TI  - Experimental studies of cis-diamminedichloroplatinum (II) and cis-diammine-1, 1
      cyclobutandicarboxylate platinum (II) combination therapy for malignant
      gynecologic tumors.
AB  - A comparative exploration of the optimum regimens for CDDP and CBDCA therapy of
      malignant gynecologic tumors was conducted using both in vitro and in vivo
      approaches. In vitro, CBDCA exerted less cytotoxicity with short-time exposure,
      but over a longer time was as effective as CDDP. Pharmacokinetic studies
      demonstrated rapid binding of all administered CDDP to protein, while free-Pt was
      seen for many hours after CBDCA treatment. These results suggest that the gradual
      action of CBDCA leads to the appearance of cytotoxicity, and that in clinical use
      CBDCA affects the tumor cells for a long time. To increase the active dose of
      platinum, treatment with high doses of CDDP, or CBDCA, or the two platinum
      compounds with different pharmacokinetic behavior in combination, was designed
      for optimal therapeutic protocols. In the CDDP-alone treatment animals, renal
      toxicity was apparent with the increase in dose level. However, in the
      combination CDDP-and-CBDCA treatment animals, the total dose level could be
      elevated without causing toxicity. In the drug-sensitivity test, the combination
      therapy also exerted strong activity. The fact that the combined CDDP-and-CBDCA
      therapy appears to exert greater anti-tumor effects without any increment in
      adverse toxicity of these drugs is clinically promising.

PMID- 8135679
TI  - Immunoradiometrical measurement of tissue polypeptide specific antigen (TPS) in
      normal, healthy, nonpregnant and pregnant Japanese women.
AB  - Using a monoclonal immunoradiometrical assay, we measured the concentrations of
      the specific epitope M3 of tissue polypeptide antigen (TPA), namely, tissue
      polypeptide specific antigen (TPS), in serum and amniotic fluid obtained from
      normal, healthy, nonpregnant and pregnant Japanese women (NHNJW and NHPJW). The
      cut-off value of the serum TPS level was set at 130 U/l, based on the mean +2
      standard deviations in the NHNJW. The serial measurement of serum TPS levels
      demonstrated the significant temporal elevation of TPS level near the time of
      ovulation (+/- 3 days) in the ovulatory women. In the NHPJW, the mean serum TPS
      level and the positivity rate (> 130 U/l) increased with the advance of
      gestation, reaching 183.7 U/l and 66.7%, respectively, in the third trimester.
      Maternal serum levels were much elevated just before (mean: 982.3 U/l) and after
      (mean: 824.6 U/l) delivery, and were reduced to about one-fourth by 3 days. In
      addition, markedly high TPS concentrations were found in the retroplacental blood
      (one case: 9,076 U/l) and the amniotic fluid (mean: 11,650 U/l). The serum TPS
      level correlated well (r = 0.871) with the serum TPA level in the TPS range of 2
      2,000 U/l, while a poor correlation (r = 0.273) was found in the TPS range of 2
      500 U/l. The present study thus obtained fundamental data on TPS in Japanese
      women. The fluctuation and change of serum TPS levels during the menstrual cycle
      and in pregnancy should be taken into consideration when we apply TPS as a tumor
      marker for women.

PMID- 8135681
TI  - Why study the history of psychiatry?
AB  - The history of psychiatry is being neglected. The major psychiatric textbooks no
      longer offer any overview of psychiatric history. Possible reasons for this
      indifference are discussed. It is suggested that a knowledge of our history is
      not only necessary in a general intellectual sense, but also specifically in
      enabling us to more easily tolerate the incompleteness and ambiguity of many of
      our concepts. Furthermore, it may help psychiatry to more convincingly explain
      the reality and consequences of mental illness to a sceptical public.

PMID- 8135682
TI  - The genetics of bipolar disorder.
AB  - Growing interest in the application of molecular biological techniques to
      psychiatric disorders has reinvigorated interest in the genetics of the
      psychoses. It is therefore timely to review the current state of knowledge of the
      genetics of bipolar disorder. Family, twin and adoption studies are all
      consistent in confirming the strongly heritable nature of this condition. As
      segregation analyses have been unable to determine the mode of transmission of
      bipolar disorder, ongoing linkage analyses using DNA markers will be crucial in
      determining whether this condition is due to a single major gene, a small number
      of genes, or multifactorial polygenic inheritance.

PMID- 8135683
TI  - A consensus conference on psychotic depression.
AB  - We report a consensus conference on psychotic depression that addressed historic,
      classification, phenomenologic, epidemiologic, aetiologic, management and outcome
      issues. We were able to detail the impact of the information offered by having
      audience members complete questionnaires before and after the conference. The
      respondents indicated that the status of psychotic depression (as a separate type
      or as a more severe expression of depression) remains unclear; that delusions,
      hallucinations and severe psychomotor disturbance have high cross-sectional
      diagnostic weighting (while longitudinal information is of importance); that
      determinants include both genetic and organic factors; that most patients with
      this condition require admission to hospital; and that bilateral ECT is the most
      effective treatment. The answers to the questionnaires established areas where
      the audience did not modify their responses because they were already well
      informed, others where their views were considerably changed (e.g. "psychotic"
      episodes in those with a borderline personality disorder) and others where they
      modified their clinical reasoning (e.g. "if a "psychotic" feature is mood
      congruent then the condition must be an affective disorder" became "if the
      patient has an affective disorder, the psychotic feature must be mood
      congruent"). Finally, we make some recommendations for future consensus
      conferences.

PMID- 8135684
TI  - Emotional lability after stroke.
AB  - The aims of this study were (i) to determine the frequency of emotional lability
      following first ever stroke, and (ii) to identify factors associated with this
      condition. Sixty-six consecutive inpatients with first ever stroke were surveyed
      two months post stroke for the presence of emotional lability. Demographic,
      clinical, psychiatric and stroke lesion characteristics were also assessed.
      Emotional lability was present in 12 of the 66 patients (prevalence: 18%).
      Emotional lability occurred independently of post stroke depression. Single
      lesions located in anterior regions of the cerebral hemispheres had four times
      the odds of emotional lability than lesions located anywhere else (p < 0.05).
      Emotional lability is a common emotional-behavioural syndrome following stroke
      and is probably a separate condition from post stroke depression. The aetiology
      of this condition is possibly related to the consequences of injury to anterior
      regions of the cerebral hemispheres.

PMID- 8135685
TI  - Risk of retraumatisation of asylum-seekers in Australia.
AB  - Australia has a long legacy of providing asylum to refugees who, it is now well
      established, suffer high rates of psychological and psychiatric problems
      requiring specialised treatment. In this paper we outline the special stressors
      faced by asylum-seekers who have not obtained formal refugee status and who are
      at risk of being forcibly repatriated. We suggest that the experiences they
      undergo in Australia, particularly that of prolonged detention, risk
      retraumatising an already vulnerable group. The implications for policy
      formulation are considered.

PMID- 8135686
TI  - Electroconvulsive therapy: a study of attitudes and attitude change after seeing
      an educational video.
AB  - Despite the proven efficacy of Electroconvulsive Therapy [ECT], negative
      attitudes occur in some patients towards its use. However, research into
      attitudes of patients and public towards ECT, and the influence of the media on
      these attitudes, is limited and often contradictory. The aims of this study were:
      to develop a self-administered questionnaire to assess attitudes; to assess the
      effect of an educational video on attitudes; and to assess the effect of the
      media on attitudes. The questionnaire was administered to psychiatric and non
      psychiatric patients of a Veterans' hospital and to a group of general hospital
      patients. A video was shown to a randomly assigned group of the Veteran hospital
      psychiatric patients. Their attitudes were assessed before and after the video.
      An overall positive attitude towards ECT was demonstrated in all three groups.
      Showing a video to the Veteran psychiatric patients produced an improvement in
      some attitudes, but no reduction in fear. For the psychiatric patients, the
      effect of the media was negative.

PMID- 8135687
TI  - The historical method in psychiatric research.
AB  - This paper describes the historical method of psychiatric research and compares
      it with the method of natural science. Examples are provided of methodological
      errors in the use of this method: errors in the gathering of clinical evidence
      and the drawing of inferences. The paper concludes that the historical method
      need be no less rigorous in its application than the method of natural science,
      and that both methods are necessary in the comprehensive formulation of a
      psychiatric case.

PMID- 8135688
TI  - Inequalities in the regional distribution of private psychiatric services
      provided under Medicare.
AB  - An analysis was carried out on Medicare data to find out if there are
      inequalities in the geographical distribution of private psychiatric services in
      Australia. The number of psychiatric services and persons becoming patients per
      100,000 population was calculated for each federal electorate for the year
      1985/86 and related to social indicators derived from the 1986 census. As a
      comparison, services provided by consultant physicians were analyzed as well. The
      data were based on the electorate of the patient rather than the electorate of
      the practitioner. Consultant psychiatrist services were found to be received more
      often in high socio-economic status electorates and those with older populations,
      and less often in rural areas. A similar pattern was found for consultant
      physician services, although the relationship with socio-economic status was not
      as strong. Frequent psychiatric consultations of longer duration, which are an
      indicator of insight psychotherapy, were more common in higher socioeconomic
      status electorates. A limitation of the Medicare data is that they cover only
      private services. To overcome this limitation, a supplementary analysis was
      carried out on the distribution of consultations for mental disorders using data
      from the National Health Survey. These data confirmed that individuals of high
      socio-economic status with a mental disorder are more likely to receive
      specialist treatment.

PMID- 8135689
TI  - Wernicke's encephalopathy complicating schizophrenia.
AB  - Wernicke's encephalopathy producing an altered mental state may occur in
      malnourished psychiatric patients even in the absence of alcohol abuse. A case is
      reported of a woman, aged 61 years, with schizophrenia who refused her medication
      for four months, had the delusion she was dying from a tumour, and withdrew to
      her bed with a neglect of her nutrition. She was committed to hospital in a mute
      unresponsive state and after taking some food and fluids for four days lapsed
      into coma. She responded within three hours to the administration of thiamine.
      Clinicians need to remain vigilant to the possibility that an altered mental
      state in malnourished patients may be due to thiamine deficiency rather than to
      the primary psychiatric disorder. If doubt exists as to the presence of
      Wernicke's encephalopathy, then parenteral thiamine should be administered.

PMID- 8135690
TI  - Adolescent suicide clusters: evidence, mechanisms and prevention.
AB  - Cluster suicides account for an estimated 5% of all teenage suicides in the USA.
      Not all hypothesised clusters are verified, however, when submitted to
      statistical analysis. This paper reviews possible mechanisms underlying
      adolescent cluster suicides using the "infectious disease model", key concepts of
      which are host susceptibility, modes of transmission, degree of virulence, and
      dose dependency. Preventive measures against cluster suicides are reviewed,
      including primary prevention against youth suicide, tempered media reporting of
      suicide, and "postvention strategies" directed to communities affected by
      suicide.

PMID- 8135691
TI  - Clinical and research implications of the co-occurrence of Asperger's and
      Tourette syndromes.
AB  - Recent advances in the understanding of Tourette Syndrome and Asperger's Syndrome
      are reviewed. Reports of the co-occurrence of these two uncommon
      neuropsychological disorders pose a number of questions, the answers to which are
      likely to have implications for other conditions at the interface of psychiatry
      and neurology.

PMID- 8135692
TI  - Conduct problems and attention deficit behaviour in middle childhood and cannabis
      use by age 15.
AB  - The relationship between conduct problems and attention deficit behaviours at
      ages 6, 8, 10 and 12 years and the early onset of cannabis usage by the age of 15
      years was studied in a birth cohort of New Zealand children. The analysis showed
      that while conduct problems during middle childhood were significantly associated
      with later cannabis use (p < 0.05) there was no association between early
      attention deficit behaviours and cannabis use (p > 0.40) when the associations
      between conduct problems and attention deficit behaviours were taken into
      account. It was estimated that children who showed tendencies to conduct disorder
      behaviour in middle childhood were between 2.1 to 2.7 times more likely to engage
      in early cannabis use than children not prone to conduct problems even when a
      range of factors including family social background, parental separation and
      parental conflict were taken into account. It is concluded that early conduct
      disorder behaviours are a risk factor for later cannabis use when due allowance
      is made for social and contextual factors associated with both early conduct
      problems and later cannabis use.

PMID- 8135693
TI  - Communications between medical referrers and child psychiatry staff.
AB  - Communicating in organisations is often seen as the key to good practice, good
      relationships and good service. A survey was conducted on what communication was
      wanted by medical referrers to a Department of Child and Family Psychiatry, the
      types of feedback preferred, and its timing and content. The main finding was
      that paediatricians received different and better information about referred
      patients than general practitioners.

PMID- 8135694
TI  - Non-sexist Sexual Experiences Survey and Scale of Attraction to Sexual
      Aggression.
AB  - Sixty-six male and 51 female second year medical students anonymously completed
      the Sexual Experiences Survey (SES) and the Attraction to Sexual Aggression (ASA)
      Scale, both modified so that women could report behaviours in which they were
      aggressors, and men, behaviours in which they were victims. Men's aggression
      scores on the two scales were significantly correlated. As expected, more men
      than women reported both the likelihood and the experience of being sexual
      aggressors, although 6% of women reported being so aroused they couldn't stop
      when their partner didn't want intercourse and 13% of men reported having
      intercourse against their will. In men sexually coercive behaviours correlated
      positively with the masculinity scale of the Bem Sex Role Inventory. Fewer female
      medical students reported experiencing sexually aggressive behaviours compared to
      US or New Zealand university students; however, the percentage of male students
      who reported using or threatening to use physical force was in the same range as
      that of US students. Significant attention to the issue of sexual coercion would
      appear necessary in the education of medical students.

PMID- 8135695
TI  - Conversion disorder revisited: severe parasomnia discovered.
AB  - In light of recently described and reviewed disorders of movement and behaviour
      during sleep, the long standing diagnosis of conversion disorder in a forty-nine
      year old Vietnam veteran was reappraised. Polysomnographic studies showed that
      the nocturnal component of his "pseudoseizures" was due to physical disorder, a
      severe mixed parasomnia comprising the recently described REM behaviour disorder
      and a non-REM parasomnia. His sleep architecture was also deranged, featuring
      reduced REM latency and increased REM density. An association between these
      abnormalities and psychological trauma is recognised in the literature. Treatment
      with clonazepam has abolished the nocturnal behavioural disturbance. His daytime
      pseudoseizures occur less frequently and his general well being is improved. The
      case is a reminder that physical disorder may underlie and act as prototype to
      the psychologically-driven symptom. Before attributing behavioural disturbance at
      night to psychological causes alone, polysomnographic studies should be done to
      exclude a treatable parasomnia.

PMID- 8135696
TI  - Generalised dissociative amnesia.
AB  - A case of generalised dissociative amnesia is presented, which illustrates
      several characteristic features of this uncommon condition. The case showed poor
      response to thiopentone interviews and in vivo cueing. Amnesia had persisted at
      six months follow up.

PMID- 8135697
TI  - Multiple personality disorder and satanic ritual abuse.

PMID- 8135698
TI  - Male patients with anorexia nervosa.

PMID- 8135699
TI  - Chlorpromazine turns forty.

PMID- 8135700
TI  - Evolution of the gastrointestinal endocrine system (with special reference to
      gastrin and CCK).
AB  - The evolution of gut endocrine cells can be seen to have depended in the first
      instance on the expression of genes encoding regulatory peptides in cells that
      had evolved the regulated pathway of secretion. It seems probable that the
      endocrine cells made use of molecules and mechanisms that first emerged in early
      nervous systems. However, by the start of the vertebrate line of evolution, most
      of the major families of gut hormones were already found in association with
      endocrine cells. A single common class of receptor with seven transmembrane
      domains and acting via association with G-proteins transduces many (perhaps all)
      gut peptide actions. The duplication and divergence of receptors and peptides can
      now be traced, in outline at least, for gastrin and CCK in vertebrates. Even in
      phylogenetically similar groups such as birds and mammals, quite different
      molecular approaches have been applied to solving the same physiological problem.
      Evolution of the modern gastrointestinal control system evidently depended in
      this case both on molecular evolution of peptides and receptors and on cells
      expressing the genes encoding them.

PMID- 8135701
TI  - Gut hormones and intestinal function.

PMID- 8135702
TI  - Humoral regulation of intestinal adaptation.
AB  - After the loss of small bowel through disease or surgery the residual bowel
      adapts by increasing its functional capacity. This process of adaptation involves
      dilatation, hypertrophy and mucosal hyperplasia, particularly distal to the area
      of bowel loss or disease. The response of the residual bowel is mediated by a
      complex interplay of factors including luminal nutrition, pancreaticobiliary
      secretions, luminal or local growth factors and also humoral or endocrine
      factors. The experimental model commonly used to characterize the adaptive
      response, massive small bowel resection (MSBR), involves 80% resection of the
      small bowel in the rat. Of the various putative humoral factors, most work has
      focused on the products of the ileal L cells: enteroglucagon and peptide YY.
      Plasma levels of both hormones are increased after MSBR and indeed their mRNA
      levels are also increased as a result of an increase in the amount of message per
      L cell. Whilst PYY probably serves as an 'ileal brake' to slow the movement of
      the luminal contents and hence increase their mucosal contact time, the role of
      the enteroglucagon is unresolved. The molecular cloning of the proglucagon gene
      has revealed, firstly, that there are a number of biologically active peptides
      which derive from the propeptide and, secondly, that tissue-specific differential
      processing occurs. Most studies do not clearly define which of these products of
      proglucagon is being measured and is termed as glucagon-like or enteroglucagon
      immunoreactivity. The insulin-like growth factors (IGF) have a potent mitogenic
      action on the bowel. Their role after MSBR is likely to be largely paracrine.
      Though IGF-I mRNA levels do not increase after MSBR, the precipitous and early
      fall in ileal IGF-binding protein-3 (IGFBP-3) mRNA levels suggests a fall in
      IGFBP-3 levels may increase local IGF-I bioactivity. Polyamine synthesis is a
      critical component of the adaptive response, although the stimulus to their
      dramatic increase in synthesis after MSBR remains to be elucidated. Other humoral
      factors such as cholecystokinin, neurotensin and bombesin probably have minor
      indirect roles in the adaptive response. Components of the epidermal growth
      factor/transforming growth factor alpha response pathway family of growth factors
      may be involved as paracrine regulators. There is thus strong evidence that
      humoral factors play an important role in intestinal adaptation; characterization
      of the nature of the humoral factors and their relationship with other influences
      such as luminal nutrition and pancreatic biliary secretions may facilitate the
      development of new therapeutic strategies for the short bowel syndromes.

PMID- 8135703
TI  - Measurement of gut hormone gene expression: mRNA and peptides.
AB  - During the past decade numerous methods for measurement of mRNA and peptides have
      been developed. Since the expression cascade from DNA to protein is regulated at
      all levels, the methods should be carefully designed to accomplish the purpose of
      the analysis. Regulation of the nuclear processing, the translational activity
      and the decay of a particular mRNA changes the proportionality between
      transcriptional activity and production of prepropeptide. Moreover, the post
      translational maturation of the pro-hormones may be attenuated. Detection of mRNA
      is valuable and feasible because it is easy to generate cDNA probes for most
      hormones, and because mRNA demonstration unequivocally indicates the cellular
      site of gene expression. The deduction of preprohormone structures has also made
      it possible to improve the versatility of radioimmunoassays (RIA). Monospecific
      antibodies and pure tracers have allowed the development of sequence-specific RIA
      libraries for bioactive peptides and their precursors. Recently we have
      introduced a simple processing-independent analysis (PIA) for clinical use, since
      the post-translational maturation of gut peptides may be changed in
      gastrointestinal diseases. So far PIA has improved the diagnostic sensitivity for
      gut hormone tumours.

PMID- 8135704
TI  - Thought suppression induces intrusion in naturally occurring negative intrusive
      thoughts.
AB  - It has been hypothesized that personally relevant negative intrusive thoughts may
      be the direct precursors of obsessional thinking. Efforts made to suppress or
      neutralize are said to be involved in the transition between 'normal' and
      'abnormal' intrusive thoughts. In order to test this hypothesis, naturally
      occurring intrusive thoughts were identified in non-clinical subjects, some of
      whom were asked to suppress these thoughts during an experimental period. The
      occurrence and characteristics of the target intrusive thoughts during
      suppression and a subsequent non-suppression period were assessed. The results
      indicate that (i) suppression can result in increased intrusion; and (ii) that
      distraction can play an important moderating role. It is suggested that, in
      suppression experiments, the effects of self-monitoring per se may have been
      underestimated. Motivated and intrusion-focussed monitoring of consciousness may
      be as important as suppression, given that obsessional patients tend to be
      constantly vigilant for the occurrence of obsessional thinking.

PMID- 8135705
TI  - Does parent training with young noncompliant children have long-term effects?
AB  - The current study was a long-term follow-up (approx. 14 yr following treatment)
      of 26 late adolescents/young adults (17 yr and older) who had participated in
      parent training with their mothers when they were young (2-7 yr old) noncompliant
      children. Parent training, consisting of teaching mothers to use attends and
      rewards for appropriate behavior, clear commands and time-out, had reduced
      deviant behavior and increased compliance immediately following treatment. At
      this follow-up, these individuals were compared to a matched community sample on
      various measures of delinquency, emotional adjustment, academic progress and
      relationship with parents. No differences emerged between the two groups on any
      of the measures, suggesting that noncompliant children who participated in parent
      training during their early years are functioning as well as nonclinic
      individuals as they move into adulthood.

PMID- 8135706
TI  - Dyspneic-fear theory explains hyperventilatory panic attacks: a reply to Carr,
      Lehrer and Hochron.
AB  - Carr, Lehrer and Hochron (Behaviour Research and Therapy, 30, 251-261, 1992)
      attempted to test Ley's (Behaviour Research and Therapy, 30, 549-554, 1989)
      dyspneic-fear theory and concluded that while their results confirmed predictions
      for a sample of asthmatics, their results did not confirm predictions for a
      sample of panic-disorder patients. The present paper points to a basic flaw in
      the Carr et al. study which renders their conclusions regarding panic disorder
      indeterminate. The flaw in the Carr et al. study lies in their selection of panic
      disorder patients. Whereas dyspneic-fear theory provides an explanation for panic
      fear experienced in hyperventilatory panic attacks, Carr et al. overlooked this
      fact and selected Ss based on the DSM-IIIR classification, a set of criteria
      which does not distinguish between hyperventilatory panic attacks and other types
      of panic attacks (see Ley, Behaviour Research and Therapy, 30, 347-357, 1992).

PMID- 8135707
TI  - Reply to Ley's "dyspneic-fear theory explains hyperventilatory panic attacks".
AB  - In a critique of the study by Carr, Lehrer and Hochron (1992), Ley (Behaviour
      Research and Therapy, 32, 109-111, 1994) attributes the lack of confirmation for
      his dyspneic-fear theory among panic disorder patients to a basic flaw of that
      study: Ss were selected according to DSM-IIIR criteria. Ley argues that dyspneic
      fear theory pertains exclusively to hyperventilatory (characterized by intense
      dyspnea) panic attacks not to all attacks that come under the classification of
      DSM-IIIR. We address the premise concerning the selection of Ss and argue that
      cognitive theory continues to offer a more convincing explanation of our study
      and of more recent findings by others.

PMID- 8135708
TI  - The Herald of Free Enterprise disaster: the relationship of intrusion and
      avoidance to subsequent depression and anxiety.
AB  - Twenty-five survivors completed the Impact of Events Scale, a measure of
      intrusive reexperiencing and avoidant behaviour, approx. 7 months following the
      Herald of Free Enterprise disaster. The aim of the present study was to examine
      the relationship of scores on these scales to scores on the Beck Depression
      Inventory and the Spielberger State Anxiety Inventory at approx. 19 months
      subsequent to the event. Greater intrusive reexperiencing was found to be
      associated with greater depression and anxiety over and above the intensity of
      exposure and the fact of bereavement. These data are discussed with reference to
      a cognitive processing model of post-traumatic stress.

PMID- 8135709
TI  - Cognitive processing of idiographic emotional information in panic disorder.
AB  - Panic disorder patients, obsessive-compulsive disorder (OCD) patients, and normal
      control subjects performed a computerized Stroop color-naming task in which they
      named the colors of panic-threat words (e.g. Collapse), general-threat words
      (e.g. Infectious), positive words related to panic (e.g. Relaxed), and neutral
      words (e.g. Sleepy). Idiographic stimulus selection ensured their personal
      emotional relevance for each subject. In accordance with prediction, panic
      patients, but not OCD patients, exhibited greater interference for panic-threat
      words than for positive words related to panic and for neutral words. Panic
      patients did not respond differentially to panic-threat and general-threat words.
      Complexities concerning attentional bias research in the anxiety disorders are
      discussed.

PMID- 8135710
TI  - Pupillometric discrimination of insomniacs.
AB  - Unlike the multiple sleep latency test, pupillometry does not require sleep to
      test sleepiness, which may be an advantage in assessing insomniacs. Pupillometry
      was employed to study possible differences in daytime sleepiness between
      insomniacs and noninsomniacs. Thirty self-defined insomniacs and an equal number
      of noninsomniacs, age 30-50 yr, submitted to four 10-min pupillometry sessions
      distributed from early morning to bedtime. The sessions consisted of infrared
      television monitoring of the pupil in a totally dark, nonstimulating environment.
      Insomniacs exhibited significantly smaller pupil diameters than noninsomniacs,
      and this effect persisted in all sessions. However, the size of effect averaged
      about 0.5 mm, and this was judged to be a small magnitude. Heightened subjective
      sleepiness discriminated the insomniacs in only the midday session. The absence
      of polysomnography was a methodologically limiting factor. Theoretical and
      clinical implications of these data were discussed.

PMID- 8135711
TI  - Cross-cultural validity of a parent's version of the Dental Fear Survey Schedule
      for children in Chinese.
AB  - The cross-cultural validity of a parent's version of the Dental Fear Survey
      Schedule (DFSS) for children was assessed by examining the relationship between
      the parent's report of child fear in Chinese (DFSS) and actual child behavior
      (CB) in the dental environment for two samples: 70 Chinese children ages 5-15 yr,
      residing in Canada, and 99 mainland Chinese children ages 2.5-7.0 yr residing in
      Kunming, Yunnan, PRC Canadian DFSS score M = 31.9 (SD = 9.5) with no differences
      by age or sex. PRC DFSS score M = 35.7 (SD = 8.9) with girls reported more
      fearful than boys. No age difference was detected. Higher DFSS scores were
      associated with more CB in both samples. Factor analyses yielded similar
      solutions and internal consistency was high. Control and potential victimization
      were identified as important constructs. The results suggest the Chinese version
      of the DFSS is a reliable and valid parental measure of child dental fear.

PMID- 8135712
TI  - Mood and personality in recall of positive and negative information.
AB  - The present study examined the relationships between a number of personality and
      mood indices, and memory bias. Results suggested that Neuroticism scores were
      associated with negative recall but this effect depended on current level of
      dysphoria. Across the sample as a whole, negative recall bias appeared to be
      associated with general negative affect. When the sample was divided into high
      and low dysphoric groups, Neuroticism predicted increased negative recall only in
      the high dysphoria group. These results suggest that the tendency to recall
      negative information may be an interactive function of depressed mood and
      vulnerable personality.

PMID- 8135713
TI  - Obsessions, responsibility and guilt: two case reports suggesting a common and
      specific aetiology.
AB  - Inflated responsibility, guilt and the psychological fusion of thought and action
      feature prominently in contemporary accounts of obsessional phenomena. Two cases
      are reported in which the presence of these features can be explained by a
      specific formative learning experience. Some implications for therapy are
      considered.

PMID- 8135714
TI  - Cognitive assessment of unipolar depression: measuring products, processes and
      structures.
AB  - In this article we survey current and emerging approaches to the cognitive
      assessment of affective disorder. Our review begins with an evaluation of the
      role of cognition in prevailing multidimensional models of unipolar depression.
      Within this framework, we distinguish three classes of cognitive variables that
      are operative in depression, and review strategies for assessing them. First, we
      consider methods of measuring cognitive product variables in depression (e.g.
      automatic thoughts, attributions, negative self-evaluations). Next, we focus on
      the assessment of cognitive and social cognitive mechanisms (e.g. irrational
      thought processes, social comparison processes) thought to play a proximal role
      in the development and maintenance of depressive phenomenology. Third, we review
      strategies for measuring the content and organization of the knowledge structures
      (i.e. schemas) postulated to underlie both products and processes. We conclude
      with a discussion of general issues and future directions for research.

PMID- 8135715
TI  - Development of a coding system for marital problem solving efficacy.
AB  - Efficacy in marital problem solving has received little attention, and work on
      general problem solving efficacy does not address marital issues. This study
      examined the ability to discriminate between groups and criterion validity of an
      efficacy-focused marital problem solving measurement method, the Marital Efficacy
      Coding System, which combines marital problem scenarios with general social
      problem solving assessment procedures. This system was administered to
      nondistressed married subjects, participants in marital therapy, and divorced or
      separated individuals. Participants were asked to develop a set of discrete steps
      or 'means' as solutions to marital problem scenarios. The content was coded by a
      number of means, participants' ratings of problem frequency and typicality of
      response, and coders' ratings of efficacy and equality. Overall percentage
      agreement between coders was 73.4%. Marital Efficacy Coding System variables,
      including problem frequency, solution typicality, and solution efficacy, were
      shown to significantly differentiate between participants high and low in marital
      satisfaction and to possess significant predictive ability.

PMID- 8135716
TI  - Assessment of the effects of urges and negative affect on smokers' coping skills.
AB  - A taped-situation test designed to elicit descriptions of how subjects would cope
      with circumstances that placed them at high risk for relapse to smoking was
      administered to 60 cigarette smokers following their participation in one of
      three treatment groups. Two of these groups had coping-response training
      incorporated into the treatment format. The negative affect and urge contents of
      eight scenarios were manipulated to examine the effect of these variables on
      coping responses. The predictive validity of this assessment was evaluated by
      conducting follow-up interviews for up to 1 yr following the assessment. The
      manipulation of negative affect and urges had an impact on cognitive and
      behavioral coping. The type of treatment the subjects received had no effect on
      any of the coping-response measures. Among the 49 subjects abstinent at the time
      of the coping assessment, measures of coping (especially those obtained when
      urges and negative affect were increased) and self-efficacy ratings were
      predictive of days to first relapse. The implications of the results for the
      assessment of coping-responses and conceptualizations of the role of coping in
      the relapse process are discussed.

PMID- 8135717
TI  - Precipitating events, locations and reactions associated with initial unexpected
      panic attacks.
AB  - This study examined the phenomenology of the initial panic attack in 85 panic
      disorder patients with or without agoraphobia. Patients were divided into minimal
      and extensive avoiders and three domains were assessed: precipitating factors,
      location of initial panic, and reaction to the panic. No apparent precipitating
      factor could be identified in approx 40% of the patients. The most common
      precipitants were injury/illness and interpersonal conflict. Extensive avoiders
      were more likely to have experienced the initial panic in classic agoraphobic
      situations. Public transportation was the most common location for the total
      sample. In reaction to the panic, minimal avoiders were more likely to have gone
      to a hospital emergency room (ER) whereas extensive avoiders were more likely to
      have done nothing in terms of help-seeking. Many patients with either minimal or
      extensive avoidance avoided the locations where the initial panic occurred,
      suggesting that circumscribed avoidance does not always generalize.

PMID- 8135718
TI  - Social desirability and self-reports of alcohol abuse in anxiety disorder
      patients.
AB  - Previous research has shown there is significant comorbidity between alcohol
      abuse and anxiety disorders. However, the prevalence of anxiety disorders in
      alcoholic samples has been found to be higher than the occurrence of alcohol
      abuse in anxiety disorder samples. One possibility for this apparent discrepancy
      involves a social desirability response bias where it may be less socially
      acceptable to report alcoholism than to report an anxiety disorder. Thus, a high
      need for social approval may be associated with minimizing alcohol abuse. The
      relationship between standardized self-reports of alcohol abuse and social
      desirability was assessed in 51 panic disorder (PD) and 33 social phobia (SP)
      patients. In male PD patients there was a negative correlation (-0.46) between
      social desirability and self-reports of alcohol abuse that approached statistical
      significance, and the prevalence of alcohol abuse was 18%. In male SP patients
      there was no such inverse relation and the prevalence of alcohol abuse was much
      higher (47%). In female anxiety disorder patients these patterns were not
      evident. These results suggest that when there is a strong (negative)
      relationship between self-reports of alcoholism and social desirability, the
      alcohol use may be minimized. In general, however, this relationship was not
      pronounced in most anxiety disorder patients.

PMID- 8135719
TI  - Men are innocent until proven guilty: a comment on the examination of sex
      differences by Pierce and Kirkpatrick (1992).
AB  - Pierce and Kirkpatrick (1992, Behaviour Research and Therapy, 30, 415-418)
      addressed the finding that men reported lower levels of fear than women in
      response to specific fear items and concluded on the basis of their experiment
      that this was because the men were lying. Their conclusion is questioned on
      various grounds, including inappropriate statistical analyses, inadequate
      treatment of physiological data, failure to address the possibility of sample
      selection bias (signalled by the high drop-out rate) and the inadequacy of self
      assessed fear measures based on a small number of single items. An alternative
      interpretation of their data is offered, based on the inverse correlation between
      initial response level and size of increment, demonstrable in their study in
      males but not in females. It is argued here that the increments may have been due
      to anticipatory arousal, a mediating factor that would also account for the
      facilitation of generalization between certain specific items. It is further
      suggested that, if this explanation is correct, the men were acting with more
      rather than less honesty, and it may on the other hand be the reports of the
      females that were affected by their sex-role stereotype. Another possible
      explanation of the findings is discussed. If men relatively high in masculinity
      had a greater tendency to drop out, the experimental sample at the second testing
      would be biased towards men relatively low in masculinity and reporting higher
      fear levels.

PMID- 8135720
TI  - Self-report of obsessions and worry.
AB  - The relationships between self-reported worry and obsessional-compulsive symptoms
      were examined among 145 hospital outpatients. Subjects completed the Penn State
      Worry Questionnaire and the Padua Inventory. Despite moderately strong
      correlations, the scales measured distinct constructs. Eliminating five items
      from the Padua Inventory may improve its discriminant validity. Correlations with
      the Padua Inventory subscales showed that obsessional loss of mental control was
      moderately correlated to both worry and checking, whereas worry and checking were
      only weakly correlated. The results are discussed in terms of possible
      relationships between worry and obsessions.

PMID- 8135721
TI  - Comparison of cognitive-behavior therapy and desipramine in the treatment of
      bulimia nervosa.
AB  - A comparison of cognitive-behavior therapy alone, desipramine alone, and
      cognitive-behavior therapy combined with desipramine was made in the treatment of
      bulimia nervosa. The study was terminated early with an N of only 7 subjects per
      condition because of a high drop-out rate and lack of positive response in the
      desipramine alone group compared to the other two groups. By this time it was
      also apparent that at posttreatment and at 6 months follow-up no benefit was
      being realized from combining cognitive-behavior therapy with desipramine.

PMID- 8135722
TI  - Personality traits in subclinical and non-obsessive-compulsive volunteers and
      their parents.
AB  - Theorists from a variety of perspectives have asserted that obsessive compulsives
      are more risk-aversive, perfectionistic and guilt-ridden than non-obsessive
      compulsives, and that these characteristics are central features of the disorder.
      Furthermore, several have hypothesized that the parents of obsessive compulsives
      are characterized by risk-aversion, perfectionism, and high levels of criticism.
      Little research exists which corroborates these hypotheses, however. The present
      investigation examined these hypotheses among subclinical obsessive compulsives.
      In two different samples, subclinical obsessive compulsives were found to be more
      risk-aversive, perfectionistic, and guilt-ridden. Subclinical obsessive
      compulsives also perceived their parents to be more overprotective. The findings
      regarding other parental traits were less clear. There was some support for the
      hypothesis that the parents of subclinical obsessive compulsives are more risk
      aversive, and that fathers are more critical and perfectionistic.

PMID- 8135723
TI  - Disease-avoidance model: factor analysis of common animal fears.
AB  - This paper reports the results of two studies investigating a disease-avoidance
      model of common animal fears. In Study 1, a factor analysis of a variety of self
      rated animal fears revealed that these fears can be grouped into two
      theoretically meaningful categories which correspond to predatory animals and
      fear-relevant animals. Study 2 found a significant correlation between disgust
      sensitivity and fear to animals in the fear-relevant category, but not between
      disgust sensitivity and fear to animals in the predatory category. In addition,
      fear of animals in the fear-relevant category was significantly associated with
      scores on the obsessive washing sub-scale of the Maudsley Obsessive-Compulsive
      Inventory, but was not associated with obsessive behaviour in general.

PMID- 8135724
TI  - Implicit and explicit memory for emotional information in non-clinical subjects.
AB  - The study investigated implicit and explicit memory for emotional words in 53 non
      clinical Ss. The implicit memory test was a primed lexical decision task, which
      included anxiety- and depression-relevant words, and supraliminal and subliminal
      priming conditions. The explicit memory test was incidental free recall following
      a self-referent encoding task. Subjects were divided into high and low negative
      affect groups, differing in trait and state anxiety, and depression scores. The
      high negative affect group showed greater subliminal priming of depression
      relevant than neutral control words compared with the low negative affect group.
      This selective priming effect was more closely associated with depression than
      anxiety measures. There was little direct evidence of emotion-congruent biases on
      the supraliminally primed lexical decision and free recall tasks, although when
      the effects of anxiety were partialled out depression scores predicted relatively
      better recall of depression-relevant words. In conclusion, the main results that
      non-clinical depression is associated with a mood-congruent bias in automatic
      aspects of implicit memory.

PMID- 8135725
TI  - Cognitive therapy for obsessive-compulsive disorder.
AB  - This paper discusses three cognitive models for the obsessive-compulsive disorder
      (OCD). Further, a cognitive formulation of OCD while stresses the importance of
      the perception of danger and responsibility is described. Several specific
      cognitive interventions, which address the estimation of catastrophes and the
      perception of personal responsibility, are presented and illustrated with patient
      material. Furthermore, problems with cognitive therapy with OCD patients are
      described and some solutions for these pitfalls are discussed. Finally, the
      findings of controlled studies into cognitive therapy with OCD are given.

PMID- 8135726
TI  - Memory bias in social phobia.
AB  - To examine memory bias for social threat in social phobics, four studies are
      reported in which social phobic and nonclinical Ss are compared on their
      retrieval of threat-relevant information. Study 1 measured standard recall and
      recognition of threat, neutral, and positive words, while Study 2 assessed
      retrieval of these words through implicit and explicit tasks. The two final
      studies attempted to increase the validity of the procedures. Study 3 examined
      recall of feedback in a hypothetical public performance task and Study 4 examined
      autobiographical memory for social and neutral situations. All four studies
      consistently failed to find any evidence for biased retrieval processes in social
      phobics.

PMID- 8135727
TI  - Detecting depression in chronic pain patients: adequacy of self-reports.
AB  - Depression, a complex psychobiological syndrome, has been found to be prevalent
      among individuals with chronic pain problems. It has been repeatedly recommended
      that chronic pain patients be routinely screened for depression. Many self-report
      questionnaires have been used to screen for depression although few have
      addressed potential limitations of using a self-report questionnaire to identify
      depressed chronic pain patients. Among the most serious problems is an over
      diagnosis since typical neurovegetative symptoms of depression often resemble
      patients' medical/physical conditions. Some have suggested that the physical
      items should be replaced and others have suggested that a higher cut-off criteria
      for diagnosing depression should be used. In this study, the validity of the
      Center for Epidemiological Studies-Depression (CES-D) scale was examined to
      determine (a) its sensitivity, specificity, and positive, and negative predictive
      value with chronic pain patients, (b) the biasing effect of somatic items, and
      (c) the optimal cut-off score for diagnosing depression. The results support the
      predictive validity of the CES-D and suggest that a cut-off score of 19 should be
      used for diagnosing depression in chronic pain patients rather than the standard
      cut-off point of 16. Interestingly, the removal of the somatic items did not
      enhance the effectiveness of the CES-D. The discriminatory ability of somatic
      items with the total assessment of depression is discussed.

PMID- 8135728
TI  - Affinity of okadaic acid to type-1 and type-2A protein phosphatases is markedly
      reduced by oxidation of its 27-hydroxyl group.
AB  - Okadaic acid (OA), a potent inhibitor of type-1 and type-2A protein phosphatases
      (PP1 and PP2A), has four hydroxyl groups at 2, 7, 24 and 27 positions (see Figure
      1). By chemical treatment of OA we synthesized a derivative, in which the 27
      hydroxyl group was specifically oxidized (27-dehydro-OA). The inhibitory effect
      of this OA derivative was examined on the activities of PP1 and PP2A, which were
      inhibited by intact OA with dissociation constants (Ki) of 150 nM and 32 pM
      respectively. We found that the affinity of OA was decreased 40-fold (Ki = 6
      microM) with PP1 and 230-fold (Ki = 7.3 nM) with PP2A after oxidation of the 27
      hydroxyl group. According to the model of the three-dimensional conformation of
      OA on the basis of X-ray analyses, the 27-hydroxyl group appears to be present in
      a position relatively free from intramolecular bonding formation, in comparison
      with the other three hydroxyl groups. The marked increases in the Ki values for
      PP1 and PP2A, which indicate the reduction of the absolute values of the free
      energy of binding by 9 kJ/mol and 14 kJ/mol respectively, may imply that the 27
      hydroxyl group serves as a binding site with the phosphatase molecules.

PMID- 8135729
TI  - Cloning and expression of a prostaglandin E receptor EP3 subtype from human
      erythroleukaemia cells.
AB  - Prostaglandins inhibit platelet activation by stimulating intracellular cyclic
      AMP formation. We have postulated that intracellular cyclic AMP levels in
      platelets are buffered by a distinct prostaglandin receptor that mediates
      inhibition of cyclic AMP formation. In order to provide evidence for the model,
      we have cloned the cDNA coding for a prostaglandin receptor EP3 subtype, which is
      coupled to inhibition of adenylate cyclase, from the megakaryocytic cell line
      human erythroleukaemia (HEL) cells. A PCR-generated hybridization probe, produced
      using primers based on the sequence of the mouse prostaglandin EP3 receptor
      published by Sugimoto, Namba, Honda, Hayashi, Negishi, Ichikawa and Narumiya
      [(1992) J. Biol. Chem. 267, 6463-6466], was used to screen a lambda gt11 HEL cell
      cDNA library. The composite full-length cDNA clone HEP3, generated from the two
      partial clones pHEP3-7 and pHEP3-5, is 1.6 kb long with an open reading frame
      coding for 390 amino acids. This clone is 83% identical to the alpha subtype of
      the mouse EP3 receptor. The full-length construct was transfected into COS-1
      cells. The cloned receptor exhibited the properties of a prostaglandin EP3
      subtype, inhibiting forskolin-stimulated cyclic AMP formation in response to
      prostaglandin E2 (PGE2) and binding PGE2 with high specificity and a Kd of 3.2
      nM. Radiolabelled PGE2 could be displaced by prostaglandins in the order PGE2 =
      PGE1 > iloprost = PGD2. Northern blot analysis revealed that the receptor is also
      present in human kidney.

PMID- 8135730
TI  - Rapid turnover of phosphatidylinositol 3-phosphate in the green alga
      Chlamydomonas eugametos: signs of a phosphatidylinositide 3-kinase signalling
      pathway in lower plants?
AB  - When Chlamydomonas eugametos gametes were incubated in carrier-free [32P]P1, the
      label was rapidly incorporated into PtdInsP and PtdInsP2 and, after reaching a
      maximum within minutes, was chased out by recirculating unlabelled P1 in the
      cell. This pulse-chase labelling pattern reflects their rapid turnover. In
      contrast, 32P incorporation into the structural lipids was slow and continued for
      hours. Of the radioactivity in the PtdInsP spot, 15% was in PtdIns3P and the rest
      in PtdIns4P, and of that in the PtdInsP2 spot, 1% was in PtdIns(3,4)P2 and the
      rest in PtdIns(4,5)P2, confirming the findings by Irvine, Letcher, Stephens and
      Musgrave [(1992) Biochem. J. 281, 269-266]. When cells were labelled with carrier
      free [32P]P1, both PtdInsP isomers incorporated label in a pulse-chase-type
      pattern, demonstrating for the first time in a plant or animal system that D-3
      poly-phosphoinositides turn over rapidly in non-stimulated cells, with kinetics
      similar to those shown by the D-4 isomers. In animal systems such lipids are
      already established as signalling molecules, and the data suggest that a similar
      role must be sought for them in lower plants such as Chlamydomonas.

PMID- 8135731
TI  - Autoinduction of activin genes in early Xenopus embryos.
AB  - Activin exhibits a potent mesoderm inducing activity towards the ectodermal
      tissue (animal cap) of Xenopus laevis blastulae. Thus in order to investigate the
      role of activin in morphogenesis of early Xenopus embryos, activation of genes
      for activin beta A and beta B was examined by the reverse transcription
      polymerase chain reaction. In vivo, activin beta B mRNA appears to be present in
      embryonic stage 1 whereas beta A mRNA is undetectable prior to gastrulation. beta
      B and beta A mRNAs were noted to accumulate after stages 9 and 15 respectively.
      Activin gene expression in Xenopus animal caps was examined after treatment with
      various concentrations of activin A. Under these treatment conditions, both
      activin beta A and beta B mRNAs accumulated in a dose-dependent fashion after 24
      h. The same effect was noted for treatment with similar concentrations of activin
      B. Accumulation of mRNAs was inhibited by the addition of cycloheximide to the
      culture medium, consistent with the proposition that activin gene expression
      requires certain protein factors. In total, therefore, these data suggest that an
      autoinduction mechanism is involved in the regulation of activin mRNA levels in
      normal Xenopus embryos and that this mechanism may play a pivotal role during
      early embryonic development.

PMID- 8135732
TI  - Mechanism of inhibition of horseradish peroxidase-catalysed iodide oxidation by
      EDTA.
AB  - EDTA inhibits horseradish peroxidase (HRP)-catalysed iodide oxidation in a
      concentration and pH-dependent manner. It is more effective at pH 6 than at lower
      pH values. A plot of log Kiapp. values as a function of pH yields a sigmoidal
      curve from which a pKa value of 5.4 can be calculated for an ionizable group on
      the catalytically active HRP for EDTA inhibition. Among the structural analogues
      of EDTA, tetramethylethylenediamine (TEMED) is 80% as effective as EDTA, whereas
      the EDTA-Zn2+ chelate and EGTA are ineffective. Kinetic studies indicate that
      EDTA competitively inhibits iodide oxidation. Spectral studies show that EDTA can
      quickly reduce compound I to compound II, but reduction of preformed compound II
      to the native enzyme is relatively slow, as demonstrated by the time-dependent
      spectral shift from 417 nm to 402 nm through an isosbestic point at 408 nm. Under
      steady-state conditions, in a reaction mixture containing HRP, EDTA and H2O2, the
      enzyme remains in the compound-II form, with absorption maxima at 417, 527 and
      556 nm. Direct evidence for one-electron oxidation of EDTA by HRP intermediates
      is provided by the appearance of an e.s.r. signal of a 5,5-dimethyl-1-pyrroline N
      oxide (spin trap)-EDTA radical adduct [aN (hyperfine splitting constant) = 1.5
      mT] in e.s.r. studies. The signal intensity, however, decreases in the presence
      of iodide. The KD of the HRP-EDTA complex obtained from optical difference
      spectroscopy increases with an increase in iodide concentration, and the double
      reciprocal plot for EDTA binding indicates that EDTA and iodide compete for the
      same binding site for oxidation. We suggest that EDTA inhibits iodide oxidation
      by acting as an electron donor.

PMID- 8135733
TI  - Identification, partial purification and inhibition by guanine analogues of a
      novel enzymic activity which phosphorylates guanosine to GMP in the protozoan
      parasite Eimeria tenella.
AB  - From oocysts of the protozoan parasite Eimeria tenella, responsible for avian
      coccidiosis, we have partially purified and characterized a novel enzymic
      activity which specifically phosphorylates guanosine to GMP. The enzyme is able
      to use several phosphate donors, in the order: acetyl phosphate (Ac-P) > ATP >
      UTP > CTP > phosphoribosyl pyrophosphate (PRPP) > dUTP > or = dATP. The low
      specificity of this enzyme for the phosphate donor suggested that it be named
      guanosine phosphotransferase (GPTase). This enzyme is biochemically distinct from
      the previously described adenosine kinase (AK) and hypoxanthine/xanthine/guanine
      phosphoribosyltransferase (HXGPRTase), and may enable the parasite to synthesize
      guanine nucleotides under conditions of imbalance between adenine and guanine
      nucleotides. Because of its possible role in the purine salvage pathways, we have
      studied the effect of several guanine and guanosine analogues, recently
      synthesized in our laboratory, on the activity of GPTase in vitro. GPTase is
      specifically inhibited in the micromolar range by several substituted N2
      phenylguanine bases. These results indicate that, as previously found for AK and
      HXGPRTase, GPTase could be a potential target for antiparasitic chemotherapy.

PMID- 8135734
TI  - Probing the function(s) of active-site arginine residue in Leishmania donovani
      adenosine kinase.
AB  - The presence of arginine at the active site of Leishmania donovani adenosine
      kinase was studied by chemical modification, followed by the characterization of
      the modified enzyme. The arginine-specific reagents phenylglyoxal (PGO), butane
      2,3-dione and cyclohexane-1,2-dione all irreversibly inactivated the enzyme. In
      contrast, adenosine kinase from hamster liver was insensitive to these reagents.
      The inactivation of the enzyme by PGO followed pseudo-first-order kinetics, with
      a second-order rate constant of 39.2 min-1.M-1. Correlation between the
      stoichiometry of PGO modification and extent of inactivation indicated that
      modification of a single residue per molecule suffices for the loss of activity.
      Reactivity of the essential arginine residue towards PGO was affected by the
      presence of adenosine (Ado) and other competing alternative substrates,
      consistent with an arginine residue located proximal to the Ado-binding site. The
      enzyme showed an intrinsic fluorescence with an emission maximum at 340 nm when
      excited at 295 nm. The protein fluorescence was partially quenched on addition of
      Ado. PGO modification also led to significant quenching of the fluorescence.
      However, the fluorescence of the Ado-protected enzyme, which displayed 82% of the
      original activity after PGO treatment, was retained. The kinetic analyses of the
      partially modified enzyme showed an increase in the Km for Ado from 14 to 55
      microM. Furthermore, the inability of the modified enzyme to bind to 5'-AMP
      Sepharose 4B affinity column provided additional evidence that modification is
      attended by decrease in affinity of the enzyme for Ado. The results are
      consistent with the interpretation that modification of the active-site arginine
      residue affects activity by interfering with the binding of the substrate to the
      active site.

PMID- 8135735
TI  - Structure identifiability in metabolic pathways: parameter estimation in models
      based on the power-law formalism.
AB  - An important step in understanding a metabolic pathway is to identify its
      structure, in terms of the flow of material and information. In pursuing this
      goal, the available information for a given system is usually obtained from
      experiments in vitro and comes from different sources. Frequently, the final set
      of regulatory signals acting in the system in vivo is unclear, and some kind of
      test is needed on the intact system. Besides defining an appropriate experimental
      approach, identification of the regulatory pattern needs a theoretical framework
      in which the different experimental measurements can be evaluated and a final
      picture can be agreed on. Mathematical approaches based on sensitivity
      coefficients provide a useful tool for addressing this problem. Within this
      framework, the appropriate parameters are related to both the structure of the
      reaction network and the signals that regulate the target system. Thus the
      identification of the regulatory structure can be related to the estimation of
      the appropriate set of parameters. In pursuing this goal, we will show the
      limitations of using steady-state measurements and the usefulness of using
      dynamic data. We suggest a way to test the regulatory pattern in a given
      metabolic pathway by combining both kinds of data, and we show, by using a
      reference system, the potential of the method suggested.

PMID- 8135736
TI  - Enzyme-enzyme interactions and metabolite channelling: alternative mechanisms and
      their evolutionary significance.
AB  - Metabolite channelling may result from different kinetic mechanisms in which
      enzyme-enzyme interactions occur, so that intermediates are not released into the
      bulk solution and cannot be used by enzymes outside the channel. From an
      evolutionary point of view, the emergence of such mechanisms may provide new
      functional possibilities for the system, which would result in a selective
      advantage. Hence, it would be useful to evaluate the objective advantages
      provided by the various options by considering different criteria for functional
      effectiveness. Following this strategy, the goal of this paper is to compare a
      model for a free-diffusion two-enzyme system with two different models with
      inclusion of enzyme-enzyme interactions. In addition, models with simultaneous
      free and interacting branches are also analysed, and their advantages or
      disadvantages are presented. Basic guidelines are suggested that help in
      predicting the occurrence of specific mechanisms in different circumstances, and
      provide theoretical evidence in support of the hypothesis that no single solution
      simultaneously optimizes all the possible desired properties of the system.

PMID- 8135737
TI  - Regulation of lipoprotein lipase activity and mRNA in the mammary gland of the
      lactating mouse.
AB  - We examined the effects of reproductive stage and fasting on lipoprotein lipase
      (LPL) activity and mRNA in the mouse mammary gland. Heparin-releasable and cell
      associated LPL activity rose immediately after birth, followed 1-2 days later by
      an increase in LPL mRNA. Fasting decreased LPL activity in the mammary gland at
      all reproductive stages. During lactation, both milk and heparin-releasable LPL
      were substantially decreased by an overnight fast, whereas cell-associated LPL
      was less affected and LPL mRNA did not change. These studies indicate that the
      extracellular, heparin-releasable, fraction of mammary LPL activity responds most
      rapidly to alterations in physiological state, usually accompanied by smaller
      changes in cellular enzyme activity. Changes in the level of LPL mRNA were seen
      only during the transition from pregnancy to lactation, and these tended to
      follow, rather than precede, changes in enzyme activity. We conclude that in the
      mammary gland as in adipose tissue, LPL is regulated primarily at the
      translational and post-translational level.

PMID- 8135738
TI  - Electron transfer from Phanerochaete chrysosporium cellobiose oxidase to equine
      cytochrome c and Pseudomonas aeruginosa cytochrome c-551.
AB  - The electron-transfer reactions of cellobiose oxidase (CBO) have been
      investigated by conventional and by rapid-scan stopped-flow spectroscopy at pH
      6.0. Analysis of the absorbance/time/wavelength matrix by Singular Value
      Decomposition (SVD) confirms earlier studies showing that cellobiose rapidly
      reduces the flavin group (7.7 s-1; cellobiose, 100 microM) which in turn slowly
      (0.2 s-1) reduces the cytochrome b moiety. In the presence of CBO, cellobiose
      reduces cytochromes c in a reaction that does not depend on oxygen or superoxide.
      The rate limit for this process is independent of the source of the cytochromes c
      and is identical with the rate of cytochrome b reduction. Rapid-mixing
      experiments show that cytochrome b may donate electrons very rapidly to either
      mammalian cytochrome c or bacterial cytochrome c-551. The reactions were second
      order (kc = 1.75 x 10(7) M-1 x s-1; kc-551 = 4.3 x 10(6) M-1 x s-1; pH 6.0, 21
      degrees C and I0.064) and strongly ionic-strength (I)-dependent: kc decreasing
      with I and kc-551 increasing with I. These results suggest the electron-transfer
      site near cytochrome b bears a significant negative charge. Equilibrium gel
      chromatography confirms that CBO oxidase and positively charged mammalian
      cytochrome c make stable complexes. These results are discussed in terms of a
      model suggesting an electron-transfer role for cytochrome b in vivo, possibly
      connected with radical-mediated cellulose breakdown.

PMID- 8135739
TI  - Bradykinin-induced growth inhibition of normal rat kidney (NRK) cells is
      paralleled by a decrease in epidermal-growth-factor receptor expression.
AB  - Normal rat kidney fibroblasts, grown to density arrest in the presence of
      epidermal growth factor (EGF), can be induced to undergo phenotypic
      transformation by treatment with transforming growth factor beta or retinoic
      acid. Here we show that bradykinin blocks this growth-stimulus-induced loss of
      density-dependent growth arrest by a specific receptor-mediated mechanism. The
      effects of bradykinin are specific, and are not mimicked by other
      phosphoinositide-mobilizing agents such as prostaglandin F2 alpha. Northern-blot
      analysis and receptor-binding studies demonstrate that bradykinin also inhibits
      the retinoic acid-induced increase in EGF receptor levels in these cells. These
      studies provide additional evidence that EGF receptor levels modulate EGF-induced
      expression of the transformed phenotype in these cells.

PMID- 8135740
TI  - Inhibition of serine/threonine protein phosphatases promotes opening of voltage
      activated L-type Ca2+ channels in insulin-secreting cells.
AB  - The biological activity of many proteins, including voltage-sensitive ion
      channels, is controlled by their state of phosphorylation. Ca2+ influx through
      voltage-activated L-type Ca2+ channels serves as the major stimulatory signal in
      insulin-secreting cells. We have now investigated the extent to which Ca2+
      handling in clonal insulin-secreting RiNm5F cells was affected by okadaic acid,
      an inhibitor of various serine/threonine protein phosphatases. Whole-cell patch
      clamp experiments showed that okadaic acid generated an increase in membrane
      current, suggesting that it promotes Ca2+ influx through L-type voltage-gated
      Ca2+ channels probably by modifying their phosphorylation state. Okadaic acid was
      found to provoke a transient rise in the cytoplasmic free Ca2+ concentration
      ([Ca2+]i) but had no further effect on the K(+)-induced increase. The Ca2+
      transient induced by okadaic acid was dependent on the presence of extracellular
      Ca2+ and was abolished by D600, a blocker of voltage-activated L-type Ca2+
      channels. Concomitant with the rise in [Ca2+]i, okadaic acid induced insulin
      secretion, a phenomenon that was also dependent on extracellular Ca2+. It is
      proposed that hyperphosphorylation of voltage-activated L-type Ca2+ channels in
      insulin-secreting cells lowers the threshold potential for their activation.

PMID- 8135741
TI  - Effects of oxidative stress on expression of extracellular superoxide dismutase,
      CuZn-superoxide dismutase and Mn-superoxide dismutase in human dermal
      fibroblasts.
AB  - To determine the effect of oxidative stress on expression of extracellular
      superoxide dismutase (EC-SOD), CuZn-SOD and Mn-SOD, two fibroblast lines were
      exposed for periods of up to 4 days to a wide concentration range of oxidizing
      agents: xanthine oxidase plus hypoxanthine, paraquat, pyrogallol, alpha
      naphthoflavone, hydroquinone, catechol, Fe2+ ions, Cu2+ ions, buthionine
      sulphoximine, diethylmaleate, t-butyl hydroperoxide, cumene hydroperoxide,
      selenite, citiolone and high oxygen partial pressure. The cell lines were
      cultured both under serum starvation and at a serum concentration that permitted
      growth. Under no condition was there any evidence of EC-SOD induction. Instead,
      the agents uniformly, dose-dependently and continuously reduced EC-SOD
      expression. We interpret the effect to be due to toxicity. Enhancement of the
      protection against oxidative stress by addition of CuZn-SOD, catalase and low
      concentrations of selenite did not influence the expression of any of the SOD
      isoenzymes. Removal of EC-SOD from cell surfaces by heparin also did not
      influence SOD expression. Mn-SOD was moderately induced by high doses of the
      first 11 oxidants. Apart from reduction at high toxic doses, there were no
      significant effects on the CuZn-SOD activity by any of the treatments. Thus EC
      SOD, previously shown to be profoundly influenced by inflammatory cytokines, was
      not induced by its substrate or other oxidants. In a similar fashion, Mn-SOD,
      previously shown to be greatly induced and depressed by cytokines, was only
      moderately influenced by oxidants. We suggest that the regulation of these SOD
      isoenzymes in mammalian tissues primarily occurs in a manner co-ordinated by
      cytokines, rather than as a response of individual cells to oxidants.

PMID- 8135742
TI  - Structural characterization of the carbohydrates of the rat ovarian luteinizing
      hormone/chorionic gonadotropin receptor.
AB  - The numbers and types of oligosaccharide present on the rat ovarian luteinizing
      hormone (LH)/chorionic gonadotropin (CG) receptor were determined by treating
      radiolabelled purified receptors with glycosidases and examining the changes in
      electrophoretic mobility and number of radiolabelled bands on SDS/PAGE. The
      purified receptor was also transferred to nitrocellulose after SDS/PAGE and
      probed with digoxigenin-labelled lectins. The following conclusions were drawn:
      (1) the rat ovarian LH/CG receptor contains at least two complex-type N-linked
      oligosaccharide chains, of which one is biantennary and the rest multiantennary.
      (2) The N-linked chains terminate in either unsubstituted galactose or sialic
      acid linked alpha 2-3 or alpha 2-6 to the penultimate galactose. (3) The N-linked
      oligosaccharides also contain internal poly(N-acetyl-lactosamine) sequences and
      fucose-linked alpha 1-6 to the proximal N-acetylglucosamine. (4) No O-linked
      carbohydrate moieties are present on the receptor molecule.

PMID- 8135743
TI  - Determination of control coefficients in intact metabolic systems.
AB  - The control structure of a metabolic system can in principle be determined
      without the need for purification of the component enzymes and study of their
      kinetic properties, provided that their activities can be perturbed by amounts
      sufficient to produce measurable changes in the steady-state variables, i.e. the
      fluxes through the system and the concentrations of the intermediates. Each
      perturbation is characterized in terms of the co-response coefficients of all
      pairs of variables, i.e. the slopes of the lines produced when the logarithm of
      one variable is plotted against the logarithm of another, both varying in
      response to the same perturbation. If all the co-response coefficients are
      assembled into a matrix, the inverse of this matrix can be transformed into a
      matrix containing all the component elasticities, which can be inverted to
      provide the complete matrix of control coefficients. In a simple three-enzyme
      pathway studied, the analysis proves not to require unrealistically high accuracy
      in the original co-response measurements: even with errors with standard
      deviation +/- 5.77 degrees in the angles to the horizontal of the lines in the co
      response plots (equivalent at best to errors of +/- 20% in the corresponding co
      response coefficients), the final control coefficient matrix may be adequate for
      assessing the control structure of the system. Examination of literature data
      from studies of mitochondrial respiration and of gluconeogenesis indicates that
      considerably higher precision than this is achievable.

PMID- 8135744
TI  - Calcium promotes membrane association of reticulocyte 15-lipoxygenase.
AB  - The reticulocyte 15-lipoxygenase (linoleate:oxygen oxidoreductase, EC 1.13.11.12)
      is implicated in oxidative damage to reticulocyte mitochondria before their
      elimination by degradation during maturation to the erythrocyte. A proportion of
      the 15-lipoxygenase sediments with the mitochondrial-rich stromal fraction of
      density-gradient-fractionated rabbit reticulocytes suggesting a physical
      association with mitochondria before their elimination. Ca2+ promotes binding of
      reticulocyte 15-lipoxygenase to isolated rat liver and reticulocyte mitochondria
      and 15-lipoxygenase-mediated lipid peroxidation of mitochondrial lipids and free
      linoleic acid. Association of reticulocyte 15-lipoxygenase with isolated
      mitochondria is not simply a consequence of Ca(2+)-induced swelling, but implies
      that Ca2+ mediates translocation of soluble lipoxygenase to mitochondrial
      membranes. Therefore, Ca2+ may have an important physiological role in the
      regulation of 15-lipoxygenase-mediated targeting of reticulocyte mitochondria for
      degradation.

PMID- 8135745
TI  - Isolation and characterization of two mouse Pi-class glutathione S-transferase
      genes.
AB  - Pi-class glutathione S-transferases (GSTs) play an important role in the
      detoxification of chemical toxins and mutagens and are implicated in neoplastic
      development and drug resistance. In all species characterized to date, only one
      functional Pi-class GST gene has been described. In this report we have
      identified two actively transcribed murine Pi-class GST genes, Gst p-1 and Gst p
      2. The coding regions of Gst p-1 and the mouse Pi-class GST cDNA (GST-II)
      reported by Hatayama, Satoh and Satoh (1990) (Nucleic Acids Res. 18, 4606) are
      identical, whereas Gst p-2 encodes a protein that has not been described
      previously. The two genes are approximately 3 kb long and contain seven exons
      interrupted by six introns. In addition to a TATA box and a sequence motif
      matching the phorbol-ester-responsive element, the promoters of Gst p-1 and Gst p
      2 exhibit one and two G+C boxes (GGGCGG) respectively. The cDNAs of the two genes
      were isolated from total liver RNA using reverse PCR. The peptide sequence
      deduced from the cDNAs share 97% identity and differ in six amino acids. Both
      genes are transcribed at significantly higher levels in male mouse liver than in
      female, and Gst p-1 mRNA is more abundant in both sexes than Gst p-2.

PMID- 8135746
TI  - Microcrystals of the beta 1 isoenzyme of protein kinase C: an electron
      microscopic study.
AB  - Microcrystals of protein kinase C beta 1 have been grown from solutions of
      poly(ethylene glycol). Image analysis of electron micrographs of the protein
      crystals, which diffracted to 5.0 nm, revealed p3 symmetry with a unit cell of
      about 10.3 nm x 10.3 nm. The electron stain-excluding densities showed a three
      domain ring structure in projection, giving kidney bean-shaped molecules of about
      7.0 nm x 4.5 nm diameter, packed as trimers. The implications of these
      observations for the function of the enzyme are discussed.

PMID- 8135747
TI  - Characterization and kinetic analysis of the intracellular domain of human
      protein tyrosine phosphatase beta (HPTP beta) using synthetic phosphopeptides.
AB  - The intracellular domain of human protein tyrosine phosphatase beta (HPTP beta)
      (44 kDa) was expressed in bacteria, purified using epitope 'tagging'
      immunoaffinity chromatography, and characterized with respect to kinetic profile,
      substrate specificity and potential modulators of enzyme activity. A chromogenic
      assay based on the Malachite Green method was employed for the detection of
      inorganic phosphate (Pi) released from phosphopeptides by HPTP beta. This assay,
      modified so as to improve its sensitivity, was adapted to a 96-well microtitre
      plate format, and provided linear detection between 50 and 1000 pmol of Pi. The
      cytoplasmic domain of HPTP beta was strongly inhibited by vanadate, molybdate,
      heparin, poly(Glu, Tyr) (4:1) and zinc ions. In order to explore the substrate
      preferences of this PTPase, we generated 13-residue synthetic phosphotyrosine
      containing peptides that corresponded to sites of physiological tyrosine
      phosphorylation. HPTP beta demonstrated kcat. values between 76 and 258 s-1 using
      four different phosphopeptides. The substrate preference of HPTP beta was in the
      order srcTyr-527 > PDGF-RTyr-740 > ERK1Tyr-204 >> CSF-1RTyr-708 with Km values
      ranging from 140 microM to greater than 10 mM. The variations in affinity were
      probably due to differences among the four phosphopeptides compared, particularly
      with respect to the character of the charged amino acids flanking the
      phosphotyrosine residue.

PMID- 8135748
TI  - The gelatin-binding site of human 72 kDa type IV collagenase (gelatinase A).
AB  - To identify structures critical for gelatin-binding of 72 kDa type IV collagenase
      (gelatinase A), fragments of this metalloproteinase have been expressed in
      Escherichia coli and assayed for their gelatin affinity. Each of the three
      fibronectin-related type II domains was found to have affinity for gelatin.
      Fragments containing all three tandem type II domains had significantly stronger
      affinity than any of the constituent units, indicating that they co-operate to
      form the high-affinity gelatin-binding site. Competition experiments have also
      shown that gelatinase A binds more tightly to gelatin than fibronectin and can
      displace the latter from denatured collagen.

PMID- 8135749
TI  - The effect of beta,beta'-tetramethylhexadecanedioic acid (MEDICA 16) on plasma
      very-low-density lipoprotein metabolism in rats: role of apolipoprotein C-III.
AB  - Short term treatment of rats with beta,beta'-tetramethylhexadecanedioic acid
      (MEDICA 16) results in a pronounced decrease in plasma very-low-density
      lipoprotein (VLDL) cholesterol and VLDL triacylglycerol, previously ascribed to a
      decrease in liver VLDL production [Bar-Tana, Rose-Kahn, Frenkel, Shafer and
      Fainaru (1988) J. Lipid Res. 29, 431-441]. The hypolipidaemic effect of MEDICA 16
      was further analysed here by monitoring plasma VLDL clearance and its hepatic
      uptake. VLDL triacylglycerol and VLDL apolipoprotein (apo) B fractional clearance
      rates were increased 7-8-fold in MEDICA 16-treated rats. The increase in the
      fractional clearance rate of plasma VLDL was essentially eliminated by functional
      hepatectomy. It was accounted for by activation of plasma VLDL uptake by the
      liver being completed during the first 4 min after the injection of the VLDL
      label and before commencement of uptake in non-treated animals. The
      hypolipidaemic effect of MEDICA 16 was accompanied by a 3.5-fold decrease in
      plasma apoC-III, but plasma apoC-III clearance remained unaffected by MEDICA 16.
      MEDICA 16-induced premature hepatic uptake of plasma VLDL due to suppression of
      apoC-III production may thus account for enhancement of plasma VLDL clearance in
      treated animals.

PMID- 8135750
TI  - Folate-deficiency-induced homocysteinaemia in rats: disruption of S
      adenosylmethionine's co-ordinate regulation of homocysteine metabolism.
AB  - In a recent hypothesis [Selhub and Miller (1992) Am. J. Clin. Nutr. 55, 131-138],
      we proposed that homocysteinaemia arises from an interruption in S
      adenosylmethionine's (AdoMet) coordinate regulation of homocysteine metabolism.
      The present study was undertaken to test a prediction of this hypothesis, that
      homocysteinaemia due to folate deficiency results from impaired homocysteine
      remethylation due to the deficiency and impaired synthesis of AdoMet, with the
      consequent inability of this metabolite to function as an activator of
      homocysteine catabolism through cystathionine synthesis. Rats were made folate
      deficient by feeding them with a folate-free amino-acid-defined diet supplemented
      with succinylsulphathiazole. After 4 weeks, the deficient rats exhibited a 9.8
      fold higher mean plasma homocysteine concentration and a 3.2-fold lower mean
      hepatic AdoMet concentration compared with folate-replete controls. Subsequent
      supplementation for 3 weeks of the folate-deficient rats with increasing levels
      of folate in the diet resulted in graded decreases in plasma homocysteine levels,
      accompanied by graded increases in hepatic AdoMet levels. Thus plasma
      homocysteine and hepatic AdoMet concentrations were inversely correlated as
      folate status was modified. In a second experiment, the elevation of plasma
      homocysteine in the deficient rats was found to be reversible within 3 days by
      intraperitoneal injections of ethionine. This effect of ethionine is thought to
      be exerted through S-adenosylethionine, which is formed in the liver of these
      rats. Like AdoMet, S-adenosylethionine is an activator of cystathionine beta
      synthase and will effectively promote the catabolism of homocysteine through
      cystathionine synthesis. In crude liver homogenates of the rats treated with
      ethionine, cystathionine beta-synthase activity was 3-fold higher than that
      measured in homogenates from vehicle-treated controls.

PMID- 8135751
TI  - Transcriptional regulation of the tartrate-resistant acid phosphatase (TRAP) gene
      by iron.
AB  - Tartrate-resistant acid phosphatase (TRAP) was first identified in cells from
      patients with hairy cell leukaemia. Subsequently, it has been found in other
      leukaemias, B-lymphoblastoid cell lines, osteoclasts and subsets of normal
      lymphocytes, macrophages, and granulocytes. Recent data indicate that TRAP and
      porcine uteroferrin, a placental iron-transport protein, represent a single gene
      product. However, the intracellular role of TRAP is unknown. We used a full
      length human placental TRAP cDNA probe to examine TRAP expression in human
      peripheral mononuclear cells (PMCs). TRAP mRNA increased 50-75-fold after 24 h in
      unstimulated PMC cultures. Cell-fractionation experiments indicated that
      monocytes were the main cell population accounting for increased TRAP mRNA
      transcripts, and this was confirmed by histochemical staining for TRAP enzyme
      activity. Because expression of other iron-binding and -transport proteins is
      controlled by iron availability, we examined the role of iron in regulating TRAP
      expression. Increase of TRAP mRNA transcripts in PMCs was inhibited by 50 microM
      desferrioxamine, a potent iron chelator. The 5' flanking region of the TRAP gene
      was cloned from a mouse genomic library. In preliminary transient transfection
      experiments, it was determined that the 5'-flanking region of the TRAP gene
      contained iron-responsive elements. Therefore, a series of stably transfected HRE
      H9 cell lines was developed bearing genetic constructs containing various
      segments of the murine TRAP 5' promoter region driving a luciferase reporter
      gene. Treatment of transfectants with 100 micrograms/ml iron-saturated human
      transferrin (FeTF) was performed to assess iron responsiveness of the constructs.
      Constructs containing a full-length TRAP promoter (comprising base pairs -1846 to
      +2) responded to FeTF with a 4-5-fold increase of luciferase activity whereas
      constructs containing only base pairs -363 to +2 of the TRAP promoter did not
      respond. Constructs containing 1240 or 881 bp of the TRAP promoter gave only a
      1.5- to 2-fold increase of luciferase activity with FeTF. In all cases, increase
      of luciferase activity was blocked by desferrioxamine. Cells transfected with
      another luciferase construct driven by a simian virus 40 promoter did not show
      any increase of luciferase activity with FeTF. These data indicate that
      expression of TRAP is regulated by iron and that this regulation is exerted at
      the level of gene transcription. The transfection experiments also suggest that
      the region of the TRAP 5'-flanking sequence between base pairs -1846 and -1240
      contains an iron regulatory element.

PMID- 8135752
TI  - The role of His66 and His72 in the reaction mechanism of bovine liver low-M(r)
      phosphotyrosine protein phosphatase.
AB  - Site-directed mutagenesis of a synthetic gene coding for low-M(r) phosphotyrosine
      protein phosphatase from bovine liver has been carried out. The two histidine
      residues in the enzyme have been mutated to glutamine; both single and double
      mutants were produced. The mutated and non-mutated sequences have been expressed
      in Escherichia coli as fusion proteins, in which the low-M(r) phosphotyrosine
      protein phosphatase was linked to the C-terminal end of the maltose-binding
      protein. The fusion enzymes were easily purified by single-step affinity
      chromatography. The mutants were studied for their kinetic properties. Both
      single mutants showed decreased kcat. values (30 and 7% residual activities for
      His66 and His72 respectively), and alterations of the Ki values relative to four
      competitive inhibitors were observed. The kinetic mechanism of p-nitrophenyl
      phosphate hydrolysis in the presence of both single mutants was determined and
      compared with that of the non-mutated enzyme. The rate-determining step of the
      catalytic process of the His66-->Gln mutant was the same as that found for non
      mutated enzyme, whereas for the His72-->Gln mutant, both the kinetic constant of
      the step that causes the formation of a phosphoenzyme covalent intermediate, and
      the kinetic constant of the step that causes the dephosphorylation of the enzyme
      covalent intermediate, determined the kcat. value. This observation was confirmed
      by phosphoenzyme covalent intermediate trapping experiments. The participation of
      both histidine residues (His66 and His72) at the active site is strongly
      suggested by the results of diethyl pyrocarbonate inactivation of both single
      mutants, each containing a single histidine residue. Both mutants are completely
      inactivated by diethyl pyrocarbonate treatment; the competitive inhibitor Pi
      protects both mutants from inactivation. The His66/His72 double mutant was
      completely inactive.

PMID- 8135753
TI  - Covalent structure of bovine brain calreticulin.
AB  - The covalent structure of bovine brain calreticulin, a major Ca(2+)-binding
      protein in the lumen of the endoplasmic reticulum, was determined by analysis of
      the purified protein. The protein consisted of 400 amino acids, with an N-linked
      oligosaccharide attached to the polypeptide chain. The polypeptide sequence
      determined was compatible with the sequence of calreticulin deduced from cDNA of
      different sources, with a number of differences presumably due to species
      specific amino acid substitutions. The protein retained the C-terminal
      tetrapeptide, KDEL, involved in retention of proteins resident in the endoplasmic
      reticulum, whereas the N-terminal signal peptide predicted from the cDNA sequence
      had been removed in the purified protein. The bovine brain protein contained a
      high-mannose type of oligosaccharide attached to Asn162, which is typical of
      resident endoplasmic reticulum proteins. The carbohydrate moiety was
      heterogeneous and had the composition GlcNAc2Man4-9, of which GlcNAc2Man5 was the
      most abundant in the bovine brain preparation. Glycosylation of calreticulin,
      however, appeared to be a species-specific modification, as Asn162 is replaced by
      Asp in the sequences already determined for a number of species. Analysis of the
      purified protein also identified an intramolecular disulphide bridge between
      Cys120 and Cys146.

PMID- 8135754
TI  - Elevated protein tyrosine phosphatase activity and increased membrane viscosity
      are associated with impaired activation of the insulin receptor kinase in old
      rats.
AB  - Insulin resistance is very common in the elderly, and may be associated with
      glucose intolerance or frank diabetes. In previous studies we demonstrated that
      insulin resistance in old Wistar rats is associated with decreased
      autophosphorylation and activation of the hepatic insulin receptor kinase (IRK)
      in vivo. We now show that this defect can be reproduced in vitro, where the
      extent of insulin-induced activation of IRK in liver membranes of old rats was
      decreased by approximately 50% compared with young controls. The defect could be
      largely abolished after solubilization of the membranes with Triton X-100. We
      also show that: (a) the viscosity of membranes from the old rats was
      significantly (P < 0.001, n = 4) higher (by 15%) compared with young controls;
      (b) incubation of plasma membranes from old animals with lecithin liposomes,
      which lowered their cholesterol levels, partially abolished the defect in IRK
      activation; and (c) Triton extracts of liver membranes prepared from old rats did
      not interfere with the activation of IRK derived from young controls.
      Additionally, non-membrane components did contribute to the development of this
      defect. We observed a significant (approximately 30%) (P < 0.001, n = 18)
      elevation of cytosolic protein tyrosine phosphatase (PTP) activity directed
      against the beta subunit of the insulin receptor in livers of old rats. No such
      elevation of PTP activity could be demonstrated with synthetic substrates. Our
      findings are consistent with a model in which increased membrane viscosity as
      well as enhancement of a cytosolic PTP activity both markedly inhibit the
      activation in vivo of the hepatic IRK in old animals.

PMID- 8135755
TI  - Protein kinase C-dependent prostaglandin production mediates angiotensin II
      induced atrial-natriuretic peptide release.
AB  - The respective roles of protein kinase C (PKC) and endogenous prostaglandin
      formation in angiotensin II (Ang II)-induced myocardial secretion of atrial
      natriuretic peptide (ANP) was studied in cultured, spontaneously beating,
      neonatal-rat cardiomyocytes. Incubation of cardiomyocytes with 0.1 microM Ang II
      led to a rapid but transient increase in particulate-bound PKC activity, a
      response accompanied by marked increases in cellular 6-oxo-prostaglandin F1 alpha
      (6-oxo-PGF1 alpha) generation and ANP secretion. A role for PKC in Ang II-induced
      6-oxo-PGF1 alpha formation and ANP secretion was apparent, insofar as both
      responses were suppressed in the presence of the PKC inhibitors staurosporine (1
      microM) and CGP 41251 (1 microM), as well as in cells in which PKC had been
      previously down-regulated by pretreatment with phorbol diester. Furthermore, Ang
      II-induced 6-oxo-PGF1 alpha production was found to be strongly correlated with
      Ang II-induced ANP release (r = 0.87, P < 0.001, n = 6), indicating a role for
      prostacyclin (PGI2) in Ang II-induced ANP secretion in these cells. This
      hypothesis was confirmed by finding that both Ang II-induced 6-oxo-PGF1 alpha
      production and ANP release were abolished in the presence of the respective
      phospholipase A2 and cyclo-oxygenase inhibitors quinacrine (10 microM) and
      indomethacin (10 microM), whereas exogenously applied PGI2 (1 microM) and
      prostaglandin E2 (0.1 microM) mimicked Ang II-induced ANP secretion in this
      system. Taken together, these results suggest that Ang II induces ANP secretion
      in spontaneously beating rat cardiomyocytes via a PKC-dependent autocrine pathway
      involving a cyclo-oxygenase product and a yet-to-be-identified myocardial
      prostanoid receptor.

PMID- 8135756
TI  - Further thermal characterization of an aspartate aminotransferase from a
      halophilic organism.
AB  - Aspartate aminotransferase (AspAT, EC 2.6.1.1) from the halophilic
      archaebacterium Haloferax mediterranei was purified [Muriana, Alvarez-Ossorio and
      Relimpio (1991) Biochem. J. 278, 149-154] and further characterization of the
      effects of temperature on the activity and stability of the halophilic AspAT were
      carried out. The halophilic transaminase is most active at 65 degrees C and
      stable at high temperatures, under physiological or nearly physiological
      conditions (3.5 M KCl, pH 7.8). Thermal inactivation (60-85 degrees C) of the
      halophilic AspAT followed first-order kinetics, 2-oxoglutarate causing a shift of
      the thermal inactivation curves to higher temperatures. The salt concentration
      affected the thermal stability of the halophilic transaminase at 60 degrees C,
      suggesting that disruption of hydrophobic interactions may play an important role
      in the decreased thermal stability of the enzyme.

PMID- 8135757
TI  - Identification of serines-967/968 in the juxtamembrane region of the insulin
      receptor as insulin-stimulated phosphorylation sites.
AB  - A line of Chinese hamster ovary cells overexpressing protein kinase C alpha was
      transfected with cDNAs encoding either the wild-type human insulin receptor or
      one of two mutant insulin receptors with either Ser-967 and -968 or -974 and -976
      in the juxtamembrane region changed to alanine. Both mutant receptors exhibited
      normal insulin-activated tyrosine kinase activity as assessed by either
      autophosphorylation or insulin-stimulated increases in anti-phosphotyrosine
      precipitable phosphatidylinositol 3-kinase. The wild-type and mutant insulin
      receptors were also examined for serine and threonine phosphorylation in response
      to insulin and activation of protein kinase C. To visualize Ser/Thr
      phosphorylation sites of the receptor better in response to insulin, the receptor
      from in vivo-labelled insulin-treated cells was first treated with a tyrosine
      specific phosphatase to remove all tyrosine phosphorylation. Phosphopeptides from
      the three receptors were analysed by high-percentage polyacrylamide/urea gel
      electrophoresis and two-dimensional t.l.c. The mutant receptor lacking Ser-967
      and -968 but not the mutant lacking Ser-974 and -976 was found to be missing
      phosphorylated peptides in response to insulin and, to a lesser extent, after
      activation of protein kinase C. However, the insulin-stimulated increase in anti
      phosphotyrosine-precipitable phosphatidylinositol 3-kinase was inhibited to the
      same extent by activation of protein kinase C in cells expressing the two mutant
      receptors as in cells expressing the wild-type receptor. These results indicate
      that these four serine residues in the juxtamembrane region are not major
      regulatory sites of the intrinsic tyrosine kinase activity of the insulin
      receptor by protein kinase C, although Ser-967 and/or -968 appear to be
      phosphorylated in response to insulin.

PMID- 8135758
TI  - Prostaglandin F2 alpha-stimulated phospholipase D activation in osteoblast-like
      MC3T3-E1 cells: involvement in sustained 1,2-diacylglycerol production.
AB  - In [3H]myristic acid-labelled osteoblast-like MC3T3-E1 cells, prostaglandin F2
      alpha (PGF2 alpha)-induced PLD activity was assessed by measuring the
      [3H]phosphatidylethanol (PEt) formation in the presence of ethanol. Inhibition of
      the increase in intracellular Ca2+ concentration ([Ca2+]i) by U73122, an
      inhibitor of phosphoinositide-specific phospholipase C (PI-PLC), or chelation of
      extracellular Ca2+ with EGTA or of intracellular Ca2+ with BAPTA, suppressed PGF2
      alpha-induced phospholipase D (PLD) activation. Neither protein kinase C (PKC)
      inhibitors nor PKC down-regulation with phorbol 12-myristate 13-acetate affected
      PGF2 alpha-induced [3H]PEt formation. In permeabilized cells, guanosine 5'-[gamma
      thio]triphosphate enhanced PGF2 alpha 's potency in [3H]PEt formation in the
      presence of Ca2+. The pretreatment of intact cells with pertussis toxin failed to
      inhibit PGF2 alpha-induced [3H]PEt formation. PGF2 alpha caused a biphasic
      production of [3H]1,2-diacylglycerol ([3H]1,2-DAG) in [3H]glycerol-labelled
      cells. The initial transient phase was decreased by U73122, whereas the late
      sustained phase was decreased by ethanol and the phosphatidic acid
      phosphohydrolase inhibitor, propranolol. From these results, it was suggested
      that PGF2 alpha-induced PLD activation was mediated by the dual control of the
      [Ca2+]i increase due to PI-PLC activation and activation of pertussis-toxin
      insensitive G-protein, but not mediated by PKC, and also that PLD activation was
      involved in the late sustained 1,2-DAG generation in MC3T3-E1 cells.

PMID- 8135759
TI  - Polyamine-induced Z-DNA conformation in plasmids containing (dA-dC)n.(dG-dT)n
      inserts and increased binding of lupus autoantibodies to the Z-DNA form of
      plasmids.
AB  - Blocks of potential Z-DNA-forming (dA-dC)n.(dG-dT)n sequences are ubiquitous in
      eukaryotic genomes. We examined whether naturally occurring polyamines,
      putrescine, spermidine and spermine, could provoke the Z-DNA conformation in
      plasmids pDHf2 and pDHf14 with 23 and 60 bp inserts respectively of (dA-dC)n.(dG
      dT)n sequences using an e.l.i.s.a. Spermidine and spermine could provoke Z-DNA
      conformation in these plasmids, but putrescine was ineffective. For pDHf2 and
      pDHf14, the concentration of spermidine at the midpoint of B-DNA to Z-DNA
      transition was 25 microM, whereas that of spermine was 16 microM. Polyamine
      structural specificity was evident in the ability of spermidine homologues to
      induce Z-DNA. Inorganic cations, Co(NH3)6(3+) and Ru(NH3)6(3+), were ineffective.
      Our experiments also showed increased binding of anti-DNA autoantibodies from
      lupus patients as well as autoimmune MRL-lpr/lpr mice to pDHf2 and pDHf14 in the
      presence of polyamines. These data demonstrate that small blocks of (dA-dC)n.(dG
      dT)n sequences could assume the Z-DNA conformation in the presence of natural
      polyamines. Increased concentrations of polyamines in the sera of lupus patients
      might facilitate immune complex-formation involving circulating DNA and anti-Z
      DNA antibodies.

PMID- 8135760
TI  - Stimulation of high-affinity GTPase activity and cholera toxin-catalysed [32P]ADP
      ribosylation of Gi by lysophosphatidic acid (LPA) in wild-type and alpha 2C10
      adrenoceptor-transfected Rat 1 fibroblasts.
AB  - Lysophosphatidic acid (LPA) stimulated high-affinity GTPase activity in membranes
      of Rat 1 fibroblasts. This effect was dose-dependent, with maximal effects at 10
      microM LPA, and was attenuated by pertussis toxin but not by cholera toxin
      pretreatment of the cells, indicating that the effect was likely to be produced
      by a Gi-like G-protein. LPA stimulation of high-affinity GTPase was also observed
      in a clone of Rat 1 fibroblasts that had been transfected to express the human
      alpha 2C10 adrenoceptor. The alpha 2 adrenoceptor agonist UK14304 also stimulated
      high-affinity GTPase activity in membranes of these cells, but not in parental
      Rat 1 cells. LPA was also able to promote cholera toxin-catalysed [32P]ADP
      ribosylation of Gi. This effect of LPA was also prevented by pretreatment of the
      cells with pertussis toxin but not cholera toxin. LPA-stimulated cholera toxin
      catalysed [32P]ADP-ribosylation of Gi in membranes of the alpha 2C10 adrenoceptor
      expressing clone was additive with that produced by UK14304. Dose-response curves
      for LPA in the two assays of G-protein activation were coincident. The results
      presented herein demonstrate conclusively that the pertussis toxin-sensitive
      effects of LPA in Rat 1 fibroblasts and a clone of these cells expressing the
      alpha 2C10 adrenoceptor are produced directly by the activation of Gi.

PMID- 8135761
TI  - Interfacial hydrolysis of phosphatidylinositol 4-phosphate and
      phosphatidylinositol 4,5-bisphosphate by turkey erythrocyte phospholipase C.
AB  - The activity of a beta-isoform of phospholipase C (PLC) partially purified from
      turkey erythrocyte cytosol was assayed using phospholipid monolayers formed at an
      air-water interface. PLC was rapidly purified at least 8000-fold by a sequence of
      ion-exchange, hydrophobic and heparin chromatographies. 33P-labelled substrates
      were prepared using partially purified PtdIns kinase and PtdIns4P 5-kinases,
      respectively, and purified by h.p.l.c. using an amino-cyano analytical column.
      Using such 33P-labelled phosphoinositides of high specific radioactivity, PLC
      activity was monitored directly by measuring the loss of radioactivity from
      monolayers as a result of the release of inositol phosphates and their subsequent
      dissolution and quenching in the subphase. Under these conditions, PtdIns4P
      hydrolysis obeyed approximately first-order kinetics whereas PtdIns(4,5)P2
      hydrolysis was zero-order at least until 80% of the substrate had been degraded.
      PLC activity was markedly affected by the surface pressure of the monolayer, with
      reduced activity at extremes of initial pressure and with the most permissive
      pressures in the middle of the range investigated. The optimum surface pressure
      for hydrolysis of PtdIns4P was approx. 25 mN/m, but for PtdIns(4,5)P2 the maximum
      activity occurred at the markedly higher surface pressure of 30 mN/m. These data
      are discussed in terms of the substrate specificity and likely regulation of PLC
      beta isoforms engaged in degrading their substrate in biological membranes.

PMID- 8135762
TI  - Contribution of interactions with the core domain of hirudin to the stability of
      its complex with thrombin.
AB  - The importance of interactions with residues 15-21 in the core domain of hirudin
      for the formation of the complex with thrombin has been investigated by site
      directed mutagenesis. Contacts made by Leu-15 were found to be particularly
      important; replacement of this residue by alanine led to a decrease in the
      binding energy (delta delta Gbo) of 15 kJ.mol-1. Comparison with effects obtained
      in previous mutagenesis studies indicate that interactions with the side chain of
      Leu-15 contribute more to the stability of the complex than those of any other
      hirudin residues. Interactions with the side chains of Glu-17, Asn-20 and Val-21
      also contributed significantly to binding energy; the delta delta Gbo value for
      these mutations was between 3 and 6 kJ.mol-1. Examination of the crystal
      structure of the thrombin-hirudin complex suggested the possibility that ionic
      interactions that would increase binding energy could be engineered by mutating
      Ser-19, Asn-20 and Gln-49 to acidic residues. The stability of the thrombin
      hirudin complex was not, however, increased by these substitutions. The results
      obtained are discussed in terms of the crystal structure of the thrombin-hirudin
      complex.

PMID- 8135763
TI  - Limitations of the radioreceptor assay of inositol 1,4,5-trisphosphate in
      vanadate-treated cell suspensions.

PMID- 8135764
TI  - Differential repair of excision gaps generated by transposable elements of the
      'Ac family'.
AB  - Studies on transposable elements of the Ac family have led to different models
      for excision gap repair in either plants or Drosophila. Excision products
      generated by the plant transposable elements Ac and Tam3 imply a more or less
      straightforward ligation of broken ends; excision products of the Drosophila P
      element indicate the involvement of 'double-strand break' (DSB) repair. Recent
      findings that excision products of Ac and Tam3 can also contain traces of the
      element ends indicate, however, that DSB repair might be an alternative repair
      mechanism in plants. A functional DSB repair mechanism in plants can also be
      deduced from the observed rapid increases of Ac copy number during plant
      development and from the involvement of Ac in the generation of internal Ac
      deletions. On the other hand, alternative repair mechanisms may also be
      functional in Drosophila, because some of the 'footprints' generated upon P
      excision can be explained by a mechanism that has been postulated for excision
      gap repair in plants. It is concluded that plants and Drosophila can use similar
      repair mechanisms, but that the predominance of a certain repair mechanism is
      determined by the host.

PMID- 8135765
TI  - Intracellular pH regulation in the early embryo.
AB  - Intracellular pH (pHi) regulation is a homeostatic function of all cells.
      Additionally, the plasma membrane-based transporters controlling pHi are involved
      in growth factor activation, cell proliferation and salt transport--all processes
      active in early embryos. pHi regulation in the early embryos of many species
      exhibits unique features: in mouse preimplantation embryos, mechanisms for
      correcting excess acid apparently are inactive, while excess base is removed by
      the mechanism common in differentiated cells. Additionally, unlike differentiated
      cells, mouse preimplantation embryos are highly permeable to H+ until the
      blastocyst stage, where the epithelial cells surrounding the embryo are
      impermeable. In several non-mammalian species, of which the best-studied is sea
      urchin, cytoplasmic alkalinization at fertilization is necessary for development
      of the embryo, and elevated pHi must be maintained during early development.
      Thus, pHi regulatory mechanisms appear to be important for early embryo
      development in many species.

PMID- 8135766
TI  - Regulation of zygotic gene activation in the mouse.
AB  - Zygotic gene activation (ZGA) is the critical event that governs the transition
      from maternal to embryonic control of development. In the mouse, ZGA occurs
      during the 2-cell stage and appears to be regulated by the time following
      fertilization, i.e. a zygotic clock, rather than by progression through the first
      cell cycle. The onset of ZGA must depend on maternally inherited proteins, and
      post-translational modification of these maternally derived proteins is likely to
      play a role in ZGA. Consistent with this prediction is that protein
      phosphorylation catalyzed by the cAMP-dependent protein kinase is involved in ZGA
      and that protein synthesis is not required for ZGA. Recent results suggest that
      ZGA may occur earlier than previously thought, i.e. not during the 2-cell stage,
      but rather in G2 of the 1-cell embryo. Thus ZGA may comprise a period of minor
      gene activation in the 1-cell embryo that is followed by a period of major gene
      activation in the 2-cell embryo. Following ZGA, the expression of constitutively
      activated genes may require an enhancer.

PMID- 8135767
TI  - A signature for the HMG-1 box DNA-binding proteins.
AB  - A diverse group of DNA-binding regulatory proteins share a common structural
      domain which is homologous to the sequence of a highly conserved and abundant
      chromosomal protein, HMG-1. Proteins containing this HMG-1 box regulate various
      cellular functions involving DNA binding, suggesting that the target DNA
      sequences share a common structural element. Members of this protein family
      exhibit a dual DNA-binding specificity: each recognizes a unique sequence as well
      as a common DNA conformation. The highly conserved HMG-1/-2 proteins may modulate
      the binding of other HMG-1 box proteins to bent DNA. We examine the structural
      and functional relationships between the proteins, identify their signature and
      describe common features of their target DNA elements.

PMID- 8135768
TI  - Gene delivery to neurons: is herpes simplex virus the right tool for the job?
AB  - Herpes simplex virus (HSV)-derived vectors are currently being developed for the
      introduction of foreign DNA into neurons. HSV vectors can facilitate a range of
      molecular studies on postmitotic neurons and may ultimately be used for somatic
      cell gene therapy for certain neurologic diseases. In this article, the salient
      features of the pathologenesis and molecular biology of HSV relevant to its use
      as a vector are described, along with an overview of the methods used to derive
      these vectors. The accomplishments which have been made to date using the HSV
      vector system are discussed, with emphasis on the issues of this technology which
      remain to be addressed. HSV has the potential to be a most useful tool for
      neuronal cell transgenesis and it is likely that important neurobiological
      questions will be answered using this vector system.

PMID- 8135769
TI  - Telomeric DNA binding proteins.
AB  - The physical ends of eukaryotic chromosomes form a specialized nucleoprotein
      complex composed of DNA and DNA binding proteins. This nucleoprotein complex,
      termed the telomere, is essential for chromosome stability. In most organisms,
      the DNA portion of the nucleo-protein complex consists of simple tandem DNA
      repeats with one strand guanine rich. The protein portion of the complex is less
      well understood. The experiments presented in two recent papers represent
      different stages in the characterization of the telomeric DNA binding proteins.
      The first paper presents a structure-function study of the Oxytricha telomeric
      DNA binding proteins and the second paper shows the identification and initial
      characterization of a telomeric DNA binding activity from Xenopus laevis. These
      two reports provided valuable information in understanding the structure and
      function of telomeres.

PMID- 8135770
TI  - Simplicity amidst complexity in transcriptional initiation.

PMID- 8135771
TI  - Polyamines, chromatin structure and transcription.
AB  - Nucleosomes are the basic elements of chromatin structure. Polyamines, such as
      spermine and spermidine, are small ubiquitous molecules absolutely required for
      cell growth. Photoaffinity polyamines bind to specific locations in nucleosomes
      and can change the helical twist of DNA in nucleosomes. Acetylation of polyamines
      reduces their affinity for DNA and nucleosomes, thus the helical twist of DNA in
      nucleosomes could be regulated by cells through acetylation. I suggest that
      histone and polyamine acetylation act synergistically to modulate chromatin
      structure. On naked DNA, the photoaffinity spermine bound preferentially to a
      specific 'TATA' sequence element, suggesting that polyamines may be involved in
      the unusual chromatin structure in this region. Further work is needed to test
      whether the specificities shown by photoaffinity polyamines are also shown by
      cellular polyamines; such experiments are now feasible.

PMID- 8135772
TI  - Regulation of alternative splicing of the fibronectin IIICS domain by cytokines.
AB  - The primary fibronectin gene transcript is alternatively spliced in three
      regions, designated EIIIA, EIIIB and IIICS. While the functions of the EIIIA and
      EIIIB domains are still to be established, either end of the IIICS domain
      contains the cell-binding sites CS1 and CS5 recognised by the integrin VLA-4
      which is present on mononuclear cells. We have determined the effects of three
      cytokines upon fibronectin mRNA and IIICS splice variants in four cultured human
      cell lines using Northern hybridisation and PCR. In the cell line CAKI-2,
      interleukin 1 beta, Platelet-derived growth factor BB and transforming growth
      factor beta 1 all increased mRNA splice variants where the CS1 and CS5 regions
      were removed. This cytokine-induced change would lead to a decrease in the CS1
      and CS5 cell binding sites within the extracellular matrix. All the changes in
      spliceosome function increase use of downstream 3' splice acceptor sites and may
      represent use of a single common pathway by three different cytokines.

PMID- 8135773
TI  - Alteration in expression of MUC2 and MUC3 mRNA levels in HT29 colonic carcinoma
      cells.
AB  - The cDNAs for two mucins, MUC2 and MUC3, have been derived from intestinal cells,
      however, the mechanisms that control expression of these genes are unknown.
      Steady-state mRNA levels for mucin gene products were examined in HT29 colonic
      carcinoma cells. Cells were grown in a conventional glucose medium and a glucose
      free galactose medium to induce phenotypic differentiation. Northern blot
      analyses using cDNA probes of MUC2 and MUC3 were performed. MUC2 mRNA levels were
      decreased in cells grown in galactose medium compared to glucose medium whereas
      MUC3 mRNA levels were increased when cells were grown in galactose medium
      compared to those grown in galactose-free, glucose medium. This report shows
      steady state mucin gene expression is altered in HT29 cells grown in a medium
      that induces phenotypic differentiation and may provide a model for evaluation of
      induction of mucin gene expression.

PMID- 8135774
TI  - Regulation of undulin synthesis and gene expression in human fat-storing cells by
      acetaldehyde and transforming growth factor-beta 1: comparison with fibronectin.
AB  - Undulin and fibronectin (FN) are large extracellular matrix (ECM) glycoproteins
      possibly involved in cell-matrix interactions. In this study we analyzed the
      effect of acetaldehyde and transforming growth factor-beta 1 (TGF-beta 1) on
      undulin and FN synthesis in cultured fat-storing cells (FSC) isolated from wedge
      sections of normal human livers. Cultured human FSC expressed two mRNA
      transcripts (6.5 and 8.5 kb) specific for undulin. Acetaldehyde inhibited both
      undulin mRNA and protein expression, whereas it had an opposite (stimulatory)
      effect on FN synthesis. TGF-beta 1 induced a dose-dependent increase of both
      undulin and FN synthesis in FSC cultures. Furthermore, TGF-beta 1 antagonized the
      inhibitory effect of acetaldehyde on undulin production and potentiated the
      stimulatory effect of acetaldehyde on FN synthesis. Since undulin is involved in
      the supramolecular organization of fibrillar collagens and in their enzymatic
      degradation, its acetaldehyde-induced inhibition may contribute to ECM
      rearrangement in the early stages of alcoholic liver fibrosis.

PMID- 8135775
TI  - Induction of thyrotropin receptor (TSH-R) autoantibodies and thyroiditis in mice
      immunised with the recombinant TSH-R.
AB  - Two groups of 10 Balbc by Jico male mice were immunised on days 0, 15 and 35,
      with the extra cellular domain (ECD) of the human thyrotropin receptor (TSH-R)
      expressed as a fusion protein in bacteria (group 1) or with the maltose binding
      protein (MBP) fusion partner alone (group 2). Blood was obtained on days 0, 22,
      32, 42 and 49 and samples from the individual animals pooled for each group.
      Serum and immunoglobulin (IgG) preparations were tested, using CHO cells
      expressing the human TSH-R (JP26 and JP09) for thyroid stimulating (TSAb);
      thyroid blocking (TBAb) and thyrotropin binding inhibiting (TBII) activities.
      Neither serum nor IgGs were found to contain TSAb at any time point. TBII
      activity was present in the serum of both groups on day 32 and in group 1 only on
      day 49; when the test was performed on IgGs, only the MBP-ECD day 49 preparation
      remained significantly positive for TBII (p < 0.005). Significant TBAb activity
      was present in both the serum and IgG of group 1 day 49 (p < 0.005) and to a
      lesser extent on 42 (p < 0.02). Following the second immunisation (day 15) both
      groups and had decreased circulating T4 levels (p < 0.05) when compared with day
      0 in each case. Group 2 were unaffected by the third immunisation on day 35 but
      the MBP-ECD group again had significantly decreased T4 levels (p < 0.02) compared
      with MBP day 49 and (p < 0.03) when compared with MBP-ECD day 0. Histological
      examination of thyroids from group 1 animals revealed extensive vascularisation
      and an atypical lymphoblastoid infiltration which was not observed in control
      mice. These preliminary results indicate that care is required in interpreting
      data since a non-receptor antigen was shown to decrease circulating thyroxine and
      serum from these animals had apparent TBII like activity. However, the results
      obtained with the IgGs suggest that receptor autoantibodies can be induced by
      immunising with the human TSH-R, in addition, the immunised mice show
      histological evidence for the development of thyroiditis.

PMID- 8135776
TI  - Processing of interleukin-1 beta in synovial cells freshly isolated from patients
      with rheumatoid arthritis.
AB  - This study examined interleukin-1 beta (IL-1 beta) production by synovial cells
      from patients with rheumatoid arthritis (RA). Freshly isolated, plastic-adherent,
      synovial cells from ten of thirteen patients with RA secreted significant levels
      of IL-1 bioactivity, and the cells from five patients secreted more IL-1 beta
      bioactivity than IL-1 alpha bioactivity. Further, there was a relatively good
      correlation between IL-1 beta bioactivity and IL-1 beta converting enzyme (ICE)
      activity, suggesting that bioactive IL-1 beta is possibly generated through the
      action of ICE. Analysis of metabolically-labeled IL-1 by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), however, indicated that, although
      these cells contained both pre IL-1 alpha and beta intracellularly, they secreted
      predominantly pre IL-1 beta.

PMID- 8135777
TI  - Phosphorylation of nm23/nucleoside diphosphate kinase by casein kinase 2 in
      vitro.
AB  - We have investigated phosphorylation of human nucleoside diphosphate kinase
      (NDPK) and of homologous NDPK from different species by human casein kinase 2 (CK
      2). The human NDPK isotypes A and B were phosphorylated by CK-2 in vitro both
      when the purified proteins and total lysate of HL-60 leukemia cells were used.
      The homologous NDPK's from Yeast and E. coli were also substrates for CK-2 in
      vitro, but not Drosophila NDPK. Phosphorylation of all NDPK types by the CK-2
      holoenzyme was entirely polyamine-dependent. The CK-2 phosphorylation site in
      human NDPK A, that was about 2.5 times stronger phosphorylated than was the B
      isotype, was tentatively assigned to Ser-122. The location of the corresponding
      residue in the 3D-structure of the 80% homologous Drosophila NDPK suggests that
      its phosphorylation may directly influence substrate binding and/or catalysis.

PMID- 8135778
TI  - Identification of a TGF-beta responsive element in the human elastin promoter.
AB  - In a previous report (Marigo, V., Volpin, D., and Bressan, G. M. (1993) Biochim.
      Biophys. Acta 1172, 31-36) it was shown that the elastin promoter contains a
      region mediating transcriptional activation by TGF-beta in aorta cells, but not
      in tendon fibroblasts from chick embryos. In this paper we have identified the
      sequence responsible for this effect by a combination of CAT assays with mutant
      constructs, DNase I footprinting and electrophoretic mobility shift assays. This
      TGF-beta responsive element binds different nuclear proteins in chick embryo
      aorta and tendon cells. Whereas association of the aorta protein(s) to the
      element is necessary for TGF-beta activation, binding of the tendon protein(s)
      has apparently no effect on promoter stimulation by the cytokine.

PMID- 8135779
TI  - Single-molecule analysis of the actomyosin motor using nano-manipulation.
AB  - The elementary events in energy transduction by the actomyosin motor, driven by
      ATP hydrolysis, were directly recorded from multiple and single molecules using a
      recently developed technique for nano-manipulation of single actin filaments by a
      microneedle. In order to avoid the effects of random orientation of myosin and
      association of myosin with an artificial substrate in the surface motility assay,
      we used single myosin-rod cofilaments with various ratios. Distinct actomyosin
      attachment, force generation (the power stroke) and detachment events were
      detected at a very low myosin: rod ratio. At high load, one power stroke
      generated 5-6 pN peak force and 2.3 pN force averaged over the cycle, which were
      compatible with those deduced from noise analysis of force fluctuations caused by
      multiple molecules. As the load was reduced, the length of the power stroke
      increased. At near zero load, the length of a power stroke was approximately 17
      nm. The results suggested that an ATPase cycle produces one power stroke at high
      load and many ones at low load.

PMID- 8135780
TI  - Calcineurin activates transcription from the GM-CSF promoter in synergy with
      either protein kinase C or NF-kappa B/AP-1 in T cells.
AB  - Two cis-acting elements GM-kappa B/GC-box and CLE0, of the granulocyte-macrophage
      colony-stimulating factor (GM-CSF) gene are required for maximal induction in
      Jurkat T cells by costimulation with phorbol-12-myristate acetate (PMA) and Ca2+
      ionophore (A23187). The GM-kappa B sequence is recognized by NF-kappa B, which is
      mainly induced by PMA. The CLE0 sequence interacts with factors, related to a PMA
      induced AP-1 and a PMA/A23187-induced NF-AT. We examined whether signal
      transducing components in T cells can activate transcription of the GM-CSF gene.
      Cotransfection of NF-kappa B (p50/p65)- or AP-1 (c-Jun/c-Fos)-expression vectors
      into Jurkat cells with a luciferase reporter containing the GM-CSF promoter did
      not stimulate transcription from the GM-CSF promoter. In contrast, cotransfection
      with a combination of NF-kappa B and AP-1 significantly augmented transcription
      from the GM-CSF promoter containing the GM-kappa B/GC-box and the CLE0 (AP-1/NF
      AT). Expression of a constitutively active calcineurin (CN), a Ca2+/calmodulin
      dependent protein phosphatase, potentiated by two fold the transcriptional
      activation by NF-kappa B/AP-1. Both constitutively active forms of CN and protein
      kinase C (PKC) synergistically activated transcription from the GM-CSF promoter.
      These results suggest that cooperation among NF-kappa B-, AP-1- and NF-AT-binding
      sequences is required for induction of the GM-CSF gene through PKC- and Ca2+
      signaling pathways downstream of T cell activation.

PMID- 8135781
TI  - SS33410, an inhibitor for inflammation, blocks the intracellular transport of VSV
      G glycoprotein in BHK cells.
AB  - We have studied the effect of SS33410, an inhibitor for inflammation, on the
      intracellular transport and processing of the vesicular stomatitis virus (VSV) G
      glycoprotein as a model integral membrane protein. Delivery of G glycoprotein to
      the cell surface was blocked by 0.5 microgram/ml of SS33410 without any
      significant inhibition of protein synthesis. The G glycoprotein accumulated
      intracellularly electrophoresed a little faster than the control mature one
      excreted to the medium. The affinity for concanavalin A-agarose (Con-A) column
      suggested that most of the G glycoprotein oligosaccharides were of the high
      mannose type. These results indicate that processing of N-glycosidic
      oligosaccharide is incomplete, suggesting that intracellular trafficking is
      arrested before reaching to the trans Golgi compartments in the presence of
      SS33410.

PMID- 8135782
TI  - Asymmetrical lipid charge changes the subconducting state of the potassium
      channel from sarcoplasmic reticulum.
AB  - The K+ channel of sarcoplasmic reticulum was incorporated into planar lipid
      bilayers having various net surface charges. The conductance of both the main
      state and substate increased with the increase in negative charges of the
      membrane and vice versa. The change in the conductance of the substate was larger
      than that of the main-state. The K+ channel reconstituted into asymmetrical
      planar lipid bilayers revealed that the effect on the substate was derived from
      only one half (trans) of the bilayer. The substate of the K+ channel may assume a
      conformation in which part of the channel located at the trans side is
      susceptible to some changes induced by the trans surface charge.

PMID- 8135783
TI  - Complete 5' noncoding region is necessary for the efficient internal initiation
      of hepatitis C virus RNA.
AB  - The mechanism of translational initiation by the 5' noncoding region (5'NCR) of
      hepatitis C virus (HCV) genome was analyzed. Using an in vitro translation system
      with artificial RNA containing a modified 5' NCR of HCV under the various KCl
      conditions, nucleotides (nt.) 62 to 341 of the HCV 5'NCR were not functional as
      an internal ribosome entry site (IRES). However, the full-length 5'NCR (nt. 1 to
      341) produced an efficient internal initiation. To identify the essential region
      of the HCV-IRES, various mutants were produced in which stem-loops, predicted by
      secondary structure analysis of the HCV 5'NCR, were deleted. These constructs
      were analyzed by in vitro translation. Comparison of translation efficiency among
      these mutants suggested that the alpha- or both alpha- and beta-branches of
      domain II are essential for efficient translation. Moreover, the formation of
      correct secondary structure of IRES seems to be stabilized by the presence of
      domain I in 5'NCR. Furthermore, the uncapped 5'NCR of HCV promotes translation
      more efficiently than capped truncated 5'NCR constructs. Our results strongly
      suggested that complete 5'NCR containing all stem-loop structures is necessary
      for initiation by HCV-IRES.

PMID- 8135784
TI  - Characterization of NF(P), the nuclear factor that interacts with the regulatory
      P sequence (5'-CGAAAATTTCC-3') of the human interleukin-4 gene: relationship to
      NF-kappa B and NF-AT.
AB  - The P sequence of the human interleukin-4 (IL-4) gene, which was defined as a
      responsive element for phorbol 12-myristate 13-acetate and calcium ionophore
      (A23187) in Jurkat T cells, shares sequence similarity with the NF-kappa B and
      the NF-AT binding sites. We examined whether NF(P), a nuclear factor specific for
      the P sequence, is related to NF-kappa B and NF-AT. NF-kappa B (P65 or P65/P50
      heterodimer) bound to the P sequence in electrophoretic mobility shift assays
      (EMSA) and activated transcription through the P sequence when expression
      plasmids were cotransfected with P sequence-driven reporter plasmids in Jurkat T
      cells. In EMSAs, NF(P) binding was inhibited by the unlabeled NF-AT binding site
      but not by the unlabeled AP1 binding site and purified NF-AT contained an
      activity that bound to the P sequence. Both mobility shift and sequence
      specificity of NF-AT were similar to those of NF(P) and only a small amount of
      P65 was detected in NF(P) in crude nuclear extracts. These results indicate that
      the component(s) of NF-AT has the potential to reconstitute NF(P) whereas NF
      kappa B alone cannot account for NF(P) in crude extracts. Unlike NF-AT, NF(P)
      does not contain AP1 as its DNA binding component.

PMID- 8135786
TI  - Enhancement of phorbol ester-induced production of tumor necrosis factor alpha by
      thalidomide.
AB  - The effect of thalidomide [racemic (DL-) form and optically pure (D- and L-)
      forms] on tumor necrosis factor (TNF) alpha production by human leukemia cell
      lines (HL-60, K562 and U937) stimulated with 12-O-tetradecanoylphorbol-13-acetate
      (TPA) was investigated. Though thalidomide has been regarded as a specific
      inhibitor of TNF-alpha production, our study indicated that all forms of
      thalidomide enhanced (but did not inhibit) the TPA-induced TNF-alpha production
      by the human leukemia cell lines investigated. The effects of thalidomide on TNF
      alpha production might be cell type-specific.

PMID- 8135785
TI  - Effects of nitric oxide on red blood cells: changes in erythrocyte resistance to
      hypotonic hemolysis and potassium efflux by experimental maneuvers that decrease
      nitric oxide.
AB  - To determine the role of nitric oxide (NO)-dependent mechanisms on erythrocyte
      properties, we exposed red cells to L-arginine competitive analogues, 8Br-cyclic
      guanosine monophosphate (8Br-cGMP) and neutrophil-eliminating filters. These
      treatments significantly decreased hypotonic hemolysis, increased potassium
      efflux and caused a spiculate change in erythrocyte morphology. These effects
      were related to a decrease of NO caused by the three types of treatments.

PMID- 8135787
TI  - Novel subtype of human angiotensin II type 1 receptor: cDNA cloning and
      expression.
AB  - Angiotensin II (AII) plays a major role in regulation of cardiovascular function
      and fluid homeostasis through the action of an AII type 1 receptor (AT1R). The
      cDNA encoding a novel subtype of human AT1R (AT1bR) was cloned from a human
      placental cDNA library. The full-length cDNA clone (1563 bp) encoded a
      polypeptide that consists of 359 amino acid (aa) residues with 97.2% aa identity
      to the human AT1aR. All the aa replacements between two human AT1Rs reside within
      the C-terminal half region of AT1R molecule. The 2.4-knt AT1bR mRNA is expressed
      in the lung, placenta and liver, and differs from AT1aR mRNA in its tissue
      distribution. The AT1bR expressed in COS-7 cells is pharmacologically distinct
      from the human AT1aR.

PMID- 8135788
TI  - Novel subtype of human angiotensin II type 1 receptor: analysis of signal
      transduction mechanism in transfected Chinese hamster ovary cells.
AB  - We examined the intracellular signal transduction of two subtypes of human
      angiotensin II type 1 receptor (AT1aR and AT1bR) by means of the stable
      expression of each receptor cDNA in Chinese hamster ovary cells. Both receptors
      showed a rapid stimulation of phosphatidylinositol hydrolysis, a transient
      increase of intracellular Ca2+ concentration and an inhibitory action on the
      forskolin-induced cyclic AMP formation. Interestingly, at high AII concentrations
      (> 1 microM), these AT1bR-mediated responses were inhibited, whereas the AT1aR
      mediated responses were not. Thus, the two AT1Rs are considered to be coupled to
      the same signal transduction cascades, but to be regulated differently on the
      post-translational level (presumably desensitization).

PMID- 8135789
TI  - Little or no expression of the cholecystokinin-A receptor gene in the pancreas of
      diabetic rats (Otsuka Long-Evans Tokushima Fatty = OLETF rats).
AB  - Expression of the CCK-A receptor gene in the pancreas and pancreatic exocrine
      function was examined in diabetic model rats (OLETF) at 5 wks of age. Little or
      no CCK-A receptor was detected in the pancreas of OLETF rats. Pancreatic exocrine
      function in response to exogenous CCK and to bile-pancreatic juice diversion
      (endogenous CCK) was impaired in conscious OLETF rats. The pancreatic insulin and
      protein contents of OLETF (Otsuka Long-Evans Tokushima Fatty) and control LETO
      (Long-Evans Tokushima Otsuka) rats were not significantly different. No
      histological abnormalities or expression of pancreatitis associated protein (PAP)
      mRNA was detected in the pancreas in either group. These results suggest that
      OLETF rats are a new experimental model for congenital deficiency of CCK-A
      receptor in the pancreas.

PMID- 8135790
TI  - Analysis of amino acid substitution during divergent evolution: the 400 by 400
      dipeptide substitution matrix.
AB  - Most formal methods for analyzing the divergent evolution of protein sequences
      assume a Markov model where position i in a polypeptide chain undergoes amino
      acid substitution independently from position i + 1. The large number of aligned
      homologous sequence pairs available from the exhaustive matching of the protein
      sequence database makes it possible to examine this assumption empirically. We
      have constructed a 400 by 400 matrix that reports empirical probabilities for the
      interconversion of all pairs of dipeptides in proteins undergoing divergent
      evolution. Comparison of these probabilities with those expected if substitution
      at adjacent positions in a protein sequence were independent reveals interesting
      patterns that arise through the breakdown of this assumption. Several of these
      are useful in extracting conformational information from patterns of conservation
      and variation in homologous protein sequences.

PMID- 8135791
TI  - Properties of the catalytic domain of CDC25, a Saccharomyces cerevisiae GDP/GTP
      exchange factor: comparison of its activity on full-length and C-terminal
      truncated RAS2 proteins.
AB  - Two C-terminal fragments (334 and 509 amino acid residues) of CDC25, a
      Saccharomyces cerevisiae GDP/GTP exchange factor, and the RAS2 protein were
      purified from E. coli, using the pGEX system. With this method it was possible to
      avoid in part the proteolytic phenomena that usually convert full-length RAS2
      (42kDa) into 37 and 30kDa forms. Of the two CDC25 fragments containing the
      conserved catalytic domain, only CDC25-509 could enhance the guanine nucleotide
      exchange on RAS2. Comparison of the activities of RAS2-42/37kDa and RAS2-30kDa
      showed that the C-terminal region (112 residues) influences neither the intrinsic
      GDP/GTP exchange nor its stimulation by CDC25-509. RAS2-42/37kDa was somewhat
      more effective in enhancing the adenylylcyclase activity of a yeast membrane
      reconstituted system. CDC25-509 displayed a higher specific activity than the
      catalytic domains of the two CDC25-like proteins: S. cerevisiae SDC25 and mouse
      CDC25Mm.

PMID- 8135792
TI  - Peripheral blood lymphocytes display reduced K+ channel activity in aged humans.
AB  - Steady-state parameters of whole-cell K+ current have been determined in human
      peripheral blood lymphocytes of young (20-50 y.) and elderly (> 90 y.) volunteers
      by patch-clamp. The magnitude and voltage dependence of the K+ conductance were
      similar in both lymphocyte populations. The midpoint of steady-state inactivation
      was -53.3 +/- 2.3 mV for lymphocyte population of young individuals and -65.0 +/-
      3.0 mV for that of elderly, showing a significant shift to hyperpolarized
      potentials. The peak of the steady-state open probability of the K+ channels was
      decreased and shifted to depolarized potentials by approx. 12.5 mV for
      lymphocytes of elderly donors. It is suggested that the observed differences in
      the K+ current parameters may be at least partly responsible for the impaired
      responsiveness of elderly lymphocytes to proliferative stimuli.

PMID- 8135793
TI  - Cell death protection by 3-aminobenzamide and other poly(ADP-ribose)polymerase
      inhibitors: different effects on human natural killer and lymphokine activated
      killer cell activities.
AB  - The death of target cells by cytotoxic effector cells is a relevant biological
      phenomenon, where cells are activated and a very quick apoptotic program occurs.
      In order to test the hypothesis that the nuclear enzyme poly(ADP
      ribose)polymerase (PADPRP) plays a role in such a process, a variety of PADPRP
      inhibitors such as 3-aminobenzamide, nicotinamide, 4-aminobenzamide and luminol
      were used. All of them were able to strongly inhibit K562 target cell killing by
      human effector natural killer cells (NK) in a 4hr 51Cr release assay. PADPRP
      inhibitors were much less effective in protecting target cells when lymphokine
      activated killer cells (LAK) were used as effectors. These substances were active
      only when both target and effector cells were mixed, being ineffective on target
      or effector cells alone. On the whole, these data indicate that PADPRP is
      involved in the death of target cells. Moreover, the different sensitivity of NK
      and LAK activities to PADPRP inhibitors suggests that the molecular mechanisms
      underlying these two types of cytotoxicity are at least partially different.

PMID- 8135794
TI  - Expression of the soluble lectin L-14 gene is induced by TSH in thyroid cells and
      suppressed by retinoic acid in transformed neural cells.
AB  - Expression of the soluble lectin L-14 is low in normal and very high in
      transformed thyroid cells. We show that L-14 gene expression is transiently
      induced upon thyrotropin stimulation of normal quiescent FRTL-5 rat thyroid
      cells. Permanent activation of L-14 gene expression is obtained in the same cells
      infected with a wild-type and a temperature sensitive mutant of Kirsten murine
      sarcoma virus, both at the permissive and non permissive temperature for
      transformation. We also find that L-14 mRNA is undetectable in rat brain but is
      abundant in rat oligodendrocytes precursors transformed by polyoma middle T
      oncogene. Retinoic acid treatment of these transformed cells leads to acquisition
      of a differentiated phenotype accompanied by a 30-fold decrease of L-14 mRNA
      levels. Removal of retinoic acid restores both the transformed undifferentiated
      phenotype and high L-14 expression. Taken together these results indicate that
      growth stimulation and induction of cell differentiation are accompanied by
      strong modulation of L-14 gene expression.

PMID- 8135795
TI  - Immunocytochemical detection of parathyroid hormone-related protein in vascular
      endothelial cells.
AB  - The expression of parathyroid hormone-related protein (PTHrP) in cultured
      endothelial cells derived from bovine carotid artery was immunocytochemically
      investigated. The cells showed positive immunoreactivity for PTHrP abundantly in
      cytoplasm. PTHrP-like immunoreactivity was found in all endothelial cells under
      investigation. Negative control prepared with non-immune rabbit serum or with the
      antiserum preabsorbed with PTHrP showed no significant staining, indicating the
      specificity for immunostaining. Addition of 10% fetal calf serum to serum
      deprived endothelial cells did not significantly increase PTHrP-like
      immunoreactivity. These results suggest that endothelial cells express PTHrP
      constitutively and PTHrP may act as a new class of endothelium-derived relaxing
      factor.

PMID- 8135796
TI  - Improvements to the differential display method for gene analysis.
AB  - Differential display requires two primers to identify discordantly expressed
      mRNAs. Anchored primers with at least one G residue were superior to those which
      had one C residue and those ending in A or T were the least efficient. Arbitrary
      primers with GC pairs at the 5'end were superior to primers with GC pairs at the
      3'end. We found that screening of amplified DNA-fixed membranes by a slot blot
      manifold and hybridization with DNA probes made from sample RNA rapidly re
      screened with DNA fragments for differential expression, requires less RNA and is
      faster than Northern analysis. Similarly, hybridization of DNA fragments to
      plasmid DNA fixed to membranes and direct PCR sequencing rapidly determine
      homology to common laboratory plasmids prior to any further manipulation. These
      modifications permit rapid isolation and characterization of DNA fragments
      identified by differential display.

PMID- 8135797
TI  - A new Italian case of lipoprotein lipase deficiency: a Leu365- > Val change
      resulting in loss of enzyme activity.
AB  - We describe a second Italian family with primary Lipoprotein Lipase deficiency. A
      new mutation in exon 8 causes a Leu365- > Val change resulting in severe mass
      reduction and loss of enzyme activity. We suggest that this change interferes
      with the correct folding and stability of the protein and impairs the assembly of
      the active homodimer. The procedures applied are useful to screen a large sample
      of population for genetic variants and allow the clear identification of
      asymptomatic heterozygous subjects at risk from atherosclerosis disease.

PMID- 8135798
TI  - Site-directed mutagenesis of two highly conserved residues near the active site
      of phosphofructo-1-kinase.
AB  - Mutations of either of two highly conserved residues near the active site of
      Escherichia coli phosphofructokinase, Ile-126 or Asn-128, produce no changes in
      the Km for ATP, relatively small changes in kcat, and a large increase in the Km
      for fructose 6-P, despite the fact that these residues are not directly involved
      in substrate binding. A computer graphics analysis of the three-dimensional
      structure suggests that the mutations effect the orientation of Arg-252, a
      residue important both for fructose 6-P binding and for catalysis.

PMID- 8135799
TI  - Modulation of 12-0-tetradecanoylphorbol-13-acetate-induced epidermal ornithine
      decarboxylase activity by calcium and verapamil in mouse.
AB  - Calcium has been suggested to be an intracellular second messenger for ornithine
      decarboxylase (ODC) induction caused by 12-O-tetradecanoylphorbol-13-acetate
      (TPA). In the present study, the effects of dietary calcium supplement and
      calcium and verapamil injections on TPA-induced ODC activity in skin was
      investigated in CD-1 and SENCAR mouse. Dietary calcium supplement did not
      influence ODC induction caused by TPA. However, calcium injections enhanced the
      TPA-induced ODC activity in CD-1 and SENCAR mouse skin. Verapamil injections
      resulted in a significant decrease in TPA-induced ODC activity in CD-1 and SENCAR
      mice. These results suggest that calcium and calcium antagonists may play a role
      in skin tumor promotion caused by TPA.

PMID- 8135800
TI  - Molecular cloning of rat mast cell protease 1 and development of specific probes
      for its gene transcript.
AB  - Rat mast cell protease of type 1 (RMCP1) is a specific marker of connective
      tissue mast cells selectively occurring in some tissues, e.g., the tongue. Its
      amino acid sequence is known (Le Trong et al., Biochem. 1987, 26, 6988-6994) but
      not the corresponding nucleotide sequence. Amplification of mRNAs from rat tongue
      was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) using
      oligonucleotide primers corresponding to the translated region of rat mast cell
      protease 2 (RMCP2) gene. The cDNA obtained was subcloned and sequenced, leading
      to an amino acid sequence which matched the known 227 amino acid sequence. In
      addition there was, however, two sequences of 11 amino acids at the N-terminus
      and 13 amino acids at the C-terminus. The amino acid identity was of 74% with
      RMCP2, and of 76%, 65% and 90% with the mouse proteases MMCP1, MMCP2 and MMCP4,
      respectively. Based on the sequence of RMCP1 or RMCP2 cDNAs, selective
      oligoprobes were designed and their specificity established by Northern blot
      analysis of mRNAs purified from tongue and jejunum, two tissues containing
      selectively type 1 and 2 protease, respectively. Single 1.2 and 1.0 kb
      transcripts were evidenced in tongue and jejunum, respectively. In addition, a RT
      PCR method was developed to amplify selectively each transcript which may serve
      as reliable markers in the analysis of mast cell heterogeneity, differentiation
      and function.

PMID- 8135801
TI  - Point mutations of the thyrotropin receptor determining structural requirements
      for its ability to bind thyrotropin and to stimulate adenylate cyclase activity.
AB  - The two cysteines C494 and C569, located in the first and second extracellular
      loop, respectively, of the thyrotropin (TSH) receptor, were mutated to serines to
      test the functional significance of the putative disulfide bond between these two
      cysteines. Single (C494S and C569S) and double (C494/569S) mutant receptors were
      generated, transiently expressed in COS cells, and compared with regard to the
      ability to bind ligand and to mediate stimulation of adenylate cyclase activity.
      The double mutant retained ligand binding capacity, in contrast to the single
      cysteine mutants that were essentially devoid of binding capacity. The ability of
      the mutated receptor variants to stimulate adenylate cyclase activity was lost or
      greatly reduced.

PMID- 8135802
TI  - Cloning and sequencing of cDNA coding for Cry j I, a major allergen of Japanese
      cedar pollen.
AB  - cDNA clones coding for Cry j I, a major allergen of the Japanese cedar
      (Cryptomeria japonica) pollen, have been isolated. Two of the clones were
      sequenced and found to code for a putative 21-residue signal peptide and a 353
      residue mature protein with a derived molecular weight of 38.5 KDa. Five possible
      N-linked glycosylation sites were found in the sequence. Comparison of the
      nucleotide sequences of the two clones revealed sixteen nucleotide differences
      and these led to five amino acid exchanges in the mature allergen, indicating
      that an isoform of the Cry j I molecule exists. The deduced amino acid sequence
      of the Cry j I shows 46-48% identities with those of the Amb a I family and Amb a
      II, the major allergens of short ragweed. These findings should facilitate study
      of the structure-function relationship between the allergen and the
      immunocompetent cells.

PMID- 8135803
TI  - Regions of the human neurokinin A receptor involved in the generation of second
      messengers and in receptor desensitization.
AB  - Deletion analysis was used to study sites of human Neurokinin A receptor (HNKAR)
      necessary for signal transduction in CHO cells. Deletion of 62 and 81 amino acids
      from the c-terminus of HNKAR forms mutant receptors HNKAR delta 62 and HNKAR
      delta 81, which bind neurokinin A with high affinity but are functionally
      different. Wild type HNKAR and HNKAR delta 62 are functionally active whereas
      HNKAR delta 81 is functionally inactive. In addition, HNKAR and HNKAR delta 62
      were both desensitized to the neurokinin A signal within 5 minutes. The data
      indicates: 1) an intact cytoplasmic tail of the HNKAR is not critical for signal
      transduction, but the n-terminal amino acids of the cytoplasmic tail are
      necessary for signaling and 2) the c-terminal 62 amino acids are not necessary
      for desensitization.

PMID- 8135804
TI  - Involvement of protein kinase C in the inhibition of nitric oxide production from
      murine microglial cells by glucocorticoid.
AB  - The effects of glucocorticoid on the production of nitric oxide (NO) by murine
      microglial cells were investigated. Stimulation of the cells with
      lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) after the
      treatment of recombinant interferon-gamma (rIFN-gamma) resulted in the increased
      accumulation of nitrite in the medium. Concomitant incubation of the cells with
      dexamethasone (DEX) markedly inhibited the production of NO in a dose dependent
      manner. DEX also suppressed both rIFN-gamma and rIFN-gamma plus LPS-induced
      activity of the enzyme protein kinase C (PKC), a putative regulator of NO
      synthesis, but had only a modest inhibitory effect on basal activity. In
      addition, the inhibitory effect of DEX on NO generation was mimicked by the
      treatment of PKC inhibitors such as staurosporine (STSN) and polymyxin B. Our
      findings show that glucocorticoids have the potential to modulate central nervous
      system (CNS) NO production via the inhibition of PKC activity particularly under
      the conditions of stimulated production of NO, such as inflammatory and
      demyelinating CNS disorders.

PMID- 8135805
TI  - Rat heart fatty acid-binding protein content is increased in experimental
      diabetes.
AB  - Cytoplasmic fatty acid-binding protein (FABP) was assayed immunochemically in
      hearts from rats with insulin-dependent (IDDM) or non-insulin-dependent diabetes
      mellitus (NIDDM). FABP contents were 34% higher in IDDM and 103% higher in NIDDM
      hearts than in respective age-matched controls. FABP levels returned to control
      values when islets of Langerhans were transplanted into diabetic IDDM animals. In
      the diabetic hearts the activity of fructose-6-phosphate kinase decreased (IDDM
      and NIDDM animals), while that of 3-hydroxyacyl-CoA dehydrogenase increased
      (NIDDM animals only). These data indicate that experimental diabetes induces a
      marked increase of the FABP content of rat heart and suggests that this protein
      is involved in the enhanced fatty acid utilization by the diabetic heart.

PMID- 8135806
TI  - Nuclear translocation of heat shock protein 72 in liver cells of halothane
      exposed rats.
AB  - Immunocytochemical studies have revealed that one of the major heat shock
      proteins, HSP72, is induced in livers of rats that have been pretreated with
      phenobarbital and then administered halothane in a hypoxic gas mixture of 10%
      oxygen. To determine the sub-cellular localization of HSP72 in the livers of
      these rats 24 hr after halothane administration, cytoplasmic and nuclear
      fractions were prepared and separated by PAGE electrophoresis. Western blotting
      with a mouse monoclonal anti-HSP70 IgG antibody, which recognizes both the
      constitutive (HSP73) and inducible (HSP72) forms, revealed that HSP72 was induced
      and translocated into the nucleus in only those rats exposed to halothane under
      hypoxia following phenobarbital pretreatment. Nuclear translocation of HSP72
      under the latter conditions was confirmed by immunocytochemical staining using
      gold-conjugated secondary antibodies followed by digital laser microscopy with
      Nomarski optics. Neither phenobarbital pretreatment alone nor phenobarbital plus
      hypoxia treatment induced HSP72. No alteration in amount of HSP73 was observed
      under any of these conditions.

PMID- 8135807
TI  - Insulin action on whole body glucose utilization and on muscle glucose
      transporter translocation in mice.
AB  - Murine models of insulin resistance and diabetes are versatile and have been used
      to investigate genetic and metabolic disorders. However, the principal assays to
      assess insulin action, i.e., the euglycemic-hyperinsulinemic clamp and
      subcellular distribution of glucose transporters, have not been implemented in
      this species. Here we describe procedures which allow these methods to be adapted
      to mice. When normal C57bl/6j mice were infused with graded doses of insulin (1,
      3, 10 or 30 mU/kg/min) during a euglycemic-hyerinsulinemic clamp, the glucose
      infusion rate necessary to maintain euglycemia increased in a dose-dependent
      manner (7.4 +/- 1.7, 13.1 +/- 3.6, 24.1 +/- 2.3 or 34.8 +/- 7.5 mg/kg/min),
      respectively. Hindlimb muscles were isolated and samples of 2-3 g were subjected
      to subcellular fractionation finalizing on 25%, 30% and 35% sucrose gradients.
      Fraction F25 (plasma membranes) was enriched in alpha 2 Na+/K(+)-ATPase and GLUT1
      glucose transporters, whereas fraction F35 (intracellular membranes) was enriched
      in Ca(2+)-ATPase and GLUT4 glucose transporters. Following insulin treatment,
      GLUT4 increased in F25 and decreased in F35. Insulin treatment had no effect on
      GLUT1 in F25. However, unlike in rat skeletal muscle, GLUT1 was detectable in F35
      and its content decreased in this fraction following insulin treatment. The
      results demonstrate that whole-body glucose utilization can be assessed in mice
      using euglycemic-hyperinsulinemic clamps and demonstrate how subcellular
      fractionation procedures can be applied to murine muscle. Murine muscle GLUT4
      translocates from an intracellular storage site to the plasma membrane in
      response to insulin.

PMID- 8135808
TI  - Whole blood and plasma concentrations of 4-hydroxy-2-nonenal in Watanabe
      heritable hyperlipidemic versus New Zealand White rabbits.
AB  - Both plasma and whole blood concentrations of 4-hydroxy-2-nonenal (4HNE) were
      significantly elevated in a population (n = 6) of 2 year old Watanabe heritable
      hyperlipidemic rabbits relative to a population (n = 6) of New Zealand White
      rabbits. The plasma concentrations were 74 +/- 10 nmol/L for the Watanabe group
      and 47 +/- 6 nmol/L for the New Zealand White group. The whole blood
      concentrations were 364 +/- 55 nmol/L for the Watanabe group and 188 +/- 64
      nmol/L for the New Zealand White group. These results indicate that 4HNE
      concentrations in blood can be elevated in individuals with atherosclerosis and
      demonstrate the potential link between the formation of 4HNE and the progression
      of atherosclerosis.

PMID- 8135809
TI  - Structure-function analysis of Bacillus anthracis edema factor by using
      monoclonal antibodies.
AB  - Edema toxin of Bacillus anthracis is composed of protective antigen (PA) and
      edema factor (EF), a calcium- and calmodulin-dependent adenylate cyclase. At
      least five different antigenic regions of EF were identified using a competitive
      binding, enzyme-linked immunosorbent assay of paired monoclonal antibodies
      (mAbs). Two mAbs, 9F5 and 7G10, inhibited the binding of 125I-EF to cell-bound
      PA. However, only 9F5 inhibited the elongation response of Chinese hamster ovary
      cells in the presence of edema toxin. Cleavage of EF at the two aspartic acid
      proline residues by acid hydrolysis resulted in three fragments: a C-terminal 17
      kDa fragment, a central 53 kDa fragment, and an N-terminal 18 kDa fragment.
      Immunoblots of EF cleaved by formic acid mapped mAbs 9F5 and 7G10 to the N
      terminal 18 kDa fragment, mAb 1E6 to the C-terminal 17 kDa fragment, and the
      remaining 7 mAbs to the central 53 kDa fragment. mAbs 7G10 and 9F5 defined an
      antigenic region within amino acids 1-156 of EF which is involved in interaction
      with PA in forming edema toxin.

PMID- 8135810
TI  - The inhibition of sugar-induced structural alterations in collagen by aspirin and
      other compounds.
AB  - With age human collagen demonstrates, amongst other changes, reductions in
      solubility, elasticity and permeability. Many of these changes have been
      attributed to non-enzymic glycosylation (glycation)-a spontaneous addition of
      sugar molecules to any protein with free amino groups. The resulting formation
      and accumulation of Advanced Glycation End-products, some of which may be cross
      links, has been shown in both long- and short-lived proteins. We have shown that
      glycation of human corneal and scleral collagen increases with age and that this
      is accompanied by increases in cross-linking and collagen intermolecular spacing.
      We have now investigated several compounds that have been used to inhibit
      glycation, including aspirin, and have shown that all the inhibitors also prevent
      the increase in intermolecular spacing caused by glycation.

PMID- 8135811
TI  - cDNA sequences encoding human fructose 1,6-bisphosphatase from monocytes, liver
      and kidney: application of monocytes to molecular analysis of human fructose 1,6
      bisphosphatase deficiency.
AB  - Fructose 1,6-bisphosphatase deficiency is an autosomal recessive inherited
      disorder of gluconeogenesis. We could isolate cDNAs encoding human fructose 1,6
      bisphosphatase from normal monocytes, liver and kidney, but not from normal
      lymphocytes. The cDNAs contained an open reading frame coding for 338 amino
      acids, and their nucleotide sequences in monocytes and liver were identical.
      G644C645 nucleotides in this sequence were the same as those of cDNA from HL-60
      cells, although our result differed from a previous report (M. El-Maghrabi et al.
      (1993) J. Biol. Chem. 268, 9466-9472) on an alteration to C644G645 nucleotides in
      human liver cDNA resulting in a change of Gly-214 to Ala-214 in the enzyme. The
      Gly-214 (GGC) residue was therefore conserved in the enzymes hitherto isolated
      from humans and other animals. Analysis of monocytes in seven patients with
      fructose 1,6-bisphosphatase deficiency showed a DNA fragment with apparent normal
      size in two sisters but no detectable DNA fragment in the other five patients.
      Monocytes were thus useful as an alternative source for mRNA from human liver for
      the molecular analysis of fructose 1,6-bisphosphatase deficiency.

PMID- 8135812
TI  - On the analysis of bovine trypsin by electrospray-mass spectrometry.
AB  - In this paper the results obtained from an electrospray mass spectrometric (ES
      MS) analytical study of commercial grade bovine trypsin are presented and
      discussed. It is proven, somewhat contrary to an earlier report, that ES-MS
      analysis may be performed routinely on a triple quadrupole mass spectrometer
      using the normal ES-MS raw data transformation procedures to identify and
      quantify the three forms of trypsin, namely, beta, alpha and psi, present in the
      samples. Further, it was found that all of the samples analysed contained small
      amounts of two peptides of M(r) = 5447 and 17,882 Da, which are postulated to
      originate from catalytic cleavage of alpha-trypsin by beta-trypsin.

PMID- 8135813
TI  - A novel heparin-binding protein, HBp15, is identified as mammalian ribosomal
      protein L22.
AB  - A 15kDa-protein (HBp15) was purified from mouse submandibular gland and bovine
      brain by virtue of its heparin-binding property. The amino acid sequences of
      mouse and bovine HBp15 showed a high degree of homology to a sea urchin protein
      encoded by gene called "development specific protein 217." Using reverse
      transcription-polymerase chain reaction methods, cDNA clones for HBp15 were
      isolated from submandibular gland mRNA of mouse, human and pig, and sequenced.
      Database search of HBp15 showed that HBp15 also resembles yeast ribosomal protein
      YL31 in addition to the 217 protein. Using specific antibodies against HBp15,
      HBp15 was identified as mammalian ribosomal protein L22, for which no sequence
      information is available.

PMID- 8135814
TI  - Effect of isoquinolinesulfonamides on heat shock gene expression during heating
      at 41 degrees C in human carcinoma cell lines.
AB  - The possible involvement of PKC in the regulation of heat shock genes expression
      was investigated with three isoquinolinesulfonamide derivatives (H-7, H-8, and
      HA1004) in DUT-145, MCF-7, and MCF-7/ADR cells. The drug was added 1 hr before
      and during heating at 41 degrees C. Northern blots show that the levels of HSP70
      and HSP28 mRNA increased rapidly and reached maximal values within 4-8 hr and 8
      12 hr, respectively. H-7 and H-8 which are potent PKC inhibitors selectively
      suppressed the accumulation of HSP70 mRNA as well as the synthesis of HSP70. In
      contrast, HA1004 which is a potent PKA inhibitor but a weak PKC inhibitor did not
      affect HSP70 gene expression. These results suggest that PKC rather than PKA
      plays an important role in the regulation of heat shock gene expression.

PMID- 8135815
TI  - Run-down of calcium current is related to intracellular sodium.
AB  - Run-down of Ca2+ current was studied in isolated guinea pig ventricular cells and
      it was found to be attenuated by intracellular sodium. Calcium currents were
      recorded after activation of Na+ channels by a step pulse. The "run-down" in 30
      min was significantly reduced compared with control cells. When NaCl (0.1-10 mM)
      diffused from the micropipette into the cells, run-down of Ca2+ current was also
      significantly attenuated. However, the resulted increase of intracellular Na+ did
      not affect voltage dependent activation of Ca2+ current, but the duration of the
      action potential was shortened slightly.

PMID- 8135816
TI  - Inherited enhancement of hydroxyl radical generation and lipid peroxidation in
      the S strain rats results in DNA rearrangements, degenerative diseases, and
      premature aging.
AB  - Previously by selection and inbreeding of Wistar rats susceptible or resistant to
      the cataractogenic effect of galactose the S and R rat strains differing in the
      intensity of hexose transport into the animal cells were developed. High level of
      OH-radical generation and enhanced lipid peroxidation are revealed in the liver
      and myocardium of the S rats in contrast to the R rats. Data are obtained
      supporting the view that enhanced generation of OH-radicals within the S rat
      tissues is due to oxidation and autooxidation of the abundant amounts of
      monosacharides intensely accumulating in the rat cells. In spite of continuous
      inbreeding for more than 40 generations and a high rate of homozygosity, numerous
      DNA rearrangements are revealed in the S rat genomes. Fragility of the S rat cell
      membranes is detected. Cataracts and other lens lesions, emphysema, tumors,
      cardiomyopathy-like changes in the myocardium, scoliosis, brain disfunctions are
      characteristic of the S rats, as well as low fertility and short life-span
      indicative of premature aging.

PMID- 8135817
TI  - GR transcripts are localized during early Xenopus laevis embryogenesis and
      overexpression of GR inhibits differentiation after dexamethasone treatment.
AB  - We have studied the spatial expression of the Xenopus GR in early embryos by
      whole-mount in situ hybridization. At the gastrula stage, GR mRNA is localized in
      the dorsal ectoderm. By the early neurula stage, GR transcripts were detected
      along the notoplate. Between mid and late neurula stages, GR mRNA was not
      detectable. At the tailbud stage, GR mRNA was found in the anterior part of the
      embryo, including the cement gland, eyes, brain, the foregut, stomodeal
      hypophyseal anlage, the olfactory placodes, head mesenchyme and somites.
      Injection of Xenopus GR RNA into zygotes followed by treatment dexamethasone from
      the blastula stage onwards inhibits early differentiation. Expression of Xbra,
      gsc and histone H3 genes in these embryos is not inhibited, indicating that the
      GR effects are not due to a general squelching effect on transcription.

PMID- 8135818
TI  - Modulation of the osteoclast Ca2+ receptor by extracellular protons: possible
      linkage between Ca2+ sensing and extracellular acidification.
AB  - We report a sensitivity of the osteoclast cell surface Ca2+ receptor to
      extracellular protons. Freshly isolated rat osteoclasts were exposed to the known
      agonists of the Ca2+ receptor, Ca2+ and Ni2+, in extracellular solutions set at
      different pH values. Decreasing the extracellular pH from 7.8 to 4.0 units
      markedly potentiated the cytosolic Ca2+ signals elicited in response to Ca2+
      receptor activation by either Ni2+ (50 microM, 500 microM or 5 mM) or Ca2+ (5
      mM). Each response consisted of a rapid and usually transient elevation of
      cytosolic [Ca2+]. Maximal cytosolic [Ca2+] responses were obtained at pH values
      of 6.6 (for 5 mM-[Ni2+]) and 4.0 units (for 5 mM-[Ca2+]). Finally, the effects of
      extracellular pH persisted in Ca(2+)-free, EGTA-containing solutions, suggesting
      a modulation of intracellular Ca2+ release.

PMID- 8135819
TI  - A novel human homologue of a dead-box RNA helicase family.
AB  - Putative cDNA clones for a nuclear antigen that cross-reacts with anti-human
      aldolase A monoclonal antibody MAb1A2 were isolated from the HeLa lambda gt11
      cDNA library and a candidate clone (clone 3) was analyzed. The cDNA has an open
      reading frame (ORF) of 1,317 bp encoding a novel RNA helicase belonging to the
      DEAD RNA helicase family. The ORF also contains a nuclear targeting signal and
      the epitope for MAb1A2. The putative RNA helicase has sequence similarity to
      Escherichia coli RNA helicase DEAD, mouse translation factor eIF-4A, and human
      p68 and p54.

PMID- 8135820
TI  - Aminoethylcysteine ketimine decarboxylated dimer inhibits mitochondrial
      respiration by impairing electron transport at complex I level.
AB  - The product of the spontaneous dimerization and decarboxylation of
      aminoethylcysteine ketimine (simply named the dimer in this note) has been
      investigated for a possible biochemical activity. It has been found that the
      dimer inhibits the ADP-dependent oxidation of NAD(+)-linked substrates in rat
      liver mitochondria and electron transport from NADH to O2 in bovine heart
      submitochondrial particles (SMP). Oxidation of succinate by SMP is not impaired
      by concentrations of the dimer inhibiting almost totally NADH oxidation.
      Furthermore, the dimer did not affect the rotenone-insensitive electron transfer
      from NADH to menadione. These results give a preliminary indication suggesting
      that the dimer inhibits electron flow from NADH dehydrogenase to ubiquinone at or
      near the rotenone binding site(s). The dimer inhibition falls in the same range
      exhibited by some neurotoxins which are known to interact with the rotenone
      binding site.

PMID- 8135821
TI  - Crystallization of monodisperse maltoporin from wild-type and mutant strains of
      various Enterobacteriaceae.
AB  - Maltoporin has been purified by affinity chromatography on starch gel columns.
      This single-step procedure affords the rapid purification of active protein from
      wild-type and mutants of E. coli, and from other Gram-negative bacteria. The
      monodisperse protein was crystallized under various conditions. Several
      preparations have yielded crystals amendable to X-ray analysis, notably a single
      cysteine substitution, S57C.

PMID- 8135822
TI  - Identification of mouse mammary fibroblast-derived mammary growth factor as
      hepatocyte growth factor.
AB  - A growth factor for normal and neoplastic mouse mammary epithelial cells in
      primary culture was partially purified from the conditioned medium (CM) of mouse
      mammary fibroblasts. The N-terminal amino acid sequence of the major 33 kD
      protein separated on SDS-polyacrylamide gel electrophoresis under reducing
      conditions suggested that the growth factor is closely related to hepatocyte
      growth factor (HGF). To examine whether mammary growth factor is identical to HGF
      we cloned mouse HGF cDNA from mammary fibroblasts using PCR with primers designed
      from the previously reported human and rat HGF cDNA sequences. We then expressed
      the cloned mouse HGF cDNA in COS-1 cells. The CM from mouse HGF cDNA-transfected
      COS-1 cells stimulated the growth of mammary tumor cells in a manner similar to
      the CM from mammary fibroblasts. From these observations it is concluded that
      mammary growth factor produced by mammary fibroblasts is identical to mouse HGF.

PMID- 8135823
TI  - Insulin receptor kinase phosphorylates protein tyrosine phosphatase containing
      Src homology 2 regions and modulates its PTPase activity in vitro.
AB  - To clarify the role of protein tyrosine phosphatase (PTPase) containing a pair of
      Src homology 2 (SH2) regions upon insulin signaling, we studied the interactions
      between the insulin receptor and SH-PTP2 coupled to glutathione-S-transferase. A
      full length SH-PTP2 was phosphorylated by insulin receptor kinase and associated
      with the insulin receptor in vitro. The N-terminal SH2 domain was more
      phosphorylated than the other SH2 domain of SH-PTP2. However, both SH2 domains of
      SH-PTP2 were necessary for association with insulin receptors. Phosphorylation of
      the SH2 domains of SH-PTP2 resulted in decreased PTPase activities toward the
      phosphorylated insulin receptor. These results indicate that the insulin receptor
      can negatively regulate SH-PTP2 activity by means of phosphorylating the SH2
      domains.

PMID- 8135824
TI  - Bundling of actin filaments by myosin light chain kinase from smooth muscle.
AB  - Myosin light chain kinase has an inhibitory effect on the interaction of actin
      filaments with phosphorylated smooth muscle myosin. Myosin light chain kinase
      binds to actin filaments, and the inhibition is attributable to the actin-binding
      activity and not the kinase activity of myosin light chain kinase [Kohama et al.
      (1992) Biochem. Biophys. Res. Commun. 184, 1204-1211]. We now report that myosin
      light chain kinase is able to assemble actin filaments into thick bundles, which
      can be visualized by optical and electron microscopy and can be monitored by
      measuring the sedimentation and flow birefringence of actin filaments. The
      bundling activity of myosin light chain kinase is abolished by calmodulin in the
      presence of Ca2+. The possibility is discussed that myosin light chain kinase has
      multiple actin-binding sites through which it can cross-link actin filaments.

PMID- 8135825
TI  - Potent activation of phospholipase D by phenylarsine oxide in rat basophilic
      leukemia (RBL-2H3) cells.
AB  - A putative protein tyrosine phosphatase inhibitor, phenylarsine oxide (PAO),
      potentiated phospholipase D (PLD) activity concentration-dependently in [3H]
      oleic acid-labeled rat basophilic leukemia (RBL-2H3) cells without significant
      increase in phosphatidylinositol-specific phospholipase C (PI-PLC) activity.
      Although PAO induced tyrosine phosphorylation of several proteins, both PAO
      induced PLD activation and tyrosine phosphorylation were not affected by a
      protein tyrosine kinase inhibitor, genistein. Another tyrosine kinase inhibitor,
      herbimycin A, prevented the PAO-induced PLD stimulation but had no effect on
      protein tyrosine phosphorylation. However, depletion of protein kinase C (PKC)
      greatly reduced PAO-stimulated PLD activity. These results indicate that PKC but
      not tyrosine kinase may be involved in PAO-mediated PLD activation.

PMID- 8135826
TI  - Effect of myosin light chain kinase inhibitor wortmannin on the wound repair of
      cultured gastric mucosal cells.
AB  - The effects of myosin light chain kinase inhibitor wortmannin on wound
      restoration were investigated using a culture cell model. Rabbit gastric mucosal
      cells formed confluent monolayer cell sheets within 48h. Cell sheets were wounded
      to create wounds of uniform size. The restoration was monitored by a time-lapse
      video disc recorder and was analyzed. The wound was completely restored with
      early cell migration and late proliferation in controls. Wortmannin inhibited
      cell migration, thus inhibiting proliferation. Results indicate that the
      cytoskeleton plays a key role in the restoration of gastric mucosa.

PMID- 8135827
TI  - Induction of apoptotic cell death in differentiating neuroblastoma SH-SY5Y cells
      by colchicine.
AB  - In retinoic acid (RA)-differentiated SH-SY5Y cell cultures, colchicine could
      induce cell death, accompanied by the typical ladder pattern of DNA fragmentation
      found in apoptotic cells. This effect could be attenuated by the protein
      synthesis inhibitor cycloheximide. The protein kinase inhibitor H-89 efficiently
      reduced colchicine-induced cell death. These results suggest that the mechanism
      for colchicine-induced cell death may act, at least in part, through the
      activation of apoptosis in differentiating SH-SY5Y cells.

PMID- 8135828
TI  - Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta
      oxidation trifunctional protein.
AB  - Trifunctional protein deficiency, a typical mitochondrial long-chain fatty acid
      beta-oxidation defect, is caused by the abnormality of mitochondrial long-chain
      enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase
      trifunctional protein consisting of four moles of alpha-subunit and four moles of
      beta-subunit. We cloned, sequenced, and expressed the following cDNAs for the
      alpha- and beta-subunits of human trifunctional protein. The 2,690-bp cDNA clone
      had a 2,289-bp open reading frame encoding a 82,958-Da precursor and a 78,969-Da
      mature subunit (alpha-subunit). Expression of this cDNA in mammalian cells
      yielded a polypeptide with the long-chain enoyl-CoA hydratase and long-chain 3
      hydroxyacyl-CoA dehydrogenase activities. The 1,991-bp cDNA clone had a 1,422-bp
      open reading frame encoding a 51,293-Da precursor and a 47,484-Da mature subunit
      (beta-subunit). Expression of this cDNA in mammalian cells yielded a polypeptide
      with the long-chain 3-ketoacyl-CoA thiolase activity.

PMID- 8135829
TI  - The ligand-binding site of the estradiol receptor resides in a non-covalent
      complex of two consecutive peptides of 17 and 7 kDa.
AB  - A non-covalent complex of a 17 and a 7 kDa peptide was isolated from a Lys-C
      digest of the C-terminal 32 kDa half of the estradiol receptor by
      immunoadsorption. The 17 kDa part extends from K303 to K467, the 7 kDa part from
      S468 to K529 (or K531). The components are held together by hydrophobic
      interactions and can be separated by SDS/PAGE. They react on Western blots with
      MAB 13H2 (17 kDa) and MAB H222 (7 kDa), respectively. The native complex binds
      estradiol with high affinity and is recognized both by MAB 13H2 and H222,
      indicating that both peptides contribute to the ligand-binding niche.

PMID- 8135830
TI  - Two isoforms of the rat kidney EP3 receptor derived by alternative RNA splicing:
      intrarenal expression co-localization.
AB  - Two different clones, named rEP3A (approximately 2.2 kb) and rEP3B (approximately
      5.2 kb), were isolated from a rat kidney cDNA library by a homology screening
      approach. rEP3A was shown to encode the rat kidney prostaglandin E receptor EP3
      subtype (rEP3A receptor) (Takeuchi, K. et al. B.B.R.C. (1993) 194: 885). rEP3B
      receptor differs only in its carboxyl-terminal tail (Ile-336 to Pro-364) from
      rEP3A receptor. Southern blot analysis of genomic DNA has suggested that the EP3
      receptor gene is a single copy gene. RT-PCR using microdissected nephron segments
      showed co-expression of both receptor mRNAs specifically in distal nephron
      segments such as mTAL, cTAL, CCD and IMCD, whereas no significant expression of
      both receptor mRNAs was detected from GL, PCT, and PST. In conclusion, we have
      cloned an isoform of the rat kidney EP3 receptor, rEP3B receptor. rEP3A and rEP3B
      receptors are suggested to be derived by alternative RNA splicing, and both
      receptors are co-localized to distal tubules exerting an effect on water and
      electrolyte metabolism.

PMID- 8135831
TI  - A new human slow skeletal troponin T (TnTs) mRNA isoform derived from alternative
      splicing of a single gene.
AB  - A human muscle cDNA library was screened for slow skeletal troponin T (TnTs).
      Sequence analysis revealed that one of the selected clones had a cDNA coding
      sequence different from the two previously described. RNase protection assays
      confirmed the expression of this new isoform in adult skeletal muscle. In
      addition, results of the RNase protection assays strongly suggested the
      expression of a fourth isoform. These isoforms for human slow TnT most likely
      result from combinatorial alternative splicing of a single gene.

PMID- 8135832
TI  - Two isoforms of G protein-coupled receptor kinase 4 identified by molecular
      cloning.
AB  - Using PCR we found that G protein-coupled receptor kinase4 (GRK4) mRNA is
      expressed only in brain out of several tissues tested. In the brain two
      amplification products were generated. Sequence analysis revealed that the two
      fragments differed only by the presence or absence of an in-frame-sequence of 96
      bp/32 amino acids, located near the N-terminal of the kinase. This demonstrates
      the existence of two isoforms of GRK4 which were named GRK4A and GRK4B in the
      presence or absence of the insert, respectively. This is the first evidence that,
      within the GRKs gene family, different isoforms do exist.

PMID- 8135833
TI  - Chromosomal assignment of the human SA gene to 16p13.11 and demonstration of its
      expression in the kidney.
AB  - The SA gene is a novel gene of yet unknown function recently implicated in blood
      pressure regulation in rodent models of genetic hypertension. In this study we
      have located the human homologue of the SA gene to chromosome 16p13.11, by a
      combination of fluorescence in-situ hybridization and analysis of somatic cell
      hybrids carrying different segments of chromosome 16. This should facilitate
      investigation of its role in the genetic tendency to hypertension in humans.
      Increased expression of the gene in the kidney may be the mechanism through which
      some allelic variants of the gene raise blood pressure in rodent models. In this
      study we also demonstrate that the SA gene is expressed in human kidneys.

PMID- 8135834
TI  - Calcitonin directly acts on mouse osteoblastic MC3T3-E1 cells to stimulate mRNA
      expression of c-fos, insulin-like growth factor-1 and osteoblastic phenotypes
      (type 1 collagen and osteocalcin).
AB  - The present study was performed to examine whether calcitonin directly acted on
      mouse osteoblastic MC3T3-E1 cells to stimulate the mRNA expression of insulin
      like growth factor-1 (IGF-1) and c-fos, followed by an increase in their
      proliferation and differentiation. Eel calcitonin increased [3H]thymidine
      incorporation and alkaline phosphatase activity as well as the mRNA expression of
      type 1 collagen and osteocalcin which were characteristic of osteoblasts. Eel
      calcitonin (10(-8)M) induced c-fos mRNA transiently after its addition, followed
      by gene expression of IGF-1, an important autocrine/paracrine growth factor in
      the regulation of osteoblastic proliferation. We first demonstrated that
      calcitonin directly acted on osteoblasts to stimulate transcription of c-fos and
      IGF-1 genes as well as functional phenotypes including type 1 collagen and
      osteocalcin.

PMID- 8135835
TI  - Incorporation of phospholipid analogues into the plasma membrane affects ATP
      induced vesiculation of human erythrocyte ghosts.
AB  - The influence of various spin-labelled phospholipid analogues on the ATP
      dependent vesiculation of human erythrocyte ghosts at 37 degrees C was
      investigated by monitoring the acetylcholinesterase activity. After incorporation
      of analogues into the outer leaflet a decline of endocytic vesiculation was
      observed. However, suppression was arrested after about 20 min when ghosts have
      been labelled with a phosphatidylserine analogue known to redistribute rapidly to
      the inner leaflet. These data suggest that vesiculation of erythrocyte ghosts is
      affected by differential expansion of the inner and outer leaflet.

PMID- 8135836
TI  - Sphinganine potentiation of dimethyl sulfoxide-induced granulocyte
      differentiation, increase of alkaline phosphatase activity and decrease of
      protein kinase C activity in a human leukemia cell line (HL-60).
AB  - The differentiation of HL-60 promyelocytic cells toward mature granulocytic cells
      induced by dimethyl sulfoxide (DMSO) was accompanied by a quantitative similar
      increase in alkaline phosphatase (ALP) activity and decrease in protein kinase C
      (PKC) activity. The combination of DMSO and sphinganine (SP), a potent inhibitor
      of PKC, increased in parallel the percentage of mature cells and the ALP
      activity. The enhancement of DMSO-induced differentiation and the potentiation of
      the decrease of PKC activity by SP also seemed to correlate with each other. Our
      results indicate that both ALP and PKC may play a role in the DMSO-induced
      granulocytic differentiation.

PMID- 8135837
TI  - A novel protein kinase with leucine zipper-like sequences: its catalytic domain
      is highly homologous to that of protein kinase C.
AB  - A novel protein kinase, designated PKN, was identified by molecular cloning from
      a human hippocampus cDNA library. PKN consists of 942 amino acids with a
      calculated molecular mass of 103,925 daltons. PKN has leucine zipper-like
      sequences in its amino terminal region and contains a catalytic domain that shows
      strong similarity to that of protein kinase C family. Northern blot analysis
      indicates PKN is expressed ubiquitously in human tissues. Antisera against PKN
      identified a 120K dalton protein on SDS polyacrylamide gel electrophoresis when
      PKN was expressed in the insect cells or COS7 cells. Recombinant PKN revealed an
      intrinsic protein kinase activity associated with a 120K protein. This activity
      was abolished by mutation of the lysine residue in the potential ATP binding
      site.

PMID- 8135838
TI  - Identification of adenosine A2 receptor-cAMP system in human aortic endothelial
      cells.
AB  - The involvement of endothelial adenosine A2 receptor-cAMP system in A2 receptor
      mediated vasodilation in human aortic endothelial cells (HAEC) was investigated.
      Reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression
      of both A2a and A2b receptors mRNA in HAEC. In HAEC, YT-146 (selective A2
      receptor-agonist) produced a dose-dependent increase of cAMP production. This
      increase was inhibited by theophylline. YT-146 also showed a vasodilatory action
      in isolated rat aorta. The removal of endothelium significantly attenuated this
      vasodilatory effect. Our results provide the first evidence for the expression of
      both subtypes of the A2a and A2b receptors which regulate cAMP production in
      human endothelial cells. The present results also suggest that A2 receptor-cAMP
      system was involved in the endothelium-dependent vasodilatory actions and may
      play important roles in regulating vascular functions of HAEC.

PMID- 8135839
TI  - Multiple-channel fractal information coding of mammalian nerve signals.
AB  - As an average of minimal 3 to maximal 30 single auditory-nerve fibers converge in
      the auditory pathway, the fractal geometry of their signals is transformed to a
      different fractal geometry such that small variations of the primary discharge
      patterns correspond to large variations of the combined signal. The addition of
      white noise does not affect the fractal signal structure. The quality of the
      transsynaptic information transfer depends on the relation between the number of
      the convergent spike trains and the individual fractal geometries of the
      convergent spike trains.

PMID- 8135840
TI  - The importance of the hydroxyl moieties for inhibition of the Ca(2+)-ATPase by
      trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone.
AB  - Trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone (BHQ) are potent
      inhibitors of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum.
      Desoxytrilobolide and 2,5-di(tert-butyl)-1,4-diacetylphenol (acetyl-BHQ) have
      much lower potencies than their parent compounds and 2,5-di(tert-butyl)-1,4
      benzoquinone (BQ) has no effect on ATPase activity. Studies using the ATPase
      labelled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) suggest that both trilobolide
      and BHQ bind more strongly to the E2 conformation of the ATPase than to the E1
      conformation. Desoxytrilobolide, acetyl-BHQ and BQ have little effect on the
      E1/E2 equilibrium. Studies with mixtures of trilobolide and desoxytrilobolide
      suggest that the inactive derivatives are unable to bind to the ATPase.

PMID- 8135841
TI  - Epidermal growth factor and insulin-like growth factor I differently influence
      the directional accumulation and transfer of 2-aminoisobutyrate (AIB) by human
      placental trophoblast in two-sided culture.
AB  - We examined the effects of epidermal growth factor (EGF) and insulin-like growth
      factor I (IGF-I) on the uptake of AIB by and its transfer across near-term human
      placental syncytiotrophoblast in two-sided culture. Pre-incubation of the
      trophoblast cell layer with either EGF (50ng/ml) or IGF-I (100ng/ml) on the
      apical (microvillous, in vivo maternal-facing) side reduced rates of
      unidirectional microvillous-to-basal transtrophoblast AIB transfer, increasing
      AIB retention within the cells. EGF on the basal (fetal-facing) side of the cell
      layer enhanced AIB uptake from the microvillous side but also increased overall
      mediated permeability in both directions. IGF-I at the basal surface, however,
      increased AIB uptake across the microvillous membrane, and induced a backflux
      from the cells into the basal medium dependent upon basal AIB concentration,
      suggesting that in vivo IGF-I on the fetal side enhances maternal-to-fetal
      placental transfer. The ideas are consistent with current concepts of maternal
      placental and fetal-placental interactions regulating pregnancy and fetal
      development.

PMID- 8135842
TI  - Ipriflavone directly inhibits osteoclastic activity.
AB  - Ipriflavone, an isoflavone derivative, is a new drug used in an attempt to
      decrease bone loss in osteoporosis. Experimental studies have shown that this
      compound acts by inhibiting osteoclastic bone resorption both in vivo and in
      vitro, but the mechanism of its inhibitory action on resorbing cells remains
      unclear. Using bone resorption assays, video image analysis together with
      measurements of intracellular free calcium in isolated osteoclasts, we show here
      that IP directly inhibits osteoclastic activity by the modulation of
      intracellular free calcium.

PMID- 8135843
TI  - The protein kinase C inhibitor ilmofosine (BM 41 440) arrests cells in G2 phase
      and suppresses CDC2 kinase activation through a mechanism different from that of
      DNA damaging agents.
AB  - The thioether phospholipid derivative ilmofosine (BM41440), a selective inhibitor
      of protein kinase C, is a new anticancer drug presently undergoing Phase II
      clinical trials. We have examined the influence of the compound on cell cycle
      progression. Ilmofosine was found to induce a dose-dependent accumulation of CA46
      cells in G2-phase of the cell cycle. G2-arrest correlated with suppression of
      cdc2 kinase activation. Ilmofosine did not affect cdc2 kinase activity in vitro,
      consistent with an indirect locus of action. Ilmofosine treated CA46 cells failed
      to accumulate hyperphosphorylated-cdc2/cyclin B1 complexes that are observed when
      G2-arrest is induced by either nitrogen mustard or ionizing radiation. Indeed,
      cdc2 became dephosphorylated and cyclin B1 protein levels decreased as ilmofosine
      treated cells became arrested in G2. Our findings suggest that ilmofosine down
      regulates cdc2 kinase activation through a mechanism that affects the formation
      of cdc2/cyclin B1 complexes.

PMID- 8135844
TI  - Activation of the non-actomyosin component of aortic wall contraction by phorbol
      ester.
AB  - The mechanisms of smooth muscle tissue contractile system functioning are in many
      respects unexplained. According to the existing hypothesis, the mechanism of
      smooth muscle contraction is based on the interaction between myosin and actin.
      The change of muscle tissue stiffness during the contractive process is the
      important and obligatory feature of this actomyosin interaction. Earlier we have
      shown that, together with the smooth muscle cells, the connective tissue matrix
      can also produce the active mechanical strength. This process is not accompanied
      by changes of stiffness. We suggested that in some cases the induced contraction
      of smooth muscles is fulfilled, entirely or in part, by the connective tissue
      matrix. We report here that contractive reaction induced by the phorbol ester-
      activator of protein kinase C, which is one of the most important enzymes
      involved in the regulation of the smooth muscle contraction--occurs without any
      stiffness changes. The results obtained can not be explained in terms of the
      generally accepted hypothesis of actomyosin interaction. The conclusion is made
      that phorbol ester during the action on the smooth muscle tissue activates the
      mechanical strength generation by the connective tissue matrix.

PMID- 8135845
TI  - Anaplerotic effect of propionyl carnitine in rat heart mitochondria.
AB  - Carnitine and propionyl carnitine both increase production of 14CO2 from [1
      14C]pyruvate but only the latter, in a process inhibited by malonate, increases
      oxygen uptake and 14CO2 evolution from [2-14C]pyruvate. Carnitine increases the
      rate of formation of acetyl carnitine from pyruvate to a greater extent than
      propionyl carnitine. These effects of carnitine and propionyl carnitine are not
      detectable in mitochondria (e.g., rat liver) deficient in carnitine acetyl
      transferase activity.

PMID- 8135846
TI  - Activation of the gene for type-b natriuretic factor in mouse stem cell cultures
      induced for cardiac myogenesis.
AB  - We assessed the temporal transcriptional activity profiles of the genes for type
      B natriuretic factor, BNF, the isoform ANF, and other cardiac muscle proteins in
      differentiating cultures derived from multipotential mouse cell lines. P19
      embryonal carcinoma cells and D3 embryonic stem cells were induced for in vitro
      cardiac myogenesis; RNA was isolated at regular intervals throughout the
      differentiation programs, and mRNAs were detected by reverse transcriptase
      mediated polymerase chain reactions. The transcriptional activation profiles of
      the ANF and BNF gene were similar, but there were quantitative differences that
      were best assayed by use of competitive internal DNA standards. The levels of
      induced BNF transcripts were highest in the P19 developmental system reaching
      approximately 10% of adult mouse ventricular muscle levels; those for ANF were
      lower, but also readily detected. The cell lines may be used to define the
      regulatory control elements for natriuretic factor gene expression, in stably
      transfected cell lines, during cardiac muscle growth.

PMID- 8135847
TI  - Effect of erythropoietin on DNA synthesis, proto-oncogene expression and
      phospholipase C activity in rat vascular smooth muscle cells.
AB  - The administration of recombinant human erythropoietin (rHuEpo) to anemic chronic
      renal failure patients may be associated with an increase in blood pressure,
      possibly by direct effects on peripheral blood vessels. The experiments of the
      present study were designed to explore the hypothesis that rHuEpo might exert
      mitogenic effects on vascular smooth muscle cells (VSMCs), and that pre-existing
      hypertension might be a predisposing condition. Cultured aortic VSMCs from
      spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were
      studied for DNA synthesis, phospholipase C activity, and cell growth related
      proto-oncogene expression in the presence of rHuEpo. In cells from both rat
      strains, rHuEpo dose-dependently increased DNA synthesis and stimulated
      phospholipase C activity, as indicated by 3H-thymidine incorporation and inositol
      phosphate formation, respectively. Exposure of VSMCs to rHuEpo for various
      periods gradually increased the levels of c-myc and JunB mRNAs and transiently
      induced c-fos mRNA expression as determined by Northern analysis. The hormone
      induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those
      from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene
      expression did not differ between the two strains. Taken together, these results
      suggest that rHuEpo may function as a vascular smooth muscle cell growth
      promoting factor through activation of the phospholipase C cascade and a
      modulation of proto-oncogene expression. It could thereby contribute to vascular
      hypertrophy and arterial hypertension.

PMID- 8135848
TI  - Endothelin-1 stimulates cytosolic phospholipase A2 in Chinese hamster ovary cells
      stably expressing the human ETA or ETB receptor subtype.
AB  - The ability of endothelin-1 (ET-1) to activate cytosolic phospholipase A2 (cPLA2)
      has been studied in Chinese Hamster ovary (CHO) cells stably expressing either
      the human ETA (CHO/ETA) or the human ETB (CHO/ETB) receptor subtype. ET-1 dose
      dependently increased a dithiothreitol-insensitive cPLA2 activity in both cell
      types. In CHO/ETA cells, BQ-123, an ETA-selective antagonist, completely blocked
      ET-1-induced cPLA2 stimulation. In CHO/ETB cells, the ET-1 response was mimicked
      by 4AlaET-1 which could be blocked partially by PD 145065, a nonselective
      antagonist of ETA and ETB. As expected, ET-1 stimulated PGE2 synthesis in CHO
      cells transfected with ET receptors. We conclude that ET-1 can stimulate cPLA2
      via both the human ETA and ETB receptor subtype.

PMID- 8135849
TI  - Molecular cloning, tissue expression of human xanthine dehydrogenase.
AB  - Xanthine dehydrogenase (XDH, EC 1.1.1.204) is a molybdenum iron-sulphur flavin
      hydroxylase which oxidizes a variety of purines, pterins and other heterogenic
      nitrogen compounds, serving as a rate-limiting enzyme in nucleic acid
      degradation. In this work, we have isolated and sequenced cDNA clones of human
      liver XDH. The obtained cDNA covers 4577 bases of human liver XDH mRNA with a 63
      bp 5'-end untranslated region and a 515 bp 3'-end untranslated region. A
      termination codon TGA and a polyadenylation signal AATAAA were identified. An
      open reading frame encodes 1333 amino acid residues. The assignment of the N
      terminal was confirmed by directly sequencing that region of purified human milk
      XDH. Northern blot analysis shows that the human XDH gene is widely expressed in
      human tissues.

PMID- 8135850
TI  - Thermodynamic studies of enzyme catalysis. What can we learn about specificity
      and mechanism?

PMID- 8135851
TI  - Amiloride-sensitive sodium uptake into human placental brush border membrane
      vesicles.
AB  - Sodium transport into human placental brush border membrane vesicles was examined
      in the presence of an outwardly directed sodium gradient leading to the formation
      of an intravesicular negative charge. 22Na entered the vesicles in a time
      dependent fashion. The activation energy of the uptake process was calculated and
      was found to be 11.2 kcal/mol, similar to the value of ionic diffusion in free
      solution. Amiloride inhibited Na uptake in a concentration dependent fashion with
      an IC50 value of 3.08 microM. Neither ouabain nor bumetanide had an effect on Na
      uptake at concentrations up to 100 or 1000 microM, respectively. The system
      presented here indicates Na transport via channels without involvement of the Na
      K-ATPase or the Na-K-Cl cotransporter. The system may be useful in investigating
      Na transport defects in cystic fibrosis.

PMID- 8135852
TI  - A comparative study of constitutive and induced alkoxyresorufin O-dealkylation
      and individual cytochrome P450 forms in cynomolgus monkey (Macaca fascicularis),
      human, mouse, rat and hamster liver microsomes.
AB  - The expression of constitutive and inducible cytochrome P450 forms was measured
      in cynomolgus monkey liver and compared with man, rat, mouse and hamster. Four
      alkoxyresorufin O-dealkylation (AROD) activities widely used as indicators of
      P450 induction were measured: methoxyresorufin O-demethylation (MROD),
      ethoxyresorufin O-deethylation (EROD), pentoxyresorufin O-dealkylation (PROD) and
      benzyloxyresorufin O-dealkylation (BROD). In monkeys there were no sex
      differences in untreated, phenobarbitone (PB)- or beta-naphthoflavone (BNF)
      treated animals in AROD activities, or in individual P450 proteins detected by
      immunoblotting. Basal MROD and EROD activities varied by less than 7-fold between
      the five species, but the comparative pattern of basal MROD, EROD, PROD and BROD
      activities (the "MEPB profile") was very species-specific, with monkeys being
      similar to rats but different from man, mouse and hamster. The induction of AROD
      activities by PB and BNF was also highly species-specific. Monkeys expressed
      constitutive proteins immunorelated to the CYP1A, CYP2A, CYP2B, CYP2C and CYP3A
      sub-families (human CYP2A6 cross-reacted with the anti-rat CYP2B1 antibodies
      used, and so CYP2A and CYP2B forms could not be separately identified in the
      monkey). Single constitutive immunoblot bands were identified in monkey for CYP1A
      (54 kDa), CYP2A/CYP2B (51 kDa) and CYP3A (51 kDa), respectively, but two strong
      (51 and 52 kDa) plus two weak (49 and 49.5 kDa) bands were shown for CYP2C. Human
      liver expressed CYP1A2 (54 kDa), CYP2A6 (51 kDa), CYP3A4 (50.5 kDa) and three
      CYP2C9-immunorelated protein bands (48, 50 and 54 kDa). In monkeys BNF induced
      the 54 kDa CYP1A protein and CYP1A-dependent MROD, EROD and PROD activities (18-,
      15- and 6-fold increases in activity, respectively), whereas PB strongly induced
      the 51 kDa CYP2A/CYP2B protein but did not induce PROD activity. PB also induced
      non-constitutive CYP2A/CYP2B protein bands at 49 and 52 kDa in some monkeys. BROD
      activity was induced less that four-fold by either PB or BNF in monkeys. In
      conclusion, cynomolgus monkeys expressed a range of constitutive CYP1A, CYP2A or
      CYP2B, CYP2C and CYP3A proteins similar to man, and a range of AROD monooxygenase
      reaction rates similar to both man and rat, but the basal MEPB profile of AROD
      activities in monkeys was more similar to rat than to man. MROD and EROD were
      good measures of CYP1A induction by polycyclic aromatic hydrocarbons in
      cynomolgus monkeys, but neither PROD nor BROD were indices of CYP2B induction by
      PB.

PMID- 8135853
TI  - Characterisation of the unusual expression of cross resistance to cisplatin in a
      series of etoposide-selected resistant sublines of the SuSa testicular teratoma
      cell line.
AB  - Three etoposide-selected resistant sublines of the SuSa testicular teratoma cell
      line expressing 9-, 21- and 33-fold levels of resistance, proved increasingly
      cross resistant to cisplatin with levels approximating to 3-, 4- and 6-fold in
      sublines VPC2, VPC3 and VPC4, respectively. Cisplatin resistance was not
      associated with any significant modifications in levels of total glutathione or
      associated enzyme activities. Decreased platinum (Pt) accumulation was detected,
      although this did not correlate either with total platination levels judged
      immunochemically or with peak induction of interstrand crosslinks (ISC)
      determined by alkaline elution. Following exposure to cisplatin in the least
      resistant subline, VPC2, total platination levels were markedly decreased (3
      fold) relative to those of the parental cells, whilst peak ISC levels were
      markedly increased (4-fold). In the most highly resistant subline, VPC4, peak
      levels of ISCs were even higher (9-fold), although total platination levels
      remained comparable with those in parental cells. Both VPC2 and VPC4 cells
      appeared highly proficient in removing ISCs, unlike the parental cells. However,
      whilst VPC2 cells appeared to share deficient removal of the intrastrand
      platinated lesions with parental cells, VPC4 cells proved proficient in removing
      specific adducts in the sequence pApG. This unusual expression of cross
      resistance to cisplatin in a series of etoposide-selected resistant sublines
      derived from an inherently repair deficient parental cell line, SuSa, therefore
      appears to be associated with enhanced removal of the specific intrastrand
      crosslinks in the sequence pApG and/or of DNA-DNA ISCs. Similar mechanisms have
      been implicated in two other cisplatin resistant SuSa sublines selected following
      in vitro exposure to the drug itself or to fractionated X-irradiation.

PMID- 8135854
TI  - Phosphodiesterase inhibitory profile of some related xanthine derivatives
      pharmacologically active on the peripheral microcirculation.
AB  - The cyclic nucleotide phosphodiesterase (PDE) inhibitory profile of four related
      xanthine derivatives: pentoxifylline (BL 191), propentofylline (HWA 285),
      torbafylline (HWA 448) and albifylline (HWA 138), pharmacologically active on the
      peripheral and/or cerebral microcirculation was established using the four main
      PDE isoforms present in rat heart cytosol. HPLC on a Mono Q ion-exchange column
      resolved four separate cyclic nucleotide PDE activities: a calmodulin-activated
      fraction (PDE I), a cGMP-stimulated fraction (PDE II), a cAMP-specific rolipram
      sensitive fraction (PDE IV) and a cGMP-inhibited fraction (PDE III). Among the
      four compounds studies, only torbafylline and pentoxifylline inhibited more
      efficiently the calcium plus calmodulin-stimulated than the basal activity of PDE
      I. The four xanthine derivatives inhibited more potently the cGMP-stimulated than
      the basal activity of the cGMP-stimulatable PDE II, propentofylline being the
      most inhibitory (IC50: 20 microM). Except for propentofylline, which exhibited a
      marked selectivity toward the rolipram-sensitive PDE versus the cGMP-inhibited
      PDE III, the other xanthines modestly (IC50 in the 10(-4) M range) inhibited both
      cAMP-specific isoforms with similar potency. Propentofylline proved to be the
      best inhibitor whatever the considered isoform whereas torbafylline exhibited the
      weakest inhibitory potency with, however, some selectivity for PDE I.

PMID- 8135855
TI  - Mechanism of inhibitory effects of chelating drugs on lipid peroxidation in rat
      brain homogenates.
AB  - The mechanism of the inhibitory effects of chelators (desferrioxamine, EDTA,
      rutin, phenanthroline and ADP) on the production of oxygen radicals in the Fenton
      reaction and on lipid peroxidation of rat brain homogenates has been studied. It
      was found that the inhibitory effects of the chelators correlated well with their
      abilities to oxidize ferrous ions in solution and brain homogenates. On these
      grounds, it was concluded that the oxidation of Fe2+ ions inside a ferrous ion
      chelator complex is a major mechanism of inhibitory effects of these chelators on
      free radical processes. It is proposed that this mechanism is also realized
      during therapeutic treatment with chelators of patients with "free radical"
      pathologies such as Fanconi anemia, beta-thalassemia and Diamond-Blackfan anemia.

PMID- 8135856
TI  - Functional characterization of the A2b adenosine receptor in NIH 3T3 fibroblasts.
AB  - The adenosine (ADO) receptor in NIH 3T3 fibroblasts was characterized using a
      series of adenosine agonists and selected xanthine and non-xanthine antagonists.
      The ADO receptor elicited accumulations of cyclic AMP in intact NIH 3T3
      fibroblasts and caused activation of adenylate cyclase in membrane preparations.
      The receptor had characteristics of the A2b subtype of adenosine receptor. ADO
      analogs had relatively high EC50 values at the receptor and were antagonized
      competitively by xanthines. The rank order of potency for adenosine analogs in
      NIH 3T3 fibroblasts for cyclic AMP accumulation was: NECA > 2-ClADO > R-PIA >>
      CV1808, CGS 21680. The EC50 for 2-ClADO was 4.3 microM in intact cells and 15
      microM in membrane preparations. All ADO analogs were more potent at the A2a
      receptor of pheochromocytoma PC12 membranes than at the A2b receptor of
      fibroblast NIH 3T3 membranes. Structure-activity relationships suggested that the
      regions of interaction with 5'- and N6-substituents of ADO were similar for both
      the PC12 A2a and NIH 3T3 A2b receptor. However, ADO analogs with large
      substituents in the 2'-position, such as 2-cyclohexylethoxy ADO and CGS 21680,
      were highly selective for the A2a receptor. All ADO analogs tested were
      stimulatory to adenylate cyclase at the NIH 3T3 A2b receptor, including 5'
      methylthioADO, which was a weak partial agonist. A series of xanthine antagonists
      were not selective for the NIH 3T3 A2b versus the PC12 A2a receptor. In all
      cases, xanthines were more potent as antagonists in the intact NIH 3T3 cells than
      in NIH 3T3 membranes. In a series of non-xanthine antagonists, most compounds
      were equipotent or slightly more potent at the A2a receptor except for
      alloxazine, which was approximately 9-fold selective for the A2b receptor.

PMID- 8135857
TI  - Stimulation of weak organic acid uptake in rat renal tubules by cadmium and
      nystatin.
AB  - The uphill uptake of a weak organic acid, fluorescein, in superficial proximal
      tubules of the rat kidney was stimulated by CdCl2 (0.1 mM) or nystatin (20
      microM) in the absence of metabolic substrates in the incubation medium. The
      stimulation could be observed during the initial period of incubation (up to 30
      min) only and was prevented completely by ouabain (0.1 mM), fluoroacetate (1 mM),
      malonate (10 mM), alpha-cyano-4-hydroxycinnamate (0.1 mM), phenylpyruvate (1 mM),
      D-malate (2 mM) or phenazine methosulfate (20 microM). In the renal cortex
      fragment suspension, both Cd2+ and nystatin increased the ouabain-sensitive,
      basal oxygen consumption and inhibited the rate of glucose production from
      pyruvate, but not from lactate. In the presence of lactate (0.5-5 mM) in the
      incubation medium, Cd2+ and nystatin rather inhibited fluorescein uptake, while
      externally added pyruvate did not influence their stimulatory effects. Taken
      together, these data suggest that both activation of the tricarboxylic acid cycle
      and export of reducing equivalents from the mitochondria to the cytosol are
      necessary for the stimulatory effects of Cd2+ and nystatin on the weak organic
      acid uptake to develop.

PMID- 8135858
TI  - Stimulatory effect of ethanol on weak organic acid uptake in rat renal tubules.
AB  - Ethanol at relatively low concentrations (10-40 mM) significantly stimulated the
      uphill uptake of a weak organic acid, fluorescein, in the superficial proximal
      tubules of rat renal cortex slices, but it did not affect the rate of glucose
      production from lactate or pyruvate in rat renal cortex fragment suspension. In a
      low Na+ medium, ethanol failed to stimulate fluorescein uptake, although under
      the conditions employed in the present study, the baseline weak organic acid
      uptake was not dependent on external Na+. The stimulation of fluorescein uptake
      by ethanol (20 mM) was abolished by an inhibitor of alcohol dehydrogenase (EC
      1.1.1.1), pyrazole (1 mM), or an inhibitor of aldehyde dehydrogenase (EC
      1.2.1.3), cyanamide (0.3 mM), suggesting that oxidation of ethanol mediated its
      effect on the uptake. Among gluconeogenesis inhibitors tested, only D-malate (2
      mM) abolished the stimulatory effect of ethanol, while the rest either did not
      affect (quinolinate) or even slightly augmented (alpha-cyano-4-hydroxycinnamate
      and phenylpyruvate) it. The effect of ethanol was markedly increased by an
      inhibitor of the tricarboxylic acid cycle, fluoroacetate. It was concluded that
      the stimulation by ethanol of weak organic acid uptake in rat renal tubules was
      mediated by the production of acetate.

PMID- 8135859
TI  - Effects of bryostatin 1 and other pharmacological activators of protein kinase C
      on 1-[beta-D-arabinofuranosyl]cytosine-induced apoptosis in HL-60 human
      promyelocytic leukemia cells.
AB  - We have demonstrated previously that bryostatin 1, a macrocylic lactone with
      putative protein kinase C (PKC)-activating properties, synergistically augments
      the antileukemic actions of the deoxycytidine analog 1-[beta-D
      arabinofuranosyl]cytosine (ara-C) in HL-60 human promyelocytic leukemia cells
      (Grant et al., Biochem Pharmacol 42: 853-867, 1991), and that this effect appears
      to be related to sensitization to ara-C-induced apoptosis (Grant et al., Cancer
      Res 52: 6270-6278, 1992). In the present studies, we have assessed the extent of
      this damage by quantitative spectrofluorophotometry of small molecular weight,
      double-stranded DNA fragments in order to provide: (a) a more complete
      characterization of the interaction between ara-C and bryostatin 1, and (b) a
      direct comparison of the relative effects of bryostatin 1 treatment with other
      pharmacological manipulations known to modulate protein kinase C activity.
      Exposure of cells to ara-C (10(-9) to 10(-4) M; 1-24 hr) induced time- and
      concentration-related increases in the extent of DNA fragmentation. Treatment
      with bryostatin 1 (10(-11) to 10(-7) M; 1-24 hr) alone failed to induce DNA
      damage, but promoted substantial time- and concentration-related increases in the
      extent of fragmentation induced by a subsequent 6-hr exposure to ara-C. Maximal
      potentiation of fragmentation (e.g. 2- to 3-fold greater than that obtained with
      ara-C alone) was observed following a 24-hr pretreatment with 10(-8) M or 10(-7)
      M bryostatin 1, and correlated closely with enhanced inhibition of HL-60 cell
      clonogenicity. The stage-1 tumor-promoter phorbol dibutyrate potentiated the
      effects of ara-C in a biphasic manner, maximally augmenting the response at 2.5 x
      10(-8) M, but exerting no effect at 10(-7) M, whereas the stage-2 tumor-promoter
      mezerein failed to augment ara-C-related DNA fragmentation at low concentrations,
      and antagonized ara-C action at high concentrations. In contrast, ara-C-related
      DNA fragmentation was attenuated or abolished either by continual preexposure to
      synthetic diglyceride or by pretreatment with exogenous phospholipase C at all
      concentrations tested. Increased DNA fragmentation was not specifically related
      to recruitment of cells into S-phase or enhancement of ara-C-related cellular
      differentiation. Finally, concentrations of bryostatin 1 that maximally
      potentiated ara-C-related DNA fragmentation were associated with virtually
      complete down-regulation of total cellular PKC activity, whereas diglyceride and
      phospholipase C, which suppressed the response to ara-C, moderately increased
      total PKC activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8135860
TI  - Targeted delivery of superoxide dismutase to macrophages via mannose receptor
      mediated mechanism.
AB  - Human recombinant superoxide dismutase (SOD) was modified into a mannosylated
      form (Man-SOD), and its cellular uptake and inhibitory effect on superoxide anion
      release were studied in vitro, using cultured mouse peritoneal macrophages.
      [111In]Man-SOD was taken up by the macrophages to a great extent, whereas no
      significant uptake was observed for native and galactosylated SOD. The uptake of
      Man-SOD was inhibited significantly at a low temperature and by the presence of
      mannan, mannose and colchicine, demonstrating the targeted delivery of Man-SOD
      via mannose receptor-mediated endocytosis. Man-SOD exhibited a superior
      inhibitory effect on superoxide anion release from inflammatory macrophages
      stimulated by phorbol-myristate acetate. The present study suggested the
      potential of Man-SOD as a therapeutic agent for the inflammatory disease mediated
      by superoxide anions generated by macrophages.

PMID- 8135861
TI  - Comparison of sulfur amino acid utilization for GSH synthesis between HepG2 cells
      and cultured rat hepatocytes.
AB  - HepG2 cells are widely used as a model of human hepatocytes for studies of drug
      metabolism and toxicity. However, GSH metabolism in HepG2 cells is poorly
      characterized. This report describes the utilization of sulfur amino acids for
      GSH synthesis in HepG2 cells. In contrast to primary cultures of rat hepatocytes,
      which rely mostly on methionine for GSH synthesis, HepG2 cells use cystine. Their
      inability to utilize methionine for GSH synthesis was not due to lack of
      methionine uptake or low cellular ATP levels, but rather to the lack of S
      adenosyl-methionine synthetase activity. When HepG2 cells were cultured overnight
      in medium containing cystine as the only sulfur amino acid, addition of glutamate
      or acivicin had minimal to no effect on cell GSH; however, addition of threonine
      significantly depleted cell GSH. When cystine (0.18 mM) uptake was measured,
      glutamate (2.5 mM), which inhibited cystine uptake in cultured rat hepatocytes,
      had a minimal effect in HepG2 cells. Instead, threonine (20 mM) strongly
      inhibited the apparent uptake of cystine by HepG2 cells. Strong inhibition by
      threonine of apparent cystine uptake was actually due to inhibition of cysteine
      uptake, which resulted from GSH-cystine mixed disulfide exchange. Radio-HPLC
      confirmed this. After incubating cells with [35S]cystine (0.18 mM) for 10 min,
      the total counts inside the cell matched the counts in the uptake medium in the
      form of GSH-cysteine mixed disulfide. Finally, HepG2 cells took up cysteine by
      both Na(+)-dependent and -independent mechanisms. The former exhibited high
      affinity and low capacity, whereas the latter exhibited the opposite. At a
      physiologic concentration of cysteine (10 microM), 68% of cysteine uptake
      occurred via the Na(+)-dependent system and 32% via system L1.

PMID- 8135862
TI  - Antiperoxide activity of sodium metabisulfite. A double-edged sword.
AB  - Sulfites are chemical substances that are used widely in the pharmaceutical
      industry to reduce or prevent oxidation. Sodium metabisulfite (Na2S2O5) is still
      present in several parenteral amino acid solutions. Since intravenous lipid
      emulsions are contaminated by hydroperoxides, we evaluated whether metabisulfite
      had an antioxidant activity against hydroperoxides. In vitro, Na2S2O5 inhibited
      the oxidant activity of H2O2, tert-butyl-, and cumene hydroperoxides. The
      antioxidant capacity of metabisulfite was supported in vivo by the lower (P <
      0.01) excretion of malondialdehyde, a stable end product of lipid peroxidation,
      in babies receiving metabisulfite in their parenteral nutrition. However, for
      concentrations outside the range found in solutions for parenteral nutrition, the
      reduction of hydroperoxides by Na2S2O5 could transform this compound into an
      oxidant, like a sulfite radical. It is suggested that metabisulfite has
      antiperoxide properties that, under specific conditions, contribute to the
      generation of toxic oxidants.

PMID- 8135863
TI  - Effects of Adriamycin on heart mitochondrial function in rested and exercised
      rats.
AB  - The effect of Adriamycin (ADM) administration on heart mitochondria was
      investigated in rats at rest and after an acute bout of maximal exercise. ADM was
      given intravenously at a dosage of 8 mg/kg body weight 24 and 1 hr before rats
      were decapitated. Respiratory functions of the isolated heart mitochondria were
      measured polarographically with both site 1 (pyruvate-malate and 2-oxoglutarate)
      and site 2 (succinate) substrates. State 4 (basal) respiration was increased
      using all substrates in ADM-treated rat hearts compared with non-drug control
      hearts. The mitochondrial respiratory control index was decreased with ADM, but
      the reduction was due to an increase in state 4 rather than a decrease of state 3
      (ADP-stimulated) respiration. ADM administration abolished an exercise-induced
      elevation of state 3 respiration using all substrates. There was no significant
      myocardial oxidative damage of dysfunction as evaluated by lipid peroxidation and
      antioxidant enzyme activity. Addition of exogenous free radicals to the
      respiratory medium using hypoxanthine and xanthine oxidase resulted in
      significant deterioration of mitochondrial function in all parameters measured,
      but no drug- or exercise-specific patterns of damage were revealed. It is
      concluded that the current dose of ADM (20% of the established cumulative toxic
      dose) administered within 24 hr can interfere with normal heart mitochondrial
      function both at rest and during heavy exercise, but does not elicit overwhelming
      oxidative damage to the myocardium.

PMID- 8135864
TI  - Absence of antioxidant effects of nifedipine and diltiazem on myocardial membrane
      lipid peroxidation in contrast with those of nisoldipine and propranolol.
AB  - Both the production of active oxygen species and cellular damage due to
      concurrent lipid peroxidation are believed to be important factors in the
      pathogenesis of cardiovascular diseases and the ageing process. Since
      cardiovascular drugs are often administered over a long term, it might be
      advantageous if they reduced lipid peroxidation. There have been conflicting
      reports concerning the antiperoxidant effect of nifedipine. Therefore, we
      investigated whether nifedipine could inhibit lipid peroxidation in a
      nonenzymatic active oxygen-generating system, utilizing rat crude myocardial
      membranes, and compared its effect with those of propranolol, nisoldipine, and
      diltiazem. Nifedipine and diltiazem had no inhibitory effects on the lipid
      peroxidation of myocardial membranes. In contrast, nisoldipine and propranolol
      had a concentration-dependent antiperoxidant effect, with IC50 values of 28.2 and
      50.1 microM, respectively. In addition, nisoldipine appeared to possess dual
      antiperoxidant mechanisms, involving both preventive and chain-breaking
      properties.

PMID- 8135865
TI  - Use of 7-alkoxyphenoxazones, 7-alkoxycoumarins and 7-alkoxyquinolines as
      fluorescent substrates for rainbow trout hepatic microsomes after treatment with
      various inducers.
AB  - Various fluorescent substrates have been used as specific indicators of induction
      or activity of different cytochrome P450 isozymes in both fish and mammalian
      species. In an attempt to identify additional definitive fluorescent substrates
      for use in fish, we examined a series of 7-alkoxyphenoxazones, 7-alkoxycoumarins
      and 7-alkoxyquinolines as substrates in O-dealkylation assays with hepatic
      microsomes from rainbow trout (Oncorhynchus mykiss). Microsomes were prepared
      after 48 hr of treatment with beta-naphthoflavone (beta-NF), pregnenolone-16
      alpha-carbonitrile (PCN), phenobarbital (PB), isosafrole (ISF), or dexamethasone
      (DEX). Total P450 spectra were obtained, and spectral binding studies were
      performed. Microsomal O-dealkylation rates were greater after ISF treatment than
      after beta-NF treatment for 7-methoxy-, 7-ethoxy-, 7-propoxy- and 7
      benzyloxyphenoxazones but not for 7-butoxyphenoxazone. DEX treatment resulted in
      a significant elevation of pentoxyphenoxazone metabolism (about a 144-fold
      increase) compared with microsomes induced by beta-NF (11-fold) and ISF (37
      fold). The rates of dealkylation of the alkoxyphenoxazones by ISF-treated
      microsomes occurred in the following order: methoxy > ethoxy > propoxy >
      benzxyloxy > butoxy > pentoxy. When beta-NF-treated microsomes were used, the 7
      alkoxyphenoxazones were metabolized as follows: methoxy > ethoxy > propoxy >
      butoxy > benzyloxy = pentoxy, while the order of metabolism of the 7
      alkoxycoumarins was: ethoxy >> butoxy > propoxy = methoxy > benzyloxy > pentoxy.
      None of the other treatments significantly increased the rate of metabolism of
      any of the alkoxycoumarins. Treatment with beta-NF did not significantly elevate
      the rate of metabolism of any of the alkoxyquinolines. DEX treatment produced
      significant elevations in the rate of metabolism of benzyloxy-, ethoxy-, and
      butoxy- = pentoxy- = propoxyquinoline, in that order. ISF treatment significantly
      elevated the rate of metabolism of benzyloxy-, methoxy- and butoxyquinoline, in
      that order. These results suggest that some of these new fluorescent substrates
      can be used to characterize induction of rainbow trout hepatic microsomal
      monooxygenase activity by ISF and DEX, in addition to the commonly used
      ethoxyphenoxazone and ethoxycoumarin for the characterization of induction by
      beta-NF or other 3-methylcholanthrene-type P450 inducers. Distinction between ISF
      type and beta-NF-type inducers in rainbow trout hepatic microsomes may best be
      made using 7-methoxycoumarin as a substrate. Distinction between ISF-type and DEX
      type inducers and between beta-NF-type and DEX-type inducers may best be made
      using 7-methoxyphenoxazone as a substrate.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8135866
TI  - Retinal dehydrogenation and retinoic acid 4-hydroxylation in rat hepatic
      microsomes: developmental studies and effect of foreign compounds on the
      activities.
AB  - All-trans-retinoic acid (RA) regulates the transcription of a number of mammalian
      genes and is therefore important in the control of many cellular processes. RA is
      formed and deactivated within the cell so that biotransformation modulates RA
      availability. This study investigate the relationship between the formation of RA
      from retinal and its metabolism by 4-hydroxylation in rat hepatic microsomes.
      From kinetic studies the Michaelis constants for RA formation and 4-hydroxylation
      were 52 and 24 microM, respectively, and the maximal reaction velocities were 33
      and 136 pmol/min/mg protein, respectively. Thus, 4-hydroxylation was the more
      efficient process. In microsomes from 1-week-old rats, RA formation was very low
      (approximately 2 pmol/min/mg protein) but was several-fold greater in adults of
      both sexes (approximately 10 pmol/min/mg protein). In contrast, 4-hydroxylation
      was quantitatively more significant at all ages examined between 1 and 15 weeks;
      by 10 and 15 weeks a sexual dimorphism was apparent (M > F). Thus, the ratio of
      RA 4-hydroxylation to RA formation was comparatively large in microsomes from 1
      week-old rats and declined to a stable value around 4-6 weeks of age. With the
      exception of dexamethasone, which decreased the activity, administration of
      foreign compounds to male rats had little effect on RA formation. Both
      dexamethasone and phenobarbital induced RA 4-hydroxylation but DMSO and beta
      naphthoflavone were without effect. From these findings, 4-hydroxylation,
      particularly in very young animals, may be an effective means of controlling RA
      production. RA 4-hydroxylation, like other cytochrome P450 activities, was
      inducible in rat liver but no evidence was found for induction of the microsomal
      retinal dehydrogenase.

PMID- 8135867
TI  - Effects of chronic prenatal, neonatal and adult exposure to barbiturates on
      mitochondrial benzodiazepine receptors in mouse testis.
AB  - In the present study we investigated the effect of chronic exposure to
      phenobarbital, administered to mice during the prenatal or neonatal period, as
      well as to adult mice, on mitochondrial benzodiazepine receptors in the testis.
      Three modes of treatment were investigated: (1) offspring of pregnant mice
      receiving food containing 3 g/kg phenobarbital until gestational day 18 were
      killed at 22 or 50 days of age and assayed for receptor binding (prenatal group);
      (2) offspring of untreated mice were injected subcutaneously once daily with 50
      mg/kg phenobarbital on days 2-21 of age and killed at 22 or 50 days of age
      (neonatal group); (3) adult mice were injected subcutaneously once daily for 3
      weeks with 50 or 100 mg/kg phenobarbital (adult group). Prenatal or neonatal
      exposure to phenobarbital did not alter the testicular weight in all groups
      (except for the neonatally exposed group killed at 22 days of age), or the
      mitochondrial benzodiazepine receptor binding characteristics. However, the
      maximal number of these receptors in the testes of mice in the adult group
      receiving 100 mg/kg phenobarbital was significantly increased (42%, P < 0.05),
      compared to controls. The administration of 50 mg/kg phenobarbital to the adult
      group also induced an increase (27%, non-significant) in testicular mitochondrial
      benzodiazepine receptors. Phenobarbital administration did not affect the
      receptor affinity values or the weight of the testis. It is unclear whether these
      receptor alterations due to chronic phenobarbital exposure of adult mice reflect
      functional changes in the testis.

PMID- 8135868
TI  - Expression of monomorphic and polymorphic N-acetyltransferases in human colon.
AB  - The metabolism of sulfamethazine (SMZ) and p-aminobenzoic acid (PABA) by N
      acetyltransferase (NAT) was measured in human colorectal cytosols from 12 slow
      and 11 rapid acetylators whose genotype was determined independently by a
      specific polymerase chain reaction. SMZ metabolism was significantly greater in
      the rapid than in the slow phenotype (192 +/- 22 versus 94 +/- 11 pmol N
      acetylsulfamethazine/min/mg protein), while PABA metabolism was similar in both
      phenotypes (23.7 +/- 4.4 versus 23.0 +/- 3.9 nmol N-acetyl-p-aminobenzoic
      acid/min/mg protein). Both monomorphic and polymorphic NAT mRNAs were detected by
      the polymerase chain reaction in the colorectal mucosa of most samples. The
      finding that polymorphic NAT is expressed in a phenotype-dependent manner in
      colorectal mucosa indicates that this tissue has the capacity to participate in
      local bioactivation of dietary and environmental aryl- or heterocyclic amine
      carcinogens and may explain, in part, the phenotype-dependent occurrence of
      colorectal cancer.

PMID- 8135869
TI  - Effects of testosterone, hypophysectomy and growth hormone treatment on
      clofibrate induction of peroxisomal beta-oxidation in female rat liver.
AB  - Induction of peroxisomal beta-oxidation by clofibrate under altered hormonal
      states was investigated in female rat liver. Treatment of rats with clofibric
      acid (CPIB) caused a significant increase in hepatic peroxisomal beta-oxidation,
      with female rats being less responsive than males (4.2- vs 12.2-fold increase).
      However, testosterone treatment following ovariectomy of female rats resulted in
      an enhanced response to CPIB, giving an induction (11.7-fold) comparable to that
      seen in male rats. Hypophysectomy of female rats also enhanced the induction (8.2
      fold compared with 5.1-fold), suggesting a suppressive effect of a pituitary
      dependent factor on CPIB induction of peroxisomal beta-oxidation. Continuous
      infusion of growth hormone to the hypophysectomized female rats suppressed the
      enhanced induction nearly to the initial level (6.1-fold). The stimulatory
      effects of testosterone and hypophysectomy on the enzyme induction were additive.
      These findings suggest the involvement of growth hormone, as well as male sex
      hormone, in regulating the responsiveness to CPIB induction of peroxisomal beta
      oxidation in rat liver.

PMID- 8135870
TI  - Involvement of nitroxyl (HNO) in the cyanamide-induced vasorelaxation of rabbit
      aorta.
AB  - Relaxation of precontracted rabbit aortic rings in vitro by cyanamide, a
      clinically used alcohol deterrent drug, required catalase and H2O2, suggesting
      that a bioactivation mechanism was involved. Since the oxidation of cyanamide by
      catalase/H2O2 had been shown previously to lead to nitroxyl (HNO) generation via
      the intermediate N-hydroxycyanamide, and aortic ring relaxation was inhibited by
      the catalase inhibitor, 3-aminotriazole, HNO appears to be responsible for the
      vasorelaxation mediated by cyanamide. This was further supported by the
      observation that N,O-dibenzoyl-N-hydroxycyanamide (DBHC), a derivative of N
      hydroxycyanamide that releases HNO in the absence of catalase/H2O2, was a potent
      vasorelaxant, with an EC50 of 4.2 +/- 1.3 x 10(-6) M.

PMID- 8135871
TI  - Ethanol-induced suppression of interleukin 1-like activity: reversal by a quinone
      derivative.
AB  - Chronic ethanol intake impairs several parameters of immune function. Since there
      is evidence that cytokine production by immune cells may contribute to the
      immunosuppressive effect of ethanol, we examined interleukin 1 (IL1) production
      by liver non-parenchymal cells (NPC) in ethanol-fed rats. Male Wistar rats (225
      250 g) were fed by continuous intragastric infusion. The source of fat was either
      saturated fat or polyunsaturated fat. In addition, the effect of a quinone
      compound on IL1 production was assessed. Animals were fed for various periods: 1
      week, 2 weeks, 1 month and 2 months. NPC were isolated and stimulated by
      lipopolysaccharide. IL1 production by NPC and the ratio of stimulated to
      unstimulated (S:U) IL1 production were evaluated in the different groups and
      related to the presence of liver injury. As expected, animals fed corn oil and
      ethanol (CO+E) developed pathologic liver injury, whereas animals fed saturated
      fat and ethanol (SF+E) had no liver injury. A progressive decrease in the S:U IL1
      ratio was seen in the CO+E group over the 8-week period. The ratio in the SF+E
      group was higher. The quinone compound reversed the suppressive effect of ethanol
      on IL1 production. In summary, ethanol-induced suppression of IL1 production was
      modulated by diet and the presence of liver injury. This suppression of IL1
      production was reversed by a quinone compound; the exact mechanism for the
      reversal of this inhibition is unknown.

PMID- 8135872
TI  - Escherichia coli as a biologically active ingredient of suppositories. Solid
      phase extraction and quantification in a double antibody ELISA.
AB  - Techniques for isolation and quantification of an active ingredient of biological
      origin from a pharmaceutical product (Posterisan suppositories) were developed.
      By means of ELISA (enzyme-linked immunosorbent assay) in connection with a
      computerized evaluation, the antigenic material, a bacterial culture suspension
      (BCS) of Escherichia coli as a raw material was shown to be specifically and
      reproducibly detectable and quantifiable. As a limit of detection, a bacteria
      concentration of 6 x 10(4) cells/ml was determined, corresponding to 0.02% of the
      concentration in the product. After treating of the suppositories with organic
      solvents, the E. coli antigens were extracted with silica columns. The complete
      validations of both methods, the ELISA itself and the extraction procedure of the
      antigens from the matrix, in accordance with pharmaceutically accepted principles
      are presented. The eventual application of the new technique to the analysis of
      other pharmaceuticals with similar ingredients as well as the possibility of
      substituting conventional methods like total cell counting is discussed.

PMID- 8135873
TI  - Inhibition of platelet aggregation by diterpene acids from Pinus massoniana
      resin.
AB  - The acidic fraction of the resin of Pinus massoniana Lamb. from China was
      converted to the p-nitrophenyl esters, and the esters separated by
      chromatography. The separated p-nitrophenyl esters were individually hydrolysed
      by potassium hydroxide in acetone-water at room temperature to 8 diterpene acids
      of the pimarane and abietane groups: pimaric acid (8(14),15-pimaradien-18-oic
      acid) (1), levopimaric acid (8(14),12-abietadien-18-oic acid) (2), palustric acid
      (8,13-abietadien-18-oic acid) (3), neobietic acid (8(14),13(15)-abietadien-18-oic
      acid) (4), abietic acid (7,13-abietadien-18-oic acid) (5), dehydroabietic acid
      (8,11,13-abietatrien-18-oic acid) (6), 7-oxodehydroabietic acid (7-oxo-8,11,13
      abietatrien-18-oic acid) (7) and 7 alpha-hydroxydehydroabietic acid (7 alpha
      hydroxy-8,11,13-abietatrien-18-oic acid) (8). The structure (and stereochemistry)
      of the diterpene acids were substantiated by nuclear magnetic resonance
      spectroscopy (proton and carbon-13, one and two dimensional), by mass
      spectrometry (electron impact and methane chemical ionization) and by rotation
      measurements. The 8 diterpene acids were tested for their ability to inhibit the
      aggregation of washed rabbit platelets induced by platelet activating factor
      (PAF), adenosine diphosphate (ADP) and by calcium ionophore A23187. With platelet
      aggregation induced by the latter two agonists, activities comparable with or
      higher than linolenic acid were given by the first 4 acids. With aggregation
      induced by PAF, the first 3 acids show activity, but at a level significantly
      lower than that of linolenic acid. Levopimaric acid has the highest activity
      among the diterpene acids tested. It is proposed that this activity is related to
      the folded shape of the molecule.

PMID- 8135874
TI  - Veinotonic effect, vascular protection, antiinflammatory and free radical
      scavenging properties of horse chestnut extract.
AB  - Horse chestnut extract (HCE), containing 70% escin, is the main active component
      of Veinotonyl 75. The aim of this work was to investigate pharmacological
      properties attempting to elucidate the efficacy of HCE in chronic venous
      insufficiency. Veinotonic and lymphagogue properties: HCE dose dependently
      contracts the canine saphenous isolated vein (cumulative doses 5 x 10(-8) to 5 x
      10(-4) g/ml). Its action lasts more than 5 h. In the perfused canine saphenous
      vein, HCE (25-50 mg in bolus) increases the venous pressure of the normal vein
      and the pathological vein stenosed 8 days before, and the contractile response to
      noradrenaline is significantly potentiated. Moreover, during the perfusion in
      inverse direction of the blood stream, a clear contracting effect on the valves
      is also obtained with HCE. In the anaesthetized dog, HCE in situ improves the
      femoral vein compliance and opposes the venous distension obtained during
      clamping in a carotido-femoral perfusion with constant flow. In other respects,
      HCE significantly increases femoral venous pressure and flow, together with
      thoracic lymphatic flow, while respecting the arterial parameters (2.5 and 5
      mg/kg i.v.). Vasculotropic action: HCE dose dependently diminishes the cutaneous
      capillary hyperpermeability induced either by injections of phlogistic agents as
      histamine and serotonin in the rat (100 to 400 mg/kg p.o.), or by an irritative
      agent (chloroform) application in the rabbit (50 to 300 mg/kg p.o. and 2.5 to 5
      mg/kg i.v.). It significantly increases the vascular resistance in the guinea pig
      fed a scorbutigenic diet as measured by the petechia method (50 to 400 mg/kg
      p.o.). Antiedema and antiinflammatory properties: HCE decreases the formation of
      edemas induced in the rat's hind paw, one of lymphatic origin, the other of
      inflammatory origin (200 to 400 mg/kg p.o.). In an experimental model of pleurisy
      in the rat HCE suppresses plasmatic extravasation and leucocytes emigration into
      the pleural cavity (200 to 400 mg/kg p.o.; 1 to 10 mg/kg i.v.). It decreases the
      connective tissue formation in the subchronic model of inflammatory granuloma in
      the rat (400 mg/kg p.o. and 5-10 mg/kg s.c.). Antiradical mechanism of action
      both in vitro and in vivo: HCE dose dependently inhibits both enzymatic and non
      enzymatic in vitro lipid peroxidation (5 x 10(-6) to 5 x 10(-4) g/ml).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8135875
TI  - Calmodulin antagonistic action of new 1,5-benzothiazepines derived from
      diltiazem.
AB  - A series of newly synthesized 1,5-benzothiazepines derived from diltiazem (CAS
      42399-41-7) were tested for calmodulin antagonistic activities using Ca(2+)
      calmodulin stimulated phosphodiesterase (PDE). Some compounds possessing the
      benzoyloxy moieties at position 4 of 1,5-benzothiazepine ring of diltiazem showed
      a dose-dependent inhibitory action with the potencies comparable to that of a
      calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7).
      In contrast, diltiazem did not exert the inhibitory action at the same
      concentrations. Further, radioligand binding experiment, using a radiolabeled 1,5
      benzothiazepine, showed that these compounds bound to Ca(2+)-calmodulin complex,
      but not to calmodulin in the presence of EGTA, suggesting that these 1,5
      benzothiazepines are new calmodulin antagonists. Some of these compounds
      inhibited [3H]diltiazem binding to Ca antagonist binding sites in cell membranes
      of rat cerebral cortex but with a less potent affinities than diltiazem,
      suggesting that there was no correlation between their anti-calmodulin effect and
      the binding affinity to Ca antagonist binding sites. In conclusion, new 1,5
      benzothiazepines have been demonstrated to have an anti-calmodulin action. These
      compounds may possess a pharmacological activity based on their anti-calmodulin
      action in addition to their interaction with Ca channel.

PMID- 8135876
TI  - Effect of vintoperol on platelet aggregation and experimental thrombosis.
AB  - The platelet aggregation inhibitory and antithrombotic effect of the new
      peripheral circulation enhancing compound vintoperol (RGH-2981, CAS 106498-99-1)
      was studied. In vitro, vintoperol inhibited the aggregation response to collagen
      in platelet-rich plasma from mice, rats, rabbits and dogs. It was found to be
      highly effective in preventing mice from acute pulmonary thromboembolic death
      induced by adenosine diphosphate (ADP) or collagen. After the oral dose of 10
      mg/kg the percentage of survivors increased from 9 to 60% and from 13 to 73%,
      respectively. In the "mouse antithrombotic assay" it was protective only at the 3
      mg/kg dose. Sudden death of mice evoked by hardened red blood cell suspension was
      not protected by vintoperol. In mice receiving 30 mg/kg vintoperol orally, the
      inhibition of aggregation response to collagen, ADP and ADP/epinephrine by 15, 33
      and 37%, respectively, was associated with a substantial increase in bleeding
      time. In a rat multifactorial thrombosis model the 10 mg/kg p.o. dose was also
      sufficient to obtain significant antithrombotic effect (p < 0.01). Results of
      these experiments indicate that vintoperol interferes with platelet aggregation
      both in vitro and in vivo and possesses potent antithrombotic effects in
      thrombosis models in which platelet activation is mainly involved.

PMID- 8135877
TI  - Endocrine effects of Lycopus europaeus L. following oral application.
AB  - Lycopus extracts are used in folk medicine for the treatment of hyperthyroid
      symptoms. Diverse effects on the pituitary thyroidal system as well as on the
      pituitary gonadal system could be confirmed in experimental studies. But till now
      endocrine effects of Lycopus extracts in experimental animals were observed after
      parenteral application only. Therefore in this investigation an ethanolic extract
      of Lycopus europaeus was applied orally to rats, diverse endocrine parameters
      were measured between 3 and 24 h later and the effects compared to an i.p.
      treated group. The plant extract given p.o. caused a long lasting (for a period
      of more than 24 h) decrease of T3 levels, presumably as a consequence of a
      reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid
      stimulating hormone (TSH) concentrations was observed 24 h after application of
      the test solution by gavage. The luteinizing hormone (LH) decrease as well as the
      TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate
      a central point of attack of the plant extract. Differences in the biological
      activity in dependence on the route of application may be explained e.g. by
      differences in absorption of plant constituents.

PMID- 8135878
TI  - N4-(arylmethylene)-N1-[1-(1,2,5,6-tetrahydropyridyl)]-sulphanilamide derivatives
      as novel possible hypoglycemic agents.
AB  - Two series of sulphanilamide derivatives (Va-i and Vla-i), comprising both
      azomethine and arylsulphonamidotetrahydropyridine moieties, were especially
      synthesized to investigate the additive effect of such moieties on the
      pharmacological activity of the produced sulphonamides as possible therapeutic
      agents for producing hypoglycemia. Most of the hitherto prepared sulphanilamide
      derivatives, exhibited marked hypoglycemic activity. Structure-activity
      relationships were investigated and discussed, not only on the basis of
      lipophilic (pi) and/or electronic (sigma) characters of the aromatic substituent
      (R), but also in light of a steric effect in these molecules. The structure of
      the newly synthesized compounds was inferred from elemental and spectral
      analysis.

PMID- 8135879
TI  - Mechanism of the inhibition of hog gastric H+,K(+)-ATPase by the seleno-organic
      compound ebselen.
AB  - The effect of 2-phenyl-1,2-benzisoselenazol-3 (2H)-one (ebselen, CAS 60940-34-3),
      a seleno-organic compound, on the partial reaction steps of H+,K(+)-ATPase in hog
      leaky gastric vesicles was examined. Ebselen inhibited K(+)-dependent ATPase
      activity (IC50 = 0.06 mumol/l), phosphoenzyme formation (IC50 = 0.25 mumol/l),
      and K(+)-dependent p-nitrophenylphosphatase activity (IC50 = 0.09 mumol/l:
      dephosphorylation step of this enzyme). Furthermore, this compound prevented
      changes in the fluorescence intensity of flourescein isothiocyanate-labeled
      enzyme (E1-->E2K form, IC50 = 0.33 mumol/l). Pretreatment with 2 mmol/l of
      dithiothreitol (DTT) used as a sulfhydryl compound completely protected against
      these inhibitory effects. These findings indicate that ebselen-induced
      inactivation of gastric H+,K(+)-ATPase may result from prevention of the partial
      reaction steps, which include phosphorylation, dephosphorylation and
      conformational change (E1-->E2K form), through interference with sulfhydryl
      groups of the enzyme.

PMID- 8135880
TI  - Effect of actarit on type II collagen-induced arthritis in mice.
AB  - The effect of actarit (MS-932, CAS 18699-02-0), an antirheumatic drug, on type II
      collagen (CII)-induced arthritis in DBA/1J mice was studied. Mice were immunized
      twice with bovine CII, actarit being given orally once a day for 35 days after
      the 1st immunization. Clinical assessment showed that actarit had no effect on
      the incidence or day of onset of arthritis but that it lowered the arthritis
      score dose-dependently. Radiography showed that actarit reduced new bone
      formation in the limbs, and a histopathologic examination showed that it reduced
      synovitis, erosion of cartilage and bone destruction. Actarit suppressed the
      delayed-type mouse ear skin reaction to CII but had no effect on the level of
      serum anti-CII antibodies. These results suggest that actarit inhibits the
      development of CII-induced arthritis in mice by suppressing delayed-type
      hypersensitivity to CII.

PMID- 8135881
TI  - Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the
      knee. A randomised, placebo-controlled, double-blind study.
AB  - Glucosamine sulfate (Dona, CAS 29031-19-4) is a drug used in the treatment of
      osteoarthritis. When orally given, it is more effective than placebo and at least
      as effective as non-steroidal anti-inflammatory drugs in relieving osteoarthritis
      symptoms. The aim of this multicentre, randomised, placebo-controlled, double
      blind, parallel-group study was to assess the efficacy and safety of glucosamine
      sulfate intramuscularly given on the same parameters. 155 out-patients with knee
      osteoarthritis (Lequesne's criteria), radiological stage between I and III,
      Lequesne's severity index of at least 4 points and symptoms for at least 6
      months, were treated with i.m. glucosamine sulfate (or placebo) 400 mg twice a
      week for 6 weeks. Clinic visits were performed at enrollment, after a 2-week
      baseline, at weekly intervals during treatment and 2 weeks after drug
      discontinuation. Responders to treatment were considered those patients with a
      reduction of at least 3 points in the Lequesne index, together with a positive
      overall judgement by the investigator. The Lequesne index was slightly over 10
      points in average in both groups at the beginning of treatment. A significant
      decrease in the index was observed for glucosamine compared to placebo (3.3 vs.
      2.0 points in average, respectively; p < 0.05, Student's t-test). The responder
      rate in the evaluable patients was 55% with glucosamine (n = 73) and only 33% (n
      = 69) with placebo (p = 0.012, Fisher's Exact Test). According to the intention
      to-treat approach, considering also drop-outs, these proportions were 51% vs. 30%
      (p = 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135882
TI  - Photolability evaluation of the new cytostatic drug mitonafide.
AB  - A qualitative and quantitative study on the stability of the new cytostatic drug
      mitonafide (N-[2-(dimethyl-amino) ethyl]-3-nitronaphthalimide, CAS 54824-17-8)
      against UVA, UVC and visible radiations was carried out. Initially a test with
      controlled lighting on samples from mitonafide solution is carried out. This test
      include the determination of the protector effect of different kinds of glasses
      (clear and amber glass). The results achieved are verified by means of a test in
      normal lighting conditions (direct sun light, normal laboratory lighting and
      darkness). High mitonafide photodecomposition, deeper against UVA radiation,
      requires conservation of raw material in darkness. Similarly UV sterilizing
      radiations must be avoided in sterile rooms during manufacture. The use of amber
      glass ampoules is not enough to protect parenteral solutions from radiations.
      Direct sunlight must be avoided in the manufacture, control tests and
      administration in perfusion of pharmaceutical dosage forms, although artificial
      light can be used during short periods of time.

PMID- 8135883
TI  - Direct detection of the intracellular formation of carboxyphosphamides using
      nuclear magnetic resonance spectroscopy.
AB  - 31P nuclear magnetic resonance (NMR) spectroscopy was used in conjunction with
      cell perfusion techniques to monitor the intracellular chemistry of the
      cyclophosphamide (CP, CAS 6055-19-2) metabolites 4-hydroxy-cyclophosphamide (4-HO
      CP) and aldophosphamide (AP) in U937 human histiocytic (CP-sensitive) and K562
      human erythroleukemia (CP-resistant) cells. Similar experiments were carried out
      using the ifosfamide (IF, CAS3778-73-2) metabolites 4-hydroxyifosfamide (4-HO-IF)
      and aldoifosfamide (AIF). The hydroxy and aldehydic metabolites were generated by
      the triphenylphosphine reduction of 4-hydroperoxycyclophosphamide (4-HO2-CP) or 4
      hydroperoxyifosfamide (4-HO2-IF) or by a spontaneous elimination/addition
      reaction involving water and 4-thiocyclophosphamide analogs 4-(2-hydroxyethyl)
      thiocyclophosphamide (4-ESCP) or mafosfamide. Cell death resulting from 4-HO
      CP/AP perfusions was mimicked by perfusion with acrolein or an acrolein producing
      but non-alkylating, dechloro-CP analog. Acrolein toxicity was minimized by the
      presence of 2-mercaptoethanol or mesna (sodium 2-mercaptoethanesulfonate) in
      perfusion solutions as well as by fractional dose drug perfusions (sequential 2.5
      3.0 h perfusions separated by cell washes with drug-free medium). The
      intracellular half-life for phosphoramide mustard (PM) at an intracellular pH
      value of 7.1 +/- 0.1 and an ambient probe temperature of 23 +/- 1 degree C in
      U937 cells was 2.1 h [k = (5.4 +/- 0.3) x 10(-3) min-1] and in K562 cells was 3.1
      h [k = (3.7 +/- 0.4) x 10(-3) min-1]. Similar half-lives (2-4 h) were determined
      for intracellular isophosphoramide mustard (IPM). Fractional dose perfusion of
      U937 or K562 cells with 1.5 mmol/l 4-HO-CP/AP (generated from 4-HO2-CP) and 0.3
      mmol/l mesna allowed for the observation of intracellular carboxyphosphamide
      (CBP); CBP was formed in higher concentrations in the CP-resistant K562 cells.
      Similar results were obtained using 4-ESCP and mafosfamide as sources of 4-HO
      CP/AP. Identification of CBP was based on chemical shift, chemical stability, and
      membrane permeability studies of synthetic CBP. Concentrations of
      carboxyifosfamide (CBIF) formed in K562 cells were also greater than that in U937
      cells.

PMID- 8135884
TI  - Effect of praziquantel treatment on lipid peroxide levels and superoxide
      dismutase activity in tissues of healthy and Schistosoma mansoni infected mice.
AB  - The elevated levels of lipid peroxide product as malondialdehyde (MDA) in plasma,
      liver, spleen, intestine and kidney of Schistosome-infected mice were differently
      ameliorated by treatment with praziquantel (EMBAY 8440, CAS 55268-74-1) (2 x 500
      mg/kg body wt.) being nearly normalized in plasma and intestine, moderately
      improved in liver and slightly affected in spleen and kidney. However, the drug
      failed to affect the MDA levels in the different organs of healthy mice.
      Moreover, the increased hepatic superoxide dismutase (SOD) activity in infected
      mice was normalized while the decreased activities in the other tissues were
      further decreased than normal values in response to praziquantel treatment.
      Interestingly, in healthy mice, the drug similarly inhibited SOD activities in
      blood, spleen and kidney. The specificity of this action remains to be clarified.
      Possible explanations of these findings are given.

PMID- 8135885
TI  - Change-to-Open-Label Design. Proposal and discussion of a new design for clinical
      parallel-group double-masked trials.
AB  - The "Change-to-Open-Label Design" (COLA-design) is proposed to overcome some of
      the ethical and organizational problems of the usual double-masked design in
      certain situations while preserving its scientific rigor. Patients are randomized
      on a doubled-masked basis into treatment groups. During the trial the patient or
      the treating physician may ask for a change from the masked treatment to any open
      label treatment of their choice (experimental or not), if the masked treatment is
      thought to be unsatisfactory. It seems to be easier to obtain a patient's
      informed consent to participate in placebo controlled double-masked trials
      especially for long term studies. The main outcome variable in COLA-design is the
      time until a patient demands for such a change. "Survival analysis" is a powerful
      statistical method to evaluate this outcome variable. Even patients lost from
      observation can be included in the evaluation: they still deliver censored
      outcome values. Evidently, in trials with a COLA-design the patient's personal
      impression of the therapy is the most important factor in its assessment.
      Therapeutical success is mingled with undesirable effects into the outcome
      measure; therefore this design is especially applicable to investigate treatments
      supposed to increase quality of life.

PMID- 8135886
TI  - What communication disorders do experienced clinicians prefer to manage?

PMID- 8135887
TI  - Developing a model program in speech-language pathology and audiology for the
      inner-city university. Capitalizing on our assets.

PMID- 8135888
TI  - ASHA interviews Jeri A. Logemann 1994 president.

PMID- 8135889
TI  - Audiology's journey from the red "o's" and blue "x's".

PMID- 8135890
TI  - An inevitable fact of life.

PMID- 8135891
TI  - In and out of hot water: women in academic administration.

PMID- 8135892
TI  - Graduate student preparation: tomorrow's challenge.

PMID- 8135893
TI  - Are we ready for the 21st century?

PMID- 8135894
TI  - Self-management in a changing profession: shoring up our hardiness for change.

PMID- 8135895
TI  - A plan for specialty recognition. Ad Hoc Committee on Specialty Recognition.

PMID- 8135896
TI  - The protection of rights of people receiving audiology or speech-language
      pathology services. Task Force on Protection of Clients' Rights.

PMID- 8135897
TI  - Training technicians.

PMID- 8135898
TI  - Health reforms.

PMID- 8135899
TI  - Academic medicine: plenty of room at the top.

PMID- 8135900
TI  - Arthritis mistaken for injury.

PMID- 8135901
TI  - Successful treatment of visceral leishmaniasis with allopurinol plus ketoconazole
      in a renal transplant recipient after the occurrence of pancreatitis due to
      stibogluconate.
AB  - A case of a renal transplant recipient who developed pancreatitis during
      stibogluconate treatment for visceral leishmaniasis and who was successfully
      treated with a combination of allopurinol and ketoconazole is reported. The
      features of this case are compared with those of the three previously reported
      cases of pancreatitis during stibogluconate treatment. Complete cure was achieved
      during the follow-up period of 15 months. If stibogluconate is used for treatment
      of renal transplant recipients, we advise extreme caution with close observation
      and combination therapy to be considered instead.

PMID- 8135902
TI  - Academic medicine.

PMID- 8135903
TI  - Mohs surgery explained.

PMID- 8135904
TI  - Endocarditis following skin procedures.
AB  - Four cases of infective endocarditis following skin procedures are reported.
      Three of these patients had known cardiac valve abnormalities. None received
      antibiotic prophylaxis and three of the patients died. Prophylaxis should be
      considered for patients with known cardiac abnormalities before skin procedures
      are undertaken.

PMID- 8135905
TI  - An interview with the president.

PMID- 8135906
TI  - Testicular fine needle aspiration as a diagnostic method.
AB  - We believe testicular FNA is a reliable, simple, and accurate method for the
      assessment of testicular pathology and can replace the biopsy. Only when
      insufficient conclusions may be drawn from the cytologic smears obtained is open
      biopsy indicated.

PMID- 8135907
TI  - Appraisal and junior medical staff.

PMID- 8135908
TI  - Second opinions for patients recommended for coronary angiography.

PMID- 8135909
TI  - Metastatic mature teratoma in lung following testicular embryonal carcinoma and
      teratocarcinoma.
AB  - We report seven cases of metastatic mature teratoma in the lung from testicular
      teratocarcinoma and embryonal carcinoma. The patients were between 19 and 58
      years of age when orchiectomy was performed. The primary tumors each contained a
      prominent component of embryonal carcinoma as well as mature and immature
      teratoma in six patients and only embryonal carcinoma in one. In three patients
      metastatic pulmonary nodules were detected at the time of orchiectomy, and in
      three others pulmonary metastases occurred 4 and 8 months after orchiectomy. In
      one patient the interval was 1.5 years; however, chest roentgenography was not
      performed during that period. All the patients received chemotherapy or radiation
      therapy prior to removal of the pulmonary metastases. Thoracotomy was performed
      between 4 months and 9 years after detection of pulmonary metastases on chest
      roentgenograms. In one patient the procedure consisted of a lobectomy and in
      another a pneumonectomy. In the remaining five cases excision of the nodules was
      performed. The pulmonary metastases resected were grossly solitary lesions in
      five patients and multifocal in two. Microscopically, each tumor consisted
      entirely of mature teratoma. Cuboidal and mucin-secreting glandular epithelium
      predominated in the cystic areas; fibroconnective tissue was the predominant
      feature of the solid areas. In four patients the course has been indolent with no
      manifestations of the disease after at least 1 year; in two patients no follow-up
      was obtained; and one patient died, apparently of a septic process. We present a
      discussion of this interesting and unusual event.

PMID- 8135910
TI  - Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.
AB  - BACKGROUND: Open lung biopsy is often performed to confirm the diagnosis in
      patients with suspected fibrosing alveolitis. The superior sensitivity and
      specificity of high resolution computed tomography (CT) over chest radiography in
      various diffuse lung diseases suggest that the characteristic appearance of
      fibrosing alveolitis on high resolution CT might render biopsy confirmation
      unnecessary. METHODS: The chest radiographs and high resolution CT scans of 86
      patients (41 with fibrosing alveolitis and 45 with various other diffuse lung
      diseases) were examined individually and independently by two observers. No
      clinical information was given and the observers gave a level of confidence when
      the diagnosis was thought to be fibrosing alveolitis. RESULTS: The observers
      correctly and confidently discriminated between fibrosing alveolitis and other
      diffuse lung diseases on high resolution CT with an accuracy of 88% and on chest
      radiography with an accuracy of 76%. The false negative rate for fibrosing
      alveolitis diminished from 29% on chest radiography to 11% on high resolution CT.
      The false positive rate on chest radiography was 19% and on high resolution CT
      13%; the false positive diagnoses on CT were the result of a few conditions
      (extrinsic allergic alveolitis, sarcoidosis, cryptogenic organising pneumonia,
      and pulmonary eosinophilia) which mimicked some of the CT features of fibrosing
      alveolitis. The superficial similarity of the CT patterns of these conditions are
      discussed. CONCLUSIONS: High resolution CT is superior to chest radiography in
      establishing the diagnosis of fibrosing alveolitis and the typical CT appearances
      are virtually pathognomonic. The diagnostic advantages of CT over chest
      radiography should further reduce the need for open lung biopsy in this
      condition.

PMID- 8135911
TI  - Ankle joint dorsiflexion. Establishment of a normal range.
AB  - Various values have been proposed as the required amount of ankle joint
      dorsiflexion, but a normal range has not been established. The authors establish
      a normal range based on direct measurements and compare the standard
      nonweightbearing method of measuring ankle joint dorsiflexion with a
      weightbearing method. The normal range for ankle joint dorsiflexion was
      established as 0 degrees to 16.5 degrees nonweightbearing and 7.1 degrees to 34.7
      degrees weightbearing. A statistically significant (p < 0.01) difference exists
      between the two measuring systems. In addition, the study shows poor correlation
      between the two measurements. This lack of correlation brings into question the
      clinical relevance of the standard nonweightbearing measurement.

PMID- 8135912
TI  - Blood pressure measurements and intravenous infusions.

PMID- 8135913
TI  - Midwives' Journal. A cause for concern.

PMID- 8135914
TI  - Stress, health and disease.

PMID- 8135915
TI  - Nosocomial outbreak of Klebsiella infection resistant to late-generation
      cephalosporins.
AB  - OBJECTIVE: To describe the epidemiology, antimicrobial susceptibility, and
      control of widespread ceftazidime-resistant Klebsiella pneumoniae infections in a
      North American hospital and circumstances that led to delayed detection. DESIGN:
      A 2-year epidemiologic, microbiologic, and clinical cohort study. SETTING: A 487
      bed general hospital in New York City. PATIENTS AND CLINICAL ISOLATES: Patient
      records were reviewed retrospectively and prospectively. Isolates were obtained
      from the Clinical Microbiology Laboratory. RESULTS: Four hundred thirty-two
      isolates of ceftazidime-resistant Klebsiella pneumoniae were recovered during a
      19-month study period. The peak incidence reached 17.3% of all Klebsiella
      isolates. One hundred fifty-five patients were colonized or infected,
      representing more than 70 per 1000 average daily census. Infections occurred in
      39% of patients from whom ceftazidime-resistant Klebsiella was isolated. These
      included 14 bacteremias and 17 pulmonary infections among 52 infected patients.
      The outbreak coincided with increasing use of ceftazidime therapy for
      multiresistant Acinetobacter infections. Reduction in ceftazidime use and barrier
      precautions markedly reduced the incidence of colonization and infection.
      Ceftriaxone, ceftizoxime, cefotaxime, and cephamycins were inhibitory, but not
      bactericidal, against ceftazidime-resistant Klebsiella and appeared effective by
      routine disc diffusion tests. In contrast, imipenem provided consistent
      bactericidal activity. Preliminary studies indicated that the outbreak was caused
      by one or more plasmid-mediated beta lactamases. CONCLUSIONS: Nosocomial
      ceftazidime-resistant Klebsiella pneumoniae may be resistant to the bactericidal
      activity of all cephalosporins and cephamycins. Such isolates appear susceptible
      to cephalosporins other than ceftazidime by routine disc diffusion testing.
      Ineffective therapy, delayed detection of resistance, and epidemic spread are
      potential consequences. Imipenem provides consistent bactericidal activity.
      Ceftazidime restriction and barrier precautions for colonized and infected
      patients are effective control measures.

PMID- 8135916
TI  - Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the
      kidney.
AB  - We describe a malignant lymphoma arising in the kidney that exhibited clinical
      and histologic features of low-grade B-cell lymphoma of mucosa-associated
      lymphoid tissue (MALT). Clinically, the neoplasm involved the kidney and one
      perirenal lymph node (stage IIE) and did not recur or disseminate following
      nephrectomy, lymphadenectomy, and local radiation therapy. Histologically, the
      neoplasm recapitulated the features of low-grade B-cell lymphomas of MALT at
      other sites. The neoplastic cells resembled centrocyte-like cells, some of which
      formed lymphoepithelial lesions with renal tubules, and reactive lymphoid
      follicles were scattered within the neoplasm. The neoplastic cells expressed
      monotypic cytoplasmic Ig kappa. Low-grade B-cell MALT lymphomas arising in the
      kidney are rare. Their occurrence further demonstrates the diversity of
      anatomical sites that may be involved by MALT lymphomas. In addition, this
      neoplasm also had histologic and cytologic features resembling those of
      monocytoid B-cell lymphoma, supporting the hypothesis that low-grade B-cell
      lymphomas of MALT and monocytoid B-cell lymphomas are closely related and may be
      two morphological manifestations of the same neoplasm.

PMID- 8135917
TI  - Effect of laboratory variation in the prothrombin-time ratio on the results of
      oral anticoagulant therapy.
AB  - BACKGROUND: Patients receiving long-term anticoagulant therapy may be subject to
      unnecessary risks of bleeding or thromboembolism because of variability in the
      commercial thromboplastins used to determine prothrombin time and consequent
      uncertainty about the actual intensity of anticoagulation. METHODS: We explored
      the effect of this uncertainty on the benefits and risks of anticoagulation in
      patients with prosthetic heart valves, using models of thromboembolic and
      hemorrhagic complications as a function of the intensity of anticoagulation, with
      quality-adjusted life expectancy and average variable costs used to describe
      outcomes. RESULTS: Anticoagulation provides a striking benefit for patients whose
      treatment is conducted within the recommended range of the international
      normalized ratio (INR)--i.e., 2.5 to 3.5--but if uncertainty about the laboratory
      results causes the intensity of anticoagulation to fall outside this range, the
      gain becomes smaller. Uncertainty about the true intensity of anticoagulation may
      reduce the potential gain in life expectancy, adjusted for quality of life, by
      more than half and may increase the ratio of costs to effectiveness to almost
      five times the optimal value. Variability in the intensity of anticoagulation is
      even greater if older recommendations advocating a higher level of
      anticoagulation are followed. CONCLUSIONS: Uncertainty about the sensitivities of
      the commercially available thromboplastins used in the United States can have
      important clinical and economic effects. This problem could be eliminated if
      clinical laboratories uniformly reported the intensity of anticoagulation as the
      INR, by adjusting prothrombin-time ratios for variability in thromboplastins.

PMID- 8135918
TI  - Plasma and urinary oestrogens in breast cancer patients on treatment with 4
      hydroxyandrostenedione.
AB  - Plasma and urinary oestrogens were measured in nine breast cancer patients (eight
      postmenopausal women and one man) before and during treatment with the aromatase
      inhibitor 4-hydroxyandrostenedione. Urinary oestrogens were measured by using a
      highly specific GC-MS method. Plasma levels of oestrone, oestradiol and oestrone
      sulphate were suppressed by 66.6% (+/- 3.6%), 57.7% (+/- 5.1%) and 51.8% (+/-
      6.4%) respectively (P < 0.005 for all). Twenty-four hour urinary excretion of
      total oestrogens, oestradiol, oestriol, 2-hydroxyoestrone, 16 alpha
      hydroxyoestrone and the minor metabolites 16 beta- and 15 alpha-hydroxyoestrone
      were all suppressed by mean values ranging from 60% to 82%, (oestradiol: P <
      0.025, otherwise P < 0.005). There were no significant changes in the ratios
      between the different plasma oestrogens. The finding of sustained plasma and
      urinary oestrogens at 20-40% compared to their control levels indirectly support
      a hypothesis of alternative oestrogen sources in postmenopausal breast cancer
      patients on treatment with 4-hydroxyandrostenedione.

PMID- 8135919
TI  - Megakaryocytic and erythrocytic cell lines share a common precursor cell.
AB  - Several recent studies show that production of platelets and red blood cells
      (RBC) are inversely related. For example, it is well established that hypoxia, a
      stimulator of erythropoiesis, causes thrombocytopenia in laboratory animals. The
      thrombocytopenia is most likely the result of a reduction in the production of
      platelets caused by a decrease in the number of colony-forming units
      megakaryocyte (CFU-Meg), early precursor megakaryocytes (small
      acetylcholinesterase-positive cells, SAChE+), and recognizable megakaryocytes in
      the bone marrow. In all cases, active erythropoiesis was required for the
      thrombocytopenia. The hypoxia-induced thrombocytopenia was not caused by
      sequestration of platelets in an enlarged spleen or by expanding blood volumes.
      We speculate that this thrombocytopenia is caused by competition of a precursor
      cell of the erythrocytic and megakaryocytic cell lines; that is, marked
      stimulation of the erythroid cells by erythropoietin (Epo) causes a decrease in
      the number of immature megakaryocytes, leading to decreased thrombocytopoiesis.
      In support of this hypothesis, other recent work shows that thyroxine (a
      stimulator of erythropoiesis) and Epo (when given in large, chronic doses)
      elevate erythropoiesis and cause thrombocytopenia. Conversely, both endogenous
      and exogenous sources of thrombopoietin lead to elevated thrombocytopoiesis and
      anemia in mice. It should also be mentioned that megakaryocytes and erythrocytes
      have several biochemical similarities, and several clinical conditions point to
      an inverse relationship between RBC and platelet production. These in vivo,
      biochemical, and clinical data support the hypothesis that megakaryocytes and
      erythrocytes share a common precursor cell.

PMID- 8135920
TI  - Safe right subclavian vein puncture: the importance of pressing the skin with the
      left thumb.

PMID- 8135921
TI  - Tough decisions.

PMID- 8135922
TI  - The fiscal impact of the Medicaid abortion funding ban in Michigan.
AB  - OBJECTIVE: To assess the increased public assistance costs resulting from
      Michigan's 1988 ban on Medicaid funding of abortions. METHODS: The increased
      number of births resulting from the Medicaid abortion funding ban was estimated.
      The costs of this increase in births to the state and federal governments were
      then calculated. RESULTS: Using low and high estimates for the numbers of
      additional children born as a result of Michigan's prohibition of Medicaid
      abortion funding (2120 and 5800), and the likelihood of these children's
      remaining on welfare, the 1991 cohort of infants will cost the state's taxpayers
      $23.1-63.2 million--several times the $6-7 million cost of the abortions, had
      they taken place. Including the federally paid share, total incremental costs are
      $50.2-137.4 million. CONCLUSION: Those who have advocated banning Medicaid
      funding of abortions to reduce government spending, as in Michigan in 1988, have
      ignored the much greater cost of requiring that those pregnancies be carried to
      term.

PMID- 8135923
TI  - The attractiveness of internal medicine: a qualitative analysis of the
      experiences of female and male medical students. Society of General Internal
      Medicine Task Force on Career Choice in Internal Medicine.
AB  - OBJECTIVE: To understand better the decline in medical student interest in
      internal medicine. DESIGN: Qualitative analysis of 500 essays from respondents
      who participated in a national survey of graduating medical students from the
      class of 1990 in 16 medical schools. Medical students were asked the open-ended
      question, "What suggestions do you have for improving the attractiveness of
      internal medicine?" A model of career choice was developed for the analysis that
      included the following factors: ambulatory care exposure and primary care
      (including relationships with patients); attending physician-student interactions
      and learning climate; stress and workload; income and prestige; and intellectual
      stimulation. PARTICIPANTS: The original survey included 1650 fourth-year medical
      students; 500 essay respondents were stratified by sex and then randomly chosen
      for the analysis. RESULTS: Students most frequently suggested that ambulatory
      care experiences be increased and that better relationships with patients be
      established during medical training (65% of women and 50% of men, P < 0.01). The
      second most frequent suggestion was to improve internal medicine attending
      physicians' interactions with students (51% and 48% of women and men,
      respectively). Students who had seriously considered a career in medicine but
      switched to other primary care careers (general pediatrics, family medicine) had
      few concerns about income and prestige, whereas those who chose internal medicine
      had reservations about expected workload and income. Women were more likely than
      men to reject internal medicine for other primary care fields (26% of women
      compared with 16% of men, P = 0.05). CONCLUSIONS: Students, particularly female
      students, expressed a strong interest in establishing better relationships with
      patients. Lack of respect by medical attendings and negative teaching methods
      were important sources of dissatisfaction among both men and women. Attention to
      these relationship issues, in addition to housestaff stress and expected future
      income, may improve the attractiveness of internal medicine.

PMID- 8135924
TI  - Aminopeptidase P: immunoaffinity purification and molecular characterisation.

PMID- 8135925
TI  - Stabilisation of a bent conformation in a neurokinin A analogue by an a,a-dialkyl
      amino acid.

PMID- 8135926
TI  - Transcription factor interactions in human lung.

PMID- 8135927
TI  - Qualitative and quantitative changes in glutathione S-transferases in the
      mosquito Anopheles gambiae confer DDT-resistance.

PMID- 8135928
TI  - Molecular recognition in insulin assembly.

PMID- 8135929
TI  - The induction of cellular interactions in atherogenesis and their modulation.

PMID- 8135930
TI  - Pyruvate formate-lyase mechanism involving the protein-based glycyl radical.

PMID- 8135931
TI  - The regulation of oxidative phosphorylation in plant mitochondria: the roles of
      the quinone-oxidizing and -reducing pathways.

PMID- 8135932
TI  - Chronic mitral valve disease in cavalier King Charles spaniels: 95 cases (1987
      1991)
AB  - Systolic heart murmurs caused by chronic mitral valve disease are particularly
      common in Cavalier King Charles Spaniels (CKCS) in Great Britain. To determine if
      American-bred CKCS have a similar high prevalence of chronic valve disease,
      results of stethoscopic examinations on 394 CKCS were analyzed. Left apical
      systolic heart murmurs were found in 22% of the dogs. The prevalence ranged from
      9% in dogs < 1 year old to 100% in those > or = 10 years old; prevalence was 56%
      in dogs > or = 4 years old. Differences were not found in prevalence between
      sexes and among various coat colors. Reexamination of 79 dogs after 1 year
      revealed an incidence of new murmurs of 21%. Comparison of ages at initial
      examination in 128 referral hospital cases with chronic mitral valve disease
      revealed a mean age of 6.25 years in 17 CKCS, in contrast to a mean age of 12
      years in other breeds. Echocardiographic and necropsy findings indicated that
      ruptured chordae tendineae and mitral valve prolapse are major components in the
      chronic valve disease process in CKCS.

PMID- 8135933
TI  - Fully informed consent can be needlessly cruel.

PMID- 8135934
TI  - Toluene diisocyanate induced asthma: outcome according to persistence or
      cessation of exposure.

PMID- 8135935
TI  - Psychiatric consequences of road traffic accidents. Loss of memory is protective.

PMID- 8135936
TI  - Anticoagulation in patients with atrial fibrillation. GPs not prepared for
      monitoring anticoagulation.

PMID- 8135937
TI  - Anticoagulation in patients with atrial fibrillation. Doctors reluctant despite
      evidence.

PMID- 8135938
TI  - Informed consent in clinical trials. Raise public awareness...

PMID- 8135939
TI  - Sagittal abdominal diameter.

PMID- 8135940
TI  - Clinical and pathological spectrum of coeliac disease.

PMID- 8135941
TI  - Blood transfusion does not have an adverse effect on survival after operation for
      colorectal cancer.

PMID- 8135942
TI  - Necrotizing retinitis and cerebral vasculitis due to varicella-zoster virus in
      patients infected with the human immunodeficiency virus.

PMID- 8135943
TI  - Pluronic-F68 and venous gas emboli.

PMID- 8135944
TI  - Unrecognized adverse drug reactions.

PMID- 8135945
TI  - Early failure of short-segment pedicle instrumentation for thoracolumbar
      fractures. A preliminary report.

PMID- 8135946
TI  - Ankle dorsiflexion.

PMID- 8135947
TI  - Warfarin and aspirin after heart-valve replacement.

PMID- 8135948
TI  - Clinical problem-solving: prevention of meningococcal infection.

PMID- 8135949
TI  - Creative part-time faculty arrangements.

PMID- 8135950
TI  - [Incidental occurrence of Lewy bodies in the brains of elderly patients--the
      relevance to aging and Parkinson's disease].
AB  - The Lewy body (LB) is a cytoplasmic neuronal inclusion that is constantly found
      in the substantia nigra and locus ceruleus, and other specific brain regions in
      Parkinson's disease (PD). In the present study, the significance of non
      parkinsonian cases in which the LBs were an incidental finding was investigated.
      In 1,452 autopsy series (age range, 1-89 years), 27 incidental cases of LBs and
      21 patients with PD were found. The age-specific prevalence of incidental LBs
      steadily increased from 0.7% to 6.5% between the sixth and ninth decades. The
      distribution of LBs in incidental cases was similar to that in PD. The number of
      neurons in the substantia nigra and locus ceruleus was determined in 8 incidental
      cases (age range, 60-81 years), 9 patients with PD (range, 56-81 years) and 9
      control subjects (range, 60-81 years). In incidental cases, the average numbers
      of pigmented neurons in the substantia nigra and locus ceruleus was 83% and 77%
      of those in control subjects, respectively. In PD, the average numbers of
      pigmented neurons in the substantia nigra and locus ceruleus was 28% and 19%
      those of controls, respectively. However, the number of nonpigmented neurons in
      the substantia nigra was not reduced in incidental cases and PD. From the above
      findings, it is suggested that there exists a close relationship between the
      occurrence of LBs and aging. However, in the brains of elderly patients,
      incidental LBs were considered to be pathological findings rather than simple
      aging phenomenon. Therefore, it has been suggested that incidental cases may
      represent early and presymptomatic cases of PD.

PMID- 8135951
TI  - Bimanual motor performance in controls and patients.

PMID- 8135953
TI  - Smallpox virus stocks: more votes.

PMID- 8135952
TI  - Normalization of uremic acidosis in hemodialysis patients with a high bicarbonate
      dialysate.

PMID- 8135954
TI  - Ceftazidime-resistant Klebsiella.

PMID- 8135955
TI  - More on stability of albumin, N-acetylglucosaminidase, and creatinine in urine
      samples.

PMID- 8135956
TI  - Sex and longevity.

PMID- 8135957
TI  - Research in multiple personality disorder.

PMID- 8135958
TI  - Evaluation of Spanish research.

PMID- 8135959
TI  - Distal limb anomalies, Robin sequence, and deletions in 4q31-->qter.

PMID- 8135960
TI  - Comments on study of coxofemoral joint laxity.

PMID- 8135961
TI  - Positive end-expiratory pressure and shunting across foramen ovale.

PMID- 8135962
TI  - Comments on poison control centers.

PMID- 8135963
TI  - Screening for cephalosporin-resistant Streptococcus pneumoniae with the Kirby
      Bauer disk susceptibility test.

PMID- 8135964
TI  - Breech delivery at term: a critical review of the literature.

PMID- 8135965
TI  - It's report card time again.
AB  - The author, the outgoing president of the AAMC, presents report cards on how the
      academic medicine enterprise is faring today and how it may fare in the year 2000
      by assigning grades to four spheres of activity: Manpower gets a D today, for the
      following reasons: (1) There are still far too many specialists and too few
      primary care physicians, and the problem may be worsening; (2) the proportion of
      underrepresented minorities is still too low in medical schools and the physician
      workforce, but there are encouraging signs that this problem may be lessening,
      thanks to schools' efforts to fulfill the mandate of the AAMC's Project 3000 by
      2000; (3) student indebtedness is increasing, a situation that affects some
      students' choices of specialties. By the year 2000, the grade for manpower will
      rise to a C, since most Americans will have access to care, and there will be
      some--but not dramatic--improvement in the generalist-specialist balance.
      Effectiveness of medical school faculties gets a C today, mainly because although
      faculties have grown with no corresponding increase in students, there has been
      no significant increase in time or effort devoted to teaching. By the year 2000,
      the faculty grade will rise to a B, since the faculty will be leaner and may
      teach better, tenure will have become rare, especially in clinical departments,
      and faculty practice activities will not usurp academic activities to the extent
      they do today. Research gets a B+ today for solid accomplishments in the face of
      major constraints.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135966
TI  - How targeted should research and higher education be?
AB  - The education and research system in the biomedical sciences is tremendously
      vital. But the scientific community must exert more leadership if this vitality
      is to continue, for both science education and research are prone to a common
      villain: inertia. For example, in the education arena, why do medical schools
      require two semesters of organic chemistry but no cell biology, when the center
      of biomedical research has shifted to cell biology? And why do so many graduate
      schools continue to send a strong message to their science students that there is
      only one really successful career path--the one leading to academia--when most of
      our PhD students cannot expect to become professors? Inertia in research can be
      seen in the trend for cell biologists to train researchers just like themselves,
      which means that the many opportunities to use new cell biological techniques to
      address important problems in tissue biology are likely to be missed. A solution
      to such problems is to design funding mechanisms that promote more adventuresome
      research. As a bottom line, our research system must support the independence of
      our best young scientists and encourage them to take the risks inherent in highly
      creative endeavors.

PMID- 8135967
TI  - Academic medicine's choices in an era of reform.
AB  - Academic medicine is once more face-to-face with health care reform, which this
      time is being seriously debated and will at least be the subject of legislation.
      There is the possibility that the coming changes could unintentionally injure
      academic medicine; that is why academic medicine's leaders must be participants
      and constructive contributors to the discussion rather than simply being critics.
      The author describes the economic, social, and educational forces that have led
      to the present reform proposals, indicates the main proposals that are being made
      to respond to these forces, and states ways that academic medicine can
      effectively change to meet the coming reforms. For example, curriculum content
      can change (e.g., revise courses to strengthen the bridge between the basic and
      clinical sciences); there can be more public health emphasis; the educational
      structure can change (e.g., continue to modify the sites for clinical education);
      and academic medicine's philosophy can change (e.g., broadening the acute-care,
      biologically-based medical approach). The author also discusses risks of the
      proposed reforms to academic medicine (e.g., stagnant support of basic research;
      political pressures for the distribution of resources for prevention services
      research and other reforms; decrease in the support available for hospitals'
      examination of clinical activities), and emphasizes that academic medicine's
      traditional inertia is one of the greatest risks in the coming years. In
      conclusion, the author proposes that the university become the base of the
      medical school and that the health system become the base of the university
      hospital; an interactive federated relationship between medical schools and
      hospitals will allow academic medicine to stay flexible enough to effectively
      meet the coming changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8135968
TI  - Doctoring: a longitudinal generalist curriculum.
AB  - It is clear that no matter what type of national health care reform is adopted,
      there will be a shift in the care that physicians are asked to provide: from high
      tech to patient-centered, from cost-indifferent to cost-conscious, from treatment
      focused to prevention-focused. It is critical that physicians be adequately
      trained to meet these new challenges. The medical education community needs to
      search for innovative, creative approaches to help our students develop the
      knowledge, skills, and attitudes needed to practice medicine in the next century.
      Doctoring is UCLA's approach to such curriculum reform.

PMID- 8135969
TI  - Coping with innovation frenzy.

PMID- 8135970
TI  - Universal coverage, paying for it, and the months ahead.

PMID- 8135971
TI  - Striking the balance.

PMID- 8135972
TI  - Centralized family practice curricula: the Canadian experience.

PMID- 8135973
TI  - Departments of medicine and teaching hospitals.

PMID- 8135974
TI  - Comprehension formulas for ambulatory care training.

PMID- 8135975
TI  - Computer simulations and management of critical incidents.

PMID- 8135976
TI  - A short course in research ethics for trainees.

PMID- 8135977
TI  - An oath for entering medical students.

PMID- 8135978
TI  - Practicing physical evaluation skills on community volunteers.

PMID- 8135979
TI  - Evaluations of small-group teaching.

PMID- 8135980
TI  - Resident-patient interactions: the humanistic qualities of internal medicine
      residents assessed by patients, attending physicians, program supervisors, and
      nurses.
AB  - BACKGROUND: The patient-physician relationship is central to medical practice.
      Increasingly, educators and certifying bodies seek to assess trainees' humanistic
      qualities. METHOD: The humanistic qualities of first-year internal medicine
      residents were rated in 1987-88 and 1988-89 by patients hospitalized on the
      general internal medicine and pulmonary services of the University of Michigan
      Hospital. Attending physicians (for 1988-89 only), program supervisors (program
      directors and chief residents), and nurses (for 1988-89 only) rated the same
      residents, and these ratings were compared with those of the patients. RESULTS: A
      total of 625 patient questionnaires for 70 residents were analyzed, with a mean
      of nine patient evaluations per resident and a range from four to 24. Analysis
      showed that more than 50 patients would need to rate each resident to achieve
      desired levels of reproducibility. Large numbers of attending physicians (20 to
      50) would also be required to obtain a reproducible assessment; the attending
      physicians' ratings correlated only moderated well (r = .26) with the patients'
      ratings. Ratings from smaller numbers of program supervisors (five to ten) and
      nurses (ten to 20) would be needed for reproducible assessments. However, only
      the nurses' ratings showed a moderately strong relationship (r = .35) with the
      patients' ratings. CONCLUSIONS: Patients, attending physicians, program
      supervisors, and nurses view differently the humanistic attributes of residents
      as they interact with patients. Large numbers of patients and attending
      physicians would be needed to obtain reproducible ratings. Nurses' and program
      supervisors' ratings are much more reproducible, but nurses' perceptions
      correlate more closely to those of patients.

PMID- 8135981
TI  - An integrated health care model in medical education: interviews with faculty and
      administrators.
AB  - PURPOSE: To broaden the understanding of how medical schools can help students
      learn an approach to health care that reflects the integration of psychosocial
      and biomedical factors in health and illness. METHOD: A qualitative research
      design was used, with data collected through document review and semi-structured
      interviews conducted in the spring and summer of 1992 with 22 faculty and
      administrators from 17 U.S. and Canadian medical schools. The interviewees
      represented the following disciplines: internal medicine, family medicine,
      pediatrics, psychiatry, and preventive/behavioral medicine. An analytic framework
      was developed, within which the constant comparative method was used on a
      continuous basis during and after data collection. Category development focused
      on (1) defining the scope and character of an integrated perspective, (2)
      delineating various ways to incorporate such a perspective in medical education,
      and (3) identifying barriers to and facilitative factors for incorporating such a
      perspective in medical education. Validity was assessed by having the
      interviewees and three other faculty members review the analyses and preliminary
      results. RESULTS: The interviewees' conceptions of an integrated perspective on
      health care focused on the theoretical need for a broader scientific model and on
      the practical need for more inclusive approaches to medical practice. The
      interviewees described patient-level and community-level approaches as equally
      important. The ideal curricula envisioned by the interviewees were patient
      centered, integrated, developmental, and population-based. In addition to naming
      many barriers to integration (e.g., negative attitudes of faculty and
      administrators, diffuse organization of medical schools, ignorance of appropriate
      curriculum design and implementation), the interviewees identified certain
      facilitative factors (e.g., strong leaders, faculty development programs, and
      reform of the faculty reward system). CONCLUSION: The interviewees envisioned an
      integrated model of health care that suggests that medical curricula should
      address the development of physicians' knowledge, attitudes, and skills regarding
      physicians' relationships with both patients and community.

PMID- 8135982
TI  - The effect of teaching medical students on private practitioners' workloads.
AB  - BACKGROUND: The costs in time and money of medical student education for family
      physicians in private practice is uncertain, with the literature containing
      conflicting reports. METHOD: Questionnaires were mailed in 1992-93 to 56 primary
      care physicians who had taught third- or fourth-year students during the previous
      academic year in fulfillment of the students' required four-week family medicine
      preceptorships at the University of Missouri-Columbia School of Medicine.
      RESULTS: Forty-six physicians responded. The physicians had been preceptors for
      74 students. Most of the physicians reported increases in time spent at work
      (mean of 46 minutes per day, standard deviation of 32 minutes) when a student was
      present in their practices. Only five noted decreases in billed charges.
      CONCLUSION: The preceptors were consistent in their indications that having
      students in their offices increased their time at work. This suggests that
      teaching medical students places a substantial temporal burden on private
      practitioners.

PMID- 8135983
TI  - Cultural-sensitivity training in U.S. medical schools.
AB  - BACKGROUND: As the United States becomes more multicultural, physicians face the
      challenge of providing culturally sensitive and appropriate health care to
      patients with differing health beliefs and values. While a few schools are
      providing cultural-sensitivity training in response to the changing patient
      population, the pervasiveness of such training has not been thoroughly reported.
      METHOD: In 1991-92, all 126 U.S. medical schools were surveyed regarding their
      implementation and plans for future implementation of cultural-sensitivity
      training. The t-test was used to compare data from those schools that offered
      separate, formal cultural-sensitivity courses with data from the schools that did
      not offer such courses. RESULTS: Of the 126 schools surveyed, 98 (78%) responded.
      Only 13 of the responding schools offered cultural-sensitivity courses to their
      students, and all but one of these courses were optional. These 13 schools
      reported a greater perceived likelihood that their students would have contact
      with African-American patients (t = 2.88, p < .05). Despite the few courses
      offered and the common perception that recent graduates were only "somewhat
      prepared" to provide culturally sensitive clinical services, only 33 schools were
      planning to implement new courses. CONCLUSION: The results indicate needs for
      more cultural-sensitivity training and for further studies to determine the most
      effective type of training for students.

PMID- 8135984
TI  - An innovative course in surgical critical care for second-year medical students.
AB  - PURPOSE: To assess students' learning and other aspects of an innovative elective
      (based on contextual learning) in surgical critical care for second-year medical
      students. METHOD: In 1990-91, 13 second-year students at the University of
      Colorado School of Medicine took a 12-week elective in surgical critical care.
      The elective required the students to be on night call four times in the surgical
      intensive care units of two university-affiliated hospitals, where they were
      supervised by second-year surgical residents and collected information about
      patients. Weekly tutorial sessions were held for case presentations by the
      students and for lectures by attending surgeons on pertinent clinical entities.
      At the conclusion of the course, the students took a shelf test from the Society
      of Critical Care Medicine. RESULTS: All 13 students scored above 70% on the shelf
      test, a passing grade for the Additional Qualifications in Critical Care.
      CONCLUSION: That the students passed an examination at the level of the
      Additional Qualifications in Critical Care without completing a surgical
      residency, let alone a critical care fellowship, suggests that contextual
      learning (where the clinical problem is presented initially and is then followed
      by self-directed study and group discussion) would prove highly effective in
      medical education. Students would enter clinical clerkships more prepared than
      presently if clinical skills were introduced contextually into the basic science
      curriculum.

PMID- 8135985
TI  - Residents' knowledge of the National Practitioner Data Bank.

PMID- 8135986
TI  - Changes in medical students' Myers-Briggs "preferences" between their first and
      fourth years of school.

PMID- 8135987
TI  - The effect of cis-DDP and Pt mercaptopyridine complexes on cell lines in vitro.
AB  - The effect of Platinum (II) complexes with mercaptopyridines on cell lines
      (fibroblasts 3T3 and the tumour ones F10, Fohn, Lovo) were studied. Synthesis and
      characterization of the compounds are reported together with the preliminary in
      vitro tests. Data obtained on cytopathogenic effect (CPE), cell growth and colony
      forming ability demonstrated that all the platinum mercaptopyridines tested are
      more active than cisplatin in the same conditions.

PMID- 8135988
TI  - Synthesis of 9,10-anthraquinone monoalkylaminoalkylhydrazones as potential
      antitumor drugs.
AB  - In the constant search for new compounds endowed with antitumor activity we have
      synthesized a series of anthraquinone hydrazones, which can bee seen either as
      opened-cycle modified anthrapyrazoles or as chromophore-modified
      anthracenediones. Seven 9,10-anthraquinone monoalkylaminoalkylhydrazones (3c-i)
      were synthesized from 10,10-dibromoanthrone (4) and a suitable N-alkylhydrazine.
      The hydrazones were converted into hydrochlorides and tested for their cytotoxic
      activity against L1210 murine leukemia cells. Two of them possess marginal
      activity in vitro.

PMID- 8135989
TI  - Synthesis in solution of oligodeoxynucleotides and some their 5'- and 3'-linked
      derivatives.
AB  - Antisense oligodeoxynucleotides (ODNs) and their derivatives are highly
      interesting tools to regulate gene expression and promising drugs for antiviral
      and anticancer therapy. In view of performing more extensive pharmacological
      trials requiring relatively great amounts of ODNs, we used a method of ODN
      synthesis derived from the phosphotriester approach which allow to prepare ODNs
      covalently linking cholesteryl residue (in 5' or 3') and phenazinium group (in
      5'). HPLC purifications are discussed.

PMID- 8135990
TI  - 1-Aminocyclopropane-1-carboxylic acid derivatives: a new, general synthesis and
      NMDA receptor complex binding affinity study.
AB  - A new synthesis of 1-aminocyclopropane-1-carboxylic acid and of its (E)- and (Z)
      2-substituted analogues (R = CH3;i-Pr;C6H5) has been performed by means of the
      "diazo-addition" method, starting from N-(diphenylmethylene)-2,3-dehydro-1-amino
      1-carboxylate precursors. The (E)- and (Z)-2-phenyl and the (Z)-2
      methylcyclopropaneamino acids have been obtained with high diastereospecificity.
      All the cyclopropaneamino acids prepared were tested for their affinity for some
      glutamate receptors and resulted inactive, with the exception of compounds (E)-1b
      and (Z)-1c which showed a shallow displacement of [3H]-glycine binding.

PMID- 8135991
TI  - Pyrazolo[4,3-c]quinolines, synthesis and specific inhibition of benzodiazepine
      receptor binding. Note II.
AB  - Two new series of 2-arylpyrazolo[4,3-c]quinolin-3-ones (6,8-difluoro- and 7,9
      dichloro-derivatives) have been synthesized and tested for their ability to
      displace [3H]flunitrazepam from rat brain membranes. Several compounds possess
      comparable and sometimes higher affinity for central benzodiazepine receptors
      than that of diazepam. Some selected compounds were also tested in vivo in the
      anti-pentylenetetrazol test; some anticonvulsant activity resulted for the 6,8
      difluoroderivatives only.

PMID- 8135992
TI  - Synthesis and in vitro phototoxicity of 5-(arylmethylene)-1,3,3-trimethyl-2
      oxabicyclo[2.2.2]octan-6-ones, a class of potential sunscreens.
AB  - A series of 5-(arylmethylene)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6- ones
      was prepared by reaction of (+)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one
      with aromatic aldehydes in an alkaline medium. These compounds can be considered
      as potential UVB or UVA sunscreens. In vitro phototoxicity tests (photohemolysis
      and Candida albicans) showed that they exhibit in general a low phototoxicity
      level.

PMID- 8135993
TI  - 3-(Arylamino)-6,7-dihydro-6-methylpyrano[4,3-c]pyrazol-4(1H or 2H)-ones with
      antipyretic, analgesic, antiarrhythmic, hypotensive and other activities.
AB  - The synthesis of 3-(arylamino)-6,7-dihydro-6-methylpyrano[4,3-c]pyrazol-4(1H or
      2H)-ones by reaction of N-aryl-5,6-dihydro-4-hydroxy-6-methyl-2-oxo- 2H-pyrano-3
      carbothioamides with hydrazine is described. Some compounds showed remarkable
      antipyretic, analgesic, antiarrhythmic and hypotensive activity in rats or mice,
      as well as weak antiinflammatory, local anesthetic and in vitro platelet
      antiaggregating activity.

PMID- 8135994
TI  - Nasal formulations of ketorolac tromethamine: technological evaluation-
      bioavailability and tolerability in rabbits.
AB  - This paper describes the development of a novel formulation of the powerful non
      narcotic analgesic ketorolac tromethamine. This drug is given orally three to
      four times/day to deliver a total of 30 to 60 mg of drug. Higher doses cannot be
      given orally because of gastrointestinal side effects and intramuscular
      injections, three times/day must then be used. The need for injections limits the
      drug to a clinical setting. Nasal delivery offers a method of achieving the high
      blood levels of repeated intramuscular injections in a formulation that can be
      easily applied by the patients. Four formulations were evaluated in "in vitro"
      and "in vivo" rabbit tests. The best formulation consisted of a 5% solution of
      ketorolac tromethamine containing 0.3% sodium glycocolate as a known mucosal drug
      absorption enhancer. Ketorolac applied in this way had a bioavailability greater
      than 80%. The controlled release nature of nasal delivery also doubled the drug's
      apparent half life. The drug formulation was stable in three-months stability
      tests and produced minimal nasal irritation.

PMID- 8135995
TI  - Synthesis and antifungal activity of pyrido[3',2':4,5]thieno[3,2-d]- 1,2,3
      triazine derivatives.
AB  - The antimicrobial activity of some pyrido[3',2':4,5]thieno[3,2-d]- 1,2,3-triazine
      derivatives has been studied. Some compounds proved effective against
      microorganisms in vitro, compounds 3a and 3c in particular exhibited antifungal
      activity, comparable to MCZ, against hyphomycetes.

PMID- 8135996
TI  - Synthesis and antimicrobial activity of some 1,5-diaryl-2-methyl-3- carbethoxy-4
      (4-methyl-piperazin-1-ylmethyl)-pyrroles and some 1,5-diaryl-2- methyl-3,4-di(4
      methyl-piperazin-1-ylmethyl)-pyrroles.

PMID- 8135997
TI  - A vision of the challenges: changes in Medicare.

PMID- 8135998
TI  - The Clinton healthcare plan.

PMID- 8135999
TI  - The impact of the new DMERC medical policy on surgical dressings.

PMID- 8136000
TI  - Accepting ownership in the management of pressure ulcers.

PMID- 8136001
TI  - Algorithm for burn injury topical management.

PMID- 8136002
TI  - Survival skills: a patient teaching model for wound care.

PMID- 8136003
TI  - HCFA announces grandfathering provisions for Medicare part B surgical dressing
      policies.

PMID- 8136004
TI  - Recommendations made for DMERC regional drafts of support surface policy.

PMID- 8136005
TI  - Multi-center evaluation of a new wound dressing.
AB  - Ninety-two wounds were evaluated for at least three dressing changes each. The
      vast majority of the wounds were lightly exuding Stage II pressure ulcers and
      skin tears. This evaluation confirmed the hypothesis that the protective,
      conformable, and elastic properties of Flexzan, combined with its limited
      absorption capacity, high moisture vapor permeability and easy to use adhesive
      system, provided a dressing well suited to the management of the non- to lightly
      exuding wounds included. In addition, it was found to be a "superior" secondary
      dressing for alginate dressings on highly exuding wounds.

PMID- 8136006
TI  - T-cell based cancer immunotherapy: direct or redirected tumor-cell recognition?
AB  - In development of strategies for immunotherapy of cancer a new emphasis is
      emerging, termed T-cell retargeting, which involves artificial redirection of
      cytotoxic T lymphocytes (CTL) against cancer cells, using bispecific reagents. In
      this article, Gideon Beun, Cornelis van de Velde and Gert Jan Fleuren evaluate
      this potential strategy for cellular immunotherapy, and propose how the gap
      between in vitro results and clinical application might be bridged.

PMID- 8136007
TI  - Is restricted antigen presentation the explanation for fetal allograft survival?
AB  - Mammalian embryos express paternal histocompatibility antigens which make them
      potential targets for the maternal immune system. The trophoblast is a major
      histocompatibility complex (MHC) antigen-negative barrier between mother and
      fetus which facilitates movement of antigenic molecules but prevents traffic of
      antigenic cells and is itself unable to present antigen. Gary Wood suggests that
      the lack of antigen presentation requirements for MHC class I-restricted T-cell
      responses prevent generation of paternal-antigen directed cell-mediated immunity.

PMID- 8136008
TI  - Heavy-chain directed B-cell maturation: continuous clonal selection beginning at
      the pre-B cell stage.
AB  - A number of laboratories have demonstrated a biased representation of certain V
      region segments in the primary B-cell repertoire. This may reflect clonal
      selection at the pre-B cell stage of differentiation. Here, Robert Schwartz and
      David Stollar suggest that pre-B cells undergo positive selection directed by the
      presence of surface heavy chain with low affinity to autoantigen. This mechanism
      would account for the anti-self property of the pre-immune B-cell repertoire.

PMID- 8136009
TI  - Indirect presentation of MHC antigens in transplantation.
AB  - T cells can recognise foreign major histocompatibility complex (MHC) antigens by
      two distinct routes, either directly as intact molecules or indirectly as
      peptides after antigen processing. Danny Shoskes and Kathryn Wood review the
      evidence that indirect presentation of allopeptides may play a significant role
      in the events leading to the rejection or acceptance of allo- and xenografts.

PMID- 8136010
TI  - Pituitary control of immune cells.

PMID- 8136011
TI  - HLA mimicry by HIV-1 gp120 in the pathogenesis of AIDS.

PMID- 8136012
TI  - Factors affecting TCR-repertoire diversity.

PMID- 8136013
TI  - Characterization of specific T cells in myasthenia gravis.

PMID- 8136014
TI  - Oxidative stress as a mediator of apoptosis.
AB  - Many agents which induce apoptosis are either oxidants or stimulators of cellular
      oxidative metabolism. Conversely, many inhibitors of apoptosis have antioxidant
      activities or enhance cellular antioxidant defenses. Mammalian cells exist in a
      state of oxidative siege in which survival requires an appropriate balance of
      oxidants and antioxidants. Thomas Buttke and Paul Sandstrom suggest that
      eukaryotic cells may benefit from this perilous existence by invoking oxidative
      stress as a common mediator of apoptosis.

PMID- 8136015
TI  - Thermal inactivation of butyrylcholinesterase and acetylcholinesterase.
AB  - Differences were observed in the extent of thermal inactivation of human
      butyrylcholinesterase (BuChE) and eel acetylcholinesterase (AChE). BuChE was more
      resistant to 57 degrees C inactivation than was AChE. Thermal inactivation of
      BuChE was reversible and followed first-order kinetics. AChE thermal inactivation
      was irreversible and did not follow first-order kinetics. AChE was marginally
      protected from thermal inactivation by the "nonspecific salts" ammonium sulfate
      and sodium chloride and to a greater extent by the "active site-specific salts"
      choline chloride, sodium acetate, and acetylcholine iodide. This protection was
      accompanied by a loss of absorbance at 280 nm. This data supports the hypothesis
      that thermal inactivation of AChE occurs by conformational scrambling and that
      aromatic amino acid residue(s) are involved in this process.

PMID- 8136016
TI  - Autoreactive sites of human lambda light chain mapped by comprehensive peptide
      synthesis.
AB  - Autoantibodies reactive against immunoglobulins are associated with autoimmune
      disorders as well as with immunization and infection. Moreover, recent interest
      is focused on auto-antidiotypes because of their possible role in
      immunoregulation. In this study, we used a set of overlapping synthetic peptides
      duplicating the structure of the monoclonal human lambda light chain Mcg to map
      autoreactive determinants recognized by natural antibodies present in normal
      polyclonal human IgG. We found that autoantibodies in human IgG react strongly
      with two distinct V lambda determinants corresponding to the first
      complementarity determining region (CDR1) and the third framework (Fr3).
      Antibodies showing weak reactivities against three regions of the constant domain
      also occur in the preparations. The antibodies directed against light chain
      peptides comprise less than 0.1% of the IgG pool. Analysis by direct binding and
      by competitive ELISA inhibition established that affinity purified antibodies
      specific for CDR1 and Fr3 peptide determinants react with the intact light chain
      Mcg as well as with the corresponding peptide. Competitive inhibition studies
      comparing total IgG and affinity-purified antibodies indicate that natural
      antibodies showing a wide range of affinities are present. The polyclonal nature
      of the natural antibodies is further shown by the presence of both kappa and
      lambda light chains in the purified antibodies. Although the role of such natural
      antibodies remains to be determined, the cross-reactivity between V lambda
      peptides and the intact chain suggest that they can function in regulation of
      antibody formation.

PMID- 8136017
TI  - Immunological and biochemical study on tissue and subcellular distributions of
      protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase):
      a simplified and efficient procedure for high quantity purification from brain.
AB  - Although protein kinase FA/GSK-3 alpha (an activating factor of ATP.Mg-dependent
      protein phosphatase) has been established as a cytosolic enzyme in mammalian
      nonnervous tissues involved in the metabolic regulation, immunological and
      biochemical studies on tissue and subcellular distributions demonstrate that
      kinase FA/GSK-3 alpha is in fact a membrane-associated enzyme and most abundantly
      exists in brain particulate membrane fractions depending on the tissue
      homogenization conditions. For instance, when brain was homogenized in Polytron
      without 0.32 M sucrose, approximately 40% of the total FA/GSK-3 alpha was found
      in the cytosol. However, when brain was homogenized in buffer containing 0.32 M
      sucrose and in a glass homogenizer with Teflon pestle, more than 80% of the total
      FA/GSK-3 alpha was found associated with the particulate membrane fractions. By
      manipulating these findings, we have developed a simplified procedure for
      purification of homogeneous kinase FA/GSK-3 alpha in high recovery and in a
      substantial amount from brain tissue. The data explain why kinase FA/GSK-3 alpha
      cannot be isolated in a reasonable amount from most mammalian tissues for the
      past years. The specific pure antibody that can specifically recognize kinase
      FA/GSK-3 alpha from crude tissue extracts together with the high quantity
      purification of the enzyme as presented in this report provides an initial key
      step for studies on the role of kinase FA/GSK-3 alpha in the regulation of brain
      functions especially in the brain particulate membrane fractions.

PMID- 8136019
TI  - Densimetric determination of equilibrium binding of sucrose octasulfate with
      basic fibroblast growth factor.
AB  - Fibroblast growth factors (FGFs) strongly bind to heparin and are thereby
      stabilized against deactivation and proteolytic cleavage. Sucrose octasulfate
      (SOS), which has a chemical structure resembling the repeating unit of heparin,
      has also been shown to enhance stability of basic FGF against thermal
      denaturation and to induce a small conformational change. We have examined SOS
      binding to bFGF using equilibrium dialysis. The difference in SOS concentration
      across the dialysis membrane was measured using a precision density meter, since
      the density of SOS differs greatly from that of water. With care, this
      densimetric technique can measure binding with a precision of +/- 0.1 mol/mol
      using about 2 mg/ml of protein. These results show that the binding saturates at
      2 mol of SOS per mole of bFGF as the SOS concentration increases to 3.6 mM or
      higher. The effect of SOS on the thermal stability of bFGF was examined using
      denaturation at a constant heating rate, by both turbidity and differential
      scanning calorimetry. Since the thermal denaturation is irreversible, the
      temperature where aggregation abruptly increases was taken to indicate the onset
      of denaturation. This temperature increased by approximately 12 degrees C as the
      SOS concentration increased from 0.018 to 3.6 mM and remained constant above 3.6
      mM, consistent with our binding data if the binding is specific to the native
      state.

PMID- 8136018
TI  - Interaction of thrombin with antithrombin, heparin cofactor II, and protein C
      inhibitor.
AB  - alpha-Thrombin is a trypsin-like serine proteinase involved in blood coagulation
      and wound repair processes. Thrombin interacts with many macromolecular
      substrates, cofactors, cell-surface receptors, and blood plasma inhibitors. The
      three-dimensional structure of human alpha-thrombin shows multiple surface
      "exosites" for interactions with these macromolecules. We used these coordinates
      to probe the interaction of thrombin's active site and two exosites, anion
      binding exosite-I and -II, with the blood plasma serine proteinase inhibitors
      (serpins) antithrombin (AT), heparin cofactor II (HC), and protein C inhibitor
      (PCI). Heparin, a widely used anticoagulant drug, accelerates the rate of
      thrombin inhibition by AT, PCI, and HC. Thrombin Quick II is a dysfunctional
      thrombin mutant with a Gly 226-->Val substitution in the substrate specificity
      pocket. We found that thrombin Quick II was inhibited by HC, but not by AT or
      PCI. Molecular modeling studies suggest that the larger Val side chain protrudes
      into the specificity pocket, allowing room for the smaller P1 side chain of HC
      (Leu) but not the larger P1 side chain of AT and PCI (both with Arg). gamma T
      Thrombin and thrombin Quick I (Arg 67-->Cys) are both altered in anion-binding
      exosite-I, yet bind to heparin-Sepharose and can be inhibited by AT, HC, and PCI
      in an essentially normal manner in the absence of heparin. In the presence of
      heparin, inhibition of these altered thrombins by HC is greatly reduced compared
      to both AT and PCI. alpha-Thrombin with chemically modified lysines in both anion
      binding exosite-I and -II has no heparin accelerated thrombin inhibition by
      either AT or HC. Thrombin lysine-modified in the presence of heparin has
      protected residues in anion-binding exosite-II and the loss of heparin
      accelerated inhibition by HC is greater than that by AT. Collectively, these
      results suggest differences in serpin reactive site recognition by thrombin and a
      more complicated mechanism for heparin-accelerated inhibition by HC compared to
      either AT or PCI.

PMID- 8136020
TI  - Carbon-13 NMR studies of the lysine side chains of calmodulin and its proteolytic
      fragments.
AB  - The pH-titration and dynamic behaviour of the seven lysine side chains in bovine
      calmodulin were studied by carbon-13 NMR. The amino groups of the calcium
      saturated protein and its proteolytic fragments TR1C (1-75) and TR2C (78-148)
      were dimethylated with carbon-13 labeled formaldehyde; this modification did not
      alter the protein's structure or its ability to activate the enzyme cyclic
      nucleotide phosphodiesterase. Tentative assignments for 5 out of the 7 dimethyl
      lysine resonances could be obtained by comparing spectra of the fully and
      partially modified protein, with those of the proteolytic fragments. The pKa
      values measured for calcium saturated calmodulin ranged between 9.5 (Lys 75) and
      10.2 (Lys 13); two residues (Lys 94 and Lys 13) showed a biphasic titration curve
      suggesting their possible involvement in ion-pairs. The dynamic behavior of the
      lysine side chains was deduced from spin lattice relaxation measurements. All
      side chains were flexible and this was not influenced by the removal of calcium,
      or the addition of the calmodulin antagonist trifluoperazine. The latter data
      suggest that the lysine side chains are not directly involved in calmodulin's
      target binding sites.

PMID- 8136021
TI  - Studies on the specificity of HIV protease: an application of Markov chain
      theory.
AB  - A sequence-coupled (Markov chain) model is proposed to predict the cleavage sites
      in proteins by proteases with extended specificity subsites. In addition to the
      probability of an amino acid occurring at each of these subsites as observed from
      a training set of oligopeptides known cleavable by HIV protease, the conditional
      probabilities as reflected by the neighbor-coupled effect along the subsite
      sequence are also taken into account. These conditional probabilities are derived
      from an expanded training set consisting of sufficiently large peptide sequences
      generated by the Monte Carlo sampling process. Very high accuracy was obtained in
      predicting protein cleavage sites by both HIV-1 and HIV-2 proteases. The new
      method provides a rapid and accurate means for analyzing the specificity of HIV
      protease, and hence can be used to help find effective inhibitors of HIV protease
      as potential drugs against AIDS. The principle of this method can also be used to
      study the specificity of any multisubsite enzyme.

PMID- 8136022
TI  - The complete primary structure of ribosomal protein L1 from Thermus thermophilus.
AB  - The primary structure of the 23S rRNA binding ribosomal protein L1 from the 50S
      ribosomal subunit of Thermus thermophilus ribosomes has been elucidated by direct
      protein sequencing of selected peptides prepared by enzymatic and chemical
      cleavage of the intact purified protein. The polypeptide chain contains 228 amino
      acids and has a calculated molecular mass of 24,694 D. A comparison with the
      primary structures of the corresponding proteins from Escherichia coli and
      Bacillus stearothermophilus reveals a sequence homology of 49% and 58%,
      respectively. With respect to both proteins, L1 from T. thermophilus contains
      particularly less Ala, Lys, Gln, and Val, whereas its content of Glu, Gly, His,
      Ile, and Arg is higher. In addition, two fragments obtained by limited
      proteolysis of the intact, unmodified protein were characterized.

PMID- 8136023
TI  - Assignment of the three disulfide bridges of huwentoxin-I, a neurotoxin from the
      spider selenocosmia huwena.
AB  - The positions of the disulfide bonds of huwentoxin-I, a neurotoxin from the
      spider Selenocosmia huwena, have been determined. The existence of three
      disulfide bonds in the native toxin was demonstrated by mass spectroscopy and the
      lack of reactivity with a thiol reagent. The assignment procedure involved a
      combination of tryptic digestion of the native toxin and sequence analysis of
      both intact and in situ S-carboxymethylated toxin. In situ carboxymethylation is
      shown to be a useful procedure in sequencing of cysteine- and cystine-containing
      peptides. Sequence analysis of the intact, cross-linked toxin indicated that no
      amino acid phenylthiohydantoin (PTH) derivative is seen for the first half
      cystine in a cross-linked pair, but that the PTH of dehydroalanine, which can be
      detected at 313 nm, is seen at the position of the second half-cystine. By
      sequencing disulfide cross-linked tryptic fragments, the three disulfide linkages
      in huwentoxin-I could be assigned as Cys2-Cys17, Cys9-Cys22, and Cys16-Cys29.

PMID- 8136024
TI  - Contribution of the B16 and B26 tyrosine residues to the biological activity of
      insulin.
AB  - We report the synthesis and biological evaluation of five insulin analogues in
      which one or both of the B-chain tyrosine residues have been substituted. [B16
      Phe]insulin and [B16 Trp]insulin display a very modest reduction in potency (c.
      65%) relative to porcine insulin; [B26 Phe]insulin is less active (30-50%), and
      the doubly substituted [B16 Phe, B26 Phe]insulin displays still lower potency (c.
      35%). The further substitution of Asp for B10 His in [B16 Phe, B26 Phe]insulin
      raises its activity to approximately twofold greater than natural insulin, an
      increase of approximately fivefold over the parent compound. We conclude that the
      bulk and/or aromaticity of the amino acid residue at position B16, but not its
      hydrogen-bonding capacity, contributes to the biological activity of the hormone.
      We further conclude that hydrogen-bonding capacity or special side-chain packing
      characteristics are required at the B26 position for insulin to display high
      biological activity.

PMID- 8136025
TI  - Lipases from Rhizomucor miehei and Humicola lanuginosa: modification of the lid
      covering the active site alters enantioselectivity.
AB  - The homologous lipases from Rhizomucor miehei and Humicola lanuginosa showed
      approximately the same enantioselectivity when 2-methyldecanoic acid esters were
      used as substrates. Both lipases preferentially hydrolyzed the S-enantiomer of 1
      heptyl 2-methyldecanoate (R. miehei: ES = 8.5; H. lanuginosa: ES = 10.5), but the
      R-enantiomer of phenyl 2-methyldecanoate (ER = 2.9). Chemical arginine specific
      modification of the R. miehei lipase with 1,2-cyclohexanedione resulted in a
      decreased enantioselectivity (ER = 2.0), only when the phenyl ester was used as a
      substrate. In contrast, treatment with phenylglyoxal showed a decreased
      enantioselectivity (ES = 2.5) only when the heptyl ester was used as a substrate.
      The presence of guanidine, an arginine side chain analog, decreased the
      enantioselectivity with the heptyl ester (ES = 1.9) and increased the
      enantioselectivity with the aromatic ester (ER = 4.4) as substrates. The
      mutation, Glu 87 Ala, in the lid of the H. lanuginosa lipase, which might
      decrease the electrostatic stabilization of the open-lid conformation of the
      lipase, resulted in 47% activity compared to the native lipase, in a tributyrin
      assay. The Glu 87 Ala mutant showed an increased enantioselectivity with the
      heptyl ester (ES = 17.4) and a decreased enantioselectivity with the phenyl ester
      (ER = 2.5) as substrates, compared to native lipase. The enantioselectivities of
      both lipases in the esterification of 2-methyldecanoic acid with 1-heptanol were
      unaffected by the lid modifications.

PMID- 8136026
TI  - Assignment of all four disulfide bridges in echistatin.
AB  - Echistatin is a 49-amino-acid protein from Echis carinatus venom. It contains
      four disulfide bonds. Since the disulfide bonding is critical for biological
      activity; it is very important to assign the disulfide linkage in this protein.
      Echistatin was incubated in 250 mM oxalic acid at 100 degrees C for 4 hr under
      nitrogen. Under these conditions, many overlapping disulfide-containing peptides
      were identified by ionspray mass spectrometry. Ionspray MS/MS data indicate that
      the four disulfide bonds are Cys 2-Cys 11, Cys 7-Cys 32, Cys 8-Cys 37, and Cys 20
      Cys 39. To our knowledge, this is the first time all four disulfide bonds in
      echistatin have been assigned in one experiment without disulfide bond exchange.
      This approach, which combines oxalic acid hydrolysis and ionspray MS/MS, may be
      very useful for assigning disulfide bridges in other proteins from the
      disintegrin family.

PMID- 8136027
TI  - Purification and partial sequence of proteins involved in the cholic acid
      transport into rat liver hepatocytes.
AB  - Two proteins, in previous work labeled by affinity markers derived from
      taurocholic acid, were purified and partially sequenced. Antibodies were raised
      against purified proteins, and cross-reactions were carefully checked. The
      influence of these antibodies upon taurocholic acid import into vesicles from rat
      liver plasma membranes was measured, and showed a distinct inhibition of
      transport in the case of the 54 kD protein.

PMID- 8136028
TI  - Chemical characterization and location of ionic interactions involved in the
      assembly of the C1 complex of human complement.
AB  - The C1 complex of human complement comprises two loosely interacting subunits,
      C1q and the Ca(2+)-dependent C1s-C1r-C1r-C1s tetramer. With a view to gain
      information on the nature of the ionic interactions involved in C1 assembly, we
      have studied the effects of the chemical modifications of charged residues of C1q
      or the tetramer on their ability to reconstitute the C1 complex. Treatment of C1q
      with pyridoxal-5'-phosphate, acetic anhydride, and citraconic anhydride, as well
      as with cyclohexanedione and diethylpyrocarbonate, inhibited its ability to
      associate with C1s-C1r-C1r-C1s. Treatment of the collagen-like fragments of C1q
      with the same reagents yielded the same effects. Treatment of C1s-C1r-C1r-C1s
      with 1-ethyl-3-[-3-(dimethylamino) propyl] carbodiimide also prevented C1
      assembly, through modification of acidic amino acids which were shown to be
      located in C1r. Further studies on the location of the interaction sites within
      C1q, using ligand-blotting and competition experiments with synthetic peptides,
      were unsuccessful, suggesting that these sites are contributed to by two or three
      of the C1q chains. It is concluded that C1 assembly involves interactions between
      acidic amino acids of C1r and lysine (hydroxylysine) and arginine residues
      located within the collagen-like region of C1q. Sequence comparison with mannan
      binding protein, another collagen-like molecule which binds the C1s-C1r-C1r-C1s
      tetramer, suggests Arg A38, and HyL B32, B65, and C29 of C1q as possible
      interaction sites.

PMID- 8136029
TI  - Critical amino acids responsible for converting specificities of proteins and for
      enhancing enzyme evolution are located around beta-turn potentials: data-based
      prediction.
AB  - Various reports have described that amino acid substitutions can alter substrate,
      positional, inhibitory, and target gene specificities of proteins. By using the
      method of Chou and Fasman, the present work predicts that critical amino acids
      for converting these substrate specificities of trypsin, L-lactate dehydrogenase,
      aspartate aminotransferase, beta-lactamase, and cytochrome P-450 are found to
      exist within regions predicted as beta-turns. The ratios of hydroxylation and
      oxygenation positions of substrates by cytochrome P-450 and lipoxygenase,
      respectively, are varied by changes of the protein structures, probably around
      turn conformations. Inhibitory specificities of bovine pancreatic trypsin
      inhibitor and alpha 1-antitrypsin and target gene specificity of glucocorticoid
      receptor are converted by changing turn structures. Occurrence of beta-turn
      probabilities can be predicted around the amino acid alteration positions of an
      evolutionally antecedent protein of a nylon degradation enzyme. These findings
      will have relevance to work on protein engineering and enzyme evolution.

PMID- 8136030
TI  - Starch- and glycogen-debranching and branching enzymes: prediction of structural
      features of the catalytic (beta/alpha)8-barrel domain and evolutionary
      relationship to other amylolytic enzymes.
AB  - Sequence alignment and structure prediction are used to locate catalytic alpha
      amylase-type (beta/alpha)8-barrel domains and the positions of their beta-strands
      and alpha-helices in isoamylase, pullulanase, neopullulanase, alpha-amylase
      pullulanase, dextran glucosidase, branching enzyme, and glycogen branching
      enzymes--all enzymes involved in hydrolysis or synthesis of alpha-1,6-glucosidic
      linkages in starch and related polysaccharides. This has allowed identification
      of the transferase active site of the glycogen debranching enzyme and the
      locations of beta-->alpha loops making up the active sites of all enzymes
      studied. Activity and specificity of the enzymes are discussed in terms of
      conserved amino acid residues and loop variations. An evolutionary distance tree
      of 47 amylolytic and related enzymes is built on 37 residues representing the
      four best conserved beta-strands of the barrel. It exhibits clusters of enzymes
      close in specificity, with the branching and glycogen debranching enzymes being
      the most distantly related.

PMID- 8136031
TI  - Identification of nodulation genes (nod locus 5) from Azorhizobium caulinodans
      ORS571.
AB  - An 800 bp AccI-PUCII DNA containing promoter region of nodABC (P1) from A.
      caulinodans ORS571 was cloned and used as a hybridization probe against the
      chromosome DNA, which led to the identification of another 8.4-kb EcoRI fragment
      showing homology to P1. A corresponding clone of 8.4-kb DNA was isolated from a
      pLAFI gene bank (pRG90). The restriction enzyme analysis and DNA-DNA
      hybridization of 8.4-kb DNA indicated the P1 homology was located in the 450-bp
      SmaI-SphI region (P2 region). omega insertion deletion of 8.4 kb DNA resulted in
      a mutant strain ORS571-5 that delayed to nodulate the stems of S. rostrata. This
      phenotype was complemented by the introduction of pRK84 carrying nod locus 5 DNA.

PMID- 8136032
TI  - The functional linkage among the "ZSL"-spinal dorsal horn-SN.
AB  - Electrical stimulation of the Zusanli point (ZSL) and solitary tract nucleus (SN)
      as well as microelectrode recording from the laminae III-V of the lumbar spinal
      dorsal horn have been used on the pentobarbital anesthetized rats, finding and
      identifying 57 spinal neurons responding to the stimulations of both ZSL and SN.
      Among them, 34 responded antidromically to SN; the others responded
      orthodromically to SN. Among them, the low-threshold mechano-receptive (LTM)
      neurons and wide-dynamic-range (WDR) neurons were 50 percent respectively. The
      results indicate that (i) a single spinal dorsal horn neuron receives somatic
      afferent input and then conveys it to the visceral sensory nucleus-SN; (ii) some
      spinal dorsal horn neurons receive, in turn, innervation from the SN; (iii) the
      convergence and integration between somatic and visceral sensory inputs might
      occur in the spinal dorsal horn neurons and/or SN.

PMID- 8136033
TI  - Purification and properties of acetylcholinesterase from human brain.
AB  - Acetylcholinesterase from human caudate nucleus and partial thalamus was purified
      by using Con A-Sepharose, short-arm and long-arm ligand Sepharose affinity
      chromatographies. SDS-PAGE of the purified AChE under the reduced condition
      showed one main band, corresponding to a molecular weight of 66 kD. The purified
      AChE with a specific activity of 3384 U/mg protein represented 20% activity of
      the homogenate supernatant. Analysis of purified AChE by gradient slab PAGE and
      DISC-PAGE with activity staining revealed the existence of monomer, dimer,
      tetramer, hexamer and octomer of the enzyme. The isoelectric point of AChE ranged
      between pH 5.6 and 6.0. Con A-Sepharose affinity chromatography retained most of
      the applied AChE activity implying that the enzyme is a kind of glycoprotein. The
      isolated human brain AChE had no cross-immunoreactivity with 3F3 and weak cross
      immunoreactivity with 2G8 and 1H11 anti-Torpedo AChE antibodies. Balb/c mice were
      immunized with human cerebellum AChE purified with Con A and short-arm ligand
      affinity chromatographies. The antiserum produced showed strong cross
      immunoreactivity with Torpedo AChE but weak cross-immunoreactivity with human RBC
      membrane AChE. The purified human brain striatum AChE was reduced and alkylated,
      and then hydrolyzed by immobilized TPCK-treated trypsin. Trypsin peptides in the
      hydrolysate was separated by RP-HPLC. Several large peptide peaks and numbers of
      small peaks were observed. The large peaks showed obvious immunoreactivity with
      the mouse anti human cerebellum AChE antiserum.

PMID- 8136034
TI  - Preliminary fluorimetric screening of fourteen palladium complexes as potential
      antitumor agents.
AB  - Making use of the fact that the combination of a drug substance with DNA may
      inhibit the duplication, synthesis and proliferation of DNA and the consistency
      of the in vivo and in vitro interactions, the authors worked out a preliminary
      screening method for testing complex agents as potential antitumor drugs using
      ethidium bromide as a fluorescence probe. In this report, the method was applied
      for in vitro testing fourteen synthesized palladium(II)/phenanthroline/amino
      acid/chloride complexes as potential non-platinum antitumor agents. The
      fluorimetric screening method was compared with methylene blue tube test and
      trypan blue dye exclusion assay. All three methods gave agreeable results. Among
      the complexes tested, [Pd(phen)(lys)]Cl, [Pd(phen)(arg)]Cl and [Pd(phen)(pro)]Cl
      showed antineoplastic ratios for animal tumor S-180 56%, 50% and 48%,
      respectively, in accordance with the order of their binding constants with DNA,
      7.96 x 10(6), 4.52 x 10(6) and 1.0 x 10(6), respectively. The test results show
      that fluorimetric method is simple, cheap and rapid, suitable for preliminary
      screening of antitumor complexes.

PMID- 8136035
TI  - Synthesis and expression in Escherichia coli of a human neutrophil activating
      protein-1/interleukin-8 gene.
AB  - The complete gene coding for human neutrophil activating protein-1/interleukin-8
      was synthesized using a semi-chemical semi-enzymatic method. The synthetic gene
      was then overexpressed in Escherichia coli under the temperature-regulated
      control of the PRPL tandem promoters. As determined by SDS-PAGE and densitometry,
      the overexpressed protein comprised up to 18.5% and 10.9% of the total soluble
      protein in E. coli cells grown in shake flasks and in batch fermentation,
      respectively. The recombinant NAP-1/IL-8 was then purified to > 95% homogeneity
      by gel filtration and cation exchange chromatography. The purified protein
      appeared as a single band on the SDS-PAGE gel and possessed potent chemotactic
      activity in the concentration of < 10 ng/ml, as assayed by the agarose plate
      method. An early skin reactivity was also observed when the pure NAP-1/IL-8 was
      injected subcutaneously into the rabbits. The N-terminal 36 amino acid sequence
      of the recombinant NAP-1/IL-8 was determined using the Edman method and was shown
      to be identical to that of the native protein.

PMID- 8136036
TI  - Relatively between extrication wave of mental load (EML) and emotion.
AB  - This experiment which was divided into three items studied the relativity between
      normal human emotion and extrication wave of mental load (EML) in a paradigm of
      combining CNV feedback with EML. Fourteen young persons were taken as subjects.
      After Fz, Cz, Pz, P3-T5 and P4-T6 were recorded, shorter EML latency and higher
      EML amplitude were caused by positive emotion in comparison with those caused by
      negative emotion. EML changes of the five recorded points were consistent under
      the effects of positive and negative emotions. This experiment also discussed the
      question of EML brain sources. Under the emotional conditions provided in the
      present experiment, EML possibly can be regarded as ERP index reflecting its
      positive and negative attributes.

PMID- 8136037
TI  - Naturally occurring benzodiazepines and benzodiazepine-like molecules in brain.
AB  - Great progress has been made in the last five years in demonstrating the presence
      of benzodiazepines (BZDs) in mammalian tissues, in beginning studies on the
      origin of these natural compounds and in elucidating their possible biological
      roles. Many unanswered questions remain regarding the sources and the
      biosynthetic pathways responsible for the presence of BZDs in brain and their
      different physiological and/or biochemical actions. This essay will focus on
      recent findings supporting that: (1) BZDs are of natural origin; (2) mammalian
      brain contains BZDs in concentrations ranging between 5.10(-10) to 10(-8) M; (3)
      BZDs and BZD-like molecules are unevenly distributed in brain; the highest
      concentration is found in limbic structures (4) dietary source of BZDs might be a
      plausible explanation for their occurrence in animal tissues, including man; (5)
      the formation of BZDs-like molecules in brain is a possibility, experimentally
      supported; (6) BZDs like molecules including diazepam and N desmethyldiazepam are
      elevated in hepatic encephalopathy; (7) natural BZDs in the brain are involved in
      the modulation of memory processes. Future studies using the full range of
      biochemical, physiological, behavioral and molecular biological techniques
      available to the neuroscientist will hopefully continue to yield new and exciting
      information concerning the biological roles that BZDs might play in the normal
      and pathological functioning of the brain.

PMID- 8136038
TI  - Foetal grafts from hippocampal regio superior alleviate ischaemic-induced
      behavioural deficits.
AB  - Transitory global cerebral ischaemia produced in rats by four vessel occlusion
      for 15 min produced substantial loss of CA1 cells in dorsal hippocampus and
      minimal other intra- and extra-hippocampal damage. Ischaemic rats showed a long
      lasting impairment in spatial navigation in the water maze, and such impairment
      was sensitive to task difficulty. Groups of ischaemic animals were implanted with
      foetal tissue dissected from hippocampal regio superior (SUP--containing CA1
      field), regio inferior (INF--containing dentate gyrus), and basal forebrain, with
      grafts sited in the alveus above the damaged CA1 region. Behavioral testing in
      the water maze (acquisition, retention and a working memory task) was conducted
      over a period of 4 to 12 weeks after grafting. Only rats receiving the SUP graft
      showed consistent improvement in water maze performance, relative to ischaemic
      controls, when tested in retention and working memory. Although the selective
      effect of CA1-containing grafts suggests repairing of the damaged host circuit,
      functional recovery may have been related to the greater ability of SUP grafts to
      survive and grow in the host ischaemic hippocampus.

PMID- 8136039
TI  - Subordination stress: behavioral, brain, and neuroendocrine correlates.
AB  - In mixed-sex rat groups consistent asymmetries in offensive and defensive
      behaviors of male dyads are associated with the development of dominance
      hierarchies. Subordinate males can be differentiated from dominants on the basis
      of both agonistic and non-agonistic behaviors, wound patterns, weight changes.
      Their behavior changes suggest chronic defensiveness and are also broadly
      isomorphic to many of the symptoms of depression; their voluntary alcohol
      consumption increases, and their life-spans are shortened. Both subordinate and
      dominant males tend to show organ change compared to non-grouped controls, with
      adrenal and spleen enlargement and thymus reduction. However, these changes
      appear to be more marked in subordinates, and only subordinates show reduced
      testes weights. Basal corticosterone (CORT) levels were sharply higher, and
      plasma testosterone (T) sharply lower, in subordinates compared to both dominants
      and controls, and reduced corticosterone binding globulin further enhanced free
      CORT for subordinates particularly. Many subordinates failed to show a normal
      CORT response to restraint stress. Subordinates also appear to show widespread
      changes in serotonin systems, with increased 5-HIAA/5-HT ratios in a number of
      brain areas, and alterations of 5-HT1A receptor binding at some sites. These
      changes suggest that subordination, a common and consistent feature of life for
      many animals living in social groups, may be a particularly relevant model for
      investigating the behavioral, neural and endocrine correlates of chronic stress.

PMID- 8136040
TI  - Role of the amygdala and periaqueductal gray in anxiety and panic.
AB  - The amygdala (AM) and the periaqueductal gray (PAG) represent the rostral and the
      caudal pole, respectively, of a longitudinally organized neural system, that is
      responsible for the integration of behavioral and physiological manifestations of
      defensive reactions against innate and learned threats. Microinjection of
      benzodiazepine (BZD) anxiolytics, GABAA receptor agonists or 5-HT receptor
      antagonists into the AM has anxiolytic effects in conflict tests and other models
      of conditioned fear, while similar administration of 5-HT or of a 5-HT1A receptor
      agonist has anxiogenic effects. On the other hand, in the test of electrical
      stimulation of the PAG, microinjection of 5-HT, 5-HT mimetics, or of drugs that
      enhance the action of endogenous 5-HT into the same brain area has an
      antiaversive effect, like BZD and GABAA agonists. Furthermore, microinjection of
      midazolam, of the NMDA receptor antagonist AP-7, or of the 5-HT1A/1B receptor
      blocker propranolol increased the exploration of the open arms of the elevated
      plus-maze, having therefore an anxiolytic effect. These results point to an
      inhibitory role of the GABA-BZD system in both the AM and the PAG. In contrast, 5
      HT seemingly enhances conditioned fear in the AM, while inhibiting unconditioned
      fear in the PAG. Thus, 5-HT2/1C antagonists reportedly release punished behavior
      when injected into the AM, whereas they antagonized the antiaversive effect of 5
      HT, zimelidine and 5-HT1A/1B receptor blockers in the PAG. Since reported
      clinical studies revealed that one of such compounds, ritanserin, relieves
      generalized anxiety but tends to aggravate panic disorder, a relationship may be
      established between the AM and anxiety and the PAG and panic.

PMID- 8136041
TI  - Hippocampal 5-HT receptors and consolidation of stressful memories.
AB  - It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus,
      innervated by 5-HT neurons localized in the median raphe nucleus, mediate
      adaptive or coping responses to aversive events and that dysfunction of this
      system is related to symptoms of depression. To test this hypothesis we
      investigated the expression of c-fos mRNA in animals submitted to immobilization
      stress. The results showed that c-fos mRNA expression is significantly increased
      in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of
      forced restraint, suggesting that this structure is activated during stress. To
      investigate the role of 5-HT neurotransmission in the hippocampus on adaptation
      to aversive events we immobilized rats for 2 h and tested them 24 h later in an
      elevated plus-maze. Our results showed that the previous restraint period
      decreases exploration of open arms in the maze. This effect was reversed by
      bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake
      blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonist, into the dorsal hippocampus
      immediately after restraint. These results are compatible with the idea that
      postsynaptic 5-HT1A receptors located in the hippocampus participate in the
      development of tolerance to aversive events.

PMID- 8136042
TI  - Thresholds of electrically induced defence reaction of the rat: short- and long
      term adaptation mechanisms.
AB  - The thresholds of electrically induced defence reaction of the rat were studied
      through the logistic fitting of the response output. When stepwise increasing
      stimuli were applied at the dorsal midbrain, hierarchically organized mean
      thresholds, spaced 10 microA apart, were observed for immobility, running and
      jumping defensive behaviours. The parallel threshold functions of these
      responses, ranked in the above order, denote that they have distinct output
      probabilities when induced with sequential stepwise increasing stimuli. In
      contrast, when single daily stimuli were given in a random order, virtually
      superimposed threshold functions were obtained for these defensive behaviours. In
      this case, since the same output probabilities would be expected for immobility,
      running and jumping behaviours, the defence system seems to operate in a state of
      maximum entropy. The above data suggest that the dorsal midbrain, including the
      deep collicular layers and the periaqueductal gray, may encode hierarchical or
      non-hierarchical defensive patterns which, respectively, mimic either the
      attentive behaviour of the prey watching the approaching predator or its chaotic
      behaviour when cornered by a sudden attack. On the other hand, whereas quite
      stable thresholds were observed for the somatic defensive responses when 5
      stimulation sessions were repeated over 15 days, the defecation and micturition
      output underwent a marked and progressive lessening. Since these autonomic
      responses have long been considered as reliable indexes of fear, their
      attenuation throughout the repeated sessions could express the rat adaptation to
      fear by the recurrence of the aversive experience. Taken together, these data
      suggest that while short-term neuronal adaptation could be responsible for the
      hierarchical threshold structure of the short interval stepwise stimulation, long
      term neuronal adaptation could underlie the selective decrease of defecation and
      micturition responses over repeated sessions of intracranial stimulation.

PMID- 8136043
TI  - Noradrenergic and cholinergic interactions in the amygdala and the modulation of
      memory storage.
AB  - Numerous studies have reported that, in rats, memory can be affected by
      manipulations of the amygdala noradrenergic system. Typically, low doses of
      norepinephrine facilitate while higher doses impair memory storage. Muscarinic
      cholinergic agonists facilitate, while antagonists impair memory storage. Recent
      evidence from studies using systemic injection of drugs, indicates that these two
      systems interact in modulating memory storage. The experiments reported here
      examined interactions between the amygdala noradrenergic and muscarinic
      cholinergic systems. The results indicate that activation of muscarinic
      cholinergic mechanisms in the amygdala enhances retention, and that such
      activation mediates the facilitatory effects of systemically administered
      oxotremorine. beta-Noradrenergic agonists appear to exert their effects in the
      amygdala by activating the release of acetylcholine.

PMID- 8136044
TI  - Fear-potentiated startle: a neural and pharmacological analysis.
AB  - The fear-potentiated startle paradigm has proven to be a useful system with which
      to analyze neural systems involved in fear and anxiety. This test measures
      conditioned fear by an increase in the amplitude of a simple reflex (the acoustic
      startle reflex) in the presence of a cue previously paired with a shock. Fear
      potentiated startle is sensitive to a variety of drugs such as diazepam,
      morphine, and buspirone that reduce anxiety in people and can be measured
      reliably in humans when the eyeblink component of startle is elicited at a time
      when they are anticipating a shock. Electrical stimulation techniques suggest
      that a visual conditioned stimulus ultimately alters acoustic startle at a
      specific point along the acoustic startle pathway. The lateral, basolateral and
      central amygdaloid nuclei and the caudal branch of the ventral amygdalofugal
      pathway projecting to the brainstem are necessary for potentiated startle to
      occur. The central nucleus of the amygdala projects directly to one of the
      brainstem nuclei critical for startle and electrical stimulation of this nucleus
      increases startle amplitude. Chemical or electrolytic lesions of either the
      central nucleus or the lateral and basolateral nuclei of the amygdala block the
      expression of fear-potentiated startle. The perirhinal cortex, which projects
      directly to the lateral and basolateral amygdaloid nuclei, plays a critical role
      in the expression of fear-potentiated startle using either visual or auditory
      conditioned stimuli. These latter amygdaloid nuclei may actually be the site of
      plasticity for fear conditioning, because local infusion of the NMDA antagonist
      AP5 into these nuclei blocks the acquisition of fear-potentiated startle. On the
      other hand, the expression of fear-potentiated startle is blocked by local
      infusion of the non-NMDA ionotropic antagonist CNQX or the G-protein inactivating
      toxin, pertussis toxin, but not by AP5. Finally, we have begun to investigate
      brain systems that might be involved in the inhibition of fear. Local infusion of
      AP5 into the amygdala was found to block the acquisition of experimental
      extinction, a prototypical method for reducing fear. We have also established a
      reliable procedure for producing both external and conditioned inhibition of fear
      potentiated startle and hope to eventually understand the neural systems involved
      in these phenomena.

PMID- 8136045
TI  - The periaqueductal gray-rostral medulla connection in the defence reaction:
      efferent pathways and descending control mechanisms.
AB  - Neuronal systems controlling cardiovascular components of emotional responses
      must have the capacity to generate different patterns of response and must also
      be able to modify those patterns in response to changes in environmental
      circumstances. Using the cardiovascular "defence" response as a model, evidence
      is presented to show that sympathetic premotor neurons of the rostral
      ventrolateral medulla (RVLM) possess such properties. Neurones in the RVLM act as
      relays in the descending efferent pathway to the sympathetic outflows from the
      dorsal periaqueductal gray matter (dPAG) which integrates the characteristic
      "defensive" pattern of cardiovascular response that accompanies activation of the
      midbrain aversive system. Activity in this pathway can be modulated, at the level
      of the RVLM, by a descending pathway which originates in the ventrolateral PAG.
      It is suggested that both the dorsolateral and the ventrolateral control systems
      in the PAG become activated during periods of physical or emotional stress,
      particularly those which involve sustained motor activity. Activity in the dorsal
      system initiates cardiovascular components of aversive/defensive behaviour whilst
      the ventrolateral system plays an important role in initiating the recuperative
      phase of behaviour characterised by sympathoinhibition, muscular relaxation and
      immobility which follows a stressful encounter.

PMID- 8136046
TI  - The interplay of learning and anxiety in the elevated plus-maze.
AB  - In naive rats benzodiazepines have clear anxiolytic effects in the elevated plus
      maze, but in rats with previous plus-maze experience benzodiazepines are
      ineffective. This phenomenon does not depend on the drug state on trial 1 or on
      the inter-trial interval and generalises across mazes of different material; it
      is dependent on experience of the open arm. The phenomenon of "one-trial
      tolerance" to the anxiolytic effect of benzodiazepines is not seen in other
      animal tests; and there is no equivalent phenomenon of "one-trial withdrawal" or
      of tolerance to anxiogenic effects in the plus-maze. The phenomenon is not seen
      in unhandled rats, in rats given longer trials in the plus-maze, or in those
      given an amnesic treatment on trial 1. It is suggested that during the first 5
      min in the elevated plus-maze the rats are acquiring a fear of heights and it is
      this phobic anxiety state that is measured during the second 5-min trial. Thus
      the nature of the anxiety generated by the maze is different on trials 1 and 2.
      The results of a factor analysis study confirm this conclusion.

PMID- 8136047
TI  - Multiple serotonin mechanisms in animal models of anxiety: environmental,
      emotional and cognitive factors.
AB  - Responses to serotonergic drugs in animal models of 'anxiety' are reviewed with
      emphasis on the elevated X-maze. Evidence for the 'classic' hypothesis, that
      decreasing serotonergic function is anxiolytic and increasing it anxiogenic, is
      most consistent in models of behavioural inhibition where the stimulus inhibits
      an approach response (conflict models). However, paradoxical drug effects are
      also frequent, especially where the aversive stimulus evokes an active response.
      Both types of drug effect are equally frequent in the elevated X-maze. 'Anxiety'
      models may detect multiple sites and mechanisms of action of the same drug; this
      may indicate multiple anxiety-related neurological mechanisms in the brain.
      However, not all drug effects in 'anxiety' models are necessarily related to
      anxiety itself. It is possible that cognitive factors may affect stimulus
      evaluation, and response inhibition by an aversive stimulus may be a special case
      of a wider role for serotonin in behavioural control. Clinical implications of
      these observations are considered.

PMID- 8136048
TI  - The periaqueductal gray and defensive behavior: functional representation and
      neuronal organization.
AB  - Recent findings suggest that the periaqueductal gray (PAG) can be subdivided on
      the basis of its anatomical connections and functional representation of
      cardiovascular and behavioral functions. This new scheme of subdivision
      postulates the existence of 4 major longitudinal columns located dorsomedial,
      dorsolateral, lateral and ventrolateral to the aqueduct. Attention has focussed
      on the lateral and ventrolateral columns, because they contain topographically
      distinct groups of neurons whose activation results in different forms of
      defensive or protective reactions. Reactions evoked from the lateral PAG column
      are associated with somatomotor and autonomic activation and are characteristic
      of an organism's response to superficial or cutaneous noxious stimuli, whereas
      reactions evoked from the ventrolateral PAG column are associated with
      somatomotor and autonomic inhibition and appear to correspond to an organism's
      response to deep or visceral noxious stimuli. Furthermore, the neurons of these
      two columns possess some degree of somatotopic and viscerotopic organization and
      send axon collaterals to multiple targets in the medulla. This model of PAG
      neuronal organization outlines the basic architectural features of a network
      involved in the coordinated expression of certain types of defensive/protective
      reactions.

PMID- 8136049
TI  - Mechanisms of defense in the inferior colliculus.
AB  - The inferior colliculus (IC) is a well known relay station for auditory pathways
      in the brainstem. In the present review we are suggesting that aversive states
      are also generated and elaborated in the inferior colliculus and that this
      structure may be part of a brain system commanding defensive behavior. The
      evidences presented in this review have been obtained from experiments carried
      out with the combined use of intracerebral microinjections and of electrical
      stimulation of the inferior colliculus. This electrical stimulation caused a
      behavioral activation together with autonomic reactions usually observed as part
      of the defense reaction. NMDA--an excitatory amino acid--, or bicuculline--a
      GABAA antagonist--injected into the IC mimicked the effects of its electrical
      stimulation. The IC electrical stimulation showed clear aversive properties as
      rats submitted to a switch-off paradigm quickly learned to interrupt it. Systemic
      administration as well as IC microinjections of the anxiolytic compound midazolam
      caused dose-dependent increases in the latency and reductions in the frequency of
      switch-off responses to the inferior colliculus electrical stimulation. Similar
      results were obtained following microinjections into this brainstem structure of
      the GABAA agonist muscimol. These results suggest that neural substrates
      responsible for defensive behavior in the inferior colliculus may be depressed by
      benzodiazepines as part of the anxiolytic action of these compounds. This anti
      aversive action may be produced by the enhancement of GABAA mechanisms.
      Serotonergic mechanisms seem also to be involved in the modulation of these
      aversive states as IC microinjections of zimelidine, a 5-HT uptake blocker,
      caused a significant inhibition of the switch-off responses in the shuttle
      box.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136050
TI  - Midbrain substrates of audiogenic seizures in rats.
AB  - Audiogenic seizures (AS) are a rodent model of generalized tonic-clonic seizures,
      induced in susceptible (S) animals by high intensity (110 dB) acoustic
      stimulation. Resistant (R) animals do not respond to the sound with any seizure
      related behavior, but they display facial automatisms and grooming clusters.
      Genetic selection and neuroethology are the basic tools used in our laboratory to
      perform behavioral analysis of AS S and R animals. Based upon selective lesion
      and microinjection (GABA, clobazam, NMDA) studies of substantia nigra (SN),
      inferior colliculus (IC), superior colliculus (SC), and on specific knife cuts at
      midcollicular levels, we have suggested differential roles for these substrates
      in the origin and spreading of AS. The IC central nucleus is suggested to be the
      most critical area involved in the afferent pathway whose activation is necessary
      for AS origin. IC cortical nuclei seem to be the most important structures
      involved in the transduction of sensory to motor activity. SC, SN and other
      reticular subnuclei are suggested to be modulators or components of the efferent
      pathway. Although the midbrain is considered to be the only network necessary for
      acute AS origin, both emotion-linked acoustic memories and plastic changes linked
      to audiogenic kindling involve midbrain-forebrain connections. This paper reviews
      the behavioral manifestations of acute and chronic AS, our contribution to the
      knowledge of some AS neurobiological midbrain substrates and the suggested
      implications of midbrain-forebrain interactions typical of AS kindling.

PMID- 8136051
TI  - Emotional memory systems in the brain.
AB  - The neural mechanisms of emotion and memory have long been thought to reside side
      by side, if not in overlapping structures, of the limbic system. However, the
      limbic system concept is no longer acceptable as an account of the neural basis
      of memory or emotion and is being replaced with specific circuit accounts of
      specific emotional and memory processes. Emotional memory, a special category of
      memory involving the implicit (probably unconscious) learning and storage of
      information about the emotional significance of events, is modeled in rodent
      experiments using aversive classical conditioning techniques. The neural system
      underlying emotional memory critically involves the amygdala and structures with
      which it is connected. Afferent inputs from sensory processing areas of the
      thalamus and cortex mediate emotional learning in situations involving specific
      sensory cues, whereas learning about the emotional significance of more general,
      contextual cues involves projections to the amygdala from the hippocampal
      formation. Within the amygdala, the lateral nucleus (AL) is the sensory interface
      and the central nucleus the linkage with motor systems involved in the control of
      species-typical emotional behaviors and autonomic responses. Studies of cellular
      mechanisms in these pathways have focused on the direct relay to the lateral
      amygdala from the auditory thalamus. These studies show that single cells in AL
      respond to both conditioned stimulus and unconditioned stimulus inputs, leading
      to the notion that AL might be a critical site of sensory-sensory integration in
      emotional learning. The thalamo-amygdala pathway also exhibits long-term
      potentiation, a form of synaptic plasticity that might underlie the emotional
      learning functions of the circuit. The thalamo-amygdala pathway contains and uses
      the amino acid glutamate in synaptic transmission, suggesting the possibility
      that an amino-acid mediated form of synaptic plasticity is involved in the
      emotional learning functions of the pathway. We are thus well on the way to a
      systems level and a cellular understanding of at least one form of emotional
      learning and memory.

PMID- 8136052
TI  - What brain structures are active during emotions? Effects of brain stimulation
      elicited aversion on c-fos immunoreactivity and behavior.
AB  - Aversive behavior is produced by stimulating some brain structures, such as the
      dorsal periaqueductal gray and the medial hypothalamus. We have used c-fos
      immunoreactivity to map brain areas which are influenced by stimulation of these
      two structures. Stimulation was produced in freely moving rats by electrical
      stimulation or by microinjections of either excitatory amino acids or GABA
      blocking drugs. Behavior was monitored to detect emotional changes. The effects
      on labeling induced by the stimulation of either structure were then compared.
      Structures labeled include the amygdala, the stria terminalis, the supramamillary
      area, the hypothalamus, the periaqueductal gray, the superior colliculus, the
      nucleus cuneiformis, and the locus coeruleus. Regardless whether chemical or
      electrical stimulation was used or the structure stimulated, there was a large
      overlap among the brain areas labeled. We then compared our results with data
      from the literature where other methods of inducing aversion have been used,
      including pain and stress. There was remarkable similarity in the patterning of
      labeling irrespective of the type of stimulation (central-peripheral, chemical
      electrical). There was, however, one interesting difference produced by central
      vs. peripheral stimulation. Labeling was unilateral in the former case and
      bilateral in the latter case. Our results suggest that there is a neural
      substrate that mediates aversive behavior, no matter how it is produced.
      Nevertheless, that peripheral stimulation produces mainly bilateral activation of
      this substrate whereas central stimulation produces mainly unilateral activation
      suggests that natural peripheral stimuli are also integrated at a higher
      functional level. Future work could be directed toward explicit comparisons of
      central versus peripheral stimulation to identify the structures involved in
      higher level integration of aversive behavior.

PMID- 8136053
TI  - Localization in the amygdala of the amnestic action of diazepam on emotional
      memory.
AB  - It is well known that systemically administered benzodiazepines (BZDs) induce
      anterograde amnesia in a variety of learning tasks. BZs effects are mediated
      through the GABAA complex by enhancing GABA-induced synaptic inhibition. As the
      GABAergic system in the amygdaloid complex (AC) is a site of action for the
      anxiolytic effects of BZs, such findings suggest that BZs may also influence
      memory through the amygdala. The present report summarizes a recent series of
      experiments designed to examine this implication. In a first experiment rats
      received either sham or bilateral AC lesion using N-methyl-D-aspartic acid
      (NMDA). One week later, animals were trained on an inhibitory avoidance task and
      tested 48 h later. Diazepam (DZP; 1.0 and 2.0 mg/kg, i.p.) or vehicle was
      injected 30 min prior to acquisition. The results demonstrate that DZP-induced
      retention deficits was blocked in rats with AC lesions. In a second experiment,
      in an attempt to localize the site of BZDs amnestic action in the AC, we tested
      the effects of DZP in rats with bilateral ibotenic acid-induced lesions of
      central (CE), lateral (LAT) or basolateral (BL) amygdala nuclei. The results
      shown that retention was impaired in animals with CE and LAT lesions but not in
      animals with BL lesions. In a third experiment we tested the effects of DZP
      microinjections in different nuclei of the AC on retention performance of rats
      trained in an avoidance task. The results demonstrate that DZP microinjection
      prior training in the BL/LAT, but not CE nuclei produce anterograde
      amnesia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136054
TI  - Parabrachial nucleus lesions and conditioned taste aversion: evidence supporting
      an associative deficit.
AB  - Three experiments examined the conditioned taste aversion (CTA) deficit that
      occurs following electrolytic lesions of the parabrachial nucleus (PBN). In
      Experiment 1, lesioned rats failed to avoid either a gustatory or an olfactory
      stimulus that had been paired with lithium chloride-induced toxicosis. In
      Experiment 2, however, all rats learned a conditioned flavor preference. Finally,
      in Experiment 3, all controls and 7 of the 12 lesioned rats learned a conditioned
      place aversion. Together, these results demonstrate that the disruption of CTA in
      lesioned rats cannot be ascribed to an inability to process either gustatory or
      visceral afferent information per se. Rather, the data suggest that PBN-lesioned
      rats are unable to form a specific association between gustatory and visceral
      cues.

PMID- 8136055
TI  - Learning-induced plasticity in the medial geniculate nucleus is expressed during
      paradoxical sleep.
AB  - Fear conditioning to an acoustic stimulus produces increases in tone-evoked
      discharges of neurons in the medial division of the medial geniculate nucleus
      (MG). This study examined the responses of MG neurons to a conditioned tone
      presented in paradoxical sleep (PS). After 1 session of habituation to a tone,
      awake rats underwent conditioning in 3 sessions during which the tone was used as
      the conditioned stimulus preceding a footshock. Control rats received unpaired
      presentations of tone and shock. The same tone, which never awakened the animal,
      was presented during PS following each daily session. Responses of MG neurons to
      the tone in PS were increased after conditioning. This enhancement was as large
      as that in waking and was manifested earlier after tone onset than in waking. No
      change appeared after pseudoconditioning. These results demonstrate that
      associatively induced plasticity in the MG can be expressed during PS.

PMID- 8136056
TI  - Nucleus basalis magnocellularis and attention: effects of muscimol infusions.
AB  - The basal forebrain is important in cognitive processing. Most studies have
      focused on the importance of this area in mnemonic processing. However, the
      nucleus basalis magnocellularis (NBM), which is a major component of the basal
      forebrain, may also be involved in attentional processes. Attention can influence
      the sensitivity of perceptual processes, as assessed by discriminability, or the
      selection of response strategies, as assessed by bias. This experiment examined
      whether temporary inactivation of the NBM, using the GABA agonist muscimol, would
      interfere with attention. Each rat was tested in a 2-choice reaction time (RT)
      task in which stimulus frequency was varied. RT and error rate increased, and
      discriminability decreased following muscimol infusions into the NBM. Bias was
      unchanged. The pattern of results provides evidence that the NBM is important in
      attention, and this influence of the NBM acts primarily on perceptual aspects of
      attention.

PMID- 8136058
TI  - Organization of partner preference and sexual behavior and its nocturnal
      rhythmicity in male rats.
AB  - Male rats were neonatally treated with 1,4,6-androstatriene-3,17-dione (ATD),
      which blocks aromatization of testosterone (T) to estradiol (E2), from Days 0, 2,
      or 5 through 14. Adult partner preference behavior (PPB; choice between estrous
      female rat [F] and active male rat [M]) was studied in the early part of the dark
      phase of the light-dark (LD) cycle. ATD Day 0 Ms showed a preference for the
      stimulus M or showed no preference for either of the stimulus Ss. Controls
      preferred the estrous F. ATD Days 2 and 5 Ms showed PPB intermediate between ATD
      Day 0 Ms and controls. Thus the neonatally sensitive period for organization of
      adult PPB extends beyond Day 5. Furthermore, PPB showed a nocturnal rhythmicity
      in ATD Ms but not in controls. In the late part of the dark phase, all Ms showed
      a preference for the stimulus F. ATD Days 2 and 5 Ms and control Ms were no
      longer different in PPB, but ATD Day 0 Ms still showed significantly lower
      preference scores for F than all other Ms. Thus the E2 metabolite of T suppresses
      organization of an adult nocturnal rhythm in PPB.

PMID- 8136057
TI  - Pavlovian conditioning of heart rate and body temperature with morphine: effects
      of CS duration.
AB  - Rats were exposed to a conditioning procedure that varied the duration of overlap
      between a light-noise conditioned stimulus (CS) and the effects of a morphine (5
      mg/kg) unconditioned stimulus (US). Three paired (P) groups differed in CS
      duration (5, 15, or 60 min) but had the same CS-US interval (30 s). A control
      group (U) received explicitly unpaired presentations of CS and US. P groups
      showed CS-specific attenuation of the bradycardic response and enhancement of the
      hyperthermic response to morphine. During placebo tests, the CS elicited
      conditioned increases in heart rate and body temperature in Groups P15 and P60.
      Group P5 showed a conditioned increase in heart rate but not in body temperature.
      Overall, strength of conditioning was directly related to CS duration. These data
      indicate that duration of overlap between a CS and drug-induced changes in a
      target response system is an important determinant of Pavlovian drug
      conditioning.

PMID- 8136059
TI  - Mitigating effects of combined prenatal and postnatal exposure to ethanol on
      learned persistence in the weanling rat: a replication under high-peak
      conditions.
AB  - Replicating an earlier report under low-peak blood ethanol concentration (BEC)
      conditions, weanling rats, exposed in utero or postnatally to levels of ethanol
      that resulted in high-peak BECs, showed an attenuated partial reinforcement
      extinction effect, whereas pups exposed both pre- and postnatally did not differ
      from controls. Also supporting earlier work, postnatal exposure resulted in
      significantly reduced brain weight and had effects on hippocampal measures. These
      results from the combined-exposure group, along with earlier work, point to a
      possible mitigating influence in the rat of prenatal exposure to ethanol on the
      behavioral effects of postnatal exposure. They suggest that a protective factor
      may be operating, akin to the proactive immunoreactive effects of heat shock
      proteins shown in recent work at the cellular and hippocampal levels.

PMID- 8136060
TI  - Behavioral effects of methylazoxymethanol-induced micrencephaly.
AB  - This study was prompted by reports of functionally normal humans with
      micrencephaly or cortical hypoplasia. Methylazoxymethanol acetate (MAM)
      treatment, which induces micrencephaly in rats, was administered by injection (20
      mg/kg) on gestational day 14. Prior to weaning and into adulthood, offspring were
      assessed on many behavioral tests. There were 3 findings. First, MAM rats
      (forebrain weight less than 2/3 of controls) were not profoundly hyperactive.
      Increased activity was seen only on prolonged tests or after amphetamine
      administration. Second, MAM rats were hypoactive in some conditions. These rats
      were light shy and less likely to explore lighted areas. MAM rats appeared
      hyperreactive to environmental stimuli, but not hyperactive. Finally, no MAM
      effect on behavior was as large as that on brain weight. Thus, as with clinical
      findings, rat micrencephalics are more remarkable for functional sparing than for
      behavioral abnormalities.

PMID- 8136061
TI  - Rewarding brain stimulation: role of tegmental cholinergic neurons that activate
      dopamine neurons.
AB  - Cholinergic neurons of the pedunculopontine nucleus (Ch5) are believed to
      monosynaptically excite ventral tegmental dopamine neurons. Muscarinic blockers
      injected near dopamine cells block the rewarding effect of hypothalamic or dorsal
      tegmental rewarding brain stimulation (RBS) in rats. Because Ch5 cells are
      inhibited by muscarinic agonists, we injected muscarinic drugs unilaterally near
      Ch5 neurons to inhibit or disinhibit them. Carbachol raised thresholds for
      hypothalamic self-stimulation bilaterally by over 400%, whereas scopolamine
      reduced thresholds by 20%-80%. Pretreatment with either carbachol or scopolamine
      blocked the effect of the other drug, which suggests that both acted through the
      same receptors near Ch5 cells. Therefore, activation of Ch5 neurons is critical
      for hypothalamic RBS. A mechanism for the involvement of Ch5 neurons in drug
      rewards and antimuscarinic psychosis is also proposed.

PMID- 8136062
TI  - Lack of a temporal gradient of retrograde amnesia in rats with amygdala lesions
      assessed with the fear-potentiated startle paradigm.
AB  - It is well known that lesions of the hippocampal formation produce a temporally
      graded retrograde amnesia for certain types of memory. A similar pattern of
      results has been reported with amygdaloid lesions in avoidance learning (K.C.
      Liang et al., 1982). The present study examined the effects of posttraining
      amygdaloid lesions using a Pavlovian conditioning task, fear-potentiated startle,
      in which the amplitude of the acoustic startle reflex is increased when elicited
      in the presence of a cue (e.g., a light) previously paired with footshock.
      Electrolytic lesions of the amygdala given either 6 or 30 days after training
      blocked the expression of potentiated startle, indicating no temporal gradient of
      amnesia over these intervals in this paradigm. The effects of amygdaloid lesions
      on different measures of aversive learning are discussed.

PMID- 8136063
TI  - Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and
      long-term contextual fear.
AB  - The effects of amygdala, hippocampus, and periaqueductal gray (PAG) lesions on
      contextual fear conditioning in rats were examined. Freezing behavior served as
      the measure of conditioning. Unlesioned control animals showed reliable
      conditional freezing in the testing chamber when observed both immediately and 24
      hr after footshocks. In contrast, rats with amygdala or ventral PAG lesions
      exhibited a significant attenuation in freezing both immediately and 24 hr after
      the shocks. Dorsal PAG lesions had no effect on freezing at either time. Animals
      with hippocampal lesions displayed robust freezing behavior immediately following
      the shock, even though they showed a marked deficit in freezing 24 hr after the
      shock. These results indicate that there are anatomically dissociable short- and
      long-term conditional fear states.

PMID- 8136064
TI  - Noninteractive effects of diazepam and amygdaloid lesions in two animal models of
      anxiety.
AB  - The role of the amygdala in mediating the anxiolytic effects of diazepam was
      examined in two models of rat anxiety. As in our previous experiments, amygdaloid
      lesions by themselves did not increase rats' exploration of the open arms of the
      elevated plus-maze or decrease rats' burying of an electrified probe in the shock
      probe burying test. However, amygdaloid lesions did increase rats' shock-probe
      contacts. Diazepam (2 mg/kg) increased open-arm activity and decreased burying
      behavior to an equal extent in sham-lesioned and amygdala-lesioned rats and had
      no significant effect on the facilitation of probe contacts induced by amygdaloid
      lesions. These results suggest that many of the anxiolytic effects of
      benzodiazepines are not mediated by the amygdala.

PMID- 8136065
TI  - Lateralized response to diazepam predicts temperamental style in rhesus monkeys.
AB  - Based on previous findings in humans and rhesus monkeys suggesting that diazepam
      has asymmetrical effects on frontal lobe activity and other literature supporting
      a role for the benzodiazepine system in the mediation of individual differences
      in anxiety and fearfulness, the relation between asymmetrical changes in scalp
      recorded regional brain activity in response to diazepam and the temperamental
      dimension of behavioral inhibition indexed by freezing time in 9 rhesus monkeys
      was examined. Animals showed greater relative left-sided frontal activation in
      response to diazepam compared with the preceding baseline. The magnitude of this
      shift was strongly correlated with an aggregate measure of freezing time (r =
      .82). The implications of these findings for understanding the role of regional
      differences in the benzodiazepine system in mediating individual differences in
      fearfulness are discussed.

PMID- 8136066
TI  - Intact acquisition and long-term retention of mirror-tracing skill in Alzheimer's
      disease and in global amnesia.
AB  - The ability of patients with Alzheimer's disease (AD) or global amnesia (AMN) to
      acquire skill for tracing a pattern seen in mirror-reversed view and to retain
      that skill over 24-h intervals was examined. Both patient groups had poor recall
      and recognition of their mirror-tracing experience, but they acquired and
      retained mirror-tracing skill as well as normal control subjects. One AMN patient
      (H.M.) retained the skill over a year-long interval. Furthermore, the patients
      transferred their skill normally to an alternate pattern. These results indicate
      that the memory system underlying mirror-tracing skill learning is separable from
      medial-temporal structures compromised in AMN and AD and from neocortical areas
      compromised in AD. Brain regions relatively spared in early AD, such as the basal
      ganglia or cerebellum, may mediate critical aspects of the learning of novel
      sensorimotor associations that underlie skilled mirror tracing.

PMID- 8136067
TI  - Eyeblink classical conditioning in H.M.: delay and trace paradigms.
AB  - H.M., a well-known subject with bilateral removal of medial-temporal-lobe
      structures and profound amnesia, performed eyeblink classical conditioning (EBCC)
      for 21 90-trial sessions in the 400-ms delay and 900-ms trace paradigms. A 2nd
      amnesic subject with temporal lobe lesions and 2 normal control subjects (NCSs)
      were also conditioned. Acquisition occurred in both paradigms for all subjects.
      Acquisition in the delay paradigm was prolonged in H.M. (perhaps because of his
      cerebellar degeneration in the vermis and hemispheres), but not in the 2nd
      amnesic subject. Amnesic subjects and NCSs showed more rapid acquisition in the
      trace than in the delay paradigm. Two years after initial EBCC, H.M. attained
      learning criterion in the trace paradigm in 1/10th as many trials. No
      recollection of the experimenters, apparatus, instructions, or procedure was
      manifested by H.M. Results suggest that humans can condition in the 400-ms delay
      and 900-ms trace EBCC paradigms with the hippocampus radically excised.

PMID- 8136068
TI  - Effects of hyperglycemia on memory and hormone levels in dementia of the
      Alzheimer type: a longitudinal study.
AB  - The effect of hyperglycemia on hormone levels, metabolite levels, and memory
      performance was examined in 22 subjects with very mild and mild probable dementia
      of the Alzheimer type (DAT) and in 12 normal elderly adults. Subjects were tested
      in 3 plasma glucose conditions (fasting baseline, 175 mg/dl, and 225 mg/dl) at
      initial and 18-month follow-up sessions. Initially, adults with very mild DAT
      showed memory facilitation and elevations in plasma insulin in the 225-mg/dl
      glucose condition relative to baseline. At follow-up, very mild DAT patients
      whose dementia had progressed showed significant decreases in insulin and
      hyperglycemic memory facilitation. Changes in basal insulin and cortisol levels
      over time were correlated with memory changes for DAT subjects. These results
      suggest that glucoregulatory abnormalities may contribute to the pathophysiology
      of DAT.

PMID- 8136069
TI  - Using signaled barpressing tasks to study the neural substrates of appetitive and
      aversive learning in rats: behavioral manipulations and cerebellar lesions.
AB  - The development of standard within-subject conditioning tasks for studying
      similarities and differences in the neural substrates of appetitive and aversive
      learning is described. Rats learned to press a bar during a brief tone
      presentation to receive a food pellet reward (the appetitive task). Using the
      same tone signal, conditioning chamber, and trial timing parameters, the same
      rats were then trained to press the bar during the tone presentation to avoid a
      mild footshock (the aversive task). As an initial study of the neural substrates
      of these forms of learning, the involvement of the cerebellum was assessed.
      Bilateral lesions of the deep cerebellar nuclei prevented the learning of the
      aversive task but had no effect on the learning of the appetitive task.

PMID- 8136070
TI  - Reversible lesions of the nucleus of the solitary tract attenuate the memory
      modulating effects of posttraining epinephrine.
AB  - Rats implanted with cannula tips placed above the nucleus of the solitary tract
      (NTS) were trained to obtain food pellets placed in 2 arms of a Y maze and then
      given a footshock in 1 arm of the maze. The rats then received bilateral
      injections of lidocaine or buffer into the NTS and peripheral injections of
      saline or epinephrine (0.01 or 0.05 mg/kg ip). Two tests were given 24 and 48 hr
      after training to assess retention in the presence and absence of contextual cues
      (the stainless steel floor) associated with the footshock training trial.
      Epinephrine (0.05 mg/kg) produced a significant enhancement in retention, which
      was attenuated by injections of lidocaine into the NTS. These findings indicate
      that the NTS is involved in mediating the memory-modulating effects of peripheral
      epinephrine and that such effects are initiated at least in part by activation of
      vagal afferents projecting to the NTS.

PMID- 8136071
TI  - Conditioned opioid activity in the rat fetus.
AB  - Classical conditioning in the rat fetus (Embryonic Day 20) was investigated in 4
      experiments. Reexposure to a conditioned stimulus (CS; sucrose), after 3 pairings
      with an unconditioned stimulus (US; milk), reduced fetal facial wiping in a
      bioassay of perioral cutaneous responsiveness. Reduced responsiveness was evident
      only in subjects that received paired presentations of the CS and US and cannot
      be attributed to habituation, sensitization to the CS, or protracted effects of
      US exposure during conditioning trials. Fetuses attended to the chemosensory, not
      the tactile, qualities of the sucrose infusion during CS reexposure. Changes in
      fetal responsiveness resulted from conditioned activity in the endogenous opioid
      system, specifically at mu opioid receptors. These data confirm that the rat
      fetus is capable of exhibiting a conditioned opioid response in utero.

PMID- 8136073
TI  - Acoustic startle response and habituation in freezing and nonfreezing rats.
AB  - Rats can be divided according to their responses to startle-eliciting stimuli
      into 2 groups with different emotional states. About half of the 54 female
      Sprague-Dawley rats showed long-lasting freezing behavior after 1-8 stimuli (10
      kHz, 110 dB spl). In freezing rats the startle amplitude was higher than in
      nonfreezing rats, even on the very first startle response. This finding
      demonstrates that the anxiety state of these animals before the first startle
      eliciting stimulus, and not just the aversiveness of the stimulus, contributes to
      freezing behavior. In addition, in freezing rats there was no influence of
      spontaneous motor activity or of adaptation time on startle amplitude. Only in
      nonfreezing rats were high motor activities correlated with lowered startle
      amplitudes, and only in these rats did the course of startle habituation depend
      on adaptation time.

PMID- 8136072
TI  - Emotion, novelty, and the startle reflex: habituation in humans.
AB  - Previous research with both animal and human subjects has shown that startle
      reflex magnitude is potentiated in an aversive stimulus context, relative to
      responses elicited in a neutral or appetitive context. In the present experiment,
      the same pleasant, unpleasant, and neutral picture stimuli were repeatedly
      presented to human subjects. Startle reflex habituation was assessed in each
      stimulus context and was compared with the habituation patterns of heart rate,
      electrodermal, and facial corrugator muscle responses. All systems showed initial
      differentiation among affective picture contents and general habituation over
      trials. The startle reflex alone, however, continued to differentiate among
      pleasant, neutral, and unpleasant pictures throughout the presentation series.
      These results suggest that (a) the startle probe reflex is relatively
      uninfluenced by stimulus novelty, (b) the startle modulatory circuit (identified
      with amygdala-reticular connections in animals) varies systematically with
      affective valence, and (c) the modulatory influence is less subject to
      habituation than is the obligatory startle pathway or responses in other somatic
      and autonomic systems.

PMID- 8136074
TI  - Comparison of the short- and long-lasting effects of perforant path kindling on
      radial maze learning.
AB  - The present experiment compared the long-lasting with the short-lasting effects
      of kindling the perforant path input to the hippocampal formation on the
      acquisition of two radial maze tasks. Animals in the long-term group were fully
      kindled (i.e., Stage 5 motor seizures were evoked) prior to a stimulation-free
      training period. Animals in the short-term group were kindled 30-45 min prior to
      each learning trial. A third group of animals served as controls and were never
      kindled. On both 8-arm and 4/8-arm radical maze tasks, learning impairments were
      apparent only in the short-term group. Thus, the impaired learning is more likely
      related to the short-term aftereffects of an afterdischarge than to any long-term
      alterations in the neuronal status of the brain caused by kindling.

PMID- 8136075
TI  - Ibotenate lesions of the hippocampus enhance latent inhibition in conditioned
      taste aversion and increase resistance to extinction in conditioned taste
      preference.
AB  - In 2 experiments, the effects of axon-sparing lesions of the hippocampus on
      performance in aversive and appetitive taste conditioning tasks were
      investigated. In Experiment 1, hippocampally lesioned rats showed no impairment
      of conditioned taste aversion learning relative to control subjects, but they did
      display an increased sensitivity to latent inhibition (LI). In Experiment 2, the
      same hippocampectomized rats acquired a conditioned taste preference but failed
      to show any evidence of extinction. The influence of the neurotoxic lesion on LI
      is in the opposite direction to the effect typically found following hippocampal
      damage induced by traditional methods. Accordingly, the data present challenges
      for most current theories of hippocampal function.

PMID- 8136076
TI  - Identification of the NADPH-binding protein of the neutrophil superoxide
      generating oxidase of guinea pigs.
AB  - A cell-free system prepared from polymorphonuclear neutrophils is capable of
      NADPH-dependent generation of superoxide anion, but requires the simultaneous
      presence of plasma membranes, cytosol, arachidonate and guanosine 5'-[gamma
      thio]triphosphate (GTP[S]). The isolated membranes from such a preparation are
      able to catalyse NADPH-dependent superoxide formation independently of added
      cytosol and activators. Such activated membranes, activated in the cell-free
      system, must consequently contain all of the essential components required by the
      oxidase for superoxide formation, including the NADPH-binding component.
      Arylazido-beta-alanyl-[32P]NADPH (3'-O-(3-[N-(4-azido-2-nitrophenyl)-amino]
      propionyl)-[32P]NADPH), an NADPH analogue and photoaffinity probe, is shown to
      act in the dark as a substrate for the oxidase activity in the activated
      membranes and an irreversible photodependent inhibitor following
      photoirradiation. The photoaffinity probe has been used to identify the specific
      NADPH-binding component of the oxidase in the activated membranes. In contrast
      with the sensitivity of the activated membranes, photoirradiation of arylazido
      beta-alanyl-[32P]-NADPH under identical conditions, but with non-activated
      membranes, did not prevent subsequent activation of the treated membranes by
      cytosol, arachidonate and GTP[S]. However, photoirradiation of the cytosolic
      fraction in the presence of arylazido-beta-alanyl-[32P]NADPH resulted in an
      inhibition of the cytosol's ability to activate superoxide generation upon
      subsequent incubation with plasma membranes in the presence of arachidonate and
      GTP[S]. These observations are taken as a strong indication that the NADPH
      binding protein of the oxidase is a cytosolic factor which associates with the
      plasma membrane upon activation. The superoxide-generating activity of the
      activated membranes was inhibited irreversibly in a concentration- and photo
      dependent manner by arylazido-beta-alanyl-NADPH. The arylazido-beta-alanyl-NADPH
      photodependent inhibition of superoxide generation in the activated membranes
      correlated with the photodependent labelling of a protein of 55.6 kDa by the
      arylazido-beta-alanyl-NADPH. Specificity of labelling was indicated by a lack of
      labelling of the 55.6 kDa region in the non-activated membranes and protection of
      the photodependent inhibition and labelling of the 55.6 kDa protein by NADPH. It
      is proposed that the arylazido-beta-alanyl-NADPH-labelled 55.6 kDa protein
      present on the activated membranes is the NADPH-binding protein of the neutrophil
      superoxide-generating oxidase.

PMID- 8136077
TI  - Bovine pancreatic deoxyribonuclease F: isoelectric focusing, peptide mapping and
      primary structure.
AB  - DNAase F is a minor isoform of bovine pancreatic DNAase which can be separated
      from the other isoforms (DNAases A, B, C and D) present in a commercial
      preparation by a preparative isoelectric-focusing cell (Rotofor; Bio-Rad). The
      ampholytes and other contaminating proteins present in DNAase F preparations can
      be removed by chromatography on an affinity column (Cibacron Blue 3GA-agarose)
      and a hydrophobic-interaction column (phenyl-Sepharose CL-4B). The complete
      separation of DNAase F from the other isoforms is demonstrated on a thin-layer
      isoelectric-focusing gel, DNAase F being the most basic (pI 5.68). A procedure is
      described for tryptic peptide mapping by h.p.l.c. requiring only picomolar
      amounts of DNAase F protein. The DNAase F map shows two peptide peaks not present
      in the DNAase A map, and the DNAase F map does not have a peak at the position
      where a C-terminal peptide of DNAase A is normally eluted. The amino acid
      compositions and sequences for the two new peptides suggest that Gly240 in DNAase
      A is changed to Arg240 in DNAase F.

PMID- 8136078
TI  - Towards an understanding of structure-function relationships of elongation factor
      Tu.
AB  - In light of the recently determined structure of elongation factor Tu, and taking
      into account chemical studies mapping functional sites, a number of residues have
      been selected for site-directed mutagenesis studies. Gly94, Gly126, His66,
      His118, Lys89 and Asp90 have each been point-mutated. Preliminary in vitro
      characterization data are presented.

PMID- 8136079
TI  - The involvement of extracellular proteinases and proteinase inhibitors in
      mammalian fertilization.
AB  - Extracellular proteinases and proteinase inhibitors have been known to play many
      important roles in various biological systems. They are also important for
      reproductive functions of the mammals. Kallikrein stimulates human sperm
      motility. Porcine antithrombin III (AT III) has been identified to be a sperm
      motility-stimulating protein and a chemoattractant for boar sperm. AT III
      immunoreactive molecules are also detected on the zona pellucida of ovulated
      porcine eggs and are suggested to act as a sperm receptor. Proteinase inhibitors
      in the seminal plasma act as decapacitation factors. Both the proteinase
      inhibitors in the seminal plasma and the trypsin-like protein(s) on the surface
      of the sperm head play important roles in the sperm-egg interaction. The trypsin
      like protein(s) are also involved in the induction of acrosome reaction.
      Plasminogen activator was demonstrated to be a trigger of the zona reaction. In
      summary, the roles of extracellular proteinases and proteinase inhibitors in the
      mammalian fertilization process are diversified and worthy of further
      investigation.

PMID- 8136080
TI  - Plant low-molecular-mass heat-shock proteins: their relationship to the
      acquisition of thermotolerance in plants.
AB  - Among the heat-shock proteins (HSPs) induced in response to heat-shock (HS) in
      all organisms, the low-molecular-mass (LMM) HSPs are the most abundant and unique
      in plants. The HSP genes at the transcriptional and the translational levels have
      been well-characterized; however, relatively little is known about the
      physiological function of HSPs. We have been studying the biological role of
      plant LMM HSPs based on the suggestion by Minton, Karmin, Hahn and Minton ([1982]
      Proc. Natl. Acad. Aci. U.S.A. 79, 7107-711) that HSPs may act as heat-stable
      proteins to non-specifically stabilize other proteins which are highly
      susceptible to inactivation or denaturation by heat. For the future, LMM-HSP gene
      transfer into organisms that do not synthesize plant LMM HSPs would be a way of
      determining the function of LMM HSPs, and success could be of practical
      importance.

PMID- 8136081
TI  - An immobilized-enzyme system for the determination of sialic acid using cloned
      neuraminidase from Clostridium perfringens A.T.C.C. 10543.
AB  - Neuraminidase expressed by cloned nanH of Clostridium perfringens has been
      immobilized and employed to determine the concentration of sialic acid in human
      serum. Two enzyme pairs, cloned neuraminidase-N-acetylneuraminate (NANA) lyase
      and pyruvate oxidase-peroxidase, have been respectively co-immobilized on to 1,12
      aminododecane-agarose with glutaraldehyde. The relative specific activities of
      the co-immobilized neuraminidase and NANA lyase were 61 and 77%, and those of
      pyruvate oxidase and peroxidase were 51 and 96% of the corresponding soluble
      enzymes respectively. The optimal reaction pH at 37% C for each of the co
      immobilized enzymes was about 1 pH unit higher than that of the corresponding
      soluble enzyme. The optimal reaction temperature of peroxidase was increased as a
      result of immobilization. The thermostability of the immobilized cloned
      neuraminidase, NANA lyase, pyruvate oxidase and peroxidase were increased 80-, 83
      , 115- and 147-fold at 45 degrees C over the soluble forms respectively. The
      results correlated satisfactorily with those obtained by using a soluble enzyme
      system. The system is thus a reliable assay method for sialic acid in serum.

PMID- 8136082
TI  - Isolation and characterization of a toxic phospholipase A2 from the venom of the
      Taiwan habu (Trimeresurus mucrosquamatus).
AB  - A toxic phospholipase A2 (PLA2) was isolated from Taiwan-habu-snake (Trimeresurus
      mucrosquamatus) venom by sequential chromatographies on CM-52, Sephadex G-75 and
      S-Sepharose columns. This basic PLA2 has a single polypeptide with an estimated
      M(r) of 15,000. The PLA2 activity was Ca(2+)-dependent and inactivated by p
      bromophenacyl bromide and its specific antibody. The toxic PLA2-induced myotoxic
      and direct haemolytic effects as well as respiratory distress in mice with an
      intraperitoneal LD50 of 1.17 micrograms/g body weight. The histological
      examination showed it caused haemorrhage and congestion in the viscera of mice.
      It was also cytotoxic to myeloma cells (NS-1), baby-hamster-kidney (BHK) cells
      and human umbilical endothelial cells. By neutralization experiments with a
      specific antibody against toxic PLA2, it was found that the enzymic activity of
      toxic PLA2 is essential for its myotoxicity, but it is not the only factor
      responsible for the lethal toxicity.

PMID- 8136083
TI  - Taxon-specific lens crystallins with endogenous enzymic activities: some
      perspectives on synthetic applications.
AB  - A systematic and general approach has been carried out to provide basic
      structural and mechanistic information on epsilon- and delta-crystallin with
      lactate dehydrogenase and argininosuccinate lyase activities respectively from
      representative species of birds. A detailed kinetic analysis of these two
      crystallins revealed considerable differences in the enzymic activities among
      different species of birds. Especially noteworthy is the abundant presence of
      high activity in duck and goose epsilon- and delta-crystallins in contrast with
      the total lack of epsilon-crystallin and diminished activities of delta
      crystallins in chicken and pigeon lenses. Sequence comparison of inactive pigeon
      delta-crystallin and active duck crystallin revealed several sequence variations
      and replacements which may account for the loss of argininosuccinate lyase
      activity in the lenses of certain birds. Bio-organic synthesis based on epsilon-
      and delta-crystallins isolated from duck lenses provides an efficient and
      practical tool for asymmetric or enantioselective synthesis of some
      pharmaceutically important chiral intermediates which may open new avenues and
      potentials in crystallin research.

PMID- 8136084
TI  - Tamoxifen in the prevention of breast cancer. Are the risks likely to outweigh
      the benefits?

PMID- 8136086
TI  - Adverse effects of drugs used in the management of constipation and diarrhoea.
AB  - Most laxatives, if used intermittently in the absence of contraindications, are
      relatively safe. Bulking agents may diminish absorption of some minerals and
      drugs, but this is not usually clinically significant. Ispaghula can cause
      serious allergic reactions. The chronic ingestion of stimulant laxatives has been
      blamed for the development of the 'cathartic colon', but there are no definitive
      studies which have demonstrated this. Dantron (danthron) preparations should only
      be used in older patients and the terminally ill because of the risk of
      hepatotoxicity with this drug. Oral oxyphenisatine should no longer be used.
      Senna would appear to be the stimulant laxative of choice during pregnancy and
      lactation. Bisacodyl is the polyphenolic derivative of choice. Lactulose,
      sorbitol and lactilol rarely cause significant adverse effects. Magnesium salt
      laxatives and phosphate enemas can cause serious metabolic disturbances in babies
      and young children. Liquid paraffin is contraindicated if there is any risk of
      aspiration. Interference with the absorption of fat soluble vitamins would not
      appear to be clinically significant. Docusate sodium may potentiate the
      hepatotoxicity of other drugs, but reports of this are rare. The role of
      cisapride in constipation has not been established. Antidiarrhoeal drugs are
      second line drugs whose use is aimed at minimising inconvenience and discomfort.
      No antidiarrhoeals can be recommended for children under 4 years of age.
      Loperamide is the drug of choice in older children and adults. The atropine
      component of diphenoxylate/atropine combinations can cause significant adverse
      effects. Bismuth salicylate is an inconvenient treatment for travellers'
      diarrhoea as large frequent doses of the liquid formulation are needed. Some
      bismuth can be absorbed and there is the potential to cause encephalopathy.
      Octreotide, methysergide and cholestyramine have a role for specific causes of
      diarrhoea only. Octreotide is effective in high output states from the small or
      large bowel, with few adverse effects. Clonidine and lidamidine may have a role
      in the treatment of chronic diabetic diarrhoea. The role of lidamidine in
      nondiabetic chronic diarrhoea has not been established.

PMID- 8136085
TI  - Comparative tolerability profiles of the newer versus older antidepressants.
AB  - Although the standard tricyclic antidepressants (TCAs) are generally effective in
      the treatment of depression, they can cause several troublesome adverse effects.
      Chief among these are their anticholinergic actions, which range from annoying
      dryness of the mouth and constipation to potentially dangerous urinary retention
      and confusion or delirium in the ill and elderly. Cardiovascular effects of TCAs
      include orthostatic hypotension, tachycardia and cardiac conduction slowing. Many
      TCAs are sedating and promote weight gain. Also problematic is the potential
      lethality of TCAs in overdose. The continual introduction of a host of new
      antidepressants over the past 15 years has provided an opportunity to improve the
      benefit-risk ratio for many patients by reducing medication-related toxicity.
      Selective serotonin reuptake inhibitors (SSRIs) and amfebutamone (bupropion),
      among others, are examples of effective antidepressants free of tricyclic-like
      anticholinergic, cardiovascular, sedating and appetite/weight-increasing effects.
      However, the new-generation drugs also present adverse effects of their own,
      including gastrointestinal distress, agitation and drug-drug interactions in the
      case of the SSRIs, and the risk of seizures or psychosis in amfebutamone
      recipients. Monoamine oxidase (MAO) inhibitors have also been refined; reversible
      inhibitors of MAO-type A afford protection against the usually feared
      hypertensive reaction to indirect sympathomimetic substances. The availability of
      new-generation antidepressants thus increases the likelihood of clinical response
      with a reduction in unwanted toxicity.

PMID- 8136087
TI  - Safety considerations in assessing the role of immunotherapy in allergic
      disorders.
AB  - Specific immunotherapy (SIT) is accepted as an effective treatment of allergic
      diseases when high quality extracts are used. However, this form of treatment can
      cause untoward reactions among which systemic reactions are the most severe.
      Although life-threatening reactions are rare and deaths exceptionally reported,
      SIT should be prescribed by allergists to patients with well defined
      characteristics, and administered with care by (or under the close supervision
      of) physicians trained to deal rapidly with the reactions. Reactions with
      standardised extracts occur mostly during the dose increase phase but they can be
      prevented using adapted schedules and premedication. During maintenance
      injections or when vial batches are changed, standardised extracts of known shelf
      life usually result in a low rate of systemic reactions. Patients with asthma are
      more prone to develop systemic reactions, and allergens should not be
      administered to patients with a forced expiratory volume in 1 second (FEV1) under
      70% of predicted or in those who have unstable or symptomatic asthma. Systemic
      reactions may be observed with all allergens and allergenic preparations although
      it appears that high molecular weight extracts may be safer.

PMID- 8136088
TI  - Risk-benefit assessment of omeprazole in the treatment of gastrointestinal
      disorders.
AB  - For the treatment of duodenal and gastric ulcer and reflux oesophagitis,
      especially erosive oesophagitis, omeprazole has an advantage over histamine H2
      receptor antagonists because it heals significantly more patients significantly
      faster. Adverse effects have been observed during short term treatment with the
      same frequency as during treatment with H2-antagonists. Also, maintenance
      treatment with omeprazole of reflux oesophagitis is significantly superior to H2
      antagonist therapy. During long term treatment for up to 8 years no further drug
      related adverse effects have been observed. Moderate hypergastrinaemia occurs in
      some patients, especially if an omeprazole dosage of 40 mg/day is needed. A
      slight increase of the agyrophil (endocrine) cell volume density and an extension
      of micronodular hyperplasia in the oxyntic mucosa after several years of
      omeprazole treatment seem to be related to the severity of the corpus gastritis
      and not to drug-induced hypergastrinaemia, because similar changes have been
      observed in equal frequency in patients not receiving anti-secretory drugs.
      Theoretical arguments against long term treatment with potent acid-suppressing
      drugs, such as the possible consequences of gastric bacterial overgrowth or
      hypergastrinaemia, are not supported by clinical observations and epidemiological
      data and are, therefore, speculative.

PMID- 8136089
TI  - Advances in the critical care of poisoned paediatric patients.
AB  - Recent improvements in paediatric intensive care may potentially improve outcome
      for severely poisoned children. The application of advanced techniques of
      critical care to the poisoned paediatric patient encompasses a wide variety of
      therapeutic and technical innovations that are primarily directed towards support
      of the cardiopulmonary system and removal of toxins. New extracorporeal removal
      techniques such as continuous arterio-venous haemofiltration have not
      substantively increased our ability to remove toxins except in rare instances.
      Exotic techniques such as extracorporeal membrane oxygenation remain in the
      background for use in rare instances only, with little clear data on the relative
      risks and benefits of applying them.

PMID- 8136090
TI  - 4-Methoxy-1-[(1R,4S,5R)-8-phenyl-menthoxycarbonyl]pyridinium
      hexachloroantimonate, C23H30NO3+.SbCl6-.
AB  - The 4-methoxypyridinium and oxycarbonyl moieties are coplanar and approximately
      parallel to the phenyl ring. The latter is involved in a number of short
      intramolecular interactions with the pyridinium and the oxycarbonyl atoms.
      Crystal packing is characterized by the presence of hydrophobic and hydrophilic
      channels, the former consisting of phenylmenthyl groups and the latter of
      pyridinium and SbCl6- ions.

PMID- 8136092
TI  - Effects of captopril on sympathetic activity, lipid and carbohydrate metabolism
      in a model of obesity-induced hypertension in dogs.
AB  - Ten age-matched beagle dogs were kept on a high-fat diet and followed for 12
      weeks. During this period the animals were divided into two groups (n = 5),
      either with or without oral captopril treatment. Dogs were tested periodically
      for biochemical and clinical parameters, and at the end of the study animals were
      killed and thoracic aorta samples were obtained for histologic evaluation. From
      the third week, the captopril group presented significantly lower values of mean
      arterial pressure, plasma norepinephrine, and fasting glucose and cholesterol
      levels than those attained in the nontreated group. Furthermore, aorta samples
      from untreated animals showed profuse staining for fat content at the intima and
      adventitia layers, while this reaction was restricted to the outer layer in
      treated dogs. These data suggest that the beneficial effects of captopril therapy
      in this obesity-induced hypertension model could be based on blood pressure
      control, together with reduction of serum glucose, cholesterol, and sympathetic
      activity levels. In addition, captopril treatment could play a role in the
      retardation of the early stages of vascular atherogenetic lesion.

PMID- 8136091
TI  - Lateral diffusion and fatty acid composition in vascular smooth muscle membrane
      from stroke-prone spontaneously hypertensive rats.
AB  - We measured membrane fluidity and fatty acid composition in cultured vascular
      smooth muscle cells from stroke-prone spontaneously hypertensive and Wistar-Kyoto
      normotensive rats. Membrane fluidity was measured as a lateral diffusion of 5 N
      (octadecanoyl) aminofluorescein using fluorescence microscopy and fluorescence
      recovery after photobleaching. Fatty acid composition of membrane fractions was
      measured using high performance liquid chromatography. Lateral diffusion was
      significantly lower (the membrane had lower fluidity) in vascular smooth muscle
      cells from stroke-prone spontaneously hypertensive rats as compared to those
      cells isolated from Wistar-Kyoto reference strain. The ratio of arachidonic acid
      to total fatty acids was 0.058 +/- 0.007 in the plasma membrane from stroke-prone
      spontaneously hypertensive rats and 0.036 +/- 0.005 in that from Wistar-Kyoto
      rats, P = .005. Similarly, the ratios of arachidonic to oleic acid and
      arachidonic to palmitic acid were significantly greater in cells from stroke
      prone spontaneously hypertensive rats (P = .002 for difference in each ratio).
      These results show decreased lateral diffusion (decreased membrane fluidity) in
      vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats.
      This is associated with increased content of arachidonic acid, the major
      precursor of prostaglandins and other eicosanoids. We postulate that local
      changes in the unsaturated fatty acid composition related to arachidonic acid
      storage and release contribute to reduced membrane fluidity in stroke-prone
      spontaneously hypertensive rats.

PMID- 8136093
TI  - A comparison of the effects of nifedipine and verapamil on exercise performance
      in patients with mild to moderate hypertension.
AB  - Twenty-four patients completed a double-blind, randomized clinical trial
      comparing the effects of nifedipine GITS (N) and verapamil SR (V) on blood
      pressure (BP) control and exercise performance. After a 2-week placebo phase, all
      subjects had measurements of VO2max, maximal workload, and endurance time. They
      were then randomized to either N (30 to 90 mg/day) or V (240 to 480 mg/day) and
      retested when BPs had stabilized. At rest, N lowered systolic (S) BP by 12 mm Hg
      (P = .02 compared to baseline) and diastolic (D) BP by 11 mm Hg (P = .001). V
      lowered SBP by 8 mm Hg (P = .013) and DBP by 11 mm Hg (P = .002). Neither drug
      affected resting heart rate. V significantly decreased resting epinephrine (P =
      .05) and there was a tendency for V to reduce norepinephrine (P = .07) and
      dopamine (P = .08). N tended to increase plasma renin activity (P = .07). During
      graded cycle ergometry N, compared with placebo, significantly lowered DBP at all
      exercise levels (P = .011), but had no significant effect on heart rate (HR),
      SBP, or heart rate pressure product (HRPP). Pulse pressure (PP) was significantly
      increased (P = .045), which was most noticeable at high exercise levels. Compared
      with placebo, V caused a marked reduction of exercise HR (P < .001), which was
      more pronounced at high levels, SBP (P = .004), DBP (P = .004), mean arterial
      pressure (MAP) (P = .001), and HRPP (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136094
TI  - Peripheral vascular changes and ambulatory blood pressure profiles.
AB  - This study aimed to correlate blood pressure (BP) level assessed either by casual
      or by 24-h ambulatory BP monitoring and regional (calf and finger) blood flow and
      associated vascular resistance in subjects with low, intermediate, and high BP.
      In 75 subjects covering the range from low BP to normo- and hypertension, blood
      flow at calf and finger vessels were simultaneously measured using an ECG
      triggered venous occlusion plethysmograph. Correlations were calculated between
      regional blood flow or vascular resistance and BP defined from casual and from 24
      h ambulatory BP registrations, at rest, and after 3 min of arterial occlusion
      (reactive hyperemia). Correlations over the whole BP range, between calf and
      finger vascular resistances and BP, were highly significant both for casual
      (0.650 < r < 0.776) and for ambulatory (0.531 < r < 0.781) BP. The relations
      remained significant after adjustment for the age dependency of the blood
      pressure. At any BP level skin (finger) blood flow at rest and after arterial
      occlusion was higher than muscle (calf) blood flow. These data indicate that
      there is a progressive decrease in vasodilating capacity from low to high BP in
      both muscle and skin vessels. However, in the zone of borderline to moderate
      essential hypertensives, blood flow after 3 min arterial occlusion was already
      significantly decreased in the muscle circulation when compared to normotensives,
      while still maintained in the skin circulation.

PMID- 8136095
TI  - Urinary endothelin: a possible biological marker of renal damage.
AB  - Endothelin (ET) is a powerful vasoconstrictor peptide synthesized and secreted by
      the vascular endothelium. Significant amounts of ET are also produced by
      nonendothelial cells, mainly tubular-epithelial and mesangial cells. Large
      amounts of ET are found in the urine compared with the small amounts present in
      blood. Because most of the ET filtered from plasma is subject to degradation by
      neutral endopeptidase (EC 3.4.24.11) in the proximal tubule, urinary ET is
      probably of renal origin. The range of urinary ET excretion in healthy persons is
      20 to 90 ng/day. The excretion of endothelin is modulated by several mechanical
      and chemical stimuli such as angiotensin II, phenylephrine, radiocontrast media,
      cyclosporine, and cis-platin. In addition, enhanced urinary ET excretion has been
      found in several forms of renal failure, both acute and chronic, and in diabetes
      mellitus. Thus, urinary ET has the potential of serving as a marker for renal
      disease.

PMID- 8136096
TI  - Effect of withdrawal of antihypertensive drug on depressive mood.
AB  - To evaluate the effects on depressive mood of withdrawal of antihypertensive
      medication, we conducted a randomized, multi-center study with clinical centers
      at the Albert Einstein College of Medicine, Bronx, NY, University of Alabama
      School of Medicine, Birmingham, and the University of Mississippi School of
      Medicine in Jackson. Patients were formerly active participants in the
      Hypertension Detection and Follow-Up Program (HDFP) whose blood pressure was
      controlled with drugs for a period of 5 years. Of 496 patients, 431 had both
      baseline and "1-year" mood scores. Patients, stratified by obesity, were
      randomized to one of three groups: continue the HDFP medication; discontinue
      medication with no dietary intervention, or with sodium restriction and potassium
      increase; or, for those overweight, to a weight reduction intervention.
      Depression was assessed using the CES-D scale (Center for Epidemiological Studies
      -Depressed Mood), administered at baseline and again approximately 1 year after
      randomization. Of the seven treatment groups, only those who continued their HDFP
      medication showed significant improvement in mood from baseline. The overweight
      continue-medication group showed significantly greater improvement compared to
      the no-drugs, no-diet intervention groups, and to the overweight sodium
      restriction group. Patients who had their blood pressure successfully controlled
      with weight reduction had a significant improvement in mood from 11.0 scale
      points to 8.0, P = .006. Comparisons between those withdrawn from diuretic alone
      and those withdrawn from both diuretic plus reserpine were inconclusive. Dietary
      Intervention Study of Hypertension (DISH) shows no evidence that continued use of
      chlorthalidone has a negative impact on quality of life, while our results
      concerning reserpine were inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136097
TI  - Compliance in hypertension: daily v twice daily.

PMID- 8136098
TI  - 1,25-dihydroxyvitamin D as a cardiovascular hormone. Effects on calcium current
      and cytosolic free calcium in vascular smooth muscle cells.
AB  - Clinical and in vitro evidence suggests a role for the calcium regulating
      hormone, 1,25-dihydroxyvitamin D (1,25D) in human and experimental hypertension.
      To establish the cellular basis for this association, we utilized the whole-cell
      version of the patch clamp method and fluorescence spectroscopic techniques to
      measure voltage-dependent calcium channel activity and cytosolic free calcium
      concentrations ([Ca2+]i) in rat tail artery-derived smooth muscle cells, before
      and after the addition of 1,25D. 1,25D significantly increased the calcium
      channel current over the range of test pulses, from -40 to +60 mV, in a dose- and
      time-dependent manner, appearing by 5 to 10 min of exposure, with maximum effects
      by 15 min. At 10 and 30 nmol/L, the current increased to 149 +/- 10% and 221 +/-
      13% of basal activity of 37.75 +/- 7.7 pA and 37.7 +/- 4.5 pA, respectively.
      Similarly, at 10 and 100 nmol/L, 1,25D increased cytosolic free calcium levels
      115 +/- 2% and 171 +/- 11%, from basal values of 99 +/- 32 nmol/L and 116 +/- 10
      nmol/L, respectively. These effects of [Ca2+]i developed slowly over 3 to 4 min.
      Peak values were achieved by 30 min of incubation and were reversible with
      removal of 1,25D from the medium. Altogether, these direct effects of 1,25D on
      calcium current and [Ca2+]i in vascular smooth muscle cells support a role for
      1,25D in vascular physiology, and provide a cellular basis for better
      understanding the involvement of 1,25D in hypertensive vascular disease.

PMID- 8136099
TI  - The Cohen diabetic (non-insulin-dependent) hypertensive rat model. Description of
      the model and pathologic findings.
AB  - The available diabetic hypertensive models are of type I chemically induced
      diabetes in one-clip Goldblatt rat or in the spontaneously hypertensive (SHR)
      rat. We describe here a genetic type II diabetic hypertensive model (CDHM)
      developed by cross breeding the Cohen diabetic rat (CDR) and the SHR. In the
      succeeding generations, sibling pairs with the highest spontaneous blood glucose
      (SBG) and blood pressure (BP) were selected and mated. In the sixth selected
      generation, non-insulin-dependent overt diabetes and hypertension were evident.
      Blood pressure was 171 +/- 1.2 mm Hg, spontaneous blood glucose 340 +/- 22 mg/dL,
      and plasma insulin at 60 min following intragastric (IG) glucose load 83.3 +/-
      10.2 microU/mL. In the CDHM there was severe diffuse diabetic glomerulosclerosis
      and severe hypertensive changes in arteries and arterioles, characterized by
      fibrinoid necrosis and/or "onion skin" lesions, as well as by smooth muscle cell
      hyperplasia. Such vascular changes were not observed in the CDR or in the SHR.
      Myocardial changes were prominent, with foci of ischemic necrosis and
      hyperplastic vascular changes. This model may be useful in probing the mechanisms
      potentiating cardiovascular and renal morbid events in the setting of spontaneous
      hypertension and diabetes.

PMID- 8136100
TI  - Antihypertensive effects of oral calcium supplementation may be mediated through
      the potent vasodilator CGRP.
AB  - Alteration of calcium metabolism and changes in the levels of calcium-regulating
      hormones have been described in essential hypertension. In the majority of the
      reported clinical trials, calcium supplementation has resulted in a decrease in
      blood pressure. However, the mechanisms by which such a response would be
      mediated are entirely unknown. The present study confirmed that daily
      supplementation with 1.4 g of elemental calcium led to a significant decrease in
      both systolic and diastolic blood pressures (P < .01). Decrease in blood pressure
      was negatively correlated with increase in plasma calcitonin gene-related peptide
      (CGRP), measured with radioimmunoassay and by radioreceptor assay (P < .001), and
      positively correlated with decrease in intact parathyroid hormone (PHT) (P <
      .05). Following cessation of calcium supplementation, plasma CGRP levels and the
      blood pressure both reverted back to the base-line values, suggesting a direct
      effect of supplemented calcium on these two parameters.

PMID- 8136101
TI  - Captopril-stimulated renal vein renin measurements in the diagnosis of
      atherosclerotic renovascular hypertension.
AB  - The diagnostic utility of post-captopril renal vein renin (RVR) measurements was
      quantitated in 43 patients (mean age 62, range 41 to 77 years) undergoing
      aortography to rule out renovascular hypertension (RVHT), and then compared with
      that of pre-captopril RVR measurements. Four patterns of post-captopril RVR
      secretion were defined: 1) unilateral hypersecretion (stenotic/peripheral [S/P] >
      2.0) and contralateral suppression (C/P) (< 1.25) (n = 12); 2) bilateral
      hypersecretion (S/P > 2.0, C/P > 1.25) (n = 14); 3) bilateral suppression
      (peripheral plasma renin activity [PRA] < 1.0 ng/mL/h) (n = 12); and 4) "normal"
      (RVR/PRA < 2.0 bilaterally) (n = 5). Using the radiologic findings as the
      definitive test, the sensitivity and specificity of post-captopril RVR
      measurements in detecting unilateral or bilateral renal artery stenoses (85% or
      greater of lumen) was 61 and 96%, and 92 and 90%, respectively, a significant
      improvement compared with those of pre-captopril RVR measurements (44 and 62%,
      and 17 and 93%, respectively). Post-captopril RVR measurements facilitated the
      diagnosis of both hypersecretion and, when present, contralateral suppression of
      renin, and therefore, are useful in the diagnosis of atherosclerotic RVHT, and in
      planning its treatment. However, confirmation by more extensive prospective
      studies, including treatment outcome, is needed.

PMID- 8136102
TI  - Colocalization of 11 beta-hydroxysteroid dehydrogenase and mineralocorticoid
      receptors in cultured vascular smooth muscle cells.
AB  - Colocalization of mineralocorticoid receptors (MR) and 11 beta-hydroxysteroid
      dehydrogenase (11-HSD), the enzyme acting as a protector of MR, in the same cell
      of mineralocorticoid (MC)-responsive tissues is crucial to the concept of enzymic
      regulation of intracellular cortisol levels in these tissues. Such colocalization
      was demonstrated in the epithelial cells of the renal distal tubule. The aim of
      the present study was to examine if MR and 11-HSD activity can be colocalized in
      cells of another target tissue to mineralocorticoids, the arteries. Vascular
      smooth muscle (VSM) cells were cultured, and absence of dedifferentiation was
      ascertained up to the eighth passage. High affinity binding of [3H]aldosterone
      (ALDO) was demonstrated in the intact cultured cells, and Kd and Bmax values were
      calculated from Scatchard plots. The activity of 11-HSD was demonstrated in the
      cultured cells by incubating them with [3H]-cortisol in the presence of
      cofactors, and isolating [3H]-cortisone. Other [3H]-metabolites formed were 11
      beta-hydroxy- and 11-keto-androstenedione. These data support the view that
      arterial tree is a target organ for mineralocorticoids and may be of importance
      in the pathogenetic mechanism of MC-induced hypertension.

PMID- 8136103
TI  - High-fructose diet does not raise 24-hour mean arterial pressure in rats.
AB  - High intakes of the simple sugars--glucose, sucrose, and fructose--have been
      reported to raise significantly systolic pressure in rats. It is not clear,
      however, if under those conditions the acute measurement of blood pressure,
      especially with the tail-cuff technique, represents accurately the effect of the
      diet on mean arterial pressure throughout the day. In this study, 15 Sprague
      Dawley rats (approximately 325 g) were chronically instrumented with arterial and
      venous catheters and placed on a diet containing 61% vegetable starch and 5%
      dextrose; seven rats remained on this diet throughout the study. After 4 days of
      control measurements, eight rats were switched to a diet that substituted 66%
      fructose for the vegetable starch and dextrose. Mean arterial pressure (MAP) was
      measured 20 h/day by computerized methods. MAP during the 4 control days averaged
      100 +/- 3 and 105 +/- 3 mm Hg in low-fructose (LF) and high-fructose (HF) diet
      rats, respectively. Switching to the HF diet caused no change in MAP, and after
      11 days MAP averaged 104 +/- 2 and 108 +/- 3 mm Hg in the LF and HF rats,
      respectively. In addition, the variability of MAP over the 20-h period each day
      was not altered by the HF diet, and raising sodium intake fourfold caused a
      similar rise in MAP in both groups. There also were no significant changes in
      plasma glucose or insulin concentrations. Thus, a change in dietary simple sugar
      content from 5% dextrose to 66% fructose did not change MAP or alter blood
      pressure variability or sodium sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136104
TI  - Localizing value of catecholamine profile in patients with adrenal or ectopic
      pheochromocytoma.

PMID- 8136105
TI  - What is the meaning of racial differences in diurnal blood pressure changes?

PMID- 8136106
TI  - Ethnic differences in the myocardial and vascular reactivity to stress in
      normotensive girls.
AB  - Cardiovascular reactivity to stress has been proposed as a mechanism partially
      responsible for the increased prevalence of essential hypertension in African
      Americans compared with whites. However, few studies have examined ethnic
      differences in cardiovascular reactivity among women. The present study evaluated
      potential ethnic differences in the cardiovascular reactivity to three laboratory
      stressors (postural change, video game challenge, forehead cold stimulation). The
      sample consisted of 171 normotensive girls (74 whites, 97 African-Americans) with
      a mean age of 11.1 +/- 2.7 years, all with positive family histories of essential
      hypertension. African-American girls showed higher resting diastolic blood
      pressures and higher resting total peripheral resistance compared with white
      girls. African-American girls also exhibited higher peak responses in systolic
      and diastolic blood pressure and total peripheral resistance and lower cardiac
      index responses during video game challenge and forehead cold stressor. The
      findings extend previous observations of ethnic differences in blood pressure
      reactivity to stress and indicate that concomitant increases in total peripheral
      resistance appear to account for the greater blood pressure reactivity in African
      American girls.

PMID- 8136107
TI  - Diurnal variations of blood pressure and microalbuminuria in essential
      hypertension.
AB  - Microalbuminuria has been shown in approximately 40% of patients with essential
      hypertension. Previous studies have failed to demonstrate any consistent
      relationship between microalbuminuria and levels of office blood pressure.
      Because average ambulatory blood pressure correlates with incidence of
      cardiovascular morbidity and mortality better than office blood pressure, we have
      studied whether levels of urinary albumin excretion correlate with average
      diurnal, nocturnal, or 24-h blood pressure better than with office blood
      pressure. Sixty-three patients with essential hypertension and 21 healthy
      volunteers were included in the study. Twenty-four hypertensive patients failed
      to show the normal nighttime fall in blood pressure of at least 10/5 mm Hg and
      were defined as "nondippers"; the remaining were defined as "dippers." Office
      blood pressure was not different between dippers and nondippers. However,
      nighttime systolic and diastolic blood pressures were significantly greater in
      nondippers than in dippers. The median urinary albumin excretion in nondippers
      (42 mg/24 h) was significantly greater (P < .001) than in dippers (17.5 mg/24 h),
      and in normal subjects (8.6 mg/24 h). A significant correlation was present
      between nighttime systolic and diastolic blood pressure and urinary albumin
      excretion (UAE) and between 24-h systolic blood pressure and UAE in all
      hypertensive patients; in addition, a significant correlation was present between
      24-h diastolic and nighttime diastolic blood pressure and UAE in nondippers. The
      increased amount of UAE in nondipper hypertensive patients suggests the presence
      of greater renal damage than in dippers.

PMID- 8136108
TI  - Effect of age on the hemodynamic response to posture in nonelderly hypertensive
      patients.
AB  - The objective of this study was to assess the effects of age on the hemodynamic
      response to a change in posture in essential hypertension. Invasive hemodynamic
      measurements were performed in the supine and sitting position in 110 men, aged
      16 to 64 years, in whom cardiovascular complications were virtually excluded. The
      change of systolic and diastolic intraarterial pressure, from 153/83 mm Hg after
      30 min of supine rest to 156 (P < .05)/92 (P < .001) mm Hg after sitting for 10
      min, was not significantly (P > .10) related to age. Heart rate (+9 beats/min)
      and systemic vascular resistance (+4.6 mm Hg/L/min) increased (P < .001) on
      sitting; cardiac output (-1.7 L/min), stroke volume (-31 mL), and pulmonary
      capillary wedge pressure (-2.1 mm Hg) fell (P < .001). Whereas the postural
      changes of heart rate (P < .01), cardiac output (P < .001), stroke volume (P <
      .001), and wedge pressure (P = .06) were less pronounced in older than in younger
      patients, the increase of systemic vascular resistance was not related to age (P
      > .10). The slopes of the postural changes of heart rate and of systemic vascular
      resistance differed significantly (P = .01). The results were not confounded by
      the level of blood pressure or weight. In conclusion, the smaller postural falls
      of cardiac output, stroke volume, and wedge pressure in older patients suggest
      less thoracic blood volume displacement to the lower parts of the body, possibly
      resulting from a lesser peripheral venous distensibility. The increase of heart
      rate in response to the upright posture is less pronounced at older age, whereas
      the reflex control of the peripheral vasculature is preserved and blood pressure
      maintained.

PMID- 8136111
TI  - Treatment with lisinopril normalizes serum concentrations of procollagen type III
      amino-terminal peptide in patients with essential hypertension.
AB  - Procollagen type III amino-terminal peptide (PIIIP) is cleaved off procollagen
      type III during the biosynthesis of type III collagen. Thus, to assess the
      synthesis of collagen type III in essential hypertension, we determined the serum
      concentrations of PIIIP in 24 patients with never-treated essential hypertension
      and in 30 normotensive controls. In addition, serum concentrations of PIIIP were
      measured in 15 patients after receiving lisinopril during 6 months. Serum PIIIP
      was higher in hypertensives than controls (11.20 +/- 0.76 v 8.47 +/- 0.77 ng/mL,
      mean +/- SEM, P < .01). A direct correlation was found between serum PIIIP and
      plasma renin activity (r = 0.54, P < .01) in the group of hypertensives. In
      addition, serum PIIIP was correlated inversely with maximal early transmitral
      flow velocity measured during diastole by Doppler echocardiography (r = -0.74, P
      < .001) in the group of hypertensive patients. The serum PIIIP levels decreased
      significantly in patients treated with lisinopril (11.76 +/- 0.84 v 8.47 +/- 0.66
      ng/mL, P < .01). A significant increase of plasma renin activity and a
      significant decrease of plasma aldosterone was observed in these patients after
      treatment with lisinopril. These results suggest that increased collagen type III
      synthesis is present in patients with essential hypertension. Abnormal synthesis
      of collagen type III in essential hypertension may be related to the activity of
      circulating renin-angiotensin-aldosterone system. Whether an excessive synthesis
      of myocardial collagen type III is responsible for increased serum PIIIP present
      in essential hypertension deserves further investigation.

PMID- 8136110
TI  - Albumin excretion rate and metabolic modifications in patients with essential
      hypertension. Effects of two angiotensin converting enzyme inhibitors.
AB  - A prospective randomized, double-blind, double-dummy study investigated the
      effects of two angiotensin converting enzyme (ACE) inhibitors on urinary albumin
      excretion in nondiabetic patients with mild to moderate essential hypertension.
      At the end of a 4-week placebo run-in period, 36 patients were randomly allocated
      to receive a 12-week course of treatment with quinapril (10, 20, or 40 mg) once
      daily or captopril (25, 50, or 75 mg) twice daily. Seventeen patients in each
      group completed the study. The mean change in mean blood pressure for patients
      taking quinapril (mean dose 32 mg/24 h) was -5 mm Hg (P = .002), and for patients
      taking captopril (mean dose 132 mg/24 h), -9 mm Hg (P = .002). The baseline
      urinary albumin excretion rate in both groups was (mean +/- EEM) 57 +/- 7
      micrograms/min. Fifteen patients in the quinapril group and 12 patients in the
      captopril group had baseline albumin excretion rates of more than 20
      micrograms/min. Mean urinary albumin excretion decreased in patients treated with
      quinapril from 55 to 33 micrograms/min (mean decrease 22 micrograms/min, 95%
      confidence interval [CI], 1 to 43 micrograms/min; P = .031) and with captopril
      from 59 to 41 micrograms/min (mean decrease 18 micrograms/min, 95% CI, 3 to 32
      micrograms/min; P = .025). No significant modifications were observed in serum
      lipid concentrations, serum and urinary electrolytes, and magnesium or phosphorus
      metabolism. Mean urinary calcium excretion decreased in the quinapril-treated
      group (from 219 to 188 mg/24 h; P = .023) but not in the captopril group (from
      264 to 267 mg/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136109
TI  - Calcium antagonists for treatment of diabetes-associated hypertension. Metabolic
      and renal effects of amlodipine.
AB  - In hypertensive diabetics a strict blood pressure control may decrease the
      incidence of cardiovascular and diabetic complications. Long-term experience with
      the use of calcium antagonists is still limited. The metabolic and renal effects
      of long-term (8 months) therapy with amlodipine, 5 to 10 mg daily, were studied
      in 15 hypertensive patients with uncomplicated diabetes mellitus as compared with
      15 patients with essential hypertension. After a 4 week placebo phase, the
      diabetics and essential hypertensive patients did not differ in mean blood
      pressure (156/93 +/- 16/7 v 150/95 +/- 9/5 mm Hg), body weight, creatinine
      clearance, microalbumin excretion, and C-peptide and lipid levels, while serum
      fructosamine was higher in the diabetics. In both groups, amlodipine caused a
      significant and long-lasting decrease of arterial pressure (8%), but did not
      modify creatinine clearance, microalbumin excretion, and serum lipid levels. In
      diabetics indices of diabetic control and the insulin and glucose response to an
      oral glucose tolerance test were unchanged, whereas in essential hypertension the
      insulin response to a glucose load was decreased (P = .033). Amlodipine exerts a
      comparable and long-lasting antihypertensive effect in hypertensive diabetics and
      patients with essential hypertension. Despite the significant decrease in
      arterial pressure, there was no change in urinary microalbumin excretion. Lipid
      metabolism, quality of diabetic control, and the insulin response to a glucose
      load were not affected unfavorably.

PMID- 8136112
TI  - Adrenocorticotrophin-induced hypertension in rats. Role of progesterone and
      digoxin-like substances.
AB  - Adrenocorticotrophin (ACTH) administration raises blood pressure in humans,
      sheep, and the rat. ACTH hypertension can be reproduced in sheep by combined
      infusion of aldosterone, 17 alpha-OH-progesterone, and 17 alpha,20 alpha-OH
      progesterone, and in humans by cortisol. In the rat, ACTH hypertension is
      probably due to corticosterone. Progesterone treatment can prevent ACTH-induced
      hypertension in sheep. This study examined the ability of progesterone to
      antagonize the onset and development of ACTH-induced hypertension in Sprague
      Dawley rats (n = 44). We also investigated the relationship of plasma digoxin
      like substances (DLS) to ACTH hypertension. ACTH (0.5 mg/kg/day) significantly
      increased blood pressure (+24 +/- 5 mm Hg, P < .001) in association with an
      increase of water intake, urine output, and plasma sodium concentration, and a
      decrease of body weight and plasma potassium concentration. ACTH increased plasma
      DLS (+132 +/- 18 pg/mL, P < .01), and there was a positive correlation between
      DLS and blood pressure (r = 0.68, n = 22, P < .001). Progesterone (50 mg/kg/day)
      did not block the development of ACTH-induced hypertension in the rat. Although
      progesterone prevented the ACTH-induced rise in plasma sodium and glucose
      concentration, it did not prevent the decrease in plasma potassium concentration.
      The failure of progesterone to prevent ACTH-induced hypertension in the rat
      argues against a common "hypertensinogenic" mechanism for ACTH hypertension in
      sheep and rat. DLS may play a role in ACTH-induced hypertension in the rat.

PMID- 8136113
TI  - Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells.
AB  - Recently ouabain has been shown to induce transcription of proto-oncogenes in
      different cell types. In the present study, we examined the effect of ouabain on
      the proliferation of cultured vascular smooth muscle cells (VSMCs). Primary
      aortic VSMCs of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and
      the rat VSMC cell line A10, were used. Different concentrations of ouabain (10(
      9) to 10(-5) mol/L) were added to either quiescent or proliferating cells, and
      the cell number, the rate of thymidine incorporation into DNA, and the
      transcription of c-fos and c-myc were examined. The addition of ouabain to
      proliferating VSMC increased the rate of thymidine incorporation into DNA in a
      dose-dependent manner, and induced the transcription of the proto-oncogenes
      within 1 h. This latter response disappeared after 24 h. The number of cells
      significantly increased in response to low concentrations of ouabain (10(-8) to
      10(-7) mol/L), but gradually decreased in response to higher concentrations of
      the agent, probably due to a toxic effect. Addition of ouabain to quiescent
      cells, in medium without serum, did not promote cell growth by any of the
      parameters examined. According to a current theory, endogenous digitalis-like
      substances possess natriuretic and hypertensive properties, and provide the link
      between an excessive intake of salt and high blood pressure. The mitogenic effect
      of ouabain on VSMCs may be a component of this hypertensive action.

PMID- 8136114
TI  - Ethnic differences in circadian hemodynamic profile.
AB  - Since the introduction of 24-h ambulatory blood pressure monitoring (ABPM), some
      studies, although not all, have suggested the presence of a blunted nocturnal
      blood pressure decline in black versus white subjects, a difference that may help
      explain the higher incidence of target organ damage in blacks. To better define
      ethnic differences in diurnal hemodynamic profiles, we studied ABPM recordings
      from 275 black (55.6% women) and 246 white (43.1% women) previously untreated
      subjects, with a similar age distribution (from 20 to 79 years) and a wide range
      of systolic (100-230 mm Hg) and diastolic (50-130 mm Hg) blood pressures. Average
      clinic systolic (diastolic) blood pressures were higher in black v white men by
      10.2 (7.3) mm Hg; P = .04 (P = .004), with a similar trend in women (P = NS). On
      ABPM, blacks had higher average values, a difference that was greater during
      sleep (9.4 mm Hg for systolic blood pressure) than while awake (4.7 mm Hg; P =
      .003). Average diurnal change in systolic blood pressure (awake minus sleep
      values) was 13.1 +/- 0.7 v 18.0 +/- 0.6 mm Hg for blacks v whites (P < .001).
      There was a strong negative correlation between baseline (ie, sleep) blood
      pressure and the diurnal change (r = -0.58; P < .001), but at each given level,
      blacks had a lower daytime increment/nocturnal fall (P = .02). Results for
      diastolic blood pressure and heart rate were similar. The data suggest that the
      smaller diurnal change in blacks may be related in part to their higher blood
      pressure levels, but that there is an additional, independent effect of race.
      This results in a greater 24-h blood pressure load in blacks than whites for each
      given clinic (daytime) value, and may help explain differences in target organ
      damage. Future studies investigating the effects of blood pressure on target
      organs in different populations should consider diurnal profiles in addition to
      clinic blood pressure.

PMID- 8136115
TI  - Exaggerated pressor and chronotropic response to chronic hyperinsulinemia in SH
      versus WKY rats.
AB  - Insulin resistance and the sympathetic nervous system have been suggested to be
      important factors in the blood pressure response to hyperinsulinemia. This study
      was designed to investigate whether the response to chronic hyperinsulinemia in
      14-week-old SH rats (n = 6), which are reported to be insulin resistant and to
      have a hyperresponsive sympathetic nervous system, would differ from that in WKY
      rats (n = 5). Mean arterial pressure (MAP) and heart rate (HR) were monitored 19
      h/day by computer. After a 4-day control period, insulin (1.5 mU/kg/min) and
      glucose (19.3 [WKY] or 13.5 [SH] mg/kg/min) were infused intravenously for 7
      days. Plasma insulin increased from 43 +/- 7 and 68 +/- 7 mU/mL to 75 +/- 4 and
      91 +/- 11 mU/mL in WKY and SH rats, respectively, with no decrease in plasma
      glucose in either group. MAP during control averaged 99 +/- 2 and 130 +/- 4 in
      WKY and SH rats, respectively, and increased 2 +/- 2 mm Hg above control in WKY
      rats and 18 +/- 4 mm Hg in SH rats on day 1 of insulin. However, after day 2 the
      change from control was no longer significantly different between the groups and
      averaged 11 +/- 2 and 15 +/- 6 mm Hg above control on day 7 in the WKY and SH
      rats, respectively. The change in heart rate from control was 5 +/- 5 and 21 +/-
      9 beats per minute in the WKY and SH rats on day 1 of insulin, and this
      difference also diminished with time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136116
TI  - Membrane stretch directly activates large conductance Ca(2+)-activated K+
      channels in mesenteric artery smooth muscle cells.
AB  - Large-conductance, Ca(2+)-activated K+ channels were identified in single smooth
      muscle cells freshly isolated from rabbit superior mesenteric artery. They
      typically showed a reversal potential close to 0 mV in excised, inside-out
      patches in symmetric 130 mmol/L [K+] with a unitary conductance of 260 pS, and
      increased activity at more positive potentials and/or when [Ca2+] was raised at
      the cytosolic surface of the membrane. Both in cell-attached and in excised,
      inside-out configurations, stretching the membrane patch by applying suction to
      the back of the patch pipette increased the activity of these channels without
      changing either the unitary conductance or the voltage sensitivity of the
      channel. Stretch activation was repeatedly seen in inside-out patches when both
      surfaces were bathed with a 0 Ca2+ solution containing 2 or 5 mmol/L EGTA to
      chelate trace amounts of Ca2+, making it highly improbable that stretch
      activation could be secondary to a stretch-induced flux of Ca2+. Consequently,
      stretch activation of large-conductance, Ca(2+)-activated K+ channels in
      mesenteric artery smooth muscle cells seems to be due to a direct effect of
      stretch on the channel itself or on some closely associated, membrane-bound
      entity.

PMID- 8136117
TI  - Quantification of Ca(2+)-ATPase in erythrocytes from subjects with essential
      hypertension or Raynaud's phenomenon.
AB  - The increased peripheral vascular resistance in subjects with essential
      hypertension and in subjects with primary Raynaud's phenomenon is thought to be
      the consequence of an impaired control of intracellular Ca2+ in vascular smooth
      muscle cells. Abnormal membrane handling of Ca2+ in human essential hypertension
      is not limited to vascular smooth muscle cells but has been demonstrated in a
      number of blood cells, for example, erythrocytes. Ca(2+)-ATPase activity and
      Ca(2+)-ATPase densities were measured in erythrocyte membranes from healthy
      volunteers and subjects with essential hypertension or with Raynaud's phenomenon.
      We found no significant differences between the three groups in the Ca(2+)-ATPase
      activity and in the number of Ca(2+)-ATPase immunoreactive sites per erythrocyte.
      Furthermore, we could not demonstrate any influence of sex or age on these two
      parameters. We conclude that, in essential hypertension and in Raynaud's
      phenomenon, the Ca2+ extrusion capacity of the erythrocytes is not altered.

PMID- 8136118
TI  - Low external K+ regulates Na,K-ATPase alpha 1 and beta 1 gene expression in rat
      cardiac myocytes.
AB  - Incubation of mammalian cells in medium containing low K+ is often associated
      with an increase in Na,K-ATPase activity and content. In the present studies, we
      investigated the effect of low K+ on the regulation of Na,K-ATPase alpha 1 and
      beta 1 gene expression in primary cultures of neonatal rat cardiac myocytes.
      Northern blot hybridization analysis indicated that exposure of cardiocytes to a
      medium containing 0.3 mmol/L K+ for 72 h resulted in 1.8- and 3.3-fold increases
      in the abundance of alpha 1 and beta 1 mRNAs, respectively, compared with control
      cells exposed to 5.4 mmol/L K+. To investigate the molecular mechanism of the low
      K effect on beta 1 mRNA content, we constructed chimeric genes with a full-length
      and deleted portion of the 5' end of the rat beta 1 gene linked to the firefly
      luciferase gene. Transient transfection experiments using these constructs
      indicated that beta 1 gene sequences between -102 and +151 base pairs (bp) are
      required for low K(+)-induced trans-activation of reporter gene expression. Taken
      together, these results indicate that low K+ induction of beta 1 mRNA abundance
      in neonatal rat cardiac myocytes is mediated by regulatory DNA sequences in close
      proximity to the site of transcription initiation of the beta 1 gene.

PMID- 8136119
TI  - The influence of applying magnesium preparation on the content of chosen ions of
      human plasma.
AB  - We have analyzed the influence of the administration of the "Calcimag"
      preparation, containing Mg+2 and Ca+2 ions, on the content of chosen blood plasma
      ions: Mg+2, Na+, K+, CI-, Ca+2 and phosphorus subject to the age of the
      volunteers. The preparation was administrated three times a day one tablet. The
      tendency to the decrease of magnesium concentration in plasma has been noticed
      subject to the age of the individuals. The administration of magnesium-calcium
      preparation caused statistically significant increase of magnesium in plasma for
      persons with hypomagnesemia and slight but characteristic increase for those with
      normomagnesemia.

PMID- 8136120
TI  - Introduction of magnetic beads in diagnosis: a simple and rapid method to detect
      mutations of beta globin gene, directly amplified from blood.
AB  - In this communication we present the results obtained by the use of magnetic
      beads in diagnosis, for the identification of genetic variants at the molecular
      level by sequencing, in comparison with the more laborious method of the
      production of ssDNA with asymmetric PCR. We compared the two techniques studying
      variants of beta globin gene: Hb Abruzzo [beta 143 (H21) His -> Arg] and Hb D Los
      Angeles [beta 121 (GH4) Glu -> Gln].

PMID- 8136121
TI  - [Recombinant DNA technology in the development of new antibiotics].

PMID- 8136122
TI  - Differentially labeled mutant oligonucleotides for analysis of protein-DNA
      interactions.
AB  - We have developed a method to produce a set of four duplex oligonucleotides, each
      with a different labeled base at a given position, from one template-primer
      combination. The template oligonucleotide is synthesized with a mixture of all
      four bases at the position of interest, and the primer oligonucleotide hybridizes
      to the template at all bases 3' from the position of interest. Specifically
      labeled substrates are then produced by differential incorporation of each of the
      four labeled nucleotides in four separate reactions. This method is more cost
      effective than synthesizing four separate duplex oligonucleotides with different
      base pairs at the position of interest. We have successfully used this method to
      test nucleotide substitutions at several positions of a DNA recognition site for
      the phage T4 type II DNA topoisomerase.

PMID- 8136123
TI  - Enhanced ethidium fluorescence of large DNA electrophoresed in gels submersed in
      an immiscible solvent.
AB  - Agarose gel electrophoretic separation of a lambda/HindIII DNA marker containing
      detectable fragments of 23 to 2 kb was carried out in the conventional submarine
      apparatus and in the horizontal gel slab apparatus of Wieme, using identical
      samples, agarose, gel width and procedure for ethidium bromide staining. In the
      Wieme apparatus, the gel on its microscope slide support is immersed in an
      immiscible solvent such as petroleum ether or silicone oil. Although band
      resolution and speed of migration are equivalent between gels run in the two
      systems, the relative fluorescence intensity of the ethidium bromide-stained
      bands is substantially more responsive to an increase in DNA length in the Wieme
      gels than in the submarine gels. The predicted relative fluorescence is by an
      average factor of 0.5 less than that observed after electrophoresis in the Wieme
      apparatus but is by an average factor of 3.4 more than that observed on bands
      derived from the submarine technique.

PMID- 8136124
TI  - Competitor template RNA for detection and quantitation of hepatitis A virus by
      PCR.
AB  - PCR was used to introduce a 63-bp deletion into the putative RNA replicase coding
      sequence of hepatitis A virus. RNA was synthesized in vitro from the deletion
      mutant cloned into a transcription vector. Upon amplification by PCR, cDNA made
      from the competitor RNA generated an amplified fragment that could be easily
      distinguished from the product generated from wild-type hepatitis A virus genomic
      RNA by gel electrophoresis, when the same primers were used, without further
      manipulation. The competitor RNA was used as a positive control in PCR-based
      detection of very low copy numbers of hepatitis A virus genomic RNA in the
      presence of unrelated hard-shell clam RNA. When the competitor RNA was used for
      competitive PCR to quantitate wild-type RNA, the presence of one template at a 10
      fold to 100-fold higher level almost completely inhibited product formation from
      the underrepresented template. The competitor RNA should be useful as a control
      for reverse transcription and PCRs to determine hepatitis A virus genome RNA when
      accidental contamination of test samples by a wild-type positive control template
      would compromise the results.

PMID- 8136125
TI  - A biological method for examining the effect of codon changes in a conserved
      region of DNA polymerase.
AB  - The vaccinia virus genome encodes a DNA polymerase that is similar to other DNA
      polymerases. A mutation in the polymerase gene at a site that is adjacent to
      conserved residues allows viral replication in the presence of aphidicolin. Since
      wild-type virus is converted to aphidicolin-resistance by site-directed
      mutagenesis, it was feasible that active virus with substituted conserved
      residues could be detected by linking alterations to the aphidicolin-resistance
      mutation. Altered DNA, from a PCR, was introduced into virus by a marker transfer
      procedure. DNA from plaques of drug-resistant virus was amplified, and the
      product was sequenced to check for the conserved residue alteration. An
      alteration that introduced a Bg1I site was designed to facilitate the selection
      of drug-resistant virus containing substituted residues. One positive result was
      the replacement of two amino acids, tyrosine and alanine, by tryptophan and
      threonine. The failure to substitute aspartic acid for tyrosine indicates that
      drastic changes of the conserved sequence are not tolerated. Although the
      limitations associated with negative results apply, the method provides an in
      vivo assay for selecting a polymerase with conserved residue changes.

PMID- 8136126
TI  - Analysis of duplex DNA by triple helix formation: application to detection of a
      p53 microdeletion.
AB  - Conventional methods for mutation detection include Southern hybridization,
      direct sequencing of PCR products and single-strand conformation polymorphism
      analysis. We present an additional screening method that employs oligonucleotide
      directed DNA triple helix formation to detect mutations within homopurine
      sequences. The proposed strategy is simple and may be of particular value when
      screening many DNA samples for changes involving particular homopurine sites. We
      have applied the method to the analysis of a clinically relevant 8-bp micro
      deletion in the human p53 tumor suppressor gene. Affinities of oligonucleotide
      probes toward radiolabeled wild-type and mutant p53 DNA duplexes were quantitated
      by electrophoretic mobility shift assays. Recombinant plasmids carrying wild-type
      or microdeleted forms of the p53 homopurine sites of interest were created.
      Dimethyl sulfate footprinting was used to verify intended probe specificities.
      Duplex PCR products amplified from plasmid constructs were directly probed by
      incubation with labeled oligonucleotides. After electrophoresis and
      autoradiography, patterns of triple helix formation allowed discrimination
      between the mutant and wild-type p53 sequences. Direct DNA analysis by triple
      helix formation may simplify other procedures that normally require DNA
      denaturation and hybridization.

PMID- 8136127
TI  - New lambda and plasmid vectors for expression cloning in mammalian cells.
AB  - This report describes the construction of a new family of lambda phage and
      plasmid cloning vectors. lambda GDST3/T7 allows cDNA insertion up to 14 kb; it is
      derived from lambda NM1151 by the insertion of a multiple cloning site containing
      eight unique restriction sites. The two asymmetrical SfiI sites are flanked by
      the T3 and T7 promoters for direct sequencing and in vitro
      transcription/translation. The same multiple cloning site is also present in both
      orientations in the eukaryotic expression plasmids, pGDSV3 and pGDSV7. By
      exploiting the superior discrimination of the signal-to-noise ratio of the lambda
      vectors for primary screening (by either nucleic acids or antibody probes),
      relevant cDNAs can thus be efficiently transferred through SfiI sites into the
      plasmids pGDSV3/7 for functional secondary screening by expression in mammalian
      cells.

PMID- 8136128
TI  - Stable, continuous large-scale production of human monoclonal HIV-1 antibody
      using a computer-controlled pilot plant.
AB  - A completely automated pilot plant used for fermentation has been employed with
      direct digital control (DDC) technology for monitoring and regulating growth of
      human cells. A human hybridoma cell line (3D6) producing anti-human
      immunodeficiency virus (HIV)-1 antibodies was used as a model for large-scale
      production (300-liter airlift fermentor) in continuous culture. Parameters
      controlled were pH, dissolved oxygen, temperature and the flow rate of four gases
      used in the process. A control strategy was implemented to achieve constant fluid
      velocity and mixing by maintaining the rate of gas flow at a constant level.
      Another advantage of this approach was that the total gas flow required for
      optimal fluid circulation was reduced from 1 volume gas/volume fermenter/hour
      (vvh) to 0.3 vvh. Use of a low flow rate eliminated the serious problems of
      foaming, which contributed significantly to cell destruction, shorter filter-life
      and other considerations. Dilution rate was optimized at laboratory scale for
      maximum productivity, which results in relatively low viability. At a dilution
      rate of 0.0076 h-1, a total cell density of 6-7 x 10(5) cells/ml with a viability
      of approximately 75% was maintained during long-term continuous cultivation.
      These growth conditions resulted in a product titer stabilized in the range of 35
      micrograms IgG/ml. Batchwise purification was achieved with a recovery of more
      than 50% and a final purification of active monoclonal antibody representing
      about 99% product. Results from isoelectric focusing and Western blotting
      demonstrated batch-to-batch consistency of the purified human monoclonal antibody
      to HIV-1 during the continuous growth process.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136129
TI  - An improved general method to generate internal standards for competitive PCR.

PMID- 8136130
TI  - A rapid, PCR-based assay for episomal replication.

PMID- 8136131
TI  - PCR amplification using deoxyinosine to replace an entire codon and at ambiguous
      positions.

PMID- 8136132
TI  - A functional assay for Taq DNA polymerase in PCR.

PMID- 8136133
TI  - Cloning of PCR products can be inhibited by Taq polymerase carryover.

PMID- 8136134
TI  - Proteolytic digestion of genomic samples followed by chelation inactivation prior
      to PCR amplification.

PMID- 8136135
TI  - AmpliGrease: "hot start" PCR using petroleum jelly.

PMID- 8136136
TI  - SASA: a simplified, reliable method for allele-specific amplification of
      polymorphic sites.

PMID- 8136137
TI  - A method to insert a DNA fragment into a double-stranded plasmid.

PMID- 8136138
TI  - A simplified method for the preparation of fungal genomic DNA for PCR and RAPD
      analysis.

PMID- 8136139
TI  - High G + C-content DNA markers for pulsed-field gel electrophoresis.

PMID- 8136140
TI  - Inhibition of RNA polymerases by digoxigenin-labeled UTP.

PMID- 8136141
TI  - Improved downward capillary transfer for blotting of DNA and RNA.

PMID- 8136142
TI  - Efficient removal of hybridization signal from RNA dot blots probed with
      digoxigenin-labeled cRNA.

PMID- 8136143
TI  - Hybridization of DNA in dried gels provides increased sensitivity compared with
      hybridization to blots.

PMID- 8136144
TI  - Cholesterol-specific probe for lipoproteins immobilized on nitrocellulose
      membranes.

PMID- 8136145
TI  - Enhancement effect of storage buffer on regeneration of immunosorbent surfaces.

PMID- 8136146
TI  - A procedure for RT-PCR amplification of mRNAs on histological specimens.
AB  - Detection in combination with localization of low copy gene expression can be
      difficult to achieve. The use of reverse transcription PCR on tissue sections
      with a fluorescent marker provides localization of mRNA expression on a cellular
      level, and when combined with confocal microscopy and image analysis it also
      allows for an estimate of the relative intensity of fluorescence. A good example
      of the application of this method is the localization of nerve growth factor
      (NGF) mRNA expression in the inner ear. NGF through indirect tests appears to be
      present in this system, yet NGF mRNA could not be localized with in situ
      hybridization using radiolabeled riboprobes. Using fluorescent in situ RT-PCR, we
      can easily detect the presence of NGF mRNA and localize it to specific cell types
      within the maturing inner ear.

PMID- 8136147
TI  - Gender determination by multiplex PCR amplification of alphoid repeat sequences
      from single cells.
AB  - Alphoid repeat sequences on the X and Y chromosomes were successfully and
      consistently coamplified to determine the sex of single cells. Buccal cells
      served as a convenient model for single blastomeres obtained from preimplantation
      embryos through in vitro fertilization. The potential use of this technique for
      preimplantation genetic diagnosis is discussed.

PMID- 8136148
TI  - A distinctive property of Tth DNA polymerase: enzymatic amplification in the
      presence of phenol.
AB  - The ability of thermostable DNA polymerases to mediate template-dependent DNA
      synthesis in the presence of phenol has been examined as monitored by
      amplification of a specific Borrelia burgdorferi rRNA sequence. Tth DNA
      polymerase displayed the unique property of maintaining both DNA- and RNA
      dependent DNA polymerase activities in the presence of 2%-5% (vol/vol) of phenol
      saturated PBS buffer. Tth DNA polymerase mediated reverse transcriptase activity
      was unaffected by phenol-saturated phosphate-buffered saline concentrations as
      high as 15% (vol/vol). By contrast, Taq DNA Polymerase was inactive under these
      conditions. The ability to function in the presence of phenol can greatly
      simplify reverse transcriptase, PCR and reverse transcription-PCR protocols since
      the phenol-saturated aqueous phase of a phenol partition can be added directly to
      the reaction mixtures. The simplicity of the procedures described should have
      applicability to a broad range of basic research, clinical and forensic
      applications.

PMID- 8136149
TI  - An end-trimming method to amplify adjacent cDNA fragments by PCR.
AB  - We describe a method for cDNA cloning by PCR, which we named "an end-trimming
      method." This method can be used for PCR amplification and cloning of unknown
      cDNA fragments adjacent to a short stretch of a known sequence by using a
      combination of a sequence-matched primer with an ATCG sequence added to the 5'
      end (5'-ATCG-primer) and an adaptor-(dT)17-primer (dT-primer). The fragments
      amplified by PCR using a 5'-ATCG-primer, which were modified to have a 5'-ATC
      overhang by blocking the G site, were exclusively cloned into pUC19 with the
      vector having a 3'-TAG-5' complementary overhang with a confined direction of
      inserted fragments. Practical application of this method for the determination of
      rat amidophosphoribosyltransferase cDNA resulted in successful cloning of
      adjacent cDNA fragments.

PMID- 8136150
TI  - A rapid and efficient, nonradioactive method for screening recombinant DNA
      libraries.
AB  - In this report we present a rapid and inexpensive PCR-based method to screen
      recombinant DNA libraries. The efficiency of this method was demonstrated by the
      isolation of clones of interest from three different libraries using different
      vector systems. This method is nonradioactive and makes it easier to handle a
      large number of samples since there is no need for DNA extraction. The advantages
      and applications of the method are discussed.

PMID- 8136151
TI  - A Mn(2+)-enhanced, RGD-dependent adhesion technique for isolation of adult rat
      type II alveolar epithelial cells for immediate functional studies.
AB  - This report describes a Mn(2+)-enhanced, RGD-dependent adhesion technique for
      isolation of adult rat type II cells for immediate functional studies. Lung cells
      were dissociated by 30 U/ml porcine pancreatic elastase and 50 micrograms/ml
      trypsin instilled in the airways. Macrophages were selectively removed by
      adhesion on purified normal goat IgG-coated petri dishes. Type II cells were
      isolated by adhesion for 45 min, on ProNectin-F-coated dishes in the presence of
      0.5 mM Mn2+. The adherent type II cells were then detached with 0.025% trypsin, 2
      mM EDTA in Hepes-buffered saline, pH 7.4. The technique yielded 1.5 to 1.7 x
      10(7) (n = 8) cells from a 150- to 200-g rat. Greater than 90% of the cells were
      pure type II cells as judged by tannic acid staining and immunostaining with
      monoclonal antibody 4AmAb, which recognizes pneumocin, a type II cell marker. The
      technique reduced the time required for cell isolation from the current 16 to 24
      h to 2 to 2.5 h, using commonly available laboratory equipment and reagents.
      Cells isolated by the procedure were used to study cell adhesion and spreading on
      purified extracellular matrix components in the presence of different divalent
      cations. Mn2+, Co2+, Ni2+, and Mg2+ enhanced adhesion of freshly isolated type II
      cells to fibronectin and ProNectin-F, while Ca2+ did not promote type II cell
      adhesion on these substrata. RGDS peptide at 1 mg/ml concentration inhibited the
      divalent cation-enhanced cell adhesion.

PMID- 8136152
TI  - Effect of extracellular ATP and UTP on fluid transport by human nasal epithelial
      cells in culture.
AB  - We have investigated the effect of both adenosine triphosphate (ATP) and uridine
      triphosphate (UTP) on the fluid transport, transepithelial electric potential
      difference (PD), and unidirectional chloride flux when applied apically to
      cultured human surface respiratory epithelial (HSRE) cells in a double
      compartment chamber. The effects of ATP and UTP (both 100 microM) were examined
      in cells either untreated or pretreated with 100 microM amiloride in lactated
      Ringer's solution. ATP or UTP was added to the apical solution in a 100
      microliters final volume. After a 2-h incubation period, the change in fluid
      transport was measured by weighing the apical fluid. Compared with control,
      amiloride blocked the fluid absorption by HSRE cells. The addition of ATP or UTP,
      either alone or after pretreatment with amiloride, induced a similar and
      significant increase in the apical fluid and chloride flux (P < 0.001 and P <
      0.005, respectively). The changes in both fluid transport and chloride flux were
      accompanied by changes in PD. A blocker for chloride transport, 4,4'
      diisothiocyano-2,2'-stilbene disulfonate, at 500 microM significantly blocked the
      ATP-stimulated fluid transport (P < 0.05) and chloride flux (P < 0.01). These
      results support the hypothesis that extracellular ATP and UTP increase the fluid
      transport by respiratory epithelial cells and may be useful in the hydration of
      mucus and respiratory mucosa.

PMID- 8136153
TI  - Intraperitoneal in vivo gene therapy to deliver alpha 1-antitrypsin to the
      systemic circulation.
AB  - The utility of replication-deficient recombinant adenovirus vector-mediated
      transfer and expression of the alpha 1-antitrypsin (alpha 1AT) cDNA to peritoneal
      mesothelial tissues was evaluated as a means of delivering alpha 1AT to the
      systemic circulation. Preliminary studies with Ad.RSV beta gal, an adenovirus
      vector expressing the Escherichia coli lacZ gene (beta-galactosidase), showed
      that intraperitoneal injection of 10(9) plaque-forming units (pfu) to cotton rats
      resulted in beta-galactosidase activity in mesothelial cells lining the
      peritoneal cavity. After intraperitoneal administration of 10(9) pfu of Ad alpha
      1AT (an adenovirus vector containing the human alpha 1AT cDNA), human alpha 1AT
      was detectable in serum for up to 24 days, with a maximal level of 3.4
      micrograms/ml at 4 days. Expression of the exogenous gene was localized to the
      peritoneal mesothelium as PCR analyses detected no evidence of expression of the
      exogenous gene in any other tissues evaluated. Anti-adenovirus vector antibodies
      were detectable in serum after intraperitoneal administration of the recombinant
      vectors, including antibodies with neutralizing activity. Repeat administrations
      of adenovirus vectors to the peritoneal cavity at 1 wk and 1 mo after the initial
      dose failed to show gene expression, but repeat administration 3 mo after
      demonstrated measurable gene transfer and expression. Together these observations
      suggest replication-deficient adenovirus-mediated gene transfer to the peritoneal
      mesothelium offers a promising means to transfer alpha 1AT to the systemic
      circulation, although immunity induced against the adenovirus may limit frequent
      repetitive dosing.

PMID- 8136154
TI  - Effect of furosemide on prostaglandin synthesis by human nasal and bronchial
      epithelial cells in culture.
AB  - Inhaled furosemide protects asthmatic subjects against bronchial obstruction
      caused by indirect provocants. We have attempted to correlate the protective
      effect of furosemide with its ability to alter prostaglandin (PG) synthesis by
      the airway epithelium. Human epithelial cells from nasal polyps and bronchi were
      cultured in DME-Ham's F12 medium with 10% fetal calf serum. Confluent cells (days
      6 through 8) were incubated for 30 min in fresh medium, and the PGs in the
      supernatant were measured by radioimmunoassay. Spontaneous output (ng.ml-1.mg-1
      cell protein) was as follows (mean +/- SEM): PGE2 = 7.74 +/- 2.10 (n = 12), PGF2
      alpha = 1.66 +/- 0.12 (n = 15), 6-keto-PGF1 alpha = 4.32 +/- 1.37 (n = 11), PGD2
      = 0.73 +/- 0.16 (n = 11) for bronchial cells and PGE2 = 7.24 +/- 0.80 (n = 32),
      PGF2 alpha = 1.38 +/- 0.12 (n = 17), 6-keto-PGF1 alpha = 6.79 +/- 2.50 (n = 15),
      PGD2 = 0.42 +/- 0.07 (n = 17) for nasal cells. Incubation with arachidonic acid
      (25 micrograms/ml) for 30 min significantly increased the amounts of the four
      PGs. Incubation with furosemide (10(-4) M) for 30 min caused a marked reduction
      in both basal and arachidonic acid-stimulated production of PGE2 and PGF2 alpha
      but did not reduce production of 6-keto-PGF1 alpha and PGD2. Incubation with
      bumetanide (10(-4) M) for 30 min did not modify the PGE2 synthesis by nasal
      epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136155
TI  - Characterization of exosurf (surfactant)-mediated suppression of stimulated human
      alveolar macrophage cytokine responses.
AB  - Previous studies in our laboratory demonstrated that the synthetic surfactant
      Exosurf (Burroughs Wellcome Co.) inhibited endotoxin-stimulated cytokine
      secretion from human alveolar macrophages in vitro. The purpose of the present
      study was to further characterize the suppressive effects of Exosurf, which
      consists of dipalmitoylphosphatidylcholine (DPPC), cetyl alcohol (spreading
      agent), and tyloxapol (nonionic dispersing agent). Suppression was not stimulus
      specific in that Exosurf also significantly reduced cytokine production elicited
      by either Staphylococcus aureus or recombinant interleukin-1. Suppression was
      also mediated by a modified bovine surfactant (Survanta), which, in contrast to
      Exosurf, contains the surfactant-associated proteins B and C, and several
      different phospholipids, but no cetyl alcohol or tyloxapol. This suggests that
      suppression of macrophage cytokines is not specific to Exosurf. Both cell
      associated and secreted tumor necrosis factor and interleukin-1 were reduced by
      Exosurf, indicating that Exosurf is not simply blocking cytokine release. At 3 h,
      cytokine mRNA levels were not different between Exosurf-treated and untreated
      cells. However, at 8 and 24 h, cytokine mRNA levels were lower in Exosurf-treated
      cells. The observations that mRNA levels were decreased at 8 and 24 h and that
      cellular cytokine release was not blocked suggest that Exosurf's effect may in
      part be pretranslationally mediated. Collectively, these data add to previous
      work indicating that pulmonary surfactant may play a critical role in reducing
      inflammatory cytokine production associated with the adult respiratory distress
      syndrome and similar disorders.

PMID- 8136156
TI  - Surfactant protein A labeling kinetics in newborn and adult rabbits.
AB  - Surfactant protein A (SP-A), the major hydrophilic protein specifically
      associated with surfactant, has multiple metabolic and host defense functions as
      well as primary surfactant biophysical functions in association with the other
      surfactant proteins and lipids. To characterize its kinetics of secretion and
      clearance from the airspace, we measured specific activity-time curves for
      alveolar and lamellar body associated SP-A following the intravascular and/or
      intratracheal administration of the radiolabeled precursors Tran 35S-label
      containing primarily methionine and cysteine or [3H]methionine to newborn and
      adult rabbits. Alveolar SP-A specific activity peaked 30 min after precursor
      injection in both newborn and adult rabbits, and labeled SP-A was not detected in
      lamellar bodies until after 2 h. In newborns, a second peak of labeled SP-A
      appeared at 15 h. In both newborns and adult rabbits, lamellar body specific
      activity-time curves were most consistent with SP-A entering lamellar bodies via
      a recycling pathway from the airspaces. The airspace clearance of SP-A in adult
      rabbits had a biologic half-life of about 4.5 h. There was very little decrease
      in SP-A specific activity in the newborn rabbits, indicating minimal catabolism.
      These studies demonstrate secretion of endogenously synthesized SP-A by a pathway
      separate from lamellar bodies. The kinetics of secretion of SP-A and the
      surfactant phospholipid in newborn and adult rabbits indicate separate metabolic
      pathways.

PMID- 8136157
TI  - Modulation of surfactant protein D expression by glucocorticoids in fetal rat
      lung.
AB  - The production of pulmonary surfactant protein D (SP-D) increases abruptly during
      late gestation, and the accumulation of this protein in lung tissue is increased
      following the exposure of fetal rats to glucocorticoids in utero. To examine the
      regulation of these events, we administered dexamethasone (Dex; 1 mg/kg/day
      intramuscularly for 3 days), or saline, to timed-pregnant rats and harvested the
      lungs on days 19 to 21 of gestation. Samples of pooled fetal lungs were analyzed
      for SP-D protein, mRNA, and gene transcription by immunoblot, Northern
      hybridization, and nuclear run-off transcription assays. Lungs from 19 day
      controls showed barely detectable levels of SP-D gene transcription and
      negligible accumulation of SP-D message. However, SP-D transcription and the
      accumulation of SP-D mRNA and protein were readily detected in lungs from 19 day
      Dex-treated rats. Dexamethasone also caused dose- and time-dependent increases in
      SP-D protein and mRNA accumulation in 19 day fetal lung explants.
      Immunohistochemistry of control 19 day lung using antibodies to rat SP-D showed
      only weak labeling of a small number of airway epithelial cells. By contrast, Dex
      exposed rats showed strong staining of columnar and cuboidal epithelial cells
      lining airways and epithelial tubules and cuboidal cells lining primitive air
      sacs. In situ hybridization assays showed similar alterations in the number,
      intensity, and distribution of labeled epithelial cells in 19 day Dex-exposed
      lungs and demonstrated labeling of alveolar type II and nonciliated columnar
      cells in adult lung. These data indicate that the accelerated lung maturation
      accompanying glucocorticoid exposure in utero is associated with a precocious
      increase in SP-D gene transcription and protein production by pulmonary
      epithelial cells.

PMID- 8136158
TI  - Lectin-mediated interactions of surfactant protein D with alveolar macrophages.
AB  - Surfactant protein D (SP-D) is a calcium-dependent carbohydrate-binding protein
      that is secreted into the pulmonary airspaces by type II epithelial and Clara
      cells. Previous studies have shown that SP-D can bind to specific surfactant
      phospholipids and to glycoconjugates associated with the surface of various
      microorganisms, consistent with possible roles in surfactant metabolism and
      pulmonary host defense. We now describe specific saccharide-mediated interactions
      of SP-D with alveolar macrophages in lung tissue and in vitro. Biotinylated rat
      SP-D showed specific binding to alveolar macrophages in sections of rat lung;
      this labeling was inhibited by competing saccharides or EDTA. In addition, the
      binding of 125I-SP-D to isolated alveolar macrophages in the presence of calcium
      was time-dependent, saturable, and reversible and was preferentially inhibited by
      known monosaccharide and disaccharide ligands for SP-D. Scatchard analysis gave
      an apparent single class of binding sites with a Kd = 1.4 x 10(-6) M. We
      speculate that the multivalent structure of SP-D mediates bridging interactions
      between microbial glycoconjugates or surfactant phospholipids and specific
      glycosylated ligands expressed on the surface of phagocytic cells.

PMID- 8136159
TI  - Cell cycle-dependent expression of cyclin D1 and a 45 kD protein in human A549
      lung carcinoma cells.
AB  - Cyclin D1, which is suggested to have a role in G1 control during the cell cycle,
      is genetically linked to BCL-1 and is widely overexpressed in parathyroid,
      breast, and squamous cancer cells. We postulated that cyclin D1 regulation may
      also be important in lung cancer. Therefore, we characterized the cell cycle
      dependent expression of cyclin D1 at both mRNA and protein levels in synchronized
      human A549 lung carcinoma cells. Monospecific anti-cyclin D1 C-terminal peptide
      antibodies recognized both p36cyclinD1 and an as-yet uncharacterized 45 kD
      protein (p45). A549 cells were synchronized with well-studied drugs. Cyclin D1
      mRNA expression remained relatively constant, with less than a twofold
      fluctuation during the cell cycle and with a minor peak at M phase. However, the
      p36cyclinD1 protein fluctuated during the A549 cell cycle and was expressed at
      very low levels in late G1 and at the G1/S boundary, but then increased in S
      phase and peaked at M phase. In contrast, p45 protein was expressed at relatively
      high levels in late G1 and reached maximal levels at the G1/S boundary, was
      expressed at decreased levels in S phase, and then had disappeared by M phase.
      Moreover, p45 was highly expressed only in transformed alveolar epithelial cells,
      but not in normal rat alveolar epithelial cells or fetal rat lung fibroblasts in
      primary cultures. In mink Mv1Lu cells, the expression of p45 was totally blocked
      by transforming growth factor-beta 1 treatment or contact inhibition. p45 protein
      was phosphorylated on serine, threonine, and tyrosine residues in A549 cells in
      culture. The phosphorylation of the p45 protein was cell cycle-regulated and
      reached its maximal levels at G2/M phase. The p45 protein had a different peptide
      map from p36cyclinD1 after cleavage with N-chlorosuccinimide. Immunoprecipitation
      studies showed that p45 was also anti-ubiquitin immunoreactive during the cell
      cycle. We conclude that p36cyclinD1 and the p45 protein are differentially
      regulated in a cell cycle-dependent manner in A549 cells. Although p45 is
      antigenically related to p36cyclinD1, it is probably not a closely cyclin-related
      protein. We speculate that p45 may be associated with malignant transformation
      and may play a distinct role from p36cyclinD1 in regulation of the cell cycle in
      A549 cells.

PMID- 8136160
TI  - Adenovirus E1A 13S gene product up-regulates the cytomegalovirus major immediate
      early promoter.
AB  - Latent cytomegalovirus (CMV) infection is often reactivated in the lung. We
      postulated that this reactivation could occur by stimulation of the CMV major
      immediate early (IE) promoter by other viruses that infect the lung. The specific
      aim of this study was to investigate whether adenovirus early proteins could
      stimulate the CMV IE promoter in inflammatory cells. We transfected the
      monocyte/macrophage THP-1 cell line and the T-lymphocyte Jurkat cell line with
      plasmids coding for adenovirus E1A 12S or 13S proteins, along with a plasmid
      containing the CMV IE promoter region linked to the chloramphenicol
      acetyltransferase (CAT) reporter gene. In unstimulated THP-1 cells, the E1A 13S
      gene product increased CMV IE CAT activity by 18-fold compared with cells
      containing the control E1A plasmid. This effect was not seen in cells transfected
      with the E1A 12S plasmid. There was a similar effect of the E1A 13S gene product
      in LPS-stimulated THP-1 cells. In unstimulated Jurkat cells, the E1A 13S gene
      product stimulated CMV IE CAT activity by 19-fold compared with cells containing
      the E1A control plasmid; the E1A 12S gene product had no effect. There was a
      similar effect of the 13S E1A gene product in phorbol myristate acetate
      stimulated Jurkat cells. These findings demonstrate that the CMV IE promoter can
      be stimulated by early viral proteins of adenovirus in inflammatory cells. These
      observations could be important for understanding the reactivation of latent CMV
      infection.

PMID- 8136161
TI  - Expression of heat shock proteins in human lung and lung cancers.
AB  - Heat shock proteins (HSP) are highly conserved molecules whose expression is
      induced in eukaryotic cells following a broad spectrum of environmental stresses.
      These proteins can also be expressed by virally transformed cells and cancer
      cells and are important targets for T lymphocytes. Little is known about the
      abundance and distribution of HSP in the normal lung, the effect of cigarette
      smoking on their expression, or their expression in human lung carcinomas. We
      have used monoclonal antibodies coupled with immunohistochemical and
      immunoelectrophoretic techniques to evaluate the distribution of four different
      HSP (HSP 90 kD, HSP 73 kD/constitutive, HSP 72 kD/inducible, and HSP 63 kD) in
      normal lung (n = 14) and lung cancers (n = 15). In lung tissue from nonsmokers (n
      = 7), bronchiolar epithelial cells were intensely positive for HSP 90 kD and HSP
      72 kD/inducible and weakly reactive for HSP 63 kD. Most macrophages also
      expressed these HSP at low levels, but no other parenchymal or
      immune/inflammatory cells were positive. Cigarette smoking did not modify the
      distribution or the intensity of HSP in bronchiolar epithelial cells, and
      macrophages from smokers expressed similar or lower levels of these HSP. Tumor
      cells from 14 of 15 lung carcinomas expressed one or more of the HSP.
      Considerable heterogeneity in the expression of HSP by cells in a given tumor was
      observed, explained in part by differences in the differentiation of the cells.
      Detection of HSP by immunohistochemical and immunoelectrophoretic techniques gave
      similar results for HSP 72 kD/inducible and HSP 90 kD.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8136162
TI  - Predicting the unpredictable.

PMID- 8136163
TI  - The St. Jude medical prosthesis in the mitral position.
AB  - To study the long-term results of the St. Jude medical prosthesis in the mitral
      position, 520 patients were evaluated who had undergone mitral valve replacement
      with St. Jude medical (SJM) prosthesis. Eighteen patients or 3.5% died in the
      early postoperative period (within 30 days after operation). The total follow-up
      was 2872 patient-years and late deaths occurred in 23 cases. Postoperative
      cerebral embolism occurred in six, bleeding complication in five, and thrombosed
      valve in two patients. Postoperative anti-coagulant therapy was initiated with
      both dipyridamole (300 mg/day) and warfarin potassium. After discharge from our
      hospital the patients underwent routine examination of their thrombo-tests or
      prothrombin times at least every 2-3 months, and the major thromboembolic or
      bleeding complication rate was 0.45%/100 patient-years. In a period of 12 years,
      severe hemolysis following implantation was seen in seven patients. The cause of
      this hemolysis was perivalvular leakage in two patients but there were no
      leakages in the other five patients, although preoperative moderate to severe
      liver dysfunction was noted. Ninety-three percent of the patients were followed
      up, and their postoperative New York Heart Association functional classes were I
      or II in 88.6% of the cases. Their clinical results after mitral valve
      replacement with SJM prosthesis in the anti-anatomical position showed excellent
      durability and a low incidence of valve-related complications.

PMID- 8136164
TI  - Active infective endocarditis: surgical approach.
AB  - From January 1982 to December 1991, 65 interventions were performed in 61
      patients with active infective endocarditis (IE): 32 on native valves (Group 1)
      and 33 on prosthetic valves (Group 2). In Group 1, 23 patients had a known
      previous valve disease; major preoperative clinical complications occurred in 16
      patients (50%); 84% were in NYHA classes III and IV. In Group 2 major
      preoperative clinical complications occurred in 13 patients (44.8%); 86% were in
      NYHA classes III and IV. The mean time interval between the onset of hemodynamic
      impairment of varying degrees and surgery was 13 +/- 15 days for Group 1, and 8
      +/- 11 days for Group 2. In all cases, the native valves or prostheses were
      replaced by mechanical valve prostheses. Particular procedures were performed in
      three patients in Group 1 and five patients in Group 2. In Group 1 there were 8
      hospital deaths (25%) and 11 (34.4%) non-fatal complications. In Group 2 there
      were 9 deaths (31%) and 14 (48.3%) non-fatal complications. Risk factors for
      hospital death were "preoperative low cardiac output syndrome" and "time interval
      between the onset of cardiac failure and surgery" in Group 1, "cardiac
      failure+sepsis" in Group 2, "time interval between the onset of cardiac failure
      and surgery" and "particular procedures" in all 61 patients. Sepsis alone and the
      type of pathogenic agent does not significantly affect the risk of death. The
      recurrence of acute IE was 12.6% in Group 1, and 20% in Group 2. The incidence of
      reintervention was 12.6% in Group 1 and 35% in Group 2.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8136165
TI  - Post-operative blood loss following cardio-pulmonary bypass in children.
AB  - Significant post-operative bleeding may occur following cardio-pulmonary bypass,
      sometimes necessitating early re-exploration. Two questions were asked by this
      study. Firstly, in children undergoing cardio-pulmonary bypass, can pre
      operative, operative and immediately post-operative variables be used to predict
      post-operative blood loss? Secondly, in the same patient group, can the same
      variables be used to predict the surgical intervention of re-exploration for
      excessive bleeding within 12 h of surgery? In a prospective study of patients
      operated on in a 9-month period, bleeding fell rapidly in the first 3 h after
      surgery and early re-exploration for bleeding was necessary in 8 of the 206
      patients. The only significant predictor of post-operative blood loss was minimum
      oesophageal temperature, low values being associated with greater blood loss
      (correlation r = -0.19 (P < 0.05)). With regard to re-exploration for bleeding, a
      long bypass time (P < 0.05) and abnormal pre-operative coagulation indices (P <
      0.01) were significant and independent predictors. The data were also used to
      create a practical nomogram relating re-exploration for bleeding to hourly post
      operative blood loss.

PMID- 8136166
TI  - Acute traumatic rupture of the thoracic aorta: immediate or delayed surgical
      repair?
AB  - The appropriate management of traumatic aortic rupture is often difficult to
      determine, particularly if the rupture is associated with severe additional
      lesions. Between 1986 and 1991, ten consecutive patients with acute traumatic
      rupture of the thoracic aorta (ATRTA) and concomitant injuries were initially
      treated medically and submitted to delayed aortic repair. Within the same period
      no other patient had emergency reconstruction of the thoracic aorta. Diagnosis of
      ATRTA was established immediately after admission in eight patients. Five
      patients underwent emergency surgery for severe concomitant injuries. With regard
      to the aortic lesion, all patients were managed medically and submitted to
      pharmacological treatment in an attempt to reduce cardiac shear forces. None of
      the patients developed clinical signs of imminent free rupture while waiting for
      aortic surgery. In the absence of a significant hemothorax and when no
      coarctation syndrome is evident, the risk of free aortic rupture is considered to
      be rather low if the patient reaches the hospital in a stable circulatory
      condition. Postponement of aortic reconstruction is particularly indicated when
      severe concomitant lesions preclude safe immediate repair of the aortic tear.
      Following the patient's recovery from associated major injury, aortic surgery can
      be performed as a low risk procedure using cardiopulmonary bypass which is
      recognised as the most effective technique to prevent spinal cord ischemia and to
      reduce the risk of paraplegia.

PMID- 8136167
TI  - Thoracoscopic use of laser in intractable pneumothorax.
AB  - A neodymium:yttrium, aluminum, garnet (Nd:YAG) laser was used via the
      instrumentation port of a standard thoracoscope for the sealing of air leaks,
      ablation of bullae, transection of adhesions and partial parietal pleurectomy in
      13 patients with intractable pneumothorax. The mean duration of tube thoracostomy
      prior to treatment was 10 days (range 4 to 21 days). All patients had intractable
      air leakage. Three patients had chronic lung collapse of over 50% despite
      adequate chest drainage. All cases were treated with thoracoscopic laser. The
      source of air leakage was found to be ruptured bullae in 11 cases and a lung tear
      in 2 cases. In five cases the bullae were multiple. In 11 cases the air leakage
      stopped within 24 h of treatment, with a single self-limiting episode of
      recurrent air leakage. In two of the cases of chronic pneumothorax the lung
      failed to expand because of sizable bronchopleural fistulae. They required
      thoracotomy stapling of bullae and limited thoracoplasty. The mean duration of
      tube thoracostomy after thoracoscopic laser in the 11 successfully treated
      patients was 2.72 days (range 1 to 5 days). We conclude laser-assisted
      thoracoscopy is a useful therapeutic option when treating persistent air leakage.
      In most cases this method prevents prolonged periods of tube thoracostomy and
      obviates thoracotomy. In cases of chronic collapse of the lung with
      bronchopleural fistulae this technique may not be successful.

PMID- 8136168
TI  - Value of computed tomography and mediastinoscopy in preoperative evaluation of
      mediastinal nodes in non-small cell lung cancer. A study of 569 patients.
AB  - The efficacy of computed tomography (CT) and mediastinoscopy as staging
      modalities to assess mediastinal lymph node status was evaluated in 569 patients
      with a presumed resectable non-small cell lung cancer (NSCLC). Computed
      tomography scan was performed in every patient and followed by mediastinoscopy in
      331 and by thoracotomy in 477 patients. Mediastinal lymph nodes on CT larger than
      1.5 cm were considered pathological. Overall, CT had a sensitivity of 69%, a
      specificity of 71% and an accuracy of 71% in identifying mediastinal lymph node
      metastases. For mediastinoscopy these figures were 72%, 100% and 89%,
      respectively. Computed tomography accuracy was distinctly lower in squamous cell
      carcinomas and in central tumors, as CT sensitivity was significantly lower in
      left-sided tumors. The positive predictive value (PPV) of CT in T1 lesions (29%)
      and PPV and negative predictive value (NPV) of CT in T2 squamous cell carcinomas
      (30% and 83%, respectively) were low, so questioning its use in those instances.
      We perform a mediastinoscopy in every situation except for squamous cell
      carcinomas or small (less than 3 cm) peripheral tumors in the absence of enlarged
      mediastinal lymph nodes. This selective attitude is rewarding since a) the number
      of pN2 in the straight thoracotomy group was only 16% versus 41% in the
      mediastinoscopy group, b) the exploratory thoracotomy rate in the straight
      thoracotomy group was low (4.6%).

PMID- 8136169
TI  - The use of bovine internal mammary artery (Bioflow) grafts in coronary artery
      surgery.
AB  - Over a 3-year period 17 patients underwent a total of 25 coronary artery bypass
      grafts utilising bovine internal mammary artery [BIOFLOW]. Three patients died in
      the peri-operative or early post-operative period allowing detailed information
      to be gathered on 14 patients. Seven patients who had had a total of 11 Bioflow
      grafts implanted underwent post-operative coronary angiography at a mean time of
      19 months after surgery revealing occlusion in all the Bioflow grafts. Two
      patients who underwent aortic valve replacement combined with single Bioflow
      grafts were symptom-free and refused re-study. Two patients who had three
      coronary grafts each, including single Bioflow grafts, refused re-study though
      one of them had recurrent anginal symptoms. Two patients, one with recurrent
      anginal symptoms, who had a total of four Bioflow grafts were considered unfit
      for restudy on medical (non-cardiac) grounds. One patient with two Bioflow grafts
      and recurrent symptoms refused long-term follow-up. Despite reports of good early
      patency rates with the Bioflow graft, we have not found this to be the case even
      when patients were anticoagulated post-operatively. We do not recommend the use
      of this graft as early occlusion is to be expected, which may result in an early
      return of anginal symptoms.

PMID- 8136170
TI  - Sternal wound dehiscence after internal mammary artery harvesting. Logical
      management.
AB  - There is clear evidence that the internal mammary artery is superior to other
      forms of vascular conduit in surgical coronary revascularisation. Its patency
      rate at 10 years is of the order of 2-3 times that of autologous saphenous vein.
      Unfortunately, harvesting of the internal mammary is associated with an increased
      incidence of sternal wound complications, probably due to temporary sternal
      devascularisation. The restoration of sternal blood supply has been shown to
      occur after several weeks. It is proposed by this group that delayed primary
      closure of dehisced wounds after 3-4 weeks is an effective way of dealing with
      this malignant and, fortunately, rare complication of arterial coronary artery
      revascularisation.

PMID- 8136171
TI  - Severe superior vena caval syndrome after the Mustard repair in a patient with
      persistent left superior vena cava.
AB  - This report describes our experience with a 6-year-old girl with dextro
      transposition of the great arteries and persistent left superior vena cava, who
      manifested severe superior vena caval syndrome following a Mustard repair. A
      direct end-to-end anastomosis of the left superior vena cava to the left atrial
      appendage, which formed part of the systemic venous atrium, was performed with
      excellent relief of the obstruction. The rationale for application of this method
      is discussed as an alternative to the use of cardiopulmonary bypass for intra
      atrial baffle revision.

PMID- 8136172
TI  - A solitary metastasis in the heart from Ewing's sarcoma.
AB  - We present a patient with a solitary metastasis in the heart 8 years after
      treatment for Ewing's sarcoma. Exploratory thoracotomy was performed and biopsies
      were taken. Despite high dose ifosfamide, the patient died a few weeks after
      surgery.

PMID- 8136173
TI  - "Mold-like" calcification of the left atrium and of the pulmonary veins. Total
      endoatriectomy in a patient undergoing mitral valve replacement.
AB  - Mold-like left atrial calcification is a rare aspect of rheumatic mitral valvular
      disease. Its interest lies in the difficulty of surgical technique during
      interventions for valvular substitution. This is a case report in which the total
      excision of the calcified mold by a wide endoatriectomy was necessary in order to
      substitute the stenotic mitral valve.

PMID- 8136174
TI  - Using "unsuitable" hearts for transplantation.
AB  - Donor availability is the single most limiting factor in heart transplantation.
      From a consecutive series of 100 heart donors, there were 21 which fell well
      outside our minimum criteria on initial inspection: mean arterial pressure (MAP)
      more than 60 mm Hg, central venous pressure (CVP) less than 12 mm Hg, pulmonary
      capillary wedge pressure (PCWP) less than 12 mm Hg, left ventricular stroke work
      index (LVSWI) more than 15 g.m. on inotropes less than 5 mcg/kg per min. Of these
      13 out of 21 had a MAP less than 55 mm Hg, 6 out of 21 a CVP more than 15 mm Hg
      and 2 out of 21 were on inotropes at more than 20 mcg/kg per min. Following full
      invasive monitoring another 14 donors fell outside our criteria; 5 had a mean
      LVSWI of 12.4 g.m. and 9 had a mean PCWP of 19.6 mm Hg. Following the institution
      of our hormone-based pharmacological resuscitation regime 30 of these donors
      yielded 19 transplantable hearts and 11 transplantable heart-lung blocks. The
      other five were not used due to left ventricular hypertrophy (2), inotrope
      dependency (2) and persistent poor function (1). Twenty-five of the 30 recipients
      of these organs (83.3%) are alive and well, 4-25 months post transplant. Four
      early deaths occurred; one arrhythmia (heart), one acute respiratory distress
      syndrome (heart), one cerebrovascular accident (heart lung) and one infection
      (heart, lung and liver). One death occurred at 90 days from tamponade (heart).
      Aggressive and focussed donor management has helped us to maintain our levels of
      transplant activity, without compromising the outcome--a 30-day mortality of
      16.2% in 1989, 11.8% in 1990 and 6.8% in 1991.

PMID- 8136175
TI  - mu-Chain gene expression in common variable immunodeficiency.
AB  - Three patients with common variable immunodeficiency (CVID) were analyzed for
      translation from mu mRNA by the cell-free translation method and for expression
      of mu mRNA by northern blotting. In cases 1 and 2, the mu chain was not detected
      in the products by cell-free translation nor was mu mRNA detected by northern
      blotting. In case 3, mu mRNA was detected at a low level. This suggests that the
      disorders occur between rearrangement of the Ig genes and transcription of the C
      mu gene in cases 1 and 2, and that the functions of rearrangement and
      transcription are qualitatively preserved to a certain degree in case 3. Thus,
      the pathogeneses of CVID are variable and more research on regulatory mechanisms
      of B cell development is necessary to understand each case of CVID.

PMID- 8136176
TI  - Genetic, structural, and functional studies of a C3-like protein in the marsupial
      Setonix brachyurus.
AB  - A monospecific goat antiserum was prepared against a putative C3 protein (QuC3)
      from serum of the Western Australian macropod Setonix brachyurus (quokka) using
      the classical method previously used to produce antiserum against C3 from other
      mammalian species. Sodium dodecyl sulphate-polyacrylamide gel electrophoretic
      analysis of reduced immunoprecipitated QuC3 revealed two polypeptide chains with
      an estimated M(r) of 128,000 and 82,000, respectively--presumably reflecting
      subunit molecules similar to the C3 alpha and beta subunits found in other
      mammalian species. No variation in the size of either of the QuC3 alpha or beta
      subunits was found in different quokka serum samples. Furthermore, no variation
      in the electrophoretic mobility of QuC3 was detected amongst the same samples
      using a standard immunofixation electrophoretic technique. The addition of
      zymosan or immune complexes to fresh quokka serum resulted in activation of QuC3.
      Immune complex mediated activation of QuC3 was inhibited by the addition of EDTA
      and Mg(2+)-EGTA. By contrast, EDTA only inhibited activation of QuC3 following
      incubation of fresh quokka serum with zymosan, suggesting that the quokka has a
      classical and an alternative C3 activation pathway, similar to those found in
      eutherian mammals. This study has shown for the first time that one of the
      macropod marsupials (S. brachyurus) has a C3-like protein with similar structural
      and functional characteristics to C3 found in eutherian mammals. However, unlike
      C3 in other mammalian species, genetic variability of the structure of the quokka
      C3-like protein may be restricted.

PMID- 8136177
TI  - In situ localization of HLA class I mRNA in human testis.
AB  - We have used a 0.35-kilobase (kb) antisense RNA probe complementary to the
      monomorphic regions of both classical and nonclassical HLA class I sequences to
      detect histocompatibility-class-I-antigen-specific mRNA in human testicular
      tissue. The message has been clearly detected in the interstitium while less
      intensive staining was revealed in the peribasal compartment of the seminiferous
      epithelium.

PMID- 8136178
TI  - T cells and their role in allergies.
AB  - The molecular and cellular mechanisms which up-regulate IgE synthesis in most
      atopic patients are only incompletely understood. There is no doubt that T cells
      play a prominent role in the B cell immunoglobulin switch to IgE. T-cell-derived
      interleukin (IL)-4 is a specific inducer of IgE synthesis which activates B cells
      to proliferate and, furthermore, induces other cells to release cytokines which
      enhance IgE synthesis. Additional costimulatory signals are required, however,
      for B cell activation and the consequent immunoglobulin switch to IgE. Besides
      physical B/T cell interaction, direct B cell activation through anti-CD40
      provides such a signal. IL-4-induced B cell activation is amplified by other
      cytokines such as IL-5, IL-6, IL-3, probably IL-9, and tumor necrosis factor
      alpha, whereas interferon (IFN)-gamma, IFN-alpha, transforming growth factor-beta
      and IL-12 are able to inhibit IL-4-induced IgE synthesis. These different IgE
      synthesis-modulating lymphokines are secreted by different T cell subsets, TH1
      and TH2. While IgE synthesis is activated by TH2-derived lymphokines, TH1 cell
      clones exhibit cytolytic activity. The detection of allergen-specific T cells in
      peripheral blood mononuclear cells (PBMNCs) of atopic patients, with a lymphokine
      profile similar to TH2, and the predominance of TH2 cells in PBMNCs of these
      patients might be one explanation for increased serum IgE concentrations in
      atopic individuals. It is not known, however, which stimulus leads to a
      predominant expression of TH2 cells over TH1 cells in atopic patients with
      consequently increased IgE synthesis.

PMID- 8136179
TI  - Murine hybridomas secreting monoclonal antibodies reacting with Mlsa antigens.
AB  - Murine monoclonal antibodies have been developed from spleens of AKR mice
      hyperimmunised with the monoclonal antibody against TCR-V beta 6. Two new
      monoclonal antibodies called AL-12-3 and AL-32-7 were able to specifically block
      Mlsa-induced but not MHC-induced mixed lymphocyte responses in a dose-dependent
      manner. Both antibodies are mouse IgG3 lambda chain isotype and bind to Mlsa
      bearing lymphocytes from different strains of mice. The availability of such
      antibodies may well facilitate future research aimed at immunochemical and
      molecular characterization of Mls determinants.

PMID- 8136180
TI  - [On terminology and classification of mental retardation].

PMID- 8136181
TI  - [Pathogenesis of hypoxic encephalopathy during pre- and peri-natal periods].
AB  - Hypoxic encephalopathy during the late gestation and perinatal period occupies a
      large part as a cause of mentally and physically handicaps. An extensive study on
      the pathogenesis and pathophysiology of the hypoxic brain damage is, therefore,
      the matter of urgency to minimize the occurrence of handicapped children. The
      main factors and/or processes relating to hypoxic or hypoxic-ischemic brain
      damage are (1) structural and functional immaturity of the brain vascular system
      and (2) a metabolic cascade triggered by hypoxia. As the following metabolic
      cascade subsequent to hypoxia has been partly made clear; (a) disturbance of the
      energy metabolism, (b) excessive release of excitatory amino acids and subsequent
      activation of NMDA and K/Q receptors at the cell membrane, (c) collapse of the
      membrane ion pump, and (d) increase in turnover of membrane phospholipids.

PMID- 8136182
TI  - [Energy metabolism and neural activity in hippocampal slices of developing rat
      brain].
AB  - Hippocampal slices were prepared from 4-day, 7-day and 10-day-old, and adult rat
      brains. Energy use rate and oxygen consumption rate were determined in each
      slice. Neural activity (population spikes, PS) was recorded in the CA1 pyramidal
      cell layer and correlated with ATP and creatine-P levels during deprivation of
      oxygen and/or glucose. The energy use rate of respective slices was 1.09-P
      mmol/gDNA/min in 4-day-old, 2.93 in 7-day-old, 3.42 in 10-day-old and 4.75 in
      adult rat, respectively. The oxygen consumption rate for slices from 4-, 7-, and
      10-day-old and adult rats was 0.13, 0.24, 0.47 and 0.8-O2 mmol/gDNA/min,
      respectively. Thus energy use rate as well as oxygen consumption rate increased
      during development and the difference in the time course of the increase between
      energy use and oxygen consumption indicated clearly that the energy production in
      the immature brain is mainly supported by anaerobic glycolysis whereas in mature
      rat by aerobic metabolism. The correlation between neural function (amplitude of
      PS) and the level of ATP of each slice during oxygen and/or glucose indicated
      that the presence of glucose is essential for the preservation of the neural
      activity in addition to the maintenance of ATP levels in the slice.

PMID- 8136183
TI  - [Pathophysiology of fetal distress].
AB  - Pathophysiology of fetal distress has not been elucidated completely so far. But
      there has been a rapid progress in the studies both in vitro and in vivo which
      investigated the causes of neuronal death by hypoxia. At the initiation of
      hypoxemia, elevation of fetal blood pressure will occur due to constriction of
      fetal peripheral vessels, and this results in fetal heart rate slowing and
      respiratory compromise. During moderate hypoxemia, circulating blood is
      redistributed to the brain, heart and adrenals at the expense of peripheral
      organs (lung, skin, etc). During prolonged hypoxemia, blood flow to the brain
      stem is maintained and even greater than that in other brain regions. Neuronal
      activity of brain stem, an autonomic center, is important for survival of a
      fetus. As hypoxia progresses, glucose in metabolized anaerobically, lactate
      concentration elevates, and concentrations of high-energy phosphates decrease in
      the cerebrum. When cerebral metabolism has collapsed finally, neuronal membranes
      depolarize, voltage-gated Ca+2 channels open and Ca+2 flux into the cytoplasm
      increases. These changes result in neuronal death. It is considered that
      glutamates, oxygen radicals and other substances are involved in the increase of
      Ca+2 influx. These studies suggest that hypoxic stimulation should be avoided in
      the chronically deteriorating fetus for prevention of unrecognized fetal brain
      damage.

PMID- 8136184
TI  - [Involvement of excitatory amino acids in the brain damage of neonatal asphyxia].
AB  - Besides their role as neurotransmitters, excitatory amino acids (EAAs) in the
      developing brain are crucially involved in plasticity and excitotoxicity which
      are modified by their distinct ontogeny. Postsynaptic EAA system activities,
      particularly of the N-methyl-D-aspartate and quisqualate receptors, are
      transiently enhanced early in life. This transient enhancement is presumably
      beneficial to the immature brain because physiologic activation of the EAA system
      plays a critical role in plasticity of early learning and morphogenesis. At the
      same time, this transient hypersensitivity renders the immature brain vulnerable
      to pathologic excitation of the EAA system (excitotoxicity) as observed during
      neonatal hypoxia-ischemia.

PMID- 8136185
TI  - [Cerebral ischemia and neuronal death].
AB  - The neurons in the hippocampus, striatum, and cerebral or cerebellar cortex are
      particularly vulnerable to a short period of ischemia. Following brief ischemic
      insult, neurons die after a latent period for a few days (delayed neuronal
      death). To account for this selective vulnerability to ischemia, glutamate
      calcium hypothesis has come to be widely accepted. Glutamate, a major excitatory
      neurotransmitter, increases during ischemia. The hypothesis proposes that
      accumulated extracellular glutamate in turn triggers an increase of intracellular
      Ca2+ and eventually neuronal cell death. When neurons are subjected to sublethal
      ischemia, they express stress response and become transiently tolerant to further
      ischemia. These characteristics of ischemic neuronal death following brief
      ischemia indicate that neuronal death under such situation is not due to simple
      destruction of the cell. On the contrary, the fate of neurons following ischemia
      seems to depend on the basic cellular function which determines death or
      survival. This assumption is partially supported by the fact that some
      neurotrophic factors can save neurons following ischemic. However, the further
      basic mechanism of ischemic neuronal cell death is still unknown.

PMID- 8136186
TI  - [Hypoxic brain damage and higher cortical dysfunction in children].
AB  - 1) Twenty-one children with right hemiplegia and 17 with left hemiplegia were
      studied as to emotional differences using the Toddler Temperament Test. Right
      hemiplegic children were less adaptable than controls or left hemiplegic, while
      left hemiplegic children were found to be more approachable than controls or
      right hemiplegic ones. These emotional features were similar to those of adult
      hemiplegics. We speculate that these characteristics emotions are associated with
      the damage to each hemisphere. 2) Eighteen patients with spastic diplegia (SD)
      after preterm birth were studied to clarify the relationship between visuo
      perceptual impairment (VPI) and their cerebral lesions. The VPI was significantly
      correlated with the volume of peritrigonal white matter. In another psychological
      study, SD with preterm birth also showed impairment of stereoscopic vision. We
      suggest that the VPI might be caused by the impairment of stereoscopic vision.

PMID- 8136187
TI  - [Pathogenesis of hypoxic encephalopathy during pre- and peri-natal periods:
      conclusion].
AB  - Perinatal asphyxia is a well recognized cause of cerebral palsy and related
      disabilities. However, uncertainties exist regarding the degree of asphyxia
      required to cause brain injury. Determination of degree of asphyxia is a simple
      matter of measuring blood gases and pH. However, the mechanism of asphyxia
      required to produce cellular damage in a particular individual varies widely,
      depending not only on depth and duration of the asphyxia but even more on other
      biochemical changes, especially glucose, excitatory amino acids, calcium
      activated protein, or the receptor side of ionic channels. The mechanism of
      delayed neuronal cell death or cell-to-cell connection is also mysterious. The
      immature brain is not a reduced version of the adult brain. Studies should
      develop to a wide variety of approaches to clear the complex interactions between
      birth asphyxia and anoxic brain damage.

PMID- 8136188
TI  - [Habilitation for handicapped children, mainly for children with visual and
      hearing impairment, speech-language disorder, and hyperkinetic disorder].
AB  - This symposium was focused on habilitation for children with visual and hearing
      impairment, speech-language disorder, and hyperkinetic disorder. New and variable
      approaches were reported in topics of habilitation for these handicapped children
      by an ophthalmologist, an otorhinolaryngologist, a child neurologist, a speech
      therapist and an educational psychologist. Many points of these approaches were
      then discussed.

PMID- 8136189
TI  - [Care of visual impairment in children and adolescents].
AB  - Visual impairment refers to a loss of visual acuity or one or more functions of
      the eye and visual system. It is not necessarily a disability or a handicap for
      the individual. The majority of visually impaired children are multihandicapped.
      Diagnostic and treatment centers have been introduced in an attempt to resolve
      present difficulties in providing health care to the multihandicapped.
      Pseudoretardation can occur in blind children if adequate opportunities are not
      provided for learning. Early diagnosis of visual impairment is important for
      obvious medical reasons. Early referral of blind children and their families to
      agencies for help is crucial. Almost invariably, mothers are the first to suspect
      that something is wrong with their infants' eyes. An ophthalmological
      examination, rather than simple reassurance, is needed. How an ophthalmologist
      leads parents through the period after diagnosis and the following next few weeks
      will affect the child's life much more than is generally realized. There is a
      need for a multidisciplinary team approach to evaluation and treatment of blind
      children. Cerebral palsy and profound visual impairment are a bad combination.
      Visual impairment alone does not predispose to a specific learning disability.
      Partially sighted students can be helped in various ways to function in their
      class.

PMID- 8136190
TI  - [Therapeutic education for young hearing-impaired children].
AB  - Modern therapeutic education of young hearing-impaired children is premised on
      the active use of residual hearing for helping the deaf child learn language and
      speech. In this case, measurement of degree of the child's hearing loss and
      proper fitting of hearing aids are indispensable. Today, accurate measurement of
      hearing can be made even in infancy by the combined use of behavioral audiometry
      and auditory brain stem response audiometry. Fitting hearing aids for young
      hearing-impaired children is possible, if there is an experienced clinician.
      During the period 1973-1991, I conducted a home training program to 1,613 young
      hearing-impaired children at the Department of Otolaryngology, Teikyo University
      Hospital. Out of the 1,613 children, 222 were under one year old, 481 one year
      old, 470 two years old, 246 three years old, 104 four years old, 69 five years
      old and 21 six years old. In 1983, we made a follow-up study of hearing-impaired
      children who had received my home training program and were receiving compulsory
      education at that time. According to the replies of 87 children to our
      questionnaire, approximately 70 per cent of the children were attending ordinary
      schools.

PMID- 8136191
TI  - [Total care of children with speech disorders].
AB  - The health care of children with speech disorders, ranging from diagnosis to
      handling by local health centers, was reported based on our experience in Fukui
      Prefecture. With regard to diagnosis, it was stressed that both medical
      diagnostic and developmental diagnostic viewpoints are necessary. With respect to
      practical aspects of health care, the role of physicians in a treatment team and
      the formation of a team in response to the specific type of disorder was
      discussed. In addition, various problems and their handling within the context of
      the social environment surrounding the care of children with speech disorders was
      also covered. Lastly, it should be stressed that fundamentally the therapy of
      speech disorders should not rely solely on personal training; an understanding of
      the mind of children affected by speech disorders is vital to successful
      treatment.

PMID- 8136192
TI  - [The role of speech therapists on speech language disordered children].
AB  - As psychological and physiological development and circumstances vary
      considerably, the problems of speech and language in children are further
      complicated. The speech therapists (ST) who have been concerned with these
      children and their families are requested eagerly to reconsider and control their
      own communicative attitude. Furthermore, STs have to improve clinical technique
      that is appropriate to each child. In this report, the author shows the outline
      of the speech and language problems of children, and discusses the merit and
      demerit of speech therapy itself. The clinical approach for motor speech
      disturbance and sensory language disorder is also described.

PMID- 8136193
TI  - [Diagnosis and drug treatment in hyperactive children].
AB  - A critical review was given to the diagnostic transition of hyperactive children,
      i.e., from attention deficit disorder to attention deficit-hyperactivity
      disorder, in the American Psychiatric Association's Diagnostic and Statistical
      Manual of Mental Disorders. Based on the new diagnostic criteria for hyperactive
      children, or hyperkinetic disorders in ICD-10, 12 of 122 (9.8%) children with a
      birthweight less than 1,500 grams have found to show hyperkinetic disorders
      during ordinary follow-up examinations at 4 to 6 years of age. Discontinuation of
      stimulants during school holidays, or the "drug holidays" procedure, was
      recommended not only because a child's response to stimulants could be
      reconfirmed but also because the side effect of growth retardation could be
      avoided. Three typical drug responders with hyperactivity were presented. Case 1
      was a 19-year-old male with some autistic features and tics. He had been taking
      pemoline from 10 to 13 years of age, but showed no side effects. Case 2 was a 15
      year-old boy with epileptic EEG abnormalities, and had been also taking pemoline
      from 6 to 10. He was attacked by a partial seizure with secondary generalization
      just 2 months after the drug administration. Recurrence of epileptic seizures was
      prevented by additional medication of an anticonvalsant , carbamazepine. Case 3
      was a 13-year-old boy with enuresis nocturna and with several febrile seizures,
      and had been taking clomipramine, a tricyclic antidepressant, from 4 to 6. The
      antidepressant proved very effective to his hyperactivity and temper tantrum, but
      not to his enuresis.

PMID- 8136194
TI  - [Psycho-educational approach for hyperactive children].
AB  - There are two significant psychoeducational methods as therapeutic approach for
      hyperactive children. The one, a method of assessing hyperactivity, is the
      behavioral modification technique. The other, which is further contrary to the
      first, is a neuropsychological procedure. We investigated the following
      behavioral features in terms of the second method, such as equilibrium abilities,
      tactile defensiveness and vestibular-proprioceptive processing. Concerning the
      psycho-educational therapy for hyperactive children with developmental
      disabilities, it is very important to promote the improvement of such
      potentialities as integrative abilities by means of multisensory stimulation.
      Then, it will needed further to plan the treatments that modulate the functional
      relationship between sensory input and behavioral output. The focus of these
      treatments is put on improving the neural organization and promoting the adaptive
      behavior of hyperactive children.

PMID- 8136195
TI  - [Brain death in infancy and childhood].

PMID- 8136196
TI  - [Physiology of dreaming].

PMID- 8136197
TI  - [Temperature effect on ischemic brain injury].
AB  - The effect of manipulating the brain temperature during cerebral ischemia was
      investigated in Wistar rats subjected to 30 min 4-vessel occlusion. Three brain
      temperature profiles were compared: 1. Spontaneous decrease in brain temperature
      during ischemia from 36 to 31 degrees C (spontaneous hypothermia; n = 5); 2.
      Constant brain temperature of 30 degrees C induced by selective head cooling
      (induced hypothermia; n = 5); and 3. Constant brain temperature of 36 degrees C
      induced by selective heating of the head (normothermia; n = 5). The core
      temperature was maintained constant at 37 degrees C in all groups. In the
      spontaneously hypothermic brains, 16% of the CA1 neurons survived after 30 min
      ischemia. Induced hypothermia significantly increased this percentage to 69%, but
      maintenance of the brain temperature at normothermia decreased neuronal survival
      to 1%. Normothermia of the brain also led to morphological injury outside the
      vulnerable regions, greater variability of the morphologic lesions, an increase
      in mortality, a marked loss of body weight, and prolongation of EEG suppression,
      as compared to in both hypothermic groups. These findings clearly demonstrate
      that maintaining the brain temperature at normothermia by selective heating of
      the head aggravates ischemic injury and, in consequence, should not be used to
      investigate the effectiveness of protective drugs for brain ischemia.

PMID- 8136198
TI  - [Role of arachidonic acid metabolites on development of ischemic cerebral edema
      in rat middle cerebral artery occlusion].
AB  - The products resulting from arachidonic acid metabolism of the both cyclo
      oxygenase and lipoxygenase pathways possess strong physiological activities, such
      as vasoconstriction and the enhancement of vascular permeability. Therefore, it
      is likely that these metabolites are involved in cerebral circulatory disturbance
      and the formation of brain edema in cerebral ischemia. It is reported that
      intracerebral injection of leukotriene B4, C4, and E4 increased blood-brain
      barrier permeability. Thus, it is suggested that leukotrienes may induce
      vasogenic cerebral edema. We examined role of the products resulting from
      arachidonic acid of the cyclo-oxygenase and lipoxygenase pathways on the
      formation of ischemic cerebral edema in rats with focal cerebral ischemia. Focal
      cerebral ischemia was induced by the occlusion of right middle cerebral artery.
      Acyclo-oxygenase inhibitor, indomethacin (4mg/kg), was given intravenously 30
      minutes before the occlusion of the middle cerebral artery. Also, azerastine
      hydrochloride (8mg/kg), which has an inhibitory effect on the production and
      release of leukotrienes from human neutrophil as well as an antagonistic action
      on leukotrienes and another inhibitory effect on the production of superoxide
      anion, was given intravenously 5 minutes prior to occlusion. Concentrations of
      prostaglandin E2 (PGE2), thromboxane B2 (TxB2), 6-keto-prostaglandin F1 alpha (6
      keto-PGF1 alpha) and leukotriene C4 (LTC4) measured by radioimmunoassay. The
      percent water content of a cerebral hemisphere was determined by the wet-dry
      weight method. In the occluded hemisphere, PGE2, 6-keto-PGF1 alpha, TxB2 and LTC4
      significantly increased at 2, 6, 12 hours respectively, following the MCA
      occlusion as compared to the control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136200
TI  - [Symptomatology and diagnostic criteria of brain death].

PMID- 8136199
TI  - [The detection of anti-Purkinje cell antibody (anti-Yo antibody) by ELISA using
      recombinant Yo fusion protein].
AB  - Paraneoplastic cerebellar degeneration (PCD) is a remote effect of cancer
      mediated by possibly immunological mechanisms. The sera and cerebrospinal fluid
      of PCD patients containing high titer autoantibody against cerebellar Purkinje
      cells had been reported. This antibody binds to 62-kD and 34-kD bands of
      cerebellar Purkinje cell homogenates (anti-Yo antibody). However, it is not
      always true that the autoantibody of this character on immunoblot and
      immunohistochemistry recognizes the same molecule. Recently, the DNA sequence
      encoding the Yo antigen, whose common epitope is a sequence containing leucine
      zipper motif, was reported. We made the recombinant protein deduced from the cDNA
      clone encoding the leucine-zipper motif of the Yo antigen. Using this recombinant
      protein as the antigen for ELISA, the anti Yo antibodies in the sera and CSF were
      examined and 3 new patients with PCD possessing anti-Yo antibody were found. The
      sera of one patient, serially taken during several kinds of treatment were
      examined with this ELISA system, which revealed that the anti-Yo antibody titer
      was increased after plasmapheresis and reduced after tumor resection and anti
      cancer chemotherapy. The early resection of malignant tumors may prevent the
      continuous production of high titer anti-Yo antibody and stop the progression of
      cerebellar tissue damage.

PMID- 8136201
TI  - [Evidence for the existence of L-dopa-immunoreactive neurons in the human
      mesencephalic region].
AB  - The existence of L-3,4-dihydroxyphenylalanine (L-DOPA) immunoreactivity is
      demonstrated for the first time in some neurons in the human mesencephalic
      region, using an immunohistochemical method with a newly raised, highly specific
      anti-L-DOPA antiserum. In this study, we have found many L-DOPA-positive/dopamine
      (DA)-positive neurons. On the other hand, we observed a few L-DOPA-positive/DA
      negative cell bodies in the dopaminergic regions in the midbrain. The present
      results suggest the possibility of the existence of more than one neuronal group
      in the human mesencephalic ventral tegmental area region. L-DOPA in one group is
      an intermediate metabolite for decarboxylation to DA and in another group may
      exist as an end-product. L-DOPA in the latter group could be a neuromodulator
      and/or neurotransmitter. Thus, we suggest that L-DOPA plays an important role
      besides being an intermediate of DA in the human mesencephalon.

PMID- 8136202
TI  - [CSF dynamics in the patients with syringomyelia associated with Chiari's
      malformation--quantitative analysis on cine MRI].
AB  - In a series of 12 patients with syringomyelia associated with Chiari's
      malformation, the authors quantitatively analyzed cerebrospinal fluid (CSF)
      dynamics in the subarachnoid space of the craniospinal junction, using cine MRI
      combined with pre-saturation method. In most of subjects, cine MRI revealed (1)
      decreased or increased maximum velocity of CSF in the caudal direction and (2)
      disturbed CSF motion in the caudal direction (delayed % cardiac cycle) in the
      craniospinal junction, strongly suggesting disturbed CSF dynamics in the
      craniospinal junction because of the tonsilar herniation. Of 12 subjects, 8
      patients underwent foramen magnum decompression and 4 underwent syringo
      subarachnoid shunt (SS shunt). In the patients who showed marked collapse of
      syrinx after foramen magnum decompression, follow-up cine MRI revealed the
      normalization of % cardiac cycle, representing postoperative improvement of CSF
      dynamics in the craniospinal junction. On the other hand, % cardiac cycle did not
      improve significantly in the patients who did not show marked collapse of the
      syrinx or suffered from meningitis after surgery. Significant changes were not
      observed in the patients who underwent SS shunt. In summary, these results
      suggested that cine MRI combined with pre-saturation method could detect the
      pathophysiological changes and evaluate the efficacy of the surgery, especially
      foramen magnum decompression, in the patients with syringomyelia associated with
      Chiari's malformation.

PMID- 8136203
TI  - [Multiple sclerosis with syringomyelia--case report].
AB  - A 32-year-old woman experienced subacute onset of weakness in her left leg,
      urinary retention and difficulty in extending her right middle and third finger.
      She subsequently suffered episodes of myelopathy, optic neuritis and cerebellar
      ataxia over a period of several years. Brain MRI showed multiple areas of high
      signal intensity on T2-weighted images, consistent with multiple sclerosis (MS).
      However spinal MRI revealed no abnormal findings. In her most recent episode, at
      age 40 she developed paraparesis. Neurologic examination revealed down beat
      nystagmus on gazing to the right, horizontal jerk nystagmus gazing to the left,
      weakness of the right middle and third fingers and paraparesis associated with
      spasticity of the right leg. Sensory disturbance below C3 and diminished
      vibration and position sense in both legs were also observed. The patient could
      not stand or walk, and urinary disturbance was present. Spinal MRI revealed
      syrinx formation at the level of vertebral bodies C2 to C6. The syrinx within the
      cervical cord diminished in size after four months, but the patient was unable to
      walk unaided and had moderate sensory disturbance as before. This finding
      suggests that the prognosis of MS with syrinx formation following repeated
      episodes of myelopathy is not always favorable. We believe that functional
      recovery in MS with syringomyelia is affected by the severity of the
      demyelination and/or gliosis caused by MS rather than by the presence of the
      syrinx.

PMID- 8136204
TI  - [Thoracic solitary neurenteric cyst--case report].
AB  - A 61-year-old man presented with repeated back pain and progressive anesthesia of
      both lower limbs. MR images and myelography showed an intradural, extramedullary
      tumor at the Th8-9 level. Surgery revealed a thin membrane containing
      xanthochromic cerebrospinal fluid behind the spinal cord. Microscopically, the
      excised lesions contained columnar epithelium with goblet cells. Spinal
      neurenteric cysts are a rare anomaly, especially solitary cysts located in the
      thoracic spine. The neurenteric canal transiently develops in the lumbosacral
      region during the 3rd week of gestation. Thus, it is difficult to claim that the
      neurenteric cyst in our case originated in a remnant of the neurenteric canal. As
      Bentley and Smith (1960) suggested, thoracic solitary neurenteric cysts may
      develop from a remnant of adhesion between ectoderm and endoderm during the 3rd
      week of gestation as a result of splitting of the notochord.

PMID- 8136205
TI  - [Presenile dementia with marked recent memory disturbance--in relation to
      hippocampal dementia].
AB  - Two cases of presenile dementia with marked recent memory disturbance were
      reported. Patient 1 is a 54-year-old woman. She noticed forgetfulness at the age
      of 51 years. Neurological examination at aged 52 revealed marked recent memory
      disturbance, but examination by WAIS (Wechsler Adult Intelligence Scale) showed
      good results (verbal IQ 106, performance IQ 104, total IQ 106). There was neither
      disorientation in place nor character change. Cranial CT scan and MRI revealed
      the absence of brain atrophy. About 3 years after the onset of the disease, the
      degree of dementia is slight and disorientation in place does not appear. Patient
      2 is a 67-year-old man. He noticed forgetfulness at the age of 63 years.
      Neurological examination at aged 66 revealed marked recent memory disturbance,
      but examination by WAIS-R showed moderate results (verbal IQ 89, performance IQ
      87, total IQ 88). There was neither disorientation in place nor character change.
      Cranial CT scan and MRI revealed slight dilatation of the inferior horns of the
      lateral ventricle and slight cortical atrophy. About 4 years after the onset of
      the disease, the degree of dementia was slight and disorientation in place did
      not appear. We can not rule out the possibility that our cases belong to
      Alzheimer's disease, but the clinical course of our cases is peculiar. In the
      relation of responsible lesion in pure amnestic syndrome, hippocampal dementia,
      and simple senile dementia, our cases are interesting and important.

PMID- 8136206
TI  - Our place in primary dental care.

PMID- 8136207
TI  - 1994 Year of Oral Health.

PMID- 8136208
TI  - What every dentist should know about practice purchase.
AB  - Anyone considering the purchase of a dental practice should heed the 'caveat
      emptor' maxim since there is a serious risk of dental practice bankruptcy in the
      present economic environment. To minimise this risk, the purchaser must be
      equipped with the necessary knowledge and information to ensure purchase terms
      are sound. This article aims to give guidance on how to assess value and
      associated risks in the purchase of goodwill and equipment, and sets out the main
      points to consider in evaluating a practice account prior to acquisition.

PMID- 8136209
TI  - 'Safety and effectiveness of fluoridation'.

PMID- 8136210
TI  - 'Active learning in the UK'.

PMID- 8136211
TI  - 'Active learning in the UK'.

PMID- 8136212
TI  - 'Orthodontics in the GDS'.

PMID- 8136213
TI  - A question of fluorides.

PMID- 8136214
TI  - The provision of prostheses for patients with severe limitation in opening of the
      mouth.
AB  - The problem of providing prostheses for patients with restricted mandibular
      opening is not well reported, either in current texts on prosthodontics or in the
      literature. This report features two patients who suffer from severe and chronic
      forms of the disorder. The aim of the article is to provide some useful hints
      with respect to the prosthetic management of such patients.

PMID- 8136215
TI  - Dental visiting behaviour and experiences of men with HIV.
AB  - To ascertain the dental visiting behaviour and experiences of men with HIV
      infection but without AIDS, a self-complete questionnaire was administered to
      convenience samples of men attending two genito-urinary medicine clinics. A total
      of 146 men completed questionnaires between December 1991 and June 1992. Of
      these, 85% had been regular or occasional attenders before diagnosis, 16% had not
      been to a dentist since diagnosis and 51% had changed their dentist. Although 63%
      had been to a general dental practitioner (GDP) at least once since diagnosis,
      half of them had withheld their HIV status at some time to obtain treatment. Of
      the 33% who had told their GDP of the diagnosis, half had been refused or offered
      limited treatment. The most common reasons for changing dentist, not visiting or
      withholding HIV status were concerns about the attitudes of the dental team and
      about confidentiality. Although regular oral examinations are of special
      importance to people with HIV their access to dental care is limited by their
      perceptions of dentists and the reported behaviour of dentists.

PMID- 8136216
TI  - Primary malignant melanoma of the oral cavity: a review of eight cases.
AB  - A review of oral malignant melanoma and data of eight patients are presented. The
      dismal prognosis of the condition is probably mainly due to its long, 'silent'
      course. In one-third of cases melanosis precedes the tumour--it is this condition
      that should alert clinicians. Therefore, pigmented oral lesions should be viewed
      with suspicion and biopsy is mandatory when the clinical diagnosis is uncertain.
      Early detection is essential to successful treatment. In spite of aggressive
      treatment modalities, survival in patients with advanced stage disease remains
      poor.

PMID- 8136217
TI  - The practice conference.
AB  - More general practitioners are acknowledging the reality that general practice is
      a business that has to be run on business lines. This does not imply any
      subversion, such as a lowering of clinical standards or less patient care, but it
      does imply the continuous implementation of business skills and their
      development. This article takes an innovative look at practice staff meetings--by
      suggesting the whole practice goes on a sales conference.

PMID- 8136218
TI  - Patients with and without oral malignancy in Pakistan. A dental elective report.
AB  - As part of the undergraduate course, final year students are encouraged to
      undertake a 2 week elective study, in order to gain a deeper insight into a
      chosen branch of dentistry. Since we both had an interest in oral medicine, we
      decided to carry out a small project on oral cancer.

PMID- 8136219
TI  - That vacant look.
AB  - Archaeologists delight in discovering ancient dustbins and waste tips because of
      the valuable information that can be gleaned about day to day life. Classified
      job adverts fulfil a similar function.

PMID- 8136220
TI  - Service agreements: clarifying departmental patient-focused care systems.

PMID- 8136221
TI  - A team approach to facilities planning and design.

PMID- 8136223
TI  - 21st century nurse executives: preparing for the future.

PMID- 8136222
TI  - A CQI model for operations improvement.

PMID- 8136224
TI  - The immune system: your defensive partner and offensive foe.
AB  - Immune function and inflammation are normal physiologic processes essential to
      health and well-being. However, overactivity of any inflammatory or immune
      responses can result in tissue-damaging reactions that threaten the functional
      integrity of tissues and organs. This article reviews the normal defense
      responses of inflammation and immune function as well as selected conditions
      resulting from offensive or hyperactive inflammatory and immune responses. The
      selected conditions include those seen more often in the acute and critical-care
      setting, such as tissue-damaging inflammation, drug allergy, autoimmunity, and
      transplant rejection.

PMID- 8136225
TI  - Risking infection: an issue of control for liver transplant recipients.
AB  - Liver transplantation is a technologic advancement that prolongs and improves the
      quality of life for people with liver disease. Loss of control over one's body
      and life is a feeling that begins with the diagnosis of liver disease. This study
      used a hermeneutic phenomenologic approach to investigate a liver transplant
      recipient's experience. A dimension of control was revealed within the
      description of the transplant experience. In an effort to maintain some control,
      the recipients adjusted the times of their immunosuppressive medications and
      continued to expose themselves to situations that could increase their risk of
      infection. Understanding the individual's experience and the implications for
      nursing are described.

PMID- 8136226
TI  - Sternal wound infections.
AB  - Sternal wound infections are a major cause of morbidity and mortality in patients
      undergoing cardiac surgery. They occur in 1% to 3% of patients who undergo open
      heart surgery and carry a 20% to 40% mortality rate. Sternal infections can range
      from minor, superficial infections to open mediastinitis with invasion of the
      sternum, heart, and great vessels. Staphylococcus species are responsible for the
      majority of sternal infections, but environmental sources can cause infections by
      other organisms. The common signs and symptoms of mediastinitis are fever,
      leukocytosis, sternal instability, drainage, and pain. Several risk factors exist
      for sternal wound infection, with bilateral internal mammary artery bypass
      grafting in diabetic patients being the most common. Treatment entails surgical
      debridement with either closed irrigation, open-wound packing, or muscle or
      omental flap procedures, as well as antibiotic therapy. Some simple procedures
      help limit the development of sternal infections in certain patients.

PMID- 8136227
TI  - Results of the consensus conference on fostering more humane critical care:
      creating a healing environment. Society of Critical Care Medicine.
AB  - The Society of Critical Care Medicine (SCCM) sponsored the Consensus Conference
      on Fostering More Human Care Creating a Healing Environment in October 1990 at
      Snowbird, Utah. The purpose of this conference was to address the challenges of
      providing sensitive, humane critical care in an increasingly technological and
      cost-conscious environment. The long-term objective was to develop this document
      (initially published by SCCM in 1992) as a resource for critical care
      professionals who are seeking methods by which to foster more humane care of
      their acutely ill patients.

PMID- 8136228
TI  - The dying patient in the intensive care unit: assisting the family in crisis.
AB  - Critically ill patients belong to larger phenomenologic systems, their families.
      What affects one member affects other system members. Nursing care requires
      meticulous observation and assessment of family concerns, understanding of
      clinical events, and practical experience to achieve positive outcomes even if a
      death occurs. It seems easy to dismiss the family from the clinical and technical
      matters of the critical care unit, especially when much nursing energy goes into
      operating peripheral machinery, performing tasks, and pursuing ever-changing
      patient-centered goals. The following case study attempts to redefine and
      redirect the focus of what "patient-centered" means to include the nurse, the
      patient, and the family in the meaning of the core of family-centered care.

PMID- 8136229
TI  - Do critical care nurses face burnout, PTSD, or is it something else?: getting
      help for the helpers.
AB  - The critical-care environment can be a stressful place to work. As a result of
      stress generation, critical-care nurses must use coping mechanisms not normally
      needed. The Adaptation Process Phenomenon describes a sequence of behavioral
      patterns and responses during stressful situations, perceived or not, that can
      result in negative behavioral responses to stress. For critical-care nurses,
      negative responses can impair the ability to care for patients and families.
      Adaptation to stress must be identified and examined as a potential illness for
      critical-care nurses. Is the problem burnout, post traumatic stress disorder, or
      something else.

PMID- 8136230
TI  - High-dose steroid therapy offers improvement in spinal cord injuries.
AB  - A spinal-cord injury can alter every aspect of a victim's life. Despite continued
      improvements in mortality associated with a spinal-cord injury, until recently
      little progress had been made in improving neurologic function. This paper
      reviews the development of steroid therapy for spinal cord injuries, the
      mechanisms of action, and the nursing care associated with its use.

PMID- 8136231
TI  - Phrenic nerve pacing--an alternative to positive pressure ventilation: the
      required nursing care.
AB  - Phrenic nerve pacing as a method of ventilation was first recognized in 1783. For
      years, this technique was not used because of the lack of practical technology.
      Interest in phrenic nerve pacing was renewed in the 1960s with the development of
      a radio frequency transmission system. Applicable to a limited patient
      population, phrenic nerve pacing has several benefits over positive-pressure
      ventilation. Benefits include greater patient mobility, verbal articulation, less
      mechanical noise, and breathing by natural negative-pressure. This article
      provides information for nurses who care for patients ventilated by phrenic nerve
      pacing.

PMID- 8136232
TI  - [The surgical prevention of pulmonary embolism in femoral-iliac-caval
      thrombosis].

PMID- 8136233
TI  - [Idiopathic hepatic adenoma in the adult].
AB  - Hepatic adenoma is an infrequent evenience, not wellknown till oral contraceptive
      diffusion in the 60s. The lesion may also be associated to the use of androgenic
      steroids, and to both type I and type III glycogen storage disease. Hepatic
      adenoma may be single or, more rarely, multiple. Recently the term of multiple
      adenomatosis has been adopted for the cases in which ten hepatic adenomas or more
      are found in a single liver. In this report, a case of hepatic adenoma involving
      a patient with no risk factors for such lesion as well as diagnosis and therapy
      are illustrated.

PMID- 8136234
TI  - [Cystic lymphangioma of the retroperitoneum. A case report].
AB  - Cystic lymphangioma of the retroperitoneum is a primary mesodermal derived benign
      neoplasm, arising from retroperitoneal lymphatics. The Authors report a case of
      cystic lymphangioma of the retroperitoneum recently observed, and a review of the
      international literature registering 181 cases from 1958 up to nowadays.
      Retroperitoneal localization, sub-clinic evolution and the impossibility to
      preoperatively define the histological type of the tumour, in spite of the modern
      diagnostic techniques, explain the difficulties to reach a correct differential
      diagnosis. The authors conclude that surgery only allows to exactly localize the
      tumour, yet the definition of cystic lymphangioma is an histological goal.

PMID- 8136235
TI  - [Acute ileitis due to Ascaris lumbricoides].
AB  - The authors report their experience of two cases of acute ileitis with an
      obstructive complication due to "Ascaris lumbricoides". The distinctive features
      were, in the first case, the pathogenic mechanism responsible of the occlusion,
      and in the second one, the need of a long term follow-up. The latter, especially
      in the "aspecific forms", often allows an etiological diagnosis difficult even at
      laparotomy. Indicating the most frequent causes of surgical complications found
      in ileitis, which is a medical disease easily curable by medical and dietetic
      means, the authors confirm the difficulties of an etiological diagnosis and
      surgical treatment, increased by the rarity of the disease.

PMID- 8136236
TI  - [Acute complications of pulmonary hydatidosis. Apropos 44 cases].
AB  - The authors examine a series of 44 patients with an acute complication of the
      hydatid disease of the lung. Clinical data, diagnostic features, surgical
      procedures and short and long term results are compared with those of 80 cases
      presenting no complications. Acute complication has in many cases a non specific
      clinical presentation and its evidence can only be found by means of radiology.
      The basic principles of surgical treatment are the same of the non complicated
      cysts, even though resection is more often performed (56.8%) since contextual
      lung and bronchial involvement is frequent. The authors report no significant
      difference between short- and long-term results in the two series.

PMID- 8136237
TI  - [Primary torsion of the omentum].
AB  - The primary torsion of the omentum is an exceptionally rare cause of acute
      abdomen. The authors, after reporting a case recently observed, discuss the still
      unknown aetiopathogenetic aspects, point out the problems of diagnosis and
      finally suggest the most correct surgical approach to avoid relapses or disregard
      pieces of necrotic omentum.

PMID- 8136238
TI  - [Bouveret's syndrome].
AB  - Bouveret's syndrome is represented by an intestinal occlusion due to a gallstone
      passed through a cholecysto-duodenal fistula and impacted in the duodenum. The
      authors report a case of this rare syndrome and discuss the optimal surgical
      approach.

PMID- 8136239
TI  - [Leiomyosarcoma of the gallbladder: a clinical case].
AB  - A case of primary leiomyosarcoma of the gallbladder is reported together with a
      review of the literature. The nonspecific clinical picture of the disease and the
      consequent high frequency of misdiagnosis are stressed. Cholecystectomy combined
      with chemotherapy and radiotherapy is the treatment of choice suggested.

PMID- 8136240
TI  - [The implantation of a heterologous prosthesis in reparative abdominal-thoracic
      surgery. Experience with the use of clindamycin in preventing prosthesis-related
      infection].
AB  - The authors point out how infection of heterologous prosthesis, widely used in
      surgery, can be a dramatic event. On the other hand, antibiotic prophylaxis is
      difficult because of the difference between "in vitro" and "in vivo" activity of
      many antibiotics, due to the production, by many bacteria, of the so-called
      glycocalyx. This would allow bacteria to clump and adhere to many surfaces,
      forming micro-colonies, causing delay in phagocytosis, and reducing the efficacy
      of antibiotics. On the basis of their, although limited, experience, the authors
      suggest, for the prophylaxis of prosthesis infection, the use of antibiotics such
      as clindamycin, able to reduce glycocalyx production.

PMID- 8136241
TI  - British Association for Cancer Research and Association of Cancer Physicians
      annual meeting. Birmingham, 27-30 March 1994. Abstracts.

PMID- 8136242
TI  - Thought play.

PMID- 8136243
TI  - Community care: mobility in store.

PMID- 8136244
TI  - Chemoembolisation: treating liver cancer.
AB  - This article describes the technique of chemoembolisation in the treatment of
      liver cancer and relates the underlying principles to the physiology of the
      liver. It also discusses some of the controversies now surrounding
      chemoembolisation.

PMID- 8136245
TI  - APL/APEL: bringing the theory to practice.

PMID- 8136246
TI  - International mobility: in permanent decline?

PMID- 8136247
TI  - Patients' perceptions of nurse uniforms.
AB  - This qualitative study was designed to discover what patients think of the
      uniforms worn by nurses in general practice, and whether they make a difference
      to the interactions between a patient and nurse. The results showed that a modern
      version of the traditional nurse's uniform is acceptable to most patients,
      especially for 'tasks and procedures'. Patients saw this aspect of a nurse's work
      as a lower priority than providing help, information and advice in a readily
      accessible manner, and for this a less traditional and more 'normal' outfit was
      more acceptable.

PMID- 8136248
TI  - The impact of change on violent patients.
AB  - This article describes how a continuing care ward attempted to deal with an
      increase in levels of violence towards staff and looks at how changes that were
      taking place on the ward may have contributed to a reduction in this problem.
      Possible lessons for the future management of this group of patients and
      reduction of violence are drawn from the discussion.

PMID- 8136249
TI  - Accommodation: flat scare.

PMID- 8136250
TI  - Sister Susie. Lights, camera, traction!

PMID- 8136251
TI  - NHS counter culture.

PMID- 8136252
TI  - Quip lash.

PMID- 8136253
TI  - Computer reviews. Nice vital statistics.

PMID- 8136254
TI  - [The gentle care of the premature--a new way].

PMID- 8136255
TI  - [A critical voice on the conventional care of the premature. Commentary to Edith
      Huebmer's contribution on the gentle care of the premature].

PMID- 8136256
TI  - [Supporting society for the incorporated Neuwerk children's hospital. Initiative
      of the Monchengladbach community for hospitalized children].

PMID- 8136257
TI  - [Respiratory therapy--treatment possibilities in pediatric nursing].

PMID- 8136258
TI  - [Contrast media in the diagnosis of digestive system disorders in children-
      potential use and risks].

PMID- 8136259
TI  - [Pediatric nursing in the home].

PMID- 8136260
TI  - [Pertussis vaccination for older children. Information from the Federal Health
      Department].

PMID- 8136261
TI  - [Curative treatments for children paid for by health insurance carriers].

PMID- 8136262
TI  - Immunotoxins for the treatment of leukaemia.

PMID- 8136263
TI  - Interleukin-4 inhibits apoptotic cell death and loss of the bcl-2 protein in B
      chronic lymphocytic leukaemia cells in vitro.
AB  - When monoclonal B cells from B-chronic lymphocytic leukaemia (B-CLL) patients are
      cultured in vitro, they die by apoptosis. Apoptotic cell death occurred in the B
      cells from 20/24 B-CLL patients after 26-30 h in in vitro culture, with 14.3
      59.0% (mean 33.6%) of their DNA being fragmented in approximately 180 base pair
      multimers. After 8-10 d culture, 90-100% of the B-CLL cells were dead. Cell death
      and DNA fragmentation were inhibited in the presence of 0.5-5 ng/ml human
      recombinant interleukin-4 (IL-4) and viable monoclonal B cells could be
      maintained in culture up to 3 weeks. At 5 ng/ml, IL-4 reduced  DNA fragmentation
      after a 26-30 h culture to 2.2-33.3% (mean 14.9%). IL-4 inhibited apoptosis
      without stimulating cell proliferation. In four patients the cells were resistant
      to apoptosis in vitro and they could be maintained for up to 4 weeks in culture
      medium alone. DNA fragmentation in all patients was increased in the presence of
      the RNA synthesis inhibitor actinomycin-D. Western blot analysis of cell lysates
      showed expression of the bcl-2 protein in all 11 B-CLL patients studied. However,
      during culture, bcl-2 protein levels were preserved only in patients resistant to
      apoptosis and were reduced in those susceptible to apoptosis. Reduction of bcl-2
      protein levels was inhibited in cells cultured in the presence of IL-4. These
      data offer an explanation for the difference between the long life in vivo and
      rapid death in vitro of B-CLL cells and indicate that IL-4 may participate in the
      extended survival of these non-dividing cells in vivo.

PMID- 8136264
TI  - Lack of IL-1 secretion from human myeloma cells highly purified by immunomagnetic
      separation.
AB  - This paper describes a method for purification of human myeloma cells.
      Mononuclear cells from six bone marrow samples and one pleural fluid sample from
      multiple myeloma patients were incubated with B-B4, a monoclonal antibody that is
      specific for plasma cells, and the B-B4+ cells were isolated using monosized
      magnetic beads coated with sheep anti-mouse Ig. With this positive selection
      method it was possible to achieve primary cultures with more than 99% myeloma
      cells. The average viability of these cultures was 81%. The B-B4 antibody did not
      alter proliferation or cytokine production of the myeloma cell lines U-266 and
      JJN-3. The B-B4+ myeloma cultures did not produce IL-1 and made only small
      amounts of IL-6 (< 93 pg/ml), whereas the cells remaining after extraction of the
      B-B4+ cells produced IL-1 (89-350 pg/ml) and large amounts of IL-6 (520-17,000
      pg/ml). This indicates that the B-B4+ myeloma cells are not directly responsible
      for the overproduction of these cytokines in multiple myeloma. This separation
      technique gave higher purity of myeloma cells than has been previously reported
      for any negative selection method and is recommended when high culture purity is
      of critical interest.

PMID- 8136265
TI  - Immortalization and characterization of human cell lines with mast cell and
      monocytic properties.
AB  - We have previously derived a cell strain which had both mast cell and monocytic
      properties from the bone marrow of a child with diffuse cutaneous mastocytosis.
      This cell strain, termed HBM-M, consisted of two cell populations both of which
      possessed certain ultrastructural, cytochemical and surface phenotypic features
      of degranulated mast cells. The cells also displayed cytochemical and surface
      phenotypic features of monocytes. These cells may represent a common bone marrow
      derived mast cell/monocyte precursor. Studies of human mast cells have been
      hindered by the fact that it is difficult to establish such cells in long-term
      culture. Thus, we sought to immortalize HBM-M cells by introducing Simian virus
      40 large T-antigen. Following transfection by the strontium phosphate technique,
      transformed cells were selected, expanded and passaged until the cells entered a
      non-proliferative phase termed crisis. Certain clones passed through crisis 3
      months later and by this means two immortal cell lines, HBM-MI-1 and HBM-MI-2,
      were obtained. The criterion for immortality was growth for greater than 100
      population doublings. The immortal cell lines retained some, but not all, of the
      mast cell and monocytic properties of the original HBM-M cell strain. The
      immortalization of the cell strain HBM-M provides an opportunity to investigate
      the mast cell and monocytic properties of these cells, and the apparent
      relationship between mast cells and monocytes.

PMID- 8136266
TI  - Interleukin 4 prevents the induction of tissue factor mRNA in human monocytes in
      response to LPS or PMA stimulation.
AB  - Increased expression of tissue factor (TF) procoagulant activity by blood
      monocytes and tissue macrophages is implicated in a number of thrombotic
      disorders, as well as in fibrin deposition associated with inflammatory lesions
      and immunological diseases. We found that interleukin 4 (IL-4), a T lymphocyte
      derived cytokine known to regulate a number of monocyte functions, inhibited the
      production of TF by monocytes in response to endotoxin and phorbol myristate
      acetate (PMA) in vitro. IL-4 had a concentration-dependent inhibitory effect on
      functional TF procoagulant activity (PCA) and reduced the binding of an anti-TF
      antibody, as assessed by flow cytometry analysis. Moreover, IL-4 reduced LPS- and
      PMA-induced TF mRNA levels. TF mRNA stability was not modified by IL-4 after the
      arrest of transcription by actinomycin D. We thus conclude that mRNA suppression
      is mediated by an effect occurring at the transcriptional level. Our results also
      show that the suppressive effect of IL-4 is independent of an increase in the
      intracellular concentration of cyclic AMP, another established inhibitor of TF
      production. Locally produced IL-4 might thus contribute to limiting the
      consequences of monocyte activation.

PMID- 8136267
TI  - Establishment of a leukaemic cell line from a patient with acquisition of
      chromosomal abnormalities during disease progression in myelodysplastic syndrome.
AB  - A cell line designated SKM-1 was newly established from leukaemic cells of a 76
      year-old Japanese male patient with monoblastic leukaemia following
      myelodysplastic syndrome (MDS). The cells were obtained from peripheral blood of
      the patient when he lost multiple point mutations of ras genes with acquisition
      of chromosomal abnormalities during disease progression in MDS. The cells grew as
      a single floating cell, and have been continuously growing with the morphological
      characteristics of immature monoblasts by serial passages during the past 42
      months with a doubling time of about 48 h. By cytochemical analysis, the cloned
      cells were positive for butyrate esterase, but negative for the Epstein-Barr
      virus associated nuclear antigen. Phenotypic analysis revealed the expression of
      myelomonocyte specific antigens such as CD4, CD13, CD33 and HLA-DR. Cells from
      the primary peripheral blood and those from 50 passages of the SKM-1 cell line
      both possessed no activated ras genes but showed karyotype abnormalities with
      46,XY, del(9)(q13;q22), der(17) t(17;?)(p13;?). The SKM-1 cells have two
      mutations in p53 gene and overexpress the p53 products. This cell line may
      contribute to a better understanding of molecular mechanisms in the progression
      from MDS to myelogenous leukaemia.

PMID- 8136268
TI  - PML/RAR alpha fusion gene is expressed in both granuloid/macrophage and erythroid
      colonies in acute promyelocytic leukaemia.
AB  - Acute promyelocytic leukaemia (APL) associated with a t(15;17) translocation
      generates a PML/RAR alpha chimaeric gene which is transcribed as a fusion PML/RAR
      alpha mRNA. To clarify the pathophysiologic role of PML/RAR alpha in APL
      patients, we examined the expression of PML/RAR alpha in haemopoietic colonies in
      five patients with APL by reverse transcriptase polymerase chain reaction (RT
      PCR) analysis. By the two-step RT-PCR method, we demonstrated that PML/RAR alpha
      positive clones were present in progenitor cells including both CFU-GM and BFU-E
      in two cases. This result suggests that the translocation of PML/RAR alpha
      occurred in a pluripotent stem cell in some APL patients. In four patients we
      detected two amplified cDNA fragments of 780 and 640 bp which presumably arose by
      alternative splicing of the PML gene. Interestingly, of CFU-GM and BFU-E colonies
      examined in four patients, there were three different types of colonies: those
      expressing only the 780 bp fragment, those expressing only the 640 bp fragment,
      and those expressing both fragments. This suggests that alternative splicing was
      clonally determined in each colony. We describe a useful RT-PCR technique for the
      study of gene expression in a limited number of haemopoietic precursor cells.

PMID- 8136269
TI  - Expression of CD45RA (naive) and CD45RO (memory) antigens in T-acute
      lymphoblastic leukaemia.
AB  - We have determined the distribution of CD45RO (memory) and CD45RA (naive)
      antigens in the bone marrow blasts from 25 patients with T-acute lymphoblastic
      leukaemia (T-ALL). Four groups of patients were identified on the basis of
      reactivity with specific antibodies by flow cytometric analysis: (a) CD45RA
      /CD45RO+ (16 patients): four CD4-/CD8+, seven CD4+/CD8+ and five CD4-/CD8-; (b)
      CD45RA+/CD45RO- (three patients): three CD4-/CD8-; (c) five CD45RA-/CD45RO-: one
      CD4+/CD8-; one CD4-/CD8+; three CD4+/CD8+; (d) CD45RA+/CD45RO+ (one case):
      CD4+/CD8-. There was no correlation between the expression of the naive and the
      memory phenotypes and the presence of CD4, CD8 or any other antigen except the
      CD10 antigen which was expressed by all CD45RA-/CD45RO- patients. The
      predominance of the CD45RA-/CD45RO+ phenotype (65%) and the low incidence of the
      hybrid phenotype CD45RA+/CD45RO+ (5%) in T-ALL, differs from the results reported
      by others for chronic or prolymphocytic T-cell leukaemias, in which the
      simultaneous expression of these maturational antigens was detected in
      approximately half of the cases.

PMID- 8136270
TI  - Cytogenetic studies in splenic lymphoma with villous lymphocytes.
AB  - We report the cytogenetic findings on 31 cases of splenic lymphoma with villous
      lymphocytes (SLVL). TPA stimulated cells from peripheral blood (28 cases), spleen
      (two cases) and lymph node (one case) with SLVL have been analysed. A clonal
      chromosome abnormality was found in 27/31 patients (87%); this was identified as
      a simple abnormality in 12 cases and a complex one in 15. Four recurring
      abnormalities were seen: t(11;14)(q13;q32) in five patients, deletions or
      translocations involving 7q in seven patients, iso 17q in four patients and
      translocations involving 2p11 in four patients. The high frequency of clonal
      chromosome abnormalities in SLVL contrasts with the usually benign clinical
      course of this disease. Abnormalities found frequently in patients with chronic
      lymphocytic leukaemia (CLL) such as trisomy 12 and deletions or translocations
      involving 13q14 were each seen in only one patient. No case had the t(14;18)
      characteristic of follicular lymphoma. Our findings demonstrate the high
      frequency of clonal and often complex chromosome abnormalities in SLVL. Although
      a unique chromosome rearrangement has not been identified, a pattern of four
      recurrent abnormalities has emerged. Our results suggest that SLVL is distinct on
      cytogenetic grounds from B-CLL and follicular lymphoma but shows similarity with
      mantle cell lymphoma, lymphoplasmacytic lymphoma and B-PLL.

PMID- 8136271
TI  - Japanese B cell chronic lymphocytic leukaemia: a cytogenetic and molecular
      biological study.
AB  - Clinical, cytogenetic, and molecular genetic studies were performed to clarify
      the pathophysiology of Japanese B cell chronic lymphocytic leukaemia (B-CLL),
      since the incidence of B-CLL in Japan is significantly lower than in western
      countries. The clinical and laboratory features of 55 Japanese patients with B
      CLL in this study did not differ from those of Americans or Europeans with B-CLL.
      In the chromosome analyses, suitable metaphases with good band quality were
      obtained from 48 patients (87.2%), of whom 22 patients (45.8%) showed clonal
      chromosome aberrations and 14 (29.2%) had non-clonal aberrations. Trisomy 12 and
      abnormalities of 14q and 13q were found in four (18.2%), two (9.1%) and six
      patients (27.2%), respectively. There were no particular chromosome abnormalities
      or specific breakpoints in Japanese B-CLL. However, complex karyotype was found
      in higher incidence than in western countries. In the Southern blot analyses,
      rearranged band patterns were observed in the major breakpoint region (mbr) of
      the bcl-2 gene in one case, in the 5'-breakpoint region (5'-bcl-2) in two, and
      bcl-3 in one. Of the two patients with 5'-bcl-2 rearrangements, one had a normal
      karyotype and the other had t(2;18)(p12;q21). The incidence of rearrangements of
      the bcl-1, bcl-2 and bcl-3 genes in Japanese B-CLL was similar to that in western
      countries. These findings suggest that the biological characteristics of B-CLL in
      Japan are almost the same as those in western countries, although the incidence
      of B-CLL in Japan is quite different; this may be related to racial differences,
      which seem to be an important factor in the development of B-CLL.

PMID- 8136272
TI  - Altered expression of the retinoblastoma susceptibility gene in chronic
      lymphocytic leukaemia.
AB  - The pathogenesis of chronic lymphocytic leukaemia (CLL) is unknown. One of the
      most frequent cytogenetic abnormalities in CLL is a deletion within the long arm
      of chromosome 13, the region to which the retinoblastoma (Rb) gene has been
      mapped. Lack of Rb expression has been linked to the carcinogenic process in many
      human tumours. We therefore sought to investigate the role of Rb gene
      inactivation in CLL using differential polymerase chain reaction on reverse
      transcribed RNA. The result of the PCR was quantitated using HPLC. 5/39 patients
      revealed a lack or significantly impaired expression of the Rb gene upon
      differential PCR analysis. In addition, immunocytochemical studies were performed
      using the Rb-specific monoclonal antibody PMG245. 10/56 patients showed a weak or
      absent expression upon immunocytochemical analysis compared to monocytes or
      granulocytes. The samples lacking Rb were from both early and late stage CLL. Our
      results indicate that inactivation of the Rb protein occurs in a fraction of CLL
      cases and can be found in early and late stages of the disease.

PMID- 8136273
TI  - Multiple myeloma: 'early' plasma cell phenotype identifies patients with
      aggressive biological and clinical characteristics.
AB  - The immunological phenotype of bone marrow myeloma cells and peripheral blood
      lymphocytes was evaluated in 38 untreated myeloma patients. A striking increase
      of monotypic cells expressing the same light chain as the M component was
      observed in bone marrow from 18/38 (47%) patients. A two-colour analysis
      clarified that the majority of myeloma cells co-expressed plasma cell and B
      lymphocyte markers (cyIg, CD38, CD56 and sIg), and were regarded as early-plasma
      cells (early-PC). In the remaining patients, myeloma cells expressed plasma cell
      markers only (late-PC). Phenotype corresponded to a distinct morphological
      pattern: early-PC showed a lympho-plasmocytoid feature with significantly lower
      diameters than late-PC (12.1 v 14.8 microns, P < 0.007). Moreover, the plasma
      cell labelling index was significantly increased in early-PC patients (1.2 v
      0.5%, P < 0.04). In peripheral blood from patients with early-PC, monotypic cells
      co-expressing sIg and CD38, CD56, but not CD19, were also detected. These data
      suggest a recirculation of early-PC. Myeloma cells maintained their phenotypic
      pattern during the course of the disease. This observation suggests that the
      degree of maturation is an intrinsic characteristic of the myeloma cell
      population in individual patients. The evaluation of prognostic factors, such as
      beta 2-microglobulin, C-reactive protein and neopterin, showed a statistically
      significant increase in the early-PC patients, suggesting a poor outcome. In
      conclusion, myeloma cell phenotype allows identification of a myeloma variant
      with aggressive biological and clinical characteristics.

PMID- 8136274
TI  - A novel dysfunctional protein C (protein C Padua 2) associated with a thrombotic
      tendency: substitution of Cys for Arg-1 results in a strongly reduced affinity
      for binding of Ca++.
AB  - A dysfunctional protein C (PC) molecule (Protein C Padua 2) was found in a 40
      year-old man presenting with recurrent deep vein thrombosis/pulmonary embolism
      and a family history of thrombotic disease. The patient exhibited a normal PC
      antigen level, normal chromogenic activity (using Protac as PC activator) but
      markedly reduced coagulometric activity. After adsorption of patient plasma onto
      Al(OH)3, between 30% and 45% PC antigen/chromogenic activity but no coagulometric
      activity was detectable in the supernatant. The dysfunctional molecule exhibited
      reduced affinity for a Ca++ dependent anti-protein C monoclonal antibody as
      detected by specific ELISA assay. Immunoblotting experiments showed that PC Padua
      2 had an increased MW (95 kD v 65 kD for normal PC). The lesion responsible was
      determined by PCR/direct sequencing to be a heterozygous CGT/TGT transition in
      exon 3 of the protein C gene resulting in the substitution of Arg by Cys at
      residue--1 in the pro-peptide leader sequence. The presence of a high MW PC was
      consistent with the fact that (part of) the propeptide (at least Cys-1) still was
      attached to the protein C molecule. This finding could also explain the strongly
      reduced affinity of PC Padua 2 for the Ca++ dependent anti-protein C monoclonals.

PMID- 8136275
TI  - Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and
      human factor V.
AB  - We report on a 34-year-old woman whose plasma showed a marked prolongation of
      thrombin time (TT) (> 200 s) using bovine thrombin. The patient had previously
      been exposed twice to topical bovine thrombin contained in fibrin glue during
      cardiac surgery. TT was normal when human thrombin was used as reagent. The
      patient's purified IgG reacted with bovine prothrombin and bovine thrombin in
      immunoblotting studies but showed virtually no cross-reaction with human
      thrombin. In addition, following surgery, factor V clotting activity (FV:C) was
      reduced to 9% of normal. The inhibitor of bovine thrombin persisted over a period
      of more than a year, while the level of FV:C progressively returned to normal
      within this time period. Development of thrombin and FV:C inhibitors was also
      investigated in plasma of 34 consecutive patients who had undergone either
      cardiac surgery or neurosurgery with use of fibrin glue containing bovine
      thrombin. Eleven of 24 patients after cardiac surgery and two of 10 patients
      after neurosurgery presented with TT > or = 25 s (normal plasma 15 s). Two
      patients had been re-exposed to fibrin glue during cardiac re-operation and
      showed markedly prolonged TT (> 60 s). All 13 patients who had acquired a
      thrombin inhibitor also had low FV:C activity (10-60% of normal plasma), whereas
      FV:C activity remained in the normal range in the 21 patients with normal TT. Our
      findings indicate that development of inhibitors of bovine thrombin as well as co
      immunization to factor V occurs frequently and is associated with the amount of
      applied fibrin glue and with the type of operation. Re-exposure to fibrin glue
      seems to enhance formation of inhibitors of bovine thrombin and human factor V.

PMID- 8136276
TI  - Decreased contact factor mediated fibrinolysis in cirrhosis.
AB  - We studied extrinsic and intrinsic fibrinolysis in 20 patients with cirrhosis
      (nine mild/moderate, group 1; 11 severe, group 2) and 19 normal controls to
      define the role of intrinsic (contact factor medaited) fibrinolysis in cirrhosis.
      Global plasma fibrinolytic activity (fibrin plate lysis) was similar in all
      groups. Dextran sulphate activated contact factor mediated fibrinolysis was
      decreased in group 2 (median 95.2%) compared with group 1 (121.0%) and controls
      (131.7%). Tissue plasminogen activator antigen (t-PA Ag) levels were increased in
      group 2 (28.2 ng/ml) compared both with group 1 (8.5 ng/ml) and controls (5.9
      ng/ml). Plasma t-PA activity was raised in group 2 (5.50 IU/ml) and group 1 (5.25
      IU/ml) versus controls (0.82 IU/ml). Plasminogen activator inhibitor-1 (PAI-1 Ag)
      levels were raised in group 2 (28.0 IU/ml) versus controls (8.5 IU/ml) but PAI
      activity was similar in all groups. Factor XII activity was decreased in group 2
      (48.76 u/dl), but not group 1, versus controls (89.1 u/dl). Prekallikrein
      activity was decreased both in group 2 (27.27 u/dl) and group 1 (33.01 u/dl)
      versus controls (108.59 u/dl) and was lower in group 2 than group 1. C1-esterase
      inhibitor chromogenic activity was decreased in group 1 (102.30 u/dl) and group 2
      (58.76 u/dl) versus controls (116.24 u/dl). The normal global fibrinolytic
      activity despite increased t-PA activity may be due to a concomitant increase in
      PAI. The decreased intrinsic fibrinolysis in severe cirrhosis, unaccompanied by a
      rise in C1-esterase inhibitor, may be explained by the decreased factor XII and
      prekallikrein activity. These changes are probably due to reduced liver cell
      mass.

PMID- 8136277
TI  - A base substitution (T-->C) in codon 29 of the alpha 2-globin gene causes alpha
      thalassaemia.
AB  - We have identified three individuals of Greek or Greek Cypriot origin with an
      atypical form of HbH disease characterized by a severe hypochromic microcytic
      anaemia associated with relatively small amounts of HbH in the peripheral blood.
      Molecular analysis has shown that each is a compound heterozygote for a
      previously described mutation affecting the poly A addition signal (AATAAA-
      >AATAAG) and a previously undescribed mutation involving a T-->C transition in
      codon 29 of the alpha 2 gene causing a leucine-->proline substitution. Although
      this mutation would be expected to produce an unstable haemoglobin and hence a
      haemolytic anaemia, simple heterozygotes for the alpha 29Leu-->Pro mutation have
      the phenotype of alpha-thalassaemia trait.

PMID- 8136278
TI  - Coexistence of hereditary spherocytosis (HS) due to band 3 deficiency and beta
      thalassaemia trait: partial correction of HS phenotype.
AB  - A kindred with hereditary spherocytosis and beta-thalassaemia trait was
      identified. Detailed studies of the red cell membrane proteins on polyacrylamide
      gels with sodium dodecyl sulphate (SDS-PAGE) demonstrated the presence of band 3
      (anion transporter) deficiency in all HS subjects (20-25% reduction) whereas
      spectrin content was in the normal range. The molecular defect of beta
      thalassaemia in this kindred was due to a beta(0) codon 39 (C-T) mutation, as
      assessed by beta globin gene amplification and ASO-probe hybridization. Seven
      subjects of this family were studied: two were normal, two had HS alone, two co
      inherited HS and beta-thalassaemia trait, and one had beta-thalassaemia trait
      only. The two subjects with HS alone had a typical clinical form of spherocytosis
      with anaemia, reticulocytosis and increased red cell osmotic fragility. The two
      with both HS and beta-thalassaemia trait were not anaemic and showed a small,
      well-compensated haemolysis. Hence the finding of red cells with abnormalities of
      both HS and beta-thalassaemia indicates that beta-thalassaemic trait 'silences'
      HS caused by band 3 deficiency.

PMID- 8136279
TI  - Cytokine gene expression in peripheral blood mononuclear cells during graft
      versus-host disease after allogeneic bone marrow transplantation.
AB  - Cytokine gene expression in peripheral blood mononuclear cells during the
      development of graft-versus-host disease (GVHD) in patients who underwent
      allogeneic bone marrow transplantation (allo BMT) was analysed using a
      semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The
      expression of interleukin (IL)-1 beta, IL-6, and tumour necrosis factor (TNF)
      alpha mRNA was increased during the development of GVHD and the degree of this
      increment depended on the severity of the disease. IL-2 expression was not
      detected at all and interferon-gamma expression was not much changed during GVHD.
      In patients with hepatic veno-occlusive disease (VOD), another transplantation
      related complication, the expression of IL-1 beta and TNF-alpha mRNA was
      increased but IL-6 mRNA expression showed little increase. These findings suggest
      that IL-1 beta, IL-6 and TNF-alpha produced by peripheral blood mononuclear cells
      play an important role in the development of GVHD. Furthermore, liver dysfunction
      due to GVHD or VOD may be distinguishable by this type of cytokine analysis.
      Analysis of cytokine mRNA expression in peripheral blood mononuclear cells after
      allogeneic bone marrow transplantation may provide important information
      concerning the immune response and the cytokine network system in marrow
      transplant patients.

PMID- 8136280
TI  - Circulating immune complexes involving the ABO system after platelet transfusion.
AB  - It has been proposed that when ABO unmatched platelets are transfused circulating
      immune complexes (CIC) may be formed between the patient's soluble ABH antigens
      and the transfused antibodies. Platelets might then be destroyed by bystander
      mechanisms or by the binding of CIC to the Fc receptor or to C3 binding membrane
      proteins on the platelet. An ELISA C1q assay was used to detect CIC in 40
      patients with haematological diseases who had received multiple platelet
      transfusions. A significantly larger number of refractory patients were positive
      (41%) in the assay than non-refractory patients (13%) or normal blood donors
      (0%). The presence of circulating IgG anti-A was sought in six group A refractory
      patients who had been transfused with ABO unmatched platelets. To determine
      whether the IgG anti-A was monomeric or in high molecular weight complexes, the
      serum was fractionated by gel exclusion chromatography and fractions were tested
      for the presence of IgG anti-A. In all six patients the peak of IgG anti-A
      binding occurred in fractions of high molecular weight (200-900 kD). Five out of
      six patients also demonstrated anti-A activity in fractions corresponding to
      monomeric IgG (about 150-180 kD). Fractions containing high molecular weight anti
      A were purified using a protein G column and the eluates were tested for the
      presence of group A antigen using dot immunoblotting. Group A antigen was
      associated with the purified IgG anti-A in 4/5 patients tested. Appropriate
      transfused and non-transfused controls had no anti-A in any fractions. Although
      not unexpected, these studies demonstrate for the first time that refractory
      patients receiving ABO unmatched platelets have CIC composed of ABO antigens and
      their corresponding antibodies present in their serum that circulate for at least
      several days. It also confirms the hypothesis that some CIC in haematological
      patients are induced by transfusion.

PMID- 8136281
TI  - Cytomegalovirus infection in leucocytes after bone marrow transplantation
      demonstrated by mRNA in situ hybridization.
AB  - Cytomegalovirus (CMV) infection in leucocytes after bone marrow transplantation
      (BMT) was identified using a 35S-labelled antisense RNA probe specific for CMV
      immediate early (IE) gene mRNA. 54 patients were examined regularly up to 14
      weeks after BMT. 36 after allogeneic BMT and 18 after autologous BMT. Only
      mononuclear cells with monocyte morphology were CMV IE mRNA positive. The number
      of CMV positive leucocytes was higher after allogeneic BMT than after autologous
      BMT (P = 0.006), and in patients with acute graft-versus-host disease (GvHD) II
      IV than with GvHD O-I (P = 0.06). In patients who later developed chronic GvHD,
      the mean value of CMV infected leucocytes during the first week after BMT was
      higher than in patients without chronic GvHD (P = 0.034). Patients with
      symptomatic CMV infection had greater numbers of CMV infected leucocytes during
      the fourth and fifth week after BMT than patients without CMV disease, but the
      difference did not reach statistical significance. CMV infection of monocytes may
      be an important factor in the early onset of CMV infection and of GvHD.

PMID- 8136282
TI  - Molecular basis of clinical and morphological heterogeneity in hereditary
      elliptocytosis (HE) with spectrin alpha I variants.
AB  - The impaired ability of spectrin dimers to self-associate into tetramers is one
      of the most frequent defects associated with hereditary elliptocytosis (HE) and
      its more serious form, hereditary pyropoikylocytosis (HPP). We previously
      described four proteic variants of the spectrin (Sp) alpha I tryptic domain
      associated with the Sp dimer self-association defect (Sp alpha I/78, Sp alpha
      I/74, Sp alpha I/65, Sp alpha I/46 variants). Following the characterization of
      proteic variants, genomic molecular defects were identified and most of the
      mutations appeared to lie either in or near the self-association site, i.e. in
      the alpha I tryptic domain or in the beta I tryptic domain. The clinical severity
      of these different mutations varies considerably and ranges from asymptomatic to
      severe haemolytic disease such as in heterozygous HPP patients and in some
      homozygous HE patients. Studies of 113 patients from 61 HE families showed a
      correlation among parameters and showed which factors modulate the clinical
      expression of the molecular defect. Our analysis indicated that the clinical
      expression was directly correlated with the severity of the spectrin dimer self
      association defect as evaluated by the increase in the Sp dimer percentage found
      in the 4 degrees C extract. A critical threshold of 40-50% of unassembled Sp
      dimer was determined; above that, patients exhibited severe haemolysis requiring
      splenectomy. The percentage of Sp dimer depends, in turn, on two factors: (i) the
      nature of the variant in relation to the position of the mutation versus the
      tetramerization site; (ii) the relative amount of mutant spectrin present in the
      membrane (ranging from 15% to 80% in heterozygous patients). As for the severity
      of haemolysis, the ghost mechanical stability to shear stress, as measured by
      ektacyometer, was also found to depend on the Sp dimer self-association defect.
      In contrast, the decrease in erythrocyte deformability was not related to the
      amount of unassembled Sp dimer but appeared to be correlated with the amount of
      mutant spectrin whatever the variant. Concerning erythrocyte morphology and the
      number of elliptocytes, the Sp alpha I/65 variant appears to be the most
      'elliptocytogenic' variant, indicating that erythrocyte shape abnormality is not
      linked to the Sp dimer self-association defect.

PMID- 8136283
TI  - Seasonal changes in red blood cell parameters.
AB  - Seasonal changes in blood count (haematocrit and haemoglobin values) have been
      described in studies of small samples. Since Israel is characterized by high
      summer temperatures, we attempted to determine whether there are circannual
      changes in blood count, and how they are influenced by mean monthly temperature.
      In a cross-sectional study, venous blood was drawn from 4317 male employees in
      industry aged 20-64 years. Blood count values were analysed by month. To estimate
      possible changes in serum osmolality, serum electrolytes were also examined.
      Values of haemoglobin and haematocrit in August were significantly lower than
      during the rest of the year. Circannual rhythms explained between 10% and 57% of
      the variances of all the variables as assessed by cosinor rhythmometry, although
      they had wide confidence intervals and most were not statistically significant.
      The lower mean haematocrit in August reflected reduction in mean corpuscular
      volume (MCV) rather than a decrease in red blood cell count (RBC). The change
      observed in haematocrit and haemoglobin in August is possibly related to heat
      acclimatization rather than to endogenous sinusoidal circannual rhythms. Both
      plasma and red cell volume expansion appear to occur. Possible seasonal changes
      should be taken into account in evaluation of blood counts.

PMID- 8136284
TI  - Serial phenotypic, cytogenetic and molecular genetic studies in Richter's
      syndrome: demonstration of lymphoma development from the chronic lymphocytic
      leukaemia cells.
AB  - In this report we describe a unique longitudinal study on the clinical,
      phenotypic, cytogenetic and molecular genetic features of malignant cells from
      diagnosis of chronic lymphocytic leukaemia (CLL) to the development of lymphoma
      and lymphomatous meningitis. CLL cells at diagnosis were CD5+, CD19+, surface
      IgG+, kappa+, were karyotypically abnormal and showed clonal rearrangements in
      the immunoglobulin heavy (IgH) and kappa light chain genes. Phenotypically
      leukaemic cells and lymphoma cells at RS resembled CLL at diagnosis, but showed
      cytogenetic evolution. Geometrically leukaemic cells and lymphoma cells retained
      the initial clonal rearrangements in IGH and kappa genes, but showed additional
      supervening clonal rearrangements in both of these genes as the disease
      progressed to RS. Furthermore, the c-lambda DNA showed clonal rearrangements in
      the leukaemic cells and lymphoma cells at RS. This complete phenotypic and
      genotypic analysis of tumour cells during the course of the disease demonstrates
      the origin of lymphoma from CLL cells through progressive cytogenetic and
      molecular genetic changes in CLL cells.

PMID- 8136285
TI  - Thalassaemic osteoarthropathy treated with radiotherapy.
AB  - Patients with beta thalassaemia may develop a specific osteoarthropathy involving
      the feet. A number of different treatments for this condition have been tried,
      including rest, analgesia and hypertransfusion. We report a case of a patient
      with thalassaemic osteoarthropathy who responded to radiotherapy after failing
      conventional treatment.

PMID- 8136286
TI  - Pure red cell aplasia of pregnancy: a distinct clinical entity.
AB  - We describe a 31-year-old patient with pure red cell aplasia of pregnancy,
      successfully managed with regular blood transfusions. In vitro studies showed
      specific inhibition of day 14 erythroid colonies (BFU-E) using serum and purified
      immunoglobulin G (IgG) obtained from the patient at diagnosis (before blood
      transfusion). The inhibition of BFU-E disappeared when haematological remission
      occurred 3 weeks after delivery and she remains clinically well with a normal
      haemoglobin 4 years later.

PMID- 8136287
TI  - Parvovirus B19 induced red cell aplasia in myelofibrosis.
AB  - A 38-year-old female presented with moderate anaemia and a leucoerythroblastic
      blood film. Subsequent investigation showed myelofibrosis in cellular phase. Her
      haemoglobin quickly and spontaneously recovered with concurrent serological
      evidence of recent parvovirus B19 infection. This is the first report in the
      literature of parvovirus causing red cell aplasia in myelofibrosis.

PMID- 8136288
TI  - BCR rearrangement in apparent essential thrombocythaemia.
AB  - The presence of the Philadelphia chromosome is a major determinant of the
      prognosis of patients with myeloproliferative disorders. We describe a case of
      apparent essential thrombocythaemia in whom cytogenetic analysis was normal.
      However, the presence of basophilia, the absence of abnormal megakaryocytes in a
      trephine biopsy and the female sex of the patient prompted Southern analysis of
      peripheral granulocyte DNA. This revealed a BCR rearrangement and the patient has
      therefore undergone allogeneic bone marrow transplantation. This case emphasizes
      the importance of both cytogenetic and molecular analysis of patients with
      apparent essential thrombocythaemia.

PMID- 8136289
TI  - Clonal chromosomal abnormalities in Fanconi's anaemia: what do they really mean?
AB  - Patients with Fanconi's anaemia (FA) have aplastic anaemia, leukaemia,
      myelodysplasia and tumours. Since leukaemia has a very poor prognosis, it is
      desirable to identify high-risk patients. To determine the significance of clonal
      marrow chromosomal abnormalities we began a prospective study in 17 patients:
      five were normal, eight aplastic, and four myelodysplastic. Three of 11 with
      adequate cytogenetics had transient abnormal clones. None had leukaemia at 3-24
      months. Changing cytogenetic patterns may not be related to leukaemic evolution
      in patients with a DNA repair defect.

PMID- 8136290
TI  - Parvovirus B19-related lymphadenopathy.
AB  - We tested whether parvovirus B19 (PVB19) is involved in benign lymph node
      swelling as a causative agent. The serum specimens from 13 patients with lymph
      node swelling of unidentified cause were tested for IgM and IgG antibody against
      PVB19 by Western blot analysis. Five patients had IgM antibody, and PVB19 DNA was
      detected in the serum from one of them by dot-blot analysis, suggesting the
      recent PVB19 infection and its involvement in lymph node swelling of these
      patients. Clinical and haematological features of the patients are also
      discussed.

PMID- 8136291
TI  - Aplastic anemia and ticlopidine.

PMID- 8136292
TI  - Skin reaction with low molecular weight heparins.

PMID- 8136293
TI  - Correction of the DNA synthesis defect in vitamin B12 deficiency by
      tetrahydrofolate using the dU suppression test.

PMID- 8136294
TI  - Binding of beta 2-glycoprotein I to platelet-derived microparticles.

PMID- 8136295
TI  - Nuclear accessory factors enhance the binding of progesterone receptor to
      specific target DNA.
AB  - The human progesterone receptor (PR) is dependent upon hormone and a nuclear
      accessory factor(s) for maximal binding to progesterone response elements (PRES)
      in vitro. Recombinant full-length PR, expressed in a baculovirus system and
      purified to apparent homogeneity, was used as a substrate to isolate and identify
      the accessory factor(s). The major PRE binding enhancement activity present in
      nuclear extracts was shown to be associated with the high mobility group
      chromatin protein HMG-1. Moreover, HMG-1 was equally effective in enhancing the
      DNA binding of both the A and B isoforms of PR. Enhancement of PRE binding was
      highly selective for HMG-1 as a single purified protein and was not mimicked by a
      general protein stabilization effect. In gel mobility shift assays, it appeared
      that HMG-1 enhanced PRE binding without stably participating as a component of
      the final DNA-PR complex, suggesting that HMG-1 acts indirectly by modifying the
      PR protein or the target DNA. HMG-1 is a sequence-independent DNA binding protein
      that recognizes distorted DNA structures and is also able to promote further
      distortions by bending DNA. Enhancement of PRE binding was found to be intrinsic
      to the conserved DNA binding domain of HMG-1 suggesting that HMG-1 acts by
      promoting a structural alteration in the target PRE-DNA.

PMID- 8136296
TI  - Non-steroidal antiandrogens: synthesis and biological profile of high-affinity
      ligands for the androgen receptor.
AB  - New N-substituted arylthiohydantoin antiandrogens were synthesized. These
      compounds presented exceptionally high relative binding affinities (RBAs) for the
      rat androgen receptor (AR): up to 3 times that of testosterone (T) and 100 times
      the RBAs of non-steroidal antiandrogens such as flutamide, Casodex and Anandron.
      Furthermore, unlike available markers for AR, they were totally devoid of any
      binding to the other steroid receptors. RU 59063, the molecule with the highest
      RBA, was tritiated. When it was compared to [3H]T for the assay of rat, mouse,
      hamster and human AR, it gave rise to the same number of binding sites but its K
      alpha (6 x 10(9) M-1) for rat and human AR were, respectively 3 and 8 times
      higher than that of T. Moreover RU 59063, unlike T, was devoid of any specific
      binding to human plasma. In vivo, these compounds displayed antiandrogenic
      activity while being devoid of any agonistic effect. Thus, RU 56187, given orally
      in castrated male animals, prevented in a dose-dependent manner the effects of 3
      mg/kg testosterone propionate (TP) on mouse renal ornithine decarboxylase (acute
      test) and of 0.5 mg/kg TP on rat prostate weight (chronic test). In these two
      models, its ED50 was 0.6 and 1 mg/kg, respectively. In the intact rat, when given
      alone, it inhibited dose-dependently the effect of endogenous androgens on the
      seminal vesicles (ED50 approximately 1 mg/kg) and prostate (ED50 approximately 3
      mg/kg) weights. These results suggest that these new compounds may be useful as
      specific markers for the androgen receptor as well as for the treatment of
      androgen-dependent diseases or disorders such as prostate cancer, acne, hirsutism
      and male pattern baldness.

PMID- 8136297
TI  - Androgens regulate expression of the gene coding for a mouse vas deferens protein
      related to the aldo-keto reductase superfamily in epithelial cell subcultures.
AB  - Mouse vas deferens protein (MVDP), a member of the aldo-keto reductase
      superfamily, is exclusively produced in the vas deferens. To better understand
      androgen-regulated MVDP gene expression we have used RNA hybridization to study
      the effects of androgens on the steady-state levels of MVDP mRNA in vas deferens
      epithelial cell subcultures. Northern blot analysis revealed that these cells
      only express MVDP mRNA in the presence of androgens. There was a close
      relationship between MVDP mRNA levels and dihydrotestosterone concentrations.
      MVDP mRNA is induced over a period of 24h and maximal induction is about 25-fold.
      Treatment of cells with cycloheximide completely abolished the observed androgen
      effect suggesting that the induction of the MVDP gene by androgens depends on
      continuous protein synthesis. Transient transfection of vas deferens epithelial
      cells with MMTV-CAT vector showed that these cells contained functional androgen
      receptors and that they are a suitable system to study androgen effect on MVDP
      gene regulatory elements.

PMID- 8136298
TI  - The effect of androgens and antiandrogens on the immunohistochemical localization
      of the androgen receptor in accessory reproductive organs of male rats.
AB  - The androgen receptor (AR) was localized immunohistochemically after different
      hormonal treatments in the ventral prostate, coagulating gland, seminal vesicle
      and epididymis of the adult rat. In the untreated controls AR-immunoreactivity
      was confined to the cell nuclei. One week after castration or treatment with the
      gonadotropin-releasing hormone antagonist Cetrorelix (150 micrograms/animal per
      day) a cytoplasmic staining occurred in the epithelial cells of the ventral
      prostate and in part of the coagulating gland and seminal vesicle. In contrast,
      the AR remained exclusively in the nuclei in the epididymal epithelium and the
      glandular smooth muscle layer even after 2 weeks of androgen depletion. Bolus
      injections of either dihydrotestosterone (1 mg/kg), the antiandrogen flutamide
      (40 mg/kg), or the novel non-steroidal antiandrogen casodex (40 mg/kg) to
      androgen-depleted animals eliminated cytoplasmic AR-immunoreactivity and restored
      the nuclear staining pattern in the ventral prostate. A sustained 2-week
      treatment with the antiandrogens resulted in a loss of weight in all organs but
      did not alter the distribution of AR-immunoreactivity. The data show an apparent
      cytoplasmic/nuclear ligand-dependent translocation of the AR in the ventral
      prostate, coagulating gland and seminal vesicle but not in the epididymis of the
      adult rat.

PMID- 8136299
TI  - Identification of the cysteine in the steroid-binding site of human
      corticosteroid binding globulin by site-directed mutagenesis and site-specific
      chemical modification.
AB  - Binding of corticosteroids by human corticosteroid binding globulin (hCBG) is
      thought to involve interaction with one of its two cysteine residues (Cys60 and
      Cys228). To identify which of the two cysteine residues mediates steroid binding,
      we have produced mutant hCBGs containing serine or alanine in place of Cys228 by
      site-directed mutagenesis. Alteration of Cys228 to serine or alanine does not
      change the steroid binding affinity of hCBG, demonstrating that Cys228 is not
      involved in the binding interaction. This finding strongly suggests that Cys60 is
      the functionally important cysteine. By modifying the wild-type and mutant hCBGs
      with the sulfhydryl-specific reagents N-ethylmaleimide, iodoacetamide, and sodium
      tetrathionate, we have demonstrated that Cys60 is present at the steroid binding
      site, and that it may be directly involved in steroid binding. This result also
      identifies Cys60 as the accessible cysteine reported in previous studies.

PMID- 8136300
TI  - Actions of steroid hormones- and growth factors on glial cells of the central and
      peripheral nervous system.
AB  - Primary cultures of oligodendrocytes and astrocytes and purified cultures of
      Schwann cells were prepared respectively from forebrain and sciatic nerves of
      newborn rats. The effects of steroid hormones and growth factors on glial cell
      growth and on the production of myelin-specific proteins and lipids were
      investigated. Progesterone (P, 100 nM) decreased the proliferation of glial cells
      of the central nervous system. This inhibitory effect of P was abolished by the
      simultaneous administration of the antagonist RU486, thus suggesting a receptor
      mediated action of the hormone. The expression of myelin-specific proteins,
      including the myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'
      phosphodiesterase (CNPase), and of a myelin-specific lipid, galactocerebroside
      (Gal C), was also measured during cell differentiation under different hormonal
      conditions. The expression of MBP in oligodendrocytes was increased by P, and
      this effect was not blocked by RU486. The combined application of P and insulin
      promoted a synergistic stimulation of MBP expression. Insulin, by itself, also
      increased the number of MBP-positive oligodendrocytes in culture. The effects of
      P and insulin appeared to be selective as dexamethasone, dehydroepiandrosterone,
      pregnanolone and epidermal growth factor (EGF) had no effect. Only estradiol (E2,
      500 nM) increased the number of MBP-immunoreactive cells, but in contrast to P,
      only a small synergism between E2 and insulin on MBP expression was observed. The
      expression of CNPase, another myelin-specific protein, was also increased by P
      and, here again, a synergy between P and insulin could be observed. In contrast,
      the expression of Gal C, a myelin-specific lipid, was not modified by P or other
      steroid hormones. Moreover, the increase in Gal C-positive cells observed in
      response to insulin alone was not further potentiated by P. Glial cells of the
      peripheral nervous system, namely Schwann cells, are also sensitive to steroid
      hormones. Schwann cells contain estrogen receptors, and E2 stimulates their
      proliferation in the presence of forskolin or dibutyryl cyclic AMP (dbcAMP). The
      mitogenic effect of E2 was abolished by the pure antiestrogen ICI-164,384.
      Insulin, at micromolar concentration, also stimulated Schwann cell growth when
      forskolin or dbcAMP were present in the culture medium. The mitogenic effect of
      insulin was mediated by insulin-like growth factor I (IGF-I) receptors. Indeed,
      at a physiological nanomolar concentration, IGF-I but not insulin or IGF-II,
      increased the proliferation of Schwann cells in synergy with forskolin. In
      addition, Schwann cells express receptors for IGF-I.

PMID- 8136301
TI  - 21-hydroxylase deficiency congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) results from an enzymatic block at any stage
      in the synthesis of cortisol. All enzyme defects causing CAH are autosomal
      recessive traits. It is a relatively common disease, occurring in 1 in 5000 to 1
      in 15,000 births in most populations. Since the isolation of the gene responsible
      for steroid 21-hydroxylase deficiency (involved in about 90% of the cases of CAH)
      in 1984, knowledge of the specific mutations that cause the different forms of
      CAH has grown rapidly. Defects in the encoding gene have been confirmed as the
      basis of endocrine disease in the case of all but one of the adrenal
      steroidogenic enzymes. Analysis of DNA obtained by chorionic villus sampling in
      early pregnancy permits prenatal diagnosis and treatment of 21-hydroxylase
      deficiency CAH. The correlation between the clinical expression of endocrine
      disease and the mutations of the primary structural gene is not absolute.
      Clinicians cannot accurately predict the course of the disease or make
      therapeutic decisions based on the genotype alone. We will review the various
      forms of clinical presentation of 21-hydroxylase CAH, its etiology, diagnosis,
      molecular genetics, and treatment.

PMID- 8136302
TI  - Importance of A/B and C domains of the estrogen receptor for its adsorption to
      hydroxylapatite.
AB  - Regulatory properties of estrogen receptor (ER) result from the existence of
      functional domains within its primary structure. Thus, A/B and C domains which
      are rich in tyrosyl residues control gene expression while the E domain confers
      estrogen binding capacity. Hydroxylapatite (HAP) is known to adsorb ER. Scatchard
      plot analysis of [3H]estradiol binding patterns of HAP batches to which cytosolic
      ER had been adsorbed revealed that AB and/or C domains are mainly responsible for
      this property. Thus, treatment of these batches with the tyrosine reagent
      tetranitromethane (TNM) led to a dramatic release of adsorbed receptors. This did
      not occur with ER preparations devoid of exposed ABC domains obtained by
      selective immunoextraction with H-226 anti-ER monoclonal antibody prior to HAP
      assay. KC1 treatment (500 mM) of HAP batches also led to a release of bound
      receptors especially those devoid of exposed ABC domains. Such binding
      characteristics were also found with full length and truncated ERs produced in
      yeast: the full length receptor strongly interacted with HAP while the truncated
      receptor devoid of AB and C domains displayed only a weak adsorption. Additional
      investigation revealed that estradiol binding to cytosolic ER does not modify its
      reactivity towards TNM.

PMID- 8136303
TI  - Regulation of glucocorticoid receptor (GR) mRNA and protein levels by phorbol
      ester in MCF-7 cells. Mechanism of GR mRNA induction and decay.
AB  - Treatment of MCF-7 cells with the phorbol ester 12-O-tetradecanoylphorbol-13
      acetate (TPA) (10(-7) M) was associated with a time-dependent increase in
      specific binding of [3H]dexamethasone (34.8 +/- 4.6 fmol/mg protein after 9 h of
      TPA treatment compared with 16.0 +/- 2.3 fmol/mg protein in control cells) as
      well as a transient induction in the level of glucocorticoid receptor (GR) mRNA
      (4- to 8-fold stimulation after 2-3 h, followed by a decline towards the control
      value after 6 h). In the presence of the transcription inhibitor actinomycin D
      (AMD) (5.0 micrograms/ml) the TPA-dependent induction of GR mRNA was completely
      abolished, and GR mRNA showed a gradual decline with a half-life of 2-3 h. In
      contrast, treatment with TPA and the protein synthesis inhibitor cycloheximide
      (50 microM) resulted in a superinduction of GR mRNA (> 50-fold after 6 h).
      Inhibition of a half-life of 2-3 h, which is identical to that observed in non
      treated cells. We conclude that the increase in GR mRNA in the presence of TPA is
      dependent on ongoing transcription, whereas the rate by which GR transcripts are
      degraded, is not altered by TPA.

PMID- 8136304
TI  - Affiliations among steroid receptors as revealed by multivariate analysis of
      steroid binding data.
AB  - To illustrate the informative value of descriptive multivariate analysis in
      biochemical screening, we have analyzed several data matrices relating to the
      binding of steroids to the estrogen, progestin, androgen, glucocorticoid and
      mineralocorticoid receptors in different organs and species. We first compared
      dendrograms of steroid hormone receptors, that were obtained by an automatic
      hierarchical classification analysis of the binding data, to published
      phylogenetic trees of nuclear receptors based on amino-acid sequence analysis.
      The former classification describes the affiliations among the receptors as given
      by the binding specificity of a population of 187 steroids in a traditional
      cytosol binding assay (an indirect comparison of ligand binding sites); the
      latter describes the affiliations among the receptors as given by a comparison of
      selected primary sequences involved in ligand-dependent regulation of
      transactivation and dimerization. A similar hierarchical classification was also
      performed on the binding data of 62 steroids to myometrium cytosol from different
      species in order to show to what extent the progesterone-binding proteins in
      these species are affiliated. Hierarchical clustering methods classify each type
      of variable (receptor or steroid) independently. In order to be able to correlate
      both types of variable (receptors and steroids) on single-display graphs, it is
      necessary to resort to correspondence factorial analysis (CFA). CFA ranks the
      information content within the experimental system, highlighting major
      correlations and disclosing secondary correlations by eliminating redundant
      information and background noise. This multivariate method, applied to the
      analysis of published data, illustrated the particular specificity of estrogen
      binding in human vagina and raised the question of the nature of the binding
      protein in this tissue. Our examples are based on small data tables that can and
      have been analyzed de visu. However, it is certain that such descriptive
      multivariate techniques are indispensable for the analysis of large data banks
      not only to define structure-activity relationships but to estimate the degrees
      of affiliation among the biological variables being measured. Knowledge of such
      affiliations will help to organize available information in a context where the
      complexity of the biological systems under study is becoming increasingly
      apparent.

PMID- 8136305
TI  - Modulation of calcium signaling and LH secretion by progesterone in pituitary
      gonadotrophs and clonal pituitary cells.
AB  - In estradiol-treated pituitary cells, progesterone enhances gonadotropin
      releasing hormone (GnRH)-induced LH secretion from cultured rat pituitary cells
      during short-term treatment but attenuates this response during prolonged
      treatment. In the present study, the effects of gonadal steroids on GnRH-induced
      cytoplasmic calcium ([Ca2+]i) responses in gonadotrophs were analyzed in rat
      pituitary cells and immortalized (alpha T3-1) murine gonadotrophs. Ca2+ responses
      were measured in cell suspensions and single gonadotrophs, loaded with Fura-2 or
      Indo-1, respectively, and pretreated for 48 h with 1 nM estradiol with or without
      100 nM progesterone, or for 48 h with 1 nM estradiol and then for 3 h with 100 nM
      progesterone. In cells of the alpha T3-1 gonadotroph lineage, GnRH elicited
      biphasic Ca2+ signals composed of an initial peak response followed by a
      prolonged plateau phase. The amplitudes of both the extracellular Ca(2+)
      independent spike phase and the extracellular Ca(2+)-dependent plateau phase were
      enhanced or inhibited by short- or long-term progesterone treatment,
      respectively. In single pituitary gonadotrophs, GnRH (0.5 nM) elicited
      oscillatory responses due to intermittent release and uptake of Ca2+ from
      intracellular stores. Treatment with progesterone shifted the oscillatory signal
      toward biphasic (3 h) or subthreshold (48 h) response profiles, revealing a
      steroid-induced change in the pattern of Ca2+ mobilization. In addition to these
      agonist-induced responses, the transient [Ca2+]i responses of pituitary cells and
      individual gonadotrophs to high K+ were enhanced or inhibited after short- or
      long-term progesterone treatment, respectively. These actions were correlated
      with the effects of progesterone on K(+)-induced LH secretion. The [Ca2+]i and LH
      secretory responses to phorbol ester treatment were also enhanced by short-term
      exposure of the cells to progesterone. The results demonstrate that the
      stimulatory and inhibitory effects of progesterone on agonist-induced Ca2+
      signaling result from changes in Ca2+ mobilization and entry, and contribute to
      the modulatory actions of the steroid on GnRH-induced LH secretion.

PMID- 8136306
TI  - RU 58841, a new specific topical antiandrogen: a candidate of choice for the
      treatment of acne, androgenetic alopecia and hirsutism.
AB  - A new topically active non-steroidal antiandrogen, RU 58841 has been synthesized.
      It displays high affinity for the hamster prostate and flank organ (F.O.)
      androgen receptors. In vivo, when topically applied, it exerts a potent dose
      dependent regression of F.O. area at a dose as low as 1 microgram/animal while
      being devoid of antiandrogenic activity on deep accessory sex organs and of any
      effect on testosterone level up to 100 micrograms/animal. In the same species,
      after subcutaneous administration, it induces at the dose of 300
      micrograms/animal, a small decrease in F.O. area equivalent to that of 1
      microgram applied topically and a weak systemic activity. In intact rats, no
      effects were observed up to 1 microgram/animal whatever the route of
      administration. These results suggest that RU 58841 might useful for the topical
      treatment of androgen-dependent skin disorders such as acne, androgenetic
      alopecia and hirsutism.

PMID- 8136307
TI  - Immunolocalization of retinoic acid receptors in rat, mouse and human ovary and
      uterus.
AB  - We raised an antibody against a synthetic peptide corresponding to amino acids
      155-174 of human retinoic acid receptor alpha (RAR-alpha). The sequence is highly
      homologous in all RARs and their isoforms. When mouse and human RARs (alpha, beta
      and gamma) expressed in Cos cell were analysed with immunoblot, all receptors
      gave a specific 51 K signal. Mouse RAR-gamma gave an additional signal
      corresponding to 58 K. In human teratocarcinoma cells (F9) both 51 and 58K
      molecule sizes were detected. The RAR expression in F9 cells was slightly down
      regulated in charcoal-stripped culture medium and returned to normal level after
      retinoic acid treatment. The 51 K protein was found in all ovarian and uterine
      samples, but the quantity of the 58 K protein varied in different species and
      organs, being highest in the mouse uterus and the rat and human ovary. Using
      immunohistochemistry the RARs were found in the nuclear compartment. In the rat
      uterus, positive immunoreaction was found mainly in the nuclei of epithelial,
      uterine glandular and stromal cells. In the rat ovary, positive reaction was
      found in the nuclei of germinal epithelial, follicular and stromal cells.

PMID- 8136308
TI  - In vitro interaction of uterine estrogen receptor with the estrogen response
      element present in the 3'-flanking region of the murine c-fos protooncogene.
AB  - Estradiol treatment rapidly stimulates transcription of the c-fos protooncogene
      in the rodent uterus, and transfection analysis previously identified an estrogen
      response element (ERE) in the 3'-flanking region of the murine gene with the
      sequence GGTCAnnnCAGCC. We now report that endogenous estrogen receptor (ER)
      obtained from either mouse or rat uterus binds to this 3'-ERE. Unoccupied
      receptor, receptor occupied with estradiol and receptor occupied with the
      antiestrogen tamoxifen all bind to this element, and the binding of receptor
      exhibits strict sequence specificity. By using a competition binding assay, the
      affinity of the ER for the c-fos-ERE is estimated to be approximately an order of
      magnitude less than the affinity for the consensus ERE (GGTCAnnnTGACC) found in
      the Xenopus and chicken vitellogenin genes. Differences in the electrophoretic
      mobilities of the c-fos and vitellogenin EREs bound to the ER in band-shift
      assays also suggest subtle structural differences in the two complexes. Mutations
      in either half-site of the c-fos-ERE destroy ER binding, suggesting that the
      receptor binds to this sequence as either a homo- or heterodimer. The 3'-fos-ERE
      region exhibits some homologies to both AP1 and AP2 consensus sites, but neither
      AP1-like proteins present in uterine extracts nor recombinant AP2 bind this
      protooncogene sequence. The finding that the ERE present in the 3'-region of the
      murine c-fos gene interacts with receptors present in the mouse and rat uterus
      supports a role for this element in the physiological regulation of c-fos
      expression in the uterus by estrogens.

PMID- 8136309
TI  - The effect of long-term glucocorticoid therapy on glucocorticoid receptor content
      and on steroid response to ACTH.
AB  - The effect of long-term glucocorticoid therapy for systemic diseases on
      glucocorticoid receptor (GR) content and on basal and ACTH-stimulated levels of
      plasma and salivary cortisol 17 alpha-hydroxy-progesterone, androstenedione, 11
      beta-hydroxyandrostenedione, DHEA, its sulfate and sex hormone-binding globulin
      (SHBG), as well as on basal levels of aldosterone, was investigated in a group of
      24 children treated with prednisone for at least 8 months. The therapy was
      interrupted 24 h before the ACTH test and before plasma and saliva sampling. The
      control group consisted of 21 healthy children of corresponding age and sex. The
      patients were divided into two subgroups with normal and subnormal basal
      cortisolemia, they also differed in their response to ACTH. The GR levels in
      patient groups were indistinguishable from those found in controls. No
      correlation was found between GR content and basal levels of the above steroids
      or their response to ACTH. The best markers, apart from basal cortisolemia, for
      evaluation of the degree of suppression of adrenal function appeared to be the
      response of salivary (but not of plasma) cortisol and 17 alpha-hydroxy
      progesterone to ACTH. Surprisingly, significantly lower levels of SHBG levels,
      which rose markedly after ACTH, were found in all the patients.

PMID- 8136310
TI  - Estrogenic and progestagenic activities coexisting in steroidal drugs:
      quantitative evaluation by in vitro bioassays with human cells.
AB  - The progestin-specific stimulation of alkaline phosphatase (AP) activity in cells
      of the T47D human breast cancer line was applied to the development of a
      sensitive microtiter plate bioassay for the quantitative evaluation of
      progestagenic and antiprogestagenic potencies of natural and synthetic compounds.
      Some of the steroids tested (viz. progesterone, medroxyprogesterone acetate,
      norethynodrel) behaved as full-agonists, capable of inducing AP activities to the
      same maximal levels (equal efficacy), while others (norethindrone, gestrinone,
      R5020, norgestrel, Org OD 14 and its 4-ene metabolite) behaved as partial
      agonists, eliciting lower maximal effects. Efficacy, EC50 values (concentrations
      at which they induce one-half of the maximal response) and "slope factors" serve
      to characterize agonistic effects. Relative progestagenic potencies among the
      full-agonists were evaluated by comparing EC50 concentrations. Several 19-nor
      synthetic progestins (norethynodrel, norethindrone, Org OD 14 and its 4-ene
      isomer, dl-norgestrel, levo-norgestrel, RU2323), but none of the tested
      progestins with the pregnane structure, showed intrinsic estrogenic activity, as
      evaluated by using a similar in vitro bioassay based on a previously reported
      estrogen-specific induction of AP in human endometrial adenocarcinoma cells of
      the Ishikawa Var-1 line. Maximal estrogenic effects of all the tested progestins
      with dual activity were as high as those of estradiol. However, these compounds
      widely varied in their EC50 values for estrogenic activity. Consequently, the in
      vitro bioassays can reveal differences in the ratio of progestagenic and
      estrogenic activities intrinsic to these compounds. The reduced capability of the
      partial agonists to exert progestagenic or estrogenic effects on AP expression
      may reflect an impeded, receptor-mediated action, a mechanism that would also
      account for their inhibitory effects on the induction of AP activity by full
      agonists. Partial progestagenic agonists were able to reduce the efficacy of a
      full agonist to their own partial maximal activity.

PMID- 8136311
TI  - Neopterin release by myeloid leukaemic cells can be synergistically augmented by
      1,25-dihydroxyvitamin D3 in combination with gamma interferon or granulocyte
      macrophage colony stimulating factor.
AB  - Neopterin is a pteridine molecule released by immune activated monocytes.
      Monocytic maturation may be induced in acute myeloid leukaemia (AML) blasts and
      the U937 leukaemic cell line by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], an effect
      which is augmented by both gamma interferon (IFN) or granulocyte-macrophage
      colony stimulating factor (GM-CSF). We have demonstrated that, while 1,25(OH)2D3
      and GM-CSF alone have little effect, both IFN and GM-CSF act synergistically with
      1,25(OH)2D3 to increase neopterin secretion in the U937 cell line. Neopterin
      secretion was associated with, but not necessarily dependent on, the degree of
      phenotypic differentiation achieved by cells. Neopterin secretion was also
      synergistically enhanced in AML blasts by the action of 1,25(OH)2D3 in
      combination with IFN but not GM-CSF; secretion was enhanced in AML blasts without
      concomitant evidence of phenotypic maturation. We have shown that the monocytoid
      cell line U937, under appropriate conditions, may secrete neopterin in response
      to stimulatory agents other than IFN. In addition, the distinct difference in the
      pattern of response to the combination of 1,25(OH)2D3 with GM-CSF compared with
      that of 1,25(OH)2D3 plus IFN suggests that the augmentation of 1,25(OH)2D3 effect
      by IFN and GM-CSF is mediated by separate mechanisms.

PMID- 8136312
TI  - Blood flow and vascular endothelial cell function.
AB  - Vascular endothelial cells (ECs) are not merely a selective permeability barrier
      between blood and underlying tissue but actively play an important role in
      maintaining homeostasis of circulation. ECs that have a variety of synthetic,
      metabolic, secretory and self-adaptive capabilities regulate vascular tonus and
      interact with other cells such as vascular smooth muscle cells and white cells.
      Recent evidence suggests that these functions are affected by shear stress on the
      endothelial wall, which is a rheological force shearing the luminal surface of
      the blood vessel when a viscous fluid such as blood flows over it. Wall shear
      stress reportedly regulates adaptive vessel growth and angiogenesis, and might be
      a local risk factor in the pathogenesis of atherosclerosis. Shear stress also
      modulates the production of vasoactive substances such as endothelium-derived
      relaxing factor, prostacyclin, histamine and endothelin, and regulates
      macromolecule permeability and endocytosis. More recent studies have shown that
      shear stress exerts an influence on the expression of mRNA such as tissue
      plasminogen activator mRNA. These facts suggest that ECs serve as
      mechanoreceptors by which changes in blood flow or shear stress are recognized by
      the EC and the signal is transmitted to intracellular organelles. It has been
      indicated so far that intracellular Ca2+ and the membrane potential might be
      involved in the shear stress-sensing mechanism of ECs. Knowledge of EC
      biomechanics, i.e. the EC response to shear stress, will help us to understand
      the mechanism not only of blood flow-dependent vessel growth and remodeling but
      also atherogenesis.

PMID- 8136313
TI  - How much work is expended for respiration?
AB  - The rate of work expended to move air in the respiratory system has been
      determined for five different airflow waveshapes, a non-linear respiratory model
      and five exercise levels. As expected, the rectangular waveshape was the most
      efficient. Model conditions were then changed one a time: (i) starting lung
      volume was allowed to vary, (ii) exhalation flow limitation was added, (iii)
      respiration was considered to be a metabolic burden determining part of the
      ventilation requirement and (iv) a respirator mask was added. Although there is
      no direct work advantage to varying initial lung volume, such volume changes
      appear to be dictated by the asymmetry of lung recoil pressure about the lung
      relaxation volume; allowing the work of respiration to become a metabolic burden
      clearly shows why respiratory waveforms change from rest to exercise; and, adding
      a respirator imposes a severe respiratory burden on the wearer engaging in
      moderate, heavy and very heavy exercise.

PMID- 8136314
TI  - Correlation dimension of heart rate variability: a new index of human autonomic
      function.
AB  - Correlation dimension analysis (CDA) of spontaneous heart rate variability in
      humans was performed with the use of autonomic blocking agents (propranolol and
      atropine) and postural change, and was compared with heart rate power spectral
      analysis (HRPSA). The correlation dimension was increased by the suppression of
      sympathetic activity and decreased by the suppression of parasympathetic
      activity. Atropine abolished the correlation dimension and the low- and high
      frequency components of HRPSA. With a postural change from supine to standing,
      the low- to high-frequency power ratio was significantly increased, indicating
      the augmentation of sympathetic activity or the reduction of parasympathetic
      activity, or both. Thus, it was suggested that a postural change from supine to
      standing causes the predominance of sympathetic activity. As this postural change
      decreased the correlation dimension, it was also indicated that the predominance
      of sympathetic activity may decrease the correlation dimension. CDA was superior
      to HRPSA in that the former method provided a measure of the effect of
      propranolol on the heart in the supine position, which could not be evaluated by
      the latter method. Thus, CDA of heart rate variability is a useful non-invasive
      tool for evaluating the autonomic balance.

PMID- 8136315
TI  - A comparative study of the quantification of REM occurrence patterns via REM
      density and REM time-connectivity.
AB  - In a previous study, we have shown that the use of a Markovian model and its
      associated state-transition probability matrices (STPMs) is a viable non-invasive
      approach to quantify the dynamics of REM occurrence patterns. This paper
      describes an attempt to compress the information conveyed by the STPMs into one
      single scalar parameter, defined as the time-connectivity of inter-REM intervals.
      This parameter was studied in conjunction with REM density, another global index
      of phasic REM activity during sleep, and the two were compared in terms of their
      variability with respect to subject, night of sleep recording and REM period rank
      in six healthy young subjects. The density index was found to be invariant to
      night of recording and REM period rank, but not with respect to subject. The time
      connectivity parameter index was found to be invariant will all three variables,
      yielding the same results as the use of STPMs. The invariance characteristics of
      both indices and the usefulness of using time-connectivity as a global descriptor
      of a possible underlying organizational structure in the REM generation process
      are discussed.

PMID- 8136316
TI  - Protein kinase C: biochemical characteristics and role in melanocyte biology.
AB  - The protein kinase C (PKC) family of proteins, consisting of at least ten
      isoforms, has been shown to regulate major cellular functions, including the
      growth and differentiation in many cell types. Use of PKC activators and
      inhibitors in combination with molecular biology techniques, has permitted
      detailed exploration of their specific intracellular actions. Recently, studies
      have implicated PKC specifically in the regulation of growth and differentiated
      function in melanocytes. In particular, the beta-isoform of PKC was shown to
      regulate human melanogenesis through activation of tyrosinase, the rate limiting
      enzyme in melanogenesis. This article reviews the role of PKC in melanocyte
      biology.

PMID- 8136317
TI  - Immunoblotting studies of linear IgA disease.
AB  - Patients with linear IgA deposits at the basement membrane zone (BMZ) detected by
      direct immunofluorescence (IF) may show diverse clinical and laboratory findings.
      The aim of this study was to investigate the issue of target antigens for linear
      IgA disease (LAD) antibodies. We examined sera from 46 adults and children with
      exclusive IgA deposits at the BMZ, by both indirect IF on 1 M NaCl split human
      skin and immunoblotting. IgA anti-BMZ antibodies binding to the epidermal side of
      the split were found in 31 LAD sera. IgA anti-BMZ antibodies binding to the
      dermal side of the split were detected only in 4 LAD sera. No sera contained IgA
      anti-BMZ antibodies binding to both sides of the split. Immunoblotting revealed
      that 12 epidermal side-positive LAD sera reacted with the 97 kDa protein in the
      human epidermal extracts. Moreover, we found that 2 dermal side-positive LAD sera
      reacted with a protein of approximately 255 kDa on immunoblotting of the dermal
      extract. We conclude that there are at least two types of LAD. However, the
      nature of target antigens for LAD antibodies remains to be determined.

PMID- 8136318
TI  - The change of melanocyte cytotoxicity after systemic steroid treatment in
      vitiligo patients.
AB  - Although there is evidence of a strong association between antimelanocyte
      autoantibodies and vitiligo, the etiology of vitiligo is still unclear. To
      elucidate the biological significance of antimelanocyte autoantibodies in
      vitiligo, we measured the percent cytotoxicity of melanocyte mediated by
      autoantibody and complement in normal controls (n = 31) and in the patients with
      active, progressive vitiligo (n = 37). Significant differences in percent
      cytotoxicity of melanocyte were seen between the control and vitiligo groups (P =
      0.0001). There were no significant differences in the percent cytotoxicity of
      melanocyte between the patients (n = 24) with more than 1 year duration and those
      (n = 13) with less than 1 year duration. The change of percent cytotoxicity
      between pre- and post-treatment groups (n = 29) with systemic steroid showed
      significant differences (P = 0.0243). These findings support the hypothesis that
      a decrease in the antibody-mediated cytotoxicity against melanocytes may play a
      role in the improvement of vitiliginous lesions after systemic steroid treatment.

PMID- 8136319
TI  - Testosterone metabolism by cultured human beard outer root sheath cells in
      comparison with epidermal keratinocytes.
AB  - In order to elucidate the mechanism of action of androgen in human hair
      follicles, we studied testosterone metabolism by cultured beard outer root sheath
      cells in comparison with that of epidermal keratinocytes. When cells were
      incubated as a monolayer in serum-free keratinocyte growth medium with
      physiological concentrations (25 nM) of [3H]testosterone, the major metabolite
      was androstenedione in either type of cells. Small amounts of androstanedione,
      dihydrotestosterone and androsterone were also formed. The ratio of apparent 5
      alpha-reductase to 17 beta-hydroxy-steroid dehydrogenase activities ranged from
      0.11 to 0.81 and did not differ between these two kinds of cells. After these
      cells were cultured in the presence of 10% fetal calf serum for 10 days, the
      activities of both metabolic pathways markedly increased without significant
      changes of the ratio of activities of these two enzymes. Thus, testosterone was
      rather converted to weak androgens even in beard outer root sheath cells under
      the experimental conditions.

PMID- 8136320
TI  - Localization of annexins in normal and diseased human skin.
AB  - Annexins (AX) or lipocortins are a family of calcium and phospholipid binding
      proteins that have been implicated to play a role in the regulation of
      inflammation and cellular differentiation. To investigate a potential role of AX
      in skin disorders we studied the distribution of six different AX in normal human
      skin (NHS) and several inflammatory and hyperproliferative skin diseases. A
      distinct staining pattern could only be shown for AX-1 and AX-2. In NHS AX-1
      antibody (Ab) displayed a very strong reactivity with eccrine sweat ducts. In the
      diseases investigated we found a highly increased expression of AX-1 in
      keratinocytes (KCs) in the vicinity of inflammatory processes such as psoriasis.
      Furthermore, the AX-1 expression was increased in differentiated squamous cell
      carcinoma (SCC) whereas undifferentiated SCC and basal cell carcinoma were
      negative. AX-3, -4, -5, and -6 showed no distinctive expression pattern. Our data
      demonstrate an abnormal distribution of AX-1 in association with proliferating
      KCs under inflammatory and neoplastic conditions. Its pattern of reactivity shows
      similarities to the known distribution of the EGF-receptor kinase, which has been
      demonstrated to phosphorylate AX-1 with high activity in various cellular
      systems. These results support the concept that the appearance of AX-1 is linked
      to a certain level of KC differentiation.

PMID- 8136321
TI  - A combined therapeutic modality with hyperthermia and locally administered rIFN
      beta inhibited the growth of B16 melanoma in association with the modulation of
      cellular infiltrates.
AB  - Murine B16-F10 melanoma was treated with local microwave hyperthermia, local
      injection of murine recombinant interferon-beta (rIFN-beta) or a combination of
      both in order to investigate the augmentation of anti-proliferative effects with
      this combination treatment. Concerning the local modulation of immunological
      reactions of the host, local hyperthermia at 43 degrees C for 15 min on murine
      melanoma caused remarkable infiltration of natural killer cells and local
      injection of rIFN-beta led to considerable infiltration of T cells. When these
      two modalities were combined, the infiltration of NK cells completely disappeared
      and, instead, remarkable augmentation of T cell infiltration occurred.
      Synergistic suppressive effects on melanoma growth with occasional scar formation
      were seen with this combined modality. These results indicate that local
      hyperthermia with a combination of rIFN-beta modulates local immune reactions of
      the host, and probably this immune reaction is partly involved in the course of
      the suppression of tumor growth.

PMID- 8136322
TI  - Interaction of Staphylococcus aureus cells and silk threads in vitro and in mouse
      skin.
AB  - Staphylococcus aureus cell suspension was epicutaneously inoculated on the back
      skin of cyclophosphamide-treated mice with silk stitches and these sites were
      occluded. Biopsy specimens were taken from three mice at 1, 3, 6, 12, 24, 48, and
      72 h after inoculation and were examined by electron microscopy. Fibril-like
      structures (glycocalyx) were seen around the S. aureus cells at 1 h. At 3 h, they
      had extended towards the silk threads. There were microcolonies on the surfaces
      of the silk threads and at 12 h the S. aureus cells were enclosed in membrane
      like structures. The electron density of the membrane-like structures increased
      over time. After ruthenium red staining, the membrane-like structures and the
      fibril-like structures were stained positive, suggesting that these structures
      contain polysaccharide components. With a combination chemotherapy using
      clarithromycin and ofloxacin, S. aureus cells in the membrane-like structures
      were degenerated, whereas the use of clarithromycin or ofloxacin alone had little
      effect. Chlorhexidin gluconate and povidone iodine were effective if they were
      able to reach the biofilm. The fibril-like structures appeared in vitro only in
      the presence of silk threads, and were enhanced by the presence of mouse plasma.
      These structures did not form with formaldehyde-killed S. aureus cells. Thus, S.
      aureus cells may interact with foreign bodies to form biofilms, thereby evading
      the effect of antibacterial agents.

PMID- 8136323
TI  - Presence of the factor that inhibits collagen synthesis and stimulates cell
      proliferation in developing embryonic chick skin extracts.
AB  - The effects were studied of the extracts prepared from 10- and 18-day developing
      chick skins on collagen synthesis and proliferation of the monolayered
      fibroblasts established from 10-day skin. Cell proliferation was stimulated by
      both 10- and 18-day skin extracts at the concentration of 3.5 micrograms/ml.
      Collagen synthesis was suppressed by the treatment of extracts prepared from both
      10- and 18-day skins at the concentration of 3.5 micrograms/ml, to a greater
      extent in 18-day extract. The results indicate that skin extracts possess factors
      exhibiting both a stimulating effect on cell proliferation and an inhibitory
      effect on collagen synthesis.

PMID- 8136324
TI  - Display and interpretation of solvent electron density distributions in insulin
      crystals.
AB  - In macromolecular crystallography, three-dimensional contour surfaces are useful
      for interactive computer graphics displays of the protein electron density but
      are less effective for presenting static images of large volumes of solvent
      density. A raster-based computer graphics program which displays depth-cued
      projections of continuous density distributions has been developed to analyze the
      distribution of solvent atoms in macromolecular crystals. Maps of the water
      distribution in the cubic insulin crystal show some well-ordered waters, which
      are bound to surrounding protein atoms by multiple hydrogen bonds, and an ill
      defined solvent structure at a greater distance from the protein surface.
      Molecular dynamics calculations were used to assist in the interpretation of the
      time-varying solvent structure within two enclosed cavities in the crystal. Two
      water molecules that ligate a sodium ion were almost immobile during the
      stimulation but the majority of water molecules were found to move rapidly
      between the density maxima identified from the crystallographic refinement.

PMID- 8136325
TI  - Protein three-dimensional structure generation with an empirical hydrophobic
      penalty function.
AB  - Given current computational environments, it is worthwhile to establish amino
      acid residue-level functions which approximate protein folds quite well. Such
      functions must be the interim steps toward protein three-dimensional structure
      prediction. I have shown that an empirical hydrophobic penalty function of
      protein, derived from the number of residues in a sphere around each residue,
      could be utilized to distinguish the correctly folded structure from the
      incorrect ones. In order to assess the predictive power of the penalty function,
      I have generated conformations by randomly changing main chain dihedral angles,
      and applied the penalty function to them. If only a local region was allowed to
      change its conformation, native-like structures could be generated within a
      reasonable computational time. In global simulations, however, a considerable
      number of nonnative conformations, which gave as small a penalty value as that of
      the native protein, were found. Although some of the conformations were compact
      and globular, they were quite different from the native structure in that they
      lacked most of the secondary structures. This result shows that the penalty
      function alone cannot define the native structure, and that substructure
      information may help the penalty function to reach the correctly folded
      structure.

PMID- 8136327
TI  - A technique for identifying atoms from a screen image.
AB  - Improving the interfaces in molecular graphics applications, making them more
      natural and easy to use, is an important task, given the current complexity of
      the displayed objects and of modeling operations. Clicking near an atom center is
      the usual method of atom selection. However, this method has certain
      disadvantages when working with images composed of different atomic
      representations such as sticks, CPK, or dotted surfaces. We propose another
      technique allowing the user to obtain the correct answer when he or she clicks on
      any element of the atom image.

PMID- 8136326
TI  - A 3D model of the peripheral benzodiazepine receptor and its implication in intra
      mitochondrial cholesterol transport.
AB  - A three-dimensional (3D) model of the peripheral benzodiazepine receptor (PBR)
      has been built using molecular dynamics simulations. The transmembrane domain of
      the receptor has been modeled as five alpha-helices, which are not long enough to
      cross the entire bilayer membrane but correspond approximately to only one
      phospholipid layer. The receptor model has also been tested as a cholesterol
      carrier, and molecular dynamics simulations have shown that it could indeed
      accommodate a cholesterol molecule within the five helices. All three known PBR
      sequences have been modeled, and no significant difference has been found between
      them.

PMID- 8136328
TI  - Meeting on binding sites: characterizing and satisfying steric and chemical
      restraints. University of York, 28-30 March 1993.

PMID- 8136330
TI  - The management of patients with a cleft lip and palate deformity.

PMID- 8136329
TI  - Twelfth annual conference of the Molecular Graphics Society. Interlaken, 7-11
      June 1993.

PMID- 8136331
TI  - The measurement of injury severity.
AB  - Severity of injury can now be measured objectively and in a manner relevant to
      everyday practice. A variety of scales/scores are available which are based
      either on anatomical or physiological parameters or a combination of these. ASCOT
      methodology represents the most recent major contribution in this area, and
      follows AIS and TRISS as an established and reliable means of assessing trauma
      patients, particularly in relation to survival. These methods have clinical
      application in terms of triage, directing clinical management, assessing
      prognosis, assessing cost of management and for measuring outcome. The
      development of these scoring methods is outlined in this paper.

PMID- 8136332
TI  - Aetiology of maxillofacial fracture.
AB  - The aetiological factors associated with maxillofacial fractures, and the trends
      in these factors over a 13 year period are reported. The First Department of Oral
      and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental
      University, managed 695 patients with maxillofacial fractures between 1977 and
      1989. The male to female ratio was 3.2:1 and the majority of patients were aged
      between 10 and 30 years old. Road traffic accidents and accidental falls were the
      main causes of fractures throughout the 13 year study period. Mandibular
      fractures occurred in 477 patients (68.6%). A high percentage of patients were
      treated by closed reduction and maxillo-mandibular fixation, or occlusal
      splinting.

PMID- 8136333
TI  - The percutaneous dilatational subcricoid tracheostomy.
AB  - Tracheostomy is frequently required during maxillofacial procedures. The
      percutaneous technique is described and advocated as a rapid easily mastered
      procedure, although there is a definite learning curve and it is not without a
      potential for complications.

PMID- 8136334
TI  - The medical management of masseteric hypertrophy with botulinum toxin type A.
AB  - We describe the successful outpatient medical treatment of a patient with
      bilateral masseteric hypertrophy using botulinum toxin type A in a double-blind
      placebo controlled study. No significant side-effects occurred, and benefit has
      so far lasted for 6 months.

PMID- 8136335
TI  - Botulinum toxin treatment of bilateral masseteric hypertrophy.
AB  - Botulinum toxin is a new and innovative method of treating bilateral masseteric
      hypertrophy which offers many advantages over conventional surgical treatment.
      Experience gained through the successful use of this drug when given as an
      intramuscular injection is reported. No significant side-effects have occurred
      and this technique is recommended for the routine treatment of masseteric
      hypertrophy.

PMID- 8136336
TI  - Complications of tracheostomy in major head and neck cancer surgery; a
      retrospective study of 60 consecutive cases.
AB  - Employment of tracheostomy in head and neck cancer surgery remains controversial.
      This study details those cases in which the life-saving potential of tracheostomy
      placement was considered to outweigh the observed disadvantages. Sixty
      consecutive cases of tracheostomy in head and neck cancer patients were assessed
      and revealed a relatively low complication rate (11% of cases). Chest infection
      was the commonest problem encountered, although none were life threatening and
      all responded to treatment. Surgical and medical management aimed at reducing
      tracheostomy complications is discussed.

PMID- 8136337
TI  - Informed consent in oral and maxillofacial surgery: a study of the value of
      written warnings.
AB  - OBJECTIVE: To determine if written preoperative warnings about risks and outcomes
      of surgery improves patients' recall and recognition of these warnings
      postoperatively compared to traditional verbal warnings and to determine if the
      timing of these warnings is significant. DESIGN: Prospective study of patients
      given written warnings compared to a control group of patients warned in the
      traditional verbal way. SETTING: Oral and Maxillofacial unit of a District
      General Hospital. SUBJECTS: Patients undergoing removal of third molars under
      general anaesthesia. MAIN OUTCOME MEASURES: Patients' recall and recognition of
      warnings about pain, swelling, trismus and lingual and labial dysaesthesias given
      before surgery for removal of third molars. RESULTS: Written information
      significantly improves patients recall and recognition of important warnings such
      as the risk of dysaesthesia of the tongue (p < 0.001) and lip (p < 0.01) when
      compared with just verbal warnings. It seems to make no difference if this
      information is given to the patient a week before on a preadmission clinic or on
      admission. CONCLUSIONS: Written preoperative information about routine operations
      would improve the quality of the informed consent process.

PMID- 8136338
TI  - Tongue piercing (oral body art).
AB  - Oral body art is a relatively recent fashion in the West where jewelry is
      inserted in the oral soft tissues. A patient who had tongue-piercing is
      presented, and the subject of oral piercing reviewed.

PMID- 8136340
TI  - The Kirschner wire guide.
AB  - The Kirschner wire guide is a useful means of introducing K-wires into the facial
      skeleton. It can be easily constructed in the maxillofacial laboratory and its
      use allows accurate positioning of K-wires, especially in fractures of the
      zygomatic complex.

PMID- 8136339
TI  - Primary malignant melanoma of the oral cavity--its histological classification
      and treatment.
AB  - In contrast to Caucasians, the Japanese population has a relatively high
      incidence of malignant melanoma in the oral cavity, but its classification and
      treatment has not been established up to now. We present here the detailed
      clinical and histological features of 14 cases of oral melanoma. In 13 of the 14
      patients, the lesions exhibited three phases: a nodular phase consisting of
      spindle-shaped or epithelioid tumor cells in the submucosa, a pigmented plaque
      phase consisting of preinvasive tumor cell nests in the lower epithelial layers,
      and a macular phase consisting of proliferation of dendritic melanocytes without
      apparent atypia or simple hyperpigmentation in the basal cell layer. The
      macroscopic and microscopic findings of 13 melanomas corresponded to those of
      acral lentiginous melanoma of the skin, while the one lesion showing no radial
      growth phase was classified as nodular melanoma. We devised a new treatment plan
      for oral melanoma in 1980, which includes surgical excision via an intraoral
      approach, therapeutic neck dissection, and adjuvant immunochemotherapy. Out of 11
      patients treated in this manner, nine had a good outcome without major cosmetic
      and functional morbidity. This suggests that the prognosis of oral melanoma is
      not so poor as reported previously if adequate therapy is provided.

PMID- 8136341
TI  - A technique to stabilize the radius after harvesting osteocutaneous flaps.

PMID- 8136342
TI  - A simple modification to titanium miniplates.

PMID- 8136343
TI  - Closure of radial forearm free flap defect using full-thickness skin from the
      anterior abdominal wall.
AB  - One of the major problems associated with the radial forearm free flap is donor
      site morbidity. Traditionally the defect is repaired using a split-thickness skin
      graft which gives poor coverage of the underlying structures, is unsightly, and
      in the long term may result in marked scarring. There is also morbidity
      associated with the skin graft donor site. We describe an alternative technique
      for closure of the donor site using full-thickness skin from the anterior
      abdominal wall. We believe this technique reduces not only donor site morbidity
      but also morbidity at the graft site.

PMID- 8136344
TI  - The 3-dimensional stability of maxillary osteotomies in cleft palate patients
      with residual alveolar clefts.
AB  - OBJECTIVES: To evaluate the stability of maxillary osteotomies in cleft palate
      patients using miniplate fixation. DESIGN: A prospective clinical study.
      SUBJECTS: 46 consecutive cleft palate patients with residual alveolar clefts and
      maxillary hypoplasia in one or more dimensions. These patients underwent
      standardised maxillary osteotomies and simultaneous bone grafting of the alveolar
      cleft over 44 months during 1988-1992. Titanium mini-plate fixation was used for
      the maxilla in all patients. Follow-up ranged from 6 to 51 months with a mean of
      28 months. MAIN OUTCOME MEASURES: The 3-dimensional stability of maxillary
      osteotomies in cleft palate patients in the long term. RESULTS: In the unilateral
      clefts, relapse in the horizontal plane was 22% and in the vertical plane 22.5%;
      in bilateral clefts, the relapse was 17.5% and 7% respectively, with no
      statistically significant difference between the two groups. Longitudinal
      analysis of the repositioned maxilla over a 3-year period showed that most of the
      relapse occurred in the first 6 months and stabilised at 2 years postoperatively.
      Relapse in the transverse plane, based on analysis of the study models of 26
      cases, ranged from 13.4% to 33.6%. A clockwise rotational relapse of the maxilla
      was noted in bilateral cases. Postoperative orthodontics compensated for the
      horizontal relapse by increasing incisor proclination to maintain positive
      overjet. There was no significant difference between the relapse of bimaxillary
      cases and that of maxillary osteotomies alone. CONCLUSION: The long-term 3
      dimensional surgical stability, using miniplate fixation, has decreased the
      relapse of cleft maxillary osteotomies with simultaneous alveolar bone grafting
      to a level comparable to that of maxillary osteotomies in non-cleft patients.

PMID- 8136345
TI  - The future training of maxillofacial surgeons.

PMID- 8136346
TI  - Whither the treatment for the TMJ?

PMID- 8136347
TI  - Trapping kinetics in mutants of the photosynthetic purple bacterium Rhodobacter
      sphaeroides: influence of the charge separation rate and consequences for the
      rate-limiting step in the light-harvesting process.
AB  - The primary light-harvesting processes, energy transfer in the light-harvesting
      antenna, and trapping of the excited states by reaction centers were studied in
      several mutant strains of the photosynthetic purple bacterium Rhodobacter
      sphaeroides. The mutants had reaction centers in which the rates of electron
      transfer were modified by site-directed mutations at the M210 position. Low
      intensity pump-probe laser spectroscopy was used to monitor the absorbance
      transients in the Qy region of the antenna pigments, and it was found that
      despite a wide variation in charge separation rates within the RC, produced by
      the alterations at Tyr M210, there was relatively little corresponding variation
      in the overall trapping rate. These effects of the mutations on the trapping
      kinetics demonstrate that the rate-limiting step of the overall light-harvesting
      process is the transfer of the excitations from the antenna to the reaction
      center.

PMID- 8136348
TI  - Potential active-site base of thioredoxin reductase from Escherichia coli:
      examination of histidine245 and aspartate139 by site-directed mutagenesis.
AB  - It has been proposed that an acid-base catalyst facilitates the reduction of
      thioredoxin by thioredoxin reductase from Escherichia coli [O'Donnell, M. E., &
      Williams, C. H. Jr. (1983) J. Biol. Chem. 252, 13795-13805]. The X-ray crystal
      structure reveals two groups which could potentially fulfill this role: His245
      and Asp139. Using site-directed mutagenesis, His245 was changed to asparagine
      (H245N) and alanine (H245A) and Asp139 was changed to glutamate (D139E),
      asparagine (D139N), and leucine (D139L). Steady-state kinetic analysis of the
      His245 mutants gave turnover numbers and Km values similar to those of wild-type
      thioredoxin reductase. All three Asp139 mutants were altered in their overall
      kinetic properties: D139E had 38% of wild-type activity, D139N had 1.5%, and
      D139L had no measureable activity. Rate constants for the NADPH to 3
      acetylpyridine adenine dinucleotide phosphate transhydrogenase activity were
      similar for all of the Asp139 and His245 mutants and wild-type thioredoxin
      reductase. Stopped-flow kinetic measurements of the reductase half-reaction of
      H245A and H245N gave rate constants that were up to 2-fold faster than those
      found for wild-type thioredoxin reductase, while all of the Asp139 mutants had
      rate constants comparable to those of wild-type. To further examine the causes of
      the low overall activity of D139N, the oxidative half-reaction was measured. The
      reoxidation of reduced D139N mixed with oxidized thioredoxin occurred at a very
      slow rate constant of 0.23 s-1-about 1% that of wild-type enzyme. We suggest that
      Asp139 is the active-site acid catalyst which functions to protonate the thiolate
      anion of reduced thioredoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136349
TI  - Optical, EPR, and 1H NMR spectroscopy of serine-ligated [2Fe-2S] ferredoxins
      produced by site-directed mutagenesis of cysteine residues in recombinant
      Anabaena 7120 vegetative ferredoxin.
AB  - Anabaena 7120 vegetative ferredoxin is a plant-type [2Fe-2S] ferredoxin that
      contains only four cysteine residues. The four cysteines (Cys41, Cys46, Cys49,
      and Cys79), which ligate the iron-sulfur cluster, were mutated individually to
      serine. The wild-type and mutant apoprotein genes were overexpressed in
      Escherichia coli, and the iron-sulfur cluster was assembled in vitro by adding
      iron and sulfide. UV-vis, EPR, and 1H NMR spectra were recorded on the wild-type
      ferredoxin and mutants. The optical spectra of all mutant proteins, in the
      oxidized state, differed from that of wild-type ferredoxin. Three of the mutant
      proteins (Cys46Ser, Cys49Ser, and Cys79Ser) exhibited a rhombic EPR spectrum in
      the reduced state, but one (Cys41Ser) showed a near-axial EPR spectrum. The 1H
      NMR spectra of each of the four oxidized mutants contained a group of broad,
      hyperfine-shifted peaks between 20 and 30 ppm with anti-Curie temperature
      dependence. The pattern of these peaks was different for each mutant, and all
      were distinct from that of the wild-type ferredoxin. Because of problems with
      protein stability, it was possible to obtain NMR spectra of only two of the
      mutants when reduced. The downfield hyperfine 1H NMR spectrum of the reduced
      Cys46Ser mutant resembled that of wild-type ferredoxin, but that of the Cys49Ser
      mutant did not. The hyperfine-shifted resonances of the 1H NMR spectrum of the
      reduced Cys46Ser mutant were assigned on the basis of results from temperature
      dependence studies, measurements of nuclear Overhauser effect, and 1H NMR spectra
      of the mutant labeled with [beta-2H]cysteine. Four hyperfine-shifted peaks of
      reduced Cys49Ser at 298 K were observed at 173, 120, 32, and 18 ppm. These peaks
      exhibited Curie-type temperature dependence and were tentatively assigned to
      protons from residues coordinated to Fe(III). The reduced Cys49Ser mutant showed
      an additional 1H NMR peak at -15 ppm (at 298 K) with Curie-type temperature
      dependence whose origin is unknown at present. [2Fe-2S] clusters can be placed
      into three different classifications according to their EPR lines shapes, NMR
      spectra, and reduction potentials: plant type, vertebrate type, and Rieske type.
      The EPR and NMR results obtained here reveal that mutant Cys46Ser has a "plant
      type" cluster but that mutant Cys49Ser has a "vertebrate-type" cluster. Cysteine
      to serine mutations have been employed in the past to probe whether particular
      cysteine residues participate as iron-sulfur ligands.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8136350
TI  - Fucoxanthin-chlorophyll a/c light-harvesting complexes of Laminaria saccharina:
      partial amino acid sequences and arrangement in thylakoid membranes.
AB  - The N-terminus of the major polypeptide component of the light-harvesting complex
      (LHC) from the brown alga Laminaria saccharina is blocked. Two partial sequences,
      one near the N-terminus and the other near the C-terminus, have been obtained by
      chemical cleavage with acetic acid and N-chlorosuccinimide. Four peptides were
      separated after trypsin digestion of the thylakoid membranes. One fragment is not
      phosphorylated, is not blocked, and has been sequenced. Purification on a
      reversed-phase column showed two forms of the LHC protein: the more hydrophobic
      form appears to be bound to photosystem I. These results are compared with LHC
      from other Chromophytes and the CAB family of green plants.

PMID- 8136351
TI  - EPR and electron nuclear double resonance (ENDOR) studies show nitrite binding to
      the type 2 copper centers of the dissimilatory nitrite reductase of Alcaligenes
      xylosoxidans (NCIMB 11015).
AB  - EPR and 1H, 14,15N ENDOR spectra are described for the type 1 and type 2 Cu(II)
      centers of dissimilatory nitrite reductase (NiR) from Alcaligenes xylosoxidans.
      The study was carried out on preparations of NiR containing both type 1 and type
      2 Cu sites, and also on preparations of lower activity which contained
      essentially only type 1 Cu centers. This has enabled ENDOR studies of type 1 and
      type 2 sites to be carried out largely independently of each other, by
      appropriate choice of the excitation field. Spectra were recorded both in the
      absence and presence of nitrite, allowing a clear determination of which of the
      two types of Cu center constitutes the substrate binding site. The EPR results
      show large changes in the type 2 site gparallel (which decreases by 0.065) and
      CuAparallel (which increases by 2.0 mT) while the type 1 site EPR is not
      affected. In addition, both 1H and 14N ENDOR of the type 2 Cu site undergo
      considerable changes on addition of nitrite whereas the type 1 Cu site ENDOR is
      unaffected. Our results clearly demonstrate that nitrite binds to the type 2
      copper and that this process significantly perturbs the ligation of this copper
      by the protein histidine residues. No 15N ENDOR resonances were observed from 15N
      nitrite. The accessibility of the copper sites to solvent has been studied using
      2H2O. The results indicate that nitrite binds to the type 2 Cu by displacing a
      proton, probably on a water molecule bound to the copper atom.

PMID- 8136353
TI  - Time-resolved fluorescence and absorption spectroscopy of photosystem I.
AB  - Picosecond fluorescence and femtosecond transient absorption spectroscopy have
      been used to investigate the primary energy transfer and trapping processes in a
      photosystem II deletion mutant from the cyanobacterium Synechocystis sp. PCC
      6803, which contains active photosystem I reaction centers with approximately 100
      chlorophylls per P700. In all experiments, low levels of excitation were used
      which avoid annihilation processes. Following 590-nm excitation, at room
      temperature, spectral equilibration is observed in both fluorescence and
      absorption measurements and is characterized by a time constant of 4-6 ps. The
      shape of the spectra associated with the equilibration process indicates that
      long wavelength pigments (pigments with absorption maxima at longer wavelength
      than that of the primary electron donor, P700) are present and functional at
      physiological temperatures in this preparation. The overall decay of excitations
      in the antenna is characterized by a time constant of 24-28 ps, in both
      fluorescence and absorption measurements. The 24-28-ps process results in the
      appearance of absorption changes associated with only P700+ formation. Absorption
      changes associated with the reduction of the primary electron acceptor were not
      resolved under the experimental conditions used here.

PMID- 8136352
TI  - Complete identification of C = O stretching vibrational bands of protonated
      aspartic acid residues in the difference infrared spectra of M and N
      intermediates versus bacteriorhodopsin.
AB  - Fourier transform infrared difference spectra were obtained for the M and N
      intermediates versus light-adapted bacteriorhodopsin (BR) with site-directed
      mutant proteins in which aspartic acid residues at positions 96 and 115 were
      replaced by asparagine. The positive and negative bands at 1740 and 1732 cm-1 in
      the M/BR spectrum are shown to be the superposition of bands due to C = O
      stretching vibrations of Asp-96 and Asp-115 (a positive band at 1736 cm-1 and a
      negative band at 1742 cm-1 of Asp-96, and a positive band at 1742 cm-1 and a
      negative band at 1734 cm-1 of Asp-115). The positive band at 1738 cm-1 and the
      negative band at 1734 cm-1 in the N/BR spectrum are attributed to Asp-115. On the
      basis of these results, Asp-115 is protonated in M and N as well as in the ground
      state. On the other hand, no bands corresponding to Asp-212 were found in the
      region of protonated carboxylic acid vibration, indicating that Asp-212 remains
      unprotonated in M and N. The frequencies of the C = O stretching modes of
      protonated Asp-96 and Asp-115 change in the opposite direction in the BR-to-M
      conversion relative to the shifts in the BR-to-L conversion, indicating different
      environmental changes for these residues in L and M.

PMID- 8136354
TI  - Observation of the reduction and reoxidation of the primary electron acceptor in
      photosystem I.
AB  - Femtosecond transient absorption spectroscopy has been used to investigate the
      primary charge separation in a photosystem II deletion mutant from the
      cyanobacterium Synechocystis sp. PCC 6803. These cells contain only the
      photosystem I reaction center and have a pigment content of approximately 100
      chlorophylls per P700. Utilizing relatively high excitation intensities, the
      difference spectrum for the reduction of primary electron acceptor [(A0(-)-A0)
      difference spectrum] was obtained from experiments performed under both reducing
      and oxidizing conditions. Both approaches yield very similar results with the
      (A0(-)-A0) difference spectrum displaying a maximum bleaching at 687 nm. The
      shape of the difference spectrum suggests that the primary electron acceptor in
      photosystem I may be a chlorophyll a molecule. The observed rate of primary
      radical pair formation depends on the overall rate of decay of excitations in the
      antenna; the radical pair state forms as the antenna decays. The decay of the
      primary radical pair state is characterized by a 21-ps time constant. Under
      conditions that avoid annihilation effects, the mean lifetime for excitations in
      the antenna is 28 ps [Hastings, G., Kleinherenbrink, F.A.M., Lin, S., &
      Blankenship, R.E. (1994) Biochemistry (preceding paper in this issue)]. This
      indicates that the reduced acceptor decays faster than it forms. Therefore, only
      a low concentration of the reduced acceptor will accumulate under most
      conditions.

PMID- 8136355
TI  - Interaction of the HIV-1 fusion peptide with phospholipid vesicles: different
      structural requirements for fusion and leakage.
AB  - This paper presents a study on the membrane fusion activity of a 23-residue
      synthetic peptide, representing the N-terminus of gp41 of the human
      immunodeficiency virus type I (HIV-1; LAV1a strain), in a model system involving
      large unilamellar vesicles (LUV) composed of the negatively charged 1-palmitoyl-2
      oleoylphosphatidylglycerol (POPG). The peptide (HIVarg) induced fusion of POPG
      LUV as evidenced by (i) mixing of membrane lipids, (ii) mixing of aqueous vesicle
      contents, and (iii) an irreversible increase in vesicle size. Fusion could be
      induced only in the presence of millimolar concentrations of Ca2+ or Mg2+, needed
      for induction of vesicle aggregation; the divalent cations by themselves did not
      induce any fusion. The rate constant of the fusion reaction, as determined by
      simulation of the process according to a kinetic model, increased dramatically
      with the peptide-to-lipid molar ratio, indicating that the peptide was the
      mediator of the process. In the absence of divalent cations, the HIVarg peptide
      induced leakage of small molecules due to formation of pores in the membrane of
      single vesicles. Final extents and kinetics of this leakage process could be
      simulated adequately by model calculations for peptide-to-lipid ratios ranging
      from 1:25 to 1:750. Experiments, in which the order of peptide and Ca2+ addition
      to the vesicles was varied, indicated that the peptide is likely to adopt two
      different structures, one in the absence of Ca2+, primarily supporting leakage by
      formation of pores in separate vesicles, and one in the presence of Ca2+,
      primarily supporting fusion. Once a final structure had been established, it
      persisted even upon addition or removal of Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136356
TI  - Caldesmon, N-terminal yeast actin mutants, and the regulation of actomyosin
      interactions.
AB  - N-Terminal yeast actin mutants were used to assess the role of N-terminal acidic
      residues in the interactions of caldesmon with actin. The yeast actins differed
      only in their N-terminal charge: wild type, two negative charges; 4Ac, four
      negative charges; DNEQ, neutral charge; delta DSE, one positive charge. Caldesmon
      inhibition of actomyosin subfragment 1 ATPase was affected by alterations in the
      N-terminus of actin. This inhibition was similar for skeletal muscle alpha-actin
      and the yeast 4Ac and wild-type actins (80%), but much smaller for the neutral
      and deletion mutants (15%). However, cosedimentation experiments revealed similar
      binding of caldesmon to polymerized rabbit skeletal muscle alpha-actin and each
      yeast actin. This result shows that the N-terminal acidic residues of actin are
      not required for the binding of caldesmon to F-actin. Caldesmon-actin
      interactions were also examined by monitoring the polymerization of G-actin
      induced by caldesmon. Although the final extent of polymerization was similar for
      all actins tested, the rates of polymerization differed. Skeletal muscle and 4Ac
      actins had similar rates of polymerization, and the wild-type actin polymerized
      at a slower rate. The neutral and deletion mutants had even slower rates of
      polymerization by caldesmon. The slow polymerization of DNEQ G-actin was traced
      to a greatly reduced binding of caldesmon to this mutant G-actin when compared to
      wild-type and alpha-actin. MgCl2-induced actin polymerization proceeded at
      identical rates for all actins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136357
TI  - Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium
      binding motifs and gene localization to human chromosome 5.
AB  - Calnexin is a 90-kDa integral membrane protein of the endoplasmic reticulum (ER).
      Calnexin binds Ca2+ and may function as a chaperone in the transition of proteins
      from the ER to the outer cellular membrane. We have purified human calnexin in
      association with the human interferon-gamma receptor and cloned calnexin cDNA
      from placenta. Fragments of calnexin have been prepared as glutathione S
      transferase fusion proteins and analyzed for their abilities to bind 45Ca2+ and
      ruthenium red. A subdomain containing four internal repeats binds Ca2+ with the
      highest affinity. This sequence is highly conserved when compared to calreticulin
      (a luminal ER protein), an Onchocerca surface antigen, and yeast and plant
      calnexin homologues. Consequently, this sequence represents a conserved motif for
      the high-affinity binding of Ca2+, which is clearly distinct from the "E-F hand"
      motif. An adjacent subdomain, also highly conserved and containing four internal
      repeats, fails to bind Ca2+. The carboxyl-terminal, cytosolic domain is highly
      charged and binds Ca2+ with moderate affinity, presumably by electrostatic
      interactions. The calnexin amino-terminal domain (residues 1-253) also binds
      Ca2+, in contrast to the amino-terminal domain of calreticulin, which is
      relatively less acidic. We have also determined the cDNA sequences of mouse and
      rat calnexins. Comparison of the known mammalian calnexin sequences reveals very
      high conservation of sequence identity (93-98%), suggesting that calnexin
      performs important cellular functions. The gene for human calnexin is located on
      the distal end of the long arm of human chromosome 5, at 5q35.

PMID- 8136358
TI  - Role of glutamine-61 in the hydrolysis of GTP by p21H-ras: an experimental and
      theoretical study.
AB  - The active GTP-bound form of p21ras is converted to the biologically inactive GDP
      bound form by enzymatic hydrolysis and this function serves to regulate the wild
      type ras protein. The side chain of the amino acid at position 61 may play a key
      role in this hydrolysis of GTP by p21. Experimental studies that define
      properties of the Q61E mutant of p21H-ras are presented along with supporting
      molecular dynamics simulations. We find that under saturating concentrations of
      GTP the Q61E mutant of p21H-ras has a 20-fold greater rate of intrinsic
      hydrolysis (kcat = 0.57 min-1) than the wild type. The affinity of the Q61E
      variant for GTP (Kd = 115 microM) is much lower than that of the wild type.
      GTPase activating protein does not activate the variant. From molecular dynamics
      simulations, we find that both the wild type and Q61E mutant have the residue 61
      side chain in transient contact with a water molecule that is well-positioned for
      hydrolytic attack on the gamma phosphate. Thr-35 also is found to form a
      transient hydrogen bond with this critical water. These elements may define the
      catalytic complex for hydrolysis of the GTP [Pai et al. (1990) EMBO J. 9, 2351].
      Similarly, the G12P mutant, which also has an intrinsic hydrolysis rate similar
      to the wild type, is found to form the same complex in simulation. In contrast,
      molecular dynamics analysis of the mutants G12R, G12V, and Q61L, which have much
      lower intrinsic rates than the wild-type p21, do not show this complex.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8136359
TI  - Hydration and localization of diacylglycerol in the insect lipoprotein
      lipophorin. A 13C-NMR study.
AB  - In order to probe the organization of diacylglycerol (DG) in lipophorin, 13C
      enriched lipophorin was prepared for NMR investigations. We obtained 13C-enriched
      lipophorin labeled exclusively in DG by feeding insects tobacco leaves coated
      with [1-13C]palmitic acid or [1-13C]oleic acid. Lipophorins enriched up to 5%
      with a [13C]fatty acid were obtained by this procedure. NMR studies of the
      isolated lipophorin DG showed that palmitic acid accumulates almost entirely (>
      90%) in the sn-1 position. Oleic acid was found equally distributed between the
      sn-1 and sn-2 positions, yielding a DG enriched equally at both positions. The
      13C-NMR spectra of both [13C]palmitate- and [13C]oleate-enriched lipophorins
      showed that DG had one narrow carbonyl resonance indicative of rapid motion. A
      comparative analysis of the 13C carbonyl chemical shift data for DG in organic
      solvents, aqueous solutions, and dispersions with the DG carbonyl chemical shift
      of native lipophorin enriched in [13C]palmitate or [13C]oleate shows a high
      degree of water exclusion from the DG carbonyls in lipophorin. This result is
      consistent with the existence of a lipophorin lipid core containing most of the
      lipophorin DG. This study represents the first attempt to elucidate the
      organization of DG in lipophorin. The possibility of obtaining [13C]DG-enriched
      lipophorins, selectively enriched in one or both acyl chains of DG, should
      provide a powerful tool for further analysis of the organization and the dynamic
      properties of DG in native lipoproteins.

PMID- 8136360
TI  - Exogenous acetate reconstitutes the enzymatic activity of trypsin Asp189Ser.
AB  - The specificity of trypsin for Arg- and Lys-containing substrates depends upon
      the presence of Asp189 at the base of the primary binding pocket. The crystal
      structure of anionic rat trypsin D189S complexed with BPTI reveals that removal
      of the aspartate side chain permits the binding of a well-ordered acetate ion in
      a similar position. The acetate makes polar interactions with Gly226, Tyr228, and
      several water molecules and is further accommodated by rotation of the Ser189
      side chain out of the binding pocket. The carboxylate group of the acetate anion
      is oriented toward the substrate in a manner similar to that of Asp189 and Asp226
      in wild-type trypsin and trypsin D189G/G226D. Evaluation of kinetic parameters
      for amide substrate cleavage by trypsin D189S shows that high concentrations of
      acetate increase the catalytic efficiency of the enzyme by as much as 300-fold.
      Under these conditions, the rate of substrate turnover toward a peptidylarginine
      amide substrate equals that of wild-type trypsin. These data demonstrate that the
      well-established requirement for a negatively charged moiety at the base of the
      trypsin specificity pocket may be fulfilled by a noncovalently bound ligand. The
      binding pocket of this variant maintains a trypsin-like conformation, explaining
      the inability of the mutant enzyme to efficiently hydrolyze chymotrypsin
      substrates possessing Phe in the P1 position.

PMID- 8136361
TI  - Characterization of the two anion-recognition sites of glyceraldehyde-3-phosphate
      dehydrogenase from Bacillus stearothermophilus by site-directed mutagenesis and
      chemical modification.
AB  - The active site of the glycolytic glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) contains two anion recognition sites which have been attributed to the
      phosphate binding of the substrates, namely, glyceraldehyde 3-phosphate (Ps site)
      and inorganic phosphate (Pi site) [Moras et al. (1975) J. Biol. Chem. 250, 9137
      9162]. In order to probe the role of both sites during the catalytic event, Arg
      195 from the Pi site and Arg 231 from the Ps site of the Bacillus
      stearothermophilus enzyme have been changed to Leu and Gly, respectively, by site
      directed mutagenesis. A comparative study of the chemical reactivity of the
      mutants and wild type toward 2,3-butanedione revealed a similarly high reactivity
      only for the R195L mutant and wild type, suggesting that only Arg 231 is
      chemically reactive toward 2,3-butanedione and that its reactivity is not
      influenced by the presence of the residue Arg 195, which is only 4 A distant. The
      kinetic consequences of the mutations were also analyzed for the consecutive
      steps in the forward catalytic reaction. The replacement of Arg 195 by Leu leads
      to a marked decrease of the rate of the first steps of the reaction which lead to
      the acylenzyme formation, in particular, the rate of enzyme-substrate
      association, while these steps occur at a similar or higher rate when Arg 231 is
      replaced by Gly. Furthermore, the mutations R195L and R231G also result in a 550
      fold and 16,400-fold decrease in the second-order rate constant of
      phosphorolysis. This step becomes rate-determining for the R195L mutant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8136362
TI  - Crystallographic structures of thrombin complexed with thrombin receptor
      peptides: existence of expected and novel binding modes.
AB  - Many of the vital actions of thrombin on platelets and other cells appear to be
      mediated by the recently cloned seven-transmembrane-domain thrombin receptor.
      Thrombin activates this receptor by a novel proteolytic mechanism. The amino
      terminal exodomain of the receptor contains the sequence LDPRSFLLRNPNDKYEPF.
      Structure-activity studies with mutant receptors and receptor peptides suggest
      that this sequence binds to thrombin at two sites: LDPR with the active center of
      thrombin and KYEPF with the fibrinogen recognition exosite of thrombin. Thrombin
      then cleaves the Arg41-Ser42 bond to unmask a new amino terminus, which functions
      as a tethered peptide ligand binding to as yet undefined sites within the body of
      the receptor to effect receptor activation. We have determined eight crystal
      structures of thrombin complexed with receptor-based peptides. Each of the two
      components of the bidentate docking model was captured in individual cocrystals.
      In one crystal type, the LDPR sequence docked in the active center of thrombin in
      a manner analogous to d-PheProArg chloromethyl ketone. In other crystals, the
      KYEPF sequence bound in the fibrinogen anion binding exosite of thrombin in a
      manner analogous to the DFEEI sequence of the carboxylate-terminal peptide of
      hirudin. Strikingly, however, generation of a single crystal that includes both
      components of the anticipated bidentate binding mode was not achieved, apparently
      because the peptides have a dominant solution S-like conformation that does not
      bind in a productive way at the active center. This peptide structure apparently
      favored a novel alternative mode of receptor peptide-thrombin interaction in
      which the receptor peptides formed an intermolecular bridge between neighboring
      thrombin molecules, resulting in an infinite peptide thrombin chain in crystals.
      In this structure, the KYEPF sequence docked in the expected manner at the
      exosite of one thrombin molecule, but the LDPR sequence docked in an unusual
      nonproductive mode with the active center of a neighboring molecule. Mutations
      that removed important determinants of the S-like receptor peptide structure
      underlying the bridging mode in the receptor itself did not significantly alter
      thrombin signaling. Additionally, a comparison of receptor density to the
      responsiveness of a cell did not support a role for receptor oligomerization in
      signaling. The physiological role for this unexpected intermolecular binding
      mode, if any, remains to be identified.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8136363
TI  - Deuterium solid-state nuclear magnetic resonance studies of methyl group dynamics
      in bacteriorhodopsin and retinal model compounds: evidence for a 6-s-trans
      chromophore in the protein.
AB  - Solid-state deuterium NMR spectroscopy is used to examine the dynamic behavior of
      18-CD3 methyl groups in microcrystalline 6-s-cis-retinoic acid (triclinic) and 6
      s-trans-retinoic acid (monoclinic) model compounds, as well as in the membrane
      protein bacteriorhodopsin (bR), regenerated with CD3-labeled retinal. Temperature
      dependent quadrupolar echo line shapes and T1 anisotropy measurements were used
      to characterize activation energies for 3-fold hopping motion of the methyl
      groups. These data provide supporting evidence that the conformation of the
      retinal chromophore in bR is 6-s-trans. The 6-s-cis conformer is characterized by
      strong eclipsing interactions between the 8-C proton and the 18-C methyl group
      protons; the 18-CD3 group shows an activation energy barrier for methyl 3-fold
      hopping of 14.5 +/- 1 kJ/mol. In contrast, the 18-CD3 group in the 6-s-trans
      isomer shows a considerably lower activation energy barrier of 5 +/- 1 kJ/mol. In
      bR, it is possible to obtain an approximate activation energy of 9 kJ/mol. This
      data is inconsistent with a 6-s-cis conformer but is consistent with the
      existence of a 6-s-trans-retinal Schiff base in bR with some interaction with the
      protein matrix. These results suggest that methyl rotor motions can be used to
      probe the van der Waals contact between a ligand and a protein binding pocket.
      The 6-s-trans conformer of the [16,17-(CD3)2]retinal in frozen hexane exhibits a
      major kinetic component with an activation energy barrier of of 14 -/+ 2
      kJ/mol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136364
TI  - Multinuclear, multidimensional NMR studies of Anabaena 7120 heterocyst
      ferredoxin. Sequence-specific resonance assignments and secondary structure of
      the oxidized form in solution.
AB  - Sequence-specific assignments were determined for the diamagnetic proton
      resonances from recombinant Anabaena 7120 heterocyst ferredoxin (M(r) = 11,000)
      produced in Escherichia coli. Several samples selectively labeled with nitrogen
      15 were prepared for use in two-dimensional heteronuclear multiple quantum
      coherence (HMQC) [Muller, L. (1979) J. Am. Chem. Soc. 101, 4481-4484]
      experiments. A sample uniformly labeled with nitrogen-15 was also prepared and
      used in two three-dimensional experiments: NOESY-HMQC and TOCSY-HMQC [Zuiderweg,
      E. R. P., & Fesik, S. W. (1989) Biochemistry 28, 2387-2391; Marion, D., Ikura,
      M., Tsuchudin, R., & Bax, A. (1989) J. Magn. Reson. 85, 393-399]. The sequential
      assignment strategy relied on the detection of 15N-edited interresidue 1H alpha
      i/1HNi+1 NOE connectivities. Starting points and checks were provided by HMQC
      spectra of the selectively labeled samples. A sample doubly labeled with carbon
      13 and nitrogen-15 was also prepared and used in three triple-resonance
      experiments: HNCA, HNCO, and HN(CO)CA [Ikura, M., Kay, L. E., & Bax, A. (1990)
      Biochemistry 29, 4659-4667; Kay, L. E., Ikura, M., Tschudin, R., & Bax, A. (1990)
      J. Magn. Reson. 89, 496-514]. The HNCA and HN(CO)CA spectra, which were used to
      confirm assignments from NOE connectivities, provided independent sequential
      assignments from spin couplings. Resonances from 18 residues were not seen in the
      diamagnetic region of the NMR spectrum. Several of these residues are very close
      to the [2Fe-2S] cluster, and their absence is explained by paramagnetic
      broadening and/or shifting.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136365
TI  - Structural and dynamic properties of the Fv fragment and the single-chain Fv
      fragment of an antibody in solution investigated by heteronuclear three
      dimensional NMR spectroscopy.
AB  - Fv fragments, heterodimers of the variable light (VL) and variable heavy chain
      (VH) domains, are the smallest functional antibody units with molecular masses of
      approximately 26 kDa. The structural and dynamic properties of the Fv fragment
      and the corresponding single-chain Fv fragment (scFv: VH-linker-VL, 252 amino
      acids) of the phosphorylcholine-binding antibody McPC603 in the presence of
      hapten have been studied in solution by heteronuclear multidimensional NMR
      spectroscopy. Both 15N TOCSY-HMQC and triple-resonance experiments (HNCA and
      HN(CA)H, with 15N-13C-labeled protein) gave poor spectra, due to short T2
      relaxation times for most of the backbone 1H, 15N, and 13C alpha atoms. The
      assignment procedure therefore relied upon the combination of amino acid and
      domain (VL) specifically labeled spectra and the 3D NOESY-HMQC spectrum of the
      uniformly 15N labeled Fv and scFv fragments. Approximately 80% of the 15N and 1H
      backbone and 60% of the 1H side-chain resonances have been assigned. Short- and
      long-range NOEs were used to determine the extent of beta-sheet structure and
      were compared to the X-ray crystallographic data. The 1H-15N NOE data indicate
      that the scFv backbone has a well-defined structure of limited conformational
      flexibility. However, the linker of the scFv fragment exhibits substantial fast
      internal motion (on the picosecond to nanosecond time scale) compared with the
      overall rotational correlation time of the whole molecule. Several residues in
      the CDRs, in turns, or at the C-terminal end of the protein have smaller NOEs,
      reflecting some degree of rapid motion in the protein backbone.

PMID- 8136366
TI  - Thallium-205 and carbon-13 NMR studies of human sero- and chicken ovotransferrin.
AB  - We have examined the binding of Tl3+ to human serotransferrin and chicken
      ovotransferrin in the presence of carbonate and oxalate by 205Tl and 13C NMR
      spectroscopy. With carbonate as the synergistic anion, one observes two 205Tl NMR
      signals due to the bound metal ion in the two high-affinity iron-binding sites of
      each protein. When the same adducts are prepared with 13C-labeled carbonate, one
      finds two closely spaced doublets in the carbonyl region of the 13C NMR spectrum
      of serotransferrin; these correspond to the labeled anion directly bound to the
      metal ion in both sites of the protein. The analogous resonances in
      ovotransferrin are completely degenerate, and only one doublet can be detected.
      The magnitudes of the spin-spin coupling between the bound metal ion and
      carbonate range from 2J(205Tl-13C) approximately 270 to 290 Hz. We have used the
      proteolytic half-molecules of ovotransferrin and the recombinant N-terminal half
      molecule of serotransferrin to assign the 205Tl and 13C NMR signals due to the
      bound metal ion and anion in both proteins. From titration studies, we found that
      Tl3+ is bound with a greater affinity at the C-terminal site of serotransferrin,
      whereas no site preference can be noted for ovotransferrin. When oxalate is used
      as the anion instead of carbonate, the 205Tl NMR signals arising from the bound
      metal ion in the sites of ovotransferrin are shifted downfield and become almost
      degenerate. A very complex pattern of resonances is observed for bound 13C2O4(2-)
      in the 13C NMR spectra of both proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136367
TI  - Energetics of ribonuclease T1 structure.
AB  - The energetics of thermal denaturation of two isoforms of ribonuclease T1 (Gln25
      and Lys25) in various solvents have been studied by differential scanning
      calorimetry. It has been shown that the thermal transition of both forms of RNase
      T1 is strongly affected by slow kinetics, which cause an apparent deviation of
      the transition from a simple two-state model. By decreasing the heating rate or
      increasing the transition temperature, the denaturation of RNase approaches an
      equilibrium two-state transition. This permits determination of the thermodynamic
      parameters characterizing unfolding of the native structure. These thermodynamic
      parameters were correlated with the structural features of protein. Analysis of
      different contributions to the stability of RNase T1 shows that van der Waals
      interactions and hydrogen bonding are the major contributors to the
      conformational stability of the protein.

PMID- 8136368
TI  - Hepatic beta-oxidation of 3-phenylpropionic acid and the stereospecific
      dehydration of (R)- and (S)-3-hydroxy-3-phenylpropionyl-CoA by different enoyl
      CoA hydratases.
AB  - The hepatic beta-oxidation of 3-phenylpropionic acid (PPA) was studied by the use
      of subcellular fractions and purified enzymes with the aim of characterizing
      intermediates and the subcellular location of this pathway. Respiration
      measurements with coupled rat liver mitochondria indicate that PPA is efficiently
      metabolized by mitochondrial beta-oxidation. In contrast, the peroxisomal beta
      oxidation of this compound is at best a very slow process, as evidenced by the
      low activity of peroxisomal acyl-CoA oxidase toward 3-phenylpropionyl-CoA. In
      mitochondria, 3-phenylpropionyl-CoA is effectively dehydrogenated to cinnamoyl
      CoA, which is only slowly converted to benzoylacetyl-CoA due to the unfavorable
      equilibrium of the hydration of cinnamoyl-CoA to 3-hydroxy-3-phenylpropionyl-CoA.
      Benzoylacetyl-CoA is a substrate of 3-ketoacyl-CoA thiolase. The dehydration of 3
      hydroxy-3-phenylpropionyl-CoA to cinnamoyl-CoA forms the basis for a sensitive
      and stereospecific assay of enoyl-CoA hydratases. The progress of this reaction,
      which proceeds to near completion, can be measured spectrophotometrically at 308
      nm. Soluble mitochondrial and peroxisomal enoyl-CoA hydratases only act on the
      (R,L) isomer, whereas the peroxisomal D-3-hydroxyacyl-CoA dehydratase is specific
      for the (S,D) isomer. Both substrates can be easily prepared from the
      commercially available enantiomeric acids. It is concluded that PPA, a key
      compound in Knopp's classical study that led him to formulate the principle of
      beta-oxidation, is overwhelmingly, if not completely, degraded by mitochondrial
      beta-oxidation.

PMID- 8136369
TI  - Recombinant liver fatty acid binding protein interacts with fatty acyl-coenzyme
      A.
AB  - Rat liver fatty acid binding protein (L-FABP) and rat intestine fatty acid
      binding protein (I-FABP) are homologous proteins which are both found in
      intestinal epithelial cells. It was once well accepted that liver fatty acid
      binding protein bound fatty acyl-CoAs, but the recent finding of a novel acyl-CoA
      binding protein (ACBP) in preparations of L-FABP has challenged the role of FABPs
      in acyl-CoA metabolism. Prior to the discovery of ACBP, L-FABP preparations from
      liver were shown to modulate the rate of fatty acyl-CoA synthesis (Burrier et
      al., 1987) and their conversion to phospholipids (Bordewick et al., 1989).
      Studies using FABPs free of ACBP are needed to determine the role of I-FABP and L
      FABP in fatty acyl-CoA metabolism. In this study, highly pure recombinant L-FABP
      and I-FABP were used first to establish binding to fatty acyl-CoAs and then to
      examine the effects of these FABPs on microsomal phosphatidic acid synthesis. The
      standard Lipidex-1000 binding assay using [14C]oleoyl-CoA and a new fluorescence
      binding assay using the fluorescent fatty acyl-CoA cis-parinaroyl-CoA were used
      to determine binding. The results of these assays indicate that L-FABP binds
      fatty acyl-CoAs at two sites with a high-affinity Kd = 3-14 microM. These binding
      assays showed that I-FABP has a much lower affinity for fatty acyl-CoAs than does
      L-FABP. Furthermore, in vitro only L-FABP significantly increases the rate of
      incorporation of oleoyl-CoA into lysophosphatidic acid and phosphatidic acid.

PMID- 8136370
TI  - Structural domains of apolipoprotein(a) and its interaction with apolipoprotein B
      100 in the lipoprotein(a) particle.
AB  - The structural domains of human apolipoprotein(a) [apo(a)] and its interaction
      with apolipoprotein B-100 (apo B-100) in the lipoprotein(a) [Lp(a)] particle were
      investigated by limited proteolysis with thermolysin and cathepsin D. We
      characterized the proteolytic products by sodium dodecyl sulfate-polyacrylamide
      gradient gel electrophoresis, followed by immunoblotting using different
      antibodies. For apo B-100 in Lp(a), the digestion patterns were found to be
      identical to those previously described [Chen et al. (1989) J. Biol. Chem. 264,
      14369-14375; Chen et al. (1991) J. Biol. Chem. 266, 12581-12587] for apo B-100 in
      LDL. Thus, we compared the digestion patterns of apo B-100 in Lp(a) resolved
      under reducing and nonreducing migrating conditions. Using an antibody specific
      for a synthetic peptide of apo B-100 (residues 4004-4021), we confirmed that apo
      B-100 was linked to apo(a) by its C-terminal end. Various Lp(a)s isolated from
      several donors, and containing different isoforms, were used to study the
      structural domains of apo(a). Using the same procedure as for apo B-100, several
      common features were found for the different isoforms. (1) Apo(a) can be cleaved
      into two structural domains: one was of constant size (170 kDa) and was linked to
      apo B-100. Using an antibody specifically directed against kringle V, we
      demonstrated that this fragment corresponded to the C-terminal part of apo(a).
      (2) The other domain, whose size varied according to the digested apo(a) isoform,
      was not linked to apo B-100.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136371
TI  - Orientational and aggregational states of magainin 2 in phospholipid bilayers.
AB  - Magainins from Xenopus skin are antimicrobial peptides with broad spectra, and
      their action mechanisms are considered to be the permeabilization of bacterial
      membranes. To elucidate their molecular mechanisms, three analog peptides of
      magainin 2, each having a Trp residue substituted for Phe at the 5th, 12th, or
      16th position, were synthesized, and their interactions with acidic phospholipid
      membranes were investigated by fluorescence. The Trp substitution did not
      significantly affect the properties of the parent peptide. The binding isotherms
      of these peptides to the membranes, which were obtained on the basis of
      fluorescence changes upon membrane binding of the peptides, were sigmoidal,
      suggesting the association of the bound peptide molecules. A quantitative
      analysis indicated that the formed aggregate is a dimer. The observation that the
      initial rate constant of magainin 2 induced leakage of calcein from liposomes was
      dependent on the fourth power of the peptide concentration demonstrates the
      formation of a tetrameric pore. A blue shift and intensity enhancement of Trp
      fluorescence in the presence of the membranes indicate that those Trp residues
      are buried in the hydrophobic region of the bilayers. Furthermore, the depths of
      the Trp residues, which were determined using the n-doxylphosphatidylcholine
      quenching technique, were about 10 A from the bilayer center irrespective of the
      peptide aggregational state. Thus, it was concluded that the orientation of the
      magainin 2 alpha-helix is parallel to the membrane surface. A model of the pore
      formation will be proposed on the basis of these observations.

PMID- 8136372
TI  - Phosphorylation of rabbit reticulocyte guanine nucleotide exchange factor in
      vivo. Identification of putative casein kinase II phosphorylation sites.
AB  - The guanine nucleotide exchange factor (GEF) is a multi-subunit protein which
      catalyzes the exchange of GDP for GTP in eukaryotic chain initiation factor 2.
      Phosphorylation of the 82-kDa subunit of GEF in vitro by casein kinase II (CK-II)
      is associated with a 5-fold increase in nucleotide exchange activity. However,
      phosphorylation of GEF in vivo has not been studied, and the kinase(s) that
      phosphorylate GEF have not been identified. The 82-kDa subunit of GEF was
      partially sequenced, and a synthetic peptide was used to generate polyclonal anti
      peptide antibodies that react specifically with this subunit. To examine the
      phosphorylation of GEF in intact cells, the protein was isolated and purified
      extensively from metabolically 32P-labeled rabbit reticulocytes. Only the 82-kDa
      subunit was found to be phosphorylated, and on Western blots the anti-peptide
      antisera reacted specifically with the labeled subunit. Phosphoamino acid
      analysis indicated that phosphorylation occurred exclusively on Ser residues.
      Digestion with cyanogen bromide of in vivo labeled protein and GEF phosphorylated
      in vitro by CK-II produced comparable phosphopeptide maps. However, additional
      phosphopeptide bands were also observed with GEF derived from intact cells.
      Sequence analysis obtained by Edman degradation of the phosphopeptides was
      compared with the deduced amino acid sequence of a cloned 82-kDa subunit of GEF
      [Bushman, J. L., Asuru, A. I., Matts, R. L., & Hinnenbusch, A. G. (1993) Mol.
      Cell. Biol. 13, 1920-1932]. Putative sites of phosphorylation were identified at
      Ser 703 and/or 704, which contain the sequence S(P)XXD, a CK-II consensus
      recognition motif.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136373
TI  - Inhibition of nuclear protein binding to the human Ki-ras promoter by triplex
      forming oligonucleotides.
AB  - The human Ki-ras promoter contains a 22 base pair homopurine.homopyrimidine
      (pur.pyr) motif within a region that is nuclease-hypersensitive in both native
      chromatin and supercoiled plasmids. Gel mobility shift analysis and competition
      experiments show that this pur.pyr motif binds a nuclear protein(s) in a sequence
      specific manner. Several observations suggest that the nuclear protein may be an
      important regulatory factor. Gel mobility shift analysis and DNase I footprinting
      demonstrate that oligonucleotides can be targeted to this motif forming sequence
      specific purine*purine.pyrimidine (pur*pur.pyr) or mixed purine/pyrimidine*purine
      pyrimidine (pur/pyr*pur.pyr) intermolecular triple helices through guanine (G)
      recognition of guanine.cytosine (G.C) base pairs and either adenine (A) or
      thymine (T) recognition of adenine-thymine (A.T) base pairs in the target
      sequence. Triple helices containing either T*A.T or A*A.T triplets are formed
      exclusively with oligonucleotides antiparallel to the homopurine target strand.
      The affinity of an oligonucleotide which forms T*A.T triplets is approximately
      equal to, or slightly greater than, the affinity of an oligonucleotide which
      forms A*A.T triplets. Oligonucleotide-directed triplex formation inhibits
      sequence-specific nuclear protein binding to the K-ras promoter. These
      observations suggest that triplex formation by the oligonucleotides described
      here may provide a means to specifically inhibit transcription of the K-ras
      oncogene.

PMID- 8136374
TI  - Telomeric protein-DNA point contacts identified by photo-cross-linking using 5
      bromodeoxyuridine.
AB  - The Oxytricha telomere protein specifically recognizes single-stranded telomeric
      DNA, forming an extremely salt resistant and kinetically stable nucleoprotein
      complex. The absence of information on how this heterodimeric protein binds to
      DNA prompted this photo-cross-linking study. Multiple protein-DNA photo-cross
      links are formed upon UV irradiation of Oxytricha telomeres reconstituted with a
      synthetic oligonucleotide terminating in 5'
      T16T15T14T13G12G11G10G9T8T7T6T5G4G3G2G1-3'. Site-specific substitution of certain
      nucleotides with 5-bromodeoxyuridine (BrdU) greatly increased the photo-cross
      linking yield, each substitution favoring a specific protein-DNA cross-link. For
      example, substitution of BrdU for T7 resulted in 25% cross-linking of the bound
      DNA, a 10-fold increase over the unsubstituted DNA. Both subunits of the telomere
      protein cross-link to, and are therefore near, the DNA. Three point contacts
      within this nucleoprotein complex, involving the alpha subunit, were established
      using BrdU substitution: Tyr239, Tyr142, and His292 cross-link to G3, T15, and
      T7, respectively. One photo-cross-link, Tyr239-G3, occurs amid a short acidic
      stretch of the alpha subunit, counter to expectations for amino acids that
      approach the polyanionic DNA. The two remaining cross-links are to amino acids in
      hydrophobic regions of the primary polypeptide sequence, consistent with the
      hypothesis that hydrophobic interactions account for the salt resistance (> 2 M
      NaCl) of this protein-DNA complex. These two photo-cross-links suggest that the
      telomere protein may bind telomeric single-stranded DNA by intercalation of
      aromatic residues into a nucleotide lattice.

PMID- 8136375
TI  - A kinetic and thermodynamic framework for the hammerhead ribozyme reaction.
AB  - A hammerhead ribozyme (HH16) with eight potential base pairs in each of the
      substrate recognition helices stabilized product binding sufficiently to enable
      investigation of the ligation of oligonucleotides bound to the ribozyme. All
      individual rate constants for product association and dissociation were
      determined. The following conclusions were obtained for HH16 from the analysis
      performed at 50 mM Tris, pH 7.5, 10 mM MgCl2, and 25 degrees C. (1) HH16 cleaves
      bound substrate with a rate constant of k2 = 1 min-1, similar to rate constants
      obtained with other hammerhead ribozymes. (2) k-2, the rate of ligation of the 5'
      product and 3' product to form substrate, equaled 0.008 min-1, indicating an
      approximately 100-fold preference for the formation of products on the ribozyme.
      This internal equilibrium, compared with that for the overall solution reaction,
      gives an effective concentration (EC) of 10(-2) M for the two products bound to
      the ribozyme. This low EC suggests that upon cleavage of S the hammerhead complex
      acquires a "floppiness" which provides an entropic advantage for the formation of
      products on the ribozyme. (3) Product and substrate association rate constants
      were in the range of 10(7)-10(8) M-1 min-1, comparable to values determined for
      short helices. (4) The stabilities of ribozyme/product complexes were similar to
      affinities predicted from helix-coil transitions of simple RNA duplexes,
      providing no indication of additional tertiary interactions. The products, P1 and
      P2, stabilize one another 4-fold on the ribozyme. (5) The dissociation constant
      for the binding of the substrate to the ribozyme was estimated to be about 10(
      17) M. These results allowed the construction of a free energy profile for the
      reaction of HH16, and provide a basis for future mechanistic studies.

PMID- 8136376
TI  - Raman microspectroscopic study of low-pH-induced changes in DNA structure of
      polytene chromosomes.
AB  - The effects of low-pH treatments on DNA structure in polytene chromosomes of
      Chironomus thummi thummi have been studied by Raman microspectroscopy.
      Measurements were carried out on chromosomes at low pH and on chromosomes
      reneutralized after a short exposure to low pH. Protonation of adenine residues
      and subsequent unpairing of adenine (A) and thymine (T) were found to commence
      already above pH 3.6 and are completed at pH 2.2. Protonation of the cytosine
      guanine base pair also starts above pH 3.6. It leads to an intermediate
      protonated, most likely Hoogsteen-type, guanine-cytosine base pair. Unpairing of
      G and C residues starts between pH 2.6 and 2.2 and continues below pH 2.2. Brief
      treatment of chromosomes at a pH < or = 2.2, i.e., at a pH where both AT and GC
      base pairs are disrupted, was found to lead to irreversible changes in DNA
      conformation upon return to neutral pH. These were most pronounced after
      treatment with 45% acetic acid. More than 10% of the A and T residues was found
      to have adopted a non-B-DNA conformation. Evidence was found for denaturation of
      the B-form backbone. The amount of protein extracted from the chromosomes was
      strongly pH-dependent. Treatment at pH 3.6 did not cause noticeable protein
      extraction, while treatment with 45% acetic acid extracted more than 50% (by
      weight) of the chromosomal proteins.

PMID- 8136377
TI  - Determination of free energies of N-capping in alpha-helices by modification of
      the Lifson-Roig helix-coil therapy to include N- and C-capping.
AB  - We have previously shown that varying the N-terminal amino acid in alpha-helical
      peptides can cause large variations in helix content (Chakrabartty et al.,
      1993a). The Lifson-Roig theory for the helix-coil transition predicts, however,
      that substitutions at the N-terminus in an unacetylated peptide should have no
      effect on alpha-helix stability. We have therefore modified the theory to include
      these N-capping effects by assigning a statistical weight (the "n-value") to the
      amino acid immediately preceding a stretch of helical residues. The n-value
      measures the N-capping propensity of an amino acid, and like the helix propensity
      (w-value), it is independent of neighboring residues or positions in sequence.
      The new theory was used, with the experimental data for these substitutions, to
      calculate n-values and, hence, free energies for N-capping for the amino acids
      Gln, Ala, Val, Met, Pro, Ile, Leu, Thr, Gly, Ser, and Asn as well as for the
      acetyl group, which is commonly used to cap peptides. The free energies vary by
      approximately 1 kcal mol-1 from Gln (worst) to Asn (best), and the acetyl group
      is nearly as effective as Asn. N-Capping free energies were also found for Leu,
      Thr, Gly, Ser, and Asn when the N-terminus is charged at pH 5. The unfavorable
      effect of protonation of the N-terminus in an alpha-helix was found to be
      approximately 0.5 kcal mol-1. Our results agree well with a survey of N-capping
      preferences from protein crystal structures and are compared to results from site
      directed mutagenesis of N-caps in proteins.

PMID- 8136378
TI  - The formation of diselenide bridges in proteins by incorporation of
      selenocysteine residues: biosynthesis and characterization of (Se)2-thioredoxin.
AB  - A system was devised which allows the efficient substitution of cysteine residues
      in a protein by selenocysteine. It involves overexpression of the respective gene
      with the aid of the T7 promotor/polymerase system in a cysteine auxotrophic
      strain. The induction of the T7 polymerase formation was performed in cysteine
      supplemented medium followed by wash-out of the cysteine and production of the
      desired gene product in the presence of selenocysteine. The system was applied to
      substitute the two cysteine residues in Escherichia coli thioredoxin. Analysis of
      the purified gene product by electrospray mass spectrometry and HPLC revealed
      that both cysteine residues were replaced in approximately 75-80% of the protein,
      only one cysteine residue was substituted in about 5-10%, and no substitution had
      taken place in 12-17% of the protein. The occurrence of diselenide, seleno
      sulfur, and disulfide bridges in the purified gene product was revealed by ES/MS
      and chemical modification studies. The diselenide bridge represents an entity in
      protein structures which has hitherto not been described. The redox property of
      the selenocysteine variant of thioredoxin [(Se)2-thioredoxin] was found to be
      substantially different from that of thioredoxin. Only the latter could be
      reduced under native conditions in the presence of an excess of beta
      mercaptoethanol. The oxidized (Se)2-thioredoxin was then separated from the
      selectively reduced and carboxymethylated protein by anion-exchange
      chromatography. The purity of the isolated (Se)2-thioredoxin was at least 92%.

PMID- 8136379
TI  - Kinetic characteristics of phosphofructokinase from Bacillus stearothermophilus:
      MgATP nonallosterically inhibits the enzyme.
AB  - The kinetic mechanism of phosphofructokinase from Bacillus sterothermophilus has
      been investigated using steady-state measurements. The double-reciprocal patterns
      observed for initial velocity, product inhibition, and mixed alternate substrate
      studies of the reverse reaction establish that the mechanism involves rapid
      equilibrium random binding of substrates and the formation of an abortive complex
      composed of enzyme, MgADP, and fructose 6-phosphate (E-MgADP-Fru-6P). Initial
      velocity patterns for the forward reaction show significant nonlinearity and
      resemble those seen for competitive substrate (MgATP) inhibition of an enzyme
      that obeys a random mechanism. A mutant BsPFK enzyme (GV212) was used to show
      that the inhibition is not due to MgATP binding in the effector site. Product and
      dead-end inhibition studies of the forward reaction are consistent with a random
      mechanism, after taking into account the effects of substrate inhibition by
      MgATP. Initial velocity measurements at low MgATP concentration show that the
      binding of MgATP is not a rapid-equilibrium process; i.e., the rate of catalysis
      is faster than the rate of substrate binding. It is concluded that the kinetic
      mechanism of the forward reaction is sequential random, with the rate of MgATP
      binding slower than the catalytic rate. A model is presented that incorporates
      these results and proposes that substrate binding proceeds through two
      alternative pathways, one of which is kinetically disfavored. The observed MgATP
      substrate inhibition arises from both reaction flux through the disfavored
      pathway and, to some extent, abortive binding of MgATP in the Fru-6P site.

PMID- 8136380
TI  - Complementary DNA cloning and kinetic characterization of a novel intracellular
      serine proteinase inhibitor: mechanism of action with trypsin and factor Xa as
      model proteinases.
AB  - The full-length cDNA encoding a novel human intracellular serine proteinase
      inhibitor has been sequenced and found to encode a 376 amino acid protein (M(r)
      approximately 42.5K) that we designate as cytoplasmic antiproteinase. Analysis of
      the primary structure revealed that the cytoplasmic antiproteinase has the
      majority of structural motifs conserved among the greater superfamily of serine
      proteinase inhibitors, or serpins. On the basis of several criteria such as amino
      acid identity and the absence of a classical N-terminal signal peptide, the
      cytoplasmic antiproteinase represents a new member of the intracellular serpin
      family. Further inspection of the cytoplasmic antiproteinase amino acid sequence
      identified three potential N-glycosylation sites and Arg341-Cys342 as the
      reactive site P1-P1' residues, respectively. We have also employed the slow
      binding kinetic approach to detail the mechanism of bovine trypsin and human
      factor Xa inhibition by the novel cytoplasmic antiproteinase. Inhibition of
      trypsin by the cytoplasmic antiproteinase was preceded by a two-step mechanism
      corresponding to the formation of an initial loose complex, followed by an
      isomerization step to a more stable, tight complex. The binding of the
      cytoplasmic antiproteinase to trypsin occurred with a second-order association
      rate constant of 2.8 x 10(6) M-1 s-1 and an overall equilibrium constant of 22.5
      pM, demonstrating that the factor is a potent inhibitor of this proteinase. Under
      the appropriate conditions, the tight complex between trypsin and the cytoplasmic
      inhibitor was reversible, indicated by an exponential regeneration of proteinase
      amidolytic activity from the preformed complex. Therefore, the tight complex
      appears to be stabilized predominantly by reversible bonds that form between
      trypsin and the cytoplasmic inhibitor. In contrast to the inhibition of trypsin,
      the inhibition of factor Xa amidolytic activity by the cytoplasmic antiproteinase
      followed a single-step binding mechanism. The apparent first-order rate constant
      for factor Xa inhibition was found to increase as a linear function of the
      inhibitor concentration range studied. Formation of the inhibitory complex
      between factor Xa and the cytoplasmic antiproteinase occurred with a second-order
      association rate constant of approximately 1.3 x 10(5) M-1 s-1 and a equilibrium
      constant of 3.7 nM. These findings suggests that the cytoplasmic inhibitor may
      initially encounter significant energy barriers for proper alignment with the
      substrate binding cleft of factor Xa. However, once aligned, the reaction
      proceeds rapidly to a tight factor Xa.inhibitor complex that dissociates at a
      slow rate.

PMID- 8136381
TI  - Exon 11 of the rat cholesterol esterase gene encodes domains important for
      intracellular processing and bile salt-modulated activity of the protein.
AB  - The rat pancreatic cholesterol esterase is a 74,000 molecular weight protein
      encoded by a gene with 10 introns and 11 exons. The last exon of the cholesterol
      esterase gene is the largest and is also the least conserved exon among the
      cholesterol esterase genes of various species. The current study investigates the
      functional role of the exon 11 domain in rat cholesterol esterase. The
      transfection of native cholesterol esterase cDNA into COS cells resulted in an
      enzymatically active cholesterol esterase that was secreted by the cells. In
      contrast, transfection of cholesterol esterase cDNA with 88% of the exon 11
      residues deleted from the sequence resulted in a protein that was not secreted by
      the cells. The cholesterol esterase with deletions in the exon 11 domain retained
      the ability to bind bile salt but was found to be enzymatically inactive. The
      inefficient secretion and the loss of enzyme activity for the truncated protein
      were not due to deletion of the proline-rich repeating units located in the exon
      11 domain at the carboxyl terminus of the cholesterol esterase. The expression of
      rat cholesterol esterase with zero or one proline-rich units resulted in a
      truncated protein that was secreted by the transfected COS cells. The cholesterol
      esterases with reducing numbers of the proline-rich repeating units were also
      active in hydrolyzing p-nitrophenyl butyrate and cholesteryl oleate. The
      cholesterol esterase with fewer proline-rich repeating units were more active
      than the native enzyme in substrate hydrolysis at low bile salt
      concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136382
TI  - Cooperative interaction of divalent metal ions, substrate, and tissue factor with
      factor VIIa.
AB  - Factor VIIa-tissue factor (TF) complex formation in the presence of EDTA or
      divalent cations (Me2+) was investigated. The influence of Me2+ on the amidolytic
      activity of factor VIIa and factor VIIa-TF complex was evaluated using low
      molecular weight synthetic substrates possessing substituted
      aminonaphthalenesulfonamides as detecting groups. Factor VIIa expressed low
      amidolytic activity in the presence of EDTA. In the presence of EDTA and
      saturating concentrations of TF, the amidolytic activity of factor VIIa was
      increased approximately 90-fold. Gel electrophoresis and sedimentation velocity
      studies demonstrated complex formation between factor VIIa and TF in the presence
      of EDTA. Substrate titration curves obtained at fixed factor VIIa and TF
      concentrations gave sigmoidal shapes, indicating that substrates influenced
      factor VIIa amidolytic activity in the presence of TF. In the absence of Me2+,
      the KD,app of the factor VIIa-TF complex was influenced by substrate structure
      and varied from 3.9 to 34 nM. All Me2+ used increased the amidolytic activity of
      factor VIIa approximately 8-fold compared with experiments in the presence of
      EDTA. The KD,app values for factor VIIa-Ca2+ complex and factor VIIa-Mn2+ complex
      were independent of substrate and were 270 and 40 microM, respectively. The
      KD,app for factor VIIa-Mg2+ complex varied from 3 to 12 mM and was substrate
      structure dependent. The presence of TF had no influence upon the KD,app for the
      factor VIIa-Ca2+ complex. The amidolytic activity of factor VIIa was enhanced by
      TF significantly in the presence of Ca2+, and similar results were obtained with
      Mg2+ and Mn2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136383
TI  - [Differentiation of testicular diseases using dynamic MRT].
AB  - Sonography and colour-coded Doppler sonography are the methods of first choice in
      diagnosing tumors of the testes. The present study aimed at resolving whether
      dynamic MRT can improve diagnostic relevance in diseases of the testes compared
      with conventional spin echo images. The testes of 20 healthy volunteers and of 16
      patients of the Department of Urology of the University of Bonn were examined by
      means of MR tomography. Within 12 hours after MR tomography the patients were
      surgically explored, biopsied and if necessary orchiectomised. Results obtained
      with the volunteers were uniform and well reproducible, independent of external
      influences. On comparing the maximal enhancement curves of the examined various
      testicular tumors with the standard values established by examining the healthy
      volunteers, the curves obtained with the malignant testicular tumors were always
      clearly above the chosen confidence range of 3 standard deviations so that
      malignancy diagnosis was easy. However, the degree of maximal enhancement did not
      enable us to arrive at a conclusion in respect of the tumor type or the degree of
      malignancy. The greatest enhancement occurred with the tumor of Sertoli's cell
      which could thus be clearly differentiated against the other malignant testicular
      tumors. Due to masking of the gadolinium effect by haemosiderin deposits,
      haemorrhagica in the tumor tissue should be excluded by means of T2-weighted spin
      echo sequences before following up a suspicion of malignant testicular tumor.
      Benign intratesticular changes could be safely separated from malignant findings
      by means of the maximal enhancement curve lying in the normal range or below the
      curve of the volunteers. As with other organs, dynamic MR tomography yields
      definitely more and better information than conventional MR tomography also in
      the diagnosis of testicular tumours. However, these "pros" do not offset the
      "cons" of high costs of such examinations, so that both conventional sonography
      and angiodynography remain the routine methods of choice. Indication for MR
      examination on suspicion of testicular tumour is therefore confined to cases
      where sonographic findings are clinically equivocal or technically
      unsatisfactory.

PMID- 8136384
TI  - [MRT in degenerative diseases of the cervical spine].
AB  - MRI has grown increasingly important in recent years in diagnosis of degenerative
      disease of the cervical spine, due to improvements of method that have made it a
      valuable diagnostic tool. The following contribution gives a brief introduction
      to the pathophysiology of degenerative changes in the cervical vertebral column
      and to the indications for MRI, describing within the framework of imaging the
      present state of MR examination technique. The ranking of the various gradient
      echo sequences, of the 3D methods and of the administration of contrast media in
      cervical myelopathy and radiculopathy is discussed.

PMID- 8136385
TI  - [A daylight film development system for mammography. Report of clinical
      experience after 4000 examinations (corresponding to 14,000 mammographies].
AB  - From 6/90-2/91 the daylight system EC (Fuji Ltd.), developed only for
      mammography, was used in the Department of Gynaecological Radiology of the
      Radiological Centre of the University of Freiburg for the first time in Germany.
      We examined 4000 patients (respectively 14,000 mammographies). We controlled the
      quality of the x-ray photographs every day (n = 175) and compared the results
      with the controls of quality, which had been carried out from 9/89-5/90 with the
      conventional technique (n = 175). During the entire period of research (9/89
      2/91) at both systems the results of Dmin were inferior to the standard. Using
      the daylight system the measurements of the index of sensitivity were in 91% of
      the cases (n = 160), and the index of contrast in 88% (n = 154) within the range-
      much better than with the conventional system with 74% (130 measurements),
      respectively 70% (123 measurements). We also found an evident advantage of time
      and in future it is to be expected that the conventional system will be replaced
      by the daylight system in mammography.

PMID- 8136386
TI  - [The parameters of image quality of a novel ultra high resolution film-screen
      system].
AB  - A film/screen system is described where the light emission of the intensifying
      screen is in the UV, which is more efficiently absorbed by the film, and hence
      print-through is virtually eliminated. In addition, because of significantly
      higher UV absorption within the screen, MTF is superior to conventional systems
      based on visible light. Thus the overall UV film/screen system has imaging
      efficiency and quality, as measured by the Detective Quantum Efficiency (DQE) and
      the Noise Equivalent Quantum Efficiency (NEQ), with superior characteristics to
      those of conventional systems. These imaging characteristics of the novel systems
      are described here and are compared with those of some conventional systems.

PMID- 8136387
TI  - [Initial experiences with combined balloon angioplasty and rtPA thrombolysis in
      dialysis shunt failure].
AB  - The 23 interventions performed by us on 18 patients had a very high success rate
      both in intraarterial lysis therapy of obstructed haemodialysis shunts and in
      balloon angioplasty (19/23). Shunt failure had to be primarily treated by surgery
      in 3 cases only. The complications were confined to a rupture of a vessel that
      required surgical care. 14 shunts were found to be patent in a total of 18
      patients (18 being of course as small patient group). Our experience leads us to
      believe that patients suffering from shunt insufficiency should always be
      primarily treated endoluminally if angiography confirms that intervention is
      possible. Surgical intervention is always advisable even if the result may
      occasionally be negative in a few rare cases.

PMID- 8136389
TI  - [Hypodense oral intestinal contrasting for the diagnostic optimization of
      abdominal computed tomograms in children].
AB  - 37 children were examined for diagnostic improvement of the oral intestinal
      contrasting images in abdominal computed tomography with a hypodense solution of
      mannitol (n = 23) in comparison with a suspension of BaSO4 (n = 14). Because of
      the hypodense intestinal contrasting images the artifacts of the images induced
      by the bordering surface could be reduced, the condition of fullness of the
      intestine and the judgement of the intestinal wall improved. The parenchymatous
      organs and points of abdominal lymph nodes could be defined and judged more
      easily through the hypodense contrasting images. On the whole the picture quality
      of the computed tomography of the young child could be increased with the
      hypodense solution of mannitol.

PMID- 8136388
TI  - [Computed tomography in malignant primary soft tissue tumors].
AB  - The results of CT examinations in 36 patients suffering from histologically
      confirmed malignant primary tumours of the soft tissues are presented (6
      rhabdomyosarcomas, 4 leiomyosarcomas, 6 liposarcomas, 4 malignant schwannomas, 5
      malignant fibrous histiocytomas, 4 malignant haemangiopericytomas, 3
      angiosarcomas, 1 fibrosarcoma, 1 renal sarcoma, 2 malignant mesenchymal tumours
      without histologically clear classification). The CT image alone will not yield
      information on the type of tumour or on the tumour status. However, CT continues
      to rank in the diagnosis of tumours of the soft tissues and is even superior to
      MR especially in the identification of gas accumulations due to infection in a
      tumour of the soft tissues that is otherwise unclear. Comparing the literature
      conclude that MR is now the imaging method of choice in the diagnosis of soft
      tissue tumours.

PMID- 8136390
TI  - [Bronchiolitis obliterans accompanied by organizing pneumonia: radiologic
      diagnosis in a case of a 22-year-old female].
AB  - Case report of a 22-year old patient with most severe idiopathic bronchiolitis
      obliterans and organising pneumonia. We discuss the diagnostic algorithm and
      emphasise the role of CT.

PMID- 8136391
TI  - [Giant cystosarcoma phylloides: mammographic and sonographic findings in an
      unusual case].
AB  - Cystosarcoma phylloides (also called phylloides tumour) is a rare fibroepithelial
      mixed tumour which accounts for 0.3 to 1% of all breast neoplasms. Diagnosis can
      be strongly suspected after clinical, mammographical and especially sonographical
      findings. Neither mammography nor sonography and even not aspiration cytology can
      be reliably used to differentiate between benign and malignant tumours. In the
      following a patient is presented in whom cystosarcoma phylloides attained, even
      for this kind of tumour, an unusually large dimension.

PMID- 8136392
TI  - [Computed tomographic detection of air in the portal vein--a case report].
AB  - Two cases of portal venous gas (PVG) are presented. One case due to bowel
      infarction and another due to duodenal ulcer perforation complicated by a
      subphrenic abscess. The diagnosis was suggested from plain abdominal radiographs
      and confirmed by unenhanced computed tomography (CT) of the abdomen which is
      superior to demonstrate gas in the portal venous system. The distinction between
      PVG and biliary gas is briefly discussed.

PMID- 8136394
TI  - Nurse anesthesia research: not yet ready for prime time.

PMID- 8136393
TI  - [Tertiary yaws--skeletal manifestations at the distal tibia].
AB  - We describe the case of a 16-year old male patient from African presenting
      tertiary yaws at the distal tibia. Clinical signs, biochemical results and the
      different diagnostic imaging methods are demonstrated. Differential diagnosis and
      therapy are described.

PMID- 8136395
TI  - Ketorolac as a premedicant for coronary artery bypass surgery patients with
      normal ventricles.
AB  - Premedication of patients requiring cardiac surgery should provide adequate
      analgesia, sedation and anxiolysis for the stress and pain associated with
      preoperative preparation and placement of monitoring catheters. Ideally, these
      effects would be achieved without producing respiratory depression and hypoxia,
      which could be life-threatening to patients at risk for myocardial ischemia.
      Ketorolac, a nonsteroidal, antiinflammatory agent, has previously been shown to
      provide postoperative pain relief comparable to that provided by morphine,
      without respiratory depression. This study compared the incidence of arterial
      blood desaturation, respiratory depression, and patient comfort after
      preoperative medication with scopolamine and ketorolac versus scopolamine and
      morphine. Scopolamine and ketorolac premedication provided sedation and analgesia
      comparable to that provided by scopolamine and morphine, without significant
      respiratory depression. Since ketorolac has no central respiratory depressant
      effect, it may be a useful alternative to morphine for premedication in the
      cardiac surgical patient.

PMID- 8136397
TI  - Scope of nursing practice and business relationships between nurses and
      physicians in California: Part 2.

PMID- 8136396
TI  - Discharge time in patients who receive fentanyl or alfentanil for general
      anesthesia.
AB  - Forty ASA I and II patients undergoing elective termination of pregnancy were
      studied. Patients were randomly selected to receive fentanyl or alfentanil.
      Patients received 1 to 2 mg midazolam, 2.0 to 2.5 mg/kg propofol, and 10 to 20
      micrograms/kg alfentanil or 1 to 2 micrograms/kg fentanyl for induction and
      maintenance of anesthesia. In addition all patients were administered 70% N2O and
      30% O2. The time from admission to the post anesthesia recovery unit until
      discharged home was defined as the discharge time. These times were compared
      using the student's t test to determine if there was a significant difference (P
      < .05) between the mean discharge time of the two groups. In addition, each
      patient's total postanesthesia recovery scores were evaluated on admission, at 15
      minutes, and at discharge from the post anesthesia recovery unit. These data were
      analyzed using the Mann-Whitney U test to determine if there was a significant
      difference in the mean rate of recovery in each area observed. The data revealed
      no statistically significant difference between the mean discharge times of the
      two groups or in the total post anesthesia recovery unit recovery scores.

PMID- 8136398
TI  - Anesthesia considerations for anorexia nervosa and bulimia nervosa.
AB  - Anorexia nervosa and bulimia are appearing with increasing frequency in
      preadolescents and adolescents. Eating disorders lead to significant physical
      changes related to starvation and/or purging. These patients should be
      specifically questioned about taking laxatives, diuretics, or amphetamines to
      lose weight. Subclinical abnormalities, coupled with the patient's denial,
      emphasize the need for careful physical examination and laboratory assessment.
      Preexisting electrolyte, cardiovascular, and thermoregulatory alterations must be
      recognized so that an appropriate anesthesia plan can follow.

PMID- 8136399
TI  - Transesophageal echocardiography as an intraoperative monitor.
AB  - Echocardiography is recognized as a excellent diagnostic tool for non-invasive
      cardiac assessment. Recently, transesophageal echocardiography has been utilized
      as an "on line, real time" intraoperative monitoring device in cases where
      patients are at significant risk for intraoperative cardiac ischemia, large
      shifts in hemodynamic parameters, and/or air embolism. This advancement in
      cardiac and hemodynamic intraoperative monitoring is significant as it enables
      early recognition of cardiac ischemia through assessment of cardiac contractility
      and regional wall motion abnormalities; accurate volume status assessment with
      direct monitoring of cardiac chamber volumes, valvular function, and intracardiac
      shunting; and real time assessment of the presence, size, and location of
      intracardiac air. Transesophageal echocardiography is a safe and accurate tool
      enabling early recognition of those physiological intraoperative changes where
      early intervention is critical for improved patient outcome.

PMID- 8136400
TI  - Anaphylactic reaction to intravenous cefazolin.
AB  - Allergic responses to cefazolin occur in approximately 3% to 5% of patients. The
      responsibility of the health care professional includes developing an awareness
      that histamine release in varying degrees can occur with the administration of a
      variety of drugs utilized throughout the perioperative period. The authors
      discuss the cardiopulmonary manifestations resulting from the release of
      histamine during an allergic reaction. Differentiation of diagnosis of the
      causative agent, the effective treatment of the anaphylactic response during
      anesthesia, and preventive measures to reduce anesthesia morbidity are examined.

PMID- 8136401
TI  - Isoflurane and mivacurium chloride neuromuscular blockade in patients with
      myasthenia gravis.
AB  - The relaxograph findings are presented in two patients. In the first, isoflurane
      alone is administered, and mivacurium with isoflurane is administered to the
      second patient with myasthenia gravis. A significantly lower dose of mivacurium
      is required. It was noticed that the T4:T1 ratio was 100% after mivacurium and
      reversal agent, but T1 did not return to normal. In the patient that only
      received isoflurane, T1 was 60% to 70% of the baseline, indicating the
      neuromuscular blocking effects of isoflurane. These cases illustrate that
      inhalation anesthetics are adequate for muscle relaxant effects, and if
      neuromuscular blockers are necessary, then a lower dose of nondepolarizer should
      be administered, and the patient carefully monitored. Mivacurium appears to be an
      ideal agent for neuromuscular blockade in myasthenia gravis as long as careful
      neuromuscular blockade is performed.

PMID- 8136403
TI  - In the case of the emergency carotid endarterectomy, the anesthesia plan.

PMID- 8136402
TI  - Drug-induced methemoglobinemia in a healthy 20-year-old soldier undergoing
      shoulder surgery.
AB  - A young adult male, ASA status I, presented for left shoulder arthroscopy. His
      medications included indocin for shoulder pain and chloroquine, an antimalarial.
      He was anesthetized using propofol, midazolam, fentanyl, and a relaxant. His
      initial oximetry reading of 94% saturation was erroneously attributed to
      shivering and to the fact that the oximeter clip was distal to the blood pressure
      cuff on the right upper extremity, necessitated by proximity of surgery. The
      initial saturation level of 94% was persistent throughout the case. The
      methemoglobin level drawn immediately postoperatively was 9%. The patient was
      treated with methylene blue which resulted in an improvement in oxygen saturation
      to 98%. His remaining postoperative course was uneventful, and he was released
      one day later.

PMID- 8136404
TI  - A nonstationary Poisson point process describes the sequence of action potentials
      over long time scales in lateral-superior-olive auditory neurons.
AB  - The behavior of lateral-superior-olive (LSO) auditory neurons over large time
      scales was investigated. Of particular interest was the determination as to
      whether LSO neurons exhibit the same type of fractal behavior as that observed in
      primary VIII-nerve auditory neurons. It has been suggested that this fractal
      behavior, apparent on long time scales, may play a role in optimally coding
      natural sounds. We found that a nonfractal model, the nonstationary dead-time
      modified Poisson point process (DTMP), describes the LSO firing patterns well for
      time scales greater than a few tens of milliseconds, a region where the specific
      details of refractoriness are unimportant. The rate is given by the sum of two
      decaying exponential functions. The process is completely specified by the
      initial values and time constants of the two exponentials and by the dead-time
      relation. Specific measures of the firing patterns investigated were the
      interspike-interval (ISI) histogram, the Fano-factor time curve (FFC), and the
      serial count correlation coefficient (SCC) with the number of action potentials
      in successive counting times serving as the random variable. For all the data
      sets we examined, the latter portion of the recording was well approximated by a
      single exponential rate function since the initial exponential portion rapidly
      decreases to a negligible value. Analytical expressions available for the
      statistics of a DTMP with a single exponential rate function can therefore be
      used for this portion of the data. Good agreement was obtained among the
      analytical results, the computer simulation, and the experimental data on time
      scales where the details of refractoriness are insignificant.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8136405
TI  - Rectification of correlation by a sigmoid nonlinearity.
AB  - We investigated the normalized autocovariance (correlation coefficient) function
      of the output of an erf() function nonlinearity subject to non-zero mean Gaussian
      noise input. When the sigmoid is wide compared to the input, or the input mean is
      close to the midpoint of the sigmoid, the output correlation coefficient function
      is very close to the input correlation coefficient function. When the noise mean
      and variance are such that there is a significant probability of operating in the
      saturation region and the sigmoid is not too flat, the correlation coefficient of
      the output function is less than that of the input. This difference is much
      greater when the correlation coefficient is negative than when it is positive.
      The sigmoid partially rectifies the correlation coefficient function. The
      analysis does not depend on the spectral properties of the input noise. All that
      is required is that the input at times t and (t + tau) be jointly gaussian with
      the same mean and autocovariance. The analysis therefore applies equally well to
      the case of two identical sigmoids with jointly gaussian inputs. This
      correlational rectification could help explain the parameter sensitivity of
      "neural network" models. If biological neurons share this property it could
      explain why few negative correlations between spike trains have been observed.

PMID- 8136406
TI  - Mathematical model for self-organization of direction columns in the primate
      middle temporal area.
AB  - We attempted to reproduce modular structures for direction selectivity
      characteristic of the primate middle temporal area (MT) based on our
      thermodynamic model for the activity-dependent self-organization of neural
      networks. We assumed that excitatory afferent input to MT neurons arises from V1
      and/or V2 neurons which are selective to both orientation of a visual stimulus
      and direction of its motion, and that such input is modifiable and becomes
      selectively connected through the process of self-organization. By contrast,
      local circuit connections within MT are unmodifiable and remain nonselectively
      connected (isotropic). The present simulations reproduced characteristic patterns
      of organization in the cortex of MT in that: (1) preferred directions of the
      afferent input gradually shifted, except for singularity lines where direction
      abruptly changed by 180 degrees; (2) model MT neurons located between the
      singularity lines responded to unidirectionally moving stimuli, closely
      reflecting preferred direction of the afferent input; (3) neurons responding to
      stimuli moving in two opposite directions were located along the singularity
      lines; and (4) neurons responding to stimuli moving in any direction were
      clustered at the ends of the singularity lines. When the strength of the lateral
      inhibition was decreased, direction selectivity of MT neurons was reduced.
      Therefore, the lateral inhibition, even if isotropic, strengthens the direction
      selectivity of MT neurons. Expression of singularities changed depending on a
      parameter that represents the relative dominance of the direction selectivity to
      the orientation selectivity of the afferent input.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8136407
TI  - "Velocity leakage" in the pigeon vestibulo-ocular reflex.
AB  - The transfer characteristics of the vestibulo-ocular reflex (VOR), and of the
      semicircular canal primary afferents (SCPAs) that drive it, have been studied in
      several species. In monkeys and cats, the dominant time constant describing
      horizontal VOR dynamics (tau hv) is longer than that (tau c) of horizontal SCPAs.
      This lengthening of the time constant has been attributed to a "velocity storage"
      mechanism that has been modeled as a positive feedback loop in the VOR pathways.
      We have studied the transfer characteristics of horizontal and vertical VOR and
      SCPAs in unanesthetized pigeons. In this species the dominant time constants of
      both the horizontal and vertical VOR (tau hv and tau vv) are shorter that tau c.
      This finding indicates that time constants characterizing the lower frequency
      response of the VOR can be lengthened or shortened depending on the species. We
      propose that in the pigeon the "velocity leakage" mechanism can be modeled by
      substituting negative feedback for positive feedback in the model of the VOR
      pathways. Negative feedback can also account for the further shortening of tau hv
      and tau vv as VOR gain increases with arousal. Additionally, making the negative
      feedback loop nonlinear can model the dependency of lower frequency VOR phase on
      amplitude, and skew in VOR waveforms. Pigeon VOR and SCPA dynamics also differ in
      their adaptive properties and higher frequency behavior. A predominance of input
      from highly adaptive SCPAs is proposed to account for the increased adaptation of
      the vertical VOR as compared with SCPAs overall. A pure time-delay associated
      with VOR operation can explain the phase lag of the VOR relative to SCPAs at
      higher frequencies.

PMID- 8136408
TI  - Stimulus sequence effects on human express saccades described by a Markov model.
AB  - Express saccades predominantly occur in experiments employing the gap paradigm
      where the target onset is separated from the fixation point offset by a blank
      period. Their relative frequency is distinctly influenced by catch trials (i.e.
      trials without a saccadic target) mixed into the stream of regular target trials.
      Generalizing this concept for other stimulus uncertainties (direction,
      amplitude), we found that the preparation time of a saccade depends on both the
      type of uncertainty used and the sequence of trial type (e.g., target vs catch,
      left vs right) in the experiment. This stimulus sequence effect is most prominent
      for catch trials. A similar but less pronounced effect can still be observed in
      the case of direction uncertainty but not in that of amplitude uncertainty. A two
      state Markov process model is proposed which is based on the dichotomy of express
      and regular saccades in the gap paradigm. According to this model the actual
      state of the saccadic system, which determines the type of saccade just in
      preparation, depends on the "trial history". The implications for models of
      saccade programming are discussed.

PMID- 8136409
TI  - Synaptic integration of NMDA and non-NMDA receptors in large neuronal network
      models solved by means of differential equations.
AB  - Alpha functions are commonly used to describe different receptor channel kinetics
      (non-NMDA, GABAA and GABAB). In this paper we show that they may be represented
      as solutions to simple ordinary differential equations. This alternative method
      is compared with the commonly used direct summation of the alpha function
      conductances in a high-level neuronal circuit model. A parametric study shows
      that the differential equation method greatly speeds up the previous summation
      method. The forward Euler method used to solve this differential equation is
      shown to be accurate for this type of simulation. The modelling of NMDA receptor
      channel kinetics is also discussed.

PMID- 8136410
TI  - Quantification of directional and orientational selectivities of visual neurons
      to moving stimuli.
AB  - Directional and orientational components usually coexist and are mixed in the
      cell's overall responses when moving optical stimuli are used to study the
      response characteristics of visual neurons. While these two properties were
      quantified with all the previous methods for data analysis, their effects could
      not be efficiently separated from each other, and thus the analyses were
      imperfect. In this paper, theoretical evidence and examples are provided to show
      the defects of the old methods. In order to separate the two components
      completely, we propose to apply optimal regression analysis with the sine-cosine
      function series as the fundamental variables. Based on this separation, we
      defined the orientational selectivity as variation of response strength with
      orientation and performed integration and averaging to quantify the two
      properties [cf. Eqs. (5) and (6)]. The present method has the advantages of
      completeness and accuracy, and can detect some details which would have been
      missed by other methods. An explanation of the intrinsic implications of the
      method and our comprehension of directional and orientational selectivities and
      preferred direction and orientation are also given.

PMID- 8136412
TI  - Carry-over biases in clinical pharmacology.
AB  - If the effect of a treatment carries on after the treatment is withdrawn then the
      response to a second treatment may well be due in part to the previous treatment.
      This so called carry-over effect may bias any clinical trial in which subjects
      are tested more than once. Cross-over studies can be routinely checked for this
      bias. In other study designs, however, common sense and alertness for unusual
      patterns in the data are the only defences against it. The amount of carry-over
      bias in clinical trials can be somewhat minimized by the following measures. Dose
      response studies, dose-titration studies, and open evaluation studies should
      require a sufficient washout period between the administrations of the drugs.
      Studies using duplicate standard deviations for the estimation of intra
      individual reproducibility of a test should routinely include a statistical test
      for differences between the duplicate data. Self-controlled studies should not be
      used otherwise than as an initial orientation for a new treatment. Parallel
      studies should routinely be stratified for symmetry of previous treatments.
      Studies with subjective variables are frequently influenced by psychological
      carry-over effects and should, therefore, be validated together with objective
      variables whenever possible.

PMID- 8136411
TI  - Neural network simulations of the primate oculomotor system. I. The vertical
      saccadic burst generator.
AB  - The performance of a neural network that simulates the vertical saccade
      generating portion of the primate brain is evaluated. Consistent with presently
      available anatomical evidence, the model makes use of an eye displacement signal
      for its feedback. Its major features include a simple mechanism for resetting its
      integrator at the end of each saccade, the ability to generate staircases of
      saccades in response to stimulation of the superior colliculus, and the ability
      to account for the monotonic relation between motor error and the instantaneous
      discharge of presaccadic neurons of the superior colliculus without placing the
      latter within the local feedback loop. Several experimentally testable
      predictions about the effects of stimulation or lesion of saccade-related areas
      of the primate brain are made on the basis of model output in response to
      "stimulation" or "lesion" of model elements.

PMID- 8136415
TI  - Laboratory assessment of five glucose meters designed for self-monitoring of
      blood glucose concentration.
AB  - We describe a laboratory assessment of five blood glucose meters. The
      instruments' analytical characteristics under optimum laboratory conditions and
      examination of potential sources of errors were intercompared. All glucometers
      produced precise results, and in all but one meter the CV values varied between
      1.5% and 6%. CV's for reproducibility and within-day precision of Glucometer Gx
      were 10.5% and 7.3%. Sample volume, blood incubation time and colour stability of
      the strip may influence the results of blood glucose measurements with glucose
      meters. Underloading the sample strip had statistically significant effects on
      normal blood glucose values for all meters. One Touch II gave also significantly
      different results when the strip was overloaded. Incubation times shorter or
      longer than those recommended by the manufacturer influenced the results of all
      glucose meters. After colour development of the strip, changes were small for
      Haemo-Glukotest 20-800R strips and Glucotrix, whereas Accutrend glucose strips
      had to be read immediately following the prescribed incubation time. Comparison
      of the glucose meter results with those obtained by the hexokinase method showed
      good correlation coefficients for Reflolux S (r = 0.992), Accutrend (r = 0.988),
      One Touch II (r = 0.942), Glucometer Gx (r = 0.986) and Glucocard (r = 0.976).
      Error grid analysis showed that the results of all meters were clinically
      correct. Variations in haematocrit are known to be a source of errors when blood
      glucose is determined with a test strip. In the normoglycaemic range the results
      obtained with Accutrend and Glucocard were not influenced by even extreme
      haematocrit values. In the high glucose concentration range there was a decrease
      in blood glucose values with increasing haematocrit for all meters. This error
      was smaller with Accutrend and Glucocard than with the other meters. Although the
      new versions of the monitors are easier to use, their analytical performance is
      not superior to earlier models.

PMID- 8136413
TI  - Alkaline phosphatase in human semen: an investigation using enzyme inhibitors and
      gel electrophoresis.
AB  - Human seminal alkaline phosphatase was investigated with respect to its
      electrophoretic mobility, heat lability, and susceptibility to inhibition by
      phenylalanine, tartrate, and homoarginine. Total alkaline phosphatase activity in
      30 samples of human semen was measured colorimetrically, using p
      nitrophenylphosphate as substrate. Using linear regression analysis, no
      significant correlation was found between the enzyme activity and the sperm
      count, sperm motility, semen volume, and the concentrations of seminal inositol
      and fructose. The alkaline phosphatase activity was higher in the earlier portion
      of split ejaculate samples. Sodium DL-tartrate (42 mmol/l), which inhibits acid
      phosphatase, did not inhibit seminal alkaline phosphatase significantly. L
      Homoarginine (10 mmol/l), an inhibitor of the liver and bone isoenzymes,
      inhibited the seminal enzyme (53%), whereas L-phenylalanine (12 mmol/l), a strong
      inhibitor of placental alkaline phosphate, decreased activity by about 10%.
      Electrophoresis of semen samples on agarose revealed a broad band which was not
      sharpened after treatment with neuraminidase. Semen total alkaline phosphatase
      was essentially totally inactivated by heating at 56 degrees C for 15 min or 10
      min at 65 degrees C; similar behaviour has been reported for the liver and bone
      isoenzymes. Electrophoresis after heating did not reveal a residual band of heat
      stable placental-like alkaline phosphatase. Semen alkaline phosphatase appears to
      contain more than one isoenzyme, but placental-like alkaline phosphatase cannot
      be more than a minor component.

PMID- 8136414
TI  - Prolactin heterogeneity: a limitation on the evaluation of results from prolactin
      assays due to differences in immunoassays and the different bioactivities of
      prolactin forms.
AB  - Prolactin exists in biological fluids in several molecular forms. This raises two
      questions: (1) whether the assay of prolactin by immunotechniques is valid and
      reliable and (2) whether the different forms have different physiological roles,
      which might be exploited to improve diagnostic accuracy and data interpretation
      by the use of appropriate methods. To investigate these questions, prolactin from
      human amniotic fluid was separated, by concanavalin A-Sepharose affinity
      chromatography, into bound, retarded and unbound fractions (bound prolactin
      fraction, retarded prolactin fraction, unbound prolactin fraction), which were
      characterized by electrophoresis, immunoblotting and glycan detection blot.
      Virtually no contamination was found in the bound prolactin fraction, and the
      unbound prolactin fraction and retarded prolactin fraction were 74-83% pure
      according to densitometry of the electrophoretic and immunoblot patterns. High
      variability was found among the individual patterns. Glycan detection in the
      blotted fractions revealed that the bound prolactin fraction bands corresponding
      to M(r)25,000-29,000 were weakly glycolysated, whereas the bands of M(r)60,000
      64,000 were significantly glycan-positive. Immunoreactive bands of unbound
      prolactin fraction and retarded prolactin fraction also stained positively for
      glycans. Using two commercial prolactin kits, the bound prolactin fraction forms
      were virtually undetectable. To demonstrate that the prolactin forms may depend
      on the hypothalamic state, two behaviourly different breeds of cattle were used
      as an animal model for studying hypothalamic activities. The number of
      immunoreactive bands, representing the prolactin forms, and the change of the
      forms in response to thyroliberin differed strikingly among the groups. The
      bioactivity of the forms was examined in bovine granulosa, oviductal, endometrial
      and spleen cells, and in murine splenocytes, the latter being activated by
      concanavalin A or allogeneically to create in vitro conditions that may have
      relevance for situations in vivo. The rate of incorporation of [3H]thymidine in
      murine splenocytes was dose-dependently enhanced only by bound prolactin
      fraction. The increase was abolished by purified anti-prolactin antiserum.
      However, the standard prolactin from the kits inhibited the proliferation even in
      low dose (1.25 microgram/l) and the inhibition was abolished in part by bound
      prolactin fraction. Thymidine incorporation into the bovine cells was
      significantly increased by low concentrations (2 micrograms/l) of unbound
      prolactin fraction and retarded prolactin fraction. Oviduct epithelial cells and
      splenocytes were stimulated by unbound prolactin fraction but not by retarded
      prolactin fraction in a dose of 16 micrograms/l. Thymidine incorporation into
      granulosa cells was inhibited by retarded prolactin fraction (16 micrograms/l)
      but not by unbound prolactin fraction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8136417
TI  - A European Quality Control Programme as a cooperative tool between users and a
      diagnostic company.
AB  - Achievement of appropriate precision is a major challenge for the clinical
      laboratory, particularly in specialized fields such as enzymology and
      immunochemistry. Especially in immunochemistry, where accuracy can only poorly be
      checked because of a lack of reference methods and a multitude of detectable
      epitopes, precision remains an important index of quality. In immunochemical
      methods there are three main sources of variation: differences in methodology,
      lot-to-lot variation and performance of the assay, the latter including the skill
      of the technicians and instrument performance. The results of a European Quality
      Control Programme for the users of one type of automated immunoassay analyser
      were compared with a similar Italian Quality Control Programme for users of
      different immunometric techniques. The precisions (%CV) of the two programmes
      were compared, as well as the number of values lying within one half of the
      biological variation of the analysed serum components. Feedback between users and
      manufacturers leads to a clear improvement in analysis performance, so that most
      of the considered values come to lie within the acceptable limits of 1/2 of the
      biological variation. It is concluded that both national and international
      quality control programmes are very useful for indicating the intrinsic quality
      of the quantities used in the clinical laboratory.

PMID- 8136416
TI  - Complex analyte-dependent and analyte-independent interferences with conjugated
      bilirubin in the enzymatic phenol-aminophenazone peroxidase (PAP) method for
      creatinine determination.
AB  - Although bilirubin interferes with the enzymatic assays for creatinine, neither a
      consensus of the degree of interference nor the mechanism has been established.
      Using multiple regression analysis, we demonstrate that the interference is
      negative and caused by both analyte-dependent and analyte-independent mechanisms.
      Furthermore, the correlative model includes terms non-linear with respect to
      creatinine. In the kinetic creatinine phenol-aminophenazone peroxidase method,
      there are analyte-dependent and analyte-independent mechanisms at work. The
      multivariate equation is: Crea' = 0.9879 Crea - 0.4524 Bili - 0.000828 Crea x
      Bili + 2.094 x 10(-7) Crea2 x Bili + 5.0 (Crea' = measured creatinine (mumol/l),
      Crea = true creatinine (mumol/l), and Bili = conjugated bilirubin (mumol/l)). The
      endpoint mode was affected less than the kinetic mode and exhibited different
      relationships in which two models describe the interference equally well. One is
      strictly analyte-dependent: Crea' = 0.9991 Crea - 0.00203 Crea x Bili + 2.390 x
      10(-6) Crea2 x Bili - 1.464 x 10(-9) Crea3 x Bili + 3.261 x Bili + 3.261 x 10(
      13) Crea4 x Bili - 9.9. The other is a complex combined analyte-dependent and
      analyte-independent: Crea' = 0.9834 Crea - 0.00680 Crea x Bili + 2.477 x 10(-7)
      Crea2 x Bili - 3.233 x 10(-7) Crea x Bili2 + 0.4652 Bili - 0.000458 Bili2 + 12.2.
      These models are valid for creatinine concentrations up to 2200 mumol/l (24.9
      mg/dl) and bilirubin up to 660 mumol/l (38.6 mg/dl). The interference increases
      with increments of either bilirubin or creatinine. In addition, we found that
      unconjugated bilirubin interferes differently from conjugated bilirubin in degree
      and mechanism. Model building, contour plots, surface plots, and possible
      mechanisms are discussed. We propose multiple regression analysis as the proper
      way to evaluate interferences because analyte-dependence can be easily missed by
      simple regression analysis. True creatinine concentrations can be estimated
      despite the interference from conjugated bilirubin. Other phenol-aminophenazone
      peroxidase methods may be similarly affected.

PMID- 8136418
TI  - Automated enzymatic methods for creatinine measurement with special attention to
      bilirubin interference.
AB  - Four enzymatic methods for creatinine measurement were evaluated on a DuPont
      Dimension automatic analyzer. Biomed Creatinine-Duo-UV (BIO) and Raichem
      Creatinine Reagent Enzymatic (RAI) start creatinine breakdown with creatinine
      iminohydrolase (EC 3.5.4.21) resulting in the formation of NH4+. The Boehringer
      Mannheim Creatinine PAP (BM1) and SopaChem Creatinine (SOP) start the breakdown
      of creatinine with creatininase (EC 3.5.2.10) which yields creatine. In order to
      reduce bilirubin interference, the BM1 method was modified to contain K4Fe(CN)6.
      This substance was added with reagent 1 (BM2) or with reagent 2 (BM3). All the
      enzymatic creatinine methods tested displayed good linearity for concentrations
      up to at least 1000 mumol/l. The BIO, BM3, RAI and SOP methods showed good
      stability of test outcome for the tested period of a week. The outcome of the BM1
      and BM2 method increased continually with time. Only the results of the RAI
      method were diminished by the presence of lipids. The BM1, BM2, BM3 and SOP
      methods showed no interference with haemoglobin, whereas this increased the
      outcome of the BIO method and slightly decreased the results of the RAI method.
      Using spiked human albumin solutions it was found that the BIO, BM2, BM3 and RAI
      methods displayed good resistance to interference by bilirubin or ditauro
      bilirubin. The outcome of the BM1 and SOP method was strongly decreased by both
      bilirubin and ditauro-bilirubin. When creatinine was measured in a panel of sera
      originating from 100 patients with bilirubin concentrations higher than 50
      mumol/l, the obtained results were in close agreement with those found for the
      spiked human albumin solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136419
TI  - Automated turbidimetry of serum lipoprotein(a).
AB  - We describe a simple immunoturbidimetric method for quantifying lipoprotein(a) in
      serum based on latex-enhanced particle agglutination technology. Carboxylated
      latex particles (diameter 240 nm) covalently coated with F(ab')2 fragments of
      anti-lipoprotein(a) antibodies are incubated with the sample for 5 min at 37
      degrees C, and the resulting agglutination is quantified by measuring the change
      of turbidity produced at 700 nm. The assay is rapid, precise and fully automated
      on the Hitachi 911 analyser. The assay range is about 0.03-0.9 g/l. Average
      analytical recovery was 97.8%. Precision (CV) ranged from 1.9 to 3.1% at
      different lipoprotein(a) values. There was no interference from bilirubin,
      Intralipid, haemoglobin, plasminogen or apolipoprotein B. Comparisons with a
      latex nephelometric assay carried out on the Behring nephelometer analyser, and
      with three commercially available methods, a radioimmunoassay and two ELISA
      assays, gave good correlations (r > 0.95), although a large among-method
      variation in lipoprotein(a) values was found. We conclude that the proposed latex
      turbidimetric immunoassay method is suitable for routine use in clinical
      laboratories.

PMID- 8136420
TI  - Multicentre evaluation of the Bayer DAX system.
AB  - The analytical performance of the DAX, a high-throughput random access analyser,
      was studied according to ECCLS guidelines (ECCLS Document Vol. 3, No. 2, Beuth
      Verlag, Berlin, 1986) in a multicentre evaluation involving four laboratories.
      The trial took about 4 months. Determinations of 12 analytes produced more than
      60,000 data. The imprecision study on 3 control sera for all analytes gave a
      within-run CV (median of 4 laboratories) which never exceeded 3% and was below 2%
      in 94% of the results. The median between-day CV was less than 3% in 92% of the
      results, with a highest value of 5.0%. No significant drift was detected during
      the 5-hour work period. No relevant sample- and cuvette-related carry-over was
      found. The manufacturer's claims concerning linearity were fulfilled or exceeded.
      The recovery of the assigned values for the control sera (median of 4
      laboratories) ranged from 94 to 106%. In the method comparison on patients'
      samples, deviations were statistically significant in some cases, due to
      differences either in the methods used or in the calibration of the systems used
      for comparison; the regression lines, as inspected visually, and the coefficients
      of correlation were, however, generally acceptable. Imprecision and inaccuracy
      were within the acceptability limits as recommended by the Societe Francaise de
      Biologie Clinique (SFBC) (Biochim. Clin. 12 (1988) 284-327) and the Deutsche
      Gesellschaft fur Klinische Chemie (DGKC) (Dt. Arztebl. 85 (11) (1988) A697-A712).
      The limits of acceptance, proposed more recently by Fraser et al. (Eur. J. Clin.
      Chem. Clin. Biochem. 30 (1992) 311-317), were met in thirty-three of thirty-six
      cases. The alpha-amylase assay was significantly affected by bilirubin and
      haemolysis; interferences for the remaining analytes were predictable and well
      known from the literature. The rate of sample throughput was found to be in
      agreement with that claimed by the manufacturer. The software did not present
      problems and was readily accepted by the operators. The practicability of the
      instrument was rated very good. Since the DAX is the primary chemistry analyzer
      in all four participating laboratories, the present experiments were necessarily
      intermixed with a large routine workload. Therefore, the system performance was
      assessed under definitely "usual" conditions. Because of its high productivity
      and reliability, the DAX is highly suitable for routine use in medium to large
      sized hospitals.

PMID- 8136421
TI  - Recommendation for the determination of the catalytic concentration of lactate
      dehydrogenase at 37 degrees C. Standardization Committee of the German Society
      for Clinical Chemistry, Enzyme Working Group of the German Society for Clinical
      Chemistry.

PMID- 8136422
TI  - [Infection in the diabetic foot].

PMID- 8136423
TI  - [Plasma insulin changes in obesity with or without abnormal glucose tolerance].
AB  - The aim of this study was to know about the plasmatic variations of insulin and
      its potential origin in the obesity with or without abnormal tolerance to
      glucose. Obese patients with normal tolerance to glucose showed normal and
      hypersecretion of insulin during fasting and after oral overdose of glucose
      (OOG). Fasting hyperinsulinism in patients with normal secretion of insulin was
      due to a decrease in its hepatic clearance, whereas in patients with
      hypersecretion, it was due mainly to insulin hypersecretion. Most of the obese
      patients with glucose intolerance showed hypersecretion of insulin during fasting
      and after OOG, being their basal hyperinsulinism due to insulinic secretion.
      After the OOG, the hyperinsulinism due to insulin hypersecretion and/or a
      decrease in its hepatic clearance. In addition, we observed an inverse
      correlation between body mass index and obese patients with normal tolerance to
      glucose.

PMID- 8136424
TI  - [Lipid profile in diabetic patients, according to changes in glucose control: a 2
      year study].
AB  - Disorders of the lipoprotein metabolism in diabetic patients are of great
      interest because their association to the presence of atheromatosis and because
      cardiovascular diseases are the major cause of mortality in diabetic patients.
      The aim of this study was to compare the lipidic scheme of our diabetic patients
      according to the type of diabetes, the age of onset and the evolution over the
      years, and to analyze the impact of variations in the glycemic control on such
      lipidic scheme. In the insulin-dependent diabetes mellitus, total cholesterol,
      LDL, HDL and triglycerides were within the recommended values for the age of the
      patients. There was a significant correlation between glycemia and HbAlc and
      triglycerides, total cholesterol and its LDL and HDL fractions. In non-insulin
      dependent diabetes mellitus, we observed average values of total cholesterol and
      LDL fraction higher than what is recommended for diabetic patients with the
      characteristics of this group. There was a significant correlation between basal
      glycemia, HbAlc and triglycerides, as in the insulin-dependent diabetes, although
      there was no correlation with total cholesterol and HDL. This absence of
      correlation may be due to the effect of other factors: age, inadequate dietary
      follow-up obesity and hyperinsulinism.

PMID- 8136425
TI  - [HLA DR7 as a protective factor against gold salt toxicity in rheumatoid
      arthritis].
AB  - We performed a study of antigens HLA type I and II (specificity DR) in 90
      patients with diagnosis of Rheumatoid Arthritis (RA) treated with Sodium
      Aurothiomalate (SATM) in order to detect the presence of an antigen HLA which
      could act as a protective factor against toxicity by SATM. Our results
      demonstrated a decrease in the frequency of the antigen DR7 in patients with
      toxicity by SATM, which suggests a protective factor of this antigen against the
      development of toxic reactions due to gold salts.

PMID- 8136426
TI  - [Thyroid nodule disease in a previously endemic goiter area].
AB  - We conducted a 6-year study of 110 patients with thyroid nodular disease in a
      previously goitrogenic area. The aim of the present work was to establish its
      incidence, to determine if multinodular goiter and autonomous thyroid nodule have
      the same analytical and clinical behaviour and to verify if the iodation campaign
      had resulted in the development of thyrotoxicosis induced by iodine. The results
      demonstrated an incidence of 0.4 per 1,000 population and per year. The two
      modalities of thyroid nodular disease did not present any clinical and analytical
      differences. 58.2% of the patients had hyperthyroidism, 53.1% of which were T-4
      thyrotoxicosis, 12.5% T-3 thyrotoxicosis and 34.4%, subclinical hyperthyroidism.
      8.2% of the patients under study had hyperthyroidism induced by iodine (Jod
      Basedow), with iodide excretion values higher that 3 standard deviations with
      respect to the population average (> 220 micrograms/g creatinine).

PMID- 8136427
TI  - [Local synthesis of immunoglobulins in neuropathies].
AB  - It is essential to know how the immune system acts in different neurological
      diseases, some of them non very well known or of unknown etiology at all. It was
      applied Reiber and Felgenhauer's formula in 56 patients with different diseases.
      IgA, IgM, IgG and albumin were quantified in sera and cerebrospinal fluid by
      simple immunodiffusion. It was observed more frequent IgG local synthesis and IgA
      in this sample.

PMID- 8136428
TI  - [Polyarthritis and hepatitis as presentation forms of secondary syphilis].
AB  - We present a luetic secondarism in a 40-year-old woman starting as symmetric
      polyarthritis and hepatitis. The latter presence of cutaneous rash, oral aphtae
      and anemia, as well as the positivity of anticore antibodies (1/160 core pattern)
      and anti-cardiolipin antibodies initially suggested a connectivopathy. The
      diagnosis of secondary syphilis was confirmed by the luetic seropositive results
      (RPR and FTAabs) and the microscopic observation of mobile microorganisms
      compatible with Treponemas in the exudate obtained by scraping of the cutaneous
      lesions. The proteiform expressivity of luetic secondarism is stressed, as well
      as its rare presentation with articular inflammatory manifestations.

PMID- 8136429
TI  - [Fever and recurrent bacteremia as presentation form of secondary aortoenteric
      fistula].
AB  - Secondary aortoenteric fistula is a rare complication, although very severe, of
      aortic revascularization surgery. The major cause is usually infection of the
      prosthetic material, which may happen short or long after the intervention. The
      most frequent forms of presentation are digestive hemorrhage, abdominal pain or
      unpleasantness, shock or other symptoms associated to the compression of adjacent
      structures. However, as in the present case, symptoms of systemic infection may
      be the only manifestation, with absence of local signs. This is why a high degree
      of clinical suspicion is needed. The most useful complementary techniques are
      computerized tomography, oral endoscopy and, probably, magnetic resonance, along
      with gammagraphy of indium-marked leukocytes. Therapy must combine long-term
      systemic antibiotherapy and resection of all infected material, with
      reconstruction of the vascular continuity following a route far away from the
      infected area.

PMID- 8136430
TI  - [Corynebacterium pseudodiphtheriticum pneumonia in a patient diagnosed with HIV
      infection].
AB  - Corynebacterium pseudodiphteriticum is a diphteromorphic bacterium, previously
      described as pathogenic in very few cases. We present the case of a patient
      diagnosed of infection by the human immunodeficiency virus (HIV), who developed
      pneumonia probably caused by Corynebacterium pseudodiphtheriticum and who had a
      good response to the initial empirical therapy with cephotaxime. We reviewed the
      literature on patients with diagnosis of HIV infection, acquired immunodeficiency
      syndrome (AIDS) and AIDS-related complex and we found just one case of this
      corynebacterium acting as pathogenic and causing a pulmonary abscess.

PMID- 8136431
TI  - [Idiopathic pulmonary hemosiderosis with good course in the adult: an atypical
      form?].
AB  - We present the cases of two adult patients hospitalized due to alveolar
      hemorrhage. In the absence of data regarding the affection of other organs and
      after a follow-up of 20 months and 4 years respectively, they were diagnosed as
      idiopathic pulmonary hemosiderosis (IPH). These patients represent two opposed
      extremes in the clinical spectrum of the disease, yet none of them needed therapy
      once they overcame the acute episode, remaining asymptomatic. Although the usual
      clinical course of IPH involves a short survival, given the evolution of our
      cases and of others previously described in the literature, one may think that at
      least a subgroup of adult patients have just one alveolar hemorrhagic episode as
      the result of the exposition to an unknown inhaled stimulus.

PMID- 8136432
TI  - [Acute ascites as the onset of mixed connective tissue disease].
AB  - We present a case of mixed disease of the connective tissue in a 37-year-old
      woman previously healthy, whose first manifestations were ascites, facial edemas
      and tibiomalleolars, latter progressing with constitutional syndrome, myalgias,
      Raynaud's phenomenon and esophagic disorders. In the literature reviewed, we have
      not found any other case of this type of onset in mixed disease of the connective
      tissue.

PMID- 8136433
TI  - [Impact of arterial hypertension on the central nervous system].
AB  - Cerebrovascular diseases (CVD) entail high costs associated to therapies,
      hospitalizations and disabilities. Arterial hypertension (AHT) is the major
      modifiable risk factor for the development of all types of CVDs (cerebrovascular
      accidents, vascular dementias, etc.). The increase of arterial pressure causes
      functional and anatomical changes in the cerebral circulation which facilitate
      the development of CVDs. The time of evolution and the severity of the AHT, as
      well as the associated vascular risk factors, will determine its impact on the
      central nervous system.

PMID- 8136434
TI  - [AIDS: towards a rationalization of its health care].
AB  - We review the current health care model for AIDS patients in local hospitals
      provided with few advanced technologies and a low level of research. We state
      arguments supporting the creation of Specialized Units for the treatment of these
      patients as the best way for the control, prevention and research of this new
      disease. We try to draw attention to a new problem which requires urgent
      solutions, in contrast with certain passive attitudes from the Authorities.

PMID- 8136435
TI  - [Carcinomatous meningitis as early manifestation of lung adenocarcinoma].

PMID- 8136436
TI  - [Recurrent spontaneous pneumomediastinum].

PMID- 8136437
TI  - [Pneumocystis carinii pneumonia simulating lung tuberculosis].

PMID- 8136438
TI  - [Chronic diarrhea caused by ticlopidine].

PMID- 8136439
TI  - [Medical responsibility in temporary work incapacity].

PMID- 8136440
TI  - [Hepatitis C in primary care: a study of carriers and their families].
AB  - OBJECTIVE: A clinical epidemiological study at a health centre of carriers of
      hepatitis C virus (HCV) antibodies. The prevalence of HCV antibodies in immediate
      family members. DESIGN: Crossover and descriptive. SETTING: Chopera I Primary
      Care team. PATIENTS AND FAMILY MEMBERS: 37 carriers of HCV antibodies in the
      Centre's records. 52 family members of 21 carriers. MEASUREMENTS AND MAIN
      RESULTS: A form containing the clinical and epidemiological data of each carrier
      was filled out. The diagnosis of HCV infection was made at the Health Centre in
      72.22% of cases. 80% evolved towards a chronic hepatitis. 56.75% had a history of
      parenteral transmission. 37.75% had no history of risk factors. The
      epidemiological data of the family members was recorded and transaminasaemia and
      the HCV antibodies were determined. Four cases (8.33%) with altered transaminase
      and three cases (6.82%) of positive antibodies were found. CONCLUSIONS: Existence
      of a high percentage of Hepatitis C of no known origin and a greater prevalence
      of carriers among family contacts than in the population as a whole. Essential
      role of Primary Care in the detection and follow-up of HCV carriers. A need for
      definitive studies on sexual transmission and the possible existence of other
      transmission routes. The setting-up of preventive measures against these routes.

PMID- 8136441
TI  - [The costs for a health center in relation to its activities].
AB  - OBJECTIVE: To establish a system of attributing costs of Health Centres (HC) in
      the Primary Care network in function of health care activity. DESIGN: Crossover
      study with a descriptive component. SETTING: Management. Primary Care. PATIENTS
      OR OTHER PARTICIPANTS: 22 Health Centres open during December 1991 within the
      Health Area. MEASUREMENTS AND MAIN RESULTS: Two groups for cost attribution per
      Health Centre were agreed: articles from Chapter II relating to health care
      activity and Pharmacy spending-->costs relating to activity (CRA); the remaining
      articles from Chapter II and Chapter I (staff payments)-->costs not relating to
      activity (CNRA). Costs relating to activity made up 62.51% of the total cost per
      HC (2.72% articles from Chapter II and 59.79% Pharmacy). The remaining 37.49%
      corresponded to costs not relating to activity (1.38% to the remaining articles
      from Chapter II and 36.11% to staff payments). CONCLUSIONS: We consider that the
      attribution of costs in function of the activity per HC is useful for the
      planning and management of Area resources and assists the application of
      efficiency criteria in Health Centres.

PMID- 8136442
TI  - [Self-aggressive behaviors in the emergency service].
AB  - OBJECTIVE: To discover the characteristics of self-damaging acts attended at a
      casualty department. DESIGN: Descriptive/retrospective study. SETTING: Hospital
      context. PATIENTS AND OTHER PARTICIPANTS: Those attended for damage to themselves
      in the Avila Hospital Casualty Department over a two-year period. MEASUREMENTS
      AND MAIN RESULTS: For the 62 cases surveyed, age, gender, source of referral, the
      method used, diagnosis, hour of arrival, length of time in the Department,
      destination on release and the seriousness of the act, were all evaluated. The
      most common method was taking drugs (72.6%). Among women (56.4%), emotional,
      personality and adaptive disorders predominated. Men (43.5%) were more commonly
      schizophrenic and showed abuse of/dependence on alcohol and drugs. They were also
      the most serious cases. 53.2% of cases required psychiatric admittance.
      CONCLUSIONS: Emotional disturbances and personality disorders were the most
      common cause of this type of behaviour.

PMID- 8136443
TI  - [The control of arterial hypertension in primary care: the evaluation of a
      program of self-care].
AB  - OBJECTIVE: To evaluate the efficacy of a self-care hypertension programme within
      primary care. DESIGN: Two models of intervention by means of self-care were
      compared, both using individual education and family support, with one of them
      using group education. SETTING AND PATIENTS: All those attending 10 health
      centres in Andalucia and who had a recent diagnosis of light or moderate
      Hypertension or with their hypertension not monitored over the preceding 6
      months, were included. MEASUREMENTS AND MAIN RESULTS: These 160 people were
      assigned at random to the intervention group (group education) or the control
      group (individual education). Data analysis provided the results for the 95
      people who completed the study. Both systolic and diastolic arterial pressure
      (SAP and DAP) diminished significantly during the study period, both in the
      sample as a whole and in the intervention group. However, the lessening of
      systolic pressure only reached statistically significant differences in the
      control group. Over the study period, the lessening of SAP was 6.2 in the
      intervention group and 8.0 in the control group; whereas the lessening of DAP was
      7.0 in the intervention group and 2.3 in the control group. CONCLUSIONS: Arterial
      hypertension can be controlled in primary care by health education for self-care.
      On the basis of this study's findings, it is not valid to conclude that group is
      more efficacious than individual education.

PMID- 8136444
TI  - [Brucellosis in the province of Almeria: a retrospective study of 1988-1990].
AB  - OBJECTIVE: To show the present spread of brucellosis in Almeria Province. DESIGN:
      Retrospective descriptive study. SETTING: Torrecardenas Hospital, Almeria.
      PATIENTS AND OTHER PARTICIPANTS: 137 cases of brucellosis diagnosed between 1988
      and 1990 in Almeria province. Study of individualised statements. MEASUREMENTS
      AND MAIN RESULTS: The incidence of brucellosis in Almeria was 0.25, 2.25 and 3.07
      times greater than that in the rest of the Spain during the years under study.
      70.80% of cases came from the rural environment. 70.80% were declared in the
      spring-summer months. 67.88% of patients were male. 7.29% were paediatric cases.
      42.31% belonged to a profession considered at risk. The means of infection was
      indirect in 46.71% of cases. The number of relapses was 10.21%. 3.64% were family
      cases. CONCLUSIONS: Brucellosis is endemic in the province of Almeria. The
      situation shows no sign of improvement, because the hygienic-sanitary controls
      covering both dairy products for consumption and those professionals at risk are
      deficient.

PMID- 8136445
TI  - [The seroepidemiology of the hepatitis A virus in children and adolescents].
AB  - OBJECTIVE: To know the prevalence of antibodies against hepatitis A virus (anti
      HAV) in a population of children and teenagers pertaining to three municipalities
      of the Autonomous Community of Madrid (CAM). DESIGN: Cross-study. SITE. The study
      was conducted in three public schools centers of the municipalities located in
      the Southeast of the (CAM). PATIENTS AND OTHER PARTICIPANTS: Students between the
      ages of 6 and 17 whose parents authorized them to be tested. MEASUREMENTS AND
      MAIN RESULTS: The presence of anti-HAV antibodies in the serum of 729 students
      was investigated. Thirty eight of them presented a positive mark, which indicates
      a prevalence of 5.34%. In the males, the prevalence was 5.7% and in the females
      it was 5%. CONCLUSIONS: The prevalence of anti-HAV antibodies is low in our
      population, agreeing with the delay in the age that the infection is acquired
      according to various publications.

PMID- 8136446
TI  - [Compliance with preventive activities at a primary care center].
AB  - OBJECTIVES: To evaluate the level of fulfillment of a number of prevention
      schemes carried out by the primary care team and to analyze the influence of some
      factors in the patients when fulfilling such schemes. DESIGN: Descriptive
      crossover study. SETTING: Primary Care. Health centre of Rekaldeberri, Bizkaia.
      PATIENTS AND OTHER PARTICIPANTS: 180 clinical records formed by patients from 14
      to 64 years old. MEASUREMENTS AND MAIN RESULTS: The percentage of clinical
      records in which the scheme carried out was correct was: blood pressure 57%,
      tobacco 41.1%, alcohol 24.5%, cholesterol 60%, height 32.8%, and weight 38.9%. A
      thorough study of the prevention scheme was carried out in patients who presented
      recorded pathology (high blood pressure and hypercholesterolemia). In some cases
      was recorded that there were some differences with regard to age and sex.
      CONCLUSIONS: We have to develop continuous training programmes in prevention
      schemes and revise the pattern of registration form, especially with regard to
      toxic habits.

PMID- 8136447
TI  - [Playing to save in the consulting room].

PMID- 8136448
TI  - [Cranial radiology in primary care].

PMID- 8136449
TI  - [Balint groups: a personal experience].

PMID- 8136450
TI  - [Gilbert's syndrome: the view from primary care].

PMID- 8136451
TI  - [The primary care tutor].

PMID- 8136452
TI  - [Hospital tutors and primary care tutors].

PMID- 8136453
TI  - [The exhaustive geriatric evaluation in primary care: an assessment of its
      utility].
AB  - OBJECTIVE: To describe the preliminary results from evaluating the application of
      an exhaustive geriatric evaluation procedure within primary care. DESIGN: A
      descriptive crossover study of a non-random sample. SETTING: This was carried out
      in primary care at an out-station clinic serving a suburban population. PATIENTS
      AND OTHER PARTICIPANTS: Those people aged 70 and over who requested health-care
      at the clinic. All the 131 people who attended between February and December 1992
      were included in the procedure. MEASUREMENTS AND MAIN RESULTS: The Exhaustive
      Geriatric Evaluation was applied as an instrument to diagnose hidden health
      problems. The instrument is composed of functional classification (Katz and
      Lawton-Brody scales), detection of risk factors which might lead to
      institutionalisation and an exhaustive clinical assessment (biomedical,
      psychological and socio-family). The diagnostic usefulness of the procedure is
      2.4 +/- 0.21 new diagnoses per patient, for 98% of those to whom the complete new
      procedure was applied (62.6% of the patients included). Problems of hypoacusis
      (33.3%), senile memory lapses (41.6%) and urinary incontinence (26.2%) were found
      to a significant degree (p < 0.05) compared with the previously diagnosed
      morbidity. On the Katz and Lawton-Brody scales, 74% and 41.9% of patients,
      respectively, were independent. 55.7% of patients presented at least one risk
      factor leading to institutionalisation, with loneliness being the most common
      (35.8% of cases). CONCLUSIONS: The exhaustive geriatric evaluation is valid in
      primary care in looking after the elderly population, as it leads to the
      detection of functional and hidden bio-psychosocial problems.

PMID- 8136454
TI  - Passive transfer of adjuvant-induced arthritis into irradiated DA recipient rats.
AB  - Adjuvant-induced arthritis (AIA) can be passively transferred in Dark Agouti (DA)
      rats by spleen and lymph node cells after culture with Concanavalin A (Con A). A
      model not requiring in vitro Con A expansion and activation would be important in
      investigations of anti-rheumatic drugs in AIA. A new model using irradiated
      recipients fills this need. Donor DA rats treated with 0.1 ml complete Freund's
      adjuvant (CFA) containing 7.5 mg M. butyricum/ml were sacrificed 11 days after
      CFA injection, donor spleen cells harvested, and donor spleen cells injected
      intravenously into recipient DA rats previously irradiated with 5 Gy. Recipient
      rats developed arthritis 4-14 days after spleen cell transfer. This model can now
      be used to further define the effects of anti-rheumatic drugs in the passive
      transfer of AIA by eliminating the need for the in vitro Con A-induced expansion
      and/or activation of donor cells.

PMID- 8136455
TI  - Expression of recombinant human thyroid peroxidase by the baculovirus system and
      its use in ELISA screening for diagnosis of autoimmune thyroid disease.
AB  - The cDNAs coding for human full-length and soluble thyroid peroxidase (TPO) were
      constructed, cloned into a baculovirus transfer vector and used for infection of
      Spodoptera frugiperda (Sf9) cells. The soluble TPO lacking 87 amino acids of the
      C-terminal transmembrane and intracisternal domains was designed as a fusion
      protein with a histidine-hexapeptide as an affinity ligand at its C-terminus.
      Whereas the recombinant full-length TPO was expressed mainly in an insoluble form
      in Sf9 cells, the recombinant soluble TPO was almost completely secreted into the
      culture medium. Both the full-length and the soluble TPO were purified by
      conventional methods and by a specific affinity chromatography using metal
      chelating matrix respectively, and tested for their autoantigenicity towards anti
      TPO autoantibodies. The ELISA established with the purified recombinant soluble
      TPO as antigen demonstrated its specificity, practicability and reproducibility
      in screening of anti-TPO autoantibodies in sera of autoimmune thyroid patients.
      High correlation (r = 0.89, n = 175) was obtained between the soluble TPO and
      natural TPO prepared from human thyroid glands. Pathological sera (n = 200) were
      positively assayed with a significance of 91%.

PMID- 8136457
TI  - CD8+ T cell tolerance and autoimmunity to extra-thymic antigens.

PMID- 8136456
TI  - Analysis of autoantibody reactivity in patients with Graves' disease using
      recombinant extracellular domain of the human thyrotropin receptor and synthetic
      peptides.
AB  - Graves' disease is characterized by hyperthyroidism leading to enhanced
      production of thyroid hormones. Hyperthyroidism is primarily mediated by the
      binding of autoantibodies to the thyrotropin receptor (TSHr). In the past, either
      thyroid cells or thyroid membranes were used as a source of TSHr to detect anti
      TSHr antibodies. Recently, we expressed the extracellular domain of the human
      TSHr (ETSHr) using the baculovirus expression system. In this study, we used
      ETSHr protein in an ELISA to detect anti-TSHr antibodies. Our data show that this
      assay can be used to analyze and quantitate isotype specific antibodies against
      the TSHr. To map immunogenic epitopes on the TSHr, we tested patients sera
      against synthetic peptides derived from two highly immunogenic regions (amino
      acid, AA 12-46 and 316-397) of the receptor. Although sera from patients with
      Graves' disease reacted with several peptides, they showed particularly strong
      reactivity against peptides from a relatively narrow region (i.e. AA 352-394) of
      the TSHr. The present study demonstrates the usefulness of the recombinant ETSHr
      to detect and characterize anti-TSHr antibodies in a simple and sensitive ELISA,
      and has lead to the identification of some of the immunoreactive epitopes on the
      TSHr.

PMID- 8136458
TI  - Lupus anticoagulant and monocyte procoagulant activity in polyabortive women.
AB  - Monocyte stimulation may be induced by various agents. Monocytes generate
      procoagulant activity (PCA) in response to stimulation; they widely interact with
      the hemostatic system and participate in thrombin formation. Extensive placental
      thrombotic infarction has been implicated in fetal death in polyabortive patients
      with lupus anticoagulant (LA). We investigated 38 polyabortive women: 17 LA
      negative (LA-) and 18 LA positive (LA+). We compared the results with 25
      clinically normal women. After four hours of incubation, the mean value of
      monocyte PCA in the LA+ women was significantly higher than in either the LA- or
      the control group (p < 0.0001). The monocyte PCA was out of the range of the
      controls in 9 of the 18 LA+ women. No correlation was observed between the levels
      of LA and monocyte PCA (r = 0.02; p = 0.94). No differences were found in
      monocyte PCA increase when induced by LA-, LA+ or control plasma; in all cases
      the increase was about five-six fold. Our results indicate that an increased
      monocyte PCA is present in some LA+ polyabortive women, thus suggesting that
      monocyte activation might be involved in the formation of thrombotic placental
      infarction and the consequent fetal loss in some patients. It might also suggest
      that these patients, in particular, could benefit from corticosteroid treatment,
      which is known to inhibit the formation of monocyte PCA.

PMID- 8136459
TI  - Non-restricted immunoglobulin-G subclass islet cell antibodies in Chinese.
AB  - Islet cell antibodies (ICAs) in Chinese (23 IDDM, 13 NIDDM and 6 non-diabetic)
      were characterized for immunoglobulin isotypes and light chain specificity. All
      ICAs were IgG-type and none were IgM- or IgA-type (median titre: 20 JDF units;
      range 10-160). Light chain specificity showed that 25/36 (69.4%) of the diabetic
      patients had lambda and kappa chains. Half of the non-diabetic subjects had both
      lambda and kappa chains. The rest had only lambda chains. Isotyping for ICA-IgG
      subclass combination with IUIS/WHO reference monoclonal antibodies in the
      diabetic patients gave the following: IgG1 alone-9 (25%), IgG1+2+3-8 (22.2%),
      IgG1+2-11 (30.6%), IgG1+3-6 (16.7%), IgG2+3-2 (5.6%). No ICA-IgG4 was detected.
      The frequency of the subclasses would be: IgG1-94.4%, IgG2-58.3% and IgG3-44.4%.
      The distribution of ICA-IgG subclasses was not affected by diabetes type (IDDM or
      NIDDM) or duration of disease. Of the 6 non-diabetic subjects only one had a
      single ICA-IgG subclass (IgG1). Serum levels of IgG subclasses in a subgroup of
      the patients (n = 16) were not significantly different from normal individuals.
      Biochemical modification of pancreatic tissue prior to ICA testing showed that
      acetylneuraminic acid residues, lipid and protein components were associated with
      binding of ICAs. The co-existence of other autoantibodies was also tested in
      these 42 ICA-positive sera. Twelve individuals (1 non-diabetic) had thyroid
      autoantibodies. Antibodies to thyrotrophin receptor, gastric parietal cell and
      rheumatoid factor were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136460
TI  - Aminoguanidine, an inhibitor of nitric oxide formation, fails to protect against
      insulitis and hyperglycemia induced by multiple low dose streptozotocin
      injections in mice.
AB  - It has been suggested that pancreatic beta-cell destruction occurring during the
      process leading to insulin-dependent diabetes mellitus (IDDM) involves formation
      of nitric oxide (NO). We have presently studied the effect of aminoguanidine
      (AG), which has recently been reported to inhibit generation of NO induced by the
      cytokine interleukin-1 beta. AG currently counteracted IL-1 beta induced
      impairment of the glucose oxidation rate in rat pancreatic islets. Then we
      studied the effect of AG on the development of hyperglycemia and pancreatic
      insulitis in mice treated with multiple low dose injections of streptozotocin (40
      mg/kg body-weight for five consecutive days). It was found that one daily
      intraperitoneal injection of AG (50 mg/kg body-weight) for 14 days failed to
      prevent the development of diabetes as well as insulitis following the
      streptozotocin injections. Furthermore, the mice treated with streptozotocin plus
      AG showed an increased mortality compared to mice treated with streptozotocin
      plus saline. Although the present data do not exclude a role for NO in IDDM, it
      raises concerns about the use of testing AG as therapeutic agent in IDDM.

PMID- 8136461
TI  - Interleukin 8.

PMID- 8136462
TI  - Experimental autoimmune pinealitis in the rat: ultrastructure and quantitative
      immunocytochemical characterization of mononuclear infiltrate and MHC class II
      expression.
AB  - Lewis rats immunized with Peptide M (an oligopeptide epitope of the S-antigen
      protein) developed experimental autoimmune uveoretinitis (EAU) and experimental
      autoimmune pinealitis (EAP). Temporal changes in mononuclear infiltrate to the
      pineal gland were quantitated by computer image analysis of sections
      immunostained with monoclonal antibodies to specific mononuclear populations. T
      helper/inducer cells (W3/25+) and monocyte/macrophages (OX-42+) were elevated
      during the early phases of inflammation (day 15) while cytotoxic/suppressor T
      cells (OX-8+) were elevated at days 15 and 21. Expression of MHC class II (OX-6)
      was markedly enhanced on pineal glia, but was not present on vascular endothelia
      during EAP. Ultrastructurally, many capillaries exhibited thickenings of the
      endothelia and basal lamina. EAP had little effect on the fine structure of
      pinealocytes and glia and there was little evidence of cellular destruction by
      day 21, in contrast to the extensive retinal destruction resulting from EAU.
      These findings suggest fundamental differences between EAU and EAP related to
      mechanisms of antigen processing/recognition in autoimmune diseases. Our study
      further indicates the importance of EAP as a model to investigate neuroendocrine
      immune interactions.

PMID- 8136464
TI  - Susceptibility and resistance to cyclosporin A-induced autoimmunity in rats.
AB  - Lethally irradiated Lewis (LEW) rats, reconstituted with syngeneic bone marrow
      and next given Cyclosporin A (CyA) for several weeks, develop disease
      (Cyclosporin A-induced autoimmunity; CyA-AI) after withdrawal of CyA. This
      disease resembles in terms of dermal changes the acute dermatitis and chronic
      scleroderma also seen in graft-versus-host disease (GVHD). In this study we
      report the relative resistance of the Brown Norway (BN) rat strain to the
      induction of CyA-AI. In contrast to LEW rats, in which CyA-AI was originally
      described, BN rats showed no acute dermatitis or scleroderma-like skin pathology
      in spite of comparable changes in the thymus and a maturation arrest of CD4+ T
      cells. The difference was also demonstrated functionally for whereas in LEW rats
      delayed-type hypersensitivity (DTH) reactions could not be elicited during CyA
      AI, these were within normal limits in BN rats subjected to the same protocol; NK
      activity on the other hand was unaffected in both strains. The observation that
      BN rats developed very mild late disease as evidenced by a slight though
      significant weight loss suggests that the BN strain is susceptible to the disease
      but that lesser effector cell generation or, alternatively, stronger suppressor
      cell responses may prevent dermal disease. These observations may contribute to
      the elucidation of the mechanisms involved in this experimental autoimmune
      disease.

PMID- 8136463
TI  - Autoantibodies to phospholipids and brain extract in patients with the Guillain
      Barre syndrome: cross-reactive or pathogenic?
AB  - Guillain-Barre syndrome (GBS) is a transient neurological disorder characterized
      by an inflammatory demyelination of peripheral nerves. Although the pathogenesis
      of GBS has not been elucidated, there is increasing evidence pointing to an
      autoimmune etiology. We have studied the reactivity of GBS sera with various
      phospholipids which are known to be important constituents of myelin, and serve
      as autoantigens in other autoimmune conditions. Sixteen Guillain-Barre syndrome
      (GBS) sera were studied for the presence of autoantibodies to ssDNA, dsDNA,
      cardiolipin (CL), phosphatidyl-ethanolamine (PE), phosphatidyl-choline (PC),
      phosphatidyl-serine (PS), and brain extract. Six of the 16 GBS sera had
      autoantibodies to one or more of the antigens studied. Three of the sera
      contained autoantibodies to brain extract (p < 0.05), two of the sera had
      autoantibodies to dsDNA, ssDNA, CL and PE, and one serum had autoantibodies to
      PC, and PS. As expected a significant proportion of the lupus sera contained
      autoantibodies to ssDNA and dsDNA, while the frequency of autoantibodies to
      different phospholipids was significantly high in sera of patients with systemic
      lupus erythematosus (SLE) and cerebritis. Absorption of GBS sera with
      cardiolipin, phosphatidyl-choline, or brain extract inhibited the binding of the
      sera to cardiolipin. Our results demonstrate that some GBS patients produce
      autoantibodies to various phospholipid and nuclear antigens. However, these
      autoantibodies are probably produced as a result of the myelin damage rather than
      cause the demyelination.

PMID- 8136465
TI  - Aberrant cellular localization of rubella viral genome in patients with adult
      Still's disease--a pilot study.
AB  - The rubella virus (RV) genome was detected using polymerase chain amplification
      techniques in several peripheral blood cell populations in patients with adult
      Still's disease (ASD) and normal controls (NC), including mononuclear cells
      (PBMC), B-cells, T-cells, monocyte/macrophages, and polymorphonuclear leukocytes
      (PMN). Five of 6 ASD patients and 3 of 6 NC subjects had detectable RV genome.
      Viral genomic load was significantly higher in ASD than in NC subjects (4.4 fold
      higher, p = 0.03). Interestingly, a differential cellular distribution of viral
      genome was observed between ASD and NC individuals. RV genome was detected more
      frequently in the PBMCs of ASD (5 of 6) patients compared to 2 of 6 NC. The viral
      genome was more localized to the PMN compartment equally in ASD and in NC
      subjects. On further cellular analysis, RV genome was detected in B-cells and
      macrophages but not T-cells in one patient. Existence of a differential viral
      genomic reservoir between ASD and NC suggests that this may play a role in the
      pathogenesis of disease manifestations and may reflect the inability to clear
      latent virus.

PMID- 8136466
TI  - Hormones in self tolerance and autoimmunity: a role in the pathogenesis of
      rheumatoid arthritis?
AB  - Recent studies indicate that pituitary hormones play an important role in
      immunoregulation. The evidence that endocrine abnormalities are associated with,
      and may contribute to the development of autoimmune disease is reviewed and
      discussed. Patients suffering from rheumatoid arthritis show a number of
      endocrine abnormalities that indicate altered pituitary function. The decreased
      bioactivity of prolactin and possible inadequate glucocorticoid response to
      inflammation found in patients may have an etiological role in rheumatoid
      arthritis. The further clarification of the possible role of endocrine factors in
      the etiology of autoimmune disease is needed urgently.

PMID- 8136467
TI  - Factors governing the binding and recognition of foreign and self-peptides by MHC
      class II.
AB  - Considerable progress has been made in understanding the basis of T cell
      recognition and T cell activation. This knowledge has recently been used to
      modulate T cell activation in animal models of experimental autoimmune disease by
      two means--selective MHC blockade and peptide-induced tolerance. The use of
      peptides to interfere with the binding of autoantigenic peptides to MHC requires
      knowledge of both the class II allele which presents the immunodominant peptide
      to autoimmune T cells and the identification of peptide analogs that bind with
      high affinity to that allele. The alternative strategy of peptide-induced
      tolerance will require identification of the autoantigen and its immunodominant
      peptides. While the latter approach holds great promise for immunointervention,
      its wide application will require full knowledge of the mechanisms by which
      tolerance to self is maintained and how it can be broken.

PMID- 8136469
TI  - [The radiation risk between facts and assumptions].

PMID- 8136468
TI  - The role of adhesion molecules in the pathogenesis of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      infiltration of mononuclear cells, mainly T lymphocytes, into the synovial
      membrane (SM). The interaction of peripheral blood T cells with the different
      components of the rheumatoid synovium is mediated by cell surface proteins such
      as selectins, integrins, members of the immunoglobulin superfamily and homing
      receptors. T lymphocytes infiltrating the rheumatoid SM show an activated
      phenotype and display an increased avidity of their adhesion receptors that
      results in an enhanced interaction of these cells with both extracellular matrix
      proteins (ECM) and cellular ligands (VCAM-1, ICAMs). The interaction of T cell
      integrins with their ligands, besides an additional antigenic stimulus, could
      trigger a mitogenic response on these cells, a phenomenon that can contribute to
      increased cellularity observed into the rheumatoid SM. Moreover, cell attachment
      to ECM through integrins induces the secretion of several proteases that can
      contribute to the tissue damage observed in RA. The increased knowledge about the
      role of adhesion receptors in the pathogenesis of RA and other inflammatory
      diseases will allow the introduction of a new therapeutic approach by: the use of
      specific blocking reagents designed to interfere with the function of adhesion
      molecules.

PMID- 8136470
TI  - [Mammography 1994, II. The new tasks of mammography].

PMID- 8136471
TI  - [The role of MRT in detecting the cause of therapy-refractory partial complex
      epilepsy].
AB  - MRT is of considerable significance in the investigation of epilepsy because of
      its ability to render soft tissue contrast for the demonstration of structural
      lesions. The present retrospective study consists of an analysis of MRT findings
      in operatively confirmed, circumscribed temporal tumours and in hippocampal
      sclerosis. The examinations were performed under standard conditions using T1-
      and T2-weighted spin-echo sequences of the head and coronal T2-weighted gradient
      echo sequences of the brain stem. The diagnosis of tumours was extremely accurate
      (22/23) and specific (18/23) whereas hippocampal sclerosis could not be
      satisfactorily demonstrated (5/18). The use of intravenous contrast medium did
      not provide any advantages.

PMID- 8136472
TI  - [Cerebral aneurysms: their 3-dimensional imaging with spiral CT].
AB  - In this study, the possibility of non-invasive, three-dimensional demonstration
      of aneurysms of the basal cerebral arteries by means of spiral CT was
      investigated. The first step was to obtain exact definition of optimal
      examination parameters. Angio CTs at appropriate levels were performed on 10
      subjects and time/density curves of the arterial and venous phases obtained in
      order to optimise the beginning of the arterial spiral CT series. The second step
      in this investigation was to examine 7 patients; in 6 of these basal aneurysms
      had been demonstrated by DSA. By means of multiplanar three-dimensional
      reconstruction from the data of the spiral CT it was possible to demonstrate 7
      aneurysms with a diameter between 5 and 18 mm. Their position and relationship to
      the bony skull was also shown.

PMID- 8136473
TI  - [The value of MR tomography after transsphenoidal hypophyseal resection. A
      retrospective comparison between endocrinology, operation and MRT].
AB  - Postoperative magnetic resonance images of 40 patients after transsphenoidal
      surgery for pituitary adenoma were evaluated retrospectively. The signal
      intensities of packing material and residual tumour were analysed. T1-weighted
      spin-echo sequences were obtained in coronal and sagittal views with and without
      intravenous injection of contrast media. Residual tumour demonstrated homogeneous
      or inhomogeneous signal intensity on the native scan with homogeneous or
      inhomogeneous enhancement. Packing material demonstrated a homogeneous signal
      intensity on the images obtained without injection of contrast media with a
      peripheral enhancement or alternate layers of low and intermediate signal
      intensity with alternate enhancement after injection of contrast media. In 5 of
      54 examinations different results were found in MRI, endocrinology and surgery
      (two false negative and one false positive MRI in correlation with endocrinology;
      two residual tumours on MRI where surgery was supposed to be complete).
      Application of intravenous contrast media facilitates the interpretation of
      postoperative examination of the pituitary gland as well as comparison with
      preoperative examinations and the knowledge of the intraoperative procedure.

PMID- 8136474
TI  - [Gadolinium-DTPA (Magnevist) as contrast medium for arterial DSA].
AB  - 16 DSA investigations using intra-arterial Gd-DTPA were performed on 12 patients.
      The contrast medium was administered either as a 0.5 molar gadolinium solution
      (commercially available) or diluted with distilled water to a 0.2-0.4 molar
      gadolinium solution. The injection was made either by pressure injector or by
      hand. The aortic arch, abdominal aorta and pelvic and lower limb arteries were
      examined. 14 of the 16 procedures were diagnostically adequate, but compared with
      iodinated contrast materials, contrast was less marked. There were no
      cardiovascular, neurological or allergic side effects. Three patients suffered a
      feeling of heat and one patient had mild pain during the injection. Even large
      volumes rapidly injected (up to 20 ml/s of the commercially available solution)
      were well tolerated. DSA with intra-arterial Gd-DTPA seems to be a suitable
      alternative for vascular imaging if iodine-containing contrast materials are
      contraindicated.

PMID- 8136475
TI  - [Transvenous sonography of the peripheral arterial vessels. The initial clinical
      results].
AB  - Intravascular ultrasound with 20 MHz/6.2-French transducer systems was used for
      arterial imaging via a transvenous approach. In 20 patients suffering from
      chronic arterial occlusive disease, 15 iliac arteries were evaluated during
      diagnostic angiography and 5 femoropopliteal arteries during balloon angioplasty
      (n = 3) and laser-assisted angioplasty (n = 2), respectively. Transvenous
      sonography did not allow differentiation of arterial wall layers and
      determination of vessel diameters as is usually possible during intraarterial
      sonography. Visualisation of iliac arteries was incomplete. In femoropopliteal
      vessels, guide wires could be detected within the arterial lumen but not in
      complete occlusions. Delivery of pulsed laser energy induced bright echoes near
      the catheter tip within a distance of 1-2 cm. Transvenous sonography is
      insufficient for monitoring of peripheral angioplasty; however, improved imaging
      quality might be possible at lower frequencies.

PMID- 8136476
TI  - [The determination of the normal values of blood flow velocities in the superior
      mesenteric artery of premature and term newborns with duplex sonography].
AB  - In a prospective study blood flow velocity measurements were performed in 110
      "healthy" newborn with duplex Doppler sonography in the superior mesenteric
      artery to obtain standard values. In 49 of these neonates 15, 30, and 45 minutes
      following feeding examinations were performed. Peak systolic flow velocity, end
      systolic flow velocity, time average flow velocity and time average maximum flow
      velocity were determined, the resistance and Pourcelot index as well as the
      volume blood flow were calculated. The children's gestational age was 27-42
      weeks, the postnatal age was 2-68 days and the body weight was 920-4190 g. All
      measured blood flow velocities showed a synchronous relation to feeding with an
      increase of blood flow velocity between 15 and 30 minutes and a decrease of blood
      flow velocity after feeding. The ascertained fasting measurements from 91 newborn
      (last feeding > 3 h < 12 h) differed significantly from the ascertained basic
      fasting measurements (last feeding > 12 h) from 15 infants.

PMID- 8136477
TI  - [Fat-suppressed MR imaging sequences in the diagnosis of liver and pancreatic
      neoplasms at 1.5 tesla].
AB  - We investigated 55 patients with suspected neoplasms of the liver and/or pancreas
      using fat-suppressed spin echo and gradient echo MR sequences. T1 and T2 weighted
      fat-suppressed spin echo sequences provided higher sensitivity for the detection
      of liver metastases. In the diagnosis of pancreatic tumours, T1 weighted fat
      suppressed gradient echo sequences after application of intravenous and oral
      paramagnetic contrast agents offered more information than other sequences.
      Drawbacks of fat-suppressed sequences are an increase in scan time and
      inhomogeneous fat-suppression at the periphery of the image.

PMID- 8136478
TI  - [Computed tomography of the kidneys following tumor enucleation].
AB  - Two weeks to 120 months after enucleation of renal tumours the postoperative
      defects were correctly localized by renal computed tomography in 34 patients.
      Typical defect morphology was either wedge-shaped or concave. No dependence on
      tumour localization, tumour size, operative technique or a certain surgeon was
      observed. The cortical defects were smaller (mean 2.0 cm) than the original,
      prominent tumours (mean 3.4 cm). In small defects without tension suture of the
      capsule is sufficient, leading to minor defects. Larger defects were closed with
      a retroperitoneal or free peritoneal fat flap resulting in larger residual
      defects. In case of intra- or postoperative bleeding, CT could demonstrate
      parenchymatous or perirenal haematomas or delayed perfusion of adjacent
      parenchyma. In one patient a recurrent tumour was correctly diagnosed, different
      postoperative complications (such as abscesses) were not observed.

PMID- 8136479
TI  - [Quality control for localized in-vivo proton spectroscopy on clinical MR
      equipment].
AB  - The localisation techniques STEAM and PRESS using echo times of 135 ms were
      tested for their performance. The selection parameters selection efficiency,
      contamination and outer volume suppression factor were determined as well as the
      quality of water suppression and the linearity of signal intensities versus
      concentrations. Using a voxel size of 2 x 2 x 2 cm3 PRESS localisation showed
      better values for the selection parameters than STEAM: selection efficiency: 6.0
      vs. 4.6%, contamination: 0.70 vs. 3.26%, outer volume suppression factor: 220,000
      vs. 60,000. Signal intensities showed good linearity (r2 = 0.9996) with
      concentrations of more than 10 mM, but below that concentration deviation of more
      than 10% should be taken into account. Measurements for quality assessment are
      important to optimise measurement protocols and for estimating the clinical value
      of in vivo measurements.

PMID- 8136480
TI  - [The quantitative determination of bone mineral content--a system comparison of
      similarly built computed tomographs].
AB  - An intercomparison of 4 CT scanners of the same manufacturer was performed. The
      bone mineral content of 11 lumbar vertebral columns removed directly post mortem
      was determined in a specially constructed lucite-water phantom. Even devices of
      the same construction were shown to yield a variation in the quantitative
      evaluation markedly exceeding the annual physiological mineral loss. As long as
      scanner adjustment by physical calibration phantoms has not yet been established,
      a course assessment and therapy control of bone mineral content should always be
      carried out on the same QCT scanner.

PMID- 8136481
TI  - [The value of the InSight HC asymmetric film-screen system in thoracic
      diagnosis].
AB  - The asymmetric film-screen system InSight HC represents a development to optimize
      chest imaging. The purpose of the study was to compare the exposure range and the
      image quality of this new system with a conventional film-screen system. The
      optical density of images in both techniques was measured and the image quality
      of 100 chest images from 50 intensive-care patients was evaluated. 4 observers
      graded the image quality of organic, non-organic and pathological structures.
      Statistical evaluation was performed by interobserver analysis. The asymmetric
      film-screen system shows a larger exposure range and a superior image quality in
      the mediastinal field. The image quality in the peripheral field must be judged
      critically and improved especially because of the poor recognizability of
      pneumothoraces.

PMID- 8136482
TI  - [A splenic hamartoma with clinical symptoms].

PMID- 8136484
TI  - [Marked mesenteric neurofibromatosis in neurofibromatosis 1].

PMID- 8136483
TI  - [The metastases of an occult bronchial carcinoma in a transplanted kidney. A case
      report on the differential diagnosis of multiple space-occupying lesions in a
      transplanted kidney].

PMID- 8136485
TI  - [Hypoplasia and stenosis of the A. carotis interna in a case of Sturge-Weber
      syndrome].

PMID- 8136486
TI  - [Apropos of the article by S. Kosling et al.: Rhabdomyosarcoma of the heart with
      unusual spread. Fortschr. Rontgenstr. 158 (1993) 180-182].

PMID- 8136487
TI  - Technology transfer to the developing world: does new technology have any
      relevance for developing countries?
AB  - Technology is not limited to equipment and commodities but includes know-how,
      understanding and the ability to control and exploit underlying principles and
      processes. Diverse technologies, not only those termed 'biomedical', affect the
      incidence and control of all diseases including tuberculosis. 'New technology'
      implies something recently developed, but any technology is new to those without
      prior experience. For developing countries, technologic novelty is far less
      important than relevance, which encompasses, among other things: direct
      application to reducing risk of infection and disease; affordability and cost
      effectiveness; saving foreign exchange; satisfying public demand with political
      benefit to the government; and promotion of social equity. The value of health
      gained by the new technology should exceed its cost, but this is difficult to
      measure. It is usually presumed that industrial countries are eager to export
      technologies, but intellectual property and patient regulations of the importing
      country may inhibit such transfers. Similarly, ethical issues involving
      protection of human subjects and informed consent may complicate clinical trials
      and technology assessment in the developing country environment.

PMID- 8136488
TI  - Lung diseases in the tropics. Part 2: Common tropical lung diseases: diagnosis
      and management.
AB  - This is the second of the two articles discussing clinical features, radiographic
      abnormalities, laboratory tests, pathogenesis and therapy of common tropical
      disorders affecting the lungs. We have arbitrarily selected the diseases, which
      are worldwide in distribution and demand urgency in addressing the problems of
      morbidity and mortality. The tropical physician is often reduced to administering
      pills, capsules or liquids. Our aim is to provide succinct and clear descriptions
      combining scientific information with common sense clinical wisdom.

PMID- 8136489
TI  - Sensitivity to sensitins and tuberculin in Swedish children. Part 5: A study of
      school children in an inland rural area.
AB  - SETTING: Since 1986 we have tested approximately 7000 non-BCG-vaccinated Swedish
      children with tuberculin and with Mycobacterium avium or M. scrofulaceum
      sensitin. In Goteborg, an urban coastal area, 25% of 8-9-year-old school children
      reacted to M. avium sensitin and 32% of M. scrofulaceum sensitin using a 6 mm cut
      off. OBJECTIVE: To evaluate if geographical factors have an influence on the
      prevalence of children reacting to tuberculin and sensitins. DESIGN: 2000
      schoolchildren of the same age as those in Goteborg but living in an inland rural
      area were Mantoux-tested in a similar way (simultaneously on separate arms with
      PPD RT23 and either of the two sensitins). RESULTS: 15% reacted to PPD RT23, 9.7%
      to M. avium and 13.9% to M. scrofulaceum sensitin. None of the children with a
      PPD RT23 reaction > = 6 mm showed signs of tuberculosis or had any known
      exposure. A reaction to PPD RT23 was usually combined with a still larger
      sensitin reaction. CONCLUSION: There was a considerable geographic difference in
      sensitin reactivity, low in an inland rural area compared to a coastal urban
      area. Children reacting to PPD RT23 had probably not been infected by M.
      tuberculosis but more likely by atypical mycobacteria. The reactions should be
      interpreted as cross-reactions.

PMID- 8136490
TI  - A case control study on human immunodeficiency virus-1 (HIV-1) infection as a
      risk factor for tuberculosis and leprosy in western Kenya.
AB  - A case control study was undertaken in Western Kenya from April 1989 to August
      1990 to evaluate HIV-1 infection as a risk factor for tuberculosis and leprosy.
      The study involved 144 newly diagnosed sputum smear positive tuberculosis cases
      with 432 age, sex and neighbourhood-matched controls, and 132 diagnosed leprosy
      cases with 384 matched controls. Odds ratios obtained by conditional logistic
      regression (matched) analysis were 4.9 (95% CI 2.6, 6.8), and 1.8 (95% CI 0.9,
      3.2), for the association between HIV-1 and tuberculosis and leprosy
      respectively. Approximately 31% of tuberculosis cases among males, and 11% of
      cases among females, were attributable to HIV infection.

PMID- 8136491
TI  - Immunological evaluation of a 12-kilodalton protein of Mycobacterium tuberculosis
      by enzyme-linked immunosorbent assay.
AB  - OBJECTIVE: To purify and study the seroreactivity of native and recombinant 12
      kilodalton protein of Mycobacterium tuberculosis H37Rv. DESIGN: M. tuberculosis
      H37Rv cells and Escherichia coli XL-1 containing the plasmid PRL4 encoding the M.
      tuberculosis heat shock protein GroES homolog were used as sources for the
      purification of native and recombinant 12 kD of M. tuberculosis respectively. The
      seroreactivity of the 12 kDs was studied by ELISA using sera from 35 leprosy and
      25 active pulmonary tuberculosis (TB) patients, and from 10 normal healthy
      controls. RESULTS: The 12 kD protein was purified from H37Rv extract (s12 kD) and
      from recombinant E. coli (r12 kD) by ultrafiltration and MonoQ fast pressure
      liquid chromatography (FPLC). Analysis of s12 kD and r12 kD by SDS-PAGE revealed
      a single protein band in both cases with an approximate molecular weight of
      12,000 which was recognized by monoclonal antibody SA-12 in immunoblotting. Both
      the proteins exhibited a pI of approximately 4.6 by isoelectric focusing. Both
      the 12 kD proteins exhibited 96% positivity with TB sera as compared to normal
      control sera (P < 0.01). Only one serum sample from the 35 leprosy sera tested
      exhibited binding to both the s12 kD and r12 kD proteins. Delayed type
      hypersensitivity reaction to the 12 kD proteins was elicited in guinea pigs that
      had been immunized with H37Rv sonicate. CONCLUSION: The 12 kD protein could be
      easily purified and could serve as a valuable serodiagnostic tool in the
      screening of TB cases from a large population in an endemic area.

PMID- 8136492
TI  - Superoxide dismutase activity of Mycobacterium tuberculosis isolated from
      tuberculosis patients and the immunoreactivity of superoxide dismutase from M.
      tuberculosis H37Rv.
AB  - OBJECTIVE: To determine the superoxide dismutase (SOD) activity from clinical
      isolates of Mycobacterium tuberculosis and to study the seroreactivity of SOD
      from M. tuberculosis H37Rv. DESIGN: Crude cell extracts of 16 strains of M.
      tuberculosis isolated from tuberculosis (TB) patients were assayed for SOD
      activity. SOD from H37Rv was partially purified and characterized, and the
      seroreactivity was studied by ELISA using sera from 36 active pulmonary TB and 31
      leprosy patients. RESULTS: SOD activity was detected in all the 16 strains of M.
      tuberculosis and also in the medium of logarithmic and stationary cultures of
      H37Rv. SOD activity from H37Rv extract was not affected by 1 mM KCN or by 5 mM
      H2O2 and was only 20% inhibited by 10 mM NaN3, suggesting that it is a Mn
      containing enzyme. SOD was partially purified from H37Rv extract by gel
      filtration chromatography as a tetramer of molecular weight (MW) of 80,000 and a
      subunit MW of approximately 23,000. A delayed type hypersensitivity was elicited
      by SOD in guinea pigs sensitized with H37Rv or M. leprae sonicate. ELISA using
      SOD as antigen indicated 100% positivity with TB sera, while 84% positivity was
      observed with leprosy sera. Western blotting with pooled TB and leprosy sera
      indicated the presence of antibodies to the 23 kD SOD protein. CONCLUSION: Our
      data indicate that M. tuberculosis strains are rich in SOD, and the secretion of
      SOD may play a valuable role in the pathogenesis of M. tuberculosis.

PMID- 8136493
TI  - Adrenocortical function and involvement in high risk cases of pulmonary
      tuberculosis.
AB  - SETTING: A regional hospital in Hong Kong. OBJECTIVE: To evaluate adrenocortical
      function in older patients admitted to hospital with active pulmonary
      tuberculosis (TB) and to determine whether adrenal insufficiency contributes to
      mortality in this high risk group. DESIGN: Adrenocortical function was assessed
      in 39 consecutive patients aged over 50 admitted to hospital with active
      pulmonary TB. Short Synacthen stimulation tests were performed before treatment
      and repeated at 2 months. In patients who died during treatment, a post-mortem
      examination was performed. Particular attention was paid to TB involvement of the
      adrenal glands. RESULTS: None of the patients had a subnormal basal cortisol
      concentration before treatment. 7 (18%) had raised basal cortisol concentrations
      and 16 (41%) had suboptimal cortisol responses to Synacthen stimulation. 14
      patients (36%) died during treatment. The basal cortisol concentrations were
      significantly higher in the non-survivors compared to the survivors (743.7 +/-
      288.5 vs 460.5 +/- 123.2 nmol/L, P < 0.0001). Autopsies were performed in 9
      patients who died during treatment. Tuberculous involvement of the adrenal glands
      was found in only 1 patient who had a high basal cortisol concentration. After 2
      months of treatment, all patients had normal cortisol concentrations and only 4
      had borderline suboptimal Synacthen responses. The basal cortisol concentrations
      were significantly higher at presentation compared to those at 2 months after
      treatment (570.4 +/- 243.8 vs 386.3 +/- 108.3 nmol/L, P = 0.0014). CONCLUSION:
      Adrenal insufficiency is uncommon in patients with pulmonary TB. Suboptimal
      cortisol responses to Synacthen usually reflect a hyperstimulated basal state
      secondary to stress. Treatment with anti-TB drugs causes reduction in basal
      cortisol with associated improvement in the Synacthen response.

PMID- 8136494
TI  - Tuberculosis of peripheral joints: a dilemma in diagnosis.
AB  - 15 cases of peripheral joint tuberculosis presenting to a tertiary referral
      hospital are reviewed. The presentation is characterized by an insidious onset
      with a slowly progressive, painful, ankylosed or swollen monarthropathy with a
      mean length of history of 6.5 +/- 7 years. The knee joint was involved in 7
      patients, hip in 6, elbow and shoulder 1 each. Significant systemic toxicity was
      absent, the white count was normal (mean 7.3 +/- 2.4 x 10(9)/1) and the
      erythrocyte sedimentation rate (ESR) was only slightly elevated (mean 31 +/- 23
      mm/first h). Features of extra-articular pulmonary tuberculosis were present in 7
      patients and periarticular findings were present (abscesses in 7 and sinuses in 4
      patients). Despite a characteristic presentation, the diagnosis was initially
      missed in 10, leading to delay in instituting correct treatment. One patient
      presented with osteoarthritis and a Baker's cyst. Definitive joint arthropathy
      was present in all patients. The highest diagnostic yield was with a combination
      of synovial histology, synovial fluid culture and direct smear examination for
      acid fast bacilli (14 patients) and lowest if direct smear examination was used
      alone (2 patients). Chemotherapy with rifampicin and isoniazid alone (3 patients)
      or with at least 1 other drug was given for a mean of 15 +/- 5 months. Apart from
      debridement/drainage surgery, fusion/excision arthroplasty was performed in 6
      cases and one had a total knee replacement. A heightened diagnostic acumen is
      needed in such cases.

PMID- 8136495
TI  - Serodiagnosis of tuberculosis: assessment of kaolin agglutination test.
AB  - Kaolin agglutination test (KAT), for the detection of anti-tuberculophospholipid
      antibodies for the serodiagnosis of tuberculosis, was performed on the sera of
      137 pulmonary and 276 extra pulmonary tuberculosis patients and 140 controls. The
      sensitivity and specificity of KAT was 86.9% and 100%, respectively, at the titre
      of 1:128 and more.

PMID- 8136496
TI  - Lung abscess due to coexisting Mycobacterium tuberculosis and anaerobic bacteria
      in a cavitary bronchogenic carcinoma.

PMID- 8136497
TI  - Non-reactive tuberculosis in an infant.

PMID- 8136498
TI  - External quality control of direct sputum smears from Sierra Leone, West Africa.

PMID- 8136499
TI  - Multidrug-resistant strains of tubercle bacilli isolated from pulmonary
      tuberculosis retreatment patients in Sierra Leone, West Africa.

PMID- 8136500
TI  - Persistent lung infection due to Mycobacterium szulgai.

PMID- 8136501
TI  - Corticosteroids as a risk factor for tuberculosis.

PMID- 8136502
TI  - Specificity of primers based on IS6110 to Mycobacterium tuberculosis complex DNA.

PMID- 8136503
TI  - Tuberculosis therapy and alphabet soup.

PMID- 8136504
TI  - Pain and the placebo in rehabilitation using TENS and laser.
AB  - The placebo effect of many health-related treatment is generally acknowledged.
      This paper discusses the role of the placebo in relation to pain perception and
      pain control. The theoretical basis of the placebo response is examined, followed
      by a discussion of the factors influencing the placebo response. Finally, the
      magnitude of the placebo response is explored specifically in relation to outcome
      measures and the efficacy of transcutaneous electrical nerve stimulation (TENS)
      and laser for pain relief.

PMID- 8136505
TI  - Mechanical back pain and the facet joint syndrome.
AB  - Mechanical back pain is a common disability often associated with the facet joint
      syndrome. Treatment is based on early, adequate pain relief with simple
      techniques of regional analgesia. In a few cases this is not enough and more
      sophisticated methods, such as radiofrequency denervation, cryo-analgesia and
      possibly intrathecal midazolam, are necessary. However, the main thrust of our
      approach is to treat the underlying structural disorder with strengthening of the
      back muscles and correction of postural abnormalities responsible for the
      mechanical back pain. Our report is based on an analysis of 83 patients who
      failed to respond to long periods of rest, suitable analgesic and allied drugs
      and other non-invasive measures. There had been no overriding indication for
      major surgery. A large number of these patients have been improved by our
      methods, but further work is in progress to extend the proportion of satisfactory
      results.

PMID- 8136506
TI  - Prediction of pain rehabilitation outcomes by motivation measures.
AB  - This study attempted to predict reduction in pain description, pain behaviour,
      and depression by measures of motivation and previous vocational development.
      Twenty-one patients randomly selected from an inpatient pain programme were given
      pre-admission the Goldberg Scale, a 2-h clinical interview synthesizing
      educational and vocational history, work values, interests, motivation to work,
      realistic assessment of pain disability and optimistic compared to pessimistic
      outlook towards the future. Repeated measures consisted of the McGill-Melzack
      Pain Questionnaire, the Pain Disability Index, and the Beck Depression Inventory,
      given at admission, discharge and follow-up. Pain was classified by the IASP
      categories. The Goldberg Scale predicted at p less than 0.05 level for reduction
      of subjective pain description on MMPQ and reduction of depressive symptoms on
      Beck, but failed to predict for reduction of pain behaviour at 0.05 level. A
      measure of motivation may be a useful adjunct to the broad array of measures to
      predict outcome in pain management programmes.

PMID- 8136507
TI  - The effects of a cognitive-behavioral pain management programme on the quality of
      work and employment status of severely impaired chronic pain patients.
AB  - This study examined changes in employment status and quality of work in 109
      chronic pain patients who underwent a cognitive-behavioural pain management
      course; 68% of patients were female, mean age was 45 years, mean pain chronicity
      10.7 years, 70% had spinal pain, and mean impairment on the Sickness Impact
      Profile was 26%. Twenty-six per cent of patients were employed at pre-treatment;
      the remaining 74% had been unemployed for 4.3 years on average. Measures of work
      status and quality, mood, pain, self-efficacy and walking performance were taken
      before admission, and at 1-, 6-, and 12-month follow-ups. Among employed patients
      quality of work scores improved by 35% from pre- to post-treatment (p < 0.01).
      Thirty per cent of previously unemployed patients returned to work during the 1
      year follow-up, although employment status fluctuated greatly during this period.
      Non-workers were generally more impaired than workers on most measures, but the
      same measures did not differentiate between those who successfully returned to
      work and those who remained unemployed.

PMID- 8136508
TI  - Mood assessment in chronic pain patients.
AB  - This pilot study was designed to identify the mood state of patients attending
      two pain clinics in the South of England and to identify the factors which are
      predictive of mood in patients with chronic pain. Patients were asked to complete
      a questionnaire which included a short bipolar mood profile, together with verbal
      rating scales to assess pain and contributory coping variables. The most commonly
      occurring negative moods were tension, worry and irritability. Lack of
      information was the best predictor of negative mood. Other variables which were
      found to be associated with negative mood included lack of sleep, occupation and
      emotional support, and financial problems.

PMID- 8136509
TI  - The socioeconomic impact of chronic pain.
AB  - A concern with the socioeconomic effects of chronic nonmalignant pain, as well as
      the human aspects, inspired a search of the literature for evidence in this area.
      The review has identified three main areas of interest, socioeconomic statistics;
      pain prevalence in the community, and the quality of life issues. A selection of
      the literature is reviewed here under these headings, and the conclusion
      indicates possible areas for further work.

PMID- 8136510
TI  - Pain in children: developing a programme of research.
AB  - Developing a programme of research is important in advancing the science and
      practice of a discipline. This paper addresses in general the steps taken in
      developing a programme of research on pain in children. It reports the results of
      studies undertaken to develop and test a Pain Assessment Tool for Children and
      gives an overview of a trajectory of studies currently in progress or under
      completion. Future plans to further develop this area of research are also
      presented and discussed.

PMID- 8136511
TI  - Ondansetron in the control of chemotherapy-induced and radiotherapy-induced
      emesis in children with malignancies.
AB  - The management of chemotherapy-induced nausea and emesis presents a major problem
      in children with cancer. The anti-emetic properties of the 5-HT3 receptor
      antagonist ondansetron are well documented in adults receiving cytotoxic
      chemotherapy. Experience in the treatment of children is still limited. Here we
      present a review of the literature on the anti-emetic treatment with ondansetron
      in children. Moreover, we provide recommendations on the use of ondansetron
      during anti-neoplastic chemotherapy and radiotherapy in pediatric oncology.

PMID- 8136512
TI  - Ondansetron in the treatment of nausea and vomiting induced by chemotherapy.
      Portuguese Ondansetron Study Group.
AB  - One-hundred and forty-five chemotherapy patients receiving cisplatin- and non
      cisplatin-containing regimens participated in an open evaluation of ondansetron,
      a 5-HT3 receptor antagonist, in the prophylaxis of acute and delayed nausea and
      vomiting. The study had two groups of patients, one receiving cisplatin
      containing regimens (Group A) and the other, non-cisplatin-containing regimens
      (Group B). There were 51 patients recruited to Group A. Ondansetron was given to
      these patients at a dose of 8 mg intravenously 15 min before chemotherapy,
      followed by an intravenous infusion for 24 h (1 mg/h), or 8 mg intravenously 4
      and 8 h after the start of cisplatin, followed by 8 mg orally three times/day for
      5 days. Ninety-four patients were recruited to Group B: these patients received
      ondansetron at a dose of 8 mg intravenously immediately before chemotherapy or 8
      mg orally 1-2 h prior to it, and 8 mg orally three times/day for 3-5 days. For
      acute emesis (first 24 h), complete control was achieved in 79.5% of Group A
      patients and in 78.1% of Group B. For delayed emesis (days 2-5), 79.7% of Group A
      patients and 84.6% of Group B were completely protected during the entire study
      period. Nausea was also well controlled with ondansetron; 83.2% (Group A) and
      86.5% (Group B) reported only mild nausea or no nausea at all. Ondansetron was
      effective in the control of both cisplatin- and non-cisplatin-induced emesis and
      well tolerated without any serious drug-related adverse events.

PMID- 8136513
TI  - Ondansetron in the treatment of nausea and vomiting. Introduction.

PMID- 8136514
TI  - Clinical studies to assess the economic impact of new therapies: pragmatic
      approaches to measuring costs.
AB  - Pragmatic clinical trials using unselected patients in normal clinical situations
      are more appropriate for the economic assessment of new drugs. However, standard
      clinical studies that do not reflect current practice are useful and at present
      the only source of information. Anti-emetic drug studies using granisetron and
      ondansetron have demonstrated that the overall economic impact of these drugs is
      equivalent to standard therapies such as metoclopramide. Thus, an efficient anti
      emetic drug with less frequent dosing, using a simplified dosage regimen and
      producing a reduction in anticipatory nausea and vomiting and in nursing time,
      may result in an overall reduction in cost. Decisions made purely on the basis of
      drug costs may be misleading and promote inefficient use of health resources.

PMID- 8136515
TI  - Modeling budgetary impact for decision makers.
AB  - The budgetary implications of using 5-HT3 receptor antagonists in the management
      of patients with chemotherapy-induced emesis is discussed. It was shown that
      treatment with 5-HT3 receptor antagonists in the acute phase of emesis resulted
      in relatively little additional cost when introduced into a normal management
      pattern of emesis control, and therefore seems justifiable. However, in delayed
      emesis there is a much more substantial budgetary impact with no proven clinical
      benefit, and therefore treatment does not appear to be appropriate in this
      situation.

PMID- 8136516
TI  - A framework for assessing therapeutic innovation.
AB  - Budgetary restraints have been used to limit the freedom of medical prescription.
      This paper proposes a simple approach to the evaluation of costs and benefits.
      First the efficacy of a new approach is defined and compared with the best care
      with existing means. The incremental gain is then compared with the true cost of
      both procedures. The innovation should be adopted only where the gain is high and
      the cost low (or at least only minimally increased). In cases of debatable gain
      and costs, detailed cost-benefit analysis and quality of life studies are needed.
      We conclude that at present, 5-HT3 receptor antagonists should only be used to
      control the acute phase of emesis.

PMID- 8136517
TI  - Assessing the benefits of anti-emetic innovation.
AB  - This paper reviews recent anti-emetic developments, with particular reference to
      the 5-HT3 receptor antagonists. These drugs are at least as effective as
      conventional regimens for controlling acute nausea and vomiting in patients
      receiving highly or moderately emetogenic chemotherapy and abdominal
      radiotherapy. They have less side effects than do alternative drugs. Improved
      control of acute nausea and vomiting by 5-HT3 receptor antagonists seems to
      reduce anticipatory symptoms in subsequent cycles. Dexamethasone enhances
      activity of 5-HT3 receptor antagonists in highly emetogenic chemotherapy.
      Improved control of acute nausea and vomiting by 5-HT3 receptor antagonists may
      remove one obstacle to offering palliative chemotherapy.

PMID- 8136518
TI  - The costs of health care: implications for anti-emetic therapy.
AB  - Health economists assess new drug innovations to improve choice. Decision-making
      techniques for cost analysis should include not only direct costs but costs in
      terms of increased health benefit, reduced mortality and improved quality of
      life. The use of anti-emetic drugs results in a significant improvement in the
      quality of life of patients and decision making on the use of anti-emetic drugs
      should fully evaluate this patient benefit.

PMID- 8136519
TI  - Properties and significance of a riboflavin-binding hexamerin in the hemolymph of
      Hyalophora cecropia.
AB  - A riboflavin-binding hexamerin isolated from pupal hemolymph of Hyalophora
      cecropia has a native M(r) of 510,000, subunit M(r) of 85,000, and a 5%
      carbohydrate content. An intrachain cross-link was confirmed in protease limit
      digests. Ellman titration confirmed the presence of a sulfhydryl group, which is
      needed for this linkage. Though Cu2+ is known to promote the linkage, heavy
      metals were not detected in the isolate. Heat denaturation released ligand with
      the absorbency, fluorescence spectra, and chromatographic behavior of riboflavin.
      Binding resulted in substantial quenching of the fluorescence of both the
      isoalloxazine in riboflavin and of aromatic groups in the apoprotein. Kinetic
      analysis indicated a KD of 2.5 x 10(-7) M for riboflavin, 1.3 x 10(-7) M for
      lumiflavin, and greater than 1 x 10(-6) M for FMN and FAD. Over four moles of
      flavin were bound per mole of hexamerin. The amount of riboflavin in pupal
      hemolymph is sufficient to occupy only 2-3 of these sites. Riboflavin is also
      associated with lipophorin and vitellogenin, but the molar ratios after protein
      isolation were low. On a standard laboratory diet, riboflavin is in great excess,
      but most of it is apparently excreted before the apoprotein first appears in the
      hemolymph, just before wandering. The concentration of riboflavin-binding
      hexamerin rises to 15-30 mg/ml in pupae; relative to other hexamerins, very
      little is stored in the fat body. All of the apoprotein and 75% of riboflavin
      disappear from the hemolymph during adult development. An amount of flavin at
      least equal to that stored in pupal hemolymph is transferred to the eggs formed
      during this period.

PMID- 8136520
TI  - Actions of acromelic acid on nervous system L-glutamate receptors.
AB  - Acromelic acid, a naturally occurring kainoid, isolated from the mushroom
      Clitocybe acromelalga, is a weak displacer of [3H]L-glutamate binding to
      cockroach (Periplaneta americana) nerve cord membranes. Acromelic acid (1 mM)
      displaces approximately 60% of specifically bound [3H]L-glutamate. When applied
      by bath perfusion to the cell body membrane of the cockroach fast coxal depressor
      motor neurone, acromelic acid generated slow, prolonged, dose-dependent
      depolarizations at concentrations of 0.3 microM and above. Thus acromelic acid is
      among the most potent of the excitatory amino acids tested to date on insect
      neurones.

PMID- 8136521
TI  - Distribution of FGF-2 suggests it has a role in chick limb bud growth.
AB  - We developed and characterized antibodies specific for FGF-2 and used them to
      locate FGF-2 during chick embryo development. A series of micrographs
      demonstrated the progression of FGF-2 staining during development of the
      different tissues and organs. FGF-2 was present in the ectoderm covering the
      entire embryo, muscle cells, nervous system, neural crest cells, and mesonephros.
      FGF-2 was also present in the limb from initiation of budding through
      differentiation. The limb ectoderm and subjacent mesoderm showed the strongest
      immunostaining, with lower levels in the center of the bud. However, the
      distribution of FGF-2 positive cells in the mesoderm was not homogeneous. This
      heterogeneity was not due to cell cycle specific distribution of FGF-2 protein,
      as flow cytometric analysis showed that FGF-2-positive cells were distributed
      throughout the cell cycle. However, the amount of anti-FGF-2 fluorescence varied
      most during G1, consistent with the possibility that FGF-2 is low after M phase
      and increases during G1. A bioassay was used to demonstrate FGF-2 levels in the
      wing ectoderm were approximately 2.7-fold greater than in the mesoderm. We
      propose that the location of FGF-2 in the embryo is consistent with a role in
      epithelial-mesenchymal interactions; in the limb bud it may prevent
      differentiation and permit limb outgrowth and subsequent expression of patterning
      events.

PMID- 8136522
TI  - Spatiotemporal expression of pregnancy-specific glycoprotein gene rnCGM1 in rat
      placenta.
AB  - As a basis towards a better understanding of the role of the pregnancy-specific
      glycoprotein (PSG) family in the maintenance of pregnancy, detailed
      investigations are described on the expression of a recently identified rat PSG
      gene (rnCGM1) at the mRNA and protein levels. Using specific oligonucleotide
      primers, rnCGM1 transcripts were identified after reverse transcription,
      polymerase chain reaction, and hybridization with a radiolabelled, internal
      oligonucleotide. Transcripts were only found in significant amounts in placenta.
      In situ hybridization visualized rnCGM1 transcripts at day 14 post coitum (p.c.),
      in secondary trophoblast giant cells and in the spongiotrophoblast. Only those
      secondary giant cells lining the maternal decidua were positive. In contrast,
      primary giant cells did not contain rnCGM1 mRNA. At day 18 p.c., rnCGM1
      transcripts were almost exclusively detectable in the spongiotrophoblast. No
      rnCGM1 transcripts were found in rat embryos of these two developmental stages.
      Rabbit antisera were generated against the amino-terminal immunoglobulin variable
      like domain and against a synthetic peptide containing the last 13 carboxy
      terminal amino acids of rnCGM1. Both antisera recognized a 124 kDa protein in day
      18 rat placental extracts as identified by Western blot analysis. The anti
      peptide antiserum recognized a 116 kDa protein in the serum of a 14 day p.c.
      pregnant rat that is absent from the sera of non-pregnant females. Taken
      together, these results confirm exclusive expression of rnCGM1 in the rat
      trophoblast, but unlike human PSG, negligible or no expression is found in other
      organs, such as fetal liver or salivary glands, indicating a more specialized
      function of rnCGM1. Its spatiotemporal expression pattern is conducive with a
      potential role of PSG in protecting the fetus against the maternal immune system
      and/or in regulating the invasive growth of trophoblast cells.

PMID- 8136523
TI  - Proliferation and migration of primordial germ cells in We/We mouse embryos.
AB  - We have examined the numbers and distribution of primordial germ cells in We/We,
      We/+, and +/+ mouse embryos using Southern blotting to determine embryo
      genotypes. At early somite stages (5-7 somites: approximately 8 1/2 days post
      coitum [dpc]) there are 50 to 100 germ cells in embryos of all genotypes. The
      number of germ cells in We/+ and +/+ embryos then begins to increase: at later
      somite stages (17-19 somites: approximately 9 1/2 dpc) they number about 200, and
      by 10 1/2 dpc there are approximately 725 We/+ and 850 +/+ germ cells. During
      this time, however, the number of germ cells in We/We embryos remains less than
      100. At 8 1/2 dpc, the distribution of germ cells in the hindgut endoderm is the
      same in all genotypes. By 9 1/2 dpc, 30% of We/We germ cells are found in ectopic
      sites (allantois and vitelline artery); germ cell distribution along the length
      of the hindgut appears normal, but germ cells remain confined to the floor of the
      gut in We/We embryos, rather than being distributed around its circumference as
      in the other two genotypes. By 10 1/2 days, the migration of We/We germ cells
      through the dorsal mesentery lags behind that of the other genotypes, and a
      larger proportion remains in the gut wall.

PMID- 8136524
TI  - Modulation of contractile protein gene expression in fetal murine crural muscles:
      emergence of muscle diversity.
AB  - The modulation of contractile protein gene expression in mouse crural muscles
      (i.e., muscles located in the region between the knee and ankle) during the fetal
      period (defined as 15 days gestation to birth), resulting in diversity among and
      within these muscles, has been evaluated with in situ hybridization and
      correlated with morphogenetic events in the extensor digitorum longus and soleus
      muscles. During the fetal period extensive secondary myotube formation occurs in
      the crural muscles, and the myotubes become innervated (Ontell and Kozeka
      [1984a,b] Am. J. Anat. 171:133-148, 149-161; Ontell et al. [1988a,b] Am. J. Anat.
      181:267-278, 181:278-288). At 15 days gestation, hybridization with 35S-labeled
      antisense cRNA probes demonstrates the accumulation of transcripts for alpha
      cardiac and alpha-skeletal actin; MLC 1A, MLC 1F, and MLC 3F; and MHC emb, MHC
      pn, and MHC beta/slow. At 16 days gestation, accumulation of MHC emb transcripts
      is reduced (as compared with earlier developmental stages); intensity of signal
      following hybridization with the probe for alpha-skeletal actin is, for the first
      time, equal to that for the cardiac isoform; and MLC 1V mRNA accumulation is
      discernible. At this stage, variation in transcript accumulation for some mRNAs
      among and within crural muscles becomes evident. Two factors may play a role in
      the selective distribution of these transcripts: 1) the stage of muscle
      maturation; and 2) the future myofiber type. At 16 days gestation anterior crural
      muscles (which mature approximately 2 days before posterior crural muscles;
      Ontell and Kozeka [1984a,b], ibid., Ontell et al. [1988a,b], ibid.) exhibit a
      greater accumulation of transcripts for alpha-skeletal actin and for MLC 3F than
      is found in posterior crural muscles. In muscles that in the neonate are
      composed, in large part, of slow myofibers, MHC beta/slow and MLC 1V mRNAs
      accumulate in greater amounts, whereas MHC pn transcripts are less abundant in
      the soleus muscle than in other crural muscles. By 19 days gestation
      regionalization of transcript accumulation is more pronounced. The soleus muscle,
      a predominantly slow twitch muscle in the newborn mouse (Wirtz et al. [1983] J.
      Anat. 137:109-126) exhibits strong signal after hybridization with probes
      specific for MHC beta/slow and MLC 1V. While the level of transcript accumulation
      for the development isoforms, MHC emb, MLC 1A, and alpha-cardiac actin, is
      greatly reduced in most crural muscles at 19 days gestation, these transcripts
      persist in the soleus muscle at levels equal ot or exceeding their amount in limb
      muscles of 13 day gestation mouse embryos.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8136525
TI  - Differential expression of muscle regulatory factor genes in normal and
      denervated adult rat hindlimb muscles.
AB  - Skeletal muscle represents an excellent model system in which to examine
      regulatory mechanisms that modulate gene expression in the mature adult organism.
      Individual muscle fibers can be categorized as fast- or slow-twitch based upon
      several physiological and molecular criteria, including metabolic enzyme activity
      and contractile protein isoforms. Each property can be influenced by a variety of
      factors such as changes in motor neuron activity or alterations in hormone
      levels, although the molecular pathways by which environmental factors affect
      gene expression remain largely unknown. As a first step in identifying potential
      regulators of fiber-type diversity, the expression patterns of four basic/helix
      loop-helix muscle regulatory factors (MRFs), referred to as MyoD, myogenin, Myf
      5, and MRF4, were examined in normal adult rat muscles which differed in their
      phenotypic properties. As expected, all four MRFs were expressed at detectable
      levels in the muscles studied. However, different muscles accumulated different
      proportions and combinations of MRF transcripts. For example, myogenin expression
      was maximally detected in slow-twitch muscles whereas MyoD transcripts were found
      predominantly in muscles exhibiting a fast-twitch phenotype. Induced phenotypic
      changes in two fast-twitch muscles via denervation lead to a large and rapid
      increase in transcript levels of all four MRFs as early as 24 hr following
      denervation, with myogenin transcripts approaching 150-200-fold higher levels
      than innervated contralateral muscles within 7 days. These results suggest that
      myogenin, as well as the other three MRFs, may be involved in both the initial
      establishment as well as maintenance of fiber-type diversity in the developing
      organism.

PMID- 8136526
TI  - Expression of tumor necrosis factor-alpha (TNF alpha)-cross-reactive proteins
      during early chick embryo development.
AB  - We have investigated the expression of tumor necrosis factor-alpha (TNF alpha)
      cross-reactive proteins during the early development of the chick embryo from day
      1 to day 6 (H-H stages 5-29) using a polyclonal antibody and two monoclonal
      antibodies to recombinant mouse TNF alpha. We have confirmed the cross-reactivity
      of the antibodies with chicken tissue in Western blotting studies. Proteins of 50
      kDa and 70 kDa, showing anti-TNF alpha cross-reactivity, have been identified
      during early chick development. In addition, both monoclonal antibodies recognize
      a 120 kDa protein. These molecules probably represent cytosolic or transmembrane
      TNF-alpha-like proteins, similar to those previously identified on the surface of
      cytotoxic T-lymphocytes. We show by ultrastructural cytochemistry that
      immunoreactivity can be detected at the surfaces of some cells, suggesting that
      at least some of the antigen is membrane-associated. The proteins are shown to
      have a widespread tissue distribution during this period of development.
      Immunoreactivity is first detected in the gastrulating embryo, in the mesoderm
      and the endoderm. By day 2, expression is confined to the ectoderm and the
      endoderm, while at day 3 expression appears in the myotome, the notochord, and in
      nervous tissue. At day 4 the distribution of reactivity is more extensive and
      includes the notochord, the sclerotome, and the myotome, while the cranial and
      spinal nerves also become intensely immunoreactive. Also at this stage, neural
      tube reactivity becomes localized to the marginal neuroepithelial zone, and the
      lens fibers become positive. This distribution of staining then persists until 6
      days of development. We hypothesize that the expression of TNF alpha-cross
      reactive proteins in early development could be indicative of a role for them in
      programmed cell death (apoptosis) during differentiation of the notochord, the
      lens, and the nervous system, and in tissue remodeling.

PMID- 8136527
TI  - [Scanning electron microscopy and microcrystals in articular diseases].
AB  - The value of scanning electron microscopy (SEM) in the study of crystals in
      articular diseases is underlined in several cases of examination of joint fluid,
      or crystal deposits in articular or periarticular tissues obtained by
      percutaneous or surgical treatment with chemical and crystallographic
      correlations. Apatite crystals. Two deposits of hydroxyapatite of the rotator
      cuff were studied by SEM, crystallographic techniques and chemical analysis. SEM
      study showed spherical aggregates of various size. Urate crystals. Three tophi
      were observed by SEM, with crystallographic techniques and chemical analysis.
      Their needle-shape and their great size (20 m) were characteristic. Calcium
      pyrophosphate crystals. In a case of typical clinical and radiological features,
      examination of joint fluid, with chemical correlation showed shorter and thicker
      crystals than those or urate. The precise identification of crystals is based on
      sophisticated crystallographic techniques such as X-ray diffraction, although SEM
      allows an accurate and quite simple morphologic study, most often sufficient.

PMID- 8136528
TI  - [The physiologic cell death areas in mouse embryo branchial arches: a morphologic
      and histochemical study with teratologic implications].
AB  - The association of a morphological study using semi-thin sections with a
      histochemical approach of the programmed cell death phenomenon in mouse embryo
      branchial arches permits to observe a spatio-temporal dorsoventral gradient. It
      also confirms that physiological cell death occurs in a mesectodermal population.
      The study of the increase of this process induced by retinoic acid administration
      provides some hypothesis which may explain the teratogenicity of the retinoid
      family.

PMID- 8136529
TI  - [Macroscopic vascularization of the adult sternum. Implications of removal of the
      internal thoracic arteries].
AB  - The most of the arterial vascularisation of the adult sternum is on the
      dependence of the internal thoracic arteries. The best results of the aorto
      coronary by-pass starting from this arteries are however subjected to more
      infectious complications. The study of this arterial supply, in "surgical"
      conditions, after sternotomy and ablation of one or two internal thoracic
      arteries show this devascularization. The residual arterial supply is only
      constituted by thin branches coming from intercostal arteries.

PMID- 8136530
TI  - [Critical view of methods for studying the motion of the thoracic and lumbar
      spine in man].
AB  - The study on motion of human thoracic and lumbar spine is difficult. To examine
      this point, technology will be divided in six class and each of them being
      benefits and disadvantages. Owing to ethics, authors agree with skin tapes
      allowing to know imperfectly freeness of motion without risks.

PMID- 8136531
TI  - [The lymphatic drainage of the esophagus].
AB  - The study was carried on 65 cadavers: 50 adults and 15 newborns. The esophagus
      was injected at the level to the neck 16 times, in the thorax at the superior
      level 18 times, middle level 30 times and inferior level 21 times. The lymphatic
      pathways were named short when joining the nodes at the same level, half long
      when joining the nodes of the neighbouring level, long when joining third level,
      and very long. At the level of the neck were injected 24 lymph nodes chains: in
      12.5% of the cases the pathways were long, joining the nodes of the arch of the
      Azygos vein. At the superior thorax level were injected 27 chains: half of the
      pathways were half-long: 7.5% long (-joining the pharynx once and the cardia
      once). At the middle thorax level were injected 37 chains: 27% were long and very
      long. At the inferior thoracic level were injected 21 chains: The pathways were
      half long in half cases and very long in 15% of the cases joining the cervical
      nodes. These results compare with experience in oncology and justify the need for
      total esophagectomies and nodes resection of all levels in surgical treatment of
      carcinomas of the esophagus.

PMID- 8136532
TI  - Cellular and subcellular alterations of the thyroid gland in rats caused by
      lithium carbonate.
AB  - Biochemical, hematologic, histometric, structural and ultrastructural changes
      were studied in the thyroid gland of rats, whom were administered Lithium
      carbonate. It was noted that (1) the Li carbonate had a cumulative effect on the
      serum; (2) T3 and T4 hormones in the blood decreased throughout the experiment;
      (3) the red blood cells, hemoglobin, hematocrit, platelets and leukocytes
      decreased gradually; (4) the diameter of the thyroid follicles, the size of the
      follicular cells and colloid droplets decreased, whereas the stroma was invaded
      by a greater number of collagen fibers and blood capillaries.

PMID- 8136533
TI  - [Anatomic abnormalities of the genital tract in ano-rectal malformations].
AB  - Of 152 patients with imperforate anus, 16 girls -25%), 10 boys (15%) have an
      abnormality of the genital tract and real frequency seems underevaluated. In
      girls, vaginal septum, bicornuate and didelphys uterus are mostly diagnosed,
      associated with severe unilateral upper urinary tract malformations. Absent
      vagina and uterus (Rokitansky syndrome) must be seen at birth, to preserve
      perineal fistula used to fashion a vagina at the time of the abdomino-perineal
      fistula pull through. In boys hypospadias, ectopia and uretero-vas anastomosis
      are the most frequent malformations.

PMID- 8136534
TI  - [Man among the primates. His position after multivariate analysis of his
      mandible].
AB  - Multivariate analysis are applied to 31 ensembles (species of Primates or human
      breeds), in 31 mandibular linear parameters. A reciprocal averaging show that
      first factorial plane reproduce the Simpson classification, simplified in 4
      groups, with 63.3% of whole inertia. Discriminant analysis calculated with 13
      parameters, situates these 4 groups in 3 planes. The D2 Mahalanobis generalised
      distance is calculated between all groups. The most contributive parameters to
      generalised distances are inter-molar width and breadth between foramen mentales.

PMID- 8136535
TI  - Spectrum of dermatological lesions in renal allograft recipients in a tropical
      environment.
AB  - A total of 157 renal allograft recipients were followed for over 1-23 months for
      the development of dermatological lesions. The non-infective lesions related to
      immunosuppressive drugs included cushingoid features in 133 (84.7%), xerosis in
      120 (76.4%), striae in 69 (43.9%), hypertrichosis in 65 (21.6%), facial erythema
      in 42 (26.7%) and friable skin in 34 (21.4%) patients. Of the infective lesions,
      cutaneous mycoses were the most frequent (82.6%) and included tinea corporis and
      cruris in 82 (52.2%), tinea versicolor in 21 (13.3%), candidiasis in 7 (4%),
      onychomycosis in 4 (2%) and cryptococcosis in 2 (1.2%) patients. Viral infections
      included those due to herpes zoster in 17 (10.8%), herpes simplex in 5 (3.1%) and
      viral warts in 13 (8.2%) patients. Cutaneous malignancy was seen in 1 patient
      only.

PMID- 8136536
TI  - Effects of fluid volume changes during hemodialysis on the biophysical parameters
      of the skin.
AB  - Water plays an important role in maintaining skin suppleness and elasticity. We
      used hemodialysis as a model to investigate the effects on biophysical properties
      of the skin induced by removal of fluids and water from the body. The following
      parameters have been investigated before and immediately after a hemodialysis
      session: body weight, skin elasticity and distensibility, skin hydration,
      transepidermal water loss (TEWL) and skin thickness. A significant decrease was
      recorded after treatment in body weight, skin thickness (p < 0.01) and skin
      elasticity (p < 0.01). Significant linear correlations were found between stratum
      corneum water content, skin distensibility and TEWL. The data reveal that rapid
      removal of body fluids influences skin biophysical properties: early changes in
      skin thickness and ground substance occur in the dermis and affect mechanical
      properties of the skin. The decrease in water content in the upper layers of the
      skin occurs at a later stage and influences skin hydration rather than TEWL. This
      model is a useful tool to investigate water kinetics through the skin.

PMID- 8136537
TI  - Drug-induced solar urticaria due to repirinast.
AB  - We describe the first case of drug-induced solar urticaria due to repirinast, an
      antiallergic drug developed and introduced into the market in Japan in 1987. The
      patient was a 72-year-old woman who had been on repirinast for 1 year and 8
      months. She developed urticaria immediately after an irradiation with 1.5 J/cm2
      of UVA, and the provocation test confirmed that repirinast was responsible for
      the urticarial reaction. The action spectrum of the urticarial reaction was
      deduced to be 320-350 nm. Passive and reverse passive transfer test results were
      both negative. However, intradermal injection of patient serum, obtained while
      she was on repirinast and irradiated in vitro with UVA, demonstrated positive
      reactions both in the patient and in a normal volunteer. Our findings suggest
      that nonallergic mechanisms are involved in the reaction. However, the rarity of
      the phenomenon also suggests an association with some allergic mechanisms.

PMID- 8136538
TI  - Acitretin biotransformation into etretinate: role of ethanol on in vitro hepatic
      metabolism.
AB  - The aim of this study was to investigate the possible esterification of acitretin
      into etretinate by using hepatocytes in primary culture from the rat, monkey, dog
      and man. With rat and human hepatocytes, etretinate was detectable only when
      ethanol was co-administered with acitretin. With monkey and dog cells, traces of
      etretinate were found without ethanol addition, but the esterification of
      acitretin was highly enhanced by ethanol. The metabolic profile was not changed
      when cells were pre-incubated with ethanol. Therefore acitretin seems to act
      rather as a substrate than an enzymatic inducer.

PMID- 8136539
TI  - The risk of sensibilization and contact urticaria upon topical application of
      fumaric acid derivatives.
AB  - Systemic and sometimes topical therapy with fumaric acid (FA) and its derivatives
      is used in the treatment of psoriasis. Scattered data show that the topical
      application of these derivatives elicits side effects. Application of FA and some
      derivatives on the skin was accompanied by perilesional skin irritation, macular
      papular rashes and urticarial reactions. In order to determine the irritating and
      sensitizing properties of FA derivatives we used a cytotoxicity, flank
      irritation, ear swelling and guinea pig maximization test. The results of the
      cytotoxicity test demonstrated that dimethylfumarate (DMF) was the most toxic
      derivative. DMF induced also contact-urticarial reactions in contrast to mono
      ethylfumarate (MEF). Challenge experiments with FA, MEF and DMF in MEF- and DMF
      sensitized guinea pigs demonstrated that both MEF and DMF are moderate contact
      sensitizers. In DMF-sensitized animals cross-reactions with MEF were found. As
      DMF and MEF have cytotoxic, contact-urticarial and/or sensitizing properties,
      topical application should be avoided.

PMID- 8136540
TI  - Calcitriol (1 alpha,25-dihydroxyvitamin D3) ointment in psoriasis, a safety
      tolerance and efficacy multicentre study.
AB  - 30 patients were treated with daily application of calcitriol (1 alpha, 25
      dihydroxyvitamin D3) ointment 15 micrograms/g in white petrolatum. The patients
      were divided into three groups according to the size of their total area of
      psoriasis. They were treated for 6 weeks, and investigated first with weekly and
      then with two-weekly estimations of calcium metabolism (serum calcium, 24-hour
      urinary calcium, parathyroid hormone, 25-hydroxyvitamin D3 and calcitriol).
      Ninety percent of the patients cleared or improved and there were no significant
      side effects or local intolerance. Cosmetic acceptance was good. No clinically
      significant changes in calcium metabolism were observed in spite of calcitriol
      application ranging between 73.98 and 306.10 micrograms daily (normal daily
      synthesis being 1-2 micrograms).

PMID- 8136542
TI  - Lipodystrophia centrifugalis abdominalis infantilis occurring in the neck.
AB  - We report a Japanese girl with atypical lipodystrophia centrifugalis abdominalis
      infantilis. The initial lesion developed on the neck as an area of erythema which
      showed centrifugal spread to the nape, submandibular area and upper breast and
      central fading to leave a residual depression and purplish brown pigmentation
      symmetrically. A central depression on the neck, nape, submandibular area and
      upper breast was surrounded by a distinctive erythematous, slightly elevated and
      indurated border. Histological examination of the erythematous border revealed
      inflammatory changes in the subcutaneous fat. Although this patient was affected
      in an unusual site, we concluded that she had lipodystrophia centrifugalis
      abdominalis infantilis, because of the overall features of the lesions.

PMID- 8136541
TI  - Evaluation of different treatment methods in patients with psoriasis and content
      of kallikrein and kallikreinogen in blood plasma.
AB  - 158 patients with different forms of psoriasis were examined for the content of
      kallikrein and kallikreinogen in blood plasma and treated by different
      preparations including andecalin and dilminal-D. Changes in the kallikrein-kinin
      system may play a role in the development of psoriasis. The aim of this study was
      to investigate the relationship of changes in the kallikrein-kinin system induced
      by andecalin and dilminal-D and the clinical course of psoriasis. Determination
      of kallikrein and kallikreinogen content in blood plasma was made according to
      the methods of Paskhina and Krynskaya. Almost all psoriatic patients showed high
      kallikrein and kallikreinogen levels in blood plasma. We conclude that changes in
      the kallikrein-kinin system are involved in the pathogenesis of psoriasis.
      Andecalin and dilminal-D preparations resulted in a marked amelioration of
      psoriasis.

PMID- 8136543
TI  - Mutilating syringoacanthoma.
AB  - Syringoacanthoma is a rare tumor derived from the eccrine acrosyringium; very few
      cases have been reported. The nosology of this tumor remains controversial. We
      present a new case of syringocanthoma occurring in a 43-year-old woman; the
      lesion lasted for more than 30 years and caused partial destruction of the
      earlobe. Histopathologic examination showed a hyperkeratotic intraepidermal
      tumor, with many large cavities lined by an eosinophilic cuticle and filled with
      a PAS-positive substance. This case is probably a mutilating variant of
      syringoacanthoma, despite benign histopathologic features.

PMID- 8136544
TI  - Confluent and reticulated papillomatosis: a case with concurrent acanthosis
      nigricans associated with obesity and insulin resistance.
AB  - A 19-year-old Japanese man with confluent and reticulated papillomatosis (CRP) is
      presented. He was an obese and dark-complexioned man, who had impaired glucose
      tolerance and hyperinsulinemia. The clinical and histological findings were
      consistent with the diagnosis of CRP. He also had acanthosis nigricans (AN) on
      his axillae and nape. Neither spores nor hyphae were detected from scales;
      antifungal treatment had no benefit. Although the reduction of his weight was
      unsuccessful, oral etretinate therapy resulted in considerable improvement of
      both CRP and AN. We reviewed previous case reports in terms of the relation
      between CRP and AN. Although the two conditions are usually differentiated
      because of their distinctive clinical features, a close relationship was noted
      between CRP and AN.

PMID- 8136545
TI  - Biclonal Sezary syndrome with capillary leak syndrome.
AB  - Sezary syndrome is a rare, usually monoclonal proliferation of T lymphoid cells.
      We report a case of this form of cutaneous T cell lymphoma with highly probable
      biclonality of neoplastic proliferation. Biclonality in malignant lymphoma is a
      rare feature, until now generally reported in B cell lymphoma. Its identification
      by accurate immunological studies could be of importance since one of the two
      populations can exhibit a less differentiated phenotype requiring a more
      aggressive therapeutic regimen than usual. The occurrence of anasarca in our
      patient was probably due to capillary leak syndrome, already discussed in another
      case of peripheral T cell lymphoma.

PMID- 8136546
TI  - Brown papules and leukoderma in Darier's disease: clinical and histological
      features.
AB  - We report a Japanese case of Darier's disease with brown and white papules or
      maculae distributed on the neck, trunk and dorsa of hands. Both brown papules and
      leukoderma showed typical histological features of Darier's disease. Moreover,
      there were much fewer melanocytes and melanosomes in the epidermis of both
      lesions. The corneal layer of the brown papules was far thicker than that of the
      leukoderma. Therefore, the thick corneal layer of the brown papules may prolong
      the retention of a few melanosomes or a little melanin to induce
      hyperpigmentation, while the thin corneal layer of leukoderma may not do so,
      thereby producing hypopigmentation. The difference in clinical and histological
      courses after involvement of melanocytes was proposed to be the cause of the
      discrepancy between the previous reports. We conclude that leukoderma was the
      primary lesion, the postinflammatory depigmented spots, or the atypical or
      subclinical eruption of Darier's disease.

PMID- 8136547
TI  - Autoerythrocyte sensitization syndrome with thrombocytosis.
AB  - A case of autoerythrocyte sensitization syndrome in a 59-year-old female is
      reported. She had several episodes of circular ecchymoses on her left thigh.
      Intradermal injection of autoerythrocytes reproduced a similar ecchymosis.
      Thrombocytosis was detected and treated with busulfan which induced a delayed
      improvement of the ecchymosis outbreaks over 2 years of follow-up.

PMID- 8136548
TI  - Melorheostosis with associated minimal change nephrotic syndrome, mesenteric
      fibromatosis and capillary haemangiomas.
AB  - Melorheostosis is a benign, rare, congenital disorder of hyperostosis of one or
      more bones. Associated soft tissue abnormalities are often observed. A case of
      melorheostosis with minimal change nephrotic syndrome, mesenteric fibromatosis
      and capillary haemangiomas is reported. A congenital mesenchymal defect occurring
      early in embryonic life is suggested.

PMID- 8136549
TI  - Primary infection by human parvovirus B19.

PMID- 8136550
TI  - Treatment of melasma with potent topical corticosteroids.

PMID- 8136551
TI  - Mucosal fixed drug eruption.

PMID- 8136552
TI  - Hair discoloration caused by etretinate.

PMID- 8136553
TI  - Papular-purpuric 'gloves and socks' syndrome: not only parvovirus B19.
AB  - We previously described an acute dermatosis characterized by pruritic
      erythematous and slightly papular lesions on the hands and feet in a 'gloves and
      socks' distribution associated with oral aphthoid lesions and fever (papular
      purpuric 'gloves and socks' syndrome = PPGSS). We strongly suspected a viral
      origin, but serologic tests for a large panel of viruses remained negative.
      Subsequently, 2 cases of PPGSS with serologic evidence of a parvovirus B19
      infection have been reported in the literature. Since then we observed 5
      additional patients with a PPGSS. Parvovirus B19 infection could be confirmed in
      only 2 cases. Our findings suggest that the PPGSS can be another, yet undescribed
      manifestation of parvovirus infection. However, this cannot be shown in all the
      cases. As the papular acrodermatitis of childhood, this syndrome may be caused by
      various viral agents.

PMID- 8136554
TI  - Multiple non-melanoma skin cancer: evidence that different MHC genes are
      associated with different cancers.
AB  - HLA DR frequencies of patients with multiple non-melanoma skin cancers were
      analysed. There were significant differences in the frequencies of HLA DR1, DR4
      and DR7 between patients who only had basal cell carcinomas and patients who had
      both basal and squamous cell carcinomas. There were significant differences in
      the frequency of HLA DR53 between the two groups. This antigen is in linkage
      disequilibrium with HLA DR4 and DR7, and it is not possible to distinguish the
      primary susceptibility locus.

PMID- 8136555
TI  - Chronic venous stasis: not a predisposing factor for basal cell carcinoma on the
      leg. A histopathological study.
AB  - A histopathological study of 125 cases of basal cell carcinoma (BCC; out of 5,475
      over a period of 5 years) occurring on the leg was performed. Nodular and
      superficial BCC were the most common patterns. No sclerosing type was observed,
      although prominent fibrosis was present in some cases of BCC associated with
      severe stasis changes. Stasis changes were found only in 25% of the cases
      suggesting that they do not represent a predisposing factor for the development
      of BCC on the leg.

PMID- 8136556
TI  - DNA flow-cytometric analysis of basal cell carcinomas and its relevance to their
      morphological differentiation: a retrospective study.
AB  - DNA flow cytometry (FCM) was performed on archived material of 82 basal cell
      carcinomas (BCC), using Hedley's technique. Sixty-five samples were analysed.
      Biopsy samples were classified in five groups depending on their morphological
      differentiation: solid, cystic, adenoid, keratotic and metatypical. Two
      parameters were studied: proliferative index and DNA index. Statistical analysis
      revealed that BCC with keratinizing or metatypical differentiation had a greater
      amount of aneuploidy when compared with BCC without particular differentiation
      (solid and cystic) or aneuploid differentiation (p < 0.001). The proliferative
      indices were significantly different in the four groups. DNA FCM of BCC confirms
      the value of morphological classifications and gives another example of
      aneuploidy in a tumour with low aggressiveness.

PMID- 8136557
TI  - Relatively immediate relaxant effects of cholera toxin on isolated rabbit blood
      vessels.
AB  - A study was made on the relatively immediate relaxant effect of cholera toxin
      (CTX) on the isolated ear artery, thoracic aorta and saphenous vein of the
      rabbit. Both preparations of CTX, containing sodium azide (NaN3) and azide-free,
      showed no effect on the non-precontracted artery, but CTX containing NaN3 relaxed
      the moderately precontracted blood vessels with methoxamine promptly, i.e., with
      a time course of min order. However, the immediate relaxation produced by CTX
      containing NaN3 was attributed mainly to NaN3. Azide-free CTX, on the other hand,
      at 1-10 micrograms/ml gradually produced concentration-dependent relaxation of
      the precontracted vessels. The relaxant effects of CTX on the vessels were slow
      and long-lasting, i.e., with a time course of 10 min order. The relaxation
      induced by CTX was not influenced by the removal of endothelium nor by
      pretreatment with 10 microM indomethacin, 3 microM atropine or 3 microM
      propranolol. Activation of protein kinase C by a phorbol ester inhibited the
      relaxant effect of CTX. These results indicate that CTX relaxes the blood vessels
      by directly acting on the smooth muscles, without mediation by known endogenous
      relaxing factor, such as endothelium-derived relaxing factor (EDRF = NO) or
      prostaglandin I2 (prostacyclin) and by muscarinic receptor or beta-adrenoceptor.

PMID- 8136558
TI  - [Elevation of spontaneous tone and effects of antihypertensive treatments in
      arterial smooth muscle of spontaneously hypertensive rats].
AB  - Mechanisms of elevation of active tone in arterial smooth muscle of spontaneously
      hypertensive rats and effects of antihypertensive treatments are reviewed.
      Spontaneously hypertensive rats are created by Okamoto et al. and classified
      mainly into three strains, SHR, SHRSP and M-SHRSP. Blood pressure of the rats is
      higher in this order. The aortic smooth muscle of these rats exhibits elevation
      of the active tension (tone) under non-stimulated condition. The active tone is
      greater as the blood pressure of the rats elevated and good correlation between
      blood pressure and active tone can be obtained. The active tone is sensitive to
      extracellular Ca and abolished by the removal of extracellular Ca or by the
      application of Ca-antagonists. It is also associated with increased intracellular
      Ca level. These results indicate that the active tone is brought about by
      increase in voltage-dependent Ca channel opening of the cell membrane. Increased
      voltage-dependent Ca channel opening, i.e. membrane depolarization and increased
      inward Ca current can be a cause of the elevated tone. Abnormalities in the
      cellular mechanisms for relaxation of the smooth muscle can also contribute to
      the elevation of the active tone. Endothelium suppresses the active tone,
      probably releasing endothelium-derived relaxing factor or hyperpolarizing factor.
      The suppression of contraction by endothelium is impaired in the blood vessels of
      spontaneously hypertensive rats, depending on the degree of hypertension.
      Antihypertensive treatments prevent the development or elevation of the active
      tone. It also prevents the impairment of function of endothelium. Thus, the
      maintained hypertension alters functions of smooth muscle membrane and
      endothelium. The degree and duration of hypertension are thought to be
      determinant factors of these abnormalities.

PMID- 8136559
TI  - Restoration of exocrine pancreatic function following pancreas-liver-kidney
      transplantation in a cystic fibrosis patient.
AB  - Pancreatic transplantation for endocrine replacement is well-established for
      insulin-dependent diabetes mellitus. Exocrine pancreatic function after pancreas
      transplantation has been maintained after orthotopic cluster transplants for
      malignancy, and restoration of adequate exocrine function in a previously
      deficient patient has been reported in a patient with chronic pancreatitis who
      developed labile diabetes and steatorrhea after pancreatectomy. We performed a
      triple organ transplant (pancreas, liver and kidney) in a patient with exocrine
      pancreatic insufficiency and insulin-dependent diabetes related to cystic
      fibrosis (CF) after he developed hepatic and renal failure. Pancreatic exocrine
      secretions were drained enterically to the jejunum. At 24-month follow-up,
      malabsorption is absent. The 3-day stool fat, stool trypsin and chymotrypsin are
      normal. Serum carotene is within the normal range. Exocrine pancreatic
      insufficiency in CF patients can be corrected by pancreas transplantation.
      However, routine use in CF is precluded by the risks of surgery and
      immunosuppression. For diabetic patients with pancreatic exocrine insufficiency
      who require another organ transplant (e.g., lung, liver, or kidney), simultaneous
      pancreas transplantation with the exocrine secretions directed into the upper
      gastrointestinal tract should be considered.

PMID- 8136560
TI  - Use of immune globulin to prevent symptomatic cytomegalovirus disease in
      transplant recipients--a meta-analysis.
AB  - The objective of this meta-analysis was to review the evidence for the use of
      immune globulin in the prevention of symptomatic cytomegalovirus (CMV) disease in
      transplant recipients. A computerized search of Medline from 1980 to October 1991
      was conducted using the textword "cytomegalo:" and the subheading "prevention and
      control" for studies in all languages. Reference lists, a manual search of
      relevant literature and communication with internationally recognized experts
      were used to locate additional studies. Of the studies identified, 18 met the
      inclusion criteria (population: transplant recipients; intervention: immune
      globulin; outcome: symptomatic cytomegalovirus disease; study design: randomized
      controlled trial). The meta-analysis of the 18 studies showed a reduction in the
      incidence of symptomatic CMV disease in the group receiving immune globulin as
      compared to the untreated group. The common odds ratio was 0.58 (95% C.I. 0.42 to
      0.77). Analyses of combining trials by subgroups of polyvalent immune globulin,
      hyperimmune globulin, bone marrow recipients and solid organ recipients resulted
      in common odds ratios comparable to the overall common odds ratio. Common odds
      ratios for the trials reporting cytomegalovirus interstitial pneumonia,
      cytomegalovirus death, overall death and graft loss ranged from 0.47 to 0.69.
      Common odds ratios for the effect of immune globulin prophylaxis analyzed by pre
      transplant patient/donor cytomegalovirus antibody status ranged from 0.32 to
      0.50. In conclusion, the use of immune globulin as passive immunization for the
      prevention of symptomatic cytomegalovirus disease in the transplant population is
      supported by this meta-analysis. The response is similar in both bone marrow and
      solid organ transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136561
TI  - Inferior vena cava obstruction after orthotopic liver transplantation.
AB  - Post-operative inferior vena cava (IVC) obstruction is reported as an uncommon
      complication after orthotopic liver transplantation (OLT). We report 6 cases
      after 245 OLT's in the period between March '79 and December '92. Compression or
      torsion of the IVC or a technical problem were underlying causes. Oligo-anuria
      was observed in almost all patients and was probably caused by renal vein
      hypertension. Doppler ultrasound has become an important tool for the diagnosis
      of this complication. Operative treatment was performed in almost all cases in
      order to correct causative factors. Thrombi above or at the level of the upper
      anastomosis of the IVC should be removed via the right atrium, during cardio
      pulmonary bypass, in order to prevent pulmonary embolism. Thrombi in the IVC
      caudal to the liver can be removed by cavotomy with high positive end expiratory
      pressure ventilation.

PMID- 8136562
TI  - Orthotopic cardiac transplantation for dilated cardiomyopathy after allogeneic
      bone marrow transplantation.
AB  - We report the case of a 26-year-old man with acute myeloid leukemia (AML) who
      underwent bone marrow transplantation (BMT) from an HLA-identical sibling-donor
      when in first complete remission. He developed a dilated cardiomyopathy 9 months
      post-BMT and subsequently underwent orthotopic heart transplantation. He remains
      in complete hematological remission more than 12 months after surgery with normal
      cardiac function and an excellent performance status. Although cardiac
      transplantation has been carried out for chemotherapy-induced cardiomyopathy in
      cancer patients, to our knowledge cardiac transplantation following BMT has not
      been reported previously.

PMID- 8136563
TI  - Intraoperative increment of platelet-activating factor in clinical liver
      transplantation.
AB  - Recent studies have shown that platelet-activating factor (PAF) is involved in
      ischemia/reperfusion injury to the liver. We therefore examined changes in PAF in
      recipients during liver transplantation. The level of PAF increased after portal
      venous reperfusion, except in one case where veno-venous bypass was applied. A
      marked elevation was noted in another case where portal congestion occurred due
      to outflow block, followed by prolonged graft dysfunction. These results suggest
      that elevation of the PAF level is related to portal congestion, and that PAF
      might be involved in postoperative liver graft dysfunction.

PMID- 8136564
TI  - Correlation of serum basic fetoprotein with acute rejection in kidney
      transplantation.
AB  - We monitored serum BFP, a broad-spectrum tumor marker, in 36 patients with kidney
      transplantation. Serum BFP was elevated in close association with acute rejection
      and dropped to a normal level after reversal of rejection. As Western blot
      analysis has revealed that BFP is present in the normal kidney, it is believed
      that serum BFP may be useful for the detection of various types of renal damage
      such as acute rejection.

PMID- 8136565
TI  - Management of the renal allograft recipient: immunosuppressive protocols for long
      term success.
AB  - To determine the benefits of long-term cyclosporine (CsA) immunosuppression,
      renal allograft recipients were randomly assigned to a protocol of either:
      CsA+azathioprine (Aza)+prednisone (TD), or to a protocol in which CsA was
      discontinued from the regimen of Aza+prednisone (CsA D/C). With a mean follow-up
      of nearly 7 years since transplantation, 30/47 (64%) CsA D/C and 27/45 (60%) TD
      had functioning allografts. Although long-term survivals were similar, hazards of
      the CsA D/C protocol were evident (40% rate of acute rejection following CsA
      D/C). Conversely, continued CsA in the TD protocol provided the opportunity for
      prednisone reduction, or even complete prednisone withdrawal in selected
      patients. A TD protocol which can provide equivalent long-term success, and
      eventually lower or omit prednisone, is preferable to a protocol of CsA D/C.

PMID- 8136566
TI  - Successful identification of acute renal allograft rejection with duplex
      ultrasonography.
AB  - Duplex ultrasonography has met with variable accuracy in identifying acute renal
      allograft rejection. These published studies have focused on using mathematical
      indices. We have applied duplex ultrasonography differently by insonating the
      site of rejection, i.e. renal cortex, to identify by subjective analysis the
      changes of the velocity spectral patterns. This subjective analysis method was
      compared to the mathematical indices of diastolic/systolic ratio and pulsatility
      index in 126 episodes of clinical acute renal allograft rejection which all had
      biopsy correlation. This present study represents the largest published
      experience with duplex ultrasonography and renal transplant rejection. Subjective
      analysis of velocity spectral patterns (SUBJ) resulted in sensitivity of 87%,
      specificity of 94% and overall accuracy of 88%. This technique was statistically
      better than the diastolic/systolic ratio (DSR) sensitivity of 40%, specificity of
      72% and overall accuracy of 49%, or the pulsatility index (PI) sensitivity of
      47%, specificity of 75% and overall accuracy of 55%. The superior results of the
      subjective analysis technique of duplex ultrasonography to identify acute renal
      allograft rejection suggests that this diagnostic approach has sufficient
      accuracy to avoid invasive allograft biopsies.

PMID- 8136567
TI  - Recombinant human erythropoietin in renal transplant recipients with renal
      anemia.
AB  - Thirty-seven kidney graft recipients with chronically declining transplant
      function accompanied by renal anemia were treated with recombinant human
      erythropoietin for 3 months. In all these patients anemia improved and mean
      hemoglobin levels increased from 7.67 +/- 1.26 g/dl to 9.83 +/- 1.94 g/dl (p <
      0.01). Mean creatinine increased from 4.23 +/- 1.82 to 4.62 +/- 2.42 (p < 0.05)
      but the progression of transplant failure was not influenced when compared with
      pretreatment values obtained at least 6 months before study entry. Mean blood
      pressure levels were not altered but 12 patients required additional
      antihypertensive medication.

PMID- 8136568
TI  - Early clinical and histologic viability of human liver-small intestinal
      allografts after implantation.
AB  - Our procedure for donor harvesting and preserving intestinal grafts has matured.
      In 27 consecutive cases, a protocol was established whose essentials consist of
      (a) selecting hemodynamically stable donors, (b) antibiotic pretreatment of the
      donor, and (c) short warm ischemic times (< 40 minutes). Assessment of graft
      quality can be achieved by daily inspection of stomas, inspection for diarrhea >
      2.5 1/day in adults or > 300 ml in children, and weekly protocol or clinically
      directed endoscopic biopsies. Edema and microscopic separation of the mucosal
      surface and sloughing are routinely found during the first few post-engraftment
      days, but the crypt cells remain and regenerate a normal mucosa within a week.
      Recovery of a normal mucosal surface took place in all cases.

PMID- 8136569
TI  - Late recurrence of Wegener's granulomatosis presenting as tracheal stenosis in a
      renal transplant patient.
AB  - An unusual case of a 46-year-old man who had end-stage renal disease due to
      crescentic glomerulonephritis that was treated by a cadaveric renal allograft is
      presented. About 18 months post-Tx, the patient developed severe tracheal
      stenosis which, on biopsy, revealed granulation tissue and chronic inflammation.
      After another 18 months he developed necrotizing glomerulonephritis involving the
      renal allograft and an inflammatory retro-orbital pseudotumor. The latter, on
      biopsy, revealed granulomatous vasculitis characteristic of Wegener's
      granulomatosis. This diagnosis was further confirmed by strongly positive anti
      neutrophil antibodies with diffuse granular cytoplasmic immunofluorescence (C
      ANCA). The patient was treated successfully with cyclophosphamide therapy.

PMID- 8136570
TI  - Role of 99mTc-labeled DISIDA scan in the assessment of marginal liver grafts
      after orthotopic transplantation.
AB  - Accurate prognostic indicators are lacking for livers with early marginal graft
      function, making the decision to re-transplant a difficult one. Therefore, we
      studied 99mTc-labeled DISIDA scanning as a predictor of recovery of marginal
      grafts. Records of 28 liver transplant recipients with prolonged periods of
      marginal graft function after liver transplantation were analyzed. Twelve of 28
      (Group I) had delayed PNF and were re-transplanted within 3-8 days (mean 5.3) of
      surgery. The remaining 16 (Group II) recovered slowly, with normal graft function
      at 1 month. All patients received DISIDA scans 2 to 5 d after surgery. Clearance
      of tracer from the blood pool was slower in Group I patients (77S +/- 241 sec)
      than in Group II (260 +/- 38 sec; p < 0.01). Qualitative differences in the
      pattern of parenchymal uptake were also noted. Homogenous uptake, consistent with
      cholestasis, was seen in 15/16 (94%) Group II patients, with improved uptake
      after 7-35 d. In contrast, 11/12 Group I patients had non-homogenous uptake,
      consistent with multiple liver infarctions. This pattern correlated with higher
      peak SGOT in Group I (4358 +/- 658 U/dl vs 1636 +/- 127 U/dl p < 0.01), and PT
      (20 +/- 0.7 sec vs. 16.5 +/- 0.36 sec; p < 0.01). In summary, delays in DISIDA
      tracer clearance from blood, and non-homogenous hepatic uptake correlate with
      elevated liver function tests and with delayed PNF. Homogenous uptake correlates
      with graft recovery. DISIDA scans may, therefore, be useful in predicting
      recovery of marginal grafted livers.

PMID- 8136571
TI  - Monitoring of the cellular immune system in patients with biventricular assist
      devices awaiting cardiac transplantation.
AB  - Lack of objective parameters to predict the clinical course and outcome are a
      major problem in managing the patients selected for BVAD-support as a bridge to
      heart transplantation. This study was intended to assess whether cellular immune
      parameters have a predictive value for the clinical result of VAD-support.
      Various cellular immune markers were monitored by multiparameter cytofluorometry
      in 30 patients who received a VAD system (Berlin Heart). We did not find
      significant differences in preoperative values of immune parameters between
      groups of survivors (n = 14) and non-survivors (n = 16). All 9 patients who died
      of septic multiple organ failure (MOF) had shown increased levels of T-cell
      activation (CD 71, CD 25, HLA-DR) as well as leukocytosis and 7 patients who died
      of noninfectious complications (mostly hemorrhage or cerebral complications) had
      exhibited T-lymphopenia. Seven of 9 patients who died of septic MOF had extremely
      decreased levels of HLA-DR+ monocytes (< 30%) while all 14 survivors and all 7
      patients who died of noninfectious complications showed almost normal monocytic
      HLA-DR antigen expression, antigen-presenting capacity and cytokine secretion.
      These observations point to the reduced antimicrobial immunity
      ("immunoparalysis") in the non-survivors and may explain the fatal course of
      infection in these individuals. The in vitro results of restitution experiments
      call for new therapeutic strategies to improve the survival of VAD-patients.

PMID- 8136572
TI  - Treatment of the Budd-Chiari syndrome with orthotopic liver transplantation and
      long-term anticoagulation.
AB  - The Budd-Chiari syndrome (BCS) with hepatic vein occlusion is a rare disorder
      that can effectively be treated with orthotopic liver transplantation. In this
      retrospective analysis we report on 7 patients who received 9 liver grafts for
      terminal BCS. One patient died after 4 months due to cytomegalovirus-pneumonia.
      The actuarial survival rate is 85.7% compared to more than 90% in all other 376
      patients transplanted between September 1988 and April 1993 at our institution.
      Anticoagulation management consisted of early postoperative intravenous heparin
      and continuation with dicoumarin. One patient with thrombocytosis received
      hydroxyurea. Under this regimen one postoperative hemorrhage requiring laparotomy
      was observed. Discontinuation of oral anticoagulation due to gastrointestinal
      bleeding caused hepatic artery and portal vein thrombosis in 1 patient who had to
      be retransplanted. One recurrence requiring retransplantation as well was due to
      an insufficient dicoumarin intake. In conclusion, terminal BCS represents a good
      indication for orthotopic liver transplantation with a closely-monitored
      anticoagulation to avoid such adverse side effects as thrombosis and hemorrhage.

PMID- 8136573
TI  - Comparison of glucose metabolism and cerebral blood flow during cortical motor
      activation.
AB  - Regions of cerebral cortex activated in normal subjects making simple,
      repetitive, voluntary wrist movements were studied with positron emission
      tomography (PET). The regional cerebral metabolic rate of glucose utilization was
      studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG), and regional cerebral blood
      flow was studied with 15O-labeled water. No significant activation was found with
      the cerebral metabolic rate studies. Studies of regional cerebral blood flow
      showed significant activation of the contralateral sensorimotor cortex region of
      42%, of the ipsilateral sensorimotor cortex region of 19%, and of the medial
      frontal cortex of 30% compared with the resting state. Increases in blood flow in
      the contralateral sensorimotor cortex and medial frontal cortex were visible on
      every activated scan. Measurement of regional cerebral blood flow seems to be
      more sensitive than regional cerebral metabolic rate of glucose utilization for
      studying cortical activation with voluntary movement.

PMID- 8136574
TI  - Unilateral supraclinoid internal carotid artery stenosis with moyamoya-like
      vasculopathy. Noninvasive assessments.
AB  - Presented are the results of an extensive noninvasive assessment of supraclinoid
      internal carotid artery (ICA) stenosis with moyamoya-like vasculopathy in 3
      patients with a history of stroke. Five noninvasive criteria for the diagnosis
      based on magnetic resonance imaging of the brain, and hemodynamic testing using
      ocular pneumoplethysmography, duplex carotid ultrasound, and transcranial Doppler
      sonography were established: (1) normal ocular pneumoplethysmography
      demonstrating no pressure significant stenosis to the level of the ophthalmic
      artery; (2) abnormal Doppler spectral waveforms showing either no flow or a high
      resistance flow pattern for the ipsilateral cervical internal carotid artery; (3)
      paradoxically low flow velocities for the ipsilateral intracranial (ICA) and
      middle cerebral artery (MCA), and markedly abnormal high velocities for the
      contralateral ICA and MCA; (4) decreased ipsilateral MCA vasomotor reactivity;
      and (5) deep MCA territory ipsilateral subcortical watershed infarction evidenced
      by magnetic resonance imaging. This report demonstrates that a noninvasive
      battery of tests may be useful in the early diagnosis and treatment of these
      patients.

PMID- 8136575
TI  - In vivo proton spectroscopy of intracranial infections and neoplasms.
AB  - The chemical characteristics of 10 neoplastic and 11 infectious brain masses were
      studied by in vivo 1H magnetic resonance spectroscopy. In tumors, peak height
      ratios of n-acetyl-L-aspartate to choline were decreased compared to those in
      normal brain tissue and infectious masses (p < 0.02), but the ratios in normal
      brains and those with infections did not differ. N-acetyl-L-aspartate-to
      creatine/phosphocreatine ratios were significantly lower in infectious masses and
      tumors compared to normal brain tissue (p = 0.003). However, in progressive
      multifocal leukoencephalopathy, N-acetyl-L-aspartate appeared relatively
      unchanged. Lactate was greater than choline in 9 of 11 brains with infection, 0
      of 14 control brains, and 1 of 10 tumors. Lactate-to-choline ratios were
      significantly elevated in infectious masses compared with tumors (p < 0.01). 1H
      magnetic resonance spectroscopy is promising for the noninvasive diagnosis of
      focal brain masses.

PMID- 8136576
TI  - Recurrent syncope and quadriplegia.
AB  - A 72-year-old man had posturally induced syncopal episodes, followed by
      quadriparesis, coma, and death. Neuroimaging studies supported the clinical
      diagnosis confirmed by neuropathological findings.

PMID- 8136577
TI  - Neuroimaging studies of cerebral "visceral larva migrans" syndrome.
AB  - "Visceral larva migrans" syndrome is a zoonotic disease caused by the migration
      or presence in human tissue of nematode larva from lower-order animals. This
      syndrome includes generalized illness, eosinophilia, and symptoms arising from
      larval invasions of different organs including the liver, lungs, eyes, and
      central nervous system. There has been only one case report of the computed
      tomographic (CT) and magnetic resonance imaging (MRI) appearances of cerebral
      toxocaral disease. Described here is a patient with cerebral toxocaral disease
      with a high eosinophil count and toxocaral titer in the serum and abnormal CT and
      MRI findings who had spontaneous recovery of the clinical symptoms.

PMID- 8136578
TI  - Magnetic resonance imaging in ochronosis, a rare cause of back pain.
AB  - A 34-year-old man had progressive, poorly controlled low back pain for 3 years
      before testing confirmed a diagnosis of ochronosis. This is the first case
      description of the magnetic resonance imaging (MRI) appearance of spinal
      ochronosis, which should be considered when advanced degenerative change is seen
      on spinal MRI in young individuals.

PMID- 8136579
TI  - Bilateral diabetic thigh muscle infarction.
AB  - A 19-year-old woman with insulin-dependent diabetes mellitus developed pain and
      tenderness in the medial aspect of the left thigh and calf, followed 1 week later
      by similar symptoms in the right leg. Technetium 99m pyrophosphate (PYP)
      radionuclide scans showed increased flow and uptake in the medial thigh muscles.
      Magnetic resonance imaging (MRI) of the thigh showed increased signal on proton
      density and T2-weighted images in the medial and lateral thigh compartments. High
      resolution B-mode ultrasound showed hyperechoic changes in the anteromedial thigh
      muscles, with loss of normal myofascial interfaces, and a mixed appearance,
      bilaterally. Two months later, after the symptoms had begun to resolve, the
      images had improved. This case documents bilateral diabetic thigh infarction
      identified by abnormal technetium 99m PYP flow studies, MRI signal, and B-mode
      ultrasound imaging.

PMID- 8136580
TI  - Clinical recognition of granulomatous angiitis of the brain. Novel magnetic
      resonance image.
AB  - Granulomatous angiitis of the brain is a rare form of vasculitis affecting small
      and medium-size blood vessels. The most common initial symptoms include headache
      and confusion after age 45. The cerebrospinal fluid is almost always abnormal
      with lymphocytic pleocytosis and protein content over 100 micrograms/dl.
      Diagnosis may be supported by contrast-enhanced magnetic resonance imaging
      findings of a hypointense granuloma surrounding a hyperintense blood vessel.
      Described herein is a previously unrecorded magnetic resonance image in an
      autopsied case of granulomatous angiitis of the brain.

PMID- 8136581
TI  - Central pontine myelinolysis with complete recovery.

PMID- 8136582
TI  - Superior sagittal sinus thrombosis in the presence of idiopathic bilateral
      internal jugular vein stenosis.
AB  - Cerebral venous outflow obstruction and anomalies in cerebral venous circulation
      predispose to dural sinus thrombosis. This case report illustrates the magnetic
      resonance and angiographic findings in a patient who had superior sagittal sinus
      thrombosis secondary to idiopathic bilateral internal jugular vein stenosis, a
      previously unrecognized entity. The findings suggest that bilateral stenosis of
      the internal jugular veins at their junction with the innominate veins causes
      obstruction to cerebral venous outflow leading to dural sinus thrombosis.

PMID- 8136583
TI  - 42-year-old woman with a diagnosis of amyotrophic lateral sclerosis (ALS)

PMID- 8136584
TI  - Speech fluency in aphasia. Regional cerebral blood flow correlates of recovery
      using single-photon emission computed tomography.
AB  - This study investigated the relationship between diminished regional cerebral
      blood flow (rCBF) and the recovery of fluent speech in aphasia. Single-photon
      emission computed tomographic brain scans using [123I]N-isopropyl-p
      iodoamphetamine were obtained from 14 nonfluent aphasic patients within 30 days
      of cerebral infarction. Measurements of speech fluency were acquired initially
      and at 3 months after infarction. Nearly all of the patients exhibited
      significant hypoperfusion to combinations of the anterior and posterior regions
      of the basal ganglion, the periventricular white matter, and the inferior frontal
      regions. Only the inferior frontal area was significantly associated with
      recovery of fluent speech. This region was hypoperfused in 4 of 5 patients with
      poor recovery while 8 of the 9 patients with good speech fluency recovery
      demonstrated normal rCBF to the inferior frontal region.

PMID- 8136585
TI  - Treatment of renovascular hypertension with percutaneous transluminal
      angioplasty: experience in Spain.
AB  - PURPOSE: The clinical results of percutaneous transluminal angioplasty (PTA) were
      evaluated in patients with renovascular hypertension, and the effect of PTA on
      blood pressure and renal function was determined. PATIENTS AND METHODS: Between
      February 1982 and December 1990, 93 hypertensive patients underwent 123 renal
      artery PTA procedures. Mean patient age was 43.4 years (range, 12-78 years).
      Average baseline blood pressure was 162/111 mm Hg (range, 140-230/95-150 mm Hg).
      The cause of renovascular hypertension, as determined with angiography, was
      atherosclerosis in 37 patients, fibromuscular dysplasia in 27, and mixed disease
      in one; 28 patients had renal transplant arterial stenosis. RESULTS: In patients
      with atherosclerotic renal vascular disease or fibromuscular renal artery
      stenosis, systolic and diastolic blood pressure decreased significantly (P <
      .001) at 96 months after PTA. In patients with renal transplant arterial
      stenosis, blood pressure also decreased significantly (P < .001) at 12 months
      after PTA. Technical success was achieved in 78% of patients with
      atherosclerosis, 92% of patients with fibromuscular dysplasia, and 76% of
      patients with renal transplants. Complications were seen in 4.8% and were related
      to renal failure and vessel dissection. CONCLUSION: PTA is the therapy of choice
      in patients with renovascular hypertension due to fibromuscular dysplasia.
      Patients with atherosclerotic renal artery stenosis or stenosis of a renal artery
      in a transplanted kidney should be selected according to the anatomy of the
      lesion and clinical patient characteristics.

PMID- 8136586
TI  - Interventional radiologic placement of Hohn central venous catheters: results and
      complications in 100 consecutive patients.
AB  - PURPOSE: Hohn catheters are single- or double-lumen catheters used for
      intermediate-length central venous access. The authors report their technique,
      results, and long-term follow-up in a prospective study of their first 100
      consecutive patients. PATIENTS AND METHODS: Indications for Hohn subclavian
      catheter placement included chemotherapy in 53%, antibiotic therapy in 30%, and
      total parenteral nutrition in 8%. Patients' ages ranged from 21 to 82 years, and
      80% of catheters were placed in inpatients. Hohn catheters were placed with
      fluoroscopic and/or ultrasound guidance. Patients were followed up for the
      duration of the study or until their catheters were removed. RESULTS: The
      technical success rate for catheter placement was 100%. No major procedural
      complications occurred. Duration of catheter placement varied between 5 and 276
      days (mean, 70 days). The catheter infection rate was 8%, which corresponds to
      1.1 infections per 1,000 catheter days. Catheter thrombosis occurred in nine
      cases (9%) and was successfully treated with urokinase in six of these nine.
      Subclavian vein thrombosis occurred in 3% of patients. CONCLUSION: Technical
      success, complication, and long-term patency rates for the Hohn catheter are
      comparable to or better than those in most surgical series involving tunneled
      external catheters. The Hohn catheter is an excellent alternative for
      intermediate-length central venous access. Hohn subclavian catheter placement has
      become a standard part of the authors' interventional radiology service and is
      easily adaptable to all interventional practices.

PMID- 8136587
TI  - Migration of Palmaz stents following deployment for venous stenoses related to
      hemodialysis access.

PMID- 8136588
TI  - Percutaneous transluminal angioplasty of venous anastomotic stenoses complicating
      liver transplantation: intermediate-term results.
AB  - PURPOSE: The authors evaluated the safety and efficacy of percutaneous
      transluminal angioplasty (PTA) for the treatment of venous stenoses in liver
      transplant recipients. PATIENTS AND METHODS: Over a 5-year period, 15 venous
      stenoses were treated with PTA in 12 patients with liver transplants (seven
      children and five adults). PTA was performed for portal vein stenoses in five
      patients, inferior vena cava (IVC) stenoses (n = 6) in five patients, combined
      superior mesenteric vein-portal vein graft anastomosis and hepatic vein-IVC
      anastomosis in one patient, and combined IVC and hepatic vein-IVC anastomosis in
      one patient. PTA was repeated in three patients (five procedures) for recurrent
      IVC stenoses. RESULTS: Initial technical and clinical success of PTA was achieved
      in 11 patients (92%); failure occurred in one patient (8%) with a portal vein
      anastomotic stenosis. No complications occurred in the immediate post-procedure
      period (up to 7 days). Nine patients (75%) are clinically well, with follow-up
      ranging from 7 to 33 months (mean, 18 months). Two of them required one or more
      repeated PTA procedures to maintain vessel patency. One patient required
      retransplantation for chronic rejection at 3 months, and another died of
      gastrointestinal tract bleeding from a gastric ulcer at 2 months after initially
      successful IVC PTA. CONCLUSIONS: PTA is a safe procedure for the treatment of
      venous anastomotic stenoses in liver transplant recipients. PTA of portal vein
      anastomotic stenosis has favorable intermediate-term results. Repeat PTA may be
      necessary in some cases of IVC anastomotic stenoses to maintain vessel patency
      and avoid surgical revision or retransplantation.

PMID- 8136589
TI  - Cystic duct remnant mucocele in a liver transplant recipient.

PMID- 8136590
TI  - Percutaneous embolotherapy of adolescent varicocele: results and long-term follow
      up.
AB  - PURPOSE: The authors evaluated the technical success and immediate and long-term
      results of percutaneous varicocele embolotherapy in the adolescent population.
      PATIENTS AND METHODS: Fifty-nine adolescent patients were referred for outpatient
      spermatic venography and possible varicocele embolotherapy. Embolization was
      attempted with use of detachable balloons, coils, "sandwiched" dextrose, or a
      combination of these techniques. Data regarding follow-up were obtained through
      telephone interviews or mailed questionnaires. RESULTS: The technical success
      rate for spermatic vein occlusion was 90%. Follow-up, obtained in 79% of the
      patients, ranged from 6 months to 8.75 years (mean, 4 years). Thirty-nine of 42
      patients (93%) reported disappearance (n = 31) or only a slight, asymptomatic
      residual varicocele (n = 8). Three patients reported a recurrence of their
      varicocele. Complications occurred in three of 59 cases (5%), none had any long
      term sequelae. In six cases, embolization was not feasible because of multiple
      collateral vessels or venous spasm. CONCLUSIONS: Given the convenience of
      performing the procedure on an outpatient basis, the rapid recovery time, and
      long-term success and complication rates comparable to those with surgical
      ligation, we believe spermatic venography and percutaneous embolization is the
      treatment modality of choice for adolescent varicocele.

PMID- 8136591
TI  - Emergency percutaneous nephrostomy: results and complications.
AB  - PURPOSE: Percutaneous nephrostomy is a well-established standardized procedure in
      the management of patients with various urologic problems. The goal of this study
      was to evaluate the effectiveness and safety of percutaneous nephrostomy in an
      emergency setting. PATIENTS AND METHODS: Emergency percutaneous nephrostomy was
      performed in 160 patients with ages ranging from 2 to 89 years (mean, 52 years).
      Access to the kidney was planned and achieved with C-arm fluoroscopic guidance.
      RESULTS: The initial technical success rate was 98%. Overall complication rate
      was 34%; 6% were major and 28% were minor. Major procedure-related complications,
      including sepsis, occurred in 6% of patients. Hematuria requiring transfusion was
      noted in 2.4% of patients. Minor complications included catheter displacement or
      malposition (4.8%), pelvic perforation (4.3%), paralytic ileus (2.4%),
      pneumonia/atelectasis (1.8%), and pleural effusion (1.2%). High-risk patients
      included those with diabetes, hypertension, and obesity. No deaths or significant
      morbidity resulted from any complication. CONCLUSIONS: Emergency percutaneous
      nephrostomy under fluoroscopic guidance is a simple, safe, and effective
      procedure and should be offered in all suitably equipped radiology departments.

PMID- 8136592
TI  - Venous valvular incompetence of the upper extremity.

PMID- 8136593
TI  - Air along new polytetrafluoroethylene grafts: inability to demonstrate flow with
      Doppler sonography.

PMID- 8136594
TI  - Hemorrhage from spontaneous rupture of muscular branches of the superficial
      femoral artery.

PMID- 8136595
TI  - Short-term effects of selective renal arterial carbon dioxide administration on
      the dog kidney.
AB  - PURPOSE: The authors examined the nephrotoxicity of carbon dioxide injected
      directly into the renal arteries as an arterial contrast agent. MATERIALS AND
      METHODS: Fourteen anesthetized dogs received selective renal infusions of CO2
      ranging from a normal dose of 7 cm3/kg to high doses of 11-54 cm3/kg. Two dogs
      received conventional iodinated contrast media. The effects on renal function and
      histologic appearance were evaluated by means of radionuclide studies (iodine-131
      iodohippurate sodium and technetium-99m dimercaptosuccinate) and histopathologic
      examination (light, transmission, and scanning electron microscopy). RESULTS:
      Although there was a mean decrease in renal blood flow of 11.86% (standard error
      [SE], 7.1) immediately after the injection of CO2, flow had returned to baseline
      (0.17%; SE, 5.27) after 24 hours. Although the sample size was small, there was
      no dose-dependent effect of CO2 on renal function and histologic appearance. Mild
      histologic changes and one case of moderate acute tubular necrosis were seen only
      in cases in which the kidney was positioned vertically rather than laterally.
      CONCLUSION: Although formal studies in patients are required, the results of this
      investigation suggest that CO2 may be a safe contrast agent and less nephrotoxic
      than existing contrast agents, providing care is taken to ensure that CO2 is not
      trapped in a vertically positioned kidney, as might occur in renal transplant
      recipients.

PMID- 8136596
TI  - Hemolytic effect of the Amplatz thrombectomy device.
AB  - PURPOSE: The hemolytic effect of the Amplatz thrombectomy device (ATD) was
      evaluated in nine dogs and in nine patients. MATERIALS AND METHODS: The device
      was activated for 1-2 minutes in the abdominal aorta, inferior vena cava, or
      femoral artery of nine dogs. The device was activated for 1-4 minutes in the nine
      patients in occluded lower extremity bypass grafts (n = 5), native superficial
      femoral artery (n = 1), a pulmonary artery embolus (n = 1), a portocaval shunt (n
      = 1), and an iliac vein stent (n = 1). Patients were examined for laboratory
      evidence of hemolysis following mechanical thrombectomy. RESULTS: In all dogs
      haptoglobin level decreased, free hemoglobin level in the plasma increased, and
      hemoglobinuria was present. There was no change in renal function. The level of
      haptoglobin decreased and the level of plasma free hemoglobin increased in eight
      patients, with hemoglobinuria detected in one. More hemolysis was observed in the
      animals than in the patients. CONCLUSION: The ATD has a definite transient
      hemolytic effect. Until further studied, it should not be used in children and
      should be used with caution in patients who are anemic, hypoxemic, or have
      potentially reversible renal insufficiency. Activation time should be monitored
      closely because hemolysis probably increases with increasing activation time.

PMID- 8136597
TI  - Fluoroscopically guided peritoneal catheter placement for intraperitoneal
      chemotherapy.
AB  - PURPOSE: Surgical placement of intraperitoneal catheters for intraperitoneal
      chemotherapy is associated with bowel perforation, peritonitis, and catheter
      occlusion. The authors evaluated the safety and efficacy of fluoroscopically
      guided placement of temporary intraperitoneal catheters for chemotherapy.
      PATIENTS AND METHODS: Two hundred one intraperitoneal catheter placements were
      attempted in 88 patients with peritoneal carcinomatosis or sarcomatosis. The
      peritoneum was punctured with 22-gauge needles and exchange was made with use of
      Seldinger technique and liberal injections of contrast material at each step for
      8.3- or 8.5-F multiple-side-hole catheters. Placement sites included all four
      quadrants and the midline. Computed tomographic (CT) peritoneography was
      performed prior to chemotherapy. RESULTS: One hundred ninety (94.5%) of 201
      attempted catheter insertions were technically successful. Results of CT
      peritoneography were available in 175 cases and showed free distribution of
      peritoneal contrast material in 39% (n = 69), partial loculation in 38% (n = 67),
      and extensive loculation in 22% (n = 39). Catheters remained in place for a
      median of 5 days (range, 2-6 days). Significant complications occurred in 11
      procedures (5.5%). There were seven unintended bowel intubations; all were
      treated conservatively except one that required surgical repair. One other
      patient developed necrotizing fasciitis requiring surgical debridement. Three
      other patients (1.5%) developed mild peritonitis responsive to antibiotics.
      Technical success, complications, and peritoneal distribution of contrast
      material did not correlate with the site of catheter placement. CONCLUSION:
      Percutaneous catheter placement with use of small-gauge needles for initial
      puncture is safe and efficacious in patients requiring short-term peritoneal
      access for chemotherapy.

PMID- 8136598
TI  - Clostridial bacteremia and death following chemoembolization for hepatocellular
      carcinoma.

PMID- 8136599
TI  - Reducing the discomfort of lidocaine administration through pH buffering.
AB  - PURPOSE: A prospective, double-blind study was undertaken to evaluate the effect
      of using a buffered lidocaine solution on the perception of pain experienced by a
      patient during its intradermal injection. PATIENTS AND METHODS: One hundred fifty
      patients undergoing diagnostic angiographic and interventional procedures at the
      authors' institution were randomly assigned to receive a 1-mL aliquot of one of
      three lidocaine solutions: plain 1% lidocaine, 1% lidocaine diluted with normal
      saline in a 10:1 ratio, and 1% lidocaine diluted with 8.4% sodium bicarbonate in
      a 10:1 ratio. The lidocaine solutions were administered intradermally over 10-15
      seconds. A numerical value was placed on the patient's perception of pain,
      separate from that associated with the 25-gauge needle insertion, with use of a
      linear visual analog scale. RESULTS: Mean pain scores were as follows: for the 1%
      lidocaine solution, 2.83 +/- 2.60; for 1% lidocaine plus normal saline solution,
      2.89 +/- 2.34; and for 1% lidocaine plus sodium bicarbonate solution, 1.37 +/-
      1.73 (P = .0018). CONCLUSION: Buffering lidocaine significantly decreased the
      discomfort associated with its administration as a local anesthetic.

PMID- 8136600
TI  - Fatal reexpansion pulmonary edema following pleural catheter placement.

PMID- 8136601
TI  - Potential biological effects following high X-ray dose interventional procedures.
AB  - Some interventional procedures can result in very high x-ray doses. Potential
      biological effects of high x-ray doses are reviewed. Deterministic and stochastic
      effects in skin, bone, parotid glands, and lung are discussed. Threshold doses
      for the effects and relevant dosimetric principles are addressed. General
      principles for minimizing the potential for these effects are presented.
      Knowledge about these effects and the means to minimize radiation dose can assist
      the physician in the care of patients undergoing lengthy invasive radiologic
      procedures.

PMID- 8136602
TI  - Endovascular credentialing.

PMID- 8136603
TI  - Percutaneous intraarterial thrombolysis: analysis of factors affecting outcome.
AB  - PURPOSE: The authors report results of high-dose thrombolytic therapy in native
      arteries and vein grafts and discuss the various factors affecting outcome.
      PATIENTS AND METHODS: In a retrospective study, the outcome of 82 high-dose
      urokinase infusions in 76 patients was examined. Comorbid risk factors as they
      relate to outcome were studied extensively with log-linear analysis. Positive
      thrombolytic outcome (PTO) is defined as complete thrombolysis of a previously
      occluded segment with restoration of antegrade flow augmented by angioplasty or
      operative intervention to clear symptoms for 30 days. RESULTS: The procedure
      resulted in a PTO in 63 of 82 instances (77%). The treatment was with urokinase
      alone in 39 cases (47%) and urokinase followed by surgery in 34 (41%), by
      angioplasty in four (5%), and by angioplasty in the proximal artery and
      peripheral vein grafting in five (6%). All stenoses associated with grafts were
      treated surgically. None of the following affected thrombolytic outcome: age of
      occlusion, heparin dose, catheter type, length or location of graft, or artery
      versus graft occlusion. The 30-day mortality was 6.1%, with a procedure-related
      mortality rate of 2.4%. Overall amputation rate was 18% (74% for patients in whom
      lysis failed by 30 days). CONCLUSION: The presence of at least one runoff vessel
      was the most important factor affecting outcome (PTO, 95%; P = .00001, chi 2).
      The most important comorbid risk factor for failed thrombolysis was coronary
      artery disease (P = .03, chi 2).

PMID- 8136604
TI  - The efficacy of leukodepletion to improve platelet transfusion response: a
      critical appraisal of clinical studies.

PMID- 8136605
TI  - In vitro assessment of the quality of stored platelet concentrates. The BEST
      (Biomedical Excellence for Safer Transfusion) Task Force of the International
      Society of Blood Transfusion.

PMID- 8136606
TI  - The role of platelet microparticles in hemostasis.

PMID- 8136607
TI  - The immunogenetics of bone marrow transplantation.
AB  - It is now clear that it is not necessary to use an HLA genotypically identical
      donor to have a successful marrow transplant. However, it is equally clear that
      the likelihood of complications increases with each increment in
      histoincompatibility. The implication is that histocompatibility testing must be
      of the highest possible precision to choose the optimal donor, and to predict the
      risk of adverse alloreactivity. Most clinicians would seriously consider
      transplantation from a one locus-mismatched relative or an HLA-matched unrelated
      donor in virtually any situation in which transplantation from a matched sibling
      would be felt to be the standard of care. More thought would need to go into
      transplantation from a two or three locus-mismatched relative or a mismatched
      unrelated donor.

PMID- 8136608
TI  - The use of monoclonal antibodies and immune markers in the diagnosis, prognosis,
      and therapy of acute leukemia.

PMID- 8136609
TI  - HIV transmission in the provision of health care.

PMID- 8136610
TI  - Problems with the interpretation of gastric pH measurement.
AB  - The present study examines some of the assumptions underlying the use of
      intragastric pH-metry for assessing the degree of therapeutic gastric inhibition.
      Three separate studies were performed to determine the relationship between pH
      and titratable hydrogen ion concentration in gastric juice and to assess the
      relationship between the concentration of acid and the rate of gastric secretion.
      The concentration of acid derived from pH measurements tended to be lower than
      the titrated hydrogen ion concentration. The difference between the two readings-
      the "buffered" hydrogen ion concentration--was increased by the presence of food
      and was reduced during gastric secretory inhibition with ranitidine. The titrated
      hydrogen ion concentration reflected more accurately the amount of hydrochloric
      acid added to a container in vitro than pH measurement. However, in vivo even the
      measurement of titratable acidity was poorly correlated with the volume of
      secreted gastric juice so that measurement of gastric acid concentration does not
      permit inferences about the rate of gastric secretion. The results of the present
      study indicate that measurement of intragastric pH is unsatisfactory for
      assessing gastric secretion, particularly in response to a food stimulus, so that
      measurement of gastric acidity alone does not reflect the rate, or changes in the
      rate, of gastric acid secretion.

PMID- 8136611
TI  - Increased fMet-Leu-Phe receptor expression and altered superoxide production of
      neutrophil granulocytes in septic and posttraumatic patients.
AB  - Activation of neutrophils by various inflammatory stimuli has been shown to play
      a pivotal role in septic and posttraumatic tissue injury. To further elucidate
      the mechanisms modulating the oxidative metabolism, we assessed superoxide
      production induced by N-formylmethionyl-leucyl-phenylalanine (FMLP) and phorbol
      myristate acetate and the expression of FMLP receptors of human neutrophils on
      several days during sepsis and after trauma. Neutrophils of septic patients
      isolated on days 0-4 after the diagnosis of sepsis showed a significant, more
      than twofold increase in specific binding of [3H]FMLP at 1, 120, and 240 nM.
      Scatchard plot analyses revealed that this increase in specific binding was due
      to an increase in the number of low- and high-affinity FMLP receptors with no
      changes in receptor affinity. On days 5-10 after the onset of sepsis the up
      regulation of FMLP receptors on circulating neutrophils was followed by receptor
      down-regulation. Likewise, neutrophils from patients with trauma that was not
      complicated by sepsis bound significantly more [3H]FMLP than neutrophils from
      volunteers. However, the increase in FMLP receptors was less than that in septic
      neutrophils and returned earlier to normal. In accordance with the up-regulation
      of FMLP receptors, neutrophils obtained from patients with sepsis or after trauma
      on days 1-4 and days 1-2, respectively, produced significantly more superoxide
      anion upon stimulation with FMLP. However, after stimulation with phorbol
      myristate acetate, a receptor-independent activator of protein kinase C, these
      cells released less superoxide anion than controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8136612
TI  - Evaluation of increased serum ferritin levels in patients with hyperthyroidism.
AB  - To further elucidate the mechanism of increased serum ferritin levels in
      hyperthyroidism, the changes in erythrocytes and serum iron and total iron
      binding capacity levels were examined in addition to serum ferritin levels in 13
      hyperthyroid patients. The mean values of hemoglobin, red blood cells, and packed
      cell volume were increased by antithyroid therapy. While the serum levels of iron
      did not change, those of total iron-binding capacity increased significantly
      after achieving a euthyroid state. Increased serum ferritin levels returned to
      normal through antithyroid therapy. Furthermore, the serum ferritin levels of
      four anemic patients were significantly higher than those of nine nonanemic
      patients. Thus it is concluded that the increase in serum ferritin levels in
      patients with hyperthyroidism may be due to the direct action of thyroid hormones
      on its synthesis, while in some cases complicated with anemia impaired iron
      utilization by erythropoietic cells may also be involved.

PMID- 8136613
TI  - Neutrophilic migration through capillarylike micropores: influence of pulmonary
      passage.
AB  - We report the effect of pulmonary passage on random migration and chemokinesis of
      neutrophils through capillarylike pores under the in vitro condition of Boyden's
      test. Neutrophils were isolated either from the left ventricle or from the
      pulmonary artery of patients who underwent coronary angiography due to suspected
      angina pectoris or valvular heart disease. In all 14 cases left ventricle
      neutrophils showed significantly enhanced chemotactic-activated migration
      compared with pulmonary artery neutrophils. Pulmonary passage also influenced the
      random migration of neutrophils, except for those derived from five patients
      suffering from pulmonary hypertension. Our findings might indicate that
      accumulation of neutrophils in the capillaries of the normal lung is counteracted
      by a change in neutrophilic migration behavior during pulmonary passage, thus
      avoiding increased neutrophilic sequestration in pulmonary microcirculation as
      observed in adult respiratory distress syndrome.

PMID- 8136614
TI  - Glycocholic acid in chronic active hepatitis and mild liver diseases.
AB  - Serum levels of fasting glycocholic acid were measured in various noncirrhotic
      liver diseases. Forty-five patients were evaluated, 15 with chronic active
      hepatitis and 30 with mild liver diseases including chronic persistent hepatitis,
      steatosis, and minimal changes. There were increased levels of glycocholic acid
      in 53.3% of chronic active hepatitis cases and in 10% of mile liver disease cases
      (P = 0.003), and the levels reached by patients with chronic active hepatitis
      were higher than those in patients with mild liver disease (P < 0.0001). The
      latter did not show significant differences in their serum levels or in the
      percentage of abnormal results with respect to control group. There were weak,
      although significant, correlations between glycocholic acid and transaminases,
      alkaline phosphatase, gamma-glutamyltranspeptidase, albumin, and gammaglobulin.
      In the present study, the specificity of glycocholic acid was high in the
      detection of chronic active hepatitis patients at different cut-off levels.
      Glycocholic acid appeared to reflect histological severity in this group of
      noncirrhotic liver diseases and might have practical applications in the
      management of these patients.

PMID- 8136615
TI  - The acquired hyperostosis syndrome: a little known skeletal disorder with
      distinctive radiological and clinical features.
AB  - The acquired hyperostosis syndrome (AHS) is a chronic inflammatory disorder of
      bone of unknown etiology. It is accompanied by circumscribed hyperostosis which
      can be associated with ossifying lesions at sites of tendinous and ligamentary
      insertions and erosive or non-erosive arthritis. The predominant location of
      lesions is the sternocostoclavicular region (approximately 80% of patients), less
      frequent are involvement of the spine, pelvis, and appendicular skeleton. In 20%
      60% of cases AHS is associated with palmoplantar pustulosis, psoriasis, or severe
      acne (acne fulminans or conglobata). The X-ray appearance of AHS is a more or
      less homogeneous increase in density with blurred margins, which on scintiscan
      with labeled phosphate compounds is associated with intense accretion of tracer.
      These features are associated with a variable increase in the acute phase
      reactants and a conspicuously low increase, if any, in serum alkaline
      phosphatase. The therapeutic modalities which have been used so far are entirely
      symptomatic. Long-lasting improvement has been reported following percutaneous
      anti-inflammatory radiation therapy.

PMID- 8136616
TI  - Thrombectomy with arteriovenous fistula for embolizing deep venous thrombosis: an
      alternative therapy for prevention of recurrent pulmonary embolism.
AB  - Thrombectomy with arteriovenous fistula was performed between 1977 and 1988 in
      103 patients (41 females, 62 males, mean age 46.7 years, 114 involved
      extremities) with embolizing deep-vein thrombosis (DVT). The sole aim of the
      surgical procedure was prevention of recurrent embolization. On the basis of the
      proximal extent of the thrombosis the source of embolization was identified as
      the iliac veins or inferior vena cava in 63% of the patients; 48% presented with
      a post-phlebitic vein and/or an older thrombosis, and 46% had already had
      recurrent pulmonary emboli. Unsuccessful aggressive procedures had been carried
      out previously in 11%. The rate of intraoperative pulmonary embolism (PE) was 3%
      (one fatal case). The perioperative mortality was 6.8%, but only one death was
      related to the surgical treatment itself. During follow-up (8-140 months
      postoperatively, mean 55 +/- 34 months) late recurrent PE was confirmed in two
      patients (antithrombin III deficiency, contralateral DVT) and was reported as the
      suspected cause of death in a third (3.6%). Venous thrombectomy with
      arteriovenous fistula is a reliable and effective procedure for management of
      embolizing DVT and is indicated especially in young patients. The rates of early-
      and late-recurrent PE are low, introduction of artificial material into the vein
      can be avoided, and long-term preservation of valve function is occasionally
      possible.

PMID- 8136617
TI  - Deposits of paraprotein in small vessels as a cause of skin ulcers in
      Waldenstrom's macroglobulinemia.
AB  - A 71-year-old man presented with epistaxis and large ulcers on arms and legs. A
      monoclonal IgM-kappa gammopathy and high levels of cryoglobulins were found.
      Histology of the affected skin showed deposits of paraprotein in the small
      vessels, causing luminal obstruction. This in turn caused ischemic skin lesions,
      which were successfully treated with cortisone (fluocortolone 100 mg/day every
      second day) and cyclophosphamide (100 mg/day).

PMID- 8136618
TI  - Bacillary angiomatosis in a German patient with AIDS.
AB  - A 52-year old male homosexual patient with acquired immunodeficiency syndrome
      (AIDS) presented in our clinic with multiple nodular papules (more than 100)
      spread over the whole body which had developed within 3 months. Bacillary
      angiomatosis was suspected, which is a bacterial infectious disease recognized
      recently mainly in patients with AIDS. Histological and immunohistochemical
      examinations of extirpated skin lesions were in agreement with the diagnosis, and
      the detection of rod-shaped bacteria in the lesions by Warthin-Starry silver
      stain confirmed it. The patient was treated with 2 x 100 mg doxycycline per day.
      The fever disappeared, and the cutaneous lesions showed a slight tendency to
      improve. However, after 5 days of therapy the patient showed increasing weakness,
      with muscle and bone pain. The patient died 10 days after the doxycycline therapy
      had been started. The cutaneous lesions in bacillary angiomatosis may resemble
      Kaposi's sarcoma and may therefore be misdiagnosed. The disease may be fatal, but
      timely antibiotic treatment is usually effective; therefore, the diagnosis of
      bacillary angiomatosis is important. Although many cases have been reported from
      the United States, only one case is known from Europe. Our finding of bacillary
      angiomatosis in a German AIDS patient supports the concept of a worldwide
      distribution of this bacterial agent.

PMID- 8136619
TI  - Alpha 1-adrenoceptors in the human prostatic urethra are different from those of
      the human peripheral arteries.

PMID- 8136620
TI  - Hypothalamic-pituitary activation does not differ during human and porcine
      insulin-induced hypoglycemia in insulin-dependent diabetes mellitus.
AB  - Although pituitary hormones play only a minor role in acute hormonal
      counterregulation during insulin-induced hypoglycemia, their concomitant
      secretion with the profound sympathoadrenal response provides an indicator of
      hypothalamic-pituitary activation. The release of different amounts of beta
      endorphin, growth hormone, and adrenocorticotropin during human (HI) and porcine
      (PI) insulin-induced hypoglycemia would serve as a pointer to a different insulin
      species effect on hypothalamic-pituitary response. We performed a controlled,
      double-blind study with randomization to either HI or PI to compare insulin
      effects during developing and established hypoglycemia. The glucose clamp
      technique was used to lower the blood glucose concentration stepwise (3.3, 2.2,
      1.7 mmol/l) over similar periods in ten patients with insulin-dependent diabetes
      mellitus. beta-endorphin, growth hormone, and adrenocorticotropin levels were
      determined by radioimmunoassay from arterialized blood at the above plateaus. A
      different action of HI or PI on peripheral glucose metabolism was not found.
      Pituitary hormones increased significantly during hypoglycemia (analysis of
      variance for hypoglycemic effects: beta-endorphin, P < 0.02; growth hormone, P <
      0.04; adrenocorticotropin, P < 0.05). No insulin species effect was detected.
      Hypothalamic-pituitary activation during insulin-induced hypoglycemia is
      independent of the insulin species used, which supports earlier observations of
      an identical sympathoadrenal response during HI- and PI-induced hypoglycemia.

PMID- 8136622
TI  - Self-medication for abdominal discomfort resulting in life-threatening
      consequences.

PMID- 8136621
TI  - Depression by nicotine of pain-related nociceptive activity in the rat thalamus
      and spinal cord.
AB  - To assess the possible role of nicotinergic control in nociception and pain,
      experiments were carried out on rats under urethane anesthesia in which
      nociceptive activity was elicited by electrical stimulation of afferent C fibers
      in the sural nerve and recorded from single neurones in the thalamus and from
      ascending axons in the spinal cord. Intravenous administration of nicotine (0.01
      0.5 mg/kg) depressed the nociceptive activity evoked in the thalamus and the
      spinal cord in a dose-dependent way. The maximum depression in thalamus and
      spinal cord was 40% of control activity and obtained at a dose of 0.025 mg/kg.
      Likewise, local administration of nicotine to the spinal cord by intrathecal
      injection (5, 10, and 30 micrograms) reduced the nociceptive activity evoked in
      neurones of the thalamus and in ascending axons of the spinal cord, the maximum
      of the depression being 40% of control activity. The depressant effect of
      nicotine (0.05 mg/kg) was reduced by mecamylamine (1 mg/kg) but not by atropine
      (0.5 mg/kg). It is concluded that the antinociceptive effect of nicotine is due
      to a specific action of the alcaloid at the spinal level.

PMID- 8136623
TI  - Dependence on tramadol.

PMID- 8136625
TI  - Nursing implications of low-dose heparin to infusate to improve infusion site
      survival in children.
AB  - Initiation of intravenous (i.v.) infusions in hospital wards is a common surgical
      procedure. Unfortunately many of these infusions will fail due to phlebitis
      and/or extravasation. Such failure may cause considerable patient discomfort,
      interfere with i.v. therapy and increase the nurse's workload. I.v. problems with
      adults have been evaluated extensively, however little attention has been given
      to children. Heparin is effective in reducing thrombus formation and studies have
      demonstrated other properties as well, such as anti-inflammatory, anti-irritant,
      maintenance of endothelial integrity and homeostasis, and tissue healing. The
      purpose of this study was to determine if the addition of low-dose heparin to
      infusate would prolong infusion site survival in children. An experimental design
      was used whereby patients were randomly allocated into control and treatment
      groups. The treatment group received pre-mixed fluids containing 1 unit/ml of
      heparin whilst the control group received standard fluids. Data were collected
      using a standard form and information such as type and size of cannula, sex, age,
      date and time of cannulation, site, signs of phlebitis/extravasation, reasons for
      cannula removal and type of fluids and drugs infused, were recorded. Failure
      incidence was analysed by Cox's multivariate hazards model, life-table method and
      log rank tests. The results showed a highly significant difference (Chi 2 20.42,
      p < 0.0001) in decreasing infusion failure with the addition of low-dose heparin
      to infusate. Nursing implications could include a decrease in the incidence of
      extravasation and phlebitis, an increase in effective vein usage, fewer problems
      with i.v. flow rates, a reduction in medical/nursing hours associated with re
      cannulations, less likelihood of systemic sepsis, and less patient worry and
      discomfort due to local venous reactions and re-cannulations.

PMID- 8136624
TI  - Biochemical evidence for heterozygosity in muscular carnitine
      palmitoyltransferase deficiency.
AB  - Carnitine palmitoyltransferase (CPT) was studied in muscle homogenates of four
      patients with recurrent attacks of rhabdomyolysis due to muscular CPT deficiency
      and in those of the clinically asymptomatic father and mother of two patients. In
      controls CPT II was readily solubilized by the addition of Triton X-100 and 1%
      Tween 20. In contrast, CPT I was inactivated by Triton X-100 but remained
      catalytically active and membrane bound in the presence of 1% Tween 20. Total CPT
      activity was normal in patients and in both parents when measured under optimal
      assay conditions. After addition of 1% Tween 20 the insoluble CPT activity was
      also normal in patients and in both parents. The soluble CPT activity, however,
      was almost completely lost in patients but was only partially decreased in both
      parents. The data indicate that in patients an enzymatically active CPT II exists
      which is abnormally sensitive to inhibition by Tween 20, and that CPT I activity
      is not compensatorily increased in patients. A partial CPT II deficiency can be
      identified in heterozygotes most sensitively by the separate determination of
      soluble and insoluble CPT activities in the presence of 1% Tween 20.

PMID- 8136626
TI  - Guide for viewing a chest X-ray.

PMID- 8136627
TI  - Dunedin-New Zealand, 17-21 August 1993. Report on the annual meeting of the
      Australasian Neuroscience Nurses Association and the Neurosurgical Society of
      Australasia.

PMID- 8136628
TI  - Perth-Western Australia, 28-31 October 1993. Report on the 18th Australian & New
      Zealand scientific meeting on intensive care.

PMID- 8136629
TI  - Why it is important for nurses to do research.

PMID- 8136630
TI  - Education for Queensland nurses has undergone considerable change.

PMID- 8136631
TI  - Health assessment and the nursing process: a means to an end?
AB  - The content and process of teaching health assessment coupled with the nursing
      process gathers momentum because it is consistent with health policy based on the
      principles of economic rationalism, and it covertly perpetuates positivist
      medical discourse while overtly postulating the emancipatory nature of adopting
      such practices.

PMID- 8136632
TI  - An interpretative study of the clinical practice of critical care nurses.
AB  - This study explores the nature of clinical practice of eight expert nurses
      working in an intensive care unit. It is ontological and epistemologically
      grounded in Heideggerian phenomenological hermeneutics. This paper provides a
      description of the relevant Heideggerian concepts, in particular worldliness,
      understanding and care. The hermeneutic analysis revealed four themes: being
      busy, comforting, focusing and balancing. The paper concludes by discussing some
      ontological qualities, from a Heideggerian perspective, that underpin critical
      care nursing practice. This study contributes to the endeavour of exploring
      alternative ways of investigating human experience and also attempts to provide
      insight into the lifeworld of expert nurses working in an intensive care unit.
      The specific purpose of the study was to provide a phenomenological hermeneutic
      analysis of the aesthetics of nursing practice in an intensive care unit.
      Consistent with the epistemology of phenomenological hermeneutic philosophy, I
      have chosen to use the first person in reporting these research findings (see
      Webb 1992 for further discussion).

PMID- 8136633
TI  - The nursing process: a step forward?
AB  - The nursing process provides a framework for nursing practice. Nursing literature
      however, highlights that both nurses and patients may experience problems
      associated with its use. The nursing process may not be the best method of
      delivering holistic nursing care.

PMID- 8136634
TI  - Nursing practice: tomorrow's solutions today.

PMID- 8136635
TI  - Closing the communication gap.

PMID- 8136636
TI  - Don't be afraid to trust your intuition.

PMID- 8136637
TI  - Childhood immunization, homoeopathy and community nurses.
AB  - The way for community nurse practitioners to promote medical childhood
      immunization to parents, is for them to become fully conversant with both
      alternative and traditional medical approaches to this issue. A brief overview of
      homoeopathy and its approaches to immunization is outlined highlighting the
      current debate for and against anti-medical and medical immunization. Arguments
      are put forward supporting medical immunization and the challenges this presents
      for nurses practitioners.

PMID- 8136638
TI  - A call for subjectivity in nursing documentation.

PMID- 8136639
TI  - Nursing assessment: more than merely 'doing the obs'.

PMID- 8136640
TI  - The debate that surrounds the Consent to Medical Treatment and Palliative Care
      Bill.

PMID- 8136641
TI  - The use of relaxation for the promotion of comfort and pain relief in persons
      with advanced cancer.
AB  - The efficacy of a relaxation technique involving deep breathing, muscle
      relaxation, and imagery was tested as a nursing intervention for the promotion of
      comfort and pain relief in hospitalized oncology patients. The intervention was
      implemented in accordance with Orem's self-care approach to nursing practice.
      Sixty-seven new admissions to an oncology ward were randomly assigned to receive
      relaxation training by audio tapes, live relaxation training by nurses, or no
      relaxation training. Relaxation training was conducted twice weekly over a period
      of three weeks. All subjects were pretested and post-tested with the McGill Pain
      Questionnaire and Visual Analogue Scale for pain. Analgesic medication was
      monitored throughout the study. Data analysis showed significant reductions in
      subjective pain ratings by subjects receiving relaxation training. There was also
      a significant reduction in non-opiate p.r.n. analgesic intake which suggested a
      reduced incidence of breakthrough pain.

PMID- 8136642
TI  - [Xianbai buyang Huanwu decoction used for treating hypertension with kidney qi
      deficiency and blood stasis].
AB  - 80 patients of presenium hypertension with geriatric Kidney Qi Deficiency and
      Blood Stasis were randomly divided into two groups. (1) Traditional Chinese
      Medicine group (TCMG, 50 cases) treated with Xianbai Buyang Huanwu Decoction
      (XBH); (2) Western medicine group (WMG, 30 cases) treated with compound
      hypotensor tablets and gamma-evening primrose-E oil capsules. RESULTS: The
      difference between the two groups was not significant (P > 0.05). After
      treatment, in TCMG, serum cholesterol and triglyceride, fibrinogen, whole blood
      viscosity and plasma viscosity, plasma and erythrocyte LPO activity lowered
      significantly, and plasma SOD and erythrocyte SOD raised significantly (P < 0.001
      0.05), while in WMG, only showed the plasma LPO dropped (P < 0.05). The results
      suggested that XBH has the effects of reducing blood pressure, lowering the blood
      lipid, improving hemorrheological parameters and antioxidation.

PMID- 8136643
TI  - [Relation between traditional Chinese medicinal syndrome differentiation and
      blood platelet function in 310 cases of blood stasis].
AB  - 310 patients (153 male, 157 female) of Blood Stasis were divided into various
      groups by Syndrome Differentiation of TCM and 35 healthy subjects were taken as
      control. The relationship of TCM Syndrome and function of blood platelet were
      studied with blood platelet counting, its volume, adherence and aggregation,
      plasma thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha(6k-PGF1 alpha) as
      indices of observation. The results were: (1) Blood platelet aggregation of Blood
      Stasis patients was higher than that in control (P > 0.001). (2) There were some
      differences of platelet aggregation among different TCM Syndromes. Platelet
      aggregation of Blood Stasis patients with Qi Deficiency was higher than that with
      other Syndromes significantly, and the aggregating rate in those patients was
      higher than that in control (P < 0.05). (3) The platelet aggregation and TXB2 of
      patient with Heart Qi Deficiency were significantly higher than those of the
      control (P < 0.05, P < 0.001), and they were also higher than of other groups of
      blood stasis patient with Spleen, Lung or Kidney Qi Deficiency.

PMID- 8136644
TI  - [Inductive differentiation effect of ginsenosides on human acute non-lymphocytic
      leukemic cells in 58 patients].
AB  - Ginsenosides are the main active component of Panax ginseng. It has been shown
      that ginsenosides have antineoplastic, antiaging, immunologic function enhancing
      and other pharmacological actions. In this article, result of experimental
      studies showed ginsenosides extracted from stem and leaf of Panax ginseng (GSL)
      has inductive differentiation effect on all types of acute nonlymphocytic
      leukemia cells in primary culture. The effect on M5, M4 was most potent, followed
      by M1, M2 and the least, on M3. Through analysis, it was considered that the
      inductive differentiation effect of ginsenosides might be due to the
      comprehensive effect of increasing intracellular cAMP and inducing interferon.
      Since GSL have some other important actions, therefore, if it could be used as a
      differentiation inducer in clinical practice or combined with other
      antineoplastic drugs, it would show co-antineoplastic actions in many aspect.

PMID- 8136645
TI  - [Effects of silybin on red blood cell sorbitol and nerve conduction velocity in
      diabetic patients].
AB  - The effects of silybin on red blood cell (RBC) sorbitol and nerve conduction
      velocity in 14 non-insulin dependent diabetic patients (female 9, male 5; average
      age 58.2 years) were reported. Their RBC sorbitol levels averaged 72.55 +/- 21.61
      nmol/g.Hb, a value almost two times of non-diabetic controls (33.31 +/- 7.82
      nmol/g.Hb). After 4 weeks of silybin (231 mg/d) therapy, RBC sorbitol dropped to
      39.53 +/- 14.94 nmol/g.Hb, a highly significant reduction than that before
      silybin therapy. Silybin treatment had no effect on fasting blood glucose. In
      addition, silybin treatment slightly improved nerve conduction velocity, but
      statistically not significant. This report suggests that silybin may be a potent
      aldose reductase inhibitor, and valuable in the prophylaxis and treatment of
      diabetic complications.

PMID- 8136646
TI  - [Effects of guan-mai-shu on tissue-type plasminogen activator and plasminogen
      activator inhibitor in the plasma of patients with coronary heart disease].
AB  - Effects of Guan-Mai-Shu (GMS), a traditional Chinese medicine preparation, on
      tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor
      (PAI) in the plasma of patients with coronary heart disease were studied. It was
      found that those patients had a significant decrease in t-PA activity (P < 0.05)
      and a significant increase in PAI activity (P < 0.01) compared to healthy
      subjects. After treatment of GMS, t-PA activity significantly increased (P <
      0.001), while PAI activity decreased (P < 0.001). These results indicated that
      GMS could raise t-PA activity and reduce PAI activity in the plasma of patients
      with coronary heart disease.

PMID- 8136647
TI  - [Treatment of upper respiratory infection with mixt. 716 compound].
AB  - Mixt. 716 is composed of traditional Chinese medicinal herbs, including
      Oldenlandia diffusa, Euphorbia humifusa, Onychium japonicum, Acalypha australis.
      150 cases of upper respiratory infection were divided into 716 treatment group
      (89 cases) and control group (61 cases) randomly. The effective rate was 92% in
      treatment group compared with 67% in control group. Experimental studies also
      showed that Mixt. 716 was slightly cytotoxic, it could obviously inhibit
      influenza virus A.

PMID- 8136648
TI  - [Clinical and experimental study on effects of ji shen mixture for infantile
      acute glomerulonephritis].
AB  - 33 cases of acute glomerulonephritis treated with Ji Shen Mixture (JSM) were
      studied with 31 cases treated with Western medical therapy (WM) for comparison
      and 34 healthy subjects as controls. The levels of lipo-peroxide (LPO),
      glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), theromboxane B2
      (TXB2), 6-keto-PGF1 alpha and TXB2/6-keto-PGF1 alpha ratio were examined before
      and after treatment. Compared with healthy controls, the levels of LPO, TXB2,
      TXB2/6-keto-PGF1 alpha of patients increased and that of GSH-Px, 6-keto-PGF1
      alpha decreased significantly, whereas SOD activity had no significant
      difference. After treatment, the level of LPO reduced and GSH-Px activities
      raised significantly, but the effect of JSM group was better than that of WM
      group. It indicated that JSM was more effective in clearing the free radicals.
      The TXB2, TXB2/6-keto-PGF1 alpha dropped and 6-keto-PGF1 alpha elevated
      significantly after treatment, the effects of JSM were markedly better than those
      of WM. Furthermore, JSM was more potent in raising the clearing rate of hematuria
      and proteinuria.

PMID- 8136650
TI  - [Sequential observation on the influence of artificial wind-cold environment to
      immunologic function of mononuclear phagocytic system in mice].
AB  - According to TCM theory of Six Evils, the Wind-Cold is one of the pathogen. In
      order to find the mechanism of Wind-Cold in causing disease, the effect of
      subacute Wind-Cold stimulation on the phagocyte immunization in mice was
      observed. Results showed that through exposing in the Wind-Cold environment, the
      reticuloendothelial system (RES) clearance function and the hydrogen-peroxide
      releasing of peritoneal macrophage were suppressed. Sequential observation showed
      that the peak of immunosuppression occurred on the 3rd day after stimulation and
      began to normalize at 5th day. These results suggested that Wind-Cold stimulation
      could inhibit temporary phagocytosis of macrophage and bacteriocidal effect.
      Action of immunosuppression was believed to be produced by the increase of stress
      hormone after stimulation. Results also suggested that the pathogenic action of
      Wind-Cold on disease is somewhat related with the suppression of nonspecific
      cellular immunity.

PMID- 8136649
TI  - [Changes in some elements, enzymes and energy charge in skeletal muscle of rats
      with spleen qi deficiency].
AB  - In order to investigate the relationship between spleen and muscle, the changes
      of trace elements, enzyme activity, adenine nucleotides and energy charge (EC) in
      the skeletal muscle of rats with Syndrome of Spleen Qi Deficiency (SQD) were
      studied, the curative effects of Sijunzi Tang (SJZT) for SQD were observed too.
      Results showed that in comparing with normal rats, the levels of ATP and EC
      lowered significantly (ATP P < 0.01, EC P < 0.001), the enzyme activity of the
      anaerobic glycolysis increased significantly (P < 0.05), the zinc and iron
      concentrations were higher (P < 0.01) while the copper, potassium and sodium
      concentrations were lower than normal significantly (P < 0.05). These changes
      could be corrected after treatment with SJZT for strengthening spleen and
      tonifying qi. Above-mentioned results suggested that the mechanism of spleen qi
      deficiency is closely related to the abnormal energy metabolism, and the TCM
      theory of spleen dominating muscles might have its scientific basis.

PMID- 8136651
TI  - [Effect of kangdu shengxue yin on production of interleukin-2 of splenic cell in
      irradiated mice].

PMID- 8136652
TI  - [Progress on treatment of coronary heart disease with integrated traditional
      Chinese medicine and Western medicine].

PMID- 8136653
TI  - Transient axonal branching in the developing corpus callosum.
AB  - During development, there is a transient overproduction of axons in the corpus
      callosum; this overproduction of axons is due, in part, to a transient excess of
      neurons that send an axon through the corpus callosum. However, transient axonal
      branching could also contribute to the developmental overproduction of callosal
      axons. To investigate this possibility, we filled developing callosal axons in
      the Syrian hamster with the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate (Dil). Light microscopic analysis showed
      that, indeed, developing callosal axons branch transiently in the hamster:
      branching was robust on postnatal day 0 (P0) and P3 (P0 = the first 24 hr after
      birth), less prominent on P6 and P8, and absent by P11. Immature callosal axons
      branched before or after crossing the midline and at all rostral-caudal and
      medial-lateral levels within the corpus callosum. The majority of callosal axon
      collaterals that were contained within individual 100-micron-thick sections were
      relatively short (mean = 15.1 microns) but some collaterals extended up to
      approximately 135 microns from the main axon trunk before passing out of the
      section in which they were observed. Nearly all of the collaterals emanated from
      the main axon trunk; higher-order collaterals were rare. Some callosal axon
      trunks had multiple collaterals. Branching callosal axons originated from
      multiple cortical areas, including area 17. Electron microscopic observations
      indicated that the processes designated as axon collaterals by light microscopic
      criteria would have been included in electron microscopic counts of developing
      callosal axons. Some callosal axon trunks and branches had ultrastructural
      features that suggested they were degenerating. In cats, developing callosal
      axons branch on embryonic day 57 (E57; the first 24 hr after conception = E0) and
      P0. Thus, it is likely that transient branching of immature callosal axons is a
      generalized feature of mammalian cortical development and that it contributes to
      the overproduction of callosal axons, albeit perhaps to varying degrees, in
      multiple species.

PMID- 8136654
TI  - Using locations to store shape: an indirect effect of a lesion.
AB  - This study had three general points. First, it examined possible visual
      consequences of frontal lesions. A patient with focal damage to the subcortical
      regions of the left frontal lobe, and a small amount of damage near Broca's area,
      was predicted to have impaired brain function in posterior regions that are
      anatomically connected to the damaged site. Second, it showed the utility of
      using positron emission tomography (PET) in conjunction with magnetic resonance
      imaging to characterize "functional lesions." PET revealed reduced metabolism in
      posterior cortical loci that are innervated by fibers from the damaged regions.
      Some of the affected areas are hypothesized to be involved in visual functions,
      specifically the encoding of lines and edges. Third, a series of tests was
      designed to document that the patient had difficulty encoding visual stimuli, and
      then to distinguish among alternative possible causes of this deficit. The
      results suggested that the patient encoded shapes as sets of filled locations if
      possible, which allowed him to use intact processes subserved by brain areas that
      were not affected by the damage. The data were best explained if the lesion
      slowed processing in the ventral system (which encodes object properties),
      allowing the dorsal system (which encodes spatial properties) to produce a
      response more quickly than the ventral system.

PMID- 8136655
TI  - Adolescent pregnancy: the social implications for teens in Saskatchewan.

PMID- 8136656
TI  - Nurse abuse: fighting back legally. What is the legal recourse for a nurse who
      has been abused?

PMID- 8136657
TI  - Nurses and smoking: the quitting approach.

PMID- 8136658
TI  - A Somalian experience.

PMID- 8136659
TI  - An alternative for the NHS.

PMID- 8136660
TI  - Generalists in medicine.

PMID- 8136661
TI  - Community hospitals in the new NHS.

PMID- 8136662
TI  - Rabies in endemic countries.

PMID- 8136663
TI  - Traditional Chinese medicine for eczema.

PMID- 8136664
TI  - European directive on confidential data: a threat to epidemiology.

PMID- 8136665
TI  - Randomised controlled trial of intrapartum fetal heart rate monitoring.
AB  - OBJECTIVE: To compare effectiveness of different methods of monitoring
      intrapartum fetal heart rate. DESIGN: Prospective randomised controlled trial.
      SETTING: Referral maternity hospital, Harare, Zimbabwe. SUBJECTS: 1255 women who
      were 37 weeks or more pregnant with singleton cephalic presentation and normal
      fetal heart rate before entry into study. INTERVENTIONS: Intermittent monitoring
      of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard
      stethoscope by a research midwife, or routine use of Pinard stethoscope by
      attending midwife. MAIN OUTCOME MEASURES: Abnormal fetal heart rate patterns,
      need for operative delivery for fetal distress, neonatal mortality, Apgar scores,
      admission to neonatal unit, neonatal seizures, and hypoxic ischaemic
      encephalopathy. RESULTS: Abnormalities in fetal heart rate were detected in 54%
      (172/318) of the electronic monitoring group, 32% (100/312) of the
      ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9%
      (28/315) of the routine monitoring group. Caesarean sections were performed for
      28% (89%), 24% (76), 10% (32), and 15% (46) of the four groups respectively.
      Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic
      encephalopathy occurred in two, one, seven, and 10 cases in the four groups
      respectively; neonatal seizures occurred only in the last two groups (six and
      nine cases respectively); and deaths occurred in eight, two, five, and nine cases
      respectively. CONCLUSIONS: Abnormalities in fetal heart rate were more reliably
      detected by Doppler ultrasonography than with Pinard stethoscope, and its use
      resulted in good perinatal outcome. The use of relatively cheap ultrasound
      monitors should be further evaluated and promoted in obstetric units caring for
      high risk pregnancies in developing countries with scarce resources.

PMID- 8136666
TI  - Effect of oral gamolenic acid from evening primrose oil on menopausal flushing.
AB  - OBJECTIVE: To evaluate the efficacy of gamolenic acid provided by evening
      primrose oil in treating hot flushes and sweating associated with the menopause.
      DESIGN: Randomised, double blind, placebo controlled study. SETTING: District
      general hospital and teaching hospital. SUBJECTS: 56 menopausal women suffering
      hot flushes at least three times a day. INTERVENTION: Four capsules twice a day
      of 500 mg evening primrose oil with 10 mg natural vitamin E or 500 mg liquid
      paraffin for six months. MAIN OUTCOME MEASURES: Change in the number of hot
      flushes or sweating episodes a month. RESULTS: 56 diaries were analysed, 28 from
      women taking gamolenic acid and 28 from those taking placebo. Only 18 women given
      gamolenic acid and 17 given placebo completed the trial. The mean (SE)
      improvement in the number of flushes in the last available treatment cycle
      compared with the control cycle was 1.9 (0.4) (P < 0.001) for daytime flushes and
      0.7 (0.3) (P < 0.05) for night time flushes in women taking placebo; the
      corresponding values for women taking gamolenic acid were 0.5 (0.4) and 0.5
      (0.3). In women taking gamolenic acid the only significant improvement was a
      reduction in the maximum number of night time flushes (1.4 (0.6); P < 0.05).
      CONCLUSION: Gamolenic acid offers no benefit over placebo in treating menopausal
      flushing.

PMID- 8136667
TI  - Risk of gynaecomastia associated with cimetidine, omeprazole, and other antiulcer
      drugs.
AB  - OBJECTIVE: To study the risk of gynaecomastia associated with cimetidine,
      misoprostol, omeprazole and ranitidine. DESIGN: Open cohort study with nested
      case-control analysis. SETTING: General practices in United Kingdom that had
      computerised offices, 1989-92. SUBJECTS: 81,535 men aged 25-84 years who received
      at least one prescription for cimetidine, misoprostol, omeprazole, or ranitidine
      during the study period. MAIN OUTCOME MEASURES: New occurrences of idiopathic
      gynaecomastia diagnosed by general practitioner. RESULTS: The relative risk of
      gynaecomastia for current users of cimetidine compared with non-users was 7.2
      (95% confidence interval 4.5 to 11.3). Relative risks for misoprostol,
      omeprazole, and ranitidine were 2.0 (0.1 to 10.7), 0.6 (0.1 to 3.3), and 1.5 (0.8
      to 2.6), respectively. Current users of cimetidine on a daily dose > or = 1000 mg
      had more than 40 times the risk of developing gynaecomastia than non-users. The
      period of highest risk was seven to 12 months after starting cimetidine
      treatment. Spironolactone (relative risk 9.3 (3.3 to 26.1)) and verapamil (9.7
      (2.6 to 36.0)) were associated with a relative risk of gynaecomastia comparable
      to one for cimetidine. CONCLUSIONS: Use of cimetidine, but not the three other
      antiulcer drugs, is associated with a substantially greater risk of gynaecomastia
      in men. A strong dose-response relation was present among cimetidine users.

PMID- 8136668
TI  - Use of antidepressants among people committing suicide in Sweden.
AB  - OBJECTIVE: To analyse the outcome of depression in the Swedish population as
      reflected by the detection of antidepressants in a national forensic
      toxicological screening programme of unnatural deaths. DESIGN: Antidepressants
      detected by the National Laboratory of Forensic Chemistry were related to data on
      use expressed in person years of exposure. SUBJECTS: All 7000 cases of unnatural
      death with results from forensic toxicological screening in 1990-1; this included
      3400 (85%) of the 4000 cases of suicide in Sweden. MAIN OUTCOME MEASURES: Number
      of findings of antidepressants in the screening programme and number of findings
      of different antidepressants in relation to their use. RESULTS: Antidepressants
      were found in 585 screening tests, corresponding to 542 subjects or less than 16%
      of the 3400 cases of suicide. Newer, less toxic antidepressants were found more
      often than the older compounds. Toxic concentrations of antidepressants were
      found in only 190 cases (5.6%). CONCLUSION: A consistent finding in surveys of
      suicide is that about half of the patients who commit suicide are depressed. The
      current data suggest that most depressed patients who commit suicide are not
      taking antidepressants immediately before death. Therapeutic failure may be a
      greater problem with antidepressants than toxicity as the results did not
      indicate any advantage of the newer, less toxic antidepressants. All causes of
      death should be included in risk analyses, thereby providing an estimate of
      effectiveness as well as toxicity of antidepressants.

PMID- 8136669
TI  - Provision of consumer health information in general practice.

PMID- 8136670
TI  - Short term effect of withdrawal of diuretic drugs prescribed for ankle oedema.
AB  - OBJECTIVE: To determine the effect of withdrawing diuretic drugs on oedema in
      patients prescribed them for only ankle oedema, excluding patients with cardiac,
      hepatic, or renal failure. DESIGN: Randomised controlled trial. SETTING: 15
      general practices in the Netherlands. PATIENTS: 1202 patients aged 65 years or
      older and taking diuretic drugs, 63 of whom were eligible for the trial. MAIN
      OUTCOME MEASURE: Change in volumetrically determined ankle oedema (oedema index)
      over six weeks. RESULTS: 34 patients were randomised to stop diuretics and 29 to
      the control group. In eight patients diuretics had to be restarted. Among
      patients who had diuretics withdrawn successfully, rebound oedema caused a
      temporary increase in mean oedema index. The peak level (3.5% (95% confidence
      interval 1.5% to 5.2%) was reached in the third week, after which the oedema
      seemed to be returning to the baseline level. CONCLUSION: Few patients who have
      been prescribed diuretics for only ankle oedema clearly have no contraindications
      to withdrawing diuretics. If patients are unlikely to have cardiac insufficiency
      and careful monitoring is provided, withdrawal of diuretics seems to be feasible,
      though moderate rebound oedema may occur for a short time.

PMID- 8136671
TI  - New roles for general practitioners.
AB  - General practice is likely to change greatly over the next few years. Increases
      in care in the community and day surgery will lead to more work, and the demand
      for better data on practice activity will mean the development of audit and
      epidemiological work. To make time general practitioners will have to learn to
      delegate work that does not require a doctor. Fundholding has already stimulated
      some practices to bring services to patients rather than send patients to
      hospital, and this trend seems set to continue. It is important to pool
      resources, not only within practices but among other practices in the area--joint
      action will increase the ability to improve the services for patients. If general
      practitioners take the opportunity to gain control of the changes the morale of
      the profession should improve.

PMID- 8136672
TI  - Late presentation of Kartagener's syndrome. Consequences of ciliary dysfunction.

PMID- 8136673
TI  - The ethics of data utilisation: a comparison between epidemiology and journalism.
AB  - Legal controls over data collection in European countries have badly affected the
      work of epidemiologists. By contrast, journalists have been allowed far greater
      freedoms. The aims and tasks of both professions are in line with accepted values
      in our society--especially those of inquiry and the benefits of an open society.
      Society seems willing to accept that, in the interests of wider public good,
      journalism may sometimes invade individuals' privacy and do them harm, but it is
      not prepared to offer epidemiology an equal measure of tolerance.

PMID- 8136674
TI  - ABC of emergency radiology. The hip.

PMID- 8136675
TI  - Capture-recapture techniques. Difficult to use in developing countries.

PMID- 8136676
TI  - Capture-recapture techniques. More unreliable in humans than in birds.

PMID- 8136677
TI  - Birth weight and blood pressure. No evidence for a U shaped relation.

PMID- 8136678
TI  - Intrauterine growth and serum cholesterol. Link may be spurious.

PMID- 8136679
TI  - Long term use of sumatriptan.

PMID- 8136680
TI  - Minimally invasive surgery. Laparoscopic nephrectomy unproved in controlled
      clinical trials.

PMID- 8136681
TI  - Renal failure after topical use of NSAIDs.

PMID- 8136682
TI  - Genetic susceptibility to non-insulin dependent diabetes.

PMID- 8136683
TI  - Safety of tamoxifen.

PMID- 8136684
TI  - Breast feeding and diabetes mellitus.

PMID- 8136685
TI  - Clusters of anophthalmia.

PMID- 8136686
TI  - Genetic prediction of adult onset disease.

PMID- 8136687
TI  - Tuberculous pericarditis.

PMID- 8136688
TI  - Imaging methods used in acute aortic dissection.

PMID- 8136689
TI  - Medical ethics and human reproduction. Scientists predict unbalanced future with
      sex selection.

PMID- 8136690
TI  - Radiological assessment of the knee in children.

PMID- 8136691
TI  - Bed sharing and sudden infant death syndrome.

PMID- 8136692
TI  - GP facilitators and HIV infection. Heterosexual infection less common than other
      routes.

PMID- 8136693
TI  - GP facilitators and HIV infection. Shared care better for GPs and specialists.

PMID- 8136695
TI  - Allergy testing in supermarkets. Misleads susceptible people.

PMID- 8136694
TI  - Prostitution: would legislation help?

PMID- 8136696
TI  - GP facilitators and HIV infection. Other health professionals can be
      facilitators.

PMID- 8136697
TI  - In vitro biosynthesis of peptolide SDZ 90-215 by a 1.2 MDa multienzyme
      polypeptide.
AB  - An enzyme fraction with catalytic activities for the biosynthesis of the
      pipecolic acid containing cyclopeptolide SDZ 90-215 was partially purified and
      characterized from the genus Septoria. The crude cell homogenate was subjected to
      polyethyleneimine precipitation, ammonium sulfate precipitation and FPLC gel
      filtration. The denatured enzyme shows an apparent molecular mass of 1.2 MDa in
      3% SDS-PAGE. Peptolide SDZ 90-215 synthetase catalyzes the ATP-PPi exchange
      reaction dependent on all substituent amino and hydroxy acids. SDZ 90-215
      synthetase synthesizes the peptolide in vitro when incubated together with D
      lactic acid, all constitutive amino acids in their N-unmethylated form, ATP,
      magnesium chloride and S-adenosyl-L-methionine. The yield of SDZ 90-215 is higher
      when O-methyl-L-tyrosine instead of L-tyrosine is used, indicating that O
      methylation of tyrosine is not carried out by the synthetase.

PMID- 8136698
TI  - Changes in protein stability upon chemical modification of lysine residues of
      bovine serum albumin by different reagents.
AB  - Using acetic anhydride, potassium cyanate and O-methyl isourea six chemically
      modified derivatives of bovine serum albumin with chemical modification on lysine
      side chains have been prepared. All the modified preparations were found to be
      homogeneous with respect to size and charge. Size exclusion chromatography on a
      calibrated Sephacryl S-300 column revealed that whereas acetylation and
      carbamylation produce significant increase in Stokes' radius, guanidination
      produces a slight decrease in Stokes' radius. Stability of native and different
      modified preparations was studied by following urea induced denaturation using
      the technique of uv difference spectroscopy and by measuring delta GDH2O and
      delta delta GD(urea)50% from these data. The order of stability of different
      preparations was found to be guanidinated > native > carbamylated > acetylated.

PMID- 8136699
TI  - Functional expression of rat alpha 1 Na,K-ATPase containing substitutions for
      cysteines 454, 458, 459, 513 and 551.
AB  - Site-specific mutagenesis was used to prepare the following substitutions of the
      rat alpha 1 Na,K-ATPase: Cys 513-->Ala, Cys 454+458+459-->Ala and Cys 551-->Ser.
      Ouabain-resistant HeLa cell cells expressing rat alpha 1 wild type and each of
      the mutants were selected, indicating that the Cys-substituted enzymes are
      active. Membranes isolated from HeLa cells expressing wild-type and mutant cDNAs
      all exhibit ouabain-insensitive Na,K-ATPase activity. The apparent K0.5 for ATP
      of the wild-type, Cys454+458+459-->Ala, and Cys551-->Ser enzymes are similar,
      while that of the Cys513-->Ala enzyme is 2.6-fold higher. These results suggest
      that either Cys454--Cys458 and Cys513--Cys551 are not involved in disulfide
      bonds, as recently suggested by Gevondyan et al (Biochem. Mol. Biol. Int. 29, 327
      337, 1993), or that these two disulfides in the ATP binding region of the alpha
      subunit are not required for Na,K-ATPase function.

PMID- 8136700
TI  - Characterization of the Mg(2+)-ATPase activity of the human erythrocyte membrane.
AB  - The Mg(2+)-dependent ATPase activity of human erythrocyte ghosts undergoes
      biphasic activation in the presence of ATP (K0.5 approximately 20 microM and 400
      microM). Inhibition by vanadate is also biphasic with the most sensitive
      component (IC50 approximately 100 microM) responsible for the remaining activity.
      La3+ inhibits approximately 70% of activity (IC50 approximately 25 microM) while
      Cd2+ can fully inhibit activity (IC50 approximately 60 microM). Partially
      purified activity was obtained by extracting ghosts with Triton X-100, followed
      by chromatography over Sepharose CL-2B. Triton distorts the curves for inhibition
      by vanadate and the activation by ATP. The partially purified activity is
      inhibited by Ca2+ (IC50 approximately 0.4 mM). These results, together with data
      from other studies, suggest that the total Mg(2+)-ATPase activity in the membrane
      represents at least two separate enzymes. Only the activity which is highly
      sensitive to vanadate appears to be involved in erythrocyte shape change.

PMID- 8136701
TI  - Binding of collagen causes intracellular mobilization of calcium in human
      mononuclear cells.
AB  - The possibility that extracellular matrix-cell surface interaction might lead to
      signalling was examined in human mononuclear cells. In mononuclear cells loaded
      with Indo-1 acetoxymethylester, collagen binding elicited a 2-3 fold increase in
      cytosolic free calcium concentration within seconds. Plasma fibronectin, serum
      albumin and heparin did not cause any significant change in intracellular calcium
      levels. Collagen I, collagen IV and glucosylated collagen I evoked an increase in
      intracellular Ca++ both in the presence and absence of extracellular calcium.
      However, in the presence of 2mM EDTA, the increase in cytosolic free calcium
      concentration caused by collagen I and collagen IV was partly abolished,
      suggesting the requirement of a cation-dependent interaction of collagen with
      mononuclear cells. Glucosylated collagen induced intracellular calcium
      mobilization even in the presence of EDTA suggesting a cation-independent
      interaction. These results indicate that collagen binding induces rapid
      mobilization of calcium in human mononuclear cells, apparently from intracellular
      sources.

PMID- 8136702
TI  - Purification and characterization of human macrophage migration inhibitory
      factor: evidence for specific binding to glutathione and formation of subunit
      structure.
AB  - We cloned cDNA of human macrophage migration inhibitory factor (MIF) from a T
      cell line encoding 116 amino acid residues and expressed it in E. coli. MIF
      specifically bound glutathione (dissociation constant = 600 microM), and the
      protein was effectively purified by an S-hexylglutathione Sepharose affinity
      column. MIF was homogeneous on SDS-PAGE and the molecular weight was calculated
      as 12.5 kDa. The molecular weight was in excellent agreement with that of the
      primary structure assumed from the cDNA. On the other hand, the molecular weight
      in the native form calculated by Sephadex G-100 gel chromatography was 24.3 kDa,
      which suggested that MIF formed a dimeric structure. To further confirm the
      native molecular weight, we carried out analytical ultracentrifugation. This
      precise hydrodynamic analysis revealed that the native molecular weight was 24.8
      kDa, which confirmed that MIF existed as a homodimeric form.

PMID- 8136703
TI  - Distribution and some properties of sheep (Ovis aries) angiotension converting
      enzyme.
AB  - Angiotensin converting enzyme (ACE) was measured in 15 sheep tissues by
      spectrophotometric assay with hippuryl-L-histidyl-L-leucine as substrate.
      Captopril inhibited the ACE activities of all the tissues. The ACE activity was
      highest in caput epididymidis, corpus epididymidis, cauda epididymidis, kidney
      and testis. The ACE activity was moderate in retina, little in cornea and lowest
      in lens. The greater increase in epididymal ACE activity than that of testicular
      ACE activity on maturation indicates that epididymal ACE may be highly sensitive
      to hormones. Chloride functioned as non-essential activator of corneal and
      retinal ACE. The ACE activities of sheep tissues are compared with those found in
      other species and probable role of ACE in different tissues is discussed.

PMID- 8136704
TI  - Effects of metalloprotease inhibitors on the conversion of proendothelin-1 to
      endothelin-1.
AB  - The IC50 values of phosphoramidon, CGS 25015, CGS 26129, thiorphan and
      benazeprilat for inhibition of endothelin converting enzyme partially purified
      from porcine aortic endothelial cells were 3.5, 18, 58, > 100 and > 100 microM,
      respectively. A similar rank order of potency was observed for inhibition of the
      proendothelin-1 (proET-1) -induced pressor response in the rat where
      phosphoramidon, CGS 25015, CGS 26129, thiorphan and benazeprilat at 30 mg/kg i.v.
      produced 65, 57, 27, 12, and 0% inhibition, respectively. A slightly different
      rank order of potency was obtained in the proET-induced contraction of porcine
      coronary arteries where IC50 values of < 10, 10-30, 10-30, 30-100 and 30-100
      microM were exhibited by CGS 25015, CGS 26129, phosphoramidon, thiorphan and
      benazeprilat, respectively. These data indicate that the endothelin converting
      enzymes in the three systems studied are similar, except that phosphoramidon is a
      slightly more potent inhibitor in the in vitro assay and the in vivo pressor test
      than in the smooth muscle contraction assay.

PMID- 8136705
TI  - Topical application and uptake of vitamin E acetate by the skin and conversion to
      free vitamin E.
AB  - Radioactive tocopherol acetate was diluted with either (1) unlabelled tocopherol
      acetate or (2) Delios S (Henkel, a medium chain triglyceride prepared from
      fractionated coconut oil), a cosmetic base. These preparations were applied
      topically to a 2 cm diameter circle of skin. After 24 hours the percent of label
      which was still removable by swabbing the skin surface was 1.7% for (1) and 11.5%
      for (2). The central circles contained 2.86% of the label applied in 259 mg skin
      for (1) and 24.2% of the label applied in 226 mg skin for Delios S for (2).
      Surprisingly, combined samples of approximately one third of the side skin
      contained 0.7% of the label applied in 460 mg for (1) and 13.2% of the applied
      label in one third of the side skin in 523 mg for (2). The percent conversion to
      tocopherol in the skin central areas was 4.52% by HPLC and 4.13% by TLC for (1)
      and 5.97% for (2). In the side skin the percent conversion to tocopherol was 5.0%
      for (1) and 6.01% for (2).

PMID- 8136706
TI  - Effect of naloxone in the median eminence on gonadotrophin secretion in intact
      male rats.
AB  - To evaluate whether the median eminence (ME) is a site of action of opioids on
      gonadotropin secretion, we injected naloxone into the ME in male rats and
      measured LH and FSH serum levels. Injection into the ME of either 0.5 or 1
      microgram of naloxone significantly decreased serum LH levels 10 and 30 min
      postinjection. A dose of 0.1 microgram had not effect. Naloxone at the doses used
      had no significant effect on FSH secretion. From these data it can be concluded
      that endogenous opioids exert a tonic stimulation on LH secretion under our
      experimental conditions.

PMID- 8136707
TI  - Oligonucleotides complementary to the alpha-sarcin domain of 28S rRNA inhibit
      cell-free protein synthesis.
AB  - Oligodeoxynucleotides complementary to the alpha-sarcin domain of rat 28S rRNA
      inhibit cell-free protein synthesis. The poly(U) translation system containing
      Artemia salina ribosomes was more sensitive to inhibition than the system
      containing rat liver ribosomes. The 21-mer, which was the most effective of the 7
      oligonucleotides tested, hybridized with naked 28S rRNA. Hybridization with whole
      ribosomes, assayed by S1 nuclease protection, occurred only at high ionic
      strength or with ribosomes actively engaged in protein synthesis.

PMID- 8136708
TI  - Modulation of DNA synthesis by microtubule-associated protein 2 in the nuclear
      matrix isolated from Physarum polycephalum.
AB  - The mechanism of stimulation of DNA synthesis by microtubule-associated protein 2
      (MAP2) was examined in the nuclear matrix isolated from Physarum polycephalum.
      Porcine brain MAP2 stimulated DNA synthesis by the matrix with exogenous
      templates, but not with endogenous templates. Kinetic analyses showed that MAP2
      decreases the Km of the matrix for deoxyribonucleoside triphosphates. Comparison
      of the Km values of active- and latent-type DNA replication machineries of
      Physarum suggested a possible role for MAPs or MAP-like proteins in DNA
      replication.

PMID- 8136709
TI  - Purification and characterization of the branched chain alpha-ketoacid
      dehydrogenase complex from Saccharomyces cerevisiae.
AB  - Branched chain alpha-ketoacid dehydrogenase complex was purified from
      Saccharomyces cerevisiae by polyethylene glycol fractionation and chromatography
      on Sephacryl S-200, DEAE-cellulose and Sepharose CL-2B. Electrophoresis on sodium
      dodecyl sulfate-polyacrylamide gels indicated the enzyme contained subunits of
      M(r) = 57,000, 52,000, 47,000 and 38,000. The specific activity of the purified
      enzyme was 0.82 mumol NADH/min/mg protein at 30 degrees C with 16 mM alpha
      ketoisovalerate as substrate. The apparent Km values for alpha-ketoisovalerate,
      alpha-ketoisocaproate and alpha-keto-beta-methylvalerate were 21, 22, and 20 mM,
      respectively. The preparation was also able to oxidize the intermediates of
      threonine and methionine metabolism, alpha-keto-gamma-methiolbutyrate and alpha
      ketobutyrate, with Km values of 13 and 8 mM, respectively.

PMID- 8136710
TI  - Modifications in the low mobility group nuclear proteins by reactive metabolites
      of diethylstilbestrol.
AB  - In this study we have investigated the potential of nuclear activation system to
      convert diethylstilbestrol (DES) to reactive metabolites, which bind to low
      mobility nonhistone nuclear proteins. Reaction of DES with nuclei in the presence
      of cumene hydroperoxide or NADPH revealed binding of DES in low mobility group
      (LMG) nonhistone nuclear proteins analyzed by both organic solvent extraction and
      gel electrophoresis methods. Gel electrophoresis experiments revealed that five
      LMG proteins of MW 130, 108, 72, 51, and 45 KDa were irreversibly bound to 3H
      DES. The kinetic constants, Km and Vmax, of this binding reaction in the presence
      of cumene hydroperoxide were 39 uM and 1225 pmol/mg protein/30 min, respectively.
      This binding was significantly inhibited by cytochromes P450 inhibitors. Low
      molecular weight thiols, i.e., glutathione and cysteine, or thiol modifiers such
      as n-ethylmaleimide, dithionitrobenzoic acid, and hydroxymercuric benzoate,
      drastically inhibited binding. The binding of DES metabolites to both
      transcriptionally active and inactive chromatins LMG proteins was observed. In
      summary, DES is metabolized to transcriptionally active chromatin LMG protein
      binding metabolites presumably by nuclear cytochromes P450. These data suggest
      that an analogous in vivo modification in the transcriptionally active chromatin
      LMG nonhistone proteins by DES metabolites may influence gene transcription.

PMID- 8136711
TI  - The anti-proliferative effects of nicotinamide and 3-aminobenzamide on human
      smooth muscle cells in vitro.
AB  - The proliferation of cultured human arterial smooth muscle cells (HASMC) was
      suppressed by nicotinamide and its analogue, 3-aminobenzamide, in a concentration
      dependent manner, based on cell count and [3H]thymidine incorporation into DNA.
      The addition of 10 and 15 mM nicotinamide, or 6 mM 3-aminobenzamide, to HASMC,
      for 96 h, resulted in a 19.3%, 44% and 41.5% reduction of cell growth and
      inhibition of DNA synthesis. Since c-myc protooncogene expression has previously
      been correlated with cell proliferation, the steady state level of its mRNA was
      determined in control and treated HSMC by Northern analysis, following a 1 h
      treatment with the respective chemicals. Whereas c-myc mRNA was suppressed by
      nicotinamide in proportion to its ability to reduce HASMC growth, down regulation
      of c-myc by 3-aminobenzamide was much less than the observed antiproliferative
      effect. These results suggest that the growth regulatory properties of
      nicotinamide and 3-aminobenzamide in HASMC are probably unrelated to their
      activity in controlling c-myc gene expression.

PMID- 8136712
TI  - Partial purification and characterization of soluble acid invertases from rice
      (Oryza sativa) leaves.
AB  - There are three soluble acid invertases in the leaves of rice. They could be
      separated by DEAE1-Sephacel chromatography, and named IT1, IT2 and IT3. The
      molecular weights of IT1, IT2 and IT3, determined by HPLC gel filtration
      chromatography, were 220 kD, 59 kD and 67 kD, respectively. Their pI values were
      6.2, 5.2 and 4.9, respectively. The pH optima of IT1, IT2 and IT3 were 3.5, 6.0
      and 5.5 respectively. All of them could hydrolyze sucrose and raffinose but not
      maltose, therefore they are all beta-fructofuranosidases. The apparent Km values
      for sucrose and raffinose of IT3 were 7.0 and 14.5 mM, respectively. Exogenous
      protein BSA could activate IT3. IT3 was inhibited by metal ions--Pb2+, Zn2+,
      Cu2+, Hg2+ and Ag+. The sulfhydryl group inhibitor, PCMB, and serine protease
      inhibitor, PMSF, had no effects on IT3 activity. It might indicate that cysteine
      and serine did not participate directly the active site catalytic reaction of
      IT3.

PMID- 8136713
TI  - Effect of ionophore A23187 and thapsigargin on serine incorporation into
      phosphatidylserine in intact and permeabilized glioma C6 cells at high and low
      Ca2+ concentrations.
AB  - Intact and permeabilized glioma C6 cells were incubated with [14C]serine in media
      containing low (100 nM) or high (2 mM) [Ca2+] and serine incorporation into
      phosphatidylserine was examined. In all cases thapsigargin, a blocker of the
      endoplasmic reticulum Ca(2+)-ATPase, diminished this process, whereas the action
      of the ionophore A23187 was dependent on the external calcium concentration and
      time of incubation. In permeabilized cells incubated at 100 nM Ca2+, serine
      incorporation into phosphatidylserine was diminished when the endoplasmic
      reticulum Ca2+ levels were lowered by the ionophore. In intact cells incubated at
      2 mM CaCl2, addition of A23187 had no effect for the first 30 min and later
      decreased [14C]serine incorporation. This result seems to be not connected with
      the degradation of already formed phosphatidylserine, or with an enhanced
      metabolic conversion of this phospholipid, but with the decrease of its
      synthesis. The mechanism of this last process appears to be involved in the
      ionophore-induced perturbation of cellular Ca2+ homeostasis. Our results indicate
      that phosphatidylserine synthesis is a Ca(2+)-regulated process.

PMID- 8136714
TI  - Identification of AT2 angiotensin receptors on Swiss 3T3 cells.
AB  - Swiss 3T3 cells express high-affinity receptors for angiotensin II (KD = 0.8 nM,
      110,000 receptors/cell). Binding of the peptide to these receptors did not
      activate phosphatidylinositol 4,5 bisphosphate hydrolysis, and did not increase
      intracellular [Ca2+] or activate protein kinase C. The relative binding
      affinities of highly-selective antagonists characterised these receptors as the
      AT2 subtype. However, in contrast to the signalling events reported in some other
      cells that express AT2 receptors, AII had no apparent effect on either cyclic GMP
      levels or phosphotyrosine phosphatase activity in Swiss 3T3 cells. Furthermore,
      angiotensin II (either alone or in combination with growth factors) was not
      mitogenic to Swiss 3T3 cells.

PMID- 8136715
TI  - Fractionation and identification of cytoplasmic tRNAS and structural
      characterization of a phenylalanine and a leucine tRNA from cucumber hypocotyls.
AB  - Total cytoplasmic tRNAs from cucumber hypocotyls were fractionated by two
      dimensional polyacrylamide gel electrophoresis into about 56 species. Of these,
      32 tRNA species were identified by aminoacylation as tRNA specific for 15 amino
      acids. Furthermore, cytoplasmic tRNA(Phe) and tRNA(Leu(NAA)) were purified to
      homogeneity by the combination of RPC-5 column chromatography and two-dimensional
      polyacrylamide gel electrophoresis. The primary structure of tRNA(Leu(NAA)) and
      the modified nucleotides of tRNA(Phe) have been determined. The sequence of
      cucumber cytoplasmic tRNA(Leu(NAA)) is identical to that of bean cytoplasmic
      tRNA(Leu(NAA)) except for three base differences in the variable loop.

PMID- 8136716
TI  - Modern advances in microscopy: from animal to atom.
AB  - The ultimate goal of the modern physiologist is to understand and integrate the
      biochemistry, biophysics and physiology of undisturbed living cells. To
      accomplish this goal requires the development and application of approaches that
      can non-invasively probe a variety of dynamic cellular processes. Although no
      technique is truly non-invasive, recently developed methods are approaching this
      objective. Fluorescence has become the most popular optical tool for measuring
      the ion properties inside living cells, due to sensitivity, specificity, and
      spatial and temporal resolution. All of these systems use the same basic
      principle, i.e., the cell or tissue is exposed to a concentrated specific beam of
      excitation light and the resultant fluorescent signal is detected on a collection
      device. Photomultiplier tube systems will give maximal temporal resolution.
      Intensified video camera systems allow for maximal spatial resolution, and
      simultaneous measurement of fields of cells. Improved spatial resolution can be
      obtained using confocal microscopes providing both 2D and 3D molecular
      distribution and activity maps from within cells. In addition to obtaining
      spatial information from within cells, it is now possible to measure dynamic
      surface morphometric changes with Angstrom level resolution using the technique
      of Atomic Force Microscopy (AFM). This review will summarize the different uses
      of both conventional and nonconventional microscopy to examine dynamic changes in
      living cells.

PMID- 8136717
TI  - Interactions of the pineal hormone melatonin with oxygen-centered free radicals:
      a brief review.
AB  - Melatonin,N-acetyl-5-methoxytryptamine, is a hormonal product of the pineal
      gland. Its synthesis is higher at night than during the day in all vertebrates
      including man. Once melatonin is produced in the pineal gland it is quickly
      released into the vascular system. The rapid release of melatonin is generally
      believed to relate to its high lipophilicity which allows it to readily pass
      through the membrane of the pinealocytes and the endothelial cells which line the
      capillaries. The result of the nocturnal synthesis and secretion of melatonin is
      high blood levels at night. Also because of its highly lipophilic nature,
      melatonin from the blood readily escapes into every other bodily fluid and all
      cells in the body. Until recently it was generally thought that melatonin's
      action in the organism depended on its exclusive interaction with specific
      receptors on cells located in discrete locations. Certainly, the interactions of
      melatonin with these membrane-bound receptors are believed to mediate the
      endocrine and circadian rhythm effects of melatonin. It was recently discovered,
      however, that melatonin's primary action may not depend on the previously
      described membrane receptors. We have found that melatonin is a very potent
      hydroxyl radical scavenger; free radicals and the hydroxyl radical in particular,
      because of its very high reactivity, can be extremely damaging to macromolecules
      in cells. Compared to glutathione and mannitol, two well known free radical
      scavengers, melatonin is a more powerful scavenger and affords protection of
      molecules, especially DNA, from oxidative damage. Melatonin's extremely high
      diffusibility is important for its scavenging action because this feature allows
      it to enter all cells and every subcellular compartment. Whereas the free radical
      quenching activity of melatonin does not require a receptor, we also have
      evidence that it may be bound in the nucleus thereby providing on-site protection
      to DNA. Besides scavenging the highly toxic hydroxyl radical, melatonin also
      stimulates glutathione peroxidase activity which metabolizes the precursor of the
      hydroxyl radical, hydrogen peroxide, to water. Thus, melatonin has at least two
      means to protect the cell from oxidative damage, i.e., it breaks down hydrogen
      peroxide to harmless water and, in the event any hydroxyl radicals are formed,
      melatonin scavenges them. Melatonin may be the premier molecule to protect the
      organism from oxidative damage.

PMID- 8136718
TI  - Human neuroblastoma cells express a novel metallo-endopeptidase activity able to
      inactivate atrial natriuretic factor: inhibition during retinoic acid-induced
      differentiation.
AB  - A new metallo-endopeptidase which hydrolyzes atrium natriuretic factor (ANF) has
      been isolated from human neuroblastoma NB-OK-1 cells. In the present study we
      show that this metallo-endopeptidase is also present in several other human
      neuroblastoma cell lines, which include CHP 100, SH-SY5Y, SK-N-BE(2), BE(2)-C and
      BE(2)M-17. Additionally, we show that this endopeptidase activity is reduced to
      about 20% of the control during retinoic acid (RA)-induced neuronal
      differentiation in the RA-sensitive SK-N-BE(2) cells, but not in the RA-resistant
      BE(2)-M17 cells. This suggests that the inhibition is related to neuronal
      differentiation and not to a direct effect of 5 microM RA on the enzyme activity.
      This new enzyme is clearly distinct from neutral endopeptidase (NEP, EC
      3.4.24.11) and angiotensin-converting enzyme (ACE,EC 3.4.15.1), since specific
      inhibitors for these endopeptidases (10 microM phosphoramidon and 1 mM captopril,
      respectively) had no effect on their activity. However, this enzyme was inhibited
      100% by 10 mM o-phenanthroline showing an inhibitory spectrum similar to that of
      another novel metallo-endopeptidase recently isolated in our laboratory from
      Xenopus laevis skin secretion. Although the physiological function of this new
      enzyme in human neuroblastoma cells is not known at the present time, we suggest
      that it may participate in inactivation of neuropeptides such as atrium
      natriuretic factor (ANF), substance P, somatostatin-14 and bradykinin in vivo.

PMID- 8136719
TI  - Blood glucose and insulin response to intravenous glucose by patients with
      chronic Chagas' disease and alcoholism.
AB  - Blood glucose and insulin responses to intravenous glucose 500 mg/kg in a group
      of alcoholic chagasic patients (Group I, N = 15) were assessed and compared to
      those of a group of patients with Chagas' disease without alcoholism (Group II, N
      = 16), a group of alcoholics without Chagas' disease (Group III, N = 22), and a
      group of non-alcoholics without Chagas' disease (Group IV, N = 15).
      Determinations of serum glucose and insulin were done under fasting conditions, 5
      and 10 min after the injection of 50% glucose. There was no difference in mean
      serum glucose levels between groups. Mean serum insulin levels at times 5 and 10
      min and for the total integrated response were lower (P < 0.05) in Groups I and
      II as compared to Group IV; at time 10 min the mean was lower (P < 0.05) in Group
      III as compared to Group IV. There was a nonsignificant trend for a lower
      insulinemic response in Group I as compared to Group II. These data suggest
      denervation of or injury to pancreatic B cell by Chagas' disease.

PMID- 8136720
TI  - Reversal of learned helplessness by chronic lithium treatment at a prophylactic
      level.
AB  - 1. The effect of chronic lithium (Li) administration in a learned helplessness
      (LH) model was investigated. Female Wistar rats (190-210 g) received either tap
      water ad libitum (N = 56) or 20 mM LiCl (N = 63) in the drinking water or were
      water restricted (35% based on lower liquid intake of rats receiving lithium, N =
      40) for 30 days. On the 28th day, each of these groups was divided into three
      subgroups which received escapable (ES), inescapable (IS) or no shock (NS)
      treatment in shuttle boxes. All groups were submitted to the escape test on the
      29th day and sacrificed on the 30th day, when blood samples were taken for
      measurement of serum lithium, sodium and potassium concentrations. 2. The NS
      group had lower serum Li levels (0.36 +/- 0.06, N = 15) than the ES (0.46 +/-
      0.07, N = 15) or IS group (0.44 +/- 0.09, N = 25). The Li-pretreated group
      subjected to IS had a more effective escape performance than the IS group under
      water restriction and showed the same behaviour as animals not submitted to
      shocks. 3. We conclude that chronic treatment with Li at a serum level of 0.44 +/
      0.09 mEq/l prevents learned helplessness in rats. These results corroborate the
      validity of the use of this model for the assessment of the capacity of Li to
      protect against some depressive episodes.

PMID- 8136721
TI  - Paw preference in mice with callosal defects induced by prenatal gamma
      irradiation.
AB  - The development of the corpus callosum of male Swiss mice was perturbed by
      exposure to gamma radiation at embryonic day 16 with total doses of 2 Gy (N = 48)
      or 3 Gy (N = 26). At adulthood paw preference was studied in these callosal
      defective animals and in 93 control nonirradiated male Swiss mice. The analysis
      of directional laterality indicated a populational tendency for right paw use in
      the 2 Gy group (60%) that was markedly increased in the 3 Gy group (95%). In the
      3 Gy group, directional laterality was significantly different from chance in
      contrast to that observed in normal controls (49%). In the three groups most mice
      presented a significant individual paw preference. These data are consistent with
      our hypothesis that the early absence of the corpus callosum disrupts the normal
      pattern of directional asymmetries.

PMID- 8136722
TI  - Differential effect of amphotericin B on the three evolutive stages of
      Trypanosoma cruzi and on the host cell-parasite interaction.
AB  - 1. Amphotericin B (Am.B) was shown to have a direct effect on T. cruzi, with the
      three forms of the parasite presenting different susceptibilities to the drug in
      the following order: amastigotes > trypomastigotes > epimastigotes. These
      differences highlight the importance of using the vertebrate forms of the
      parasite in tests of new drugs. 2. The treated parasites showed alterations of
      the plasma membrane, suggesting that, as in fungi, the primary effect of Am.B was
      probably via formation of complexes with membrane components. 3. When exposed to
      filipin, another polyene antibiotic, the three parasite forms were observed to
      present a similar order of susceptibility, with comparable ultrastructural
      modifications. 4. Higher concentrations of Am.B were required to damage the
      intracellular parasites in vitro, 2.3 micrograms/ml for parasites inside
      peritoneal macrophages and 7 micrograms/ml for parasites inside heart muscle
      cells. 5. Am.B is effective against the parasite, but is also toxic to mammalian
      cells. Testing of Am.B for the control of Chagas' disease by blood transfusion
      may be useful, since bloodstream forms are lysed by lower concentrations of the
      drug than those required to affect intracellular parasites.

PMID- 8136723
TI  - Intracerebroventricular administration of canatoxin to rats increases the
      circulating levels of luteinizing hormone.
AB  - Recent evidence has implicated the central nervous system as a target organ for
      canatoxin, a toxic protein present in Canavalia ensiformis seeds. This toxin
      activates the lipoxygenase pathway of arachidonic acid metabolism and can thus
      induce the release of substances mediated by lipoxygenase products. In the
      present study, the circulating levels of luteinizing hormone (LH) were measured
      by RIA in male Wistar rats (200-240 g) after the administration of canatoxin into
      the lateral cerebral ventricle. Canatoxin (0.5-2 micrograms in 2 microliters
      daily for 3 days) caused a dose- and time-dependent increase in the plasma levels
      of LH. The total dose of canatoxin used is subconvulsive. At 2, 4 and 24 h after
      2 micrograms of canatoxin LH levels were increased by 10%, 43% and 61%,
      respectively, compared to vehicle-injected animals (0.18 +/- 0.03 ng/ml). This
      response to 2 micrograms of canatoxin was not attenuated by pretreatment with two
      different lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA, 125 mg/kg) or
      esculetin (ECLT, 125 mg/kg), ip, 1 h before each canatoxin (CNTX) injection; %
      increase in LH with CNTX alone: 61%; CNTX+NDGA: 54%; CNTX+ECLT:76%; N = 5/group.
      These data show that intracerebral injection of CNTX in rats increases
      circulating levels of LH via a mechanism that is independent of the lipoxygenase
      pathway.

PMID- 8136724
TI  - Water replacement and thermoregulatory responses during prolonged exercise.
AB  - The present study was designed to compare the thermoregulatory responses of 12
      young adult males who were required to exercise wearing heavy clothing under
      three different conditions: 1) without water replacement (WW), 2) with water
      replacement (600 ml prior to exercise and 240 ml at the 15th, 30th and 45th
      minute of exercise) (W15), and 3) with water replacement (600 ml prior to
      exercise, 36 ml during the first minute of exercise and 36 ml at 3-min intervals
      throughout exercise) (W3). The mean heart rate (HR) (147 +/- 14.6 beats/min),
      mean rectal temperature (Mtre) (37.39 +/- 0.24 degrees C) and mean body
      temperature (MBT) (36.73 +/- 0.24 degrees C) under WW conditions were
      significantly higher than the values observed under W15 conditions (137 +/- 6.18
      beats/min, 37.18 +/- 0.17 degrees C and 36.57 +/- 0.18 degrees C, respectively)
      and W3 conditions (138 +/- 10.1 beats/min, 37.18 +/- 0.21 degrees C and 36.51 +/-
      0.24 degrees C, respectively). The temperature differences could be partially
      attributed to a direct effect of the cold water ingested. No significant
      differences were detected between conditions W15 and W3 for any of the variables
      studied.

PMID- 8136725
TI  - Effect of ethanol on cortical spreading depression.
AB  - The effects of intragastric ethanol (3 g kg-1 day-1 in a total volume of 3.8
      ml/kg, for 7 days) on cortical spreading depression (SD) were studied in adult
      Wistar rats (N = 10). Control animals (N = 8) received an equivalent volume of
      distilled water for the same period of time. SD was elicited by stimulation of
      one point of the right frontal cortex with 2% KCl for 1 min at 20-min intervals
      and was recorded for 6 h at two points on the parietal surface of the same
      hemisphere. The ethanol group failed to gain weight during treatment, while the
      mean weight of the control group increased by 17 g. Rats treated with ethanol
      displayed higher mean SD velocities (range: 3.87 +/- 0.54 to 4.58 +/- 0.76
      mm/min) than the control animals (range: 2.99 +/- 0.30 to 3.78 +/- 0.46 mm/min),
      the difference being significant until the fourth h of recording. The results
      indicate that ethanol intake for 7 days increases the susceptibility of the
      cerebral cortex to SD in adult rats.

PMID- 8136726
TI  - Presence of colonization factor antigen IV (CS5CS6) in O29:H21 enterotoxigenic
      Escherichia coli isolated from children with diarrhea in Brazil.
AB  - 1. Enterotoxigenic Escherichia coli (ETEC) strains belonging to serotype O29:H21
      were analyzed for the presence of colonization factor antigens (CFA). 2. CFA/IV
      was detected in all twelve strains studied, and immunological analysis
      demonstrated that it was composed of coli surface antigens 5 (CS5) and 6 (CS6)
      presenting molecular weights of approximately 21 kDa and approximately 16 kDa,
      respectively. 3. CS6 antigenic homology was observed between O29:H21 and
      reference strains E11881C and E17018A. 4. CS6 of the O29:H21 strains was composed
      of two peptide bands, similar to the reference strain E17018A.

PMID- 8136727
TI  - Cloning of the Escherichia coli radC gene: identification of the RadC protein.
AB  - 1. The DNA sequence of the radC gene suggests an open reading frame of 297-bp. 2.
      To identify the gene product, radC was subcloned in an expression vector, pKK223
      3 and the RadC protein identified by the maxicell method as a polypeptide of
      approximately 11 kDa.

PMID- 8136728
TI  - Risk factors for development of proteinuria by type II (non-insulin dependent)
      diabetic patients.
AB  - 1. Renal involvement in non-insulin dependent diabetes mellitus patients is the
      single most important cause of renal failure. The aim of this study was to
      evaluate the clinical features and to assess the risk factors for the development
      of proteinuria by non-insulin dependent diabetic patients. 2. Risk factors
      (expressed as an odds ratio) were calculated by multiple logistic regression
      analysis taking into account age, sex, body mass index, known duration of
      diabetes, presence of arterial hypertension, fasting plasma glucose, cholesterol
      and triglycerides as independent variables and proteinuria as the dependent
      variable. Sixty-four normoalbuminuric (24-h albumin excretion rate < 30
      micrograms/min, 27 females, mean age 53.7 years) and 53 proteinuric (24-h
      proteinuria > 0.5 g, 31 females, mean age 59.3 years) were studied. 3.
      Proteinuric patients were older, with a longer mean known duration of diabetes
      (12.4 vs 5.6 years), higher mean fasting plasma glucose (214 vs 168 mg/dl) and
      plasma creatinine (1.5 vs 1.1 mg/dl) and more frequently presented diabetic
      retinopathy (94% vs 23%), peripheral neuropathy (94% vs 23%) and arterial
      hypertension (73% vs 16%) than normoalbuminuric patients. Age > 50 years, body
      mass index > 28.6 kg/m2, known duration of diabetes > 10 years, presence of
      arterial hypertension, and fasting plasma glucose > 160 mg/dl were significantly
      and independently associated with development of proteinuria.

PMID- 8136730
TI  - Effects of crustacean hyperglycemic hormones from Carcinus maenas and Orconectes
      limosus on blood and muscle glucose and glycogen concentration of Chasmagnathus
      granulata.
AB  - The effects of purified crustacean hyperglycemic hormones (CHH) from Carcinus
      maenas or Orconectes limosus, and of eyestalk extract of Chasmagnathus granulata
      on the blood and muscle glucose and glycogen concentration of Chasmagnathus
      granulata were investigated. Different groups of animals (at least 7 animals per
      group) were injected with CHH from either C. maenas or O. limosus CHH dissolved
      in saline (16 pmol/animal) or crude eyestalk extract of C. granulata (1 eyestalk
      equivalent/animal). All injections had a volume of 10 microliters. Blood and
      muscle glucose and glycogen concentrations were determined immediately before the
      injections and after 30, 60 and 120 min. CHH administration from both species, as
      well as eyestalk extract, resulted in marked hyperglycemia. However, their
      effects were different. CHH from C. maenas also caused a decrease in the glycogen
      concentration of blood (from 89.8 +/- 4.3 to 76.6 +/- 3.1 mg/100 ml) and muscle
      (from 7.9 +/- 0.8 to 4.0 +/- 0.7 mg/g) and glucose concentration of muscle (from
      2.4 +/- 0.3 to 1.2 +/- 0.2 mg/g). CHH from O. limosus caused an increase of
      glycogen concentration of muscle (from 4.9 +/- 1.1 to 9.0 +/- 1.1 mg/g). The
      injection of eyestalk extract resulted also in a decrease of hemolymph glycogen
      (from 157.7 +/- 20.6 to 30.2 +/- 7.7 mg/100 ml). Therefore, C. granulata may have
      different receptors for CHH in its different tissues, and/or in the same tissue,
      which act through different metabolic pathways to achieve the same final result,
      i.e., hyperglycemia.

PMID- 8136729
TI  - Histology of the mucosa of gastric antrum and body before and after eradication
      of Helicobacter pylori.
AB  - 1. Helicobacter pylori status and the histology of the antral and oxyntic mucosa
      were evaluated in 25 patients with duodenal ulcer treated with a triple schedule
      of furazolidone, metronidazole and amoxicillin, and in 16 patients treated only
      with cimetidine. 2. Before treatment, H. pylori was detected in all patients. One
      month after treatment with the antimicrobial agents, H. pylori was not found in
      18 (72.0%) of 25 patients treated with the triple schedule. In the patients
      treated with cimetidine (N = 16) the H. pylori tests continued to be positive
      after treatment. 3. Inflammatory activity and intensity of gastritis were
      significantly reduced in patients treated with the antimicrobial agents but not
      in cimetidine-treated patients. Three patients who had negative cultures and
      improvement of gastritis 1 month after treatment became H. pylori positive again
      within 2 months, with concomitant reappearance of gastritis. 4. This study
      provides additional evidence that histological gastritis observed in H. pylori
      positive patients with duodenal ulcer is due to the presence of the
      microorganism.

PMID- 8136731
TI  - Effect of dietary iron on the course of Plasmodium berghei malaria in young rats.
AB  - Clinical and experimental evidence suggests that iron-deficient hosts are less
      susceptible to severe malaria and that iron supplementation aggravates infection.
      In the present study, 60 weanling Wistar rats were fed standard diets with
      different iron concentrations: 21 mg/kg (group 1), 45 mg/kg (group 2) and 113
      mg/kg (group 3). Ferrous sulfate (FeSO4 x 7H2O) was added to the normal-iron and
      iron-supplemented diets (groups 2 and 3, respectively). Data are reported as mean
      +/- SEM. After 16 days of regimen, eight rats from each group were killed to
      measure serum iron concentration (SI) and transferrin saturation capacity (TSC).
      At this moment, rats from group 1 were underweight and their dietary intake was
      significantly lower than that of animals from the other groups. Severe iron
      deficiency (SI = 49.2 +/- 4.5 micrograms/100 ml and TSC = 8.3 +/- 0.7%) was
      observed in rats from group 1, while the animals from the other groups were iron
      sufficient (group 2: SI = 186.5 +/- 28.5 micrograms/100 ml and TSC = 27.3 +/-
      3.4%; group 3: SI = 137.3 +/- 18.2 micrograms/100 ml and TSC = 21.3 +/- 2.3%).
      Nine animals from each group were then infected with the malaria parasite
      Plasmodium berghei, whereas three animals from each group were used as
      noninfected controls. Parasitemias (% of infected red blood cells) peaked 7 days
      post-infection in animals from groups 2 and 3 (mean values of 2.4% and 1.7%,
      respectively), but in animals from group 1 parasitemias increased until the 9th
      day post-infection (mean at peak, 2.3%) and parasite clearance was significantly
      slower than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136732
TI  - Preparation of human rabies vaccine in VERO cell culture using a microcarrier
      system.
AB  - 1. The rabies virus (Pasteur PV strain) was propagated in VERO cells attached to
      microcarriers in a 3.7-1 bioreactor. Virus titers of about 10(6) LD50/ml were
      obtained regularly. 2. Ultrafiltration was efficient for concentrating the virus
      suspensions, and the sucrose gradient reduced the residual VERO cell DNA to
      acceptable levels (less than 50 pg/dose). The remaining cell DNA content was
      evaluated by dot-blot hybridization with a probe prepared with VERO cell DNA. 3.
      The final virus preparations were inactivated by B-propiolactone treatment,
      showed a potency higher than 2.5 IU/dose and protected mice experimentally
      infected intracerebrally with rabies virus (CVS-13.2). 4. This methodology for
      the production of a rabies vaccine for human use should be of interest to
      countries where high technology facilities are not available.

PMID- 8136733
TI  - Taurine modulates chemical nociception in mice.
AB  - The effect of taurine on nociception was investigated in adult male Swiss mice
      using the formalin and acetic acid tests. Taurine (50-200 mg/kg) injected sc into
      the animals (N = 6 per group) 30 min before formalin injection into the right
      hind paw reduced formalin-induced early phase (0-5 min) licking activity by 30
      42%, but had no effect on the late phase (20-25 min) response. Writhing responses
      induced by acetic acid injected ip were also significantly inhibited by 49% and
      56% by doses of 100 and 200 mg/kg taurine, respectively. In both tests taurine
      demonstrated antinociception which was significantly blocked by naloxone (1
      mg/kg, sc, administered simultaneously with taurine). The naloxone-sensitive
      antinociceptive action of taurine was probably mediated via modulation of
      endogenous pain-regulatory systems that involve opioid peptides, neuropeptides
      like substance P and amino acids such as glutamate and aspartate.

PMID- 8136734
TI  - Evidence for the participation of the L-arginine-nitric oxide pathway in neurally
      induced relaxation of the isolated rat duodenum.
AB  - 1. Electrical field stimulation (EFS) of intrinsic nerves in the rat proximal
      duodenum induces a frequency-dependent non-adrenergic-non-cholinergic (NANC)
      relaxation response. 2. The inhibitors of L-arginine-NO synthase L-NG-nitro
      arginine methyl-ester (L-NAME) and L-NOARG (L-NG-nitro arginine) reduced the NANC
      relaxations elicited by EFS in a dose- and time-dependent manner; L-NOARG was two
      times more potent than L-NAME (IC50 = 14.3 vs 25.2 microM) and these effects were
      partially reverted by the addition of 300-1000 microM L-arginine but not of 300
      1000 microMD-arginine. Relaxation caused by vasoactive intestinal peptide (VIP;
      0.1 microM) or ATP (20 microM) was not blocked by L-NAME or L-NOARG. 3. The
      magnitude of the blockade caused by L-NAME and L-NOARG was dependent on the
      frequency of stimulation. At low frequencies (below 1 Hz) both L-NAME and L-NOARG
      abolished the relaxations, while at 2 to 8 Hz only partial inhibition was
      observed (maximal inhibition: 44.6% +/- 5.2 and 63.4% +/- 3.4, respectively) 4.
      The basal tonus of the duodenum was increased by 10-300 microM L-NAME and 10-300
      microM L-NOARG and this effect was blocked by 1 mM L-arginine. 5. Nitric oxide
      generated from acidified NaNO2 caused a dose-dependent (EC50 = 2.75 microM)
      relaxation of the duodenum which was not affected by 100 microM L-NAME, 100
      microM L-NOARG or 1 microM tetrodotoxin (TTX). 6. NADPH-diaphorase positive
      neurons and fibers identified by histochemistry were present in the myenteric
      plexus and along both circular and longitudinal muscle fibers indicating that
      nitric oxide could be synthetized by these neural structures.

PMID- 8136735
TI  - Neural and humoral mechanisms involved in the generation of arterial pressure
      lability in rats.
AB  - 1. The role of the renin-angiotensin system (RAS) and sympathetic nervous system
      (SNS) in the generation of the arterial pressure lability (APL) observed after
      sino-aortic deafferentation (SAD) in rats was evaluated. 2. SAD was performed in
      normotensive (N = 8), renal hypertensive (2K-1C, N = 8) and spontaneously
      hypertensive rats (SHR, N = 8) and mean arterial pressure (MAP) recordings were
      performed 24 h after SAD. 3. MAP was recorded by a computerized technique using a
      sampling frequency of 30 Hz for 30 min and the data obtained were used to
      calculate APL. After MAP measurements the activity of the RAS and SNS was
      pharmacologically evaluated in all groups by the changes in MAP in response to iv
      injection of captopril and hexamethonium chloride, respectively. 4. SAD produced
      an increase in MAP (118 +/- 4 vs 99 +/- 2 mmHg) and a large increase in APL (13.4
      +/- 1.3 vs 3.8 +/- 0.3 mmHg) in normotensive rats. SAD produced no changes in MAP
      (161 +/- 7 vs 167 +/- 7 mmHg) in 2K-1C hypertensive rats but induced a large
      increase in APL (6.7 +/- 0.5 vs 12 +/- 1 mmHg). SAD also produced no changes in
      MAP (152 +/- 3 vs 152 +/- 4 mmHg) in SHR but induced a marked increase in APL
      (6.7 +/- 0.3 vs 21 +/- 2.3 mmHg). 5. All SAD rats presented a larger fall in MAP
      in response to captopril and hexamethonium than the respective control group with
      intact baroreceptors suggesting an overactivity of both systems after SAD in
      normotensive, renal hypertensive and spontaneously hypertensive rats. 6. The data
      also show that SAD produced no additional increase in MAP but promoted a
      significant increase in APL in renal and spontaneously hypertensive rats. 7. We
      suggest that APL observed after SAD in different experimental models is dependent
      on an interaction of RAS and SNS, both of which seem to be overactive after
      removal of arterial baroreceptors.

PMID- 8136736
TI  - Paradoxical effect of neuromedin B and thyroxin on thyrotropin secretion from
      isolated hyperthyroid pituitaries.
AB  - Neuromedin B (NB) is a bombesin-like peptide that we recently characterized as a
      physiological autocrine inhibitor of thyrotropin (TSH) secretion. We now report
      the effect of NB, thyroxin (T4) and NB + thyroxin on basal and THR (50 nM)
      stimulated TSH release from isolated hemipituitaries of hyperthyroid rats. To
      induce hyperthyroidism, 20 rats were treated with 0.03% methimazole for one month
      and then received T4, 4 micrograms/100 g body weight, sc, daily for 7 days. Each
      experimental group consisted of 7 to 9 hemipituitaries. TSH was measured using a
      rat TSH kit provided by NIDDK. Basal TSH release was paradoxically increased in
      the presence of 0.1 microM T4 or 0.1 microM NB and even two times higher in the
      presence of both (Control: 30.0 +/- 4.2 ng/ml; T4: 58.6 +/- 5.6 ng/ml; NB: 53.4
      +/- 6.1 ng/ml; T4 + NB: 90.4 +/- 8.5 ng/ml). The percent increment above basal
      TSH levels after TRH was higher only in the presence of NB (Control: 44.5 +/-
      8.2%, NB: 105.3 +/- 18.8%; P < 0.05). Altered responsiveness in hyperthyroidism
      and direct modification of the intracellular metabolism of T4 are mechanisms that
      could explain this paradoxical effect.

PMID- 8136737
TI  - Blockade of the 32P phosphate flush of pancreatic beta cells from adult rats who
      received a low-protein diet during early lactation.
AB  - In order to study the effect of nutrition on the onset of disturbances in Wistar
      rat pancreatic beta cells, we compared the effects of a low protein diet (8%
      protein) and a normal protein diet (25% protein) supplied to the dams (6 in each
      group) during the first 12 days of lactation. The parameter evaluated was the
      beta cells phosphate flush in response to stimulatory concentration of glucose
      (16.7 mM) of isolated islets of Langerhans from 60-day old pups. Using a
      collagenase digestion technique, islets were isolated from the pups and the 32P
      fractional outflow rate (FOR) of the beta cells was used as a metabolic index in
      both experimental groups (N = 36). We observed that although the weights of the
      pups of the two groups were not significantly different at 60 days of age
      (control = 186 +/- 18 g; undernourished during lactation = 179 +/- 19 g), the
      typical phosphate flush response (FOR = 2.4 +/- 0.4%/min) to a stimulatory
      glucose concentration (16.7 mM) was abolished in the rats from undernourished
      mothers. Our data are consistent with the hypothesis that undernutrition may be
      an important cause of diabetes mellitus type II.

PMID- 8136738
TI  - Interleukin-1 and tumor necrosis factor-alpha as radio- and chemoprotectors of
      bone marrow.
AB  - Administration of interleukin 1 (IL-1) or tumor necrosis factor-alpha (TNF alpha)
      protects bone marrow precursor cells (BMPC) from ionizing radiation and
      antineoplastic drugs. The time of injection is critical: the best protective
      results being obtained when cytokines are given around 24h prior to the induced
      injury. Multiple daily cytokine injections that precede irradiation or drug
      administration are more effective than single ones although single doses are
      quite effective at increasing survival in mice. Protection is positively
      correlated with both rapid granulocyte recovery and BMPC survival. Mechanisms
      involved in BMPC radioprotection include: (1) push to the S/G2 + M or arrest in
      the G0 phases of the cell cycle by IL-1 or TNF alpha, respectively, and (2)
      induction of mitochondrial manganous superoxide dismutase synthesis. For BMPC
      chemoprotection, proposed mechanisms are: (1) increase of aldehyde dehydrogenase
      synthesis, and (2) modulation of multiple-drug resistant gene expression.
      Stimulation of glutathione synthesis in BMPC could be operating in both radio-
      and chemoprotection. These findings point to the relevance of IL-1 or TNF alpha
      in cancer therapy as a means of reducing BMPC sensitivity to cytoreductive drugs
      or irradiation (including radioimmunotherapy) as well as in in vitro tumor cell
      purging with drugs in autologous BMT. Prior administration of these cytokines
      should be also considered for people in imminent danger of exposure to radiation.

PMID- 8136739
TI  - Coactivation with anti-CD28 monoclonal antibody enhances anti-CD3 monoclonal
      antibody-induced proliferation and IL-2 synthesis in T cells from autologous bone
      marrow transplant recipients.
AB  - Recent studies show that costimulation of T cells with anti-CD28 Mab (anti-CD28)
      enhances anti-CD3 Mab (anti-CD3)-induced proliferative responses and cytokine
      production. This study determines if coactivation with anti-CD3 and anti-CD28
      corrects defects in proliferation and IL-2 secretion in peripheral blood
      lymphocytes (PBL) from bone marrow transplant (BMT) recipients. PBL or T cells
      from 5 of 16 autologous and 5 of 22 allogeneic recipients increased their anti
      CD3-induced proliferation responses by > 50% after coactivation. In short-term (<
      180 days after BMT) autologous recipients, the group mean response increased
      after anti-CD3 activation from 62,900 to 97,800 cpm after coactivation. In long
      term (> 180 day after BMT) autologous recipients, the group mean response after
      anti-CD3 activation increased from 62,600 to 78,400 cpm after coactivation. The
      long-term autologous recipient group had costimulated responses from PBL that
      were significantly higher than the paired anti-CD3-induced responses (p < 0.01);
      in contrast, such differences were not seen in allogeneic recipient groups. After
      anti-CD3 stimulation, the mean response of 88,000 cpm for PBL from short-term
      allogeneic recipients and the mean response of 83,600 cpm for PBL from long-term
      allogeneic recipients were higher than those in PBL from autologous recipients
      were higher than those in PBL from autologous recipient groups. The amount of IL
      2 secreted by T cells from three autologous and three allogeneic recipients was
      enhanced 0.9-25-fold by coactivation. Coactivation of PBL from selected
      recipients increased proliferation into the normal range and increased IL-2
      secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136740
TI  - Virus recovery from stools of patients undergoing bone marrow transplantation.
AB  - Diarrhea in marrow transplant recipients is a frequent complication attributable
      to non-infectious events such as acute GVHD or infectious events such as viral
      gastroenteritis. Rotavirus and enteric adenovirus are the most frequent viral
      pathogens. To determine the frequency of these infections, we prospectively
      examined the stool specimens of 94 patients who underwent autologous BMT (34
      cases) or allogeneic BMT (60 cases). Stool specimens were examined from patients
      twice weekly. Nineteen of the 94 patients were infected with viral pathogens.
      This study showed: (1) an incidence of viral gastroenteritis identical in
      autologous and allogeneic BMT (20%), (2) a persistent risk despite treatment in
      laminar air flow rooms, (3) a significant association with severe acute GVHD, and
      (4) a significant risk of multiple viral infections in autologous BMT recipients.
      Rotavirus and adenovirus are a cause of enteritis involvement in patients
      undergoing BMT and they may be underdiagnosed and confused with GVHD. Screening
      of stool specimens after BMT should be directed to prevention and treatment of
      these viral infections to decrease the morbidity and mortality associated with
      BMT.

PMID- 8136741
TI  - Randomized double-blind study of liposomal amphotericin B (Ambisome) prophylaxis
      of invasive fungal infections in bone marrow transplant recipients.
AB  - Invasive fungal infection is a problem in patients undergoing bone marrow
      transplantation (BMT). To determine if a liposomal formulation of amphotericin B
      (Ambisome) is safe and can prevent fungal infection we performed a placebo
      controlled double-blind randomized prophylactic trial. Study drug was
      administered from when neutrophil count had decreased to < 0.5 x 10(9)/l and was
      continued until neutrophils recovered to this level or an infection or toxicity
      end-point was reached. Thirty-six patients received 1 mg/kg/day of ambisome and
      40 patients received placebo daily. There were no statistical differences in
      characteristics or clinical course between the two groups. Fungal colonization
      decreased in the ambisome group while it increased in the placebo group. By the
      end of prophylaxis 8 of 24 (33%) patients receiving ambisome were colonized
      compared with 18 of 29 (62%) placebo patients (p = 0.05). Five and 7 patients on
      ambisome or placebo, respectively, were withdrawn due to a presumed fungal
      infection (NS). There was no statistical reduction of autopsy-proven fungal
      infection. Proven fungal infection occurred in one patient receiving ambisome (C.
      guillermondi) compared with three patients receiving placebo (C. guillermondi, 2;
      C. albicans, 1). Ambisome was well tolerated at the dose of 1 mg/kg/day but in
      three patients allergic reactions were observed.

PMID- 8136742
TI  - Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in
      first complete remission: factors predictive of transplant-related mortality and
      influence of total body irradiation modalities.
AB  - In a retrospective multicentre study, we analyzed 184 consecutive patients who
      underwent bone marrow transplantation (BMT) from identical siblings for adult
      acute lymphoblastic leukemia in first complete remission between March 1980 and
      May 1989. The main causes of transplant-related mortality were GVHD and
      interstitial pneumonitis. Univariate and multivariate analyses identified the
      mode of total body irradiation (TBI) as the only independent predictive factor of
      transplant-related mortality. Ninety-one patients received single-dose TBI and 93
      received fractionated-dose TBI as part of the conditioning regimen prior to BMT.
      Transplant-related mortality was more frequent in the single dose group (p =
      0.017). The incidence of interstitial pneumonitis, acute and chronic GVHD and
      veno-occlusive disease of the liver was not statistically different between the
      two irradiation groups. However, fatal interstitial pneumonitis was significantly
      more frequent in the single dose irradiation group (p = 0.031). These results
      show that transplant-related mortality is closely associated with the mode of TBI
      administration. The increased relapse rate in the fractionated group explains why
      there was no difference between the two groups in terms of overall leukemia-free
      survival.

PMID- 8136743
TI  - Allogeneic bone marrow transplantation for poor-prognosis non-Hodgkin's lymphoma.
AB  - Twenty-one patients with non-Hodgkin's lymphoma (NHL) felt to be incurable with
      conventional chemotherapy underwent high-dose chemo +/- radiotherapy and
      allogeneic sibling donor transplant. The median patient age was 27 years (range 6
      47 years); 13 were male and 8 female. By the working formulation, 6 patients at
      diagnosis had low-grade NHL, 8 intermediate-grade, and 7 high-grade disease.
      Three patients were in first remission at transplant, 3 in an advanced remission,
      5 had failed to respond to initial therapy while 4 had a partial response to
      initial therapy, and 6 were in relapse (first or beyond). Sixteen patients were
      conditioned with cyclophosphamide, etoposide and total body irradiation (TBI), 4
      with cyclophosphamide and TBI, and one with a combination of busulfan, melphalan
      and cyclophosphamide. GVHD prophylaxis was variable. At last follow-up, 8 of 21
      patients remain alive and progression-free at a median of 37.5 months (range 6-58
      months); actuarial event-free survival is 38% (95% confidence interval 17-58%).
      Thirteen patients died at a median of 2 (range 0.5-8) months post-BMT, 5 from
      regimen-related toxicity, 3 from acute GVHD, 2 from infections related to chronic
      GVHD and 3 from disease progression. Factors which were adverse predictors of
      progression-free survival included low-grade disease, presence of B symptoms at
      BMT, Karnofsky performance status at BMT and female sex. We concur with previous
      workers in concluding that allogeneic BMT may offer effective therapy for
      selected patients with incurable NHL. Major issues to be considered include
      timing of BMT and disease status at BMT.

PMID- 8136745
TI  - Changes in cell and protein content of cerebrospinal fluid in children with acute
      lymphoblastic leukaemia after allogeneic bone marrow transplantation.
AB  - The material from 59 and 134 cerebrospinal fluid (CSF) samples, taken in the week
      prior to grafting and during the first 100 days after grafting respectively, were
      examined from 37 children undergoing allogeneic BMT. All CSF samples were
      obtained from lumbar punctures performed for regular administration of
      methotrexate (MTX). Prior to bone marrow transplantation (BMT) the increased
      protein levels and increased cell numbers noted in two children were probably
      caused by arachnoiditis from MTX administration 5 days earlier. After BMT, cell
      numbers increased in 54% of children and in 27% of children increased protein
      levels were found in the CSF. No correlation with clinical findings including
      neurological findings, infections and prior intrathecal MTX administration was
      found. The CSF changes observed are probably induced by the conditioning regimen
      (i.e. cyclophosphamide and total body irradiation). We conclude that the normal
      ranges for CSF components seen in healthy individuals do not apply in BMT
      recipients during the first 100 days after grafting.

PMID- 8136744
TI  - Fractionated total body irradiation and high-dose VP-16 with purged autologous
      bone marrow rescue for children with high risk relapsed acute lymphoblastic
      leukemia.
AB  - Twenty-two children with ALL in high risk second (n = 13), third or subsequent
      complete remission (n = 9) were treated with high-dose VP-16 60 mg/kg and
      fractionated total body irradiation (fTBI) 12 Gy, 2 x 2 Gy daily followed by
      autologous BM rescue. Prior to transplantation all patients had been treated
      according to intensive German BFM front-line or BFM relapse protocols. In all
      cases the marrow was purged using monoclonal antibodies attached to magnetic
      microspheres. All patients engrafted. There was no severe toxicity related to the
      pre-transplant high-dose chemoradiotherapy. Two patients died in the early course
      of transplantation from infections (Legionella and Aspergillus). Sixteen patients
      relapsed within 259 days (median 109 days); 13 died from leukemia. Four patients
      are alive in CR at a median of 1328 days with a Karnofsky score of 100%. The
      Kaplan-Meier estimation shows a probability of event-free survival (EFS) of 18%
      and a probability of relapse of 80%. Considering the otherwise poor prognosis of
      these children the results are acceptable although the high relapse rate is still
      disappointing. We conclude that high-dose VP-16 and fTBI combined with ABMT is a
      curative treatment for some children and should therefore be considered for those
      who lack an HLA-identical sibling donor. In future better therapy concepts are
      needed either in pre-transplant conditioning regimens or in post-transplant
      treatment schedules.

PMID- 8136746
TI  - Graft-versus-host disease in children: the AIEOP-BMT Group experience with
      cyclosporin A.
AB  - We retrospectively analyzed the data base of the Italian Association of Pediatric
      Hematology/Oncology BMT Group on the incidence and severity of GVHD in children
      given allogeneic BMT from HLA-identical sibling and receiving cyclosporin A (CsA)
      alone as GVHD prophylaxis. The study population included 145 patients for acute
      GVHD and 114 children at risk for chronic GVHD. Twelve patients had non-malignant
      diseases and 133 patients were affected by malignant disorders. Among the 145
      patients (50 females, 95 males), 107 (74%) presented acute GVHD and 38 (26%) had
      no sign of disease. In the group of patients with acute GVHD, 38 children (26% of
      the whole study population) were found to have grade II disease, 9 (6% of the
      whole) grade III, 4 (3%) grade IV. Donor-recipient sex pairs had no significant
      influence on incidence of acute GVHD neither did donor-recipient age class
      stratification. Of the 114 patients evaluated for chronic GVHD, 86 (76%)
      developed no disease while 23 patients (20%) presented secondary chronic GVHD and
      5 (4%) had de novo chronic GVHD. The incidence of chronic GVHD was higher in F-M
      than in M-M donor-recipient sex pairs (33% vs 11%, p < 0.05), with no difference
      between F-F and M-F. In patients of > 10 years, a higher incidence of chronic
      GVHD was observed in both female donors and recipients compared with male donors
      and recipients (48% vs 20% and 47% vs 19%, respectively, p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8136747
TI  - Monitoring cytokine production in peripheral blood during acute graft-versus-host
      disease following allogeneic bone marrow transplantation.
AB  - Plasma concentrations and peripheral blood cells containing cytoplasmic cytokines
      were monitored during the post-transplant period in 10 patients who had received
      allogeneic bone marrow transplants (BMT) for the correction of inherited genetic
      disorders. The presence of CD14-positive cells containing cytoplasmic interleukin
      1 alpha and beta in the peripheral blood was indicative of acute graft-versus
      host disease (GVHD). Plasma concentrations of IL-1 alpha, IL-1 beta and TNF-alpha
      were significantly raised in the GVHD group when compared with the uneventful
      days. There was, however, poor temporal correlation between the plasma
      concentrations and clinical manifestations of acute GVHD. Cells containing
      cytoplasmic IL-6 were present in the peripheral blood when patients had
      clinically suspected and/or microbiologically confirmed infection. The results
      from this study demonstrate that analysis of peripheral blood cells for
      cytoplasmic IL-1 alpha and IL-1 beta are better markers of acute GVHD than is
      monitoring plasma concentrations of these cytokines.

PMID- 8136748
TI  - Minimal residual disease after bone marrow transplantation for multiple myeloma:
      evidence for cure in long-term survivors.
AB  - Allogeneic bone marrow transplantation (BMT) can induce long-term complete
      remission (CR) in patients with multiple myeloma but it is not yet clear whether
      the disease can be eradicated. We have used immunoglobulin gene fingerprinting, a
      PCR-based technique, to evaluate minimal residual disease in 5 patients in
      unmaintained CR 9-60 months after allogeneic BMT. All 5 patients were PCR
      positive within the first year after BMT, suggesting that early PCR positivity is
      common and not predictive of relapse. Three patients were studied at > 1 year
      post-transplant; one had become PCR-negative at 1 year, a second at 2 years and
      the third at 4.5 years post-BMT. The ability of the technique to detect clonal
      evolution was demonstrated by serial studies in a further patient who relapsed
      post-BMT. The absence of any detectable disease at the molecular level in 3
      patients in long-term CR post-transplant suggests that cure of multiple myeloma
      may be a realistic goal.

PMID- 8136749
TI  - Allogeneic bone marrow transplantation following busulfan and 90 mg/kg of
      cyclophosphamide.
AB  - Ten patients with AML or CML aged 40-55 years underwent allogeneic marrow
      transplantation from HLA-identical siblings following a preparation regimen of
      busulfan 16 mg/kg and cyclophosphamide (CY) 90 mg/kg. The CY dose was
      substantially lower than has been previously used in combination with busulfan.
      All 10 individuals engrafted. Cytogenetic analysis of marrow and peripheral blood
      cells demonstrated similar patterns of chimerism to those previously described
      using higher CY doses. This study demonstrates that when administered with
      busulfan 16 mg/kg a dose of 90 mg/kg CY is adequately immunosuppressive to permit
      consistent engraftment of marrow from HLA-identical sibling donors.

PMID- 8136750
TI  - Successful pregnancy in a 28-year-old patient autografted for acute lymphoblastic
      leukemia following myeloablative treatment including total body irradiation.
AB  - We report a successful pregnancy in a woman who at the age of 28 years received
      total body irradiation (TBI; 7.5 Gy) and high-dose chemotherapy prior to
      autografting of purged bone marrow for acute lymphoblastic leukemia. Four years
      after transplantation she delivered a healthy girl. Only five previous cases of
      successful pregnancies are described in the literature after conditioning
      regimens including TBI. This case shows that restored ovarian function is
      possible after TBI in spite of prolonged exposure to chemotherapeutic agents
      during induction and consolidation therapy and relatively high age at the time of
      transplantation.

PMID- 8136751
TI  - Rapid detection of engraftment using T cell receptor gene polymorphism after
      allogeneic bone marrow transplantation in an alloimmunized child with severe
      aplastic anemia.
AB  - A severely alloimmunized boy with aplastic anemia received an HLA-identical BMT
      from his brother. Despite intensive immunosuppression and large marrow dose,
      peripheral signs of engraftment occurred only late under G-CSF treatment. With
      leukocyte counts of < 0.5 x 10(9)/l, chimerism could be proven not only by
      oligonucleotide fingerprinting but also within 48 h by analysis of polymorphism
      in the TCR gene family. This rapid and sensitive method to detect engraftment
      before it became quantitatively evident was important for the clinical management
      of the patient, obviating the need to search for an alternative marrow donor.

PMID- 8136752
TI  - Second autologous bone marrow transplantation in Hodgkin's disease.
AB  - We report a case of sustained disease-free survival following second autologous
      marrow transplantation (BMT) in a patient with Hodgkin's lymphoma which had
      recurred following several conventional chemotherapy regimens as well as a prior
      autologous transplant. The initial autologous BMT was performed in fourth
      complete remission and followed high-dose cyclophosphamide, etoposide and
      thiotepa. The disease recurred 8 months later and the patient underwent a second
      ABMT following conditioning with busulfan and cyclophosphamide 1 year after his
      first transplant. Aside from slow engraftment, his course was uncomplicated. This
      patient remains in complete remission more than 4 years and 6 months following
      the second transplantation. This case demonstrates that second autologous
      transplantation can result in sustained disease-free survival in individuals with
      Hodgkin's disease with recurrence following initial transplantation.

PMID- 8136753
TI  - Allogeneic bone marrow transplantation combined with multiple anti-HIV-1
      treatment in a case of AIDS.
AB  - A 25-year-old woman with AIDS was submitted to HLA-identical allogeneic BMT after
      cytoablation with busulphan and cyclophosphamide and combined anti-HIV-1 therapy
      with zidovudine, IFN-alpha 2 and anti-HIV-1-specific T cell clones. Marrow
      engraftment occurred after 18 days and tests for HIV-1 were negative after 30
      days but the hematologic reconstitution of the patient was poor. A second BM
      infusion from the same donor was ineffective and treatment with GM-CSF only
      induced a transient increase of the blood cell count, suggesting iatrogenic
      damage to the BM microenvironment. The development of ARDS led to the death of
      the patient 10 months after transplantation. Post-mortem investigation did not
      reveal any active infections and PCR on autopsy tissues was negative for HIV-1.

PMID- 8136754
TI  - From Index Catalogue to Gopher space: changes in our profession as reflected in
      the Handbook and CPHSL.
AB  - A fifty-year review of the history of health sciences librarianship, as reflected
      in four editions of the Handbook of Medical Library Practice and its successor,
      Current Practice in Health Sciences Librarianship, illustrates the significant
      changes our profession has undergone. Publication in 1943 of the first edition of
      the Handbook marked an important milestone in the development of the Medical
      Library Association, as a group of dedicated volunteers documented standard
      practice and recorded useful data. Administration of health sciences libraries
      has moved from art to science. Responsibility for the development of collections
      is now the sole purview of professional librarians. Automation and bibliographic
      standards have revolutionized the methods for controlling and providing access to
      information resources. And, the means by which assistance is provided to library
      users, through the use of computer and telecommunications technology, has changed
      dramatically.

PMID- 8136755
TI  - Megatrends for the information age.
AB  - The 1990s are a decade characterized by change. Technological advances and health
      care reform are changing the demand for and provision of biomedical information,
      while political, economic, and social change are transforming the larger
      environment. There are four important megatrends shaping the global future: the
      new world order, the renaissance of the arts, the triumph of the individual, and
      the decade of women in leadership. Preparing to take advantage of the
      opportunities created by these changes is essential for organizations to survive
      and for individuals to become leaders.

PMID- 8136756
TI  - Growth patterns in the National Library of Medicine's serials collection and in
      Index Medicus journals, 1966-1985.
AB  - Data from the National Library of Medicine (NLM) automated Master Serials System
      and its MEDLINE database were used to chart the growth of NLM's serials
      collection and of the journals indexed in Index Medicus from 1966 to 1985. The
      number of live serial titles in the subset of NLM's collection examined increased
      30% in the twenty years. The average number of articles per Index Medicus journal
      increased 56%. The average number of articles in U.S. Index Medicus journals grew
      more rapidly than the average number in journals published elsewhere. The NLM
      data provide clear evidence that the years from 1966 to 1985 saw a substantial
      increase in the percentage of the biomedical serial literature published in
      English. The period from 1966 to 1985 saw substantial but uneven growth in the
      number of serial titles in the NLM collection and in the average number of
      articles in Index Medicus journals. Although data on the number of articles
      published in Index Medicus journals is unlikely to reflect the number of articles
      in other journals, the pattern of growth in the number of serials held by NLM
      probably reflects trends in the universe of all biomedical serials.

PMID- 8136757
TI  - Selecting CD-ROM databases for nursing students: a comparison of MEDLINE and the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL).
AB  - With the introduction of the Cumulative Index to Nursing and Allied Health
      Literature (CINAHL) on CD-ROM, research was initiated to compare coverage of
      nursing journals by CINAHL and MEDLINE in this format, expanding on previous
      comparison of these databases in print and online. The study assessed search
      results for eight topics in 1989 and 1990 citations in both databases, each
      produced by SilverPlatter. Results were tallied and analyzed for number of
      records retrieved, unique and overlapping records, relevance, and
      appropriateness. An overall precision score was developed. The goal of the
      research was to develop quantifiable tools to help determine which database to
      purchase for an academic library serving an undergraduate nursing program.

PMID- 8136758
TI  - Survey on the use of information sources in the field of aging.
AB  - This article presents the results of a survey conducted over the summer of 1992
      on the use of information sources by professionals in the field of aging. In
      particular, factors affecting the use of electronic information sources were
      investigated. The data provide a demographic profile of North American
      gerontologists, with a predictably wide range of disciplines and types of
      practice represented. Several factors were found to have an impact on the
      gerontologists' utilization of electronic information sources. Respondents who
      used a larger-than-average number of computer applications were found to make
      relatively more use of electronic sources, including online searches, CD-ROM
      indexes, library OPACs, and other databases searched by remote access. Attendance
      at library workshops was found to increase the amount of end-user searching but
      not the amount of library-mediated searching. Respondents also reported which
      databases they used and which they considered most important. MEDLINE was the
      most frequently mentioned database across all disciplines, including the health
      and social sciences. Computer databases were ranked least important out of six
      listed sources of information, and only 5% of respondents reported having used an
      electronic current awareness profile.

PMID- 8136759
TI  - Physician-patient communication from the perspective of library and information
      science.
AB  - The physician-patient communication process has received little attention from
      library and information science (LIS) professionals. A limited review of other
      literature on this topic was undertaken to gain some understanding of the
      information exchange from an LIS perspective. The authors were interested in four
      issues, including how information is defined; how information-seeking behavior is
      portrayed; what barriers to information exist in the exchange process; and what
      role, if any, information plays in health outcomes. Studies have been conducted
      by researchers in various disciplines who have defined communication as a giving
      and seeking activity between the physician and the patient. Barriers to good
      communication, erected by either party or by both, prevent the participants from
      experiencing a satisfactory encounter. Because information can play a role in
      health outcomes, various strategies have been tried to improve the communication
      process. These studies provide a better understanding of the physician-patient
      encounter and suggest new areas of patient-centered research for LIS
      professionals.

PMID- 8136760
TI  - The role of the medical school-based consumer health information service.
AB  - Historically, medical information has been provided to patients at the
      physician's discretion. Although this method never has been wholly satisfactory,
      the trend toward bureaucratic organization of medical care, characterized by
      impersonal patient encounters and prompted by increased emphasis on cost
      controls, has restricted patient information even further. Yet, at the same time,
      the upsurge in consumer power has created patient demand for more health
      information. Consumers feel they have a right to expect help in obtaining
      information so they can make informed decisions with respect to their medical
      care. This paper focuses on the medical school-based consumer health service in
      this context. In particular, it calls attention to the medical school library as
      the foundation for expanded health information resources, pointing to the tools
      of information retrieval, as well as the substantive information contained in the
      medical, nursing, and allied health literature. In this setting, the consumer
      health librarian is called upon to act as a mediator in providing quality
      filtered information to the patron, while at the same time remaining within the
      confines of professional expertise as a librarian. Important sources of health
      information are highlighted, particularly online databases, drug indexes,
      therapeutic texts, and physician specialist directories.

PMID- 8136761
TI  - Providing consumer health information through institutional collaboration.
AB  - In the past several years, The Claude Moore Health Sciences Library of the
      University of Virginia Health Sciences Center (HSC) has noted a growing demand
      for consumer health information. However, because the primary role of the library
      is to provide information services to health professionals at the HSC, questions
      have been raised as to the amount of time, energy, and money that should be
      expended to provide health care information to consumers. The library staff,
      because it can provide special expertise regarding the availability and
      utilization of consumer health materials, has felt the responsibility to
      participate in HSC initiatives that reach a broad audience. Library efforts in
      that regard include assisting with inventory and management of patient education
      materials, participating in a community health promotion task force,
      collaborating with hospital departments in planning a consumer health information
      center, establishing a consumer health information reference section in the
      library, and obtaining a grant to offer a networked health information system to
      local public and community college libraries. Consumers of health information
      benefit from the enhanced services that result from combining the expertise of
      health professionals and patient educators with the information management skills
      of library staff.

PMID- 8136762
TI  - Planetree health information services: public access to the health information
      people want.
AB  - In July 1981, the Planetree Health Resource Center opened on the San Francisco
      campus of California Pacific Medical Center (Pacific Presbyterian Medical
      Center). Planetree was founded on the belief that access to information can
      empower people and help them face health and medical challenges. The Health
      Resource Center was created to provide medical library and health information
      resources to the general public. Over the last twelve years, Planetree has tried
      to develop a consumer health library collection and information service that is
      responsive to the needs and interests of a diverse public. In an effort to
      increase accessibility to the medical literature, a consumer health library
      classification scheme was created for the organization of library materials. The
      scheme combines the specificity and sophistication of the National Library of
      Medicine classification scheme with the simplicity of common lay terminology.

PMID- 8136763
TI  - A survey of patient access to hospital and medical school libraries.
AB  - The American Medical Association (AMA) Library and Information Management
      Division conducted a survey of 481 randomly selected hospital and medical center
      libraries. Data were obtained from 307 libraries (63.8%). The tabulated results
      showed that 58.1% of responding libraries allow patient access without
      restrictions. Another 19.9% allow patient access with restrictions, such as
      physician approval (13.4%) or various other limitations (6.5%). Many of the
      surveyed librarians (67%) said their institutions have separate nontechnical
      libraries for patients. Medical library access was strongly or somewhat supported
      by 89.6% of the respondents; 6.1% were somewhat opposed, and 4.3% were strongly
      opposed to patient access. Approximately 10% of the libraries surveyed provided
      no patient education forum. The AMA trustees used the results of the survey in
      deciding whether to encourage hospitals and medical schools to make their
      libraries accessible for use by patients and their families.

PMID- 8136764
TI  - Library services at health facilities in Kenya.

PMID- 8136765
TI  - Determining core journals in behavioral medicine.

PMID- 8136766
TI  - Journal Club with a mission.

PMID- 8136767
TI  - GRATEFUL MED.

PMID- 8136768
TI  - Changes: moving toward the years ahead.

PMID- 8136769
TI  - Influence of isradipine treatment on left ventricular and coronary vascular
      hypertrophy in spontaneously hypertensive rats.
AB  - The purpose of this study was to ascertain if Isradipine treatment in
      spontaneously hypertensive rats (SHR) decreased hypertension-dependent left
      ventricular and coronary vascular hypertrophy. Twelve week male SHR were used in
      this study; one group of SHR was treated with Isradipine while the control group
      of SHR was left untreated. Age-matched normotensive Wistar-Kyoto rats (WKY) were
      utilized as a reference group. After 12 weeks of treatment rats were sacrificed.
      The hearts were removed and morphometric analysis was performed on the left
      ventricles. Isradipine treatment reduced systolic blood pressure in SHR. The
      heart/body weight ratio significantly increased in SHR and in Isradipine-treated
      SHR in comparison with WKY rats. Isradipine treatment decreased the left
      ventricular muscle fibre diameter and decreased the amount of focal necrosis in
      SHR. Different sized coronary arteries were also examined using a light
      microscope and an image analyzer. We found that the area occupied by the medial
      layer and the media-to-lumen ratio were significantly increased in comparison
      with WKY rats. In Isradipine-treated SHR the area of the medial layer and the
      media-to-lumen ratio in small and medium sized but not in large sized coronary
      arteries were significantly reduced in comparison with untreated SHR. The above
      results suggest that long term Isradipine treatment is not only able to reduce
      high blood pressure in SHR but is also able to counter the development of certain
      morphological changes often seen in the hypertensive heart and coronary arteries.

PMID- 8136770
TI  - Vascular responsiveness in the unstressed borderline hypertensive rat.
AB  - This study compares vascular responses of unstressed borderline hypertensive rats
      (BHR) to age-matched Wistar-Kyoto (WKY) and spontaneously hypertensive rats
      (SHR). Rings of thoracic aorta were mounted for isometric force determinations in
      tissue baths. Cumulative additions of phenylephrine (PE) or serotonin (5-HT)
      produced contractile responses in BHR aorta that were less than WKY but greater
      than SHR. Removing the endothelium increased force development to both agonists,
      with BHR showing the greatest increase. Based on EC50 determinations, no
      differences in PE sensitivity existed between groups, although in response to 5
      HT, rings from SHR were significantly more sensitive than WKY. While the
      sensitivity of all rings increased with denuding, BHR showed a greater relative
      increase in sensitivity than WKY or SHR (intact EC50 divided by denuded EC50) to
      both PE and 5-HT. This suggests that there may be greater endothelium-derived
      relaxation in BHR than in WKY or SHR. In rings precontracted with 1 microM PE,
      the cumulative addition of acetylcholine resulted in greater relaxation in BHR
      than in SHR and WKY preparations. Thus, rings from unstressed BHR, which have
      only slightly higher blood pressures than WKY rats, demonstrate greater
      endothelium-mediated relaxation than WKY or SHR. Increased endothelium-derived
      relaxation may represent a possible mechanism for masking hypertension in BHR
      that is compromised as a result of exposure to a chronic stress paradigm.

PMID- 8136771
TI  - Phosphoinositide metabolism and aging in aorta from SHR and WKY rats: effects of
      endothelin-1 and noradrenaline.
AB  - Inositol phosphate formation in aortic rings from SHR and WKY rats of different
      ages (6, 14, and 40 weeks) was examined. Both basal and agonist (noradrenaline
      and endothelin-1) stimulated levels of inositol phosphates were studied. No
      differences in basal levels of inositol phosphate formation were observed between
      SHR and WKY nor were differences in agonist stimulated levels found in 6 week old
      animals. However, at 14 and 40 weeks both noradrenaline and endothelin-1
      stimulated levels were reduced in SHR compared to WKY. Both endothelin and
      noradrenaline stimulated inositol phosphate formation decreased with age in SHR.
      In WKY there was a decrease in endothelin but not noradrenaline stimulated levels
      with age. Age related decreases were consistently greater in SHR than WKY. Thus,
      both age and rat strain modulated agonist stimulated inositol phosphate
      formation.

PMID- 8136772
TI  - Enhanced phospholipase D activity in vascular smooth muscle cells derived from
      spontaneously hypertensive rats.
AB  - When cultured in the presence of fetal calf serum, aortic vascular smooth muscle
      cells (VSMC) derived from spontaneously hypertensive rats (SHR) grow faster than
      those from normotensive control Wistar-Kyoto (WKY) rats. In order to investigate
      the mechanism underlying this growth abnormality, we measured phospholipase D
      (PLD) activity in VSMC taken from both SHR and WKY rats. Upon stimulation with
      serum, platelet-derived growth factor (PDGF) and porbol 12-myristate 13-acetate
      (TPA), phosphatidylethanol (PEt) was produced in the presence of ethanol. The
      responses of the VSMC from SHR (SHR-cells) to all stimuli were significantly
      greater than those of the VSMC from WKY rats (WKY-cells), which suggests an
      enhanced PLD activity in the SHR-cells. Since PLD is regarded as an enzyme
      involved in signal transduction leading to cell proliferation, this PLD hyper
      reactivity in the SHR-cells may account at least partially for the growth
      abnormality in the SHR-cells.

PMID- 8136773
TI  - Increased urinary dopamine excretion in young patients with essential
      hypertension.
AB  - The evidence that some older patients with essential hypertension have low
      urinary dopamine excretion has brought into question the levels of urinary
      dopamine and plasma dopa, the major source of urinary dopamine, in young patients
      with essential hypertension. Twenty-four-hour urine sodium, creatinine, dopamine
      and noradrenaline and plasma dopa were evaluated in 48 patients with essential
      hypertension aged 18 to 27 years and 25 normotensive subjects. In comparison with
      age-matched normotensive subjects, the hypertensive patients had higher urinary
      dopamine (1920 +/- 80 vs 1520 +/- 130 nmol/day, p < 0.01) and noradrenaline (216
      +/- 11 vs 179 +/- 12 nmol/day, p < 0.05) excretion. There was a significant
      correlation between urinary dopamine and noradrenaline excretion. There was no
      difference in plasma dopa levels between normotensive and hypertensive subjects.
      These results suggest that the elevated conversion of dopa to dopamine in the
      kidney is leading to increased urinary dopamine excretion in young patients with
      essential hypertension.

PMID- 8136774
TI  - Juxtaglomerular cell tumor of the kidney.
AB  - A juxtaglomerular cell tumor (JGCT) was found in a 40 year old woman. For 5 years
      she had mild hypertension, responding to classical anti-hypertensive treatment,
      then she became severely hypertensive. Two renal angiographies and a CT scan were
      reported as normal. A second CT scan and third selective renal angiography were
      diagnostic, associated with lateralization of renin in renal vein measurement.
      Light, electron microscopy and immunohistochemistry of the resected tumor
      confirmed the diagnosis of renin-secreting juxtaglomerular cell tumor of the
      kidney.

PMID- 8136775
TI  - Modulation of circadian rhythm of blood pressure by cortisol in patients with
      hypopituitarism.
AB  - We conducted a study to determine the effect of exogenous cortisol on circadian
      blood pressure changes in patients with hypopituitarism. Under replacement with
      hydrocortisone of 15 to 25mg either once (8:00) or twice a day (8:00 and 20:00),
      and with prednisolone of 3.75 to 5mg once a day, the patients underwent non
      invasive ambulatory blood pressure monitoring for 24 hours. The average 24-hour
      blood pressure before hydrocortisone replacement was 92.9 +/- 1.0 (systolic)/53.2
      +/- 0.8mmHg (diastolic), while that after hydrocortisone replacement once or
      twice a day and prednisolone replacement significantly increased to 108.2 +/-
      1.4/63.5 +/- 0.9mmHg, 109.1 +/- 1.6/62.3 +/- 1.0mmHg, and 105.4 +/- 1.2/62.3 +/-
      0.9mmHg, respectively. Hydrocortisone replacement once a day showed a significant
      increase in day-night differences of blood pressure, while hydrocortisone
      replacement twice a day did not. There were no differences in nocturnal decrease
      in pulse rate between these two replacements. The daytime and nighttime urinary
      excretions of 17-hydroxycorticosteroids in hydrocortisone replacement once a day
      were 7.7mg/12hr (daytime) and 1.4mg/12hr (nighttime), respectively, while those
      in hydrocortisone replacement twice a day were 3.9mg/12hr (daytime) and
      3.6mg/12hr (nighttime), respectively. Urinary 17-ketosteroids, epinephrine and
      norepinephrine did not show any differences between hydrocortisone replacement
      once and twice a day. These results suggest that hydrocortisone administration is
      one of the factors which modulate the circadian variation of blood pressure in
      patients with hypopituitarism, and may also suggest that the circadian change of
      cortisol secretion participates, at least in part, in the formation of an
      intrinsic circadian rhythm of blood pressure.

PMID- 8136776
TI  - Effect of aging on glucose tolerance in spontaneously hypertensive rats.
AB  - We studied the age-related changes of glucose tolerance in female spontaneously
      hypertensive rats (SHR) that did not become obese with aging. Oral glucose
      tolerance test was performed in young (3 months), middle-aged (6 to 11 months),
      and aged (26 months) SHR. Fasting plasma glucose was significantly lower in aged
      SHR than in young SHR. The increase in plasma glucose after glucose
      administration over fasting level was significantly higher in aged SHR than in
      middle-aged SHR, but did not differ between young and aged rats. Pancreatic islet
      size and pancreatic immunoreactive insulin content were similar between young and
      aged SHR. The present study demonstrated that glucose tolerance did not
      deteriorate in SHR with aging, while genetic hypertension persisted. This
      suggests that the persistence of hypertension per se may not affect glucose
      tolerance in SHR.

PMID- 8136777
TI  - Effects of a calcium channel blocker, nicardipine, on pressure-natriuresis in
      Dahl salt-sensitive rats.
AB  - The effects of a calcium channel blocker, nicardipine, on pressure-natriuresis
      responses were studied in Dahl salt sensitive (DS) and resistant (DR) rats.
      Differences in the neural and endocrine background were minimized by renal
      denervation and by holding plasma vasopressin, aldosterone, corticosterone, and
      norepinephrine levels constant by intravenous infusion. The renal plasma flow
      (RPF) and glomerular filtration rate (GFR) of DS rats were disautoregulated in
      the low renal perfusion pressure range, while those of DR rats were
      autoregulated. Administration of nicardipine (0.3 microgram/kg/min) into the
      renal artery significantly increased RPF and GFR and abolished the autoregulation
      in both strains of rats. Nicardipine also sharpened the pressure-natriuresis
      responses in both strains without changes in fractional excretion of sodium.
      These findings suggest that nicardipine increased GFR and thereby improved the
      pressure-natriuresis responses of DS rats.

PMID- 8136778
TI  - Changes in Ca2+ mobilization in platelets from stroke-prone spontaneously
      hypertensive rats.
AB  - Intracellular free Ca2+, [Ca2+]i, levels were measured in platelets from stroke
      prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats
      (WKY) using fura-2AM. In the presence of extracellular Ca2+ (1 mM), [Ca2+]i
      levels in unstimulated platelets of 2- and 9-month-old SHRSP were both
      significantly higher than those of the age matched WKY. In the absence of
      extracellular Ca2+, the levels in platelets from 9-month-old SHRSP were also
      higher than any other groups examined. Receptor-linked Ca2+ influxes of old SHRSP
      were smaller when thrombin or collagen was given to the platelets. Phorbol 12
      myristate 13-acetate (TPA) enhanced more prominently the Ca2+ influx into old
      SHRSP platelets than into old WKY platelets. These results strongly suggest that
      the Ca2+ permeability across plasma membrane is increased in young as well as old
      SHRSP platelets, where the resting [Ca2+]i level is highly sustained because of
      an impaired Ca2+ uptake mechanism and possible enhancement of protein kinase C
      activity.

PMID- 8136779
TI  - Tetanus toxin selectively impairs anti-tumoral but not anti-microbial macrophage
      mediated effector functions.
AB  - The present study was designed to establish the susceptibility of macrophage
      mediated effector functions to tetanus toxin (TT). Using the murine macrophage
      cell line, GG2EE, generated in vitro by v-raf/v-myc oncogenes, we have previously
      provided evidence that TT selectively inhibits interferon gamma (IFN-gamma), but
      not basal, lysozyme activity. Here we show that while neither phagocytic nor
      candidacidal activities are affected by TT treatment, antitumoral activity is
      significantly impaired after exposure to TT. This phenomenon, which is dose
      dependent, is fully ascribed to the holotoxin, as heat inactivated TT, C or A-B
      fragments result ineffective. Furthermore, C but not A-B fragment competes with
      TT in abrogating its inhibitory effects. Overall, these data indicate that TT is
      not a broad-spectrum, down-regulating signal on macrophage-mediated functions,
      thus implying that its toxic action is exerted on specific molecular targets.

PMID- 8136780
TI  - Analysis of some factors involved in the virulence mechanism of Vibrio cholerae
      non-01.
AB  - A study was carried out to evaluate the potential intestinal toxicity of 188
      samples of Vibrio cholerae non-01 isolated from seawater found along the beaches
      of Rio de Janeiro city. Three different assays were carried out involving: (a)
      detection of vascular permeability factor (PF) in guinea pigs (together with
      assessment of two culture media for production of the toxin); (b) intestinal
      fluid accumulation (FA) in suckling mice; and (c) detection of haemolysin. The
      results demonstrated that both culture media gave a similar level of performance.
      In the animal assays, 43% of the samples induced PF in guinea pigs, 28.7% caused
      intestinal fluid accumulation in suckling mice, and 63.28% contained haemolysin.
      Only 4.25% of the samples gave positive results in all three tests.

PMID- 8136781
TI  - Comparison of dimethyl dioctadecyl ammonium bromide, Freund's complete adjuvant
      and mineral oil for induction of humoral antibodies, cellular immunity and
      resistance to Newcastle disease virus in chickens.
AB  - Dimethyl dioctadecyl ammonium bromide (DDA), a lipophilic quaternary amine, was
      evaluated in adult chickens for potentiation of immunological responses to
      subcutaneously administered inactivated Newcastle disease virus (NDV) vaccines.
      DDA enhanced humoral and cell-mediated immune (CMI) responses to levels which
      were significantly higher than those induced by the vaccine alone The
      haemagglutination inhibition antibody titers induced by DDA were slightly lower
      than those induced by mineral oil although neutralizing antibody titers seemed to
      be higher. DDA induced strong CMI (DTH and lymphocyte proliferation) responses,
      more than those induced by Freund's complete adjuvant and mineral oil. Both DDA
      and mineral oil induced comparable high levels of protection to challenge doses
      of 200,000 LD50 per chicken. No toxic effects or local tissue damage were
      observed in any of the inoculated chickens.

PMID- 8136782
TI  - The effects of 3-hydroxybutyrate and glucose on human T cell responses to Candida
      albicans.
AB  - Diabetic patients are particularly susceptible to mucocutaneous candidosis. T
      lymphocytes are central to the induction of antigen-specific immune responses and
      may be sensitive to the biochemical abnormalities associated with poorly
      controlled diabetes; namely, hyperglycaemia and/or ketonemia. To examine this we
      have studied the effect of varying concentrations of glucose and 3
      hydroxybutyrate (3-HB) in cultures of human T cells stimulated with Candida
      albicans antigen. Proliferation of T cells from six type 1 diabetic and six non
      diabetic control subjects was significantly inhibited (both P < 0.05) in glucose
      free medium, and at a glucose concentration of 80 mmol l-1 as compared with
      cultures containing glucose at physiological concentration (5 mmol l-1). 16 and
      32 mmol l-1 3-HB also inhibited T cell proliferation in the presence of 5 mmol l
      1 glucose (P < 0.05). The effect of glucose and 3-HB were not additive and the
      inhibition was not due to cell death. 32 mmol l-1 3-HB had less effect when
      present solely during antigen pulsing than during subsequent lymphocyte
      stimulation, and was effective even when added after 72 h of a six day culture.
      This suggests that ketosis affects T cell proliferation more than antigen
      processing and presentation. We conclude that human antigen-specific T cell
      proliferation is inhibited in vitro only by concentrations of 3-HB encountered in
      moderately severe diabetic ketoacidosis, and by glucose concentrations found in
      severe hyperosmolar non-ketotic coma. The impairment of T cell function under
      such extreme conditions could be implicated in the close association of diabetic
      ketoacidosis with deep fungal infections, particularly invasive mucormycosis.

PMID- 8136783
TI  - Campylobacter jejuni: specific oligonucleotides and DNA probes for use in
      polymerase chain reaction-based diagnosis.
AB  - A 1189 base-pair long DNA fragment, VS1, was isolated from a Campylobacter jejuni
      CIP 70.2 cosmid library and was found to contain regions specific for this
      bacterial species. For detection and identification of C. jejuni, two
      oligonucleotides derived from the VS1 sequence were used as primers in polymerase
      chain reaction tests on genomic DNAs from 38 campylobacter and from 10 non
      Campylobacter strains. A specific, 358 base-pair long DNA fragment was amplified
      only when C. jejuni DNA was used as a target. The detection limit of the
      amplification reaction was as low as 1.86 fg DNA, which is the equivalent of one
      C. jejuni genome.

PMID- 8136784
TI  - Immunosuppression induced by Salmonella involves inhibition of tyrosine
      phosphorylation in murine T lymphocytes.
AB  - It is well known that facultative intracellular pathogens such as Salmonella
      suppress the host immune system. In the present study we attempted to clarify the
      mechanism responsible for the suppression of T-cell proliferation in mice
      infected with Salmonella typhimurium. The proliferation of murine spleen cells
      stimulated with a T-cell mitogen such as phytohemagglutinin (PHA) or concanavalin
      A (ConA) was significantly suppressed when the mice were infected with S.
      typhimurium, but not with Escherichia coli. The suppression of T-cell
      proliferation did not necessarily parallel the level of interleukin-2 (IL-2)
      secretion, and was not restored by treatment with a calcium ionophore,
      indomethacin or IL-2. Only phorbol 12-myristate-13 acetate (PMA), an activator of
      protein kinase C (PKC), caused a slight recovery of cell proliferation with an
      augmentation of IL-2 secretion. Furthermore, Western blotting using anti
      phosphotyrosine antibodies showed that the mitogen-induced tyrosine
      phosphorylation of 120-, 106-, 94-, 76-, 68- and 57-kDa proteins in murine
      splenic T-cells was inhibited by S. typhimurium infection. Also, the inhibition
      of tyrosine phosphorylation was not restored by treatment with PMA. These results
      suggest that the suppression of T-cell proliferation induced by Salmonella
      infection may be regulated by inhibition of tyrosine phosphorylation in T-cells,
      although the inhibition is not associated with PKC activation and subsequent IL-2
      secretion of T cells.

PMID- 8136785
TI  - Synaptic vesicle life cycle and synaptic turnover.
AB  - Cholinergic synaptic vesicles contain a mixture of soluble low molecular mass
      constituents. Besides acetylcholine these include Ca2+, ATP, GTP, small amounts
      of ADP and AMP, and also the diadenosine polyphosphates Ap4A and Ap5A. In
      synaptic vesicles isolated from the electric ray these diadenosine polyphosphates
      occur in mmol concentrations and might represent a novel cotransmitter. The
      membrane proteins of cholinergic synaptic vesicles presumably are identical to
      those in other types of electron-lucent synaptic vesicles. A presumptive
      exception are the transmitter-specific carriers. The life cycle of the synaptic
      vesicle in intact neurons and in situ was investigated by analysis of all
      cytoplasmic membrane compartments that share membrane integral proteins with
      synaptic vesicles. The results suggest that the synaptic vesicle membrane
      compartment might originate from the trans-Golgi network and, after cycles of exo
      and endocytosis in the nerve terminal, might fuse into an endosomal membrane
      compartment early on retrograde transport. Tracer experiments using membrane
      proteins and soluble contents suggest that the synaptic vesicle membrane
      compartment does not intermix with the presynaptic plasma membrane on repeated
      cycles of exo- and endocytosis if low frequency stimulation is applied. A cDNA
      has been isolated from the electric ray electric lobe that codes for o-rab3, a
      small GTP-binding protein highly homologous to mammalian rab3. While abundant in
      the nerve terminals of the electric organ and at the neuromuscular junction this
      protein occurs only in limited subpopulations of nerve terminals in electric ray
      brain. Immunocytochemical analysis using the colloidal gold technique and a
      monospecific antibody against o-rab3 suggests that the GTP-binding protein
      remains attached to recycling synaptic vesicles. No evidence was found for a
      major contribution of an intraterminal endosomal sorting compartment involved in
      synaptic vesicle recycling.

PMID- 8136786
TI  - Two independently regulated secretory pathways in mast cells.
AB  - We review here evidence that mast cells independently secrete large and small
      vesicles. Release of small vesicles is triggered by Ca2+. Combining capacitance
      measurements and flash photolysis of caged Ca2+, we demonstrate Ca-triggered
      exocytosis that is kinetically identical to the release of dense-core peptidergic
      vesicles from pituitary melanotrophs. It is suggested that the secretory pathway
      used for hormone secretion in neuroendocrine cells is also active in mast cells
      and eosinophils. The nature of the mediator thus secreted is unknown.

PMID- 8136787
TI  - Evidence against the swelling hypothesis for initiation of exocytosis in
      terminals of chromaffin cell processes.
AB  - Exocytosis of transmitter-containing granules was directly visualized in neurite
      terminals of cultured chromaffin cells under a video-enhanced contrast
      microscope. The granule diameter did not change immediately before their
      exocytotic responses. Large granules responded as early as small ones. These
      findings are inconsistent with the swelling hypothesis for initiation of
      exocytosis.

PMID- 8136788
TI  - Role of psychosomatic factors in peptic ulcer disease.
AB  - Evidence indicates that a link between peptic ulcer disease (PUD) and selected
      psychosomatic factors may exist. A series of 70 consecutive male and female adult
      patients were categorized by peptic symptoms and divided into four groups: a)
      controls; b) gastric ulcer (GU); c) duodenal ulcer (DU); and d) chronic non-ulcer
      dyspepsia (CNUD). All patients were interviewed and asked to answer a
      questionnaire that included demographics, medical history and the incidence of
      negative life events. A decreased level of activity was a predominant finding in
      GU, DU and CNUD patients. Family history of PUD may be correlated with CNUD. Of
      interest was the finding that DU and CNUD patients presented a higher incidence
      of negative life events when compared to the other study groups. Negative life
      events that produce considerable stress may predispose to peptic symptoms in
      certain patients.

PMID- 8136789
TI  - Depressive behavior and stress ulcer in Wistar Kyoto rats.
AB  - Wistar Kyoto (WKY) rats, as compared to several other rat strains, are hypoactive
      in the open field test and in the defensive burying test. WKY rats readily
      acquire a learned helplessness task as well as a passive avoidance tasks. WKY
      rats also reveal a greater susceptibility to restraint-induced stress ulcer. The
      behavioral tests suggest the presence of depressive behavior in WKY rats. When
      exposed to the Porsolt forced-swim test of 'behavioral despair', WKY rats are
      judged as exhibiting more depressive behavior. Desipramine not only reduced
      immobility in the forced-swim test, but also diminished the severity of restraint
      induced stress ulcer. These data suggested a heightened activity of the
      hypothalamic-pituitary axis. Basal plasma ACTH levels did not differ between WKY
      rats and Wistar rats, but serial plasma ACTH response to restraint stress was
      significantly greater for WKY rats. These data suggest that depressive behavior
      is a characteristic of WKY rats and this strain is a valuable model for studying
      depression which may be induced by an exaggerated stress response.

PMID- 8136790
TI  - Effects of preadaptation to restricted feeding and cimetidine treatment on
      gastric mucosal injury and wheel running during exposure to activity-stress.
AB  - The relationship between gastric injury and wheel running was examined during an
      activity-stress (A-S) experiment. In Experiment 1, rats were preadapted to a 1-h
      restricted feeding schedule for either 0, 15, 25 or 35 days prior to entering
      activity wheels. All rats preadapted to the 1-h feeding schedule had
      significantly less gastric damage than rats without any preadaptation experience.
      Survival of A-S was related to the length of preadaptation experience. Regardless
      of preadaptation experience, rats increased daily running with the greatest
      increase occurring during the 6-h period preceding the feeding hour. In
      Experiment 2, rats were injected twice daily with cimetidine (100 mg, ip) or
      vehicle during the 6-h preceding the feeding session. Rats treated with
      cimetidine had less mucosal injury but had no increased survival when compared to
      rats injected with the vehicle. Cimetidine treated rats had essentially the same
      running pattern as controls. These results demonstrated that the process of
      mucosal injury did not stimulate excessive wheel running. The data also suggest
      that mucosal injury is not related to survival in A-S rats.

PMID- 8136791
TI  - Parallelism among stress effects on ulcer, immunosuppression and analgesia:
      commonality of mechanisms?
AB  - Some general principles and mechanisms have been discovered that govern proactive
      effects of one stress on animals' later stress or challenge induced behavior,
      nociception, immune function, and stomach ulcerations. As described below, these
      principles demonstrate a considerable degree of parallelism across the domains
      represented by measures of learning deficits and fear-related behaviors,
      hypoalgesia, immunological status and stress gastric ulcerations. At a minimum,
      these parallels suggest that operational factors found important in one domain
      are likely factors of importance in the other domains. Beyond this, these
      parallels are permissive of an inference of commonality in underlying processes.
      Nonetheless, results reviewed below suggest that the specific response of the
      organism to stress is highly dependent on specific characteristics of the
      stressor.

PMID- 8136792
TI  - Effects of oxytocin on emotional stress and stress-induced gastric lesions.
AB  - The effect of oxytocin has been studied in gastric lesions induced by cold-plus
      restraint stress or by subcutaneous (sc) administration of cysteamine.
      Intracerebroventricular (icv) injection of the peptide was followed by a
      reduction of the incidence of gastric lesions in both experimental models. This
      effect was comparable to that found after icv injection of prolactin, a peptide
      which is known to facilitate adaptation to stress and reduce the incidence of
      stress-induced gastric lesions. These results may be relevant in focusing on the
      general role of oxytocin as a protective factor against stress-induced biological
      modifications.

PMID- 8136793
TI  - CNS effects on gastric functions: from clinical observations to peptidergic brain
      gut interactions.
AB  - Clinical observations as early as the last century pointed to the stomach's link
      to the brain. Animal studies in this century have given us detailed information
      about the neuroanatomical and neurophysiological basis of brain-gut interactions.
      Psychological stress models and stereotaxic brain procedures have been important
      tools in gaining this information. During the last 10 years, there has been much
      focus on the effects of neuropeptides on gastric functions. Several CNS-peptides
      have indeed been shown to influence multiple gastric functions such as: acid
      secretion, bicarbonate secretion, mucus secretion, motility, blood flow and
      prostaglandin synthesis. Accordingly, direct CNS-application of these peptides
      also influences the development of gastric erosions during experimental stress
      procedures.

PMID- 8136794
TI  - Enterostatin: a gut-brain peptide regulating fat intake in rat.
AB  - The effect of enterostatin on high-fat food intake has been investigated. After
      18 h of food deprivation, rats were injected intravenously with enterostatin
      (VPGPR). A dose of 38 nmol of enterostatin gave a significant inhibition of high
      fat food intake, while at a higher dose of 76 nmol the inhibiting effect was
      lost. During the first hour, after injection of enterostatin, there was even a
      slight increase in food intake. Binding studies of tritiated enterostatin to
      crude brain membranes indicated one binding site with high affinity (Kd = 0.5 nM)
      and one with low affinity (Kd = 170 nM). The two dissociation constants suggest
      different receptor subtypes and could explain why enterostatin both can inhibit
      and, at high doses, stimulate fat intake in rats.

PMID- 8136795
TI  - Involvement of calcitonin gene-related peptide in rat experimental colitis.
AB  - This study investigated the role of capsaicin-sensitive fibers on
      trinitrobenzensulphonic acid (TNB)-induced colitis in rats. Capsaicin
      pretreatment (164 + 164 mumol/kg sc in 2 days) produced an increase of damaged
      area and colon wet weight at 24 h and 1 week after the challenge. On the other
      hand, acute stimulation of sensory nerves by local application of capsaicin (1.2
      60 mumol/kg) as well as exogenous administration of CGRP (2.6-26.3 nmol/kg sc)
      ameliorated the lesions and reduced the increase of colon weight in TNB-colitis.
      The protective effect of acute capsaicin (7.7 mumol/kg) was transient and lost in
      capsaicin-desensitized animals, showing its specificity and the likely
      participation of acute release of peptides in this mechanism. Moreover,
      development of TNB colitis was associated with a selective decrease in tissue
      CGRP-like immunoreactivity. These findings provide evidence that capsaicin
      sensitive nerves, probably via the release of protective neurotransmitters such
      as CGRP, play a defensive role in colitis.

PMID- 8136796
TI  - A validation study of the domains of the core EORTC quality of life
      questionnaire.
AB  - A cohort study was conducted to investigate the construct validity of the domains
      of the EORTC QLQ-C30 (European Organization for the Research and Treatment of
      Cancer Quality of Life Questionnaire). Ninety-six patients undergoing
      chemotherapy at the Kingston Regional Cancer Centre, Kingston, Canada were given
      the EORTC QLQ-C30 and two out of four comparison scales; the Sickness Impact
      Profile, the McGill Pain Questionnaire, the General Health Questionnaire and the
      Cancer Rehabilitation Evaluation System, to complete during their clinic visits.
      Using the multitrait-multimethod matrix to examine relationships, the Spearman
      ranked correlation coefficients of similar and dissimilar domains between the
      EORTC QLQ-C30 and the comparison scales were compared. The EORTC QLQ-C30 domains
      of pain and physical and role functioning performed well in that they converged
      and diverged appropriately with the other instruments. The domain of
      psychological functioning had strong associations with domains thought to be
      dissimilar (social interaction and fatigue). Social interaction and financial
      impact diverged across dissimilar domains. This lack of specificity may relate to
      question wording. The symptom domain had strong associations with other domains
      across the comparison scales. This study shows that the domains of the EORTC QLQ
      C30 have substantial construct validity in the multidimensional assessment of the
      quality of life of cancer patients and identifies where further work is required.

PMID- 8136797
TI  - Convergent validation of quality of life assessments for persons with severe
      mental illnesses.
AB  - The impact of interventions on the quality of life (QOL) experienced by persons
      with severe and persistent mental illnesses (SPMI) has attracted considerable
      political, clinical and research attention over the past decade, and continues to
      do so. This study examines the convergent validity of two commonly used QOL
      measures for this group of patients, the Lehman Quality of Life Interview and the
      Heinrichs-Carpenter Quality of Life Scale, computing the correlations between
      comparable constructs from the two measures administered at the same time and 2
      months apart. Correlations were positive and significant although low to moderate
      in magnitude. Considering the considerable differences in the methods of
      assessment employed by the two measures, the lack of precise congruence between
      their constructs, and the 2-month time interval, these findings support their
      convergent validity. Various conceptual issues regarding the validity and
      interpretation of QOL assessments for persons with SPMI are discussed.

PMID- 8136798
TI  - Quality of life of alcoholics and non-alcoholics: does excessive drinking make a
      difference in the urban setting?
AB  - The current study assessed whether perceived quality of life differed between
      alcoholics and non-alcoholics. Patients attending an urban-based hospital were
      screened for alcoholism using the CAGE questionnaire. Patients were recruited
      from an out-patient clinic setting as well as from an in-patient substance abuse
      unit. Quality of life scores were based on Chubon's (1987) Life Situation Survey.
      Results indicated that alcoholics experience a lower quality of life than their
      non-alcoholic counterparts regardless of setting; however, all patients reported
      experiencing poor life quality. The impact of alcoholism treatment programmes on
      patients already experiencing low quality of life is questioned.

PMID- 8136800
TI  - Swedish population norms for the GHRI, HI and STAI-state.
AB  - This paper presents reference values for two questionnaires measuring general
      health, the General Health Rating Index (GHRI) and the Health Index (HI) and one
      questionnaire measuring anxiety state, the State Trait Anxiety Inventory (STAI
      state). The sample used was randomly selected from a Swedish urban population
      consisting of 180 individuals (90 men, 90 women), divided into three age groups,
      26-45, 46-65 and > 65 years. There was a main effect for age on the total GHRI
      score. The GHRI score was lower for older than for younger people, which is in
      agreement with earlier studies. For the HI there were main effects both for
      gender and age and no interaction was found. Although the sample size is small
      our result was in agreement to earlier studies and to health statistics in Sweden
      1989. The health measures significantly correlated with the scores of anxiety
      inventory used. The total GHRI scores correlated positively and significantly
      with the HI scale (r = 0.7, p < 0.001). The GHRI and HI scales correlated
      negatively and significantly with the STAI scale (r = -0.4, p < 0.001, r = -0.4,
      p < 0.001) respectively. Thus, the better the general health the lower the rated
      anxiety. The value of health status measures in clinical research is reasonably
      well established, but their values for clinical care are less clear. The use for
      health index scores for quality assurance purpose is almost unexplored and could
      possibly be used for outcome measures in evaluating areas of nursing
      interventions. The short Health Index is one possible outcome measure.

PMID- 8136799
TI  - Quality of life of persons with onychomycosis.
AB  - Onychomycosis is a fungal infection of the nails which, although unsightly in
      appearance, is often considered to be a cosmetic problem. This research reports
      on the development and performance of a quality-of-life instrument to measure the
      impact of this disease on the patients' mental and general health, social
      functioning, pain, and self-confidence. In telephone interviews, 680 members of a
      health maintenance organization (299 with onychomycosis and 381 without) were
      asked a battery of items regarding quality of life (mental and social
      functioning, self-esteem, pain) and specific problems and symptoms related with
      one's nails. Persons with onychomycosis had significantly poorer ratings compared
      with the healthy persons with respect to general health (p = 0.02) and bodily
      pain p < 0.001). Persons with onychomycosis also had significantly (p < 0.05)
      poorer ratings for mental health, social functioning, health concern, physical
      appearance, and functional limitations associated with activities involving
      standing on one's feet or working with one's fingers. This study is the first to
      document the impact of onychomycosis on an individual's quality of life. Persons
      with onychomycosis may adapt to this condition, but they continue to experience
      embarrassment and discomfort that reduces their quality of life.

PMID- 8136801
TI  - The importance of quality of life research for health care reform in the USA and
      the future of public health.
AB  - Quality of life research data have significant implications for the social and
      public policy in the USA as it can be used to evaluate the cost-effectiveness of
      various permutations of treatment as well as the 'human effectiveness' of health
      care system restructuring. The USA spends more on health care per capita than any
      other industrialized nation, yet on major health indicators, such as infant
      mortality rate, this expenditure is not related to beneficial effects on the
      community. When epidemiological and quality of life data drive national health
      care planning, improved approaches to the management of health service delivery
      may become apparent. Ultimately only the patient or consumer can determine if a
      particular treatment is successful; the same may be true for health care reform.

PMID- 8136802
TI  - [Articular and vertebral tuberculosis].

PMID- 8136803
TI  - [Anti-inflammatory properties of interleukin-4].
AB  - Interleukin 4 (IL4) is a cytokine produced by T cells and mast cells/basophils.
      IL4 has a key role in IgE production and in the pathogenesis of atopic diseases.
      Disorders such as rheumatoid arthritis are characterized by increased production
      of proinflammatory cytokines and reduced production of IL4. Furthermore,
      rheumatoid T cells are of the TH 1 type, not producing IL4. In contrast,
      circulating IL4 has been detected in scleroderma patients, whose T cells are of
      the TH 2 type, producing IL4. Since IL4 inhibits the production of
      proinflammatory cytokines such as IL1, IL6, TNF alpha and IL8, we hypothesized
      that a deficit in IL4 production might be related to the pathogenesis of
      rheumatoid arthritis. Addition of IL4 strongly reduced the production of
      proinflammatory cytokines and expression of corresponding mRNA by synovial
      membrane pieces from RA patients. RA synovitis is also associated with marked
      proliferation of synoviocytes. Studies of synoviocytes showed that IL4 inhibited
      the growth promoting effect of PDGF and IL1 beta. IL4 also inhibited production
      of IL6 by juxta-articular bone pieces. IL4 was found to reduce disease activity
      and progression in various arthritis models. These anti-inflammatory and anti
      proliferative properties suggest that IL4 may be of potential clinical value in
      RA. Conversely, as IL4 induces dermal fibroblasts to secrete collagen, IL4 might
      be involved in the pathogenesis of scleroderma.

PMID- 8136804
TI  - [Treatment of refractory rheumatoid polyarthritis by extracorporeal
      photochemotherapy].
AB  - Extracorporeal photochemotherapy (EPC) has been used to treat cutaneous T-cell
      lymphomas as well as a number of immune-mediated disorders. Seven patients above
      50 years of age with refractory rheumatoid arthritis (RA) were treated by EPC.
      Mononuclear cells were harvested, exposed to ultraviolet A light in the presence
      of 8-methoxypsoralen, then reinfused into the patient. This procedure was
      repeated eight times over a three-week period. Improvements in clinical
      parameters were seen in every case as early as the second week and persisted
      throughout the duration of EPC. Improvements for more than three months were
      observed in two patients. C-reactive protein levels declined during the treatment
      period. No adverse reactions were recorded. The mechanism of action of EPC in RA
      requires elucidation and a controlled study is needed to confirm the efficacy of
      this technique.

PMID- 8136805
TI  - [Infantile scleroderma. Apropos of 11 cases].
AB  - Scleroderma is uncommon in children and adolescents. Eighty-four cases have been
      reported. With reference to a new series of 11 cases, the clinical features and
      course of the disease are described. Prognosis was good. There have been no
      deaths and none of the patients have significant visceral organ damage.

PMID- 8136806
TI  - [Measurement of the hip joint space using automatic digital image analysis].
AB  - Joint surface area (JSA) and mean joint space width (MJSW) at the hip were
      measured using a ICMS-Techline computer program to analyze digitalised frontal
      weight-bearing roentgenograms of the pelvis. With this technique, the portion of
      joint space studied is always the same in a given patient and is enclosed within
      an acute ECS angle whose apex C is the center of the head of the femur and whose
      ends E and S are the lateral rim of the acetabulum and the highest point of the
      homolateral sacral wing respectively. ECS varies across individuals but remains
      constant in a given hip. Twenty hips were included in the first part of the
      study. For each hip, three roentgenograms were taken at five-minute intervals by
      three different radiologists who used their own constants (settings, position of
      the subject). JSA and MJSW are determined five times on each film by two
      different observers who had no information on the films under study. The
      interobserver coefficient of variation (CV) was 4.7% for JSA and 3.3% for MJSW.
      Intra-observer CVs were 2.97 and 3.54% for MJSW and 4.32% and 5.13% for JSA.
      There was a very close correlation between MJSW and JSA (r = 0.87, p < 0.0001).
      MJSW was then determined for roentgenograms of 30 hips with osteoarthritis.
      Results were compared with the values obtained using Lequesne's method of joint
      space measurement at the site of maximum narrowing. Measurements were performed
      in a double-blind fashion by two observers. The correlation coefficient was r =
      0.89 (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136807
TI  - [Socioeconomic incidences and prognostic factors of low back pain caused by
      occupational injuries among the hospital personnel of Grenoble University
      Hospital Center].
AB  - Low back pain is generally believed to be common among hospital employees. This
      cross-sectional, retrospective study was carried out to determine the annual
      incidence of low back pain ascribable to occupational injuries in hospital
      employees and to evaluate factors influencing the prognosis of these injuries. In
      1989, 70 employees working at the Grenoble Teaching Hospital (GTH) reported an
      occupational injury responsible for low back pain. Each of these employees filled
      out an epidemiological questionnaire during a routine evaluation by a
      rheumatologist. Overall annual incidence of occupational injuries with subsequent
      low back pain was 1.9% among GTH employees. Higher incidences were seen among
      employees whose occupations involved patient transfer, as well as among nursing
      assistants. Activities associated with an increased risk of low back pain
      included handling of patients or objects and work requiring prolonged periods in
      uncomfortable positions or in the standing position. A previous history of low
      back disease and a longer period of time in the current work were also associated
      with an increased risk of low back pain. Characteristic clinical profiles of
      patients with low back pain subsequent to occupational injury were determined by
      occupation and type of hospital department. The analysis of long-duration absence
      from work and long-term consequences on career confirmed the significant adverse
      socioeconomic impact of these injuries.

PMID- 8136808
TI  - [Systemic manifestations after breast prosthesis].
AB  - Are breast implants associated with systemic manifestations? Because reliable,
      systematic evaluations of effects potentially associated with silicone implants
      are lacking, the safety of breast implants generates endless, much publicized
      controversies. In this update, we review published reports of systemic
      manifestations after mammoplasty, effects of implant removal, pathological
      findings, and experimental properties of silicones. Results of our analysis
      suggest that breast implants have a potential for inducing connective tissue
      disease in some individuals. Follow-ups of patients enrolled in prospective
      studies are still too short to allow definite conclusions.

PMID- 8136809
TI  - [Camptocormia in the elderly patient: myopathy or muscular dystonia?].
AB  - Two cases of camptocormia in elderly patients are reported. Both patients
      presented with an anterior curvature of the trunk which disappeared in the
      decubitus position. Computed tomography demonstrated hypodensity of the muscles
      which preceded atrophy. Histological changes were of low specificity and diverse
      with irregular and a trophic muscle fibers and occasionally endomysial fat or
      mitochondrial abnormalities. These findings suggest that camptocormia may be the
      consequence of a disease of spinal muscles. Pathophysiological hypotheses include
      neurogenic atrophy of spinal muscles, spinal amyotrophy, and delayed primary
      myopathy. None of these hypotheses was consistent with findings in our two
      patients. The terms "muscular dystrophy" and "mitochondrial myopathy"
      occasionally used seem inappropriate in view of the lack of specificity of the
      lesions. A better term may be "muscular insufficiency", the mechanism of which is
      still unclear.

PMID- 8136811
TI  - [Disclosing muscular metastases. Their peculiarities apropos of 3 cases].
AB  - Three cases of muscular metastasis as the first manifestation of malignancy are
      reported. These patients had no previous history of malignancy. All three were
      male. One had a single metastasis in the gluteus minimus muscle, and the other
      two had multiple metastases which were located in the adductor compartment of the
      thigh in one case and in the biceps brachii, quadriceps femori, and paraspinal
      muscles in the other. These metastases first manifested as a painful mass. The
      various imaging techniques (ultrasonography, computed tomography, and magnetic
      resonance imaging) determined the location and extension of the masses, although
      the images were nonspecific. The metastatic nature of the tumors was confirmed
      only upon histological studies. With reference to these three cases, features of
      muscular metastases are reviewed. The development of muscular metastases is an
      infrequent occurrence during the course of a cancer. The mechanisms which may
      explain the low incidence of muscular metastases are discussed.

PMID- 8136812
TI  - [Metastases in the cauda equina in visceral cancers. Apropos of 2 cases].
AB  - Two new cases of cauda equina metastases from visceral cancers are reported. This
      diagnosis is only infrequently considered in patients with intra-dural lesions
      visualized by magnetic resonance imaging or saccoradiculography. The diagnosis is
      especially difficult in patients with no known primary cancer. Diagnosis rests on
      surgery during which only a biopsy is performed. Treatment is symptomatic and
      focuses on relieving pain. Prognosis is bleak.

PMID- 8136810
TI  - [Polyarthritis in 4 patients treated with intravesical BCG-therapy for carcinoma
      of the bladder].
AB  - Intravesical administration of Calmette-Guerin bacillus (BCG) is effective in the
      treatment of superficial bladder carcinoma. Transient arthritis or migratory
      arthralgia has been reported in 0.5% of cases. The authors report on four men
      (mean age 65 years), who developed an oligoarthritis in three cases after the
      2nd, 5th, and 6th weekly instillation of Pasteur BCG, respectively, and
      symmetrical polyarthritis in one after 48 BCG instillations over a three-year
      period. Joints involved were the knees (3/4), ankles (3/4), shoulders (1/4),
      wrists, and hands (1/4). Features included morning stiffness and local evidence
      of inflammation. All four patients had an elevated erythrocyte sedimentation rate
      and negative tests for rheumatoid factor. Neutrophils were the main cell type in
      synovial fluid. Synovial biopsy performed in two cases revealed non-specific
      inflammation. Erosions of the metatarsophalangeal joints were observed in one
      patient. Locoregional or systemic symptoms included transient fever (3/4),
      cystitis (4/4), urethritis (1/4), epididymoorchitis (2/4), conjunctivitis (1/4),
      and pleural effusion with pericarditis (1/4). The BCG was recovered from an
      epididymal specimen in one patient. Two patients were positive for the HLA B27
      antigen. Outcome was favorable in every case (range: 15 days-6 months) after
      discontinuation of BCG therapy and administration of isoniazid, rifampin, and
      prednisone (3 patients) or NSAID (1 patient). Various pathogenic hypotheses for
      BCG-induced arthritis are discussed, including infection, immune responses to
      heat shock proteins, and reactive arthritis.

PMID- 8136813
TI  - [Sciatica caused by an intraspinal synovial cyst with erosion of the posterior
      arch].

PMID- 8136814
TI  - [Massive calcinosis of a spinal synovial cyst after intra-articular injection of
      long-acting corticosteroid].

PMID- 8136815
TI  - [Diffuse polycystic bone hemangiomatosis].

PMID- 8136816
TI  - Cytokines and the acute phase response in SLE.

PMID- 8136817
TI  - Hormonal aspects of lupus: therapeutic possibilities.

PMID- 8136818
TI  - Hydroxychloroquine, dosage parameters and retinopathy.
AB  - In a study designed to determine the presence of retinopathy in patients taking
      hydroxychloroquine we compared 82 patients attending a rheumatology clinic who
      had taken hydroxychloroquine for over 1 year with controls. Outcome measurements
      included fundoscopy, fundus photography and automated computerized visual fields
      of the macular area. No patient was found to have retinopathy. No correlation
      could be found between indices of visual field function and total drug usage,
      average daily dose, dosage in mg/kg body weight or duration of treatment.
      Retinopathy is unlikely to occur at dosages of hydroxychloroquine of less than
      6.5 mg/kg body weight with under 10 years of treatment. Present guidelines for
      ophthalmic screening of patients on antimalarial therapy are too rigorous and
      visual field testing if not of benefit. Further recommendations are made for
      ophthalmic supervision.

PMID- 8136819
TI  - Pulmonary arterial hypertension responsive to immunosuppressive therapy in
      systemic lupus erythematosus.
AB  - Two female patients with recent diagnosis of systemic lupus erythematosus (SLE)
      are reported. Pulmonary arterial hypertension was diagnosed by Doppler
      echocardiography. Immunosuppressive therapy was started at the time of diagnosis
      of SLE. After 2 months of therapy, Doppler echocardiography was repeated and the
      estimated pulmonary artery systolic pressure was substantially decreased from 78
      to 42 mmHg and from 67 to 42 mmHg, respectively, along with significant
      improvement of the clinical conditions.

PMID- 8136820
TI  - In vitro modulation of anti-DNA secreting peripheral blood mononuclear cells of
      lupus patients by anti-idiotypic antibody of pooled human intravenous immune
      globulin.
AB  - Anti-idiotypic antibody and its F(ab')2 fragments prepared from pooled normal
      human IgG had a partial inhibitory effect on the spontaneous in vitro secretion
      of anti-DNA antibodies from blood mononuclear cells of lupus patients. The
      inhibitory effect was specific for anti-DNA secretion as the anti-idiotype failed
      to inhibit the spontaneous secretion of anti-tetanus toxoid in the same culture
      supernatants. Non-anti-DNA IgG or its F(ab')2 fragments from pooled normal human
      IgG had less inhibitory effect on anti-DNA secretion than the purified anti-Id.
      In vitro polyclonal IgG secretion by lupus blood mononuclear cells was equally
      inhibited by both the anti-idiotype and the non-anti-DNA IgG of pooled normal
      human IgG. There was no correlation between the in vitro suppression of anti-DNA
      and that of total IgG or of anti-tetanus toxoid antibody. Pooled normal human IgG
      could have a potential beneficial effect in the therapy of systemic lupus
      erythematosus by inhibiting anti-DNA production via an anti-idiotypic mechanism.

PMID- 8136822
TI  - Oestrogens, bones and systemic lupus erythematosus.

PMID- 8136821
TI  - Malignancy in systemic lupus erythematosus: a report of five cases in a series of
      96 patients.
AB  - The association of systemic lupus erythematosus (SLE) and malignancy has been
      reported previously and suggests an increased risk of cancer in this disease.
      Lymphomas are the most frequent neoplasias reported in these patients and
      carcinoma of the cervix and breast are also seen. Several factors probably play a
      role in the aetiology of malignancies associated with SLE including intrinsic
      disturbances of immunity and concomitant immunosuppressive therapy. We report
      five solid tumors (one breast carcinoma, one squamous cell carcinoma of the anus,
      one adenocarcinoma of the rectum, one carcinoma of the cervix and one carcinoma
      of the gallbladder) among 96 patients with SLE. The most striking finding in this
      study was the absence of haematological malignancies. The incidence of malignancy
      in the series, the age of diagnosis of SLE and neoplasia and the time delay
      between SLE and malignancy diagnosis was similar to other series. We did not find
      any clinical or immunological feature that predicted the development of
      neoplasia. In conclusion, patients with SLE may have the same malignancies as the
      general population after adjustment for age and sex. There are no predictive
      indicators for malignancy and immunosuppressive therapy may be a contributing
      factor.

PMID- 8136823
TI  - Bullous systemic lupus erythematosus--a variable disease.
AB  - We describe a patient with the rare diagnosis of 'Bullous Systemic Lupus
      Erythematosus'. She is unusual in presenting with classical dermatitis
      herpetiformis, before the emergence of systemic features. In addition, on
      indirect immunofluorescence on sodium chloride split skin, there was epidermal
      binding. Immunoblotting was negative for type VII collagen.

PMID- 8136824
TI  - Effect of aminoglutethemide on the activity of a case of a connective tissue
      disorder with features of systemic lupus erythematosus.

PMID- 8136825
TI  - PEPing up preimplantation testing.

PMID- 8136826
TI  - Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG
      trinucleotide on chromosome 12p.
AB  - Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant
      neurodegenerative disorder characterized by combined systemic degeneration of the
      dentatofugal and pallidofugal pathways. We investigated a candidate gene and
      found that DRPLA patients had an expanded CAG trinucleotide repeat in a gene on
      the short arm of chromosome 12. The repeat size varied from 7-23 in normal
      individuals. In patients one allele was expanded to between 49-75 repeats or
      occasionally even more. Expansion was usually associated with paternal
      transmission and only occasionally with maternal transmission. Repeat size showed
      a close correlation with age of onset of symptoms and disease severity. We
      conclude that DRPLA is the seventh genetic disorder known to be associated with
      expansion of an unstable trinucleotide repeat.

PMID- 8136827
TI  - Preimplantation single cell analyses of dystrophin gene deletions using whole
      genome amplification.
AB  - Primer extension preamplification (PEP) increases the scope and capacity of
      single cell genetic diagnosis by generating sufficient template to perform
      multiple subsequent DNA analyses using the polymerase chain reaction. We report
      the simultaneous analysis of single cells at five commonly deleted dystrophin
      exons and at the ZFX/ZFY loci. Ninety three percent of PEP reactions with single
      amniocytes, chorionic villus cells and blastomeres were successful, and a blinded
      analysis of single lymphoblasts from affected males resulted in 93% diagnostic
      accuracy, demonstrating its applicability in preimplantation prevention of
      Duchenne muscular dystrophy. Transfer of unaffected male embryos and improved
      diagnostic reliability are achieved with the ability to perform replicate
      multilocus analyses from the same blastomere.

PMID- 8136828
TI  - A non-syndrome form of neurosensory, recessive deafness maps to the
      pericentromeric region of chromosome 13q.
AB  - Non-syndromic, recessively inherited deafness is the most predominant form of
      severe inherited childhood deafness. Until now, no gene responsible for this type
      of deafness has been localized, due to extreme genetic heterogeneity and limited
      clinical differentiation. Linkage analyses using highly polymorphic
      microsatellite markers were performed on two consanguineous families from Tunisia
      affected by this form of deafness. The deafness was profound, fully penetrant and
      prelingual. A maximum two-point lod score of 9.88 (theta = 0.001) was found with
      a marker detecting a 13q locus (D13S175). Linkage was also observed to the
      pericentromeric 13q12 loci D13S115 and D13S143. These data map this neurosensory
      deafness gene to the same region of chromosome 13q as the gene for severe,
      childhood autosomal recessive muscular dystrophy.

PMID- 8136829
TI  - Genetic associations with human longevity at the APOE and ACE loci.
AB  - In an effort to dissect the genetic components of longevity, we have undertaken
      case-control studies of populations of centenarians (n = 338) and adults aged 20
      70 years at several polymorphic candidate gene loci. Here we report results on
      two genes, chosen for their impact on cardiovascular risk, encoding
      apolipoprotein E (ApoE), angiotensin-converting enzyme (ACE). We find that the
      epsilon 4 allele of APOE, which promotes premature atherosclerosis, is
      significantly less frequent in centenarians than in controls (p < 0.001), while
      the frequency of the epsilon 2 allele, associated previously with type III and IV
      hyperlipidemia, is significantly increased (p < 0.01). A variant of ACE which
      predisposes to coronary heart disease is surprisingly more frequent in
      centenarians, with a significant increase of the homozygous genotype (p < 0.01).
      These associations provide examples of genetic influences on differential
      survival and may point to pleiotropic age-dependent effects on longevity.

PMID- 8136830
TI  - Triplet repeats strike again.

PMID- 8136831
TI  - Identification of an imprinted U2af binding protein related sequence on mouse
      chromosome 11 using the RLGS method.
AB  - A new imprinted gene has been discovered in mice using the technique of
      restriction landmark genomic scanning (RLGS) with methylation sensitive enzymes.
      Eight out of 3,100 strain-specific NotI and BssHII spots were identified as
      imprinted in reciprocal F1 hybrids. Subsequently, we isolated a genomic clone for
      one locus on proximal chromosome 11 near the Glns locus, an imprinted region in
      uniparental disomic mice, and its corresponding cDNA clone. Expression of this
      transcript from the paternal allele was established using RT-PCR of reciprocal F1
      hybrid mice. The amino-acid sequence deduced from the cDNA showed significant
      homology to the U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa
      subunit.

PMID- 8136832
TI  - ApoE and ACE genes: impact on human longevity.

PMID- 8136833
TI  - Allele specificity of DNA replication timing in the Angelman/Prader-Willi
      syndrome imprinted chromosomal region.
AB  - DNA replication within chromosome 15q11-q13, a region subject to genomic
      imprinting, was examined by fluorescence in situ hybridization. Asynchronous
      replication between homologues was observed in cells from normal individuals and
      in Prader-Willi (PWS) and Angelman syndrome (AS) patients with chromosome 15
      deletions but not in PWS patients with maternal uniparental disomy. Opposite
      patterns of allele-specific replication timing between homologous loci were
      observed; paternal early/maternal late at D15S63, D15S10 and the gamma
      aminobutyric acid receptor beta 3 subunit gene (GABRB3); and maternal
      early/paternal late at the more distal gamma-aminobutyric acid receptor alpha 5
      subunit gene (GABRA5). At the most distal locus examined, D15S12, both patterns
      of allele-specific replication timing were detected.

PMID- 8136834
TI  - Three autosomal dominant corneal dystrophies map to chromosome 5q.
AB  - The two most common autosomal dominant dystrophies of the corneal stroma are
      lattice corneal dystrophy type I and granular dystrophy. A third autosomal
      dominant stromal dystrophy (Avellino) has also been recognized. Chromosome
      linkage analysis of four families with Avellino dystrophy mapped the disease
      causing gene to chromosome 5q. Subsequent linkage analysis of two families with
      typical lattice dystrophy and two with typical granular dystrophy also revealed
      significant linkage with the same markers. Thus, each of three clinically and
      histopathologically distinct phenotypes is independently linked to 5q. The
      maximum combined lod score using all 114 affected patients was 28.6 with marker
      D5S393. None of the 14 known human amyloid-associated genes map to chromosome 5.

PMID- 8136835
TI  - A subterminal satellite located adjacent to telomeres in chimpanzees is absent
      from the human genome.
AB  - One of the significant unresolved differences between the karyotypes of humans
      and African apes is the presence of positively staining G-bands at the ends of
      many chromosome arms in the chimpanzee and gorilla but absent from human
      chromosomes. Using a telomere anchored PCR strategy, we have isolated DNA from a
      subterminal satellite, composed of a 32 basepair A-T rich repeat, from the
      chimpanzee genome that hybridizes to all the additional terminal bands and at two
      interstitial sites. The satellite is more abundant in gorillas and is not
      detected in humans or orangutans. Furthermore, there is no similarity between
      other chimpanzee telomere-junction clones and human subterminal sequences, and
      therefore the organization of sequences adjacent to telomeres is very different
      between these closely related primates.

PMID- 8136836
TI  - Direct isolation of polymorphic markers linked to a trait by genetically directed
      representational difference analysis.
AB  - We describe a technique, genetically directed representational difference
      analysis (GDRDA), for specifically generating genetic markers linked to a trait
      of interest. GDRDA is applicable, in principle, to virtually any organism,
      because it requires neither prior knowledge of the chromosomal location of the
      gene controlling the trait nor the availability of a pre-existing genetic map.
      Based on a subtraction technique described recently called representational
      difference analysis, GDRDA uses the principles of transmission genetics to create
      appropriate Tester and Driver samples for subtraction. We demonstrate the
      usefulness of GDRDA by, for example, successfully targeting three polymorphisms
      to an interval of less than 1 cM of the mouse nude locus of chromosome 11.

PMID- 8136837
TI  - Mutations in the fibrillin gene responsible for dominant ectopia lentis and
      neonatal Marfan syndrome.
AB  - Mutations in the gene coding for fibrillin on chromosome 15 (FBN1) are known to
      cause Marfan syndrome (MFS). A related disorder, dominant ectopia lentis (EL),
      has also been linked genetically to this locus. We now describe ten novel
      mutations of FBN1 resulting in strikingly different phenotypes. In addition to
      classic MFS, FBN1 mutations also give rise to EL and a severe neonatal form of
      MFS. Interestingly, the neonatal MFS mutations are clustered in one particular
      region of FBN1, possibly providing new insights into genotype-phenotype
      comparisons.

PMID- 8136838
TI  - Is DRPLA also linked to 14q?

PMID- 8136839
TI  - A new bacteriophage P1-derived vector for the propagation of large human DNA
      fragments.
AB  - We have designed a P1 vector (pCYPAC-1) for the introduction of recombinant DNA
      into E. coli using electroporation procedures. The new cloning system, P1-derived
      artificial chromosomes (PACs), was used to establish an initial 15,000 clone
      library with an average insert size of 130-150 kilobase pairs (kb). No chimaerism
      has been observed in 34 clones, by fluorescence in situ hybridization. Similarly,
      no insert instability has been observed after extended culturing, for 20 clones.
      We conclude that the PAC cloning system will be useful in the mapping and
      detailed analysis of complex genomes.

PMID- 8136840
TI  - Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian
      atrophy (DRPLA).
AB  - Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant
      neurologic disorder characterized by variable combinations of myoclonus,
      epilepsy, cerebellar ataxia, choreoathetosis and dementia. By specifically
      searching published brain cDNA sequences for the presence of CAG repeats we
      identified unstable expansion of a CAG in a gene on chromosome 12 in all the 22
      DRPLA patients examined. A good correlation between the size of the CAG repeat
      expansion and the ages of disease onset is found in this group. Patients with
      earlier onset tended to have a phenotype of progressive myoclonus epilepsy and
      larger expansions. We propose that the wide variety of clinical manifestations of
      DRPLA can now be explained by the variable unstable expansion of the CAG repeat.

PMID- 8136841
TI  - Gene targeting in normal somatic cells: inactivation of the interferon-gamma
      receptor in myoblasts.
AB  - Gene targeting in somatic cells represents a potentially powerful method for gene
      therapy, yet with the exception of pluripotent mouse embryonic stem (ES) cells,
      homologous recombination has not been reported for a well characterized, non
      transformed mammalian cell. Applying a highly efficient strategy for targeting an
      integral membrane protein--the interferon gamma receptor--in ES cells, we have
      used homologous recombination to target a non-transformed somatic cell, the mouse
      myoblast, and to compare targeting efficiencies in these two cell types. Gene
      targeted myoblasts display the properties of normal cells including normal
      morphology, ability to differentiate in vitro, stable diploid karyotype,
      inability to form colonies in soft agar and lack of tumorigenicity in nude mice.

PMID- 8136842
TI  - Isolation of genes from complex sources of mammalian genomic DNA using exon
      amplification.
AB  - Modifications to exon amplification have been instituted that increase its speed,
      efficiency and reliability. Exons were isolated from target human or mouse
      genomic DNA sources ranging from 30 kilobases (kb) to 3 megabases (Mb) in
      complexity. The efficiency was dependent upon the amount of input DNA, and ranged
      from isolation of an exon for every 20 kb to an exon for every 80 kb of target
      genomic DNA. In these studies, several novel genes and a smaller number of genes
      isolated previously that reside on human chromosome 9 have been identified. These
      results indicate that exon amplification is presently adaptable to large scale
      isolation of exons from complex sources of genomic DNA.

PMID- 8136843
TI  - Are patient smart cards the right way to go? No.

PMID- 8136844
TI  - Are patient smart cards the right way to go? Yes.

PMID- 8136845
TI  - Off and running. House health panel moves on reform; action percolating in other
      committees.

PMID- 8136846
TI  - Community health needs over 65.

PMID- 8136847
TI  - The benefit 'elite'.

PMID- 8136848
TI  - Ethics ... Americans are becoming more tolerant of some form of health care
      rationing.

PMID- 8136849
TI  - Health care R&D spending doubles overall U.S. industry averages.

PMID- 8136850
TI  - Shaping up for capitation. Dollars & sense: creating incentives to effectively
      manage change.

PMID- 8136851
TI  - Shaping up for capitation. Capitation & physicians: experienced providers say
      physician involvement is crucial to success.

PMID- 8136852
TI  - Shaping up for capitation. Managing the data. Networks retool information systems
      for capitation.

PMID- 8136853
TI  - Drug busters. There are savings in systemwide formularies, but caution is
      crucial.

PMID- 8136855
TI  - How safe is your job?

PMID- 8136854
TI  - Vision of the future? Tennessee hospitals, physicians worry over TennCare.

PMID- 8136856
TI  - Work transformation. Why the new health care imperative must focus both on people
      and processes.

PMID- 8136857
TI  - Los Angeles. Foundation approach suits physicians and hospitals.

PMID- 8136858
TI  - Home care prepares to catch wave of managed care, networking.

PMID- 8136859
TI  - Data watch. Moderate rise in hospital expenses: AHA data.

PMID- 8136860
TI  - Hospitals question the return on their TQM investment.

PMID- 8136861
TI  - Quality improvement = survival.

PMID- 8136862
TI  - Prevention: good medicine, but not good economics.

PMID- 8136863
TI  - Developing research-based tables and charts.
AB  - Authors often find it difficult to develop effective tables and charts for their
      research manuscripts. Tables often include too many columns or rows, have too
      much data, and use too many lines. Charts often have poor design, too much
      content, numbers carried out too far, and other problems. This author describes
      how to avoid these problems to develop quality tables and charts to enhance your
      research manuscript.

PMID- 8136864
TI  - Volunteers as research and publication assistants.
AB  - A common complaint among nurses is that they lack the time necessary to tackle
      large research and publication projects. This article describes how volunteers
      can be used as assistants to save you time and effort and help you get those
      projects completed and published.

PMID- 8136865
TI  - The Joint Commission's Agenda for Change: what does it mean for equipment
      managers?
AB  - As the Agenda for Change unfolds, several major changes will take place.
      Organizations seeking accreditation will face potentially greater pressure to
      improve as accreditation and performance data become more available to the public
      and payers. Future accreditation decisions will be based more on observed,
      demonstrated, and measured performance than on statements of policy and practice.
      Key to this in the survey process are the new unit-based survey and the use of
      indicators. Finally, accreditation evaluation activities provided by the Joint
      Commission will become a more persistent part of the life of accredited
      organizations. New activities will include an annual contact to update
      demographic information, the random, unannounced survey process, and frequent
      data and information exchanges based on the indicator database. The goal of these
      changes is to get closer to the real work of patient care through measurement and
      assessment of organizational competence, performance, and ability to change. The
      challenge facing clinical engineers as equipment or technology managers is to
      extend their vision of the equipment management process beyond the engineering
      needs of medical equipment. The key focus of the new Joint Commission standards
      and accreditation process is the acquisition and use of information. Equipment,
      as it becomes more complex, requires more user knowledge to be applied
      effectively. As part of the information highway, the clinical engineer of
      tomorrow must focus on the information content of the equipment being introduced
      and determine the most effective method of transferring the information into user
      "brainwave."

PMID- 8136866
TI  - Prototype expert system for infusion pump maintenance.
AB  - With today's object-oriented software, knowledge-base building becomes simple.
      Using ServiceSoft's Service Power tools, an IMED PC-1 infusion pump prototype
      expert system was built. Approximately three man-weeks of work was expended to
      build the prototype expert system providing advice on repair to the board level.
      The prototype was demonstrated to the Department of Defense, and they are
      considering the inclusion of expert systems technology in medical equipment
      maintenance as one facet of their consolidation of logistic and administrative
      functions of the four military services' health care delivery.

PMID- 8136867
TI  - Home blood pressure monitoring: a survey of potential users.
AB  - Fifty respondents were surveyed using a recently developed questionnaire designed
      to evaluate the educational needs of the users of self-monitoring blood pressure
      apparatus. The categories evaluated included each subject's background and family
      health history, general knowledge about blood pressure, lifestyle factors
      affecting blood pressure, and factors affecting the measurement of blood
      pressure, as well as questions about owning a home monitor and recalibration and
      maintenance factors. The results indicate considerable disparity between the
      subjects' levels of knowledge about lifestyle factors affecting blood pressure
      and the subjects' knowledge of factors essential to accurate self-monitoring of
      blood pressure. The implications of and need for the design of educational
      training protocols are discussed.

PMID- 8136868
TI  - Nonpharmacologic circulatory support in the brain-dead animal.
AB  - A nonpharmacologic technique for providing an artificial peripheral resistance
      enabled the canine heart to pump blood for 12 hours in a brain-dead (spinal)
      animal model. The artificial peripheral resistance was provided by binding the
      body with elastic bandage. The only other support provided was artificial
      respiration. Following the 12-hour preservation period, the hearts were
      challenged to pump by the intravenous infusion of saline. Aortic pressure,
      cardiac output (CO), oxygen uptake, body temperature, arterial Na+, K+, pH, and
      HCO3-, and transchest ECG were monitored in all five animals studied during the
      control and 12-hour preservation periods. Mean blood pressure fell to 50-60 mmHg
      following cervical cord transection, rising to above 100 mmHg when the body was
      bound with elastic bandage that restored the peripheral resistance. During the 12
      hour preservation period the average mean blood pressure fell from 118 to 60
      mmHg, at which point the average normalized CO was 34 mL/min/kg. Following the
      saline challenge, the average CO increased to 1.89 times the value at the end of
      the preservation period, representing an average normalized value of 64.3
      mL/min/kg (a typical value for the normal resting dog is 70 mL/min/kg). Body
      temperature decreased slightly in four animals and increased slightly in one. Na+
      was virtually unchanged throughout the control and preservation periods, but K+
      increased slightly in all animals, exceeding 5 mEq/L in one animal after 8.5
      hours and in another after 10 hours. HCO3- was almost constant in all animals, as
      was pH. However, the pH was elevated during the preservation period due to slight
      overventilation to assure a high oxygen saturation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8136869
TI  - Hardware-software approach for neonatal cardiovascular risk estimation.
AB  - Genetic risk is a primary contributing factor to the predisposition of a newborn
      child to elevated blood pressure later in life. To determine whether there is a
      correlation between potential genetic risk as established by family history and
      measured physiologic variables in the neonate, the systolic and diastolic blood
      pressures and heart rates of 150 newborn babies were automatically monitored at
      about 30-minute intervals for 48 hours with a Nippon Colin device, starting early
      after birth. Circadian parameters (obtained by the linear least-squares fit of a
      24-hour cosine curve to each individual series) and descriptive statistics for
      the three circulatory variables were used in a multiple-regression analysis to
      compute a linear prediction function for a neonatal cardiovascular risk score.
      This score was obtained for each neonate on the basis of the presence or absence
      of overt cardiovascular disease, elevated blood pressure, or obesity across two
      generations, those of the newborn's parents and grandparents. Results from
      multiple regression indicate that the best model for prediction of the risk score
      includes the circadian amplitudes of systolic and diastolic blood pressure, the
      circadian range of heart rate, and the 90% range and standard deviation of
      diastolic blood pressure. The multiple correlation coefficient between the
      predicted and the computed risk scales is 0.666, a value that, although
      statistically significant (p < 0.001), is still low for a generalized practical
      use of the model in predicting risk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136870
TI  - NFPA 99 standard for health care facilities--overview of 1993 changes.

PMID- 8136871
TI  - [Writing difficulty syndrome--a rare symptom complex involving the median nerve
      and the carpal tunnel].
AB  - Authors describe the cases of two patients, suffering from the rare, however
      frequently not diagnosed real writing spasm. In these patients surgery brought
      healing or significant improvement. After a review of the literature the
      symptoms, the possibilities of diagnosis and therapy are described. With their
      paper they want to call attention to this not well known disease.

PMID- 8136872
TI  - [Substitution of the thumb by transplantation of the second toe].
AB  - Authors perform for the substitution of the thumb beside several other operations
      the transplantation of the second toe. The transplantation is carried out with
      the reconstruction of the arterial circulation, built on the I. metatarsal
      artery. Until now 18 substitutions of the thumb were carried out. The etiology of
      the lack of the toe is variable, in the great majority it is of traumatic origin
      however purulent process and attempt of suicide occur. With the observation of
      the rules of structural reconstruction good functional result may be reached. In
      more than a third of the cases both the sensitivity and the mobility are
      excellent. The use of this method is suggested first of all in cases where
      alternative substituting operations are out of question.

PMID- 8136873
TI  - [Experimental study of postoperative scarring around the tendon sheath].
AB  - Authors have compared two kind of exposures of the flexor tendons. The results
      were assessed by measuring the flexion oft the given finger on pulling, by light
      and electron microscopic examination. It was found that in fingers where the
      tendon sheat was detached from the subcutis the scarring was greater and its
      effect, limiting the motion has its maximum on the fourth postoperative week. It
      is raised that the role of the tendon sheat in respect of the success of the
      flexor tendon reconstruction is mainly mechanic and most effective if its highly
      integrated connection with its surrounding is not disturbed.

PMID- 8136874
TI  - [Submicroscopic study of degeneration and regeneration following experimental
      nerve transplantation].
AB  - Authors, as a continuation of a former series of experiments, examined the fate
      of free autologous nerve grafts. It was found that the transitory state without
      circulation does not influence the start of regeneration and its temporal process
      in the graft. They call attention to the important role of the Schwann cells in
      the regeneration. 8-10 weeks postoperatively a complete remyelinization was
      observed even in the distal stump.

PMID- 8136875
TI  - [Management of calcaneus fractures at the authors' department].
AB  - Since 1st January 1986 the authors have been using Zadravecz's method for the
      classification and treatment of intraarticular calcaneal fractures. Evaluation of
      132 cases: Based on their good results, they propagate the use of this method for
      the treatment of calcaneal fractures. After reviewing results covering a period
      of more than five years, they neither found late bone-height loss nor other
      complications.

PMID- 8136876
TI  - [Questions about the two-stage reconstruction of flexor tendon injuries. IV.
      Clinical experience].
AB  - Authors report on clinical experiences gained with the two stage flexor tendon
      transplantation described by Hunter. Their modifications are described and the
      results given in details. They touch also upon the indications of the procedure
      considering the preoperative evaluation. Other procedures are also offered for
      injuries with bad prognosis and the future trends of investigation, held to be
      important, are mentioned.

PMID- 8136877
TI  - [Management of malacia of the os lunatum by implantation of a dorsal metacarpal
      vascular bundle].
AB  - In the treatment of malacia of the lunate bone, beside the prosthesis and
      procedures aiming the decrease of load, the revascularization of the bone is the
      third basic therapeutic principle. One possibility of the later, not yet current
      in this country, is the implantation of the metacarpal vascular bundle in the
      lunate bone. As far as we know we were the first to perform this operation in
      Hungary. In this paper our first cases are described together with a detailed
      description of the operative technique and we would call at the same time to
      further common examinations.

PMID- 8136878
TI  - [Osteogenetic cells in myositis ossificans].
AB  - We have used the lectins Arachis hypogaea (PNA), Canavalia ensiformis (Con A) and
      Triticum vulgaris (WGA) for the examination of bone forming cells in 8 variously
      differentiated cases of myositis ossificans. The development of myositis
      ossificans could be characterized with the appearance of a WGA binding cell
      population. In this cell population the lectin binding spots may be found in the
      perinuclear cytoplasm, possibly in the Golgi complex. The lectin binding of the
      bone forming cells has disappeared in the ripe myositis ossificans. We think that
      the WGA binding cell population may be equal with the progenitor cells, wandering
      in form the stroma ot the bone marrow and that the ability of WGA binding may be
      a characteristic developmental marker of these cells.

PMID- 8136879
TI  - [Questions concerning two-stage reconstruction of injured flexor tendons. III.
      Ultrastructure of the tenosynovium in the pseudo-tendon sheath created by using a
      silicone rod].
AB  - Authors have investigated the ultrastructure of the pseudo tendon sheath, formed
      with silicon rod and man. They have observed a superficial structure, resembling
      the normal tendon sheath in scanning electron microscopic examination. With
      transmission electron microscopy phagocyte "A" type and secretion "B" type
      synovial cells were found. Authors state that the newly formed tenosynovium has
      an important role in the nutrition of the tendon graft and the prevention of
      adhesions.

PMID- 8136880
TI  - [Structure of external fixators].
AB  - Authors described the development of the construction of fixateur externes
      supported by historical facts, analyse the biomechanical problems of the fixateur
      osteosyntheses, illustrated by drawings. They propose mountings, of modern
      montage proving its rightness. Finally a collection of synonyms is given to clear
      the nomenclature of the several montages.

PMID- 8136881
TI  - [AIDS and the obstetrician-gynecologist].

PMID- 8136882
TI  - [Plasma tumor markers].

PMID- 8136883
TI  - [A sexo-analytic view on homosexuality].
AB  - After having defined the terminology, the author attempts to identify
      homosexuality through the sexual individuation process and to trace its different
      ontogenic inconsistencies. A typology based on non conformity of gender and the
      heterophobia is suggested. Two clinical case examples will be given to further
      illustrate the sexoanalytic treatment of egodystonic homosexuality.

PMID- 8136884
TI  - [The regulation of endometrial and trophoblastic metalloproteinases during
      blastocyst implantation].
AB  - The trophoblastic cells of the blastocyst and of the placenta express an invasive
      phenotype. These cells produce and secrete metalloproteinases which are capable
      of digesting the extracellular matrix and invade it. The different endometrial
      cells produce the same enzymes and favour thus the implantation process. Among
      the numerous endometrial factors that control trophoblastic invasion, the
      components of the extracellular matrix such as laminin and fibronectin, play an
      important role. These glycoproteins, control the proteolytic activity of the
      invading cells by binding to their receptors (integrins) expressed on the cell
      membrane. When these receptors are distributed in a non polarised way they don't
      bind their ligands and the cells secrete proteases and invade the endometrium.
      Conversely, when the receptors are clustered, they bind to their ligands and the
      cell's invasive behaviour and protease secretion is inhibited. The endometrial
      extracellular matrix is thus a potent regulator of trophoblast invasion.

PMID- 8136885
TI  - [Electro-conization with the diathermic loop. Indications and results].
AB  - The experiment of electro-conization with diathermic loop was effected on 185
      patients. The indications are represented by: a) low grade lesions: 21 cases
      (11.3%) only when the squamo-columnar junction was into the endocervix; b) CIN 2:
      44 cases (23.7%): c) CIN 3: 118 cases (63.7%); d) cyto-histologic discordance: 2
      cases. After one year, the following results could be noted: 94.1% of the
      patients were cured, only 11 out of the 185 presented a recurrence (or
      persistence). It seemed interesting to us to study the factors which could
      influence the "in sano" (Free margin)/or not character of the resection. It
      appeared that the surface of the lesion did not seem to influence its
      histological result since we got: 83%, 96%, 94.5% and 92.3% of "in sano"
      conizations to be correlated with a lesion surface equal to 1/4, 2/4, 3/4, 4/4 of
      the cervical area. The second factor to be studied was the patients' age. So from
      15 to 25 years (96%) of the resections were "in sano". There from 26 to 35 (92%),
      and from 36 to 45 (91.9%). Among post-menopausal women from 46 to 55 years old
      only 86.4% of electro-conizations were "in sano". Histologic alterations of the
      histologic specimen were noted in two cases (1%), the interpretation was easy and
      clear in the other cases. What about the complications? In 2 cases a moderate
      stenosis was to be noted; in 2 other cases: post-operative hemorragiae which were
      treated by a selective electro-coagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8136886
TI  - [Emotional and psychiatric postpartum complications].
AB  - The three emotional and psychiatric complications of post-partum are: puerperal
      psychoses; post-natal depressions; and post-partum blues. Puerperal psychoses
      (prevalence = 0.2%) are now well known in their clinical and therapeutic aspects.
      Much less known are the post-natal depressions, in spite of their high incidence
      (10 to 20% of women). The consequences upon the life of patients and mother-child
      bond are still ignored. These depressions are too rarely adequately treated.
      Finally, post-partum blues is to be recognized for a preventive purpose, its
      intensity being a predictive factor of post-natal depression.

PMID- 8136887
TI  - [Endometrial cell cultures: their value in the understanding of the implantation
      mechanisms].

PMID- 8136888
TI  - Multiple disorder diagnosis with adaptive competitive neural networks.
AB  - Backpropagation neural networks have repeatedly been used for diagnostic problem
      solving, but have not been demonstrated to work well when multiple disorders are
      present. We hypothesized that letting nodes in a backpropagation neural network
      compete to be part of a diagnostic solution would produce better performance than
      the use of existing backpropagation methods. To test this hypothesis, we derived
      an error backpropagation learning rule that can be used with competitive units
      (competitive backpropagation). Artificial neural networks were then trained using
      both this new learning rule and standard error backpropagation on a specific
      medical diagnosis problem: identification of the location of damage in the brain
      given a set of examination findings. Training samples included solely
      'prototypical' cases where a single location of damage is present. The trained
      networks were then tested with atypical cases where the manifestations of more
      than one disorder were present or only a single manifestation was present.
      Networks employing competition among units were found to perform qualitatively
      better with these multiple-disorder cases than standard networks and also to
      perform better on single-manifestation cases. The reasons for this are explained.
      The competitive backpropagation learning rule described here provides a promising
      new tool for adaptive diagnostic problem-solving.

PMID- 8136889
TI  - Towards a statistically oriented decision support system for the management of
      septicaemia.
AB  - The first decision-support system designed for the management of septicaemia was
      MYCIN. Although MYCIN played a vital role in the conception of knowledge-based
      systems, it never became an established clinical system. This paper describes an
      alternative decision-support system for septicaemia management currently under
      development at St. Thomas' Hospital (London) where a large database of
      septicaemia episodes has been compiled. The three statistical approaches that
      have been considered are described. These are (i) relative frequencies, (ii) the
      naive Bayes method and (iii) logistic regression. We also discuss how the concept
      of probabilistic influence diagrams could be of benefit to the development and
      implementation of the decision-support system.

PMID- 8136890
TI  - Neural network based classification of single-trial EEG data.
AB  - Standard Back Propagation (BP), Partially Recurrent (PR) and Cascade-Correlation
      (CC) neural networks were used to predict the side of finger movement on the
      basis of non-averaged single trial multi-channel EEG data recorded prior to
      movement. From these EEG data, power values were calculated and used as
      parameters for classification. The results obtained on three subjects show that
      the Cascade-Correlation neural network is an appropriate choice for neural
      network based classification of spatio-temporal single-trial EEG patterns. It is
      fast, stable and able to discover and recognize underlying dynamics of rhythmic
      activities within the alpha band which precede execution of hand movements.

PMID- 8136891
TI  - Connectionist expert systems as medical decision aid.
AB  - In this paper neural networks are used as associative memories to build an expert
      system for aiding medical diagnosis. As in expert systems using symbolic
      manipulation, the knowledge is introduced by a knowledge engineer using a
      collection of known cases. The system has an object-oriented approach to
      knowledge organization and the resulting network topology. Fuzzy sets are used to
      interpret connection values and/or excitation state of the units. The main result
      is that the proposed neural network allows not only finding a solution in some
      cases, but also suggests obtaining more clinical data if the data available is
      insufficient to reach a conclusion. This approach is illustrated by examples.

PMID- 8136892
TI  - APP expression in primary neuronal cell cultures from P6 mice during in vitro
      differentiation.
AB  - Primary neuronal cell cultures from P6 mice were investigated in order to study
      amyloid protein precursor (APP) gene expression in differentiating neurons.
      Cerebellar granule cells which strongly express APP 695 allowed the
      identification of three distinct isoforms of neuronal APP 695. The high-molecular
      weight form of APP 695 is sialylated. The expression pattern of neuronal APP 695
      changes during in vitro differentiation. Sialylated forms become more abundant
      upon longer cultivation time. The secreted forms of sialylated, neuronal APP 695
      are shown to comigrate with APP isolated from cerebrospinal fluid. We suggest
      that the different sialylation states of APP 695 may reflect the modulation of
      cell-cell and cell-substrate interactions during in vitro differentiation and
      regeneration.

PMID- 8136893
TI  - Heparan sulfate expression patterns in the amyloid deposits of patients with
      Alzheimer's and Lewy body type dementia.
AB  - Heparan sulfate (HS), along with serum amyloid P component, has been identified
      in all types of amyloid investigated so far, regardless of the type of amyloid
      protein deposited. To assess whether unique or specific HS proteoglycans (HSPGs)
      may be involved in the formation of these lesions, we have investigated the
      accumulation of several distinct HSPG epitopes in the cerebra of patients with
      different forms of neurodegenerative disease. A panel composed of several
      antibodies revealed distinctive patterns of HSPG accumulation. In patients with
      dementia of the Lewy body type, the burned-out-type plaques and preamyloid-type
      plaques were strongly stained by both the anti-HS 'chain' and anti-HS 'stub'
      antibodies, but by none of the available anti-core protein antibodies. In
      Alzheimer's disease, the preamyloid-type plaques, dense-cored-type plaques,
      neuritic-type plaques and the neurofibrillary tangles were stained by the anti
      'stub' antibody. The anti-'chain' and the anti-core protein antibodies, in
      contrast, failed to stain the preamyloid-type plaques and burned-out-type
      plaques, but stained the neuritic-type plaques in these patients. These data
      suggest differences in the types of HS and HSPG (fragments) that accumulate in
      amyloid lesions that may hallmark neurodegenerative disorders of different
      etiologies.

PMID- 8136894
TI  - Growth hormone secretion in Alzheimer's disease: studies with growth hormone
      releasing hormone alone and combined with pyridostigmine or arginine.
AB  - There is evidence that GH secretion is reduced in normal elderly subjects as well
      as in patients with Alzheimer's disease (AD). To clarify the mechanisms
      underlying this GH hyposecretory state in 14 elderly subjects (age 65-75 years)
      and 15 AD patients (age 61-78 years), we studied the effects of both
      pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine
      (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic
      somatostatin, on GH response to GHRH (1 microgram/kg i.v.). The GH response to PD
      alone was also studied. Twenty-two young healthy volunteers were studied as
      control group. Basal GH levels were similar in young, elderly and AD subjects
      (0.7 +/- 0.2, 0.8 +/- 0.2 and 0.9 +/- 0.2 microgram/l). IGF-I levels were lower
      (p < 0.005) in elderly (73.9 +/- 8.2 microgram/l) and in AD subjects (108.0 +/-
      5.9 micrograms/l) than in young subjects (288.7 +/- 22.1 micrograms/l); however,
      they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD
      induced GH release did not significantly differ in young, elderly and AD subjects
      while the GH responses to GHRH in the elderly (AUC: 297.9 +/- 49.2 micrograms/l)
      and in AD subjects (437.6 +/- 93.5 micrograms/l/h) were lower (p < 0.01) than in
      young subjects (658.6 +/- 100.1 micrograms/l/h). PD potentiated the GH response
      to GHRH both in elderly and in AD subjects (901.7 +/- 222.4 and 1,070.3 +/- 207.2
      micrograms/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those
      recorded in young subjects (2,041.1 +/- 245.6 micrograms/l/h).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8136895
TI  - Neuropsychological heterogeneity in mild Alzheimer's disease.
AB  - In order to investigate neuropsychological differences in patients with mild AD,
      we carried out a pilot study on 28 patients with a clinical diagnosis of mild
      dementia (CDR: 0.5-1) using an extensive neuropsychological battery, in
      comparison with 28 normal controls. The results of a cluster analysis, applied on
      the neuropsychological variables, showed the existence of at least two main
      subgroups of patients. Cluster 1 patients had a mean age of 61.1 years and showed
      a greater impairment on measures of language, abstract reasoning and verbal
      fluency; cluster 2 patients, with a mean age of 72.0, had more severe impairment
      in memory function. These preliminary results may suggest the existence of
      different subtypes of AD characterized by selective neuropsychological
      deterioration in the early stages of the disease.

PMID- 8136896
TI  - Epidemiology of depressive symptoms in elderly primary care attenders.
AB  - 408 elderly primary care attenders were screened using the Geriatric Depression
      Scale (GDS) and the 30-item General Health Questionnaire (GHQ). 36% were
      identified as 'cases' on the GDS and 32% on the GHQ. The 'cases' and a random
      sample of 'non-cases' were interviewed using the Geriatric Mental State
      Examination (GMS), the Bedford College Life Events and Difficulties Interview
      (LEDS), the National Adult Reading Test (NART), and systematic inquiry concerning
      physical health. Sensitivity and specificity of the GDS were 85% and 68%, and of
      the GHQ 77% and 67%. General practitioner identification of cases showed a
      sensitivity of 78% and a specificity of 60% against the GMS. Depression was
      significantly associated with life events, chronic difficulties, poor physical
      health and current lack of a confiding relationship. Subjective complaints of
      depression were associated with low premorbid intelligence and lifelong lack of a
      confiding relationship. The availability of a confiding relationship appears to
      have a protective effect against depressive illness associated with life events
      and chronic difficulties.

PMID- 8136897
TI  - Brain perfusion imaging in Parkinson's disease and Alzheimer's disease
      demonstrated by three-dimensional surface display with 123I-iodoamphetamine.
AB  - We reconstructed three-dimensional (3D) surface images from data from single
      photon emission computed tomography (SPECT) with N-isopropyl-p[123I]
      iodoamphetamine (123I-IMP) in 29 patients with Parkinson's disease, 16 patients
      with Alzheimer's disease and 11 normal control subjects. In patients with
      nondementing Parkinson's disease, perfusion defects were frequently found in the
      parietal cortical region at a threshold value of 65%. In demented Parkinson's
      disease patients, perfusion defects were frequently noted at threshold of 45-65%,
      and were more marked in the bilateral temporal and parietal cortices. In
      Alzheimer's disease, perfusion defects were similar to those found in dementing
      Parkinson's disease. These results suggest that dementia in Parkinson's disease
      is related to the perfusion reduction of the temporoparietal cortex, and may
      support the view that Parkinson's disease and Alzheimer's disease overlap in some
      patients. A 3D display of an 123I-IMP brain tomogram may be useful for detecting
      cortical lesions in patients with dementia or cognitive impairment.

PMID- 8136898
TI  - Age at onset and SPECT imaging in Alzheimer's disease.
AB  - It is generally accepted that presenile Alzheimer's disease (AD) has faster
      progression and severer clinical manifestation than senile onset AD. Recently a
      relative left frontal hypoperfusion was only found in patients with presenile AD
      by using SPECT imaging. The aim of the present report was to ascertain whether
      the same conclusion could be drawn matching the population with respect to the
      severity of the cognitive profile and disease duration. Twenty subjects for each
      group were studied with SPECT and no differences emerged between groups. It is
      postulated that presenile and senile onset AD represent aspects of the same
      biological process.

PMID- 8136899
TI  - 17th International Symposium on Column Liquid Chromatography. Hamburg, Germany,
      May 9-14, 1993. Part II. Proceedings.

PMID- 8136900
TI  - Sensitive determination of N-terminal prolyl peptides by high-performance liquid
      chromatography with laser-induced fluorescence detection.
AB  - Short-chain peptides with an N-terminal proline (Pro-Gly, Pro-Ile, Pro-Gly-Gly,
      Pro-Leu-Gly-NH2, and Pro-Thr-Pro-Ser-NH2, etc.) were determined by HPLC with
      laser-induced fluorescence (LIF) detection. The peptides were quantitatively
      labelled with 4-(N,N-dimethylaminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD
      F) at 50 degrees C after 1 h in a 0.1 M borax (pH 9.3)-acetonitrile mixture. The
      rate of reaction decreases inversely with the molecular weight of the peptides.
      The mean value of fluorescent emission of the resulting DBD-peptides and DBD
      peptide amides was 573 nm (excitation, 453 nm). The proline peptides, including
      bioactive peptides such as Pro-Leu-Gly-NH2 (release inhibitor of melanocyte
      stimulating hormone), Pro-Thr-Pro-Ser-NH2 (IgA1 proteinase inhibitor) and Pro-Asp
      Val-Asp-His-Val- Phe-Leu-Arg-Phe-NH2 [FMRF amide-like (Phe-Met-Arg-Phe-NH2)
      neuropeptide], were well separated by reversed-phase HPLC with water-acetonitrile
      containing 0.1% trifluoroacetic acid (TFA). The acetonitrile concentration in the
      mobile phase had a profound effect upon the retention times, and the capacity
      factors (k') were dependent on the hydrophobicity of the peptides. The structure
      of DBD-Pro-Leu-Gly-NH2 was identified by LC-atmospheric pressure chemical
      ionization MS. The chromatographic detection limits (S/N = 2) of the peptides
      with a 15-mW argon-ion laser at 488 nm were in the 6-28 fmol range. The detection
      limits were improved to 2-5 fmol with a microbore column. The detectability was
      two orders of magnitude higher than with a conventional fluorescence detector
      using xenon arc lamp.

PMID- 8136901
TI  - Column-switching liquid chromatographic method for the simultaneous determination
      of iothalamic acid and creatinine in biological fluids.
AB  - A column-switching liquid chromatographic method for simultaneous determination
      of iothalamate and creatinine in human serum and urine was developed. Iothalamate
      and creatinine were separated on a weakly acidic ion-exchange column (C1) by ion
      exclusion chromatography and iothalamate excluded from the column was purified by
      gel chromatography on a hydrophilic gel column (C2) and then by ion-exchange
      chromatography on a weakly basic ion-exchange column (C3). Creatinine that was
      eluted from C1 after iothalamate was transferred to a hydrophilic gel column (C4)
      and then to a strongly acidic ion-exchange column (C5). The mobile phase for C1
      C4 was a pH 3.8 propionate buffer (propionic acid-NaOH = 0.35 + 0.035 mol/kg in
      water) and a pH 5.6 propionate buffer (propionic acid-NaOH = 0.04 + 0.035 mol/kg
      in water) was used for C5. Diluted serum and urine samples could be injected
      directly on to C1, as the matrix of C1 is hydrophilic and C1 is backflushed after
      the transfer of the creatinine fraction from C1 to C4. Iothalamate and creatinine
      in the eluates were determined by measuring their ultraviolet absorption at 245
      and 234 nm, respectively. The precision (R.S.D.) of the chromatographic method
      was 1.6% (n = 7) and 0.36% (n = 6) for diluted serum and urine with iothalamate
      concentrations of 1.0 and 10.0 mumol/l, respectively, and 0.85% (n = 7) and 0.55%
      (n = 7) for diluted serum and urine with creatinine concentrations of 5.77 and
      272 mumol/l, respectively.

PMID- 8136902
TI  - Purification and analytical characterization of an anti-CD4 monoclonal antibody
      for human therapy.
AB  - A purification process for the monoclonal anti-CD4 antibody MAX.16H5 was
      developed on an analytical scale using (NH4)2SO4 precipitation, anion-exchange
      chromatography on MonoQ or Q-Sepharose, hydrophobic interaction chromatography on
      phenyl-Sepharose and gel filtration chromatography on Superdex 200. The
      purification schedule was scaled up and gram amounts of MAX.16H5 were produced on
      corresponding BioPilot columns. Studies of the identity, purity and possible
      contamination by a broad range of methods showed that the product was highly
      purified and free from contaminants such as mouse DNA, viruses, pyrogens and
      irritants. Overall, the analytical data confirm that the monoclonal antibody
      MAX.16H5 prepared by this protocol is suitable for human therapy.

PMID- 8136903
TI  - On-line solid-phase extraction with automated cartridge exchange for liquid
      chromatographic determination of lipophilic antioxidants in plasma.
AB  - A fully automated liquid chromatographic method is described based on a Prospekt
      solid-phase extraction unit for the analysis of lipophilic indenoindolic
      antioxidants in plasma. Plasma samples, mixed with internal standard, were
      injected onto C8-cartridges. After washing, the samples were eluted and
      transferred to a C8-analytical column, where separation was performed. The eluent
      was monitored by electrochemical detection. Owing to the nature of the drugs
      investigated care had to be taken to avoid adsorption losses in vials and
      capillaries. The method, which was found to give excellent recoveries (100.9%, n
      = 8) and repeatability (R.S.D. +/- 1.7%), is time-saving compared to a previously
      used assay with sample work-up by liquid-liquid extraction.

PMID- 8136904
TI  - Purification of human tumour necrosis factor by membrane chromatography.
AB  - The recombinant human tumour necrosis factor alpha from an extract of Escherichia
      coli was enriched to homogeneity according to specific activity and sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis by purification using anion
      exchange HPLC and hydrophobic interaction HPLC. Parallel experiments with the
      same separation methods, but carried out with membrane chromatography on compact
      discs, gave similar results in terms of yield and purity of the product. The
      active form of the protein is a trimer. The second isolation step, hydrophobic
      interaction chromatography, causes dissociation of the trimer into monomers and a
      partial loss of the biological activity of the protein. The phenomenon occurs on
      both the column and the disc. This in turn indicates strongly that the
      dissociation of the protein is a consequence of interaction between the samples
      and the hydrophobic ligand, and is not caused by non-specific interaction with
      the matrix.

PMID- 8136905
TI  - Determination of aflatoxins in food by use of an automatic work station.
AB  - An automated HPLC method with postcolumn derivatization is described for the
      determination of aflatoxins B1, B2, G1 and G2 after an immunoaffinity column
      clean-up. It can be used for the determination of aflatoxins in a variety of
      foodstuffs such as nuts, nut-like products (pistachios, almonds, etc.) and dried
      fruit. The aflatoxins are extracted with methanol-water, followed by a filtration
      step. Dilution of the extract, mixing, immunoaffinity column clean-up, elution of
      the aflatoxins and optional on-line HPLC are performed by an automatic work
      station (Zymark BenchMate). The subsequent HPLC analysis includes a postcolumn
      derivatization step with iodine solution and fluorimetric detection. The method
      compared well with manual techniques and another automated method.

PMID- 8136906
TI  - High-performance liquid chromatographic method for the simultaneous detection of
      malonaldehyde, acetaldehyde, formaldehyde, acetone and propionaldehyde to monitor
      the oxidative stress in heart.
AB  - Lipid peroxidation (LPO) is the oxidative deterioration of polyunsaturated fatty
      acids (PUFA) with the production of lipid hydroperoxides, cyclic peroxides,
      cyclic endoperoxides, and finally fragmentation to ketones and aldehydes
      (including malonaldehyde, MDA). Estimation of LPO through MDA formation measured
      by assaying thiobarbituric acid (TBA) reactive products remains the method of
      choice to study the development of oxidative stress in tissues. However, MDA
      estimation by TBA reactive products is non-specific and often gives erroneous
      results. In this report we describe a method using high-performance liquid
      chromatographic separation to estimate MDA, formaldehyde (FDA), acetaldehyde
      (ADA), acetone, and propionaldehyde (PDA), the degradation products of oxygen
      derived free radicals (ODFR) and PUFA, as presumptive markers for LPO. Oxidative
      stress was induced in the tissue by perfusing an isolated rat heart with hydroxyl
      radical generating system (xanthine + xanthine oxidase + FeCl3 + EDTA). The
      coronary effluents 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 three different wavelengths (307, 325
      and 356 nm) using a Waters M-490 multichannel UV detector and collected for gas
      chromatography-mass spectrometry (GC-MS) analysis. The peaks were identified by
      cochromatography with DNPH derivatives of authentic standards, peak addition, UV
      pattern of absorption at the three wavelengths, and by GC-MS. The retention items
      of MDA, FDA, ADA, acetone, and PDA were 5.3, 6.6, 10.3, 16.5, and 20.5 min,
      respectively. The results of our study indicated progressive increase of all five
      lipid metabolites as a function of the duration of ODFR perfusion. Hydroxyl
      radical scavengers, superoxide dismutase plus catalase, completely inhibited the
      formation of these lipid metabolites, demonstrating that the release of lipid
      metabolites from the isolated heart was indeed in response to oxidative stress.
      Since MDA, FDA, ADA, acetone, and PDA are the products of ODFR-PUFA interactions,
      this method allows proper estimation of LPO which monitors the oxidative stress
      developed during the reperfusion of ischemic myocardium.

PMID- 8136907
TI  - Applications of amino acid derivatization with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate. Analysis of feed grains, intravenous solutions and
      glycoproteins.
AB  - Primary and secondary amines are rapidly labelled by 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate to form highly fluorescent asymmetric urea
      derivatives which are readily amenable to analysis by liquid chromatography.
      Derivatization consists of a simple, one-step procedure, and the resulting
      labelled amines can be analyzed without further cleanup. The adducts are
      extremely stable with no discernible loss in response after storage for one week
      at room temperature, making the reagent an ideal candidate for pre-column amino
      acid analysis. Chromatographic methods for protein hydrolysates have been
      developed for the analysis of samples containing many unusual amino acids
      including a number of cysteine derivatives, collagen hydrolysates containing
      hydroxyproline and hydroxylysine, performic acid oxidized samples and
      glycoprotein hydrolysates containing glucosamine and galactosamine. Samples with
      potentially interfering matrix components such as hydrolyzed feed grains and
      intravenous solutions are readily analyzed and are quantified with average per
      cent relative standard deviations in the 1-2% range. Comparative data on these
      samples are in good agreement with either ion-exchange amino acid analysis or
      label information.

PMID- 8136908
TI  - Analysis of derivatized peptides by capillary electrophoresis.
AB  - Thirteen synthetic prothrombin leader peptides differing only in C terminus were
      analyzed by capillary electrophoresis. These peptides were derivatized using the
      novel, fluorescent derivatizing agent, 6-aminoquinolyl-N-hydroxysuccinimidyl
      carbamate. Derivatized peptides were detected using fluorescence and ultraviolet
      absorption signals, and underivatized peptides were detected using ultraviolet
      absorbance at 185 nm. Data are presented which compare the analysis of the
      derivatized and underivatized peptides.

PMID- 8136909
TI  - Indirect fluorescence determination of lactate and pyruvate in single
      erythrocytes by capillary electrophoresis.
AB  - A scheme of using fluorescein as the fluorophore for indirect detection of anions
      was demonstrated. This system is quite stable at a fluorescein concentration of
      100 microM even without any other buffer components. Different injection modes
      affect the limit of detection (LOD). A LOD of about 20 amol was obtained for
      lactate under optimal conditions. Lactate and pyruvate in the intracellular fluid
      of erythrocytes were measured in this manner. The average amounts in a single
      erythrocyte for lactate and pyruvate are 1.3 and 2.1 fmol, respectively, or a
      ratio of 1.6 for pyruvate to lactate. Variations of the absolute amounts and the
      ratios are fairly large among a group of 27 cells examined. This is consistent
      with the difference of cells in size and composition. Although the migration
      times changed by up to 20% during a series of runs from the influence of
      concomitants in the cells, the migration time ratio was maintained around 1.072
      with 3% relative standard deviation.

PMID- 8136910
TI  - Preparation and characterization of a stable polyacrylamide sieving matrix-filled
      capillary for high-performance capillary electrophoresis.
AB  - A stable sieving matrix of polyacrylamide filled in a capillary was developed.
      The inner wall of a fused-silica capillary was covalently bonded with a linear
      polyacrylamide through Si-C linkages, in which cross-linked polyacrylamide gel or
      linear polyacrylamide solution was filled. The stability of the coating was
      examined by exposure of the capillaries to alkaline buffer (pH 8) for up to 30
      days. Compared with the coatings with linear polyacrylamide bonded through
      siloxane linkages, the present capillary markedly reduced the electroosmotic
      flow. Thus, the sieving matrix in the capillary was stabilized, resulting in a
      prolonged lifetime of the capillary and good reproducibility of separations. The
      migration behaviours of oligonucleotides were compared for the cross-linked gel
      and linear polyacrylamide solution at the same concentration.

PMID- 8136911
TI  - Kinetic study of the adsorption of human serum albumin on immobilized antibody
      using the split-peak effect in immunochromatography.
AB  - The split-peak effect was used to determine the association rate constant of the
      antigen-immobilized antibody reaction. The amount of immobilized human serum
      albumin antibody on the chromatographic support was varied in order to find the
      optimal conditions to reduce the mass transfer contribution in the stagnant
      mobile phase fluid and measure the effective association rate constant of human
      serum albumin with the immobilized antibody. Kinetic studies as a function of
      flow-rate demonstrate the validity of the method consisting in determining the
      association rate constant from measurements performed on columns of various
      capacities. These experiments show that limitations due to mass transfer to the
      surface of the adsorbent are minimized at high flow-rates and for a low density
      of immobilized ligand.

PMID- 8136912
TI  - Liquid chromatographic-mass spectrometric studies on the enzymatic degradation of
      gonadotropin-releasing hormone.
AB  - Gonadotropin-releasing hormone (GnRH) derivatives are used in cancer therapy, but
      relatively little is known about their metabolic fate in the organism. This paper
      describes the application of high-performance liquid chromatography combined with
      electrospray mass spectrometry to identify the degradation products resulting
      from the incubation of two GnRH analogues, D-Phe6-GnRH and DSer(OtBu)6-desGly10
      GnRH-ethylamide (buserelin) with rat kidney membranes. Reversed-phase columns
      were applied with gradient elution using a flow-rate of ca. 2 microliters/min to
      the mass spectrometer. Post- and precolumn stream splitting were employed to
      adjust the flow-rates for columns of 2 and 0.32 mm I.D. The pattern of peptide
      degradation products obtained with this method indicates that a defined
      proteolytic membrane enzyme system is responsible for these catabolic processes.

PMID- 8136913
TI  - High-performance liquid chromatography of amino acids, peptides and proteins.
      CXXXIII. Peak tracking of peptides in reversed-phase high-performance liquid
      chromatography.
AB  - A peak tracking algorithm for peptide analysis has been developed based on a
      normalised spectral overlay method which directly compares the UV spectra of any
      two chromatographic peaks. Additionally, the algorithm compares the spectrum of
      each peak in the first chromatogram with the spectra of every peak in the second
      chromatogram to determine the best cross-match. The sensitivity of the technique
      was further enhanced by incorporation of the primary and secondary derivative
      spectra for cross-match normalisation. The utility of the software was
      demonstrated by its application to the analysis of tryptic digests of porcine
      growth hormone. Peptide solutes could be identified and tracked in chromatograms
      generated with various column types, gradient times, mobile phase types and
      temperatures. These results therefore constitute the initial stages of
      development of a more robust approach to the optimisation of the resolution,
      detection and characterisation of peptides and proteins separated by HPLC
      techniques.

PMID- 8136914
TI  - High-performance liquid chromatographic separation of cis-trans isomers of
      proline-containing peptides. II. Fractionation in different cyclodextrin systems.
AB  - beta-Cyclodextrin-bonded silica is demonstrated to be a suitable stationary phase
      for high-performance liquid chromatography of conformational isomers of proline
      containing peptides. In contrast to reversed-phase chromatography, the principle
      of inclusion complexation shows significant selectivities in conformer resolution
      based on a variety of interactions. New results of inclusion HPLC of biologically
      active oligopeptides related to beta-casomorphin on stationary phases containing
      bonded cyclodextrins of different internal diameters indicate a steric
      discrimination process during the conformer separation. beta-Cyclodextrin used as
      a mobile phase additive in reversed-phase systems is shown to offer the
      opportunity to investigate conformational changes using commercially available
      reversed-phase columns.

PMID- 8136915
TI  - Determination of peptide hydrophobicity parameters by reversed-phase high
      performance liquid chromatography.
AB  - The log kw values of fourteen potential fibrinogen receptor antagonist peptides
      (RGDX) determined by reversed-phase HPLC were correlated to hydrophobic
      parameters of the amino acid side-chain log P in position X of the tetrapeptides.
      Comparing the polymer columns with LiChrosorb RP-8, the correlation coefficient
      using a polyethylene column is higher (0.94) than that for RP-8 (0.88), which
      demonstrates the importance of a homogeneous hydrophobic surface and makes this
      method very suitable for the determination of the overall hydrophobicity of
      shorter peptides. The hydrophobicity parameters log kw of the RGDX peptides (
      1.15 to 2.19) were used to investigate the influence of molecular parameters of X
      on the potency of RGDX in inhibiting platelet aggregation. The results confirm
      the importance of hydrophobicity for the contribution of X to the biological
      activity of RGDX.

PMID- 8136916
TI  - Recombinant human insulin. III. High-performance liquid chromatography and high
      performance capillary electrophoresis control in the analysis of step-by-step
      production of recombinant human insulin.
AB  - The production of recombinant human insulin consists of five main stages,
      accompanied by considerable transformation of molecules, concerning size,
      secondary structure and the presence of charged groups. The application of
      different methods, i.e., size-exclusion, ion-exchange and reversed-phase high
      performance liquid chromatography (HPLC) and high-performance capillary
      electrophoresis (HPCE) (capillary zone electrophoresis and micellar
      electrokinetic capillary chromatography), to the analysis of insulin, insulin
      related and non-insulin-related substances was studied. A combined HPLC-HPCE
      system for the step-by-step control of recombinant human insulin production
      technology is suggested. The advantages and shortcomings of these methods are
      discussed.

PMID- 8136917
TI  - Multiple-site binding interactions in metal-affinity chromatography. I.
      Equilibrium binding of engineered histidine-containing cytochromes c.
AB  - Mechanisms of protein retention in immobilized metal-affinity chromatography
      (IMAC) have been probed using a set of Saccharomyces cerevisiae iso-1-cytochrome
      c histidine variants constructed by site-directed mutagenesis. Proteins
      containing a single accessible histidine exhibit Langmuir-type isotherms with
      maximum protein binding capacities between 5 and 10% of the maximum copper
      loading and the capacity of the support to bind imidazole. A simple model that
      assumes that the copper sites are densely packed and can be blocked by protein
      adsorption yields binding constants for single-histidine proteins that are
      similar to the binding constant for free imidazole. Proteins containing multiple
      accessible histidines do not exhibit simple Langmuir-type behavior; they appear
      to interact with the support by simultaneous coordination to more than one metal
      ion, the result of which is to increase the apparent binding affinity by as much
      as a factor of 1000. The protein binding constant depends on the availability of
      copper sites: binding is significantly weaker at low surface concentrations of
      copper that presumably cannot support multiple-site interactions. The protein
      binding capacity drops to zero at copper loadings less than one-half the maximum,
      indicating that immobilized iminodiacetic acid ligands are sufficiently close
      together that two can coordinate a single copper ion, which precludes its
      interaction with a protein. Protein adsorption via multiple-site coordination has
      important consequences for the optimization of IMAC separations and the design of
      new IMAC supports.

PMID- 8136918
TI  - Small-scale multi-residue method for the determination of organochlorine and
      pyrethroid pesticides in vegetables.
AB  - A simple and inexpensive multi-residue method is described for the determination
      of organochlorine and pyrethroid pesticides in vegetables. Pesticides in
      vegetables were extracted with ethanol and partitioned into toluene. A mini
      column packed with 0.5 g of Florisil was used for further clean-up prior to gas
      chromatographic determination. The detection limits were 0.02-0.05 microgram/g
      without concentrating the extract, which are below the maximum residue limits set
      by the Singapore government. The recoveries of the pesticides from fortified
      samples were 65-97% at the 0.1 microgram/g level and 87-114% at the 0.5
      microgram/g level. The amounts of the reagents required for analysing one sample
      are only 100 ml of ethanol, 6 ml of toluene and 0.5 g of Florisil. Among fifteen
      vegetable samples collected from the Singapore local market and were analysed by
      this method, five were found to contain detectable amount of organochlorine
      pesticides. One sample contained 22 micrograms/g of endosulfan but the residue
      levels in other four samples were below 1 microgram/g.

PMID- 8136919
TI  - Comparison of high-performance liquid chromatography with radioimmunoassay for
      the determination of domoic acid in biological samples.
AB  - A reversed-phase liquid chromatographic method employing UV absorption detection
      at 242 nm was compared to a radioimmunoassay technique for the determination of
      the marine toxin, domoic acid, in several types of seafood and biological
      samples. Agreement between the two methods for spiked samples of mussels and rat
      serum was very good over a range of concentrations of 0.15-7.3 micrograms/g
      domoic acid. Also, a very good correlation was observed between the two methods
      for naturally incurred residues of domoic acid in razor clams, anchovies and crab
      meat over a concentration range of 0.6-43 micrograms/g domoic acid.

PMID- 8136920
TI  - A molecular perspective on the phylogenetic relationships of the barbeled
      minnows, historically assigned to the genus Hybopsis (Cyprinidae: Cypriniformes).
AB  - Allozyme products of 32 gene loci were compared for the North American cyprinid
      fishes Campostoma oligolepis, Cyprinella galactura, Cyprinella monacha, Erimystax
      cahni, E. dissimilis, E. insignis, E. x-punctatus, Hybopsis amblops, H. labrosa,
      H. rubriforns, H. zanema, Macrhybopsis aestivalis, M. gelida, M. meeki, Nocomis
      biguttatus, Phenacobius uranops, Platygobio gracilis, and P. storeriana. Triose
      phosphate isomerase was found to be duplicated in all species examined. Parsimony
      analysis revealed that Hybopsis sensu lato did not form a monophyletic group.
      Cyprinella monacha was found to be the sister species to members of the genus
      Cyprinella and was excluded from the genus Erimystax. A clade of four species of
      Erimystax was identified although relationships among the four species could not
      be resolved. Phenacobius was identified as the sister group to Erimystax. The
      genus Macrhybopsis was expanded to include M. aestivalis. Macrhybopsis gelida was
      identified as the sister to M. meeki and M. aestivalis as the sister to the
      former two species. The genus Platygobio was expanded to include P. storeriana.
      Hybopsis labrosa and H. zanema were found to be more closely related to members
      of the genus Hybopsis sensu stricto than to members of Cyprinella.

PMID- 8136921
TI  - Phylogenetic relationships of pocket gophers (Cratogeomys and Pappogeomys) based
      on mitochondrial DNA cytochrome b sequences.
AB  - Phylogenetic relationships among 7 of the 10 species of pocket gophers in the
      genera Pappogeomys and Cratogeomys were addressed using nucleotide sequence data
      from the entire cytochrome b gene of the mitochondrial genome (1140 base pairs).
      Results of parsimony analysis were concordant with the results of morphological
      analysis (R. J. Russell, Univ. Kans. Pub. Mus. Nat. Hist. 16: 581-776, 1968), but
      differed somewhat from the conclusions drawn from an allozymic study of these
      species (R. L. Honeycutt and S. L. Williams, J. Mammal. 63: 208-217, 1982).
      Phylogenetic analysis indicated that Cratogeomys is monophyletic, as are the two
      species groups within this genus. Estimates of levels of nucleotide sequence
      divergence between species of these genera indicated that the cytochrome b gene
      of pocket gophers may have evolved at a dramatically higher rate than in
      organisms examined previously (D. M. Irwin, T. D. Kocher, and A. C. Wilson, J.
      Mol. Evol. 32: 128-144, 1991).

PMID- 8136922
TI  - Species sampling has a major impact on phylogenetic inference.
AB  - Representative properties of gnathostome species of a rich 28S rRNA data base
      were studied through the analysis of the fluctuations they provoked in bootstrap
      proportions (BPs) of nodes of parsimonious trees. Using original programs which
      permit BP comparison between different trees, it is empirically demonstrated that
      4- to 24-species-trees are highly sensitive to species sampling: the inferences
      obtained from subsets of 4, 8, 16, or 24 species are not congruent with the whole
      set of 31 species. Study of trees obtained from exhaustively sampling all
      combinations of single species taken from each presumed monophyletic group shows
      precisely the impact of each species on the BP of each node. This procedure also
      shows that the impact of species changes within a given group on tree BPs is
      localized to its two or three neighboring nodes. The observation of differing
      impacts of species emphasizes the importance of sampling several species per
      presumed monophyletic group. It is also concluded that it is necessary to sample
      several successive outgroups and that the impact of a species on BPs depends
      mainly on the sampling context. Before undertaking extensive sequencing, the
      impact of species should be more often considered, since its effect on BPs is
      stronger than previously thought.

PMID- 8136923
TI  - Molecular phylogeny of the New World monkeys (Platyrrhini, primates).
AB  - Phylogenetic relationships among the 16 extant genera of Ceboidea (the New World
      monkeys) were examined using aligned epsilon-globin gene sequences from 19 New
      World monkeys (representing all 16 extant ceboid genera), and seven catarrhines
      (one Old World monkey and six hominoids) and tarsier as the outgroups. The
      consensus maximum parsimony tree found for these epsilon-globin sequences and the
      levels of support from parsimony and bootstrap analyses, for the clades in this
      tree, provided strong evidence for a cladistic classification with the following
      clusters. Subtribes Callitrichina (Callithrix, Cebuella), Callimiconina
      (Callimico), Leontopithecina (Leontopithecus), and Saguina (Saguinus) constitute
      subfamily Callitrichinae, and subfamilies Callitrichinae, Aotinae (Aotus),
      Saimiriinae (Saimiri), and Cebinae (Cebus) constitute family Cebidae. In turn,
      subtribes Chiropotina (Chiropotes, Cacajao) and Pitheciina (Pithecia) constitute
      tribe Pithecini, tribes Pitheciini and Callicebini (Callicebus) constitute
      subfamily Pitheciinae, tribes Atelini (Brachyteles, Lagothrix, Ateles) and
      Alouattini (Alouatta) constitute subfamily Atelinae, and subfamilies Pitheciinae
      and Atelinae constitute family Atelidae. The two families (Cebidae and Atelidae)
      constitute the Ceboidea, the only extant superfamily of infraorder Platyrrhini.
      The sister-group relationships of Brachyteles and Lagothrix, Saguinus and
      Leontopithecus, and Callimico with a Cebuella/Callithrix clade is not as well
      supported by the parsimony and bootstrap analyses. Therefore, these relationships
      are not incorporated in the proposed cladistic classification. On determining
      branch lengths for the ceboid phylogenetic tree from only the more freely
      evolving noncoding sequences at the epsilon-globin locus and taking the reference
      age of 35 million years ago (MYA) for the New World monkey-catarrhine branch
      point, we estimated the age of the atelid-cebid branch point as about 20 MYA, and
      the ages of the next branch points, those between the subfamilies in each family,
      as 19-16 MYA.

PMID- 8136924
TI  - Amazonian phylogeography: mtDNA sequence variation in arboreal echimyid rodents
      (Caviomorpha).
AB  - Patterns of evolutionary relationships among haplotype clades of sequences of the
      mitochondrial cytochrome b DNA gene are examined for five genera of arboreal
      rodents of the Caviomorph family Echimyidae from the Amazon Basin. Data are
      available for 798 bp of sequence from a total of 24 separate localities in Peru,
      Venezuela, Bolivia, and Brazil for Mesomys, Isothrix, Makalata, Dactylomys, and
      Echimys. Sequence divergence, corrected for multiple hits, is extensive, ranging
      from less than 1% for comparisons within populations of over 20% among geographic
      units within genera. Both the degree of differentiation and the geographic
      patterning of the variation suggest that more than one species composes the
      Amazonian distribution of the currently recognized Mesomys hispidus, Isothrix
      bistriata, Makalata didelphoides, and Dactylomys dactylinus. There is general
      concordance in the geographic range of haplotype clades for each of these taxa,
      and the overall level of differentiation within them is largely equivalent. These
      observations suggest that a common vicariant history underlies the respective
      diversification of each genus. However, estimated times of divergence based on
      the rate of third position transversion substitutions for the major clades within
      each genus typically range above 1 million years. Thus, allopatric isolation
      precipitating divergence must have been considerably earlier than the late
      Pleistocene forest fragmentation events commonly invoked for Amazonian biota.

PMID- 8136925
TI  - The phylogenetic utility of cytochrome b: lessons from bufonid frogs.
AB  - The mitochondrial cytochrome b gene is widely used in systematic studies to
      resolve divergences of many different ages. To investigate phylogenetic
      relationships among frogs of the large family Bufonidae, and to explore the
      utility of cytochrome b for this purpose, approximately one-third of the gene was
      sequenced from representatives of this group. Samples were chosen to represent a
      range of divergence levels within Bufonidae: (1) deep (= old), among species from
      around the world; (2) middle, among North American species; and (3) shallow (=
      young), within a single species group (the Bufo boreas group). The inferred amino
      acid sequences of cytochrome b are highly similar in these frogs although most
      pairwise comparisons of the nucleotide sequences are 15-20% different.
      Consequently insufficient information is available to generate robust
      phylogenetic hypotheses for the older divergences; silent differences are
      saturated and yet almost no informative replacement differences exist. Among the
      younger divergences, silent differences are not saturated and some resolution is
      possible. These results show that (1) the amino acid sequence of cytochrome b
      evolves differently in Bufonidae than expected based on other vertebrates (2) it
      consequently provides surprisingly little information about old divergences in
      Bufonidae, and (3) phylogenetic studies applying particular genes to new groups
      should begin with preliminary surveys of exemplar taxa representing the range of
      divergence times within the group to estimate the likely phylogenetic utility of
      that gene in that group.

PMID- 8136926
TI  - The primary structure of pancreatic ribonuclease from mole rat superspecies
      Spalax leucodon.
AB  - The primary structure of pancreatic ribonuclease of the superspecies Spalax
      leucodon has been determined. Only one difference with the previously determined
      sequence of the superspecies Spalax ehrenbergi was detected; the proline residue
      at position 42 has been replaced by alanine. Proline-42 is a well-conserved
      residue in mammalian pancreatic ribonucleases; the only other species with
      alanine at this position is the three-toed sloth. As the Muridae and the
      Spalacidae diverged 20-40 million years ago and the superspecies S. leucodon and
      S. ehrenbergi about 1-2 million years ago, and as pancreatic ribonuclease
      exhibits 24 substitutions in the line from the Muridae/Spalacidae ancestor to
      Spalax, a difference of one amino residue between the sequences of the two Spalax
      superspecies is what may be expected.

PMID- 8136927
TI  - Calcium antagonists in the treatment of ischemic heart disease: angina pectoris.

PMID- 8136928
TI  - Calcium antagonists in the treatment of ischemic heart disease: myocardial
      infarction.

PMID- 8136929
TI  - Antiarrhythmic actions of calcium antagonists.

PMID- 8136930
TI  - Calcium antagonists for the treatment of congestive heart failure.

PMID- 8136931
TI  - Calcium antagonists in the management of systemic hypertension: the impact of
      sustained-release drug-delivery systems.

PMID- 8136932
TI  - Causes of death in patients presenting to hospital with symptoms suggestive of
      acute myocardial infarction: a one-year follow-up study with autopsy results.
AB  - BACKGROUND: About 20% of patients admitted to a medical emergency room have chest
      pain or other symptoms raising suspicion of acute myocardial infarction. AIM: To
      describe the place and mode of death in such patients during 1 year of follow-up.
      PATIENTS: All patients (n = 5362) admitted to a single hospital during 21 months
      because of such symptoms. RESULTS: In all, 565 patients (11%) died. Death rate
      was directly related to the initial degree of suspicion of acute myocardial
      infarction. Of these patients, 196 (35%) died during initial hospitalization and
      only 89 (16%) died outside the hospital. The overall autopsy rate was 53%. Of the
      deaths that occurred during initial hospitalization, the majority were judged as
      cardiac, most being due to acute myocardial infarction, particularly if the
      patients died in the coronary care unit. Among patients who died after discharge
      from hospital, non-cardiac factors contributed more substantially to death,
      particularly in patients who died during rehospitalization. The cause of death
      was not established in a high proportion of patients who died outside hospital.
      CONCLUSION: The results suggest that, among patients admitted to the emergency
      room because of suspected acute myocardial infarction, causes of death other than
      a documented cardiac event become increasingly important when the interval
      between admittance to the emergency room and death increases.

PMID- 8136933
TI  - The factor dominating the determination of left ventricular filling varies during
      the first five days after acute myocardial infarction.
AB  - BACKGROUND: Left ventricular diastolic dysfunction may occur after the onset of
      acute myocardial infarction. Left ventricular diastolic filling dynamics are
      related to many factors. To evaluate the influence of left ventricular filling
      pressure on Doppler-derived left ventricular diastolic flow profiles in patients
      with acute myocardial infarction, we studied serial changes in filling during the
      first 5 days after the onset of uncomplicated acute myocardial infarction.
      METHODS: The study population consisted of 14 patients with acute myocardial
      infarction and 15 normal subjects: Doppler echocardiographic studies (left
      ventricular transmitral inflow and outflow velocity patterns) were performed on
      admission, and on the third and fifth days after infarction. Hemodynamic
      parameters were measured simultaneously using Doppler echocardiography. RESULTS:
      The E wave was lower, the A wave and A:E ratio were higher, deceleration half
      time and isometric relaxation time were prolonged, and peak left ventricular
      ejection flow velocity was lower in myocardial infarction patients than in normal
      subjects. The E wave and pulmonary capillary wedge pressure were positively
      correlated on the first and the third day (r = 0.77, P < 0.001, and r = 0.67, P <
      0.01, respectively), but not on the fifth day. The E wave and isometric
      relaxation time were negatively correlated on the fifth day (r = -0.72, P <
      0.01), but not on the first and third day. CONCLUSION: Left ventricular filling
      pressure (preload) was an important mechanism for maintaining left ventricular
      filling during the first 3 days, but the relaxation of the ventricle began to
      play a dominant role on the fifth day.

PMID- 8136934
TI  - Effect of long-term administration of probucol on triglyceride turnover in rats.
AB  - BACKGROUND: Our previous observation revealed that probucol, a well known
      cholesterol-lowering drug, can improve impaired catabolism of plasma triglyceride
      in streptozotocin-diabetic rats without reducing plasma glucose. The present
      study was conducted using Triton WR1339 and endogenously radiolabeled
      lipoproteins in order to examine the mechanisms whereby the drug can stimulate
      triglyceride removal from the circulation in rats independent of glucose
      metabolism. METHODS: The short- and long-term effects of probucol on triglyceride
      turnover were examined in rats. Male Wistar rats received a diet containing
      probucol (1%) for 2 weeks and 4 months. Triglyceride turnover was estimated in
      rats using Triton WR1339. RESULTS: After 2 weeks of probucol administration,
      triglyceride and cholesterol concentrations in plasma and in the very-low-density
      lipoprotein (VLDL) fraction were suppressed slightly but significantly in the
      probucol-administered rats compared with standard chow-fed control rats. However,
      triglyceride secretion rates were similar in the two groups. Probucol
      administered rats showed markedly suppressed triglyceride concentration in plasma
      and the VLDL fraction compared with chow-fed control rats after 4 months of
      administration. However, triglyceride secretion rate was significantly increased
      in rats given probucol. The radioisotope experiment revealed that probucol
      administered rats can remove VLDLs (lipoproteins either from probucol
      administered or control rats) from their system faster than normal rats and that
      probucol-containing VLDL can be removed from the circulation of both groups of
      rats more rapidly than normal VLDL. Therefore, probucol-administered rats as well
      as probucol-containing VLDL (lipoprotein from probucol-administered rats) are
      responsible for accelerated catabolism of VLDL-triglyceride. CONCLUSION: No
      significant differences in the lipid composition of newly-secreted VLDL particles
      between control rats and those given probucol were noted after Triton injection.
      The precise mechanism behind increased triglyceride secretion rate in rats after
      long-term administration of probucol is not known. However, we concluded from the
      present data that long-term administration of probucol results in markedly
      accelerated VLDL-triglyceride turnover without affecting lipid composition of
      newly secreted VLDL particles in normal rats.

PMID- 8136935
TI  - Restenosis following elective implantation of single Palmaz-Schatz stents in de
      novo lesions in native vessels.
AB  - BACKGROUND: Restenosis is the main limitation of long-term success after coronary
      angioplasty. Intracoronary stent implantation may reduce restenosis by producing
      a larger initial lumen and eliminating recoil. The objective of this study was to
      determine the frequency of and features associated with restenosis after elective
      single Palmaz-Schatz stent implantation in de-novo lesions in native vessels.
      METHODS: Eighty consecutive patients were studied. Angiographic follow-up was
      performed in 79 out of 80 (99%) 6.5 +/- 3.4 months after the procedure.
      Angiographic measurements were performed using an automated computerized
      quantitative angiographic analysis system. RESULTS: Restenosis (> or = 50%
      stenosis) at follow-up occurred in 26 out of 79 patients (33%). The frequency of
      complex lesion morphology was higher (50% versus 19% American College of
      Cardiology/American Heart Association classification B2; P = 0.005), the
      reference vessel diameter larger (3.0 +/- 0.5 mm versus 2.8 +/- 0.6 mm, P =
      0.049), and the lesion length longer (10.9 +/- 3.5 mm versus 8.5 +/- 3.5 mm, P =
      0.009) in the restenosis group compared with the non-restenosis group. The
      population was divided into three groups according to the reference vessel
      diameter: (1) greater than 3.0 mm (n = 27), (2) 2.5-3.0 mm (n = 29), and (3) less
      than 2.5 mm (n = 22). One patient was excluded from this subgroup analysis
      because of difficulty in determining the reference vessel diameter before the
      procedure. The restenosis rates were 52%, 37%, and 11%, respectively, for the
      three groups (P = 0.02). The relative acute gain was greater in the smaller
      vessels, (0.66 in the < 2.5 mm vessels, 0.53 in the 2.5-3.0 mm vessels, and 0.48
      in the > 3.0 mm vessels; P = 0.006). This was associated with a relative
      oversizing of the final stent balloon in the smaller vessels (balloon-to-vessel
      ratio of 1.33 in the vessels < 2.5 mm diameter, 1.16 in the 2.5-3.0 mm vessels,
      and 0.98 in the > 3.0 mm vessels; P = 0.001). CONCLUSION: The frequency of
      restenosis in single electively implanted Palmaz-Schatz stents in de-novo lesions
      in native vessels was 33%. The degree of restenosis was lower in smaller vessels,
      in which a better initial result was associated with relative oversizing of the
      final stent balloon. More aggressive dilation within the stented segment may
      result in a lower restenosis rate.

PMID- 8136936
TI  - The non-antithrombotic therapeutic potential of heparin and related heparinoids
      in cardiovascular diseases.

PMID- 8136937
TI  - Bibliography of the current world literature.

PMID- 8136938
TI  - The online journal for current clinical trials makes it onto the MEDLINE map.

PMID- 8136939
TI  - Intravesical RTNF therapy of superficial bladder cancer. A phase I study of
      recombinant tumor necrosis factor administered intravesically to patients with
      superficial bladder cancer.
AB  - OBJECTIVE: A phase I/II study was initiated in patients with refractory localized
      superficial bladder cancer to establish the tolerance and toxicity of recombinant
      tumor necrosis factor (rTNF) given intravesically. A preliminary evaluation of
      patient responses to therapy was noted; however, the small trial size precluded
      extensive statistical assessment of the data. SETTING: A large teaching hospital,
      where patients were referred for treatment of recurrent superficial bladder
      cancer. PATIENTS: A referred sample consisting of 16 patients with a primary
      diagnosis of histologically documented superficial bladder cancer (stage Ta, T1,
      TIS), refractory to at least 1 previous therapy, were entered on the study.
      Eligibility criteria Included: 1) cystoscopy in last 42 days, 2) no
      contraindications to chemotherapy, 3) life expectancy of 3 months, and 4)
      informed consent. INTERVENTION: Patients were given rTNF intravesically twice
      weekly for 4 weeks at doses ranging from 10 to 500 mcg/m2. MAIN OUTCOME MEASURES:
      Adverse effects were recorded as minimal, moderate, severe, or intolerable.
      Patient responses were measured on the basis of clinical and laboratory signs,
      symptoms, and tumor size. RESULTS: We observed no severe or intolerable
      toxicities associated with the treatment. Two patients had complete responses, 9
      had partial responses, 2 had minor responses, 1 was diagnosed with progressive
      disease, and 2 were not evaluated. No maximum tolerated dose was determined
      because rTNF was well tolerated at a maximum dose of 500 mcg/m2. CONCLUSIONS: The
      study drug rTNF was well tolerated up to a dose of 500 mcg/m2 and exhibited some
      antitumor effects against transitional cell carcinoma, but a biologically active
      dose was not determined. On the basis of this trial, further studies of
      intravesical treatment of superficial bladder cancer with rTNF appear warranted.

PMID- 8136940
TI  - The effectiveness of breast cancer screening by mammography in younger women:
      correction.

PMID- 8136941
TI  - Comparing routine versus delayed amniotomy in spontaneous first labor at term. A
      multicenter randomized trial. UK Amniotomy Group.
AB  - OBJECTIVE: To measure the effect of a policy of routine amniotomy on nulliparous
      labor. DESIGN: A multicenter randomized controlled trial. SUBJECTS: Nulliparous
      women (1463) in spontaneous labor at term with intact membranes and a single
      cephalic fetus. INTERVENTIONS: Rupturing membranes routinely early in labor or
      leaving them intact for as long as possible. MAIN OUTCOME MEASURES: Duration of
      labor, operative and instrumental delivery rates, use of analgesia, perinatal
      death, neonatal convulsions, and admission to special care. RESULTS: Median
      duration of labor was 8.4 hours in the early rupture group and 9.4 hours in the
      late group. No clear trend for this difference emerged at any particular cervical
      dilatation at randomization. We found no difference in cesarean section, typical
      odds ratio (OR) 1.1 (95% CI, 0.65 to 1.8); operative vaginal delivery, OR 1.1
      (95% CI, 0.83 to 1.5); use of epidural/spinal, OR 0.92 (95% CI, 0.72 to 1.2); use
      of pethidine, OR 1.0 (95% CI, 0.79 to 1.4); either method of analgesia, OR 0.96
      (95% CI, 0.68 to 1.3); blood transfusion, OR 0.71 (95% CI, 0.28 to 1.8. We found
      no effect on fetal intubation, OR 1.40 (95% CI, 0.78 to 2.5), or on admission to
      special care, OR 1.28 (95% CI, 0.65 to 2.5). One fetus in the early amniotomy
      group had care, Or 1.28 (95% CI, 0.65 to 2.5). One fetus in the early amniotomy
      group had neonatal convulsions, but there were no perinatal deaths. CONCLUSIONS:
      Beyond a modest shortening of labor, a policy of routine amniotomy has little
      effect on important outcomes and should not be recommended.

PMID- 8136942
TI  - The use of interleukin-6 to generate tumor-infiltrating lymphocytes with enhanced
      in vivo antitumor activity.
AB  - Tumor-infiltrating lymphocytes (TIL) are cytotoxic T cells isolated from solid
      tumors and expanded in vitro in recombinant interleukin-2 (rIL-2). TIL have
      antitumor effects in murine models and in some patients with melanoma. In an
      effort to generate murine TIL with enhanced in vivo therapeutic efficacy, viable
      tumor cells were coinjected with a collagen matrix plus recombinant human IL-6
      (rIL-6) subcutaneously into syngeneic mice to achieve sustained local
      concentrations of rIL-6 at the tumor site from which TIL were derived. In five
      separate experiments, single cell suspensions of tumors were admixed with either
      (a) Hanks' balanced salt solution (HBSS), (b) 2% (20 mg/ml) collagen matrix only,
      (c) 250 micrograms rIL-6 only, or (d) 250 micrograms rIL-6 in a 2% collagen
      matrix (prolonged release) before subcutaneous inoculation. These tumors were
      subsequently resected and TIL were isolated and expanded in vitro. TIL generated
      from tumors admixed with matrix plus rIL-6 were significantly more effective than
      TIL expanded from tumors admixed with HBSS (four of five experiments), TIL from
      tumors admixed with matrix only (five of five experiments), and TIL from tumors
      admixed with rIL-6 only (three of four experiments) in an established tumor
      treatment model. In no experiment was any other TIL culture superior to TIL grown
      from tumors augmented with collagen matrix plus rIL-6. These results suggest that
      strategies designed to increase the local concentrations of cytokines at tumor
      sites may lead to the generation of more potent TIL for clinical administration.

PMID- 8136943
TI  - Interleukin-4 affects phenotype and proliferative response of peripheral blood
      lymphocytes from glioblastoma patients after specific or nonspecific in vitro
      stimulation.
AB  - Immunosuppressive events are often observed in glioblastoma-bearing patients. We
      tested the response of circulating lymphocytes from glioblastoma patients to low
      concentrations of interleukin (IL)-4 and IL-2 after lectin activation or specific
      in vitro stimulation by autologous tumor cells. In the presence of IL-2, IL-4 up
      regulates the proliferation rate of phytohemagglutinin (PHA)-P-stimulated
      glioblastoma patients' peripheral blood lymphocytes (PBL)s. Allogeneically- and
      syngeneically-stimulated PBLs of these patients present an increased
      proliferation rate in the presence of IL-4. This specifically stimulated
      lymphocyte population presents a very low proportion of CD8+ cells. This
      proportion is slightly increased in the presence of IL-4. Our results indicate
      that the glioblastoma cell-imposed inhibition on T-cells can be partly overcome
      by low concentrations of IL-4 during in vitro stimulation. Our experiments also
      demonstrate that glioblastoma-bearing patients' PBLs constitute a good model in
      which to study the effects of IL-4.

PMID- 8136944
TI  - Production of interleukin-2 by EL4 tumor cells induces natural killer cell- and T
      cell-mediated immunity.
AB  - Systemic administration of recombinant interleukin (rIL)-2 to cancer patients has
      met with limited clinical success since, despite significant antitumor effects,
      its use is associated with severe toxicity. Local production of IL-2 by IL-2 gene
      transfected tumor cells in murine model systems has been reported to induce
      specific immunity--devoid of toxicity--to the parental non-IL-2-producing tumor
      cells. We now report enhanced resistance in nonimmunized mice to murine EL4
      thymoma cells, producing murine IL-2 following gene transfer (EL4pIL-2). This
      effect is mediated by activated natural killer (NK) cells, since we observed the
      same effect in nude mice but not in NK-depleted mice. Additionally, in mice
      repeatedly vaccinated with irradiated EL4pIL-2 cells, we observed immunity to
      challenge with a tumorigenic dose of EL4 cells transfected with a control vector,
      EL4p. EL4-specific cytotoxic T-lymphocytes (CTLs) were detected in these mice.
      Mice vaccinated with irradiated EL4p cells were less protected against challenge
      with a tumorigenic dose of EL4p cells. This study indicates that although some IL
      2-producing autologous tumor cells elicit NK-mediated responses and not CTL
      responses upon inoculation, tumor-specific CTL responses are generated upon
      repeated vaccinations with these cells. This strategy has potential application
      for treating a wide variety of cancer patients with autologous IL-2 producing
      tumor cells.

PMID- 8136945
TI  - Effects of tumor necrosis factor and dexamethasone on the regulation of
      interferon-gamma induction by monophosphoryl lipid A.
AB  - Monophosphoryl lipid A (MLA), derived from lipopolysaccharide (LPS) of Salmonella
      minnesota strain R595, induced rapid accumulation of interferon (IFN)-gamma in
      mice. Tumor necrosis factor (TNF)-alpha appeared to be a cofactor for IFN-gamma
      induction by MLA. With low doses of MLA (< 5 micrograms), IFN-gamma induction was
      dependent upon exogenous TNF-alpha administered either in advance of or with MLA.
      A 25 micrograms dose of MLA induced significant IFN-gamma accumulation in the
      absence of exogenous TNF-alpha. In this case, endogenous TNF-alpha appeared to be
      a cofactor in the response, since suppression of TNF-alpha production with
      dexamethasone inhibited IFN-gamma induction, and this inhibition was overcome by
      administration of exogenous TNF-alpha with MLA. Treatment of animals with MLA
      tolerized them against LPS. Tolerant animals did not produce IFN-gamma when
      challenged with LPS, and this tolerance was not abrogated by supplementing mice
      with exogenous TNF-alpha during the challenge. Although dexamethasone inhibited
      IFN-gamma induction by MLA, it did not inhibit tolerance induction by MLA.

PMID- 8136946
TI  - Phase Ib trial of the effect of peritumoral and intranodal injections of
      interleukin-2 in patients with advanced squamous cell carcinoma of the head and
      neck: an Eastern Cooperative Oncology Group trial.
AB  - Thirty-six patients with unresectable squamous cell carcinoma of the head and
      neck were entered into a phase Ib trial evaluating the toxicity, maximally
      tolerated dose (MTD), and immunomodulating effects of locally administered
      interleukin-2 (IL-2). Patients received daily IL-2 injected perilesionally in
      divided doses in each of four quadrants and bilaterally into the superior jugular
      lymph nodes. The dose of IL-2 began at 200 U/day and was escalated to 4 x 10(6)
      U/day in groups of six patients. Overall, regionally administered IL-2 was well
      tolerated. The most frequently encountered toxicities were fever, hepatotoxicity,
      and hypotension. Dose-limiting toxicity was encountered at 4 x 10(6) U. Of the 36
      patients treated, 2 partial responses were noted at 2,000 and 4 x 10(6) U. We
      conclude that regionally administered IL-2 is well tolerated in patients with
      head and neck cancer and that the MTD is 2 x 10(6) U/day, similar to what has
      been reported with systemically administered IL-2. Although the overall response
      rate was low, it may be improved with prolonged administration of IL-2 or by
      combining it with other biologic or cytotoxic agents.

PMID- 8136947
TI  - A comparative study of intravenous versus intralymphatic interleukin-2, with
      assessment of effects of interleukin-2 on both peripheral blood and thoracic-duct
      lymph.
AB  - Recombinant human interleukin-2 (IL-2) was administered by the intravenous (i.v.)
      or intralymphatic (i.l.) route to 14 patients with advanced malignancy. IL-2 was
      given in doses of 600,000 IU/kg or 1,050,000 IU/kg daily x 5. Thoracic duct (TD)
      catheters were placed, and both TD lymphocytes (TDL) and peripheral blood
      lymphocytes (PBL) were studied. Five of eight patients at the 600,000 IU/kg dose
      experienced grade III toxicity as did five of six patients at the 1,050,000 IU/kg
      dose. Two episodes of grade IV toxicity were seen at the higher dose. The i.l.
      and i.v. routes had a similar toxicity profile excepting lymphangitis/pedal
      infection, seen only with i.l. administration. One partial response was seen in a
      patient with renal cell carcinoma. Lymphopenia was seen early in therapy, with
      lymphocytosis by day 6. Lymphoid yield of the TD catheter fell early in therapy,
      then increased over baseline by the end of treatment. Intralymphatic
      administration resulted in a prolonged serum t1/2 and lower serum levels than did
      i.v. administration, but resulted in higher TD levels. Antibodies against IL-2
      were ubiquitous but had no clear effects. Lymphocyte trafficking studies
      suggested that IL-2 affected lymphocyte redistribution to liver, spleen, bone
      marrow, and lymph nodes. NK activity and phenotype and LAK activity increased in
      response to IL-2, with no advantage for TDL. Tumor necrosis factor-alpha and
      gamma-interferon levels increased sporadically with treatment. The i.l. route
      offered no advantage over the i.v. route, and TDL offered no advantage over PBL.

PMID- 8136948
TI  - Phase II studies of recombinant human interleukin-4 in advanced renal cancer and
      malignant melanoma.
AB  - Interleukin (IL-4) is a pluripotent cytokine that stimulates proliferation of
      activated T-cells and has antineoplastic activity against human renal tumors in
      animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20
      micrograms/kg, with dose-limiting toxicities consisting of fever, fluid
      retention, nasal congestion, and mucositis. We report the results of two separate
      Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19
      patients with advanced renal cancer. IL-4 was administered intravenously every 8
      h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27
      patients were treated at a dose of 800 micrograms/m2, but after three of these
      patients developed cardiac toxicities, the dose was decreased to 600
      micrograms/m2. One complete response occurred in a patient with metastatic
      melanoma (duration > or = 30 months). No responses were seen among the patients
      with renal cancer. The most frequent side effects were fever, nausea, malaise,
      nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were
      also common. Hypotension was infrequent, but transient weight gain due to fluid
      retention was common. The major life-threatening toxicities were cardiac and
      gastrointestinal. Suspected cardiac ischemia was observed in two patients,
      pericarditis in one, and arrhythmias in two. Three patients had major upper
      gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4,
      when given as a single agent on this schedule at maximum tolerated dose, does not
      possess meaningful activity in renal cancer or melanoma.

PMID- 8136949
TI  - Interleukin-2 gene transfer into murine neuroblastoma decreases tumorigenicity
      and enhances systemic immunity causing regression of preestablished
      retroperitoneal tumors.
AB  - Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector LIL-2SN
      in order to examine the influence of localized interleukin (IL)-2 production on
      the immune response against a low major histocompatibility complex (MHC) class I,
      class II-negative, and intercellular adhesion molecule (ICAM)-1-negative tumor.
      Two neomycin-resistant (neo R) clones, N-2a/IL-2/L (2.5 +/- 0.4 U/ml/10(6)
      cells/24 h) and N-2a/IL-2/H (44.6 +/- 8.8 U/ml), were studied as representative
      low and high IL-2 producers, respectively. Using a recently developed
      retroperitoneal (r.p.) model for implantation of neuroblastoma in its natural
      site, we demonstrated that production of IL-2 by neuro-2a reduces its
      tumorigenicity in a dose-dependent fashion. T-cell, but not natural killer (NK)
      cell, depletion significantly increased tumor induced mortality in syngeneic A/J
      mice. Mice genetically devoid of T-cells (C.B-17 scid/scid) also experienced a
      significant increase in mortality rates. This indicates that the antitumor effect
      of locally secreted IL-2 is mediated primarily through activation of T-cells.
      Immunization of mice with irradiated N-2a/IL-2/H cells resulted in protection
      when challenged at a later date with unmodified neuro-2a cells. Depletion of
      CD8+, but not CD4+, T-cells prior to vaccination abrogated the protective effect,
      indicating that the priming phase of the immune response is CD8+ T-cell
      dependent. Mice with established r.p. tumors were vaccinated with N-2a/IL-2/H,
      which significantly prolonged their survival compared to unimmunized controls and
      to mice immunized with non-IL-2-producing neuro-2a cells. Because of the
      similarities of this model with the human tumor, our studies indicate that IL-2
      transduced neuroblastoma cells may be effective in generating systemic immunity
      leading to eradication of minimal residual disease.

PMID- 8136950
TI  - [Stress in nursing].

PMID- 8136951
TI  - [Stress and burnout].

PMID- 8136952
TI  - [Stress and how to master it].

PMID- 8136953
TI  - [A profession in a dramatic triangle].

PMID- 8136954
TI  - [Professionals and laymen].

PMID- 8136956
TI  - [How often does the wash water have to be changed?].

PMID- 8136955
TI  - [More than meadows, woods and mountains: The Allgau].

PMID- 8136957
TI  - [Responsibility at any price. Problems of self concept in the work place and
      psychosocial repercussions].

PMID- 8136958
TI  - [Theories of suicide].

PMID- 8136959
TI  - [Recognizing the danger of suicide--a nursing concern].

PMID- 8136960
TI  - [Crisis intervention with suicidal patients].

PMID- 8136962
TI  - [Suicide in psychiatry].

PMID- 8136961
TI  - [Suicide wishes in severely ill patients].

PMID- 8136963
TI  - [I am dying, therefore I am. Reread: Laying hands on oneself--Jean Amery's
      discourse on suicide].

PMID- 8136964
TI  - [Suicide in the aged].

PMID- 8136965
TI  - [Suicide and suicidal behavior in children and adolescents].

PMID- 8136966
TI  - [Legal problems in connection with suicide and attempted suicide].

PMID- 8136967
TI  - [Suicide and freedom].

PMID- 8136968
TI  - [Psychosocial support in the acute hospital between curative treatment and
      psychotherapy].

PMID- 8136969
TI  - [Psychosocial support during hospital after-care. Needs and concepts].

PMID- 8136970
TI  - [Psychosocial support in pediatrics. Successes and problems of the model
      children].

PMID- 8136971
TI  - [Experience of meaning. Chances and limits of patients and their helpers].

PMID- 8136972
TI  - [Psychosocial support as a health political concern in the community. Progress in
      spite of cost reductions].

PMID- 8136973
TI  - [Psychosocial support as a family-centered effort. The family is given help].

PMID- 8136974
TI  - [Support of cancer patients. Concepts, experiences visions].

PMID- 8136975
TI  - [How far did we get? A position sketch of psychosocial oncology].

PMID- 8136977
TI  - [The quality of life of cancer patients. Single fates and statistics].

PMID- 8136976
TI  - [Self-help and self-help groups. Self-help and outside help in balance].

PMID- 8136978
TI  - [Phases in disease and therapy. An attempt at understanding].

PMID- 8136979
TI  - [Intravenous injection of opiates and use of defibrillators. Competencies of the
      specialized nursing personnel in anesthesia and intensive medicine].

PMID- 8136980
TI  - [The first day of the rest of my life. My fall from reality and the walk on the
      edge between being hurt and finding support].

PMID- 8136981
TI  - [Supportive care and treatment of cancer patients].

PMID- 8136982
TI  - [Continuing nursing education in oncology].

PMID- 8136983
TI  - [Patient oriented and phase adopted patient information in oncology].

PMID- 8136984
TI  - ["Sometimes I feel like a prisoner". Reversed isolation of patients during
      cytostatic therapy].

PMID- 8136985
TI  - [Pain therapy in tumor patients].

PMID- 8136986
TI  - [Nutritional therapy in cancer patients].

PMID- 8136987
TI  - [Occupational therapy in chronic obstructive pulmonary disease].

PMID- 8136988
TI  - [Domiciliary care in COPD].

PMID- 8136989
TI  - [Noninvasive mechanical ventilation].

PMID- 8136990
TI  - [Respiratory rehabilitation].

PMID- 8136991
TI  - [Respiratory rehabilitation: yes or no?].

PMID- 8136992
TI  - [Education of the patient and his family].

PMID- 8136993
TI  - [Nutrition in chronic respiratory disease].

PMID- 8136994
TI  - [The psychosocial aspects of chronic respiratory disease].

PMID- 8136995
TI  - [Quality of life: its application to respiratory rehabilitation].

PMID- 8136996
TI  - [Respiratory physiotherapy].

PMID- 8136997
TI  - [Exercise training as a therapeutic technic in patients with chronic obstructive
      pulmonary disease (COPD)].

PMID- 8136998
TI  - [Ventilatory muscle training].

PMID- 8136999
TI  - The neurobiology of primate vision.
AB  - Studies of the visual system of the primate have taken two directions. One group
      of neurobiologists have studied the oculomotor system, while an entirely separate
      group have analysed sensory processing in the retinogeniculo-cortical circuits.
      However, the versatility and adaptability of the primate visual system is only
      possible because sensory and oculomotor processing are highly integrated. More
      than any other species, primates have exploited the advantages of extensive and
      coordinated binocular eye movements to improve their visuomotor performance. This
      chapter describes the basic apparatus of primate vision. The integrated nature of
      visuomotor function is illustrated by two examples: smooth pursuit eye movements
      and stereovision. Both of these tasks require huge amounts of sensory processing
      in many different visual centres and, simultaneously, very precise control of
      binocular eye position. These examples illustrate the difficulty and
      artificiality of assigning unique functions to any component part of the system.
      Each part of the visual system, from the retina through the brain to the
      oculomotoneurones that drive the eye muscles, is involved in many different
      functions. This integration within the system raises the problem of how we
      represent and recognize our visual world in the brain. The traditional view from
      sensory psychology is that single nerve cells in the visual cortex signal
      significant percepts. As this chapter shows, the activity of single cortical
      neurones is influenced by multiple factors, including the qualities of the visual
      stimulus, the position of the eyes, and the attention being paid to the stimulus.
      Thus, the activity of single neurones is an ambiguous indicator of both
      perceptual and motor events. Only the collective action of many nerve cells, it
      seems, represents unique percepts and actions. Given this indivisibility of
      function, patients with localized brain lesions will invariably present with
      multiple visuomotor deficits.

PMID- 8137000
TI  - Residual vision following geniculostriate lesions.

PMID- 8137001
TI  - Visual illusions and hallucinations.
AB  - Visual illusions and hallucinations may accompany a wide variety of disorders
      with many different aetiologies; therefore, they are non-specific phenomena.
      Lesions in the visual pathway may be associated with visual misperceptions. In
      these cases more exact information about the misperceptions--whether they are
      monocular or binocular, present in the whole visual field or a hemifield--may
      contribute to diagnostic accuracy and to a more comprehensive understanding of
      the patient and his state of mind. Illusions such as perseveration, monocular
      diplopia and polyopia, and dysmorphopsia may also occur in healthy individuals,
      but they are found most often in patients with epilepsy, migraine and stroke.
      These phenomena do not permit exact localization and definition of an aetiology,
      but lesions in the occipital and occipitotemporal regions near the visual pathway
      are involved in most cases. Hallucinations always represent a pathological form
      of perception. They are classified as unformed (photopsias) or formed (complex).
      Photopsias may be described in terms of colour, shape and brightness. Their wide
      variety makes it difficult, if not impossible, to arrive at an exact description
      of their aetiology, but it is possible to define their anatomical origin in some
      cases. Complex hallucinations suggest an occipitotemporal locus. Whether they
      appear in the whole visual field or in the hemifield may prove decisive in
      determining pathogenesis. A number of characteristics permit a rough
      classification of these phenomena. Complex hallucinations accompany physical
      illness and are susceptible to psychodynamic interpretation.

PMID- 8137002
TI  - The neural basis of mental imagery.
AB  - Mental visual images can be employed for widely different tasks and they can
      depict widely different kinds of visual entities. There is evidence that the
      context and content of mental visual images matter for the determination of their
      neural basis. Single case studies demonstrate that there are at least five kinds
      of visual entities whose imagery can be affected independently from each other:
      shapes of objects, colours of objects, faces, letters and spatial relationships.

PMID- 8137003
TI  - Acquired deficiencies of human colour vision.

PMID- 8137004
TI  - Object agnosias.

PMID- 8137005
TI  - Recent developments in the neuropsychology and physiology of face processing.
AB  - This chapter will review neuropsychological studies of face processing defects.
      Recent research in this field has been dominated by evidence of preserved face
      processing in patients who are unaware of these abilities. This phenomenon is
      referred to as covert recognition and forms a main focus for this review. The
      second part of the chapter reviews the advances in physiological studies of the
      brain mechanisms underlying face processing. The relationship between normal
      perception of faces and information processing at the single cell level is
      considered. Finally the chapter discusses how the physiological findings relate
      to the pathology of face processing.

PMID- 8137006
TI  - Disorders of visual attention.

PMID- 8137007
TI  - 'Balint's syndrome' and associated visuospatial disorders.
AB  - There are several objections to the need for the designation 'Balint's syndrome'.
      The full syndrome is generally associated with a wide variety of behavioural
      disturbances outside Balint's original triad that may confound the interpretation
      of their supposed defect. It embeds itself in the hemineglect syndrome, violating
      the principle of autonomy for a syndrome. Individual components of the triad,
      particularly simultanagnosia, may represent relatively broad categories that
      subsume other combinations of defects of widely different degrees of severity.
      The diagnosis fails to predict a consistent site of anatomical impairment, and
      the main proposed mechanism is not sound. Our experience with a registry of
      patients with focal brain lesions and well-documented behavioural impairments
      (Palca, 1990), now numbering over 1500 individuals, tends to support these
      generalizations.

PMID- 8137008
TI  - Visuomotor coordination as a dissociable visual function: experimental and
      clinical evidence.

PMID- 8137009
TI  - Visual and visual perceptual disorders in neurodegenerative diseases.
AB  - Optic neuropathy is reported to occur in 10-30% of patients, while retinopathy is
      characteristic of type III OPCA. The use of visual and visual
      electrophysiological tests in early diagnosis and classification is promising.
      The relationship between visual impairment and other manifestations of these
      diseases has not been explored.

PMID- 8137010
TI  - Abdominal pain.
AB  - Abdominal pain remains a common complaint in children and adolescents and
      accounts for a frequent number of visits to pediatricians as well as
      gastroenterologists. A thorough understanding of the neuroanatomy and
      neurophysiology of the abdomen and its contents is immensely important in
      understanding the origins of abdominal pain and formulating a limited
      differential diagnosis for the patient presenting with abdominal pain. With this
      as fundamental background, and the important clues provided by a thorough history
      and physical examination, a rapid and accurate diagnosis for the pediatric
      patient presenting with either acute, subacute, or chronic abdominal pain can be
      in most instances reasonably ascertained. Subsequently, specific studies for
      confirmation can then be performed and appropriate treatment implemented. The
      tremendous advancement in the field of gastroenterology provided by the continued
      development of endoscopic procedures has allowed for precise identification of
      many GI disorders. Endoscopy in concert with radiology procedures can be used
      effectively now to adequately establish a diagnosis in almost all patients
      presenting with abdominal pain.

PMID- 8137011
TI  - Introduction to pediatric esophagogastroduodenoscopy and enteroscopy.
AB  - Pediatric esophagogastroduodenoscopy is now an integral part of the practice of
      pediatric gastroenterology. Children are not just small adults. The differing
      clinical indications, approaches to patient preparation, sedation, and
      complications are discussed in this article.

PMID- 8137012
TI  - Colonoscopy and therapeutic intervention in infants and children.
AB  - Colonoscopy is an established procedure for the investigation of large bowel and
      terminal ileal disease in infants and children. Specific indications vary with
      the child's age. Preparation and sedation of the pediatric patient and
      colonoscopy techniques must be tailored to the age and physical stature of the
      patient.

PMID- 8137013
TI  - Endoscopic retrograde cholangiopancreatography in children.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is playing an increasingly
      important role in the evaluation and treatment of children with disorders of the
      pancreas and biliary tree. In this article the technique, indications, and
      complications of diagnostic and therapeutic ERCP in children are reviewed. ERCP,
      when used properly, improves the ability of the clinician to diagnose and treat.
      Therapeutic ERCP reduces the need for surgery, and preoperative ERCP provides
      surgeons with a "road map" when surgery is required.

PMID- 8137014
TI  - Percutaneous endoscopic gastrostomy placement in children.
AB  - Percutaneous endoscopic placement of gastrostomy tubes in children has become
      common since its introduction in 1980. Indications and technique for placement,
      as well as complications in children are discussed. A summary of the recent
      experience with percutaneous endoscopic jejunostomy is also provided.

PMID- 8137015
TI  - Mucosal biopsy.
AB  - Intestinal mucosal biopsy has become an invaluable tool for the evaluation of
      children with abdominal complaints. Multiple techniques and biopsy instruments
      have each been developed with advantages and limitations. Physicians caring for
      infants and children must be familiar with indications for tissue sampling,
      timing of the biopsies, and interpretations of biopsy specimens.

PMID- 8137016
TI  - Nonsurgical treatments for portal hypertension in children.
AB  - The nonsurgical management of portal hypertension in infants and children has
      undergone dramatic changes with the advent of endoscopic injection sclerotherapy
      and variceal ligation. Additional newer therapeutic interventions include
      radiographic transhepatic obliteration of vessels and angiographic portosystemic
      shunts. Adjunctive drug therapy is helpful in selected cases. Physicians managing
      infants and children with varices must understand the nature of portal
      hypertension in younger patients and the limitations of the therapeutic
      modalities.

PMID- 8137017
TI  - Peptic ulcer disease in children.
AB  - Although much of the understanding of the pathogenesis of ulcer disease is
      derived from data studying adults, there are certain manifestations and
      presentations that differentiate ulcers in children from those seen in adults.
      Therapy is aimed at reducing acid or improving mucosal defense. The recent
      recognition of the association of Helicobacter pylori with acid peptic disease
      has added to our understanding of the disease process and opened new avenues of
      therapy.

PMID- 8137018
TI  - Inflammatory bowel disease in children and adolescents.
AB  - Twenty-five percent of the patients with inflammatory bowel disease develop
      symptoms within the first two decades of life. The approach to children with
      these chronic illnesses involves an understanding of the medical, nutritional,
      and psychological issues of maturing children and adolescents. Children with
      Crohn's disease and ulcerative colitis have different clinical presentations than
      adult patients. The physician must decide when to perform diagnostic procedures
      and which management options will be successful.

PMID- 8137019
TI  - Gastroesophageal reflux in children. Clinical presentation and diagnostic
      evaluation.
AB  - Gastroesophageal reflux in infants and children is common. It is distinguished
      from the disorder in the adult population by the large number of thriving infants
      with functional reflux and by the large proportion of older infants and children
      with secondary pathologic reflux, in whom vomiting and reflux are symptoms of
      another condition. Evaluation of the child with suspected reflux starts with a
      thorough history and physical examination. Diagnostic testing must be tailored to
      the suspected diagnosis.

PMID- 8137020
TI  - Gastrointestinal bleeding in children.
AB  - This article reviews the differential diagnosis, diagnostic approach, and
      selected therapeutic interventions employed in children with gastrointestinal
      bleeding. The focus of this article is on the presenting features of various
      bleeding lesions and an organized and efficient use of diagnostic and therapeutic
      modalities.

PMID- 8137021
TI  - Foreign bodies, bezoars, and caustic ingestion.
AB  - Children, particularly infants, frequently put objects into their mouths, and
      occasionally these objects are swallowed. Fortunately, most foreign bodies are
      harmless and will pass spontaneously through the gastrointestinal tract. Some
      foreign bodies such as the rare bezoar or caustic substances, provide unique
      clinical challenges. This article provides guidelines for the management of such
      problems.

PMID- 8137022
TI  - Is it safe to drive with an automatic implantable cardioverter defibrillator or a
      history of recurrent symptomatic ventricular arrhythmias?

PMID- 8137023
TI  - The value of exercise in preventing coronary atherosclerotic heart disease.
AB  - This article has related the value of exercise in preventing coronary
      atherosclerotic heart disease. This disease is multifactorial in origin and is
      prevented primarily by modifying risk factors. Proper exercise does not imply
      high-level physical fitness or conditioning; it may be occupational or leisure
      time activity, recreational activity, or regular aerobic exercise three to four
      times weekly for 30-60 minutes at a time, as recommended by the American Heart
      Association. Such physical activity can be performed by most people, even the
      disabled, and certainly, modifying risk factors is more cost effective and more
      enjoyable than coronary heart disease itself. Therefore, physical activity must
      be emphasized in the management of coronary atherosclerotic heart disease.

PMID- 8137024
TI  - Cardiac auscultation: opening snaps, systolic clicks, and ejection sounds.

PMID- 8137025
TI  - Indications for coronary arteriography.

PMID- 8137026
TI  - New interventional techniques for coronary revascularization.

PMID- 8137027
TI  - Management of hypertrophic cardiomyopathy.

PMID- 8137028
TI  - Use of warfarin (coumarin).

PMID- 8137029
TI  - Recognition and management of acute aortic regurgitation.

PMID- 8137030
TI  - Recognition and management of deep vein thrombosis.

PMID- 8137031
TI  - Patent foramen ovale: a new risk factor for ischemic stroke.

PMID- 8137032
TI  - Relationship of emotional stress to the heart.

PMID- 8137033
TI  - Vasovagal syncope: current concepts in diagnosis and treatment.
AB  - Vasovagally mediated episodes of hypotension and bradycardia are thought to be
      common causes of recurrent unexplained syncope. Head-up tilt table testing,
      either alone or with a graded-dose infusion of isoproterenol, is a useful
      diagnostic test for identifying persons who are susceptible to vasovagal syncope.
      In addition to its diagnostic ability, tilt table testing may provide a means to
      assess the efficacy of preventive pharmacotherapy for syncope. Further study of
      tilt table testing is needed to increase understanding of vasovagal syncope and
      to better define the test's role in the diagnosis and management of this
      condition.

PMID- 8137034
TI  - Digitalis and the Na+,K(+)-ATPase.
AB  - Recent clinical, physiological, biochemical, and molecular biology studies
      strongly suggest that digitalis glycosides function in a complex manner through
      differential binding to and inactivation of multiple distinct Na+,K(+)-ATPase
      isoforms that are differentially expressed and regulated throughout the
      cardiovascular system. The alpha 1 isoform predominates in the ventricular:
      myocardium, whereas the alpha 2 and alpha 3 isoforms may localize to the
      conducting system structures. The peripheral vasculature also potentially
      expresses three digitalis receptors, as do neurons in the central nervous system.
      It is likely that similar heterogeneity exists in the autonomic nervous system as
      well as in the cardiopulmonary baroreceptor structures. Therefore, differential
      regulation of these isoforms, by either genetic predisposition or hormones, could
      dissociate contractile from conduction function and play a role in determining
      the degree, if any, of therapeutic response to digitalis glycosides. Similarly,
      genetic polymorphism of the alpha subunits has been observed in humans and rats
      and may play an important functional role in the ion transport function in a
      strain of hypertensive rats. Genetic differences in the regulation or structure
      and function of each isoform could confer allele-specific functional and
      pharmacological features such as predisposition to digitalis toxicity.
      Alterations in the degree and type of Na+,K(+)-ATPase isoforms expressed during
      cardiac hypertrophy and cardiac development may mediate increases or decreases in
      cardiac sensitivity to digitalis glycosides. This unexpected complexity of the
      digitalis receptor raises new questions about the role of digitalis glycosides in
      the treatment of congestive heart failure.

PMID- 8137035
TI  - Combination therapy with HMG CoA reductase inhibitors and gemfibrozil: practical
      or perilous?

PMID- 8137036
TI  - Side effects of HMG CoA reductase inhibitors.

PMID- 8137037
TI  - Treatment of hypercholesterolemia in patients with known coronary artery disease.

PMID- 8137038
TI  - Vertebrobasilar disease: should we continue the double standard of managing
      patients with brain ischemia?

PMID- 8137039
TI  - Recognition and significance of amaurosis fugax.

PMID- 8137040
TI  - How to monitor the dosage of warfarin.
AB  - To use and monitor warfarin therapy appropriately, the clinician must understand
      the pharmacodynamics and time profile of this agent and how the clotting cascade
      and coagulation inhibitor system are affected early in therapy. The redefined
      guidelines for PT monitoring require that the INR be used to monitor all patients
      receiving warfarin. Safety also requires that patients be monitored closely and
      that both the clinician and the patient be alert to potentially interacting
      variables. With long-term therapy, one must continually reassess the risk-to
      benefit ratio of continuing therapy, changing the level of anticoagulation
      intensity, or discontinuing therapy. Finally, it is particularly important that
      patients understand the potential risks and benefits of anticoagulation therapy
      and how to monitor themselves. Patients should be encouraged to contact the
      appropriate clinician immediately with any questions that may influence the
      continued safe and effective use of warfarin.

PMID- 8137041
TI  - Indications and value of the use of captopril after myocardial infarction.

PMID- 8137042
TI  - Early recognition and treatment of acute ischemic stroke.

PMID- 8137043
TI  - Quinidine: its value and danger.

PMID- 8137044
TI  - Thyrotoxicosis and cardiac disease.

PMID- 8137045
TI  - Patient adherence: a 'risk factor' for cardiovascular disease.
AB  - Adherence to cardiovascular treatment regimen is a major problem that limits the
      potential success of therapeutic advances. Considerable understanding of this
      issue has been gained in recent years, and improved approaches are available for
      the practitioner to improve patient adherence.

PMID- 8137046
TI  - Neurological manifestations of migraine.

PMID- 8137047
TI  - Buerger's disease.

PMID- 8137048
TI  - Oxidative phosphorylation diseases and stroke.

PMID- 8137049
TI  - Detection, evaluation, and treatment of hypertension: JNC-5 (Joint National
      Committee on Detection, Evaluation, and Treatment of High Blood Pressure)

PMID- 8137050
TI  - To anticoagulate or not to anticoagulate? That is no longer the question.

PMID- 8137051
TI  - Detection of right ventricular myocardial infarction associated with inferior
      myocardial infarction from the standard 12-lead electrocardiogram.

PMID- 8137052
TI  - The correlation of clinical findings and severity of aortic insufficiency: Hill's
      sign.

PMID- 8137053
TI  - Procainamide: a perspective on its value and danger.
AB  - Procainamide remains one of the most widely used antiarrhythmic agents in
      clinical practice. Currently, it is widely used alone or in combination with
      class I agents (eg, mexiletine or tocainide) to prevent recurrent ventricular
      tachycardia or symptomatic nonsustained ventricular tachycardia. Procainamide is
      also used for short-term treatment of ventricular tachycardia and a variety of
      supraventricular tachycardias, primarily atrial flutter and atrial fibrillation.
      Long-term procainamide therapy is limited by a number of systemic side effects,
      primarily lupus-like syndrome, gastrointestinal disturbances, and autoimmune
      blood dyscrasias. Procainamide levels can be useful in initial dose titrations;
      however, QRS and QT interval measurements help prevent drug toxicity. It is
      recommended that patients being started on antiarrhythmic therapy with
      procainamide be admitted to the hospital for monitoring to ensure that their QT
      interval is not excessively prolonged.

PMID- 8137054
TI  - Neurological presentations of atrial myxoma.

PMID- 8137055
TI  - Hemochromatosis and the heart.

PMID- 8137056
TI  - Long-term management of prosthetic valves.

PMID- 8137057
TI  - Cerebral percutaneous transluminal angioplasty.

PMID- 8137058
TI  - Need for treatment of elevated plasma fibrinogen levels in cerebrovascular
      disease.

PMID- 8137059
TI  - Use, value, and toxicity of amiodarone.

PMID- 8137060
TI  - Exercise: how much is enough, and how much is too much?

PMID- 8137061
TI  - Indications for antithrombotic therapy after myocardial infarction.
AB  - A summary of the recommendations for antithrombotic therapy after myocardial
      infarction appears in Table 1. The American College of Cardiology/American Heart
      Association Task Force used a three-tiered classification of therapeutic
      interventions after myocardial infarction. Class I includes interventions that
      are usually indicated, always acceptable, and considered useful and effective.
      Class II includes treatments that are considered acceptable but are of uncertain
      efficacy and possibly controversial. This class is further subdivided into class
      IIa (weight of evidence in favor of usefulness and efficacy) and IIb (not well
      established by evidence, can be helpful, and probably not harmful). Class III
      includes interventions that are not indicated and possibly harmful. None of the
      antithrombotic therapies under consideration in this review were in Class III;
      therefore, this category does not appear in Table 1. Contraindications to
      anticoagulation must, however, be considered before anticoagulant therapy is
      started. To prevent arterial embolism, immediate anticoagulation with heparin
      sufficient to prolong the activated partial thromboplastin time to 1.5 to 2.0
      times control should be initiated in patients with large anterior myocardial
      infarctions. This should be followed by warfarin therapy for at least 3 months in
      patients with anterior or apical wall-motion abnormalities or demonstrated mural
      thrombus. Indefinite oral warfarin therapy may be considered in patients with
      diffusely dilated and poorly contracting left ventricles. For the prevention of
      reocclusion after thrombolytic therapy, aspirin and heparin should be initiated
      immediately. Aspirin should be continued indefinitely; the heparin may be
      discontinued after 24 to 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137062
TI  - Indications for coronary angioplasty.

PMID- 8137063
TI  - Cerebellar infarction.

PMID- 8137064
TI  - Treatment of small deep infarcts of the brain.

PMID- 8137065
TI  - Prevention of heart failure.

PMID- 8137066
TI  - Inspection of the neck veins.

PMID- 8137067
TI  - Modifications of the rate matrix required for the quantitative analysis of NOESY
      spectra of proteins.
AB  - The introduction of rate matrix analysis to protocols for the refinement of
      solution structures of biopolymers on the basis of NMR-derived structural
      constraints has greatly enhanced the self-consistency of the general approach.
      However, current implementations of this strategy appear not to consider several
      issues arising from various commonly employed experimental conditions and sample
      characteristics which can prevent the quantitative interpretation of NOESY
      spectra of proteins. Here, a number of these effects are considered, including
      the influence of nonequilibrium populations generated by over-pulsing and solvent
      presaturation, the presence of heteronuclei, and the equilibration of
      exchangeable sites with deuterium in solvent. The modifications of the rate
      matrix that are required to treat these effects are summarized and simulations
      presented to illustrate the relative importance of each. The computational effort
      required to rigorously accommodate each effect is described along with several
      simple experimental modifications that reduce the computational burden.

PMID- 8137068
TI  - Analysis of double-quantum-filtered NMR spectra of 23Na in biological tissues.
AB  - Double-quantum-filtered NMR spectra of 23Na in bovine nasal cartilage tissue and
      its constituents were measured. The presence of even-rank tensors was detected in
      the cartilage tissue and in a suspension of collagen fibers, indicating
      anisotropic motion of the sodium ions. Quantitative analysis of the spectra was
      performed by calculating the time evolution of the second- and third-rank tensors
      by solving a modified Redfield equation. Analytical expressions for the spectra
      were obtained. It is shown that the anisotropy stems from local rather than
      macroscopic order. A good fit to the observed spectra was obtained for several
      models that assume isotropic distribution of the directors of the locally ordered
      sites. The local residual quadrupolar interaction was found to be 550 Hz,
      demonstrating the sensitivity of double-quantum filtration in the detection of
      anisotropic motion.

PMID- 8137069
TI  - A new strategy for spectroscopic imaging.
AB  - This paper describes a new approach for reducing ringing artifacts in
      spectroscopic imaging (or chemical-shift imaging). The new method is aimed at
      reducing the signal contamination in areas of interest, due to ringing, that
      often arises from adjacent areas with high intensity, such as subcutaneous fat in
      the case of 1H spectroscopy and skeletal muscle in case of the 31P spectroscopy.
      The method is based on the fact that the high-intensity signals which are the
      major source of contamination can be captured with one or few acquisitions and
      the metabolite resonances in areas of interest require considerably more
      averaging in the data acquisition due to low signal-to-noise ratio. In order to
      reduce ringing and maintain adequate SNR for the metabolites, the data points in
      high k space are measured with one or few excitations while those in the low k
      space are sampled with many excitations. By virtue of this sampling scheme, the
      data contain more noise in the high-spatial-frequency region and direct Fourier
      transformation reconstruction generates a very noisy image. Therefore, a new
      reconstruction technique is developed for the reconstruction. This approach has
      been studied by simulations and its practical utility is demonstrated by an in
      vivo proton CSI experiment. Technical details and simulation and experimental
      results are presented. From these results, it is concluded that the technique is
      robust and can be used for in vivo applications.

PMID- 8137070
TI  - Magnetic susceptibility in the vertebral column.
AB  - A magnetic resonance method is described which provides good-quality field
      mapping images of the spine, although the in vivo signals from red bone marrow of
      the vertebral bodies exhibit similar fractions of lipid and water protons with
      their chemical-shift difference of 3.4 ppm. The susceptibilities of bone marrow
      and intervertebral disks were examined in 20 cadaveric human spines, 9 healthy
      volunteers, and 9 patients with degenerative disk alterations. The influence of
      geometrical properties was studied in cylindrical spine phantoms of different
      size and contents with different susceptibility. The measurements reveal
      interindividual differences of the susceptibility of the intervertebral disks in
      healthy subjects. Three out of nine degenerated disks with low signal in T2
      weighted spin-echo images showed irregularities of the field distribution within
      the nucleus pulposus.

PMID- 8137071
TI  - Use of fuzzy mathematics for complete automated assignment of peptide 1H 2D NMR
      spectra.

PMID- 8137072
TI  - Optimized phase scrambling for RF phase encoding.

PMID- 8137073
TI  - The pH dependence of chemical shift and spin-spin coupling for citrate.

PMID- 8137074
TI  - URPI: a utility program for planning selective protein double-labeling with 13C
      and 15N in NMR analyses.

PMID- 8137075
TI  - The influence of the slice-selection gradient on functional MRI of human brain
      activation.

PMID- 8137076
TI  - Two configurations of the four-ring birdcage coil for 1H imaging and 1H-decoupled
      31P spectroscopy of the human head.
AB  - The four-ring birdcage resonator, a new class of dual-tuned birdcage resonators,
      is described. We report two configurations of the coil: the low-pass, high-pass
      (LP-HP) and the low-pass, low-pass (LP-LP), both of which can be operated in dual
      quadrature mode at 1.5 T. As head coils, both configurations exhibit greatly
      reduced tuning interactions between frequencies, permitting rapid, noniterative
      tuning. Compared with single-tuned, two-ring birdcage resonators of similar
      volume, the sensitivity and transmitter efficiencies of the resonators are better
      than 85% for the proton frequency and the same to within 5% for the phosphorus
      frequency. Circuit models have been developed to refine coil tuning and aid the
      calculation of B1 field contour plots. Both configurations have been used for
      integrated examinations involving acquisition of high-quality 1H images and 1H
      decoupled 31P CSI spectra of the human head. A scaled-down version of the LP-LP
      configuration has been demonstrated for use with the human calf.

PMID- 8137077
TI  - Lactate mapping with full sensitivity by spin-filtered NMR imaging.
AB  - The mechanism of the fourfold signal loss during the cyclic polarization-transfer
      (CYCLPOT) sequence for lactate filtering is analyzed using the spin-product
      operator formalism. Based on the results of the analysis, a new sequence,
      RECYCLPOT (refocused CYCLPOT), is proposed and experimentally tested for lactate
      filtering with full sensitivity and specificity. Lactate mapping is performed by
      spin filtering using the RECYCLPOT sequence prior to imaging by spatial encoding.

PMID- 8137078
TI  - Accounting for ligand-protein interactions in the relaxation-matrix analysis of
      transferred nuclear Overhauser effects.

PMID- 8137079
TI  - Assignments and structural information on nucleic acids via PHH correlations.

PMID- 8137080
TI  - Physical and instrumental considerations in the use of lithium phthalocyanine for
      measurements of the concentration of the oxygen.
AB  - The use of crystals of lithium phthalocyanine (LiPc) to measure the concentration
      of oxygen in vivo and in vitro by electron paramagnetic resonance leads to
      experimental constraints due to the very narrow EPR lines that may occur (as
      narrow as 11-13 mG in the absence of O2), distortions induced by the automatic
      frequency control system, anisotropy in the spectra (orientation-dependent
      linewidth is 11-17 mG in the absence of O2), microwave power saturation, and the
      effect of physiological motion. These constraints can be overcome if recognized.
      This article highlights the experimental and theoretical basis of these
      properties of the EPR signal of LiPc and suggests some technical solutions. It is
      most important to recognize that paramagnetic species such as LiPc present
      problems that are not commonly encountered in EPR spectroscopy.

PMID- 8137081
TI  - The relevance to humans of animal models for inhalation studies of cancer in the
      nose and upper airways.

PMID- 8137082
TI  - The relevance to humans of animal models for inhalation studies of cancer in the
      nose and upper airways.
AB  - While nasal cancer is relatively rare among the general population, workers in
      the nickel refining, leather manufacturing, and furniture building industries
      exhibit increased incidences of nasal cancer. To investigate the causes of nasal
      cancer and to design ameliorative strategies, an appropriate animal model for the
      human upper respiratory regions is required. The present report describes,
      compares, and assesses the anatomy and physiology of the nasal passages and upper
      airways of humans, rats, and monkeys for the purpose of determining a relevant
      animal model in which to investigate potential causes of nasal cancer. Based on
      the mode of breathing, overall geometry of the nasal passages, relative nasal
      surface areas, proportions of nasal surfaces lined by various epithelia,
      mucociliary clearance patterns, and inspiratory airflow routes, the rat, which is
      very different from humans, is a poor model. In contrast, the monkey exhibits
      many similarities to humans. Although the monkey does differ from humans in that
      it exhibits a more rapid respiratory rate, smaller minute and tidal volumes,
      larger medial turbinate, and a vestibular wing that creates an anterior vortex
      during inspiration, it offers a more appropriate model for studying the toxic
      effects of inhaled substances on the nasal passages and extrapolating the
      findings to humans.

PMID- 8137083
TI  - Identification of chemicals for testing in the rodent cancer bioassay.
AB  - A recently developed method was used to identify the structural moieties that are
      not represented among the chemicals tested in the U.S. National Toxicology
      Program rodent cancer bioassay. Inclusion of those chemicals in the bioassay
      would increase the informational content of rodent cancer assay data base.

PMID- 8137084
TI  - Quality requirements for biocides in the 1990s.
AB  - Increasing regulatory and product safety standards along with the enhanced
      expectations of today's consumer public have dramatically changed the manner in
      which new biocides are researched, developed, and marketed. Potential candidates
      face ever rising quality hurdles regarding Product Efficacy, Toxicology, Human
      Health and Environmental Risk Assessment and Risk Management, and, ultimately,
      Product Stewardship. These pressures have resulted in long lead times for new
      products with few companies entering into the biocide market. Another resultant
      trend has been a strong tendency to expand the life cycles of existing products.
      This report outlines and summarizes recent activity associated with these quality
      issues and their relationship to the successful marketing of biocides in the
      future.

PMID- 8137085
TI  - Predictions based upon the CASE structure-activity relational method are
      independent of the nature of the chemicals in the data base.
AB  - It is demonstrated that the predictivity of the CASE structure-activity
      relational method is determined by the number of chemicals in the learning set
      but not by the nature of the chemicals. Thus learning sets containing equal
      numbers of different chemicals will be equally predictive of the activity of
      chemicals not in the learning sets. These findings have implications with respect
      to the strategy of selecting chemicals for listing and inclusion in data bases as
      well as for mechanistic studies in which different toxicological endpoints are
      compared.

PMID- 8137086
TI  - Development of a method to assess the informational content of structure-activity
      data bases.
AB  - The ability to predict the biological or toxicological properties of yet untested
      chemicals based upon structure-activity relationships (SAR) is very dependent
      upon the size and chemical diversity of the "learning set" used to develop the
      SAR model. In the present study it is shown that for noncongeneric chemicals,
      systematically increasing the informational contents of "learning sets" by
      iteratively selecting chemicals based upon structural diversity increases the
      predictivity of the SAR model. This approach can now be used to generate learning
      sets with maximal informational content while keeping the number of chemicals
      that require testing at a minimum.

PMID- 8137087
TI  - Planarians as a model system for in vivo teratogenesis studies.
AB  - Planarians are free-living flatworms whose organ systems are capable of carrying
      out complex metabolic functions similar to those of mammals. The biological
      similarity of planarians to mammals, and the ease and low cost of culturing
      planarians in the laboratory, makes them a good in vivo animal for screening and
      mechanistic studies of acute, chronic, neurobehavioral, reproductive, and
      developmental toxicology. Because only undifferentiated totipotent stem cells,
      i.e., neoblasts, are capable of mitosis and differentiation in planarians, all
      abnormal growths, including tumors, originate from this target cell. This review
      evaluates planarians for use in developmental toxicology as a screening bioassay
      for compounds and mixtures, and for mechanistic studies.

PMID- 8137088
TI  - Effectiveness in psychiatric care. III: Psychoeducation and outcome for patients
      with major affective disorder and their families.
AB  - This hypothesis-generating study had the objective of dissecting the process of
      psychiatric care in an attempt to understand outcomes for patients and their
      families. In all, 24 patients who carried a DSM-III diagnosis of major affective
      disorder were identified 12-18 months after hospital admission. The patients,
      their families, and their doctors were interviewed using instruments measuring
      delivery of treatment and achievement of treatment goals; findings were then
      correlated with resolution of the index episode and patient global outcome.
      Delivery of patient and family psychoeducation was associated with better
      resolution of the index episode and better global outcome.

PMID- 8137089
TI  - Is there a delay in the onset of the antidepressant effect of electroconvulsive
      therapy?
AB  - The severity of depression in 11 drug-free unipolar patients diagnosed with
      definite major depressive disorder was assessed using the Hamilton Rating Scale
      for Depression during a course (5-10 treatments) of bilateral electroconvulsive
      therapy (ECT). The degree of improvement after three treatments of ECT was six
      times greater than the improvement that occurred over the remainder of the
      course. Although depressed patients who recover with ECT require repeated
      treatments, the treatments early in a course of ECT can have marked
      antidepressant effect.

PMID- 8137090
TI  - Antidepressant effect of lithium in patients with systemic lupus erythematosus
      and cerebral infarction, treated with corticosteroid.
AB  - Two depressive patients with systemic lupus erythematosus (SLE) and cerebral
      infarction, while being treated with corticosteroid, are described. In both
      cases, lithium was remarkably effective and no severe side-effects occurred.
      These findings suggest that lithium can be a useful antidepressant agent in the
      treatment of depressive SLE patients.

PMID- 8137091
TI  - Malignant alienation. Dangers for patients who are hard to like.

PMID- 8137092
TI  - Debt and deliberate self-poisoning.
AB  - This study is a descriptive survey of financial difficulties in a consecutive
      series of patients who deliberately poisoned themselves. Over three months 160
      such patients presented to the liaison psychiatry service at Leeds General
      Infirmary. Information was available on 147 of these patients, of whom 54 (37%)
      had problem debts. Patients in debt were more likely to harm themselves with
      greater suicidal intent and, after the episode, to report more symptoms of
      depression and hopelessness. Psychiatrists were more likely to diagnose mental
      illness in those in debt.

PMID- 8137093
TI  - Neuroleptic malignant syndrome--a cautionary tale and a surprising outcome.
AB  - Vigilance is required in order to detect the cardinal signs of neuroleptic
      malignant syndrome (NMS), especially after prolonged exposure to neuroleptics. In
      this case, NMS was diagnosed in a 29-year-old man, who had been on fluphenazine
      decanoate for over one year, coinciding with a cessation of his neuroleptic
      medication. Vigorous treatment, including assisted ventilation, was necessary,
      extending over three months. On recovery, his mental state and social functioning
      had undergone a sustained improvement sufficient for his release from hospital.

PMID- 8137094
TI  - Antidepressant effects of ECT.

PMID- 8137095
TI  - Parental bonding.

PMID- 8137096
TI  - Neural network model of amnesia.

PMID- 8137097
TI  - Suicide prevention.

PMID- 8137098
TI  - Late-onset schizophrenia versus late paraphrenia.

PMID- 8137099
TI  - Attachment theory.

PMID- 8137100
TI  - Variations on the theme of euthanasia.

PMID- 8137101
TI  - Variations on the theme of euthanasia.

PMID- 8137102
TI  - DIDMOAD (Wolfram) syndrome.

PMID- 8137103
TI  - Cognitive impairment and clozapine.

PMID- 8137104
TI  - Lithium dosage and inositol levels.

PMID- 8137105
TI  - D2 dopamine receptor binding in the basal ganglia of antipsychotic-free
      schizophrenic patients. An 123I-IBZM single photon emission computerised
      tomography study.
AB  - We used SPECT to examine striatal D2 receptor binding in 20 antipsychotic-free
      DSM-III-R schizophrenic patients and 20 age- and sex-matched normal controls.
      Dynamic single-slice SPECT, at a slice chosen to include the basal ganglia, began
      immediately following intravenous injection of 185 MBq of 123I-IBZM. A
      semiquantitative approach was used to generate indices of specific D2 receptor
      binding in the basal ganglia. There was no overall elevation of D2 receptor
      binding between patients and controls. A male sex-specific left lateralised
      asymmetry of striatal D2 receptor binding was found in the patient group. Age
      dependent decline of striatal D2 receptors was confirmed in controls, but not in
      patients. These results suggest that alterations in striatal D2 receptor
      distribution and density do occur in schizophrenia, and possibly reflect wider
      disruptions in prefrontal-striatal-limbic circuits.

PMID- 8137106
TI  - Functional magnetic resonance imaging. A new technique with implications for
      psychology and psychiatry.

PMID- 8137107
TI  - Central D2 receptors and negative symptoms of schizophrenia.
AB  - Most in vivo studies of striatal D2 receptor (SD2R) density with positron
      emission tomography in schizophrenia have attempted to relate this variable to
      the diagnosis of the illness. In the present study, a relationship between SD2R
      and clinical dimensions of this psychosis was searched for in a highly selected
      group of young negative schizophrenics (8 drug-naive and 2 drug-free). The SD2R
      density index measured in vivo using 76Br-bromolisuride and PET correlated
      negatively (r = 0.80, P < 0.01) with a psychomotor dimension of schizophrenia
      involving blunted affect and alogia. The mean SD2R index of the patients did not
      differ from that of age-matched control subjects. Therefore, this behavioural
      dimension accounts for the variance of the SD2R, suggesting that the striatal
      dopamine system modulates symptoms such as flattened affect and alogia.

PMID- 8137108
TI  - Jealousy: a community study.
AB  - This study represents the first attempt to study sexual jealousy in a random
      community sample. Jealousy was reported by all subjects. Men, when jealous, were
      particularly concerned about the potential loss of the partner, whereas women
      were more concerned with the effects of infidelity on the quality of the
      relationship. Behaviours such as searching the partner's belongings or inspecting
      their clothes for signs of sexual activity correlated with unusually intense
      jealousy. Men tended to cope with jealousy by using denial and avoidance, whereas
      women were more likely to express their distress and to try to make themselves
      more attractive to their erring partner. Greater jealousy concerns were expressed
      by young men who had either married early or were now living without a partner.
      Heavy drinkers and those reporting more psychiatric symptoms were also more prone
      to jealousy. A clear correlation emerged between lowered self-esteem and
      increased jealousy, which was particularly marked in women, for whom robust self
      esteem was virtually incompatible with high jealousy concerns. The study
      supported the prosaic notion that those who are satisfied with their romantic
      attachments are less prone to jealous suspicions. This study offers a starting
      point for the clinician seeking information about the experience of jealousy in
      the community.

PMID- 8137109
TI  - Psychiatric disorder in women serving a prison sentence.
AB  - The paper describes a case-note and interview study of a cross-sectional sample
      comprising 25% of all women serving a prison sentence in England and Wales. A 5%
      sample of the male sentenced prison population was used for comparison. Diagnoses
      were assigned on clinical grounds and an assessment was made of the treatment
      needs of all 'cases'. The prevalence of psychosis, around 2%, was similar in the
      two groups but women had higher rates of mental handicap (6% v. 2%), personality
      disorder (18% v. 10%), neurosis (18% v. 10%) and substance abuse (26% v. 12%).
      There is a need for closer links between the NHS and prison health services.
      Women's prisons lack a therapeutic community of the Grendon type, which may be of
      benefit to a substantial minority of inmates.

PMID- 8137110
TI  - Psychotic men remanded in custody to Brixton Prison.
AB  - All referrals to medical officers in Brixton Prison over a five-month period in
      1989 were examined. This paper reports the progress through this remand prison of
      those men who were considered to be suffering from a major psychiatric disorder.
      Many men had been charged with relatively minor offences. The net effect of
      medical intervention was to delay release from custody. Because of the
      administrative delays inherent in the system of medical referral and hospital
      admission under section 37 of the Mental Health Act 1983, it was those prisoners
      who were most ill who tended to remain in prison for the longest periods. Judged
      in terms of its efficiency to ensure speedy treatment for mentally ill remanded
      offenders, the present system is regarded as cumbersome and extremely
      inefficient. It is suggested that greater use should be made of section 48 of the
      1993 Act to divert mentally ill, remanded offenders from prison.

PMID- 8137111
TI  - Assaultiveness among institutionalised adults with mental retardation.
AB  - In an institution, 57 people with mental retardation who had shown assaultive
      behaviour during the last year were compared with a control group of 57 people in
      the same institution, matched by sex, level of retardation and age. The study
      group were younger and had more people with a moderate level of mental
      retardation than the total population of the institution. Compared with the
      controls, the assaultive group had more resources available, had more
      psychopathology, consumed more psychotropic drugs, and had a higher frequency of
      other problem behaviour. We found no group differences in personal skills,
      including communication. Generally, the observed covariates of assaultive
      behaviour resembled that seen in other populations with assaultive behaviour.

PMID- 8137112
TI  - The Chartres Study: I. Prevalence of psychiatric disorders among French school
      age children.
AB  - A survey of child psychiatric disorders was conducted in a community sample of
      2441 French school-aged children selected from 18 public and private schools;
      children attending special classes were oversampled. A two-stage survey design
      was used to identify disorders. Measures were the Child Behavior Checklist and
      the Rutter teacher scale for screening. The Isle of Wight parental interview was
      used in the second phase for 217 home interviews, along with the Children Global
      Assessment Scale as an index of impaired functioning. Response rates were
      excellent, and non-respondents in the screening phase were shown to have higher
      levels of psychopathology as gauged by their teacher scale scores. Several
      weights were used in the analysis to adjust for differential probabilities of
      selection and participation in each survey phase. The overall prevalence rate
      among 8-11-year-olds was estimated to be 12.4% (5.9% for more severe disorders),
      with roughly equal rates of disruptive and emotional disorders (6.5% and 5.9%).
      Prevalence was higher in boys (15.0%) than in girls (9.5%), owing to a threefold
      increase in their frequency of conduct disturbances. Rates of disturbance were
      twice as high among children with special educational needs, while no difference
      was found between private and public schools. The frequency of behavioural
      problems appeared to be similar in the urban and semi-rural subsamples.

PMID- 8137113
TI  - Chronic physical illness and emotional disorder in childhood. Where the brain's
      not involved, there may still be problems.

PMID- 8137114
TI  - Ten-year follow-up of 50 patients with bulimia nervosa.
AB  - Long-term outcome studies for people suffering from bulimia nervosa are few. Ten
      years after presentation, we followed up 50 patients (49 women, 1 man) who were
      originally involved in a double-blind, controlled trial of the antidepressant
      mianserin. Standardised interviews and questionnaires were used to assess eating
      attitudes and behaviour, psychiatric status and social functioning. A DSM-III-R
      diagnosis was given where appropriate. Sufficient information to make a diagnosis
      was obtained for 44 subjects (88%). Of patients traced, 52% had recovered fully
      and only 9% continued to suffer the full syndrome; 39% continued to experience
      some symptoms. Significant predictors of favourable outcome were younger age at
      onset, higher social class and a family history of alcohol abuse. Outcome for
      bulimia nervosa continues to improve over ten years with the majority of patients
      eventually making a full recovery or suffering only moderate abnormalities in
      eating attitudes. Although predictors of recovery were few, it would appear that
      intervention has a significant impact on ultimate outcome.

PMID- 8137115
TI  - Social adjustment in panic-agoraphobic patients reconsidered.
AB  - Forty-eight depressed panic-agoraphobic patients--clinically matched for severity
      of depression with 35 primary chronic depressives--had significantly better
      adjustment in most areas of social functioning, especially those related to
      interpersonal contact, work, leisure activities, and sexual life. Even when
      depressed, panic-agoraphobic patients appear to possess sufficient interpersonal
      skills--that is, by learning on significant others--to engage in a range of
      social activities, both at home and beyond. These data, which are open to
      different interpretations, nonetheless suggest that anxiety and mood disorders
      differently affect certain key areas of social adjustment.

PMID- 8137116
TI  - Immune exhaustion: driving virus-specific CD8+ T cells to death.

PMID- 8137117
TI  - Enterobacterial hemolysins: activation, secretion and pore formation.
AB  - Two types of enterobacterial hemolysins have been studied in detail: the
      Escherichia coli alpha-hemolysin and the Serratia marcescens hemolysin. Although
      they have similar properties, they differ entirely in the number and structure of
      the proteins that determine their hemolytic activities, in the mechanism and the
      subcellular location of activation and in their secretion mechanisms.

PMID- 8137118
TI  - Phagocytosis of Pseudomonas aeruginosa by macrophages: receptor-ligand
      interactions.
AB  - Phagocytic cells play a critically important role in host defense against
      infection with Pseudomonas aeruginosa. Recent observations on the receptors and
      ligands that mediate ingestion of this bacterium by phagocytic cells and the
      factors that modulate phagocytosis have provided the theoretical underpinning for
      novel therapeutic strategies.

PMID- 8137119
TI  - Hepatitis B virus replication.
AB  - Hepatitis B virus (HBV) is the causative agent of B-type hepatitis in humans and
      the prototypic member of the hepadnaviruses. It is a small enveloped DNA virus
      that replicates via reverse transcription. Although hepadnaviruses are similar to
      retroviruses in basic life cycle and genome organization, recent studies have
      revealed several unique hepadnaviral strategies that optimize exploitation of
      their extremely small circular DNA genomes.

PMID- 8137120
TI  - Structural proteins of hepatitis C virus.
AB  - Despite the lack of an in vitro replication system, genes coding for viral
      proteins of hepatitis C virus have been identified. The putative nucleocapsid
      (p22) and envelope (gp35 and gp58) proteins have been expressed in cells by
      different vectors under various foreign promoters. Detection of antibodies to
      these proteins in patient sera suggests that they are indeed synthesized during
      the course of viral replication.

PMID- 8137121
TI  - On the mechanism of action of quinolone drugs.
AB  - Antibacterial quinolones are thought to inhibit DNA gyrase by trapping the enzyme
      as a complex with the DNA substrate. The precise molecular details of drug-DNA
      and drug-enzyme interactions remain controversial. Here, a model is proposed that
      accounts for the influence of magnesium ions on quinolone-DNA binding.

PMID- 8137122
TI  - Linear DNA of Borrelia species and antigenic variation.
AB  - Members of the genus Borrelia may be unique among prokaryotic organisms in having
      a polyploid genome that is mostly linear. The smaller linear duplex replicons in
      these organisms have been called plasmids, but there is justification for
      designating them minichromosomes instead. The antigenic identities of the agents
      of Lyme disease and relapsing fever are largely determined by these
      extrachromosomal genes.

PMID- 8137124
TI  - British Society for Rheumatology XIth Annual general meeting. Sussex 20-22 April
      1994. Abstracts.

PMID- 8137123
TI  - Plant antioxidant gene responses to fungal pathogens.
AB  - Antioxidant defense systems are a prominent element in plant responses to
      environmental stress. Activated oxygen species have themselves been implicated as
      both a part of the plant's defense against pathogen attack as well as the
      phytotoxic component of photosensitizing fungal toxins. Molecular analyses are
      just beginning to define how plant oxidant and antioxidant genes might integrate
      with other defense responses to provide effective protection against pathogen
      attack.

PMID- 8137125
TI  - Scientific evidence and expert opinion in ACP Journal Club: commentary on
      commentaries.

PMID- 8137126
TI  - Overview of the transmissible spongiform encephalopathies: prion protein
      disorders.
AB  - The subacute transmissible spongiform encephalopathies (TSE) are a complex group
      of neurodegenerative disorders which includes genetic, infectious and sporadic
      forms exemplified by scrapie in animals and Creutzfeldt-Jakob disease in humans.
      An extensive mass of data indicate that the infectious agents which transmit
      these diseases as well as the pathogenic mechanisms leading to clinical signs are
      related to abnormalities of a single cellular protein, designated the prion
      protein (PrP). The goals of this overview are to summarize the characteristics of
      TSEs and of their infectious agents and to indicate how the prion hypothesis is
      consistent with and provides an explanation for them. Transgenic mouse studies
      are emphasized which verify that genetic forms of TSEs are linked to mutations in
      the host PrP gene and that the host species barrier to scrapie infection, scrapie
      incubation time and the distribution of neuropathology, which define scrapie
      prion isolates ('strains'), are determined by the structure of PrP.

PMID- 8137127
TI  - Neuropathology of spongiform encephalopathies in humans.
AB  - The historical aspects and classification of human spongiform encephalopathies
      are reviewed and the newer concept of 'prion dementias' is explored. Guidelines
      for safe laboratory and autopsy handling of spongiform encephalopathy tissues are
      outlined: this includes an update on strategies which are currently thought to be
      effective in decontamination. A wide ranging review of the pathology of the
      various human spongiform encephalopathies includes newly emerging data on
      microglia, and cell-specific and neurodegenerative proteins. A large section of
      this chapter is devoted to the methodology of immunocytochemical demonstration of
      PrP in tissue sections, and the dilemmas inherent in interpretation.
      Clinicopathological correlations are provided for classical cases of spongiform
      encephalopathy, together with the newly recognised atypical dementias associated
      with PrP gene mutations. The pathology of iatrogenic cases of CJD is described.
      The chapter concludes with problems in differential diagnosis, and discussion of
      the histopathological features which help to resolve diagnostic dilemmas.

PMID- 8137128
TI  - Scrapie pathogenesis.
AB  - There is no specific marker for scrapie infectivity, and therefore no means other
      than prolonged bioassay for estimating levels of infection in tissues. Our
      knowledge of replication dynamics depends on precise rodent models which have
      enabled us to determine how the disease spreads and in which cells it replicates.
      We know, firstly, that infection replicates in the lymphoreticular system, and
      can identify a candidate cell; secondly, the factors which control the length of
      the disease process, and how difficult it is to influence this; thirdly, that
      clinical disease depends on access to the nervous system, and that once
      neuroinvasion has occurred, the spread of infectivity in both PNS and CNS is
      along neuroanatomical pathways at a similar rate to slow axonal transport in
      uninfected mice. Infecting the visual pathways of the CNS through the retina has
      shown that spongiform pathology occurs as a consequence of replication, and that
      the Sinc gene, which has a major effect on incubation period length in mice, acts
      by controlling the initiation, but not the rate, of replication. The localisation
      of PrP, a host protein of unknown function which accumulates in an abnormal form
      in diseased animals provides an important pointer to pathogenetic mechanisms.

PMID- 8137129
TI  - Diversity in the neuropathology of scrapie-like diseases in animals.
AB  - The main diagnostic histology in the spongiform encephalopathies consists of a
      degenerative and usually symmetrical vacuolation of neurons and a spongiform
      lesion in the neuropil. Sometimes there can be asymmetry. This pathology is
      usually confined to grey matter, but an additional white matter vacuolation is
      sometimes typical. The degeneration can progress to neuronal necrosis, with
      reactive glial changes. Photoreceptor loss in the retina occurs in some
      experimental models. Cerebral amyloidosis is conspicuous in many types of scrapie
      like pathology in animals, but is sometimes not recognised or may be absent.
      Abnormal immunolabelling with anti-PrP is always associated with both the
      degenerative and amyloid lesion and precedes the occurrence of the degeneration
      in experimental scrapie models. All aspects of the pathology are closely
      controlled by host genetic factors and by the strain of the infecting, causal
      agent.

PMID- 8137130
TI  - Inactivation of SE agents.
AB  - The transmissible agents of the spongiform encephalopathies are relatively
      resistant to inactivation, and accidental transmission has occurred in animals
      and man. Rigorous chemical or physical procedures are required to achieve
      decontamination, and their effectiveness can only be determined by bioassay in
      animals. The best-defined model is scrapie in mice or hamsters, and this has been
      used in many of the studies to establish practical inactivation procedures.
      Although a number of techniques had been considered to be effective, more recent
      observations suggest that some of these may not always be completely reliable.
      Research continues on scrapie inactivation, and work is in progress to extend
      this knowledge to the BSE agent.

PMID- 8137131
TI  - Scrapie strain variation and mutation.
AB  - There are many strains of scrapie, distinguishable by their disease
      characteristics in genetically-defined mice. Numerous distinct strains have been
      isolated in the same mouse strain, indicating that scrapie agents have an
      informational molecule, independent of the host. Strain characteristics are
      stable on serial mouse passage under constant passaging conditions. However,
      changes in the species or mouse genotype used for passage may lead to changes in
      properties which are consistent with the selection of variants which replicate
      faster in the new host, rather than active modification of the agent by the host.
      The fact that this has been observed with biologically cloned strains is evidence
      for mutation in the scrapie agent. Transmissions to mice from natural scrapie and
      BSE suggest that strain variation exists in the field. These findings have
      important implications when considering the molecular nature of the scrapie agent
      and the details of agent-host interactions.

PMID- 8137132
TI  - PrP gene and its association with spongiform encephalopathies.
AB  - The PrP or prion protein plays a key role in the pathogenesis of the
      transmissible spongiform encephalopathies. This 33-35 kD sialoglycoprotein is the
      product of a single host gene which is composed of 2 or 3 exons, a single open
      reading frame and a cytidine/guanidine rich promoter. The structure of the gene
      and the sequence of the protein are highly conserved in various mammals.
      Primarily, transcription of the PrP gene is found in neurons of the central and
      peripheral nervous system but other tissues do express PrP at least at some
      stages of development. Translation of the PrP mRNA and processing of the initial
      gene product result in a 210 amino acid protein with asparagine-linked
      glycosylation of the complex type which attaches itself to the outer leaflet of
      the plasma membrane lipid bilayer by a C-terminal glycosylinositol phospholipid.
      The function of this protein is unknown. Development of the transmissible
      spongiform encephalopathies, and increasing titre of the causative pathogen, are
      associated with the accumulation in and around cells of pleiomorphic aggregates
      of PrP which are partially resistant to proteolytic hydrolysis. These abnormal
      deposits of PrP, and the normal isoform, are transcribed from the same gene and
      so any disease-linked modification of the protein must be post-transcriptional.
      No disease-specific, covalent modifications of PrP have yet been found and some
      simple, conformational change in its secondary, tertiary (or quaternary)
      structure may underlie its role in these diseases. Polymorphisms in the PrP gene
      of different species have been associated with disease but none of these changes
      in primary structure appear to cause protease resistance per se. Preclinical
      inference of disease susceptibility can already be made using PrP genotype
      analysis in man and some animals but developing a cure for these diseases,
      whether by drug or gene therapy, will require a much greater understanding of the
      molecular and cell biology of this gene and its products. This article presents
      current views and understanding of the PrP gene.

PMID- 8137133
TI  - Scrapie associated PrP accumulation and its prevention: insights from cell
      culture.
AB  - Transmissible spongiform encephalopathies (TSEs), Alzheimer's disease and other
      amyloidoses result in the accumulation of abnormally stable, potentially
      amyloidogenic proteins that appear to play central roles in disease pathogenesis.
      Scrapie-infected tissue culture cells have become well-developed models for
      studying how the TSE-specific protein, protease-resistant PrP, is made from its
      apparently normal precursor. The conversion of PrP to the protease-resistant
      state occurs on the plasma membrane or along an endocytic pathway to the
      lysosomes. The protease-resistant PrP has a much longer half-life than normal PrP
      and its accumulation in lysosomes may feature in TSE pathogenesis. Congo red and
      certain sulfated glycans potently inhibit protease-resistant PrP formation or
      stabilization in cell culture. These and other observations suggest that an
      interaction of PrP with glycosaminoglycans is critical in protease-resistant PrP
      accumulation and raises the possibility that therapeutic strategies for TSEs and
      other amyloidoses could be based on blocking (pre)amyloid-glycosaminoglycan
      interactions.

PMID- 8137134
TI  - Transgenetics and cell biology of prion diseases: investigations of PrPSc
      synthesis and diversity.
AB  - Studies with Tg mice have contributed a wealth of new knowledge about the
      synthesis of prion particles and the pathogenesis of both the genetic and
      infectious forms of the prion diseases. Transgenetic studies argue persuasively
      that the 'species barrier' is due to differences in PrP gene sequences among
      mammals.

PMID- 8137135
TI  - Genetic control of nucleation and polymerization of host precursors to infectious
      amyloids in the transmissible amyloidoses of brain.

PMID- 8137136
TI  - Epidemiology and control of bovine spongiform encephalopathy (BSE).
AB  - BSE is a new disease of cattle. The first clinical case occurred in April 1985
      but the existence of a new disease was first confirmed microscopically in
      November 1986. Epidemiological studies show that cattle suddenly became
      effectively exposed to a scrapie-like agent in ruminant-derived feed in the form
      of meat and bone meal in 1981/2. Most cases have occurred in Holstein Friesian
      dairy cattle and have been exposed as calves. There is no evidence that cattle to
      cattle transmission sufficient to maintain the epidemic occurs. The principle
      animal health control measures are bans on the feeding of ruminant derived
      protein to ruminant animals and on the use of specified bovine offals (SBO) for
      feeding to any species of animal or birds. Human health is protected by
      compulsory slaughter and destruction of suspect animals, and a ban on the use of
      their milk, and by prohibiting the use of SBO in food. The SBO are those tissues
      which, in clinically healthy cattle incubating BSE, might conceivably harbour
      infectivity. The effectiveness of the bans is supported by recent evidence of a
      decline in the cattle epidemic. There is no evidence that BSE is a zoonosis.

PMID- 8137137
TI  - Epidemiology of Creutzfeldt-Jakob disease.
AB  - Extensive information on the epidemiology of Creutzfeldt-Jakob Disease (CJD) has
      accumulated since the original transmission of CJD to primates in 1968. One aim
      of this research was to discover the mechanism of natural transmission of CJD but
      the epidemiological evidence virtually precludes case to case transmission as a
      causative mechanism, except in rare iatrogenic cases, and has provided little
      evidence to suggest an environmental 'source of infection'. An understanding of
      the few positive epidemiological findings such as the high incidence in Slovakia
      has depended on major advances in molecular biology rather than on
      epidemiological evidence. The occurrence of Bovine Spongiform Encephalopathy
      (BSE) has however reinforced the importance of having established the
      epidemiological characteristics of CJD and this information is an important
      background on which to evaluate the findings from basic scientific research.

PMID- 8137138
TI  - Developments in diagnosis for prion diseases.
AB  - The protease resistant isoform of prion protein (PrP) is a diagnostic marker of
      spongiform encephalopathies in humans and animals. Immunoblotting is a sensitive
      method but requires either fresh or frozen, unfixed materials.
      Immunohistochemistry using formalin-fixed, paraffin-embedded materials is now
      also considered to be sensitive and comparable to immunoblotting after various
      treatments, especially using the hydrolytic autoclaving method on tissue sections
      before staining. The advantage of this method is that it can be applied to
      routine pathology materials or long preserved materials. The kuru plaque-type
      deposition of PrP suggests abnormalities of the PrP gene, while synaptic-type
      deposition suggests either sporadic CJD or particular familial CJD. PrP gene
      abnormalities are thus related to PrP deposition and modify clinical symptoms and
      their progression. A PrP gene analysis can be done using either preclinical,
      clinical or post-mortem materials.

PMID- 8137139
TI  - Fatal familial insomnia and the widening spectrum of prion diseases.

PMID- 8137140
TI  - Role of PrP in prion diseases.

PMID- 8137141
TI  - The role of lexical status on the phonetic categorization of speech in aphasia.
AB  - Recent results with normal subjects have shown that the locus of the phonetic
      boundary of a speech continuum may change as a function of the word/nonword
      status of the endpoint stimuli. This so-called lexical effect in phonetic
      categorization has been used as evidence for the role of top-down processing in
      speech perception. This study investigated whether aphasic patients show a
      similar influence of lexical status on phonetic categorization. Two test continua
      were created varying in voice-onset time: in one continuum, the two endpoint
      stimuli were word/nonword, i.e., "duke"--"tuke," and in the other continuum, they
      were nonword/word, i.e., "doot"--"toot." Twelve aphasic patients were tested
      including 6 Broca's aphasics and 6 Wernicke/Conduction aphasics. The subject's
      task was to determine whether the first sound of the stimulus was a "d" or "t."
      Broca's aphasics showed a large lexical effect, with the magnitude of the effect
      being greater than that for normals. These results suggest that the Broca's
      aphasics place a heavier reliance on a heuristic strategy than on the perceptual
      information embedded in the test stimuli in making a phonetic categorization. In
      contrast, Wernicke/Conduction aphasics did not show a lexical effect, suggesting
      that these patients are less likely than either normals or Broca's aphasics to
      use heuristic strategies in lexical processing. The overall results are
      considered in relation to current views on language-processing deficits in
      aphasia.

PMID- 8137142
TI  - Reading with the right hemisphere: evidence from transcranial magnetic
      stimulation.
AB  - Although many patients with dominant hemisphere damage retain some reading
      ability, the anatomic substrate of the preserved reading remains controversial.
      We tested the hypothesis that the right hemisphere mediates the reading of some
      patients with acquired dyslexia by using Transcranial Magnetic Stimulation (TMS)
      to assess the effect of transient cortical stimulation on reading. A patient with
      (partially recovered) pure alexia was asked to read aloud briefly presented
      words, half of which were shown in association with TMS of the right or left
      hemisphere. Consistent with the right hemisphere reading hypothesis, stimulation
      of the right but not the left hemisphere disrupted oral reading.

PMID- 8137143
TI  - Comprehension and imitation of syntax following early hemisphere damage.
AB  - Twenty-five children with early left (LL = 16) or right (RL = 9) hemisphere
      damage and 25 age-matched controls were tested on their comprehension and
      imitation of complex coordinate, passive, and relative clause structures using a
      matched experimental design. The predominant deficit exhibited by left-injured
      children was one of significantly impaired imitation coupled with relatively
      preserved comprehension. For RL subjects the deficit was less pronounced in
      either comprehension or imitation. Manipulation of surface and configurational
      features of sentence structure revealed task differences in the pattern of
      correct performance; however, error strategies observed across the two
      methodologies were shown to converge in a number of critical ways, as well as to
      replicate those previously obtained with adult aphasics. The results are
      interpreted as consistent with an early and continuous left hemisphere
      specialization for expressive syntax.

PMID- 8137144
TI  - The role of lip configuration in monkey vocalizations: experiments using
      xylocaine as a nerve block.
AB  - Human and nonhuman primates commonly alter the configuration of their lips during
      vocal production and thereby modify vocal tract length and shape. In nonhuman
      primates, however, the effects of lip configuration on call structure are
      unknown. This study was designed to investigate the importance of lip
      configuration in rhesus monkey (Macaca mulatta) vocal production by temporarily
      blocking lip movement with injections of xylocaine. For "coo" vocalizations, an
      affiliative contact call that is normally produced with protruded lips, the
      xylocaine treatment had no statistically significant effect on call duration or
      characteristics of the fundamental frequency (i.e., features associated with
      respiration and laryngeal function). However, the two formant frequencies (i.e.,
      features resulting from the filtering properties of the supralaryngeal cavity) of
      the call were significantly effected. Specifically, formant frequencies
      increased, as would be expected from an individual incapable of compensating for
      a shortened vocal tract. In contrast to coos, xylocaine had no statistically
      significant effect on the acoustic structure of "noisy screams," a call given in
      response to being attacked by a dominant and produced with retracted lips (i.e.,
      a shortened vocal tract). Results suggest that for some vocalizations, lip
      configuration may be essential for achieving the intended acoustic target,
      whereas for other vocalizations, it is less important.

PMID- 8137145
TI  - Two cases of deep dyslexia in unilingual hispanophone aphasics.
AB  - This paper addresses the interaction between a particular cognitive property
      inherent to the human brain, i.e., the capacity to learn how to process written
      information in a manner such that reading words aloud can become a standard
      aspect of overt behavior, and some of the culture-linked characteristics of the
      written codes invented by the species. First, the paper reiterates that the
      Spanish written code is transparent to the point of entailing full graphophonemic
      conversion, i.e., reading behavior is possible without access to one's memory of
      written words (to one's "logographic lexicon"). The Ardila claim (Ardila, 1991;
      Ardila, Rosselli, & Pinzon, 1989) that certain clinical forms of acquired reading
      disorders which have been reported to occur among various cultural subgroups do
      not occur among unilingual readers of Spanish is then summarized. This is
      followed by two brief case reports of acquired aphasia in native speakers and
      fluent readers of Spanish; prototypical "deep dyslexia" was documented to exist
      in both cases (Ruiz & Ansaldo, 1990). The Ardila claim is thereafter assessed by
      reference to the notions of surface, phonological, and deep dyslexia; parameters
      such as educational background are taken into account in this discussion.

PMID- 8137146
TI  - Sentence completion task in right-brain-damaged right-handers: Eisenson's study
      revisited.
AB  - This study investigated Eisenson's claim (Eisenson, 1962, 1973) that right-brain
      damaged right-handers (RBDs) are impaired on a sentence completion task
      especially when they have to look for abstract words. Five sentences to be
      completed with concrete nouns and five sentences asking for abstract nouns were
      presented to 34 right-brain-damaged patients and to 19 normal control subjects.
      RBDs' performance differed from that of normals on both types of sentences when
      expected words were considered as the only acceptable answers, but was judged
      defective only for the sentences to be completed with abstract nouns when both
      expected words and adequate words were accepted. Moreover, of the RBDs, only 50%
      performed less well than 95% of the control subjects under this last condition.
      Factors such as age, education, and lesion site failed to characterize this
      subgroup of RBDs.

PMID- 8137147
TI  - The effects of task variation on the production of grammatical morphology in
      Broca's aphasia: a multiple case study.
AB  - Generally task variation is not taken into account in discussions about
      agrammatism in Broca's aphasia. Both free speech and speech under constrained
      conditions are classified as "agrammatic speech." In this study, we investigated
      the effects of task variation on the character of agrammatic speech. We employed
      three types of task situations, an interview and two picture description tasks,
      to elicit speech from 16 Dutch and 3 German Broca's aphasics. The two picture
      description tasks differed in the extent to which they necessitated the
      production of grammatical morphology. Various task-dependent changes in the
      character of agrammatic speech were observed. Overall, omission rates of
      grammatical morphemes went down and substitution rates tended to go up in picture
      description as compared to free conversation. Results are discussed by
      contrasting two explanatory concepts, task interaction and strategic variation.

PMID- 8137148
TI  - Sentence comprehension in patients with Alzheimer's disease.
AB  - Twenty-three early-stage dementia of the Alzheimer type (DAT) patients and twenty
      three control subjects were tested on a sentence-picture matching test containing
      nine different sentence types representing different levels of syntactic
      complexity. Subjects chose between drawings depicting a target sentence and a
      syntactic foil. Results indicated that DAT patients differed from control
      subjects on four of the nine sentence types. Performance of the patients was not
      poorer for sentences that were syntactically more complex, but was poorer for
      sentences that had two propositions as compared to one. Results are discussed in
      terms of a post-interpretative processing impairment in sentence comprehension in
      DAT.

PMID- 8137149
TI  - Membrane-bound choline-O-acetyltransferase in rat hippocampal tissue is
      associated with synaptic vesicles.
AB  - Some of the choline-O-acetyltransferase (EC 2.3.1.6; ChAT) in rat hippocampal
      nerve terminals is non-ionically associated with membranes. The intent of the
      present report was to ascertain whether any of this membrane-bound ChAT might be
      associated with synaptic vesicles. To test this possibility, synaptosomal (P2)
      fractions were hypo-osmotically shocked in water, salt washed to remove ionically
      bound ChAT, subjected to sucrose density gradient centrifugation, and the
      activity of ChAT compared with the amount of occluded ACh in the various
      subcellular fractions. A peak of ChAT and occluded ACh occurred in that fraction
      of the gradient (0.4 M sucrose) acknowledged to be enriched in synaptic vesicles.
      In other experiments, Immunobeads coated with an antibody directed against the
      synaptic vesicle specific SV2 protein immunoprecipitated both ChAT and occluded
      ACh from the 0.4 M sucrose fraction, but no other fraction. Immunobeads coated
      with an anti-ChAT antiserum immunoprecipitated synaptophysin from the 0.4 M
      sucrose fraction, an effect which was blocked by pretreatment of the anti-ChAT
      Immunobeads with purified ChAT. These results suggest that some of the membrane
      bound ChAT in rat hippocampal nerve terminals is associated with cholinergic
      synaptic vesicles.

PMID- 8137150
TI  - Autoradiographic localization of receptors for neuropeptide FF, FLFQPQRFamide, in
      human spinal sensory system.
AB  - The regional distribution of FLFQPQRFamide binding sites on fresh unfixed
      cryostate sections from post mortem specimens of human spinal cord and lower
      medulla oblongata was studied by quantitative autoradiographic methods using
      [125I]YLFQPQRFamide as ligand. Samples were taken from five cases who had died
      with no history of neurological disease at ages ranging from 5 months to 66
      years. The biochemical and pharmacological characteristics of [125I]YLFQPQRFamide
      binding to mounted tissue sections were comparable to those reported for the rat
      in a previous study. [125I]YLFQPQRFamide appeared to interact reversibly with
      high affinity binding sites (Kd = 0.06 nM), distinct from opiate receptors. Sites
      labelled with [125I]YLFQPQRFamide were distributed unevenly within the human
      spinal cord and lower medulla oblongata, with the highest density in the
      superficial layers of the dorsal horn and the spinal trigeminal nucleus. Although
      moderate labelling was observed in the ventral part of spinal grey matter, dense
      labelling appeared in the gracile and cuneate nuclei. No binding sites were
      detected in white matter. These results show that, as in the rat, FLFQPQRFamide
      receptors in the human spinal cord and lower medulla oblongata, are mainly
      concentrated within spinal areas implicated in the analgesic action of opiates.
      The possible role of these receptors in modulating spinal nociceptive information
      is discussed with respect to the pharmacological effects of substances acting on
      FLFQPQRFamide receptors in animals.

PMID- 8137151
TI  - Alterations in behavioral responses to stressors following excitotoxin lesions of
      dorsomedial hypothalamic regions.
AB  - The dorsomedial hypothalamus is important for regulation of cardiovascular
      responses associated with emotional arousal. This region has also been identified
      as a component of neural circuitry involved in fear/anxiety, yet clear evidence
      as to the effects of lesioning on stress-related behaviors is missing. In this
      study, we lesioned the dorsomedial hypothalamic region with the neurotoxin,
      ibotenic acid (IBO; 2.0 micrograms in 0.2 microliter), and studied the impact on
      spontaneous and unlearned behavioral responses to stressors. In the open field
      test, we observed non-generalized increases in motility parameters in the IBO
      rats with the differences occurring in the latter two-thirds of the test. In the
      elevated plus-maze, the IBO rats displayed a classic anxiolytic response with a
      greater proportion of entries into (and greater time spent in) the open arms of
      the maze. In the environment-specific social interaction (SI) test, the IBO rats
      showed a normal familiar/unfamiliar environment discrimination with respect to
      Total SI; however, the composition of the behaviors ('curiosity' vs. physical
      contact) by the IBO rats was markedly altered, with there being a 2-fold increase
      in non-violent physical interactions. Additionally, the differences in these
      traditional indices of anxiety were associated with lesioned animals exhibiting
      greater acoustic startle responsiveness than controls as a function of prepulse
      intensity. Overall, the results following IBO lesions indicate an altered
      responsiveness to sudden stressors, particularly as relates to novelty or
      exploration-oriented behaviors. The hypothalamic lesion may, therefore, have
      resulted in a disinhibition of normally suppressed responding to innate fear or
      challenging stimuli. This study contributes to those that have begun to define
      neural interactions that are essential for integrated stress responses.

PMID- 8137152
TI  - Ontogeny of light-induced Fos-like immunoreactivity in the hamster
      suprachiasmatic nucleus.
AB  - Light induction of Fos within the Syrian hamster suprachiasmatic nucleus (SCN)
      occurred first at postnatal day 4. The number of cells with light-induced Fos
      like immunoreactivity (Fos-LI) per unit volume of SCN increased with age.
      Blinding experiments were used to demonstrate that the eye, though possessing an
      immature retina, appears to be necessary for light induction of Fos. In neonatal
      hamsters, environmental cycles (e.g., light and darkness) may be able to
      reinforce the effect of maternal melatonin in synchronizing the pup's clock.

PMID- 8137153
TI  - Effect of vagotomy on hyperactivity and increased dopamine turnover induced by
      intraperitoneal administration of thyrotropin-releasing hormone.
AB  - Thyrotropin-releasing hormone (TRH) injected intraperitoneally at doses of 10
      mg/kg and 20 mg/kg induced marked hyperactivity in rats. Although regional levels
      of brain dopamine and its metabolites (DOPAC and HVA) in vagotomized rats did not
      differ from those in sham-operated controls, the (DOPAC + HVA)/dopamine ratio, an
      indicator of dopamine turnover, was significantly higher in the nucleus accumbens
      of TRH-treated sham-operated rats than that in untreated sham-operated controls.
      TRH injection induced hyperactivity only in sham-operated rats and not in
      subdiaphragmatic bilaterally vagotomized rats. Similarly, bilateral vagotomy
      completely abolished the TRH-induced increases in dopaminergic turnover in the
      nucleus accumbens. These results suggest that the dopaminergic system in the
      nucleus accumbens is involved in hyperactivity induced by TRH, and that TRH
      mainly affects peripheral receptors. The vagal nerve may be the major pathway
      from the visceral organs to the brain involved in the etiology of hyperactivity.

PMID- 8137154
TI  - Striatal extracellular dopamine levels are not increased by hyperglycemic
      exacerbation of ischemic brain damage in rats.
AB  - We tested the hypothesis that hyperglycemic exacerbation of incomplete forebrain
      ischemia is mediated by increased extracellular dopamine levels. Normoglycemic
      and hyperglycemic Sprague-Dawley rats (eight each) with previously placed coaxial
      striatal microdialysis probes underwent 12 min of forebrain ischemia produced by
      bilateral carotid artery occlusion and trimethaphan-induced hypotension.
      Microdialysis was performed before, during, and for 6 h after ischemia, then
      perfusion-fixation was performed. Hyperglycemic rats had more severe postischemic
      damage in the caudate-putamen, neocortex, and hippocampus. Extracellular striatal
      dopamine levels were increased by ischemia, but were unaffected by hyperglycemia.
      These data show that hyperglycemic exacerbation of ischemic striatal damage does
      not depend on elevated extracellular dopamine levels.

PMID- 8137155
TI  - Inhibition of opiate tolerance by non-competitive N-methyl-D-aspartate receptor
      antagonists.
AB  - Our laboratory and others have previously reported that the non-competitive N
      methyl-D-aspartate (NMDA) receptor antagonist, MK-801, interferes with the
      development of tolerance to the analgesic effects of morphine. The present
      studies were performed in order to further characterize the role of NMDA
      receptors in opiate tolerance. The results demonstrate that opiate tolerance is
      inhibited rapidly, and at low doses, by four different non-competitive NMDA
      receptor antagonists (MK-801, ketamine, dextrorphan and phencyclidine),
      suggesting that this inhibition results from blockade of NMDA receptors rather
      than from the 'side-effect' of a particular drug. The NMDA antagonists were found
      to inhibit the development but not the expression of opiate tolerance; i.e. they
      were able to prevent but not reverse tolerance. Finally, the results suggest that
      NMDA receptor antagonists do not interfere with associative tolerance; instead it
      appears that these drugs may specifically inhibit non-associative tolerance. It
      thus appears that NMDA receptors may have a fundamental role in the development
      of opiate tolerance, and that non-competitive NMDA receptor antagonists may be
      effective adjuncts to opiates in the treatment of chronic pain.

PMID- 8137156
TI  - Chronic 1,25-dihydroxyvitamin D3-mediated induction of nerve growth factor mRNA
      and protein in L929 fibroblasts and in adult rat brain.
AB  - We have proposed that elevating levels of nerve growth factor (NGF) in the CNS is
      a rational strategy for treating certain neurodegenerative disorders. The present
      studies were conducted to determine: (1) if pharmacologically induced levels of
      NGF could be sustained for an extended time, and (2) if correlations exist
      between increases in NGF mRNA and NGF protein in L929 cells and in vivo. Short
      term treatment of L929 cells with 1,25-dihydroxyvitamin D3 resulted in a two-fold
      increase in both NGF mRNA and NGF protein. These increases were sustained for up
      to 48 h with continuous exposure to 1,25-dihydroxyvitamin D3. In rats, 1,25
      dihydroxyvitamin D3 (2.5 nmol; i.c.v.) induced NGF mRNA transiently, with peak
      two-fold increases observed 4 h post-injection. In contrast to L929 cells, 1,25
      dihydroxyvitamin D3 did not elicit an increase in NGF protein after a single
      administration in vivo. However, consistent with long-term exposure in L929
      cells, chronic 6 day infusion of 1,25-dihydroxyvitamin D3 resulted in induction
      of both NGF mRNA and NGF protein in the brain. These results indicate that 1,25
      dihydroxyvitamin D3-mediated NGF induction in cultured L929 cells may predict of
      NGF induction in vivo, suggesting that L929 cells may have utility in studying
      underlying mechanisms of NGF induction by 1,25-dihydroxyvitamin D3. On the basis
      of NGF's ability to increase cholinergic function in animal models of cholinergic
      degeneration, these results are supportive of a role for NGF inducers as
      potential drugs for neurodegenerative disorders.

PMID- 8137157
TI  - Developmental expression in the rat cerebellum of SC1, a putative brain
      extracellular matrix glycoprotein related to SPARC.
AB  - In the nervous system, extracellular matrix (ECM) molecules have been shown to
      have effects on cell migration, process outgrowth and the survival of neurons.
      Recently we have described the molecular cloning of SC1, a putative brain
      extracellular matrix glycoprotein, showing partial similarity to the ECM
      glycoprotein SPARC/osteonectin. We have now examined the expression of SC1 during
      the development of the rat cerebellum at both the protein and mRNA levels. Our
      results indicate that SC1 is both temporally and spatially regulated during this
      process. Bergmann glial cells express SC1 mRNA and the resultant protein is
      deposited along the length of their radial fibres during the process of granule
      cell migration in the developing cerebellum. SC1 mRNA and protein is also found
      in the adult cerebellum, concentrated in the Bergmann glial cells and their
      radial processes, indicating that this putative ECM molecule continues to play
      roles in the central nervous system after migration and proliferative events have
      ceased.

PMID- 8137158
TI  - Dopamine agonists and stress produce different patterns of Fos-like
      immunoreactivity in the lateral habenula.
AB  - In rats treated systemically with either amphetamine, amfonelic acid or
      apomorphine, large numbers of cells displaying Fos-like immunoreactivity (FLI)
      could be seen in the lateral zone of the lateral habenula. The induction of FLI
      by amphetamine could be blocked either by pretreatment with haloperidol or by 6
      hydroxydopamine lesions of ascending dopamine fibers at the level of the lateral
      hypothalamus. In contrast, a variety of stressors selectively induced FLI in the
      most medial portion of the lateral habenula. These findings support the concept
      of a functional differentiation of the medial and lateral regions of the lateral
      habenula and provide further evidence for involvement of the habenula in the
      circuitry of the basal ganglia.

PMID- 8137159
TI  - Dehydroepiandrosterone sulfate alters synaptic potentials in area CA1 of the
      hippocampal slice.
AB  - The influences of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) on
      neuronal properties and synaptic transmission in area CA1 of the hippocampus were
      examined using a slice preparation. DHEAS had no apparent effects upon cell
      membrane resistance or active cell responses to intracellular hyperpolarizing or
      depolarizing current pulses. However, DHEAS did increase the excitability of CA1
      neurons in response to Schaffer collateral synaptic stimulation. This was
      apparent both in field potential recordings as well as intracellular recordings.
      Effects appeared within minutes following exposure to DHEAS and were reversible,
      suggesting a non-genomic mechanism of action. Intracellular recordings indicated
      that DHEAS increased the amplitudes of EPSPs associated with stimulation of
      Schaffer collateral fibers. The increased EPSP amplitudes resulted from DHEAS
      effecting an inhibition of fast IPSPs as well as a direct enhancement of
      excitatory synaptic transmission. No significant effects on slow IPSPs were
      noted. In summary, neurosteroids such as DHEAS may influence synaptic
      transmission through multiple mechanisms. Such influences result in increased
      excitability of postsynaptic neurons and indicate the profound influences
      neurosteroids may have to regulate neuronal activity in intact CNS structures.

PMID- 8137160
TI  - Anoxia reduces depolarization induced calcium uptake in the rat hippocampal
      slice.
AB  - Veratridine-induced depolarization caused a large increase in Ca uptake in the
      rat hippocampal slice (30.2 vs. 9.0 nM/mg dry weight). This uptake was reduced to
      18.4 nM/mg when veratridine was combined with anoxia. When compared with
      veratridine exposure alone, the combination of anoxia and veratridine increased
      intracellular Na (460 vs. 380 microM/g), decreased intracellular K (30 vs. 40
      microM/g) and decreased ATP levels (0.1 vs. 0.8 nM/mg). The changes in Na, K, and
      ATP should enhance net Ca uptake, yet Ca uptake was reduced. This suggests an
      effect of anoxia to block Ca channels. In summary anoxia attenuates
      depolarization-induced Ca uptake. This may represent a mechanism by which neurons
      are partially protected against anoxic damage which could be more severe if
      depolarization-induced Ca uptake was not limited.

PMID- 8137161
TI  - Brain neuromediator systems in the immune response control: pharmacological
      analysis of pre- and postsynaptic mechanisms.
AB  - The involvement of the dopaminergic (DAergic), GABAergic and serotoninergic (5
      HTergic) synaptic mechanisms in neuroimmunomodulation are considered. It is shown
      that the central DA- and GABAergic systems exert a stimulatory influence on the
      immune reactivity. Activation of postsynaptic DA receptors with apomorphine and
      (+)(3-hydroxyphenyl)-N-n-propylpiperidine [(+)-3-PPP] at high doses, D2 receptor
      activation with quinpirole, as well as DA reuptake blockade with amantadine and
      bupropion, resulted in an increase in the immune response. The intensity of the
      immune response was also increased during activation of the GABAergic system with
      the GABA agonist muscimol or the benzodiazepine agonists diazepam and tazepam. On
      the other hand, decreases in the activity of either system by different drugs
      inhibiting DAergic and GABAergic neurotransmission (antagonists of DA
      postsynaptic receptors haloperidol at 1.0 mg/kg and (-)-3-PPP at 6.8 mg/kg,
      agonists of DA autoreceptors apomorphine at 0.02 mg/kg, (-)- and (+)-3-PPP at 1.7
      and 3.4 mg/kg, antagonist of GABA receptors bicuculline, blocker of chloride
      channels picrotoxin, blockers of benzodiazepine receptors Ro 15-1788 and Ro 15
      3505) produce suppression of the immune response. The 5-HTergic system is
      involved in the inhibitory mechanism of neuroimmunomodulation. 5-HT reuptake
      blockade with 4-(5,6-dimethyl-R-benzophuranil)-piperidine (CGP-6085A) and
      sertraline led to immunosuppression.

PMID- 8137162
TI  - Effects of serotonin on hilar neurons and granule cell inhibition in the guinea
      pig hippocampal slice.
AB  - Intracellular recordings in guinea pig hippocampal slices were used to study the
      effects of serotonin (5-HT) on presumed inhibitory hilar neurons and on
      postsynaptic inhibition of granule cells. 5-HT applied by the bath hyperpolarized
      only 50% of the hilar neurons tested but all CA3 neurons and granule cells,
      presumably by activating a K-conductance. The bath application of 4-aminopyridine
      (4-AP, 50 microM) induced burst discharge activity in hilar neurons and giant
      inhibitory postsynaptic potentials (IPSPs) in granule cells consisting of a Cl-
      and K-component. 5-HT (5-10 microM) reversibly blocked the K-component of giant
      IPSPs in granule cells, but not their Cl-component. In the majority of hilar
      neurons 5-HT increased the frequency of 4-AP induced burst discharges even when
      hilar neurons were hyperpolarized. Only in a few hilar neurons 5-HT blocked 4-AP
      induced burst discharges. We conclude that the changes in burst discharge pattern
      of hilar neurons correspond with the differential effect of 5-HT on Cl- and K
      mediated inhibition of granule cells.

PMID- 8137163
TI  - Neuro-glial neurotrophic interaction in the S-100 beta retarded mutant mouse
      (Polydactyly Nagoya). II. Co-cultures study.
AB  - The homozygote of a mouse strain with genetic polydactyly (Polydactyly Nagoya,
      Pdn) shows several brain abnormalities, and significant decrease of S-100 beta in
      the brain [17]. An accompanying paper [18] demonstrates that the hippocampus and
      caudo-dorsal cortex of homozygote (Pdn/Pdn) mouse were markedly reduced in S-100
      beta positive astrocytes and serotonergic fibers, and the content of 5-HT and 5
      HIAA of hippocampus and cortex of Pdn/Pdn mouse was lower than those of
      heterozygote (Pdn/+) or wild type (+/+) mice. To further clarify the effects of
      target tissues from different type brains on the development of serotonergic
      neurons, raphe neurons from Pdn/Pdn or +/+ newborn mice were co-cultured with
      hippocampus or cortex of +/+ or Pdn/Pdn newborn mice. The growth of the
      serotonergic neurons in the mesencephalic raphe tissue dissociated cultures was
      estimated by measuring the specific uptake of [3H]5-HT. The development of both
      genotypes (Pdn/Pdn and +/+) of serotonergic neurons was enhanced by co-cultures
      with target tissues (hippocampus and cortex) of +/+ brain. This effect was not
      observed in the co-cultures with Pdn/Pdn brain as a source of target tissue. The
      present results support the idea that the developmental defect of serotonergic
      fibers in the Pdn mutant mouse is caused by the deficiency of S-100 beta in the
      astrocyte of this mutant, and suggest that S-100 beta is a serotonergic growth
      factor. This mutant mouse is a useful in vivo model to study neural-glial
      neurotrophic interactions.

PMID- 8137164
TI  - Adenylyl cyclase activity and G-protein subunit levels in postmortem frontal
      cortex of suicide victims.
AB  - Basal and stimulated adenylyl cyclase activities and Gs and Gi protein alpha
      subunit levels (Gs alpha and Gi alpha) were compared in postmortem frontal cortex
      from 18 suicide cases and 22 matched controls. Basal, guanosine 5'-O-(3
      thiotriphosphate) (GTP gamma S) stimulated and forskolin stimulated enzyme
      activities were significantly lower in the suicide cases, compared to controls.
      These effects were most apparent in those suicides that had died from violent
      means or that had had a history of depression and appeared to reflect the lowered
      basal activity rather than a reduced ability of either GTP gamma S or forskolin
      to activate the enzyme. No significant correlations were found between adenylyl
      cyclase activity and either subject age or postmortem delay. Western blotting
      revealed no significant differences in Gs alpha and Gi alpha levels between
      control and suicide cases. However, levels of the smaller Gs alpha isoform (Gs
      alpha-S) showed a tendency to be increased in the violent death suicide and
      depressed suicide subgroups, compared to controls. Levels of the larger Gs alpha
      isoform (Gs alpha-L) showed a significant positive correlation with subject age.
      Gi alpha levels showed a significant negative correlation with subject age and a
      positive correlation with postmortem delay. These results support the hypothesis
      that suicidal behaviour and depressive illness may be associated with an altered
      regulation of adenylyl cyclase.

PMID- 8137166
TI  - Cholecystokinin and neuropeptide Y receptors on single rabbit vagal afferent
      ganglion neurons: site of prejunctional modulation of visceral sensory neurons.
AB  - A [125I]cholecystokinin (CCK) analog and [125I]peptide YY (PYY) were used to
      localize and characterize CCK and neuropeptide Y (NPY) receptor binding sites in
      the rabbit vagal afferent (nodose) ganglion. High concentrations of CCK and NPY
      binding sites were observed in 10.6% and 9.2% of the nodose ganglion neurons,
      respectively. Pharmacological experiments using CCK or NPY analogs suggest that
      both subtypes of CCK (CCK-A and CCK-B) and NPY (Y1 and Y2) receptor binding sites
      are expressed by discrete populations of neurons in the nodose ganglion. These
      results suggest sites at which CCK or NPY, released in either the nucleus of the
      solitary tract or a peripheral tissue, may modulate the release of
      neurotransmitters from a select population of visceral primary afferent neurons.
      Possible functions mediated by these receptors include modulation of satiety,
      opiate analgesia, and the development of morphine tolerance.

PMID- 8137165
TI  - Disruption of the blood-cerebrospinal fluid barrier by transient cerebral
      ischemia.
AB  - The influence of transient cerebral ischemia on blood-brain and blood
      cerebrospinal fluid (CSF) barrier permeability was studied sequentially by
      magnetic resonance imaging (MRI) contrast enhancement using gadolinium-diethylene
      triamine pentaacetic acid (Gd-DTPA) in rats. The unilateral internal carotid and
      middle cerebral arteries were transiently occluded by inserting a nylon thread
      into the carotid artery and removing it following a variable interval of 5 to 60
      min. Contrast enhancement of the lateral ventricle on the affected side was seen
      in the enhanced T1-weighted image at the early stage of reperfusion 6 h after the
      start of ischemia in most of the rats subjected to 30- and 60-min ischemia, and
      in 3 of 6 rats in the 15-min ischemia group. Autoradiograms of Gd-[14C]DTPA in
      rats subjected to 60-min ischemia demonstrated that the tracer strongly
      accumulated in the choroid plexus, the wall of the lateral ventricle and its
      surrounding brain tissue. On the other hand, parenchymal enhancement of the
      striatum was seen only in the 60-min ischemia group and appeared later on Day 1
      or Day 7. These results indicate that ventricular enhancement on MRI in this
      model is caused by disruption of the blood-CSF barrier at the choroid plexus of
      the lateral ventricle. This is the first reported study to demonstrate blood-CSF
      barrier disruption by transient ischemia.

PMID- 8137167
TI  - Calbindin D-28k as a marker for the associative cortical territory of the
      striatum in macaque.
AB  - An immunohistochemical study was made to investigate the topographic distribution
      of calbindin D-28k in relation to the associative and sensorimotor cortical
      territories in the macaque striatum. An intense calbindin-staining was found in
      the caudate nucleus and ventromedial putamen, i.e., in the associative striatum.
      In contrast, only a weak immunoreaction was found in the dorsolateral,
      sensorimotor, putamen. Calbindin immunoreactivity thus appears as a specific
      marker for the associative striatum.

PMID- 8137168
TI  - Effect of phencyclidine on dopamine release in the rat prefrontal cortex; an in
      vivo microdialysis study.
AB  - The effect of phencyclidine (PCP) on the extracellular dopamine levels in the rat
      prefrontal cortex was investigated using an in vivo brain dialysis technique. PCP
      increased extracellular dopamine levels in the prefrontal cortex of freely-moving
      rats after the systemic (7.5 mg/kg i.p.) or the local injection (100 microM and
      500 microM). The local injection of MK-801, which is a more selective and potent
      NMDA receptor antagonist than PCP also increased the extracellular dopamine
      levels (from 10 microM to 100 microM). These results suggest that part of the
      effect of PCP is attributable to its antagonist effect on the NMDA receptor.

PMID- 8137169
TI  - Excitation of the motor cortex associated with the E2 phase of cutaneous reflexes
      in man.
AB  - We investigated excitability changes of the motor cortex associated with the E2
      phase of cutaneous reflexes in the first dorsal interosseous muscle using
      transcranial electrical and magnetic stimulation of the motor cortex in humans.
      EMG responses to combined cutaneous and weak magnetic cortical stimulation, which
      were elicited during the E2 phase of cutaneous reflexes, were larger than those
      by the same magnetic cortical stimulation alone. This facilitatory effect was
      reduced or even inhibitory effect was seen when the intensity of cortical
      stimulation was increased. Responses to weak electrical cortical stimulation were
      less affected by the combined cutaneous stimulation. The same facilitatory effect
      on responses to weak magnetic cortical stimulation was also observed in single
      motor unit recordings, too. Dissociation between facilitatory effects on the
      responses evoked by weak magnetic and weak electrical cortical stimulations
      suggests that the motor cortical excitability is increased in association with
      the E2 phase. The present results are consistent with the hypothesis that the E2
      phase is a kind of transcortical reflex.

PMID- 8137170
TI  - Elevation of the neurotoxin quinolinic acid occurs following spinal cord trauma.
AB  - Excitatory amino acid neurotoxicity and the inflammatory response are suspected
      as mediators of some of the pathological sequelae occurring as a result of spinal
      cord injury. Here we report temporal and regional increases of the NMDA receptor
      agonist, quinolinic acid (QUIN), in an experimental model of spinal contusion
      injury. These changes occurred at a time when the blood-brain barrier is known to
      be dysfunctional and the activation state and density of microglia and
      macrophages are increased. Thus, alterations in tissue QUIN levels may occur as a
      result of secondary activation of CNS inflammatory cells or from peripherally
      derived sources across a damaged blood-brain barrier.

PMID- 8137171
TI  - Auditory selective attention in the human cochlea.
AB  - According to current theories, auditory selective attention alters the sensory
      analysis of acoustic inputs only in the central auditory system. Despite numerous
      attempts, no evidence of attentional selection has been found in the auditory
      periphery. Measurements of evoked otoacoustic emissions (EOAEs) during a
      selective dichotic listening task showed that the EOAEs to tones in one ear had
      larger amplitude when attention was directed to this ear than when attention was
      directed to the opposite ear. The results indicate that genuine effects of
      auditory selective attention can be observed at the cochlear receptor.

PMID- 8137172
TI  - Early blood-brain barrier changes in the rat following transient complete
      cerebral ischemia induced by cardiac arrest.
AB  - This study examined regional patterns of increased vascular permeability
      following transient global cerebral ischemia. Rats underwent 3.5, 5 or 10 min of
      cardiac vessel bundle occlusion, i.e. cardiac arrest. The animals were killed at
      2, 3, 5 and 15 min, or 1, 3, 6 and 24 h after global cerebral ischemia. Thirty
      minutes before the end of each blood recirculation period, the electron dense
      protein tracer--horseradish peroxidase (HRP) was intravenously injected and rats
      were perfusion-fixed for light and electron microscopic analysis. Control rats
      showed no HRP leakage. Post-ischemic rats demonstrated random blood-brain barrier
      (BBB) alterations. Permeability alterations were spotty and widespread in
      cortical, thalamic, basal ganglia, hippocampal, brain stem regions, cerebellum
      and white matter. Peroxidase extravasation frequently involved arterioles, veins
      and venules surrounded by perivascular spaces. Routes of increased HRP
      permeability included endothelial cell (EC) vesiculo-canalicular profiles and
      diffuse leakage through damaged ECs. Barrier damage determined by HRP
      permeability revealed a biphasic nature. The first stage appeared immediately
      after ischemia at the 2nd min and involved the 1st post-insult hour. There was no
      HRP leakage in rats sacrificed 3 h after insult. BBB opening appeared again 6 h
      after ischemia and remained open 24 h after cardiac arrest. The openings of BBB
      did not increase in frequency with longer periods of ischemia and recirculation.
      These results demonstrate that cardiac arrest produces a spotty BBB disturbances
      at vessel bifurcations and suggest that BBB changes associated with cardiac
      arrest may be multifactorial in time course and location.

PMID- 8137173
TI  - Proteolytic processing of the Aplysia A peptide precursor in AtT-20 cells.
AB  - When the Aplysia ELH precursor is expressed in AtT-20 cells, the carboxyterminal
      derived peptides are packaged and stored in secretory vesicles, while the
      aminoterminal region of the precursor is constitutively secreted. In contrast,
      when the highly homologous A peptide precursor is transfected into AtT-20 cells,
      both aminoterminal and carboxyterminal derived peptides are packaged in storage
      granules. We propose that this is due to the fact that the initial cleavage of
      the A peptide precursor occurs more slowly, and perhaps later in the secretory
      pathway, than the ELH precursor. We further suggest that in the A peptide
      precursor, the first cleavage occurs after the sorting site resulting in co
      packaging of the multiple products derived from a single precursor protein. To
      determine the structural features of the prohormones responsible for this
      differential sorting, we made chimeric precursors and determined the rates of the
      initial cleavage as well as the efficiency of storing the peptide products. From
      these studies, we conclude that the differential sorting is regulated both by the
      amino acid sequence of the first processing site, and by more global aspects of
      the precursor structure.

PMID- 8137174
TI  - Acetyl-L-carnitine treatment increases choline acetyltransferase activity and NGF
      levels in the CNS of adult rats following total fimbria-fornix transection.
AB  - Transection of the fimbria-fornix in adult rats is a useful model for producing
      impairments of cholinergic activity in the hippocampus (HIPP) and atrophy of the
      medial septum cholinergic perikarya, similar to those observed during senescence,
      that are possibly due to the lack of nerve growth factor (NGF) retrogradely
      transported from the hippocampus. In our investigation we used choline
      acetyltransferase (ChAT) as an index of cholinergic activity in HIPP, frontal
      cortex (FCX), septum and nucleus basalis magnocellularis (NBM) along with
      measurements of NGF levels in the HIPP. Three-month-old rats with unilateral
      total fimbria transection received acetyl-L-carnitine (ALCAR) (150 mg/kg/day) in
      drinking water for 1 week before and 4 weeks after the lesion). ALCAR is a
      substance known to ameliorate some morphological and functional disturbances in
      the aging central nervous system (CNS). ChAT activity in septum and FCX, and NGF
      levels in HIPP were significantly increased in the treated group, compared with
      untreated control groups, while no changes were found in the NBM. On the other
      hand, a similar ALCAR treatment in unoperated animals induced an increase in ChAT
      activity in FCX but not in septum nor in NBM. These data are suggestive of a
      neurotrophic property of ALCAR exerted on those central cholinergic pathways
      typically damaged by aging.

PMID- 8137175
TI  - Astrocytes and catalase prevent the toxicity of catecholamines to
      oligodendrocytes.
AB  - Metabolism of catecholamines can generate reactive free radical species,
      including hydrogen peroxide (H2O2), that are potentially harmful to cells. In
      this study, norepinephrine (NE) and epinephrine (EPI) were found to be toxic to
      oligodendrocyte (OL) cultures derived from adult rat brain. The catecholamine
      toxicity, reproduced by equimolar concentrations of H2O2, could be completely
      prevented by simultaneous treatment of OLs with the H2O2-decomposing enzyme
      catalase. These results implicate H2O2 produced by metabolism of NE and EPI as
      the toxic intermediate. Since OLs in vivo are not normally susceptible to the
      toxicity of catecholamine neurotransmitter molecules, we sought to examine the
      involvement of another cell type closely apposed to OL, that is astrocytes, as a
      protectant against catecholamine toxicity. When adult rat OLs were seeded onto a
      monolayer of neonatal rat astrocytes, the toxicity of NE, EPI and H2O2 to OLs was
      completely prevented; medium conditioned by astrocytes did not prevent the
      manifestation of H2O2 toxicity on OLs. We conclude that the OL-myelin complex is
      vulnerable to free radical-mediated damage, especially when the protective
      functions of astrocytes are impaired.

PMID- 8137176
TI  - A facilitatory role of vasopressin in hypoxia/hypoglycemia-induced impairment of
      dopamine release from rat striatal slices.
AB  - The excitatory amino acid, glutamate plays a crucial role in the pathogenesis of
      brain damage caused by anoxia and/or hypoglycemia. Although vasopressin (VP) also
      acts as an excitatory transmitter in the CNS, little is known about its effect on
      hypoxic and/or ischemic brain damage. In this study, we investigated the effect
      of arginine vasopressin (AVP) on hypoxia/hypoglycemia-induced impairment of
      dopamine release from striatal slices. Striatal slices were incubated in hypoxia
      /hypoglycemia-inducing medium with or without AVP (0.01-1.0 microM) for 20 min.
      After 1-3 h of washout in normal medium, high K(+)-evoked dopamine release from
      the slices were examined. Hypoxia/hypoglycemia-induced decrease of striatal
      dopamine release was reversed by the removal of Ca2+ in the medium, but not by
      VP1- or VP2-receptor antagonist. In contrast, AVP potentiated the
      hypoxia/hypoglycemia-induced decrease of dopamine release in the striatum. This
      AVP-induced deterioration of the striatal response was antagonized by VP2
      receptor antagonist, but not by VP1 receptor antagonist. The present results
      suggest that AVP may play a facilitatory role in hypoxia/hypoglycemia-induced
      dopamine release deficit mediated through the activation of VP2 receptor.

PMID- 8137177
TI  - Effects of predegeneration on nerve regeneration through silicone Y-chambers.
AB  - The effects of nerve predegeneration on the preferential growth of regenerating
      axons were studied using a silicone Y-chamber model. This system provided a
      choice for axons to grow towards two distal nerve options, either a 7-day
      predegenerated nerve segment (PNS) or a fresh nerve segment (FNS). The rat
      peroneal or tibial nerve was inserted into the proximal intlet and the PNS and
      FNS of the corresponding nerve were inserted into the distal outlets. At 28 days
      postoperative, the size of the distal regenerate was significantly greater (26%)
      towards the PNS for the tibial nerve group. The density and number of regenerated
      myelinated axons in the distal nerve segment was greater on the PNS for both the
      tibial (97 and 88%, respectively) and peroneal (221 and 221%, respectively) nerve
      groups. In contrast, the elevated density and number of nonvascular nuclei was
      relatively constant for both PNS and FNS. Immunocytochemical and ultrastructural
      evidence support the hypothesis that the early activation of Schwann cells is
      primarily responsible for the enhanced regeneration and maturation observed in
      PNS. It is suggested that PNS might improve the outcome after clinical repair of
      injured peripheral nerves.

PMID- 8137178
TI  - [A decade of continuing medical education in France (1983-1993)].
AB  - Continuing education is not compulsory to medical doctors in France. However,
      nearly all of them make use of several means for knowledge and practice
      refreshment. Medical journals are the first rank, both for GP's and specialists.
      The two groups behave differently as concerns the other means. Medical
      specialists who, in France, can practice outwith or within hospitals, have their
      continuing education closely related to public hospitals. GP's prefer in general
      to base their own on means which are not related to hospitals: sessions organized
      by the profession, visitors from pharmaceutical firms... etc... There is a broad
      discrepancy between the use of an educational mean and its rating as first
      priority. However, as far as French GP's are concerned, medical journals and
      sessions organized by the profession are at the first rank both for utilization
      frequency and priority rating. Visitors from pharmaceutical firms are not rated
      at first priority--although they have a very high utilization frequency--but they
      obtain an interesting second rank rating. Age, sex and workload have each an
      effect on priority rating. In many cases, survey findings are not in line with
      conventional thinking on the matter.

PMID- 8137179
TI  - [Prospects of the cost of AIDS-related death in France (1970-2020)].
AB  - Levels of seropositivity prevalence, estimated by the Brunet-Valleron report, are
      projected through the year 2020 on the basis of 4 scenarios. Cost of AIDS-related
      deaths is composed of 2 elements: (i) the indemnification to the victims of blood
      transfusion; (ii) the loss of years of life of the victims. The annual cost of
      AIDS-related deaths in France can be estimated between 10 and 12 billion in 1989
      and between 18 and 20 billion in 1992. Beyond the year 2000, the trend varies
      according to the development of the epidemic. The cumulated cost of AIDS-related
      deaths during the 90's will be 10 to 40 times higher than the simple amount of
      indemnification paid to the victims of blood transfusion.

PMID- 8137180
TI  - Collaboration in research and development between the university and the health
      services organizations.

PMID- 8137181
TI  - Who should practise? Where?

PMID- 8137183
TI  - Tobacco tax controversy.

PMID- 8137182
TI  - To warn or not to warn.

PMID- 8137184
TI  - Too many prescriptions?

PMID- 8137185
TI  - Testing penicillin allergy.

PMID- 8137186
TI  - Hemodialysis in Canada: a first-class medical crisis.

PMID- 8137187
TI  - Writing papers and changing minds.

PMID- 8137188
TI  - Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein
      thrombosis after total hip replacement.
AB  - OBJECTIVE: To compare the efficacy and cost-effectiveness of enoxaparin, a low
      molecular-weight heparin derivative, with that of low-dose warfarin in the
      prevention of deep-vein thrombosis (DVT) after total hip replacement. DATA
      SOURCES: English-language articles on enoxaparin and warfarin prophylaxis is
      patients undergoing total hip replacement published from January 1982 to December
      1992. STUDY SELECTION: Four trials of enoxaparin (involving 567 patients) and six
      trials of warfarin (involving 630) met the following criteria: randomized
      controlled trial, prophylaxis started no later than 24 hours after surgery and
      continued for at least 7 days, warfarin dose monitored and adjusted
      appropriately, enoxaparin dosage 30 mg twice daily, and DVT confirmed by
      bilateral venography. DATA EXTRACTION: Rates of DVT, cost of prophylaxis,
      diagnosis and treatment per patient, rate of pulmonary embolism (PE), number of
      deaths and incremental cost-effectiveness (cost per life-year gained). DATA
      SYNTHESIS: The pooled rate of DVT was 13.6% with enoxaparin (95% confidence
      interval [CI] 10.9% to 16.3%) and 20.6% with warfarin (95% CI 17.4% to 23.8%). At
      a cost of $19.55 per day for enoxaparin the total cost per patient, including
      prophylaxis and management of DVT, exceeded that per patient receiving warfarin
      by about $121. For every 10,000 patients treated the use of enoxaparin will
      prevent 47 cases of DVT, 3 cases of PE and 4 deaths. Thus, the estimated
      incremental cost-effectiveness of enoxaparin is $29 120 per life-year gained.
      CONCLUSION: On the basis of current Canadian cost-effectiveness guidelines the
      results of this study would be considered moderate to strong evidence to adopt
      enoxaparin prophylaxis against DVT after total hip replacement. However, because
      of the limited data the estimates are uncertain. Future trials should compare
      enoxaparin and warfarin and incorporate a prospective economic appraisal.

PMID- 8137189
TI  - Measles outbreak in 31 schools: risk factors for vaccine failure and evaluation
      of a selective revaccination strategy.
AB  - OBJECTIVE: To examine the risk factors for measles vaccine failure and to
      evaluate the effectiveness of a selective revaccination strategy during a measles
      outbreak. DESIGN: Matched case-control study. SETTING: Thirty-one schools in
      Mississauga, Ont. SUBJECTS: Eighty-seven previously vaccinated school-aged
      children with measles that met the Advisory Committee on Epidemiology's clinical
      case definition for measles. Two previously vaccinated control subjects were
      randomly selected for each case subject from the same homeroom class.
      INTERVENTIONS: All susceptible contacts were vaccinated, and contacts who had
      been vaccinated before Jan. 1, 1980, were revaccinated. When two or more cases
      occurred in a school all children vaccinated before 1980 were revaccinated. MAIN
      OUTCOME MEASURES: Risk of measles associated with age at vaccination, time since
      vaccination, vaccination before 1980 and revaccination. RESULTS: Subjects
      vaccinated before 12 months of age were at greater risk of measles than those
      vaccinated later (adjusted odds ratio [OR] 7.7, 95% confidence interval [CI] 1.6
      to 38.3; p = 0.01). Those vaccinated between 12 and 14 months of age were at no
      greater risk than those vaccinated at 15 months or over. Subjects vaccinated
      before 1980 were at greater risk than those vaccinated after 1980 (adjusted OR
      14.5, 95% CI 1.5 to 135.6). Time since vaccination was not a risk factor.
      Revaccination was effective in reducing the risk of measles in both subjects
      vaccinated before 1980 and those vaccinated after 1980 (adjusted OR reduced to
      0.6 [95% CI 0.1 to 5.3] and 0.3 [95% CI 0.13 to 2.6] respectively). However, only
      18 cases were estimated to have been prevented by this strategy. CONCLUSIONS:
      Adherence to routine measles vaccination for all eligible children is important
      in ensuring appropriate coverage with a single dose. The selective revaccination
      strategy's high labour intensiveness and low measles prevention rate during the
      outbreak bring into question the effectiveness of such a strategy.

PMID- 8137190
TI  - Dialysis utilization in the Toronto region from 1981 to 1992. Toronto Region
      Dialysis Committee.
AB  - OBJECTIVE: To analyse trends in the demand for and supply of dialysis in the
      Toronto region and to determine whether planned dialysis expansion will be
      sufficient to provide for the projected growth of the dialysis population.
      DESIGN: Descriptive analysis of data reported to the Toronto Region Dialysis
      Registry between 1981 and 1992, compared with provincial and national
      equivalents. SETTING: All secondary and tertiary care dialysis programs in the
      Toronto region participating in the registry. PATIENTS: All 504 existing patients
      enrolled in dialysis programs in 1981 and all 3794 new patients entering programs
      from 1982 to 1992. Patients with acute renal failure were excluded. MAIN OUTCOME
      MEASURES: Demand for dialysis: dialysis population at year end, age distribution,
      crude mortality rate and transplant rate. Supply of resources: distribution of
      modality (hemodialysis or peritoneal dialysis), number of patients treated per
      hemodialysis station, number of hemodialysis stations per million population and
      hemodialysis utilization index (actual/budgeted treatments). RESULTS: During the
      study period the number of dialysis patients in the Toronto region went from 504
      to 1422, for an increase of 182.1%. The average rate of growth was 9.8% per year.
      Of the total increment of 918 patients from 1981 to 1992, 390 (42.5%) were 65
      years of age or more; none the less, the average annual crude mortality rate
      remained relatively constant, at 13.8% to 17.3%. The transplantation rate
      declined from a peak of 20.2% in 1982 to 7.8% in 1992. During the study period
      the Toronto region had much higher numbers of dialysis patients, and hemodialysis
      patients, per hemodialysis station than the rest of Ontario or Canada. The
      region's hemodialysis utilization index was 101% in 1991 and 102% in 1992; the
      index in individual hospitals varied from 98% to 124% (85% was considered
      optimal). CONCLUSIONS: The growth of the dialysis population in the Toronto
      region has caused a critical shortage of resources. This trend can be attributed
      mainly to a decrease in the transplantation rate and an increase in the number of
      elderly patients entering dialysis programs, combined with insufficient funding
      for expansion of facilities. Continuation of this trend would be expected to
      limit universal access to this expensive, but life-sustaining therapy.

PMID- 8137192
TI  - Genome projects: bridging into the future.

PMID- 8137193
TI  - Guide helps FPs treat patients with HIV disease.

PMID- 8137191
TI  - Temporal trends in breast cancer surgery in Ontario: can one randomized trial
      make a difference?
AB  - OBJECTIVE: To assess the effect of a single randomized clinical trial, the
      National Surgical Adjuvant Breast Project (NSABP) B-06, on the surgical
      management of breast cancer in women. DESIGN: Retrospective cohort study.
      SETTING: All hospitals in Ontario. PATIENTS: A consecutive sample of 37,447 women
      with breast cancer newly diagnosed from Jan. 1, 1980, to Dec. 31, 1989, linked to
      a surgical procedure record in the Ontario Cancer Registry. MAIN OUTCOME MEASURE:
      The most invasive surgical procedure used within 90 days of diagnosis. RESULTS:
      Unilateral breast-ablative surgery (BAS) was performed in 57.3% of the women and
      breast-conserving surgery (BCS) in 31.6%. The annual rate of BAS declined from
      77.5% in 1980 to 44.2% in 1989 and the rate of BCS rose from 12.5% in 1980 to
      43.5% in 1989. The decline was linear from 1980 to 1984 and then accelerated
      significantly in 1985 (p < 0.0001), after the results of the NSABP B-06 trial
      were published. CONCLUSION: One randomized clinical trial can have an immediate
      and profound effect on medical practice.

PMID- 8137194
TI  - Dalhousie medical school's artist-in-residence uses unique methods to interpret
      brain's mysteries.

PMID- 8137195
TI  - Canada's community pharmacists feel threatened from several directions.

PMID- 8137196
TI  - The plan to prevent harassment and discrimination in Ontario universities: why
      all the fuss?

PMID- 8137197
TI  - Group of Alberta physicians calls for major hikes in patients' medicare bills.

PMID- 8137198
TI  - Medical researchers strut their stuff at Atlantic Canada's first pharmaceutical
      showcase.

PMID- 8137199
TI  - Toronto hospital a real-life experiment in dealing with health care's new fiscal
      realities.

PMID- 8137200
TI  - Identifying risk factors for disease no guarantee patients will modify behavior,
      conference told.

PMID- 8137201
TI  - A randomized study of chemotherapy, radiation therapy, and surgery versus surgery
      for localized squamous cell carcinoma of the esophagus.
AB  - BACKGROUND: Despite well-established surgical approaches, the prognosis for
      patients with squamous cell carcinoma of the esophagus remains dismal. To assess
      the benefit of adjuvant chemotherapy and radiation therapy (CRT), a randomized
      trial with and without sequential preoperative CRT was undertaken; CRT combined
      20 Gy and two courses of 5-FU and cisplatin. METHODS: Patients were included on
      the basis of the following criteria: squamous cell carcinoma of the esophagus,
      younger than 70 years of age, World Health Organization status below 2, estimated
      survival time greater than 3 months, and no previous treatment for the cancer.
      Patients were not included if they had experienced a loss in body weight greater
      than 15% or had tracheoesophageal fistula, metastases, or uncontrollable
      infection. RESULTS: Eighty-six patients thus fulfilled the criteria for inclusion
      (41 CRT, 45 non-CRT). The groups were well-matched for age, sex, tumor location,
      size, and grade. Operative mortality was 8.5% and 7%, respectively, for each
      group with a 27-day hospital stay for both groups. Long-term survival was not
      significantly different, with 47% of both groups alive at 1 year. CONCLUSIONS:
      The authors concluded that this neoadjuvant treatment did not change operative
      mortality or survival time for patients with squamous cell carcinoma of the
      esophagus.

PMID- 8137202
TI  - Expression of c-myc mRNA as an aid in histologic differentiation of adenoma from
      well differentiated adenocarcinoma in the stomach.
AB  - BACKGROUND: Using prospective follow-up studies, the authors examined the value
      of the expression of c-myc mRNA in biopsy specimens obtained from elevated
      gastric lesions as an aid in the differentiating between adenomas and well
      differentiated elevated-type adenocarcinomas. METHODS: By in situ hybridization,
      the authors determined the expression of c-myc mRNA in biopsy specimens of
      elevated gastric lesions. The 31 patients who had borderline lesions with and
      without overexpression of c-myc were followed with repeated endoscopic
      examinations and gastric biopsies. RESULTS: Endoscopic follow-up examinations
      showed that gastric cancer was detected in 5 of 11 patients (46%) with elevated
      lesions that stained positively for c-myc mRNA during an observation period of 15
      months (range, 2-32 months). The cancers were confirmed histologically in
      gastrectomy specimens. No cancers were found in patients with elevated lesions
      that stained negatively. The difference was statistically significant (P < 0.01).
      CONCLUSIONS: The overexpression of c-myc mRNA may present a new tool for
      distinguishing between adenomas and well differentiated adenocarcinomas of the
      elevated type.

PMID- 8137203
TI  - Treatment of liver metastases from colorectal cancer with radioactive implants.
AB  - BACKGROUND: Long-term survival and possible cure can be achieved in selected
      patients after resection of liver metastases from a colorectal primary tumor. In
      this study, the authors used radioactive implants as adjunctive therapy for
      patients who had incomplete resections of liver metastases. METHODS: From 1979 to
      1990, 17 implants were performed in 12 patients (median age, 61 years).
      Brachytherapy was performed for microscopically positive margins in 7 implants
      and for gross residual disease in 10 implants. Volume implants were performed for
      gross residual disease using 125I seeds, with a median matched peripheral dose of
      160 Gy. Most of the implants for microscopic residual disease were planar
      implants with 125I suture seeds, with a median treatment dose of 150 Gy. RESULTS:
      There were no serious postoperative complications. Overall median survival was 18
      months, and 42% of patients survived 2 years or more. Extrahepatic metastases
      occurred in 83% of patients (10 of 12). Intrahepatic failure close to the
      implanted site occurred in 42% of patients (5 of 12), and intrahepatic failure
      anatomically remote from the implant site occurred in 25% (3 of 12). CONCLUSIONS:
      This approach is feasible and achieves reasonable local control of residual
      disease after resection of hepatic metastases from colorectal cancer. The
      anatomic pattern of failure supports efforts to intensify local therapy and to
      address the high rate of distant metastases.

PMID- 8137204
TI  - The importance of patient selection for adjunctive postoperative radiation
      therapy for cancer of the rectum. Patient selection in adjunctive therapy.
AB  - BACKGROUND: Clinical stage of disease is an important selection criterion for
      choice of primary treatment and strategies for adjunctive therapy for most
      cancers. For adenocarcinoma of the rectum, strategies for adjuvant treatment are
      based primarily on pathologic stage alone, without consideration of presenting
      clinical factors. This analysis was undertaken to assess the effect of patient
      selection on results of adjunctive therapy. METHODS: Three groups of patients
      with Astler-Coller Stage B2 and C rectal cancer were compared to assess the
      effect of patient selection factors on outcome of treatment after adjuvant
      postoperative radiation. Thirty-two patients in Group 1 received only 5 Gy
      preoperatively; 54 patients in Group 2 received low-dose (5 Gy) preoperative and
      high-dose (45 Gy) postoperative radiation; and 53 patients in Group 3 received
      high-dose (45 Gy) postoperative radiation. All patients have a minimum follow-up
      of 5 years. Whereas Group 1 and Group 2 patients were similar in distribution by
      clinical tumor characteristics, Group 3 had more patients with poor clinical
      features: higher median age, more men, and a higher proportion of tumors in the
      distal rectum. Group 3 also had a slightly higher percentage of C2 tumors
      compared with the other two groups. RESULTS: Treatment was well tolerated with
      minimal side effects. Patients in Group 1 had no long-term complications. Four
      percent of patients (2 of 54) in Group 2 and 6% of patients (3 of 53) in Group 3
      experienced major small bowel complications. The incidence of local recurrence
      was 34% (11 of 32) in Group 1, 9% (5 of 54) in Group 2, and 21% (11 of 53) in
      Group 3. The incidence of distant metastasis was 28% (9 of 32), 22% (12 of 54),
      and 38% (20 of 53), respectively. Absolute 5-year survival rates were 54%, 72%,
      and 41% in these three groups, respectively. CONCLUSIONS: Low-dose preoperative
      adjunctive radiation alone (Group 1) resulted in a high incidence of local
      recurrence and poor survival compared with patients treated more appropriately
      with low-dose preoperative plus adjunctive postoperative irradiation (Group 2).
      In spite of postoperative radiation, patients with clinically unfavorable rectal
      cancer (Group 3) did worse than carefully selected patients, although both were
      nominally Stage B2 and C. Careful patient selection before surgery,
      histopathologic stage of disease postsurgery, and adequate adjunctive therapy are
      all important factors in obtaining the best results from adjunctive therapy.

PMID- 8137205
TI  - Prognostic factors in pulmonary fibrohistiocytic lesions.
AB  - BACKGROUND: The spectrum of pulmonary fibrohistiocytic lesions (PFL) ranges from
      benign fibrohistiocytoma or inflammatory pseudotumor, fibrohistiocytic type (IP),
      to fibrohistiocytic lesions of borderline malignant appearance (B), to
      unequivocal malignant fibrous histiocytoma (MFH). The authors reviewed a spectrum
      of PFL in an attempt to define their natural history and establish independent
      factors of prognostic significance. METHODS: Thirty-one fibrohistiocytic lesions
      were analyzed by multiple clinical, gross, and microscopic factors. Prognostic
      factors were evaluated by univariate and multivariate Cox proportional hazards
      models. RESULTS: After histopathologic review, the cases were classified into IP
      (15 cases), B (3 cases), and MFH (13 cases). IP tended to occur in younger
      patients (median age, 30 years; range, 11-64 years) than did MFH (median age, 54
      years; range, 12-81 years) (P = 0.03). All 15 patients with IP and 3 patients
      with B survived. Local recurrence developed in 2 patients with IP and 6 patients
      with MFH. Distant metastases occurred in 7 patients with MFH. Eight of 13
      patients with MFH died of disease, with a median survival time of 16 months
      (range, 6-36). For all pulmonary fibrohistiocytic lesions, univariate Cox
      regression analysis disclosed several statistically significant prognostic
      factors associated with mortality: metastasis (P = 0.0005), significant necrosis
      (P = 0.0015), local recurrence (P = 0.003), bizarre giant cells (P = 0.0282),
      mitoses greater than or equal to 3 per 50 high-power fields (P = 0.0286), stage
      at surgery (P = 0.002), high cellularity (P = 0.0267), and poor circumscription
      (P = 0.0294). Other parameters (age, sex, symptoms, laterality, location,
      atypical mitoses, nuclear pleomorphism, degree of fibrosis, and size) were not
      significant prognostic factors. By multivariate Cox regression analysis,
      metastasis was the most significant individual parameter (P = 0.002), overriding
      all other prognostic factors. With metastasis removed from the model, local
      recurrence (P = 0.0199) and necrosis (P = 0.037) were the other significant
      independent prognostic factors. CONCLUSIONS: Certain individual clinical, gross,
      and microscopic features have prognostic relevance in determining survival time
      in pulmonary fibrohistiocytic lesions.

PMID- 8137206
TI  - Asbestos and nonasbestos fiber content in lung tissue of Japanese patients with
      malignant mesothelioma.
AB  - BACKGROUND: Pulmonary fiber content of both asbestos and nonasbestos types were
      evaluated in Japanese patients with malignant pleural mesotheliomas. METHODS:
      Pulmonary fiber content was analyzed in 16 patients and 16 case-matched control
      subjects by transmission electron microscopy with energy-dispersive X-ray
      analysis using a low-temperature ashing procedure. RESULTS: The geometric mean
      content of total asbestos was significantly higher in the patients (22.0 x 10(6)
      fibers/g dry lung) than in the control subjects (2.24 x 10(6) fibers/g dry lung)
      (P < 0.01). When the asbestos content was analyzed by fiber type, the geometric
      means were also consistently and significantly higher among the patients compared
      with the control subjects (P < 0.01). Results were as follows: (1) amosite:
      patients 3.94 times 10(6) versus control subjects 0.23 x 10(6); (2) crocidolite:
      patients 3.56 times 10(6) versus control subjects 0.35 times 10(6); (3) total
      amphiboles: patients 16.0 times 10(6) versus control subjects 0.77 times 10(6);
      and (4) chrysotile: patients 3.76 times 10(6) versus control subjects 1.01 times
      10(6). However, when individual total asbestos content was considered, 7 of the
      16 patients (44%) had levels lower than the highest value noted among the control
      subjects. Pulmonary fiber content of patients and control subjects also revealed
      the presence of nonasbestos fibers. The geometric mean of nonasbestos fibers was
      significantly higher in the patients (87.3 x 10(6)) than in control subjects
      (33.8 x 10(6)) (P < 0.01). The major type of nonasbestos fibers in both groups
      was aluminum silicates. The mean of ratios of nonasbestos fiber contents to total
      asbestos contents in the patients and control subjects was 7.0 and 17.3,
      respectively. CONCLUSIONS: The results were mainly in agreement with the findings
      of earlier investigations, but fiber content of both chrysotile and nonasbestos
      fiber as well as those of amphibole asbestos were significantly higher in the
      patients than in the control subjects.

PMID- 8137207
TI  - Breast cancer diagnosis by lactate dehydrogenase isozymes in nipple discharge.
AB  - BACKGROUND: The diagnosis of breast cancer based on nipple discharge, often the
      only clinical manifestation of early breast cancer, is currently unsatisfactory.
      Because M subunits of lactate dehydrogenase (LDH) have been noted to increase in
      cancer tissue, the author assessed the value of using LDH isozyme patterns in
      nipple discharge for the diagnosis of breast cancer. METHODS: LDH isozyme levels
      in (1) nipple discharge of patients diagnosed as having breast cancer,
      intraductal papilloma, mastopathy, drug-induced nipple discharge, mastitis, or
      benign nipple discharge; (2) control samples of normal nipple discharge (milk) 6
      days, 1-5 months, and 6 months to 2 years postpartum; (3) the serum of patients
      presenting with nipple discharge; and (4) normal and cancerous breast tissue
      extracts were measured using a Ciba-Corning LDH isozyme system (Ciba Corning
      Diagnostic Corp., Tokyo, Japan). RESULTS: LDH isozyme levels in the nipple
      discharge of patients with benign breast diseases displayed various patterns.
      Levels in the nipple discharge of patients with breast cancer, including
      noninvasive carcinoma, tended to increase in ascending order from LDH1 to LDH5.
      This pattern was similar to that in breast cancer tissue and was unrelated to the
      pattern in serum. CONCLUSION: LDH isozyme assay of nipple discharge may be a
      useful technique for providing a supporting diagnosis of breast cancer.

PMID- 8137209
TI  - Trends in cervical cancer incidence among young black and white women in
      metropolitan Detroit.
AB  - BACKGROUND: Although the overall incidence of invasive cervical cancer in the
      United States has declined over the past several decades, recent studies suggest
      that rates for both invasive and in situ cervical cancer are rising among younger
      women. METHODS: Trends in cervical cancer incidence among females between the
      ages of 15 and 39 years were evaluated using data from the Metropolitan Detroit
      Cancer Surveillance System, a population-based registry and founding participant
      in the SEER Program of the National Cancer Institute. Age-adjusted and age
      specific rates for all black and white women in this age group were evaluated as
      well as rates for married and single women for the period 1973-1991. RESULTS:
      Incidence trends vary by race and marital status. A nonlinear increasing trend
      was evident (P < 0.01), for in situ cervical cancer among white women, with rates
      for single white women exhibiting the largest increase. Rates among black women
      for in situ cervical cancer exhibited a nonlinear decreasing trend (P < 0.01),
      with rates for married black women declining by 75%. Among single white women,
      invasive cervical cancer exhibited an increasing linear trend (P < 0.01),
      although the number of cases was small. CONCLUSIONS: Differences in trends among
      black and white women may reflect a combination of greater exposure to risk
      factors associated with cervical carcinoma as well as differential access to
      diagnostic and treatment services. Appropriate groups should be targeted for
      educational, screening, and follow-up services.

PMID- 8137208
TI  - High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer.
AB  - BACKGROUND: The authors evaluated a high-intensity inpatient regimen using
      augmented but subtransplantation doses of multiple agents in patients with
      metastatic breast cancer. Two high-dose courses were given in an attempt to
      improve the efficacy of high-dose regimens using a single course. METHODS: Forty
      women received treatment between October 1988 and October 1991. The median age
      was 38 years (range, 24-56 years). Twenty-five patients were receiving their
      first chemotherapy for metastatic disease; 15 patients had received one or more
      prior regimens. The patients received two courses of chemotherapy, which
      consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on
      days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v.
      on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10
      (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin
      15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate.
      Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in
      14 patients who had received prior doxorubicin. RESULTS: Twenty-nine of 40
      patients (73%) had objective response to therapy, with 10 (25%) complete
      responses. Four patients who obtained a complete response remain disease-free at
      14, 21, 28, and 32 months, respectively; all of these patients received this
      regimen as first-line therapy for metastatic disease. Myelosuppression was
      severe, with median durations of leukocytes less than 1000/microliters and
      platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days
      (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of
      68 courses. Four patients (10%) had treatment-related deaths. CONCLUSIONS: This
      regimen produced high overall response and complete response rates compared with
      standard regimens. However, only 15% of patients who received this therapy as
      first-line treatment for metastatic breast cancer remain disease-free, and median
      response duration was shorter than that reported using high-dose therapy with
      bone marrow support. Toxicity with this regimen was greater than anticipated,
      although myelosuppression and stomatitis would be reduced by the use of
      cytokines. This regimen does not improve results achieved with standard therapy
      sufficiently to justify its toxicity and expense.

PMID- 8137210
TI  - OVX1 as a marker for early stage endometrial carcinoma.
AB  - BACKGROUND: Endometrial carcinoma is generally diagnosed only after the onset of
      postmenopausal bleeding. Although most patients with Stage I disease can be
      cured, the prognosis worsens significantly when the tumor is no longer confined
      to the uterine corpus. Serum CA 125 is elevated in only 10-20% cases of Stage I
      and II endometrial carcinoma. A serum tumor marker that can detect early stage
      endometrial cancer might aid in management of the disease. METHODS: An OVX1
      double-determinant radioimmunoassay was used to detect an epitope on a high
      molecular-weight mucinlike glycoprotein found in the sera of 45 patients with
      endometrial cancer. RESULTS: Apparently healthy persons had serum OVX1 antigen
      levels of 2.23 plus or minus 2.48 U/ml (mean +/- standard deviation). Elevated
      levels of OVX1 antigen (> 7.2 U/ml) were found in 5% of 184 healthy persons and
      in 64% of 45 patients with endometrial cancer. OVX1 antigen was elevated in 64%
      of 36 patients with Stage I, 50% of 2 patients with Stage II, 60% of 5 patients
      with Stage III, and each of 2 patients with Stage IV endometrial cancer, but only
      8.6% of 58 patients with endometriosis. Elevation of serum OVX1 was found more
      frequently in patients with deep myometrial invasion and with poorly
      differentiated tumors (P < 0.01). CONCLUSIONS: The OVX1 antigen deserves further
      evaluation as a marker for early detection of endometrial cancers and as a
      prognostic factor for women with apparent early stage disease.

PMID- 8137211
TI  - Early de novo ovarian carcinoma. A study of fourteen cases.
AB  - BACKGROUND: The search for methods of early detection of ovarian carcinoma in
      recent years has emphasized the lack of information regarding the histologic
      features of early carcinoma or its precursor lesions; few examples of early de
      novo ovarian carcinoma have been reported. METHODS: The clinicopathologic
      features of 14 cases of early ovarian carcinoma detected as microscopic findings
      in grossly normal ovaries retrieved from a consultation practice and the files of
      the Massachusetts General Hospital were reviewed. RESULTS: The patients ranged in
      age from 27-65 years (mean, 50 years). Three women had a family history of
      ovarian carcinoma and six did not. The tumors ranged from microscopic to 7 mm in
      greatest dimension; all were unilateral and four were multifocal. One tumor
      involved the surface and its crypts; four, the surface and superficial cortex;
      eight, the superficial cortex only; and in one, surface involvement was not
      ascertainable. Ten carcinomas were serous; one, endometrioid; one, clear cell;
      and two, poorly differentiated, of undetermined cell type. Severe atypia of the
      noncarcinomatous surface epithelium or its inclusion cysts was additionally
      present in three cases. Among the seven patients whose diagnoses were made at the
      time of oophorectomy who had follow-up data of at least 2 years or until
      recurrence or death, five were alive without recurrences, one was alive with
      recurrence, and one died of tumor. Two of the three women died whose ovarian
      tumors were diagnosed retrospectively on discovery of subsequent peritoneal
      carcinomatosis, and the third was alive with recurrent tumor. No relation between
      any clinical or pathologic feature and survival was apparent in this small series
      except for a suggestion that well differentiated tumors had a good prognosis.
      CONCLUSIONS: These findings document that at least a subset of ovarian epithelial
      cancers develops de novo. The guarded prognosis associated with these tumors
      despite their minute dimensions raises questions about the value of current
      screening techniques for early detection of ovarian cancer.

PMID- 8137212
TI  - Intraperitoneal mitoxantrone as consolidation treatment for patients with ovarian
      carcinoma in pathologic complete remission.
AB  - BACKGROUND: Stages II-IV ovarian cancer in pathologic complete remission (pCR) at
      second-look surgery have a high relapse rate (50%) during the first 2 years.
      Considering relapse sites (abdomen and/or pelvis), intraperitoneal (IP) therapy
      is a logical approach. Mitoxantrone is an effective drug against ovarian cancer
      cells in vitro and is an attractive agent for IP therapy because of its very low
      peritoneal clearance. The value of IP mitoxantrone was studied as consolidation
      treatment of ovarian cancer in pCR at second-look surgery. METHODS: Fifty
      patients with Stages II-IV ovarian cancer (8, Stage II; 37, Stage III; 5, Stage
      IV) were included in this Phase II study, which began in June 1988. All patients
      had undergone initial cytoreductive surgery followed by 6 cyclophosphamide,
      doxorubicin, and cisplatin cycles. All patients were in pCR, as confirmed by
      second-look surgery. Consolidation treatment consists of 20 mg (total dose per
      cycle) IP mitoxantrone every 3 weeks for six cycles. RESULTS: Toxicity was
      limited to mild abdominal pain not requiring dose reduction (90% pain grade < or
      = 2). With a median follow-up of 2 years, the 5-year predicted survival is 59.8%
      (95% confidence interval [CI], 48.3 - 71.3), and the disease-free survival (DFS)
      rate is 47.3% (95% CI, 36.7 - 57.9). Patients with no or microscopic residual
      disease after initial surgery had a better 5-year DFS rate (75.8%) than those
      with macroscopic residual disease (31.2%) (P = 0.01). CONCLUSION: IP mitoxantrone
      (20 mg/cycle) is feasible with an acceptable abdominal toxicity. The results in
      terms of DFS are encouraging, but a randomized study versus no treatment is
      necessary to prove the value of this consolidation treatment.

PMID- 8137213
TI  - Flow cytometric DNA ploidy and S-phase heterogeneity in advanced ovarian
      carcinoma.
AB  - BACKGROUND: The prognostic significance of flow cytometric DNA ploidy and S-phase
      fraction (SPF) in ovarian cancer has been controversial. In the current study,
      the authors analyzed tumor heterogeneity in respect to DNA index DI and SPF.
      METHODS: Flow cytometric variation in DI and SPF among representative fresh tumor
      material from the primary tumor, metastasis, and malignant effusions from the
      same patient was analyzed. RESULTS: One hundred thirty-two samples from 47
      patients were analyzed, and 119 samples from 42 patients were evaluable. Stable
      DI between different samples was found in 34 patients, whereas heterogeneity was
      found in 8 patients (19%). The metastases showed stable DNA content. The
      malignant effusion samples often lacked tumor cells. The representative ones were
      often DNA diploid. In 21% of the aneuploid samples, the SPF could not be
      analyzed. In 38% of the aneuploid samples, the stem line constituted less than
      15% of measured nuclei. In these samples, a negative correlation between SPF and
      percentage of aneuploid cells was found, making SPF unreliable. Correct SPF
      measurement was thus possible in only 41% of the aneuploid samples, and in these
      tumors, SPF values varied considerably among different samples from the same
      patient, illustrated by a median SPF difference of 11% (range, 0-28%).
      CONCLUSIONS: Tumor DI heterogeneity existed in 19% of tumors. SPF depended on the
      amount of aneuploid cells in case of small stem lines and varied considerably,
      making its use as a prognostic factor doubtful. To ensure that all tumor stem
      lines are represented, at least two biopsy specimens from any solid tumor should
      be analyzed.

PMID- 8137214
TI  - Human parathyroid hormone-related protein in ovarian small cell carcinoma. An
      immunohistochemical study.
AB  - BACKGROUND: Small cell carcinomas (SCC) are the most common ovarian tumors
      associated with hypercalcemia. Parathyroid hormone-related protein (PTHrp) is the
      most frequent cause of hypercalcemia of malignancy. METHODS: The presence of
      PTHrp in SCC has been studied by immunohistochemistry in formalin fixed, paraffin
      embedded tissues. A polyclonal antibody against a synthetic peptide corresponding
      to the first 36-N terminal amino acid residues of PTHrp was used. Normal dog
      skin, which is rich in PTHrp, was used as a positive control. Absorption tests
      using the synthetic peptide as antigen were done in all the cases. RESULTS:
      Immunoreactivity for PTHrp was found in five of seven cases of SCC. The serum
      calcium levels were elevated in two of these cases, normal in two, and unknown in
      one. The two negative cases were associated with high serum calcium levels.
      CONCLUSION: The lack of correlation between immunoreactivity and serum calcium
      levels can be explained on the basis that immunohistochemistry is dependent on
      the peptide content of cells rather than on the capability for hormone production
      and/or release. The results suggest that PTHrp plays a role in the development of
      hypercalcemia in patients with SCC of the ovary.

PMID- 8137215
TI  - Interleukin-6 level in serum and ascites as a prognostic factor in patients with
      epithelial ovarian cancer.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that can be
      produced by human ovarian cancer cells. Elevated IL-6 levels have been found in
      the serum and ascites of patients with ovarian cancer, but its role in this
      disease has not been clearly established. METHODS: The authors studied the
      relationship between IL-6 levels in serum and ascites, various tumor parameters,
      and survival in 70 patients with newly diagnosed, untreated epithelial ovarian
      cancer. Ascites and serum specimens were obtained at the time of initial surgery,
      and IL-6 levels were determined using the B9 bioassay. RESULTS: All patients
      underwent platinum-based chemotherapy after initial surgery. The median age of
      the group was 62 years (range, 28-87 years), and the median follow-up time was 13
      months (range, 12-59 months). Significantly higher IL-6 levels were detected in
      patients' ascites (median, 49,612 pg/ml [range, < 1 to 680,330 pg/ml]) compared
      with serum (median, 10 pg/ml [range, < 1 to 1221 pg/ml]) (P < 0.0001). IL-6
      levels in ascites correlated significantly with the volume of ascites (P <
      0.0001) and nearly so with the size of tumor found at initial surgery (P = 0.05).
      Serum and ascites IL-6 levels did not correlate statistically with overall
      survival time, tumor stage, grade, histologic findings, residual tumor volume
      after debulking, and serum CA 125 levels. Although not statistically significant,
      patients who responded to chemotherapy tended to have lower ascites IL-6 levels
      (median, 21,102 pg/ml) compared with patients who did not respond to chemotherapy
      (median, 40,200 pg/ml). CONCLUSIONS: IL-6 is present in very high amounts in the
      ascites of patients with epithelial ovarian cancer. IL-6 levels in ascites
      correlated significantly with ascites volume and initial tumor size. IL-6 levels
      in ascites and serum did not correlate statistically with other tumor parameters
      or with survival time.

PMID- 8137216
TI  - Progressive carcinoid heart disease after resection of primary ovarian carcinoid.
AB  - Primary ovarian carcinoid tumors are uncommon, and carcinoid heart disease is a
      rare complication. Although carcinoid syndrome and carcinoid heart disease
      typically occur in the setting of metastatic carcinoid tumor, particularly
      involving the liver, this is not necessarily the case in patients with primary
      ovarian carcinoid tumors. After surgical resection of an ovarian carcinoid tumor,
      the prognosis is excellent; however, carcinoid heart disease can continue to
      progress. The following is a case report of a patient who, despite having
      complete resection of a primary ovarian carcinoid tumor, went on to develop
      progressive, debilitating carcinoid heart disease. This is an important scenario
      to recognize, because proper management and surgical intervention in carcinoid
      heart disease can be lifesaving.

PMID- 8137217
TI  - Hormonal ablation as effective therapy for carcinomatous meningitis from
      prostatic carcinoma.
AB  - BACKGROUND: Metastases to the meninges from prostatic cancer are rare, accounting
      for less than 0.5% of all solid tumor cases. Management for patients with
      leptomeningeal metastases of various histologic types includes intrathecal
      chemotherapy and radiation therapy, but the prognosis is poor. Therefore, the
      identification of selected patients for whom effective therapy exists is of
      paramount importance. METHODS: A patient with adenocarcinoma of the prostate
      presented with leptomeningeal metastases as his first manifestation of metastatic
      disease. RESULTS: Androgen blockade was initiated with flutamide and
      ketoconazole. After 5 days of therapy, leuprolide acetate depot was substituted
      for ketoconazole. The patient responded to therapy and remained asymptomatic with
      a normal serum prostate-specific antigen levels at 16-plus months with no further
      evidence of malignant cells in spinal fluid from repeated lumbar punctures.
      CONCLUSION: Patients with hormone-naive metastatic prostatic carcinoma manifested
      as carcinomatous meningitis should be considered for hormonal ablative therapy.
      This is preferred to the use of intrathecal chemotherapy, which has limited
      efficacy.

PMID- 8137218
TI  - Epidermal growth factor receptor content in human renal cell carcinomas.
AB  - BACKGROUND: The expression of epidermal growth factor receptor (EGFR) mRNA has
      been demonstrated in human renal cell carcinomas (RCC), but few reports
      quantitate EGFR in RCC and correlate EGFR content with clinicopathologic
      findings. METHODS: Using 125I-EGF as a ligand, the maximum binding of EGF in
      membrane preparations from RCC (EGFR content) was studied by Scatchard analysis.
      RESULTS: A single class of binding sites for EGF was observed in 74% of RCC and
      50% of normal renal tissues. The EGFR content was increased significantly in RCC
      compared with normal tissues. In all cases in which EGFR was undetectable, there
      was no evidence of distant metastasis, venous invasion, or regional lymph node
      involvement, and these patients had a better clinical outcome than patients with
      detectable EGFR. The EGFR content was significantly lower in nuclear Grade 1
      tumors than in tumors of higher nuclear grades. No significant difference between
      EGFR content and other clinicopathologic findings was detected. CONCLUSION: The
      determination of EGFR content in RCC may become an important prognostic factor
      for the biologic behavior of RCC.

PMID- 8137219
TI  - Results of radical cystectomy for transitional cell carcinoma of the bladder and
      the effect of chemotherapy.
AB  - BACKGROUND: Radical cystectomy continues to be one of the primary modalities of
      treatment for locally advanced bladder cancer. However, long-term survival after
      cystectomy has improved only marginally in the last decade, and still, nearly
      half of the patients die from the disease within 5 years. Adjuvant treatments
      such as radiation therapy and chemotherapy have been used, but a clear advantage
      has not been demonstrated. METHODS: The authors reviewed 130 patients who
      underwent radical cystectomy by the same surgeon as treatment for transitional
      cell carcinoma of the bladder. Morbidity, postoperative mortality, overall
      survival time, and accuracy of clinical staging as well as the effect of
      perioperative chemotherapy were evaluated. RESULTS: The overall actuarial
      survival rate at 2, 5, and 10 years was 80%, 53%, and 45%, respectively. The
      survival rate based on T-classification at 5 years was 82%, 65%, and 28% for less
      than pT2, pT2, and greater than pT2, respectively. Regional lymph node status had
      a significant effect on survival. The 5-year survival rate for all patients with
      negative nodes was 65%, whereas patients with positive nodes had a 18% 5-year
      survival rate. The overall clinical staging error was 61.5%, with 41.5% of the
      cancers understaged. Of the patients with cTis, 60% were found to be of greater
      extent than pT1 tumors. No apparent survival advantage was noted for those
      patients who received perioperative chemotherapy when compared with patients who
      were followed conservatively or received chemotherapy upon relapse. These
      results, however, are not conclusive because this was an observation study and
      the number of patients was limited. CONCLUSIONS: Only a modest improvement in
      survival time after radical cystectomy has been observed in the last decade,
      despite the use of adjuvant treatments such as radiation and chemotherapy. The
      pathologic (pT) classification is the most accurate prognostic indicator.
      Clinical errors in classification are common and impair the evaluation of
      neoadjuvant treatments. A high incidence of invasive tumors of greater extent
      than pT1 was found among patients with clinical cTis; this supports an aggressive
      approach when these patients do not respond promptly to intravesical
      chemotherapy. Prospective randomized studies are needed to evaluate objectively
      the benefit of perioperative adjuvant treatment in locally advanced transitional
      cell carcinoma of the bladder.

PMID- 8137220
TI  - Carboplatin, methotrexate, and vinblastine in the treatment of patients with
      advanced urothelial cancer. A phase II trial.
AB  - BACKGROUND: A Phase II study with carboplatin, methotrexate, and vinblastine
      (CAMV) was conducted with patients who had advanced urothelial cancer to
      investigate the activity and toxicity of carboplatin when used in combination
      chemotherapy. METHODS: Thirty-six patients with advanced urothelial cancer were
      treated with carboplatin 300 mg/m2 (day 1), methotrexate 40 mg/m2 (days 1 and 8)
      and vinblastine 4 mg/m2 (days 1 and 8) every 4 weeks. Characteristics of the
      patients were as follows: men:women, 32:4; median age, 65 years (range, 42-76
      years); and median Eastern Cooperative Oncology Group performance status, 0
      (range, 0-2). Thirty-six patients were evaluable for toxicity and 33 for
      response. RESULTS: Objective responses (OR) were achieved in 13 patients: 2 were
      complete responses (CR) (6%) and 11 were partial responses (33.4%). Median
      duration of OR was 7 months (range, 3-27 months). Median duration of CR was 10
      months (range, 4-27 months), and median survival time for patients achieving
      complete response was 30.5 months (range, 28-33 months). Patients with a
      pretreatment creatinine clearance greater than or equal to 50 ml/minute showed a
      higher response rate: 48% OR and 10% CR. Toxicity was evaluated (World Health
      Organization criteria) on 164 cycles and was generally mild. CONCLUSION: CAMV is
      an active and safe regimen in patients with advanced urothelial cancer, even in
      those with impaired renal function. It is recommended that future studies with
      this regimen be performed with pharmacokinetic modulation of carboplatin to
      improve the drug's tolerability and therapeutic activity.

PMID- 8137221
TI  - Low grade supratentorial astrocytomas. Management and prognostic factors.
AB  - BACKGROUND: The authors examined the principal prognostic factors for
      supratentorial low grade astrocytomas and the effects of treatment on survival
      time. METHODS: Fifty-eight patients, 32 males and 26 females, treated from
      January 1970 through December 1990 are reported. Thirty-five patients underwent
      surgery, of whom three died. Among the survivors there were 7 gross total
      resections, 13 subtotal resections, and 12 partial resections. Of the 23
      remaining patients, diagnosis was obtained by stereotactic biopsy. Twenty-five
      patients were irradiated and eight received chemotherapy. The histologic
      material, originally graded 1 or 2 according to Kernohan's system, was reviewed
      using the St. Anne-Mayo Clinic system, with which there were 18 Grade 3 tumors.
      RESULTS: Six patients had pilocytic astrocytomas (mean age, 18 years), of which
      three astrocytomas could be removed, and the patients were well 128, 152, and 254
      months, respectively, after diagnosis. Among the other three patients, one with a
      hypothalamic localization refused any form of treatment and died rapidly. The
      remaining two patients also had deep-seated tumors and were irradiated: one died
      17 months later, and the other remained relapse free 56 months after diagnosis.
      The 49 patients with ordinary astrocytomas who survived surgery (mean age, 37
      years) had a median survival time of 64 months and 5- and 10-year survival rates
      of 54.6% and 34.1%, respectively. Patients with Grade 1 or 2 tumors had a median
      survival time of 108.6 months, compared with 39.4 months for patients with Grade
      3 tumors. Gross total and subtotal resections were significantly associated with
      longer survival time only in patients with Grade 1 and 2 tumors: in this group,
      the 5- and 10-year survival rates were 87.5% and 68.2%, respectively, when tumor
      was completely resected, instead of 57% and 31.2% in patients with incomplete or
      no surgical resection. There was a trend suggesting that antimitotic drugs and X
      ray therapy could benefit patients with Grade 3 tumors. CONCLUSION: The
      importance of an accurate histologic grading system and a gross total resection
      of Grade 1 and 2 astrocytomas is emphasized.

PMID- 8137222
TI  - Prospective investigation of tumor markers and risk assessment in early cancer
      screening.
AB  - BACKGROUND: Many researchers have reported that tumor marker diagnosis may not be
      useful in the early detection of cancer. However, the authors proposed a new
      diagnostic system using a tumor marker combination assay. METHODS: The authors
      screened an asymptomatic population (2126 subjects) in Japan for early cancer
      over a 2-year period (1984-1986) using this tumor marker combination assay. The
      serum tumor marker combination assay data were analyzed: tumor-specific tumor
      markers (carcinoembryonic antigen, carbohydrate 19-9, heat-stable alkaline
      phosphatase, and tissue polypeptide antigen), tumor-associated tumor markers
      (ferritin, the ratio of ferritin to serum iron, immunosuppressive acidic protein,
      sialic acid), and growth-related tumor markers (alkaline phosphatase isoenzymes,
      ribonuclease). The tumor growth levels of the subjects were assessed by the tumor
      marker combination assay and classified into five tumor stages (Stage I,
      tumorfree; Stages II-III, precancer; Stage IV, preclinical cancer; Stage V,
      suggestive of cancer weighing over 1 g). The follow-up period was 5-7 years.
      RESULTS: The percentage of subjects in tumor stages IV and V increased with age,
      whereas the percentage in tumor stages II and III decreased. The distribution of
      screenees within each tumor stage was as follows: I, 0.1%; II, 11.8%; III, 58.8%;
      IV, 24.8%; V, 4.6%. The rate of incidence of cancer for Stages V, VI, III, II and
      I was 29.5% (28 of 95), 2.7% (14 of 528), 0.7% (9 of 1251), 0.4% (1 of 250), and
      0 (0 of 2), respectively. CONCLUSIONS: Our tumor stage classification can
      adequately assess the risk of cancer developing in apparently healthy persons.

PMID- 8137223
TI  - Suramin-induced weakness from hypophosphatemia and mitochondrial myopathy.
      Association of suramin with mitochondrial toxicity in humans.
AB  - BACKGROUND: Suramin is an antiparasitic drug being evaluated as an antitumor
      compound. Suramin therapy commonly causes weakness and is known to cause
      neuropathy. Two potential causes of suramin-induced muscular weakness are
      described. METHODS: Suramin was administered to 15 patients with advanced cancer
      as part of a Phase I study. Weekly dosing was adjusted to achieve mean plasma
      concentrations of 210 micrograms/ml. RESULTS: Serum phosphate levels fell
      significantly (P < 0.0001) in all 15 patients on the 42nd day of treatment from a
      pretreatment average of 4.0 mg/dl (standard deviation [SD] +/- 0.37) to 3.0 mg/dl
      (SD +/- 0.20). Absolute hypophosphatemia developed in two patients with more
      prolonged suramin treatment due to Fanconi's syndrome. The patient who received
      the largest amount of suramin (19.2 g over 14 weeks) had severe proximal muscle
      weakness despite 6 weeks of effective phosphate repletion. A muscle biopsy was
      performed, which demonstrated markedly decreased cytochrome c oxidase activity by
      muscle histochemistry and biochemistry. Electron microscopy revealed
      subsarcolemmal collections of abnormal mitochondria. This mitochondrial myopathy
      resolved clinically 7 weeks after discontinuing suramin. CONCLUSIONS: This report
      indicates that suramin is associated with hypophosphatemia of Fanconi's syndrome
      and a mitochondrial myopathy. The clinical combination of mitochondrial myopathy
      and Fanconi's syndrome is similar to descriptions of congenital mitochondrial
      cytochrome c oxidase deficiency of de Toni-Fanconi-Debre syndrome. These findings
      in humans correlate with the authors' in vitro observations that suramin causes
      toxic mitochondrial changes, indicating a mechanism of suramin's toxicity and
      possibly its antitumor effect.

PMID- 8137224
TI  - Extragonadal germ cell tumors. A 14-year Toronto experience.
AB  - BACKGROUND: Extragonadal germ cell tumors (EGCT) represent only 2-5% of adult
      germ cell malignancies. Because they are rare and biologically distinct from
      testis cancer, their natural history and optimal management continue to be
      defined. The clinical characteristics, treatment, and outcome of 40 patients are
      presented here. METHODS: Patients were identified through the medical records of
      four University of Toronto teaching hospitals. All patients were treated in
      specialized oncology units between 1978 and 1993. RESULTS: Thirty-seven males and
      three females age 16-54 years (median, 24 years) with primary mediastinal (n =
      24), retroperitoneal (n = 7), CNS (n = 7), and widespread (n = 2) EGCT were
      identified. Eight of nine patients (88%) with mediastinal seminoma are alive with
      no evidence of disease (NED) at 4-132 months (median, 45 months). After combined
      modality therapy, only 8 of 15 patients (53%) with mediastinal nonseminomas
      achieved complete remission (CR); 1 experienced relapse and died, resulting in 7
      of 15 patients (47%) with NED at 45-86 months (median, 70 months). All three
      patients with retroperitoneal seminomas achieved CR and all have NED at 77, 103,
      and 120 months, respectively. Two of four patients with retroperitoneal
      nonseminomas have died, and the other two are alive at 36 and 54 months. Seven
      patients with CNS germinomas (seminoma) achieved CR after craniospinal radiation
      therapy, but one subsequently died after local relapse. The overall survival rate
      was 87% (median, 74 months). One patient with widespread choriocarcinoma died and
      the other achieved CR. CONCLUSIONS: Regardless of site of presentation,
      extragonadal seminomas have a greater than 80% 5-year disease-free survival rate.
      Mediastinal nonseminomas are biologically distinct, with a poorer prognosis.
      Treated with cisplatin-based chemotherapy followed by aggressive resection,
      approximately 50% of patients survive. CNS seminomas have a good prognosis.
      Nonseminomas of the CNS are extremely rare and were not represented in the
      current series. These findings concur with other reported series.

PMID- 8137225
TI  - Familial clustering of malignant germ cell tumors and Langerhans' histiocytosis.
AB  - Three sisters in a family with seven children whose grandmother had an ovarian
      embryonal carcinoma experienced development of malignant and a malignant-like
      situation in childhood. Two were diagnosed as having malignant germ cell tumors
      of the ovary, and the third was found to have Langerhans' histiocytosis. The two
      girls with germ cell tumor shared an identical human leukocyte antigen, whereas
      the sister with histiocytosis shared one identical haplotype with them. All three
      children have been treated successfully with chemotherapy and are doing well off
      of treatment.

PMID- 8137226
TI  - Rhabdomyosarcoma of the clitoris.
AB  - Genitourinary rhabdomyosarcoma in females usually originates in the vagina or
      uterus, but rarely the vulva. The authors present a case of rhabdomyosarcoma
      originating in the clitoris. A 4-year-old with an alveolar rhabdomyosarcoma of
      the clitoris was treated with radical clitorectomy, radiation, and chemotherapy.
      Follow-up at 3 years showed no active disease.

PMID- 8137227
TI  - Pediatric malignant glioma with tubuloreticular inclusions and MYCN
      amplification. Report of a case with immunohistochemical, ultrastructural, flow
      cytometric, karyotypic, and Southern blot analysis.
AB  - BACKGROUND: The authors described unusual pathologic features in a left frontal
      lobe malignant glioma in a 31/2-year-old boy. The pathology was similar in the
      initial excision and two subsequent recurrences at 9 and 11 months and at
      autopsy, when extensive subarachnoid spread was noted. METHODS: The tumor was
      studied by conventional histology, immunohistochemistry, flow cytometry,
      transmission electron microscopy (TEM), immune electron microscopy (IEM), and
      cytogenetic and Southern blot analysis. RESULTS: The tumor revealed two different
      histologic patterns. One component showed large cells with eosinophilic
      cytoplasm, vesicular nuclei with prominent nucleoli, eosinophilic perinuclear
      inclusions, and immunoreactivity for glial fibrillary acidic protein (GFAP) and
      vimentin. The other component consisted of undifferentiated cells with
      hyperchromatic nuclei and scanty cytoplasm. By TEM, the perinuclear aggregates
      were composed of tubuloreticular inclusions, which were also observed in
      endothelial cells within the tumor vasculature. By IEM, the intermediate
      filaments in the tumor cell cytoplasm were decorated with GFAP. Flow cytometric
      results revealed a marked increase in the S-phase (48%), whereas cytogenetic
      analysis of short-term cultures showed an abnormal karyotype containing marker
      chromosomes and double minutes. In the second resection, additional karyotypic
      abnormalities were noted, including 1p- and several additional markers. The first
      and second resections showed MYCN amplification by Southern Blot analysis in the
      60- to 80-fold range. CONCLUSIONS: This tumor presents unique histologic,
      ultrastructural, and cytogenetic findings as well as MYCN amplification that is
      notable for a pediatric malignant glioma. Tubuloreticular inclusions were a
      prominent feature in this tumor, which again is unique for a glioma.

PMID- 8137228
TI  - The National Cancer Data Base report on breast cancer.
AB  - BACKGROUND: Previous National Cancer Data Base data have been used to examine
      time trends in stage of disease and treatment patterns for breast cancer. The
      most current (1990) data are described here. METHODS: Two calls for data have
      yielded a total of 143,051 breast cancer cases for 1985, 1988, and 1990 from
      hospital cancer registries across the United States. RESULTS: The percentage of
      in situ cancers increased between 1985 and 1988 but was essentially constant
      between 1988 and 1990. The use of breast-conserving partial mastectomy across the
      country increased between 1988 and 1990. Some interesting regional differences
      appeared in the use of multimodality treatment. CONCLUSIONS: These data suggest a
      plateau in the use of mammographic screening.

PMID- 8137229
TI  - The syndrome of 5-fluorouracil cardiotoxicity: an elusive cardiopathy.

PMID- 8137230
TI  - Hepatitis C virus antibody in patients with primary liver cancer (hepatocellular
      carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma) in
      Japan.

PMID- 8137231
TI  - Mammography screening for breast cancer.

PMID- 8137232
TI  - Recent results of management of palpable clinically localized prostate cancer.

PMID- 8137233
TI  - Squamous carcinoma presenting as an enlarged cervical lymph node.

PMID- 8137234
TI  - An immunohistochemical study of ras oncoprotein expression in gastric carcinoma.

PMID- 8137235
TI  - A candidate tumor suppressor gene in human breast cancers.
AB  - We have isolated a candidate gene (designated Brush-1) located at 13q12-q13,
      proximal to the retinoblastoma gene (RB1). Brush-1 codes for a 4.7-kilobase mRNA
      expressed at high levels in normal breast epithelium but drastically reduced in 6
      of 13 breast cancer cell lines. RB1 mRNA expression is at normal levels for 5 of
      these 6 lines suggesting a greater importance of Brush-1 for breast cancer. Four
      primary breast tumors which showed no loss of heterozygosity in the 13q13-q14
      region demonstrated normal levels of mRNA for both Brush-1 and RB1. However, four
      additional primary tumors which displayed loss of heterozygosity for this region
      had markedly decreased levels of Brush-1 mRNA while maintaining the normal levels
      for RB1. This differential loss of Brush-1 mRNA expression for both primary
      tumors and breast cancer cell lines is the expected pattern for a breast tumor
      suppressor gene.

PMID- 8137236
TI  - Loci associated with malignant progression in astrocytomas: a candidate on
      chromosome 19q.
AB  - WHO grades II and III astrocytomas frequently exhibit loss of genetic material on
      chromosomes 9p, 11p, 17p, 19q, and 22q, indicating that these chromosomal regions
      harbor tumor suppressor genes involved in the pathogenesis of astrocytic
      neoplasms. The present study was conducted to examine whether these genetic
      regions are involved in the process of malignant progression from astrocytoma WHO
      grade II (A II) to anaplastic astrocytoma WHO grade III (A III). We have analyzed
      44 astrocytomas, i.e., 18 A II and 26 A III for loss of heterozygosity (LOH) on
      chromosomes 1p, 1q, 9p, 9q, 10p, 10q, 11p, 13q, 17p, 19p, 19q, and 22q and for
      amplification of the epidermal growth factor receptor gene. A polymerase chain
      reaction-based assay with microsatellite repeat sequences was used for the
      detection of polymorphisms on silver-stained polyacrylamide gels. LOH on 9p was
      seen in 1 of 18 (6%) informative cases of A II and 4 of 24 (17%) informative
      cases of A III. LOH on 17p was observed in 9 of 17 (53%) informative cases of A
      II and 15 of 26 (58%) informative cases of A III. LOH on 19q was detected in 2 of
      18 (11%) informative cases of A II and in 12 of 26 (46%) informative cases of A
      III. The association of LOH on 19q with anaplasia in astrocytoma was significant
      (P = 0.015). Amplification of the epidermal growth factor receptor gene was not
      detected in A II or A III. These data suggest that a putative tumor suppressor
      gene on the long arm of chromosome 19 is a candidate for a gene associated with
      tumor progression in astrocytic gliomas.

PMID- 8137237
TI  - Correlation between E2F-1 requirement in the S phase and E2F-1 transactivation of
      cell cycle-related genes in human cells.
AB  - The mammalian nuclear protein E2F-1 has recently been cloned based on its ability
      to bind the retinoblastoma protein. To determine whether E2F-1 plays a role in
      the control of the cell proliferation, we introduced an inducible construct
      expressing an E2F-1 antisense RNA into the human glioblastoma T98G cell line and
      assessed DNA synthesis during the cell cycle. Expression of the antisense
      transcripts during the G1-S transition resulted in a marked delay in the
      completion of DNA synthesis. Band-shift analysis of bacterially produced E2F-1
      showed that this protein bound to the promoters of human DNA polymerase-alpha,
      cyclin D1, and c-myb but not to the cdc2 gene promoter. E2F-1 also transactivated
      the bound promoters in transient transfection assays. These results suggest a
      major role for E2F-1 in the control of cell cycle progression via transcriptional
      regulation of proliferation-associated genes.

PMID- 8137238
TI  - Epidermal growth factor modifies cell cycle control in A431 human squamous
      carcinoma cells damaged by ionizing radiation.
AB  - Epidermal growth factor (EGF) has been shown to radiosensitize A431 and other
      human squamous carcinoma cells with high numbers of surface EGF receptors. In
      this study of the mechanistic basis of EGF-induced radiosensitization, both EGF
      and ionizing radiation caused G1 phase arrests in cycling A431 cells, but only
      radiation caused a G2-M arrest. However, EGF enhanced the magnitude of this G2-M
      arrest, suggesting an interaction of signaling pathways involved in cellular
      responses to EGF and radiation damage. EGF and radiation also uniquely perturbed
      cyclin A and B1 mRNA levels during the time of maximum radiation-induced G2-M
      arrest. The effects of EGF on G2-M events probably originated in cells in G1. It
      is possible that aberrant EGF signal transduction in human squamous carcinoma
      cells may be exploited as a novel strategy for radiotherapy.

PMID- 8137239
TI  - Ionizing radiation induces rapid tyrosine phosphorylation of p34cdc2.
AB  - Eukaryotic cells respond to ionizing radiation exposure with cell cycle arrest.
      However, little is known about the signaling mechanisms responsible for this
      effect. The present work has asked whether ionizing radiation exposure is
      associated with changes in phosphorylation of proteins in HL-60 myeloid leukemia
      cells. The results demonstrate increased tyrosine phosphorylation of a M(r)
      34,000 substrate. This effect was detectable at 1 to 10 min after irradiation and
      was induced by doses of 50 to 500 cGy. Immunoprecipitation studies further
      suggest that this substrate is the serine/threonine p34cdc2 protein kinase. Since
      p34cdc2 is required for entry into mitosis, these findings support the
      posttranslational modification of a cell cycle regulatory protein in the response
      to ionizing radiation.

PMID- 8137240
TI  - Estramustine sensitizes human glioblastoma cells to irradiation.
AB  - Estramustine is an estradiol-based antimicrotubule agent that accumulates in
      malignant glioma cells, resulting in a concentration-dependent inhibition of
      proliferation. This agent has been shown to synchronize human glioma cells at G2
      M consistent with its known effects on the mitotic spindle and potentially could
      be used as a radiation enhancer. We determined the effects of estramustine on the
      cell cycle of glioblastoma cells by flow cytometry. These findings were compared
      with clonogenic survival in cells pretreated with varying concentrations of
      estramustine prior to irradiation. These experiments indicated that 24 h
      treatment with 1 microM estramustine had no effect on the percentage of G2-M
      cells and did not enhance the cytotoxic effects of radiation while 10 microM
      estramustine increased the G2-M fraction by 100% associated with a potentiation
      factor as high as 8.5 and a relative radiation sensitivity at 70% cytotoxicity of
      5.2 compared with 15.4 for control cells. Estramustine can be administered p.o.
      on a daily schedule with minimal systemic toxicity. These data suggest that
      estramustine may be an effective radiation enhancer for glioblastoma.

PMID- 8137241
TI  - Constitutive DNA binding of the low mobility forms of the AP-1 and SP-1
      transcription factors in HL60 cells resistant to 1-beta-D
      arabinofuranosylcytosine.
AB  - DNA binding of the AP-1 transcription factor, a dimer of jun-fos or jun-jun
      proteins, is regulated during monocytic differentiation of HL60 cells. The
      abundance of AP-1 complexes capable of binding to DNA increases and complexes
      with slow electrophoretic mobility appear after exposure of HL60 cells to 1,25
      dihydroxyvitamin D3. Similar changes are seen in the SP-1 transcription factor.
      In contrast, variants of HL60 cells that are resistant to both 1,25
      dihydroxyvitamin D3 and 1-beta-D-arabinofuranosylcytosine constitutively express
      the slowly migrating AP-1 and SP-1 complexes which are found only in the
      differentiated parental HL60 cells. Because this form of AP-1 complex is highly
      phosphorylated, the data show that altered phosphorylation of at least two
      transcription factors is associated with resistance to 1-beta-D
      arabinofuranosylcytosine.

PMID- 8137242
TI  - Homozygous deletions of 9p21 in primary human bladder tumors detected by
      comparative multiplex polymerase chain reaction.
AB  - Deletion mapping studies of primary bladder tumors have identified nonoverlapping
      areas of loss on each arm of chromosome 9, indicating that two distinct tumor
      suppressor loci are located on this chromosome. The deleted region on the p arm
      overlaps an area of 9p previously reported to be lost in a variety of neoplasms.
      Detailed loss of heterozygosity analysis of 9p in 112 primary bladder tumors
      using 12 microsatellite markers identified a minimal area of loss around the
      alpha-interferon locus at 9p21-22. Frequent homozygous deletions of the alpha
      interferon locus were then identified in these tumors by a novel, comparative,
      multiplex polymerase chain reaction assay and were subsequently confirmed by
      Southern analysis. Based on these deletions, a putative tumor suppressor gene
      locus involved in bladder tumorigenesis was localized to a 10 cM region (flanked
      by D9S162 and D9S171), previously implicated in the progression of many
      neoplasms. Application of the multiplex polymerase chain reaction-based assay
      will allow rapid identification of homozygous deletions in many neoplasms and
      thus aid in mapping studies of critical suppressor genes.

PMID- 8137243
TI  - Hypoxia causes the activation of nuclear factor kappa B through the
      phosphorylation of I kappa B alpha on tyrosine residues.
AB  - The response of mammalian cells to stress is controlled by transcriptional
      regulatory proteins such as nuclear factor kappa B (NF-kappa B) to induce a wide
      variety of early response genes. In this report, we show that exposure of cells
      to hypoxia (0.02% O2) results in I kappa B alpha degradation, increased NF-kappa
      B DNA binding activity, and transactivation of a reporter gene construct
      containing two NF-kappa B DNA binding sites. Pretreatment of cells with protein
      tyrosine kinase inhibitors and the dominant negative allele of c-Raf-1 (Raf 301)
      inhibited I kappa B alpha degradation, NF-kappa B binding, and transactivation of
      kappa B reporter constructs by hypoxia. To demonstrate a direct link between
      changes in the phosphorylation pattern of I kappa B alpha with NF-kappa B
      activation, we immunoprecipitated I kappa B alpha after varying times of hypoxic
      exposure and found that its tyrosine phosphorylation status increased during
      hypoxic exposure. Inhibition of the transfer of tyrosine phosphoryl groups onto I
      kappa B alpha prevented I kappa B alpha degradation and NF-kappa B binding. In
      comparison to other activators of NF-kappa B such as phorbol myristate acetate or
      tumor necrosis factor, we did not detect changes in the tyrosine phosphorylation
      status of I kappa B alpha following treatment with either of these agents. These
      results suggest that tyrosine phosphorylation of I kappa B alpha during hypoxia
      is an important proximal step which precedes its dissociation and degradation
      from NF-kappa B.

PMID- 8137244
TI  - Camptothecins: from bench research to hospital wards.

PMID- 8137245
TI  - Histogenesis of induced prostate and seminal vesicle carcinoma in Lobund-Wistar
      rats: a system for histological scoring and grading.
AB  - We have developed a grading system for the evaluation of the histogenesis of
      neoplastic lesions of the prostate and seminal vesicle of the laboratory rat.
      Prostatic and seminal vesicle carcinomas were induced in Lobund-Wistar rats by
      initiation with 30 mg/kg N-nitroso-N-methylurea i.v., followed by promotion with
      40 mg testosterone propionate implants 1 week later and at 3-month intervals
      thereafter. Experimental and control groups were sacrificed at various time
      points between 5 and 11 months after dosing with N-nitroso-N-methylurea in order
      to visualize progressive stages of carcinogenesis of the dorsolateral prostate,
      the anterior prostate, and the seminal vesicle. A system of staging was created
      which allows three different categories (in situ change, invasion, desmoplasia)
      of tumor development to be ranked progressively in a manner conducive to
      nonparametric analysis. Each category was then further subdivided to create a
      total of six stages. This system can be used to evaluate agents which modify
      tumor induction or suppression. The application of this staging system to the
      measurement of the effects of the synthetic retinoid, 4-hydroxyphenyl retinamide,
      on prostatic carcinogenesis in the Lobund-Wistar rat is described.

PMID- 8137246
TI  - Chemoprevention of spontaneous endometrial cancer in female Donryu rats by
      dietary indole-3-carbinol.
AB  - Indole-3-carbinol (I3C) present in cruciferous vegetables has been found to
      inhibit chemically induced neoplasms in forestomach, mammary gland, liver, and
      tongue in rodents. I3C is also known to induce estradiol 2-hydroxylase and reduce
      estrogenic activity. The current study was conducted to examine the possible
      inhibiting effect of I3C on spontaneous occurrence of endometrial adenocarcinoma
      in female Donryu rats. The high incidence of endometrial cancer in this strain of
      rats might be related to increased estrogen/progesterone ratio with aging. A
      total of 141 female Donryu rats were divided into four groups. Group 1 was given
      a basal diet alone throughout the study. Starting at 6 weeks of age, groups 2-4
      were respectively given the diets containing 200, 500, and 1000 ppm I3C for the
      entire experimental period (660 days). At the termination of the experiment, the
      incidences of preneoplastic lesions and neoplasms in the endometrium were
      estimated. Also, estradiol 2-hydroxylation activity in the liver was assayed in
      rats fed I3C at these doses for 3 weeks. The incidences of endometrial
      adenocarcinoma in rats fed I3C [8 of 32 rats (25%) in group 2, 5 of 32 rats (16%)
      in group 3, and 5 of 35 rats (14%) in group 4] were respectively smaller than
      that in group 1 (12 of 32 rats, 38%). The incidence of uterine adenocarcinoma in
      group 4 was significantly lower than that in group 1 (P < 0.05). Dietary I3C also
      decreased the frequency of preneoplastic endometrial lesions (31% in groups 2-4
      versus 44% in group 1). I3C exposure also inhibited the incidence of mammary
      fibroadenoma. Biochemical assay for estradiol 2-hydroxylation revealed that
      feeding of I3C significantly increased estradiol 2-hydroxylation (nmol/mg
      protein) compared to rats treated without I3C [0.34 +/- 0.04 in group 2, 0.53 +/-
      0.13 in group 3, and 0.58 +/- 0.11 in group 4 versus 0.28 +/- 0.02 in group 1; P
      < 0.02, P < 0.003, and P < 0.001, respectively]. These results suggest that
      dietary I3C inhibits spontaneous occurrence of endometrial adenocarcinoma as well
      as preneoplastic lesions in Donryu rats. This chemopreventive effect of I3C may
      be due to its induction of estradiol 2-hydroxylation.

PMID- 8137247
TI  - A phase I study of swainsonine in patients with advanced malignancies.
AB  - Swainsonine, an alpha-mannosidase inhibitor which blocks Golgi oligosaccharide
      processing, represents a new class of compounds that inhibit both rate of tumor
      growth, and metastasis, in murine experimental tumor models. In this first phase
      I study, the quantitative and qualitative toxicities of swainsonine have been
      studied in patients given a continuous i.v. infusion over 5 days, repeated at 28
      day intervals. Dose levels were escalated in increments of 100 micrograms/kg/day
      from 50-550 micrograms/kg/day. Nineteen patients with both solid tumor and
      hematological malignancies were given a total of 31 courses. Hepatotoxicity,
      particularly in patients with liver metastases, was the dose-limiting toxicity.
      The maximum tolerated dose (MTD) and the recommended starting dose (MTD -1 level)
      were 550 and 450 micrograms/kg/day, respectively. Common side effects included
      edema, mild liver dysfunction, a rise in serum amylase, and decreased serum
      retinol. Acute respiratory distress syndrome possibly precipitated by swainsonine
      resulted in a treatment-related death in a patient with significant pretreatment
      hepatic dysfunction. One patient with head and neck cancer showed > 50% shrinkage
      of tumor mass for 6 weeks after treatment. Two patients with lymphangitis
      carcinomatosis on chest X-ray noted improvement in cough and shortness of breath
      during the infusion of swainsonine and for 1 week thereafter. Clearance and serum
      half-life for swainsonine were determined to be approximately 2 ml/h/kg, and 0.5
      day, respectively. Golgi oligosaccharide processing, a putative anticancer target
      for swainsonine was inhibited in peripheral blood lymphocytes as evidenced by a
      marked decrease in leukoagglutinin binding after 5 days of treatment.
      Oligomannosides in patient urine increased 5-to 10-fold over the 5 days of
      treatment, indicating that tissue lysosomal alpha-mannosidases were also blocked
      by swainsonine. Urine oligomannoside accumulation reached steady state at 3 days,
      approximately 1 day after serum drug levels reached steady state. The fraction of
      HLA-DR-positive cells in peripheral blood lymphocytes increased following 5 days
      of swainsonine treatment, an effect similar to that observed for peripheral blood
      lymphocytes from normal subjects cultured with swainsonine. No significant
      changes in CD3, CD4, CD8, CD16, and CD25 were observed. Swainsonine produces
      minimal toxicity when administered i.v. to cancer patients at dosages that
      inhibit both Golgi alpha-mannosidase II and lysosomal alpha-mannosidases.
      Detection of hepatic metastases or liver enzyme abnormalities prior to treatment
      predict for more significant toxicity.

PMID- 8137248
TI  - Antiestrogenic effects of all-trans-retinoic acid and 1,25-dihydroxyvitamin D3 in
      breast cancer cells occur at the estrogen response element level but through
      different molecular mechanisms.
AB  - Most breast tumors show estrogen-dependent growth and are thus susceptible to
      antiestrogenic therapy. MCF-7 cells, obtained from a human estrogen-dependent
      breast carcinoma, are widely used for studying the modulation of estrogenic
      responses by different effectors. All-trans-retinoic acid (RA) and 1,25
      dihydroxyvitamin D3 (Vit D3) inhibited estrogen-induced growth of MCF-7 cells and
      their effect was potentiated by the classical antiestrogen, hydroxytamoxifen. In
      MCF-7 cells, we found that RA and Vit D3 also inhibited estrogen-induced
      transcription; this was shown both for an endogenous gene (pS2) and for various
      exogenous transfected genes. Their inhibitory effect could not be reversed by
      increasing estradiol concentrations, showing that contrary to classical
      antiestrogens, they did not compete with estradiol to bind the estrogen receptor
      (ER). Analysis of the inhibitory mechanisms indicates that RA and Vit D3
      receptors can directly or indirectly impair the binding of ER to the estrogen
      responsive element. The antagonist effect of RA would be found especially at DNA
      level since it seems to essentially involve an estrogen responsive element. The
      antagonist effect of Vit D3 would be found especially at the ER level since it
      seems to concern estrogen binding and dimerization domains of ER. We conclude
      that the antiestrogenic effects of RA and Vit D3 are similar since they can, via
      their receptors, interfere with estrogenic action at the estrogen responsive
      element level but that they are not identical since different molecular
      mechanisms are involved.

PMID- 8137249
TI  - AA1, a newly synthesized monovalent lipophilic cation, expresses potent in vivo
      antitumor activity.
AB  - Certain lipophilic cations have been reported to display anticarcinoma activities
      because of their selective uptake and retention by mitochondria of cancer cells.
      Thus, these agents may comprise a unique class of agents directed against
      carcinoma. After screening more than 1000 lipophilic cations, we found that the
      monovalent lipophilic cation, 2,6-bis(4-amino-phenyl)-4-[4
      (dimethylamino)phenyl]thiopyrylium chloride (AA1), displayed remarkable
      anticarcinoma activity both in vitro and in vivo. Unlike most other lipophilic
      cations, AA1 is stable and displays minimal light sensitivity. In vitro testing
      showed that AA1 was 10 times more toxic to the carcinoma cell line CX-1 than to
      the normal epithelial cell line CV-1. In vivo animal experiments showed that AA1
      significantly prolonged the survival of mice implanted with tumors. For C57BL x
      DBA/2 F1 mice implanted with the mouse bladder carcinoma cell line, MB49, the
      treated:control ratio was 344%. For Swiss nu/nu mice implanted i.p. with the
      human melanoma cell line, LOX, the treated:control ratio was 341%. The most
      significant observation was obtained with Swiss nu/nu mice that were implanted
      i.p. with the human ovarian cell line, OVCAR-III. The treated:control ratio in
      this situation was greater than 450%. In all these tumor models, AA1 produced
      minimal toxicities. AA1 exhibited little inhibition of electron transport in
      isolated rat liver mitochondria; however, it inhibited mitochondrial ATPase with
      50% inhibitory concentration of 6 microM. Compared with previously reported
      anticarcinoma lipophilic cations such as rhodamine 123 and dequalinium chloride,
      AA1 appeared to display more effective in vivo anticarcinoma activity. Thus, AA1
      could be considered for further clinical development as a candidate for
      anticarcinoma chemotherapy.

PMID- 8137250
TI  - Potentiation of the antitumor activity of 5-fluorouracil in colon carcinoma cells
      by the combination of interferon and deoxyribonucleosides results from
      complementary effects on thymidine phosphorylase.
AB  - alpha-Interferon (IFN alpha) potentiates the cytotoxicity of 5-fluorouracil
      (FUra) in vitro, and the combination has clinical efficacy in advanced colorectal
      cancer. We have reported previously an IFN alpha-mediated elevation in cellular
      FdUMP levels accompanied by the stimulation of thymidine phosphorylase (TP)
      activity in extracts from HT-29 human colon carcinoma cells treated with IFN
      alpha. We have now found that this effect of IFN alpha can be measured in vivo as
      an increase in thymine incorporation in intact cells. The increase was only 3
      fold, however, compared to the 12-fold increase seen in TP activity in cell
      extracts. This suggested that the cosubstrate for TP, deoxyribose-1-phosphate,
      was rate limiting in the cells. Since the synthetic pathway of TP can also
      proceed via a transferase reaction, natural and modified deoxyribonucleosides
      were tested as deoxyribosyl donors. TP activity was measurable in cell extracts
      using deoxyinosine as cosubstrate with either thymine or FUra, although activity
      was only 10% of that measured with deoxyribose-1-phosphate. The pyrimidine
      analogue 5-propynyloxy-2'-deoxyuridine (PO-dUrd) had 15% of the maximal TP
      activity in cell extracts and also increased thymine incorporation in intact
      cells 10-fold. Both 2'-deoxyinosine and PO-dUrd potentiated the cytotoxicity of
      FUra by 8-11-fold. IFN alpha potentiated the cytotoxicity of FUra by 1.8-fold,
      and the combination of IFN alpha and PO-dUrd produced a 25-fold increase in the
      cytotoxicity of FUra. Neither the corresponding analogue riboside, 5
      propynyloxyuridine, nor the analogue base, 5-propynyloxyuracil, had any effect on
      FUra cytotoxicity. There was a significant correlation between the ability of a
      nucleoside and/or IFN alpha combination to increase thymine incorporation and to
      reduce the 50% inhibitory concentration for FUra. IFN alpha and PO-dUrd also
      potentiated the inhibition by FUra of thymidylate synthase activity. These
      findings suggest that the use of a deoxyribonucleoside to provide the rate
      limiting cosubstrate would complement the stimulation of TP by IFN alpha, and
      together they should further enhance the antitumor activity of FUra.

PMID- 8137251
TI  - Antitumor activity of free and liposome-entrapped annamycin, a lipophilic
      anthracycline antibiotic with non-cross-resistance properties.
AB  - The lipophilic anthracycline antibiotic annamycin (Ann) was entrapped in
      liposomes of different size [median diameter: 1.64 microns, multilamellar
      liposomal Ann (L-Ann); 0.030 micron, small unilamellar Ann (S-Ann)] with > 90%
      entrapment efficiency and tested in vitro against four pairs of sensitive and
      multidrug-resistant (MDR) tumor cell lines and in vivo by the i.v. route in five
      tumor models: advanced s.c. B16 melanoma; s.c. M5076 reticulosarcoma; lung
      metastases of Lewis lung carcinoma; and s.c. KB and KB-V1 xenografts in nude
      mice. Predetermined optimal doses of the different formulations were used and the
      results were compared with doxorubicin (Dox). In vitro, Ann, either in suspension
      in 10% dimethyl sulfoxide (F-Ann) (1 mg/ml) or entrapped in liposomes, was able
      to partially overcome resistance in all four pairs of sensitive and MDR KB, 8226,
      P388, and CEM cell lines (resistance indexes 63, 269, 333, and 356 for Dox versus
      4, 5, 19, and 8.7 for L-Ann, respectively). In vivo, both F-Ann and liposome
      entrapped Ann were slightly more effective than Dox in inhibiting the growth of
      advanced s.c. B16 melanoma tumors. L-Ann was markedly more effective than Dox and
      moderately more effective than F-Ann in prolonging the life span of animals
      bearing s.c. M5076 and lung metastases of Lewis lung carcinoma tumors. All drugs
      were equally effective at optimal doses in delaying the growth of s.c. KB
      xenografts, whereas all Ann formulations were markedly more effective than Dox in
      delaying the growth of s.c. KB-V1 (MDR) xenografts. In all in vivo experiments, S
      Ann was consistently more effective than L-Ann and L-Ann was more effective than
      F-Ann. These results indicate that (a) Ann is more effective than Dox by the i.v.
      route against several tumor models and that MDR tumors are partially not cross
      resistant to Ann both in vitro and in vivo, (b) liposomes enhance the in vivo
      antitumor properties of Ann, and (c) small liposomes are more effective than
      large liposomes in enhancing Ann antitumor activity.

PMID- 8137252
TI  - Regression of human breast tumor xenografts in response to (E)-2'-deoxy-2'
      (fluoromethylene)cytidine, an inhibitor of ribonucleoside diphosphate reductase.
AB  - (E)-2'-Deoxy-2'-(fluoromethylene)cytidine (MDL 101,731) is a mechanism-based
      inhibitor of ribonucleoside diphosphate reductase (J. Stubbe, personal
      communication), an enzyme involved in DNA synthesis and therefore a potential
      target for cancer chemotherapy. In the present report, we show that MDL 101,731
      inhibits the proliferation of several human breast cancer cell lines, including
      the estrogen-dependent cell line, MCF-7, and the estrogen-independent cell lines
      MDA-MB-231, MDA-MB-468, and MDA-MB-435 in vitro at nanomolar concentrations (50%
      inhibitory concentration, 15-26 nM). Administration of MDL 101,731 caused marked
      regression of tumors which formed after s.c. inoculation of all four of the cell
      lines in athymic (nude) mice. MDA-MB-231 tumors were found to be most sensitive
      to MDL 101,731 with a 90-100% cure rate at doses of MDL 101,731 between 2 and 20
      mg/kg, given as once daily i.p. injections, 5 days/week for as little as 3 weeks.
      Almost complete cessation of MDA-MB-231 tumor growth was obtained with a dose of
      0.5 mg/kg MDL 101,731 following the same dosing regimen. MDA-MB-468, MDA-MB-435,
      and MCF-7 tumors were not as sensitive as MDA-MB-231, but tumor regression of 50,
      65, and 80%, respectively, was obtained after 5-6 weeks of treatment. The effects
      of MDL 101,731 on spontaneous metastasis of MDA-MB-435 cells from the mammary fat
      pad to the lung was also examined, and it was found that the number of lung
      metastases was significantly decreased if mice received MDL 101,731 while the
      primary tumors were growing and after primary tumors were surgically excised.
      Additionally, preliminary evidence raises the possibility that MDL 101,731 may
      induce apoptosis in MDA-MB-231 tumors. Our data suggest that the use of MDL
      101,731 for the treatment of breast cancer and possibly other solid tumors should
      be pursued.

PMID- 8137253
TI  - Altered cytotoxicity of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea in human
      glioma cell lines SK-MG-1 and SKI-1 correlates with differential transport
      kinetics.
AB  - Resistance to (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU), an
      experimental anticancer compound, was investigated in the chloroethylnitrosourea
      sensitive Mer- SK-MG-1 and -resistant Mer- SKI-1 human glioma cell lines. The
      transport of [3H]SarCNU was examined in suspension. The uptake of [3H]SarCNU was
      found to be temperature dependent in SK-MG-1 and SKI-1, but less so in SKI-1. At
      37 degrees C, uptake of 50 microM [3H]SarCNU was linear up to 4 s in both cell
      lines, with uptake being significantly faster in SK-MG-1 than in SKI-1 under
      initial rate conditions. There was no significant difference in the rate of
      influx at 22 degrees C between both cell lines. Equilibrium was approached after
      1 min at 22 and 37 degrees C. At 37 degrees C, steady state accumulation of
      SarCNU at 30 min was reduced significantly (35%) in SKI-1 cells compared with SK
      MG-1 cells, although accumulation was similar at 22 degrees C. In SK-MG-1 cells,
      uptake of [3H]SarCNU at 37 degrees C was found to be saturable, but uptake in SKI
      1 cells was not saturable over a 1000-fold range of concentrations. Analysis of
      efflux in cells preloaded with 50 microM [3H]SarCNU revealed that the rate of
      efflux was equivalent in both cell lines but that the efflux rate was more rapid
      at 37 degrees C compared with 22 degrees C. Metabolism of SarCNU at 37 degrees C
      was not different in either cell line after a 60-min incubation, as determined by
      thin layer chromatography. SKI-1 cells, compared with SK-MG-1 cells, were 3-fold
      more resistant to SarCNU at 37 degrees C but only 2-fold more resistant at 22
      degrees C, a temperature at which SarCNU accumulation was similar in both cell
      lines. The 2-fold resistance at 22 degrees C was similar to that of 1,3-bis(2
      chloroethyl)-1-nitrosourea at 37 and 22 degrees C. These findings indicate that
      increased cytotoxicity in SK-MG-1 cells is associated with a greater accumulation
      of SarCNU via an epinephrine-sensitive carrier that is not detectable in SKI-1
      cells. However, part of the chloroethylnitrosourea resistance in SKI-1 cells is
      not secondary to decreased accumulation.

PMID- 8137255
TI  - Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo
      with 5-fluorocytosine and induce protective immunity to wild type tumor.
AB  - Successful expression of the cytosine deaminase (CD) suicide gene in vivo is
      demonstrated in three weakly immunogenic murine tumor models: the 102 and 205
      fibrosarcomas and the 38 adenocarcinoma. Normal mammalian cells do not contain
      cytosine deaminase, but tumor cells transduced with retroviral vectors containing
      the CD gene metabolize the relatively nontoxic prodrug 5-fluorocytosine to the
      highly toxic 5-fluorouracil. In vitro cells expressing the CD gene are killed by
      5-fluorocytosine while unmodified cells are not. When injected into syngeneic
      mice, CD+ tumors can also be eliminated in vivo by systemic treatment with 5
      fluorocytosine without significant toxicity to the host. Animals whose CD+ tumors
      were eliminated with prodrug treatment resist subsequent rechallenge with
      unmodified wild type tumor. This posttreatment immunity appears to be tumor
      specific. Applications of the CD system in gene therapy models are discussed.

PMID- 8137254
TI  - cis-Diamminedichloroplatinum(II) resistant human tumor cell lines are
      collaterally sensitive to PtCl4(Rh-123)2: evidence for mitochondrial involvement.
AB  - Three human tumor cell lines made resistant to cis-diamminedichloroplatinum(II)
      (CDDP), SCC-25/CP, MCF-7/CP, and C13, are more sensitive to rhodamine-123
      [tetrachloroplatinum(II)] [(PtCl4(Rh-123)2] than are the corresponding parental
      cell lines. The CDDP-resistant cells have higher intracellular concentrations of
      PtCl4(Rh-123)2 for the same exposure than do the parent cells. Each of the CDDP
      resistant cell lines has an increased level of cytochrome c oxidase activity
      compared with the parent cell lines, indicating that the resistant cells have
      greater mitochondrial mass or activity than the parent cells. In fact, there was
      a linear correlation between the increase in cytochrome c oxidase activity and
      the increased sensitivity to PtCl4(Rh-123)2 in the CDDP-resistant lines. Exposure
      of the cells to each of the mitochondrial effectors, chloramphenicol, FCCP,
      oligomycin, or antimycin prior to and during exposure to CDDP or PtCl4(Rh-123)2
      had variable effects on the cytotoxicity of the platinum complexes in the
      parental lines. However, there was a consistent decrease in the cytotoxicity of
      PtCl4(Rh-123)2 in the CDDP-resistant cells in the presence of the mitochondrial
      effectors such that, in some cases, the CDDP-resistant lines were now less
      responsive to PtCl4(Rh-123)2 than were the parent cell lines. These studies
      indicate that mitochondrial alterations may be an important component of CDDP
      resistance in these cell lines and that PtCl4(Rh-123)2 may represent a prototype
      platinum complex useful in the treatment of CDDP resistant tumors.

PMID- 8137256
TI  - 5-Ethynyluracil (776C85): modulation of 5-fluorouracil efficacy and therapeutic
      index in rats bearing advanced colorectal carcinoma.
AB  - 5-Ethynyluracil (EU; 776C85) is a potent inactivator of dihydropyrimidine
      dehydrogenase, the enzyme that rapidly degrades 5-fluorouracil (FUra). We have
      investigated the antitumor activity and toxicity of FUra alone and in combination
      with EU in rats bearing advanced colon carcinoma. Two schedules were studied: (a)
      FUra daily for 4 days i.v. push (daily x 4); and (b) FUra administered i.v. push
      weekly for 3 weeks (weekly x 3). EU was administered at 1 mg/kg 1 h before FUra
      and for two additional days post-FUra therapy. The maximum tolerated doses of
      FUra alone were 35 and 100 mg/kg/day and for FUra plus EU were 10 and 15
      mg/kg/day for the daily x 4 and weekly x 3 schedules, respectively. The dose
      limiting toxicities were diarrhea and stomatitis both for FUra alone and for FUra
      in combination with EU. Although EU was not toxic and not active as an antitumor
      agent, it markedly improved the efficacy and therapeutic index of FUra. The
      antitumor activity of FUra was schedule dependent, yielding 13% complete and
      sustained tumor regression on the weekly schedule and no complete and sustained
      tumor regression on the daily schedule. The combination of FUra and EU produced
      100% complete and sustained tumor regression on both schedules. The therapeutic
      index was < or = 1 for FUra alone and 6 for FUra with EU. EU was considerably
      more effective than either leucovorin or N-(phosphonacetyl)-L-aspartate as a
      modulator of FUra. Leucovorin or N-(phosphonacetyl)-L-aspartate induced minimum
      improvements on the daily schedule and only increased the therapeutic index to
      1.5 on the weekly schedule. Because a 4-day continuous infusion of FUra alone at
      the maximum tolerated dose did not improve FUra therapy, we conclude that the
      improvements by EU involve additional modulations that complement the enhanced
      exposure of FUra.

PMID- 8137257
TI  - Chimeric anti-ganglioside GM2 antibody with antitumor activity.
AB  - Ganglioside GM2, which is one of the major gangliosides expressed on the cell
      surface of human tumors of neuroectodermal origin, has been focused on as a
      target molecule for passive immunotherapy. GM2 is thought to be one of the T-cell
      independent antigens and to elicit only IgM antibody responses in rodents and
      humans. We have previously established two murine anti-GM2 monoclonal antibodies
      with high specificity and strong binding activity, KM696 and KM697, both of which
      are of the IgM class. Variable heavy and light chain complementary DNAs of these
      two murine monoclonal antibodies were cloned and used in the construction of
      mouse/human IgG1 chimeric antibodies, KM966 and KM967, respectively, in this
      study. One of the chimeric antibodies, KM966, retained strong and specific
      reactivity with GM2 and showed the similarity of the binding activity with tumor
      cell lines to that of the original murine monoclonal antibody. Indirect
      immunofluorescence staining of tumor cell lines with the chimeric KM966 revealed
      that the antigen was expressed in substantial amounts on pulmonary tumor cells
      and leukemia cells as well as neuroectodermal origin tumor cells. When human
      serum and human peripheral blood mononuclear cells were used as effectors in
      complement-dependent cytotoxicity and antibody-dependent cell-mediated
      cytotoxicity, respectively, chimeric KM966 was fully effective in killing GM2
      expressing tumor cells. In addition, i.v. injection of chimeric KM966 markedly
      suppressed the establishment of human tumor xenografts in nude mice. Taken
      together, chimeric KM966 is the first antibody of the human IgG class to
      ganglioside GM2 and has strong antitumor activity both in vitro and in vivo. It
      is likely that chimeric KM966 will be a useful agent for passive immunotherapy of
      human cancer.

PMID- 8137258
TI  - Physiologically based pharmacokinetic model for specific and nonspecific
      monoclonal antibodies and fragments in normal tissues and human tumor xenografts
      in nude mice.
AB  - A physiologically based pharmacokinetic model to describe the biodistribution of
      a specific monoclonal antibody IgG1 (ZCE025) and its fragments (F(ab')2 and Fab)
      and of a nonspecific IgG1 (MOPC21) in normal tissues and a human colon carcinoma
      xenograft (T380) in nude mice is developed. The model simulates the experimental
      data on the concentration of these four macromolecules in plasma, urine, heart,
      lung, liver, kidney, spleen, bone, muscle, skin, GI tract, and tumor. This is the
      first such model for macromolecules with specific binding. A two-pore formalism
      for transcapillary solute exchange is used which avoids the oversimplifications
      of unidirectional transport or a single effective permeability coefficient.
      Comparison of the model with our biodistribution data shows that: (a) a
      physiologically based pharmacokinetic model for specific and nonspecific
      antibodies is able to explain experimental data using as few adjustable
      parameters as possible; (b) for antibodies and fragments, the tumor itself has no
      significant influence on the pharmacokinetics in normal tissues; and (c) the two
      pore formalism for transcapillary exchange describes the data better than a
      single-pore model without introducing extra adjustable parameters. Sensitivity
      analysis shows that the lymph flow rate and transvascular fluid recirculation
      rate are important parameters for the uptake of antibodies, while for the
      retention of specific antibodies, extravascular binding is the key parameter. A
      single-pore model could also obtain a good fit between model and data by
      adjusting two parameters; however, the estimated permeability was 1000 times
      higher than with the two-pore model, and the binding affinity was such that
      approximately five times more material was bound than free in the extravascular
      space for nonspecific antibody. Setting the binding affinity to zero or reducing
      the value of the permeability-surface area product did not allow a good fit, even
      when the lymph flow rate was varied. The present model may be useful in scaling
      up antibody pharmacokinetics from mouse to man.

PMID- 8137259
TI  - Activation of natural killer cells by mouse mammary tumor virus C4 in BALB/c and
      T-cell receptor V beta 2-transgenic mice.
AB  - Lymphocytic infiltrates of BALB/c C4 hyperplastic alveolar nodule (HAN) have
      elevated natural killer (NK) activity, which correlates positively with the
      progression of C4 HAN to tumor: C4 HAN produces an infectious mouse mammary tumor
      virus, MMTV(C4), which encodes a superantigen that activates and deletes T-cells
      with the V beta 2 segment in the T-cell receptor. In this report, NK activation
      by both MMTV(C4) and MMTV(C4) superantigen was tested. NK activity was measured
      in naive BALB/c mice, BALB/c mice depleted of V beta 2+ T-cell, or V beta 2
      transgenic mice after they received injections of either purified MMTV(C4) or
      MMTV(C4)-infected splenocytes. Elevated NK activity was observed in BALB/c mice
      receiving MMTV(C4) or MMTV(C4)-infected splenocytes. Depletion of V beta 2+, but
      not V beta 8+, T-cells by specific anti-V beta hybridoma before injection of
      MMTV(C4)-infected cells reduced but did not eliminate NK activation. NK
      activation in V beta 2-transgenic mice occurred before massive CD4 T-cell
      deletion took place and was more pronounced than that in the nontransgenic
      littermates. These results indicate that MMTV activates NK cells through
      superantigen-dependent and -independent pathways and supports the role of
      MMTV(C4) in the augmented NK activity observed in C4 HAN infiltrates. The
      progression of C4 HAN to tumor represents a model system for the analysis of how
      tumorigenesis may be affected by lesion-associated viruses.

PMID- 8137260
TI  - Isochromosome 12p-positive pineal germ cell tumor.
AB  - We report the chromosomal characteristics of a recurrent pineal non-seminomatous
      germ cell tumor in a 16-year-old male patient. This non-seminomatous tumor had
      the following components: embryonal carcinoma, teratoma, yolk sac tumor, and
      trophoblastic giant cells. Chromosome analysis showed a near-triploid karyotype
      (64 chromosomes), including two copies of an isochromosome 12p. This latter
      finding could be confirmed using 12p-specific competitive in situ hybridization
      techniques applied to cultured cells (T2219-P6 cell line) derived from the tumor.
      The present findings are in keeping with the hypothesis that isochromosome 12p
      formation is associated with the development of malignant extragonadal germ cell
      tumors.

PMID- 8137261
TI  - Aberration of genomic DNA in association with human hepatocellular carcinomas
      detected by 2-dimensional gel analysis.
AB  - Alterations of genomic DNAs in primary hepatocellular carcinomas (HCCs) were
      examined by restriction landmark genomic scanning (I. Hatada et al., Proc. Natl.
      Acad. Sci. USA, 88: 9523-9527, 1991) which is a 2-dimensional gel analysis that
      allows detection of deletion, amplification, or other rearrangements of genomic
      DNA. Sixteen HCC samples together with their normal counterparts were tested in
      this manner. Each HCC sample was micromanipulated to minimize possible carryover
      from non-malignant cells. DNAs from HCCs and their normal counterparts were
      cleaved with the restriction enzyme NotI, end labeled with 32P, and size
      fractionated by 2-dimensional electrophoresis using HinfI as the second cleavage
      enzyme. The resulting spots (about 2000) in HCC samples were compared with their
      normal counterparts. Five spots were more intense in 10-14 of the 16 HCCs (63
      88%). The intensity of several spots was reduced to about half, suggesting the
      loss of one of two alleles. Some of these decreases were observed frequently in
      different HCC samples, whereas others were sporadic. Sixty of these spots
      reproducibly decreased in > 2 cases, with 27 showing a decrease in > 50% of the
      informative cases. The highest incidence was observed in 14 of 16 samples (88%).
      No significant correlations were observed between these changes in spots and
      hepatitis B virus or hepatitis B virus infection. The use of landmarks that show
      a reproducible increase or decrease in intensity is discussed in conjunction with
      future studies of genomic alterations inherent in HCC.

PMID- 8137262
TI  - p53 mutations in lung tumors: relationship to putative susceptibility markers for
      cancer.
AB  - We have screened 108 non-small cell lung tumors for mutational alterations in the
      p53 gene (exons 5 through 8) using polymerase chain reaction and denaturing gel
      electrophoresis techniques. Thirty-four cases (32%) had aberrant band migrations.
      The following DNA-sequencing step confirmed the mutations in all these samples.
      Seventy-six % of the mutations were found at G:C base pairs. Of all the mutations
      found, 29% were GC to AT, 29% GC to TA, 15% AT to GC, 12% GC to CG, and 3% AT to
      CG. The other mutations (12%) were deletions or insertions of one base pair. The
      frequency of p53 mutations among heavy smokers was higher than in nonsmokers (P =
      0.047; odds ratio, 6.75; 95% confidence interval, 0.80-57). We examined p53
      mutations in relation to genotypes of GSTmu1 and H-ras1. Our data showed that
      nearly all heavy smokers with transversion mutations were homozygous for the
      GSTmu1 null allele (10 of 11). The frequency of such mutations was significantly
      higher for patients with two null alleles (10 of 25) than for those with at least
      one allele intact (1 of 18) (P = 0.011; odds ratio, 11.33; 95% confidence
      interval, 1.29-99.3). This study indicated that rare alleles at the variable
      number of tandem repeats region flanking the H-ras protooncogene are negatively
      associated to the presence of p53 mutations in the tumors (P = 0.009).

PMID- 8137263
TI  - K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors
      progress through different genetic lesions.
AB  - We studied K-ras and p53 gene mutations in a panel of 57 primary pancreatic
      cancers including ductal and nonductal tumors. DNAs were obtained from formalin
      fixed, paraffin-embedded material. Target sequences were amplified by polymerase
      chain reaction and analyzed by denaturing gradient gel electrophoresis and
      sequencing. Both K-ras and p53 genes were frequently mutated in ductal cancers
      (25 of 35, 71.4%; 18 of 35, 51.4%, respectively). K-ras mutations were confined
      to the second position of codon 12 where base transitions and transversions were
      equally observed. p53 changes were mainly missense mutations. Transitions and
      transversions were found equally with a prevalence of G:C-->A:T changes among
      transitions. No gene alterations were present in the 6 exocrine nonductal tumors
      and (with one exception) in the 12 endocrine tumors analyzed. Our results
      indicate that mutated K-ras and p53 genes can cooperate in the establishment of
      ductal pancreatic cancers, whereas other genetic events have to be present in
      nonductal tumors. Moreover, K-ras alterations may represent an early event in
      ductal tumorigenesis, as suggested both by the high gene mutation frequency and
      by the presence of mutations in low-grade tumors. On the contrary, p53 gene
      changes seem to represent an event required for the malignancy progression of
      ductal tumors from lower to higher grades.

PMID- 8137264
TI  - Altered expression of estrogen-regulated genes in a tamoxifen-resistant and ICI
      164,384 and ICI 182,780 sensitive human breast cancer cell line, MCF-7/TAMR-1.
AB  - A stable, tamoxifen-resistant subline, MCF-7/TAMR-1, of the human breast cancer
      cell line MCF-7 has been established in tissue culture after long-term treatment
      with 10(-6) M tamoxifen. The MCF-7/TAMR-1 cell line grows equally well in the
      presence and absence of tamoxifen, whereas the steroidal antiestrogens ICI
      164,384 and ICI 182,780 exert profound inhibitory activity on cell proliferation,
      although higher concentrations are required to inhibit these cells compared to
      the parent cells. The MCF-7/TAMR-1 cells grown in tissue culture deviate from
      parent characteristics by the complete lack of expression of progesterone
      receptors even when grown with estradiol, by an altered tamoxifen regulation of
      M(r) 52,000 cathepsin D synthesis and secretion, and by lack of tamoxifen
      stimulation of an estradiol down-regulated M(r) 42,000 protein with presumed
      growth inhibitory function. MCF-7/TAMR-1 cells are estrogen receptor positive.
      The estrogen receptors have wild-type characteristics with respect to (a) binding
      of estradiol, tamoxifen, and ICI 164,384; (b) estrogen and antiestrogen
      regulation of the estradiol-regulated proteins pS2, M(r) 61,000 alpha 1
      antitrypsin-like protein, M(r) 66,000 alpha 1-antichymotrypsin-like protein, and
      corresponding mRNAs; and (c) estrogen and antiestrogen regulation of a
      transiently transfected estrogen responsive reporter gene. We suggest that the
      lack of tamoxifen up-regulation of the M(r) 42,000 protein synthesis in MCF
      7/TAMR-1 cells may at least partly explain the resistance to tamoxifen treatment.
      The sensitivity to the growth inhibitory activity of ICI 164,384 and ICI 182,780
      may be ascribed to the maintenance of the pure antagonistic effect of these
      steroidal antiestrogens on MCF-7/TAMR-1 cells. Our results indicate that
      treatment with pure antiestrogens may be effective when patients become
      refractory to tamoxifen therapy.

PMID- 8137265
TI  - Differential sensitivity to the induction of apoptosis by cisplatin in
      proliferating and quiescent immature rat thymocytes is independent of the levels
      of drug accumulation and DNA adduct formation.
AB  - Immature rat thymocytes readily undergo apoptosis following exposure to many
      different stimuli, including agents which cause DNA damage, such as the
      topoisomerase II inhibitor etoposide and irradiation. We have shown previously
      that cells isolated from the immature rat thymus are resistant to the induction
      of apoptosis by the DNA-damaging agent cis-diamminedichloroplatinum(II)
      (cisplatin) (D. L. Evans and C. Dive, Cancer Res., 53:2133-2139, 1993). More than
      85% of these thymocytes are quiescent. Here, we demonstrate that following
      purification of the minority subpopulation of thymocytes that are proliferating,
      a 2-h exposure to 50 microM cisplatin resulted in rapid apoptosis with 66%
      apoptotic cells by 12 h. In contrast, purified, nonproliferating thymocytes
      treated with cisplatin exhibited control levels of apoptosis at 12 h. Both
      proliferating and nonproliferating thymocytes rapidly underwent apoptosis
      following continuous exposure to methylprednisolone (10 microM) and etoposide (10
      microM). The discrepancy in the levels of apoptosis seen in proliferating and
      quiescent thymocytes in response to cisplatin could not be attributed to changes
      in total cellular levels of cisplatin or to the number of DNA-platinum adducts
      which were determined, respectively, by atomic absorption spectrometry and
      competitive enzyme-linked immunoadsorbent assay. These results imply that in
      contrast to engagement of thymocyte apoptosis by methylprednisolone and
      etoposide, where apoptosis was proliferation independent, cisplatin-induced
      apoptosis depends on the presence of cells in S and G2-M phases of the cell
      cycle. Moreover, comparison of etoposide and cisplatin responses in thymocytes
      suggests that DNA damage per se may not be sufficient to induce apoptosis and
      that the type of DNA damage is important in this regard.

PMID- 8137266
TI  - Early mutational activation of the c-Ki-ras oncogene in endometrial carcinoma.
AB  - Endometrial carcinoma is theorized to arise from a series of somatic mutations
      which alter benign endometrium to progressively less differentiated histological
      lesions. One genetic alteration implicated in the carcinogenesis of endometrial
      cancer is the mutational activation of the c-Ki-ras oncogene. This study
      characterizes the frequency and the topographical distribution of activated c-Ki
      ras alleles in endometrial carcinoma. Sixty formalin-fixed, paraffin-embedded
      endometrial cancer specimens were screened for point mutations at codons 12 and
      13 of the c-Ki-ras oncogene by polymerase chain reaction and allelic specific
      oligomer dot-blot hybridization. c-Ki-ras mutations were identified in nine of 60
      (15%) tumor specimens. Five cases resulted in G to A transitions, three in G to T
      transversions, and one in a G to C transversion. These nine mutant tumors were
      analyzed by selective UV radiation fractionation and polymerase chain reaction
      for the presence of activated c-Ki-ras alleles in cell populations of various
      histological phenotype. In eight tumors, c-Ki-ras mutations were uniformly
      present in the carcinoma cells. One tumor exhibited heterogeneous mutational
      activation, with mutant c-Ki-ras alleles detected in only grade 2 carcinoma cells
      but not grade 1 carcinoma cells. c-Ki-ras mutations were present in adjacent
      hyperplasia with atypia but absent from hyperplasia without atypia. With rare
      exception, c-Ki-ras activation appears to be an early oncogenic event since it is
      homogeneously present in premalignant and malignant endometrial tissues.

PMID- 8137267
TI  - Receptor subtype expression and responsiveness to bombesin in cultured human
      bronchial epithelial cells.
AB  - We detected low level expression of the gastrin-releasing peptide and neuromedin
      B receptor mRNAs in cultures of human bronchial epithelium from 4 of 6
      individuals. Bombesin receptor subtype-3 mRNA was undetectable in these cells. An
      elevation of intracellular calcium concentration was observed in response to
      bradykinin (6 of 6) and neurotensin (1 of 5) but not to bombesin (0 of 6),
      vasopressin (0 of 6), or cholecystokinin (0 of 3). In contrast, such responses
      are frequently noted in lung cancer cell lines. Bombesin did not stimulate the in
      vitro growth of an immortalized human bronchial epithelium cell line expressing
      low levels of bombesin receptor mRNAs. We conclude that bombesin receptors are
      expressed at low levels in human bronchial epithelium cells which may acquire
      greater responsiveness to multiple neuropeptides in the course of multistep
      carcinogenesis.

PMID- 8137268
TI  - An allelotype of squamous carcinoma of the head and neck using microsatellite
      markers.
AB  - The detection in tumors of genomic regions with a high frequency of loss of
      heterozygosity has led to the localization and subsequent cloning of a number of
      tumour suppressor genes. To identify such regions involved in the development of
      squamous carcinoma of the head and neck we have analyzed 28 paired normal and
      tumor DNA samples. Using the polymerase chain reaction to amplify 50 simple
      sequence repeats or microsatellite markers we have studied all 22 q limbs and 17
      of the p limbs in 21 patients. In informative cases we observed a high incidence
      of loss of heterozygosity at five specific chromosomal regions: 3p (44%); 5q
      (43%); 9q (35%); 11q (45%); and 17p (31%). In addition, further analysis of
      tumors showing loss of heterozygosity at 5q suggests that a gene at or near the
      APC locus is involved in squamous carcinoma of the head and neck.

PMID- 8137269
TI  - Mapping of DNA alkylation sites induced by aziridinylbenzoquinones in human cells
      by ligation-mediated polymerase chain reaction.
AB  - Diaziridinylbenzoquinones such as 3,6-diaziridinyl-1,4-benzoquinone (DZQ) and its
      2,5-methyl analog (MeDZQ) require bioreductive activation in order to elicit
      their cytotoxic activities. In this study, we have mapped the intracellular
      alkylation sites induced by DZQ and MeDZQ in a single copy gene at the nucleotide
      level using ligation-mediated polymerase chain reaction. We have performed this
      analysis in two human colon carcinoma cells, one proficient (HT-29) and one
      deficient (BE) in DT-diaphorase (DTD) activity. In the DTD-proficient HT-29 cell
      line, DZQ and MeDZQ were found to alkylate both 5'-(A/T)G(C)-3' and 5'-(A/T)A-3'
      sequences. This is consistent with the nucleotide preferences observed when DZQ
      and MeDZQ are activated by purified DTD to reactive metabolites capable of
      alkylating DNA in vitro (C-S. Lee, J. A. Hartley, M. D. Berardini, J. Butler, D.
      Siegel, D. Ross, and N. W. Gibson. Biochemistry, 31: 3019-3025, 1992).
      Surprisingly in the DTD-deficient BE cell line a pattern of alkylation induced by
      DZQ and MeDZQ similar to that observed in the DTD-proficient HT-29 cells was
      observed. This suggests that reductive enzymes other than DTD can be involved in
      activating DZQ and MeDZQ to DNA-reactive species in vivo.

PMID- 8137270
TI  - Molecular cytogenetic mapping of the human melanoma antigen (MAGE) gene family to
      chromosome region Xq27-qter: implications for MAGE immunotherapy.
AB  - We have defined the chromosomal location of the human MAGE (melanoma antigen)
      gene family by polymerase chain reaction amplification of several segments of the
      MAGE genes from somatic cell hybrids containing well-defined groups of human
      chromosomes and hybrids containing human derivative chromosomes. The data show
      that the three known MAGE family members (MAGEs -1, -2, & -3) are syntenic and
      map to the human X chromosome region q27-qter. Because males and females are
      hemizygous for most X-linked genes, the frequency of antigen-loss variants for
      the MAGE system is expected to be greater in comparison to antigens encoded by
      somatic chromosomes. In this regard, we believe that patients enrolled in MAGE
      specific immunotherapy trials should be carefully monitored for the presence of
      MAGE antigen-loss variants.

PMID- 8137271
TI  - Immunoreactive hepatocyte growth factor is a strong and independent predictor of
      recurrence and survival in human breast cancer.
AB  - Hepatocyte growth factor (HGF) is a stromally derived modulator of epithelial
      cell proliferation and motility. In the present study, we have measured
      immunoreactive (ir)-HGF concentration in tumor extracts of 258 primary human
      breast cancers using an enzyme-linked immunosorbent assay and have evaluated its
      association with disease-free and overall survival. The median value of ir-HGF
      concentration was 11.0 ng/100 mg protein (range, 1.4-566.7 ng/100 mg protein).
      Correlation analyses between ir-HGF concentration and clinicopathological factors
      showed that the ir-HGF level was correlated only with tumor size (P = 0.05). No
      significant associations were found between ir-HGF content and age, menopausal
      status, nodal status, histological type, histological grade, vessel involvement,
      estrogen receptor, progesterone receptor, type of surgery, or postoperative
      adjuvant therapy. Breast cancer patients with high ir-HGF concentration had a
      significantly shorter relapse-free (P = 0.001) and overall survival (P = 0.001)
      rate when compared to those with low ir-HGF concentration at the cutoff point of
      21.7 ng/100 mg protein, which was determined in another group of 82 patients. In
      multivariate analysis, ir-HGF level was found to be the most important
      independent factor in predicting relapse-free and overall survival, of greater
      import than lymph node involvement. The putative role of HGF in breast cancer
      growth and metastasis is hereby strengthened.

PMID- 8137272
TI  - Detection of oncogene mutations in sputum precedes diagnosis of lung cancer.
AB  - The Johns Hopkins Lung Project developed an archive of sputum specimens during a
      randomized trial of lung cancer screening (1974-1982). We identified 15 patients
      from that trial who later developed adenocarcinoma of the lung. The primary lung
      carcinomas from 10 of these 15 patients contained either a ras or a p53 gene
      mutation. Using a polymerase chain reaction-based assay, stored sputum samples
      obtained prior to clinical diagnosis were examined for the presence of these same
      oncogene mutations. In 8 of 10 patients, the identical mutation identified in the
      primary tumor was also detected in at least one sputum sample. The earliest
      detection of a clonal population of cancer cells in sputum was in a sample
      obtained more than 1 year prior to clinical diagnosis. These results provide the
      basis of a novel approach for detection of lung cancer based on the evolving
      molecular genetics of this disease.

PMID- 8137273
TI  - Microsatellite instability and loss of heterozygosity in breast cancer.
AB  - Microsatellite instability (MSI) has been described in colorectal and other
      cancers. The purpose of this study was to determine the presence of MSI in breast
      cancer and to correlate its occurrence with clinicopathological parameters. For
      microsatellite markers we examined mono-, di-, tri-, and tetranucleotide repeats
      that, due to their polymorphic nature, may also be used to investigate loss of
      heterozygosity. In 20 paired breast cancer-peripheral blood DNA samples we
      identified four tumors (20%) with somatic MSI. All four tumors were stage I or
      II, grade 1 or 2, and estrogen receptor positive. To study MSI in relation to
      tumor progression we also examined paired DNA samples from two ipsilateral and
      three contralateral breast cancers, as well as two matched tumor-metastatic lymph
      node specimens. None of these seven cases showed MSI, but two of the
      contralateral tumors revealed allelic loss of polymorphic repeats. These data
      suggest that MSI is an early event in mammary tumorigenesis while loss of
      heterozygosity may occur at a later stage.

PMID- 8137274
TI  - Replication errors in benign and malignant tumors from hereditary nonpolyposis
      colorectal cancer patients.
AB  - A replication error (RER) phenotype has been documented both in sporadic
      colorectal tumors and in tumors from patients with hereditary nonpolyposis
      colorectal cancer (HNPCC). In the current study 8 of 49 (16%) sporadic colorectal
      cancers (CRCs) and 25 of 29 (86%) CRCs from HNPCC patients were found to be RER+.
      All 9 (100%) CRCs from HNPCC patients with germline mutations of the mismatch
      repair gene MSH2 were found to be RER+, while 16 of 20 CRCs from HNPCC kindreds
      unlinked or not studied for linkage to MSH2 were RER+. Corresponding analysis in
      colorectal adenomas revealed that only 1 of 33 (3%) sporadic tumors but 8 of 14
      (57%) HNPCC tumors were RER+. Moreover, RER was found in all 6 extracolonic
      cancers (endometrium, 2; kidney, 1; stomach, 1; duodenum, 1; and ovary, 1)
      derived from members of HNPCC families. These data suggest the involvement of
      mismatch repair deficiency in the premalignant stage of tumorigenesis in HNPCC
      cases, and suggest that mismatch repair genes (MSH2 or others) are defective in
      the germline of nearly all these patients.

PMID- 8137275
TI  - Expression complementary DNA library transfer establishes mrp as a multidrug
      resistance gene.
AB  - The emergence of drug-resistant cancer cells is a major obstacle to cancer
      treatment. Resistant cells often display a multidrug-resistant phenotype that
      reduces the promise of combination chemotherapy, the classic approach to the
      prevention of drug resistance. mdr1, a member of the ABC cassette superfamily of
      transporters which encodes an energy-dependent drug efflux pump, is the only gene
      known to confer the multidrug-resistant phenotype. Other multidrug resistance
      mechanisms must exist, since cell lines which have this phenotype in the absence
      of mdr1 overexpression have been described. We report here the application of a
      novel approach involving expression complementary DNA library transfer to the
      identification of drug-resistant genes. Using this approach we establish that
      mrp, a member of the ABC cassette superfamily of transporters, is capable of
      conferring a multidrug-resistant phenotype. This approach should be useful in the
      identification of other novel resistance genes.

PMID- 8137276
TI  - 1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), a
      new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat.
AB  - We have used the vitamin D analogue, 1 alpha,25-dihydroxy-16-ene-23-yne-26,27
      hexafluorocholecalcifero l (Ro24-5531), for inhibition of mammary carcinogenesis
      induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Rats were first
      treated with a single dose of either 15 or 50 mg/kg body weight NMU and then fed
      Ro24-5531 (2.5 or 1.25 nmol/kg of diet) for 5-7 months. Ro24-5531 significantly
      extended tumor latency and lessened tumor incidence as well as tumor number in
      rats treated with the lower dose of NMU. In rats treated with the higher dose of
      NMU, Ro24-5531 was fed in combination with tamoxifen; in these experiments, Ro24
      5531 significantly enhanced the ability of tamoxifen to reduce total tumor
      burden, as well as to increase the probability that an animal would be tumor free
      at the end of the experiment. In vitro, Ro24-5531 was 10-100 times more potent
      than 1,25-dihydroxyvitamin D3 for inhibition of proliferation of human breast
      cancer cell lines as well as primary cultures of cells from 2 patients with acute
      myelogenous leukemia. When fed chronically, Ro24-5531 did not elevate serum
      calcium in the present studies. We propose the new term, "deltanoids," for the
      set of molecules composed of vitamin D and its synthetic analogues, in a manner
      similar to the naming of "retinoids" for the corresponding set of molecules
      related to vitamin A.

PMID- 8137277
TI  - Effect of tumor irradiation on the uptake of lymphokine-activated killer cells in
      a murine tumor model.
AB  - Immunotherapy with lymphokine-activated killer (LAK) cells and interleukin 2 is
      one of the newer treatment modalities for cancer. This raises important questions
      concerning synergism or suppressive effects of other existing treatment
      modalities on adoptive immunotherapy with LAK cells. A tumor model with H4IIe
      hepatoma cells grown on each flank of ACI rats was developed to evaluate the
      effect of external beam irradiation of tumors on the subsequent concentration of
      LAK cells in these tumors. Tumors on one side were irradiated at 6, 12, or 16 Gy
      prior to injection of [3H]thymidine-labeled LAK cells. The effect of irradiation
      was measured as the ratio of 3H recovered in the unirradiated tumor compared to
      that in the irradiated tumor in the same animal as a function of dose and time
      after irradiation. This ratio was significantly greater than 1.0 for a radiation
      dose of 12 Gy (2.35 +/- 0.51) measured 2 days after irradiation, indicating a
      reduction in LAK cell numbers in the irradiated tumor. This reduction in LAK cell
      number persists up to at least 4 days following radiation exposure. A similar
      experiment using 125I-labeled interleukin 2 showed equal distribution in the
      irradiated and unirradiated tumors. Our data demonstrates that the concentration
      of LAK cells is markedly reduced by prior radiation, in contradistinction to
      increased uptake of immunoglobulins in irradiated tumors, as shown by others. If
      a similar reduction is observed for longer duration after radiation exposure, it
      might suggest a clinically important interaction between prior radiation exposure
      and adoptive immunotherapy.

PMID- 8137278
TI  - Expression of heme oxygenase in arsenic-resistant human lung adenocarcinoma
      cells.
AB  - We have established arsenic-resistant cells (CL3R) and their subclones from a
      human lung adenocarcinoma cell line (CL3). CL3R cells and their subclones were
      maintained in the presence of 4 microM sodium arsenite. They were 6-fold more
      resistant than CL3 cells to arsenite. Heme oxygenase was expressed in CL3R cells
      and their subclones, as demonstrated by electrophoretic analysis, Northern
      blotting, and enzyme activity assay. When CL3R15 cells were grown in arsenite
      free medium, their arsenite resistance declined in parallel with their decreasing
      heme oxygenase activity. Tin-protoporphyrin, a heme oxygenase inhibitor, was
      found to increase the toxicity of arsenic to CL3R cells. Expression of heme
      oxygenase might therefore be involved in the mechanism of arsenic resistance.
      CL3R cells were also shown to be cross-resistant to oxygen-radical generating
      agents, such as menadione and Adriamycin. Furthermore, sodium arsenite treatment
      dose-dependently increased the dichlorofluorescein fluorescence in CL3 cells but
      not in CL3R15 cells. These results suggest that heme oxygenase plays an important
      role in reducing cellular oxidants that are enhanced by sodium arsenite
      treatment.

PMID- 8137279
TI  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a potent mutagen in the mouse
      small intestine.
AB  - Mutations in long lived stem cells are critical events in carcinogenesis. The Dlb
      1 assay detects intestinal stem cell mutation at the Dlb-1 locus in Dlb-1a/b
      heterozygous mice by visualizing mutated clones of epithelial cells in situ which
      do not bind the lectin Dolichos biflorus agglutinin. We have used this assay to
      show that the food-derived heterocyclic amine 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) is a potent intestinal mutagen when
      administered either i.p. or p.o. This contrasts with the inactivity of the
      structurally related mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the
      assay which we have described previously. Immunocytochemical localization of the
      P-450 enzyme CYP1A2, which is responsible for the primary activation of these
      mutagens, shows that in untreated mice it is present in liver hepatocytes and in
      occasional villus epithelial cells but is absent from the target intestinal stem
      cell population. In addition, liver microsomes, unlike intestinal microsomes,
      were able to convert PhIP to the proximate mutagen N-hydroxy-PhIP. CYP1A2
      immunoreactivity in beta-napthoflavone-induced animals was elevated in liver
      hepatocytes and increased to a lesser extent in duodenal villus epithelial cells.
      Treatment with beta-napthoflavone produced an unexpected 46% decrease in the
      number of Dlb-1 mutations in response to PhIP. Following treatment with PhIP,
      there was no difference in the number of Dlb-1 locus mutations between the
      proximal and distal ends of the small intestine in uninduced animals, indicating
      that the bile duct is unlikely to be responsible for transport of mutation
      inducing metabolites of PhIP to the small intestine. Our results demonstrate that
      metabolic activation of an indirect acting genotoxic agent can occur at a site
      other than the target tissue, and absence of the enzymes required for activation
      of a mutagen does not necessarily protect that tissue from its genotoxic effects.

PMID- 8137280
TI  - New sublines of Chinese hamster CHL stably expressing human NAT1 or NAT2 N
      acetyltransferases or Salmonella typhimurium O-acetyltransferase: comparison of
      the sensitivities to nitroarenes and aromatic amines using the in vitro
      micronucleus test.
AB  - New sublines of Chinese hamster CHL cells stably expressing human NAT1 or NAT2 N
      acetyltransferases or O-acetyltransferase of Salmonella typhimurium were
      established, and their sensitivities to carcinogenic nitroarenes and aromatic
      amines were compared using the in vitro micronucleus test. The subline expressing
      human NAT2 N-acetyltransferase exhibited the highest sensitivity to the
      clastogenicities of 1,8-dinitropyrene and 2-nitrofluorene. These results raise
      the possibility that human NAT2 N-acetyltransferase is involved in the metabolic
      activation of 1,8-dinitro-pyrene and 2-nitrofluorene. Since human NAT2 N
      acetyltransferase exhibits a marked genetic polymorphism, the polymorphic status
      of human N-acetyltransferase could be a genetic predisposing factor to cancers
      caused by the nitroarenes. In contrast, the subline expressing O
      acetyltransferase of S. typhimurium exhibited the highest sensitivity to the
      clastogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) when the
      microsomes prepared from rat liver were present. This suggests that O
      acetyltransferase of S. typhimurium has a higher ability to activate IQ than do
      the human acetyltransferases. Acetyltransferase enzymes of human enteric bacteria
      might contribute to the metabolic activation of IQ. The sublines could provide a
      new tool for investigation of the mechanism of metabolic activation and for
      assessment of cancer risk of nitroarenes and aromatic amines to humans.

PMID- 8137281
TI  - Acceleration of mammary neoplasia in transforming growth factor alpha transgenic
      mice by 7,12-dimethylbenzanthracene.
AB  - A mouse mammary tumor virus enhancer/promoter-transforming growth factor alpha
      transgenic mouse model has been described in which mammary tumors develop (Y.
      Matsui et al., Cell, 61: 1147-1155, 1990). In Line 29, spontaneous mammary tumors
      do not develop before 300 days of age in virgin females. Herein, Line 29 virgin
      females and their nontransgenic littermates have been treated with 7,12
      dimethylbenzanthracene (DMBA) at varying dosages and times. Orogastric
      instillation of a single dose of DMBA (0.5 mg) dramatically accelerates mammary
      tumor formation when administered to 21- and 56-day-old virgin transgenic females
      compared to their nontransgenic littermates. The latency period for tumor
      formation is significantly shorter in transgenic mice treated with DMBA at 56
      days compared to transgenic mice treated with DMBA at 21 days when results are
      analyzed by time from DMBA administration. To determine whether differences in
      the proliferative state of the mammary gland may contribute to these findings,
      bromodeoxyuridine incorporation was examined in the mammary glands of untreated
      21- and 56-day-old mice. No differences in bromodeoxyuridine incorporation were
      detected between 21-day-old transgenic and nontransgenic mice. However, there was
      a marked increase in bromodeoxyuridine incorporation in the epithelial cells
      comprising the smaller ducts of 56-day-old transgenic mice compared to their
      nontransgenic littermates. These data indicate an enhancing interaction between a
      growth factor and a genotoxic carcinogen in mammary tumorigenesis and provide
      evidence that the transforming growth factor alpha transgene acts as a tumor
      promoter in this experimental model.

PMID- 8137282
TI  - Transforming growth factor-alpha and endocrine sensitivity in breast cancer.
AB  - The expression of transforming growth factor-alpha (TGF-alpha) has been evaluated
      in 51 breast cancers of known responsiveness to endocrine therapy using
      immunohistochemistry. High levels of TGF-alpha were observed in 65% of tumors and
      showed no relationship with tumor estrogen receptor or epidermal growth factor
      receptor status or Ki67 immunostaining. TGF-alpha levels did, however, relate to
      the endocrine sensitivity of the disease, with unresponsive tumors frequently
      showing high levels of TGF-alpha immunoreactivity. This relationship was observed
      in estrogen receptor-positive disease and was independent of the epidermal growth
      factor receptor status of the tumor. No quantitative association between TGF
      alpha and Ki67 immunostaining was observed in any of the subcategories of tumors.
      These data infer a role for TGF-alpha in the development of endocrine
      insensitivity in estrogen receptor-positive breast cancer by mechanisms which
      appear independent of tumor growth fraction, as determined by Ki67
      immunostaining.

PMID- 8137283
TI  - A phase I and pharmacokinetic study of intravenous phenylacetate in patients with
      cancer.
AB  - Phenylacetate has recently been shown to suppress tumor growth and promote
      differentiation in experimental models. A phase I trial of phenylacetate was
      conducted in 17 patients with advanced solid tumors. Each patient received a
      single i.v. bolus dose followed by a 14-day continuous i.v. infusion of the drug.
      Twenty-one cycles of therapy were administered at four dose levels, achieved by
      increasing the rate of the continuous i.v. infusion. Phenylacetate displayed
      nonlinear pharmacokinetics [Km = 105.1 +/- 44.5 (SD) microgram/ml, Vmax = 24.1 +/
      5.2 mg/kg/h and Vd = 19.2 +/- 3.3 L]. There was also evidence for induction of
      drug clearance. Ninety-nine % of phenylacetate elimination was accounted for by
      conversion to phenylacetylglutamine, which was excreted in the urine. Continuous
      i.v. infusion rates resulting in serum phenylacetate concentrations exceeding Km
      often resulted in rapid drug accumulation and dose-limiting toxicity, which
      consisted of reversible central nervous system depression, preceded by emesis.
      Three of nine patients with metastatic, hormone-refractory prostate cancer
      maintained stable prostatic specific antigen levels for more than 2 months;
      another had less bone pain. One of six patients with glioblastoma multiforme,
      whose steroid dosage has remained unchanged for the duration of therapy, has
      sustained functional improvement for more than 9 months. The use of adaptive
      control with feedback for the dosing of each patient enabled us to safely
      maintain stable phenylacetate concentrations up to the range of 200-300
      micrograms/ml, which resulted in clinical improvement in some patients with
      advanced disease.

PMID- 8137284
TI  - Differentiation or immune destruction: two pathways for therapy of squamous cell
      carcinomas with antibodies to the epidermal growth factor receptor.
AB  - We have carried out an immunohistochemical investigation of xenografts of
      epidermal growth factor receptor (EGFR)-overexpressing tumors that have been
      induced to regress by treatment with rat monoclonal antibodies (mAbs) to the
      human EGFR [ICR16 (IgG2a), ICR62 (IgG2b), and ICR64 (IgG1)]. When mice bearing
      xenografts of the HN5 squamous cell carcinoma were treated for 5 days with mAb
      ICR62 or ICR16, the antibodies were found to be localized uniformly on the tumor
      cell membranes. However, the foci of tumor cells that remained following
      treatment with ICR62 were smaller than with ICR16 and the former showed a more
      pronounced host mononuclear cell infiltrate. Examination of the few tumors that
      had not regressed completely and were still present as static nodules 77 days
      following the final treatment with anti-EGFR mAbs revealed significant levels of
      therapeutic mAb in the nonviable areas of the tumors. The microscopic areas of
      apparently viable tumor cells that did not stain when only secondary antibody was
      used stained positive when the sections were treated first with an anti-EGFR
      antibody. This suggests that loss of the target antigen was not a significant
      factor and that these residual cells might be eradicated by further treatment
      with mAb. Furthermore, the finding of keratinized areas in the tumors undergoing
      regression suggested that the carcinoma cells had undergone terminal
      differentiation following exposure to antibody. This possibility was supported by
      the finding that treatment of HN5 cells in vitro with mAbs ICR16, ICR62, or ICR64
      resulted in the accumulation of cells in the G0-G1 phases of the cell cycle and
      expression of the terminal differentiation markers involucrin and cytokeratin 10.
      We found no evidence of apoptosis in such cells. We conclude that antibodies
      which block the binding of EGF and transforming growth factor alpha to the EGFR
      can inhibit the growth of EGFR-overexpressing tumors by directing terminal
      differentiation and that a further therapeutic benefit may be obtained via
      immunological mechanisms with rat IgG2b mAbs such as ICR62.

PMID- 8137285
TI  - In vivo tumor growth inhibition produced by a novel sulfonamide, E7010, against
      rodent and human tumors.
AB  - The search for compounds active against solid tumors has led us to the discovery
      of a novel sulfonamide, E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-
      methoxybenzenesulfonamide), which inhibits tubulin polymerization. When
      administered orally, E7010 showed good antitumor activity against various rodent
      tumors and human tumor xenografts. In tests on mouse tumor, E7010, administered
      in doses of 25-100 mg/kg daily for 8 days, inhibited the growth of colon 38
      carcinoma inoculated s.c. in mice by 60-99%. E7010 was active against s.c.
      inoculated M5076 fibrosarcoma (75% tumor growth inhibition), s.c. inoculated
      Lewis lung carcinoma (84% increase in life span), and i.p. inoculated P388
      leukemia (118% increase in life span). In a test on rat tumor, E7010 inhibited
      the growth of SST-2 mammary carcinoma inoculated s.c. in rats by 84%. In tests on
      s.c. inoculated human tumor xenografts, E7010, when administered orally, showed a
      broad spectrum of activity. E7010 inhibited the growth of: four kinds of gastric
      cancer, H-81, H-111, SC-2, and SC-6 by 60-78%; three kinds of colon cancer, H
      143, COLO320DM, and WiDr by 58-83%; three kinds of lung cancer, LC-376, LC-6, and
      LX-1 by 63-82%; and two kinds of breast cancer, H-31 and MX-1 by 79-87%. In
      studies on drug-resistant P388 leukemia, E7010 was effective against vincristine
      resistant P388, cisplatin-resistant P388, and 5-fluorouracil-resistant P388
      sublines in mice. Because of its good activity against rodent tumors and human
      tumor xenografts, E7010 is currently undergoing Phase I clinical trials.

PMID- 8137286
TI  - Validity and usefulness of human tumor models established by intratibial cell
      inoculation in nude rats.
AB  - Intratibial injection in nude rats of 1 x 10(6) OHS, MHMX, and LOX human tumor
      cells resulted in each case in progressively growing bone tumors. When the
      diameter of the affected leg had increased by 2-3 mm, the animals were examined
      for uptake of 99mTc-methylenediphosphonate. The OHS osteosarcoma tumors caused
      sclerotic lesions with high and uniform isotope uptake, and the MHMX unclassified
      sarcoma showed a mixed pattern with both sclerotic and lytic areas, whereas the
      LOX melanoma caused lytic bone lesions with low uptake of the radionuclide. These
      findings were compared with the results of analogous investigations previously
      performed in the patients from whom the tumor lines originated. Striking
      similarities in both the morphology and the scintigraphic images were observed
      between corresponding tumors in rats and humans, with results supporting the
      clinical relevance of the model systems. When the LOX model was used for therapy
      experiments, doxorubicin had no effect on the growth of the tibial tumors, which
      in the control group appeared after a latency of 13.5 days. The alkylating agent
      mitozolomide increased the median tumor-free latency to 47 days in 7 rats, and 5
      animals did not develop tumors within the observation period of 60 days.
      Doxorubicin was ineffective also against the OHS tumor, whereas ifosfamide and
      the radionuclide 89Sr-chloride showed significant antitumor activity. The disease
      free latency increased from 20 days, in the control animals, to 45 and 28.5 days,
      respectively, in the 2 treated groups, in which 2 of 7 and 2 of 10 rats were
      without tumors at 60 days. The data demonstrate that the tibial models
      discriminated between the action of the different therapeutic agents, and suggest
      that they may be useful in selecting compounds with clinical activity against
      skeletal tumors.

PMID- 8137287
TI  - Interaction of ionizing radiation with the topoisomerase I poison camptothecin in
      growing V-79 and HeLa cells.
AB  - Interaction between gamma-rays and camptothecin (CPT) was investigated in vitro,
      using log phase HeLa-S3 cells and Chinese hamster V-79 fibroblasts. A plateau of
      toxicity was rapidly reached for both cell lines upon exposure to CPT alone,
      consistent with S-phase specificity of CPT. With synchronized HeLa cells,
      however, CPT proved cytotoxic after the middle of G1 phase. This effect was
      abolished by cotreatment with the DNA polymerase alpha inhibitor aphidicolin. CPT
      enhanced the initial slope of the radiation survival curves for asynchronous
      cells by a factor of 1.1 (HeLa) to 2.3 (V-79). This apparent radiation
      sensitization correlated with the intrinsic radiosensitivities of the drug
      surviving fractions within the different compartments of the cell cycle. There
      was no evidence of mutual potentiation of CPT and radiation in terms of survival
      as well as with regard to the formation and rejoining of DNA double-strand
      breaks. V-79 cells exhibited pronounced postirradiation recovery. In contrast,
      the response of HeLa cells to drug did not vary appreciably for over 8-h
      following radiation. This difference proceeded from differential cell cycle
      redistribution. In both cell lines, acute irradiation produced depletion of the
      G1 compartment, accumulation at the S-G2 junction, and G2 arrest in proportion to
      the gamma-ray dose. However, while radiation brought about rapid depletion of the
      S-phase compartment in V-79 cells, it induced accumulation of HeLa cells into S
      phase. As a result, the CPT-sensitive HeLa cell population, consisting of the
      early-S, mid-S, and late G1 fractions, did not vary very much after irradiation.
      Exposure to CPT under conditions of low dose rate irradiation (1 Gy/h)
      selectively reversed the radiation effect on S-phase progression in V-79 cells;
      i.e., it induced accumulation of cells in S phase in the same way as found with
      HeLa cells. Isobolic analysis of survival data consistently showed
      supraadditivity of cell killing in both cell lines upon concomitant exposure to
      CPT and low dose rate irradiation. Cytokinetic cooperation appears to be the
      major determinant of cell survival in treatments associating CPT and radiation in
      growing cells. Attempts to predict the outcome of such a combined modality thus
      should take into consideration the response of the growing fraction of each cell
      line in terms of cell cycle-regulatory processes and redistribution.

PMID- 8137288
TI  - Is tumor cell radiation resistance correlated with metastatic ability?
AB  - Patients who experience local failure following radiation treatment of epithelial
      malignancies exhibit a substantially higher rate of distant metastasis than those
      patients who achieve permanent local control. This fact has raised concern that
      the local failure to control the primary/regional tumor may serve as a marker of
      a particularly malignant neoplasm, i.e., high metastatic activity and radiation
      resistance. If this were true, there would be no gains in survival by increasing
      the efficacy of treating the primary/regional disease because the new local
      controls would develop distant metastasis. To investigate this concept, the
      relationship between distant metastasis probability and tumor cell radiation
      resistance has been studied by examining laboratory and clinical data (in vitro
      and in vivo assays) from six collaborating centers. TCD50s (radiation dose which
      inactivates half of the irradiated tumors) and incidence of distant metastasis in
      mice with local control have been evaluated for 24 murine tumor systems. SF2s
      (surviving fraction after 2 Gy) were determined in vitro for cell lines from 8
      human, 13 mouse, and 15 rat tumors/tumor sublines and the metastatic activity
      assessed after injection of the cells into syngeneic murine hosts and xenogenic
      hosts for the human tumors. SF2s of cells from carcinomas of the head/neck,
      cervix, and endometrium which were controlled locally by radiation +/- surgery
      from four centers were compared for those which did and those which did not
      metastasize. The total number of patients studied was 222. The cumulative
      distributions of SF2s of locally controlled tumors which did and did not
      metastasize were not different in each of the data sets. Similarly, there was no
      demonstrable relationship between TCD50s and metastatic frequency in local
      control mice. Furthermore, the SF2s of murine and human tumor cell lines did not
      track with metastatic activity. Radiation sensitivity of clinical and laboratory
      tumors did not correlate with metastatic activity in studies of data from six
      centers.

PMID- 8137289
TI  - Effect of 9-benzyl-9-deazaguanine, a potent inhibitor of purine nucleoside
      phosphorylase, on the cytotoxicity and metabolism of 6-thio-2'-deoxyguanosine.
AB  - 6-Thio-2'-deoxyguanosine (T-dGuo) has been reported to be both phosphorylated by
      deoxycytidine kinase and converted to 6-thioguanine by purine nucleoside
      phosphorylase (PNP). Combination of T-dGuo with an inhibitor of PNP would be
      expected to generate the 5'-triphosphate of T-dGuo and limit or prevent the
      formation of 6-thioguanosine triphosphate. Because the incorporation of 6
      thioguanine into DNA is believed to be primarily responsible for the antitumor
      activity of the thiopurines, this treatment might result in enhanced activity
      against certain tumors, particularly those of T-cell origin. We have evaluated
      the metabolic basis of this strategy by examining the effects of 9-benzyl-9
      deazaguanine (BDG), a potent inhibitor of PNP, on the metabolism of T-dGuo in CEM
      cells. The concentration of T-dGuo required to inhibit cell growth by 50% was
      approximately 50-fold greater in the presence of 8.0 microM BDG than in its
      absence. As expected, the addition of BDG to cells treated with T-dGuo prevented
      the metabolism of T-dGuo to 6-thio-guanine-containing ribo-nucleotides, but,
      unexpectedly, no 6-thio-2'-deoxyguanosine 5'-triphosphate was detected. In cells
      treated with T-dGuo plus BDG, the major phosphorylated metabolite was T-dGMP.
      These results indicated that even in the absence of PNP activity, T-dGuo cannot
      be phosphorylated directly to 6-thio-2'-deoxyguanosine 5'-triphosphate due to the
      inability of guanylate kinase to utilize T-dGMP as a substrate.

PMID- 8137290
TI  - New chimeric anti-pancarcinoma monoclonal antibody with superior cytotoxicity
      mediating potency.
AB  - The monoclonal antibodies (MAbs) 323/A3 and 17-1A both recognize a 40-kDa
      carcinoma-associated epithelial glycoprotein (EGP40). MAb 17-1A has been used in
      many therapeutic trials as an immunotherapeutic agent to combat advanced
      colorectal cancer, and about 5-10% overall responses have been observed. It has
      been shown that MAb 323/A3 has a higher affinity than 17-1A, which might be an
      advantageous feature for a therapeutic agent. In our immunohistological studies
      different reaction patterns of these two MAbs were observed, suggesting that MAb
      323/A3 reacts more intensely with carcinoma cells than MAb 17-1A. This also
      suggests that MAb 323/A3 might be a more effective immunotherapeutic tool.
      Because chimerization may reduce the immunogenicity of the murine MAb 323/A3 and
      increase the interaction with human effector mechanisms, we developed a chimeric
      form of murine MAb 323/A3. MAb 323/A3 heavy and light chain variable genes were
      cloned and grafted onto human C gamma 1 and C kappa domains, respectively. A
      chimeric antibody-producing cell line was established by transfection of the
      chimeric constructs into a nonproducing myeloma cell. The chimeric and murine
      323/A3 MAbs were evaluated for efficacy of inducing complement-mediated
      cytotoxicity (CMC) and mediating antibody-dependent cellular cytotoxicity against
      LS 180 cells derived from human colon carcinoma. Both forms were found to mediate
      similar levels of CMC in the presence of human complement; however, higher levels
      of lysis of target cells were observed with human peripheral blood lymphocytes
      when the chimeric 323/A3 was used. Chimeric 323/A3 mediated higher maximal
      cytotoxicity than chimeric 17-1A in both CMC and antibody-dependent cellular
      cytotoxicity assays and was equally active as chimeric 17-1A at 100- to 1000-fold
      lower concentrations. The superior reactivity of chimeric 323/A3 with EGP40 on
      carcinoma cells and its higher cytotoxicity-mediating capacity, compared to
      chimeric 17-1A, are important characteristics, which support further clinical
      studies with chimeric MAb 323/A3 in immunotherapy of carcinomas.

PMID- 8137291
TI  - Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene
      modified tumor vaccines.
AB  - Adenocarcinoma of the prostate is the most common cancer in men. The majority of
      cancers are discovered once they have already metastasized, and there is no
      effective therapy for prostatic cancer at this stage. The use of cytokine
      secreting tumor cell preparations as therapeutic vaccines for the treatment of
      advanced prostate cancer was investigated in the Dunning rat R3327-MatLyLu
      prostatic tumor model. IL-2 secreting, irradiated, tumor cell preparations were
      capable of curing animals with s.c. established tumors, and induced immunological
      memory that protected animals from subsequent tumor challenge. Immunotherapy was
      less effective when tumors were induced orthotopically, but nevertheless led to
      improved outcome, significantly delaying, and occasionally preventing, recurrence
      of tumors after resection of the cancerous prostate. Granulocyte-macrophage
      colony stimulating factor secreting tumor cell preparations were less effective,
      and interferon-gamma secreting cells had only a marginal effect. Induction of a
      potent immune response in tumor bearing animals against the nonimmunogenic
      MatLyLu tumor supports the view that active immunotherapy warrants further
      investigation as a potential therapeutic approach to prostate cancer.

PMID- 8137292
TI  - Activation of the leukocyte plastin gene occurs in most human cancer cells.
AB  - Examination of human neoplastic cell lines using reverse transcription-polymerase
      chain reaction (RT-PCR), Northern blotting, and protein profiling revealed that >
      90% of transformed human cell lines surveyed exhibited widely varying degrees of
      activation of the leukocyte (L)-plastin gene. By contrast, diploid cell types
      exhibited no evidence of event transient activation of this gene. The low level
      activation of the L-plastin gene, detectable only by RT-PCR, was confirmed by
      using the recombinant human L-plastin promoter to select "L-plastin positive"
      clonal subpopulations from these RT-PCR-positive cell lines. A stable cell line
      selected by this method exhibited low level constitutive synthesis of L-plastin
      mRNA and polypeptide. This cell line also exhibited the coinduction of at least
      three highly abundant new cytoplasmic proteins (M(r) 42,000, 37,000, and 34,000)
      and reduction in growth rate and saturation density. Most clonal cell lines
      derived by this selection procedure that activated the L-plastin gene exhibited a
      crisis stage that led to death of the clonal strain, a phenomenon that could be
      reproduced by induction of synthesis of recombinant L-plastin from its
      complementary DNA.

PMID- 8137293
TI  - The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a
      highly evolutionarily conserved, putative transcription factor.
AB  - The 8;21 translocation, t(8;21)(q22;q22.3), is seen only in acute myelogenous
      leukemia and is characteristically associated with the M2 subtype. Subsequent to
      our identification of the t(8;21) breakpoint region on chromosome 21, we reported
      that the translocation results in the fusion of the AML1 gene on chromosome 21
      with a novel gene on chromosome 8 which we called ETO (for eight twenty-one).
      Recently, the AML1 portion of the fusion protein has been shown to correspond to
      the DNA-binding and dimerization domains of the mouse gene, polyoma enhancer
      binding protein 2 alpha B (pebp 2 alpha B). We report here the complete sequence
      of the ETO portion of the fusion transcript as compiled from complementary DNAs
      from a t(8;21) AML patient and compare this with the ETO sequence from a mouse
      brain transcript. The deduced amino acid sequences are 99% identical. ETO has
      several features consistent with it being a transcription factor. The ETO
      sequence is different from the portion of PEBP 2 alpha B it replaces in the
      AML1/ETO fusion protein, except for their common high content of proline, serine,
      and threonine residues. Because neither the putative zinc fingers nor the TAF110
      homology domain of ETO is present in PEBP2 alpha B, one might expect functional
      differences in the ability of AML1/ETO protein to affect the levels of
      transcription of genes normally regulated to some degree by AML1 (PEBP2 alpha B)
      during myeloid differentiation. The relatively high levels of ETO in developing
      brain suggest that it could be involved in the regulation of some aspect of
      neural proliferation or differentiation.

PMID- 8137294
TI  - Analysis of yeast DNA topoisomerase II mutants resistant to the antitumor drug
      amsacrine.
AB  - Site-directed mutagenesis of regions within a plasmid-borne yeast TOP2 gene
      encoding DNA topoisomerase II and hydroxylamine mutagenesis of the entire plasmid
      were carried out, and the mutagenized plasmid DNA pools were used separately to
      transform yeast with a temperature-sensitive top2-4 mutation in the chromosomal
      TOP2 locus. By selecting transformants that grow in the presence of the antitumor
      drug amsacrine at 35 degrees C, a nonpermissive temperature for the top2-4
      allele, plasmid-borne top2 mutants expressing amsacrine-resistant and
      physiologically functional DNA topoisomerase II were readily obtained. The
      causality between amsacrine resistance and the presence of these mutations in
      yeast DNA topoisomerase II has been firmly established, and this causality in
      turn shows that, in yeast at least, DNA topoisomerase II is the only significant
      cellular target of amsacrine. Three classes of such mutants have been identified:
      one involves single or multiple changes in a sequence PLRGK-MLN located at
      positions 474-481 of yeast DNA topoisomerase II, a highly conserved motif in all
      type II DNA topoisomerases; a second involving a single mutation changing Ala642
      to threonine or glycine; and a third involving deletions of portions of the
      carboxy-terminal domain of the yeast enzyme. The nature of drug resistance of
      these different classes of mutants is discussed. The approaches used in this work
      should be readily applicable to yeast cells expressing heterologous DNA
      topoisomerases such as human DNA topoisomerase II alpha. Other DNA topoisomerase
      II-targeting drugs can also be studied in such a system.

PMID- 8137295
TI  - Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by
      comparative genomic hybridization.
AB  - Comparative genomic hybridization was applied for a comprehensive screening of
      under- and overrepresentation of genetic material in 13 autoptic small cell lung
      cancer specimens. The most abundant genetic changes include DNA losses of
      chromosome arms 3p, 5q, 10q, 13q, and 17p and DNA gains of 3q, 5p, 8q, and 17q.
      Amplification sites in these tumors were mapped to 22 chromosome bands. The most
      frequently involved band was 19q13.1 (4 cases). Bands 1p32, 2p23, 7q11.2, 8q24,
      and 13q33-34 were involved in two cases each.

PMID- 8137296
TI  - Amplification and overexpression of cyclin D1 in breast cancer detected by
      immunohistochemical staining.
AB  - Immunohistochemical staining with a monoclonal antibody against human cyclin D1
      can be used to identify breast cancers that have an amplification of the q13
      region of chromosome 11. In general, the intensity of staining is directly
      proportional to the degree of DNA amplification. In two unusual tumors, in which
      the CCND1 locus is highly amplified but staining is relatively weak, it appears
      that the DNA has undergone rearrangement and that the amplified/rearranged CCND1
      allele may have reduced transcriptional activity. More significantly, the
      immunohistochemical technique identifies additional tumors in which the cyclin D1
      gene is overexpressed with only marginal or undetectable increases in copy
      number, implying that other mechanisms can lead to deregulated expression. These
      results suggest that the frequency of overexpression is much higher than
      previously concluded from DNA-based analyses and that more than one-third of
      human breast cancers may contain excessive levels of cyclin D1. The technique we
      describe should facilitate the detection of this abnormality in a clinical
      setting and clarify its prognostic significance.

PMID- 8137297
TI  - Tumor and growth suppression of breast cancer cells by chromosome 17-associated
      functions.
AB  - Losses of functions from chromosome 17 are the most frequent genetic
      abnormalities in human breast cancer. To assess the biological role of chromosome
      17 in the development of breast cancer, we transferred a normal human chromosome
      17 to two breast cancer cell lines. No viable clone maintaining an intact
      chromosome was obtained in either MDA-MB-231 or MCF-7. Only one MDA-231/H17 clone
      contained the long arm of the transferred chromosome 17. Interestingly, this
      clone lost the ability to induce tumors in nude mice, indicating that at least
      one gene mapping to the long arm of chromosome 17 could suppress the tumorigenic
      phenotype. The p53 protein most likely was responsible for the selective loss of
      the short arm of the chromosome. Both cell lines have no wild-type p53 activity.
      MDA-MB-231 carries a single mutant TP53 allele, while MCF-7 carries two wild-type
      alleles, but p53 protein is excluded from the nucleus. Transfection in both cell
      lines of vectors expressing wild-type p53 produced only clones with
      rearrangements of the transfected TP53 complementary DNA. Thus, nonregulated
      expression of the p53 protein driven by the strong cytomegalovirus promoter may
      have triggered a rapid process of cell death. Stable expression of a mutant p53
      in MCF-7 cells proved that nuclear localization of the protein was possible;
      however, no progression toward an estrogen-independent tumorigenic phenotype was
      induced. This work indicates that functional inactivation of the wild-type p53
      protein and of the product of a gene located on 17q are essential to the
      development of breast neoplasms.

PMID- 8137299
TI  - Expression and tumorigenicity of the Epstein-Barr virus BARF1 gene in human
      Louckes B-lymphocyte cell line.
AB  - We previously showed that the Epstein-Barr virus, which encodes the BARF1 gene,
      could transform rodent fibroblasts. In this work, the expression of the BARF1
      gene was studied in the human Louckes B-lymphocyte cell line. Introduction of the
      BARF1 open reading frame under the control of the Mo-MuLV LTR promotor into
      nontumorigenic Louckes lymphoid cells led to the activation of the c-myc
      protooncogene and increased expression of the B-cell surface proteins, the
      transferrin receptor, CD21, and CD23. BARF1-expressing cells induced a diffuse
      lymphoma-like tumor in newborn rats treated with anti-thymocyte serum that was,
      however, transient and regressed after 3-4 weeks as the immune system recovered.
      The tumor induction was similar to that observed with lymphoid cell lines in
      vitro generated by infection with the B95-8 virus strain, in which lytic antigens
      are expressed at low levels. After long-term culture, Louckes cell clones lost
      expression of the BARF1 gene and were unable to induce tumors.

PMID- 8137298
TI  - Leukemia inhibitory factor in long-term adherent layer cultures: increased levels
      of bioactive protein in leukemia and modulation by IL-4, IL-1 beta, and TNF
      alpha.
AB  - In the current study, we used a monoclonal antibody-based enzyme-linked
      immunosorbent assay and bioassay to assess leukemia inhibitory factor (LIF)
      protein levels, activity, and function in supernatants of 59 adherent layers
      derived from acute and chronic myelogenous leukemia, myelodysplastic syndrome,
      and hairy cell leukemia patients and from normal controls. We demonstrate that
      biologically active LIF protein is constitutively produced and secreted by
      cultured bone marrow stromal cells from all of the studied subjects. Furthermore,
      various cytokines can alter endogenous LIF protein levels. Twenty-four h of
      exposure to recombinant human (rh) interleukin (IL) 4 (100 units/ml)
      significantly decreased LIF protein levels in adherent layer conditioned media
      [median base line level, 2.6 ng/ml; range, 1.6-8.0 ng/ml; median post rhIL-4
      exposure levels, 1.9 ng/ml; range, 0.9-5.8 ng/ml (n = 7; P = 0.022)]. In
      contrast, rhIL-1 beta and rh tumor necrosis factor alpha consistently increased
      LIF protein levels. In the samples exposed to 50 units/ml rhIL-1 beta, median
      base line LIF level was 2.6 ng/ml; median post-LIF level was 9.0 ng/ml (n = 8; P
      = 0.014). In the two samples exposed to rh tumor necrosis factor alpha (200
      units/ml), LIF levels increased from baseline levels of 2.6 and 2.7 ng/ml to
      postexposure levels of 7.7 and 12.2 ng/ml, respectively. Finally, the presence of
      LIF may be relevant to both normal and malignant hematopoietic processes as
      evidenced by: (a) LIF protein levels in adherent layer conditioned media were
      significantly elevated in samples from patients with a spectrum of hematological
      neoplasms [acute myelogenous leukemia: median level, 3.0 ng/ml (range, 1.6-11.0
      ng/ml); myelodysplastic syndrome: median level, 4.5 ng/ml (range 1.4-15.5 ng/ml);
      hairy cell leukemia; median level, 3.5 ng/ml (range 2.2-10.3 ng/ml); chronic
      myelogenous leukemia-chronic phase: median level, 4.35 ng/ml (range 0.3-19.0
      ng/ml); and chronic myelogenous leukemia-blast crisis: median level, 6.25 ng/ml
      (range 0.7-20.3 ng/ml)] as compared to samples from normal individuals (median
      level, 2.0 ng/ml; range, 0.7-4.6 ng/ml; P < 0.05); and (b) in normal controls, in
      vitro abrogation of endogenous LIF bioactivity by neutralizing antibody decreased
      the number of committed granulocyte-macrophage hemopoietic progenitors.

PMID- 8137300
TI  - Selective suppression of N-acetylglucosaminyltransferase III activity in a human
      hepatoblastoma cell line transfected with hepatitis B virus.
AB  - UDP-N-acetylglucosamine: beta-D-mannoside beta-1,4-N-acetylglucosaminyl
      transferase III (GnT-III) is a key enzyme in the branching of asparagine-linked
      oligosaccharides, which are present in surface membrane proteins of various
      tissues and in secretory glycoproteins. The activity of GnT-III was assayed in 2
      human hepatoblastoma cell lines, Huh6, which was the parental cell line, and
      HB611, which was established by transfection of 3 tandem copies of the hepatitis
      B virus genome into Huh6. A significant difference in GnT-III activity was found
      between Huh6 and HB611 (136 +/- 18.3 pmol/h/mg versus 6.7 +/- 2.4 pmol/h/mg; mean
      +/- SD, P < 0.001), whereas levels of the glycosyltransferases alpha-3-D
      mannoside beta-1,4-N-acetylglucosaminyltransferase IV, alpha-6-D-mannoside beta
      1,6-N-acetylglucosaminyltransferase-V, and beta-1,4-galactosyltransferase were
      almost the same in both cell lines. Northern blot analysis indicated that the
      decreased activity of GnT-III in HB611 was due to the decreased transcript. When
      HB611 was treated with interferon-alpha, expression of hepatitis B virus-related
      mRNA decreased, and the activity of GnT-III increased from 8.5 +/- 3.8 to 22.0 +/
      7.2 pmol/h/mg (mean +/- SD, P < 0.05). This increase was not found in Huh6.
      Binding capacity with erythrocyte phytohemagglutinin in these cells using
      fluorescence-activated cell sorter analysis was different, suggesting that the
      structure of sugar chain on the cell surface might be altered by suppression of
      GnT-III activity. This is the first report that hepatitis B virus selectively
      suppressed the GnT-III activity in hepatoblastoma cells.

PMID- 8137301
TI  - Effect of nucleolar P120 expression level on the proliferation capacity of breast
      cancer cells.
AB  - Steady-state level of nucleolar P120 protein and P120 mRNA was compared to the
      doubling time and S-phase fraction in human breast cancer cell lines growing
      exponentially and in similar cells treated with a single dose of P120 antisense
      oligodeoxynucleotides. The study included six breast cancer cell lines and one
      nontransformed breast cell line with doubling times from 1.1 to 5.5 days and with
      S-phase fractions from 35 to 9%. P120 expression level was determined by
      densitometric computerized evaluation of protein and mRNA blots and with a
      quantitative 32P-reverse transcriptase-polymerase chain reaction method developed
      for small-scale samples. In the slowest growing normal cell line, P120 expression
      level was only about 10% of the level found in the most rapidly growing cancer
      cell line. The amount of P120 mRNA was highly correlated with the amount of P120
      protein (P = 0.0001), indicating that P120 accumulation is regulated in these
      cells primarily at a transcriptional level. There was also a significant positive
      correlation between the level of P120 protein/mRNA and doubling time of cell
      lines (P = 0.0008) or percentage of S-phase cells (P = 0.210). P120 antisense
      oligomer treatment decreased the growth rate of cells in a dose-dependent manner,
      and the inhibition reached 70% at 100 microM concentration. Both P120 mRNA and
      P120 protein levels were also decreased by approximately 70% in cells treated
      with 100 microM P120 antisense oligomer. Slowly growing cells exhibited 50%
      inhibition by treatment at a proportionally lower concentration of P120 antisense
      oligomer than fast growing cells. This study shows that the expression of P120,
      measured either at the protein or the mRNA level, correlates with proliferation
      rate, identifying P120 as a cell proliferation marker.

PMID- 8137302
TI  - Clonal analysis by study of X chromosome inactivation in formalin-fixed paraffin
      embedded tissue.

PMID- 8137303
TI  - Recent studies on the metabolic activation of chemical carcinogens.
AB  - Xenobiotics continue to be found that are metabolized in mammals to electrophilic
      reactants that form covalently bound adducts to cellular DNA leading to tumor
      formation. This discussion will be limited to the following two topics:
      sulfonation in chemical carcinogenesis and endogenous etheno adducts in DNA.

PMID- 8137304
TI  - Oncogene activation and tumor suppressor gene inactivation during multistage
      mouse skin carcinogenesis.
AB  - The mouse skin multistage model of carcinogenesis is an ideal system in which to
      study questions related to the timing of oncogene activation and inactivation of
      tumor suppressor genes. A number of laboratories have shown that an early event
      associated with chemical initiation of mouse skin tumors involves activation of
      the Harvey-ras oncogene. To approach the question of timing of loss of tumor
      suppressor genes in skin carcinogenesis, we have utilized a model system
      developed by Kulesz-Martin in which cloned mouse keratinocytes were initiated
      with DMBA and variant clones with benign or malignant phenotypes were developed.
      We have generated somatic cell hybrids between the parental clone and the
      variants to study the potential loss of tumor suppressor activity during the
      progression of cells from the initiated to benign and to the malignant
      phenotypes. Somatic cell hybrids generated between the parental, normal cell
      strain (i.e., 291) and a malignant cell variant (i.e., 05), that produces
      moderately differentiated squamous cell carcinomas (SCCs), failed to produce
      tumors indicating tumor suppressor activity in the 291 cells. The 291 cells and a
      benign papilloma producing variant (i.e., 09) were able to partially suppress in
      hybrids the tumorigenicity of another malignant cell line (i.e., 03) which
      produces poorly-differentiated SCCs. Suppression of 03 tumorigenicity by the
      benign tumor cell, 09, was less than that seen with the normal cell, 291. These
      results indicated two potentially different suppressor activities were
      inactivated during progression of normal 291 to malignant 03 cells. We have also
      obtained evidence that constitutive AP-1 activity plays a role in the maintenance
      of the malignant phenotype of SCC cell lines. Two different SCC cell lines, 308
      10Gy5 and PDV, demonstrate constitutive AP-1 activity. To examine the role of
      this activity in malignant progression, we stably expressed a transactivation
      deletion mutant of the human c-jun gene in these cell lines. Expression of this
      mutant c-jun protein blocked transcriptional transactivation of AP-1 responsive
      reporter CAT constructs driven by jun, human collagenase, and the mouse
      stromelysin promoters. These malignant cells were not only inhibited in their AP
      1 transactivation response, but also in their ability to form SCCs upon s.c.
      injection into athymic nude mice. These results support the idea that inhibition
      of AP-1-mediated transcriptional transactivation is in some cases sufficient to
      suppress the tumorigenic phenotype of malignant mouse epidermal cells.

PMID- 8137305
TI  - Modulation of oxidant formation in mouse skin in vivo by tumor-promoting phorbol
      esters.
AB  - The pathways of oxidant generation in mouse epidermis were investigated by 32P
      postlabeling analysis of diastereomeric DNA adducts derived from oxidation of
      (7S,8S)-dihydroxy-7,8-dihydrobenzo(a)pyrene ((+)-BP-7,8-diol). The pattern of
      deoxynucleoside-3'-5'-bis-phosphate adducts in epidermal scrapings from female CD
      1 mice indicated that cytochrome P-450 was the major oxidant. When animals were
      pretreated with the tumor-promoting phorbol ester, tetradecanoyl phorbol acetate
      (TPA), 24 h before coadministration of TPA and (+)-BP-7,8-diol, the pattern of
      DNA adducts indicated that peroxyl radicals made a major contribution to (+)-BP
      7,8-diol epoxidation. Peroxy radical-dependent epoxidation was maximal when the
      time between the 2 TPA administrations was 24-72 h. No increase in radical
      derived adducts was observed when the non-tumor-promoting phorbol ester 4-O
      methyl-TPA was substituted for TPA. The calcium ionophore A23187 stimulated
      radical generation when substituted for the first, but not the second, TPA
      treatment. The antiinflammatory steroid fluocinolone acetonide inhibited (-)-anti
      BPDE-DNA adduct formation when coadministered with the first but not the second
      TPA treatment. In contrast, all-trans-retinoic acid inhibited (-)-anti-BPDE-DNA
      adduct formation when coadministered with the second but not the first TPA
      treatment. These findings demonstrate that tumor promoting phorbol esters
      stimulate oxygen radical generation in mouse skin and that radical generation is
      blocked by inhibitors of tumor promotion.

PMID- 8137306
TI  - Reactive oxygen species in tumorigenesis.
AB  - In this review we will summarize recent data on reactive oxygen species-induced
      mutagenesis and consider its relationship to tumorigenesis in humans. With the
      use of a single-stranded DNA template it has been possible to correlate oxygen
      radical-induced chemical alterations at specific nucleotides with the types of
      mutations that occur when these altered bases are copied by DNA polymerases. This
      has allowed us to identify the types of mutations that occur secondary to a
      variety of oxidative stresses and study several of the mechanisms by which they
      arise. The most frequent mutations that result from reactive oxygen species
      induced damage to DNA in bacteria are C to T transitions. These mutations,
      however, are not pathoneumonic for mutagenesis by oxygen-free radicals since they
      result from DNA damage caused by other genotoxic agents as well as by DNA
      polymerase errors. One type of mutation, a tandem CC to TT double substitution,
      has been shown to be induced by reactive oxygen species generated by a variety of
      systems and may be diagnostic for such damage. In studies with mammalian DNA
      polymerases, DNA damaged by reactive oxygen species yields mutations different
      from those observed in Escherichia coli. This diversity of mutagenic changes in
      these in vitro studies highlights the role of DNA replicating enzymes in
      specifying the types of mutations produced by reactive oxygen species. In
      conclusion, we will consider the role of reactive oxygen species in the
      pathogenesis of three common tumors, carcinoma of the liver, lung, and prostate
      with consideration on the possible use of antioxidant preventive therapy to slow
      tumorigenesis sufficiently to prevent clinical presentation of these cancers
      during the life span of a patient.

PMID- 8137307
TI  - Reactive oxygen-dependent DNA damage resulting from the oxidation of phenolic
      compounds by a copper-redox cycle mechanism.
AB  - Recently, copper has been shown to be capable of mediating the activation of
      several xenobiotics producing reactive oxygen and other radicals. Since copper
      exists in the nucleus and is closely associated with chromosomes and DNA bases,
      in this study we have investigated whether the activation of 1,4-hydroquinone
      (1,4-HQ) and a variety of other phenolic compounds by copper can induce strand
      breaks in double-stranded phi X-174 RF I DNA (phi X-174 relaxed form I DNA). In
      the presence of micromolar concentrations of Cu(II), DNA strand breaks were
      induced by 1,4-HQ and other phenolic compounds including 4,4'-biphenol, catechol,
      1,2,4-benzenetriol, 2-methoxyestradiol, 2-hydroxyestradiol, diethylstilbestrol,
      butylated hydroxytoluene, butylated hydroxyanisole, tert-butylhydroquinone,
      ferulic acid, caffeic acid, chlorogenic acid, eugenol, 2-acetamidophenol, and
      acetaminophen. Structure-activity analysis shows that in the presence of Cu(II),
      the DNA cleaving activity for phenolic compounds with a 1,4-hydroquinone
      structure, such as 1,2,4-benzenetriol and tert-butylhydroquinone is greater than
      those with a catechol group (catechol, 2-hydroxyestradiol and caffeic acid).
      Those compounds having one phenol group, such as eugenol, 2-acetamidophenol, and
      acetaminophen, are the least reactive. In addition, the induced DNA strand breaks
      could be inhibited by bathocuproinedisulfonic acid, a Cu(I)-specific chelator, or
      catalase indicating that a Cu(II)/Cu(I) redox cycle and H2O2 generation are two
      major determinants involved in the observed DNA damage. Using reactive oxygen
      scavengers, it was observed that the DNA strand breaks induced by the 1,4
      HQ/Cu(II) system could not be efficiently inhibited by hydroxyl radical
      scavengers, but could be protected by singlet oxygen scavengers, suggesting that
      either singlet oxygen or a singlet oxygen-like entity, possibly a copper-peroxide
      complex, but not free hydroxyl radical probably plays a role in the DNA damage.
      The above results would suggest that macromolecule-associated copper and reactive
      oxygen generation may be important factors in the mechanism of 1,4-HQ and other
      phenolic compound-induced DNA damage in target cells.

PMID- 8137308
TI  - Enzymatic repair of oxidative DNA damage.
AB  - Oxidative DNA damage, including both mutagenic and cytotoxic lesions, is
      implicated in aging and cancer. Studies of the processes which correct such
      damage in mammalian cells are, however, still in their early stages. Here we have
      summarized our recent work which demonstrates new features of mammalian oxidative
      DNA damage repair, such as (a) a functional role for poly(ADP-ribosyl)ation in
      the rejoining of DNA strand breaks and (b) the defective repair of oxidative DNA
      damage in xeroderma pigmentosum cells.

PMID- 8137309
TI  - The pathway regulating GADD153 induction in response to DNA damage is independent
      of protein kinase C and tyrosine kinases.
AB  - Treatment of cells with agents that damage DNA leads to the induction of numerous
      genes. Recent studies aimed at understanding the events preceding the
      transcriptional activation of some of these DNA damage-inducible genes in
      mammalian cells have demonstrated that various extranuclear protein kinases are
      involved in the signaling cascades. The mammalian GADD153 gene, a member of the
      CCAAT enhancer-binding protein family of transcription factors, is highly induced
      by a variety of DNA-damaging agents as well as by certain growth arrest
      conditions and oxidative stresses. We have examined the effects of numerous
      protein kinase and phosphatase inhibitors on the DNA damage-induced expression of
      GADD153, to identify the signal transduction components involved in its
      transcriptional regulation. In contrast to the transcriptional activation of c
      jun and collagenase in response to DNA damage, GADD153 induction involves neither
      protein kinase C nor tyrosine kinases but does appear to require an unidentified
      serine-threonine-kinase. Elevation of intracellular glutathione levels by
      treatment with N-acetylcysteine did not affect the methyl methanesulfonate
      induced expression of the GADD153 gene, although it did diminish cadmium chloride
      induced expression. These findings suggest that oxidative stress and DNA damage
      regulate GADD153 transcription through different pathways. Based on our findings
      and those of others with respect to other DNA damage-inducible genes, we propose
      a model depicting the complex pathways which appear to be involved in the
      regulation of mammalian genes in response to genotoxic stress and in which the
      DNA damage-induced expression of GADD153 represents a unique pathway independent
      of either protein kinase C or tyrosine kinase.

PMID- 8137310
TI  - Molecular biomarkers for aflatoxins and their application to human cancer
      prevention.
AB  - The rapidly expanding understanding of the progressive processes of
      carcinogenesis provides opportunities for the identification of molecular
      biological markers reflecting events from exposure through clinical disease.
      These molecular biological markers can be classified into categories of markers
      of exposure reflecting the dose of toxic agents, markers of effect indicating a
      biological response to exposure, and markers of susceptibility providing
      information about the inherent sensitivity of individuals to the toxic agents. By
      definition some of these markers are chemical agent specific, such as a
      carcinogen-DNA or -protein adduct, while others are biological process specific,
      such as the altered expression of a gene. This article reviews the development
      and validation of molecular biomarkers of aflatoxins using experimental and human
      population studies. The development of molecular biomarkers for aflatoxins is
      based upon the extensive research database available about their metabolism,
      macromolecular adduct formation, and general mechanisms of action. The long-term
      goal of the research described in this paper is the application of aflatoxin
      biomarkers to the development of preventive interventions in human populations at
      high risk for liver cancer.

PMID- 8137311
TI  - Biomarkers for human uptake and metabolic activation of tobacco-specific
      nitrosamines.
AB  - Tobacco-specific nitrosamines are a group of carcinogens formed from nicotine and
      related tobacco alkaloids. Two of these compounds, 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine, are believed to be involved
      as causative agents for cancers of the lung, oral cavity, esophagus, and pancreas
      associated with the use of tobacco products. The goal of the studies described
      here is to develop biomarkers which will allow us to understand the uptake,
      metabolic activation, and detoxification of these carcinogens in humans. Two
      metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its
      glucuronide, have been identified and quantified in human urine. These
      metabolites allow assessment of NNK uptake in smokers, tobacco chewers, and
      people exposed to environmental tobacco smoke. NNK and N'-nitrosonornicotine form
      hemoglobin and DNA adducts upon metabolic activation by alpha-hydroxylation.
      These adducts release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) upon hydrolysis.
      The released 4-hydroxy-1-(3-pyridyl)-1-butanone can be quantified by gas
      chromatography-mass spectrometry. A subset of smokers and most tobacco chewers
      have hemoglobin adduct levels which are higher than detected in nonsmokers. 4
      Hydroxy-1-(3-pyridyl)-1-butanone-releasing DNA adducts are higher in lung tissue
      from smokers than from nonsmokers. These data indicate that some smokers and
      tobacco chewers are capable of metabolically activating NNK or N'
      nitrosonornicotine to intermediates which bind to cellular macromolecules and
      are, therefore, at potentially higher risk for cancer development. The
      application of these biomarkers to studies on cancer induction by tobacco
      products is discussed.

PMID- 8137312
TI  - DNA markers of oxidative processes in vivo: relevance to carcinogenesis and
      anticarcinogenesis.
AB  - Understanding endogenous mechanisms of carcinogenesis through measuring oxidative
      markers has advanced greatly in the past decade, paralleling similar achievements
      in exogenous carcinogenesis through measurements of DNA-adduct markers.
      Understanding the mechanisms of genesis, metabolism, and physiological properties
      of the products of oxidative stress is essential in determining products that are
      specific molecular markers. Measurement technology allows sensitive detection,
      monitoring, and quantitation of oxidative DNA markers both locally in tissue and
      systemically in body fluids. Both approaches can be used to assess oxidative
      stress. Although measurement of markers of oxidative stress relevant to
      carcinogenesis is at an early stage of development, this approach will probably
      become an integral part of early diagnostics and the assessment of tumor
      metabolism. For comprehensive understanding of endogenous carcinogenesis,
      oxidative markers of protein and lipid damage are also necessary. A larger and
      perhaps more important application of oxidative markers is in anticarcinogenesis,
      particularly chemoprevention. Because urinary markers are a noninvasive
      methodology, they are especially appropriate for assessing and indexing the
      anticarcinogenic potential of diets and foods from modulation of the rate of DNA
      damage, which may be correlated with mutagenic and, ultimately, carcinogenic
      potential.

PMID- 8137313
TI  - Radioadaptation to the mutagenic effect of ionizing radiation in human
      lymphoblasts: molecular analysis of HPRT mutants.
AB  - A 70% reduction of HPRT- mutant frequency in radioadapted human lymphoblastoid
      cells has been reported, as analyzed by the Southern blot method (O. Rigaud et
      al., Radiat. Res., 133: 94-101, 1993). The data reported here extend the previous
      molecular analysis to a collection of 118 mutants. Structural rearrangements of
      the HPRT gene were determined using the multiplex polymerase chain reaction
      assay. This allows us to define more precisely the deleted exons in mutants and
      to ensure the absence of small alterations in exons among mutants with no
      detectable change after Southern analysis. The phenotype of these latter mutants
      is likely to be due to point mutations. Overall results of both Southern and
      multiplex polymerase chain reaction analyses confirm that the proportion of
      deletion-type mutations is decreased in adapted cells (42%) compared to that in
      mutants treated with the high dose alone (77%). Mutants with no change at the
      HPRT gene level were further characterized with respect to their HPRT gene
      expression. The vast majority of adapted mutants (86%) were still expressing
      mRNA, whereas HPRT transcripts were detected in only 56% of the mutants induced
      by the high dose alone. From these data and those reported by others, possible
      mechanisms underlying the adaptive response are proposed.

PMID- 8137314
TI  - Inflammation, chromosomal instability, and cancer: the schistosomiasis model.
AB  - Evidence is accumulating in support of a role for reactive oxygen species in the
      etiology of cancer. Inflammatory cells, such as neutrophils, macrophages, and
      eosinophils, are an important endogenous source of oxygen radicals. Stimulation
      of these cells by tumor promoters or by foreign bodies (parasites, bacteria,
      etc.) causes the release of reactive oxygen species. Laboratory studies have
      shown that genetic damage and neoplastic transformation are induced in vitro in
      cells cocultured with activated inflammatory cells. We have recently begun to
      study the role of inflammatory reactions in inducing genetic damage in a human
      population. This paper describes our initial studies of Egyptian patients
      infected with Schistosoma haematobium. This infection induces chronic
      inflammation and irritation in the urinary bladder and is associated with
      increased cancer at this site. We describe a recently completed population study
      that shows that infected individuals have elevated levels of genetic damage in
      their bladders, as measured by the exfoliated cell micronucleus test. Treatment
      that kills the parasite also reduces the micronucleus frequencies. We also
      explore the hypothesis that altered sensitivity of clones of cells in these
      patients to reactive oxygen species could be a force that drives the development
      of neoplasia by facilitating clonal expansion. Evidence is presented for the
      possible involvement of loci on chromosome 11 in controlling the level of
      chromosomal breakage caused by oxidative damage. We have shown that bladder
      carcinoma cells are sensitive to micronucleus induction by promoter-activated
      neutrophils and that they can be protected from this damage by insertion of a
      normal chromosome 11. Further work is in progress to define the source of
      chromosomal breakage in schistosomiasis patients and to begin to develop an
      understanding of the host factors protecting bladder cells in these individuals
      from genetic damage.

PMID- 8137315
TI  - Cancer screening based on genetic alterations in human tumors.

PMID- 8137316
TI  - Phenotypic and genotypic events in gastric carcinogenesis.
AB  - Two main histological variants of gastric carcinoma have been identified:
      intestinal and diffuse types. The former is preceded by a sequential chain of
      events characterized as chronic gastritis, atrophy, intestinal metaplasia,
      dysplasia, intramucosal carcinoma, and invasive neoplasia. The second type
      (diffuse) lacks well-recognized precursor changes. Genotypic events in the
      gastric precancerous process are described, but a clear model of their sequence
      and relevance is lacking. Cadherins may play a role in determining which type of
      carcinoma develops. Translocated promoter region-MET rearrangements have been
      identified since early stages of the process. p53 alterations are reported
      beginning with the dysplasia stage utilizing immunohistochemical techniques.
      Single-strand conformation polymorphism and sequencing analysis show alterations
      in early stages, especially G:C to A:T transitions.

PMID- 8137317
TI  - Experimental evidence for inhibition of N-nitroso compound formation as a factor
      in the negative correlation between vitamin C consumption and the incidence of
      certain cancers.
AB  - Ascorbic acid (ASC) consumption is negatively correlated with the incidence of
      certain cancers. This is a review and update of the theory, which has recently
      been neglected, that this negative correlation is due to ASC inhibition of in
      vivo nitrosation. The review covers the older literature on ASC inhibition of
      carcinogenesis by nitrite administered with amines or amides and more recent
      studies on ASC inhibition of nitrosation by bacteria, nitrogen oxides, and
      activated macrophages; the role of oxygen in ASC inhibition of gastric
      nitrosation; ASC inhibition of N-nitrosoproline formation in subjects from areas
      with high incidences of certain cancers; dose and temporal relationships between
      ASC and in vivo nitrosation in humans; the role of substances other than ASC in
      the inhibition of nitrosation by vegetables and fruits; and the active secretion
      of ASC into the human stomach.

PMID- 8137318
TI  - Is there a significant role for lipid peroxidation in the causation of malignancy
      and for antioxidants in cancer prevention?
AB  - alpha-Tocopherol (alpha-T) uptake and its relationship to cell proliferation and
      lipid peroxidation was studied in a baby hamster kidney cell line (BHK-21/C13)
      and its polyoma virus-transformed malignant counterpart (BHK-21/PyY cells). The
      principal findings were as follows. (a) The level of lipid peroxidation judged by
      malondialdehyde (MDA) measurement by HPLC, was higher in the transformed cells
      than in the nontransformed cells. Oxidative stress by 374 mM Fe3+/10 mM ADP
      caused a significant increase in the level of MDA of a similar magnitude in both
      cell types. Addition of 7, 14, and 21 mM alpha-T caused no diminution of the MDA
      level in the unstressed cells and abolished the increase in MDA seen in the
      stressed cells. (b) The endogenous level of alpha-T in the transformed cells was
      lower than in the nontransformed cells and all of the measurable alpha-T in these
      cells was destroyed by the oxidative stress. Supplementation of the cells with
      alpha-T caused an increase in the level of alpha-T that was proportional to the
      level of inclusion of alpha-T in the medium. (c) Growth was stimulated by 7 and
      14 mM alpha-T but not by the higher levels of inclusion in the medium. The growth
      stimulation was much larger in the transformed cells (163% of growth in the
      unsupplemented medium) than in the nontransformed cells (120%). (d) These results
      demonstrate that, in this cell system, the growth-stimulating ability of alpha-T
      is unrelated to the ability of alpha-T to control lipid peroxidation and that the
      level of peroxidation is increased in the malignant state. The difference between
      the findings reported here and earlier work showing increased levels of alpha-T
      and decreased levels of peroxidation in transformed malignant cells is discussed
      and possible explanations for it are advanced.

PMID- 8137319
TI  - Potential of food modification in cancer prevention.
AB  - This presentation focuses on research that could theoretically be applied to
      implement the strategy of general population chemoprevention. The concept is
      based on the premise of enhancing foods with known anticarcinogens through either
      agricultural methods or food-processing technologies. Two areas of our work are
      described: (a) garlic cultivated with selenium fertilization and (b) foods high
      in conjugated linoleic acid. Both selenium and conjugated linoleic acid are
      powerful chemopreventive agents in the animal tumor model. The rationale of
      delivering these two specific compounds through the food system will be
      developed. Preliminary studies will be summarized to show the feasibility of this
      approach in suppressing carcinogen-induced mammary cancer in rats. Finally, the
      advantages of using foods to provide anticarcinogens to the general population as
      part of a chemopreventive strategy will also be discussed.

PMID- 8137320
TI  - Effect of exercise intensity and duration on the induction of mammary
      carcinogenesis.
AB  - Physical activity is defined as bodily movement due to skeletal muscle
      contraction that results in quantifiable energy expenditure. Both epidemiological
      and laboratory data indicate that the level of physical activity in which an
      individual engages may affect cancer risk. Exercise is distinguished from other
      types of physical activity by virtue of the fact that the intensity, duration,
      and frequency of the activity(s) is specifically designed to improve physical
      fitness. Based on available data, a role for exercise in specifically reducing
      cancer risk has been conjectured and is referred to as the exercise-cancer
      hypothesis. However, the amount of scientific evidence in support of this
      hypothesis is still quite limited, and there are conflicting reports about the
      nature of the association. The exercise-cancer hypothesis was evaluated in two
      experimental animal models for breast cancer using treadmill running as the
      exercise paradigm. The data presented indicate that both the intensity and
      duration of exercise affect the development of experimentally induced breast
      cancer. In general, as exercise intensity increased, the likelihood that such
      physical activity inhibited carcinogenesis increased. Exercise at lower
      intensities resulted in either inhibition, no effect, or enhancement of the
      tumorigenic response depending on the duration of exercise. Inhibitory conditions
      of exercise affected both the initiation and promotion/progression stages of the
      disease process.

PMID- 8137321
TI  - Dietary modulation of pancreatic carcinogenesis: calories and energy expenditure.
AB  - Physical activity (exercise) is a lifestyle factor that has received little
      attention with regard to its role in the etiology and/or prevention of cancer.
      These studies examined the effects of treadmill exercise on the early stages of
      pancreatic carcinogenesis initiated by azaserine in rats. Male Lewis rats were
      treated with azaserine at 2 weeks of age and weaned to experimental protocols at
      3 weeks of age. Two experiments were undertaken; treadmill exercise began at 6
      weeks of age (Experiment 1) or at 13 weeks of age (Experiment 2). Rats were
      exercised for 15-20 min/day and for 3-5 days/week. Treadmill speed and angle of
      incline were adjusted to afford a range of exercise intensities. The development
      of putative preneoplastic lesions of the pancreatic acinar cells (henceforth
      termed foci) was evaluated by quantitative stereological analysis using light
      microscopy. In Experiment 1, exercise resulted in a known paradoxical reduction
      in food intake by about 15% of the intake of the sedentary group fed ad libitum.
      The burden of azaserine-induced foci was decreased by approximately 37%, and this
      was attributed to the well known effects of reduced caloric intake in these
      young, rapidly growing rats. In Experiment 2, the higher intensity treadmill
      exercise group had an increased focal burden, compared to their sedentary pair
      fed controls. Importantly, this enhancement occurred despite a reduction in food
      intake and body fat stores in this treadmill exercise group. These experiments
      demonstrate that exercise may suppress or promote carcinogenesis, depending upon
      the stage in the life cycle of the animal.

PMID- 8137322
TI  - Glutathione, ascorbate, and cellular protection.

PMID- 8137324
TI  - Cytochrome P-450 enzymes as targets for chemoprevention against chemical
      carcinogenesis and toxicity: opportunities and limitations.

PMID- 8137323
TI  - Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms.
AB  - Organic isothiocyanates block the production of tumors induced in rodents by
      diverse carcinogens (polycyclic aromatic hydrocarbons, azo dyes, ethionine, N-2
      fluorenylacetamide, and nitrosamines). Protection is afforded by alpha-naphthyl-,
      beta-naphthyl-, phenyl-, benzyl-, phenethyl-, and other arylalkyl isothiocyanates
      against tumor development in liver, lung, mammary gland, forestomach, and
      esophagus. Many isothiocyanates and their glucosinolate precursors (beta
      thioglucoside, N-hydroxysulfate) occur naturally and sometimes abundantly in
      plants consumed by humans, e.g., cruciferous vegetables. Nevertheless, the
      possible contributions of isothiocyanates and glucosinolates to the well
      recognized protective effects against cancer of high consumptions of vegetables
      are unclear. The anticarcinogenic effects of isothiocyanates appear to be
      mediated by tandem and cooperating mechanisms: (a) suppression of carcinogen
      activation by cytochromes P-450, probably by a combination of down-regulation of
      enzyme levels and direct inhibition of their catalytic activities, which thereby
      lower the levels of ultimate carcinogens formed; and (b) induction of Phase 2
      enzymes such as glutathione transferases and NAD(P)H: quinone reductase, which
      detoxify any residual electrophilic metabolites generated by Phase 1 enzymes and
      thereby destroy their ability to damage DNA. Since isothiocyanates block
      carcinogenesis by dual mechanisms and are already present in substantial
      quantities in human diets, these agents are ideal candidates for the development
      of effective chemoprotection of humans against cancer.

PMID- 8137325
TI  - Suppression of squamous cell carcinoma growth and differentiation by retinoids.
AB  - The epithelium of the oral cavity is mostly nonkeratinizing. However, it
      undergoes an abnormal squamous differentiation with keratinization during vitamin
      A deficiency or oral carcinogenesis. Vitamin A analogues (retinoids) were found
      to be effective in preventing oral premalignant lesions and second primary
      cancers in the upper aerodigestive tract. Further development of retinoids for
      prevention and therapy of squamous cell carcinoma (SCC) requires a better
      understanding of their mechanism action on the growth and differentiation of SCC
      cells. We used cultured head and neck SCC (HNSCC) cell lines as a model system.
      Treatment of HNSCC cells with beta-all-trans-retinoic acid resulted in inhibition
      of growth (proliferation and colony formation) and suppression of squamous
      differentiation to varying degrees in the different cell lines. Because some of
      the malignant HNSCC cells recapitulate the main characteristics of keratinocyte
      squamous differentiation and responsiveness to retinoids, they can serve as a
      model for investigating the mechanism underlying the effects of retinoids on cell
      growth and differentiation. It is thought that nuclear retinoic acid receptors
      (RARs) and retinoid X receptors (RXRs) mediate the above effects of retinoids by
      acting as DNA-binding transcription-modulating factors. We found that HNSCC cell
      lines express several nuclear RAR and that their level could be modulated by
      retinoids in some cell lines. An inverse relationship was found between RAR-beta
      expression and squamous differentiation. An analysis of RAR mRNA expression in
      head and neck cancer specimens revealed a decrease in RAR-beta in premalignant
      and malignant tissues relative to normal mucosa. The expression of this receptor
      increased in vivo after treatment with 13-cis-retinoic acid. These results
      implicate the loss of RAR-beta expression in the development of head and neck
      cancer and suggest that RAR-beta could serve as an intermediate marker in
      prevention trials.

PMID- 8137326
TI  - Suppression of hydroperoxide-induced cytotoxicity by polyphenols.
AB  - A variety of synthetic and dietary polyphenols protect mammalian and bacterial
      cells from cytotoxicity induced by hydroperoxides, especially hydrogen peroxide
      (H2O2). Cytotoxicity of H2O2 on Chinese hamster V79 cells was assessed with a
      colony formation assay. Cytotoxicity and mutagenicity of H2O2 on Salmonella TA104
      were assessed with the Ames test. SOS response induced by H2O2 was investigated
      in the SOS chromotest with Escherichia coli PQ37. The polyphenol-bearing o
      dihydroxy (catechol) structure, i.e., nordihydroguaiaretic acid, caffeic acid
      ester, gallic acid ester, quercetin, and catechin, were effective for suppression
      of H2O2-induced cytotoxicity in these assay systems. In contrast, neither ferulic
      acid ester-bearing o-methoxyphenol structure nor alpha-tocopherol were effective,
      indicating that o-dihydroxy or its equivalent structure in flavonoids is
      essential for the protection. There are many reports describing that polyphenols
      act as prooxidants in the presence of metal ions. Our results suggest, however,
      that they act as antioxidants in the cells, when no metal ions are added to the
      medium.

PMID- 8137327
TI  - Chemoprevention of carcinogen-DNA adducts and chronic degenerative diseases.
AB  - Molecular dosimetry techniques were exploited in order to assess the efficacy of
      experimental chemoprevention assays and to evaluate the involvement of DNA
      alterations, not only in cancer but also in other chronic degenerative diseases.
      In agreement with other protective effects previously observed in the same animal
      models, the thiol N-acetylcysteine (NAC) totally prevented or significantly
      reduced the formation of carcinogen-DNA adducts in three experimental systems in
      rats. Thus, as assessed by 32P postlabeling, supplement of the diet with NAC
      decreased both deoxyguanosine-C8-aminofluorene adducts (butanol enrichment) and
      deoxyguanosine-N2-acetylaminofluorene adducts (nuclease P1 enrichment) formed in
      rat liver following dietary administration of 2-acetylaminofluorene for 3 weeks.
      DNA adducts were detected by synchronous fluorescence spectrophotometry in rat
      liver, lung, heart, and testis following a daily i.t. instillation of
      benzo(a)pyrene for 3 consecutive days. The whole-body exposure of rats to
      mainstream cigarette smoke for 40 consecutive days resulted in the appearance of
      DNA adducts in heart, lung, and aorta, whereas no adduct was detected by
      synchronous fluorescence spectrophotometry in liver, brain, and testis. Multiple
      DNA adducts in the aorta were also measured by 32P postlabeling. Administration
      of NAC by gavage inhibited the formation of DNA adducts in all organs of rats
      treated with benzo(a)pyrene or exposed to cigarette smoke. It is of interest that
      a single chemopreventive agent can display a broad-spectrum protective ability.
      The selective localization of DNA adducts in different organs depends on
      pharmacokinetics, metabolic capacity, DNA repair efficiency, and cell
      proliferation rate. Whereas inhibition by NAC of DNA adducts in testis can be
      correlated with its demonstrated ability to prevent dominant lethal mutations, we
      raise the hypothesis that DNA adducts in lung, heart, and aorta may be
      pathogenetically associated with lung cancer, cardiomyopathies, and
      arteriosclerosis, respectively. In order to explore the involvement of molecular
      and biochemical alterations in human arteriosclerosis, we started an extensive
      collaborative project and report here preliminary data showing the presence of
      DNA adducts in aorta smooth muscle cells obtained from arteriosclerotic patients.

PMID- 8137328
TI  - Prevention of carcinogenesis by protease inhibitors.
AB  - Protease inhibitors are very effective in their ability to suppress
      carcinogenesis in many different in vivo and in vitro assay systems. One
      particularly effective protease inhibitor, the soybean-derived Bowman-Birk
      inhibitor, has been extensively studied in our laboratory. Our results have
      indicated that Bowman-Birk inhibitor suppresses carcinogenesis 1) induced by
      several different types of carcinogens, 2) in three different species (mice,
      rats, and hamsters), 3) in several different tissues/organs [colon, liver, lung,
      esophagus, and cheek pouch (oral epithelium)], 4) when administered to animals by
      several different routes (including the diet), 5) involving several different
      types of tumors (squamous cell carcinomas, adenocarcinomas, angiosarcomas, etc.)
      and 6) in different cell types [epithelial cells (in the colon, liver, lung,
      esophagus, and cheek pouch) as well as connective tissue cells (fibroblasts, both
      in vitro and those in the liver which give rise to angiosarcomas)]. Thus, the
      remarkable ability of Bowman-Birk inhibitor to serve as an anticarcinogenic agent
      has been demonstrated in a variety of different carcinogenesis assay systems.
      Although the mechanism of action of protease inhibitors as anticarcinogenic
      agents is unknown, many hypotheses have been presented. Our results suggest that
      anticarcinogenic protease inhibitors are capable of reversing the initiating
      event in carcinogenesis, presumably by stopping an ongoing process begun by
      carcinogen exposure. We have observed several effects of protease inhibitors
      which are thought to be related to their anticarcinogenic activity; these include
      1) the ability to affect the expression of certain oncogenes (e.g., c-myc and c
      fos) and 2) the ability to affect the levels of certain types of proteolytic
      activities (e.g., N-t-butoxycarbonyl-Val-Pro-Arg-7-amino-4-methylcoumarin
      hydrolyzing activity) which are elevated in carcinogen-exposed tissues. We have
      also observed other effects of anticarcinogenic protease inhibitors which may be
      related to carcinogenesis. For example, we have reported that the inhibitors can
      reduce the carcinogen-induced, elevated levels of gene amplification to nearly
      normal levels. While all of these effects of protease inhibitors may contribute
      to the prevention of carcinogenesis, the mechanism by which protease inhibitors
      prevent cancer cannot be determined with certainty until the mechanisms involved
      in cancer induction are known. While the mechanism remains unclear, it is clear
      that protease inhibitors can reverse a number of carcinogen-induced cellular
      changes which may play important roles in carcinogenesis.

PMID- 8137329
TI  - Potential use of nitroxides in radiation oncology.
AB  - The identification of radioprotectors is an important goal for those involved in
      radiation oncology and for those interested in the investigation of the
      mechanisms of radiation cytotoxicity. Recently, a new class of in vitro and in
      vivo radioprotectors, the nitroxides, has been discovered. The nitroxides are low
      molecular-weight stable free radicals which are freely membrane permeable and
      which have been shown to act as superoxide dismutase mimics. Further
      investigation of these compounds has shown that a water-soluble nitroxide,
      Tempol, protects cultured Chinese hamster V79 cells from the cytotoxicity caused
      by superoxide, hydrogen peroxide, and t-butyl hydroperoxide. Tempol and five
      other water-soluble nitroxides have also been shown to protect V79 cells against
      radiation-induced cytotoxicity. Potential mechanisms of protection by the
      nitroxides include oxidation of reduced transition metals, superoxide dismutase
      like activity, and scavenging of oxy- and carbon-based free radicals. In vivo
      studies reveal that Tempol protects C3H mice from the lethal effects of radiation
      with a dose causing 50% lethality within 30 days of 9.97 Gy and 7.84 Gy in Tempol
      treated and saline-treated mice, respectively, and a dose modification factor of
      1.3. The nitroxides represent a new class of non-thiol radioprotectors which may
      also have application as general antioxidants. Additional work is necessary to
      screen other nitroxides for in vivo radioprotection and toxicity as well as to
      fully evaluate the extent to which these compounds protect tumors.

PMID- 8137330
TI  - Serological markers of cancer and their applications in clinical trials.
AB  - Strategies for the prevention of cancer include those aimed at reducing the
      incidence of cancer (primary prevention) and cancer mortality through early
      detection of tumors (secondary prevention). The efficacy of prevention
      interventions is evaluated by clinical trials. The conduct of clinical trials is
      aided by the use of serological indicators of the carcinogenic process measured
      using plasma or red or white blood cells. The accessibility and acceptability of
      obtaining blood samples for the measurement of serological markers of
      carcinogenesis permit widespread applications in the conduct of clinical trials.
      Serological markers must be shown to be valid and reliable before their use.
      Serological markers identify a variety of stages in the process of carcinogenesis
      such as inherited or acquired susceptibility to cancer, environmental exposures
      to carcinogens, biological effects of exposures, and the presence of preinvasive
      or invasive cancer. Serological markers may be used in clinical trials to select
      high risk but disease-free individuals for participation in clinical trials based
      on susceptibility factors or carcinogenic exposures. Other uses of serological
      markers include monitoring adherence to interventions and establishing trial
      outcomes of intermediate cancer end points or incident invasive disease. Examples
      of these applications are discussed. Serological markers of carcinogenesis have
      widespread applications in clinical research and potentially for clinical
      practice. Currently, the only limitation to their widespread use is the
      availability of validated serological markers. Because of the ease and
      acceptability of their use, research into the development of serological markers
      should continue. Methods for quickly validating serological markers should be
      developed in order to aid the transition to clinical applications.

PMID- 8137331
TI  - Progress in cancer chemoprevention: perspectives on agent selection and short
      term clinical intervention trials.
AB  - The basic cancer-related chemical and biological sciences, pathology, and
      epidemiology have contributed to the understanding that antimutagenesis and
      antiproliferation are the important general mechanisms of chemoprevention and to
      the development of antimutagenic and anti-proliferative agents as potential
      chemopreventive drugs. These disciplines have also provided the biochemical and
      histopathological bases for identifying intermediate biomarkers that can be used
      as surrogate end points for cancer incidence in clinical chemoprevention trials
      and for selecting cohorts for these trials. Particularly important as
      histological biomarkers of cancer are the cytonuclear morphological and
      densitometric changes that define intraepithelial neoplasia (IEN). IEN changes
      are on the causal pathway to cancer. They may serve as target lesions in Phase II
      chemoprevention trials and as standards against which other earlier cellular and
      molecular biomarkers can be evaluated. Strategies for the clinical evaluation of
      chemopreventive agents have been defined for seven targets--colorectal, prostate,
      lung, breast, bladder, oral, and cervical cancers. Cohorts have been identified
      for short-term Phase II trials that investigate the effects of chemopreventive
      agents on IEN and on earlier biomarkers. Patients with adenomas serve as a cohort
      for trials in colon. One cohort for Phase II trials in prostate is patients with
      early stage cancers scheduled for prostatectomy; another is patients with
      prostatic intraepithelial neoplasia (without prostatic carcinoma). Patients
      treated for lung cancer are at high risk for bronchial dysplasia and second
      cancers; such patients are a cohort for Phase II trials in lung cancer.
      Presurgical breast cancer patients and patients with ductal or lobular carcinoma
      in situ are cohorts for studies in breast. Patients with superficial bladder
      cancers (Ta/T1 with or without carcinoma in situ) are cohorts for studies of
      chemoprevention in bladder, and patients with dysplastic oral leukoplakia are
      evaluated for chemoprevention of oral cancers. Cervical intraepithelial neoplasia
      is a prototype IEN, and patients with cervical intraepithelial neoplasia are a
      cohort for studies of cervical cancer.

PMID- 8137332
TI  - Retinoid chemoprevention studies in upper aerodigestive tract and lung
      carcinogenesis.
AB  - Chemoprevention is a clinical strategy to block or reverse carcinogenesis before
      the development of invasive cancer. Studies of chemoprevention in the lungs and
      upper aerodigestive tract have relied on the field carcinogenesis hypothesis,
      which predicts that diffuse epithelial injury will result from exposure of that
      epithelium to carcinogens. This hypothesis is supported by the frequent
      occurrence of multiple primary tumors within the exposed field. In addition, the
      understanding of carcinogenesis as a multistep process supports the use of
      interventions in damaged epithelium before the development of clinically invasive
      cancer. Current efforts are focused on applying to chemoprevention studies the
      increasing knowledge of the molecular events in carcinogenesis. In our program,
      clinical trials in lung and head and neck chemoprevention have focused on
      individuals with evidence of field carcinogenesis, i.e., a history of previous
      epithelial cancer or the presence of premalignant lesions. These trials include
      studies to develop clinically applicable intermediate markers of carcinogenesis
      and large Phase III trials to evaluate the efficacy of the retinoid isotretinoin
      in preventing second primary tumors following head and neck or lung cancers.

PMID- 8137333
TI  - Prevention of esophageal cancer: the nutrition intervention trials in Linxian,
      China. Linxian Nutrition Intervention Trials Study Group.
AB  - In Linxian China, the esophageal/gastric cardia cancer mortality rates are among
      the highest in the world. There is suspicion that the population's chronic
      deficiencies of multiple micronutrients are etiologically involved. We conducted
      two randomized, placebo-controlled nutrition intervention trials to test the
      effects of vitamin and mineral supplements in lowering the rates of
      esophageal/gastric cancer. In the first trial, the dysplasia trial, 3318 adults
      with a cytological diagnosis of esophageal dysplasia received daily
      supplementation with 26 vitamins and minerals in doses typically 2-3 times the
      United States Recommended Daily Allowances, or placebos, for 6 years. The second
      trial, the general population trial, involved 29,584 adults and used a one-half
      replicate of a 2(4) factorial experimental design which tested the effects of
      four combinations of nutrients: A, retinol and zinc; B, riboflavin and niacin; C,
      vitamin C and molybdenum; and D, beta-carotene, vitamin E, and selenium. Doses
      for these daily supplements ranged from 1 to 2 times the United States
      Recommended Daily Allowances, and the different vitamin/mineral combinations or
      placebos were taken for a period of 5.25 years. As part of the general population
      trial, and end-of-intervention endoscopy survey was carried out in a small (1.3%)
      sample of subjects to see if supplementation affected the prevalence of dysplasia
      and early cancer. Herein we review the methods of these trials and the results of
      the endoscopic survey. Fifteen esophageal and 16 gastric cancers were identified
      in endoscopic biopsies from the 391 subjects evaluated from two villages, and
      nearly all were asymptomatic. No significant reductions in the prevalence of
      esophageal or gastric dysplasia or cancer were seen with any of the four
      supplement groups. However, the prevalence of gastric cancer among participants
      receiving retinol and zinc was 62% lower than those not receiving those
      supplements (P = 0.09), while participants receiving beta-carotene, vitamin E,
      and selenium had a 42% reduction in esophageal cancer prevalence (0.34). We have
      reported separately that cancer mortality over the entire 5.25-year period was
      significantly reduced among those receiving beta-carotene, vitamin E, and
      selenium. The findings from the overall trial and the endoscopic sample offer a
      hopeful sign and should encourage additional studies with these agents in larger
      numbers of subjects.

PMID- 8137334
TI  - Prospects of chemoprevention of human cancers with the synthetic retinoid
      fenretinide.
AB  - Fenretinide or N-(4-hydroxyphenyl)retinamide is a vitamin A analogue synthesized
      in the United States in the late 1960s. This retinoid shows a preferential
      accumulation in breast instead of liver, is effective in the inhibition of
      chemically induced mammary carcinoma in rats, and has proved to be less toxic
      than many other vitamin A analogues. The Milan Cancer Institute has put a
      particular effort in this molecule in both the experimental and clinical fields.
      We have demonstrated, in animals and humans, that fenretinide induces a rapid
      reduction of retinol plasma concentration, that its blood levels remain constant
      during administration for as long as 5 years, and that the drug is able to
      accumulate in the human breast. To date, 2969 stage I breast cancer patients have
      been randomized to evaluate the efficacy of this retinoid to prevent
      contralateral new primaries, 709 subjects have been accrued in a prevention trial
      of basal cell carcinoma of the head and neck, and 153 patients entered a study
      the preliminary results of which already show the capability of fenretinide to
      prevent recurrences and new localizations of oral leukoplakia. Further studies on
      fenretinide will be aimed at evaluating its preventive efficacy in superficial
      bladder and prostate cancers and at exploring possible synergism with tamoxifen
      and interferons in breast cancer and skin cancer, respectively.

PMID- 8137335
TI  - The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung
      cancer in high risk populations: smokers and asbestos-exposed workers.
AB  - CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial
      in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test
      whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate
      (25,000 IU/day) can decrease the incidence of lung cancer in high risk
      populations, namely, heavy smokers and asbestos-exposed workers. The intervention
      combines the antioxidant action of beta-carotene and the tumor suppressor
      mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845
      participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants
      since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and
      former smokers (44% female). Accrual is complete everywhere except Irvine, which
      was the last center added (1991), and the safety profile of the regimen to date
      has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and
      114,100 person-years through February 1998, we expect CARET to be capable of
      detecting a 23% reduction in lung cancer incidence in the two populations
      combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male
      smokers, and asbestos-exposed subgroups, respectively. CARET is highly
      complementary to the alpha-tocopherol-beta-carotene study in Finland and the
      Harvard Physicians Health Study (beta-carotene alone) in the National Cancer
      Institute portfolio of major cancer chemoprevention trials.

PMID- 8137336
TI  - Summary of the round table discussion on strategies for cancer prevention: diet,
      food, additives, supplements, and drugs.
AB  - A Round Table Discussion was held at the Fourth International Conference on
      Anticarcinogenesis and Radiation Protection. Scientists from government and
      academia were brought together to discuss the evidence for the preventive effect
      of foods, specific nutrients and drugs against cancer, and the most appropriate
      methods of initiating nutritional cancer prevention activities to improve the
      health of the public. The panel reviewed the epidemiological evidence of the role
      of diet and specific micronutrients for the prevention of cancer, the doses of
      specific micronutrients required for preventive effects and their safety, the
      evidence for aspirin as a chemopreventive agent, the issue of foods versus
      specific micronutrients in the prevention of cancer, food safety, and approaches
      to prevention such as food fortification or dietary supplements. The remarks of
      the panel members are summarized.

PMID- 8137337
TI  - Pharmacokinetics and cancer: successes, failures and future prospects.
AB  - Cancer pharmacokinetics has made an enormous contribution to the development and
      optimization of cancer therapy. While consolidating its position and subjecting
      itself to prospective clinical trials in areas of established pharmacology, it
      needs also to keep constantly on the move in order to respond to the challenging
      demands of more futuristic approaches. Antibodies, cytokines, nucleic acid drugs
      and therapeutic genes will be metabolized and excreted and will in addition
      display special difficulties in terms of tissue and cell uptake. Pharmacokinetic
      considerations must accompany all new experimental therapies for scientific
      reasons as well as to fulfil regulatory requirements (Peck et al, 1992). The very
      latest approaches will understandably be seen by many practising clinicians as
      science fiction--for example obtaining a genetic fingerprint of a patient's
      tumour in order to guide corrective therapy, whether it be based on a chemical
      drug or a replacement gene. But it is from such speculative attempts that the
      real breakthroughs of the future may follow and pharmacokinetic/pharmacodynamic
      studies are essential to these efforts. In terms of the role of pharmacokinetics
      and pharmacodynamics in day to day management of individual patients, we do need
      to be more pragmatic. We must address tough questions such as: Can the assays be
      conducted on a routine basis? Do the measurements affect treatment outcome? Are
      they cost effective? Will they actually be used by clinical and nursing staff in
      a busy hospital environment? There is ample evidence in the following pages that
      pharmacokinetics will continue to prove vital to support both routine patient
      management and the exciting new approaches to cancer therapy.

PMID- 8137338
TI  - Pharmacokinetic principles of locoregional chemotherapy.
AB  - The rationale for regional chemotherapy is based on the premise that certain
      tumours are confined to compartments within the body for a large part of their
      natural history and that the dose-response curves for most cytotoxic drugs are
      steep. If the drug can be introduced locally, then much higher drug
      concentrations can be achieved at the site of bulk tumour and the prospects of
      drug induced cytotoxicity enhanced. The general pharmacokinetic principle guiding
      regional chemotherapy is that the rate of drug clearance from the local
      compartment (peritoneal and pleural cavities, vascular territories) is smaller
      than total body clearance, creating a concentration differential in favour of the
      local compartment harbouring the majority of the cancer. There is good evidence,
      under certain situations, that pharmacokinetic advantage can translate to
      clinical advantage.

PMID- 8137339
TI  - Clinical pharmacokinetics of anti-metabolites.
AB  - Anti-metabolites are among the most important agents used in cancer chemotherapy.
      Ara-C, the thiopurines and MTX are active drugs for both induction and
      maintenance chemotherapy of childhood and adult leukaemia, while the new
      adenosine analogues are active against hairy cell leukaemia, with promising
      activity against other malignancies such as malignant lymphomas. Methotrexate and
      5FU are being used in the treatment of several solid malignancies. Recent
      advances in the clinical pharmacology of widely used antimetabolites have shown a
      relationship among dose, plasma concentrations and clearance with the toxicity
      and anti-tumour activity. Thus, it has been shown that adaptative control of 5FU
      administration is possible, limiting the toxicity of this drug. Recent advances
      in the pharmacogenetics of, for example, 6MP and 5FU will possibly enable
      researchers to identify patients who may have an increased risk of toxicity. For
      ara-C, some evidence has been obtained to identify populations at risk of no
      response. In addition, for most anti-metabolites, convincing evidence of their
      intracellular (intratumour) metabolism has been obtained, thus making it possible
      to identify patients who are likely to respond to treatment. These studies (eg
      accumulation of active metabolites such as ara-CTP, thioguanine nucleotides,
      FdUMP, MTX-polyglutamates; and inhibition of target enzymes such as thymidylate
      synthase) have made it possible to develop the basis of biochemical modulation-
      that is, specific manipulation of intracellular metabolism of the drug. It is
      anticipated that new technical developments in molecular biology, biochemistry,
      cell biology and immunology will make it possible to improve the identification
      of resistant patients in order to modulate specifically drug metabolism in the
      tumour cells. Biochemical modulation has been successful in achieving significant
      improvements in treatment and currently is a keystone in cancer chemotherapy.
      Together with the development of promising new anti-metabolites, biochemical
      modulation (with other drugs, biologicals) will be a major strategy for the
      future.

PMID- 8137340
TI  - Pharmacokinetics of alkylating agents.
AB  - Alkylating agents have been used for over 30 years in the treatment of malignant
      disease. Because of their very reactive nature, studies of their intermediate
      metabolism have been difficult. However, this is now possible with modern
      analytical techniques. Further understanding of their metabolism and
      pharmacokinetics should lead to a more rational use in the clinic.

PMID- 8137341
TI  - Platinum complexes in cancer medicine: pharmacokinetics and pharmacodynamics in
      relation to toxicity and therapeutic activity.
AB  - The study of the pharmacokinetics and pharmacodynamics of platinum based anti
      cancer drugs has done much to direct their development, at both preclinical and
      clinical levels. The clinical development of cisplatin depended on an
      understanding of its mechanism of action. The amelioration of the renal toxicity
      of cisplatin with sodium chloride infusion and forced diuresis is thought to rely
      on a common ion effect to suppress the formation of aquated species in the renal
      tubule. Studies of the modulation of cisplatin toxicity with other agents have
      followed, although none has yet achieved widespread acceptance. Following the
      demonstration of the important clinical role for cisplatin, studies of the
      relationship between toxicity and the reactivity of the leaving groups led to the
      development of the less toxic but equally effective analogue, carboplatin. The
      clinical development of carboplatin has in turn been strongly influenced by the
      studies of its pharmacokinetics, with pharmacokinetically guided dosing now being
      standard in many cancer centres and also being widely used in current clinical
      trials. Pharmacokinetic studies in animals have demonstrated that it is possible
      to make analogues that have good oral bioavailability. Apart from the convenience
      of oral administration, there is also the suggestion that these molecules may
      possess activity against certain cisplatin resistant cell lines. For the future,
      the development of sensitive methodologies whereby the exact types of platinum
      DNA adducts formed can be characterized may allow the reason for the remarkable
      anti-tumour activity of these complexes to be elucidated and further, more
      selective compounds to be designed. The history of the development of platinum
      compounds emphasizes the importance of performing intensive pharmacokinetic,
      pharmacodynamic and mechanistic studies in concert with the clinical development
      of any class of agents.

PMID- 8137342
TI  - Pharmacokinetics and metabolism of anthracyclines.
AB  - The anthracycline antibiotics constitute a major series of anti-cancer drugs, the
      best known and most widely used being doxorubicin. Among hundreds of analogues,
      only a few have reached routine clinical use. Their main metabolic feature is the
      reduction of a ketone group to an hydroxyl group, giving an -ol derivative
      generally less active than the parent compound. Anthracyclines are characterized
      by a rapid distribution phase and a slow elimination phase. The successive half
      lives of doxorubicin in plasma are about 5 minutes, 1 hour and 30 hours. Its
      total plasma clearance is about 30 l/hr/m2, and its total volume of distribution
      at steady state is approximately 15 l/kg. Anthracyclines are excreted mostly
      through bile, and special care must be taken with their use in patients with
      hepatic dysfunction. The new anthracyclines of clinical interest in solid tumours
      (epirubicin, pirarubicin) are more lipophilic than doxorubicin and have a higher
      volume of distribution and an increased total plasma clearance. Idarubicin is
      active in leukaemia rather than against solid tumours, and an oral form is
      available. Because of their high tissue fixation, these new anthracyclines are of
      particular interest for locoregional therapy, especially through the hepatic
      artery. Myelosuppression is the dose-limiting toxicity of anthracyclines and is
      related to drug exposure, so that pharmacokinetic-pharmacodynamic relationships
      have been clearly established for these drugs. A new subfamily, characterized by
      a morpholino group, presents very original features such as direct covalent
      linking to DNA after cytochrome P450 activation. These molecules are active at
      100-fold lower concentrations than the conventional anthracyclines and are
      currently in clinical trials.

PMID- 8137343
TI  - Clinical pharmacokinetics and pharmacodynamics of epipodophyllotoxins.
AB  - The disposition of epipodophyllotoxins is understood in considerable detail
      compared to other anti-cancer agents. Recent insights into the pharmacokinetic
      pharmacodynamic relationship between etoposide and teniposide systemic exposure
      and both toxicity and outcome offer a basis for more rational approaches to drug
      dosage, with the emphasis on systemic exposure achieved, rather than the amount
      of drug administered per body surface area. Recent studies indicate that chronic-
      for example 21 days--administration of low dose etoposide may be a more effective
      dosage schedule for some malignancies. Until the longer term toxicities have been
      assessed, enthusiasm for this new dosage schedule must be tempered by the
      potential for greater risk of second malignancies, which has been associated with
      the frequent--weekly or twice weekly--administration of larger intravenous doses.
      Measurement of active intracellular drug (and metabolite) concentrations have
      identified correlations for toxicity and clinical efficacy for such drugs as
      methotrexate, 6-mercaptopurine, cytarabine and platinum complexes (Plunkett et
      al, 1985; Reed et al, 1987; Lennard and Lilleyman, 1989; Whitehead et al, 1990).
      Similar approaches are feasible for the epipodophyllotoxins and may provide an
      additional strategy for further improvement in the use of these active compounds.

PMID- 8137344
TI  - Pharmacokinetics and metabolism of vinca alkaloids.
AB  - The anti-mitotic vinca alkaloids, vinblastine, vincristine, vindesine and
      navelbine, are widely used both as single agents and in combination with other
      antitumour drugs in cancer chemotherapy. Data on clinical pharmacokinetics
      following intravenous bolus injection, continuous infusion and oral
      administration show that vinca alkaloids are characterized by a large apparent
      total distribution volume, rapid total plasma clearance and a long terminal half
      life. Faecal excretion is the main elimination route of vinca alkaloids in
      humans. Urinary excretion of these agents is generally low. Moreover, vinca
      alkaloid pharmacokinetics are time- and dose-dependent and show large inter- and
      intraindividual variability. When studied in various in vitro hepatic models
      (freshly isolated human and animal hepatocytes in suspension and in primary
      culture, isolated liver perfusion and human hepatic microsomal fractions), the
      vinca alkaloids were extensively biotransformed into a number of metabolites
      which have not yet been identified structurally. Incubation of vindesine and
      vinblastine with a library of human liver microsomal fractions demonstrated the
      involvement of the human hepatic cytochromes P4503A in the biotransformation of
      these and probably other vinca alkaloids. This finding is of great importance
      with regard to possible drug interactions between vinca alkaloids and other drugs
      administered concurrently in combination cancer chemotherapy.

PMID- 8137345
TI  - New approaches in preclinical and clinical pharmacokinetics.
AB  - Pharmacokinetic studies are now playing an increasingly important part in the
      preclinical and clinical development of new anti-tumour agents. Preclinically,
      pharmacokinetic, metabolism and toxicological investigations are being integrated
      and used for the rational selection of new agents with a favourable
      pharmacological profile. More importantly, this approach should reduce the chance
      of developing a lead compound that may display idiosyncratic and unpredictable
      behaviour in patients. Pharmacokinetic studies are also invaluable in identifying
      potential problems due to species differences in drug handling and should help
      improve the quality, reliability and predictability of toxicokinetic
      investigations in experimental animals. Importantly, pharmacokinetic studies
      involving PGDE, MTSE and Bayesian approaches are increasingly being used to guide
      dose escalation in early clinical trials. It is likely that these methodologies
      will evolve further as experience with them develops, and this should lead to
      improvements in the conduct and scientific quality of phase I/II trials. It
      therefore behooves the clinician and clinical pharmacologist to pay special
      attention to the design and implementation of pharmacokinetic studies in early
      clinical trials.

PMID- 8137346
TI  - Pharmacokinetics of high molecular weight agents.
AB  - The various high molecular weight agents discussed in this chapter are at
      different stages of gestation, but as yet none have had a clear clinical impact
      despite many years of scientific effort. The problems that have been encountered
      along the way for many agents are similar: how to avoid reticuloendothelial
      trapping and how to achieve adequate penetration of a macromolecule into a solid
      tumour. The solutions offered to these problems are as diverse as the agents
      themselves, and, as a spin-off, our understanding of tumour cell behaviour (eg
      endocytosis) has improved. For many of the systems discussed, it remains unclear
      whether this approach is just a complex way of administering a continuous low
      dose infusion of the cytotoxic component. Advances in this field appear to have
      accelerated over the last 2-3 years, and it should not be much longer before
      these scientifically pleasing and elegant systems are shown to have clinical
      advantages over conventional cytotoxic drug delivery.

PMID- 8137347
TI  - Pharmacokinetics of anti-endocrine agents.
AB  - Endocrine therapy plays a major part in the systemic treatment of common cancers
      such as breast and prostatic carcinomas and some gynaecological malignancies.
      Although more than two million women have been treated with the anti-oestrogen
      tamoxifen, its disposition is still not completely understood. The absorption
      fractions for tamoxifen and the progestin drugs are uncertain. Many studies
      evaluating the plasma pharmacokinetics of tamoxifen and progestin drugs used
      blood sampling times that may have been too short to allow the determination of
      the terminal half-life with certainty. For most drugs, information on tissue
      concentration in general and tumour concentration in particular is lacking.
      Clinical results obtained with combined treatment may have been confounded by
      drug interactions, as exemplified by use of the enzyme inducer aminoglutethimide.
      Aims for further studies will be to compare tissue distribution and tumour
      distribution in relation to treatment response and to evaluate drug interactions.
      Increasing use of tamoxifen in premenopausal women highlights the need to study
      long term effects with special regard to possible teratogenicity.

PMID- 8137348
TI  - Pharmacokinetics and early clinical studies of selected new drugs.
AB  - The five examples given here illustrate new cytotoxic agents at different stages
      of evaluation. In all cases, considerable effort has gone into detailed
      pharmacokinetic studies conducted before and during the clinical phase I studies.
      Has this effort contributed significantly to the development of these agents? At
      present, it has to be said that the contribution made in the case of these
      particular agents has been modest. For the anthrapyrazoles, the availability of
      the pharmacokinetic data did not permit a pharmacokinetically guided dose
      escalation to be performed because of non-linear kinetics, and a similar comment
      can be made for rhizoxin, since the human plasma AUC values at the MTD were much
      lower than in the mouse. For the camptothecin analogues, a detailed knowledge of
      the kinetics of the closed and open forms of the various agents did not influence
      the way in which the studies were conducted, nor did pharmacokinetic information
      appreciably do so for EO9, although some comfort was gained by clinical
      investigators when the short half-life seen in preclinical species was also
      observed in humans. For suramin, therapeutic drug monitoring is clearly
      essential, although toxicity remains a problem. Of course, a proper understanding
      of the pharmacokinetics and metabolism of these agents greatly improves the
      interpretation of the clinical observations made and is often critical in
      planning the next stages of development. This is more clearly seen with agents
      that have unusual forms of toxicity, such as flavone acetic acid, for which the
      achievement of notional target concentrations is a key element in clinical trials
      (Kerr et al, 1987; Maughan et al, 1992). Moreover, as reviewed elsewhere (Graham
      and Workman, 1992; see also Graham and Kaye, this volume), there are several
      other instances where pharmacokinetically guided dose escalation has greatly
      improved the conduct of a phase I study. Good examples of this are
      iododoxorubicin (Gianni et al, 1990), mitotic inhibitor CI-980 (Brodfuehrer et
      al, 1992) and DNA intercalator CI-958 (Whitfield et al, 1992). Not surprisingly
      then, pharmacokinetics can help guide early clinical studies of some compounds
      but not others and whether they will be of value can only be determined by
      carrying out the pharmacokinetic measurements. The real value of the
      pharmacokinetic studies for the five compounds reviewed may not yet have been
      seen. Interpatient variations in drug handling can play a major part in
      determining levels of anti-tumour activity as well as toxicity.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8137349
TI  - New techniques in the pharmacokinetic analysis of cancer drugs. I. Mass
      spectrometry: recent technical developments and applications in cancer
      chemotherapy.
AB  - Mass spectrometry has emerged as a powerful tool for studying the fate of drugs
      in living organisms, especially when used in conjunction with new techniques of
      ionization, such as fast atom bombardment or the ion spray technique, and
      efficient detectors. New ionization techniques have led to the development of
      high performance liquid chromatography-mass spectrometry interfaces that combine
      the separation efficiency of HPLC and the power of mass spectrometry for
      determination of the molecular weight of complex macromolecules and
      identification of the structure of drugs and their biotransformation products.

PMID- 8137350
TI  - New techniques in the pharmacokinetic analysis of cancer drugs. II. The
      ultratrace determination of platinum in biological samples by inductively coupled
      plasma-mass spectrometry.
AB  - The use of ICP-MS and its various sample introduction techniques has great
      potential in extending the time scale of study for the pharmacokinetics of
      platinum containing anti-tumour drugs. Electrothermal vaporization ICP-MS can be
      used to measure very small samples with very low concentrations. Speciation
      studies of platinum in tissues can be carried out with HPLC-ICP-MS over longer
      time periods. Finally, LA-ICP-MS is potentially useful for studying the spatial
      distribution of platinum in tissues and tumours.

PMID- 8137351
TI  - New techniques in the pharmacokinetic analysis of cancer drugs. III. Nuclear
      magnetic resonance.
AB  - Nuclear magnetic resonance spectroscopy and imaging are non-invasive methods for
      monitoring the metabolism and distribution of anti-cancer drugs in tumours or
      other tissues. 19F NMR provides the easiest approach but requires a "built-in"
      fluorine atom in the drug of interest (eg 5-fluorouracil) or the incorporation of
      fluorine with minimal perturbance of a drug's properties. 2H NMR has also been
      used but has an effective sensitivity about 10- to 100-fold less than 19F. 1H and
      13C are likely to be useful as non-perturbing NMR probes for future
      pharmacokinetic studies. The method is intrinsically insensitive, with a
      detection limit in the range of 0.01 to 0.1 mmol for fluorinated drugs.
      Techniques for absolute quantitation and for reliable localization to specific
      tissues and tumours are now available but have only rarely been applied in
      pharmacokinetic studies in the current literature. The incorporation of in vivo
      NMR measurements in a drug development programme should help to explain the
      differences found between drug activity in vitro, in solid animal tumour models
      and in cancer patients. It may also be possible to optimize drug selection or
      mode of administration for an individual patient.

PMID- 8137352
TI  - New techniques in the pharmacokinetic analysis of cancer drugs. IV. Positron
      emission tomography.
AB  - Positron emission tomography is a powerful tool for the absolute quantification
      of injected positron emitting radiotracer concentration within tissues in vivo.
      Very detailed spatiotemporal data can be obtained without biopsy sampling. Most
      chemotherapeutic agents can be labelled with a positron emitter, and human tissue
      and tumour pharmacokinetics can be obtained non-invasively. Its main limitations
      are the inability to discriminate metabolites, the short half-life of the
      isotopes used and the specialized equipment required. Despite this, PET has the
      potential to make a major contribution in the study of the pharmacokinetics of
      anti-cancer drugs.

PMID- 8137353
TI  - Pharmacodynamic-pharmacokinetic relationships and therapeutic drug monitoring.
AB  - Pharmacokinetic-pharmacodynamic studies are becoming increasingly important in
      the development of new anti-cancer drugs. The Hill maximal effect model describes
      a sigmoidal dose-response relationship and has been applied to analyses of both
      haematological and non-haematological toxicity. This review discusses several
      approaches to population pharmacodynamics, including the two stage, NONMEM, and
      non-parametric approaches. Pharmacodynamic models for the haematological toxicity
      of amonafide, carboplatin, doxorubicin, etoposide, HMBA and menogaril are
      discussed, as are models for non-haematological toxicity. Adaptive control
      methods and therapeutic drug monitoring are useful in dosing drugs with narrow
      therapeutic windows, but the indications for using such strategies should be
      carefully selected. Models for 5FU, HMBA, methotrexate, 6-mercaptopurine,
      carboplatin and etoposide are discussed. Limited sampling strategies can
      facilitate the completion of pharmacokinetic studies and should be developed
      during phase I testing of new compounds. A new area of future importance is the
      investigation of drugs with active metabolites, such as the anthracyclines and
      amonafide.

PMID- 8137354
TI  - The role of pharmacogenetics in chemotherapy: modulation of tumour response and
      host toxicity.
AB  - What may appear to be a strategy for investigating pharmacogenetic variation must
      be seen in the context of an evolving understanding of the molecular biology of
      drug metabolism. New biochemical and analytical techniques permit the
      determination of mechanisms of drug action and the molecular biology of host and
      tumour factors influencing that action. However, the only example of the
      application of pharmacogenetics in cancer chemotherapy is that of 6MP in the
      treatment of ALL. This was based on a solid understanding of both the metabolism
      of the drug and therapeutic response and the ability to measure the polymorphic
      enzyme in erythrocytes. Identification of the gene responsible for this enzyme is
      thought to be near, with subsequent identification of mutant forms completing the
      pharmacogenetic story for this drug. However, pharmacogenetics appears to be an
      important component in the variability of both toxicity and tumour response for
      several chemotherapeutic agents. Determination of the complete molecular basis
      for this variation will no doubt make a major contribution to the increased
      understanding of host and tumour pharmacology, with the ultimate aim of
      optimization of therapy.

PMID- 8137355
TI  - An NMR spectroscopic and conformational study of 12 pseudo-disaccharides (D
      glucopyranosyl-5a-carba-D- and -L-glucopyranoses).
AB  - NMR spectroscopic data for 12 pseudo-disaccharides of the general structure:
      (alpha or beta)-D-glucopyranosyl-(1-->chi)-5a-carba-(D or L)-glucopyranose,
      representing analogues of laminaribiose (beta-D-Glc p, chi = 3), cellobiose (beta
      D-Glc p, chi = 4), and maltose (alpha-D-Glc p, chi = 4) are presented. The
      assigned NMR chemical shifts together with NOE difference measurements in
      association with calculations applying the HSEA force field combined with Monte
      Carlo simulations have been used to assess the conformational preferences of the
      investigated compounds. The results are correlated with general structural
      features involved in the interactions between monosaccharide units of
      oligosaccharides.

PMID- 8137356
TI  - Synthesis of the globotetraose tetrasaccharide and terminal tri- and di
      saccharide fragments.
AB  - The 2-(trimethylsilyl)ethyl (TMSEt) beta-glycosides of globotetraose [beta-D
      GalNAc-(1-->3)-alpha-D-Gal-(1-->4)-beta-D-Gal-(1-->4)-D-Glc] and the terminal
      trisaccharide, as well as the methyl alpha-glycoside 1 of the terminal
      disaccharide, were synthesised by silver trifluoromethanesulfonate-promoted beta
      glycosylation of suitably protected galactoside, galabioside, and globotrioside
      alcohols with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-galactopyranosyl
      chloride, followed by removal of protecting groups. Removal of the anomeric TMSEt
      group of the globotetraoside and of the terminal trisaccharide, using
      trifluoroacetic acid-dichloromethane, gave the corresponding hemiacetal sugars 8
      and 3. The TMSEt glycoside of the terminal trisaccharide was converted, via the 1
      acetate, into the corresponding isobutyl (4) and 3-butylsulfonyl-2
      [(butylsulfonyl)methyl]propyl (5) glycosides and into the TMSEt thioglycoside 6
      via the glycosyl bromide.

PMID- 8137357
TI  - Synthesis of the Forssman pentasaccharide and terminal tetra-, tri-, and di
      saccharide fragments.
AB  - The 2-(trimethylsilyl)ethyl (TMSEt) beta-glycosides of the Forssman
      pentasaccharide [alpha-D-GalNAc-(1-->3)-beta-D-GalNAc-(1-->3)-alpha-D-Gal- (1-
      >4)-beta-D-Gal-(1-->4)-D-Glc] and the terminal tetrasaccharide, as well as the
      methyl glycosides 1 and 2 of the terminal di- and tri-saccharides, were
      synthesised by silver trifluoromethanesulfonate-promoted alpha-glycosylation of
      suitably protected mono-, di-, tri-, and tetrasaccharide alcohols with 3,4,6-tri
      O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl bromide, followed by removal of
      protecting groups. The anomeric TMSEt group of the Forssman pentasaccharide and
      terminal tetrasaccharide was removed with trifluoroacetic acid-dichloromethane,
      to give the corresponding hemiacetal sugars 4 and 6.

PMID- 8137358
TI  - Synthesis of di- and tri-saccharides with intramolecular NH-glycosidic linkages:
      molecules with flexible and rigid glycosidic bonds for conformational studies.
AB  - Attempted dephthalimidation of the trisaccharide 1-O-acetyl-3,4-di-O-benzyl- 2,6
      di-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl )-alpha-D
      mannopyranose (1) and its derivatives 2 and 3, as well as the disaccharide 1-O
      acetyl-3,4,6-tri-O-benzyl-2-O-(3,4,6-tri-O-acetyl- 2-deoxy-2-phthalimido-beta-D
      glucopyranosyl)-alpha-D-mannopyranose (13), with hydrazine hydrate in ethanol at
      80 degrees C, produced the trisaccharide-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2
      deoxy-beta-D- glucopyranosyl)-3,4-di-O-benzyl-beta-D-mannopyranose-3',4',6'-tri-O
      a cet yl- beta-D-glucopyranose 1,2'-N:1',2-O-dianhydride (4) and 3,4,6-tri-O
      benzyl-beta-D-mannopyranose 3',4',6'-tri-O-acetyl-beta-D-glucopyranose 1,2'
      N:1',2-O-dianhydride (14), respectively, containing an intramolecular NH
      glycosidic linkage. The conventional deblocking of compounds 4 and 14 gave the
      completely deblocked trisaccharide 6-O-(2-acetamido-2-deoxy-beta-D
      glucopyranosyl)-beta-D-mannopyranose beta-D-glucopyranose 1,2'-N:1',2-O
      dianhydride (6) and the disaccharide beta-D-mannopyranose beta-D-glucopyranose
      1,2'-N:1',2-O-dianhydride (16), respectively, containing an intact intramolecular
      NH-glycosidic bond. The unusual intra NH-glycosyl character makes the linkage
      rigid, and therefore these compounds should not only be useful for NMR studies
      but also as substrates or inhibitors of GlcNAc-transferases.

PMID- 8137359
TI  - Carrageenan from the tetrasporic stage of Gigartina decipiens (Gigartinaceae,
      Rhodophyta).
AB  - The structure of the polysaccharide isolated from tetrasporophytic plants of the
      New Zealand red alga Gigartina decipiens has been determined by chemical and
      spectroscopic techniques. It is a linear polymer composed primarily of
      alternating 3-linked beta-D-galactopyranosyl 2-sulphate and 4-linked alpha-D
      galactopyranosyl 2,6-disulphate residues. About 15% of the 3-linked residues have
      an additional sulphate ester group at the 6-position. Aside from this small extra
      sulphate substitution, the structure is that of the idealised lambda-carrageenan.
      Good quality solution-state 13C NMR spectra were recorded and interpreted for
      this carrageenan and for the carrageenans produced from it by solvolytic
      desulphation and alkali modification.

PMID- 8137360
TI  - Structural roles of calcium ions and side chains in welan: an X-ray study.
AB  - Welan is the first branched polymer in the gellan family of polysaccharides whose
      three-dimensional structure has been determined by X-ray diffraction analysis of
      polycrystalline and well oriented fibers of the calcium salt. The molecule exists
      as a half-staggered, parallel, double-helix, similar to that of gellan. The side
      chains fold back on the main chain to form hydrogen bonds with the carboxylate
      groups. This shielding enhances the stability of the double-helix. Three
      molecules are organized in a trigonal unit cell of dimensions a = 20.83 and c =
      28.69 A with a lateral separation of 12.0 A in each pair; this is 2.9 A larger
      than in gellan. The double helices are in contact with each other through calcium
      ions and water molecules via COO-...Ca2+...COO- and COO-...W...Ca2+...COO-
      interactions, and through side chain-side chain hydrogen bonds. These structural
      features enable us not only to explain how the side chains in welan are
      responsible for the enhanced molecular stability relative to gellan, but also to
      show how essential they are for the associative properties which control the
      rheology of the polymer.

PMID- 8137361
TI  - Native ordered structure of welan polysaccharide: conformational transitions and
      gel formation in aqueous dimethyl sulphoxide.
AB  - Welan, in aqueous solution, has "weak gel" properties analogous to those of
      ordered xanthan but, unlike xanthan, shows no evidence of conformational change
      between 0 and 100 degrees C. When the polymer is dissolved in dimethyl sulphoxide
      (Me2SO) rather than in water, however, there is a massive decrease in viscosity
      and total loss of gel-like character. In mixtures of the two solvents, the change
      in rheology occurs over a narrow range of composition (approximately 85-90% v/v
      Me2SO for 0.5% welan). On heating and cooling in a solvent close to the lower end
      of the critical range (86% Me2SO), the polymer shows typical order-disorder and
      disorder-order transitions [as monitored by optical rotation, differential
      scanning calorimetry, and temperature-course of rheological change]. When
      solutions of disordered welan in Me2SO are poured into excess water they form
      cohesive strings of gel. We interpret these results as showing that: (1) the
      stable conformation of welan in water is the double helix structure identified by
      X-ray fibre diffraction in the solid state; (2) in native welan, as
      biosynthesised, the strands are perfectly paired, and ordered along their full
      length; (3) on exposure to high concentrations of Me2SO, the native structure is
      dissociated into disordered coils; (4) rapid renaturation from the disordered
      state gives shorter helices, with exchange of partners to form a stable cross
      linked network.

PMID- 8137362
TI  - Structural elucidation of the specific capsular polysaccharide of Rhodococcus
      equi serotype 7.
AB  - Structural analysis of the specific capsular polysaccharide produced by
      Rhodococcus equi serotype 7 indicated it to be a high-molecular-weight polymer
      consisting of equal molar amounts of D-galactose, D-mannose, L-rhamnose, and
      pyruvic acid. By employing a combination of chemical and NMR techniques, it was
      established that the polysaccharide is composed of the linear repeating
      trisaccharide units: [formula: see text] -->3)-alpha-D-Galp-(1-->3)-alpha-D-Manp
      (1-->3)-alpha-L-Rhap -(1-->, in which the cyclic pyruvic acid acetal groups
      bridging the O-4 and O-6 positions of the alpha-D-Manp residues have the S
      configuration. The 1H and 13C NMR spectra of the native and pyruvic acetal-free
      polysaccharides were fully assigned.

PMID- 8137363
TI  - Isolation and structural characterization of beta-D-glucosyluronic acid and 4-O
      methyl beta-D-glucosyluronic acid-containing oligosaccharides from the cell-wall
      pectic polysaccharide, rhamnogalacturonan I.
AB  - Rhamnogalacturonan I (RG-I), a pectic polysaccharide isolated from the walls of
      suspension-cultured sycamore cells, was shown by glycosyl-residue composition
      analysis to contain D-glucosyluronic acid (GlcpA) residues (1 mol%) and 4-O
      methyl-D-glucosyluronic acid (4-O-Me-GlcpA) residues (0.5 mol%). These
      monosaccharides were shown, by glycosyl-linkage analysis, to be present in RG-I
      as terminal nonreducing residues. The glycosyl sequences containing GlcpA and 4-O
      Me-GlcpA were determined by structurally characterizing the acidic
      oligosaccharides released by partial acid hydrolysis of RG-I. Six acidic
      oligosaccharides were purified by semipreparative high-performance anion-exchange
      chromatography with pulsed amperometric detection (HPAEC-PAD) and characterized
      by glycosyl-residue and glycosyl-linkage composition analyses, GLC-CIMS, GLC
      EIMS, electrospray MS (ESMS), and 1H NMR spectroscopy. We propose that three of
      the acidic oligosaccharides characterized, 4-O-Me-beta-D-GlcpA-(1-->6)-D-Gal,
      beta-D-GlcpA-(1-->6)-D-Gal, and beta-D-GlcpA-(1-->4)-D-Gal, originate from the
      galactosyl-containing side chains of RG-I. The three other acidic
      oligosaccharides characterized, alpha-D-GalpA-(1-->2)-L-Rha, alpha-D-GalpA-(1-
      >2)-alpha-L-Rhap-(1-->4)-alpha-D-GalpA+ ++-(1-->2)-alpha-L-Rha, and alpha-D-GalpA
      (1-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GalpA+ ++-(1-->2)-alpha-L- Rhap-(1-->4)
      alpha-D-GalpA-(1-->2)-alpha-L-Rha, were generated by partial hydrolysis of the RG
      I backbone. No evidence was obtained for the presence of galactosyluronic acid in
      the side chains of RG-I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137364
TI  - X-ray structure of methyl 1,6-di-O-(4-bromobenzoyl)-3,4-di-O-(4-methoxycinnamoyl)
      beta-D-fructofu ranoside .

PMID- 8137365
TI  - A facile total synthesis of ganglioside GD2.

PMID- 8137366
TI  - A convenient laboratory procedure for the preparation of cortalcerone, a fungal
      antibiotic beta-pyrone.

PMID- 8137367
TI  - L-dianose, a new monosaccharide from Dianthus chinensis L.

PMID- 8137368
TI  - Structure of the capsular polysaccharide and the O-side-chain of the
      lipopolysaccharide from Acetobacter methanolicus MB 58 (IMET B346).

PMID- 8137369
TI  - Structural and molecular properties of the arabinogalactan isolated from
      Mongolian larchwood (Larix dahurica L.).

PMID- 8137370
TI  - Differing rates of galactosylation of homologous spacer-modified disaccharides
      are an indication for two separate GlcNAc binding-sites in galactosyltransferase.

PMID- 8137371
TI  - Effect of heat-moisture treatment on the structure and physicochemical properties
      of cereal, legume, and tuber starches.
AB  - Native wheat, oat, lentil, yam, and potato starches were heat treated at 100
      degrees C for 16 h at moisture contents between 10 and 30%. The heat treatment
      did not change granule size and shape. In oat starch, granules were less
      compactly packed after heat treatment. The X-ray diffraction intensities
      increased in wheat, oat, and lentil starches, but decreased in potato and yam.
      The X-ray patterns of wheat and oat starches remained unchanged, while those of
      lentil, potato, and yam starches became more cereal-like. In all starches, the
      swelling factor and amylose leaching decreased, being more pronounced in potato.
      Heat treatment induced complex formation between amylose and native lipids.
      Differential scanning calorimetry of the heat-treated samples showed a broadening
      of the gelatinization-temperature range and a shifting of the endothermal
      transition towards higher temperatures. These changes were more pronounced in
      potato starch. The gelatinization enthalpy of wheat, oat, and lentil starches
      remained unchanged, but those of potato and yam starches decreased on heat
      treatment. Heat treatment increased the 95 degrees C viscosity of wheat starch,
      but decreased those of oat lentil, potato, and yam starches. In all starches,
      thermal and shear stability increased after heat treatment. Acid hydrolysis
      decreased on heat treatment of wheat and lentil starches, but increased in oat,
      potato, and yam starches. However, in potato and yam starches, the foregoing
      trend was evident only during the first seven days of hydrolysis. Thereafter,
      acid hydrolysis was more pronounced in native than in heat-treated starches. The
      susceptibility towards hydrolysis by porcine pancreatic alpha amylase decreased
      on heat treatment of wheat and lentil starches, whereas increases were observed
      for oat, potato, and yam starches. The results indicated that the extent of
      starch-chain associations within the amorphous regions and the degree of
      crystalline order are altered during heat-moisture treatment. The magnitude of
      these changes were found to be dependent upon the moisture content during heat
      treatment and on the starch source.

PMID- 8137372
TI  - Chemical synthesis and NMR spectra of a protected branched-tetrasaccharide
      thioglycoside, a useful intermediate for the synthesis of branched
      oligosaccharides.
AB  - Acid-catalyzed thiophenolysis of per-O-acetylated 1,6-anhydromaltose (3) gave
      phenyl 2,3-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-alpha-D- glucopyranosyl)-1
      thio-beta-D-glucopyranoside (4) in quantitative yield. Phenyl 4-O-alpha-D
      glucopyranosyl-1-thio-beta-D-glucopyranoside (5) was obtained by acid-catalyzed
      thiophenolysis of maltose octaacetate (2), using trimethylsilyl triflate as
      catalyst, and subsequent deacetylation. Standard benzylation of 5 gave phenyl 2,3
      di-O-benzyl-4-O- (2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl)-1-thio-beta-D
      glucopy ran oside (6) which upon treatment with N-bromosuccinimide in aqueous
      acetone gave 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-alpha-D-
      glucopyranosyl)-D-glucopyranose (8). Compound 8 was treated with
      trichloroacetonitrile in the presence of anhydrous potassium carbonate to give
      2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl- alpha-D-glucopyranosyl) 
      alpha,beta-D-glucopyranosyl trichloroacetimidate (9), which was effectively used
      as the glycosyl donor in the condensation reaction with compound 4, using
      trimethylsilyl triflate as catalyst, to obtain the branched tetrasaccharides
      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-be ta-D- glucopyranoside (10) and
      phenyl O-[(2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl)-(1-->4)]- O-(2,3,4-tri
      O-benzyl-beta-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-glucopy ran oside (11) in
      67 and 21% yield, respectively. A complete NMR interpretation of 10 is presented.
      Alternative methodologies for the synthesis of the branched tetrasaccharides were
      investigated. Chemical synthesis of the phenyl thioglycoside 5 was achieved by
      deacetylation of 4. Reaction of 6 with diethylaminosulfur trifluoride in the
      presence of N-bromosuccinimide gave 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O
      benzyl-alpha-D- glucopyranosyl)-alpha,beta-D-glucopyranosyl fluoride (7) in 78%
      yield. Subsequent condensation of 7 and 4, using the combination silver
      perchlorate-stannous chloride as catalyst, gave the corresponding branched
      tetrasaccharides 10 and 11 in 55 and 10% yield, respectively.

PMID- 8137373
TI  - Elders' expected and realized benefits from cardiac surgery.

PMID- 8137374
TI  - [Perinatal drug administration and risks of functional teratogenic defects].
AB  - The success of perinatal medicine in saving the risk pregnancies and the lives of
      very immature and injured newborns is connected with a growing use of drugs which
      may disturb perinatal ontogenetic processes characterized by intensive
      histogenesis and cytodifferentiation of already formed organs, predominantly the
      brain. The administered drugs can change the program of the formation of neural
      nets, synapses, receptors and neurotransmitters and induce permanent deviations
      of brain cytoarchitectonics and neurobiochemical equipment. This pathology is not
      evident at birth, but forms the basis for functional defects of the brain which
      become apparent gradually during maturation or even in adulthood as neuro
      psychological deviations e.g. minimal brain dysfunction or mental retardation in
      school children, sensori-motor deficits, epilepsy, psychic lability and
      maladjustment which may represent a predisposition to psychoses. Clinical
      recognition of this functional teratogenic action of the drug is hampered by the
      long time interval (upto decades) between the drug administration and its
      consequences what makes the identification of causal relations very difficult.
      Consequently, experimental research is necessary concerning functional
      teratogenicity of all drugs given in perinatal period, however under the
      precondition of adequate animal models with sufficient validity for the
      extrapolation on human level. The synopsis of current knowledge in this field
      reveals great numbers of urgent problems which are to be studied.

PMID- 8137375
TI  - [Comparison of the effects of 2 preparations of cyclosporin A-- Consupren and
      Sandimmune--from the aspect of functional and morphologic changes in rats with
      renal ischemia].
AB  - BACKGROUND: Cyclosporine A is in transplantology an irreplaceable
      immunosuppressive agent. Its only manufacturer preparation Sandimmune--was the
      Swiss firm Sandoz. In 1990 the Czech firm Galena introduced cyclosporine A with
      the name Consupren on the market. The objective of the present investigation was
      to assess whether the nephrotoxic effect of the two preparations is comparable,
      or whether it differs. METHODS AND RESULTS: In a group of 65 rats after
      unilateral nephrectomy and 45-minute ischaemia of the remaining kidney the
      nephrotoxic action of cyclosporine preparations Sandimmune (Sandoz) and Consupren
      (Galena, CZ) administered in doses of 10 mg/kg body weight/24 hours throughout
      the experiment was investigated. The functional and morphological examination was
      made 3 or 21 days following nephrectomy. After three days the serum levels of
      creatinine, urea, sodium, osmolality and their urinary excretion as well as the
      intensity of proteinuria and morphological findings using light and electron
      microscopy did not differ in the two groups. The same was found during follow-up
      after 21 days; the small difference in the serum creatinine level only
      (Sandimmune 96.0 +/- 9.7 mumol/l, Consupren 111.4 +/- 11.2 mumol/l; p < 0.005)
      may be associated with the significantly higher cyclosporin levels following
      Consupren administration. CONCLUSIONS: The findings of the investigation support
      the idea that even after ischaemic kidney damage the nephrotoxicity of Consupren
      is not higher than that of Sandimmune.

PMID- 8137376
TI  - [Therapy in kidney transplant rejection using murine monoclonal IgG2a A1CD3
      (Cedetrin)].
AB  - BACKGROUND: One of the substances used in recent years to suppress immune
      reactions after organ and tissue transplantations is mouse IgG2a globulin which
      acts selectively on CD3 lymphocytes; it is known under the name of Orthoclone
      (Ortho Co.) An analogous preparation was developed in the Institute of Molecular
      Genetics, Academy of Sciences, Czech Republic, although the idiotype is
      different. The authors submit a report on the experience with treatment of
      rejection of transplanted kidneys. METHODS RESULTS: Monoclonal mouse globulin
      IgG2a (Cedetrin) was administered to 20 patients after renal transplantation on
      account of a rejection episode or progressing rejection; the mean interval after
      transplantation was 16.1 (range 0.25-96) months; the rejection episode or
      progressing rejection responded little in the majority of patients to 6-alpha
      methyl prednisolone (Urbason, Hoechst, Solu-Medrol, Upjohn). For prophylactic
      immunosuppression the following combinations were used: cyclosporin +
      azathioprine + prednisone (17x) or azathioprine + prednisone (3x). Cedetrin was
      administered by the i.v. route in two to 11 doses a 3 mg substance. Of 20
      patients in 6 Cedetrin administration had to be discontinued (allergy, infection,
      leucopenia, hyperhydration). In 14 the tolerance was satisfactory, the type and
      frequency of side-effects was similar as after Orthoclone; the antibody formation
      was less frequent. The specificity of Cedetrin as regards its action on T
      lymphocytes was confirmed. The effect was good to very good in 6 of 8 patients
      where the rejection filtrate was histologically active. In 9 patients treated
      during the first year after renal transplantation the cumulative survival of the
      graft at the end of the 12th, 24th and 36th month following transplantation was
      89%, 67% and 56% resp. Because the therapeutic effect depended on histologically
      proved rejection activity, the authors consider biopsy of the graft before
      Cedetrin treatment essential. CONCLUSIONS: The therapeutic administration of
      monoclonal mouse globulin IgG2a A1CD3 (Cedetrin), developed in the Institute of
      Molecular Genetics, Academy of Sciences, Czech Republic, produced by Exbio Co.,
      CR) has a favourable effect on rejection episodes or progressing rejection of
      transplanted kidneys. Treatment is indicated in confirmed histologically active
      rejection.

PMID- 8137377
TI  - [Monitoring lymphocyte activity in the peripheral blood of patients after bone
      marrow transplantation].
AB  - BACKGROUND: After bone marrow transplantation serious complications develop which
      may limit the success of this therapeutic method. One of the early complications
      is an acute graft versus host reaction. The objective of the investigation was to
      evaluate the relationship between the number of active lymphocytes in the
      patient's blood stream after bone marrow transplantation and the development of
      an acute graft versus host reaction or rejection of the graft, and thus
      contribute towards prediction or diagnosis of these complications. METHODS AND
      RESULTS: In 14 patients with acute myeloid leukaemia (3), acute lymphatic
      leukaemia (1), chronic myeloid leukaemia (6), myelodysplastic syndrome (2) and
      aplastic anaemia (2) bone marrow was transplanted: the donor was in all instances
      a HLA identical sibling. However, only 11 patients were evaluated. In the latter
      changes in the number of circulating active lymphocytes were assessed: their
      activity was evaluated from nucleolar characteristics expressed by RNA synthesis.
      Their values at the time of the acute graft versus host reaction (GVHD) varied
      between 7.4% and 17.3%; at the time when these patients were free from
      complications they were 2.2%-6.0% (the difference is at the borderline of
      significance). In 8 patients the rise of active lymphocytes preceded the
      manifestation of the graft versus host reaction by 3-7 days. At the time of
      infectious complications after bone marrow transplantation (temperatures of
      obscure origin, herpetic infections, varicella, adenoviral infections) the number
      of active lymphocytes did not increase (2.0%-10.0%), as compared with 3.4%-9.5%
      in the group without complications. CONCLUSIONS: The increased percentage of
      activated lymphocytes in the peripheral blood stream of patients with an acute
      graft versus host reaction (GVHD) after bone marrow transplantation results from
      specific immunological procedures. Their assessment could help with the
      differential diagnostic difficulties frequently associated with the diagnosis of
      the acute graft versus host reaction.

PMID- 8137378
TI  - [Acute anicteric hepatitis and intrahepatic cholestasis caused by administration
      of prajmalium bitartrate (Neo-Gilurytmal)].
AB  - The authors draw attention to a serious drug response to the derivative of the
      alkaloid ajmaline prajmalium (Neo-Gilurytmal, Giulini-GFR) which causes
      impairment of liver functions of various grades as a result of intrahepatic
      cholestasis. They draw attention to the necessity of a careful pharmacological
      case-history, evaluation of the premorbid stage, in particular former liver
      disease or contemporary administration of drugs which burden liver function
      (hormonal contraceptives, non-steroid antirheumatic drugs). It is essential to
      follow-up liver functions by laboratory tests already at the onset of treatment
      with Neo-Gilurytmal.

PMID- 8137379
TI  - [Basic ethics in intensive care].

PMID- 8137380
TI  - [Thoughts on 40 years devoted to preservation of biological materials].

PMID- 8137381
TI  - [Extraterrestrial influences on health and disease].
AB  - As to extraterrestrial influences on man in health and disease so far only the
      effect of the sun and moon are known. This concerns the effect of solar radiation
      of different wavelengths and the effect of corpuscular solar radiation which has
      an impact on the condition of the terrestrial magnetic field and electric
      conditions in the atmosphere. Moreover there is also a question of important
      influences of gravitation (tides). Here the influence of the position of the moon
      in relation to the connecting line between sun and earth is involved. In the
      course of the synodic month (from new moon to the next new moon) a semilunar
      periodicity of different medical and geomagnetic indicators as well as
      meteorological ones plays a part. Based on his own research and that of others
      the author reaches the conclusion that extraterrestrial and terrestrial
      influences are interrelated and exert a mutual influence on each other and that
      it is not sensible to separate them strictly. Investigation of all the mentioned
      influences is important not only for biomedical prognosis but also for basic
      geophysical and meteorological research. Perspectively it would be useful to plan
      model experiments. The author feels it is his duty to refuse publication of
      different horoscopes in the mass media, whatever the intention. In the lay public
      this may lead to popularization of astrology which has nothing in common with
      serious research.

PMID- 8137382
TI  - [Renal resistance to atrial natriuretic factor as a cause of the escape failure
      phenomenon in patients with non-ascitic liver cirrhosis].
AB  - BACKGROUND: Chronic administration of synthetic mineralocorticoids leads in
      healthy subjects only to temporary fluid retention with subsequent restoration of
      sodium balance, i.e. the so-called mineralocorticoid escape phenomenon. There is
      a failure of mineralocorticoid escape in patients with ascitic liver cirrhosis
      with progressive fluid retention. The aim of this study was to contribute to the
      elucidation of the mechanisms of the escape phenomenon in patients with
      preascitic liver cirrhosis. METHODS AND RESULTS: Synthetic mineralocorticoid,
      fludrocortisone, was administered for 7 days to 8 patients with non-ascitic liver
      cirrhosis (LC) and 6 controls (CO) on a high sodium diet. CI seemed to have some
      central volume expansion before fludrocortisone administration, as assessed from
      a higher left atrial diameter and lower plasma aldosterone. Fludrocortisone
      administration in CI led to a comparable increase of ANF and suppression of
      plasma aldosterone as in CO with a higher diameter of the left atrium and lower
      PRA than in controls. Despite a comparable increase of ANF after fludrocortisone
      administration cGMP excretion was significantly higher in CO than in CI (434.5 +
      247.1 vs. 824.6 + 317.3 pmol/min, p < 0.05). Natriuresis of CI seemed to depend
      on urinary cGMP excretion before fludrocortisone administration. The natriuretic
      response of these CI to a high sodium diet was exaggerated (290.0 + 53.9 vs.
      160.0 + 18.3, p < 0.05), but they were unable to escape completely from the
      retaining effect of fludrocortisone. CONCLUSIONS: Failure of mineralocorticoid
      escape in patients with preascitic liver cirrhosis may be due to the renal
      resistance to ANF with insufficient increase of urinary cGMP excretion.

PMID- 8137383
TI  - [Evaluation of physical activity in obese individuals].
AB  - BACKGROUND: Dynamic exercise is the optimal form of spending leisure time and
      forms the contents of the majority of children's games. It is a risk to restrict
      (or enforce) physical activity in particular on young children. This pertains
      also to obese children where the regulation of the ratio energy input: energy
      output is one of the therapeutic components. METHODS AND RESULTS: The authors
      investigated physical activity during spontaneous activity in a group of 36 obese
      subjects, 20 non-obese controls and 41 comparable subjects aged 8-16 years (with
      the exception of a group of 13-14-years-olds the obese children were taller than
      the control group). Assessment by concealed camera. Children had a varied
      selection of gymnastic apparatuses and other activities. Concurrently the heart
      rate was recorded (by a Sport-Tester Pollar, evaluated by Sony equipment).
      Everything was rated as active movement with the exception of the standing,
      sitting or recumbent position. The examiners did not interfere with the physical
      activity. The assembled values confirm the basic need of activity in relation to
      age and the important role of elevated body weight. The latter was the reason
      why, while less time was spent for exercise (chronometer), the heart rate of
      obese subjects did not differ significantly from that of the control group during
      spontaneous physical activity and during a 3-minute run. CONCLUSIONS: Controlled
      physical activity must always respect the total burdening with excessive body
      weight as well as the physical action of overweight. Physical activity of young
      subjects with a higher body weight is in relation to needs of exercise of the
      given age group and to their total body weight.

PMID- 8137384
TI  - [Who will decide if further treatment is futile?].

PMID- 8137385
TI  - [The medal and coin collection at the Museum of Medicine in Prague].

PMID- 8137386
TI  - [Biological markers in depression].
AB  - Identification of biological markers in mental diseases could partly resolve
      problems associated with their diagnosis, treatment, prognosis and prevention. At
      present biochemical markers of depression seem to be most promising. Development
      of research in this area was created by the use of platelets as a readily
      accessible neurone model and by application of neuroendocrinological dynamic
      tests. Most ample experience has been assembled so far with the application of
      the so-called dexamethasone suppression test. The impact of biochemical markers
      in a disease so frequent and so serious as depression should arouse greater
      interest of psychiatrists in this so far somewhat omitted area.

PMID- 8137387
TI  - [Ethical problems in health care].
AB  - Changes in the scale of values associated with society entering plural democracy
      caused as regards conceptual problems of health care some ethical doubts and
      objections. In the author's opinion the most important ones are: problems on the
      essence of health and mission of health policy, responsibility for health care,
      nature of health services under conditions of market economy, problems of the
      interpretation of right to health, health requirements and the importance of
      equity in advanced cultural societies.

PMID- 8137388
TI  - [New findings on endogenous drug receptor ligands].
AB  - Since the discovery of endogenous ligands for opiate receptors, endorphins and
      enkephalins some 30 years have elapsed. The fact that one of the breakdown
      products of the common precursor (proopiomelanocortin, POMC) ACTH and opioid
      peptides, i.e. ACTH 1-24 has a saluretic effect (balancing perhaps sodium
      retention after activation of the adrenal cortex) was not generally accepted yet
      although MSH as well as some fragments of the ACTH molecule have a natriuretic
      effect. The endogenous digitalis-like immunoreactive factor, DLF (even ACTH
      displays some DLF activities) which inhibits NaK-ATPase originates from the
      adrenals and is probably identical with ouabain, although I have doubts on
      conclusive evidence. The physiological function of DLF is not known either.
      Endogenous benzodiazepines ("endozepins") probably play a part in the modulation
      of cerebral activity: their excess may be associated with a nosological entity,
      idiopathic recurrent stupor. Nitric oxide, a mediator of vasorelaxing reactions,
      caused by acetylcholine, has already penetrated into general clinical thinking.
      There are at least ten diseases where NO plays a part. It is not only an
      endogenous factor which imitates more perfectly the action of organic nitrates
      but also a nervous mediator and it shares this function with another gaseous mini
      hormone, carbon monoxide (CO). Endogenous ligands of drug receptors comprise also
      endogenous substances which interreact with receptors for calcium inhibitors
      (inhibitors of calcium channels). Here are important clinical perspectives not
      only in cardiology. There are moreover endogenous ligands for receptors for
      marihuana (tetrahydrocannabinols) in particular a derivative of arachidonic acid
      anandamide (substance of "inner bliss").(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137389
TI  - [Antioxidant enzyme activity in the gastric mucosa in precancerous conditions].
AB  - BACKGROUND: The primary defense against oxidation damage of tissues are anti
      oxidant enzymes, e.g. superoxide dismutase, catalase and glutathione peroxidase.
      Some non-enzymatic substances have a significant anti-oxidant action (e.g.
      vitamin C, E, beta-carotene and others). The objective of the present work was to
      follow up the Cu/Zn superoxide dismutase activity, catalase and glutathione
      peroxidase (anti-oxidant enzymes of the gastric mucosa) in subjects with the risk
      of developing gastric cancer, e.g. those suffering from atrophic gastritis,
      hyperplastic polyps and gastric adenoma. METHODS AND RESULTS: The authors
      examined 80 subjects (50 men and 30 women) aged 25 - 71 years. In all during
      endoscopic examination bioptic specimens of the mucosa were taken at standard
      sites of the gastric corpus and antrum for histological and enzymological
      examination. Enzymological examination: activity of Cu/Zn-superoxide dismutase
      (Randox Lab. Ltd. GB kit), catalase activity (modified method of Cavarocchia et
      al.) and glutathione peroxidase activity (method according to Paglia and
      Valentine). The Cu/Zn-superoxide dismutase activity was elevated in the group of
      patients with gastritis after gastrectomy (67%) and with gastric adenoma (35%),
      the catalase activity in patients with gastritis after gastrectomy (40%) and the
      glutathione peroxidase activity in patients with the diagnosis of gastritis after
      gastrectomy (185%), atrophic gastritis (46%) hyperplastic polyp (50%) and gastric
      adenoma (50%). CONCLUSIONS: The increased activity of anti-oxidant enzymes was
      due to a higher concentration of the superoxide anion radical, hydrogen peroxide
      and organic peroxides (lipoperoxides); the source of active types of oxygen are
      phagocytic leucocytes in the chronically inflamed gastric mucosa.

PMID- 8137390
TI  - [Transparietal puncture aspiration biopsy of the lung and mediastinum].
AB  - BACKGROUND: The contribution of fine needle transparietal aspiration biopsy for
      the diagnosis of diseases of thoracic organs is generally accepted. The objective
      of the present study is to evaluate the contribution of this method to the
      diagnosis of processes in the lung and mediastinum. METHODS AND RESULTS:
      Transparietal fine needle aspiration biopsy was performed in 115 patients, 75 men
      and 40 women, mean age 59 +/- 10.7 years in men and 58.4 +/- 10.3 years in women.
      The site of insertion and position of the needle were checked by skiascopy. The
      assembled material was evaluated cytologically under a light microscope.
      Malignant tumours were classified according to WHO recommendations. The greatest
      diagnostic yield of the method was in a group of 73 patients with clinical
      suspicion of a malignant process; this suspicion was confirmed by cytological
      examination in 50 patients, i.e. in 68.5% of the patients. In 7 of 15 patients
      with suspected tuberculosis cytological evidence of epithelioid and Langerhans
      cells supported the diagnosis of pulmonary tuberculosis; from four punctures of
      mediastinal formations confirmed a malignant tumour in half of them. In a
      relatively large group of patients with inflammatory processes the cytological
      finding did not prove useful for establishment of the diagnosis. Complications of
      this examination in the whole group were recorded in 18 patients (15.6%). The
      most frequent complication was the development of pneumothorax (18 patients,
      15.6%) which however, only in 2 patients required exsufflation. In three patients
      after the procedure minimal haemoptysis developed. CONCLUSIONS: Complications,
      although fairly frequent (15.6%), are not serious.

PMID- 8137391
TI  - [Transjugular renal biopsy--initial experience].
AB  - BACKGROUND: Transjugular renal biopsy (TJRB) is a new method designed to obtain
      bioptic specimens of the kidney. It has defined indications in situations where
      application of the standard percutaneous technique involves an increased risk. It
      is used in particular in cases with impaired haemocoagulation with a different
      aetiology. The method was not used so far in this country. The authors describe
      the initial experience with TJRB. METHODS AND RESULTS: After cannulation of the
      right internal jugular vein under continuous skiascopic control a catheter was
      inserted into the right renal vein. Through the lumen of the catheter a special
      bioptic needle is inserted. The collection proper of renal tissue is made by the
      puncture- aspiration technique. The authors performed TJRB in 10 patients, in 8
      specimens of the renal cortex were collected, on average seven glomeruli. The
      histological examination was a significant contribution to diagnosis in seven
      patients. The development of subcapsular haematoma with a clinical symptomatology
      was recorded in three patients, other complications were not observed.
      CONCLUSIONS: TJRB is a new diagnostic method, which with regard to its
      indications, no doubt, facilitates the diagnosis of glomerulopathies. Although
      the method is demanding from the technical aspect, if done correctly, it involves
      little risk. It is well tolerated and reduced the risk of possible complications
      of renal biopsy.

PMID- 8137392
TI  - [70 years of the History of Medicine Institute at the First Medical College of
      Charles University in Prague].

PMID- 8137394
TI  - Early postnatal growth of skeletal muscle blood vessels of the rat.
AB  - The development of blood vessels during the first three postnatal weeks was
      studied in the ventral stripe of the spinotrapezius muscle of the rat by use of
      India ink-gelatine injections, and electron microscopy. The number of terminal
      arterioles and collecting venules remained unchanged postnatally in the observed
      area. A remarkable proximodistal gradient of vascular development was apparent:
      while the basic structure of the hilar vessels remained unchanged in the time
      studied, the intramuscular arteries and veins matured gradually. More
      peripherally, gradual maturation of terminal and precapillary arterioles was
      observed. The capillary endothelium and the pericytes showed immature features,
      and remained unchanged during the time studied. An intense rebuilding activity
      was found in the endothelial cells of the growing venules, expressed by various
      forms of gaps, covered by an intact basal lamina and pericytes. Numerous mast
      cells and macrophages were found along all vessels. Intramuscular lymphatics were
      not present prior to the first postnatal week.

PMID- 8137393
TI  - Subcellular distribution of tissue kallikrein and Na,K-ATPase alpha-subunit in
      rat parotid striated duct cells.
AB  - Intracellular protein distribution and sorting were examined in rat parotid
      striated duct cells, in which tissue kallikrein is apical, and Na,K-ATPase is
      basolateral. Electron-microscopic immunogold cytochemistry, with both polyclonal
      and monoclonal antibodies, demonstrated these enzymes at opposite poles of the
      cells and in distinct intracellular sites. Kallikrein was found within apical
      secretory granules, whereas Na,K-ATPase was present on basolateral cell
      membranes. In addition, kallikrein was localized throughout cisternae of all
      Golgi profiles, whereas Na,K-ATPase (alpha-subunit) was found only in small
      peripheral vesicles and/or lateral cisternal extensions of a basal subset of
      Golgi profiles. These differences in the subcellular distribution of the two
      marker antigens were most clearly seen with double immunogold labelling. Our
      results suggest that kallikrein, an apical, regulated secretory protein, and Na,K
      ATPase, a basolateral, constitutively transported membrane protein, are
      segregated at (or prior to) the level of the Golgi apparatus rather than in the
      trans-Golgi network (TGN), as was expected.

PMID- 8137396
TI  - Molecular structure and functional morphology of echinoderm collagen fibrils.
AB  - The collagenous tissues of echinoderms, which have the unique capacity to rapidly
      and reversibly alter their mechanical properties, resemble the collagenous
      tissues of other phyla in consisting of collagen fibrils in a nonfibrillar
      matrix. Knowledge of the composition and structure of their collagen fibrils and
      interfibrillar matrix is thus important for an understanding of the physiology of
      these tissues. In this report it is shown that the collagen molecules from the
      fibrils of the spine ligament of a sea-urchin and the deep dermis of a sea
      cucumber are the same length as those from vertebrate fibrils and that they
      assemble into fibrils with the same repeat period and gap/overlap ratio as do
      those of vertebrate fibrils. The distributions of charged residues in echinoderm
      and vertebrate molecules are somewhat different, giving rise to segment-long
      spacing crystallites and fibrils with different banding patterns. Compared to the
      vertebrate pattern, the banding pattern of echinoderm fibrils is characterized by
      greatly increased stain intensity in the c3 band and greatly reduced stain
      intensity in the a3 and b2 bands. The fibrils are spindle-shaped, possessing no
      constant-diameter region throughout their length. The shape of the fibrils is
      mechanically advantageous for their reinforcing role in a discontinuous fiber
      composite material.

PMID- 8137395
TI  - Differential expression of alpha, mu, and pi classes of glutathione S
      transferases in chemosensory mucosae of rats during development.
AB  - The expression of three classes of glutathione S-transferases (GSTs), Alpha, Mu,
      and Pi was investigated in the nasal mucosae of rats during development using
      immunohistochemical methods. GST Alpha and Mu were first detected in the
      supranuclear region of sustentacular cells on embryonic days 16. The Bowman's
      glands expressed differential patterns of immunoreactivity during development,
      beginning at postnatal day (P) 2 and P6 for Alpha and Mu classes, respectively
      and being greatest at P11 for both. The acinar cells of vomeronasal glands in the
      vomeronasal organ expressed Alpha and Mu classes of GSTs from P11 onwards. In the
      septal organ of Masera, the supranuclear region of sustentacular cells expressed
      GSTs from P11 with little or no variation during development. In the respiratory
      mucosa, Alpha and Mu classes of GSTs were detected at the brush borders of
      ciliated cells and in the acinar cells of posterior septal glands, but not in
      anterior septal or respiratory glands located on the turbinates. Compared to
      olfactory mucosa, the changes in immunoreactivity for GSTs were less pronounced
      in the respiratory mucosa during development. Specific GST Pi immunoreactivity
      was not detected in the nasal mucosae at any stage of development studied. The
      occurrence of GSTs in the nasal mucosa, including olfactory, vomeronasal, septal,
      and respiratory epithelia, suggests that the GSTs are actively involved in the
      biotransformation of xenobiotics including odorants and pheromones, and may also
      participate in perireceptor processes such as odorant clearance. In addition, we
      have developed a working model describing the cellular localization of certain
      phase I (e.g., cytochrome P-450s) and phase II (e.g., GSTs, gamma-glutamyl
      transpeptidase) biotransformation enzymes in the olfactory mucosa and their
      proposed roles in xenobiotic metabolism.

PMID- 8137397
TI  - Ultrastructural examination of the insemination reaction in Drosophila.
AB  - The insemination reaction is a swelling of the female vagina caused by the male
      ejaculate. This postmating phenomenon is common among species in the genus
      Drosophila. It could act as a plug securing male paternity. It is not clear,
      however, what benefits it provides to the female. The structure formed in the
      female vagina is expelled in some species and disappears gradually in others
      suggesting different phenomena. Based on ultrastructural examination of the
      vaginal contents of five Drosophila species (D. mettleri, D. nigrospiracula, D.
      melanogaster, D. mojavensis, and D. hexastigma), we propose three terms to
      describe these vaginal structures: the sperm sac, the mating plug, and the true
      insemination reaction. Each term describes a distinct structure associated with a
      specific female postmating behavior. This study questions the concept of the
      insemination reaction as a single phenomenon and discusses its possible functions
      from an evolutionary perspective.

PMID- 8137398
TI  - Mitochondria in fine afferent nerve fibres of the knee joint in the cat: a
      quantitative electron-microscopical examination.
AB  - The distribution of mitochondria, their content and concentration (expressed as
      the ratio of the mean volume of mitochondria and the surface of the sensory axon)
      were determined in group-III and -IV nerve fibres innervating the knee joint
      capsule in the cat. Mitochondria mainly accumulated in axonal swellings ("beads")
      and end bulbs of the terminal branches. Between single nerve fibres, marked
      differences in the content and the concentration of mitochondria were obtained in
      proximal portions (inside of the perineurium) and in distal portions
      (unmyelinated sensory endings). In group-III nerve fibres, the mitochondrial
      concentration ranged from 0.005 to 0.030 microns 3/microns 2 (proximal portion)
      and from 0.016 to 0.080 microns 3/microns 2 (distal portion). In unmyelinated
      group-IV nerve fibres, the values also showed a broad variation ranging from
      0.001 to 0.011 microns 3/microns 2 (proximal portion) and from 0.003 to 0.019
      microns 3/microns 2 (distal portion). The wide range of mitochondrial
      concentrations may reflect different energy consumption during receptive
      processes: nerve fibres with a low mechanical threshold and a high probability of
      excitatory events may be rich in mitochondria, whereas fibres with a high
      mechanical threshold and a low probability of excitatory events may be poor in
      mitochondria.

PMID- 8137399
TI  - Enhancement of seminiferous tubular growth and spermatogenesis in testes of rats
      recovering from early hypothyroidism: a quantitative study.
AB  - Testicular weight and DNA content were markedly reduced (63 and 69%) in weanling
      Long-Evans rat pups rendered hypothyroid from birth by administration of
      propylthiouracil (PTU), a reversible goitrogen. These growth deficits worsened to
      > 80% by continuing hypothyroidism beyond weaning, to days 50 and 90. Recovery of
      thyroid function, brought about by discontinuing PTU at weaning, resulted in a
      paradoxical stimulation of testis growth, amounting to increased weight (40%),
      DNA content (60%) and size by 90 days, compared to age-matched controls. In the
      25-day or older hypothyroid rats, testicular structure was immature and
      spermatogenesis markedly delayed, as evident by closed lumen and significantly
      reduced diameter of seminiferous tubules (38%), thickness of germinal layer
      (70%), and number of primary spermatocytes (86%), compared to control.
      Hypothyroidism did not alter the number of tubules per testis cross section. In
      the 90-day recovery rats, numbers of seminiferous tubules were unchanged but
      tubular diameter was significantly (20%) larger than in controls and
      spermatogenesis appeared very active as indicated by significantly increased
      germinal layer thickness (22%) and total number and density of primary
      spermatocytes (55% and 40%). The results show that although postnatal
      hypothyroidism is deleterious for testicular growth and spermatogenesis, recovery
      from this condition leads to enhanced seminiferous tubular growth and
      spermatogenesis.

PMID- 8137400
TI  - Morphological evidence of sperm maturation in the ampulla ductus deferentis of
      the bull.
AB  - The present lectin histochemical comparison of cauda epididymal and ampullary
      bovine sperm was conducted to investigate whether ampullary secretions are
      involved in altering the plasma-membrane glycoconjugates of sperm. A marked
      redistribution of glycoconjugates between sperm from these two regions was indeed
      revealed on the basis of changes in binding patterns of the following fluoroscein
      isothiocyanate (FITC)-labelled lectins: wheat-germ agglutinin (WGA), Maclura
      pomifera agglutinin (MPA), Griffonia simplicifolia I agglutinin (GS I) and
      Bauhinea purpurea agglutinin (BPA). This was evidenced in the first three cases
      by a relative reversal of staining intensity between the acrosomal and post
      acrosomal regions, and by a pronounced increase in the staining of the midpiece.
      Changes in the distribution of BPA binding sites were limited to the latter
      phenomenon. The results are compared with previous findings, discussed in the
      context of the hypermotility characteristic of ampullary sperm and related to
      previously reported differences in the lectin-binding patterns of the luminal and
      glandular epithelia.

PMID- 8137402
TI  - A monoclonal antibody (ER-HR3) against murine macrophages. I. Ontogeny,
      distribution and enzyme histochemical characterization of ER-HR3-positive cells.
AB  - We describe ER-HR3, a monoclonal antibody directed against bone marrow-derived
      haemopoietic reticulum cells. ER-HR3-positive cells have the electron-microscopic
      and enzyme-histochemical characteristics of macrophages. Additionally, they are
      able to phagocytoze. The ER-HR3 antigen is expressed by a majority of blood
      monocytes and is present on a subpopulation of resident macrophages in multiple
      organs. ER-HR3-positive cells are abundant in the bone marrow, the splenic red
      pulp, the mesenteric lymphoid paracortex and the interfollicular areas of the
      Peyer's patch. Few ER-HR3-positive cells have been observed in the thymic cortex
      and the connective tissues of the gastro-intestinal tract, the dermis and the
      renal medulla. Moreover, epidermal Langerhans cells express the antigen. No cross
      reactivity with other cell types has been found. It is concluded that ER-HR3 has
      a unique distribution pattern distinct from other macrophage-specific antibodies.

PMID- 8137401
TI  - Light- and electron-microscopic study of electrophysiologically characterized
      neurons in the mediolateral part of the lateral spetum of the guinea-pig.
AB  - In slices of guinea-pig brains, 36 neurons located in the mediolateral part of
      the lateral septum were stained intracellularly with horseradish peroxidase (n =
      28) or biocytin (n = 8) after electrophysiological characterization. These
      neurons belonged to class A neurons (n = 23), which generated pronounced Ca(++)
      dependent high-threshold spikes in control medium, or to class C neurons (n = 9),
      which were recognized by the occurrence of small-amplitude sodic spikes followed
      by slower larger calcic spikes. The present results demonstrate that, despite the
      variety of individual cell types, the major morphological population (30/36
      cells) was composed of a homogeneous class of large-sized neurons that displayed
      thick primary dendrites and abundant dendritic appendages. The remaining 6 cells
      were small-sized, poorly-spiny neurons. Somatic spines were observed on 5 out of
      the 30 large cells and on one out of the six smaller cells. Labeled axons were
      mainly oriented to the anterior commissure. The axons of nine cells richly
      collateralized near the perikaryon. Ultrastructural examination of 3 horseradish
      peroxidase-injected cells showed indented nuclei, classic organelles and somatic
      spines. Terminal boutons established symmetric synapses with the injected cells.
      These results describe the morphological features of electrophysiologically
      identified neurons and indicate that class A and class C neurons are distributed
      among morphological populations differing in perikaryal size. This suggests that
      the different electrical properties of class A and class C neurons reflect
      recordings from different parts of the neuron rather than from neurons of
      different types. Furthermore, the present findings demonstrate that, in the
      guinea-pig, electrical and morphological characteristics of somatospiny neurons
      are comparable with those of non-somatospiny neurons. Somatospiny neurons have a
      recognized integrative role in the hippocampo-septo-hypothalamic complex.

PMID- 8137403
TI  - A monoclonal antibody (ER-HR3) against murine macrophages. II. Biochemical and
      functional aspects of the ER-HR3 antigen.
AB  - We describe the purification and intracellular distribution of an antigen present
      on a subpopulation of murine macrophages and recognized by monoclonal antibody ER
      HR3 against bone marrow-derived haemopoietic reticulum cells. Using the ER-HR3
      antibody as an immobilizing ligand, two proteins were isolated as determined by
      SDS polyacrylamide gel electrophoresis. Under non-reducing conditions, there was
      a major band with an apparent molecular mass of 69 kDa and a minor band of 55
      kDa. Under reducing conditions, the apparent molecular mass of each band was
      estimated as 76 kDa and 67 kDa, respectively. Intracellularly, these proteins
      occurred in close association with membranous structures, as demonstrated with
      gold-labelled protein A in an electron-microscopic study of the ER-HR3-positive
      cell line AP284. Some of the antigen was present in vesicles. To gain further
      insight into the possible function of the ER-HR3 antigen, its tissue distribution
      was investigated under distinct experimental conditions. In mice infected with
      Bacillus Calmette Gurerin, ER-HR3-positive cells were observed in many, but not
      all, granulomata of the spleen, the lung and the liver. The ER-HR3 reactivity in
      these mice clearly differed from that of other antimacrophage monoclonal
      antibodies, such as F4/80, M5/114 and M1/70. Furthermore, phenylhydrazine-induced
      extramedullary erythropoiesis in the liver was accompanied by ER-HR3 expression
      on a subpopulation of macrophages. Finally, the addition of ER-HR3 to an antigen
      specific T cell proliferation assay did not inhibit T cell proliferation.

PMID- 8137405
TI  - [Surveillance for AIDS among key population at border ports of Guangdong in 1990
      and 1991].
AB  - A total of 260,112 persons of nine categories of key population were tested
      serologically for AIDS by the Quarantine Service in Guangdong Province and 16
      cases were found HIV-positive (one of whom was confirmed), of whom 6 were
      foreigners and 10 were Chinese returned from overseas.

PMID- 8137404
TI  - Histochemical and immunocytochemical study of the migration of neurons from the
      rat olfactory placode.
AB  - Immunocytochemical and histochemical methods have been used to describe the
      neuronal population migrating from the rat olfactory placode and to analyze the
      spatio-temporal evolution of this neuronal migration during development. Several
      neuronal markers, such as binding to the lectin Ulex europaeus (UEA I) and the
      presence of neuron-specific enolase (NSE), olfactory marker protein (OMP), and
      luteinizing hormone-releasing hormone (LHRH), have been tested in order to
      determine whether migrating neurons originate from both the medial and the
      lateral parts of the placode and whether they all express LHRH. Our data show
      that a large population of differentiated migrating neurons can be identified
      with an antibody against NSE from the 14th day of gestation and with UEA I one
      day later. Migrating neurons are closely associated with both the vomeronasal
      axon fascicles emerging from the medial pit and the olfactory axons originating
      from the lateral pit. However, the neuron migration from the lateral pit appears
      to be more discrete than that from the medial pit. No LHRH immunoreactivity has
      been detected among neurons migrating from the lateral pit. Some neurons
      accompanying the olfactory axon fascicles exhibit a high level of maturation as
      shown by their OMP-positivity. Numerous neurons positive for both NSE and UEA I
      have also been observed within the presumptive olfactory nerve layer in early
      embryonic stages.

PMID- 8137406
TI  - [Investigation on the incidence of genital herpes in different professional
      groups in Qingdao].
AB  - Genital herpes is one of 8 legally reportable sexually transmitted diseases (STD)
      in China. Using a HSV antigen ELISA kit we detected and typed HSV antigen in
      1,148 clinical specimens collected from the genital organs (penis, cervix, vagina
      and vulva) of 446 men and 702 women in Qindao and divided into 11 different
      professional and 2 special groups (patients with cervical cancer and pregnant
      women). The highest positive rate of HSV antigen was found among long-distance
      transport drivers (48.0%). The second and third high positive rates were among
      waiters and waitresses in private, restaurants (39.2%) and patients with cervical
      cancer (38.2%). The positive rates among self-employed retailers and employees in
      private inns and restaurants were notably higher than those among employees in
      state-run shops, restaurants and hotels. And, the positive rate among workers was
      higher than that among peasants. There was no notable difference between the
      positive rate of HSV antigen among men (24.2%) and that among women (21.5%). But
      the incidence of HSV-2 infection was much higher than that of HSV-1 infection.
      The results indicate that some special professional groups have high rates of
      genital HSV infection. More attention needs to be paid to these special groups in
      order to control sexually transmitted herpes diseases.

PMID- 8137408
TI  - [Epidemiologic studies on HCV and HBV infections among intravenous drug users in
      the area with high HIV infection].
AB  - To assess the prevalence of HBV and HCV infections among intravenous drug users
      (i.v. DUs) in Ruili county, Yunnan where there was a high HIV infection rate in
      i.v. DUs, the serological examination indicated that there was also a high anti
      HCV antibody positive rate in this group. Among those with anti-HIV antibody, 73
      (92%) were anti-HCV antibody positive. There was a close relationship between HIV
      infection and HCV infection. It may suggest that both are related to i.v. drug
      using. Although there is a high HBV infection background in Yunnan Province, the
      prevalence of HBV infection in i.v. DUs (68%) and that in the controls (52%)
      still show a significant difference.

PMID- 8137407
TI  - [Seroepidemiological investigations on hepatitis B virus infection in the
      populations of Han, Tibetan, Dai, Yao, Uygur, Mongol and Li nationalities].
AB  - Seroepidemiological investigations on the hepatitis B virus infection were
      carried out among populations of seven nationalities that could represent the
      main categories by the language system. The HBsAg prevalence, after sex- and age
      adjustment, was 15.3% in Han in contrast, that was 26.2% in Tibetan and 24.0% in
      Yao, being significantly higher (P < 0.001); and on the other hand, 7.0% in Li
      and 5.3% in Uygur, being significantly lower than that in Han (P < 0.001). The
      age peaks of HBsAg prevalence in Uygur and Li declined much earlier than others.
      HBeAg was not detected in women during childbearing age. The ratios of anti
      HBs/HBsAg were between 1.61 and 2.06 in general while they were only 0.82 in
      Tibetan and 1.09 in Yao.

PMID- 8137409
TI  - [The confounding factor and interaction in studies of pathogenesis--an analysis
      of the secondary infection of viral hepatitis with corticoid therapy].
AB  - A total of 762 cases of viral hepatitis admitted to the two teaching hospitals of
      the Third Military Medical College were used for study. They were divided into
      two groups depending upon whether corticoid treatment was given. As the result of
      cRR = 6.06, chi 2 = 174.16, P < 0.01, it is obvious that the corticoid therapy is
      a risk factor for the secondary infection in patients suffered from viral
      hepatitis. For getting rid of the interference of confounding factor and
      interaction a stratified analysis was performed. These patients were again
      divided into severe type and moderate type according to the severity of the
      disease. The results of stratified analysis were aRR (F) = 3.05 and aRR (F) =
      1.48, cRR > aRR. These findings demonstrated that the degree of severity of
      patients played a primary role in the secondary infection of hepatitis and showed
      that the confounding factor was present. On the other hand, the result of aRR (F)
      not equal to aRR (F) indicated that the interaction also existed simultaneously.
      This study suggests that special attention should be paid to maintain and
      increase the level of immunological defence function in patients with hepatitis.
      And, it is necessary to restrict the indiscriminate usage of corticoids,
      particularly in severe patients, for preventing nosocomial infection.

PMID- 8137410
TI  - [A preliminary study on serological differentiation between antibody against
      Brucella and that against Yersinia enterocolitica serotype O: 9].
AB  - Standard agglutination test (SAT), enzyme-linked immunosorbent assay (ELISA), dot
      immunobinding assay (DIBA) have been developed for the detection of antibodies
      against 6 strains of Brucella and that against Yersinia enterocolitica Serotype
      O: g. The results showed that differentiation could be made between Brucella and
      Yersinia O: 9 when 16M SPA, OMP and YO: 3 SPA. OMP were used by ELISA, but not
      when 104M and YO: 9 antigens were used by SAT. So, 16M and YO: 3 OMP antigens
      were better for detection of antibodies against Brucella and Yersinia O: 9 by
      ELISA.

PMID- 8137411
TI  - [Application of the mathematical model to forecast the incidence rates of
      seasonal infectious diseases].
AB  - The incidence rates of infectious diseases were selected and analysed according
      to data from the Beijing Railway Area during 1981-1991. We put forward the
      mathematical model to forecast the incidence rate of dysentery each quarter in
      1992. The best mathematical model was selected from analysis of precision, and
      very useful in the prevention and treatment of seasonal infectious diseases.

PMID- 8137412
TI  - [An epidemiological survey of hydatidosis among 27,051 persons in Shihezi
      district].
AB  - An epidemiological survey of hydatidosis was carried out among 27,051 persons in
      Shihezi District, 784 were found to be positive cases and the total standardized
      infection rate of hydatidosis was 2.84%. Among all farms, the infection rates in
      the No. 133, No. 152 and No. 135 farms were the highest. The infection rates
      among various nationalities were 6.69% (Kazak), 4.04% (Uygur), 3.42% (Hui), 2.39%
      (Han). There was a significant difference between males (2.35%) and females
      (3.33%) (P < 0.01). The young children were the majority (56.02%) among the
      positive cases. This investigation was carried out from about 1/20 of the total
      population (532,157 persons) and showed the infective state of hydatidosis in
      Shihezi District basically. The method of blood spot-ELISA on filter paper which
      was used instead of serum-ELISA simplified the procedure and cut down expenses,
      being particularly suitable for a large-scale investigation.

PMID- 8137413
TI  - [The epidemiological study of subtype risk factors of gastric cancer].
AB  - On the basis of understanding multistage pattern of the development of gastric
      cancer, we designed and carried out a new case-control study. The methods of
      analysis was multigroup logistic regression analysis. The studied objects were 4
      groups of cases and 1 group of control. They were gastric Cancer group, severe
      dysplasia group, chronic atrophic gastritis accompanied by intestinal metaplasia
      group, ulcer group and control group, respectively. The control group was
      confirmed by pathology which showed that the gastric mucosa was normal or had
      only mild chronic superficial gastritis. The results showed that the risk factors
      of gastric cancer were living in high incidence area for a long period, low
      economic income, low animal protein intake, high sweet potato and inkfish intake,
      eating and drinking too much at one meal and mental injuring. The risk factors of
      severe dysplasia were low intake of protein, intake of non-fresh fish, large
      intake of inkfish and salted meat, a family history of gastric cancer.

PMID- 8137414
TI  - [Relative risk analysis of the development of cervical noncancer lesion and
      cervical carcinoma associated with HPV infection].
AB  - Two-hundred and fourty-seven DNA samples extracted from cervical carcinoma
      tissues and 143 from cervical noncancer lesions were examined for the presence of
      human papillomavirus (HPV) type 6B, 11, 16 and 18 DNA sequences by means of dot
      blot hybridization using 32P-dCTP-labelled HPV probes (Tm-17 degrees C). The
      result showed that the overall positive rate of HPV infection in this group of
      cervical cancer was 65.99%, HPV type 16 was dominantly found in the group
      (55.06%) and accounted for 71.28% in all the positive samples of cervical
      cancers, which were 4.25 and 5.67 times higher than those of HPV type 6/11 and
      18, respectively. Detectable sequences homologous to HPVs in the cervical
      noncancer group was 51.05% and HPV types 6/11 accounted for 50.61% in the HPV
      positive samples. The relative risk analysis of HPV infection in the two groups
      was performed and the relative risk (RR) of HPV infection for development of
      cervical cancer was increased (RR = 1.86, P < 0.01). Further analysis revealed
      that HPV 16, 18 infection in cervical epithelium might be the higher risk factor
      in the development of cervical carcinoma (RR = 3.43, P < 0.001); whereas HPV type
      6/11 might be the lower risk factor for the development of cervical cancer (RR =
      0.5, P < 0.05): Our results implied that the development of cervical cancer may
      be closely associated with HPV infection, especially with HPV type 16 and 18.

PMID- 8137415
TI  - [Plasmid profiles of 120 strains of Pseudomonas aeruginosa].
AB  - The plasmid profiles of 120 clinical isolates of Pseudomonas Aeruginosa (PA) from
      Nanjing City were determined by the Kado and Liu method and the technique was
      compared with other epidemiological typing schemes based on serotype. Only 24.2%
      of these strains harbored plasmids. A total of 13 different plasmid profiles were
      observed. Plasmids varied in size from 1.91 to 45.14 MDa. The serotypability was
      95.00%. A comparison between the plasmid profiles and the serotypes might be of
      value in the epidemiologic fingerprinting of clinical isolates of PA.

PMID- 8137416
TI  - [Detection of Rickettsia tsutsugamushi DNA from chiggers by polymerase chain
      reaction].
AB  - Polymerase chain reaction was employed to detect Rickettsia tsutsugamushi DNA
      from chiggers for the first time. Both adults and larvae were tested. The
      positive rate of experimentally infected adults was 92.9%. It suggests that PCR
      is a rapid and sensitive assay for epidemiological study of scrub typhus.

PMID- 8137417
TI  - [Advances in epidemiologic study in Helicobacter pylori infection].

PMID- 8137418
TI  - [Advances in the research of alphavirus--a kind of arboviruses].

PMID- 8137419
TI  - Mice lacking nerve growth factor display perinatal loss of sensory and
      sympathetic neurons yet develop basal forebrain cholinergic neurons.
AB  - Homologous recombination was utilized to generate mice with a deletion in the
      coding sequence of the nerve growth factor (NGF) gene. Animals homozygous for NGF
      disruption failed to respond to noxious mechanical stimuli, and histological
      analysis revealed profound cell loss in both sensory and sympathetic ganglia.
      Within dorsal root ganglia, effects of the mutation appeared to be restricted to
      small and medium peptidergic neurons. These observations confirm the critical
      dependence of sensory and sympathetic neurons on NGF and demonstrate that other
      neurotrophins are not able to compensate for the loss of NGF action on these
      cells. Examination of the central nervous system revealed that, in marked
      contrast with neurons of sensory and sympathetic ganglia, basal forebrain
      cholinergic neurons differentiate and continue to express phenotypic markers for
      the life span of the null mutant mice. Thus, differentiation and initial survival
      of central NGF-responsive neurons can occur in the absence of NGF.

PMID- 8137420
TI  - p53-dependent inhibition of cyclin-dependent kinase activities in human
      fibroblasts during radiation-induced G1 arrest.
AB  - gamma-Irradiation of human diploid fibroblasts in the G1 interval caused arrest
      of the cell cycle prior to S phase. This cell cycle block was correlated with a
      lack of activation of both cyclin E-Cyclin-dependent kinase 2 (Cdk2) and cyclin A
      Cdk2 kinases and depended on wild-type p53. Although the accumulation of cyclin A
      was strongly inhibited in gamma-irradiated cells, cyclin E accumulated and bound
      Cdk2 at normal levels but remained in an inactive state. We found that both whole
      cell lysates and inactive cyclin E-Cdk2 complexes prepared from irradiated cells
      contained an activity capable of inactivating cyclin E-Cdk2 complexes. The
      protein responsible for this activity was shown to be p21CIP1/WAF1, recently
      described as a p53-inducible Cdk inhibitor. Our data suggest a model in which
      ionizing radiation confers G1 arrest via the p53-mediated induction of a Cdk
      inhibitor protein.

PMID- 8137421
TI  - JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and
      phosphorylates the c-Jun activation domain.
AB  - The ultraviolet (UV) response of mammalian cells is characterized by a rapid and
      selective increase in gene expression mediated by AP-1 and NF-kappa B. The effect
      on AP-1 transcriptional activity results, in part, from enhanced phosphorylation
      of the c-Jun NH2-terminal activation domain. Here, we describe the molecular
      cloning and characterization of JNK1, a distant relative of the MAP kinase group
      that is activated by dual phosphorylation at Thr and Tyr during the UV response.
      Significantly, Ha-Ras partially activates JNK1 and potentiates the activation
      caused by UV. JNK1 binds to the c-Jun transactivation domain and phosphorylates
      it on Ser-63 and Ser-73. Thus, JNK1 is a component of a novel signal transduction
      pathway that is activated by oncoproteins and UV irradiation. These properties
      indicate that JNK1 activation may play an important role in tumor promotion.

PMID- 8137422
TI  - An induced extracellular matrix protein reverses the polarity of band 3 in
      intercalated epithelial cells.
AB  - The intercalated epithelial cell exists in two interconvertible forms in vivo,
      one where band 3 protein is apical and the other where it is basolateral. We
      seeded an immortalized clone of these cells at low density and found that band 3
      was apical at confluence. There was little or no apical endocytosis. But when the
      cells were plated at high density, band 3 was basolateral, and there was vigorous
      apical endocytosis. Extracellular matrix produced by high density cells was able
      to retarget band 3 in low density cells and to induce apical endocytosis, as did
      a 230 kd protein partially purified from this matrix. Therefore, polarized
      targeting of some proteins is determined by external cues that might determine
      their polarity by reorganizing the cytoplasm.

PMID- 8137423
TI  - Location of stem cells of human hair follicles by clonal analysis.
AB  - We have examined the growth capacity of keratinocytes isolated from human scalp
      hair follicles. Like the keratinocytes of glabrous epidermis, most of the colony
      forming cells are classified as holoclones or meroclones when analyzed in a
      clonal assay. Some of them have extensive growth potential, as they are able to
      undergo at least 130 doublings. Therefore, the hair follicle, like the epidermis,
      contains keratinocytes with the expected property of stem cells: an extensive
      proliferative capacity permitting the generation of a large amount of epithelium.
      We have also examined the distribution of clonogenic keratinocytes within the
      hair follicle. Several hundred colony-forming cells are concentrated at a region
      below the midpoint of the follicle and outside the hair bulb. This region lies
      deeper than the site of insertion of the arrector pili muscle, which corresponds
      with the position of the bulge when the latter can be identified. In contrast,
      few colony-forming cells are present in the hair bulb, where most of the mitotic
      activity is observed during the active growth phase of the follicle. Paraclones,
      which are present both in the midregion and in the bulb of hair follicles, are
      unlikely to be the transient amplifying cells expected from kinetic studies.

PMID- 8137424
TI  - A putative cell signal encoded by the folded gastrulation gene coordinates cell
      shape changes during Drosophila gastrulation.
AB  - The folded gastrulation (fog) gene is required during Drosophila gastrulation for
      two morphogenetic movements, formation of the ventral furrow and invagination of
      the posterior midgut primordium. fog coordinates cell shape changes during these
      invaginations by inducing apical constriction of cells in spatially and
      temporally defined manners. fog is expressed in the invagination primordia in a
      pattern that precisely precedes the pattern of constrictions. Overexpression of
      fog in the dorsoanterior region of the embryo induces ectopic constrictions,
      indicating localization of fog transcripts may define domains of cell shape
      changes. fog encodes a novel protein with a putative signal sequence but no
      potential transmembrane domains. We suggest fog functions as a secreted signal
      that activates the G protein alpha subunit encoded by concertina in neighboring
      cells. Our analyses indicate that cell-cell communication ensures the rapid,
      orderly progression of constriction initiations from the middle of invagination
      primordia out toward the margins.

PMID- 8137425
TI  - C/EBP is an immediate-early gene required for the consolidation of long-term
      facilitation in Aplysia.
AB  - The consolidation of long-term memory requires protein and mRNA synthesis. A
      similar requirement has been demonstrated for learning-related synaptic
      plasticity in the gill-withdrawal reflex of Aplysia. The monosynaptic component
      of this reflex can be reconstituted in vitro, where it undergoes both short- and
      long-term increases in synaptic strength in response to serotonin (5-HT), a
      neurotransmitter released during behavioral sensitization, a simple form of
      learning. As with sensitization, the long-term synaptic modification is
      characterized by a brief consolidation period during which gene expression is
      required. We find that during this phase, the transcription factor Aplysia CCAAT
      enhancer-binding protein (ApC/EBP) is induced rapidly by 5-HT and by cAMP, even
      in the presence of protein synthesis inhibitors. Blocking the function of ApC/EBP
      blocks long-term facilitation selectively without affecting the short-term
      process. These data indicate that cAMP-inducible immediate-early genes have an
      essential role in the consolidation of stable long-term synaptic plasticity in
      Aplysia.

PMID- 8137426
TI  - TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II
      direct basal transcription on supercoiled template DNA.
AB  - YY1 is a zinc finger transcription factor whose DNA-binding motif exhibits the
      properties of an initiator element. Only three factors were required to direct
      specific basal transcription on a supercoiled template DNA carrying the YY1
      initiator: YY1, general transcription factor IIB, and RNA polymerase II. This
      minimal in vitro reaction did not require the TATA-binding protein (TBP). We
      propose that, under appropriate conditions, YY1 can function like TBP, as a
      factor that binds to the core promoter and recruits the polymerase to the
      initiation complex.

PMID- 8137427
TI  - 2.3 A crystal structure of the catalytic domain of DNA polymerase beta.
AB  - The crystal structure of the catalytic domain of rat DNA polymerase beta (pol
      beta) has been determined at 2.3 A resolution and refined to an R factor of 0.22.
      The mixed alpha/beta protein has three subdomains arranged in an overall U shape
      reminiscent of other polymerase structures. The folding topology of pol beta,
      however, is unique. Two divalent metals bind near three aspartic acid residues
      implicated in the catalytic activity. In the presence of Mn2+ and dTTP,
      interpretable electron density is seen for two metals and the triphosphate, but
      not the deoxythymidine moiety. The principal interaction of the triphosphate
      moiety is with the bound divalent metals.

PMID- 8137428
TI  - The mating-type locus of Chlamydomonas reinhardtii contains highly rearranged DNA
      sequences.
AB  - The mating-type locus of Chlamydomonas reinhardtii exists as two apparent alleles
      (mt+ and mt-) that control mating in haploid gametes and sporulation and meiosis
      in diploid mt+/mt- zygotes. Twelve genes, seven unrelated to life cycle
      transitions, are tightly linked to mt, suggesting that the locus exerts
      recombinational suppression. A 1.1 Mb chromosome walk from a gene linked to mt
      demonstrates that the mt+ and mt- loci carry four intrachromosomal
      translocations, two inversions, and large deletions and duplications within a 190
      kb sector, presumably accounting for the recombinational suppression that extends
      through 640 kb of flanking homologous DNA. The rearranged domain also carries
      blocks of mt(+)- and mt(-)-specific sequences, at least one of which includes a
      mt(+)-specific gene. The locus has the properties of an incipient sex chromosome.

PMID- 8137429
TI  - The TNF receptor superfamily of cellular and viral proteins: activation,
      costimulation, and death.

PMID- 8137430
TI  - Silencing speaks up.

PMID- 8137431
TI  - Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA
      fragmentation and apoptosis in allogeneic target cells.
AB  - We have generated H-2b mice with a homozygous null mutation in the granzyme (gzm)
      B gene. Gzm B is a neutral serine protease with Aspase activity that is found
      only in the granules of activated cytolytic T cells, natural killer cells, and
      lymphokine-activated killer cells. Gzm B-/- mice develop normally and have normal
      hematopoiesis and lymphopoiesis. In vitro, cytotoxic T lymphocytes (CTL) derived
      from gzm B-/- animals are able to induce 51Cr release from allotarget cells, but
      with reduced efficiency. However, gzm B-/- CTL have a profound defect in their
      ability to induce rapid DNA fragmentation and apoptosis in allogeneic target
      cells. This defect is kinetic since DNA fragmentation is partially compensated
      and 51Cr release is completely rescued with long incubation times. We conclude
      that gzm B serves a critical and nonredundant role for the rapid induction of
      target cell DNA fragmentation and apoptosis by alloreactive cytotoxic T
      lymphocytes.

PMID- 8137433
TI  - [Variability of vision].
AB  - The variability of the visual acuity in repeating testing using the whole-line
      method corresponds to three standardized optotype lines. A significant change of
      the visual acuity represents at least a doubling of the minimal angle of
      resolution. From the practical point of view the use of the interpolation method
      of Ferris is recommended. The mean variability of this method amounts only to 1.3
      optotype lines and its realization is based on simple mathematical operations.

PMID- 8137432
TI  - Targeted disruption of the BDNF gene perturbs brain and sensory neuron
      development but not motor neuron development.
AB  - Brain-derived neurotrophic factor (BDNF), a neurotrophin, enhances the survival
      and differentiation of several classes of neurons in vitro. To determine its
      essential functions, we have mutated the BDNF gene. Most homozygote mutants die
      within 2 days after birth, but a fraction live for 2-4 weeks. These develop
      symptoms of nervous system dysfunction, including ataxia. The BDNF mutant
      homozygotes have substantially reduced numbers of cranial and spinal sensory
      neurons. Although their central nervous systems show no gross structural
      abnormalities, expression of neuropeptide Y and calcium-binding proteins is
      altered in many neurons, suggesting they do not function normally. In contrast
      with mice lacking the BDNF receptor TrkB, motor neurons appear normal in the BDNF
      mutant.

PMID- 8137434
TI  - [Silicone implants in untreatable glaucoma].
AB  - In the last years drainage shunts for otherwise untreatable glaucoma are
      effective. An own device is described, manufactured from medical, grade silicone.
      It consists of a tube with inner diameter of 0.4 mm and outer diameter of 0.9 mm.
      This tube is inserted in a disc, resembling a contact lens with a diameter of 12
      mm, radius of 12 mm and a thickness of 0.55 mm. This part is fixed under a
      conjunctival flap between two recti muscles and the tube after proper shortening
      is introduced into the anterior chamber. The operation technique, results and
      complications in the first 11 eyes of 11 patients are reported. In 2 eyes it was
      not possible to lower the tension, in one only with additive medication. 2 eyes
      had a permanent hypotony. In 6 eyes a long term pressure normalisation was seen.

PMID- 8137435
TI  - Effectiveness of histocompatibility matching in high-risk corneal
      transplantation: a summary of results from the Collaborative Corneal
      Transplantation Studies.
AB  - The Collaborative Corneal Transplantation Studies (CCTS) were designed to
      evaluate the effect of donor-recipient histocompatibility matching and
      crossmatching on the survival of corneal transplants in high-risk patients.
      Corneas were allocated to the 419 patients in the double-masked Antigen Matching
      Study on the basis of HLA-A,-B and HLA-DR antigen match. ABO blood group
      compatibility was determined but not used for recipient selection. The 37
      patients in the Crossmatch Study were randomly assigned to receive a cornea from
      either a positively or negatively crossmatched donor. All patients received
      topical steroid therapy according to a standard protocol. Matching for HLA-A,-B
      and HLA-DR antigens had no effect on overall graft survival, the incidence of
      irreversible rejection, or the incidence of rejection episodes. The positive
      group in the Crossmatch Study had fewer graft failures, rejection failures, and
      rejection episodes than the negative group; however, these differences were not
      statistically significant. The estimated proportion of eyes with failure from
      rejection by 3 years was 30% for the ABO-incompatible group and 16% for the ABO
      compatible group (relative risk, 1.98; 95% confidence interval, 1.15 to 3.13).
      These studies demonstrate that, for high-risk patients who are immunosuppressed
      by topical steroid therapy: 1) neither HLA-A.-B nor HLA-DR antigen matching
      substantially reduced the likelihood of corneal graft failure; 2) a positive
      donor-recipient crossmatch did not increase the risk of corneal graft failure;
      and 3) ABO blood group matching may be effective in reducing the risk of graft
      failure from rejection.

PMID- 8137436
TI  - [A favorable outcome after expulsive hemorrhage in cataract surgery via a tunnel
      incision].
AB  - The authors refer about expulsive haemorrhage during cataract surgery done by
      tunnel incision in 73 years old women. She was on long term treatment for
      glaucoma and arterial hypertension. Three months after the surgery visual acuity
      was 5/7.5 with contact lens. Such a favourable outcome was achieved mainly due to
      tunnel incision. This type of incision enabled immediate wound closure, increase
      of intraocular pressure without prolapsing of eyeball content and stopping of
      expulsive haemorrhage. They recommend routine use of minimal incision capable of
      spontaneous closure for cataract surgery.

PMID- 8137437
TI  - [Microbiologic study of anterior chamber contents after cataract surgery].
AB  - The authors present an account of the results of cultivation of the contents of
      the anterior chamber at the end of cataract operations. Data assembled during 50
      operations are evaluated. The material was cultivated on solid and liquid media.
      The assembled results indicate that only cultivation from the surgical wound or
      eye contents at the end of the operation can provide a reliable picture of the
      microbial population in case of inflammatory complications.

PMID- 8137438
TI  - [Nd:YAG laser trabeculoplasty].
AB  - The results of ALT and Nd: YAG LTP are presented and compared in group 19
      patients. The average IOP reduction and increase of outflow facilities were
      significant in both methods. Any difference of results between comparing methods
      were not statistically significant.

PMID- 8137439
TI  - [Neodymium-YAG laser capsulotomy].
AB  - The results of 79 Nd: YAG capsulotomies in patients after extracapsular cataracta
      extraction are presented. The improvement in visual acuity of one or more Snellen
      lines in 94.1% eyes was observed. The complications included transitory
      hypertension more than 40 mmHg in 1.4% eyes, damage to the intraocular lens in
      40.3% eyes, disruption of the anterior hyaloid face with forward displacement of
      vitreous into capsulotomy din 38.8% eyes. The others complications like retinal
      detachment, corneal damage, hemorrhage or macular edema were not observed.

PMID- 8137440
TI  - [Exophthalmus caused by diseases of the lacrimal glands].
AB  - In the submitted paper the authors analyze data from a selected patient group
      with diseases of the orbit and evaluate the ratio of diseases of the lacrimal
      gland at the First Ophthalmological Clinic Faculty Hospital, Medical Faculty
      Comenius University in Bratislava between 1980 and 1992. During the mentioned
      period 25 patients with orbital disease were hospitalized or put on records and
      dispensarized. Tumours of the lacrimal glands were present 16 times.

PMID- 8137441
TI  - [IgG subclasses in children with recurrent respiratory diseases].
AB  - The authors examined IgG sub-classes, using the ELISA method, in 35 patients with
      relapsing respiratory diseases and 27 children of a control group aged 3-15
      years. In children with relapsing respiratory diseases without deficiency of the
      main immunoglobulin classes they found a statistically significantly reduced
      value in sub-class IgG2 (P < or = 0.01). The changes found in other sub-classes
      were not statistically significant. The authors draw attention to the fact that
      deficiency in IgG sub-classes should be considered in case of repeated
      respiratory infections caused by encapsulated microorganisms--H. influenzae, Str.
      pneumoniae--and also when reduced levels of IgG and IgA are found. However, even
      normal levels do not rule out deficiency.

PMID- 8137442
TI  - [Personal experience with treatment of congenital pes equinovarus].
AB  - The authors evaluated a group of 256 children operated in 1983-1992 at the
      Orthopaedic Clinic of the Faculty Hospital on account of congenital pes
      equinovarus. These children account for 25% of the total number of children
      treated because of this inborn defect by conservative treatment. The authors draw
      attention to the lack of uniformity of contemporary treatment of congenital pes
      equinovarus, and based on their own experience, they recommend an exact
      therapeutic plan. They emphasize the importance of early treatment by means of
      corrective plaster bandages, they describe the tactics of treatment by this
      method, as any deviation from this therapeutic pattern leads to incomplete
      elimination of the defect and to relapses. The authors present also a general
      review of possible surgical treatment and emphasize the tactics of postoperative
      treatment, incl. intensive rehabilitation and correction by footwear. They
      emphasize in particular the necessity of systematic and uninterrupted
      conservative treatment which is essential as preoperative preparation, as only by
      intensive care before and after surgery, incl. a correctly indicated and
      implemented operation, the desired goal, i.e. an anatomical position of the foot
      can be achieved.

PMID- 8137443
TI  - [C1-inhibitor plasma levels in neonates and mothers during labor].
AB  - The authors investigated C1-inhibitor (C1-INH) plasma levels in blood collected
      from mothers during delivery: mothers with a normal pregnancy and a group of
      mothers who displayed during the perinatal period direct or indirect signs of
      infectious disease. Both groups, as compared with a group of healthy donors, had
      low C1-INH levels. The neonates were divided into two groups (normal children and
      children with perinatal risk of infection) with sub-groups of mature full-term
      neonates (38-41 weeks of gestation) and premature infants (29-36 weeks of
      gestation). In the group of normal infants the neonates had on average somewhat
      lower C1-INH levels, as compared with healthy donors, in premature neonates of
      this group the lowest mean C1-INH level was recorded. In this group the authors
      observed a correlation between the inhibitor level and the gestation period. The
      results of C1-INH assessment in the group of neonates with a perinatal risk of
      infection were different. In premature neonates a higher average C1-INH level was
      observed than in mature neonates and the relationship between the C1-INH level
      and the gestation period was a linear negative regression. The postnatal increase
      of C1-INH levels on the 1st to 5th day was more rapid in premature neonates of
      both groups.

PMID- 8137444
TI  - [Transvaginal echocardiography in the early diagnosis of congenital heart defects
      in the human fetus].
AB  - Transvaginal echocardiography makes it possible to diagnose serious congenital
      heart disease already during the first trimester of pregnancy. The authors
      present their experience with this examination method in pregnant women with a
      high risk of foetal cardiopathies and in women whose foetus is affected by
      another serious organ anomaly. The authors evaluate the successful visualization
      of the cardiac anatomy in different projections in relation to foetal age. They
      present the diagnosis of a serious inborn heart disease detected during the 15th
      week of gestation.

PMID- 8137445
TI  - [Evaluation of blood flow in the renal artery and intraparenchymal arteries in
      neonates using color doppler sonography].
AB  - The authors examined 25 kidneys in 14 healthy neonates in order to evaluate the
      resistive index (RI) calculated from the maximal systolic and end-diastolic rate
      of blood flow in the renal artery and some intraparenchymatous arteries. They
      revealed a significant drop of all absolute rates of blood flow in arteries in
      the direction to the renal periphery. Consistent with rather few data in the
      literature, they assessed a normal RI value of intraparenchymatous arteries in
      healthy neonates (0.76 +/- 0.04) which differs significantly from values assessed
      in the renal artery (0.82 +/- 0.05) (p < or = 0.001). The authors discuss the
      normal RI value in the neonatal period. In the conclusion they mention that the
      RI can be obtained much more easily from the blood flow in the renal artery than
      the blood flow in intraparenchymatous arteries but the former does not reflect
      representatively the intraparenchymatous conditions in the kidneys and this
      restricts its use in evaluations of intraparenchymatous renal processes.

PMID- 8137446
TI  - [Freely moving circular shadows in the abdominal cavity--the exudative
      enteropathy syndrome?].
AB  - The authors describe a 14-year-old gypsy girl with the clinical picture of
      exudative enteropathy where they observed on X-ray examination of the abdominal
      cavity circular formations which changed position. On laparotomy they found on
      the serous membrane of the entire enlarged and inflamed ileum numerous pseudo
      polypous formations the majority of which were released and floated freely in the
      chylous ascites. The description of similar globular lesions of the lymphatic
      system was found in the literature only in accounts on post-mortem findings.

PMID- 8137447
TI  - [Recent views on the use of methotrexate in the treatment of acute lymphoblastic
      leukemia in childhood].

PMID- 8137448
TI  - [Cetirizine].

PMID- 8137449
TI  - [Liquid ventilation. 2].
AB  - The authors made two series of experiments in rabbits, using liquid ventilation.
      The first group was ventilated manually using RM 101 solution with an
      equilibration period of 30 and 60 sec., Tv = 10 ml/kg after previous
      administration of 30 ml/kg RM 101 at the beginning. The second group was
      ventilated using a specially developed liquid ventilator--part of the animals was
      ventilated with an equilibration interval of 30-90 sec., Tv = 10 ml/kg with
      administration of an initial dose od 30 ml/kg of RM 101 solution, a part of the
      animals in a continual manner, i.e. without an equilibration period and without
      administration of the initial dose of the solution. From the results it is
      apparent that the optimal way as regards blood gases and minimal manner of liquid
      ventilation. When this method was used during the 180 minutes of liquid
      ventilation paO2, paCO2 and pH were within the normal range. The other methods of
      liquid ventilation led rapidly to hypercapnia and a drop of pH as well as to
      serious changes in the circulation (hypertension, bradyarrhythmia).

PMID- 8137450
TI  - [Academician Otakar Teyschl (5 May 1891 to 10 September 1968)].

PMID- 8137451
TI  - Observations on structural features and characteristics of biological apatite
      crystals. 9. Observation on dissolution of carious enamel crystals.
AB  - In a series of studies to investigate the basic structural features and
      characteristics of the biological apatite crystals using a transmission electron
      microscope, we examined the ultrastructure of the human enamel, dentin, and bone
      crystals through the cross and longitudinal sections at near atomic resolution.
      Subsequently, using the same approach, we have been able to directly examine the
      images of the lattice imperfections in the crystal lattices of the human tooth
      and bone crystals, and the images of the fusion of the crystals. In this
      research, furthermore, using transmission and scanning electron microscopes, we
      examined the dissolution of the enamel crystals caused by the carious enamel from
      the same viewpoint. The material used for the observation of the dissolution of
      the enamel crystals was obtained from the region which corresponds to the middle
      layer of the enamel at the portion near the wall of a carious cavity caused by
      the fissure caries on the occlusal surface of the lower first molars. Small cubes
      of the materials used for the observation by transmission electron electron
      microscope were fixed in glutaraldehyde and osmium tetroxide and embedded in
      epoxy resin using the routine methods. The ultrathin sections were cut with a
      diamond knife without decalcification. The sections were examined with the
      HITACHI H-800H type transmission electron microscope operated at 200 kV. Each
      crystal was observed at an initial magnification of 300,000 times and at a final
      magnification of 10,000,000 times and over. The material used for the observation
      by the scanning electron microscope was the fractured surface obtained from the
      carious enamel. The fractured carious enamel surfaces were coated with carbon and
      gold and observed with the HITACHI HHS-2R type scanning electron microscope
      operated at 25 kV. The crystals were observed at a final magnification of 50,000
      times. As a result, we have confirmed that the dissolution of the enamel crystals
      caused by a caries occurs in the units of "hexagonal cell". We sincerely believe
      that the electron micrographs shown in this report are the first to show the
      images of the dissolution of the enamel crystals caused by a caries at near
      atomic resolution.

PMID- 8137452
TI  - F wave change by decreased motoneuronal excitability: a sleep study.
AB  - To clarify the effect of the change in motoneuronal excitability on the F wave,
      we studied the persistence, mean size, and minimum latency of the F wave in nine
      normal subjects while awake and asleep. Recordings were made from the abductor
      pollicis brevis muscle by stimulating the median nerve at the wrist. The
      persistence and size of the F wave markedly decreased during sleep, especially in
      stage REM. The mean size in stage REM was less than 5% of that in stage W in most
      subjects, and the F wave entirely disappeared in one subject. The minimum latency
      during sleep was longer than during wakefulness. Prolongation was within 2.0 ms
      when the persistence was more than 10%. A decrease in the number of motoneurons
      that elicit the F wave may be the major cause of prolongation. We conclude that
      the decreased motoneuronal excitability can cause the F wave to disappear without
      conduction block in the peripheral motor nerve and that the prolongation of the F
      wave for more than 2 ms provides a marker for proximal conduction delay in the
      clinical nerve conduction studies.

PMID- 8137454
TI  - Pharmacokinetics of doxorubicin and its active metabolite in patients with normal
      renal function and in patients on hemodialysis.
AB  - The comparative pharmacokinetics of doxorubicin (DOX) were investigated in five
      hemodialysis (HD) and eight non-hemodialysis (non-HD) patients who were infused
      with a 40- to 60-mg dose of DOX at a constant rate over 30 min. A significant
      difference was observed in the total body clearance (Cl tot) of DOX between HD
      and non-HD patients. The area under the curve (AUC) for both DOX and
      doxorubicinol (DOXol), an active metabolite, showed increases of approximately
      1.5 and 3 times in HD patients as compared with non-HD patients. Although these
      differences were not statistically significant (P < 0.1), the mean residence time
      (MRT) of DOX and DOXol in HD patients showed a 2-fold increase in comparison with
      those in non-HD patients. Compartmental analysis indicated that the greater AUC
      values and longer MRT of DOX and DOXol in HD patients resulted from the lesser
      DOXol formation and disappearance of rate constants. As a consequence of the
      decrease in Cl tot for DOX and the marginal hemodialysis clearance of both DOX
      and DOXol, the present study suggests that the exposure to DOX and DOXol obtained
      in HD patients greater than achieved in non-HD patients. Careful attention should
      therefore be paid to HD patients receiving DOX.

PMID- 8137453
TI  - Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5
      fluorouracil after oral administration of a 1:4 tegafur and uracil combination.
AB  - The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral
      preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a
      molar ratio of 1:4, were examined in 26 patients with macroscopic Stage I gastric
      cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who
      underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of
      Billroth II reconstruction) and to 9 patients who underwent total gastrectomy
      with modified Roux-en-Y reconstruction. Before the operation, the area under the
      curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28 +/- 26.88,
      4.41 +/- 1.78, and 0.51 +/- 0.20 micrograms h ml-1, respectively. Partial
      (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and
      partial gastrectomy using the Billroth I and II methods decreased the AUCs of
      uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of
      uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our
      findings show that when UFT is prescribed for patients treated in the early
      postoperative period following partial gastrectomy for cancer, dose increases and
      the timing of administration should be given close attention.

PMID- 8137455
TI  - Destruction of WiDr multicellular tumor spheroids with the novel thymidylate
      synthase inhibitor 1843U89 at physiological thymidine concentrations.
AB  - The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr
      human colon carcinoma multicellular tumor spheroids was investigated. Continuous
      exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid
      disruption, whereas 100 nM methotrexate (MTX) was required for similar effects.
      Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM
      1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to
      10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast,
      treatment with 10 or 100 nM 1843U89 for 6-48 h or treatment with 1 nM 1843U89 for
      up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM
      1843U89 in the presence of 0.05-0.3 microM thymidine was as effective in causing
      spheroid disruption as treatment in the absence of thymidine, but treatment in
      the presence of 0.7-3.0 microM thymidine caused partial reversal of spheroid
      disruption. The results of these experiments suggest that 1843U89 should have
      potent solid tumor activity in humans but should be less effective in mice due to
      differences in circulating thymidine levels (0.1 vs 1 microM, respectively).

PMID- 8137456
TI  - Variability in the pharmacokinetics of cyclophosphamide, methotrexate and 5
      fluorouracil in women receiving adjuvant treatment for breast cancer.
AB  - A total of 23 women with stage II breast cancer receiving adjuvant
      cyclophosphamide, methotrexate and 5-fluorouracil had detailed pharmacokinetic
      monitoring performed on the first and third courses of therapy. The area under
      the concentration time curve (AUC) of each of these three drugs varied by a
      factor of 3-4 among patients. No systematic change in pharmacokinetics between
      the first and third courses was seen for cyclophosphamide, methotrexate or 5
      fluorouracil, and the mean AUC for each of the three drugs did not change.
      However, significant intrapatient variability in drug pharmacokinetics was
      observed for all three drugs such that the AUC, clearance and half-life in an
      individual on the third course could not be reliably predicted from data
      generated on the first course. On the basis of these results, cyclophosphamide,
      methotrexate, and 5-fluorouracil pharmacokinetic data from one treatment would
      not be useful information from which the doses of subsequent courses could be
      determined.

PMID- 8137457
TI  - Clinical pharmacokinetics of carboplatin in children.
AB  - The present study was undertaken to evaluate in children the plasma
      pharmacokinetics of free carboplatin given at different doses and schedules and
      to evaluate the inter- and intrapatient variability and the possible influence of
      schedule on drug exposure. A total of 35 children (age range, 1-17 years) with
      malignant tumors were studied. All patients had normal renal function (creatinine
      clearance corrected for surface body area, above 70 ml min-1 m-2; range, 71-151
      ml min-1 m-2) and none had renal involvement by malignancy. Carboplatin was given
      at the following doses and schedules: 175, 400, 500, and 600 mg/m2 given as as a
      1-h infusion; 1,200 mg/m2 divided into equal doses and infused over 1 h on 2
      consecutive days; and 875 and 1,200 mg/m2 given as a 5-day continuous infusion. A
      total of 57 courses were studied. Carboplatin levels in plasma ultrafiltrate (UF)
      samples were measured both by high-performance liquid chromatography and by
      atomic absorption spectrophotometry. Following a 1-h infusion, carboplatin free
      plasma levels decayed biphasically; the disappearance half-lives, total body
      clearance, and apparent volume of distribution were similar for different doses.
      In children with normal renal function as defined by creatinemia and blood urea
      nitrogen (BUN) and creatinine clearance, we found at each dose studied a limited
      interpatient variability of the peak plasma concentration (Cmax) and the area
      under the concentration-time curve (AUC) and a linear correlation between the
      dose and both Cmax (r = 0.95) and AUC (r = 0.97). The mean value +/- SD for the
      dose-normalized AUC was 13 +/- 2 min m2 l-1 (n = 57).2+ The administration
      schedule does not seem to influence drug exposure, since prolonged i.v. infusion
      or bolus administration of 1,200 mg/m2 achieved a similar AUC (13.78 +/- 2.90 and
      15.05 +/- 1.44 mg ml-1 min, respectively). In the nine children studied during
      subsequent courses a limited interpatient variability was observed and no
      correlation (r = 0.035) was found between AUC and subsequent courses by a
      multivariate analysis of dose, AUC, and course number. The pharmacokinetic
      parameters were similar to those previously reported in adults; however, a weak
      correlation (r = 0.52, P = 0.03) between carboplatin total body clearance and
      creatinine clearance varying within the normal range was observed.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8137458
TI  - Pharmacokinetics of the anticancer agent 2-chloro-9-(2-deoxy-2-fluoro-beta-D
      arabinofuranosyl)adenine in rats.
AB  - The pharmacokinetics of a new 2-halo-2'-deoxyadenosine analogue, 2-chloro-9-(2
      deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine [CL-F-ara-A], was characterized
      in rats following the development of a new high-performance liquid chromatography
      (HPLC) technique. This halogenated derivative was thought to have improved
      gastrointestinal stability that would facilitate oral administration. The HPLC
      method consisted of a single ethyl acetate extraction and reverse-phase
      chromatographic conditions. The method resulted in approximately 83% recovery of
      CL-F-ara-A from plasma and a sensitivity of 20 ng/ml. At i.v. doses of 10 and 25
      mg/kg, the total clearance of CL-F-ara-A decreased from 2.1 to 1.5 l h-1 kg-1,
      with the reduction being attributed to saturation of metabolism. The elimination
      half-lives following i.v. bolus administrations were estimated to be a mean of
      1.35 and 1.84 h at the two respective doses. The volume of distribution at steady
      state was not significantly different at the two doses, being 3.6 and 3.2 l/kg.
      The percentage of protein binding of CL-F-ara-A in rat plasma was only 13.3%.
      Administration of equivalent oral doses resulted in bioavailability estimates of
      approximately 50%, indicating that oral treatment regimens of CL-F-ara-A are
      feasible.

PMID- 8137459
TI  - Lack of cross-resistance to a new cytotoxic arylchloroethyl urea in various drug
      resistant tumor cells.
AB  - 1-Aryl 3-(2-chloroethyl) ureas (CEUs), a new class of potent antineoplastic
      agents, were recently developed in our laboratory. These compounds were designed
      from the aromatic moiety of chlorambucil and the unnitrosated pharmacophore of
      carmustine. In the present study we investigated the effect of the potent CEU
      derivative 4-tert-butyl-[3-(2-chloroethyl)ureido] benzene (tBCEU) on tumor cell
      lines selected for resistance to a wide range of anticancer drugs. The resistance
      mechanisms found in these cells included increased expression of P-glycoprotein,
      increased intracellular concentration of glutathione and/or glutathione-S
      transferase activity, alteration of topoisomerase II, and increased DNA repair.
      Whereas the resistant cell lines were found to be highly resistant to a panel of
      clinically known anticancer drugs, tBCEU was found to be equally cytotoxic to
      both resistant and parental cells. The nitrobenzylpyridine assay indicated that
      tBCEU is a weaker alkylating agent than chlorambucil. This lack of cross
      resistance in various resistant tumor cells suggests that tBCEU could be
      potentially useful in the treatment of cancers resistant to conventional
      anticancer drugs.

PMID- 8137460
TI  - Relation between age and clearance rate of nine investigational anticancer drugs
      from phase I pharmacokinetic data.
AB  - Aging influences the disposition and effects of several classes of drugs.
      Although drug clearance rate is correlated with toxicity for many anticancer
      drugs, few data have been published concerning the relationship of aging and
      clearance of chemotherapy. This study was performed to identify any relationship
      between age and clearance rate for anticancer drugs in phase I trials at the
      Johns Hopkins Oncology Center. In a retrospective study, we examined the clinical
      and pharmacokinetic data for 344 adults (aged 21-77 years) who received 9 phase I
      drugs with linear clearance in 13 clinical trials. We sought correlations between
      age and clearance for each drug and for the whole group. Data available for 9 of
      the 13 trials were used to compare age (< 65 or > 65 years) versus dose delivered
      [< the maximum tolerated dose (MTD) vs > or = the MTD] or toxicity (< grade 3 vs
      > or = grade 3). Of 344 patients, 81 (23.5%) were > 65 years old, 34 (9.9%) were
      > or = 70 years old, and 5 (1.5%) were > or = 75 years old. There was no
      significant correlation between drug clearance and age for individual drugs or
      the group as a whole. There was no significant difference between patients of the
      older and younger age groups with regard to dose or toxicity. Although only a
      small number of patients aged > or = 75 years were treated, our results suggest
      that the elderly do not experience greater toxicity even when treated at doses
      comparable with those given younger patients and should not be excluded from
      phase I trials on the basis of age. As the population of the United States ages,
      more elderly patients will be candidates for chemotherapy. A more thorough
      examination of the relationships between age, clearance rate, and toxicity can be
      accomplished as active drugs enter phase II/III studies.

PMID- 8137461
TI  - Preclinical toxicology and tissue platinum distribution of novel oral antitumour
      platinum complexes: ammine/amine platinum(IV) dicarboxylates.
AB  - The preclinical toxicology and tissue platinum distribution of a series of six
      orally given antitumour platinum complexes [ammine/amine platinum(IV)
      dicarboxylates] with structural variations of their alicyclic amine (c-C5, c-C6
      or c-C7), axial dicarboxylate (CH3, C3H7 or NHC2H5) or leaving substituents (Cl2
      or OCOOCO) was studied in the mouse. Platinum tissue levels measured at 48 h
      after a single oral dose at 0.5 of the MTD were highest in the liver (6.0-19
      micrograms/g) and second highest in the kidney (2.8-12 micrograms/g), and these
      levels were up to 5 times higher than those reported with equi-toxic doses of
      i.v. cisplatin and i.v. carboplatin. Platinum levels in the lung, heart, spleen,
      skin, skeletal muscle and brain were all < or = 3.1 micrograms/g at this dose
      level. Liver platinum levels measured at 2 h, 2 days, 6 days and 10 days after a
      single oral dose at the MTD ranged widely (from 15 to 109 micrograms platinum/g),
      were related to the number of carbon atoms in the axial dicarboxylate and
      alicyclic amine groups (r = 0.9389) and showed a diversity of time-course
      profiles. Elevations of plasma ALT activity were recorded with single oral doses
      of JM225 and JM256 at the MTD. Accumulation of platinum in the liver with
      repeated oral dosing weekly for 4 consecutive weeks at 0.5 of the MTD occurred
      with JM269 (3.3-fold increase, P < 0.05) and JM225 (2.4-fold increase, P < 0.05),
      and elevated plasma ALT activity (44 +/- 33 IU/l) was recorded with repeated oral
      doses of JM269. JM216 was selected from this series of analogues for further
      study on the basis of the elevated plasma ALT activity (JM225, JM256 and JM269),
      liver platinum accumulation (JM269 and JM225), poor activity against human
      ovarian carcinoma xenografts (JM291) or severe emetogenesis (JM221) of other
      examples. Following a single oral dose of JM216 at the MTD, transient reductions
      in the WBC (nadir, 1.6 x 10(9)/l, 2 days, 74% reduction), platelet count (nadir,
      613 x 10(9)/l, 10 days, 33% reduction) and bone marrow cellularity (nadir, 0.5 x
      10(7) nucleated cells/femur, 4 days, 75% reduction) were found, and these had
      recovered by 21 days after treatment. Jejunal mucosal disaccharidase activity
      following single MTDs indicated that small-intestinal mucosal damage was less
      severe for oral JM216 (nadir maltase activity, 68% +/- 16% of control, NS) than
      for i.v. cisplatin (nadir maltase activity).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8137462
TI  - Uptake of doxorubicin from loaded nanoparticles in multidrug-resistant leukemic
      murine cells.
AB  - Previous studies have clearly demonstrated that polyisobutylcyanoacrylate (PIBCA)
      doxorubicin-loaded nanoparticles (NS-Dox PIBCA) can overcome the resistance of
      P388/ADR cells. In the present paper, we found that overcoming multidrug
      resistance with the aid of doxorubicin (Dox) loaded onto these nanoparticles was
      associated with an increased intracellular drug content. Indeed, after a 6-h
      incubation period, the amount of cell-associated drug was 5 times higher when the
      cells were incubated with NS-Dox PIBCA as compared with free Dox. Further
      experiments, such as uptake studies in the presence of cytochalasin B or efflux
      studies, indicated a possible mechanism of nanoparticle/cell interaction. These
      results suggested that nanoparticles did not enter the cells by an endocytic
      process, in contrast to a previous hypothesis.

PMID- 8137464
TI  - Chronic oral etoposide in advanced breast cancer.
AB  - Chronic oral etoposide has shown activity in some metastatic refractory tumors.
      To test its activity in previously treated metastatic breast cancer patients, we
      started a study in 18 consecutive patients given etoposide orally at 50 mg/m2
      daily for 21 days. A partial response was observed in 4 of 18 patients (22%); of
      the responding patients, 3 had visceral metastases and 1 had multiple bone
      metastases. Leukopenia of grade 3 or 4 was the main hematological toxic effect
      (23% of patients) and alopecia was the most important nonhematological toxicity.
      Chronic oral etoposide shows some activity in pretreated patients with metastatic
      breast cancer, with tolerance being good and toxicity, acceptable. Further
      studies of this drug given as first-line chemotherapy or in combination with
      other drugs can establish all its potential activity in this cancer.

PMID- 8137463
TI  - Cyclooxygenase and lipoxygenase inhibitors as modulators of cancer therapies.
AB  - Like many clinical non-small-cell lung cancers, the Lewis lung carcinoma produces
      prostaglandins. The Lewis lung carcinoma was used as a model of both primary and
      metastatic disease to assess the ability of cyclooxygenase inhibitors (mefenamic
      acid, diflunisal, sulindac, and indomethacin), the collagenase inhibitor
      minocycline, and the lipoxygenase inhibitor phenidone to act as modulators of
      cytotoxic cancer therapies. Although none of the single modulators given i.p.
      daily on days 4-18 altered tumor growth or the number of metastases found on day
      20, modulator combinations consisting of minocycline/a cyclooxygenase inhibitor
      and, especially, of phenidone/a cyclooxygenase inhibitor resulted in modest tumor
      growth delay and a decreased number of lung metastases on day 20. The most
      effective modulators of cisplatin (CDDP) were phenidone/sulindac and
      phenidone/indomethacin, which led to 2.4- to 2.5-fold increases in the tumor
      growth delay produced by CDDP. The most effective modulations of cyclophosphamide
      resulted from administration of minocycline, minocycline/sulindac, or
      phenidone/sulindac and led to 2.0- to 2.1-fold increases in tumor growth delay by
      cyclophosphamide. The most effective modulators of melphalan produced 4.5- to 4.7
      fold increases in tumor growth delay by the drug and were minocycline/sulindac,
      minocycline/mefenamic acid, and phenidone/sulindac. The most effective modulation
      of carmustine (BCNU) was obtained with minocycline/sulindac and
      minocycline/diflunisal leading to 2.8- to 3.1-fold increases in tumor growth
      delay by BCNU. Finally, the most effective modulation of radiation was obtained
      with minocycline/sulindac and phenidone/sulindac and resulted in 2.8- to 3.3-fold
      increases in tumor growth delay by radiation. The modulator combination that
      along with the cytotoxic therapies was most effective against metastatic disease
      was phenidone/mefenamic acid. There was no clear relationship between effective
      modulation of the cancer therapies and the degree of reduction in serum levels of
      prostaglandin E2 and leukotriene B4 by the agents in Lewis lung tumor bearing
      mice.

PMID- 8137465
TI  - Estimation of remnant liver function before hepatectomy by means of technetium
      99m-diethylenetriamine-pentaacetic acid galactosyl human albumin.
AB  - To improve the results of hepatectomy in cirrhotic patients, the likely reserve
      function of the liver was evaluated before surgery. Asialoglycoprotein receptor
      (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated
      glycoproteins. Technetium-99m-diethylene triamine pentaacetic acid-galactosyl
      human serum albumin (99mTc-GSA) is a newly developed analog ligand to ASPG-R. The
      probable functional reserve of the remnant liver after hepatectomy was estimated
      preoperatively as the hepatic binding protein (HBP) concentration specific for
      ASGP-R on the hepatocellular membrane of the remnant liver. This estimate was
      based on the effective liver volume rate, obtained by the uptake of 99mTc-GSA. In
      all, 3 normal volunteers, 3 patients with chronic hepatitis (CH), 9 patients with
      liver cirrhosis (LC), 2 patients with hepatic cystadenoma, 3 patients with
      hepatocellular carcinoma (HCC) associated with CH, and 21 HCC patients with LC
      were studied. The mean value +/- SD obtained for HBP in normal volunteers (three
      cases) and in patients with mild (four cases), moderate (two cases), and severe
      liver damage (five cases) were 0.74 +/- 0.03 microM, 0.43 +/- 0.042 microM, 0.31
      +/- 0.05 microM, and 0.20 +/- 0.05 microM, respectively. Most of the cases in
      which the preoperative HBP of the remnant liver was above 0.22 microM had a good
      postoperative course irrespective of the type of hepatectomy. On the other hand,
      in subjects with a remnant liver HBP of between 0.22 and 0.11 microM,
      postoperative severe liver dysfunction occurred in about 50% of cases. In all
      cases with a remnant liver HBP below 0.1 microM, the prognosis was very poor,
      indicating that hepatectomy should be avoided. The HBP concentration detected by
      the 99mTc-GSA study is a very sensitive indicator of changes in the hepatic
      functional reserve, and the HBP value for the functional reserve of the remnant
      liver is extremely useful for estimating the liver function before and after
      hepatectomy.

PMID- 8137466
TI  - Outcomes of 116 patients with hepatocellular carcinoma.
AB  - We studied the outcomes of 116 patients with hepatocellular carcinoma (HCC)
      diagnosed in our hospital between January 1980 and August 1992. The patients were
      divided into groups according to the principal treatment procedure. The 3-year
      survival rates in the patients treated by percutaneous ultrasonically guided
      ethanol injection (PEI), operation (hepatic resection), and transcatheter hepatic
      arterial embolization (TAE) were 90.9%, 53.6%, and 29.0%, respectively. None of
      the patients treated by one-shot injection of an anticancer agent into the
      hepatic artery and chemotherapy survived for more than 2 years. The outcomes of
      the patients treated by PEI and hepatic resection were significantly better than
      those of the patients treated by the other procedures. There was no significant
      difference when the patients were stratified according to the year of detection.
      The 3-year survival rate was 57.3% for 19 patients in whom HCCs were detected
      during clinical follow-up for chronic liver disease and 17.3% for the other 97
      patients. We concluded that hepatic resection in patients with good liver
      function and PEI for early HCC yielded significantly better survival rates than
      the other procedures. Moreover, for early detection and treatment of HCC, we
      recommend clinical follow-up of patients with chronic liver disease.

PMID- 8137467
TI  - Efficacy of CO2-DSA in embolization.
AB  - Intra-arterial digital subtraction angiography using CO2 (CO2-IA-DSA) is
      effective for detecting arteriovenous and arterioportal shunts in the liver. We
      carried out CO2-IA-DSA in addition to selective arteriography using a iodinated
      contrast medium in 31 patients with unresectable hepatocellular carcinoma (HCC).
      As a result, CO2-IA-DSA detected an AV shunt in 4/31 patients and an AP shunt in
      16/31 patients for a total of 20 cases of shunt, whereas conventional hepatic IA
      DSA detected only AP (AV shunt) shunts in 3/31 patients. For HCC without any
      shunt, Gelfoam embolization was carried out after injection of Lipiodol and
      Farmorubicin (FARM). In patients with an AP shunt, injection of Lipiodol and FARM
      was performed after the shunt had been embolized with Gelfoam. In patients with
      an AV shunt, Lipiodol and FARM were injected after the shunt had been embolized
      with a metallic coil. In conclusion, detection of shunts by CO2-IA-DSA is useful
      for determining the optimal approach for transcatheter arterial injection.

PMID- 8137468
TI  - Treatment of choice for unresectable small liver cancer: percutaneous ethanol
      injection therapy or transarterial chemoembolization therapy.
AB  - Early detection of hepatocellular carcinoma (HCC) has become easier with recent
      advances in imaging diagnosis, but the tumor is frequently unresectable due to
      underlying advanced liver cirrhosis. In this study, we evaluated the therapeutic
      effect of percutaneous ethanol injection therapy (PEIT) and transarterial
      chemoembolization therapy (TACE) for small liver cancers measuring 3 cm or less
      in diameter and discussed the treatment of choice for unresectable cases. The
      tumors were divided into two groups on the basis of size: 1.5 cm or less (group
      A) and 1.6-3 cm in diameter (group B). In group A, the estimated 1- and 3-year
      survival rates were both 82% for a total of 19 cases. The survival value
      determined for 10 patients treated with PEIT was slightly higher than that found
      for 9 patients treated with TACE. In group B, the overall 1-, 2-, and 3-year
      survival values for a total of 56 patients were estimated at 83%, 60%, and 35%,
      respectively. The survival rates for 41 patients treated with TACE were 82%, 53%,
      and 28% at 1, 2, and 3 years, respectively. PEIT was performed on only 6
      patients, whose survival rate was equivalent to that of a surgical resection
      group. The 1-, 2-, and 3-year survival rates for 9 patients who underwent
      surgical resection were estimated to be 100%, 85%, and 68%, respectively. Based
      on these results, PEIT seems to be the treatment of first choice for patients
      with small liver cancers measuring less than 1.5 cm in diameter if the tumor is
      thought to be unresectable because of associated severe liver cirrhosis. On the
      other hand, tumors measuring 1.6-3 cm in diameter must first be treated with TACE
      using a long-acting Lipiodol-carcinostatic suspension, even if resectable. In
      addition to the tumor size, dynamic CT is also useful for prospective decision of
      the therapeutic strategy. If the mass is demonstrated to be a hypervascular
      lesion by dynamic CT, TACE must be selected as the treatment of first choice,
      even for small lesions measuring 1.5 cm or less in diameter.

PMID- 8137469
TI  - Combination therapy of transcatheter chemoembolization and percutaneous ethanol
      injection therapy for unresectable hepatocellular carcinoma.
AB  - The therapeutic effectiveness of a combination therapy--pretreatment with
      transcatheter arterial chemoembolization (TACE) followed by percutaneous ethanol
      injection (PEI) therapy--for large (> 3 cm in diameter) unresectable
      hepatocellular carcinoma (HCC) was compared with that of TACE alone. PEI therapy
      was performed in 24 cases of unresectable HCC that had previously been treated
      with TACE using doxorubicin 30-60 mg or epirubicin 50-90 mg. In all, 2-10 ml of
      90% ethanol mixed with carbocaine was repeatedly injected through a 21-gauge,
      closed-end needle (PEIT needle) for a median of 3.6 injections and 31.1 ml of
      ethanol. As adverse effects, transient localized pain and a burning sensation
      were observed in 75.0% of the cases; fever, in 66.7%; and transient hypotension,
      in two cases. A small unresectable tumor is a good indication for PEI therapy. In
      cases with a larger tumor, i.e., measuring more than 3 cm in diameter, or
      multiple tumors, the 1-year survival rate obtained with this combination therapy,
      i.e., TACE and PEI, was 87.0%, and the 2-year survival rate was 65.2%. These
      rates were greater than those obtained with TACE alone. Accordingly, additional
      PEI therapy was effective for larger tumors and multiple tumors previously
      treated with TACE.

PMID- 8137470
TI  - Follow-up study of combination treatment (TAE and PEIT) for unresectable
      hepatocellular carcinoma.
AB  - The subjects were 35 patients with unresectable hepatocellular carcinoma. The
      patients were divided into a transcatheter arterial embolization group (TAE
      group, 18 cases) and a combination therapy group receiving both TAE and
      percutaneous ethanol injection therapy (TAE+PEIT group, 17 cases). The 50%
      survival period was 21.1 months for the TAE group and 37.8 months for the
      TAE+PEIT group (P < 0.05). The longest survival period in the TAE group was 89
      months. In the TAE+PEIT group, one patient has survived for 59 months. The
      actuarial 1-, 2-, and 3-year survival rates for the TAE group were 82%, 45%, and
      22%, respectively. For the TAE+PEIT group the rates were 83%, 64%, and 64%,
      respectively. The TAE+PEIT group showed a significantly higher survival rate in
      the 895- to 1,074-day period as compared with the TAE group (P < 0.05). Overall,
      the survival rate tended to be higher in the TAE-PEIT group (P < 0.1). The
      therapeutic responses of tumors were measured by the maximal reduction rate
      within 6 months of TAE and PEIT. In the TAE group, a PR was seen in only four
      cases. In the TAE+PEIT group, CRs and PRs were achieved significantly more
      frequently than in the TAE group. When the patients were divided into a responder
      group (CR, PR, and MR) and a nonresponder group (NC and PD), survival was
      significantly longer in the responder group. The findings of the present study
      suggest that the combination therapy was useful for improving the survival of
      patients with unresectable hepatocellular carcinoma.

PMID- 8137471
TI  - Surgical treatment of hepatocellular carcinoma.
AB  - The effect of surgical treatment for hepatocellular carcinoma (HCC) was evaluated
      in 149 resected cases, 83.2% of which were associated with liver cirrhosis. The 3
      and 5-year survival rates were 60.1% and 39.4%, respectively. The mortality rate
      was 4.1%. In patients aged over 70 years, liver cirrhosis was found in 53.3% of
      cases and the mortality rate was 6.7%. The 3- and 5-year survival rates were
      50.8% and 33.9%, respectively. Factors that significantly affected survival for
      more than 5 years were a tumor size of less than 3 cm, Stage I disease, vp(-),
      IMo, and diploid type. The 5-year survival rate for patients with a single tumor
      of 3 cm or less was 54.2%, regardless of the surgical procedure. All 15 patients
      with a solitary tumor of 2 cm or less (Stage I, small liver tumor) were alive
      with a 5-year survival rate of 100%. The problem is the treatment of patients
      with a tumor measuring 3-5 cm in diameter and associated liver cirrhosis, because
      their prognosis after surgery is the worst. HrS (subsegmentectomy) is the minimal
      procedure of limited hepatectomy for these cases with postoperative
      multidisciplinary therapy.

PMID- 8137472
TI  - The effect of external radiotherapy in treatment of portal vein invasion in
      hepatocellular carcinoma.
AB  - To investigate the effect of external radiotherapy in the control of portal vein
      invasion (PVI) in hepatocellular carcinoma (HCC), ten patients with cytologically
      confirmed unresectable HCC were recruited for study. All of the patients were
      assigned Pugh's classification A, and all had only unilateral PV involvement. The
      main tumors were treated by transcatheter arterial embolization. The PVI was
      irradiated with a dose of 3000-5000 cGY using a linear accelerator under
      localization by real-time ultrasound. All ten patients responded to the external
      irradiation, with complete disappearance of the PVI occurring in five and partial
      shrinkage, in the other five. However, the HCC extended to the contralateral PV
      in two patients, although the irradiated lesion had shrunk. Both patients had
      shown involvement of the main PV in the initial study. Six patients died after 3,
      6, 7, 7, 8, and 10 months, respectively, due to advance of the HCC, rupture,
      liver failure, and respiratory failure. The others survived for longer than 6
      months and remain under follow-up. The branch of PVI at discovery might have an
      important bearing on the effect of the radiotherapy. No postirradiation hepatitis
      or other complication was observed.

PMID- 8137473
TI  - Small hepatocellular carcinoma: high dose internal radiation therapy with
      superselective intra-arterial injection of I-131-labeled Lipiodol.
AB  - The aim of the present study was to deliver a high internal radiation dose to
      small hepatocellular carcinoma (HCC) lesions in an attempt to treat this disease.
      A total of 18 patients with HCC lesions measuring less than 4.5 cm in diameter
      (25 lesions) were treated with superselective intra-arterial injection of I-131
      labeled Lipiodol (370-1,100 MBq in 3-5 ml) using a 5-F or coaxial catheter. All
      the lesions were nodular, multinodular, or hypervascular on pretreatment
      angiography. In all, 15 lesions that received over 180 Gy of cumulative radiation
      decreased in size in proportion to the Lipiodol retention on CT, and no
      pericapsular recurrence was found on angiography after 14-54 months of follow-up.
      In five patients who subsequently underwent surgery, 65% to 100% tumor necrosis
      was detected. No abnormal change in liver function tests or untoward clinical
      symptom of the lung, thyroid, or bone marrow was detected in patients who
      survived for more than 3 years after the treatment. Superselective high-dose
      internal radiation therapy of small HCC offers hope of treatment and long-term
      local control without complications.

PMID- 8137474
TI  - Repeated arterial infusion chemotherapy for inoperable hepatocellular carcinoma
      using an implantable drug delivery system.
AB  - Arterial infusion chemotherapy has become one of the major treatments for
      malignant tumors. Since 1988, we have attempted repeated arterial infusion of
      anticancer drugs using an implantable drug delivery system in 68 patients who had
      inoperable hepatocellular carcinoma (HCC). Most of our patients could not undergo
      transcatheter arterial embolization (TAE) because of extreme tumor extension
      and/or accompanying advanced liver cirrhosis. In most patients we implanted a 5-F
      catheter via the femoral artery nonsurgically and connected it to a
      subcutaneously implanted drug delivery system without any difficulty. The
      treatment consisted of weekly or biweekly intrahepatic one-shot administration of
      anticancer drugs. As one therapeutic regimen, epirubicin was given alone. Other
      regimens consisted of combined chemotherapy using two or more of the following
      drugs: mitomycin C. Adriamycin, 5-fluorouracil, cisplatin, and epirubicin. In
      some cases, these drugs mixed with Lipiodol were given for targeting and slow
      release in the liver. The response rate (CR+PR) of the cases was 25.0%. The
      median survival period was 389.9 days. The 6-month, 1-year, and 2-year survival
      rates were 75%, 45%, and 17%, respectively. There was no severe side effect or
      complication except arterial occlusion that precluded further infusion
      chemotherapy. We think that the implantable drug delivery system will contribute
      not only to improved therapeutic efficacy for inoperable HCC but also to an
      improved quality of life for the patients.

PMID- 8137475
TI  - Effects of hepatic arterial infusion chemotherapy on unresectable or recurrent
      hepatocellular carcinoma.
AB  - We performed hepatic arterial infusion chemotherapy (HAI) on 86 patients with
      unresectable hepatocellular carcinoma (HCC, 61 patients) or unresectable
      recurrent HCC after hepatectomy (25 patients). As drug therapy, 250 mg of 5
      fluorouracil was injected daily for 14 days using a reservoir embedded in the
      subcutaneous layer. During this period, 0.4 mg/kg of doxorubicin and 0.12 mg/kg
      of mitomycin C suspended in Lipiodol Ultra-Fluide were also injected twice intra
      arterially. This was defined as one course of HAI, and it was repeated every 3
      months. In the patients with unresectable HCC, the 1-, 2-, and 3-year survival
      rates were 31.5%, 22.4%, and 10.7%, respectively, and the numbers of cases
      showing a complete response (CR), a partial response (PR), a minor response (MR),
      no change (NC), and progressive disease (PD) according to the Criteria for the
      Evaluation of the Clinical Effects of Solid Cancer Chemotherapy established by
      the Japan Society for Cancer Therapy were 1 (1.6%), 20 (32.8%), 5 (8.2%), 28
      (45.9%), and 7 (11.5%), respectively. On the other hand, the 1-, 2-, and 3-year
      survival rates of the patients with unresectable recurrent HCC were 69.6%, 34.8%,
      and 14.9%, respectively. The rate of catheter patency after 1 year was 64.1%, and
      the mean catheter-patency period was 311.9 days. Patients in group A (CR+PR, n =
      21) survived significantly longer than those in group B (MR+NC+PD, n = 40; P <
      0.05). In conclusion, since responders to HAI achieve longer survival than
      nonresponders, the selection of effective drugs is important for this therapy.

PMID- 8137476
TI  - Hepatic arterial infusion chemotherapy for liver metastases from breast cancer.
AB  - Between 1985 and 1992, 56 patients with unresectable liver metastases from breast
      cancer were treated by repeated hepatic arterial infusion chemotherapy employing
      an implantable port system. 5-Fluorouracil (5-FU) at 330 mg/m2 per week.
      Adriamycin (ADR) at 20 mg/m2 every 4 weeks, and mitomycin C (MMC) at 2.7 mg/m2
      every 2 weeks were given to 42 patients. The remaining 14 patients received 5-FU
      at 330 mg/m2 per week and epirubicin (EPIR) at 20 mg/m2 every 2 weeks. As a rule,
      the treatment was performed on an outpatient basis. The side effects and
      complications observed included myelosuppression (41%), hepatic arterial
      occlusion (23%), and gastric mucositis (20%), but no major toxicity was
      encountered. The response rate (CR+PR) of the evaluated patients as determined
      from CT scans was 81%. The overall median survival period was 12.5 months. Only
      14% of the patients died due to regrowth of liver metastases, and in 70% of the
      total cases, death due to liver metastases was avoided by this treatment. Thus,
      repeated hepatic arterial infusion chemotherapy for liver metastases from breast
      cancer might be capable of prolonging the survival of patients via avoidance of
      death due to the liver metastases.

PMID- 8137477
TI  - Clinical study of biological response modifiers as maintenance therapy for
      hepatocellular carcinoma.
AB  - We conducted a randomized, controlled trial comparing 5-fluorouracil (5-FU) with
      or without biological response modifiers (BRMs) as a maintenance therapy for
      hepatocellular carcinoma (HCC) after treatment with percutaneous ethanol
      injection (PEI), transcatheter arterial embolization (TAE) or arterial infusion
      of antitumor agents (AI). A total of 58 cases of HCC were classified into 4
      groups as follows: group I, PSK with 5-FU (n = 15); group II, lentinan with 5-FU
      (n = 15); group III, OK-432 with 5-FU (n = 12); and group IV, 5-FU alone as the
      control (n = 16). The mean survival time, mortality rate, time to progression,
      and T4/T8 ratio of lymphocytes in the peripheral blood were compared among the
      four groups. There was no significant difference in the background factors among
      the groups. In group I, the T4/T8 ratio of lymphocytes was reduced after the
      therapy. No significant difference was found among the groups in terms of the
      mean survival time, mortality rate, or time to progression. PEI for initial
      therapy was superior to the other therapies in terms of the mean survival time
      and mortality rate. These results suggest that the addition of BRM to maintenance
      therapy with 5-FU exerts no prognostic benefit on HCC patients treated with PEI,
      TAE, or AI.

PMID- 8137478
TI  - A randomized trial of intrahepatic arterial infusion of 4'-epidoxorubicin with
      Lipiodol versus 4'-epidoxorubicin alone in the treatment of hepatocellular
      carcinoma.
AB  - We conducted a prospective randomized trial to evaluate the efficacy of Lipiodol
      in intrahepatic arterial infusion chemotherapy for patients with hepatocellular
      carcinoma (HCC). A total of 38 patients with unresectable HCCs and underlying
      cirrhosis were entered in this trial, and 36 of them were evaluable. Every 4
      weeks, 17 patients received 70 mg of 4'-epidoxorubicin (epirubicin) alone (group
      A), whereas 19 patients received a Lipiodol emulsion containing the same dose of
      epirubicin (group B) through the hepatic artery. A tumor response (CR+PR) was
      observed in 12% of group A patients and in 42% of group B patients. The group B
      patients showed a significantly higher response rate than the group A patients.
      There was a tendency for an increased duration of survival (P = 0.09) in the
      group B patients. These results suggested that the infusion of the Lipiodol
      emulsion with epirubicin was more effective than epirubicin alone for the
      treatment of these patients with HCC.

PMID- 8137479
TI  - Hepatic resections for primary liver cancer.
AB  - The medical records of 399 patients who underwent hepatic resection between
      January 1981 and December 1990 were reviewed. Information regarding the results
      of the hepatic resection in terms of the operative indication, operative
      procedure, operative morbidity, and mortality was abstracted. As of the end of
      1990, a total of 402 hepatic resections had been completed, including those of
      319 primary malignancies, 4 secondary malignancies, 2 gallbladder carcinomas, 42
      cases of intrahepatic cholelithiasis, and 35 benign masses. Major hepatic
      resections were performed on 117 patients (29%), of whom 60 (51%) had
      histologically proven liver cirrhosis. Minor hepatic resections were performed on
      the remaining 285 patients (71%). Sepsis was the most frequent complication,
      which manifested primarily as wound infection (71 cases) or intra-abdominal
      infection (25 cases). Nonfatal hepatic failure occurred in nine patients with
      cirrhosis and one patient without cirrhosis. There were 38 operative deaths among
      the 402 hepatic resections, for an overall operative mortality of 9.4%; 25 of
      those deaths were due to hepatic failure after the operation, accounting for 66%
      of the total operative mortality. There was an increasing frequency of hepatic
      resection during the last 5 years. The indication for resection due to
      hepatocellular carcinoma increased from 87 to 195 cases. The cumulative data show
      a decrease in the incidence of complications and the operative mortality rate. In
      the most recent period, nonlethal postoperative complications occurred in 135 of
      286 patients (47%). The overall 1-, 3-, and 5-year survival rates for 172
      patients, excluding cases of operative mortality, palliative resection, and re
      resection, were 71.0%, 39.8%, and 28.3%, respectively.

PMID- 8137480
TI  - Prognosis after hepatic resection in patients with hepatocellular carcinoma,
      estimated on the basis of the morphometric indices.
AB  - To determine whether the morphometric indices of hepatocellular carcinoma (HCC)
      correlated with the prognoses, the microscopic morphometric values for 84 HCC
      cases treated by hepatic resection were studied using an image analyzer in
      relation to the survival rate and the gross classification. The mean survival
      time (MST) was 58 months in cases with a nucleocytoplasmic area ratio (N/C) of
      less than 0.28; this was significantly longer than the 38-month MST in cases with
      an N/C of more than 0.28 (P < 0.05). In stage III disease, the MST for cases with
      an N/C of less than 0.28 was 63 months, which was significantly longer than the
      MST of 13 months for cases with an N/C of more than 0.28. After relatively
      noncurative hepatic resection, the MST for cases with an N/C of less than 0.28
      was 49 months, and this was significantly longer than the MST of 8 months for
      cases with an N/C of more than 0.28. The MST was 71 months for cases with a
      coefficient of variance of the nuclear form factor (NCV) of less than 5.5%, which
      was significantly longer than the MST of 33 months for cases with an NCV of more
      than 5.5% (P < 0.05). In stage III disease, the MST was 69 months for cases with
      an NCV of less than 5.5%, and this was significantly longer than the MST of 29
      months for cases with an NCV of more than 5.5% (P < 0.05). In cases with an N/C
      of less than 0.28, 18% had vascular invasion and 38% had intrahepatic metastases,
      whereas in those with an N/C of more than 0.28, 62% had vascular invasion and 67%
      had intrahepatic metastases (P < 0.01, P < 0.05). Based on the results of these
      morphometric studies on HCC cases treated by hepatic resection, N/C and NCV may
      be useful as prognostic factors.

PMID- 8137481
TI  - Regulating factors of liver regeneration after hepatectomy.
AB  - The factors regulating liver regeneration were studied by measuring changes in
      the liver volume and serum hepatocyte growth factor (HGF) levels after
      hepatectomy. Changes in the liver volumes were studied in 68 hepatectomized
      patients, including (A) hepatoma patients who had chronic hepatitis or liver
      cirrhosis (n = 44) and (B) metastatic liver cancer patients who had normal liver
      parenchyma (n = 24). The hepatic volume increased by 13.8% of the remnant hepatic
      volume in group A and by 49.1% in group B. The examined factors included the
      percentage of resected liver volume (%RLV) and the results of laboratory tests.
      Regression analysis showed that in group A, both %RLV (beta = 0.46) and the serum
      total bilirubin (T-Bil) level (beta = -0.33) correlated significantly with the
      extent of liver regeneration and that in group B, only %RLV (beta = 0.78)
      correlated significantly with the regeneration. Serum HGF levels after
      hepatectomy were studied in 21 hepatectomized patients, including 11 hepatoma
      patients and 10 patients with some types of metastatic liver cancer. Serum HGF
      levels increased significantly after surgery in all 21 patients. Regression
      analysis, however, showed that the change in HGF was related to liver cirrhosis
      (beta = 0.46) and to the maximal postoperative T-Bil level (beta = 0.51) but not
      to the extent of liver regeneration after hepatectomy. These results suggest that
      liver regeneration is regulated primarily by factors relating to the percentage
      of the resected liver parenchyma and that serum HGF levels do not directly relate
      to liver regeneration after surgery.

PMID- 8137482
TI  - Determination of tumour vascularity using selective hepatic angiography as
      compared with intrahepatic-arterial technetium-99m macroaggregated albumin scan
      in hepatocellular carcinoma.
AB  - A total of 51 patients with hepatocellular carcinoma (HCC) were studied to
      determine the tumour vascularity as determined by selective hepatic angiography
      (HAG) and by intrahepatic-arterial technetium-99m-labeled macroaggregated albumin
      (Tc99m-MAA) scan. The tumour vascularity was graded on the HAG films by an
      interventional radiologist using a scale ranging from 1 (hypovascular) to 4
      (extremely hypervascular). The grades of vascularity on HAG were grade 1 in 5
      patients, grade 2 in 13 patients, grade 3 in 24 patients and grade 4 in 9
      patients. The tumour vascularity on scintigraphy was determined by quantifying
      the count rates over the tumour and normal liver areas by an analog/digital gamma
      camera, and the resultant tumour-to-normal ratio (T/N ratio) gave a quantitative
      measure of the vascularity. The range of the T/N ratio was 0.9 to 11.1, with a
      median of 3.7. There was no correlation between the tumour vascularity grading on
      HAG and the T/N ratio on the Tc99m-MAA scan (Wilcoxon rank test, P = 0.83). Thus,
      we conclude that HAG cannot reveal the true vascularity nor reflect the T/N ratio
      in HCC.

PMID- 8137483
TI  - Changes in portal hemodynamics and hepatic function after partial splenic
      embolization (PSE) and percutaneous transhepatic obliteration (PTO).
AB  - Since April 1985, we have performed a multidisciplinary therapy consisting of
      partial splenic embolization (PSE), percutaneous transhepatic obliteration (PTO)
      or transileocolic vein obliteration (TIO), and endoscopic injection sclerotherapy
      (EIS) for patients with severe gastroesophageal varices and those with a
      portacaval shunt associated with portal hypertension. In this study, PSE and
      percutaneous transhepatic portography (PTP) were performed at the same time in
      seven liver cirrhosis patients with hypersplenism, gastroesophageal varices, or
      hepatocellular carcinoma. The changes in portal blood flow/pressure and
      hemodynamics were examined by a thermodilution method. The effects of PSE on
      blood biochemical parameters such as the platelet count, ICG R15, redox tolerance
      index (RTI), and oral glucose tolerance test (75 g OGTT) were also evaluated. PSE
      induced a decrease in the blood flow of the splenic artery and in the splenic
      vein pressure without decreasing the portal blood flow. The platelet count in the
      peripheral blood and the RTI increased significantly. These results suggest the
      possibility that PSE may reduce the potential perioperative risk in
      hepatocellular carcinoma complicated with liver cirrhosis.

PMID- 8137484
TI  - Intra-arterial alcoholization of advanced hepatocellular carcinoma.
AB  - For the purpose of achieving emergency hemostasis of a ruptured hepatocellular
      carcinoma (HCC) or prevention of such rupture, we applied a new method of
      transcatheter therapy: intra-arterial alcoholization. Five patients with a
      ruptured HCC and 42 with an impending rupture were treated by intra-arterial
      injection of absolute ethanol mixed with an equal volume of iodized oil, Lipiodol
      (EtOH-Lp). The tumor size ranged from 4 to 26 cm (mean 7.8 cm) in diameter. The
      catheter tip was placed in the segmental branch or a more distal position of the
      hepatic artery, and 2-40 (mean 10.6) ml of EtOH-Lp was infused under fluoroscopic
      guidance. Infiltration of ethanol into the HCC mass was recognized as a dense
      deposition of Lipiodol on plain abdominal X-rays and computed-tomography. In all
      five cases of ruptured HCC, hemostasis was achieved. In all 42 cases of impending
      rupture, tumor rupture was prevented, and all except 3 patients could be
      discharged. No significant complication of the gastrointestinal tract or biliary
      tract was seen. The incidence and severity of postembolization syndrome was
      markedly lower than those seen in cases treated with Gelfoam embolization.

PMID- 8137485
TI  - New development of transarterial immunoembolization (TIE) for therapy of
      hepatocellular carcinoma with intrahepatic metastases.
AB  - The prognosis of patients with multiple hepatocellular carcinoma (HCC) remains
      disappointing. In this study, we devised a new therapeutic modality for HCC
      consisting of transarterial immunoembolization (TIE) using OK-432 and fibrinogen
      and then analyzed the preliminary results. In the first series, we applied the
      treatment to 19 patients with advanced HCC who had proved to be insensitive to
      several previous conventional treatments. In all, 14 patients (74%) with
      unresected HCC have currently survived for between 2 and 16 months after TIE. The
      remaining 5 patients died at 17, 14, 8, 7, and 4 months after TIE. The serum
      levels of tumor markers decreased in all of the patients, and a marked reduction
      in tumor size was observed in six patients after TIE. A high fever occurred in
      all cases, and abdominal pain and loss of appetite were also observed after TIE.
      However, deterioration of liver function was negligible. After confirmation of
      the safety of this method, we started a second study series in which this TIE
      treatment was selected as the first choice. Six patients have been treated to
      date. All patients in this group underwent hepatic resection at 6-48 days
      following TIE. Histological examination of the resected specimens following TIE
      showed massive infiltration of mononuclear cells around tumor cell nests and
      lytic necrosis as well as coagulation necrosis of the main tumor and the
      intrahepatic metastases. In conclusion, our results indicate that TIE may be a
      safe and promising therapy for patients with HCC.

PMID- 8137486
TI  - Effective cases of transcatheter arterioportal chemoembolization with high-dose
      iodized oil for hepatocellular carcinoma.
AB  - By administering an excessive amount of iodized oil via the hepatic artery,
      anticancer drugs in the iodized oil flow into the portal vein through the
      arterioportal communication. This phenomenon permits chemotherapy against
      extracapsular infiltration by a hepatocellular carcinoma (HCC) nourished by the
      portal blood flow. From May 1983 through July 1992, 240 cases of HCC underwent
      transcatheter arterioportal chemoembolization (TAPCE) with more than 5 ml of
      iodized oil (mean, 15 ml) in our hospital. In all, 32 patients survived for more
      than 3 years, and the factors favoring the efficacy of TAPCE therapy were
      investigated. Doxorubicin (mean, 46 mg) was given to 31 patients and 20 mg
      mitomycin C was given to 1 patient. The patients included one Stage 1 case, 13
      Stage 2 cases, 17 Stage 3 cases, and one Stage 4 case. The mean tumor size was
      5.0 cm, and portal invasion was suggested in 8 cases by angiography. The tumors
      were divided into 5 types: 13 cases of the single nodular type (SN), 7 cases of
      the single nodular type with proliferation (SN-P), 3 cases of the multinodular
      fused type (MN-F), 5 cases of the multinodular type (MN), and 4 cases of the
      massive type. A complication of liver dysfunction was detected in 14 cases, and
      half of them were Child's class C. In all, 7 patients underwent hepatectomy and 6
      received percutaneous ethanol injection after TAPCE. The treated area of TAPCE
      was classified as segmental, lobar, or total. Segmental and lobar administration
      of TAPCE yielded statistically effective results, and their tumor response rate
      was 86%. All of the MN-F and massive types showed a good tumor response. The
      incidence of intrahepatic distant metastasis was higher in the localized TAPCE
      group than in the total TAPCE group. Segmental and lobar TAPCE should be applied
      for localized infiltrating HCCs, even in cases associated with liver cirrhosis,
      but these methods have a limited capacity to prevent distant intrahepatic
      metastasis.

PMID- 8137487
TI  - Marked clinical improvement in patients with hepatocellular carcinoma by surgical
      removal of extended tumor mass in right atrium and pulmonary arteries.
AB  - Two patients with advanced hepatocellular carcinoma presented severe exertional
      dyspnea because of extension of a tumor into the right side of the heart.
      Removable of the tumor thrombus by open-heart surgery ameliorated the symptoms in
      each case, but their subsequent courses differed considerably. One patient
      survived for as long as 8 months thanks to successive multi-disciplinary
      treatments, whereas the other patient died suddenly 1 month after the surgery.
      The first patient's hepatocellular carcinoma was more differentiated, and the
      dyspnea was caused by a low cardiac output due to the intracardiac tumor mass,
      not by pulmonary embolism as in the second patient's case. We conclude that
      successive multidisciplinary treatments to control the growth of hepatocellular
      carcinoma is the most important approach and is indispensable for improving the
      prognosis.

PMID- 8137488
TI  - Therapeutic effect of a CDDP-epirubicin-Lipiodol emulsion on advanced
      hepatocellular carcinoma.
AB  - Prior injection of an anticancer agent and Lipiodol mixture is a key point for
      the treatment of hepatocellular carcinoma (HCC). We therefore prepared a new,
      improved emulsion of Lipiodol containing a high dose of cis
      diamminedichloroplatinum (CDDP) and epirubicin by replacing the ionic contrast
      medium (Urografin 67) with a nonionic contrast medium (Iopamidol; Iopamiron 300)
      and adding phosphatidyl choline. This CDDP-epirubicin-Lipiodol emulsion (CELE)
      was examined pharmacologically and chemically with the following results. The
      size of these particles is less than 10 microns (diameter) for up to 24 h; the
      release of 28%-34% of the CDDP and 80%-90% of the epirubicin was estimated in the
      dissolution test, and 85% of the CDDP and 35% of the epirubicin was retained in
      the organs in the moment calculation. CELE was injected into 58 HCC patients via
      a celiac angiographic catheter. In 36 of these patients, the CELE injection was
      followed by transcatheter arterial embolization (TAE) therapy. Following the
      administration of CELE as one-shot injection therapy for stage IV HCC, the 1-year
      survival rate was 59% and the 2-year survival rate was 27%. Moreover, in patients
      (stage II, 12; stage III, 8; stage IV, 16) who received CELE and subsequently
      underwent TAE therapy, the 1-year survival rate was 90% and the 2-year survival
      rate was 67%. The nonionic contrast medium with Lipiodol forms finer emulsified
      particles, and these particles are more capable of penetrating into the tumor. In
      addition, the greater pharmacological stability of these particles provides a
      slow-release effect and prolonged stability of their shape. Finally,
      theoretically, the use of two major anticancer agents such as CDDP and epirubicin
      showed a greater clinical effect in the treatment of HCC than either our earlier
      suspension or a single anticancer agent.

PMID- 8137489
TI  - Combination therapy consisting of arterial infusion chemotherapy (EPF, EAP) and
      transcatheter arterial embolization (TAE).
AB  - From January 1988 to January 1993, 45 patients with unresectable advanced
      hepatocellular carcinoma (HCC) were treated with a new combination therapy
      consisting of arterial infusion chemotherapy and TAE. The combination therapy was
      performed according to our treatment schedule as follows: two courses of arterial
      infusion chemotherapy were given first, and then transcatheter arterial
      embolization (TAE) using a mixture of Lipiodol and cisplatin powder was
      performed. Two arterial infusion chemotherapeutic regimens were employed: EPF
      (etoposide, cisplatin, and 5-fluorouracil) and EAP (etoposide, Adriamycin or Epi
      adriamycin, and cisplatin). The anticancer drugs were infused through a catheter
      inserted into the proper or common hepatic artery. Assessment was made of the
      anticancer effect and survival rate of each treatment method. The response to
      each therapy was evaluated on the basis of CT performed prior to and after the
      treatment. In the EPF.TAE group, the response rate was about 46%, whereas in the
      EAP.TAE group it was 48%. Overall, 21 of 45 patients attained a regression rate
      of 50% or more. Furthermore, daughter nodules decreased in size or disappeared in
      about 67% of 15 patients. Additionally, tumor thrombi tended to show a similar
      response. In all of the cases, the average duration of survival was 30.3 months,
      and the 1-year survival value was 68%, the 2-year survival value was 44%, and the
      3-year survival value was 35%. These results were superior to those obtained with
      TAE therapy alone.

PMID- 8137490
TI  - Subsegmental transcatheter arterial embolization for small hepatocellular
      carcinomas: local therapeutic effect and 5-year survival rate.
AB  - The local therapeutic effects and 5-year survival rates obtained following
      subsegmental transcatheter arterial embolization (TAE) therapy for small
      hepatocellular carcinomas (HCCs) were retrospectively analyzed. A total of 124
      nodular-type HCC lesions measuring less than 4 cm in diameter in 100 patients
      with liver cirrhosis were subjected to the analysis. All lesions became opaque on
      digital subtraction angiography. Complete necrosis was seen in 64% of 11 resected
      lesions. Among the remaining 113 lesions, the 1- and 5-year local recurrence
      rates following one performance of TAE were 18% and 33%, respectively. The 1- and
      5-year survival rates were 100% and 53%, respectively. No significant side effect
      was observed after TAE therapy. Subsegmental TAE therapy significantly improved
      the long-term survival rates of patients with small HCCs associated with liver
      cirrhosis as compared with those treated by conventional TAE therapy.

PMID- 8137491
TI  - Five-year survival after transcatheter chemoembolization for hepatocellular
      carcinoma.
AB  - The 5-year cumulative survival rate of 443 patients who underwent transcatheter
      chemoembolization (TCE) for non-resectable hepatocellular carcinoma (HCC) before
      December 1986 was 8.0%, and 29 patients survived for 5 years or more. Of these 29
      patients, 25 were men and 4 were women; their mean age was 63.9 years.
      Macroscopic classification showed lesions of the single nodular type in 16 cases,
      the multiple nodular type in 10 cases, and the massive type in 3 cases; 12 of the
      single nodular lesions measured 5 cm or less in size. The TNM classification
      showed lesions of stage I in 3 cases, stage II in 14 cases, stage III in 6 cases,
      and stage IV in 6 cases. Lesions classified as Child A were found in 23 patients,
      and they were thus much more common than Child B lesions (2 patients) and Child C
      lesions (1 patient). The response was analyzed in relation to the use of iodized
      oil (Lipiodol). It was used in 215 of the patients, and the 5-year cumulative
      survival rate of those patients was 12.9% (23 of them survived for 5 years or
      more). Lipiodol was not used in 228 patients, and they showed a 5-year cumulative
      survival rate of 3.4%, with 6 patients surviving for 5 years or more. The 6
      patients with stage III disease and the 6 with stage IV disease received
      Lipiodol. TCE with Lipiodol thus contributed greatly in prolonging the survival
      of patients with HCC complicated by intrahepatic metastases or intraportal tumor
      thrombi.

PMID- 8137492
TI  - Prospective and randomized controlled study of chemoembolization therapy in
      patients with advanced hepatocellular carcinoma. Cooperative Study Group for
      Liver Cancer Treatment in Shikoku area.
AB  - The Cooperative Study Group conducted a study to assess the therapeutic effects
      of chemoembolization in patients with advanced hepatocellular carcinoma (HCC)
      using either epirubicin hydrochloride (FARM) or doxorubicin hydrochloride (ADR).
      A total of 77 patients were enrolled in this study and randomized into 2 groups:
      39 patients were treated with a FARM solution as the material for Lipiodol
      transcatheter arterial embolization (TAE; FARM group), and 38 patients were
      treated with an ADR solution as the material for L-TAE (ADR group). For the FARM
      group, the 1-year survival rate was 69.9% and the 2-year survival rate was 44.5%.
      For the ADR group, the corresponding survival rates were 74.7% and 44.0%. The
      differences among the above figures were not statistically significant. As side
      effects, fever, nausea, and generalized fatigue occurred at almost the same
      frequencies in the two groups. Changes detected in the liver function and the
      peripheral blood cell count in both groups were not severe. There was no
      significant difference between the toxic effects observed in the two groups. In
      conclusion, there was no significant difference in therapeutic efficacy between
      the FARM and ADR groups.

PMID- 8137493
TI  - Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.

PMID- 8137494
TI  - Lysophosphatidylcholine in oxidized low-density lipoprotein increases endothelial
      susceptibility to polymorphonuclear leukocyte-induced endothelial dysfunction in
      porcine coronary arteries. Role of protein kinase C.
AB  - We have shown that transferred lysophosphatidylcholine (lysoPC) from oxidized low
      density lipoprotein (Ox-LDL) to endothelial surface membrane activates protein
      kinase C (PKC) in endothelial cells, suggesting that Ox-LDL could alter
      endothelial functions through PKC activation. The purposes of the present study
      were to examine whether the endothelial susceptibility to polymorphonuclear
      leukocytes (PMNs) may be altered in Ox-LDL-treated coronary arteries, which have
      properties closely resembling those observed in atherosclerotic arteries, and to
      determine the mechanism(s) by which Ox-LDL may affect the endothelial
      susceptibility to PMNs. Isolated porcine coronary arteries were cannulated and
      perfused with oxygenated culture medium with or without LDLs or lipids at a
      constant flow (37 degrees C, pH 7.4). The treatment of porcine coronary arteries
      with Ox-LDL increased endothelial adhesiveness to PMNs and augmented PMN-induced
      impairment of endothelium-dependent arterial relaxation (EDR). Furthermore, Ox
      LDL stimulated the expression of intercellular adhesion molecule-1 (ICAM-1) in
      the porcine coronary arterial endothelium. These effects of Ox-LDL were not
      mediated by the scavenger-receptor-mediated process but were attributed to lysoPC
      in Ox-LDL. Blocking of the PMN adherence to endothelium by using anti-CD18
      monoclonal antibody abolished the PMN-induced impairment of EDR. Coincubation
      with staurosporine or calphostin C, inhibitors of PKC, during treatment of the
      arteries with Ox-LDL or lysoPC attenuated the augmentative effects of Ox-LDL and
      lysoPC on endothelial ICAM-1 expression, endothelial adhesiveness to PMNs, and
      PMN-induced EDR impairment. Treatment of the arteries with phorbol 12-myristate
      13-acetate, a potent stimulator of PKC, induced ICAM-1 expression and enhanced
      the endothelial adhesiveness to PMNs and PMN-induced EDR impairment, mimicking
      the effects of Ox-LDL. These results suggest that lysoPC in Ox-LDL induces
      endothelial ICAM-1 expression, which facilitates PMN adherence to endothelium and
      the subsequent augmentation of PMN-induced EDR impairment. PKC activation in
      endothelial cells by lysoPC in Ox-LDL may at least in part be involved in these
      effects of Ox-LDL. LysoPC in Ox-LDL increases endothelial susceptibility to PMN
      induced endothelial dysfunction.

PMID- 8137495
TI  - Brain "ouabain" mediates the sympathoexcitatory and hypertensive effects of high
      sodium intake in Dahl salt-sensitive rats.
AB  - To assess whether brain ouabain-like activity (OLA) mediates the hypertensive
      effects of high sodium intake in Dahl salt-sensitive (Dahl S) rats, the effects
      of blockade of brain OLA on mean arterial pressure (MAP) and renal sympathetic
      nerve activity (RSNA) were evaluated in conscious Dahl salt-resistant (Dahl R)
      and Dahl S rats on a regular (120 mumol/g) or high sodium (1370 mumol/g) diet
      from 4 to 7 weeks of age. Dahl S rats given high sodium showed higher basal MAP
      and augmented responses of MAP and RSNA to air stress and to
      intracerebroventricular injection of the alpha 2-adrenergic receptor agonist
      guanabenz as compared with Dahl R rats or Dahl S rats given regular sodium. In
      contrast, the sympathoexcitatory and pressor responses to intracerebroventricular
      injection of ouabain (0.3 and 1.0 microgram) were markedly attenuated in Dahl S
      rats given high sodium. Intracerebroventricular preinjection of 0.3 microgram
      ouabain significantly enhanced blood pressure and RSNA responses to air stress
      and intracerebroventricular guanabenz in Dahl S rats given regular sodium to the
      levels observed in Dahl S rats given high sodium. Intracerebroventricular digoxin
      specific antibody Fab (DAF) fragments (132 micrograms/8 microL for 5 minutes) did
      not change basal MAP and RSNA during the first 4 hours after administration in
      Dahl S rats on a high sodium diet for 3 weeks. However, 18 hours after the
      injection of DAF fragments, basal MAP and RSNA were significantly decreased,
      reaching values for Dahl S rats on a regular sodium diet. The magnitude of
      increases or decreases in MAP and RSNA to air stress or intracerebroventricular
      guanabenz were significantly attenuated by the DAF fragments in Dahl S rats on a
      high sodium but not regular sodium diet. Concomitant intracerebroventricular
      infusion of DAF fragments (200 micrograms per day) prevented the development of
      hypertension after a high sodium diet in Dahl S rats and prevented an
      augmentation in pressor and sympathoexcitatory responses to air stress. After
      discontinuing the infusion of DAF fragments, resting MAP gradually increased to
      the high levels found in Dahl S rats given high sodium treated with gamma
      globulins. These results support the concept that high sodium intake may cause
      hypertension in Dahl S rats by increasing endogenous brain OLA, thereby enhancing
      sympathetic outflow and basal blood pressure as well as sympathoexcitatory and
      pressor responses to stress.

PMID- 8137496
TI  - Changes in type VI adenylyl cyclase isoform expression correlate with a decreased
      capacity for cAMP generation in the aging ventricle.
AB  - We investigated the developmental regulation of the beta-adrenergic receptor-Gs
      adenylyl cyclase pathway in myocardial membranes from fetal, neonatal, adult, and
      mature adult rats by measuring the density of the beta-adrenergic receptor and
      the activities of the stimulatory guanine nucleotide-binding protein Gs and the
      adenylyl cyclase enzyme. Total beta-adrenergic receptor content (in femtomoles
      per milligram protein) was greatest in the fetal (124.4 +/- 20.5 fmol/mg) and
      neonatal (122.3 +/- 16.1 fmol/mg) stages and gradually decreased in the adult
      (90.9 +/- 8.0 fmol/mg) and mature adult (70.0 +/- 9.6 fmol/mg) stages. An
      equivalent pattern was seen for adenylyl cyclase activity: the basal activity of
      the effector enzyme or that measured in the presence of 0.1 mmol/L isoproterenol
      with 0.1 mmol/L Gpp(NH)p, 10 mmol/L NaF, or 0.05 mmol/L forskolin was greater in
      the fetus and the neonate than in the adult and the mature adult. These data
      suggested that decreased stimulation of the catalytic unit by Gs could be the
      underlying cause of diminished adenylyl cyclase activity with aging. However,
      quantification of Gs by reconstitution into S49 cyc- membranes (in picomoles cAMP
      per microgram for 10 minutes) demonstrated no significant decrease during
      development from fetus (1.55 +/- 0.1 pmol/microgram) to neonate (1.9 +/- 0.5
      pmol/microgram) and subsequent aging to adult (2.6 +/- 0.2 pmol/micrograms) and
      mature adult (1.9 +/- 0.2 pmol/microgram). When Northern blot analysis was used
      to characterize the relative amounts of mRNA coding for Gs alpha, no significant
      differences were seen among the developmental stages studied.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8137497
TI  - Subthreshold stimulation of Purkinje fibers interrupts ventricular tachycardia in
      intact hearts. Experimental study with voltage-sensitive dyes and imaging
      techniques.
AB  - The effects of subthreshold stimulation (STS) delivered during right atrial
      pacing and ventricular tachycardia (VT) were investigated in Langendorff-perfused
      guinea pig hearts. The hearts were stained with a voltage-sensitive dye (RH 421)
      to map the propagation of optical action potentials. Sustained VT was reliably
      induced by 5-second trains (cycle length [CL], 25 to 50 milliseconds; duration,
      0.5 to 10 milliseconds; and voltage, 2x threshold voltage) of impulses (n = 12
      hearts) or a single premature beat (n = 6). The location of extrastimuli was not
      critical to the induction of VT, but the diameter of the heart had to be > or =
      14.5 mm. During VT, heart rate increased from 200 to 600 beats per minute; action
      potential durations decreased from 112 to 175 milliseconds to 60 to 105
      milliseconds, with no diastolic interval. Activation on the epicardium spread
      anisotropically, but VT decreased the "apparent" maximum conduction velocity
      (theta max) by 68% and altered the orientation of the major axis from beat to
      beat. Activation patterns and theta max measured during VT were similar to
      patterns recorded during direct pacing of the ventricle and indicated that
      Purkinje fibers no longer propelled ventricular excitation. STS (CL, 25 to 50
      milliseconds; duration, 0.5 to 25 milliseconds; and voltage, 0.5x to 0.8x
      threshold; trains of 2.0 to 2.5 seconds) interrupted VT when applied to Purkinje
      fibers lining the endocardium (n = 6) but failed to interrupt VT when applied to
      the epicardium (n = 8). In atrial pacing, STS delivered to the endocardium
      increased theta max from 2.44 +/- 0.32 (mean +/- SEM) to 3.63 +/- 0.21 m/s in a
      local region surrounding the first activation sites (n = 4). Alternatively, VT
      could be terminated by reducing theta max (approximately 55%) with procainamide
      (10 mumol/L) (n = 6). STS terminates VT by synchronizing ventricular excitation
      most likely by increasing local conduction and/or improving the coupling between
      Purkinje and ventricular cells.

PMID- 8137498
TI  - Short-term diabetes alters K+ currents in rat ventricular myocytes.
AB  - The electrophysiological properties of single ventricular myocytes from control
      rats and from rats made diabetic by streptozotocin (STZ) injection (100 mg/kg
      body weight) have been investigated using whole-cell voltage-clamp measurements.
      Our major goal was to define the effects of diabetes on rate-dependent changes in
      action potential duration and the underlying outward K+ currents. As early as 4
      to 6 days after STZ treatment, significant elevation of plasma glucose levels
      occurs, and the action potential duration increases. In both control and diabetic
      rats, when the stimulation rate is increased, the action potential is prolonged,
      but this lengthening is considerably more pronounced in myocytes from diabetic
      rats. In ventricular myocytes from diabetic rats, the Ca(2+)-independent
      transient outward K+ current (I(t)) is reduced in amplitude, and its reactivation
      kinetics are slowed. These changes result in a smaller I(t) at physiological
      heart rates. The steady-state outward K+ current (IK) also exhibits rate
      dependent attenuation, and this phenomenon is more pronounced in cells from
      diabetic rats. These STZ-induced changes in I(t) and IK also develop when a lower
      dose (55 mg/kg) of STZ is used and measurements are made after 7 weeks of
      treatment. These electrophysiological effects are not related to the hypothyroid
      conditions that accompany the diabetic state, since they cannot be reversed by
      replacement of the hormone L-triiodothyronine to physiological levels. Direct
      effects of STZ could be ruled out, since preceding the STZ injection with a bolus
      injection of 3-O-methylglucose, which prevents development of hyperglycemia,
      prevents the electrophysiological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137499
TI  - Inhibition of nitric oxide production aggravates myocardial hypoperfusion during
      exercise in the presence of a coronary artery stenosis.
AB  - Regulation of coronary vasomotor tone during myocardial hypoperfusion is
      incompletely understood. The present study was performed to test the hypothesis
      that endogenous production of nitric oxide contributes to resistance vessel
      dilation distal to a coronary artery stenosis that results in myocardial ischemia
      during exercise. Seven dogs instrumented with a Doppler velocity probe, hydraulic
      occluder, and indwelling microcatheter in the left anterior descending coronary
      artery (LAD) were studied during treadmill exercise in the presence of a coronary
      artery stenosis before and after intracoronary infusion of NG-nitro-L-arginine
      (LNNA, 20 mg/kg). This dose of LNNA inhibited the maximal increase in LAD flow
      produced by intracoronary acetylcholine by 82 +/- 5% but did not alter the
      response to intracoronary nitroprusside. Coronary pressure distal to the stenosis
      was maintained constant during the control period and after administration of
      LNNA. LNNA increased aortic and left ventricular systolic and end-diastolic
      pressures at rest and during exercise. During control in the absence of a
      stenosis, LNNA had no effect on coronary blood flow. In the presence of a
      stenosis that decreased distal coronary pressure to 55 +/- 2 mm Hg, mean
      myocardial blood flow measured with microspheres was 1.09 +/- 0.13 mL.min-1.g-1
      in the LAD-dependent and 2.57 +/- 0.50 mL.min-1.g-1 in the posterior control
      region, respectively. With no change in distal coronary pressure, LNNA decreased
      mean myocardial blood flow in the LAD region to 0.68 +/- 0.11 mL.min-1.g-1 (P <
      .01). To avoid systemic hemodynamic effects, LNNA was administered in a dose of
      1.5 mg/kg IC to four additional dogs. This low dose inhibited the coronary blood
      flow increases produced by acetylcholine by 61 +/- 5% but was devoid of systemic
      hemodynamic effects. During exercise in the presence of a coronary stenosis that
      decreased coronary pressure to 52 +/- 1 mm Hg, this dose of LNNA decreased mean
      myocardial blood flow from 0.89 +/- 0.23 to 0.66 +/- 0.21 mL.min-1.g-1 (P < .02).
      These data demonstrate that nitric oxide contributes to the maintenance of
      myocardial perfusion distal to a flow-limiting coronary artery stenosis during
      exercise.

PMID- 8137500
TI  - Input impedance of the lower abdominal aorta in chronically instrumented fetal
      sheep.
AB  - Five fetal sheep (gestational age, 118 to 125 days) were instrumented to measure
      impedances of the lower abdominal aorta. Four days after surgery, flow and
      pressure pulses were recorded during control conditions and during infusion of
      norepinephrine (0.3 to 3 micrograms.min-1.kg-1 body weight) or angiotensin II
      (0.2 to 3 micrograms.min-1.kg-1). The protocol was repeated after injection of
      hexamethonium (10 mg.kg-1). Moduli and phases of impedances for the first ten
      harmonics were calculated by fast Fourier transformation. During control, input
      resistance was 4300 +/- 940 dyne.s.cm-5 (mean +/- SD) at a mean blood flow of
      13.3 +/- 2.4 cm3.s-1 and pressure of 54,960 +/- 6980 dyne.cm-2. Moduli fell to
      50% of input resistance between 2 and 3 Hz and, declining continuously, reached a
      minimum of 20% near 10 to 12 Hz, then increased slightly to 30% at about 30 Hz.
      At the first three harmonics, flow was always leading pressure. Infusion of
      angiotensin or norepinephrine increased impedance moduli significantly.
      Resistance increase was largest with angiotensin (19,800 +/- 11,370 dyne.s.cm-5),
      but no difference was detectable between angiotensin and norepinephrine when
      related to the same increase of input resistance. The position of the minimum
      seemed to be unchanged at high resistance values, but relative impedance moduli
      were smaller than during control, and low-frequency phases were significantly
      more negative. An analog of inertance, compliance, and resistance to steady flow
      was used to simulate impedances, and the effect of resistance increases on flow
      waveforms in the fetal abdominal aorta was calculated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8137501
TI  - Ascorbyl free radical as a real-time marker of free radical generation in briefly
      ischemic and reperfused hearts. An electron paramagnetic resonance study.
AB  - The role of free radicals in myocardial reperfusion injury remains controversial.
      We have developed a new method using ascorbyl free radical (AFR) as a real-time,
      quantitative marker of free radical generation during myocardial reperfusion. A
      total of 35 dogs were studied. Twelve open-chest dogs underwent either 5 minutes
      (n = 5) or 20 minutes (n = 7) of coronary artery occlusion and 30 minutes of
      reperfusion. Seven additional animals undergoing 20 minutes of coronary occlusion
      also received the antioxidant enzymes superoxide dismutase and catalase,
      beginning 10 minutes before occlusion through the end of reperfusion. Exogenous
      ascorbate was infused intravenously, and the concentration of AFR in the great
      cardiac vein was continuously measured by electron paramagnetic resonance
      spectroscopy. Preocclusion AFR concentration was similar in the three groups.
      Upon reperfusion, AFR rose significantly in each animal group (P < .05). However,
      the AFR rise in the 20-minute-occlusion group, 38 +/- 17%, was significantly
      greater than in the 5-minute-occlusion group, 27 +/- 14% (P < .002). In addition,
      in the animals that received superoxide dismutase and catalase, the rise in the
      AFR was markedly attenuated, 13 +/- 6% (P < .002). Two dogs that received
      ascorbate but did not undergo coronary artery occlusion/reperfusion sequences
      showed no change in coronary venous AFR signal, indicating the stability of the
      signal over time. Five dogs received ascorbate while undergoing interventions to
      alter coronary venous flow: intravenous saline, dobutamine, dipyridamole, and
      nitroglycerin. Coronary venous AFR changes were minimal despite large coronary
      flow alterations, indicating that the AFR signal is independent of changes in
      coronary venous flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137502
TI  - Phasic secretion of newly synthesized atrial natriuretic factor from unstimulated
      atrial myocytes in culture.
AB  - We have examined kinetics and composition of newly synthesized proteins secreted
      from cultured atrial myocytes from adult rats. Under unstimulated conditions,
      noncontracting cultured atrial myocytes, which were pulse-labeled for 10 minutes
      with [35S]methionine, rapidly released a considerable portion of newly
      synthesized atrial natriuretic factor (ANF) in a phasic secretion with a peak at
      40 to 80 minutes of chase time. The phasic secretion almost ceased after 80
      minutes of chase, after which relatively slow release of the hormone was
      observed. The ability to stimulate the phasic secretion with secretagogues and a
      marked resemblance of the radiochemical composition of released proteins in the
      unstimulated phasic secretion to that in stimulated secretion suggest that the
      proteins discharged from the cells during the phasic secretion might be derived
      from secretory granules. Examination of the quantitative change of intracellular
      ANF showed that approximately 60% of newly synthesized labeled ANF was still
      retained in the cells after the termination of the phasic secretion, indicating
      that the termination of the phasic secretion was not due to depletion of the
      labeled protein in the cells. These results suggest that a proportion of newly
      synthesized ANF was rapidly released from the unstimulated atrial myocytes via a
      secretory route that shares certain features with both the regulated and the
      constitutive secretory pathway and that a part of newly synthesized ANF is
      processed for rapid release while the remainder is destined for slow release or
      storage within the cells.

PMID- 8137503
TI  - Immunologic identification of Na+,K(+)-ATPase isoforms in myocardium. Isoform
      change in deoxycorticosterone acetate-salt hypertension.
AB  - There are three isoforms of the catalytic (alpha) subunit of the Na+,K(+)-ATPase,
      each derived from a different gene, that differ in their sensitivity to
      inhibition by cardiac glycosides. Antibodies specific for the three isoforms were
      used to study Na+,K(+)-ATPase isoform expression in ventricular myocardium, where
      an understanding of digitalis receptor diversity is most important. In the rat
      heart, there is simultaneous expression of two isoforms in adult ventricle, and
      immunofluorescence studies demonstrated that both isoforms are expressed
      uniformly in cardiomyocytes. Hypertension and hypertrophy have been reported to
      selectively depress alpha 2 isoform mRNA levels, and we show in the present study
      that alpha 2 protein levels were correspondingly depressed in rats made
      hypertensive by uninephrectomy and treatment with deoxycorticosterone acetate and
      a high-salt diet. In the human heart, where mRNA for all three alpha isoforms has
      been reported, we detected all three isoform proteins (alpha 1, alpha 2, and
      alpha 3). Two isoforms (alpha 1 and alpha 3) predominated in the macaque heart;
      dissection of the heart showed uniformity of isoform expression in different
      ventricular regions but markedly less alpha 3 in the atrium. Finally, isoform
      specific antibodies were used to detect which alpha isoforms were expressed in
      the ventricles of several commonly used experimental animals to test the
      correlation of isoform expression with cardiac glycoside-response heterogeneity.
      Two isoforms (alpha 1 and alpha 3) were found in canine myocardium, whereas only
      one (alpha 1) was found in sheep and guinea pig. Expression of Na+,K(+)-ATPase
      isoforms can thus be readily followed and related to the physiology of the
      digitalis receptor.

PMID- 8137504
TI  - Regulation of fos and jun immediate-early genes by redox or metabolic stress in
      cardiac myocytes.
AB  - We have previously demonstrated coordinate inductions of c-fos, c-jun, jun B, and
      jun D in cardiac myocytes exposed to hypoxia for 2 to 4 hours. Induction of these
      transcripts occurred before any significant loss of intracellular ATP. In the
      present study, the origin of the signal(s) that regulates immediate-early gene
      induction was investigated by comparing the effects of hypoxia with those of the
      metabolic inhibitors cyanide, deoxyglucose and cyanide combined, and iodoacetic
      acid. Cyanide, an inhibitor of oxidative metabolism, closely mimicked the
      metabolic effects of hypoxia, with elimination of oxygen consumption, increased
      lactate production, and minimal decline in ATP levels under both conditions.
      Compared with hypoxia, cyanide mediated small transient inductions of fos and jun
      transcripts that followed a different time course. The combination of cyanide and
      deoxyglucose resulted in inhibition of lactate production as well as respiration,
      and ATP dropped rapidly to 20% of control levels. The loss of intracellular ATP
      was followed by fourfold inductions of c-fos and c-jun with minor changes in jun
      B and jun D transcript levels. Similarly, iodoacetic acid caused a major (90%)
      loss of ATP and irreversible cell damage as measured by leakage of creatine
      phosphokinase enzyme and loss of membrane arachidonic acid; ATP loss was followed
      by fivefold to sevenfold inductions of c-fos, c-jun and jun B
      transcripts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137505
TI  - Imipramine blocks rapidly activating and delays slowly activating K+ current
      activation in guinea pig ventricular myocytes.
AB  - Imipramine is a tricyclic antidepressant drug that also exhibits antiarrhythmic
      effects and whose clinical spectrum of activity is similar to that of quinidine.
      It has been previously demonstrated that imipramine inhibits the aggregate time
      dependent outward K+ current (IK). IK is composed of at least two components: a
      slowly activating La(3+)-resistant delayed rectifying current (IK,s) and a
      rapidly activating La(3+)-sensitive current (IK,r). To assess the effects of
      imipramine on IK,r and IK,s, single guinea pig ventricular myocytes were studied
      using the nystatin-perforated patch-clamp technique in the absence and in the
      presence of La3+. Imipramine inhibited IK,r and IK,s in a concentration-dependent
      manner. The effects of imipramine on the aggregate time-dependent outward current
      were more marked than those on IK,s alone. Thus, 1 mumol/L imipramine decreased
      the tail currents elicited on return to -30 mV after long depolarizing pulses (5
      seconds, from -40 to +50 mV) in the absence and in the presence of La3+ by 27 +/-
      4% and 15 +/- 3% (n = 6), respectively. Moreover, the inhibition induced by
      imipramine was greater after short (0.5-second) pulses than after 5-second
      depolarizing pulses, both in the absence and in the presence of La3+ (53 +/- 3%
      and 30 +/- 5%, respectively; n = 6; P < .05). Imipramine did not significantly
      modify either the activation midpoint or the slope factor of the aggregate IK and
      IK,s activation curves. The reduction of IK,s by imipramine was voltage dependent
      and was more marked at negative membrane potentials. In the presence of 1 mumol/L
      imipramine, the ratio of tail current to time-dependent current remained constant
      at 0.37 +/- 0.03, regardless of the test pulse duration at +50 mV. Thus, the
      envelope-of-tails test was satisfied in the presence of 1 mumol/L imipramine,
      which indicates that imipramine, at this concentration, blocks IK,r. Imipramine
      (1, 5, and 10 mumol/L) had no effect on the kinetics of the later phase of IK
      activation but delayed the beginning of the activation of IK,s by 62 +/- 22, 74
      +/- 23, and 155 +/- 53 milliseconds in the presence of 1, 5, and 10 mumol/L
      imipramine, respectively. These results suggest that imipramine preferentially
      blocks rapidly activating K+ channels. In addition, experiments performed in the
      presence of 30 mumol/L La3+ suggest that the drug preferentially binds, but maybe
      not exclusively, to a closed state of the slowly activating K+ channel.

PMID- 8137506
TI  - Effect of extracellular ATP on the Na+ current in rat ventricular myocytes.
AB  - Extracellular ATP concentration can rise because of its release by nerve
      terminals and by damaged cells during ischemia. After the activation of P2
      purinergic receptors, ATP induces a positive inotropic effect and increases the L
      type Ca2+ current via activation of a Gs protein but without cAMP production. In
      addition, ATP shifts the voltage characteristics of Ca2+ current toward
      hyperpolarized potentials. If ATP produced similar effects on the Na+ current
      (INa), this compound should also affect cardiac excitability and conduction.
      Using the whole-cell patch-clamp to record INa in rat ventricular cells, we show
      that extracellular application of ATP induced hyperpolarizing shifts in the
      current-voltage relation and the availability of INa. The ED50 for the shifts in
      both conductance and availability was obtained with 0.7 mumol/L ATP. Maximal
      shifts in conductance and availability were respectively 9.7 +/- 0.6 and 10.6 +/-
      0.7 mV. The leftward shift of the availability curve is responsible for the
      decrease of INa amplitude at less polarized holding potentials. These effects
      were not cholera toxin sensitive and thus cannot be attributed to activation of
      the Gs protein. At 100 mumol/L, ATP gamma S and alpha,beta-methylene ATP could
      induce shift, whereas UTP and beta,gamma-methylene ATP as well as ADP and
      adenosine were without effect. Thus, depending on the resting membrane potential,
      ATP should either enhance excitability or favor slow conduction and weaken
      cardiac electrical homogeneity and consequently favor arrhythmia.

PMID- 8137508
TI  - Angiotensin II induces fibronectin expression associated with cardiac fibrosis in
      the rat.
AB  - Fibronectin expression was studied in the heart of rats given a continuous
      infusion of angiotensin II (Ang II). Northern blot analysis showed that left
      ventricular fibronectin steady-state mRNA increased fivefold to eightfold in
      response to pressor doses of Ang II after 24 hours. Accumulation of
      immunodetectable fibronectin in the ventricles occurred after the mRNA levels
      increased. The changes in fibronectin expression were reversible when Ang II
      treatment was withdrawn. The Ang II-induced increase in fibronectin mRNA
      accompanied similar increases for collagen type I, collagen type IV, and atrial
      natriuretic factor steady-state mRNA. Interstitial and perivascular fibrosis was
      identified in both ventricles of angiotensin-treated rats within 3 days. In situ
      hybridization identified cells associated with areas of fibrosis as the principal
      site of fibronectin mRNA accumulation in treated animals. By comparison, normal
      hearts showed fibronectin expression primarily within ventricular vascular tissue
      and the atrial endocardium. A dose-dependent reduction of fibronectin expression
      followed treatment with losartan, indicating an Ang II type 1 receptor-mediated
      effect. Normalization of blood pressure during Ang II infusion by either
      hydralazine or prazosin had different effects on the level of fibronectin steady
      state mRNA, indicating that blood pressure elevation was not the principal factor
      responsible for fibronectin induction. Concurrent administration of angiotensin
      converting enzyme inhibitors with Ang II attenuated the increased fibronectin
      expression. Our data indicate that Ang II induces an acute fibrotic response
      within the heart and suggests that Ang II stimulates fibronectin expression
      within nonmyocytic cardiac cells by a direct action.

PMID- 8137507
TI  - Effects of phosphorylation of troponin I and C protein on isometric tension and
      velocity of unloaded shortening in skinned single cardiac myocytes from rats.
AB  - Effects on isometric tension generation and maximum velocity of unloaded
      shortening after exposure to cAMP-dependent protein kinase (PKA) were
      investigated in rat enzymatically isolated, tritonized ventricular myocytes.
      Exposure of myocytes to PKA in the presence of [32P]ATP resulted in
      phosphorylation of troponin I and C protein. Ca2+ sensitivity of isometric
      tension was assessed as pCa50, ie, the [Ca2+] at which tension was 50% of
      maximum, and was lower after PKA treatment (pCa50 5.58) than before PKA treatment
      (pCa50 5.74). This suggests beta-adrenergic stimulation of the heart and
      subsequent increases in PKA activity and phosphorylation of troponin I and C
      protein lead to a significant decrease in tension-generating ability at a given
      submaximum [Ca2+]. Unloaded shortening velocity was determined by measuring the
      time required to take up various amounts of slack imposed at one end of the
      cardiac myocyte preparation. Unloaded shortening velocity during maximum
      activation was 2.88 +/- 0.11 muscle lengths per second (mean +/- SEM) before PKA
      exposure and 2.86 +/- 0.13 muscle lengths per second after PKA exposure. Unloaded
      shortening velocity during 40% of maximum activation was 1.91 +/- 0.25 muscle
      lengths per second before PKA exposure and 2.17 +/- 0.15 muscle lengths per
      second after PKA exposure. The absence of an effect of PKA on unloaded shortening
      velocity in skinned ventricular myocytes suggests that beta-adrenergic
      stimulation of myocardium either does not affect myofilament velocity of
      shortening or alters velocity of shortening by a non-PKA-dependent process.

PMID- 8137509
TI  - Alpha-skeletal actin is associated with increased contractility in the mouse
      heart.
AB  - BALB/c mice express abnormally high levels of alpha-skeletal actin in the heart,
      which may be related to a duplication in the promoter of the alpha-cardiac actin
      gene. To evaluate the effects of overexpression of the alpha-skeletal actin
      isoform on cardiac contractile function, we studied these mice using the isolated
      perfused work-performing murine heart model and measured actin isoform expression
      in the same hearts. We quantified myocardial contractility from the maximum rate
      of contraction (+dP/dt) and time to peak pressure and relaxation from -dP/dt and
      time to half relaxation of left intraventricular pressure. Dot blots of total RNA
      hybridized against oligonucleotide sequences specific for either alpha-skeletal
      or alpha-cardiac actin mRNA showed that increased levels of alpha-skeletal actin
      RNA correlated significantly with increased contractility of hearts from the
      BALB/c mice (r = .80, n = 15, P < .001). The present study demonstrates a
      significant functional correlation between alpha-actin isoform content and
      cardiac contractile function and also that alpha-skeletal actin may promote an
      increased contractile function in the heart compared with alpha-cardiac actin.

PMID- 8137510
TI  - Hemodynamics in transgenic mice with overexpression of atrial natriuretic factor.
AB  - The circulatory effects associated with lifelong plasma atrial natriuretic factor
      (ANF) elevation were examined by generating transgenic mice, which constitutively
      express a fusion gene consisting of the transthyretin promoter and the ANF
      structural gene. These mice have chronically elevated ANF levels as compared with
      their nontransgenic siblings. Transgenic animals exhibited immunoreactive ANF
      levels that were nearly fivefold higher than those measured in nontransgenic
      littermates. Systemic and regional hemodynamics and blood volumes were explored
      by using modifications of the reference microsphere and dilution techniques. Mean
      arterial pressure was reduced by 24 mm Hg, associated with a 27% reduction in
      total heart weight. This chronic reduction in blood pressure was due to a 21%
      reduction in total peripheral resistance, whereas cardiac output, stroke volume,
      and heart rate were not significantly altered, despite a 15% elevation in plasma
      volume. Transgenic mice displayed reductions of 35%, 33%, 32%, and 19% in muscle,
      skin, brain, and renal vascular resistance, respectively, whereas coronary and
      splanchnic resistances were not significantly altered. The findings complement
      earlier data from chronically infused normotensive mammals and suggest that these
      mice are an excellent model for investigating the effects of lifelong ANF
      elevation.

PMID- 8137511
TI  - Characterization of muscarinic acetylcholine receptors expressed by an atrial
      cell line derived from a transgenic mouse tumor.
AB  - The properties of muscarinic acetylcholine receptors in the cell line MCM1,
      derived from an SV40 T-antigen-induced atrial tumor in a transgenic mouse, were
      determined. Binding studies using the nonselective muscarinic antagonist
      [3H]quinuclidinyl benzilate, the M1-selective antagonist pirenzepine, and the M2
      selective antagonist AFDX-116 indicate that the receptors have the
      pharmacological properties of the cardiac (M2) receptor subtype. The receptors
      could be immunoprecipitated with a monoclonal antibody specific for the cardiac
      receptor, thus confirming the identity of the receptors expressed in these cells.
      The types of G proteins expressed in the cells were determined by Northern blot
      analyses: mRNA encoding the alpha subunits of Gs, G(o), and Gi-2, but not Gi-1 or
      Gi-3, were detected, consistent with previous observations of neonatal mammalian
      atria. The muscarinic receptors were functionally active, as demonstrated by the
      ability of the agonist to stimulate phosphoinositide turnover and to inhibit
      adenylyl cyclase activity. The availability of a mammalian atrial cell line that
      continues to express the appropriate functionally coupled subtype of muscarinic
      receptor may provide a useful system for the investigation of the regulation of
      expression and function of cardiac muscarinic receptors.

PMID- 8137512
TI  - Current methods for the measurement of growth hormone in urine.
AB  - Since the development of sensitive immunoassay procedures for the measurement of
      GH in urine, a urinary GH determination has been proposed as an alternative way
      of assessing pituitary GH secretion. Whilst studies on the clinical application
      of these assays have been difficult to correlate, for the reasons described, it
      is clear that an estimation of urinary GH has a useful role in clinical and
      physiological studies in both children and adults.

PMID- 8137513
TI  - Understanding the cause of idiopathic cranial diabetes insipidus: a step forward.

PMID- 8137514
TI  - Detection of vasopressin cell antibodies in some patients with autoimmune
      endocrine diseases without overt diabetes insipidus.
AB  - OBJECTIVE: Cytoplasmic autoantibodies to vasopressin cells (AVP) have been
      detected in patients with idiopathic central diabetes insipidus and only in one
      patient with endocrine autoimmune diseases without clinical diabetes insipidus.
      The aim of this study was to look for AVP cell antibodies (AVP-cell-Ab) in human
      sera of a large population of autoimmune endocrine disease patients without
      diabetes insipidus and to test whether an occurrence of these antibodies in some
      patients can be associated with partial impairment of posterior pituitary
      function. MEASUREMENT: Sera from 410 patients (310 females, 100 males, age range
      10-46 years) with autoimmune endocrine disorders (260 with thyroid autoimmune
      disease, and 150 with insulin dependent diabetes mellitus) without clinical
      diabetes insipidus, and from 100 normal subjects, were investigated for
      hypothalamic autoantibodies by an indirect immunofluorescence method. Positive
      sera were subsequently tested with specific rabbit anti AVP serum. RESULTS: None
      of controls, but five out of 410 patients (1.2%) were AVP-cell-Ab positive. All
      positive and nine negative from the 410 screened patients were tested for
      posterior pituitary function. Two out of five AVP-cell-Ab positive patients
      showed partial diabetes insipidus. CONCLUSION: AVP cell antibodies can be shown
      in some patients with endocrine autoimmune disease without diabetes insipidus and
      can sometimes be associated with findings of partial posterior pituitary
      dysfunction. This suggests that clinical diabetes insipidus could be preceded by
      a long subclinical period characterized only by the occurrence of AVP-cell-Ab in
      the sera associated or followed by alterations in functional tests. Longitudinal
      studies are needed to confirm this hypothesis.

PMID- 8137515
TI  - Prolactin, growth hormone and insulin-like growth factor-I in newborn children of
      smoking mothers.
AB  - OBJECTIVE: Since maternal smoking causes fetal circulatory abnormalities, as well
      as disturbances of the maternal endocrine equilibrium, we measured the PRL, hGH
      and insulin-like growth factor-I (IGF-I) concentrations in the cord and venous
      blood of neonates of smoking mothers to determine whether or not the tobacco
      smoke affects the endocrine status of the neonate. DESIGN: The above hormones
      were measured in the cord blood of the newborns of both smoking and non-smoking
      mothers. Also, PRL and hGH were determined at 24 and 72 hours after birth in
      newborns of both groups. PATIENTS: Fifty-three newborns of smoking and 47
      newborns of non-smoking mothers were investigated. Seventeen of the newborns of
      the smoking and 21 of the non-smoking mothers were preterm. The remainder were
      full-term. MEASUREMENTS: PRL was measured with a solid-phase immunoradiometric
      assay, hGH with a solid-phase two-site immunoradiometric assay and IGF-I with a
      solid-phase radioimmunoassay after extraction with acid-ethanol. RESULTS: The
      median value of PRL in the 17 preterm newborns of smoking mothers was 4941 mU/I
      (range 1322-7230), whereas in the 21 preterm newborns of non-smoking mothers it
      was 2013 mU/I (range 243-4740) (P = 0.0002). The median hGH value in the above
      subjects was 102.0 mU/I (range 35.2-208.4) and 59.8 mU/I (range 11.6-134.2),
      respectively (P = 0.0039). The median IGF-I was 580.7 U/I (range 253.2-4851.1)
      and 530.6 U/I (range 239.6-3591.5), respectively (P = 0.429). In the 36 full-term
      newborns of smoking mothers the median PRL value was 5171 mU/I (range 2074-7530),
      whereas in the 26 full-term newborns of non-smoking mothers it was 5081 (range
      244-6540) (P = 0.048). The median hGH was 69.6 mU/I (range 42.3-280.0) and 32.2
      mU/I (range 6.2-200.0), respectively (P = 0.0031). Also, the median IGF-I value
      was 926.3 U/I (range 348.5-5344.7) and 462.1 U/I (range 250.2-1578.7),
      respectively (P = 0.0024). On the 3rd day the PRL in the preterm neonates of both
      smoking and non-smoking mothers showed the same 16.5% drop, and thus the
      difference between the groups was maintained. A similar reduction in the hormone
      levels was observed in the full term neonates. CONCLUSIONS: The findings indicate
      that the maternal tobacco-smoking causes disturbances of the endocrine status of
      the fetus, as shown by the increased levels of PRL, hGH and IGF-I, which are more
      pronounced between 30 and 37 weeks of gestation than at term.

PMID- 8137517
TI  - Double blind randomized study using oral or injectable bromocriptine in patients
      with hyperprolactinaemia.
AB  - OBJECTIVE: A new long-acting injectable form of bromocriptine has become
      available for long-term treatment of hyperprolactinaemic patients. The objective
      of this study was to compare efficacy and tolerability of injectable and oral
      forms of bromocriptine. DESIGN: A double-blind randomized study. All patients
      received either one injection of bromocriptine 50 mg intramuscularly and placebo
      tablets for 28 days (Group A) or one placebo injection and oral bromocriptine 7.5
      mg daily for 28 days (Group B). PATIENTS: Twenty-three (12 patients for Group A
      and 11 patients for Group B) hyperprolactinaemia patients with (19 patients) or
      without (4 patients) CT/MRI evidence of tumour were studied. MEASUREMENTS: Plasma
      PRL levels and serum bromocriptine levels were assessed during a follow-up of 42
      days. MRI and/or CT were evaluated before and 28 days after the beginning of the
      study. RESULTS: All patients had significant reductions of PRL levels from 1000 h
      and 1100 h of day 1 to 2000 h of day 35. Normoprolactinaemia was shown in eight
      patients of Group A and six of Group B on days 1-28. Normal PRL levels were still
      present in five patients of Group A and in one patient of Group B on day 35; only
      three patients of Group A had normoprolactinaemia on day 42. A significantly
      greater decrease in Group A in comparison with Group B was shown at 1200 h on day
      1 and at all times as a percentage decrease from basal levels. Significantly
      higher levels of bromocriptine were shown in Group A at all timepoints studied.
      No difference was shown in tolerability and incidence of side-effects.
      CONCLUSION: Our data show that injectable bromocriptine more frequently induced a
      prolonged normoprolactinaemia than did the oral drug. Moreover, bromocriptine
      levels released during injectable bromocriptine were significantly higher than
      during oral bromocriptine. On the other hand no difference was shown in the
      tolerability of bromocriptine according to the route of administration.

PMID- 8137516
TI  - Acute effects of a single administration of dexamethasone on basal and growth
      hormone-releasing hormone stimulated GH secretion in acromegaly.
AB  - A single administration of dexamethasone causes both an early stimulatory and a
      late inhibitory effect on GH secretion in normal subjects. OBJECTIVE: We
      investigated the effects of a single administration of dexamethasone on basal and
      GH-releasing hormone-stimulated GH secretion in eight patients with active
      acromegaly. DESIGN: On three different days the patients received 4 mg i.v.
      dexamethasone, 1 microgram/kg body weight GH-releasing hormone 1-29, or matched
      placebos in different order. PATIENTS: Eight subjects with active acromegaly,
      five of whom had not been treated previously, while the other three had received
      octreotide therapy which was stopped at least 7 days before testing.
      MEASUREMENTS: Serum GH levels were measured in duplicate by a commercially
      available RIA kit. RESULTS: Dexamethasone administration caused a significant
      decline of mean +/- SE GH levels from 51.8 +/- 13.8 to 30.0 +/- 9.2 mU/I at 180
      minutes, that was not influenced by placebo administration at 180 minutes. On the
      contrary, when GH-releasing hormone substituted placebo administration, GH levels
      increased from 34.0 +/- 9.8 mU/I at 180 minutes to 56.0 +/- 15.6 mU/I at 195
      minutes. The GH increase was higher when GH-releasing hormone was given without
      dexamethasone pretreatment (from 52.4 +/- 13.0 mU/I at 180 minutes to 86.4 +/-
      25.4 mU/I at 195 minutes). Analysis of the GH area under the curve confirmed the
      significant inhibition of GH secretion after dexamethasone administration and the
      significant reduction of the GH response to GH-releasing hormone in the study
      with dexamethasone pretreatment. CONCLUSIONS: At variance with data in normal
      subjects, acute i.v. administration of dexamethasone inhibits basal GH secretion
      and partially suppresses the GH response to GH-releasing hormone in acromegaly.
      Both alterations in the regulatory mechanism of adenomatous cells and
      perturbations of hypothalamic regulatory influences, induced by the state of
      chronic GH hypersecretion, are likely explanations of the different response to
      dexamethasone.

PMID- 8137518
TI  - ACTH precursors characterize the ectopic ACTH syndrome.
AB  - OBJECTIVE: ACTH is secreted by the pituitary following processing of larger
      molecular weight precursors, proopiomelanocortin and pro-ACTH. Ectopic ACTH
      syndrome refers to the secretion of ACTH by non-pituitary tumours, but the
      predominant circulating form of proopiomelanocortin-related peptides remains
      unclear. PATIENTS: Fifteen patients with ectopic ACTH syndrome were compared to
      20 patients with pituitary-dependent Cushing's syndrome, 22 patients with small
      cell lung carcinoma but no evidence of Cushing's syndrome, and 25 controls.
      DESIGN AND MEASUREMENTS: Measurement of plasma ACTH and ACTH precursors using
      specific monoclonal-based immunoradiometric assays at 0900 h and, in five
      patients with ectopic ACTH syndrome, at 15-minute intervals for 6-24 hours.
      RESULTS: ACTH precursors were grossly elevated in patients with ectopic ACTH
      syndrome (median 2194, range 139-18000 pmol/l) compared to patients with
      Cushing's disease (median 33, 8-73 pmol/l, P < 0.001), patients with small cell
      lung carcinomas (38, 8-117 pmol/l, P < 0.001) and controls (26, 10-39 pmol/l, P <
      0.001). ACTH levels were also elevated in ectopic ACTH syndrome (0900 h median
      34, 11-152 pmol/l) compared to patients with Cushing's disease (0900 h median 8,
      3-19 pmol/l), but not to the same degree as ACTH precursors. In contrast with
      Cushing's disease, ACTH was secreted in a non-pulsatile fashion. ACTH precursors
      but not ACTH itself correlated with plasma cortisol in patients with ectopic ACTH
      syndrome (r = 0.65, P < 0.05). Chromatographic analysis of plasma from a patient
      with ectopic ACTH syndrome confirmed ACTH precursors and not ACTH to be the
      predominant circulating form. With the cross-reactivity of proopiomelanocortin
      and pro-ACTH in the ACTH IRMA of < 1 and < 10% respectively, ACTH precursors
      could represent all the ACTH immunoreactivity in patients with ectopic ACTH
      syndrome. CONCLUSIONS: Ectopic 'ACTH' is characterized by aberrant processing of
      proopiomelanocortin and should be more accurately referred to as 'ectopic ACTH
      precursor syndrome'.

PMID- 8137519
TI  - In-vitro evidence for the regulation of 17,20-lyase activity by cytochrome b5 in
      adrenocortical adenomas from patients with Cushing's syndrome.
AB  - OBJECTIVE: The electron transfer system molecules, NADPH-cytochrome P450
      reductase (Red) and cytochrome b5 (b5) are known to increase the relative
      activity of 17,20-lyase to 17 alpha-hydroxylase in vitro. Consistent with this
      hypothesis, we have reported recently that adrenocortical adenomas from patients
      with Cushing's syndrome that produced exceptionally high concentrations of
      androgens also contained more b5 mRNA as well as greater 17,20-lyase activity
      than adenomas that produced low concentrations of androgens. This finding was
      suggestive but inconclusive in linking b5 functionally to this difference in
      adenoma 17,20-lyase activity. In the present study, we have extended this finding
      by examining the effect of b5 on microsomal 17,20-lyase activity using an
      antibody against cytochrome b5. DESIGN: Biochemical quantitation of the content
      of b5 and Red activity in the microsomal fraction of the tumours and
      determination of 17,20-lyase activity in the microsomes in the presence or
      absence of an antibody against b5. PATIENTS: Seven patients with a clinical
      diagnosis of Cushing's syndrome secondary to benign adrenocortical adenoma were
      studied. MEASUREMENTS: The microsomal activities of 17 alpha-hydroxylase, 17,20
      lyase and 3 beta-hydroxysteroid dehydrogenase were measured by in-vitro enzyme
      assay with thin layer chromatography. Microsomal Red activity was assayed by
      measuring NADPH-dependent cytochrome c reduction reaction. Cytochrome b5
      concentration was determined by spectrophotometric analysis. RESULTS: An in-vitro
      enzyme assay of microsomal fractions from the adenoma showed that the 17,20-lyase
      activities of two adenomas that produced high concentrations of adrenal androgen
      were threefold greater than those of five other adenomas that produced low
      concentrations of androgens. Cytochrome b5 concentrations were greater in the two
      adenomas with high 17,20-lyase activity than in the other adenomas, while no
      significant difference in Red activity was observed among all the adenomas. The
      increased 17,20-lyase activity in the two adenomas was partially but
      significantly antagonized by an antibody against b5. CONCLUSIONS: These results
      suggest that differences in tissue b5 are functionally associated with
      differences in 17,20-lyase activity in adrenocortical adenomas in Cushing's
      syndrome, resulting in a dissociated secretion of cortisol and androgens in some
      patients.

PMID- 8137520
TI  - The neuroendocrine effects of sumatriptan, a specific ligand for 5-HT1-like
      receptors.
AB  - OBJECTIVE: A relationship between the serotoninergic and the opiatergic system in
      the pathogenesis of head pain is supported by several data. This study was
      carried out to investigate the neuroendocrine effects of sumatriptan, a specific
      serotonin agonist used in the treatment of migraine, on hypothalamic-pituitary
      adrenal axis (PHA) hormones. DESIGN: Two consecutive studies were performed. In
      study A, eight subjects received a subcutaneous (s.c.) injection of sumatriptan
      (6 mg). In study B, a further six subjects were randomized to receive either
      sumatriptan or placebo. SUBJECTS: Healthy volunteers recruited within the staff
      (eight males and six females) were studied. MEASUREMENT: In study A, plasma
      cortisol and PRL were measured by direct RIA and beta-endorphin after extraction
      and chromatography. Samples were collected from 60 minutes before to 120 minutes
      after the administration of the drug, at 15-minute intervals. According to the
      data of the first study, in study B, in addition to cortisol and beta-endorphin,
      ACTH was also measured. RESULTS: Significant increases in the mean beta-endorphin
      and cortisol concentrations were found in every subject receiving sumatriptan,
      while no significant changes were observed in prolactin plasma levels. Study B
      confirmed the activation of the pituitary-adrenal axis, additionally
      demonstrating the release of ACTH, and indicated that placebo has no effects.
      CONCLUSION: Acute s.c. stimulation with sumatriptan activates the pituitary
      adrenal axis.

PMID- 8137521
TI  - Gene screening in Japanese families with complete deficiency of thyroxine-binding
      globulin demonstrates that a nucleotide deletion at codon 352 may be a race
      specific mutation.
AB  - OBJECTIVE: Thyroxine-binding globulin (TBG) is a serum protein that transports
      75% of circulating thyroxine. Eleven naturally occurring mutations in the human
      TBG gene have been identified, ten of which alter the properties of the molecule.
      Three of these mutations produce complete deficiency of TBG (TBG-CD) and four are
      associated with a second mutation in codon 283 (TBG-poly) which is polymorphic in
      some ethnic groups but, when present alone, does not alter the properties of the
      TBG molecule. In this communication we investigate whether two unrelated Japanese
      families with TBG-CD harboured the TBG-CDJ mutation in codon 352 associated with
      TBG-CD in families residing in more distant locations of the Japanese Islands. In
      addition we examined the possible association with TBG-poly and its incidence in
      the Japanese population. DESIGN: Mutant alleles were identified by amplification
      of genomic DNAs by the polymerase chain reaction, using allele-specific
      oligonucleotide primers. PATIENTS: Eight family members and 25 normal subjects.
      MEASUREMENTS: Serum free thyroxine and TBG concentration were measured by a
      conventional radioimmunoassay and a more sensitive enzyme immunoassay. Genomic
      DNAs were extracted from white blood cells and specific mutations at codons 352
      and 283 were identified by allele-specific amplification. RESULTS: Three males
      and three females, whose serum TBG levels were decreased, had mutations at codon
      352 as hemizygous and heterozygous, respectively. This mutation was not present
      in the DNA of any of the related or unrelated subjects with normal TBG
      concentration. The presence of TBG-poly was demonstrated in only one heterozygous
      family member and in six out of 30 alleles (20%) in normal unrelated subjects.
      The frequency of this TBG polymorphism in the Japanese is similar to that of 16%
      reported in French Canadians. CONCLUSIONS: We conclude that TBG-CDJ might be a
      prevalent cause of complete deficiency of thyroxine-binding globulin in the
      Japanese and that TBG-poly probably appeared before the divergence of human
      races.

PMID- 8137522
TI  - Doppler echocardiographic evaluation of left ventricular diastolic function in
      acute hypothyroidism.
AB  - OBJECTIVE: Left ventricular diastolic dysfunction is an important cause of
      symptomatic heart failure. Previous studies suggest that thyroid dysfunction
      affects left ventricular diastolic function but the underlying mechanisms remain
      controversial. The study was undertaken to asses the influence of acute
      hypothyroidism on left ventricular diastolic function and to elucidate possible
      underlying mechanisms by means of Doppler echocardiography in a group of
      athyreotic patients, whose thyroid state depended only on external thyroid
      hormone supply and could therefore easily be controlled. PATIENTS: Eleven
      patients (5 men, 6 women, aged 20-55 years), who had had total thyroidectomy,
      were investigated during mild hyperthyroidism and during acute hypothyroidism.
      Additionally, 11 healthy control subjects aged 25-51 years were included in the
      study. DESIGN: M-mode echocardiography of the left ventricle and pulsed-wave
      Doppler echocardiography of the transmitral flow velocity pattern were carried
      out. RESULTS: Acute hypothyroidism produced a decrease of left ventricular end
      diastolic diameter from 48 +/- 5 to 46 +/- 5 mm (mean +/- SD P < 0.05), of peak
      velocity of early diastolic filling from 0.52 +/- 0.10 to 0.42 +/- 0.05 m/s (P <
      0.05), of peak velocity of late diastolic filling from 0.42 +/- 0.10 to 0.36 +/-
      0.09 m/s (P < 0.05), and a decreased time-velocity integral of early diastolic
      filling (6.2 +/- 1.8 vs 5.1 +/- 0.7 cm, P < 0.05). The other M-mode and Doppler
      echocardiographic parameters did not differ between the hyperthyroid and the
      hypothyroid states. CONCLUSIONS: The observed changes of the trans-mitral flow
      velocity pattern during acute hypothyroidism can be attributed to a reduction of
      pre-load. There is no direct evidence that acute hypothyroidism affects the
      intrinsic diastolic properties of the left ventricle.

PMID- 8137523
TI  - Alpha 2-adrenergic activity is normal in patients with thyroid disease.
AB  - OBJECTIVE: Several studies indicate an inverse relationship between the
      sympathetic nervous system activity and thyroid function. Altered adrenoceptor
      sensitivity, particularly alpha 1 and beta, have been described in hypothyroid
      and hyperthyroid patients. No information in patients with thyroid disease is
      available on the main mechanism regulating sympathetic nervous system outflow,
      i.e. the alpha 2-adrenoceptor pathway. In our study we evaluated alpha 2
      adrenergic activity in patients with thyroid disease by the assessment of
      cardiovascular and catecholamine response to clonidine, a central alpha 2
      adrenergic agonist. PATIENTS: Ten patients with hypothyroidism, six patients with
      hyperthyroidism before and during adequate therapy, and ten healthy subjects.
      MEASUREMENTS: After three blood samples for the basal determination of
      noradrenaline and adrenaline, the subjects swallowed 4 micrograms/kg body weight
      of clonidine. Blood pressure and pulse rate were measured 30, 60, 90, 120, 130
      and 140 minutes after clonidine administration; blood samples for determination
      of catecholamines were drawn at 120, 130 and 140 minutes. RESULTS: At
      presentation the decrease in plasma noradrenaline after clonidine in the patients
      was similar to that of the control group (hypothyroids: 1.07 +/- 0.23 nmol/l mean
      +/- SEM; hyperthyroids: 0.54 +/- 0.06 nmol/l; controls; 0.36 +/- 0.10 nmol/l; F =
      1.2, P = NS). No differences were detected in the fall in adrenaline and mean
      arterial pressure (MAP) after clonidine. The adequate therapy induced in
      hypothyroid patients a decrease in the basal levels of noradrenaline (1.88 +/-
      0.28 vs 0.67 +/- 0.10 nmol/l; P < 0.05) and a lesser fall in mean arterial
      pressure after clonidine (delta MAP 20.4 +/- 2.0 vs 9.7 +/- 2.8 mmHg; P < 0.05).
      No variations were detected in hyperthyroid patients after therapy either in
      basal hormones levels or in the magnitude of decrement in MAP and noradrenaline
      induced by clonidine. CONCLUSIONS: We conclude that in spite of the previously
      reported abnormalities in alpha 1 and beta-adrenergic receptor activity, the
      inhibitory alpha 2-receptor pathway is normal in patients with altered thyroid
      function.

PMID- 8137524
TI  - Sustained suppression of serum LH, FSH and testosterone and increase of high
      density lipoprotein cholesterol by daily injections of the GnRH antagonist
      cetrorelix over 8 days in normal men.
AB  - OBJECTIVE: Recently we have shown that single dose injections of the new GnRH
      antagonist cetrorelix ([Ac-D-Na(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala]GnRH;
      SB-75) decrease serum LH and testosterone in a dose-dependent manner in normal
      men. These results prompted us to investigate the effectiveness and safety of
      multiple daily injections of cetrorelix in normal male volunteers. DESIGN AND
      VOLUNTEERS: Following two control examinations 16 young men were randomly
      assigned to four study groups (n = 4/group). Daily doses of 0 (placebo), 2, 5,
      and 10 mg cetrorelix were injected subcutaneously at 0800 h for 8 days and
      morning and evening blood samples were obtained for 3 weeks. RESULTS: One day
      after the first cetrorelix injection, serum LH and testosterone concentrations
      were significantly suppressed in all treatment groups. Whereas in the 2 and 5-mg
      dose groups LH and testosterone showed some fluctuations, daily injections of 10
      mg cetrorelix consistently suppressed LH and testosterone in all men. In
      addition, in this group serum FSH concentrations were significantly suppressed to
      subnormal values 1 day after the first injection and remained in this range up to
      5 days after the last injection. A time and dose-dependent increase of high
      density lipoprotein cholesterol was observed during cetrorelix-induced
      testosterone deprivation with a maximal increase of 0.38 +/- 0.13 mmol/l (14.8 +/
      5.1 mg/dl; mean +/- SEM) in the 10-mg dose group. In addition, parallel to
      suppressed testosterone the volunteers' libido was significantly reduced under
      the GnRH antagonist. Apart from those symptoms caused by androgen deficiency, the
      only adverse side-effect observed was a mild painless local erythema at the
      injection site that disappeared within an hour. CONCLUSIONS: Daily injections of
      10 mg cetrorelix effectively and consistently suppress serum LH, FSH and
      testosterone concentrations, and therefore it has potential for treatment of sex
      hormone-dependent diseases and for male contraception.

PMID- 8137525
TI  - Prospective evaluation of insulin resistance and lipid metabolism in women
      receiving oral contraceptives.
AB  - OBJECTIVES: It has been suggested that normal women receiving oral contraceptives
      (OC) may develop a series of metabolic side-effects which relate to the risk of
      cardiovascular disease. These metabolic disturbances include changes in glucose
      and insulin metabolism, raised serum lipid and lipoprotein concentrations and
      elevated blood pressure. All these changes indicate that OC might cause insulin
      resistance. We have prospectively examined the effect of OC on insulin resistance
      and lipid metabolism including Lp(a) values. PATIENTS: The study group comprised
      13 normally menstruating Chinese women. DESIGN: The study subjects were given a
      combined triphasic oral contraceptive which was administered on a 21-day on, 7
      day off medication cyclic regimen, the first pill being administered on day 5
      from the beginning of menses. The metabolic investigations were carried out
      during luteal phase before OC and again the third week of the third month of OC
      administration. MEASUREMENTS: Metabolic evaluation including insulin secretion
      and insulin-mediated glucose uptake were evaluated by oral glucose tolerance test
      and the modification of insulin suppression test. Fasting triglyceride,
      cholesterol, HDL-cholesterol and Lp(a) concentrations were also measured.
      RESULTS: The plasma glucose and insulin responses during a 75-g oral glucose
      challenge increased significantly (P < 0.05 and P < 0.03, respectively). The
      steady-state plasma glucose (SSPG) concentrations achieved during constant
      infusion of glucose, insulin and somatostatin increased significantly after 3
      cycles of OC administration (glucose 7.5 +/- 0.8 vs 12.4 +/- 0.7 mmol/l, P <
      0.001) while the steady-state plasma insulin (SSPI) concentrations were
      relatively similar (410 +/- 14 vs 391 +/- 7 pmol/l, NS). Plasma triglyceride
      levels increased significantly (0.81 +/- 0.12 vs 1.09 +/- 0.19 mmol/l, P < 0.03)
      following OC administration. Fasting plasma cholesterol, HDL cholesterol and
      calculated LDL cholesterol concentrations did not change as compared with
      baseline values, nor did the ratio of total cholesterol to HDL cholesterol. The
      Lp(a) concentrations did not change during the administration of OC (81 +/- 25 vs
      71 +/- 21 mg/l, NS). CONCLUSIONS: These data indicated that intake of OC for 3
      cycles induced glucose intolerance, hyperinsulinaemia and insulin resistance in
      normal menstruating Chinese women. These changes occurred in association with
      elevated plasma triglyceride concentrations and no alteration in Lp(a) or other
      lipid values.

PMID- 8137526
TI  - Corticotrophin releasing hormone levels in human plasma and amniotic fluid during
      gestation.
AB  - OBJECTIVE: Corticotrophin releasing hormone, a hypothalamic neuropeptide also
      made in placenta, may regulate fetal maturation in a stress-responsive manner.
      The objectives of this study were: (1) to determine if levels of corticotrophin
      releasing hormone in the amniotic fluid correlate with fetal lung maturation; (2)
      to confirm that third trimester plasma levels of corticotrophin releasing hormone
      are increased in patients with pregnancy-induced hypertension compared to
      normotensives, and (3) to increase the recovery of extracted corticotrophin
      releasing hormone from plasma and amniotic fluid. DESIGN: (1) Levels of
      corticotrophin releasing hormone in amniotic fluid during the third trimester
      were compared with those of saturated phosphatidyl choline. (2) Corticotrophin
      releasing hormone levels were measured in a group of normotensive pregnant women
      during the entire gestation period. Corticotrophin releasing hormone levels
      during the third trimester were compared in normotensives and patients with
      pregnancy-induced hypertension. PATIENTS: Twenty-one non-pregnant normal
      volunteers and 63 pregnant women. MEASUREMENTS: Blood pressure, corticotrophin
      releasing hormone in plasma and amniotic fluid, and saturated phosphatidyl
      choline in amniotic fluid. RESULTS: Corticotrophin releasing hormone levels in
      amniotic fluid samples during the third trimester ranged from 12 to 98 pmol/l and
      positively correlated with the saturated phosphatidyl choline levels, but not
      with gestational age. A significant difference existed in plasma corticotrophin
      releasing hormone concentration between gestational age-matched third trimester
      normotensive and hypertensive gravids: corticotrophin releasing hormone levels
      were significantly lower in normotensives (223 +/- 65 pmol/l) than in patients
      with pregnancy-induced hypertension (544 +/- 106 pmol/l, P = 0.001). Plasma
      corticotrophin releasing hormone increased with gestational age from 51 pmol/l
      (range 8.4-85) at 25-32 weeks to 375 pmol/l (range 35-1386) at 33-40 weeks.
      During the third trimester the rise in plasma corticotrophin releasing hormone
      conformed to an exponential mathematical model of a positive feedback loop
      between placental corticotrophin releasing hormone and fetal adrenal cortisol.
      CONCLUSIONS: During the third trimester of pregnancy there is a positive
      correlation between the level of amniotic fluid corticotrophin releasing hormone
      and that of saturated phosphatidyl choline. The positive correlation between
      amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl
      choline, but not between amniotic fluid corticotrophin releasing hormone and
      gestational age, suggests that a factor(s), such as stress, may affect both
      amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl
      choline in parallel. Furthermore, our data are consistent with the hypothesis
      that the rise in placental corticotrophin releasing hormone is coupled to an
      increase in fetal glucocorticoid and lung maturation, and that stresses such as
      pregnancy-induced hypertension may accelerate this process.

PMID- 8137527
TI  - Longitudinal study of maternal plasma bioavailable testosterone and
      androstanediol glucuronide levels during pregnancy.
AB  - OBJECTIVE: The aim of this study to evaluate during normal pregnancy plasma
      bioavailable testosterone and androstanediol glucuronide levels. MEASUREMENTS:
      Bioavailable testosterone, androstanediol glucuronide and SHBG levels were
      evaluated every 4 weeks from week 6 to week 38 in 10 normal pregnant women. We
      also measured plasma oestradiol, oestriol, delta 4-androstenedione, 17
      hydroxyprogesterone, progesterone and testosterone. RESULTS: The mean
      bioavailable testosterone levels were within the range of non-pregnant women but
      with an increasing trend until delivery. Androstanediol glucuronide had increased
      at weeks 6 and 8, decreased at week 14, remained low at week 30, and increased
      again at week 34. SHBG was significantly correlated with testosterone, oestradiol
      and oestriol. No correlation could be established between androstanediol
      glucuronide and any other parameter. DISCUSSION: Bioavailable testosterone (non
      SHBG bound testosterone) represents the sum of free testosterone plus albumin
      bound testosterone. The increase in testosterone concentrations with decreased
      albumin levels during pregnancy, could suggest reduced metabolic clearance of
      testosterone throughout pregnancy. No correlation was established between the
      decrease in androstanediol glucuronide and increase in progesterone, suggesting
      that the decrease in androstanediol glucuronide is not a consequence of the
      inhibitory effect of progesterone on 5 alpha-reductase activity.

PMID- 8137528
TI  - Glucocorticoid responsive ACTH secreting bronchial carcinoid tumours contain high
      concentrations of glucocorticoid receptors.
AB  - Cushing's syndrome due to a bronchial ACTH secreting carcinoid tumour may be
      difficult to distinguish from a pituitary microadenoma (corticotrophinoma)
      causing Cushing's disease, since in both disorders ACTH secretion may be
      responsive to glucocorticoids. Why some bronchial carcinoid tumours are
      responsive is unknown but it could be because of co-secretion of corticotrophin
      releasing factor (CRF) and/or expression of glucocorticoid receptors. We report
      two patients with glucocorticoid responsive ACTH secreting bronchial carcinoid
      tumours, neither of whom produced or responded to CRF. Significant glucocorticoid
      receptor binding capacity (92 and 102 pmol/g protein), compared with control lung
      tissue, was found in extracts from both tumours. These findings suggest that
      corticotrophinoma-like responses to glucocorticoids observed in some ACTH
      secreting bronchial carcinoids result from expression of glucocorticoid receptors
      and are not necessarily related to the production of CRF.

PMID- 8137529
TI  - Multiple hormone production by pituitary tumours.

PMID- 8137530
TI  - Bone mineral density is decreased in hyperthyroidism.

PMID- 8137531
TI  - Use of pituitary function tests.

PMID- 8137532
TI  - Thyroid function tests are rarely abnormal in patients with severe hyperemesis
      gravidarum.

PMID- 8137533
TI  - Phototherapy--T cell vaccination by any other name?

PMID- 8137534
TI  - Photodynamic therapy; a comparison with other immunomodulatory treatments of
      adjuvant-enhanced arthritis in MRL-lpr mice.
AB  - Although numerous experimental immunomodulatory regimens have been reported to be
      effective in the treatment of rheumatoid arthritis, they also produce undesirable
      side effects. An alternative specific modality of localized treatment is
      photodynamic therapy (PDT). In this study we treated 13-week-old MRL-lpr mice
      whose spontaneous arthritis was enhanced by intradermal injection of Freund's
      complete adjuvant (FCA). One group received transcutaneous photodynamic therapy
      at days 0, 10, and 20, following the FCA injection. The other groups were
      injected with 1 mg/kg per day indomethacin, 40 mg/kg per day cyclosporin A (CsA),
      or treated with 3 Gy sublethal whole body irradiation (WBI). The development of
      swelling was monitored for 1 month, at which time proteinuria, lymphadenopathy
      and the histopathology of the joints and kidneys were assessed. The results
      demonstrated that PDT and the conventional treatments significantly ameliorated
      swelling of the hindlimbs from 70% in the untreated FCA-injected animals to below
      the 19% level characteristic of the unmanipulated control. Histological
      examination showed a reduction in pannus formation, and cartilage and bone
      destruction, the characteristics of adjuvant-enhanced arthritis. PDT did not
      affect the survival rate, lymphoproliferation, or proteinuria of the treated
      animals. However, indomethacin increased proteinuria, and was less effective in
      preventing cartilage and bone destruction. Furthermore, lower doses of CsA and
      WBI exacerbated arthritis activity. These results indicate that photodynamic
      therapy can inhibit the development of adjuvant-enhanced arthritis in MRL-lpr
      mice with similar effectiveness to the conventional treatments, but without their
      negative side effects.

PMID- 8137535
TI  - Characterization of an HLA-DR4-restricted T cell clone recognizing a protein
      moiety of small nuclear ribonucleoproteins (UsnRNP).
AB  - In sera of patients with mixed connective tissue disease (MCTD, Sharp Syndrome)
      high titres of IgG autoantibodies to U1snRNP-specific proteins are found. The
      isolated occurrence of these autoantibodies is highly associated with the HLA-DR4
      haplotype. snRNP-specific T cells are supposed to be involved in this
      autoantibody production. To address this question we cultured mononuclear cells
      from MCTD patients and healthy donors with a highly purified UsnRNP preparation
      from HeLa cells using bulk or limiting dilution cultures. Secondary responses to
      snRNP were detected only rarely with T cell lines from two patients and two
      controls, and turned out to be unstable during further expansion. One T cell line
      derived from a healthy individual retained its snRNP reactivity upon limiting
      dilution cloning and could be characterized in detail. The CD4+ T cell clone
      recognized native snRNP particles presented by monocytes in an HLA-DR4 (B1*0401)
      restricted manner. Separation of the protein and RNA moieties of snRNP particles
      revealed that the T cell clone responded specifically to the protein fraction,
      but not to RNA and diverse control antigens. Sequencing of the T cell receptor
      alpha and beta chain cDNAs revealed that the clone used the V alpha 14.2 and V
      beta 14 elements. Upon antigen-specific and mitogenic stimulation the T cell
      clone showed a Th1-specific cytokine pattern, and did not provide helper activity
      for in vitro immunoglobulin production. This study demonstrate the presence of
      self-reactive snRNP-specific T cells in a healthy donor. The T cell clone may not
      represent a helper T cell for the formation of U1snRNP-specific autoantibodies.

PMID- 8137536
TI  - Anti-5S RNA/protein (RNP) antibody levels correlate with disease activity in a
      patient with systemic lupus erythematosus (SLE) nephritis.
AB  - A patient with systemic lupus erythematosus (SLE) and nephritis without
      antibodies to dsDNA but with antibodies to a 5S RNA/protein (RNP) complex is
      presented. Combined RNA precipitation and Western blotting experiments strongly
      suggested that these newly identified autoantibodies recognized a distinct
      epitope on the L5 ribosomal protein of the L5/5S RNP complex first described by
      Steitz et al. [1]. Quantification of the anti-5S RNP antibody levels was done by
      hybridizing Northern blots of immunoprecipitated RNA from serial serum samples
      with a 32P-labelled oligoprobe specific for the 5S ribosomal RNA. These studies
      revealed a strong association between anti-5S RNP autoantibody titre and severity
      of SLE nephritis over a 3-year prospective study. Our results indicate that the
      L5/5S RNP can be a target of autoimmune response, and and may serve, in some
      cases, as marker of SLE severity and response to therapy.

PMID- 8137537
TI  - Epitope mapping of the 52-kD Ro/SSA autoantigen.
AB  - Autoantibodies to Ro/SSA are commonly found in sera of patients with systemic
      lupus erythematosus (SLE) and primary Sjogren's syndrome. The presence of these
      antibodies is related to lymphopenia, photosensitive dermatitis, and pulmonary
      and renal disease, suggesting that they have an immunopathologic role [1-6]. We
      previously isolated a cDNA clone which encodes the 52-kD human Ro/SSA protein. In
      this study we have determined the number and location of epitopes recognized by
      SLE sera using recombinant proteins encoded by the full-length or overlapping
      subclones of this cDNA. An immunodominant epitope was detected using Western
      blots and ELISA on the NH2-terminal side of this protein's putative leucine
      zipper. The data suggest that 11 amino acids are critical for the recognition of
      this molecule by these autoantibodies. Although the titres of anti-52-kD Ro/SSA
      antibodies vary between different patient sera, no heterogeneity in the location
      of antigenic epitopes to which their autoantibodies bound was detected. This
      homogeneous pattern of reactivity to a single rather than multiple regions of
      this protein is unusual for lupus autoantigens which have been identified, and
      suggests that these antibodies may have arisen as by a cross-reaction to an
      epitope on another molecule.

PMID- 8137538
TI  - Inhibition of histone/anti-histone reactivity by histone-binding serum
      components; differential effect on anti-H1 versus anti-H2B antibodies.
AB  - IgG fractions were purified on a protein G-agarose column from sera of both
      systemic lupus erythematosus (SLE) patients and healthy donors. All IgG
      fractions, after elution with 0.5 M acetic acid, reacted with histones in an anti
      histone ELISA assay, and IgG anti-histone activity was in all instances higher in
      the IgG fraction than in the corresponding whole serum. This was shown to be due
      to the presence in serum of histone-binding components that inhibited IgG binding
      to histones. Both normal human and SLE patients' sera had these histone-binding
      components, and disparity between serum-positive and -negative anti-histone
      antibody (AHA) tests was not dependent on differences in the blocking capacity
      but on IgG antibody levels and avidity. Interaction of normal serum IgG fraction
      with all five histones was of low avidity, whereas interaction of IgG from AHA
      positive SLE sera with both H1 and H2B had high avidity. Low-affinity antibodies
      to every histone fraction, but also high-affinity anti-H1 antibodies, were
      preferentially inhibited. Our data indicate that several serum protein components
      are inhibiting histone/anti-histone interaction and may play a protective role
      against both high-affinity anti-H1 antibodies present in SLE patients, and
      natural, low-affinity, anti-histone antibodies. As some acute phase proteins,
      notably C-reactive protein, bind to histones, it is conceivable that they play
      such a role. High-affinity anti-H2B antibodies, present in some SLE patients, and
      not inhibited by these serum components, may, on the other hand, participate in
      the pathogenesis of the disease.

PMID- 8137539
TI  - High-density proteoglycan induces specific suppression of adjuvant-induced
      arthritis in rats.
AB  - In vitro data support the view that T cells in adjuvant-induced arthritis (AIA)
      respond to the proteoglycan (PG) component of articular cartilage; however, an in
      vivo role for PG in AIA has yet to be shown. To do so, we examined the effects of
      pretreatment with bovine cartilage high density PG (HDPG) on AIA induced by heat
      killed Mycobacterium butyricum in Lewis rats. Purified bovine cartilage HDPG
      emulsified in Freund's incomplete adjuvant (FIA) was injected intradermally into
      rats 7 days before challenge with Myco. butyricum. The severity of arthritis was
      significantly suppressed in rats pretreated with as little as 0.75 mg of HDPG,
      and the arthritis was completely suppressed in rats pretreated with 3.0 mg of
      HDPG. This suppression was specific, as the same treatment did not protect
      against type II collagen-induced arthritis. Suppression of AIA is primarily a
      property of the HDPG, as suppression of the arthritis was significantly less with
      pretreatment with 3.0 mg of middle density fractions of PG, and no suppression
      was observed with pretreatment with the lowest density fraction of PG. Thus we
      report that pretreatment with cartilage HDPG, but not lower density PG, can
      induce specific suppression of AIA. These in vivo results support the view that
      immunity to cartilage HDPG plays a major role in the pathogenesis of AIA, and can
      induce specific tolerance to this type of arthritis.

PMID- 8137540
TI  - Abnormalities in subset distribution, activation, and differentiation of T cells
      isolated from large intestine biopsies in HIV infection. The Berlin
      Diarrhoea/Wasting Syndrome Study Group.
AB  - Intestinal T cells have a unique state of activation and differentiation which
      might specifically affect or be affected by HIV infection. Lymphocyte subsets in
      the peripheral blood are well characterized, but our knowledge about intestinal
      lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes
      isolated from large intestine biopsies of AIDS patients and controls by three
      colour cytofluorometry. In the large intestine of HIV-infected patients CD4 T
      cells were reduced and CD8 T cells were increased compared with controls. Most of
      the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxic
      phenotype. Activated and resting CD4 T cells were similarly reduced, the
      expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased,
      respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but
      the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased
      expression of all these differentiation markers. Our findings demonstrate
      substantial alterations in subset distribution, activation, and differentiation
      of large intestine T cells, which may contribute to the secondary infections and
      malignancies commonly observed in the gut of AIDS patients.

PMID- 8137541
TI  - Antigenic cross-reactivity between human T lymphotropic virus type I (HTLV-I) and
      retinal antigens recognized by T cells.
AB  - To investigate the relationship between uveitis and HTLV-I infection, we examined
      the cross-reactivity between HTLV-I antigens and retinal antigens recognized by T
      cells in B10.BR mice immunized with human HTLV-I-infected MT-2 cells. We found
      that T cells obtained from MT-2 immune mouse spleen responded not only to HTLV-I
      antigens but also to retinal antigens of various species. However, they did not
      respond to HTLV-I-negative lymphoid cell lines. Furthermore, established T cell
      lines from MT-2 immune spleen cells also responded to both HTLV-I and retinal
      antigens. The phenotype of the immune cells that responded to both HTLV-I and
      retinal antigens was CD4+, CD8-, and CD3+. The proliferative response of T cell
      lines to HTLV-I as well as various retinal antigens, was clearly blocked by
      addition of anti-CD3, anti-CD4, or anti-I-Ak MoAbs, but not by anti-CD8 antibody.
      The established T cell lines from HTLV-I immune spleen cells were all found to be
      CD3+, TCR beta +, CD4+, CD8- cells by flow cytometric analysis. These results
      indicate that an epitope of HTLV-I antigens is cross-reactive to an epitope of
      retinal antigens extracted from either human retinoblastoma or normal murine,
      rat, and bovine retinae at a T cell recognition level.

PMID- 8137542
TI  - H-2b restriction of the immune response to the p126 Plasmodium falciparum
      antigen.
AB  - Inbred BALB/c (H-2d), CBA (H-2k) and C57B1/6 (H-2b) mice immunized with
      Plasmodium falciparum schizonts or culture supernates develop antibodies of
      different antigenic specificities. It has been observed that C57B1/6 mice were
      unable to produce detectable antibodies against the p126 antigen (native molecule
      and p73 or p50 processed fragments) compared with other inbred mice. Similar
      results were obtained using BALB congenic mice with a lack of p126 antibody
      response in H-2b mice, while H-2d and H-2k mice produced antibodies against the
      p126. Lymphocyte proliferation assays performed by incubation of spleen cells
      with immunopurified p126 were positive for immunized BALB/c (H-2d) and congenic H
      2d or H-2k mice. On the other hand, no lymphocyte stimulation was observed with
      either C57B1/6 (H-2b) or congenic H-2b mice. These results suggest an MHC
      restriction of the immune response against the entire p126 (found in schizonts)
      and its p73 and p50 naturally processed fragments (found in culture supernates).

PMID- 8137543
TI  - Antimicrobial action of antibodies against Giardia muris trophozoites.
AB  - The activities of immune serum and trophozoite-specific MoAb were examined in
      vitro and in vivo. Immune serum and anti-Giardia muris MoAb caused immobilization
      of the trophozoites in vitro and were cytotoxic for trophozoites in the presence
      of exogenous complement. Both immune serum obtained from experimentally infected
      mice and anti-G. muris MoAb administered directly into the duodenum of mice
      significantly reduced the number of trophozoites in the small intestine during
      the acute phase of the infection. These results suggest that serum antibodies
      play a central role in the elimination of the primary Giardia infection.

PMID- 8137545
TI  - Serial functional affinity of autoantibodies in anti-glomerular basement membrane
      disease.
AB  - Anti-glomerular basement membrane (GBM) disease is caused by an autoantibody
      directed against an epitope on the alpha 3 chain of type IV collagen. Animal
      models demonstrate that the higher the affinity of such antibodies, the greater
      the degree of glomerular injury. Affinity maturation (the process whereby somatic
      mutation followed by antigen selection leads to an increase in affinity of
      antibody) might therefore be of pathogenic significance if it occurs in human
      anti-GBM disease. We have examined serial samples from nine patients with anti
      GBM disease and looked for evidence of changing functional affinity by measuring
      the inhibition of binding produced by the mild chaotrope diethylamine (DEA) in an
      anti-GBM antibody ELISA. Seven patients showed no change in the inhibition
      produced by DEA with time. Two patients showed an apparent decrease with time in
      the inhibition produced by DEA; this apparent increase in functional affinity
      proved, on further investigation, to represent simply the loss of anti-GBM
      antibodies. These results may imply that affinity maturation has been completed
      by the time that patients present with anti-GBM disease. If there had been
      evidence for a further increase in functional affinity after this point then this
      might have added extra urgency to the need for removal of these autoantibodies as
      part of treatment.

PMID- 8137544
TI  - Anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease:
      characterization and clinical correlates.
AB  - ANCA were detected by indirect immunofluorescence in 34 out of 67 patients with
      ulcerative colitis (UC, 51%) and in 14 out of 35 patients with Crohn's disease
      (CD, 40%). All but one ANCA-positive sera produced a perinuclear pattern of
      fluorescence (P-ANCA) on ethanol-fixed neutrophils. On paraformaldehyde-fixed
      neutrophils 76% of P-ANCA-positive sera in UC and 50% of P-ANCA-positive sera in
      CD produced cytoplasmic fluorescence, indicating that, indeed, cytoplasmic
      antigens are recognized by a considerable number of these sera. By Western blot
      analysis using whole neutrophil extract as a substrate 46% of sera from patients
      with UC and 32% of sera from patients with CD showed reactivity with either
      lactoferrin, polypeptides occurring as a doublet of 66/67 kD mol. wt, or
      polypeptides occurring as a doublet of 63/54 kD mol. wt, respectively. Identical
      patterns of reactivity have been observed among P-ANCA-positive sera from
      patients with autoimmune liver disease and rheumatoid arthritis. These data
      suggest that ANCA of restricted specificities are not specific for inflammatory
      bowel disease (IBD), but are present in diverse conditions characterized by
      chronic idiopathic inflammation.

PMID- 8137546
TI  - Suppression of pulmonary injury in experimental 'Goodpasture's syndrome' by
      deoxyspergualin (DSP).
AB  - DSP is a potent immunosuppressive drug which can prevent allograft rejection and
      suppress acute rejection episodes. In this study, the ability of DSP to suppress
      pulmonary injury in experimental Goodpasture's syndrome was investigated. Passive
      accelerated anti-glomerular basement membrane (GBM) disease was induced in rats
      by priming with rabbit IgG, followed 5 days later by injection of rabbit anti-GBM
      serum (day 0). Groups of five animals were treated with DSP (5 mg/kg
      intraperitoneally per day) or saline (untreated) from day 0 until being killed on
      days 1, 7, 14 or 21. At day 1, both DSP-treated and untreated animals exhibited
      similar pulmonary haemorrhage, oedema, and prominent perivascular leucocyte
      infiltration. Untreated animals subsequently developed severe widespread
      pulmonary damage including granulomatous lesions and extensive fibrosis, which
      correlated with infiltration of macrophages and immune-activated (IL-2R+)
      mononuclear cells (P < 0.01). Tumour necrosis factor-alpha (TNF-alpha), a known
      mediator of acute lung damage, was produced by pulmonary mononuclear cells
      throughout the experimental course. In contrast, DSP treatment resolved pulmonary
      haemorrhage, prevented the appearance of granulomatous lesions, and resulted in a
      histologically normal lung structure by day 21. This improvement was associated
      with a marked suppression of macrophage infiltration (P < 0.001 versus
      untreated), accumulation of immune activated (IL-2R+) mononuclear cells (P < 0.01
      versus untreated), and TNF-alpha production (P < 0.05 versus untreated). DSP
      treatment also suppressed the deposition of rat anti-rabbit IgG immunoglobulin
      and C3 along the alveolar basement membrane (P < 0.05 versus untreated). In
      conclusion, DSP suppressed pulmonary injury in accelerated anti-GBM disease by
      acting on the local cellular immune response and the systemic humoral immune
      response. Further studies are warranted to determine whether this could be a
      useful drug for the treatment of Goodpasture's syndrome in humans.

PMID- 8137547
TI  - Increased CD45RO expression on T lymphocytes in mediastinal lymph node and
      pulmonary lesions of patients with pulmonary sarcoidosis.
AB  - Sarcoidosis is characterized by a cell-mediated response mediated by the
      activation of CD4+ T lymphocytes in an environment lacking adequate numbers of
      regulatory CD8+ T lymphocytes. Immunohistological studies on frozen tissues have
      shown that sarcoid lesions have activated CD4 helper/inducer T lymphocytes at the
      centre of granulomata, whereas lymphocytes at the periphery are mainly CD8
      suppressor/cytotoxic cells. In this study we investigated the immunohistological
      distribution of CD45 isoforms of T cells in 29 paraffin-embedded sarcoid lesions
      in mediastinal and open lung biopsies. Ten of these were assessed quantitatively,
      with single-staining of serial sections demonstrating a predominance of CD45RO
      memory T lymphocytes in granulomata and intergranulomatous areas. Ratios of
      CD45RO:CD45RA T lymphocytes (or the ratio of memory to naive T cells) were 42.0:1
      for granulomata and 17.9:1 for intergranulomatous areas of sarcoid lesions
      counted. This finding is compatible with the hypothesis that nearly all the
      lymphocytes present in sarcoid lesions have been previously activated, and
      selectively home to sarcoid lesions.

PMID- 8137548
TI  - Immunosuppressive activity of bromocriptine on human T lymphocyte function in
      vitro.
AB  - Bromocriptine (BRC), a dopamine type 2 agonist, prevents secretion of pituitary
      prolactin (PRL). BRC has been shown to impair lymphocyte responsiveness toward
      antigenic stimulation by decreasing serum PRL levels. Hypoprolactinaemia induced
      by BRC produces a similar immunosuppressive effect, as observed in
      hypophysectomized rats, which is restored by the administration of PRL.
      Therefore, the immunosuppression induced by BRC has been interpreted as the
      result of hypoprolactinaemia. However, the direct mechanism of BRC in immune
      response has never been evoked. We recently reported that BRC has an
      immunosuppressive activity on human B lymphocyte function in vitro. In the
      present study we demonstrate that BRC suppresses T cell proliferation by means of
      blocking IL-2 production by T cells as well as mixed lymphocyte reaction (MLR) in
      a dose-dependent manner. We could not detect the immunoreactive PRL activity in
      the conditioned medium from polyclonal T cell mitogen-stimulated T cell cultures.
      Then, the immunosuppressive activity of BRC on human T cell function appeared to
      be independent of its hypoprolactinaemic effect. Treatment with low-dose
      cyclosporin A (CsA) or FK506 in combination with BRC has proved more effective
      than either drug alone in suppression of T cell proliferation and CD25 antigen
      expression. Thus, the therapeutic application of BRC in combination with
      immunosuppressants may enhance the immunosuppressive effect, while at the same
      time decreasing the toxicity.

PMID- 8137549
TI  - Increased cyclosporine sensitivity of T cells from cord blood compared with those
      from the adult.
AB  - Despite the increasing numbers of paediatric transplants performed, little is
      known about the immune responses of T lymphocytes in human neonates. Here we have
      compared the effects of cyclosporine on the phytohaemagglutinin (PHA) response of
      immature (cord) and mature (adult) lymphocytes using the following parameters of
      activation: (i) proliferation, measured by 3H-thymidine uptake; (ii) expression
      of cell surface IL-2 receptor; (iii) release of IL-2 into the supernatant.
      Cyclosporine was added to cultures of PHA-stimulated lymphocytes at doses ranging
      from 5 to 5000 ng/ml. The proliferative response of cord lymphocytes was
      considerably more sensitive to cyclosporine at each dose, so that 50% inhibition
      was achieved by 6 ng/ml and 21.5 ng/ml doses of cyclosporine on cord and adult
      lymphocytes, respectively. Expression of the IL-2 receptor by PHA-activated T
      cells and their subsets was assessed by flow cytometry. Cyclosporine inhibited IL
      2 receptor expression to a significantly greater degree in cord CD4 and CD8 cells
      (49.7% and 70.1%) than in adults (17.9% and 30.0%). Biologically active IL-2
      release was measured using the IL-2-dependent cell line CTLL-2. Cyclosporine at
      doses 50-5000 ng/ml produced 80-99% inhibition of both cord and adult responses.
      However, at very low doses (5 ng/ml) cyclosporine produced 69.3% inhibition of
      cord lymphocytes, compared with 42.0% of adult lymphocytes. These results suggest
      that the T cells of neonates are considerably more sensitive to cyclosporine than
      are adult T cells.

PMID- 8137550
TI  - Induction of autoimmune disease by graft-versus-host reaction across MHC class II
      difference: modification of the lesions in IL-6 transgenic mice.
AB  - We examined the effect of IL-6 on the development of autoimmune diseases (primary
      biliary cirrhosis, Sjogren's syndrome) employing murine graft-versus-host
      reaction (GVHR) model with MHC class II disparity. For this purpose, we used IL-6
      transgenic (B6.6) mice in which a high level of IL-6 was detected. C57Bl/6 (B6)
      spleen T cells were injected into B6.6 mated with B6.C-H-2bm12 (bm12) mutant mice
      ((bm12 x B6.6)F1) and GVHR with MHC class II disparity was induced. The
      transgenic hybrid mice with GVHR showed a larger spleen index and contained a
      higher serum level of IL-6 than those without GVHR. Autoimmune-like lesions in
      transgenic recipients became weakened compared with those in non-transgenic (bm12
      x B6)F1 recipients. In contrast, levels of antimitochondrial antibodies in (bm12
      x B6.6)F1 GVHR group were significantly higher than that of (bm12 x B6)F1 GVHR
      group. These results indicate that IL-6 excessively produced in vivo might
      regulate the progression of autoimmune diseases.

PMID- 8137551
TI  - IL-6 induces hepatic inflammation and collagen synthesis in vivo.
AB  - IL-6 regulates the synthesis of a broad spectrum of acute phase proteins in the
      liver. Also, it is involved in the pathogenesis of many fibrogenic diseases. To
      study the inflammatory effects of IL-6 on the liver in vivo, human rIL-6,
      produced in Escherichia coli, was injected intraperitoneally into rats (25
      micrograms/100 g body weight). The major fraction of injected IL-6 was
      accumulated in the liver within 40 min, and the number of platelets was increased
      during 72 h after injection. After 5 weeks of injection, the levels of serum
      glutamine pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT)
      were not changed, but they were significantly elevated at 13 weeks of treatment.
      Meanwhile, serum albumin levels were slightly decreased compared with those of
      controls. The same phenomena were observed in carbon tetrachloride-treated rats.
      Collagen synthesis was increased in the liver tissues and in the culture
      supernatants of hepatic lipocytes isolated from the rats treated with IL-6 for 13
      weeks. Histological analysis correlated well with biochemical analysis. At 5
      weeks of treatment, only mild pathological changes were observed, but severe
      hepatocyte necrosis and the accumulation of fibres in necrotic area were
      developed in the liver of IL-6-treated rats after 13 weeks of treatment,
      confirming that hepatic inflammation and fibrosis were developed. IL-6 activities
      in the sera and in the culture supernatants of lipocytes from IL-6-treated rats
      were elevated compared with those in controls. These biochemical and pathological
      data indicate that IL-6 can induce hepatic inflammation, and it has important
      roles in the pathogenesis of fibrosis and diseases of the liver in vivo. In
      addition, these results will provide useful information for the clinical trials
      of IL-6.

PMID- 8137552
TI  - Constitutive c-fos expression in osteoblastic MC3T3-E1 cells stimulates
      osteoclast maturation and osteoclastic bone resorption.
AB  - The effect of culture supernatants of c-fos-transfected MC3T3-E1 osteoblastic
      cells on osteoclastic bone resorption was studied. Human c-fos cDNA was
      integrated in the expression vector pH8, and the cells were transfected using the
      calcium phosphate precipitation technique. Osteoclastic bone resorption was
      quantified by the pit formation assay, and the osteoclast maturation from
      precursor was assessed by the generation of tartrate-resistant acid phosphatase
      (TRAP)-positive multinucleated cells (MNC). The culture supernatants of MC3T3-E1
      transfectants constitutively expressing c-fos gene enhanced osteoclast-like MNC
      formation from haematopoietic blast cells compared with those of control
      transfectants (P < 0.01). The culture supernatants also promoted osteoclastic
      bone resorption: the pit number, 118.7 +/- 38.5, was significantly higher than
      19.0 +/- 10.1 of the control (P < 0.05). The absorption area, 12,394 +/- 3145
      mm2, was significantly larger than 1646 +/- 314 mm2 of the control (P < 0.05).
      The culture supernatants also promoted bone resorption by purified chick
      osteoclasts (P < 0.05). The results show that constitutive expression of c-fos
      gene in osteoblastic MC3T3-E1 cells stimulates osteoclast maturation and
      osteoclastic bone resorption by releasing humoral mediator(s).

PMID- 8137553
TI  - Interferon-gamma enhances monoclonal antibody 17-1A-dependent neutrophil
      cytotoxicity toward colorectal carcinoma cell line SW11-16.
AB  - 17-1A is a murine monoclonal antibody (MAb) specific for the tumor-associated
      antigen CO17-1A on colorectal carcinoma cells. One of the tumor cell destruction
      mechanisms induced by in vivo immunotherapy with MAb17-1A has been claimed to be
      antibody-dependent cellular cytotoxicity (ADCC) by monocytes and NK cells. In the
      present study we investigated whether human neutrophils (PMN) could be involved
      in colorectal carcinoma cell lysis and whether IFN-gamma influences this
      function. We showed that neutrophils are capable of tumor lysis mediated by MAb17
      1A, although to a lesser extent than are the mononuclear cells (PBMC). Neutrophil
      ADCC was, however, markedly increased in the presence of IFN-gamma. Enhancement
      by IFN-gamma was also observed for PBMC. ADCC by PMN required the binding of
      MAb17-1A to Fc gamma RIII (CD16) since anti-Fc gamma RIII MAbs efficiently
      blocked tumor cell lysis. In contrast, in the presence of IFN-gamma the
      neutralization of Fc gamma RIII did not affect MAb17-1A-mediated cytotoxicity,
      suggesting that receptors other than Fc gamma RIII were involved in the process.
      PBMC cytotoxicity was also inhibited by anti-CD16 antibodies but IFN-gamma did
      not overcome this effect. Finally, the scavenger enzymes superoxide dismutase and
      catalase did not block ADCC by PMN or PBMC, indicating that oxidants are not key
      factors in MAb17-1A-mediated lysis; however, in IFN-gamma-activated PMN the
      oxygen-dependent mechanism was in part involved in tumor lysis.

PMID- 8137554
TI  - TSH and TSH receptor antibody-binding sites in fibroblasts of pretibial myxedema
      are related to the extracellular domain of entire TSH receptor.
AB  - The role of TSH receptor antibodies in the pathogenesis of pretibial myxedema is
      still unclear. This study was designed to determine whether patients with
      pretibial myxedema had higher serum titers of TSH receptor antibodies, and
      whether there were TSH and TSH receptor antibody-binding sites on plasma
      membranes of fibroblasts derived from the skin of pretibial myxedema. If there
      were, were the binding sites similar to the TSH receptor? The TSH receptor
      antibodies were determined with radioreceptor assay in 20 normal subjects, 18
      hyperthyroid Graves' disease patients without ophthalmopathy, 26 hyperthyroid
      Graves' disease patients with ophthalmopathy, and 11 patients with pretibial
      myxedema associated with Graves' ophthalmopathy. TSH and TSH receptor antibody
      binding sites were studied on plasma membranes of fibroblasts cultured from the
      skin of pretibial myxedema with radioreceptor assay. RNA was also extracted from
      the fibroblasts of pretibial myxedema and reverse transcribed using random
      primers as the primers for cDNA synthesis. The resulting cDNAs were subjected to
      amplification by polymerase chain reaction with the use of a set of primers
      spanning the 5' region (+256/+275 and +616/+635) and the 3' region (+1819/+1838
      and +2405/+2424) of the TSH receptor cDNA (+1 transcription start codon). They
      were further identified by Southern blot hybridization, with the probe spanning
      the 5' region (+272/+612) and the 3' region (+1908/+2268) of the TSH receptor
      cDNA (+ 1 transcription start codon), and sequencing. The results showed that
      patients with pretibial myxedema had higher titers of TSH receptor antibodies in
      the serum. TSH and TSH receptor antibody-binding sites were present on plasma
      membranes of fibroblasts derived from the skin of pretibial myxedema patients and
      related to the extracellular domain of the TSH receptor. These data suggest a
      common antigenic site in the skin and in the thyroid as a putative target for TSH
      receptor antibodies or lymphocytes of Graves' disease.

PMID- 8137555
TI  - Use of a flow cytometric assay to quantitate apoptosis in human lymphocytes.
AB  - Apoptosis is an active process of cellular self-destruction which plays an
      important physiologic role in the maintenance of homeostasis. This form of cell
      death has classically been assessed by the appearance of a "ladder-like" banding
      pattern upon gel electrophoresis of disrupted cells. The electrophoretic method
      is qualitative but offers no means of quantitation. We have optimized a flow
      cytometric method which allows quantitation of the apoptotic subset of cells.
      This assay uses propidium iodide and therefore can be performed on any flow
      cytometer with a blue-green excitation line. We initially verified the results of
      this method by using human thymocytes treated with dexamethasone, a known inducer
      of apoptosis. Gels were run simultaneously with flow cytometric analysis and
      assessed for the presence or the absence of apoptotic cells. Results obtained
      with gel electrophoresis correlated well with the flow cytometric method. In
      further studies, we applied this assay to human PBMC and obtained similar
      results. In conclusion, this assay is a significant improvement over currently
      available methodology for the determination of apoptosis. We have found it to be
      quantitative, reproducible, and applicable to different human cell types. The
      role of apoptosis in human disease remains to be elucidated and this method
      offers a convenient means to study this process.

PMID- 8137556
TI  - The development of the immune system--importance in the ascertainment of
      immunophenotypic changes in perinatal HIV infection.
AB  - Evidence is presented that the percentage and number of some subsets of T and B
      cells in normal children and adults vary greatly from those in fetal life and
      throughout the first few years after birth, and less so during adolescence and
      adulthood. Depending then on the age at which immunological studies are
      performed, as well as whether the HIV infection occurs in utero, at birth, or
      postnatally, values obtained by immunophenotypic analyses of differentiating or
      mature immunocytes will vary greatly. A concerted effort needs to be made to
      measure different developmental and activation immunophenotypic markers, from
      birth on, in premature and full-term infants of varying socioeconomic and ethnic
      background. Results from such studies should improve our ability to determine the
      timing of HIV infection, to obtain earlier guidelines for prophylaxis or
      treatment of the virus or of opportunistic infections, as well as to improve
      prognostic capabilities in perinatal HIV infection.

PMID- 8137557
TI  - Soluble CD23 and interleukin-4 levels in autoimmune chronic active hepatitis and
      systemic lupus erythematosus.
AB  - A variety of cytokines secreted by cells of the immune system could contribute to
      the induction or persistence of the inflammatory processes in autoimmune and
      infectious diseases. Soluble CD23 (sCD23) and interleukin-4 (IL-4) are the
      recently characterized factors implicated in B cell-T cell function in human
      disease. In this study we examined the circulating levels of sCD23, IL-4, and
      soluble interleukin-2 receptors (sIL-2R) from patients with hepatitis B surface
      antigen-positive (HBsAg+) acute viral hepatitis (AVH), HBsAg+ chronic active
      hepatitis (HBsAg+ CAH), and autoimmune chronic active hepatitis (AICAH) and from
      autoimmune rheumatic disease patients, such as systemic lupus erythematosus (SLE)
      and rheumatoid arthritis (RA). The sCD23 was found in sera from 16 of 16 patients
      with AICAH (159.0 +/- 40.8 ng/ml), in 3 of 32 patients with AVH (4.1 +/- 15.6), 5
      of 30 patients with HBsAg+ CAH (6.9 +/- 17), 8 of 25 patients with SLE (19.4 +/-
      37.2), 2 of 21 patients with RA (4.7 +/- 16.3), and none of the 50 age-matched
      healthy controls. However, sIL-2R was detected more frequently in sera from all
      hepatitis and rheumatic disease patients. In AICAH, sCD23 levels correlated
      positively with IL-4 (r = 0.44, P = 0.001) but not with sIL-2R. Markedly elevated
      levels of sCD23 and IL-4 in serum are prominent and characteristic features of
      AICAH disease, which could play an important role in the pathogenesis or
      induction and perpetuation of the inflammatory response in this disorder.

PMID- 8137558
TI  - Thymic hypoplasia and T-cell deficiency in ectodermal dysplasia: case report and
      review of the literature.
AB  - Ectodermal dysplasia is a heterogeneous disorder that includes a constellation of
      congenital malformations occasionally associated with mild to moderate immune
      dysfunction. In this report, we describe a female infant with ectodermal
      dysplasia who was found to have thymic hypoplasia but no other phenotypic
      features of the DiGeorge anomalad. She experienced Candida parapsilosis sepsis at
      1 week of age and a skin infection with Mycobacterium chelonii at 6 months. The
      numbers of blood B cells were normal and serum immunoglobulins normal to slightly
      reduced, but serum antibody responses of all immunoglobulin isotypes to protein
      immunogens were absent. Blood T cells were profoundly reduced and proliferative
      responses of T cells to mitogens were blunted. In contrast, there was an
      increased number of natural killer (NK) cells and increased NK activity in the
      blood. Over the first year of life, some of the immunodeficiencies resolved.
      Although the numbers of blood T cells (17% of total lymphocytes) remained low,
      proliferative responses to mitogens normalized and specific antibody responses
      improved. It seems likely that the thymic hypoplasia in this case was due to a
      paucity of ectodermal elements in the developing thymus, and that the immune
      defects were largely secondary to that event. In that respect, this human model
      of ectodermal dysplasia and thymic hypoplasia resembled the ectodermal/thymic
      defects found in the nude mouse.

PMID- 8137559
TI  - The interleukin-2 receptor subunit expression and function on peripheral blood
      lymphocytes from HIV-infected and control persons.
AB  - The expression of interleukin-2 receptor (IL2R) was studied on circulating
      lymphocytes from HIV-infected (HIV+) and control subjects, using chain-specific
      monoclonal antibodies and indirect immunofluorescence flow cytometry. The IL2R
      alpha chain expression was decreased on CD4 and CD8 T cells from HIV+ persons
      compared to controls. Conversely, beta chain expression was enhanced on both T
      cell subsets from the patients. IL2R-subunit levels were similar on natural
      killer cells from patients and controls. To evaluate the function of IL2R, we
      investigated to what extent IL2 could induce CD69, an early activation marker of
      lymphocytes. A dose-dependent increase of CD69 expression was observed on T and
      NK cells from all subjects. The upregulation of CD69 was similar on CD4 T and NK
      cells from patients and controls, but was more pronounced on CD8 T cells from
      HIV+ compared to HIV- subjects. Based on inhibition studies, both the alpha and
      the beta chain contributed to the IL-2-induced CD69 expression on CD4 T cells,
      pointing to involvement of the high-affinity receptor. The early activation of
      CD8 T cells and NK cells was mainly dependent on the intermediate-affinity
      receptor. We conclude that significant changes in IL2R alpha and beta chain
      expression on circulating T cells occur after HIV infection, but that early
      activation through IL2 is preserved or enhanced, even in advanced stages.

PMID- 8137560
TI  - High frequency of B cells capable of producing anti-thyrotropin receptor
      antibodies in patients with Graves' disease.
AB  - Hyperthyroidism in Graves' disease (GD) is mediated by antibodies to the
      thyrotropin receptor (TSHr). Patients that go into remission show a decline in
      antibody titer. However, upon cessation of treatment with anti-thyroid drugs a
      significant proportion of patients relapse and TSHr antibodies (TSHrAb) are
      present in their circulation. This suggests that B cells capable of producing
      TSHrAb persist despite treatment. To determine the frequency of these cells, B
      cells from six patients with GD and four healthy controls were infected with
      Epstein-Barr virus and cultured in 96-well plates at varying cell concentrations.
      A higher frequency of B cells capable of producing TSHrAbs was detected in
      patients with GD, relative to normal controls. For example, at 2 x 10(5) cells
      per well, 100% of wells containing cells from either patients with GD or controls
      were positive for immunoglobulin (Ig) production. In contrast, 27% of the wells
      containing cells from Graves' patients, and only 3% from controls, were positive
      for TSHrAb. Higher titers of TSHrAbs were produced in cultures containing
      lymphocytes from patients with GD and were predominantly of IgG isotype. All
      patients with GD who had high thyrotropin binding inhibitory immunoglobulins also
      had higher frequencies of TSHr-specific B cells. These findings show that TSHrAb
      producing B cells are present at a higher frequency in the peripheral circulation
      of patients with GD.

PMID- 8137561
TI  - A phenotypic study of CD8+ lymphocyte subsets in infants using three-color flow
      cytometry.
AB  - Flow cytometry is a powerful tool for the multiparametric evaluation of cell
      surface phenotype in patients with HIV disease. Many cell surface molecules can
      be evaluated by three-color flow cytometry and the markers correlated with
      functional activity. It has recently been recognized in adults that the CD8 cell
      is an important lymphocyte subset in HIV disease that correlates with disease
      outcome, but there is little information about CD8 subsets in infants. Therefore,
      we studied infants born to HIV-infected mothers and those born to uninfected
      mothers. No significant differences were seen in phenotypic markers of activation
      (CD38, HLA-DR), maturation (CD45RO, CD45RA), and function (CD28) between
      uninfected infants born to HIV infected or uninfected mothers. In HIV-infected
      infants, a substantial increase in CD8+ CD38+ HLA-DR+ expression was seen. In
      addition, we found that there was a significant increase in the CD8+ CD45RO+
      CD45RA- subset which is characteristic of the memory phenotype. Finally,
      evaluation of CD28 (costimulatory molecule involved in T cell activation), which
      is expressed on almost all CD8 cells at birth, showed that this population was
      significantly reduced in infected infants. These studies suggest that three-color
      flow cytometry is a powerful tool for evaluating phenotypic changes in lymphocyte
      subsets and enhancing our understanding of the pathobiology of HIV disease.

PMID- 8137562
TI  - Abnormal cytokine serum levels correlate with impaired cellular immune responses
      after surgery.
AB  - Serum levels of the interleukins (IL)-2, -1 beta, and -6, tumor-necrosis factor
      alpha (TNF-alpha), and prostaglandin E2 (PGE2) were measured serially before and
      after operation in patients undergoing various surgical procedures. Peripheral
      blood mononuclear cells (PBMC) from the same patients were analyzed before and
      after surgery for proliferative responses in the autologous mixed lymphocyte
      reaction (AMLR) and for cytolytic activity against the natural killer (NK)
      sensitive K562 cell line. In patients who had major surgery, a decrease in IL-2
      levels and increases in IL-1 beta, TNF-alpha, IL-6, and PGE2 levels were observed
      up to 9 days after the operation compared to those of the preoperative values.
      Decreased AMLR responses and NK activity were also observed in PBMC collected 5
      days after surgery. All these changes were more intense in patients who had
      undergone major surgical procedures of increasing severity (i.e., cancer
      patients). Similar, although weaker, changes in cytokine serum levels, AMLR
      responses, and NK activity were also observed in patients undergoing minor
      surgery. Our data suggest that changes in cytokine serum levels may cause
      cellular immune dysfunctions, particularly in patients undergoing major surgery,
      and provide the basis for immune intervention in order to avoid infections
      occurring after major surgery.

PMID- 8137563
TI  - Immunologic detection of the cellular receptor for urokinase plasminogen
      activator.
AB  - The cellular receptor for urokinase plasminogen activator (uPA-R) is a monomeric
      phosphatidylinositol-linked glycoprotein (gp40-65) that may contribute to the
      invasive capacity of tumor and inflammatory cells by focusing the activity of
      urokinase (uPA) in converting plasminogen to plasmin, a serine protease capable
      of degrading extracellular matrix proteins. The further characterization of uPA-R
      has been facilitated by our recent development of a monoclonal antibody, anti
      Mo3f, specific for uPA-R. This mAb bound to uPA-R expressed by phorbol myristate
      acetate-stimulated U-937 cells and by NIH-3T3 cells permanently transfected with
      uPA-R cDNA. In competitive binding assays, anti-Mo3f inhibited the binding of
      fluorescein-conjugated uPA ligand to uPA-R expressed by U-937 cells and uPA-R
      transfectants; conversely, preexposure of cells to saturating quantities of
      exogenous uPA partially blocked the subsequent binding of anti-Mo3f mAb to uPA-R.
      Anti-Mo3f mAb was employed as the capture reagent in an ELISA for the
      quantitation of soluble forms of uPA-R (derived from U-937 cells and recombinant
      uPA-R) which had a sensitivity of approximately 4-12 ng/ml. Anti-Mo3f mAb was
      also applied as a serologic probe for the detection of uPA-R expressed by human
      tumor tissues. By immunoperoxidase staining, anti-Mo3f demonstrated positive
      tumor cell staining in 4 of 16 breast and 7 of 31 prostate carcinomas in formalin
      fixed, paraffin-embedded specimens. These data indicate that the anti-Mo3f mAb
      detects an epitope proximate to or within the ligand binding domain (domain 1) of
      uPA-R and may be useful as a tool for the serologic detection of uPA-R in soluble
      form or associated with human tumors.

PMID- 8137565
TI  - Sneddon's syndrome, anti-cardiolipin antibody and glomerular thrombosis.
AB  - Sneddon's syndrome, cerebrovascular thrombosis and livedo reticularis, is often a
      variant of the "primary" anti-phospholipid syndrome (PAPS). We report a woman
      with PAPS, presenting as Sneddon's syndrome, with renal impairment and glomerular
      thrombosis on renal biopsy. An IgG anti-cardiolipin antibody (aCL) was
      identified. The aCL was purified by affinity chromatography, gel filtration
      chromatography and ion-exchange chromatography, assayed in a modified ELISA and
      found to be of the type that requires the plasma protein beta 2-GPI to bind aCL.
      As beta 2-GPI has anticoagulant properties it is postulated that its interaction
      with aCL has a pathogenic role in the thrombotic lesions associated with aCL.

PMID- 8137564
TI  - Critical re-evaluation of 41 cases of "idiopathic" crescentic glomerulonephritis.
AB  - Despite the availability of different classifications for rapidly progressive
      glomerulonephritis (RPGN), patients with "idiopathic crescentic GN" have not been
      yet inserted as a precisely defined subgroup, pointing to their probable
      heterogenicity. Trying to better define their characteristic, we retrospectively
      analyzed the clinical, histological and immunopathological features of 41
      patients diagnostically labelled "idiopathic RPGN" because they had no evidence
      of systemic disease (including systemic vasculitis), no anti-GBM mediated
      glomerulonephritis and no clearly defined primary glomerulopathy. Starting by a
      thorough morphological review, 2 subgroups were defined: group I (25 patients)
      with variable degrees of intraglomerular necrosis, and group II (16 patients)
      with no intracapillary necrotizing lesions. Group I showed no or minimal
      endocapillary proliferation, intense interstitial infiltrates with periglomerular
      localization, frequent ruptures of Bowman's capsule and mild degree of glomerular
      and/or interstitial sclerosis. 16 patients in this group (64%) had irregular
      deposits of complement C3 at immunofluorescence while the remaining 9 (36%) had
      no immune deposits. Clinically they had no previous history of preceding urinary
      abnormalities, had a mean of 1.8 g/day proteinuria and a positivity for ANCA in
      92% (12/13). In group II there was frequently marked mesangial proliferation,
      scarce interstitial infiltrates, no ruptures of Bowman's capsule and marked
      degrees of glomerulosclerosis and interstitial fibrosis. All patients in this
      group had clearly defined immune deposits of C3 and/or IgG. Clinically 50% of
      these patients had a history of recurrent microhematuria and/or proteinuria, a
      mean of 4.5 g/day proteinuria and negativity for ANCA in all 8 patients
      tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137566
TI  - Cyclosporin A nephropathy: standardization of the evaluation of kidney biopsies.
AB  - An advisory board of nephropathologists with personal experience in the
      evaluation of biopsies from patients treated with cyclosporin A (CyA) was set up
      to address the following problems: 1. Definition of CyA nephropathy as seen in
      patients with autoimmune diseases; 2. Evaluation of the reliability and
      reproducibility of the diagnostic criteria for the different morphological
      lesions seen in CyA nephropathy; 3. Classification of the morphological lesions
      according to their clinical relevance; 4. Estimation of the possible progression
      of CyA nephropathy with continuous CyA therapy. The most frequent lesions
      attributable to CyA therapy in patients with autoimmune diseases are tubular
      atrophy, interstitial fibrosis, and arteriolar hyalinosis. All other lesions are
      rare. The reproducibility and diagnostic reliability is high for tubular atrophy
      and interstitial fibrosis, but low for arteriolar lesions even among experienced
      nephropathologists. The biopsies may be classified according to the severity of
      tubular atrophy, interstitial fibrosis and arteriolar hyalinosis with regard to
      their clinical relevance: In group I (within normal limits), CyA therapy can be
      continued; in group III (moderate-to-severe CyA-related lesions), CyA should be
      stopped if possible. Among group II biopsies (slight CyA-related abnormalities),
      no recommendation can be made in the absence of a second biopsy after a further
      year of CyA therapy. No clear-cut answer can be given concerning the progression
      of CyA-induced lesions. However, no significant progression has been found in the
      cases studied to date.

PMID- 8137567
TI  - Morphological and functional renal effects of long-term low-dose cyclosporin A
      treatment in patients with rheumatoid arthritis.
AB  - To explore the possible nephrotoxic effects of low-dose cyclosporin A (CyA)
      treatment, we analyzed the data from 10 patients, aged 35-66 years (mean 51.8
      years), who had a clinical diagnosis of rheumatoid arthritis and no known kidney
      disease. The study protocol included consecutive kidney biopsies and a
      pretreatment biopsy in all cases. A second biopsy was taken after 5-20 months
      (mean 17.8 months) of treatment and, in seven patients, a third biopsy was
      performed after 30-46 months (mean 38.6 months). Evaluation of the kidney
      biopsies included a semiquantitative estimation of different histological
      parameters as well as assessment of a chronicity index (CI). Transmission
      electronmicroscopic examination was performed on all biopsies. There was a
      significant reduction of glomerular function at the time of both the second (n =
      10; p < 0.01) and third (n = 7; p < 0.05) biopsies. Five patients showed an
      increase in CI on the second biopsy and five on the third biopsy in comparison to
      pretreatment values. Only one patient showed a progressive increase in CI on
      three consecutive biopsies. The mean CI increased on both the second (n = 10) and
      third (n = 7) biopsies compared with baseline, but there was no increase on the
      third biopsy from the second. The morphological findings were, as a rule, slight
      or moderate, and focal interstitial fibrosis, tubular atrophy and arteriolar
      hyalinosis were the most consistent findings. Although even low-dose CyA
      treatment may be nephrotoxic and may induce morphological alterations in the
      kidney, such changes do not occur in all patients and may not necessarily be
      progressive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137568
TI  - The kidney in cyclosporin A-treated diabetic patients: a long-term
      clinicopathological study.
AB  - This was an analysis of the renal investigations performed in 248 cyclosporin A
      (CyA)-treated patients who had recent-onset type I insulin-dependent diabetes
      mellitus (IDDM) to assess the clinicopathological relationships, risk factors and
      predictive indices of CyA nephrotoxicity, and renal function observed with
      different CyA treatment regimens. There were four different protocols, using
      initial CyA dosages ranging from 7.5 to 10 mg/kg/day, with dose modification
      according to serum creatinine concentration, which was measured regularly in some
      patients for up to 9 years after starting treatment. Kidney biopsies were
      obtained from 125 patients (74 adults and 51 children) who had received only CyA
      for an average duration of 13 months before biopsy and had no other sources of
      renal injury at this stage of IDDM. Of these patients, 58% showed normal or
      minimal changes on biopsy, 26% showed slight abnormalities, and 16% showed medium
      grade (grade III nephropathy) abnormalities. Lesion severity was related to the
      degree of interstitial fibrosis and tubular atrophy which, in turn, was related
      to the use of high maximum CyA dosages. Patients' age, and excessive CyA dose and
      blood trough levels were the main risk factors, and serum creatinine increase was
      the best predictive factor of CyA-induced nephropathy. However, CyA-induced renal
      dysfunction was essentially reversible on dosage reduction, and morphological
      changes were not followed by progressive renal insufficiency when CyA doses were
      low and adjusted according to serum creatinine levels. We conclude that, at
      present, it is recommended that low-dose CyA in combination with other non
      nephrotoxic immunosuppressive strategies be used in patients with IDDM.

PMID- 8137569
TI  - Pregnancy-related complications in women with reflux nephropathy.
AB  - Three hundred and forty-five pregnancies in 137 women with reflux nephropathy
      have been studied. All pregnancies took place after 1971. Overall foetal loss was
      48 (14%) of which only 6 (2%) were therapeutic abortions. Maternal complications
      (urine infection, hypertension, proteinuria, oedema, deterioration in renal
      function, hematuria or renal stones) occurred alone or in combination in 39% of
      pregnancies. Fifty-two pregnancies took place in women with plasma creatinine
      (P.Cr > 0.11 mmol/l) prior to conception. Foetal loss after 12 weeks gestation
      (excluding therapeutic abortions) was 18% compared with 8% in the 104 pregnancies
      where maternal P.Cr was known to be < or = o.11 per/l at conception (p < 0.05).
      Maternal complications were also more common in the impaired renal function group
      (p < 0.001). Comparison of pregnancies in women with unilateral versus bilateral
      renal scarring revealed no significant difference in foetal loss but an increased
      incidence of over 50% maternal complications in the bilateral renal scar group (p
      < 0.01). The incidence of pre-eclampsia was higher in women with bilateral renal
      scars, 50 (24%) than in women with unilateral scars 8 (7%) (p < 0.001).
      Persistent vesicoureteric reflux was not associated with increased foetal loss or
      maternal risk. Impaired renal function prior to conception is associated with
      increased foetal and maternal complications in pregnancy. Bilateral renal
      scarring is associated with increased maternal complications during pregnancy.

PMID- 8137570
TI  - Microhematuria associated with microproteinuria: an intriguing new clinical
      entity.

PMID- 8137571
TI  - Abnormal protein excretion.

PMID- 8137572
TI  - Total or subtotal parathyroidectomy in uremic patients?

PMID- 8137573
TI  - Which hyperparathyroid state is better for bone densitometry in uremic patients?

PMID- 8137574
TI  - SPECT evaluation of unilateral spondylolysis.
AB  - Three patients with unilateral spondylolysis were evaluated with SPECT and Lumbar
      CT. All three cases had positive scans. However, the SPECT images were unique to
      each case. Therefore, the interpretation of the SPECT activity was undertaken in
      terms of the known natural history of both unilateral and bilateral
      spondylolysis.

PMID- 8137575
TI  - Increased F-18 FDG accumulation in an acute fracture.
AB  - Markedly increased FDG uptake was noted in a 2-week-old fracture of the clavicle
      and scapula in a 24-year-old man. This finding emphasizes the need to consider
      benign etiologies such as trauma for focally increased FDG accumulation in bone.

PMID- 8137576
TI  - The use of CT and scintigraphy in diagnosing a cystic ameloblastoma of the jaw.
AB  - The results of CT and bone scintigraphy of eight patients with a histologically
      proven cystic ameloblastoma of the jaw are reviewed. CT imaging revealed
      unilocular and multilocular cystic lesions with well-defined thin cystic borders
      in all patients. CT also detected increased density in the bone marrow adjacent
      to the cystic radiolucent lesion, suggesting that the ameloblastoma had spread
      into the cancellous bone. Further, nuclear bone scans showed a doughnut-shaped
      pattern in all cases and radioactivity beyond the cystic wall, indicating
      intramedullary extension of the ameloblastoma. The use of these two modalities
      was found to be complementary in delineating the full nature and extent of the
      pathologic lesion.

PMID- 8137577
TI  - Diffuse increased renal uptake on bone scintigraphy in acute tubular necrosis.
AB  - Acute renal failure after exercise with frank pain and patchy renal
      vasoconstriction is a clinical syndrome that occurs in young, previously healthy
      persons. The authors describe a 24-year-old man who had this syndrome. CT scan
      showed wedge-shaped contrast enhancement of both kidneys, which suggested patchy
      renal vasoconstriction. Tc-99m MDP imaging revealed diffuse increased uptake of
      both kidneys. After renal function was improved, Tc-99m MDP imaging showed normal
      uptake of both kidneys. Acute renal failure due to acute tubular necrosis was
      confirmed by renal biopsy. The authors conclude that Tc-99m MDP may be useful in
      evaluation of acute renal failure after exercise with flank pain and patchy renal
      vasoconstriction due to acute tubular necrosis.

PMID- 8137578
TI  - Renal artery stenosis diagnosed with Tc-99m DMSA scintigraphy.
AB  - Captopril-enhanced renal scintigraphy with Tc-99m DMSA was performed in an 11
      year-old boy with hypertension. This showed a significant reduction in function
      of the right kidney. Renal arteriography was performed and showed two renal
      arteries on the right, the major one with stenosis. This case illustrates the
      possible role that scintigraphy with Tc-99m DMSA can play in the diagnosis of
      renovascular hypertension.

PMID- 8137579
TI  - Renal artery pseudoaneurysm demonstrated on radionuclide scintiscan.
AB  - The authors present a case of renal artery pseudoaneurysm demonstrated on the Tc
      99m DTPA dynamic study. On the blood flow image, localized increased activity was
      noted in the are of the renal hilus. This activity disappeared on the subsequent
      sequential renal images.

PMID- 8137580
TI  - Technetium-99m methoxy isobutyl isonitrile simultaneous evaluation of ventricular
      function and myocardial perfusion in patients with congenital heart disease.
AB  - The authors evaluated the clinical applications of Tc-99m methoxy isobutyl
      isonitrile (MIBI) in the simultaneous assessment of ventricular function and
      myocardial perfusion in patients with congenital heart disease. Global
      ventricular function was assessed by first-pass ECG gated study. Myocardial
      perfusion was evaluated on images performed 1 hour after the injection of the
      tracer. Regional wall motion and systolic thickening were assessed by gated study
      acquired after the perfusion study. Two young patients were studied after a
      surgical Glenn procedure. The first patient, with a history of transposition of
      the great vessels and univentricular heart, had an ejection fraction of 44%. The
      left ventricle was dilated and the right ventricle was not appreciable. The
      septal and inferoapical regions showed reduced perfusion and reduced systolic
      thickening. The second patient, with a history of pulmonary atresia, septal
      defect and left ventricular hypoplasia, had a right ventricular ejection fraction
      of 37%. Regional wall motion, systolic thickening, and myocardial perfusion were
      normal. The right ventricle was hypertrophic and larger than the left ventricle.
      Thus, a single injection of Tc-99m MIBI allows noninvasive simultaneous
      assessment of global and regional ventricular function and myocardial perfusion
      in young patients with complicated congenital heart disease.

PMID- 8137581
TI  - Choledochal cyst.
AB  - A case of a choledochal cyst occurring in a 21-year-old woman is presented. The
      spectrum of congenital dilatation of the biliary tree and the contributions of
      various imaging modalities and procedures in the condition are discussed,
      including the use of nuclear medicine biliary imaging.

PMID- 8137582
TI  - Tc-99m DISIDA hepatobiliary scintigraphy in AIDS cholangitis.
AB  - Sixteen patients with documented AIDS cholangitis who underwent Tc-99m DISIDA
      hepatobiliary scintigraphy were retrospectively reviewed to assess the spectrum
      of changes observed in this disease. AIDS cholangitis was documented by either
      ERCP with aspiration/biopsy or the presence of typical sonographic/CT
      abnormalities with positive stool culture and a minimum of 6 months follow-up.
      Images were graded as regards parenchymal function (blood pool clearance, peak
      parenchymal activity, and degree of parenchymal retention), gallbladder
      visualization, presence of ductal dilatation, and time of intestinal activity.
      Three patterns were identified: 1) focal ductal dilatation with focal narrowing
      and focal or diffuse parenchymal retention; 2) ductal dilatation, without
      narrowing, and diffuse parenchymal retention; and 3) severe diffuse parenchymal
      retention with or without ductal abnormality. All 16 studies revealed abnormal
      parenchymal retention. Gallbladder nonvisualization was demonstrated in nine
      studies and delayed in two. The hepatobiliary scan is a very sensitive technique
      for evaluating AIDS cholangitis. Although a spectrum of findings may be observed,
      parenchymal retention with some degree of ductal abnormality is the most commonly
      observed pattern.

PMID- 8137583
TI  - Intraperitoneal distribution imaging prior to chromic phosphate (P-32) therapy in
      ovarian cancer patients.
AB  - This study addressed the technique of intraperitoneal distribution imaging (IDI).
      A literature search (MEDLINE database) revealed wide variations in IDI techniques
      without a basis for comparison. From April 1990 to September 1992, the authors
      studied 8 patients (age 43-65 years) with ovarian cancer. A total of 1000 ml of
      normal saline and 1 mCi of Tc-99m SC was infused intraperitoneally for IDI. In
      one patient loculation was observed, but only 250 ml of normal saline was infused
      with Tc-99m SC. A repeat study using our standard technique rendered free
      intraperitoneal distribution in this patient, as well as in the other seven
      cases. Some investigators recommend low volumes, but in our experience this
      produced the finding of pseudoloculation, which could change treatment
      inappropriately. Although the number of patients studied at our institution was
      small, administration of 1 liter intraperitoneally provided consistent IDI
      results.

PMID- 8137584
TI  - Thyroid hormones in differentiated thyroid cancer.
AB  - In a study of 136 differentiated thyroid cancer patients referred for radioiodine
      therapy since January 1991, it was observed that 80 patients had metastatic
      disease. Of them, 51 had elevated levels of thyroglobulin (Tg), and of these 51
      there were 15 patients who had functioning metastases with evidence of thyroid
      hormone synthesis by these metastases. All but 1 of these 15 cases with normal
      hormone levels in the circulation were follicular carcinomas with skeletal
      metastases. The response of these patients to radioiodine was poor. The group of
      patients with high Tg levels but low hormone synthesis and low circulating
      hormones responded better to radioiodine. Patients with low Tg levels and low
      hormone synthesis showed good response to radioiodine--especially patients with
      residual thyroid tissue after surgery and those with nodal disease.

PMID- 8137585
TI  - Dialysis shunt infection. Scintigraphy and MRI correlation.

PMID- 8137586
TI  - Tc-99m MIBI brain SPECT in the diagnosis of recurrent glioma.

PMID- 8137587
TI  - Left hepatic and common hepatic ductal bile leaks demonstrated by Tc-99m HIDA
      scan and percutaneous transhepatic cholangiogram.

PMID- 8137588
TI  - Tc-99m MDP uptake in osteopoikilosis.
AB  - A Tc-99m bone scan of a patient with classic roentgenographic findings of
      osteopoikilosis revealed multiple foci of increased activity that corresponded to
      many of the sclerotic foci on the roentgenograms. The authors presume that the
      abnormal bone scan in this patient reflects active osseous remodeling, similar to
      what has been observed in bone islands. Previous reports have emphasized the
      critical role of the radionuclide bone scan for distinguishing osteopoikilosis
      from osteoblastic bone metastases in patients with a known or suspected primary
      malignancy. In a young patient, an abnormal bone scan does not exclude the
      diagnosis of osteopoikilosis if the roentgenographic findings are characteristic
      of that entity.

PMID- 8137589
TI  - Ventilation-perfusion mismatch caused by extrinsic compression of the pulmonary
      artery. Correlative imaging.

PMID- 8137590
TI  - Differentiation between residual cancer and thymic hyperplasia in malignant non
      Hodgkin's lymphoma with somatostatin receptor scintigraphy.

PMID- 8137591
TI  - Technetium-99m exametazime brain SPECT and magnetic resonance images in the
      diagnosis of herpes simplex encephalitis.

PMID- 8137592
TI  - The "pseudo-pseudoaneurysm". Left ventricular pseudoaneurysm mimicked by ectopic
      spleen.

PMID- 8137593
TI  - Right ventricular filling defect resulting from severe pectus excavatum.

PMID- 8137594
TI  - Radionuclide diagnosis of dual abdominal pathology.

PMID- 8137595
TI  - Standards for bioequivalence of inhaled products.

PMID- 8137596
TI  - Clinical pharmacokinetics of tenoxicam.
AB  - Tenoxicam is a nonsteroidal anti-inflammatory drug (NSAID) in the oxicam group.
      It is completely absorbed by the oral route and is about 99% protein bound in
      human plasma. Intake of food delays absorption without affecting bioavailability.
      There is no evidence for enterohepatic recycling of the drug in humans. Peak
      plasma concentrations of 2.7 mg/L (range 2.3 to 3.0 mg/L) have been reported in
      different groups of fasted healthy volunteers 1.9 hours (1.0 to 5.0 hours) after
      a single oral dose of 20mg. A mean elimination half-life of 67 hours (49 to 81
      hours) has been estimated. Tenoxicam demonstrates linear single-dose
      pharmacokinetics over doses of 10 to 100mg. Because of its low lipophilicity and
      high degree of ionisation in blood (approximately 99%), the drug is poorly
      distributed to body tissues and is slowly taken up by hepatic cells. A small
      apparent volume of distribution of 9.6L (7.5 to 11.5L), and low total plasma
      clearance of 0.106 L/h (0.079 to 0.142 L/h), have been reported in different
      groups of healthy volunteers after oral and intravenous administration. Peak
      concentrations of tenoxicam in synovial fluid are less than one-third of those in
      plasma and they appear later, 20 hours (10 to 34 hours) after an oral dose. A
      parallel decrease in synovial fluid and plasma concentrations with time for both
      total and unbound tenoxicam has been reported. In vivo pH differences between
      synovial fluid and plasma in patients with rheumatoid arthritis may indicate
      significantly lower concentrations of unbound ionised tenoxicam in synovial fluid
      than in plasma. Data on relative binding capacities for tenoxicam in plasma and
      synovial fluid, and between different groups of individuals, are not conclusive.
      The protein binding of tenoxicam is pH dependent. The drug is almost entirely
      eliminated by liver metabolism. The 2 main metabolites, the inactive 5'-hydroxy
      and 6-O-glucuronidated forms, are excreted in urine and bile, respectively. The
      existence of additional metabolites in human bile has been suggested. Urinary
      excretion of the 5'-hydroxy metabolite decreases with reduced renal function. The
      5'-hydroxy metabolite is detected in plasma in concentrations 1 to 5% of the
      parent compound and its decline parallels that of the parent compound (formation
      rate limitation). Urinary and faecal excretion of unchanged tenoxicam is less
      than 1% of the administered dose. No significant amounts of unchanged tenoxicam
      are excreted in bile. Tenoxicam shows nearly linear pharmacokinetics during
      multiple-dose administration.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8137597
TI  - Drug binding in plasma. A summary of recent trends in the study of drug and
      hormone binding.
AB  - The ligands are generally bound in plasma to a significant extent by several
      transport proteins (both high and low affinity), irrespective of their endogenous
      or exogenous origin. The protein binding of endogenous compounds (such as
      hormones) exhibits higher affinity and specificity than those of exogenous
      compounds (such as drugs). For plasma proteins that bind the same ligand(s),
      structural similarities or a common genetic origin may be found, although this is
      not a general rule. Alterations in ligand binding may be due to modifications of
      either the structure or the level of the binding protein. These modifications may
      result from genetic make up, physiology or pathology. In some situations, plasma
      binding may impair the distribution of drugs to tissues, with drug distribution
      then mainly restricted to the distribution compartment of the drug-binding
      protein. In other instances, the plasma drug-binding is permissive, and does not
      limit drug distribution to tissues. A given drug-transport protein system may
      have either a permissive or a restrictive effect on the drug distribution,
      depending on the tissue. The physiological significance of the high-affinity
      transport proteins is not completely understood. These proteins may increase the
      plasma concentration of poorly hydrosoluble ligands, ensure a more uniform tissue
      distribution and increase the life of the ligands. The life of the protein may
      also be increased by ligand binding. High-affinity transport proteins are also
      involved in some specific carrier mediated transfer mechanisms. It is possible to
      demonstrate structure-binding relationships or binding selectivity for the plasma
      transport proteins, but these are quite independent of relationships observed at
      the receptor level.

PMID- 8137598
TI  - Pharmacogenetic phenotyping and genotyping. Present status and future potential.
AB  - Enzymes that metabolise foreign compounds exhibit a large degree of
      interindividual variability in their levels of expression. In a number of
      instances this variability can be accounted for by null or variant alleles
      resulting from mutations in genes encoding these enzymes. Human variability in
      drug metabolism can be determined by biochemical and pharmacological assays. In
      cases where a genetic change has been characterised, polymerase chain reaction
      techniques have been developed to diagnose metabolism deficiencies. Genetic
      differences in certain foreign compound metabolising enzymes such as glutathione
      S-transferase M1, N-acetyltransferase 2 and CYP2D6 have been shown to be
      associated with risk for developing environmentally and occupationally based
      diseases such as cancer. Drug therapy can also be compromised by the existence of
      genetic deficiencies in a number of enzymes, including CYP2D6. It is anticipated
      that determination of an individual's drug metabolism capabilities by use of
      phenotyping and genotyping tests will allow for more rational and safe drug
      administration protocols.

PMID- 8137599
TI  - Clinical pharmacokinetics of ramipril.
AB  - Ramipril is a long-acting nonsulfhydryl angiotensin converting enzyme (ACE)
      inhibitor introduced for clinical use about a decade ago. Ramipril is a prodrug
      that undergoes de-esterification in the liver to form ramiprilat, its active
      metabolite. Ramipril rapidly distributes to all tissues, with the liver, kidneys
      and lungs showing markedly higher concentrations of the drug than the blood.
      After absorption from the gastrointestinal tract, rapid hydrolysis of ramipril
      occurs in the liver. In the therapeutic concentration range, protein binding of
      ramipril and ramiprilat is 73 and 56%, respectively. Ramiprilat binds to ACE with
      high affinity at concentrations similar to that of the enzyme and establishes
      equilibrium slowly. Although ramipril is metabolised by hepatic and renal
      mechanisms to both a glucuronate conjugate and a diketopiperazine derivative,
      most of the drug is excreted in the urine as ramiprilat and the glucuronate
      conjugate of ramiprilat. Elimination from the body is characterised by a
      relatively rapid initial phase with a half-life of 7 hours and a late phase with
      a half-life of about 120 hours. No clinically significant pharmacokinetic
      interactions between ramipril and other drugs have been reported. The drug has
      been generally well tolerated with the most prevalent adverse effects being
      dizziness (3.4%), headache (3.2%), weakness (1.9%) and nausea (1.7%). Ramipril is
      an effective and well tolerated drug for the treatment of hypertension and
      congestive heart failure in all patients, including those with renal or hepatic
      dysfunction, and the elderly.

PMID- 8137602
TI  - Tacrine granted marketing approval for Alzheimer's disease.

PMID- 8137601
TI  - Statistics or pharmacokinetics?

PMID- 8137600
TI  - Cost considerations in therapeutic drug monitoring of aminoglycosides.
AB  - Aminoglycoside antibiotics are very important in the treatment of Gram-negative
      infections and as synergistic agents for the treatment of staphylococcal and
      streptococcal (group B streptococci and enterococci) infections. However, these
      agents have a narrow therapeutic index. Thus, a number of new antibiotics have
      been introduced in an attempt to reduce the number of patients treated with
      aminoglycosides. Unfortunately, these new antibiotics tend to be costly, and are
      often associated with development of resistance and treatment failure. Data
      suggest that a pharmacokinetic/pharmacodynamic relationship exists for some
      aspects of efficacy and toxicity of aminoglycosides. Serum drug concentrations
      and/or tissue accumulation are related to the development of nephrotoxicity, and
      individualised pharmacokinetic monitoring may decrease rates of nephrotoxicity.
      Peak serum drug concentrations and the ratio of peak serum drug concentration to
      minimum inhibitory concentration appear to correlate with clinical efficacy in
      the treatment of patients with bacteraemia or pneumonia. Therapeutic drug
      monitoring (TDM) has been used to optimise aminoglycoside therapy and reduce
      toxicity. Cost-effective approaches to drug selection and TDM are important
      considerations in the proper use of aminoglycosides.

PMID- 8137603
TI  - Cisapride marketed for use in gastroesophageal reflux disease.

PMID- 8137604
TI  - Recognition of severe cefixime-induced diarrhea.

PMID- 8137605
TI  - Sotalol: a new class III antiarrhythmic agent.
AB  - The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse
      effects, and dosage of sotalol hydrochloride are reviewed. The chemical name of
      sotalol hydrochloride is 4'-[1-hydroxy-2
      (isopropylamino)ethyl]methanesulfonanilide monohydrochloride. Sotalol is a class
      III antiarrhythmic that prolongs the action potential and refractoriness of
      cardiac tissue and has potent nonselective beta-blocking activity. Sotalol is
      well absorbed after oral administration. The pharmacokinetics of sotalol can be
      described by an open, linear, two-compartment model. The drug is eliminated
      primarily by the kidneys; mean elimination half-life is 12 hours. Sotalol has
      been found to be effective in controlling life-threatening ventricular
      arrhythmias, including sustained ventricular tachycardia, ventricular
      fibrillation, and premature ventricular complexes. Although sotalol has FDA
      approved labeling for use in the treatment of ventricular arrhythmias only, it is
      also effective against a variety of supraventricular arrhythmias. Noncardiac
      adverse effects include fatigue, impotence, depression, headache, nausea,
      diarrhea, and increased triglyceride levels. Cardiovascular adverse effects
      include atrioventricular block, bradycardia, hypotension, exacerbation of heart
      failure, and polymorphic ventricular tachycardia. Overall, 11-21% of patients
      experience adverse effects; 6-18% of these patients have reactions serious enough
      to warrant the discontinuation of sotalol therapy. The initial dosage of oral
      sotalol hydrochloride in adults is 80 mg twice daily or 160 mg once daily; the
      dosage can be increased every three to four days in increments of 40-160 mg/day
      to a maximum of 480 mg/day. Sotalol is useful in the control of intractable, life
      threatening ventricular arrhythmias, as well as a variety of supraventricular
      arrhythmias, in patients who do not respond to or are intolerant of more
      conventional antiarrhythmics.

PMID- 8137606
TI  - Low-molecular-weight heparins for the treatment of deep-vein thrombosis.
AB  - The pharmacologic characteristics of low-molecular-weight (LMW) heparins and
      unfractionated heparin are reviewed, and clinical trials comparing LMW heparins
      with unfractionated heparin for the initial treatment of deep-vein thrombosis
      (DVT) are described. LMW heparins are derived from native heparin and range in
      mass from 3000 to 8000 daltons. All LMW heparins contain the antithrombin III
      specific pentasaccharide unit found on unfractionated heparin. LMW heparins are
      stronger inhibitors of factor Xa than unfractionated heparin, but their
      mechanisms of action, like that of unfractionated heparin, is predominantly the
      inhibition of thrombin. The efficacy of LMW heparins in the prophylaxis of DVT is
      not correlated with activated partial thromboplastin time (APTT); monitoring of
      APTT or anti-factor Xa may not be necessary. Compared with unfractionated
      heparin, LMW heparins have a lower affinity for heparin cofactor II, platelet
      factor 4, von Willebrand factor, and vascular epithelium. Subcutaneously
      administered LMW heparins are more bioavailable than s.c. unfractionated heparin.
      In clinical trials in patients with DVT, LMW heparins (dalteparin, enoxaparin,
      nadroparin, and tinzaparin) have resulted in venography scores similar to those
      obtained with unfractionated heparin. Frequencies of recurrent thromboembolism
      and bleeding complications were also similar. Dalteparin and logiparin were
      effective when administered in single daily subcutaneous doses; this could lead
      to lower treatment costs. Additional studies are needed to compare LMW heparins
      and unfractionated heparin with respect to efficacy, bleeding complications,
      mortality, and cost. LMW heparins may be valuable alternatives to unfractionated
      heparin for the treatment of DVT.

PMID- 8137607
TI  - Efficacy of nutritional supplements used by athletes.
AB  - Findings on the efficacy of nutritional supplements used by athletes are
      reviewed. Many athletes have turned away from anabolic steroids and toward
      nutritional supplements in the hope of gaining a competitive edge without
      threatening their health. Athletes may require slightly more protein than
      sedentary people do to maintain positive nitrogen balance, but it is dubious
      whether extra dietary protein will help someone to achieve athletic goals.
      Purified amino acids have become a popular if expensive form of protein
      supplementation; there is no scientific evidence, however, to support their use.
      Excessive protein supplementation can lead to dehydration, gout, liver and kidney
      damage, calcium loss, and gastrointestinal effects. Supplementation with vitamins
      and minerals in excess of recommended daily allowances appears to have no effect
      on muscle mass or athletic performance. Other substances touted as having
      ergogenic properties are carnitine, cobamamide, growth hormone releasers,
      octacosanol, and ginseng; again, there is no reliable scientific evidence to
      support claims that products containing these compounds have ergogenic potential,
      and heavy supplementation may lead to adverse effects. Nutritional supplements
      are promoted through unsubstantiated claims by magazine advertisements, health
      food stores, coaches, and other sources. The FDA considers nutritional
      supplements to be foodstuffs, not drugs, and therefore has not required that they
      be proved safe and effective. Dosage guidelines are inadequate, and quality
      control is poor. The FDA has begun to revise regulations governing labeling and
      health claims for these products. There is little if any evidence that
      nutritional supplements have ergogenic effects in athletes consuming a balanced
      diet, and some products have the potential for harm.

PMID- 8137608
TI  - Predicting vancomycin pharmacokinetics by using aminoglycoside pharmacokinetics.

PMID- 8137609
TI  - Modified Michaelis-Menten equation for estimating unbound-phenytoin
      concentrations.

PMID- 8137610
TI  - Accuracy of unbound-quinidine concentration determination after ultrafiltration.

PMID- 8137611
TI  - Criteria for use of epoetin alfa in adult cancer and orthopedic-surgery patients.

PMID- 8137612
TI  - Update on malabsorption.

PMID- 8137613
TI  - Diagnosis and treatment of chronic viral hepatitis.

PMID- 8137614
TI  - Metastatic melanoma of the gastrointestinal tract: a review of the literature.
AB  - Malignant melanoma metastases to the GIT are not uncommon, and often the
      diagnosis is delayed. Within the GIT, the small bowel is most frequently
      involved, followed by the stomach, large bowel, and esophagus. Patients with
      acute complications such as bleeding, perforation, intussusception, and
      obstruction require urgent surgical intervention. The diagnosis of metastatic
      melanoma is pathologically confirmed at surgical exploration in 80% of patients,
      by endoscopic procedures in 15%, and percutaneous biopsy in 5%. Small or large
      bowel resection for hemorrhage or obstruction provides symptomatic relief in 79
      92% of patients with a postoperative mortality rate of 5%. Reported 1- and 5-year
      survival rates are 44% and 9-19%, respectively. Because of the acceptable
      morbidity in select symptomatic patients, surgical palliation should be
      undertaken when the quality of life may be improved. Malignant metastatic
      melanoma involving the GIT has a dismal prognosis. The symptoms are commonly
      nonspecific and not recognized antemortem. Gut metastases signify an advanced
      stage of disease. Chemotherapy and immunotherapy have been ineffective in
      prolonging survival for these patients. For patients with general good health and
      symptomatic metastases, their disease can be excised with limited morbidity and
      mortality while providing effective and lasting palliation. Because of this,
      surgical resection is warranted in many patients with symptomatic
      gastrointestinal metastases from melanoma.

PMID- 8137615
TI  - Management of chronic pancreatitis.
AB  - Chronic pancreatitis is an inflammatory disorder that leads to impairment of
      exocrine and endocrine function of the pancreas. Anatomic and functional
      definition of this disorder can result in successful medical, endoscopic, or
      surgical treatment. Enzyme supplementation in appropriate formulation and dosage
      may alleviate the cardinal symptoms of abdominal pain and diarrhea. Prevention of
      this disorder may be possible by early identification of excessive alcohol
      consumption with intervention.

PMID- 8137616
TI  - Cholestasis.

PMID- 8137617
TI  - A second look at obesity.

PMID- 8137618
TI  - Barrett's esophagus: current and future management.
AB  - Barrett's esophagus is considered to be a preneoplastic condition associated with
      chronic reflux esophagitis. The risk of neoplasia is difficult to assess but
      appears to be increased by about 40-fold with an incidence of 1:200 patient
      years. Diagnosis of Barrett's esophagus is made by endoscopy with biopsy of the
      suspected area. Barrett's is histologically confirmed by the presence of
      specialized epithelium (intestinal metaplasia). Histologic findings of low-grade
      dysplasia and high-grade dysplasia have increased neoplastic risks. The
      development of cancer within a Barrett's esophagus appears to be related to a
      sequence of molecular events beginning with the loss of the tumor suppressor gene
      p53 and followed by the loss of the 5q chromosome. Current management of
      Barrett's esophagus includes controlling reflux esophagitis and following
      selected patients with surveillance biopsies. Surgical resection has been
      advocated for patients with high-grade dysplasia, although this has not been
      proven to be a cost-effective strategy. Prospective management options include
      long-term omeprazole use, flow cytometry, endosonography, laser-induced
      fluorescence, photodynamic therapy, and argon laser therapy. However, long-term
      observation is needed to determine whether these approaches can impact upon
      cancer development.

PMID- 8137619
TI  - Diagnosis and treatment of constipation.

PMID- 8137620
TI  - Evaluation of abnormal liver tests.
AB  - The evaluation of elevated serum aminotransferase levels requires attention to
      clinical clues obtained in the history and physical examination. The likelihood
      that an aminotransferase abnormality reflects significant liver disease is
      enhanced if the following occur: (1) more than one liver enzyme is abnormal; (2)
      the abnormalities are associated with clinical signs or symptoms of liver
      disease; (3) the enzyme level is high; or (4) the abnormalities are present for >
      6 months. The subsequent laboratory investigation becomes relatively
      straightforward in confirming a cause for the abnormalities before initiating
      therapy.

PMID- 8137621
TI  - Carcinoma of the esophagus: an overview.

PMID- 8137622
TI  - Alcoholic liver disease.
AB  - Alcoholism alone, or in combination with other etiologic factors, is a common
      cause of liver failure because of hepatitis, cirrhosis, and/or hepatocellular
      cancer. Encountered morphologic and functional alterations are due to immunologic
      reactivity to cell injury evoked by acetaldehyde, other noxious factors, and
      nutrient deficits. Less than 20% of subjects who consume over 90 g/d of ethanol
      for years develop progressive liver damage and cirrhosis. Alcoholism should be
      interrupted in patients with subclinical hepatic abnormalities. Although early
      alcoholic hepatitis and cirrhosis respond to abstinence and symptomatic therapy,
      available measures have little influence on functional and morphologic
      abnormalities in end-stage alcoholic liver disease. Resection is desirable for
      localized hepatocellular cancer, and liver transplantation should be considered
      for cirrhosis. Transplantation is appropriate for patients with uncomplicated end
      stage alcoholic cirrhosis in whom evidence of liver failure can be controlled
      during a 6-month period of rehabilitation. Continuous psychosocial support is
      required to prevent recividism in the posttransplant immunosuppressed alcoholic.

PMID- 8137623
TI  - New progestogens in oral contraception.
AB  - The major developments in combined oral contraceptives (COCs) have been a
      reduction in the total dose of both the oestrogen and progestogen administered
      per cycle and the introduction of new progestogens which are claimed to be more
      'selective' than the older ones. This review examines in detail the clinical
      efficacy of the new COCs, where possible in comparison with those containing
      levonorgestrel or norethisterone, and their pharmacological effect on
      carbohydrate and lipid metabolism, haematological factors, pituitary-ovarian
      function and serum protein and androgen concentrations. Based mainly on the
      pharmacological evidence, the newer COCs are an improvement over the older low
      dose formulations and are clearly preferable to the high-dose ones. However, the
      older low-dose COCs, despite many years of use, have not resulted in a high
      incidence of adverse effects. The increasing use of the new COCs, as evidenced by
      their increasing market share throughout Europe, does indicate that they have
      been well accepted in clinical practice.

PMID- 8137624
TI  - Clinical comparison of two low-dose oral contraceptives, Minulet and Mercilon, in
      women over 30 years of age.
AB  - A comparative study of two low-dose oral contraceptives, gestodene (GES) 75
      mcg/ethinyl oestradiol (EE) 30 mcg and desogestrel (DES) 150 mcg/EE 20 mcg, was
      conducted in women over 30 years of age. This randomised, open-label study was
      organised in Denmark, Italy, New Zealand and United Kingdom. A total of 505 women
      received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles. The
      two groups were comparable in terms of demographic and gynaecologic
      characteristics at baseline. However, the menstrual flow length was slightly
      longer in the GES/EE group before the start of the treatment. The mean age (+/-
      SD) was 35 +/- 4 years in the GES/EE group and 35 +/- 5 years in the DES/EE
      group. The subjects in the GES/EE group contributed data for a total of 2800
      cycles and those in the DES/EE group, data for 2796 cycles. There were no
      pregnancies on medication with either preparation. The results showed that there
      were significantly more normal cycles in the GES/EE group for cycles 1 to 6.
      Irregular bleeding between withdrawal bleeds occurred in 10% of GES/EE and 18.5%
      of DES/EE cycles. Absence of all bleeding was reported in 29 (1%) and 63 (2%)
      cycles, respectively. The incidence of missed pills was low in both groups (11%
      of cycles). No significant differences were observed in cycle length or
      withdrawal bleeding episode length. Withdrawal bleeding mean intensity was
      statistically significantly greater with GES/EE. However, for both preparations,
      the mean intensity was close to light bleeding. No clinically significant
      differences were noted in weight, blood pressure, Papanicolaou smears or
      laboratory data. Sixty-eight (13.5%) subjects in the GES/EE group and 64 (12.8%)
      in the DES/EE group discontinued before the end of the study. Among them, 37 (7%)
      and 40 (8%) in the respective groups withdrew because of adverse reactions. There
      was no difference between groups in terms of primary reasons for withdrawal. The
      most frequently reported complaints that led to discontinuation in both groups
      were headache, nausea and metrorrhagia. Breast tenderness led to the
      discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group. These
      results show excellent cycle control, efficacy and very low rate of side effects
      with both GES/EE and DES/EE. These low-dose oral contraceptives could be well
      suited to healthy nonsmoking women requiring contraception up to the age of
      menopause.

PMID- 8137625
TI  - Contraceptive methods and risk of pelvic endometriosis.
AB  - The relation between contraceptive methods and risk of pelvic endometriosis has
      been analyzed in a case-control study. Cases were 376 women with laparoscopically
      or laparotomically confirmed pelvic endometriosis admitted to a network of
      Obstetrics and Gynecology Clinics in Lombardy, Northern Italy. Controls were 522
      women admitted for acute non-gynecological and non-obstetrics conditions to the
      same hospitals where cases had been identified. A total 153 women (40.3%) out of
      the 377 cases and 154 (29.7%) out of the 522 controls reported ever oral
      contraceptive (OC) use: the corresponding relative risk (RR) was 1.6 (95%
      confidence interval, CI, 1.2-2.2). The risk was restricted to ex-OC users (RR
      1.7, 95% CI 1.3-2.4), the estimated RR for current users being 0.9 (95% CI 0.5
      1.9). No clear relation emerged with duration, recency and latency of OC use and
      risk of endometriosis. In comparison with never IUD users, the risk for ever
      users was 1.3 (95% CI 0.6-2.8), and no clear relation emerged with duration of
      use. Likewise, no association was observed between barrier method of
      contraception and risk of endometriosis (RR ever vs never users 0.5, 95% CI 0.3
      1.4). The role of selection and other biases should be considered in the
      interpretation of epidemiological data on the role of OC on the risk of
      endometriosis.

PMID- 8137626
TI  - Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of
      use: a randomized comparative trial.
AB  - A 20 micrograms/24 hours levonorgestrel-releasing intrauterine contraceptive
      device (LNG-IUD) has, in an open randomized multicenter study, been compared to
      the copper-releasing device Nova T during 5 years of use; 1821 women had the LNG
      IUD and 937 women had the Nova T inserted. The 5-year cumulative gross pregnancy
      rate was 5.9% for Nova T and 0.5% for the LNG-IUD. The local effect of
      levonorgestrel in the uterine cavity causes reduction of menstrual blood loss and
      development of oligo-amenorrhea, and the termination rates because of heavy
      and/or prolonged menstrual flow were significantly (P < 0.001) lower among LNG
      IUD users. However, the gross termination rate because of amenorrhea was 6.0 in
      this group. Hb increased during use of the LNG-IUD and decreased during Nova T
      use, and the difference between the devices was statistically significant. The
      incidence of pelvic inflammatory disease (PID) was low in LNG-IUD users
      regardless of age, whereas in the Nova T group, the PID rate was increased among
      the youngest women, which makes the difference between the devices significant (P
      < 0.01). The gross termination rate for reasons considered to be hormonal was
      12.1 in the LNG-IUD group compared to 2.0 in the Nova T group (P < 0.001). The
      LNG-IUD is a long-acting reversible contraceptive method for 5 years with a
      pregnancy rate comparable to female sterilization. The incidence of PID is low
      even in young women. In addition, the positive health effects such as decreased
      menstrual blood loss and increased blood haemoglobin concentration make the LNG
      IUD a favorable combination of hormonal and intrauterine contraception.

PMID- 8137628
TI  - A multicentre clinical trial with RU 486 followed by 9-methylene-PGE2 vaginal gel
      for termination of early pregnancy: a dose-finding study. Indian Council of
      Medical Research Task Force on Hormonal Contraception.
AB  - A dose-finding study was carried out with two different doses of RU 486 (200mg or
      600mg) each in combination with two doses of 9-methylene-PGE2 gel (3mg or 5mg)
      for termination of pregnancy between 7 to 28 days after missed menstrual period.
      It was observed that the success rates with 200mg RU 486 followed by 5mg 9
      methylene-PGE2 gel were 94.5% and 89.6% in women with 7-14 days and 15-28 days of
      missed menstrual period, respectively. These rates were similar to those observed
      with 600mg RU 486 given along with 3mg or 5mg 9- methylene-PGE2 gel and were
      significantly higher than those observed with 200mg RU 486 given along with 3mg 9
      methylene-PGE2 gel. All subjects except four started bleeding following the
      treatment. The average duration of bleeding in subjects with successful outcome
      (complete abortion) ranged between 7.0 to 11.8 days in the four different
      treatment schedules. There were no serious side effects with any of the treatment
      schedules; only one subject required transfusion of one unit of blood for heavy
      bleeding. The immediate and delayed complication rates were similar with the four
      treatment schedules.

PMID- 8137627
TI  - Contraceptive use and attitudes in Great Britain.
AB  - In order to update current knowledge on contraceptive use and attitudes in Great
      Britain (i.e. England, Scotland and Wales), a survey was conducted among 1753
      randomly selected British women aged 15-45. Replies were received from 967 women
      (55.2%). Seventy-three percent (73%) of fertile, sexually active women who wished
      to avoid pregnancy were using reliable methods of contraception, viz. oral
      contraceptives (OCs), intrauterine devices (IUDs) or sterilization. However, it
      was found that adolescents and women over 40 who wished to avoid pregnancy were,
      nevertheless, especially likely not to be using any contraceptive method at all.
      The women surveyed were concerned about weight gain, cardiovascular and cancer
      risks associated with OC use, and infection and infertility risks associated with
      IUD use. Sixty percent (60%) perceived sterilization as a major and risky
      surgical operation. It was concluded that contraceptive practice in Britain had
      not improved greatly in recent years. The latest scientific findings regarding
      the true advantages and disadvantages of OCs, IUDs and sterilization, therefore,
      need to be brought to the attention of the lay public more effectively. Special
      efforts need to be directed towards providing adolescents and women over 40 with
      proper information. Physicians and the mass media could play a considerable role
      in this respect.

PMID- 8137629
TI  - The presence of two sites of action of endothelins in the isolated rabbit iris
      sphincter and dilator muscles.
AB  - The contractile activity of endothelins (ETs) and their effect on twitch
      contraction evoked by electrical field stimulation were studied in the isolated
      rabbit iris sphincter and dilator muscles using the isometric tension recording
      method. ET-1, ET-2 and ET-3 caused slow contractile response of the sphincter as
      well as the dilator muscles, with sphincter muscle EC50 values of 37.3, 58.0 and
      84.3 nM, and dilator muscle values of 31.7, 69.0 and 224.4 nM, respectively.
      These contractile responses were not affected by atropine (1 microM), prazosin (1
      microM) or indomethacin (1 microM). ET-1 and ET-3 slightly but significantly
      inhibited the fast cholinergic component of twitch contraction of the sphincter
      muscle evoked by field stimulation, without affecting the response to carbachol.
      However, ET-1 did not affect the slow substance P-ergic component of twitch
      contraction of this preparation. In the dilator muscle, ET-1 and ET-3 had little
      effect on the contraction induced by phenylephrine but reduced the amplitude of
      the twitch contraction evoked by the field stimulation. The inhibitory effect of
      ETs on the dilator muscle was antagonized by pretreatment with BQ-123 (100 nM),
      which is a selective ETA receptor antagonist. Pretreatment with indomethacin (1
      microM) also attenuated the inhibitory effect of ETs on the twitch contraction.
      These results suggest that ETs may have two sites of action, pre- and post
      synaptic effects, on the rabbit iris sphincter muscle as well as the dilator
      muscle. All three ET isopeptides may have direct contractile activity on the
      smooth muscles of the sphincter as well as the dilator without mediation by
      prostaglandins or neuronal mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137630
TI  - The human lens fiber-cell intrinsic membrane protein MP19 gene: isolation and
      sequence analysis.
AB  - DNA sequence analysis of overlapping shotgun and restriction fragments have
      revealed the entire sequence of the human lens fiber cell intrinsic membrane
      protein MP19 gene (also termed MP17, MP18, and MP20). The 8,056 bp MP19 gene
      contains 5 exons encoding a mature protein of 173 amino acids, which displayed a
      very high degree of identity (91%) with that of bovine MP19, deduced from a
      bovine cDNA sequence. The exon range in size from 52 bases (exon 1) to about 340
      bases (exon 5). The introns consist of two large segments (introns B and C) of
      about 4,700 bases and 1,800 bases, respectively, and two small segments (intron A
      and D) of about 450 and 250 bases each. Seven Alu family DNA repeats are found
      within the human MP19 gene. The sequenced gene includes 100 bases of 5' flanking
      sequence.

PMID- 8137631
TI  - Cytochrome oxidase activity in bovine and human retinal pigment epithelium:
      topographical and age-related differences.
AB  - Cytochrome c oxidase (CO) is a mitochondrial enzyme complex that was used in this
      study as a marker enzyme of aerobic metabolism. The activity of the enzyme was
      measured in the RPE of posterior and peripheral regions of bovine and human eyes.
      The posterior regions included the bovine area centralis or human macula. To
      determine if aging affected CO activity, activity was compared in RPE cells from
      human donors of varying age. An in vitro aging model was also used in which CO
      activity was measured in bovine and human RPE cells that were aged by repeated
      culture passage. CO activity was found to be significantly lower in posterior RPE
      cells from both bovine and human eyes suggesting that aerobic metabolism in RPE
      cells differs regionally. For human RPE samples, CO activity was lower in
      posterior cells at all donor ages and no significant age-related changes in CO
      activity were observed except that the highest activity samples were from older
      donors. Similarly, RPE cells that were aged in culture showed no significant
      changes in CO activity per cell although there were some high activity samples
      among the aged cultures. With aging, RPE cell density at confluency declined
      resulting in lower total CO activity in the aged epithelial monolayer. The data
      suggest that the ability of individual RPE cells to generate energy via
      respiration is maintained in the aged eye, but because RPE cell number declines
      with age and the activity of remaining RPE cells does not increase
      commensurately, there may declines in the ability of the aged pigment epithelium
      to perform tissue-level functions (e.g., transepithelial transport).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8137632
TI  - Cataract incidence and analysis of lens crystallins in the water-, urea- and SDS
      soluble fractions of Emory mice fed a diet restricted by 40% in calories.
AB  - Restriction of dietary calorie intake is associated with life extension and with
      the delay of age-related disorders. Preliminary studies demonstrated that by
      feeding the Emory mouse a diet restricted by 21% in calories cataract and
      insolubilization of protein could also be delayed. To observe the effects of
      calorie restriction over prolonged portions of adulthood, Emory mice were fed the
      control diet (C) or a diet restricted by 40% in calories (R). Feeding the R diet
      was associated with delayed formation or progress of cataract over virtually the
      entire second half of life. At 11 months of age, bilateral grade 5 cataracts were
      present in 17% and 2% of C and R lenses, respectively. At 22 months of age,
      bilateral grade 5 cataracts were present in 90% and 18% of C and R lenses,
      respectively. The distribution of alpha-, beta-, and gamma- crystallins in the
      water-soluble, urea-soluble, and SDS-soluble fractions indicates more
      similarities than differences between C and R lenses with a specific grade of
      cataract or of a given age. However, there were significant and abrupt (after
      grade 4 cataract) losses of particular gamma-crystallins; gamma-crystallins which
      were not prominent at earlier stages became the major gamma-crystallin moieties.
      Losses of alpha-crystallins were also noted upon cataract formation or aging in
      most of the fractions. Aggregates including gamma- and alpha-crystallins also
      accumulate faster in the C group.

PMID- 8137633
TI  - The fractal geometry of proliferative diabetic retinopathy: implications for the
      diagnosis and the process of retinal vasculogenesis.
AB  - 10 retinal vessel patterns with neovascularisation at or near the optic disk
      (NVD) from eyes of patients with diabetic retinopathy were compared with vascular
      patterns from 14 normal eyes. The vascular patterns were taken from low angle
      fundus photographs. After digitizing, the fractal dimensions were calculated by
      means of the density-density correlation function method. The fractal dimension
      was found to be significantly higher for vessel patterns with NVD [D = 1.845 +/-
      0.056 (m +/- sd)] as compared with the normal control group (D = 1.708 +/- 0.073)
      (p < 0.001). The fractal dimension of 1.8 appears to be a cutoff value. Higher
      values may indicate proliferative changes. Under these conditions the sensitivity
      of the method for the detection of NVD > or = Grade 3 in the Early Treatment
      Diabetic Retinopathy Study (ETDRS) grading system is 90%. The presence of such
      NVD in an eye is a "high risk characteristic" for severe visual loss, which
      requires panretinal laser treatment. Fractal analysis is therefore a possible new
      strategy for computer assisted "automated" detection and quantification of
      proliferative diabetic retinopathy. The fractal dimension of the new vessels
      suggests possible mechanisms involved in retinal vasculogenesis.

PMID- 8137634
TI  - Alterations in retinal Na+, K(+)-ATPase in diabetes: streptozotocin-induced and
      Zucker diabetic fatty rats.
AB  - The temporal pattern of changes in the specific activities of retinal Na+, K(+)
      ATPase (Na, K-ATPase) and Mg(2+)-ATPase (Mg-ATPase) were determined at several
      time intervals following the onset of diabetes in streptozotocin-induced diabetic
      (STZ: at 1, 2, 4 and 6 months) Long-Evans hooded rats, spontaneously diabetic
      Zucker diabetic fatty (ZDF: at 1, 2 and 4 months) rats and their age-matched
      controls. These animals were utilized as models for insulin-dependent diabetes
      mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM),
      respectively. Na, K-ATPase specific activity, using 10(3) M ouabain, was
      decreased (-6% to -14%) at all time points after the appearance of hyperglycemia
      in the ZDF rat, but was reduced only after 4 and 6 months in the STZ rat (-8% and
      -14%, respectively). In contrast, Mg-ATPase activity was significantly increased
      (13%) after 4 months in the ZDF rat and after 6 months in the STZ rat (8%). The
      concentration-dependent inhibitory effects of ouabain (10(-9) to 10(-3) M) on the
      activity of Na, K-ATPase in diabetic rats and age-matched controls was used to
      assess the time-dependent effects of diabetes on the alpha 3-high ouabain
      affinity or the alpha 1-low ouabain affinity retinal Na, K-ATPase isozymes. The
      retinal Na, K-ATPase activity for the alpha 3 isozyme was significantly lower at
      all times examined for the ZDF (-5% to -26%) and STZ-induced diabetic rats (-8%
      to -14%). This was reflected in the markedly decreased half-maximal inhibitory
      concentrations (IC50) of ouabain for the alpha 3 isozyme. For example, after four
      months of diabetes, the mean +/- SEM IC50 values were 12 +/- 3 nM in the STZ rats
      and 48 +/- 6 nM in the age-matched controls and 19 +/- 3 nM in the ZDF rats and
      30 +/- 4 nM in the age-matched controls. In contrast, the activity of the alpha 1
      isozyme was slightly, but significantly, decreased at 2 and 4 months in the ZDF
      rats (-4% to -7%) and after 4 and 6 months in the STZ-induced diabetic rats (-3%
      to -9%) while the IC50 values were unchanged. Moreover, the Hill coefficient for
      the alpha 3 isozyme was decreased in both diabetic groups while it was unchanged
      for the alpha 1 isozyme.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8137635
TI  - The effect of transforming growth factor-alpha (TGF alpha) on rabbit and primate
      lens epithelial cells in vitro.
AB  - TGF alpha, a member of the epidermal growth factor family stimulates
      proliferation of various cells. In the search for molecules that regulate cell
      division in the lens epithelium, the effect of numerous growth factors including
      EGF and FGF has been determined. In this study, the effect of TGF alpha on lens
      epithelial cells (LEC) from rabbit and monkey was investigated and compared to
      FGF and EGF. Since TGF alpha is suggested to be a factor that is regulated by
      auto and/or paracrine mechanisms, an immunohistochemical visualisation of the
      factor in the rabbit lens in situ was performed. TGF alpha stimulates LEC in a
      dose-dependent manner with a maximal threefold increase in cellular proliferation
      at 100 ng/ml. At a concentration above 10 ng/ml the cells lost their epithelial
      morphology and became irregular and star-shaped. Since TGF alpha is a potent LEC
      mitogen and has shown to increase in aqueous humour after trauma to the eye, this
      factor might be one of the molecules that regulate normal cell division in the
      ocular lens as well as LEC growth after cataract surgery.

PMID- 8137636
TI  - [Urinary minor proteins, beta 2-microglobulin (beta 2-MG) assay with pregnancy
      induced hypertension (PIH)].
AB  - Urinary minor protein (Alb, IgA, IgG, IgM) contents were determined by ELISA
      method and beta 2-MG were determined by Radioimmuno Assay (RIA) method in 50
      patients with PIH and in 50 normal pregnant women. It was showed that A1b in all
      patients with PIH was significantly increased than that of the normal control (P
      < 0.001). There was a significantly difference of urine IgA, IgG, IgM in each
      type of PIH (P < 0.05). Serum beta 2-MG level was significantly increased in
      patients with severe PIH, (P < 0.001) and it was positively correlated with serum
      uric acid. This study indicated that the combination of ELISA and RIA may be
      helpful to understand both the location and severity of lesion in the kidney with
      PIH.

PMID- 8137637
TI  - [Plasma endothelin levels in pregnancy induced hypertension].
AB  - Plasma endothelin level (ET) was measured by radioimmunoassay in 10 healthy non
      pregnant women, 10 normal pregnancies, 41 cases with pregnancy induced
      hypertension (PIH), and in cord plasma of 19 normotensive and 14 PIH women as
      well. There was no significant difference of ET levels between non-pregnant and
      normal pregnant women (P > 0.05). On the contrary, ET value in PIH was
      significantly higher than that in normal gravida (P < 0.01) and it was positively
      correlated with the severity of PIH. The mean value of ET in mild, moderate and
      severe PIH were 2.58 x 10(-8) mol/L, 4.08 x 10(-8) mol/L and 4.53 x 10(-8) mol/L,
      respectively. ET of umbilical vein (UV) in normal pregnancy was 4 times higher
      than that from the mother, while it was 2 times higher in PIH situation. The
      findings in this study suggested that ET may be contributed to the vasospasm
      associated with PIH and might be one of the factors that caused the pathogenesis
      of PIH. The high concentration of ET in UV may play a role in fetal hemodynamic
      changes.

PMID- 8137638
TI  - [Changes in blood visco-elasticity in normal pregnancy and pregnancy induced
      hypertension].
AB  - The study was designed on blood visco-elasticity of normal pregnant and pregnancy
      induced hypertension (PIH) women. Visco-component (eta'), elastic-component
      (eta") and storage modulus (G') decreased significantly during the 1st trimester
      of pregnancy, but rose slowly in the 3rd trimester. eta' was the most significant
      and it revealed an inverse correlation with neonate birth weight. There were no
      changes of eta', eta" and G' in women with mild PIH, but they rose markedly in
      groups with moderate and severe PIH. In conclusion, abnormal blood viscosity and
      elasticity, i.e. an increase of RBC aggregation and/or a decrease of RBC
      deformability, may be an important abnormal hemorheological changes in PIH.

PMID- 8137639
TI  - [Placental pathology in gestational diabetes].
AB  - To observe the influence of gestational diabetes over placental morphology, a
      prospective study was taken for 28 gestational diabetic pregnancies and 25 non
      diabetic control subjects. Placental net weight in diabetic group is 549.38 +/-
      143.01 g; in control group 458.75 +/- 60.98 g, significant difference was found
      between above two groups. The changes of diabetic placentas in light microscopy
      shows villous immaturity, proliferation of small fetal vessels,
      syncytiotrophoblast knots, cytotrophoblast and vessel syncytiotrophoblast
      membrane increased. Morphohistometric investigations showed that the changes of
      placenta in gestational diabetes are significant.

PMID- 8137640
TI  - [Bacteria condition of low genital tract of pregnant women and neonatal
      infection].
AB  - The swab from low genital tract of 74 cases of pregnant women, which were
      selected at random, were taken in labour and delivery room before delivery. A
      piece of placenta tissue and the swab of neonatal respiratory tract were obtained
      after delivery and were cultured in anaerobic and aerobic condition within 24
      hours. Thirty-eight percent of bacteria that cultured in neonatal respiratory
      tract were the same species that obtained from maternal low genital tract and
      placentae. There were 15 infected neonates from 74 neonates, with positive
      culture in 9 neonates. Staphylococcus aureus played an important part in neonatal
      infection. Sixty seven percent of bacteria from the infected neonates were
      similar to the bacteria detected in low genital tract and placentae. Vertical
      transmission may play an important role in neonatal infection.

PMID- 8137641
TI  - [The change in dynamics of cell proliferation cycle by passive smoking in fetal
      rabbit].
AB  - An animal model of IUGR was induced in rabbit by passive smoking. The dynamics of
      cell proliferation cycle in fetal brain, liver and placenta was analysed by flow
      cytometry. The results showed that the ratio of cell number in phase G0+G1 to the
      total number of cells in all phases was increased, while the cell number in phase
      S+G2M to the total cell number of all phases was decreased. It means that the
      proliferation of fetal cell and placenta was inhibited significantly. The actual
      inhibition was occurred in the phase of transformation from phase G1 to S.

PMID- 8137642
TI  - [Gamete donation in an in vitro fertilization program].
AB  - Two cases of gamete donation in an IVF program were reported in this paper. In
      the first case the wife with recurrent abortions was found to have chromosomal
      abnormality, her karyotype was 45,XX,-14,-14 + rob (14 Q 14 Q). She became
      pregnant after IVF-ET with donated ova, and was delivered of a normal male baby
      on June 12, 1992. The baby's karyotype was normal. The blood group of both the
      husband and wife was O, while that of the baby was B. The baby suffered from
      icterus neonatorum as a result of ABO incompatibility but recovered quickly after
      treatment. Further DNA finger print analysis of the husband, wife and baby,
      combined with the history of egg donation IVF, proved the relationship of the
      parents with the baby. In the second case the husband's karyotype was 46,XY, t(4;
      9) (4Q+; 9Q-). The wife had also history of recurrent abortions. Since 1989, the
      wife received sperm donation IUI 5 times in another hospital without success. IVF
      ET with donated sperms was performed in November 1991 resulting in clinical
      pregnancy. She was delivered of a pair of twins, one male and one female on July
      20, 1992. The possibilities of different types of gamete formation during meiosis
      in carriers of chromosomal balanced translocation were briefly discussed.
      Donation of oocytes could be realized only in an IVF program, which is also the
      only way to propagate for the family. However, IVF with donated sperms is
      indicated in women with blocked tubes besides the male factor or after repeated
      failures of other assisted reproductive technologies.

PMID- 8137643
TI  - [Atypical hyperplasia and complex hyperplasia of endometrium in women of
      reproductive age].
AB  - The initial and follow-up endometrial curettings from 17 patients with atypical
      hyperplasia (AH) and 4 patients with complex hyperplasia (CH) were reviewed. All
      cases were younger than 40 years and the duration of follow-up ranged from 7
      months to 38 years (mean, 11.3 years). According to the ISGP classification, the
      histological diagnostic criteria based solely on the presence of cytologic
      atypia. Twenty of them received progestin treatment and the lesion regressed at
      some time, but relapsed eventually. Twelve of them were performed hysterectomy
      after repeat progestin administrations and only 2 (11.8%) of 17 patients with AH
      progressed to invasive carcinoma 6 to 8 years later; however, all 4 patients with
      CH and 2 patients with milder forms of AH became pregnant and had normal term
      deliveries during the follow-up period. The histological diagnosis, prognoses and
      the effects on fertility in patients with AH and CH are discussed.

PMID- 8137644
TI  - [Gonadal tumor and Y chromosome].
AB  - The histologic features of gonads occurrence of gonadal tumor, and RIA
      reproductive hormone levels in 50 cases containing a Y chromosome karyotype were
      analysed. The correlation between gonadal tumor and Y chromosome, clinical
      manifestation and genotype, and the principle of diagnosis and treatment are
      discussed. There were seven cases of gonadal tumor in these fifty cases the
      frequency of gonadal tumor is 14% (7/50). All of them were present in cases with
      gonadal dysgenesis, with the frequency rate of 27% (7/26). Five cases were
      bilateral, and two were unilateral, that made a total of twelve tumors in these
      seven cases. Gonadoblastoma was type of tumor commonly found, about 75% (9/12).
      The above date suggested that there is a higher frequency of gonadal tumor in
      cases of gonadal dysgenesis with a Y chromosome. Both hypergonadotropins and low
      sex steroids levels were the feature of gonadal dysgenesis, but no relative with
      occurrence of the tumor. The phenotype of these fifty cases were largely due to
      the process of abnormal sexual differentiation not only depend on the sex
      chromosome complement. In treatment, prophylactic bilateral gonadectomy is
      emphasized.

PMID- 8137645
TI  - [Relation between DNA content in ovarian cystadenoma and its pathohistology].
AB  - DNA index and cell cycle distribution were studied by flow cytometry in 32 cases
      of ovarian borderline cystadenoma, 16 ovarian cystadenocarcinoma and 12 ovarian
      benign cystadenoma, and their relations to pathological patterns of the diseases
      were inquired. The results showed that the DNA index and S+G2M phase in cell
      cycle of the diseases were related to their pathological patterns. The DNA index
      and S+G2M cell were increased by turn from benign to borderline and to malignant
      tumor. DNA index and cell cycle distribution might be valuable in reflecting the
      biological behavior of deteriorating ovarian cystadenoma. The authors consider
      that determination of DNA content and cell cycle could be biological indexes of
      supplementary diagnosis for the deterioration of borderline tumor.

PMID- 8137646
TI  - [Clinical evaluation of ultrasonography in diagnosis of the early invasive
      hydatidiform mole].
AB  - The consecutive uterine changes of the B ultrasonic scan were observed in 41
      cases with invasive hydatidiform mole, which compared with the uterine changes in
      10 controls who had induction of labor in second trimester. It was found that B
      ultrasonic scan was very useful technic in diagnosis of invasive mole. The time
      when the serum hCG titers fell to normal was earlier than the time of B scan
      reversed during treatment. Therefore, the B scan of uterus is of value in early
      diagnosis and therapeutic quide of invasive mole.

PMID- 8137648
TI  - [Pregnancy and acquired immunodeficiency syndrome].

PMID- 8137647
TI  - [Effect of sodium prasterone on termination of mid-trimester pregnancy].
AB  - Sodium prasterone sulfate was used before termination of mid-trimester pregnancy
      in 50 cases, and another 50 cases taking no drug as the control group. Both
      groups were given intraamniotic rivanol. In the treatment group, the results
      indicated that the Bishop score was elevated by 1 to 8. There were an effective
      rate of 86% and satisfactory rate of 98%. In comparison, the control group showed
      40% (P < 0.001) and 76% (P < 0.01) respectively, and there was significant
      difference between the 2 groups. The average induction-abortion time interval was
      13.2 hours shorter in treatment group (P < 0.01). Adverse effects such as nausea
      or fatigue was only seen occasionally.

PMID- 8137649
TI  - [Advance in immunoadsorption therapy].

PMID- 8137650
TI  - [Computerized tomography of liver in alveolar echinococcosis treated with
      albendazole].
AB  - Eleven cases of alveolar echinococcosis were examined by using computerized
      tomographic (CT) scanning of liver 2-7 years after long-term continuous
      albendazole therapy. In seven cases the hepatic lesion was almost completely
      calcified and cured in three cases incomplete calcification of the peripheral
      margin of the hepatic lesion was observed. CT scanning of the remaining in
      effective case showed active lesion with heterogenous hypodense areas in the
      liver without calcification on the peripheral margin. Long-term continuous
      albendazole therapy can be lethal to the parasite.

PMID- 8137652
TI  - [Factors influencing the prognosis of gastric cancer patients: a study using
      international gastric cancer staging classification].
AB  - In the 18-year period from 1973 to 1991, 502 cases with gastric cancer were
      treated surgically at the Peking Union Medical College Hospital. A unified
      international classification for staging of gastric cancer had been applied to
      these patients in this study. The pathologic staging classification is based on
      the extent of the disease at the time of surgical exploration of the abdomen
      and/or histopathologic study of the excised surgical specimens. According to the
      new TNM staging classification, the 5-year cumulative survival rates of all
      surgically treated patients Ia, Ib, II, IIIa, IIIb and IV were 96.25%, 87.34%,
      66.11%, 43.70%, 30.33% and 9.36% respectively. It was showed that there is a
      decreasing tendency in the 5-year survival rates for the depth of invasion of the
      gastric cancer. The histological types of the gastric cancer had the same
      prognostic significance as depth of invasion. The 5-year cumulative survival rate
      of patients with curative surgery was better in the group with chemotherapy
      (55.6%) than in that without chemotherapy (43%).

PMID- 8137651
TI  - [Comparison of dipyridamole Tc-99m myocardial imaging with dipyridamole
      electrocardiogram in detecting coronary artery disease].
AB  - The authors compared the results of dipyridamole myocardial-SPECT (D-ECT) with
      dipyridamole electrocardiogram (D-ECG) in detecting coronary artery disease
      (CAD). According to the result of coronary artery angiogram. We analysed the
      results of D-ECT and D-ECG in 62 patients. In detecting CAD, the sensitivity and
      specificity of D-ECT were 89%, and 92%, while those of D-ECG were 54% and 76%
      respectively. In detecting single double, triple vessel diseases, the sensitivity
      of D-ECT was 76%, 100% and 100% respectively. The sensitivity of D-ECG was 35%,
      73% and 67% respectively. In identifying left anterior descending, left
      circumflex and right coronary artery, the sensitivity of D-ECT was 73%, 80% and
      80% respectively, while that of D-ECG was 54%, 20% and 25% respectively. The
      results showed that D-ECT was better than D-ECG in diagnosing CAD.

PMID- 8137653
TI  - [A long-term follow-up study with endoscope in chronic gastritis].
AB  - A 10 to 17 years endoscope follow-up was performed to 138 cases of chronic
      gastritis. The result showed that 118 cases still proved to be chronic gastritis,
      and the increase of chronic atrophic gastritis (CAG) in numbers. 15 cases
      developed into peptic ulcer. 5 cases to carcinoma (4 cases were early carcinoma).
      The time of cancerization differed from 2 to 12 years. The rate of cancerization
      of CAG reached 7.46%. The rate of cancerization of intestinal metaplasia (IM)
      were 8.20%. 13 cases of IM were mucus histo-chemical stained, and five of them
      contained sulfuric acid mucus, one of the 5 cases cancerized. 3 of 14 cases with
      atypical hyperplasia (ATP) turned into stomach cancer. We believe that chronic
      gastritis, especially CAG with ATP and IM, or with sulfuric acid mucus of IM had
      a high possibility of cancerization with the increase of age, and should be
      followed up for a long time.

PMID- 8137654
TI  - [Changes of immunologic function in patients with COPD induced chronic cor
      pulmonale].
AB  - We determined the counts of lymphocyte subpopulation CD3+, CD4+, CD8+ and CD16+
      in PBL by using APAAP method and some humoral immunological parameters (HIP) in
      patients with COPD induced chronic cor pulmonale. The results showed: (1) In
      cases during exacerbation stage, the counts of CD3+, CD4+, CD16+ and the
      CD4+:CD8+ ratio decreased remarkably (P < 0.001). There was significant
      correlation between the counts of CD3+, CD4+, the CD4+:CD8+ ratio and PaO2 (P <
      0.01). No marked change in serum IgG, IgA and IgM level was observed. Serum IgE
      and CIC level was significantly higher and C3 level lower than those in controls
      (P < 0.01). After treatment the counts of CD3+, CD4+, CD16+ and the CD4+:CD8=
      ratio went up notably (P < 0.01), but no significant change was found in the HIP.
      (2) In cases during remission stage only the CD4+ level was low (P < 0.05) and no
      remarkable difference was observed in the HIP. After treatment with thymopeptide
      the counts of CD4+ increased (P < 0.05), CD8+ decreased (P < 0.01) and the
      CD4+:CD8+ ratio increased (P < 0.01). The serum IgA and CIC level also went up
      significantly (P < 0.05). This indicated that thymopeptide played a role in
      regulating the immunologic function.

PMID- 8137655
TI  - [The effect of cyclooxygenase and thromboxane synthetase inhibition on oxygen
      metabolism in canine acute respiratory failure].
AB  - The purpose of this study is to evaluate the effect of cyclooxygenase inhibitor
      and thromboxane synthetase inhibitor on oxygen metabolism in acute respiratory
      failure. Acid aspiration was induced in 18 dogs. Six dogs were pretreated with
      ibuprofen (IBU), six with OKY-046 (OKY), and the remaining six used as control.
      After acid aspiration oxygen delivery (DO2) fell in all groups as a result of
      decreased PaO2 and cardiac output. However, oxygen consumption (VO2) was
      maintained in all animals by the end of the experiment except in the control
      group. Arterial oxygen content was maintained at baseline level throughout the
      experiment in IBU group. Meanwhile a significantly decreased mixed venous oxygen
      tension was found in OKY group after acid challenge. Linear regression of VO2 and
      DO2 was confirmed in both the control and OKY groups. However, the dependent
      relationship between VO2 and DO2 was not identified in IBU group; this may
      indicate that the body oxygen metabolism was maintained rather well in acute
      respiratory failure dogs treated with ibuprofen.

PMID- 8137656
TI  - [Comparison of quality of life in continuous ambulatory peritoneal dialysis and
      hemodialysis patients].
AB  - Quality of life is a important outcome of treatment of chronic disease. It's also
      a major factor to determine the selection of various modes of therapy for end
      stage renal diseases (ESRD) patients. Quality of life may be influenced by some
      case mix factors. 17 continuous ambulatory peritoneal dialysis (CAPD) patients
      and 17 hemodialysis patients were closely matched on sex, age, initial disease,
      education, financial support, cormidity and marital status to compare their
      quality of life. There were no difference of quality of life between these two
      group. These results suggest that dialysis modality do not likely to exerts an
      independent effect on quality of life of chronic dialysis patients. It may be
      warrant to speed up the CAPD program due to its less expensive.

PMID- 8137657
TI  - [Relationship between obesity and risk factors of coronary heart disease in
      nondiabetics].
AB  - We analysed the data of 395 nondiabetic obese (BMI 25-42.2, impaired glucose
      tolerance, IGT, 257 and normal glucose tolerance, NGT, 138) and 482 nonobese
      subjects (BMI 15.9-24.9, IGT 170 and NGT 312). The blood pressure, plasma
      glucose, insulin, triglyceride and total cholesterol in obese were higher than
      that in nonobese, while HDL-c level was lower after controlling for age and sex
      (P < 0.001). This difference remained to be significant even after the adjustment
      of age, sex, insulin and 2-hours plasma glucose. Therefore, it was suggested that
      obesity was easy of access to coronary heart disease risk factors independent of
      hyperglycemia and hyperinsulinemia.

PMID- 8137658
TI  - [Effect of parathyroidectomy (PTX) on aluminum (Al) induced bone disease].
AB  - Al-treated or untreated decalcified sections of bone matrix were implanted
      subcutaneously into the abdominal wall of parathyroidectomized (PTX) or control
      rats for 21 or 28 days. The bone remodeling and Al, Ca content in the implants
      were measured by using histomorphometry and atomic absorption spectrum method.
      The results showed that bone area, osteoclast number, osteoblast number and bone
      mineralization rate of Al-treated or untreated bone in PTX rats and of Al-treated
      bone in control rats were significantly lower than those of untreated bone in
      control rats (P < 0.05). There was no marked difference between these parameters
      of Al-treated bone in control rats and untreated bone in PTX rats (P > 0.05), and
      these of Al-treated bone in PTX rats were the lowest (P > 0.05- < 0.05). Ca
      contents were consistent with the histological parameters. Bone Al removing rate
      between PTX and control rats was not markedly different. In conclusion, both PTX
      and Al impair bone formation and mineralization, bone biopsy and removal of Al
      from bone is necessary before PTX treatment in uremic patients with secondary
      hyperparathyroidism.

PMID- 8137659
TI  - [Relationship between colorectal cancer and ten inorganic elements].
AB  - A population-based case-control study including 726 patients with colon cancer,
      575 with rectum cancer, and 1400 population controls matched on age (+/- 5 yrs.)
      and sex was carried out to evaluate the association of ten inorganic elements,
      including potassium, sodium, calcium, magnesium, iron, manganese, zinc, copper,
      phosphorus and selenium, and other dietary factors with colorectal cancer. Single
      variable analysis adjusted for age and sex showed most of the ten elements,
      except sodium and selenium, may reduce the risk of the development of colorectal
      cancer. Correlation analysis indicated these eight elements correlated closely to
      the "vegetable factors", e.g., dietary fibre, and so on, since the major sources
      (about 80%) of these elements were from vegetables. Multi-variable logistic
      regression analysis showed nine elements (except sodium) may confound the effects
      of some dietary factors (such as dietary fibre and vitamin C) on the occurrence
      of colorectal cancer and only contribute to it. The results showed a close
      association between saturated fatty acid, mono-unsaturated fatty acid, dietary
      fibre, vitamins C and E, and colorectal cancer.

PMID- 8137660
TI  - [Experimental study on prevention of the colorectal cancer by China medical stone
      and the organgermanium compound].
AB  - To compare the effect of cancer prevention of China medical stone (CMS) and Ge
      132, rats were subcutaneously injected with dimethylhydrazine for 15 weeks and
      orally administered with 10% china medical stone soak and Ge-132 for 27 weeks.
      Colorectal cancer incidence in CMS was found significantly lower than in Ge-132
      and controls (P < 0.05-0.01). In Ge-132 only the mean cancer foci and the mean
      cancer volumes/rat were found significantly less than controls (P < 0.01). It was
      shown by endoscopy that a precancerous lesion of the bowel resulted from
      carcinogen was more mild in CMS and Ge-132 than in controls. Serum gamma
      interferon titer and NK activity of spleen cells were significantly elevated in
      CMS and Ge-132. Researches explained that the effect of cancer prevention of CMS
      was better than that of Ge-132.

PMID- 8137661
TI  - [Biochemical and toxicological studies of fenvalerate on the lung].
AB  - Toxicological effects of fenvalerate on rat lungs by bronchoalveolar lavage (BAL)
      and biochemical changes in 20 workers exposed to fenvalerate were studied. The
      results showed that the levels of CPK, albumin, TP, AKP, ACP, alpha 1-AT, MDH,
      LDH, glucose, and lactic acid in BAL fluid increased significantly, with a CPK
      level the most sensitive one. most of the above parameters in BAL fluid changed
      four hours after exposure and returned basically to normal on the fourth day
      after exposure. Only the levels of ACP, alpha 1-AT and albumin were found
      increased in their blood. It showed a good linear relationship between blood and
      BAL levels of alpha 1-AT and ACP. Changes in some biochemical parameters were
      also found in workers exposed to fenvalerate, which correlated to the length of
      their employment. The results suggested inhalation of fenvalerate may cause
      alveolitis, pulmonary edema, and damage to lung cells.

PMID- 8137663
TI  - [Relationship between step test index and maximal aerobic capacity in female
      adolescents].
AB  - The change pattern of step test index (STI) in female adolescents and its
      relationship with their maximal aerobic capacity were studied. Two hundred and
      thirteen girls aged 10 to 19 participated in the study. The physical and
      functional characteristics of the girls with higher STI scores were compared with
      those with lower ones. STI scores declined with age due to their increasing ratio
      of weight-to-height during puberty. The maximal aerobic working capacity was
      estimated by multiple regression analysis with the Quetelet Index (weight/height
      x 100) into the equation, and its accuracy of the prediction improved.

PMID- 8137662
TI  - [The effects of rapid entry into plateau on SODs and LPO levels in rats].
AB  - The activities of CuZn-SOD and Mn-SOD in rat plasma and liver dropped (P < 0.05
      and P < 0.01, respectively) but LPO levels increased significantly (P < 0.01)
      after the rats were got into plateau from plain rapidly. The decrease of the
      activities of SODs was associated with the rise of LPO levels. The results
      suggested that the formation of free radicals in the body increased and the
      antioxidant ability lowered after their rapid entry into plateau from plain, and
      it was unfavourable to their acclimatization to plateau.

PMID- 8137664
TI  - [Advances in research on dietary fibers].

PMID- 8137665
TI  - Together we will do it.

PMID- 8137666
TI  - Use of laparoscopic techniques in colorectal surgery. Preliminary study.
AB  - PURPOSE: This study evaluated the feasibility and safety of laparoscopic bowel
      surgery performed by colorectal surgeons not previously experienced in
      laparoscopic biliary or appendiceal surgery. METHODS: Thirty-two patients
      underwent ileocolic resection/anastomosis (n = 12), loop ileostomy (n = 7),
      colostomy (n = 4), ileostomy takedown/ileorectal anastomosis (n = 3), subtotal
      colectomy/ileorectal anastomosis (n = 2), sigmoid resection (n = 2), or other
      procedures (n = 2). No curative cancer surgery was undertaken. RESULTS: Time to
      first bowel movement was one to eight (median, four) days. Length of stay ranged
      from 4 to 11 (median, 6) days. There were no major complications seen in follow
      up from 6 to 15 (median, 7) months after surgery. CONCLUSIONS: Large intestinal
      and distal ileal surgery using laparoscopic techniques, performed by surgeons
      with training only in laparoscopic intestinal surgery, is feasible and safe.
      Faster recovery and need for less postoperative analgesia in laparoscopic surgery
      compared with conventional surgery cannot be surmised from this study. A
      randomized study design is needed to evaluate many of the differences between
      conventional and laparoscopic intestinal surgery.

PMID- 8137667
TI  - Distribution of metastatic lymph nodes in colorectal cancer by the modified
      clearing method.
AB  - PURPOSE: The aim of this study was to clarify the distribution of lymph node
      metastasis in colorectal cancer. We also examined the relationship between the
      primary tumor (T) and the regional node (N) categories of the TNM (primary tumor,
      regional nodes, metastasis) classification. METHOD: Lymph nodes of surgical
      specimens in 311 consecutive patients with colorectal cancer were studied using
      the modified clearing method. RESULTS: Lymph node metastasis was seen in 59.2
      percent of the total cases. The upward metastasis rate was 30.7 percent. In the
      longitudinal spread, most of the lymph node metastasis was seen within 10 cm. On
      the oral side in rectal cancer, there was no metastasis beyond 4 cm. The lateral
      metastasis rate in rectal cancer was 8.8 percent and in the lower rectum, the
      rate of cancer within 6 cm from the anal verge or beyond pT3 was much higher.
      CONCLUSION: In the TNM classification, there was no significant difference
      between colon and rectal cancer except pT1 with rectal cancer. In the lower
      rectal cancer within 6 cm from the anal verge or beyond pT3, there is a high risk
      of lateral metastasis, and lateral lymph node dissection or radiation therapy
      should be performed.

PMID- 8137668
TI  - Ileal pouch-anal anastomosis: is preoperative anal manometry predictive of
      postoperative functional outcome?
AB  - PURPOSE: The aim of this study was to determine the value of preoperative anal
      manometry in predicting post-operative continence. METHODS: Anal manometry was
      performed in 73 consecutive patients before ileal pouch-anal anastomosis (IPAA)
      surgery (m1), before loop ileostomy closure (m2), and at a follow-up of one (m3)
      and two (m4) years. Mean and maximum resting and squeezing pressures were
      documented at each occasion. One year after surgery, pressures were correlated
      (r) with an incontinence score. RESULTS: A significant (P < 0.05) decrease in
      mean resting pressures was observed after IPAA (m1 = 66 mmHg; m2 = 42.8 mmHg),
      followed by a significant (P < 0.05) improvement of mean resting pressure after
      loop ileostomy closure (m3 = 53.8 mmHg; m4 = 54.7 mmHg). Mean squeezing pressures
      did not change (P > 0.05) at any time during the study (m1 = 114 mmHg; m2 = 102.9
      mmHg; m3 = 103.4 mmHg; m4 = 95.8 mmHg). There was no correlation between
      preoperative mean resting pressure and postoperative (mI) incontinence score.
      CONCLUSION: Anal manometry showed a characteristic trend in internal anal
      sphincter injury after IPAA followed by recovery after ileostomy closure.
      However, it failed to prove helpful in the prediction of clinical outcome. Thus,
      although this study supports the continued use of manometry in a research
      setting, it challenges the value of routine manometry in a clinical context.

PMID- 8137669
TI  - Bisacodyl reduces the volume of polyethylene glycol solution required for bowel
      preparation.
AB  - PURPOSE: This study was designed to compare the efficacy and patient tolerance of
      standard orthograde bowel preparation using 4 liters of polyethylene glycol
      solution with only 2 liters of polyethylene glycol preceded by the stimulant
      laxative bisacodyl. METHODS: Three hundred eighty-two consecutive patients
      undergoing outpatient colonoscopy under two surgeons over a six-month period were
      randomized to receive one of the two preparations. Patients were asked to record
      the effects of the preparation and to give it a "discomfort rating" on a scale
      from 1 to 5. Surgeons were blinded to the preparation used and rated the quality
      of bowel cleansing on a scale of 1 to 5. One hundred ninety-one patients were
      randomized to the 4-liter preparation and 191 to the 2-liter preparation.
      RESULTS: Ninety-three percent of patients in the 2-liter group drank all of the
      solution as opposed to only 66 percent of patients in the 4-liter group. Patients
      in the 4-liter group gave the preparation significantly lower comfort scores than
      those in the 2-liter group (Fisher's exact test; P = 0.0001). The quality of
      bowel cleansing was not significantly different between the groups (P = 0.88). A
      total of 6.8 percent of the 2-liter group and 9.4 percent of the 4-liter group
      were considered by the surgeon to have had a poor preparation (rating 4 or 5).
      The quality of the preparation was found to correlate with the patients' age and
      compliance with the preparation regimen, and was found not to correlate with
      presenting symptoms, pathology, or a previous colonic resection. CONCLUSION:
      Bowel preparation with bisacodyl and 2 liters of polyethylene glycol is more
      acceptable to patients than a 4-liter regimen and is equally effective in
      cleansing the colon.

PMID- 8137670
TI  - Anal endosonography in healthy subjects and patients with idiopathic fecal
      incontinence.
AB  - PURPOSE: This study investigates the normal ultrasonographic morphology of pelvic
      floor striated muscle and evaluates whether there are differences between males
      and females and between healthy subjects and patients with idiopathic fecal
      incontinence. METHODS: Manometric and ultrasonographic studies of the anal canal
      were performed in 30 healthy volunteers and in 26 patients with idiopathic fecal
      incontinence. Verification of ultrasonographic findings was obtained by studying
      anatomic preparations. RESULTS: Ultrasonography reliably identified the internal
      and external anal sphincter and frequently visualized neighboring structures. In
      addition, it detected muscular structures that have not clearly been described
      previously. However, differences in external sphincter function between males and
      females and between healthy subjects and incontinent patients were not reflected
      by alterations in muscle thickness. CONCLUSIONS: Endosonography of the anal canal
      clearly delineates muscular structures and may even visualize structures that
      have been previously incompletely defined. However, it remains to be shown that
      differences in certain muscular functions have a morphologic correlate that can
      be detected by endosonography.

PMID- 8137671
TI  - Reversal of Hartmann's procedure: effect of timing and technique on ease and
      safety.
AB  - PURPOSE: The optimal time for reversal of Hartmann's procedure is controversial.
      Significant operative difficulty and morbidity have been reported for Hartmann's
      reversal. The purpose of this study was to examine 11 years' experience with
      Hartmann's reversal, with particular attention to rate of reversibility,
      operative difficulty, and timing of reversal. METHODS: Case records of all
      patients undergoing either Hartmann's procedure or Hartmann's reversal at St.
      Vincent's Hospital between 1981 and 1991 were examined. Patients having
      Hartmann's reversal were divided into an early group (before 15 weeks) and a late
      group (after 15 weeks). These groups were compared in terms of morbidity and
      mortality, bed stay, and operative difficulty. RESULTS: Hartmann's procedure was
      performed on 111 patients, mostly for advanced cancer and complicated
      diverticular disease. Of 96 patients who survived, 50 (52 percent) underwent
      reversal. Of those with diverticular disease, 40 of 48 (83 percent) underwent
      reversal. Mortality for Hartmann reversal was 2 percent; anastomotic leak rate 4
      percent; and overall complication rate 26 percent. Early reversal was performed
      in 13 patients and late reversal in 37 patients. There was no difference between
      these groups in mortality, morbidity, or anastomotic leakage. However, bed stay
      was longer in the early group and graded operative difficulty greater. In
      particular, cases in which adhesion density was most severe and in which
      accidental enterotomy occurred were more common in the early group (P = 0.02,
      Miettinen's modification of Fisher's exact test). CONCLUSIONS: Hartmann's
      reversal can be performed with an acceptable morbidity and mortality in most
      survivors of complicated diverticular disease. Operative difficulty appears to be
      less after a delay of 15 weeks.

PMID- 8137672
TI  - Anterior rectocele: assessment with radiographic defecography, dynamic magnetic
      resonance imaging, and physical examination.
AB  - PURPOSE: The aim of this study was to devise a measuring method for an anterior
      rectocele on standardized defecographies and magnetic resonance images (MRI) to
      quantify anterior rectocele and to test whether this could substantiate clinical
      decision making for operative treatment for anterior rectocele. METHODS:
      Quantitative analysis by the measuring method as proposed was compared with
      qualitative scores on defecographies and MRI from the same patients. Thirty-eight
      patients with symptoms compatible with an anterior rectocele were subjected to
      physical examination in the left decubitis position and supine position and to
      defecography. Findings on defecography were compared with findings on physical
      examination. Thirteen patients were examined before and after surgical correction
      of the anterior rectocele for a total of 51 qualitative and quantitative
      examinations. The group of operated patients was analyzed for treatment results.
      Nineteen controls were included. RESULTS: Sixty-six radiographs of 33
      defecographies were qualified in three grading classes and quantified with the
      proposed method by two observers. The mean measured value of the anterior
      rectocele in the three subjective grading classes is significantly different (P <
      0.001). Anterior rectoceles qualified as severe had a measured value of 20 mm or
      more in 96 percent of the radiographs. Lower gradings were never > 20 mm. On MRI
      severe anterior rectoceles were not scored and measured values did not correlate
      with qualitative scores. When findings on physical examination were compared with
      defecographic measurement, the coefficient of correlation (r) between the
      radiologic assessment and clinical examination in the left decubitis position is
      r = 0.87, for the examination in the supine position, r = 0.77. All 15 cases
      scored as severe anterior rectocele in the left decubitis position had a measured
      anterior rectocele of > or = 20 mm. In the 13 cases that received surgery, there
      was a significant reduction of the anterior rectocele (P < 0.001) and clinical
      improvement. Patients with small or moderate anterior rectocele on physical
      examination with a size > or = 20 mm on defecography were cured by surgical
      correction. None of the controls had an anterior rectocele on physical
      examination or an anterior rectocele > or = 20 mm on defecography. CONCLUSIONS:
      An anterior rectocele with a size of 20 mm or more corresponds with a qualitative
      score of "severe" on radiographic defecography. Physical examination for anterior
      rectocele in the left decubitis position corresponds best with quantitative
      radiographic assessment and anterior rectocele with a size > or = 20 mm on
      defecography is pathologic. Patients with complaints compatible with anterior
      rectocele can be assessed in objective and quantitative terms by radiography and
      can be successfully surgically treated, even if at physical examination the
      anterior rectocele is not classified as large, provided that dynamic defecography
      shows an anterior rectocele of > or = 20 mm. The potential of dynamic MRI with
      regard to anterior rectoceles presently seems absent.

PMID- 8137673
TI  - Use of doxorubicin and dacarbazine for the management of unresectable intra
      abdominal desmoid tumors in Gardner's syndrome.
AB  - PURPOSE: The aim of this study was to describe the natural history and management
      of surgically unresectable intra-abdominal desmoid tumors in two patients with
      Gardner's syndrome from two unrelated families, where each had failed on
      conventional therapy. METHODS: Two patients with Gardner's syndrome were placed
      on a chemotherapy regimen which included doxorubicin (90 mg/m2) and dacarbazine
      (900 mg/m2) in divided doses over four days of continuous infusion. Their
      progress on chemotherapy was assessed by abdominal computerized tomography and
      laparoscopy. RESULTS: The computerized abdominal tomography scans proved
      difficult to interpret because of adhesions and matted small bowel resulting from
      the patients original colectomies. These findings made it difficult to
      differentiate postoperative changes from residual desmoid tumor. Second-look
      laparotomy in such patients was contraindicated as this may predispose to further
      desmoid production. Laparoscopy disclosed a complete response to this
      chemotherapy. Nevertheless, we had an iatrogenic small bowel perforation in one
      of these patients. Each patient showed a complete response to chemotherapy.
      CONCLUSION: Surgical resection remains the first-line treatment of intraabdominal
      desmoid tumors. However, doxorubicin/dacarbazine chemotherapy on a clinical trial
      basis may be indicated in patients whose intra-abdominal desmoid is unresectable,
      or who have failed to respond to treatment with hormones (tamoxifen, Toremifene),
      steroids (prednisone), and nonsteroidal anti-inflammatory agents (Clinoril; Merck
      & Co., Inc., West Point, PA).

PMID- 8137674
TI  - Laparoscopic sigmoid colectomy: total laparoscopic approach.
AB  - Laparoscopic surgery seems set to make a significant impact on the practice of
      colorectal surgery. However, to date, the majority of surgeons have used a
      technique of laparoscopic assistance whereby initial laparoscopic mobilization of
      the bowel is followed by extracorporeal mesenteric and bowel division and
      subsequent restoration of bowel continuity. This report describes a technique of
      totally laparoscopic left-sided colonic resection, transanal specimen delivery,
      and intracorporeal colorectal anastomosis. The technique employed is described in
      detail and the indications and controversies surrounding such an approach are
      discussed.

PMID- 8137675
TI  - Value of carcinoembryonic antigen in the management of colorectal cancer.
AB  - PURPOSE: The practical value of carcinoembryonic antigen (CEA) assay in the
      management of colorectal cancer after surgery is controversial. The value of CEA
      in the management of colorectal cancer was reviewed and discussed to justify the
      use of CEA assay in the management of colorectal cancer. METHODS: A retrospective
      study was performed on 318 patients who underwent resection by one surgeon (JYW)
      between 1981 and 1986 and who were followed for a minimum of 5 years or until
      death. RESULTS: The incidence of preoperative CEA levels > 5 ng/ml in Dukes
      Stages A, B, C, and D were 0, 32, 48, and 79 percent, respectively. Five-year
      survival rates for groups with CEA levels < or = 5 ng/ml and > 5 ng/ml were 85
      percent and 55 percent (P < 0.05), respectively, in Dukes Stage B patients and 64
      percent and 37 percent (P < 0.05) in Stage C patients. The sensitivity and
      specificity of postoperative CEA monitoring in detecting recurrent diseases were
      66 percent and 94 percent, respectively, for patients with a preoperative CEA
      value < or = 5 ng/ml and 97 percent and 88 percent for patients with a higher
      preoperative CEA value. CONCLUSION: CEA is still the best tumor marker available
      to be used as an independent prognostic factor and as a monitor for recurrence of
      disease after primary tumor resection.

PMID- 8137676
TI  - Intra-abdominal "reservoir" in patients with permanent ileostomy. Preliminary
      observations on a procedure resulting in fecal "continence" in five ileostomy
      patients. 1969.

PMID- 8137677
TI  - Grading of incontinence after surgery for anal fistulas.

PMID- 8137678
TI  - Outcome of delayed hemorrhage following surgical hemorrhoidectomy.

PMID- 8137679
TI  - Parasympathomimetics in Ogilvie's syndrome.

PMID- 8137680
TI  - Increased risk factors for coronary artery disease in Japanese subjects with
      hyperinsulinemia or glucose intolerance.
AB  - OBJECTIVE: To understand the interrelationship of coronary artery disease (CAD)
      risk factors including hyperlipidemia, hypertension, and glucose intolerance to
      prevent and better manage this disease. RESEARCH DESIGN AND METHODS: We performed
      a 100-g oral glucose tolerance test in 2,113 subjects, and we evaluated their
      plasma lipid levels, blood pressure (BP), and plasma glucose and plasma insulin
      responses. RESULTS: Multiple regression analysis demonstrated a significant
      relationship of either BP, plasma triglyceride (TG), or high-density lipoprotein
      (HDL) cholesterol levels to plasma insulin and glucose response after the glucose
      load. Plasma cholesterol levels were related only to the plasma glucose response.
      In subjects matched for age, sex, and body mass index (BMI) with hyperinsulinemia
      or normoinsulinemia, the hyperinsulinemic subjects had a significantly higher
      mean BP and plasma TG level than the normoinsulinemic subjects (128.8/82.3 vs.
      122.9/79.3 mmHg and 172.1 vs. 119.4 mg/dl), and the HDL-cholesterol level was
      significantly lower (43.9 vs. 47.8 mg/dl). Furthermore, subjects matched for age,
      sex, and BMI with glucose intolerance had a higher mean BP (128.4/81.8 vs.
      123.5/78.7 mmHg) and higher plasma TG level (154.2 vs. 123.0 mg/dl) than those
      without glucose intolerance. CONCLUSIONS: Based on these findings, subjects with
      hyperinsulinemia or glucose intolerance should be carefully managed to prevent
      CAD, because they have more numerous and more severe risk factors than subjects
      with normal plasma insulin levels or subjects without glucose intolerance.

PMID- 8137681
TI  - The predictive value of microalbuminuria in IDDM. A five-year follow-up study.
AB  - OBJECTIVE: To investigate the predictive value of microalbuminuria and the annual
      increase of albumin excretion as risk factors for diabetic nephropathy. RESEARCH
      DESIGN AND METHODS: A 5-year follow-up of patients with microalbuminuria (urinary
      albumin excretion [UAE] = 30-299 mg/24 h) and matched patients with
      normoalbuminuria (UAE < 30 mg/24 h). The initial classification was based on one
      single 24-h urine collection. The annual increase in UAE was calculated by linear
      regression analysis of log-transformed UAE on time. This study was conducted at
      the outpatient clinic of the Steno Diabetes Center. The study subjects included
      118 insulin-dependent diabetes mellitus (IDDM) patients between 18 and 50 years
      of age with microalbuminuria and 112 matched control patients with normal UAE
      with an age at diabetes onset of < 31 years. The main outcome measures were UAE,
      annual change in UAE rate (percentage per year), and the prevalence of
      retinopathy. RESULTS: After 5 years, 39 (33%, 24-42 CI [95% confidence interval])
      patients with microalbuminuria had normoalbuminuria, 57 (48%, 38-57 CI) still had
      microalbuminuria, and 22 (19%, 12-27 CI) had developed diabetic nephropathy.
      Among the 112 patients with normoalbuminuria in 1985, 9 (8%, 4-15 CI) had
      developed microalbuminuria, and 2 (2%, 0-6 CI) had developed diabetic
      nephropathy. Of the 79 patients with persistent albuminuria, only 36 (46%, 34-57
      CI) were progressors with a rate of progression of > 5%/year. Progressors had
      significantly higher HbAlc, higher mean blood pressure, and a higher incidence of
      proliferative retinopathy compared with nonprogressors. Multiple regression
      analysis only identified mean HbAlc as an independent predictor of the rate of
      progression. Smoking was significantly more prevalent in patients with persistent
      albuminuria. CONCLUSIONS: Microalbuminuria is a predictor of progression to
      diabetic nephropathy; however, not as strong as suggested previously. Calculation
      of the annual increase in UAE seems to be a more specific method of identifying
      patients who will develop diabetic nephropathy.

PMID- 8137682
TI  - Smoking is associated with progression of diabetic nephropathy.
AB  - OBJECTIVE: To investigate the association between cigarette smoking and the
      progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: A prospective,
      follow-up study over one year was conducted in a sequential sample of 34 smokers,
      35 nonsmokers, and 24 ex-smokers with type I diabetes, hypertension, and diabetic
      nephropathy. Progression of renal disease was defined according to the stage of
      nephropathy as an increase in proteinuria or serum creatinine or a decrease in
      the glomerular filtration rate. RESULTS: Progression of nephropathy was less
      common in nonsmokers (11%) than in smokers (53%) and patients who had quit
      smoking (33%), P < 0.001. In a stepwise logistic regression analysis, cigarette
      pack years, 24-h sodium excretion, and GHb were independent predictive factors
      for the progression of diabetic nephropathy. Because blood pressure (BP) was well
      controlled in these patients and most values were within a normotensive range,
      neither standing, sitting, nor supine BP values were associated with progression
      of nephropathy. CONCLUSIONS: Cigarette smoking represents an important factor
      associated with progression of nephropathy in treated hypertensive type I
      diabetic patients.

PMID- 8137683
TI  - Ethnic differences in human leukocyte antigen markers of susceptibility to IDDM.
AB  - OBJECTIVE: To determine whether genetic differences explain the lower risk of
      developing insulin-dependent diabetes mellitus (IDDM) for Hispanic versus non
      Hispanic white children in Colorado. RESEARCH DESIGN AND METHODS: Hispanic (n =
      62) and non-Hispanic white (n = 82) subjects with IDDM identified from the
      Colorado IDDM Registry and healthy, nondiabetic control subjects were recruited.
      Human leukocyte antigen (HLA) serologic typing and sequence-specific
      oligonucleotide typing of DQA1 and DQB1 alleles were performed. RESULTS: HLA and
      allele associations with IDDM were similar in both ethnic groups. HLA-DR3 and HLA
      DR4 were more common in IDDM subjects in both ethnic groups. Subjects with DQBl
      alleles encoding aspartic acid (Asp) in position 57 were less likely to have
      IDDM, irrespective of ethnic background. HLA-DR3 was less common among Hispanic
      subjects than non-Hispanic white control subjects (4.4 vs. 17.5%, Hispanics vs.
      non-Hispanic whites, P = 0.04). CONCLUSIONS: These data suggest that the lower
      prevalence of HLA-DR3 in the Hispanic population, a pattern consistent with the
      presence of Amerindian admixture, may explain the lower rate of IDDM in the
      Hispanic population.

PMID- 8137685
TI  - Slow elimination of glyburide in NIDDM subjects.
AB  - OBJECTIVE: To determine the terminal elimination half-life of glyburide in non
      insulin-dependent diabetes mellitus (NIDDM) subjects after cessation of long-term
      treatment. RESEARCH DESIGN AND METHODS: Ten NIDDM patients (5 of each sex, 36-72
      years old, without hepatic or renal disease) taking a median glyburide dose of 14
      mg/day, who were to start insulin therapy because of sulfonylurea failure, were
      studied. Serum glyburide concentrations, measured by a newly developed selective
      and sensitive liquid chromatographic method, were followed from 10 to 48 h after
      the last glyburide dose. RESULTS: Serum glyburide levels declined in three
      different phases, with a terminal gamma-phase between 18 and 48 h having a mean
      +/- SD half-life of 15.0 +/- 6.7 h. Two patients had half-lives over 20 h. The
      half-life values did not correlate with fasting blood glucose, age, body weight,
      body mass index, or creatinine levels. The latter agrees with the assumption that
      glyburide is completely eliminated by metabolic transformation. Although longer
      than previously observed, the current half-life values are in accordance with
      clinical experience that glyburide is a long-acting sulfonylurea. CONCLUSIONS:
      The elimination of glyburide in NIDDM subjects is slower than previously
      reported. The long half-life adds support to the use of a once-daily dosage of
      glyburide. It also justifies increased caution when using this sulfonylurea.

PMID- 8137686
TI  - Use of runs test to assess cardiovascular autonomic function in diabetic
      subjects.
AB  - OBJECTIVE: We suggest a simple, noninvasive method to assess the autonomic
      function in diabetic subjects. The method requires only a monitoring of heart
      rate (HR) with subjects in the sitting position. RESEARCH DESIGN AND METHODS:
      Sixty diabetic subjects, 44 men and 16 women, between 20-80 years of age, were
      recruited, chronologically, for this study. Subjects treated for high blood
      pressure were not included. Their autonomic function was assessed by the total
      score of five classical cardiovascular function tests. In the same subjects and
      in 44 healthy subjects, blood pressure and HR were determined from beat to beat
      by the Finapres system with subjects in the sitting position. We examined the
      randomness of the HR changes by calculating the zeta statistic of the runs test
      on 1,000 successive HR readings (the zeta value is low if the HR changes are
      random). When the HR changes are random, we consider that the autonomic control
      of HR is impaired. RESULTS: The zeta values of HR changes were significantly
      lower in diabetic subjects compared with normal subjects (2.98 +/- 0.97 vs. 3.54
      +/- 0.97, P < 0.004). In diabetic subjects, the zeta value was closely correlated
      to the total score of disautonomy (r = -0.66, P < 0.0001, after correction for
      age effect) and to the office systolic blood pressure (r = -0.43, P < 0.001).
      CONCLUSIONS: The zeta value of HR changes might be a marker of the autonomic
      function in diabetic subjects.

PMID- 8137684
TI  - Linear loss of insulin secretory capacity during the last six months preceding
      IDDM. No effect of antiedematous therapy with ketotifen.
AB  - OBJECTIVE: To investigate the effect of an antiedematous therapy with the
      histamine antagonist ketotifen on beta-cell function in late prediabetes.
      RESEARCH DESIGN AND METHODS: In a randomized double-blind placebo-controlled
      study, ketotifen was administered for 3 months to 9 islet cell antibody positive
      (ICA+) prediabetic patients with a first-phase insulin response (FPIR) below the
      2.5th percentile to preserve residual beta-cell function. Patients were followed
      by intravenous glucose tolerance tests (IVGTTs) every 4-6 weeks for determination
      of FPIR, HbA1, ICAs, and insulin autoantibodies. In 5 patients, the immune
      activation state was followed by determination of serum levels of tumor necrosis
      factor-alpha (TNF-alpha), beta 2-microglobulin, and C-reactive protein (CRP).
      RESULTS: Seven of nine patients developed diabetes within one year of follow-up.
      Irrespective of treatment with ketotifen, a slow and linear decline (P < 0.05) of
      1 + 3-min insulin values was observed in sequential IVGTTs in those 7 patients
      who developed insulin-dependent diabetes mellitus (IDDM) during follow-up. The 2
      other patients showed wide fluctuations of the insulin response with a threefold
      increase of initial insulin levels. HbA1 did not correlate with FPIR. Fasting
      blood glucose increased significantly during the study (P < 0.05). Individual
      levels of serum TNF-alpha, CRP, and beta 2-microglobulin did not change during
      the study. CONCLUSIONS: The study could not demonstrate preservation of beta-cell
      function by ketotifen in the late stage before manifestation of clinical
      diabetes. Manifestation is preceded in the last 6 months by a steady loss of the
      FPIR without rapid deterioration immediately before diagnosis and without signs
      of increased immune activity.

PMID- 8137687
TI  - Detection of early sympathetic cardiovascular neuropathy by squatting test in
      NIDDM.
AB  - OBJECTIVE: To determine the role of the squatting test in the detection of early
      sympathetic neuropathy in patients with non-insulin-dependent diabetes mellitus
      (NIDDM). RESEARCH DESIGN AND METHODS: Three groups of nonsmoking, nonobese
      subjects were studied: 10 healthy subjects, 10 NIDDM patients without autonomic
      neuropathy (AN), and 10 NIDDM patients with AN defined by the presence of a
      pathological deep-breathing value. All subjects were given three postural tests:
      lying-to-standing, sitting-to-standing, and squatting test. Heart rate (HR) and
      finger arterial pressure were recorded with a noninvasive technique. RESULTS:
      Blood pressure (BP) fall (expressed as decremental area) was not significantly
      different among the groups at standing up after sitting or lying. By contrast, a
      significantly greater BP drop occurred in NIDDM patients with AN (1,123 +/- 245
      mm2) compared with NIDDM patients without AN (460 +/- 232 mm2) or normal subjects
      (429 +/- 138 mm2, P < 0.001). The HR increase after all the orthostatic maneuvers
      was smaller in diabetic patients with AN (P < 0.01) compared with that recorded
      in other groups. Significant correlations were observed between BP fall after
      squatting and either the expiration:inspiration ratio at deep breathing (r = 
      0.77, P < 0.001) or the duration of diabetes (r = 0.76, P < 0.001). CONCLUSIONS:
      The intrinsic orthostatic load of the squatting test, which is greater than
      conventional postural maneuvers, makes the squatting test an easy and useful test
      to detect early orthostatic dysregulation in NIDDM.

PMID- 8137688
TI  - A mathematical model for the determination of total area under glucose tolerance
      and other metabolic curves.
AB  - OBJECTIVE: To develop a mathematical model for the determination of total areas
      under curves from various metabolic studies. RESEARCH DESIGN AND METHODS: In
      Tai's Model, the total area under a curve is computed by dividing the area under
      the curve between two designated values on the X-axis (abscissas) into small
      segments (rectangles and triangles) whose areas can be accurately calculated from
      their respective geometrical formulas. The total sum of these individual areas
      thus represents the total area under the curve. Validity of the model is
      established by comparing total areas obtained from this model to these same areas
      obtained from graphic method (less than +/- 0.4%). Other formulas widely applied
      by researchers under- or overestimated total area under a metabolic curve by a
      great margin. RESULTS: Tai's model proves to be able to 1) determine total area
      under a curve with precision; 2) calculate area with varied shapes that may or
      may not intercept on one or both X/Y axes; 3) estimate total area under a curve
      plotted against varied time intervals (abscissas), whereas other formulas only
      allow the same time interval; and 4) compare total areas of metabolic curves
      produced by different studies. CONCLUSIONS: The Tai model allows flexibility in
      experimental conditions, which means, in the case of the glucose-response curve,
      samples can be taken with differing time intervals and total area under the curve
      can still be determined with precision.

PMID- 8137689
TI  - The potential role of diabetes guidelines in the reduction of medical injury and
      malpractice claims involving diabetes.

PMID- 8137690
TI  - IDDM and celiac disease.

PMID- 8137691
TI  - Comments on "The response of GHb to stepwise plasma glucose change over time in
      diabetic patients".

PMID- 8137692
TI  - Plasma endothelin in diabetic autonomic neuropathy.

PMID- 8137693
TI  - Is noncompliance a dirty word?

PMID- 8137694
TI  - Adherence behaviors in research protocols: comparison of two interventions.
AB  - The effectiveness of an enhanced preparation intervention was compared with the
      standard preparation intervention for accuracy in overnight urine specimen
      collections. The sample consisted of 179 individuals with type I insulin
      dependent diabetes mellitus (IDDM). Subjects were assigned randomly to an
      enhanced or standard preparation group. The enhanced preparation included written
      instructions, a reminder to post instructions in the bathroom, a toilet seat
      cover with a reminder to save urine, and a nurse-initiated telephone call to
      review the instructions. The standard preparation included written instructions
      and a telephone number to call with any questions. For subjects without previous
      collection experience, significantly fewer inaccurate collections were reported
      in the enhanced preparation group than in the standard group (chi 2 = 4.61, P <
      .05). There were no differences in collection accuracy between enhanced and
      standard groups for subjects with collection experience (chi 2 = .4598, P > .05).

PMID- 8137695
TI  - The relationship among six psychosocial domains, age, health care adherence, and
      metabolic control in adolescents with IDDM.
AB  - This pilot study examined the relationship among six psychosocial factors, age,
      health care compliance, and metabolic control in adolescents with IDDM. Four
      objectives were identified: 1) to determine whether specific compliance areas
      predict metabolic control; 2) to determine whether specific psychosocial factors
      predict metabolic control; 3) to determine whether compliance and psychosocial
      issues change with age; and 4) to determine whether the parent or the youth is
      the more accurate predictor of metabolic control. Twenty-one adolescents age 13
      through 18 years participated in this study. Dietary compliance was found to be
      the best predictor of metabolic control. Parents more accurately predicted
      metabolic control for youths younger than 16 years old, while the reverse was
      true for older youths. A negative relationship was identified among strong self
      concept, high knowledge of IDDM, parental support, and poor metabolic control.
      Several possible explanations are discussed, including power struggles, coping
      difficulties, and fear of peer reactions.

PMID- 8137696
TI  - Evaluation and comparison of the nutrition care process for persons with diabetes
      among inpatient and outpatient dietitians.
AB  - The purpose of this study was to compare the problem-solving skills used by
      dietitians when planning care for inpatient and outpatient persons with type II
      diabetes. Telephone interviews were conducted with 44 inpatient dietitians and 45
      outpatient dietitians. Inpatient dietitians used more information from the
      medical record to make clinical judgments than outpatient dietitians. Inpatient
      dietitians reported condensing their assessment more frequently due to time
      pressure than outpatient dietitians. Inpatient dietitians were more likely to
      identify nutrition-related problems via information from the medical record while
      outpatient dietitians reported using diet history information. Outpatient
      dietitians more frequently identified specific behavioral goals whereas inpatient
      dietitians recommended general goals. The increased availability of objective,
      detailed information necessary for a thorough nutritional assessment is an
      advantage of inpatient care planning. However, outpatient diabetes education may
      be a preferred setting because of more time available for education and better
      learning effectiveness.

PMID- 8137697
TI  - Ingredients that replace fat: their role in today's foods and challenges in
      educating people with diabetes.
AB  - This article reviews the three categories of fat replacers and characteristics of
      the individual products. Most importantly, this update provides strategies for
      staying abreast of current and future foods, and stimulates considerations for
      diabetes educators when advising clients about fat-modified foods. Creative
      techniques and tools also are presented for educating clients about these foods.

PMID- 8137698
TI  - Lipid-lowering diets: putting guidelines into practice.
AB  - The incidence of cardiovascular disease is four to five times greater in people
      with diabetes than in people without diabetes. Lipid disorders, along with
      elevated blood pressure, cigarette smoking, and abdominal obesity, are major risk
      factors for people with diabetes. All adults with diabetes should be screened for
      blood lipid levels including triglycerides, cholesterol, and high-density
      lipoprotein (HDL) cholesterol. The low-density lipoprotein (LDL) cholesterol
      should be measured more routinely in people with diabetes than suggested in the
      National Cholesterol Education Project (NCEP) guidelines. No single diet is best
      for persons with diabetes. Sometimes a lower fat, higher carbohydrate diet is
      more acceptable, and other times a lower carbohydrate, higher monounsaturated
      fatty acid (MUFA) diet is preferred. The decision regarding the level of fat in
      the diet is based both on patient preference as well as serial measurements of
      metabolic control. Changing eating habits regarding lipids is a gradual process
      and can best be accomplished when introduced in a staged approach.

PMID- 8137699
TI  - Diabetic complications from the patient's viewpoint.

PMID- 8137700
TI  - Pancreatic cancer and diabetes.
AB  - Whether having diabetes predisposes an individual to developing pancreatic cancer
      continues to be studied. At present, the greater challenge for diabetes educators
      is to help those individuals who have had surgical resection for pancreatic
      cancer and now have resultant IGT or frank diabetes to manage their condition to
      the best of their ability and make their quality of life the best it can be,
      given the circumstances.

PMID- 8137701
TI  - Evaluation of an activated patient diabetes education newsletter.
AB  - This study evaluated a monthly, activated patient newsletter sent to over 7000
      patients in Michigan with diabetes. The newsletter provided concise and action
      oriented information about diabetes care. Patients who had signed up to receive
      the newsletter during the first 4 months of the project (1863) were surveyed to
      determine how many patients found the newsletter helpful; 80% (1498) of the
      patients replied. Patients who found the newsletter most helpful were older; had
      lower incomes, and reported more complications, less understanding of diabetes,
      and being in poorer overall health. They also were more likely to have non
      insulin-dependent diabetes mellitus (NIDDM) than insulin-dependent diabetes
      mellitus (IDDM). We concluded that the activated patient newsletter is a useful
      public health/patient education intervention for persons with diabetes. Such a
      newsletter should be part of a coordinated system of ongoing patient care,
      education, screening, and social and psychological support.

PMID- 8137702
TI  - Dissemination of a continuing education program in diabetes to health care
      professionals.
AB  - A goal of the Diabetes Research and Training Centers (DRTCs) is to translate
      advances in diabetes research into improved patient care by providing innovative,
      state-of-the-art training for health care professionals. This paper is a report
      on a collaborative DRTC-AADE training project. A 2-day diabetes program developed
      by the Chicago DRTC was packaged as a Workshop Instructor's Guide with
      accompanying slides and materials. AADE faculty observed the workshop presented
      by DRTC faculty and subsequently presented the workshop themselves. The
      evaluation design involved comparing a workshop presented by the DRTC faculty
      with a workshop presented by faculty from AADE. Three components were included in
      the evaluation: the participants' evaluation, a commitment-to-change evaluation,
      and the faculty observations. When comparing workshops, few differences were
      observed in participants' or faculty observers' evaluations. Moreover,
      participants at both workshops were equally successful at meeting goals related
      to improving their diabetes education practice behaviors. Dissemination of the
      program has been expanded and the workshop has become part of AADE's national
      continuing education efforts.

PMID- 8137703
TI  - Visual interpretation of blood glucose test strips.
AB  - Patients with type II, non-insulin-dependent diabetes mellitus (NIDDM) typically
      are middle-aged or older and often have diabetic retinopathy. The visual acuity
      of these patients also is likely to be reduced beyond what is normally associated
      with age. Because Medicaid does not reimburse NIDDM patients for a blood glucose
      meter unless they are insulin-dependent, many low-income diabetes patients are
      required to monitor their blood glucose levels by visually comparing the color
      spot on the blood glucose test strip with a series of standard color blocks.
      Unless patients can accurately assess their blood glucose levels by visual
      interpretation of the test strips, they will have difficulty maintaining adequate
      glycemic control. In this study, 60 nondiabetic adults, ages 20 to 78 years, were
      unable to adequately assess blood glucose levels visually, even under optimal
      lighting conditions. Younger adults made the same number of errors as older
      adults, and poor visual acuity and high blood glucose values were associated with
      more errors. These findings suggest that patients with poor visual acuity or
      those who read their blood glucose strips in less-than-adequate lighting will
      make even more errors than our test subjects.

PMID- 8137704
TI  - Traditional vs anchored instruction for diabetes-related nutritional knowledge,
      skills, and behavior.
AB  - This paper describes a nutrition education experiment in which traditional direct
      instruction was compared with a problem-solving method called anchored
      instruction (AI). Participants were 69 children ages 9 to 15 years, with insulin
      dependent diabetes mellitus (IDDM), who attended a diabetes camp. Following
      pretesting, campers were assigned to AI or direct instruction control classes.
      Posttests involved evaluating diabetes knowledge, personal meal plan knowledge,
      ability to choose an appropriate meal from a buffet line, and ability to pack
      appropriate meals for an overnight campout. AI and direct instruction both
      produced significant knowledge gains in this study. However, because the scores
      for the two groups did not differ, this study was unsuccessful in replicating
      results of other studies or extending the findings to selected measures of actual
      behavior.

PMID- 8137705
TI  - The impact of a diabetes nurse educator on nurses' knowledge of diabetes and
      nursing interventions in a home care setting.
AB  - The purpose of this study was to compare nurses' knowledge of diabetes and
      nursing interventions in a home health care agency (HHCA) that employed a
      diabetes nurse educator (DNE) and an agency that did not employ a DNE. Nurse
      knowledge of diabetes mellitus was measured using the Diabetes: Basic Knowledge
      Test (DBKT). Nursing care interventions for patients with diabetes were measured
      using a researcher-developed tool, the Nursing Care Intervention Tool (NCIT). The
      data analysis showed that the nurses in the agency with the diabetes nurse
      educator were significantly more knowledgeable about diabetes. The data also
      showed that the nurses in the HHCA with a diabetes nurse educator provided a
      significantly higher standard of patient care than the nurses in the agency
      without a diabetes nurse educator.

PMID- 8137706
TI  - The process of establishing and maintaining nursing staff competence in educating
      patients being placed on insulin pump therapy.

PMID- 8137707
TI  - Exploring the psychosocial aspects of diabetes: the yellow ball.

PMID- 8137708
TI  - Should you be eating that?

PMID- 8137709
TI  - DCCT: model of partnership.

PMID- 8137710
TI  - Good diabetic control does prevent chronic complications--an idea whose time has
      come.

PMID- 8137711
TI  - Biguanides may produce hypoglycemic action in isolated rat hepatocytes through
      their effects on L-alanine transport.
AB  - We investigated the mechanisms of the effects of the biguanides metformin and
      buformin on hepatic gluconeogenesis in hepatocytes isolated from normal rats.
      Both 10 nM glucagon and 50 microM dibutyryl cAMP increased [3H]alanine uptake in
      isolated hepatocytes of normal rats by about 150% and 55%, respectively, compared
      with the effect of 5 mM alanine alone. Metformin (3 mM) reduced glucagon
      stimulated [3H]alanine uptake to the level seen with alanine alone; buformin (3
      mM) inhibited glucagon-stimulated [3H]alanine uptake by about 69%. The effects of
      biguanides on dibutyryl cAMP-stimulated [3H]alanine uptake were similar, but of
      smaller magnitude compared with those observed in the presence of glucagon.
      Ouabain (3 mM) had a stronger inhibitory effect on [3H]alanine uptake than the
      biguanides. However, 3 mM tolbutamide failed to suppress [3H]alanine uptake in
      the presence or absence of glucagon or dibutyryl cAMP. Our results suggest that
      the inhibition of alanine uptake, related to a reduction in the Na+/L-alanine
      transport system, is a possible mechanism of biguanide-related inhibition of
      hepatic gluconeogenesis.

PMID- 8137712
TI  - Nicotinamide, a poly (ADP-ribose) synthetase inhibitor, ameliorates B-cell
      function in partially depancreatized rats.
AB  - We studied the effect of nicotinamide, a poly (ADP-ribose) synthetase inhibitor,
      on B-cell functions in 7-week-old male Wistar rats after 90% pancreatectomy (Px).
      Nicotinamide (0.5 g/kg body wt.) was injected once a day i.p. from 1 week before
      the surgery, and the injection was continued for 12 weeks after Px. Plasma
      glucose levels were significantly lower in Px rats treated with nicotinamide (NA
      rats) than in Px rats without treatment. In in vitro experiments with perfusion
      of the isolated pancreas, insulin secretion induced by 16.7 mM glucose was
      blunted in Px rats whereas insulin secretion induced by 19 mM arginine was
      increased. Nicotinamide treatment restored glucose-induced insulin secretion to
      normal and partly suppressed the hyperresponse of insulin to arginine. In
      addition, nicotinamide partially restored the priming effect induced by 28 mM
      glucose. The insulin content of the perfused pancreas was slightly but
      significantly greater in NA rats than in Px rats. Histological examination
      revealed fibrotic degeneration and degranulation in the islets of Px rats,
      whereas the normal structure was retained in most islets of NA rats. These
      results suggest that nicotinamide ameliorates islet function in partially
      depancreatized rats.

PMID- 8137713
TI  - Voluntary exercise improves glycemia in non-obese diabetic (NOD) mice.
AB  - The non-obese diabetic (NOD) mouse was used to investigate the effects of
      voluntary wheel running exercise on blood glucose levels, glycosylated
      hemoglobin, and longevity in Type 1 diabetes mellitus. In Experiment 1, diabetic
      and normoglycemic mice exercised 5 h/day, 5 days/week for 3 weeks matched with
      non-exercising controls. In diabetic animals a positive correlation was found
      between blood glucose and the number of revolutions performed (P < or = 0.02).
      Exercise also significantly lowered blood glucose between baseline and post
      exercise in both diabetic and normoglycemic animals. In Experiment 2, mice
      exercised 2 h/day, 5 days/week. For the diabetic animals, glycosylated hemoglobin
      was lower than that of matched non-exercising diabetic animals at week 3 (11.1 +/
      0.6% vs. 15.0 +/- 1.6%, P < 0.001). Diabetic runners were able to train and
      significantly increased running in the first 4 weeks (P < 0.05). At the end of 9
      weeks all 5 diabetic runners were alive, compared with 3 of 5 non-running
      diabetic animals. We conclude: (i) the NOD mouse is a useful model for the study
      of exercise in Type 1 diabetes, (ii) running exercise is associated with a drop
      in blood glucose, (iii) the amount of voluntary exercise performed correlates
      with blood glucose in diabetic animals, and (iv) diabetic mice will increase
      running distance in the first few weeks after diagnosis.

PMID- 8137714
TI  - Effects of glimepiride on in vivo insulin action in normal and diabetic rats.
AB  - To evaluate the effects of glimepiride on insulin action in peripheral tissues,
      we investigated insulin-induced glucose uptake in normal and diabetic rats using
      the euglycemic clamp procedure (insulin infusion rates: 6 and 30 mU/kg/min).
      Normal rats: After oral administration of glimepiride (0.1 mg/kg/day; NG) or
      saline (NC) for 2 weeks, euglycemic clamp procedures were performed. During
      submaximal hyperinsulinemia (620 +/- 35 pmol/l, mean +/- S.E.M.), metabolic
      clearance rates of glucose (MCR) in NG were significantly higher than in NC (25.1
      +/- 2.1 vs. 18.3 +/- 1.2 ml/kg/min, P < 0.05). During maximal hyperinsulinemia
      (5235 +/- 270 pmol/l), MCRs in NG were higher than in NC, but there was no
      statistical significance (43.3 +/- 2.8 and 38.9 +/- 2.8). Diabetic rats:
      streptozotocin-induced diabetic rats were divided into four groups, GI
      (glimepiride treatment, 0.1 mg/kg/day p.o., with insulin, 5 U/day s.c.), SI
      (insulin alone), SG (glimepiride alone), and SC (saline). MCRs in the four groups
      were similar during 6 mU/kg/min clamps. During 30 mU/kg/min clamps, MCRs in GI
      were significantly higher than those in SC, SG or SI (23.4 +/- 2.8 vs. 12.2 +/-
      1.9 and 8.9 +/- 0.8, P < 0.01, and vs. 17.4 +/- 1.5, P < 0.05). Although MCRs in
      SI tended to be higher than in SC, there was no significant statistical
      difference between these two groups. These results suggest that glimepiride
      enhances insulin action in peripheral tissues, and that glimepiride treatment
      with insulin improves the insulin resistance observed in streptozotocin-induced
      diabetic rats.

PMID- 8137715
TI  - Incidence of altered glucose tolerance in liver cirrhosis.
AB  - Even though the association between liver cirrhosis and glucose tolerance
      alterations has been well documented, no data are available on the incidence of
      this association. In this paper we firstly report the results of a 4-year
      prospective longitudinal study performed on well-compensated cirrhotic patients
      with a normal glucose tolerance, in order to evaluate the incidence of glucose
      tolerance alterations with respect to liver efficiency during the time. The
      incidence of a diabetic response to a standard OGTT was 4.4% after a 1-year and
      21.2% after a 4-year follow-up in stable cirrhotics. These figures are
      significantly higher than in the general population of our country. This large
      incidence was even significantly higher in cirrhotics with worsening liver
      efficiency at the end of the study (35.3%, P < 0.0001). Sex, family history of
      diabetes, alcoholic aetiology of the cirrhosis, and increment of portal
      hypertension do not seem to have any significant influence on the frequency of
      altered glucose tolerance. Therefore, we propose that liver cirrhosis and its
      worsening play a primary role as diabetogenic risk factors.

PMID- 8137716
TI  - Glomerular clearance and tubular reabsorption of IgG1 and IgG4 in
      microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM).
AB  - The alteration in glomerular clearance (GC) and tubular reabsorption (TR) of IgG
      subclass (IgG1 and IgG4, same molecular weight, but differing charge) was
      investigated in 14 microalbuminuric patients with non-insulin-dependent diabetes
      mellitus (NIDDM) by inhibiting TR of proteins by L-arginine infusion; 16 healthy
      volunteers served as controls. In healthy volunteers, GC was in the following
      order: IgG1 > IgG4 > or = albumin. In microalbuminuric patients, as compared with
      control, GC of albumin was increased significantly; the GC of IgG4 was twice that
      of control, while GC of IgG1 decreased reciprocally. The TR in controls was in
      the following order; albumin > IgG1 > IgG4. In microalbuminuric patients, TR of
      albumin was significantly reduced, TR of IgG1 was moderately reduced and that of
      IgG4 remained at same level as controls. These observations suggest that the
      enhancement of GC of albumin in NIDDM was produced by an impaired glomerular
      anionic charge barrier, while the mechanism for the reduction in TR of albumin
      was attributable to other undefined mechanisms.

PMID- 8137717
TI  - Effects of cilostazol, a phosphodiesterase inhibitor, on urinary excretion of
      albumin and prostaglandins in non-insulin-dependent diabetic patients.
AB  - Microalbuminuria is characteristic in diabetic nephropathy and is thought to be
      influenced by renal hemodynamics, especially by the metabolism of prostaglandins
      (PGs) in glomruli. To reduce urinary albumin excretion in patients with non
      insulin-dependent diabetes mellitus (NIDDM), we administered 100 mg of
      cilostazol, a phosphodiesterase inhibitor, daily for 3 months. The urinary
      albumin index (UAI: microgram albumin/mg creatinine) decreased significantly
      after 3 months of administering cilostazol. Urinary excretions of thromboxane B2
      (TXB2), a stable metabolite of thromboxane A2, decreased significantly after
      treatment. However, it had no effects on urinary excretions of PGE2 and 6-keto
      PGF1 alpha (6KF), a stable metabolite of prostacyclin. The ratio 6KF/TXB2 has
      been known to reflect the renal metabolism of PGs. In this study, urinary
      6KF/TXB2 ratio increased significantly in parallel with a significant reduction
      of UAI. Cilostazol had no adverse effects on the control of blood glucose and
      lipids. In conclusion, cilostazol has a beneficial effect on UAI in patients with
      NIDDM by reducing renal production of TXB2., which increases 6KF/TXB2 ratio.

PMID- 8137718
TI  - High viscosity hydroxypropylmethylcellulose reduces postprandial blood glucose
      concentrations in NIDDM patients.
AB  - The ability of high viscosity hydroxypropylmethylcellulose (HPMC) to reduce
      postprandial glucose concentrations was assessed in patients with non-insulin
      dependent diabetes (NIDDM) and healthy volunteers. The study design consisted of
      a two-way crossover, single-dose administration of 10 g prehydrated high
      viscosity HPMC, or placebo, with a standard carbohydrate-rich meal. In patients
      with NIDDM, HPMC reduced blood glucose concentrations at the 60-, 75-, 90-, 120-
      and 150-min sampling intervals, with an average reduction in the maximum
      postprandial blood glucose concentration, Cmax, of 24% (P < 0.05). The time at
      which the maximum concentration was reached, Tmax, remained unchanged. The area
      under the blood concentration versus time plot, AUC0-6h, was reduced by an
      average of 15% (P < 0.05). The blood concentration profile of insulin followed
      that of glucose. Concentrations were significantly lower than in the placebo
      phase only at the 120-min sampling time, while pharmacokinetic parameters (Cmax,
      Tmax and AUC0-6h) were unchanged. These results suggest that alterations in the
      blood glucose profile are mediated by luminal events rather than by changes in
      hormonal response. In contrast to the NIDDM patients, neither the pharmacokinetic
      parameters nor the blood glucose concentrations at specific sampling times were
      significantly affected by the co-administration of HPMC in healthy volunteers.
      Overall, the results of this study suggest that HPMC may be a useful adjunct in
      the management of NIDDM.

PMID- 8137719
TI  - Comparison of anti-human insulin antibodies detection by commercial enzyme-linked
      immunosorbent assay kit, displacement enzyme-linked immunosorbent assay and
      radioimmunoassay, in Thai diabetic patients.
AB  - Antibodies specific to human insulin, in sera of Thai diabetic patients and
      normal healthy individuals, were detected by a commercial enzyme-linked
      immunosorbent assay (ELISA) kit, displacement ELISA and radioimmunoassay (RIA).
      Among 36 insulin-treated patients, the antibodies were detected in 22, 23 and 20
      individuals, by RIA, commercial ELISA kit and displacement ELISA, respectively.
      Among those who had never previously received insulin therapy, RIA showed
      positive results in 5/11 patients with insulin-dependent diabetes mellitus (IDDM)
      and 1/2 patients with fibrocalculous pancreatic diabetes (FCPD); but were
      negative in all 26 patients with non-insulin-dependent diabetes mellitus (NIDDM)
      and 30 normal healthy individuals. The commercial ELISA kit could detect such
      insulin autoantibodies (IAA) in 4/11 IDDM, 3/26 NIDDM, 2/2 FCPD patients and 4/30
      normal controls; while the displacement ELISA showed positive IAA detection in
      5/11 IDDM, 2/26 NIDDM, 2/2 FCPD and 2/30 normal controls. By using RIA as the
      'gold standard', the commercial ELISA kit had 92.86% sensitivity, 87.01%
      specificity, 88.57% accuracy, 72.22% positive predictive value and 97.10%
      negative predictive value; while these indices for the displacement ELISA were
      85.71%, 90.01%, 89.52%, 77.42% and 94.59%, respectively.

PMID- 8137720
TI  - The vitamin D endocrine system: identification of another piece of the puzzle.

PMID- 8137721
TI  - 1,25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors,
      gene expression, and insulin secretion.
AB  - Previous studies have indicated that the pancreas has receptors specific for 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3] and that 1,25-(OH)2D3 increases insulin
      secretion in vitamin D-deficient rats. In this study we report that in vitamin D
      replete, but calcium-deficient, rats in which 1,25-(OH)2D3 levels are elevated,
      insulin secretion is not altered. In addition, in in vitro studies 1,25-(OH)2D3
      at concentrations of 10(-10)-10(-7) M was consistently found to inhibit insulin
      secretion from islets of vitamin D-replete rats or from the rat insulinoma beta
      cell line RIN 1046-38. The RIN cell line was found to contain both vitamin D
      receptors and calbindin-D28k (CaBP-D28k) protein and mRNA. In RIN cells,
      treatment with sodium butyrate (2 mM for 3 days) induces a more islet phenotype,
      as indicated by increased insulin content and secretion and increased insulin
      gene expression. 1,25-(OH)2D3 treatment (50-100 nM for 48 or 72 h) had no effect
      on the enhanced levels of insulin secreted in the presence of butyrate. However,
      2 mM sodium butyrate induced CaBP-D28k protein (4-fold; control, 0.8 +/- 0.2;
      sodium butyrate, 3.5 +/- 0.1 microgram/mg protein) and mRNA (3-fold) in the RIN
      cell line, in accord with the induction by butyrate of insulin content and
      secretion and beta-cell differentiation, suggesting a possible role for CaBP-D28k
      in these processes. Although 1,25-(OH)2D3, unlike butyrate, did not enhance
      insulin secretion, both 1,25-(OH)2D3 (100 nM) and butyrate (2 mM) inhibited RIN
      cell growth (to 69% and 28% of the control, respectively), and butyrate and 1,25
      (OH)2D3 in combination led to a further inhibition of cell growth (to 13% of the
      control). In response to 1,25-(OH)2D3 (10 nM for 72 h), vitamin D receptors were
      up-regulated 313% in RIN cells [control, 37 +/- 2; 1,25-(OH)2D3 treated, 115 +/-
      5 fmol/mg protein]. In conclusion, 1) contrary to previous studies in the vitamin
      D-deficient rat, our findings indicate that 1,25-(OH)2D3 action does not
      necessarily result in enhanced insulin secretion; 2) inhibition of cell growth
      and up-regulation of vitamin D receptors by 1,25-(OH)2D3 suggest that parameters
      in addition to insulin secretion can be affected by 1,25-(OH)2D3 in the beta
      cell; 3) the RIN beta-cell line provides a novel in vitro system for studying the
      effect of the vitamin D endocrine system on pancreatic islet physiology.

PMID- 8137722
TI  - Male Fischer 344/N rats show a progressive central impairment of the hypothalamic
      pituitary-adrenal axis with advancing age.
AB  - We investigated the effects of aging on the regulation of hypothalamic-pituitary
      adrenal function and hippocampal steroid receptors in a series of in vivo and in
      vitro studies conducted in healthy intact 2-, 8-, 18-, and 24-month-old male
      Fischer 344/N rats. Basal plasma ACTH levels were similar among age groups, and
      basal plasma corticosterone levels showed a significant aging-associated decline.
      Two i.v. doses (2 and 20 micrograms/kg BW) of rat CRF elicited significantly
      greater and delayed ACTH and greater corticosterone responses in older rats,
      consistent with the pattern encountered in hypothalamic CRF deficiency. In
      contrast, the i.v. injection of a muscarinic agonist, arecoline, elicited similar
      ACTH and corticosterone responses in all age groups. An i.v. injection of ACTH-(1
      24) evoked lower corticosterone responses in the older (18- and 24-month-old)
      than in the younger (2- and 8-month-old) groups of rats, consistent with an
      impairment of hypothalamic-pituitary-adrenal axis function in older animals.
      Steady state mRNA levels of mineralocorticoid and glucocorticoid receptors were
      significantly decreased in the hippocampus of the 8-, 18-, and 24-month-old rats,
      compatible with maturational, rather than senescent, changes. CRF mRNA levels in
      the paraventricular nucleus of the hypothalamus, CRF content, and in vitro
      secretion by whole explanted hypothalami were progressively and significantly
      reduced with age, whereas the steady state levels of arginine vasopressin mRNA
      were significantly increased with age. Steady state levels of POMC mRNA were
      decreased, and ACTH content and in vitro secretion by corticotrophs were
      increased with age in the anterior pituitary. We conclude that male Fischer 344/N
      rats show a progressive hypothalamic CRH deficiency with advancing age, which
      appears to be associated with elevated production of arginine vasopressin in the
      hypothalamus.

PMID- 8137723
TI  - Effects of long-term orchidectomy on in vitro pulsatile gonadotropin-releasing
      hormone release from the medial basal hypothalamus of the adult guinea pig.
AB  - There is ample evidence provided by in vivo studies that orchidectomy increases
      the frequency of episodic GnRH release from the hypothalamus, but the effects on
      other aspects of pulsatile GnRH secretion are less well defined. We used a
      continuous superfusion system to study the effects of long term (4 weeks)
      orchidectomy or sham castration on in vitro release of GnRH from the
      retrochiasmatic medial basal hypothalamus (MBH) of the adult male guinea pig. RIA
      of GnRH in 5-min fractions (750 microliters) of superfusion medium collected
      during a 540-min observation period revealed a clearly episodic pattern (Ultra
      pulse analysis algorithm) of GnRH secretion for the MBHs of both orchidectomized
      (n = 15) and sham-operated animals (n = 15). Pulse frequency was significantly
      higher (P < or = 0.01) after orchidectomy than after sham castration (mean +/-
      SEM pulse intervals of 32.5 +/- 2.7 and 57.8 +/- 5.1 min, respectively; pulse
      analysis at 3 coefficient of variation threshold). The mean amplitude of all
      pulses (15.8 +/- 0.8 vs. 15.2 +/- 1.1 pg/750 microliters) and mean GnRH output
      (8.2 +/- 1.3 vs. 6.7 +/- 1.3 pg/750 microliters) were not significantly different
      between the two groups. Exposure for 30 min to 20 microM veratridine, a
      depolarizing agent, toward the end of the experiment resulted in a significant
      increase in GnRH output (P < or = 0.01) in both groups. The latter response was
      somewhat greater for the MBHs of orchidectomized animals (P < or = 0.01 for
      absolute response; nonsignificant for percent response), notwithstanding a 50%
      reduction of the total GnRH content of the MBH explants (P < or = 0.0001). The
      results of the present study provide further support for the view that
      retardation of the GnRH pulse generator frequency is the major mechanism by which
      the testicular hormones exert, at the hypothalamic level, their negative feedback
      action on gonadotropin secretion.

PMID- 8137724
TI  - Time course of recovery of spermatogenesis and Leydig cell function after
      cessation of gonadotropin-releasing hormone antagonist treatment in the adult
      rat.
AB  - This study examined the time course of recovery of spermatogenesis and its
      relationship to the temporal changes in circulating levels of gonadotropin and
      testosterone (T) and intratesticular T levels after cessation of treatment with a
      potent GnRH antagonist (GnRH-A). Adult male rats were given a daily sc injection
      of Nal-Glu-GnRH antagonist (1250 micrograms/kg BW) for 4 weeks and killed in
      groups of five 0, 1, 2, 3, 4, and 6 weeks after discontinuation of treatment.
      After cessation of treatment, plasma FSH levels returned to control values by 6
      weeks, whereas LH levels returned to control values within 1 week. Both
      circulating as well as intratesticular levels of T returned to normal levels by 3
      and 4 weeks, respectively. Interestingly, a rebound in both FSH and
      intratesticular T, but not in plasma T, beyond control levels occurred early in
      the recovery phase. The total volume of Leydig cells, which was only 15% of
      control values, increased 4.3-fold within 1 week and was not significantly
      different from control values (92% recovery) by 2 weeks posttreatment.
      Enumeration of earlier phases of germ cells as well as homogenization-resistant
      advanced (steps 17-19) spermatids revealed a progressive increase in germ cell
      numbers with time. Complete restoration of the numbers of preleptotene
      spermatocytes, pachytene spermatocytes, step 7 spermatids, and advanced
      spermatids occurred 1, 3, 4, and 6 weeks, respectively, after termination of GnRH
      A treatment. There was also a complete reversal of GnRH-A-induced changes in
      testicular weight, tubule diameter, and volume of seminiferous tubules and their
      lumens by 6 weeks posttreatment, paralleling the recovery of spermatogenesis.
      These results suggest that 1) complete recovery of spermatogenesis and various
      other testicular parameters can be achieved in GnRH-A-treated rats after
      cessation of treatment; 2) the progression of various germ cells during the
      recovery period follows the normal time schedule of germ cell development; and 3)
      the recovery of spermatogenesis is preceded by supranormal levels of FSH and
      intratesticular T. These findings further emphasize the suitability of
      antagonistic analogs of GnRH for male fertility control.

PMID- 8137725
TI  - Neuropeptide-Y potentiates the secretion of vasopressin from the
      neurointermediate lobe of the rat pituitary gland.
AB  - Neuropeptide-Y (NPY) is colocalized with vasopressin and oxytocin in
      magnocellular neurons of the hypothalamo-neurohypophysial system, and a very high
      density of NPY-binding sites is present within the neurohypophysis. To
      investigate the possibility that NPY exerts a modulatory role on the release of
      neurohypophysial hormones, we have studied the actions of NPY on potassium-evoked
      release of vasopressin and oxytocin from the rat neurointermediate lobe in vitro.
      NPY dose-dependently potentiated vasopressin release evoked by high extracellular
      potassium (56 mM), with a maximal enhancement of 223% (10(-7) M NPY). A similar
      effect was obtained with the Y2-selective agonist NPY-(13-36). In contrast, no
      effect on the potassium-evoked release of oxytocin was observed at this
      concentration. In the absence of Ca2+ in the incubation medium, NPY did not
      potentiate vasopressin secretion, indicating that the effect of NPY on potassium
      evoked secretion of neurohypophysial vasopressin is critically dependent on
      extracellular calcium ions. The number of neurohypophysial NPY-binding sites is
      drastically down-regulated in animals subjected to chronic osmotic stimulation.
      In the present study, it was observed that the potentiating effect of NPY on
      vasopressin secretion was completely abolished in neurointermediate lobes
      recovered from animals that had been drinking 2% NaCl for 12 days, reflecting the
      concomitant down-regulation of neurohypophysial NPY-binding sites observed during
      this state. Finally, it was confirmed that stimulation by high K+ significantly
      evoked the release of endogenous NPY from neurointermediate lobes of the
      pituitary gland. The present results provide evidence that NPY selectively and
      potently enhances evoked vasopressin secretion. Considering the coexistence of
      the two neuropeptides in magnocellular hypothalamo-neurohypophysial neurons, this
      action is likely to be part of an autostimulatory feedforward loop. NPY may be an
      important component in the mechanisms associated with the control of body fluid
      homeostasis.

PMID- 8137726
TI  - Gender-specific, maturation-dependent effects of testosterone on chondrocytes in
      culture.
AB  - This study examined the effects of testosterone on chondrocytes in vitro in order
      to determine whether the effects of testosterone were dependent on the stage of
      chondrocyte maturation and gender specific. Cells derived from male or female rat
      costochondral growth zone and resting zone cartilage were used as the cell
      culture model. [3H]Thymidine incorporation, cell number, alkaline phosphatase
      specific activity, and percent collagen production were used as indicators.
      Alkaline phosphatase specific activity in matrix vesicles and plasma membranes
      isolated from male and female chondrocyte cultures was measured to determine
      which membrane fraction was targeted by the hormone. The role of fetal bovine
      serum in the culture medium was also addressed. The results demonstrated that
      testosterone decreases cell number and [3H]thymidine incorporation in male
      chondrocytes, suggesting that it may promote differentiation of these cells.
      Alkaline phosphatase specific activity is stimulated in growth zone cells, with
      no effect on resting zone cells. The increase in enzyme activity is targeted to
      the matrix vesicles. Cells cultured in serum-free medium exhibit a dose-dependent
      inhibition of alkaline phosphatase activity when cultured with testosterone, even
      in the presence of phenol red. Testosterone-dependent stimulation of enzyme
      activity is seen only in the presence of serum, suggesting that serum factors are
      also necessary. Testosterone increased the percent collagen production in male
      cells only, regardless of the cartilage zone of origin. The results of this study
      indicate that the effects of testosterone are dependent on the time of exposure,
      presence of serum, and sex and stage of maturation of the chondrocytes.
      Testosterone-dependent stimulation of alkaline phosphatase specific activity is
      targeted to matrix vesicles.

PMID- 8137727
TI  - Calcium and a mitochondrial signal interact to stimulate phosphoinositide
      hydrolysis and insulin secretion in rat islets.
AB  - Fuel metabolism generates multiple signals that interact to stimulate insulin
      secretion. These studies explored the mechanism by which fuels activate
      phosphoinositide (PI) hydrolysis and the role of this signal transduction pathway
      in fuel-stimulated insulin secretion. High potassium (30 mM), which depolarizes
      the membrane and increases Ca2+ influx, caused only a transient monophasic
      release of insulin. In contrast, glucose (20 mM) or monomethylsuccinate (MMSucc;
      10 mM) markedly stimulated a sustained insulin secretory response, indicating
      that fuel metabolism generates a signal(s) in addition to Ca2+ influx that is
      required for a sustained secretory response. On the other hand, diazoxide, an ATP
      sensitive K+ channel activator that prevents membrane depolarization and Ca2+
      influx in response to fuel metabolism, reduced the secretory responses to glucose
      and MMSucc to baseline levels, demonstrating that Ca2+ influx was essential to
      fuel-stimulated insulin secretion. The further addition of high K+ bypassed the
      diazoxide block and restored insulin secretory rates. The insulin secretory
      response to glucose or MMSucc in the presence of diazoxide and K+ was inhibited
      by the Ca2+ channel antagonist nitrendipine and the protein kinase-C inhibitor
      staurosporine. Changes in PI hydrolysis paralleled those in insulin secretion.
      High potassium alone induced only a modest 2.5-fold increase in inositol
      phosphate accumulation. This response was significantly less than that to glucose
      or MMSucc, which increased inositol phosphate accumulation by 6.8- or 5.2-fold,
      respectively. Like its effect on secretion, diazoxide markedly reduced glucose-
      or MMSucc-stimulated PI hydrolysis, and this inhibition was reversed with high
      K+. In contrast, diazoxide had no effect on receptor-activated PI hydrolysis
      stimulated by 100 nM cholecystokinin (CCK), and the effects of CCK were not
      dependent on added fuel, indicating that fuel and CCK activate PI hydrolysis by
      distinct pathways. These findings demonstrate that mitochondrial metabolism of
      glucose or MMSucc generates a signal(s) that interacts with Ca2+ influx to
      stimulate PI hydrolysis and sustained insulin secretion. This pathway of fuel
      activated PI hydrolysis is distinct from that of CCK receptor-activated PI
      hydrolysis. These studies suggest that fuel-activated PI hydrolysis plays an
      important role in fuel-stimulated insulin secretion.

PMID- 8137728
TI  - Localization of insulin-like growth factor-I (IGF-I) and -II messenger
      ribonucleic acid and type 1 IGF receptors in the ovine uterus during the estrous
      cycle and early pregnancy.
AB  - Insulin-like growth factor-I (IGF-I), IGF-II, and the type 1 IGF receptor (IGF
      IR) gene transcripts were localized in sections of ovine uterus collected from 53
      ewes at different stages during the estrous cycle and the first 3 weeks of
      pregnancy using in situ hybridization with synthetic oligonucleotides. Binding
      studies on cryostat sections using [125I]IGF-I or [125I]des(1-3)IGF-I were
      carried out to assess whether binding sites for IGF-I colocalized with sites of
      IGF-IR gene transcription. Peak IGF-I mRNA concentrations occurred at estrus in
      both the periepithelial endometrial stromal cells and the longitudinal and
      circular muscle cells of the myometrium. Concentrations of transcript returned to
      basal levels by 48 h after estrus. The variations in IGF-I mRNA concentration
      during the estrous cycle showed significant correlations with the estradiol
      receptor concentration in the same cell types, measured in the same animals by
      immunocytochemistry (P < 0.01). IGF-II mRNA was localized exclusively to the
      caruncular stroma (high transcription) and endometrial stroma (low
      transcription), with levels showing no positive correlation to the concentration
      of estradiol receptors, progesterone receptors, or plasma progesterone, but
      decreasing gradually between estrus and days 14-15 (P < 0.05). IGF-IR mRNA was
      localized mainly to the deep and superficial glandular epithelium, with lower
      levels of transcription in the caruncular stroma and myometrium. Transcription in
      the deep glands remained high throughout the cycle, but in the superficial glands
      and myometrium, a small peak occurred in the early luteal phase (days 1-2), 24-48
      h after peak IGF-I gene transcription. [125I]IGF-I- and des(1-3)IGF-I-binding
      sites colocalized with sites of IGF-IR gene transcription. Additional binding
      sites were revealed with the iodinated ligands in the myometrium, superficial
      glands, deep stroma, and blood vessel walls, which were probably attributable to
      the presence of binding proteins (IGFBPs). The different affinities of des(1
      3)IGF-I for IGFBP-3, -2, and -1 lead us to suggest that IGFBP-2 and/or -1 are
      present in the deep stroma and glands, whereas IGFBP-3 may be responsible for the
      additional binding sites in the myometrium and blood vessel walls. Comparisons
      between pregnant and nonpregnant ewes on days 2-15 after estrus did not reveal
      any clear pregnancy-associated differences in either the sites or levels of IGF
      I, IGF-II, or IGF-IR gene transcription.

PMID- 8137729
TI  - Desethylamiodarone is a noncompetitive inhibitor of the binding of thyroid
      hormone to the thyroid hormone beta 1-receptor protein.
AB  - It has been hypothesized that amiodarone (A), a potent antiarrythmic and
      antianginal drug, induces a local hypothyroid-like condition in extrathyroidal
      tissues. This might be related to competitive antagonism of A for the thyroid
      hormone receptor reported in some studies but denied in others. These conflicting
      results are presumably due to the poor solubility of A in a hydrophilic
      environment. We, therefore, studied the effect of the drug and its major
      metabolite, desethylamiodarone (DEA), on the in vitro binding of thyroid hormone
      (T3) to its receptor protein using the rat beta 1-thyroid hormone receptor
      expressed in Escherichia coli. A and DEA stayed in solution up to 10(-4) M when
      0.05% Triton X-100 was added to the incubation buffer, as evidenced by a recovery
      of 80-90% for both chemicals, as measured by HPLC. DEA, but not A, had a clear
      inhibitory effect on the binding of T3 to its receptor (IC50, 1-3 x 10(-5) M).
      Scatchard analysis in the presence of DEA demonstrated a dose-dependent decrease
      in the Ka as well as the maximum binding capacity. Lineweaver-Burke analysis
      indicated noncompetitive inhibition. Plots of the intercepts of Lineweaver-Burke
      plots vs. DEA concentration were linear (y = 0.334 + 0.098x), giving a Ki of 30
      microM for the binding of DEA to the occupied receptor. Plots of the slopes vs.
      inhibitor concentration were parabolic (y = 3.01 + 0.06x + 0.16x2), indicating a
      progressively stronger effect of DEA on the unoccupied receptor as concentrations
      rise. This preference for the unoccupied receptor is reflected in experiments
      that show a progressive loss of T3 binding when the receptor was incubated for
      increasing periods with DEA before adding T3. We conclude that DEA is a
      noncompetitive inhibitor of the binding of T3 to the beta 1-thyroid hormone
      receptor protein, interacting preferably with the unoccupied T3 receptor.

PMID- 8137730
TI  - Is the renal type III corticosteroid-binding site the collecting duct-specific
      isoform of 11 beta-hydroxysteroid dehydrogenase?
AB  - In addition to mineralocorticoid and glucocorticoid receptors, the kidney
      contains a third high affinity binding site for endogenous glucocorticoids, the
      type III receptor. These binding sites have been localized to the collecting
      duct, but their biological function has not yet been identified. We have used
      immunodissected rabbit cortical collecting duct (CCD) cells to further
      characterize these binding sites. Experiments using intact cells revealed very
      high levels of [3H]corticosterone (CS) binding (2.99 +/- 0.38 x 10(6)
      sites/cell), about 100-fold higher than the number of mineralocorticoid or
      glucocorticoid receptors in CCD cells. Among the two cell types of the collecting
      duct, principal cells, the putative targets of aldosterone, contain approximately
      10 times more CS-binding sites than intercalated cells. The Kd of the binding
      sites for CS averaged 54.3 +/- 3.48 nM at 0 C. The relative affinity of unlabeled
      steroids for the binding sites is CS > carbenoxolone congruent to glycyrrhetinic
      acid > or = 11-dehydrocorticosterone (11-DHCS) > cortisol congruent to cortisone
      > deoxycorticosterone > progesterone. Synthetic glucocorticoids (dexamethasone,
      RU 28362, and RU 486) and aldosterone did not compete for [3H]CS binding. Based
      on their preferential localization to CCD cells, which are the main targets of
      aldosterone, we hypothesized that these CS-binding sites are involved in
      conferring aldosterone specificity on mineralocorticoid receptors in these cells.
      As 11 beta-hydroxysteroid dehydrogenase (11-OHSD) is thought to play a key role
      in this process, we studied the relationship between CS-binding sites and the
      collecting duct isoform of this enzyme (11-OHSD/CD) in purified CCD cells.
      Freshly isolated cells rapidly converted [3H]CS to 11-DHCS with an apparent Km of
      about 50 nM, a value close to the Kd of the CS-binding sites for CS in these
      cells. The rank order of potency of unlabeled steroids to decrease the conversion
      of [3H]CS to [3H]11-DHCS was identical to their relative affinity for the CS
      binding sites. Also, there is a close correlation (r = 0.783; P < 0.0001) between
      the activity of 11-OHSD and the number of CS-binding sites in different CCD
      preparations. Based on the similarities between the abundant CS-binding sites and
      avid CS metabolism in CCD cells, we suggest that these binding sites belong to
      the collecting duct isoform of 11-OHSD, which, by decreasing the intracellular
      levels of active glucocorticoids, plays an important role in conferring
      aldosterone selectivity on mineralocorticoid receptors in CCD cells.

PMID- 8137731
TI  - Glycosylation of thyroglobulin secreted by porcine cells cultured in chamber
      system: thyrotropin controls the number of oligosaccharides and their anionic
      residues.
AB  - Porcine thyroid cells were cultured in porous bottom chambers in the presence or
      in the absence of TSH added to the basal medium. Radiolabeled-sugar (3H-mannose)
      was added to the basal medium on day 11 for 4 days and the glycosylation of
      thyroglobulin (Tg), the major glycoprotein secreted into the apical medium, was
      studied. The incorporation of 3H-mannose per molecule of Tg was increased 1.5
      fold by a 50 microU/ml minimal concentration of TSH. The distribution of
      glycopeptides (after pronase digestion) on concanavalin A sepharose column was
      not modified by the presence of TSH. However this distribution was different from
      that observed for Tg extracted from gland (more multiantennary units than
      biantennary units and polymannose units). After desialylation and desulfation,
      the sizes of the oligosaccharide chains analyzed on HPLC appeared similar when
      cells were cultured under stimulation or not. Thus TSH enhanced sugar
      incorporation without modifying either the distribution of the different
      oligosaccharide moieties or their sizes. Consequently the effect of TSH was a 1.5
      fold increase in oligosaccharide chains linked to asparagine residues. 3H-Mannose
      oligosaccharide chains were then analyzed on ion-exchange HPLC before and after
      desialylation and desulfation. The number of anionic residues per oligosaccharide
      unit (particularly sulfate residues) was higher in the absence of TSH than in the
      presence of TSH. Nevertheless, since TSH increased the number of carbohydrate
      units per molecule of Tg 1.5-fold, the total content of anionic residues bound to
      oligosaccharide units per molecule of Tg seems not to be modified by TSH.

PMID- 8137732
TI  - Multihormonal regulation of dehydroepiandrosterone sulfotransferase messenger
      ribonucleic acid levels in adult rat liver.
AB  - Hydroxysteroid sulfotransferases (DHEA ST) represent a family of enzymes that
      catalyze the conversion of dehydroepiandrosterone and other 3 beta
      hydroxysteroids into more hydrophilic water-soluble sulfate conjugates. The
      present study was designed to investigate the regulation of hepatic DHEA ST
      expression by sex steroids and pituitary hormones, namely GH and PRL, in both
      male and female rats. DHEA ST mRNA levels were measured by dot blot hybridization
      using a 332-basepair fragment of rat DHEA ST (ST-20) cDNA as a probe. Hepatic
      DHEA ST mRNA levels were 2.8-fold higher in females than in males. A 15-day
      gonadectomy did not affect DHEA ST mRNA levels in the male liver; in females, a
      35% decrease in DHEA ST mRNA levels compared with those in intact controls was
      observed. Administration of 17 beta-estradiol (E2; 1 microgram/kg, twice daily)
      alone had no effect on the accumulation of DHEA ST mRNA, but the same treatment
      completely reversed the marked inhibitory effect of dihydrotestosterone (DHT; 400
      micrograms/kg, twice daily) on this parameter in both gonadectomized males and
      females. In female rats, 24-day hypophysectomy (HYPOX) decreased DHEA ST mRNA
      levels by 62%, whereas no change was detected in males. In HYPOX animals,
      treatment with E2 or DHT for 9 days starting 15 days after surgery had no effect
      on hepatic DHEA ST mRNA levels in rats of both sexes. In intact males, the
      presence of pituitary implants under the kidney capsule increased DHEA ST mRNA
      levels by 190% (above the control), which reached levels similar to those in
      intact females, whereas pituitary implants exerted no effect on this parameter in
      intact females. However, treatment of HYPOX rats with ovine PRL (oPRL; 4 mg/kg,
      twice daily) had no significant effect on the accumulation of DHEA ST mRNA in
      male and female animals. In HYPOX females, administration of rat GH (80
      micrograms/kg, twice daily) had no effect on DHEA ST mRNA levels, whereas
      continuous infusion of rat GH (3.6 micrograms/h), using osmotic minipumps to
      mimic the female GH secretory pattern, increased this parameter by 290% (above
      the control value), thus completely reversing the effect of hypophysectomy. In
      HYPOX males, both modes of GH administration increased DHEA ST mRNA levels by 70
      90% (above the control). The present study demonstrates that in both
      gonadectomized male and female rats, administration of E2 completely blocks the
      marked inhibitory effect of DHT on hepatic DHEA ST mRNA levels.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8137733
TI  - Direct measurement of whole body thyroid hormone pool sizes and interconversion
      rates in fasted rats: hormone regulation implications.
AB  - Food deprivation markedly reduces thyroid hormone levels in mammalian plasma, but
      existing data are incomplete and equivocal regards extrathyroidal hormone
      production and other indices of overall hormone economy. We have used a novel
      experiment design and analysis to directly measure the whole-body rate of
      conversion of T4 into T3 and several other steady-state whole organism
      parameters, in 4-day fasted and fed control rats. Trace amounts of 125I-labeled
      T3 (T3) or T4 (T*4) were infused for 7 days from osmotic minipumps implanted sc.
      On day 7, rats were anesthetized, bled, and killed and carcasses were frozen in
      liquid N2, pulverized, homogenized, and extracted. Extracts and plasma samples
      were chromatographed on both Sephadex and HPLC. Tracer infusion rates, whole rat
      tissue weights, and steady state tissue, blood, and plasma T*3, T*4, and total
      radioactivity concentrations provided all kinetic parameters of interest from
      simple steady state computations. T4 secretion (SR4) and whole body pool sizes
      were reduced 49-55% in fasted rats. But the most notable results were that the
      percent of available extrathyroidal T4 converted to T3 in fasted [41.6 +/- 7.9%
      (SD)] was 87% greater than that in the fed (22.3 +/- 7.69%) rats and this, in
      turn, generated an absolute rate of production of T3 from T4 not significantly
      different in fasted vs. fed controls (7.17 +/- 2.40 vs. 7.54 +/- 3.10 ng/h.100 g
      BW). The surprisingly high 42% conversion ratio in fasting is explained in part
      by larger T3 blood pools (which are not sites of T3 production from T4) relative
      to tissue T3 pools in fasted rats, not accounted for in earlier whole-body
      studies. In contrast with this finding of an increased T4 to T3 conversion ratio
      in fasted rats, based on whole body measurements, T3 plasma concentrations (Cp3),
      clearance rates (PCR3), appearance rates (PAR3 = PCR3Cp3), and more conventional
      indirect estimates of the T4 to T3 conversion ratio (100 PAR3/SR4) were all
      substantially reduced, consistent with reports in fasting humans limited to
      measurements of T3 and T3 turnover in plasma and interpreted as indicative of
      reduced whole body T4 or T3 conversion. Directly measured total T3 extrathyroidal
      distribution volumes, reduced 55% in the fasted group from 241 +/- 19.5 to 109 +/
      8.14 ml/100 g BW, are also of interest because fed rat values are 27-61% greater
      than virtually all previous estimates of this index of total body T3.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8137734
TI  - Effects of 1,25-dihydroxyvitamin D3 on proliferation and differentiation of Caco
      2 cells.
AB  - The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or calcitriol, on the
      proliferation and differentiation of Caco-2 cells was studied. Vitamin D receptor
      mRNA was detected in both pre- and postconfluent cells, and its abundance was
      unchanged with time and in response to calcitriol. 1,25-(OH)2D3-binding activity
      increased during differentiation, but there was no difference in binding between
      1,25-(OH)2D3-treated and control cells. 1,25-(OH)2D3 caused a dose-dependent
      reduction in proliferation, as assessed by [3H]thymidine incorporation and DNA
      content. 1,25-(OH)2D3 significantly enhanced the normal rise in alkaline
      phosphatase activity during differentiation and increased alkaline phosphatase
      mRNA abundance. In contrast, 1,25-(OH)2D3 inhibited the normal rise in sucrase
      isomaltase activity and the corresponding mRNA level, although the inhibition
      occurred after the initial period of cell differentiation (> 10 days
      postplating). Morphological analysis demonstrated that by day 12 postplating,
      1,25-(OH)2D3 increased the mean dome diameter and microvillus length and density.
      Although 1,25-(OH)2D3 decreases the proliferation of Caco-2 cells and enhances
      certain parameters of differentiation, not all brush-border hydrolases respond in
      a similar fashion, making it necessary to interpret with caution their individual
      use as markers of differentiation.

PMID- 8137735
TI  - Involvement of the catecholaminergic input to the paraventricular nucleus and of
      corticotropin-releasing hormone in the fasting-induced suppression of luteinizing
      hormone release in female rats.
AB  - The roles of the adrenergic projection to the paraventricular nucleus (PVN) and
      of central CRH in the suppression of pulsatile LH secretion during 48-h fasting
      were examined in ovariectomized estradiol (E2)-treated rats. The animals were
      ovariectomized and immediately implanted with Silastic tubing containing E2. One
      week after ovariectomy and E2 implantation, the animals were implanted
      stereotaxically with a guide cannula for microinjection into the PVN or
      intracerebroventricular (icv) injection. One week later, some of the animals were
      deprived of food for 48 h. The unfasted controls were provided with food ad
      libitum. At this point, blood samples were collected every 6 min for 3 h. Animals
      received an injection of 50 micrograms alpha-methyl-p-tyrosine (AMPT), a
      catecholamine synthesis inhibitor, into the PVN 3 h before the sampling started
      or an icv injection of 26 nmol alpha-helical CRF-(9-41), a CRH antagonist, after
      the first hour of blood sampling; control animals were given the vehicle at the
      equivalent time. The fasted animals injected with AMPT showed a significantly
      higher mean LH concentration and LH pulse frequency over the 3-h sampling period
      compared with the vehicle-injected controls. Treatment with AMPT had no
      significant effect on LH secretion in unfasted animals. The icv injection of
      alpha-helical CRF-(9-41) reinstated the suppressed LH release in fasted rats, but
      had no significant effect in unfasted animals. These results suggest that the
      adrenergic projection to the PVN and central CRH are involved in the suppression
      of pulsatile LH release during food deprivation. The possibility that fasting
      activates an ascending adrenergic projection that stimulates CRH release and thus
      suppresses pulsatile LH secretion is discussed.

PMID- 8137736
TI  - The coupling of multiple signal transduction pathways with steroid response
      mechanisms.
AB  - In a human breast carcinoma-derived cell line engineered to contain a hormone
      responsive luciferase reporter gene, manipulation of cell growth conditions or
      cellular signal transduction in a variety of ways can enhance or impair
      glucocorticoid-mediated induction of a target gene. Induction may be enhanced as
      much as 10-fold or inhibited 90% by different treatments. For example, two
      different inhibitors of protein phosphatase-1 and -2A potentiated the hormone
      dependent induction of luciferase. Activation of protein kinase-A via addition of
      8-bromo-cAMP or forskolin also potentiated the hormonal induction, whereas 8
      bromo-cGMP was ineffective. In contrast, activating protein kinase-A by
      inhibiting cAMP turnover with the phosphodiesterase inhibitors
      isobutylmethylxanthine or Ro20-1724 inhibited the hormone response rather than
      potentiated it. The inhibitory activity of isobutylmethylxanthine was evident
      even when activators of protein kinase-A are administered simultaneously.
      Isobutylmethylxanthine must, therefore, activate a signal transduction pathway in
      addition to the protein kinase-A pathway. Activation of protein kinase-C
      potentiated the hormone response in a cell-specific manner. Treatment with
      epidermal growth factor and imposition of cell stress by heat shock or inhibition
      of protein synthesis also enhanced the glucocorticoid response. Thus, our results
      suggest an elaborate coupling of the steroid response pathway with other cellular
      signal transduction mechanisms that permits an additional layer of control to be
      imposed on hormone-mediated transcriptional responses. It is proposed that cell
      specific phosphorylation events influence steroid receptor interaction with the
      basal transcription apparatus, thereby altering receptor-mediated induction
      mechanisms.

PMID- 8137737
TI  - Parathyroid hormone increases the expression of receptors for epidermal growth
      factor in UMR 106-01 cells.
AB  - PTH administration in vivo increases osteoblast number and activity, resulting in
      increased bone formation, and also increases osteoclast-mediated bone resorption.
      Studies in vitro, however, have shown that the actions of PTH on osteoblast-like
      cells are inhibitory and catabolic, as shown by decreases in growth rate and
      collagen synthesis and increases in collagenase production. The present studies
      were designed to investigate possible mechanisms for these observations by
      examining the effects of PTH on the response of osteoblast-like cells to the
      osteoblast growth factor, epidermal growth factor (EGF). Confluent cultures of
      UMR 106-01 cells were treated with rat PTH-(1-34) for periods up to 72 h, and EGF
      receptors were measured with [125I]EGF. PTH, in a dose- and time-dependent
      manner, increased the number of EGF receptors 2-fold. The half-maximal effect of
      PTH occurred at a concentration of 1 nM, the same PTH concentration that resulted
      in half-maximal increases in cAMP generation. The increase in EGF binding was
      associated with an enhanced biological effect, as shown by augmentation of EGF
      stimulated diglyceride production. The effect of PTH could be reproduced by the
      addition of 8-bromo-cAMP, but not by the phorbol ester phorbol myristate acetate.
      In the presence of cyclohexamide, the effect of PTH on EGF binding was abolished,
      suggesting that new protein synthesis was required to increase the number of EGF
      receptors. Northern blots of total RNA, using a cDNA probe encoding the
      extracellular domain of the rat EGF receptor, revealed that PTH treatment
      resulted in a 2- to 3-fold increase in the level of EGF receptor mRNA. These data
      suggest that the proliferative effects of PTH on the osteoblast may be mediated
      indirectly by a PTH-induced increase in the number of EGF receptors.

PMID- 8137738
TI  - Parathyroid-responsive modifications in the nuclear matrix of ROS 17/2.8 rat
      osteosarcoma cells.
AB  - PTH is a mediator of skeletal development and remodeling that influences gene
      expression in osteoblastic cells. It is well established that PTH modulates the
      activity of membrane-associated second messenger signal transduction pathways. In
      these studies we have addressed the potential contribution of components of cell
      structure to the integration of PTH-related regulatory signals that influence the
      expression of bone cell genes. Chronic treatment of ROS 17/2.8 rat osteosarcoma
      cells with PTH is accompanied by changes in gene expression that are at least in
      part transcriptionally controlled. To explore the involvement of nuclear
      architecture in PTH-responsive modifications in gene expression, we investigated
      changes in the nuclear matrix after PTH treatment. Consistent with a role for the
      nuclear matrix in determining spatial organization and topology of chromatin as
      well as in the localization and targeting of transcription factors, we observed
      PTH-associated changes in a 200-kilodalton nuclear matrix protein in response to
      PTH. A significant down-regulation of synthesis was observed when nuclear matrix
      proteins were resolved electrophoretically in two-dimensional gels. This protein
      was restricted to the nuclear matrix and was not detected in the chromatin or
      cytoskeletal cellular fractions. These alterations in nuclear matrix proteins
      that occur after PTH treatment in osteosarcoma cells were phenotype related. They
      did not occur in UMR-106 POL or H4 hepatoma cells. Our findings support a role
      for the nuclear matrix in transducing PTH-mediated regulatory signals to
      facilitate the extent to which genes in osteoblasts are transcribed.

PMID- 8137739
TI  - The effect of protein kinases on desensitization of the porcine follicular
      membrane luteinizing hormone/chorionic gonadotropin-sensitive adenylyl cyclase.
AB  - Because the acute homologous phase of desensitization of the LH/CG-sensitive
      adenylyl cyclase in porcine follicles is readily demonstrated in a cell-free
      membrane preparation, it follows that any enzyme(s) required to achieve
      desensitization must be present in the membranes and must be activated upon LH/CG
      receptor activation. The purpose of the following studies was to determine
      whether modulation of endogenous membrane protein kinases, with activators or
      inhibitors, or addition of exogenous protein kinases affected desensitization of
      the LH/CG-sensitive adenylyl cyclase. The effects of these potential modulators
      were evaluated in both the presence and absence of ligand (hCG)-stimulated
      receptor activation. To this end, membranes were incubated in the presence or
      absence of hCG (stage 1) and then assayed for adenylyl cyclase activity in the
      presence or absence of hCG (stage 2). The results showed that although porcine
      follicular membranes rich in LH/CG-sensitive adenylyl cyclase activity also
      exhibited cAMP-dependent [protein kinase-A (PKA)], cGMP-dependent (PKG), lipid
      dependent (PKC), Ca2+/calmodulin, and casein kinase-I and -II activities, only
      full hCG-stimulated adenylyl cyclase activity (measured with BSA in stage 1 and
      hCG in stage 2) was reduced upon addition of exogenous PKC (to the stage 1
      incubation). hCG-dependent desensitization of cAMP synthesis (measured with hCG
      in stages 1 and 2) was unaffected by activators or inhibitors of endogenous PKA,
      PKC, or PKG, by an inhibitor of casein kinases and kinases in the beta-adrenergic
      receptor kinase family, or by the addition of exogenous active PKA, PKC, or
      rhodopsin kinase to the stage 1 incubation. These results suggest that the acute
      homologous phase of hCG-dependent desensitization of adenylyl cyclase activity in
      follicular membranes is not regulated by PKA, PKC, PKG, or messenger-independent
      heparin-sensitive protein kinases.

PMID- 8137740
TI  - Growth hormone and parathyroid hormone stimulate intestinal calcium absorption in
      aged female rats.
AB  - Aged (16-month-old) female rats (n = 8/treatment) were injected for 12 days with
      GH (100 micrograms/100 g x day), PTH (8 micrograms/100 g x day), GH plus PTH, or
      vehicle (V) in an experiment designed to determine the effects of these hormones
      on intestinal mineral absorption in senescent rats. PTH and GH increased
      fractional net calcium absorption to a similar extent (PTH, 1.6-fold; GH, 1.4
      fold) even though PTH increased serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 3.7
      fold, and GH had no significant effect. GH plus PTH caused no further increase in
      serum 1,25-(OH)2D3 above that caused by PTH alone, but resulted in an additive
      effect on net calcium absorption (2.3-fold increase). PTH and GH also had
      statistically independent effects on phosphate absorption; magnesium absorption
      was elevated only by PTH. Duodenal calbindin-D9k levels were increased by GH
      (from 3.79 +/- 0.72 to 6.98 +/- 0.73 micrograms/mg protein) and PTH (from 3.23 +/
      0.46 to 7.55 +/- 0.75 micrograms/mg protein); PTH plus GH treatment resulted in
      an additive effect on calbindin-D9k levels. Additional in vitro transport studies
      in the human intestinal cell line Caco-2 showed that 72 h of pretreatment with
      the local mediator of GH action, insulin-like growth factor-I (at 10 and 100
      ng/ml), stimulated transcellular calcium transport (22% and 44%, respectively)
      regardless of concomitant 1 nM 1,25-(OH)2D3 pretreatment (80% increase). Our
      findings suggest a 1,25-(OH)2D3-mediated mechanism for PTH-induced changes in
      calcium and phosphorus absorption. In contrast, the effects of GH in the
      senescent rat are independent of changes in circulating 1,25-(OH)2D3 and our data
      suggest that these effects may be mediated by insulin-like growth factor-I.

PMID- 8137741
TI  - Increased renal 25-hydroxyvitamin D3-24-hydroxylase messenger ribonucleic acid
      and immunoreactive protein in phosphate-deprived Hyp mice: a mechanism for
      accelerated 1,25-dihydroxyvitamin D3 catabolism in X-linked hypophosphatemic
      rickets.
AB  - X-Linked Hyp mice exhibit rachitic bone disease, hypophosphatemia, impaired renal
      phosphate reabsorption, and abnormal regulation of renal 1,25-dihydroxyvitamin D3
      [1,25-(OH)2D3] metabolism. We demonstrated that phosphate deprivation of Hyp
      mice, but not normal littermates, elicits a dramatic fall in serum 1,25-(OH)2D
      levels and an increase in renal 1,25-(OH)2D3 catabolism that can be ascribed to
      an increase in the activity of renal mitochondrial 25-hydroxyvitamin D3-24
      hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway. The
      present study was undertaken to elucidate the mechanism for the increase in renal
      24-hydroxylase activity in phosphate-deprived Hyp mice. Phosphate deprivation of
      Hyp mice resulted in a 3-fold increase in the maximum velocity for 24-hydroxylase
      (n = 5; P < 0.001) accompanied by an increase in 24-hydroxylase immunoreactive
      protein relative to the level of ornithine aminotransferase. Phosphate
      deprivation of Hyp mice also elicited a 3-fold increase in renal 24-hydroxylase
      mRNA abundance relative to that of beta-actin mRNA (n = 7; P < 0.001). The
      increase in 24-hydroxylase mRNA was specific to the kidney and was evident as
      early as 1 day of the low phosphate diet. Phosphate deprivation had no effect on
      renal 24-hydroxylase immunoreactive protein or mRNA in normal littermates. In
      contrast to the abnormal 24-hydroxylase response to dietary phosphate, Hyp mice
      exhibited an appropriate increase in renal 24-hydroxylase mRNA and catalytic
      activity in response to increasing doses of 1,25-(OH)2D3. The present results
      demonstrate that elevated renal 24-hydroxylase activity in phosphate-deprived Hyp
      mice can be ascribed to an increase in the abundance of 24-hydroxylase mRNA and
      protein and suggest that inappropriate regulation of 1,25-(OH)2D3 catabolism in
      Hyp mice occurs at the pretranslational level.

PMID- 8137742
TI  - Control of cytosolic free calcium in cultured human pancreatic beta-cells occurs
      by external calcium-dependent and independent mechanisms.
AB  - Changes in cytosolic intracellular free Ca2+ ([Ca2+]i) in response to glucose,
      glyburide, cholinergic agonists, and elevated [K+]o (external potassium
      concentration) were measured in cultured human islet beta-cells. In the absence
      of glucose, the mean resting [Ca2+]i in single beta-cells was 84.5 +/- 4.7 nM (n
      = 86) and remained unchanged in low external [Ca2+]o (Ca2+ concentration) (< 0.2
      microM) at 23-25 C. Glucose (5.6-33 mM) induced a slow dose-related [Ca2+]i rise
      up to 300.0 +/- 50.6 nM (n = 19). This [Ca2+]i rise always occurred with a delay
      that varied from cell to cell (approximately 10-120 sec), and the steady state
      [Ca2+]i exhibited a sigmoidal dependence on glucose concentration (midpoint at
      14.9 mM). The glucose-induced rise in [Ca2+]i was attenuated by about 62% in low
      external [Ca2+]o and was not affected by dantrolene, a drug that inhibits Ca2+
      release from the endoplasmic reticulum. In the absence or presence of glucose,
      cholinergic receptor agonists evoked a biphasic increase in [Ca2+]i up to 350 nM;
      the delayed component of the [Ca2+]i rise was blocked by dantrolene. A rapid
      elevation of [K+]o to 40 mM also elicited a biphasic rise in [Ca2+]i, which
      peaked at about 250 nM and was inhibited by the Ca2+ channel antagonist
      nifedipine. Glyburide (4 microM) in the absence of glucose also induced a [Ca2+]o
      dependent rise in [Ca2+]i. Increasing the concentration of glucose from 4 to 16.7
      mM evoked a biphasic pattern of insulin secretion from perifused isolated islets
      at 37 C. Finally, in the presence of 4 mM glucose, a cholinergic muscarinic
      receptor agonist stimulated insulin secretion. A glucose-stimulated [Ca2+]i rise
      was also studied at 24 and 37 C in cultured rat islet cells. Our results suggest
      that the Ca2+ required for glucose-induced and muscarinic agonist-potentiated
      insulin release enters the cytosol from both extracellular and intracellular Ca2+
      stores.

PMID- 8137743
TI  - Effect of interleukin-1 beta on ovulation in the in vitro perfused rabbit ovary.
AB  - Interleukin-1 (IL-1), a prominent 17-kilodalton member of a group of immune
      mediators referred to as cytokines, is secreted by a variety of immuno- and
      nonimmunocompetent cells. As IL-1 is an established mediator of inflammation, and
      ovulation may constitute an inflammatory-like reaction, consideration may be
      given to the possibility that IL-1 may play an intermediary role in the ovulatory
      process. Such a hypothesis is supported by the recent demonstration of the
      gonadotropin-dependent preovulatory induction of IL-1 transcripts at the level of
      the murine and human ovary. To date, however, the direct effect of IL-1 beta on
      the ovulatory process has not been examined. The objective of this study was to
      investigate the potential role of IL-1 beta in ovulation, oocyte maturation
      (nuclear and cytoplasmic), and subsequent fertilizability of in vitro ovulated
      oocytes. Rabbit ovaries perfused in vitro were used for these experiments.
      Ovarian arteries were cannulated in situ, and the ovaries were excised and
      perfused in vitro with or without IL-1 beta (18 ng/ml). The ovulatory efficiency
      of 18 ng/ml IL-1 beta-treated ovaries was 73.1%, similar to that of hCG (71.2%).
      Recovered oocytes were examined for their maturation and were inseminated in
      vitro to investigate fertilization, cleavage, and embryonic development. The
      fertilization rates of the 18 ng/ml IL-1 beta-treated and hCG-treated groups were
      65.8% and 95.8% (P < 0.01), respectively. Cleavage rates of the IL-1 beta-treated
      and hCG-treated groups were 50% and 83.3% (P < 0.01), respectively. Most of the
      cleaved embryos from the IL-1 beta-treated group arrested at the four-cell stage,
      and only 2.6% of the fertilized embryos developed into the morula stage, whereas
      54.2% of the hCG-treated group developed to the morula stage (P < 0.01). A
      cytotoxic effect of IL-1 beta is unlikely in this model. A more likely
      explanation is the induction of other factors by IL-1 beta, which may inhibit
      cytoplasmic maturation. Taken together, our findings demonstrate that in the
      absence of an ovulatory gonadotropic trigger, IL-1 beta can induce ovulation and
      oocyte maturation, facilitate fertilization, and influence subsequent embryonic
      development. Although fertilization and embryonic development occurred after IL-1
      beta treatment, these rates were lower than those after hCG treatment. These
      observations give credence to the possibility that IL-1 may play an intermediary
      role in the ovulatory process.

PMID- 8137744
TI  - Regulation of messenger ribonucleic acid expression of 1 alpha,25
      dihydroxyvitamin D3-24-hydroxylase in rat osteoblasts.
AB  - We have reported that PTH inhibits 25-hydroxyvitamin D3-24-hydroxylase messenger
      RNA (mRNA) expression induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha, 25
      (OH)2D3] in rat kidney but not intestine. In the present study, we examined
      whether the suppression of 24-hydroxylase mRNA expression by PTH occurs commonly
      in tissues and cells which have PTH receptors. Administration of 1 alpha, 25
      (OH)2D3 into rats fed a synthetic vitamin D-repleted diet containing adequate
      calcium greatly increased serum levels of calcium and 1 alpha, 25-(OH)2D3. Also,
      there was a 4-fold increase in bone 24-hydroxylase activity in response to 1
      alpha, 25-(OH)2D3 administration. In rats fed a low calcium diet, renal 24
      hydroxylase activity was suppressed probably due to secondary
      hyperparathyroidism. In contrast, the low calcium feeding did not suppress bone
      24-hydroxylase activity. The expression of 24-hydroxylase mRNA in rat
      osteoblastic C-26 and C-11 cells was similar and attained maximal levels 24 h
      after cells were incubated with 10(-8) M 1 alpha, 25-(OH)2D3. Induction of 24
      hydroxylase mRNA expression by 1 alpha, 25-(OH)2D3 was much greater and earlier
      in immature C-26 cells than mature C-11 cells. Simultaneous addition of PTH,
      prostaglandin E2, or cAMP together with 1 alpha, 25-(OH)2D3 did not down-regulate
      mRNA expression of 24-hydroxylase induced by the vitamin in both C-26 and C-11
      cells. Of the three osteoblastic cells (C-26, C-20, and C-11) examined, C-26
      cells showed the least mRNA expression of vitamin D receptors, in spite of the
      highest expression of 24-hydroxylase mRNA. These results suggest that unlike in
      the kidney, bone 24-hydroxylase mRNA expression is not down-regulated by PTH
      despite of the presence of PTH receptors. They also suggest that the degree of
      the induction of 24-hydroxylase mRNA by 1 alpha, 25-(OH)2D3 is not explained
      simply by the vitamin D receptors content.

PMID- 8137745
TI  - Decline in immediate early gene expression in gonadotropin-releasing hormone
      neurons during proestrus in regularly cycling, middle-aged rats.
AB  - Female reproductive decline is characterized by a gradual loss of estrous
      cyclicity due in part to age-related changes in several hypothalamic
      neurotransmitter systems known to regulate reproductive function. Previously, we
      have demonstrated that in middle-aged rats that exhibited no changes in the
      regularity of their estrous cycles, the proestrous LH surge is markedly
      attenuated. To determine whether these age-related deficits involve alterations
      in GnRH neuronal activation, we examined expression of the immediate early gene
      products, c-fos and Jun, in GnRH neurons of young and middle-aged proestrous
      animals. Regularly cycling young (3- to 4-month-old) and middle-aged (10- to 12
      month-old) animals were perfused transcardially at 2300 h on diestrus or at 0230,
      0530, 0900, 1400, 1630, 1930, or 2300 h on proestrus, and the brains were
      processed for dual immunocytochemistry of c-fos or Jun and GnRH. In agreement
      with earlier studies in young rats, 34 +/- 4% of the GnRH neurons expressed c-fos
      and 40 +/- 3% expressed Jun during the proestrous LH surge (1630 and 1930 h).
      However, in the middle-aged animals, there was a dramatic decline in the number
      of GnRH neurons that expressed c-fos (9 +/- 1%) and Jun (14 +/- 1%) during the LH
      surge. There were no changes in the number of GnRH neurons between the two age
      groups. Furthermore, the strong correlation that existed between c-fos expression
      and serum LH in young animals was lost by the time the animals reached middle
      age. These data demonstrate that by the time animals reach middle age, there is a
      significant decline in the number of activated GnRH neurons, which may account
      for the decrease in the amplitude of the LH surge that precedes the onset of
      irregular estrous cycles. This could be due to either age-related changes in the
      GnRH neuron itself or in the neuronal circuitry involved in activation of these
      neurons.

PMID- 8137746
TI  - Central regulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion
      by estradiol during the period leading up to the preovulatory GnRH surge in the
      ewe.
AB  - An experiment was conducted to investigate the central regulatory effects of
      estradiol on GnRH secretion leading up to the preovulatory LH surge in the ewe.
      Midluteal phase ewes were ovariectomized, treated with steroid implants to
      maintain luteal phase concentrations of progesterone and estradiol, and fitted
      with an apparatus for collection of hypophyseal portal blood. After simulated
      luteolysis (removal of progesterone implants), the ewes were allocated to one of
      three groups: estradiol withdrawn, estradiol maintained at a luteal phase level,
      or estradiol raised from a luteal phase level to a peak follicular phase level in
      two increments. The results demonstrated that during the interval between
      luteolysis and the preovulatory gonadotropin surge, estradiol exerts a dose
      dependent suppression of GnRH secretion from the hypothalamus. This effect
      reflects a suppression of GnRH pulse size and occurs despite a stimulatory action
      of estradiol on GnRH pulse frequency. The suppressive effect of estradiol on GnRH
      secretion, however, was delayed relative to that on LH. We conclude that during
      the period leading up to the preovulatory surge in the ewe, estradiol acts
      centrally, reducing GnRH secretion by suppressing GnRH pulse size.

PMID- 8137747
TI  - Processing and targeting of a molluscan egg-laying peptide prohormone as revealed
      by mass spectrometric peptide fingerprinting and peptide sequencing.
AB  - The neuroendocrine cerebral caudodorsal cells of Lymnaea stagnalis initiate and
      coordinate ovulation and egg mass production and associated behaviors through the
      release of a complex set of peptides that are derived from the caudodorsal cell
      hormone-I (CDCH-I) precursor. We have previously characterized the CDCH-I
      peptide. In the present study, we isolated and amino acid sequenced by
      conventional peptide chemistry five additional peptides, epsilon-peptide,
      calfluxin, alpha-caudodorsal cell peptide, delta-peptide, and carboxyl-terminally
      located peptide, from the cerebral commissure, the neurohemal area of the
      caudodorsal cells. Fingerprinting by matrix-assisted laser desorption mass
      spectrometry of peptides in the commissure demonstrated the presence of all
      sequenced peptides and, in addition, could identify two other peptides derived
      from pro-CDCH-1, the beta 1- and beta 3-peptides. These findings together with
      previous immunocytochemical studies enabled us to define cleavage sites and major
      processing events of pro-CDCH-1. Pro-CDCH-1 is initially cleaved in the Golgi
      apparatus into carboxyl- and amino-terminal parts, each of which is sorted into
      distinct vesicle classes that traffic to different intracellular sites. As a
      result, in the commissure, peptides derived from the carboxyl-terminal part,
      including CDCH-1, are present at a many-fold higher concentration than those
      derived from the amino-terminal part.

PMID- 8137748
TI  - Differentially regulated immediate early genes in the rat uterus.
AB  - Estrogen stimulates cellular proliferation in the luminal epithelium, stroma, and
      smooth muscle of immature rat uterus. Progesterone administered concurrently with
      estrogen blocks the stimulatory effect of estrogen specifically in the
      epithelium, whereas progesterone administered alone stimulates proliferation in
      the endometrial stroma and myometrium. The present studies determined the effects
      of estrogen and progesterone on expression of the growth-associated, immediate
      early genes c-fos, c-jun, and jun-B in the luminal epithelium of the uterus.
      Hormonal effects were quantitated by Northern analysis of RNA extracted directly
      from the uterine luminal epithelium. Estrogen stimulated c-fos and jun-B
      expression, but repressed c-jun mRNA levels in the epithelium. In contrast, when
      whole organ RNA extracts were analyzed, estrogen increased mRNA levels for all
      three genes. Although progesterone administered alone showed no effect on mRNA
      levels in either epithelial or whole uterus extracts, it did attenuate the
      estrogen-induced increase in c-fos mRNA by 50% in whole uterus extracts and by
      23% in epithelial extracts. The estrogen-induced increase in epithelial jun-B
      mRNA was not affected by progesterone pretreatment. Thus, in the immature rat
      uterus, no simple correlation exists between cellular proliferation and increased
      expression of the genes studied. However, progesterone completely blocked the
      repressive effect of estrogen on epithelial c-jun, suggesting a link between
      decreased c-jun expression and induction of cell proliferation in the uterine
      luminal epithelium. Estrogen repression of epithelial c-jun expression was
      hormone specific and sensitive to antiestrogen blockade. After estrogen
      treatment, epithelial c-jun mRNA decreased with a rate similar to its half-life,
      as determined in primary cultures of rat uterine cells. These results suggest
      that estrogen, acting through its receptor, directly represses transcription of c
      jun in the uterine epithelium. Differences in hormonal regulation of immediate
      early genes between epithelial and nonepithelial uterine tissues probably results
      from tissue-specific transactivating factors that control the expression of these
      genes.

PMID- 8137749
TI  - Estrogen differentially affects c-jun expression in uterine tissue compartments.
AB  - Estrogen rapidly induces expression of the jun immediate early gene family in
      mature and immature rodent uteri, suggesting that these protooncogenes are
      directly involved in the proliferative response of the uterus to estrogen. The
      jun family mRNAs, however, have not been localized to specific uterine cell
      types. Furthermore, it is necessary to differentiate between the response of the
      immature vs. the mature rat uterus to 17 beta-estradiol (E2-17 beta), because in
      the former, all uterine cell types respond to estrogen with increased DNA
      synthesis, but in the latter, the proliferative response is restricted to the
      uterine epithelial cells. In the present study, in situ hybridization was used to
      determine the cell type-specific location of mRNA encoding the immediate early
      genes c-jun, jun-B, and jun-D after the administration of E2-17 beta to mature
      and immature rats. Estradiol stimulated jun-B and jun-D expression primarily in
      the uterine luminal and glandular epithelium. The pattern of c-jun expression,
      however, was strikingly different; E2-17 beta repressed c-jun mRNA levels in the
      uterine luminal epithelium and simultaneously increased c-jun expression in the
      uterine myometrium. In mature vs. immature uteri, the general cell type-specific
      patterns of jun-B and jun-D expression were similar after estrogen
      administration. The expression of c-jun was increased by estrogen in the uterine
      glands as well the uterine myometrium of immature rats; however, in mature rats,
      uterine glandular epithelial cells did not respond to E2-17 beta administration
      with increased c-jun expression. These experiments demonstrate for the first time
      positive and negative regulatory actions of estrogen on c-jun expression and
      suggest a role for tissue-specific factors in the control of c-jun expression.
      The lack of maturational effects on jun gene expression implies that the
      differential response of the immature vs. the mature uterus to estrogen, in terms
      of cell proliferation, involves a point of control other than that at the level
      of the jun protooncogene family.

PMID- 8137750
TI  - The frog gonadotropin-releasing hormone-I (GnRH-I) gene has a mammalian-like
      expression pattern and conserved domains in GnRH-associated peptide, but brain
      onset is delayed until metamorphosis.
AB  - Recent evidence indicates a localized origin in the olfactory placode for the
      mammalian forebrain neurons that express GnRH. To identify the cellular and
      molecular signals that induce the GnRH phenotype, we cloned and characterized a
      cDNA encoding the GnRH prohormone, the precursor for both GnRH-I and GnRH
      associated peptide in the frog, Xenopus laevis, an embryonic model accessible to
      experimental manipulation. The 396-base cDNA represented a single mRNA species
      encoding an 89-amino acid prepro-GnRH that, unlike a recently cloned fish GnRH
      gene, was identical to both the mammalian GnRH decapeptide as well as multiple
      domains within GnRH-associated peptide. Serial section in situ hybridization
      histochemistry and immunocytochemistry in adult frog localized a forebrain system
      comprising 250-350 cell bodies whose overall neuroanatomy, including fiber
      projections, was very similar to that described for mammals. However, neither
      Northern nor in situ hybridization detected GnRH expression in midbrain, arguing
      that another frog gene encodes the midbrain GnRH-II expression pattern described
      by many others using antisera directed against the fish GnRH-I or chicken GnRH-II
      decapeptides. In contrast to mammals and birds, in which GnRH-expressing cells
      migrate into embryonic forebrain, frog GnRH cells were first detected after they
      reached their final position in the preoptic area during the late larval period.
      Thus, although previous studies proposed a complex organization for the GnRH
      system in the frog, our findings show that similar to mammals, there is a single
      gene that can account for the continuum of GnRH-I cells spanning frog forebrain.
      However, unlike mammals, in frogs, for unknown reasons, GnRH-I gene expression is
      suppressed until metamorphic climax.

PMID- 8137751
TI  - Gonadal hormones and gonadotropin-releasing hormone (GnRH) alter messenger
      ribonucleic acid levels for GnRH receptors in sheep.
AB  - GnRH regulates the synthesis and secretion of pituitary gonadotropins. The number
      of receptors for GnRH (GnRH-rec) can vary from 500 to 15,000-20,000/gonadotrope
      in ovine pituitary cultures after treatment with physiologically relevant
      combinations of gonadal hormones. This large range suggests that regulation of
      GnRH-rec expression may be an important control point in GnRH action at the
      pituitary level. Reported here are the changes in GnRH-rec mRNA associated with
      pituitary treatments (48 h) of 17 beta-estradiol (E), progesterone (P), and an
      enriched preparation of porcine follicular inhibin (IN). Northern blot analysis
      was used to detect 3 species of GnRH-rec mRNA in primary ovine pituitary culture
      [5.5 kilobases (kb; 32%), 3.6 kb (51%), and 1.4 kb (17%)]; all were changed in
      parallel by E, P, and IN. GnRH-rec mRNAs were increased 190% over control levels
      after treatment with either E or IN, and 400% with E and IN combined; when E and
      IN were added along with P, the increase was only 50% (P caused an 87% inhibition
      of E plus IN induction). The addition of P in the absence of any other treatment
      reduced levels of GnRH-rec mRNA by 50%. Studies were also conducted with GnRH
      agonists (GnRH-A) due to their widespread clinical use for down-regulating
      reproductive function in men and women. The addition of GnRH-A to cultures was as
      effective as P in blocking E plus IN induction of GnRH-rec mRNA. In vivo studies
      in wethers showed that 7 days of chronic treatment with GnRH-A decreased all
      sizes of ovine GnRH-rec mRNA by 84-89%. These data indicate that E, P, and IN
      change GnRH-rec levels at least in part by changing levels of GnRH-rec mRNAs.
      They also show that GnRH-A can almost entirely block E plus IN induction of GnRH
      rec mRNA in vitro and decrease levels of GnRH-rec mRNA in vivo in wethers.

PMID- 8137752
TI  - Role of protein kinase-A in homologous down-regulation of parathyroid hormone
      (PTH)/PTH-related peptide receptor messenger ribonucleic acid in human osteoblast
      like SaOS-2 cells.
AB  - Homologous down-regulation of PTH/PTH-related peptide (PTHrP) receptor expression
      occurs in several PTH-responsive osteoblastic cell lines, but the mechanisms
      responsible are not well understood. We have used wild-type SaOS-2 human
      osteoblastic cells, in which homologous PTH/PTHrP receptor down-regulation occurs
      within 4 h, and a mutant cAMP-resistant subclone (Ca4A strain), to investigate
      the mechanisms by which PTH/PTHrP receptor mRNA is regulated. SaOS-2 cells
      expressed a single 2.2- to 2.5-kilobase transcript of PTH/PTHrP receptor mRNA, as
      assessed by Northern blot analysis of total RNA with a cDNA probe encoding the
      human PTH/PTHrP receptor. Homologous down-regulation of this PTH/PTHrP receptor
      mRNA first became significant when SaOS-2 cells had been treated with human (h)
      PTH-(1-34) (10(-7) M) for 8-12 h. By 24 h, steady state levels of PTH/PTHrP
      receptor mRNA were reduced by about 50%. This effect was mimicked by both
      (Bu)2cAMP (DBcAMP; 0.5 mM) and forskolin (Fsk; 10(-5) M). In contrast, down
      regulation of PTH/PTHrP receptor mRNA by hPTH-(1-34), DBcAMP or Fsk was almost
      completely blocked in cAMP-resistant Ca4A cells. Short term (4-6 h) treatment
      with hPTH-(1-34), DBcAMP, or Fsk did not reduce steady state levels of PTH/PTHrP
      receptor mRNA in either SaOS-2 or Ca4A cells, although down-regulation was
      induced by 4-6 h of treatment with active phorbol esters such as 12-O
      tetradecanoyl phorbol-13-acetate (200 nM) or phorbol-12,13-didecanoate (200 nM).
      Neither thapsigargin (1 microM) nor ionomycin (200 nM), both of which stimulate
      calcium transients in these cells, altered PTH/PTHrP receptor mRNA expression.
      Treatment with hPTH-(39-84) and hPTH-(53-84), which do not activate either cAMP
      dependent protein kinase or protein kinase-C, but do stimulate 45Ca2+ uptake in
      these cells, did not alter PTH/PTHrP receptor mRNA expression. In the presence of
      actinomycin-D (1 microgram/ml), down-regulation of PTH/PTHrP receptor mRNA by
      hPTH-(1-34) was not observed. Cycloheximide (10 micrograms/ml) did not block down
      regulation of PTH/PTHrP receptor mRNA induced by hPTH-(1-34). We conclude that
      homologous down-regulation of PTH/PTHrP receptor mRNA in SaOS-2 cells occurs
      later than the decline in functional surface receptors via a mechanism that does
      not involve enhanced mRNA degradation or new protein synthesis, but is dependent
      upon cAMP/cAMP-dependent protein kinase.

PMID- 8137753
TI  - Synthesis and processing in vivo of the novel mouse thyrotropin beta-presubunit
      that contains an NH2-terminal extension sequence.
AB  - Expression of the single mouse TSH beta gene gives rise to multiple mRNAs, and we
      have previously shown that in vitro, one of these mRNAs gives rise to a novel TSH
      beta-presubunit due to initiation of translation at an in-frame start site unique
      to this mRNA which is up-stream of the normal start site. The novel presubunit
      contains a 17-amino acid NH2-terminal extension sequence compared to the normal
      presubunit. Although this extension sequence does not have the characteristics of
      a normal signal sequence, the novel TSH beta-presubunit was processed in vitro by
      microsomal membranes. In this study we have examined the translation product of
      this mRNA in intact cells and whether in vivo it gives rise to a processed
      secreted TSH beta-subunit that has an NH2-terminal sequence different from that
      of the established TSH beta-subunit. Firstly, mRNAs encoding alpha-presubunit and
      either the normal or novel TSH beta-presubunit were microinjected into Xenopus
      oocytes, and it was found that immunoprecipitable TSH dimer was secreted into the
      medium regardless of the mRNA used for TSH beta-subunit synthesis. However, less
      TSH was obtained when the TSH beta-subunit was derived from the extended TSH beta
      presubunit. Secondly, when COS cells were transiently transfected with plasmids
      expressing alpha-presubunit and either the normal or novel TSH beta-presubunit,
      secreted TSH was obtained when the TSH beta-subunit was derived from either
      presubunit. TSH dimer was also obtained when the TSH beta-presubunit was derived
      from a mRNA encoding the extended presubunit in which the down-stream AUG had
      been eliminated by site-specific mutagenesis. This demonstrated that the up
      stream translation start site was used in the intact cell and that secreted TSH
      beta-subunit was derived from the extended presubunit and not from normal
      presubunit resulting from translational readthrough to the down-stream AUG. When
      secreted TSH beta-subunits derived from the normal and extended TSH beta
      presubunits were digested with endoproteinase LysC, the NH2-terminal fragments
      were similar in size, suggesting that the NH2-terminal extension had little if
      any effect on the site of cleavage by signal peptidase. Our data, therefore,
      demonstrate that the longer TSH beta-presubunit is synthesized in vivo and
      strongly suggest that it is processed in the intact cell to give a mature
      secreted TSH beta-subunit indistinguishable from that derived from the normal TSH
      beta-presubunit.

PMID- 8137754
TI  - Decreased responsiveness of basal gluconeogenesis to insulin action in
      hepatocytes isolated from genetically obese (fa/fa) Zucker rats.
AB  - In vivo studies have demonstrated that hepatic glucose production is poorly
      responsive to insulin in genetically obese Zucker rats. In this work, we have
      investigated the modulation by insulin of basal gluconeogenesis, fructose 2,6
      bisphosphate levels, and pyruvate kinase and 6-phosphofructo 2-kinase activities
      in hepatocytes isolated from fed obese (fa/fa) or lean (Fa/-) rats.
      Gluconeogenesis was estimated by the conversion of a mixture of [14C]lactate
      pyruvate to [14C]glucose. Basal gluconeogenesis was significantly reduced in
      hepatocytes isolated from obese rats compared to that measured in hepatocytes
      from lean animals (0.63 +/- 0.09 vs. 1.47 +/- 0.05 mumol lactate converted to
      glucose/g cells.20 min; n = 3-4; P < 0.001). In hepatocytes isolated from lean
      rats, insulin, without affecting the cellular cAMP concentration, caused a dose
      dependent inhibition of the rate of gluconeogenesis, which was accompanied by a
      significant increase in fructose 2,6-bisphosphate levels and activation of both
      pyruvate kinase and 6-phosphofructo 2-kinase. In contrast, in hepatocytes
      isolated from obese (fa/fa) rats, neither basal gluconeogenesis nor any of the
      other metabolic parameters mentioned were significantly modified by insulin, even
      when assayed at high hormonal concentrations (10 nM). These results demonstrate a
      lack of responsiveness of hepatic gluconeogenesis to short term insulin action in
      genetically obese (fa/fa) rats.

PMID- 8137755
TI  - Control of posterior pituitary vasopressin content: implications for the
      regulation of the vasopressin gene.
AB  - Axon terminals in the posterior pituitary store large quantities of the hormone
      vasopressin (AVP), buffering the synthesizing neurons in the hypothalamus against
      acute changes in physiological demand for hormone release. The dynamics of
      pituitary AVP content reflect the competing processes of release and synthesis.
      This report demonstrates substantial increases in pituitary AVP content in the
      maturing rat. Between 7-10 weeks of age, the total pituitary AVP content in the
      rat increases from 957 +/- 72 to 1667 +/- 160 ng. Cross-sectional data indicate a
      parallel relationship between body weight and pituitary AVP content.
      Nevertheless, weight maintenance does not affect age-related increases in AVP
      content. Decreasing demand for hormone release and synthesis by inducing
      hyponatremia blocks subsequent pituitary accumulation. After withdrawing the
      hyponatremic experimental conditions, animals resume accumulation of pituitary
      AVP, but do not catch up to age-matched controls. This indicates that increases
      in pituitary AVP content do not result from a feedback signal from the neural
      lobe, but rather, pituitary AVP levels passively reflect changes in hormone
      release and compensatory synthesis.

PMID- 8137756
TI  - The pharmacokinetics, tissue localization, and metabolic processing of
      recombinant human hepatocyte growth factor after intravenous administration in
      rats.
AB  - Hepatocyte growth factor (HGF) is a pluripotent mitogen thought to be involved in
      liver regeneration. It is synthesized as a single chain promitogen and requires
      proteolytic processing to a two-chain heterodimeric form for biological activity.
      The pharmacokinetics and tissue distribution of radioiodinated single chain
      recombinant human HGF ([125I]rhuHGF) were studied in male Sprague-Dawley rats
      after an iv bolus dose. Pharmacokinetic parameters were determined from
      trichloroacetic acid-precipitable radioactivity in serum samples. There was a
      rapid distribution phase (t1/2 alpha = 3.1 min) and a slower elimination phase
      (t1/2 beta = 114 min). Tissue distribution was assessed by whole body
      autoradiography 5, 60, and 1440 min after an iv bolus dose. rhuHGF rapidly
      distributed to the liver, kidney, adrenal gland, and spleen. The importance of
      the liver in the rapid clearance and subsequent conversion of single chain pro
      rhuHGF to the mitogenically active two-chain form was demonstrated using an
      isolated rat liver perfusion system. TCA-precipitable radioactivity excreted into
      the bile (1.0 +/- 0.1%) and released into the venous effluent (38.9 +/- 6.1%) was
      monitored for 60 min after a portal vein injection. The appearance of
      radioactivity in both the bile and venous effluent was maximal between 20-35 min.
      Further characterization of the reduced samples by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and autoradiography revealed that the two
      chain form of [125I]rhuHGF was the predominant form after hepatic perfusion.
      These studies suggest that the liver plays a major role in the rapid clearance
      and subsequent activation of pro-rhuHGF in vivo.

PMID- 8137757
TI  - Thyroid hormone receptor binds with unique properties to response elements that
      contain hexamer domains in an inverted palindrome arrangement.
AB  - Thyroid hormone receptor (T3R)-accessory protein heterodimers preferentially bind
      to thyroid hormone response elements (TREs), which contain hexamer domains
      arranged as a direct repeat separated by a 4-basepair gap (DR + 4). T3R
      homodimers, however, preferentially bind to elements that consist of an inverted
      palindrome. We now report on unique T3R binding patterns and functional
      characteristics of two such elements that mediate T3 regulation. We performed
      mutational analysis of the chicken lysozyme silencer F2 (LysF2) TRE and
      demonstrated that the two functional binding domains are arranged as an inverted
      palindrome separated by 6 basepairs. Both the LysF2 TRE and the similarly
      arranged myelin basic protein TRE bind T3R dimers at very low T3R concentrations.
      Despite the high relative affinity for T3R dimer binding, the T3 induction
      conferred by these elements is low compared to that of previously characterized
      TREs with a DR + 4 arrangement. The laminin-B1 gene element, previously shown to
      bind retinoic acid receptor, contains at least four hexameric binding domains.
      All of the domains can bind T3R simultaneously and are involved in conferring T3
      induction, but bind with a different pattern than that reported for retinoic acid
      receptor. T3R homodimer binding to a series of mutant laminin-B1 elements and T3
      induction were significantly correlated (r = 0.82; P < 0.05). T3R homodimer
      binding to LysF2 element mutants was not correlated with T3 induction (r = 0.32;
      P > 0.05); however, T3R-nuclear protein heterodimer binding was significantly
      correlated (r = 0.67; P < 0.05). T3R-nuclear protein heterodimers, but not
      homodimers, bound consistently to mutations of the LysF2 element that altered the
      gap between hexamers. The overall discordance between strong T3R binding to these
      elements and weak T3 induction indicates that the unusual hexamer arrangement
      places the T3R complex in an unfavorable configuration for maximal T3-dependent
      transactivation. The differential T3 sensitivity of generalized resistance to
      thyroid hormone-associated T3R mutants to the LysF2 element compared with the DR
      + 4 arrangement suggests that these unique features may have physiological
      significance.

PMID- 8137758
TI  - Carboxyl-terminal parathyroid hormone fragments stimulate osteoclast-like cell
      formation and osteoclastic activity.
AB  - The controversy still exists about the biological activity of carboxyl (C)
      terminal PTH fragments. The present study was performed to examine the effect of
      C-terminal PTH fragments on osteoclast-like cell formation and bone-resorbing
      activity. In contrast to human (h) PTH-(1-34) or hPTH-(1-84), any C-terminal
      fragments examined [hPTH-(35-84), hPTH-(53-84), and hPTH-(69-84)] did not affect
      cellular cAMP production and intracellular calcium in osteoblastic UMR-106 cells.
      Although hPTH-(1-84) caused an increase in cAMP production and intracellular
      calcium less effectively than hPTH-(1-34) in UMR-106 cells, the former caused a
      stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone
      cell cultures more effectively than the latter. All of the C-terminal fragments
      significantly stimulated osteoclast-like cell formation, and their effectiveness
      seemed to depend on the amino acid length of the fragments. The conditioned
      medium from UMR-106 cells pretreated with C-terminal PTH as well as amino
      terminal PTH significantly stimulated osteoclast-like cell formation from mouse
      hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating
      factor. Moreover, all of the C-terminal fragments stimulated osteoclast-like cell
      formation from hemopoietic blast cells even in the absence of osteoblasts, and
      their effectiveness seemed to depend on the length of fragments. As for bone
      resorbing activity by mature osteoclasts, all of the C-terminal fragments
      stimulated bone resorption in osteoblast-containing mouse bone cell cultures,
      whereas these fragments did not affect the bone-resorbing activity of isolated
      rabbit osteoclasts. The present study first indicates that C-terminal PTH
      fragments stimulate osteoclast-like cell formation as well as bone-resorbing
      activity by mature osteoclasts in the presence of osteoblasts and accelerate
      osteoclast-like cell formation from hemopoietic blast cells in the absence of
      osteoblasts.

PMID- 8137759
TI  - Cellular basis for follicle-stimulating hormone-stimulated calcium signaling in
      single rat Sertoli cells: possible dissociation from effects of adenosine 3',5'
      monophosphate.
AB  - To study the cellular basis for FSH-stimulated dose-dependent graded increases in
      intracellular Ca2+ concentrations in populations of Sertoli cells, we
      investigated the effects of FSH on free Ca2+ ion concentrations ([Ca2+]i) in
      individual rat Sertoli cells using the Ca(2+)-sensitive dye fura-2/AM and digital
      fluorescent videomicroscopy. Ovine or rat FSH elicited a hormone-specific rise in
      [Ca2+]i within 20-140 sec, with a peak level 2.7 +/- 0.9-fold greater than the
      basal value (mean +/- SEM; n = 8) lasting for 4-16 min. The amplitude and
      kinetics of the FSH-induced [Ca2+]i signal were not dose dependent. Instead,
      increasing doses of FSH recruited a higher percentage of responding cells.
      Chelation of extracellular Ca2+ or cotreatment with verapamil or cobalt abolished
      FSH-induced [Ca2+]i increases. Furthermore, in the presence of extracellular
      Mn2+, direct evidence for FSH-mediated Ca2+ influx was obtained from the quench
      of fura-2 fluorescence. Induced Ca2+ increases were mimicked by forskolin or
      protein kinase-A type I activators [8-(6-amino-hexyl)amino-cAMP and N6-benzoyl
      cAMP (N6B)]. However, the cAMP analogs, 8-bromo-cAMP, N6,2'-O-dibutyryl cAMP, or
      protein kinase-A type II activators (8-thiomethyl-cAMP and N6B), induced [Ca2+]i
      increases even in the absence of extracellular Ca2+, and the time course of the
      [Ca2+]i rise induced by cAMP analogs was more rapid than that induced by FSH.
      Similarly, the uninhibited rise in [Ca2+]i induced by FSH in pertussis toxin
      pretreated Sertoli cells suggests that PT-sensitive G-proteins are not involved
      in the action of FSH on [Ca2+]i. In summary, we demonstrate that FSH evokes
      sustained [Ca2+]i increases in single Sertoli cells in a nongraded fashion and
      recruits increasing numbers of responding cells in a dose-dependent fashion. We
      also provide explicit evidence that FSH induces Ca2+ influx. Mimicry of the FSH
      induced [Ca2+]i rise by certain cAMP analogs [8-(6-amino-hexyl)amino-cAMP and
      N6B; protein kinase-A type I activator] or forskolin suggests that Ca2+ may be
      part of a dual pathway of cAMP-initiated intracellular signaling.

PMID- 8137760
TI  - Characterization of the 2-deoxyglucose effect on the adrenocortical axis.
AB  - In the present study we examined the mechanisms involved in the activation of the
      hypothalamo-pituitary-adrenal (HPA) axis after administration of the glucose
      analog 2-deoxyglucose (2-DG), which inhibits intracellular glucose use. Adult
      male rats were injected with either 2-DG (400 mg/kg body wt ip) or vehicle and
      were killed 60 min later. 2-DG increased serum ACTH and corticosterone (CS) by 3-
      and 7-fold, respectively, as compared to vehicle-treated rats. Bilateral lesions
      of the lateral hypothalamic area completely inhibited the 2-DG-induced HPA axis
      activation. Administration of 2-DG caused a significant depletion in the CRF-41
      content of the median eminence (ME). Pretreatment with dexamethasone (80
      micrograms/kg body wt ip) inhibited the 2-DG-induced depletion of ME CRF-41 and
      the increase in serum ACTH and CS. To investigate the role of type I and type II
      corticosteroid receptors in mediating the feedback effect of endogenous
      glucocorticoids on the responses to 2-DG, specific type I (RU-28318) or type II
      (RU-38486) receptor antagonists were injected intracerebroventricularly (icv) (1
      microgram/kg body wt). In rats pretreated with these antagonists, the recovery of
      serum ACTH and CS to basal levels after 2-DG was markedly inhibited. Injection of
      the serotonin (5-HT) neurotoxin, 5,7-dihydroxy-tryptamine, either into the raphe
      nuclei or icv, which caused a 50 and 70% depletion of the hypothalamic 5-HT
      content, respectively, did not affect the HPA axis responses to 2-DG. In
      contrast, icv injection of ketanserin, a 5-HT2 receptor antagonist, completely
      inhibited the 2-DG-induced activation of the HPA axis. The results suggest that:
      1) the lateral hypothalamic area is involved in the mediation of the HPA axis
      responses to 2-DG; 2) CRF-41 released from the ME plays a dynamic role in
      mediating the 2-DG-induced adrenocortical response; 3) the effect of 2-DG is
      sensitive to inhibition by dexamethasone, and the feedback effect exerted by
      endogenous glucocorticoids is mediated by both type I and type II corticosteroid
      receptors; and 4) 5-HT is involved in the activation of the HPA axis after 2-DG
      via its interactions with 5-HT2 receptors.

PMID- 8137761
TI  - Granulocyte-macrophage colony-stimulating factor corrects macrophage
      deficiencies, but not osteopetrosis, in the colony-stimulating factor-1-deficient
      op/op mouse.
AB  - The op mutation in the mouse is in the coding region of the colony-stimulating
      factor-1 (CSF-1) gene, prevents formation of biologically active factor, and,
      thus, results in generalized macrophage deficiency and, in osteopetrosis,
      secondary to deficiency of osteoclasts. Although a few macrophages and
      osteoclasts are present in these mutants, it was not clear whether the inability
      of endogenous granulocyte-macrophage CSF (GM-CSF) to compensate for the absence
      of CSF-1 was due to the limitations of biological activity of this molecule or to
      its inability to reach respective target populations. In this study, we examined
      whether sc GM-CSF in large doses (20-40 micrograms/mouse.day) for 3 weeks would
      correct some or all of the deficiencies observed in mutant mice. All organ
      macrophage populations tested (liver, spleen, thymus, marrow, pleural, and
      peritoneal cavity) were significantly increased, reaching levels exceeding those
      observed in normal mice. Restoration of peritoneal and pleural macrophage
      populations by sc GM-CSF is of particular interest, because it was not previously
      observed in op/op mice treated with sc CSF-1. In contrast, there was no
      indication of increased bone resorption, no appearance of osteoclasts, and no
      tooth eruption in response to GM-CSF treatment. These data suggest that GM-CSF is
      able to compensate for the absence of CSF-1 during macrophage formation, but is
      unable to play a similar role in osteoclast differentiation.

PMID- 8137762
TI  - Expression of parathyroid hormone-related peptide in relation to perturbations of
      gastric motility in the rat.
AB  - We studied the expression of PTH-related peptide (PTHrP) and its mRNA in rat
      gastric smooth muscle in relation to various gastric motility states. Male rats
      were divided into groups subjected to fasting, feeding ad libitum, cold restraint
      stress, pyloric ligation, and carbachol stimulation. Cold restraint stress
      induced abnormal contractions. Rhythmic and moderate contractions were produced
      by carbachol administration, and marked distension was induced by pyloric
      ligation. PTHrP mRNA expression was weak in the physiological fasting and feeding
      states, but was markedly increased by pyloric ligation and carbachol stimulation.
      PTHrP and its mRNA were localized to the proper muscle layer and muscularis
      mucosa, but not in the mucosa by immunohistochemistry and in situ hybridization.
      The gene expression of PTHrP receptor in the gastric tissue was confirmed by
      reverse transcription-polymerase chain reaction, but serum PTHrP levels did not
      increase in all groups. These findings suggest that PTHrP acts as an autocrine or
      paracrine factor in gastric smooth muscle that responds to muscle activity caused
      by distension and cholinergic stimulation. However, PTHrP gene expression was
      decreased by stress despite the presence of strong contractions, and the
      sufficient relaxation did not occur. PTHrP suppression by stress is caused by the
      increase in corticosterone, as pretreatment of metyrapone, an inhibitor of 11
      beta-hydroxylation, enhanced PTHrP gene expression in association with serum
      corticosterone suppression. In conclusion, PTHrP might be an important
      gastrointestinal peptide that regulates gastric contractile activity and is
      influenced by the serum corticosterone level.

PMID- 8137763
TI  - Cytochemical detection of gonadotropin-releasing hormone-binding sites on rat
      pituitary cells with luteinizing hormone, follicle-stimulating hormone, and
      growth hormone antigens during diestrous up-regulation.
AB  - Pituitary cells with GnRH receptors increase over 2-fold during diestrus to reach
      a peak during the morning of proestrus. This is followed by a rapid fall during
      the afternoon of proestrus to reach a nadir by estrus. The objective of this
      study was to learn the identity of the new target cells added during diestrus.
      This was particularly important in view of recent evidence showing that
      gonadotropes with LH beta and FSH beta mRNA have GH antigens. Pituitary cells
      from diestrous and proestrous rats were exposed to biotinylated GnRH (Bio-GnRH)
      for 10 min. Bio-GnRH was detected by avidin peroxidase, and then the cells were
      immunolabeled for pituitary hormones. The percentages of cells labeled for Bio
      GnRH rose during diestrus from 6.6 +/- 0.8% in the morning to 11.9 +/- 0.7% by
      evening (mean +/- SD). By the morning of proestrus, the percentages of Bio-GnRH
      target cells increased further to 16 +/- 0.7%. The percentages of pituitary cells
      dual labeled for LH beta antigens and Bio-GnRH rose from 4.3 +/- 0.6% to 9% +/-
      1% during diestrus and averaged 13 +/- 0.7% by the morning of proestrus. At this
      time, 90% of cells with LH antigens bound Bio-GnRH. When percentages of pituitary
      cells with FSH beta antigens and Bio-GnRH-binding sites were analyzed, there was
      an increase during diestrus from 4 +/- 0.4% to 9.7 +/- 0.7%; a peak level of 14
      +/- 0.9% was reached by the morning of proestrus. Bio-GnRH binding was expressed
      by 86% of FSH cells during this peak. Finally, GH antigens were also detected in
      GnRH target cells. The percentage of cells dual labeled for Bio-GnRH and GH
      increased from 4 +/- 0.8% to 8 +/- 1% during diestrus and the morning of
      proestrus. During the diestrous and proestrous peak periods of expression, Bio
      GnRH binding was seen in 32% of GH cells. None of the other pituitary cell types
      showed significant GnRH binding. These studies showed that most of the new GnRH
      receptive cells stem from maturing gonadotropes. Half of the GnRH-receptive cells
      also contain GH antigens, which correlated with results from previous studies
      that showed GH antigens in cells with gonadotropin mRNAs. This might reflect
      expression of gonadotrope functions by a subset of GH cells. Alternatively, the
      GH antigens may be bound to GH receptors in gonadotropes. This latter possibility
      may signify a paracrine regulation of gonadotrope function by GH.

PMID- 8137764
TI  - Follistatin decreases activin-stimulated FSH secretion with no effect on GnRH
      stimulated FSH secretion in prepubertal male monkeys.
AB  - Follistatin is an activin-binding glycoprotein that decreases FSH secretion in
      vitro and in vivo in rats. The mechanism by which follistatin acts is unclear,
      but it has been suggested that it may bind endogenous activin and neutralize its
      effects. In this study, we wished to test the ability of follistatin to suppress
      FSH secretion in vivo in primates whose FSH secretion has been stimulated by
      activin or by GnRH. Six prepubertal male monkeys were injected intravenously with
      human recombinant follistatin at the dose of 90 micrograms/kg or 180
      micrograms/kg plus activin (90 micrograms/kg) or GnRH (10 micrograms/kg).
      Frequent blood samples were drawn for 12 hours following each injection. Bio FSH
      and LH levels were measured in those samples. GnRH and activin each stimulated
      FSH bioactivity. Both doses of follistatin significantly inhibited the activin
      induced increase in FSH (p < 0.05). The GnRH-induced increase in FSH was not
      affected by follistatin. LH levels were not affected by follistatin in any of the
      studies. These data suggest that follistatin can suppress the activin-induced
      increase in FSH in primates and is consistent with the hypothesis that
      follistatin can block the physiological effects of endogenous activin in
      primates. This effect is likely to be due to the binding of follistatin to
      activin either in the peripheral circulation or at the pituitary level.

PMID- 8137765
TI  - Steroid hormones modulate the production of nitric oxide and cGMP in the rat
      uterus.
AB  - Previously, we demonstrated the presence of an L-arginine-nitric oxide (NO)
      cyclic guanosine monophosphate (cGMP) pathway in the rat uterus and that NO
      inhibits contractility during pregnancy but not during delivery. In the present
      study, we investigated the possible role of sex steroid hormones in the
      regulation of NO synthesis and cGMP generation. NO, measured as nitrite
      production, and cGMP were determined in full thickness uterine tissues from
      either pregnant rats on different gestational days or nonpregnant animals after
      treatment with steroid hormones. NO formation was low in tissues from nonpregnant
      rats, substantially increased during pregnancy and decreased during labor and
      immediately postpartum. The cGMP content in the same tissues followed a similar
      trend. Uterine nitrite production and cGMP levels from animals treated with
      estradiol and estradiol + progesterone were significantly lower compared to those
      treated with vehicle or progesterone. These data provide strong evidence that the
      NO-cGMP system is upregulated during pregnancy to maintain uterine quiescence and
      a rise in estrogen at term could inhibit this system and thus initiate labor.

PMID- 8137766
TI  - Effect of tyrosine kinase inhibitors on islets of Langerhans: evidence for
      tyrosine kinases in the regulation of insulin secretion.
AB  - In order to determine if tyrosine kinase activation is involved in the changes in
      islet function, the effect of tyrosine kinase inhibitors on insulin secretion and
      islet cell proliferation was examined in cultured islets of Langerhans. When
      islets were exposed to 100 microM genistein or 2 microM herbimycin A, large 5- to
      10-fold increases in insulin secretion were observed. The effect on insulin
      secretion was detected within 1 hr and was maintained for at least 4 days. The
      glucose sensitivity of islets exposed to genistein was dramatically increased as
      demonstrated by a shift of the glucose-dose response curve to lower glucose
      concentrations. In contrast, islet cell proliferation was dramatically reduced in
      the presence of these tyrosine kinase inhibitors in the absence or presence of
      PRL. These very large changes observed in islets suggest that tyrosine kinases
      may have important roles in the regulation of beta-cell function.

PMID- 8137767
TI  - Prolactin induces rapid p95/p70 tyrosine phosphorylation, and protein binding to
      GAS-like sites in the anx Icp35 and c-fos genes.
AB  - Several growth factors and cytokines have been proposed to act through signaling
      pathways related by their dependence on tyrosine phosphorylation of latent
      transcription factors, and their use of similar transcription factor binding
      sites. Related mechanisms have previously not been reported for prolactin, growth
      hormone, or any other glandular hormone. We have identified sequences in the
      annexin Icp35 gene that are related to regulatory sequences in mammary gland milk
      protein genes, and then used DNA binding assays to show that PRL induces
      transient expression of factors specific for these sequences. The sequences in
      question are partially related to the core homology of the interferon (IFN)gamma
      activated sequence (GAS). Considering that the prolactin-regulated factors might
      be related to the p91 component of IFN gamma-activated factor, we used
      immunoassays to show that prolactin induced tyrosine phosphorylation of a protein
      that comigrated with immunoreactive relatives of p91, and that antibody to p91
      specifically interfered with the prolactin-induced binding activity on the
      annexin Icp35 gene.

PMID- 8137768
TI  - Science and an EPA mission statement.

PMID- 8137769
TI  - A new soot standard?

PMID- 8137770
TI  - Guinea worm gone.

PMID- 8137771
TI  - Arsenic and new data.

PMID- 8137772
TI  - Brain food.

PMID- 8137773
TI  - Milwaukee's water woes.

PMID- 8137774
TI  - Fetal lead toxicity.

PMID- 8137776
TI  - No more muddy waters: cleaning up the Clean Water Act.

PMID- 8137775
TI  - In our own backyards: the continuing threat of hazardous waste.

PMID- 8137777
TI  - X-ray fluorescence analysis of lead in bone.

PMID- 8137778
TI  - Physiologically based toxicokinetic modeling of 1,3-butadiene lung metabolism in
      mice becomes more important at low doses.
AB  - This paper describes a physiologically based toxicokinetic model for 1,3
      butadiene uptake, distribution, and metabolic clearance in mice. Model parameters
      for metabolic activity were estimated from the correspondence between computer
      simulation studies and experimental results as published in the literature. The
      parameterized model was validated with independent literature data. With the
      resulting model, the relative importance of lung metabolism as compared to
      metabolism in the liver increased with decreasing ambient air concentrations.
      This was due to saturation of metabolism in the alveolar area of the lung, which
      occurred in the simulations at ambient air concentrations well below current
      threshold limit values. At higher air concentration, liver metabolism became
      relatively more important. The tendency toward increased importance of lung
      metabolism at low doses indicates the necessity of careful extrapolation of in
      vivo results to low doses. Moreover, this trend may also contribute to species
      difference in susceptibility to the carcinogenic activity of butadiene.

PMID- 8137779
TI  - Effects of pre- and postnatal exposure to chlorinated dioxins and furans on human
      neonatal thyroid hormone concentrations.
AB  - Animal studies have shown that dioxins influence plasma thyroid hormone
      concentrations. To investigate the effect of chlorinated dioxins and furans on
      thyroid hormone concentrations in humans, we studied 38 healthy breast-fed
      infants. The study population was divided into two groups according to the dioxin
      concentrations in milk fat of their mothers. Blood samples were taken at birth
      and at the ages of 1 and 11 weeks. At birth a tendency to higher total thyroxine
      (tT4) concentrations was found in the high exposure group. At the ages of 1 and
      11 weeks the increase of mean tT4 concentrations and tT4/thyroxine-binding
      globulin ratios in the high exposure group reached significance as compared to
      the low exposure group. At birth and 1 week after birth, mean thyrotropin (TSH)
      concentrations were similar in both groups, but at the age of 11 weeks the mean
      TSH concentrations were significantly higher in the high exposure group. We
      postulate that the observed plasma tT4 elevation in infants exposed to dioxins
      before and after birth is the result of an effect on the thyroid hormone
      regulatory system.

PMID- 8137780
TI  - Electrical and freeze-fracture analysis of the effects of ionic cadmium on cell
      membranes of human proximal tubule cells.
AB  - We previously reported that cell cultures of human proximal tubule (HPT) cells
      respond to ionic cadmium in a manner consistent with well-defined Cd(2+)-elicited
      responses reported for in vivo systems. However, one unique finding was that the
      transepithelial electrical resistance and tight junction sealing strands were
      altered as a result of Cd2+ exposure at micromolar concentrations. These
      alterations are reexamined in detail in the present report to determine whether
      the Cd(2+)-induced alterations are specific alterations in the tight junction
      structure or reflect a general alteration in the cell membrane. Exhaustive
      analysis of tight junction sealing strands demonstrated no significant
      alterations due to Cd2+ exposure, even at the concentration that elicited a
      significant reduction in transepithelial resistance. Further analysis of
      intramembrane particle distribution demonstrated a significant increase in apical
      intramembrane particles, indicating that Cd2+ exposure altered the
      characteristics of the apical cell membrane. Overall, the results were consistent
      with evidence of Cd(2+)-induced alteration in the apical cell membrane of the HPT
      cell.

PMID- 8137781
TI  - Air pollution and daily mortality in Erfurt, east Germany, 1980-1989.
AB  - In Erfurt, Germany, unfavorable geography and emissions from coal burning lead to
      very high ambient pollution (up to about 4000 micrograms/m3 SO2 in 1980-89). To
      assess possible health effects of these exposures, total daily mortality was
      obtained for this same period. A multivariate model was fitted, including
      corrections for long-term fluctuations, influenza epidemics, and meterology,
      before analyzing the effect of pollution. The best fit for pollution was obtained
      for log (SO2 daily mean) with a lag of 2 days. Daily mortality increased by 10%
      for an increase in SO2 from 23 to 929 micrograms/m3 (5% quantile to 95%
      quantile). A harvesting effect (fewer people die on a given day if more deaths
      occurred in the last 15 days) may modify this by +/- 2%. The effect for
      particulates (SP, 1988-89 only) was stronger than the effect of SO2. Log SP
      (daily mean) increasing from 15 micrograms/m3 to 331 micrograms/m3 (5% quantile
      to 95% quantile) was associated with a 22% increase in mortality. Depending on
      harvesting, the observable effect may lie between 14% and 27%. There is no
      indication of a threshold or synergism. The effects of air pollution are smaller
      than the effects of influenza epidemics and are of the same size as meterologic
      effects. The results for the lower end of the dose range are in agreement with
      linear models fitted in studies of moderate air pollution and episode studies.

PMID- 8137782
TI  - Protection against carbon tetrachloride-induced hepatotoxicity by pretreating
      rats with the hemisuccinate esters of tocopherol and cholesterol.
AB  - Previous studies have demonstrated that alpha-tocopheryl hemisuccinate (TS)
      protects hepatocyte suspensions from chemical-induced toxicity. It has been
      suggested that TS cytoprotection is related to unique properties of the TS
      molecule or is dependent on the cellular release and activity of unesterified
      alpha-tocopherol (T). To test the unique cytoprotective nature of TS in vivo, the
      protective ability of T and tocopherol esters against carbon tetrachloride (CCl4)
      induced hepatotoxicity in rats was examined. Hepatoprotection [determined by
      serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels
      and histopathology] was not observed after T (or tocopheryl acetate and
      tocopheryl nicotinate) administration, even though this treatment resulted in a
      fivefold elevation in hepatic T content. Only pretreatment with TS (100 mg/kg,
      intraperitoneally) resulted in partial hepatoprotection against CCl4 (2.9 g/kg,
      orally) toxicity. These findings suggest that hepatoprotection results not from
      the cellular accumulation of T but rather from the intact TS molecule. To test
      this hypothesis, the hepatoprotective capacity of cholesteryl hemisuccinate (CS),
      unesterified cholesterol, and cholesteryl acetate (CA) was examined against CCl4
      toxicity. As observed with the tocopherol derivatives, pretreatment with
      unesterified cholesterol or CA demonstrated no protective ability. However, when
      rats were pretreated with CS (100 mg/kg), the hepatotoxic effects of CCl4
      (elevated serum AST and ALT levels and centrilobular necrosis) were completely
      prevented. The prevention of CCl4-induced hepatotoxicity by CS and TS do not
      appear to result from an alteration in hepatic drug metabolism. These data
      clearly demonstrate that CS and TS are unique and powerful cytoprotective agents
      against CCl4 hepatotoxicity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137783
TI  - A short history of electrophoretic methods.
AB  - High resolution separation of proteins, based on charge differences, is possible
      with disc electrophoresis, displacement electrophoresis (isotachophoresis) and
      notably isoelectric focusing (IEF). Size separation is obtained in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The combination of gel
      IEF, followed by SDS-PAGE in a second-dimensional slab gel, i.e. two-dimensional
      gel electrophoresis, affords the highest resolution with up to several thousand
      spots per gel. Staining of proteins gives high resolution patterns which can be
      scanned and stored in comprehensive databases. Over the last 10 years the
      electrophoretic separation in gels and subsequent visualization of nucleic acids
      (DNA, RNA) and even genes as well as nucleotides have been much improved, making
      possible efficient mapping of the genes in humans and all other organisms. This
      has led to the biggest concerted endeavor in the history of science, i.e. the
      mapping of the human genome, which will be of importance as long as mankind
      exists. In the last years electrophoresis in capillaries has attracted much
      interest because for numerous substances, such as proteins nucleic acids,
      pharmaceuticals, metabolites, and peptides, it offers high resolution on the
      analytical scale with over 1 million theoretical plates. Electrophoretic methods
      have unprecedented impact on life sciences, providing a basis for unique advances
      in biochemistry, molecular biology, genetics, gene technology and medicine.

PMID- 8137784
TI  - How far have we progressed toward automated electrophoresis in sieving media of
      the twenty-first century?
AB  - The automation of electrophoresis in polymeric sieving media requires (i) an
      objective definition of the conditions (the polymer, its concentration, solvent,
      buffer, pH, ionic strength, temperature) under which a particular separation
      proceeds most effectively; (ii) apparatus capable of zone detection, acquisition
      by computer, evaluation (migration distance, zone width and area) and a print-out
      of the number of components, their size and net charge, and the polymer
      conditions under which each component separates most effectively from its two
      neighboring zones. Both of these prerequisites of automation have been met to a
      first approximation at this time and, after further maturation, assembly and
      streamlining should be able to fill the need of the coming century for a more
      efficient, nonarbitrary and cost-effective mode of macromolecular and cellular
      particle separation. (i) The realization of the qualitative equivalence of
      polymer solutions and gels has greatly increased our options in the choice of
      sieving media. That choice can be made objectively by correlating separation
      efficiency (S), particle size (R) and intrinsic viscosity (eta o) of the polymer.
      (S) is a function of the slope, KR(R), of the Ferguson plot [log(mobility) vs.
      polymer concentration], or with nonlinear plots (DNA, agarose) KR(R,T). KR is at
      present most easily derived from transverse pore gradient gels or by conducting
      capillary zone electrophoresis (CZE) at multiple polymer concentrations. Pore
      gradient CZE appears promising. CZE also defines the free mobility unequivocally.
      Computer programs exist to generate KR from migration distances (times), and
      optimal S and polymer concentration for a particular R from KR.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8137785
TI  - Electrophoretic light scattering.
AB  - Under a microscope, electrophoretic mobilities of visible particles can be
      determined in a free solution without any boundary or zonal separation.
      Electrophoretic light scattering based on the Doppler velocimetry can be taken as
      a nanometer-scale version of the above traditional electrophoresis. An
      electrophoretic light scattering apparatus was developed to enable mobility
      determination of proteins and surfactant micelles which have been outside the
      range of the electrophoresis.

PMID- 8137786
TI  - Our obsession with high resolution in gel electrophoresis: does it necessarily
      give the right answer?
AB  - Poor resolution of protein zones in an electrophoretic pattern may not
      necessarily be the result of poor technique. The example is given of the 'streak
      material', extracted from wheat flour, now recognised to be aggregated subunits
      of glutenin. The size distribution of the aggregated glutenin 'streak' is the key
      to elucidating the functional properties of wheaten dough. A stepped-layer gel
      technique has been devised to quantitate the proportions of aggregated glutenin
      in specific size groupings.

PMID- 8137787
TI  - Electrophoretic artifacts arising from the use of thiol-containing reagents.
AB  - Thiol reagents migrate as a curtain behind the salt front when loaded with the
      sample solution onto disc-electrophoresis gels. In immobilized pH gradients (IPG)
      the same compounds are driven by electrophoresis and electroosmosis from the
      alkaline to the neutral and acidic regions of the gradients. In either case, a
      dose-dependent sideways spreading results in spurious reduction between adjacent
      lanes if samples with and without reducing agent are loaded side by side.

PMID- 8137788
TI  - The variance and the quantity 2Dt in capillary zone electrophoresis.
AB  - The variance is generally used as a measure of dispersion of zones in capillary
      zone electrophoresis (CZE). It is a quantitative measure of the separation power
      of a system and different causes of dispersion can be rated by their partial
      variances, which can be summed up to total variance. However, the additivity is
      only valid for independent dispersion sources, a fact that often seems to be
      ignored. The ubiquitous dispersion source diffusion is taken into consideration
      by the Einstein term 2Dt. Other sources of dispersion are, e.g., injection,
      detection, thermal gradients, adsorption, and hydrodynamic flow. For each of
      these sources various variance expressions have been derived. The origin of the
      term 2Dt and its relation to the variance is explained and the calculation of
      variance in general is discussed. The equivalence of the diffusion variance and
      the term 2Dt is verified with some simple initial forms of sample zone and the
      additivity of variances in ideal zone electrophoresis is demonstrated. The change
      of conductivity in zones results in asymmetrical zone forms which is an
      indication of nonideality of a system. It is shown that in such cases the term
      2Dt is no longer valid and its use as an additive variance component leads to an
      erroneous total variance. Because in zone electrophoresis conductivity in a zone
      always changes more or less, the additivity of variances is never perfectly
      valid. However, in many cases the nonideality may be so small that the additivity
      in practice is still applicable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137789
TI  - On the use of dimensionless parameters in acid-base theory. V. Buffers composed
      of binary mixtures of monovalent weak acids and bases.
AB  - A general theory for buffers consisting of one weak acid and one weak base is
      developed, particular interest being devoted to the special case of doubly weak
      salts. The pH course as it varies with the acid/base concentration ratio is
      presented in equations and graphs. The influence of delta pK' = pK'b-pK'a, which
      can be negative as well as positive, is discussed and visualized in graphs. The
      buffer capacity is deduced as a function of pH. The buffer range is, at a
      maximum, 2.67 times that of a monovalent weak protolyte for delta pK' = 2.7 pH
      units. The buffer capacity curve has two maxima for delta pK' values bigger than
      0.77. For negative delta pK' values the buffer capacity curve has only one
      maximum, and the buffer range is not better than that of a monovalent protolyte.
      A general equation for the ionic concentrations is deduced, and as a corollary
      the degree of hydrolysis of the doubly weak salt is obtained as a function of
      delta pK'. For solutions of this salt, the relation between concentration and pH
      is elucidated by equations and graphs.

PMID- 8137790
TI  - Control of electrohydrodynamic distortion of sample streams in continuous flow
      electrophoresis using oscillating fields.
AB  - Continuous flow electrophoresis is a method to separate ions contained in a
      sample continuously injected into a laminar flow of electrolyte as a cylindrical
      stream. Usually, the sample is more conductive than the electrolyte, and the
      charges created at the sample-electrolyte interface lead to electrohydrodynamic
      distortions which reduce the separation power of this technique. We demonstrate
      theoretically that the rate of electrohydrodynamic distortion of a cylindrical
      sample stream can be reduced to zero, by superimposing to the AC field
      responsible for the separation of a DC field transverse to it and to the flow
      direction, with an appropriate frequency, and an effective strength equal to that
      of the DC field. Using a continuous flow electrophoresis chamber, in which such a
      field is produced using capacitive electrodes, the major predictions of the
      theory are confirmed. In particular, it is shown that a sample stream more
      conductive than the carrying electrolyte, which was seriously deformed in the
      absence of a transverse AC field, recovers its cylindrical shape in presence of
      the field. The implications of this discovery for the separating power of
      continuous-flow electrophoresis are discussed.

PMID- 8137791
TI  - Numerical simulation of protein separation by continuous-flow electrophoresis.
AB  - Continuous-flow electrophoresis is a process for separating protein mixtures on a
      preparative scale. Its resolution is determined by the migration distance at the
      collection plane and by the fineness of the filament occupied by each protein
      species. Filaments undergo spreading due to a number of different phenomena,
      among which electrokinetics and electrohydrodynamics are known to be important.
      In the first of these, differences in migration velocity between the ionic
      species give rise to local variations in pH and electrical conductivity near the
      protein filament. In the second, the local change in electrical conductivity
      distorts the electric field, thus inducing shear stress in the liquid and
      creating a local flow pattern. A numerical model has been developed to describe
      these phenomena when two proteins are being separated.

PMID- 8137792
TI  - Application of an improved density gradient electrophoresis apparatus to the
      separation of proteins, cells and subcellular organelles.
AB  - A DGE apparatus, made of Perspex, consisting of a separation column (5 x 2.2 cm)
      and containing a 0-4% linear Ficoll density gradient, was constructed. Only 2.5
      cm of the column were used for high resolution separations. A specially designed
      removable top cone permitted precise gradient introduction, thin sample layering
      (0.3-1 mm) and precise fractionation after electrophoresis. A bottom circular
      palladium anode (nongassing) was separated hydrodynamically but not electrically
      from the density gradient by a cation-permeable membrane. A top circular platinum
      cathode caused negatively charged particles to migrate upwards (levitation). Thin
      sample layering permitted short separation times (30-60 min) at only 3 V/cm (10
      mA). As for proteins, glycoforms of a1-antitrypsin were separated as well as
      isoenzymes of beta-hexoseaminidase. Furthermore, separation of transferrin (Tf)
      from the putative Tf-receptor complex was effectuated. The device was equally
      suitable for the separation of Megadalton proteins (mucins). Artificial mixtures
      of intact erythrocytes (rat, rabbit, human) were separated with high resolution.
      About 10(7) cells (of 100 microns3 cell volume) could be loaded onto the device.
      Crude microsomes from the human melanoma cell line Mel JuSo were separated after
      brief trypsin treatment within 38 min at 10 mA. Ratios of the migration
      velocities of the constituent organelles were: late endosomes (LE):lysosomes
      (L):Golgi (G):early endosomes (EE) = 1:0.94:0.77:0.55 and under slightly
      different conditions LE:L:G:endoplasmatic reticulum (ER):plasma membrane (PM) =
      1:0.87:0.64:0.58:0.49.

PMID- 8137793
TI  - Centrifuge-blotting of proteins after separation by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis.
AB  - A protein transfer method which allows elution and immobilization of polypeptides
      onto a polyvinylidene difluoride (PVDF) membrane has been developed. The protein
      band in a gel is eluted by centrifugation. The centrifuge-blotting procedure
      involves the following steps: (i) visualization of the protein in a sodium
      dodecyl sulfate (SDS)-polyacrylamide gel with 1 M KCl, (ii) excision of the
      protein band and equilibration for 15 min in a solution of 0.05% SDS/5%
      methanol/0.02% dithiothreitol in distilled water, (iii) placing the gel piece in
      direct contact with the PVDF membrane in the receptacle, (iv) centrifugation at
      3000 g for 1 h. A 10 kDa cut-off dialysis membrane is placed beneath the PVDF
      membrane to retain nonimmobilized protein. The N-terminal sequence of the
      immobilized protein on the PVDF membrane was determined. For proteins with a
      molecular mass less than 30 kDa, an overall yield between 10%-30% has been
      obtained.

PMID- 8137794
TI  - Isoelectric focusing in immobilized pH gradients of the glucose transporter from
      human red cell membranes.
AB  - Isoelectric focusing of the human red cell glucose transporter (a transmembrane
      protein) was performed in immobilized pH gradients. Isoelectric focusing of
      integral membrane proteins presents problems that are related to the amphiphilic
      nature of these proteins. Solubilizing additives must be used to counteract
      hydrophobic effects. In our case, urea and the nonionic detergent, Triton X-100,
      were used. Focusing was done at 15 degrees C. The isoelectric point (pI) of the
      glucose transporter (freshly purified by anion-exchange chromatography in the
      presence of octyl glucoside) was determined at 8.4 +/- 0.05 (n = 9), in good
      agreement with our earlier determinations by two-dimensional electrophoresis with
      isoelectric focusing in the presence of carrier ampholytes in the first
      dimension. The width of the focused zone was approximately 0.1 pH unit, more
      narrow than after focusing with carrier ampholytes. In an immobilized pH gradient
      from pH 7 to 10, the transporter region at pH 8.4 comprised one major and one or
      two minor zones. The pH interval 4-10 was also used and showed a single
      transporter zone. The glucose transporter tends to self-associate in detergent
      solution. Octyl glucoside-purified glucose transporter formed oligomers during
      incubation at 37 degrees C. Upon focusing, these oligomers appeared in a wide pH
      interval far below pH 8.4.

PMID- 8137795
TI  - Peculiarities in electrophoretic behavior of different serum albumins.
AB  - Behavior of serum albumins of different species was compared with regard to
      electrophoretic mobility under native conditions, molecular mass and isoelectric
      point in presence or absence of denaturing agents. In addition to serum samples
      from human, horse, cow, pig, cat, dog, sheep, goat, chicken, rabbit, mouse, and
      rat, commercially available standards or albumin preparations obtained by
      chromatographic procedures were analyzed. Feline and canine albumins showed
      marked differences in all investigated methods. Our experiments also revealed
      several factors influencing albumin patterns, especially during isoelectric
      focusing in immobilized pH gradients or in the presence of carrier ampholytes.

PMID- 8137796
TI  - Degradation of fibrinogen and fibrin by plasmin and nonplasmin proteases in the
      chronic subdural hematoma: evaluation by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and immunoblot.
AB  - To characterize local hyperfibrinolysis in the pathogenesis of chronic subdural
      hematoma (CSDH), fibrin degradation products (FDPs) were separated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to identify each
      FDP fragment (fragments HMW, YY, DY and DD) by immunoblotting. The
      electrophoretic patterns of FDP in 40 hematomas from 33 patients could be
      categorized into 3 patterns; (i) type 1, the sharp DY and DD bands; (ii) type 2,
      the broad DY and DD bands; and (iii) type 3, the sharp DY and DD with two bands
      with higher molecular weights than fragment DY and DD. The broadening of DY and
      DD bands was reproduced by incubating the sample containing sharp DD and DY bands
      with the hemolyzed peripheral blood cells. These results indicated that the
      hyperfibrinolysis in CSDH could be characterized by the constant and incomplete
      proteolysis of fibrinogen and fibrin by plasmin and further degradation of FDPs
      by non-plasmin proteases released from hemolyzed blood cells.

PMID- 8137797
TI  - Salivary protein interactions with oral bacteria: an electrophoretic study.
AB  - The relatively low levels of human salivary proteins in whole saliva as compared
      to the ductal secretions may be related to their interaction with oral bacteria.
      These interactions are thought to play an important role in the microbial
      colonisation of the mouth, and salivary proteins adsorbed to oral surfaces have
      been implicated in adherence. In this study we attempted to investigate the
      prevalence of interactive strains by screening a range of oral bacteria. Parotid
      saliva was incubated with bacterial suspensions and consequent alterations to the
      salivary protein profile determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). A number of salivary components were found to be
      preferentially removed, particularly by those species known to be primary
      colonizers of clean tooth surfaces.

PMID- 8137798
TI  - Electrophoretic analysis of stimulated cat parotid saliva.
AB  - The proteins of parasympathetically stimulated cat parotid saliva were analyzed
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and high
      resolution two-dimensional electrophoresis (2-DE). SDS-PAGE revealed up to 30
      polypeptide bands in microliter volumes of unconcentrated saliva. The patterns
      were highly reproducible and characterized by prominent bands of M(r) 57,000,
      M(r) 30,000 and M(r) 15,000. The major protein (M(r) 30,000) appeared as a dimer
      (M(r) 60,000) when electrophoresed under non-reducing conditions but dissociated
      into its monomeric form when the SDS concentration of the denatured samples was
      increased from 1 to 5%. This indicates a noncovalent association. The protein
      patterns of saliva from different cats differed slightly but sequential samples
      from the same cat (collected during 90 min of stimulation) showed little change
      in protein pattern apart from a fall in total protein content. Following 2-DE,
      the major protein (M(r) 30,000) appeared as a complex array of at least eight
      spots in two tiers (pI 5.2-6.2; M(r) 28,000 and 32,000). The characteristics of
      this protein are discussed with reference to allergy to cats.

PMID- 8137799
TI  - Affinity maturation of anti-hapten antibodies in a single mouse analyzed by two
      dimensional affinity electrophoresis.
AB  - Affinity maturation of anti-hapten antibodies in an inbred mouse (BALB/c) was
      analyzed by two-dimensional affinity electrophoresis (2D-AEP) in which the
      antibodies specific to a hapten of dinitrophenyl (DNP) group were separated into
      a large number of IgG families according to the differences in their isoelectric
      points (pI) and in their affinities for the ligand of DNP immobilized in the gel
      matrices. Each of the IgG families consisted of several spots showing an
      identical affinity for the ligand but different pI, and the spots were
      specifically stained by immunostaining with an anti-murine IgG subclass antibody.
      These results lead us to the conclusion that each of the IgG families is derived
      from a single clone of antibody-producing cells specific to DNP. The mass and
      affinity of the IgG families varied in the course of immunization with DNP
      conjugated chicken serum albumin (DNP-CSA). The first injection of DNP-CSA
      induced a small amount of IgG families showing a wide variety in their affinity
      for DNP. The second injection induced a large amount of IgG families, especially
      of families having a medium affinity for DNP. Additional injections, however, did
      not change the mass or affinity of the IgG families significantly. This suggests
      that an antigen-induced somatic mutation of the immunoglobulin gene does not
      occur frequently to mature the affinity of antibodies by the additional
      injections after the second injection. 2D-AEP enables us to analyze the affinity
      maturation of antibodies in vivo in a single mouse and to document the subclass
      switch of the antibody in the course of immunization.

PMID- 8137800
TI  - An efficient disk based data structure for rapid searching of quantitative two
      dimensional gel databases.
AB  - Fast access of two-dimensional (2-D) gel quantitative databases is important for
      rapid searching for protein differences between sets of 2-D gels from an
      experiment. The GELLAB-II system organizes corresponding spots from the gels in
      the database into reference or "Rspot" sets. These Rspot numeric names index
      fixed regions in the paged composite gel database file. This is adequate for an
      existing database, but has several problems. (i) Building the initial database
      requires guessing how much disk space to pre-allocate for each corresponding spot
      (i.e. spots from different gels). If it ever runs out of pre-allocated space
      during this process, it must expand the size of each corresponding set of spots
      copying the old database data into the new in-place on the disk. (ii) When adding
      new gels or editing the database, if a new spot is created, the system may also
      go into this expansion mode. The time spent and wasted disk space can be
      appreciable--depending on the size of the database (order of 100 gel database).
      (iii) Because each set of corresponding spots is the same size, we waste space in
      most spot sets since they do not require the additional space a few spot sets
      require which contain additional fragmented spots. We present a new low-level
      disk object-based structure and algorithm, paged indexed buckets (PIB), which
      optimizes disk space usage while having similar retrieval speed to the original
      method.

PMID- 8137801
TI  - A fast spot segmentation algorithm for two-dimensional gel electrophoresis
      analysis.
AB  - An important issue in the automation of two-dimensional gel electrophoresis image
      analysis is the detection and quantification of protein spots. A spot
      segmentation algorithm must detect, define the extent of, and measure the
      integrated density of spots under a wide variety of actual gel image conditions.
      Besides these functions, the algorithm must be memory efficient to be able to
      process very large gel images and do this in a reasonable amount of computation
      time on low-cost computers, such as workstations and personal computers. We have
      developed a fast spot segmentation algorithm, extending the GELLAB-II segmenter,
      which extracts spots in a single raster scanning pass through the gel image. The
      performance analysis of the algorithm will be given in the paper as well as a
      discussion of the algorithm.

PMID- 8137802
TI  - A nonlinear wide-range immobilized pH gradient for two-dimensional
      electrophoresis and its definition in a relevant pH scale.
AB  - A new nonlinear immobilized pH gradient (IPG) is proposed as the first dimension
      for two-dimensional electrophoresis. In comparison to conventional carrier
      ampholyte techniques, it offers better resolution and greater reproducibility
      whilst allowing application of higher protein loads. Furthermore, we have checked
      and supplemented existing data on pK values for the immobilized groups in the
      presence of 8M urea. This is necessary for pH gradients to be defined in a pH
      scale relevant to the focusing conditions such that spot positions can be related
      to amino acid compositions. The data will allow definition of pH scales for the
      temperature range 10-25 degrees C and for a pH range covering the major part of
      the nonlinear pH gradient. With the latter, focusing positions are neither
      influenced by urea concentration nor by the choice or the concentration of
      detergent or carrier ampholyte. Temperature is the only parameter affecting
      focusing reproducibility and here any changes in focusing positions can be
      related to the amino acid compositions of peptides.

PMID- 8137803
TI  - Two-dimensional electrophoresis as an aid in the analysis of the clonality of
      immunoglobulins.
AB  - In this paper, we summarize our five-year observation of two-dimensional
      polyacrylamide gel electrophoretic (2-D PAGE) analysis of immunoglobulin (Ig)
      light (L) chain patterns on serum/plasma and/or purified human Ig, and compare
      this technique with agarose electrophoresis and/or immunofixation examination.
      Polyclonal Ig L chains were seen as large "fuzzy" areas with several zones of
      high density. The majority (71%) of the monoclonal Ig L chains of monoclonal
      gammopathy detected by conventional electrophoresis appeared as a single large
      and well-defined spot on 2-D PAGE analysis, with the remaining appearing as
      multiple spots. The presence of oligoclonal Ig, reflected by multiple spots in 2
      D PAGE, and several bands in immunofixation, was observed in 5 of 26 patients
      after allogeneic bone marrow transplantation and in 5 patients with tumors. In
      the majority (77%) of hypergammaglobulinemia, L chains appeared as a wide spread
      of small and well-defined spots in 2-D PAGE analysis. This pattern suggested
      oligoclonal Ig-secreting B cell clone expansion, and corresponding abnormalities
      were not detected with immunofixation. 2-D PAGE analysis also detected
      oligoclonal Ig expansions whereas conventional electrophoretic examination was
      normal in 10 additional patients after bone marrow transplantation, and in 6 of
      10 immunocompetent patients with acute severe infections. Analysis of the Ig L
      chain pattern of a severe combined immune-deficient mouse populated with human
      peripheral blood leukocytes confirmed the skewed human Ig production in the
      model. In summary, 2-D PAGE appears to be a sensitive tool for the analysis of Ig
      diversity in various clinical situations.

PMID- 8137804
TI  - Characterization and quantification of mink serum amyloid A protein using two
      dimensional electrophoresis with immobilized pH gradients.
AB  - Using hydrophobic interaction chromatography, two-dimensional electrophoresis
      with an immobilized pH gradient in the first dimension and semidry blotting,
      three isoforms of mink serum amyloid A protein (SAA) were characterized and
      studied during chronic inflammation. Compared to conventional methods that have
      been applied to SAA, the major advantages of the present combination of methods
      are: (i) use of small serum volumes, (ii) rapid extraction, (iii) high
      resolution, and (iv) high yield of proteins.

PMID- 8137805
TI  - Micropreparative two-dimensional electrophoresis allowing the separation of
      samples containing milligram amounts of proteins.
AB  - We describe some simple modifications to the micropreparative two-dimensional (2
      D) electrophoresis procedure using immobilized pH gradients in the first
      dimension and sodium dodecyl sulfate-electrophoresis in the second dimension. The
      geometry of the immobilized pH gradient strips has been changed to allow the use
      of large sample application cups that can accommodate greater sample volumes. The
      use of narrow range immobilized pH gradients with a large sample loading volume
      allows an efficient resolubilization of polypeptides after the first dimension.
      As a result, the vertical streaking caused by too high a protein concentration is
      eliminated in the second dimension. Protein identification by N-terminal
      sequencing is facilitated by the large protein load (1-15 mg) which can be
      employed using this modification. Spots not normally detectable on conventional
      analytical 2-D maps, even with sensitive silver staining, are observed. Results
      for plasma and liver proteins are shown.

PMID- 8137806
TI  - Use of Rotofor in two-dimensional electrophoretic analysis: identification of a
      100 kDa monoclonal IgG heavy chain in myeloma serum.
AB  - After preparative nondenaturing isoelectric focusing in a Rotofor of 1 mL human
      serum which showed on two-dimensional electrophoresis a monoclonal kappa light
      chain pI < 5.0, the monoclonal kappa light chain was identified in the tubes with
      pH 7.29-pH 6.96, indicating that the chain was not free and was most likely part
      of an immunoglobulin molecule. The combined fractions of the Rotofor were
      concentrated back to 1 mL and aliquots were separated by two-dimensional
      electrophoresis, followed by Western blotting. Enzyme immunoassay of the blot
      with A' human IgG (gamma chain specific) revealed a monoclonal heavy chain at a
      molecular size of approximately 100 kDa. Diffuse areas at 50 kDa (the attributed
      size of gamma heavy chain), 100 kDa, and 150 kDa were stained also, but the
      strong, restricted (picket fence) bands indicating a monoclonal pattern were at
      100 kDa. The monoclonal light chain appears to be part of a large or dimeric IgG
      molecule.

PMID- 8137807
TI  - Colloidal carriers for intravenous drug targeting: plasma protein adsorption
      patterns on surface-modified latex particles evaluated by two-dimensional
      polyacrylamide gel electrophoresis.
AB  - Targeting to specific sites of the body via colloidal carriers is sought in order
      to reduce drug side effects. The adsorption of plasma proteins on intravenously
      injected particles is regarded as the key factor in explaining their organ
      distribution: total bound protein, or, more likely, the presence of specific
      proteins and their conformation, are expected to influence macrophage uptake.
      Polystyrene beads, 60 nm in diameter, were used as model carriers; their surface
      was differentially modified by adsorption of increasingly hydrophilic block
      copolymers, poloxamers 184, 188 and 407. After incubation in plasma, the patterns
      of protein adsorption onto coated beads were analyzed by high-resolution two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE). The behavior of some
      representative proteins was monitored, including albumin, fibrinogen, IgG, factor
      B and the apolipoproteins, A-I, A-IV, C-III, E and J. The more hydrophobic the
      particles, the larger the total amount of bound protein. However, this
      correlation was not valid for all of the analyzed protein species, which proves
      that it is insufficient to look only at physicochemical data to predict organ
      distribution. On the contrary, it is essential to use 2-D PAGE to establish the
      correlation between adsorbed proteins and carrier behavior in vivo.

PMID- 8137808
TI  - Crystal structure of the ribosomal protein S6 from Thermus thermophilus.
AB  - The amino acid sequence and crystal structure of the ribosomal protein S6 from
      the small ribosomal subunit of Thermus thermophilus have been determined. S6 is a
      small protein with 101 amino acid residues. The 3D structure, which was
      determined to 2.0 A resolution, consists of a four-stranded anti-parallel beta
      sheet with two alpha-helices packed on one side. Similar folding patterns have
      been observed for other ribosomal proteins and may suggest an original RNA
      interacting motif. Related topologies are also found in several other nucleic
      acid-interacting proteins and based on the assumption that the structure of the
      ribosome was established early in the molecular evolution, the possibility that
      an ancestral RNA-interacting motif in ribosomal proteins is the evolutionary
      origin for the nucleic acid-interacting domain in large classes of ribonucleic
      acid binding proteins should be considered.

PMID- 8137809
TI  - Three-dimensional structure of 6-pyruvoyl tetrahydropterin synthase, an enzyme
      involved in tetrahydrobiopterin biosynthesis.
AB  - The crystal structure of rat liver 6-pyruvoyl tetrahydropterin synthase has been
      solved by multiple isomorphous replacement and refined to a crystallographic R
      factor of 20.4% at 2.3 A resolution. 6-Pyruvoyl tetrahydrobiopterin synthase
      catalyses the conversion of dihydroneopterin triphosphate to 6-pyruvoyl
      tetrahydropterin, the second of three enzymatic steps in the synthesis of
      tetrahydrobiopterin from GTP. The functional enzyme is a hexamer of identical
      subunits. The 6-pyruvoyl tetrahydropterin synthase monomer folds into a
      sequential, four-stranded, antiparallel beta-sheet with a 25 residue, helix
      containing insertion between strands 1 and 2 at the bottom of the molecule, and a
      segment between strands 2 and 3 forming a pair of antiparallel helices, layered
      on one side of the beta-sheet. Three 6-pyruvoyl tetrahydropterin synthase
      monomers form an unusual 12-stranded antiparallel beta-barrel by tight
      association between the N- and C-terminal beta-strands of two adjacent subunits.
      The barrel encloses a highly basic pore of 6-12 A diameter. Two trimers associate
      in a head-to-head fashion to form the active enzyme complex. The substrate
      binding site is located close to the trimer-trimer interface and comprises
      residues from three monomers: A, A' and B. A metal-binding site in the substrate
      binding pocket is formed by the three histidine residues 23, 48 and 50 from one 6
      pyruvoyl tetrahydropterin synthase subunit. Close to the metal, but apparently
      not liganding it, are residues Cys42, Glu133 (both from A) and His89 (from B),
      which might serve as proton donors and acceptors during catalysis.

PMID- 8137810
TI  - The X-ray crystal structure of the catalytic domain of human neutrophil
      collagenase inhibited by a substrate analogue reveals the essentials for
      catalysis and specificity.
AB  - Matrix metalloproteinases are a family of zinc endopeptidases involved in tissue
      remodelling. They have been implicated in various disease processes including
      tumour invasion and joint destruction. These enzymes consist of several domains,
      which are responsible for latency, catalysis and substrate recognition. Human
      neutrophil collagenase (PMNL-CL, MMP-8) represents one of the two 'interstitial'
      collagenases that cleave triple helical collagens types I, II and III. Its 163
      residue catalytic domain (Met80 to Gly242) has been expressed in Escherichia coli
      and crystallized as a non-covalent complex with the inhibitor Pro-Leu-Gly
      hydroxylamine. The 2.0 A crystal structure reveals a spherical molecule with a
      shallow active-site cleft separating a smaller C-terminal subdomain from a bigger
      N-terminal domain, composed of a five-stranded beta-sheet, two alpha-helices, and
      bridging loops. The inhibitor mimics the unprimed (P1-P3) residues of a
      substrate; primed (P1'-P3') peptide substrate residues should bind in an extended
      conformation, with the bulky P1' side-chain fitting into the deep hydrophobic S1'
      subsite. Modelling experiments with collagen show that the scissile strand of
      triple-helical collagen must be freed to fit the subsites. The catalytic zinc ion
      is situated at the bottom of the active-site cleft and is penta-coordinated by
      three histidines and by both hydroxamic acid oxygens of the inhibitor. In
      addition to the catalytic zinc, the catalytic domain harbours a second, non
      exchangeable zinc ion and two calcium ions, which are packed against the top of
      the beta-sheet and presumably function to stabilize the catalytic
      domain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137811
TI  - Solution structure of GAP SH3 domain by 1H NMR and spatial arrangement of
      essential Ras signaling-involved sequence.
AB  - Src homology 3 (SH3) domains are found in numerous cytoplasmic proteins involved
      in intracellular signal transduction. We used 2-D 1H NMR to determine the
      structure of the SH3 domain of the guanosine triphosphatase-activating protein
      (GAP), an essential component of the Ras signaling pathway. The structure of the
      GAP SH3 domain (275-350) was found to be a compact beta-barrel made of six
      antiparallel beta-strands arranged in two roughly perpendicular beta-sheets with
      the acidic residues located at the surface of the protein. The Trp317, Trp319,
      Thr321 and Leu323 residues belonging to the sequence (317-326), which was shown
      to be essential for Ras signaling, formed two nearby lipophilic bulges followed
      by a hydrophilic domain (Arg324-Asp326). These structural data could be used to
      characterize the still unidentified downstream components of GAP, which are
      involved in Ras signaling, and to rationally design inhibitors of this pathway.

PMID- 8137812
TI  - Intron positions in actin genes seem unrelated to the secondary structure of the
      protein.
AB  - A catalogue of intron positions along the coding sequence was assembled from the
      large number of actin genes known for different eukaryotes. 36 positions in the
      amino acid sequence were compared with the known three-dimensional structure of
      actin. At least 20 but not more than 23 intron positions are at the start or end
      of a secondary structural element (beta-strand, alpha-helix or 3/10 helix) while
      eight positions interrupt such an element. Statistical analysis shows that due to
      the large number of end positions the boundaries of secondary structural elements
      are not correlated with the intron positions. In addition, the observed intron
      pattern seems compatible with the null hypothesis, i.e. intron positions are
      randomly distributed along the actin sequence.

PMID- 8137813
TI  - Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis.
AB  - Small GTPases of the rab family control distinct steps of intracellular
      transport. The function of their GTPase activity is not completely understood. To
      investigate the role of the nucleotide state of rab5 in the early endocytic
      pathway, the effects of two mutants with opposing biochemical properties were
      tested. The Q79L mutant of rab5, analogous with the activating Q61L mutant of p21
      ras, was found to have a strongly decreased intrinsic GTPase activity and was,
      unlike wild-type rab5, found mainly in the GTP-bound form in vivo. Expression of
      this protein in BHK and HeLa cells led to a dramatic change in cell morphology,
      with the appearance of unusually large early endocytic structures, considerably
      larger than those formed upon overexpression of wild-type rab5. An increased rate
      of transferrin internalization was observed in these cells, whereas recycling was
      inhibited. Cytosol containing rab5 Q79L stimulated homotypic early endosome
      fusion in vitro, even though it contained only a small amount of the
      isoprenylated protein. A different mutant, rab5 S34N, was found, like the
      inhibitory p21-ras S17N mutant, to have a preferential affinity for GDP.
      Overexpression of rab5 S34N induced the accumulation of very small endocytic
      profile and inhibited transferrin endocytosis. This protein inhibited fusion
      between early endosomes in vitro. The opposite effects of the rab5 Q79L and S34N
      mutants suggest that rab5:GTP is required prior to membrane fusion, whereas GTP
      hydrolysis by rab5 occurs after membrane fusion and functions to inactivate the
      protein.

PMID- 8137814
TI  - VPS21 encodes a rab5-like GTP binding protein that is required for the sorting of
      yeast vacuolar proteins.
AB  - Many of the vacuolar protein sorting (vps) mutants of Saccharomyces cerevisiae
      exhibit severe defects in the sorting of vacuolar proteins but still retain near
      normal vacuole morphology. The gene affected in one such mutant, vps21, has been
      cloned and found to encode a member of the ras-like GTP binding protein family.
      Sequence comparisons with other known GTP binding proteins indicate that Vps21p
      is unique but shares striking similarity with mammalian rab5 proteins (> 50%
      identity and > 70% similarity). Regions with highest similarity are clustered
      within the putative GTP binding motifs and the proposed effector domains of the
      Vps21/rab5 proteins. Point mutations constructed within these conserved regions
      inactivate Vps21p function; the mutant cells missort and secrete the soluble
      vacuolar hydrolase carboxypeptidase Y (CPY). Cells carrying a complete deletion
      of the VPS21 coding sequence (i) are viable but exhibit a growth defect at 38
      degrees C, (ii) missort multiple vacuolar proteins, (iii) accumulate 40-50 nm
      vesicles and (iv) contain a large vacuole. VPS21 encodes a 22 kDa protein that
      binds GTP and fractionates with subcellular membranes. Mutant analysis indicates
      that the association with a membrane(s) is dependent on geranylgeranylation of
      the C-terminal cysteine residue(s) of Vps21p. We propose that Vps21p functions in
      the targeting and/or fusion of transport vesicles that mediate the delivery of
      proteins to the vacuole.

PMID- 8137815
TI  - Targeting of proteins to the thylakoids by bipartite presequences: CFoII is
      imported by a novel, third pathway.
AB  - The CFoII subunit of the ATP synthase is an integral component of the thylakoid
      membrane which is synthesized in the cytosol with a bipartite, lumen-targeting
      presequence similar in structural terms to those of imported lumenal proteins
      such as plastocyanin. This presequence is shown to possess a terminal cleavage
      site for the thylakoidal processing peptidase, but no intermediate site for the
      stromal processing peptidase. The integration of CFoII into the thylakoid
      membrane of Pisum sativum has been analysed using in vitro assays for the import
      of proteins into intact chloroplasts or isolated thylakoids. Efficient
      integration into thylakoids is observed in the light and dark, and the
      integration process does not require the presence of either stromal extracts or
      nucleoside triphosphates. The uncoupler nigericin inhibits integration only very
      slightly, indicating that the thylakoidal delta pH does not play a significant
      role in the integration mechanism. In each of these respects, the requirements
      for CFoII integration differ notably from those determined for integration of the
      light-harvesting chlorophyll-binding protein of photosystem II. The integration
      mechanism also differs significantly from the two mechanisms involved in the
      translocation of lumenal proteins across the thylakoid membrane, since one of
      these processes requires the presence of stromal protein factors and ATP, and the
      other mechanism is dependent on the thylakoidal delta pH. This conclusion is
      reinforced by the finding that saturation of the translocation system for the
      precursor to the lumenal 23 kDa oxygen-evolving complex protein does not affect
      integration of CFoII into thylakoids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137816
TI  - Expression of the human glycine receptor alpha 1 subunit in Xenopus oocytes:
      apparent affinities of agonists increase at high receptor density.
AB  - The inhibitory glycine receptor (GlyR) is a ligand-gated chloride channel, which
      mediates post-synaptic inhibition in spinal cord and other brain regions.
      Heterologous expression of the ligand binding alpha subunits of the GlyR
      generates functional agonist-gated chloride channels that mimic most of the
      pharmacological properties of the receptor in vivo. Here, nuclear injection into
      Xenopus oocytes of a human alpha 1 subunit cDNA, engineered for efficient
      expression, was used to create GlyR channels over a wide density range, resulting
      in whole-cell glycine currents of 10 nA to 25 microA. Notably, the pharmacology
      of these channels changed at high expression levels, with the appearance of a
      novel receptor subpopulation of 5- to 6-fold higher apparent agonist affinity at
      current values > 4 microA. The low-affinity receptors were readily blocked by nM
      concentrations of the competitive antagonist strychnine, whereas the high
      affinity receptors were more resistant to antagonism by this alkaloid.
      Picrotoxinin, a chloride channel blocker, inhibited both GlyR populations with
      equal potency. Our data suggest that receptor interactions, occurring at high
      receptor density, modify the agonist response of the GlyR. This phenomenon may
      contribute to neurotransmitter efficacy at fast synapses.

PMID- 8137817
TI  - Agonist-specific coupling of a cloned Drosophila octopamine/tyramine receptor to
      multiple second messenger systems.
AB  - A cloned seven transmembrane-spanning Drosophila octopamine/tyramine receptor,
      permanently expressed in a Chinese hamster ovary cell line, both inhibits
      adenylate cyclase activity and leads to the elevation of intracellular Ca2+
      levels by separate G-protein-coupled pathways. Agonists of this receptor
      (octopamine and tyramine), differing by only a single hydroxyl group in their
      side chain, may be capable of differentially coupling it to different second
      messenger systems. Thus, a single receptor may have a different pharmacological
      profile depending on which second messenger system is used to assay its efficacy.

PMID- 8137818
TI  - Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization
      through distinct pathways.
AB  - Stimulation of B lymphocytes through their antigen receptor (BCR) results in
      rapid increases in tyrosine phosphorylation on a number of proteins and induces
      both an increase of phosphatidylinositol and mobilization of cytoplasmic free
      calcium. The BCR associates with two classes of tyrosine kinase: Src-family
      kinase (Lyn, Fyn, Blk or Lck) and Syk kinase. To dissect the functional roles of
      these two types of kinase in BCR signaling, lyn-negative and syk-negative B cell
      lines were established. Syk-deficient B cells abolished the tyrosine
      phosphorylation of phospholipase C-gamma 2, resulting in the loss of both
      inositol 1,4,5-trisphosphate (IP3) generation and calcium mobilization upon
      receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayed
      and slow Ca2+ mobilization, despite the normal kinetics of IP3 turnover. These
      results demonstrate that Syk mediates IP3 generation, whereas Lyn regulates Ca2+
      mobilization through a process independent of IP3 generation.

PMID- 8137819
TI  - STF-IL-4: a novel IL-4-induced signal transducing factor.
AB  - The mechanism by which interleukin-4 (IL-4) regulates the expression of
      particular genes is unknown. We have determined that IL-4 induces a DNA binding
      factor (termed STF-IL-4) which has a strong affinity for an IFN-gamma activation
      site (GAS). Interestingly, STF-IL-4 also binds to the IL-4 responsive promoter
      for the Ig heavy chain germline epsilon transcript. The IL-4 dependent activation
      of STF-IL-4 is rapid, does not require protein synthesis and results in the
      sequential appearance of binding activity first in the cytoplasm and then later
      in the nucleus. Activation of STF-IL-4 is sensitive to tyrosine kinase inhibitors
      and the active factor is tyrosine phosphorylated. This pattern of activation is
      similar to the activation of interferon-induced transcription factors. STF-IL-4
      appears to be a new member of a growing family of cytokine-induced
      transcriptional regulators.

PMID- 8137820
TI  - Down-regulation of wild-type p53 activity interferes with apoptosis of IL-3
      dependent hematopoietic cells following IL-3 withdrawal.
AB  - Overexpression of wild-type p53 in p53-deficient leukemic cells induces
      apoptosis, which can be inhibited by hematopoietic survival factors. This
      suggests that p53 may contribute to survival factor dependence. To assess the
      role of wild-type p53 in mediating apoptosis following survival factor
      withdrawal, we interfered with endogenous p53 activity in interleukin-3 (IL-3)
      dependent cells. Extended survival without IL-3 was conferred by recombinant
      retroviruses encoding either a full-length p53 mutant or a C-terminal p53
      miniprotein, both of which can act as negative-dominant inhibitors of wild-type
      p53. On the other hand, excess wild-type p53 activity failed to elicit apoptosis
      as long as IL-3 was present. We propose that p53 is a positive, though not
      exclusive, mediator of survival factor dependence in hematopoietic cells.

PMID- 8137821
TI  - Expression of LIF in transgenic mice results in altered thymic epithelium and
      apparent interconversion of thymic and lymph node morphologies.
AB  - Leukemia inhibitory factor (LIF) is a cytokine involved in embryonic and
      hematopoietic development. To investigate the effects of LIF on the lymphoid
      system, we generated a line of transgenic mice that expresses diffusible LIF
      protein specifically in T cells. These mice display two categories of phenotype
      that were not previously attributed to LIF overexpression. First, they display B
      cell hyperplasia, polyclonal hypergammaglobulinemia and mesangial proliferative
      glomerulonephritis, defects similar to those described for transgenic mice
      overexpressing the functionally related cytokine, interleukin-6. Secondly, the
      LIF transgenic mice display novel thymic and lymph node abnormalities. In the
      thymus, cortical CD4+CD8+ lymphocytes are lost, while numerous B cell follicles
      develop. Peripheral lymph nodes contain a vastly expanded CD4+CD8+ lymphocyte
      population. Furthermore, the thymic epithelium is profoundly disorganized,
      suggesting that disruption of stroma-lymphocyte interactions is responsible for
      many observed defects. Transplantation of transgenic bone marrow into wild type
      recipients transfers both the thymic and lymph node defects. However,
      transplantation of wild type marrow into transgenic recipients rescues the lymph
      node abnormality, but not the thymic defect, indicating the thymic epithelium is
      irreversibly altered. Our observations are consistent with a role for LIF in
      maintaining a functional thymic epithelium that will support proper T cell
      maturation.

PMID- 8137822
TI  - A single amino acid substitution in the exoplasmic domain of the human growth
      hormone (GH) receptor confers familial GH resistance (Laron syndrome) with
      positive GH-binding activity by abolishing receptor homodimerization.
AB  - Growth hormone (GH) elicits a variety of biological activities mainly mediated by
      the GH receptor (GHR), a transmembrane protein that, based on in vitro studies,
      seemed to function as a homodimer. To test this hypothesis directly, we
      investigated patients displaying the classic features of Laron syndrome (familial
      GH resistance characterized by severe dwarfism and metabolic dysfunction), except
      for the presence of normal binding activity of the plasma GH-binding protein, a
      molecule that derives from the exoplasmic-coding domain of the GHR gene. In two
      unrelated families, the same GHR mutation was identified, resulting in the
      substitution of a highly conserved aspartate residue by histidine at position 152
      (D152H) of the exoplasmic domain, within the postulated interface sequence
      involved in homodimerization. The recombinant mutated receptor protein was
      correctly expressed at the plasma membrane. It displayed subnormal GH-binding
      activity, a finding in agreement with the X-ray crystal structure data inferring
      this aspartate residue outside the GH-binding domain. However, mAb-based studies
      suggested the critical role of aspartate 152 in the proper folding of the
      interface area. We show that a recombinant soluble form of the mutant receptor is
      unable to dimerize, the D152H substitution also preventing the formation of
      heterodimers of wild-type and mutant molecules. These results provide in vivo
      evidence that monomeric receptors are inactive and that receptor dimerization is
      involved in the primary signalling of the GH-associated growth-promoting and
      metabolic actions.

PMID- 8137823
TI  - Transcriptional activation through the tetrameric complex formation of E4TF1
      subunits.
AB  - Transcription factor E4TF1 is composed of two types of subunit, an ets-related
      DNA binding protein, E4TF1-60, and its associated proteins with four tandemly
      repeated Notch-ankyrin motifs, E4TF1-53 and E4TF1-47. To determine the functional
      domains, we constructed various mutants of the subunits. E4TF1-60 bound to DNA as
      a monomer. The ets domain and its N-terminal flanking region were necessary to
      recognize the specific DNA sequence. The 48 amino acids at the E4TF1-60 C
      terminus were required for interaction with the other type of subunit. E4TF1-53
      and E4TF1-47 share the N-terminal 332 amino acids but differ at the C-termini.
      They interacted with E4TF1-60 through the N-terminal flanking region to form a
      heterodimer. E4TF1-53 dimerized with itself, whereas E4TF1-47 did not. The C
      terminal region specific for E4TF1-53 was required for the dimerization.
      Therefore, heterodimers composed of E4TF1-53 and E4TF1-60 were further dimerized,
      resulting in the formation of a tetrameric complex, which stimulated
      transcription in vitro. Heterodimers of E4TF1-47 and E4TF1-60 weakly stimulated
      transcription in vitro. The results indicated that the tetrameric complex
      formation of E4TF1 subunits was necessary to activate transcription efficiently
      in vitro.

PMID- 8137824
TI  - Heterodimerization of the yeast MATa1 and MAT alpha 2 proteins is mediated by two
      leucine zipper-like coiled-coil motifs.
AB  - The yeast Saccharomyces cerevisiae has three cell types distinguished by the
      proteins encoded in their mating type (MAT) loci: the a and alpha haploids, which
      express the DNA binding proteins a1 and alpha 1 and alpha 2, respectively, and
      the a/alpha diploid which expresses both a1 and alpha 2 proteins. In a/alpha
      cells, a1-alpha 2 heterodimers repress haploid-specific genes, while alpha 2
      homodimers repress a-specific genes, indicating a dual regulatory function for
      alpha 2 in mating type control. a1 does not form homodimers. We have identified
      two sequences in the alpha 2 N-terminal domain which contain the 3,4-hydrophobic
      heptad repeat pattern characteristic of coiled-coils. Mutational analyses show
      that both sequences are important to a1-alpha 2 heterodimerization. We propose
      that these two sequences associate in a coiled-coil-like manner with a sequence
      within a1 which bears two adjacent, overlapping 3,4-hydrophobic heptad repeats.
      This model, which describes a novel dimerization motif for homeodomain proteins,
      also provides a mechanism by which a1-a1 homodimerization is prevented.

PMID- 8137825
TI  - Dimerization interfaces formed between the DNA binding domains determine the
      cooperative binding of RXR/RAR and RXR/TR heterodimers to DR5 and DR4 elements.
AB  - We have previously reported that the binding site repertoires of heterodimers
      formed between retinoid X receptor (RXR) and either retinoic acid receptor (RAR)
      or thyroid hormone receptor (TR) bound to response elements consisting of
      directly repeated PuG(G/T)TCA motifs spaced by 1-5 bp [direct repeat (DR)
      elements 1-5] are highly similar to those of their corresponding DNA binding
      domains (DBDs). We have now mapped the dimerization surfaces located in the DBDs
      of RXR, RAR and TR, which are responsible for cooperative interaction on DR4 (RXR
      and TR) and DR5 (RXR and RAR). The D-box of the C-terminal CII finger of RXR
      provides one of the surfaces which is specifically required for the formation of
      the heterodimerization interfaces on both DR4 and DR5. Heterodimerization with
      the RXR DBD on DR5 specifically requires the tip of the RAR CI finger as the
      complementary surface, while a 7 amino acid sequence encompassing the 'prefinger
      region', but not the TR CI finger, is specifically required for efficient
      dimerization of TR and RXR DBDs on DR4. Importantly, DBD swapping experiments
      demonstrate not only that the binding site repertoires of the full-length
      receptors are dictated by those of their DBDs, but also that the formation of
      distinct dimerization interfaces between the DBDs are the critical determinants
      for cooperative DNA binding of these receptors to specific DRs.

PMID- 8137826
TI  - The dimerization interfaces formed between the DNA binding domains of RXR, RAR
      and TR determine the binding specificity and polarity of the full-length
      receptors to direct repeats.
AB  - Heterodimers of retinoid X receptor (RXR) and retinoic acid receptor (RAR) bind
      preferentially to directly repeated elements with spacing of two (DR2) or five
      (DR5) base pairs, due to the specific heterocooperative interaction of their DNA
      binding domains (DBDs) on these elements. We have demonstrated in the
      accompanying paper that the heterodimeric DBD interface that is responsible for
      the cooperative binding to DR5 elements, specifically involves the D-box of the
      RXR CII finger and the tip of the RAR CI finger. We show here that a second type
      of dimerization interface, which specifically implicates the RAR T-box and the
      RXR CII finger to the exclusion of the D-box, determines the selective binding to
      DR2 elements. Interestingly, the same type of dimerization interface (RXR T-box
      and CII finger) is responsible for the cooperative binding of homodimers of the
      RXR DBD to DR1 elements. Based on the three-dimensional structure of the
      glucocorticoid receptor DBD, modeling of RXR/RAR, RXR/TR and RXR/RXR DBD
      cooperative interactions predicts that in all cases the DBD contributing the CII
      finger, i.e. that of RXR, has to be positioned 5' to its cooperatively bound
      partner. This binding polarity of the DBDs is conferred upon the full-length
      receptors, since crosslinking experiments indicate that RXR is always 5' to RAR
      in complexes between either DR5 or DR2 and RXR/RAR heterodimers. The possible
      significance of these observations for transactivation by retinoic acid receptors
      is discussed.

PMID- 8137827
TI  - The E6/E7 promoter of extrachromosomal HPV16 DNA in cervical cancers escapes from
      cellular repression by mutation of target sequences for YY1.
AB  - Human papillomavirus type 16 (HPV16) induces squamous intraepithelial lesions of
      the cervical mucosa which may develop into invasive cancer. The expression of
      viral oncogenes in advanced neoplasias appears increased relative to the
      proliferating cell layers of low grade lesions raising questions about molecular
      mechanisms of deregulation of transcription. In a lymph node metastasis of a
      cervical cancer, we observed full-length HPV16 plasmids and molecules with a
      small deletion, which was mapped to the long control region (LCR). Both wild type
      and shortened LCR were amplified by PCR, cloned into the promoter test plasmid
      pBLCAT6 and sequenced to identify a 107 bp deletion from position 7794 to 7901 in
      the short LCR. CAT expression in cervical cancer-derived HT3, SiHa and CaSki
      cells appeared 5- to 6-fold increased under the control of the short LCR. This
      could be traced back to elevated levels of mRNA initiated at the viral oncogene
      promoter. A slight further increase in CAT expression was noted in the presence
      of the HPV16 E2 protein which is probably due to the deletion of one E2 binding
      site and consequent relief from E2 repression. Computer-assisted sequence
      analysis and band-shift experiments with purified YY1 protein and wild type or
      mutated oligonucleotides identified four binding sites for this cellular
      transcriptional repressor within the promoter-proximal segment of the HPV16 LCR,
      three of which were removed by the deletion. A LCR fragment comprising these YY1
      binding sites was cloned in front of the heterologous thymidine kinase gene
      promoter and suppressed CAT expression 3- to 4-fold.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8137828
TI  - An autonomous N-terminal transactivation domain in Fos protein plays a crucial
      role in transformation.
AB  - To date, three functional domains have been defined in c-Fos and v-Fos proteins
      and have been shown to play a role in transactivation: the leucine zipper
      mediating hetero-dimerization, the basic DNA contact site, and a C-terminally
      located transactivation domain (C-TA) harbouring the HOB1 and HOB2 motifs. While
      the bZip region, consisting of the leucine zipper and the DNA contact site, is
      indispensable for transformation, the C-TA domain is not required and is actually
      altered by internal deletions in the FBR-MuSV. We now show that the N-terminal
      regions of c-Fos and v-Fos contain a second transactivation domain (N-TA). A
      functionally crucial motif within the N-TA domain, termed NTM, was pinpointed to
      a approximately 25 amino acid stretch around positions 60-84 which is highly
      conserved in FosB. Analysis of LexA fusion proteins showed that the N-TA domains
      of both c-Fos and FosB function in an autonomous fashion in both fibroblasts and
      yeast. Most importantly, deletion of the NTM motif impairs the transforming
      properties of v-Fos. Apart from the bZip region, the N-TA domain is the only
      functional domain required for transformation by v-Fos, at least when its
      expression is driven by the strong FBR-MuSV-LTR promoter.

PMID- 8137829
TI  - Translation of 15-lipoxygenase mRNA is inhibited by a protein that binds to a
      repeated sequence in the 3' untranslated region.
AB  - During red blood cell differentiation, the mRNA encoding rabbit erythroid 15
      lipoxygenase (LOX) is synthesized in the early stages of erythropoiesis, but is
      only activated for translation in peripheral reticulocytes. Erythroid LOX, which
      like other lipoxygenases catalyses the degradation of lipids, is unique in its
      ability to attack intact phospholipids and is the main factor responsible for the
      degradation of mitochondria during reticulocyte maturation. Strikingly, rabbit
      erythroid LOX mRNA has 10 tandem repeats of a slightly varied, pyrimidine-rich 19
      nt motif in its 3'-untranslated region (3'-UTR). In this study we demonstrate,
      using gel retardation and UV-crosslinking assays, that this 3'-UTR segment
      specifically binds a 48 kDa reticulocyte protein. Furthermore, the interaction
      between the 3'-UTR LOX repeat motif and the 48 kDa protein, purified to
      homogeneity by specific RNA chromatography, is shown to be necessary and
      sufficient for specific translational repression of LOX as well as reporter mRNAs
      in vitro. To our knowledge this is the first case in which translation,
      presumably at the initiation step, is regulated by a defined protein-RNA
      interaction in the 3'-UTR.

PMID- 8137830
TI  - Residues within transmembrane segment M2 determine chloride conductance of
      glycine receptor homo- and hetero-oligomers.

PMID- 8137831
TI  - The atypical M2 segment of the beta subunit confers picrotoxinin resistance to
      inhibitory glycine receptor channels.

PMID- 8137832
TI  - Deprenyl and the issue of neuroprotection.

PMID- 8137833
TI  - Borderzone infarct subtypes: preliminary study of the presumed mechanism.
AB  - Whether watershed infarcts and internal junctional infarcts have different
      mechanisms remains unknown. Of 493 consecutive patients with ischemic stroke or
      transient ischemic attack, 26 had 1 watershed infarct or more (8 anterior and 21
      posterior) and 18 had 1 internal junctional infarct or more. Patients with
      watershed infarcts were more likely to have arterial hypertension [95% confidence
      intervals of odds ratio (CIOR): 1.04-6.15] and internal carotid artery stenosis >
      50% (95% CIOR: 1.03-7.12) than patients without borderzone infarcts. Patients
      with internal junctional infarcts were more likely to have heart diseases than
      patients without borderzone infarcts (95% CIOR: 1.46-10.52). This preliminary
      study suggests that both subtypes of borderzone infarcts probably have different
      mechanisms.

PMID- 8137834
TI  - Stroke associated with methamphetamine inhalation.
AB  - Seven patients (all men, mean age 32 years, range 17-47) with stroke following
      methamphetamine inhalation were collected during the last 2 years. Like oral or
      intravenous abusers, our patients had more hemorrhagic (n = 5) than ischemic
      strokes (n = 2). Cases of intracerebral hemorrhage (ICH) were lobar (n = 3),
      caudate (n = 1) or putaminal (n = 1), whereas the infarctions were both in the
      middle cerebral artery region. Each stroke event occurred within 3 days after
      drug use. Three patients had hypertension on admission. Though young in age, most
      patients had multiple stroke risk factors. In 3 patients with ICH, we also found
      small, low attenuated lesions on the brain computed tomography, however, without
      clinical correlations. Except for arteriovenous malformation in 1 patient, all
      angiograms failed to show vasculopathy or vasospasm. Contrary to what one might
      surmise from previously published reports, methamphetamine inhalation is at least
      as likely to produce ICH as it is to produce brain infarction.

PMID- 8137835
TI  - Correlation of altered Q-T interval and sympathetic nervous system dysfunction in
      diabetic autonomic neuropathy.
AB  - We examined the relationship between the Q-T interval and autonomic dysfunction
      in 74 diabetic patients and age-matched controls. The expected Q-T interval was
      standardized as a function of the R-R interval in 646 healthy controls, and the
      delta Q-T defined as the difference from the expected value. Propranolol
      increased delta Q-T, confirming this as a parameter of autonomic function. No
      relationship between delta Q-T and duration of disease, glucose control,
      retinopathy or proteinuria was observed. However, significant correlations were
      found between the delta Q-T and delay of nerve conduction velocity, orthostatic
      hypotension, altered Valsalva ratio, abnormal Valsalva overshoot, cold pressor
      response, decreased norepinephrine concentration and sympathetic function score
      in diabetic patients.

PMID- 8137836
TI  - Temporary forced laughter after unilateral strokes.
AB  - Forced laughter generally occurs in bilateral or diffuse lesions of the brain and
      is generally associated with pathologic crying. We report the cases of 3 patients
      in whom temporary forced laughter occurred after unilateral supratentorial
      infarction demonstrated by CT scan or MRI. In all cases, the lesion was
      exclusively subcortical and involved the striatocapsular region. For all patients
      the laughter occurred during the recovery phase of motor deficit and was 'pure'
      without associated weeping or other clinical features of pseudobulbar palsy. In
      all cases, the laughter attacks had become much less frequent or had totally
      disappeared 1 or 2 months after the stroke. According to a 'motor' hypothesis, a
      unilateral striatocapsular lesion may lead to temporary deregulation of the
      expression mechanisms.

PMID- 8137837
TI  - New drug treatments in epilepsy.

PMID- 8137838
TI  - Carnitine analysis in normal human red blood cells, plasma, and muscle tissue.
AB  - We studied the distribution of carnitine in different compartments of the human
      body. Esterified and nonesterified carnitine was determined in plasma, red blood
      cells, and muscle tissue of 25 patients with clinically and biochemically normal
      carnitine metabolism. We found a close correlation of plasma and muscle
      carnitine, but carnitine in red blood cells seems to represent a carnitine
      compartment of its own. It is probably less related with fatty acid metabolism of
      the mitochondria than with cell membrane stabilization or buffer function for Na
      K-ATPase.

PMID- 8137839
TI  - Axial myoclonus mediated by the propriospinal tract: a case report.
AB  - We describe a patient with axial myoclonus. Myoclonus first occurred in the upper
      abdominal muscle and spread up to the neck muscle and down to the lower abdominal
      muscle. Physiological studies of the jerks revealed that the myoclonus arose in
      the thoracic spinal cord and spread slowly up and down the spinal cord at about 3
      m/s. We conclude that the myoclonus is mediated by the propriospinal tract.

PMID- 8137840
TI  - Surgical treatment of suprasellar arachnoid cyst.

PMID- 8137841
TI  - Evaluation of patients with suspected herniated lumbar discs with radiculopathy.

PMID- 8137842
TI  - Hemodynamic changes during prolonged laparoscopic surgery.
AB  - 7 healthy pigs, anesthetized with ketamine/azaperon/thiopentone and ventilated
      with O2/N2O by volume control, underwent anterior resection of the descending
      colon by laparoscopic view. During operation of pneumoperitoneum by inflating CO2
      to an abdominal pressure of 14 mm Hg was installed. Immediately (+2 min) after
      the onset of insufflation, both systemic and pulmonary arterial pressure
      increased. However, pulmonary artery pressure started to decrease after 10 min,
      whereas systemic arterial pressure remained elevated until the end of the
      experimental protocol. Left ventricular (LV) pressure and LV dp/dt increased in
      parallel with the systemic arterial pressure. Peak inspiratory pressure and
      central venous pressure increased in parallel with the abdominal pressure. Blood
      gas analysis of arterial and pulmonary blood demonstrated increased pCO2
      associated with mild acidosis. Arterial pO2 did not change significantly
      indicating that the decreased pulmonary distensibility did not endanger the
      oxygenation. Pulmonary pO2 and pulmonary O2 saturation increased early (+10 min)
      after start of insufflation and were stable during the 2 h of observation
      indicating either increased cardiac output or decreased O2 extraction. We
      conclude that the sharp initial rise of both arterial pressures could be the
      effect of a mechanical action, whereas sustained hemodynamic alterations would
      involve complex regulatory mechanisms like an increase of sympathetic activity,
      baroreceptor control, or a response to acidosis. The acute and, in the systemic
      circulation, stable increase of ventricular afterload should be considered in
      patients with underlying cardiac diseases such as ischemic heart disease or
      valvular dysfunction or in patients taking drugs which interfere with normal
      compensatory processes.

PMID- 8137843
TI  - Hemodynamics and hepatic energy metabolism in canine model of acute hepatic
      venous occlusion with mesocaval shunt.
AB  - The relationship between portal hemodynamics and the energy metabolism of the
      liver with acute hepatic venous occlusion (HVO) was investigated by assessing the
      changes in the hepatic blood flow, arterial blood ketone body ratio (AKBR) and
      adenylate energy charge potential (ECP) of the liver tissue in canine model.
      Acute HVO was induced by the ligation of both the supra- and infrahepatic
      inferior vena cava (IVC) over the protruding ends of a heparin-coated
      polyethylene cannula inserted into the IVC. All dogs with only HVO (n = 5) died
      within 30 min. HVO dogs with additional mesocaval (MC) shunt (n = 10) survived
      longer than 7 days, during which time their AKBR were maintained in the normal
      range (over 1.0). ECP was also maintained above the normal level (over 0.850)
      during the 28-day period. Along with increasing portal pressure caused by the
      narrowing of the shunt anastomosis, the hepatic blood flow decrease gradually,
      resulting in a sudden decrease in AKBR and ECP when the portal pressure increased
      over 11 mm Hg. It is suggested that the normalization of portal pressure is one
      of the most important factors for maintaining the hepatic energy metabolism and
      that MC shunt is an effective therapy for maintaining the function of the liver
      with HVO, as long as portal pressure can be kept within normal range.

PMID- 8137844
TI  - Comparison of the effect of conventional highly selective vagotomy and anterior
      gastric wall stapling with posterior truncal vagotomy on the gastric emptying
      rate for solid meals in beagle dogs.
AB  - Anterior gastric wall stapling combined with posterior truncal vagotomy has been
      used as a new and adequate gastric acid output-reducing procedure. Severing the
      posterior vagal trunk as well as stapling the anterior gastric wall could impair
      gastric emptying. In this study, the gastric emptying rate for solid food, using
      a radionuclide technique, has been evaluated in 2 series of canine experiments.
      Compared to the results after conventional highly selective vagotomy, a temporary
      delay in the gastric emptying rate could be found after this new procedure,
      however, completely normalizing 1 year later.

PMID- 8137845
TI  - Evaluating microscopic arterial reconstruction: a comparison of laser-assisted
      versus conventional vascular anastomosis in 70% hepatectomized rat model.
AB  - The influence of deteriorated liver function on the healing process of arterial
      anastomosis was investigated in rats who underwent arterial reconstruction by the
      microscopic surgical techniques of conventional sutured vascular anastomosis
      (CSVA) and laser-assisted vascular anastomosis (LAVA). After 70% hepatectomy, the
      arterial ketone body ratio, reflecting the hepatic mitochondrial redox state, and
      the adenylate energy charges of the platelets, polymorphonuclear leukocytes and
      mononuclear cells, which play an important role in wound healing, were
      significantly lower in hepatectomized rats than in control. Tensile strength and
      bursting pressure with CSVA at the abdominal aortic anastomosis were also
      significantly lower in hepatectomized rats than in control. While CSVA was
      superior to LAVA in tensile strength, bursting pressure and incidence of aneurysm
      formation in nonhepatectomized rats, LAVA tended to show a lower degree of
      disadvantage in hepatectomized rats than CSVA, especially in the incidence of
      calcification at the anastomotic site. It was concluded that LAVA would be a
      useful option in vascular anastomosis, even during extended hepatectomy.

PMID- 8137846
TI  - Macrophage response to experimental implantation of polypropylene prostheses.
AB  - We have assessed the macrophage response to polypropylene mesh (Marlex) implanted
      into the abdominal wall of New Zealand white rabbits, using RAM-11, a monoclonal
      antibody specific for rabbit macrophages. The response diminishes during the
      course of the first 90 days after implantation, although the presence of other
      cell types typical of foreign-body reactions increases. We have also confirmed
      the high degree of integration of the biomaterial into the wall achieved after 9
      weeks. This has been determined using light and scanning electron microscopy.
      Likewise, we have observed the formation of numerous adhesions between the
      polypropylene mesh and the viscera of the abdominal cavity.

PMID- 8137847
TI  - Increased graft survival by utilization of 15-deoxyspergualin in a canine
      pancreatic allotransplantation model.
AB  - The purpose of this study was to evaluate the effectiveness of 15-deoxyspergualin
      (DSG) administration against acute rejection of canine pancreatic allografts.
      Subsequent to partial pancreatic allotransplantation and total extirpation of the
      pancreas, 20 adult mongrel dogs were divided into four groups and treated with
      saline (group 1, controls, n = 5), DSG at 1.0 mg/kg/day (group 2, n = 5), DSG at
      3.0 mg/kg/day (group 3, n = 5), or DSG at 5.0 mg/kg/day (group 4, n = 5) on
      postoperative days 4-7. The graft survival, defined by a fasting serum glucose
      level < 150 mg/dl, was significantly prolonged from 6.2 +/- 1.2 days in group 1
      to 12.4 +/- 2.7 days in group 3 (p < 0.05) and to 16.8 +/- 3.2 days in group 4 (p
      < 0.05). Graft survival was not significantly prolonged in group 2, however. Two
      normoglycemic dogs in group 4 died due to gastrointestinal toxicity, one of the
      most serious side effects of DSG. The observation that the serum insulin levels
      increased in dogs treated with DSG was compatible with dose-dependent graft
      survival and suggested that DSG had no toxic effects on pancreatic endocrine
      function. In group 1 significantly increased thromboxane B2 (TXB2) levels and
      TXB2/6-keto-prostaglandin F1 alpha (PGF1 alpha) ratios were observed on
      postoperative days 3-5 which was thought to reflect acute rejection. Following
      administration of DSG, both TXB2 levels and TXB2/PGF1 alpha ratios were decreased
      on the 5th postoperative day in groups 2-4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137849
TI  - Prognosis after extracorporeal shock wave lithotripsy of radiopaque renal
      calculi: a multivariate analysis.
AB  - To obtain a better understanding of the prognostic factors influencing treatment
      outcome after extracorporeal shock wave lithotripsy (ESWL), a multivariate
      logistic analysis of the data from 246 patients has been undertaken. All of the
      patients were treated with the Dornier lithotriptor HM-3 for radiopaque renal
      calculi. Treatment success was defined as stone-free within 3 months of one ESWL
      session and without adjuvant measures after ESWL. In a first analysis, 210
      patients with solitary and multiple calculi without adjuvant measures before ESWL
      were studied. Of 210 patients, 141 (67%) were free from stones after 3 months).
      Significant influences on the success rate were body mass index and stone number.
      In a second analysis only those 160 patients with solitary calculi were
      considered. In this group, age, body mass index, stone location, stone burden and
      serum calcium significantly influenced the prognosis. When patients with adjuvant
      measures were added to the analysis an increasing prognostic importance of the
      stone burden was seen. In patients with a small to medium stone burden (< 4.0
      cm3), the number of stones seemed to be more important than the stone burden.
      Patients appear to have the best chance for successful ESWL when their body mass
      index is between 20 and 28, their age is between 40 and 60 years, their stones
      are in the renal pelvis and solitary, the stone burden is < 1.0 cm3, and when
      their serum calcium is normal.

PMID- 8137848
TI  - Protection of the right ventricular myocardium during acute right heart failure
      from pulmonary hypertension.
AB  - Protection of the failing right ventricle (RV) in the surgical treatment of
      massive pulmonary embolism is a keystone for myocardial recovery. This study
      evaluated whether cardioplegia should be used or avoided. In a modified
      Langendorff rat heart model pulmonary embolism was simulated by afterload
      elevation (20 cm H2O) for 30 min. Hearts were arrested with cardioplegic
      solutions [St. Thomas Hospital (ST); University of Wisconsin (UW); oxygenated
      Krebs-Henseleit-Potassium (KHP)] and stored for 10 min or were allowed to beat
      empty (NoCP) for 15 min. After reestablishing of baseline conditions groups were
      measured for 60 min. Cardiac index (CI) decreased in all groups to 20% during
      afterload elevation. Group NoCP showed 68 and Group ST 65% recovery after 10 min
      and deteriorated after 30 min. After 60 min CI was 37 (ST) and 39% (NoCP). UW and
      KHP showed a significantly better recovery (KHP 100%; UW 88%). At 60 min CI
      decreased to 60 (KHP) and 64% (UW), but was still significantly higher than
      corresponding values of NoCP and ST. Following increased pulmonary afterload
      cardioplegia with UW or KHP solution is beneficial for RV recovery. The
      composition of the cardioplegia is obviously important and needs further study.

PMID- 8137850
TI  - Extracorporeal shock wave lithotripsy monotherapy for staghorn calculi.
AB  - Forty-eight patients with large renal staghorn calculi of more than 35 mm in
      maximum length on plain X-rays were treated by extracorporeal shock wave
      lithotripsy (ESWL) monotherapy for a period of 2 years. Thirty patients, with a
      follow-up of more than 6 months after the last treatment, were included in this
      study. The surface area of the calculi was 1,290 mm2 on average. Based on plain X
      rays, 9 cases (30%) became free of calculi while 12 patients (40%) had a small
      amount of residual fragments (less than 100 mm2 in area). Adding these cases to
      those in which all the residual calculi were eliminated, the total turned out to
      be 21 cases (70%) and the treatment of staghorn calculi with ESWL was thus
      considered to have been fairly effective in the present series. The remaining 9
      cases (30%) contained a considerable amount of residuals (more than 100 mm2). The
      present study in the ESWL of large staghorn calculi revealed no clear
      relationship between the surface area of the stones and evacuation of the
      fragments. The amount of the residual fragments was significantly small when
      either the renal collecting system was less than 2,000 mm2 in area (p < 0.05), or
      when the ureteropelvic junction (UPJ) was equal or greater than 5 mm in diameter
      (p < 0.02) according to intravenous pyelography (IVP) before treatment. The
      complications associated with this treatment were minimal, with a high fever in
      only 3 patients that were treated easily by antibiotic therapy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8137851
TI  - Management of 53 cases of testicular trauma.
AB  - Fifty-three patients with testicular injury were investigated. Four (8%) had
      bilateral testicular injury and 15 (28%) had associated injuries, such as penile,
      spermatic cord, epididymal disruption, thigh, urethral, perineal skin avulsion,
      femoral vessel disruption and axillary venous injury. The mode of testicle trauma
      was blunt in 36 (63%) and penetrating in 21 (37%) cases. Early exploration was
      done in 43 (81%) patients including 4 with bilateral testicular injury: hematoma
      evacuation in 23 (49%), partial orchiectomy in 16 (34%) and total orchiectomy in
      8 (17%) cases, respectively. Otherwise, delayed exploration, due to the late
      presentation of more than 3 days after trauma, was done in the remaining 10 (19%)
      patients: hematoma evacuation in 6 (60%) and partial orchiectomy in 4 (40%)
      cases. The testicle salvage rate was 49/57 (86%), depending on the nature of
      testicular trauma. Hospitalization for uncomplicated cases was 4.82 +/- 1.85
      days, with prolongation to 10.79 +/- 3.64 days (p < 0.05) for patients having
      associated injuries. Exploration is advocated in all cases of hematocele,
      irrespective of testicle contusion or rupture. As minimal, the blood-clot from
      the tunica vaginalis sac should be evacuated, which would relieve disability and
      hasten recovery.

PMID- 8137852
TI  - Penile electromyography in the diagnosis of impotence.
AB  - Cavernous electromyography of the flaccid penis was done in 93 impotent patients
      that were evaluated with several types of electrodes. We found that the
      potentials are generated by the cavernous tissue and are not the reflections of
      distant electromyographic events. Using monopolar needle electrodes, accurate
      interpretation of the electromyographic tracings seems possible. Our results
      confirm the value of penile electromyography as a way to objectivate penile
      smooth muscle atrophy as well as pelvic autonomic neuropathy with subsequent
      penile smooth muscle desynchronization. A neuromuscular dysfunction may be the
      causative factor in 39% of our impotent patients.

PMID- 8137853
TI  - Urinary levels of N-acetyl-beta-D-glucosaminidase: a simple marker for predicting
      tubular damage in higher grades of vesicoureteric reflux.
AB  - We examined urinary N-acetyl-beta-D-glucosaminidase (NAG) levels in 84 children
      with grade III to grade V primary vesicoureteric reflux and in 31 controls. Age
      and sex of patients were similar in controls and patients and none had evidence
      of urinary infection at the time of testing. The mean urinary NAG activity levels
      in non-refluxing controls was 4.98 IU/g Cr, standard error (SE) 0.756. The mean
      urinary NAG activity levels in grade III patients (n = 43) was 6.024 IU/g Cr (SE
      0.898), in grade IV (n = 28) 9.059 IU/g Cr (SE 1.317), and in grade V (n = 13)
      17.298 IU/g Cr (SE 5.124). In this study, only patients with grade IV and V
      vesicoureteric reflux demonstrated significantly elevated NAG levels and within
      these grades of reflux, high NAG activity was confined to those patients who had
      associated renal scarring. NAG estimation in these patients with reflux
      nephropathy may be a useful simple additional test to assess tubular damage.

PMID- 8137854
TI  - Tumor-forming eosinophilic cystitis in children. Case report and review of
      literature.
AB  - Eosinophilic cystitis is an unusual bladder lesion of unclear etiology first
      described in 1960. It usually causes irritative voiding symptoms and hematuria
      and in its rare tumor-like appearance the disease may mimic an invasive bladder
      neoplasm. In the report herein, a case of an 11-year-old boy with a tumor-forming
      eosinophilic cystitis is presented which was mistaken for an infiltrative vesical
      malignancy until the histopathological study was completed. The principal
      clinical findings, differential diagnosis, etiology, pathogenesis and treatment
      modalities of this inflammatory disease are discussed.

PMID- 8137855
TI  - Computerized measurement of penile elastic fibres in potent and impotent men.
AB  - Intracavernous elastic fibres may play a role in human erectile tissue compliance
      and elasticity. Using computerized image analysis we have measured objectively
      the percentage of elastic fibres in corpus cavernosum tissues in both potent and
      impotent men. Twenty-two penile biopsies were performed in 5 potent and 17
      impotent patients due to vascular disease. The mean percentage of elastic fibres
      was 9% in normal patients. In 12 patients with venous leakage a significant
      decrease in the amount of elastic fibres of 5.1% was observed and in 5 patients
      with arterial disease it was 4.3%. No correlation between the reduction of the
      elastic fibre quantification and age was observed. Change in elastic fibre
      content may alter the relaxation properties of cavernosal tissue and play a role
      in the development of erectile dysfunction.

PMID- 8137856
TI  - Muscular cavernous single cell analysis in patients with venoocclusive
      dysfunction.
AB  - Enzymatically isolated smooth muscle cells of the corpora cavernosa obtained from
      open biopsies of 15 patients, clinically nonresponding to papaverine/phentolamine
      and prostaglandin E1 (PGE1) and classified by cavernosometry, were examined using
      the patch-clamp technique in the whole-cell configuration mode simultaneously
      monitoring the intracellular calcium concentration by means of the Ca(2+)
      sensitive fluorescence dye FURA-II. It could be demonstrated that extracellularly
      applied PGE1 induces smooth muscle relaxation by inhibition of voltage-dependent
      L-type Ca2+ currents (58 +/- 8%). Compared to intact cavenous tissue (n = 5), the
      smooth muscle cells of 14/15 PGE1 nonresponders had no evidence of functional
      disturbance. Due to intact smooth muscle cells in most cases, etiology of
      venoocclusive dysfunction remains unclear.

PMID- 8137857
TI  - Phenotypic and functional analysis of tumour-infiltrating lymphocytes from
      patients with renal cell carcinoma.
AB  - Twenty renal cell carcinomas were cultured in the presence of 200 IU/ml of
      recombinant interleukin-2; tumour-infiltrating lymphocytes (TIL) developed in 70%
      of cases; the phenotypic profile was heterogeneous in 11 TIL tested on day 30: 4
      were mostly CD8 positive, 4 mostly CD4 and 3 showed CD4-CD8-CD56 mixed
      phenotypes. The cytotoxic activity was also heterogeneous, and no TIL developed a
      tumour-specific cytotoxic activity. The phenotypic profile and cytotoxic activity
      were also tested after thawing, and this study demonstrated that TIL can be
      frozen at the time of the nephrectomy, then thawed and cultured for the purposes
      of therapeutic trials when metastases appear. The differences between TIL derived
      from renal cell carcinoma and TI1 derived from melanoma are discussed.

PMID- 8137858
TI  - Immunohistochemical studies on the expression of HLA class I antigens in renal
      cell carcinoma: comparison of primary and metastatic tumor tissue.
AB  - HLA class I expression was studied in 43 specimens of normal renal tissue, 48
      primary renal cell carcinomas (RCCs), and 12 metastases by immunofluorescence,
      using two different monoclonal antibodies (MoAbs; IOT2c, W6/32). Homogenous
      staining of all normal renal tissues was observed, as expected. From the panel of
      48 renal tumors, 40 had a strong expression of HLA class I antigens when tested
      with both MoAbs, 7 tumors had only weak expression of HLA class I and were
      regarded as 'HLA class I negative', and 1 tumor showed homogenous staining when
      tested with one MoAb (IOT2c) but was negative when the other was used (W6/32).
      This was the only case in which different results with the two MoAbs were found.
      Reduced expression of HLA class I antigens was observed in 5/12 metastases, and
      in 1 metastasis no expression of HLA class I could be seen. The staining
      chartacteristics of 10 metastases in comparison with the respective primary
      tumors were as follows: same HLA class I score 7/10; loss of HLA class I 3/10;
      gain of HLA class I 0/10. In RCC, a complete loss of HLA class I expression is a
      rare phenomena, which was observed in 0/48 primary tumors and in 1/12 metastases.
      Reduced expression of HLA class I antigens occurs in about 15% of primary tumors
      but is more frequent (50%) in metastases; however, if this is relevant for
      cytotoxicity by T lymphocytes is unknown.

PMID- 8137859
TI  - Effect of alpha-interferon alone and combined with other antineoplastic agents on
      renal cell carcinoma determined by the tetrazolium microculture assay.
AB  - The antiproliferative effect of various alpha-interferons (alpha-IFNs), alone or
      combined with other agents, on a renal cell carcinoma cell line was evaluated by
      the tetrazolium microculture assay to examine the rationale for combination
      therapies. Cells incubated in 96-week microculture plates at 5 x 10(3)/well were
      exposed to various agents for 3 days. There were no obvious differences in the
      growth inhibition caused by the 5 kinds of alpha-IFN examined as single agents.
      The combination of alpha-IFN with the following agents was also assessed: 5
      fluorouracil (5FU), methotrexate (MTX), mitomycin C, bleomycin, cis
      diaminedichloroplatinum (CDDP), vinblastine, etoposide (ETOP), alpha-IFN, tumor
      necrosis factor-alpha (TNF), and alpha-difluoromethylornithine. Synergism was
      observed for the combination of alpha-IFN+TNF, while the other combinations had
      additive or subadditive effects. No interference or antagonism was found.
      Trimodal combinations of alpha-IFN+MTX with either 5FU, ETOP, or CDDP all showed
      subadditive effects. These results indicated that an increased antiproliferative
      effect, although not necessarily synergistic, was obtained by the combination of
      alpha-IFN with a variety of antineoplastic agents, providing a rationale to seek
      for combination therapies including alpha-IFN for treating renal cell carcinoma.

PMID- 8137860
TI  - Secondary psoas abscess twenty-seven years after nephrectomy.
AB  - Abscesses of the psoas muscle are due to a hematogenous dissemination, to the
      spread of infection from adjacent intestinal structures, to osteomyelitis of the
      spine or to tuberculous infection of a disc space. In contrast, psoas abscesses
      related to the urological tract have only been described on exception. The
      present report focuses on a right psoas abscess which developed 27 years after a
      nephrectomy. The infectious process resulted from the spread of an acute vesical
      infection through the residual ureter. Analysis of 4 other cases reported in the
      literature allows us to delineate the clinical features of psoas abscesses of
      urological origin.

PMID- 8137861
TI  - Symptomatic heterotopic splenic tissue in the left renal fossa.
AB  - Renal fossa heterotopic splenic tissue is characteristically asymptomatic and is
      usually an incidental finding that has been reported to mimic renal or adrenal
      tumors. However, symptoms related directly to the splenic tissue do occur. We
      present an unique case with simultaneous occurrence of an accessory spleen and
      splenosis which were diagnosed following intentional radiological investigations
      conducted to evaluate flank pain which was probably related to the presence of
      the heterotopic spleens. CT complemented by isotopic liver-spleen scan is the
      radiological modality of choice in the diagnosis of renal fossa splenosis.
      However, MRI may significantly contribute to the evaluation by accurate
      delineation of blood supply and surgical separation planes.

PMID- 8137862
TI  - Gastrocystoplasty in children.
AB  - The use of stomach for bladder reconstruction is an important tool for the
      urologic surgeon. Just as one would not perform hypospadias repair knowing only
      one technique, one should not consider bladder reconstruction with only one
      option for augmentation available. The advantages, disadvantages and a brief
      overview of our operative technique are presented. We have been very pleased with
      our experience with the use of stomach in the appropriate clinical situation.

PMID- 8137863
TI  - Clinical experience with the Kaye nephrostomy tamponade catheter.
AB  - Herein, we report our clinical experience with achieving intraoperative
      hemostasis with the Kaye nephrostomy tamponade catheter. Since June 1990 this
      device has been used 10 times in 7 patients at our institution; in each patient
      immediate hemostasis of the nephrostomy tract was achieved.

PMID- 8137864
TI  - NE-100, a novel potent sigma ligand, preferentially binds to sigma 1 binding
      sites in guinea pig brain.
AB  - The selectivity of N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine
      monohydrochloride (NE-100) for sigma 1 and sigma 2 binding sites was studied by
      means of binding of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine ([3H]DTG)
      in guinea pig brain. NE-100 inhibited [3H](+)-pentazocine binding to sigma 1
      binding sites potently with an IC50 value of 1.54 +/- 0.26 nM while it had a weak
      effect on [3H]DTG binding to sigma 2 binding sites. The inhibitory effect of NE
      100 on [3H](+)-pentazocine was 55 times more potent than that on [3H]DTG binding.
      These results suggest that NE-100 is a potent and selective ligand for sigma 1
      binding sites.

PMID- 8137865
TI  - Vasoinhibitory action of KT2-734, an antihypertensive agent, in isolated rat
      aorta.
AB  - In rat aorta, KT2-734 inhibited contractile responses to 5-hydroxytryptamine (5
      HT) and KCl. KT2-734 inhibited the relaxing effect of verapamil, but not
      nifedipine. Similarly, verapamil, but not nifedipine, inhibited the vasorelaxing
      effect of KT2-734. KT2-734 relaxation was inhibited by endothelium removal but
      not by atropine and propranolol. Methylene blue, a guanylyl cyclase inhibitor,
      and NG-monomethyl arginine also inhibited the relaxation both in the presence and
      absence of endothelium. In the absence of endothelium, KT2-734 potentiated the
      relaxation induced by L-arginine, nitroglycerin and isoproterenol. In addition, M
      & B 22,948, a cGMP phosphodiesterase inhibitor, and theophylline inhibited and
      potentiated, respectively, KT2-734-induced relaxation. However, methylene blue
      inhibited the potentiation of isoproterenol relaxation by KT2-734 and that of KT2
      734-relaxation by theophylline. KT2-734 caused increases in the level of cGMP
      without significantly affecting the cAMP level. These results suggest that KT2
      734 may cause endothelium-independent relaxation mainly due to inhibition of cGMP
      phosphodiesterase.

PMID- 8137866
TI  - Role of angiotensin AT1 receptor in the cardiovascular response to footshock.
AB  - This study assessed the effect of non-peptide angiotensin II receptor subtype
      antagonists on the cardiovascular response to footshock. Effects of electric
      stimulation (1, 2 or 5 Hz) on mean arterial pressure (MAP) and heart rate (HR)
      were determined. Peripheral or central administration of losartan, an angiotensin
      AT1 receptor antagonist (1 or 10 mg/kg s.c., or at 10, 30 or 100 micrograms/5
      microliters i.c.v.), inhibited the mean arterial pressure response but not the
      heart rate response to footshock. In contrast, the MAP response to exogenous
      administration of norepinephrine was not inhibited by subcutaneous administration
      of losartan (10 mg/kg). Given at 100 micrograms/5 microliters i.c.v., the
      angiotensin AT2-selective receptor antagonist, PD 123319, did not reduce
      hemodynamic responses to electric stimulation. These results suggest that, in
      acute stress, endogenous angiotensin II facilitation of noradrenergic
      transmission is mediated through the angiotensin AT1 receptor.

PMID- 8137867
TI  - ATP-sensitive K+ channel openers inhibit morphine withdrawal.
AB  - We studied the effects of two different ATP-sensitive K+ channel openers on
      naloxone-precipitated withdrawal in morphine-dependent mice. The i.c.v.
      administration of cromakalim and diazoxide (both at 5-40 micrograms/mouse) dose
      dependently inhibited several signs of morphine withdrawal (number of jumps and
      episodes of forepaw tremors, and body weight loss). At present it is impossible
      to specify the exact mechanism(s) involved in this effect. However, considering
      that morphine opens K+ channels in neurons, it is tempting to suggest that K+
      channel openers can mimic the effects of morphine on neuronal K+ currents, and as
      a consequence can act as substitutes for this drug during morphine withdrawal.

PMID- 8137868
TI  - Aldose reductase inhibition, Doppler flux and conduction in diabetic rat nerve.
AB  - Two chemically distinct aldose reductase inhibitors, ponalrestat and tolrestat,
      were tested against laser Doppler blood flow and conduction deficits in the
      sciatic nerve of diabetic rats. The effects of two months of streptozotocin
      induced diabetes and aldose reductase inhibition on body weight, plasma glucose,
      and nerve sugars and polyols were comparable to those reported previously. Nerve
      blood flow, reflected by laser Doppler flow measurements, and motor nerve
      conduction velocity were both significantly less in diabetic than in control
      animals. Both of these reductions were prevented by ponalrestat, but not
      tolrestat. Thus, either deficits in laser Doppler blood flow and conduction are
      not aldose reductase inhibitor-dependent or tolrestat has some other property
      which offsets the beneficial effects of aldose reductase inhibition. In either
      case, these data are consistent with the hypothesis that reduced nerve blood flow
      contributes to conduction deficits in diabetes.

PMID- 8137869
TI  - Selective activation of Ca(2+)-dependent K+ channels by novel benzimidazolone.
AB  - Activators and blockers of specific ion channels are important pharmacological
      tools for characterizing ion channels and their influence on cell function. The
      large-conductance Ca(2+)-dependent K+ channel (BK channel) is blocked by peptides
      such as charybdotoxin and iberiotoxin, but no selective activator of the channel
      has been described. Here we report single-channel and whole-cell patch-clamp
      experiments on the specific activation of BK channels in aortic smooth muscle
      cells with a new heterocyclic molecule, NS 1619 (1-(2'-hydroxy-5'
      trifluoromethylphenyl)-5-trifluoromethyl- 2(3H)benzimidazolone). The effect of NS
      1619 on the BK channel was dose-dependent, resulting in a shift of the activation
      curve by up to -50 mV towards negative membrane potentials. The effect was fully
      reversible and was antagonized by charybdotoxin as well as by tetraethylammonium
      ions. The compound hyperpolarized the smooth muscle cells. NS 1619 is a selective
      and new type of K+ channel activator, which may significantly modulate cell
      excitability.

PMID- 8137870
TI  - Potentiation by metal ions of ryanodine contracture of the mouse diaphragm.
AB  - The aim of this study was to elucidate the possible mechanism of the potentiating
      action of metal ions (Cu2+, Hg2+, Ag+ and SeO3(2-)) on the ryanodine-induced
      contracture of the mouse diaphragm. The ryanodine contracture in the quiescent
      muscle could be augmented by either electrical stimulation or pretreatment with
      high K+ of the diaphragm. Lowering the external Ca2+ concentration from 2.5 mM to
      1 microM or the addition of 7 microM d-tubocurarine, which abolished the muscle
      excitability by blocking the receptors of acetylcholine, markedly attenuated the
      ryanodine contracture. Application of Cu2+, Hg2+, Ag+ and SeO3(2-) but not Ni2+
      and Co2+, to quiescent muscle restored the ryanodine contracture. The
      potentiating effects of Hg2+, Ag+ and high K+ were dependent on the presence of
      external Ca2+ (2.5 mM) and intact transverse tubular systems but the effects of
      Cu2+ and SeO3(2-) were not. Treatment with 1 mM dithiothreitol 10 min after the
      application of metal ions and then subsequent addition of ryanodine abolished the
      potentiating effects of Hg2+ and Ag+ but not those of Cu2+ and SeO3(2-). Although
      ryanodine by itself had no effect on 45Ca2+ uptake by the mouse diaphragm, it
      significantly potentiated the increased 45Ca2+ uptake elicited by Cu2+ and Hg2+.
      Further elucidation of the interaction between metal ions and ryanodine on the
      outer sarcolemma showed that all of these metal ions, including the inactive Co2+
      and Ni2+, not only decreased the membrane potential but also altered the membrane
      input resistance, effects which were not correlated with the potentiating effects
      of the metal ions on the ryanodine contracture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137871
TI  - Effect of 21-aminosteroid lipid peroxidation inhibitor, U74006F, in the rat
      middle cerebral artery occlusion model.
AB  - The aim of this study was to evaluate the effect of 21-aminosteroid lipid
      peroxidation inhibitor, U74006F, on ischaemic brain tissue damage using the rat
      middle cerebral artery occlusion model. Under anaesthesia, the left middle
      cerebral artery was exposed without cutting the dura mater via a subtemporal
      craniotomy, under an operating microscope. Photo-illumination (wave length; 540
      nm) was applied to the middle cerebral artery and then rose bengal (20 mg/kg) was
      administered intravenously. The middle cerebral artery was completely occluded by
      thrombus about 6 min after the administration of rose bengal. U74006F (1.0 mg/kg)
      was then injected intravenously just after the cessation of illumination. Twenty
      four hours after the operation, the extent of ischaemic damage was measured by
      magnetic resonance imaging technique. After measuring the extent of ischaemic
      damage, the brain was immediately removed from animals treated with or without
      U74006F for determination of lipid peroxidation, and the generation of free
      arachidonic acid in the brain. U74006F significantly (P < 0.01) reduced the size
      of ischaemic damage. Twenty-four hours after the operation, lipid peroxidation
      and the concentration of free arachidonic acid in the left hemisphere (infarction
      side) were significantly (P < 0.05) higher than in the right hemisphere. U74006F
      significantly (P < 0.05) decreased the content of lipid peroxidation products and
      free arachidonic acid. There was a significant (P < 0.05) correlation between the
      extent of ischaemic damage and the concentration of lipid peroxidation products
      in the left hemisphere 24 h after the operation. In conclusion, U74006F might
      reduce the extent of ischaemic damage by inhibiting lipid peroxidation in the
      brain, thus minimizing oxidative damage to neural tissues.

PMID- 8137872
TI  - Developmental changes in the response of rat isolated duodenum to nicotine.
AB  - Developmental changes in the response to ganglionic stimulants, nicotine and
      dimethylphenylpiperazinium, were investigated in rat isolated duodenum by
      recording isotonic mechanical activity. The duodenal response to
      nicotine/dimethylphenylpiperazinium (3 x 10(-7) to 10(-3) M) in neonatal rats was
      contraction, which was blocked by hexamethonium, tetrodotoxin and hyoscine. The
      response to nicotine/dimethylphenylpiperazinium (10(-6) to 10(-4) M) in the adult
      duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but
      by neither guanethidine nor hyoscine. The transition of the response to
      nicotine/dimethylphenylpiperazinium from contraction to relaxation occurred at
      around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was
      significantly inhibited by preincubation with alpha-chymotrypsin, a proteolytic
      enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline,
      a P1 purinoceptor antagonist. Nicotine-induced relaxation was desensitized by
      alpha, beta-methylene ATP, a stable P2x purinoceptor agonist. These results
      suggest that the contractile response of isolated duodenum to nicotine is
      mediated through cholinergic transmission in neonatal rats and the relaxant
      response is mediated through non-adrenergic, non-cholinergic transmission, which
      involves both peptidergic and purinergic transmission, in adult rats.

PMID- 8137873
TI  - Pharmacological study of several effects of hydralazine in the bisected rat vas
      deferens.
AB  - We have studied several effects of hydralazine in the bisected rat vas deferens.
      Hydralazine produced a shift to the left of the concentration-response curve for
      noradrenaline, with potentiation of the maximal response in both portions of the
      vas deferens. In contrast it caused a shift to the right of the concentration
      response curve for noradrenaline in preparations pretreated with cocaine
      (inhibitor of catecholamine neuronal uptake), and of the curve for methoxamine
      and for CaCl2 (in depolarizing medium with K+ 55 mM), in all cases with
      depression of the maximal response. Hydralazine enhanced the contractions induced
      by noradrenaline in Ca(2+)-free medium, except in the presence of cocaine. It had
      no effect on [3H]noradrenaline neuronal uptake into noradrenergic neurons of the
      vas deferens, nor did it affect basal or K(+)-induced 45Ca2+ uptake. These
      results suggest that hydralazine potentiates the contractions elicited by
      noradrenaline by a mechanism other than blockade of the neuronal uptake of this
      catecholamine. Our results also suggest that the inhibition by hydralazine of the
      contractions elicited by Ca2+ (in Ca(2+)-free depolarizing high-K+ 55 mM
      solution) and by methoxamine is not due to an action on voltage-dependent Ca2+
      channels, but may reflect an intracellular site of action.

PMID- 8137874
TI  - Antiproliferative effect of baicalein, a flavonoid from a Chinese herb, on
      vascular smooth muscle cell.
AB  - The effects of baicalein, baicalin and wogonin, the flavonoids from Scutellaria
      baicalensis, on the proliferative responses of cultured rabbit vascular smooth
      muscle cells were studied. The proliferative response was determined from the
      uptake of tritiated thymidine. In rabbit vascular smooth muscle cells, all three
      flavonoids dose dependently inhibited the proliferative response induced by 5%
      fetal calf serum at the dose range of 10(-6) to 10(-4) M. Baicalin and wogonin
      were less effective than baicalein as inhibitors of the serum-induced smooth
      muscle cell proliferation, indicating that the three hydroxyl groups on positions
      5, 6 and 7 seem to be necessary and sufficient for full inhibitory activity
      against the proliferative response of smooth muscle cells. Baicalein had a
      greater inhibitory effect on the proliferative reponse stimulated by platelet
      derived growth factor than on serum-stimulated proliferation. Baicalein, a
      flavonoid with antiproliferative and lipoxygenase-inhibitory activities, may be
      useful as another template for the development of better drugs to prevent the
      pathological changes of atherosclerosis and restenosis.

PMID- 8137875
TI  - Antinociceptive effect of lipopolysaccharide from Pantoea agglomerans on
      streptozotocin-induced diabetic mice.
AB  - The antinociceptive effect of lipopolysaccharide from Pantoea agglomerans (LPSp)
      in streptozotocin-induced diabetic mice was examined. Although subcutaneous
      (s.c.) administration of LPSp produced a dose-dependent inhibition of the tail
      flick response in both non-diabetic and diabetic mice, the antinociceptive
      response was greater in diabetic mice than in non-diabetic mice. The
      antinociceptive effects of LPSp in both diabetic and non-diabetic mice were
      significantly antagonized by s.c. administration of naltrindole, a selective
      delta-opioid receptor antagonist or nor-binaltorphimine, a selective kappa-opioid
      receptor antagonist, but not by beta-funaltrexamine, a selective mu-opioid
      receptor antagonist. These results suggest that LPSp produces a marked
      antinociceptive effect in diabetic mice through the activation of delta- and
      kappa-opioid receptors.

PMID- 8137876
TI  - Differential effects of selective tachykinin NK2 receptor antagonists in rat
      spinal cord.
AB  - The effects of intrathecally (i.t.) injected selective tachykinin NK2 receptor
      antagonists, MEN 10,207, MEN 10,376 and R396, on the spinal effect of neurokinin
      A were studied in decerebrate, spinalized, unanesthetized rats. I.t. neurokinin A
      (7 pmol) briefly facilitated the flexor reflex, an effect that was dose
      dependently inhibited by pretreatment with MEN 10,207 and MEN 10,376 with similar
      and high potency. I.t. R396 itself caused strong facilitation of the flexor
      reflect. At lower doses, the effect of i.t. neurokinin A was potentiated by R396.
      R396 only exhibited moderate antagonism of neurokinin A-induced reflex
      facilitation even at very high doses. It has been proposed that the tachykinin
      NK2 receptor may be further classified into two subtypes, NK2A and NK2B, with MEN
      10,207 and MEN 10,376 having high affinity for the former and R396 for the
      latter. Our results suggested that the tachykinin NK2 receptor in rat spinal cord
      which mediates the excitatory effect of neurokinin A may belong to the NK2A
      subpopulation of receptors.

PMID- 8137877
TI  - Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through
      protein kinase C.
AB  - Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely
      dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with
      pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg
      interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in
      concentrations 25-fold higher than interleukin-1 beta) completely blocked the
      interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests
      that interleukin-1 beta action is through a specific interaction with an
      interleukin-1 membrane receptor site. The application of other cytokines and
      growth factors (interleukin-6, epidermal growth factor, and basic fibroblast
      growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect,
      indicating specificity of action of interleukin-1 beta. The depression of the
      Ca2+ channel current by interleukin-1 beta was prevented by the extracellular
      application of pertussis toxin, and by the intracellular application of GDP[beta
      S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12
      myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol
      ester-induced depression was not additive to that induced by interleukin-1 beta.
      These results suggest mediation of interleukin-1 beta action through a pertussis
      toxin-sensitive G-protein coupled interleukin-1 receptor associated with the
      activation of protein kinase C. The depression of the Ca2+ channel current by
      interleukin-1 beta may be involved in the regulation of neuronal excitability
      during pathological conditions and in the induction and/or progression of
      neurodegenerative processes.

PMID- 8137878
TI  - Analogues of tetramethylpyrazine affect membrane fluidity of liposomes:
      relationship to their biological activities.
AB  - Several structurally similar pyrazine derivatives, tetramethylpyrazine,
      triethylpyrazine and tetraethylpyrazine have previously been found to inhibit a
      broad spectrum of plasmalemma-associated biological activities of various
      tissues, including ion channels and membrane receptors in a given order of
      potency that increases with increasing bulkiness and hydrophobicity of these
      drugs. Our earlier speculation that the multiple membrane effects elicited by
      these pyrazine derivatives were associated with changes in the bulk physical
      properties of the biological membranes in the presence of these drugs was
      confirmed by fluorescence polarization and electron spin resonance studies. Since
      biological membranes contain a complicated mixture of a large variety of lipids
      and proteins, we chose to study the molecular properties of the interaction of
      these three pyrazine derivatives using a simple model system composed of
      synthetic phospholipids. We measured the effects of the drugs on the fluidity (or
      microviscosity) of these model membranes, as well as determining the phase
      transition properties of the model membranes with the use of fluorescence
      polarization, electron spin resonance and differential scanning calorimetry. All
      the methods employed yielded qualitatively similar results. Tetramethylpyrazine,
      the smallest and the least hydrophobic amongst these three drugs, had minimal or
      no effect on the phase-transition of phospholipids based on temperature
      dependence studies, whereas tetraethylpyrazine, the largest and the most
      hydrophobic of the three, elicited the most potent effect in a concentration
      dependent manner. These results could be attributed to the amount of
      incorporation of these pyrazine derivative into the liposomes, an interaction
      which occurs more favourably at temperatures above the gel to liquid crystalline
      phase-transition temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8137879
TI  - Inhibitory effects of botulinum toxin on 5-HT1C receptor-induced Cl- current in
      Xenopus oocytes.
AB  - Several low molecular weight G proteins have been identified, but their
      functional roles remain unclear. To clarify the involvement of low molecular
      weight G protein in receptor-stimulated turnover of polyphosphoinositide (PI)
      turnover, influences of botulinum toxins on serotonin (5-HT)-stimulated Cl-
      current mediated by PI turnover were investigated using Xenopus oocytes injected
      with rat brain mRNA. Treatment with botulinum toxin C, D or purified ADP
      ribosyltransferase of botulinum toxin (botulinum toxin C3 enzyme) inhibited the 5
      HT-induced Cl- current in oocytes, and ADP-ribosylated 23 kDa proteins. Both
      botulinum toxin C3 enzyme-induced inhibition of the current and ADP-ribosylation
      were suppressed by pretreatment with antibotulinum toxin C3 enzyme antibody.
      Botulinum toxin D treatment of oocytes was ineffective in the response of Cl-
      current induced by injection of 50 pmol inositol 1,4,5-trisphosphate and 50 pmol
      Ca2+. It is suggested that low molecular weight G proteins ADP-ribosylated by
      botulinum toxin C3 enzyme are involved in phospholipase C activation in Xenopus
      oocytes.

PMID- 8137880
TI  - Human brain imidazoline receptors: further characterization with [3H]clonidine.
AB  - The aim of the present study was to further characterize [3H]clonidine binding in
      the ventrolateral medulla of the human brainstem, the region involved in the
      vasodepressor effect of imidazoline drugs of the clonidine type. Under basal
      conditions, [3H]clonidine can bind both to the imidazoline receptors and to the
      alpha-adrenoceptors. The latter represent only a small part of the total
      [3H]clonidine binding with a Bmax of 61 +/- 13 fmol/mg proteins and a KD of 4.9
      +/- 2.2 nM. Most of the binding was associated with imidazoline receptors with a
      KD of 67 +/- 13 nM and a Bmax of 677 +/- 136 fmol/mg protein. alpha-Adrenoceptor
      binding of [3H]clonidine could be completely prevented when membranes were either
      treated during preparation with the aIkylating agent phenoxybenzamine or
      incubated in the presence of 30 microM (-)-noradrenaline or in the presence of
      the non-hydrolysable analogue of GTP, guanylyl imidodiphosphate (Gpp(NH)p). When
      the alpha-adrenoceptors binding was prevented, we demonstrated the insensitivity
      of [3H]clonidine binding to Gpp(NH)p and showed that the competition between
      clonidine and idazoxan for imidazoline receptors was insensitive to Gpp(NH)p
      suggesting that imidazoline receptors are not G protein coupled receptors. The
      specificity of [3H]cloniding binding to imidazoline receptors in the human
      ventrolateral medulla indicates that these receptors are different from imidazole
      receptors as defined with p-aminoclonidine in the bovine brainstem.

PMID- 8137881
TI  - In vivo recovery of alpha 1-adrenoceptors in rat myocardial tissue after
      alkylation with phenoxybenzamine.
AB  - The rate of recovery of rat myocardial alpha 1-adrenoceptor density and
      responsiveness after in vivo block with phenoxybenzamine (1 mg/kg, i.p.) have
      been investigated by measuring [3H]prazosin binding, and noradrenaline-stimulated
      [3H]inositol phosphate production. Repopulation of alpha 1-adrenoceptors was
      monoexponential, with a t1/2 of 33 h; functional recovery was also
      monoexponential, with t1/2 of 28 h. Furthermore, our results clearly demonstrate
      the absence of a receptor reserve for alpha 1-adrenoceptors mediating
      noradrenaline-stimulated phosphoinositide breakdown in rat myocardial tissue.
      These observations indicate a close relationship between the density of
      [3H]prazosin binding sites and the ability of alpha 1-adrenoceptors to respond to
      noradrenaline. Moreover, based on competition curves for inhibition of specific
      [3H]prazosin by WB-4101 to rat myocardial membranes 48 h and 7 days after the
      administration of phenoxybenzamine, the results suggest that rat myocardial
      membranes contain both alpha 1-adrenoceptors subtypes, i.e., alpha 1A and alpha
      1B, in an approximate ratio of 20:80, and this relative ratio does not seem to be
      altered during the recovery process.

PMID- 8137882
TI  - Polyamines modulate [3H]L-689,560 binding to the glycine site of the NMDA
      receptor from rat brain.
AB  - The N-methyl-D-aspartate (NMDA) receptor complex possesses distinct recognition
      sites for glutamate, glycine and polyamines, which appear to be allosterically
      linked. We have investigated the effects of polyamines on the binding of the
      glycine site antagonist [3H](+/-)-4-(trans)-2-carboxy-5,7-dichloro-4
      phenylaminocarbonylamino - 1,2,3,4-tetrahydroquinoline ([3H]L-689,560), using rat
      cortex/hippocampus P2 membranes. Spermine and spermidine partially inhibited
      [3H]L-689,560 binding under non-equilibrium conditions, with IC50 values of 25.9
      and 106 microM, respectively. The putative polyamine site antagonists arcaine,
      1,10-diaminodecane, diethylenetriamine and putrescine had no effect on [3H]L
      689,560 binding per se at 1 mM. The inhibition of [3H]L-689,560 binding by
      spermine was antagonised by arcaine in a competitive manner, but not by 1,10
      diaminodecane, diethylenetriamine or putrescine. Kinetic analysis revealed that
      spermine (100 microM) decreased the association and dissociation rates of [3H]L
      689,560 binding. In saturation experiments 100 microM spermine increased the KD
      for [3H]L-689,560 binding from 1.99 nM to 4.03 nM, with no effect on the number
      of binding sites. Spermine increased the affinity of glycine site agonists in
      displacing [3H]L-689,560 binding, with no effect on inhibition by partial
      agonists or antagonists, suggesting that spermine promotes an 'agonist
      preferring' state. Modulation of [3H]L-689,560 binding by agonists for the
      polyamine and glutamate sites on the NMDA receptor did not appear to be additive
      in nature.

PMID- 8137884
TI  - Nucleoside transport inhibition and platelet aggregation in human blood: R75231
      and its enantiomers, draflazine and R88016.
AB  - In this study, we determined whether R75231, (+/-)-2-(aminocarbonyl)-N-(4-amino
      2,6-dichlorophenyl)-4-[5,5-bis( 4-fluoro- phenyl)pentyl]-1-piperazineacetamide,
      and its two enantiomers, all nucleoside transport inhibitors, could play a role
      as anti-aggregatory agents. First, we determined the binding characteristics of
      [3H]nitrobenzylthioinosine, also a nucleoside transport inhibitor, on intact
      human erythrocytes. The Kd value was 0.27 +/- 0.04 nM and the Bmax was 23.5 +/-
      5.1 pmol/10(9) erythrocytes. Second, we studied the ability of R75231 and its
      enantiomers R88021 ((-)-R75231, or draflazine) and R88016 ((+)-R75231), to
      displace [3H]nitrobenzylthioinosine. R75231 had an IC50 value of 2.2 +/- 0.3 nM.
      R88021 was twice as potent as R75231 and R88016 was approximately 20-fold less
      potent than R75231. Finally, the ability of these nucleoside transport inhibitors
      to enhance anti-aggregatory effects of adenosine was examined in whole human
      blood. Adenosine alone, 10 microM, had no effect on ADP-induced platelet
      aggregation. However, in the presence of 1 microM R75231, 10 microM of adenosine
      inhibited the aggregatory response completely. Dose-response curves indicated
      that the IC50 values of draflazine and R88016 were approximately 0.5 microM and
      10 microM, respectively. R75231 and its enantiomers are valuable research tools
      to assess the role of the nucleoside transporter. Moreover, R75231 and draflazine
      (R88021) may prove to be useful as anti-aggregatory agents.

PMID- 8137883
TI  - Localization of [125I]SAP-N3 binding in the human platelet thromboxane
      A2/prostaglandin H2 receptor by proteolytic cleavage analysis.
AB  - Photo-affinity labeling studies of purified human platelet thromboxane
      A2/prostaglandin H2 receptor by the ligand 7-[(1R,2S,3S,5R)-6,6-dimethyl-3-(4
      azido-3- iodobenzenesulfonylamino)bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid
      ([125I]SAP-N3) combined with proteolytic cleavage studies were performed to
      initiate studies aimed at localizing the binding domain of this ligand. Two
      endoproteinases, endoproteinase Asp-N (Asp-N) and endoproteinase Lys-C (Lys-C),
      and the endoglycosidase, N-glycosidase F (endo-F), were employed to generate
      fragments for analysis by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) autoradiography. Computational analysis of the
      published sequence was then employed to predict cleavage products and then
      compared to the observed digestion results. Results of this work suggest that the
      majority of the binding domain of [125I]SAP-N3 includes putative transmembrane
      regions M-3 and M-4 (amino acids 99-192) with a minor component at the amino and
      carboxyl terminus.

PMID- 8137885
TI  - NMDA receptor-mediated stimulation of rat cerebellar nitric oxide formation is
      modulated by cyclic AMP.
AB  - The effect of intracellular cyclic AMP (cAMP) on N-methyl-D-aspartate (NMDA)
      receptor-mediated stimulation of nitric oxide (NO) formation was investigated in
      rat cerebellar slices. Forskolin (30-120 microM), while lacking any direct effect
      on NO production, elicited a concentration-dependent enhancement of the response
      to 10 microM NMDA. Dideoxyforskolin, which does not activate adenylyl cyclase did
      not influence the NMDA response. Increasing intracellular cAMP directly by
      incubation with the membrane-permeant analogue of cAMP, 2'-o-dibutyryladenosine
      3'5'-cyclic monophosphate (dibutyryl cAMP) (1 mM), similarly enhanced NO
      formation, as did prevention of cAMP degradation with the phosphodiesterase
      inhibitor theophylline. The enhancement of NMDA activity appeared to involve
      protein phosphorylation (possibly of the receptor itself) since the protein
      kinase A inhibitor H-89, abolished the enhancements with both forskolin and
      dibutyryl cAMP. Thus cAMP may have a physiological role in the modulation of NMDA
      receptor-stimulated synthesis of NO.

PMID- 8137886
TI  - Effect of CH3HgCl and several transition metals on the dopamine neuronal carrier;
      peculiar behaviour of Zn2+.
AB  - CH3Hg+ and metal ions inhibited the specific binding of (1-[2
      (diphenylmethoxy)ethyl]-4-(3-phenyl-2-[1-3H]propenyl) piperazine) ([3H]GBR 12783)
      to the dopamine neuronal carrier present in membranes from rat striatum with a
      general rank order of potency CH3Hg+ > Cu2+ > Cd2+ > Zn2+ > Ni2+ = Mn2+ = Co2+,
      suggesting that -SH groups are chiefly involved in this inhibition. Five
      millimolar dithiothreitol reversed the rather stable block of the specific
      binding produced by Cd2+ or Zn2+. An increase in the concentration of Na+, or
      addition of either K+ or Ca2+ reduced the inhibitory effects of metal cations,
      except Cu2+. Zn2+ (3 microM) reduced the inhibitory potency of Cd2+ on the
      binding but was ineffective against CH3Hg+ and Cu2+. Zn2+ at 0.3 to 10 microM
      significantly enhanced the specific binding of [3H]GBR 12783 and [3H]cocaine by
      42 to 146%. Zn2+ (3 microM) increased the affinity of all pure uptake inhibitors
      tested and of the majority of the substrates for the [3H]GBR 12783 binding site.
      Dissociation experiments revealed that Zn2+ both inhibited and enhanced the
      [3H]GBR 12783 binding by recognizing amino acids located close to or in the
      radioligand binding site. Micromolar concentrations of Zn2+ noncompetitively
      blocked the [3H]dopamine uptake but they did not modify the block of the
      transport provoked by pure uptake inhibitors. These findings suggest that Na+,
      K+, Ca2+ and metal ions could recognize some -SH groups located in the [3H]GBR
      12783 binding site; low concentrations of Zn2+ could allow a protection of these 
      SH groups.

PMID- 8137887
TI  - Expression of interleukin-1 alpha and beta in early passage fibroblasts from
      aging individuals.
AB  - Human diploid fibroblasts (HDFs) from newborn foreskin constitutively express
      interleukin-1 (IL-1) mRNA and protein after completing at least 70%
      (approximately 40 population doublings) of their in vitro life span. This IL-1 in
      turn induces the synthesis of specific proteins in aging HDFs. To determine
      whether IL-1 expression may be promoted by in vivo aging, we analyzed the
      expression of IL-1 and of inducible mRNAs in HDFs from two normal individuals 55
      and 92 years old and in HDFs from a patient with premature aging caused by
      Werner's syndrome. By reverse transcription polymerase chain reaction (RT-PCR)
      and enzyme-linked immunosorbent assay (ELISA), we detected expression of IL-1
      alpha and beta mRNA and protein in early passage HDFs from both normal
      individuals and the Werner's syndrome patient. These HDFs also expressed the IL-1
      inducible mRNAs for stromelysin, plasminogen activator inhibitor type 2,
      manganous superoxide dismutase, and collagenase. These results suggest that an
      age-dependent expression of IL-1 occurs either in vivo or after a few cell
      divisions in vitro. Therefore, the fibroblast phenotype is modified by the
      expression of IL-1-inducible genes during aging.

PMID- 8137889
TI  - Adult life span as a function of age at maturity.
AB  - A regression analysis was made of age at first reproduction in female mammals, as
      a function of body weight, using the data of Wootton. Data on maximal life span,
      also expressed as a function of body weight, were used to calculate "adult" life
      span, wherever possible, by subtracting the cognate value for age at first
      reproduction. Then a regression analysis of adult life span as a function of age
      at first reproduction was made. In both cases global regression lines (i.e., for
      whole data sets) were computed by standard least squares and by a robust method,
      as well as local regression lines for subgroups classified by taxonomic and
      ecological criteria. The slopes of the various regression lines were found to
      vary widely as a function of the method of classification. This result argues
      against the notion that the ratio of life history variables is a constant, or
      that one life history variable is likely to be a simple function of another. The
      results for bats are anomalous, in that age at first reproduction appears to be
      independent of body weight (over about two orders of magnitude). It is concluded
      that a full understanding of life history variables, such as maximal life span
      and age at maturity, is likely to depend on combined physiological, ecological,
      and evolutionary insights.

PMID- 8137888
TI  - Influences of aging and dietary restriction on red blood cell density profiles
      and antioxidant enzyme activities in rhesus monkeys.
AB  - Dietary restriction (DR) retards aging processes in rodents and other animals but
      its influence on aging in primates is unknown. In rats, the average density of
      red blood cells (RBCs) reportedly increases with RBC age and decreases with host
      age and RBC antioxidant enzyme activities fall with both types of aging. We
      determined RBC density profiles and antioxidant enzyme activities in four groups
      (n = 5) of male rhesus monkeys. The "Control" group (11-14 years) was fed a
      purified diet ad lib and the "DR" group (11-16 years) were fed 70% of the ad lib
      level for two years. "Young" (6-10 years) and "Old" (27-36 years) monkeys were
      fed a nonpurified diet ad lib. The average RBC size was least in the most dense
      fraction (F4) and internal structural complexity increased with RBC density based
      on flow cytometry analysis but these were not influenced by host age or DR.
      Catalase activity decreased with increasing density. In contrast to findings in
      rats, age and fraction differences in glutathione peroxidase activities were
      insignificant. DR did not influence enzyme activities. These data suggest that
      aging in rhesus monkeys influences RBC density profiles and antioxidant enzyme
      activities far less strikingly than has been reported in rats.

PMID- 8137890
TI  - A cluster analysis study of acetyl-L-carnitine effect on NMDA receptors in aging.
AB  - Aging is associated with a reduction in the maximum density of n-methyl-d
      aspartate (NMDA)-sensitive glutamate binding sites in the hippocampus of Fischer
      344 rats. This study was designed to investigate the effect of acetyl-l-carnitine
      (ALCAR) on NMDA receptors in the old rat (24 months) after chronic or single-dose
      treatments. The number of NMDA receptors was significantly decreased in the old
      rat hippocampus by 19.5% compared with the young rat. A six-month treatment with
      ALCAR in the old rat attenuated the loss of NMDA binding sites in the
      hippocampus. A single-dose treatment with ALCAR in the old rat increased the Bmax
      value by 35%, while no change was observed in the young group. We conclude that
      ALCAR can exert two actions: a trophic/neuro-preserving one when chronically
      administered during aging, and a stimulatory one when given at a single dose in
      the aged rat.

PMID- 8137891
TI  - Alterations in CD8+ cell distribution in gut-associated lymphoid tissues (GALT)
      of the aging Fischer 344 rat: a correlated immunohistochemical and flow
      cytometric analysis.
AB  - The distribution of CD8+ phenotype (cytotoxic/suppressor) T lymphocytes in
      Peyer's patches and intestinal lamina propria in young adult (3-6 months) and old
      (24-29 months) Fischer 344 rats was examined using immunohistochemical and flow
      cytometric analyses. Flow cytometric analysis confirmed previous reports
      indicating no change with age in the proportion of Peyer's patch CD8+ cells in
      the rat. Immunohistochemical analysis showed discrete zones of densely stained
      CD8+ cells in the interfollicular areas and weakly stained cells within the
      follicles in Peyer's patches in young adult animals. In old rats, the number of
      intensely stained CD8+ cells between the follicles was markedly reduced and
      positively stained cells were distributed throughout the Peyer's patches. In
      addition, the population density of CD8+ cells is more diffuse in old animals,
      the number of CD8+ lymphocytes in the intestinal lamina propria increased 2.5
      fold with aging from 533 +/- 59 cells/mm2 in young adult to 1312 +/- 83 cells/mm2
      in old rats. The findings suggest that CD8+ cell distribution in the inductive
      and effector sites of gut associated lymphoid tissue undergoes age-related
      shifts.

PMID- 8137892
TI  - Effects of aging on ribosomal protein L7 messenger RNA levels in cultured rat
      preadipocytes.
AB  - Ribosomal protein L7 mRNA is a cell cycle-independent message whose levels are
      lower in late passage "senescent" fibroblasts than early passage cultures. To
      determine whether decreases in L7 mRNA levels also occur during aging in tissues
      in vivo and whether reduced L7 mRNA is caused by terminal differentiation, we
      measured L7 and adipsin (a differentiation-dependent serine protease) mRNA levels
      in undifferentiated and differentiated preadipocytes and glyceraldehyde-3
      phosphate dehydrogenase mRNA in differentiated preadipocytes cultured from
      perirenal fat depots of 3-, 17-, and 24-month-old male rats. L7 mRNA levels
      decreased with increasing age and were not affected by differentiation. In the
      same cultures, adipsin mRNA levels did not increase with age but did increase
      with differentiation, confirming that the preadipocytes exposed to enriched
      medium had, in fact, differentiated. Glyceraldehyde-3-phosphate dehydrogenase
      mRNA levels did not change with age indicating that the decrease in L7 mRNA was
      not a result of a general decrease in mRNA with age. These observations are
      consistent with the hypotheses that decreasing L7 mRNA levels are associated with
      aging and that late passage fibroblasts have features in common with senescence.
      The observations are not consistent with the hypothesis that senescent changes in
      cellular function are caused by terminal differentiation.

PMID- 8137893
TI  - Age-related changes in polyamine biosynthesis after fasting and refeeding.
AB  - The effect of aging on ornithine decarboxylase (ODC) activity and polyamine
      biosynthesis in the proximal small intestine was studied in two groups of male
      Fisher 344 rats (young [4-month old] and aged [26- to 27-month old]) using a
      fasting and refeeding model. In control (nonfasted) rats, levels of polyamines
      (putrescine, spermidine and spermine) and ODC activity were significantly higher
      in aged compared with young rats. In aged rats, fasting significantly reduced the
      levels of putrescine by 41%, spermidine by 23%, and spermine by 11%; however,
      fasting had no effect on polyamine levels in young rats. ODC activity was
      decreased 75% in young and 50% in aged rats after fasting compared with the
      respective age-matched controls. Conversely, 2 h after reinstituting a chow diet
      increased ODC activity by 17-fold in young rats but only 8-fold in aged rats.
      Putrescine levels were also increased in both age groups after refeeding;
      however, similar to ODC activity, these increases were much less in aged rats. In
      addition, spermidine and spermine levels remained significantly depressed in the
      aged groups even after 24 h of refeeding. These findings suggest that the normal
      rigid control of gut polyamine biosynthesis and proliferation noted in young rats
      is markedly altered with aging.

PMID- 8137894
TI  - Metabolic heat production and cold tolerance during cold stress of different
      intensity of adult and aged male C57BL/6J mice.
AB  - Adult and aged male C57BL/6J mice were subjected to a 3-h cold stress test at
      either 24 degrees C, 18 degrees C, 12 degrees C, or 6 degrees C. Body mass was
      measured before the test, and colonic temperature, O2 consumption, and CO2
      production were measured during the test. The slopes of colonic temperature over
      time of test and the mean metabolic heat production were calculated for each
      animal. While adult mice had a relatively small reduction in colonic temperature
      during the test at all four ambient temperatures, in the aged mice ambient
      temperatures resulted in steeper reductions of colonic temperature. In adult
      mice, an increase in metabolic heat production was proportional to ambient cold.
      The thermogenic response of aged mice at 24 degrees C and at 18 degrees C was
      similar to adult mice, suggesting that the ability of aged mice to respond to
      cold by increasing heat production does not diminish with age. However, in aged
      mice metabolic heat production at 12 degrees C and 6 degrees C was significantly
      below that of adult mice, which indicated a reduced capacity for thermogenesis.

PMID- 8137895
TI  - Slowing of age-specific mortality rates in Drosophila melanogaster.
AB  - We have studied age-dependent mortality in large cohorts of male and female D.
      melanogaster from four inbred lines. Average longevity varies substantially
      between genotypes (broad-sense heritability = 22%). Contrary to the predictions
      of the Gompertz model, mortality rates tend to decelerate at the most advanced
      ages. Fitting Gompertz, Weibull, Logistic, and Two-stage Gompertz mortality
      models to the data, we find that the best fit is obtained with the two-stage
      model, with exponentially increasing mortality at early ages, and zero or nearly
      zero increase at older ages. There is little microenvironmental effect from cage
      to cage. There is a sex-dependent mortality crossover: males and females differ
      in initial mortality rate and degree of acceleration of mortality rate, but the
      ordering of the sexes according to mortality parameters depends on genotype.
      Model fitting can be affected by gaps between deaths in the tail of the
      survivorship distribution. The observations are inconsistent with the limited
      life-span paradigm, which predicts sudden and well-defined drops in survivorship
      and corresponding sharp increases in mortality at advanced ages for large cohorts
      of genetically identical individuals.

PMID- 8137896
TI  - Effect of vitamin A on longevity.
AB  - Increasing the dietary content of Vitamin A from inadequate to adequate during
      the developmental stages of Drosophila increased the median life span by as much
      as 17.5%. The optimum dietary range of concentrations of Vitamin A for increasing
      the life span of Drosophila was found to be between 4 and 8 IU/g food. The
      maximum life span was reduced as dietary concentrations of Vitamin A exceeded
      this value. Vitamin A palmitate and retinal inhibited the peroxidation of
      linolenic acid induced by the generation of superoxide radicals from
      acetaldehyde. Other forms of Vitamin A, such as retinol and retinoic acid,
      moderately inhibited lipid peroxidation at low concentrations but stimulated
      peroxidation considerably when present at high concentrations. Based upon the
      ability of these retinoids to inhibit the reduction of cytochrome c by superoxide
      radicals, we propose that retinoids can inhibit and stimulate lipid peroxidation
      depending upon their concentration by reacting with superoxide radicals. We
      suggest that this reaction is the basis for the apparent ability of Vitamin A to
      prolong and shorten life span depending upon the dietary intake.

PMID- 8137897
TI  - Hypergravity and aging in Drosophila melanogaster: 7. New longevity data.
AB  - Longevity of mated and virgin Drosophila melanogaster flies was observed at
      various gravity levels (1-7.38 g). A slight longevity decrease was observed in
      the 1-5.14 g range for virgin males, and a larger one in the 5.14-7.38 g range.
      The effect of gravity was larger for females in the 1-5.14 g range, and at the
      highest gravity level, both sexes had roughly the same longevity, which however
      remained high (around 40 days). The longevity of mated flies was lower than that
      of virgins at 1 g, and only a slight longevity decrease was observed in the 1
      7.38 g range in females, this decrease being larger for males. Hypergravity
      appears to have no dramatic effects on life span and to be of lower importance
      than the simple effect of mating. This study confirms previous results obtained
      in the 1-5.02 g range with virgin flies (Le Bourg and Lints, 1989).

PMID- 8137898
TI  - Effects of mating status, sex ratio, and population density on longevity and
      offspring production of Cryptolestes ferrugineus (Stephens) (Coleoptera:
      Cucujidae).
AB  - The life span and reproductive rate of the rusty grain beetle, Cryptolestes
      ferrugineus (Stephens), were determined at different adult densities and sex
      ratios at 30 +/- 1 degree C, 75 +/- 5% relative humidity (RH), and with feed
      consisting of ground wheat plus wheat germ (4:1, w/w). The mean life spans of
      adult beetles were 32 weeks for adults individually isolated in separate vials,
      22 to 25 weeks for adults of different strains kept one male and one female per
      vial, 24 weeks for a group of 30 virgin females together in one vial, 13 weeks
      for a group of 30 virgin males together in one vial, 14 weeks for groups with 10
      males and 20 females per vial, 13 weeks for groups with 15 males and 15 females
      per vial, and 12 weeks for groups with 20 males and 10 females per vial. When
      kept one adult per vial, males and females had similar life spans; when kept one
      male and one female per vial, males lived longer; when kept in groups of 30 per
      vial females lived longer, except in the group which had a sex ratio of two males
      to one female; in this group life spans of males and females were the same.
      Females in separate vials with one male produced mean numbers of of offspring
      ranging from 389 for an inbred homozygous malathion-resistant strain to 514 for
      an outbred strain (genetically variable: GV). GV strain females in vials which
      had 10 males and 20 females produced a mean of 97 offspring, GV strain females in
      vials which had 15 males and 15 females produced a mean of 146 offspring, and GV
      strain females in vials which had 20 males and 10 females produced a mean of 216
      offspring. The results of this study and similar studies on other insect species
      suggest that the life span of this insect is inversely related to the rate at
      which it expends energy and to injury incurred during copulation, and that
      oviposition rate decreases as the density of larvae and female adults increases.

PMID- 8137899
TI  - Effects of lipid peroxide on production of matrix metalloproteinase 1 (tissue
      collagenase) and 3 (stromelysin) and tissue inhibitor metalloproteinase 1 by
      human rheumatoid synovial fibroblasts.
AB  - The effects of linoleic acid hydroperoxide on the production of matrix
      metalloproteinases (MMPs) including MMP-1 (tissue collagenase), -2 ("type IV
      collagenase"), and -3 (stromelysin) and of tissue inhibitor of metalloproteinase
      1 (TIMP-1), as well as DNA synthesis were investigated in rheumatoid synovial
      fibroblasts. Our results demonstrated that the levels of proMMP-1 and -3 and TIMP
      1 were extremely elevated when 0.5-2.0 nmole/ml of linoleic acid hydroperoxide
      was added to cultures of rheumatoid synovial fibroblasts. DNA synthesis, however,
      was inhibited by linoleic acid hydroperoxide. These results indicate that lipid
      peroxide causes the disruption of extracellular matrix macromolecules and the
      inhibition of cell repair in synovial tissue. Therefore, they also suggest that
      an elevated level of oxygen free radical and/or lipid peroxides in synovial fluid
      may play an important role in the process of rheumatoid arthritis, resulting in
      the disruption of the joint.

PMID- 8137900
TI  - Exponential relationship between plasma cholesterol levels and atherosclerotic
      lesion size in hyperlipidemic swine.
AB  - The effect of fish oil supplements on atherogenesis is controversial, especially
      when fish oil does not lower plasma cholesterol. Some studies in swine have shown
      that a fish oil supplement to a butter-cholesterol diet reduces atherogenesis.
      The fish oil supplement also frequently reduces average plasma cholesterol
      levels. The reduction in lesion size has been shown to be greater than can be
      expected from average plasma cholesterol reductions, if a linear relationship
      between lesion size and plasma cholesterol was assumed. However, in an experiment
      in which we equalized time-weighted average plasma cholesterol levels, there was
      no significant reduction in lesion size in the fish oil supplemented group. This
      led us to question the validity of the linear relationship between lesion size
      and plasma cholesterol level. In this study we have combined the results of eight
      study blocks with a total of 76 swine fed a similar hyperlipidemic, butter
      cholesterol diet. Of these, 24 received a fish oil supplement (BT+fish oil) and
      52 swine received no fish oil supplement (BT). The average lesion size as
      measured by nuclear profiles per cross section of a fixed site in the abdominal
      aorta (ABNpCx) was 7704 +/- 778 (mean +/- SEM) for the BT group and 2360 +/- 1145
      for the BT+fish oil group. Total plasma cholesterol levels were measured at the
      outset and at monthly intervals until sacrifice. For each animal we obtained a
      time-weighted average based on the trapezoidal rule.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8137901
TI  - Ultrastructural localization of DNA in leukemic cells using osmium ammine B.
AB  - In order to determine whether there were any differences in distribution of
      nuclear DNA between acute lymphocytic leukemia (ALL) and acute myelogenous
      leukemia (AML), the localization of DNA in blasts from the bone marrow or buffy
      coat of 30 patients with ALL and 30 patients with AML was examined
      ultrastructurally by staining with osmium ammine B. By the ultrastructural
      cytochemistry, DNA in ALL cells was clumped in the nuclei, while in AML cells, it
      was dispersed. DNA had accumulated around the nucleoli of some blasts, and flecks
      of DNA were observed in nucleoli of a majority of blasts. The perinucleolar and
      intranucleolar DNA distribution could be classified into four types. The types
      with abundant perinucleolar DNA were frequently observed in ALL blasts, while the
      majority of AML blasts showed scant perinucleolar DNA. The types with
      intranucleolar flecks of DNA were more prominent in leukemic cells than in normal
      immature leukocytes. In conclusion, the pattern of distribution of DNA in the
      nuclei of leukemic cells differs between ALL and AML.

PMID- 8137902
TI  - Molecular structural changes in Mallory body proteins in human and mouse livers:
      an infrared spectroscopy study.
AB  - To study the molecular structure of Mallory body (MB) proteins we applied
      infrared spectroscopy of the isolated MBs from livers obtained from autopsied
      patients with alcoholic cirrhosis and griseofulvin-fed (GF-fed) mice. Liver
      frozen sections were extracted with detergent and digested with deoxyribo- and
      ribonuclease and collagenase. MB-enriched fractions were then separated out using
      the aqueous two-phase polymer system. Immunohistochemical and electron
      microscopic examination showed that the MB composition was virtually identical in
      human and mouse livers. Infrared spectra of both MB samples showed that the MBs
      had more numerous and stronger intermolecular hydrogen bonding than did the
      background control fractions as well as the cytoskeletal fraction from control
      and GF-fed mice. This may explain why the proteins in MBs are aggregated. The
      relative amount of beta-sheets was increased compared to the alpha-helices in the
      MBs, indicating that conformational changes in the cytokeratin peptides of the
      MBs had occurred. This may explain why the antigenic sites observed in MB
      proteins show changes in affinity for antibodies to cytokeratins as observed by
      immunohistochemical staining of MBs.

PMID- 8137903
TI  - The effect of transforming growth factor beta 1 on mesangial cell fibronectin
      synthesis: increased incorporation into the extracellular matrix and reduced pI
      but no effect on alternative splicing.
AB  - Fibronectin is a multidomain glycoprotein which accumulates in mesangial
      proliferative glomerulonephritis (MPGN). Recent evidence has implicated
      transforming growth factor beta (TGF-beta) in the pathogenesis of experimental
      MPGN. We have, therefore, examined the influence of TGF-beta 1 on mesangial cell
      fibronectin synthesis. Considering, first, levels of mRNA, TGF-beta 1 increased
      steady-state fibronectin RNA in cultured mesangial cells by 1.9 times 24 hr after
      treatment of cycling mesangial cells and by 11.8 times in growth-arrested cells.
      There was, however, no alteration in fibronectin pre-mRNA splicing in either the
      EIIIA or IIICS regions. Fibronectin protein concentrations in cell culture
      supernatants, determined by immunoprecipitation of supernatants from cells
      labeled with [35S]methionine and by ELISA, were not increased by treatment with
      TGF-beta 1. Western blots and immunoprecipitation of metabolically labeled cells
      showed that fibronectin was increased, however, in the deoxycholate-insoluble
      extracellular matrix (ECM) of cells stimulated with TGF-beta 1. TGF-beta 1
      altered the physicochemical properties of fibronectin in ECM and supernatant such
      that the isoelectric point of fibronectin, determined from Western blots of 2D
      SDS-PAGE gels, was reduced so that both became more acidic. These studies
      demonstrate, therefore, that in addition to increasing its synthesis, TGF-beta 1
      increases incorporation of fibronectin into the ECM. Because fibronectin
      possesses binding sites for other ECM proteins, greater incorporation of
      fibronectin following TGF-beta 1 treatment may be an important pathogenetic
      mechanism in mesangial sclerosis. Moreover, the altered charge of fibronectin may
      increase localization of serum immunoglobulins to the mesangium.

PMID- 8137904
TI  - Response of femoral arteries of cholesterol-fed rabbits to balloon angioplasty
      with or without laser: emphasis on the distribution of foam cells.
AB  - Very little is known about the structural composition of the restenotic plaque in
      evolution. The responses of atherosclerotic femoral arteries of rabbits to
      balloon angioplasty (BA), thallium/holmium/chromium: YAG infrared laser
      angioplasty (LA), combined LA and BA, or no angioplasty were compared by blinded
      quantitative histomorphometry and angiography. The endothelium was injured by
      nitrogen/air desiccation, and the animals were fed a 2% cholesterol diet for 1
      month prior to the angioplasty procedure. Animals were sacrificed 2 hr or 28 days
      after angioplasty by pressure perfusion with 10% formaldehyde (100 mm Hg), and
      arterial segments (4-5 cm) were excised bilaterally. The frequency of thrombus
      was greatest in arteries with LA. Arteries with combined LA and BA had the
      greatest initial gain in luminal diameter by angiography, but they also had the
      greatest reduction in luminal diameter from 2 hr to 28 days and the greatest
      cross-sectional area narrowing by plaque at 28 days. The principal component of
      the intimal plaques in all groups was fibrous tissue (approximately 90%), with
      the remainder consisting primarily of "foam cells." By multiple regression
      analysis, the strongest predictors of cross-sectional area narrowing were
      contiguity of foam cells between the intima and media, depth of the tear,
      percentage of foam cells in the plaque, and the intervention of LA followed by
      BA. The principal predictors of foam cells in the plaque, irrespective of
      treatment, were also cross-sectional area narrowing, contiguity of foam cells
      between plaque and media, and the depth of tear. It is suggested that a large
      proportion of the foam cells of the intima may be derived from foam cells of the
      media and adventitia rather than from the lumen. These observations may be of
      particular importance regarding angioplasty in young people where foam cells
      occupy a significantly greater proportion of the atherosclerotic plaque.

PMID- 8137905
TI  - Cytochrome oxidase evolved by tinkering with denitrification enzymes.
AB  - The cytochrome bc complex which is encoded by the fixNOPQ operon in
      Bradyrhizobium japonicum, is the most distant member of the haem-copper
      cytochrome oxidase family. We have found that its major subunit, FixN, is
      homologous to the NorB subunit of nitric oxide reductase in a purple bacterium. A
      second evolutionary link between cytochrome oxidases and denitrification enzymes
      is the presence of a similar binuclear copper site in cytochrome aa3 (the
      mitochondrial oxidase) and nitrous oxide reductase. This centre was probably
      acquired by a primitive FixN-type oxidase, leading to the evolution of the
      mitochondrial-type oxidase. These links suggest that the oxygen-reducing
      respiratory chain developed from the anaerobic, denitrifying respiratory system.

PMID- 8137906
TI  - Flash-induced electrogenic reactions in the SA(L223) reaction center mutant in
      Rhodobacter sphaeroides chromatophores.
AB  - The charge transfer events in the SA(L223) reaction center mutant Rhodobacter
      sphaeroides chromatophores were investigated by direct electrometry. Besides the
      primary charge separation, the small stigmatellin-sensitive electrogenic reaction
      due to the electron transfer from the primary to the secondary quinone acceptor
      in the reaction center complex was observed after the first flash. The second
      flash-induced electrogenic phase of the secondary quinone protonation and
      subsequent electrogenic reactions of the cytochrome bc1 complex were much slower
      than those in chromatophores of the wild type. It is suggested that replacement
      of Ser-L223 by Ala impairs both specific proton-conducting pathways leading to
      the secondary quinone QB.

PMID- 8137907
TI  - Mutagenesis of Phe381 and Phe382 in the extracellular domain of the insulin
      receptor: effects on receptor biosynthesis, processing, and ligand-dependent
      internalization.
AB  - Mutations of the extracellular domain of the insulin receptor impair processing
      and transport of receptors to the plasma membrane. We have previously reported
      that a mutation substituting Val for Phe382 in the alpha-subunit of the insulin
      receptor impairs intracellular processing and insulin-induced autophosphorylation
      of the mutant receptor. In this investigation, we have generated two independent
      mutations of amino acids Phe381 and Phe382 of the insulin receptor: Val for
      Phe381 and Leu for Phe382. These substitutions cause a slight impairment of
      intracellular processing and transport of the mutant receptors. Furthermore,
      insulin-dependent internalization of the mutant receptors is unaffected by these
      mutations. Thus, of the three substitutions studied to date, Val for Phe382 is
      the only mutation of the Phe381-Phe382 sequence that causes a major defect in
      post-translational processing of the receptor.

PMID- 8137908
TI  - Progesterone increases the production of tissue inhibitor of metalloproteinases-2
      in rabbit uterine cervical fibroblasts.
AB  - Rabbit uterine cervical fibroblasts in culture produces tissue inhibitor of
      metalloproteinases (TIMP)-1 and TIMP-2. When cells were treated with
      physiological concentrations of progesterone, the production of two TIMPs
      increased, and essentially all TIMP-2 was found to be complexed with promatrix
      metalloproteinase 2 (proMMP-2)/progelatinase A. Progesterone did not modulate the
      production of proMMP-2 and resulted in the increased total amount of proMMP-2
      TIMP-2 complex. These observations provide the first evidence that progesterone
      participates in maintaining the homeostasis of connective tissue matrix in
      uterine cervix by augmenting both TIMP-1 and TIMP-2 production along with the
      known suppressive effects on the proMMP-1 and proMMP-3 production.

PMID- 8137909
TI  - Phosphoinositide 3-phosphatase segregates from phosphatidylinositol 3-kinase in
      EGF-stimulated A431 cells and fails to in vitro hydrolyse
      phosphatidylinositol(3,4,5)trisphosphate.
AB  - Beside 4- and 5-phosphatases playing a role in the interconversion between the D
      3 phosphorylated polyphosphoinositides, the only enzyme described so far to be
      responsible for a phosphomonesterasic activity on the D-3 position of inositol
      lipids is a specific 3-phosphatase that hydrolyzes PtdIns(3)P in NIH 3T3 cells.
      We report here the presence of a potent 3-phosphatase activity in different cell
      types. This activity is detected both in cytosol and membranes of A431 cells and
      is inhibited by VO4(-3) and Zn2+. Interestingly, the cytosolic activity from A431
      cells selectively hydrolyzes in vitro PtdIns(3)P and PtdIns(3,4)P2, whereas
      PtdIns(3,4,5)P3 remains a very poor substrate under the same conditions. Finally,
      assays of phosphatidylinositol 3-kinase and 3-phosphatase activities in the pool
      of phosphotyrosine-containing proteins isolated from EGF-stimulated A431 cells
      suggest a compartmentation of these two antagonistic activities during cell
      activation.

PMID- 8137910
TI  - The threonine residues in MAP kinase kinase 1 phosphorylated by MAP kinase in
      vitro are also phosphorylated in nerve growth factor-stimulated rat
      phaeochromocytoma (PC12) cells.
AB  - The residues on MAP kinase kinase-1 (MAPKK1) phosphorylated by MAP kinase in
      vitro have been identified as Thr-291 and Thr-385. Both threonines are
      phosphorylated in PC12 cells and the 32P-labelling of each residue increases
      after stimulation with nerve growth factor (NGF). The results establish that
      MAPKK1 is a physiological substrate for MAP kinase. The two active forms of MAPKK
      that are resolved by Mono Q chromatography of PC12 cell extracts are both
      phosphorylated at Thr-291 and Thr-385, demonstrating that neither species is the
      MAPKK2 isoform which lacks Thr-291.

PMID- 8137911
TI  - Mechanisms of stimulus-evoked intracellular acidification in frog nerve fibres.
AB  - Measurements of cytoplasmic pH (pHi) in frog nerve fibers (sciatic nerve and its
      thin bundles) were performed by using fluorescein diacetate. Earlier it had been
      established that veratridine (VER) treatment of the nerve greatly enhances the
      stimulus-evoked intracellular acidification (SEIA) which becomes irreversible
      after blockade of the Na+/K+ pump with ouabain. Present experiments have shown
      that inhibition of lactic acid production by iodacetamide (5 mM) or blockade of
      Cl- influx by SITS do not prevent or attenuate the VER- and stimulus-evoked
      decrease in pHi. Blockade of Na+/H+ exchange by EIPA impedes pHi recovery
      following repetitive stimulation. Lowering of external pH (pHe) to 6.5 enhances,
      while elevation of pHe to 9.5 greatly diminishes SEIA, both in the presence or
      absence of VER. The hypothesis is put forward that SEIA results from excessive
      influx of H+ and Na+ into the fiber via activated Na+ channels: internal Na+
      suppresses Na+/H+ exchange which potentiates the pHi decrease caused by H+
      influx.

PMID- 8137912
TI  - Inhibitor analysis of calf thymus DNA polymerases alpha, delta and epsilon.
AB  - Quantitative effects of inhibitors of the replicative DNA polymerases (pol)
      alpha, delta and epsilon from calf thymus are reported under similar assay
      conditions. Carbonyldiphosphonate was a competitive inhibitor of pols delta and
      epsilon, with 4- to 6-fold selectivity compared to pol alpha. Aphidicolin
      inhibited pols alpha and delta with 6- to 10-fold selectivity compared to pol
      epsilon. The 'butylphenyl' nucleotides, BuPdGTP and BuAdATP, inhibited pol alpha
      with at least 1000-fold selectivity compared to pols delta and epsilon. The use
      of these inhibitors under similar assay conditions permits the discrimination of
      the three enzymes.

PMID- 8137913
TI  - Expression and stability of recombinant RQ-mRNAs in cell-free translation
      systems.
AB  - Expression of dihydrofolate reductase (DHFR) and chloramphenicol
      acetyltransferase (CAT) mRNAs in cell-free Escherichia coli translation systems
      is greatly enhanced as a result of their insertion into RQ135 RNA, a naturally
      occurring satellite of phage Q beta. The enhancement is due to protection of the
      recombinant mRNAs against endogenous ribonucleases and to an increased initial
      rate of translation in the case of the RQ-CAT mRNA.

PMID- 8137915
TI  - The molten globule is a third thermodynamical state of protein molecules.
AB  - Analysis of published data on conformational transitions in relatively small
      proteins shows that the slopes of these transitions are proportional to the
      protein molecular weight. It is true both for transitions from the native (N) to
      the unfolded (U) states (when protein denaturation is coupled to its unfolding)
      and for transitions from the native to the molten globule (MG) states and from
      the molten globule to the unfolded state (when protein denaturation is decoupled
      from protein unfolding). This is precisely the behaviour predicted by
      thermodynamics for first order phase transitions ('all-or-none' transitions) in
      small systems. It follows that N-->U, N-->MG and MG-->U transitions in proteins
      are all of the 'all-or-none' type. Thus the molten globule state of protein
      molecules is separated by an 'all-or-none' transition both from the native and
      the unfolded state, i.e. the molten globule state is a third thermodynamic state
      of protein molecules in addition to the two previously established states--the
      native and the unfolded.

PMID- 8137914
TI  - An unusual metal-binding cluster found exclusively in the avian breast muscle
      troponin T of Galliformes and Craciformes.
AB  - A repeating metal-binding (Cu2+ > Ni2+ > Zn2+ approximately Co2+) sequence
      (HE/AEAH)4 has been identified in troponin T isoforms specifically expressed in
      the breast but not leg muscles of all Galliformes and Craciformes. It is absent
      in the skeletal and cardiac muscles of mammals and all other avian species
      investigated. Concentration of the metal-binding sites is adequate to affect free
      metal levels in the muscle cell and we suggest a possible link between its
      presence in breast muscle of Galliformes and the high ratio of breast muscle to
      total body muscle mass and explosive but short-lived flight pattern of these
      birds. This sequence can be used for a highly selective metal-affinity
      chromatographic purification of muscle or engineered TnTs even in high salt
      and/or urea.

PMID- 8137916
TI  - Prothymosin alpha receptors on peripheral blood mononuclear cells.
AB  - 125I-Labeled prothymosin alpha (ProT alpha) was used to study the presence and
      characteristics of receptors for ProT alpha on human peripheral blood mononuclear
      cells (PBMC). The kinetics of 125I-ProT alpha binding to PBMC was fast at 37
      degrees C, whilst it required 50 min to reach equilibrium at 4 degrees C and room
      temperature. Analysis of steady state binding data by the method of Scatchard and
      by unlabeled ProT alpha competition experiments identified two binding sites with
      an apparent equilibrium dissociation constant of 216-321 pM for the high-affinity
      receptor and of 11.4-21.1 nM for the low-affinity one; the sites per cell ranged
      from 1,479 to 1,519 and from 47,547 to 56,169, respectively. The kinetically
      derived equilibrium dissociation constant agreed with these data and showed no
      interaction between receptors.

PMID- 8137917
TI  - pH-dependent interaction of an intraluminal loop of inositol 1,4,5-trisphosphate
      receptor with chromogranin A.
AB  - The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store role of the secretory
      vesicles of adrenal medullary chromaffin cells is attributed to the presence of
      high capacity, low affinity Ca2+ binding protein chromogranin A. Chromogranin A
      has recently been shown to interact with the protein component(s) on the
      intraluminal side of the secretory vesicle membrane at the intravesicular pH of
      5.5 but to dissociate from them at the near physiological pH of 7.5. Further, one
      of the chromogranin A-interacting membrane proteins was tentatively identified as
      the IP3 receptor. Therefore, the pH-dependent potential interaction of the
      intraluminal loop domains of the IP3 receptor with chromogranin A was studied by
      analytical ultracentrifugation utilizing synthetic intraluminal loop peptides of
      the IP3 receptor labeled with 5-hydroxy-tryptophan at the N-terminus as a
      chromophore. One of the intraluminal loop domains was found to interact with
      chromogranin A at pH 5.5 but not at pH 7.5, suggesting the importance of the
      intraluminal loop domain in transmitting Ca2+ mobilization signals to
      chromogranin A.

PMID- 8137918
TI  - ORL1, a novel member of the opioid receptor family. Cloning, functional
      expression and localization.
AB  - Selective PCR amplification of human and mouse genomic DNAs with oligonucleotides
      encoding highly conserved regions of the delta-opioid and somatostatin receptors
      generated a human DNA probe (hOP01, 761 bp) and its murine counterpart (mOP86,
      447 bp). hOP01 was used to screen a cDNA library from human brainstem. A clone
      (named hORL1) was isolated, sequenced and found to encode a protein of 370 amino
      acids whose primary structure displays the seven putative membrane-spanning
      domains of a G protein-coupled membrane receptor. The hORL1 receptor is most
      closely related to opioid receptors not only on structural (sequence) but also on
      functional grounds: hORL1 is 49-50% identical to the murine mu-, delta- and kappa
      opioid receptors and, in CHO-K1 cells stably transfected with a pRc/CMV:hORL1
      construct, ORL1 mediates inhibition of adenylyl cyclase by etorphine, a
      'universal' (nonselective) opiate agonist. Yet, hORL1 appears not to be a typical
      opioid receptor. Neither is it a somatostatin or sigma (N-allylnormetazocine)
      receptor. mRNAs hybridizing with synthetic oligonucleotides complementary to
      mOP86 are present in many regions of the mouse brain and spinal cord,
      particularly in limbic (amygdala, hippocampus, septum, habenula, ...) and
      hypothalamic structures. We conclude that the hORL1 receptor is a new member of
      the opioid receptor family with a potential role in modulating a number of brain
      functions, including instinctive behaviours and emotions.

PMID- 8137919
TI  - Phosphate-activated glutaminase expression during tumor development.
AB  - Changes in phosphate-activated glutaminase activities determined in intact cells
      and isolated mitochondria have been followed during mouse Ehrlich ascites
      carcinoma development. Glutaminase activities parallel the levels of poly(A)+
      RNAs encoding for the mitochondrial phosphate activated glutaminase. During the
      exponential growth phase, maximum activity was observed and the relative
      abundance of glutaminase mRNA significantly increased with regard to the
      stationary growth phase. The presented results show that tumor phosphate
      activated glutaminase is subject to long-term regulation by differential gene
      expression.

PMID- 8137920
TI  - Expression and characterization of VIP and two VIP mutants in NIH 3T3 cells.
AB  - Prepro-vasoactive intestinal peptide (prepro VIP) was expressed in NIH 3T3 cells,
      and the prepro VIP-derived peptides produced by the cells were analyzed by
      chromatography combined with sequence-specific radio-immunoanalysis. In
      accordance with what has previously been reported on processing in non-endocrine
      cell lines, the VIP precursor was processed poorly in these non-endocrine cells.
      Mainly an extended form of VIP could be detected in the media from the cells, and
      no immunoreactivity specific for amidated VIP was found. However, by changing the
      dibasic cleavage site positioned N-terminal to the VIP sequence in the precursor
      into the consensus sequence (Arg, X,Lys/Arg,Arg) for the ubiquitous processing
      enzyme furin, thought to process, e.g. insulin receptors, factor VII, and by
      deleting residues 156-170 in the VIP precursor, expression of amidated VIP was
      obtained in this fibroblast cell line. Peptides from the wild-type VIP precursor
      as well as peptides from the mutated VIP precursor were found to be able to
      stimulate the adenylate cyclase in cells expressing the VIP receptor.

PMID- 8137921
TI  - Photophobic responses and phototaxis in Chlamydomonas are triggered by a single
      rhodopsin photoreceptor.
AB  - The rhodopsin nature of the photoreceptor for the behavioural light responses in
      Chlamydomonas has originally been revealed by action spectroscopy. Meanwhile most
      physiological experiments and the identification of all-trans-retinal in cell
      extracts favour that this chlamyrhodopsin contains an all-trans-type retinal
      chromophore with strong similarity to the light sensors SR I and SRII from
      Halobacteria. Reconstitution of retinal-deficient cells with [3H]retinal
      identified a single retinal protein with a MW of 30,000. Chlamyrhodopsin triggers
      a photoreceptor current in the eyespot region resulting in direction changes or
      phototaxis. Furthermore, when the light stimulus oversteps a critical level, two
      flagellar currents appear, which are the basis for photophobic responses. The
      physiological, electrophysiological and biochemical experiments suggest that all
      behavioural responses are triggered by a single rhodopsin-type receptor.

PMID- 8137922
TI  - The thrombospondin-like chains of cartilage oligomeric matrix protein are
      assembled by a five-stranded alpha-helical bundle between residues 20 and 83.
AB  - The N-terminal fragment of rat cartilage oligomeric matrix protein (COMP),
      comprising residues 20-83, was over-expressed in E. coli and purified under non
      denaturing conditions. The fragment forms pentamers similar to the assembly
      domain of the native protein. Its five chains can be covalently linked in vitro
      by oxidation of cysteines 68 and 71. The fragment adopts a predominantly alpha
      helical structure as judged by circular dichroism spectroscopy. On the basis of
      these findings we propose the model of a five-stranded alpha-helical bundle for
      the assembly domain of COMP. The studied sequence is conserved in thrombospondins
      3 and 4 thus raising the possibility that these proteins are also pentamers.

PMID- 8137923
TI  - Oxidative DNA base damage and antioxidant enzyme activities in human lung cancer.
AB  - We have investigated levels of antioxidant enzymes and free radical-induced DNA
      base modifications in human cancerous lung tissues and in their cancer-free
      surrounding tissues. Various DNA base lesions in chromatin of lung tissues were
      measured by gas chromatography-mass spectrometry. Activities of superoxide
      dismutase, catalase and glutathione peroxidase were also measured in lung
      tissues. Higher levels of DNA lesions were observed in cancerous tissues than in
      cancer-free surrounding tissues. Antioxidant enzyme levels were lower in
      cancerous tissues. The results indicate an association between decreased
      activities of antioxidant enzymes and increased levels of DNA lesions in
      cancerous tissues. Higher levels of DNA lesions suggest that free radical
      reactions may be increased in malignant tumor cells.

PMID- 8137924
TI  - Kinetics of nitric oxide and hydrogen peroxide production and formation of
      peroxynitrite during the respiratory burst of human neutrophils.
AB  - Nitric oxide (.NO) release, oxygen uptake and hydrogen peroxide (H2O2) production
      elicited by increasing phorbol 12-myristate 13-acetate (PMA) concentrations were
      measured in human neutrophils. Half-maximal activities were sequentially elicited
      at about 0.0001-0.001 micrograms PMA/ml (.NO) and 0.001-0.01 micrograms PMA/ml
      (H2O2). At saturated PMA concentrations, .NO production, oxygen uptake and H2O2
      release were 0.56 +/- 0.04, 3.32 +/- 0.52 and 1.19 +/- 0.17 nmol.min-1.10(6)
      cells-1. .NO production accounts for about 30% of the total oxygen uptake.
      Luminol-dependent chemiluminescence, reported to detect NO reactions in other
      inflammatory cells, was also half-maximally activated at about 0.001-0.01
      micrograms PMA/ml. Preincubation with NG-monomethyl-L-arginine (L-NMMA) decreased
      O2 uptake and .NO release but increased H2O2 production, while superoxide
      dismutase (SOD) increased .NO detection by 30%. Chemiluminescence was also
      reduced by preincubation with L-NMMA and/or SOD. The results indicate that .NO
      release is part of the integrated response of stimulated human neutrophils and
      that, in these cells, kinetics of .NO and O2.- release favour the formation of
      other oxidants like peroxynitrite.

PMID- 8137925
TI  - Low density lipoprotein oxidizability by copper correlates to its initial
      ubiquinol-10 and polyunsaturated fatty acid content.
AB  - At an early stage of oxidation induced by Cu2+, the rate of oxidative
      modification of human low density lipoprotein (LDL) from healthy donors
      correlated negatively to its ubiquinol-10 (r = -0.58, P < 0.01) and positively to
      its polyunsaturated fatty acid (PUFA) (r = 0.53, P < 0.05) content. The
      PUFA/ubiquinol-10 ratio was the best predictor of LDL susceptibility to oxidation
      (r = 0.68, P < 0.01). No significant correlation between LDL oxidizability and
      its alpha-tocopherol content was found at any oxidation stage. It is suggested
      that ubiquinol-10 plays a central role in the early protection of LDL PUFAs
      against Cu(2+)-induced oxidation whereas alpha-tocopherol posesses both pro- and
      antioxidant activity.

PMID- 8137926
TI  - The binding of natural variants of human factor IX to endothelial cells.
AB  - The Gla-domain of human factor IX contains a specific element required for the
      binding of factor IX to an endothelial cell surface protein. We have investigated
      the dependence of this interaction on the structural integrity of the adjacent
      hydrophobic stack and epidermal growth factor-like domains. The ability of
      purified natural variants of human factor IX to compete with wild-type factor IX
      binding to the endothelial cell surface was used to obtain apparent Ki values of
      the variants. Our data suggest that the functional integrity of the Gla domain,
      enabling factor IX to specifically interact with an endothelial cell surface
      protein, depends on the structural and functional integrity of both the
      hydrophobic stack domain and the first epidermal growth factor-like domain.

PMID- 8137927
TI  - Amiodarone-induced hypercholesterolemia is associated with a decrease in liver
      LDL receptor mRNA.
AB  - Amiodarone decreases plasma and tissue triiodothyronine (T3) and increases plasma
      cholesterol levels resembling changes seen during hypothyroidism. To elucidate
      the mechanism of amiodarone-induced hypercholesterolemia we investigated gene
      expression of three key proteins in cholesterol metabolism (cholesterol 7 alpha
      hydroxylase, LDL receptor, HMG-CoA reductase) in livers of rats. Animals were
      treated with amiodarone or propylthiouracil (to induce mild hypothyroidism). The
      LDL receptor mRNA was downregulated (approximately 50%) in both amiodarone
      treated and hypothyroid animals, while the other mRNA remained unchanged after 14
      day treatment. The results suggest that amiodarone-induced hypercholesterolemia
      is associated with decreased LDL receptor mRNA levels.

PMID- 8137928
TI  - Effects of L-carnitine on the pyruvate dehydrogenase complex and carnitine
      palmitoyl transferase activities in muscle of endurance athletes.
AB  - The effects of L-carnitine on the pyruvate dehydrogenase (PDH) complex and
      carnitine palmitoyl transferase (CPT) were studied in muscle of 16 long-distance
      runners (LDR). These subjects received placebo or L-carnitine (2 g orally) during
      a 4-week period of training. Athletes receiving L-carnitine showed a dramatic
      increase (P < 0.001) in the PDH complex activities. By contrast, the levels of
      CPT, both 1 and 2, were unchanged. No significant changes were observed after
      placebo administration. We previously reported [Huertas R. et al., Biochem.
      Biophys. Res. Commun. 188 (1992) 102-107] that L-carnitine induces an increase in
      the activities of complexes I, III and IV of the respiratory chain in muscle of
      LDR. Taken together, our data suggest that the improvement in (maximal oxygen
      consumption) VO2max observed in LDR after L-carnitine administration is based on
      these biochemical findings.

PMID- 8137930
TI  - Inhibition of Moloney murine leukemia virus replication by tyrphostins, tyrosine
      kinase inhibitors.
AB  - We have previously shown that topoisomerase I (topo I) antagonist inhibited
      retrovirus replication. Since tyrphostins, synthetic compounds and protein
      tyrosine kinases (PTKs) blockers, inhibited topo I activity (manuscript in
      preparation) we examined their ability to inhibit Moloney murine leukemia virus
      (Mo-MuLV) replication. We found that non-cytotoxic doses of tyrphostin
      derivatives (AG-555, AG-18) blocked or substantially reduced Mo-MuLV replication
      in acute or chronically infected NIH/3T3 cells. Our experiments suggest that the
      antiviral effect of these tyrphostin derivatives was not the result of
      antiproliferative activity. However, the tyrphostin derivatives used in our
      present investigation differ in their ability to inhibit Mo-MuLV replication.
      Furthermore, as expected from stereospecific competitive inhibitors, the
      antiviral effect is not a general characteristic of all tyrphostin derivatives,
      since AG-213 does not affect Mo-MuLV replication. Our results indicate that these
      tyrphostin derivatives may represent a novel class of antiretroviral drugs.

PMID- 8137929
TI  - Dephosphorylation of microtubule-associated protein tau by protein phosphatase-1
      and -2C and its implication in Alzheimer disease.
AB  - Microtubule-associated protein tau is abnormally hyperphosphorylated and forms
      the major protein subunit of paired helical filaments (PHF) in Alzheimer disease
      brains. The abnormally phosphorylated sites Ser-199, Ser-202, Ser-396 and Ser-404
      but not Ser-46 and Ser-235 of Alzheimer tau were found to be dephosphorylated by
      protein phosphatase-1 and this dephosphorylation was activated by Mn2+. In
      contrast, protein phosphatase-2C did not dephosphorylate any of these sites. Both
      protein phosphatase-1 and -2C had high activities towards [32P]tau phosphorylated
      by cAMP-dependent protein kinase. These results suggest that both protein
      phosphatase-1 and -2C might be associated with normal phosphorylation state of
      tau, but only the former and not the latter phosphatase is involved in its
      abnormal phosphorylation in Alzheimer disease.

PMID- 8137931
TI  - How does NO activate hemeproteins?
AB  - NO was reported to activate guanylate cyclase and, recently, prostaglandin H
      synthase. NO interaction with the heme component in different hemeproteins is
      determined by ligand property, electronic configuration of the heme iron and the
      specific effects contributed by the protein structure. It is found that although
      NO interaction with the free heme provides some common rules of interaction, the
      consequences of NO binding to different hemeproteins should be dealt with
      individually.

PMID- 8137932
TI  - Molecular analysis of the IL-6 receptor in human multiple myeloma, an IL-6
      related disease.
AB  - A PCR-SSCP approach was used to search for mutations in IL-6 receptor genes in 9
      human plasma cell lines (HMCL) and in tumor plasma cells from 19 patients with
      fulminating multiple myeloma, an IL-6-related disease. Whereas no mutation was
      found in the cytokine receptor homologous (CRH) domain of IL-6R alpha, DNA and
      RNA polymorphisms in the gp130 CRH domain was detected in tumoral samples as well
      as in blood samples from healthy donors. Finally, mutations in the gp130 critical
      cytoplasmic domain were found in one HMCL and in tumor plasma cells of one
      patient. Only the mutated allele was expressed in the HMCL.

PMID- 8137933
TI  - The first cytoplasmic loop of the thyrotropin receptor is important for
      phosphoinositide signaling but not for agonist-induced adenylate cyclase
      activation.
AB  - We investigated the role of the 1st cytoplasmic loop of the thyrotropin receptor
      (TSHR) on signal transduction using mutants as we did the 2nd and 3rd cytoplasmic
      loops [Kosugi S. et al. (1994) Mol. Endocrinol., in press; and 7, 1009-1020].
      Five substitution mutants involving the first cytoplasmic loop showed a TSH- or
      Graves' IgG-stimulated cAMP response despite the low TSH binding Bmax. All the
      mutants completely lost or markedly decreased the TSH- or Graves' IgG-stimulated
      inositol phosphate increase. These findings suggest that the 1st cytoplasmic loop
      of the TSHR does not play a crucial role in agonist-induced adenylate cyclase
      activation but that it is important for phosphoinositide signaling.

PMID- 8137934
TI  - The three-dimensional structure of the complex of proteinase K with its naturally
      occurring protein inhibitor, PKI3.
AB  - Proteinase K forms a 1:1 stable complex with its naturally occurring protein
      inhibitor, PKI3. The crystal structure of this complex has been determined by a
      combination of molecular replacement and single isomorphous replacement methods.
      The model comprises all of the 459 residues: 279 for proteinase K and 180 for
      PKI3, and it was refined to an R-factor of 19.2% at a resolution of 2.5 A.
      Association of these two molecules in the complex indicates the binding of PKI3
      in the substrate recognition site of the enzyme. The active serine residue of
      proteinase K in this complex possesses a somewhat different configuration to that
      found in its native structure and hence renders the enzyme inactive.

PMID- 8137935
TI  - Drosophila lebanonensis ADH: analysis of recombinant wild-type enzyme and site
      directed mutants. The effect of restoring the consensus sequence in two
      positions.
AB  - Unique amino acid substitutions occur in D. lebanonensis ADH. They are found
      within the putative NAD(+)-binding domain and affect residues that are otherwise
      highly conserved in all other species of the genus. To restore the consensus
      amino acids, we have constructed an expression system for this enzyme in E. coli,
      and engineered two mutants, Ala13Gly and Asn56Thr. The biochemical and kinetic
      features of these retromutants are consistent with increased catalytic efficiency
      and thermal stability. Thus, results show that wild-type D. lebanonensis ADH can
      be improved by site-directed mutagenesis.

PMID- 8137936
TI  - Induction of aromatase in stromal vascular cells from human breast adipose tissue
      depends on cortisol and growth factors.
AB  - The regulation of aromatase (estrogen synthase) activity of cultured stromal
      vascular cells from human breast adipose tissue by cortisol, db-cAMP and growth
      factors was studied in a serum-free culture system. While PDGF-BB alone inhibited
      the effect of db-cAMP on aromatase induction, it stimulated aromatase activity in
      the presence of cortisol with or without db-cAMP. In the presence of 1 microM
      insulin consistently higher aromatase activities were found as compared to 1 nM
      insulin. In contrast to PDGF-BB, bFGF led to an increase of aromatase activity
      only in the presence of both cortisol and db-cAMP.

PMID- 8137937
TI  - cDNA cloning, expression and primary structure of Par jI, a major allergen of
      Parietaria judaica pollen.
AB  - A 659 bp cDNA clone** coding for an allergen of Pj pollen has been isolated from
      a lambda gt11 library, and its DNA sequence determined. The cDNA insert showed an
      open reading frame of 429 bp coding for an allergenic protein of 14,866 Da and a
      deduced amino acid sequence containing 143 residues. The expressed recombinant
      protein represented the major allergen Par jI since it reacted with 95% of the
      sera from Pj-allergic patients (n = 22) and with two Par jI-specific monoclonal
      antibodies. No similarity with other known DNA and protein sequences has been
      detected.

PMID- 8137938
TI  - Both interleukin-8 receptors independently mediate chemotaxis. Jurkat cells
      transfected with IL-8R1 or IL-8R2 migrate in response to IL-8, GRO alpha and NAP
      2.
AB  - Neutrophil leukocytes, the target cells for interleukin-8 and related CXC
      chemokines, bear high numbers of two types of IL-8 receptors (IL-8R1 and IL-8R2).
      By cDNA transfection Jurkat cell lines were generated that stably express either
      IL-8R1 or IL-8R2 (J-IL8R1 and J-IL8R2). J-IL8R1 expressed 4,000 +/- 1,000 copies
      of IL-8R1, and bound IL-8 with high affinity (Kd 1-4 nM) and GRO alpha and NAP-2
      with low affinity (Kd 200-500 nM). J-IL8R2 expressed 17,000 +/- 3,000 copies of
      IL-8R2, and bound all three chemokines with high affinity. Both transfectants
      showed a similar degree of chemotactic migration after stimulation with IL-8, GRO
      alpha and NAP-2. All three chemokines were equally potent as attractants of J
      IL8R2, whereas IL-8 was 300 to 1,000-fold more potent than GRO alpha or NAP-2 as
      attractant of J-IL8R1. The potencies, therefore, agree with the affinities of the
      ligands to IL-8R1 and IL-8R2. Our results demonstrate that both IL-8 receptors
      function independently, and mediate chemotaxis in response to IL-8 and other CXC
      chemokines.

PMID- 8137939
TI  - Unique cleavage specificity of 'prohormone thiol protease' related to
      proenkephalin processing.
AB  - 'Prohormone thiol protease' (PTP) represents the major enkephalin precursor
      processing activity in chromaffin granules. In this study, cleavage specificity
      of PTP for paired basic and monobasic residues was examined with a series of
      model peptide-MCA (-methylcoumarinamide) substrates. Monobasic peptides were
      cleaved at the COOH- and NH2-terminal sides of the single basic residue. Dibasic
      peptides, however, were preferentially cleaved at the NH2-terminal side of the
      pair, or between the two basic residues, with low cleavage at the COOH-terminal
      side of the pair. Inhibition by the peptide inhibitor (D-Tyr)-Glu-Phe-Lys-Arg
      CH2Cl provided further evidence for PTP's specificity for the dibasic Lys-Arg
      site. Inhibition by Z-Leu-Val-Gly-CHN2 and Z-Arg-Leu-Val-Gly-CHN2 suggests
      involvement of Val-Gly in substrate binding to PTP; these two cystatin C-related
      inhibitors also indicate PTP as a cysteine protease. These results demonstrate
      PTP's unique cleavage specificity that differs from other processing
      endopeptidases, including the subtilisin-related proprotein convertases, PC1/PC3,
      and PC2, as well as the pituitary proopiomelanocortin-converting enzyme, PCE.
      This study provides further evidence for PTP as a novel prohormone processing
      enzyme that belongs to the class of cysteine proteases.

PMID- 8137940
TI  - Protein kinase-C mediates dual modulation of L-type Ca2+ channels in human
      vascular smooth muscle.
AB  - The role of protein kinase C (PKC) in cellular regulation of L-type Ca2+ channels
      was investigated in human umbilical vein smooth muscle. Activation of PKC, by low
      concentrations (< 30 nM) of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) caused
      inhibition of Ca2+ channels, while higher concentrations of TPA (> 100 nM)
      elicited a transient rise, followed by sustained inhibition of Ca2+ channel
      activity in cell-attached patches. Low TPA concentrations predominantly reduced
      channel availability, while high concentrations of TPA (100 nM) transiently
      increased channel availability and, in addition, prolonged mean open time. The
      inactive 4-alpha-phorbol-12,13- didecanoate failed to affect channel activity,
      and pretreatment of the cells with PKC inhibitors (H-7, chelerythrine)
      antagonized inhibitory and stimulatory effects of TPA. Our results provide
      evidence for two distinct PKC-dependent mechanisms of L-type Ca2+ channel
      regulation in smooth muscle.

PMID- 8137941
TI  - Localization of disulfide bridges and free sulfhydryl groups in human eosinophil
      granule major basic protein.
AB  - Eosinophil granule major basic protein (117 residues) is known to contain free
      sulfhydryl groups. Here we have located in the amino acid sequence the half
      cystine residues present as cysteine, and identified those engaged in disulfide
      bridges. Of the 9 half-cystine residues, 5 are unpaired cysteines (Cys2, Cys23,
      Cys42, Cys64, and Cys96), while 4 form disulfides (Cys20-Cys115, and Cys92
      Cys107).

PMID- 8137942
TI  - Radioimmunoassay for circulating human guanylin.
AB  - A highly specific and sensitive radioimmunoassay for circulating human guanylin
      (guanylin-22-115) has been developed. Antibodies were raised against the amino
      terminus (positions 4-16) of the peptide. Western blot analysis confirmed that
      the antibody selected for radioimmunoassay recognizes circulating high molecular
      weight (10.3 kDa) guanylin. Extraction and purification of guanylin from blood
      hemofiltrate and from blood plasma showed that circulating guanylin is detectable
      in corresponding amounts by the radioimmunoassay and by a specific bioassay. In
      30 healthy subjects, the mean plasma concentration of immunoreactive (IR)
      guanylin was 42 +/- 3 fmol/ml. In 22 patients with chronic renal insufficiency,
      the concentrations of IR-guanylin were significantly enhanced (1,074 +/- 24
      fmol/ml), indicating that kidneys metabolize and/or eliminate the circulating
      hormone.

PMID- 8137943
TI  - Yeast cells with a specific cellular make-up and an environment that removes
      acetaldehyde are prone to sustained glycolytic oscillations.
AB  - Glycolytic oscillations can be induced by adding glucose to starved Saccharomyces
      cerevisiae cells and, after a steady state has been established, cyanide.
      Transient oscillations or limit-cycle oscillations can be induced depending on
      the growth phase in which the cells are harvested. To find what causes these
      differences in the dynamic behaviour, we analyzed glycolytic enzyme activities at
      different growth phases. The hexokinase activity increased by a factor of three
      after growth substrate transition from glucose to ethanol; the other measured
      activities remained constant. Cyanide was found not only to block respiration,
      but also to trap acetaldehyde. Both cyanide actions appear necessary for the
      occurrence of sustained glycolytic oscillations.

PMID- 8137944
TI  - Phosphorylation by Ca2+/calmodulin-dependent protein kinase II and protein kinase
      C of sepiapterin reductase, the terminal enzyme in the biosynthetic pathway of
      tetrahydrobiopterin.
AB  - Sepiapterin reductase, the terminal enzyme in the biosynthetic pathway of
      tetrahydrobiopterin, was stoichiometrically phosphorylated by Ca2+/calmodulin
      dependent protein kinase II and protein kinase C (Ca2+/phospholipid-dependent
      protein kinase) in vitro. Maximal incorporation of phosphate into the enzyme
      subunit by these was 3.05 +/- 0.05 (n = 4) and 0.74 +/- 0.03 (n = 5) 32P mol per
      mol enzyme subunit, respectively. The enzyme was not phosphorylated by cyclic
      nucleotide-dependent protein kinase of either the cAMP-dependent or cGMP
      dependent type in this study. Dihydropteridine reductase, another enzyme working
      in direct supply of tetrahydrobiopterin, was also a good substrate for
      Ca2+/calmodulin-dependent protein kinase II. Phosphorylation of sepiapterin
      reductase by these protein kinases modified the kinetic properties of the enzyme.
      It is likely that these multifunctional Ca(2+)-activated protein kinases may play
      a role in the regulation of the physiological function of the BH4-generating
      enzymes in vivo, as was previously found in the case of BH4-requiring enzymes.

PMID- 8137945
TI  - The functional roles of disulfide bonds in the beta-subunit of (Na,K)ATPase as
      studied by site-directed mutagenesis.
AB  - The beta-subunit of Torpedo californica (Na,K)ATPase contains seven cysteine
      residues; one (Cys46) is in the single transmembrane segment and the other six
      (Cys127, Cys150, Cys160, Cys176, Cys215 and Cys278) are in the extracellular
      domain and form three highly conserved disulfide bonds. A beta-subunit mutant
      with replacement of Cys46 by Ser could assemble with the alpha-subunit, and the
      resulting alpha beta-complex was catalytically active. Mutants in which either
      the N-terminal side or both Cys residues of the Cys127-Cys150 bond were replaced
      by Ser could also tightly assemble with the alpha-subunit, but the resulting
      alpha beta-complex was catalytically inactive. On the other hand, disruption of
      either the Cys160-Cys176 or Cys215-Cys278 bond by substituting the N-terminal
      side only or both Cys residues with Ser led to a beta-subunit that could not
      assemble with the alpha-subunit. We conclude that the structure of the beta
      subunit around the Cys160-Cys176 and Cys215-Cys278 loops is indispensable for
      assembly with the alpha-subunit, whereas the Cys127-Cys150 loop is not essential
      for assembly but is required for enzyme activity.

PMID- 8137946
TI  - A porcine gut polypeptide identical to the pancreatic hormone PP (pancreatic
      polypeptide).
AB  - A peptide hormone has been isolated from porcine intestine. Its primary structure
      was found to consist of 36 amino acid residues in a sequence identical to that of
      the porcine pancreatic polypeptide, previously not isolated from intestines or a
      tissue other than pancreas. The gut polypeptide significantly suppresses glucose
      induced insulin secretion in vitro. Using an immunohistochemical technique, we
      also identified cells in the porcine gastrointestinal tract that were
      immunoreactive with pancreatic polypeptide. The immunoreactivity disappeared
      after absorption with the isolated gut polypeptide or synthetic human pancreatic
      polypeptide.

PMID- 8137947
TI  - Effect of sialic acid removal on the antibody response to the third variable
      domain of human immunodeficiency virus type-1 envelope glycoprotein.
AB  - The gp160 envelope glycoprotein of human immunodeficiency virus type-1 (HIV-1) is
      an essential component of current vaccine trials. The glycans of gp160, part of
      which are highly sialylated, have been shown to influence gp160 immunogenicity.
      Here, using a panel of synthetic V3 peptides, we characterized the anti-V3
      antibodies generated in rabbits immunized by desialylated recombinant gp160LAI.
      Amino acid residues flanking the GPGR tip of V3 were necessary for the
      recognition by anti-V3 antibodies raised against either the native or
      desialylated gp160. Both types of antibodies reacted to V3 peptides of MN and SF2
      strains and with a North American/European V3 consensus peptide, while anti
      desialylated gp160LAI antibodies reacted in addition to the V3 of CDC4, WMJ2 and
      NY5 strains. Yet, the V3 peptides did not significantly differ in their secondary
      structure, as determined by circular dichroism. The titer and avidity for V3MN of
      anti-desialylated gp160LAI antibodies were significantly lower than those of anti
      native gp160LAI, which likely accounts for the inability of anti-desialylated
      gp160LAI sera to neutralize HIV-1MN-induced syncytia. These results indicate that
      V3 immunogenicity may be influenced by subtle directed changes in the gp160
      glycosylation pattern.

PMID- 8137948
TI  - A carotenogenic gene cluster exists on a large plasmid in Thermus thermophilus.
AB  - In Thermus thermophilus HB27, the crtB gene encoding phytoene synthase was found
      to exist on the large plasmid, pTT27. One of the carotenoid under-producing
      mutants, Crt31, carried a derivative of pTT27 (pTT27') in which deletion and
      inversion were observed near the crtB gene. T. thermophilus HB8 also contained a
      large plasmid which showed homology to pTT27 and the crtB gene. These results
      suggested that genes for carotenoid biosynthesis occurred as a cluster on a large
      plasmid in Thermus thermophilus. This is the first report to show directly that
      carotenogenesis is plasmid-encoded in microorganisms.

PMID- 8137949
TI  - The oxidation of low density lipoprotein by cells or iron is inhibited by zinc.
AB  - We have examined the effect of zinc ions on low density lipoprotein (LDL)
      oxidation by macrophages, endothelial cells and iron ions in terms of the
      increased uptake of the LDL by macrophages. Zinc ions inhibited LDL modification
      by both cell types (which is dependent on the presence of iron ions in the
      culture medium) and by iron ions alone. As oxidised LDL is believed to be
      involved in atherogenesis, this raises the possibility that zinc may be an
      endogenous protective factor against atherosclerosis.

PMID- 8137950
TI  - Ascorbic acid can either increase or decrease low density lipoprotein
      modification.
AB  - In freshly prepared low density lipoprotein (LDL), ascorbate inhibited LDL
      oxidation by macrophages at the higher concentrations tested (60-100 microM). In
      contrast, with LDL that had been allowed to autoxidise in the refrigerator (3
      degrees C) for at least 10 weeks after isolation (mildly oxidised or minimally
      modified LDL), ascorbate did not inhibit the modification of LDL in the presence
      of macrophages. Ascorbate actually modified autoxidised LDL itself in the absence
      of macrophages to greatly increase its uptake by macrophages. The modification of
      autoxidised LDL by ascorbate increased the levels of thiobarbituric acid-reactive
      substances in the medium and was completely inhibited by the antioxidant
      butylated hydroxytoluene. Thus the effects of ascorbate on unoxidized LDL can be
      very different to those on mildly oxidised LDL.

PMID- 8137951
TI  - Immunocytochemical localization of Ca(2+)-dependent protease from Allomyces
      arbuscula.
AB  - The Ca(2+)-dependent protease antisera and the purified specific antibodies from
      Allomyces arbuscula have shown very specific recognition when blotted against the
      total protein extract or the purified 43-40 kDa Ca(2+)-dependent protease from
      this aquatic fungus. By immunoblotting and immunofluorescence techniques using
      specific antibodies, we have shown that the enzyme activity is developmentally
      regulated and is related to the presence of antigen and not to any specific
      inhibitor. The immunofluorescence was absent in zoospores but appeared in
      polarized forms in germinating spores. In elongating hyphae the protease was
      mainly localized along the cytoplasmic membrane and in the cytoplasm, with
      predominance at the apex.

PMID- 8137952
TI  - Effect of glutathione depletion on formation of paramagnetic chromium in Chinese
      hamster V-79 cells.
AB  - Incubation of Chinese hamster V-79 cells with either buthionine sulfoximine (BSO)
      or diethylmaleate (DEM) prior to exposure to Na2CrO4 resulted in a depletion of
      GSH. ESR study shows that the depletion of GSH by BSO caused an increase in the
      cellular level of Cr(V) intermediate without affecting the level of Cr(III)
      complex, whereas the levels of Cr(V) and (III) were both suppressed by the
      depletion of GSH by DEM. GSH depletion by DEM decreased cellular uptake of
      chromate more than that by BSO. Glutathione reductase activity in cells, which is
      capable of reducing Cr(VI), was unaffected by BSO, however a strong inhibition
      was observed in cells treated with DEM, indicating that DEM affects not only GSH
      levels but also Cr(VI)-reducing enzyme activity. Thus, the depletion of GSH in
      cells increases Cr(V) formation, based upon the effect of BSO. The role of
      intracellular GSH in Cr(VI) reduction is discussed.

PMID- 8137953
TI  - Aequorea green fluorescent protein. Expression of the gene and fluorescence
      characteristics of the recombinant protein.
AB  - Expression of the cDNA for Aequorea green fluorescent protein in E. coli yielded
      a fused protein with fluorescence excitation and emission spectra virtually
      identical to those of the native green fluorescent protein. Further, a solution
      of the protein, when mixed with aequorin and calcium ion, emitted a greenish
      luminescence characteristic of the in vivo luminescence of the animal, indicating
      a radiationless energy transfer to the protein.

PMID- 8137954
TI  - The membrane proteins TRAMp and sec61 alpha p may be involved in post
      translational transport of presecretory proteins into mammalian microsomes.
AB  - The presecretory protein ppcecDHFR, a hybrid between preprocecropinA and
      dihydrofolate reductase, is transported into mammalian microsomes post
      translationally, i.e. independent of ribosome and signal recognition particle.
      Here, the involvement of microsomal proteins in ribonucleoparticle-independent
      transport of ppcecDHFR was analyzed by transport into trypsin-pretreated
      microsomes and by transport of a truncated version of ppcecDHFR and subsequent
      chemical cross-linking. We observed that post-translational transport of
      ppcecDHFR can occur into microsomes which had been pretreated with trypsin (final
      concentration, 100 micrograms/ml) and that of the known transport components only
      TRAMp and sec61 alpha p are still present under these conditions. Furthermore, we
      found that the truncated ppcecDHFR, ppcecDHFR-98mer', can be cross-linked to 36
      kDa microsomal membrane proteins during post-translational transport. Therefore,
      the two microsomal membrane proteins with molecular masses of about 36 kDa, TRAMp
      and sec61 alpha p, appear to be involved in the post-translational transport of
      ppcecDHFR and ppcecDHFR-98mer.

PMID- 8137955
TI  - Immunoreactive adrenomedullin in human plasma.
AB  - A specific and sensitive radioimmunoassay for adrenomedullin has been developed.
      Half-maximal inhibition of binding of radioiodinated adrenomedullin was observed
      at 4 fmol/tube. The radioimmunoassay recognized the entire adrenomedullin
      molecule and has little crossreactivity with adrenomedullin fragment peptides.
      Adrenomedullin-like immunoreactivity was found to circulate in human plasma at
      considerable concentration (3.3 +/- 0.39 fmol/ml). The immunoreactivity of
      adrenomedullin was eluted at almost the same position as synthetic adrenomedullin
      on gel-filtration chromatography and reverse-phase high-performance liquid
      chromatography, suggesting that circulating adrenomedullin recognized by the
      present radioimmunoassay is identical or very similar to authentic
      adrenomedullin. Plasma immunoreactive adrenomedullin significantly increased in
      patients with hypertension, with a progressive rise proportionate to disease
      severity.

PMID- 8137956
TI  - A novel prenyltransferase, farnesylgeranyl diphosphate synthase, from the
      haloalkaliphilic archaeon, Natronobacterium pharaonis.
AB  - A novel prenyltransferase, farnesylgeranyl diphosphate (FGPP) synthase (EC
      2.5.1.X), which synthesizes C25-prenyl diphosphate, was found in the
      haloalkaliphilic archaeon Natronobacterium pharaonis. It was separated from
      geranylgeranyl diphosphate (GGPP) synthase (EC 2.5.1.29), which synthesizes C20
      prenyl diphosphate, a major prenyltransferase in this organism. The highest
      activity of FGPP synthase was observed when GGPP was used as the allylic
      substrate. FGPP synthase may synthesize a precursor for the C25 moiety of C20,
      C25 diether lipids using a longer allylic diphosphate, such as GGPP synthesized
      by GGPP synthase, rather than dimethylallyl diphosphate, which is the product of
      isopentenyl diphosphate isomerase.

PMID- 8137957
TI  - Changes of the expression of protein substrates of Ca2+/calmodulin-dependent
      protein kinase II in neonate and adult rats.
AB  - We studied the expression of whole protein substrates of Ca2+/calmodulin
      dependent protein kinase II (CaM kinase II) in the forebrain of neonate and adult
      rats. Protein substrates were determined by phosphorylation of the soluble and
      particulate fractions by CaM kinase II with [gamma-33P]ATP. Phosphorylated
      proteins were analyzed by SDS-PAGE and two-dimensional gel electrophoresis. More
      than 50 endogenous proteins were found to be phosphorylated by CaM kinase II in
      both soluble and particulate fractions. The expression of about 15 protein
      substrates increased in the particulate fraction from neonate to adult rats, and
      that of several proteins also changed in the soluble fraction. These findings
      suggest that the expression of protein substrates was regulated during
      development as well as that of CaM kinase II itself.

PMID- 8137958
TI  - Molecular cloning, functional expression and localization of a novel inward
      rectifier potassium channel in the rat brain.
AB  - We have cloned a novel inward rectifier potassium channel from a rat brain cDNA
      library and designated it RB-IRK2. The rat brain cDNA library was screened using
      a fragment of the mouse macrophage IRK1 cDNA as a probe. The amino acid sequence
      of RB-IRK2 shares 70%, 40% and 45% identity to mouse IRK1, rat ROMK1 and rat
      GIRK1, respectively. Xenopus oocytes injected with cRNA derived from RB-IRK2
      expressed a potassium current which showed inward-rectifying channel
      characteristics similar to the IRK1 current, but distinct from the ROMK1 or the
      GIRK1 currents. However, the localization of RB-IRK2 mRNA in rat tissues,
      assessed by the Northern blot analysis, differed from that of mouse IRK1. These
      results indicate that the IRK family is composed of multiple genes, which express
      in different tissues and therefore may play heterogenous functional roles in
      various organs, including rat central nervous system.

PMID- 8137959
TI  - Complications of assisted reproductive techniques.
AB  - OBJECTIVE: To review and appreciate the relevant data on assisted reproduction
      techniques and their potential complications. DATA RESOURCES: Major publications
      on assisted reproduction that include the information concerning complications
      associated with this practice. RESULTS: Assisted reproduction is a common
      practice in modern reproductive medicine. Complications are associated with
      ovulation induction and the extracorporeal methods that are used for IVF-ET,
      GIFT, and zygote intrafallopian transfer (ZIFT). These complications are
      associated with laparoscopy, anesthesia, oocyte retrieval, and laboratory
      facilities. Pregnancies resulting from assisted reproduction are more complicated
      than spontaneous pregnancies. There are higher rates of ectopic, heterotopic, and
      multifetal pregnancies; abortions; and premature deliveries. Increased rates of
      perinatal mortality and morbidity result from prematurity, and higher rates of
      maternal diseases in pregnancy (preeclampsia, diabetes mellitus, bleeding,
      anemia) contribute to fetal intra-uterine growth restriction and maternal
      morbidity. CONCLUSIONS: Assisted reproduction practice should be well controlled
      in view of the potential for complications before and during pregnancies.

PMID- 8137960
TI  - On attempts at cloning in the human.

PMID- 8137961
TI  - Treatment of hirsutism with a gonadotropin-releasing hormone agonist and estrogen
      replacement therapy.
AB  - OBJECTIVE: To determine the efficacy of treatment of significant hirsutism with a
      GnRH agonist (GnRH-a) and estrogen and progestin replacement therapy. DESIGN:
      Clinical series. SETTING: Ambulatory gynecology clinic in a community hospital.
      PATIENTS: Ten women with significant hirsutism caused by polycystic ovarian
      disease. INTERVENTIONS: The patients were treated with leuprolide acetate 20
      micrograms/kg per day in combination with E2 (2 mg) and medroxyprogesterone
      acetate (5 mg) for 6 months. MAIN OUTCOME MEASURE: Hirsutism scores and hair
      growth rates determined before and upon completion of treatment protocol.
      RESULTS: Hirsutism scores and hair growth rates significantly decreased by 23%
      and 26%, respectively. The duration of hirsutism was the only significant
      covariate for hirsutism scores and hair growth rates. Only two patients had
      minimal, irregular bleeding that was corrected by increasing the estrogen dose.
      CONCLUSION: The combination of a GnRH-a and estrogen replacement therapy was an
      effective and well-tolerated treatment in a small group of women with significant
      hirsutism caused by PCOD.

PMID- 8137962
TI  - The hypothalamic-pituitary-ovarian axis in patients with endometriosis is
      suppressed by leuprolide acetate but not by danazol.
AB  - OBJECTIVE: To investigate the effects of leuprolide acetate (LA), a GnRH agonist
      (GnRH-a), and of danazol on the hypothalamic-pituitary-ovarian axis in patients
      with endometriosis. DESIGN: Ten patients were divided into LA and danazol
      treatment groups. MEASURES: Serum levels of E2, immunoreactive and bioactive LH,
      pulsatility of LH, and gonadotropins release by GnRH. Changes in serum E2 levels
      by hMG administration during LA treatment. RESULTS: Serum E2 level decreased to
      near castrated levels during the LA treatment, while it remained unchanged during
      the danazol treatment. Leuprolide acetate administration resulted in a
      significant suppression of the serum level of bioactive LH, of the pulsatility of
      LH release, of the pituitary response to GnRH injection, and of the elevation in
      the serum E2 level by hMG administration, but danazol treatment did not show
      these suppressive effects. CONCLUSION: Our results suggest that the hormonal
      actions of LA and danazol on endometriosis are different from each other,
      especially in the suppression of serum E2 level.

PMID- 8137963
TI  - Serum and peritoneal fluid CA-125 levels in patients with endometriosis.
AB  - OBJECTIVE: To evaluate CA-125 in peritoneal fluid (PF) as an indicator of
      endometriosis. DESIGN: CA-125 levels in paired serum and PF were determined by
      the one-step immunoradiometric assay. For peritoneal samples, high dilution of
      the sample (1:100) was used to avoid false low results, caused by the "hook
      effect" phenomenon. PATIENTS: Forty-one women with and without endometriosis,
      undergoing laparoscopy or laparotomy during the follicular phase of the menstrual
      cycle, were selected. SETTING: 2nd Institute of Obstetrics and Gynecology,
      University of Rome "La Sapienza," Rome, Italy. MAIN OUTCOME MEASURE: Peritoneal
      fluid CA-125 levels obtained using diluted samples were significantly higher than
      those found using undiluted ones. RESULTS: CA-125 levels in PF were approximately
      100 times higher than those found in paired serum, ranging from 970 to 10,636
      U/mL. In patients with endometriosis, CA-125 levels in PF were significantly
      elevated when compared with the control group. In serum, CA-125 levels increased
      only in advanced stages of endometriosis. CONCLUSIONS: The sensitivity of the CA
      125 test for endometriosis in PF is greater than in serum. Therefore, the
      measurement of CA-125 levels in PF could be useful in the detection of early
      stage endometriosis, which tends to be overlooked by the CA-125 serum test.

PMID- 8137964
TI  - Timing of the endometrial biopsy may be critical for the accurate diagnosis of
      luteal phase deficiency.
AB  - OBJECTIVE: To determine the optimal time to perform the endometrial biopsy for
      the detection of "out-of-phase" endometrium. DESIGN: Two endometrial biopsies
      were performed during a single menstrual cycle in each subject. The patient's
      chronological day was determined by counting forward from the midcycle LH surge,
      as assessed by urinary LH detection. The "early" biopsy was done on day LH + 7.4
      +/- 0.8, and the "late" biopsy on day LH + 11.6 +/- 0.7. Each biopsy was
      independently read by two pathologists and was considered out of phase if the
      histologic date was > or = 3 days delayed compared with the chronological date.
      SETTING: Infertility practice of an academic teaching hospital. PATIENTS: Thirty
      three ovulatory women seeking evaluation for infertility. MAIN OUTCOME MEASURE:
      Number of patients with out-of-phase endometrium detected by the early versus the
      late biopsy. RESULTS: There was a significantly greater detection rate for out-of
      phase endometrium using the early biopsy (12.1% to 18.2% incidence depending on
      the observer) compared with the later biopsy (6.1% to 9.1% incidence). A majority
      of the early out-of-phase biopsies corrected by the time of the later biopsy.
      CONCLUSION: Our findings indicate that an endometrial biopsy performed in the
      midluteal phase may detect a greater number of women with delayed endometrial
      maturation during the temporal window of embryo implantation. The observation
      that most of the women with out-of-phase midluteal biopsies had normal late
      luteal endometrium may represent a cryptic form of luteal phase deficiency.

PMID- 8137965
TI  - Reference values for luteal progesterone measured by salivary radioimmunoassay.
AB  - OBJECTIVE: To establish age-stratified reference values for salivary luteal P
      levels. DESIGN: One hundred thirty-six regularly menstruating women (18 to 48
      years of age), screened for weight, exercise, and steroid medication use,
      collected daily saliva samples for one complete menstrual cycle. Luteal P levels
      were measured by 3H-RIA, and data were aligned by day of next menstrual onset.
      Means (+/- 1 SD range) and percentiles, calculated using both untransformed and
      log transformed data, were calculated for each luteal day and for indices of
      luteal P production. RESULTS: Reference values for salivary daily luteal P levels
      and indices of luteal P are presented for three age groups (18 to 24 years, 25 to
      39 years, and 40 to 48 years). CONCLUSION: The age-stratified reference values
      presented here can be used, without collateral clinical procedures, to assess
      salivary luteal P levels. Salivary monitoring is ideally suited for research and
      long-term clinical observation, but the characteristics of salivary P data may
      limit the usefulness of these values for individual diagnosis.

PMID- 8137966
TI  - Hemostatic and metabolic variables in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To study whether a previously demonstrated increased morbidity in
      cardiovascular disease (CVD) and diabetes mellitus in women with polycystic ovary
      syndrome (PCOS) is associated with certain hemostatic variables that are known to
      be markers for CVD. DESIGN: The study was a trans-sectional follow-up study from
      a cohort of women with PCOS. SETTING: The women with PCOS were recruited from
      hospital clinics and referents were randomized from a population study of women
      from the same area. PARTICIPANTS: The investigation involved 28 women aged 43 to
      62 years diagnosed to have PCOS on ovarian histopathology at wedge resection 25
      to 34 years previously and 56 referents who were matched by age and body mass
      index. MAIN OUTCOME MEASURES: In connection with a clinical investigation, the
      hemostatic variables fibrinogen, von Willebrand factor antigen, factor VII
      procoagulant activity, factor VII antigen, and plasminogen activator inhibitor as
      well as the metabolic variables serum insulin and serum triglycerides were
      assayed. RESULTS: There was a strong positive correlation between serum
      concentrations of triglyceride, basal insulin, and abdominal obesity on the one
      hand, and plasminogen activator inhibitor, fibrinogen, and von Willebrand factor
      on the other, among women with PCOS as well as among referents. There were
      significantly higher mean concentrations of fibrinogen and factor VII:Ag among
      referents, but the mean values of most hemostatic variables studied showed no
      differences between the groups. CONCLUSION: Women with an altered metabolic
      profile were also found to have affected hemostatic factors, but PCOS in itself
      did not seem to influence them.

PMID- 8137967
TI  - Salpingoscopic findings in women with occlusive and nonocclusive salpingitis
      isthmica nodosa.
AB  - STUDY OBJECTIVE: To characterize ampullary endosalpingeal findings in women with
      occlusive or nonocclusive salpingitis isthmica nodosa. DESIGN: Prospective case
      study. SETTING: Obstetrics and Gynecology Department of a University Hospital.
      PATIENTS: Twenty women (38 tubes) with occlusive or nonocclusive salpingitis
      isthmica nodosa were studied. INTERVENTIONS: Salpingoscopy was performed during
      diagnostic laparoscopy in 20 women (38 tubes) with hysterosalpingographic
      evidence of salpingitis isthmica nodosa. MAIN OUTCOME MEASURES: Salpingoscopic
      findings were recorded and the patients were managed accordingly. RESULTS: Of the
      38 tubes 10 appeared radiographically and laparoscopically normal. Two tubes were
      occluded distally. Of the 26 tubes with occlusive or nonocclusive salpingitis
      isthmica nodosa, 5 (19.2%) showed varying degrees of endosalpingeal abnormality.
      Patients with abnormal salpingoscopy were regarded as having bipolar tubal
      disease and were referred for assisted conception. The remaining patients were
      scheduled for microsurgical tubal reconstruction. CONCLUSIONS: One in five
      patients with proximal tubal disease may have ampullary endosalpingeal damage of
      varying degrees. However, the significance of this finding in relation to
      subsequent management strategies and fertility outcome is yet to be
      characterized.

PMID- 8137968
TI  - Comparison of fallopian tube intraluminal pathology as assessed by salpingoscopy
      with pelvic adhesions.
AB  - OBJECTIVE: To correlate the severity and extent of pelvic adhesions, as noted at
      laparotomy for microsurgery, with the presence and extent of fallopian tube
      intraluminal pathology, as noted using salpingoscopy. DESIGN: Prospective
      clinical study. SETTING: A university teaching hospital. PATIENTS: Twenty
      patients presenting for pelvic microsurgery between July 1992 and January 1993.
      INTERVENTIONS: Salpingoscopy was performed at the time of microsurgery and
      intraluminal pathology was scored. An objective assessment of the extent of
      pelvic adhesions was made using standardized adhesion score systems. RESULTS:
      There was a strong correlation between the degree of intratubal damage and the
      extent of pelvic adhesions when the etiology was previous pelvic inflammatory
      disease (PID) but not when the underlying etiology was endometriosis. However, in
      the endometriosis subgroup, intraluminal ampullary pathology was noted in 27% of
      tubes assessed, and intraluminal fimbrial pathology was noted in 36% of tubes
      assessed. Intraluminal tubal pathology also was noted in a number of cases where
      the underlying etiology was previous surgery for benign disease. CONCLUSIONS:
      This study confirms previous reports that, in cases of PID leading to adhesions,
      there is a high incidence of intraluminal pathology. However, this study also
      demonstrates that intraluminal pathology is often associated with adhesions
      arising from other etiologic groups, suggesting that intraluminal assessment is
      required for all patients in whom adhesiolysis for fertility is considered.

PMID- 8137969
TI  - A meta-analysis of the therapeutic role of oil soluble contrast media at
      hysterosalpingography: a surprising result?
AB  - OBJECTIVE: To evaluate the therapeutic effect of oil-soluble contrast media
      compared with water-soluble contrast media after hysterosalpingography (HSG) in
      infertile couples. DESIGN: Meta-analysis of four randomized clinical trials
      (RCTs) and six nonrandomized controlled studies evaluating pregnancy rates after
      the use of oil- or water-soluble contrast media during HSG. SETTING: Institute of
      Epidemiology and Health Services Research, Leeds, United Kingdom. PATIENTS: Four
      identified RCTs studied 800 patients and six nonrandomized studies comprised an
      additional 1,806 patients, all experiencing primary or secondary infertility.
      INTERVENTION: Hysterosalpingography as part of infertility investigation. MAIN
      OUTCOME MEASURE: Pregnancy rates after HSG. RESULTS: Pregnancy rates were
      significantly higher in the oil-soluble contrast media group compared with the
      water-soluble contrast media group in the RCTs. Inclusion of the six
      nonrandomized studies did not alter this conclusion. This apparent benefit was
      greatest for patients with unexplained infertility. CONCLUSIONS: Oil-soluble
      contrast media have a therapeutic effect compared with water-soluble media and
      this effect is greatest for patients who have been diagnosed as having
      unexplained infertility. New techniques for the evaluation of tubal patency
      support the hypothesis that tubal "plugs" may be involved in proximal tubal
      blockage.

PMID- 8137970
TI  - Identification of main risk factors for tubal infertility.
AB  - OBJECTIVE: To determine the relationship between some reproductive variables and
      infertility caused by tubal obstruction. DESIGN: A retrospective, case-control
      study. SETTING: A tertiary care university hospital that is a referral center for
      infertility patients. PARTICIPANTS: Subjects were interviewed between March 1990
      and December 1991. Cases were 215 consecutively recruited infertile women with
      either evidence of tubal obstruction found at laparoscopy or hydrosalpinx
      diagnosed by hysterosalpingography. Women with a history of surgical
      sterilization were excluded. Controls, selected in the same hospital, were women
      in the puerperium who had no history of infertility. Two controls were matched by
      age at the time of tubal obstruction diagnosis to each case. RESULTS: History of
      pelvic surgery and use of alcohol were significantly associated with the risk of
      infertility caused by tubal obstruction. The use of barrier, oral, and
      medroxyprogesterone acetate (MPA) contraceptives was associated with a protective
      effect. When only women with secondary infertility were analyzed, history of
      pelvic surgery and number of lifetime sexual partners were significant risk
      factors, and the previous use of oral contraceptives was the only protective
      factor. CONCLUSIONS: History of pelvic surgery was the most important risk factor
      for tubal infertility. All precautions must be taken to avoid infection and
      adhesion formation when pelvic surgery is performed. In addition, women can be
      protected from tubal infertility by using barrier, oral, or MPA contraceptive
      methods.

PMID- 8137971
TI  - Insulin-like growth factor-II stimulates human granulosa-luteal cell
      proliferation in vitro.
AB  - OBJECTIVE: To determine the effect of insulin-like growth factor-II (IGF-II) on
      human granulosa cell proliferation in vitro. DESIGN: Thymidine incorporation and
      cell count were determined to assess human granulosa cell proliferation. SETTING:
      The study was performed in an academic research environment. PATIENTS: Granulosa
      cells were obtained from women undergoing IVF procedures. INTERVENTIONS:
      Granulosa cells were dispersed enzymatically and cultured in both serum
      containing and serum-free medium. MAIN OUTCOME MEASURE: Granulosa cell
      proliferation in basal conditions and after stimulation with IGF-II given alone
      or in combination with basic fibroblast growth factor (basic FGF). RESULTS:
      Treatment of human granulosa cells with IGF-II for 24 hours significantly
      increased thymidine incorporation. Furthermore, this mitogenic effect was
      confirmed when granulosa cells were cultured in presence of IGF-II for 7 to 10
      days and their proliferation was evaluated by cell counting. The association of
      IGF-II and basic FGF did not result in a synergistic or additive effect.
      CONCLUSION: As already demonstrated in other species, IGF-II also is able to
      stimulate human granulosa cell proliferation in vitro. Thus, it might be
      considered among the intraovarian modulators of granulosa cell physiology.

PMID- 8137972
TI  - Localization of leukocyte subsets in the follicle wall and in the corpus luteum
      throughout the human menstrual cycle.
AB  - OBJECTIVE: To determine the presence and localization of leukocyte subsets in the
      human follicular wall and in the corpus luteum (CL) throughout the menstrual
      cycle. DESIGN: Tissue was obtained by biopsy at laparoscopy. Frozen sections were
      labeled with a panel of monoclonal antibodies against leukocyte subtype markers
      and detected by immunohistochemical methods. SETTING: Infertility clinic in large
      teaching hospital. PATIENTS: Eighteen women who underwent diagnostic laparoscopy.
      Women with abnormal endocrinology, endometriosis, or ovarian disease were
      excluded. RESULTS: Macrophages and neutrophilic granulocytes were present in high
      numbers in the collagen-rich tissues, including the thecal layer, of the follicle
      wall. At ovulation, there was a marked increase in the density of these cells in
      the follicle wall, especially in the thecal layer. In the CL, there was a higher
      density of macrophages (2- to 3-fold) and neutrophils (3- to 5-fold) in the theca
      lutein area compared with the granulosa lutein area. There were no significant
      changes in the density of these cell types when early and late luteal phase were
      compared, but the density of macrophages were markedly elevated in regressing CLs
      obtained during the subsequent follicular phase. T lymphocytes were present in
      low numbers in the follicle wall and in the CL, and no variation in the density
      was detected throughout the menstrual cycle. CONCLUSION: Macrophages and
      neutrophilic granulocytes are present in high numbers in the follicle wall and
      are further increased in the theca at ovulation, suggesting an active role for
      these leukocyte subtypes in tissue remodeling during the ovulatory process.
      Macrophages and neutrophils are also abundant in the CL, and an increase in the
      macrophage density at CL regression could imply a role for these cells in
      luteolysis.

PMID- 8137974
TI  - Frozen zygote intrafallopian transfer: a successful approach for transfer of
      cryopreserved embryos.
AB  - OBJECTIVE: To assess whether frozen ET to the fallopian tube is a possible
      alternative for cryopreserved embryos. DESIGN: Fifty-four patients (mean age 35
      years) participated, in which their embryos were cryopreserved in 1.5 M
      propanediol at the pronuclear or two-cell stage. Each patient then underwent a
      steroid replacement cycle consisting of oral micronized 17 beta-E2 2 mg on days 2
      to 4, 4 mg on days 5 to 7, 6 mg on days 8 to 10, and 8 mg from day 11 on. Serial
      ultrasounds were performed to evaluate the endometrium until an optimal thickness
      of > or = 10 mm triple layer was achieved. At this time, 100 mg IM progesterone
      was initiated and the zygote intrafallopian transfer (ZIFT) procedure was
      performed on the third day of P administration. The average number of embryos
      transferred was 4.4. RESULTS: Twenty-two clinical pregnancies resulted, giving a
      pregnancy rate of 41%. Eight miscarriages occurred and one ectopic pregnancy
      resulted, giving a live birth rate of 24%. Implantation rate was 10.8%. The
      highest chance of pregnancy was seen in patients who never had a previous IVF,
      GIFT, or ZIFT (61%). CONCLUSION: This is the first report of a series of frozen
      ETs to the fallopian tubes. These results indicate that tubal transfer may offer
      a protective benefit of the tubal environment and avoidance of endometrial
      trauma, and should be added to our armamentarium of replacing cryopreserved
      embryos.

PMID- 8137973
TI  - Expression and potential function of the c-mos proto-oncogene in human eggs.
AB  - OBJECTIVE: To investigate the expression and possible function of the c-mos proto
      oncogene in human eggs. DESIGN: Eggs obtained as discarded material from assisted
      reproductive technology procedures were analyzed for c-mos messenger RNA by
      reverse transcriptase-polymerase chain reaction. As an approach to investigating
      c-mos function, we measured maturation-promoting factor (MPF) activity (histone
      H1 kinase) in eggs without and with inhibition of protein synthesis. Detection of
      RNA transcripts of c-raf was included as control. RESULTS: Transcripts of c-mos
      were detected in small fractions of individual eggs, indicating that c-mos is
      abundantly transcribed. Inhibition of protein synthesis resulted in loss of MPF,
      leading to chromatin decondensation and reformation of a nucleus. C-raf maternal
      messages were also detectable in individual human eggs. CONCLUSION: The c-mos
      proto-oncogene is an abundant maternal message in human eggs as in other species.
      The effects of inhibiting protein synthesis in human eggs are similar to those
      obtained in mouse and Xenopus eggs, either as a consequence of protein synthesis
      inhibition or specific ablation of c-mos RNA by injection of anti-sense
      oligonucleotides. The c-mos gene product is thus likely to play a critical role
      in human oocyte meiosis by regulating the activity of MPF.

PMID- 8137975
TI  - Elevated serum progesterone levels on the day of human chorionic gonadotropin
      administration in in vitro fertilization cycles do not adversely affect embryo
      quality.
AB  - OBJECTIVE: To assess the effect of an elevated serum P level on the day of hCG
      administration in an IVF cycle on resulting embryos by evaluating their
      performance at subsequent frozen ET. DESIGN: A retrospective study. PARTICIPANTS:
      Ninety-six consecutive patients undergoing frozen ET cycles were studied in a
      tertiary care center. MAIN OUTCOME MEASURES: Serum obtained on the day of hCG
      administration in an IVF cycle was assayed for E2 and P by RIA. The main outcome
      measured was the development of a clinical pregnancy in a subsequent frozen ET
      cycle. RESULTS: Using a previously described breakpoint in serum P concentration
      of 0.9 ng/mL (2.86 nmol/L), 8 of 69 (11.6%) frozen ETs in which embryos from low
      P level IVF cycles were transferred and 7 of 27 (25.9%) frozen ETs of embryos
      from elevated P level IVF cycles were transferred resulted in the development of
      clinical pregnancies. Although this does not clearly demonstrate superiority of
      embryos obtained from elevated P cycles, employing a power calculation, the
      probability that the pregnancy rate in the elevated serum P group is at least
      equal to the observed rate in the low P group is 92.8%. CONCLUSION: These data
      suggest that an elevated serum P level on the day of hCG administration does not
      adversely affect the quality of oocytes or resulting embryos.

PMID- 8137976
TI  - Micromanipulation of human embryos to assist hatching.
AB  - OBJECTIVE: To determine the effects of zona slitting and subsequent embryo
      transfer performed on different days of in vitro human embryonic development to
      allow appropriate application of assisted hatching techniques to clinical IVF-ET.
      DESIGN: A microsurgical technique was used to make a standardized slit in the
      zona pellucida of bipronucleate human embryos on day 2, 3, or 5 after oocyte
      retrieval. A mock ET was performed after the procedure and the rate of blastocyst
      formation and the process of hatching in each embryo was monitored. SETTING: All
      embryos used were donated for research by patients attending the IVF Unit at the
      John Radcliffe Hospital, Oxford, United Kingdom. MAIN OUTCOME MEASURES: The
      effects of the mock ET on the integrity of zona-slit embryos was documented. The
      embryos were cultured further and parameters such as blastocyst formation,
      initiation, and completion of hatching were monitored in all three groups of
      embryos. RESULTS: The mock ET did not have a detrimental effect on embryos as
      assessed by their morphology and subsequent blastocyst formation rate. The
      technique used in this study to make an opening in the zona increased the rate
      and number of blastocysts hatching in all three groups compared with
      nonmanipulated controls. However, the day on which the slit was made did not
      significantly alter the outcome. CONCLUSION: A gap in the zona pellucida of human
      embryos significantly increases the rate of hatching. Micromanipulative
      techniques such as zona slitting can be suitably used for this purpose without
      loss of blastomeres through the gap in the zona or trapping of the embryo during
      the process of hatching.

PMID- 8137978
TI  - Acute pelvic inflammatory disease after oocyte retrieval: adverse effects on the
      results of implantation.
AB  - OBJECTIVE: To determine the impact of pelvic inflammation on the results of IVF
      after oocyte retrieval. DESIGN: Retrospective analysis of IVF cycles. SETTING:
      IVF Unit, Golda Medical Center, Petah Tikva, Israel. PATIENTS: Twenty-eight women
      with a diagnosis of pelvic inflammatory disease (PID) during IVF therapy. MAIN
      OUTCOME MEASURE: The pregnancy rate (PR) of IVF cycles complicated by PID after
      oocyte retrieval was compared with our ongoing IVF results. RESULTS: All 28 women
      with PID during IVF treatment did not conceive, despite the high number of
      oocytes retrieved, fertilized, and transferred. The PR over the same period was
      23% to 31%. CONCLUSIONS: Pelvic infection after IVF treatment might have a
      detrimental effect on the results of treatment. In an effort to maximize the
      chances for normal implantation, postponement of ET should be considered when
      pelvic infection or inflammation is diagnosed.

PMID- 8137977
TI  - Comparison of results after in vitro fertilized human embryos are cultured in
      routine medium and in coculture on Vero cells: a randomized study.
AB  - OBJECTIVE: To investigate whether coculture of human embryos on Vero cells
      improves embryo viability compared with a routine culture method. SETTING: In
      vitro fertilization Clinic of the Hopital Cantonal Universitaire de Geneve,
      Geneva, Switzerland. PATIENT SELECTION: Couples who had given informed consent,
      had undergone < 3 IVF cycles with ET and where the male had normal semen
      parameters were selected. Patients who had undergone > or = 3 IVF cycles with ET
      were allocated directly to coculture. DESIGN: Patients were randomly allocated to
      have their embryos cultured in a routine embryo culture medium or in coculture
      with Vero cells. RESULTS: There was no difference in pregnancy rates between the
      two culture groups. Coculture gave a high (> 50%) rate of blastocyst formation.
      In 16 cycles where patients had previously undergone > or = 3 IVF cycles 4
      patients became pregnant. CONCLUSIONS: Coculture provides no benefit for patients
      that are performing their initial treatment cycles in IVF.

PMID- 8137979
TI  - Most living acrosome-reacted spermatozoa do not fuse with the oocyte when
      inserted into the perivitelline space.
AB  - OBJECTIVE: To evaluate the frequency with which acrosome-reacted spermatozoa fuse
      with the oocyte after subzonal insemination (SUZI). DESIGN: The acrosome reaction
      frequency determined in sperm suspensions used for SUZI was related with the
      frequency of sperm-oocyte fusion after the microinsemination procedure. In some
      experiments, the acrosome reaction frequency was compared in sperm suspensions
      aspirated into the microinjection needle and in those leaving the needle.
      SETTING: Private hospital, public research center, and university-based
      laboratory. PATIENTS, PARTICIPANTS: Patients involved in a program of
      micromanipulation-assisted fertilization and healthy sperm donors. INTERVENTIONS:
      IVF-ET. MAIN OUTCOME MEASURES: Frequency of the acrosome reaction, frequency of
      sperm-oocyte fusion. RESULTS: The procedure of sperm aspiration to the
      microinjection needle followed by active swim-out of motile spermatozoa did not
      change the overall percentage of acrosome-reacted spermatozoa even though the
      subpopulation of acrosome-reacted spermatozoa leaving the needle was enriched in
      recently reacted cells. The frequency of sperm-oocyte fusion was considerably
      lower than the frequency of the acrosome reaction in both patient and donor sperm
      samples, irrespective of the number of spermatozoa inserted per egg. CONCLUSIONS:
      A spontaneous acrosome reaction does not necessarily predispose a spermatozoon to
      fuse with the oocyte after SUZI. It remains to be elucidated whether this
      relative inefficiency of acrosome-reacted spermatozoa is related to technical
      aspects of SUZI or whether, in a more general sense, the acrosomal exocytosis and
      the development of sperm-oocyte fusion capacity are distinctly regulated, though
      closely related, phenomena.

PMID- 8137980
TI  - The zona pellucida-induced acrosome reaction of human spermatozoa is mediated by
      protein kinases.
AB  - OBJECTIVE: To determine if the solubilized human zona pellucida (ZP)-induced
      acrosome reaction is mediated by protein kinases. DESIGN: Capacitated spermatozoa
      were incubated with inhibitors of cyclic adenosine 3':5'-monophosphate (cAMP)
      dependent kinase (KT5720), Ca(2+)- and phospholipid-dependent kinase (Calphostin
      C), and cyclic guanosine 3':5'-monophosphate (cGMP)-dependent kinase (KT5823) and
      then treated with a corresponding kinase stimulator (dibutyryl cAMP, phorbol 12
      myristate 13-acetate and dibutyryl cGMP, respectively) to determine the effect on
      the acrosome reaction. Appropriate controls were performed. Zonae obtained from
      the unfertilized oocytes of women attending an IVF program were solubilized using
      acidic NaH2PO4, and the effect of solubilized ZP on the acrosome reaction was
      tested in dose-response fashion. Comparative studies with solubilized, zona-free
      oocyte-treated spermatozoa were performed. The effect of the kinase inhibitors on
      the solubilized ZP-induced acrosome reaction was then determined. RESULTS: No
      significant stimulation of the acrosome reaction by kinase stimulators occurred
      when spermatozoa were pretreated with inhibitors of the kinases, in contrast to
      the controls. Capacitated spermatozoa incubated with 2, 4, and 6 solubilized ZP
      showed a dose-dependent increase in the acrosome reaction. Solubilized oocytes
      had no effect on the acrosome reaction. Pretreatment of spermatozoa with kinase
      inhibitors significantly lowered the acrosome reaction induced by solubilized ZP
      but not completely. When a "cocktail" of the three inhibitors was used, a
      significant reduction in the acrosome reaction occurred in comparison with single
      inhibitor treatment. CONCLUSION: The present data indicate a role for human ZP
      induced activation of multiple second messenger pathways, involving kinases A, C,
      and G in the human sperm acrosome reaction.

PMID- 8137981
TI  - Localization of fibronectin on the surface of human spermatozoa and relation to
      the sperm-egg interaction.
AB  - OBJECTIVES: The mechanism of human sperm-oolemma adhesion and penetration as well
      as localization of fibronectin on the sperm head and its relation to
      fertilization were investigated. DESIGN: Sperm-oolemma interaction was examined
      with an in vitro assay of the human sperm-zona-free hamster egg interaction.
      Localization of fibronectin on the surface of human spermatozoa was observed by
      the back scattered electron imaging mode of the scanning electron microscopy
      (SEM). RESULTS: It was confirmed by observations under SEM that the anterior tip
      of the sperm head is the first to come into contact with the egg plasma membrane
      but that the equatorial segment of the sperm head is the first to be trapped by
      microvilli of the plasma membrane and that the postacrosomal region is first
      incorporated into ooplasm. Localization of fibronectin on the equatorial segment
      of the human sperm head was detected by SEM. Antifibronectin antibodies inhibited
      human sperm-oolemma adhesion significantly. CONCLUSIONS: Important involvement of
      fibronectin in the gamete interaction was made clear by the fact that fibronectin
      is localized in the region where a spermatozoon is fused first with the egg
      plasma membrane during fertilization and that the sperm adhering to the egg is
      inhibited by antifibronectin antibodies.

PMID- 8137982
TI  - Histopathological and adhesion formation after incision using ultrasonic
      vibrating scalpel and regular scalpel in the rat.
AB  - OBJECTIVE: To evaluate and to compare changes that occur in the uterine tissue of
      the rat after a standard incision with an ultrasonic vibrating scalpel and with a
      regular scalpel. SETTING: Sprague-Dawley white rats (Charles River Canada Inc.,
      St. Constant, Quebec, Canada) in a conventional laboratory setting.
      INTERVENTIONS: A standardized incision was performed on the uterine horn with a
      regular scalpel on one uterine horn and with an ultrasonic scalpel on the
      opposite horn. MAIN OUTCOME MEASURES: Degree of adhesions and histopathological
      changes of the uterine horns. RESULTS: The degree of adhesion formation was
      similar, but the uterine horn distal to the incision was dilated in most uterine
      horns that were incised with ultrasonic scalpel. The degree of coagulation
      necrosis was significantly higher 7 and 14 days after incision with an ultrasound
      scalpel than after incision with a regular scalpel. CONCLUSION: The use of an
      ultrasonic vibrating scalpel is associated with more tissue injury than that of a
      regular scalpel, but it does not produce more adhesion formation.

PMID- 8137983
TI  - Experience with transcervical fallopian tube catheterization.
AB  - Transcervical fallopian tube catheterization has been evaluated on a group of
      patent tubes in both a model of the human uterotubal complex and during
      hysterosalpingography. The technique appears to be unreliable and tubal
      catheterization occurs infrequently.

PMID- 8137984
TI  - Pregnancy after intrauterine insemination with sperm retrieved from the rectum.
AB  - A pregnancy, which was achieved with semen retrieved from the rectum of a male
      with urethrorectal fistula, is reported. The pregnancy was established after IUI
      with repeatedly washed sperm. Semen maintains its fertilization capacity even
      after exposure to the rectal environment.

PMID- 8137985
TI  - Successful pregnancies with unstimulated cycle oocyte donation using an
      antagonist of gonadotropin-releasing hormone.
AB  - We achieved two ongoing pregnancies in five older recipients with natural cycle
      oocyte donation from five young donors using a GnRH antagonist, with hMG and hCG
      to complete oocyte maturation. This provides a new alternative to ovarian
      stimulation for both oocyte donation and routine IVF.

PMID- 8137986
TI  - Aberrant estradiol flare despite gonadotropin-releasing hormone-agonist-induced
      suppression is associated with impaired implantation.
AB  - Our results confirm the previous report that rapid suppression by GnRH-a is
      favorable relative to delayed suppression (1). They further indicate that the
      pattern of E2 production during GnRH-a-induced ovarian suppression may be
      predictive of cycle outcome. We suggest that imperfect pituitary suppression of
      bioactive LH as indicated by an aberrant rise in E2 during GnRH-a down-regulation
      may compromise oocyte quality and ultimately impair implantation. Further study
      of follicular phase E2 response to GnRH-a suppression may provide a prognostic
      marker for implantation.

PMID- 8137987
TI  - Treatment of severe ovarian hyperstimulation syndrome by ultrafiltration and
      reinfusion of ascitic fluid.
AB  - Two severe OHSS patients were treated by ultrafiltration and reinfusion of their
      ascitic fluid. Improvement of symptoms was marked after this treatment with no
      complications, and termination of pregnancy was avoided. Treatment of OHSS with
      this ultrafiltration and reinfusion method may help to resolve serious cases of
      OHSS and become a useful treatment for severe OHSS.

PMID- 8137988
TI  - Short-term corticosteroid treatment does not improve implantation for embryos
      derived from subzonal insertion of sperm.
AB  - A total of 111 patients undergoing treatment for male factor infertility using
      SUZI participated in the trial for one treatment cycle only. They were allocated
      to have either corticosteroid treatment to induce immunosuppression or placebo.
      An elevated beta-hCG was found in 25% (9 of 36) of patients having an ET and
      receiving treatment. The corresponding figure for the control group was 33% (10
      of 30). On ultrasound examination, fetal hearts were found in 22% (8 of 36) and
      20% (6 of 30), respectively, of patients having an ET. chi 2 analysis showed no
      difference in the results. When the results were analyzed on a per oocyte basis
      there was no significant difference in the implantation rate.

PMID- 8137989
TI  - Effect of systemic hyperandrogenism on the adrenal response to
      adrenocorticotropin hormone.
AB  - A virilized patient with an androgen-producing ovarian tumor was used to
      illustrate the effect of chronic hyperandrogenism on the adrenal response to
      ACTH. The accumulation rates of substrates for 3 beta-ol dehydrogenase, 21
      hydroxylase, and 11 beta-hydroxylase remained unchanged after oophorectomy. This
      suggests that chronic hyperandrogenism does not affect the activity of enzymes
      involved in adrenal steroidogenesis.

PMID- 8137990
TI  - The hyperandrogenic-insulin-resistant acanthosis nigricans syndrome: therapeutic
      response.
AB  - The hyperandrogenic-insulin-resistant acanthosis nigricans syndrome affects
      between 2% and 5% of hirsute women and is characterized by INS resistance,
      elevated INS levels, acanthosis nigricans, and androgen excess. These patients'
      response to therapy is unclear, although long-acting GnRH-a suppression has been
      proposed. The objective of this study was to determine the success of OC in
      suppressing the hyperandrogenemia of five patients with the hyperandrogenic
      insulin-resistant acanthosis nigricans syndrome and the subsequent response to
      GnRH-a suppression of those women failing initial therapy. After 6 months of OC
      and SPA therapy, four patients experienced adequate suppression of free T, an
      increase in SHBG levels, and a subjective improvement in hair growth rate. Two
      also reported an improvement in hair texture. The total and free T levels in the
      fifth patient did not suppress after 8 months of OC therapy. Nevertheless, in
      this patient the administration of a GnRH-a along with hormonal replacement and
      SPA adequately suppressed free and total T, increased SHBG, and dramatically
      decreased the shaving interval. In conclusion, although GnRH-a suppression and
      hormonal replacement can be helpful in patients not responding to standard
      therapy, the majority of patients with the hyperandrogenic-insulin-resistant
      acanthosis nigricans syndrome will respond favorably to OC treatment. It is also
      clear that although hyperinsulinemia augments LH-stimulated androgen biosynthesis
      in vivo, it does not appear to be able to initiate or maintain androgen
      production in the absence of adequate gonadotropin stimulation.

PMID- 8137991
TI  - Contrasting effects of a gonadotropin-releasing hormone agonist and antagonist on
      the secretion of free alpha subunit.
AB  - Gonadotropin-releasing hormone agonists and antagonists have initial divergent
      effects on the pituitary secretion of intact biologically active gonadotropins
      and long-term divergent effects on the secretion of free alpha-subunit. The
      antagonists appear to function as true competitive inhibitors, blocking the
      stimulatory effects of endogenous GnRH without evoking any known postreceptor
      activity. The agonists, in contrast, initially stimulate pituitary secretion and
      then incompletely desensitize the gonadotrope, resulting in suppression of intact
      gonadotropin, but not free alpha-subunit, secretion. The mechanisms by which GnRH
      a produce this incomplete gonadotrope desensitization and facilitate limited
      postreceptor activity remain to be elucidated.

PMID- 8137992
TI  - Communication of the intracranial space with sphenoid bone marrow in mice.
AB  - Tritiated thymidine and Ehrlich ascites tumour cells were injected intrathecally
      in adult Balb/c mice. Thymidine penetrated easily into the sphenoid bone marrow,
      where it labelled numerous leukocytes. The microvessel wall constituted a partly
      penetrable barrier against the infiltration of Ehrlich ascites tumour cells from
      arachnoid space into the bone marrow. A possible physiological role of the
      drainage of substances from the brain into the bone marrow is discussed.

PMID- 8137993
TI  - Usability of the hypoosmotic swelling "Water-test"--a simple method to assess
      sperm membrane integrity in mouse spermatozoa.
AB  - The functional integrity of the membrane of sperm from 3 strains of mice (BALB/c,
      CBA/KW, and C57BL/KW) was assessed by studying the swelling reaction of the sperm
      when suspended in a medium of distilled water. The results were correlated with
      analysis of sperm motility and those of Eosin-Y staining. The results obtained
      from the Eosin-Y test and "Water-test" differed (P < 0.01) between strains
      C57BL/KW and both BALB/C, and CBA/KW. A good correlation was observed in all
      strains of mice between the values of the "Water-test" and those for Eosin-Y
      staining (P < 0.01).

PMID- 8137994
TI  - Brown adipose tissue proteins impede thymus development in rats.
AB  - The biological effect of the protein component of hypertrophic brown dispose
      tissue (BAT) of ground squirrels on thymus development in immature Wistar rats
      was studied morphologically. It was established that repeated intraperitoneal
      injections of BAT proteins produced remarkable regression and hypotrophy in the
      thymus parenchyma. This was demonstrated anatomically and histologically by a
      decrease in the weight of the thymus treated rats as well as as in the size of
      the cortical areas of lobules and an expansion of their medulla; also by the
      thinning away or disappearance of the superficial cortex, a decrease in the
      number of blasts and immature forms of lymphocytes in mitosis, but an
      intensification of phagocytosis.

PMID- 8137995
TI  - Gap junction density in human myometrium at term revealed by an anti-peptide
      antibody and laser scanning confocal microscopy.
AB  - The concept that the progesterone-estrogen ratio determines gap junction
      abundance in myometrium has developed from studies in laboratory animals. In the
      humans, however, gap junctions form in abundance at term despite a high
      progesterone-estrogen ratio. We have therefore examined the relationship between
      contractile activity, progesterone and estrogen levels and gap junction abundance
      in human myometrium at term. Myometrial tissue obtained from women who had an
      elective or emergency Cesarean operation at the 38th or 39th week of pregnancy
      was immunohistochemically examined using a polyclonal antiserum raised against a
      synthetic peptide matching part of the sequence of connexin43, the principal
      component of myometrial gap junctions. The concentration of progesterone and
      estradiol in the maternal blood was measured by means of radio-immunoassay. The
      number of gap junctions was estimated by counting of punctate staining patterns
      obtained in myometrial tissue as viewed by laser confocal microscopy and
      calculated per 1 microns 3 of tissue. The number of gap junctions measured was
      found to be related to the presence or absence of labor. In the myometrium of
      women in labor (active phase), the number of gap junctions was highest (45.25 +/-
      35). When the myometrium was not contracting (non-labor) and when contractions
      were weak (pre-labor) the number of gap junctions was low (15.16 +/- 10-5.75 +/-
      5). In the pre-and active phase of labor, the concentration of progesterone in
      maternal blood was significantly higher (P < 0.025 and 0.03, respectively) than
      in women who were not in labor. The present study shows the potential of using
      optical section series obtained by laser confocal microscopy for the
      quantification and mapping of the three-dimensional distribution of gap junctions
      in human myometrium at term.

PMID- 8137996
TI  - Successful mafosfamide purging of bone marrow from chronic myelogenous leukemia
      (CML) cells.
AB  - The in vitro sensitivity of human chronic myeloid leukemia-blast crisis and
      chronic phase (CML-BC and CML-CP, respectively) cells as well as adherent cell
      depleted, T lymphocyte-depleted normal bone marrow cells (A-T-NBMC) to various
      concentrations of mafosfamide (ASTA Z7654), was examined by colony formation
      assay in the presence of IL-3 and GM-CSF, to test the possibility of purging of
      BMC from CML cells. Colony formation by CML cells was inhibited more efficiently
      than by NBMC. After the incubation with 50 micrograms/ml or 100 micrograms/ml of
      mafosfamide, the growth of leukemic CFU-GM was totally abrogated in 2/11 or 9/11
      cases of CML-BC and in 1/7 or 6/7 cases of CML-CP, respectively. At the same time
      the CFU-GM arising from normal BMC were not inhibited totally with 50 or 100
      micrograms/ml of the drug in any of five experiments. CML cells were still unable
      to form secondary colonies, while normal BMC were capable of regrowth. The CD34+
      cells isolated form CML-BC and CML-CP patients were also more susceptible to
      mafosfamide cytotoxicity in comparison to CD34+ cells derived from NBMC. To
      confirm the possibility of purging, CML-BC cells were mixed with NBMC (1:1) and
      incubated with mafosfamide. Finally, the growing colonies were examined for the
      presence of bcr/abl hybrid gene by reverse transcriptase-Taq polymerase chain
      reaction (RT-PCR) and specific hybridization. The bcr/abl gene was not detected
      in the colonies growing after 100 micrograms/ml, and the signal was diminished
      after incubation with 50 micrograms/ml of mafosfamide, as compared to control.
      These results strongly suggest that high concentrations of mafosfamide may be
      useful for the purging of autologous BMC from CML cells.

PMID- 8137997
TI  - Studies on effects of culture conditions and age of donor on hippocampal neurons
      in vitro.
AB  - The hippocampus is a brain structure of pivotal role in many physiological and
      pathological responses including memory formation, epilepsy and ischemia.
      Understanding of these processes requires a good knowledge of hippocampal
      neurons. In vitro culture offers a tool to study these cells in a controlled
      environment. In order to optimize culture conditions several growth parameters
      were investigated in hippocampal neuronal cultures derived from rats of different
      age: 18-day old fetuses, newborns and 5-day old rat pups, maintained in either
      serum-containing or chemically defined media. Usefulness of particular culture
      conditions for special purposes is discussed.

PMID- 8137998
TI  - Changes in the distribution of immunoglobulin G cellular uptake in the injured
      cerebral hemisphere in mice.
AB  - In the injured mouse cerebral hemisphere changes in the number and distribution
      of immunoglobulin G (IgG)-containing cells were examined. First IgG
      immunopositive cells appeared close to the edge of lesion 10 min. following the
      injury. The total number of IgG-containing cells and the size of area occupied by
      them were maximal on the 1st posttraumatic day and then gradually decreased.
      However, 30 days after injury few IgG-immunopositive cell were still visible
      close to the injury site.

PMID- 8137999
TI  - Localization of glucose-6-phosphatase activity in the rat cardiac muscle by
      cobalt-based cytochemistry.
AB  - The histocytochemical method for the detection of glucose-6-phosphatase activity
      has been studied in the rat heart tissue by using cobalt-capture technique. The
      incubation medium had the following ingredients: cobalt chloride, PIPES-NaOH
      buffer pH = 6.7, glucose-6-phosphate disodium salt and phenylalanine. Cobalt was
      revealed by using a solution of 1% ammonium sulfide and was fixed by osmium
      tetroxide. The most effective concentration of cobalt chloride was 50 mM. With a
      concentration lower than 30 mM, the reaction products were not determined. With a
      higher concentration, a small non-specific precipitation was visualized.
      Ultracytochemically, a strong enzyme reaction was present in the nuclear
      envelopes of cardiac myocytes, endotheliocytes and in the sarcoplasmic reticulum.
      These results imply that the method used is valid and can be recommended for
      studying the localization of glucose-6-phosphatase activity.

PMID- 8138000
TI  - Ultrastructural observations of nuclear bodies in the epithelial cells of human
      conjunctiva.
AB  - Nuclear bodies (NBs) are intranuclear structures described in normal and
      pathologically altered cells of humans and animals. The NBs are 0.3-1.5 microns
      round structures. Their function is unknown. In the present paper, we describe
      NBs in the nuclei of the conjunctiva epithelial cells in one patient with
      cicatricial pemphigoid (CP) and in an another one without conjunctival pathology.
      We observed increase in the frequency of the NBs of type I occurring in the
      conjunctival cells in CP patient as compared to the healthy control. This is the
      first report to describe nuclear bodies in the human conjunctiva.

PMID- 8138001
TI  - Mast cells in elastic cartilage of the human epiglottis.
AB  - Light and transmission electron microscopy revealed in the elastic cartilage of
      the human epiglottis the presence of mast cells. Cytoplasmic granules of these
      cells contain characteristic cylindrical bodies, whose texture is different from
      that found in cytoplasmic granules of mast cells from other sites. The presence
      of mast cells in elastic cartilage, described for the first time, and the
      different substructure of their cytoplasmic granules, is considered as another
      proof of the heterogeneity of that cell type.

PMID- 8138002
TI  - A correlative study of bronchial cytology, bronchoalveolar lavage (BAL) and serum
      tumor markers in the diagnosis of lung carcinoma.
AB  - In order to evaluate the diagnostic value of lavage CEA and SCC-Ag in combination
      with other parameters such as serum CEA and SCC-Ag, sputum and bronchial brushing
      cytology, we studied 30 patients with lung carcinoma and 12 with nonmalignant
      lung disease. All four tests combined, resulted in an increase in the predictive
      accuracy for diagnostic lung carcinoma to 87 per cent, a value which is much
      above the approximately 50 per cent level achieved by each test alone. Hence
      lavage CEA and SCC-Ag appears to be a useful accessory test in the diagnosis of
      lung carcinoma, particularly when combined with other diagnostic procedures
      currently in use.

PMID- 8138003
TI  - Age-related changes in glycosaminoglycans of human intervertebral discs.
AB  - The age-related changes in glycosaminoglycan composition of human intervertebral
      discs were studied. Large number of tissue samples taken from 301 individuals at
      autopsy or at operation of prolapsed discs was investigated. It was found that
      the ageing process is accompanied by a progressive decrease in GAG content, both
      in annulus fibrosus and in nucleus pulposus. The GAG: collagen ratio
      significantly decreases. The KS and Ch-6-S were found to be the most abundant
      GAGs in both parts of the disc and their amounts decrease during the ageing. A
      distinct, age-related increase in KS:Ch-S and Ch-6-S:Ch-4-S ratios was observed.
      Significant quantitative differences between the GAG contents in normal and
      prolapsed discs were found. The nuclei pulposi of prolapsed discs contained less
      GAGs, especially KS and Ch-6-S in comparison to normal tissue of the same age.
      Furthermore, the age-related decline of GAGs:collagen ratio was more distinct in
      the prolapsed discs. It seems that these differences in GAG composition may be
      important in the mechanism of predisposition to discs prolapse.

PMID- 8138004
TI  - Studies on oestrone sulphate sulphohydrolase from human placenta nuclear
      envelopes--solubilization and properties.
AB  - Kinetic properties of human placenta nuclear envelope oestrone sulphate
      sulphohydrolase were determined in envelope suspension, Triton X-100 solubilized
      enzyme preparations and in partially purified enzyme preparations. Purification
      of the enzyme(s) extracted with Triton X-100 was performed by three alternative
      procedures: Bio-gel A 15 m chromatography, DEAE-cellulose chromatography and Con
      A-Sepharose chromatography. The nuclear envelope suspension revealed optimal
      hydrolysis of oestrone sulphate at pH 8.2; the Triton X-100 solubilized enzyme
      exhibited optimal activities at pH 6.6 and 8.6. Three distinct activity peaks of
      oestrone sulphate hydrolysis were found for the partially purified enzyme
      preparations: at pH 6.2 (5.8-6.6), at pH 7.0 and pH 8.4 (8.0-8.8). The influence
      of the oestrone sulphate concentration on the enzyme activity determined at pH
      6.2 exhibited a sigmoid saturation kinetics with all enzyme preparations except
      that obtained after Con-A Sepharose chromatography. The value of Hill (h)
      coefficient was 2; S0.5 = 65 microM, the K'm = 4.9 x 10(-9) M. At pH 7.0 and 8.4,
      the influence of oestrone sulphate concentration on enzyme activity revealed a
      Michaelis-Menten saturation kinetics; the respective values of Km were 4.2 +/-
      1.1 x 10(-6) M and 1.08 +/- 0.11 x 10(-4) M. The Km value of oestrone sulphate
      hydrolysis of the enzyme preparation after Con-A Sepharose chromatography
      determined at pH 6.2, 7.0 or 8.1 was 4.0 x 10(-4) M.

PMID- 8138005
TI  - Accessory nuclei in the oocytes of the cockoo wasp, Chrysis ignita (Hymenoptera:
      Aculeata).
AB  - In the oocytes of Chrysis ignita, accessory nuclei (AN) arise before yolk
      formation, during advanced previtellogenesis. Two categories of AN, small (SAN)
      and large (LAN) can be distinguished at this stage of development. Both AN
      categories contain two dense, morphologically distinct inclusions (termed A and
      B) immersed in a translucent matrix. AN are exclusively located in the cortical
      (peripheral) ooplasm. Moreover, LAN are asymmetrically distributed also along the
      antero-posterior axis of the oocyte, and occur preferentially in the anterior
      pole periplasm. In contrast, the distribution of SAN is uniform throughout the
      periplasm.

PMID- 8138006
TI  - Autoradiographic studies on 3H-fucose incorporation into manubria and its
      translocation to antheridial space during spermatogenesis in Chara vulgaris L.
AB  - The internal space of antheridium in Chara vulgaris L. is filled with the PAS
      positive polysaccharide mucilage. It is produced and secreted by non-generative,
      polyploidal cells--manubria. Autoradiographic studies with the use of 3H-fucose
      have shown that this precursor is incorporated into polysaccharidial compounds at
      the manubrium surface. The dynamics of this process is different in proliferative
      phase than after symplasmic isolation of antheridium. The translocation of
      mucilage into antheridial space is very intensive, especially at the older
      developmental stages of antheridium. The data obtained after 12-hour
      postincubation indicated secondary metabolic changes of mucilage. The decrease in
      total radioactivity per investigated section is most intensive by the end of
      spermatogenesis. These facts seem to confirm the assumption about nutritive role
      of mucilage filling Chara antheridium during the process of spermatogenesis.

PMID- 8138007
TI  - Two cytosolic protein families implicated in lipid-binding: main structural and
      functional features.
AB  - 1. According to the important biological role of fatty acids and phospholipids in
      cell membranes, two cytosolic proteins implicated in their binding and transport
      in brain were considered, namely: Fatty Acid-Binding Protein and basic 21 kDa
      protein. 2. They were reviewed as well as their related protein families. 3.
      Although the two protein groups do not present significant sequence homologies,
      they share several similar properties and might thus be implicated in common
      physiological functions.

PMID- 8138008
TI  - The effects of fatty acids on lymphocyte functions.

PMID- 8138009
TI  - Role of glutamate dehydrogenase reaction in the control of citrate pool in yeast.
AB  - 1. Role of NADP-glutamate dehydrogenase in the depletion of citrate was analyzed
      using permeabilized yeast cells. 2. Citrate was converted to 2-oxoglutarate,
      which was then metabolized to glutamate by NADP-glutamate dehydrogenase in the
      presence of ammonium ion. 3. Formation of 2-oxoglutarate plus glutamate was in
      good agreement with the concentration of citrate decreased. Glutamate formation
      can be a good indicator of the depletion of citrate, because 70% of the citrate
      decreased was converted to glutamate. 4. Glycolytic activity was closely
      correlated with the decrease in citrate under the in situ conditions. 5. NADP
      glutamate dehydrogenase increased in anaerobically grown yeast cells. 6. An
      effective depletion of citrate by increased synthesis of NADP-glutamate
      dehydrogenase can explain the lowered mechanism of citrate causing glycolytic
      stimulation under the anaerobic growth conditions of yeast.

PMID- 8138010
TI  - In vitro Ca deposition by rat matrix vesicles: is the membrane association of
      alkaline phosphatase essential for matrix vesicle-mediated calcium deposition?
AB  - 1. Phosphatidylinositol phospholipase C (PI-PLC) treatment of rachitic rat matrix
      vesicles (MVs) released about 80% of membrane-bound alkaline phosphatase (ALP),
      AMPase, PPiase into the media. 2. About 20% hydrolytic activity was not released
      from MV membranes by PI-PLC treatment. 3. SDS-polyacrylamide gel electrophoresis
      and Western blot analysis showed only one immunoreactive protein corresponding to
      the molecular weight of ALP present in the soluble fraction after PI-PLC
      treatment. 4. The specific activity of the released ALP was at least 5-fold
      higher than the residual activity. 5. After PI-PLC treatment, MVs also
      demonstrated an 80% reduction of AMP- or beta GP-dependent calcium deposition. 6.
      The soluble fraction containing 80% of ALP activity was unable to support calcium
      deposition. The mixing of the soluble and insoluble fractions after PI-PLC
      treatment failed to fully restore calcium-depositing activity.

PMID- 8138011
TI  - The major dog pancreas protein recognized by an antiserum to dog prostate
      kallikrein is the anionic trypsin.
AB  - 1. On the basis of its immunoreactivity with a polyclonal antiserum to dog
      prostate kallikrein in Western blot experiments, a 30 kDa protein was purified
      from the pancreas of the dog using ion-exchange and gel filtration
      chromatography. 2. That protein was identified as the anionic trypsin by its NH2
      terminal amino acid sequence. 3. The immunoreaction occurred despite an overall
      amino acid homology which was limited to 39% between the prostate kallikrein and
      anionic trypsin. 4. Otherwise, the anti-prostatic kallikrein antiserum was rather
      specific since it did not react with dog cationic trypsin, dog renal kallikrein
      and human prostate specific antigen.

PMID- 8138012
TI  - The role of glutamine and glucose analogues in metabolic inhibition of human
      myeloid leukaemia in vitro.
AB  - 1. Glutamine analogues L-[alpha S,5S]-alpha-amino-3-chloro-4,5-dihydro-5
      isoxazoleacetic acid (acivicin) and 6-diazo-5-oxo-L-norleucine (DON) have been
      shown to possess cytotoxic activity against a wide variety of animal and human
      xenografted solid tumours, however their potential in man has been limited by
      toxicity. 2. We have analysed the effects of acivicin and DON on glutamine
      utilization to determine whether the reason for the disappointing therapeutic
      profile is solely due to the inefficient inhibition of glutamine metabolism. 3.
      Human myeloid leukaemic cells treated with acivicin inhibited ribonucleotide
      biosynthesis but not energy production via glutaminolysis and had little effect
      on viability, whereas treatment with DON inhibited both ribonucleotide
      biosynthesis and glutamine oxidation and resulted in reduced viability. 4.
      Treatment of the myeloid leukaemic cells with the glucose analogue 2-deoxy-D
      glucose in addition to DON potentiated the inhibition of de novo nucleotide
      biosynthesis, glutaminolysis and glycolysis, and caused a further reduction in
      cell viability. 5. These results provide further support for the essential role
      of glutamine in cellular metabolism, and indicate that use of the glutamine
      analogue DON in the treatment of acute myeloid leukaemia may be more clinically
      effective if used in combination with 2-deoxy-D-glucose.

PMID- 8138013
TI  - Mitochondrial and peroxisomal fractions derived from human white adipocytes.
AB  - 1. A procedure is described for the separation of intact peroxisomes from human
      white adipocytes using a linear metrizamide gradient (20-50% w/v). 2. Peroxisomes
      were found in the high density region of the gradient in an intact form. 3.
      Mitochondria were distributed in the high density and low density regions of the
      gradient. 4. Lysosomes separated well from the peroxisomes, occurring only in the
      low density region of the gradient. 5. Low levels of glyoxylate cycle enzyme
      activities (isocitrate lyase and malate synthase) were detected within the light
      and heavy mitochondrial pellet fractions.

PMID- 8138014
TI  - Effect of depletion of glutathione by buthionine sulfoximine on lipid
      peroxidation in rats acutely treated with ethanol.
AB  - 1. The effect of depletion of glutathione (GSH) by DL-buthionine-S,R-sulfoximine
      (BSO) on lipid peroxidation in rats acutely treated with ethanol was
      investigated. 2. BSO pretreatment has not been found to potentiate an increase in
      liver, brain and erythrocyte lipid peroxide levels.

PMID- 8138015
TI  - Identification of a microsomal retinoic acid synthase as a microsomal cytochrome
      P-450-linked monooxygenase system.
AB  - 1. To characterize an enzyme which metabolizes retinal in liver microsomes,
      several properties of the enzymatic reaction from retinal to retinoic acid were
      investigated using rabbit liver microsomes. 2. The maximum pH of the reaction in
      the liver microsomes was 7.6. 3. The Km and Vmax values for all-trans, 9-cis and
      13-cis-retinals were determined. 4. The reaction proceeded in the presence of
      NADPH and molecular oxygen. 5. The incorporation of one atom of molecular oxygen
      into retinal was confirmed by using oxygen-18, showing that the reaction
      comprised monooxygenation, not dehydrogenation. 6. The monooxygenase activity was
      inhibited by carbon monoxide, phenylisocyanide and anti-NADPH-cytochrome P-450
      reductase IgG, but not by anti-cytochrome b5 IgG. 7. The enzymatic activity
      inhibited by carbon monoxide was photoreversibly restored by light of a
      wavelength of around 450 nm. 8. The retinal-induced spectra of liver microsomes
      with three isomeric retinals were type I spectra. 9. The microsomal monooxygenase
      activity induced by phenobarbital or ethanol were more effective than that by 3
      methylcholanthrene, clotrimazole or beta-naphthoflavone. 10. These results showed
      that the monooxygenase reaction from retinal to retinoic acid in liver microsomes
      is catalyzed by a cytochrome P-450-linked monooxygenase system.

PMID- 8138016
TI  - Effect of bovine milk antigens and egg lysozyme on the binding of 59Fe
      lactoferrin to platelet plasma membranes.
AB  - 1. Platelets bind specifically to lactoferrin. A significant similarity between
      human lactoferrin and some bovine milk proteins has been established. 2. Because
      of the structural homology of lactoferrin and cows milk proteins they are able to
      influence lactoferrins regulatory function on the level of its binding to
      membrane receptors on platelets. 3. An inhibitory effect of bovine alpha
      lactalbumin and of beta-lactoglobulin on lactoferrin-receptor interaction was
      shown. 4. Bovine alpha-lactalbumin competes with lactoferrin for the binding
      sites. 5. Scatchard plot analysis of data shows one binding site for lactoferrin
      in the presence of alpha-lactalbumin with an affinity constant, Ka = 0.46 x 10(9)
      mol/l and 335 receptors/cell. 6. The inhibitory effect of beta-lactoglobulin
      reaches 62% and is different for the common fraction beta-lactoglobulin and the
      genetic variants beta-lactoglobulin A and B. 7. beta-lactoglobulin does not
      compete with lactoferrin for the membrane receptors. 8. Bovine casein and egg
      lysozyme stimulate 59Fe-lactoferrin binding to the receptors. The mechanism of
      these effects is still unknown. 9. Tested alimentary antigens are able to
      interact with lactoferrin and also with some platelet membrane structures. 10.
      Established changes in lactoferrin binding to the platelet membrane might be in
      relation to lactoferrins regulatory function and (or) eliminating mechanisms of
      these alimentary antigens.

PMID- 8138017
TI  - Lipid peroxidation affects catalytic properties of rat liver mitochondrial
      monoamine oxidases and their sensitivity to proteolysis.
AB  - 1. Lipid peroxidation (LPO) in rat liver mitochondria decreased the activity of
      monoamine oxidase (MAO) with physiological substrates serotonin and 2
      phenylethylamine (by 15-30%) and induced deamination of glucosamine, which was
      highly sensitive to selective MAO A inhibitor pirlindole. 2. The LPO-induced
      changes in catalytic properties of MAOs are accompanied by their increased
      susceptibility to trypsinolysis, however sensitivity to inhibition by imipramine,
      chlorpromazine and spermine are insignificantly changed. 3. It is suggested that
      these results reflect LPO-induced conformational changes of enzyme molecules in
      membrane rather than their membrane topography.

PMID- 8138018
TI  - A comparative study on lipid peroxidation in cerebral cortex of stroke-prone
      spontaneously hypertensive and normotensive rats.
AB  - 1. Lipid peroxidation and membrane-related enzyme changes in the cerebral cortex
      of stroke-prone rats (SHRSP) and normotensive rats were examined at 5 and 20
      weeks of age. 2. In vivo formation of thiobarbituric acid-reactant substances was
      higher in SHRSP at 20 weeks of age and in vitro generation of free
      malondialdehyde was greater in SHRSP brains, both at 5 and 20 weeks of age, as
      compared with those in WKY. 3. Membrane-associated enzymes such as Na/K-ATPase
      and 5'-nucleotidase activities were lower in 20-week-old SHRSP than in age
      matched WKY. 4. These results indicate how very prone the SHRSP brain is toward
      lipid peroxidation and subsequent membrane-related enzyme changes.

PMID- 8138019
TI  - Calcium transport and calcium activated ATPase activity in microsomal vesicles of
      rat gastric mucosa.
AB  - 1. Microsomal and plasma membrane vesicles, isolated from rat gastric mucosa,
      were found to exhibit Ca(2+)-dependent ATPase activities of 14.1 +/- 1.4 and 7.8
      +/- 1.1 mumol/mg/hr, respectively. The optimum conditions for the microsomal
      Ca(2+)-ATPase was pH 6-7, and required Mg2+, while divalent cation such as Cu2+,
      Zn2+, Fe2+, Ba2+ and Cd2+ had no significant effect. 2. As in the case of Ca2+,
      Mg(2+)-ATPase, the Ca2+ uptake activity of the microsomal membrane required Mg2+.
      Both processes were stimulated by submicro molar concentrations of Ca2+ and the
      apparent Km for Ca2+, Mg2+ ATPase and Ca2+ uptake activities were 0.06 microM and
      0.02 microM, respectively. 3. Divalent cations Ba2+ and Fe2+, inhibited both
      microsomal activities, while Zn2+ and Cd2+ showed no effect on them. However, the
      monovalent cation K+ did not stimulate Ca2+, Mg(2+)-ATPase and Ca2+ uptake
      activities. 4. The Ca2+ pumping ATPase of rat gastric mucosal microsome cross
      reacted with a monoclonal antibody (mAb-5F10) against the human erythrocyte Ca2+
      pump. The apparent molecular weight of mucosal Ca2+ pump was 98 kDa. 5. Close
      relationship between the kinetic parameters of Ca2+, Mg(2+)-ATPase and Ca2+
      uptake activities, and the cross reaction of 98 kDa protein of mucosal microsome
      with erythrocyte Ca2+ pump antibody, strongly suggest the expression of Ca2+ pump
      in rat gastric mucosa.

PMID- 8138020
TI  - Isolation and characterization of fibrinogenase from Candida albicans NH-1.
AB  - 1. Fibrinogenase was isolated from Candida albicans NH-1 by DEAE-Cellulose,
      Sephadex G-75 and Sephadex G-100 column chromatographies. 2. The purified
      fibrinogenase gave a single band on disc polyacrylamide gel electrophoresis,
      isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. 3. The enzyme preparation had a molecular weight of 13,000,
      isoelectric point of pH 4.2 and possessed 117 amino acid residues. 4. The
      purified fibrinogenase possessed capillary permeability-increasing activity. 5.
      The enzyme hydrolyzed fibrinogen, casein, hide powder azure, azocoll hydrolytic
      activities and also hydrolyzed the oxidized B chain of insulin. The cleavage
      sites in the oxidized B chain of insulin were identified as Asp(3)-Glu(4),
      Glu(13)-Ala(14), Ala(14)-Leu(15), Tyr(16)-Leu(17), Arg(22)-Gly(23), Phe(25)
      Tyr(26) and Tyr(26)-Thr(27). 6. Fibrinogenase activity of this preparation was
      inhibited by alpha 2-macroglobulin antithrombin-III, o-phenanthroline, disodium
      ethylenediaminetetra acetic acid and dithiothreitol.

PMID- 8138021
TI  - Bovine aorta contains at least two related forms of heparan sulphate
      proteoglycan.
AB  - 1. The proteoglycan peak from anion exchange chromatography of an extract of
      bovine aorta was digested with chondroitinase ABC. The residual heparan sulphate
      proteoglycans were further purified by chromatography on Sepharose CL4B and DEAE
      Sephacel to yield two species, of high and low charge density. 2. Higher
      molecular weight material had a higher proportion of high charge density
      proteoglycan, while the lower molecular weight species had a higher proportion of
      low charge density heparan sulphate proteoglycan. 3. The two species shared
      epitopes as they both reacted with an antibody to heparan sulphate proteoglycan
      from bovine glomerular basement membrane. 4. On electron microscopy, both high
      and low charge density proteoglycans were visualized as 'tadpole-like' molecules,
      which showed a tendency to aggregate via their globular heads. 5. Bovine aortic
      smooth muscle cells were cultured in the presence of [35S]sulphate and
      [3H]glucosamine. Proteoglycans were isolated from medium and cell layer extract
      by the methods outlined above. 6. The major HSPG species isolated from medium
      were significantly larger than those from cell layer and displayed substantial
      heterogeneity in both size of HS chain after papain digestion and size of protein
      core after heparitinase digestion. 7. The major cell layer species yielded two HS
      species of widely differing mol. wt after papain digestion, and a very small
      protein core after heparitinase digestion. Therefore cell layer-associated HSPGs
      show a good deal more homogeneity than those found in the medium. 8. Further ion
      exchange chromatography after digestion with chondroitinase ABC revealed HSPG
      species of lower charge density, possibly derived from a hybrid chondroitin
      sulphate-dermatan sulphate proteoglycan (CS/DSPG) after removal of the CS/DS
      chains.

PMID- 8138022
TI  - Connectin content in rabbit cardiac and skeletal muscle.
AB  - 1. The contents of connectin in rabbit cardiac and skeletal muscle were estimated
      by densitometry of the bands in SDS gel electrophoresis. 2. The weight ratio of
      connectin to myosin was 1:9.5 in cardiac muscle and 1:4.2 in skeletal muscle. 3.
      Assuming that the molecular weights of myosin and skeletal muscle connectin were
      5.25 x 10(5) and 4.2 x 10(6) respectively, and a myosin filament consists of 300
      myosin molecules, it was calculated that there were approx. 4 connectin molecules
      per half of myosin filament in rabbit skeletal muscle. 4. In cardiac muscle, the
      molecular weight of connectin was assumed to be 3.6 x 10(6) and it was estimated
      that there were about 2 connectin filaments per half of myosin filament.

PMID- 8138023
TI  - Ascorbic acid inhibits protein tyrosine phosphatases in NIH 3T3 cells expressing
      human epidermal growth factor receptors.
AB  - 1. Physiological concentrations of ascorbic acid inhibited PTPase activity in HER
      14 cells. 2. Higher concentrations of ascorbic acid produced a weaker inhibitory
      effect on PTPase activity in HER 14 cells. 3. EGF prevented the inhibitory effect
      of ascorbic acid on PTPase activity in HER 14 cells. 4. The inhibitory effect of
      physiological concentrations of ascorbic acid on PTPase activity depends on
      density of the cell culture, with less dense populations exhibiting greater
      inhibition of PTPase activity. 5. These observations suggest that ascorbic acid
      might have a modulatory role in cellular phosphorylation-dephosphorylation
      events.

PMID- 8138024
TI  - Comparative structural analysis of human and rat 65 kDa tumor-associated
      phosphoproteins.
AB  - 1. A 65 kDa-tumor-associated protein (p65) was isolated from human and rat
      carcinoma cell culture media. Antibodies raised to the rat protein recognized an
      antigenically related protein in human cancer cell line. 2. Amino acid
      composition, N-terminal and internal sequence as well as peptide map and western
      blot analysis of the p65 strongly suggest a high degree of homology between the
      human and rat p65 proteins. 3. Homology searches indicated that p65 was not
      homologous to previously sequenced proteins, but that it may be related to
      proteins of the steroid receptor superfamily of genes, especially c-erb A gene.

PMID- 8138025
TI  - Differential effect of xanthopterin and biopterin on cell growth.
AB  - 1. Xanthopterin inhibited proliferation of primary renal proximal tubule cells
      (RPTC) and LLC-PK1 cells while in a growth phase but when incubated at confluence
      the cells were relatively insensitive. 2. The growth of malignant human prostate
      PC-3 cells was also inhibited by xanthopterin in a concentration and time
      dependent manner. 3. Dunning R3327 AT-3 rat prostate tumor cells which were
      exposed to xanthopterin in vitro before their in vivo inoculation resulted in
      smaller tumours while in vivo administration of xanthopterin following
      implantation also resulted in smaller tumors. 4. Xanthopterin exerts differential
      effects on cell growth dependent upon the cell origin and their state of
      proliferation.

PMID- 8138026
TI  - Metabolic and contractile differentiation of rabbit muscles during growth.
AB  - 1. A study was carried out of post-natal evolution of the oxidative, glycolytic
      and contractile capacities in various types of rabbit muscle. 2. At birth,
      muscles are non-differentiated and present very limited metabolic and contractile
      activity, metabolism is mainly oxidative in all muscles. 3. Although muscular
      discrimination is manifest from the sixth week after birth, the glycolytic
      metabolism reaches its maximum capacity only after six to eight weeks. 4.
      Subsequently, oxidative metabolic capacity steadily decreases until adulthood.

PMID- 8138027
TI  - Distribution of mammalian facilitative glucose transporter messenger RNA in
      bovine tissues.
AB  - 1. The complementary DNA for five human facilitative glucose transporters (GLUT1,
      GLUT2, GLUT3, GLUT4 and GLUT5) were used to determine the distribution of
      facilitative glucose transporter mRNA in bovine tissues by Northern blotting.
      Under high stringency hybridization conditions, a single 2.8 kb transcript of
      GLUT1 was seen in all bovine tissues examined except liver. Mammary gland had the
      highest abundance of GLUT1 mRNA. 2. Four GLUT2 transcripts of 6.3, 3.8, 2.2 and
      1.6 kb were observed to be most abundant in liver, with lower abundance in kidney
      and duodenum. 3. Only a very low level of GLUT3 mRNA was detected in the mammary
      gland, skeletal muscle and duodenum. 4. Skeletal muscle contained the greatest
      abundance of GLUT4 mRNA, which was barely detectable in omental fat, kidney and
      mammary gland. 5. Transcripts of GLUT5 mRNA were detected in relatively high
      abundance in liver and kidney, and in lower abundance in the duodenum and mammary
      gland. 6. With the exception of the mammary gland, for which human data have not
      been reported, the distributions of GLUT1, 2 and 4 mRNA for the bovine tissues
      examined are similar to that reported for humans. On the other hand, the
      distributions of GLUT3 and 5 mRNA in the bovine differ from those reported for
      humans.

PMID- 8138028
TI  - Energy metabolism of human erythrocytes in psoriasis.
AB  - 1. Adenine nucleotide concentrations and metabolism in red blood cells (RBC) and
      RBC ghosts from psoriatic patients and healthy subjects were compared. 2. The ATP
      and total adenine nucleotide levels and the adenylate energy charge (EC) were
      elevated in the blood from psoriatic patients. 3. The rate of glycolytic
      production of ATP by intact RBC was unchanged, but the Na+, K(+)-ATPase activity
      of RBC ghosts was decreased significantly in psoriasis. 4. Results suggest that
      the defect in adenine nucleotide metabolism is a systemic manifestation of
      psoriasis, and that the quantification of adenine nucleotides in RBC and in whole
      blood samples may be of pathophysiological value in psoriatic lesion.

PMID- 8138029
TI  - Solubilization, characterization and photoaffinity labeling of the mitochondrial
      dihydropyridine receptor from bovine adrenal medulla.
AB  - 1. The mitochondrial dihydropyridine receptor was solubilized with Chaps at a
      detergent/protein ratio of 2.5, during 45 min at 4 degrees C. 2. From the rate
      constants of association (8.10 +/- 0.25 x 10(4) M-1 min-1) and dissociation
      (0.022 +/- 0.001 min-1) a Kd of 275 nM was calculated, while from saturation
      experiments a Kd of 270 +/- 30 nM and a density of receptors of 106 +/- 9 pmol/mg
      protein was obtained. 4. The solubilized receptors are heat-resistant, sensitive
      to the trypsin and to the reduction of disulfide bonds. 5. In native membranes, a
      polypeptide of 50 kDa was specifically photolabelled with [3H]Azidopine.

PMID- 8138030
TI  - Delta-aminolevulinic acid transport in Saccharomyces cerevisiae.
AB  - 1. This work represents the first approach to characterize the transport system
      of haem pathway precursors, such as delta-aminolevulinic acid (ALA), in two
      strains of Saccharomyces cerevisiae, a wild type, D27, and a HEM R+ mutant. 2.
      ALA transport occurs unidirectionally by a sole active system with an apparent KM
      of 0.10 mM, at the optimum pH of 5.0. ALA uptake is influenced by both the carbon
      and nitrogen source; this suggests a rather complex regulation mechanism. 3. This
      transport is not mediated by the general amino acid permease (GAP). 4. ALA uptake
      is strongly inhibited by compounds harboring a methyl-amine terminus suggesting
      that this group is essential for ALA transport; however, the electric environment
      of the carboxylic group may be also important for the interaction between ALA and
      its transporter active site. 5. We have found differences in ALA transport which
      would indicate a different regulation mechanism for this system in both strain
      cells.

PMID- 8138032
TI  - Detection by reversed-phase HPLC of trace amounts of the alpha 113His globin
      chain in a sheep homozygous for a quadruple alpha-globin gene chromosome.
AB  - 1. In sheep alpha alpha 113His and alpha D alpha alpha 113His globin gene
      haplotypes, the percentage gene efficiencies, from the 5' to the 3' end, are
      about 32-18 and 30-14-6, respectively. 2. We previously found that in a alpha
      alpha alpha alpha homozygote there may be a 1-2% alpha 113His chains, which
      however were difficult to resolve from alpha 113Leu chains by CMC chromatography.
      3. We report here the experimental conditions which allowed a neat resolution of
      the 1% alpha 113His chain peak by RP-HPLC. 4. This finding strongly suggests the
      occurrence of the alpha D alpha alpha alpha 113His haplotype where the percentage
      gene efficiencies are 30-(14-5)-1, supporting the existence of a gradient of
      decreasing expression in multiple alpha-globin gene haplotypes.

PMID- 8138031
TI  - Sheep haemoglobin I or beta B13(A10)Gly-->Ser: an example of a CpG mutation in
      vertebrates. Characterization using FAB-mass spectrometry and amino acid
      sequencing.
AB  - 1. The amino acid substitution which characterizes the haemoglobin I variant from
      sheep has been ascertained using a combination of Fast Atom Bombardment mass
      spectrometry and protein sequencing. 2. A Ser for Gly substitution at position 13
      (10 of the A helix) was found in a polypeptide with the overall sequence of the
      beta B globin. 3. On the basis of the nucleotide sequence of the beta B-globin
      gene, a C to T transition occurring on a CpG doublet is considered to be
      responsible for the amino acid substitution. 4. This represents the first
      observation of a variant sheep Hb due to a mutation which is rather common in the
      human genome. 5. Amongst ruminants, serine is normally present at position 13 of
      goat and sheep epsilon II and gamma chains and of bovine gamma chain which had an
      independent and more ancient evolutionary origin than the beta chains.

PMID- 8138033
TI  - Mass spectrometric analysis of rat hemoglobin by FAB-overlapping. Primary
      structure of the alpha-major and of four beta constitutive chains.
AB  - 1. The globin chain components of Sprague-Dawley rat hemoglobin were obtained by
      reverse-phase HPLC which showed the presence of two alpha-chain and four beta
      chains. 2. The accurate molecular weight of each globin chain was determined by
      means of electrospray mass spectrometry. Extensive mass spectrometric analysis on
      several enzymatic digests by fast atom bombardment mass spectrometry (FAB
      overlapping) meant to determine the complete sequence of the alpha-major and of
      the four beta-globins. 3. The primary structure of the alpha-major globin was
      found in agreement with literature data (Garrick et al., 1975 Biochem. J. 149,
      245-258; Chua et al., 1987). 4. Sequence analysis of the four beta-globin chains
      showed that amino acid differences are restricted to two protein portions: the
      region 22-25 and 123-125, the remaining portions of the molecule being unchanged
      in the four globins. Furthermore, all the amino acid replacements correspond to
      single point DNA mutations and (with the exception of the substitution Asp 22-
      >Asn in the beta 2-globin) involve uncharged substitutions.

PMID- 8138034
TI  - Characterization of the type of carbohydrate chains of the higher molecular
      weight (140 kDa) acid phosphatase of the frog liver.
AB  - 1. The higher molecular weight, (HMW, M(r) 140 kDa) acid phosphatase (AcPase) of
      the frog liver (Rana esculenta) was separated into enzymatically active
      components by isoelectric focusing in an immobilized pH gradient and their
      carbohydrate chains were analyzed by specific lectin binding after native
      blotting. 2. The lectin-binding patterns obtained with ConA, WGA, LcH and PNA as
      well as with WGA and PNA after desialylation indicate that the frog liver HMW
      AcPase contains predominantly N-linked complex and/or hybride type carbohydrate
      chains with terminal sialic acid and fucose residues; O-glycosylated enzyme
      components with free and sialic acid substituted Gal-GalNAc sequences were also
      detected.

PMID- 8138035
TI  - Regulation of rat-kidney cortex fructose-1,6-bisphosphatase activity. I. Effects
      of fructose-2,6-bisphosphate and divalent cations.
AB  - 1. The native rat-kidney cortex Fructose-1,6-BPase is differentially regulated by
      Mg2+ and Mn2+. 2. Mg2+ binding to the enzyme is hyperbolic and large
      concentrations of the cation are non-inhibitory. 3. Mn2+ produces a 10-fold rise
      in Vmax higher than Mg2+. [Mn2+]0.5 is much larger than [Mg2+]0.5. At elevated
      [Mn2+] inhibition is observed. 4. Mg2+ and Mn2+ produce antagonistic effects on
      the inhibition of the enzyme by high substrate. 5. Fru-2,6-P2 inhibits the enzyme
      by rising the S0.5 and favouring a sigmoidal kinetics. 6. The inhibition by Fru
      2,6-P2 is released by Mg2+ and more powerfully by Mn2+ increasing the I0.5.

PMID- 8138036
TI  - Regulation of rat-kidney cortex fructose-1,6-bisphosphatase activity. II. Effects
      of adenine nucleotides.
AB  - 1. The native rat-kidney cortex Fructose-1,6-bisphosphatase is differentially
      regulated by adenine nucleotides in the presence of divalent cations. 2. Binding
      of AMP and ADP to the enzyme is co-operative. The inhibition by both nucleotides
      show an uncompetitive mechanism AMP being the most efficient inhibitor. 3. Mg2+
      decreases the inhibition produced by AMP and ADP by enhancing their I0.5 and
      completely annulates the inhibitory effect of ATP. 4. In the presence of Mn2+ ADP
      behaves as an inhibitor but no inhibition is evident with AMP, suggesting the
      existence of different allosteric sites for each nucleotide.

PMID- 8138037
TI  - Interaction of phospholipids with proteins and peptides. New advances IV.
AB  - 1. The review deals with the newest achievements in the field of the various
      interactions between phospholipids and proteins and peptides. 2. Interactions are
      classified according to the hydrophobic, hydrophilic or mixed character of the
      interactive forces. 3. The effect of the interaction on the structure and
      biological activity of the interacting molecular assemblies is also discussed.

PMID- 8138038
TI  - Constitutive expression of TNF-alpha and -beta genes in mouse embryo: roles of
      cytokines as regulator and effector on development.
AB  - 1. Using the RT/PCR method, we examined mRNA expression of several inflammatory
      factors in mouse embryos during mid-late embryonal development. mRNAs of tumor
      necrosis factor (TNF)-alpha, TNF-beta, their receptors (TNF-RI, TNF-RII),
      transforming growth factor (TGF)-beta, were expressed constitutively in most of
      the embryonic tissues. 2. While mRNAs of other factors, interleukin (IL)-1 alpha,
      IL-1 beta, IL-3, IL-6, granurocyte-colony stimulating factor (G-CSF), leukaemia
      inhibitory factor (LIF), and interferon (IFN)-gamma were only limitedly
      expressed. 3. The mRNAs of several complement components (C2, C3, C4, C5) and
      receptors (CR1, CR2) were also detected. Among them, the expression of C3 and CR1
      were prominent. These results strongly support our idea that inflammation-like
      system play an important role to regulate embryogenesis.

PMID- 8138039
TI  - Comparative study on factors regulating the level of oxidative stress toward
      pulmonary nuclei in two different strains of mice.
AB  - 1. The levels of active oxygen formed and thiobarbituric acid reactive substances
      (TBARS) in pulmonary nuclei of A/J strain were higher than those in the nuclei of
      ddY strain, while nuclear alpha-tocopherol level in the lungs of the former
      strain was lower than the the level in the latter strain. 2. Unsaturation index
      (UI) of nuclear fatty acids and oxidative damage to DNA in the lungs of A/J
      strain were higher than those in the lungs of ddY strain. 3. These results
      suggest that the capacity of nuclear active oxygen formation, nuclear alpha
      tocopherol level and UI of nuclear fatty acids in the lungs can be main factors
      to regulate oxidative stress toward the pulmonary nuclei in the two strains of
      mice.

PMID- 8138040
TI  - Effect of 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE) on arachidonic acid
      metabolism in rabbit platelets.
AB  - 1. The effect of 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE) on the
      formation of thromboxane (TX) B2, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)
      and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous
      arachidonic acid in washed rabbit platelets was examined. 2. 13-HPODE inhibited
      TXB2 and HHT formation without affecting 12-HETE production. 3. 13-Hydroxy-9,11
      octadecadienoic acid which was produced rapidly from 13-HPODE, did not suppress
      the formation of TXB2 and HHT, indicating the requirement of the hydroperoxy
      moiety for the inhibitory effect of 13-HPODE on TXB2 and HHT formation. 4.
      Experiments utilizing mannitol and dimethyl sulfoxide (hydroxy radical
      scavengers) revealed that the action of 13-HPODE is not due to hydroxy radicals
      which are expected to be formed from 13-HPODE. 5. These results suggest that 13
      HPODE is a selective inhibitor of platelet cyclo-oxygenase and may have
      functional effects within platelets.

PMID- 8138041
TI  - Amino acid sequences around exofacial proteolytic cleavage sites of band 3 from
      bovine and porcine erythrocytes.
AB  - 1. Amino acid sequences of bovine and porcine band 3, an erythrocyte anion
      transporter, were determined. 2. The sequence of bovine band 3 was positioned to
      residues 519-599 (the numbering is based on human band 3), in which probably 6
      residues were unidentified. 3. Binding site of DIDS (4,4'-diisothiocyanostilbene
      2,2'-disulfonate), a potent anion transport inhibitor, was identified as Lys-539
      in the bovine case. 4. A loop (residues 551-567), which provides exofacial
      proteolytic cleavage sites, contains only 53% homology between human and bovine,
      whereas the residues flanking it on either side are > 84% homologous. 5.
      Furthermore, the loop of porcine band 3 was indicated to consist of a 6 or 7
      residues short peptide as compared with those of other species.

PMID- 8138042
TI  - Purification and characterization of a novel tyrosyl-aminopeptidase from human
      osteoclastomas.
AB  - 1. An aminopeptidase that preferentially releases tyrosine residues from
      synthetic substrates has been purified from human osteoclastomas. This enzyme
      also hydrolyses dipeptides having an N-terminal tyrosine and a hydrophobic
      carboxy-terminal amino acid. 2. The tyrosyl-aminopeptidase consists of two
      identical subunits with M(r)s of about 100,000. 3. The enzyme is a
      metallopeptidase and is inhibited by chelating agents, chloromethylketone
      analogues of hydrophobic amino acids, and bestatin.

PMID- 8138043
TI  - Rapidly growing broiler (meat-type) chickens: their origin and use for
      comparative studies of the regulation of growth.
AB  - 1. Rapidly growing (meat-type) chickens have been intensively selected for over
      50 years and grow up to four times faster than "layer" strains selected for
      reproductive traits. 2. Comparison between these lines are increasingly being
      used to study mechanisms underlying lean tissue growth. 3. Selection for
      increased growth has resulted in some undesirable consequences such as poor
      reproductive performance, excessive fatness, increased skeletal abnormalities and
      ascites. 4. The biochemistry, physiology and molecular biology of these changes
      are reviewed.

PMID- 8138044
TI  - Protein tyrosine phosphorylation in normal rat tissues.
AB  - 1. Exogenous and endogenous tyrosine protein phosphorylation activities were
      examined in soluble and particulate fractions from various normal tissues by
      using poly-[Glu-80Na, Tyr20] and a monoclonal antibody specific for
      phosphotyrosine. 2. Phosphorylation of the exogenous substrate by the particulate
      forms of TPKs was 2- to 10-fold higher than by soluble forms. The activities of
      particulate and soluble enzymes decreased in the following order: spleen >
      (thymus = kidney) > testes > or = (pancreas = liver = brain) > heart. 3. The
      level of endogenous phosphorylation in the tissues decreased respectively in the
      following order: thymus > brain > or = (pancreas = liver) > spleen > testes >
      kidney > heart for the particulate fractions, and spleen > thymus > brain >
      pancreas > or = liver > testes > kidney > heart for the soluble fractions. 4. A
      large number of phosphotyrosine-containing proteins were detected. In addition,
      several phosphotyrosine-containing proteins of similar molecular weight were
      found in different tissues and fractions.

PMID- 8138045
TI  - Mechanism of pepsin-catalyzed aminotranspeptidation reactions.
AB  - 1. The tetrapeptide Ala2-Nph2 (where Nph = p-nitrophenylalanyl) is treated by
      porcine pepsin to study the mechanism of aminotranspeptidation reactions. 2. The
      major initial product is Ala2-Nph and the major transpeptidation products are
      Nph2 and Nph3 accompanied by some Nph, a little Nph4, Ala2-Nph3 and Ala2-Nph4. 3.
      Oligomers of Nph greater than tetramers are formed near the end of the reaction.
      4. In presence of [3H]Nph, no incorporation of Nph into the transpeptidation
      products is observed. 5. 18O-labeling shows extensive incorporation of 18O atoms
      from [18O]water in the carbonyl oxygens of Nph residues.

PMID- 8138046
TI  - Characterization and amino-terminal sequence of phospholipase A2-II from the
      venom of Agkistrodon bilineatus (common cantil).
AB  - 1. Phospholipase A2 was isolated from the venom of Agkistrodon bilineatus by
      Sephadex G-75 and CM-Cellulose column chromatographies. 2. The purified
      phospholipase A2 gave a single band on disc polyacrylamide gel electrophoresis,
      sodium dodecyl sulfate polyacrylamide gel electrophoresis and ODS-HPLC. 3. The
      enzyme preparation had a mol. wt of 14,000, isoelectric point of pH 10.12 and
      possessed 121 amino acid residues. 4. The enzyme hydrolyzed the phospholipids
      phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol and
      phosphatidyl serine. 5. The contraction of mouse diaphragm was inhibited by
      phospholipase A2-II. 6. Phospholipase A2 activity of this preparation was
      inhibited by ethylenediamine tetraacetic acid, ethyleneglycol (beta-aminoethyl)
      N,N,N',N'-tetraacetic acid, p-bromophenacyl bromide or N-bromosuccinimide, but
      not by iodoacetic acid or diisopropyl fluorophosphate. 7. The amino-terminal
      sequence of the PLA2-II was determined.

PMID- 8138047
TI  - Effects of dietary fatty acid composition on glycerophosphate acyltransferase
      activity in rat adipose tissue and liver.
AB  - 1. How source of dietary fat influences glycerophosphate acyltransferase (GPAT)
      activity in homogenates of adipose tissue and liver was determined using 5 rats
      per diet that contained 12% fat from either corn- (CO), high-oleate-safflower
      (HOSO), palm- or high-stearate-oils. 2. Activity was greatest in adipose tissue
      homogenates of rats fed HOSO and CO whereas no treatment effects were observed in
      liver homogenates. 3. No differences in fat pad weights were observed; thus HOSO-
      and CO-diets likely depressed other lipid synthetic rates. 4. Data indicate that
      mono- and diunsaturated fatty acid diets supported greater adipose tissue GPAT
      activity than did saturated fat diets when fed to rats.

PMID- 8138048
TI  - A quantitative method for analysis of radiolabelled proteoglycans synthesized by
      cultured human arterial smooth muscle cells.
AB  - 1. Sulphate labelled proteoglycans (PG) synthesized by cultured human arterial
      smooth muscle cell have been quantified using an improved method based on a
      combination of specific enzymes and ethanol precipitation. 2. The present method
      gives quantitative data of PGs and subclasses allowing batchwise analysis of a
      large number of samples. 3. Approximately 81% +/- 1.7% (mean +/- SD, n = 6) of
      total PGs synthesized by human arterial smooth muscle cells accumulated in
      medium. 4. In cell layer and medium chondroitin sulphate proteoglycan constituted
      65.0% +/- 0.3% and 75.8% +/- 0.7% (mean +/- SD, n = 3), respectively of sulphated
      PGs. 5. Heparan sulphate proteoglycan accounted for 26.8% +/- 0.6% in cell layer
      and 22.6% +/- 0.5% (mean +/- SD, n = 3) in medium of sulphated PGs.

PMID- 8138049
TI  - Amino acid substitutions within the analogous nucleotide binding loop (P-loop) of
      aminoglycoside 3'-phosphotransferase-II.
AB  - 1. Oligonucleotide-directed mutagenesis of APH(3')-II was used to investigate the
      functions of key amino acids in the P-loop analogous motif of the enzyme. 2. The
      mutations of Gly205-->Glu, Gly210-->Ala and Arg211-->Pro considerably reduced the
      resistance of the resulting strains to KM and to related drugs, e.g. G418. 3.
      Similarly, enzyme activity in the crude extracts of these mutants was
      substantially reduced as well as the enzyme's affinity for Mg2+ ATP. 4.
      Alternatively substitutions at a highly conserved basic residue (Arg211-->Lys and
      Arg211-->His) were not sufficient for the enzyme to sustain the activity at a
      level comparable to that of the wildtype. 5. Moreover, an Arg211-->His mutation
      drastically reduced affinity of the enzyme for Mg2+ ATP. 6. This argues the
      importance of Arg211 residue in contributing to the formation of the P-loop
      structure in addition to its involvement in phosphoryl transfer reaction. 7.
      Computer analysis of the secondary structure predicted that the APH(3')-II loop
      connects a beta-strand to an alpha-helix and that the above mutations caused
      varying degrees of structural distortions at the corresponding regions of the
      protein.

PMID- 8138050
TI  - The response of brown adipose tissue mitochondrial glycerolphosphate
      acyltransferase to cold-exposure in hypothyroidism, after adrenalectomy and after
      treatment with cycloheximide.
AB  - 1. Exposure to cold has previously been shown to considerably increase the
      activity of the mitochondrial form of glycerolphosphate acyltransferase (GPAT) in
      brown adipose tissue (A. C. Darnley, C. A. Carpenter and E. D Saggerson, Biochem.
      J. 253, 351-355, 1988; J. R. D. Mitchell and E. D. Saggerson. Biochem. J. 277,
      665-669, 1991). 2. Both adrenalectomy and chemically-induced hypothyroidism
      increased mitochondrial GPAT activity in rats maintained at 21 degrees C. This
      increase was similar to that caused by exposing rats to the cold (4 degrees C)
      for three days. Whereas exposure of hypothyroid rats to cold (4 degrees C)
      resulted in a further increase in GPAT activity, no further increase in activity
      was observed after exposure of adrenalectomized rats to the cold. 3.
      Administration of triiodothyronine (T3) to rats maintained at 21 degrees C had no
      effect on mitochondrial GPAT activity. 4. Prior treatment with cycloheximide
      abolished 60-70% of the increase in GPAT activity caused by cold-exposure.

PMID- 8138051
TI  - The formation of a dimeric product of raffinose by the action of galactose
      oxidase.
AB  - 1. Galactose oxidase is known to catalyze the oxidation of the C-6 hydroxymethyl
      group of galactose to an aldehyde group. 2. When the products of a galactose
      oxidase-catalase treatment of raffinose were examined by gel filtration and ion
      exchange chromatography, we found that in addition to the expected 6"
      aldehydroaffinose, two other components were present. 3. One component was
      neutral and had an elution volume close to that of maltopentaose and on treatment
      with sodium borohydride or hypoiodite, this component was converted to raffinose
      or 6"-carboxyraffinose, respectively. 4. Fast atom bombardment mass spectroscopy
      in the negative mode indicated that the major molecular ion had an M/Z of 1003.
      5. These data are consistent with this component being a dimer of 6"
      aldehydoraffinose.

PMID- 8138052
TI  - Purification, characterization and biological activities of phospholipase A from
      Russell's viper (Vipera russelli) venom.
AB  - 1. The major phospholipase A has been purified to electrophoretic homogeneity
      from the venom of Vipera russelli (Russell's viper). 2. The molecular weight of
      the purified enzyme was estimated to be 31,000 by Sephadex G-75 gel filtration
      chromatography and 29,000 by SDS-polyacrylamide gel electrophoresis. The enzyme
      exhibited an apparent Km value of 2.3 x 10(-2) M. 3. The phospholipase A showed
      edema forming, indirect hemolytic and myonecrotic activities but not hemorrhagic
      activity.

PMID- 8138053
TI  - Effect of thimerosal on cytosolic calcium and phosphatidylserine synthesis in
      Jurkat T cells.
AB  - 1. We investigated the effect of the thiol reagent, thimerosal on calcium
      movements in the Jurkat T cell line. 2. Thimerosal induced a rise in cytosolic
      Ca2+ concentration due both to a release of Ca2+ from intracellular stores and a
      Ca2+ influx. 3. Thimerosal, released Ca2+ from the same intracellular stores than
      CD3 mAb and ionomycin. 4. Emptying the Ca2+ intracellular stores was accompanied
      by a marked decrease of phosphatidylserine synthesis indicating that
      phosphatidylserine synthesis occurs within or close to the endoplasmic reticulum
      Ca(2+)-stores as previously described in CD3-, ionomycin- or Ca(2+)-ATPase
      inhibitor-treated lymphocytes.

PMID- 8138054
TI  - What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from
      recent advances made in understanding the proinsulin-processing mechanism.
AB  - Pancreatic beta-cell dysfunction is a characteristic of non-insulin-dependent
      diabetes mellitus (NIDDM). An aspect of this dysfunction is that an increased
      proportion of proinsulin is secreted, but an actual beta-cell defect that leads
      to hyperproinsulinemia is unknown. Nevertheless, an impairment in beta-cell
      proinsulin conversion mechanism has been suggested as the most likely cause.
      Insulin is produced from its precursor molecule, proinsulin, by limited
      proteolytic cleavage at two dibasic sequences (Arg31, Arg32 and Lys64, Arg65).
      Two endopeptidase activities catalyze this cleavage: PC2 and PC3. PC2
      endopeptidase cleaves predominately at Lys64, Arg65, and PC3 endopeptidase
      cleaves at Arg31, Arg32. The recent identification and characterization of these
      endopeptidases has enabled a better understanding of the human proinsulin
      processing mechanism. In particular, experimental evidence suggests that the
      majority of human proinsulin processing is sequential. PC3 cleaves proinsulin
      first to generate a proinsulin conversion intermediate that is the preferred
      substrate of PC2. Both PC2 and PC3 activities are influenced by Ca2+ and pH, but
      the more stringent Ca2+ and pH requirements of PC3 suggest it as the most likely
      enzyme to regulate proinsulin conversion, as well as initiate it. When an
      increased demand is placed on the proinsulin-processing mechanism by a glucose
      stimulated increase in proinsulin biosynthesis, there is a coordinate increase in
      PC3 biosynthesis (but not in PC2). This supports PC3 as the key endopeptidase
      that regulates proinsulin processing. In this perspective, the current concepts
      of the enzymology and regulation of proinsulin conversion at a molecular level
      are reviewed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138055
TI  - Poly I:C induction of alpha-interferon in the diabetes-prone BB and normal Wistar
      rats. Dose-response relationships.
AB  - Although the administration of a fixed dose of the alpha-interferon (alpha-IFN)
      inducer, polyinosinic polycytidilic acid (poly I:C), accelerates the development
      of diabetes in DP-BB rats, no reports have characterized the dose-response
      relationship of poly I:C with serum alpha-IFN levels and the development of
      diabetes. This study examines the dose-response relationships of poly I:C with
      the induction of serum alpha-IFN and the development of diabetes in DP-BB and
      normal Wistar rats. Also tested in this study is the hypothesis that the lack of
      development of diabetes in poly I:C-treated normal Wistar rats is attributable to
      a deficient alpha-IFN response. Using poly I:C doses of 0.5, 1.5, 5, and 10
      micrograms/g body weight, a direct dose-response relationship was observed in DP
      BB rats with the serum alpha-IFN response. Moreover, all doses of poly I:C
      accelerated the onset of diabetes in BB rats. Serum alpha-IFN levels inversely
      correlated with time of onset of diabetes (P < 0.01). Also, BB rats with higher
      levels of serum alpha-IFN were associated with earlier onset of diabetes (P <
      0.001). Poly I:C-induced serum alpha-IFN levels were significantly lower in
      diabetic than in nondiabetic BB rats. In normal Wistar rats, although all doses
      of poly I:C significantly increased serum alpha-IFN levels, diabetes was not
      induced. The results of this study indicate that poly I:C administration elevates
      serum alpha-IFN and accelerates the development of diabetes in BB rats at even
      very low doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138056
TI  - Insulin gene transcription is decreased rapidly by lowering glucose
      concentrations in rat islet cells.
AB  - Glucose is the main physiological regulator of insulin biosynthesis and
      secretion. To exert an effect on biosynthesis, stimulatory concentrations of
      glucose act on insulin gene expression at both transcriptional and
      posttranscriptional levels. The relative importance of these two effects is
      controversial. Studies on the effect of decreasing glucose concentrations in
      vitro have been contradictory as to its rapidity and magnitude. We have
      investigated whether a decrease in glucose concentrations from a stimulatory (11
      mM) to a nonstimulatory (2 mM) level regulates insulin gene expression in both
      isolated rat islets and INS-1 cells, an insulinoma-derived cell line that retains
      a number of the differentiation characteristics of native beta-cells. We show
      that, in the presence of a nonstimulatory concentration of glucose, insulin mRNA
      levels decrease rapidly in both rat islets and INS-1 cells. Low glucose decreases
      insulin gene expression at the transcriptional level, and this effect is mediated
      by DNA sequences present within 254 base pairs of the 5'-flank of the rat insulin
      I gene. We conclude that lowering glucose from 11 to 2 mM decreases insulin mRNA
      rapidly by a transcriptional effect.

PMID- 8138057
TI  - Protection against adoptive transfer of autoimmune diabetes mediated through very
      late antigen-4 integrin.
AB  - The very late antigen-4 (VLA-4) integrin expressed on the surface of lymphocytes
      and macrophages can regulate their migration to inflammatory sites as well as
      control cellular activation. The role of VLA-4 in the establishment of autoimmune
      diabetes is not easily predicted given the multiplicity of adhesion pathways and
      their differential use by various cell types. The contribution of VLA-4 to
      insulin-dependent diabetes mellitus was investigated by administration of VLA-4
      specific monoclonal antibodies (MoAb) in an adoptive transfer model of disease in
      NOD mice. This study shows that VLA-4-specific MoAbs profoundly inhibit the
      development of diabetes with protection sustained by repeated MoAb exposure.
      Insulitis was completely inhibited during treatment and progressed to a severe
      degree once MoAb treatment was suspended, yet approximately 40% of treated
      recipients failed to become diabetic during 1-2 months post-treatment. Although
      we cannot rule out depletion of a relatively minor subpopulation of cells by
      prolonged anti-VLA-4 MoAb exposure, this inhibition of diabetes onset by
      treatment with MoAbs to VLA-4 supports a dependence on VLA-4 for cellular
      functions leading to diabetes and demonstrates that a significant disease
      modifying effect can be mediated by targeting the VLA-4 integrin.

PMID- 8138058
TI  - Tissue and plasma concentrations of amidated and glycine-extended glucagon-like
      peptide I in humans.
AB  - Using specific radioimmunoassays, we studied the occurrence of amidated and
      glycine-extended glucagon-like peptide I (GLP-I) molecules in the human small
      intestine and pancreas and in the circulation system in response to a breakfast
      meal. Through gel permeation chromatography of extracts of the human pancreas (n
      = 5), we found that 71% of the GLP-I immunoreactivity eluted as a large molecule
      corresponding to the major proglucagon fragment, 24% corresponded to GLP-I 1-36
      amide, and 5% to GLP-I 1-37. By gel permeation chromatography of extracts of
      human small intestine (n = 6), we found that all immunoreactivity eluted in one
      peak at the common elution position of the two insulin-releasing peptides, GLP-I
      7-36 amide and GLP-I 7-37. Of the GLP-I immunoreactivity, 80% corresponded to GLP
      I 7-36 amide and 20% to GLP-I 7-37. The mean concentrations of amidated GLP-I and
      glycine-extended GLP-I in fasting plasma were 7 +/- 1 and 6 +/- 1 pM,
      respectively (n = 6). In response to a breakfast meal, the concentration of
      amidated GLP-I rose significantly amounting to 41 +/- 5 pM 90 min after the meal
      ingestion, whereas the concentration of glycine-extended GLP-I only rose slightly
      to a maximum of 10 +/- 1 pM. Thus, both amidated and glycine-extended GLP-I
      molecules are produced in the small intestine and in the pancreas in humans. Both
      amidated and glycine-extended GLP-I are measurable in fasting plasma.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138059
TI  - Saturated fatty acid-induced insulin resistance in rat adipocytes.
AB  - Palmitate has been shown to stimulate glucose transport, translocation of GLUT4
      and insulin receptor autophosphorylation in isolated rat adipocytes (Biochem
      Biophys Res Commun 177:343-49, 1991). Here we further characterize the ability of
      short-term treatment with free fatty acids to stimulate glucose transport in
      isolated rat adipocytes and demonstrate that prolonged treatment induces insulin
      resistance. Treatment of adipocytes for 15 min with 1 mM myristate (14:0),
      palmitate (16:0), or stearate (18:0) stimulates glucose transport by 119 +/- 33,
      89 +/- 29, and 114 +/- 30%, respectively. In contrast, oleate (cis 18:1), 1),
      elaidate (trans 18:1), and linoleate (cis 18:2) do not stimulate glucose
      transport. Palmitate stimulates glucose transport in a concentration-dependent
      manner, demonstrating saturation at 1 mM and half-maximal stimulation at 0.25-0.5
      mM. Prolonged treatment (4 h) of rat adipocytes with 1 mM palmitate induces
      insulin resistance. After a 4-h preincubation with palmitate (1 mM), insulin
      stimulates glucose transport in rat adipocytes by 4.4-fold +/- 0.8, vs. 8.8-fold
      +/- 0.8 in controls (n = 3). Palmitate-induced resistant cells demonstrated a 40%
      inhibition in maximal insulin responsiveness with little change in insulin
      sensitivity. Insulin binding is only slightly decreased (8%) in palmitate
      pretreated cells. These studies indicate that saturated fatty acids stimulate
      glucose transport acutely and on prolonged exposure induce insulin resistance via
      a post-insulin binding defect. The underlying molecular mechanisms of insulin
      resistance induced by prolonged treatment with saturated fatty acids may now be
      investigated using this unique cellular model.

PMID- 8138060
TI  - Microalbuminuria precedes the development of NIDDM.
AB  - Several studies have indicated that insulin resistance, elevated blood pressure
      (BP), and dyslipidemia precede the onset of non-insulin-dependent diabetes
      mellitus (NIDDM). Little data, however, exist on the presence of renal disease in
      prediabetic subjects. We measured albumin excretion in a cross-sectional
      population study in subjects 65-74 years of age living in eastern Finland in
      relation to the risk of developing diabetes 3.5 years later. The prevalence of
      microalbuminuria (urinary albumin-to-urinary creatinine ratio > or = 2 mg/mmol)
      was 1.3-, 1.8-, and 2.0-fold higher among subjects with impaired glucose
      tolerance (n = 242), newly diagnosed NIDDM subjects (n = 92), and previously
      diagnosed NIDDM subjects (n = 136), respectively, compared with subjects with
      normal glucose tolerance (n = 826). Nondiabetic subjects with microalbuminuria
      had multiple abnormalities in cardiovascular risk factors including elevated BP,
      high triglyceride concentration, high insulin concentration, and a low high
      density lipoprotein cholesterol concentration, a cluster of risk factors typical
      for prediabetic individuals. The relationship between microalbuminuria and the
      incidence of NIDDM over the 3.5-year follow-up was studied in 891 subjects who
      were free of diabetes at baseline. Converters to diabetes (n = 69) had a higher
      prevalence of hypertension (68.1 vs. 54.4%, P < 0.05) and a higher prevalence of
      microalbuminuria (43.5 vs. 30.4%, P < 0.05) than nonconverters (n = 822). In
      logistic regression analysis, microalbuminuria predicted the development of NIDDM
      independently of BP level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138061
TI  - Linkage analysis of acute insulin secretion with GLUT2 and glucokinase in Pima
      Indians and the identification of a missense mutation in GLUT2.
AB  - The acute insulin response (AIR), a measure of pancreatic beta-cell function,
      aggregates in families and is a predictor for the development of non-insulin
      dependent diabetes mellitus (NIDDM) in insulin-resistant Pima Indians. To assess
      the genetic components of AIR and NIDDM, polymorphic dinucleotide repeat regions
      in two candidate genes, the liver/islet glucose transporter gene (GLUT2) and the
      glucokinase gene, were evaluated. Sib-pair linkage analyses were performed to
      determine if linkage exists between these marker loci and measurements of AIR and
      NIDDM. No linkage was found between glucokinase and either AIR or NIDDM. Robust
      sib-pair linkage analyses suggest linkage between GLUT2 and acute insulin
      response (P = 0.04), but no linkage was observed with NIDDM. The coding region of
      the GLUT2 gene was screened for mutations using polymerase chain reaction-single
      strand conformation polymorphism analysis. A single base change was identified in
      exon 3 in approximately 5% of the study population, and it constitutes the first
      reported mutation in the human GLUT2 gene. This base change resulted in an amino
      acid substitution (Thr110-->Ile110) in the second membrane-spanning region of the
      GLUT2 protein. No significant association was noted between AIR and the presence
      or absence of the mutation. Thus, this mutation in GLUT2 is unlikely the cause of
      a low AIR in Pima Indians.

PMID- 8138062
TI  - Time courses of changes in hepatic and skeletal muscle insulin action and GLUT4
      protein in skeletal muscle after STZ injection.
AB  - To determine the relative time courses of changes in peripheral and hepatic
      insulin action and skeletal muscle GLUT4 protein levels after a streptozotocin
      (STZ) injection in rats, we performed hyperinsulinemic (14-18 nM), euglycemic
      (7.5 mM) clamps in control (n = 8) and diabetic rats at 1 (n = 7), 3 (n = 8), 7
      (n = 8), and 14 (n = 6) days after intraperitoneal STZ (65 mg/kg). Basal plasma
      glucose concentrations increased from 8.1 +/- 0.2 mM in control rats to 23.5 +/-
      1.2 mM 1 day after STZ (P < 0.01) and remained constant thereafter. Basal plasma
      insulin levels were approximately 35% of control levels in all STZ groups (P <
      0.01). Insulin-stimulated whole-body glucose uptake decreased significantly as
      early as one day after STZ injection (P < 0.01), resulting predominantly from a
      decrease in whole-body glycolysis. Insulin action to suppress hepatic glucose
      output was normal on day 1 after STZ but impaired markedly on day 3 and
      thereafter (P < 0.01). Insulin-stimulated glucose uptake in individual skeletal
      muscles was not altered until day 7 after STZ, and the magnitudes of decreases in
      skeletal muscle insulin action on days 7 and 14 were not fully accounted for by
      the decreases in GLUT4 protein level measured from the same muscles. Our data
      indicate that there is a temporal hierarchy in the development of insulin
      resistance in STZ-induced diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138063
TI  - Incidence of renal failure in NIDDM. The Oklahoma Indian Diabetes Study.
AB  - The incidence of and risk factors for renal failure were determined in 912
      Oklahoma Indians with non-insulin-dependent diabetes mellitus in a follow-up
      study conducted between 1987 and 1990. The incidence rate was 15.7/1,000 person
      years after an average follow-up time of 10.2 years. Among those who had no
      qualitatively positive proteinuria at baseline, the incidence of renal failure
      was 10.3/1,000 person-years compared with 19.3- and 56.2/1,000 person-years,
      respectively, in those with slight and heavy proteinuria at baseline. Fasting
      plasma glucose (FPG) > or = 11.1 mM (200 mg/dl) increased the risk of renal
      failure to 2.9-fold (95% confidence interval [CI] = 1.9-4.6) higher than a level
      < 7.8 mM (140 mg/dl), and twofold (95% CI = 1.4-3.1) higher than a level between
      7.8 (140 mg/dl) and 11.1 mM (200 mg/dl). The hypertensive patient had twice the
      incidence of renal failure than the normotensive subject (rate ratio = 2.1, 95%
      CI = 1.4-3.0). Patients with a lower blood pressure under antihypertensive
      medication had a lower incidence of renal failure than those whose hypertension
      remained uncontrolled with or without use of medication. Significant independent
      risk factors for renal failure, identified from Cox's proportional hazards model,
      were duration of diabetes, FPG, age, hypertension, and insulin use (P < 0.05). In
      patients without proteinuria at baseline, FPG and hypertension were significant
      predictors of renal failure as identified by multivariate analyses, whereas in
      patients who had proteinuria at baseline, insulin use was significant. Thus,
      hyperglycemic and hypertension control are suggested strongly for diabetic
      Oklahoma Indians as potential strategies to prevent the development of renal
      failure.

PMID- 8138064
TI  - Suppression of pentosidine formation in galactosemic rat lens by an inhibitor of
      aldose reductase.
AB  - Recent work from our laboratory revealed a correlation between the degree of
      protein pigmentation in human cataractous lens and the advanced Maillard reaction
      as reflected by pentosidine formation. Although the data suggested a role for
      ascorbate in pentosidine formation in senile cataractous lenses, elevated
      pentosidine levels in diabetic cataracts suggested that glucosylation may be
      involved directly in pentosidine biosynthesis. To clarify this issue, we
      quantified pentosidine in lenses from rats with experimental galactosemia with
      and without aldose reductase inhibitor treatment. At 12 months, pentosidine-like
      fluorescence (335/385 nm) was three to six times higher (P < 0.0001) in water
      soluble and insoluble crystallins of galactosemic compared with nongalactosemic
      rats. Actual pentosidine levels increased shortly after onset of galactosemia.
      Contents in water-insoluble crystallins were 6.32 +/- 2.2 and 1.40 +/- 0.66
      pmol/mg protein in galactosemic and control lenses, respectively (P < 0.001).
      Fluorescence and pentosidine were suppressed to almost control levels upon
      treatment with sorbinil. Incubation experiments showed that pentosidine could
      form slowly from galactose, but much more rapidly from ascorbate and its
      oxidation products. Its formation could be inhibited partly by both reduced and
      oxidized glutathione or epsilon-aminocaproic acid. The requirement of oxygen for
      pentosidine formation suggests that oxidative stress associated with glutathione
      depletion and ascorbate oxidation are plausible mechanisms for rapid pentosidine
      formation upon onset of galactosemia. In contrast, Maillard reaction by
      glycoxidation products may account for the sustained increase in pentosidine.
      Both these events may be linked to the newly recognized pseudohypoxic state of
      cells exposed to high sugar concentrations.

PMID- 8138065
TI  - The contribution of insulin-dependent and insulin-independent glucose uptake to
      intravenous glucose tolerance in healthy human subjects.
AB  - Glucose disposal occurs by both insulin-independent and insulin-dependent
      mechanisms, the latter being determined by the interaction of insulin sensitivity
      and insulin secretion. To determine the role of insulin-independent and insulin
      dependent factors in glucose tolerance, we performed intravenous glucose
      tolerance tests on 93 young healthy subjects (55 male, 38 female; 18-44 years of
      age; body mass index, 19.5-52.2 kg/m2). From these tests, we determined glucose
      tolerance as the glucose disappearance constant (Kg), calculated beta-cell
      function as the incremental insulin response to glucose for 19 min after an
      intravenous glucose bolus (IIR0-19), and derived an insulin sensitivity index
      (SI) and glucose effectiveness at basal insulin (SG) using the minimal model of
      glucose kinetics. To eliminate the effect of basal insulin on SG and estimate
      insulin-independent glucose uptake, we calculated glucose effectiveness at zero
      insulin (GEZI = SG - [SI x basal insulin]). Insulin-dependent glucose uptake was
      estimated as SI x IIR0-19, because the relationship between SI and beta-cell
      function has been shown to be hyperbolic. Using linear regression to determine
      the influence of these factors on glucose tolerance, we found that GEZI was
      significantly related to Kg (r = 0.70; P < 0.0001), suggesting a major
      contribution of insulin-independent glucose uptake to glucose disappearance. As
      expected, SI x IIR0-19 also correlated well with Kg (r = 0.74; P < 0.0001),
      confirming the importance of insulin-dependent glucose uptake to glucose
      tolerance. Although IIR0-19 alone correlated with Kg (r = 0.35; P = 0.0005), SI
      did not (r = 0.18; P > 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138066
TI  - Diminished insulin secretory reserve in diabetic pancreas transplant and
      nondiabetic kidney transplant recipients.
AB  - Although both kidney and pancreas transplantation can restore renal and
      pancreatic endocrine functions, the accompanying immunosuppression may cause
      diminished glucose tolerance in some individuals. Therefore, we determined to
      what extent pancreas transplantation itself and the triple immunosuppressive
      therapy used in pancreas transplant recipients have adverse effects on insulin
      secretory reserve. Beta-cell secretory reserve was assessed by the method of
      glucose potentiation of arginine-induced insulin secretion in 25 normoglycemic
      pancreas recipients, 12 nondiabetic kidney recipients using the same
      immunosuppressive therapy, 3 psoriasis patients treated long term with
      cyclosporine, 5 arthritis patients treated long term with prednisone, and their
      respective sex-, age-, and body mass index-matched control subjects. Levels of
      fasting glucose, HbA1c, and glucose disappearance rates were normal in all
      subjects. During the glucose potentiation study, pancreas recipients had
      significantly less insulin secretion than control subjects (maximal acute
      response [ARmax] = 1,083 +/- 93% vs. 3,938 +/- 355%, P < 0.001). Insulin
      responses were also decreased in kidney recipients (ARmax = 2,296 +/- 290%) vs.
      control subjects (4,691 +/- 554%, P = 0.001) and in psoriasis patients treated
      with cyclosporine (ARmax = 2,153 +/- 390%) vs. control subjects (3,962 +/- 88%, P
      = 0.011), but not as extreme as that seen in pancreas recipients. No
      abnormalities were observed in arthritis patients treated with steroids. We
      conclude that normoglycemic pancreas and kidney transplant recipients receiving
      triple immunosuppressive therapy have diminished beta-cell secretory reserve.
      Because this defect was present in psoriasis patients treated long term with
      cyclosporine, but not in arthritis patients treated long term with prednisone,
      this adverse effect was probably caused in part by cyclosporine.

PMID- 8138068
TI  - Speaking the same language.

PMID- 8138067
TI  - The squatting test. A useful tool to assess both parasympathetic and sympathetic
      involvement of the cardiovascular autonomic neuropathy in diabetes.
AB  - The heart rate responses observed after both squatting and standing are thought
      to be of reflex nature and may be useful to assess the functional integrity of
      parasympathetic and sympathetic nerves in diabetes. In the standard maneuver,
      each subject stood still for 3 min, then squatted down for 1 min, and at last
      stood up during an inspiratory phase. In 10 healthy subjects (25-31 years of
      age), lengthening of the R-R interval during squatting was abolished by atropine,
      whereas propranolol markedly attenuated shortening of the R-R interval at
      standing from squatting. Squatting test (SqT) ratios (SqT vagal [SqTv] = ratio
      between the R-R interval mean before squatting and the longest R-R interval after
      squatting; SqT sympathetic [SqTs] = ratio between the basal R-R interval and the
      shortest R-R interval at standing) were calculated in 558 healthy subjects and
      346 diabetic patients (insulin-dependent diabetes mellitus/non-insulin-dependent
      diabetes mellitus: 103/243). Normal ranges (95 and 99% confidence intervals
      [CIs]) for subjects 20-74 years of age showed a statistically significant
      negative correlation with age. SqTv was outside the 99% CI in 145 (42%) diabetic
      patients and in 7 (1.3%) of the control subjects. The corresponding figures for
      SqTs were 40 and 0.8%, respectively. Age and duration of diabetes had a negative
      influence on SqT ratios. SqT ratios were compared with other reflex tests
      currently used for diagnosis of autonomic neuropathy: deep breathing (DB), lying
      to-standing (LS), Valsalva manuever, and blood pressure change after standing
      (orthostatic hypotension [OH]).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138069
TI  - The self-concept of young people with spina bifida: a population-based study.
AB  - Seventy-nine young people with spina bifida were given a psychological, medical,
      carer and occupational therapy assessment. 79 matched able-bodied young people
      received the psychosocial interview. The disabled group felt themselves to be
      less competent in academic, athletic and social aspects of self-concept, less
      supported by classmates, equally supported by parents and friends and more
      supported by teachers than the able-bodied group. Disabled subjects did not
      discount the importance of any area of personal-social functioning, and
      experienced greater discrepancies between competence and importance in most
      academic, athletic, social and physical appearance aspects of self-concept.
      Disabled girls assigned very high importance to physical appearance. Physical
      appearance was more strongly associated with general self-esteem than any other
      area of self-concept.

PMID- 8138070
TI  - Subtle speech and motor deficits of children with congenital hypothyroid treated
      early.
AB  - This study surveyed the development and functioning of a group of 16 children
      with congenital hypothyroidism who had been followed closely since treatment was
      instituted at an average age of 15.6 days. This group of early-treated young
      children had no deficits in cognitive or adaptive functioning. Some isolated
      motor deficits were found, although results of the Finger-tapping and Marching
      subtests of the Reitan-Indiana battery did not replicate the New England
      Congenital Hypothyroid Collaborative (1985) finding of impaired performance.
      Speech deficits were documented in some. Congenitally hypothyroid children with
      delayed neonatal bone-age performed more poorly on most measures than those whose
      bone-age had been normal at birth.

PMID- 8138071
TI  - Traumatic versus perinatally acquired dysarthria: assessment by means of speech
      like maximum performance tasks.
AB  - The performance of two children with traumatic spastic dysarthria, aged 10 and 14
      years, on maximum performance tasks was compared with that of two closely matched
      children with perinatal spastic dysarthria, and reference groups of five children
      with perinatal spastic dysarthria and five control children with normal speech.
      Results showed that performance of the perinatal spastic children on all three
      tasks was poorer than that of their peers with normal speech. In contrast, the
      traumatic spastic children performed within the normal limits on maximum sound
      prolongation and fundamental frequency range, but their maximum repetition rate
      was extremely slow. The overall low performance of the perinatal spastic children
      could be the result of inadequate motor development in addition to the
      neurological impairment. The traumatic spastic children--with a normal
      developmental history--compensated for their impairment by slowing down their
      speech rate. Therapeutic implications are suggested.

PMID- 8138072
TI  - Early expressive language of severely visually impaired children.
AB  - This paper presents a comparison of the early language of nine blind and nine
      severely visually impaired children, with no other impairments, who were
      recruited from paediatric vision clinics in London and assessed in the second and
      third year of life using the Reynell-Zinkin Developmental Scales. Further
      information on milestones and content of early expressive language was obtained
      from parents' diary recordings of their children's emerging words. It is
      concluded that severely visually impaired children's expressive language tends to
      develop later than that of sighted children. The effect of children having even a
      small amount of vision could be discerned in their early words. The developmental
      course appears to be particularly variable for blind children, with implications
      for parental counselling.

PMID- 8138073
TI  - Postural control in sitting the SAM system: evaluation of use over three years.
AB  - The most appropriate posture in which to support the person with severe
      disability and diverse symptoms as a result of complex pathology remains more a
      matter of opinion than the result of research. This work reviews some of the
      studies which have attempted to identify definitive criteria for seating in such
      cases. Factors relating to measurement and conditions which threaten to
      invalidate the results of research in this field are highlighted. A description
      of the Seating and Mobility (SAM) system is given, together with a report of the
      monitoring of nine children with cerebral palsy using the system for a period of
      three years. The difficulties inherent in this work are noted and questions for
      future considerations are raised.

PMID- 8138074
TI  - Physiotherapy for young people with movement disorders: factors influencing
      commencement and duration.
AB  - A questionnaire sent to the parents of 105 patients aged between nine and 20
      years with movement disorders was answered by 81 parents. 51 per cent of the
      patients were undergoing physiotherapy, and these had been having physiotherapy
      for almost all of their lives. Patients with lower mobility scores and those with
      both parents participating tended to continue with physiotherapy. Mobility scores
      were less of a determinant for girls than for boys for continuing or
      discontinuing physiotherapy. The diagnosis of cerebral palsy combined with an
      early start to physiotherapy also gave a higher continuation rate.

PMID- 8138075
TI  - In utero brain damage: relationship of gestational age to pathological
      consequences.
AB  - The authors examined the brains of two infants in whom episodes of fetal
      compromise could be accurately correlated with gestational age. A mother who had
      sustained hypotensive shock at 16 weeks gestation gave birth at 20 weeks to a
      stillborn infant whose brain showed cystic necrosis of the lenticular nuclei and
      multifocal polymicrogyria. The brain of a seven-month-old infant born at 33 weeks
      gestation to a mother who had experienced respiratory arrest during her 28th week
      showed thalamic and brainstem necrosis accompanied by diffuse white matter
      gliosis. Review of the literature yielded 10 similar cases. When the insults
      occurred before 24 weeks of gestation, bilateral pallidal necrosis was a constant
      feature. Between 26 and 34 weeks, the common finding was thalamic necrosis, often
      accompanied by brainstem necrosis. These observations should be of assistance in
      determining the timing of gestational insults, and therefore possible clinical
      correlations, in prenatal brain damage.

PMID- 8138076
TI  - Biotinidase deficiency: early neurological presentation.
AB  - Three patients with biotinidase deficiency are described. Two presented at eight
      weeks of age with anticonvulsant-resistant fits, developmental delay and
      hypotonia. Treatment has been effective. The third developed ataxia and alopecia
      at 14 months and died suddenly at 19 months of age. In all three cases the
      diagnosis was not considered quickly enough. Biotinidase deficiency is a
      treatable cause of severe neurological problems.

PMID- 8138077
TI  - Movement disorder after herpes simplex virus encephalitis.

PMID- 8138078
TI  - [Interaction of the respiratory system and thermoregulation in man in conditions
      of high altitude and cold temperature].

PMID- 8138079
TI  - [Ability of gangliosides to improve the functional state of the body and
      normalize the biochemical structure of cell membranes in hypoxia].

PMID- 8138080
TI  - [Neurophysiologic effects of short-term exposure to ultra-low-frequency magnetic
      field].

PMID- 8138082
TI  - [Use of fractal methods for studying the internal structure of EEG].

PMID- 8138081
TI  - [Conceptual model of the Neva inlet ecosystem].

PMID- 8138083
TI  - [Role of urban factors in the expected psychophysiologic effects of global
      environmental and climatic changes].

PMID- 8138084
TI  - [Health status and working capacity of people in conditions of combined effect of
      chemical and climatic factors and development of methods for their improvement].

PMID- 8138085
TI  - [Immunophysiologic and neuroendocrine status of tobacco growers].

PMID- 8138086
TI  - [Mathematical modeling of electric and magnetic fields close to overhead power
      lines].

PMID- 8138087
TI  - [Changes in electroencephalographic parameters during adaptation to cold].

PMID- 8138088
TI  - [Effect of local detoxification on immune response during treatment of chronic
      periodontitis].

PMID- 8138089
TI  - [Individual behavioral strategy in interpersonal interactions].

PMID- 8138090
TI  - [Systems analysis of the effect of pathogenic environmental factors on the
      neurologic status of the population].

PMID- 8138091
TI  - [Seasonal changes in parameters of the cardiorespiratory system in inhabitants of
      the Russian North].

PMID- 8138092
TI  - [Restructuring of the interaction of EEG components over the course of the day in
      man's adaptation to high altitude].

PMID- 8138093
TI  - [Physiologic mechanisms of respiration and thermoregulation in the early stage of
      adaptation to cold temperature].

PMID- 8138094
TI  - [Parameters of water-salt metabolism in various chronic diseases and under
      extreme working conditions].

PMID- 8138095
TI  - [Adaptive modification of lipid-protein structure of membranes during exposure to
      climatic-geophysical factors of high-altitude].

PMID- 8138096
TI  - [Heterophasic model of lipid peroxidation and the role of transitional metals].

PMID- 8138097
TI  - [Ecologic and physiologic aspects of work activity in conditions of high
      altitude].

PMID- 8138098
TI  - [Adaptive changes of metabolism and corrective effect of alpha-tocopherol at high
      altitude].

PMID- 8138099
TI  - Experimental Biology 94. Part II. Anaheim, California, April 24-28, 1994.
      Abstracts.

PMID- 8138100
TI  - Changes in plasma and gonadal steroid hormones in relation to the reproductive
      cycle and the sex inversion process in the protandrous seabass, Lates calcarifer.
AB  - Plasma and gonadal levels of several gonadal steroids (testosterone, 11
      ketotestosterone, androstenedione, 11 beta-hydroxyandrostenedione, 17 beta
      estradiol, and estrone) were measured by RIA in the protandrous seabass, Lates
      calcarifer, throughout an annual reproductive cycle. Twenty to 25 fish were
      killed every month for gonadal and plasma sampling. Very low plasma levels of 11
      ketotestosterone in females (monthly means always less than 75 pg/ml), and of 17
      beta-estradiol (means always less than 68 pg/ml) and estrone (means always less
      than 42 pg/ml) in males did not fluctuate significantly during the cycle.
      Conversely, plasma concentrations of testosterone, estrone, and 17 beta-estradiol
      peaked during vitellogenesis in females (highest mean: 182 +/- 121, 182 +/- 32
      and 598 +/- 369 pg/ml, respectively) and testosterone and 11-ketotestosterone
      peaked during spermiation in males (highest mean: 189 +/- 91 and 223 +/- 94
      pg/ml, respectively). When sex type are compared over the whole cycle, females
      displayed higher 17 beta-estradiol (172 +/- 233.5 pg/ml) and estrone (79.5 +/- 72
      pg/ml) levels than males (57 +/- 7.5 and 44 +/- 62.5 pg/ml, respectively), while
      males had higher 11-ketotestosterone levels (153 +/- 88 pg/ml) and, to a lesser
      extent, higher testosterone levels (128 +/- 82 pg/ml) than females (51.5 +/- 28
      and 91.5 +/- 60 pg/ml, respectively). Transitional fish always exhibit low plasma
      levels for these four steroids (testosterone 56.5 +/- 12.5 pg/ml, 11
      ketotestosterone 59 +/- 23.5 pg/ml, 17 beta-estradiol 65.6 +/- 36 pg/ml, and
      estrone 61 +/- 47.5 pg/ml). Among gonadal androgens, 11 beta
      hydroxyandrostenedione predominated in testes (3.95 +/- 3 ng/g), except during
      spermiation (0.8 +/- 0.5 ng/g), and remained low in ovaries (1.05 +/- 1.4 ng/g).
      No differences were detected in gonads, for testosterone and 11-ketotestosterone
      whatever the sex type, but their concentrations were higher in vitellogenic and
      atretic ovaries. Androstenedione levels were slightly higher in testes (2.21 +/-
      2 ng/g) than in ovaries (1.53 +/- 1.32 ng/g). Transitional gonads always showed
      low concentrations for these four androgens (testosterone 0.66 +/- 1.77 ng/g, 11
      ketotestosterone 0.14 +/- 0.05 ng/g, androstenedione 0.3 +/- 0.34 ng/g, and 11
      beta-hydroxyandrostenedione 0.2 +/- 0.23 ng/g). Gonadal 17 beta-estradiol was
      nearly undetectable in testes (0.06 +/- 0.07 ng/g), low in ovaries (0.42 +/- 0.46
      ng/g), and strikingly high in transitional gonads (2.89 +/- 1.64 ng/g) even at
      the very beginning of sex inversion. This suggests an important role for this
      estrogen in the protandrous sex inversion process in the seabass L. calcarifer.

PMID- 8138101
TI  - Plasma prolactin during the breeding season in adult and immature macaroni
      (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins.
AB  - Plasma prolactin levels were measured in free-living breeding adult and immature
      (pre-breeding) macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua)
      penguins at Bird Island, South Georgia (54 degrees S, 38 degrees W). Macaroni and
      gentoo penguins first breed at 5-6 and 2 years of age, respectively. In adult
      birds, of both species, prolactin was low (< 1.0 microgram. liter-1) during the
      courtship period and then increased during early (gentoo) to mid (macaroni)
      incubation (to 3.9-4.7 and 2.4-3.5 micrograms.liter-1, respectively), remaining
      elevated until the creche period, by which time continuous nest attendance by the
      adults had ceased. This pattern is similar to that seen in other altricial
      species and is consistent with delayed onset of brood patch development and full
      incubation efficiency, which has been previously reported in penguins. Adult
      female macaroni penguins showed a marked, but transient, increase in prolactin
      concentrations within 24 hr of the first egg being laid (from 1.7 to 7.0
      micrograms.liter-1), plasma levels decreasing following clutch completion (to
      prelaying levels) before increasing again during incubation. Elevated plasma
      prolactin levels occurred in all age classes of immature (nonbreeding) birds in
      both macaroni (1- to 5 year-olds) and gentoo (1-year-olds) penguins. However,
      compared to that in adult birds, the increase in prolactin was more transient in
      immatures, a smaller proportion of immatures had detectable prolactin levels at
      each stage of the breeding cycle, and, at least in 1- and 2-year-olds, absolute
      levels of prolactin were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138102
TI  - Influence of photoperiod and temperature on serum melatonin in the diamondback
      water snake, Nerodia rhombifera.
AB  - Serum melatonin concentrations in the diamondback water snake, Nerodia
      rhombifera, were measured with a radioimmunoassay to determine the influence of
      photoperiod and temperature on melatonin levels. A diel cycle of serum melatonin,
      with elevated concentrations during scotophase, occurred in snakes acclimatized
      for 2 weeks to a 12L:12D photoperiod and 25 degrees. This cycle persisted in
      snakes acclimatized to a reverse photoperiod, with a longer duration of elevated
      scotophase levels. In snakes acclimatized to a normal 12L:12D photoperiod and 10
      degrees, photophase serum melatonin concentrations were lower than at 25 degrees,
      and there was no increase during scotophase. Snakes acclimatized to a normal
      12L:12D photoperiod and 35 degrees had lower serum melatonin levels than those at
      25 degrees, but this difference was not statistically significant. Photoperiod
      and temperature interact to influence serum melatonin in N. rhombifera, with
      photoperiod affecting the phase and temperature affecting the amplitude of the
      diel melatonin cycle.

PMID- 8138103
TI  - Effects of prolactins on the chromatophores of the tilapia, Oreochromis
      niloticus.
AB  - Using isolated scales and split-fin preparations of the tilapia Oreochromis
      niloticus, the effects of a pair of prolactins of the tilapia Oreochromis
      mossambicus (tPRL177 and tPRL188) and of ovine prolactin (oPRL) on chromatophores
      were studied in vitro. These peptides caused melanosome aggregation and
      dispersion of xanthosomes, especially in the split preparations. Their relative
      effectiveness was as follows: tPRL177 > oPRL > tPRL188. Moreover, tPRL177 at 100
      nM induced a high level of pigment dispersion in cultured xanthophores and
      erythrophores, but tPRL188 at the same concentration did not have this effect. We
      also examined the responses of chromatophores to oPRL in primary cell culture and
      found that xanthophores and erythrophores respond to the peptide by pigment
      dispersion in a dose-dependent manner, whereas cultured melanophores showed
      little aggregation of pigment. In denervated melanophores in the split-fin
      preparations, tPRL177 failed to induce aggregation of pigment. From these
      results, it was concluded that prolactin affects brightly pigmented cells of the
      tilapia directly, but affects melanophores indirectly. Norepinephrine which might
      leak from varicosities of chromatic nerve fibers by virtue of the action of
      prolactin molecules may be responsible for melanosome aggregation.

PMID- 8138104
TI  - Thyroid hormones and putative nuclear T3 receptors in tissues of the ascidian,
      Phallusia mammillata cuvier.
AB  - Thyroid hormones were measured by radioimmunoassay in blood plasma and in
      extracts (butanol/chloroform/ammonia) of pharynx, alimentary canal, and tunic of
      Phallusia mammillata. Other animals were injected with [125I]T3 and its
      distribution in the same tissues was determined from 6 to 48 hr after injection.
      Last, the saturable binding of [125I]T3 to salt-extracted nuclear proteins in the
      pharynx and alimentary canal was studied in vitro. T4 was found in all tissues
      examined and in the same order of magnitude (2.7 to 8.4 ng/g) whereas plasma
      concentration was low (0.2 ng/ml). Tissue T3 concentrations were always much
      lower than T4 tissue concentrations, being highest in alimentary canal (0.8-1.1
      ng/g) and very low in the tunic as well as in plasma, in which T3 was generally
      below 0.02 ng/ml. The tissue distribution of [125I]T3 was correlated with T3
      concentrations. Tissue/plasma ratios were approximately 10 in the alimentary
      canal, 5 in the pharynx, and 0.18 in the tunic. Saturable binding of T3 to
      nuclear proteins in the alimentary canal and pharynx was demonstrated. The
      affinity (Kd) was similar to that found in tissues from other chordates but the
      maximal binding capacity was much lower. The very low levels of plasma T3 and low
      T3/T4 ratios may indicate that the endostyle releases primarily T4 into the body
      fluid. On the other hand, the high levels of T3 and the high T3/T4 ratios in the
      alimentary canal suggest that this metabolically active target tissue is the main
      site of the process of deiodination of T4 into T3, a process which has been
      previously shown in P. mammillata in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138105
TI  - Control of testicular cycles in the song sparrow, Melospiza melodia melodia:
      interaction of photoperiod and an endogenous program?
AB  - Adult male song sparrows, Melospiza melodia melodia, underwent testicular
      development accompanied by increases in plasma levels of follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) regardless of photoperiods tested.
      Although gonadal development progressed rapidly in birds exposed to long days,
      males subjected to short day lengths also showed testicular growth between 90 and
      200 days. Onset of photorefractoriness during exposure to continual long days was
      highly variable among individuals. Short days were not required to regain
      photosensitivity, and thus spontaneous testicular recrudescence occurred in birds
      held on long days for prolonged periods. However, cycles of testicular mass,
      length of cloacal protuberance, and prebasic-type molt in birds held on
      continuous long days became dissociated and were erratic. It males held on short
      days were exposed to 1 long day (18L 6D) and then returned to short days, a rapid
      increase in testicular mass and plasma levels of LH and FSH followed. The effect
      of 1 long day was greater if males had been exposed to short days for 2 months or
      longer. Thus, although short days were not absolutely required for dissipating
      photorefractoriness, they apparently accelerate the process. Female song sparrows
      showed a similar response to 1 long day. Input from changing day length was also
      important for triggering testicular regression. Male song sparrows held on 16L 8D
      for 10 months showed no signs of prebasic molt or testicular regression. When
      half of the males in this group were then exposed to 14L 10D (a shorter day
      length but still photostimulatory in spring), there were rapid declines in testis
      mass and FSH levels. These results are consistent with the phenomenon of
      "relative photorefractoriness," in which decreased day length results in gonadal
      regression despite the fact that similar day lengths would have been
      photostimulatory earlier in spring. It is suggested that song sparrows have
      "programs" of gonadal activity and molt that are not usually expressed in
      captivity as part of a complete cycle. The annual change in day length may act to
      drive the cycle, as continual environmental input for entraining endogenous
      programs to exactly 1 year and for scheduling the correct temporal sequence of
      events. Such a combination of continual environmental input and endogenous
      rhythms may be widespread.

PMID- 8138106
TI  - Ultrastructural changes in follicle cell-oocyte associations during development
      and maturation of the ovarian follicle in Atlantic croaker.
AB  - Full-grown ovarian follicles of the marine teleost Atlantic croaker
      (Micropogonias undulatus) are unresponsive to steroidal maturation-inducing
      substance (MIS). However, responsiveness to MIS (maturational competence) can be
      induced in vivo or in vitro by brief stimulation with gonadotropin (e.g., human
      chorionic gonadotropin, hCG). The objective of this study was to examine
      ultrastructural changes in follicle cell-oocyte associations related to the
      acquisition of maturational competence and maturation in croaker ovarian
      follicles. Ultrathin sections of lanthanum-infiltrated samples were observed by
      transmission electron microscopy at various points during follicular development
      and hormone-induced maturation: vitellogenic oocytes (< 350 microns), full-grown
      oocytes (350-400 microns), hCG-stimulated (maturationally competent) oocytes,
      hCG/MIS-stimulated (early-maturation, hydrating) oocytes, and ovulated oocytes.
      In general, prior to ovulation, oocyte microvilli made contact with granulosa
      cells, and gap junction-like structures were seen at these points of contact.
      Midvitellogenic follicles (< 350 microns) had relatively high levels of follicle
      cell-oocyte associations and gap junctional contacts, but by late vitellogenesis
      (350-400 microns) these levels had declined markedly. However, high levels of
      intercellular associations and gap junctional contacts were reestablished upon
      induction of maturational competence with hCG, and these levels remained high in
      early-maturation oocytes. These changes seemed to be mainly due to alterations in
      oocyte microvilli length and surface contact with granulosa cells rather than to
      alterations in the numbers of microvilli. However, retraction and disappearance
      of microvilli occurred during ovulation. Therefore, the appearance of
      maturational competence coincided with the reestablishment of heterocellular gap
      junctional contacts in full-grown follicles. One function of these contacts may
      be to allow transfer of maturational signals between the granulosa cells and the
      oocyte during the early stages of follicular maturation.

PMID- 8138107
TI  - Purification and characterization of urotensin II from the brain of a teleost
      (trout, Oncorhynchus mykiss) and an elasmobranch (skate, Raja rhina).
AB  - Peptides related to urotensin II have been isolated in pure form from an extract
      of whole brain of a teleost, the rainbow trout (Oncorhynchus mykiss) and of an
      elasmobranch, the longnose skate (Raja rhina). The primary structure of the trout
      peptide [Gly-Gly-Asn-Ser-Glu-Cys-Phe-Trp-Lys-Tyr-Cys-Val] is similar to that of
      urotensin II peptides isolated from the urophyses of other teleost fish. For
      example, trout urotensin II contains only one amino acid substitution (Thr4-
      >Ser) compared with urotensin II beta 1 isolated from the urophysis of the carp.
      The primary structure of the skate peptide [Asn-Asn-Phe-Ser-Asp-Cys-Phe-Trp-Lys
      Tyr-Cys-Val] is the same as urotensin II isolated from the caudal spinal cord
      region of the dogfish Scyliorhinus canicula. The data provide chemical evidence
      to support the conclusion of earlier morphological studies [Yulis, C. R., and
      Lederis, K. (1988) Gen. Comp. Endocrinol. 70, 301-311) that certain species of
      fish possess an extensive extraurophyseal distribution of urotensin II
      immunoreactive neurons.

PMID- 8138109
TI  - Histochemical distribution of cholinesterase activity in the hypothalamo
      hypophyseal system of the catfish, Heteropneustes fossilis.
AB  - The distribution of cholinesterase (ChE) activity was demonstrated in the
      hypothalamo-hypophyseal system of Heteropneustes fossilis using acetylthiocholine
      iodide as the substrate. Perikarya of neurons in nucleus lateralis tuberis and
      the periventricular region of the infundibular recess showed moderate to strong
      enzyme activity. In the midventral floor of the infundibular recess, the
      ependymal layer contained ChE-positive neurons, some of which contacted the
      ventricle. From these neurons, fine beaded axonal processes were seen to run
      across the fibrous layer close to ChE-positive capillaries. The blood vessels and
      capillaries in the external palisade layer also showed intense enzyme activity.
      The distributional pattern of ChE strongly suggests homology of the region with
      the median eminence of tetrapods. In the pituitary, the neurohypophysis was
      generally free of enzyme activity except for some displaced neurons, pituicytes,
      and capillaries. The hypophyseal blood vessels and capillaries showed strong
      enzyme activity which varied regionally.

PMID- 8138108
TI  - Immunolocalization of steroidogenic enzymes, P450scc, 3 beta-HSD, P450c17, and
      P450arom in the Hokkaido brown bear (Ursus arctos yesoensis) testis.
AB  - Hokkaido brown bears (Ursus arctos yesoensis) are seasonal breeders and the
      profile of their serum testosterone concentrations undergoes annual changes.
      However, precise sites of steroidogenesis in the bear testis have not been
      identified. Therefore, our objective was to localize steroidogenic enzymes by
      immunocytochemistry using polyclonal antibodies generated against steroidogenic
      enzymes of mammalian origin. The steroidogenic enzymes localized were cholesterol
      side-chain cleavage cytochrome P450 (P450scc), 3 beta-hydroxysteroid
      dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase cytochrome P450 (P450c17), and
      aromatase cytochrome P450 (P450arom) as biosynthetic sites of pregnenolone,
      progesterone or androstenedione, androgens, and estrogens, respectively. Testes
      were collected from three adult bears prior to the mating season (April,
      Hokkaido, Japan) and prepared for immunostaining with primary antibodies,
      followed by an avidin-biotin-peroxidase method. P450scc was localized in Leydig
      cells and spermatids. 3 beta-HSD was found only in Leydig cells. P450c17 was
      identified in Leydig cells and spermatids. Finally, P450arom was found in Leydig
      cells and in spermatids that stained very intensely. Therefore, Leydig cells
      appear to be a site of progestin (both delta 4 and delta 5 C21 steroids),
      androgen, and estrogen production, whereas spermatids appear to be a site of
      pregnenolone, androgen, and estrogen production. Immunolocalization of
      steroidogenic enzymes suggests that steroidogenesis may occur not only in Leydig
      cells, but also in spermatids of the Hokkaido brown bear testis prior to the
      mating season. We also suggest that Leydig cells and spermatids are the
      predominant sites of androgen and estrogen synthesis, respectively, in the
      Hokkaido brown bear testis.

PMID- 8138110
TI  - Seasonal changes in osmoregulation, cortisol, and cortisol receptor activity in
      the gills of parr/smolt of steelhead trout and steelhead-rainbow trout hybrids,
      Oncorhynchus mykiss.
AB  - Steelhead and hybrid trout (rainbow trout male, steelhead female) presmolts and
      smolts, Oncorhynchus mykiss, exposed to 30/1000 seawater (SW) for 24 hr
      manifested progressively lower plasma sodium values from December to May. The
      increase in plasma sodium after 24 hr in SW diminished significantly after March,
      with the hybrids (which were heavier in weight than the steelheads) reaching
      their peak osmoregulatory ability in the middle of April, and the steelheads in
      late May. In fresh water there was little difference in plasma osmotic
      concentration but steelhead plasma chloride fell significantly from March 30
      levels to May 23 levels, whereas hybrid plasma chloride levels did not change
      during this time. In steelheads but not hybrids, plasma cortisol correlated
      negatively with plasma sodium of fish exposed 24 hr in SW. However, in both
      steelheads and hybrids, plasma sodium values 24 hr after SW exposure had an
      inverse correlation with cytosol cortisol from the gills. Again, in both
      steelheads and hybrids, plasma values of fish exposed 24 hr in SW correlated
      positively with cytosol receptor activity. In hybrids, the nuclear extract
      receptor activity, Nmax, increased significantly until late March and then
      dropped significantly thereafter. In steelheads, there were no significant
      differences but Nmax followed the same trends as occurred in hybrids. Thus
      seasonal changes in cortisol and cortisol receptors in steelhead occur during
      smoltification and preparation for marine life and suggest an important role for
      cortisol. In hybrids there appears to be a reduction in seasonality.

PMID- 8138112
TI  - Atrial natriuretic peptide suppresses osmotically stimulated plasma arginine
      vasotocin levels in the Pekin duck.
AB  - Plasma arginine vasotocin (AVT) concentrations were measured at 15-min intervals
      in conscious Pekin ducks intravenously infused with 1 M saline at a rate of 0.5
      ml/min for 1 hr. The responses were compared in eight birds, each given in random
      order a polyclonal antiserum against atrial natriuretic peptide (anti-ANP) or
      normal rabbit serum (control). The elevations in plasma osmolalities and sodium
      concentrations and the reductions in hematocrit values caused by the hypertonic
      saline were similar in both conditions. Plasma ANP in the control animals was
      elevated threefold during the saline infusion (from 66.8 +/- 8.8 pg/ml to a peak
      of 193.3 pg/ml), whereas in the same birds treated with specific antiserum,
      circulating ANP concentrations fell to less than 10 pg/ml and remained at this
      level for the duration of the experiment. Plasma AVT concentrations rose steadily
      and significantly from basal levels of 5.8 +/- 0.5 and 5.8 +/- 0.8 pg/ml in the
      control and anti-ANP groups, respectively; however, the concentrations measured
      in the birds with low plasma ANP were consistently higher (P < 0.02) than those
      under the control condition. Furthermore, the sensitivity of AVT release for the
      control birds (0.35 pg/ml per mOsm/kg) was significantly lower (P < 0.001) than
      that in the anti-ANP animals (0.86 pg/ml per mOsm/kg). Elevated plasma ANP may
      suppress osmotically stimulated AVT release during states of vascular volume
      expansion.

PMID- 8138111
TI  - A phorbol ester and calcium ionophore regulate sex steroid and prostaglandin
      release by follicles of the anuran Rana esculenta and the urodele Triturus
      carnifex.
AB  - The aim of this work was to study the relationships among protein kinase C (PKC),
      calcium, prostaglandins (PGs), and sex steroids in follicles of Rana esculenta
      and Triturus carnifex. Follicles, oocytes, and wall cells of follicle (theca and
      granulosa cells) were incubated in vitro with an activator of PKC, phorbol-12
      myristate-13-acetate (PMA), a calcium ionophore (A23187), an antagonist of
      calcium channel, verapamil, PMA + A23187, prostaglandin F2 alpha (PGF2 alpha),
      and prostaglandin E2 (PGE2). Progesterone, androgens, and 17 beta-estradiol were
      assessed in incubation media of follicles and wall cells and PGs in incubation
      media of follicles, oocytes, and wall cells. In both species, PMA increased
      progesterone; A23187 increased progesterone, 17 beta-estradiol, and PGs;
      verapamil decreased progesterone and PGs; PMA + A23187 increased progesterone, 17
      beta-estradiol, and PGs; PGF2 alpha increased 17 beta-estradiol; PGE2 increased
      progesterone. These data suggest that PKC and calcium intervene in the regulation
      of steroidogenesis and PG synthesis by follicles of both R. esculenta and T.
      carnifex; in particular, calcium seems to regulate PGs synthesis, activating an
      enzymatic pathway which does not include PKC.

PMID- 8138113
TI  - Increased VIP and decreased GnRH expression in photorefractory dark-eyed juncos
      (Junco hyemalis).
AB  - Most temperate zone birds show dramatic seasonal cycles in responsiveness to
      light. In the spring the hypothalamo-pituitary-gonadal axis of photosensitive
      birds is stimulated by long days. In the late summer birds no longer respond to
      long days, their gonads regress, and they are said to be photorefractory. After
      several weeks of refractoriness birds regain photosensitivity. During
      refractoriness circulating concentrations of luteinizing hormone are low and
      prolactin levels are high. These fluctuations in peripheral hormones result from
      changes in the brain rather than in the pituitary and/or the gonads. In the
      present study we examined seasonal changes in expression of vasoactive-intestinal
      polypeptide (VIP) and gonadotropin-releasing hormone (GnRH) in the brain of dark
      eyed juncos (Junco hyemalis). Birds were photosensitive and exposed to long
      photoperiod (20:4 LD) for 1 day, 45-60 days, or not at all, or they were
      photorefractory (housed in 20:4 LD). The results indicate that VIP expression was
      similar in all photosensitive birds. However, photorefractory birds had
      significantly higher numbers of VIP-positive neurons in the infundibulum compared
      to photosensitive birds. The number of GnRH-positive neurons in the preoptic area
      was significantly lower in photorefractory birds and significantly higher in long
      term photostimulated birds. These results indicate that the inverse relationship
      between circulating prolactin (released by VIP) and luteinizing hormone (released
      by GnRH) during refractoriness may result from neural changes in VIP and GnRH
      expression, respectively.

PMID- 8138114
TI  - Effects of photoperiod and temperature on gonadal activity and plasma steroid
      levels in an autumn-spawning bitterling, Acheilognathus rhombea, during different
      phases of its annual reproductive cycle.
AB  - The kanehira bitterling, Acheilognathus rhombea, which breeds during autumn in
      the underyearlings and during summer and autumn in the yearlings, was exposed to
      various photoperiodic and temperature regimes during different phases of its
      annual reproductive cycle. In early autumn, gonadal development and increase in
      plasma levels of female estradiol-17 beta (E2) and male testosterone (T) of
      underyearling fish occurred under the short day length condition (12L12D). In
      early winter, gonadal regression (GSI reduction in both sexes, termination of
      vitellogenesis in females, and termination of spermatogonia proliferation in
      males) and decrease in plasma levels of E2 in females and T in males were induced
      by the low-temperature treatment (13 degrees), while gonadal maturity was
      maintained under the moderate temperature (20 degrees). The low temperature did
      not prevent oocyte maturation and ovulation in females and spermiogenesis and
      spermiation in males, indicating that temperature effect on gonadal activity is
      quite different among the maturational stages. The gonadal development of
      yearling fish did not progress during spring, even under the short day length
      condition combined with moderate temperature, which suggests that this species is
      in the refractory period during this season. In early summer, however, the
      autonomous gonadal maturation of yearling fish kept under moderate temperature
      progressed even under the long day length condition (15L9D). It is concluded that
      the causative factor in the initiation of the spawning period of the
      underyearling fish is the short day length in autumn, and that the causative
      factor in the termination of the spawning period is the low temperature in
      winter. An internal factor such as circannual rhythm in the yearlings is probably
      involved in the refractoriness to the photoperiod during spring and the
      subsequent earlier maturation during summer.

PMID- 8138115
TI  - Seasonal plasma levels of luteinizing and steroid hormones in male and female
      domestic ostriches (Struthio camelus).
AB  - Ostriches are low-latitude birds and can be considered to be seasonal breeders.
      However, they are also opportunistic in that they can breed all year round.
      Monthly hormonal plasma concentrations were measured in six female and six male
      domestic ostriches kept at a latitude of 31 degrees 20'N. Measurements were made
      over a year, during which time each female laid an average of 28.7 eggs. Egg
      laying occurred between March and September, with peak numbers in May-June.
      Concentrations of plasma luteinizing hormone (LH) increased in February in both
      sexes and started declining before termination of egg laying. Plasma testosterone
      concentrations in males increased in April, about 2 months after the increase in
      LH. In females, plasma estradiol concentrations peaked in May but were elevated
      from March to August, basically all of the egg-laying period. Plasma hormonal
      changes in the ostriches were gradual and not abrupt, as seen in many wild
      seasonal breeders of higher latitude.

PMID- 8138116
TI  - Immunocytochemical study of the somatolactin cells in the pituitary of Pacific
      salmon, Oncorhynchus nerka, and O keta at some stages of the reproductive cycle.
AB  - Cells of the intermediate lobe of salmonids, homologous to the PAS-positive cells
      of other teleost species, cannot be differentiated by normal staining techniques,
      but can be immunostained with an antiserum against cod somatolactin (SL).
      Immunocytochemical techniques were applied to pituitary sections of two Pacific
      salmon, Oncorhynchus nerka and O. keta. Samples of immature or early maturing
      fish were collected in the Pacific Ocean and from mature spawning fish from
      hatcheries near Seattle and Willard (Washington). SL cells were rather small and
      moderately immunoreactive in immature fish. They were slightly enlarged in the
      early stages of gonadal development and more often contacted the basal lamina
      through processes with terminal swellings, suggesting granule release into
      perivascular spaces. In spawning fish, cells were enlarged and frequently more
      granulated, showing a wide contact with the basal lamina and a proximodistal
      transport of granules. In addition, large and more or less degranulated cells
      were noted, also indicating an active release of SL granules. Spawning females
      tended to have more SL cells than equivalent males. The gradual stimulation of SL
      synthesis and release during sexual maturation suggests that SL may be involved
      in the control of some steps of reproduction as previously shown by the increase
      in SL plasma levels in maturing coho salmon.

PMID- 8138117
TI  - Plasma LH and steroid hormones in King penguin (Aptenodytes patagonicus) during
      the onset of the breeding cycle.
AB  - Temporal changes in plasma levels of luteinizing hormone (LH), testosterone,
      estradiol, and progesterone were measured throughout molt and the onset of
      reproduction in free-living male and female King penguins (Aptenodytes
      patagonicus) at Crozet Island (46 degrees S, 51 degrees E). In both sexes, LH
      concentrations began to rise as soon as molting ended, before the departure for
      refeeding at sea, suggesting that the beginning of reproductive activity is not
      associated with refeeding and/or courtship behavior. LH remained at high values
      throughout courtship and decreased to lower levels during incubation.
      Gonadotrophin secretion covaried with sustained plasma testosterone levels in
      males and increased estradiol and progesterone levels (peaking at copulation) in
      females.

PMID- 8138118
TI  - The antimetamorphic effect of prolactin in the Japanese flounder.
AB  - Prolactin has an antimetamorphic action in amphibian tadpoles. In the Japanese
      flounder, Paralichthys olivaceus, ovine prolactin (oPRL, 100 ng/ml) antagonized
      the stimulatory effect of triiodothyronine (T3, 1 ng/ml) on the resorption of the
      dorsal fin rays of prometamorphic larvae in vitro. Ovine growth hormone (oGH) at
      the same dose was without effect. Injections with oPRL (50 ng/fish, six times)
      into prometamorphic larvae also delayed the resorption of the dorsal fin rays
      without affecting the rates of eye migration and settling, while oGH was again
      without effect. The changes in the expression of both PRL and GH mRNAs in the
      pituitary during metamorphosis were monitored by in situ hybridization using cDNA
      probes. Both PRL and GH genes were increasingly expressed during successive
      metamorphic stages. These results are discussed in light of the possible
      interactions of PRL and GH with thyroid hormones in the control of development in
      the flounder.

PMID- 8138119
TI  - Involvement of growth hormone and prolactin in the induction of vitellogenin
      synthesis in primary hepatocyte culture in the eel, Anguilla japonica.
AB  - Multihormonal effects of bovine growth hormone (GH) and ovine prolactin (PRL) on
      vitellogenin (Vg) synthesis in response to estradiol-17 beta (E2) were
      electrophoretically examined in primary hepatocyte culture in the eel, Anguilla
      japonica. Newly synthesized protein after hormonal treatment was identified as Vg
      by immunoblot and immunoelectrophoresis. A single injection of E2 into
      hypophysectomized eels failed in the induction of Vg synthesis. Similarly, E2
      alone was insufficient to induce Vg synthesis in the culture. On the other hand,
      the combination of E2 with GH and/or PRL markedly stimulated Vg synthesis.
      Neither GH alone nor PRL alone had any effect on the induction of Vg synthesis by
      cultured hepatocytes. Hepatocytes isolated from E2-primed eels also required GH
      or PRL for continuation of Vg synthesis. The highest Vg synthesis occurred at
      doses of 50 ng GH/ml and 1 microgram PRL/ml in the presence of 2 x 10(-6) M E2.
      These results indicate that the multihormonal stimulation of GH and/or PRL as
      well as E2 is essential for the active synthesis of Vg in eels.

PMID- 8138121
TI  - The interrelation between photoperiod, growth hormone, and sexual maturation of
      adult Atlantic salmon (Salmo salar).
AB  - The plasma profiles of growth hormone (GH) in adult male and female Atlantic
      salmon were determined in relation to manipulation of the photoperiod and to the
      development and timing of sexual maturation. Fish were exposed to natural light
      (NL) or NL + 24L:0D additional light over the netpens from January (ALJ) or March
      (ALM) to July. Thereafter, these groups were brought indoors, subdivided, and
      subjected to simulated natural photoperiod (SNP), continuous light (24L), or
      short day (8L). Assay of salmon GH by RIA in monthly plasma samples revealed that
      GH levels were generally < 1 ng ml-1 during January to June and were only
      slightly affected by additional light in January or March. ALJ-24L treatment, and
      to a lesser extent, ALM-24L treatment, was effective in preventing sexual
      maturation, and GH levels of immature fish continued to be < or = 1.5 ng ml-1. On
      the other hand, in sexually maturing fish, GH levels increased to 2-5 ng ml-1
      months prior to ovulation. Short-day photoperiod (8L) from July advanced
      ovulation and spermiation, whereas continuous light from July delayed these
      processes. The timing of the increase of GH levels was shifted in a parallel
      manner, indicating a functional relationship between plasma GH levels and the
      process of sexual maturation.

PMID- 8138120
TI  - Detection of estrogen receptor mRNA in trout pineal and retina: estradiol-17 beta
      modulates melatonin production by cultured pineal photoreceptor cells.
AB  - Pineal photoreceptor cells produce the neurohormone melatonin, a major
      "Zeitgeber" of the organism. This compound is involved in the control of
      development, growth, sexual maturation, and seasonal reproductive cycles. The
      present study reports that the photosensitive pineal organ and the retina of the
      trout express a 3.5-kb mRNA corresponding to the estradiol-17 beta receptor. The
      effects of estradiol-17 beta on melatonin production by cultured pineal
      photoreceptor cells were also studied. Under a light/dark (LD:12/12) cycle, these
      cells maintained a rhythmic secretion of melatonin, with higher amounts being
      released during the dark phase. The amplitude of the rhythm tended to increase
      with time in culture. Application of estradiol-17 beta during the dark phase of
      an LD cycle (i.e., for 12 hr) affected melatonin release in a dose-dependent
      manner; low concentrations (10(-10) to 10(-8) mol/liter) were inhibitory, whereas
      high concentrations (over 10(-7) mol/liter) were stimulatory (when compared to
      the values obtained at 10(-9) mol/liter). When estradiol-17 beta was given
      continuously for several 24-hr LD cycles, the inhibitory effect observed during
      the first dark phase disappeared in subsequent dark periods. In the presence of
      estradiol-17 beta, at concentrations ranging from 10(-10) to 10(-5) mol/liter, a
      high amplitude rhythm in melatonin secretion returned more rapidly than in
      controls. The present results suggest that estradiol-17 beta receptors are
      expressed in the fish pineal and retina and that estradiol-17 beta modulates
      melatonin secretion by cultured pineal photoreceptors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138122
TI  - Thyroxine-binding protein represents the major vitamin D-binding protein in the
      plasma of the turtle, Trachemys scripta.
AB  - Structural homology between the high-affinity thyroxine (T4)-binding protein
      (TBP) in the plasma of the turtle, Trachemys scripta, and vitamin D-binding
      proteins (DBP) of mammals prompted an investigation of plasma vitamin D binding
      in the turtle. Several lines of evidence indicate that the TBP represents the
      primary binding protein for 25-OH-cholecalciferol (D3) in the turtle plasma. D3
      binding protein in whole plasma migrates in the same position as TBP by size
      exclusion chromatography and polyacrylamide gel electrophoresis; it is
      electrophoretically distinct from sex hormone-binding proteins. D3 binding to
      purified TBP alone is enhanced (up to sevenfold) in the presence of plasma
      proteins, including albumin; with this correction, the D3-binding activity of
      plasma corresponds to expected TBP titers. Plasma selectively stripped of TBP by
      affinity chromatography and purified turtle albumin have only trace D3-binding
      activity. Variations in physiological state (thyroidal status, age, and sex)
      previously associated with variable T4 binding (and TBP levels) in T. scripta
      show correlated variability in plasma D3 binding. D3 binding is also highly
      correlated with T4 binding (r = 0.81; P < 0.001) for plasma samples taken from 30
      adults representing 10 different species of Trachemys. D3 binding in plasma
      exhibits a high-affinity site (Ka = 2.3 x 10(8) M-1) and a second lower-affinity
      (Ka = 2 x 10(6) M-1), higher-capacity site; capacities are highly variable.
      Purified TBP has a comparable high affinity (Ka = 2.8 x 10(8) M-1), with a
      capacity close to 1 mol/mol. Binding of T4 and D3 are not competitive, indicating
      separate binding sites for the two ligands; in fact, T4 tends to enhance the
      affinity and the capacity for D3. A single protein in turtle plasma ("TBP/DBP")
      functions in the transport of two different hormones normally served by two
      distinct binding proteins (representing different multigene families) in mammals.
      These results have implications for the mediation of T4 effects on growth.

PMID- 8138123
TI  - Endothelin-like immunoreactivity in midgut endocrine cells of the desert locust,
      Locusta migratoria.
AB  - Endothelin-1-like immunoreactivity has been found in endocrine cells of the
      midgut of the desert locust Locusta migratoria. Several antisera have been
      directed against the whole molecule and its C-terminal sequence. Endothelin-1
      immunoreactive cells are present in the main region of the midgut (ventriculus)
      and in the midgut caeca but not in the ampullae through which the malpighian
      tubules drain. Endothelin-1-like immunoreactivity colocalizes with FMRFa
      immunoreactivity in the cells of the main region of the midgut but not in those
      in the midgut caeca. Endothelin-1-immunoreactive cells are present not only in
      adults but also throughout the five instars of posthatching development.

PMID- 8138124
TI  - Influence of androgen on the GnRH-stimulated secretion and biosynthesis of
      gonadotropins in the pituitary of juvenile female bullfrogs, Rana catesbeiana.
AB  - The influence of androgen on pituitary sensitivity to gonadotropin-releasing
      hormone (GnRH) was investigated in juvenile female bullfrogs. Newly metamorphosed
      bullfrogs were treated in vivo for 7 days or their pituitaries were treated in
      vitro for 24 hr with 5 alpha-dihydrotestosterone (DHT). Pituitary sensitivity to
      GnRH was assessed by incubating glands with 100 ng/ml GnRH. The secretion of
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was quantified by
      separate radioimmunoassays. Gth biosynthesis was quantified using
      immunoprecipitation to measure the incorporation of [35S]methionine. Prior
      exposure to DHT, in vitro or in vivo, significantly elevated the GnRH-induced
      secretion of LH and FSH. However, DHT had a differential influence on the two
      gonadotropins; both the basal and the GnRH-induced secretion of LH was enhanced,
      whereas only the GnRH-induced secretion of FSH was elevated. DHT did not
      significantly alter Gth biosynthesis. Treating older frogs (5 months
      postmetamorphic) in vivo with DHT (for 7 days) combined with a GnRH agonist
      (GnRHa) for 3 days enhanced the GnRH-stimulated Gth biosynthesis compared to
      treatment with either DHT or GnRHa alone. Therefore, while DHT may act on the
      pituitary to enhance gonadotropin secretion in response to GnRH, this action does
      not result in a concomitant increase in Gth biosynthesis. Juvenile female
      bullfrogs may require an increase in both GnRH and DHT in order to stimulate Gth
      biosynthesis.

PMID- 8138125
TI  - Characterization of yeast DNA sequences capable of directing transcription in
      Streptomyces and Escherichia coli.
AB  - Random genomic DNA fragments from Saccharomyces cerevisiae were tested for their
      ability to activate transcription of a promoterless aminoglycoside
      phosphotransferase-encoding gene in Streptomyces. About 10% of the insertions led
      to kanamycin resistance when selected at low concentration (5 micrograms ml-1).
      The nucleotide sequences of five insertions that allowed growth at different
      concentrations of the antibiotic were determined. Three of them contained -10 and
      -35 consensus sequences for the major class of eubacterial promoters. In two
      others, a -10 sequence could be identified, but a -35 element was absent at the
      appropriate distance. All of the five inserts were also transcriptionally active
      in Escherichia coli and therefore probably belong to the major class of
      eubacterial promoters. Three of the characterized insertions found to match known
      yeast sequences did not derive from promoter regions. We conclude that sequences
      that function as eubacterial promoters occur at random in the yeast genome.

PMID- 8138126
TI  - Isolation and biological characterization of staphyloferrin B, a compound with
      siderophore activity from staphylococci.
AB  - A highly hydrophilic compound with siderophore activity has been isolated from
      the supernatant of Staphylococcus hyicus DSM 20459 grown under iron-restricted
      conditions. The metabolite, named staphyloferrin B, is strictly iron-regulated
      and produced by a large variety of staphylococci strains. In vivo iron transport
      measurements and the growth-promoting activity in a bioassay establish
      staphyloferrin B as the second siderophore for staphylococci besides the
      previously described staphyloferrin A. The structure elucidation revealed 2,3
      diaminopropionic acid, citrate, ethylenediamine and 2-ketoglutaric acid as
      structural components of the compound. Thus, staphyloferrin B is a structurally
      new siderophore of the complexone type.

PMID- 8138127
TI  - A PCR-based assay for the identification of the fish pathogen Renibacterium
      salmoninarum.
AB  - By means of a one-step one-tube extraction from less than 1 mg of tissue it is
      possible to identify, via the polymerase chain reaction, Renibacterium
      salmoninarum in salmon with bacterial kidney disease. A 149-bp DNA sequence
      unique to R. salmoninarum was specifically amplified and its nature confirmed by
      Southern hybridization using a non-isotopically labelled probe. The sensitivity
      of the approach allowed the detection of 22 R. salmoninarum cells. The procedure
      was successfully applied in the identification of the causative agent of
      bacterial kidney disease in kidney tissue from infected fishes.

PMID- 8138128
TI  - Purification and cloning of sakacin 674, a bacteriocin from Lactobacillus sake
      Lb674.
AB  - Sakacin 674, a bacteriocin produced by Lactobacillus sake Lb764 and which
      inhibits the growth of Listeria monocytogenes, was purified to homogeneity by
      ammonium sulphate precipitation and sequential ion exchange, hydrophobic
      interaction and reversed phase chromatography. The complete amino acid sequence
      of sakacin 674 was determined by Edman degradation. The bacteriocin consisted of
      43 amino acid residues and had a calculated molecular mass of 4436.6 Da, which is
      in good agreement with the molecular mass of 4437.2 as determined by mass
      spectrometry. The structural gene encoding sakacin 674 (sakR) was located on the
      chromosome. This gene was cloned and sequenced. It encoded a primary translation
      product of 61 amino acid residues which was cleaved between amino acids 18 and 19
      to yield the active sakacin 674. Sakacin 674 resembled other known bacteriocins
      and was very similar to sakacin P.

PMID- 8138129
TI  - Tn 5Map, a transposon for the rapid mapping of restriction sites in plasmids.
AB  - A transposon was constructed allowing the rapid restriction mapping of plasmids.
      This transposon, Tn 5Map, contains a cleavage site for the I-SceI endonuclease
      which recognizes an 18-mer. After in vivo transposition of Tn5Map into the
      plasmid of interest, the plasmid is isolated and linearized with I-SceI.
      Splinkers labelled with digoxygenin and complementary to the left and right end
      of the linearized molecule are added and ligated. After partial digestion of the
      splinkered molecules with the restriction enzyme of interest, separation of the
      cleavage products in an agarose gel, and Southern transfer, the labelled
      fragments are visualized by the addition of the chemiluminescent substrate AMPPD
      and alkaline phosphatase. The restriction map can be directly read from the
      bottom to the top of the gel.

PMID- 8138130
TI  - Growth and adhesion of Enterococcus faecium L-forms.
AB  - Comparisons of growth and surface colonisation of Enterococcus faecium L-forms
      and their cell-walled forms were undertaken to produce information about their
      ability to form sessile cells. The growth of L-forms in liquid culture was slower
      than that of the parent. This was reflected in their longer lag phase and slower
      specific growth rates: 0.16 h-1 for the L-form and 0.81 h-1 for the parent.
      Although E. faecium L-forms attached to a silastic rubber surface, the attached
      population density was 10-100-fold less than that of the parent. Confluent
      biofilms on the silastic surfaces were not observed for either bacterial form.
      Comparison of the attachment of E. faecium L-form and parent may provide
      important information on how bacteria overcome host defence mechanisms and
      antibiotic treatment.

PMID- 8138131
TI  - Alternatives to arginine as energy sources for the non-fermentative Mycoplasma
      gallinarum.
AB  - In contrast to previously studied non-fermentative arginine-hydrolysing (F-/A+)
      Mycoplasma species, M. gallinarum cells suspended in a salts solution oxidised
      ethanol and L-lactic, pyruvic and 2-oxobutyric acids. The organic acids were
      additionally shown effectively to replace arginine as energy sources in growth
      media. However, their presence did not inhibit arginine hydrolysis, nor did
      arginine inhibit organic acid catabolism. The ability to oxidise organic acids is
      a potentially useful diagnostic character enabling sub-division of the F-/A+
      Mycoplasma species. M. gallinarum also differed from previously studied F-/A+
      mycoplasmas in possessing relatively high NADH oxidase activity and producing
      H2O2 as only a minor product of NADH oxidation.

PMID- 8138133
TI  - Transposon Tn5 mutagenesis of pseudomonas fluorescens to isolate mutants
      deficient in antibacterial activity.
AB  - Pseudomonas fluorescens was subjected to insertion mutagenesis studies using the
      transposon Tn5-GM to generate mutants deficient in antibacterial activity minus
      mutants. The transposon located on the temperature-sensitive plasmid pCHR84 was
      conjugally transferred into the non-pathogenic pseudomonad using the triparental
      mating procedure. Random integration of Tn5-GM into the chromosome of P.
      fluorescens was achieved by heat treatment of the transformed cells at 42 degrees
      C. Approximately 2% of transconjugants revealed an auxotrophic phenotype
      indicating efficient integration of the employed transposon into the chromosome
      of P. fluorescens. One transposon insertion mutant was obtained showing an
      antibacterial activity minus phenotype. This mutant (MM-7) was found to be
      defective in the production of an unidentified antibacterial compound against B.
      subtilis. These results introduce Tn5 transposon mutagenesis as a new useful tool
      for the molecular analysis of P. fluorescens.

PMID- 8138132
TI  - Regulation of the rpoN, ORF102 and ORF154 genes in Pseudomonas putida.
AB  - The DNA sequence downstream of the Pseudomonas putida rpoN gene and the adjacent
      ORF102 was determined. This region encodes an ORF (ORF154) whose gene product was
      found to be homologous to a family of phosphotransferases. Insertional
      mutagenesis and analysis of mRNA transcripts showed that the rpoN gene is
      transcribed separately from the two downstream genes. The rpoN promoter was
      localized to an 86 nucleotide-long region upstream of the rpoN gene by
      examination of the expression of a series of rpoN::lacZ fusions. The expression
      of rpoN in P. putida was independent of the nitrogen status of the cell but was 5
      times higher in the rpoN mutant than in the wild-type strain, suggesting that the
      expression of the rpoN gene in this organism is autoregulated.

PMID- 8138134
TI  - Toxic effect on human spermatozoa by Chlamydia trachomatis purified
      lipopolysaccharide.
AB  - We have investigated the effect that lipopolysaccharide extracted from Chlamydia
      trachomatis has on human spermatozoa. A lipopolysaccharide of 0.1 microgram ml-1
      caused a spermatozoa mortality rate of 65 +/- 4% evaluated by eosin exclusion
      test. The toxic activity occurred rapidly even after brief incubation times,
      reaching the maximum (100% mortality) within 60 min.

PMID- 8138135
TI  - The phylogenetic diversity of thermophilic members of the genus Bacillus as
      revealed by 16S rDNA analysis.
AB  - Sixteen thermophilic strains of the genus Bacillus, representing eight validly
      described and six invalidly described species, as well as one unassigned strain,
      were investigated by comparative 16S rDNA analyses and the sequences compared to
      the existing database for the genera Bacillus and Alicyclobacillus. The majority
      of strains were found to cluster in two groups represented by B.
      stearothermophilus and B. pallidus. Bacillus smithii, B. thermocloacae, and B.
      thermoruber are phylogenetically well separated and cluster within the radiation
      of mesophilic bacilli. The as yet undescribed taxon 'B. flavothermus' warrants
      species status. B. schlegelii and B. tusciae group peripherally with members of
      Alicyclobacillus and may be reclassified when more phenotypic data support their
      phylogenetic position.

PMID- 8138136
TI  - Studies on azole-induced cell death in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae strain XL16-5B exhibited a fungicidal response to
      treatment with ketoconazole. Cell death became apparent during prolonged
      treatment over 72 h following an initial period over 24 h where viable cells were
      found and limited cell division occurred. Sterol analysis showed some differences
      between XL16-5B and the strain XY729-5a, which had a fungistatic response to
      ketoconazole. In particular, the level of ergosterol was higher in XL16-5B and
      remained high during treatment.

PMID- 8138137
TI  - Binding of bovine transferrin by Pasteurella multocida serotype B:2,5, a strain
      which causes haemorrhagic septicaemia in buffalo and cattle.
AB  - Pasteurella multocida serotype B:2,5, which causes haemorrhagic septicaemia in
      buffalo and cattle, was examined for the presence of transferrin-binding
      proteins. An 82-kDa iron-regulated outer membrane protein was found which
      specifically binds bovine transferrin. In contrast, P. multocida serotype B:3,4,
      associated with haemorrhagic septicaemia in feral ruminants, did not express
      transferrin-binding proteins. These results might indicate a role for transferrin
      binding in the pathogenesis of haemorrhagic septicaemia in cattle and buffalo.

PMID- 8138138
TI  - The effect on enterotoxicity of protease purified from Vibrio cholerae O1.
AB  - The effect on enterotoxicity of protease purified from Vibrio cholerae O1 was
      investigated by the inoculation of live vibrio cells into protease-treated loops
      of the ileal loop model. Fluid accumulation ratios in the protease-treated loops
      were elevated in a dose-dependent manner by challenge with live vibrio cells but
      not by that with toxin. An enhancement effect of protease on enterotoxicity was
      observed in both serotypes of V. cholerae O1 and V. cholerae non-O1. It is
      suggested, therefore, that the enterotoxicity was enhanced by treatment with
      protease when live vibrio cells were inoculated into the ileal loops of rabbits.

PMID- 8138139
TI  - Identification and sequencing of pyrG, the CTP synthetase gene of Azospirillum
      brasilense Sp7.
AB  - An 18.5-kb DNA fragment carrying the trpGDC cluster of Azospirillum brasilense
      Sp7 was previously cloned, yielding cosmid pAB1005. Attempts to identify trpA in
      the vicinity of trpGDC failed but led to the detection of a locus strongly
      homologous to pyrG, the structural gene for the CTP synthetase. The function of
      the A. brasilense pyrG gene was verified by complementation of the cytidine
      requiring PyrG-deficient mutant JF646 of Escherichia coli. A second open reading
      frame was identified downstream of pyrG. The deduced amino acid sequence showed
      homology to dienelactone hydrolases of Pseudomonas and Alcaligenes, enzymes
      involved in utilization of halogenated aromatic compounds.

PMID- 8138140
TI  - Ability of human sera to neutralise the activity of Vero cytotoxins VT1, VT2 and
      variant forms of VT2.
AB  - Sera, from 17 patients with diarrhoea or haemolytic uraemic syndrome, and six
      healthy adults, were tested for neutralisation of Vero cytotoxins (VT). For all
      17 patients there was evidence of infection with Escherichia coli O157. Sera from
      two controls but from none of the patients neutralised VT1, although two patients
      were infected by strains producing VT1 and VT2. Sera from all six controls and 14
      patients neutralised VT2 derived from strains 933 and E32511, but not variant
      forms of VT2 derived from strains E32511, E57, B2F1 and H.1.8. This neutralising
      activity warrants further investigation, especially as many O157 VTEC carry both
      VT2 and VT2 variant genes.

PMID- 8138141
TI  - Phage type 193 of Salmonella typhimurium contains different chromosomal genotypes
      and multiple IS200 profiles.
AB  - The common phage type 193 of Salmonella typhimurium was analyzed with respect to
      molecular markers of chromosomal genotype. Three profiles of the 16S rRNA genes
      and seven profiles of the DNA insertion element IS200 were found among ten
      representative strains of DT193. The IS200 profiles found within this single
      phage type were highly diverse, confirming that DT193 is a composite phage type
      containing several distinct clones and hybrid lines. IS200 profiling is thus
      appropriate both for primary strain discrimination, and for subdivision within
      certain phage types of S. typhimurium, such as DT193. This rapid molecular
      definition of clonality will be useful for the epidemiological investigation of
      food poisoning outbreaks.

PMID- 8138142
TI  - A spontaneous point mutation in the aac(6')-Ib' gene results in altered substrate
      specificity of aminoglycoside 6'-N-acetyltransferase of a Pseudomonas fluorescens
      strain.
AB  - The aac(6')-Ib' gene from Pseudomonas fluorescens BM2687, encoding an
      aminoglycoside 6'-N-acetyltransferase type II which confers resistance to
      gentamicin but not to amikacin, was characterized. Nucleotide sequence
      determination indicated total identity between aac(6')-Ib' and the aac(6')-Ib
      gene from Pseudomonas aeruginosa BM2656 [1] with the exception of a C-to-T
      transition that results in a serine to leucine substitution at position 83 of the
      deduced polypeptide. The aac(6')-Ib gene specifies a type I enzyme which confers
      resistance to amikacin but not to gentamicin [2]. It thus appears that the point
      mutation detected is responsible for enzymic altered substrate specificity.

PMID- 8138143
TI  - Phylogeny and lipid composition of Thermonema lapsum, a thermophilic gliding
      bacterium.
AB  - 1,490 nucleotides of the 16S rRNA gene of a Gram-negative, thermophilic and
      gliding bacterium, Thermonema lapsum, have been sequenced. Phylogenetic analysis
      indicates that T. lapsum is related to cytophaga-flavobacteria-bacteroides (CFB)
      and is confirmed by the identification signature nucleotides that define this
      group. Further phylogenetic analysis indicates that T. lapsum forms the deepest
      branch in the CFB group; this observation was confirmed by the identification of
      unique nucleotide and nucleotide pairs which separate T. lapsum from all other
      members of this group. The phospholipid fatty acid (PLFA) profile also confirmed
      that T. lapsum is related to the cytophaga-flavobacteria-bacteroides group and
      also to selected members of the genus Flexibacter; the PLFA profile is unique to
      T. lapsum.

PMID- 8138144
TI  - The phylogeny of Mycoplasma bovis as determined by sequence analysis of the 16S
      rRNA gene.
AB  - The nucleotide sequence of the 16S rRNA gene of Mycoplasma bovis has been
      determined. Comparisons with other 16S rRNA sequences of mycoplasmas showed that
      Mycoplasma agalactiae is phylogenetically the closest relative. In total, only
      eight nucleotides differed between the M. bovis and M. agalactiae 16S rRNA
      sequences. The phylogenetic position of M. bovis with respect to other
      mycoplasmas was determined by sequence comparisons and from features in the
      secondary structure of 16S rRNA.

PMID- 8138145
TI  - Study of the influence of plasmids on the arbitrary primer polymerase chain
      reaction fingerprint of Escherichia coli strains.
AB  - To study the effect of plasmids on the arbitrary primer-polymerase chain reaction
      fingerprint of bacterial strains, the Escherichia coli strains DH5, Top10, and
      W3110 were transformed with plasmids of different sizes: respectively, pUC19,
      pCEP and two clinically important plasmids carrying resistance to several
      antibiotics. Total DNA, i.e. both chromosomal and plasmid DNA, was prepared from
      transformed cells by boiling the cell suspensions and by phenol-chloroform
      extraction; chromosomal DNA was prepared by the same methods from the non
      transformed, plasmid-free strains; plasmid DNA of pUC19 was purchased; plasmid
      DNA of pCEP was purified from the transformed strains by caesium chloride density
      gradient centrifugation. Arbitrarily primed polymerase chain reaction was carried
      out for all of these preparations. Amplification carried out independently with
      three different primers resulted in similar patterns for the chromosomal
      preparations whether or not plasmid was present. Amplification of plasmid DNA
      gave different patterns, characterized by fragments larger than those obtained
      when total or chromosomal DNA were used as the target. These data illustrate that
      the plasmids studied here do not influence the chromosomal arbitrarily primed PCR
      fingerprint, although plasmids alone are amplified in the absence of chromosomal
      DNA. Experiments comparing different relative concentrations of plasmid and
      chromosomal DNA indicate that under natural conditions the amount of chromosomal
      DNA per cell is sufficient to inhibit observable amplification of the plasmid(s)
      present.

PMID- 8138146
TI  - Detection of apoptosis induced DNA cleavage in scrapie-infected sheep brain.
AB  - The pathogenesis and molecular basis of nerve cell death which accompanies
      scrapie infections in sheep are not well understood. Degeneration of neurons in
      culture caused by prion protein fragments has recently been reported to be
      consistent with mechanisms of cell death by apoptosis or programmed cell death.
      Apoptosis activation during prion-related encephalopathies has not yet been
      established in vivo. We report here the detection of DNA damage consistent with
      apoptosis in the brain cells of sheep infected with scrapie using laser scanning
      microscopic analysis of the single cell gel assay. We suggest that this DNA
      fragmentation is the result of the activation of the mechanisms characteristic of
      apoptotic cell death.

PMID- 8138147
TI  - Barbara McClintock (June 16, 1902-September 2, 1992).

PMID- 8138149
TI  - Allozymes in evolutionary genetics: self-imposed burden or extraordinary tool?

PMID- 8138148
TI  - Inactivation of the Neurospora crassa gene encoding the mitochondrial protein
      import receptor MOM19 by the technique of "sheltered RIP".
AB  - We have used a technique referred to as "sheltered RIP" (repeat induced point
      mutation) to create mutants of the mom-19 gene of Neurospora crassa, which
      encodes an import receptor for nuclear encoded mitochondrial precursor proteins.
      Sheltered RIP permits the isolation of a mutant gene in one nucleus, even if that
      gene is essential for the survival of the organism, by sheltering the nucleus
      carrying the mutant gene in a heterokaryon with an unaffected nucleus.
      Furthermore, the nucleus harboring the RIPed gene contains a selectable marker so
      that it is possible to shift nuclear ratios in the heterokaryons to a state in
      which the nucleus containing the RIPed gene predominates in cultures grown under
      selective conditions. This results in a condition where the target gene product
      should be present at very suboptimal levels and allows the study of the mutant
      phenotype. One allele of mom-19 generated by this method contains 44 transitions
      resulting in 18 amino acid substitutions. When the heterokaryon containing this
      allele was grown under conditions favoring the RIPed nucleus, no MOM19 protein
      was detectable in the mitochondria of the strain. Homokaryotic strains containing
      the RIPed allele exhibit a complex and extremely slow growth phenotype suggesting
      that the product of the mom-19 gene is important in N. crassa.

PMID- 8138150
TI  - Meiotic mutants that cause a polar decrease in recombination on the X chromosome
      in Caenorhabditis elegans.
AB  - Recessive mutations in three autosomal genes, him-1, him-5 and him-8, cause high
      levels of X chromosome nondisjunction in hermaphrodites of Caenorhabditis
      elegans, with no comparable effect on autosomal disjunction. Each of the mutants
      has reduced levels of X chromosome recombination, correlating with the increase
      in nondisjunction. However, normal or elevated levels of recombination occur at
      the end of the X chromosome hypothesized to contain the pairing region (the left
      end), with recombination levels decreasing in regions approaching the right end.
      Thus, both the number and the distribution of X chromosome exchange events are
      altered in these mutants. As a result, the genetic map of the X chromosome in the
      him mutants exhibits a clustering of genes due to reduced recombination, a
      feature characteristic of the genetic map of the autosomes in non-mutant animals.
      We hypothesize that these him genes are needed for some processive event that
      initiates near the left end of the X chromosome.

PMID- 8138151
TI  - The generation and genetic analysis of suppressors of lethal mutations in the
      Caenorhabditis elegans rol-3(V) gene.
AB  - The Caenorhabditis elegans rol-3(e754) mutation is a member of a general class of
      mutations affecting gross morphology, presumably through disruption of the
      nematode cuticle. Adult worms homozygous for rol-3(e754) exhibit rotation about
      their long axis associated with a left-hand twisted cuticle, musculature, gut and
      ventral nerve cord. Our laboratory previously isolated 12 recessive lethal
      alleles of rol-3. All these lethal alleles cause an arrest in development at
      either early or mid-larval stages, suggesting that the rol-3 gene product
      performs an essential developmental function. Furthermore, through the use of the
      heterochronic mutants lin-14 and lin-29, we have established that the expression
      of rol-3(e754)'s adult specific visible function is not dependent on the presence
      of an adult cuticle. In an attempt to understand rol-3's developmental role we
      sought to identify other genes whose products interact with that of rol-3. Toward
      this end, we generated eight EMS induced and two gamma irradiation-induced
      recessive suppressors of the temperature sensitive (ts) mid-larval lethal
      phenotype of rol-3(s1040ts). These suppressors define two complementation groups
      srl-1 II and srl-2 III; and, while they suppress the rol-3(s1040) lethality, they
      do not suppress the adult specific visible rolling phenotype. Furthermore, there
      is a complex genetic interaction between srl-2 and srl-1 such that srl-2(s2506)
      fails to complement all srl alleles tested. These results suggest that srl-1 and
      srl-2 may share a common function and, thus, possibly constitute members of the
      same gene family. Mutations in both srl-1 and srl-2 produce no obvious
      hermaphrodite phenotypes in the absence of rol-3(s1040ts); however, males
      homozygous for either srl-1 or srl-2 display aberrant tail morphology. We present
      evidence suggesting that the members of srl-2 are not allele specific with
      respect to their suppression of rol-3 lethality, and that rol-3 may act in some
      way to influence proper posterior morphogenesis. Finally, based on our genetic
      analysis of rol-3 and the srl mutations, we present a model whereby the wild-type
      products of the srl loci act in a concerted manner to negatively regulate the rol
      3 gene.

PMID- 8138152
TI  - Isolation, characterization and epistasis of fluoride-resistant mutants of
      Caenorhabditis elegans.
AB  - We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis
      elegans. All the mutations are recessive and mapped to five genes. Mutants in
      three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant
      to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have
      smaller brood size than wild-type worms even in the absence of fluoride ion. In
      contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are
      only partially resistant to 400 micrograms/ml NaF, and they have almost normal
      growth rates and brood sizes in the absence of fluoride ion. Studies on the
      phenotypes of double mutants showed that class 2 mutations are epistatic to class
      1 mutations concerning growth rate and brood size but hypostatic with respect to
      fluoride resistance. We propose two models that can explain the epistasis. Since
      fluoride ion depletes calcium ion, inhibits some protein phosphatases and
      activates trimeric G-proteins, studies on these mutants may lead to discovery of
      a new signal transduction system that controls the growth of C. elegans.

PMID- 8138153
TI  - Evolutionary inferences from DNA variation at the 6-phosphogluconate
      dehydrogenase locus in natural populations of drosophila: selection and
      geographic differentiation.
AB  - Several allozyme-coding genes in Drosophila melanogaster show patterns suggesting
      that polymorphisms at these loci are targets of balancing selection. An important
      question is whether these genes have similar distributions of underlying DNA
      sequence variation which would indicate similar evolutionary processes occurring
      in this class of loci. One such locus, 6-phosphogluconate dehydrogenase (Pgd),
      has previously been shown to exhibit clinal variation for Fast/Slow electromorph
      variation in the United States and Australia, unusually large electromorph
      frequency differences between the United States and Africa, and other patterns
      indicative of selection. We measured four-cutter DNA restriction site and
      allozyme variation at Pgd among 142 D. melanogaster X chromosomes collected from
      several geographic regions including North Carolina, California, and Zimbabwe
      (Africa). We also sequenced a representative sample of 13 D. melanogaster Pgd
      genes collected in North Carolina and a single copy of Pgd from the sibling
      species, Drosophila simulans. While some population genetic models predict excess
      DNA polymorphism in genes which are targets of balancing selection, the D.
      melanogaster samples from the United States had significantly reduced levels of
      DNA polymorphism and extraordinarily high levels of linkage disequilibrium,
      providing evidence of hitchhiking effects of advantageous mutants at Pgd or at
      linked sites. Therefore, while selection has probably influenced the distribution
      of DNA variation at Pgd, the precise nature of these selective events remains
      obscure. Since the Pgd region appears to have low rates of crossing over, the
      reduced level of variation at this locus supports the idea that recombination
      rates are important determinants of levels of DNA polymorphism in natural
      populations. Furthermore, while patterns of allozyme variation are very similar
      at Pgd and Adh, the DNA data show that the evolutionary histories of these genes
      are dramatically different. We observed extensive differences in the amount and
      distribution of variation in D. melanogaster Pgd samples from the United States
      and Zimbabwe which cannot be explained by differential selection on the Fast/Slow
      polymorphism in these two geographic regions. Thus, genetic drift among partially
      isolated populations has also been an important factor in determining the
      distribution of variation at Pgd in D. melanogaster. Finally, we assayed four
      cutter variation at Pgd in a sample of 19 D. simulans X chromosomes and observed
      reduced levels of DNA variability and high levels of linkage disequilibrium.
      These patterns are consistent with predictions of some hitchhiking models.

PMID- 8138154
TI  - Structure of recombinants from conjugational crosses between Escherichia coli
      donor and mismatch-repair deficient Salmonella typhimurium recipients.
AB  - To get more insight into the control of homologous recombination between diverged
      DNA by the Mut proteins of the long-patch mismatch repair system, we have studied
      interspecies Escherichia coli/Salmonella typhimurium recombination. Knowing that
      the same recombination pathway (RecABCD) is responsible for intraspecies and
      interspecies recombination, we have now studied the structure (replacement vs.
      addition-type or other rearrangement-type recombinants) of 81 interspecies
      recombinants obtained in conjugational crosses between E. coli donor and mutL,
      mutS, mutH, mutU or mut+ S. typhimurium recipients. Taking advantage of high
      interspecies sequence divergence, a physical analysis was performed on one third
      of the E. coli Hfr genome, which was expected to be transferred to S. typhimurium
      F- recipients during 40 min before interruption of the mating. Probes specific
      for each species were hybridized on dot blots of genomic DNA, or on colonies, and
      the composition of the rrn operons was determined from purified genomic DNA. With
      very few exceptions, the structure of these interspecies recombinants corresponds
      to replacements of one continuous block of the recipient genome by the
      corresponding region of the donor genome.

PMID- 8138155
TI  - forked proteins are components of fiber bundles present in developing bristles of
      Drosophila melanogaster.
AB  - The forked (f) gene of Drosophila melanogaster encodes six different transcripts
      6.4, 5.6, 5.4, 2.5, 1.9, and 1.1 kb long. These transcripts arise by the use of
      alternative promoters. A polyclonal antibody raised against a domain common to
      all of the forked-encoded products has been used to identify forked proteins on
      two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels
      and in Drosophila pupal tissues. The antibody stains fiber bundles present in
      bristle cells for about 15 hr during normal pupal development. Electron
      microscopy shows that these fibers are present from 40 to 53 hr in bristles of
      wild-type flies but are absent in the null f36a mutant. The forked protein(s)
      thus appear to be an essential part of the bristle fibers. The phenotype of the
      f36a mutation can be rescued by a 13-kb fragment of the forked locus containing
      the coding regions for the 2.5, 1.9, and 1.1-kb transcripts, suggesting that the
      proteins encoded by the three large forked RNAs are dispensable during bristle
      development. Increasing the copy number of a P[w+,f+] construct containing the 13
      kb fragment induces a hypermorphic bristle phenotype whose severity correlates
      with the number of copies of P[w+,f+] present. These results indicate that
      alterations in the ratios among the forked proteins, or between forked products
      and other components of the fiber, result in abnormal assembly of the fibrillar
      cytoplasmic structures necessary for bristle morphogenesis.

PMID- 8138156
TI  - Modifications of the notch function by Abruptex mutations in Drosophila
      melanogaster.
AB  - The function of the Notch gene is required in cell interactions defining
      alternative cell fates in several developmental processes. The Notch gene encodes
      a transmembrane protein with 36 epidermal growth factor (EGF)-like repeats in its
      extracellular domain. This protein functions as a receptor that interacts with
      other transmembrane proteins, such as Serrate and Delta, which also have EGF
      repeats in their extracellular domain. The Abruptex mutations of the Notch locus
      are associated with amino acid substitutions in the EGF repeats 24-29 of the
      Notch protein. We have studied, in genetic combinations, the modifications of
      Notch function caused by Abruptex mutations. These mutations lead to phenotypes
      which are opposite to those caused by Notch deletions. The Abruptex phenotypes
      are modified by the presence of mutations in other loci, in particular in the
      genes Serrate and Delta as well as Hairless, and groucho. The results suggest
      that all Abruptex mutations cause stronger than normal Notch activation by the
      Delta protein. Some Abruptex alleles also display an insufficiency of N function.
      Abruptex alleles which produce stronger enhancement of Notch activation also
      display stronger Notch insufficiency. This insufficiency could be due to reduced
      ability of Abruptex proteins to interact with Notch ligands and/or to form
      functional Notch dimers.

PMID- 8138157
TI  - A genetic analysis of hermaphrodite, a pleiotropic sex determination gene in
      Drosophila melanogaster.
AB  - Sex determination in Drosophila is controlled by a cascade of regulatory genes.
      Here we describe hermaphrodite (her), a new component of this regulatory cascade
      with pleiotropic zygotic and maternal functions. Zygotically, her+ function is
      required for female sexual differentiation: when zygotic her+ function is
      lacking, females are transformed to intersexes. Zygotic her+ function may also
      play a role in male sexual differentiation. Maternally, her+ function is needed
      to ensure the viability of female progeny: a partial loss of her+ function
      preferentially kills daughters. In addition, her has both zygotic and maternal
      functions required for viability in both sexes. Temperature sensitivity prevails
      for all known her alleles and for all of the her phenotypes described above,
      suggesting that her may participate in an intrinsically temperature-sensitive
      process. This analysis of four her alleles also indicates that the zygotic and
      maternal components of of her function are differentially mutable. We have
      localized her cytologically to 36A3-36A11.

PMID- 8138158
TI  - Characterization of two Segregation distorter revertants: evidence that the
      tandem duplication is necessary for Sd activity in Drosophila melanogaster.
AB  - Segregation Distorter (SD) is a naturally occurring system of meiotic drive in
      Drosophila melanogaster. Males heterozygous for an SD second chromosome and a
      normal homolog (SD+) transmit predominantly SD-bearing sperm. To accomplish this,
      the Segregation distorter (Sd) locus induces the dysfunction of those spermatids
      that receive the SD+ chromosome. Recently, P. A. Powers and B. Ganetzky isolated
      overlapping DNA clones spanning the region of DNA known to contain the Sd gene
      and identified a 5-kb tandem duplication that is present on all SD chromosomes
      examined, but is apparently absent from wild-type chromosomes. Here we report a
      molecular analysis of two spontaneous revertants from an Australian SD chromosome
      (SD-Arm28). Both of these revertants have lost the 5-kb tandem duplication along
      with the ability to distort transmission; the critical observation, however, is
      that they retain the DNA haplotype in the flanking regions (both proximally and
      distally) that is characteristic of the original SD-Arm28. We propose unequal
      sister chromatid exchange between the tandem repeats as the only plausible
      explanation for loss of a repeat while retaining flanking markers. This provides
      direct evidence that the tandem duplication is indeed necessary for the Sd
      phenotype. Further, we examined testes-specific levels of both RNA and protein
      for the nearby Topoisomerase 2 gene. Neither revealed a consistent difference
      between SD and SD+ strains. We also measured testes-specific levels of RNA using
      the tandem duplication itself as probe. Our results suggest that there is strong
      up-regulation of one or several 2.0-2.3-kb transcripts from the duplicated region
      in the testes of an SD strain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138159
TI  - Fine structure mapping and deletion analysis of the murine piebald locus.
AB  - piebald (s) is a recessive mutation that affects the development of two cell
      types of neural crest origin: the melanocytes, responsible for pigment synthesis
      in the skin, and enteric ganglia, which innervate the lower bowel. As a result,
      mice carrying piebald mutations exhibit white spotting in the coat and
      aganglionic megacolon. Previously the gene had been localized to the distal half
      of mouse chromosome 14. To determine its precise location relative to molecular
      markers, an intersubspecific backcross was generated. Two anchor loci of
      chromosome 14, slaty and hypogonadal, in addition to simple sequence length
      repeat markers, were used to localize s to a 2-cM interval defined by the markers
      D14Mit38 and D14Mit42. The molecular markers were also used to characterize nine
      induced s alleles. Three of these mutations exhibited no deletions or
      rearrangements of the flanking markers, whereas the other six had two or more of
      these markers deleted. The extent of the deletions was found to be consistent
      with the severity of the homozygous phenotype. The location of deletion
      breakpoints in the induced alleles, coupled with the recombination breakpoints in
      the backcross progeny, provide useful molecular landmarks to define the location
      of the piebald gene.

PMID- 8138160
TI  - Co-segregation of intermale aggression with the pseudoautosomal region of the Y
      chromosome in mice.
AB  - The sexual dimorphism of aggression has led to a search for its Y chromosomal
      correlates. We have previously confirmed that initiation of attack behavior
      against a conspecific male is Y-dependent in two strains of laboratory mice (NZB
      and CBA/H). We provide evidence that the non-pseudoautosomal region of the Y is
      not involved and that only the pseudoautosomal region of the Y is correlated with
      initiation of attack behavior. The autosomal correlates also contribute to this
      behavior in an additive or interactive manner with the pseudoautosomal
      correlates.

PMID- 8138161
TI  - A microsatellite linkage map of the porcine genome.
AB  - We report the most extensive genetic linkage map for a livestock species produced
      to date. We have linked 376 microsatellite (MS) loci with seven restriction
      fragment length polymorphic loci in a backcross reference population. The 383
      markers were placed into 24 linkage groups which span 1997 cM. Seven additional
      MS did not fall into a linkage group. Linkage groups are assigned to 13 autosomes
      and the X chromosome (haploid n = 19). This map provides the basis for genetic
      analysis of quantitative inheritance of phenotypic and physiologic traits in
      swine.

PMID- 8138162
TI  - The peculiar evolution of apolipoprotein(a) in human and rhesus macaque.
AB  - Apo(a) is a low density lipoprotein homologous to plasminogen and has been shown
      to be involved in coronary atherosclerosis. In the present paper we will try to
      analyze the interesting evolutionary pattern of Apo(a). The plasminogen gene
      contains 5 cysteine-rich sequences, called kringles, followed by a protease
      domain. Apo(a), probably arisen by duplication of an ancestral plasminogen gene,
      contains many tandemly repeated copies of a sequence domain similar to the fourth
      kringle of plasminogen, 37 in human and at least 10 in the partially sequenced
      gene of rhesus, and the protease domain. We have found that the upstream kringles
      of apo(a) undergo Molecular Drive-like processes that produce high intraspecies
      similarity, whereas the downstream kringles evolve in a molecular clock-like
      manner and show an high interspecies sequence similarity. The latter regions are
      obviously suitable for dating the duplication event by which Apo(a) arose from
      plasminogen, but only if they evolve at the same rate in the two genes. Thus, we
      propose a "Molecular Clock Test" for assessing whether the comparison of two
      paralogous genes (or gene regions) can give reliable information on the dating of
      their origin by duplication. Applying this test to the kringle-4 domain of apo(a)
      and plasminogen gene, we demonstrate that the separation between the two genes by
      duplication dates back at about 90 Mya immediately before the radiation of
      mammals.

PMID- 8138163
TI  - Distribution of unlinked receptor sites for transposed Ac elements from the bz
      m2(Ac) allele in maize.
AB  - We have shown before that the Ac element from the maize bz-m2(Ac) allele, located
      in the short arm of chromosome 9 (9S), transposes preferentially to sites that
      are linked to the bz donor locus. Yet, about half of the Ac transpositions
      recovered from bz-m2(Ac) are in receptor sites not linked to the donor locus. In
      this study, we have analyzed the distribution of those unlinked receptor sites.
      Thirty-seven transposed Ac (trAc) elements that recombined independently of the
      bz locus were mapped using a set of wx reciprocal translocations. We found that
      the distribution of unlinked receptor sites for trAs was not random. Ten trAcs
      mapped to 9L, i.e., Ac had transposed to sites physically, if not genetically,
      linked to the donor site. Among chromosomes other than 9, the Ac element of bz
      m2(Ac) appeared to have transposed preferentially to certain chromosomes, such as
      5 and 7, but infrequently to others, such as 1, the longest chromosome in the
      maize genome. The seven trAc elements in chromosome 5 were mapped relative to
      markers in 5S and 5L and localized to both arms of 5. We also investigated the
      transposition of Ac to the homolog of the donor chromosome. We found that Ac
      rarely transposes from bz-m2(Ac) to the homologous chromosome 9. The clustering
      of Ac receptor sites around the donor locus has been taken to mean that a
      physical association between the donor site and nearby receptor sites occurs
      during transposition. The preferential occurrence of 9L among chromosomes
      harboring unlinked receptor sites would be expected according to this model,
      since sites in 9L would tend to be physically closer to 9S than sites in other
      chromosomes. The nonrandom pattern seen among the remaining chromosomes could
      reflect an underlying nuclear architecture, i.e., an ordering of the chromosomes
      in the interphase nucleus, as suggested from previous cytological observations.

PMID- 8138164
TI  - Approaches to half-tetrad analysis in bacteria: recombination between repeated,
      inverse-order chromosomal sequences.
AB  - In standard bacterial recombination assays, a linear fragment of DNA is
      transferred to a recipient cell and, at most, a single selected recombinant type
      is recovered from each merozygote. This contrasts with fungal systems, for which
      tetrads allow recovery of all meiotic products, including both ultimate
      recombinant products of an apparent single act of recombination. We have
      developed a bacterial recombination system in which two recombining sequences are
      placed in inverse order at widely separated sites in the circular chromosome of
      Salmonella typhimurium. Recombination can reassort markers between these repeated
      sequences (double recombination and apparent gene conversion), or can exchange
      flanking sequences, leading to inversion of the chromosome segment between the
      recombining sequences. Since two recombinant products remain in the chromosome of
      a recombinant with an inversion, one can, in principle, approach the capability
      of tetrad analysis. Using this system, the following observations have been made.
      (a) When long sequences (40 kb) recombine, conversion frequently accompanies
      exchange of flanking sequences. (b) When short sequences (5 kb) recombine,
      conversion rarely accompanies exchange of flanks. (c) Both recA and recB
      mutations eliminate inversion formation. (d) The frequency of exchanges between
      short repeats is more sensitive to the distance separating the recombining
      sequences in the chromosome. The results are presented with the assumption that
      inversions occur by simple interaction of two sequences in the same circular
      chromosome. In an appendix we discuss mechanistically more complex possibilities,
      some of which could also apply to standard fungal systems.

PMID- 8138165
TI  - Genetic analysis of 63 mutations affecting maize kernel development isolated from
      Mutator stocks.
AB  - Sixty-three mutations affecting development of the maize kernel were isolated
      from active Robertson's Mutator (Mu) stocks. At least 14 previously undescribed
      maize gene loci were defined by mutations in this collection. Genetic mapping
      located 53 of these defective kernel (dek) mutations to particular chromosome
      arms, and more precise map determinations were made for 21 of the mutations.
      Genetic analyses identified 20 instances of allelism between one of the novel
      mutations and a previously described dek mutation, or between new dek mutations
      identified in this study; phenotypic variability was observed in three of the
      allelic series. Viability testing of homozygous mutant kernels identified
      numerous dek mutations with various pleiotropic effects on seedling and plant
      development. The mutations described here presumably arose by insertion of a Mu
      transposon within a dek gene; thus, many of the affected loci are expected to be
      accessible to molecular cloning via transposon-tagging.

PMID- 8138166
TI  - Genetic analysis of Rough sheath1 developmental mutants of maize.
AB  - Maize Rough sheath1 (Rs1) mutants are dominant and cause a proliferation of
      sheath-like tissue at the base of the blade and throughout the ligular region.
      They also cause ligule displacement, a chaotic pattern of vasculature and
      abnormal cellular structure of vascular bundles. The affected region of Rs1-O
      leaves displays genetic and morphological attributes of both sheath and auricle,
      suggesting an overlap of these genetic programs. The rs1 locus maps approximately
      26 map units distal to opaque2 (o2) on chromosome 7S, defining a new distal-most
      locus on the genetic map. Three mutant alleles, Rs1-O, Rs1-1025 and Rs1-Z, all
      display similar phenotypes. The mutations are completely dominant and the Rs1-O
      phenotype is not affected by dosage of the chromosome arm carrying the rs1+
      allele, indicating that these alleles are neomorphic. Analysis of genetic mosaics
      showed that the Rs1-O phenotype is non-cell-autonomous, suggesting that
      intercellular signals convey the phenotype. Rs1 mutant phenotypes are affected by
      modifiers present in particular genetic backgrounds. An enhancer of Rs1-O was
      identified; segregation data imply a single recessive gene, ers1. Rs1 mutants
      were also found to enhance the expression of unlinked rs2 and Rs4 mutants,
      suggesting that these mutations affect similar developmental processes. We
      discuss the phenotypic and genetic similarities between Rs1 and Knotted 1 (Kn1)
      mutants that led to the identification of rs1 as a kn1-like homeobox gene
      (unpublished data).

PMID- 8138167
TI  - Genetic analysis of male reproductive contributions in Chamaelirium luteum (L.)
      gray (Liliaceae).
AB  - Genealogical analysis is a powerful tool for analysis of reproductive performance
      in both natural and captive populations, but assignment of paternity has always
      been a stumbling block for this sort of work. Statistical methods for determining
      paternity have undergone several phases of development, ranging from
      straightforward genetic exclusion to assignment of paternity based on genetic
      likelihood criteria. In the present study, we present a genetic likelihood-based
      iterative procedure for fractional allocation of paternity within a progeny pool
      and apply this method to a population of Chamaelirium luteum, a dioecious member
      of the Liliaceae. Results from this analysis clearly demonstrate that different
      males make unequal contributions to the overall progeny pool, with many males
      contributing essentially nothing to the next generation. Furthermore, the
      distribution of paternal success among males shows a highly significant departure
      from (Poisson) randomness. The results from the present analysis were compared
      with earlier results obtained from the same data set, using likelihood-based
      categorical paternity assignments. The general biological pattern revealed by the
      two analyses is the same, but the estimates of reproductive success are only
      modestly (though significantly) correlated. The iterative procedure makes more
      complete use of the data and generates a more sharply resolved distribution of
      male reproductive success.

PMID- 8138168
TI  - Evidence for the partial dominance of viability genes contributing to inbreeding
      depression in Mimulus guttatus.
AB  - The relative importance of different modes of gene expression of viability genes
      contributing to inbreeding depression was investigated in the wild plant, Mimulus
      guttatus. Viability genes were identified by self-fertilizing 31 outbred plants,
      each heterozygous for three to nine unlinked allozyme markers, and analyzing
      segregation ratios of selfed progeny at maturity for deviations from 1:2:1
      ratios. In this study, 24 linkages of viability genes to marker loci were
      detected. To infer the nature of gene action for these viability genes, a "model
      free" graphical method was developed that examines the "space" of segregation
      ratios allowed by each of seven selection models (i.e., overdominance, complete
      recessivity, partial recessivity, additivity, partial dominance, complete
      dominance and underdominance). Using this method, we found that, of 24 linkages
      detected, 18 were consistent with either partial dominance, complete dominance or
      underdominance. Six were consistent with either partial recessivity, complete
      recessivity or overdominance. This finding indicates that, in these chromosomal
      segments identified by allozyme markers, partial dominance plays the predominant
      role in inbreeding depression. This is inconsistent with either the dominance or
      overdominance hypotheses proposed to account for inbreeding depression.

PMID- 8138169
TI  - Possible role of natural selection in the formation of tandem-repetitive
      noncoding DNA.
AB  - A simulation model of sequence-dependent amplification, unequal crossing over and
      mutation is analyzed. This model predicts the spontaneous formation of tandem
      repetitive patterns of noncoding DNA from arbitrary sequences for a wide range of
      parameter values. Natural selection is found to play an essential role in this
      self-organizing process. Natural selection which is modeled as a mechanism for
      controlling the length of a nucleotide string but not the sequence itself favors
      the formation of tandem-repetitive structures. Two measures of sequence
      heterogeneity, inter-repeat variability and repeat length, are analyzed in
      detail. For fixed mutation rate, both inter-repeat variability and repeat length
      are found to increase with decreasing rates of (unequal) crossing over. The
      results are compared with data on micro-, mini- and satellite DNAs. The
      properties of minisatellites and satellite DNAs resemble the simulated structures
      very closely. This suggests that unequal crossing over is a dominant long-range
      ordering force which keeps these arrays homogeneous even in regions of very low
      recombination rates, such as at satellite DNA loci. Our analysis also indicates
      that in regions of low rates of (unequal) crossing over, inter-repeat variability
      is maintained at a low level at the expense of much larger repeat units
      (multimeric repeats), which are characteristic of satellite DNA. In contrast, the
      microsatellite data do not fit the proposed model well, suggesting that unequal
      crossing over does not act on these very short tandem arrays.

PMID- 8138170
TI  - Using allele frequencies and geographic subdivision to reconstruct gene trees
      within a species: molecular variance parsimony.
AB  - We formalize the use of allele frequency and geographic information for the
      construction of gene trees at the intraspecific level and extend the concept of
      evolutionary parsimony to molecular variance parsimony. The central principle is
      to consider a particular gene tree as a variable to be optimized in the
      estimation of a given population statistic. We propose three population
      statistics that are related to variance components and that are explicit
      functions of phylogenetic information. The methodology is applied in the context
      of minimum spanning trees (MSTs) and human mitochondrial DNA restriction data,
      but could be extended to accommodate other tree-making procedures, as well as
      other data types. We pursue optimal trees by heuristic optimization over a search
      space of more than 1.29 billion MSTs. This very large number of equally
      parsimonious trees underlines the lack of resolution of conventional parsimony
      procedures. This lack of resolution is highlighted by the observation that
      equally parsimonious trees yield very different estimates of population genetic
      diversity and genetic structure, as shown by null distributions of the population
      statistics, obtained by evaluation of 10,000 random MSTs. We propose a non
      parametric test for the similarity between any two trees, based on the
      distribution of a weighted coevolutionary correlation. The ability to test for
      tree relatedness leads to the definition of a class of solutions instead of a
      single solution. Members of the class share virtually all of the critical
      internal structure of the tree but differ in the placement of singleton branch
      tips.

PMID- 8138171
TI  - Geographical variation in a quantitative character.
AB  - A model for the evolution of the local averages of a quantitative character under
      migration, selection, and random genetic drift in a subdivided population is
      formulated and investigated. Generations are discrete and nonoverlapping; the
      monoecious, diploid population mates at random in each deme. All three
      evolutionary forces are weak, but the migration pattern and the local population
      numbers are otherwise arbitrary. The character is determined by purely additive
      gene action and a stochastically independent environment; its distribution is
      Gaussian with a constant variance; and it is under Gaussian stabilizing selection
      with the same parameters in every deme. Linkage disequilibrium is neglected. Most
      of the results concern the covariances of the local averages. For a finite number
      of demes, explicit formulas are derived for (i) the asymptotic rate and pattern
      of convergence to equilibrium, (ii) the variance of a suitably weighted average
      of the local averages, and (iii) the equilibrium covariances when selection and
      random drift are much weaker than migration. Essentially complete analyses of
      equilibrium and convergence are presented for random outbreeding and site homing,
      the Levene and island models, the circular habitat and the unbounded linear
      stepping-stone model in the diffusion approximation, and the exact unbounded
      stepping-stone model in one and two dimensions.

PMID- 8138172
TI  - The use of mixture models to detect effects of major genes on quantitative
      characters in a plant breeding experiment.
AB  - An analysis based on Elston's model of mixed major locus and polygenic
      inheritance is extended to include populations of progeny testing such as F3, B1s
      and B2s families derived from F2 and backcrosses in a cross between two inbred
      lines. Genetic hypotheses that can be validly tested by the likelihood ratio
      method in the analysis of a breeding experiment include homogeneity of variances
      due to environment and/or polygenes with transformable scale effect by Box-Cox
      power function, random and independent segregation of major genes, invariance of
      the effects of major genes with population types and additive and dominant models
      for polygenes. Testing hypotheses in the order suggested here can lead to a
      gradual simplification of the models and increases the feasibility of the
      subsequent analysis, but caution must be paid to the possible bias in parameter
      estimation and hypotheses tests. The procedure is applied to a set of data on
      plant height of rice with the effects of dwarf genes in crosses among three
      varieties. Two recessive dwarf genes are shown to be nonallelic and unlinked. One
      dwarf gene is shown to reduce plant height about 36-56 cm, and another 52-61 cm.
      The effect of polygenes, estimated as the standard deviation among possible
      inbred lines derived from these crosses, is about 11.7 cm. Interactions between
      the dwarf genes and the polygenic background are found, especially for one of the
      two genes. Both the polygenic effects and the interactions are much smaller than
      the effects of the major dwarf genes.

PMID- 8138173
TI  - The evolution of dimorphic traits: predicting the genetic correlation between
      environments.
AB  - Many traits vary in a dichotomous manner, although the underlying genetic
      determination is polygenic. The genetic basis of such dimorphic traits can be
      analyzed using the threshold model, in which it is assumed that there is a
      continuously distributed underlying character and the phenotype is determined by
      whether the character is above or below a threshold. Threshold traits frequently
      vary with environmental variables such as photoperiod, temperature and density.
      This effect can be accounted for using a threshold model in which (1) there is a
      critical value of the environmental variable at which a genotype switches to the
      alternate morph, and (2) switch (threshold) points are normally distributed in
      the population. I term this the environmental threshold (ET) model. I show that
      the ET model predicts that across environments differing in only one factor the
      genetic correlation will be 1. This prediction is supported by data from three
      wing dimorphic insects. Evidence is presented that the genetic correlation
      between environments differing in two components (temperature and photoperiod) is
      less than 1.

PMID- 8138174
TI  - Statistical approaches for analyzing mutational spectra: some recommendations for
      categorical data.
AB  - In studies examining the patterns or spectra of mutational damage, the primary
      variables of interest are expressed typically as discrete counts within defined
      categories of damage. Various statistical methods can be applied to test for
      heterogeneity among the observed spectra of different classes, treatment groups
      and/or doses of a mutagen. These are described and compared via computer
      simulations to determine which are most appropriate for practical use in the
      evaluation of spectral data. Our results suggest that selected, simple
      modifications of the usual Pearson X2 statistic for contingency tables provide
      stable false positive error rates near the usual alpha = 0.05 level and also
      acceptable sensitivity to detect differences among spectra. Extensions to the
      problem of identifying individual differences within and among mutant spectra are
      noted.

PMID- 8138175
TI  - Drosophila genetics in the classroom.
AB  - Drosophila has long been useful for demonstrating the principles of classical
      Mendelian genetics in the classroom. In recent years, the organism has also
      helped students understand biochemical and behavioral genetics. In this
      connection, this article describes the development of a set of integrated
      laboratory exercises and descriptive materials--a laboratory module--in
      biochemical genetics for use by high-school students. The module focuses on the
      Adh gene and its product, the alcohol dehydrogenase enzyme. Among other
      activities, students using the module get to measure alcohol tolerance and to
      assay alcohol dehydrogenase activity in Adh-negative and -positive flies. To
      effectively present the module in the classroom, teachers attend a month-long
      Dissemination Institute in the summer. During this period, they learn about other
      research activities that can be adapted for classroom use. One such activity that
      has proved popular with teachers and students utilizes Drosophila to introduce
      some of the concepts of behavioral genetics to the high-school student. By
      establishing closer interactions between high-school educators and research
      scientists, the gulf between the two communities can begin to be bridged. It is
      anticipated that the result of a closer relationship will be that the excitement
      and creativity of science will be more effectively conveyed to students.

PMID- 8138176
TI  - Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the silent
      mating-type loci in fission yeast.
AB  - In Schizosaccharomyces pombe the mating-type information is stored at two
      transcriptionally silent loci (mat2 and mat3). The region between these sites (K
      region) is inert for meiotic crossing over. The mating-type genes (M or P) are
      expressed only when present at a third, active locus (mat1). We have earlier
      shown that the positional regulation of P genes is based on repression at the
      silent site, caused by elements in the flanking DNA sequences. In this study we
      have mutagenized a sterile mat1 deleted strain and selected for cells that are
      able to conjugate. Recessive mutations of this type should define genes encoding
      trans-acting factors involved in repression of the silent mating-type loci.
      Before this work mutations in two genes, clr1 and swi6, had been shown to allow
      both expression of the silent loci and recombination in the K region. The
      sensitivity of the present selection is demonstrated by the isolation of new
      mutations that derepress one or both of the silent loci (M-mating or bi-mating).
      The frequency of M-mating mutants was almost two orders of magnitude higher than
      that of bi-mating mutants and in all mutants analyzed mat3-M expression was
      significantly higher than mat2-P expression. The mutations define three new
      genes, clr2, clr3 and clr4. In addition we show that the rik1 mutant previously
      known to allow recombination in the K region also depresses the silent loci.

PMID- 8138177
TI  - The yeast med1 mutant undergoes both meiotic homolog nondisjunction and
      precocious separation of sister chromatids.
AB  - A mutant at the yeast MED1 locus was isolated in a screen for sporulation
      proficient, meiotic-lethal mutants. Synaptonemal complex formation in the med1
      mutant is apparently normal and med1 strains undergo meiotic crossing over at
      approximately 50% of the wild-type level. The med1 mutant undergoes homolog
      nondisjunction at meiosis I, presumably as a consequence of the decrease in
      crossing over. In addition, the mutant undergoes precocious separation of sister
      chromatids, resulting in chromosome missegregation at both meiotic divisions. We
      suggest that the med1 mutation perturbs chromosome structure, leading to a
      reduction in recombination and a defect in sister chromatid cohesion.

PMID- 8138178
TI  - Translational maintenance of frame: mutants of Saccharomyces cerevisiae with
      altered -1 ribosomal frameshifting efficiencies.
AB  - A special site on the (+) strand of the L-A dsRNA virus induces about 2% of
      ribosomes translating the gag open reading frame to execute a -1 frameshift and
      thus produce the viral gag-pol fusion protein. Using constructs in which a -1
      ribosomal frameshift at this site was necessary for expression of lacZ we
      isolated chromosomal mutants in which the efficiency of frameshifting was
      increased. These mutants comprise eight genes, named mof (maintenance of frame).
      The mof1-1, mof2-1, mof4-1, mof5-1 and mof6-1 strains cannot maintain M1 dsRNA at
      30 degrees, but, paradoxically, do not lose L-A. The mof2-1, mof5-1 and mof6-1
      strains are temperature sensitive for growth at 37 degrees, and all three show
      striking cell cycle phenotypes. The mof2-1 strains arrest with mother and
      daughter cells almost equal in size, mof5-1 arrests with multiple buds and mof6-1
      arrests as single large unbudded cells. mof2-1 and mof5-1 strains are also Pet-.
      The mof mutations show differential effects on various frameshifting signals.

PMID- 8138179
TI  - Formamide sensitivity: a novel conditional phenotype in yeast.
AB  - Yeast mutants unable to grow in the presence of 3% formamide have been isolated
      in parallel with mutants sensitive to either 37 degrees or 6% ethanol. The number
      of formamide-sensitive mutations that affect different genes that can be
      identified from yeast cells is at least as large as the number of thermosensitive
      or ethanol-sensitive mutations. These mutations are of two types: those that are
      sensitive to formamide, temperature and/or ethanol simultaneously; and those that
      are specific for formamide sensitivity and show no temperature or ethanol
      sensitivity phenotype. Those genes susceptible to giving rise to formamide
      sensitive alleles include the structural gene for DNA ligase, CDC9, and the
      structural gene for arginine permease, CAN1. The results indicate that formamide
      sensitivity can be used as a novel conditional phenotype for mutations on both
      essential and nonessential genes. This work also confirms that ethanol
      sensitivity can be used as a conditional phenotype to identify mutations in at
      least as many genes as those susceptible to temperature or formamide sensitive
      mutations.

PMID- 8138180
TI  - The SPT10 and SPT21 genes of Saccharomyces cerevisiae.
AB  - Mutations in the SPT10 and SPT21 genes were originally isolated as suppressors of
      Ty and LTR (delta) insertion mutations in Saccharomyces cerevisiae, and the genes
      were shown to be required for normal transcription at a number of loci in yeast.
      Now we have cloned, sequenced, mapped and mutagenized SPT10 and SPT21. Since the
      spt10 mutation used to clone SPT10 resulted in very poor transformation
      efficiency, a novel method making use of the kar1-1 mutation was used. Neither
      SPT gene is essential for growth, and constructed null alleles cause phenotypes
      similar to those caused by spontaneous mutations in the genes. spt10 null alleles
      are strong suppressor mutations and cause extremely slow growth. Certain spt10
      spontaneous alleles are good suppressors but have a normal growth rate,
      suggesting that the SPT10 protein may have two distinct functions. An amino acid
      sequence motif that is similar to the Zn-finger motif was found in SPT10.
      Mutation of the second Cys residue in this motif resulted in loss of
      complementation of the suppression phenotype but a normal growth rate. Thus, this
      motif may reside in a part of the SPT10 protein that is important for
      transcriptional regulation but not for normal growth. Both the SPT10 and SPT21
      proteins are relatively tolerant of large deletions; in both cases deletions of
      the C-terminus resulted in at least partially functional proteins; also, a large
      internal deletion in SPT21 was phenotypically wild type.

PMID- 8138181
TI  - Simultaneous determination of Fe(III) and Fe(II) in water solutions and tissue
      homogenates using desferal and 1,10-phenanthroline.
AB  - At neutral pH values 1,10-phenanthroline forms a colored complex with Fe(II), but
      it does not form such a complex with Fe(III). On the contrary, only Fe(III) forms
      with desferal a yellow complex with a g = 4.3 electron paramagnetic resonance
      (EPR) signal, but Fe(II) is rapidly oxidized by desferal to Fe(III), which gives
      then a yellow complex. On the basis of these facts, a method for simultaneous
      determination of both Fe(II) and Fe(III) ions was elaborated using a desferal
      phenanthroline mixture. Two ways of detecting Fe(II) and Fe(III) have been
      suggested: (1) the spectrophotometric method for transparent water solutions, and
      (2) the EPR-spectrometric method for turbid solutions and tissue homogenates. The
      latter method was applied for determination of free and weakly bound iron in rat
      liver. The Fe(II) amount in intact liver was 22.2 +/- 7.6 nmol/g of wet tissue;
      free Fe(III) was not found.

PMID- 8138182
TI  - Chemiluminescent response to PMA in isolated rat liver after in situ ischemia
      reperfusion.
AB  - The median and left lateral lobes of rat liver in situ were rendered ischemic for
      30 min, then blood flow reinstituted. After 1, 3, 6, 24, or 48 h, livers were
      removed and set up for isolated perfused organ study. Luminol enhanced
      chemiluminescence (LEC) was recorded from the surface of the median and left
      lateral lobes before and for 90 min following phorbol myristate acetate (PMA, 1.6
      x 10(-8) M) perfusion. An increase in PMA induced LEC was evident at 1 h and
      continued to increase up to 6 h. By 24 h the magnitude of the PMA response had
      returned to within control values. This indicates that a large influx of
      inflammatory cells had occurred in the liver following the in vivo ischemia
      reperfusion insult and that these cells were well fixed in the tissue and capable
      of mounting a very large and sustained burst of radical production on stimulation
      with PMA. This combined in vivo/in vitro technique is ideally suited for the
      assessment of interventions designed to ameliorate damage following oxidative
      stress.

PMID- 8138183
TI  - Expression of human catalase in acatalasemic murine SV-B2 cells confers
      protection from oxidative damage.
AB  - Reactive oxygen species have been implicated in aerobic organisms as causative
      agents in damage to DNA, proteins, and lipids. Catalase is a major enzyme in the
      defense against such oxidant damage. To determine whether increased catalase
      expression confers greater resistance to oxidant stress, a eukaryotic expression
      vector harboring a human catalase cDNA clone was constructed. Acatalasemic murine
      fibroblasts were then co-transfected with that catalase expression vector and
      pSV2-neo, and successfully transfected cells were identified by their ability to
      grow in the presence of geneticin. Clones that contained integrated copies of the
      catalase expression vector were identified by Polymerase Chain Reaction (PCR)
      analysis. Stably transfected geneticin-resistant cell lines that overexpressed
      catalase in potentially positive cell lines were confirmed by catalase enzyme
      assays. To examine the physiological relevance of catalase overexpression, cells
      were exposed to oxidant stresses (hydrogen peroxide and hyperoxia), and survival
      rates were determined. Results demonstrated a significant resistance to oxidative
      stress in cells overexpressing catalase when compared to controls. These
      transfected cell lines will provide important models for further evaluation of
      the role of catalase in protecting cells against the toxic effects of oxygen
      derived free radicals and their derivatives.

PMID- 8138184
TI  - An electron paramagnetic resonance study of the antioxidant properties of the
      nitroxide free radical TEMPO.
AB  - Previous reports of superoxide scavenging and ferroxidase-like activity of
      nitroxide free radicals have greatly increased interest in the ability of these
      compounds to protect cells against oxidative cellular damage. In the present
      study we investigated the antioxidant properties of the six membered nitroxide
      2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in various assays. TEMPO (5 mM)
      inhibited the hydroxyl radical mediated generation of ethylene from 2-keto-4
      methylthiobutyric acid to 31.2 +/- 4.0% of control values. Furthermore, we noted
      that TEMPO had the ability to maintain iron in its ferric form, a finding with
      strong implications for the interpretation of the ferricytochrome c reduction
      assay. TEMPO may be reduced to an electron paramagnetic resonance silent
      hydroxylamine by a number of pathways. TEMPO absorption intensity decay (TAID)
      was monitored to investigate the effects of hydrogen peroxide on Cu,Zn-SOD. TEMPO
      was found to effectively scavenge or suppress formation of hydroxyl radicals
      inside Cu,Zn-SOD. The generation of hydroxyl radical was confirmed by employing
      the conventional spin trapping agent DMPO. Using radical scavengers unable to
      penetrate the Cu,Zn-SOD enzyme (e.g., mannitol, ethanol, albumin) or compounds
      with access to copper within the Cu,Zn-SOD enzyme (azide and cyanide), we could
      not detect hydroxyl radicals outside the enzyme. Finally, since the electron
      paramagnetic resonance absorption intensity is directly proportional to the
      concentration of TEMPO spins, loss of absorption intensity provided information
      concerning radical-mediated processes. Therefore, the decay kinetics of TEMPO may
      be used as a very sensitive alternative to conventional spin traps.

PMID- 8138185
TI  - Antioxidants in the serum of children with insulin-dependent diabetes mellitus.
AB  - To determine whether alteration in serum antioxidant status is related to the
      increased oxidative stress as a cause of diabetic angiopathy, we measured both
      the antioxidant activity (AOA) and total peroxyl radical-trapping antioxidant
      parameter (TRAP), and their component individual antioxidants in serum of
      children with insulin-dependent diabetes mellitus (IDDM). The AOA was measured as
      the ability to inhibit lipid autoxidation in brain homogenates. TRAP was assayed
      as the ability to delay lipid peroxidation induced by an azo initiator.
      Antioxidants measured were ceruloplasmin, transferrin, and albumin as components
      of AOA; and ascorbic acid, uric acid, protein sulfhydryl, and alpha-tocopherol as
      components of TRAP. Serum AOA appeared to be decreased in the diabetics in
      relation to poor glycemic control, corresponding to the decrease in transferrin
      and albumin. Serum haptoglobin level was also decreased in the diabetics.
      Similarly, the directly measured TRAP value was decreased in the diabetic serum
      mainly due to the decreased contribution of unidentified chain-breaking
      antioxidants, despite the increase in ascorbic acid and alpha-tocopherol. The
      decrease in both types of antioxidant activity in the diabetic serum, as new
      findings, suggests that a defective serum antioxidant status contributes to the
      increased oxidative stress in IDDM.

PMID- 8138186
TI  - The H2O2 induced effects on purine metabolism in human endothelial cells.
AB  - The effects of hydrogen peroxide (H2O2) on the purine metabolism of human
      endothelial cells were investigated. An incubation with 0.01 mM H2O2 over 60 min
      led to an increase in the intracellular adenosine-5-triphosphate (ATP) and
      creatine phosphate (CP) levels by 51.3% and 18.2%, respectively. A 60 min
      incubation with 0.1 mM H2O2 showed no effect. The uptake and salvage of 14C
      adenine (14C-AD) and 14C-adenosine (14C-ADO) was significantly (p < 0.005)
      increased using 0.01 mM H2O2. Only an increase of 14C-ADO incorporation was
      observed using 0.1 mM H2O2. A concentration of 0.01 mM H2O2 reduced 5
      phosphoribosyl-1-pyrophosphate synthetase (PRPP-S) activity by 60% and at the
      same time increased the activity of purine nucleoside phosphorylase, which
      converts inosine to hypoxanthine (PNP I), by 24%. Adenosine kinase (AK) activity
      was reduced by H2O2, whereas adenine phosphoribosyltransferase (APRT) activity
      was found to be elevated. In conclusion, the observed elevation of cellular ATP
      and CP levels could be partially caused by an increased purine salvage resulting
      from changes in purine enzyme activities.

PMID- 8138187
TI  - Reactions of captopril and epicaptopril with transition metal ions and hydroxyl
      radicals: an EPR spectroscopy study.
AB  - In the present study, using the technique of EPR spin trapping with DMPO a spin
      trap, we demonstrated formation of thiyl radicals from thiol-containing
      angiotensin converting enzyme (ACE) inhibitor captopril (CAP) and from its
      stereoisomer epicaptopril (EPICAP), a non-ACE inhibitor, in the process of .OH
      radical scavenging. Splitting constants of DMPO/thiyl radical adducts were
      identical for both thiols and were aN = 15.3 G, and aH = 16.2 G. Bimolecular rate
      constants for the reaction of CAP and EPICAP with .OH radicals were close to a
      diffusion-controlled rate (approximately 2 x 10(10) M-1s-1). Our data also show
      that both CAP and EPICAP reduce Fe(III) ions and that their respective thiyl
      radicals are formed in this reaction. In the presence of Fe(III), H2O2, and CAP,
      or EPICAP, .OH radicals were produced by a thiol-driven Fenton mechanism.
      Copper(II) ions were also reduced by these thiols, but no thiyl radicals could be
      detected in these reactions, and no .OH or other Fenton oxidants were observed in
      the presence of H2O2. Our data show direct evidence that thiol groups of CAP and
      EPICAP are involved in scavenging of .OH radicals. The direct .OH radical
      scavenging, together with the reductive "repair" of other sites of .OH radical
      attack, may contribute to the known protective effect of CAP against
      ischemia/reperfusion-induced arrhythmias. The formation of reactive thiyl
      radicals in the reactions of the studied compounds with .OH radicals and with
      Fe(III) ions may play a role in some of the known adverse effects of CAP.

PMID- 8138188
TI  - Relationship between mitochondrial superoxide and hydrogen peroxide production
      and longevity of mammalian species.
AB  - The objective of this study was to examine the possible involvement of oxygen
      free radicals in the aging process. Rates of mitochondrial O2.- and H2O2
      production and oxygen consumption in the kidney and the heart were compared among
      seven different mammalian species namely, mouse, hamster, rat, guinea pig,
      rabbit, pig, and cow, whose maximum life span potential (MLSP) varies from 3.5 to
      30 years. The rates of mitochondrial O2.- and H2O2 generation were inversely
      correlated to MLSP, and directly related to specific metabolic rate and state 4
      mitochondrial respiration. Results of this study indicate that under identical
      conditions, mitochondria from shorter-lived species produce relatively higher
      amounts of reactive oxygen species than those from the longer-lived species, and,
      thus, support the free radical hypothesis of aging.

PMID- 8138189
TI  - Expression of manganese superoxide dismutase is not altered in transgenic mice
      with elevated level of copper-zinc superoxide dismutase.
AB  - In evaluating the relative expression of copper-zinc and manganese superoxide
      dismutase (CuZnSOD and MnSOD) in vivo in states like Down syndrome in which one
      dismutase is present at increased levels, we measured activities of both enzymes,
      in tissues of control and transgenic mice constitutively expressing increased
      levels of CuZnSOD, during exposure to normal and elevated oxygen tensions. Using
      SOD gel electrophoresis assay, CuZnSOD and MnSOD activities of brain, lung,
      heart, kidney, and liver from mice exposed to either normal (21%) or elevated (>
      99% oxygen, 630 torr) oxygen tensions for 120 h were compared. Whereas CuZnSOD
      activity was elevated in tissues of transgenic relative to control mice under
      both normoxic or hyperoxic conditions, MnSOD activities in organs of transgenic
      mice were remarkably similar to those of controls under both conditions. To
      confirm the accuracy of this method in quantitating MnSOD relative to CuZnSOD
      expression, two other methods were utilized. In lung, which is the organ exposed
      to the highest oxygen tension during ambient hyperoxia, a sensitive, specific
      ELISA for MnSOD was used. Again, MnSOD protein was not different in transgenic
      relative to control mice during exposure to air or hyperoxia. In addition, lung
      MnSOD protein was not changed significantly by exposure to hyperoxia in either
      group. In kidney, a mitochondrion-rich organ, SOD assay, before and after
      inactivation of CuZnSOD with diethyldithiocarbamate, was used. MnSOD activity was
      not different in organs from air-exposed transgenic relative to control mice. The
      data indicated that expression of MnSOD in vivo was not affected by
      overexpression of the CuZnSOD and, therefore, the two enzymes are probably
      regulated independently.

PMID- 8138190
TI  - Potential roles of hypochlorous acid and N-chloroamines in collagen breakdown by
      phagocytic cells in synovitis.
AB  - We have tested the effects of the neutrophil/macrophage products, hypochlorous
      acid (HOCl) and N-chloroamines, on the structural integrity and proteolytic
      susceptibility of collagen to determine if these agents could play a role in
      inflammatory joint destruction. Rates of HOCl reaction with collagen, and
      collagen gelation were monitored by spectrophotometric methods. Direct
      fragmentation, and degradation by collagenase were measured by the release of
      acid-soluble counts from 3H-collagen. Physiologically relevant concentrations of
      HOCl (5-50 microM) reacted rapidly and quantitatively at several sites in the
      collagen polypeptide chain, causing extensive protein fragmentation and
      preventing collagen gelation. In contrast, reaction with (5-50 microM) N
      chloroalanine induced little direct collagen fragmentation. Oxidative damage by N
      chloroamines was, however, evident because collagen displayed greatly increased
      proteolytic susceptibility following N-chloroamine treatment. Collagen
      degradation by collagenase increased as much as 3-fold after exposure to N
      chloroamine treatment. Collagen degradation by collagenase increased as much as 3
      fold after exposure to N-chloroalanine. N-chloroleucine caused a small increase
      in proteolytic susceptibility, but N-chlorotaurine had no effect. Collagen
      fragmentation by HOCl, inhibition of gelation by HOCl, and N-chloroalanine
      induced proteolytic susceptibility, all increased with linear kinetics at oxidant
      concentrations of 5 microM to 1.0 mM. In synovitis, phagocytes expose collagen to
      HOCl, N-chloroamines, and collagenase. It is known that HOCl can activate
      neutrophil procollagenase. Based on our new findings, we propose a model of
      inflammatory joint destruction that also includes collagen fragmentation, and
      increased susceptibility of collagen to degradation by collagenase.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138191
TI  - The centennial of the Fenton reaction.

PMID- 8138192
TI  - Roles of catalase and cytochrome c in hydroperoxide-dependent lipid peroxidation
      and chemiluminescence in rat heart and kidney mitochondria.
AB  - A recent report (Radi et al., J. Biol. Chem. 266:22028-22034, 1991) showed that
      rat heart mitochondria contain catalase. The protective role of mitochondrial
      catalase was tested by exposing heart or kidney mitochondria and mitoplasts to
      two oxidants (H2O2) or tert-butyl hydroperoxide, t-BOOH), estimating lipid
      peroxidation (as thiobarbituric acid-reactive substances, TBARS) and overall
      oxidative stress (as chemiluminescence). Additional controls included heart and
      kidney preparations from aminotriazole-treated (catalase-depleted) rats. Both
      oxidants increased TBARS in catalase-free preparations to similar extents over
      their respective controls (between 200 to 350%). In catalase-containing
      preparations, H2O2 lipid peroxidation increased by only 40 to 96% over controls.
      Similar qualitative results were obtained when measuring chemiluminescence. The
      catalytic role of cytochrome c in mitochondrial lipid peroxidation was
      investigated by exposing either control or cytochrome-c-depleted kidney
      mitoplasts (catalase free) to either H2O2 or t-BOOH. Hydrogen-peroxide-dependent
      mitochondrial lipid peroxidation varied with cytochrome c concentration,
      remaining close to controls when cytochrome c concentration decreased by 66%,
      even though there was no catalase present. Tert-butyl hydroperoxide-dependent
      lipid peroxidation was less affected by cytochrome c remaining 2.3-fold above
      controls under the same conditions, suggesting that organic peroxides are more
      likely to remain in the less polar membrane environment being decomposed by heme
      or nonheme iron imbedded in the inner mitochondrial membrane. Chemiluminescence
      was less affected by cytochrome c depletion. Comparing control and cytochrome-c
      deficient mitochondria, chemiluminescence was 1.7-fold and 2.8-fold higher when
      control preparations were challenged with t-BOOH or H2O2, respectively.

PMID- 8138193
TI  - Inhibition of postcardiac arrest brain protein oxidation by acetyl-L-carnitine.
AB  - Free radical mediated, site-specific protein oxidation has been implicated in the
      pathophysiology of ischemia/reperfusion brain injury. The purpose of this study
      was to determine whether this form of molecular damage could be detected in a
      clinically relevant model employing 10-min cardiac arrest in dogs followed by
      restoration of spontaneous circulation for up to 24 h. The effects of
      postischemic acetyl-L-carnitine administration on protein oxidation were also
      tested due to its previously reported improvement of brain energy metabolism and
      neurological outcome in this model. Following the experimental period, soluble
      proteins were extracted from a sample of frontal cortex and reacted with
      dinitrophenylhydrazine for spectrophotometric measurement of protein carbonyl
      groups. The most important results of this study were that brain protein carbonyl
      groups were significantly elevated following 2 and 24 h of reperfusion compared
      to nonischemic controls, and that postischemic IV administration of acetyl-L
      carnitine eliminated the increase in carbonyl groups observed at the 24-h period.
      These results indicate that brain protein oxidation does occur in a clinically
      relevant model of complete global cerebral ischemia and reperfusion, and that
      oxidation is inhibited under treatment conditions that improve neurological
      outcome.

PMID- 8138194
TI  - Increase of hydroxyl free radical formation during venous stasis of dogs.
AB  - In the passive upright position, arterial and venous pressure in human feet
      increases capillary pressure, which leads to the filtration of fluid from the
      circulating plasma into the tissues of the feet. Loss of fluid concentrates both
      red cells and plasma so that the hematocrit and plasma protein concentration of
      venous blood leaving the feet greatly exceed their mean values in the
      circulation. To study this phenomenon in animals, the authors used beagle dogs
      maintained in an upright position and compared the results to those maintained in
      a prone position. In the passive upright position, red cell count, hematocrit,
      and total plasma protein concentrations were significantly increased. Therefore,
      we have determined the level of hydroxyl free radical formed as assessed by
      salicylate hydroxylation in the saphenous vein of dogs in an upright and normal
      position. Hydroxyl free radical formation was significantly higher in the veins
      of dogs in an upright position than in those in a prone position. The upright
      position model, which causes increases in hematocrit red cell count and total
      plasma protein in the saphenous vein, seems suitable for the study of drugs
      interfering in the pathophysiology of venous stasis. Indeed, the hematocrit
      increase of red cell count and total plasma protein in the saphenous vein of the
      beagle is similar to modifications observed in venous blood leaving the human
      foot after sitting. Moreover, the increase of .OH, concomitant with these
      modifications, may explain certain pathological observations, for instance,
      edema. The data clearly suggest that macromolecular extravasculation may be due
      to tissue injury caused by oxygen free radical formation in the blood vessels.

PMID- 8138195
TI  - Adenosine deaminase, 5' nucleotidase, xanthine oxidase, superoxide dismutase, and
      catalase activities in cancerous and noncancerous human laryngeal tissues.
AB  - We determined activities of adenosine deaminase (ADA), 5' nucleotidase (5NT),
      xanthine oxidase (XO), superoxide dismutase (Cu-Zn SOD), and catalase (CAT)
      enzymes in 15 human laryngeal tissues with well-differentiated squamous cell
      carcinomas, in 15 corresponding tumor-free adjacent tissues and in 7 normal
      laryngeal tissues. We found lower ADA and 5NT and higher XO, Cu-Zn SOD, and CAT
      activities in cancerous tissues than those in corresponding noncancerous ones. In
      the correlation analysis, we established one positive intercorrelation, which was
      between ADA activities of tumor tissues and noncancerous adjacent tissues. We
      also found some significant intracorrelations between enzyme activities of the
      tissues, all of which were positive in cancerous ones.

PMID- 8138196
TI  - Health effects of nutritional antioxidants.

PMID- 8138197
TI  - [Nd:YAG laser for anorectal surgery: initial experience in Israel].
AB  - The use of laser in gastrointestinal diseases started in the mid-70's. The 3
      types of laser in use today are CO2, argon and Nd:YAG. We present the first
      clinical results in Israel of the use of the Nd:YAG laser in anorectal surgery.
      Between Oct. '91-Dec. '92, 275 patients with anorectal diseases (mostly
      hemorrhoids, anal fissures and fistulas) and 67 with various perineal lesions
      were operated on. Within an hour of the end of the operation, most patients were
      discharged to home with detailed follow-up instructions. 8 needed an extra day of
      observation in hospital. Postoperative complications included: bleeding (8
      patients), wound infection (4) and urinary retention after hemorrhoidectomy (8).
      1 patient complained of anal laxity after sphincterotomy, and 4 of recurrence of
      anal fissure. It is our impression that after laser hemorrhoidectomy patients
      return quickly to their normal lives; that the rate of complications is not
      greater than after other accepted techniques; and that the laser method for anal
      fistulectomy is most efficacious.

PMID- 8138198
TI  - [Percutaneous, CT-guided excision of femoral osteoid osteoma].
AB  - An osteoid osteoma in the distal femur of a 10-year-old girl was excised,
      percutaneously, under CT guidance. Location of the nidus was by insertion of a
      Kirshner wire under CT control. Hollow Mill was used to excise the nidus by
      drilling over the Kirshner wire, with CT guidance during each stage. There were
      no complications and pain ceased overnight. Follow-up after 4 months showed
      complete recovery and no pain.

PMID- 8138199
TI  - [Acute psychiatric hospitalization due to alcoholism, 1978-1988].
AB  - We examined the records of 81 alcoholic patients hospitalized a total of 260
      times (3.2 per patient) during 1978-1988. Hospitalizations were of the acute
      type, and not for weaning purposes. Only 1 of the patients was born in Israel.
      The prevalence of hospitalizations involving alcoholism among immigrants from the
      former Soviet Union, North Africa, and South America was similar, 0.07%. However,
      in immigrants from India and Pakistan it was 0.4%. 10% of hospitalizations were
      ordered by court or district psychiatrists. There were 69 men and 12 women (M/F
      ratio 5.8). In 1171 of the hospitalizations, one-third were later found not to be
      of alcohol-related. We therefor emphasize the need for better clinical diagnosis.
      The relationship between age on immigration and age on first psychiatric
      hospitalization for alcoholic psychosis indicated a group of "imported"
      alcoholics. In light of the continuing immigration from countries with a high
      incidence of alcoholism to Israel, an appropriate system should be set up to
      prevent and to treat alcoholism.

PMID- 8138200
TI  - [Mitochondrial creatine-kinase--an isoenzyme in trouble].

PMID- 8138201
TI  - [Karyotypic aberrations in gynecological malignancies].

PMID- 8138202
TI  - [Toxoplasmosis acquired during pregnancy].

PMID- 8138203
TI  - [The diagnostic criteria of unequal distribution of deficits in vascular
      dementia: operationally possible?].

PMID- 8138204
TI  - [Conversive hallucinations].

PMID- 8138205
TI  - [Cholesteatoma of the kidney--update].

PMID- 8138206
TI  - [Cigarette smoking increases the risk of developing cataract].

PMID- 8138207
TI  - [Large simple liver cyst treated laparoscopically].
AB  - Simple liver cysts of various sizes are present in 1% of the population. Most are
      found incidentally and require no treatment. However, in a few the cyst is
      symptomatic and requires surgery: celiotomy and unroofing of the cyst. A 64-year
      old woman with a symptomatic, simple cyst of the liver underwent laparoscopic
      surgery. After an uneventful course she was discharged on the 3rd postoperative
      day. Simple liver cysts can be safely treated by laparoscopic surgery.

PMID- 8138209
TI  - [New secondary psychiatric legislation].

PMID- 8138208
TI  - [Endoscopic ultrasonography of the upper gastrointestinal tract].

PMID- 8138210
TI  - [Rheumatic fever and Jones criteria 1992].

PMID- 8138211
TI  - [Visual hemineglect as presenting symptom of right parietal tumors].
AB  - 4 patients with malignant right parietal brain tumors (2 with gliomas and 2 with
      metastases) presented with difficulties in driving due to visual hemineglect,
      thought at first to be due to absent-mindedness or forgetfulness. Visual neglect
      is one aspect of the syndrome of unilateral neglect, which is a selective
      disturbance in the internal representation of the body image and processing of
      information from the extrapersonal space. The cerebral mechanisms underlying the
      phenomenon are reviewed.

PMID- 8138212
TI  - [AIDS-related knowledge, behavior and attitudes of workers in Israel].
AB  - Control of the AIDS pandemic depends largely on the success of educational
      programs designed to persuade the population at risk to use currently recommended
      methods of prevention. In Israel there are no regular national surveys on the
      health-related behavior of the population. The consequent lack of reliable data
      makes it difficult both to develop and to evaluate AIDS-related educational
      programs. A survey was therefore conducted among 536 employees of 3 workplaces in
      Dec. 1992, using anonymous questionnaires. The level of general knowledge of the
      disease was good, although in selected areas there were deficiencies: more than
      20% of the men and 40% of the women believed that AIDS can be contracted through
      the use of public toilets. More than 50% of the subjects indicated that they
      would like more information on the disease, and believe that insufficient
      education is given youth regarding the use of the condom. Women tended to be more
      worried than men about the possibility of contracting AIDS, and were more likely
      to adopt preventive behavior and educate their children in this regard. These
      findings indicate the need to design separate educational programs for men and
      women. Further on-going surveys in representative samples of the general
      population are urgently needed to monitor trends in AIDS-related knowledge,
      attitudes and behavior.

PMID- 8138213
TI  - Hair analysis as a diagnostic tool for drugs of abuse investigation. Proceedings
      of the 1st International Meeting, Genoa, Italy, 10-11 December, 1992.

PMID- 8138214
TI  - Drug distribution in the head, axillary and pubic hair of chronic addicts.
AB  - This study investigates the distribution of some drugs in hair samples taken from
      different parts of the body (head, pubis and axillae). Samples drawn from 15
      subjects who died from drug overdose were analysed. The concentrations of the
      drugs detected in the biological fluids did not appear to be correlated with
      those present in hair. The highest drug levels were observed in pubic hair. The
      concentration differences observed in the various types of hair can
      hypothetically be ascribed to a likely incorporation of the drugs from the
      outside.

PMID- 8138215
TI  - Sample preparation techniques.
AB  - Evidentiary false positives are caused by passive exposure to drugs in the
      environment rather than by active use of drugs. The avoidance of such positives
      is essential for both hair and urine analysis. Hair analysis enjoys the advantage
      over urinalysis in having a number of approaches for making this distinction.
      These include: methylene blue staining of the hair specimen for selecting the
      appropriate wash solvent; application of hair digestion techniques for the
      complete release of chemically unaltered analytes; the determination of three
      diagnostic ratios from wash and digestion data; the measurement of
      metabolite:drug ratios; the use of cut-off levels setting the limits for passive
      endogenous drug exposure; reproducibility of results (including segmental
      analysis) with a newly collected hair specimen; and the reporting of results as
      either negative, positive, or contaminated. Our sample preparation procedures
      have been effectively applied to the analyses of nearly 200,000 specimens, i.e.
      to approximately one million drug analyses for cocaine, opiates, methamphetamine,
      phencyclidine or marijuana. On the basis of this experience we conclude that hair
      analysis is a safe and effective method for workplace drug testing.

PMID- 8138216
TI  - External contamination of hair by cocaine: an issue in forensic interpretation.
AB  - This paper explores the variables by which hair samples may become contaminated
      with cocaine and thereby generate false positives during analysis of hair
      samples. A novel method for following the incorporation and removal of cocaine
      from hair was developed. This method allowed a large number of specimens to be
      analysed under a variety of conditions with high precision. The quantity of
      cocaine was carefully followed in each step of a published procedure. Regardless
      of washing technique, a substantial amount of cocaine could still be found in the
      final hair digest. Very few of our externally contaminated samples could be
      identified as externally contaminated by previously published criteria and
      washing procedures. Attempts to further decontaminate this hair were without
      success. Our data strongly suggest that external contamination of hair by drugs
      of abuse may make the interpretation of forensic results problematical.

PMID- 8138217
TI  - Overview on extraction procedures.
AB  - The literature reviewed shows that many of the analytical problems related to the
      toxicological analysis of hair have been resolved, but in some cases, as for the
      application of the extraction methods, it is worth highlighting that the
      parameters must be carefully valued owing to the different operative options that
      are documented in the literature. Besides, the choice of a suitable extractive
      procedure may be influenced by various factors, including the following: (i) the
      type of drug which the analysis is targeted at and its characteristics of
      stability in different hydrolytic systems; (ii) ratio of distribution of the
      abused substances and their metabolites in the hair; and (iii) method used for
      the subsequent qualitative and quantitative analysis. Hence the selection of the
      extraction method requires some considerations, particularly when this kind of
      analysis is used in the forensic field. In this regard, emphasis is actually
      placed on pharmacokinetic incorporation and retention of drugs into hair.
      Furthermore, lacking any source of certified reference material, more studies
      concerning the recovery, accuracy and, if possible, quality control programs,
      could be implemented in order to test each procedure and improve the reliability
      of the extraction steps in the toxicological analysis of hair.

PMID- 8138218
TI  - Improved enzymatic hydrolysis of hair.
AB  - An enzymatic hair extraction method is proposed for drug analysis. Pronase
      digestion of various aliquots of hair from a cocaine abuser was preceded by a 2-h
      incubation with a dithiothreitol solution. The extraction solution was tested to
      identify possible interferences in the radioimmunoassay and was compared with
      other hydrolysis methods to assess the results of extraction.

PMID- 8138219
TI  - Analytical requirements, perspectives and limits of immunological methods for
      drugs in hair.
AB  - The analytical requirements for analysis of drugs in hair are sensitivity in the
      range of picograms per milligram of hair, specificity for lipophilic drugs and
      absence of matrix effects with hair digests. These requirements are met by
      immunoassays which are also inexpensive, rapid and easy to use. However, in
      applying immunoassays to hair testing, certain limitations of the assay and of
      interpretation of assay results should be kept in perspective. These limitations
      are illustrated in this review with examples of the analysis of opiates in hair
      from patients and opiate addicts. The first requirement for immunological
      analysis of hair digests is that the digest must not denature the antibody
      proteins of the immunoassay reagents. For this reason enzymatic digests are
      better for immunological assay than chemical digests. Strongly acidic or alkaline
      digests must be brought to a neutral pH before immunoassay. Immunoassays used for
      analysis of hair should be calibrated with spiked hair digest standards to
      correct for possible matrix effects. The second requirement is that the
      immunoassay have the sensitivity and specificity to detect the drug in hair.
      Drugs of abuse are found in hair in the range of 10 pg-10 ng/mg hair.
      Radioimmunoassays are capable of detection and quantitation in this concentration
      range. Although the mechanism of drug incorporation into hair is not known, it is
      now apparent that primarily the parent drug and lipophilic metabolites are found
      in hair. For example, the ratio of cocaine/benzoylecgonine averages 10 (range 2
      50) in published reports of analysis of hair from cocaine users. Therefore,
      immunoassays which are highly sensitive for the parent drug are required and
      results of immunoassays should be expressed as equivalents. When spiking
      standards for calibration of hair digest immunoassays, parent drug known to be
      present in hair should be used, e.g. cocaine not benzoylecgonine. With
      immunoassays which are specific for the lipophilic metabolite found in hair such
      as 6-MAM, differential radioimmunoassay can be used to discriminate between
      medical and illicit sources for the opiate drugs found in hair. Because of the
      low concentrations of drugs encountered in hair, immunoassays for hair have been
      used at cutoff concentrations at their limits of detection. The limit of
      detection (LOD) has been determined by calculating the mean and standard
      deviation (S.D.) for the assay response for a number of negative hair samples.
      The cutoff was then set at a distance of 2, 3, or 5 S.D.s from the mean
      response.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8138220
TI  - Simultaneous determination of drugs of abuse (opiates, cocaine and amphetamine)
      in human hair by GC/MS and its application to a methadone treatment program.
AB  - A new method was developed for the simultaneous detection and quantitation of 6
      acetyl-morphine (MAM), amphetamine, benzoylecgonine (BZE), cocaine, codeine,
      dihydrocodeine, EDDP (methadone metabolite), methadone and morphine in hair. The
      hair samples were washed, cut into 2-cm segments, pulverized, incubated with
      phosphate buffer and beta-glucuronidase/aryl-sulfatase. After solid phase
      extraction and derivatization with pentafluoropropionic
      anhydride/pentafluoropropanol, the drugs were identified and measured by gas
      chromatography/mass spectrometry using their deuterated analogues as internal
      standards. The method is reproducible with detection limits under 0.1 ng/mg hair
      for almost all substances tested. Fifteen hair samples from five subjects of a
      methadone treatment program were collected in a 6-month period. The hair samples
      were segmented and examined for methadone, its main metabolite EDDP, and drugs of
      abuse. Of the 96 segments analysed, 95% were positive for methadone (mean value,
      10.9 ng/mg), 76% for the metabolite EDDP (mean value, 1.2 ng/mg), 69% for opiates
      (mean values, MAM, 7.3 ng/mg; morphine, 2.9 ng/mg; codeine, 1.0 ng/mg) and 43%
      for cocaine (mean values, cocaine, 2.6 ng/mg; BZE, 1.1 ng/mg). A correlation of
      0.63 was found between administered methadone dosages and concentrations measured
      by hair analysis. Further investigation is needed to clarify interindividual
      differences.

PMID- 8138221
TI  - Mechanisms of drug incorporation into hair.
AB  - The model generally proposed to explain the incorporation of drugs into hair is
      one in which drugs enter hair only by passive diffusion from the blood stream
      into the growing cells at the base of the hair follicle. However, this model may
      be over-simplified. More recent experimental findings suggest that drugs may
      enter hair from multiple sites, via multiple mechanisms, and at various times
      during the hair growth cycle. A more complex model is proposed in which drugs and
      metabolites are incorporated into hair during formation of the hair shaft (via
      diffusion from blood to the actively growing follicle), after formation (via
      secretions of the apocrine and sebaceous glands), and after hair has emerged from
      the skin (from the external environment). Further, drugs can be transferred to
      hair from multiple body compartments or pools located in tissues surrounding the
      hair follicle. These mechanisms could also be drug-specific. A more precise
      understanding of the mechanisms involved in the incorporation of drugs into hair
      is critical for forensic scientists in order to interpret the results of hair
      analysis properly.

PMID- 8138222
TI  - Comparison of quantitative results of drugs in human hair by GC/MS.
AB  - Until the first determination of opiates in human hair by GC/MS in 1985,
      radioimmunological results of hair examinations met with opposition. Since then,
      further GC/MS methods have been developed that have led not only to considerably
      increased sensitivity, but can also be used in hair analysis for screening
      purposes and can detect substances for which RIA kits are not available. In the
      present study different extraction methods were used along with two GC/MS
      processes which back-up each other. These methods include the enzymatic
      dissolution of the hair, incubation with a buffer solution followed by a solid
      phase extraction and incubation with methanol without a further extraction. The
      GC/MS examination for heroin, cocaine, hashish and selected pharmaceuticals was
      carried out after derivatization with pentafluoropropionic acid anhydride or
      pentafluoro-1-propanol. Because of the higher sensitivity and versatility of
      GC/MS, two GC/MS processes were used to confirm each other instead of backing-up
      radioimmunological measurements with GC/MS.

PMID- 8138223
TI  - Rapid and highly selective GC/MS/MS detection of heroin and its metabolites in
      hair.
AB  - A direct treatment of methanol-washed hair with a silylating solution is proposed
      to extract heroin, O-6-monoacetylmorphine, morphine, acetylcodeine, and codeine,
      obtaining the simultaneous derivatization of the hydroxylated metabolites and
      reducing potential sample contamination. Analysis is performed by capillary gas
      chromatography-tandem mass spectrometry (GC/MS/MS) using multiple selected
      reaction monitoring. Owing to the selectivity and sensitivity of the GC/MS/MS
      analysis, and to the extremely simple treatment of the sample, the method fulfils
      the requirements of both clinical and forensic diagnosis of heroin use.

PMID- 8138224
TI  - High-sensitivity low-cost methods for determination of cocaine in hair: high
      performance liquid chromatography and capillary electrophoresis.
AB  - Free solution capillary electrophoresis and high performance liquid
      chromatography were applied to the analysis of cocaine in hair. Capillary
      electrophoresis conditions were as follows. Background electrolyte: 0.050 M
      borate, pH 9.2; capillary: bare silica, 40 cm long, 50 micrograms i.d.;
      potential: 15 kV; detection: UV at 238 nm wavelength. In addition, the separation
      was accomplished in a 50 cm x 75 microns capillary with an instrument with a
      photodiode array detector, recording on-line UV spectra of peaks from 200 to 400
      nm. The isocratic high performance liquid chromatographic method with
      fluorimetric detection used 230 nm (ex.) and 315 nm (em.) wavelengths. Cocaine
      separation was carried out under conditions summarized as follows: column packed
      with spherical polystyrene-divinylbenzene 5 microns particles, mobile phase 0.1 M
      potassium phosphate (pH 3.0)/methanol/THF (70:25:5) at a flow rate of 0.5 ml/min
      and at room temperature. Liquid-liquid and solid-liquid sample preparation
      methods were used. Typically, levels of cocaine in hair as low as 0.15-0.30 ng/mg
      were detected by capillary electrophoresis, while HPLC allowed the determination
      of concentrations lower by one order of magnitude (0.015 ng/mg). Intra- and inter
      assay precision data of the two techniques were comparable and characterized by
      relative standard deviations in the range from 3 to 7%. On the other hand, the
      sample throughput of capillary electrophoresis (7-10 injections/h) was higher
      than high performance liquid chromatography (2 injections/h). A good correlation
      of the results (r2 = 0.92) between the two techniques was observed in the assay
      of real cases.

PMID- 8138225
TI  - Ion trap mass spectrometry, a new tool in the investigation of drugs of abuse in
      hair.
AB  - The use of an ion trap mass spectrometer for the detection, via tandem mass
      spectrometry, of morphine and cocaine in the hair of drug addicts proved to be
      successful. In particular, detection limits of 1-20 ppb for morphine and 5-30 ppb
      for cocaine were achieved, with good reproducibility and absence of interferent
      species.

PMID- 8138226
TI  - Utilization of hair analysis for therapeutic drug monitoring with a special
      reference to ofloxacin and to nicotine.
AB  - Human scalp hair retains the past dosage history over a rather long period of
      time, acting as 'tape-recorder'. Each 1-cm length of hair contains the drug
      approximately corresponding to the amount ingested over a 1-month period when the
      hair is cut into 1-cm lengths successively from the scalp end. However, the hair
      growth rate is variable both within and between subjects and the hair has its own
      growth cycle. Therefore, the validity of obtained results must always be
      considered cautiously, especially in relation to whether resting-stage hair might
      have been sampled. It has been found that antimicrobial quinolones are detectable
      in hair, even after a short exposure to them, and serve as time marker for
      estimating the growth rate itself and the stage of hair. By analysing the axial
      distribution of ofloxacin-one of the most frequently prescribed quinolone
      derivatives in Japan-along the hair shaft, the 'tape-speed' and 'uniformity of
      tape-running' of a single hair can be estimated. Research into cigarette-smoking
      behavior necessitates accurate measurement of smoking habit. It has been found
      that the nicotine content in hair is proportional to the number of cigarettes
      consumed daily. Moreover, the cm-by-cm analysis of axial nicotine distribution
      along the hair shafts revealed the concentrations of nicotine approximately
      proportional to the month-by-month self-report on daily-consumed cigarettes in a
      subject who participated in a smoking-cessation program.

PMID- 8138227
TI  - Cocaine and metabolites in the hair of ancient Peruvian coca leaf chewers.
AB  - Cocaine and its metabolites, benzoylecgonine (BZE) and ecgonine methylester
      (EME), were found in hair samples from ancient Peruvian coca-leaf chewers dating
      back to AD 1000. Hair was analyzed by gas chromatography/mass spectrometry
      (GC/MS) to quantitate the concentrations. The two metabolites were found in
      higher concentration than the parent drug. The metabolite levels appear to be
      below that of modern cocaine abusers. Gender does not appear to be a factor in
      the incorporation of drug into hair.

PMID- 8138228
TI  - Hair analysis as a tool for monitoring and managing patients on methadone
      maintenance. A discussion.
AB  - Hair analysis for unprescribed drugs is not merely an effective, dignified, and
      time-saving alternative to urine testing. It is also more sensitive and more
      difficult to evade and minimises the risk of infection to clinic staff. Because
      of these characteristics, it can, when properly used, change the nature of the
      relationship between treatment personnel and patients on methadone maintenance.
      These changes can be beneficial and acceptable to both parties. In 263 patients,
      41% of hair samples were negative for opiates, 22% had levels below 10 ng/10 mg,
      while in a further 7% the level was less than 20 ng/10 mg. The existing and
      potential advantages of this technique in managing both opiate abuse and other
      sorts of drug abuse are discussed.

PMID- 8138229
TI  - Antibodies to drugs as indicators of chronic drug use. An alternative to
      toxicological hair analysis.
AB  - An ELISA method for detection of specific antibodies to morphine-protein
      conjugate (MPC) in humans and animals was elaborated. In humans, antibodies could
      be detected predominantly as the IgM class of immunoglobulins. Elevated levels of
      such antibodies were found in about 50% of opiate addicts and morphine-treated
      rats. In the case of prolonged and regular drug use with the time since the last
      drug intake not exceeding 2 months, elevated levels of antibodies to MPC were
      detected more frequently (up to 75%). Antibodies to MPC, detected in opiate
      addicts, were specific to MPC, morphine and beta-endorphin. A similar approach
      was applied to the detection of antibodies to ephedrone (amphetamine-like
      derivative of ephedrine) in case of its chronic use.

PMID- 8138230
TI  - Interlaboratory comparison studies on the analysis of hair for drugs of abuse.
AB  - Eleven laboratories interested in the analysis of human hair for drugs of abuse
      participated in a study to determine how well drugs could be detected and
      quantified in hair. For the two exercises completed to date, substances to be
      determined were limited to cocaine, benzoylecgonine, and morphine. Samples sent
      to the participating laboratories included hair from drug users, drug-free hair,
      and hair into which drugs had been soaked. For the first exercise, the hair
      samples were sent as powders; for the second, they were in the form of short
      segments. Results from these studies have shown that the laboratories, with a few
      exceptions, have performed very well qualitatively. However, scatter in
      quantitative results was high. Various approaches were used to liberate drugs
      from the hair, with the most commonly used, acid extractions and enzyme
      digestions, producing similar results. Laboratories using GC/MS generally
      performed well and reported no false positives. In contrast, one laboratory
      analyzing hair directly using MS/MS without extractions produced three of the
      four false positives and the worst quantitative results.

PMID- 8138231
TI  - Importance of quality assurance in testing drugs of abuse.

PMID- 8138232
TI  - Hair analysis--perspectives and limits of a proposed forensic method of proof: a
      review.
AB  - In the last few decades, a significant trend has been the self-administration of
      drugs to 'get high' or to achieve other desired pleasurable effects. This trend
      has produced major efforts to combat drug misuse or abuse. One such effort has
      been to utilize analytical toxicology to identify individuals who abuse drugs.
      Recognizing that individuals who abuse drugs might report for work in an impaired
      condition and create risk for themselves, for co-workers, or for others around
      them, many employers have established programs to deter drug use by their
      employees. These programs often include collection of a urine specimen and
      analysis of that specimen for drugs of abuse. Recently, some investigators have
      proposed that hair samples should be used in place of, or in addition to, urine
      samples for this purpose. Among the subjects which are relevant to utilizing hair
      as a specimen for detection of drugs of abuse and which will be covered in this
      review are the following: hair morphology and growth; which analyte--parent or
      metabolite(s); specimen collection and preparation; external contamination;
      comparison/standard specimens; segmental vs. whole hair analysis; and
      interpretation of results.

PMID- 8138233
TI  - Hair analysis as evidence in forensic cases.
AB  - Because hair analysis can be used for the determination of drug use months after
      drug consumption, hair analysis data can often act as important and even decisive
      evidence in the courtroom. More recently developed GC/MS methods offer excellent
      sensitivity and can make the distinction between chronic heroin and codeine use,
      which was not possible earlier with radioimmunoassay techniques. From more than a
      thousand hair analyses, the morphine/codeine ratios necessary to determine heroin
      use were set at 5:1 for low morphine concentrations (< 1 ng/mg hair) and 2:1 for
      concentrations above 1 ng/mg hair. The distinction can be further focused with
      the additional analysis of the metabolite monoacetylmorphine (MAM). As can be
      seen from several case examples, hair analysis cannot pinpoint an exact date of
      opiate use, but it can be used to validate or invalidate a subject's statement
      concerning his/her drug consumption. Interpretations should always be made
      cautiously. Ranges, means and medians are also listed for amphetamine, cocaine
      and cannabis and work is under way to draw similar safety guidelines for these
      drugs.

PMID- 8138234
TI  - The occurrence of cocaine, heroin and metabolites in hair of drug abusers.
AB  - The analysis of hair for drugs of abuse reveals information regarding past drug
      exposure. We developed methods for washing, extraction and analysis of hair
      samples for cocaine, heroin and metabolites. Twenty paired head- and arm-hair
      samples, collected from known heroin/cocaine abusers, were analyzed with a new
      comprehensive GC/MS assay for cocaine, heroin and metabolites. Cocaine and 6
      acetylmorphine (6-AM) were the major analytes present in both head- and arm-hair
      samples. Cocaine was detected in all head- and 17 arm-hair samples. The
      concentration of cocaine found was 4-760 ng/10 mg in head hair and 0-1090 ng/10
      mg in arm hair. Less benzoylecgonine was present in a concentration range of 0
      158 ng/10 mg of head hair and 0-125 ng/10 mg of arm hair. Heroin was found in
      only 2 head-hair samples, whereas 6-AM was present in 14 head and 6 arm-hair
      samples. The concentration of 6-AM was 0-8 ng/10 mg in head hair and 0-31 ng/10
      mg in arm hair. Morphine was present in 3 head-hair samples in a range of 2-9
      ng/10 mg and was not detected in arm-hair samples. When results were compared by
      groups (head hair versus arm hair, Caucasoid versus Africoid), only two
      significant differences were found. Cocaine concentrations in both head and arm
      hair were significantly (P < 0.05) higher in the Africoid group than in the
      Caucasoid group. The reasons for these differences were not readily apparent, but
      could have been due to differences in the level of cocaine use or to ethnic
      differences in the deposition of drug in hair.

PMID- 8138235
TI  - Hair analysis: its importance for the diagnosis of poisoning associated with
      opiate addiction.
AB  - In forensic toxicology, hair analysis for determining intoxication by inorganic
      substances has received much attention. Organic substances, on the other hand,
      are also found in hair and therefore hair should be regarded as an important
      source for evaluation of drug use. This paper examines the advantages and
      limitations of hair analysis in the measurement of opiates by using hair taken
      from some actual drug users in Switzerland.

PMID- 8138236
TI  - Variability of opiates concentrations in human hair according to their anatomical
      origin: head, axillary and pubic regions.
AB  - The concentrations of morphine and codeine were investigated in hair from the
      head, axillary and pubic regions obtained from 20 fatal heroin cases. Hair
      preparation involves decontamination procedure in dichloromethane at 37 degrees C
      for 15 min, solubilization in sodium hydroxide at 100 degrees C for 5 min,
      neutralization with hydrochloric acid and centrifugation. After extraction in
      chloroform/isopropanol/n-heptane (50:17:33; v/v) at pH 9.2, drugs were
      derivatized with BSTFA + 1% TMCS and separated on a 12-m BP-5 capillary column.
      Quantification was done by GC/MS using selected ion monitoring. The highest
      morphine concentrations were found in public hair (0.80-41.34 ng/mg), followed by
      hair of the head (0.62-27.10 ng/mg), and axillary hair (0.40-24.20 ng/mg).
      Codeine was also detected in all samples, and the codeine/morphine ratios ranged
      from 0.54 to 0.273. The differences observed in drug concentration in the three
      kinds of hair are discussed in the light of the existing literature.

PMID- 8138238
TI  - Anatomy and physiology of hair.
AB  - To interpret the results of hair analysis tests accurately and to understand the
      appropriate role of hair analysis in drug abuse testing, a basic understanding of
      the biology of hair is necessary. Although hair may appear to be a simple
      structure, it is actually a complex part of the anatomy whose biology is only
      partially understood. Hair grows from small organs (follicles) located within the
      complex microenvironment of the skin which has multiple layers of tissue, three
      glands whose secretions bathe hair, and multiple vascular systems which are
      capable of transferring drugs to hair at many levels along the length of the hair
      shaft. The advantages and disadvantages of using scalp, beard, or pubic hair as
      specimens for hair analysis are also considered.

PMID- 8138237
TI  - An evaluation of patterns of racial bias in hair assays for cocaine: black and
      white arrestees compared.
AB  - This article evaluates the hypothesis that hair assays for cocaine will evidence
      a racial bias. It compares the outcome of hair and urinalysis assays for cocaine
      metabolites in a group of white and a group of black arrestees in Pinellas
      County, Florida on whom detailed self-reported drug use is known. The findings
      indicate that although blacks test at higher positive rates than whites for both
      hair and urine assays, these differential most likely reflect differential rates
      of use of cocaine which is apparent from the self-reported data.

PMID- 8138239
TI  - Evidence of gestational heroin or nicotine exposure by analysis of fetal hair.
AB  - Failure to identify tobacco- or heroin-exposed neonates is extensive owing to the
      limitations of current methods used to verify maternal drug use. Maternal self
      reported drug history has been shown to be unreliable: many women who deny use
      during pregnancy exhibit drug metabolites in their urine. Maternal systematic
      urinalysis is hampered by the short elimination half-life of the drugs. This test
      is not suitable for validation of survey data since the quantification of drugs
      in urine only reflects exposure during the preceding 1-3 days and does not
      necessarily indicate the frequency in subjects who might deliberately abstain for
      several days before biomedical screenings. The same disadvantages are noted with
      the analysis of babies' meconium, or the amniotic fluids which are only a
      qualitative test at the moment of delivery. Hair analysis remedies the
      disadvantages of these currently available methods by exhibiting a wide window of
      detection and may provide information concerning the severity of gestational
      exposure. Hair samples were collected at time of delivery from 40 and 9 neonates
      whose mothers were known, by self-report, to be smokers and heroin users during
      the prenatal period, respectively. Hair was decontaminated in dichloromethane (37
      degrees C, 15 min) and homogenizated in NaOH (1 M, 10 min, 90 degrees C).
      Nicotine and opiates were extracted in diethylether at pH 14, and in
      chloroform/isopropanol/n-heptane (50:17:33 v/v) at pH 9.2, respectively. After
      separation on a BP-5 capillary column, drugs were identified and quantified by
      GC/MS using selected ion monitoring. The ranges of measured concentrations were
      0.15-11.80 and 0.61-3.47 ng/mg for nicotine and morphine, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138240
TI  - Tauro alpha-muricholate is as effective as tauro beta-muricholate and
      tauroursodeoxycholate in preventing taurochenodeoxycholate-induced liver damage
      in the rat.
AB  - Male Wistar rats were infused intravenously with taurochenodeoxycholate (0.4
      mumol/min/100 gm) alone (group A) or with one of the three bile salts
      (tauroursodeoxycholate [group B], tauro beta-muricholate [group C] or tauro alpha
      muricholate [group D]) at a rate of 0.2 mumol/min/100/gm for 1 hr. One-hour bile
      flow and bile salt excretion rates were significantly lower in group A than in
      the other three coinfused (B, C, D) groups. Biliary 1-hr outputs of lactate
      dehydrogenase and albumin in the bile, on the other hand, were significantly
      higher in group A than in the other groups. Plasma concentrations of lactate
      dehydrogenase at the time of killing (1 hr) were two to three times higher in
      group A than in the other groups. Although tauro alpha-muricholate does not
      possess a 7 beta-hydroxy group, the 6 beta-hydroxy group that tauro alpha
      muricholate possesses thus appears to be as effective as a 7 beta-hydroxy group
      in reducing the liver damage caused by toxic bile salts such as
      taurochenodeoxycholate. The so-called hepatoprotective effects of
      tauroursodeoxycholate and tauro beta-muricholate found in previous studies may
      require explanation(s) other than the presence of a 7 beta-hydroxy group in their
      molecular structures.

PMID- 8138241
TI  - Comparison of peptidoglycan-polysaccharide and lipopolysaccharide stimulation of
      Kupffer cells to produce tumor necrosis factor and interleukin-1.
AB  - Endotoxin (lipopolysaccharide) is a cell wall polymer from gram-negative bacteria
      that stimulates Kupffer cell release of cytokines such as tumor necrosis factor
      alpha and interleukin-1. Another bacterial cell wall polymer in both gram
      negative and gram-positive organisms is peptidoglycan-polysaccharide.
      Lipopolysaccharide and peptidoglycan-polysaccharide exist together in the
      intestinal lumen and can cross the intestinal mucosa, enter the portal vein and
      activate Kupffer cells. The purpose of this study was to compare the effects of
      lipopolysaccharide stimulation and peptidoglycan-polysaccharide stimulation of
      Kupffer cells on release of tumor necrosis factor-alpha and interleukin-1. Both
      bacterial polymers caused maximum tumor necrosis factor-alpha release from
      Kupffer cells after incubation for 4 to 8 hr. Maximum tumor necrosis factor-alpha
      release induced by 400 ng/ml lipopolysaccharide was 704 +/- 258 pg/ml, compared
      with 329 +/- 91 pg/ml tumor necrosis factor-alpha after 100 micrograms/ml
      peptidoglycan-polysaccharide (p < 0.001). Polymyxin B blocked lipopolysaccharide
      stimulation of tumor necrosis factor-alpha by 95% +/- 5% but blocked
      peptidoglycan-polysaccharide-stimulated tumor necrosis factor-alpha by 30% +/-
      14% (p < 0.001). Repeat incubation of Kupffer cells with lipopolysaccharide after
      prior lipopolysaccharide incubation induced low tumor necrosis factor-alpha
      release (tolerance). Repeat incubation with peptidoglycan-polysaccharide induced
      no tolerance to tumor necrosis factor-alpha release. Incubation of
      lipopolysaccharide plus peptidoglycan-polysaccharide released less tumor necrosis
      factor-alpha than did each polymer used alone, but this inhibition was prevented
      by indomethacin. Dibutyryl cyclic AMP, prostaglandin E1, prostaglandin E2 and the
      adenosine A2-receptor agonist N-ethylcarboxyamideadenosine inhibited
      lipopolysaccharide-stimulated tumor necrosis factor-alpha release by 83%, 97%,
      90% and 94%, respectively, but inhibited peptidoglycan-polysaccharide-stimulated
      tumor necrosis factor-alpha release by 52%, 60%, 45% and 51%, respectively (p <
      0.001 for each). This indicates that intracellular signaling pathways differ for
      lipopolysaccharide-stimulated and peptidoglycan-polysaccharide-stimulated tumor
      necrosis factor-alpha release. After incubation for 8 and 24 hr, 100
      micrograms/ml peptidoglycan-polysaccharide had induced significantly more
      interleukin-1 release from cultured Kupffer cells than had 400 ng/ml
      lipopolysaccharide (p < 0.001). Lipopolysaccharide induced tolerance to
      interleukin-1 release after repeat incubation, but peptidoglycan-polysaccharide
      caused no tolerance. These studies show that peptidoglycan-polysaccharide, a
      ubiquitous bacterial cell wall polymer, shares several proinflammatory properties
      with lipopolysaccharide but that there are differences that may have
      pathophysiological significance.

PMID- 8138242
TI  - A new three-dimensional culture system for hepatocytes using reticulated
      polyurethane.
AB  - Poly-N-para-vinylbenzyl-lactonamide (PVLA)-coated reticulated polyurethane (PVLA
      RPU) has been employed for the long-term maintenance of primary rat hepatocyte
      cultures. After 3 days of incubation of 2 x 10(7) hepatocytes/cm3 embedded in
      PVLA-RPU discs and kept in culture medium, most cells showed typical hepatocyte
      morphology, with some bile canaliculus-like intercellular spaces among the
      hepatocytes on examination with scanning and transmission electron microscopy.
      The cells were attached to the surface of the PVLA-RPU and formed multicellular
      spheroids in the reticulated pores. The hepatocytes maintained various liver
      specific functions such as albumin secretion, ammonium metabolism, urea synthesis
      and gluconeogenesis, and they were viable. The liver-specific functions could be
      maintained for more than 1 month when the cells were kept in the rats' peritoneal
      cavities. This new system may be useful as a bioreactor for an artificial liver.

PMID- 8138243
TI  - Enzyme inhibitory autoantibodies to pyruvate dehydrogenase complex in primary
      biliary cirrhosis differ for mammalian, yeast and bacterial enzymes: implications
      for molecular mimicry.
AB  - Primary biliary cirrhosis is a chronic autoimmune disease in which serum
      autoantibodies against the mitochondrial 2-oxo acid dehydrogenase enzyme
      complexes (M2 antibodies) are regularly present. Molecular mimicry of host
      proteins by bacterial counterparts is a suggested explanation for the origin of
      these autoantibodies. We tested this hypothesis by measuring the functional
      reactivity of serum autoantibodies by means of an enzyme inhibition assay against
      pyruvate dehydrogenase complex from different sources: mammalian, Saccharomyces
      cerevisiae and Escherichia coli. The 10 primary biliary cirrhosis sera all
      reacted on immunofluorescence study for M2 antibodies and on immunoblotting with
      the pyruvate dehydrogenase complex E2 subunit from each of the three enzymes, but
      there were strikingly different inhibitory capacities. The primary biliary
      cirrhosis sera were highly inhibitory for mammalian pyruvate dehydrogenase
      complex (10 of 10 inhibitory; mean level of inhibition, 99%), moderately
      inhibitory for yeast pyruvate dehydrogenase complex (10 of 10 inhibitory; mean
      level, 70%) and weakly inhibitory for Escherichia coli pyruvate dehydrogenase
      complex (4 of 10 inhibitory; mean level, 26%). Thus, with a functional assay that
      depends on epitope recognition of primary biliary cirrhosis sera, cross
      reactivity between mammalian and bacterial pyruvate dehydrogenase complex enzymes
      is low and molecular mimicry, at least at the B-lymphocyte level, is not
      supported.

PMID- 8138244
TI  - Stimulation of phagocytic activity of murine Kupffer cells by tuftsin.
AB  - Tuftsin (Thr-Lys-Pro-Arg) is a natural immunomodulating peptide. We have
      investigated for the presence of a specific tuftsin receptor on murine Kupffer
      cells using fluorescein-labeled tuftsin, which retains full biological activity.
      After incubation with fluorescein-labeled tuftsin, Kupffer cells displayed clear
      binding of this compound on the plasma membrane. Excess tuftsin inhibited this
      binding, indicating the presence of specific tuftsin receptors on the Kupffer
      cells. We then investigated the effect of tuftsin on the phagocytic activity of
      these cells. Phagocytosis assays were performed on 24-well plates between murine
      Kupffer cells and fluorescent microspheres. The greatest stimulatory effect of
      tuftsin on percent phagocytic cells over the control value was observed when the
      cells were incubated with particles at 1 microgram/ml tuftsin for 15 min at 37
      degrees C with a particle-to-Kupffer cell ratio of 50:1. Tuftsin also markedly
      increased the number of particles engulfed by Kupffer cells under the same
      conditions. These results indicate that Kupffer cells have specific tuftsin
      receptors; thus tuftsin can stimulate phagocytic activity of Kupffer cells, which
      constitute the majority of macrophages in the host and are situated strategically
      in the liver for host defense.

PMID- 8138245
TI  - Where does the gene for hemochromatosis lie in relation to HLA-A?

PMID- 8138246
TI  - Of mice, men and cholesterol.

PMID- 8138247
TI  - Bile duct obstruction by portal cavernoma.

PMID- 8138248
TI  - Biliary obstruction due to portal cavernoma.

PMID- 8138249
TI  - IASL Cancun Meeting. May 19-23, 1994. Abstracts.

PMID- 8138250
TI  - Hepatitis B virus subtypes and hepatitis C virus genotypes in patients with
      chronic liver disease in Nepal.
AB  - A total of 145 patients with chronic liver disease, including 20 with chronic
      hepatitis, 63 with cirrhosis and 62 with primary hepatocellular carcinoma from
      Nepal were tested for markers of hepatitis B virus or hepatitis C virus
      infection. HBsAg was detected in 57 (39%) and hepatitis C virus RNA in 12 (8%);
      the cause of liver disease was not known in the remaining 76 (52%). HBsAg was
      found in 5 (1.3%) of 379 normal controls, whereas hepatitis C virus-associated
      antibodies were detected in 13 (3.4%), none of whom was positive for serum
      hepatitis C virus RNA. Subtypes of 102 HBsAg samples, from patients and
      asymptomatic carriers, were adw in 35 (34%), adr in 4 (4%) and ayw in 48 (47%);
      the remaining 15 (15%) were of atypical subtypes such as ad, ay and a. Of 12
      hepatitis C virus RNA samples, genotype I was detected in 1, genotype II in 5 and
      genotype V in 1; the remaining five samples were not to be classified by
      polymerase chain reaction with primers specific for genotypes I to V deduced from
      hepatitis C virus core sequences, despite high hepatitis C virus RNA titers in
      all of them. Sequences of 192 amino acids in the entire E1 region of
      unclassifiable hepatitis C virus isolates from five patients differed from each
      other in 17% to 23%, and varied from reported isolates of defined genotypes in
      13% to 44%. These results indicate that atypical subtypes of hepatitis B virus
      and novel genotypes of hepatitis C virus would prevail in Nepal.

PMID- 8138251
TI  - High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in
      transgenic mice.
AB  - We studied the development of liver tumors in male HBx gene transgenic mice. Of
      two lineages studied, in the lineage with the lowest HBx gene expression liver
      tumors developed only in an incidence comparable with that in normal CD-1 strain,
      whereas 84% of male mice with a high level of the HBx gene product succumbed to
      liver neoplasia, indicating that continued HBx gene expression higher than a
      certain threshold level may be necessary for the development of hepatic
      neoplasia. Sixty-five mice from a lineage with a high level of HBx expression
      were then followed throughout their 24-mo lifespan. The livers of transgenic mice
      showed foci of cellular alteration with cytoplasmic vacuolations around the
      central veins from the age of 2 mo, but these foci did not expand progressively
      by the age of 12 mo. Immunostaining demonstrated such hepatocytes had higher
      expression of HBx protein than surrounding cells. Neoplastic lesions including
      liver cell adenomas and hepatocellular carcinomas developed from the age of 13
      mo. By bromodeoxyuridine labeling analysis, hepatocytes in altered foci were
      found to have increased DNA synthesis, whereas no labeling was observed in age-
      and sex-matched nontransgenic littermate controls. Furthermore, DNA content
      analysis revealed the existence of several small aneuploid peaks in the
      transgenic liver before the age of tumor development. These results suggest that
      the continued expression of HBx gene may initiate a complex process to
      hepatocellular carcinoma by inducing DNA synthesis and placing large numbers of
      hepatocytes subjective to secondary events for transformation.

PMID- 8138252
TI  - Interferon-alpha for chronic hepatitis C: an analysis of pretreatment clinical
      predictors of response.
AB  - To identify predictors of short-term and sustained ALT normalization after
      interferon treatment in adult patients with chronic hepatitis C, we performed a
      meta-analysis of individual patients' data, with construction and cross
      validation of a prediction rule, in 361 patients from two randomized trials. In
      one trial, 116 subjects with transfusion-related chronic hepatitis C were treated
      with lymphoblastoid interferon (5 MU/m2 three times a week for 2 mo, then 3 MU/m2
      three times a week for 4 or 10 mo). In the other study, 245 patients with
      community-acquired chronic hepatitis C received recombinant interferon-alpha 2b
      (10 MU three times a week for 2 mo, then 5 MU three times a week for 4 mo; then
      random allocation of subjects with normal aminotransferase levels to stop or
      continue interferon for a further 6 mo). Overall, 164 subjects (45%; 95%
      confidence interval, 40% to 50%) had short-term responses; 61 (18%; 95%
      confidence interval, 14% to 22%) maintained sustained responses. Sixty patients
      (17%; 95% confidence interval, 13% to 21%) withdrew from treatment because of
      side effects or subjective intolerance. Logistic regression analysis showed that
      short-term and sustained response were independently predicted by lobular
      structure on pretreatment liver biopsy (p < 0.0001) and by short disease
      duration, defined as the time elapsed since transfusion in posttransfusion cases
      or since the first observation of abnormal aminotransferase levels in cryptogenic
      disease (p < 0.01). Rules to predict short-term and sustained response to
      interferon were derived from these items, showing a discriminatory ability of
      0.73 and 0.70.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138253
TI  - Contribution of hepatitis C virus to non-A, non-B fulminant hepatitis in Japan.
AB  - To assess the contribution of hepatitis C virus to non-A, non-B fulminant
      hepatitis in Japan, we compared 10 major clinical features among 7 patients with
      type B fulminant hepatitis (type B group), 13 patients with non-A, non-B
      fulminant hepatitis with evidence of hepatitis C virus infection (type C group)
      and 10 patients without evidence of hepatitis C virus infection (NANB group).
      Duration from first symptom to coma and that from onset of jaundice to coma was
      significantly longer in the type C group (median = 39 and 25 days, respectively)
      and in the non-A, non-B group (median = 29 and 12 days, respectively) than in the
      type B group (median = 9 and 2 days, respectively) (p < 0.01). The maximum median
      AST level was significantly lower in the type C (1,689 U/L) and non-A, non-B
      groups (1,353 U/L) than in the type B group (5,780 U/L) (p < 0.05). Serum
      transaminase levels showed a single peak in six of seven of the type B patients,
      whereas they formed two or more peaks in all of the type C patients and in most
      of the non-A, non-B group (p < 0.05). Six of seven in the type B group, 6 of 13
      in the type C group and 4 of 10 in the non-A, non-B group survived (p < 0.05). We
      found no significant difference in any of the 10 clinical features between the
      type C and non-A, non-B groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138254
TI  - Multiple viral infection as the most common cause of fulminant and subfulminant
      viral hepatitis in an area endemic for hepatitis B: application and limitations
      of the polymerase chain reaction.
AB  - We tested serum samples from 25 fulminant hepatitis and 7 subfulminant hepatitis
      patients for hepatitis A, B, C, D and E viral markers and nucleic acids by means
      of polymerase chain reaction to determine the role of each virus on such
      catastrophic events in an area endemic for hepatitis B. Of these 32 patients, 14
      (44%) were hepatitis B virus carriers with hepatitis D virus superinfection (1
      with hepatitis C virus infection), 3 others had coexisting hepatitis B virus and
      hepatitis C virus infections, 6 had reactivation of underlying chronic hepatitis
      B, 4 had acute hepatitis B, 2 had acute hepatitis C and 1 had acute hepatitis E.
      Pathogenesis in the remaining two cases was unclear. Serum hepatitis B virus DNA
      was detectable in most carriers without superinfection and in one third of those
      with superinfection detected on polymerase chain reaction (6 of 7 vs. 6 of 16, p
      < 0.05). Of the polymerase chain reaction-positive samples, only 17% yielded
      positive results on spot hybridization. Hepatitis B virus DNA was the only marker
      to indicate coexisting hepatitis B virus infection in one patient positive for
      hepatitis C virus antibody. Only three of the six hepatitis C virus-infected
      cases were positive for hepatitis C virus antibody; diagnoses in the remaining
      three were established by means of detection of hepatitis C virus RNA. Of the
      hepatitis D virus-infected patients, infection in only half was diagnosed by
      means of total hepatitis D virus antibody assay. Twelve (86%) were positive for
      anti-hepatitis D virus IgM and nine (64%) had detectable hepatitis D virus RNA on
      reverse transcription-polymerase chain reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138255
TI  - Immunological disorders in C virus chronic active hepatitis: a prospective case
      control study.
AB  - Hepatitis C virus-related chronic hepatitis may be associated with various
      immunological disorders. The aim of this study was to determine prospectively the
      prevalence of the clinical, biochemical and pathological immunological
      abnormalities in a series of 61 consecutive patients with chronic hepatitis C,
      compared with those in 61 age- and sex-matched control subjects without markers
      of hepatitis C virus and hepatitis B virus infections and with those in 61
      patients with chronic hepatitis B. The following investigations were
      systematically performed before any treatment: detection of serum
      cryoglobulinemia and rheumatoid factor, detection of a large variety of serum
      anti-tissue antibodies, biopsy of labial salivary glands, ophthalmological
      examination, dosage of thyroid-stimulating hormone and in vivo capillary
      microscopy. Cryoglobulinemia was found in 36% of the hepatitis C virus patients,
      four of whom had dermatological and/or neurological manifestations of vasculitis,
      and rheumatoid factor was present in 70%. Serum anti-tissue antibodies were
      detected in 41% of cases, mostly antinuclear and anti-smooth muscle antibodies.
      Liver-kidney microsomal and antithyroid antibodies were rare. Salivary gland
      lesions were found in 49% of the patients: all had lymphocytic capillaritis,
      sometimes associated with lymphocytic sialadenitis resembling that of Sjogren's
      syndrome, but without features of sicca syndrome and Ro/SSA antibodies. Five
      percent of the patients had lichen planus. The prevalences of cryoglobulinemia,
      rheumatoid factor and anti-tissue antibodies were significantly higher than those
      in the control group and patients with chronic hepatitis B.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8138256
TI  - Decrease in serum levels of markers of hepatic connective tissue turnover during
      and after treatment of chronic hepatitis B with interferon-alpha.
AB  - Interferon-alpha induces remission in 30% to 40% of patients with chronic
      hepatitis B, but its effect on hepatic connective tissue turnover has not been
      well documented. We studied the changes in serum procollagen III propeptide and
      laminin-P1 peptide (Lam-P1) in 33 patients with chronic hepatitis B (11
      nontreated controls and 22 treated patients) during a 4-mo randomized trial of
      interferon-alpha. Liver biopsy specimens were obtained at the start of treatment
      and 12 mo later. Liver biochemical tests, procollagen III propeptide, laminin-P1
      peptide and hepatitis B virus DNA polymerase were determined before treatment
      with interferon was begun (mo -3), at the initiation (0 time) and completion of
      treatment (mo 4) and also at 8, 12 and 18 mo. Treated patients were classified as
      "responders" and "nonresponders" on the basis of clearance of HBV e antigen from
      serum. There were no significant changes in the control group, whereas the
      responders had persistent decreases in ALT, AST, hepatitis B virus dna
      polymerase, procollagen III propeptide and laminin-P1 peptide. The nonresponders
      had transient ALT, AST and hepatitis B virus dna polymerase reductions that
      returned toward baseline levels during follow-up, but procollagen III propeptide
      and laminin-P1 peptide persisted below the baseline at mo 18. Significant
      correlations between procollagen III propeptide and laminin-P1 peptide with ALT,
      AST and liver histologic specimens were noted at baseline but not after 12 mo.
      Changes in procollagen III propeptide levels also correlated with changes in AST,
      ALT and liver histologic specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138257
TI  - Strong transient expression of the type I interferon-induced MxA protein in
      hepatitis A but not in acute hepatitis B and C.
AB  - The human MxA protein is a new specific marker for type I interferon activity
      both in vitro and in vivo. In the study presented here, this interferon-induced
      marker, as well as the 2',5'-oligoadenylate synthetases, was measured in
      circulating mononuclear cells from 21 patients with acute hepatitis A, 20
      patients with acute hepatitis B and 14 patients with acute hepatitis C for
      determination of the activation of the interferon system in these viral diseases.
      In acute hepatitis A a strong expression (10 of 10 patients) of the MxA protein
      and the 2',5'-oligoadenylate synthetase activity in peripheral-blood mononuclear
      cells was observed during the first 2 wk after onset of clinical symptoms. In
      this period the MxA protein concentrations reached levels similar to those
      measured in patients treated with up to 5 x 10(6) IU interferon-alpha three times
      a week. Beyond wk 3, in eight of eight patients with hepatitis A no increased MxA
      protein levels were found. In contrast, peripheral-blood mononuclear cells from
      patients with acute hepatitis B contained either no measurable MxA protein or
      only slightly higher levels of the MxA protein, as did those of most patients (12
      of 14) with acute hepatitis C. The MxA protein levels of both hepatitis B and C
      patients were significantly lower (p < 0.05) than those found in hepatitis A
      patients. Furthermore, sera from 6 of 10 patients with hepatitis A, but none of
      10 patients with acute hepatitis B and C, contained measurable MxA protein. This
      serum MxA protein may originate from interferon-exposed and subsequently damaged
      liver cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138258
TI  - Seroprevalence of antibody to hepatitis E virus among Chinese subjects in Taiwan.
AB  - Recently, with an available serological hepatitis E virus diagnostic kit, the
      prevalence of IgG antibody to hepatitis E virus among Chinese subjects in Taiwan
      was evaluated by means of a solid-phase enzyme-linked immunoassay based on two
      recombinant hepatitis E virus antigens. The overall prevalence of hepatitis E
      virus antibody was 10.7% among 384 healthy subjects older than 20 yr but only
      0.3% among 600 schoolchildren and young adolescents younger than 20 yr (p <
      0.0001). Serial serum samples from 32 hepatitis E virus antibody-positive healthy
      subjects showed 84% of them to have antibodies persisting more than 3 to 8 yr.
      Among patients with viral hepatitis, IgG hepatitis E virus antibody was detected
      in 10% of 10 patients with acute hepatitis A, in 9.5% of 63 patients with acute
      hepatitis B and in 13.9% of 36 patients with acute posttransfusion hepatitis C.
      Of 77 patients with sporadic non-A, non-B hepatitis, IgG hepatitis E virus
      antibody was detected in 18.9% of 53 patients positive for antibody to hepatitis
      C virus and in 45.8% of 24 patients negative for hepatitis C virus antibody (p <
      0.03). Most of our hepatitis E virus antibody-positive normal subjects and
      patients had never been abroad. These findings demonstrate that sporadic or
      subclinical hepatitis E virus infections also exist among the Chinese subjects in
      Taiwan. Hepatitis E virus infection may play an important role in patients with
      hepatitis C virus antibody-negative sporadic non-A, non-B hepatitis. IgG
      hepatitis E virus antibody in the sera of normal subjects may last for more than
      8 yr.

PMID- 8138259
TI  - Serum hepatitis C virus RNA quantity and histological features of hepatitis C
      virus carriers with persistently normal ALT levels.
AB  - We studied hepatitis C virus carriers with normal liver function to evaluate the
      histological features of their livers and the replicative levels of hepatitis C
      virus. Liver biopsies were performed in 22 hepatitis C virus carriers with
      persistently normal ALT levels. Hepatitis C virus RNA in serum was quantified
      with a competitive assay that combined reverse transcription and the polymerase
      chain reaction, which is based on co-amplification of the target RNA with known
      amounts of synthetic mutated RNA. Three patients had normal livers on
      histological study, whereas the other 19 had chronic persistent hepatitis, with
      lymphoid infiltrates or aggregates in portal tracts commonly observed but
      intralobular inflammatory changes absent or minimal. The titer of hepatitis C
      virus RNA (logarithmic transformed copy number per milliliter of serum) varied
      from 4.0 to 8.0 (mean +/- S.D.: 6.3 +/- 1.1); it was significantly lower in the
      three patients with normal livers (4.3 +/- 0.2) than in those with chronic
      persistent hepatitis with mild (6.4 +/- 0.8, n = 11) or moderate (7.1 +/- 0.5, n
      = 8) portal inflammation. The titer of hepatitis C virus RNA was correlated with
      the total score (r = 0.68) and the score for portal inflammation (r = 0.68) in
      the histological activity index. These results indicated that there seem to be
      "healthy carriers" of hepatitis C virus with extremely low levels of viral
      replication. However, in most hepatitis C virus carriers with persistently normal
      ALT levels, there are inflammatory changes in the portal tracts, with severity
      depending on the replicative levels of hepatitis C virus.

PMID- 8138260
TI  - Inappropriate expression of blood group antigens in hepatic allografts.
AB  - We examined the expression of blood group antigens of the ABO, Lewis and Kell
      antigen systems using monoclonal antibodies and immunohistochemical study on 42
      liver allograft specimens from 33 patients who underwent liver transplantation
      between 1986 and 1991 to learn whether altered blood group antigen expression
      might have a bearing on the immunopathogenesis of transplant rejection. Specimens
      were obtained at intervals of 0 days to 3 yr after transplant; they yielded the
      following histological diagnoses; time zero (n = 4), acute rejection (n = 4),
      pure cholestasis (n = 4), biliary obstruction (n = 4), early chronic rejection (n
      = 4), end-stage chronic rejection (n = 15) and miscellaneous late posttransplant
      biopsies (n = 7). Aberrant expression of blood group antigens was observed in 5
      of 15 patients with chronic rejection. Two transplants into the same group O
      patient showed aberrant expression of AB antigens on hepatocytes, with a
      canalicular pattern, in group O-transplanted livers. In all three cases in which
      a group O liver was transplanted into a group A recipient and histological signs
      of chronic rejection were present, antibody staining showed acquisition of
      recipient blood phenotype by the donor liver bile ducts, endothelium or both.
      Aberrant expression of ABO antigens was seen only in chronic rejection. In seven
      cases we noted canalicular staining of periportal hepatocytes with the Lewis
      antibodies, normally confined to ducts and ductules. This was associated with
      severe cholestasis in six of the seven cases and may have represented early
      ductular metaplasia. These changes in carbohydrate cell surface phenotype may
      play a role in regulation of hepatic allograft susceptibility to immune-mediated
      damage.

PMID- 8138261
TI  - Short-term effects of simvastatin on bile acid synthesis and bile lipid secretion
      in human subjects.
AB  - To test whether de novo synthesis of cholesterol is a limiting factor for bile
      acid synthesis, we studied the acute effect of simvastatin, an inhibitor of HMG
      coenzyme A reductase (the limiting step of cholesterol synthesis) on bile acid
      synthesis and biliary lipid secretion in subjects with interrupted enterohepatic
      circulation. In these conditions bile acid synthesis is derepressed and is
      assumed to equal biliary bile acid secretion. Five cholecystectomized patients
      fitted with T-tubes were studied. All subjects were administered simvastatin (80
      mg as a single dose) 5 days after surgery. Bile was collected in 3-hr intervals
      for 15 hr before and 30 hr after the administration of the drug. During the
      experiment we kept the enterohepatic circulation of bile acid interrupted by
      inflating an occludable balloon inserted, during cholecystectomy, in the common
      bile duct. Simvastatin induced significant decreases of plasma total and low
      density lipoprotein cholesterol concentrations, from 163 +/- 29 mg/dl and 97 +/-
      24 mg/dl of the pretreatment value to 144 +/- 30 mg/dl and 82 +/- 22 mg/dl 18 hr
      after simvastatin administration, respectively. Bile flow tended to increase
      after simvastatin, and the mean values from the third to the 15th hour after
      simvastatin administration (22.1 +/- 1.9 ml/hr) were significantly greater than
      the mean values of the pretreatment period (19.9 +/- 2.8 ml/hr). Concomitantly
      biliary bile acid, cholesterol and phospholipid concentrations fell from basal
      values of 15.9 +/- 5.1, 2.3 +/- 0.3 and 5.5 +/- 0.3 mmol/L to mean values, after
      treatment, of 9.0 +/- 3.5, 1.9 +/- 0.5 and 3.0 +/- 0.9 mmol/L,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138262
TI  - Possible multicentric occurrence of hepatocellular carcinoma: a
      clinicopathological study.
AB  - To assess the features of multicentric occurrence in hepatocellular carcinoma, we
      analyzed 10 of 72 patients (14%) who had undergone hepatic resection for
      hepatocellular carcinoma from May 1989 to October 1992 both clinically and
      pathologically. The multicentric occurrence of hepatocellular carcinoma was
      defined among the simultaneously detected small tumors as (a) at least one tumor
      consisting of extremely well-differentiated (grade I) hepatocellular carcinoma
      growing in a replacing pattern or (b) one of a group of hepatocellular carcinomas
      growing in an area of adenomatous hyperplasia. Of the 10 patients, the tumors in
      9 were diagnosed as synchronous multicentric hepatocellular carcinomas, whereas
      the tumor in 1 was considered metachronous. All patients had cirrhosis; one of
      them had hepatitis B virus infection and nine patients had HCV infection. The
      inflammatory findings in the parenchyma were determined on the basis of serum
      enzyme values (AST, 89 +/- 27 IU/L; ALT, 96 +/- 43 IU/L). One or two tumors in 9
      of 10 patients had thin trabecular or trabecular patterns showing replacing
      growth. In addition, one of the two tumors in two of nine patients was observed
      growing in areas of adenomatous hyperplasia. Recurrences were found in 4 of 10
      patients. The 3-yr disease-free survival rate was 23%. Multiple recurrences were
      recognized in the two patients, and in the patients who underwent repeat surgery,
      grade I tumors were also found. Even though these tumors were small and well
      differentiated, the recurrence rate was high. Therefore to detect the recurrence
      of metachronous multicentric hepatocellular carcinoma at an earlier stage,
      careful follow-up after surgery should be carried out.

PMID- 8138263
TI  - Alpha-smooth muscle actin-positive perisinusoidal stromal cells in human
      hepatocellular carcinoma.
AB  - The purpose of this study is to clarify the morphological characteristics and
      functional significance of the perisinusoidal stromal cells in hepatocellular
      carcinoma. The liver specimens surgically resected from 24 patients with
      hepatocellular carcinoma were studied by electron microscopy and
      immunohistochemistry using monoclonal antibodies against alpha-smooth muscle
      actin, vimentin and desmin. In the tissue space between endothelial cells and
      trabeculae of cancer cells, the stromal cells were frequently found. They were
      strongly positive for alpha-smooth muscle actin, weakly and less frequently
      positive for vimentin but negative for desmin. They varied in shape, size and
      distribution, stretching cytoplasmic processes and occasionally surrounding the
      trabeculae of cancer cells. They contained considerable amounts of microfilaments
      that were positive for alpha-smooth muscle actin and condensed in cell periphery.
      Along the cell membrane, the short dense areas and pinocytotic vesicles were
      seen. The external lamina incompletely invested the stromal cells. They were
      always surrounded by amorphous material. In the granulation tissue and fibrotic
      areas around necrotic cancer tissue, they were increased in size and number. On
      the other hand, immunohistochemically and ultrastructurally, they closely
      resembled the Ito cells in the piecemeal necrosis that showed myofibroblastic
      transformation. These results suggest that the perisinusoidal stromal cells in
      nonnecrotic cancer tissue produce the extracellular matrix in the tissue space
      and maintain the cancerous trabecular structure. After necrosis of cancer tissue,
      they may become activated and actively participate in the fibrosis.

PMID- 8138264
TI  - Assessment of hepatic iron overload in thalassemic patients by magnetic resonance
      spectroscopy.
AB  - The transverse relaxation time of water protons is shortened by the presence of
      iron. This shortening depends on the amount and the environment of iron in the
      sample. We have developed a method for measuring short transverse relaxation time
      noninvasively by magnetic resonance spectroscopy. To evaluate magnetic resonance
      spectroscopy as a means of assessing hepatic iron content in patients with
      transfusional iron overload, we compared the results obtained with this method
      with those obtained by other means of assessing total body iron content. The
      correlation between the liver biopsy iron concentration and 1/transverse
      relaxation time was highly significant (r = 0.95, p < 0.004, n = 6) for iron
      loads up to 3% dry weight. The correlation between serum ferritin and
      1/transverse relaxation time was also significant, but the correlation
      coefficient was much lower (r = 0.67, p < 0.002, n = 20). The correlation between
      24-hr urinary iron excretion and 1/transverse relaxation time was not
      significant, nor was that between AST and 1/transverse relaxation time. We
      conclude that magnetic resonance spectroscopic determination of the transverse
      relaxation time of hepatic water is an accurate method of measuring liver iron
      content, especially when the iron content is below 3%. Because it is a
      noninvasive method that is associated with negligible side effects, it could
      provide clinicians with an excellent means of assessing the effectiveness of the
      various therapeutic strategies used in the management of patients with iron
      overload.

PMID- 8138265
TI  - Characteristics of hepatocellular carcinoma originating in the caudate lobe.
AB  - Nine patients with hepatocellular carcinoma originating in the caudate lobe who
      underwent hepatic resection were studied. The caudate lobe was divided into three
      parts, according to the criteria of Kumon, including the Spiegel lobe, the
      paracaval portion and the caudate process. The tumors were located in the Spiegel
      lobe in four, the paracaval portion in four and the caudate process in one.
      Surgical procedures consisted of right hepatic lobectomy in one, central
      bisegmentectomy in one and caudate lobectomy in seven. The mean surgical time was
      379 +/- 129 min; the mean estimated blood loss was 2,994 +/- 2,303 ml. The above
      mentioned surgical risks were more clearly recognized in the paracaval portion
      than in the Spiegel lobe. In addition, most patients experienced significant post
      operative complications. Six of eight patients with 6 mo or longer follow-up had
      recurrences, and two of six patients died. The characteristics of hepatocellular
      carcinoma in the caudate lobe were as follows: (a) a higher surgical risk, and
      more definite risk in the paracaval portion; and (b) a higher rate of early
      recurrence. A left lobectomy for the Spiegel lobe, a right or left
      trisegmentectomy for the paracaval portion and a right lobectomy for the caudate
      process would be ideal from the point of view of the portal supply of the caudate
      lobe. However, in cirrhotic patients either a caudate lobectomy or partial
      resection might be preferable because longer survival can be expected.

PMID- 8138266
TI  - Murine liver allograft transplantation: tolerance and donor cell chimerism.
AB  - Nonarterialized orthotopic liver transplantation with no immunosuppression was
      performed in 13 mouse-strain combinations. Two strain combinations with major
      histocompatibility complex class I and class II and minor histocompatibility
      complex disparity had 20% and 33% survival of more than 100 days, but the other
      11 combinations, including four that were fully allogeneic and all with only
      class I, class II or minor disparities, yielded 45% to 100% survival of more than
      100 days. Long-living recipients permanently accepted donor-strain heterotopic
      hearts transplanted on the same day or donor-strain skin 3 mo after liver
      transplantation, in spite of detectable antidonor in vitro activity with mixed
      lymphocyte reaction and cell-mediated lymphocytotoxicity testing (split
      tolerance). In further donor-specific experiments, liver grafts were not rejected
      by presensitized major histocompatibility complex class I-disparate recipients
      and they protected donor-strain skin grafts from second set (or any) rejection.
      Less frequently, liver transplantation rescued rejecting skin grafts placed 1 wk
      earlier in major histocompatibility complex class I, class II and minor
      histocompatibility complex, class II or minor histocompatibility complex
      disparate strain combinations. Donor-derived leukocyte migration to the central
      lymphoid organs occurred within 1 to 2 hr after liver transplantation in all
      animals examined, persisted in the surviving animals until they were killed (>
      375 days), and was demonstrated with double-immunolabeling to be multilineage.
      The relation of these findings to so-called hepatic tolerogenicity and to
      tolerance in general is discussed.

PMID- 8138267
TI  - Cyclosporine withdrawal for nephrotoxicity in liver transplant recipients does
      not result in sustained improvement in kidney function and causes cellular and
      ductopenic rejection.
AB  - Twelve consecutive liver transplant recipients with stable allograft function and
      cyclosporine nephrotoxicity were subjected to cyclosporine withdrawal in an
      attempt to halt and possibly reverse renal damage. Only patients who met the
      following criteria were included: (a) triple immunosuppression with cyclosporine,
      azathioprine and prednisone; (b) stable graft function for at least 1 yr without
      rejection; and (c) serum creatinine greater than 2.1 mg/dl or renal clearance
      less than 35 ml/min. Cyclosporine was reduced by 50 mg every 3 wk until
      discontinuation, prednisone was temporarily increased from 10 to 20 mg/day and
      azathioprine was maintained at 2 mg/kg/day. Sustained improvement in kidney
      function in the 12 patients was minimal, with the mean serum creatine level
      decreasing from 2.5 +/- 0.5 mg/dl (mean +/- S.D.) at study entry to 2.4 +/- 1.2
      mg/dl after a mean follow-up of 18 +/- 6 mo. In six patients, histologically
      confirmed cellular rejection developed after a mean of 5 +/- 6 mo from the time
      that cyclosporine withdrawal was begun. Two of six patients with rejection
      responded to bolus steroid therapy and are in stable condition at this writing
      with low-dose cyclosporine (2.8 and 3.2 mg/kg/day). Two patients initially
      responded to bolus steroids but later exhibited ductopenic rejection; one
      responded to treatment with FK 506 and the other died of sepsis. The two
      remaining patients were steroid unresponsive. One responded to treatment with
      OKT3 and is now stable on low-dose cyclosporine (2.3 mg/kg/day), but in the other
      ductopenic rejection developed and the patient died of sepsis during rescue
      therapy with FK 506.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138268
TI  - Hepatic lidocaine metabolism and liver histology in patients with chronic
      hepatitis and cirrhosis.
AB  - Recent advances in the medical and surgical treatment of chronic hepatitis and
      cirrhosis have made it increasingly important to develop noninvasive tests of
      liver function. Our study has evaluated the hepatic conversion of lidocaine to
      its primary metabolite monoethylglycinexylodide and compared this with liver
      histological findings in 225 patients with chronic hepatitis (161 with hepatitis
      C, 23 with hepatitis B, 21 with autoimmune hepatitis and 20 with cryptogenic
      hepatitis). One hundred seven (47.7%) patients had cirrhosis at the time of
      evaluation. A decline in monoethylglycinexylodide production was observed with
      worsening liver histological conditions from a mean of 81.5 +/- 7.0 ng/ml in
      patients with chronic persistent hepatitis to 61.2 +/- 5.5 ng/ml for chronic
      active hepatitis and 20.9 +/- 1.5 ng/ml in patients with cirrhosis (p < 0.05). A
      further stepwise decline in monoethylglycine xylodide production was observed
      with worsening Child class: from 25.5 +/- 2.2 ng/ml for class A patients to 8.9
      +/- 1.4 ng/ml for patients with Child class C disease (p < 0.05). All patients
      with monoethylglycinexylodide production less than 20 ng/ml had cirrhosis
      confirmed on histological examination. In contrast, no relationship was observed
      between liver histological status and serum transaminases (AST or ALT),
      bilirubin, albumin and prothrombin time. Thirty-five patients underwent repeat
      histological evaluation and monoethylglycinexylodide testing after receiving at
      least 6 mo treatment for chronic hepatitis (interferon for hepatitis B and C and
      corticosteroids for autoimmune hepatitis). The change in monoethylglycinexylodide
      production observed in these patients was a linear function of the change in
      Knodell histological index (r = 0.73, p < 0.005).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138269
TI  - Effects of different bile salts on steady-state mRNA levels and transcriptional
      activity of cholesterol 7 alpha-hydroxylase.
AB  - Cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the bile acid
      synthesis pathway, is down-regulated by taurocholate by way of negative feedback
      control at the level of gene transcription. The molecular basis of regulation of
      cholesterol 7 alpha-hydroxylase by other hydrophobic bile salts and under more
      physiological conditions is not known. The aim of this study was to investigate
      the molecular basis of regulation of cholesterol 7 alpha-hydroxylase by several
      naturally occurring bile salts in rats with intact enterohepatic circulation.
      Male Sprague-Dawley rats were pair-fed for 14 days normal chow (control),
      cholestyramine (5% of diet), cholic acid (1%), chenodeoxycholic acid (1%) or
      deoxycholic acid (0.25%). When rats were killed, livers were harvested and HMG
      CoA reductase specific activity and cholesterol 7 alpha-hydroxylase specific
      activities, steady-state mRNA levels and transcriptional activity were determined
      and compared with those of control rats fed normal chow. Compared with results in
      paired controls, cholestyramine feeding led to an approximate threefold increase
      in HMG-CoA reductase specific activity. Feeding of hydrophobic bile salts
      profoundly decreased the specific activity of HMG-CoA reductase. Cholestyramine
      led to a three-fold increase in cholesterol 7 alpha-hydroxylase specific
      activity, steady-state mRNA levels and gene transcriptional activity. The feeding
      of cholic (1%), chenodeoxycholic (1%) and deoxycholic acid (0.25%) led to
      significant decreases in cholesterol 7 alpha-hydroxylase specific activities
      (62%, 84% and 97%, respectively), steady-state mRNA levels (72%, 29% and 61%,
      respectively) and transcriptional activities (44%, 43% and 54%,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138270
TI  - Inhibition by perhexiline of oxidative phosphorylation and the beta-oxidation of
      fatty acids: possible role in pseudoalcoholic liver lesions.
AB  - In an attempt to better understand the mechanisms for pseudoalcoholic liver
      lesions in human beings, we determined the effects of perhexiline on
      mitochondrial functions in mice and rats. A first series of studies suggested
      that protonated perhexiline entered mouse mitochondria along the mitochondrial
      membrane potential. Release of a proton in the mitochondrial matrix led to
      uncoupling of oxidative phosphorylation, and accumulation of perhexiline
      inhibited complexes I and II of the respiratory chain, decreased ATP formation in
      vitro and decreased the mitochondrial beta-oxidation of long-, medium- and short
      chain fatty acids in vitro and in vivo in mice. In cultured rat hepatocytes,
      exposure for 24 hr to 25 mumol/L perhexiline markedly decreased hepatocellular
      ATP and cell viability. Exposure to 5 mumol/L perhexiline did not modify ATP and
      viability but decreased the beta-oxidation of palmitic acid uniformly labeled
      with carbon 14 by 38%, increased hepatocyte triglyceride levels by 98% and
      produced microvesicular steatosis after 72 hr of culture. We conclude that
      perhexiline is concentrated inside mitochondria, where it inhibits both oxidative
      phosphorylation and the mitochondrial beta-oxidation of fatty acids. These
      effects may contribute to the development of necrosis, steatosis and possibly
      certain other pseudoalcoholic liver lesions in human beings.

PMID- 8138271
TI  - Hepatocyte growth factor in transgenic mice: effects on hepatocyte growth, liver
      regeneration and gene expression.
AB  - Attention has recently been focused on hepatocyte growth factor as a major
      candidate factor in liver regeneration because it is the most potent known
      mitogen for hepatocytes in vitro. However, hepatocyte growth factor also displays
      diverse activities in vitro as scatter factor, as an epithelial morphogen, as a
      pluripotent mitogen and as a growth inhibitor. Consequently, we developed
      transgenic mice that expressed hepatocyte growth factor under the control of
      albumin regulatory sequences to examine its in vivo role in hepatocyte growth.
      Hepatocytes of these mice expressed increased levels of hepatocyte growth factor
      as an autocrine growth factor. Hepatocyte growth factor was a potent stimulus for
      liver repair; the livers of hepatocyte growth factor-transgenic mice recovered
      completely in half the time needed for their normal siblings after partial
      hepatectomy. This transgenic model also enabled us to study the chronic effects
      of hepatocyte growth factor expression. During several months of observation, the
      labeling index of hepatocytes in albumin-hepatocyte growth factor mice was
      doubled, and liver DNA content was increased compared with that in wild-type
      mice. To identify intermediate signaling pathways for hepatocyte growth factor
      that might regulate this increased growth response, we examined transgenic mice
      for changes in expression of genes that are known to be regulated during liver
      regeneration. We found that levels of c-myc and c-jun mRNA were increased in the
      hepatocyte growth factor-transgenic mice. In additional experiments the increased
      c-myc expression was the consequence of increased transcription rates as seen in
      nuclear run-on and myc-CAT reporter gene experiments. We conclude that hepatocyte
      growth factor increases growth and repair processes when expressed for long
      periods in the liver and that c-myc and c-jun may be important intermediaries in
      the hepatocyte growth response caused by hepatocyte growth factor.

PMID- 8138272
TI  - Contribution of complement-stimulated hepatic macrophages and neutrophils to
      endotoxin-induced liver injury in rats.
AB  - The role of complement as potential activator for tissue macrophages and
      neutrophils was investigated in an experimental model of endotoxin-induced liver
      injury in male Fischer rats. Injection of Salmonella enteritidis endotoxin (1
      mg/kg) into Corynebacterium parvum-pretreated animals (7 mg/kg; single dose 6
      days before endotoxin) resulted in severe oxidant stress, as indicated by a 37
      fold increase of plasma levels of glutathione disulfide (basal concentration,
      0.36 +/- 14 mumol/L), accumulation of neutrophils in the liver (600 +/- 31
      neutrophils/50 high-power fields) and liver injury (plasma ALT, 1184 +/- 185 U/l;
      necrosis; 19% +/- 3%) 10 hr after endotoxin. The oxidant stress induced by 1
      mg/kg endotoxin in the C. parvum-treated animals was always significantly higher
      than that in control animals receiving the same dose of endotoxin. Inhibition of
      complement activation with the soluble complement receptor type 1 attenuated the
      oxidant stress and liver injury by 50% to 65% but had no effect on hepatic
      neutrophil accumulation or plasma tumor necrosis factor-alpha levels. Treatment
      with a monoclonal antibody directed against the alpha-chain of CD11b/CD18
      adhesion proteins (clone 17), which was highly effective in attenuating ischemia
      reperfusion injury in the liver by reducing the number of neutrophils and
      functionally inactivating these cells, neither protected against parenchymal cell
      injury nor affected hepatic neutrophil infiltration in the C. parvum model. We
      conclude that reactive oxygen derived from complement-stimulated macrophages is
      critical for the development of liver injury in the C. parvum/endotoxin model.

PMID- 8138273
TI  - The role of major histocompatibility complex and non-major histocompatibility
      complex encoded antigens in generation of bile duct lesions during hepatic graft
      vs.-host responses mediated by helper or cytotoxic T cells.
AB  - In these studies, we examined the role of discrete classes of alloantigen
      differences in generating nonsuppurative cholangitis during graft-vs.-host
      disease. Transfer of C57BL/6J (B6) splenocytes to class I major
      histocompatibility complex-disparate bm1 x B6 F1, class II major
      histocompatibility complex-disparate B6 x bm12 F1, or multiple non-major
      histocompatibility complex antigen-disparate Balb,B x B6 F1 mice led to the
      development of periportal inflammatory infiltrates and lymphocyte invasion of
      bile duct walls. However, frank destruction of bile duct walls was observed only
      in strain combinations with class I major histocompatibility complex or multiple
      non-major histocompatibility complex-encoded disparities. The concomitant
      presence of class II major histocompatibility complex differences and class I
      major histocompatibility complex or multiple non-major histocompatibility complex
      differences did not increase and in some cases was associated with less severe
      bile duct disease than was observed in strain combinations with discrete
      histocompatibility antigen differences. Depletion of L-leucyl-L-leucine methyl
      ester-sensitive cytotoxic T lymphocytes from donor inocula reduced the incidence
      of destructive bile duct lesions observed early in the course of graft-vs.-host
      disease in B6-->Balb.B x B6 F1 or B6-->bm1 x B6 F1 mice. However, transfer of CD8
      negative, L-leucyl-L-leucine methyl ester-resistant T helper cells alone was
      sufficient to generate destructive cholangitis in class I+II major
      histocompatibility complex-disparate or multiple non-major histocompatibility
      complex antigen-disparate strain combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138274
TI  - Transesophageal echocardiography.
AB  - TEE is the most recent and significant addition to the already existent array of
      cardiovascular ultrasound imaging techniques. Never before have cardiologists
      reaped so many benefits from their exploitation of the close anatomic
      relationship between the heart and esophagus, and never before has there been
      such a close co-operation and imparting of expertise between gastroenterologists
      and cardiologist. TEE consists of two-dimensional cardiac and vascular imaging
      via the esophagus by a flexible echoscope which contains a phased-array mono- or
      biplane transducer (5MHz) mounted on its distal end. It completely bypasses the
      transthoracic acoustic impedance and thereby provides superior resolution. TEE
      requires training of a cardiologist by a gastroenterologist in safe insertion and
      handling of the echoscope necessary for imaging. The indications and
      contraindications of TEE have been quickly defined in view of the past TTE and
      upper gastrointestinal endoscopic experience (ref. Tables 1 and 2). Our own and
      others experience indicate that only 8%-10% of the indicated TTE studies require
      supplementary TEE studies either because of inadequate or nondiagnostic TTE
      imaging for various technical reasons -- e.g., obesity, hyperinflation of lungs,
      thoracic age abnormalities such as severe pectus excavatum or kyphoscoliosis-or
      difficult areas of imaging such as left atrial appendage or interatrial septum in
      the sinus venosus region, aortic dissection, prosthetic valve dysfunction,
      valvular vegetation, complex congenital heart disease etc. One area in which TEE
      has made a significant impact is in the intraoperative and perioperative cardiac
      monitoring for left ventricular function during CABG, repair of intracardiac
      shunt, cardiac valve repair or replacement and complete removal of intracardiac
      air before discontinuation of cardiopulmonary bypass. In these contexts, TEE has
      also proved more practical, convenient and superior to TTE. TEE has also improved
      the imaging and problem solving in critical care units, particularly in those
      patients who have recently undergone cardiothoracic surgery and those who are on
      mechanical ventilation, traditionally the two clinical situations where TTE
      provides suboptimal results. TEE can safely be performed at the patient's bedside
      in these units. Refinement and miniaturizing of the transesophageal echoscope
      (5MHz, small, 6 to 8-mm circumference) has made it possible to perform TEE in
      infants and young children and improve the diagnosis and surgical management of
      both cyanotic and acyanotic congenital heart disease.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8138275
TI  - Progression and regression of coronary atherosclerosis.

PMID- 8138276
TI  - Distribution of cholesterol in HDL and its subfractions in patients with coronary
      atherosclerotic heart disease.
AB  - The distribution of HDL-C and its subclasses HDL3-C and HDL2-C and other serum
      lipids was studied in patients with coronary atherosclerotic heart disease
      grouped as young males (group 1) and older males (group 2) along with age matched
      controls. All the patients had significantly higher levels of serum cholesterol,
      triglycerides, LDL-C and VLDL-C and lower levels of HDL-C. The analysis of HDL -
      subclasses clearly demonstrated that the low levels of HDL-C was due to the
      significant decrease of cholesterol in both HDL3 (group 1: 32%; group 2: 30%) and
      HDL2 subclasses (group 1: 55%; group 2: 48%) compared to the respective control
      values. Further it has also been observed that this low level of HDL-C is a
      characteristic feature of patients irrespective of whether the levels of serum
      cholesterol and triglycerides are high or normal. Although both the HDL
      subclasses were decreased, the percentage of reduction of cholesterol was greater
      in the HDL2 than in HDL3 subclass. In addition, the levels of cholesterol either
      in HDL or any of its subclasses, HDL3 and HDL2 did not show any change in
      relation to the extent of coronary disease which was assessed by coronary
      angiography. This study confirms the inverse relation of HDL-C with coronary
      atherosclerosis and also indicates that, of all the lipid parameters examined,
      only HDL-C, particularly its subclass HDL2-C, shows independent inverse relation
      to the incidence of coronary atherosclerotic artery disease in men.

PMID- 8138277
TI  - Risk markers for ischaemic heart disease in South Asians.

PMID- 8138278
TI  - Early experience in the surgical treatment of the univentricular heart.
AB  - Eighteen patients under went surgical treatment of univentricular hearts between
      April 1989 till October 1992. All 18 had palliative operations in the form of: a
      modified Blalock-Taussig shunt (5), pulmonary artery banding (2), bidirectional
      Glenn shunts (2), conventional Fontan repair (1) and total cavo pulmonary
      connection (8). There were 11 males and 7 females. The mean age at operation was
      4.5 years (range, 1 month to 24 years). The average weight at operation was 12.2
      kg (range 2 to 43 kg). Associated anomalies included: transposition of the great
      arteries (4), pulmonary stenosis (9), pulmonary atresia (1), mitral atresia (1),
      atrioventricular septal defect (1) and patent ductus arteriosus (3). There were
      no intra operative deaths. There were 5 early deaths (27.7%). Causes of death
      were due to: blockage of a modified Blalock-Taussig shunt (1), respiratory
      failure (1), persistent ventricular arrhythmias (1) and low output syndrome (2).
      Treatment in the form of a systemic to pulmonary arterial shunt or an operation
      based on the Fontan principle may offer an initial palliative or definitive
      correction for this condition.

PMID- 8138279
TI  - Left ventricular aneurysm following surgical mitral commissurotomy: implications
      for balloon valvotomy.

PMID- 8138280
TI  - Transcatheter embolization of a coronary artery fistula.
AB  - A coronary artery fistula from left anterior descending coronary artery to right
      ventricle was successfully occluded by transcatheter embolization using steel
      coils. Transcatheter embolization seems to be the treatment of choice for
      coronary artery fistulas.

PMID- 8138281
TI  - Massive aneurysm of the thoracic aorta in an infant--a forme fruste of infantile
      Marfan syndrome.

PMID- 8138283
TI  - Guidelines for percutaneous transluminal coronary angioplasty. National PTCA
      Registry of India.

PMID- 8138282
TI  - Hypereosinophilic syndrome in a young child presenting as right ventricular mural
      thrombus.

PMID- 8138284
TI  - Blindness control in India--need for a multifaceted approach.

PMID- 8138285
TI  - Sexually transmitted diseases control programme in India: a public health
      approach.

PMID- 8138286
TI  - Value of Mantoux Test in diagnosis of tuberculosis in chronic illness.
AB  - Total 240 cases of 2-12 years age group who had contact of tuberculosis
      indirectly or directly and had chronic illness were screened for tuberculosis.
      Out of 240 cases, 180 cases were diagnosed as tuberculosis. Special emphasis was
      given on Mantoux Test (M.T.), though the battery of tests were done to diagnose
      tuberculosis. Out of 180 cases of Tuberculosis, M.T. was Positive in 97 cases
      (40.41%) and repeat M.T. was done after 3 weeks and was converted to Positive in
      20 cases (8.33%). Thus only M.T. help in diagnosis of Tuberculosis in almost 50%
      of the cases.

PMID- 8138287
TI  - Pulmonary function tests--a comparison between urban industrial and rural
      agricultural workers of Andhra Pradesh.
AB  - Physical parameters and pulmonary function tests (VC, FEV1, FEV1% and FEF25-75%)
      were collected in 112 urban industrial workers and 104 rural agricultural
      workers. These average values, values according to age and smoking habits were
      compared between urban and rural workers. Inspite of no differences in age, rural
      workers average height, weight, BSA is significantly lower than urban workers. A
      significant increase in VC value to the extent of 0.22 lit (7.1%), significantly
      lower FEV 1% value by 4.7% and reduce FEF25-75% value (4.7%) is demonstrated in
      rural than urban workers. Smoking is shown to produce airway obstruction in both
      urban and rural workers. A wide variation of PFT values between the present
      workers and other reported values in India is observed. This study indicates
      rural workers have better pulmonary capacity and less flow rates than their urban
      counterpart.

PMID- 8138288
TI  - Socioeconomic factors and prevalence of endemic goitre.
AB  - The present study was conducted on 2611 school children of a rural area of
      Meerut, with the objectives to find out the prevalence and distribution of
      endemic goitre and the socioeconomic variables associated with the distribution
      of the endemic goitre. Grading of goitre was done as per the criteria laid down
      by the WHO-1979 (1). The overall prevalence rate of endemic goitre was 50.1%, the
      prevalence was more among females (55.1%) as compared to males (47.2%). Maximum
      number of goitre cases were having grade Ia enlargement (46.9%) followed by grade
      Ib (34.1%), grade 2(15.0%) and grade 3 (4.0%). Prevalence increased with increase
      in age. Statistically significant differences were found in the prevalence of
      endemic goitre in relation to different religions and caste groups, different
      occupations of the parents/guardians of children and types of houses used for the
      purpose of living.

PMID- 8138289
TI  - Detection of antibodies to HIV-infection among high risk groups in Bihar (India).
AB  - Total of 4567 sera samples obtained from high risk groups viz. blood donors,
      patients attending skin/VD clinics have been examined for HIV-antibodies. None of
      them showed seropositivity. Since in Bihar, interaction with foreigners is not
      common as it is in the metropolitan cities of India, this may be one of the chief
      reasons for not finding any HIV-seropositive case so far. 7% of blood donors
      showed VDRL positive reaction. Both competitive ELISA and particulate
      agglutination tests on 375 sera samples gave identical negative result.

PMID- 8138290
TI  - Susceptibility status of Culex quinquefasciatus in Patna to insecticides.
AB  - To obtain the base line data, a study conducted in district Patna, Bihar to note
      the susceptibility status of adult Culex quinquefasciatus against organochlorine,
      organophosphorous and synthetic pyrethroids. It was found that adult of
      Cx.quinquefasciatus developed double resistance to DDT and dieldrin but
      susceptible to O.P. compounds and pyrethroids. Cx.quinquefasciatus larvae are
      also found susceptible to O.P compounds like malathion, temophos, fenthion and
      fenitrothion.

PMID- 8138291
TI  - Study of infant and childhood mortality in an ICDS block of eastern U.P.
AB  - Information on births and deaths was collected in 11 randomly selected AWW areas
      of Barhaj Mahen ICDS project area in Eastern U.P. by an independent survey team
      in 1988-89. The findings revealed that the births and deaths were under-reported
      to the tune of 36.6 and 13.9 percent respectively, by AWWs. The different
      demographic indicators generated from the data were as follows, CBR and CDR were
      30.3 and 7.1 per 1000 population. Neonatal mortality rate, IMR, and MMR were
      58.3, 74.7 and 6.5 per 1000 live births. 0-6 yr mortality was 16.3 per 1000
      children and constituted 37.5% of the total deaths. ARI, diarrhoea and fever were
      the major causes of mortality in 0-6 yr old children accounting for 25.9, 22.3
      and 14.8% respectively. The findings indicated that there was underreporting in
      adult mortalities despite the independent investigation, and a reduction in
      infant and childhood mortality possibly due to the beneficial effect of ICDS
      services.

PMID- 8138292
TI  - Fracture-dislocation of the thoracic spine without neurological lesion.

PMID- 8138293
TI  - Obturator hip dislocation with subcapital fracture of the femoral neck.

PMID- 8138294
TI  - Nail gun injury: an update.

PMID- 8138295
TI  - Successful resuscitation from suicidal hanging: report of three cases.
AB  - Three cases of successful resuscitation after attempted suicide by hanging are
      described. Although all came in with profound unconsciousness, they made a full
      recovery with no residual dysfunction after resuscitation by intubation and
      ventilation for 12 h. Steroids and mannitol were not used. All patients were
      referred for psychiatric consultation before discharge from hospital.

PMID- 8138296
TI  - Coracoid process and greater tuberosity fracture in unreduced shoulder
      dislocation.

PMID- 8138297
TI  - Squamous cell carcinoma arising in a traumatically induced epidermal cyst.

PMID- 8138298
TI  - Cutaneous leakage of cerebrospinal fluid following a stab wound to the back.

PMID- 8138299
TI  - Pneumocephalus: a hazard of pipe smoking.

PMID- 8138300
TI  - Bone necrosis of the femoral head after thoracic trauma.

PMID- 8138301
TI  - Small bowel entrapment in a pubic ramus fracture: a cautionary tale.

PMID- 8138302
TI  - Surgical management of major thoracic injuries.
AB  - Major thoracic injuries are uncommon in the United Kingdom and wide experience of
      their management by centres in this country has not been reported. Between 1985
      and 1990, 23 patients have undergone urgent thoracotomy at Birmingham Accident
      Hospital for suspected intrathoracic injury. The majority of these injuries were
      caused by penetrating trauma (13 patients). The commonest indications for
      thoracotomy were suspected intrathoracic haemorrhage in 13 patients and suspected
      cardiac tamponade in four patients. In three of the four patients with suspected
      cardiac tamponade, the diagnosis was correct, the tamponade successfully relieved
      together with repair of the lesion, and all three patients survived. Of the 13
      patients with intrathoracic haemorrhage, 10 survived after control of haemorrhage
      and repair of the lesion but three died: one from uncontrollable haemorrhage from
      a right middle lobe vessel laceration, one from associated multiple injuries and
      one from post-operative complications. The TRISS methodology was applied to audit
      our results. Two patients who died after a penetrating injury had a greater than
      50 per cent probability of death by the TRISS method. Two patients who died after
      a blunt injury had a less than 50 per cent probability of death by the TRISS
      method although one of these patients died from postoperative complications. This
      series illustrates the point that prompt recognition of a suspected intrathoracic
      injury and appropriate urgent surgical intervention to relieve cardiac tamponade
      and control intrathoracic haemorrhage in these patients can produce a successful
      outcome. In addition it it is essential that all units audit their own results in
      order to highlight areas where improvements in trauma care can be made.

PMID- 8138303
TI  - The significance of patient appearance in predicting severity of injury.
AB  - The observations of pallor, sweating, agitation and restlessness, at the time of
      an injured patient's admission to the resuscitation room, were compared with
      other more complex indices of injury severity and the ability of each observation
      to predict mortality was observed. The number of positive observations was
      significantly related to the Revised Trauma Score and the Injury Severity Score,
      and pallor was significantly related to mortality. The observation that an
      injured patient is pale is an important index of severity.

PMID- 8138304
TI  - The role of early flap coverage in the management of open fractures of both bones
      of the leg.
AB  - Sixty patients with type III injuries (open fractures) of the tibia were treated
      in a prospective fashion by combined orthopaedic and plastic surgical schemes
      based on the principles of early radical cleaning, a second-look operation, and
      early coverage of soft tissue defects with an appropriate local or distant flap.
      Stabilization of fractures was achieved by external fixation in most cases and
      patients were allowed to walk within 4-8 weeks (partial weight bearing). Bony
      union was achieved in 23.4 weeks. The mean hospital stay was 3.5 weeks. Limb
      salvage was achieved in all cases and there were no major complications.

PMID- 8138305
TI  - 1000 femoral neck fractures: the effect of pre-injury mobility and surgical
      experience on outcome.
AB  - This prospective study of 1000 femoral neck fractures (476 intertrochanteric and
      524 subcapital) found the pre-injury mobility to be the most significant
      determinant for post-operative survival. The intrahospital mortality of the 975
      surgically treated fractures was 11.3 per cent. Non-operatively treated fractures
      had a mortality of 60 per cent. The best predictors of morbidity and discharge
      mobility were age and pre-injury mobility. Delay was significant in the
      development of morbidity but only after 30 h from admission. Internal fixation
      produced a lower mortality than uncemented hemiarthroplasty. The use of acrylic
      cement was associated with an increased morbidity and mortality rate in
      hemiarthroplasties. Neither the grade nor the experience of the operating surgeon
      had an effect on mortality or morbidity.

PMID- 8138306
TI  - The scud missile disaster in Al-Khobar, Saudi Arabia, 1991: the orthopaedic
      experience.
AB  - The orthopaedic experience of the scud missile disaster in Al-Khobar, Saudi
      Arabia during the Gulf war is reviewed. This was by far the most severe of 70
      scud attacks. The majority of casualties had 'orthopaedic' injuries, fractures
      and soft tissue lacerations of the extremities and the back. Our experience
      confirmed the importance of the principles of planning triage beforehand and open
      wound treatment with secondary suture. Repeated ward rounds with reassessment of
      the patients proved beneficial. The ready availability of hospital beds in high
      risk situations of regional war highly facilitated the management of mass
      casualties.

PMID- 8138307
TI  - Proximal femoral fractures: a biomechanical study to compare intramedullary and
      extramedullary fixation.
AB  - This study assesses the rigidity and strength of fixation provided by
      intramedullary and extramedullary devices for proximal femoral fractures. Stable
      and unstable intertrochanteric fractures were studied in paired femora after
      internal fixation with the Gamma nail and Richards 135 degrees classic hip-screw
      implants; in subtrochanteric fractures, the 95 degrees Richards condylar screw
      was studied in addition. Subsidence of the sliding screw within the plate and
      nail constructs was measured. Fixation of subtrochanteric fractures with the
      intramedullary Gamma nail was significantly stronger and more rigid than that
      with the extramedullary screw plate devices. Under conditions of simulated
      protected weight bearing, the 95 degrees condylar screw plate provided more rigid
      fixation than did the 135 degrees hip screw. There was no significant difference
      in the strength of fixation of stable and unstable intertrochanteric fractures
      between the Gamma nail and the hip screw, although the Gamma nail provided more
      rigid fixation.

PMID- 8138309
TI  - Repair versus replacement of failed restorations.
AB  - Detailed criteria are needed to establish what constitutes failures which call
      for replacement or repair of restorations. Many factors play a role in the
      selection of repair as an alternative to replacement of failed restorations,
      including the clinical condition, the restorative material involved, and
      cost/benefit assessments. The advantages of repair of localised defects include
      saving of tooth structure and increased longevity of restorations at a low cost.

PMID- 8138308
TI  - Advances in portable and mobile equipment systems.
AB  - Specific efforts need to be directed towards eliminating and/or minimising the
      significant barriers that threaten the oral health of nursing home and homebound
      individuals. Exciting new portable dental system options are now available which
      will help to overcome difficulties associated with meeting the dental needs of
      this cohort.

PMID- 8138310
TI  - Current role of pharmaceuticals in prevention of caries and periodontal disease.
AB  - Epidemiological studies, based on the tooth surface as a unit of reference,
      confirm a strong correlation between dental plaque and the initiation of dental
      caries and periodontal disease. Therefore, prevention of caries and periodontal
      disease must be based on plaque control. Dental plaque can be controlled both
      mechanically and chemically. Both methods can be achieved by self-care, or
      professionally by dentists and dental hygienists. Chemical antimicrobial products
      are used for non-specific plaque control, as well as against specific microbes
      associated with the aetiology of caries and periodontal disease. Most products
      are applied topically (mouthrinses, gels, dentifrices and varnishes). The use of
      fluoride is generally accepted specifically for caries prevention. It is evident
      that the caries preventive effects of fluorides are mainly post-eruptive due to
      fluoride in drinking water, milk, salt and tablets. Dentifrices are the major,
      most widespread commercial product for topical use, followed by mouthrinses,
      gels, prophy pastes and slow-release fluoride products such as varnishes and
      glass ionomers. Dentifrices, mouthrinses and gels containing both fluorides and
      antimicrobial agents are also available. Products, methods and programmes for all
      individuals and selected risk individuals are discussed.

PMID- 8138311
TI  - Preventive goals in oral implantology.
AB  - Preventive dentistry is mainly concerned with caries and periodontal disease and
      little or no attention is paid to the prevention of alveolar bone loss. An
      overdenture contributes to the preservation of alveolar bone and offers a number
      of advantages in comparison to a conventional complete denture. After tooth
      extraction the atrophy of edentulous lower jaws can be prevented or delayed by
      using implants supporting an overdenture or a fixed mandibular prosthesis.
      Hydroxyapatite implants have been studied as submerged tooth root substitutes and
      have proven to be able to preserve the bulk of the alveolar ridge. A drawback of
      this submucosal implant is that the ridge maintenance depends solely on the
      physical presence of the hydroxyapatite implants. If implants support an
      overdenture or a fixed prosthesis they also play a role in maintaining the
      function of the bone in the different stages of reduction of the mandible. In
      this paper a classification for the different resorption stages of the mandible
      is presented and is used to determine the correct moment for preventive
      implantology. In addition the use of a lingualised occlusion is discussed as a
      contribution to the preventive goals in oral implantology.

PMID- 8138312
TI  - Bond strength testing--what does it mean?
AB  - In this paper, bond strength and various important factors in bond strength
      testing are discussed as well as the limitations in the interpretation and
      clinical relevance of such tests. Standardisation of bond strength testing is
      needed, and the solutions found in the new ISO document, ISO CD TR 11405 Dental
      Materials--Guidance on testing of adhesion to tooth structure, are referred to.
      Tensile and shear test methods are discussed and the bond strength values
      obtained with these methods compared. The influence of dentine substrate
      variations, such as remaining dentine thickness and surface treatment or removal
      of smear layer, are discussed as well as the storage conditions of specimens for
      in vitro tests, that is, short term, long term and thermocycling, and their
      relevance to the clinical situation. The information obtained from microscopical
      studies of fractured surfaces indicates that some adhesives may, under optimal
      conditions, obtain a bond strength sufficient to fracture the dentine.

PMID- 8138313
TI  - Contemporary use of agents in the control of progressive periodontitis.
AB  - Mechanical treatment of periodontitis is effective in most cases. However, there
      are cases which respond poorly and in which chemotherapy may be appropriate.
      Topical antibacterials applied supragingivally have limited or no effect upon
      established periodontitis caused by subgingival plaque. Subgingival application
      of antibacterial agents have in some studies shown a certain effect upon the
      inflammatory response particularly when applied in addition to conventional
      mechanical treatment. Long term results are not convincing. Speculation that some
      forms of periodontitis may be regarded as specific infections have led to the use
      of antibiotics in the treatment of such conditions. The drugs most often
      recommended are tetracyclines and imidazoles, and there are reports indicating
      arrest or retardation of further disease progression when they are applied as an
      adjunct to conventional mechanical treatment. Recently, local application of
      antibiotics in slow release devices has been claimed to be effective in combating
      periodontitis. Data presented so far have mostly shown reduced inflammation,
      while the effect upon the progression of the disease remains largely unknown.
      There seems to be general agreement that use of antibiotics in some cases of
      periodontitis is advantageous, but only if it is used as an adjunct to scaling
      and root planing.

PMID- 8138314
TI  - Improving utilisation of dental services by understanding cultural difference.
AB  - There is considerable health and medical research and anecdotal evidence showing
      that members of different cultural groups and people from lower socio-economic
      status and/or disadvantaged ethnic minority groups are prone to increased
      morbidity and early mortality. It is also clear that similar patterns are found
      in terms of dental health status and dental health morbidity. New Zealand data
      from the Second International Collaborative Study (ICSII) clearly illustrate that
      poorer health status overall and poorer dental health status are experienced by
      certain sections and groups within the population. Data from these studies
      suggest that members of lower socio-economic status groups, different ethnic
      groups and those with different cultural affiliations experience different health
      status and use the health services at differential rates. Some of the factors
      that appear to influence this are clearly related to cultural beliefs and
      attitudes. Future efforts by the New Zealand health services and in particular by
      the New Zealand dental health services to redress the situation need to be based
      on a clear understanding of the many factors that limit the availability and
      uptake of preventive and dental health care services by high risk groups.
      Understanding cultural difference is a key requirement.

PMID- 8138315
TI  - Technological advances in the clinical diagnosis of periodontal diseases.
AB  - Traditional diagnostic procedures for periodontal disease, such as probing and
      radiographic assessment, supply information on previous disease experience but
      not of present site-specific activity nor of possible future attachment loss.
      Although the newer automatic probes which record data electronically give higher
      resolution and accuracy than their manual counterparts, their use in clinical
      practice is only of value in longitudinal clinical trials. In general clinical
      practice, manual probing is adequate provided probing technique and probe tine
      characteristics are within acceptable limits. It is suggested that the general
      practitioner could use the CPITN method for screening purposes because of its
      relative speed and ease. This must, however, be supplemented by comprehensive
      probing in each sextant with advanced disease. The humble bitewing radiograph is
      likewise adequate for the assessment of alveolar bone loss in normal clinical
      practice but if refined data of bone loss over time is required, subtraction
      radiography is recommended. Currently, other forms of imaging technology have
      limited value in clinical practice because of technical complexity, access and
      cost. A number of other electronic devices are available which make the accurate
      assessment of mobility and occlusal function possible but, because the
      relationship between these signs and periodontitis is still equivocal, the
      general use of such apparatus is not indicated. The advent of a battery of easily
      performed chairside tests shows considerable promise for the future, particularly
      those tests that are becoming commercially available for the assay of host and
      bacterial markers of site-specific disease in the crevicular fluid. The clinical
      value and the cost-benefit of these assays need further investigation before they
      can be recommended for general use. Clinical practice objectives differ from
      those required for research projects and therefore the required sensitivity,
      specificity and predictive value of diagnostic tests must be in keeping with the
      intended purpose to justify the cost involved.

PMID- 8138316
TI  - New ideas and advancing technologies in periodontology: surgical options with
      advancing technologies.
AB  - Extensive clinical studies over the last two decades have documented the
      effectiveness of both non-surgical and surgical periodontal therapy. When deemed
      necessary, surgery is usually performed as an elective phase of therapy, within a
      programme of ongoing maintenance care. Traditionally surgical therapy has been
      aimed at the treatment of the periodontal pocket by resective procedures.
      However, research has now focused on reconstructive surgery, with the objective
      of regenerating the structure of the lost periodontium (cementum, periodontal
      ligament and also alveolar bone). With advancing technology, materials and
      surgical modalities that have been advocated to facilitate periodontal
      reconstruction fall into the following main categories: 1. Chemical and
      biochemical conditioning agents, e.g. citric acid, fibronectin, tetracycline,
      growth and differentiation factors. 2. Transplants of autogenous or allogeneic
      (osteogenic or osteoinductive) materials, e.g. osseous coagulum, decalcified
      freeze-dried bone allograft. 3. Implants of alloplastic (osteoconductive)
      'filler' materials, e.g. hydroxyapatite, tricalcium phosphate. 4. Guided tissue
      regeneration (GTR) utilising membranes, e.g. Teflon (e-PTFE), collagen,
      polylactic acid. 5. Combined techniques, e.g. GTR and allograft/alloplast. The
      scientific evaluation and the role of these reconstructive surgical procedures in
      contemporary dental practice is discussed in this paper.

PMID- 8138317
TI  - Rules of infection control.
AB  - The subject of infection control in dentistry has aroused much controversy and
      debate during the past decade as a result of the global spread of the human
      immunodeficiency virus infection. Consequently a number of regulatory bodies have
      promulgated guidelines for infection control in dentistry and the current
      consensus is that the 'universal infection control' policy--which considers every
      patient as infectious--should be the norm in every dental practice. The reasons
      for this are the asymptomatic carriage of pathogens due to the sub-clinical
      nature, the prodromal period and the carrier state associated with a number of
      diseases. The universal infection control rules should encompass six elements:
      routine patient evaluation, personal protection with barrier techniques,
      instrument sterilisation including sterilisation control, surface and equipment
      disinfection, asepsis in the laboratory and appropriate disposal of contaminated
      waste including sharps. Finally, practitioners should attempt to keep abreast of
      the rules and regulations related to the subject of infection control in
      dentistry which are continuously evolving due to the steadily increasing data
      pool on infectious diseases and their modes of prevention.

PMID- 8138318
TI  - Dental survey: patient attitudes in Oman.
AB  - A questionnaire was designed to assess the attitude of Omani people to the state
      of their teeth, their personal oral hygiene and their acceptance of dental care.
      The questions were formulated to provide information without the need for dental
      examination. In Oman, as opposed to industrialised countries, the rate of dental
      decay is on the increase. In addition, there is a high prevalence of periodontal
      diseases as observed by this survey as well as some previous studies. The results
      of this nationwide survey, in connection with two previous field and clinical
      studies, indicate that more importance must be given to oral hygiene education
      together with increased facilities for treatment.

PMID- 8138319
TI  - Prosthodontic care of elderly edentulous patients.
AB  - Elderly people tend to gradually lose more of their ability to adjust. This
      pertains as much to changes within the oral cavity as to the general things in
      life. It is, therefore, advisable to make only small changes within the oral
      cavity at any one time. The goal of producing a complete denture should be
      attained in small steps with the aid of 'add on dentures'. Existing, successfully
      worn, complete dentures which have become inadequate, should not be replaced but
      should be rebuilt step by step. In addition, a 6 month recall system is strongly
      recommended.

PMID- 8138320
TI  - Development and harmonisation of the norms and parameters in biological testing
      protocols designed for root canal sealing materials within the European
      Community.
AB  - The EC has mounted the BIOMED 1 as a specific programme to facilitate cooperative
      research programmes in identified areas of interest throughout Europe. They have
      recently announced support under this programme for a joint initiative designed
      to evaluate in vitro and in vivo methods of biological testing of root canal
      sealing materials. This proposal was prepared by a group of research workers in
      the field. It provides a summary of the current suggested protocols for the
      biological testing of dental materials and then provides a detailed protocol of
      the studies to be carried out in the joint programme which commenced in January
      1993. The authors are publishing the proposal to invite comments from colleagues
      and interested parties.

PMID- 8138321
TI  - Measurement of confidence levels of new UK dental graduates: an approach to
      academic audit.

PMID- 8138322
TI  - The professional role of the dentist under the aspects of precancer and cancer
      diagnosis and management.

PMID- 8138323
TI  - The value of dentifrices and mouthrinses in caries prevention.
AB  - This paper reviews the current place of dentifrices, toothbrushes and rinses in
      the personal dental products market using data from the United States as an
      illustration. The clinical evolution of fluoride in dentifrices and rinses is
      briefly outlined, as is the changing view of the balance between the systemic and
      topical effects of the element on preventing dental caries. Issues involved in
      the current scientific arena are described as are issues related to caries trends
      and preventive technologies that deserve attention in the future.

PMID- 8138324
TI  - The science behind caries prevention.
AB  - Many agents have been shown to have an anticaries effect or to have the potential
      for such an effect. They can be categorised by their modes of action into three
      groups: those which affect plaque and plaque bacteria, those which affect tooth
      enamel chemistry and those which buffer oral pH. To be effective clinically,
      agents must not only possess intrinsic efficacy but also good oral retention
      characteristics. Currently, chlorhexidine is arguably the only antibacterial
      agent to have inhibited caries in humans, but is not employed in anticaries
      dentifrices and mouthrinses intended for long-term unsupervised daily use because
      of formulation difficulties and undesirable side effects such as tooth stain.
      Certain calcium salts and xylitol may also exert some clinical effect. The only
      extensively clinically-proven agent is fluoride. Well established reasons for the
      success of fluoride are its abilities to inhibit demineralisation of enamel and
      to enhance the remineralisation of incipient caries lesions. Recent research has
      highlighted the persistence of fluoride in saliva and plaque at potentially
      active concentrations between successive regular applications of dentifrices and
      mouthrinses as a further important mechanistic step. Oral fluoride retention
      studies can explain recent clinical observations of increased efficacy of sodium
      fluoride dentifrices compared with sodium monofluorophosphate dentifrices of
      equivalent fluoride content.

PMID- 8138325
TI  - Mouthrinses: recent clinical findings and implications for use.
AB  - Fluoride mouthrinses have been used extensively for the past 15 years to prevent
      dental caries in children. It has been demonstrated to reduce the incidence of
      dental caries in children by an average of 30 per cent. For individual patients,
      dentists should continue to recommend fluoride mouthrinsing at home, based upon
      the individual's caries activity or risk. This is true whether or not the patient
      is also receiving the benefits of community water fluoridation. School-based
      fluoride mouthrinsing programmes are recommended only in fluoride-deficient
      communities. Its effectiveness will be determined by the caries activity of the
      participants and the cost to reduce the disease level to an anticipated 30 per
      cent. Among all the topical fluoride agents, fluoride mouthrinses remain a safe
      and effective means of controlling dental decay in children and adolescents.

PMID- 8138326
TI  - Dentifrices: recent clinical findings and implications for use.
AB  - Since fluoride dentifrices first became available over 30 years ago many
      formulation changes regarding fluoride type, concentration and abrasive systems
      have occurred to improve stability, compatibility, and also bioavailability of
      active ingredients. As a result, it is now established that from 1000-2800 ppm F,
      there is a dose-response relationship. However, at fluoride levels below 1000
      ppm, efficacy has yet to be established fully. In the recent past, meta-analytic
      techniques employed on data concerning > 14,000 clinical trial subjects from 12
      studies, have established that the use of NaF in a correctly formulated silica
      base provides superior caries protection than does either an NaF + SMFP, or SMFP
      dentifrice. Furthermore, the incorporation of anti-calculus and anti-microbial
      agents into fluoride dentifrices has not been shown to have any effect--either
      beneficial or adverse--on caries levels. Investigations designed to optimise the
      benefit obtained from fluoride-containing toothpastes, have demonstrated that
      toothbrushing frequency and post-brushing oral rinsing habits can significantly
      affect caries levels, as assessed over a 3-year period. However, as dentifrice
      ingestion by young children is now an established fact, care must be exercised
      when advising parents regarding fluoridated dentifrice usage as part of a
      prevention regime for children under 6-7 years of age. Nonetheless, while there
      would appear to be a dentifrice-related fluorosis problem in North America, such
      evidence as currently exists within the UK, does not indicate that the level of
      symmetrical mottling currently observed (< 6 per cent in > 8,500 12-14-year-olds)
      constitutes any public health problem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138327
TI  - Serotonergic mechanisms in hypertension.
AB  - Serotonin and abnormal serotonergic activity (both central and peripheral) may
      play a role in pathogenesis of essential hypertension. Serotonin acts chiefly via
      three types of receptors namely S1, S2 and S3 serotonergic receptors. Besides
      being vasoactive, it has some inotropic and chronotropic properties and also
      affects blood rheology. It has stimulating effect on renin and aldosterone
      secretion. The action of other vasoactive substances like norepinephrine and
      angiotensin II are amplified. All these physiological effects of serotonin
      strongly support the hypothesis that it may be involved in hypertension. The
      advent of serotonin antagonists in lowering blood pressure has further
      substantiated this hypothesis.

PMID- 8138328
TI  - Assessment of regional myocardial performance with end-systolic pressure length
      and thickness relationships.
AB  - Although end-systolic pressure length and thickness relationships (ESPLR, ESPTR)
      are now widely used as substitutes for the end-systolic pressure volume
      relationships, there are some reservations about their use as an index of left
      ventricular (LV) performance. This study addressed three issues, namely: (1)
      which loading technique (decreasing preload by inferior vena cava (IVC) balloon
      occlusion or increasing systolic pressure by aortic constriction) is the most
      likely to yield usable data; (2) reproducibility of these relationships over a 30
      min period; and (3) whether by using end-ejection (zero aortic flow) as a
      definition of end-systole, ESPLR and ESPTR can be used to characterize myocardial
      performance independent of load. Thirteen anesthetized beagles, weighing 16-25
      kg, were used for this study, and were instrumented with sonomicrometers. We
      found that when ESPLR and ESPTR were constructed from data derived during aortic
      constriction, the slopes of these relationships were steeper and more curvilinear
      than when they were constructed from data recorded during IVC occlusion. In
      addition, the mean between ESPLR, ESPTR obtained 30 min apart was small, although
      there was a fair degree of variability between the first and second measurements.
      Using end-ejection to define end-systole, both ESPLR and ESPTR were relatively
      insensitive to loading conditions (LV end-diastolic pressure of 8-12 mmHg and 14
      18 mmHg, aortic systolic pressure of 7-10 mmHg and 20-25 mmHg above baseline (in
      terms of the slope and shift (leftward or rightward) in these relationships, but
      were sensitive to inotropic interventions (dobutamine 2.5 micrograms/kg per min
      and 5 micrograms/kg per min). We conclude that, ESPLR and ESPTR, defined from
      measurements at end-ejection, can be used as adequate descriptors of regional
      myocardial performance if they were constructed from data over a similar pressure
      range during IVC balloon occlusion.

PMID- 8138329
TI  - The progression of mild congenital aortic valve stenosis from childhood into
      adult life.
AB  - We studied 187 patients who presented with mild congenital aortic valve stenosis
      or a bicuspid aortic valve without stenosis at presentation; 63% were males.
      Information on all clinical events was obtained, and patients were traced to
      assess current clinical status. RESULTS: The median age at presentation was 2
      years (range, 0-15). Additional cardiac lesions occurred in 51 patients, more
      commonly in patients presenting under 1 year of age (P < 0.0001). The median
      duration of follow-up was 10 years (range, 1-28); seven patients were lost to
      follow-up. Thirty-two patients progressed to require intervention (28 surgical,
      five balloon valvuloplasty) at a median age of 10.5 years. No patient who
      presented with a bicuspid aortic valve required intervention. Two patients
      developed endocarditis. There were eight deaths; four after surgery for aortic
      stenosis and four due to other cardiac lesions. There were no sudden deaths.
      Actuarial and hazard analysis showed that progression beyond mild stenosis was
      closely related to duration of follow-up. CONCLUSIONS: Congenital aortic valve
      stenosis is most frequently mild at presentation. Progression is related to
      duration of follow-up. Fewer than 20% of patients are likely to still have mild
      stenosis after 30 years. Follow-up into adult life is essential.

PMID- 8138330
TI  - Effects of captopril on myocardial protection during cardioplegia.
AB  - The study aimed at checking effects exerted by captopril (C) on human myocardial
      ACE system as well as the role played by tissue ACE inhibition in reducing
      reperfusion damage. A human experimental model was used during cardioplegia due
      to aorto-coronary-by-pass (CABG). Fifty-four patients with coronary artery
      disease affecting 3 vessels having suffered from acute myocardial infarction
      anterior (AMI-ant), homogeneous as far as ejection fraction (35-55%), number of
      grafts (3), clamping time, age and sex, were randomised in a double blind
      experiment, and were given captopril or placebo (P). A total of 4 mg/l Captopril
      was mixed into the cardioplegic solution with blood according to the method of
      Buckberg (Buckberg GD. J Thorac Cardiovasc Surg 1987; 93: 127-139). Eight samples
      (blood/perfusate) were obtained from each patients and norepinephrine (NE),
      epinephrine (E) were assayed using an HPLC technique. Angiotensin I was assayed
      by RIA. CK was also assayed (units/ml). Blood/perfusate samples were taken during
      CABG: (1) pre-pump; (2) pump sample; (3) pump preclamping; (4) coronary sinus;
      (5) coronary sinus sample during reperfusion; (6) coronary sinus during warm
      reperfusion; (7) after clamping sample; (8) after decanulation; RESULTS:
      Captopril group (29 patients): angiotensin I: (1) 8.15; (2) 7.0; (3) 7.31; (4)
      8.45; (5) 8.93; (6) 8.73; (7) 9.07; (8) 9.40; versus placebo: (1) 7.09, (2) 7.43;
      (3) 7.80; (4) 9.31; (5) 9.01; (6) 8.35; (7) 8.85; (8) 8.07 ng/ml, probability,
      not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138331
TI  - Tumor necrosis factor-alpha as a myocardial depressant substance.
AB  - Most patient with sepsis and septic shock develop significant derangements of
      myocardial function. The presence of a circulating myocardial depressant
      substance (MDS) has been suggested to be the major cause of myocardial depression
      in sepsis and septic shock. MDS is still not fully characterized by chemical
      means, and there is no consensus regarding its identity. Nevertheless, high
      levels of MDS activity can be found in sera from patients with sepsis and septic
      shock. Furthermore, MDS has been shown to have a number of specific
      characteristics. These characteristics have also been described with tumor
      necrosis factor-alpha (TNF), a cytokine that is well recognized to be a primary
      mediator in the pathogenesis of infection, tissue injury, inflammation and shock.
      In this review it is suggested that TNF is an MDS, and that the cardiovascular
      injury and myocardial depression during sepsis and septic shock involve a final
      common pathway, where TNF may have an important role in this common pathway.

PMID- 8138332
TI  - Neutrophil adherence-augmenting and chemotactic plasma activities in acute
      myocardial infarction: effect of fibrinolytic treatment.
AB  - Polymorphonuclear neutrophils (PMNs) participate in the development of myocardial
      reperfusion injury during fibrynolytic treatment. In 40 patients with acute
      myocardial infarction, we evaluated the effect of streptokinase treatment on
      plasma activity augmenting PMN adherence and chemotactic plasma activity in
      peripheral venous blood with the use of neutrophils obtained from healthy donors.
      In all patients we observed the appearance of marked plasma chemotactic activity
      and plasma activity augmenting PMN adherence. Peak values of both plasma
      activities in the conventionally treated group were reached on the third day
      following the onset of symptoms. In streptokinase treated patients both plasma
      activities reached a peak on the second day after the onset of symptoms.
      Furthermore, streptokinase in vitro induced adherence of control PMNs in a dose
      dependent manner, as well as increasing both chemotaxis and random migration of
      control cells. Thus, both chemotactic plasma activity and neutrophil adherence
      augmenting plasma activity may be used for monitoring the inflammatory response
      to myocardial infarction. However, during fibrynolytic treatment the presence of
      chemotactic stimuli in peripheral blood may be affected by streptokinase per se.

PMID- 8138333
TI  - Prognosis of myocardial infarction and brain functional asymmetry.
AB  - Seventy-eight men (mean age, 47.0 +/- 1.1 years) who had suffered from myocardial
      infarction were examined. Blood cholesterol, lipoproteins, triglycerides, insulin
      and cortisol concentrations were compared in patients with left hemisphere or
      right hemisphere cerebral dominance. Patients with left hemisphere dominance had
      more serious disease and much higher levels of blood cholesterol and
      lipoproteins. Patients with right hemisphere dominance had the highest levels of
      blood cortisol and insulin. The brain's functional asymmetry may be one of the
      risk factors for coronary atherosclerosis in subjects under the age of 50 years.

PMID- 8138334
TI  - Cardiovascular symptoms, electrocardiographic abnormalities, and associated risk
      factors in an elderly Chinese population.
AB  - The aim of this study was to determine the prevalence of angina and possible
      infarct (WHO cardiovascular questionnaire) and electrocardiographic abnormalities
      (Minnesota Coding) in elderly Chinese subjects aged 70+ years living in Hong
      Kong, and the association with some cardiovascular risk factors. A subsample of
      197 subjects (96 men, 101 women) selected according to geographical area from a
      territory-wide health survey consisting of 2032 elderly subjects selected by an
      age and sex stratified random sampling method was studied. Overall, 7% of men and
      9% of women had symptoms suggestive of angina, while 6% of men and 4% of women
      had symptoms suggestive of possible infarct. There were fewer symptoms in the 80+
      age group. Forty-two percent of men and 35% of women had normal
      electrocardiograms. The prevalence of probable ischaemic heart disease (using the
      Whitehall Criteria) was 6% for men and 7% for women, while the figures for
      possible disease were 23% and 25%, respectively. The percentage with
      abnormalities increased with age. The prevalence of coronary heart disease
      defined by the presence of symptoms, a history of known disease plus use of
      medication, and electrocardiographic abnormalities suggestive of probable
      disease, was 26% for men and 27% for women. These findings were comparable with
      studies in elderly Caucasian populations. Only a higher socioeconomic grouping
      and lower HDL cholesterol were identified as associated risk factors. It is
      concluded that the prevalence of coronary heart disease in the elderly Chinese
      population in Hong Kong is at least as high in Caucasian populations, and few
      modifiable risk factors were identified in the elderly aged 70 years and over.

PMID- 8138335
TI  - Late symptom recurrence after successful coronary angioplasty: angiographic
      outcome.
AB  - OBJECTIVES: To determine the angiographic appearance of the dilated coronary
      artery and the cause of symptoms in patients who presented with a return of chest
      pain more than 1 year after successful percutaneous transluminal coronary
      angioplasty (PTCA). DESIGN: Retrospective analysis of coronary angiograms and
      review of case histories. PATIENTS AND METHODS: 112 patients who underwent repeat
      coronary arteriography for investigation of chest pain 13-105 (median, 30) months
      after successful coronary angioplasty were studied. All patients were free of
      symptoms for at least 12 months after the initial angioplasty. RESULTS: A return
      of chest pain was attributed to restenosis in 12 patients (11%), to a new lesion
      or worsening of pre-existing coronary lesion in 56 patients (50%), and to both
      restenosis and stenosis in non-dilated coronary segments in 10 patients (9%).
      There was no restenosis in 112 of the 134 dilated lesions (84%). In 34 patients
      (30%), there was no significant stenosis in either dilated or non-dilated
      coronary segments. CONCLUSIONS: In patients undergoing coronary angiography for
      the investigation of recurrent chest pain more than 1 year after successful
      coronary angioplasty, the majority of dilated coronary segments had a good
      angiographic appearance. Late onset angina following PTCA is usually due to new
      coronary lesions or worsening of pre-existing mild stenosis.

PMID- 8138336
TI  - The effect of successful coronary angioplasty on feelings of exhaustion.
AB  - Excess fatigue and exhaustion are among the most prevalent premonitory complaints
      of myocardial infarction and sudden cardiac death. These feelings may reflect
      subclinical heart disease, prolonged psychological tension, or both. The present
      study investigates to what extent coronary artery disease explains exhaustion.
      For this purpose, the relationship between the severity of coronary artery
      disease and exhaustion, and the relief of exhaustion after successful
      percutaneous transluminal coronary angioplasty (PTCA) is investigated. Patients
      who had a successful elective PTCA (N = 120) were evaluated on feelings of
      exhaustion on admission, 2 weeks after discharge and 6 months after discharge,
      making use of the Maastricht Questionnaire. Multiple regression analyses were
      used to investigate to what degree exhaustion on admission and after PTCA was
      determined by the extent of coronary artery disease and other patient
      characteristics. Severity of coronary artery disease before PTCA was positively
      associated with exhaustion and successful PTCA resulted in a significant decrease
      of exhaustion scores (P < 0.001). However, less than 5% of the variance of the
      exhaustion scores before PTCA could be explained by severity of coronary artery
      disease (R2 = 0.04, F = 5.1, P = 0.03). The majority of patients who were
      exhausted before PTCA remained exhausted after PTCA. Exhaustion was present in
      75% of the patients before PTCA and in 65% 2 weeks after PTCA, which indicates
      that restoration of coronary perfusion by successful PTCA does not substantially
      reduce the number of exhausted patients. At 6 months, exhaustion was present in
      60% of the patients, and there was no difference between patients with and
      without typical anginal complaints at that time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138337
TI  - Cardioinhibitory response to carotid sinus massage in patients with coronary
      artery disease.
AB  - The relationship between cardioinhibitory response to the carotid sinus massage
      and the severity of coronary artery lesions and left ventricular impairment was
      investigated in 86 patients who underwent coronary angiography. The study group
      (Group 1) comprised 63 patients who had coronary lesions and the control group
      (Group 2) comprised 23 patients who had normal coronary arteries. There was no
      significant relationship between the severity of coronary artery lesions and the
      cardioinhibitory response to the carotid sinus massage in the study group.
      However, there was a positive correlation (r = 0.478, P < 0.01) between total
      left ventricular segment scores and the maximal change in RR interval (%) during
      the right carotid sinus massage in the study group. During the right carotid
      sinus massage, maximal change of RR interval (%) was significantly higher in
      patients who had segmental wall motion abnormalities than in patients who did not
      (83.0 +/- 72.4% vs. 32.9 +/- 42.5%, P < 0.01, respectively). In the patients who
      could have echocardiographic measurements there was negative correlation between
      fractional shortening value and maximal change of RR interval (%) (right massage;
      r = -0.482, P < 0.01, left massage; r = -0.334, P < 0.05). In conclusion, we
      found a significant relationship between the cardioinhibitory response to carotid
      sinus massage and the presence and severity of the segmental wall motion
      abnormalities and left ventricular impairment in patients with coronary artery
      disease.

PMID- 8138338
TI  - Myocardial ischemia after 5-fluorouracil chemotherapy.
AB  - A 40-year-old male patient with carcinoma of the tonsil was put on a 5
      fluorouracil and cisplatinum regimen. On day 2 during 5-fluorouracil infusion, he
      had features of myocardial ischemia manifesting as angina and ST-elevation in
      ECG. These vasospastic ischemic changes subsided after nitroglycerine plus
      nifedipine therapy. Such vasospastic toxicity of 5-fluorouracil is rare and few
      such cases have been reported.

PMID- 8138339
TI  - Radiofrequency catheter ablation of idiopathic left ventricular tachycardia in
      young adults.
AB  - We performed radiofrequency catheter ablation of idiopathic ventricular
      tachycardia arising from the left ventricle, in two 15-year-old patients.
      Activation mapping during induced tachycardia revealed an origin from the mid
      septal region of the left ventricle in both patients. Local activation times and
      pacemapping were used to select the target site for successful ablation. At
      follow-up, both patients are without symptoms.

PMID- 8138340
TI  - Superiority of transoesophageal echocardiography in detection of multichambered
      multiple myxoma.
AB  - We describe a rare case of a sporadiac form of multiple myxoma and highlight the
      unusual combination of left atrial and right ventricular tumors. Transoesophageal
      echocardiography proved superior to precordial imaging in detecting all four
      masses (two in left atrium and two in right ventricle).

PMID- 8138341
TI  - Case of Williams elfin facies syndrome with pulmonary artery sling.
AB  - We report the presence of pulmonary artery sling in a 4-year-old girl with the
      Williams elfin facies syndrome. A history of heavy and persistent wheezing during
      the first few months of life, associated with the current presentation of heart
      murmur and pulmonary stenosis, led us to investigate the presence of pulmonary
      artery sling. Both pulmonary artery sling and cardiovascular anomalies in
      Williams elfin facies syndrome have previously been linked to developmental
      anomalies of the 6th aortic arch. This appears to be the second reported case of
      this rare combination of anomalies.

PMID- 8138342
TI  - Withdrawal phenomenon after abrupt cessation of nifedipine in stable angina
      pectoris.
AB  - We investigated the effect of abrupt cessation of nifedipine after regular
      administration (20 mg, four times daily) for 5 weeks in seven patients with
      stable angina pectoris. A rebound decrease in exercise tolerance and increase of
      exercise-induced myocardial ischaemia were registered on the first day of
      nifedipine withdrawal.

PMID- 8138343
TI  - Temporary balloon closure of a postinfarction interventricular septal rupture.
AB  - The technical aspects of temporary closure of a postinfarction interventricular
      septal rupture in a 76-year-old woman in critical circulatory status ruling out
      conservative therapy and making surgical management unfeasible, are described.
      The patient was in cardiogenic shock with hepatorenal failure in acute myocardial
      infarction of both the anterior and posterior walls. A balloon catheter developed
      in our unit was employed to close the rupture.

PMID- 8138344
TI  - Incomplete Fmoc deprotection in solid-phase synthesis of peptides.
AB  - During solid-phase peptide synthesis of homo-oligopeptides containing leucine or
      alanine using the Fmoc strategy, we have observed ineffective N-alpha
      deprotection with piperidine in a sequence-dependent manner. Incomplete
      deprotection was found to be associated with subsequent slow or incomplete amino
      acid coupling. Optimization of the deprotection step was carried out by varying
      the experimental conditions e.g. deprotection time, temperature, solvents and
      addition of chaotropes. Coupling and deprotection steps have been investigated
      using color monitoring, as well as FAB MS and HPLC for product analysis. The
      phenomena of difficult coupling and deprotection steps in the investigated
      systems have been demonstrated to have the same physical chemical origins, beta
      sheet formation.

PMID- 8138345
TI  - Theoretical conformational analysis and synthesis of analogues of the
      heptapeptide antibiotic K-582 A.
AB  - A detailed theoretical conformational analysis of the linear heptapeptide
      antibiotic [Arg2]K-582 A (Arg-Arg-D-Orn-Thr-D-Orn-Lys-D-Tyr) was carried out. The
      results of the computer simulation suggest that the linear peptide has a high
      propensity to fold in solution into a quasi-cyclic conformation in equilibrium
      with pi(L-D) helices. The synthesis of two inactive analogues with an L-Lys in
      place of D-Orn3 or D-Orn5 confirms the importance of the proposed folding pattern
      for the occurrence of the antimicrobial activity of K-582 A.

PMID- 8138346
TI  - Interaction of calmodulin with synthetic deletion peptides of melittin.
AB  - The 26-residue peptide melittin present in bee venom has been shown to bind
      calmodulin tightly. In this study we synthesized the following series of deletion
      peptides of melittin by the solid-phase method: Mel12, Mel13, Mel14, Mel15,
      Mel15F. The results of this study show that the deletion peptides Mel14 and Mel15
      have almost the same binding activity as the intact native peptide. Each deletion
      peptide forms a 1:1 complex with calmodulin according to electrophoresis
      analysis. When the tryptophanyl residue of Mel15 was replaced by the
      phenylalaninyl residue, the dissociation constant of the peptide-calmodulin
      complex increased. This shows the importance of the tryptophanyl residue for
      binding to calmodulin.

PMID- 8138347
TI  - Peptide-lanthanide interactions. Crystal structure of a europium(III)-triglycine
      complex.
AB  - Crystals of Eu-(Gly-Gly-Gly).(H2O)5.(ClO4)3 are triclinic, spacegroup P1 with a =
      9.123 (2), b = 11.185 (5), c = 11.426 (2) A; alpha = 90.79 (2), beta = 98.08 (1),
      gamma = 98.57 (2) degrees; Z = 2. The europium cation is surrounded by four
      oxygens from three different peptide units and four oxygens from water molecules.
      The geometry around the metal is a distorted bi-capped trigonal prism. The
      peptide backbone conformation in this complex is compared with those in the free
      peptide and in various metal complexes. Considerable differences are observed
      between Eu(III) and Ca(II) complexes of triglycine.

PMID- 8138348
TI  - Interaction with model membrane systems induces secondary structure in amino
      terminal fragments of parathyroid hormone related protein.
AB  - The secondary structure of amino terminal fragments of human parathyroid hormone
      related protein (PTHrP) in aqueous solution, in trifluoroethanol solution and in
      the presence of model membrane systems has been studied by circular dichroism
      (CD) spectroscopy. Far-UV CD spectra of PTHrP 1-40, 1-34 amide, 7-34 amide and 1
      16 are consistent with a predominantly unordered structure. Addition of
      trifluoroethanol stabilized alpha-helical structure in the 1-34 amide and 7-34
      amide peptides. The effect reached a plateau at a trifluoroethanol concentration
      of approximately 40%, and a helix content of some 23 residues was determined.
      PTHrP 1-34 amide interacted with palmitoyloleoylphosphatidyl serine vesicles and
      exhibited an increased alpha-helix content of approximately 12 helical residues.
      Similar results were observed for monomyristoyllecithin micelles and sodium
      dodecyl sulfate micelles. No interaction with dimyristoylphosphatidylcholine
      vesicles was detected by CD. The ability to bind to palmitoyloleoylphosphotidyl
      serine vesicles was also a feature of the 1-40 and 7-34 fragments, while the 1-16
      fragment was apparently unaffected by interaction with this model membrane
      system. These results indicate that the conformational properties of the
      functionally significant amino terminal 1-34 region of PTHrP parallel those
      reported for the corresponding, but largely nonhomologous, region of parathyroid
      hormone. Conformational similarities may account for the ability of PTHrP to
      mimic the functional properties of parathyroid hormone.

PMID- 8138349
TI  - A new synthesis of Rink's polymer, 4-(2',4'
      dimethoxyphenylhydroxymethyl)phenoxymethylpolystyrene .
AB  - For solid-phase peptide synthesis, 2,4-dimethoxy-4'-hydroxbenzhydrol linker was
      prepared via lithium borohydride reduction of 2,4-dimethoxy-4'
      hydroxybenozophenone. The potassium salt of the linker was coupled to
      chloromethylpolystyrene. This method proved to be better than use of the cesium
      salt. This new synthesis gave a polymer with appropriate structure and a good
      degree of substitution.

PMID- 8138350
TI  - Sequence-dependent modification of Trp by the Pmc protecting group of Arg during
      TFA deprotection.
AB  - The extent of transfer of the Pmc protecting group from the guanidino group of
      arginine to the side chain of tryptophan depends on the spacial distance of these
      side chains. When these two amino acids are separated by one amino acid, the
      transfer of the Pmc protecting group is the most pronounced, and it cannot be
      completely prevented by the use of currently utilized scavenger mixtures. The
      extent of this side reaction also depends on the amino acid separating the
      arginine and tryptophan residues and position of tryptophan within the peptide
      chain as well as on the type of the solid-phase carrier.

PMID- 8138351
TI  - The pseudo-beta I-turn. A new structural motif with a cis peptide bond in cyclic
      hexapeptides.
AB  - Synthesis and conformational analysis of three cyclic hexapeptides cyclo(-Gly1
      Pro2-Phe3-Val4-Xaa5-Phe6), Xaa = Phe (I), D-Phe (II) and D-Pro (III), were
      carried out to examine the influence of proline on the formation of reverse turns
      and the dynamics of hydrophobic peptide regions. Assignment of all 1H and 13C
      resonances was achieved by homo- and heteronuclear 2D-NMR techniques (TOCSY,
      ROESY, HMQC, HMQC-TOCSY and HMBCS-270). The conformational analysis is based on
      interproton distances derived from ROESY spectra and homo- and heteronuclear
      coupling constants (E.COSY, HETLOC and HMBCS-270). For structural refinements
      restrained molecular dynamics (MD) simulations in vacuo and in DMSO were
      performed. Each peptide exhibits two conformations in DMSO solution due to cis
      trans isomerism about the Gly-Pro peptide bond. Surprisingly the cis-Gly-Pro
      segment in the minor isomers is not involved in a beta VI-turn, but forms a turn
      structure with cis-Gly-Pro in the i and i + 1 positions. Although no stabilizing
      hydrogen bond is found in this turn, the phi- and psi-angles closely correspond
      to a beta I-turn [Pro2: phi(i + 1) -60 degrees, psi(i + 1) -30 degrees; Phe3:
      phi(i + 2) -100 degrees, psi(i + 2) -50 degrees]. Hence we call this structural
      element a pseudo-beta I-turn. As expected, in the dominating all-trans isomers
      proline occupies the i + 1 position of a standard beta I-turn. Therefore, cis
      trans isomerization of the Gly1-Pro2 amide bond only induces a local
      conformational rearrangement, with minor structural changes in other parts of the
      molecule. However, the geometry of the other regions is affected by the chirality
      of the i + 1 amino acid for both isomers (beta I for Phe5, beta II' for D-Phe5 or
      D-Pro5).

PMID- 8138352
TI  - Synthesis of methylated phenylalanines via hydrogenolysis of corresponding
      1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids. Synthesis and biological
      activity of oxytocin analogs with methylated phenylalanines in position 2.
AB  - A new method of synthesizing ortho-methylated phenylalanines has been developed.
      Phenylalanines with at least one free ortho-position undergo a Pictet-Spengler
      cyclization with formaldehyde followed by hydrogenolytic splitting of the
      endocyclic benzylic C--N bond of 1,2,3,4-tetrahydroisoquinolines and afford
      corresponding ortho-methyl derivatives. Repeating this reaction sequence on the
      ortho-substituted phenylalanines yielded ortho,ortho-disubstituted derivatives,
      and para-substituted phenylalanines yielded ortho,para-disubstituted analogs. Our
      modified method of cyclization preserved the configuration at the chiral center:
      hydrogenolysis, on the other hand, led to racemization. Incorporation of the
      methylated phenylalanines into position 2 of oxytocin led to, in the case of the
      D-isomers, potent uterotonic inhibitors.

PMID- 8138353
TI  - Purification and characterization of gonadotropin I and II from pituitary glands
      of tuna (Thunnus obesus)
AB  - The duality of teleost pituitary gonadotropins was established in an advanced
      marine fish, the tuna (Thunnus obesus). Two different molecular forms of
      gonadotropins, designated tGTH I and tGTH II, were isolated from an alcoholic
      extract of pituitary glands following ion-exchange chromatography and reversed
      phase HPLC. Both tGTH I and tGTH II stimulated estradiol-17 beta and testosterone
      production in tuna ovarian follicles in vitro, although responses to tGTH II were
      significantly greater than those to tGTH I. Each gonadotropin consisted of alpha-
      and beta-subunits. tGTH I was stable in acidic conditions, whereas tGTH II
      dissociated into two subunits after acid treatment. Alpha subunits of tGTH I and
      tGTH II had identical amino acid sequences of 94 amino acid residues. The tGTH I
      beta and tGTH II beta consisted of 102 and 115 amino acid residues, respectively,
      and showed 35% sequence identity. tGTH I beta is structurally more similar to
      salmon GTH I beta than to salmon GTH II beta, whereas tGTH II beta is more
      similar to salmon GTH II beta. Thus it is evident that the tuna pituitary gland
      produces two chemically distinct gonadotropins.

PMID- 8138354
TI  - Direct assignment of disulfide bonds by Edman degradation of selected peptide
      fragments.
AB  - Disulfide linkages in peptides or proteins were analyzed by automated gas-phase
      Edman sequencing performed in minimized reducing agents. If cystine linkage was
      regulated at the same position in two peptides during peptide preparation, the
      diphenylthiohydantoin derivative of cystine was significantly recovered by Edman
      reaction. In contrast, when the crosslinked half cystines were present at
      different positions in the peptides, the derivative could be poorly detected.
      Upon direct sequence analysis of intact bovine insulin, the PTH derivatives of
      cystine from both Cys-A7 and Cys-B7 were significantly released after Edman cycle
      7 and gave approximately 20% recovery of common PTH amino acids. However, Cys-A11
      linked to Cys-A6 was poorly detectable after Edman cycle 11. For general use of
      this method, proteins need to be subjected to several sets of proteolytic or
      chemical cleavages in the hope that at least one of the fragments will have
      cystine linkage at the same position. This method was applied to several
      fragments of platelet-derived growth factor B chain and brain-derived
      neurotrophic factor.

PMID- 8138355
TI  - Peptidic p-nitroanilide substrates of interleukin-1 beta-converting enzyme.
AB  - Peptidic p-nitroanilides are useful colorimetric substrates for enzymes. With the
      aim of developing a convenient, quantitative assay for inhibitors of interleukin
      1 beta-converting enzyme (ICE), we have explored three approaches to the
      synthesis of peptidic p-nitroanilides relevant to this enzyme. The first approach
      involved a late stage oxidation of a p-aminoanilide such as CbzValAlaAsp(beta-
      tert-butyl)-p-(t-Boc-amino)anilide. The second and third approaches used the
      preformed amino acid p-nitroanilides HAsp-p-nitroanilide hydrochloride and
      HAsp(beta-tert-butyl)-p-nitroanilide which were coupled iteratively with
      preactivated amino acid derivatives or with an appropriate peptide, respectively.
      While each approach had it merits and limitations, all three produced p
      nitroanilides that were substrates for ICE.

PMID- 8138356
TI  - On communication from patient to analyst: not everything is projective
      identification.

PMID- 8138357
TI  - Psychoanalysis today and tomorrow.

PMID- 8138358
TI  - What a psychoanalyst learned from the Holocaust and genocide.
AB  - This paper is concerned with certain aspects of the Holocaust as it concerns
      children of survivors and child survivors. It describes transposition and
      somatisation and a split in the superego in children of survivors, bringing as an
      example the case of Rachel. It goes on to describe the psyche of child survivors,
      the split in their ego, their somatisation and the effect it had on the id, the
      ego and the superego of child survivors. Time did not permit examination of
      another interest of mine, the psyche of the German persecutor who inflicted the
      atrocities on communists, socialists and gypsies as well as Jews and homosexuals
      as if they were vermin.

PMID- 8138359
TI  - Two discussions of 'The inner experiences of the analyst' and a response from
      Theodore Jacobs.

PMID- 8138360
TI  - Two discussions of 'The mind of the analyst' and a response from Madeleine
      Baranger.

PMID- 8138361
TI  - Two discussions of 'Theory in vivo' by Dennis Duncan.

PMID- 8138363
TI  - Some comments on Baranger's paper using Jacobs's clinical example.

PMID- 8138362
TI  - Some thoughts on the presentation and discussion of the clinical material of
      psychoanalysis.
AB  - This paper is intended to stimulate consideration of the problems we face as
      psychoanalysts in attempting to discuss our basic data: the material from the
      clinical setting. Some brief comments are made about the importance of this issue
      for progress in our field, in the context of several attempts by the author to
      present and discuss process material from psychoanalytical treatment, and also in
      the light of discussion at psychoanalytical conferences and congresses, such as
      the Amsterdam sessions devoted to the clinical papers by Jacobs and Duncan. The
      question of what is going when psychoanalysts present clinical material to each
      other and discuss it is approached: firstly, by drawing attention to some
      features of the context in which discussion of that report takes place; secondly,
      by considering what it is we are doing when we select what we report of a
      psychoanalytic session; and, thirdly, by exploring certain inherent features of
      the psychoanalytic situation itself and their impact on the construction of a
      report and the response to it of an audience. Taken together, it is argued, these
      three elements have quite far-reaching implications for how presenter and
      audience might usefully play their parts in clinical discussion, and on the
      nature of the culture of enquiry we need to develop if we are to have hopes of
      building psychoanalytic theory and technique grounded in observations of
      practice.

PMID- 8138364
TI  - Varieties of envious experience.
AB  - This paper discusses Melanie Klein's use of the concept of envy and some of the
      criticisms of it. Two ways of experiencing envy, ego-dystonic and impenitent, are
      described and illustrated in clinical detail. The paper concludes with a
      description of a model of the relation of giving and receiving, especially of the
      conscious and unconscious feelings involved in giving and receiving, for I
      believe that it is in this relation and its internalisation that envy is
      particularly likely to be aroused, diminished, exacerbated, or perpetuated.

PMID- 8138365
TI  - Envy and admiration.
AB  - Envy and admiration are analysed as alternative ways, in essential respects
      contrary to each other, to cope with situations of relative deprivation, when one
      becomes aware of having less of some good than some other has. In terms of
      phantasies and with respect to the organisation of the objects, envy is a
      paranoid-schizoid phenomenon, with hopelessness, persecutory phantasies, and
      object-splitting, whereas admiration is in the depressive position, with hope,
      sympathy, and compartmentalisation of the admired trait out of its whole-object
      context. The close relations between envy and admiration and narcissism are
      pointed out, as are the differences between admiration and idealisation.

PMID- 8138366
TI  - The patient's discovery of the psychoanalyst as a new object.
AB  - Two groups of contributions are reviewed and integrated: those pertaining to non
      interpretive elements that support the psychoanalytic process and some seminal
      papers on the therapeutic action of psychoanalysis. The notions of the
      psychoanalyst as a transference object and new object are conceptualised and
      differentiated. It is shown that the corrective analytic experience is related to
      the objective interpretation of transference distortions, this being the
      essential step in the process whereby the analyst emerges as a new object. This
      is contrasted with the discredited corrective emotional experience. Finally, it
      is suggested that in cases of structural deficit or developmental arrest,
      unverbalised features, such as the analyst's survival, the atmosphere of safety
      and tolerance, etc. are themselves implicit transference interpretations and that
      they are mutative.

PMID- 8138367
TI  - Playing and therapeutic action in child analysis.
AB  - From its inception, child psychoanalysis has used fantasy play as a window to
      both the content and process of children's inner worlds. Because of the link to
      action and primary process, young children's imaginary play is rich in symbolic
      expressions that facilitate analytic interpretive interventions addressing the
      conflicts impeding development. There are inevitable tensions between allowing
      play to emerge as a therapeutic process in its own right and the usual
      psychoanalytic emphasis on clarification, verbalisation and, above all,
      interpretation within and about the transference. For many children, the very act
      of playing carries much of the therapeutic work aimed toward facilitating their
      return to developmentally appropriate and adaptive psychic functioning. The
      mobilisation of capacities for play in the analysis allows children to do what is
      needed for their development to continue and makes use of the developmentally
      restorative functions of play in the service of therapeutic action.

PMID- 8138368
TI  - The dictator and his cure.
AB  - The role of notetaking in the case of Little Hans has been almost completely
      overlooked in the pertinent psychoanalytic literature. A focus on notetaking
      shows, among other things, how Freud's cherished little patient became a dictator
      and thereby took a decisive step in his analysis.

PMID- 8138369
TI  - The dynamic functions of the act of reading.
AB  - This study of 68 avid fiction readers demonstrated that for those who love
      fiction, deeply personal meanings pervade the act of becoming absorbed in a work
      and shape the ways that they can use fiction in their lives as a whole. Each
      respondent had a unique, largely unconscious relationship to the act of reading,
      a relationship that expressed themes and addressed functions related to self
      organisation, real and fantasized relatedness, affect regulation, and the
      repetition or working through of conflict. To the extent that these inner
      determinants of the reading experience became rigid and unyielding, readers
      derived less newness, richness, and depth, though not necessarily less benefit,
      from engagement in fiction. Greater flexibility allowed reading to take place in
      what Winnicott called potential space. It enabled readers to involve themselves
      in fiction without sacrificing either the work's uniqueness or their own inner
      life, so permitting them to create new experience.

PMID- 8138370
TI  - Demyelination as an epiphenomenon in multiple sclerosis.

PMID- 8138371
TI  - Grasp reflex strength from right and left hands is associated with pH stressor
      from the umbilical arterial blood in human newborns: handedness and sex-related
      differences.
AB  - Grasp reflex and its asymmetry was studied in relation to pH of the umbilical
      blood in human newborns, to examine whether the degree of acidity in fetal blood
      (birth stress) is associated with cerebral laterality. Low pH values were
      considered as an index for birth stress. Grasp-reflex strength was found to be
      directly related to pH in total sample. There were sex-related differences.
      Namely, this correlation was true only for female newborns, not for males. Right
      minus left grasp-reflex strength linearly increased with pH, i.e., low pH values
      were associated with left-hand dominance, but only in males. The grasp-reflex
      asymmetry was not related to pH in females. It was concluded that blood pH may be
      associated with motor asymmetry and motor development in human newborns, but show
      sex-related differences; female brain seemed to be more sensitive to pH changes
      than male brain. The results partly supported the Bakan's hypothesis that birth
      stress may be associated with left-handedness.

PMID- 8138372
TI  - Influence of premorbid personality and location of lesion on emotional
      expression.
AB  - Both premorbid personality characteristics and location of brain lesion have been
      proposed to account for emotional changes after cerebral damage. To explore the
      relative merits of each hypothesis, we compared the MMPI profiles of 30 epileptic
      patients, who showed either a euphoric or depressive reaction after injection of
      amobarbital into the right or left hemisphere, with the MMPI profiles of 30
      matched controls. There were no significant T-score differences between euphoric,
      depressed, or control patients on any of the MMPI scales. However, more patients
      with euphoric (42%) than depressed (0%) reactions had hypomania (scale 9) scores
      greater than 70 T. With regard to location of lesion, there was a statistically
      significant association between emotional reaction and side of amobarbital brain
      inactivation. Euphoria was more frequent following right, and depression was more
      common after left, hemisphere inactivation. Although support was found for both
      premorbid personality and lesion location in the genesis of emotional reactions
      after brain damage, results were more robust for location of lesion.

PMID- 8138373
TI  - Foot laterality during childhood: a review.
AB  - Recent reports suggest that footedness warrants consideration as a potentially
      useful measure of specific aspects of neuropsychological functioning. However,
      very few data are available concerning its developmental characteristics. This
      paper presents a review of studies describing the trichotomous distribution of
      foot laterality spanning the childhood years (ages 3- to 11). When compared to
      handedness characteristics in the same population, it was noted that right-side
      dominance (foot preference) was not as pronounced, and about twice as many
      exhibit no dominant limb (i.e., mixed). The predictable pattern of increasing
      right-sidedness with advancing age found in handedness was not obvious for foot
      laterality over this period of time. The mixed-footed phenomenon is addressed
      using the basic tenets of Annett's Right-Shift hypothesis and the unique cultural
      factors associated with foot behavior. Applied implications of these observations
      for neuropsychological assessment and motor skill instruction are discussed.

PMID- 8138374
TI  - Induction of c-fos expression in the rostral medulla of rats following
      electroacupuncture stimulation.
AB  - The present study was designed to examine the induction of c-fos mRNA and Fos
      like protein in the rostral medulla of awake rats following electroacupuncture
      (EA) stimulation, using in situ hybridization and immunohistochemical method.
      Rats were subjected to EA stimulation (100 Hz, 1-2-3 mA) for 30 min by inserting
      two needles into acupoints Zusanli (S36) and Sanyingjiao (Sp6) of each hind leg.
      Animals were sacrificed 1h and 2h after EA for in situ hybridization and
      immunohistochemical study, respectively. c-fos mRNA or Fos-like-immunoreactivity
      (FLI) neurons were densely distributed in the rostral ventromedial medulla (RVM),
      including raphe magnus nucleus, gigantocellular reticular nucleus,
      gigantocellular reticular nucleus alpha, as well as intermediate reticular
      nucleus. Neurons in the solitary tract nucleus also showed c-fos expression. The
      results suggest that the RVM may be an important region for mediating EA effect.

PMID- 8138375
TI  - A test of Kinsbourne's selective activation model.
AB  - Kinsbourne's selective activation model (1985) was investigated in a sample of 28
      strongly right-dominant males. Priming manipulations were hypothesized
      preferentially to activate a hemisphere and to decrease reaction time on an
      affect recognition task in the contralateral visual field. The left hemisphere
      manipulation consisted of subvocal verbal rehearsal, while imagery served as the
      right hemisphere task. Baseline performance was evaluated via a control
      condition. No priming was found, but the experimental tasks had significant
      interference effects. Interference was noted across visual fields for both
      experimental manipulations relative to the control condition, suggesting the
      hemispheres were not preferentially recruited. Furthermore, the processing of
      happy faces was more susceptible to interference than was that of angry faces.
      Conceptual and methodological issues are presented to account for the former
      finding and data relevant to the laterality of affect perception may explain the
      latter.

PMID- 8138376
TI  - Methodological and theoretical issues in neural network models of frontal
      cognitive functions.
AB  - Neural network models have made significant strides in recent years toward
      modeling of neuropsychological data. In particular, three different research
      groups, including that of the present authors, have simulated in model networks
      some of the behavioral effects of frontal lobe damage. In this article we review
      these models and discuss their significance in terms of hierarchical organization
      in the nervous system. These models, to varying degrees, incorporate several
      widely used neural network principles that have also been used to model a wide
      range of data in other areas such as categorization, conditioning, and motor
      control. These principles include associative learning, competition, opponent
      processing, neuromodulation, and interlevel resonant feedback. Specifically, we
      show how combinations of these principles serve to model the attentional
      requirements of cognitive tasks and motor plans.

PMID- 8138377
TI  - Speed and accuracy of aimed hand movements in left-handed human subjects: sex
      related differences in motor control.
AB  - Speed and accuracy in hand speed in relation to sex-related differences were
      studied in left-handed normal subjects. Hand skill was assessed by a peg moving
      task. Hand speed increased linearly with successive trials (motor learning). Left
      hand speed exhibited a higher learning capacity than right-hand speed. Right-hand
      speed and right-hand learning were equivalent in males and females. Left-hand
      speed was higher in females than males; left-hand learning was equivalent in
      males and females. Left minus right (L-R) hand speed decreased linearly with
      right-hand speed; left-hand speed did not influence L-R hand speed. Learning
      curves were constructed for each subject. Standard error of a learning curve was
      considered as accuracy of hand skill. In females, accuracy of hand movement
      decreased as hand speed increased. In males, only accuracy of right-hand speed
      decreased as right-hand speed increased; left-hand accuracy did not depend on
      left-hand speed. It was concluded that right brain controlling left hand in left
      handers has a higher capacity than left brain for motor learning; L-R hand speed
      was largely determined by left brain; accuracy in hand skill depends on both
      brains in females, and on only left brain in males; the female brain is more
      bilaterally organized than male brain in fine motor control.

PMID- 8138378
TI  - A longitudinal CNV study of the evolution and treatment of bipolar illness.
AB  - In a longitudinal CNV study of bipolar illness we followed the evolution of this
      illness in six bipolar patients by recording their CNV and mood changes as well
      as their psychopharmacological treatment for a period of 8 months. The
      longitudinal CNV recordings of these patients did not show changes corresponding
      to their mood variations. The most salient result emerging from this study was
      the consistency in the patterns of the records in different patients in spite of
      variations in their clinical state and medications. We believe that these
      electrophysiological parameters cannot be used as markers of the mental state in
      bipolar patients nor do they reflect specific drug effect. These findings are
      congruent with available data which do not support a linear relationship between
      a complex psychological process such as manic depressive illness and a single
      physical dimension of brain activity. Further studies are warranted for a deeper
      understanding of this phenomenon.

PMID- 8138379
TI  - Neuropsychological and emotional sequelae of eosinophilia-myalgia syndrome.
AB  - In recent years there has been an increasing number of cases presenting with a
      newly recognized multiple systemic disorder, Eosinophilia-Myalgia Syndrome (EMS),
      in the United States. This report documents demographic data and scores from
      intelligence, memory, neuropsychological, and achievement testing from eight
      patients, and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profiles
      obtained by nine patients, all of whom were referred to a doctoral level
      neuropsychologist in private practice. Intelligence scores revealed a Full Scale
      Mean IQ of 90.6, with a Verbal IQ Mean of 92.3, and a Performance IQ Mean of 90.9
      for the Wechsler Adult Intelligence Scale--Revised. For the Wechsler Memory
      Scale, the patients earned a mean Memory Quotient of 80.5. On the Halstead-Reitan
      Neuropsychological Test Battery, the patients earned a mean Impairment Index of
      .82, and Achievement Test scores on the Wide Range Achievement Test--Revised
      ranged from a grade level of 4th grade to a grade level of above 12th grade for
      reading, and from a grade level of 5th grade to a grade level of above 12th grade
      for arithmetic. Both the modal and mean MMPI-2 profiles had 2-3/3-2 two point
      codes suggesting feelings of depression, tension, nervousness, fatigue,
      helplessness, somatic complaints and overcontrol. In all, the neuropsychological,
      intellectual, memory and achievement test scores suggested a pattern of moderate
      to severe impairment and the MMPI-2 test scores suggested a pattern of moderate
      emotional disturbance.

PMID- 8138381
TI  - Factor analysis and computerized EEG: preliminary data on schizophrenic patients.
AB  - Factor Analysis can extract salient features from EEG data and reduce redundancy
      of multi-channel computerized EEG data. A 16-channel computerized frequency
      analysis of background brain electrical activity during 3 functional conditions
      (eyes closed, eyes open and hyperventilation) was carried out in two groups,
      fifty healthy subjects and twenty-three schizophrenics. The power log-transformed
      relative values of normal subjects and schizophrenic patients were submitted to
      Factor Analysis and the resulting factor scores were compared. Schizophrenics
      showed EEG abnormalities in delta 2, theta 1 and alpha 2 bands for the first
      factor, accounting for the eyes closed condition, and in theta 2 and beta 2 bands
      for the second factor, accounting for the eyes open condition. This preliminary
      study demonstrates the utility of Factor Analysis in managing and comparing
      computerized EEG data.

PMID- 8138380
TI  - Gender differences in the EEG during cognitive activity.
AB  - EEG activity of 16 adult volunteers. 8 male and 8 females was monopolarly
      recorded at P3 and P4 at rest and during solution of three series of tasks: one
      analytic, one spatial and one mixed demanding both kinds of processing. The
      following main effects were observed: Men showed significantly higher beta
      relative power than women, while women showed significantly higher alpha relative
      power than men during all conditions. Alpha relative power decreased, while theta
      relative power increased during tasks solution in both sexes. Beta relative power
      was significantly higher at the left parietal only in men. Interparietal
      correlation was significantly higher in women than in men during all conditions
      and bands. For the theta band it increased from baseline values during tasks
      solution in men, while in women it decreased during the analytic task.

PMID- 8138382
TI  - The N15 component of the brainstem auditory evoked potential: a measure of
      hippocampal activity in schizophrenics?
AB  - The negative wave component of the brainstem auditory evoked potential at
      approximately 15 ms has been found to be related to activity in the hippocampus.
      Since hippocampal abnormalities have been reported among schizophrenic patients,
      it is obvious that a reliable electrophysiological measure of hippocampal
      activity might be useful in the study of schizophrenia. For instance, it may be
      hypothesized that the N15 wave of the BAEP would be abnormally reduced in
      amplitude for schizophrenics compared to controls, based on the previously
      reported misalignment of neurons in the hippocampus for schizophrenics. The
      measurement of the N15 is complicated by the presence of a postauricular muscle
      reflex in some individuals. We attempted an analysis of the N15 wave based on
      distributional characteristics for schizophrenics and control subjects. The
      nature of the N15 wave is described and potential lines of investigation are
      proposed.

PMID- 8138383
TI  - Geriatric nursing versus care of the elderly.

PMID- 8138384
TI  - The elderly patient--does age matter?

PMID- 8138385
TI  - The significance of experimental models of systemic lupus erythematosus and
      antiphospholipid syndrome induced by idiotypic manipulation.
AB  - Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APLS) are two
      related autoimmune conditions. The pathogenesis of the diseases is unclear and
      the etiology is multifactorial. During the last 8 years our laboratory has been
      involved in induction of experimental SLE and APLS both by passive transfer of
      pathogenic antibodies (e.g., anticardiolipin) and by active immunization with
      pathogenic idiotypes. The naive mice, following immunization with Ab1, develop
      anti-autoantibody (Ab2) and eventually anti-autoantibody (Ab3) which has the
      binding capacities of anti-DNA or anticardiolipin. The mice with the
      characteristic syndromes were employed to analyze pathogenic mechanisms and new
      therapeutic modalities.

PMID- 8138386
TI  - The CHAD program for the control of cardiovascular risk factors in a Jerusalem
      community: a 24-year retrospect.
AB  - The CHAD program, a community health program for the control of cardiovascular
      risk factors, was planned in 1969 as an experiment in community-oriented primary
      care (COPC) with the aim of assessing feasibility and effectiveness. The program
      was instituted in a family practice in Jerusalem in 1970, and has provided a
      working demonstration of the integration of community health care with the care
      of individuals and families. Effectiveness was evaluated by comparing changes in
      risk factor status with those in a comparison population. The program was most
      effective with respect to the control of hypertension and cigarette smoking. The
      changes were larger and earlier than those in the comparison population. Positive
      changes were also observed in the comparison population, which was served by a
      primary care clinic that also undertook measures for the control of
      cardiovascular risk factors.

PMID- 8138387
TI  - Oral complications in bone marrow transplantation patients: recent advances.
AB  - This paper presents some of the oral aspects encountered in bone marrow
      transplant (BMT) patients, as reflected in recent research conducted in the
      Department of Oral Medicine. Oral infections caused by Enterobacteriaceae were
      found to be responsible for a large proportion of positive cultures, during
      different stages of the transplantation process. Mucositis was constantly
      detected concomitant with the infections. It correlated with granulocytopenia and
      fever. The mucositis improved together with the immune system reconstitution.
      Immunoglobulins in saliva of BMT patients showed a drastic reduction following
      the patients' conditioning protocol and a return to normal levels soon after the
      transplantation. IgA, IgM and IgG were studied. Saliva was also shown to play an
      important role in the fibrinolytic system, through its plasminogen activator
      inhibitory contents. It seems that the active molecules are contained in the oral
      epithelial cells.

PMID- 8138388
TI  - Changes in the nature of inpatient medical services--impact on medical education
      and patient care.
AB  - One hundred sequential admissions to an internal medicine department in a 765-bed
      teaching hospital in 1973 were compared to 100 admitted in 1987. Mean age in 1973
      was 50.3 years as compared to 57.4 in 1987. Length of stay shortened from 8.8
      days in 1973 to 4.7 days in 1987. The overwhelming majority of the admissions
      during both periods had circulatory and/or respiratory disease. The number of
      diagnoses on admission increased from 2.3 in 1973 to 3.8 in 1987. In 1973, 22% of
      the patients received no drugs as compared to 6.3% in 1987. X-ray studies per
      hospital day doubled and invasive procedures more than quintupled. Intravenous
      fluids were given on 2.5% of days in 1973 and on 22.3% in 1987. Thus medical
      patients are now older and sicker, yet stay for much shorter periods of time.
      This radical change in the intensivity and tempo of work raises serious questions
      about the appropriateness of these sites as major loci for undergraduate
      teaching.

PMID- 8138389
TI  - The terminally ill--secular and Jewish ethical aspects.
AB  - Many ethical, religious, social and legal dilemmas are involved in the care of
      dying patients. Major changes and developments in recent years have greatly
      intensified these moral problems. In this article a comprehensive analysis of the
      relevant principles and practical approaches is offered in order to enhance the
      ability of health care providers to attain morally sound decisions concerning the
      dying patient. The relevant ethical principles include the following: value of
      life, quality of life, nonmaleficence, beneficence, autonomy, paternalism,
      justice, and the physician's integrity. In practical terms, there are three major
      categories: the patient, the treatment and the decision maker. A comparative
      analysis between secular and Jewish attitudes towards the terminally ill patient
      has revealed significant differences both in the fundamental underlying
      principles as well as in the practical solutions to the diverse and difficult
      ethical problems.

PMID- 8138390
TI  - From the laundryman to Lebanon: or how do you tell the parents that their son is
      dying or ... dead?

PMID- 8138391
TI  - Medical research in Israel.

PMID- 8138392
TI  - Serial study of the immune response of an individual with exacerbated simple
      cutaneous leishmaniasis.
AB  - The immunological responses of a patient with exacerbated cutaneous
      leishmaniasis, measured during the course of the disease, are described. Except
      for skin lesions the patient was healthy and showed no signs of
      immunosuppression. Three immunological parameters were measured: specific
      lymphocyte proliferation (LPA), monocyte effector activity (MEA), and antibody
      levels. LPA was positive early in the course of the disease, became negative as
      the lesions enlarged, and was positive again as the lesions healed 28 weeks after
      initiation of the study. In the MEA test, in which the mononuclear cells of the
      patient were incubated in the presence of Leishmania major promastigotes in a 3
      day assay, the number of amastigotes per 100 monocytes remained constant until
      week 28 and then decreased significantly. Antibody levels remained elevated until
      week 28 and then decreased to background levels. The results indicate that the
      cell-mediated immune response parallels the course of the disease while
      circulating antibodies show an inverse relationship.

PMID- 8138393
TI  - Protection of mice against mycobacterial infection by lymphoid cell vaccination.
AB  - Intracellular parasites may thrive by inducing the host's immune system to
      suppress the effector immune response that otherwise limits multiplication. Hosts
      are traditionally immunized with the parasite antigens that induce effector
      immunity. Alternatively, one might vaccinate the host with the host lymphoid
      cells involved in suppression. Multiplication of Mycobacterium marinum was
      prevented by vaccinating mice with cells prepared from the popliteal lymph nodes
      of mice in which the organisms were multiplying logarithmically, that were
      inactivated by fixation with glutaraldehyde. Cells obtained later during
      infection, when the donor mice manifest immunity, did not protect against
      infection. Thus, it may be possible to influence the course of a microbial
      infection by immunizing the host not only with components of the organisms, but
      also with the host components that are exploited by the organism.

PMID- 8138394
TI  - The molecular basis of secondary hyperparathyroidism in chronic renal failure.
AB  - Renal osteodystrophy is a debilitating complication of chronic renal failure and
      secondary hyperparathyroidism (2HPTH) is one of its central features. 2HPTH
      develops as a result of the low levels of serum calcium and 1,25-dihydroxyvitamin
      D [1,25(OH)2D3] and the high serum phosphate that occur in chronic renal failure.
      1,25(OH)2D3 markedly decreases PTH gene transcription and its lack leads to
      2HPTH. A low serum calcium increases PTH mRNA and iPTH levels while a high serum
      calcium has no effect on PTH gene expression. In experimental uremia there are
      increased levels of PTH mRNA. In chronic renal failure there is a shift in the
      calcium set-point to the right. This may be a function of a change in properties
      of the parathyroid cell calcium receptor, which is a G-protein coupled calcium
      sensor.

PMID- 8138395
TI  - Modulation of fetal and placental metabolic pathways in response to maternal
      thyroid and glucocorticoid hormone excess.
AB  - Triiodothyronine (T3) treatment of pregnant rats for 6 days, 10 micrograms/100 g,
      resulted in a pronounced induction of enzymes related to gluconeogenesis and
      lipogenesis and of mitochondrial FAD-glycerophosphate dehydrogenase in the
      maternal liver, as previously observed in male rats. There was virtually no
      change in the activity of these enzymes in the placenta. However, there was a
      distinct induction of these enzymes in the fetal liver, even if increments in
      fetal serum and liver T3 were much smaller than on the maternal side. This
      indicates that changes in hepatic enzyme activities are a more sensitive index of
      fetal hyperthyroidism than T3 levels. The increased lipogenic capacity was
      expressed by greater incorporation of a tritium tracer into fatty acids.
      Administration of triamcinolone, 2 mg/100 g, for the last 5 days of gestation
      resulted in marked induction of maternal hepatic enzymes of lipogenesis,
      gluconeogenesis and of aspartate aminotransferase (ASAT), known to occur in male
      rats, as well as in a metabolic pattern of insulin resistance. The response of
      placental enzymes was limited to a small elevation in ASAT and
      phosphoenolpyruvate carboxykinase (PEPCK) activity. In the fetal liver there was
      no stimulation of lipogenic enzymes, but a marked induction of PEPCK and ASAT.
      The changes in the lipogenic capacity were confirmed by tritium incorporation
      into serum and liver fatty acids. These results demonstrate the marked
      sensitivity of specific fetal enzyme systems to the maternal iatrogenic
      hyperthyroidism or hypercorticism. The limited alterations in placental enzyme
      activities are in accord with the concept that placental metabolic stability
      fulfils a protective function toward the fetus.

PMID- 8138396
TI  - Circulatory disturbance and renal dysfunction in liver disease and in obstructive
      jaundice.
AB  - The appearance of hepatorenal syndrome in a patient with acute or chronic liver
      disease is associated with a dismal outcome. Thus, management of HRS remains a
      formidable challenge to the aggressiveness and perseverance of the physician. The
      best treatment for HRS remains prevention based on avoidance of circulating
      volume contraction or the use of nephrotoxic drugs. Treatment for established HRS
      remains a frustrating experience with recovery being rare. A successful liver
      transplantation is currently the only definitive treatment that can reverse HRS.
      As this procedure is being performed with increasing frequency and encouraging
      results, a new window of hope has been opened for these patients.

PMID- 8138397
TI  - Benign transient hyperphosphatasemia.
AB  - Benign transient hyperphosphatasemia (BTHP) was diagnosed in nine children who
      were examined in the Pediatric Department at Beilinson Medical Center during 2
      years. The characteristic features of this disorder are: a) elevation of serum
      alkaline phosphatase (AP) of 3-50 fold the upper normal value for age, usually
      discovered during mild upper respiratory or gastrointestinal infection, and
      sometimes by routine laboratory workup; b) no clinical or laboratory evidence of
      bone or liver disease; c) the elevated AP is of liver and bone origin; and d) AP
      returns to normal range within 12 weeks. BTHP usually occurs in infants but may
      appear also in adults. Recognition of this benign entity will prevent extensive
      unnecessary laboratory workup.

PMID- 8138398
TI  - Comparative tactile behavior of mothers and fathers with their newborn infants.
AB  - The style with which parents touch their newborn infant was studied. Our method
      was to film mothers and fathers holding their awake infants and to code detailed
      features of their tactile behavior using time-sampling analysis to measure
      frequency of events and continuous event recording to measure duration. The
      results show that both mothers and fathers made tactile contact with their infant
      for an equal amount of time and frequency, but that mothers touch/stroke their
      infants more than they pat/shake them. Fathers did not show any preference for
      either tactile style. Mothers preferentially targeted the infant's hand and face
      more than the body, while fathers preferred to touch the infant's hand. These
      results suggest that mothers' propensity to "caretake" their infants and fathers'
      tendency to play with their infant are reflected in the fine details of their
      parental behavior.

PMID- 8138399
TI  - Diurnal changes in plasma lipoproteins of free-living healthy men consuming a
      standard diet.
AB  - Although it is well established that plasma lipoproteins are involved in
      atherogenesis, most patients with coronary heart disease have normal or nearly
      normal fasting plasma lipid and lipoprotein levels. As most of the human life is
      spent in the fed state we elected to investigate the changes occurring in plasma
      lipids and lipoproteins during normal daily activities. We studied 12 healthy,
      normolipidemic and non-obese subjects on a standard diet divided into three meals
      and three snacks. This method was found to be accurate and reproducible in four
      subjects who underwent repeated studies. The major diurnal changes were observed
      in plasma triglyceride level and in the composition of plasma lipoproteins. The
      degree and pattern of these changes differed among subjects but was specific and
      constant for each individual. The extent of these diurnal changes, which
      correlated positively with fasting plasma triglyceride and inversely with plasma
      HDL2 levels, may play an important role in the pathogenesis of atherosclerosis.

PMID- 8138400
TI  - One-year clinical and echocardiographic follow-up of patients with congestive
      cardiomyopathy treated with captopril compared to placebo.
AB  - The beneficial hemodynamic and clinical effects of angiotensin-converting enzyme
      (ACE) inhibition in patients with severe congestive heart failure has recently
      been documented in large-scale studies. This mode of therapy when added to
      digitalis and diuretics improves survival. To evaluate the clinical effect and
      the changes in cardiac dimensions of captopril compared to placebo we followed 50
      patients with severe congestive heart failure over 1 year using echo-Doppler
      cardiography. After randomization, 25 patients were started on captopril and 25
      patients on placebo. At baseline and at 6 and 12 months, each patient underwent
      exercise tolerance test, radionuclide angiography to estimate left and right
      ventricular ejection fraction, M mode and two-dimensional echocardiography and
      Doppler cardiography to calculate cardiac dimensions and stroke volumes. During
      follow-up two patients in the captopril group and four in the placebo group died.
      Due to clinical deterioration nine patients in the placebo group had to be
      started on open-label captopril. Treatment with captopril was associated with a
      more significant improvement in functional class and exercise duration compared
      to placebo. Forward stroke volume estimated from Doppler echocardiography
      increased significantly by captopril from 47 +/- 3 to 55 +/- 3 ml and decreased
      in the placebo-treated patients from 49 +/- 5 to 44 +/- 4 ml. This improvement
      was associated with a trend towards reduced heart rate by captopril. Left
      ventricular end diastolic volume tended to increase in the placebo group and did
      not change in the captopril group. Calculated mitral regurgitant volume at 6 and
      12 months tended to be lower in the captopril-treated patients. Thus captopril
      therapy proved efficacious in patients with severe congestive heart failure and
      resulted in increased forward stroke volume; it may have a beneficial effect on
      cardiac dimensions and on mitral regurgitation.

PMID- 8138401
TI  - Very early thrombolysis in acute myocardial infarction--a light at the end of the
      tunnel.
AB  - Myocardial damage in acute myocardial infarction is a time-dependent process.
      Thrombolytic therapy effectively opens the coronary artery, restores coronary
      blood flow and prevents ongoing necrosis. We examined the effect of very early
      thrombolytic therapy (including prehospital administration) in a consecutive
      group of 510 patients with myocardial infarction on the following factors:
      mortality, complications and the preservation of left ventricular function. The
      treatment was given to 89 at home (time delay to treatment 1.2 +/- 0.6 h) and 421
      in hospital (2.0 +/- 1.0 h). Twelve patients died in hospital and major
      hemorrhage occurred in 10. The arterial patency rate in 416 patients who
      underwent coronary angiography 6 days later was 82%. Infarct size measured by
      left ventriculography was determined by the area at risk, the delay time until
      the initiation of thrombolytic therapy, the total duration of ischemic pain and
      the degree of restoration of arterial blood flow. We conclude that early
      thrombolytic therapy, particularly prehospital management, is feasible and safe
      and reduces infarct size and mortality. A further decrease in the delay to
      initiation of treatment and more effective thrombolytic therapy will further
      decrease mortality and myocardial damage.

PMID- 8138402
TI  - Transfer kinetics and coefficients of 90Sr, 134Cs, and 137Cs from forage
      contaminated by Chernobyl fallout to milk of cows.
AB  - A experiment was conducted to study kinetics, transfer coefficients, and
      biological half-lives of 90Sr, 134Cs, and 137Cs from feed to milk. A cow was fed
      a diet containing alfalfa hay contaminated by Chernobyl fallout for 14.5 wk. The
      time-dependent activity in milk was approximated by a two-compartment model with
      fast biological half-lives of 2, 0.9, and 1 d and slow biological half-lives of
      36.9, 8.7, and 12.4 d for 90Sr, 134Cs, and 137Cs, respectively. The transfer
      coefficients determined in the experiment were 0.0008 d L-1 for 90Sr, 0.0029 d L
      1 for 134Cs, and 0.0031 d L-1 for 137Cs. The biological elimination phases of
      134Cs and 137Cs were described by a two-compartment model while a one-compartment
      model was proposed for 90Sr.

PMID- 8138403
TI  - Thermoluminescence measurements of gamma-ray doses attributable to fallout from
      the Nevada test site using building bricks as natural dosimeters.
AB  - During the 1950's, the U.S. Government conducted an intensive atmospheric nuclear
      testing program in Nevada. Fallout from these atmospheric tests was measured
      throughout the U.S. with some of the heaviest concentrations to populated areas
      falling east of the test site in Washington County, UT. External exposures from
      6.5 x 10(-4) C kg-1 to 26 x 10(-4) C kg-1 (2.5-5.0 R) were reported for this
      region. This study provides an independent measurement of fallout radiation doses
      to selected communities in Utah using a thermoluminescence technique originally
      developed for the dating of ancient pottery. The application of the predose
      thermoluminescence technique to fallout dosimetry is described. A mean dose of 38
      +/- 15 mGy (4.4 +/- 1.7 R), attributed to fallout radiation, was measured in
      quartz grains extracted from the outer centimeter of bricks removed from six
      communities in Washington and Kane Counties in Utah.

PMID- 8138404
TI  - Long-term clearance of accidentally inhaled 60Co aerosols in humans.
AB  - Long-term body retention was measured in six workers who accidentally inhaled
      60Co aerosols during manipulation with a high-activity 60Co source. Improved
      whole body counting and calibration techniques provided good conditions to follow
      body clearance over 5 y. A two-detector profile scanning arrangement was used to
      measure the activity distribution in vivo over the lung region. The observed
      whole body retention followed a two-exponential time function between 10 and
      1,850 d. Based on the profile measurements, the shorter exponent of 25-78 d was
      associated with activity leaving the pulmonary region while the long-term
      exponential should be interpreted as the clearance of the slowest component of
      the systemic burden with a biological half-time of 500-1,100 d. These
      observations classify the 60Co aerosols encountered in this incident as
      inhalation class W. The agreement of the measured retention pattern with the ICRP
      inhalation model was investigated assuming different aerosol size distributions
      characterized by an activity median aerodynamic diameter = 0.25 micron, 1 micron,
      and 4 microns. It was found that the ICRP model with an activity median
      aerodynamic diameter = 4 microns could describe the retention of our investigated
      cases reasonably well.

PMID- 8138405
TI  - Calibration of a 241Am wound-monitoring system using Monte Carlo techniques.
AB  - Monte Carlo techniques have been used to establish calibration factors and to
      predict gamma spectra for well-defined measurements. These techniques are
      routinely used to predict shielding requirements and critical specifications. The
      Lawrence Livermore National Laboratory is researching the feasibility of using
      Monte Carlo techniques to establish calibration factors for in vivo measurement
      systems. A pilot study was conducted to demonstrate the use of the Monte Carlo
      technique to calibrate in vivo measurement systems, to predict the efficiency of
      a wound measurement system and compare the predicted efficiency with the measured
      efficiency, and to investigate the effects of the source geometry and the
      detector size on the measured efficiency. Results of this study demonstrate good
      agreement between the Monte-Carlo-predicted efficiency and the measured
      efficiency for a wound calibration phantom. The effects of the source geometry
      and the detector size tend to conform to the physical processes that govern the
      measurement process. These results demonstrate that the Monte Carlo technique
      accurately predicts the in vivo measurement efficiency if the characteristics of
      the attenuating material and the Monte Carlo source geometry are properly
      established.

PMID- 8138406
TI  - Distribution of skeletal malignancies in beagles injected with 239Pu citrate.
AB  - The distribution of skeletal malignancies among our beagles injected with 239Pu
      as young adults roughly seems to follow the distribution of skeletal mass and
      skeletal 239Pu. These findings are similar to those we reported previously for a
      group of dogs given 26Ra. Although there were differences in tumor distribution
      between the animals given 226Ra and those given 239Pu, most of them were not
      statistically significant; however, the radium dogs seemed to show a greater
      sensitivity to bone tumor origin in the tibia, while there may have been a
      tendency among the plutonium dogs toward increased relative sensitivity in the
      scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site
      for the formation of naturally-occurring bone malignancy in the dog is the distal
      radius. Perhaps there were too few tumors and too few dogs to establish
      statistical significance. A correlation between tumor location and at least two
      anatomical-physiological factors in the skeleton indicated that these two factors
      (site-specific bone turnover rate and percent of red marrow at the site, which is
      correlated with vascularity) may influence the appearance of malignancies both
      individually and in combination. Except for the femur, there appeared to be no
      difference between the relative distribution of skeletal malignancies of low
      level (30 Bq-2 Bq kg-1 injected) and high-level (3-122 kBq kg-1) dogs.
      Distribution of bone tumors between the axial and appendicular skeleton was 50%
      vs. 50% for 239Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and
      35, respectively) for dogs given 226Ra. This difference was not significant (p >
      0.2).

PMID- 8138407
TI  - Probabilistic laser safety: ocular damage models for Q-switched neodymium and
      ruby lasers.
AB  - International standards for the protection of the eyes from the hazards of laser
      radiation define a nominal ocular hazard distance as a distance beyond which an
      individual would not be expected to suffer any adverse biological effects. The
      nominal ocular hazard distance, and any associated hazard zones, are calculated
      using a deterministic technique. This technique does not consider the likelihood
      that an eye will be irradiated, or the probability that if any eye is exposed,
      then some level of ocular damage will result. An alternative method of hazard
      assessment, without compromising safety, is to adopt a probabilistic approach in
      which the ultimate safety criterion is that the expectation of someone receiving
      ocular damage must be less than some acceptable risk level. An important element
      in this assessment is an ocular damage model, which predicts the probability with
      which a laser exposure will cause permanent eye damage. This paper describes a
      rationale for the use of the minimum ophthalmoscopically visible lesion as a
      threshold criterion for the development of ocular damage models. A brief review
      of existing ocular damage threshold data for Q-switched neodymium:YAG and ruby
      lasers is presented, and ocular damage models for these lasers systems are
      derived.

PMID- 8138408
TI  - Dynamic behavior of 110mAg in sheep tissues.
AB  - The transfer coefficient of 110mAg to a range of sheep tissues and its biological
      half-life in these tissues has been determined. Liver was shown to be the major
      site of 110mAg deposition and retention, with a transfer coefficient of Ff 7.1 d
      kg-1 and a biological half-life of 79 d. These results also suggest that previous
      estimates of the transfer of silver to muscle were too high, although further
      work would be required to confirm this. There is a need for accurate data which
      can be used to predict the transfer of 110mAg to food-producing animals.

PMID- 8138409
TI  - Influence of ventilation strategies on indoor radon concentrations based on a
      semiempirical model for Florida-style houses.
AB  - Measurements in a full-scale experimental facility are used to benchmark a
      semiempirical model for predicting indoor radon concentrations for Florida-style
      houses built using slab-on-grade construction. The model is developed to provide
      time-averaged indoor radon concentrations from quantitative relationships between
      the time-dependent radon entry and elimination mechanisms that have been
      demonstrated to be important for this style of residential construction. The
      model successfully predicts indoor radon concentrations in the research structure
      for several pressure and ventilation conditions. Parametric studies using the
      model illustrate how different ventilation strategies affect indoor radon
      concentrations. It is demonstrated that increasing house ventilation rates by
      increasing the effective leakage area of the house shell does not reduce indoor
      radon concentrations as effectively as increasing house ventilation rates by
      controlled duct ventilation associated with the heating, ventilating, and air
      conditioning system. The latter strategy provides the potential to minimize
      indoor radon concentrations while providing positive control over the quality of
      infiltration air.

PMID- 8138410
TI  - Radon in outdoor air in Nevada.
AB  - Measurements of radon at 50 sites with varying geology indicate that outdoor air
      in Nevada is comparable to that measured nationwide by Hopper et al. (1991). The
      statewide median of 15 Bq m-3 (0.4 pCi L-1) is essentially the same as the
      nationwide median. The range is considerable: from 2.6-52 Bq m-3 (0.07-1.40 pCi L
      1). Variations in these measurements can generally be correlated with different
      concentrations of radon in soils and uranium and its progeny in rocks. Silica
      rich igneous rocks (rhyolites and granites) appear to be the main sources of high
      levels of radon in outdoor air in Nevada. Concentrations of radon in outdoor air
      generally correlate with levels of radon in soil gas. Measurements taken from
      heights of 0.5, 1.0, and 2.0 m above the ground suggest that radon in outdoor air
      reflects the local geology throughout this range of heights. Towns for which >
      20% of the homes have indoor-air radon concentrations > 48 Bq m-3 (4 pCi L-1)
      generally have relatively high soil-gas radon, relatively high outdoor-air radon,
      or both.

PMID- 8138411
TI  - Radiocesium in children from Belarus.
AB  - The body burdens of 137Cs were measured in 74 children from Belarus who had been
      exposed to fallout from the Chernobyl accident. The children were between the
      ages of 8 and 12 y old and were visiting the Ottawa area during the summers of
      1991 and 1992. The body burdens varied from 0.04-2.25 kBq, which are less than or
      comparable to the amount of natural 40K in the children's bodies. There was no
      apparent dependence on age or sex. The body burdens were related, to some extent,
      with recorded fallout levels in the region of origin but did not appear to change
      significantly from 1991 to 1992. During their stay in Canada, radiocesium was
      being cleared from the children's bodies with a mean half-time of 33 d (range =
      12-77 d). The highest intake rate of 137Cs was estimated to be 18 Bq d-1 and the
      highest dose rate was 0.13 mSv y-1.

PMID- 8138412
TI  - Statistical analysis of radioactive contamination levels in settlements of the
      Chernobyl middle zone.
AB  - A statistical analysis of the measurements of 137Cs activity density carried out
      in 1990-1991 in 30 settlements of the mesozone (and partially in the nearest
      zone) of the Chernobyl nuclear power plant is presented. It is shown that the
      mean activity density of radionuclides is close to 14 Bq cm-2 for the inspected
      settlements of Byelorussia which is significantly less than that for the
      inspected settlements of the nearest zone (48 Bq cm-2). The analysis shows that
      there is a near linear correlation between rms deviation of activity density and
      its mean value. It is also shown that the correlation radius of the data is
      comparable with the spatial step of the measurements and that the activity
      density distribution is reasonably described in terms of a normal distribution.

PMID- 8138413
TI  - Silicosis and lung cancer risk in underground uranium miners.
AB  - The presence of radiographic silicosis as a risk factor for lung cancer was
      assessed in a case-control study conducted within a study cohort of New Mexico
      underground uranium miners. Chest radiographs were interpreted for the presence
      of silicosis for 65 lung cancer cases and 216 controls. The presence of silicosis
      on the chest radiograph taken closest to the start of employment or on the latest
      radiograph available was not associated with lung cancer risk after adjustment
      for cumulative exposure to radon progeny. The odds ratio associated with the
      presence of any type of opacity indicative of pneumoconiosis on the chest x ray
      closest to the start of employment was 1.33 (95% confidence interval, 0.31-5.72).
      For the most recent available chest x ray, the corresponding odds ratio was 1.16
      (95% confidence interval, 0.35-3.84). Although the findings are limited by the
      relatively small number of subjects, the lack of association of silicosis with
      lung cancer suggests that silica exposure should not be regarded as a major
      uncertainty in extrapolating radon risk estimates from miners to the general
      population.

PMID- 8138414
TI  - The updated BESGE spectrometer for pure beta activities in environmental
      matrices.
AB  - This work describes an updated version of a beta spectrometer that measures pure
      beta emitter activities. The detection system consists of a plastic scintillator
      surrounded in a 4 pi geometry by large anticoincidence NaI(Tl) scintillators. A
      thin silicon detector, inserted between the plastic and the sample, helps to
      reduce the gamma background. A Monte Carlo code, used to calculate the quite
      complex spectrometer response function to any isotope, is also described.

PMID- 8138415
TI  - Experimental evaluation of wire mesh screen counting parameters for measurements
      of the unattached fraction of radon progeny.
AB  - Direct measurements (specifically the front-to-back ratio) of alpha radioactivity
      from radon progeny deposited on the front and back of a 400-wire mesh screen were
      performed under realistic aerosol conditions outdoors with two scintillation
      alpha detectors facing both sides of the screen simultaneously. Two flow regimes
      were tested: one which kept the flow Reynolds number (Ref) for the wire below one
      (200 L min-1) and a second with the flow Reynolds number for wire > 1 (400 L min
      1). To estimate the radioactivity loss in the screen, parallel measurements of
      open and backup filters were also performed. The average front-to-back ratio
      expressed as a ratio of the potential alpha energy concentration as measured on
      the screen side facing the airflow to the other side of the screen for 200 L min
      1 and 400 L min-1 was 3.42 +/- 0.32 (standard error) and 2.30 +/- 0.14 (standard
      error), respectively. The loss of radioactivity in the screen expressed as a
      ratio between the potential alpha energy concentration measured on an open filter
      minus backup filter to the sum of the potential alpha energy concentration
      measured on the front and back of the screen was 1.29 +/- 0.13 and 1.27 +/- 0.22
      for 200 and 400 L min-1, respectively.

PMID- 8138416
TI  - Safety considerations and recommendations for analytical x-ray devices from a
      review of survey data.
AB  - Survey data on analytical x-ray devices were reviewed to provide an overview of
      safety problems. It was found that old equipment with one or more safety
      deficiencies is being used in many research laboratories and that predictions of
      long-term risks are difficult. Assessment of the problems against recently
      revised radiation risks in BEIR V (NAS 1990) and occupational dose equivalent
      limits in ICRP Publication 60 (1991), together with reasonable extrapolations and
      safety considerations, suggest that improvements in several areas are necessary
      in order to prevent or reduce potentially adverse health effects. Certain
      recommendations are, therefore, proposed: the annual occupational limit of 500
      mSv to the hands and the skin as recommended by the ICRP (1991) should still
      apply; however, estimates of the bone dose should account for the differential
      absorption between bone and soft tissue at the low-energy photons encountered in
      analytical x-ray operations; general guidance to improve safety of old equipment
      and open-beam devices should be made available; user education and instruction
      need improvement on specific issues; and survey methods need revision and
      updating.

PMID- 8138417
TI  - Implication vs. causation: epidemiological data needed for true association or
      causation.

PMID- 8138418
TI  - DNA vaccination. A clue to memory?

PMID- 8138419
TI  - Genetic predetermination of quantitative expression of HLA antigens in platelets
      and mononuclear leukocytes.
AB  - In view of the potential functional importance of quantitative expression of HLA
      antigens, a series of studies were conducted to determine the relative quantities
      of specific HLA-A and -B antigens expressed in MNLs and platelets of HLA
      phenotyped family members and unrelated individuals. An mAb that reacts with a
      well-defined monomorphic epitope in the alpha 3 domain of the heavy chains of HLA
      molecules was developed and used to quantify each HLA-A or -B antigen on western
      blots of IEF gels. The results of these studies demonstrated that the relative
      quantities of HLA-A and -B antigens in platelets and MNLs of an individual did
      not change over time. Further studies showed that the relative quantities of HLA
      A and -B antigens for haplotypes shared among first-degree relatives were always
      the same and followed Mendelian inheritance. In contrast, the relative quantities
      of HLA-A and -B antigens for a haplotype shared by unrelated individuals varied
      significantly. All these findings support the hypothesis that the quantitative
      expression of HLA antigens is genetically predetermined and may play important
      roles in determining disease susceptibility and severity.

PMID- 8138420
TI  - HLA class II molecules transduce accessory signals affecting the CD3 but not the
      interleukin-2 activation pathway in T blasts.
AB  - MHC class II molecules play a central role in the control of the immune response,
      but their biologic function and mechanism of action on the surface of activated
      human T lymphocytes are not entirely understood. In our study, the functional
      role of HLA class II molecules in T-blast proliferation was investigated by
      analyzing in parallel the IL-2- and CD3-driven activation pathways. The results
      indicate that the cross-linking of class II and CD3 molecules significantly
      increased the CD3-mediated T-blast proliferation, while no effect was observed on
      the IL-2-driven cell activation. This phenomenon was not confined to either CD4+
      or CD8+ subsets nor was specifically affected by CD45 triggering. Biochemical
      studies showed that signaling via MHC class II molecules in T blasts led to PKC
      membrane translocation and IP accumulation. The simultaneous triggering of CD3
      and HLA class II molecules led to a synergistic effect on IP accumulation but did
      not increase the CD3-mediated PKC membrane translocation. Our data suggest that
      HLA class II molecules are involved in T-cell-T-cell interactions and can mediate
      accessory signals, affecting the T-lymphocyte activation state.

PMID- 8138421
TI  - Microheterogeneity in HLA-B35 alleles influences peptide-dependent
      allorecognition by cytotoxic T cells but not binding of a peptide-restricted
      monoclonal antibody.
AB  - Strong peptide dependency of HLA-B*3501-specific alloreactive T-cell clones was
      observed in the recognition of cells bearing closely related B35 variants. The
      single amino acid exchange in the beta-pleated sheet of B*3503 completely
      abolished the responses of all clones, whereas an amino acid exchange in the
      alpha 2 helix of the newest B35 member (B*3508) only altered allorecognition of
      one T-cell clone, demonstrating the differential impact of these positions on
      peptide binding to B35 molecules. In contrast to T cells, a mAb (TU165)
      recognizing the B35 specificity in a peptide-dependent manner bound to the B35
      variants irrespective of their sequence heterogeneity. However, quantitative
      binding differences were detected with cells bearing the same B35 alleles. This
      is most likely due to variations in the amount of peptide(s) that associates with
      B35 and forms the ligand seen by this mAb. These results reveal how naturally
      occurring single amino acid substitutions have led to generation of functionally
      distinct molecules of another multimember HLA class I cluster.

PMID- 8138422
TI  - Celiac disease among Ashkenazi Jews from Israel. A study of the HLA class II
      alleles and their associations with disease susceptibility.
AB  - The immunogenetics of celiac disease demonstrates a highly significant
      association with the HLA class II alleles DQA1*0501 DQB1*0201 encoded in either a
      cis- or trans-configuration. In Northern Europe, these alleles are found in
      linkage disequilibrium with DRB1*0301 while in Southern Europe an additional
      secondary association through linkage disequilibrium is seen with the combination
      DRB1*1101/0701. This study examines 34 Ashkenazi Jews with celiac disease and 36
      ethnically matched controls to determine alleles at the DRB, DQA1, DQB1, and DPB1
      loci using SSO probes in conjunction with gene amplification by the PCR. The
      results confirm a highly significant association with the DQA1*0501 DQB1*0201
      allelic combination (71% celiac vs 8% control individuals; p = 0.00005; chi 2 =
      21.4). Of celiac subjects, 29% were negative for the proposed DQ susceptibility
      alleles, the majority of whom were DRB1*0402 positive (20% overall celiac group).
      No additional susceptibility was associated at the DRB3 and DPB loci. This study
      confirms that the MHC-linked celiac disease susceptibility among Ashkenazi Jews
      is closely associated with the presence of the combination of alleles DQA1*0501
      DQB1*0201. However, within this population of relatively high-prevalence celiac
      disease, 30% of celiac patients do not carry these alleles and are therefore not
      covered by a single "unifying" hypothesis.

PMID- 8138423
TI  - High-resolution HLA-DPB typing based upon computerized analysis of data obtained
      by fluorescent sequencing of the amplified polymorphic exon 2.
AB  - To differentiate 32 HLA-DPB alleles, conventional techniques such as serology and
      cellular typing are inadequate for high-resolution DPB typing. The most refined
      DNA typing until now is SSO typing and new selected oligonucleotides can be added
      to this system to distinguish new allele sequences. DNA sequencing, however,
      reveals directly the sequence information of all polymorphic HVRs and has the
      advantage of being independent from exon polymorphisms. We have developed a new
      DNA-based typing approach that is rapid, fully automated, and therefore suitable
      for routine typing. The system is based upon direct sequencing of amplified DNA
      with fluorescent-labeled primers. The designation of alleles is obtained by a
      comparison of all polymorphic positions in the determined sequence with all known
      allele sequences retained in a database along with their heterozygous
      combinations. Sequence data at both constant and polymorphic positions are used
      for quality control. In this study, the typing results of a panel of 91 previous
      SSO-typed DNA samples are described. After comparison with the SSO-typing
      results, we conclude that with this SBT system allele assignment is reliable. The
      method is easy to perform since both sequencing and assignment are automated.
      Furthermore, the system is easily applicable to other gene systems.

PMID- 8138424
TI  - HLA-DQ2 second-domain polymorphisms may explain increased trans-associated risk
      in celiac disease and dermatitis herpetiformis.
AB  - Sequence polymorphism in the DQ2 beta chain was investigated in 80 Caucasoid
      patients with CD, 23 patients with DH, and 64 healthy controls. A set of
      amplification primers were designed to amplify a 281-bp region between amino
      acids 95 and 135 encoding the second domain of the DQ beta chain gene. A
      polymorphism at amino acid 135 was shown to distinguish DR3 and DR7 haplotypes.
      Two SSO probes were designed to identify amino acid sequences (133-135) RND (DR3
      DQ2) and RNG (DR7-DQ2). To establish whether polymorphism existed elsewhere in
      the second-domain sequence, which could explain the migratory characteristics of
      the CD-associated DR3-DQ2 beta-chain reported by Roep et al. DQB1 second-domain
      PCR products were sequenced from the genomic DNA of three CD patients. The
      results showed that the polymorphism at amino acid 135 distinguishing DR3 and DR7
      haplotypes was present in CD, DH patients, or normal controls of the appropriate
      DR and DQ genotypes by oligonucleotide hybridization. Cloning and sequencing of
      DQB1 second domains of three CD patients (two DR3,3 and one DR3,7) gave normal
      sequences expected from their genotypes. No specific polymorphism of DQB1 second
      domains on CD-associated DR3 haplotypes distinguishes them from normal DR3
      haplotypes. We conclude that individuals positive for the DR3,7 genotype have the
      potential to express a unique trans-encoded heterodimer with enhanced ability to
      predispose people to CD.

PMID- 8138425
TI  - Fine tuning of linear accelerator accessories for stereotactic radiotherapy.
AB  - PURPOSE: Experience with the University of Wisconsin's stereotactic radiotherapy
      (SRT) accessory system was applied to build a new system, facilitate alignment of
      linac photon beams with a Brown-Roberts-Wells (BRW) stereotaxy, and increase the
      versatility and stability of the stereotaxy. METHODS AND MATERIALS: High tensile
      strength stainless steel was used in the floor stand to increase the range of
      gantry rotation relative to ranges allowed by truss-mounted stands. The
      collimator assembly and floor stand were each fitted with two-axis gimbal and
      translation adjustments in addition to the floor stand's three-axis adjustments.
      The head ring positioning assembly was fitted with two braces to prevent the head
      ring from deforming with patient motion. Six MV linac photon beam characteristics
      were measured with a computer-controlled scanning system and a diode in water, at
      source to surface distances (SSD) of 80 and 100 cm, and for 13 divergent
      collimators ranging in diameter from 1-4 cm at 100 cm SSD. Quality assurance
      software was applied to screen data for questionable consistency or symmetry.
      Integrity of the stereotaxy was evaluated with target simulation films and
      repeated measurements which were part of the quality assurance of clinical
      treatments. A method was developed using a glass etched contact reticle to obtain
      average simulated target to beam center distances (delta av) from target
      simulation films. RESULTS AND CONCLUSION: New aspects of the current system have
      improved the ability to fine tune and analyze stereotactic alignment. Beam
      characteristics met stringent output criteria and penumbral widths were the same
      or narrower than penumbral widths reported elsewhere. The precision of measuring
      delta av was 0.1 mm, and delta av averaged over 50 target simulation films was
      0.7 +/- 0.1 mm. Results suggest that it may be useful to determine delta av from
      target simulation films with the method described here.

PMID- 8138426
TI  - Retrospective reconstruction of three-dimensional radiotherapy treatment plans of
      the thorax from two dimensional planning data.
AB  - PURPOSE: A method for the retrospective reconstruction of three-dimensional (3-D)
      radiotherapy treatment plans from two-dimensional (2-D) planning data is detailed
      in this paper. METHODS AND MATERIALS: With these techniques the user can register
      an arbitrarily shaped portal on a simulation film with a diagnostic computed
      tomography study of the patient and then generate the resultant 3-D dose
      distribution or dose-volume histogram. Seven treatment plans were reconstructed
      of patients who had previously undergone 3-D treatment planning for fields
      involving the thorax and who had had a diagnostic computed tomography (CT) scan.
      The dose-volume histograms and the spatial positions of the beams on the
      reconstructed plans were then compared to those of the original 3-D plan, which
      until then, were not made available to the investigators. RESULTS: The dose
      volume histograms of the reconstructed plans did not differ from those of the
      original plans by more than 3% except in the low dose region. The error in
      positioning the beam in the reconstructed plan was determined to be approximately
      5 mm. CONCLUSION: The technique of 3-D treatment plan reconstruction can be used,
      through retrospective studies, to obtain better assessments of normal tissue
      complication probabilities and tumor control probabilities.

PMID- 8138427
TI  - Clinical use of on-line portal imaging for daily patient treatment verification.
AB  - PURPOSE: To determine the ease of use by clinical staff and reliability of an
      electronic portal imaging system and evaluate the potential to utilize on-line
      imaging to assess accuracy of daily patient treatment positioning in radiation
      therapy. METHODS AND MATERIALS: A computer controlled fluorescent screen-mirror
      imaging system was used to acquire on-line portal images. A physician panel
      assessed on-line image quality relative to standard portal film. Clinical use of
      the imager was implemented through a protocol where images were obtained during
      the first six monitor units of external beam. The images were visually compared
      to a reference portal and patient setup was adjusted for errors exceeding 5 mm.
      Subsequent off-line analysis was utilized to give insight into the magnitude of
      clinical setup error in the visually accepted images. RESULTS: Physician
      evaluation of on-line image quality with an initial 211 images found that 70%
      were comparable or superior to standard film portal images. Eighty percent of
      treatment fields fit completely within the on-line imaging area. Eight percent of
      on-line images were rejected due to poor image quality. Twelve percent of the
      daily treatment setups imaged required adjustment overall, but specific field
      types predictably required more frequent adjustment (pelvic and mantle fields).
      Off-line analysis of accepted images demonstrates that 18% of the final images
      had setup errors exceeding 5 mm. CONCLUSION: On-line imaging facilitated daily
      portal alignment and verification. Ease of use, almost instantaneous viewing and
      consistent ability to identify and locate anatomical landmarks imply the
      potential for on-line imaging to replace film based approaches. Retrospective
      analysis of daily images reveals that visual assessment of setup is not
      sufficient for eliminating localization errors. Further improvement is required
      with respect to detecting localization error and fully encompassing larger field
      sizes.

PMID- 8138428
TI  - A clinically practical electron cone for the treatment of head and neck cancer.
AB  - PURPOSE: The purpose of the work was to develop a practical electron cone and to
      compare its dosimetry with that of the conventional applicator collimation
      system. METHODS AND MATERIALS: The electron cone consists of the upper part of a
      manufacturer-supplied electron applicator and an institution-built rectangular
      extension tube which produces a 12 cm x 6 cm field at 100 cm SSD while
      maintaining an air gap of 5 cm between the patient. RESULTS: The compact size of
      the cone allows electron irradiation without having to reposition the patient
      after photon treatment. The radiation field is very similar to that of a standard
      15 cm x 15 cm applicator with a 12 cm x 6 cm field restricting insert. Radiation
      leakage at the surface of the special cone is typically less than 1% of the
      useful beam at dmax. During 12 years of clinical use the special cone proved
      itself very practical in the treatment of more than 300 patients. CONCLUSION: An
      electron cone practical for clinical use with dosimetry comparable to the
      conventional applicator was developed.

PMID- 8138429
TI  - Stereotactic radiotherapy of intracranial tumors--an ideal candidate for
      accelerated treatment.

PMID- 8138430
TI  - Progress in the evaluation of electronic portal imaging--taking one step at a
      time.

PMID- 8138431
TI  - A multi-institutional experience with stereotactic radiosurgery for solitary
      brain metastasis.
AB  - PURPOSE: A multi-institutional experience in radiosurgery for solitary brain
      metastases was combined to identify factors associated with safety, efficacy,
      tumor control, and survival. MATERIALS AND METHODS: A review of 116 patients with
      solitary brain metastases who underwent gamma knife stereotactic radiosurgery at
      five institutions was performed. The median follow-up was 7 months following
      radiosurgery and 12 months following diagnosis. Minimum tumor doses varied from 8
      30 Gy (mean, 17.5 Gy). Forty-five patients failed prior radiotherapy and 71 had
      no prior brain irradiation. Fifty-one patients had radiosurgery alone and 65
      underwent combined radiosurgery with fractionated large-field radiotherapy (mean
      dose, 33.8 Gy). RESULTS: Median survival was 11 months after radiosurgery and 20
      months after diagnosis. Follow-up documented local tumor control in 99 patients
      (85%), tumor recurrence in 17 (15%), and documented radiation necrosis in one
      (1%). The 2-year actuarial tumor control rate was 67 +/- 8%. Tumor histology
      affected survival (better for breast cancer, p = .004) and local control (better
      for melanoma and renal cell, p = .0003) in multivariate analyses. Combined
      fractionated radiotherapy and radiosurgery improved local control (p = 0.111),
      but not survival in multivariate testing. CONCLUSION: Radiosurgery is effective
      in controlling solitary brain metastases with low morbidity. Further study is
      needed to better define optimum treatment parameters for radiosurgery.

PMID- 8138432
TI  - Linear accelerator-based stereotactic radiosurgery for acoustic schwannomas.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) is currently being investigated for
      treatment of acoustic schwannomas in patients who are not good surgical
      candidates. The vast majority of the available data is based on gamma knife
      treated patients. We present the largest series of patients treated with linear
      accelerator-based SRS. METHODS AND MATERIALS: Thirty-two patients with acoustic
      schwannomas were treated with SRS between July 1988 and February 1993; follow-up
      ranged from 4-59 months. Age ranged from 34-88 years (mean, 62 years). The
      primary presenting symptom was hearing loss in 30 patients and dementia in two
      patients. Indications for SRS were age > 65 years (17 patients); recurrence after
      surgery (13 patients); and medical infirmity (two patients). Dose to the
      periphery of the lesion ranged from 10-22.5 Gy (mean, 15.5 Gy) specified at the
      68-90% isodose line (mean, 80%). Collimator size ranged from 12-35 mm (mean, 23
      mm), indicating that the sizes of the tumors were significantly larger than those
      reported in most gamma knife series. RESULTS: Follow-up magnetic resonance
      imaging (MRI) and/or computed tomography (CT) scans revealed the following at 1
      year: tumor regression, 12 patients (63%); and no change, seven patients (37%).
      At 2 years, 11 tumors (73%) were smaller and four tumors (27%) were unchanged. At
      3 years, seven patients (78%) had experienced tumor regression and two (22%) had
      no change. No patient experienced tumor progression after SRS. Seven patients
      (22%) suffered one or more treatment complications: new onset of 5th and/or 7th
      cranial nerve deficit (six patients), ataxia (two patients), and/or hydrocephalus
      necessitating VP shunt (two patients). CONCLUSION: Linear accelerator-based SRS
      provides excellent short-term local control and a relatively low incidence of
      complications for acoustic schwannomas. Our data compare favorably with results
      obtained with gamma knife-based SRS. Additional follow-up will be necessary to
      evaluate the long-term results of treatment.

PMID- 8138433
TI  - Technical factors affecting morbidity in definitive irradiation for localized
      carcinoma of the prostate.
AB  - PURPOSE: The impact of some technical factors on morbidity was analyzed in 738
      patients with histologically confirmed carcinoma of the prostate treated with
      definitive irradiation. METHODS AND MATERIALS: The records of all patients were
      reviewed, and morbidity of irradiation was evaluated according to severity. All
      patients were followed up for a minimum of 3 years (median observation, 6.5
      years). RESULTS: The most frequent Grade 2 (moderate) intestinal complication was
      proctitis, which was observed in 5% of the patients, followed by enteritis (1%)
      and anal-rectal fibrosis or stricture (about 1%). Incidence of Grade 3 (severe)
      proctitis was less than 1% and small bowel obstruction, 0.2%. One patient
      developed radiation-induced ileitis complicated with peritonitis, which was
      fatal. The most frequent Grade 2 urinary complication was urethral stricture (5%)
      and cystitis with significant symptoms or hematuria (2%). A vesicosigmoid and a
      rectovesical fistula (.4%) were noted, which required colostomy. One patient with
      hemorrhagic cystitis (.2%) required an ileal bladder, and two cases of ureteral
      stricture (.3%) required surgical correction. Most cases of Grade 2-3 intestinal
      or urinary morbidity appeared within 2-5 years after therapy (8% moderate and 3%
      severe cumulative intestinal morbidity at 10 years, and 9% and 3%, urinary). The
      actuarial incidence of rectosigmoid Grade 2 and 3 morbidity was 10% for patients
      treated to the pelvic lymph nodes and the prostate and 3% for those treated to
      the prostate only (p = 0.04). The difference in urinary morbidity in these two
      groups of patients was not statistically significant. There was also no
      significant correlation of morbidity with boost portal size for prostate
      irradiation. Patients treated with a stationary portal technique that delivered
      higher doses to the urinary bladder had a significantly greater incidence of
      urinary morbidity (18% cumulative) compared with patients treated with rotational
      techniques (5%) (p < 0.1). However, patients treated with pelvic fields and
      rotational techniques had a higher intestinal and rectosigmoid morbidity (11%)
      than patients treated to the prostate only (< or = 5%) (p = 0.05). No
      statistically significant difference in intestinal or urinary morbidity was
      related to doses of irradiation (60-70 Gy). CONCLUSION: Volume treated and, to a
      lesser extent, dose of irradiation at tolerance levels are important factors
      influencing significant morbidity in patients with carcinoma of the prostate
      treated with definitive irradiation. With recent advances in three-dimensional (3
      D) treatment planning and conformal radiation therapy techniques, it is
      imperative to precisely determine optimal volumes and doses of irradiation
      required to achieve the highest local-pelvic tumor control while minimizing
      morbidity to enhance the role of irradiation in the management of localized
      carcinoma of the prostate.

PMID- 8138434
TI  - The prognostic significance of DNA ploidy in clinically localized prostate cancer
      treated with radiation therapy.
AB  - PURPOSE: To determine the prognostic significance of deoxyribonucleic acid (DNA)
      ploidy in comparison to pretreatment prostate specific antigen (PSA) and other
      prognostic factors for patients with adenocarcinoma of the prostate treated with
      external beam radiotherapy. METHODS AND MATERIALS: Paraffin-embedded prostatic
      adenocarcinoma material was obtained from patients treated from 1987-1991.
      Sufficient histologic material for flow cytometric DNA content analysis was
      obtained from 86 patients and adequate histograms were obtained from 76 of these.
      The DNA histogram profiles were classified as diploid, tetraploid, or aneuploid.
      Median patient follow-up was 36 months. RESULTS: There were 54 patients with
      diploid tumors, and 22 with nondiploid tumors (11 tetraploid and 11 aneuploid).
      Since the disease outcome for tetraploid and aneuploid tumors was the same, these
      were pooled (nondiploid tumors). The distribution of diploidy and nondiploidy
      correlated with pretreatment PSA (p < 0.0005) and grade (p = 0.055), but not with
      stage, pretreatment prostatic acid phosphatase, transurethral resection,
      pretreatment serum testosterone, or age. In actuarial univariate analyses, DNA
      ploidy was a significant predictor of outcome for local failure, distant
      metastases, any clinical relapse, rising PSA, and rising PSA and/or relapse.
      Ploidy was not a significant predictor of overall survival, although there were
      only six deaths. Diploidy predicted for improved outcome, for example, 34.6%
      incidence of a rising PSA and/or relapse at 4 years compared to 76.9% with
      nondiploidy (p < 0.0001). An actuarial univariate analysis of other potential
      prognostic factors using the composite endpoint of rising PSA and/or relapse also
      revealed pretreatment PSA, grade, pretreatment prostatic acid phosphatase, stage,
      and serum testosterone to be significant predictors of outcome. In Cox
      proportional hazards analysis, pretreatment PSA, DNA ploidy, and grade were the
      only independent prognostic factors for disease outcome using the composite
      endpoint. CONCLUSION: DNA ploidy is an independent predictor of outcome in
      patients with Stages T1-T3 prostate cancer treated with definitive external beam
      radiotherapy.

PMID- 8138435
TI  - Impact of non-CTCL dermatologic diagnoses and adjuvant therapies on cutaneous T
      cell lymphoma patients treated with total skin electron beam radiation therapy.
AB  - PURPOSE: To evaluate the impact of pre-cutaneous T-cell lymphoma dermatologic
      diagnoses and adjuvant therapies on the relapse-free and overall survivals of
      patients treated with total skin electron beam therapy. METHODS AND MATERIALS:
      Between 1974 and 1990, 164 patients were evaluated by members of Yale University
      School of Medicine departments of Dermatology and Therapeutic Radiology and
      treated with total skin electron beam therapy to a total dose of 3600 cGy.
      Patients who achieved a clinical complete response were offered
      doxorubicin/cyclophosphamide chemotherapy, extracorporeal photopheresis, or no
      systemic adjuvant therapy. The effects of TNM stage, antecedent non-T-cell
      lymphoma dermatologic diagnoses, and systemic adjuvant therapies were analyzed
      for their impact on relapse-free and overall survival. RESULTS: In this cohort of
      patients, an antecedent dermatologic diagnosis of follicular mucinosis or
      lymphomatoid papulosis was significantly associated with a shorter relapse-free
      survival for T1 and T2 patients, while antecedent "non-specific" dermatitides
      were associated with a somewhat better relapse-free survival. When the impact of
      systemic adjuvant therapies was analyzed, neither systemic
      doxorubicin/cyclophosphamide chemotherapy nor systemic extracorporeal
      photopheresis were found to delay cutaneous relapse. CONCLUSION: Our results
      suggest that antecedent follicular mucinosis and lymphomatoid papulosis may be
      associated with short relapse-free survival in T1 and T2 patients treated with
      total skin electron beam therapy. They also imply that neither adjuvant
      chemotherapy nor extracorporeal photopheresis delay cutaneous relapse after total
      skin electron beam therapy.

PMID- 8138436
TI  - Prognosis with newly diagnosed mycosis fungoides after total skin electron
      radiation of 30 or 35 GY.
AB  - PURPOSE: To determine the prognosis of new patients with T1-4N0-1B0M0 mycosis
      fungoides treated with total skin electron beam radiation. METHODS AND MATERIALS:
      25 consecutive patients received 30 Gy with 3 or 4 MeV electrons in 1977-1980;
      121 received 35 Gy with 4 MeV in 1980-1992. Response rates, relapse-free
      survival, and overall and cause-specific survivals were assessed by explicit
      criteria. The relationships of T, N, gender, age, and radiation technique to
      prognosis were investigated by regression statistics. RESULTS: The average age
      was 55 years and the male:female ratio was 1:4. Forty-four percent were T1N0 and
      34% were T2N0. The overall complete response rate was 82%, and lower T status,
      more radiation, and female gender were independently and positively associated
      with response. Median follow-up was 5.2 years. T1 patients who entered remission
      had a higher relapse-free survival compared to T2 through T4 patients. Thirty
      four percent of T1 patients remained relapse-free at 6 years, compared to fewer
      than 20% of T2-4 patients. For all 146 patients the median overall survival was
      not reached at 15 years. Only 8 of 29 deaths were related to mycosis fungoides
      and these were significantly associated with higher T. The 54 T1N0 patients who
      had 35 Gy had a 10-year mycosis fungoides-specific survival of 100%. CONCLUSION:
      Total skin electron beam radiation gives good results with T1N0B0M0 disease. T3-4
      disease is less likely to respond, it relapses more quickly, and it implies a
      poorer survival, but radiation offers palliation. T2 responds like T1, but
      relapses like T3-4. T2 also implies an intermediate survival. These results have
      implications for staging, informed consent, optimizing radiation treatment, and
      clinical trials.

PMID- 8138437
TI  - Quality of life in patients treated for head and neck cancer: a follow-up study 7
      to 11 years after radiotherapy.
AB  - PURPOSE: To compare health-related quality of life factors in 845 head and neck
      cancer patients randomized to receive either conventional radiotherapy (2 Gy, 5
      days-a-week) or a hypofractionated regimen (2.35 Gy, 4 days-a-week), a follow-up
      study was carried out 7 to 11 years after treatment in the surviving patients,
      representing 30% of the original patient number. METHODS AND MATERIALS: The
      cancer-specific EORTC Core Quality of Life Questionnaire (30 item version; the
      EORTC QLQ-C30) and a 19 item head and neck cancer-specific questionnaire were
      mailed to the 245 surviving patients of the trial. The EORTC QLQ-C30 is comprised
      of six multi-item function scales, three symptom scales, and six single items
      which assess both symptoms and economic consequences of the disease. Two hundred
      and four patients (83%) completed the questionnaire. The two groups of patients
      (N = 103 and N = 101) treated by different fractionating schedules, were
      comparable with regard to sociodemographic variables, tumor site, treatment
      variables (including different types of surgical treatment), and secondary
      primary cancers. Patients in the conventional group had more advanced disease and
      a higher recurrence rate compared to patients in the hypofractionated group.
      RESULTS: Unexpectedly, patients in the hypofractionated group, reported similar
      or better quality of life compared to patients in the conventional fractionated
      group. Patients in both groups described a high level of symptoms, like dryness
      in the mouth and mucus production. Clinical and sociodemographic variables did
      not explain variance in social function, emotional function or fatigue, except
      for the type of surgery performed, which significantly influenced the patients'
      emotional function. CONCLUSION: Long-term survivors of head and neck cancer
      reported a high level of disease and treatment related symptoms. Emotional
      function was significantly influenced by the type of surgical procedure.
      Strategies for future trials in head and neck cancer should continue to attempt
      to stress conservative surgical approaches and coordinated adjuvant therapy to
      maximize local regional control and quality of life. Functional and emotional
      outcome are important parameters which should prospectively be evaluated in
      future clinical trials in head and neck cancer.

PMID- 8138438
TI  - Results of primary and adjuvant CT-based 3-dimensional radiotherapy for malignant
      tumors of the paranasal sinuses.
AB  - PURPOSE: This study reports our clinical experience supporting the normal tissue
      sparing capability of 3-dimensional (3-D) treatment planning when applied to
      advanced neoplasms of the paranasal sinuses. METHODS AND MATERIALS: Between 1986
      and 1992, computed tomography (CT)-based 3-D radiotherapy was used to treat 39
      patients with advanced stage malignant tumors of the paranasal sinuses as all or
      part of initial treatment. Fifteen unresectable patients were treated with
      primary radiotherapy to a median prescribed total dose of 68.4 Gy. Twenty-four
      patients were treated with postoperative adjuvant radiotherapy for close margins
      (< 5 mm), microscopic or gross residual disease. The median prescribed total
      doses were 55.8 Gy, 59.4 Gy and 67.8 Gy, respectively. Globe-sparing fields were
      used in the primary treatment plans of 37 patients (95%). The median follow-up is
      4.5 years (range, 19-86 months). RESULTS: For the unresectable patients who were
      treated with radiotherapy alone, the local control rate at 3 years is 32%. The
      actuarial overall survivals at 3 and 4 years are 32%. For the patients who
      received postoperative adjuvant radiotherapy, none of the five patients
      irradiated for close surgical margins recurred locally. Three of the 14 with
      microscopic residual (21%) recurred locally at 26, 63, and 74 months from the
      start of irradiation. Four of the five with gross residual (80%) recurred locally
      with a median time to recurrence of 2 years. The local control rates at 3 and 5
      years for the adjuvant group are 75% and 65%, respectively. The actuarial overall
      survival at 3 and 5 years are 65% and 60%, respectively. None of the first sites
      of local disease progression were judged to have occurred outside the high-dose
      region. There was one case of mild osteoradionecrosis successfully treated with
      conservative treatment, one case of limited optic neuropathy and one case of
      possible radiation-induced cataract. There was no blindness related to
      irradiation. CONCLUSION: This study indicates that computed tomography-based 3-D
      radiotherapy can preserve critical structures unaffected by tumor invasion and
      achieve the generally expected local control rates when it is used as all or part
      of initial treatment for extensive malignant tumors of the paranasal sinus. The
      presence of gross disease was a major adverse prognostic factor in this study.
      Additional therapeutic maneuvers are essential to improve the local control and
      survival rate in patients with advanced paranasal sinus carcinomas.

PMID- 8138439
TI  - Locally advanced breast cancer: defining an optimum treatment regimen.
AB  - PURPOSE: This retrospective review examines response, local control and freedom
      from distant failure for patients with locally advanced breast cancer treated by
      chemotherapy and radiotherapy without routine surgery. METHODS AND MATERIALS: 67
      patients were treated between January 1980 and December 1988 at Westmead
      Hospital, NSW, Australia. Median follow-up for surviving patients was 56 months.
      Four successive protocols evolved, each with three phases induction chemotherapy
      (adriamycin or novantrone, cyclophosphamide) (three cycles), radiotherapy then
      chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil) of progressively
      shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth
      regimen. RESULTS: Clinical complete response (disappearance of all known disease)
      after chemotherapy, radiotherapy and additional chemotherapy was 18%, 55% and 79%
      respectively. Seven additional patients subsequently underwent mastectomy (N =
      2), local excision (N = 1) or a radiation boost (N = 4) for a total complete
      response rate of 90%. Twenty one patients (31%) failed to achieve a complete
      response (N = 7) or recurred locally (N = 14). The crude 2-year rate of local
      recurrence was 50% for tumors > 10 cm (N = 10) and 14% for smaller tumors (n =
      57) and was not influenced by protocol. Two-year actuarial freedom from distant
      failure was 67% at 2 years. CONCLUSION: Local control can be achieved for
      patients with locally advanced breast cancer with a primary tumor < 10 cm using
      chemotherapy and radiotherapy without routine mastectomy.

PMID- 8138440
TI  - Radiosensitivity of human clonogenic myeloma cells and normal bone marrow
      precursors: effect of different dose rates and fractionation.
AB  - PURPOSE: Evaluation of radiation dose rate and fractionation effects on
      clonogenic myeloma cells. METHODS AND MATERIALS: The radiosensitivity of
      clonogenic myeloma cells was evaluated for seven human myeloma cell lines. The
      lines were maintained in liquid suspension culture. Following radiation, cells
      were plated in semisolid medium using methylcellulose as viscous support.
      Radiation doses up to 12 Gy were delivered at dose rates of 0.05 and 0.5 Gy/min
      by a 60Co source. Each total dose was administered either as a single dose or in
      multiple fractions of 2 Gy. The data were analyzed according to the linear
      quadratic and multi target model of irradiation. RESULTS: Clonogenic progenitors
      of the seven myeloma cell lines differed in their radiosensitivity as measured by
      multiple parameters. The differences were mainly observed at low dose. The most
      effective cytoreduction was seen when radiation was administered in a single
      fraction at high dose rate. The cytoreductive effect on clonogenic myeloma cells
      was compared for clinically practiced total body irradiation (TBI) schedules
      delivered either in a single or in multiple fractions without causing significant
      pulmonary toxicity. The administration of 12 Gy delivered in six fractions of 2
      Gy resulted in a superior reduction of clonogenic cells compared to a single
      fraction of 5 Gy. CONCLUSION: The preparation of bone marrow transplant
      recipients with multiple myeloma using fractionated radiation with a total dose
      of 12 Gy appears to afford better ablation than a single dose of 5 Gy while
      maintaining a low incidence of pulmonary toxicity.

PMID- 8138441
TI  - Effect of nephrotoxic drugs on the development of radiation nephropathy after
      bone marrow transplantation.
AB  - PURPOSE: Chronic renal failure is a significant cause of late morbidity in bone
      marrow transplant patients whose conditioning regimen includes total body
      irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow
      transplant nephropathy), but it may not be the only cause. These studies use a
      rat syngeneic bone marrow transplant model to determine whether nephrotoxic
      agents used in conjunction with bone marrow transplantation (BMT) could be
      enhancing or accelerating the development of radiation nephropathy. METHODS AND
      MATERIALS: Rats received 11-17 Gy TBI in six fractions over 3 days followed by
      syngeneic bone marrow transplant. In conjunction with the bone marrow
      transplants, animals received either no drugs, cyclosporine, amphotericin,
      gentamicin, or busulfan. Drugs were given in schedules analogous to their use in
      clinical bone marrow transplantation. Drug doses were chosen so that the drug
      regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6
      months with periodic renal function tests. RESULTS: Gentamicin had no apparent
      interactions with TBI. Amphotericin increased the incidence of engraftment
      failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused
      late morbidity that appeared to be due to neurological problems, but did not
      enhance radiation nephropathy. Busulfan resulted in a significant enhancement of
      radiation nephropathy. CONCLUSION: Of the nephrotoxins used in conjunction with
      bone marrow transplantation only radiation and busulfan were found to be risk
      factors for bone marrow transplant nephropathy.

PMID- 8138442
TI  - Combining polyamine depletion with radiation therapy for rapidly dividing head
      and neck tumors: strategies for improved locoregional control.
AB  - PURPOSE: Locoregional control is adversely affected as clonogens from rapidly
      proliferating tumors repopulate during a course of radiation therapy. The
      cytostatic agent alpha-difluoromethylornithine (DFMO) was investigated for its
      capacity to slow proliferation kinetics in human squamous cell carcinomas (SCC)
      of the head and neck (H&N), with the ultimate objective of improving locoregional
      control in rapidly dividing tumors treated with radiation therapy. METHODS AND
      MATERIALS: Three human SCC cell lines established from primary H&N tumors were
      evaluated in vitro (cell culture) and in vivo (SCC tumor xenografts in athymic
      mice) for the capacity of DFMO to induce growth inhibition. Flow cytometry
      analysis of SCC tumor growth kinetics and quantitative assessment of polyamine
      biosynthesis inhibition was performed to verify DFMO activity. DFMO effects on in
      vitro SCC radiosensitivity using clonogenic survival were also studied. RESULTS:
      A noncytotoxic exposure to DFMO (5mM x 72 hours) induced pronounced growth
      inhibition in all three SCC cell lines (70-90% at 7 days), and induced a 2-3 fold
      delay in volume doubling time for SCC tumor xenografts when administered orally
      in the drinking water (1.5%) to athymic mice. Kinetic analysis via flow cytometry
      confirmed that DFMO produced a lengthening of SCC cell cycle times, but did not
      alter in vitro radiosensitivity. Inhibition of ornithine decarboxylase (ODC)
      activity and depletion of endogenous polyamines (putrescine and spermidine), were
      confirmed in normal tissue (mouse skin) and in human SCC tumor xenografts of
      athymic mice receiving continuous oral DFMO. CONCLUSION: These data indicate that
      antiproliferative agents, such as DFMO, are capable of altering human SCC growth
      kinetics without altering intrinsic radiosensitivity. Such kinetic modulation may
      therefore provide a strategy to reduce the adverse impact of tumor cell
      proliferation during a radiotherapy treatment course for rapidly dividing tumors
      such as those in the H&N.

PMID- 8138443
TI  - Protection by WR-2721 against radiation plus cis-diamminedichloroplatinum II
      caused injury to colonic epithelium in mice.
AB  - PURPOSE: The study was designed to investigate the ability of S-2-(3
      aminopropylamino) ethylphosphorothioic acid (WR-2721) to protect mouse colon
      mucosa against damage produced by the combined radiation plus cis
      diamminedichloroplatinum II (cis-DDP) treatment. METHODS AND MATERIALS: The
      mucosal damage was quantified by using microcolony assay, which measures the
      survival of epithelial cells in colon crypts. Radiation doses ranged from 8-24 Gy
      gamma rays. Cis-diamminedichloroplatinum at a dose of 13 mg/kg and WR-2721 at a
      dose of 400 mg/kg body weight were given IP before or after irradiation. RESULTS:
      Addition of cis-DDP to radiation within 24 h before and 48 h after irradiation
      reduced the number of crypt cells more than did radiation alone. The highest
      reduction was seen when the drug was given 2 or 6 h before irradiation: the
      damage was increased by a factor of 1.5. Protective effects of WR-2721 were
      tested in the radiation plus cis-DDP combination in which cis-DDP was given 2 h
      before or 2 h after radiation. In the former sequencing, WR-2721 was given 30 min
      before radiation (90 min after cis-DDP); damage was reduced more than the amount
      of damage contributed by cis-DDP (PF = 1.6). When cis-DDP was given 2 h after
      irradiation, WR-2721 was administered 30 min either before irradiation or 30 min
      before cis-DDP. Here, the protective effect was achieved only when WR-2721 was
      given before radiation: the PF was 1.3 in that case and only 1.1 when WR-2721 was
      given before cis-DDP. Thus, WR-2721 must be given before irradiation, but even
      then the degree of protection achieved depends on whether cis-DDP is applied
      before or after irradiation, with the protection being greater in the former
      situation. CONCLUSION: Our observations showed that WR-2721 is a potent protector
      against the injury of mouse colon mucosa produced by the combined radiation plus
      cis-DDP treatment. They have important implications in the clinic, indicating
      that proper timing of WR-2721 administration is crucial for preventing side
      effects of the cis-DDP and radiotherapy combination, where damage to mucosal
      epithelial cells is dose limiting.

PMID- 8138444
TI  - Altered motility causes the early gastrointestinal toxicity of irradiation.
AB  - PURPOSE: Total abdominal radiation produces symptoms of nausea, vomiting
      abdominal cramping and diarrhea. Each of these symptoms is associated with
      disordered intestinal motility. This article reviews studies of large and small
      intestinal contractile activity following radiation exposure. METHODS AND
      MATERIALS: Studies of motility utilize strain gauge transducers surgically
      implanted on the seromuscular layer of the small intestine. All studies were
      performed in mixed breed dogs to record the occurrence of normal contractions,
      giant migrating contractions (GMCs) and retrograde giant contractions (RGCs)
      before, during and after irradiation (22.5 Gy in 9 fractions at 3
      fractions/week). Giant migrating contractions and retrograde giant contractions
      are infrequent in the healthy state. However, in diseased states, GMCs are
      associated with abdominal cramps and diarrhea, and RGCs precede vomiting.
      RESULTS: In fasted animals, fractionated abdominal irradiation dramatically
      increased the frequency of GMCs, with the incidence peaking after the second
      dose. The increased frequency of GMCS occurred as early as a few hours after the
      first radiation fraction, and returned to normal within days of cessation of
      radiation. RGCs were also significantly increased after abdominal irradiation.
      The frequency of RGCs was greatest on the first and sixth dose of radiation.
      Clinically, the dogs developed nausea, vomiting and diarrhea as early as the
      first day of irradiation. In dogs studied in the fed state, decreased amplitude,
      duration, and frequency of postprandial contractions occurred. These changes may
      slow intestinal transit during irradiation. Radiation also produced a striking
      increase in the frequency of colonic GMCs; these changes in colonic motor
      activity were associated with diarrhea as early as the second irradiation.
      CONCLUSION: Changes in GI motility during fractionated irradiation precede the
      appearance of histopathological lesions in the GI tract. Thus, the symptoms of
      nausea, vomiting, and diarrhea experienced during radiotherapy (particularly
      those within the first week) are directly related to changes in bowel motility.
      It is hoped that further understanding of the etiology of these distressing
      symptoms will help to guide their treatment.

PMID- 8138445
TI  - Identification of human in vitro cell lines with greater intrinsic cellular
      radiosensitivity to 62.5 MeV (p-->Be+) neutrons than 4 MeV photons.
AB  - PURPOSE: To identify human in vitro cell lines with a high relative cellular
      sensitivity to fast neutrons as compared to photons and to examine their
      relationship to intrinsic photon radiosensitivity and cellular proliferation
      kinetics. METHODS AND MATERIALS: The clonogenic cell survival following exposure
      to low LET, 4 MeV photons or, high LET, 62.5 MeV (p-->Be+) fast neutrons and the
      cell kinetic parameters of 30 human in vitro cell lines, covering a wide range of
      histologies, were analyzed alone and with previously published data of Fertil and
      Malaise. The relative survival at 1.6 Gy of neutrons (SF1.6) compared to 2 Gy of
      photons (SF2) (the doses per fractions used in the Clatterbridge fast neutron
      studies) and the cell kinetic parameters of the 30 cell lines were also compared.
      The relative lethality of 62.5 MeV fast neutrons was assessed by comparing the
      ratio alpha neutrons/alpha photons to alpha photons or SF1.6 neutrons/SF2 photons
      to SF2 photons. Cellular proliferation kinetics were measured by flow cytometry
      following BrdU incorporation and the relationship of cellular proliferation to
      relative neutron lethality was measured by comparing the alpha neutron/alpha
      photon ratio to the labelling index (LI), potential doubling (Tpot) and ploidy.
      RESULTS: The majority of cell survival curves obtained following exposure to 62.5
      MeV fast neutrons were curvilinear with beta values of similar order to those
      obtained with low LET 4 MeV photons. Comparison of alpha values for neutrons and
      photons revealed a relatively neutron sensitive subset of 9 out of 30 in vitro
      cell lines. This subset was not, however, distinguishable when 1.6 Gy of neutrons
      was compared to 2 Gy of photons. There was no correlation between cell survival
      with neutrons or photons and the cell kinetic parameters Tpot or LI or with DNA
      ploidy. CONCLUSIONS: The use of in vitro assays of neutron and photon
      radiosensitivity irrespective of cell kinetic parameters allows identification of
      neutron sensitive cell populations when the ratio of the alpha values for
      neutrons and photons is compared to the reciprocal of the alpha photon value.
      This relationship is not apparent when fractions of 2 Gy of photons are compared
      to 1.6 Gy of neutrons. Whether or not this identification can be borne out in
      fractionated regimes in the clinic remains to be proved.

PMID- 8138446
TI  - Distribution of the hypoxia marker CCI-103F in canine tumors.
AB  - PURPOSE: The purpose of this study was to identify the prevalence and
      distribution of hypoxic tumor cells in spontaneous canine tumors, and to relate
      these parameters to various tumor and patient characteristics, such as tumor
      volume, tumor type, or tumor location. METHODS AND MATERIALS: Hypoxic tumor cells
      were labeled in vivo in 32 primary malignant canine tumors by bioreductive
      binding of the nitroimidazole hypoxia marker CCI-103F. CCI-103F was given at 40
      mg/kg i.v. Tumors were completely excised, and CCI-103F adducts were detected in
      histologic sections (mean, 138 sections-per-tumor) by peroxidase-antiperoxidase
      immunostaining. Area fraction (area labeled/total area examined) of labeled
      regions was measured via computer assisted image analysis. In tumors with a
      volume < 100 cm3, each cubic centimeter of tumor was examined; in larger tumors
      100 randomly selected 1 cm3 samples were examined. RESULTS: There were 13 soft
      tissue sarcomas, 11 mast-cell tumors, five carcinomas, two lymphosarcomas, and
      one melanoma. Tumors varied from < .001 to > 2000 cm3. Labeled cells were present
      in 31 of 32 canine tumors examined, and varied between 0 and 35%. Mean (+/- SD) %
      label was 12.2% +/- 16.7%; 13 of the 32 dogs had % labeled area < 5.0%. The area
      fraction was not related to tumor site, tumor type, tumor volume, presence and
      degree of necrosis or tumor grade. Dog characteristics such as sex, age, and body
      size did not affect the degree of labeling of tumors. CCI-103F adducts were
      randomly distributed grossly, and at the microscopic level were not found near
      blood vessels or regions containing mitoses. Labeling was seen in a variety of
      normal tissues; not all binding in normal tissues could be attributed to hypoxia.
      CONCLUSION: CCI-103F labeling of hypoxic regions in tumors provides a
      nonradioactive method of detecting nitroimidazole adducts at the cellular level,
      and allows concurrent histologic examination. The pattern of labeling is
      consistent with detection of hypoxic tumor cells arising from oxygen diffusion
      limitations. This method may have clinical applicability in the detection of
      tumor hypoxia.

PMID- 8138447
TI  - Human tumor extracellular pH as a function of blood glucose concentration.
AB  - PURPOSE: Mammalian cells are sensitized to hyperthermia when the extracellular pH
      (pHe) is acutely reduced to < pH 7.0-7.2. However, cells chronically adapted to
      low pHe may not demonstrate such sensitivity. Although much of the extracellular
      environment of human tumors is at lower than normal physiological pH, it may be
      necessary to acutely acidify tumors to cause a change in the therapeutic response
      to hyperthermia. The purpose of this study was to reduce extracellular pH in
      human tumors by elevation of blood glucose. METHODS AND MATERIALS: The change in
      tumor pHe was measured as a function of the change in blood glucose concentration
      after oral administration of 100 g glucose in 25 fasting, nondiabetic patients.
      pHe was determined by needle microelectrodes, and blood glucose determined by
      "Chemstrips" and a glucometer. In some patients blood glucose concentration rose
      with time after ingestion to a peak change of 50-100 mg/dL between 30-70 min and
      then began to decrease. In another group of patients glucose concentration
      increased by 100-200 mg/dL over 30-90 min and remained elevated as if the
      patients in this group were Type II diabetics. RESULTS: In 14 transient
      hyperglycemic patients (56%), as blood glucose increased tumor pHe decreased by a
      mean of -0.17 +/- 0.04 pH units (p < or = 0.0001, range of -0.41-(+)0.07). By
      contrast in eight persistent hyperglycemic patients, tumor pHe remained unchanged
      or actually increased an average of 0.03 +/- 0.04 pH units (range of -0.15-(
      )0.14). Normal tissue pHe in five patients was unchanged by hyperglycemia, pHe =
      7.33 +/- 0.03. Among all patients, 52% exhibited a pHe decrease > or = 0.1 pH
      unit, and 24% exhibited a pHe decrease > or = 0.2 pH unit. In five transient
      hyperglycemic patients whose preglucose tumor pHe was between 6.90 and 7.22, the
      average decrease in pHe induced by hyperglycemia was 0.25 +/- 0.05 pH unit. A
      linear relationship was observed between the change of pHe and the maximum change
      in blood glucose such that the greatest decrease in tumor pHe occurred when the
      glucose change was minimal. The slope was 0.0017 +/- 0.0005 pH units/mg/dL
      glucose (p < or = 0.005). The linear relationship included both tumors in
      transient hyperglycemic patients and in persistent hyperglycemia patients.
      CONCLUSION: Since patients who exhibited the lowest change in blood glucose
      exhibited the greatest decrease in tumor pHe, it may be that cells in these
      patients were better able to transport glucose intracellularly which in tumor
      cells would permit a more rapid production of lactic acid from aerobic and/or
      anaerobic glycolysis. These data may be helpful in predicting the response of
      individual patients to oral hyperglycemia as a clinical thermosensitizer.

PMID- 8138448
TI  - The impact of radiation dose in combined external beam and intraluminal Ir-192
      brachytherapy for bile duct cancer.
AB  - PURPOSE: To examine the impact of radiation dose on both survival and morbidity
      in combined modality treatment of bile duct cancer. METHODS AND MATERIALS: Forty
      eight patients with cancer of the extrahepatic bile ducts were treated at Thomas
      Jefferson University Hospital from 1984-1990. Twenty-four patients received
      radiation as part of a combined modality approach using external beam radiation,
      brachytherapy implant and chemotherapy. Twenty-four patients received no
      radiation in the course of their treatment. Radiation was delivered via high
      energy photons at standard fractionation, 5 days/week, for an average of 46 Gy.
      The implant used Ir-192 ribbon sources (average activity was 29 mCi, active
      length was 6 cm) for a mean dose of 25 Gy at 1 cm. Chemotherapy consisted of 5-FU
      alone or combined with adriamycin or mitomycin-C. RESULTS: Two-year survival for
      all 48 patients was 18% (median 9 months). Patients treated with radiation had a
      2-year survival of 30% (median 12 months) vs. the no-radiation group, 17% (5.5
      months, median), p = 0.01. Those treated to > 55 Gy experienced an extended 2
      year survival of 48% (24 months, median), vs. those receiving < 55 Gy, 0% (6
      months, median), p = 0.0003. This benefit was also seen when patients were
      stratified by T-stage. A dose response is further suggested by a lengthening of
      the median survival with increasing radiation dose (4.5 months, 9 months, 18
      months and 25 months for < 45 Gy, 45-55, 55-65, 66-70 Gy, respectively). Neither
      surgical resection nor chemotherapy produced statistically significant benefits
      as independent variables. Complications due to radiation occurred in only one
      patient. CONCLUSION: A dose response is shown with more than double the 2-year
      and median survival for doses > 55 Gy. A brachytherapy dose of 25 Gy, plus 44-46
      Gy external beam is well tolerated. High dose combined brachytherapy and external
      beam radiation (60-75 Gy) appears to be the most effective modality for
      extrahepatic bile duct cancer.

PMID- 8138449
TI  - Dosimetric characteristics, air-kerma strength calibration and verification of
      Monte Carlo simulation for a new Ytterbium-169 brachytherapy source.
AB  - PURPOSE: Ytterbium-169 (169Yb) is a promising new isotope for brachytherapy with
      a half life of 32 days and an average photon energy of 93 KeV. It has an Ir-192
      equivalent dose distribution in water but a much smaller half-value layer in lead
      (0.2 mm), affording improved radiation protection and customized shielding of
      dose-limiting anatomic structures. The goals of this study are to: (a)
      experimentally validate Monte Carlo photon transport dose-rate calculations for
      this energy range, (b) to develop a secondary air-kerma strength standard for
      169Yb, and (c) to present essential treatment planning data including the
      transverse-axis dose-rate distribution and dose correction factors for a number
      of local shielding materials. METHODS AND MATERIALS: Several interstitial 169Yb
      sources (type 6) and an experimental high dose-rate source were made available
      for this study. Monte-Carlo photon-transport (MCPT) simulations, based upon
      validated geometric models of source structure, were used to calculate dose rates
      in water. To verify MCPT predictions, the transverse-axis dose distribution in
      homogeneous water medium was measured using a silicon-diode detector. For use in
      designing shielded applicators, heterogeneity correction factors (HCF) arising
      from small cylindrical heterogeneities of lead, aluminum, titanium, steel and air
      were measured in a water medium. Finally, to provide a sound experimental basis
      for comparing experimental and theoretical dose-rate distributions, the air-kerma
      strength of the sources was measured using a calibrated ion chamber. To eliminate
      the influence of measurement artifacts on the comparison of theory and
      measurement, simulated detector readings were compared directly to measured diode
      readings. The final data are presented in the format endorsed by the Interstitial
      Collaborative Working Group. RESULTS: The in-air calibration revealed that the
      air-kerma strength per unit activity (mCi), as quoted by the vendor, varied from
      1.30 to 1.57 cGy.cm2/mCi.h depending on seed design. The maximum difference
      between measured and MCPT-simulated absolute diode readings on the transverse
      axis was less than 2%, indicating that MCPT accurately predicts dose rate in
      medium for brachytherapy sources in this energy range. Comparison of measured and
      simulated HCFs for each of the 16 different cylindrical heterogeneities
      demonstrated 1-3% agreement. The HCFs vary by as much as 200% with respect to
      distance and by as much as 48% as a function of disk diameter, showing that HCF
      is strongly dependent on heterogeneity location and lateral dimensions as well as
      thickness. The dose-rate constant for water medium was found to be 1.225 cGy/h
      per kerma unit air-strength and 1.962 cGy/h per unit mCi as measured by the
      vendor. CONCLUSION: Monte Carlo simulation is an accurate and powerful tool for
      dosimetric characterization of brachytherapy sources in this energy range. Thin
      lead foils produce shielding factors comparable to standard shielded applicators
      for 137Cs. Meaningful theoretical absolute dose calculations in brachytherapy
      require accurately implemented air-kerma strength standards.

PMID- 8138450
TI  - Quantifying the effect of dose inhomogeneity in brachytherapy: application to
      permanent prostatic implant with 125I seeds.
AB  - PURPOSE: To quantitate the influence of dose inhomogeneity on brachytherapy
      efficacy. METHODS AND MATERIALS: A computed tomography-based system of planning,
      implementation and evaluation was used to generate tumor-specific dose-volume
      histograms of eight permanent 125I implants of prostate cancers. The
      radiobiological effect was then assessed, voxel by voxel, in terms of the
      biologically effective dose and the associated cell inactivation. The overall
      cell survival of the entire target volume was then computed. To evaluate the
      influence of inhomogeneity, the dose-volume histogram was modified in an
      iterative fashion, with the corresponding surviving fraction calculated after
      each step. Specifically, the volume in the highest dose bin was combined with
      that in the next bin to give a new frequency distribution from which cell
      survival was generated. Tumor control probability (TCP) was also used as an
      endpoint, using the same iterative procedure. RESULTS: Doses 20-30% higher than
      D99 (the dose that covered 99% of the target volume) contributed to additional
      cell inactivation, but still higher doses did not further increase cell kill.
      With homogeneous irradiation at D99 as a reference, we defined the inhomogeneity
      enhancement factor as the ratio of the biologic effective dose of the actual
      implant to that of the reference dose distribution. The calculated enhancement
      factors were inversely dependent on tumor potential doubling time (Tp), about 1.2
      1.3 for a Tp of 30 days, and between 1.3 and 1.7 if Tp = 10 days, with higher
      values for implants with low D99. Dose inhomogeneity enhanced TCP. For implants
      with high control probabilities does significantly higher (> 20%) than the D99
      value did not further enhance the tumor control probabilities. In contrast, for
      implants with relatively low tumor control and D99 values, the control
      probability continued to increase with doses significantly higher than D99, up to
      a dose of 2 x D99. The underlying reasons were the incorporation of patient
      "population averaging" in the calculation and the saturation of tumor control
      dose response at about 120 Gy. CONCLUSION: Dose heterogeneity in implants
      increased tumor cell kill and local control probability, although doses > 20%
      higher than the prescription dose is wasted. The increase the beneficial effect
      of dose inhomogeneity may be greatest when most needed.

PMID- 8138451
TI  - Validity of universal wedge equation over the range of 60Cobalt to 25 MV photon
      beam energies.
AB  - PURPOSE: Evaluating the validity of the universal wedge equation over the range
      of 60Cobalt (60CO) to 25 MV photon beam energies. METHODS AND MATERIALS: The
      universal wedge equation relates the beam weight of the wedged field to the
      effective wedge angle produced by combining the wedged field to the nonwedged
      field and is expressed as tan (theta) = B tan (theta w), where B is the
      normalized weight imposed on the wedged field, theta w is the maximum wedge angle
      of the wedge filter, and theta is the effective wedge angle. The isodose
      distributions from 60Co to 25 MV photon beam energies were used. For each photon
      energy, the isodose distributions of wedged and nonwedged fields were combined in
      different proportions. The effective wedge angle was determined from each
      resultant isodose distribution. RESULTS: The relationship between the weight of
      wedged field and the effective wedge angle was found to be nonlinear for wedge
      filters with maximum wedge angle greater than 30 degrees. The universal wedge
      equation predicts the effective wedge angle to within 2 degrees compared to the
      measured value.

PMID- 8138452
TI  - Treatment-related symptoms during the first year following transperineal 125I
      prostate implantation.
AB  - PURPOSE: To summarize the urinary, rectal, and sexual symptoms occurring during
      the first 12 months following 125I prostatic implantation. METHODS AND MATERIALS:
      Thirty-one patients with Stage T1 or T2 prostatic carcinoma were evaluated for
      morbidity following computed tomography-guided transperineal 125I implants from
      1988 to 1991. The median total activity used was 47 mCi (range 35-73 mCi).
      Toxicity was evaluated using a modification of the Radiation Therapy Oncology
      Group grading system. RESULTS: Nocturia was the most common treatment-related
      symptom, reported by 80% of patients within 2 months after implantation, and
      persisted at 12 months in 45% of the patients. Mild dysuria developed in 48% of
      patients within 2 months of implantation; two patients needed analgesics for
      their dysuria. Terazosin hydrochloride (2-10 mg qd) provided subjective
      improvement of urinary symptoms in seven of eight patients in whom it was tried.
      Rectal urgency, soft stools, and increased frequency of bowel movements was
      reported by 25% of the patients within 1-2 months after implantation. The
      incidence of asymptomatic rectal bleeding or ulceration occurring at any time
      after implantation was 47%, but resolved in all patients with expectant
      treatment. Self-limited ulceration of the rectal mucosal occurred in 16%, but
      only one patient developed a prostato-rectal fistula, managed with an ileal
      conduit. Five of the 18 potent patients experienced discomfort on erection or
      ejaculation, beginning within several weeks of their implant. The discomfort
      resolved within 6 months in three of the patients, but persisted for 18 and 24
      months in the other two. CONCLUSION: 125I implantation, as performed in this
      series, is generally associated with only mild-moderate genitourinary and rectal
      symptoms that may persist 6 months or more after implantation. Prostatic
      carcinoma, Brachytherapy, Morbidity.

PMID- 8138453
TI  - Carcinoma of the nasopharynx in young patients.
AB  - PURPOSE: To provide an analysis of eighteen cases of adolescent nasopharyngeal
      carcinoma treated between 1971 and 1989. METHODS AND MATERIALS: Between 1971 and
      1989, 48 cases of nasopharyngeal carcinoma were evaluated at the Medical College
      of Georgia Hospital and Clinics. Eighteen patients between the ages of 9 and 29
      years were treated at the Georgia Radiation Therapy Center. All patients
      presented for treatment with (AJCC) Stage IV disease. Fifteen patients with
      lymphoepithelioma and three with squamous cell carcinoma histologies received
      definitive radiation therapy to a median dose of 64.8 Gy. Males outnumbered
      females by more than 2:1 and the majority of patients (67%) were black. Nine
      patients received multiagent adjuvant chemotherapy. RESULTS: Thirteen patients
      are alive from 7 to 166 months (median 32 months) including three with disease at
      17, 24, and 132 months. Overall and disease-free survival at 5 and 10 years were
      63% and 54%, respectively. Five patients died from disease; four patients had
      pulmonary metastases while one had CNS metastasis. Eighty percent of relapses
      occurred within the first 2 years following treatment. Acute and chronic
      toxicities were limited, consisting primarily of mucositis and xerostomia.
      Radiation doses of 65 Gy or more (p = 0.049) and age greater than 20 years (p =
      0.005) were positive prognosticators for survival. Adjuvant chemotherapy, race,
      and sex were not found to be of prognostic value. Disparities in the distribution
      of patients with lymphoepithelioma and squamous cell histologies and the
      presentation of advanced regional disease precluded analysis for prognostic
      significance of histology and nodal status in this series. CONCLUSION: The
      results of the present series compare favorably with those published from other
      institutions. High doses of radiation and a high systemic failure rate continue
      to be the fundamental obstacles to effective management and enhanced survival for
      patients with nasopharyngeal carcinoma.

PMID- 8138455
TI  - Affect: a biological basis of art.

PMID- 8138454
TI  - The empathic mode of perception: an update.

PMID- 8138456
TI  - The empathic imagination: empathy and inscapes.

PMID- 8138457
TI  - Palimpsest or tabula rasa: developmental biology of the brain.

PMID- 8138458
TI  - Who needs their dreams? The usefulness of dreams in psychotherapy.

PMID- 8138459
TI  - Schizophrenia, the pervasive psychosis: paradoxes and empathy.

PMID- 8138460
TI  - Mother-infant semiotics: intuition and the development of human subjectivity-
      Klein/Lacan: fantasy and meaning.

PMID- 8138461
TI  - Dissociation, development, and the psychobiology of trauma.

PMID- 8138462
TI  - Empathy, psychoanalytic practice in the 1920s, and Ferenczi's Clinical diary.

PMID- 8138463
TI  - Ferenczi's Clinical diary: roadmap to the realm of primary relatedness.

PMID- 8138464
TI  - Countertransference, Ferenczi, and Washington, DC.

PMID- 8138465
TI  - I can see: the transformative process of feminist awareness.

PMID- 8138466
TI  - Women's anger and its meanings: a phenomenological perspective.
AB  - This study focused on the interactions of somatizations, thoughts, and social
      processes evolving from unrecognized, unexpressed, or repressed anger in women.
      Material from patients' clinical narratives was phenomenologically described and
      interpreted. The most critical finding was the transformation of anger as lived
      by women into socially acceptable pathology. Anger was left in silence, and the
      possibilities for its expression were found in physiological disorders, substance
      abuse, self-deprecation, and affiliation problems, among other conditions.

PMID- 8138467
TI  - The pioneers of rural Pakistan: the Lady Health Visitors.
AB  - Since 1978, when the World Health Organization and the United Nations
      International Children's Emergency Fund called for urgent action by all
      governments to provide appropriate health care for the underprivileged, the world
      community has attempted to implement primary health care strategies. Pakistan,
      with a population of 118 million people, is one of those countries where the
      rural population and the underprivileged groups in the katchi-abadis (squatter
      settlements) of the urban areas lack appropriate and accessible health services.
      This article highlights the community experiences of a remarkable group of young
      Muslim women, the Lady Health Visitors (LHVs) of the Aga Khan Health Services,
      who deliver primary health care services to disadvantaged women and children in
      the northern mountainous areas and rural villages of Pakistan. The LHVs are the
      first contact with the health care system that these underprivileged women
      experience. The LHVs cure, care, teach, and train traditional birth attendants.
      In addition, they perform health promotion and document their findings. To
      provide their maternal and child health services, the LHVs travel by foot through
      miles of rough terrain to settlements and villages. Prenatal and postnatal care,
      anemia, diarrhea, and malnutrition are among the major health care problems of
      these rural women and their children under 5 years of age.

PMID- 8138468
TI  - Social support and relationship change after childbirth: an expectancy model.
AB  - Much has been written about social support, but little is known about the
      processes that promote continuity or discontinuity in supportive relationships. A
      proposed model of relationship processes (Levitt, 1991) specifies that changes in
      the quality of close relationships are likely to occur when expectations for
      social support are tested and disconfirmed. Relationships are particularly
      vulnerable to change after major life events, such as childbirth, when increased
      support needs precipitate the testing of expectations. In a preliminary
      assessment of this model, 43 mothers were interviewed at 1 month and 13 months
      after birth. Changes in relationship satisfaction were related strongly to the
      extent to which mothers perceived that their expectations for support had been
      disconfirmed. The results are consistent with the proposed model and suggest the
      value of considering the effects of social support in light of the individual's
      expectancies.

PMID- 8138469
TI  - Grieving the wanted child: ramifications of abortion after prenatal diagnosis of
      abnormality.
AB  - Prenatal diagnosis is increasingly common. Whereas amniocentesis is typically
      performed in the second trimester, chorionic villus sampling (CVS) is a first
      trimester procedure, which makes an earlier, safer abortion possible. However,
      CVS carries a slightly higher risk of miscarriage and other complications. In
      choosing a procedure, couples (with the aid of genetic counseling) must weigh the
      risks of miscarriage against the odds and implications of an abnormal diagnosis.
      Interviews with women who decided on abortions after amniocentesis or CVS and
      meetings with genetic counselors indicate that both types of abortion are more
      traumatic than is commonly realized. Both dash dreams and hopes. Termination
      after amniocentesis also forces the mother to take an active part in the life and
      death of a nearly viable fetus. Yet, because abortions for fetal abnormality are
      statistically rare, there is little societal understanding and minimal support
      for those who experience them. This is true of health care workers as well as for
      the couple's primary support group.

PMID- 8138470
TI  - Stresses and rewards experienced by employed mothers.
AB  - As an increasing percentage of mothers of preschool children enter the labor
      force, there is a need for a better understanding of the experience of employment
      and its impact on women and their families. In the present study, employed women
      enacting multiple roles were asked to describe their perceptions of the stresses
      and rewards of the experience. One hundred eighteen employed mothers of preschool
      children were interviewed. The major stresses that emerged from the responses
      included lack of time, child-related problems, and maternal guilt. Rewarding
      aspects included personal benefits, financial rewards, and improved family life.
      Implications for families, health practitioners, and researchers are discussed.

PMID- 8138471
TI  - What family planning methods women use and why they change them.
AB  - Each woman in a sample of 800 women from a nonprofit, private family planning
      clinic reported using at least one contraceptive method at some time in her life.
      Over the 15-year period that the sample represented, women made from 1 to 26
      family planning visits. The women reported using as many as eight different
      methods and making up to 11 changes in method. The reasons for changing methods
      were, for the most part, logically related to the method, at least as far as
      common user complaints and side effects were concerned, but they also reflected
      misperceptions regarding relative risk of methods and a low tolerance for a
      method's disadvantages. A lack of congruence between choice and use was revealed,
      as women returned for care and reported that they had not used the contraceptive
      method they had chosen at the last family planning visit or had changed methods
      one or more times since that visit.

PMID- 8138472
TI  - Managing incontinence: women's normalizing strategies.
AB  - Women's strategies for managing urinary incontinence were examined in a grounded
      theory study. The women's basic social concern was dealing with incontinence in a
      manner that enabled them to feel normal. Feeling normal meant being able to do
      what they wanted to do and needed to do to have a normal life-style as they
      perceived it. This goal was accomplished by normalizing incontinence and its
      management. Normalization was achieved by directing its course through self
      management, accounting for it in terms of personal history and life experiences,
      and delaying medical counsel. These strategies are described. The findings
      provide fresh insights about women's response to incontinence and their practice
      of self-managing its consequences.

PMID- 8138473
TI  - Sexual networking of market women in Benin City, Edo State, Nigeria.
AB  - The manifestation of acquired immune deficiency syndrome (AIDS) all over the
      world has increased the need for information on the nature and pattern of sexual
      networking in Africa, where there is a dearth of such information. In the present
      study, information on the sexual networking of market women in Benin City,
      Nigeria, was obtained using a questionnaire instrument. The questionnaire covered
      the sexual, reproductive, and health behaviors of these women. The data revealed
      that the levels of both premarital and extramarital sexual networking are high.
      Such a high degree of sexual networking has exposed a number of these women to
      sexually transmitted diseases. The manifestation of AIDS in this society will be
      widespread and devastating to the people and the society because these women are
      in a polygamous relationship in a society that frowns on the use of
      contraceptives by couples. In addition, controversies surround the correlation
      between socioeconomic status (SES) and AIDS, geographical areas of prevalence,
      and the role of prostitutes in the spread of the disease. For example, studies in
      Africa show that whereas there is no correlation between SES and AIDS in
      Kinshasa, the attack rate was higher in educated people in Rwanda and Zambia.
      Moreover, there are predominantly urban outbreaks in other countries, such as
      Uganda (Piot & Carael, 1988).

PMID- 8138474
TI  - Elmer Seth Savage, 1884-1943: a brief biography.

PMID- 8138475
TI  - The effect of flavor concentration and toxin dose on the formation and
      generalization of flavor aversions in lambs.
AB  - If an animal experiences gastrointestinal malaise after eating a novel feed, it
      develops a dislike for the feed called a conditioned flavor aversion (CFA).
      Understanding flavor aversions is important for diet-training procedures,
      understanding animal responses to poisonous plants, and preparing animals for new
      foraging environments. Our research objectives were to determine how variation in
      1) flavor concentration (oregano) and 2) dose of gastrointestinal toxin (lithium
      chloride; LiCl) affected the establishment of CFA in lambs. In a series of
      experiments feeding lambs ground grains mixed with oregano, we examined how the
      formation of a CFA to one ground grain, with or without oregano, influenced the
      consumption of another oregano-flavored grain. We determined that 1) the higher
      the toxin dose, the stronger the CFA, the greater the generalization of the CFA
      to a similar feed, and the greater the avoidance of a novel feed; 2) lambs
      generalized aversions from familiar to novel feeds when both feeds had a flavor
      in common; and 3) the concentration or intensity of feed flavor apparently did
      not affect the acquisition or generalization of a CFA, but it did influence the
      acceptance of a novel feed. Our findings suggest that flavor aversions may be
      important in the acceptance of harvested or processed feeds.

PMID- 8138476
TI  - Phosphorus-31 nuclear magnetic resonance study of energy metabolism in intact
      slow- and fast-twitch muscles of rats.
AB  - The time course of the catabolism of phosphorylated metabolites was studied by
      phosphorus-31 NMR(31P NMR) spectroscopy over a 6-h period after the isolation of
      rat slow- and fast-twitch muscles, the soleus and the extensor digitorum longus
      (EDL), respectively, obtained without any muscle damage. In both muscles, rapid
      depletion of creatine phosphate was followed by a decrease in ATP. These high
      energy phosphates disappeared earlier in the soleus than in the EDL. In both
      muscles, inorganic phosphate (Pi) largely increased in a biphasic pattern, and
      sugar phosphates (SP) also showed considerable increase. The NMR-visible total
      phosphates (NTP) increased significantly in the soleus during the latter stage of
      observation. This increase in NTP was attributed to an increase in Pi. Although
      the two muscles showed the same initial (7.21) and final (approximately 5.9)
      intracellular pH (pHi), the pattern of pHi decline differed between these
      muscles. The rapid fall of pHi in the soleus in the early stage suggests that
      nonlactic acid acidosis plays a significant role in postmortem changes.

PMID- 8138477
TI  - Predicting intramuscular fat in beef longissimus muscle from speed of sound.
AB  - The ultrasonic A-mode method was investigated for intramuscular fat measurement
      of beef. Cubes of meat samples that had different marbling scores were used as
      specimens. Ultrasonic speed decreased with increasing fat concentration. The
      correlation coefficient was -.82 (P < .05). Conversely, the correlation
      coefficient between visual marbling score and fat concentration was .70 (P <
      .05). Quantitatively, from the first derivative of a nonlinear function, it was
      concluded that the speed decreased at a rate of 2.69 m/(s-% fat) as a function of
      intramuscular fat. A nonlinear regression model to predict intramuscular fat
      content in beef was developed as follows: percentage of fat concentration =
      7132.1574-9.1222 x (speed) + 2.91803 x 10(-3) x (speed)2 (R2 = .81). The
      nonlinear model was capable of predicting intramuscular fat concentration with
      90% accuracy (> 8% fat) and 76.4% accuracy (< 8% fat), respectively (P < .001).

PMID- 8138478
TI  - Measuring intramuscular fat in beef with ultrasonic frequency analysis.
AB  - Frequency analysis of Fourier spectra from ultrasonic signals was used for
      predicting intramuscular fat content of beef tissue. The most significant
      parameter in the frequency domain for predicting intramuscular fat concentration
      in beef was the number of local maxima. It represents the discontinuity of the
      Fourier spectrum caused by inhomogeneous fat concentrations in the longissimus
      muscle, which had the correlation coefficient .89 (P < .05) when a 2.25-MHz shear
      probe was used. The optimum frequency for predicting the amount of intramuscular
      fat content in the longissimus muscle was found to be 1.92 MHz. A multivariate
      regression model was developed using parameters in the frequency domain as
      follows: percentage of fat concentration = 1.790 - 2.373x (lower frequency) +
      .049x (bandwidth) + 1.178x (local maxima) (R2 = .82). Validation demonstrated
      that the multivariate model in the frequency domain was capable of predicting
      intramuscular fat concentration with an average of 1.17 percentage of fat error
      (P < .05). The multivariate model was most appropriate for predicting
      intramuscular fat below 4%. The mean accuracy of the model in the frequency
      domain was approximately 79%.

PMID- 8138479
TI  - Apparent digestibility and retention of nutrients bound to phytate complexes as
      influenced by microbial phytase and feeding regimen in pigs.
AB  - Five barrows of approximately 45 kg BW, fitted with post-valvular T-cecum
      cannulas at the ileo-cecal junction, were assigned randomly to five treatments (5
      x 5 Latin square design) to assess the effect of microbial phytase and feeding
      regimen (frequency and level) on the apparent digestibilities (total tract [ATTD]
      and ileal [AID]) and retention of nutrients. A corn-tapioca-soybean meal diet of
      low intrinsic phytase activity, containing no added inorganic P, was fed either
      without or with microbial phytase from Aspergillus niger var. Van Tieghem (800
      phytase units/kg of diet) at different feeding frequencies (once, twice, or seven
      times per day) and feeding levels (2.3 vs 2.8 times the maintenance requirement
      for ME, i.e., 418 kJ ME/BW.75). Microbial phytase enhanced significantly the ATTD
      of DM, OM, CP, Ca, total P, and amino acids (except for cystine and proline).
      Also, the AID of total P, phytic acid, methionine, and arginine was increased (P
      < .05 or .01). As a consequence of adding this enzyme, the retention (grams/day)
      of N, Ca, and P was greater (P < .01) and their daily excretion was diminished by
      5.5, 2.2, and 1.9 g/d, respectively. The feeding level exerted a minor effect on
      the ATTD and AID (except for methionine and cystine), although the retention
      (grams/day) of N, Ca, and P was greater (P < .01) at the higher level of feeding.
      The feeding frequency influenced significantly the ATTD of Ca, tryptophan, and
      isoleucine and the AID of phytic acid, cystine, arginine, isoleucine, and
      phenylalanine. Also, N retention (grams/day) was reduced in pigs fed once daily
      (P < .01).

PMID- 8138480
TI  - Energy value of medium-chain triglycerides and their efficacy in improving
      survival of neonatal pigs.
AB  - Two experiments were conducted to determine the energy value of medium-chain
      triglycerides (MCT) and to assess whether oral doses of MCT could improve the
      survival of neonatal pigs. Twenty 6-d-old pigs from seven litters were fed a milk
      replacer containing 0, 5, 10, or 20% MCT. Feces and urine were collected for 10 d
      to determine the energy value of MCT. The determined GE, DE, ME, and N-corrected
      ME of MCT were 8,279, 8,693, 7,867, and 7,781 kcal/kg, respectively. Two hundred
      forty-eight neonatal pigs from 23 litters were orally dosed with 6 mL/kg.75 of
      either MCT or saline twice (14 and 26 h of age), and the growth and mortality of
      pigs at 1, 2, 3, 7, 14, and 28 d of age were observed. The growth of pigs from
      birth to 28 d of age was not affected (P > .05) by MCT. Medium-chain
      triglycerides increased (P < .05) the mortality of large (> 1.5 kg) pigs during 0
      to 7 and 0 to 28 d of age and did not reduce (P > .05) the mortality of small (<
      1 kg) or medium (1 to 1.5 kg) pigs. In summary, MCT was effective as an energy
      source for pigs, but neonatal pigs dosed with MCT did not have improved growth or
      survival from birth to weaning.

PMID- 8138481
TI  - Calcium level affects the efficacy of supplemental microbial phytase in corn
      soybean meal diets of weanling pigs.
AB  - A 2 x 2 x 2 factorial experiment was conducted with 64 pigs (4 wk old, 8.04 +/-
      .50 kg BW) to determine the effect of various dietary concentrations of Ca,
      vitamin D, and microbial phytase (Aspergillus niger) on phytate-P utilization. A
      low-P, corn-soybean meal diet was supplemented with two levels of phytase
      (unit/gram), 750 (suboptimal) and 1,200 (optimal); of vitamin D (international
      unit/kilogram), 660 (normal) and 6,660 (high); and of Ca (percentage), .4 (low)
      and .8 (normal). Pen feed consumption and individual pig weights, plasma
      inorganic P and Ca concentrations, and plasma alkaline phosphatase (AP) activity
      were measured at d 10, 20, and 30. The normal dietary Ca concentration had an
      adverse effect (P < .05) on all the response measures. The depressive effect of
      the normal dietary Ca on performance was greater (P < .05) at the normal vitamin
      D level or at the optimal phytase level than at the other levels of these two
      factors. The elevation in plasma AP activity in pigs fed the normal dietary Ca
      was greater (P < .05) at the suboptimal than at the optimal phytase level. The
      decreases in plasma inorganic P concentration and increases in plasma Ca
      concentration associated with the normal dietary Ca were substantial. In
      conclusion, the normal level of Ca in the diet greatly reduced the efficacy of
      supplemental phytase. Raising vitamin D in the diet partially offset this adverse
      effect but did not produce further improvement when the Ca level was low.

PMID- 8138482
TI  - The effects of immunization against luteinizing hormone-releasing hormone on
      performance, sexual development, and levels of boar taint-related compounds in
      intact male pigs.
AB  - The effect of a newly developed anti-LH-RH vaccine on the performance, sexual
      development, and incidence of boar taint-related compounds was investigated in
      young intact male pigs. At 29 kg BW, 40 crossbred intact males and 20 castrates
      were allocated to three groups. Castrates and half of the intact males were
      untreated. The remaining intact males were immunized against LH-RH at 29 kg and
      again at 89 kg BW. All pigs were slaughtered at 105 kg BW. Compared with control
      intact males, feed efficiency in castrates was decreased by 10%, muscle content
      was reduced by 5%, and carcass fat content was increased by 26%. Growth
      performance and carcass traits did not differ significantly between immunized and
      control intact males. Genital tract weight, measured at slaughter, was decreased
      (P < or = .002) by immunization. Plasma testosterone concentrations were not
      significantly affected at 89 kg BW, whereas they were sevenfold lower (P < .001)
      in immunized than in control intact males at 105 kg BW. Fat androsterone levels,
      measured at slaughter, were substantially reduced (P < .001) from .66 +/- .07
      microgram/g in control to .21 +/- .01 microgram/g in immunized intact males.
      Rates of testicular steroid biosynthesis, measured in vitro, were decreased by
      immunocastration. Fat skatole levels were very low and did not differ
      significantly between the three groups. The present results demonstrate that anti
      LHRH immunization was effective in reducing the level of androstenone, a boar
      taint-related compound, although having a limited effect on the performance of
      the animals.

PMID- 8138483
TI  - Digestible threonine requirements of starter and finisher pigs.
AB  - The digestible threonine (Thr) requirements of starter (28 d of age initially, 6
      to 16 kg) and finisher (58 to 96 kg) pigs were determined. Each growth trial
      evaluated control and basal diets and the basal diet plus four incremental
      additions of L-Thr (.60 to .76% dietary Thr for starter pigs and .30 to .50%
      dietary Thr for finisher pigs). The basal diet fed to starter pigs contained
      17.6% CP and 1.25% lysine and was based on sorghum, peanut meal, soybean meal,
      and dried whey. The basal diet fed to finisher pigs contained 9.7% CP and .75%
      lysine and was based on sorghum supplemented with lysine, methionine, tryptophan,
      and isoleucine. Incremental increases in dietary Thr increased (P < .05) ADG and
      ADFI of starter pigs quadratically. Gain/feed increased (P < .01) linearly. Based
      on broken-line regression analyses, .63% Thr maximized ADG of starter pigs. Daily
      gain and gain/feed of finisher pigs increased linearly (P < .01) and
      quadratically (P < .01) as dietary Thr content increased. Broken-line regression
      analyses determined that .41% Thr maximized ADG and gain/feed. Digestion trials
      with pigs fitted with an ileal T-cannula determined that the basal starter and
      finisher diets contained .43 and .17% apparent ileal digestible Thr and 3.35 and
      3.38 Kcal of fecal DE/g, respectively. On average, crystalline Thr had an
      apparent ileal digestibility of 98%. Based on these values and the total Thr
      requirements given above, the digestible Thr requirement of finisher pigs for
      maximum ADG and gain/feed was estimated to be .28%.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138484
TI  - Effects of replacing milk and soybean products with wheat glutens on
      digestibility of nutrients and growth performance in nursery pigs.
AB  - Three experiments were conducted to determine the nutritional value of wheat
      gluten (WG) for weanling pigs. In Exp. 1, 72 pigs (4.2 kg average BW) were used
      in a N metabolism experiment. Treatments were 1) casein-corn-based control; 2, 3,
      4, 5, and 6) Diet 1 with flash-dried WG, spray-dried WG, two enzyme-modified (to
      increase solubility) WG, and soybean meal (SBM) used to replace casein,
      respectively. The diet with casein had the greatest apparent N digestibility and
      apparent biological value (P < .002), and diets with WG had greater apparent N
      digestibility than the diet with SBM (P < .01). In Exp. 2, 180 pigs (5.6 kg
      average BW) were used. Treatments for d 0 to 14 were 1) dried skim milk (DSM)
      dried whey-SBM-based control; 2, 3, 4 and 5) Diet 1 with the DSM replaced by
      lactose and flash-dried, spray-dried, and enzyme-modified WG (ModWG), and soybean
      protein isolate (SPI), respectively. All pigs were fed a common diet from d 14 to
      35. For d 0 to 14, pigs fed diets with WG had greater gain/feed than those fed
      SPI (P < .01), and for d 14 to 35, pigs fed spray-dried WG and ModWG had greater
      ADG (P < .04) than pigs fed flash-dried WG. In Exp. 3, 180 pigs (5.7 kg average
      BW) were used. Treatments for d 0 to 14 were 1) DSM-dried whey-SBM-based control;
      2) spray-dried WG and lactose replacing DSM; and 3) spray-dried WG replacing
      SBM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138485
TI  - Insulin resistance, hyperglycemia, and glucosuria in intensively milk-fed calves.
AB  - In intensively milk-fed calves post-prandial glucose (G) and insulin (I)
      concentrations, but not preprandial G concentrations, increased or failed to
      decrease during the growth period, compared with data from calves that were
      progressively weaned. This study was, therefore, designed to investigate G and I
      metabolism in veal calves. Euglycemic-hyperinsulinemic and hyperglycemic clamps
      in the unfed state demonstrated mutual responsiveness of I and G, but revealed a
      relative I resistance. After feed consumption, I resistance was exaggerated, as
      seen by decreased G clearance rates after i.v. G and I administration in fed
      compared with unfed calves. Milk replacer is a source of readily available
      lactose, fat, and protein, the intake of which, on a kilogram.75 basis, gradually
      increased with age. Increased substrate availability and effects of nutrients
      themselves were probably responsible for elevated plasma concentrations of G and
      I and led to I resistance. Additionally, hyperglycemia > 1.5 g/L was followed by
      urinary excretion of G.

PMID- 8138486
TI  - Use of gonadotropin-releasing hormone, estrogen, or a combination to increase
      releasable pituitary luteinizing hormone in early transitional mares.
AB  - A lack of pituitary LH stores has been implicated as the cause of seasonal
      anestrus and failure to ovulate during the spring transition period in mares. In
      this experiment, 40 mares were used to study the effects of GnRH, estrogen, and
      an estrogen-GnRH combination on increasing releasable pituitary LH. Mares were
      stratified based on their ability to secrete LH in response to a 950-micrograms
      challenge of GnRH (n = 10 per group) and then assigned to one of four treatment
      groups: 1) controls, given no treatment; 2) 1 mg of estradiol-17 beta in oil i.m.
      daily for 8 d; 3) 200 micrograms of GnRH analogue des-Gly10, [D-ala6]-LHRH
      ethylamide in saline i.m. twice daily for 8 d; or 4) estradiol for 4 d then
      estradiol plus GnRH for four subsequent days. Blood was collected on d 1, 3, 5,
      and 7 of treatment, and serum was assayed for LH. On d 10 after initiation of
      treatment, mares were again challenged with GnRH (950 micrograms), and blood was
      collected for 4 h. Concentrations of serum LH did not vary significantly in
      control, estradiol-treated, or estradiol plus GnRH-treated mares among treatment
      days. In contrast, administration of GnRH alone increased (P < .05)
      concentrations of LH on d 5 and 7. Response to GnRH challenge, as measured by
      area under the LH curve (AUC) and peak LH, was greater (P < .05) for mares
      administered GnRH (7,307.1, 67.6 ng/mL, respectively) and GnRH plus estradiol
      (5,691.4, 60.3 ng/mL) than for mares given estradiol alone (1,519.4, 22.1 ng/mL)
      or no treatment (1,213.8, 19.4 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138487
TI  - Effect of various doses of a gonadotropin-releasing hormone analogue on induction
      of ovulation in anestrous mares.
AB  - One hundred anestrous mares (early February) were injected s.c. with implants
      containing 0, .9, 1.8, 3.6, or 5.4 mg of a GnRH analogue (goserelin acetate) in
      an attempt to induce ovarian cyclicity. Follicular activity and concentrations of
      progesterone and LH were determined every 3 d, or daily during estrus. In treated
      mares that ovulated, the interval to the second ovulation of the season was
      compared to that for an additional group receiving 16 h/d of light beginning
      December 16 (positive controls). Of the mares that did not ovulate in 30 d, eight
      from each dose group were challenged on d 33 or 34 with an i.v. bolus of 950
      micrograms of GnRH. Blood collected at -2, -1, and 0 h before GnRH and at 15, 30,
      45, 60, and 90 min and 2, 3, and 4 h after injection was assayed for serum LH.
      More mares (P < .05) ovulated when given 3.6- (n = 7) or 5.4-mg (n = 6) implants
      than when given .9-mg implants (n = 0) or placebo (n = 0). Mares with initial
      follicles < or = 15 mm in diameter were less (P < .05) likely to ovulate (10 of
      88) than were those with follicles 16 to 20 mm in diameter (5 of 12). Area under
      the curve (AUC) for LH was greater for mares receiving larger doses of GnRH. The
      AUC and peak LH were similar between ovulating and nonovulating mares.
      Luteinizing hormone peaked in all mares on approximately d 12. There was no
      difference (P > .05) in either peak LH or AUC among treatment groups in response
      to the GnRH challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138488
TI  - Lipoprotein lipase and metabolic activities in incubated bovine adipose tissue
      explants: effects of insulin, dexamethasone, and fetal bovine serum.
AB  - An in vitro system was used to study the regulation of lipoprotein lipase (LPL)
      activity in bovine adipose tissue. The utilization of two energetic and lipogenic
      substrates, acetate and glucose, and the activity of glucose-6-phosphate
      dehydrogenase (G6PDH), an enzyme involved in de novo lipogenesis, were also
      studied. Nine nonlactating, nonpregnant Holstein cows were given limited amounts
      of feed for 10 d, then they were overfed for 3 to 5 wk. Samples of perirenal
      adipose tissue were incubated for 24 or 48 h. Insulin (2 mU/mL) increased (P <
      .001) daily glucose and acetate utilization and attenuated (P < .001) the loss of
      G6PDH activity detected after 1 or 2 d of incubation. Dexamethasone (DEX, 10 nM)
      added to the insulin-supplemented medium decreased (P < .02) glucose utilization,
      but it did not change acetate utilization or G6PDH activity. A higher
      concentration of DEX (100 nM) potentiated (P < .004) the ability of insulin to
      attenuate the decrease in G6PDH activity without changing substrate utilization.
      Under basal conditions, LPL activity was decreased by approximately 66% after 2 d
      of incubation. The decline in LPL activity was attenuated by insulin addition (P
      < .02) and was further attenuated (P < .004) by 100 nM of DEX. The addition of
      10% fetal bovine serum alone to the medium had no effect on LPL activity, and
      fetal bovine serum decreased this activity when it was added to the insulin
      supplemented medium.

PMID- 8138489
TI  - Histological populations and atresia of ovarian follicles in postpartum cattle
      treated with an agonist of gonadotropin-releasing hormone.
AB  - Surface and histological changes of ovarian follicles and degree of atresia were
      characterized 3 and 6 d after a treatment with a GnRH agonist (buserelin) in
      postpartum beef cows. Sixteen cyclic cows on d 7 of their estrous cycle and eight
      acyclic cows were used. On d 0 of the experimental period, eight cyclic cows were
      injected with 2 mL of physiological saline and the remaining eight cyclic cows
      and the acyclic cows were injected i.m. with 8 micrograms of buserelin. Ovaries
      were collected 3 or 6 d later (n = 4 cows per group per day). All follicles (>
      1.57 mm) were observed microscopically, measured using routine histological
      techniques, and classified as either nonatretic or atretic, with early or late
      atresia, and grouped into Class 1, 1.57 to 3.67 mm, Class 2, 3.68 to 8.56 mm, or
      Class 3, > 8.56 mm. Buserelin induced formation of new corpora lutea in all cows
      but one (acyclic cow). Class 1 follicles decreased on d 3 but increased on d 6
      (day x treatment, P < .004), whereas those of Class 2 increased (P < .07) on both
      d 3 and 6 after buserelin treatment. However, within Class 2 follicles, we
      detected an increase on d 3 and 6 in the number (P < .01) and proportion (P <
      .07) of atretic follicles, an increase in the number of follicles in late atresia
      on d 6 (day x treatment, P < .03), and a decrease in the number (P < .06) and
      proportion (P < .03) of nonatretic follicles on d 6 (day x treatment).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138491
TI  - Influence of flake thickness on the feeding value of steam-rolled wheat for
      feedlot cattle.
AB  - Seventy-two medium-framed, crossbred steers (348 kg) were used in a randomized
      complete block design performance trial. Experimental diets contained (DM basis)
      6% alfalfa hay, 6% sudangrass hay, 79% wheat, 2% yellow grease, 4% cane molasses,
      and 3% supplement. Treatments were 1) dry-rolled wheat (DRW, density = .52 kg/L);
      2) steam-rolled wheat, coarse flake (SRW-C, density = .39 kg/L); and 3) steam
      rolled wheat, thin flake (SRW-T density = .30 kg/L). Steam processing increased
      amyloglucosidase reactivity of wheat starch by 238 and 287% for SRW-C and SRW-T,
      respectively. Cattle performance was similar (P > .10) for SRW-C and SRW-T. Steam
      processing wheat increased ADG (13.5%, P < .10) and decreased DM intake/gain
      (8.8%, P < .05). Diet NE was precisely as expected for DRW, confirming the
      applicability of tabular NE values. Diet NEm was 3.7% lower (P < .05) for DRW
      than for SRW. The NEm and NEg of SRW were 2.28 and 1.59 Mcal/kg, respectively.
      Twelve Holstein steers (266 kg) were "T" cannulas in the rumen and proximal
      duodenum were used in a completely random design experiment to evaluate treatment
      effects on characteristics of ruminal and total tract digestion. Ruminal
      digestibilities of OM and starch were similar (P > .10) for DRW and SRW.
      Postruminal and total tract digestibility of OM (P < .10) and starch (P < .01)
      were increased with SRW. Dietary DE and ME values were greater (6.1 and 6.6%,
      respectively; P < .10) for SRW than for DRW.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138490
TI  - Whole-tract digesta kinetics and comparison of techniques for the estimation of
      fecal output in steers fed coastal bermudagrass hay at four levels of intake.
AB  - Coastal bermudagrass (Cynodon dactylon [L.] Pers) hay was fed to four ruminally
      cannulated steers (380 +/- 14 kg BW) of evaluate the effects of intake level on
      digesta flow kinetics in a 4 x 4 Latin square design. Forage intakes represented
      50, 70, 88, and 99% of feed voluntarily consumed per animal during a pre
      experimental period. Masticated boli and wet-sieved masticated leaves (ML) and
      stems (MS) retained by a 4.0-mm sieve and feces retained by a .063-mm sieve were
      mordanted with chromium or marked with erbium, ytterbium, or dysprosium,
      respectively. Particle markers and a solution of Co-EDTA were pulse-dosed via the
      ruminal cannula. A continuous infusion of Co-EDTA was later delivered with
      peristaltic pumps. Intake level had no effect (P > .10) on fluid and particle
      passage rate (PR; percentage/hour) of any fractions marked. For all particle
      fractions, increasing intake level caused linear decreases in mean retention time
      (MRT; P < .03 to P < .07) and linear increases in gastrointestinal tract fill
      (FILL; P < .003 to P < .02) and fecal output (FO; P < .001). Estimates of FO and
      DM digestibility from the pulse dose of Cr mordant and continuous infusion of Co
      EDTA did not differ. Kinetic estimates differed in magnitude according to the
      characteristics of the particle fractions marked. Marked feces gave the shortest
      estimate of MRT and the smallest estimate of FILL and FO. Kinetics of ML and MS
      also differed (P < .001), the former having faster PR, shorter MRT, and smaller
      FILL and FO. Use of representative samples of ingested feed should give more
      realistic estimates of digesta kinetics than estimates derived from ingesta
      fractions because kinetics of separated leaf and stem fractions differed.

PMID- 8138492
TI  - Recovery rate and plasma zinc and copper concentrations of steer calves fed
      organic and inorganic zinc and manganese sources with or without injectable
      copper and challenged with infectious bovine rhinotracheitis virus.
AB  - Two experiments were conducted using feeder calves in a randomized block design
      to determine the effects of organic and inorganic sources of Zn and Mn fed pre-
      and posttransit (Exp. 1 and 2) with or without injectable Cu (Exp. 2) on DMI,
      rectal temperature, BW changes, and plasma Zn and Cu concentrations of feedlot
      steers challenged with infectious bovine rhinotracheitis virus (IBRV). In Exp. 1,
      before weaning, all steers and their dams received the following free-choice
      mineral supplements: 1) control (no supplemental Zn or Mn), 2) ZnO+MnO (ZnMnO),
      and 3) Zn methionine+Mn methionine (ZnMnMet). In Exp. 2, 18 d before weaning and
      shipping, steers were allotted into two groups (22 steers/group) and fed 225 mg
      of Zn.steer-1 x d-1 in .9 kg of ground corn as ZnO or ZnMet. Half of the steers
      from each group were injected (s.c.) with 120 mg of Cu from Cu glycinate. Steers
      (Exp. 1 and 2) were weaned and shipped approximately 2,500 km to the feedlot,
      where they received the same supplements in the form of a complete diet for 34 d,
      during which time calves recovered from the stress due to shipment. All steers
      were initially sero-negative to IBRV. On d 34 (d 0 of IBRV), all steers were
      challenged with IBRV and DMI, rectal temperature, and BW change were monitored
      for 28 d.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138493
TI  - Influence of sugary-Brawn2 or dent corn at two forage levels on intake,
      digestion, and milk production by dairy cows.
AB  - Sugary-Brawn2 (su-Bn2) corn endosperm contains higher concentrations of
      watersoluble polysaccharides than dent corn. Eight multiparous Holstein cows
      averaging 48 d in milk and 667 kg BW at trial initiation were in a replicated 4 x
      4 Latin square design with 28-d periods. Only cows in one square were ruminally
      cannulated. Treatments were su-Bn2 or dent corn and 45 or 60% of ration DM as
      alfalfa silage arranged as a 2 x 2 factorial within each square. Diets,
      formulated to contain 19% CP, were fed as total mixed rations twice daily. Intake
      of DM and milk yield averaged 26.8 and 39.9 kg/d, respectively, and were not
      affected by treatment (P > .10). Sugary-Brawn2 corn decreased milkfat percentage
      (3.27 vs 3.45%), particularly for the low-forage diet (3.15 vs 3.40%). Milk
      protein percentage was higher (3.15 vs 3.10%) for low-forage diets but was not
      affected (P > .10) by corn type. Ruminal pH was lower for low-forage diets.
      Feeding su-Bn2 corn decreased ruminal pH only at 4 h after feeding. Total VFA in
      ruminal fluid (millimolar) 6 h after feeding were higher, whereas acetate molar
      percentage and acetate:propionate ratio were lower for su-Bn2 corn. Ruminal in
      situ evaluation of su-Bn2 and dent corn revealed a larger soluble fraction, a
      faster rate of degradation, and higher availabilities of both DM and starch for
      su-Bn2 corn. Ruminal in situ rate of degradation and availability of alfalfa hay
      DM were reduced by su-Bn2 corn. Total tract apparent digestibilities of DM, CP,
      and starch were greater for su-Bn2 diets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138494
TI  - Site of mineral absorption in lactating cows fed high-fat diets.
AB  - Five lactating Holstein cows with ruminal and duodenal cannulas were used in a 5
      x 5 Latin square to determine the site of mineral absorption and effects of
      sources and amount of dietary fat on apparent absorption. Cows were fed (DM, 17.4
      +/- .8 kg/d) chopped alfalfa hay, alfalfa haylage, corn silage, and concentrate
      at 1:1:1:2 (DM) at 12-h intervals. Calcium salts of palm fatty acid distillate
      (CS) or animal-vegetable (AV) fat were 0% (control), 2.5% (low, L), or 5.0%
      (high, H) of the diet DM. After 2 wk of adaptation, duodenal and fecal grab
      samples were collected at 7-h intervals for 5 d and composited by animal. Calcium
      intake increased (P < .05) with high-fat diets (195 vs 170 g/d), whereas Mg
      intake remained unchanged (54.3 +/- 9.0 g/d). Apparent absorption, estimated by
      Cr2O3, was regressed on Ca or Mg intake (grams/day) and fatty acid (FA) intake
      (grams/day). Total absorption of Ca (grams/day) = -37.4 + .264 Ca (P = .07, R2 =
      .14). Ruminal absorption of Mg was independent of FA intake, and magnesium was
      secreted posterior to the duodenum. Total tract Mg absorption (grams/day) was
      described by -7.685 + .464 Mg -.0044 FA (P < .0005, R2 = .46). Fat intake
      decreased (P < .05) total tract Mg absorption, and Ca absorption was decreased by
      high fat compared with low fat intake (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138495
TI  - Effects of mastication on digestion of whole cereal grains by cattle.
AB  - A study was conducted to evaluate the effects of mastication on the physical
      breakdown and ruminal digestion of whole cereal grains by cattle. Three Hereford
      cows (initial BW 557 kg; SD, 17) surgically fitted with ruminal and esophageal
      fistulas were fed 5.5 kg/d (as-fed basis) of whole barley, corn, or wheat in an
      experiment designed as a 3 x 3 Latin square. Eating time and chews per kilogram
      of DM were greater (P < .10) for corn than for barley or wheat. Whole corn was
      substantially damaged after ingestive mastication, and the majority of kernels
      were broken into small pieces. Many barley and wheat kernels showed signs of
      dentition, but most kernels remained intact. Less saliva (P < .10) was added to
      whole wheat than to barley or corn during ingestive mastication. Cattle fed whole
      barley spent twice (P < .10) as long ruminating per kilogram of DM as those fed
      corn, with intermediate times for wheat. Less than 30% of the DM disappeared from
      unmasticated whole grains during 96 h of ruminal incubation. Ingestive
      mastication increased DM digestion to 53, 69, and 66% for barley, corn, and
      wheat, respectively. Mastication alters the kinetics of ruminal digestion of
      unprocessed cereal grains. Combined with the inherent protein and starch
      digestibilities of the grain, mastication affects the type and extent of
      processing required to optimize the utilization of cereal grains by cattle.
      Unlike barley and wheat, corn kernels are extensively damaged during ingestive
      mastication, reducing the need for physical processing.

PMID- 8138496
TI  - Construction of science for animal agriculture.
AB  - Current animal science research is dominated by disciplinary studies that are
      experimentally controlled and statistically analyzed. Research in animal science
      is also placed predominantly within a hierarchy of biological sciences ranging
      through molecular mechanisms, cells, organ systems, organisms, life systems,
      ecosystems, and human systems. In the main, disciplinary and applied animal
      investigations differ from each other only in that they are conducted within
      different biological work boundaries. Both are largely reductionist and often
      fragmentary. Animal science, however, has two sets of constituents, the
      scientific community and external interests, and both are legitimate. External
      interests will judge the research according to how well it contributes to a
      hierarchy of functional and practical knowledge instead of the biological. The
      functional hierarchy of inquiry ranges through validation of ideas; actions;
      tactics of management; strategies and systems of production; agrospheres
      including land and water resources, landscapes, human capital, and community; and
      the anthrosphere including consumers, food product chains, and global markets.
      More interconnection of the biological and biophysical research with functional
      knowledge is needed but may be limited by insufficient theoretical development of
      the new contributing disciplines such as molecular biology, system science, and
      those represented by the functional hierarchy, and recruitment of specialized
      scientists who often lack practical experience in agriculture and the food
      system. Multiple opportunities for intervention of animal agriculture exist, and
      multiple disciplines including the new biological and functional disciplines will
      be needed to provide what will be perceived to be the full scope of animal
      science research.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138497
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM095.

PMID- 8138498
TI  - Rapid communication: diallelic single-stranded conformational polymorphism
      detected in the bovine prolactin gene.

PMID- 8138499
TI  - Influence of simulated photoperiod alteration and induced estrus on reproductive
      performance of spring-born Columbia and Targhee ewe lambs.
AB  - The objective of this study was to test the hypothesis that a combination of
      induced estrus (IE) and melatonin (MEL) would increase reproductive performance
      in breeds characterized by late maturity more than either IE or MEL alone. Spring
      born Columbia (C; n = 161; 188 to 222 d range of age at breeding; 49 to 80 kg
      range of BW at breeding) and Targhee (T; n = 166; 183 to 210 d range of age at
      breeding; 40 to 68 kg range of BW at breeding) ewe lambs were stratified randomly
      by breed to treatments: ambient controls (AC); IE; MEL; and MEL+IE. Melatonin (18
      mg of Regulin) was implanted on September 7. Estrus induction included
      medroxyprogesterone acetate (MAP) pessaries inserted for 12 d and pregnant mare's
      serum gonadotropin (PMSG; 500 IU i.m.) at time of MAP removal. Ewe lambs were
      placed into two pens with five rams per pen by breed. Targhee ewes lambed at an
      increased rate with IE vs no IE (84.5 vs 67.9%; P < .01) and tended to lamb at an
      increased rate with MEL vs no MEL (82.5 vs 70.6%; P = .07). The 92.7% lambing
      rate observed in the Targhee ewe lambs for the combined treatment (MEL+IE) was
      slightly higher than an additive effect but the interaction between IE and MEL
      was not significant (P = .24). By contrast, none of the treatments altered (P =
      .5) lambing rate, number of lambs born, or number born alive for Columbia ewe
      lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138500
TI  - Technical note: detection of bias in genetic predictions.
AB  - The theoretical development of a procedure to detect bias in genetic predictions
      is presented. The procedure is based on the expectation of three statistics.
      These statistics detect bias by identifying systematic, unexpected change in
      subsequent analyses. Expectations of the following statistics were obtained:
      linear correlation coefficient between subsequent predictions, linear regression
      of recent (more accurate) on previous (less accurate) genetic prediction, and
      variance of the genetic prediction difference (recent minus previous genetic
      prediction). Deviations from these expectations can be used to indicate bias. The
      covariance between subsequent BLUP of genetic value is shown to equal the
      variance of the early estimate, implying that the expected value of the
      regression of recent on previous genetic prediction equals 1 regardless of the
      distribution of the observations and predictions. Also, the expected value of the
      linear correlation coefficient between subsequent genetic predictions equals the
      square root of the ratio of the means of the square of accuracy values. The
      expected value of the variance of the genetic prediction difference was shown to
      be equal to the difference between prediction error variances.

PMID- 8138501
TI  - A bioeconomic model for comparing beef cattle genotypes at their optimal economic
      slaughter end point.
AB  - A bioeconomic model of a feedlot was developed for the comparison of beef cattle
      genotypes under specified management and marketing conditions. The optimization
      behavior of commercial feedlot managers is incorporated into the model using
      optimum economic rotation theory. The days spent in the feedlot (rotation) by a
      group of animals are derived using this theory so as to maximize an objective
      function. Differences among breeds in the present value of profits from a single
      rotation, expressed per animal, represent the expected price premium paid for a
      feeder animal of a particular breed. Feed requirements and growth rates for a
      genotype are predicted over time for a specified diet from estimated mature size.
      Estimates of carcass fatness over time as a function of the energy content of the
      diet and estimates of dressing percentage over time are used for each genotype. A
      base model is described that incorporates biological parameters estimated for 11
      breeds from a major breed comparison experiment and uses prices of inputs and
      outputs for Ontario feedlots. Sensitivity of the model to these biological and
      economic assumptions is shown. When breeds are compared at constant days fed,
      weight, or fat depth slaughter points, rankings are inconsistent, relative to
      those when each breed is slaughtered at its optimal economic point. The model can
      be used to establish appropriate slaughter end points for comparing beef cattle
      breeds and crosses and to evaluate breeding objectives for feedlot traits in
      genetic improvement programs.

PMID- 8138502
TI  - Effects of dietary energy during gestation and lactation on reproductive
      performance of sows: a cooperative study. S-145 Committee on Nutritional Systems
      for Swine to Increase Reproductive Efficiency.
AB  - A cooperative experiment involving 999 litters was conducted at seven stations to
      assess the reproductive performance of gilts and sows fed different levels of
      energy during gestation and lactation (21 d) for three consecutive parities.
      Treatments consisted of two gestation (G) and two lactation (L) diets in a 2 x 2
      factorial arrangement. Gestation treatments were diets fed to provide normal (5.9
      Mcal/d, NG) or high (7.4 Mcal/d, HG) energy intake; lactation treatments were
      diets that contained 0 (NL) or 9% added fat (HL). Sows were provided ad libitum
      access to feed during the lactation period. Feeding the higher energy level
      during gestation increased pig birth weight (P < .01) and pig weight gain to
      weaning (P < .01). Sows that had been fed the higher level of energy during
      gestation (HG) ate less feed during lactation (P < .01) and lost more weight
      during lactation (P < .01). Increasing lactation energy intake by adding fat
      resulted in greater pig weight gains to 21 d of age (P < .01). Sows fed the HG-NL
      combination had fewer pigs on d 21 than all other treatment groups (G x L; P <
      .01). There was a G x L x parity interaction (P < .05) for days to estrus after
      weaning. Sows on the NG-HL or HG-NL treatments had increased days to estrus in
      Parity 1 (P < .05), whereas those on the NG-NL treatments had increased days to
      estrus in Parities 2 and 3 (P < .05). The HG-HL treatment minimized days to
      postweaning estrus during the three-parity study.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138503
TI  - The behavioral component of the ram effect: the influence of ram sexual behavior
      on the induction of estrus in anovulatory ewes.
AB  - The objective of this study was to test whether the sexual behavior of the ram
      affects the ram effect. Rams exhibiting either high (HP) or low (LP) levels of
      sexual performance (on the basis of serving capacity tests) were exposed to 89
      anestrous ewes for 28 d. Thirty-two anestrous ewes were not exposed to rams. The
      objective of this study was to compare the efficacy of estrus induction by HP (n
      = 4) vs LP (n = 4) rams. Plasma progesterone concentration was used as an index
      of ovarian activity. Groups of ewes were exposed to either an HP or an LP ram in
      a .32-ha pasture. Courtship behaviors of rams were recorded for 6 h on the
      initial day of exposure and for 30-min periods on alternate days thereafter. A
      greater percentage of ewes exposed to HP rams ovulated (95%) compared with ewes
      exposed to LP rams (78%) (P < .02). On the 1st d of exposure, the HP rams
      exhibited more courtship behavior and spent more time near the ewes (P < .04).
      The HP rams spent more time within 1 m of ewes during the 28-d exposure. There
      were no differences in the amount of contact with rams (LP or HP) between rise in
      progesterone indicate of ovulation tended to occur earlier (P = .06) in ewes
      penned with HP rams. A greater percentage of ewes exposed to LP rams (P = .03)
      had early elevations of progesterone with no concurrent sexual behavior. These
      data imply that in addition to a pheromone the sexual behavior of the ram may be
      important in initiating ovarian cycle activity.

PMID- 8138504
TI  - Preweaning growth of Yorkshire, Hampshire, and Landrace pigs.
AB  - Individual pig growth curves were derived on 445 Yorkshire, 323 Hampshire, and
      316 Landrace boars and gilts. The range in age was from 1 to 35 d and these
      growth curves were linear. The regression parameters (x- and y-intercepts, and
      slopes) were different among the three breeds, and differences between boars and
      gilts were found in the Yorkshire breed for the y-intercept and slope and in the
      Landrace breed for the y-intercept and slope and in the Landrace breed for the y
      intercept. An additional 130 Yorkshire, 126 Hampshire, and 96 Landrace boars and
      gilts were used to evaluate the effectiveness of adjustments that were additive,
      multiplicative, additive-multiplicative, or based on the x- and y-intercepts.
      Effectiveness was evaluated in terms of accuracy, equality of variance, and
      practical application. The multiplicative adjustments were the most effective in
      the Hampshire breed and the average of the additive and multiplicative
      adjustments was the most effective in the Yorkshire breed. In the Landrace breed
      none of the four methods evaluated produced a credible adjusted 21-d weight. From
      an industry standpoint this study suggests the need for breed-specific specific
      adjustments, and in some breeds this may have to be extended to sex-specific
      adjustments.

PMID- 8138505
TI  - Palmitate esterification and glycerophosphate acyltransferase activity in adipose
      tissue of growing lambs.
AB  - The purposes of this study were to determine the effects of BW in growing lambs
      on rates of palmitate esterification (PE) and activity of glycerophosphate
      acyltransferase (GPAT) in subcutaneous and intermuscular adipose tissue in vitro
      and to determine the relationship between these in vitro measurements and carcass
      lipid accretion. At 37, 49, 60, and 71 kg of live weight, nine, nine, eight, and
      seven Columbia-Rambouillet-cross ewe lambs, respectively, were slaughtered and
      adipose tissue was dissected for glycerolipid biosynthesis assays. One-half of
      each carcass was boned, and carcass soft tissue lipid was measured. In both
      adipose tissues, PE and GPAT activity were highest at 37 kg (P = .0001); the
      greatest accumulation of carcass fat occurred between 37 and 49 kg (P = .0001).
      Differences in PE and GPAT were less well marked between 49-, 60-, and 71-kg
      lambs, but both were generally decreased with increased BW. Significant R2 from
      regressions of mass and percentage of carcass fat on either PE, GPAT, or steady
      state glycerolipid synthesis (GLS) were from .39 to .44 (PE), .40 to .58 (GPAT),
      .50 to .75 (GLS), and .60 to .77 (PE, GPAT, and GLS combined). Changes in PE,
      GPAT, and GLS with BW were consistent with changes in rates of carcass fat
      accretion, which indicated a close relationship between glycerolipid biosynthesis
      in vitro and lipid deposition in vivo in growing-finishing lambs.

PMID- 8138506
TI  - Current merchandising practices and characteristics of beef wholesale rib usage
      in three U.S. cities.
AB  - Packers/processors, supermarket meat managers, and restaurant meat purchasers
      were surveyed to determine industry utilization of the beef wholesale rib. Nine
      packer/processors representing > 52% of the U.S. steer-heifer slaughter reported
      that more than two-thirds (68.5%) of the ribs were wholesaled as ribeye, lip-on
      (IMPS 112A) subprimals and that its predominance in the market makes it the
      standard for pricing. For merchandising variations of this cut (e.g., ribeye, lip
      off), packer prices are adjusted to lip-on bases according to the relative yield.
      Excess fat was the most common complaint about ribeye steaks, reported by 78% of
      the packer/processors. In particular, 71% of them reported the "kernel" fat near
      the center of a ribeye steak between the longissimus and spinalis dorsi muscles
      is quite difficult to trim out and represents the greatest problem in
      merchandising. Forty-two percent of supermarket meat managers and 58% of
      restaurant meat purchasers thought the fat content of beef ribeyes discouraged
      consumers from purchasing all beef. Kernel fat was specifically cited by 36% of
      the restaurateurs. Alternative merchandising strategies should be employed to
      minimize the negative value effects of kernel fat. Even with excess fat being a
      concern to approximately half of the beef rib buyers, most still bought lip-on
      ribeyes and trimmed excess fat away. Apparently, they made this choice of lower
      price per weight, even though price per trimmed serving might be similar to lip
      off ribeyes. Excess fat is being transported from packer/processor to buyers in
      the form of lip-on ribeyes because of the price relationships.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8138507
TI  - Composition of the beef wholesale rib.
AB  - Wholesale ribs (n = 40) were dissected to determine composition from anterior to
      posterior end. There were much greater differences in tissue amounts from
      different anatomical locations within the wholesale rib than between wholesale
      ribs from carcasses of different USDA yield grades. Kernel fat (seam fat between
      the longissimus and spinalis dorsi muscles) was found in considerably higher
      amounts in the 7th, 8th, and 9th rib bone sections. Removal of the lip from IMPS
      112A decreased the separable fat content of ribeyes by approximately 46%. This
      large decrease in fat could make the ribeye more appealing to today's consumer.

PMID- 8138508
TI  - Early onset psychopathology and the risk for teenage pregnancy among clinically
      referred girls.
AB  - OBJECTIVE: To investigate whether early onset DSM-III depressive and conduct
      disorders and historical/familial variables increased the risk of teenage
      pregnancy among clinically referred girls, whose referral was unrelated to their
      reproductive status. METHOD: The sample of 83 girls, 8 to 13 years old at study
      entry, were participating in a longitudinal investigation of childhood-onset
      psychiatric disorders. They were repeatedly evaluated during an interval of up to
      12 years. RESULTS: Twenty-nine girls had at least one pregnancy, and 25 had their
      first pregnancies as teenagers (< or = 18 years old). Several variables that
      predicted earlier age at first pregnancy in longitudinal univariate analyses
      became nonsignificant in the multivariate model. In the final model, childhood or
      adolescent onset conduct disorders (but not depressive disorders), and race were
      significantly associated with teenage pregnancy. Among the girls with conduct
      disorders, 54.8% became pregnant teenagers versus 12% of the rest, and 56% of the
      black adolescents versus 12% of the rest, had teenage pregnancies. CONCLUSIONS:
      After adjusting for race, early onset conduct disorder represents a risk factor
      for teenage pregnancy among psychiatrically referred girls. The mechanisms may
      entail behavioral dysregulation, delay in social-cognitive development, and
      misinformation about reproductive issues. Such girls may benefit from therapeutic
      and educational interventions to delay childbearing.

PMID- 8138509
TI  - Children's descriptions of their firesetting incidents: characteristics and
      relationship to recidivism.
AB  - OBJECTIVE: The primary purpose of the study was to identify characteristics of
      children's firesetting incidents and examine the relationship of reported
      characteristics to psychopathology and firesetting history. METHOD: A sample of
      95 firesetters were interviewed using the Fire Incident Analysis for Children
      (FIAC). Other child or parent measures were obtained reflecting behavioral
      correlates and risk factors for firesetting at initial assessment, and
      firesetting history measures at 2-year follow-up. RESULTS: Access to
      incendiaries, lack of child remorse and parental consequences, and motives of
      curiosity and fun were commonly reported characteristics. Certain firesetting
      characteristics were associated with follow-up recidivism. Repeat versus single
      incident firesetters at initial assessment were similar in firesetting
      characteristics but differed in measures of psychopathology and follow-up
      recidivism. CONCLUSIONS: Children can report on personal and environmental
      details of their firesetting incidents, which may help to identify those children
      most at-risk for setting an additional fire. The findings bear implications for
      understanding firesetting risk-assessment measures, the role of specialized child
      interviews, and potential predictors of firesetting recidivism among children.

PMID- 8138510
TI  - Moral-emotional responsiveness: a two-factor domain of conscience functioning.
AB  - OBJECTIVE: The purpose of this study was to assess the progression in development
      of moral-emotional responsiveness in children and adolescents and to examine the
      relationship of this progression with previously identified stages of
      conceptualization of conscience. METHOD: Using three semistructured questions
      from the Stilwell Conscience Interview, 132 normal volunteers between the ages of
      5 and 17 years were assessed regarding comprehension of their emotional responses
      to moral stimuli. RESULTS: Rational analysis of the responses identified six
      items; each item was scaled for complexity into five stages. Factor analysis of
      the six items revealed two factors: moral-emotional responsiveness 1 contained
      items relating to external anxiety, internal anxiety, and mood; more-emotional
      responsiveness 2 contained items relating to the restoration of
      psychophysiological equilibrium through the processes of reparation and healing.
      Differences between conceptualization stages, with the moral-emotional
      responsiveness factors serving as dependent variables, were accounted for by
      stage differences in age and the positive correlations between the moral
      emotional responsiveness factors and age. CONCLUSIONS: Moral-emotional
      responsiveness is a two-factor domain of the conscience. The findings provide
      additional developmental guidelines for assessing conscience development and
      functioning both in clinical practice and in research.

PMID- 8138511
TI  - An expanded concept of countertransference.

PMID- 8138512
TI  - Antidepressant mechanisms.

PMID- 8138513
TI  - Safety of clonidine and nortriptyline.

PMID- 8138514
TI  - Bupropion and compulsive behavior.

PMID- 8138515
TI  - Outcome of ADHD.

PMID- 8138516
TI  - Medical student attitudes toward child psychiatry.

PMID- 8138517
TI  - Developmental psychopathology and neurobiology of Tourette's syndrome.
AB  - OBJECTIVE: The authors present a model of the developmental psychopathology and
      neurobiology of Tourette's syndrome that provides a framework for ongoing
      research and treatment. METHOD: The model is based on clinical experience and a
      selective review of relevant scientific literature. RESULTS: During the past
      decade, Tourette's syndrome and related conditions have emerged as model
      disorders to study the interplay of genetic, neurobiological, psychological, and
      environmental factors during development. Although prevention and treatment are
      paramount, the effectiveness of these interventions depends on the quality and
      extent of our knowledge. Programmatic research combined with sustained clinical
      care has led to advances in our knowledge of the natural history of these
      disorders over the course of development and glimpses of the pathophysiologic and
      psychopathological mechanisms that mediate their expression in vulnerable
      persons. CONCLUSIONS: In the future, we expect that our understanding will extend
      from the molecular level of how specific genes and epigenetic factors confer and
      mediate vulnerability to an understanding of why certain symptoms emerge when
      they do in the course of central nervous system development.

PMID- 8138518
TI  - Detrimental effects of prenatal cocaine exposure: illusion or reality?
AB  - OBJECTIVE: The primary purpose of this study is to investigate the impact of
      prenatal cocaine exposure, while controlling for other factors that influence
      infant outcome. METHOD: These preliminary data are from an ongoing prospective
      study of prenatal cocaine and/or crack exposure. Detailed information is
      collected about the use of cocaine, crack, alcohol, tobacco, marijuana, and other
      drugs during each trimester of pregnancy. RESULTS: Women who use cocaine and/or
      crack during pregnancy differ from those who do not. The women who use cocaine
      are older, more likely to be black, and less likely to be married. They also use
      more tobacco, alcohol, and marijuana during pregnancy than do nonusers of
      cocaine. When these differences between the exposure groups are controlled,
      preliminary analyses indicate there is no significant effect of prenatal cocaine
      use on infant growth and morphology. CONCLUSIONS: Future research needs to
      address the effects of prenatal cocaine and/or crack exposure on central nervous
      system development and on the long-term development of exposed offspring.

PMID- 8138519
TI  - Prescribing practices of outpatient child psychiatrists.
AB  - OBJECTIVE: This study was designed to assess outpatient child psychiatrists'
      prescribing practices. METHOD: Of 1,422 outpatients in two public, university
      affiliated settings in New York and Ohio, the charts of 146 medicated and 126
      nonmedicated randomly selected patients were reviewed for demographic variables,
      DSM-III-R diagnoses, medications prescribed, and charted prescription rationales.
      RESULTS: Fifteen percent of the 800 outpatients seen in a 1-month period in New
      York, and 19% of the 626 outpatients seen in a 1-year period in Ohio were
      prescribed medication. Patients medicated by clinic psychiatrists were
      significantly more likely than nonmedicated patients to be psychotic and to have
      been hospitalized previously, and significantly less likely to have adjustment
      disorder. Using standards employed by drug utilization review committees,
      medications were prescribed appropriately in approximately 90% of cases. Of
      concern, 65% of patients given antipsychotics in New York and 67% in Ohio were
      not psychotic; the primary target symptom in such cases was aggression.
      CONCLUSIONS: Prescribing practices appeared to be appropriate, although the use
      of antipsychotic medications in nonpsychotic children is a concern for the field
      of child psychiatry. The strong similarity of practices in two independent and
      geographically remote sites suggests the findings are generalizable to providers
      in other public, university affiliated settings.

PMID- 8138520
TI  - The efficacy of psychoanalysis for children with disruptive disorders.
AB  - OBJECTIVE: This paper describes a chart review of 763 cases of child
      psychoanalysis and psychotherapy at the Anna Freud Centre, and illustrates its
      usefulness by examining predictors of treatment outcome in children with
      disruptive disorders. METHOD: 135 children and adolescents with a principal
      diagnosis of disruptive disorder were individually matched with others suffering
      from emotional disorders. Outcome was indicated by diagnostic change and change
      in overall adaptation (clinically significant improvement or return to normal
      functioning). RESULTS: Improvement rates were significantly higher for the
      emotional than for the disruptive group. Within the disruptive group, significant
      improvement was more frequent among children with oppositional defiant disorder
      (56%) than those with attention deficit hyperactivity disorder (36%) or conduct
      disorder (23%). However, 31% of the children terminated treatment within 1 year.
      Of those disruptive children who remained in treatment more than 1 year, 69% were
      no longer diagnosable on termination. Fifty-eight percent of the variance in
      outcome ratings could be accounted for within this group. The crucial variables
      in predicting attrition and symptomatic improvement were found to be quite
      different in the disruptive and emotional groups. CONCLUSION: Although the study
      has several methodological limitations, it does suggest demographic, clinical,
      and diagnostic characteristics of those disruptive children most likely to
      benefit from intensive and nonintensive psychodynamic treatment.

PMID- 8138521
TI  - Home behaviors of children in three treatment settings: an outpatient clinic, a
      day hospital, and an inpatient hospital.
AB  - OBJECTIVE: To compare parents' ratings of home behaviors of three groups of
      children: those entering an outpatient clinic, a day hospital, and an inpatient
      hospital. It was hypothesized that the home behaviors of children starting day
      and inpatient hospital treatment would be rated as significantly more deviant
      than those of children beginning outpatient treatment, and there would be no
      significant differences in behavior ratings of children beginning day and
      inpatient hospital treatment. METHOD: A standardized behavior checklist was
      completed by the primary parent at the time treatment was begun. Scores on four
      factor scales were obtained, and a multivariate analysis of covariance was
      carried out. RESULTS: The hypotheses were partially supported. Children beginning
      day and inpatient hospitalization were seen as more disordered, anxious, and
      aggressive than were those starting outpatient treatment; children starting day
      treatment were reported as more learning disabled than were those in both
      outpatient and inpatient settings; and children entering the inpatient setting
      were perceived as more aggressive than were those in day treatment. CONCLUSION:
      Aggressive behavior and learning disability appear to be determinants of choice
      of treatment setting. The progression from least to most restrictive placement
      was demonstrated for aggressive behavior only.

PMID- 8138522
TI  - Plasma levels and efficacy of imipramine treatment for enuresis.
AB  - OBJECTIVE: To determine the relationship between serum drug level and treatment
      efficacy in enuretic children treated with imipramine (IMI). METHOD: Eighteen
      children with primary nocturnal enuresis recruited from an ambulatory enuresis
      clinic population were the subjects of the study. After a baseline period of 2
      weeks, children received placebo for 1 week followed by treatment with IMI in
      increasing dosages (1.0 mg/kg, 1.5 mg/kg, 2.0 mg/kg, and 2.5 mg/kg), each dosage
      being given for 2 weeks. Steady state IMI and desipramine levels were determined
      in each child for each dosage. Medication response ([drug % dryness-placebo %
      dryness] divided by [100%-placebo % dryness]) was determined for each dosing
      interval. RESULTS: Average dryness increased from 27.8% on placebo to 73% with
      2.5 mg/kg of IMI. The overall correlation between medication response and
      combined serum level was .26 (p < .05). Side effects were monitored throughout
      the study and were found to be rare. CONCLUSIONS: The efficacy of IMI over
      placebo in reducing the frequency of nocturnal enuresis in children was
      confirmed. Efficacy was moderately but significantly related to increasing mg/kg
      dose. A higher serum level tended to be associated with a better response, but
      there was at least 700% variation in serum level between subjects at every
      dosage. Monitoring serum levels of imipramine in children with idiopathic
      functional nocturnal enuresis treated with that medication has a limited but real
      usefulness in clinical management.

PMID- 8138523
TI  - Clozapine treatment in very early onset schizophrenia.
AB  - Very early onset schizophrenic patients only partially benefit from conventional
      antipsychotic treatment and are at increased risk for developing tardive
      dyskinesia (TD). Clozapine, which lacks extrapyramidal side effects including TD,
      has been proved effective for adult schizophrenic patients who are resistant to
      other neuroleptics. Clozapine, therefore, may offer an alternative treatment for
      these patients. The authors report four successful trials of clozapine in
      children aged 10 to 12 years old with schizophrenia, the youngest group reported
      on to date, who were unresponsive to conventional neuroleptic treatment.

PMID- 8138524
TI  - Children of disaster in the second decade: a 17-year follow-up of Buffalo Creek
      survivors.
AB  - OBJECTIVE: To conduct a long-term follow-up of child survivors of a devastating
      human-caused disaster. METHOD: Child survivors (2-15) of the Buffalo Creek dam
      collapse, first evaluated in 1974, 2 years postdisaster, were reevaluated 17
      years postdisaster when they were adults. Of the original 207 children, 99 were
      located and reevaluated using ratings on the Psychiatric Evaluation Form, the
      Impact of Event Scale, and the SCL-90 and lifetime and current diagnoses from the
      Structured Clinical Interview for DSM-III-R. RESULTS: Ratings of psychiatric
      symptoms at the two points in time showed significant decreases in overall
      severity ratings and in anxiety, belligerence, somatic concerns, and agitation. A
      few symptoms, not present in the child sample, increased over time (substance
      abuse, suicidal ideation). The current rate of disaster-related post-traumatic
      stress disorder (PTSD) was 7%, down from a postflood rate of 32%. There were no
      differences by age group in current psychological status; however, women
      evidenced more PTSD-related symptoms than did men. All current PTSD cases were
      women. Comparisons with similar subjects from a nonexposed community showed no
      differences. CONCLUSIONS: The findings indicated that the children studied,
      although having shown earlier effects, had "recovered" from the event by the time
      of long-term follow-up.

PMID- 8138525
TI  - Children exposed to disaster: I. Epidemiology of post-traumatic symptoms and
      symptom profiles.
AB  - OBJECTIVE: To determine the range and severity of post-traumatic stress disorder
      (PTSD) symptoms exhibited by children after exposure to a natural disaster.
      METHOD: Three months after Hurricane Hugo struck Berkeley County, South Carolina,
      5,687 school-aged children were surveyed about their experiences and reactions
      related to the storm. Self-reports of PTSD symptoms were obtained by use of a
      PTSD Reaction Index. RESULTS: Significant variation in the prevalence of PTSD
      symptoms was found across race, gender, and age groups. Self-reported symptoms
      were used to derive a post-traumatic stress syndrome classification according to
      DSM-III-R guidelines for the diagnosis of PTSD. More than 5% of the sample
      reported sufficient symptoms to be classified as exhibiting this post-traumatic
      stress syndrome. Females and younger children were more likely to receive this
      classification. At the symptom level, females reported more symptoms associated
      with emotional processing and emotional reaction to the trauma. Males were more
      likely to report symptoms related to cognitive and behavioral factors. Younger
      children were more likely to report symptoms overall. CONCLUSIONS: Children
      exposed to a high magnitude natural disaster report sufficient symptoms to
      establish a DSM-III-R derived classification of a PTSD syndrome. Differences
      between gender, age, and race groups appear to be related to differential risk of
      exposure, reporting biases, as well as a differential risk for developing post
      traumatic symptoms.

PMID- 8138526
TI  - Children exposed to disaster: II. Risk factors for the development of post
      traumatic symptomatology.
AB  - OBJECTIVE: To examine the influence of subject and exposure variables on the
      development of post-traumatic stress disorder (PTSD) symptoms and syndrome in
      children exposed to disaster. METHOD: Three months after Hurricane Hugo, 5,687
      school-aged children were surveyed about their experiences and reactions to the
      hurricane. Self-reports of PTSD symptoms were obtained by use of a PTSD Reaction
      Index. RESULTS: The presence of PTSD symptoms was strongly related to children's
      reported severity of the hurricane, degree of home damage sustained, and
      continued displacement; however, children's level of trait anxiety and their
      reported emotional reactivity during the hurricane were more strongly related to
      the presence of PTSD symptoms than were the exposure factors. Different sets of
      risk factors appeared to differentially influence the development of the three
      DSM-III-R PTSD symptom clusters. Little evidence for a differential effect of the
      risk factors between females and males and younger and older children was found.
      CONCLUSIONS: Level of trait anxiety appears to be the single strongest risk for
      the development of severe post-traumatic reactions. The higher rate of post
      traumatic symptoms in females and younger children in combination with the
      absence of differential reaction to the risk factors suggests that females and
      younger children are more likely to develop posttraumatic reactions following a
      disaster.

PMID- 8138527
TI  - Crystallization and preliminary X-ray studies on pseudoazurin from Achromobacter
      cycloclastes IAM1013.
AB  - New crystals of a blue copper protein, pseudoazurin from denitrifier
      Achromobacter cycloclastes IAM1013, have been obtained by means of vapor
      diffusion with ammonium sulfate as a precipitant at pH 6.0 and 4 degrees C. The
      crystals belong to the orthorhombic system, space group P2(1)2(1)2(1), with unit
      cell dimensions of a = 56.69(2), b = 61.53(2), and c = 30.20(1) A. The asymmetric
      unit includes one molecule of pseudoazurin with a Vm value of 2.04 A3/Da. The
      crystals are so stable against X-ray irradiation that a complete data set up to
      1.54 A has been collected using a single native crystal. Solution of the
      structure was performed by means of the Patterson search techniques, and the
      current crystallographic R-factor is 17.5% at 3.0 A resolution. Refinement at
      higher resolution is in progress.

PMID- 8138528
TI  - Structural analysis of O-linked sugar chains in human blood clotting factor IX.
AB  - Type and structural analysis of O-linked sugar chains in human blood clotting
      factor IX was performed by the pyridylamination method developed for O-linked
      sugar chains [Kuraya, N. & Hase, S. (1992) J. Biochem. 112, 122-126]. O- and N
      linked sugar chains were released with hydrazine, and then N-acetylated, followed
      by pyridylamination. The type of sugar chain was determined by reducing-end
      analysis of the pyridylaminated (PA-) sugar chains. Sugar chains with PA-GalNAc
      at the reducing terminal and that with PA-Fuc [Nishimura, H. et al. (1992) J.
      Biol. Chem. 267, 17520-17525] were obtained besides known sugar chains with PA
      Glc from the Xyl-Glc-Ser type and those with PA-GlcNAc from asparagine-linked
      sugar chains. The sugar chains with PA-GalNAc were identified as mono- and
      disialyl Gal beta 1-3GalNAc by two-dimensional HPLC mapping. The structure of the
      sugar chain with PA-Fuc was Neu5Ac alpha 2-6Gal beta 1-4GlcNAc beta 1-3Fuc, as
      determined by exoglycosidase digestion, methylation analysis, and Smith
      degradation.

PMID- 8138529
TI  - Electrospray ionization-mass spectrometric analysis of serum transferrin isoforms
      in patients with carbohydrate-deficient glycoprotein syndrome.
AB  - We previously reported that the carbohydrate-deficient glycoprotein (CDG)
      syndrome is an asparagine-N-linked sugar chain transfer deficiency [Yamashita et
      al. (1993) J. Biol. Chem. 268, 5783-5789]. In order to confirm this hypothesis,
      we applied electrospray ionization-mass spectrometric analysis to transferrin
      isoforms purified from patients with the CDG syndrome. Transferrin isoforms
      containing 4, 2, and 0 sialic acid residues, S4, S2, and S0, were separated by
      Mono Q anion exchange column chromatography from serum of a patient with the CDG
      syndrome. The molecular masses of S4, S2, and S0 were determined to be 79,570 +/-
      5, 77,364 +/- 6, and 75,157 +/- 6 Da by electrospray ionization mass spectrometry
      (ESI/MS). The differences between S4 and S2, and between S2 and S0 were both in
      accordance with the molecular mass of a disialylated biantennary sugar chain
      [Neu5Ac alpha 2-->6Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6(Neu5Ac alpha 2-
      >6Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->3)Man beta 1-->4GlcNAc beta 1-
      >4GlcNAc] (2,206 Da), showing that S0 is nonglycosylated, and that S4 and S2
      carry 2 and 1 mol of asparagine-N-linked sugar chains, respectively. The
      nonglycosylated asparagine site of S2 was elucidated to be random by high
      performance liquid chromatography-ESI/MS of a tryptic peptide of reduced and
      pyridylethylated S2.ESI/MS analysis of transferrin purified through one step from
      serum is applicable for a definite diagnosis of the CDG syndrome.

PMID- 8138530
TI  - ATPase activities of the two cross-linked species of actin and myosin.
AB  - We describe cross-linking conditions for myosin subfragment-1 and actin with 1
      ethyl-3-[3-(dimethylamino)propyl]carbodiimide, with which the compositions of
      cross-linked species can be altered. The specific Mg-ATPase activity of cross
      linked subfragment-1 in these preparations was almost the same in spite of the
      differences in the compositions of the cross-linked species. This suggests that
      the two kinds of cross-linked species have almost the same ATPase activity, and
      that the cross-linking at these different sites nearly equally facilitates the
      formation of the strong binding state which accompanies the release of ADP and
      Pi.

PMID- 8138531
TI  - Melittin-binding of troponin C.
AB  - Ca(2+)-dependent interaction between skeletal muscle troponin C and a bee venom
      melittin, which can be regarded as a mimic of the troponin C-binding peptide of
      troponin I, was investigated. Sephadex gel chromatography revealed that melittin
      bound to troponin C irrespective of the presence or absence of Ca2+ in 50 mM KCl
      and 50 mM Tris-HCl, pH 7.5. At high salt concentration, 0.5-1.2 M KCl, melittin
      was removed from apo troponin C but still bound to Ca(2+)-loaded troponin C.
      Hydrophobic affinity chromatography revealed that hydrophobic region(s) appeared
      on the surface of troponin C upon Ca2+ binding but vanished upon Ca2+ release.
      Therefore, at physiological salt concentration, melittin binds to Ca(2+)-loaded
      troponin C by both hydrophobic and electrostatic interactions, and it binds to
      apo troponin C by electrostatic interaction. The midpoint of the fluorescence
      titration curve of troponin C-melittin complex, observed by Trp-19 fluorescence,
      scarcely depended on the concentration of MgCl2. This means Trp-19 of melittin
      detects only the conformational change of troponin C induced by Ca(2+)-binding to
      the low affinity Ca(2+)-binding sites (sites I and II) of troponin C; that is,
      the C-terminal of melittin binds to the N-terminal of troponin C. Fluorescence
      stopped-flow experiments revealed that the time course of Trp-19 fluorescence
      change induced by the Ca(2+)-release from the low affinity Ca(2+)-binding sites
      of troponin C in the complex was biphasic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138533
TI  - Probing the determinants of protein solubility with amino acid modification.
AB  - Chemical modification was used as a probe to study the effect of structural
      features of serum albumin (charge, conformation, surface hydrophobicity, etc.) on
      its solubility behavior in concentrated ammonium sulfate solutions. Four
      different acetylated derivatives of goat serum albumin namely 18% acetylated, 40%
      acetylated, 53% acetylated, and 93% acetylated albumins were prepared. The
      homogeneity of these preparations was established by gel chromatography and
      polyacrylamide gel electrophoresis. Hydrodynamic data on the Stokes radius of
      native and acetylated albumins suggested gradual change in conformation on
      increasing modification. Solubility experiments performed in concentrated
      ammonium sulfate solutions at pH 7.0 and at 30 degrees C showed a slight decrease
      in salting-out parameter, Ks, up to 40% modification, whereas a significant
      decrease was obtained at higher modification. However, the salting-out parameter,
      beta, decreased monotonously. Similar decrease in these parameters was also
      observed with different modified albumins at other pH values viz. pH 5.5, 4.5,
      and 3.6. From these results we conclude that the decrease in solubility of serum
      albumin on increasing modification was primarily due to change in conformation.

PMID- 8138532
TI  - Increase in the amount of elongation factor 2 in rat liver by peroxisome
      proliferators.
AB  - The changes in protein phosphorylation during induction and deinduction of
      peroxisome proliferation in rat liver by three types of proliferators were
      studied by in vitro phosphorylation assay. Among the variously phosphorylated
      proteins, an increase during induction and a decrease during deinduction in
      phosphorylation of P100, a cytosolic protein having a molecular weight of 100
      kDa, was most remarkable. The time course of enhancement of phosphorylation by
      the administration of the proliferators, however, was not parallel with
      proliferation of peroxisome but with increase in the liver DNA content. Amino
      acid sequencing of the protein indicated the identity of its N-terminal 17 amino
      acid residues with those of elongation factor 2 (EF2). Increase in the amount of
      EF2 by peroxisome proliferators was confirmed by immunoblotting and this was
      almost parallel with peroxisome proliferation, suggesting that both increase in
      the amount of EF2 and some changes in phosphorylation activities account for a
      large increase in in vitro phosphorylation of EF2 by the administration of
      peroxisome proliferators.

PMID- 8138534
TI  - Uptake of cobalamin by Euglena mitochondria.
AB  - Cobalamin uptake by Euglena mitochondria is a biphasic process, consisting of
      energy-independent cobalamin-binding to mitochondrial membranes and energy
      dependent active transport. The energy-dependent phase of cobalamin uptake is not
      dependent on mitochondrial respiration, but on the presence of ATP within the
      mitochondrial matrix. The dissociation constant of the energy-independent
      cobalamin-binding reaction is estimated to be 0.45 nM. Inhibition of the
      mitochondrial cobalamin uptake by a variety of cobalamin analogues indicates that
      Euglena mitochondria have an absolute requirement for the complete cobalamin
      molecule with an alpha-axial ligand (the cobalt-coordinated nucleotide) and an
      intact b-propionamide side-chain. Thus, the Euglena mitochondrial cobalamin
      uptake system is highly specific for the cobalamin structure. The cobalamin taken
      up by the Euglena mitochondria cannot be exchanged with exogenous cobalamin. All
      of the mitochondrial cobalamin is associated with three proteins with molecular
      masses of > 700,000 (16.3%), 160,000 (7.4%), and 35,000 (76.3%). They occur in
      the soluble fraction of mitochondria, suggesting that these cobalamin-binding
      proteins or cobalamin-dependent enzymes play an important role in cobalamin
      accumulation and metabolism within the mitochondria.

PMID- 8138535
TI  - Purification, some properties, and primary structure of a base non-specific
      ribonuclease from oyster (Crussdstrea grigus).
AB  - A ribonuclease (RNase Oy) was purified to homogeneity on SDS-PAGE from the
      homogenate of oyster (Crussdstrea grigus). The apparent molecular weight
      estimated from SDS-PAGE was ca. 28 kDa. The pH optimum of the RNase was 5.0. The
      RNase released mononucleotides from RNA in the order of 3'-GMP, 3'-AMP, and 3'
      UMP. The complete amino acid sequence of RNase Oy was determined, mostly by
      analyzing the peptides generated by BrCN cleavage or digestion by
      lysylendopeptidase, staphylococcal V8 protease, and alpha-chymotrypsin. The
      molecular weight of the protein moiety of RNase Oy deduced from the sequence was
      24,359. The sequence of RNase Oy contained two typical histidine residues in
      segments common to the active site of RNase T2 family enzymes. The locations of
      six half cystine residues among eight were almost superimposable on those of four
      known plant RNases of RNase T2 family. The sequence homology between RNase Oy and
      five fungal and four plant RNases amount, to 43-56 amino acid residues. The amino
      acid sequence of the N-terminal part of RNase Oy is more similar to those of
      plant RNases than to those of fungal RNases. This RNase is the first RNase T2
      family RNase from mollusc whose primary structure has been elucidated.

PMID- 8138536
TI  - Magnesium regulates both the nucleotide binding and the enzyme activity of
      isolated chloroplast coupling factor 1.
AB  - The inactivation and the activation of the ATPase of isolated CF1 as assayed by
      the hydrolysis of ATP in 10 s depended on prior binding of ADP-Mg and ATP-Mg. The
      effects of Mg2+ on the nucleotide binding kinetics were studied by monitoring the
      time courses of UV spectral changes induced by the interaction between CF1 and
      ADP or ATP using a rapid-scan spectrophotometer equipped with a stopped-flow
      cell. The apparent rate constant of ADP binding to the two high-affinity sites on
      CF1 (designated sites B and C in the previous report [Hisabori, T. & Sakurai, H.
      (1984) Plant Cell Physiol. 25, 483-493]) was drastically increased by prior
      binding of Mg2+ to CF1, but not ATP. The inhibitory effect of Mg2+ was attributed
      to a marked increase in kon for the inhibitory ADP binding at the high-affinity
      sites induced by the previous binding of Mg2+ to the enzyme. The location of site
      B is suggested to be on the beta subunit based on the difference spectral change
      induced by binding of the ADP analog 2',3'-O-(2,4,6-trinitrophenyl)ADP to CF1.

PMID- 8138537
TI  - Improved method for expression of Kunitz-type serine proteinase inhibitor domain
      of beta-amyloid protein precursor in Escherichia coli and characterization of
      disulfide bonds of the product.
AB  - Kunitz-type serine proteinase inhibitor (KPI) domain of Alzheimer's disease
      related beta-amyloid protein precursor (APP) was expressed in Escherichia coli as
      a fusion protein with a truncated form of Staphylococcus protein A. The fusion
      protein was purified from the cell culture medium using an IgG Sepharose column.
      The KPI domain was separated from the protein A portion by cleavage with human
      alpha-thrombin at the engineered recognition sequence, followed by purification
      on IgG Sepharose and reversed-phase HPLC columns. The recombinant KPI domain
      strongly inhibited trypsin; the inhibition constant (Ki) for bovine trypsin was
      2.5 x 10(-11) M, comparable to those of the secreted forms of APP with the KPI
      domain. The recombinant protein contained three intramolecular disulfide bonds,
      which were determined to be located between Cys-6 (C1) and Cys-56 (C6), Cys-15
      (C2) and Cys-39 (C4), and Cys-31 (C3) and Cys-52 (C5) of the recombinant KPI
      domain, respectively. These positions are highly homologous to those of disulfide
      bonds in bovine pancreatic trypsin inhibitor. The trypsin-inhibitory activity of
      the recombinant protein was abolished by preincubation with 0.4 mM dithiothreitol
      under non-denaturing conditions. By this mild reduction, all the disulfide bonds
      were completely cleaved. These results clearly indicate that the disulfide bonds
      play an important role in the function of the KPI domain of APP.

PMID- 8138538
TI  - Heparin as an inducer of hepatocyte growth factor.
AB  - Hepatocyte growth factor (HGF) has mitogenic and unique morphoregulatory
      functions, and is considered to act as a hepatotrophic and a renotrophic factor
      for regeneration of the liver and kidney subjected to various insults. We have
      now obtained evidence that heparin is a potent inducer of HGF production. The
      addition of heparin to a culture of MRC-5 human embryonic lung fibroblasts
      increased the HGF concentration in the conditioned medium, in a dose-dependent
      manner. The maximal stimulation was obtained at 1 microgram/ml heparin and
      stimulation was 4-fold compared to control cultures. The rate of HGF synthesis in
      MRC-5 cells, as measured by pulse-labeling with [35S]methionine, and subsequent
      immunoprecipitation of HGF from both conditioned medium and a cell lysate, was 3
      4-fold stimulated by 1 microgram/ml heparin, whereas heparin apparently had no
      significant effect on the HGF mRNA level. The stimulatory effect of heparin on
      HGF production was evident in various types of cells, such as MRC-9, IMR-90, and
      WI-38 human embryonic lung fibroblasts, human skin fibroblasts, HL-60 human
      promyelocytic leukemic cells and human umbilical vein endothelial cells. In
      addition to heparin, heparan sulfate also stimulated HGF production, albeit to a
      lesser extent than heparin; 1.7-fold stimulation with 2 micrograms/ml heparan
      sulfate. However, other glycosaminoglycans, such as hyaluronic acid, chondroitin
      sulfate, dermatan sulfate, keratan sulfate, and keratan polysulfate, had no
      stimulatory effect on HGF production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138539
TI  - Role of intramolecular high-mannose chains in the folding and assembly of soybean
      (Glycine max) lectin polypeptides: studies by the combined use of spectroscopy
      and gel-filtration size analysis.
AB  - It was previously reported [Nagai, K. & Yamaguchi, H. (1993) J. Biochem. 113, 123
      125] that intramolecular high-mannose chains are essential for reconstitution of
      soybean lectin from denatured subunits. To obtain more detailed information on
      the role of the intramolecular high-mannose chains in the folding and assembly of
      soybean lectin polypeptides, the effects of asparagine-linked oligosaccharides,
      Man9GlcNAc2Asn (M9-Asn) and Glc1-3Man9GlcNAc2Asn (GM9-Asn), on the reconstitution
      of soybean lectin from denatured subunits were examined by comparison with the
      denaturation features of the lectin with varying concentrations of guanidine
      hydrochloride. The combined use of spectroscopy and size-analysis by gel
      filtration revealed that both the folding and assembly of denatured subunit
      polypeptides were completely prevented in the presence of 300 microM M9-Asn,
      whereas the same concentration of GM9-Asn only interfered with the polypeptide
      assembly, exhibiting no significant effect on the polypeptide folding. These
      results, considered together with those in the previous report, indicate that the
      sugar branch Man alpha 1-2Man-alpha 1-2Man linked to the 3 position of the beta
      mannosyl residue of the high-mannose chains functions in the folding of the
      subunit polypeptides, and that other branches participate in the subunit
      assembly.

PMID- 8138540
TI  - Amino acid sequence of glutathione S-transferase a from guinea pig liver.
AB  - The amino acid sequence of glutathione S-transferase a from guinea pig liver was
      determined. Glutathione S-transferase a was composed of two identical subunits,
      each comprising 218 amino acid residues. The amino acid sequence of glutathione S
      transferase a exhibited 73% homology with that of human glutathione S-transferase
      Ha, 69% with that of rat glutathione S-transferase Ya, and 68% with that of rat
      glutathione S-transferase Yc, which are known to belong to class Alpha. From the
      above result, together with previous observations on its substrate specificity,
      it was concluded that glutathione S-transferase a belonged to class Alpha.

PMID- 8138541
TI  - Crystal structure of RNase T1(Y45W) complexed with 3'AMP and GflpA.
AB  - We have previously reported the crystallization of a mutant RNase T1(Y45W) with a
      synthetic modified trinucleotide ApGflpA [Hakoshima, T. et al. (1990) J. Biochem.
      108, 695-698]. In the present report, we describe the crystal structure refined
      at 2.4 A resolution. During the refinement process, we found that the ApGflpA
      molecule was cleaved at the phosphodiester bond between the 5'-terminal adenosine
      and the subsequent 2'-fluoroguanosine. At the end of the refinement (R = 17.1%),
      it was supposed that the resulting molecules, i.e., 3'AMP and GflpA, were
      separately bound to the enzyme. In the complex structure, the binding-site of the
      enzyme was occupied by the guanine base of GflpA via a similar interaction to
      that of the enzyme complexed with 2'GMP, while the phosphate group of GflpA was
      not bound to the active site. The guanosine adopted the anti orientation on the
      glycosyl torsion angle with a C2'-endo-C3'-exo sugar pucker. This conformation
      resulted in the phosphate group protruding from the active site. The phosphate
      group of 3'AMP was bound to the active site of the enzyme and oriented itself
      toward the solvent region. This orientation was different from that of 2'AMP
      bound to the RNase T1(Y45W).

PMID- 8138542
TI  - Transcription factors positively and negatively regulating the Na,K-ATPase alpha
      1 subunit gene.
AB  - A cDNA clone encoding a zinc finger protein (AREB6) was isolated from a HeLa cell
      expression library using a positive regulatory element (-102 to -58) of rat Na,K
      ATPase alpha 1 subunit gene (Atp1a1) as a probe. The clone is apparently an
      extended one of Nil-2-a originally isolated as a negative regulator of
      interleukin 2 gene [Williams, T.M. et al. (1991) Science 254, 1791-1794]. The
      open reading frame encodes 1,124 amino acids. It contains 7 zinc-finger motifs
      arranged in two widely separated clusters. A glutamic acid-rich region is
      observed at the C terminus from residues 989 to 1123. Co-transfection of the
      AREB6 cDNA with Atp1a1 fused to a reporter luciferase gene indicated that the
      AREB6 protein enhances or represses the promoter activity of the gene depending
      on the quantity of cDNA and on the cell type. The mRNA of AREB6 is expressed in
      heart and skeletal muscle, but not in liver, spleen, or pancreas. Genomic
      Southern analysis indicated that the gene encoding AREB6 is present as only one
      copy or two at most. Another cDNA clone obtained by using the same probe was
      identified as HEB [Hu, J.S., Olson, E.N., & Kingston, R.E. (1992) Mol. Cell.
      Biol. 12, 1031-1042]. Co-transfection of the cDNA enhanced or repressed the
      promoter activity of Atp1a1 depending on the cell type.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138543
TI  - Site-directed mutagenesis shows that the conserved cysteine residues of
      histidinol dehydrogenase are not essential for catalysis.
AB  - Histidinol dehydrogenase (HDH) catalyzes two sequential oxidation reactions to
      produce histidine from histidinol via histidinaldehyde. In HDH proteins so far
      reported, two Cys residues are conserved. From the results of the studies on
      Salmonella typhimurium HDH, it has been proposed that one of these two conserved
      Cys residues is involved in the thiohemiacetal formation at the aldehyde
      oxidation step [Grubmeyer and Gray (1986) Biochemistry 25, 4778-4784]. To clarify
      the reaction mechanism, we investigated the role of the conserved Cys residues by
      site-directed mutagenesis in cabbage HDH. Thus, Cys-112, that corresponds to the
      catalytic Cys residue of the Salmonella enzyme, and the other conserved one, Cys
      149, were replaced with Ala, Ser, or Phe. All the Cys-112 mutant HDHs catalyzed
      both the alcohol dehydrogenase and aldehyde dehydrogenase reactions, producing 1
      mol of L-histidine during the reduction of 2 mol of NAD+, as did the wild type
      HDH. Site-directed mutagenesis at Cys-149 did not cause significant changes in
      the catalytic properties, either. These observations, together with the results
      of detailed comparison of the catalytic properties of mutant HDHs, clearly
      indicate that neither Cys-112 nor Cys-149 is involved in the reaction, and ruled
      out the involvement of thiohemiacetal formation in the histidinol dehydrogenase
      reaction.

PMID- 8138544
TI  - Membrane-intercalated proteoglycan of a stroma-inducing clone from Lewis lung
      carcinoma binds to fibronectin via its heparan sulfate chains.
AB  - A Lewis lung carcinoma-derived low metastatic clone, P29, with a capacity to
      induce a fibrotic stromal response of host tissue, exhibits tumorigenesis
      depending on an interstitial matrix formed by the induced stromal cells. Using
      this clone, in the present study we isolated and characterized a membrane
      intercalated proteoglycan that mediates interaction between the tumor cells and
      interstitial matrix. The tumor cells were cultured in the presence of
      [3H]glucosamine and [35S]sulfate or [35S]methionine, and hydrophobic
      proteoglycans were isolated by chromatography on DEAE-Sephacel and then Octyl
      Sepharose CL-4B. Proteoglycans with high affinity to the octylresidue were
      obtained from the cell layer but not to any significant extent from the medium.
      By CsCl density gradient centrifugation, they were separated into bottom, middle,
      and top subfractions, which were shown to consist of homogeneous species with
      estimated M(r) values of 270,000 (named CPGIIIB), 200,000 (CPGIIIM), and 195,000
      (CPGIIIT), respectively, by gel filtration on Sepharose CL-4B. These
      proteoglycans were intercalated into phosphatidylcholine liposomes, suggesting
      that they are all membrane-intercalated proteoglycans. Analyses of their
      glycosaminoglycans with chondroitinase ABC and heparitinase I plus II
      demonstrated that they all contain heparan sulfate as a major glycosaminoglycan
      (58-85%) and chondroitin 4-sulfate as a minor one (15-42%). Of these three
      proteoglycans, only CPGIIIB proteoglycan bound specifically to fibronectin
      Sepharose 4B under physiological conditions. Molecular analyses of this
      proteoglycan by Sepharose CL-4B or SDS-PAGE before and after treatments with
      glycosaminoglycan degradation enzymes or trifluoromethanesulfonic acid
      demonstrated that CPGIIIB proteoglycan is a hybrid proteoglycan having heparan
      sulfate and chondroitin 4-sulfate chains on the same core protein with an M(r) of
      40,000. Affinity chromatographies of the CPGIIIB proteoglycan on fibronectin
      Sepharose 4B after treatments with these enzymes demonstrated that it bound to
      fibronectin via its heparan sulfate chains. On the basis of the above results, we
      propose that the CPGIIIB proteoglycan mediates the interaction between the tumor
      cells and interstitial matrix.

PMID- 8138545
TI  - Increases in protein phosphatase 2B activity in lymphoid tissues and T
      lymphocytes of autoimmune MRL/MpJ-lpr/lpr mice.
AB  - The assay conditions for protein phosphatase 2B (PP2B) in crude extracts from
      mouse lymphoid tissues and lymphocytes were extensively investigated. Under the
      conditions elucidated, the PP2B activity was measured in autoimmune-prone MRL/MpJ
      lpr/lpr mice (MRL/lpr mice) and two control strains, MRL/MpJ- +/+ mice (MRL/+/+
      mice) and C3H/HeJ mice. In the control mice, PP2B activity was distinctly higher
      in spleen and thymus than brain and liver. PP2B activity was further elevated in
      spleen of MRL/lpr mice than in the controls. Furthermore, we observed a specific
      increase in PP2B activity in T lymphocytes from MRL/lpr mice as compared with in
      those from control mice. On the other hand, no alteration was observed in PP2B
      activity in B lymphocytes. These results suggest the involvement of PP2B in the
      abnormal signal transduction and proliferation of T lymphocytes in MRL/lpr mice.

PMID- 8138546
TI  - Characterization of the electron acceptors of old yellow enzyme: mechanistic
      approach to the mode of one electron transfer from the enzyme to menadione or
      dyestuffs.
AB  - Molecular oxygen or cytochrome c has been described as the electron acceptor of
      the reaction of old yellow enzyme with NADPH. In this study, menadione was found
      to be a sensitive electron acceptor of the reaction under aerobic as well as
      anaerobic conditions. The Km value of menadione for old yellow enzyme is as low
      as 2-3 x 10(-7) M in the presence or absence of superoxide dismutase. The rate
      enhancement of the cytochrome c reduction of old yellow enzyme with NADPH was
      about eight times in the presence of menadione. The rate increment was slightly
      higher under aerobic than anaerobic conditions. The rate enhancement by menadione
      enabled sensitive determination of the enzyme activity in the assay system, which
      contained NADPH, cytochrome c, menadione, and old yellow enzyme. In the reaction
      course, the semiquinone species of menadione was trapped by the reaction with t
      butyl-alpha-phenylnitrone. The radical adduct was detected on EPR. The dyestuff,
      2,6-dichlorophenolindophenol, was found to be reduced ineffectively even in the
      presence of menadione; moreover, it was inhibitory in the NADPH consumption
      reaction. Methylene blue or Lauth's violet, known to be capable of semiquinone
      formation, also behaved, like menadione, as a mediator of electron transport to
      cytochrome c. On the basis of the experimental results, the occurrence of the one
      electron transfer of the old yellow enzyme reaction was emphasized.

PMID- 8138547
TI  - Immunological application of the dihydrofolate reductase handle carrying a small
      peptide, leucine enkephalin.
AB  - The "dihydrofolate reductase (DHFR) handle" [Iwakura, M. et al. (1992) J.
      Biochem. 111, 37-45; Iwakura, M. & Tanaka, T. (1992) J. Biochem. 111, 638-642]
      fused with a pentapeptide, leucine enkephalin (LEK), has been applied in
      immunoassays for LEK and for the preparation of anti-LEK monoclonal antibody.
      DHFR fused with LEK (DHFR-LEK) was first utilized as an immobilized antigen in an
      enzyme-linked immunosorbent assay for LEK. By using a commercially available anti
      LEK and peroxidase-linked anti-IgG, LEK could be quantified in the range between
      0.1 ng/ml and 10 micrograms/ml. By using a commercially available anti-LEK and
      the DHFR-LEK as an enzyme-labeled antigen, LEK was quantified in the range
      between 0.1 ng/ml and 1 microgram/ml by monitoring the recovery of the DHFR
      activity from the immuno-precipitates. By using the DHFR-LEK as an immunogen,
      three mouse monoclonal antibodies against LEK, but not DHFR, were isolated. All
      three monoclonal antibodies were of IgG1 kappa type. The large-scale preparation
      of two of these monoclonal antibodies, designated as anti-LEK-36 and anti-LEK-74,
      was carried out and their recognition specificities were studied by competitive
      binding assays. The IC50 values of LEK for the anti-LEK-36 and anti-LEK-74 were
      3.74 x 10(-6) and 4.66 x 10(-6) M, respectively. The competitive binding assays
      showed that recognition specificities of the two monoclonal antibodies were high
      and restricted to LEK and leucine-enkephalin (sulfated form). These results
      strongly suggest that the DHFR handle is useful in several immunological
      applications.

PMID- 8138548
TI  - Most bovine milk fat globule membrane glycoproteins contain asparagine-linked
      sugar chains with GalNAc beta 1-->4GlcNAc groups.
AB  - N-Acetylgalactosamine is usually not a constitutive monosaccharide of Asn-linked
      sugar chains. Our previous study showed that the Asn-linked sugar chains of
      bovine CD36 prepared from milk fat globule membranes (MFGM) contain this unique
      monosaccharide as the GalNAc beta 1-->4GlcNAc group [Nakata et al. (1993)
      Biochemistry 32, 4369-4383]. Western blot analysis of bovine MFGM glycoproteins
      with Wistaria floribunda agglutinin (WFA), which binds oligosaccharides
      terminating with either an alpha- or beta-N-acetylgalactosamine residue, showed
      that WFA binding is observed for most of the protein bands as detected with
      Coomassie Brilliant Blue staining. However, no WFA binding was observed for
      protein bands after treatment of MFGM glycoproteins with N-glycanase. Structural
      analyses of the sugar chains released by hydrazinolysis from the MFGM
      glycoproteins by sequential exoglycosidase digestion and by methylation analysis
      revealed that oligosaccharides, which bound to a WFA-agarose column, are bi-, tri
      , and tetraantennary complex-type and hybrid-type sugar chains with the GalNAc
      beta 1-->4GlcNAc group in their outer chain moieties, while oligosaccharides,
      which passed through the column, were of high-mannose-type, hybrid-type, and
      complex-type, of which the latter two groups contained the Gal beta 1-->4GlcNAc
      groups. These results indicated that many bovine MFGM glycoproteins contain Asn
      linked sugar chains with the GalNAc beta 1-->4GlcNAc group.

PMID- 8138549
TI  - Activation of human lysosomal sialidase.
AB  - An acid sialidase [EC 3.2.1.18], partially purified from human placenta by Con A
      Sepharose adsorption and p-aminophenyl thio-beta-D-galactoside-CH-Sepharose (PATG
      Sepharose) affinity chromatographies, was activated by incubation at 37 degrees
      C. This activation showed both time and temperature dependencies, with the most
      effective activation observed at 37 degrees C in the pH range between 4.3 and
      5.2. The influence of various protease inhibitors on its activation was
      investigated. Among the protease inhibitors tested, amastatin, an inhibitor of
      aminopeptidase A, significantly inhibited activation. The partially purified
      enzyme preparation contained aminopeptidase activity, which was inhibited by
      amastatin. Zinc ions inhibited either the activation of sialidase or the
      aminopeptidase activity in the enzyme preparation. These results suggest the
      possibility of participation of aminopeptidase function in the activation process
      of sialidase.

PMID- 8138550
TI  - Identification of amino acid residues responsible for the changes of absorption
      and fluorescence spectra on the binding of subtilisin BPN' and Streptomyces
      subtilisin inhibitor.
AB  - An ultraviolet absorption difference spectrum characteristic of the ionization
      change of a tyrosyl residue was observed on the binding of subtilisin BPN' with
      Streptomyces subtilisin inhibitor (SSI) at alkaline pH. This difference spectrum
      was considered to be induced by a pKa shift (from 9.7 to > or = 11.5) of a
      tyrosyl residue of subtilisin BPN' in the interaction with carboxyls of SSI
      [Inouye et al. (1979) J. Biochem. 85, 1115-1126]. In the present paper, the
      tyrosyl residue in subtilisin BPN' and the carboxyls in SSI were identified by
      analyzing the difference spectrum using mutants of subtilisin BPN' and SSI:
      naturally occurring mutants and those prepared by site-directed and cassette
      mutagenesis. The difference spectrum disappeared on the binding of a mutant
      subtilisin BPN' of which Tyr104 was replaced by Phe (S-BPN'Y104F) and SSI at pH
      9.8. The magnitude of the absorption difference was much smaller when subtilisin
      BPN' was bound with a mutant SSI of which both Glu67 and Asp68 were replaced by
      Gly than with the wild-type SSI. These lines of evidence indicated that the
      difference spectrum was caused by Tyr104 of subtilisin BPN' interacting with
      Glu67 and Asp68 of SSI. The binding of subtilisin BPN' and SSI is accompanied by
      an increase of tryptophan fluorescence, which is pH-dependent in the range of pH
      7-11 [Uehara et al. (1978) J. Biochem. 84, 1195-1202]. In the present study, this
      pH-dependence of the fluorescence diminished when SSI bound with S-BPN'Y104F.
      This suggested that the fluorescence increase was due to Trp106 of subtilisin
      BPN' and was influenced by the ionization of Tyr104.

PMID- 8138551
TI  - 3-Cyano-2,6-dihydroxypyridine (CNDP), a new potent inhibitor of dihydrouracil
      dehydrogenase.
AB  - 3-Cyano-2,6-dihydroxypyridine (CNDP) was identified as a potent inhibitor (IC50
      value, 4.4 nM) of dihydrouracil dehydrogenase (DHUDase) [EC 1.3.1.2], a rate
      limiting enzyme in 5-fluorouracil (5-FU) degradation. The inhibitory activity of
      CNDP was about 2,000 times that of uracil under our assay conditions. Kinetic
      analyses with partially purified enzyme from rat liver revealed that the
      mechanism of inhibition of DHUDase by CNDP was of mixed type with an inhibition
      constant (Ki) of 1.51 nM. CNDP had less effect on 5-FU phosphorylation than on 5
      FU degradation. The inhibitory effect of CNDP on ribosylation of 5-FU was 600 to
      1,000 times less than that on DHUDase. Moreover, CNDP did not inhibit uridine
      kinase, thymidine kinase, or pyrimidine phosphoribosyltransferase.
      Coadministration of CNDP with 1-ethoxymethyl-5-fluorouracil (EM-FU) to rats with
      Yoshida sarcoma elevated the level of 5-FU in both the blood and the tumor and
      enhanced the antitumor effect of EM-FU. These findings indicated that CNDP would
      be a useful chemical modulator in chemotherapy with 5-FU or its prodrugs.

PMID- 8138552
TI  - Acidic regions of cytochrome c1 are essential for ubiquinol-cytochrome c
      reductase activity in yeast cells lacking the acidic QCR6 protein.
AB  - It has been suggested that the two acidic regions around residue 70 and residue
      170 in yeast cytochrome c1, a subunit of ubiquinol-cytochrome c reductase
      (complex III), interact with cytochrome c in the electron transfer reaction and
      that the QCR6 protein, the acidic subunit of yeast complex III, enhances this
      interaction. In order to determine the roles of the acidic regions of cytochrome
      c1 more precisely, we introduced several mutations in the two acidic regions and
      examined their effects on the ability of modified cytochrome c1 to complement the
      respiration deficiency of yeast cells lacking only cytochrome c1 or both
      cytochrome c1 and the QCR6 protein. The mutant cytochrome c1 with the deletion of
      the first acidic region (delta 68-80) was still functional in the cytochrome c1
      deficient strain. Mutant cytochrome c1 with the deletion of the second acidic
      region (delta 168-179) caused a decrease in the complementing ability, but this
      is probably due to failure in its proteolytic maturation and/or correct assembly
      into complex III. Mutant cytochrome c1 with altered charge distribution in the
      acidic regions (Asp170Asp171-->Asn170Asn171 or Asp170Asp171-->Asn170Lys171) made
      the cytochrome c1-deficient cells respiration-competent. On the other hand,
      mutant cytochrome c1 with the deletion of the first acidic region (delta 68-80)
      or altered charge distribution in the second region (Asp170Asp171-->Asn170Lys171)
      did not restore the respiration deficiency of the cells lacking not only
      cytochrome c1 but also the QCR6 protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138553
TI  - RecA protein from an extremely thermophilic bacterium, Thermus thermophilus HB8.
AB  - The recA gene of a thermophilic eubacterial strain, Thermus thermophilus (T.th.)
      HB8, was cloned from a genomic DNA library by Southern hybridization using a gene
      internal fragment amplified by the polymerase chain reaction (PCR) method as the
      probe. The gene encoded a 36 kDa polypeptide whose amino acid sequence showed 61%
      identity with that of the Escherichia coli RecA protein. Characteristic amino
      acid changes between the two RecA proteins were found. In the amino acid
      composition of the T.th. RecA protein, the number of Pro residues was increased,
      the number of Cys residues was decreased, and Lys residues were replaced by Arg,
      Asp by Glu, Thr by Val, and Ile by Val or Leu. These changes are supposed to
      stabilize the native protein conformation against heat denaturation. The amino
      acid residues in the nucleotide binding site of the protein and in the protein
      protein interaction site responsible for the oligomer formation were well
      conserved. The T.th. recA gene has the ability to complement the ultraviolet
      light (UV) sensitivity of a E. coli recA deletion mutant. Thus, the thermophilic
      bacterium has a RecA protein whose function will be common to the E. coli RecA
      protein.

PMID- 8138554
TI  - An inducible NADP(+)-dependent D-phenylserine dehydrogenase from Pseudomonas
      syringae NK-15: purification and biochemical characterization.
AB  - An inducible NADP(+)-dependent D-phenylserine dehydrogenase [EC 1.1.1.-], which
      catalyzes the oxidation of the hydroxyl group of D-threo-beta-phenylserine, was
      purified to homogeneity from a crude extract of Pseudomonas syringae NK-15
      isolated from soil. The enzyme consisted of two subunits identical in molecular
      weight (about 31,000). In addition to D-threo-beta-phenylserine, it utilized D
      threo-beta-thienylserine, D-threo-beta-hydroxynorvaline, and D-threonine as
      substrates but was inert towards other isomers of beta-phenylserine and
      threonine. It showed maximal activity at pH 10.4 for the oxidation of D-threo
      beta-phenylserine, and it required NADP+ as a natural coenzyme. NAD+ showed a
      slight coenzyme activity. The enzyme was inhibited by p-chloromercuribenzoate,
      HgCl2, and monoiodoacetate but not by the organic acids such as tartronate. The
      Michaelis constants for D-threo-beta-phenylserine and NADP+ were 0.44 mM and 29
      microM, respectively. The N-terminal 27 amino acids sequence was determined. It
      suggested that the NADP(+)-binding site was located in the N-terminal region of
      the enzyme.

PMID- 8138555
TI  - Distribution of dystrophin isoforms and dystrophin-associated proteins 43DAG
      (A3a) and 50DAG (A2) in various monkey tissues.
AB  - To determine the distributions of two known dystrophin isoforms derived from the
      3' part of the dystrophin gene and of the dystrophin-associated proteins [50DAG
      (A2) and 43DAG (A3a)] by immunoblot analysis, we examined various monkey tissues
      [skeletal (quadriceps), cardiac (left ventricle), and smooth (aorta and uterus)
      muscles, lung, liver, central nervous system (cerebrum, cerebellum, and spinal
      cord), and peripheral nerve (sciatic nerve)]. With the antibody against the C
      terminal domain of dystrophin, we found three bands other than the 400-kDa band
      corresponding to dystrophin or utrophin. These are a 130-kDa band detected in
      central nervous system, a 110-kDa band in peripheral nerve and spinal cord, and a
      70-kDa band in all the tissues examined except skeletal muscle and peripheral
      nerve. The 130-kDa band may be a novel protein not yet reported, while the last
      two bands may correspond to Dp116 and Dp71, respectively [Lederfein et al. (1992)
      Proc. Natl. Acad. Sci. USA 89, 5346-5350 and Byers et al. (1993) Nature Genet. 4,
      77-81]. Dystrophin-associated protein, 43DAG, was detected in all the tissues
      examined, but 50DAG was detected only in skeletal and cardiac muscles.
      Furthermore, a unique 70-kDa band reacting with anti-50DAG antiserum was found in
      all the tissues other than skeletal muscle.

PMID- 8138556
TI  - Promotional effects of azathioprine on peripheral B cell lymphomas in BALB/c mice
      induced by administration of 7,12-dimethylbenz[a]anthracene.
AB  - BALB/c mice either were injected subcutaneously with 25 micrograms/g or 50
      micrograms/g body weight 7,12-dimethyl-benz[a]anthracene (DMBA) at the age of 13
      weeks, or received repeated s.c. injections of azathioprine (0.1 mg/g) starting
      from the age of 6 or 18 weeks, or they received treatments with both agents. Of
      the 317 mice treated, 69 developed lymphomas by the age of 50 weeks. None of the
      31 non-treated mice developed lymphomas during this period. The lymphomas,
      classified according to Pattengale-Taylor's classification for murine
      lymphomas/leukemias, were examined immunohistochemically and immunogenetically.
      The lymphomas induced with DMBA showed a male preponderance and a higher
      incidence of the B cell type, especially in the lymph node and spleen.
      Azathioprine induced predominantly T-lymphoblastic lymphomas in the thymus and
      these were found more frequently in females. Treatment with both DMBA and
      azathioprine remarkably increased the incidence of B lymphomas, especially
      follicular center cell lymphomas in the spleen, which are the predominant type of
      spontaneous lymphomas occurring in older BALB/c mice. Some of the treated mice
      also developed prelymphomatous lesions.

PMID- 8138557
TI  - Expression of sialosyl-Tn antigen (monoclonal antibody MLS102 reactive) in normal
      tissues and malignant tumors of the digestive tract.
AB  - Oncogenic transformation is often associated with changes in the glycosylation
      state of malignant cells. We investigated the immunohistochemical localization of
      sialosyl-Tn antigen [O-linked NeuAc(alpha 2-->6)GAINAc] using a novel monoclonal
      antibody MLS102 in normal and malignant digestive-tract tissues. In normal
      tissues, weak MLS102 immunoreactivity was observed in the epithelium of the
      esophagus, stomach and colon. However, MLS102 immunoreactivity was strong in the
      goblet cells of the duodenum, but not in the Brunner glands. In carcinomas of the
      esophagus, stomach, colon, pancreas and biliary tract, positive staining was
      detected with a high frequency (80%-100%). In mucinous carcinomas and signet-ring
      cell carcinomas, malignant cells themselves and the mucins they secreted were
      strongly positive for sialosyl-Tn antigen. There was no significant correlation
      between the frequency of expression of sialosyl-Tn antigen and the degree of
      differentiation (grade). However, in the case of well-differentiated
      adenocarcinomas, sialosyl-Tn antigen was found mainly in the supranuclear areas
      (Golgi area), on the apical surface and in the adjacent cytoplasm. In poorly
      differentiated adenocarcinomas, the antigen was often detected in the whole
      plasma membrane and cytoplasm. Therefore, monoclonal antibody MLS102 may be
      useful in further elucidating the characteristics of digestive-tract cancers, and
      possibly in their treatment.

PMID- 8138558
TI  - Mesothelioma-like tumors of the pleura: a review of 72 autopsy cases.
AB  - The 72 mesothelioma-like tumors of the pleura (MLTP) found among 33 500 autopsy
      cases collected over more than 30 years are reviewed. MLTP have a worse prognosis
      than the 106 cases of pleural mesothelioma autopsied in our institutes with
      regard to survival time and metastatic spread. In MLTP, adenocarcinomas
      predominate with a wide range of histological and cytological variation and
      prominent development of connective tissue having its origin in the periphery of
      the lung. These intrapulmonary primary tumors often fulfill the criteria of
      pulmonary scar cancer. Etiologically, there is no correlation between the origin
      of this tumor and smoking or exposure to asbestos. The absence of mucus formation
      and glandular differentiation, together with the presence of spindle-shaped
      carcinoma components and strong mesothelial or stroma proliferation, can make the
      differential diagnosis between this tumor type and mesothelioma difficult.
      Immunohistological investigations were performed on 11 cases with antibodies
      against intermediate filament proteins, vascular endothelium, collagen IV,
      macrophage antigens, carcinoembryonic antigen (CEA), LeuM1, and the antibody
      BerEP4. Our investigation shows that a battery of several tumor markers, such as
      antibodies against LeuM1, CEA, and the antibody BerEP4, as well as staining with
      periodic acid/Schiff/diastase discriminate primary from secondary pleural
      neoplasms, whilst intermediate filament proteins alone are of little diagnostic
      value.

PMID- 8138559
TI  - Pulmonary alveolar proteinosis in rats after administration of quartz: its
      possible role in morphogenesis of lung cancer.
AB  - In rats, primary peripheral lung tumors composed predominantly of alveolar type
      II cells have been induced by inhalation of alpha quartz. In our retrospective
      study on proliferation markers we evaluated lung specimens of 140 Wistar rats
      from larger experiments, which had been exposed to Dorentrup quartz (DQ12) by
      inhalation (10 mg/m3, 56 Weeks, 5 days/week, 7 h/day: n = 27) or intratracheal
      instillations (5 mg: n = 38; 20 mg: n = 10; 50 mg: n = 28; 15 x 3 mg: n = 12). In
      the last group 8/12 animals developed lung tumors. Animals were sacrificed 1-32
      months after administration. For identification of an increased proliferation of
      alveolar type II cells the DNA content was monitored by microscopic (static)
      cytophotometry in histological slides. The argyrophil (AgNOR) method for the
      demonstration of nucleolar organizer regions (NOR) was used as second marker of
      type II cell proliferation. Measurements made 24 months after inhalation of DQ12
      showed a slight increase of pneumocytic proliferation with 1.64 +/- 0.14
      AgNOR/nucleus compared to the controls (1.23 +/- 0.04 mean AgNOR/nucleus). After
      intratracheal instillation of DQ12 a significant increase of AgNOR was found,
      e.g. 5 mg: 1.93 +/- 0.23 AgNOR/nucleus (6 months) and 1.96 +/- 0.19 (12 months);
      50 mg: 1.77 +/- 15 (6 months) and 2.18 +/- 0.05 (12 months); 15 x 3 mg (+2 ml 2%
      polyvinylpyridine N-oxide s.c.): 1.81 +/- 0.13 AgNOR/nucleus (27-32 months). With
      the aid of the 2 c deviation index, i.e. the mean square deviation from the
      diploid DNA value, it was possible also to identify the pathologically increased
      proliferation of type II cells after intratracheal instillation of quartz: 0.02
      +/- 0.01-0.06 +/- 0.04 c2 (controls); 0.07 +/- 0.04 c2 (5 mg/12 months); 0.12 +/-
      0.08 c2 (15 x 3 mg/>27 months) and 0.68 +/- 0.48 c2 (50 mg/12 months). Only in
      the last group were nearly triploid values detected. Summarizing our results,
      intratracheal instillation and inhalation of quartz in rats regularly induces
      alveolar proteinosis and interstitial fibrosis in combination with a dose- and
      time-dependent increase of the type II cell proliferation rate. As mitogenesis
      increases carcinogenesis, alveolar proteinosis with increased pneumocytic
      proliferative activity might be a prerequisite for enhanced tumor development.

PMID- 8138560
TI  - Inhibition of protein-kinase-C--dependent cell proliferation of human lung cancer
      cell lines by the dihydropyridine dexniguldipine.
AB  - The dihydropyridine, dexniguldipine hydrochloride (B859-35), has shown
      therapeutic activity in experimentally induced neuroendocrine hamster lung tumors
      and demonstrated antiproliferative effects in a mammary cancer cell line via
      inhibition of Ca2+ calmodulin. Studies in NIH 3T3 fibroblasts have provided
      evidence that dexniguldipine may also inhibit protein kinase C (PKC). In this
      study, we have tested the hypothesis that dexniguldipine may inhibit the
      proliferation of lung cancer cells in response to autocrine or exogenous
      activation of PKC. Using a panel of human lung cancer cell lines, we show that
      dexniguldipine is a potent inhibitor of mitogenic signal transduction pathways
      dependent on PKC activation in several small-cell and non-small-cell lung cancer
      cell lines while it failed to inhibit cyclic-AMP-dependent cell proliferation.

PMID- 8138561
TI  - A rapid luciferase transfection assay for transcription activation effects and
      stability control of estrogenic drugs in cell cultures.
AB  - A rapid assay system for measuring the potential of estrogenic drugs is
      introduced. Luciferase induction could be measured in estrogen-receptor-positive
      human MCF-7 breast cancer cells, which had been transfected with a novel
      luciferase reporter plasmid ERE luc. The minimal requirement was 1 h exposure to
      the inducing drug and 3.5 h of incubation after removal of the drug. The assay
      system was used to measure the stability of the drug diaqua-[1,2-bis (2,6
      dichloro-4-hydroxyphenyl) ethylenediamine] platinum(II) sulfate, containing an
      estrogenic ligand and reactive platinum. Luciferase activity was observed only
      when the drug was in the culture medium and cells for short times, whereas the
      estrogenic ligand alone remained active. It is assumed that binding of the
      platinum moiety to macromolecular constituents of the culture or cells renders
      the drug inaccessible for binding to the estrogen receptor.

PMID- 8138562
TI  - An application of MIB antibody to the retrospective study of melanomas of oral
      mucosa and facial skin.
AB  - A new monoclonal antibody prepared against a fragment of Ki-67 antigen MIB, from
      Dianova, was applied for investigation of malignant melanomas of facial skin (25
      cases) and the oral cavity (25 cases), which were routinely embedded in paraffin.
      The values of the Ki-67 index (expressed as a percentage of positive nuclei) were
      correlated with TNM characteristics of tumors and patient survival. Significant
      correlation was found between the Ki-67 index and the level of lymph node
      involvement (N value), the presence of distant metastases and the time of patient
      survival. A positive relationship between the Ki-67 value and tumor size was also
      observed although it lacked statistical significance.

PMID- 8138563
TI  - Antioxidant enzyme activities and oxidative stress in human breast cancer.
AB  - We have analysed products of lipid peroxidation reactions and activities of
      antioxidant enzymes in cancerous breast tissue and in corresponding reference
      tissue. In addition, the serum lipid peroxidation and peroxyl-radical-trapping
      capacity of breast cancer patients were compared to those of healthy subjects. A
      total of 23 patients with breast cancer participated in this study. In the
      cancerous tissue, catalase activity was lower than in the reference tissue, while
      the activities of superoxide dismutase, glutathione peroxidase and the hexose
      monophosphate shunt were elevated. The content of thiobarbituric-acid-reactive
      material was slightly lower in the cancerous tissues, but the levels in serum
      were found to be elevated in patients with breast cancer. The amounts of
      conjugated diene double bonds were essentially equal both in the cancerous and in
      the reference tissue. Moreover, in breast cancer patients the serum levels of
      diene conjugation and the peroxyl-radical-scavenging capacity did not differ from
      those measured in healthy subjects. This study indicates that the antioxidant
      defence system is altered in cancerous breast tissues, but does not support the
      hypothesis suggesting that formation of lipid peroxides in the tumour tissue
      itself is of primary importance in the carcinogenesis.

PMID- 8138564
TI  - The three-dimensional architecture of chromatin in situ: electron tomography
      reveals fibers composed of a continuously variable zig-zag nucleosomal ribbon.
AB  - The three dimensional (3D) structure of chromatin fibers in sections of nuclei
      has been determined using electron tomography. Low temperature embedding and
      nucleic acid-specific staining allowed individual nucleosomes to be clearly seen,
      and the tomographic data collection parameters provided a reconstruction
      resolution of 2.5 nm. Chromatin fibers have complex 3D trajectories, with
      smoothly bending regions interspersed with abrupt changes in direction, and U
      turns. Nucleosomes are located predominantly at the fiber periphery, and linker
      DNA tends to project toward the fiber interior. Within the fibers, a unifying
      structural motif is a two nucleosome-wide ribbon that is variably bent and
      twisted, and in which there is little face-to-face contact between nucleosomes.
      It is suggested that this asymmetric 3D zig-zag of nucleosomes and linker DNA
      represents a basic principle of chromatin folding that is determined by the
      properties of the nucleosome-linker unit. This concept of chromatin fiber
      architecture is contrasted with helical models in which specific nucleosome
      nucleosome contacts play a major role in generating a symmetrical higher order
      structure. The transcriptional control implications of a more open and irregular
      chromatin structure are discussed.

PMID- 8138565
TI  - Chromatin fibers observed in situ in frozen hydrated sections. Native fiber
      diameter is not correlated with nucleosome repeat length.
AB  - Chromatin fibers have been observed and measured in frozen hydrated sections of
      three types of cell (chicken erythrocytes and sperm of Patiria miniata and Thyone
      briareus) representing an approximately 20-bp range of nucleosomal repeat
      lengths. For sperm of the starfish P. miniata, it was possible to obtain images
      of chromatin fibers from cells that were swimming in seawater up to the moment of
      cryo-immobilization, thus providing a record of the native morphology of the
      chromatin of these cells. Glutaraldehyde fixation produced no significant changes
      in the ultrastructure or diameter of chromatin fibers, and fiber diameters
      observed in cryosections were similar to those recorded after low temperature
      embedding in Lowicryl K11M. Chromatin fiber diameters measured from cryosections
      of the three types of nuclei were similar, a striking contrast to the situation
      for chromatin isolated from these cell types, where a strong positive correlation
      between diameter and nucleosomal repeat length has been established. The
      demonstration of chromatin fibers in unfixed whole cells establishes an
      unequivocal baseline for the study of native chromatin and chromosome
      architecture. The significant differences between chromatin fibers in nucleo and
      after isolation supports a previous observation (P. J. Giannasca, R. A. Horowitz,
      and C. L. Woodcock. 1993. J. Cell Sci. 105:551-561), and suggests that structural
      studies on isolated material should be interpreted with caution until the changes
      that accompany chromatin isolation are understood.

PMID- 8138566
TI  - A phosphatidylinositol/phosphatidylcholine transfer protein is required for
      differentiation of the dimorphic yeast Yarrowia lipolytica from the yeast to the
      mycelial form.
AB  - The SEC14SC gene encodes the phosphatidylinositol/phosphatidylcholine transfer
      protein (PI/PC-TP) of Saccharomyces cerevisiae. The SEC14SC gene product
      (SEC14pSC) is associated with the Golgi complex as a peripheral membrane protein
      and plays an essential role in stimulating Golgi secretory function. We report
      the characterization of SEC14YL, the structural gene for the PI/PC-TP of the
      dimorphic yeast Yarrowia lipolytica. SEC14YL encodes a primary translation
      product (SEC14YL) that is predicted to be a 497-residue polypeptide of which the
      amino-terminal 300 residues are highly homologous to the entire SEC14pSC, and the
      carboxyl-terminal 197 residues define a dispensible domain that is not homologous
      to any known protein. In a manner analogous to the case for SEC14pSC, SEC14pYL
      localizes to punctate cytoplasmic structures in Y. lipolytica that likely
      represent Golgi bodies. However, SEC14pYL is neither required for the viability
      of Y. lipolytica nor is it required for secretory pathway function in this
      organism. This nonessentiality of SEC14pYL for growth and secretion is probably
      not the consequence of a second PI/PC-TP activity in Y. lipolytica as cell-free
      lysates prepared from delta sec14YL strains are devoid of measurable PI/PC-TP
      activity in vitro. Phenotypic analyses demonstrate that SEC14pYL dysfunction
      results in the inability of Y. lipolytica to undergo the characteristic dimorphic
      transition from the yeast to the mycelial form that typifies this species.
      Rather, delta sec14YL mutants form aberrant pseudomycelial structures as cells
      enter stationary growth phase. The collective data indicate a role for SEC14pYL
      in promoting the differentiation of Y. lipolytica cells from yeast to mycelia,
      and demonstrate that PI/PC-TP function is utilized in diverse ways by different
      organisms.

PMID- 8138567
TI  - The JNM1 gene in the yeast Saccharomyces cerevisiae is required for nuclear
      migration and spindle orientation during the mitotic cell cycle.
AB  - JNM1, a novel gene on chromosome XIII in the yeast Saccharomyces cerevisiae, is
      required for proper nuclear migration. jnm1 null mutants have a temperature
      dependent defect in nuclear migration and an accompanying alteration in astral
      microtubules. At 30 degrees C, a significant proportion of the mitotic spindles
      is not properly located at the neck between the mother cell and the bud. This
      defect is more severe at low temperature. At 11 degrees C, 60% of the cells
      accumulate with large buds, most of which have two DAPI staining regions in the
      mother cell. Although mitosis is delayed and nuclear migration is defective in
      jnm1 mutant, we rarely observe more than two nuclei in a cell, nor do we
      frequently observe anuclear cells. No loss of viability is observed at 11 degrees
      C and cells continue to grow exponentially with increased doubling time. At low
      temperature the large budded cells of jnm1 mutants exhibit extremely long astral
      microtubules that often wind around the periphery of the cell. jnm1 mutants are
      not defective in chromosome segregation during mitosis, as assayed by the rate of
      chromosome loss, or nuclear migration during conjugation, as assayed by the rate
      of mating and cytoduction. The phenotype of a jnm1 mutant is strikingly similar
      to that for mutants in the dynein heavy chain gene (Eshel, D., L. A. Urrestarazu,
      S. Vissers, J.-C. Jauniaux, J. C. van Vliet-Reedijk, R. J. Plants, and I. R.
      Gibbons. 1993. Proc. Natl. Acad. Sci. USA. 90:11172-11176; Li, Y. Y., E. Yeh, T.
      Hays, and K. Bloom. 1993. Proc. Natl. Acad. Sci. USA. 90:10096-10100). The JNM1
      gene product is predicted to encode a 44-kD protein containing three coiled coil
      domains. A JNM1:lacZ gene fusion is able to complement the cold sensitivity and
      microtubule phenotype of a jnm1 deletion strain. This hybrid protein localizes to
      a single spot in the cell, most often near the spindle pole body in unbudded
      cells and in the bud in large budded cells. Together these results point to a
      specific role for Jnm1p in spindle migration, possibly as a subunit or accessory
      protein for yeast dynein.

PMID- 8138568
TI  - IFAP 300 is common to desmosomes and hemidesmosomes and is a possible linker of
      intermediate filaments to these junctions.
AB  - The distribution of IFAP 300, a protein previously characterized as cross-linking
      vimentin intermediate filaments (IF), has been investigated in epithelial cells.
      In frozen sections of bovine tongue epithelium the staining obtained with IFAP
      300 antibodies is concentrated in the peripheral cytoplasm of keratinocytes,
      including the entire peripheral region of basal cells. Further immunofluorescence
      studies reveal that in primary cultures of mouse keratinocytes the distribution
      of IFAP 300 is similar to that of the desmosomal protein desmoplakin. In rat
      bladder carcinoma 804G cells the staining pattern of IFAP 300 antibodies
      coincides with that obtained with antibodies against the hemidesmosomal protein
      BP 230. By immunogold electron microscopy IFAP 300 is mainly located at sites
      where IF appear to attach to desmosomes and hemidesmosomes. Morphometric analyses
      of the distribution of the gold particles show that IFAP 300 overlaps with
      desmoplakin and BP 230, but also that it extends deeper into the cytoplasm than
      these latter two proteins. The staining reaction seen in epithelial cells by
      immunofluorescence and immunogold is specific for IFAP 300 as shown by
      immunoblotting. Immunoblotting also reveals that IFAP 300 is present in both cell
      free preparations of desmosomes and hemidesmosomes. These morphological and
      biochemical results are intriguing since, in recent years, the proteins appearing
      in these two types of junctions have been found to be different. One possible
      exception is plectin, a protein that has been suggested to be very similar to
      IFAP 300. However, we show here that IFAP 300 differs from plectin in several
      respects, including differences at the primary sequence level. We also show that
      purified IFAP 300 pellets with in vitro polymerized IF prepared from desmosome
      associated keratins under conditions in which IFAP 300 alone is not sedimentable.
      This indicates that IFAP 300 can associate with keratin IF. These data, taken
      together with the immunogold results, suggest that IFAP 300 functions in
      epithelial cells as a linker protein connecting IF to desmosomes as well as to
      hemidesmosomes, possibly through structurally related proteins such as
      desmoplakin and BP 230, respectively.

PMID- 8138569
TI  - Uroplakins Ia and Ib, two major differentiation products of bladder epithelium,
      belong to a family of four transmembrane domain (4TM) proteins.
AB  - The mammalian bladder epithelium elaborates, as a terminal differentiation
      product, a specialized plasma membrane called asymmetric unit membrane (AUM)
      which is believed to play a role in strengthening and stabilizing the urothelial
      apical surface through its interactions with an underlying cytoskeleton. Previous
      studies indicate that the outer leaflet of AUM is composed of crystalline patches
      of 12-nm protein particles, and that bovine AUMs contain three major proteins:
      the 27- to 28-kD uroplakin I, the 15-kD uroplakin II and the 47-kD uroplakin III.
      As a step towards elucidating the AUM structure and function, we have cloned the
      cDNAs of bovine uroplakin I (UPI). Our results established the existence of two
      isoforms of bovine uroplakin I: a 27-kD uroplakin Ia and a 28-kD uroplakin Ib.
      These two glycoproteins are closely related with 39% identity in their amino acid
      sequences. Hydropathy plot revealed that both have four potential transmembrane
      domains (TMDs) with connecting loops of similar length. Proteolytic digestion of
      UPIa inserted in vitro into microsomal vesicles suggested that its two main
      hydrophilic loops are exposed to the luminal space, possibly involved in
      interacting with the luminal domains of other uroplakins to form the 12-nm
      protein particles. The larger loop connecting TMD3 and TMD4 of both UPIa and UPIb
      contains six highly conserved cysteine residues; at least one centrally located
      cysteine doublet in UPIa is involved in forming intramolecular disulfide bridges.
      The sequences of UPIa and UPIb (the latter is almost identical to a hypothetical,
      TGF beta-inducible, TI-1 protein of mink lung epithelial cells) are homologous to
      members of a recently described family all possessing four transmembrane domains
      (the "4TM family"); members of this family include many important leukocyte
      differentiation markers such as CD9, CD37, CD53, and CD63. The tissue-specific
      and differentiation-dependent expression as well as the naturally occurring
      crystalline state of uroplakin I molecules make them uniquely suitable, as
      prototype members of the 4TM family, for studying the structure and function of
      these integral membrane proteins.

PMID- 8138570
TI  - Globular and asymmetric acetylcholinesterase in the synaptic basal lamina of
      skeletal muscle.
AB  - The aim of this study was to characterize the molecular forms of
      acetylcholinesterase (AChE) associated with the synaptic basal lamina at the
      neuromuscular junction. The observations were made on the neuromuscular junctions
      of cutaneous pectoris muscles of frog, Rana pipiens, which are similar to
      junctions of most other vertebrates including mammals, but are especially
      convenient for experimentation. By measuring relative AChE activity in junctional
      and extrajunctional regions of muscles after selective inactivation of
      extracellular AChE with echothiophate, or of intracellular AChE with DFP and 2
      PAM, we found that > 66% of the total AChE activity in the muscle was junction
      specific, and that > 50% of the junction-specific AChE was on the cell surface.
      More than 80% of the cell surface AChE was solubilized in high ionic strength
      detergent-free buffer, indicating that most, if not all, was a component of the
      synaptic basal lamina. Sedimentation analysis of that fraction indicated that
      while asymmetric forms (A12, A8) were abundant, globular forms sedimenting at 4-6
      S (G1 and G2), composed > 50% of the AChE. It was also found that when muscles
      were damaged in various ways that caused degeneration of axons and muscle fibers
      but left intact the basal lamina sheaths, the small globular forms persisted at
      the synaptic site for weeks after phagocytosis of cellular components; under
      certain damage conditions, the proportion of globular to asymmetric forms in the
      vacated basal lamina sheaths was as in normal junctions. While the asymmetric
      forms required high ionic strength for solubilization, the extracellular globular
      AChE could be extracted from the junctional regions of normal and damaged muscles
      by isotonic buffer. Some of the globular AChE appeared to be amphiphilic when
      examined in detergents, suggesting that it may form hydrophobic interactions, but
      most was non-amphiphilic consistent with the possibility that it forms weak
      electrostatic interactions. We conclude that the major form of AChE in frog
      synaptic basal lamina is globular and that its mode of association with the basal
      lamina differs from that of the asymmetric forms.

PMID- 8138571
TI  - Suppression of liver cell apoptosis in vitro by the non-genotoxic
      hepatocarcinogen and peroxisome proliferator nafenopin.
AB  - Suppression of apoptosis has been implicated as a mechanism for the
      hepatocarcinogenicity of the peroxisome proliferator class of non-genotoxic
      carcinogens. The ability of the peroxisome proliferator nafenopin to suppress or
      delay the onset of liver apoptosis was investigated using primary cultures of rat
      hepatocytes and the Reuber hepatoma cell line FaO. 50 microM nafenopin reversibly
      maintained the viability of primary rat hepatocyte cultures which otherwise
      degenerated within 8 d of establishment. The maintenance of viability of
      hepatocyte monolayers was associated with a significant decrease in the number of
      cells exhibiting chromatin condensation patterns typical of apoptosis. Apoptosis
      could be induced in hepatocytes by administration of 5 ng/ml TGF beta 1. Co
      addition of 50 microM nafenopin significantly reduced TGF beta 1-induced
      apoptosis by 50-60%. TGF beta 1 (1-5 ng/ml) also induced apoptosis in the FaO rat
      hepatoma cell line. Cell death was accompanied by detachment of FaO cells from
      the monolayer and detached cells exhibited chromatin condensation and non-random
      DNA fragmentation patterns typical of apoptosis. Co-addition of 50 microM
      nafenopin to TGF beta 1-treated FaO cultures significantly reduced the number of
      apoptotic cells detaching from the monolayer at 24 h. In contrast, nafenopin had
      no significant effect on FaO apoptosis induced by the DNA damaging agents
      etoposide and hydroxyurea. We conclude that suppression of liver cell death by
      apoptosis may play a role in the hepatocarcinogenicity of the peroxisome
      proliferators, although the extent of this protection is dependent on the nature
      of the apoptotic stimulus.

PMID- 8138572
TI  - Kalinin is more efficient than laminin in promoting adhesion of primary
      keratinocytes and some other epithelial cells and has a different requirement for
      integrin receptors.
AB  - Kalinin was purified from squamous cell carcinoma (SCC25) spent culture media
      using an immunoaffinity column prepared from the mAb BM165. The affinity-purified
      material was separated by SDS-PAGE into three bands of 165-155, 140, and 105 kD
      identical to those obtained from normal human keratinocyte cultures and
      previously identified as kalinin. Kalinin promoted adhesion of a large number of
      normal cells and established cell lines with an activity similar to other
      adhesion molecules such as the laminin-nidogen complex, fibronectin, or collagen
      IV. However, kalinin was a much better substrate than laminin-nidogen complex for
      adhesion of cells of epithelial origin including primary human keratinocytes.
      Adhesion to kalinin was followed by cell shape changes ranging from rounded to
      fully spread cells depending on the cell types. The adhesion-promoting activity
      of kalinin was conformation dependent and was abolished by heat denaturation. mAb
      BM165 prevented cell adhesion to kalinin but not to other extracellular matrix
      substrates. However, either complete or partial inhibition was observed with
      different cells suggesting the existence of at least two cell-binding sites on
      the kalinin molecule. Experiments inhibiting cell adhesion with function-blocking
      anti-integrin subunit antibodies indicated that both alpha 3 beta 1 and alpha 6
      beta 1 integrins are involved in the cellular interactions with kalinin, while
      for cell adhesion to classical mouse Engelbreth-Holm-Swarm laminin only alpha 6
      beta 1 integrins, and not alpha 3 beta 1, appeared to be functional. Altogether,
      these results suggest that kalinin may fulfill additional functions than laminin,
      particularly for epithelial cells.

PMID- 8138573
TI  - POM152 is an integral protein of the pore membrane domain of the yeast nuclear
      envelope.
AB  - We have identified a concanavalin A-reactive glycoprotein of 150 kD that
      coenriches with isolated yeast nuclear pore complexes. Molecular cloning and
      sequencing of this protein revealed a single canonical transmembrane segment.
      Epitope tagging and localization by both immunofluorescence and immunoelectron
      microscopy confirmed that it is a pore membrane protein. The protein was termed
      POM152 (for pore membrane protein of 152 kD) on the basis of its location and
      cDNA-deduced molecular mass. POM152 is likely to be a type II membrane protein
      with its NH2-terminal region (175 residues) and its COOH-terminal region (1,142
      residues) positioned on the pore side and cisternal side of the pore membrane,
      respectively. The proposed cisternally exposed domain contains eight repetitive
      motifs of approximately 24 residues. Surprisingly, POM152 deletion mutants were
      viable and their growth rate was indistinguishable from that of wild-type cells
      at temperatures between 17 and 37 degrees C. However, overproduction of POM152
      inhibited cell growth. When expressed in mouse 3T3 cells, POM152 was found to be
      localized to the pore membrane, suggesting a conserved sorting pathway between
      yeast and mammals.

PMID- 8138574
TI  - Human mitochondria and mitochondrial genome function as a single dynamic cellular
      unit.
AB  - rho 0 HeLa cells entirely lacking mitochondrial DNA (mtDNA) and mitochondrial
      transfection techniques were used to examine intermitochondrial interactions
      between mitochondria with and without mtDNA, and also between those with wild
      type (wt) and mutant-type mtDNA in living human cells. First, unambiguous
      evidence was obtained that the DNA-binding dyes ethidium bromide (EtBr) and 4',6
      diamidino-2-phenylindole (DAPI) exclusively stained mitochondria containing mtDNA
      in living human cells. Then, using EtBr or DAPI fluorescence as a probe, mtDNA
      was shown to spread rapidly to all rho 0 HeLa mitochondria when EtBr- or DAPI
      stained HeLa mitochondria were introduced into rho 0 HeLa cells. Moreover,
      coexisting wt-mtDNA and mutant mtDNA with a large deletion (delta-mtDNA) were
      shown to mix homogeneously throughout mitochondria, not to remain segregated by
      use of electron microscopic analysis of cytochrome c oxidase activities of
      individual mitochondria as a probe to identify mitochondria with predominantly wt
      or delta-mtDNA in single cells. This rapid diffusion of mtDNA and the resultant
      homogeneous distribution of the heteroplasmic wt- and delta-mtDNA molecules
      throughout mitochondria in a cell suggest that the mitochondria in living human
      cells have lost their individuality. Thus, the actual number of mitochondria per
      cell is not of crucial importance, and mitochondria in a cell should be
      considered as a virtually single dynamic unit.

PMID- 8138576
TI  - Receptor-mediated transcytosis of IgA in MDCK cells is via apical recycling
      endosomes.
AB  - Classically, the polymeric immunoglobulin receptor and its ligand, IgA, are
      thought to be sorted from basolateral early endosomes into transcytotic vesicles
      that directly fuse with the apical plasma membrane. In contrast, we have found
      that in MDCK cells IgA is delivered from basolateral endosomes to apical
      endosomes and only then to the apical cell surface. When internalized from the
      basolateral surface of MDCK cells IgA is found to accumulate under the apical
      plasma membrane in a compartment that is accessible to two apically added
      membrane markers: anti-secretory component Fab fragments, and avidin internalized
      from the biotinylated apical pole of the cell. This accumulation occurs in the
      presence of apical trypsin, which prevents internalization of the ligand from the
      apical cell surface. Using a modification of the diaminobenzidine density-shift
      assay, we estimate that approximately 80% of basolaterally internalized IgA
      resides in the apical endosomal compartment. In addition, approximately 50% of
      basolaterally internalized transferrin, a basolateral recycling protein, has
      access to this apical endosomal compartment and is efficiently recycled back to
      the basolateral surface. Microtubules are required for the organization of the
      apical endosomal compartment and it is dispersed in nocodazole-treated cells.
      Moreover, this compartment is largely inaccessible to fluid-phase markers added
      to either pole of the cell, and therefore seems analogous to the recycling
      endosome described in nonpolarized cells. We propose a model in which
      transcytosis is not a specialized pathway that uses unique transcytotic vesicles,
      but rather combines portions of pathways used by non-transcytosing molecules.

PMID- 8138575
TI  - Sar1 promotes vesicle budding from the endoplasmic reticulum but not Golgi
      compartments.
AB  - Two new members (Sar1a and Sar1b) of the SAR1 gene family have been identified in
      mammalian cells. Using immunoelectron microscopy, Sar1 was found to be restricted
      to the transitional region where the protein was enriched 20-40-fold in vesicular
      carriers mediating ER to Golgi traffic. Biochemical analysis revealed that Sar1
      was essential for an early step in vesicle budding. A Sar1-specific antibody
      potently inhibited export of vesicular stomatitis virus glycoprotein (VSV-G) from
      the ER in vitro. Consistent with the role of guanine nucleotide exchange in Sar1
      function, a trans-dominant mutant (Sar1a[T39N]) with a preferential affinity for
      GDP also strongly inhibited vesicle budding from the ER. In contrast, Sar1 was
      not found to be required for the transport of VSV-G between sequential Golgi
      compartments, suggesting that components active in formation of vesicular
      carriers mediating ER to Golgi traffic may differ, at least in part, from those
      involved in intra-Golgi transport. The requirement for novel components at
      different stages of the secretory pathway may reflect the recently recognized
      differences in protein transport between the Golgi stacks as opposed to the
      selective sorting and concentration of protein during export from the ER.

PMID- 8138578
TI  - Activation of serpins and their cognate proteases in muscle after crush injury.
AB  - Direct muscle injury was induced in rats in order to evaluate alterations in the
      balance of serine proteases and inhibitors (serpins) as a response to tissue
      damage. It was previously found that certain proteases, specifically urokinase
      like plasminogen activator (uPA) and others, required activation in order to
      effect regeneration. We hypothesized that the magnitude and temporal sequence of
      serpin activation would follow, pari passu, activation of their cognate
      proteases. In addition to uPA, tissue PA (tPA) and tissue kallikrein were the
      proteases studied. The serpins we analyzed were protease nexin I (PNI), PA
      inhibitor 1 (PAI-1, and the kallikrein-binding protein (KBP). uPA nearly doubled
      48 h after injury, while there was no change in amidolytic activity after
      addition of fibrin monomer as an estimation of tPA activity. Tissue kallikrein
      activity, barely detectable in normal muscle, slowly increased, nearly tripling
      at 7 days after injury. Greater magnitude and more rapid changes in muscle
      serpins occurred over the same post-injury time course. By 24 h PNI increased
      threefold, while PAI-1 increased more slowly, reaching double the control values
      by 5 days after injury. Surprisingly, KBP, the serpin-class inhibitor of tissue
      kallikrein, had the most robust response, increasing tenfold over control 48 h
      after crush injury of muscle. These results further implicate the serpin:protease
      balance in tissue injury. Participation of complex receptors, such as the alpha 2
      macroglobulin receptor/low density lipoprotein receptor-related protein (LRP),
      various growth factors, cytokines, and other molecules, in regulating this
      balance is implicated by these data.

PMID- 8138577
TI  - How protein hormones reach their target cells. Receptor-mediated transcytosis of
      hCG through endothelial cells.
AB  - In many organs the vascular endothelium forms a barrier which impedes the free
      diffusion of large molecules. The mechanism by which protein hormones are
      transported through the endothelial cells to reach their target cells is unknown.
      We have examined the transport of human chorionic gonadotropin (hCG) in rat
      testicular microvasculature by electron microscopy and by analysing the transfer
      of radiolabeled hormone and antibodies. Surprisingly, we have observed that the
      same receptor molecule which is present in target Leydig cells is also involved
      in transcytosis through the endothelial cells. The hormone was internalized by
      coated pits and vesicles on the luminal side of the endothelium. It was then
      localized in the endosomal compartment and subsequently appeared to be delivered
      by smooth vesicles into the subendothelial space. Moreover, anti-LH/hCG receptor
      antibodies were efficiently transported via the same system and delivered into
      the interstitial space. If generalized, these observations may define a new level
      of modulation of hormone action and may be of importance for drug targeting into
      the numerous organs which are responsive to the various protein hormones.

PMID- 8138579
TI  - Amphiregulin-dependent proliferation of cultured human keratinocytes: autocrine
      growth, the effects of exogenous recombinant cytokine, and apparent requirement
      for heparin-like glycosaminoglycans.
AB  - Amphiregulin, a member of the epidermal growth factor family with heparin binding
      affinity, functions as a natural regulator of keratinocyte growth. Autocrine
      signaling by amphiregulin and the effects of exogenous recombinant cytokine were
      studied in serum-free cultures of human neonatal keratinocytes. A metabolic
      inhibitor of proteoglycan sulfation was used to assess the role of cellular
      heparin-like glycosaminoglycans in amphiregulin-dependent growth. Keratinocytes
      plated at > 10(3) cells/cm2 grew in an autocrine manner in the absence of
      exogenous epidermal growth factor or amphiregulin. Incubation of keratinocytes
      with an amphiregulin-blocking antibody indicated that approximately 70% of
      autocrine growth is mediated by endogenous amphiregulin. Proliferation potential
      in the presence of recombinant human amphiregulin was dose dependent and
      saturable and above approximately 1 ng/ml was comparable to that achieved with
      similar concentrations of epidermal growth factor. Sodium chlorate, which blocks
      glycosaminoglycan sulfation, reversibly inhibited epidermal growth factor
      dependent proliferation by 42%, exogenous amphiregulin-dependent proliferation by
      75%, and autocrine growth by 95%; concurrent incubation with 1-100 micrograms/ml
      heparin partially reversed this inhibition. Exogenous heparin in the absence of
      chlorate, however, nearly completely inhibited growth under autocrine conditions
      and in the presence of recombinant amphiregulin. Structure-function studies
      indicate that the polymerization level, high sulfate group density, and possibly
      iduronic acid content of heparin-like moieties correlate with their inhibitory
      activity. Collectively, these observations indicate that amphiregulin is the
      major autocrine factor for keratinocytes and demonstrate that exogenous
      amphiregulin is an effective growth promoting factor with molar potency similar
      to that of epidermal growth factor. Autocrine and paracrine signaling by
      amphiregulin may require cellular heparin-like glycosaminoglycans, presumably as
      matrix or membrane proteoglycans, whereas soluble glycosaminoglycans inhibit
      signaling, possibly by competing for cytokine binding.

PMID- 8138580
TI  - Depleted level of heparan sulfate proteoglycan in the extracellular matrix of
      endothelial cell cultures exposed to endotoxin.
AB  - Exposure of cultured endothelial cells to endotoxin causes an increase in the
      amount of cellular heparan sulfate proteoglycan and a depletion of this molecule
      in the extracellular matrix. Concomitant with the decrease in the extracellular
      matrix is the appearance of a fraction of proteoglycan bearing altered
      carbohydrate moieties in the culture medium. beta-mercaptoethanol, mannitol, and
      dimethyl sulfoxide bring back to normal the structural properties of the
      proteoglycan in the medium and restore the matrix content in proteoglycan to a
      level comparable to that of control cells but do not affect the increase in the
      amount of proteoglycan on the cell. This "uncoupling" suggests that two
      independent chains of events underlie the synthetic and structural changes of the
      proteoglycan triggered by endotoxin in the endothelial cell.

PMID- 8138581
TI  - Synthesis of and response to 1,25 dihydroxycholecalciferol by subpopulations of
      murine epidermal keratinocytes: existence of a paracrine system for 1,25
      dihydroxycholecalciferol.
AB  - The epidermis is both a target tissue for and a source of 1,25
      dihydroxycholecalciferol. The present study determines which of the epidermal
      cell populations synthesizes 1,25 dihydroxycholecalciferol and which responds to
      this hormone. Epidermal keratinocytes from new born rat epidermis were separated
      by unit gravity sedimentation into poorly differentiated cells, slow-cycling more
      differentiated cells, actively proliferating cells, and terminally
      differentiating subpopulations. The keratinocyte populations were characterized
      by cell size analysis, cell morphology, and DNA and RNA contents (acridine orange
      flow cytometry). 1,25(OH)2D3 synthesis was studied by measuring the conversion of
      [3H] 25(OH)D3 to [3H] 1,25(OH)2D3. The purified product was tested for its
      ability to compete with synthetic [3H] 1,25(OH)2D3 for binding to chick
      intestinal cytosol. The responses of the keratinocyte subpopulations to exogenous
      1,25(OH)2D3 were evaluated by the increase in 25(OH)D3-24 hydroxylase activity.
      Furthermore the expression of 1,25(OH)2D3 receptors (VDR) was examined in these
      cell populations. The results show that only the least differentiated cells
      produced 1,25(OH)2D3. In contrast, immunocytochemical detection of VDR, the VDR
      mRNA, and a 25(OH)D3-24 hydroxylase response to 1,25(OH)2D3 were mainly found in
      the more differentiated cells. Thus, the ability of epidermis to synthesize
      1,25(OH)2D3 and be simultaneously sensitive to it depends on the state of cell
      differentiation. This suggests that the mammalian epidermis contains a paracrine
      system in which the more differentiated keratinocytes are sensitive to the
      1,25(OH)2D3 produced locally by neighboring immature ones.

PMID- 8138582
TI  - Modifications in the synthesis of membrane-associated chondroitin sulfate
      proteoglycans in hemopoietic progenitor cells are accompanied by alterations in
      their adhesive properties.
AB  - In vitro studies in our laboratory have indicated that murine hemopoietic
      progenitor cell (HPC) lines, irrespective of their differentiation stage,
      synthesize and accumulate in the cell membrane a unique species of chondroitin
      sulfate proteoglycan (CS-PG). It has been postulated that CS-PG participates in
      HPC adhesion to pericellular stromal fibronectin by interacting with its heparin
      promoting binding region. To further support this contention, we first attempted
      to modify CS-PG synthesis in HPC by the use of chlorate and p-nitrophenyl beta-D
      xyloside, which inhibit sulfation and glycosaminoglycan (GAG) addition in
      proteoglycans, respectively. We then studied the effect that these modifications
      may have in the adhesive capacity of HPC to interact with fibronectin and its
      cell- and heparin-promoting binding chymotryptic fragments. Treatment with
      chlorate which resulted in a decreased sulfation of membrane-associated 35 S
      labeled CS-PG, as judged by ion exchange chromatography, did not affect HPC
      adhesion to fibronectin or its fragments. However, beta-xyloside treatment which
      reduces the abundance of membrane-associated CS-PG, as evidenced by molecular
      sieve chromatography, produced a major and specific decrease in HPC adhesion to
      the heparin-promoting binding fragment of fibronectin. These results indicate
      that CS-PG are involved in HPC interaction with fibronectin, in a mode that seems
      to be dependent on the differentiation stage of HPC.

PMID- 8138583
TI  - Failure of infinite life span human cells from different immortality
      complementation groups to yield finite life span hybrids.
AB  - The observation that fusion of infinite life span cells with finite life span
      cells produces hybrid cells with finite life spans led to the conclusion that an
      infinite life span in culture is a recessive trait resulting from loss of the
      function of a gene or genes that contribute to an active program for cellular
      senescence. Furthermore, finding that certain pairs of infinite life span cells,
      when fused to one another, can complement each other to yield finite life span
      hybrids allowed 30 infinite life span cell lines to be assigned to four
      immortality complementation groups (Pereira-Smith and Smith, 1988, Proc. Natl.
      Acad. Sci. U.S.A., 85:6042). In the present study, we fused a chromosomally
      stable, near diploid, morphologically normal, infinite life span cell strain,
      designated MSU-1.1, with its normal, finite life span, precursor cell strain and
      obtained finite life span hybrids, as expected if infinite life span in culture
      is a recessive trait. However, 14 of the 14 hybrids from our fusions of MSU-1.1
      cells with representative cell lines from each of the four immortality
      complementation groups, and 38 of the 39 hybrids from our fusions of infinite
      life span cells that have been reported to complement each other, failed to
      exhibit finite life spans. This result suggests that infinite life span cells
      cannot complement each other to yield finite life span hybrids. In examining this
      unexpected result, we obtained evidence that long-term dual drug selection can be
      deleterious to hybrid cells even though they carry resistance markers for both
      drugs, indicating that the cell death of such hybrids observed in other studies
      may have resulted from the cytotoxic effect of long-term drug selection, rather
      than from senescence.

PMID- 8138584
TI  - Dependence of collagen remodelling on alpha-smooth muscle actin expression by
      fibroblasts.
AB  - To study the relation between expression of the putative myofibroblast marker
      alpha-smooth muscle actin and the remodelling of extracellular matrix,
      immunocytochemical, gel electrophoresis, and collagen gel contraction studies
      were performed on two human fibroblast subtypes. Double immunolabelling for total
      actins and alpha-smooth muscle (sm) actin as well as affinity labelling of
      filamentous and monomeric actins in gingival fibroblasts demonstrated that alpha
      sm was colocalized in stress fibres and in regions with high levels of monomeric
      actin throughout the cytoplasm. alpha-sm comprised up to 14% of total cellular
      actin as assessed by 2D gel electrophoresis. Thirteen different gingival and
      seven different periodontal ligament fibroblast lines constitutively expressed on
      alpha-sm actin. These cells exhibited up to 60% inter-line variations of
      fluorescence due to alpha-sm actin and up to 70% and 45% inter-line variation in
      the rate of collagen gel contraction. Quantitative, single cell fluorimetry of
      alpha-sm actin immunoreactivity demonstrated a linear relation between gel
      contraction and alpha-sm actin (correlation coefficients of 0.71 for gingival and
      0.61 for periodontal ligament cells), but there was no detectable relationship
      between total actin content and gel contraction. In contrast, flow cytometry
      demonstrated that 99% of the total gated cells from cell lines exhibiting rapid
      gel contraction showed alpha-sm actin staining above background fluorescence as
      compared to only 35% of cells with slow rates of gel contraction. Contracting
      collagen gels stained with FITC-phalloidin showed cells with well-developed
      stress fibres that were progressively more compact and elongated during the time
      of maximal gel contraction. To examine the dependence of gel contraction on
      assembly of monomeric actin into actin filaments, cells were electroporated in
      the presence of phalloidin or cytochalasin D. Collagen gels exhibited up to 100%
      inhibition of gel contraction that was dose-dependent. Gel contraction was
      inhibited 93% by electroinjection of cells with alpha-sm actin antibody prior to
      incubation, but the antibody did not inhibit actin assembly after attachment and
      spreading on substrates. These data indicate that gel contraction is dependent on
      alpha-sm actin expression and that alpha-sm actin is a functional marker for a
      fibroblast subtype that rapidly remodels the extracellular matrix.

PMID- 8138585
TI  - Ligation of CD3 triggers transmembrane proximity between LFA-1 and cortical
      microfilaments in a cytotoxic T cell clone derived from tumor infiltrating
      lymphocytes: a quantitative resonance energy transfer microscopy study.
AB  - We have explored the transmembrane associations of leukocyte function associated
      antigen-1 (LFA-1) in response to T cell receptor ligation using resonance energy
      transfer (r.e.t.) microscopy to detect receptor to microfilament proximity.
      R.e.t. was detected using both imaging and photon counting techniques. T cells
      were labeled with fluorescein-conjugated F(ab')2 fragments of an anti-LFA-1
      monoclonal antibody. Cells were incubated at 37 degrees C on unmodified glass
      surfaces and surfaces coated with anti-CD3 or anti-H-9 antibodies. Microfilaments
      of fixed cells were labeled with rhodamine-phalloidin. R.e.t. was not affected on
      unmodified (blank) or irrelevant antibody-treated (H-9) surfaces. However, both
      fluorescence images and photon count rates were significantly enhanced when cells
      bound to anti-CD3-coated surfaces. This enhancement was not due to a general
      effect of T cell activation on transmembrane cytoskeletal proximity since CD45
      phalloidin r.e.t. was not affected by CD3 ligation. These experiments provide
      direct physical evidence that ligation of the CD3 complex specifically increases
      the proximity of LFA-1 and microfilaments, which may be relevant to T cell
      mediated adherence reactions.

PMID- 8138586
TI  - Electrogenic Na-K pump current in rat skeletal myoballs.
AB  - Catecholamines and insulin have been reported to hyperpolarize skeletal muscle
      fibers via stimulation of the electrogenic Na-K pump (Flatman and Clausen, 1979,
      Nature, 281:580-581). Therefore, the electrogenic Na-K pump current was
      investigated in cultured colcemid-treated rat skeletal myoballs using whole-cell
      voltage clamp. Skeletal muscles were taken from newborn rat hindlegs, trypsin
      digested, and cultured. By day 7, all myoblast cells fused into myotubes. After
      treatment with the microtubule disrupter colcemid (10(-7) M) for 2 days, some of
      the myotubes became transformed into spherical myoballs, having an average
      diameter of 41.2 +/- 1.5 microns (n = 21). The resting membrane potential
      averaged -56.8 +/- 1.7 mV (n = 40). Ouabain (1 mM) quickly depolarized the
      myoballs to -51.1 +/- 1.1 mV (n = 27), showing the existence of an electrogenic
      Na-K pump in the skeletal myoball preparation. The values for the specific
      membrane resistance and capacitance were 5.5 +/- 1.0 K omega-cm2 (n = 21) and 3.7
      +/- 0.3 microF/cm2 (n = 21), respectively. The pump current averaged 0.28 +/-
      0.03 pA/pF (n = 10), with the membrane potential at -60 mV and 10 mM intrapipette
      Na+. The Na-K pump contribution to resting membrane potential was calculated to
      be 5.7 mV, matching the ouabain-induced rapid depolarization. When the Na-K pump
      was stimulated with 50 mM intrapipette Na+, the pump current was about doubled
      (0.52 +/- 0.08 pA/pF; n = 10). Isoproterenol (1 microM) and 8-Br-cAMP (1 mM) also
      significantly increased pump current by 50% (0.42 +/- 0.04 pA/pF; n = 9) and 64%
      (0.46 +/- 0.09 pA/pF; n = 7), respectively. In contrast, although insulin and
      phorbol ester also increased pump current, this increase was not statistically
      significant. The ineffectiveness of insulin and phorbol ester may be due to
      colcemid interfering with Na-K pump translocation from internal vesicles to the
      sarcolemma.

PMID- 8138587
TI  - Induced expression of p52(PAI-1) in normal rat kidney cells by the microfilament
      disrupting agent cytochalasin D.
AB  - In established normal rat kidney (NRK) cells, synthesis of the 52 kDa type-1
      inhibitor of plasminogen activator [p52(PAI-1)] is stimulated by the cell shape
      modulating fungal metabolite cytochalasin D (CD). Induction paralleled the time
      course of morphologic change and reflected relatively specific increases in
      saponin-resistant p52(PAI-1) protein accumulation (approximating ten- to thirty
      fold over control) and mRNA abundance (seven- to nine-fold). Augmented p52 (PAI
      1) mRNA levels closely correlated with increases in 43 kDa p52(PAI-1) core
      protein biosynthesis. Sensitivity to tunicamycin indicated that N-linked post
      translational modifications to this 43 kDa core species generated the full
      complement of 50 kDa (intermediate) and 52 kDa (mature) p52(PAI-1) glycosylated
      isoforms. CD-induced p52(PAI-1) expression occurred efficiently in quiescent NRK
      cells maintained under serum-free conditions as well as in fully serum
      supplemented actively growing cultures. While 8-bromo-cAMP reduced both
      constitutive and transforming growth factor-beta-induced p52(PAI-1) synthesis by
      > 50%, no such inhibition was evident in short-term (4 h) CD-stimulated cultures.
      Long-term (24 h) exposure of NRK/CD cells to 8-bromo-cAMP did result in an
      approximately 34% reduction in stimulated p52(PAI-1) expression, however, levels
      expressed by NRK/CD+cAMP populations remained markedly elevated relative to
      control values. These data suggest the existence of a cell shape-dependent aspect
      of p52(PAI-1) expression control distinct from both the constitutive and growth
      factor-mediated pathways of gene regulation.

PMID- 8138588
TI  - Identification of an IP3 receptor in endothelial cells.
AB  - In this study we have used saponin to permeabilize bovine endothelial cell
      membranes in order to directly test the involvement of IP3 in regulating internal
      Ca2+ release. Our results indicate that the release of internal Ca2+ occurs as
      early as 1-3 seconds after IP3 addition. This IP3-induced internal Ca2+ release
      can be inhibited by heparin (an IP3 receptor antagonist). Further binding of
      [3H]IP3 to saponin-permeabilized bovine endothelial cells reveals the presence of
      a single, high affinity class of IP3 receptor with a dissociation constant (Kd)
      of approximately 0.50 (+/- 0.03) nM. Using a panel of monoclonal and polyclonal
      antibodies against IP3 receptor, we have established that the bovine endothelial
      cell IP3 receptor (approximately 260 kDa) displays immunological cross-reactivity
      with the rat brain IP3 receptor. Immunofluorescence data indicates that the IP3
      receptor is preferentially located at the perinuclear region of the cells. In
      addition, PCR analysis of first-strand cDNAs from both bovine endothelial cells
      and rat brain tissues reveals that the IP3 receptor transcript in bovine
      endothelial cells belongs to the short non-neuronal form and not the long
      neuronal form detected in rat brain tissue. These findings suggest that the IP3
      receptor in endothelial cells is both structurally and functionally analogous to
      that reported in non-neuronal cell systems and probably plays an important role
      in agonist-induced endothelial cell activation.

PMID- 8138589
TI  - Stimulation of hepatocyte DNA synthesis by prostaglandin E2 and prostaglandin F2
      alpha: additivity with the effect of norepinephrine, and synergism with epidermal
      growth factor.
AB  - Previous data obtained in vivo and in vitro suggest that both prostaglandins
      (PGs) and catecholamines may have a role in promoting hepatocyte proliferation,
      and PGE2 and PGF2 alpha have also been implicated as mediators of the mitogenic
      actions of epidermal growth factor (EGF) (and transforming growth factor alpha
      [TGF alpha]). We have studied the effects of PGs and norepinephrine on DNA
      synthesis in serum-free primary cultures of rat hepatocytes, and compared the PG
      effects with those of norepinephrine. PGE2, PGF2 alpha, PGD2, and the synthetic
      analog dimethyl-PGE2 markedly enhanced the DNA synthesis. A more quantitative
      analysis of the effects of PGE2 and PGF2 alpha on the DNA synthesis, in the
      presence and absence of EGF, indicated that these PGs interacted in an
      essentially multiplicative manner with the effect of EGF. The effects of PGE2 and
      PGF2 alpha showed almost complete additivity with the stimulation of DNA
      synthesis produced by maximally effective concentrations of norepinephrine. The
      data suggest a) that PGE2 and PGF2 alpha facilitate and synergize with, rather
      than mediate, the actions of EGF in hepatocytes, and b) that this effect of the
      PGs occurs by mechanisms that are at least partly distinct from those of
      norepinephrine.

PMID- 8138590
TI  - Coordinate and independent regulation of alpha B-crystallin and hsp27 expression
      in response to physiological stress.
AB  - alpha-Crystallins share structural and functional properties with the stress
      protein hsp27. These polypeptides are expressed at low constitutive levels in
      many tissues including brain, and alpha B-crystallin and hsp27 can accumulate in
      central nervous system glia in a variety of neurological conditions. We report
      here that heat shock and exposure to transition metals result in an increase in
      the steady state mRNA level of alpha B-crystallin and hsp27 in primary cultures
      of rat forebrain astrocytes. Both exposure to tumour necrosis factor-alpha and
      hypertonic conditions result in alpha B-crystallin mRNA accumulation but no
      change in the hsp27 mRNA level. Under some of these conditions increased
      synthesis and accumulation of alpha B-crystallin and hsp27 protein are also
      evident. We are unable to detect alpha A-crystallin mRNA in resting or stressed
      astrocytes. A novel phenomenon involving a transitory change in stress protein
      mRNA mobility in Northern blots during induction is reported, which is stress
      type and cell type independent. The results demonstrate multiple stress
      regulation of alpha B-crystallin and hsp27 in cultured astrocytes, suggesting
      that they can legitimately be regarded as stress proteins in the central nervous
      system.

PMID- 8138591
TI  - Plasma membrane K+/H(+)-ATPase from Leishmania donovani.
AB  - Leishmania donovani has an active K+/H+ exchange system on the surface membrane.
      Modulation of external K+ concentration resulted in a corresponding change in
      internal pH (pHi) suggesting a link between proton and potassium transport.
      Although a Na+/H+ antiporter is present on the plasma membrane, its sensitivity
      to amiloride suggests that it operates independent of K+/H+ exchange. Reduction
      of cellular ATP with NaN3 and KCN inhibits K+/H+ exchange showing thereby that
      the process is energy dependent. The K+/H+ exchange is sensitive to inhibitors of
      the gastric K+/H(+)-ATPase. It is concluded that the H(+)-ATPase previously
      reported on the plasma membrane of L. donovani is in fact a K+/H(+)-ATPase.

PMID- 8138592
TI  - Transforming growth factor beta 1 augments mitogen-induced prostaglandin
      synthesis and expression of the TIS10/prostaglandin synthase 2 gene both in Swiss
      3T3 cells and in murine embryo fibroblasts.
AB  - Transforming growth factor-beta (TGF-beta), a potent cytokine, modulates a wide
      variety of biological responses. Among its actions, TGF-beta can augment
      prostaglandin synthesis in several cell types. Although TGF-beta alone has no
      effect on prostaglandin production in Swiss 3T3 cells, we find that TGF-beta
      augments the ability of tetradecanoyl phorbol acetate (TPA) or serum to stimulate
      PGE2 production. The TIS10 gene is a primary response gene encoding a second form
      of prostaglandin synthase (PGS), the rate-limiting enzyme in the biosynthesis of
      prostaglandins, thromboxanes, and prostacyclins from arachidonic acid. TIS10/PGS
      2 expression is induced by mitogens in Swiss 3T3 cells. TGF-beta also augments
      mitogen-induced synthesis and accumulation of TIS10/PGS-2 protein and induction
      of TIS10/PGS-2 message in Swiss 3T3 cells. In contrast, TGF-beta has little or no
      effect on the level of PGS-1 (EC1.14.99.1) message, either alone or in concert
      with TPA or serum. TGF-beta concentrations in the range of 0.01-0.10 ng/ml (0.4
      4.0 pM) maximally enhance mitogen induction of TIS10/PGS-2 message. TPA-induced
      accumulation of unspliced TIS10/PGS-2 transcript is augmented by TGF-beta,
      suggesting that this cytokine exerts its effect on expression of the TIS10/PGS-2
      gene by transcriptional regulation. TGF-beta also augments TPA-induced
      prostaglandin production, TIS10/PGS-2 antigen accumulation, and TIS10/PGS-2
      message induction in primary cultures of mouse embryo fibroblasts. Dexamethasone
      attenuates TGF-beta enhancement of all these mitogen-induced responses: PGE2
      accumulation, appearance of TIS10/PGS-2 protein and message, and accumulation of
      TIS10/PGS-2 unprocessed transcript.

PMID- 8138593
TI  - Recombinant human bone morphogenetic protein-2 enhances expression of interleukin
      6 and transforming growth factor-beta 1 genes in normal human osteoblast-like
      cells.
AB  - The process of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced
      endochondral ossification involves 1) the proliferation and differentiation of
      mesenchymal cells into chondroblasts and osteoblasts; 2) the production and
      maturation of cartilage and bone matrix; and 3) the differentiation of
      circulating osteoclast precursor cells into osteoclasts. Currently the molecular
      mechanisms of these complex sequential events are unknown. It seemed reasonable
      to us to assume that communication between cells through soluble mediators during
      bone induction by rhBMP-2 may play an important role in the sequential
      differentiation of chondroblasts, osteoblasts, and osteoclasts. We have therefore
      used a human osteoblast-like initial transfectant cell line (HOBIT) to study the
      effect of rhBMP-2 on gene expression of interleukin-6 (IL-6) and transforming
      growth factor-beta 1 (TGF-beta 1), both of which affect osteogenesis and
      ostoeclastogenesis. Our results have demonstrated that rhBMP-2 acts on HOBIT
      cells to stimulate expression of IL-6 and TGF-beta 1 genes and the production of
      IL-6. Enhancement of gene expression of IL-6 and TGF-beta 1 by rhBMP-2 was both
      sensitive (half maximal effect at approximately 10 ng/ml) and potent (maximum
      induction was approximately four and threefold greater than controls,
      respectively). Time course studies showed that the induction of TGF-beta 1 and IL
      6 mRNA occurs within short periods--4 and 8 hours after exposure to rhBMP-2,
      respectively. Interestingly, these effects, however, were not accompanied by the
      mitogenic action of rhBMP-2. It suggests that rhBMP-2 enhances IL-6 and TGF-beta
      1 production during osteogenesis and at least in part mediates the complex
      sequential differentiation of chondroblasts, osteoblasts, and osteoclasts during
      rhBMP-2-induced endochondral ossification.

PMID- 8138594
TI  - Mitosis and cytokinesis in subconfluent endothelial cells exposed to increasing
      levels of shear stress.
AB  - An in vitro flow apparatus in combination with cultured endothelium was used to
      determine the effects of fluid-generated shear stress on cells undergoing mitosis
      and cytokinesis. Cell responses were recorded by time-lapse video microscopy
      under phase contrast or Hoffman modulation contrast optics. Completion of cell
      division in mitotic cells was dependent upon both the initial presence of
      intercellular attachments and the magnitude of fluid wall shear stress. In
      nonisolated populations, 95.3%, 69.5%, and 57.1% of the cells completed cell
      division as opposed to 66.6%, 20.4%, and 11.9% in the isolated cell groups at
      2.8, 14.1, and 33 dynes/cm2, respectively. Prestressing cells for 14 h prior to
      monitoring failed to increase retention of isolated mitotic cells. The presence
      of neighboring cells facilitated replication by providing an anchoring attachment
      or a luminal surface for completion of division. Cell detachment most commonly
      occurred at the onset of cytokinesis when substrate contact areas were minimal
      and focal contacts were absent. A comparison between no flow controls and shear
      stress specimens indicated no significant differences in transit times for
      mitosis and cytokinesis. Thus, subconfluent endothelial cells may be more
      susceptible to detachment during cell division due to increases in shear stress,
      the absence of intercellular attachments, and reduced cell-substrate contacts.

PMID- 8138596
TI  - Academic advisement and the RN-to-BSN student.
AB  - Recognizing the advisement needs of registered nurse students pursuing a
      baccalaureate in nursing while managing employment, family, and academic
      obligations is important. The most useful academic advising functions identified
      were advice on requirements and registration with respondents indicating self
      monitoring of their degree progress. Respondents represented characteristics of
      adult learners who preferred scheduled interviews for advisement with apparent
      themes of firmness and availability of the academic adviser and flexibility in
      requirements.

PMID- 8138595
TI  - Growth regulation of human glioblastoma T98G cells by insulin-like growth factor
      1 and its receptor.
AB  - The interaction of insulin-like growth factors (IGFs) with the IGF-1 receptor is
      an important step in the control of cell proliferation and development. In
      particular, IGF-1 and IGF-2 are key regulators of central nervous system
      development, and may modulate the growth of glial tumors. We have investigated
      the growth factor regulation of the human glioblastoma cell line T98G. These
      cells growth arrested in serum-free medium at 34 degrees C, despite their
      secretion of substantial amounts of bioactive IGF-1. To be stimulated to divide,
      growth-arrested cells required the addition of platelet-derived growth factor
      (PDGF) or its equivalent, 1% serum. Cell proliferation in serum-free medium could
      also be obtained by shifting the cells to a temperature of 39.6 degrees C.
      Treatment of growth-arrested cells with PDGF or temperature shift was accompanied
      by a transient increase in the expression of the mRNA for the IGF-1 receptor.
      Transfection with a plasmid constitutively expressing the full cDNA for the human
      IGF-1 receptor allowed autonomous growth in serum-free medium at 34 degrees C. By
      contrast, growth induction by growth factors or temperature shift was abrogated
      by transfection of the cells with a plasmid expressing a 300 bp segment of mRNA
      antisense to the IGF-1 receptor mRNA. Cloning in soft agar was also inhibited by
      expression of antisense IGF-1 receptor mRNA. These results demonstrate that the
      IGF-1 receptor is strictly required for the growth of T98G glioblastoma cells.
      Moreover, the autocrine interaction of IGF-1 with its receptor regulates both
      autonomous and anchorage-independent growth of these cells.

PMID- 8138597
TI  - The Taste of Nursing: an initiative to attract a new type of nursing student.
AB  - Across the nation, a new group of students is electing to enter nursing--those
      with degrees or work experience in other areas. To address the special needs of
      these individuals, Taste of Nursing was developed by faculty in a school of
      nursing in conjunction with local hospitals. This three-session adult education
      workshop was designed to increase participants' understanding of the
      satisfaction, frustrations, and opportunities within nursing as well as routes to
      preparation for this career. Suggestions are presented for program variations
      that might broaden the workshop's scope.

PMID- 8138598
TI  - The nursing assessment decision grid: tool for delegation decision.
AB  - The ability of registered nurses to delegate patient care to nurse extenders has
      become an important skill. This study measures the effectiveness of the Nursing
      Assessment Decision Grid to teach RNs delegation skills. The ability of 93 staff
      nurses to analyze tasks and problems found in two patient vignettes and then
      delegate some care to an LVN working in a dyad was measured before and after
      exposure to the Nursing Assessment Decision Grid. A paired sample t test was used
      to compare mean pretest and posttest scores for the three parameters. Analysis of
      variance was used to examine the effect of professional and personal experiences
      on this decision making ability. RNs showed a statistically significant increase
      in their ability to identify nursing tasks and patient problems embedded in two
      vignettes. They were then able to make delegation decisions about the care of the
      patients in the vignettes. Primary language of the study subject may have had an
      effect on the ability to perform patient problem analysis.

PMID- 8138599
TI  - Use of the nursing simulation laboratory in reentry programs: an innovative
      setting for updating clinical skills.
AB  - Nurses who have been inactive for five or more years are deficient in technical
      skills and have high levels of anxiety regarding these deficiencies. Collegiate
      school of nursing laboratories are ideal settings to provide skill practice,
      reduce fear regarding new technology, and restore confidence of returnees. This
      article describes the laboratory component of a clinical update course that uses
      principles of adult education and self-pacing through independent learning
      stations to teach contemporary nursing skills. A description of instructional
      resources and equipment used to facilitate the practice is included.

PMID- 8138600
TI  - Nursing skills fair: gaining knowledge with fun and games.
AB  - The body of nursing knowledge continues to expand and the Joint Commission on
      Accreditation of Healthcare Organizations (JCAHO) mandates managers and educators
      to maintain competence in their nursing staff members. Stricter reimbursement
      criteria for hospital care, however, severely restrict education budgets.
      Educational programs can be offered at a reasonable cost without putting the
      adult learner to sleep! The development and implementation of a successful
      nursing skills fair is discussed.

PMID- 8138601
TI  - Nurses' attitudes toward nursing process as measured by the Dayton Attitude
      Scale.
AB  - This study measured the knowledge of and attitudes toward the nursing process
      held by nurses who provide direct patient care. The Dayton Attitude Scale Toward
      Care Planning (DASC) was returned by 1,096 nurses practicing in nine hospitals.
      Overall, participants were knowledgeable of the nursing process and held a
      relatively positive attitude toward the nursing process and nursing diagnosis.
      Higher nursing degrees were associated with more positive attitudes. The most
      common barrier to the use of the nursing process was insufficient time. The study
      found that less than 30% of the subjects liked the way care planning was done.
      These findings suggest that improving care planning systems would further promote
      consistency in the process.

PMID- 8138602
TI  - Increasing standards awareness through a fortune cookie contest.

PMID- 8138603
TI  - State and association/certifying boards CE requirements.

PMID- 8138604
TI  - Role of continuing educators in encouraging use of clinical practice guidelines.
AB  - With the current emphasis on outcomes and quality improvement, continuing
      educators need to encourage the use of clinical practice guidelines. Specific
      strategies to assist educators with this task are outlined. Use of clinical
      practice guidelines can facilitate research linking interventions and outcomes
      and lead to practice that is both more scientific and cost-effective.

PMID- 8138605
TI  - Social and family factors in adolescent psychiatry.
AB  - A retrospective analysis of referrals to a regional adolescent psychiatric
      service over two years was conducted, focusing on selected social and family
      variables, to identify areas of potential unmet need and the relationship between
      these factors and clinical variables. Social and family disadvantage was well
      represented in our patients, but few were over the age of 17 and fewer from
      ethnic minority backgrounds. Associations between social, family factors,
      diagnostic and treatment variables are presented and their implications
      discussed.

PMID- 8138606
TI  - Heterosexual behaviour of 18-year-olds in the Glasgow area.
AB  - This paper describes heterosexual behaviour, and protection against pregnancy and
      sexually transmitted diseases, among 908 18-year-olds in the Glasgow area in
      1990. The proportion who reported having experienced sexual intercourse was
      similar to, though slightly lower than, that reported in most recent studies
      elsewhere. There were marked sex differences, with males reporting being
      significantly younger at first intercourse and having had more sexual partners
      than females. The reported prevalence of unprotected sex (without any
      contraception) and of "unsafe" sex (without a condom) was high. Being male, of no
      religious affiliation, an early school leaver, and not in higher education were
      independently associated with sexual experience. Among the sexually experienced,
      lower education was also associated with "unsafe" sex, and Catholicism with
      unprotected sex. The overall pattern of findings, particularly in relation to sex
      differences, suggests that young people in the Glasgow area may be subject to
      more traditional influences than those elsewhere.

PMID- 8138607
TI  - Developmental issues in the assessment and treatment of adolescent perpetrators
      of sexual abuse.
AB  - Sexual abuse perpetrated by adolescents is not recognized as a major problem.
      While there may be similarities between adults and adolescents who perpetrate
      sexual abuse, adolescent sexual abusers face developmental issues which are
      different from those of adults. It is argued that the specific needs of the
      adolescent sexual abuser cannot be fully understood by simply extrapolating
      knowledge derived from work with adult perpetrators. The purpose of the present
      paper is to discuss the importance of the developmental issues facing the
      adolescent perpetrator of sexual abuse and their implications for the assessment
      and treatment of this group of sexual abusers.

PMID- 8138608
TI  - Unemployment and mental health among young people: a longitudinal study.
AB  - In a longitudinal study, a representative sample of nearly 2000 young people (17
      20 years) was followed up in 1985, 1987 and 1989. The Central Bureau of
      Statistics in Norway was responsible for the collection of data. The results
      showed that unemployment had a weak but significant impact upon mental health
      problems. Active job seeking did not seem to moderate the mental health problems
      experienced by the unemployed. Social support and contact with close friends had
      a moderating effect upon nervous symptoms in women but not in men. Unemployed men
      who were especially involved in illegal activity showed increased nervous
      symptoms during unemployment.

PMID- 8138609
TI  - The effects of pubertal changes on body image and relations with peers of the
      opposite sex in adolescence.
AB  - The purpose of this research was to study the impact of pubertal maturation on
      body image and on the perceived quality of relations with opposite sex peers in
      adolescence. A sample of 157 French adolescents aged from 11 to 16 years filled
      in self-report scales; physical development was measured by physicians using
      Tanner criteria (pubic hair, genitalia and breast growth). Results of ANOVAs
      confirmed that boys evaluate themselves on attractiveness more positively than
      girls, and showed no difference between the sexes on perceived physical
      condition. Multiple regression analyses revealed different effects--according to
      sex--of pubertal status on body image and relations with opposite sex peers.
      Correlational patterns suggested that the experience of the body and the
      experience of relations with opposite sex peers are not built in the same way in
      girls and boys during adolescence.

PMID- 8138610
TI  - Parental disclosure from the perspective of late adolescents.
AB  - Although parental relations are considered influential in adolescents' transition
      to adulthood, we know little about lessons that parents provide through self
      disclosure. This study explored the content and extent of parents' disclosure,
      from the perspective of their children in late adolescence. College students were
      asked to indicate how much each parent had shared about various matters in their
      lives, to characterize the quality of each parent's disclosure to them and their
      disclosure to each parent, and to recall each parent's most meaningful, awkward
      and first disclosures. Based on previous research regarding adolescents'
      disclosure to parents, gender differences in disclosure, and reciprocity of
      disclosure, it was predicted that greater disclosure would be exchanged with
      mothers than with fathers. Results confirmed initial predictions, indicated some
      of the functions that parental disclosure may serve, and suggested a model by
      which intra-family disclosure might evolve.

PMID- 8138611
TI  - Anxiety and autonomy in adolescence among father-orphaned kibbutz children.
AB  - The aim of the study was to measure levels of anxiety and autonomy in non
      clinically referred kibbutz orphaned and non-orphaned adolescents. The
      performance of 28 kibbutz adolescents orphaned when aged 2-10 was compared to 42
      non-orphaned kibbutz adolescents on the Manifest Anxiety Scale for Israeli
      Children, the Autonomy of the Child Test and on a general data questionnaire.
      Results showed that when total populations were considered, no significant
      differences were found on levels of manifest anxiety and levels of autonomy. When
      the groups were further broken down according to gender and age, it was found
      that older orphan girls manifested significantly greater anxiety than any group
      and significantly lower autonomy than older non-orphan girls. A rationale linking
      the vulnerability of older orphan girls to adolescent developmental theory is
      suggested.

PMID- 8138612
TI  - Facilitating primary health care.

PMID- 8138613
TI  - Long-term care reform in Alberta, Canada: the role of the resident classification
      system.
AB  - In 1988 the Alberta government, Canada, introduced a patient (now called
      resident) classification system (RCS) to measure the care requirements of
      residents in long-term care facilities and provide case-mix information so that
      funding could be based on resident need rather than a system of global funding.
      The RCS is described and issues relating to the measurement of patient/resident
      need are discussed, together with some suggestions as to how the tool might be
      used in quality assurance and outcome measurement.

PMID- 8138614
TI  - A comparative study of the attitudes of nursing and medical students to aspects
      of patient care and the nurse's role in organizing that care.
AB  - The purpose of this study was a comparative analysis of the attitudes of nursing
      and medical students toward some issues relating to patient care and the role of
      the nurse in organizing that care. The data were collected from 11 medical
      students and 19 undergraduate nursing students in their fourth or final year of
      study. Findings suggested that there was a statistically significant difference
      in the attitudes of both groups of students to the areas under investigation.
      Medical students were rather more cure-oriented than nursing students who showed
      a care orientation. Further, the nursing students had a more positive attitude
      towards the need for a nursing assessment than their medical colleagues. Finally
      there was a marked difference in the way in which each group perceived the
      nurse's role, the nursing students emphasizing its independent scope while the
      medical students were less convinced on this issue. The conclusions suggest that
      both nursing and medical students need to develop a mutual understanding and
      respect for each other's roles if interprofessional relations are to improve.

PMID- 8138615
TI  - An exploration of the taken-for-granted world of the cancer nurse in relation to
      stress and the person with cancer.
AB  - This paper focuses upon an exploration into the world of the cancer nurse
      regarding stress and persons with cancer. It is proposed that the cancer nurse's
      world often is not emphasized or even acknowledged within clinical practice and,
      for the most part, remains ignored. It is argued that the cancer nurse's world is
      rich with meaning, and the knowledge, skills and values within this domain need
      to come to the fore. A phenomenological approach was adopted for the study,
      because of the inherent emphasis upon meaning and understanding within the cancer
      nurse's everyday practice. Methodological triangulation involved qualitative
      interviews with nursing staff on an acute oncology unit, observation of the
      nursing admission assessments of cancer patients and use of archival sources
      (nursing kardexes). Content analysis of the interview findings revealed that the
      common-sense understandings of the cancer nurse were present in relation to
      stress and the person with cancer. Although these construals have not been
      adequately studied, the framework of common-sense knowledge involves the informal
      views and the wealth of knowledge individuals have. Common-sense construals are
      linked to the nurses' experience, both past and present, and derived from both
      professional practice and educational experiences. In practice, however, the
      nurses often failed to rely on this knowledge, apparently because of the
      mainstream influence of the medical model. The study led to the recommendation
      reported on in this paper that nurses must bring their common-sense knowledge and
      values to the fore in order to provide holistic care of persons with cancer.

PMID- 8138616
TI  - On sources of powerlessness in nursing home life.
AB  - As feelings of identity and integrity are important for old people's efforts to
      maintain a healthy life, experiences of powerlessness ought to be prevented. This
      paper describes sources of powerlessness in nursing home life. Participant
      observations regarding lucid, elderly patients were undertaken in two Swedish
      nursing home wards. The observations focused on interactions on the wards,
      observed patient reactions and structural/functional conditions of life on the
      wards. The constant, comparative analysis searched for events or conditions which
      seemed to result in reactions signifying positive or negative experiences.
      Tender, loving care, strong cohesion and affection between patients and personnel
      were typical of the observations, yet patients complained of imprisonment,
      powerlessness and hopelessness. Observations are reported as related to
      legitimate, reward, expert, informational and reference power, self
      confidence/respect and socialization. Also existential sources of powerlessness
      were identified. It is concluded that many factors co-operate to create feelings
      of powerlessness in the patients. Empowerment measures are suggested on
      organizational, interactional and personal levels.

PMID- 8138617
TI  - Nurse practitioner: redefining the role of the community nurse?
AB  - Currently there is considerable uncertainty regarding the future for community
      nurses in the United Kingdom (UK). Within the present social and political
      context the development of the nurse practitioner is examined as one possible
      means of redefining the role of some community nurses. The historical development
      of the nurse practitioner in the United States of America (USA) and the UK
      reveals that such a role has, previously, been a response to changing health
      trends and to deficits in the provision of care to communities. The evolution of
      an independent nurse practitioner role is suggested as a way forward for
      different groups of community nurses and should enable them to meet the health
      demands of people in a variety of settings. The 'needs' of patients and clients
      and a multidisciplinary approach are emphasized as being important to the
      redefinition of community nursing roles. The preparation of community nurses as
      nurse practitioners would have obvious implications for community education; this
      matter is briefly discussed. The future of nursing as a whole is set to change;
      it is imperative that all nurses delivering patient care in this arena should
      examine the changing needs of society in the context of political reform, and
      consider how their roles may be developed and redefined.

PMID- 8138618
TI  - Nursing as a career choice for women in Pakistan.
AB  - This paper reports on semi-structured interviews with 114 Pakistani nurses. This
      sample comes from a larger long-term study examining the impact of advanced
      training in Canada on the lives and careers of nurses and lady health visitors
      from Pakistan. The data reported here were drawn from the first interview with
      all nurses, and focuses on how and why they chose a career in nursing.
      Demographically, the respondents (Rs) were more urban and more highly educated
      than the average Pakistani woman. Compared to the national population, Ismailis
      and Christians were over-represented and non-Ismaili Muslims under-represented in
      our sample. Although these ratios are also true of Pakistan's nursing population,
      the bias has been exaggerated by the convenience nature of our sample drawn
      primarily from the Aga Khan University Medical Centre. Most Rs found out about
      nursing through a relative or friend who was also a nurse. Eighty per cent of Rs
      (n = 92) reported having made the decision to pursue nursing by themselves,
      illustrating the increasing ability of women to control their own lives in this
      traditionally patriarchal society. 'Professionalism' was the predominant reason
      why Rs (or others) decided on nursing, followed by 'Altruism'. These findings are
      compared to other studies on the career choice of nurses done in non-Islamic
      societies. Over 90% of Rs reported receiving support from at least one friend or
      relative for their decision to enter nursing. Nonetheless, over half (58%) also
      reported that someone, most often a male relative, had opposed their career
      choice. Our results are discussed in terms of the status of women and nursing in
      Pakistan.

PMID- 8138619
TI  - Keeping it secret: the costs and benefits of nursing's hidden work in discharging
      patients.
AB  - Workload analysts and nursing theorists alike continue their attempts to capture
      the hidden work of nursing, with varying degrees of success. An interpretative
      study of the process of discharging patients from hospital to care at home led to
      a new understanding of the context-related work which nurses do. Three components
      of context-related work were identified: working with the characteristics of
      bureaucracy; compensating for bureaucracy on behalf of the health care team; and
      providing leadership which ensured effective care from others. All constituted
      invaluable yet obscured and unrecognized components of nursing's indirect
      contribution to patient care. The costs to keeping this work 'secret' were
      readily apparent. The understanding derived from this research affords new
      insights into why nursing has kept this hidden work secret. These insights, in
      turn, help identify potential solutions for consideration by all concerned about
      nursing's professional role, status and identity.

PMID- 8138620
TI  - Caring in nursing education: an analysis.
AB  - Caring has been cited by many authors as the core value of nurse educator-student
      relationships. Others have discussed the need for caring to be translated and
      transmitted in the practices of nursing education. However, a clear
      conceptualization of what caring in nursing education is and how it is
      transmitted to students does not yet exist. The following is an exploration of
      the concept of caring in nursing education as it is revealed in nursing research
      and literature. The authors present a critical analysis of the definitions,
      objectives, attributes and constraints of caring in nursing education. What is
      currently known and perceived about caring in nursing education, as well as what
      is not known and what needs to be known, is highlighted. Imperatives for future
      research are identified.

PMID- 8138621
TI  - Making research useful to the practising nurse.
AB  - This paper examines the problem of developing research in nursing and the
      challenge of establishing its relevance and usefulness to the practising nurse.
      It is accepted that considerable progress has been made worldwide in recent years
      in the development of nursing research but nurses remain generally remote from
      the intellectual challenge of an evolving research-based profession. The
      publication of research reports is examined in the light of the acknowledged need
      for dissemination of research findings and differences in their presentation are
      noted as evidence of an apparent discouragement of the practising nurse from
      sharing in the accumulated nursing knowledge through research. It is argued that
      learning about research should be brought into the centre of basic nursing
      education and the growth in clinical research should be encouraged as a means of
      demonstrating the usefulness of research to the practising nurse.

PMID- 8138622
TI  - The Delphi technique: a methodological discussion.
AB  - As in nursing, recent curriculum reform in radiographer education has resulted in
      the development of undergraduate programmes, and a study referred to in this
      paper investigated the activities of supervising radiographers in support of the
      undergraduate curriculum. Following on from 'ward learning environments' research
      in nursing, the most important activities which assist radiography students'
      clinical learning were investigated by means of the Delphi technique. At the
      design stage, a deficiency in previous work using the technique was identified,
      in that decisions relating to consensus among research respondents appeared to be
      based on arbitrary or post hoc rationales rather than predetermined or objective
      criteria. As the Delphi technique is being increasingly employed in nursing and
      similar research, it is important to explore issues of consensus, validity and
      reliability. The paper makes recommendations for improving these aspects in
      future studies.

PMID- 8138623
TI  - The curriculum revolution: can educational reform take place without a revolution
      in practice?
AB  - Nursing scholars from around the world have written extensively in the past
      decade of the need to transform current health care systems and of the role of
      nursing education in achieving this goal. Proposals for change abound in the
      literature and are beginning to emerge in practice but not without difficulties.
      Having examined new curricular developments, this paper will discuss barriers to
      further progress. It is suggested that emphasis on reforming schools of nursing
      and teaching practices has tended to overlook broader institutional influences,
      in particular the clinical settings in which 50% of nurse education occurs. This
      paper will outline the major themes of the curriculum revolution, examine the
      ways in which educational institutions, health care settings and nursing
      organizations hinder the progress of curricular reform, and discuss possible
      solutions and their limitations.

PMID- 8138624
TI  - Selecting clinical preceptors for basic baccalaureate nursing students: a
      critical issue in clinical teaching.
AB  - The concept of preceptorship in baccalaureate nursing education continues to be
      endorsed as a viable alternative clinical teaching strategy. However there
      remains a dearth of research to substantiate many of those benefits vis-a-vis
      preceptor, preceptee and ultimately the health care consumer. Moreover, there are
      minimal substantive data regarding the criteria which are required for the actual
      selection of the clinical preceptor. Not infrequently, preceptors are selected
      primarily for their availability during the clinical placement of students. As a
      result, baccalaureate nursing students are being preceptored by staff nurses with
      little or no preparation for assuming a role in which they are expected to
      promote the principles and ideology of baccalaureate nursing education. Is this
      fair to the preceptor, preceptee and the client? Can it be said that the nursing
      faculty, in promoting such a process, are in fact promoting the status quo?

PMID- 8138625
TI  - Implantable devices for venous access: nurses' and patients' evaluation of three
      different port systems.
AB  - Implantable injection port systems are safe and convenient for long-term venous
      access. The present investigation comprises nurses' and patients' evaluation of
      three different types of devices; Port-A-Cath (16.0 g), Cordis Miniport (3.8 g)
      for implantation in the chest wall and the PAS Port system (5.6 g) for
      implantation in the forearm. The devices were implanted for chemotherapy. Eighty
      patients and 17 nurses answered a questionnaire regarding their experience with
      the devices. Overall, the systems functioned well and were helpful for both
      patients and nurses. In the patient study few significant differences emerged.
      Nurses noted that the PAS Port system was more difficult to withdraw blood from
      (P < 0.001) and its infusion flow capacity was inferior to the two ports in the
      chest wall (P < 0.001). Port-A-Cath was judged to be the easiest system for
      needle insertion and the needle position was felt to be more secure (P < 0.001).
      Fourteen of the 17 nurses preferred Cordis Miniport for cosmetic reasons (P <
      0.001). All devices functioned well. The differences in shape, size and site of
      implantation allow an optimum port selection for each patient. The replies in
      this study expressed the need for educational programmes in order to spread the
      injection port concept further.

PMID- 8138626
TI  - An argument against the use of the concept of 'persons' in health care ethics.
AB  - This paper discusses the use of the concept of 'persons', and its related
      principle 'respect for persons', in health care ethics. It is suggested that the
      main use of the concept is in attempts to answer the questions: 'Who owes moral
      respect?' and 'To whom is it owed?'. An examination of different writers and
      their use of the concept of 'persons' show it to be unsuccessful in answering the
      first question, and dangerous and unacceptable in answering the second.
      Therefore, it is suggested the concept should not be used at all in health care
      ethics. An alternative idea is suggested, based on the work of Hursthouse (1992).

PMID- 8138627
TI  - Vertical transmission in HIV infection/AIDS: a feminist perspective.
AB  - HIV infection and AIDS create a unique dilemma for women in their potential for
      vertical transmission of these conditions. Selected feminist perspectives in
      ontology, epistemology, and axiology are reviewed to illuminate possible social,
      cultural, and political circumstances of these women. Drawing both on these
      perspectives and various sources of data about women with HIV/AIDS, some
      implications for nursing complete this discussion.

PMID- 8138628
TI  - Gift Exchange Theory: a critique in relation to organ transplantation.
AB  - Organ transplantation is becoming more important as a viable method of treatment
      for certain severe medical conditions. It is a complex and demanding process for
      all involved. Nursing as a developing science must respond to cultural and
      economic changes. Therefore, a need exists to develop a body of empirically based
      knowledge to understand and support the process of organ transplantation. This
      paper will argue that as trading in organs is unacceptable to the moral standards
      of western society and outlawed in many countries, an alternative framework must
      be considered for understanding the mechanisms through which organs are donated
      and utilized. The donating and receiving of organs may be equated with gift
      giving, as there is no barter of commodities involved. Therefore, a useful
      framework to explore this phenomenon will be one that underpins the process of
      giving and receiving of gifts. Gift Exchange Theory will be evaluated and
      critically examined in relation to organ transplantation and the role of nurses
      in this process.

PMID- 8138629
TI  - Paediatric day surgery: day-case unit admission compared with general paediatric
      ward admission.
AB  - A small exploratory study (n = 20) is described which compares the experience of
      children admitted to a day-case unit with that of children admitted to a general
      paediatric ward. Both samples received inadequate amounts of information,
      particularly prior to discharge. The care offered in the day-case unit was found
      to be woefully deficient in many areas and the wisdom of utilizing occasional
      sessions in an adult day-case unit is questioned. The crucial role of skilled
      nurses trained in the care of sick children is emphasized.

PMID- 8138630
TI  - An evaluative study of a community health service development.
AB  - This paper describes a research study designed to evaluate a community health
      service development in one health authority in rural England. The study compared
      two types of primary care teams working towards the same objectives. Surveys of
      patients and staff in the health authority were conducted about a range of
      issues, defined by the original aims of the scheme. Measures were made of care
      received by people over 75 years of age, consumer satisfaction, staff experiences
      of the multi-disciplinary team, job satisfaction and liaison with social services
      personnel. Few differences existed between the two forms of care on all of these
      measures. This paper contains a discussion of the findings alongside an
      examination of the implications for future health service developments,
      particularly flagship enterprises such as nursing development units. The
      importance of well established baseline measurements is emphasized by both the
      research findings and the discussion.

PMID- 8138631
TI  - Nurses' role in informing breast cancer patients: a comparison between patients'
      and nurses' opinions.
AB  - The present study was conducted to determine which nursing care activities in
      informing breast cancer patients are considered important by the patients
      themselves and their nurses. One hundred and nine breast-operated women and 125
      nurses participated in the study. All patients had contracted breast cancer in
      the previous 3 years but not within the previous 3 months. Ward and clinical
      nurses from one university and six area hospitals were contacted. The patients
      considered that the information that they had received and their level of
      knowledge of their own situation was not conducive to good recovery. The nurses'
      opinions were in agreement, although their overall assessment of the situation
      was more positive.

PMID- 8138632
TI  - Effect of the use of sleep medication in Dutch hospitals on the use of sleep
      medication at home.
AB  - Insomnia is an important nursing problem in hospitals. Although the use of sleep
      medication is often criticized, it is one of the commonest interventions with
      regard to sleep problems. In this study, the effect of the administration of
      sleep medication in Dutch hospitals on the use of sleep medication at home is
      investigated. Only patients were included who had never used sleep medication
      before admittance in hospital. Results show that patients who used sleep
      medication for at least 5 days in hospital (n = 233) used sleep medication more
      often at home after discharge than patients who did not use sleep medication in
      hospital (n = 55). Furthermore, the study showed that those patients who used at
      least 5 days' sleep medication, especially those patients who used sleep
      medication more often in hospital, also used sleep medication more often at home.
      This is in line with the addictive effects of sleep medication. From these
      results it can be concluded that the administration of sleep medication is not
      without danger. Therefore, it is recommended to search for alternative
      interventions, especially for patients who are in hospital for a longer period.

PMID- 8138633
TI  - Dehydration: burden or benefit to the dying patient?
AB  - Significant numbers of patients die each year from malignant disease. The
      question of whether or not to administer artificial hydration therapy to the
      patient who is in the last few days of life has been discussed for some time.
      Some health care professionals contend that a reduced fluid intake, which often
      accompanies the dying process, may result in a potentially painful and
      distressing state of dehydration, requiring preventative measures of fluid
      replacement therapy. In contrast, other clinicians suggest that artificial
      hydration is often of no proven benefit in the context of the dying and may
      impose additional physical and psychological burdens on the patient. This paper
      investigates the advantages and disadvantages of artificial hydration therapies
      in terms of the symptom distress experienced by the terminally ill cancer
      patient. Its aim is to promote discussion about this vital aspect of patient
      care.

PMID- 8138634
TI  - Risk taking and its influence on metabolic control: a study of adult clients with
      diabetes.
AB  - Clients afflicted with diabetes are routinely faced with making decisions about
      insulin control, diet, exercise and skin care. The specific aims of this study
      were (a) to determine if clients with controlled blood sugar levels were more
      likely to have risk-averse information processing styles and, (b) to determine
      the extent to which the differences in blood sugar levels were attributed to
      information processing styles, after controlling for knowledge of diabetes,
      participation in home monitoring, and age. A comparative design utilizing 86
      insulin-dependent male and female clients with diabetes was used. Findings
      indicated that there were no differences in risk scores between uncontrolled and
      controlled diabetics. Additionally, in this study there were no differences in
      control between clients who were knowledgeable and those who were not. This study
      has several implications for nursing practice. As taking risks may not be as
      dangerous to the diabetic client's wellbeing as many believe, there may be a need
      to consider this behaviour in developing the client's plan of care. Questions are
      also raised about the influence of knowledge on control.

PMID- 8138635
TI  - Visiting hospitalized patients.
AB  - Visiting policies in acute care institutions affect patients and families. The
      study sought to answer these questions: What are current hospital visiting
      policies and accompanying provisions for families? How are nurses implementing
      these policies? A questionnaire was developed, and reliability and content
      validity were established. The questionnaire was mailed to a randomly selected,
      stratified sample of 125 approved hospitals in 10 US states, with a 40% return
      rate. Consent and anonymity were explained in an accompanying covering letter.
      Results indicated that there was a wide range of general hospital visiting hours.
      Limitations on general visiting hours were primarily due to hospital policy (age,
      children, number of visitors) and nursing judgement (visitor illness, length of
      visit). General visiting hours and intensive care area visiting hours for
      paediatric patients were more extensive than for adult patients. Factors which
      influenced exceptions to visitation policies in intensive care areas focused on
      patient acuity and patient needs. Recovery room visiting was limited. If the
      patient was in a private room, visiting hours and provisions for family members
      were extensive. Provisions for family members of intensive care patients were
      minimal. Nursing judgement significantly influenced implementation of visitation
      policies.

PMID- 8138636
TI  - The role of lavender oil in relieving perineal discomfort following childbirth: a
      blind randomized clinical trial.
AB  - Aromatherapy is a movement growth in popularity, but lacking scientific
      justification in the field of practice, although laboratory experiments are in
      evidence. Lavender oil is frequently selected for aromatherapy as having
      antiseptic and healing properties. More specifically, it has been used as a bath
      additive postnatally to reduce perineal discomfort. A blind randomized clinical
      trial is described, involving three groups of mothers, one using pure lavender
      oil, one a synthetic lavender oil and one an inert substance as a bath additive
      for 10 days following normal childbirth. Analysis of daily discomfort scores
      revealed no statistically significant difference between groups. It cannot be
      concluded that current practice results in a reduction of postnatal perineal
      discomfort at the dilution levels used. However, there is some consistency in
      results between the 3rd and 5th days, with those women using lavender oil as a
      bath additive recording lower mean discomfort scores. This is a time when the
      mother usually finds herself discharged home and perineal discomfort is high. A
      total of 635 women participated and no side-effects were found.

PMID- 8138637
TI  - Cardiopulmonary resuscitation decision making in long-term care: a role for the
      nurse?
AB  - In many long-term care settings, cardiopulmonary resuscitation (CPR) is regarded
      as an available treatment option. However, for the majority of long-term care
      residents the expected outcome following CPR is poor. This descriptive study
      explored the CPR decision-making process in two long-term care institutions. This
      was accomplished through the administration of questionnaires to nursing staff,
      residents, residents' family members and through completion of a chart review of
      deceased individuals. This paper primarily addresses the role of nurses in the
      CPR decision-making process in long-term care. Nurses were rarely explicitly
      involved in the CPR decision-making process. Knowledge deficits of nurses
      concerning the CPR policy at the institutions and the expected outcomes of CPR
      were identified. Also noted were inconsistencies between policy and practice,
      with CPR being withheld in practice more often than dictated by protocol.
      Strategies to facilitate the CPR decision-making process in long-term care
      settings are suggested, and specific roles for nurses in relation to CPR decision
      making are presented.

PMID- 8138638
TI  - Physician sexual exploitation: Wisconsin in the 1980s.
AB  - Several factors make 1980s Wisconsin a useful window on the social changes now
      shaping the response by psychiatry and other medical specialties to patients who
      accuse physicians of sexual misconduct. The state medical board disciplined 19
      such physicians in the 1980s, in contrast to 1 each in the two prior decades, as
      the state weathered several highly publicized cases in which multiple
      complainants accused prominent psychiatrists. Wisconsin was one of the first
      states to enact criminalization (1984) and mandatory reporting (1988) laws. Also,
      the relatively high number of physicians (3% of the state's psychiatrists)
      disciplined in the 1980s allows a beginning look at the epidemiology of this
      problem. Several patterns emerged: 1) Lone complainants who are psychiatric
      patients face many pressures. Fewer than 25% of successful cases against
      psychiatrists involved a lone complainant, while all the nonpsychiatrists were
      disciplined on the basis of a single patient's complaint. 2) More than half of
      disciplined psychiatrists had regained licensure by decade's end. Neither
      multiple sexual complainants nor multiple types of complaints seemed to deter
      relicensure. However, no physician with a criminal conviction has been
      relicensed. 3) Surprisingly, several connections were noted among offenders,
      including mentorships, friendships, and therapy relationships. Three disciplined
      psychiatrists were past presidents of local psychiatric societies. Psychiatrists
      who had been disciplined were significantly more likely to have been trained
      under one of the eminent sexual abusers than were other male psychiatrists in the
      state.

PMID- 8138639
TI  - More on Bosnian rapes.

PMID- 8138641
TI  - Complementary medicine.

PMID- 8138640
TI  - More on Bosnian rapes.

PMID- 8138642
TI  - Eating disorder history in women with obsessive compulsive disorder.
AB  - This study examined the frequency of eating disorders in women with obsessive
      compulsive disorder (OCD). Letters were sent to area psychiatrists asking them to
      refer patients diagnosed with OCD to a research study. Subjects completed the
      Yale Brown Obsessive Compulsive Scale and a survey including history of eating
      disorders. Thirty-one women participated in the study. Forty-two percent (N = 13)
      had a past or current history of an eating disorder: 26% anorexia nervosa alone
      (N = 8); 3% bulimia nervosa alone (N = 1); and 13% both anorexia and bulimia (N =
      4). Our study found a higher percentage of history of eating disorders than
      expected. Perhaps specifically asking about history of weight loss, binging, and
      vomiting allowed for fuller disclosure of eating disorders than other studies
      that relied on retrospective chart review or limited the survey to current eating
      symptoms. A past history of eating disorder may be more common than previously
      believed and may frequently precede the diagnosis of OCD.

PMID- 8138643
TI  - One voice on menopause.

PMID- 8138644
TI  - Shattering medicine's glass ceiling.

PMID- 8138645
TI  - Independence or subservience--choice is ours.

PMID- 8138646
TI  - The biology of addiction.

PMID- 8138647
TI  - Difficulties in the management of superior vena caval obstruction in young
      adults.
AB  - Case records of 50 patients of superior vena caval obstruction in young adults
      treated and followed-up at Radiotherapy Department, Medical College Hospitals,
      Calcutta have been looked into. Twenty-eight out of these 50 patients had disease
      confined to mediastinum only during presentation. In consideration of the fact
      that the optimum management of superior vena caval obstruction depends upon a
      balance between just adequate pretreatment investigation and early institution of
      treatment, the various difficulties in the management discussed. With the
      existing infrastructural facilities, the institutional policy for the management
      of superior vena caval obstruction in young adults whose disease is confined to
      mediastinum only, during presentation, is described.

PMID- 8138648
TI  - Hepatitis B vaccination and the rate of seroconversion in high risk contacts.
AB  - Twenty-seven employees of a blood transfusion centre, Calcutta were vaccinated
      with hepatitis B vaccine (recombinant DNA technology), 20 micrograms/1 ml
      intramuscularly on 0, 8, 32 weeks interval. The seroconversion rate at 8, 32, 40
      weeks were 29.6%, 55.5% and 100% respectively. The recombinant hepatitis B
      vaccine is acceptable and safe. The seroconversion rate is comparable to plasma
      derived hepatitis B vaccine.

PMID- 8138649
TI  - Omphalitis neonatorum.
AB  - Clinicobacteriological profile of omphalitis neonatorum was analysed in this
      prospective study which comprised 4776 neonates (4410 hospital-born, 366
      deliveries at home). The incidence of omphalitis in the hospital-born babies was
      2.3%. About 21.3% babies delivered at home were admitted for neonatal sepsis,
      meningitis, birth asphyxia, etc. They were found to be concomitantly suffering
      from omphalitis. Improper severing of the umbilical cord, application of oily
      substances on the umbilical stump and unhygienic rearing practices during
      neonatal period were some of the important predisposing factors. The fall of the
      umbilical stump and the diagnosis of omphalitis neonatorum was made significantly
      earlier (p < 0.001) in the hospital-born babies and none of them developed
      sepsis. The institution of therapy for umbilical sepsis was considerably delayed
      in the babies delivered at home and the omphalitis was the probable cause of
      sepsis in 46.6% cases. The Gram-negative organisms were responsible for
      omphalitis in 57.1% cases. Klebsiella was the commonest Gram-negative organism.
      Its incidence was more among the babies delivered at home signifying a
      potentially infective environment in the community. Gram's stain was a reliable
      and easy method for grossly identifying the organism in the umbilical smear.

PMID- 8138650
TI  - Profile of women undergoing medical termination of pregnancy in hospital.
AB  - The present study was undertaken to find out the profile of women undergoing
      medical termination of pregnancy (MTP) in Hospital, 1000 consecutive cases
      undergoing MTP at RG Kar Medical College and Hospital were studied. 95.6% cases
      were married and 4.4% cases were unmarried. In the whole series, 7.6% cases were
      teenagers though in unmarried group 90.9% cases were teenagers. In 56% of married
      group the monthly family income was more than Rs 500/- whereas majority in
      unmarried group had family income less than Rs 500/- per month. In the whole
      series, 44.4% cases were illiterate, 48.2% cases were educated up to primary
      school and only 7.3% cases up to high school and above. In the married group, 204
      cases undergoing MTP with one living issue, 388 cases with 2 living issues and
      396 cases with 3 living issues. In the whole series, 88% cases were 1st trimester
      MTP and 12% were 2nd trimester MTP cases, whereas in the unmarried group 72.7%
      cases were in the 2nd trimester, and 5.7% cases had history of previous MTP.
      Effective contraception was only 6% before MTP whereas it increased to 90.6%
      after MTP.

PMID- 8138651
TI  - Comparative evaluation of intramuscular buprenorphine, pentazocine and nefopam in
      post-operative pain relief.
AB  - In immediate postoperative period, many injectable analgesics are being used with
      diverse side effects. The present study was conducted on 75 patients of both
      sexes, who underwent various types of surgery, to evaluate pain relief in
      immediate postoperative period. The drugs used for producing postoperative
      analgesia are buprenorphine, pentazocine and nefopam, all by intramuscular route.

PMID- 8138652
TI  - Postfebrile depressive reaction in children.
AB  - Seventy-nine cases of one specific type of depressive reaction in children who
      had mild fever during or just prior to the episode of depression were studied
      during a period of 16 years between 1968 and 1984. Comparison of the observed
      group with the control groups established the specificity of the episode
      depression with only one type of fever which was most probably of viral origin.

PMID- 8138653
TI  - Amnesia following thalamic haemorrhage.

PMID- 8138654
TI  - Medical examination, certification and informed consent.

PMID- 8138655
TI  - Dunkel proposals and the medical profession.

PMID- 8138656
TI  - Conventional operation versus keyhole surgery.

PMID- 8138657
TI  - Medical liability--international scene.

PMID- 8138658
TI  - Suggestions to medical profession to fight against CPA.

PMID- 8138659
TI  - MCA serum determination in breast carcinoma patients for the diagnosis of bone
      metastases.
AB  - Serum MCA levels were determined in 173 consecutive patients with breast cancer
      in order to assess the clinical utility of MCA for the detection of bone
      metastases. Bone pathology was diagnosed by scintigraphy, radiology and clinical
      follow-up. Metastases were found in 37 patients, benign lesions in 25, and in 111
      no bone lesions were found. Eighteen of the 173 bone scans were considered
      indeterminate for metastases. Based on the receiver-operating characteristic
      curves (ROC) analysis, the cut-off level for MCA was set at 20 U/ml. Only in 4 of
      the 37 patients with bone metastases MCA was below 20 U/ml. All 4 patients had
      completed their chemotherapy course within six months before MCA determination.
      Only in 6 patients of the 136 without bone metastases MCA levels were above 20
      U/ml. Of the 18 patients with indeterminate bone scans, 15 had benign lesions and
      all of them had MCA levels below 20 U/ml. MCA determination is a sensitive method
      for the detection of bone metastases in breast carcinoma. We encourage the use of
      this procedure for the selection of high-risk groups or as a complementary method
      for the interpretation of bone scintigraphy.

PMID- 8138660
TI  - CA 15.3 with urinary calcium excretion is useful in the diagnosis and monitoring
      of bone metastases from breast cancer.
AB  - Serum levels of breast carcinoma antigen (CA 15.3) and urinary calcium excretion
      (UCa) were determined in 73 patients with breast cancer: 36 without bone
      metastases (stage I-IV) and 37 with bone metastases. The patients in the latter
      group were further investigated at 2, 4 and 6 months from the start of treatment.
      Both markers showed significant elevations in the group with bone metastases (CA
      15.3: P = 1.0 x 10(-6), UCa: P = 8.6 x 10(-9)). The bone metastasis index (BMI),
      which represents the combination of the markers, had better diagnostic efficacy
      (90%) than CA 15.3 alone (84%) or UCa alone (82%). During treatment of bone
      metastasis, the longitudinal levels of the markers showed a highly significant
      association with the therapeutic response assessed by the UICC criteria. For
      identifying progression of disease, the diagnostic efficacy of CA 15.3, UCa and a
      combination of both, the so-called Biochemical Index of Response (BIR), was 65%,
      70% and 79%, respectively, at two months and 89%, 84% and 92% at four months.
      Application of the tandem, CA 15.3 with UCa, was very useful for the detection of
      bone metastases and the prediction of response to therapy.

PMID- 8138661
TI  - Serum and tissue levels of CEA, TPA, CA 125 and CA 15.3 in patients with lung
      cancer.
AB  - Forty-nine healthy subjects (Group I), 24 patients with benign lung diseases
      (Group II) and 48 patients surgically treated for lung cancer (Group III): 28
      with squamous cell carcinoma (SCC) and 20 with adenocarcinoma (adenoca), were
      tested for the presence of carcinoembryonic antigen (CEA), tissue polypeptide
      antigen (TPA), cancer antigen CA 125 and antigen CA 15.3. The four markers were
      measured in the serum of the patients of the three groups and in the cytosol
      extract of tumoral and peritumoral tissues of Group III subjects. The mean levels
      of serum CEA and TPA were significantly higher in squamous cell carcinoma and in
      adenocarcinoma patients than in normal subjects. In benign lung disease serum CEA
      was equal and TPA slightly higher than in normal subjects. CA 125 was higher in
      the serum of patients with malignant diseases compared to normal or benign lung
      diseases but this difference was not statistically significant. Serum CA 15.3
      levels were similar in all subjects studied. CA 125 in squamous cell carcinoma
      cytosol was much higher than in peritumoral cytosol whereas the other three
      markers were not significantly different in tumor cytosol or peritumoral cytosol.
      A direct correlation between serum and cytosol values was observed for CEA, but
      not for the other markers. The levels of the four markers in serum and cytosol
      did not correlate with the stage or grade of the tumors.

PMID- 8138662
TI  - Modification of soluble immunological parameters during treatment with
      interleukin-2.
AB  - In the present study we tested numerous soluble immunological parameters (soluble
      Interleukin 2 receptor, Beta 2 microglobulin, Neopterin, soluble CD8 antigen,
      gamma Interferon and alpha Tumor Necrosis Factor) in sera obtained from 18
      advanced cancer patients during subcutaneous treatment with recombinant
      Interleukin 2. The treatment cycles consisted of a dose of 9 x 10(6) IU/m2 twice
      daily for 2 days followed by 1.8 x 10(6) IU/m2 twice daily for 5 days/week during
      6 weeks. Even before therapy, neoplastic patients had higher levels of soluble
      Interleukin 2 receptor than a group of healthy subjects. Moreover, basal soluble
      CD8 antigen levels showed significant differences (p < 0.01) in patients with
      different clinical responses (responders and non-responders). During treatment we
      observed a fast increase (in the first or second week) of all parameters
      considered; soluble Interleukin 2 receptor and soluble CD8 antigen were the
      markers that were best related to the course of immunotherapy. In conclusion,
      monitoring recombinant Interleukin 2 immunotherapy with immunological parameters
      in serum seems to be of interest. However, more data are necessary to confirm the
      real value of the single markers.

PMID- 8138664
TI  - Tumor markers in the blood of preoperative digestive cancer patients.

PMID- 8138663
TI  - Immunohistochemical detection of carcinoembryonic antigen (CEA) in non-neoplastic
      lung disease.
AB  - Carcinoembryonic antigen (CEA), though typically associated with malignant
      epithelial neoplasms, is known to be present at elevated levels even in the serum
      of normal individuals and of patients suffering from interstitial diseases of the
      lung. Few reports have addressed the question of the possible source of CEA
      immunoreactivity within the lung parenchyma. Two patients with elevated CEA serum
      levels were studied by immunohistochemistry on open lung biopsy specimens. Two
      different antibodies (one absorbed with non-specific cross-reacting antigen, NCA)
      were used. The results show that bronchiolar cells and type II pneumocytes are
      focally positive with both antibodies; the immunoreaction is preserved even after
      absorption with NCA. In agreement with experimental data on CEA synthesis in
      fetal bronchial cell lines, these findings indicate that interstitial lung
      disorders may induce abnormal CEA-like substance expression. In these cases,
      where no epithelial neoplasms subsequently develop, the cutoff level for CEA in
      serum should be raised. Bronchiolar and alveolar cells appear primarily
      responsible for CEA-like substance production.

PMID- 8138665
TI  - Placental serum alkaline phosphatase, defined by monoclonal antibody C2, in non
      malignant diseases and in non-germinal tumors.

PMID- 8138666
TI  - [Epidemiological study on respiratory syncytial virus lower respiratory tract
      infections in northern Hokkaido, Japan].
AB  - We carried out an epidemiological study on lower respiratory tract infections,
      concerning the respiratory syncytial virus (RSV) infection, in northern Hokkaido,
      Japan, during the 2-year-study period from April 1991 to March 1993. There were
      467 hospitalized patients with lower respiratory tract infections. We examined
      the presence of RSV antigen in their nasopharyngeal specimens of 456 out of 467
      patients (97.6%) by enzyme immunoassay. The diagnosis of Mycoplasma pneumoniae
      infection was done by the rise of antibody titer, performed with complement
      fixation method, in the sera of the acute and convalescent phases. There were 133
      patients with RSV infection (28.9%), 45 patients with Mycoplasma pneumoniae
      infection (9.8%) and 7 patients with measles virus infection (1.5%). RSV played
      an important role in the lower respiratory tract infections in northern Hokkaido,
      Japan. The epidemic of RSV infection was observed in spring and early winter in
      1991 and only in early winter in 1992. The number of patients with RSV infection
      from April 1991 to March 1992 was greater than that from April 1992 to March
      1993. In contrast with RSV infection, the epidemic of Mycoplasma pneumoniae
      infection was observed in 1992. We speculated that the RSV and Mycoplasma
      pneumoniae infections might interfere with each other.

PMID- 8138667
TI  - [Investigation of Chlamydia trachomatis-specific IgA, IgG antibody with EIA
      method].
AB  - Recently, two new kits, HITAZYME (Hitachi Chemical Co., Ltd.) and SERO IPALISA
      (Savyon Diagnostics, Ltd.), for the assay of anti-C. trachomatis antibodies by
      the enzyme immunoassay (EIA) method have been developed and put into clinical
      application. In the study reported here, the authors investigated the clinical
      usefulness of these assay kits, together with the IPAzyme and micro-IF test, in
      the diagnosis of cases of urogenital tract C. trachomatis infections. 1. The
      positive rates for IgA antibodies, which are considered to be an indicator of
      active infection, obtained with the HITAZYME and SERO IPALISA kits in the 82
      antigen-positive cases were significantly (p < 0.005) higher than the rates
      obtained with the IPAzyme and micro-IF test. These results showed the usefulness
      of the HITAZYME and SERO IPALISA kits for detecting C. trachomatis infections. 2.
      A comparison was made of the assay results obtained with the HITAZYME and SERO
      IPALISA kits, and it was found that there was a large number of cases (142) that
      tested negative for IgA antibodies with the HITAZYME but positive with the SERO
      IPALISA kit. We carried out a confirmatory test on the specimens of cases for
      which the results obtained with the HITAZYME and SERO IPALISA kits were not in
      agreement. This test employed the Western blotting method using COMC (the antigen
      extracted from EB of C. trachomatis strain L2 and used in the HITAZYME kit) and
      whole EB of C. trachomatis strain L2 (the antigen used in the SERO IPALISA kit).
      The results showed a significantly higher degree of agreement between the
      HITAZYME kit data and the Western blotting data than between the SERO IPALISA kit
      data and the Western blotting data. 3. In addition, with the objective of
      investigating the existence of cross reactivity with anti-C. pneumoniae
      antibodies, we performed Western blotting using as the antigen crude whole EB of
      C. pneumoniae strain TW-183. The results showed that anti-C. pneumoniae
      antibodies were detected in 25 of 35 (71.4%) cases that were negative with C.
      trachomatis antigen and the HITAZYME kit and positive with the SERO IPALISA kit.
      These findings indicate a strong possibility that these cases positive with the
      SERO IPALISA kit are due to a cross reaction with anti-C. pneumoniae
      antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8138668
TI  - [Clinical study on acute bronchitis using inflammatory cytology of sputum].
AB  - During fifteen months between January 1989 and March 1990, 137 episodes (136
      cases) of acute bronchitis were clinically examined in Iki Public Hospital. From
      the results of quantitative sputum culture in 99 episodes, 58 episodes (56.8%)
      had obviously bacterial infections. The three major causative bacteria were H.
      influenzae (45.7%), S. pneumoniae (27.1%) and B. catarrhalis (17.2%).
      Inflammatory cytology of the sputum revealed that in the patients with acute
      bronchitis macrophage, vivid neutrophils and bronchial epithelial cells were
      clearly observed, while in the patients of chronic respiratory infections those
      cells were fewer in number. Before and after therapy, respiratory functions and
      blood gas were evaluated in 45 cases. Significant improvements were observed in
      PaO2, FEV1.0, etc. During eight years from 1982 to 1989, B. catarrhalis has been
      gradually increasing, as one of major causative organisms. Each year, the rate of
      bacterial infection was approximately fifty percent in acute bronchitis.

PMID- 8138669
TI  - [Clinical study on ivermectin against 125 strongyloidiasis patients].
AB  - We treated 125 patients with strongyloidiasis (78 males and 47 females) by 2 oral
      doses of ivermectin (6 mg) at 2-week interval, and obtained the following
      results: 1. Eradication rate after treatment was 86.4% (108 of 125 patients),
      responsively. Out of the total 17 patients were resistant (non-responsive) to
      treatment, 8 patients received a further course of ivermectin and all
      Strongyloides stercoralis in their feces were eradicated. 2. Side effects were
      observed in 7.2% of the patients after the first dose treatment and in 3.2% after
      the second dose. But all symptoms were mild and self-limited. Although liver
      disfunction developed in 13.6% of the patients, no symptoms occurred and no
      special treatment was required. 3. Positive rate of anti-HTLV-I antibody in the
      resistant group was significantly higher (80.0%) than in the eradicated group
      (29.2%) and in the stool-negative group (0%). 4. Although eosinophils before
      treatment in the eradicated group was significantly higher than that of controls,
      there was no significant difference between the resistant group and controls. IgE
      levels in the resistant group was significantly lower than in the eradicated
      group. We would like to conclude that IVM is the best drug for treatment of the
      patient with Strongyloides stercoralis not only from this results but also our
      previous reports which had investigated the clinical efficacy on thiabendazole,
      mebendazole and albendazole.

PMID- 8138670
TI  - Bacterial biofilm in chronic airway infection.
AB  - We hypothesized that bacterial biofilm formation could be an important factor
      that makes some infections intractable, and conducted the following study to
      confirm the role of bacterial biofilm in airway infection. We first
      microscopically examined airway surface in patients with an intractable airway
      infection and detected bacterial biofilms adhering to the airway surface. Most of
      the airway biofilm diseases were diffuse panbronchiolitis and bronchiectasia due
      to Pseudomonas aeruginosa or Klebsiella pneumoniae. In vivo examination revealed
      that chemotaxis of neutrophils in patients with biofilm bacteria was less than
      that in patients with floating type bacteria. Interaction of Pseudomonas biofilm
      with antibacterial agents was examined in vitro. The rate of survival of biofilm
      bacteria was higher than that of floating bacteria in contact with twice the
      minimal bactericidal concentration of ciprofloxacin (CPFX) or two to 10 times the
      minimal inhibitory concentration of cefclidin and meropenem which are highly
      potent antibacterial agents against P. aeruginosa. Additionally, the effects of
      clarithromycin (CAM) on biofilm bacteria were studied in order to investigate new
      therapeutic maneuvers against a bacterial biofilm. Also, the combination of CPFX
      and CAM was more effective in decreasing the bacterial survival rate than CPFX
      alone. The results suggest that administration CAM can be one of the therapeutic
      maneuvers against biofilm bacteria.

PMID- 8138671
TI  - [A case of mefloquine-resistant Plasmodium falciparum malaria with convulsion
      after antimalarial treatment].
AB  - We report a case of 40-year-old with chloroquine- and mefloquine-resistant
      Plasmodium falciparum. He had a single grand mal seizure 37 days following
      retreatment with quinine intravenously, which resulted in rapid clearance of
      fever and parasitemia, in addition to mefloquine. He had a long history of
      seizures, which were well controlled by phenytoin. Because he has never had such
      a seizure before and computerized tomographic scanning of the brain after
      admission showed no abnormal findings which caused convulsions, it seemed to be
      an adverse reaction caused by antimalarial drugs. It is possible that a double or
      triple combination treatment for the emergence of multiresistant falciparum
      malaria might more frequently produce severe side effects, such as psychiatric
      reactions and convulsions. This case suggests that physicians must have a long
      follow-up period for chronic toxicity of antimalarial drugs, especially after
      using drug combinations for falciparum malaria.

PMID- 8138672
TI  - Successful treatment of severe odontogenic infections which caused septicemia.

PMID- 8138673
TI  - [A case of cardiogenic shock caused by Vibrio parahaemolyticus].
AB  - A case of a 53 year old healthy female complaining of diarrhea and abdominal pain
      after taking raw fish is presented. She immediately went into shock and
      unconsciousness. Central venous pressure was 8 cmH2O and her ECG showed a first
      degree AV block and ST-T changes in almost all leads. After mechanical
      ventilation and administration of dopamine, dobutamine, cefotiam, ciprofloxacin,
      she became alert and recovered from her critical condition. V. parahaemolyticus
      which produces thermostable direct hemolysin (TDH) was cultured from the feces on
      admission. Kanagawa phenomenon was positive. Arterial blood culture was negative
      and the titer of serum endotoxin was low. The diagnosis of cardiogenic shock due
      to exotoxin produced by V. parahaemolyticus was made. Serological examination by
      ELISA showed elevation of IgG class antibody against TDH and TRH (TDH related
      hemolysin). And antibody against TDH was normalized after 180 days. By review of
      literature, there are some case reports of cardiogenic shock complicated with V.
      parahaemolyticus infection, but few showed elevation of antibody against TDH and
      TRH in the serum of the survived patient.

PMID- 8138674
TI  - [Prevalence of Borrelia on tick collected in Yamanashi Prefecture].

PMID- 8138675
TI  - [Flora in the anterior nares of patients in the neurologic ward: the influence of
      nasogastric intubation and mechanical ventilation].
AB  - MRSA has been isolated frequently from patients in the neurologic ward of Minami
      Okayama Hospital. We examined the flora in the anterior nares of 37 patients in
      the neurologic ward and 36 patients in the medical ward. Existence of dysphagia
      and nasogastric intubation is considered to make a marked difference between
      nasal flora of neurologic patients and that of medical patients. Patients with
      nasogastric intubation had higher incidences of colonization with S. aureus, and
      gram-negative rods. All patients colonized with MRSA had received nasal tube
      feeding. Nasogastric intubation is considered to be a significant risk factor for
      MRSA colonization. The study in patients with nasogastric intubation demonstrated
      that patients with mechanical ventilation had a significantly higher incidence of
      colonization with gram-negative rods, such as P. aeruginosa, and a lower
      incidence of colonization with S. aureus. A incidence of MRSA colonization in
      patients with mechanical ventilation was significantly low. Mechanical
      ventilation is not necessarily considered to be a risk factor for MRSA
      colonization.

PMID- 8138676
TI  - [Roxithromycin treatment in patients with chronic lower respiratory tract disease
      -its clinical efficacy and effect on cytokine].
AB  - We demonstrated the efficacy of "long term" roxithromycin (RXM) treatment in 15
      patients with chronic lower respiratory tract disease (11 with diffuse
      panbronchiolitis and 4 with sinobronchial syndrome). (1) Fourteen (93.3%) of the
      15 patients showed improvement when assessed by the comprehensive improvement
      score, and they showed significant improvements in PaO2 (74.2 +/- 10.4 Torr to
      84.3 +/- 10.9 Torr, p < 0.01), %VC (86.9 +/- 20.2% to 96.0 +/- 21.9%, p < 0.001)
      and FEV1 (1.81 +/- 0.87 L to 2.14 +/- 1.08 L, p < 0.01) after RXM treatment. (2)
      Neutrophils accumulated in the pre-RXM treatment bronchoalveolar lavage (BAL)
      fluid and decreased in BAL fluid of patients responding to RXM treatment (49.8 +/
      28.3% to 17.1 +/- 15.7%, p < 0.01). Additionally, the levels of interleukin 1
      beta and interleukin 8 were significantly higher in BAL fluid of these patients
      than those in the healthy volunteers (p < 0.025, p < 0.01 respectively), and
      correlated with the neutrophil accumulation (r = 0.619, p < 0.05). These
      cytokines showed a decrease after RXM treatment. These results indicated that RXM
      acts by reducing pulmonary inflammation through reduction of neutrophil migration
      to inflammatory sites, and is effective on chronic lower respiratory tract
      disease.

PMID- 8138677
TI  - [Bacteremia of in-patients of the department of urology].
AB  - Thirty cases of bacteremia out of 1512 patients who had been admitted to our
      Department between February 1988 and June 1991 were reviewed. They consisted of
      22 males and 8 females and their age ranged from 32 to 88 years (mean 62.7). 25
      of the patients (83.3%) had malignant diseases of which bladder cancer (15 cases)
      was predominant and 5 had benign diseases. Gram positive bacteria were isolated
      in 18 cases (56.2%) and fungi in 4 cases (12.5%) from blood culture. Of these
      MRSA was most prevalent: 6 cases (18.8%), followed by S. epidermidis: 4 cases
      (12.5%), P. aeruginosa: 3 cases: E. faecalis: 3 cases and Corynebacterium: 3
      cases (9.4%). Analysing the onset of bacteremia for each case, in three cases
      urinary tract infections, in one case a surgical wound infection and in one case
      a skin infection were prominent before the diagnosis of bacteremia. From their
      background, 23 cases (76.7%) were so-called compromised hosts. A total of 7 cases
      had died, 6 cases of bladder cancer and one case of testicular cancer, five of
      them were on systemic anti-cancer chemotherapy. Of those cases who expired, P.
      aeruginosa was isolated in two cases, Candida in two cases, MRSA in one case and
      E. faecium in one case, Corynebacterium in one case. It was noteworthy that in
      two cases where blood cultures were positive for P. aeruginosa and one case where
      the blood culture proved positive for Candida, drastic decrease of the peripheral
      leukocyte number during anti-cancer chemotherapy was seen.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8138678
TI  - [Detection of Mycobacterium avium, M. intracellulare and M. kansasii in sputum by
      two-step PCR].
AB  - A DNA amplification assay using PCR, which consists of amplification of genus
      specific mycobacterial 16S rRNA gene as the 1st step and reamplification of the
      amplicon with species specific primers as the next step, could detect M. avium,
      M. intracellular and M. kansasii in the sputum. The results with type or standard
      strains showed that M. avium PCR and M. intracellular PCR were highly specific
      for identification of each species but M. kansasii PCR detected M. gastri besides
      M. kansasii. Among 22 clinical samples which were positive by PCR, the 17 results
      were confirmed by culture. The PCR detected 27 (7.5%) of nontuberculous
      mycobacteria from 360 sputum and showed that the 27 of NTM consists of 9 M.
      avium, 8 M. intracellulare, 5 M. kansasii, 1 reacted both M. avium and M.
      intracellulare and 4 unidentified.

PMID- 8138679
TI  - [Experimental study on the mechanisms of Chlamydia pneumoniae respiratory
      infection in mice with former chlamydial exposure].
AB  - To compare the differences in the severities, host defense responses and clinical
      courses C. pneumoniae respiratory tract infections between the initial and second
      challenge of chlamydia, an experimental C. pneumoniae respiratory infection model
      using mice was established and the following studies were carried out. For the
      initial infection mice were challenged with C. pneumoniae, strain TW-183, by
      nasal instillation. No animals died from this initial infection. The second
      exposure to C. pneumoniae, in the same manner, was done 35 days after the first
      challenge. Serial observation in the two groups of mice were done on the anti-C.
      pneumoniae IgG and IgM antibody titers of their sera, histopathological
      evaluations of their lungs and the formation of inclusion bodies in the lung
      sections. Focal inflammatory changes consisting of neutrophil and macrophage
      infiltration in the alveolar spaces of mice lungs three days after the initial
      challenge were observed, but there were no remarkable inflammatory changes in the
      lung sections of mice with the second challenge, with the exception of marked
      formation of bronchus-associated lymphoid tissues and perivascular accumulation
      of lymphoid cells. The numbers of inclusion bodies were very small in the lungs
      of mice with reinfection with chlamydia. These histopathological findings all
      disappeared within ten and five days after the initial and the second challenge,
      respectively. Anti-C. pneumoniae IgG antibodies showed a remarkable increase from
      seven days after the initial challenge and peak value was 1:512-1024 at 28-35
      days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138680
TI  - [Phase I study of edobacomab (E5) in patients with gram-negative sepsis].
AB  - A clinical Phase I study of E5, edobacomab, an anti-endotoxin monoclonal IgM
      antibody was carried out to evaluate its efficacy, safety and pharmacokinetics
      and in parallel, explore an optimum dosage in the treatment of patients with gram
      negative sepsis (incl. those suspected). A total of 10 patients were administered
      a dose of 1 mg/kg, 2 mg/kg or 4 mg/kg of E5 by infusion over one hour. 1. Peak
      blood levels after an intravenous dose of 1 mg/kg, 2 mg/kg and 4 mg/kg of E5 were
      9.9, 11.5 and 35.6 micrograms/ml, respectively and the half-lives of elimination
      were 8.7, 11.7 and 10.8 hours, respectively, about the same at all dose levels.
      The area under the blood concentration-time curve (AUC) were 129.8, 200.8 and
      574.4 micrograms.hr/ml, respectively, showing an increase in proportion with the
      dosage. 2. Urinary E5 concentration was not detectable in all the patients and
      renal excretion of unchanged E5 was not observed. 3. Out of the 8 patients with a
      positive pre-treatment endotoxin level with a value of above 9.8 pg/ml, those who
      showed its reduction to a level of below 9.8 pg/ml within one hour after dosing
      of E5 were 0 of 2 patients (0%) at a dose of 1 mg/kg, 3 of 3 (100%) at a dose of
      2 mg/kg and 1 of 3 (33.3%) at a dose of 4 mg/kg. 4. The clinical efficacy
      following a single intravenous dose of E5 was rated as being "good" or
      "excellent" for 3 of 3 patients (100%) at a dose of 1 mg/kg, 4 of 4 (100%) at a
      dose of 2 mg/kg and 2 of 3 (66.7%) at a dose of 4 mg/kg. 5. As for antipyretic
      effect as assessed by the mean value of temperature, a fall in fever to the level
      of 36 degrees C was noted from 12 hours after administration of E5 in the
      patients treated with 2 mg/kg. The degree of improvement in WBC, platelet count
      and CRP was also more evident in this 2 mg/kg group. 6. The safety was rated as
      "no problem in safety" for all 10 patients. No adverse reaction and clinical
      laboratory abnormalities suspected of their relation to E5 was observed. 7.
      Positive antibody (HAMA) response to E5 was observed in 2 of the 10 patients. In
      one patient (4 mg/kg) of them, response because negative 9 weeks later and in the
      other patient (1 mg/kg) it tended to decrease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8138681
TI  - [The first report of traveler's diarrhea associated with a newly described
      toxigenic Vibrio cholerae O139 strain in Japan].
AB  - A newly described Vibrio cholerae O139 was isolated from a patient who had
      traveled in India on April 1993. The patient experienced 5 to 6 watery diarrhea
      per day after he returned to Japan. The isolated strain registered as K111 did
      not agglutinate with O1-O138 antiserum and agglutinated with O139 antiserum. This
      strain resembled V. cholerae O1 strain in biochemical characters and had ctx and
      zot, although was resistant to the vibrio static agent O/129. This is the first
      report of cholera-like illness by the newly described toxigenic V. cholerae O139
      strain in Japan.

PMID- 8138682
TI  - [Phase II study of edobacomab (E5) in the treatment of gram-negative sepsis].
AB  - The efficacy, safety and usefulness of murine anti-endotoxin monoclonal IgM
      antibody "E5, an intravenous dose of 2 mg/kg" were evaluated in 88 patients with
      suspected Gram-negative sepsis from 37 institutes in Japan. Out of these, 74
      patients were evaluable for the efficacy, 85 for safety and 75 for clinical
      usefulness. In assessing the efficacy, the patients were divided into 3 groups
      based on the plasma endotoxin levels (Endospecy with new PCA treatment of
      plasma): H group with a level of above 9.8 pg/ml and M group with a level of 3.0
      9.8 pg/ml and L group with a level of below 3.0 pg/ml. 1. The efficacy rates as
      assessed following administration of E5 were 73.1% in the H group, 70.4% in the M
      group and 38.1% in the L group being higher in the groups with significantly high
      plasma endotoxin levels. 2. In both the H and M groups in whom plasma endotoxin
      levels were significantly high, the majority of the patients showed rapid
      reduction of the levels after administration of E5. 3. In all groups, improvement
      in body temperature, pulse rate, blood TNF-alpha and blood IL-6 was observed
      after treatment with E5. In the H and M groups with an endotoxin level of > or =
      3.0 pg/ml, improvement in platelet count as well as in CRP was noted. The H group
      showed also improvement in WBC. 4. Improvement in the shock score was noted in
      all the groups but was more outstanding in the H and M groups in the early stage
      of treatment. 5. Side effects were seen in 5 (5.9%) of 85 patients and all
      thought to be allergic in symptoms such as rash, itching, fever and flare. 6. The
      reaction to the prick test performed before administration of E5 was negative in
      all these 5 patients. For 3 of the 5 patients, anti-E5 IgE antibody was measured.
      In all of them, the IgE levels were higher than those of healthy controls. Also,
      in 47.6% of patients, an elevation of anti-E5 IgG antibody was noted two weeks
      after the administration. 7. Clinical laboratory abnormalities were observed in 3
      (3.5%) of 85 patients. They were an elevation of S-GOT.S-GPT and lowering of BUN,
      increased Al-p and decreased CH50, increased neutrophilia (%) and were all slight
      in the degree of the changes. 8. The clinical usefulness of E5 was evaluated for
      75 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8138683
TI  - [Experimental studies of pulsatile retrograde cerebral perfusion].
AB  - This study was investigated for the effects of pulsatile flow on retrograde
      cerebral perfusion under profound hypothermic circulatory arrest. Fifteen adult
      mongrel dogs were placed cardiopulmonary bypass and induced profound hypothermia
      of 20 degrees C at nasopharyngeal temperature. Five dogs were performed non
      pulsatile retrograde cerebral perfusion (NP-RCP) and 5 were pulsatile retrograde
      cerebral perfusion (P-RCP) for 60 minutes each group. The rest of 5 dogs were
      performed hypothermic circulatory arrest (HCA) without any circulatory assist.
      Retrograde cerebral perfusion flow rate was regulated to maintain an external
      jugular vein pressure of 20 mmHg by infusing oxygenated blood by way of bilateral
      maxillary vein. Regional cerebral blood flow (rCBF), cerebrospinal fluid pressure
      (CSFP), adenosine triphosphate (ATP) concentration of cerebral tissue, and water
      content of cerebral tissue were measured. The rCBF were no statistical difference
      between the two groups. CSFP and ATP concentration in both of NP-RCP and P-RCP
      were significantly higher than those of HCA. Water content of cerebral tissue in
      P-RCP were significantly lower than those of NP-RCP. We concluded that retrograde
      cerebral perfusion for 60 minutes protects the brain as the assistances of
      circulatory arrest and retrograde cerebral perfusion with pulsatile flow has the
      possibility to control brain edema as compared with non-pulsatile flow in dogs.

PMID- 8138684
TI  - [Change of mitral regurgitation before and after myocardial revascularization--is
      mitral repair required for ischemic mitral regurgitation?].
AB  - In twenty seven patients, intraoperative change of ischemic mitral regurgitation
      before and after coronary artery bypass grafting (CABG) was assessed using
      transesophageal echocardiography. The size of mitral regurgitation (MR) was
      determined by the area of MR color flow on the doppler echocardiogram. After
      CABG, MR area decreased in 20 patients (average: 3.7 cm2-->1.5 cm2), unchanged in
      one patient and increased in 6 patients (average: 17 cm2-->2.9 cm2). The change
      of MR area corresponded with the change of mitral annular diameter in 23 patients
      but uncorresponded in 2 patients. MR areas correlated exponentially with mitral
      annular diameters and the fair linear relation was observed between the
      postoperative to preoperative ratio of MR area and the postoperative increase in
      mitral annular diameter with the correlation of r = 0.81. When the larger MR area
      or mitral annular diameter before CABG was observed, the larger MR area after
      CABG remained, but annular diameter before CABG had more effect on postoperative
      MR area. No significant correlation was found between MR area and infarcted
      region, revascularized region, segmental wall motion etc. In conclusion, when the
      moderate or marked mitral annular dilatation was found in association with
      prominent ischemic mitral regurgitation, mitral annuloplasty with CABG should be
      considered.

PMID- 8138685
TI  - [Surgical treatment of incomplete endocardial cushion defect in elderly
      patients].
AB  - We experienced 5 surgical cases of incomplete endocardial cushion defect who were
      50 years old or older. Preoperatively, 3 cases were in New York Heart Association
      (NYHA) class II and 2 in class III. Catheterization study showed that systolic
      pulmonary arterial pressure was 24 to 48 (average; 38) mmHg and pulmonary-to
      systemic flow ratio was 3.4 to 8.1 (average; 5.2). Left ventriculography showed
      mitral valve regurgitation (grade I-1 cases, grade II-3, grade III-1) with cleft
      and goose neck sign in all cases. Single atrium and patent foramen ovalis were
      associated in each one case. At operation, suture of mitral cleft and patch
      closure of ostium primum defect from mitral valve side were performed.
      Postoperatively, NYHA class, cardiomegaly, pulmonary arterial pressure and mitral
      regurgitation improved remarkably in all patients. During the follow-up period
      from 18 to 126 months (average; 57), right bundle branch block and
      supraventricular arrhythmia in electrocardiogram disappeared in 3 of 4 and 4 of 5
      cases, respectively. Surgical treatment and postoperative course of incomplete
      ECD were reviewed in over-50-year-old patients, in reference to 17 surgical cases
      in Japan.

PMID- 8138686
TI  - [Advantages of combined antegrade/retrograde GIK cardioplegia for coronary artery
      bypass surgery].
AB  - We evaluated the advantages of combined antegrade and retrograde GIK cardioplegia
      in 65 patients undergoing CABG. Thirty seven patients were administered antegrade
      cardioplegia (Group A), whereas 28 patients were administered combined antegrade
      and retrograde cardioplegia (Group C). Enzyme release and hemodynamic data were
      obtained before the onset of CPB and at 1, 3, 6, 9, 12 and 24 hours after
      operation. Both groups were similar in age and incidence of diabetes, previous
      MI, PTCA, severity of coronary artery disease and emergent operation. In group A,
      antegrade cardioplegia produced poor anterior septal cooling in 17 patients
      (45%). To ensure adequate myocardial protection in these cases 9, patients were
      anastomosed saphenous vein graft first to LAD instead of IMA and perfused
      cardioplegic solution through the grafts. In group C, although adequate anterior
      septal cooling also could not be obtained with antegrade cardioplegia in 16
      patients (57%), after retrograde cardioplegia, anterior septal temperature fell
      below 10 degrees C. The use of IMA graft was more practiced in group C. (79% in
      group C versus 32% in group A, p < 0.05) Enzyme release (CPK-MB, %CPK-MB, LDH)
      and hemodynamic data (CI, LVSWI, RVSWI, RVEF, RVEDVI) were similar in both group.
      Furthermore, no significant difference were noted in the incidence of post
      operative LOS, PMI and ventricular arrhythmia. We concluded that the use of
      combined antegrade and retrograde cardioplegia is more effective than antegrade
      cardioplegia, because of adequate anterior septal cooling, and it will allow
      patients with severe and extent coronary artery disease to undergo safe IMA
      grafting.

PMID- 8138687
TI  - [The study on cerebral hemodynamics during selective cerebral perfusion].
AB  - This study was undertaken to clarify characterization on cerebral hemodynamics
      during deep hypothermic selective perfusion (SCP) in 18 pigs. Besides, the
      changes on cerebral hemodynamics were investigated with obstruction to venous
      drainage due to the clamp of superior vena cava (SVC) cannula. For SCP, blood was
      infused into aortic arch with the clamp of descending aorta, during 90 minutes at
      20 degrees C. We measured regional cerebral blood flow (CBF), intracranial
      pressure (ICP), and carotid arterial flow (CAF), and carotid arterial pressure.
      The carotid arterial pressure as perfusion pressure was not significantly
      correlated with CAF, CBF and ICP. Although CAF increased as pump flow rate
      increased, the relationship between pump flow and CBF was not significant.
      Moreover, SVC pressure showed a tendency to increase, as CAF increased. Both ICP
      and internal jugular vein pressure (IJVP) were significantly (p < 0.01) increase,
      and CAF was significantly (p < 0.05) decrease with the clamp of SVC cannula. On
      the other hand, both ICP and IJVP were significantly decrease, and both CAF and
      CBF were increase, without unclamp of SVC cannula. The results suggest that
      cerebral autoregulation is intact during deep hypothermic SCP, and hyperperfusion
      cause the increase of shunt flow in extracranial area, and besides, the increase
      of ICP with obstruction to venous drainage cause decrease in cerebral blood flow.

PMID- 8138688
TI  - [Predonation of autologous blood for up to 6 weeks in MAP solution prior to
      elective cardiac surgery].
AB  - Predonation of autologous blood was performed by means of MAP solution prior to
      elective cardiac surgery. MAP solution made it possible to store in the fashion
      of fluid for 6 weeks. In twenty-three patients, total 39 times, predonation of
      autologous blood was performed prior to the elective cardiac surgeries. The mean
      volume of predonated blood was 583 ml (400-1200 ml)/case with MAP solution and
      165 ml (0-400 ml)/case with conventional CPD solution, and the mean volume of
      total predonated blood was 748 ml (400-1600 ml)/case. The mean of the maximum
      duration of MAP predonate blood storage in individual cases was 25 days.
      Homologous blood transfusion was required in three cases. Two of the three cases
      had total aortic arch replacement under selective cerebral perfusion and the
      remainder was 76 year-old-man with unstable angina. In twenty cases (87%), any
      homologous blood transfusion was not performed throughout their clinical course.
      Twenty (95%) cases of 21 conventional cardiopulmonary bypass operation cases,
      except two selective cerebral perfusion cases, could successfully avoid
      homologous blood transfusion. To conclude, by using MAP solution, it became
      possible to take the longer period for predonation prior to elective surgery up
      to 6 weeks, compared with that in conventional way of storage by means of CPD
      solution. It seems worth-while to use MAP solution in order to take more
      predonated blood for avoiding homologous blood transfusion in elective cardiac
      surgery as far as possible.

PMID- 8138689
TI  - [Directions for reoperation of patients with Bjork-Shiley convexo-concave valve
      prosthesis, based on long-term experience].
AB  - Although a high incidence of strut fracture of the Bjork-Shiley convexo-concave
      (C-C) valve prosthesis has been reported, it is still controversial whether the
      prosthesis functioning normally should be replaced electively. To clarify our
      policy for this issue, we reviewed 28 patients who had undergone mitral valve
      replacement with a C-C valve prosthesis, and evaluated long-term results
      according to STS guidelines. The incidence of valve-related complications
      expressed as % patient-year were; structural deterioration 0.30, nonstructural
      dysfunction 0.30, thromboembolism 1.20. There were no thrombosed valves,
      anticoagulant-related hemorrhage or prosthetic valve endocarditis. The actuarial
      free rate after valve replacement with the C-C at 10 years, constructed by the
      Kaplan-Meier method, were compared with those with St. Jude Medical (SJM) valve
      prosthesis. (1) Actuarial survival: 77.9 vs 87.3 (NS), (2) Reoperation-free: 91.6
      vs 98.0 (p < 0.05), (3) thromboembolism-free: 83.7 vs 83.9 (NS), (4) Event-free
      (hospital death+reoperation+valve-related complications: 71.2 vs 77.7 (NS). The
      long-term results with the C-C were compatible to those with a SJM valve
      prosthesis. However, if a strut fracture occurs, it is very difficult to save the
      patient's life. The hospital mortality of re-replacement of valve prosthesis
      during the last 10 years, at our institute, was 2.6%, which is almost equal to
      the cumulative risk of strut fracture of the C-C valve after 10 years
      (3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138690
TI  - [Comparison of long-term clinical results and cost-effectiveness of percutaneous
      coronary angioplasty and coronary artery bypass grafting].
AB  - Cost-effectiveness was studied in 313 cases who had PTCA and 161 cases who had
      CABG as a first measure of interventional therapy for their coronary heart
      disease. Follow-up time ranged from 2 years to 5 years and 9 months with a mean
      interval of 3 years and 10 months. In the PTCA group a mean of 1.33 successfully
      dilated vessels/patient was obtained, but a total of 100 additional PTCA or
      bypass surgery procedure was necessary in the follow-up period. In the CABG group
      a mean of 2.60 patent grafts/patient was obtained. Mean length of hospital stay
      and charge was 21.9 days and 2,071 thousand yen in the PTCA group, and 82.2 days
      and 5,122 thousand yen in the CABG group through the entire follow up period.
      Cardiac event-free survival rate was significantly worse in the PTCA group. In
      the subgroup of two vessel disease, mean number of successfully dilated targets
      or patent grafts was 1.32 in the PTCA group and 1.88 in the CABG group. Total
      length of hospital stay and charge was 24.1 days and 2,352 thousand yen in the
      PTCA group and 86.2 days and 4,903 thousand yen in the CABG group. Cardiac event
      free survival rate was significantly worse in the PTCA group. In the subgroup of
      three vessel disease, PTCA yielded 1.34 dilated target vessels, whereas CABG 2.66
      patent grafts, which was two times more than the former one. Total length of
      hospital stay and charge was 32.7 days and 2,612 thousand yen in the PTCA group,
      and 82.4 days and 5,225 thousand yen in the CABG group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138691
TI  - [Evaluation of the exercise capacity recovery process after lung cancer surgery
      by exercise test and expire gas analysis].
AB  - This study was conducted to evaluate the numerical changes and the recovery
      process in exercise capacity over time, and to establish new criteria that will
      objectively evaluate the recovery in exercise capacity after lung surgery using
      an expired gas analysis incorporating an exercise test. The subjects consisted of
      47 patients that underwent curative resection (only lobectomy) for lung cancer in
      the four years from 1989 to 1992 that were able to undergo expired gas analysis
      incorporating an exercise test before and after surgery. The expired gas analysis
      were performed within one week prior to surgery and over a period from 14 to 449
      days after surgery, maximum oxygen consumption (VO2max) and anaerobic threshold
      (AT) measured, and the VO2max/m2 and AT/m2 were calculated as an index by
      dividing by the body surface area (m2). In addition, in order to examine the
      changes in exercise capacity after surgery, the presurgical values were used as
      100, and the rate of change after surgery found. These rate were divided into the
      following measuring times, and the postsurgical changes over time analyzed. The
      postsurgical measuring times were divided into five groups from 14-30 days (n =
      11), from 31-90 days (n = 25), from 91-180 days (n = 8), from 181-270 days (n =
      19), and greater than 271 days (n = 8) after surgery.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138692
TI  - [Subaortic stenosis in coarctation or interruption of the aorta--changes of left
      ventricular outflow tract dimension after aortic arch repair and pulmonary artery
      banding].
AB  - Left ventricular outflow tract (LVOT) dimension was measured in seven patients
      with coarctation (CoA) or interruption (IAA) of the aorta before and after aortic
      arch repair and pulmonary artery banding. The age of patients ranged 3 to 69
      (mean 16) days, the weight 3.0 to 3.9 (mean 3.4) kg. Associated cardiac anomalies
      were VSD in 6, MA and DORV in 1. In five patients compared by ultrasound,
      preoperative LVOT dimension ranged from 3.5 to 5.0 (mean 4.4) mm with the ratio
      to the normal aortic valve dimension (n-AVD; 16.6 x BSA0.6) from 54 to 82 (mean
      69)%. Postoperative dimension increased 5.0 to 7.4 (mean 5.7) mm and the ratio to
      the n-AVD increased 65 to 89 (mean 80)%. In three patients compared by LV graphy,
      preoperative LVOT dimension ranged from 4.0 to 4.5 (4.2) mm and the ratio ranged
      from 61 to 72 (68)%. Postoperative dimension increased from 4.5 to 6.7 (5.3) mm,
      and 74 to 80 (78)% to n-AVD after operation. Postoperative pressure gradients
      between LV and ascending aorta in each patient were 1 to 9 (mean 6) mmHg. In any
      patients, LVOT obstruction did not advance after aortic arch repair and pulmonary
      artery banding.

PMID- 8138693
TI  - [A case report of thymolipoma with high titer of serum anti-acetylcholine
      receptor antibodies--thymolipoma, a review of 49 reports in Japan].
AB  - A 22-year-old man was diagnosed as thymolipoma by chest CT scan & MRI. In spite
      of high titer of serum anti-acetylcholine receptor antibodies, he showed no
      symptom of myasthenia gravis. An extended thymectomy was done successfully. Tumor
      was 21 x 15 cm in size and 620 g in weight. Histopathologically the tumor was
      diagnosed as thymolipoma. The titer of serum anti-acetylcholine receptor
      antibodies was decreased within normal limit and postoperative course was
      uneventful. To our knowledge, the 49 case reports in Japan were reviewed.

PMID- 8138694
TI  - [A concomitant operation of Damus-Kaye-Stansel procedure, atrioventricular
      valvuloplasty and total cavopulmonary connection].
AB  - A 2-year-old girl with single ventricle and coarctation of aorta, who received
      subclavian flap aortoplasty and pulmonary artery banding at 30 days of age,
      developed subaortic stenosis and atrioventricular valve regurgitation. At the age
      of 2 years and 10 months, physiologic correction with atrioventricular
      valvuloplasty, Damus-Kaye-Stansel procedure, and total cavopulmonary connection
      were performed concomitantly. She showed uneventful convalescence, and
      postoperative cardiac catheterization revealed trivial atrioventricular valve
      regurgitation with a mild pressure gradient between the left ventricle and aorta.

PMID- 8138695
TI  - [Total aortic replacement in a patient with extensive thoracoabdominal aortic
      aneurysm--a case report].
AB  - A 35-year-old woman with a form fruste of Marfan's syndrome, presented the
      extensive thoracoabdominal aortic aneurysm. CT scan, MRI and aortogram revealed
      that she had a true aneurysm of ascending aorta and aortic arch and chronic
      DeBakey IIIb dissecting aneurysm extending throughout the descending thoracic and
      abdominal aorta. The surgical treatment was consisting of two staged operations.
      At the first operation, ascending aorta and aortic arch were reconstructed under
      cardiopulmonary bypass and selective cerebral perfusion. Elephant trunk method
      was employed for the second operation. The second operation was performed by
      graft replacement of the entire descending thoracic and abdominal aorta with
      reattachment of intercostal and visceral arteries. She discharged the hospital
      without any complication including paraplegia.

PMID- 8138696
TI  - [A case of multicentric Castleman lymphoma in the left pulmonary hilum and
      mediastinum].
AB  - A 29-year-old female who complained of low grade fever was detected an abnormal
      shadow in the left pulmonary hilum on a chest roentgenogram. Thoracotomy revealed
      that the tumorous lesion originated from left hilar lymph node. Left hilar and
      mediastinal lymph nodes were extirpated. Histopathologically, three of all the
      resected lymph nodes were diagnosed as Castleman lymphoma (plasma cell type).
      Therefore, not only the main lymph node but also the associating lymph nodes
      should be completely extirpated, since, in this disease, especially plasma cell
      type, the lesions are often multicentric.

PMID- 8138697
TI  - [A case of left ventricular outflow tract obstruction after repair of ostium
      primum defect].
AB  - We report a 3-year-old girl with left ventricular outflow tract obstruction after
      repair of ostium primum defect. The girl had closure of an ostium primum defect
      performed at the age of 1 year. Two years later, she developed left ventricular
      hypertrophy with systolic ejection murmur. Echocardiography showed discrete
      stenosis of the left ventricular outflow tract. Cardiac catheterization showed a
      peak systolic gradient of 63 mmHg across the left ventricular outflow tract. At
      the reoperation, the fibrous tissue was excised and myectomy was done. After the
      operation the peak systolic gradient across the left ventricular outflow tract
      disappeared. Since there is a possibility of occurrence of the left ventricular
      outflow tract obstruction after repair of atrioventricular septal defect, long
      term follow up is mandatory.

PMID- 8138698
TI  - [Case report of intraatrial RL-shunt after the repair of ventricular septal
      perforation].
AB  - A 78-year-old woman with ventricular septal perforation (VSP) after acute
      myocardial infarction was described in this report. Arterial oxygen tension
      (PaO2) extremely decreased after the repair of VSP. There was the marked
      difference in blood oxygen tension between left atrial blood and radial arterial
      blood, and trans-esophageal color echogram showed the intra-atrial RL shunt.
      Autopsy showed a small atrial septal defect (ASD) at foramen ovale. Right atrial
      pressure was higher than left atrial pressure after the repair of VSP because of
      right heart failure. These made the postoperative management complicated.

PMID- 8138699
TI  - [Pre and postoperative management of a patient after cardiac transplantation
      performed in UCLA].
AB  - The patient with dilated cardiomyopathy (NYHA grade 4) underwent cardiac
      transplantation at University of California, Los Angeles. Postoperative
      management in our institute consisted 1) cardiac biopsy, 2) measurement of blood
      concentration of cyclosporin, 3) serum anti-CMV titer, 3) echo cardiography, 4)
      counts of lymphocyte subsets. Cardiac rejection (Ib) was observed 2 months after
      transplantation and steroid pulse therapy (methylprednisone 500 mg/day) was
      performed for 3 days. Blood concentration of cyclosporin was decreased with
      administration of probucol and increased with diltiazem. Presently, the patient
      is stable and back to normal work.

PMID- 8138700
TI  - [A case of simultaneous operation of recurrent aortic arch aneurysm and lung
      cancer].
AB  - A simultaneous operation was successfully performed on a 70-year-old man with
      recurrent aortic arch aneurysm and squamous cell carcinoma of the lung. Via a
      left thoracotomy, left lower lobectomy with lymph node resection was performed,
      and via the same incision, aneurysmectomy with graft replacement was performed
      under the hypothermic cerebral circulatory arrest. The patient was readmitted
      because of brain metastasis 10 months later, and died 11 months postoperatively.
      The present report suggests that selected cases of thoracic aortic aneurysm with
      malignant tumor are safely able to undergo simultaneous operations. This is the
      first report in Japan of aortic arch aneurysmectomy and lobectomy performed
      during the course of one operation.

PMID- 8138701
TI  - [Anomalous origin of the left coronary artery from the pulmonary artery with
      rheumatic mitral stenosis--a successful surgical case].
AB  - A 43-year-old woman in whom anomalous origin of the left coronary artery from the
      pulmonary artery, associated with rheumatic mitral stenosis, was surgically
      corrected. She underwent aortic implantation of anomalous left coronary artery
      and mitral valve replacement. It was feasible to obtain a sufficient length of
      the left main trunk excising a large cuff of pulmonary artery wall surrounding
      the ostium of anomalous left coronary artery, without transecting pulmonary
      artery. This surgical case is first reported about BWG syndrome associated with
      rheumatic valvular disease.

PMID- 8138702
TI  - [Esophageal duplication with esophago-bronchial fistula].
AB  - In a case of 51-year-old woman with an esophago-bronchial fistula located in the
      right B2 bronchus, we found a tubular type of esophageal duplication
      communicating with the esophagobronchial fistula by examinations of
      esophagography and endoscopy. It was diagnosed as tubular type I double barreled
      type of esophageal duplication by Akaboshi's Classification. She successfully
      underwent resection of the accessory esophagus combined with the fistula and the
      adjacent pulmonary tissues. Squamous epithelium and smooth muscle tissue were
      observed in the resected esophageal specimen. Double barreled type of esophageal
      duplication is one of the rare malformation, and we have found 12 reported cases
      including our one case in the Japanese literatures. Moreover our case is the
      first one whose accessory esophagus were combined with an esophagobronchial
      fistula.

PMID- 8138703
TI  - [Valve replacement for congenital mitral stenosis--a case report and a review of
      Japanese literature].
AB  - A 3-year-old girl with congenital mitral stenosis associated with severe
      pulmonary hypertension was successfully operated upon. The mitral stenosis was a
      commissural fusion type with severe infravalvular changes. First attempt to fix
      regurgitation with mitral commissurotomy was unsuccessful, which was followed by
      prosthetic valve replacement. Her postoperative course was uneventful. A review
      of Japanese literatures is reviewed as well.

PMID- 8138704
TI  - [Aortic valve replacement in a patient with chronic idiopathic thrombocytopenic
      purpura].
AB  - We reported a case of aortic valve replacement in a patient with chronic
      idiopathic thrombocytopenic purpura (ITP). We used high-dose intravenous
      gammaglobulin therapy (400 mg/kg/day) for five days to increase the platelet
      prior to the operation. The number of platelet was 8-10 x 10(4)/microliters at
      admission and it was increased to 23 x 10(4)/microliters before surgery. Aortic
      valve was replaced to SJM#21A prosthesis using cardiopulmonary bypass. The
      platelet was transfused after the bypass. Perioperative hemorrhage was moderate
      and postoperative course was uneventful. We believe that high-dose intravenous
      gammaglobulin therapy for ITP is effective to minimize perioperative hemorrhage
      for open heart surgery.

PMID- 8138705
TI  - [A case of ruptured left ventricular aneurysm due to syphilitic myocarditis].
AB  - This case involved a 20-year-old male who on May, 14, 1992, lost consciousness
      while working and went into a state of shock. He was taken to a hospital, where
      cardiac tamponade was diagnosed. He was later transferred to this hospital. Based
      on the results of echocardiography, coronary arteriography and left
      ventriculography, a ruptured ventricular aneurysm was diagnosed. The patient
      underwent emergency surgery. Serologic tests for syphilis performed at admission
      were definitely positive. Histopathological examination of the wall of the
      ventricular aneurysm disclosed fibrous myocarditis and peripheral coronary
      endarteritis accompanied by infiltration of plasma cells and lymphocytes.
      Immunohistological study revealed treponeme in the histiocytes of the aneurysmal
      wall. The diagnosis was a ruptured ventricular aneurysm caused by syphilitic
      myocarditis. Since the advent of penicillin therapy, cardiovascular syphilis,
      particularly syphilitic myocarditis, has become a rare disease. The chief
      interest of this case is that treponeme was detected in the lesion of
      myocarditis.

PMID- 8138706
TI  - [Complications of femoral artery cannulation in aortic arch related operations].
AB  - Two cases of complications of femoral artery cannulation in aortic arch related
      operations were reported. In the first case of them, we encountered massive
      cerebral infarction after concurrent CABG and aortic arch aneurysm operation. The
      patient also had untreated abdominal aortic aneurysm with mural thrombus. It was
      strongly suspected that retrograde perfusion from femoral artery cannulation made
      the mural thrombus free and the cerebral embolism subsequently occurred. The
      second case was acute aortic dissection with massive aortic valve regurgitation.
      Ascending and arch aorta replacement with resuspension of aortic valve was
      performed under selective cerebral perfusion. After the operation,
      myonephropathic metabolic syndrome appeared maybe for occlusion of femoral artery
      during cardiopulmonary bypass. The patient needed to receive hemodialysis therapy
      for three weeks after the operation. Through these two cases of complications of
      femoral artery cannulation, the potential of trouble in retrograde perfusion from
      femoral artery was noted. After these experiences, we planed to avoid retrograde
      perfusion from femoral artery as far as possible, especially in cases with mural
      thrombus or possibly detachable atheroma in ether descending or abdominal aorta.
      In cases, in which femoral artery cannulation can not be avoided, the duration of
      femoral artery occlusion should be made as short as possible. In order to shorten
      the duration, we usually make one supplemental branch in aortic prosthetic graft.
      After completion of aortic reconstruction, the perfusion in the rewarming period
      is made through the supplemental branch and the femoral artery can be perfused
      earlier. This supplemental branch is useful in preventing myonephropathic
      metabolic syndrome after surgery, especially in cases of prolonged
      cardiopulmonary bypass time.

PMID- 8138707
TI  - [Left atrial isolation for chronic atrial fibrillation caused by mitral valvular
      stenosis and regurgitation].
AB  - Surgical isolation of the left atrium was performed for the treatment of chronic
      atrial fibrillation secondary to mitral valvular disease in a 65-year-old woman
      who underwent mitral valvular replacement. Left atrial isolation was simple
      procedure, prolonging the usual paraseptal atriotomy toward the both mitral
      valvular commissures anteriorly and posteriorly. The incision was conducted two
      centimeters apart from the mitral valve annulus, and cryoablation was added at
      the edges to ensure isolation of the residual left atrium. We suggest performing
      this simple procedure in patients with chronic atrial fibrillation undergoing
      mitral valvular replacement, in whom correction of irregular beat and compromised
      hemodynamics can be obtained.

PMID- 8138708
TI  - [Reoperation for late pseudoaneurysm in the ascending aorta following the
      modified Bentall procedure--a case report].
AB  - We performed reoperation for annuloaortic ectasia (AAE) in a patient with
      Marfan's syndrome. The initial operation was the modified Bentall procedure, in
      which the root of the ascending aorta and the aortic valve were replaced with a
      composite graft with a prosthetic mechanical valve, and the coronary arteries
      were reconstructed by direct anastomosis to the right coronary ostium or with an
      interposing graft to the left coronary ostium. At 1 year and 6 months after the
      initial operation, a pseudoaneurysm developed in the ascending aorta following
      the reconstructed coronary ostium on the right side was detached. At reoperation,
      the hole in the composite graft was closed, but the right coronary artery could
      not be reconstructed. Her postoperative course was uneventful. In addition,
      Piehler's method is effective for reconstruction of the coronary arteries,
      especially for patients with AAE in the Marfan's syndrome.

PMID- 8138709
TI  - Lipoprotein fractionation in deuterium oxide gradients: a procedure for
      evaluation of antioxidant binding and susceptibility to oxidation.
AB  - Oxidative modifications of lipoproteins appear to contribute to their
      atherogenicity. Very low and low density lipoproteins (VLDL and LDL) are
      protected against these modifications by antioxidants that can be incorporated in
      vivo or in vitro into the particles. We describe here ultracentrifugal procedures
      for isolation of VLDL and LDL that do not require subsequent dialysis or buffer
      equilibration. Lipoproteins were isolated in buffers with physiological ionic
      composition prepared in D2O (deuterium oxide). This allowed measurements of the
      content of antioxidants and of the susceptibility to oxidation of the isolated
      LDL without further manipulations. Conventional ultracentrifugal methods use high
      salt concentrations and require additional steps to eliminate them. This
      introduces uncertainties in the evaluation of antioxidant binding and on
      measurements of their effect on VLDL and LDL oxidation. With the method
      described, the composition of the isolated VLDL and LDL was indistinguishable
      from that of fractions isolated with KBr gradients. Also, the content of alpha
      tocopherol was similar. LDL isolated with KBr solutions appeared to bind 20-45%
      more of the probucol present in serum than LDL isolated in isotonic solutions
      prepared with D2O. This was the case with probucol incorporated into plasma or
      serum in vivo or in vitro. Five out of seven LDL isolated with the D2O procedure
      from different human sera appeared more resistant to Cu(2+)-catalyzed oxidation
      than those obtained with KBr gradients from the same serum. In addition to the
      gradient procedure, we also describe a preparative version of the method that can
      be used with multiple samples.

PMID- 8138710
TI  - Serum gangliosides in mice with metastatic and non-metastatic brain tumors.
AB  - The content of serum gangliosides was examined in VM and C57BL/6J (B6) mice that
      contained subcutaneous metastatic (VM) and non-metastatic (CT-2A) brain tumors,
      respectively. Gas-liquid chromatography (GLC) and high performance thin-layer
      chromatography (HPTLC) were used to analyze the serum gangliosides. N
      glycolylneuraminic acid (NeuGc) accounted for greater than 90% of the total serum
      sialic acid content in each mouse strain (5.53 nmol and 2.05 nmol per ml serum,
      respectively). GM2-NeuGc was the major serum ganglioside detectable in both the
      normal and tumor-bearing mice of each strain. Shedding of tumor gangliosides into
      the serum occurs in various murine non-neural tumors and in human gliomas and
      neuroblastomas, but has not been previously studied in murine brain tumors. Our
      results show that serum ganglioside concentration was reduced in VM mice bearing
      the metastatic VM tumor, but was increased in B6 mice bearing the non-metastatic
      CT-2A tumor. These changes in concentration, however, were not associated with
      marked changes in serum ganglioside distribution. As serum gangliosides are
      synthesized in the liver, the differences in serum ganglioside concentration in
      the tumor-bearing mice may arise more from changes in liver function than from
      differences in tumor shedding.

PMID- 8138711
TI  - Developmental sensitivity of the brain to dietary n-3 fatty acids.
AB  - The developing brain readily incorporates dietary fatty acids, while the adult
      brain is refractory to changes in fatty acid composition. In order to localize
      the time in development when this transition occurs, chicks were fed large
      amounts of n-3 fatty acids from fish oil beginning at 0, 1, 2, or 3 weeks of age.
      Control chicks were fed a soybean oil-based diet, as were the experimental chicks
      before introduction of the fish oil diet. Resistance to diet-induced increases in
      brain n-3 fatty acid levels began at 2 weeks of age, and was substantial at 3
      weeks. Docosahexaenoic acid was particularly resistant to change as the brain
      matured, increasing by 38% when fish oil was fed from time of hatching, but only
      by 8% when fish oil feeding was delayed until 3 weeks of age. Dietary fish oil
      caused a compensatory decrease in brain n-6 fatty acids, and this decrease
      occurred even at later time points when the rise in brain n-3 fatty acids was
      much less prominent. The liver incorporated high levels of n-3 fatty acids at all
      ages, and compensated by decreasing monounsaturated fatty acids at early time
      points and n-6 fatty acids at later time points. These results show that
      resistance to changes in brain fatty acid composition is evident at a relatively
      early age, before brain development is complete.

PMID- 8138712
TI  - Sources of cholesterol for kidney and nerve during development.
AB  - Rats were injected intraperitoneally with [3H]water; 2 h later, they were killed,
      dissected, and cholesterol was isolated from several tissues. Measurement of
      incorporated radioactivity allowed for calculation of the absolute amount of
      newly synthesized cholesterol appearing in a tissue. We determined the daily rate
      of synthesis of cholesterol in the sciatic nerve and kidney of rats at 10 time
      points between birth and 35 days of age. We compared this to the daily rate of
      accumulation of total cholesterol. For the sciatic nerve, total accumulation of
      cholesterol during development was always matched by accumulation of newly
      synthesized cholesterol, indicating that sciatic nerve synthesizes all of its own
      cholesterol. This was so independently of whether, at weaning, animals were
      placed on a cholesterol-free diet or a 2% cholesterol-containing diet. In
      contrast, in kidney, during the suckling period, only 25% of the accumulated
      cholesterol was newly synthesized; the remainder came from the circulation. Upon
      weaning to a 2% cholesterol-containing diet, there was increased local synthesis
      of cholesterol in kidney, so that within a few days about 50% was locally
      synthesized. If, however, the animals were weaned onto a cholesterol-free diet,
      there appeared to be further up-regulation of cholesterol biosynthesis in kidney;
      now all of the cholesterol accumulating was accounted for by that newly
      synthesized. Thus, the nerve is invariant with respect to self sufficiency for
      cholesterol; the kidney changes in this regard during development and as a
      function of diet.

PMID- 8138713
TI  - Regulation by nutritional status of lipids and apolipoproteins A-I, A-II, and A
      IV in inbred mice.
AB  - This study illustrates that genetic strain and feeding status can markedly
      influence tissue lipid concentrations and mRNA levels of apolipoprotein genes.
      C57BL/6 and BALB/c mice were maintained for 2 weeks on four test diets differing
      in amount of cholesterol and type of fat, and fasted for 4 h or 16 h prior to
      collection of tissues. For both strains, the primary effect of fasting from 4 h
      to 16 h was to paradoxically elevate triglyceride levels in plasma and liver, and
      to elevate hepatic apoA-IV mRNA levels. Triglyceride secretion rates, estimated
      after the injection of Triton WR-1339, suggested that elevations in plasma
      triglyceride levels were due to reduced clearance of very low density
      lipoproteins. Although plasma glucose levels decreased with fasting time for both
      strains, insulin levels decreased for BALB/c but not C57BL/6 mice regardless of
      diet. This suggests that factors thought to be mediated by insulin, (e.g., plasma
      free fatty acid concentrations; hepatic apoA-IV mRNA levels) may be influenced by
      local changes in insulin sensitivity, which are controlled genetically and are
      not reflected by plasma insulin levels. In summary, nutritional status influences
      a constellation of factors involved in lipid transport that also show strong
      genetic components and may influence subsequent analyses of gene expression in
      the mouse system.

PMID- 8138714
TI  - Effect of apolipoprotein C-I peptides on the apolipoprotein E content and
      receptor-binding properties of beta-migrating very low density lipoproteins.
AB  - To evaluate the role of apolipoprotein (apo) C-I in inhibiting lipoprotein
      binding to the low density lipoprotein receptor-related protein (LRP), a putative
      lipoprotein remnant receptor, apoC-peptide fragments were prepared by chemical
      synthesis or by cyanogen bromide cleavage of intact apoC-I. In ligand-blotting
      assays, peptides corresponding to residues 1-38, 10-57, 20-57, 30-57, and 40-57
      proved ineffective, but intact apoC-I was very effective, at inhibiting the
      binding of apoE-enriched beta-migrating very low density lipoproteins (beta-VLDL)
      to the LRP. Studies of the displacement of 125I-labeled apoE from apoE-enriched
      beta-VLDL showed that the largest peptide (residues 10-57) was two-thirds as
      effective as intact apoC-I; the other peptides were highly ineffective (residues
      40-57, 1-38) or only partly effective (residues 20-57, 30-57). Changes in the
      intrinsic tryptophan fluorescence and helix content indicated that the largest
      peptide was similar to apoC-I in lipid binding affinity, while the other peptide
      fragments showed little or no affinity for either unilamellar or multilamellar
      vesicles of dimyristoyl-phosphatidylcholine. These findings suggest that the
      ability of apoC-I fragments to displace apoE from beta-VLDL is largely, but
      perhaps not exclusively, a reflection of their ability to bind to membranous
      bilayers and that apoC-I blocking of the interaction between apoE-rich beta-VLDL
      and the LRP probably involves displacement of a critical amount of the apoE from
      the surface of this lipoprotein.

PMID- 8138715
TI  - Simultaneous measurements of chylomicron lipolysis and remnant removal using a
      doubly labeled artificial lipid emulsion: studies in normolipidemic and
      hyperlipidemic subjects.
AB  - An artificial chylomicron-like lipid emulsion doubly labeled with
      tri[(N)3H]oleoylglycerol ([3H]TO) and cholesteryl [1-14C]oleate ([14C]CO) was
      infused intravenously into human subjects with the purpose of simultaneously
      measuring the plasma disappearance rates (residence time, RT) of [14C]CO, which
      represents solely the splanchnic organ uptake of the remnant chylomicron core,
      and of [3H]TO, which combines the remnant disappearance with the shedding off of
      chylomicron triglycerides by the action of lipoprotein lipase. Thus, the fraction
      of the particle triglyceride content that is removed before the remnant is taken
      up is expressed as a delipidation index (DI = 1 - RT of [3H]TO/RT of [14C]CO. The
      present procedure has an advantage over the use of chylomicrons labeled with
      retinyl ester or radioactive triglycerides alone that represent, respectively,
      the chylomicron remnant or the whole particle metabolism only. When normal
      subjects as well as primary hyperlipidemic subjects were studied, the plasma
      triglyceride concentration was directly related to [14C]CO RT and [3H]TO RT, but
      inversely related to the delipidation index. There may be different patterns of
      relations between these parameters of chylomicron metabolism in primary and in
      secondary hyperlipidemias, as well as under the action of drugs that influence
      the metabolism of lipoproteins.

PMID- 8138716
TI  - Abnormal metabolism of postprandial lipoproteins in patients with non-insulin
      dependent diabetes mellitus is not related to coronary artery disease.
AB  - To investigate whether abnormalities in alimentary lipemia explain the increased
      risk of coronary artery disease (CAD) in subjects with non-insulin-dependent
      diabetes mellitus (NIDDM), we performed an oral vitamin A fat-load test in four
      groups of men (each n = 15): 1) NIDDM and angiographically verified CAD
      (DM+CAD+): 2) CAD but no diabetes (DM-CAD+); 3) NIDDM but no CAD, excluded by an
      exercise thallium scan (DM+CAD-); and 4) healthy control subjects (DM-CAD-). The
      groups were matched for age and body mass index. Plasma obtained after an
      overnight fast and 2, 3, 4, 6, 9, 12, and 24 h after a fatty meal (78 g fat,
      345,000 IU retinyl palmitate [RP]) was separated by density gradient
      ultracentrifugation into six fractions of triglyceride (TG)-rich lipoproteins:
      Svedberg flotation units (Sf) > 3200, Sf 1100-3200, Sf 400-1100, Sf 60-400, Sf 20
      60, and Sf 12-20. TG, RP, and cholesterol concentrations were measured in plasma
      and in each lipoprotein fraction. Postprandial plasma TG responses were
      significantly larger in both NIDDM groups than in the healthy control group. The
      most marked differences were observed in the Sf 60-400 lipoproteins, whether
      measured as TG or RP responses. However, there were no differences between the
      DM+CAD+ and DM+CAD- groups. The between-group differences in alimentary lipemia
      were only partially explained by fasting TG levels. In contrast to the healthy
      subjects, no significant negative correlation was observed in the NIDDM patients
      between alimentary lipemia and lipoprotein lipase activity, implying an
      abnormality of the lipolysis of TG-rich particles in NIDDM. Levels of atherogenic
      postprandial remnant lipoproteins are increased in NIDDM. However, in this study
      the magnitude of alimentary lipemia did not distinguish NIDDM patients with CAD
      from those without CAD symptoms and normal exercise thallium scans.

PMID- 8138717
TI  - Rapid determination of apolipoprotein E phenotypes from whole plasma by automated
      isoelectric focusing using PhastSystem and immunofixation.
AB  - The influence of the genetic apolipoprotein (apo) E isoforms on human plasma
      lipoproteins is well established. There is, however, still a need for a
      phenotyping procedure applicable in laboratories not specialized in lipid
      research. To this end, we developed a rapid, automated electrophoresis method for
      apoE phenotyping. Either self-made or commercially available precasted gels can
      be used. Fresh or frozen samples corresponding to 0.1 microliter of plasma are
      applied automatically after lipid extraction in a urea-containing buffer onto the
      gel and isoelectric focusing is carried out for 45 min. Thereafter, apoE bands
      are precipitated by specific polyclonal antibodies and visualized by automated
      silver staining. The method is reliable, easily and quickly performed, and not
      restricted to specialized laboratories.

PMID- 8138718
TI  - Quantification of cholesterol in all lipoprotein classes by the VAP-II method.
AB  - We have developed a high resolution microvolume Vertical Auto Profile (VAP)
      method for the simultaneous measurement of cholesterol in all lipoprotein
      classes, including lipoprotein[a] (Lp[a]) and intermediate density lipoprotein
      (IDL). This method, designated as VAP-II, uses a non-segmented continuous flow
      (controlled-dispersion flow) analyzer for the enzymatic analysis of cholesterol
      in lipoprotein classes separated by a short spin (47 min) single vertical
      ultracentrifugation. Cholesterol concentrations of high (HDL), low (LDL), very
      low (VLDL), and intermediate (IDL) density lipoproteins, as well as Lp[a], are
      determined by decomposing the spectrophotometric absorbance curve, obtained from
      the continuous analysis of the centrifuged sample, into its components using
      software developed in this laboratory. Analysis by VAP-II is rapid and sensitive
      (as little as 40 microliters plasma is required per assay). The resolution of
      lipoprotein peaks is considerably enhanced in the present analyzer compared to
      the previous analyzer (VAP-I, which used the Technicon AutoAnalyzer); improvement
      is especially noticeable for Lp[a] and IDL. Total and lipoprotein cholesterol
      values obtained by VAP-II correlated well with the values obtained by Northwest
      Lipid Research Laboratories (NWLRL). VAP-II Lp[a] cholesterol values also
      correlated well with the Lp[a] mass values obtained by an immunoassay technique
      performed at NWLRL (r = 0.907). The reproducibility and accuracy of the method
      are within the requirements of the CDC-NHLBI (Centers for Disease Control
      National Heart, Lung, and Blood Institute) Lipid Standardization Program.

PMID- 8138719
TI  - Dietary regulation of cholesterol esterase mRNA level in rat pancreas.
AB  - This study investigates the effect of a high fat/high cholesterol diet on
      cholesterol esterase biosynthesis in rat pancreas. Results showed that rats fed a
      high fat/high cholesterol diet, with or without bile salt supplementation,
      exhibited increased levels of pancreatic cholesterol esterase mRNA. An average of
      a 2-fold increase in cholesterol esterase mRNA was observed after 1 day of
      feeding the atherogenic diet. A maximal 3- to 4-fold induction was observed after
      4 days on the special diet. The level of pancreatic cholesterol esterase mRNA
      declined subsequently, resulting in a new steady state level that remained
      significantly higher than cholesterol esterase mRNA level in control rat
      pancreas. The feeding of high fat diet without cholesterol, or high cholesterol
      diet without high fat content, did not result in significant increase in
      pancreatic cholesterol esterase mRNA when compared to that observed in control
      chow-fed animals. The increase in cholesterol esterase mRNA after high fat/high
      cholesterol feeding paralleled the increased in pancreatic lipase mRNA. The high
      fat/high cholesterol-induced increase in cholesterol esterase mRNA was due to
      increase rate of transcription, as demonstrated by nuclear run-on assays.
      Additionally, in vitro incubation experiments of pancreatic lobules with
      [35S]methionine showed higher rates of 35S-labeled cholesterol esterase synthesis
      with lobules from the high fat/high cholesterol-fed animals. Taken together,
      these results demonstrated that high fat/high cholesterol diets increased
      cholesterol esterase mRNA level and enzyme biosynthesis in rat pancreas. The
      coordinated regulation of cholesterol esterase with another lipid digestive
      enzyme, the pancreatic lipase, suggested an important role for these proteins in
      dietary lipid absorption through the gastrointestinal tract.

PMID- 8138720
TI  - Role of endogenous lipid droplets in lipolysis in rat adipocytes.
AB  - Sonication of rat fat cells caused an increase in lipolysis in the absence of
      lipolytic stimulants (basal lipolysis) and loss of epinephrine responsiveness.
      Sonication of endogenous lipid droplets from fat cells also induced an increase
      in lipolysis in the presence of hormone-sensitive lipase (HSL) and loss of
      epinephrine responsiveness in a cell-free system consisting of lipid droplets and
      HSL. This increase in lipolysis was found not to be due to an increase in the
      surface area resulting from sonication, but seemed to be due to a decrease in the
      phosphatidylcholine concentration on the surface of the lipid droplets. Addition
      of phosphatidylcholine to the sonicated lipid droplets reduced the hydrolysis of
      triglyceride by HSL in the cell-free system, consisting of HSL and intact lipid
      droplets or a lipid emulsion containing phosphatidylcholine increased lipolysis.
      These results suggest that phosphatidylcholine on the surface of the lipid
      droplets may be a regulatory factor for lipolysis in fat cells.

PMID- 8138721
TI  - Synthesis of photoreactive phosphatidylethanolamine and its interaction with
      phospholipase A2.
AB  - A photoreactive derivative of phosphatidylethanolamine, N-(4
      azidobenzoyl)phosphatidylethanolamine (AB-PE), was synthesized by acylation of
      phosphatidylethanolamine with an N-hydroxysuccinimide ester of 4-azidobenzoic
      acid. The substantial photosensitivity exhibited by AB-PE correlated with a
      marked decrease in the absorption spectra of the compound. The compound proved
      sensitive to lipase and phospholipase A2 hydrolysis but resistant to
      phospholipase C and D activities. Photolysis of a sonicated dispersion of AB-PE
      containing phospholipase A2 resulted in irreversible inhibition of the enzyme.
      Addition of natural phosphatidylethanolamine provided protection against
      photoinactivation.

PMID- 8138722
TI  - Aberrant hypothalamic-pituitary-ovarian axis in the Watanabe heritable
      hyperlipidemic rabbit.
AB  - The WHHL rabbit has a defective low density lipoprotein receptor and is a model
      for familial hypercholesterolemia. WHHL rabbits are less fecund than NZW rabbits,
      the strain into which the defect has been inbred. This lower fecundity could be
      related to impaired ovarian steroidogenesis due to reduced intracellular
      availability of cholesterol. Here we compare the WHHL and NZW rabbits with regard
      to oocyte morphology and fertilization rates after stimulation with equine
      chorionic gonadotropin. We also compare hypothalamic-pituitary-ovarian axis
      function by measuring baseline and gonadotropin releasing hormone-stimulated
      plasma estradiol, progesterone, and gonadotropin levels, both before and after
      simvastatin inhibition of de novo cholesterol synthesis. WHHL rabbit oocytes
      remained encased in cumulus and had a lowered fertilization rate (9/50 vs. 83/87,
      P < 0.05). WHHL rabbits had lower baseline estradiol levels (7.1 +/- 0.72 vs.
      10.2 +/- 0.94, P < 0.05) and had higher baseline follicle stimulating hormone (P
      < 0.05) and luteinizing hormone (P < 0.05) levels. Simvastatin lowered luteal
      progesterone concentrations only in WHHL rabbits (P < 0.05). We conclude that the
      hypothalamic-pituitary-ovarian axis in WHHL rabbits is abnormal. The reduced
      availability of intracellular cholesterol for progesterone synthesis by
      inhibition of de novo cholesterol biosynthesis leads to a significant reduction
      in plasma progesterone concentrations in the WHHL. These findings have
      implications for women with familial hypercholesterolemia, particularly regarding
      treatment with inhibitors of de novo cholesterol synthesis.

PMID- 8138723
TI  - Phospholipid molecular species influence crystal habits and transition sequences
      of metastable intermediates during cholesterol crystallization from bile salt
      rich model bile.
AB  - Despite its importance in cholesterol gallstone formation, crystallization of
      cholesterol from bile is poorly understood, especially with respect to the
      influences of other biliary lipids. We reported recently (Konikoff et al. J.
      Clin. Invest. 1992. 90: 1155-1160) that cholesterol can crystallize from model
      and native biles as filamentous crystals covered by a surface layer of lecithin
      molecules. During growth, filamentous crystals transformed via metastable
      intermediates into classical plate-like cholesterol monohydrate crystals. Using
      the same dilute (1.2 g/dl total lipid) bile salt-rich (97.5 moles %) model bile
      supersaturated with cholesterol, we have studied the effects of natural egg yolk,
      soy bean as well as single molecular species of lecithins, other phospholipids
      and related lipid classes on early filamentous cholesterol crystallization, as
      well as transformations between crystal habits and their growth to equilibrium
      cholesterol monohydrate plates. After extraction and derivatization, HPLC
      analysis revealed that the surfaces of filamentous crystals were enriched
      preferentially with lecithin molecular species having longer and more saturated
      sn-1 and sn-2 acyl chains compared to mixed lecithin species of whole bile. In
      contrast, the molecular species distribution of lecithins on equilibrium plate
      like crystals resembled that of whole bile. After incubation of pre-formed
      anhydrous cholesterol and cholesterol monohydrate crystals in cholesterol-free
      lipid solutions, we demonstrated that surface-adsorbed lecithins were not
      preferentially enriched excluding nonspecific lecithin adsorption. Time-sequences
      and transformations between metastable crystalline intermediates were altered
      markedly by specific phospholipid species: model biles composed of saturated
      short-chain, medium-chain, and polyunsaturated long-chain lecithins induced rapid
      precipitation of short filamentous crystals that became plate-like slowly by an
      "arborization pattern." Long-chain saturated lecithins and natural sphingomyelins
      retarded cholesterol crystallization markedly, and filamentous as well as
      metastable intermediate crystals made transient appearances only after plate-like
      crystals had formed. These observations suggest that phospholipid molecular
      species and class influence the earliest events in cholesterol crystallization
      from bile salt-rich model bile. Furthermore, as the molecular species of
      lecithins adsorbed onto filamentous cholesterol crystals were more saturated than
      in whole bile and essentially identical to those in biliary vesicles, this
      finding provides chemical evidence for a vesicular origin of the critical
      cholesterol nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8138724
TI  - Development of unesterified cholesterol-rich lipid particles in atherosclerotic
      lesions of WHHL and cholesterol-fed NZW rabbits.
AB  - Previously, we isolated and characterized unesterified cholesterol-rich lipid
      particles (UCLP) that accumulate in extracellular spaces of atherosclerotic
      lesions of humans and cholesterol-fed rabbits. In the present study, we examined
      early developing atherosclerotic lesions to determine when UCLP appear and when
      they become enriched in cholesterol and sphingomyelin. Cholesterol-fed NZW
      rabbits, which rapidly develop atherosclerotic lesions, and genetically
      hyperlipidemic WHHL rabbits, which develop lesions over a longer period of time,
      were studied. UCLP of peak density 1.04 g/ml appear as early as 4 weeks after the
      onset of cholesterol feeding and progressively accumulate during atherosclerotic
      lesion development. Beginning with their appearance and afterwards, UCLP contain
      a saturating level (2:1 molar ratio) of cholesterol relative to phospholipid.
      Whereas, early UCLP are enriched in phosphatidylcholine, with time UCLP become
      enriched with sphingomyelin. Another UCLP population having a peak density of
      1.09 g/ml was present in control aortas and increased in amount more slowly than
      the d 1.04 g/ml UCLP during cholesterol feeding. The d 1.09 g/ml particles were
      predominantly unilamellar vesicles, the majority between 100 and 200 nm in
      diameter. They contained > 90% of their cholesterol in unesterified form and
      their ratio of unesterified cholesterol to phospholipid progressively increased
      from 0.6 to 1.7 during cholesterol feeding. Liposome resistance to solubilization
      by high density lipoproteins is known to be increased by enrichment with
      unesterified cholesterol and sphingomyelin. Sphingomyelin enrichment of
      unesterified cholesterol-rich lipid particles (UCLP) could stabilize cholesterol
      in a form that does not readily crystallize. However, at the same time, the early
      and progressive accumulation of UCLP in developing atherosclerotic lesions may
      limit reverse cholesterol transport and accelerate disease progression.

PMID- 8138725
TI  - Apolipoprotein B synthesis: a square lattice model.
AB  - We have formulated a random walk model for emerging apolipoprotein B interaction
      with its translocation channel on the surface of the rough endoplasmic reticulum
      based on the assumption that this interaction is a diffusion-mediated process.
      From this model, we found that a substantial proportion of mRNA-ribosome
      complexes was not bound to their translocation channels at any given moment of
      quasi-steady state. The duration of polypeptide chain elongation was an important
      determinant of the number of mRNA-ribosome complexes bound to their channels, but
      it had little net effect on the integrated rate of protein synthesis and
      translocation. The rates of protein synthesis and translocation for different
      secretory proteins that were cotranslationally translocated were very similar
      provided that they had similar mRNA concentration. We conclude that one of the
      control mechanisms regulating apolipoprotein B production may rely on the
      properties of translocation channels to determine the fate of newly synthesized
      apolipoprotein B molecules.

PMID- 8138726
TI  - Formation of cholesterol monohydrate crystals in macrophage-derived foam cells.
AB  - In a previous study using the J774 macrophage foam cells, we quantitated the
      accumulation of unesterified (free) cholesterol derived from cholesteryl ester
      hydrolysis in lysosomes, after phagocytic uptake of cholesteryl ester droplets.
      In the present study, we examined whether the accumulation of free cholesterol in
      lysosomes leads to the formation of cholesterol monohydrate crystals by analyzing
      the lipid composition of low density lysosome fractions isolated from cholesteryl
      ester-loaded macrophages after a 24-h incubation. Phase diagrams of the
      constituent lipids in the lipid-filled lysosomes predicted the formation of
      cholesterol monohydrate crystals. The formation of cholesterol monohydrate
      crystals was observed in cholesteryl ester-loaded macrophages after a 48-h
      incubation by polarizing light microscopy. The crystals had a density of 1.04
      g/ml and the morphology of cholesterol monohydrate crystals with an acute edge
      angle of about 80 degrees. The crystals appeared as needles as well as plates and
      melted only when heated to greater than 85 degrees C. The physical properties of
      these crystals are characteristic of cholesterol monohydrate. In our studies,
      crystal formation was observed even when cells had active acyl-CoA:cholesterol
      acyltransferase or when cholesterol efflux was stimulated. Electron microscopy
      and acid phosphatase cytochemistry of lysosomes in cholesteryl ester-loaded cells
      confirmed that cholesterol crystal formation occurred within lipid-loaded
      lysosomes. Time-lapse video microscopic studies revealed that most of the cells
      containing cholesterol monohydrate crystals not only remain viable but also have
      the capacity to translocate single crystals within cells. The data demonstrate
      that lysosomal accumulation of free cholesterol in macrophages after phagocytic
      uptake and hydrolysis of cholesteryl ester droplets leads to the formation of
      cholesterol monohydrate crystals within lipid-filled lysosomes. Such a process
      may lead to deposition of free cholesterol and cholesterol monohydrate crystals
      in macrophage foam cells during the progression of atherosclerosis.

PMID- 8138727
TI  - Report from the fourth annual meeting of the Chiropractic Research Journal
      Editors' Council.

PMID- 8138728
TI  - Videofluoroscopy in cervical spine trauma: an interinterpreter reliability study.
AB  - OBJECTIVE: The primary purpose of this study was to determine if, when confronted
      with a series of cervical videofluoroscopic (VF) studies, board certified
      radiologists who are trained in the interpretation of VF spinal examinations
      would be in agreement with one another with regard to the findings of normal,
      hypomobile or hypermobile intersegmental motion. As a secondary objective, we
      polled participating physicians regarding demographic issues such as time in
      practice, self-assessment of proficiency, the type of training received in VF
      interpretation and the number of VF studies read per year, in order to determine
      if any of these factors had any predictive value in terms of interexaminer
      agreement. DESIGN: Seven patients who had been exposed to cervical
      acceleration/deceleration (CAD) trauma from motor vehicle accidents were randomly
      selected from the practice of two of the authors (ACC and JSK). Three volunteers,
      who were asymptomatic and had no history of neck pain or injury to the neck, were
      also recruited. In all cases, informed consent was obtained in accordance with
      the Helsinki guidelines. Ten board qualified chiropractic radiologists were
      recruited to participate in this study. Blinded to the history and identity of
      the patients and volunteers, the participants were asked to view the 10 VF
      studies and, in each case, to report either "normal," "hypomobile" or "unable to
      determine" for all segments from OCC/C1 through C7/T1. The resulting data was
      analyzed for concordance using the kappa statistic. Kappa was calculated for all
      segments (OCC-T1) for agreement in "normal" vs. "abnormal" motion. The two
      possible choices for abnormal (i.e., hypermobility and hypomobility) were pooled
      together. We also compared the results of participants' responses to demographic
      questions with the results of their interpretations of the VF studies. SETTING:
      An urban group practice. Four of the patients were those of an orthopedist (ACC)
      and three were those of a general practitioner (JSK). PATIENT/OTHER PARTICIPANTS:
      Seven patients were randomly selected from a larger group of patients satisfying
      our selection criteria. Patients were chosen who had been exposed to CAD trauma
      and had been provided with at least 6 months of conservative chiropractic care,
      yet remained symptomatic as a result of their injuries. All had evidence of
      intersegmental instability in the cervical spine as defined by other
      investigators and none had any history of injury or pain in the cervical spine
      prior to their motor vehicle accident. Four males and three females with a mean
      age of 16 yr comprised the patient group. Two asymptomatic atraumatic volunteers
      were males and one was female. They were age matched to the patient group with a
      mean age of 38 yr. INTERVENTION: This study did not entail any form of
      intervention. MAIN OUTCOME MEASURES: Our primary outcome measure was that of
      concordance or agreement between our group of 10 participant radiologists in
      regard to their interpretations of the 10 VF studies provided to them, i.e., that
      of interinterpreter reliability. Higher values of kappa suggested that agreement
      between the radiologists was not likely due to chance alone. Our secondary
      outcome measure was a correlation between the results of our demographic
      questionnaires, completed by participating radiologists, and the overall
      interinterpreter reliability concordance. The hypothesis tested was that
      radiologists who have institutional training in VF, more years of experience, and
      those who read more VF studies annually and self-rank their proficiency as "high"
      are more likely to agree with others and/or are more likely to correctly analyze
      intersegmental motion than those whose training was less formal, and who have
      less experience, read fewer VF studies and self-rank their proficiency in reading
      VF as only "adequate" or lower. (ABSTRACT TRUNCATED)

PMID- 8138729
TI  - Patient benefits of attending a chiropractic low back wellness clinic.
AB  - OBJECTIVE: To demonstrate low back and/or leg pain patient reaction to attendance
      at a low back wellness school conducted to teach them how to control their back
      pain in daily living so as to reduce the incidence and severity of their problem.
      DESIGN: Sixty-one patients attending the clinic filled out a seven-question form
      that ranked their opinions of the class based on their feelings and reactions
      about it. SETTING: The private clinic of the author where a three-part back pain
      prevention clinic utilizing a slide lecture and patient participation was
      presented. PATIENTS: All suffered from low back and/or leg pain and were invited
      to attend at the time of their initial examination and report of findings.
      INTERVENTION: None. This is a patient questionnaire only. MAIN OUTCOME MEASURES:
      Immediately following the class, the patients were presented with a seven
      question form to answer. RESULT: A very positive acceptance of low-back wellness
      training is evidenced by 95% of the patients feeling it was worth their time to
      attend and feeling they learned something to prevent reinjury in daily living;
      100% felt it worth the doctor's time to present the class. CONCLUSION: Low back
      wellness school is a positive program from the patients' and doctor's viewpoints.

PMID- 8138730
TI  - Diagnosis and manipulative treatment in diabetic polyneuropathy and its relation
      to intertarsal joint dysfunction.
AB  - OBJECTIVE: To present the diagnosis and differential diagnosis of diabetic
      polyneuropathy and report a case in which a patient with this disorder was
      successfully managed utilizing chiropractic procedures. CLINICAL FEATURES: An 80
      year-old man with a history of diabetes mellitus complained of low back pain
      along with burning pains in the lower extremities and poor balance. Disturbance
      of vibration, joint position, coarse and fine touch and pinprick sensation was
      found along with extensive trophic changes, mild motor weakness and absent
      Achilles reflexes. Joint dysfunction was detected in the mortise and intertarsal
      joints and myofascial trigger points were found in the quadratus plantae muscles.
      INTERVENTION AND OUTCOME: The patient was treated with manipulation to the
      intertarsal and mortise joints and myofascial therapy to the quadratus plantae
      muscles 18 times over 4 months. This treatment brought about dramatic improvement
      in both symptoms and clinical signs of nerve function. CONCLUSIONS: It is
      possible that joint and/or myofascial dysfunction may play a role in the
      susceptibility to diabetic polyneuropathy and that treatment of these
      dysfunctional conditions may bring about improvement in the neuropathy. Possible
      mechanisms by which this may occur include impaired afferent stimulation from the
      intertarsal joint receptors due to loss of joint play and disturbance of
      axoplasmic flow along the nerves affected by the neuropathy. Reporting similar
      cases as well as conducting clinical trials with large populations may shed light
      on whether there is a relationship between diabetic polyneuropathy and joint and
      myofascial dysfunction of the feet.

PMID- 8138731
TI  - Multicentric reticulohistiocytosis (lipoid dermatoarthritis)
AB  - OBJECTIVE: To present a rare case of multicentric reticulohistiocytosis seen in a
      chiropractic office. CLINICAL FEATURES: A 64-yr-old female suffered from
      polyarthralgic manifestations of reticulonodular histiocytosis in skin nodules,
      mucous membrane and breast tissue. This later suddenly expanded to other joints
      in her body, leading her to seek medical care. INTERVENTION AND OUTCOME:
      Therapeutic acupuncture at major Meridian points along with gentle mobilization,
      soft tissue therapy and physical therapy modalities was instituted. Progress over
      a two year period gradually improved, though overall prognosis must be considered
      poor. CONCLUSION: Multicentric reticulohistiocytosis is an uncommon problem seen
      in the chiropractic office. Conservative care may help with symptomatology,
      though long term prognosis is poor.

PMID- 8138732
TI  - A histological investigation of human lower lumbar intervertebral canal (foramen)
      dimensions.
AB  - OBJECTIVE: To determine the proximity of neural structures to the boundaries of
      the interpedicular zone of the intervertebral canal in cadaveric adult human
      spines at the L4-5 and L5-S1 spinal levels. DESIGN: Nine randomly chosen blocks
      of human lumbosacral spinal tissues were processed for histological examination
      and mensuration of their left and right L4-5 and L5-S1 interpedicular zones of
      the intervertebral canals (foramina). Measurements of the important
      interpedicular zone were made using a computerized morphometry system to
      determine (i) the ratio between the cross-sectional area of the interpedicular
      zone canal and its large neural structure(s), (ii) the proximity of these neural
      structures to the boundary of the interpedicular zone, and (iii) the horizontal
      length of the interpedicular zone of the intervertebral canal. RESULTS: The mean
      cross-sectional area ratio of the interpedicular zone of the intervertebral canal
      to large neural structure(s) is 22.9 (SD 6.7)-30.8 (SD 4.4)% at the L4-5 level
      and 24.9 (SD 5.3)-31.1 (SD 5.3)% at L5-S1. The cross-sectional area of the
      interpedicular zone is 3.3 (SD 0.5)-4.8 (SD 1.7) times (X) larger than that of
      the large neural structures at the L4-5 level, and 3.3 (SD 0.6)-4.2 (SD 0.8) at
      the L5-S1 level. The mean minimum distance between the large neural structure(s)
      and the boundary of the interpedicular zone ranges from 0.4 (SD 0.4)-0.8 (SD 0.9)
      mm at the L4-5 level and from 0.4 (SD 0.4)-0.6 (SD 0.3) mm at the L5-S1 level.
      The horizontal length of the interpedicular zone of the intervertebral canal
      ranges from 8.2-12.2 mm. CONCLUSION: Within the interpedicular zone of the
      intervertebral canal, the minimum distance between neural structures and the
      boundary can be as little as 0.4 (SD 0.4) mm. The possible ramifications of this
      finding are discussed with regard to a previous gross anatomical study performed
      by Crelin (1973) that emphasized the anatomically and clinically less relevant
      lateral border of the intervertebral canal.

PMID- 8138733
TI  - Treating shoulder impingement using the supraspinatus synchronization exercise.
AB  - OBJECTIVE: More and more athletes are seeking care in the chiropractic office for
      athletic injuries. This article presents a case report of a young athletic
      patient suffering from bilateral shoulder pain-shoulder impingement and presents
      a review of the literature and a review of shoulder anatomy. This report
      introduces the supraspinatus synchronization exercise with discussion and
      illustrations. This patient was treated using the supraspinatus synchronization
      exercise. CLINICAL FEATURES: A 16-yr-old female was seen suffering from a 4-month
      history of shoulder pain. She was a competitive swimmer in high school athletics
      and the pain was made worse by swimming the backstroke. A clinical diagnosis of
      bilateral stage I impingement of the shoulder (Neer's classification) was made.
      INTERVENTION AND OUTCOME: The patient was given instructions on how to perform
      the supraspinatus synchronization exercise, conservative therapies including
      chiropractic manipulative therapy, ice, high-voltage electrical muscle
      stimulation and rehabilitation exercise band exercises were also used. The
      patient was treated for seven treatments over a 4-wk period with resolution of
      the condition. CONCLUSION: The shoulder is a very complex joint, and many authors
      discuss the necessity of smooth synchronous movement to keep it pain free without
      going into how one measures this synchronous movement. The case presented in this
      report responded quickly to conservative treatment using the supraspinatus
      synchronization exercise. A good well-designed clinical trial needs to be set up
      to check the efficacy of this exercise.

PMID- 8138734
TI  - Metaphysics, rationality and science.

PMID- 8138736
TI  - Commentary chiropractic scope of practice.

PMID- 8138735
TI  - Muscle scanning: the 18% solution.

PMID- 8138737
TI  - Quackery vs. accountability in the marketing of chiropractic.

PMID- 8138738
TI  - Concepts, comparisons, and controversies.

PMID- 8138739
TI  - Methodological and conceptual issues in health care system comparisons: Canada,
      Norway, and the United States.
AB  - There is a growing interest in comparison of international health care data with
      the hope that such studies will enable individual systems to learn from other
      systems. Such comparisons, however, presuppose that there exist common criteria
      for evaluating health care systems. The main thesis of this paper is that these
      comparative studies are misleading because they employ inappropriate
      operationalizations of these criteria because the operationalizations are based
      upon mistaken global conceptualizations of the criteria in question. The essay
      provides a methodological critique of what has been done and sets a new agenda
      for future research.

PMID- 8138740
TI  - Eppur si muove: a comment on Baruch Brody and Reider Lie.
AB  - The manuscript by Baruch Brody and Reider Lie presents a distorted image of cost
      comparisons and social accounts. They presuppose a static view of health systems.
      While there is methodological uncertainty in international comparisons, such
      uncertainty should not be used to justify a failure to act.

PMID- 8138741
TI  - The method of public morality versus the method of principlism.
AB  - Two years ago in two articles in a thematic issue of this journal the three of us
      engaged in a critique of principlism. In a subsequent issue, B. Andrew Lustig
      defended aspects of principlism we had criticized and argued against our own
      account of morality. Our reply to Lustig's critique is also in two parts,
      corresponding with his own. Our first part shows how Lustig's criticisms are
      seriously misdirected. Our second and philosophically more important part picks
      up on Lustig's challenge to us to show that our account of mortality is more
      adequate than principlism. In particular we show that recognition of mortality as
      public and systematic enables us to provide a far better description of morality
      than does principlism. This explains why we adopt the label "Dartmouth
      Descriptivism."

PMID- 8138742
TI  - Perseverations on a critical theme.
AB  - In response to my earlier critique of recent attempts to rebut principlism as an
      ethical approach, Green, Gert, and Clouser (GG&C) have in turn offered their own
      critique of my appraisal. This essay identifies eight major criticisms GG&C raise
      in their response and offers a rejoinder to each. Among them, three are
      especially important: (1) that the label of 'deductivism' fails to capture GG&C's
      ethical method and should be replaced by 'descriptivism'; (2) that pluralistic
      accounts, including principlism, fail to offer any systematic way to resolve
      moral conflicts; and (3) that appeals to broader 'moral' principles beyond the
      moral rules are deceiving, since apparent differences in 'moral' judgment
      invariably involve disagreement about empirical facts rather than further moral
      considerations. In response to (1), I defend my earlier label by emphasizing the
      stipulated and invariant status of the moral rules GG&C invoke, even as I
      question the adequacy of their putative 'descriptivism'. In response to (2), I
      suggest the plausibility of pluralist approaches and reiterate the modified just
      war criteria that Beauchamp and Childress invoke in situations when principles
      conflict. In response to (3), I suggest that a 'descriptivism' worthy of the name
      must systematically accommodate the appeal to moral principles that remains
      central to metaethical and normative discussions.

PMID- 8138743
TI  - ACTH stimulates melanogenesis in cultured human melanocytes.
AB  - While ACTH is known to induce skin pigmentation in man, its effects on cultured
      human melanocytes have not been investigated. Using a culture system free of
      artificial mitogens, we report for the first time that ACTH stimulates
      melanogenesis in cultured human melanocytes. While ACTH, alpha-MSH and the
      synthetic alpha-MSH analogue Nle4DPhe7 alpha-MSH all stimulate the activity of
      tyrosinase, the rate limiting enzyme in melanogenesis, and all produce a 50%
      increase in the melanin content of the cells at a concentration of 10(-8)-10(-7)
      mol/l, the shapes of the dose response curves differ: those for the MSH peptides
      are sigmoidal while those for ACTH are biphasic. In addition, human melanocytes
      are able to respond to concentrations of ACTH comparable with physiological
      plasma levels. We suggest that ACTH may be relatively more important than alpha
      MSH as a pigmentary hormone in man and could have a physiological role in skin
      pigmentation.

PMID- 8138744
TI  - The implications of insulin-like growth factor mRNA heterogeneity.

PMID- 8138745
TI  - Lipopolysaccharide modulation of eicosanoid and corticotrophin-releasing hormone
      release from rat hypothalamic explants and astrocyte cultures in vitro: evidence
      for the involvement of prostaglandin E2 but not prostaglandin F2 alpha and lack
      of effect of nerve growth factor.
AB  - Bacterial lipopolysaccharide (LPS) and prostaglandins (PG) E2 and F2 alpha are
      putative activators of the hypothalamo-pituitary-adrenal axis. Certain of the
      biological effects of LPS may be mediated by cytokines such as interleukin-1 beta
      (IL-1 beta), while IL-1 beta itself may operate via induction of the
      prostaglandins and/or nerve growth factor (NGF). As IL-1 beta stimulates the
      release of corticotrophin-releasing hormone (CRH) from acute rat hypothalamic
      explants directly, the effects of these substances on the release of CRH in vitro
      were investigated in short- and medium-term (20 and 60 min) incubations. The
      effect of LPS on the release of PGE2 and PGF2 alpha from these explants, as well
      as from cortical astrocyte cultures, was also studied. LPS did not modify the
      release of CRH, PGE2 or PGF2 alpha in 20-min incubations. In 60-min incubations,
      LPS stimulated the release of PGE2, whereas the release of CRH was weakly, but
      significantly, reduced; PGF2 alpha was not altered. PGE2 significantly stimulated
      CRH release in the 60-min but not in the 20-min experiments. This effect appeared
      to be selective for PGE2, since PGF2 alpha did not modify CRH release, alone or
      in combination. LPS also selectively released PGE2 but not PGF2 alpha from
      cortical astrocyte cultures after 24-h incubation. NGF had no effect on the
      release of explant CRH, regardless of the length of incubation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138746
TI  - Increased insulin receptor number and insulin responsiveness in a chicken
      hepatoma cell line.
AB  - Insulin receptor number and insulin responsiveness were compared in a chicken
      hepatoma cell line (LMH) and in normal chicken hepatocyte (cHep) cells cultured
      in the same conditions. LMH cells expressed two- to threefold more insulin
      receptors than cHep cells, without significant changes in affinity. The tyrosine
      kinase activity of solubilized and lectin (lentil+wheat germ agglutinin; WGA)
      purified LMH receptors was higher than that of cHep receptors. The ATP hydrolytic
      activity previously observed in WGA-purified receptors from chicken liver
      membranes was also present in WGA-purified receptors from cultured cHep cells.
      This unidentified membrane-associated ATPase was absent from LMH membrane
      solubilized material and therefore from WGA-purified LMH insulin receptors.
      Finally, LMH cells incorporated at least tenfold more amino isobutyric acid than
      cHep cells in the absence of insulin and were more responsive to insulin. The
      enhanced basal amino acid transport of LMH cells was most probably the
      consequence of their proliferative activity. The enhanced insulin responsiveness
      of LMH cells can be accounted for, at least in part, by one or several of the
      modifications presently demonstrated in LMH cells when compared with normal
      cultured hepatocytes: increased insulin receptor number and tyrosine kinase
      activity and possibly the loss of the membrane-associated ATPase.

PMID- 8138747
TI  - In vivo growth hormone gene expression in neonatal rat thymus and bone marrow.
AB  - The ontogenesis of GH gene expression in the pituitary gland and immune organs of
      rats was studied by in vitro amplification of GH mRNA using a specific reverse
      transcription-polymerase chain reaction. Samples were obtained after microsurgery
      and total RNA extraction of fetal, neonatal and adult rat tissues. Amplification
      was followed by analysis using Southern blot techniques and hybridization using a
      specific digoxigenin-labelled GH cDNA probe. The study was started on day 15 of
      gestation. GH gene expression occurred in the pituitary gland on day 17. GH mRNA
      was found in the bone marrow and thymus of neonatal rats but not in the spleen or
      liver. No GH transcripts were detected in the immune organs of fetal or adult
      rats. The transient GH expression in rat immune organs may indicate a specific
      function of GH in the development of the immune system during the neonatal
      period.

PMID- 8138748
TI  - Effects of dietary recombinant human insulin-like growth factor-I on
      concentrations of hormones and growth factors in the blood of newborn calves.
AB  - Colostrum is rich in insulin-like growth factor-I (IGF-I) and IGF-II and the
      dietary effects of recombinant human IGF-I (rhIGF-I) on the newborn are of
      interest. The objective of this study was to examine the effects of dietary rhIGF
      I upon selected hormones and growth factors in the blood. Calves were fed for the
      first 2 days of life with one of three experimental diets: (1) milk replacer plus
      isolated colostrum-derived globulin (MR-), (2) as (1) plus 98 mumol rhIGF-I/l
      (MR+) or (3) pooled cow colostrum. Thereafter, all animals received only milk
      replacer at 5% of body weight/feeding twice a day with only treatment 2 having
      the continued addition of 98 mumol rhIGF-I/l until completion of the experiment 7
      days after birth. Radioimmunoassays for insulin, prolactin, IGF-I, IGF-II, GH, L
      thyroxine, 3,5,3'-L-tri-iodothyroline and cortisol were conducted. With the
      exception of GH, all hormones and growth factors examined showed some form of
      dietary effect, but many were transient, changing only with the first feeding.
      Both insulin and prolactin concentrations exhibited a transient increase in blood
      at the first feeding, but insulin increased with the MR- treatment whereas
      prolactin increased with the MR+ treatment. Total IGF-I concentration in blood
      did not show any diet-induced changes for the first 4 days, but thereafter a rise
      in blood concentrations of IGF-I was observed. These data indirectly support the
      hypothesis that dietary IGF-I may be absorbed and causes transient systemic
      effects in the newborn calf.

PMID- 8138749
TI  - Low intrathyroidal iodine concentration in non-endemic human goitres: a
      consequence rather than a cause of autonomous goitre growth.
AB  - Iodine may have an inhibitory and, in some circumstances, a stimulatory effect on
      thyroid follicular cell growth. Exogenous iodine deficiency causes the growth of
      endemic goitres and it has been claimed that low intrathyroidal iodine stores
      stimulate growth. On the other hand, the role of iodine, if any, in regulating
      the growth of human nodular goitres exposed to an ample supply of iodine has not
      been studied systematically. Very few data on intrathyroidal iodine concentration
      in this type of goitre are available. In the present work we have investigated
      total iodine content in 24 samples from 11 clinically and histomorphologically
      well-defined fast and autonomously growing human nodular goitres from a non
      endemic area. Iodine was fractionated into thyroglobulin-iodine and non
      thyroglobulin-iodine. The regional distribution of intrathyroidal iodo-compounds
      was also assessed in three goitres. Total iodine concentration, as well as its
      sub-fractions, i.e. thyroglobulin-iodine and non-thyroglobulin-iodine, were
      significantly lower than in normal thyroids. Furthermore, there was large inter-
      and intraindividual heterogeneity of all iodo-compounds as well as of
      thyroglobulin. Total iodine concentration varied by a factor of almost 40 between
      different goitre samples and by a factor of 20 between samples taken from the
      same goitre. Total non-thyroglobulin-iodine, the only fraction comprising
      possible cell growth-regulating iodo-compounds, varied by a factor of > 60
      between different goitres and by a factor of > 6 between different samples of the
      same goitre. The low iodine concentration in all our goitre samples did not
      differ from values reported in the literature for endemic iodine-deficient
      goitres. Since all goitres studied here were actively growing while exposed to an
      ample supply of iodine, iodine shortage cannot be a primary and causal factor for
      the growth of this type of sporadic goitre. Rather, the low concentration and the
      large inter- and intraindividual heterogeneity of all iodo-compounds appear to be
      secondary incidental events well explained by the recently developed concept of
      autonomous thyroid growth.

PMID- 8138750
TI  - Effects of insulin-like growth factor-I peptides in rats with acute renal
      failure.
AB  - The effect of insulin-like growth factor-I (IGF-I) administration on body weight
      gain and the rate of recovery of renal function was investigated in rats
      following an acute episode of renal ischaemia. Since the des(1-3)IGF-I and LR3IGF
      I variant forms of IGF-I have been shown to be more potent than IGF-I, their
      effects were also examined. Acute renal failure was produced in male Sprague
      Dawley rats by clamping both renal arteries for 45 min. Treatment was commenced
      at the time of renal artery occlusion with vehicle (0.1 mol acetic acid/l;
      control group), IGF-I (2.0 mg/kg per day), des(1-3)IGF-I (2.0 mg/kg per day) or
      LR3IGF-I (1.5 mg/kg per day) by s.c. osmotic pump, and continued for 7 days, with
      rats being held in metabolism cages. Glomerular filtration rate (GFR) was
      estimated by the use of 51Cr-EDTA continuously infused i.p. via osmotic pump.
      Following the episode of renal ischaemia, body weight gain and nitrogen retention
      were significantly improved in all three peptide-treated groups, and serum urea
      concentrations were reduced in the groups treated with IGF-I and des(1-3)IGF-I.
      However, there was no evidence of the variants having any increased potency over
      the growth effects of IGF-I itself. GFR was significantly reduced, urine output
      was increased and urinary concentrating ability was reduced in all groups
      compared with normal rats, with no significant effect of the IGF peptides being
      apparent. A closer examination of the acute effects of LR3IGF-I on renal function
      was undertaken by measuring GFR for 3 days before and 3 days after renal
      ischaemia in two groups of rats, treated for the latter 3 days with either
      vehicle (controls) or LR3IGF-I (1.5 mg/kg per day). LR3IGF-I treatment following
      renal ischaemia resulted in a significantly greater fall in GFR than in controls,
      urinary osmolality was also significantly reduced, and fractional excretion of
      sodium was increased. In addition, there was histological evidence of a greater
      degree of tubular epithelial calcification in the kidneys of the rats treated
      with LR3IGF-I. This study showed that administration of IGF peptides at doses
      sufficient to cause significant improvement in anabolic status did not improve
      renal function in rats following an acute episode of renal ischaemia. Indeed the
      LR3IGF-I variant of IGF-I had a deleterious effect on renal function in the early
      stage of the recovery period.

PMID- 8138751
TI  - Structure-activity relationships of glucagon-like peptide-1(7-36)amide:
      insulinotropic activities in perfused rat pancreases, and receptor binding and
      cyclic AMP production in RINm5F cells.
AB  - To examine the structure-activity relationships in the insulinotropic activity of
      glucagon-like peptide-1(7-36) amide (GLP-1(7-36)amide), we synthesized 16
      analogues, including eight which were designed by amino acid substitutions at
      positions 10 (Alal0), 15 (Serl5), 16 (Try16), 17 (Arg17), 18 (Lys18), 21 (Gly21),
      27 (Lys27) and 31 (Asp31) of GLP-1(7-36)amide with an amino acid of GH-releasing
      factor possessing only slight insulinotropic activity, and three tentative
      antagonists including [Glu15]-GLP-1(8-36)amide. Their insulinotropic activities
      were assessed by rat pancreas perfusion experiments, and binding affinity to GLP
      1 receptors and stimulation of cyclic AMP (cAMP) production were evaluated using
      cultured RINm5F cells. Insulinotropic activity was estimated as GLP-1(7-36)amide
      = Tyr16 > Lys18, Lys27 > Gly21 > Asp31 >> Ser15, Arg17 > Ala10 >> GRF > [Glu15]
      GLP-1(8-36) amide. Displacement activity against 125I-labelled GLP-1(7-36)amide
      binding and stimulatory activity for cAMP production in RINm5F cells correlated
      well with their insulinotropic activity in perfused rat pancreases. These results
      demonstrate that (1) positions 10 (glycine), 15 (aspartic acid) and 17 (serine)
      in the amino acid sequence of GLP-1(7-36)amide, in addition to the N-terminal
      histidine, are essential for its insulinotropic activity through its binding to
      the receptor, (2) the amino acid sequences for the C-terminal half of GLP-1(7
      36)amide also contribute to its binding to the receptor, although they are less
      important compared with those of the N-terminal half, and (3) [Glu15]-GLP-1(8
      36)amide is not an antagonist of GLP-1(7-36)amide as opposed to des-His1 [Glu9]
      glucagon amide which is a potent glucagon antagonist.

PMID- 8138752
TI  - Circulating insulin-like growth factors-I and -II and substrates in fetal sheep
      following restriction of placental growth.
AB  - To determine the relationship between placental delivery of oxygen and glucose,
      circulating insulin-like growth factors (IGFs) and fetal growth, the effect of
      variable restriction of placental growth was determined in sheep in late
      gestation. Arterial blood was obtained via indwelling catheters at 120 and 127
      days of gestation, prior to necropsy at 130 days to measure fetal and placental
      weights. Plasma was acidified and subjected to size-exclusion high-performance
      liquid chromatography at pH 2.8 to dissociate and separate IGFs from their
      binding proteins. The acid-dissociated IGF fraction was analysed by sensitive and
      highly specific radioligand assays for IGF-I and IGF-II, previously defined using
      ovine IGFs. Fetal weight and blood pO2 and glucose at 120 and 127 days of
      gestation correlated positively with placental weight. Plasma IGF-I was
      positively associated with fetal weight and fetal liver weight, and with blood
      pO2 and glucose at both ages. Plasma IGF-II levels also correlated positively
      with fetal weight, fetal liver weight and with blood glucose and pO2, but only at
      127 days of gestation. In the most severely growth-retarded fetal sheep, blood
      glucose and pO2 and plasma IGF-I were significantly reduced when compared with
      normal fetuses at 120 days. All decreased further by 127 days of gestation as did
      plasma IGF-II in severely growth-retarded fetal sheep compared with normal
      fetuses. These observations are consistent with the hypothesis that both IGF-I
      and IGF-II are chronically regulated by oxygen and nutrition in utero and mediate
      part of the influence of placental supply of substrate over fetal growth.

PMID- 8138753
TI  - Post-transcriptional block in oxytocin gene expression within the seminiferous
      tubules of the bovine testis.
AB  - Northern blot hybridization showed that bovine and sheep testis, unlike testes
      from other mammals, contain moderate levels of an apparently normal oxytocin gene
      transcript. In situ hybridization localized this mRNA to within the seminiferous
      tubules, possibly in the Sertoli cells. Conflicting with this result,
      immunohistochemistry showed that both oxytocin and the syngeneic neurophysin I
      epitopes are both clearly restricted to the Leydig cells, being expressed here at
      a low level. Since illegitimate transcription from spurious start sites can lead
      to a lack of translation product, the integrity of the major ruminant testicular
      transcripts of the oxytocin gene was checked using differential hybridization.
      RNase protection and multiple polymerase chain reaction assays. All tests showed
      the transcripts to have a normal, translatable composition and to be transcribed
      from the conventional 5' initiation site. Therefore, the block in oxytocin gene
      expression within the tubules is probably due to a lesion at the post
      transcriptional level. The low level peptide expression in the Leydig cells can
      probably be attributed to the presence of functional transcripts in these cells,
      which are below the level of significant detection for the in situ hybridization
      assay.

PMID- 8138754
TI  - Control of superoxide dismutase, catalase and glutathione peroxidase activities
      in rat lymphoid organs by thyroid hormones.
AB  - This study examined the effect of experimental hyper- and hypothyroidism on the
      superoxide dismutase, catalase and glutathione peroxidase activities of rat
      lymphoid organs (mesenteric lymph nodes, spleen and thymus) and muscles (soleus
      and gastrocnemius-white portion) for comparison. The capacity for the generation
      of reducing equivalents was also investigated: activities of glucose-6-phosphate
      dehydrogenase (pentose-phosphate pathway) and citrate synthase (Krebs cycle).
      Hyperthyroidism tended to enhance lipid peroxide content in all tissues. This
      effect may result from (1) a high capacity for the generation of reducing
      equivalents in cytosol and mitochondria and (2) a reduced activity of catalase in
      the lymphoid organs and of glutathione peroxidase in the muscles. The process of
      lipid peroxidation in these tissues caused by hyperthyroidism was probably slowed
      down by the augmentation of CuZn- and Mn-superoxide dismutase (Mn-SOD) activities
      observed under this condition. Hypothyroidism tended to diminish lipid
      peroxidation and did not affect citrate synthase and glucose-6-phosphate
      dehydrogenase activities in the lymphoid organs and muscles. Low levels of
      thyroid hormones tended to diminish Mn-SOD and glutathione peroxidase activities.
      These findings show that the thyroid hormones might be able to regulate the
      activities of CuZn- and Mn-SOD, and catalase and glutathione peroxidase in the
      lymphoid organs and skeletal muscles.

PMID- 8138755
TI  - Changes in fetal thyroid hormone levels in adrenalectomized fetal sheep following
      continuous cortisol infusion 72 h before delivery.
AB  - Continuous infusion of cortisol into adrenalectomized fetal sheep during the last
      72 h of gestation (term = 145 +/- 2 days) produced a significant (P < 0.05) rise
      in fetal serum tri-iodothyronine (T3) mean +/- S.E.M. concentrations from 398 +/-
      65 to 1340 +/- 238 ng/l. A concurrent decrease in plasma thyroxine (T4) levels
      was observed in three out of four animals. No significant changes in the
      concentrations of either hormone were noted prior to the start of cortisol
      infusion. The plasma concentrations of cortisol, T3 and T4 at term were similar
      to those in untreated full-term lambs. Adrenalectomized fetuses not given
      cortisol infusions still had low levels of T3 at term, with no increase being
      observed. The results suggest that cortisol plays an important role in the
      increase of fetal plasma T3 observed towards the end of gestation. This is
      probably achieved by the stimulation of the monodeiodination of T4 to T3 in the
      peripheral tissues.

PMID- 8138756
TI  - Role of endogenous atrial natriuretic peptide in volume expansion diuresis and
      natriuresis of the Pekin duck.
AB  - Polyclonal antibodies raised in a rabbit against avian atrial natriuretic peptide
      (ANP) were shown to reduce circulating endogenous ANP levels in Pekin ducks by
      more than 90%, and were subsequently used to investigate the role of this peptide
      in volume expansion diuresis and natriuresis. Conscious birds, undergoing a
      steady-state diuresis and natriuresis maintained by an i.v. infusion of hypotonic
      saline at a rate of 0.7 ml/min, responded to ANP antiserum (anti-ANP) with an
      immediate 30% reduction in urine flow rate and sodium excretion which lasted for
      about 30 min. Plasma arginine vasotocin levels were not changed by anti-ANP
      whereas circulating angiotensin II concentrations increased immediately following
      the administration of anti-ANP. Serum from non-immunized normal rabbits produced
      no changes in the renal and plasma parameters monitored. The results show that
      the high circulating levels of endogenous ANP associated with volume expansion
      promote renal salt and fluid excretion and thus have a major physiological role
      in avian volume homeostasis.

PMID- 8138758
TI  - The philosophical foundations of public health: an invitation to debate.

PMID- 8138757
TI  - A modulatory role of endogenous opioids on prolactin secretion at the end of
      pregnancy in the rat.
AB  - It is well known that the fall in serum progesterone concentrations during late
      pregnancy induces prolactin secretion in rats. On day 19 of pregnancy,
      administration of 10 mg of the antiprogesterone RU-486/kg induced a small but
      significant increase in serum prolactin. A lower dose (2 mg/kg) was not
      effective. Administration of naloxone (2 mg/kg) to pregnant rats on day 19 of
      pregnancy did not modify circulating prolactin but, after RU-486 treatment, a
      notable increase in serum prolactin was obtained 30 min after naloxone was given.
      The lack of effect of naloxone-methobromide in pregnant rats pretreated with RU
      486 may indicate that the opioid-induced prolactin suppression acts centrally,
      most probably at the hypothalamic level. During day 21 of pregnancy, the time
      course of prolactin secretion, measured at 0900, 1400, 1900 and 2200 h, was
      inversely correlated with circulating progesterone levels. At 0900 h, serum
      prolactin was very low with high serum progesterone concentrations but a
      significant increase in serum prolactin occurred at 2200 h; this was coincident
      with a significant decrease in the steroid. The stimulatory effect of naloxone on
      prolactin secretion was clearly dependent on the circulating progesterone level.
      Thus, at 1900 h of day 21, naloxone induced a significant increase in serum
      prolactin but, at 2200 h, the opioid antagonist dramatically enhanced the
      circulating level of prolactin. The serum prolactin increase induced by naloxone
      at 1900 h was prevented by the s.c. administration of 5 mg progesterone given 7 h
      earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138759
TI  - Collaborative Registry of Smoking Cessation Trials.

PMID- 8138760
TI  - Neural tube defects in Newfoundland.

PMID- 8138761
TI  - Longitudinal and cross sectional mortality studies in injecting drug-users.

PMID- 8138762
TI  - Health and health care of rural populations in the UK: is it better or worse?
AB  - OBJECTIVE--To review available evidence on the problems facing rural health care
      in the UK. In particular, to determine whether the health of rural populations is
      worse than that of town dwellers and how the quality of health care is influenced
      by rurality. CRITERIA FOR INCLUSION AND EXCLUSION OF ARTICLES--A wide variety of
      publications and data sources were used. A number of computerised databases with
      different specialisations (for example medical, health care management) were used
      to identify relevant published articles. In addition, reports, reviews, and
      surveys produced by agencies for local circulation were identified by approaching
      academic, service, and voluntary bodies thought likely to have an interest in
      rural health. Although this "grey" literature is not subject to peer review, the
      relative lack of relevant UK publications made it a useful data source for
      illustrative purposes. Similarly, published articles based on rural health in
      other developed countries were used when UK data were lacking. CONCLUSIONS-
      Although the evidence concerning the health and health care of the UK rural
      populations is suggestive, it is very general and further research is needed.
      Levels of urban health seem to be generally worse than in rural areas, but
      contradictions do exist. The evidence on quality of care suggests that service
      accessibility is a central problem, and rural populations have poorer access than
      others. Within rural populations, such disadvantage is not uniformly experienced-
      it affects some groups more than others. In addition, the NHS does not seem to
      have a consistent policy about whether rurality should influence resource
      allocation, and how it should be incorporated.

PMID- 8138763
TI  - Randomised controlled trial in northern England of the effect of a person knowing
      their own serum cholesterol concentration.
AB  - SUBJECT OBJECTIVE: To test the hypotheses that the knowledge that the serum
      cholesterol concentration is raised (> or = 6.5 mmol/l) will lead to a reduction
      in the concentration after education intervention and that the knowledge that the
      concentration is not raised does not lead to an increase in the serum cholesterol
      concentration after education intervention. DESIGN: Prospective randomised trial,
      with investigators blind to the randomisation. SETTING: An industrial site in
      Manchester, England. PARTICIPANTS: A total of 495 employees of Imperial Chemical
      Industries, 469 of whom completed the trial. MAIN RESULT: There was a significant
      reduction in the serum cholesterol concentration of those whose initial
      concentration was > or = 6.5 mmol/l and who were given the result. This reduction
      was 0.28 mmol/l greater than in the control group. The reduction was similar,
      however, to the increase in the serum cholesterol concentration in those whose
      initial concentration was < 5.2 mmol/l, regardless of whether or not they had
      been given the result. CONCLUSION: These results support the hypotheses, although
      the lack of regression to the mean in the control group with high serum
      cholesterol suggests that this conclusion should be treated with caution.

PMID- 8138764
TI  - Demographic and dietary profiles of high and low fat consumers in Australia.
AB  - STUDY OBJECTIVE: To determine the socio-demographic, attitudinal, and dietary
      correlates of high and low fat consumption in the community. DESIGN: The study
      was undertaken using a postal survey format. A questionnaire was sent for self
      completion to a randomised sample of the adult population of two Australian
      states. PARTICIPANTS: Adult participants were selected randomly from the
      Electoral Rolls of the states of Victoria and South Australia. As voting at
      elections is compulsory in Australia, these rolls contain the names of all
      Australian citizens over the age of 18 years. Altogether 3209 respondents
      completed the survey giving a response rate of 67%. MAIN RESULTS: Lower than
      average fat consumption was more common in women. Age was a significant factor
      only in men. Occupation was not related to lower than average fat consumption but
      manual work and low occupational prestige were linked to higher than average
      consumption in men. People with a history of conditions related to heart disease
      were more likely to be low consumers but medical history did not distinguish high
      from average consumers. Low fat consumption was linked to higher refined and
      natural sugar consumption and higher alcohol consumption, but protein and complex
      carbohydrate consumption did not vary with fat consumption. Low fat diets also
      had higher densities of fibre and most vitamins and minerals, the exceptions
      being retinol, zinc, and vitamin B12, nutrients generally linked to meat and
      dairy consumption. Of the latter, only the low zinc concentrations, which are
      already borderline in the community, pose a potential nutritional problem.
      CONCLUSIONS: This study showed very strong links between dietary fat intake and
      the intake of nearly all other nutrients in the diet. The results highlight the
      need to consider relationships between nutrients not only for purposes of
      nutrition education but also in relation to nutritional epidemiology studies.

PMID- 8138765
TI  - Recurrence of acute otitis media at preschool age in Sweden.
AB  - STUDY OBJECTIVE: The probability of recurrence of acute otitis media during the
      preschool years was investigated. SETTING: All children born in a semirural
      Swedish municipality were followed up from birth to their 7th birthday. DESIGN:
      Information about visits to physicians for acute otitis media was collected
      retrospectively at all primary health care centres and at paediatric and ear,
      nose, and throat departments. Check up visits after acute otitis media were
      excluded. Life table methods were used for analyses. PARTICIPANTS: All 1306
      children born in the study municipality between 1977 and 1981 were included.
      Children who moved from the study area during the follow up years (24%) were
      included in the analyses from the date of birth to the date they left the area.
      MAIN RESULTS: At age 3 years, 38%, 10%, and 4% of the children had made at least
      one, three, and five visits respectively to a physician because of acute otitis
      media. By their 7th birthday, 61%, 24%, 12%, and 2% of the children had made at
      least one, three, five, and 10 visits respectively to a physician because of this
      disorder. CONCLUSIONS: A strong association was found between the number of
      visits made for acute otitis media during the first year of life and the
      probability of visiting a physician because of this disorder over the next 12
      months.

PMID- 8138766
TI  - Smoking and drinking habits before and during pregnancy in Spanish women.
AB  - STUDY OBJECTIVE: To investigate possible changes in smoking and drinking habits
      during pregnancy and to elucidate the sociodemographic factors associated with
      these changes in Spanish women. DESIGN: A cross-sectional survey. PARTICIPANTS
      AND SETTING: A total of 1004 pregnant women of between 12 and 18 weeks of
      gestation who were attending the antenatal clinic of the main regional hospital
      of Valencia (Spain) during 1989 were studied. All participants completed the
      study and only one eligible woman refused to participate when approached.
      MEASUREMENTS AND MAIN RESULTS: Information was obtained by structured
      questionnaire (Euromac questionnaire), which included items on age, educational
      level, marital status, occupation, parity, previous and present smoking habits,
      and previous and present alcohol consumption. Women were asked about the
      consumption of cigarettes and alcohol for a typical week before they knew they
      were pregnant, and details of current consumption were obtained for the week
      before the interview. The number of drinks taken per week was later converted to
      the amount of absolute alcohol (in g). Sixty per cent of the women smoked and 72%
      drank alcohol before pregnancy. Forty eight per cent of smokers stopped smoking
      and 37% of drinkers stopped drinking alcohol during pregnancy. No
      sociodemographic factor showed an independent association with either smoking or
      drinking cessation. Only the number of cigarettes and the amount of alcohol
      consumed before pregnancy were identified as significant independent predictors
      for stopping. CONCLUSIONS: Pregnant Spanish women seemed to stop smoking at about
      three times the rate found in Spanish women in the reproductive years. The
      sociodemographic variables usually associated with stopping smoking could not
      account for the high rate of quitting in these Spanish women, a rate higher than
      that in women from other developed countries. The high prevalence of smoking
      before pregnancy might explain not only the high rate of stopping smoking but
      also the absence of a well defined profile of "quitters". In our study, high
      levels of alcohol consumption were limited to a small group of pregnant women,
      and preventive efforts should be focused on this group.

PMID- 8138767
TI  - Two classes of creativity--improving systematic reviews.

PMID- 8138768
TI  - An outbreak of illness among schoolchildren in London: toxic poisoning not mass
      hysteria.
AB  - STUDY OBJECTIVE: To determine the cause of an outbreak of acute gastrointestinal
      illness that occurred shortly after lunch in children attending a school in
      London, UK. DESIGN: A questionnaire survey of children at the affected school was
      carried out on the day after the incident. Microbiological, environmental, and
      toxicological investigations were also undertaken. SETTING: A school in London,
      UK. PARTICIPANTS: Altogether 374/468 (80%) of the children who had eaten lunch at
      the school on the day of the incident completed a questionnaire. MAIN RESULTS:
      There was a significant association between illness and the consumption of raw
      cucumber (relative risk = 6.1; 95% confidence interval 2.2, 16). Microbiological
      investigation of the foods served at lunch did not show any pathogens and
      toxicological investigations suggested that the cucumbers were contaminated by a
      pesticide. CONCLUSIONS: Although the outbreak displayed several typical features
      of mass psychogenic illness, the most probable cause was a toxic chemical present
      in cucumber served at lunch. Those responsible for investigating outbreaks of
      illness should be aware of the possible toxicological causes and the appropriate
      modes of investigation. They should be wary of too readily attributing a
      psychogenic cause to unusual outbreaks of acute illness in schoolchildren.

PMID- 8138769
TI  - Three year follow up study of national influenza vaccination practices in Japan.
AB  - STUDY OBJECTIVE: To evaluate new national influenza vaccination practices which
      were started in 1987 under a revised law in Japan. DESIGN: This was a three year,
      nonrandomised cohort study with information collected by questionnaire between
      1989 and 1991. SETTING: Eight primary schools in the city of Yonago, Tottori,
      Japan. These schools were selected from 23 schools in the city. PARTICIPANTS:
      Altogether 4251 pupils (1355 boys and 2896 girls) in years 1-4 of the eight
      primary schools were included in this study, and followed up. Three years later,
      data for 1619 pupils (768 boys and 851 girls) were obtained and analysed. MAIN
      RESULTS: The one-winter seasonal incidence rates of influenza-like disease were
      13.4%, 29.9%, and 10.3% in 1989, 1990, and 1991 respectively. The incidence rate
      of influenza-like disease in fully vaccinated pupils was significantly lower than
      that in unvaccinated pupils in 1990, but not in 1989 or 1991. Stepwise multiple
      regression analysis showed that the incidence of influenza-like disease had a
      statistical relationship with the frequency of vaccination and the school year
      (R2 was 0.0148). Standardised parameters of the frequency of vaccination and the
      school frequency of vaccination and the school year were -0.089 and -0.080
      respectively. CONCLUSIONS: The preventive effects of influenza vaccine are not
      strong. There must be some unknown factors that affect the incidence of
      influenza. This vaccine is useful for pupils in the early school years who seem
      to have less resistance. All pupils should not be inoculated with the vaccine to
      reduce influenza transmission in the community or school.

PMID- 8138770
TI  - Why don't more young men in the UK become fathers?
AB  - OBJECTIVE: This paper aims to show that, compared with young women, there is an
      apparent discrepancy in the reported sexual behaviour of young men and records of
      their fatherhood. DESIGN: The data come from four studies of the sexual behaviour
      of young people in various parts of Britain between 1960 and 1990 and from
      statistics published by the Office of Population Censuses and Surveys. MAIN
      RESULTS: More of the young men than the young women had been sexually active, and
      the men had had more sexual partners. Relatively few men under 20, however, are
      identified as fathers. In 1991 there were 52,396 live births to women under 20
      years, but only 12,959 births were attributed to men under 20, and if all those
      to women under 20 for which the father was not identified are added to this, the
      total is still only 28,208--54% of the number of births to women of that age.
      Seven possible reasons for the discrepancy are discussed. Data suggest that the
      two most probable explanations are that there are different patterns of
      intercourse among young men and women and that the data obtained in surveys are
      to some extent inaccurate or biased. CONCLUSIONS: Differing behaviours indicate a
      double standard for men and women. Imperfect information affects predictions
      about a potential heterosexual HIV epidemic.

PMID- 8138771
TI  - HIV surveillance by testing saliva from injecting drug users: a national study in
      New Zealand.
AB  - OBJECTIVE: To determine whether the prevalence of HIV infection among injecting
      drug users in New Zealand has remained low since the introduction of a needle and
      syringe exchange scheme in May 1988. DESIGN: Anonymous survey of intravenous drug
      users attending outlets of the exchange scheme, based on questionnaires and
      saliva testing. SETTING: Twelve pharmacies and community outreach organisation in
      six cities. SUBJECTS: Altogether 620 people provided saliva specimens and
      completed questionnaires. These represented 73% of those who visited exchange
      scheme outlets during a three month period in 1992. MAIN OUTCOME MEASURE: Saliva
      was tested for antibodies to HIV-1 and HIV-2 using an IgG-capture enzyme linked
      immunosorbent assay (GACELISA). RESULTS: Of 591 specimens eligible for inclusion,
      only three (0.5%) were repeatedly reactive in the GACELISA test, while two of
      these were also positive in a Western blot test. CONCLUSIONS: Although surveys
      show that sharing of needles and syringes was common in New Zealand until
      recently, the prevalence of HIV infection in intravenous drug users has remained
      low. This can probably be attributed to the success of educational campaigns and
      legislative action to allow a needle and syringe exchange scheme to be set up.

PMID- 8138772
TI  - The Cochrane Lecture. The best and the enemy of the good: randomised controlled
      trials, uncertainty, and assessing the role of patient choice in medical decision
      making.
AB  - This lecture aimed to create a bridge to span the conceptual and ideological gap
      between randomised controlled trials and systematic observational comparisons and
      to reduce unwanted and unproductive polarisation. The argument, simply put, is
      that since randomisation alone eliminates the selection effect of therapeutic
      decision making, anything short of randomisation to attribute cause to consequent
      outcome is a waste of time. If observational comparison does have any significant
      part in evaluating medical outcomes, there is a grave danger of "the best", to
      paraphrase Voltaire, becoming "the enemy of the good". The first section aims to
      emphasise the advantages of randomised controlled trials. Then the nature of an
      essential precondition--medical uncertainty--is discussed in terms of its extent
      and effect. Next, the role of patient choice in medical decision making is
      considered, both when outcomes can safely be attributed to treatment choice and
      when they cannot. There may be many important situations in which choice itself
      affects outcome and this could mean that random comparisons give biased estimates
      of true therapeutic effects. In the penultimate section, the implications of this
      possibility both for randomised controlled trials and for outcome research is
      pursued and lastly there are some simple recommendations for reliable outcome
      research.

PMID- 8138773
TI  - Prospective study of predictors of attendance for breast screening in inner
      London.
AB  - OBJECTIVE: To investigate the predictors of first-round attendance for breast
      screening in an inner city area. DESIGN: Prospective design in which women were
      interviewed or completed a postal questionnaire before being sent their
      invitation for breast screening. Sociodemographic factors, health behaviours, and
      attitudes, beliefs, and intentions were used as predictors of subsequent
      attendance. A randomised control group was included to assess the effect of being
      interviewed on attendance. SETTING: Three neighbouring health districts in inner
      south east London. PARTICIPANTS: A total of 3291 women aged 50-64 years who were
      due to be called for breast screening for the first time. The analysis of
      predictors was based on a subsample of 1301, reflecting a response rate of 75% to
      interview and 36% to postal questionnaire. MAIN RESULTS: Attendance was 42%
      overall, and 70% in those who gave an interview or returned a questionnaire.
      There was little evidence for an interview effect on attendance. The main
      findings from the analysis of predictors are listed below. (These were
      necessarily based on those women who responded to interview/questionnaire and so
      may not be generalisable to the full sample.) (1) Sociodemographic factors: Women
      in rented accommodation were less likely to go for screening but other indicators
      of social class and education were not predictive of attendance. Age and other
      risk factors for breast cancer were unrelated to attendance, as was the distance
      between home and the screening centre. Married or single women were more likely
      to attend than divorced, separated, or widowed women, and black women had a
      higher than average attendance rate; however, neither of these relationships was
      found in the interview sample. (2) Health behaviours: Attenders were less likely
      to have had a recent breast screen, more likely to have had a cervical smear,
      more likely to go to the dentist for check ups, and differed from non-attenders
      with regard to drinking frequency. Exercise, smoking, diet change, and breast
      self-examination were unrelated to attendance. (3) Attitudes, beliefs, and
      intentions: The two best predictors were measures of the perceived importance of
      regular screening for cervical and breast cancer and intentions to go for breast
      screening. Also predictive were beliefs about the following: the personal
      consequences of going for breast screening, the effectiveness of breast
      screening, the chances of getting breast cancer, and the attitudes of significant
      others (the woman's husband/partner and children). Women who reported a moderate
      amount of worry about breast cancer were more likely to attend than those at the
      two extremes. CONCLUSIONS: Attenders and non-attenders differ in two broad areas:
      the health related behaviours they engage in and the attitudes, beliefs, and
      intentions they have towards breast cancer and breast screening. The latter are
      potentially amenable to change, and though different factors may operate among
      women who do not respond to questionnaires, the findings offer hope that
      attendance rates can be improved by targeting the relevant attitudes and beliefs.
      This could be done by changing the invitation letter and its accompanying
      literature, through national and local publicity campaigns, and by advice given
      by GPs, practice nurses, and other health professionals. It is essential that
      such interventions are properly evaluated, preferably in randomised controlled
      studies.

PMID- 8138774
TI  - Is use of hospital services a proxy for morbidity? A small area comparison of the
      prevalence of arthritis, depression, dyspepsia, obesity, and respiratory disease
      with inpatient admission rates for these disorders in England.
AB  - OBJECTIVES: To examine the relationship between specific types of morbidity,
      measured by validated survey questions, and hospital service use and mortality to
      see if the latter two could act as a proxy in health needs assessment, health
      service planning, and resource allocation in a typical health district. DESIGN: A
      postal questionnaire was used to provide information about depression, digestive
      disorders, musculo-skeletal disorders, obesity, respiratory disease, and hip and
      knee pain. The questions were from survey instruments that have been widely used
      to derive information about these conditions. The relationships between the
      prevalence of these specific types of morbidity and appropriate admission and
      mortality rates were explored using linear regression and Pearson correlation
      analysis. SETTING: The population of Rotherham health district, England.
      SUBJECTS: A simple random sample of the residents of each of the 22 electoral
      wards in Rotherham health district. RESULTS: Responses were obtained from 78% of
      the 5000 sampled (82% after excluding people who had moved house or died).
      Significant, positive correlations were found between the prevalence of
      respiratory disease and the hospital admission and mortality rates for
      respiratory problems (r = 0.68, p < 0.01 and r = 0.54, p < 0.01) and the
      prevalence of depression and the admission rate for depression (r = 0.52, p <
      0.05). No such relations were found for digestive disease, musculo-skeletal
      disease, and obesity. For the conditions examined here, hospital service use was
      a more useful measure than mortality. CONCLUSIONS: Only two diseases (respiratory
      disease and depression) out of the seven diseases or procedures investigated
      showed a positive correlation between hospital admission and disease prevalence.
      But even for these two, the correlations explained less than 50% of the variance.
      Caution must be exercised when hospital service use is being considered as a
      proxy for morbidity.

PMID- 8138775
TI  - Epidemiology and causation: a realist view.
AB  - In this paper the controversy over how to decide whether associations between
      factors and diseases are causal is placed within a description of the public
      health and scientific relevance of epidemiology. It is argued that the rise in
      popularity of the Popperian view of science, together with a perception of the
      aims of epidemiology as being to identify appropriate public health
      interventions, have focussed this debate on unresolved questions of inferential
      logic, leaving largely unanalysed the notions of causation and of disease at the
      ontological level. A realist ontology of causation of disease and pathogenesis is
      constructed within the framework of "scientific materialism", and is shown to
      provide a coherent basis from which to decide causes and to deal with problems of
      confounding and interaction in epidemiological research. It is argued that a
      realist analysis identifies a richer role for epidemiology as an integral part of
      an ontologically unified medical science. It is this unified medical science as a
      whole rather than epidemiological observation or experiment which decides causes
      and, in turn, provides a key element to the foundations of rational public health
      decision making.

PMID- 8138776
TI  - Measuring health status in the community: a comparison of methods.
AB  - STUDY OBJECTIVE--The measurement of health outcomes is central to the evaluation
      of medical treatment and intervention. It is generally acknowledged that such
      measurement ought to include an assessment of the impact of health care on the
      quality of life, as well as its quantity. The Health Measurement Questionnaire
      (HMQ) was developed as a means of identifying respondents in terms of Rosser's
      classification of illness states. This study examines the extent of convergent
      validity of the HMQ when used as a self report measure of health status,
      alongside the General Health Questionnaire (GHQ) and the Nottingham Health
      Profile (NHP). DESIGN--A randomised survey of residents of Wolverhampton was
      drawn from the electoral register. Interviews were conducted in the respondents'
      own homes. The three measurement instruments formed part of an extensive battery
      of questionnaires aimed at assessing a broad range of health issues. PARTICIPANTS
      -A total of 430 respondents were interviewed, of whom 407 completed the HMQ.
      Altogether 210 also completed the GHQ, and a further 207 completed the NHP.
      Failure in the interview protocol meant that 12 respondents did not complete
      either the GHQ or the NHP; these respondents did complete their HMQ. MEASUREMENTS
      AND MAIN RESULTS--At the descriptive level, Rosser distress categories derived
      from the HMQ seem to correlate well with the GHQ. There is a strong association
      between weighted Rosser disability/distress states and scores produced using the
      NHP. All three measures discriminated between "healthy" and "not healthy"
      subgroups of respondents. CONCLUSIONS--The results indicate strong evidence for
      convergent validity. There are significant levels of physical and psychological
      morbidity within the community. The results of this study reinforce the case for
      the continued measurement of health status within the general population. Low
      cost techniques such as the HMQ offer the prospect of such measurement.

PMID- 8138777
TI  - General practitioner notes as a source of information for case-control studies in
      young women. UK National Case-Control Study Group.
AB  - STUDY OBJECTIVE: The UK National Case-Control Study was carried out to
      investigate the relationship between oral contraceptive use and breast cancer
      risk. This study investigates whether general practitioner notes could be used as
      the sole data source for epidemiological studies of young women and what the
      effect would be on non-response and recall bias. DESIGN: Case-control study with
      data on gynaecological, obstetric, and contraceptive history collected at
      interview and from general practitioners' notes. Information from these two
      sources was compared. SETTING: This was a population-based study. PARTICIPANTS:
      Altogether 755 women with breast cancer aged under 36 years at diagnosis, each
      with an age-matched control, participated in the study. Response rates at
      interview were 72% and 89% for cases and controls but GP data were available for
      90% of the 1049 case and first-selected control pairs. MAIN RESULTS: There was
      generally good agreement between the two data sources with respect to obstetric
      history and gynaecological procedures (hysterectomy, oophorectomy, and tubal
      ligation). The use of intra-uterine devices, or diaphragm, and partner's
      vasectomy were not reliably recorded in the GP's notes. The overall results of
      the UK study would have been qualitatively the same with respect to the
      relationship between oral contraceptive use and breast cancer risk if GP notes
      only had been used, in spite of the fact that only about half of all oral
      contraceptive usage was recorded in the notes. Response rates would have been
      higher, recall bias eliminated, and the cost of the study halved. CONCLUSIONS:
      When planning case-control studies in young women, the possibility of using GP
      notes as the primary data source should be considered. Lack of data on potential
      confounding factors is a possible drawback to such use. The practice of
      destroying GP's notes shortly after the death of patients seriously restricts the
      possibility of using these notes when studying rapidly fatal conditions.

PMID- 8138778
TI  - Spatiotemporal boundary formation: boundary, form, and motion perception from
      transformations of surface elements.
AB  - Continuous surface boundaries, object shape, and global motion can be perceived
      from information that is fragmentary in both space and time. The authors report
      investigations indicating that accretion and deletion of texture is only 1 member
      of a broader class of element transformations that produce boundaries, shape, and
      motion, through spatiotemporal boundary formation (SBF). The authors report 4
      experiments exploring SBF. The first 3 examine the class of transformations
      producing SBF, indicating that local element changes in color, orientation, or
      location are all effective. A 4th experiment examines temporal constraints on
      SBF. Integration of local element changes to produce boundaries, form, and global
      motion appears to be confined to a 165-ms window. Two classes of spatiotemporal
      integration models are considered; the relation between SBF and other cases of
      boundary interpolation are discussed.

PMID- 8138779
TI  - Effects of truncation on reaction time analysis.
AB  - Many reaction time (RT) researchers truncate their data sets, excluding as
      spurious all RTs falling outside a prespecified range. Such truncation can
      introduce bias because extreme but valid RTs may be excluded. This article
      examines biasing effects of truncation under various assumptions about the
      underlying distributions of valid and spurious RTs. For the mean, median,
      standard deviation, and skewness of RT, truncation bias is larger than some often
      studied experimental effects. Truncation can also seriously distort linear
      relations between RT and an independent variable, additive RT patterns in
      factorial designs, and hazard functions, but it has little effect on statistical
      power. The authors report a promising maximum likelihood procedure for estimating
      properties of an untruncated distribution from a truncated sample and present in
      an appendix a set of procedures to control for truncation biases when testing
      hypotheses.

PMID- 8138780
TI  - Eye movements and the associative basis of contingent color aftereffects: a
      comment on Siegel, Allan, and Eissenberg (1992).
AB  - One of S. Siegel, L. G. Allen, and T. Eissenberg's (1992) recent arguments in
      support of associative-learning explanations of colored aftereffects (CAEs) is
      that the contingencies underlying these effects are not constrained by simple
      stimulus dimensions, such as contour orientation. Specifically, the authors claim
      to have generated CAEs contingent on sets of spatiotopic relationships between
      orientation components of a pattern (as opposed to orientation components per
      se). The present article illustrates how Siegel et al.'s claims are compromised
      by their failure to adequately address the role of fixation and eye movements
      during CAE induction.

PMID- 8138781
TI  - Scanning and form-contingent color aftereffects.
AB  - G. K. Humphrey, A. M. Herbert, L. A. Symons, and S. Kara (1994) and J. Broerse
      and P. Grimbeek (1994) suggested that the form-contingent color aftereffect
      reported by S. Siegel, L. G. Allan, and T. Eissenberg (1992) would not be
      obtained if Ss were instructed to scan the induction and assessment forms. The
      authors present data from Ss who were instructed to scan the forms. These
      scanning Ss displayed aftereffects that were no different from those described
      earlier by Siegel et al. Scanning Ss do display spatiotopic contingent color
      aftereffects.

PMID- 8138782
TI  - Prelexical and postlexical strategies in reading: evidence from a deep and a
      shallow orthography.
AB  - The validity of the orthographic depth hypothesis (ODH) was examined in Hebrew by
      employing pointed (shallow) and unpointed (deep) print. Experiments 1 and 2
      revealed larger frequency effects and larger semantic priming effects in naming
      with unpointed print than with pointed print. In Experiments 3 and 4, subjects
      were presented with Hebrew consonantal strings that were followed by vowel marks
      appearing at stimulus onset asynchronies ranging from 0 ms (simultaneous
      presentation) to 300 ms from the onset of consonant presentation. Subjects were
      inclined to wait for the vowel marks to appear even though the words could be
      named unequivocally using lexical phonology. These results suggested that
      prelexical phonology was the default strategy for readers in shallow
      orthographies, providing strong support for the ODH.

PMID- 8138783
TI  - Dissociations among implicit and explicit memory tasks: the role of stimulus
      similarity.
AB  - This article compares the effect of picture fragmentation level at study on
      performance on a variety of implicit and explicit memory tests. Consistent with
      previous research, a moderately fragmented study picture produced the most
      learning on the implicit memory task of picture fragment completion (Experiment
      1) and speeded picture identification (Experiment 4). In contrast, an intact
      study picture produced the most learning on the implicit memory task of naming
      intact pictures (Experiment 3). These results suggest that performance on 2
      implicit memory tasks can be dissociated by differences in visual similarity
      between the study and test forms of a stimulus. More surprising, parallel effects
      were observed in recognition memory. Recognition memory was best when
      fragmentation levels of the study and test pictures matched (Experiment 2) or
      were comparable (Experiment 1). In contrast to many results in the literature,
      recognition memory was acutely sensitive to surface form differences. We discuss
      the results in terms of 2 types of study-test similarity-stimulus similarity and
      process similarity.

PMID- 8138784
TI  - What makes folk tales unique: content familiarity, causal structure, scripts, or
      superstructures?
AB  - Requiring readers to re-order randomly ordered sentences into a coherent text
      significantly enhances recall relative to that in a read-only control condition
      for non-folk-tale texts but not for folk tales (Einstein, McDaniel, Owen, & Cote,
      1990). Experiments 1-3 showed that embedding components of folk tales (e.g.,
      causal structure, conventional scripts, content related to background knowledge)
      in non-folk-tale texts did not render sentence unscrambling ineffective for
      increasing recall. In Experiments 4a-4c, a folk tale was presented either as a
      fairy tale or as part of a newspaper article. Significant sentence unscrambling
      effects (in free recall) were not obtained in either presentation format, which
      implies that a story superstructure (a story grammar) does not contribute to the
      absence of the sentence unscrambling effect. It is suggested that understanding
      why the sentence unscrambling effect is absent for folk tales may require
      considering the functional role that narrative plays in socioculturally situated
      cognition.

PMID- 8138785
TI  - Dynamics of activation in long-term memory: the retrieval of verbal, pictorial,
      spatial, and color information.
AB  - Paivio's (1986) dual code theory was tested in 5 experiments with a new paradigm
      for the FAN effect that enforced genuine memory recall. Subjects had to learn
      associations between concepts and mediators. The FAN of the concepts in relation
      to the mediators was varied systematically. Response times (RT) were measured
      while subjects had to decide whether 2 concepts were linked to each other or not
      by a common mediator. In Experiment 1 the concepts and mediators were words,
      whereas in the other experiments the concepts were line drawings. Colors served
      as mediators in Experiment 2 and spatial locations served as mediators in
      Experiments 3, 4, and 5. All of the experiments were equivalent with respect to
      the FAN, the learning procedure, and the retrieval test. In all of the
      experiments, RT proved to be a linear function of the FAN. These results
      suggested that the same dynamics hold for all types of information stored in long
      term memory.

PMID- 8138786
TI  - Attention/likelihood theory: reply to Hintzman (1994).
AB  - D. L. Hintzman's (1994) criticism of our theory on recognition memory consists of
      2 points: An equation of attention/likelihood theory has been incorrectly written
      and the likelihood ratios of the theory can be replaced by another, preferable
      transformation. Both of these points are discussed and rebutted.

PMID- 8138787
TI  - Initial recall, reminiscence, and hypermnesia: comment on Madigan and O'Hara
      (1992).
AB  - S. Madigan and R. O'Hara (1992) analyzed data from repeated free-recall
      experiments and concluded that the rate of item recovery across tests was related
      to the level of recall performance on an initial free-recall test. We report a
      reanalysis of these data along with Monte Carlo simulations that indicate the
      measures used by Madigan and O'Hara may have inflated the magnitude of the
      relation between initial recall and item recovery. The results are discussed in
      terms of their implications for future research investigating reminiscence and
      hypermnesia.

PMID- 8138788
TI  - Reducing retroactive interference: an interference analysis.
AB  - In 4 experiments on retroactive interference (RI), we varied paired-associate
      learning lists that produced either appreciable or negligible forgetting. When
      the category of the stimulus word predicted its response word category, and the
      response was relatively unique within its category, learning was extremely rapid,
      and negative transfer and RI were negligible. The more the competing primed items
      in the predicted response category, the slower the learning and the greater the
      RI. If cues and responses were unrelated, learning was very slow, and RI was
      appreciable. Thus, predictive relations that help stimuli retrieve unique
      responses greatly alter forgetting in RI paradigms.

PMID- 8138789
TI  - Incongruous item generation effects: a multiple-cue perspective.
AB  - In a series of studies, generation effects were obtained under encoding
      conditions designed to induce incongruous, unrelated item generation. Experiments
      1 and 2, using free- and cued-recall measures, respectively, provided evidence
      that this unrelated generation effect was due to response-specific processing.
      Experiment 3 demonstrated a lack of relation between free recall and indices of
      clustering. A preliminary protocol study suggested that Ss generate multiple
      items in their search for appropriate unrelated responses. In Experiments 4 and
      5, conditions designed to produce more extensive multiple generations
      demonstrated enhanced free recall. These results supported a multiple-cue account
      of facilitated recall for incongruous item generation. The multiple-cue
      perspective is consistent with traditional conceptualizations of memory, such as
      the principle of congruity, and contemporary distinctions between cue-target
      relational and item-specific processing.

PMID- 8138790
TI  - The information acquired during artificial grammar learning.
AB  - In an artificial grammar learning task, amnesic patients classified test items as
      well as normal subjects did. Item similarity did not affect grammaticality
      judgments when similar and nonsimilar test items were balanced for the frequency
      with which bigrams and trigrams (chunks) that appeared in the training set also
      appeared in the test items. Amnesic patients performed like normal subjects. The
      results suggest that concrete information about letter chunks can influence
      gramaticality judgments and that this information is acquired implicitly. The
      similarity of whole test items to training items does not appear to affect
      grammaticality judgments.

PMID- 8138791
TI  - Lexical and message-level sentence context effects on fixation times in reading.
AB  - Readers' eye movements were recorded as they read an unambiguous noun in a
      sentence context. In Experiment 1, fixation durations on a target noun were
      shorter when it was embedded in context containing a subject noun and a verb that
      were weakly related to the target than when either content word was replaced with
      a more neutral word. These results were not affected by changes in the syntactic
      relations between the content words. In Experiment 2, the semantic relations
      between the message-level representation of the sentence and the target word were
      altered whereas the lexical content was held constant. Fixation time on the
      target word was shorter when the context was semantically related to the target
      word than when it was unrelated. Intralexical priming effects between the subject
      noun and the verb were also observed. The results suggest that both lexical and
      message-level representations can influence the access of an individual lexical
      item in a sentence context.

PMID- 8138792
TI  - Body temperature influence on time perception.
AB  - The chemical clock hypothesis implies a causal link between body temperature and
      the perception of duration. A strict interpretation of this construct requires a
      common slope value in an Arrhenius plot that relates time to temperature for
      every individual tested. Previous studies testing this proposition have confirmed
      a general relationship for data summed across multiple subjects. However, the
      same studies raise doubts as to whether this relationship holds for each and
      every individual tested. Unfortunately, these investigations have been limited by
      methodological constraints, thus, one could argue that the strong isomorphism
      intrinsic to the chemical clock hypothesis has yet to be fairly tested. In the
      present experiment, I sought to distinguish the effects of selective head
      temperature changes on the estimation of duration. Nonlinear decreases in
      estimated duration were observed with ascending deep auditory canal temperature.
      These findings support the contention of a thermally stable region of temporal
      perception bounded by conditions in which temporal estimates directly depend on
      body temperature. In contradicting physiological adequacy as an explanatory
      construct, the present results suggest a direct relationship between time
      perception and the homeothermic platform. I compare these results with earlier
      findings concerning the chemical clock concept and examine respective
      discrepancies as a basis for a fuller understanding of a temporal phenomenon that
      is frequently referred to as the internal clock.

PMID- 8138793
TI  - Loudness adaptation: resolution of a psychophysical enigma.
AB  - Traditional measurement of loudness adaptation based on binaural matching has
      been challenged by Scharf (1983) and others as an artifact of binaural
      interaction due to contrast effects. Weiler, Sandman, and Pederson (1981)
      addressed this problem by developing a monaural technique called the ipsilateral
      comparison paradigm (ICP), which demonstrates strong adaptation effects within
      the auditory system. The two experiments described in this report support the
      meaningfulness of that procedure. They show that the ICP is not confounded by
      psychophysical contrast as suggested by Canevet, Scharf, and Botte (1983); they
      also demonstrate that the results obtained with the ICP are robust--adaptation
      effects were noted across a broad range of intensities and were similar when
      psychophysical reports were made by magnitude estimation and graphic rating
      means.

PMID- 8138794
TI  - Sharing verbal and visuospatial resources in working memory.
AB  - A digit memory task and a delayed visual aiming task were used in a test of
      resource capacity theories. These tasks were run either singly, with short- or
      long-retention intervals, or in pairs. In the dual-task conditions, the short
      version of one was inserted into the longer version of the other. Delay by itself
      had no effect on retention, but the dual-task combinations showed asymmetrical
      interference: Inserting verbal memory into the visual-motor delay had little
      effect on either task, but inserting the motor task into the verbal retention
      interval disrupted both. These results thus support neither single nor multiple
      resource models, but can be explained with reference to component processes in
      working memory.

PMID- 8138795
TI  - Quasi-transfer as a predictor of transfer from simulator to airplane.
AB  - Simulators have emerged as important components of flight-training programs.
      Nevertheless, the development of design principles that can maximize training
      transfer and cost-benefit trade-offs are not well established. The most
      significant challenge to research that would bear on simulator design principles
      is the difficulty and expense of flight transfer experiments. This difficulty and
      expense can be reduced by the use of an insimulator transfer design, designated
      here as a quasi-transfer study, in which transfer is to a high-fidelity
      configuration of a simulator. Of primary concern for such studies is whether the
      implied assumption of correspondence between quasi-transfer and transfer effects
      is well founded. In this article, we review evidence that bears on this issue.
      The evidence is not entirely supportive but does indicate some correspondence
      between quasi-transfer and transfer.

PMID- 8138796
TI  - Sex differences in vigilance performance and perceived workload.
AB  - Female and male subjects monitored the repetitive presentation of a pair of lines
      for occasional changes in height (spatial task) or duration (temporal task).
      Perceptual sensitivity for critical signals favored men in the spatial task,
      whereas no sex differences in signal detectability existed in the temporal task.
      Measurements of perceived workload using the NASA-TLX scale mirrored these
      performance effects. Women tended to rate the overall workload associated with
      the spatial task to be greater in comparison with men. In addition, women found
      the spatial task to be significantly more frustrating, mentally demanding, and
      effortful than men did and rated their own performance lower than their male
      counterparts did. In contrast, no sex-linked differences in perceived workload
      were noted in regard to the temporal task. The results support the suggestion by
      Dittmar, Warm, and Dember (1987) that sex differences in sustained attention are
      task specific.

PMID- 8138797
TI  - Demand transitions and sustained attention.
AB  - A recent report by the National Research Council (Huey & Wickens, 1993) has
      identified transitions in task demand as an important dimension for study in
      vigilance research. This experiment tested the possibility that the effects of
      such transitions follow a relatively simple psychophysical rule--they are
      characterized by contrast effects. Transitions in task demand were achieved by
      shifting subjects from single-task to dual-task monitoring and vice versa. These
      transitions produced changes in subjects' sensing and decision-making functions
      that were far more intricate than simple contrast effects. The demand transition
      issue offers a complex research challenge on both basic and applied levels and
      warrants further investigation.

PMID- 8138798
TI  - The effects of noise and speech on cognitive task performance.
AB  - In the present study, which is based on Loeb's 1986 analysis, we used five levels
      of noise that varied in intermittency and meaningfulness, crossed with sex of
      subject and time of day. Memory tasks that differed in their reliance upon long
      term, short-term free recall, and sequential short-term memory were used as
      dependent variables. A total of 160 subjects, 20 per block, participated in the 2
      x 2 x 5 (Sexes x Time of Day x Noise Conditions) experimental design. Results
      support the prediction that white noise enhances performance on tasks with
      sequential short-term memory demands (anagrams: p < .05; random letter
      generation: p < .002). We found complex interactions by sex of subject, time of
      day, and type of noise for those tasks that placed a heavy demand on short-term
      working memory, i.e., complex sorting (Noise x Sex, p < .05) and random letter
      generation (Sex x Noise x Time of Day, p < .05). The predicted effects for
      anagrams were not supported. These results call into question previous
      generalizations about the effects of noise on performance (Broadbent, 1978;
      Dornic, Sarnelid, Larson, Svensson, & Fernaeus, 1982; Poulton, 1977), alternative
      interpretations are presented.

PMID- 8138799
TI  - Temporal evolution and spatial distribution of the diffusion constant of water in
      rat brain after transient middle cerebral artery occlusion.
AB  - The regional distribution and temporal evolution of the diffusion coefficient
      (Dw) of water in rat brain was measured during and after transient middle
      cerebral artery (MCA) occlusion. Male Wistar rats (n = 14) were subjected to 2 h
      of middle cerebral artery occlusion, induced by intracarotid insertion of a
      filament. Diffusion (n = 14) and perfusion (n = 7) weighted magnetic resonance
      imaging were performed before, and at various time points after MCA occlusion,
      ranging from 30 min up to 7 days. Our data demonstrate that the temporal profiles
      of Dw differ between the severely and the least damaged regions of tissue. In the
      core of the lesion, where the tissue evolved to necrosis, Dw declined
      significantly (P < 0.001) within 0.5 h after onset of ischemia, and remained
      depressed until 24 h after withdrawal of the suture. However, no statistically
      significant decline in Dw was found in the perifocal regions containing
      morphologically intact cells. Perfusion MRI qualitatively exhibited a
      hypoperfusion and reperfusion during, and after 2 h MCA occlusion, respectively.
      A significant (r > or = 0.71, P < 0.01) correlation was found between delta Dw
      (the difference in Dw between the ipsilateral ischemic and homologous
      contralateral control regions) obtained immediately before withdrawal of the
      suture (2 h of ischemia) and at specific early time points after withdrawal of
      the suture, and the degree of ischemic cell damage. No significant (P > 0.01)
      correlation was detected at an early time points of ischemia or at other time
      points after withdrawal of the suture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138800
TI  - Relation between MRI features and dementia in cerebrovascular disease patients
      with leukoaraiosis: a longitudinal study.
AB  - We examined selective MRI features (localization and degree of white matter
      abnormalities, cortical and subcortical atrophy) in relation to cognitive decline
      in patients with cerebrovascular disease (CVD) and leukoaraiosis (LA). We
      enrolled 6 female and 18 male CVD patients (mean age 66.2 +/- 6.6 years) whose
      Magnetic Resonance Images (MRI) revealed LA and who displayed a history of stroke
      or TIA; none showed signs of cortical infarcts or normal pressure hydrocephalus.
      Two blind raters independently scored MRI scans with a high level of agreement.
      All patients underwent extensive clinico-neuropsychological assessment upon
      admission to the study and 19 were followed for an average of 48 +/- 7.6 months.
      Twelve patients were initially classified as non-demented and 12 as demented.
      Three years later, one in the former group had become demented and mental
      impairment had worsened for 6 patients in the latter group; these 7 subjects were
      labeled as "decliners". Ventricular indexes were significantly higher in the
      demented group and correlated with severity of mental impairment, while the
      degree of LA was similar in demented and non-demented subjects. Neither white
      matter lesions nor sulcal and ventricular enlargement differed statistically
      between decliners and non-decliners.

PMID- 8138801
TI  - Bladder sensory power factor (BSPF): a novel diagnostic tool.
AB  - A simple clinical test for assessment of sensory function of the urinary bladder
      is described. It is performed during urodynamic assessment, consisting of
      stepwise filling of the bladder by gas. Subjects give numerical description of
      the perceived magnitude of pressure at each step, using an open-ended ratio
      scale. Based on Stevens law of psychophysics, the bladder sensory power factor
      (BSPF) is extracted from these data, reflecting the sensory state of the bladder.
      A BSPF of 1.01 +/- 0.12 (mean +/- SD) was found for 13 normal subjects. For 20
      patients with lower urinary tract complaints who had a lesion of lumbosacral
      nerve roots, the BSPF was 0.59 +/- 0.23 (P < 0.001, t-test). In 16 (80%) of them
      BSPF was lower than 0.77 (= normal mean -2 SDs), being markedly more sensitive
      than the punctual sensory parameters-bladder sensory threshold (25%) or capacity
      (35%). BSPF is presented as a sensitive and easy to perform test for assessment
      of the sensory function of the human urinary bladder.

PMID- 8138802
TI  - Painless aortic dissection presenting as a progressive myelopathy.
AB  - We report a patient with a painless aortic dissection whose neurologic symptoms
      progressed over 5 days to a complete transverse myelopathy. She did not
      experience pain as her neurologic deficits evolved. Magnetic resonance imaging
      revealed a thoracic aortic dissection extending from the arch to the level of the
      12th thoracic vertebra and demonstrated ischemic changes in the spinal cord and
      one thoracic vertebral body. Aortic dissection must be included in the
      differential diagnosis of spinal cord syndromes even in the absence of pain.
      Early recognition of aortic dissection as a cause of progressive myelopathy may
      become increasingly important as new therapies for central nervous system
      ischemia are developed.

PMID- 8138803
TI  - Different effects of 4-aminopyridine on regenerated cutaneous and muscular rat
      sciatic nerve branches.
AB  - Developing and regenerated myelinated rat dorsal and ventral root fibers respond
      differently to the fast potassium channel blocking agent 4-aminopyridine (4-AP).
      To pursue this issue further, we made unilateral sciatic nerve crushes in adult
      rats. Sural (SN) and lateral gastrocnemius (LGN) nerve branches were collected 4
      6 months later, for physiological and morphological examination. Regenerated and
      control nerves in Ringers solution showed generally similar compound action
      potential (CAP) waveforms, but CAPs of regenerated SNs and LGNs in 4-AP were
      markedly different. While regenerated SNs showed a prominent late CAP negativity
      with a "rippled" appearance and markedly compromised recovery properties, the CAP
      and recovery properties of regenerated LGNs were minimally changed. Light and
      electron microscopic examination of SN and LGN fibers failed to reveal any
      features obviously related to the observed physiological differences. We
      conclude, that the effect of 4-AP on regenerated cutaneous afferents differs from
      its action on regenerated muscular afferents and efferents. This physiological
      diversity lacks obvious structural correlates.

PMID- 8138804
TI  - Axonal regeneration in an articular branch following rat sciatic nerve lesions.
AB  - This study examines the outcome of axonal regeneration in the posterior articular
      nerve of the adult rat knee joint (PAN), after sciatic nerve lesions. Some
      animals had previously been subjected to chemical sympathectomy with
      guanethidine. In crushed cases the number of myelinated PAN axons was 50% above
      control level. The occurrence of C-fibers was doubled, mainly due to an increased
      number of sympathetic efferents. In neurotomy/suture cases the number of
      myelinated fibers was clearly elevated, but the number of C-fibers was close to
      normal. Most C-fibers were sensory. Similar, but less marked, post-regeneration
      abnormalities were seen in the nerve to the lateral gastrocnemius muscle. The
      sural nerve exhibited moderately increased numbers of myelinated and unmyelinated
      fibers in crushed cases. In neurotomy cases, the myelinated axons had increased
      and the C-fibers had decreased in number. The size distribution of myelinated PAN
      axons was less abnormal in crushed cases than after neurotomy, like in the other
      nerves. These results show that the outcome of axon regeneration in an articular
      branch of the lesioned rat sciatic nerve differs from that in non-articular
      branches, and suggest that joints may become hyperinnervated by C-fibers after
      nerve crush lesions.

PMID- 8138805
TI  - Decrease of nerve Na+,K(+)-ATPase activity in the pathogenesis of human diabetic
      neuropathy.
AB  - A decrease in Na+,K(+)-ATPase activity is claimed to play a central role in the
      pathogenesis of electrophysiological and morphological abnormalities that
      characterize the neuropathic complications in different animal models of diabetes
      mellitus. The peripheral nerves from 17 patients with either type I or type II
      diabetes mellitus were studied to assess the importance of changes in Na+,K(+)
      ATPase activity in chronic human diabetic neuropathy. Sixteen nerves from age-
      and sex-matched normal individuals, and 12 nerves from non-diabetic neuropathic
      subjects undergoing vascular or orthopedic surgery served as negative and
      positive controls, respectively. All specimens were processed blind. Ouabain
      sensitive ATPase activity was measured by a modified spectrophotometric coupled
      enzyme assay. Standard histology, fiber teasing and electron microscopy were used
      to establish the normal or neuropathological patterns of surgical material.
      Morphometric analysis permitted calculation of fiber density in each nerve
      specimen and correlation of this figure with the relevant enzymatic activity.
      Na+,K(+)-ATPase activity was approximately 59% lower in nerves from diabetic
      patients than in normal controls (P < 0.01) and approximately 38% lower in nerves
      from non-diabetic patients with neuropathy (P < 0.01). Although nerves from both
      neuropathic conditions had significantly fewer fibers than those from normal
      individuals (diabetic -33%, and non-diabetic -22%), the decreases in Na+,K(+)
      ATPase activity and fiber density were not correlated only in specimens from
      diabetic patients (r2 = 0.096; P = 0.22). Taken together with data from
      experimental animal models, these results suggest that the reduction in Na+,K(+)
      ATPase activity in diabetic nerves is not an epiphenomenon secondary to fiber
      loss; rather, it may be an important factor in the pathogenesis and self
      maintenance of human diabetic neuropathy.

PMID- 8138806
TI  - Antibodies to skeletal muscle in myasthenia gravis. Part 3. Relation with
      clinical course and therapy.
AB  - Fluctuations of anti skeletal muscle antibodies (AMA) were studied in relation to
      clinical changes and fluctuations in anti acetylcholine receptor antibodies (a
      AChR). Forty-two patients with generalized myasthenia gravis were studied in
      clinical and serological follow-up during several years under various conditions.
      Results from this study demonstrate that AMA fluctuate in strong relation to a
      AChR, clinical course and immunosuppressive therapy. Thymomectomy resulted in an
      increase or de novo appearance of AMA in 10 of the 12 patients who did not
      receive immunosuppressive medication.

PMID- 8138807
TI  - Content of mutant mitochondrial DNA and organ dysfunction in a patient with a
      MELAS subgroup of mitochondrial encephalomyopathies.
AB  - A point mutation of mitochondrial tRNALeu(UUR) gene is responsible for a MELAS
      (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes) subgroup of mitochondrial encephalomyopathies. In most cases, the
      mutant mitochondrial DNA (mtDNA) coexists with normal mtDNA in a heteroplasmic
      manner. In order to quantify the content of mutant mtDNA, we developed a
      quantitative method of PCR. Using this method, the distribution of the mutant
      mtDNA was examined in 32 different tissues among 18 autopsied organs from a
      patient with MELAS, who had shown hypophyseal dysfunction. The percentage of the
      mutant mtDNA at nucleotide number 3243 in each tissue was ranged between 22% and
      95%. The content of the mutant mtDNA was at the highest (95%) in the hypophysis
      and higher in the cerebral cortex than in the white matter. This study shows a
      possible correlation of tissue dysfunction with accumulation of the mutant mtDNA
      within the brain.

PMID- 8138808
TI  - Reversal of impaired oxidative phosphorylation and calcium overloading in the in
      vitro cardiac mitochondria of CHF-146 dystrophic hamsters with hereditary
      muscular dystrophy.
AB  - Membrane-mediated excessive intracellular calcium accumulation (EICA), and
      diminished cellular energy charge are invariably present in the myocardium of CHF
      146 strain dystrophic hamsters (DH) with hereditary muscular dystrophy (HMD) and
      hypertrophic cardiomyopathy (HC). Therefore, we investigated respiratory
      dysfunctions and Ca2+ overloading in the isolated cardiac mitochondria from young
      and old DH, and whether these abnormalities can be reversed by controlling EICA
      in the in vitro mitochondria upon chelating excessive Ca2+ from the isolation
      medium with EDTA. Age- and sex-matched CHF-148 strain albino normal hamsters (NH)
      served as the disease controls. As an index of membrane-mediated EICA and chronic
      cellular degeneration, Ca and Mg concentrations were quantitated in the
      ventricular myocardium and in the cardiac mitochondria harvested in two different
      isolation media. Mitochondria from young and old DH, isolated in the absence of
      10 mM EDTA (B0 medium), revealed poor coupling of oxidative phosphorylation,
      diminished stimulated oxygen consumption rate, and lower respiratory control and
      ADP/O ratios, than those seen in NH. However, incorporation of 10 mM EDTA in the
      isolation medium (B medium) restored the mitochondrial functions and reduced
      massive Ca(2+)-overloading in the dystrophic organelles. Ca concentration in the
      in vitro mitochondria from DH was significantly higher than in NH, irrespective
      of the composition of the isolation medium and age of the hamsters. Furthermore,
      the dystrophic organelles isolated in B medium had a much lower Ca concentration,
      and markedly improved oxidative phosphorylation as seen in the cardiac
      mitochondria from NH, compared to those prepared using B0 medium.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138809
TI  - Arachidonic fatty acid in red blood cell membranes, lymphocytes, and cultured
      skin fibroblasts of dominant Charcot-Marie-Tooth syndrome.
AB  - Altered proportions of long-chain unsaturated n - 6 fatty acids (FA) in plasma
      and myelin of the heredodegenerative peripheral neuropathy, Charcot-Marie-Tooth
      syndrome (CMT), may implicate FA metabolism in the pathogenesis of CMT
      demyelination. A significant relationship between low plasma values of the
      polyunsaturated n - 6 FA, arachidonic acid, and an increased amount of
      prostaglandin-mediated immune responses had suggested the possibility of immune
      system metabolic usage of these n - 6 FA rather than an inherited FA enzyme
      defect. This relationship between peripheral immunostimulation and altered FA was
      documented repeatedly in CMT patients. Increased and cyclic lymphocyte activation
      expressions were measured at the same time as low amounts of plasma arachidonic
      acid, which is the FA precursor of prostaglandin immunoregulatory agents. An
      autoimmune process with possible enhanced formation of the n - 6 immune
      prostenoid agents in CMT had also been suggested by increased class II antigen
      expression on CMT sural nerves. Here, normal proportions of total FA in cultured
      CMT skin fibroblasts diminishes a notion of hereditary defects in CMT fatty acid
      metabolism. In addition, a significant depletion of the key arachidonic acid in
      lipid stores of CMT red blood cell membranes with elevated values of this FA in
      functional CMT lymphocytes, compared to controls, support the concept in CMT
      patients of a metabolic diversion of n - 6 FA, particularly arachidonic acid,
      from tissue stores for immunoregulatory prostenoid agent formation.

PMID- 8138810
TI  - Monocyte phenotype in blood and cerebrospinal fluid: compartment-specific pattern
      is unrelated to neurological disease.
AB  - An immunocytochemical study of surface and cytoplasmic markers of the
      monocyte/macrophage lineage was undertaken on peripheral blood (PB) and
      cerebrospinal fluid (CSF) cells in patients with multiple sclerosis (MS) or other
      neurological diseases (OND) and in three healthy controls. Size and granularity
      were assessed by means of cytofluorimetric analysis. Fewer monocytes were
      positive for complement receptors 1 and 3, myeloperoxidase, KiM6, IOM-3 and CD14
      in CSF than in PB. Only DR-positive monocytes were present with the same
      frequency in the two compartments. There was no difference in the monocyte
      phenotype between patients and healthy controls. Furthermore, there was no
      difference between patients with MS or OND. Cytofluorimetric analysis showed that
      in CSF, regardless of clinical status, few cells displayed the physical features
      of blood monocytes. A population of granular and large granular cells that was
      not normally present among PB mononuclear cells was recognized in the CSF. A
      large proportion of these cells was able to adhere to plastic and--when sorted-
      displayed the morphology and surface markers of monocyte lineage. The results of
      our study demonstrate compartment-specific differences in the monocyte phenotype
      between CSF and PB but suggest that these changes may be unrelated to the
      investigated neurological diseases.

PMID- 8138811
TI  - Double mutations at codon 180 and codon 232 of the PRNP gene in an apparently
      sporadic case of Creutzfeldt-Jakob disease.
AB  - Several polymorphisms of the prion protein gene are associated with the
      occurrence of familial Creutzfeldt-Jakob disease. We described a 84-year-old
      Japanese man with neuropathologically verified Creutzfeldt-Jakob disease of
      apparently sporadic type. His clinical presentation was atypical in point of a
      very late age at onset and absence of periodic synchronous discharge on
      electroencephalography. The patient carried double hitherto undescribed mutations
      of the prion protein gene; at codon 180 on one allele and at codon 232 on
      another. The mutation at codon 180 abolishes the Tth111I cutting site, which may
      be misunderstood to represent codon 178 mutation on routine restriction fragment
      length polymorphism study.

PMID- 8138812
TI  - A controlled study of brain magnetic resonance imaging in patients with the
      chronic fatigue syndrome.
AB  - Two neuroradiologists compared the brain MR scans of 52 patients with the CDC
      criteria for the chronic fatigue syndrome (CFS) with those of 52 age and sex
      matched controls who had undergone imaging because of histories of head trauma or
      headache. CFS patients had significantly more abnormal scans than controls--27%
      vs 2%. Abnormalities seen were foci of increased white matter T2 signal in 9 CFS
      patients and one control and ventricular or sulcal enlargement in 5 CFS patients.
      Follow up of patients with subcortical signal hyperintensities revealed 3 who had
      symptoms suggestive of other known medical causes of what appeared to be CFS. The
      data indicate that some CFS patients have some organic problem manifesting itself
      on neuroimaging. But, finding MR abnormalities should warn the physician that the
      patient's symptoms may be secondary to some other medical illness and not simply
      primary CFS.

PMID- 8138813
TI  - The World Federation of Neurology: the formative period 1955-1961. Personal
      recollections.

PMID- 8138814
TI  - Congenital myotonic dystrophy in tropical countries.

PMID- 8138815
TI  - The problem of macular sparing after unilateral occipital lesions.
AB  - Whether or not unilateral occipital damage produces sparing of central vision,
      namely macular sparing, is controversial. We tested two subjects with left
      occipital lesions by means of fundus perimetry combined with fundus image
      analysis. This method made it possible to measure the distance of the stimulus
      projected on the retina from the foveal centre defined as the centre of the
      foveal reflex. The results indicated that macular sparing, if it exists, must be
      less than 0.4 degree wide. Two of the four eyes during the stimulus presentation
      often but not always showed eccentric fixation of a small magnitude, whose mean
      was less than 0.6 degree from the foveal centre in the right hemiretina.

PMID- 8138816
TI  - Active neurocysticercosis, parenchymal and extraparenchymal: a study of 38
      patients.
AB  - In this retrospective study we have analysed a series of 38 patients seen from
      1983 to 1992 (mean follow-up, 4.5 years) with active neurocysticercosis (NCC), 23
      (60.5%) with parenchymal and 15 (39.5%) with extraparenchymal NCC. Classification
      into these two forms of NCC was based on computed tomography and magnetic
      resonance imaging criteria. The enzyme-linked immunosorbent assay performed in
      cerebrospinal fluid, for anti-Taenia solium antibodies, was positive in 18 of 23
      (78%) cases. Epilepsy and/or intracranial hypertension were the most common
      clinical presentation (92%). Twenty-three (60.5%) of 38 patients were treated
      with praziquantel and/or albendazole. In parenchymal NCC, the efficacy of medical
      therapy was complete in 13 of 16 (81%) and partial in 3 of 16 (19%) patients. In
      contrast, in all cases of extraparenchymal NCC treated with cysticidal drugs the
      results were disappointing. A ventriculoperitoneal shunt was performed in 9 of 13
      patients with extraparenchymal NCC and hydrocephalus. Severe complications,
      including two deaths, associated with the natural evolution of the disease or
      with surgery, occurred only in extraparenchymal NCC. Therefore, we confirm the
      existence of the two forms of active NCC, parenchymal and extraparenchymal, which
      are strikingly different in clinical presentation, medical therapy response,
      complications, morbidity and mortality.

PMID- 8138817
TI  - Pontine infarction in acute posterior multifocal placoid pigment epitheliopathy.
AB  - In a patient with acute posterior multifocal placoid pigment epitheliopathy
      (APMPPE), a pontine infarction occurred about 6 months after the ophthalmological
      manifestation. We report the first case with histopathologically proven
      vasculitis shown by muscle biopsy and the first positron emission tomographic
      documentation in APMPPE. The ophthalmological and cerebral symptoms responded
      well to steroid treatment. Long-term immunosuppression (e.g. azathioprine 1-2
      mg/kg) seems to decrease the risk of recurrent systemic vasculitis.

PMID- 8138818
TI  - "Rubral" tremor after thalamic haemorrhage.
AB  - Tremors in association with thalamic haemorrhage have been infrequently reported,
      and delayed rubral tremor as a complication of such an event is quite rare. We
      describe a patient with a combined resting-postural-kinetic tremor due a thalamic
      haemorrhage. Magnetic resonance imaging showed evidence of a subthalamic
      involvement but failed to reveal any mesencephalic lesion. Five years after the
      original stroke there was rapid and almost complete suppression of her abnormal
      movements, probably related to an ischaemic capsular lesion. Involuntary
      movements, which resemble rubral tremor, can be due to lesions upstream of the
      rubral and nigral outflow system.

PMID- 8138819
TI  - Striatal glucose consumption in chorea-free subjects at risk of Huntington's
      disease.
AB  - Controversial data have been reported with regard to the diagnostic value of the
      positron emission tomographic (PET) measurement of striatal glucose consumption
      (rCMRGlc) in chorea-free subjects at risk of Huntington's disease (HD). For
      further clarification of this issue we measured striatal and cerebellar rCMRGlc
      in 27 chorea-free subjects at risk of HD, 20 patients with manifest HD and 20
      control subjects, using PET and 18F-fluorodeoxyglucose. In 6 of the at-risk
      subjects cerebellar ratios of striatal rCMRGlc were decreased below the
      corresponding 99% confidence limit determined in the controls. This indicates
      that the PET measurement of rCMRGlc may, indeed, be valuable in establishing the
      diagnosis of incipient HD in presymptomatic at-risk subjects.

PMID- 8138820
TI  - Blink reflex in patients with an ischaemic lesion of the brain-stem verified by
      MRI.
AB  - The electrically elicited blink reflex was investigated in 25 patients with
      ischaemic lesions of the pons or the medulla oblongata. Only patients with a
      lesion on MRI appropriate to the clinical syndrome were included. Twenty patients
      had an infarction of the pons, bilateral in 5. Additional 5 patients had an
      infarction of the dorsolateral medulla oblongata. Patients with hemispheric
      lesions were excluded. Four of the 5 patients with Wallenberg's syndrome showed
      delayed R2 components to stimulation ipsilateral to the lesion. Additional loss
      of the ipsilateral R1 component was observed in 1 patient. Fifteen of the 20
      patients with pontine infarctions had pathological blink reflexes. All 6 patients
      with a unilateral pons lesion and an abnormality of R1 had this abnormality on
      the side contralateral to the lesion. In 3 cases with bilateral pontine
      infarction R1 was abnormal on one side or on either side. Of 11 patients with a
      normal R1, 6 had isolated abnormalities of R2 without consistent correlation to
      the side of the lesion. We conclude that abnormalities of the blink reflex are of
      minor localizing value in pontine infarction. This may be explained by the fact
      that a pontine infarction affects either the reflex arch itself or descending
      pathways that have a modulating influence on the reflex arch. Infarctions of the
      medulla oblongata, however, have characteristic abnormalities that have already
      been described.

PMID- 8138821
TI  - Beneficial effect of inhaled CO2 in a patient with non-obstructive sleep apnoea.
AB  - A 63-year-old man with severe non-obstructive sleep apnoea (apnoea index 28;
      apnoea duration 45-60s; O2 saturation between 72% and 98%), who did not respond
      to common modes of treatment, was successfully treated with CO2. A tent was
      perfused with compressed air (6 1/min) and increasing amounts of CO2. A
      concentration of 3% CO2 (180 ml/min) was sufficient to raise the PaCO2 above
      apnoea threshold and to suppress apnoeas completely. As a result, O2 saturation
      remained normal throughout the whole night and the symptoms of sleep apnoea
      disappeared. We hypothesize that the PCO2 ventilatory drive was intact in our
      patient and that hypocapnia was the major factor causing the non-obstructive
      sleep apnoea syndrome. Administration of CO2 with a constant flow system could be
      a safe and easy alternative for patients with non-obstructive sleep apnoea
      syndrome who present with hypocapnia and an intact respiratory feedback control
      system.

PMID- 8138822
TI  - Relationship between striatal glucose consumption and copper excretion in
      patients with Wilson's disease treated with D-penicillamine.
AB  - In 12 patients with Wilson's disease treated with D-penicillamine (DPA), the
      regional cerebral metabolic rate of glucose consumption of the lentiform and
      caudate nucleus was analysed using the 18Fluorodeoxyglucose method and correlated
      with the clinical symptoms of the patients, the ceruloplasmin level, the serum
      level of free copper and the 24-h copper excretion. The more copper was
      eliminated, the higher was the basal ganglia glucose consumption. On the other
      hand, in seven patients who had been treated for more than 7 years a significant
      decline of the basal ganglia glucose consumption was observed, suggesting too low
      a maintenance dose of DPA.

PMID- 8138823
TI  - Assessing the impact of essential tremor on upper limb function.
AB  - We compared the impact of essential tremor on the performance of three manual
      tasks: drawing spirals, holding a cup full of water and a joystick-controlled
      tracking test. Tremor amplitude and frequency were measured by accelerometry
      during the tracking test, when holding the cup and whilst a standard posture was
      maintained. The inter-relationships between tremor amplitude, frequency and task
      impairment were then examined. The results showed that the amplitude and
      frequency of essential tremor (measured from the principal spectral peak) changed
      with different activities, with the mildest postural tremors changing most in
      frequency (by up to 4-5 Hz). The amplitude of tremor decreased in almost every
      case during the tasks, relative to posture, and this decrement was greatest for
      the most severe tremors. We also demonstrate that for practical purposes, such as
      routine clinical situations and therapeutic trails, the effect of essential
      tremor upon upper limb function can be usefully assessed by two simple
      complementary techniques: rating spirals and measuring the volume of water split
      from a cup. The impairments in carrying out these tasks and the tracking test
      were highly correlated with one another and also with the amplitude and frequency
      of postural tremor. The concept of tremor "suppressability" is introduced: the
      relative percentage decrease in the amplitude of a particular tremor during the
      performance of a specific task compared to that recorded whilst holding a
      standard posture.

PMID- 8138826
TI  - Magnetic resonance imaging in tonic spasms of multiple sclerosis.
AB  - Two cases of unilateral tonic spasm are described in which high signal lesions
      typical of demyelination were identified on magnetic resonance imaging in the
      contralateral cerebral peduncle. Both cases exhibited subtle upper motoneuron
      signs on the side of the tonic spasms that were exacerbated immediately following
      an attack. In one case, functional impairment of contralateral corticospinal
      pathways was demonstrated by delayed central motor conduction. These cases
      support the view that tonic spasms in multiple sclerosis are due to lesions
      within the corticospinal tract.

PMID- 8138825
TI  - Interleukin-2, soluble interleukin-2-receptor, neopterin, L-tryptophan and beta 2
      microglobulin levels in CSF and serum of patients with relapsing-remitting or
      chronic-progressive multiple sclerosis.
AB  - Cerebrospinal fluid (CSF) and serum levels of interleukin-2 (IL-2), soluble IL-2
      receptors (sIL-2R), neopterin, L-tryptophan (L-TRP) and beta 2-microglobulin
      (beta 2-M) were measured in 31 untreated multiple sclerosis patients in acute
      exacerbation and 27 normal controls. Twenty-six patients showed the relapsing
      remitting type of disease (RRMS); 5 had a chronic-progressive course (CPMS). No
      changes in serum IL-2 and sIL-2R were found between RRMS patients and controls,
      whereas serum and CSF levels as well as the CSF/serum ratio of neopterin were
      significantly elevated in the RRMS group. IL-2 was not detectable in CSF of
      patients or controls and sIL-2R levels were at the level of the lower detection
      (LD) sensitivity of the ELISA method. Four of 23 RRMS patients versus 1 of 25
      controls showed CSF sIL-2R levels above the LD sensitivity, indicating a trend
      towards elevation in acute relapse. No difference was found in serum and CSF L
      TRP and beta 2-M of patients and controls. In CSF of RRMS patients neopterin and
      L-TRP correlated negatively, reflecting the interferon-gamma mediated activation
      of macrophages in acute relapse. A significant positive correlation (Spearman
      rank 0.57, P = 0.001) between serum IL-2 levels and duration of acute relapse
      (mean 30 days) warrants further evaluation.

PMID- 8138824
TI  - Wilson's disease with cerebral manifestation: monitoring therapy by CSF copper
      concentration.
AB  - The clinical courses, cerebrospinal fluid (CSF) and serum copper concentrations
      and urinary copper excretions under different schemes of drug treatment in four
      patients with cerebral manifestations of Wilson's disease were monitored over 6
      11 years. CSF copper concentration measurements were performed from the beginning
      of therapy onwards in three patients and from 16 months after initial treatment
      onwards in the fourth. CSF copper levels decreased slowly over the years in
      parallel with clinical improvements, and increased in one patient who interrupted
      therapy for 2 years. These findings confirm our hypothesis that the concentration
      of copper in the CSF is a valuable quantitative parameter reflecting the
      normalization of copper in the brain. Copper measurements during phases of
      initial neurological deterioration in two patients receiving D-penicillamine, and
      in one patient receiving D-penicillamine and zinc sulphate, revealed decreased
      free serum copper and CSF copper levels.

PMID- 8138827
TI  - Motor evoked potentials following cervical electrical stimulation in brachial
      plexus lesions.
AB  - The diagnostic relevance of recording motor evoked potentials (MEPs) after
      electrical stimulation of the cervical region, as compared with conventional
      needle electromyography (EMG), was evaluated in 26 patients with brachial plexus
      (BP) damage of different aetiology, severity and topography. MEP abnormalities
      (absence or latency increase) were observed in at least one muscle of all the
      patients, with a global incidence of 61.5% of the muscles examined. Neurogenic
      EMG signs were present in all but one patient with an incidence of 62.2% of the
      muscles examined. Combining the two methods, the global incidence of
      abnormalities rose to 69.9%. MEP abnormalities were consistent with the clinical
      topography and severity of BP lesions and were fairly parallel with EMG findings.
      Recording MEPs after percutaneous electrical stimulation of the cervical region
      may be regarded as a rapid, non-invasive method for quantitative
      electrophysiological assessment of BP damage.

PMID- 8138828
TI  - Acute and long-term effects of adrenocorticotropin and dexamethasone on the
      auditory brainstem response in multiple sclerosis patients.
AB  - Auditory brain-stem responses (ABRs) were compared in two groups of multiple
      sclerosis (MS) patients receiving standard treatment with adrenocorticotropin
      (ACTH) and with dexamethasone (DEX). ABRs were recorded prior to treatment, on
      the 1st and 8th day of therapy, and 21 days after the hormonal treatment had been
      discontinued. ABRs in MS patients were within the normal range of variability.
      Latencies of ABR components increased with increasing rate of presentation, and
      with decreasing intensity of the click stimuli. Changes in ABRs displayed a
      consistent pattern in patients treated with ACTH, but showed less coherence after
      DEX. In ACTH treated patients' latencies of the late ABR waves V and Vn were
      prolonged after clicks of high intensity, and reduced following clicks of low
      intensity resulting in a decreased slope of the latency-intensity function of
      these ABR waves. This pattern became most prominent in the recordings after the
      treatment had been discontinued, and could reflect an improved transmission
      across both afferent excitatory and recurrent inhibitory synapses in the auditory
      pathways. The findings indicate that--besides a common anti-inflammatory action-
      therapies with ACTH and DEX differ with regard to their influence on central
      nervous functioning.

PMID- 8138829
TI  - Brain- and muscle-type promoters of the dystrophin gene are selected in
      peripheral lymphocytes and Epstein Barr virus-transformed lymphoblastoid
      [correction of lymphoplastoid] cells.
AB  - Promoter-specific transcripts of the dystrophin gene in peripheral lymphocytes
      and Epstein Barr virus-transformed lymphoblastoid cells were analysed using
      reverse transcription-nested polymerase chain reaction. Two DNA fragments,
      corresponding to the alternative first exons transcribed from either brain- or
      muscle-type promoters, were both amplified from cDNA prepared from normal
      lymphocytes and lymphoblastoid cells. The nucleotide sequences of the amplified
      products were 100% homologous to the 5' termini of the cDNA of brain- and muscle
      type dystrophins, respectively. Neither fragment was amplified from the
      lymphoblastoid cells of a patient with Duchenne muscular dystrophy, who has a
      partial deletion involving the brain- and muscle-type promoters in the dystrophin
      gene. These findings showed that the brain-type as well as the muscle-type
      promoter of the dystrophin gene was active in lymphocytes and lymphoblastoid
      cells.

PMID- 8138830
TI  - Small fibre function in primary autonomic failure.
AB  - A case of primary autonomic failure (AF) with uncomplicated Parkinson's disease
      is presented with clinical and neurophysiological data. Special emphasis is
      placed on new methods of examining impairment of unmyelinated sympathetic and
      afferent C-fibres. Sympathetic vasoconstrictor responses in the skin induced by
      deep inspiration were examined quantitatively with laser Doppler flowmetry. The
      vasoconstriction was markedly depressed in primary AF compared with healthy
      controls and similar to secondary forms of AF. Peripheral nociceptive C-fibre
      function was quantitatively assessed by measurement of axon reflex vasodilatation
      induced by histamine iontophoresis. The axon reflex vasodilatation was completely
      intact in primary AF in contrast to patients with secondary peripheral small
      fibre neuropathy. The results indicate that sympathetic C-fibres are considerably
      affected by the degenerative disease, whereas the afferent C-fibres seem to be
      totally preserved. Modern neurophysiological methods of testing sympathetic and
      afferent small fibre function in combination with other neurophysiological tests,
      e.g. brain-stem auditory evoked potentials, might help to diagnose and
      differentiate primary AF in early stages and make it easier to distinguish
      between secondary autonomic neuropathies of unknown origin that often also
      involve unmyelinated afferent fibres.

PMID- 8138831
TI  - Action myoclonus induced by visually guided movement.
AB  - In order to determine what kind of voluntary movement induces action myoclonus,
      we gave two siblings with sialidosis two kinds of tasks. When the patients were
      asked to move their index fingers following a smoothly moving target, action
      myoclonus became prominent. In contrast, when they were asked to perform the same
      movements with their eyes closed, they could move their index fingers very
      smoothly. This shows that action myoclonus was induced by visually guided
      movement, but not by self-paced movement. Our observations might reflect a
      disorder of the cerebellum, which controls visually guided movement.

PMID- 8138832
TI  - Dietary fat and breast cancer: where do we stand on the evidence?

PMID- 8138833
TI  - Pain and disability associated with new vertebral fractures and other spinal
      conditions.
AB  - Although vertebral fractures are common among older women, little is known about
      associations with pain and disability. In this prospective study, fractures which
      occurred after the initial radiograph were strong predictors of back pain and
      disability at the end of followup, with odds ratios (OR) of approximately 4-5.
      Other, independently significant predictors were self-reported history of (1)
      disk disease (OR = 3-9), (2) traumatic back injury (OR = 4-7), and (3) spinal
      arthritis (OR = 3-6). In longitudinal analyses, new fractures were associated (OR
      = 6.4; 95% CI = 2.6, 15.6) with increases in back pain frequency (relative to pre
      fracture levels). The association with prevalent fractures was weaker, and not
      significant (OR = 1.7; 95% CI = 0.5, 5.6). The pain frequency index increased
      approximately 3-fold, relative to pre-fracture levels. At the end of followup
      (mean = 3.5 years), the index was still two times greater than baseline. We
      conclude that associations with back pain and disability are greater in magnitude
      for new vertebral fractures than for prevalent fractures.

PMID- 8138834
TI  - Prognostic assessment from studies with non-randomized treatment assignment.
AB  - In clinical practice, prognostic factors are primarily used to identify and
      select patients with a relatively poor prognosis who may need more aggressive
      treatment in order to improve their prognosis. Preferably, assessment of the
      ability of prognostic factors to distinguish these high risk patients from low
      risk patients should take place in the absence of such prognosis-modifying
      adjuvant therapy. Adjuvant therapy may dilute the effect of prognosticators
      (covariate-treatment interactions) and such a situation may go unnoticed in tests
      for interaction because of their low statistical power. These undetected
      covariate-treatment interactions will bias the estimated effects of prognostic
      factors in both studies with randomized and non-randomized treatment assignment
      but the bias will usually be greater in studies when treatment was not
      randomized. For the evaluation of prognostic factors, it is therefore argued that
      the study population should be restricted to patients who do not received
      adjuvant therapy. This restriction might result in a less powerful analysis, but
      it carries the advantage that undetectable biases are avoided. Non-random
      treatment assignment will not invalidate this restriction analysis provided that
      all the prognostic factors on which treatment choice was based, are known and
      incorporated into the analysis.

PMID- 8138835
TI  - A comparison of administrative versus clinical data: coronary artery bypass
      surgery as an example. Ischemic Heart Disease Patient Outcomes Research Team.
AB  - Health services researchers rely heavily on administrative data bases, but
      incomplete or incorrect coding may bias risk models based on administrative data.
      The best method for validating administrative data is to collect detailed
      information about the same cases from independent sources, but this approach may
      be too costly or technically difficult. We used data on coronary artery bypass
      surgery from four sites (Duke University; Minneapolis--St Paul; California; and
      Manitoba) to demonstrate an alternative approach for assessing diagnostic coding
      and to explore the implications of miscoding. The first two sites have clinical
      data; the second two have administrative data. The prevalences of 14
      comorbidities and the associated risk ratios for short-term mortality were
      compared across data sets. Some comorbidities could not be precisely mapped to
      ICD-9-CM. Chronic or asymptomatic conditions such as mitral insufficiency,
      cardiomegaly, previous myocardial infarction, tobacco use, and hyperlipidemia
      were far less prevalent in administrative data than in clinical data. The
      prevalence of diabetes, unstable angina, and congestive heart failure were
      similar in administrative and clinical data. Estimates of relative risk derived
      from clinical data equalled or surpassed those derived from administrative data
      for all conditions. Hospitals should be encouraged to improve reporting of
      coexisting conditions on discharge abstracts and claims. In the meantime,
      researchers using administrative data should assess the vulnerability of their
      risk models to bias caused by selective underreporting.

PMID- 8138836
TI  - An illustrative statistical analysis of cutoff-based randomized clinical trials.
AB  - Cutoff-based randomized clinical trials (RCTs) are designed to balance ethical
      and scientific concerns. Patients scoring below a cutoff score on a baseline
      measure (i.e. the least severely ill) are assigned to the control-treated group,
      those scoring above a second cutoff score (i.e. the most severely ill) are
      assigned to the test-treated group, and those scoring within the interval (i.e.
      the moderately ill) are randomly assigned. This paper provides a formal
      illustration on the statistical analysis of cutoff-based RCTs using data from the
      Xanax Cross-National Collaborative Study. To overcome problems specific to cutoff
      based designs, we generally recommend a backward elimination approach that tests
      interactions before main effects.

PMID- 8138837
TI  - Comprehensive evaluation of the Minnesota Leisure Time Physical Activity
      Questionnaire.
AB  - The accuracy of the Minnesota Leisure Time Physical Activity (LTPA) Questionnaire
      (a 1-year survey of non-occupational activity used in MRFIT) was studied in 78
      men and women, age 20-59 years, by comparing survey results to the following
      measures obtained over a year's duration: six 48-hour physical activity records;
      fourteen 48-hour Caltrac accelerometer readings (Caltrac); 14 administrations of
      a 4-week version of the LTPA Questionnaire (FWH); 3 VO2peak determinations and
      percent body fat (% BF). The LTPA Questionnaire demonstrated: weak to moderate
      associations with % BF (r = -0.24) and with VO2peak (r = 0.47); a weak
      association with Caltrac readings expressed as MET.minutes.day-1 (r = 0.23);
      strong associations with corresponding activities reported on the FWH; and
      moderate associations with total and heavy activities reported in the physical
      activity record, but no associations with moderate and light activities.
      Furthermore, several types of LTPA were found to be either under-represented or
      not currently included in the Minnesota LTPA Questionnaire. It is concluded that
      although validation results were found to be quite good, several possible
      refinements were identified, which should improve the accuracy of the Minnesota
      LTPA Questionnaire in assessing habitual physical activity.

PMID- 8138838
TI  - Leisure time physical activity is a significant predictor of body density in men.
AB  - The purposes were to: (a) develop and cross-validate a prediction equation for
      body density with leisure time physical activity (LTA) serving as a potential
      predictor, and (b) determine whether the addition of LTA to previously published
      regression equations would improve their prediction. Body density (hydrostatic
      weighing) was measured in a validation group of 193 men (18-78 years), and was
      predicted by age, body mass index, subscapular skinfold, abdominal skinfold,
      thigh skinfold, waist circumference, and LTA. This equation cross-validated on an
      independent group of men (N = 96). Consequently, groups were combined (N = 289)
      to yield a new equation that also included the same seven variables plus the
      waist/thigh circumference ratio (R = 0.90, R2 = 0.81, SEE = 0.0085 g/ml, p <
      0.0001). Additionally, LTA improved the prediction of published equations
      obtained from men of various ages. In conclusion, LTA is an independent predictor
      of body density in healthy men comprising a wide age range.

PMID- 8138839
TI  - Blood pressure measurement error: its effect on cross-sectional and trend
      analyses.
AB  - The measurement of blood pressure in epidemiological studies is difficult to
      standardize between centres in multi-centre studies and between repeat surveys
      over time. The use of standard mercury sphygmomanometers is common but especially
      prone to measurement error in terms of departure from the protocol and variation
      in measurement technique. Data from Australia's cardiovascular risk factor
      prevalence surveys on 21 independent populations, distributed geographically and
      temporally, has been examined to assess the effect of these errors on cross
      sectional and trend analyses. The examination showed that last digit preference
      for zero may inflate estimates of proportions having high blood pressure. A
      tendency to record identical duplicate measurements could contribute 0.85 mmHg to
      time trends or geographic differences in mean systolic blood pressure (but not
      diastolic blood pressure). Epidemiological studies for geographic and trend
      differentials in systolic blood pressure need to be mindful of these effects in
      their analysis. There was some evidence of deterioration in data quality during
      data collection but no evidence that observers were influenced in their recording
      practice by observable respondents' characteristics. Training procedures for
      blood pressure measurement are of critical importance and adherence to the
      measurement protocol should be continuously monitored during data collection to
      ensure comparability of results.

PMID- 8138840
TI  - Environmental tobacco smoke and heart disease.

PMID- 8138841
TI  - Preliminary reports: when is the evidence strong enough to change practice?

PMID- 8138842
TI  - A study of the association between hormone replacement therapy, smoking and the
      occurrence of myocardial infarction in women.
AB  - The initial results are reported of a case-control study undertaken on the VAMP
      multi-purpose database and designed to estimate the risk for first-time
      occurrence of myocardial infarction in users of hormone replacement therapy
      (HRT). The findings currently available relate to the computerized data and show
      2- to 5-fold increases in risk in smokers and those with diabetes mellitus,
      hypertension or hyperlipidaemia. With any form of HRT, a non-significant
      protective effect [adjusted odds ratio = 0.83 with 95% CI (confidence intervals)
      of 0.66-1.03, p = 0.089] has been shown. However, the protective effect of HRT in
      the data available to date appears to be confined to non-smokers in whom the odds
      ratio in the absence of other risk factors is 0.70 (95% CI of 0.49-1.00). The
      comparable odds ratio in smokers is 1.05 (95% CI of 0.71-1.53). These results
      should be interpreted with caution as smoking status was unknown for about half
      of the subjects and was more complete among the cases than controls.

PMID- 8138843
TI  - Smoking among oral contraceptive users in Quebec in 1987.
AB  - To determine whether an association exists between oral contraceptive (OC) use
      and cigarette smoking, the data base of the 1987 Quebec Health Survey, a cross
      sectional study of a provincial population, was sampled to provide a self
      weighted subsample. This study population consisted of 292 OC users and a
      comparison group of 294 non-users, who would have been eligible to use OCs by
      virtue of their lacking contraindications to their use. 50.5% (95% CI: 44.8%
      56.2%) of OC users smoked, as opposed to 41.0% (95% CI: 35.3%-46.7%) of non
      users. There was a significant association between OC use and smoking; crude OR =
      1.47, 95% CI: 1.06-2.04, p = 0.02. Controlling for effect modifiers and
      confounders by logistic regression revealed that the positive association
      prevails mainly in younger married, separated, and single women, whereas in women
      over 30 and cohabiting women the association is negative. While the negative
      association in women over 30 may reflect the efforts of physicians to prevent the
      adverse interactions between OC use and smoking by preventing older smokers from
      using OCs, the positive association in younger women indicates that physicians
      may be unable to prevent younger OC users from smoking.

PMID- 8138844
TI  - The epidemiological evidence on the carcinogenicity of beryllium in humans.
AB  - Authoritative reviews of the question of whether occupational exposure to
      beryllium compounds is associated with increased risk of respiratory cancer were
      published in 1987 and were critical of the quality of the evidence available up
      to that time. No clear conclusion could be drawn from it as to the
      carcinogenicity of beryllium to humans. If studies published since 1987 are to
      lead to a revision of the regulatory status of beryllium compounds they must
      clearly be of high quality and scientific validity. These studies, as well as the
      earlier reports, are reviewed here. I argue that the small and inconsistent
      excess of lung cancer deaths in employees of one or two plants seen in two post
      1987 studies is compatible with a number of explanations other than that they are
      attributable to occupational exposure to beryllium. Specifically, information on
      cigarette smoking is poor, and the data do not exist to rule out the possibility
      that the small number of excess deaths results from residual confounding by
      cigarette smoking patterns in the populations studied. Indeed, excess deaths from
      emphysema and ischemia heart disease in the same cohort suggest that confounding
      by cigarette smoking is a more likely explanation of the lung cancer excess than
      is occupational exposure to beryllium compounds.

PMID- 8138845
TI  - Proportional mortality analysis of wastewater treatment system workers by
      birthplace with comments on amyotrophic lateral sclerosis.
AB  - There is concern that wastewater treatment system workers are at risk for cancers
      and diseases affecting the neurological and digestive systems. However, these
      diseases have also been linked to early exposures. A proportional mortality study
      was conducted on a large cohort of wastewater treatment system workers who were
      divided into two groups, migrants and nonmigrants, by place of birth as reported
      on their death certificates. The migrant worker group was significantly higher
      than the US white male population for cancer of the stomach, leukemia, and all
      lymphopoietic cancers. Migrant workers also had an elevated ratio for all
      diseases of the nervous system and sense organs. No cases of amyotrophic lateral
      sclerosis were found. The American-born workers had an elevated rate of death for
      arteriosclerotic heart disease compared with the US white male population. We
      suggest that place of birth may present a confounding factor when evaluating
      exposures in employee groups.

PMID- 8138846
TI  - Practices of county medical examiners in classifying deaths as on the job.
AB  - Although annual United States occupational injury fatalities range between 7,000
      and 10,400, consistent rules to determine which deaths are "occupational" do not
      exist. Fifty-seven North Carolina county medical examiners (MEs), responsible for
      more than 50% of all medical examiner cases in 1990, received our questionnaire.
      Fifty-three (93%) responded, classifying 22 scenarios as on-the-job deaths and
      indicating usual classification practices and information sources. Agreement
      varied among the scenarios, but those involving transportation and nonpaid
      workers elicited particularly inconsistent responses. Fifty-six percent of
      medical examiners have a general rule for determining on-the-job status, but
      deaths associated with motor vehicles, farming, and occupations other than the
      decedent's usual job were classified most inconsistently. The lack of standard
      definitions of "job," "work," and "on-the-job" is apparent in classification
      decisions. Certain work situations need special consideration.

PMID- 8138847
TI  - Isokinetic trunk testing and employment.
AB  - Isokinetic trunk testing is often performed to evaluate ability to perform job
      tasks. The purpose of this study was to evaluate the effectiveness of isokinetic
      trunk testing in identifying people with limited functional lifting capability
      and likely future injury potential. Two hundred thirty work applicants for heavy
      labor in a steel mill underwent job-related lifting ability and isokinetic trunk
      evaluation. There was no difference between the isokinetic scores of women who
      did not meet the job lifting criteria and those who did meet the lifting
      criteria. There was no difference between the isokinetic scores of workers who
      experienced occupational low back injury and those workers who did not over
      almost a 6-year follow-up period. In this study isokinetic trunk evaluation was
      of no value in employee selection.

PMID- 8138848
TI  - Respiratory health status in swine producers relates to endotoxin exposure in the
      presence of low dust levels.
AB  - We conducted an assessment of respiratory health status including questionnaire
      and spirographic measurements in 54 male swine producers age 36.3 +/- 11.1 years
      (mean +/- SD) who worked an average of 10.7 +/- 6.3 years in the industry and
      spent 4.7 +/- 2.1 hours per day in the swine barns, and we also measured
      atmospheric contaminants including carbon dioxide, ammonia, total dust,
      respirable dust, and airborne endotoxin. Mean atmospheric dust contaminant levels
      were as follows: carbon dioxide, 2632 +/- 807 ppm; ammonia, 11.3 +/- 4.2 ppm;
      total dust, 2.93 +/- 0.92 mg/m3; respirable dust, 0.13 +/- 0.05 mg/m3; and
      endotoxin, 11,332 +/- 13,492 endotoxin units/m3. Of these, endotoxin related to
      forced vital capacity (P < .05) and endotoxin x hours per day was related to
      forced vital capacity (P < .05) and to forced expiratory volume in 1 second (P =
      .06). Respiratory symptoms and lung function studies did not relate to categories
      of low, medium, and high exposure to respirable dust. However, categories of
      endotoxin (available on 46 workers) related to respiratory symptoms (cough, P =
      .02; chronic bronchitis, P = .06; and to forced vital capacity, P < .01). These
      data suggest that respiratory health status relates to endotoxin levels but not
      to dust level exposures in the presence of low dust levels and indicates that
      control measures should include endotoxin as well as dust control.

PMID- 8138849
TI  - Psychomotor capacity and occurrence of wrist tenosynovitis.
AB  - A case-referent study was carried out among meatcutters, sausage markers, and
      packers in a large meat-processing plant to investigate the association between
      psychomotor capacity and occurrence of tenosynovitis. Reaction time, movement
      time, manual dexterity, visual attention and visuospatial ability were measured
      in 26 cases with a history of two or more episodes of tenosynovitis and 26
      referents of similar gender, occupation, age, and job seniority with no episodes
      of the disease. No differences were found between the cases and the referents in
      any of the tests of psychomotor capacity. The results suggest that psychomotor
      capacity, as measured with the tests of this study, is a poor predictor of wrist
      tenosynovitis.

PMID- 8138850
TI  - Employment as hairdresser and risk of ovarian cancer and non-Hodgkin's lymphomas
      among women.
AB  - The incidence of ovarian cancer and non-Hodgkin's lymphomas (NHL) between 1971
      and 1985 or 1987 has been studied on the basis of cancer registry data among
      women employed in hairdressing or related occupations at 1970 census in Denmark,
      Sweden, Norway, and Finland. Overall, the standardized incidence ratio (SIR) for
      ovarian cancer was 1.18 (95% confidence interval, 0.98 to 1.40). The increase was
      present among hairdressers from Denmark (SIR, 1.23) and Finland (SIR, 1.88);
      whereas hairdressers from Sweden and Norway had an incidence close to expectation
      (SIR 0.95 and 0.96, respectively). In three of the four countries, the SIR was
      higher in 1971 to 1975 than in later years. The SIR for NHL was 1.20 (0.84 to
      1.66); an excess was seen in Denmark (SIR, 1.92) and a decrease was found in
      Sweden (SIR, 0.63). In previous studies, hairdressers have been reported to be at
      increased risk of ovarian cancer: this study adds some evidence in favor of the
      presence of an association. This study also offers some support to the hypothesis
      of an association between exposure to hair dyes and risk of NHL, that was
      reported among personal users from the United States. This study, however,
      strongly suggests that occupational cancer risk among female hairdressers depends
      on temporal and geographical factors.

PMID- 8138851
TI  - Attitudinal, circadian, circumstantial, and subject selection explanations of
      shiftwork effects on health.
AB  - The competing explanations for adverse health symptoms commonly observed in night
      shift workers can be divided into "correlational" and "causational" groups. This
      study monitored health claims and costs over 3 years for all shifts in seven
      industrial plants and administered a survey canvassing a range of behavioral and
      attitudinal dimensions. Shift workers differed from day workers in symptomatology
      and health claims, and, in their feelings of support from management, safety
      attitudes, and practices, felt support from friends and family, alcohol and
      tobacco use, and other dimensions. Because shiftwork was associated with adverse
      health effects but these other measured dimensions were not, the explanation that
      health effects are due to shiftwork itself rather than to its attitudinal or
      demographic correlates is supported.

PMID- 8138852
TI  - Are the job demands on physical work capacity equal for young and aging
      firefighters?
AB  - The job demands on physical work capacity and the frequency of the firefighting
      and rescue tasks were rated by 156 professional firefighters (age range, 22 to 54
      years) who responded to a questionnaire. Smoke-diving requiring the use of
      personal protective equipment was considered to demand most aerobic power. The
      clearing of debris with heavy manual tools, and roof work set the highest demands
      on muscular performance and motor coordination, respectively. During the past 5
      years, 83 to 88% of the respondents had performed these tasks on average four
      times a year. The rating and frequency of the tasks were not significantly
      affected by age. The results suggest that the job demands on physical work
      capacity remain the same throughout the occupational career of the firefighters.

PMID- 8138853
TI  - Progression of chronic obstructive pulmonary disease after multiple episodes of
      an occupational inhalation fever.
AB  - A carding machine operator in a synthetic fabric plant experienced marked
      symptomatic deterioration of obstructive pulmonary disease after multiple
      episodes of an occupational inhalation fever. Polytetrafluoroethylene was used in
      the industrial process and polymer fume fever is suspected as a cause of his
      febrile illnesses. A state industrial hygiene inspection revealed that major
      repairs had been performed on an air scrubber system in close proximity to the
      patient's work area after he had left the plant because of disability. We believe
      that this case provides further evidence that polymer fume fever is not always a
      benign, self-limited illness, especially when workers suffer multiple episodes
      and/or have underlying pulmonary disease.

PMID- 8138854
TI  - Assessment of occupational exposure of pharmaceutical plant workers to 5
      fluorouracil. Determination of alpha-fluoro-beta-alanine in urine.
AB  - The exposure of pharmaceutical plant workers, involved in drug compounding and
      drug production, to 5-fluorouracil (5FU) was studied. 5FU was found by the
      analysis of air and wipe samples. During weighing, 5FU was detected in the air
      (75 micrograms/m3). 5FU was also present on the filter of the mask of the weigher
      (120 micrograms). Before drug compounding 5FU was found on the floor (range, < 1
      to 8 ng/cm2; median, 2 ng/cm2). After routine cleaning significant higher amounts
      of 5FU were measured (range, 70 to 630 ng/cm2; median, 150 micrograms/cm2; P =
      .02). The amounts of 5FU present on several objects were lower when compared to
      the amounts on the floor. The gloves used were always contaminated (range, 22 to
      720 micrograms/pair of gloves; median, 141 micrograms/pair of gloves). The uptake
      of 5FU was established by the determination of alpha-fluoro-beta-alanine, the
      main metabolite of 5FU, in the urine of the workers. Fifty micrograms of alpha
      fluoro-beta-alanine were found in urine of the weigher.

PMID- 8138855
TI  - Subject-based rating of hand-wrist stressors.
AB  - Subject-based rating (SBR) methods (eg, Borg Scales) have been applied to lifting
      and exertion estimation. SBR methods were applied to hand-wrist motions in this
      controlled experimental study of rapid motion. Seven normal volunteers performed
      lift actions with several combinations of wrist position (flexion-extension),
      repetition frequency, force, and grip type (precision vs power) using an
      experimental apparatus. Wrist position and frequency were confirmed using an
      electrogoniometer. Subjects rated the tasks along 5 scales. Analysis showed that
      grip type had the predominant effect on the subjective ratings, but the other
      factors were also rated. However, cycle times between 3 and 8 seconds were not
      well differentiated. The study indicates that SBR does validly reflect actual
      stressors and suggests that SBR may be useful for "screening" jobs for more
      intensive study.

PMID- 8138856
TI  - Effectiveness and cost-effectiveness of employer-issued back belts in areas of
      high risk for back injury.
AB  - Back belts have gained popularity under the assumption that their use will reduce
      low back injuries and thereby decrease the costs. This study sought to examine
      that hypothesis. A retrospective survey instrument was administered to 1316
      workers who perform lifting activities at Tinker Air Force Base, Midwest City,
      Oklahoma, to identify belt use, lifting requirements, injury, and treatment
      history. Analysis was also performed on costs applicable to providing the belts,
      treatment of injury, and lost or limited duty work days. Results show an odds
      ratio of 1.01 (confidence interval 1.01, 1.02) and P value of .0005 of low back
      injury with the number and weight of lifts performed in an 8-hour period as well
      as an odds ratio of 5.56 (confidence interval 3.35, 9.26) with prior history of
      injury. A protective effect, odds ratio of .65, P value of .019 is noted between
      lifting and attendance at a back training program. Use of a back belt appears to
      be marginally effective (odds ratio .60, P value .0508) in reducing injuries when
      controlling for other related factors. Cost analysis over all diagnoses of low
      back injury shows less intensive treatment and lower cost per injury for workers
      injured without a belt versus those injured while wearing a belt. It appears that
      predictors of low back injury are those expected based on risk assumed (amount of
      time spent performing lifts, history of injury) and that training programs are
      effective in prevention of problems. Data suggest that back belts appear to be
      minimally effective in preventing injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138857
TI  - Ethical dilemmas in intravenous nursing: a problem-solving model.
AB  - There is no single task that nurses do more often than make decisions, yet many
      clinicians feel inadequately prepared to address and resolve ethical issues. The
      Intravenous Nurses Society Code of Ethics provides practice guidelines for
      intravenous nursing specialists who need to make these often difficult decisions.
      The availability of an ethical decision-making model can assist the IV nurse in
      providing ethical quality care, regardless of the clinical setting in which care
      is delivered.

PMID- 8138858
TI  - The value of certification in a patient-driven healthcare system.

PMID- 8138859
TI  - The use of humor in intravenous nursing.
AB  - Providing a daily dose of laughter is often the best medicine we can offer our
      patients, their caregivers and, most importantly, ourselves. Humor creates an
      environment of healing, which is essential when treating a patient on a daily
      basis. In this article, the author describes the many uses of humor in
      intravenous nursing practice and offers suggestions about how humor and laughter
      can be incorporated into patient care routines.

PMID- 8138860
TI  - Project management for nurses: guidelines for success.
AB  - Nurses often are called on to plan, participate in, and manage special projects.
      These projects and special assignments can be managed most effectively when
      business principles of project management are applied. This method includes
      defining the project, developing a work breakdown structure, assigning resources,
      calculating budget implications, presenting and negotiating the plan,
      implementation, and evaluation. When appropriately used, project management
      skills can have a major impact on the success or failure of a plan.

PMID- 8138861
TI  - Latex allergy: implications for healthcare personnel and infusion therapy
      patients.
AB  - The health care arena has been dramatically impacted by the implementation of
      universal precautions and OSHA standards, mandating the use of disposable gloves.
      These directives promote the judicious use of gloves as a barrier against contact
      with blood and body fluids. An increasing number of hypersensitivity reactions to
      latex are being reported by the medical community. The FDA cites that 6%-7% of
      surgical personnel are latex sensitive as well as 18%-40% of spina bifida
      patients. Sensitivity reactions range from mild delayed symptomatology in the
      form of eczematous contact dermatitis, to severe systemic reactions including
      death. Besides gloves, latex is found in catheters, i.v. tubing, injection caps
      and anesthesia masks. Latex sensitivity creates yet another infusion therapy
      challenge for the i.v. clinician.

PMID- 8138862
TI  - Teaching intravenous therapy using innovative strategies.
AB  - The role of teacher is inherit to the profession of nursing. Whether teaching
      occurs in the formal classroom setting, education departments, or at the bedside,
      the audience is usually the adult learner. The six strategies (including ice
      breakers, feedback lecture, concept mapping, and games) and the media tips
      presented in this article provide an alternative to the traditional classroom
      setting by using adult learning principles as a basis for teaching intravenous
      therapy. Teaching i.v. therapy requires appropriate use of audio and visual
      educational media and coordination with the audience and the subject content of
      the presentation.

PMID- 8138863
TI  - Interventions in pediatric psychology: a look toward the future.

PMID- 8138864
TI  - Helping preschool leukemia patients and their parents cope during injections.
AB  - Taught 4 preschool leukemia patients (ages 3-5) to engage in specific coping
      behaviors before and during painful intramuscular and intravenous injections.
      Parents were taught to coach their children in the use of the coping behaviors.
      Intervention was delivered in a multiple baseline across-subjects design. Parent
      and child behavior was coded using the Child-Adult Medical Procedure Interaction
      Scale-Revised (CAMPIS-R, Blount, Powers, & Sturges) and Observation Scale of
      Behavioral Distress (OSBD, Elliott, Jay, Woody). Parents and nurses rated child
      behavior as well. Results indicated that parents learned coping-promoting
      behaviors, children learned specific coping behaviors, and children displayed
      less behavioral distress. Maintenance of behavior change was addressed.
      Contributions of this study to the current literature on children's coping with
      invasive medical procedures and implications for future research and clinical
      practice are discussed.

PMID- 8138865
TI  - Effects of behavioral psychophysiological treatment on schoolchildren with
      migraine in a nonclinical setting: predictors and process variables.
AB  - Evaluated the outcome of a combined behavioral therapy, comprising relaxation
      training, temperature biofeedback, and cognitive training, administered in a
      school setting, at posttreatment, and 7-month follow-up, on a group of
      schoolchildren with migraine. Comparison between the experimental group (n = 32)
      and the waiting-list control group (n = 9) showed a treatment effect on headache
      frequency and duration but not on intensity. Using a 50% reduction in the
      headache activity as a criterion for clinical improvement, 45% of the children in
      the experimental group were clinically improved at the end of the treatment. The
      treated subjects were found to have maintained significant improvement at follow
      up. Sex, headache history, age, and psychosomatic complaints before the training
      emerged as predictors of outcome. A decrease in state anxiety and an increase in
      the ability to relax during the sessions contributed to headache improvement.
      Finally, the acquired capacity to raise one's finger temperature during the
      biofeedback sessions was related to headache reduction after the training.

PMID- 8138866
TI  - Methods of evaluating methylphenidate in children with attention deficit
      hyperactivity disorder: acceptability, satisfaction, and compliance.
AB  - Compared two methods of evaluating methylphenidate (MPH) on measures of parental
      acceptance, satisfaction, and compliance with the treatment. Twenty-four 6- to 10
      year-old children with Attention Deficit Hyperactivity Disorder (ADHD) were
      randomly assigned to either a blind, placebo-controlled medication trial (MT) or
      to a typical clinical procedures (TCP) evaluation that was nonblind and without a
      placebo control. Ratings of satisfaction were significantly higher in the MT
      condition than in the TCP condition; however, all parents became more accepting
      of MPH after participating in an evaluation. Both during the evaluation and at 6
      week and 3-month follow-ups, approximately 20% of cases were not complying with
      treatment. However, rates of compliance did not differ between the MT and TCP
      conditions.

PMID- 8138867
TI  - Treatment of childhood sleep disorders: generalization across disorders and
      effects on family members.
AB  - Investigated the treatment of bedtime problems and its generalization to night
      wakings. Six children (M age = 35 months) and their parents participated in this
      study. A multiple-baseline design across subjects was employed and found that
      treatment instituted at bedtime was successful in relieving both bedtime
      disturbances and night wakings. Furthermore, significant positive changes in
      parental sleep and family satisfaction occurred following amelioration of the
      children's sleep problems. Data support recent work suggesting that chronic sleep
      problems in children are amenable to behavioral interventions. In addition, this
      method appears to be more cost-effective and less stressful for parents to
      implement than behavioral interventions that directly target night wakings.

PMID- 8138868
TI  - The impact of social skills training on the adjustment of children with newly
      diagnosed cancer.
AB  - Randomized 64 children ages 5 to 13 years with newly diagnosed cancer to either a
      Social Skills Training experimental treatment group or a School Reintegration
      standard treatment group. Children who received explicit training in social
      skills reported higher perceived classmate and teacher social support at the 9
      month follow-up in comparison to pretreatment levels, while parents reported a
      decrease in internalizing and externalizing behavior problems and an increase in
      school competence. Methodological improvements for Phase III clinical trials are
      addressed.

PMID- 8138869
TI  - Drug refusal behavior: the relative efficacy of skills-based and information
      based treatment.
AB  - Examined the impact of two treatment strategies on children's drug refusal skills
      and drug-related information. Fifty-seven third graders were randomly assigned to
      one of three groups: rehearsal-plus, general information, and control. Children
      in the rehearsal-plus group were taught drug knowledge, assertiveness skills,
      decision-making skills, rationale and specific drug refusal skills in the context
      of a skills-based strategy. At a more global level, the general information group
      targeted all of the same components with the exception of rationale. Results
      indicated that children in the skills-based strategy (rehearsal-plus) showed
      significant improvement in behavioral skills, decision-making, and rationale,
      while children in the information/education-based strategy (general information)
      improved most on the measure of general knowledge. At follow-up, gains were
      generally maintained.

PMID- 8138870
TI  - Preparation and study of release kinetics of rosin pentaerythritol ester
      microcapsules.
AB  - Rosin was esterified with pentaerythritol and intermediate reaction products with
      different acid values were isolated. Microcapsules containing sulphadiazine were
      prepared by a solvent evaporation technique using these esters as wall materials.
      The microcapsules were evaluated for their size, drug content, and release
      characteristics in simulated gastric and intestinal fluids. The microcapsule size
      increased as the acid value of the ester decreased. The release of the drug was
      studied by using first-order, Higuchi and Hixon-Crowell cube root models. The
      release mechanism of the microcapsules is discussed.

PMID- 8138871
TI  - Preparation and in vitro characterization of a magnetically responsive ibuprofen
      loaded erythrocytes carrier.
AB  - The erythrocytes were loaded with ibuprofen and magnetite (ferrofluids) using the
      pre-swell technique. Various process variables including drug concentration,
      magnetite concentration, sonication of ferrofluids that could affect the loading
      of drug and magnetite were optimized. The loaded erythrocytes were characterized
      for in vitro drug efflux, haemoglobin release, morphology, osmotic fragility,
      turbulence shock, in vitro magnetic responsiveness and percentage cell recovery.
      In optimum concentration erythrocytes could tolerate ibuprofen as no appreciable
      detrimental effects were noticed on cell morphology, osmotic fragility, and
      turbulence shock, when compared with normal erythrocytes. However, magnetite
      showed some detrimental effect on erythrocytes. A drug release profile from the
      cellular system was observed to follow approximate zero-order kinetics. The
      loaded cells effectively responded for an external magnetic field of 8.0 KOe.

PMID- 8138872
TI  - Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion.
      II. Drug removal and polymer compatibility studies.
AB  - The newly developed system of polyacrylate-polymethacrylate-coated charcoal,
      filled in a column has been tested for its efficiency in removing theophylline,
      as a model drug both from a buffer solution pH 7.4 and human plasma using a
      closed-circuit apparatus. Preliminary testing determined the capacity of the
      charcoal column and the effect of circulation rate of the buffer solution on the
      clearance of theophylline. It was found that the circulation rate does not
      significantly affect the clearance rate of theophylline, while the concentration
      of drug in the buffer solution has a considerable effect on the clearance of the
      drug, presumably due to the saturation of the column. The clearance of the drug
      from plasma in comparison to buffer solution was also investigated. It was found
      that more than 70 per cent of the drug was removed from the buffer solution
      within the first 15 min as compared with 65 per cent from plasma; with 95 per
      cent removed from buffer after 1 h in comparison to 93 per cent from plasma. The
      blood compatibility of the polymer was studied by incubating various
      concentrations (5-25 per cent w/v) of the polymer in blood for 30 min at 25
      degrees C. A concentration of 5 per cent polymer was also incubated for a series
      of incubation times. The results indicated that with polymer concentrations up to
      15 per cent there is no significant lysis of RBCs in comparison to a
      blank.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138873
TI  - Microencapsulation within crosslinked polyethyleneimine membranes.
AB  - A microencapsulation technique is proposed involving the formation of a
      polyethyleneimine (PEI) membrane crosslinked by an acid dichloride. The membranes
      were formed at pH 8 in a non-polar solvent, conditions which are better suited
      for the encapsulation of biocatalysts or fragile biochemicals than those using
      polyamide membranes. The mean diameter and size distribution of the PEI
      microcapsules were similar to that observed with nylon membranes. The resultant
      microcapsules were spherical, free-flowing with a strong membrane. The mass of
      membrane was seen to be independent of the reaction time (1-4 min), insensitive
      to the PEI concentration and proportional to the concentration of crosslinking
      agent.

PMID- 8138874
TI  - Preparation and characterization of liposomes containing a lipophilic cisplatin
      derivative for clinical use.
AB  - Cis-bis-neodecanoato-trans-R,R-1,2 diaminocyclohexane platinum(II) (NDDP) is a
      lipophilic cisplatin derivative that has been formulated entrapped in
      multilamellar liposomes composed of dimyristoylphosphatidyl choline (DMPC) and
      dimyristoylphosphatidyl glycerol (DMPG). A phase I clinical study with liposome
      entrapped NDDP (L-NDDP) administered i.v. every 4 weeks has been recently
      completed. L-NDDP was synthesized, manufactured, and reconstituted for clinical
      use in our laboratories. L-NDDP was prepared as a lyophilized powder containing
      the NDDP and the phospholipids (NDDP-lipid weight ratio 1:15; DMPC-DMPG molar
      ratio 7:3). The liposome suspension was obtained on the day of use just before
      administration to the patients by adding normal saline (final concentration 1 mg
      NDDP/ml) and shaking in a water-bath shaker at room temperature according to an
      established protocol. A total of 54 batches of lyophilized L-NDDP were prepared.
      Physical appearance, phospholipid content and integrity, and elemental platinum
      content were determined in all batches and found to be reproducible. All batches
      contained < 0.24 ng/ml endotoxin. The amount of residual organic solvents was <
      0.05 per cent. In all reconstituted doses, drug entrapment was > 90 per cent, and
      the proportion of liposomes measuring > 5 microns was < 20 per cent. Our results
      show that reproducible batches of liposomal preparations of new compounds can be
      prepared in the laboratory facilities of academic institutions, thus allowing for
      early clinical trials with novel therapeutic agents.

PMID- 8138875
TI  - Microencapsulation studies on aminophylline involving spherical crystallization,
      spheronization and drug loading on to non-pareil seeds.
AB  - Aminophylline was formulated as small spherical cores for subsequent coating in
      an attempt to develop a competitor microencapsulated product to the commercial
      available sustained-release tablet, Phyllocontin. Optimum spherical
      crystallization conditions yielded cores of loosely adhering crystals of active,
      with highly irregular surface morphology and poor mechanical strength during pan
      coating. Aqueous spheronization yielded satisfactory cores in high yield when
      microcrystalline cellulose and liquid paraffin were used. However, application of
      large amounts of controlled-release coatings based on Eudragit RL and RS failed
      to produce a product with retarded drug dissolution comparable to the commercial
      product. Drug loaded non-pareils were easily formed, but required application of
      about 20 per cent Eudragit RL/RS coating to achieve adequate prolonged-release
      properties. Application of 10 per cent hydrogenated castor oil/ethylcellulose
      based coating gave acceptable in vitro release only if the microcapsules formed
      were tableted and annealed. All products investigated rapidly discoloured during
      storage and none were considered to represent a realistic alternative to
      tableting technology for the production of a sustained-release oral dosage form
      of aminophylline.

PMID- 8138876
TI  - Controlled release of anticancer drug methotrexate from biodegradable gelatin
      microspheres.
AB  - Biodegradable hydrophilic gelatin microspheres containing the anticancer drug
      methotrexate (MTX) of different mean particle sizes (1-5, 5-10, and 15-20
      microns) were prepared by polymer dispersion technique and crosslinked with
      glutaraldehyde. The microspheres were uniform, smooth, solid and in the form of
      free-flowing powder. About 80 per cent of MTX was incorporated in gelatin
      microspheres of different sizes. The in vitro release of MTX was investigated in
      two different media, namely simulated gastric and intestinal fluids. The release
      profiles indicated that gelatin microspheres released MTX in a zero-order fashion
      for 4-6 days in simulated gastric fluid and for 5-8 days in simulated intestinal
      fluid. The rate of release of MTX decreased with increase in the particle size of
      the microspheres. MTX release was faster in gastric fluid when compared to
      intestinal fluid.

PMID- 8138877
TI  - Characterization of diazepam submicron emulsion interface: role of oleic acid.
AB  - Oleic acid markedly improved the physical stability of a diazepam submicron
      emulsion. The zeta potential of the emulsion increased with increased oleic acid
      concentration. This effect suggested that adjustment of the diazepam submicron
      emulsion pH to 7.8-8.0 led to the ionization of oleic acid molecules at the
      oil/water (o/w) interface without being excluded from the surface regions of the
      oil droplets. TEM freeze-fracturing examination revealed that a mixed-emulsifier
      monolayer film was established at the o/w interface of the submicron emulsion. No
      liquid crystal or liposome formation was detected. This was confirmed by the
      results of phosphatidylethanolamine surface labelling at the o/w interface of the
      emulsion. The improved stability properties conferred to the emulsion by oleic
      acid should be attributed not only to the zeta potential increase, but also to
      the strengthening of the molecular interactions occurring between phospholipid
      and poloxamer emulsifiers in the presence of an ionized form of oleic acid at the
      o/w interface of the emulsified oily droplets as evidenced in independent
      monolayer studies.

PMID- 8138878
TI  - A measurement model for the Type A Self-Rating Inventory.
AB  - Compared to other questionnaire measures of Type A behavior, the Type A Self
      Rating Inventory (TASRI) possesses particularly strong face validity. This study
      sought to develop a formal measurement model for the TASRI using a sample of 352
      male and 479 female undergraduate psychology students. Assessed via structural
      equation modeling, an oblique two-factor (Hard-Driving, Extroverted) model
      explained over 90% of the common variance in responses to a subset of 13 of the
      original 28 TASRI items for men, women, and the pooled data. As hypothesized,
      relative to women, men had a greater mean score on the Hard-Driving factor and a
      lower mean score on the Extroverted factor. However, the magnitude of these
      gender differences is small. When reconceptualized in the context of work on the
      Big Five factor model, the Hard-Driving and Extroverted factors were found to
      reflect related elements of positive sociability and negative power,
      respectively.

PMID- 8138879
TI  - Development of a California Q-set indicator of primary psychopathy.
AB  - Seven judges described the personality characteristics of the primary psychopath
      by sorting the 100 items of the California Q-set in a forced-normal distribution.
      Item scores resulting from these sorts were aggregated across judges to form a
      Psychopathy Prototype. The reliability of the seven-judge aggregate prototype was
      .90. To examine the reliability of scores derived from the prototype, the
      personalities of 65 target subjects were described by two peer judges using the
      California Q-set (Block, 1961). For each subject, Psychopathy Prototype scores
      were derived by correlating each judge's Q-sort profile with the Psychopathy
      Prototype. Findings indicated that the peer-generated psychopathy scores
      correlated r = .61 between judges. Using the Spearman-Brown formula, Psychopathy
      Prototype scores have reliabilities of .75, .82, and .86 when aggregated over
      two, three, and four peer judges, respectively. To further explore properties of
      the measure, the Psychopathy Prototype was compared with independently developed
      California Q-set prototypes describing the narcissist and the female hysteric.
      The results revealed some interesting contrasts among these concepts and serve to
      support our contention that the Psychopathy Prototype has utility in regard to
      distinguishing between pathologies with overlapping features.

PMID- 8138880
TI  - The development of the MMPI-A Immaturity Scale: findings for normal and clinical
      samples.
AB  - The Immaturity (IMM) Scale was developed as a supplementary scale for the
      Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A). This study
      describes the development of the IMM Scale and presents some concurrent validity
      data derived from the MMPI-A normative sample of 1,620 adolescents and a clinical
      sample of 122 adolescent inpatients. The IMM Scale was examined in relation to
      Biographical and Life Events data to identify external correlates for the MMPI-A
      normative sample. In the clinical sample, external correlates were derived from
      diagnostic and rating form data provided by the adolescents' treatment staff and
      by their parents. Current findings were discussed in terms of the relationship of
      correlate patterns to descriptions of the preconformist and conformist stages of
      Loevinger's (1976) concept of ego development, and future research directions
      were suggested.

PMID- 8138881
TI  - On McClanahan and Holmbeck's construct validity study of the Separation
      Individuation Test of Adolescence.

PMID- 8138882
TI  - Construct and content validity of the Separation-Individuation Test of
      Adolescence: a reply to Levine.
AB  - The purpose of this commentary is to respond to Levine's (1994) critique of our
      earlier article (McClanahan & Holmbeck, 1992). We agree with Levine's argument
      that changes in the subscales of the Separation-Individuation Test of Adolescence
      (SITA; Levine, Green, & Millon, 1986) should be made based on both theoretical
      and statistical considerations. On the other hand, we also argue that attention
      needs to be paid to the content and construct validity of the SITA in future
      revisions of the measure.

PMID- 8138883
TI  - The MMPI and MMPI-2 as predictors of psychiatric diagnosis in an outpatient
      sample.
AB  - The MMPI and MMPI-2 were compared as predictors of psychiatric diagnosis in 100
      male and 100 female outpatients who completed the test items in a single session.
      Test profiles and the clinical diagnosis were grouped into five categories
      (normal, neurotic, character disordered, psychotic, and other). The MMPI and MMPI
      2 code types were in the same category in 75% of the cases. Both the MMPI and
      MMPI-2 had a 39% agreement rate with category of clinical diagnosis (p < .0001).
      Discriminant function analyses based on Scales L, F, K, 1, 2, 3, 4, 6, 7, 8, and
      9 accounted for significant variance in diagnostic group, (p < .02), and two
      functions correctly classified 49% and 50% of the cases for the MMPI and MMPI-2,
      respectively. The rate of correct classification for normals was more than 70%.
      The rate of correct classification for psychotics was 55% for the MMPI and 30%
      for the MMPI-2. For both the MMPI and MMPI-2, it appears important not to rely on
      test findings alone as a basis for diagnostic decisions.

PMID- 8138884
TI  - Weiner's Psychodiagnosis in schizophrenia: a classic revisited.

PMID- 8138885
TI  - Psychological assessment of airline pilot applicants with the MMPI-2.
AB  - Psychological tests like the Minnesota Multiphasic Personality Inventory (MMPI)
      have been used widely to assess personality characteristics and appraise
      potential mental health problems of individuals applying for responsible
      positions. This study had three major goals: First, these data allowed for an
      evaluation of the effects of the new norms for the traditional validity and
      clinical scale scores of the MMPI-2 in an employment selection program. Second,
      the effects that test defensiveness had on the MMPI-2 scores of a group of
      individuals, airline pilot applicants who were taking the test in a preemployment
      context, were evaluated. Third, useful descriptive information was provided on
      the performance of airline pilot applicants on MMPI-2 scales to give interpretive
      guidelines for using the MMPI-2 in psychological screening. A sample of 437
      airline pilot applicants seeking employment as airline flight crew members was
      administered the MMPI-2. Results of the study showed that the MMPI-2 norms were
      more appropriate for characterizing pilot applicants than were the original MMPI
      norms, which tended to overpathologize test takers. The effects of defensiveness
      on MMPI-2 profiles were found to be pronounced. Interpretive guidelines for using
      the MMPI-2 in personnel screening were proposed.

PMID- 8138886
TI  - An empirical study of malingering schizophrenia on the Rorschach.
AB  - We investigated whether it is possible to fake schizophrenia on the Rorschach
      test. We also developed and attempted to validate variables (modified responses)
      that might distinguish malingerers from true schizophrenics. Forty
      nonschizophrenic, nonpatient subjects, randomly assigned to either a control or
      malingering condition, and 20 schizophrenic subjects were administered the
      Rorschach. Dependent variables included indices associated with schizophrenia and
      modified responses. As expected, some malingering subjects did successfully fake
      schizophrenia. Modified responses did help to distinguish groups but were not
      completely successful. Post hoc analyses of differences were also presented. We
      concluded (a) that some malingerers, given some information about schizophrenia,
      may successfully fake schizophrenia and (b) that the modified responses show
      promise in assisting detection of malingering.

PMID- 8138887
TI  - A Rorschach investigation of sexual homicide.
AB  - A sample of incarcerated sexual homicide perpetrators (n = 18) were compared to a
      sample of non-sexually offending but violent male psychopaths (n = 23) on select
      Rorschach variables using the Comprehensive System (Exner, 1991). Results suggest
      that sexual homicide perpetrators are similar to psychopaths in their attachment
      abnormality, characterological anger, pathological narcissism, moderate and
      pervasive formal thought disorder, and borderline reality testing. They are
      distinguished, however, by a more frequent affectional hunger, a tendency to
      engage in more dysphoric rumination, and abnormal elevations of nonvolitional
      ideation (obsessional thoughts) due to unmet instinctual need states. They also
      show a greater interest in others as whole, real, and meaningful objects. Five
      psychodynamic factors, supported by the empirical findings, are proposed to
      partially explain the intrapsychic mechanisms involved in an act of sexual
      homicide.

PMID- 8138889
TI  - Personality correlates of the Hypercompetitive Attitude Scale: validity tests of
      Horney's theory of neurosis.
AB  - This study focused on assessing the concurrent validity of Horney's ideas about
      the personalities of hypercompetitive individuals based on her theory of
      neurosis. One hundred and sixty university men and women provided data by
      responding to a test battery of personality inventories containing measures of
      hypercompetitive attitudes and several theoretically relevant constructs. The
      results strongly support Horney's contentions. Stepwise multiple regression
      analysis indicated that hypercompetitive individuals were high in narcissism,
      Type E orientation, and several aspects of sensation seeking. The discussion
      centered on hypercompetitiveness as a mental health problem in American society
      and on the scale's utility in the diagnosis of the problem and in the assessment
      of therapeutic change in clients.

PMID- 8138888
TI  - Confounding factors in the measurement of depression in HIV.
AB  - Our study investigates the nature of elevated depression scores on the MMPI-168
      in human-immunodeficiency-virus- (HIV-)infected individuals. Comparison of MMPI
      scales, factor scores, and individual depression item endorsement rates were made
      between three groups of homosexual/bisexual men: asymptomatic HIV-1 seropositives
      (n = 156), symptomatic HIV-1 seropositives (n = 156), and a comparison group of
      HIV-1 seronegatives (n = 117). Elevated scores were found on the MMPI depression
      scale for all three groups, with HIV infection and the presence of symptoms being
      associated with significant elevations in depression. Analyses of these elevated
      scores through the use of factor scores and individual item analyses strongly
      suggest that endorsement of items related to physical symptoms and
      neuropsychological complaints accounted for much of the difference in overall
      depression scores between samples. Implications are discussed for measurement and
      diagnosis of depression in HIV populations.

PMID- 8138890
TI  - Perceptions of MMPI item subtlety: influences of age and ethnicity.
AB  - This study examined the influences of age and ethnicity on perceived item
      subtlety in Minnesota Multiphasic Personality Inventory (MMPI) Scales F and 9.
      One hundred twenty-one male adolescents (67 White, 54 Black) rated the items
      composing these scales in terms of their relationship to a psychological problem.
      The mean item ratings and subsequent subtle-obvious classifications were then
      compared to established ratings obtained from adults (Christian, Burkhart, &
      Gynther, 1978; Wiener, 1948). Results indicated significant differences in both
      item ratings and classifications between adolescents and adults on Scales F and
      9. Significant differences between Black and White adolescents were found on
      Scale F but not on Scale 9, even when differences in verbal-comprehension
      abilities between groups were considered. These results suggest that it may be
      inappropriate to use current subtle-obvious keys with adolescents and minorities.

PMID- 8138891
TI  - Saturable elimination and saturable protein binding account for flavone acetic
      acid pharmacokinetics.
AB  - Flavone acetic acid (FAA) is an antineoplastic agent that has undergone extensive
      study in Phase I trials. Concentration-dependent plasma protein binding has been
      demonstrated in vitro at concentrations of total drug that are achieved in vivo.
      Moreover, dose-dependent total systemic clearance has been described when FAA has
      been administered as a short iv infusion. When administered as a prolonged 24-hr
      infusion, total FAA (bound plus unbound) plasma pharmacokinetics are well
      described with a first-order two-compartment model. However, measurement of
      unbound FAA intra- and post-intravenous infusion in eight patients revealed a
      twofold increase in fraction of FAA unbound in plasma intrainfusion. We attempted
      to fit pharmacokinetic structural models of varying complexity to the unbound
      concentrations alone and simultaneously to the unbound and bound FAA plasma
      concentrations. The data were adequately described only by a model that
      incorporated simultaneous saturable plasma protein binding and a Michaelis-Menten
      process for elimination. A comparison among models is presented, as well as
      pharmacokinetic parameter estimates for FAA in children. These clinical data are
      consistent with predictions of the clearance model in which both saturable
      protein binding (resulting in a dynamically increasing unbound fraction) and
      saturable elimination (resulting in gradually decreasing unbound intrinsic
      clearance) are operative.

PMID- 8138892
TI  - Physiological pharmacokinetics of solutes in the isolated perfused rat hindlimb:
      characterization of the physiology with changing perfusate flow, protein content,
      and temperature using statistical moment analysis.
AB  - Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused
      rat hindlimb was studied under various conditions using the multiple indicator
      dilution (MID) technique. Statistical moment analysis of the outflow profiles for
      the EB, sucrose, and water were used to define the vascular, extravascular, and
      total water spaces, respectively. The varied perfusion conditions included
      albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow
      rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The
      range of studies undertaken were chosen to represent the variety of conditions
      used in the preparation of both isolated animal and human limbs, the latter being
      particularly important in cytotoxic therapy for recurrent malignant melanoma. The
      distribution volumes of EB, sucrose, and water were dependent on the flow rate
      and the albumin content of perfusate. The normalized variances (CV2) of the
      markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68),
      indicating that some disequilibrium occurs during the capillary exchange of water
      and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a
      suitable perfusate for most studies of the isolated rat hindlimb perfusion. The
      effect of albumin concentration manifests itself only at higher flows.

PMID- 8138893
TI  - Simplified methods for the evaluation of the parameters of the time course of
      plasma concentration in the one-compartment body model with first-order invasion
      and first-order drug elimination including methods for ascertaining when such
      rate constants are equal.
AB  - The many limitations in determining the pharmacokinetic parameters of first-order
      invasion of, and elimination from, the one-compartment body model by the method
      of residuals or by "feathering" C-t data can be minimized by applying the
      simplified methods outlined herein. Comparisons of the apparent volumes of
      distribution, V, calculated on the premises that the Bateman Function represents
      ka > ke or its converse, ke > ka, i.e., flip-flop, can permit a proper choice of
      the correct version. Estimation of ke can be obtained by regression of
      (A0/V)/C(oncentration) on AUCt/C where A0/V is estimable from knowledge of Cmax
      and tmax since A0/V = Cmax eketmax. The ratio of the magnitude of the rate
      constant of invasion to that of elimination, m = ka/ke, is related to ketmax by
      the expression ketmax = ln m/(m - 1) for all possible values of m. A table for
      the determination of m from values of ketmax is given. When bioavailability,
      gamma = Ao/Dose, is known or complete, ke and V can be determined from the
      respective ordinate and abscissa of the intersection of A0/Cmax eketmax and
      Cl(clearance)/ke, both plotted against arbitrary ke values. The two functions may
      not intersect at low values of m due to errored C-t values but the ke value when
      the two curves are closest (kmin) may approximate ke. The intersections of Cmax
      eketmax and keAUCT (AUCtrap) plotted against variable ke values (Method A)
      provide estimates of ke from their abscissa values and A/V from their ordinate
      values when gamma is unknown. Method B appears to give more reliable estimates of
      ke at the kmin of the difference eketmax/ke - AUCT/Cmax, plotted against ke.
      Since kmin of this plot is l/tmax when m = 1, the identity of the m as unity
      underlying the C-t data is indicated when either kmintmax is approximately unity
      or kmin is practically synonymous with l/tmax. This was clearly shown when 12
      constructed m = 1, C-t cases with 10% random error were evaluated by Method B.
      Better estimates were effected by all procedures when the raw C-t data were
      smoothed.

PMID- 8138894
TI  - The importance of modeling interoccasion variability in population
      pharmacokinetic analyses.
AB  - Individual pharmacokinetic parameters may change randomly between study
      occasions. Analysis of simulated data with NONMEM shows that ignoring such
      interoccasion variability (IOV) may result in biased population parameter
      estimates. Particular parameters affected and the extent to which they are biased
      depend on study design and the magnitude of IOV and interindividual variability.
      Neglecting IOV also results in a high incidence of statistically significant
      spurious period effects. Perhaps most important, ignoring IOV can lead to a
      falsely optimistic impression of the potential value of therapeutic drug
      monitoring. A model incorporating IOV was developed and its performance in the
      presence and absence of IOV was evaluated. The IOV model performs well with
      respect to both model selection and population parameter estimation in all
      circumstances studied. Analysis of two real data examples using this model
      reveals significant IOV in all parameters for both drugs and supports the
      simulation findings for the case that IOV is ignored: predictable biases occur in
      parameter estimates and previously nonexistent period effects are found.

PMID- 8138895
TI  - Tranylcypromine does not enhance the effects of amitriptyline on 5-HT2 receptors
      in rat cerebral cortex.
AB  - The combination of amitriptyline (a tricyclic antidepressant) and tranylcypromine
      (a monoamine oxidase inhibitor) has been reported to be effective for treatment
      of refractory depressed patients. In the study reported here, this drug
      combination was compared with amitriptyline administered alone on the number and
      affinity of 5-HT2 receptors in rat brain. Male Sprague-Dawley rats were given
      vehicle (distilled water), amitriptyline (3.5 mg/kg/day), or tranylcypromine and
      amitriptyline (0.5 and 3.5 mg/kg/day, respectively) in combination subcutaneously
      via osmotic minipumps for 4, 10, or 28 days. A membrane fraction prepared from
      whole cortex was employed for studying binding to 5-HT2 receptors ([3H]ketanserin
      as the radioligand). The combination of amitriptyline and tranylcypromine
      produced a small but significantly greater down-regulation (decrease in number)
      of 5-HT2 sites than did amitriptyline alone after 10 days of administration; at 4
      and 28 days, both amitriptyline and the drug combination had produced down
      regulation, but there was not a significant difference between the two
      treatments. These data suggest that the antidepressant efficacy observed with
      this combination is not likely due to an enhanced effect on 5-HT2 receptors.

PMID- 8138896
TI  - Sustained-release oral delivery of theophylline by use of polyvinyl alcohol and
      polyvinyl alcohol-methyl acrylate polymers.
AB  - Crystalline polyvinyl alcohol (PVA) polymer and low-crystallinity polyvinyl
      alcohol-methyl acrylate copolymer (PVA-MA) were examined as sustained-release
      tablet excipients with theophylline as a model drug. By blending of different
      proportions of the crystalline polymer and the low-crystallinity copolymer, it
      was possible to affect the release characteristics of the tablets. Tablets made
      with crystalline PVA provided instant release of theophylline in vitro. Tablets
      made with a larger proportion of PVA-MA relative to PVA provided a very prolonged
      release profile in vitro. A formulation containing PVA-MA:PVA:theophylline in a
      ratio of 1:9:10 provided sustained-release profiles in vitro and in vivo in dogs.
      The dissolution release profile of this PVA-blend tablet formulation in vitro
      agreed extremely well with the percentage of bioavailable dose absorbed over time
      in vivo. The formulation provided a plateau of levels in plasma over 16 h. The
      oral bioavailability of theophylline from this formulation in dogs was
      approximately 80% and was equivalent to that obtained after administration of
      Theo-Dur, a marketed extended-release theophylline tablet from Key
      Pharmaceuticals.

PMID- 8138897
TI  - Development of secondary sex characteristics in male rats after fetal and
      perinatal cimetidine exposure.
AB  - Cimetidine has been reported to cause antiandrogenic effects in male pups of
      female rats receiving cimetidine during gestation. Because of conflicting reports
      of cimetidine causing permanent antiandrogenic effects in male rats, we studied
      the sexual development of male rats born to females receiving cimetidine. Water
      or water and cimetidine (194 mg/kg of body weight per day) were administered to
      pregnant rats from day 12 of gestation through weaning. A total of 130 male pups
      were studied. Testicular prostate gland/seminal vesicle weights, anogenital
      distance, serum testosterone and dihydrotestosterone levels, and seminiferous
      tubule areas were compared between the two groups. Transfer of cimetidine across
      the placenta and though breast milk was confirmed by HPLC analysis of serum from
      female littermates at 0, 10, and 20 days of age. With the exception of a smaller
      anogenital distance (p < 0.03) and a lower anogenital index (p < 0.05) in the
      cimetidine-exposed newborn rats, no statistically significant differences were
      observed in the measured parameters between the cimetidine-exposed and control
      groups. Cimetidine exposure during the fetal and perinatal periods did not alter
      the development of secondary sex characteristics in male rat pups.

PMID- 8138898
TI  - A computer program for calculating distribution parameters for drugs behaving
      nonlinearly that is based on disposition decomposition analysis.

PMID- 8138899
TI  - Estimation of the molecular weight of an interacting chlorpheniramine maleate
      salicylamide system from dissolution rate data.

PMID- 8138900
TI  - Comparisons of detections, stabilities, and kinetics of degradation of
      hymecromone and its glucuronide and sulfate metabolites.

PMID- 8138901
TI  - Soft drugs. 17: Quantitative structure-activity relationships of soft
      anticholinergics based on methatropine and methscopolamine.

PMID- 8138902
TI  - Quantitative in vivo iontophoretic studies.
AB  - An experimental methodology was developed to evaluate the physicochemical basis
      for in vitro-in vivo correlations in iontophoretic delivery situations. This
      experimental methodology can be used to quantitatively evaluate the extent of
      interaction between chemical permeation enhancers and iontophoresis for drug
      delivery. The inherent advantages of using Ag/AgCl electrodes are fully exploited
      to control pH and minimize depletion of permeant during prolonged periods of
      iontophoresis.

PMID- 8138903
TI  - Factors controlling the buoyancy and gastric retention capabilities of floating
      matrix capsules: new data for reconsidering the controversy.
AB  - Optimized floating (F) and non-floating (NF) hydrophilic matrix capsules have
      been characterized in vitro with regard to their buoyancy or non-buoyancy
      capabilities and their diametral size evolution with time. The gastric residence
      times (GRTs) and transit behaviors of these F and NF forms prepared in small,
      medium, and large sizes were then comparatively examined in fed volunteers
      remaining either upright or supine. The results show that all the optimized F
      forms do lastingly float upon the gastric contents, whereas the NF forms sink
      rapidly after ingestion. In upright subjects, the F forms are consequently
      protected against postprandial emptying. The GRTs of the NF forms are much more
      variable and highly dependent on their size (mean GRT small < medium < large
      units, p < 0.05). The GRT prolongation obtained with the F forms when compared
      with the NF ones is hence significantly marked for the small and medium size
      dosage forms (p < 0.05) but not for the large ones (p > or = 0.05). In supine
      subjects, a size effect influences the GRT of both the F and NF forms (p < 0.05).
      The F forms are more often emptied before the NF ones but, size for size, the
      mean GRTs do not differ in the aggregate. These findings, together with
      literature data, are used to explain why a number of former investigations have
      come to contradictory conclusions about the effect of density of an undigestible
      form on GRT. Uncontrolled factors are hiding from disclosure the GRT enhancement
      that should be observed when optimized F forms are used within defined
      conditions.

PMID- 8138904
TI  - Simultaneous in vivo microdialysis in plasma and skeletal muscle: a study of the
      pharmacokinetic properties of levodopa by noncompartmental analysis.
AB  - This in vivo study compared the pharmacokinetics of intravenously (iv)
      administered levodopa (L-dopa) in plasma and skeletal muscle. For this purpose, a
      single iv dose of L-dopa (25 mg/kg) was given to an anesthetized beagle dog, and
      L-dopa as well as its O-methyl metabolite, 3-O-methyldopa (3-OMD), were monitored
      in plasma and skeletal muscle simultaneously by microdialysis. The plasma and
      muscle dialysates were continuously collected during a 3-h period after the iv
      administration of the drug. The pharmacokinetic variables were then compared in
      both tissues with noncompartmental modeling. The mean maximum concentration
      (Cmax) for L-dopa in plasma was 173.10 +/- 9.85 ng/mL, whereas in skeletal muscle
      extracellular fluid, it was 14.56 +/- 2.27 ng/mL. The area under the curve of
      concentration versus time from time zero to infinity (AUC0- > inf) values for L
      dopa were 20 times higher in plasma compared with muscle. The difference in half
      life between the two tissues probably indicated the large contribution of the
      distribution phase in either or both tissues over the 3-h time interval.
      Interestingly enough, the AUC0- > 3h values for 3-OMD were within the same range
      in both tissues. These data demonstrated that over a period of 3 h, no
      distribution equilibrium for L-dopa was reached over the two tissues. The very
      low L-dopa/3-OMD ratios suggested that, in contrast to L-dopa, 3-OMD is
      accumulating in skeletal muscle. Whether these findings have any implication for
      the therapeutic response to L-dopa in Parkinson's disease remains to be
      determined.

PMID- 8138905
TI  - A comparative in vitro study of transdermal absorption of antiemetics.
AB  - Transdermal absorption of a series of antiemetics (alizapride, bromopride,
      clebopride, domperidone, metoclopramide, metopimazine, and scopolamine) was
      studied in vitro with the skin of hairless rats as the membrane. The aim of the
      study was to determine the permeation parameters [transdermal permeability rate
      constant (Kp), lag time, and flux] as a measure of the intrinsic permeability of
      these drugs across the skin, with a view to predicting their potential
      therapeutic formulation in Transdermal Therapeutic Systems. A linear correlation
      was established between the log Kp values corresponding to the antiemetics
      studied and their melting point (r = 0.8120, p < 0.05). The logarithm of Kp for
      the antiemetics studied can be predicted from the logarithm of the intrinsic
      partition coefficient (n-octanol-water) by a parabolic function (r = 0.9284, p <
      0.01). Bromopride showed the shortest lag time (19.73 h), whereas clebopride was
      the most suitable drug as a candidate for formulation in transdermal delivery
      systems.

PMID- 8138906
TI  - Pharmacokinetics of indomethacin octyl ester (prodrug) and indomethacin produced
      from the prodrug.
AB  - A prodrug of indomethacin, indomethacin octyl ester (IM-OE), was synthesized and
      its pharmacokinetics was investigated in rat. To describe the time course of the
      plasma indomethacin and IM-OE after intravenous (iv) and oral administrations, a
      pharmacokinetic model with four compartments was developed. Indomethacin rapidly
      appeared in plasma after iv administration of IM-OE and declined in a
      monoexponential manner, with a rapid decline and low plasma levels of IM-OE. The
      plasma concentrations of indomethacin after oral administration of IM-OE were
      much lower than those after oral administration of indomethacin. The high
      concentrations of IM-OE compared with indomethacin were detected in liver 3 h
      after oral dosing of the prodrug, although IM-OE was not detected in plasma. A
      good fit was obtained between the observed and calculated curves based on the
      model, which includes a conversion rate constant of IM-OE to indomethacin for
      both iv and oral dosings of IM-OE. Additionally, the model could successfully
      describe the plasma concentration versus time profiles after indomethacin
      dosings.

PMID- 8138907
TI  - Pharmacokinetics of multiparticulate sustained-release diltiazem preparations in
      dogs.
AB  - The in vivo performance of multiparticulate sustained-release diltiazem
      preparations [HER-SR(A,B,C)] coated with water-insoluble polymer
      (ethylcellulose), to control the in vitro dissolution rate, was evaluated in
      dogs. With a decrease in dissolution rate, HER-SR maintained sustained-release
      characteristics, although the bioavailability decreased slightly. The
      bioavailability of HER-SR(A,B,C) was comparable with that of a conventional
      diltiazem tablet (HER). Plasma diltiazem concentrations for the HER-SR
      preparations were analyzed with a two-fraction absorption model and the
      pharmacokinetic characteristics were discussed. From the results, it was
      considered that HER-SR(B) preparation had desirable pharmacokinetic
      characteristics as sustained-release diltiazem preparations. The absorption site
      of the slow-release component of HER-SR(B) in the gastrointestinal tract was
      examined. Almost all of the component had reached the colon within 5 h of
      administration, the diltiazem content remaining in the component being
      approximately 60% of the initial amount. Thus, it was shown that the HER-SR(B)
      preparation had particular absorption characteristics that resulted in the colon
      being the part of the gastrointestinal tract most receptive to its release. In
      vivo release profiles of diltiazem from the HER-SR(B) preparation were calculated
      by the Wagner-Nelson method, and in vitro and in vivo release profiles of HER
      SR(B) were further analyzed with a two-fraction release equation. A close
      correlation of in vitro and in vivo release profiles of HER-SR(B) was found.

PMID- 8138908
TI  - Measurement of temafloxacin in human scalp hair as an index of drug exposure.
AB  - Scalp hair samples were obtained at 1-month intervals up to 3 months from healthy
      male volunteers participating in a phase I study of a new antimicrobial
      quinolone, temafloxacin. Hair was sectioned into 1-cm lengths from the scalp end.
      After corresponding portions from 10 pieces of hair were dissolved in 1 N NaOH,
      temafloxacin was extracted by chloroform and measured by HPLC equipped with
      fluorescence detection (excitation and detection wavelengths, 280 and 460 nm,
      respectively). In all subjects taking a single oral dose (600 mg; n = 6) or
      repeated oral doses (900 mg/day, b.i.d., for 6.5 days; total, 5850 mg; n = 6),
      the drug was detected in hair. The 1-cm length of hair, in which temafloxacin was
      peaked, was shown to move at the rate of 1 to 1.3 cm/month when the hair of
      growing stage was analyzed. The largest sum of the concentrations of temafloxacin
      found in any set of measurements in hair in each subject was 31.7 +/- 15.0 (mean
      +/- SD, n = 6) and 226.3 +/- 99.4 ng/mg hair (n = 6) for the single and repeated
      doses, respectively. The drug concentration in hair increased by a factor of 7.1,
      whereas the ratios between the single and repeated doses were 9.8, 1.3, and 10.7
      for the total given dose, observed maximal plasma concentration (Cmax), and area
      under the plasma concentration curve, respectively. It was obvious that the Cmax
      was the least likely factor determining temafloxacin concentration in
      hair.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138909
TI  - Adenosine receptor prodrugs: synthesis and biological activity of derivatives of
      potent, A1-selective agonists.
AB  - 5'-Ester derivatives of the potent adenosine agonists N6-[4-[[[[4-[[[(2
      acetylaminoethyl)amino]carbonyl]methyl] anilino]carbonyl]methyl]phenyl]adenosine
      (N-AcADAC; 1) and N6-cyclopentyladenosine (CPA; 2) were prepared as prodrugs.
      Both alkyl esters or carbonates (designed to enter the brain by virtue of
      increased lipophilicity) and 1,4-dihydro-1-methyl-3
      [(pyridinylcarbonyl)oxy]esters designed to concentrate in the brain by virtue of
      a redox delivery system were synthesized. In the 5'-blocked form, the adenosine
      agonists displayed highly diminished affinity for rat brain A1-adenosine
      receptors in binding assays. The dihydropyridine prodrug 29 was active in an
      assay of locomotor depression in mice, in which adenosine agonists are highly
      depressant. The behavior depression was not reversible by peripheral
      administration of a non-central nervous system active adenosine antagonist. In an
      assay of the peripheral action of adenosine (i.e., the inhibition of lipolysis in
      rats), the parent compounds were highly potent and the dihydropyridine prodrug
      was much less potent.

PMID- 8138910
TI  - Injectable polyanhydride granules provide controlled release of water-soluble
      drugs with a reduced initial burst.
AB  - A method for preparing polyanhydride granules of an injectable size was
      developed. The resulting granules permitted a nearly constant release of low
      molecular-weight, water-soluble drugs without an initial burst. The
      polyanhydrides used were poly(fatty acid dimer), poly(sebacic acid), and their
      copolymers. The dyes acid orange 63 and p-nitroaniline were used as model
      compounds for drugs. Polymer degradation and drug release for disks and variously
      sized granules of copolymers containing drugs, prepared by a water-in-oil (W/O)
      emulsion method, were compared with those for devices prepared by the usual
      compression method. In the W/O emulsion method, a mixture of aqueous drug
      solution and polymer-chloroform solution was emulsified by probe sonication to
      prepare a very fine W/O emulsion. The powder obtained by freeze-drying of the W/O
      emulsion was pressed into circular disks. In the compression method, the drug was
      mechanically mixed with the polymer, and the mixture was compressed into circular
      disks. The resulting disks were ground to prepare granules of different sizes.
      The granules encapsulated more than 95% of the drug, irrespective of the
      preparation method. Both methods were effective in preparing polymer disks
      capable of controlled drug release without any initial burst. However, as the
      granule size decreased to an injectable size (diameter, < 150 microns), a large
      difference in the drug release profile was observed between the two preparation
      methods. The injectable granules obtained by the W/O emulsion method showed
      nearly constant drug release without any large initial burst, in contrast to
      those prepared by the compression method, irrespective of the drug type.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138911
TI  - Solubilities and solvation of aluminum(III), iron(III), and indium(III) 8
      hydroxyquinolinates in methanol/water mixtures.
AB  - Solubilities are reported for aluminum, indium, and iron(III) complexes of 8
      hydroxyquinoline and its 5-nitro, 5-sulfonato, and 7-iodo-5-sulfonato derivatives
      in water, methanol, and water/methanol mixtures, at 298.2 K. Transfer chemical
      potentials for the respective complexes have been derived from these data, and
      their trends are discussed in terms of solvation of the complexes by water and
      methanol.

PMID- 8138912
TI  - Pharmacodynamics of the hydrolysis-activation of the cardioprotective agent (+)
      1,2-bis(3,5-dioxopiperazinyl-1-yl)propane.
AB  - The hydrolysis of the cardioprotective agent ICRF-187 [(+)-1,2-bis(3,5
      dioxopiperazinyl-1-yl)propane] to its presumed active form under conditions of
      physiologic pH and temperature were followed by HPLC chromatography. Successful
      chromatography of all of the hydrolysis products required the use of EDTA in the
      aqueous eluant to prevent metals in the HPLC flow system from binding to the
      strongly metal ion-binding product ADR-925. The kinetics of the hydrolysis was
      followed to approximately 200 h. The ring closest to the methyl group on ICRF-187
      was observed to open at about twice the rate of the other ring. This product
      accumulates in the reaction mixture not only because it is produced more quickly
      but also because it decays more slowly. ICRF-187 is lost from the reaction
      mixture with a half-life of 9.3 h, whereas the final hydrolysis product ADR-925
      is produced with a half-life of 23.0 h. Rate constants for ring opening to one
      ring and two-ring opened hydrolysis products were obtained with a reaction scheme
      that assumed parallel and consecutive first-order reactions for these steps.

PMID- 8138913
TI  - Electron spin resonance study of radiosterilization of antibiotics: ceftazidime.
AB  - Fundamental information on radiosterilization of ceftazidime was obtained by
      electron spin resonance (ESR) measurement of free radicals produced in gamma-ray
      irradiated ceftazidime at 4.2-295 K. Three types of free radicals are produced by
      gamma-irradiation. The first one shows septet lines in an ESR spectrum and decays
      at 230 K: it is assigned as a .C(CH3)2COOH radical. The second one shows triplet
      lines and decays at 293 K: it is assigned as iminoxyl radicals (> C = N-O.). The
      third one shows a broad singlet line and survives even at 295 K. The plausible
      assignment of this spectrum is discussed. It is concluded that an O-C bond of the
      gamma-irradiated ceftazidime is ruptured, producing the iminoxyl radicals and
      .C(CH3)2COOH radicals. The yields of free radicals increase linearly with the
      increasing dose of gamma-irradiation up to 10 kGy at 295 K as well as 77 K. Half
      of the radicals that show a broad singlet line survive at 295 K upon storage of
      the irradiated ceftazidime for 159 days. It is concluded that the ESR measurement
      of free radicals gives a good method for discrimination of irradiated antibiotics
      from non-irradiated ones and an estimation of an irradiation dose.

PMID- 8138914
TI  - Preparation of drug-carrier emulsions stabilized with phosphatidylcholine
      surfactant mixtures.
AB  - A method has been developed to produce lipid emulsion particles for parenteral
      use as drug carriers. The technique uses a mixture of a triacylglycerol oil and
      purified egg yolk phosphatidylcholine (EPC) as the basic system and sonication
      under mild conditions to produce the emulsion. A large number of mild
      "biological" surfactants were tested for their ability to improve the dispersing
      and stability properties of the basic system. The results showed a preference for
      polysorbate 80, and a suitable combination of oil and emulsifiers was found to be
      castor oil:EPC:polysorbate 80 (1:0.4:0.12, weight ratios). Repeated preparation
      of this emulsion system in phosphate-buffered saline (PBS) gave particles with a
      mean diameter near 50 nm, in a reproducible way and with a low polydispersity.
      The stability of the emulsion was very good (> 3 months), both in PBS and in 2.5%
      glycerol. The method was also tested with two lipophilic anticancer drugs, which
      were solubilized in castor oil, with satisfactory results. The lipid emulsion
      particles described in this study also have a potential use as targetable
      carriers for site-specific drug delivery.

PMID- 8138915
TI  - Cyclization reactions leading to beta-hydroxyketo esters.
AB  - The purpose of the research was to synthesize beta-diketo esters and to evaluate
      them for anticonvulsant activity. The reaction of methyl vinyl ketone with
      dimethyl malonate in the presence of potassium carbonate gave an uncyclized
      product that underwent a Claisen condensation to yield methyl 2-hydroxy-4
      oxocyclohex-2-en-1-oate (5a). Similarly, other cyclized beta-hydroxyketo esters
      were prepared, and their spectrometric data confirmed that the enol tautomers
      were preferred to the beta-diketo tautomers. The synthetic work clarified the
      reaction pathway for the Michael addition of malonate esters to enones. Of the
      intermediates and products tested for anticonvulsant activity, dimethyl 2,2-bis
      (3-oxobutyl)malonate (9a) was found to possess anticonvulsant property. However,
      it is emphasized that the beta-hydroxyketo esters could be useful intermediates
      in the synthesis of enaminone anticonvulsants.

PMID- 8138916
TI  - Synthesis, reactions, and preliminary evaluations of enaminone esters.
AB  - The objective of this work was to design enaminone esters that would possess
      potential medicinal properties. The reaction between beta-hydroxyketo esters and
      primary or secondary amines yielded secondary or tertiary enaminone esters,
      respectively. The UV spectra of the enaminone esters were determined in acidic,
      alkaline, and neutral media; the spectra have a hypsochromic shift in acidic
      media in comparison with neutral media. The enaminone esters provided
      nucleophilic and electrophilic sites for a variety of reactions. Thus, the
      enaminone esters were converted into enaminone amides and O-alkylation products
      exclusively. Although the enaminone esters were generally resistant to reduction
      by metal hydrides, one unhindered enaminone ester was reduced to an alcohol with
      sodium borohydride. Another enaminone ester reacted with guanidine to give the
      corresponding quinazolinone. Due to the variety of nucleophilic and electrophilic
      sites in the enaminone system, enaminone esters possess a great potential as
      reaction intermediates and medicinal compounds. Preliminary evaluations of the
      enaminone esters revealed a histaminergic effect, uterine relaxant properties,
      and anticonvulsant activity.

PMID- 8138917
TI  - Effects of four penetration enhancers on corneal permeability of drugs in vitro.
AB  - The usefulness of penetration enhancers in promoting drug permeation across the
      cornea was investigated for drugs varying from hydrophilic to lipophilic. Four
      purported penetration enhancers [Azone (laurocapram), hexamethylenelauramide,
      hexamethyleneoctanamide, and decylmethylsulfoxide] were employed. Corneal
      permeability coefficients of drugs that were either hydrophilic (acetazolamide,
      cimetidine, guanethidine, and sulfacetamide), moderately lipophilic (bunolol and
      prednisolone), or lipophilic (flurbiprofen and its amide analogue) were measured
      in the absence or in the presence of various Azone concentrations. The effects of
      penetration enhancers on the corneal penetration of cimetidine were also
      compared. The corneal penetration of hydrophilic compounds was enhanced by at
      least 20-fold at 0.1% Azone. For prednisolone and bunolol, the maximal
      enhancement was at 0.025-0.1% Azone and was marginal (two- to 5-fold), whereas
      Azone inhibited rather than enhanced the corneal penetration of the lipophilic
      flurbiprofen and its amide analogue. All four enhancers behaved similarly in
      enhancing corneal penetration of cimetidine and corneal hydration after
      incubation in vitro. Possible mechanisms of penetration enhancers on corneal drug
      penetration were discussed. Penetration enhancers may have clinical benefits in
      improving ocular drug delivery of hydrophilic compounds, however, their utility
      may depend on the toxicological profiles.

PMID- 8138918
TI  - Deformation kinetics of potassium bromide crystals predict tablet stress
      relaxation.
AB  - A model relating the interparticulate contact stress within a tablet matrix with
      the compaction stress was developed previously to permit the nonlinear
      deformation kinetic analysis of the viscoelastic behavior of pharmaceutical
      tablets with the known properties of the tablet constituents. The present
      research was undertaken to determine whether the inverse operation (i.e., using
      tablet stress relaxation to determine single crystal properties) was possible.
      The stress relaxation of potassium bromide (KBr) compacts was evaluated as a
      function of temperature and relative density, and an attempt was made to
      calculate the deformation kinetic parameters. The stress relaxation of KBr did
      not fit the model under ambient conditions for two reasons: (1) KBr has two slip
      systems with approximately the same shear stress at room temperature; and (2) KBr
      strain-hardens. When these complications were taken into consideration, the
      stress relaxation behavior could be explained. Therefore, whereas single crystal
      tests are capable of yielding parameters that can be used to predict compact
      behavior, the inverse process of quantifying fundamental material parameters from
      compact behavior is problematic due to the difficulty of determining, a priori,
      all the processes that operate simultaneously.

PMID- 8138919
TI  - Pharmacokinetics of 2',3'-dideoxy-5-fluoro-3'-thiacytidine in rats.
AB  - Although several drugs have shown clinical anti-human immunodeficiency virus
      activity, reduced activity with long-term use and toxicity make new agents with
      high therapeutic indices desirable. Racemic cis-2',3'-dideoxy-5-fluoro-3'
      thiacytidine (FTC) is a new synthetic nucleoside analogue that is usually potent
      against human immunodeficiency virus types 1 and 2 and hepatitis B virus in
      vitro. The purpose of this study was to characterize the preclinical
      pharmacokinetics of FTC in rats. Rats were administered 10, 50, and 100 mg of FTC
      per kg of body weight intravenously. Concentrations of FTC in plasma and urine
      were determined by HPLC. Pharmacokinetic parameters were generated by area/moment
      analysis. Plasma FTC concentrations declined rapidly in a biexponential fashion,
      with a terminal half-life of approximately 2 h. The area under the plasma FTC
      concentration-time curve increased proportionally with increasing dose, and there
      were no statistically significant differences in pharmacokinetic parameters among
      the three doses. Thus, the disposition of FTC was independent of dose over the
      range of 10-100 mg/kg. Since the disposition of FTC was linear, pharmacokinetic
      parameters were averaged for the three doses. The average total clearance of FTC
      was 1.91 +/- 0.32 L/h/kg (mean +/- SD), the average renal clearance was 1.08 +/-
      0.26 L/h/kg, and the average nonrenal clearance was 0.83 +/- 0.27 L/h/kg.
      Approximately 55% of the dose of FTC was recovered as unchanged drug in the
      urine. The steady-state volume of distribution of FTC averaged 2.17 +/- 0.59
      L/kg.

PMID- 8138920
TI  - Interaction of the stereoisomers of basic drugs with the uptake of
      tetraethylammonium by rat renal brush-border membrane vesicles.
AB  - Stereoselectivity in the renal clearance of drugs may be due to a stereoselective
      interaction with the organic cation/proton antiporter in the brush-border
      membrane of renal tubular epithelial cells. The interaction of the stereoisomers
      of chiral basic drugs with the uptake of [14C]tetraethylammonium was studied in
      rat renal brush-border membrane vesicles. No differences were observed in
      inhibition of [14C]tetraethylammonium uptake between the enantiomers of pindolol,
      disopyramide and bupivacaine or between (+/-)- and (+)-hydroxychloroquine and
      quinine/quinidine. Stereoselectivity was observed for the enantiomers of
      verapamil (IC50, R-verapamil 5.9 +/- 1.7 microM; S-verapamil, 3.4 +/- 1.7
      microM). Stereoselectivity was also observed with the four stereoisomers of
      norephedrine and ephedrine in which the pairs of enantiomers differing in
      configuration at the carbon atom adjacent to the nitrogen atom showed
      stereoselectivity whereas those enantiomers having the same configuration at this
      carbon atom showed lack of stereoselectivity. It is concluded that when the
      center of chirality is adjacent to the basic functional group, the interaction
      with the transporter for organic cations is stereoselective. Further studies are
      required to elucidate the relationship between substrate stereochemistry and the
      organic cation transporter at both the basolateral and brush-border membranes of
      the renal tubular epithelial cells.

PMID- 8138921
TI  - A unique central cholinergic deficit in the spontaneously hypertensive rat:
      physostigmine reveals a bradycardia associated with sensory stimulation.
AB  - Using a sensory stimulation (startle) paradigm in normotensive and hypertensive
      rats, we evaluated the contribution of central cholinergic mechanisms to the
      pathology of hypertension. In normotensive Wistar-Kyoto (WKY) rats, transient
      airpuff stimuli elicit a complex startle reaction consisting of several
      behavioral and autonomic components. These include jumping (motor response), an
      increase in blood pressure (pressor response), an early-trial decrease in heart
      rate (bradycardia) and a later-trial increase in heart rate (tachycardia).
      Intracerebroventricular (i.c.v.) administration of cholinergic compounds to WKY
      rats primarily altered the bradycardia component. Thus, depletion of brain
      acetylcholine with hemicholinium-3 (5 micrograms/kg i.c.v.) abolished bradycardia
      responses without significantly affecting the motor response, tachycardia or
      pretest cardiovascular base-line parameters. Furthermore, enhancement of brain
      acetylcholine with acetylcholinesterase inhibition (physostigmine, 50
      micrograms/kg i.c.v.) enhanced bradycardia in WKY rats. The nonspecific
      muscarinic antagonist scopolamine and the M1 muscarinic receptor antagonist
      pirenzepine, but neither the M2 muscarinic antagonist methoctramine nor the
      nicotinic antagonist hexamethonium, attenuated bradycardia. We conclude that a
      central M1 muscarinic receptor participates in the control of startle-associated
      bradycardia in the WKY rat. The spontaneously hypertensive rat does not normally
      exhibit startle-associated bradycardia. Because i.c.v. physostigmine revealed
      early-trial bradycardia in this strain, we conclude that a selective central
      cholinergic deficit contributes to a suppression of startle-associated
      bradycardia in the spontaneously hypertensive rats.

PMID- 8138922
TI  - Characterization of canine renal endothelin receptor subtypes and their function.
AB  - Binding and renal functional studies were conducted to characterize endothelin
      (ET) receptors in the dog kidney. Binding studies that were performed in renal
      cortical membranes by using [125I]-ET-1 and [125I]-ET-3 and the ETA- and ETB
      selective ligands, BQ123 (cyclo [D-Trp-D-Asp-L-Pro-D-Val-L-Leu]) and sarafotoxin
      6c (S6c), respectively, revealed that the ratios of ETA to ETB receptors in
      cortical, medullary and papillary membranes were 22:78, 39:61 and 50:50,
      respectively. In vivo studies in the anesthetized dog demonstrated that an
      intrarenal artery infusion of ET-1 (0.3-10 ng kg-1 min-1) resulted in a dose
      dependent decrease in renal blood flow (RBF) and glomerular filtration rate
      (GFR). At a dose of 10 ng kg-1 min-1 of ET-1, RBF and GFR decreased by 82 +/- 6%
      and 89 +/- 6%, respectively. An infusion of BQ123 (10 micrograms kg-1 min-1) into
      the renal artery resulted in a significant inhibition of the ET-1-induced renal
      vasoconstriction. At identical doses as ET-1, S6c had little effect on either RBF
      (-3 +/- 6%) or GFR (-6 +/- 16%). ET-1 decreased urine flow and had little effect
      on fractional sodium excretion, whereas S6c increased both urine flow and
      fractional sodium excretion. These data indicate that ET-1-induced renal
      vasoconstriction in the dog is mediated by ETA receptors; however, ETB receptor
      stimulation may inhibit sodium reabsorption.

PMID- 8138923
TI  - Agonist-induced desensitization and loss of high-affinity binding sites of stably
      expressed human 5-HT1A receptors.
AB  - Exposure of HeLa cells stably expressing cloned human 5-hydroxytryptamine (5
      HT)1A receptors (HA7 cells) to the agonist 8-hydroxy-2-(di-N-propylamino)
      tetralin (8-OH-DPAT) results in a loss of high-affinity binding sites and a
      desensitization of receptor-adenylate cyclase coupling, as measured by 5-HT1A
      mediated inhibition of forskolin-stimulated adenylate cyclase activity. These
      responses can also be observed after exposure to forskolin, which activates
      cyclic AMP-dependent protein kinase A or after treatment with known activators of
      protein kinase C (PKC) such as phorbol-12-myristate 13-acetate (PMA). The
      responses elicited by exposure to 8-OH-DPAT or PMA can be blocked completely by
      inhibitors of PKC and also by 24-hr exposure to PMA. Preincubation of HA7 cells
      with 8-OH-DPAT also stimulates hydrolysis of inositol phospholipids and the
      production of arachidonic acid. Inhibition of phospholipase A2 with quinacrine or
      by removal of extracellular Ca++ blocks the agonist-mediated loss of 5-HT1A
      receptor binding sites. These data demonstrate that agonist-induced down
      regulation of the 5-HT1A receptor occurs after stimulation of both the PKC and
      phospholipase A2 signaling pathways, both of which may activate PKC. The
      subsequent response is a loss of high-affinity ligand binding sites and
      functional receptor coupling to adenylate cyclase.

PMID- 8138924
TI  - Peroxynitrite, a product of superoxide and nitric oxide, produces coronary
      vasorelaxation in dogs.
AB  - The vascular effect of peroxynitrite (ONOO-), a product of superoxide anion and
      nitric oxide, in isolated canine coronary arteries bathed in a 10 mM 4-(2
      hydroxyethyl)-1-piperazineethanesulfonic acid-buffered physiological salt
      solution (pH 7.4) was investigated. ONOO- was synthesized from nitrite and H2O2
      in a quenched-flow reactor. Addition of 0.01 to 30 microM ONOO- produced a rapid,
      dose-dependent relaxation in all 17 rings of coronary arteries with a threshold
      concentration of 0.1 microM, IC50 of 1.0 +/- 0.1 microM and Emax of -96 +/- 0.5%
      (Means +/- S.E.M.). Incubation of arteries in a standard bicarbonate-buffered
      Krebs-Henseleit solution decreased slightly the sensitivity of ONOO- relaxation
      but did not alter the maximum effect (Emax = -97 +/- 1.1, n = 6 vessels). The
      ONOO(-)-induced coronary relaxation was reversible upon washing, and was also
      reproducible with repeated testings in the same ring. Mechanical removal of
      intimal endothelium did not alter the observed relaxant effect. Addition of
      superoxide dismutase (100 U/ml) potentiated the ONOO- relaxation by shifting the
      dose-response curve to the left (IC50 = 0.4 +/- 0.1 microM, P < .05, n = 17),
      whereas 3 microM hemoglobin inhibited it by shifting the curve to the right (IC50
      = 20 +/- 4 microM, P < .05, n = 15). Relaxation was also observed with higher
      concentrations of sodium nitrite and decomposed ONOO-, although the time course
      of the development of these relaxations was considerably slower and with reduced
      sensitivity. In addition, superoxide dismutase had no effect on the latter
      relaxation responses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138925
TI  - Pharmacological characterization of a potent nonpeptide endothelin receptor
      antagonist, 97-139.
AB  - The endothelin (ET) receptor antagonist activity of 97-139 [27-O-3-[2-(3-carboxy
      acryloylamino)-5-hydroxyphenyl]-acryloylo xy myricerone, sodium salt] was
      studied. In rat aortic smooth muscle A7r5 cells that express ETA receptors and
      human Girardi heart cells that express ETB receptors, 97-139 displaced
      specifically bound [125I]ET-1 with the Ki values of 1.0 +/- 0.2 and 1000 +/- 200
      nM, respectively. The compound caused a concentration-dependent inhibition of ET
      1-induced increases in intracellular Ca++ levels in A7r5 cells, but not in
      Girardi heart cells. 97-139 also inhibited ET-1-induced [3H]thymidine
      incorporation in A7r5 cells (IC50 = 0.92 +/- 0.48 nM). In rat aortic rings, 97
      139 produced parallel rightward shifts in the ET-1 concentration-response curve
      without affecting the maximal contractile response (pA2 = 8.8 +/- 0.4).
      Administration of 97-139 (0.03-1.0 mg/kg) i.v. to pithed rats resulted in dose
      dependent inhibition of the pressor response to ET-1. The in vivo potency of 97
      139 was almost the same as that of BQ-123, although the potencies of 97-139 in
      binding assays and in vitro functional assays were about one order of magnitude
      higher than those of BQ-123. This discrepancy might involve high binding toward
      albumin in plasma because 95% plasma and 4% albumin reduced the apparent binding
      affinity of 97-139 by 22- to 24-fold, but not of BQ-123.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8138926
TI  - Acute immunosuppressive effects of morphine: lack of involvement of pituitary and
      adrenal factors.
AB  - We have previously reported that morphine inhibits Concanavalin A-stimulated
      blood lymphocyte proliferation in a dose-dependent manner. Maximal (80%)
      inhibition by morphine occurred with a dose of 10 mg/kg 2 hours after drug
      administration. Concurrent with this suppressive effect was a 2- to 4-fold
      increase in plasma corticosterone concentrations. In the present study, we
      examined the potential contribution of the hypothalamic-pituitary-adrenal axis to
      the suppressive effects of acute morphine exposure. To assess the role of
      glucocorticoids, rats were pretreated with the steroid receptor antagonist RU486
      (20 mg/kg) 30 min before morphine (10 mg/kg) administration. A significant
      inhibition of lymphocyte activity occurred with morphine in the absence or
      presence of RU486 pretreatment. Consistent with a mechanism independent of
      glucocorticoids, adrenalectomy also failed to attenuate the inhibitory actions of
      morphine. To examine the potential role of pituitary hormones in the suppressive
      effect, similar experiments were carried out in hypophysectomized animals. In
      sham-operated or hypophysectomized animals, morphine was found to be equally
      effective in suppressing lymphocyte proliferation. These results suggest that
      factors elaborated from intact pituitary or adrenal glands are not required for
      the acute inhibitory effects of morphine on peripheral blood lymphocyte activity.

PMID- 8138927
TI  - A selective blocker for rested T-type Ca++ channels in guinea pig atrial cells.
AB  - The T-type Ca++ channel is widely distributed. Its physiological roles have not
      been well established because of the lack of a selective T-channel blocker. By
      using the suction pipette method, the authors describe (7-[[4-[bis(4
      fluorophenyl)methyl]-1-piperazinyl]methyl]-2-[(2- hydroxyethyl)amino]4-(1
      methylethyl)-2,4,6-cycloheptatrien-1-one) or U-92032, which selectively blocks
      rested closed T-type Ca++ channels (T channel). After a 3-min exposure to
      external U-92032 (1 microM), a 50% resting block of the T channel was observed on
      the first step depolarization from -90 to -40 mV; subsequent stimulations at 0.1
      Hz produced little further block. The L-type Ca++ current (L channel) was not
      affected. At 10 microM, U-92032 produced about 100% resting block of the T and
      20% block of the L channels. Subsequent stimulations at 0.1 Hz increased the
      block of L channel to 56% at the sixth pulse, which indicated strong use
      dependence at negative potentials and low stimulation rates. Blockade of the T
      channel did not alter channel steady-state activation and inactivation or current
      inactivation time courses. By contrast, blockade of the L channel shifted the
      midpoint of its steady-state inactivation curve from -20.6 mV to -27.8 mV and
      accelerated its slow inactivation time course, from 171 +/- 16 msec to 79.8 +/-
      9.3 msec. Moreover, the 90% recovery time from inactivation was increased from
      0.12 to 60 sec. Because U-92032 is ionized at pH 7, its inability to affect the T
      channel gating property may suggest external drug binding sites.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138928
TI  - The influence of desipramine on thyroid hormone metabolism in rat brain.
AB  - The effect of the antidepressant desipramine (DMI) on the activities of the three
      iodothyronine deiodinase isoenzymes involved in the central metabolism of thyroid
      hormones were investigated in 11 brain regions and 3 peripheral tissues in the
      rat. The investigations were carried out at three different times during the
      light/dark cycle: 5 A.M., 1 P.M. and 11 P.M. Interest is focused on changes in
      the two enzymes that catalyze: i) the 5'deiodination of T4 to the biologically
      active T3, i.e., type II 5'deiodinase (5'D-II), and ii) the 5 (or inner-ring)
      deiodination of T3 to the biologically inactive 3,3'T2, i.e., type III 5
      deiodinase (5D-III). Fourteen days' treatment with 20 mg/kg DMI, but not with 5
      mg/kg DMI, induced significant increases in 5'D-II in eight different areas of
      the CNS. The regions affected were identical to those that receive noradrenergic
      input from the locus coeruleus. Even control animals showed a circadian rhythm of
      5'D-II activity in some brain regions, and the effects of DMI also depended on
      the time of death within the 24-hr rhythm. 5D-III was not affected. Serum T4 were
      lower after administration of DMI, most probably because of enhanced tissue
      uptake of T4. This is in line with the corresponding finding in depressed
      patients, indicating that similar changes in both central and peripheral thyroid
      hormone metabolism may occur after antidepressant pharmacotherapy in both humans
      and rats. These data support the hypothesis that interactions with the CNS
      metabolism of the thyroid hormones may be involved in the mechanisms of action of
      DMI.

PMID- 8138929
TI  - Discrimination of A1 versus A2 receptor subtype selectivity of adenosine receptor
      agonists in vivo.
AB  - Previous attempts to discern and quantify the selectivity of agonists for A1
      versus A2 adenosine receptors in vivo have been confounded by the activation of
      baroreceptor reflexes and/or simultaneous expression of responses to both A1 and
      A2 receptor activation. In anesthetized, vagotomized rats with isolated in situ
      constant-flow perfused hindquarters (HQ), bradycardic responses to i.v. agonist
      injections measured A1 receptor activation and HQ vasodilation elicited by i.a.
      agonist injections measured the stimulation of A2 receptors. Adenosine and 5'-N
      ethylcarboxamidoadenosine (NECA) produced A2 receptor-mediated HQ vasodilation at
      doses 8- and 4-fold lower (-log ED50 values, 7.3 +/- 0.04 mol and 8.7 +/- 0.06
      mol, respectively) than those required to evoke A1 receptor-mediated bradycardia
      (-log ED50 values, 6.4 +/- 0.01 mol and 8.1 +/- 0.07 mol, respectively). N6
      cyclopentyladenosine (CPA) was approximately 8-fold selective for A1 receptors (
      log ED50 values, A1, 8.5 +/- 0.05 mol; A2, 7.6 +/- 0.16 mol). 2
      (Phenylamino)adenosine (CV-1808) and 2[2(4-fluorophenyl)ethoxy]adenosine (FPEA)
      were at least 125- and 200-fold more potent agonists at A2 receptors (-log ED50
      values, 7.7 +/- 0.10 mol and 8.0 +/- 0.24 mol, respectively) than at A1 receptors
      (-log ED50 values, 5.6 +/- 0.08 mol and 5.7 +/- 0.01 mol, respectively). These
      studies demonstrated that stimulation of A1 and A2 receptors may be discriminated
      in vivo and that such responses are selective, reproducible, dose-dependent and
      quantifiable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138930
TI  - Ethanol modulates [125I]calmodulin binding to synaptic plasma membranes from rat
      brain.
AB  - The effects of ethanol in vitro on Ca(++)-dependent binding of [125I] calmodulin
      to brain synaptic plasma membranes (SPM) from control and chronically ethanol
      treated rats were studied. In SPM from control animals, ethanol at 50 to 200 mM
      inhibited [125I] calmodulin binding; the inhibition was correlated with a
      decreased membrane affinity for [125I]calmodulin as shown by Scatchard analysis,
      and an increased dissociation of [125I]calmodulin-membrane complexes as shown by
      kinetic analysis. Arrhenius analysis indicates that [125I]calmodulin binding was
      influenced by lipid transition of the membrane, and that ethanol in vitro
      resulted in a shift of the transition temperature toward a lower value. From
      animals receiving chronic ethanol treatment (3 weeks), the SPM were found to be
      resistant to the inhibitory effect of ethanol on binding. The resistance to
      ethanol inhibition was correlated with a higher membrane affinity for
      [125I]calmodulin and a higher transition temperature, as compared with control
      SPM. Because a variety of membrane-bound processes are regulated by calmodulin or
      calmodulin-dependent processes, the inhibitory effect of ethanol on membrane
      binding of calmodulin could lead to a cascade of consequences in synaptic
      function. Moreover, the resistance of the membranes to ethanol inhibition after
      chronic ethanol treatment implies that membrane binding of calmodulin is part of
      the mechanism underlying alcohol tolerance and dependence.

PMID- 8138931
TI  - Kappa agonist and antagonist properties of mixed action opioids in a pigeon drug
      discrimination procedure.
AB  - Previous investigations indicate that mixed action opioids (i.e., opioids with
      activity at a combination of opioid receptor sites or a combination of opioid and
      nonopioid sites) often possess kappa-like stimulus effects in the rat and monkey,
      but mu-like stimulus effects in pigeons. In the present investigation, the kappa
      agonist and antagonist actions of a series of mixed action opioids were examined
      in pigeons trained to discriminate a 0.017-mg/kg dose of the kappa agonist
      bremazocine from saline. The mixed-action opioids (-)-n-allylnormetazocine, (-)
      cyclazocine, (-)-metazocine, levallorphan, buprenorphine, nalbuphine, butorphanol
      and nalorphine failed to substitute for the bremazocine stimulus. When
      administered in combination with the training dose of bremazocine, each of these
      opioids produced a dose-related antagonism of the bremazocine stimulus. With the
      exceptions of butorphanol and (-)-metazocine, the antagonist effects of these
      opioids were surmountable. Buprenorphine, (-)-n-allylnormetazocine and
      levallorphan produced their kappa antagonist effects at doses approximately 2 to
      3 log units lower than those that decreased rates of responding when these
      opioids were administered alone, whereas approximately 1 log unit separated the
      kappa antagonist and rate-decreasing effects of nalorphine, nalbuphine and (-)
      cyclazocine. In contrast, the kappa antagonist effects of butorphanol and (-)
      metazocine were observed only at doses of markedly decreased response rates. A
      somewhat different profile was obtained with ethylketocyclazocine and
      ketocyclazocine in that these mixed action opioids produced partial substitution
      for and partial antagonism of the bremazocine stimulus.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8138932
TI  - The pharmacokinetics and pharmacodynamics of the angiotensin II receptor
      antagonist losartan potassium (DuP 753/MK 954) in the dog.
AB  - The pharmacokinetics and plasma concentration-effect relationship for the
      nonpeptide angiotensin II (Ang II) receptor antagonist losartan potassium
      (losartan) have been determined with conscious and anesthetized dogs. The p.o.
      bioavailability of single doses of 5 to 20 mg/kg was low, 23 to 33%, and
      independent of the dose. Absorption was rapid, with peak plasma levels observed
      within 1 hr, and the Cmax and area under the concentration vs. time curve to
      infinity were proportional to the dose, P < .05. The elimination half-life, 108
      to 153 min, was longer than that observed after a single i.v. dose, 41 min, and
      may reflect both continuous absorption and enterohepatic recirculation because
      the major route of excretion was via the bile. Single i.v. doses were eliminated
      rapidly, with a systemic plasma clearance of 22.2 ml/min/kg. When corrected for
      the blood:plasma distribution ratio, 0.66 to 0.72, the systemic clearance
      approximates hepatic blood flow, suggesting that clearance is primarily via
      hepatic metabolism and biliary excretion. Losartan was not distributed
      extensively to tissues; apparent volume of distribution at steady-state of 0.30
      liters/kg and was highly but not extensively bound to plasma proteins; 2.7 to
      2.9% unbound (free). The plasma concentration vs. blockade of exogenous Ang II
      induced vasopressor response was also determined after a single 3-mg/kg i.v. dose
      of losartan with a sigmoidal Emax model. Blockade of the pressor response was
      rapid, 89% at 5 min, and declined to 11% at 240 min postdose. The relationship
      between concentration and effect was highly significant (r = 0.922, P < .01),
      with an IC50 (total) of 96 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138933
TI  - Somatostatin analog inhibits afferent response to rectal distention in diarrhea
      predominant irritable bowel patients.
AB  - Irritable bowel syndrome (IBS) patients exhibit enhanced sensitivity to rectal
      distention. The somatostatin analog reduces perception of rectal distention in
      healthy volunteers without modifying rectal resistance. We evaluated whether
      octreotide has similar effects on rectal perception and resistance in diarrhea
      prone IBS patients. Octreotide (100 micrograms s.c.) and placebo were injected in
      double-blind fashion in eight IBS patients. Rectal balloons measured volumes that
      evoked increasing levels of perception and intrarectal pressures. After placebo,
      threshold perception, pressure, urgency and maximal tolerated volume were
      reported at 18 +/- 5, 46 +/- 8, 72 +/- 7 and 102 +/- 10 ml by the IBS patients,
      values less than we have observed in healthy volunteers. With octreotide, these
      sensations were perceived at higher volumes (40 +/- 10, 89 +/- 16, 167 +/- 20 and
      202 +/- 25 ml, P < .05) that approximated responses in healthy volunteers. IBS
      patients exhibited higher rectal pressures at each volume and showed a trend to
      higher rectal resistance (0.13 +/- 0.02 mmHg/ml) than we have observed in healthy
      volunteers. These abnormalities were normalized by octreotide. Octreotide did not
      block the rectoanal inhibitory reflex confirming a lack of effect on local rectal
      reflex arcs. As with healthy volunteers, IBS patients with diarrhea experience
      reduced perception of rectal distention after octreotide. Octreotide also reduces
      elevated rectal pressures in IBS patients, in contrast to healthy volunteers.
      Thus, octreotide shows potential therapeutic benefit in IBS via dual effects on
      visceral afferent pathways and rectal wall stiffness.

PMID- 8138934
TI  - Antithetical actions of mitoxantrone and doxorubicin on ryanodine-sensitive Ca++
      release channels of rat cardiac sarcoplasmic reticulum: evidence for a
      competitive mechanism.
AB  - The anthracenedione mitoxantrone (MTX) is examined for activity toward ryanodine
      sensitive Ca++ release channels (i.e., ryanodine receptors; RyR) from rat cardiac
      SR singly or in combination with doxorubicin (DXR). MTX and DXR exhibit
      antithetical activities toward RyR. Under conditions promoting channel closure,
      DXR enhances the binding of [3H]ryanodine (EC50 = 44 microM), whereas MTX has
      higher affinity (EC50 = 25 microM) but > 10-fold lower activity towards
      activating RyR. Unlike DXR, MTX assayed under conditions promoting channel
      activation inhibits the binding of [3H]ryanodine (IC50 = 3.3 microM) and does not
      alter the potency with which Ca++ activates RyR in the presence or absence of
      Mg++. In the presence of Mg++, MTX does not alter kobs and slows k-1 for
      [3H]ryanodine binding, whereas DXR accelerates kobs with little change in k-1.
      The antithetical behavior of MTX and DXR at the RyR raises the possibility that
      MTX antagonizes the ability of DXR to activate the RyR when the drugs are present
      in combination. In consonance with this hypothesis, MTX inhibits DXR (60 microM)
      sensitized [3H]ryanodine-binding sites in a dose-dependent manner (IC50 = 8.4
      microM) and shifts the EC50 for DXR-activated [3H]ryanodine-binding without
      reducing the maximum occupancy attained at high DXR concentration, revealing the
      competitive nature of the interaction of DXR and MTX. MTX singly does not alter
      active Ca++ accumulation by SR but is shown to fully inhibit DXR-induced Ca++
      release. The results suggest that MTX antagonizes DXR-activated RyR by binding to
      mutually exclusive sites and may provide a rational basis for combination therapy
      aimed at extending the current dose limits of DXR.

PMID- 8138935
TI  - The heroin metabolite, 6-monoacetylmorphine, activates delta opioid receptors to
      produce antinociception in Swiss-Webster mice.
AB  - Heroin activates delta receptors, whereas morphine activates mu receptors, in the
      brain of Swiss-Webster mice, to produce antinociception. The present study
      determined the type of opioid receptor activated by 6-monoacetylmorphine (MAM), a
      metabolite of heroin. Intracerebroventricular MAM-induced inhibition of the tail
      flick response was reduced by coadministration of naltrindole (a delta opioid
      receptor antagonist), suggesting that i.c.v. MAM, like i.c.v. heroin, acted on
      delta receptors. This delta receptor-mediated response was not affected by
      intrathecal (i.t.) administration of yohimbine and methysergide. Thus, the
      descending noradrenergic and serotonergic neuronal pathways, which are activated
      by i.c.v. morphine, were not involved in MAM antinociception. In the spinal cord,
      coadministration of naltrindole with MAM, i.t., decreased antinociception
      suggesting that MAM acted on spinal delta receptors. This finding is in contrast
      to i.t. heroin which acts on mu receptors in the spinal cord. These receptor
      selectivities were also demonstrated for systemically administered MAM and
      heroin. Thus, i.c.v. naltrindole inhibited both MAM- and heroin-induced
      antinociception, but i.t. naltrindole only inhibited the MAM response. The
      following results in ICR mice contrast with those above. Antinociception induced
      by i.c.v. MAM was decreased by coadministration of naloxone, but not naltrindole,
      suggesting that MAM, like morphine and heroin, acted on supraspinal mu receptors.
      Also, this MAM response was inhibited by i.t. administration of methysergide
      which is consistent with supraspinal mu receptor activation. Furthermore, i.t.
      MAM acted on spinal mu receptors because i.t. administration of naloxone, but not
      naltrindole, produced inhibition. In conclusion, the ability to ascribe delta
      receptor selectivity to the action of heroin and MAM in Swiss-Webster mice served
      to reinforce the concept that heroin and MAM act primarily on their own and not
      through formation of morphine. Further elucidation of the difference in heroin
      and MAM receptor selectivities between Swiss-Webster and ICR mice might
      contribute to a better understanding of opioid receptor mechanisms.

PMID- 8138936
TI  - Comparison of effects of dihydropyridine calcium antagonists on left ventricular
      systolic and diastolic performance.
AB  - We compared the effects of three dihydropyridine calcium antagonists (felodipine,
      nifedipine and amlodipine) on left ventricular (LV) contractile performance and
      diastolic filling dynamics in eight conscious animals. After administering
      metoprolol and atropine, felodipine (25 nmol/kg i.v.) produced significant
      decreases in LV end-systolic pressure (PES) (109 +/- 15 vs. 88 +/- 12 mmHg, P <
      .05) and arterial elastance (Ea) (12.6 +/- 4.5 vs. 8.5 +/- 3.4 mmHg/ml, P < .05),
      whereas the heart rate was unchanged. Felodipine increased the slopes of the end
      systolic P-V relation (7.4 +/- 0.9 vs. 9.9 +/- 1.0 mmHg/ml, P < .05), the
      dP/dtmax-end diastolic volume (VED) relation (68.1 +/- 11.2 vs. 94.9 +/- 14.3
      mmHg/sec/ml, P < .05), and the stroke work (SW)-VED relation (72.1 +/- 3.1 vs.
      82.8 +/- 5.2 mmHg, P < .05), and shifted all three relations to the left,
      indicating enhanced contractile performance. In contrast, at doses that produced
      equivalent reductions of PES, nifedipine (375 nmol/kg i.v.) and amlodipine (780
      nmol/kg i.v.), significantly decreased the slopes of the end-systolic P-V
      relation, the dP/dtmax-VED relation and the SW-VED relation and shifted all three
      relations to the right, indicating depressed LV contractile performance.
      Felodipine decreased the time constant (T) of LV relaxation (32.2 +/- 5.2 to 28.8
      +/- 5.2 msec, P < .05) and increased the maximum rate of early diastolic LV
      filling (dV/dtmax) (167 +/- 22 to 207 +/- 26 ml/sec, P < .05). Amlodipine had the
      opposite effect, slowing T (31.0 +/- 4.9 to 33.9 +/- 5.4 msec, P < .05) and
      decreasing dV/dtmax (173 +/- 39 to 154 +/- 30 ml/sec, P < .05), whereas
      nifedipine had no significant effects on T, PGmax or dV/dtmax. Thus, we conclude
      that in conscious dogs after autonomic blockade, at dosages that produced
      equivalent arterial vasodilation, felodipine augmented, whereas amlodipine
      depressed, LV contractile performance, LV relaxation and early LV filling.
      Nifedipine decreased LV contractile performance but had no significant effect on
      LV relaxation and early LV filling.

PMID- 8138937
TI  - Different metabolism of norepinephrine and epinephrine by catechol-O
      methyltransferase and monoamine oxidase in rats.
AB  - Normetanephrine (NMN) and metanephrine (MN), are the O-methylated metabolites of
      norepinephrine (NE) and epinephrine (E), whereas dihydroxyphenylglycol (DHPG) is
      the deaminated metabolite of both NE and E. This study compared production of
      NMN, MN and DHPG during tracer and high-dose infusions of Ne and E in rats, with
      and without inhibition of catechol-O-methyltransferase (COMT) or the A and B
      forms of monoamine oxidase (MAO). Animals also received infusions of NMN and MN
      to compare plasma clearances and spillovers of NMN and MN with and without MAO
      inhibition. Inhibition of COMT increased plasma DHPG and decreased plasma NMN and
      MN, whereas inhibition of MAO decreased plasma DHPG and increased plasma NMN and
      MN. The increase in NMN and MN after MAO inhibition reflected blocked deamination
      of NMN and MN by MAO-A, but not MAO-B. The A form of MAO was also largely
      responsible for deamination of NE. Infused E was deaminated to DHPG less
      efficiently than NE. High doses of infused E were O-methylated more efficiently
      than NE, whereas tracer doses were O-methylated similarly. After MAO inhibition
      NE was O-methylated more efficiently than E. Increased plasma NMN after MAO
      inhibition reflected the combined effects of a decrease in the plasma clearance
      of NMN and an increase in the spillover of NMN into plasma, whereas the smaller
      increase in plasma MN was due solely to a decrease in the plasma clearance of MN.
      Thus, E and MN are not deaminated at extraneuronal sites of O-methylation,
      whereas NE is both O-methylated and deaminated with proportionally more
      deaminated than O-methylated as the concentration of NE increases. The above
      results support the preference of NE over E for neuronal pathways of metabolism,
      but indicate considerably more complex differences in the metabolism of NE and E
      by extraneuronal O-methylation and deamination.

PMID- 8138938
TI  - Clentiazem given at reperfusion improves subendocardial reflow and reduces
      myocardial infarct size in the dog.
AB  - The postischemic cardioprotection by calcium antagonists and the interplay
      between neutrophils and regional myocardial blood flow were investigated further,
      using clentiazem, a new potent calcium channel blocker derived from diltiazem. A
      90-min occlusion of the interventricular coronary artery was followed by 6 hr of
      reperfusion in anesthetized dogs. One group was given clentiazem: 100
      micrograms/kg at 5 min before reperfusion followed by a perfusion of 1
      microgram/kg/min until sacrifice; controls received saline. Infarct size (% of
      area at risk) estimated with triphenyltetrazolium staining and by histology was
      reduced by nearly 50% (P < .05) in treated (16.6 +/- 3.0%), as compared to
      control (31.6 +/- 6.3%) dogs. Regional and collateral myocardial flows estimated
      with radioactive microspheres were similar between groups before and during
      occlusion. However, after an initial recovery to preocclusion values at 30-min
      reperfusion in both groups, flow declined to 50% normal (P < .05) in control
      animals after 3 and 6 hr in midwall and subendocardium, but the change was
      remarkably attenuated (P < .05) in subendocardium of clentiazem-treated dogs.
      Also, neutrophil accumulation at the epicardial side of the infarct, at the edge
      of salvaged myocardium, and estimated by tissue myeloperoxidase measurement, was
      reduced by 50% in treated dogs (clentiazem: 17.2 +/- 2.8; controls: 32.3 +/- 2.7
      x 10(6) neutrophils/g). We conclude that administration of clentiazem at
      reperfusion reduces infarct size by interfering with both neutrophil accumulation
      and development of subendocardial no reflow in reperfused myocardium.

PMID- 8138939
TI  - Dacarbazine toxicity in murine liver cells: a model of hepatic endothelial injury
      and glutathione defense.
AB  - The pathophysiology of hepatic veno-occlusive disease is poorly understood. These
      studies were undertaken to determine the initial cellular target and the role of
      glutathione detoxification of dacarbazine, a toxin implicated in hepatic veno
      occlusive disease. Sinusoidal endothelial cells (SECs) and hepatocytes were
      isolated and plated in culture dishes. Dacarbazine (5-(3,3-dimethyl-triazeno)
      imidazole-4-carboxamide), 3 and 6 mM, was toxic to SECs but not to hepatocytes.
      Onset of toxicity occurred between 11 and 12 hr as determined by serial MTT
      assays and ethidium homodimer dye exclusion. Glutathione detoxification of
      dacarbazine in SECs was suggested by: (1) depletion of glutathione before onset
      of toxicity; (2) exacerbation of toxicity by buthionine sulfoximine (BSO)
      depletion of glutathione; and (3) protection by exogenous glutathione. Protection
      by exogenous glutathione may be by uptake of intact tripeptide rather than by
      extracellular hydrolysis: neither acivicin (inhibitor of gamma
      glutamyltranspeptidase) nor BSO (inhibitor of gamma-glutamylcysteine synthetase)
      blocked the protective effect, and glutathione disulfide did not protect. The
      relative resistance to dacarbazine toxicity seen in hepatocytes is not due to
      more efficient GSH detoxification, because toxicity was not unmasked in
      hepatocytes cultures in medium lacking sulfur amino acid precursors of GSH. In
      conclusion, glutathione status may play an important role in the susceptibility
      to toxicity. Furthermore, the findings suggest that the SEC is the initial in
      vivo target of dacarbazine due to a relatively higher level of metabolic
      activation that more readily overcomes the available detoxification.

PMID- 8138940
TI  - Endogenous cannabinoid receptor binding activity released from rat brain slices
      by depolarization.
AB  - As previously reported by this laboratory, an endogenous factor capable of
      inhibiting the specific binding of the radiolabeled cannabinoid agonist [3H]CP
      55940 to its receptor can be released from nerve terminals in response to an
      influx of Ca++ induced by an ionophore (Evans et al., 1992). In the present
      report, we provide evidence that the endogenous ligand for the cannabinoid
      receptor can be released in response to a depolarizing stimulus (75 mM K+) in the
      presence of extracellular Ca++. K(+)-evoked release was not observed in the
      absence of extra-cellular Ca++ and was reduced by the specific calcium channel
      blockers verapamil and omega-conotoxin. The efflux of cannabinoid receptor
      binding activity is greatest within 2 min of stimulation with the Ca++ ionophore
      A23187. Within this period of time, the cannabinoid receptor binding activity was
      enhanced by the presence of a cocktail of peptidase inhibitors. Examination of
      the contribution of individual inhibitors for enhancing high K(+)-released
      material revealed a selectivity for captopril and thiorphan. The specificity of
      the released factor for the cannabinoid receptor was corroborated by its ability
      to compete with the aminoalkylindole radioligand [3H]WIN-55212 for binding to
      this receptor. Fractions from a semi-purified sample of the effluent demonstrated
      binding to the cannabinoid receptor and behaved as agonists in that these
      fractions could inhibit adenylate cyclase activity in neuroblastoma membrane
      preparations.

PMID- 8138941
TI  - Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor
      antidepressants, and by quinidine and ketoconazole: a model system to predict
      drug interactions in vivo.
AB  - Biotransformation of the tricyclic antidepressant desipramine (DMI) to its
      metabolite 2-hydroxy-desipramine (2-OH-DMI) was studied in vitro using microsomal
      preparations from human, monkey, mouse and rat liver. In all species 2-OH-DMI was
      the principal identified metabolite. Mean (+/- S.E.) reaction parameters in six
      human liver samples were: Vmax, 0.11 +/- .02 nmol/ml/min/mg protein; Km, 16.1 +/-
      4.2 microM. Quinidine was a highly potent inhibitor of 2-OH-DMI formation (mean
      Ki = 0.053 microM), consistent with the presumed role of Cytochrome P450-2D6 in
      mediating this reaction. Ketoconazole was a much less potent inhibitor (mean Ki =
      10.3 microM). Two serotonin-specific reuptake inhibitor (SSRI) antidepressants,
      and their respective metabolites, were evaluated as potential inhibitors of 2-OH
      DMI formation. Fluoxetine (FLU) and norfluoxetine (NOR) were the most potent
      inhibitors (mean Ki values: 3.0 and 3.5 microM, respectively). Sertraline (SERT)
      and its metabolite desmethylsertraline (DES) also inhibited the reaction (mean
      Ki: 22.7 and 16.0 microM), but were significantly less potent than FLU or NOR.
      Values of Ki and Km measured in vitro were used to generate a theoretical
      prediction of the degree of clearance inhibition in vivo at any given
      concentration of substrate and inhibitor. The model was applied to a clinical
      study in which DMI clearance in humans was impaired by coadministration of FLU
      (yielding FLU and NOR in plasma) or by SERT (yielding SERT and DES in plasma).
      Use of plasma SSRI concentrations in the predictive model underestimated the
      actual impairment of DMI clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138942
TI  - The effect of delta-9-tetrahydrocannabinol on arachidonic acid metabolism in
      human peripheral blood mononuclear cells.
AB  - Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of
      marijuana, is known to inhibit a variety of immune functions. However, the
      mechanisms of action of THC-induced immunosuppression are unclear. Because THC is
      known to affect arachidonic acid metabolism in non-lymphoid cells and because
      arachidonic acid metabolites are important regulators of the immune response, a
      detailed examination of the effects of THC on arachidonic acid metabolism in
      human peripheral blood mononuclear cells (PBMC) was performed. THC increased the
      amount of label released from PBMC prelabeled with [3H]-arachidonic acid. Further
      studies were performed using RP-HPLC to determine whether the increase in label
      release from cell membranes was due to the release of free [3H]-arachidonic acid
      or metabolites. Our results indicated that THC increases the production of the
      eicosanoid 12-HETE from PBMC. To determine whether other metabolites, such as the
      leukotrienes, were also affected by THC, leukotriene B4 (LTB4) was measured by
      enzyme immunoassay. THC was shown to increase markedly the production of LTB4
      from PBMC stimulated with the calcium ionophore A23187. These results indicate
      that THC alters arachidonic acid metabolism in lymphocytes by increasing the
      production of lipoxygenase products.

PMID- 8138943
TI  - Excitation of noradrenergic cell firing by 5-hydroxytryptamine1A agonists
      correlates with dopamine antagonist properties.
AB  - The 5-HT1A receptor agonists buspirone, 8-hydroxy-N,N-dipropyl-2-aminotetralin,
      gepirone and ipsapirone were evaluated for their receptor binding profiles and
      their effects on firing rates of 5-HT, dopamine (DA) and noradrenaline (NA)
      neurons in the dorsal raphe, substantia nigra pars compacta and the locus
      ceruleus, respectively. All agents bound to 5-HT1A receptors with high
      affinities. All agents also bound to dopamine D2 receptors but, with the
      exception of buspirone, affinities were usually much lower than for 5-HT1A
      receptors. All agents depressed 5-HT neurons, with 8-hydroxy-N,N-dipropyl-2
      aminotetralin having a potency about 8 to 12 times those for the other three. All
      agents also antagonized the inhibition of DA neurons by amphetamine, an index of
      DA antagonist properties. Buspirone reversed amphetamine's effects with doses
      similar to those for depressing 5-HT neurons, but the remaining three required
      much higher doses to affect DA neuron function. All four 5-HT1A agonists excited
      NA neurons. In each case, doses required for excitation of NA cells were similar
      to those reversing amphetamine's effects on DA cells, but not to those for
      depressing 5-HT cells. Haloperidol also stimulated NA cells. It is concluded that
      excitation of NA neurons by 5-HT1A agonists may be due to interactions with
      dopaminergic, rather than serotonergic, receptors.

PMID- 8138944
TI  - Uptake and phosphorylation of thiamine in rat kidney cortical slices. I. Effect
      of ethanol.
AB  - Processes involved in the disposition of thiamine within the kidney were studied
      in rat kidney slices. Uptake of [14C]thiamine and its metabolism to [14C]thiamine
      phosphate were measured with and without the presence of ethanol. Whereas slice
      to medium ratios of 3.41 +/- 0.11 indicated uphill movement of [14C]thiamine,
      metabolism to [14C]thiamine phosphate provided a metabolic sink for movement of
      thiamine into the cell. Accumulation was saturable and associated, in part, with
      the formation of thiamine phosphate. Ethanol, at 25 mM, a concentration
      compatible with alcohol abuse, significantly (P < .001) decreased the maximal
      accumulation of [14C]thiamine from 210 +/- 12.7 to 115 +/- 4.2 nmol/g and the
      production of thiamine phosphate from 0.44 to 0.041 nmol/g. These data indicate a
      facilitated uptake of thiamine and a conversion to thiamine phosphate by the
      kidney. The effect of ethanol to decrease thiamine accumulation in kidney tissue
      is suggested to be at the phosphorylating step.

PMID- 8138945
TI  - Uptake and phosphorylation of thiamine in rabbit primary proximal tubule cells
      and Madin Darby canine kidney cells. II. Effect of ethanol.
AB  - Uptake of [14C]thiamine was studied in renal primary proximal tubule cells and in
      Madin Darby Canine Kidney cells in culture. Findings were compared with data for
      the accumulation of [14C]thiamine and its phosphorylation in renal cortical
      slices. There was a saturable component for thiamine uptake in all cell types.
      When normalized for milligrams of protein, renal cortical slices accumulated 82%
      less 14C than renal primary proximal tubule cells and 51% less than distal tubule
      cells. Maximal [14C]thiamine levels accumulated by the saturable component was
      1.33 nmol/g in slices and 7.02 nmol/g in proximal tubule cells. Ethanol, at 25
      mM, inhibited thiamine uptake and phosphorylation in the cell cultures similar to
      its effect in the kidney tissue.

PMID- 8138946
TI  - Contraction of the guinea pig isolated, perfused trachea to purine and pyrimidine
      agonists.
AB  - Unlike methacholine and histamine, ATP and uridine 5'-triphosphate (UTP) are more
      potent contractile agonists when they are applied to the mucosal (intraluminal,
      IL) surface of the guinea pig perfused trachea than when they are applied to the
      serosal (extraluminal, EL) surface. The relative contractile activities of a
      series of purine and pyrimidine compounds were assessed. The order of EL activity
      was: [2-methythio ATP (2 MeSATP) = adenosine 5'-diphosphate (ADP)] > [adenosine
      5'-O-(2-thiodiphosphate) (ADP beta S) = ATP = adenosine 5'-O-(3-thiotriphosphate)
      (ATP gamma S)] > [(beta, gamma-imido ATP) (APPNP) = alpha, beta-methylene ATP
      (APCPP)] > [UTP = uridine 5'-diphosphate (UDP) = inosine 5'-triphosphate (ITP)] >
      [xanthosine 5'-triphosphate (XTP) beta, gamma-methylene ATP (APPCP)]. EL
      adenosine, adenosine 5'-monophosphate, uridine 5'-monophosphate and uridine were
      weak or inactive. The EL order of activity, therefore, shares some
      characteristics of P2Y receptors. The order of IL activity was: (ATP = UTP = ITP)
      > (ATP gamma S = ADP = APPNP = 2 MeSATP) > (UDP = ADP beta S = XTP) > APCPP; the
      other compounds were weak or inactive. The IL order of activity, therefore,
      resembled that for P2U or "nucleotide receptors." ATP, APPNP, UTP, UDP, ITP and
      XTP were more active when added to the IL than after administration to the EL
      bath; the remaining compounds were similarly active EL and IL, or were more
      active EL than IL. Greater IL than EL activity of agonists was a property
      associated with preference for P2U-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138947
TI  - Adenosine-induced bronchoconstriction and contraction of airway smooth muscle
      from allergic rabbits with late-phase airway obstruction: evidence for an
      inducible adenosine A1 receptor.
AB  - Recently, there has been an increasing interest in adenosine as a potential
      mediator of allergic asthma. In the present study, we used the allergic rabbit
      model developed in our laboratory to study the airway responses to adenosine and
      receptor binding in allergic lung vs. normal. Neonatal, pathogen-free rabbit
      litter mates were injected intraperitoneally within 24 hr of birth with ragweed
      pollen extract (1 mg/ml) to produce preferentially allergen-specific
      immunoglobulin E. Immunization produced bronchial airway hyperresponsiveness.
      Aerosolized adenosine (0.156-10 mg/ml) caused a dose-dependent
      bronchoconstriction (PC50 adenosine = 1.64 +/- 0.84 mg/ml). 9-Chloro-2-(2
      furyl)[1,2,4]triazole[1,5- c]quinazolin-5-amine (CGS-15943), a nonxanthine
      adenosine receptor antagonist, significantly inhibited the adenosine-induced
      airway obstruction in term of dynamic compliance (P < .05). Adenosine also
      increased the lung resistance in a dose-dependent manner which was significantly
      inhibited by CGS-15943 (P < .05). Nonimmunized, pathogen-free, age-matched
      rabbits (control) did not respond to adenosine at these same concentrations.
      Adenosine also produced a concentration-dependent (10(-9)-10(-4) M) contraction
      of isolated tracheal and bronchial airway rings in vitro from allergic rabbits
      but had no detectable effect on normal rabbit airway smooth muscle. Peripheral
      airway smooth muscles (secondary and tertiary) were more responsive to adenosine
      than central (tracheal) airways. The contraction produced by 10(-4) M adenosine
      in primary, secondary and tertiary airways was 90, 135 and 265% of the
      contraction produced by 50 mM KCl, respectively. CGS-15943 (10(-7) M)
      significantly inhibited the adenosine-induced contraction (P < .05) shifting the
      dose-response curve to the right.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138948
TI  - Drug effects on response-duration differentiation. II: Selective effects of
      antidepressant drugs.
AB  - Preclinical assays used to screen for antidepressant activity have traditionally
      been limited in their ability to selectively detect antidepressants. In the
      present study, we assessed the effects of antidepressant and non-antidepressant
      drugs on response-duration differentiation responding as a potential screen for
      antidepressant activity. Under this schedule, rats were trained to hold a lever
      in the down position for a duration greater than 1 sec but not more than 1.3 sec.
      The effects of the monoamine oxidase inhibitor tranylcypromine, the tricyclics
      imipramine and amitriptyline, and the atypical antidepressants trazadone and
      bupropion, as well as haloperidol, chlorpromazine, scopolamine and diazepam were
      studied. The antidepressant drugs selectively produced increases in the mean
      response durations. The non-antidepressant drugs produced much shorter mean
      response durations, although diazepam and chlorpromazine also increased the
      proportion of response durations that were greater than 1.3 sec. The order of
      potency of the antidepressants for increasing mean response durations
      corresponded well with their clinical potencies, suggesting that response
      duration differentiation may be useful in screening for antidepressant activity.

PMID- 8138949
TI  - Characterization of iris sphincter smooth muscle endothelin receptor subtypes
      which are coupled to cyclic AMP formation and polyphosphoinositide hydrolysis.
AB  - In the mammalian iris sphincter smooth muscle, endothelins (ET) activate both
      adenylate cyclase and the polyphosphoinositide cascade, and the levels of cyclic
      AMP (cAMP) and inositol 1,4,5-trisphosphate (IP3) produced are species specific.
      Radioligand binding studies, using [125I]ET-1 and [125I]ET-3 and determination of
      changes in cAMP, IP3 and contraction due to the peptides revealed the existence
      of ETA and ETB receptor subtypes in this tissue. In rabbit sphincter, ETA
      receptors constitute about 80% of total ET receptor population and these are
      coupled to IP3 production and contraction. In bovine sphincter, ETB receptors
      constitute about 72% of the total ET receptors and these are coupled to cAMP
      formation. Thus, in rabbit sphincter: 1) ET-1 and ET-2, two potent ETA receptor
      agonists, induced IP3 production and contraction at a much higher rate than ET-3,
      a weak ETA agonist. The EC50 for contraction by ET-1, ET-2 and ET-3 were 40, 45
      and 300 nM, respectively. 2) Sarafotoxin-S6c (SRTX-c), a selective ETB receptor
      agonist, had no effect on IP3 and contraction in this tissue. 3) D-Asp-L-Pro-D
      Val-L-Leu-D-Trp (BQ-123), a selective ETA receptor antagonist, inhibited the
      above responses to ET. 4) ET and SRTX-c induced cAMP formation at a much lower
      rate than that of IP3 and contraction. In contrast, in the bovine sphincter: 1)
      ET and SRTX-c induced cAMP formation in a dose-dependent manner, the order of
      potency being SRTX-c > ET-3 congruent to ET-2 congruent to ET-1.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8138950
TI  - Phenol red is a thromboxane A2/prostaglandin H2 receptor antagonist in canine
      lingual arteries and human platelets.
AB  - Phenol red (PR) is used as a pH indicator in cell culture medium. We found that
      cell culture medium containing PR relaxed canine lingual arteries (LA) contracted
      by the thromboxane A2/prostaglandin endoperoxide (TPE) receptor agonist (15S)
      hydroxy-11-alpha-9-alpha- (epoxymethano)prosta-5Z,13E-dienoic acid (U46619). We
      tested the effect of PR and the TPE receptor antagonist ONO-3708 on U46619,
      prostaglandin F2 alpha (PGF2 alpha), phenylephrine (PE) and potassium chloride
      (KCl)-induced contraction of the LA and on human platelet aggregation to U46619,
      ADP, arachidonic acid (AA), A23187 and thrombin. U46619, PGF2 alpha, KCl and PE
      produced equal tension development of the LA. PR relaxed the LA contracted with
      U46619 and PGF2 alpha with IC50 concentrations of 18.3 +/- 10 and 37.3 +/- 8.8
      microM, respectively. ONO-3708 inhibited the contractions to U46619 and PGF2
      alpha with IC50 of 9.4 +/- 2.2 and 12.2 +/- 2.2 nM, respectively. However, PR
      (300 microM) and ONO-3708 (300 nM) did not affect contraction of the LA to KCl or
      PE. PR inhibited human platelet aggregation, in vitro, to AA and U46619 and
      second wave aggregation to ADP but did not affect thrombin or first wave ADP
      mediated platelet aggregation. PR inhibited U46619 and AA-induced changes in
      cyclic AMP and Fura-2 calcium transients in platelets and LA. However, PR did not
      affect the activation of cyclic AMP or intracellular calcium ion in platelets or
      calcium influx and the release of intracellular calcium ion in canine LA produced
      by ryanodine, KCl and PE. The concentration of PR in many culture media is
      between 40 and 70 microM. The data support the conclusion that PR, in
      concentrations used as a pH indicator, is a selective antagonist of TPE
      receptors.

PMID- 8138951
TI  - Increased active stress generation of denervated rat intestinal smooth muscle:
      functional analysis of muscarinic receptor population.
AB  - The effects of denervation on the active stress production by the longitudinal
      muscle (LM) layer of rat jejunum were examined. Extrinsic and myenteric
      denervation of a segment of rat jejunum was accomplished by the serosal
      application of the cationic surfactant benzyldimethyltetradecylammonium chloride
      (BAC). Isolated muscle contraction experiments revealed that the LM of the
      jejunum taken from rats treated with BAC 15 days before developed significantly
      increased active stress in response to bethanechol and carbachol, but not in
      response to potassium chloride. No change in -log EC50 values of any of the
      agonists was observed in the denervated LM layer, although a significant increase
      in the slope of the carbachol and bethanechol concentration-response curves was
      observed in the denervated LM. Schild analysis of several muscarinic antagonists
      revealed a 3-fold increase in the apparent dissociation constant of the M2
      antagonist methoctramine in BAC-treated LM. These results suggest that the
      increased responsiveness of the denervated LM may originate in the muscarinic
      receptor population of the myocytes.

PMID- 8138952
TI  - Interactions between delta 9-tetrahydrocannabinol and kappa opioids in mice.
AB  - The selective kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) has
      been shown to modulate cannabinoid-induced antinociception by delta 9
      tetrahydrocannabinol (delta 9-THC). However, it is not known whether nor-BNI
      blocks other pharmacological effects of delta 9-THC or if this is a specific
      action of nor-BNI. Studies were conducted in which pretreatment with nor-BNI (2,
      10 and 20 micrograms i.t.) selectively blocked delta 9-THC-induced
      antinociception while not significantly affecting other commonly observed
      cannabinoid actions, which included hypothermia, hypoactivity and catalepsy.
      Chronic administration studies were performed to determine if cross tolerance
      could be established between delta 9-THC and the highly specific kappa opioid
      receptor agonists, U-50,488H and CI-977. The chronic delta 9-THC-treated groups
      were significantly tolerant, not only to i.t. delta 9-THC-induced antinociception
      in the tail-flick test, but also to i.t. U-50,488 and CI-977 compared with those
      treated chronically with vehicle. They were not cross tolerant to either DAMGO or
      DPDPE. Dose-response curves were generated for both delta 9-THC (i.t.) and CI-977
      (i.t.) in mice tolerant to delta 9-THC and CI-977. Parallel shifts to the right
      of the delta 9-THC dose-response curves were observed in animals tolerant to
      delta 9-THC and also in animals tolerant to CI-977. Animals tolerant to CI-977
      also demonstrated parallel shifts of the dose-response curves of both delta 9-THC
      and CI-977. This study demonstrated that cannabinoid actions can be distinguished
      from each other. The pharmacological separation of antinociception from the other
      cannabinoid-induced actions implies that it may have a mechanism distinct from
      other effects. In addition, this study indicates that delta 9-THC and the kappa
      opioid agonists may share a common mechanism of action in the production of
      antinociception and that a possible interaction exists between i.t. administered
      cannabinoid compounds and the kappa opioid receptor.

PMID- 8138953
TI  - Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1
      neurons: possible role of protein kinase C.
AB  - Ethanol has been reported to interact with numerous voltage- and ligand-gated ion
      channels in central mammalian neurons. In particular, the type A gamma
      aminobutyric acid (GABAA) receptor/chloride ionophore complex has received
      considerable attention as a cellular substrate for ethanol and other sedative
      hypnotic drugs. Direct electrophysiological evidence that ethanol modulates GABAA
      receptor function has been controversial. In this study, we investigated the
      effects of ethanol on the GABAA receptors that mediate fast inhibitory synaptic
      transmission in the rat hippocampus. Using the whole-cell patch-clamp recording
      technique in brain slices, we found that clinically relevant concentrations of
      ethanol (10-50 mM) potentiate pharmacologically isolated GABAA-mediated
      inhibitory postsynaptic currents (IPSCs) recorded from rat hippocampal CA1
      neurons. In addition, we demonstrate that ethanol- but not diazepam-mediated
      enhancement of GABAA IPSCs requires intracellular ATP and can be blocked by Ro-31
      8220 or PKC19-31, specific inhibitors of protein kinase C. Furthermore, the
      active phorbol ester 4-beta-PDBu but not its inactive analog also interferes with
      ethanol enhancement of GABAA IPSCs. These results demonstrate that ethanol
      potentiation of pharmacologically isolated GABAA IPSCs can be modulated by
      protein kinase C.

PMID- 8138954
TI  - Rapid protein synthesis and turnover is involved in interleukin-1-induced
      relaxation of the rabbit isolated mesenteric artery. Analysis of the arachidonate
      cascade.
AB  - The rabbit isolated superior mesenteric artery, when precontracted with
      phenylephrine, relaxes in a sustained manner in less than 30 min when exposed to
      recombinant interleukin-1 (IL-1), and this is a prostaglandin (PG)-dependent,
      endothelium- and 5-lipoxygenase-independent process. We have studied the
      dependency of IL-1-induced relaxation on protein synthesis and trafficking using
      isolated rings of rabbit mesenteric arteries. Three chemically unrelated protein
      synthesis inhibitors (PSIs) (cycloheximide, anisomycin and puromycin) completely
      prevented the response to IL-1. Moreover, the PSIs reversed IL-1-induced
      relaxations within 15 to 30 min of application. The amplitude and/or the duration
      of the relaxation induced by arachidonic acid and iloprost (a PGI2 mimetic) were
      partially inhibited by cycloheximide treatment, but not those induced by
      nitroglycerin or by cromakalim. However, tissues initially relaxed by IL-1 and
      then recontracted by a PSI are still able to relax when challenged with either
      arachidonic acid or iloprost, suggesting that cyclooxygenase is not depleted and
      that the responsiveness to PGs is intact under these conditions. Manoalide,
      thioether amide glycerophosphocholine (type II phospholipase A2 inhibitors) or
      brefeldin A (an inhibitor of intracellular protein trafficking) did not inhibit
      IL-1-induced relaxation. The data suggest the involvement of newly synthesized
      protein(s) with a very rapid turnover in the vascular response to IL-1. PSIs
      probably act at several levels to inhibit the relaxant response to IL-1, but
      depletion of tissue cyclooxygenase does not appear to be the limiting mechanism
      for the PSI effect on IL-1-induced relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138955
TI  - Influence of gender on vascular reactivity in the rat.
AB  - Tail artery ring segments and the isolated perfused mesenteric vascular bed from
      male, female metestrus and female proestrus Fisher 344 rats were used to study
      the influence of estrous cycle or gender on vascular reactivity. Vasodilator
      effects of nicotine on mesenteric vasculature and tail artery ring segments were
      not significantly different among the three groups. In the presence of
      guanethidine and methoxamine, transmural nerve stimulation of capsaicin-sensitive
      sensory nerves caused essentially the same level of frequency-dependent
      vasodilation in isolated perfused mesenteric vasculature in all three groups.
      Vasodilator responses to acetylcholine were not different with estrous cycle or
      gender. In tail artery ring segments, stage of estrous cycle or gender did not
      affect sensitivity to norepinephrine. Sensitivity to adrenergic nerve stimulation
      was significantly greater in male compared to female rats, but was not affected
      by estrous cycle stage. These data suggest that in the perfused mesentery
      vasodilator responsiveness to capsaicin-sensitive sensory nerve stimulation
      caused by either nicotine or transmural nerve stimulation is unaffected by gender
      or the estrous cycle, and endothelial function is also not influenced.
      Sensitivity to norepinephrine is also not affected, whereas sensitivity to
      adrenergic nerve stimulation is greater in males compared to females. Thus
      estrous cycle did not affect vascular responsiveness, but there were gender
      related differences.

PMID- 8138956
TI  - Central pre- and postsynaptic 5-HT1A receptors in rats treated chronically with a
      novel antidepressant, cericlamine.
AB  - Biochemical and electrophysiological approaches were used to assess the possible
      changes in 5-hydroxytryptamine (serotonin) 5-HT1A receptors in the rat brain
      after a long-term treatment with cericlamine [2-(3,4-dichlorobenzyl)-2
      dimethylamino-1-propanol], a novel serotonin reuptake inhibitor with
      antidepressant properties. Possible changes in other serotonin receptor binding
      sites (5-HT2A, 5-HT2C and 5-HT3) were also investigated after this treatment.
      Cericlamine was injected for 2 weeks at a dose (16 mg/kg i.p., twice daily) that
      ensured complete prevention of 4-methyl-alpha-ethyl-meta-tyramine-induced
      depletion of brain serotonin. In vitro binding and quantitative autoradiographic
      studies showed that neither 5-HT1A, 5-HT2A, 5-HT2C nor 5-HT3 receptor binding
      sites in various brain areas were affected by the 14-day treatment with
      cericlamine. Although forskolin-stimulated adenylate cyclase activity was
      significantly increased in hippocampal homogenates from cericlamine-treated rats,
      the reduction in this enzymatic activity due to 5-HT1A receptor stimulation by 8
      hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was unchanged in these animals
      as compared with controls. In contrast, in vitro and in vivo electrophysiological
      recordings of serotoninergic neurons in the dorsal raphe nucleus revealed a
      clearcut functional desensitization of somatodendritic 5-HT1A autoreceptors. Thus
      the potency of 8-OH-DPAT and ipsapirone to depress the firing rate of these
      neurons in brain stem slices was significantly reduced after the 2-week treatment
      with cericlamine. In vivo, the potency of an injection of cericlamine to inhibit
      the discharge of serotoninergic neurons was also markedly less in rats that had
      been pretreated for 2 weeks with this drug as compared with controls. However,
      the inhibitory effects of systemically injected 8-OH-DPAT and ipsapirone on the
      electrical activity of serotoninergic neurons were as pronounced in cericlamine
      treated rats as in controls. In addition, the reduction in serotonin synthesis
      due to an acute treatment with 8-OH-DPAT (0.1 or 0.3 mg/kg s.c.) was not
      significantly different in both groups of rats. These data support the idea that
      postsynaptic (in the hippocampus) and somatodendritic (in the dorsal raphe
      nucleus) 5-HT1A receptors are differently regulated in the rat brain, because
      only the latter receptors desensitized after a long-term blockade of serotonin
      reuptake by cericlamine. They also suggest that the inhibitory influence of
      systemically administered direct 5-HT1A agonists such as 8-OH-DPAT and ipsapirone
      on the electrical and metabolic activity of serotoninergic neurons does not
      result solely from the stimulation of somatodendritic 5-HT1A autoreceptors.

PMID- 8138957
TI  - Effect of scopolamine on the efflux of dopamine and its metabolites after
      clozapine, haloperidol or thioridazine.
AB  - The extracellular concentrations of dopamine (DA) and its metabolites,
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum
      and the nucleus accumbens were measured in awake, freely-moving rats. Clozapine
      (20 mg/kg, i.p.) increased extracellular DA and HVA in both regions but increased
      DOPAC only in the striatum. Scopolamine (1 mg/kg), although it had no effect by
      itself in the striatum or nucleus accumbens, inhibited the ability of clozapine
      to increase extracellular DA, DOPAC and HVA concentrations in the striatum. The
      clozapine-induced increase in DA in the frontal cortex was not blocked by
      scopolamine. Haloperidol (1 mg/kg, i.p.) and thioridazine (10 mg/kg, i.p.) also
      increased extracellular DA, DOPAC and HVA in the striatum, but scopolamine
      pretreatment did not inhibit these increases. The results suggest that clozapine
      differs from haloperidol and thioridazine in that the effect of clozapine, but
      not that of the two neuroleptic drugs, to increase DA release in the striatum
      acutely depends on muscarinic receptor stimulation. These results suggest that
      clozapine, despite its strong muscarinic antagonist properties, does not produce
      full blockade of muscarinic receptors in vivo in the striatum. The interaction of
      clozapine with the cholinergic system in the striatum could be relevant to its
      lack of ability to produce extrapyramidal symptoms or tardive dyskinesia.

PMID- 8138958
TI  - Acute effects of pentazocine, naloxone and morphine in opioid-dependent
      volunteers.
AB  - The purpose of this study was to evaluate the agonist and antagonist properties
      of pentazocine, an opioid mixed agonist-antagonist analgesic, in relation to
      prototypic opioid agonist and antagonist drugs in opioid-dependent human
      subjects. Pentazocine (45 and 60 mg), naloxone (0.1 and 0.2 mg), morphine (20, 40
      and 60 mg) and saline placebo were administered intramuscularly to six male
      volunteers maintained on methadone (30 mg/24 hr p.o.), following a double-blind,
      randomized block order design. Drugs were administered 20 hr after the last dose
      of methadone. Subject-reported effects and physiological measures were collected
      before drug administration and during 4 hr postadministration. Morphine produced
      significant dose-related increases in subjective measures characteristic of mu
      agonist effects, decreased pupil diameter and was classified as an opioid
      agonist. Naloxone precipitated a dose-related opioid withdrawal syndrome which
      was measurable on several subject-rated measures, and significantly increased
      pupil diameter. Subjects consistently identified naloxone as an antagonist.
      Pentazocine precipitated a withdrawal syndrome, but the effects were not dose
      dependent, and produced symptoms of confusion and dysphoric changes that were not
      observed after naloxone administration. Pentazocine was classified as an
      antagonist by some individuals, and as alcohol or hallucinogen by others. The
      results of the present study indicate that pentazocine acts in humans as a
      partial mu agonist with a non-mu component of activity.

PMID- 8138959
TI  - The leukotriene B4 receptor agonist/antagonist activities of SC-45694 in human
      neutrophils.
AB  - SC-45694 (7-[4-(1-hydroxy-3Z-nonenyl)phenyl]-5S-hydroxy-6Z-hept enoic acid
      lithium salt), a representative of a new class of leukotriene B4 (LTB4) analogs
      that are conformationally restricted, was evaluated for effects on human
      neutrophil functions. SC-45694 inhibited [3H] LTB4 binding to the high-affinity
      receptors on human neutrophils with a KD value of 0.76 microM, but it was a very
      weak inhibitor of [3H]N-formyl-methionyl-leucyl-phenylalanine binding (KD > 83
      microM). SC-45694 stimulated neutrophil chemotaxis with half-maximal and maximal
      effects at 1 and 10 microM, respectively, and produced a maximal chemotactic
      response similar to that produced by LTB4. The chemotactic activity of SC-45694
      was blocked by the LTB4 receptor antagonists SC-41930 and LY-255283. At
      concentrations that showed agonist activity for neutrophil chemotactic response,
      SC-45694 showed no agonist activity for degranulation, antagonized LTB4-induced
      degranulation and inhibited [3H] LTB4 binding to low-affinity receptors. SC-45694
      inhibited LTB4-induced maximal degranulation with an IC50 value of 0.3 microM,
      but it did not inhibit N-formyl-methionyl-leucyl-phenylalanine-induced
      degranulation. The inhibition by SC-45694 of LTB4-induced degranulation was time
      dependent, noncompetitive and reversible. Thus SC-45694 exhibited a specific,
      full LTB4 agonist activity for chemotaxis and an antagonist activity against LTB4
      induced degranulation. These properties suggest that members of the new class of
      LTB4 analogs, such as SC-45694, may be useful in further characterizing distinct
      LTB4 receptor subtypes that mediate these two neutrophil functions.

PMID- 8138960
TI  - The in vitro pharmacology of SC-51146: a potent antagonist of leukotriene B4
      receptors.
AB  - Previously, we reported that SC-41930 is a potent leukotriene B4 (LTB4) receptor
      antagonist. An analog of SC-41930, SC-51146, was evaluated as an antagonist of
      LTB4 receptors. SC-51146 was shown to bind to LTB4 high affinity binding sites on
      human neutrophils (PMN) with a dissociation constant (KD) value of 1.5 +/- 0.1
      nM, compared to 19 +/- 1.3 nM for SC-41930. PMN chemotaxis studies and Scatchard
      analyses of [3H]LTB4 binding in PMN membranes indicated that SC-51146 acted as a
      competitive antagonist. The IC50 value of SC-51146 for the inhibition of PMN
      chemotaxis induced by 30 nM LTB4 was 38 +/- 12 nM. SC-51146 inhibited PMN
      degranulation induced by 50 nM LTB4 with an IC50 value of 29 +/- 7 nM. The
      antagonism by SC-51146 of LTB4-induced PMN degranulation appeared to be
      noncompetitive. The specificity of SC-51146 for LTB4 receptors vs. fMLP receptors
      was improved approximately 29 and 44 times over SC-41930. SC-51146 showed
      relatively weak inhibitory activity on the production of superoxide, LTB4 and/or
      prostaglandin E2 by human PMN or HL-60 cells. SC-51146 had little activity on ram
      seminal vesicle cyclooxygenase, and no activity on porcine pancreatic
      phospholipase A2. SC-51146 is a racemate comprised of the (+) enantiomer, SC
      53228, and the (-) enantiomer, SC-53229. Both stereoisomers exhibited
      pharmacological profiles similar to SC-51146 in these aforementioned in vitro
      systems. The highly potent and specific antagonistic action of SC-51146 on LTB4
      receptors should be particularly useful in elucidating the role of LTB4 in the
      pathogenesis of inflammatory diseases where excessive levels of LTB4 have been
      reported.

PMID- 8138961
TI  - Repeated administration of selective adenosine A1 and A2 receptor agonists in the
      spontaneously hypertensive rat: tolerance develops to A1-mediated hemodynamic
      effects.
AB  - We investigated the effects of the selective A1 adenosine receptor agonist 2
      chloro-N6-cyclopentyladenosine (CCPA), the selective A2 adenosine agonists 2
      hexynyl-5'-N-ethyl-carboxamidoadenosine(2-hexynyl-NECA) and 2-[p-(2-carboxyethyl)
      phenethylamino]-5'-N-ethylcarboxamidoadenosi ne (CGS 21680), and the nonselective
      adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) on systolic blood
      pressure (SBP), heart rate (HR) and receptor binding characteristics. The drugs
      were studied after acute and repeated i.p. administration in conscious,
      spontaneously hypertensive rats (SHRs). SBP and HR were recorded by the tail-cuff
      method. In acute studies the drugs induced a dose-dependent antihypertensive
      effect with the following order of potency: 2-hexynyl-NECA > NECA > CCPA = CGS
      21680. As expected, the A1 agonist CCPA induced a dose-dependent bradycardia,
      whereas the A2 agonists had minimal influence on HR, and the nonselective agonist
      NECA induced bradycardia only at the two highest doses. In chronic experiments,
      the compounds were administered twice daily at equihypotensive doses. 2-Hexynyl
      NECA, CGS 21680 and NECA maintained their antihypertensive effects throughout the
      experimental period. After 21 days, SBP levels were -32, -38 and -28% vs.
      baseline, respectively. HR was slightly affected. Conversely, tolerance developed
      to both hypotensive and bradycardic effects of CCPA: at day 21 SBP regained the
      pretreatment value (+2% vs. baseline), and HR also recovered (-14% vs. baseline).
      Binding studies were performed on cerebral tissues: no differences were observed
      between treated and control rats in number and affinity of either A1 and A2
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138962
TI  - Pharmacokinetics of Vipera aspis venom after experimental envenomation in
      rabbits.
AB  - Toxicokinetic studies of Vipera aspis venom were performed in rabbits after
      experimental envenomation. Venom proteins with a molecular weight greater than 6
      kDa (high-molecular weight proteins) and which reacted in enzyme-linked
      immunosorbent assay with specific antiviper venom Fab'2, were also responsible
      for the lethal potency and the capillary permeability increasing activity of the
      venom. Conversely, low-molecular weight proteins were not detected by enzyme
      linked immunosorbent assay and were pharmacologically inactive. The
      toxicokinetics of both classes of venom components were studied, using high
      molecular weight and low-molecular weight radiolabeled proteins as well as enzyme
      linked immunosorbent assay. After intravenous injection, Vipera aspis venom in
      plasma followed a biexponential decline with a distribution half-life of 0.7 hr
      and an elimination half-life of 12 hr. The distribution volume was 1.2 l.kg-1 and
      the systemic clearance was 84 ml.hr-1.kg-1. Venom levels in plasma after
      intramuscular injection of three doses (300, 500 and 700 micrograms/kg) of venom
      increased within the few hours after the venom administration to reach maximal
      values proportional to the injected doses. They subsequently followed a
      monoexponential decline, with an apparent terminal half-life of 32.5 hr.
      Absorption was a kinetically complex process, rapid during the first 24 hr and
      continued at a slower rate over the subsequent 72 hr. Bioavailability of venom
      was about 65%, regardless of the administered dose, and less than 5% of venom
      injected was excreted by the renal route.

PMID- 8138963
TI  - Interspecies differences in enantioselective mono-N-dealkylation of disopyramide
      by human and mouse liver microsomes.
AB  - The interspecies differences in the enantioselective metabolism of disopyramide
      (DP) were studied with human and mouse liver microsomes. Mono-N-dealkylation of
      both DP enantiomers was biphasic, suggesting an involvement of two enzymes in the
      metabolism in both species. The human data indicated that the metabolism of both
      DP enantiomers at the therapeutic concentrations (i.e., 5-14 microM) was mediated
      by the high-affinity components. The mean (+/- S.D.) affinity constant (Km) of
      the high-affinity component for S-(+)-DP (4.86 +/- 2.66 microM) was significantly
      (P < .05) lower than that for R-(-)-DP (24.61 +/- 17.52 microM), whereas no
      difference was observed between the maximum velocities (Vmax) for S-(+)- and R-(
      )-DP. The mean intrinsic clearance (CL(int)), defined as Vmax/Km, of the high
      affinity component for S-(+)-DP was significantly greater (P < .01) than that for
      R-(-)-DP, consistent with the reported in vivo pharmacokinetic data. In contrast,
      the CL(int) of the low-affinity component for R-(-)-DP was significantly (P <
      .01) greater than that for S-(+)-DP. Coincubation of DP enantiomers as a racemate
      showed mutual competitive inhibition. With mouse liver microsomes, a preferential
      metabolism of S-(+)-DP over R-(-)-DP was also observed only for the high-affinity
      components. Although the mean Vmax for the high-affinity component of mouse
      microsomes was about 6- to 8-fold greater than that of human's, the differences
      in Km were at most 2.5-fold. In addition, metabolic competition between the
      enantiomers also occurred with mouse microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138964
TI  - Anti-inflammatory effect of prostanoids in mouse and rat skin: evidence for a
      role of EP3-receptors.
AB  - The effects of prostaglandin E1 (PGE1) and certain PGE-analogs on edema formation
      were investigated in mouse and rat skin. In the mouse, intradermal administration
      of both zymosan-activated serum (ZAS) (5-50% per site) and platelet-activating
      factor (PAF) (0.1-5.0 nmol/site) caused dose-related increases in edema
      formation. PGE1 (0.003-3.0 nmol/site) caused a dose-related inhibition of the
      edema response to ZAS, whereas a dose of 0.3 nmol potentiated the edema response
      to PAF. Sulprostone, which is selective for EP1 and EP3 PGE-receptors, produced a
      potent inhibition of the edema responses to both ZAS (80%) and PAF (60%).
      Misoprostol, which is selective for both EP2- and EP3-receptors, inhibited the
      edema response to ZAS (> 40%) but had no effect on the response to PAF. Treatment
      of mice with the thromboxane A2-receptor antagonist GR32191B did not modify the
      anti-inflammatory activity of PGE1 or sulprostone. In the rat skin model, PGE1
      produced only potentiation of the responses to both ZAS and PAF. However,
      sulprostone displayed significant inhibitory effects on the edema responses to
      both stimuli (40-50%). From these data we propose that the anti-inflammatory
      activity of PGE1 and of the two analogs sulprostone and misoprostol may be
      mediated via activation of the contractile EP3-receptor. Differences in the
      responses to prostanoids from one species to another may reflect differences in
      the relative densities of receptor subtypes mediating opposite effects.

PMID- 8138965
TI  - Cocaine-induced cerebrovasospasm and its possible mechanism of action.
AB  - Experiments were designed to study the effects and mechanism of action of cocaine
      (COC) on cerebrovascular tissues. Acute exposure to COC (10(-9) to 5 x 10(-3) M)
      induced contractile responses in isolated canine basilar (BA) and middle cerebral
      arteries in a dose-dependent manner, but not in mesenteric arteries. The presence
      or absence of intact endothelium did not alter COC concentration-response curves.
      The sensitivity to COC was higher in BA (ED50 = 7.20 +/- 0.16 x 10(-5) M) than
      middle cerebral arteries (ED50 = 1.25 +/- 0.12 x 10(-4) M). Similar effects of
      COC were also noted in BA from piglets (ED50 = 0.99 +/- 0.25 x 10(-4) M) and
      sheep (ED50 = 1.34 +/- 0.31 x 10(-4) M). A variety of amine antagonists, an
      opiate antagonist and an N-MDA receptor antagonist failed to interfere with the
      COC-induced contractions. However, haloperidol, indomethacin, verapamil and
      excess [Mg++]0 (4.8 x 10(-3) M) as well as removal of [Ca++]0 completely
      prevented vasospasms induced by COC. Dopamine and COC resulted in very similar
      concentration-response curves on canine BA. COC stimulation failed to affect
      vascular release of thromboxane B2, prostaglandins or 6-Keto-prostaglandin F1
      alpha. Interestingly, 10(-7) M COC rapidly elevated intracellular free Ca++
      concentrations of cultured cerebral vascular muscle cells about 50% over initial
      resting levels. The data suggest that COC produces cerebrovasospasm, probably by
      a direct action on cerebral blood vessels via promoting Ca++ influx and/or
      intracellular Ca++ release in cerebral vascular muscle cells, which may be
      modulated by Mg++.

PMID- 8138966
TI  - Antihypertensive effects of a highly potent and long-acting angiotensin II
      subtype-1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1
      [[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV
      116), in various hypertensive rats.
AB  - The antihypertensive effects of (+-)-(cyclohexyloxycarbonyloxy)ethyl2-ethoxy-1
      [[2'-(1H- tetrazol-5- yl)biphenyl-4-yl]methyl]-1-H-benzimidazole-7-carboxylate
      (TCV-116), an angiotensin II (AII) subtype-1 receptor antagonist, were studied in
      various hypertensive and normotensive rats, using 2-n-butyl-4-chloro-5
      hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4- yl)methyl]-imidazole,
      potassium salt (losartan) as a reference compound. TCV-116 is a prodrug, which is
      converted in vivo to the active component, 2-ethoxy-1-[[2'-(1H-tetrazol-5
      yl)biphenyl-4-yl)]methyl]-1H- benzimidazole-7-carboxylic acid (CV-11974). In
      spontaneously hypertensive rats (SHR) p.o. TCV-116 (0.1 mg/kg) demonstrated a
      sustained antihypertensive effect that lasted for more than 10 hr and the dose
      that reduced the blood pressure by an average of 25 mm Hg for 24 hr (ED25), was
      0.68 mg/kg. Intravenous CV-11974 reduced the blood pressure with an ED25 of
      0.0027 mg/kg. Repeated p.o. administration of TCV-116 (1 mg/kg) to SHR once daily
      for 2 weeks reduced the blood pressure by 30 to 50 mm Hg over 24 hr without any
      heart rate changes. The antihypertensive effects of TCV-116 correlated well with
      the inhibition of angiotensin II-induced contractile responses of aortic strips
      prepared ex vivo after p.o. administration of TCV-116. Oral TCV-116 had a
      sustained antihypertensive effect with ED25 of 0.03 and 0.23 mg/kg in two-kidney,
      one-clip and one-kidney, one-clip hypertensive rats, respectively, and was much
      more potent in SHR and renal-hypertensive rats than losartan.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8138967
TI  - Effects of local anesthetics on experiential, physiologic and endocrine measures
      in healthy humans and on rat hypothalamic corticotropin-releasing hormone release
      in vitro: clinical and psychobiologic implications.
AB  - Local anesthetics, given i.v. to treat cardiac arrhythmias and for regional
      anesthesia, exert prominent central nervous system side effects, such as sensory
      distortions and mood changes. In experimental animals, these drugs activate
      limbic structures, such as the amygdala, that may coordinately regulate sensory
      processing, mood and pituitary hormone secretion during stress. Clinically
      relevant i.v. doses of the short-acting local anesthetic procaine were
      administered to 17 healthy volunteers and topographic electroencephalographic
      (EEG) spectra, stress-responsive neuroendocrine and cardiovascular parameters and
      sensory-cognitive and mood changes were examined. Because corticotropin-releasing
      hormone (CRH) mimics the behavioral and physiologic responses to stress and
      activates limbic structures in experimental animals, the effects of procaine and
      lidocaine on immunoreactive CRH release from rat hypothalami in vitro were also
      explored. Procaine administration produced a dose-related increase in fast (21-50
      Hz) EEG activity, a significant decrease in alpha EEG activity and dose-dependent
      increases in heart rate, systolic blood pressure and plasma adrenocorticotropic
      hormone, cortisol and prolactin secretion. Dose-dependent increases in sensory
      distortions involved virtually all modalities, particularly auditory, visual and
      somatosensory. Mood changes occurred in most subjects, including anxiety,
      euphoria and arousal. In vitro, procaine and lidocaine both produced significant
      dose-related increases in immunoreactive CRH release from rat hypothalami,
      maximal at 10(-6) M, that were blocked by carbamazepine, a limbic anticonvulsant
      used in the management of mood disorders. The electrophysiologic effects of
      procaine in these volunteers were analogous to local anesthetic effects in
      experimental animals and consistent with the activation of subcortical structures
      localized within the temporal lobe, such as the amygdala. The effects of procaine
      on stress-responsive neurohormones were similar to those of amygdala stimulation
      both in experimental animals and human subjects. The in vitro data suggested that
      procaine-induced pituitary-adrenal activation involves stimulation of
      hypothalamic CRH, although additional (e.g., limbic-hypothalamic) mechanisms may
      contribute in vivo. These data were compatible with a direct action of local
      anesthetics on limbic structures that might account for many of the central
      effects seen with the systemic use of these agents in clinical practice.

PMID- 8138968
TI  - Cytochrome P450 2B enzyme induction defect after 2,2',4,4',5,5'
      hexachlorobiphenyl treatment in the fa/fa Zucker rat.
AB  - The present study describes the effects of 2,2',4,4',5,5'-hexachlorobiphenyl, a
      "phenobarbital-like" inducer of hepatic cytochrome P450, on the CYP2B1 and CYP2B2
      enzymes in the phenotypically obese fa/fa Zucker rat. The fa/fa Zucker rat
      demonstrated a markedly lower level of CYP2B1/2B2 enzyme induction, as indicated
      by reduced enzyme activity (testosterone 16 beta-hydroxylation and
      pentoxyresorufin O-dealkylation), protein concentration (Western blot), and mRNA
      (slot blot) than the lean Fa/? rodents after in vivo treatment with
      2,2',4,4',5,5'-hexachlorobiphenyl. A primary hepatocyte cell culture system was
      used to control for possible differences in the disposition of 2,2',4,4',5,5'
      hexachlorobiphenyl and hormonal dissimilarity between obese and lean Zucker rats.
      In agreement with the in vivo study, hepatocytes from fa/fa Zucker rats treated
      with 2,2',4,4',5,5'-hexachlorobiphenyl exhibited a poor induction response based
      on measurement of CYP2B1/2B2 mRNA. These data are similar to those reported
      earlier that demonstrate resistance of the CYP2B1/2B2 genes to the inductive
      effects of phenobarbital in fa/fa Zucker rats. Apparently a genetic defect in
      obese Zucker rats impairs the increase in CYP2B1/2B2 gene transcription after
      treatment with phenobarbital as well as 2,2',4,4',5,5'-hexachlorobiphenyl. This
      study provides evidence that phenobarbital and "phenobarbital-like" inducers
      share a common cellular element(s) in the induction process of the CYP2B1/2B2
      enzymes.

PMID- 8138969
TI  - Further studies of the role of hyperthermia in methamphetamine neurotoxicity.
AB  - The depletion of striatal dopamine (DA) that can occur after methamphetamine
      (METH) administration has been linked to METH-induced hyperthermia. The
      relationship between METH-induced hyperthermia, neurotoxicity (striatal DA
      depletions) and compounds that protect against METH neurotoxicity was further
      investigated in this study. Typically, rats exposed to METH die when their body
      temperatures exceed 41.3 degrees C but such hyperthermic rats can be saved by
      hypothermic intervention. Subsequently, rats saved by hypothermic intervention
      have greater depletion of striatal DA at an earlier time of onset (18 hr or less
      post-METH) than do METH-exposed rats that do not attain such high temperatures.
      Striatal damage was present 3 days post-METH in these hyperthermic rats, as
      assessed by silver degeneration of terminals and increases in the astrocytes that
      express glial fibrillary acidic protein immunoreactivity. By contrast,
      alterations in the number of [3H]dizoclipine (MK-801) binding sites in cortical
      or striatal membranes at 1, 3 or 14 days post-METH were not detected. The
      experiments showed that mean and maximal body temperature correlated well with
      striatal DA concentrations 3 days post-METH (r = -0.77, n = 58), which suggests a
      role for hyperthermia in METH neurotoxicity. However, hyperthermia (alone or with
      haloperidol present) induced by high ambient temperatures did not deplete
      striatal DA in the absence of METH. Haloperidol, diazepam and MK-801 all reduced
      METH-induced striatal DA depletion to a degree predicted by their inhibition of
      hyperthermia and increased ambient temperature abolished their neuroprotection.
      Although an interleukin-1 receptor antagonist reduced maximal body temperature
      enough to lower the lethality rate, it did not reduce the temperature
      sufficiently to block METH neurotoxicity. It was concluded that short- and long
      term decreases in striatal DA levels depend on the degree of hyperthermia
      produced during METH exposure but cannot be produced by hyperthermia alone. In
      addition, several agents that block DA depletions do so by inhibiting METH
      induced hyperthermia. Finally, the results suggested a role for interleukin-1 in
      the extreme hyperthermia and lethality produced by METH.

PMID- 8138970
TI  - Calcium channel blockers modify electrophysiological effects induced by lytic
      granules from cytotoxic T lymphocytes in guinea pig ventricular myocytes.
AB  - Damage to myocytes by infiltrating cytotoxic lymphocytes, containing lytic
      granules and the pore-forming protein, perforin, thereof, probably contribute to
      the immunological rejection of the transplanted heart, to autoimmune diseases and
      possibly to congestive heart failure associated with myocarditis. In the present
      study we investigated whether electrophysiological and morphological changes
      induced in guinea pig ventricular myocytes by lytic granules extracted from
      cytotoxic T lymphocytes, are modified by L-type Ca++ channel blockers. The
      organic blockers, verapamil (2 microM) and nisoldipine (500 microM) were unable
      to prevent or inhibit any of the deleterious effects of lytic granule on action
      potential and myocyte morphology, and the granule-induced increase in the
      membrane current measured at the end of 300-msec clamp pulse. In contrast, the
      inorganic blockers CoCl2 (3 mM) and NiCl2 (4 mM) provided considerable protection
      against the granule actions mentioned above, but an equally potent Ca++ blocker,
      CdCl2 (3 mM) was ineffective. The protective efficacy of CoCl2 (and probably that
      of NiCl2) was most likely due to its capacity to reduce or block the generation
      by lytic granules/perforin of large-conductance (approximately 1400 pS) channels
      responsible for inducing Ca++ overload and cell destruction. We consider these
      studies of importance because they direct further studies aimed at developing
      effective means for attenuating cytotoxic T lymphocyte-induced tissue damage, for
      example during transplant rejection or in autoimmune diseases.

PMID- 8138971
TI  - Protective effects of MCI-186 on cerebral ischemia: possible involvement of free
      radical scavenging and antioxidant actions.
AB  - The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3
      methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment
      with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic
      activity and prolonged survival time in global complete ischemia of rats; MCI-186
      (1 and 3 mg/kg i.v.) also mitigated dysfunction of the blood-brain barrier and
      energy failure in hemispheric embolization of rats. Postischemic treatment with
      MCI-186 (3 mg/kg i.v.) decreased cortical infarction in focal embolization of
      rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of salicylate
      (maximal inhibition, 40.2%), but at 100 microM it did not influence O2-
      generation. MCI-186 inhibited the formation of linoleic acid-conjugated dienes
      caused by OH. (IC50 = 32.0 microM). Also, concurrent administration of MCI-186 (3
      100 mg/kg i.v.) ameliorated hyperglycemia, hyperlipopeoxidemia and degranulation
      of beta-cells in alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186
      inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial
      homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented iron
      dependent peroxidative disintegration of mitochondrial membranes (IC50 = 39.0
      microM). These findings suggest that MCI-186 has potent anti-ischemic actions and
      that its mechanism may be closely associated with beneficial antioxidant
      activities.

PMID- 8138972
TI  - Patterns of messenger RNA expression for adrenergic receptor subtypes in the rat
      kidney.
AB  - The distribution of mRNA for the rat alpha-1 A/D, alpha-1B, alpha-2A/D (RG20),
      alpha-2B (RNG), alpha-2C (RG10), beta-1 and beta-2 adrenergic receptors were
      studied in the rat kidney using in situ hybridization. After hybridized sections
      were exposed to autoradiography film or dipped in photographic emulsion and
      counterstained with hematoxylin and eosin, specific and selective labeling
      patterns characteristic for each probe in the kidney were observed. Labeling with
      the probe to the alpha-1A/D receptor was only observed in vessels in the renal
      parenchyma and in the ureter. Alpha-1B receptor mRNA was demonstrated in the
      outer and inner stripe of the outer medulla, corresponding to segment S3 of
      proximal tubules and the thick ascending limb of loop of Henle. Alpha-2A/D
      receptor mRNA was distributed in the inner stripe of the outer medulla and in the
      inner medulla, corresponding to collecting tubules, and in the ureter. The
      strongest signal in the kidney was obtained with the alpha-2B receptor probe,
      showing labelling in the outer stripe of the outer medulla with tubular rays
      radiating into the cortex, coinciding with segment S3 of proximal tubules. Weak
      labeling obtained with the alpha-2C receptor probe was present in the renal
      medulla. Labeling obtained with the probe to the beta-1 receptor was seen in the
      entire cortex and to a lesser extent also in the outer medulla. In addition, beta
      1 receptor mRNA was shown in perirenal adipose tissue and in the ureter. Labeling
      obtained with the probe to the beta-2 receptor was demonstrated in the outer and
      inner stripe of the outer medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8138973
TI  - Localization of cannabinoid receptors and nonsaturable high-density cannabinoid
      binding sites in peripheral tissues of the rat: implications for receptor
      mediated immune modulation by cannabinoids.
AB  - [3H]CP-55,940, a high-affinity cannabinoid receptor ligand, was used for in vitro
      binding and autoradiography in peripheral tissues in the rat. Specific
      cannabinoid receptor binding was found to be restricted to components of the
      immune system, i.e., spleen, lymph nodes and Peyer's patches. Displacement
      studies showed that this binding is identical (similar Kd and structure-activity
      profile) to that in brain. Cannabinoid receptors in the immune system are
      confined to B lymphocyte-enriched areas, i.e., the marginal zone of the spleen,
      cortex of the lymph nodes and nodular corona of Peyer's patches. Specific binding
      is absent in T lymphocyte-enriched areas, such as the thymus and periarteriolar
      lymphatic sheaths of the spleen. Certain macrophage-enriched areas, i.e., liver
      and lung, lack specific binding. Thus, the single peripheral cell type that may
      contain cannabinoid receptors is the B lymphocyte. Numerous sites have dense
      binding that could not be displaced by excess unlabeled drug. These nonspecific
      sites were found in the liver, adrenal glands and sebaceous glands, which are
      high in fat content, and in the heart, pancreas, components of the male and
      female reproductive systems and the epithelium of the esophagus. Thus, the highly
      lipophilic nature of cannabinoids does not appear to be the sole determinant of
      nonspecific binding. The data suggest that cannabinoids may exert specific
      receptor-mediated actions on the immune system of rats. Perhaps, also at high
      concentrations, cannabinoids exert membrane effects at sites where they are
      sequestered nonspecifically.

PMID- 8138974
TI  - Developmental odontogenic cysts. An update.
AB  - This review paper reports recent advances in the subject of developmental
      odontogenic cysts, essentially those of the past decade, starting with reference
      to the new WHO classification (1). On keratocysts, the latest reported recurrence
      rates are assessed as are their mode of growth, immunocytochemistry, immunology,
      genetic studies, and work on specific keratocyst antigens. There is a critical
      account of the group of lesions which includes the gingival cyst of adults,
      lateral periodontal cyst, botryoid odontogenic cyst and glandular odontogenic
      cyst, and their possible relationship to one another. On dentigerous cysts,
      reference is made to the relationship between them and deciduous teeth, as well
      as to their immunocytochemistry and immunology. Recent work on the unicystic
      ameloblastomas, their classification and prognosis, is assessed, as is the
      calcifying odontogenic cyst and its relationship with solid odontogenic tumours.

PMID- 8138975
TI  - Paget's disease of bone: current concepts in pathogenesis and treatment.
AB  - Recent advances have been made in understanding the aetiology, diagnosis and
      treatment of Paget's disease of bone (osteitis deformans). The role of viruses in
      the pathogenesis of the disease has been extensively investigated, although no
      causative link has yet been demonstrated between infective agents and Paget's
      disease. Recent advances in the diagnosis of the disease have been made with
      increasing usage of radionucleotide imaging to determine the extent and
      distribution of the lesions. Treatment options have been extended with the
      emergence of the biphosphonates as potential main line therapeutic agents.

PMID- 8138976
TI  - Cellular kinetics and lectin distribution in hamster buccal carcinomas.
AB  - As part of an evaluation of the progression to malignancy, the cellular kinetics
      of DMBA-induced tumors in the buccal mucosa of hamsters were examined using 5
      bromodeoxyuridine (BrdU), peanut agglutinin (PNA), Ulex europaeus agglutinin I
      (UEA-I) and wheat germ agglutinin (WGA). BrdU-positive cells were localized in
      the basal layer in both normal and hyperplastic epithelium, whereas they were
      distributed from the basal to the prickle cell layer in squamous cell carcinoma
      (SCC). The extent of BrdU labeling increased as the tissues progressed towards
      malignancy. PNA and UEA-I showed binding only in the prickle cell layer of normal
      and hyperplastic epithelium, and WGA showed binding mainly in the prickle cell
      layer. However, in SCC, PNA and UEA-I showed no binding in the prickle cell layer
      and WGA binding was observed throughout the epithelium. A study of cellular
      kinetics using BrdU labeling and the lectin binding pattern may be useful in the
      evaluation of tissue changes on the way to malignancy.

PMID- 8138977
TI  - HLA-antigens in oral submucous fibrosis.
AB  - HLA-typing was carried out on 122 areca nut chewers who attended hospitals for
      complaints unrelated to the habit. The subjects were South Africans of Indian
      extraction. The study did not include haplotypes. Palpable fibrous bands in the
      mouth indicated oral submucous fibrosis. The subjects were divided into 4 groups
      based on specific oral symptoms and signs. Groups A and B were without fibrous
      bands. Group A (47 subjects) included those with one or no symptoms while group B
      (28 subjects) suffered from 2 to 7 oral symptoms. Group C (17 subjects) had oral
      symptoms and represented early or mild oral submucous fibrosis and exhibited at
      least one discrete palpable fibrous band. Group D (30 subjects) were classic oral
      submucous fibrosis cases with multiple bands. The high occurrence of oral
      submucous fibrosis in this study group (39%) is similar to the occurrence in
      comparable age groups reported earlier in South Africa and is conceivably due to
      the higher age range of the subjects and their relatively long exposure to the
      areca nut. We were unable to demonstrate a specific pattern of HLA-antigen
      frequencies in chewers with or without the disease. Furthermore, there were no
      differences between the study population and the controls. It is concluded that
      there is not necessarily a HLA-associated susceptibility in oral submucous
      fibrosis.

PMID- 8138978
TI  - Alteration in peripheral blood mononuclear cell function and serum cytokines in
      oral lichen planus.
AB  - Different activation parameters of peripheral blood mononuclear cells (PBMC) from
      31 patients with oral lichen planus (OLP) were examined and compared with 23
      healthy donors. Impaired spontaneous (450 +/- 241 vs 1290 +/- 480 cpm) and
      mitogen-induced (39580 +/- 14470 vs 67000 +/- 11810 cpm) lymphocyte blastogenesis
      was observed in OLP patients. Furthermore, reduced cytokine production was found
      after phytohemagglutinin A (PHA) stimulation for all cytokines studied-tumour
      necrosis factor alpha (TNF alpha, 432.2 +/- 73.4 vs 979.8 +/- 46.3 units/ml),
      interleukin 2 (IL-2, 156.2 +/- 14.9 vs 572.6 +/- 12.9 pg/ml), interferon gamma
      (IFN gamma, 48.5 +/- 11.9 vs 82.6 +/- 12.4 pg/ml) and interleukin 6 (IL-6, 253.6
      +/- 57.7 vs 1,419.0 +/- 279.6 units/ml)-except for interleukin 1 beta (IL-1 beta)
      and lymphotoxin (LT). In contrast, unstimulated culture supernatants showed
      increased TNF alpha (38.2 +/- 13.1 vs 8.0 +/- 0.2 units/ml), LT (10.2 +/- 2.2
      units/ml vs < 0.4) and IL-6 (18.5 +/- 5.6 units/ml vs < 0.5) activity. Similarly,
      elevated concentrations of TNF alpha (19.6 +/- 6.3 units/ml) and IL-6 (22.9 +/-
      4.7 units/ml) were detected in the sera of OLP patients. Combination of PHA and
      phorbol myristate acetate (PMA) could restore OLP proliferative T cell response
      and cytokine production to the level of healthy donors, whereas exogenous
      recombinant human IL-2 (rhuIL-2) plus PMA did not seem to be an effective
      stimulant for OLP T cells. These results indicate an alteration in the immune
      condition of OLP patients and an impairment in T lymphocyte function.

PMID- 8138979
TI  - Stereological and immunohistochemical study of development of human fetal labial
      salivary glands and their S-100 protein reactivity.
AB  - Stereological and certain histochemical aspects of fetal growth and development
      of human labial salivary glands are reported. Stereological analysis showed a
      highly significant progressive increase in proportional gland volume occupied by
      acini from 27% at 20 weeks to 56% at 38 weeks (P < 0.0001), and a comparable
      having of the relative gland volume occupied by connective tissue in the same
      period (P < 0.0001). Linear regression fitted the data well (r2 = 0.59 and 0.47
      respectively, n = 46). The change in relative volume occupied by ducts or by
      vascular tissue was small and did not reach significance. S-100 protein
      reactivity was demonstrated in the cytoplasm of cells of the labial gland
      primordia from their origin. As gland differentiation progressed, the S-100
      reactivity became localized in basophil acinar cells and in proximal
      (intercalated and intralobular), but not in distal, duct cells. A gradual
      increase in intensity of S-100 protein activity at these sites during salivary
      gland development was observed. Morphological maturity seems to be complete
      before 29 weeks but myoepithelial cells could not be identified with certainty.

PMID- 8138980
TI  - Ameloblastomas in the horse: a critical review and report of an additional
      example.
AB  - Previously published cases of ameloblastoma in the horse are reviewed in detail
      for their acceptability as examples of that tumor; an additional one is
      described. So far, this rare equine lesion has been shown to have two histologic
      patterns. The first consists of islands and sheets of epithelium that exhibit the
      basal cell characteristics of ameloblastoma; the central cells comprise stellate
      reticulum. The second exhibits these basal cell features less markedly and the
      central cells are spindle-shaped and closely packed. The biologic behavior of the
      equine ameloblastoma is thought to be the same as in human beings, a slowly
      growing, invasive lesion that does not metastasize. However, this conclusion
      requires confirmation.

PMID- 8138981
TI  - Oral leishmaniasis and Kaposi's sarcoma in an AIDS patient.
AB  - In the Mediterranean basin area, visceral leishmaniasis is an endemic disease
      caused by Leishmania donovani infantum. This study describes the clinical and
      pathological features of one patient with AIDS who had oral (tonsillar)
      leishmaniasis, caused by a viscerotropic zymodeme, concurrent with a Kaposi's
      sarcoma and with a CMV infection.

PMID- 8138982
TI  - Exteriorized chronic aorto-caval arteriovenous access shunts in the baboon (Papio
      cynocephalus).
AB  - A chronic arteriovenous (AV) blood access shunt has been developed in baboons. It
      is composed of silicone rubber tubing extensions bonded to vascular graft
      polytetrafluoroethylene (ePTFE) cuffs, for creating anastomoses with the distal
      aorta and inferior vena cava. Following surgical implantation, shunts remain
      patent for months (X = 9 +/- 2.5 months) and provides long-term ex vivo access to
      non-anticoagulated blood (Mean Blood Flow = 312 +/- 69 mL/min).

PMID- 8138983
TI  - Urinary enzyme concentrations in the owl monkey (Aotus nancymae).
AB  - The activity of three urinary enzymes, alkaline phosphatase (ALP), aspartate
      aminotransferase (AST), and N-acetyl-beta-D-glucosaminidase (NAG), was evaluated
      in 71 adult owl monkeys. Fifty-six animals had normal renal function, while 15
      had evidence of renal dysfunction. Urinary enzyme: urinary creatinine ratios (UE:
      UCr) were also determined. The activity for NAG was similar to that of other
      species, while ALP and AST were higher. Regression analyses revealed that urinary
      enzymes and UE:UCr were significantly correlated (P < or = 0.0001) with indices
      of renal damage and could identify active renal disease.

PMID- 8138984
TI  - A semi-natural habitat for housing small, nonhuman primates.
AB  - A semi-natural habitat that was designed to house a social group of squirrel
      monkeys (Saimiri sciureus sciureus) at Goucher College, in Maryland is described.
      The design could be readily adapted for use with other small primate species.

PMID- 8138985
TI  - Cryopreservation of vervet monkey semen and recovery of progressively motile
      spermatozoa.
AB  - A method to cryopreserve semen from the Vervet monkey (Cercopithecus aethiops)
      has been developed, yielding a mean post thaw recovery of 63.60% of pre-freeze
      progressive motility. The extender contained a TES-TRIS buffer, egg yolk,
      dextrose, streptomycin, penicillin, and glycerol as cryoprotectant. The pH ranged
      from 7.10-7.18 and the osmolality was 330-345 mOsmol/L.

PMID- 8138986
TI  - A comparison of morphometry from captive and free-ranging Macaca mulatta.
AB  - The paper addresses the effect of captivity on body size in Macaca mulatta,
      comparing a captive with the free-ranging population from which it was derived.
      The captive population, which was housed socially, was smaller in most linear
      measures and in body mass, particularly in young up to 13 month old animals.
      Nutritional differences in the diet may be at least partially responsible; the
      captive population was fed a lower level of total protein. Measurements for
      captive individuals < 24 hours to 36 months old are discussed in detail.

PMID- 8138987
TI  - Comparison of blood and urine analytes between two karyotypes of owl monkey,
      Aotus nancymae and Aotus vociferans.
AB  - Serum and urine analytes were compared between two karyotypes of owl monkey,
      Aotus nancymae and A. vociferans, to determine if normative clinical pathology
      data obtained from one karyotype were applicable to the other. Statistically
      significant differences (P < or = 0.05) were noted in serum calcium, serum
      phosphorus, serum sodium, serum potassium, serum urea nitrogen, urine calcium,
      calcium clearance, and fractional clearance of calcium between the two
      karyotypes. The results suggest that A. vociferans regulate calcium-phosphorus
      and electrolyte homeostasis in a manner different from that of A. nancymae.

PMID- 8138988
TI  - Methods for timing of pregnancy and monitoring of fetal body and brain growth in
      squirrel monkeys.
AB  - In order to obtain timed pregnancies in squirrel monkeys and to monitor
      development of the size of the fetus and its brain, tests were made of various
      combinations of vaginal examination, bioassay of chorionic gonadotropin (CG),
      measurement of maternal body weight and uterine fundus height during pregnancy,
      and determination of fetal biparietal diameter by ultrasonography and magnetic
      resonance imaging. The usefulness of these methods in developmental and
      teratological studies is discussed.

PMID- 8138990
TI  - An influenza A (H1N1) virus, closely related to swine influenza virus,
      responsible for a fatal case of human influenza.
AB  - In July 1991, an influenza A virus, designated A/Maryland/12/91 (A/MD), was
      isolated from the bronchial secretions of a 27-year-old animal caretaker. He had
      been admitted to the hospital with bilateral pneumonia and died of acute
      respiratory distress syndrome 13 days later. Antigenic analyses with
      postinfection ferret antisera and monoclonal antibodies to recent H1 swine
      hemagglutinins indicated that the hemagglutinin of this virus was antigenically
      related to, but distinguishable from, those of other influenza A (H1N1) viruses
      currently circulating in swine. Oligonucleotide mapping of total viral RNAs
      revealed differences between A/MD and other contemporary swine viruses. However,
      partial sequencing of each RNA segment of A/MD demonstrated that all segments
      were related to those of currently circulating swine viruses. Sequence analysis
      of the entire hemagglutinin, nucleoprotein, and matrix genes of A/MD revealed a
      high level of identity with other contemporary swine viruses. Our studies on A/MD
      emphasize that H1N1 viruses in pigs obviously continue to cross species barriers
      and infect humans.

PMID- 8138989
TI  - Evolution of the oncogenic potential of v-rel: rel-induced expression of
      immunoregulatory receptors correlates with tumor development and in vitro
      transformation.
AB  - v-rel is a viral oncogene that evolved from turkey c-rel, an NF-kappa B-related
      transcription factor. Numerous structural alterations record the evolutionary
      selection of v-rel and distinguish it from c-rel. To evaluate the biological
      significance of these alterations, we constructed a set of five c/v-rel hybrids
      in which three mutation clusters (c-Rel amino acids 1 to 97,222 to 302, and 328
      to 598) were differentially distributed. These constructs, in addition to
      parental v-rel and c-rel and two C-terminal deletion mutants of c-rel, were
      expressed from a retroviral vector. An analysis of cells infected with each of
      the nine viruses revealed that mutations in all three domains contributed to the
      ability of v-rel to induce two endogenous c-rel target genes, major
      histocompatibility complex (MHC) class I and class II, in the B-cell line DT95 as
      well as MHC class II in normal splenocytes. The analysis revealed a strong
      nonlinear correlation between the ability of a Rel protein to induce expression
      of MHC proteins and its capacity to produce splenic tumors and establish in vitro
      transformation. This correlation is consistent with the hypothesis that v-rel
      transforms by constitutively altering expression of genes regulated by c-rel and
      in this way simulates events associated with immune response-linked proliferation
      of cells of hematopoietic origin. Further, the 16 carboxy-terminal amino acids of
      c-Rel were identified as a domain responsible for producing a cytotoxic and/or
      cytostatic effect in DT95. Because this effect is likely to differentially
      influence induction of MHC expression and tumorigenesis/transformation, it may
      represent one factor that contributes to the nonlinearity of their correlation.

PMID- 8138991
TI  - Recovery from Friend disease in mice with reduced major histocompatibility
      complex class I expression.
AB  - Mice homozygous for the b allele of the MHC gene, H-2D, have a high incidence of
      recovery from Friend virus infections, while mice heterozygous for the b allele
      at H-2D have a very low incidence of recovery. Previous experiments indicated
      that the low recovery rates associated with heterozygosity at H-2D might be
      related to a gene dosage effect requiring the expression of two H-2Db alleles for
      high recovery. We investigated the effects of reduced H-2Db expression on
      recovery from Friend disease by using H-2b homozygous mice carrying a single beta
      2-microglobulin gene disruption. These mice had reductions in cell surface H-2Db
      expression comparable to those of H-2Da/b heterozygotes. Numerous cell types with
      various levels of H-2Db expression were examined, and in each case, the
      expression levels in the beta 2-microglobulin mutants closely reflected those
      observed in the H-2Da/b heterozygotes. We found, however, that reduced expression
      did not affect recovery from Friend disease, indicating that heterozygous levels
      of H-2Db expression are sufficient for the high-recovery phenotype previously
      associated only with H-2Db homozygotes.

PMID- 8138993
TI  - A cell surface protein that binds avian hepatitis B virus particles.
AB  - We have identified a 180-kDa cellular glycoprotein (gp180) that binds with high
      affinity to duck hepatitis B virus (DHBV) particles. The protein was detected by
      coprecipitating labeled duck hepatocyte proteins with virions or recombinant DHBV
      envelope proteins, using nonneutralizing monoclonal antibodies to the virion
      envelope. Binding of gp180 requires only the pre-S region of the viral large
      envelope protein, since recombinant fusion proteins bearing only this region
      efficiently coprecipitate gp180. The DHBV-gp180 interaction is blocked by two
      independent neutralizing monoclonal antibodies. The protein is found on both
      internal and surface membranes of the cell, and the species distribution of gp180
      binding activity mirrors the known host range of DHBV infection. Functional gp180
      is expressed in a wide variety of tissues in susceptible ducks.

PMID- 8138992
TI  - Transformation of avian fibroblasts overexpressing the c-rel proto-oncogene and a
      variant of c-rel lacking 40 C-terminal amino acids.
AB  - The v-rel oncogene was derived from the c-rel proto-oncogene, which encodes a
      transcriptional activator. Expression of v-rel transforms avian hematopoietic
      cells and fibroblasts. Here we report that overexpression (via a replication
      competent retroviral vector) of full-length c-Rel as well as a 40-amino-acid,
      carboxy-terminal deletion construct of c-Rel (c-Rel delta) resulted in the
      morphological transformation of chicken embryo fibroblasts (CEFs). Subcellular
      localization of Rel polypeptides in these transformed cells as determined by
      immunofluorescence and immunoprecipitation revealed their presence in both the
      nucleus and the cytoplasm, with the majority of Rel polypeptides showing
      cytoplasmic localization. Cytoplasmic localization could be due to interaction
      with I kappa B molecules, and in fact, the overexpression of c-Rel or the C
      terminal deletion construct of c-Rel resulted in an increase in the levels of
      mRNA encoding the avian I kappa B protein pp40 and the avian homolog of the NF
      kappa B protein, p105. However, expression of v-Rel resulted in the induction of
      pp40 mRNA only. While c-Rel was a weak activator of kappa B-mediated
      transcription of a reporter construct in transformed CEFs, v-Rel and c-Rel delta
      were transcriptional repressors. However, in spite of these differences, all of
      these proteins resulted in the transformation of CEFs.

PMID- 8138994
TI  - In vivo cooperation of two nuclear oncogenic proteins, P135gag-myb-ets and
      p61/63myc, leads to transformation and immortalization of chicken myelomonocytic
      cells.
AB  - To investigate a possible in vivo cooperation between the p61/63myc and P135gag
      myb-ets proteins, we used a previously constructed retrovirus, named MHE226,
      which contains the fused v-myb and v-ets oncogenes of the E26 retrovirus and the
      v-myc oncogene of MH2. For that purpose, chicken neuroretina cells producing
      MHE226 and pseudotyped with the Rous associated virus-1 (RAV-1) helper virus were
      injected in 1-day-old chickens. In control experiments, we also injected chicken
      neuroretina cells producing E26 (RAV-1), RAV-1 alone, or constructs lacking one
      of the oncogenes of MHE226. The average life span of MHE226-infected chickens is
      half that of E26-infected chickens. MHE226-infected chickens harbor tumors
      scattered in many organs, but compared with E26, MHE226 induced a weak leukemia.
      Study of integration sites suggests that the majority of the tumors results from
      clonal or oligoclonal events. Cell cultures were derived from the tumors of
      MHE226-infected chickens and grown in standard medium without addition of
      exogenous chicken myelomonocytic growth factor. These cells still divide at high
      rate after more than 100 passages and can thus be considered immortalized. By
      using several criteria, these cells were characterized as precursors of the
      myelomonocytic lineages.

PMID- 8138995
TI  - A human cytomegalovirus early promoter with upstream negative and positive cis
      acting elements: IE2 negates the effect of the negative element, and NF-Y binds
      to the positive element.
AB  - The human cytomegalovirus early promoter for the UL4 gene, which codes for an
      early viral envelope glycoprotein designated gpUL4, requires immediate-early
      viral protein two (IE2) synthesis to be activated (C.-P. Chang, C. L. Malone, and
      M. F. Stinski, J. Virol. 63:281, 1989). We investigated the cis-acting and trans
      acting factors that regulate transcription from this UL4 promoter. In transient
      transfection assays, the viral IE2 protein negated the effect of an upstream cis
      acting negative element and enhanced downstream gene expression. A cis-acting
      positive element contributed to the activity of the viral promoter when an
      upstream cis-acting negative element was deleted or when the viral IE2 protein
      was present. The cellular protein(s) that binds to the cis-acting negative
      element requires further investigation. The cellular protein that binds to the
      cis-acting positive element was characterized. Two DNA sequence-specific protein
      complexes were detected with DNA probes spanning the region containing the cis
      acting positive element and human cytomegalovirus-infected human fibroblast cell
      nuclear extracts. The more slowly migrating complex was labeled complex A, and
      the faster was labeled complex B. Only complex B was detected with mock-infected
      cell nuclear extracts. Competition experiments confirmed the specificity of the A
      and B complexes. The protein bound to the DNA in both the complexes contacts a
      CCAAT box imperfect dyad symmetry (5'CCAATCACTGG3'). Either CCAAT box within the
      dyad symmetry could compete for binding the nuclear factor. Mutation of the CCAAT
      box dyad symmetry resulted in a decrease of the transcriptional activity from the
      UL4 promoter. A cellular transcription factor, antigenically related to nuclear
      factor-Y (NF-Y), was found in both complexes A and B. Events associated with
      viral infection caused phosphorylation of protein complex A. Dephosphorylation of
      the DNA-binding protein converts complex A to complex B. The effect of
      phosphorylation of NF-Y is not known.

PMID- 8138996
TI  - Expression of seven herpes simplex virus type 1 glycoproteins (gB, gC, gD, gE,
      gG, gH, and gI): comparative protection against lethal challenge in mice.
AB  - We have constructed recombinant baculoviruses individually expressing seven of
      the herpes simplex virus type 1 (HSV-1) glycoproteins (gB, gC, gD, gE, gG, gH,
      and gI). Vaccination of mice with gB, gC, gD, gE, or gI resulted in production of
      high neutralizing antibody titers to HSV-1 and protection against intraperitoneal
      and ocular challenge with lethal doses of HSV-1. This protection was
      statistically significant and similar to the protection provided by vaccination
      with live nonvirulent HSV-1 (90 to 100% survival). In contrast, vaccination with
      gH produced low neutralizing antibody titers and no protection against lethal HSV
      1 challenge. Vaccination with gG produced no significant neutralizing antibody
      titer and no protection against ocular challenge. However, gG did provide modest,
      but statistically significant, protection against lethal intraperitoneal
      challenge (75% protection). Compared with the other glycoproteins, gG and gH were
      also inefficient in preventing the establishment of latency. Delayed-type
      hypersensitivity responses to HSV-1 at day 3 were highest in gG-, gH-, and gE
      vaccinated mice, while on day 6 mice vaccinated with gC, gE, and gI had the
      highest delayed-type hypersensitivity responses. All seven glycoproteins produced
      lymphocyte proliferation responses, with the highest response being seen with gG.
      The same five glycoproteins (gB, gC, gD, gE, and gI) that induced the highest
      neutralization titers and protection against lethal challenge also induced some
      killer cell activity. The results reported here therefore suggest that in the
      mouse protection against lethal HSV-1 challenge and the establishment of latency
      correlate best with high preexisting neutralizing antibody titers, although there
      may also be a correlation with killer cell activity.

PMID- 8138997
TI  - trans-dominant interference of type 5 adenovirus E1a mutants in cell
      transformation.
AB  - Two type 5 adenovirus (Ad5) early region 1a (E1a) mutants, H5in104 and H5dl105,
      were impaired in viral replication and cell transformation. In addition, these
      mutants trans dominantly inhibited the frequency with which H5sub309, a
      phenotypically wild-type mutant, and H5dl520, a high-frequency transformation
      mutant, transformed CREF cells. Inhibition of transformation varied in proportion
      to the input ratio of mutant to coinfecting virus. It was found that H5in104, but
      not H5dl105, could not complement Ad5 E1b mutants that failed to synthesize 19-
      or 55-kDa E1b product. H5dl105 yielded 10-fold less virus than the wild-type did
      in 293 cells, which constitutively express E1a and E1b products; similar low
      yields were also observed with H5in104 and H5dl105 in another E1a- and E1b
      expressing transformed cell line, KB16. Marker rescue and DNA sequence analyses,
      however, indicated that the phenotypes of H5in104 and H5dl105 were the result of
      their respective E1a mutations. The data presented are the first to demonstrate
      that mutants of animal viruses can effect dominant interference with the viral
      function(s) that produce cell transformation.

PMID- 8138998
TI  - Differential regulation of the JE gene encoding the monocyte chemoattractant
      protein (MCP-1) in cervical carcinoma cells and derived hybrids.
AB  - Malignant human papillomavirus type 18 (HPV18)-positive cervical carcinoma cells
      can be reverted to a nonmalignant phenotype by generation of somatic cell hybrids
      with normal human fibroblasts. Although nontumorigenic hybrids, their tumorigenic
      segregants, and the parental HeLa cells have similar in vitro properties,
      inoculation only of nontumorigenic cells into nude mice results in a selective
      suppression of HPV18 transcription which precedes cessation of cellular growth.
      Our present study, aimed at understanding the differential regulation in vitro
      and in vivo, shows that the JE gene, encoding the monocyte chemoattractant
      protein (MCP-1), is expressed only in nontumorigenic hybrids. Although the gene,
      including its regulatory region, is intact, no JE (MCP-1) mRNA is detected in the
      tumorigenic segregants and in other malignant HPV-positive cervical carcinoma
      cell lines. Tests of several monocyte-derived cytokines showed that only tumor
      necrosis factor alpha strongly induces the JE (MCP-1) gene in nontumorigenic
      cells and that this is accompanied by a dose-dependent reduction of HPV
      transcription. The JE (MCP-1) up-regulation occurs within 2 h and does not
      require de novo protein synthesis. The response to tumor necrosis factor alpha
      seems to be mediated by an NF-kappa B-related mechanism, since the induction can
      be completely abrogated by pretreating the cells with an antioxidant such as
      pyrrolidine dithiocarbamate. Interestingly, cocultivation of nonmalignant hybrids
      with monocyte-enriched fractions from human peripheral blood also results in an
      induction of the JE (MCP-1) gene and a concomitant suppression of HPV18
      transcription. Neither effect is observed in malignant cells. These data suggest
      that JE (MCP-1) may play a pivotal role in the intercellular communication by
      triggering an intracellular pathway which negatively interferes with viral
      transcription in HPV-positive nontumorigenic cells.

PMID- 8138999
TI  - Defective endogenous proviruses are expressed in feline lymphoid cells: evidence
      for a role in natural resistance to subgroup B feline leukemia viruses.
AB  - Endogenous feline leukemia virus (FeLV)-related sequences (enFeLV) are a family
      of proviral elements found in domestic cats and their close relatives. These
      elements can recombine with exogenous, infectious FeLVs of subgroup A (FeLV-A),
      giving rise to host range variants of FeLV-B. We found that a subset of defective
      enFeLV proviruses is highly expressed in lymphoma cell lines and in a variety of
      primary tissues, including lymphoid tissues from healthy specific-pathogen-free
      cats. At least two RNA species were detected, a 4.5-kb RNA containing gag, env,
      and long terminal repeat sequences and a 2-kb RNA containing env and long
      terminal repeat sequences. Cloning of enFeLV cDNA from two FeLV-free lymphoma
      cell lines (3201 and MCC) revealed a long open reading frame (ORF) encoding a
      truncated env gene product corresponding to the N-terminal portion of gp70env.
      Interestingly, all of three natural FeLV-B isolates include 3' env sequences
      which are missing from the highly transcribed subset and hence must be derived
      from other enFeLV elements. The enFeLV env ORF cDNA clones were closely similar
      to a previously characterized enFeLV provirus, CFE-16, but were polymorphic at a
      site corresponding to an exogenous FeLV neutralization epitope. Site-specific
      antiserum raised to a C-terminal 30-amino-acid peptide of the enFeLV env ORF
      detected an intracellular product of 35 kDa which was also shed from cells in
      stable form. Expression of the 35-kDa protein correlated with enFeLV RNA levels
      and was negatively correlated with susceptibility to infection with FeLV-B. Cell
      culture supernatant containing the 35-kDa protein specifically blocked infection
      of permissive fibroblast cells with FeLV-B isolates. We suggest that the
      truncated env protein mediates resistance by receptor blockade and that this form
      of enFeLV expression mediates the natural resistance of cats to infection with
      FeLV-B in the absence of FeLV-A.

PMID- 8139000
TI  - Genetic analysis of human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2)
      mixed infections in India reveals a recent spread of HIV-1 and HIV-2 from a
      single ancestor for each of these viruses.
AB  - DNA sequences encoding the surface envelope glycoproteins of human
      immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) were amplified by PCR
      from uncultured peripheral blood mononuclear cells obtained from patients with
      serologically defined HIV-1/HIV-2 mixed infections from Bombay, India. HIV-1
      specific PCR products were obtained in seven of seven randomly chosen doubly
      reactive cases, while HIV-2-specific sequences were detected in five of seven
      cases (71%). DNA sequence analysis showed that the HIV-1 gp120 coding sequences
      were closely related to each other (nucleotide sequence divergence of between 3.1
      and 6.8%). Phylogenetic tree analysis placed the Indian strains within the C
      subtype of HIV-1, being most similar to sequences previously found in East and
      South Africa. The HIV-2 sequences were also closely related to each other, with
      an overall sequence divergence of between 5.6 and 10.5%. The low level of
      nucleotide divergence among Indian HIV-1 and HIV-2 sequences suggests a fairly
      recent introduction of each virus into this population from a single point of
      entry in each case. The HIV-2 sequences reported here represent the first
      analysis of Asian HIV-2 strains and confirm the serological pattern previously
      detected in India. These data show that a substantial spread of HIV-2, together
      with HIV-1, has appeared outside Africa in a population hitherto unexposed to
      HIV. These findings imply that further spread of HIV-2 worldwide is to be
      expected and have important implications for future vaccine and therapy
      development.

PMID- 8139001
TI  - Mutation of either of two cysteine residues or deletion of the amino or carboxy
      terminus of nonstructural protein NS1 of bluetongue virus abrogates virus
      specified tubule formation in insect cells.
AB  - Virus-specific tubules are characteristic of orbivirus infections and are likely
      to play an important role in virus morphogenesis. It has been shown that for
      bluetongue virus (BTV), the prototype orbivirus in the family Reoviridae, the
      virus-encoded NS1 protein forms tubules in insect cells when the BTV segment M6
      gene is expressed by using a baculovirus vector. To understand the function of
      NS1 tubules and to identify the sequences involved in their polymerization, a
      series of mutant NS1 genes was generated and expressed in insect cell cultures by
      using baculovirus vectors. Three of the mutants were deletion mutants. One
      (AcNS1.dNT10) lacked 10 of the amino-terminal amino acids, and the other two
      mutants (AcNS1.dCT20 and AcNS1.dCT43) lacked 20 or 43 of the carboxy-terminal
      amino acids. In addition, site-directed mutants were constructed in which various
      single cysteines or pairs of cysteines were changed to serines. The ability of
      each mutant protein to form tubules was investigated. None of the deletion
      mutants formed tubules. The constructs in which the cysteines at amino acid
      positions 337 and/or 340 were replaced by serines (e.g., AcNS1.C337S,C340S) also
      did not form tubules. Instead, the NS1 protein of these and the deletion mutants
      made ribbon-like structures which formed large aggregates. Mutations involving
      six other cysteines (i.e., AcNS1.C37S,C43S,AcNS1.C462S,C465S, AcNS1.C104S, and
      AcNS1.C364S) produced tubules. The results show that both the amino and carboxy
      termini of the NS1 protein molecule and the cysteines at residues 337 and 340 are
      essential for tubule formation.

PMID- 8139002
TI  - Deletion and mutational analyses of bluetongue virus NS2 protein indicate that
      the amino but not the carboxy terminus of the protein is critical for RNA-protein
      interactions.
AB  - Genome segment 8 (S8) of bluetongue virus serotype 10 (BTV-10) encodes the
      nonstructural protein NS2. This protein, which has single-stranded RNA (ssRNA)
      binding capacity, is found in BTV-infected cells in the form of virus inclusion
      bodies (VIBs). To identify the domain(s) important for RNA binding and
      oligomerization of the protein, a number of deletions were made in regions of the
      gene that code for either the amino or carboxy terminus of the protein. The
      modified genes were cloned into and expressed from baculovirus vectors based on
      Autographa californica nuclear polyhedrosis virus. Truncated NS2 proteins were
      individually analyzed for the ability to bind ssRNA and to form VIBs. The results
      indicated that the carboxy terminus of the protein is involved neither in RNA
      binding nor in the formation of VIBs. The amino terminus of NS2 was shown to be
      essential for ssRNA binding but not for NS2 protein oligomerization. Point
      mutations that involved the substitution of various charged residues at the amino
      terminus of NS2 were generated and tested for the ability to bind ssRNA. The
      results showed that the arginines at amino acid residues 6 and 7 and the lysine
      at residue 4, but not the glutamic acid at residue 2, are involved in ssRNA
      binding.

PMID- 8139003
TI  - Characterization of the putative fusogenic domain in vesicular stomatitis virus
      glycoprotein G.
AB  - The envelope glycoprotein G of vesicular stomatitis virus induces membrane fusion
      at low pH. Site-directed mutagenesis of specific amino acids within a segment
      spanning amino acids 123 to 137 of G protein, which is highly conserved in
      vesiculoviruses and was previously shown by us to be involved in fusogenic
      activity (Y. Li, C. Drone, E. Sat, and H. P. Ghosh, J. Virol. 67:4070-4077,
      1993), was used to determine the role of this region in low-pH-induced membrane
      fusion. The mutant glycoproteins expressed in COS cells were assayed for acid-pH
      induced cell-cell fusion. Substitution of the variant Pro-123 with Leu had no
      effect on the fusogenic activity, while substitution of conserved Phe-125 and Asp
      137 with Tyr and Asn, respectively, shifted the pH optimum of membrane fusion to
      a more acidic pH value and decreased the fusion efficiency. The deletion of amino
      acid residues 124 to 127, 131 to 137, or 124 to 137 produced mutants defective in
      transport. Mutation of the conserved residues Gly-124 and Pro-127 to Ala and to
      Gly or Leu, respectively, inhibited cell-cell fusion activity by about 90%
      without affecting transport of the mutant proteins to the cell surface,
      suggesting that these two residues may be present within the fusion peptide and
      thus may be directly involved in fusion. This highly conserved domain containing
      neutral amino acids of G protein may therefore represent the putative fusion
      domain of vesicular stomatitis virus G protein.

PMID- 8139004
TI  - Nucleotide sequence and structural determinants of specific binding of coat
      protein or coat protein peptides to the 3' untranslated region of alfalfa mosaic
      virus RNA 4.
AB  - The specific binding of alfalfa mosaic virus coat protein to viral RNA requires
      determinants in the 3' untranslated region (UTR). Coat protein and peptide
      binding sites in the 3' UTR of alfalfa mosaic virus RNA 4 have been analyzed by
      hydroxyl radical footprinting, deletion mapping, and site-directed mutagenesis
      experiments. The 3' UTR has several stable hairpins that are flanked by single
      stranded (A/U)UGC sequences. Hydroxyl radical footprinting data show that five
      sites in the 3' UTR of alfalfa mosaic virus RNA 4 are protected by coat protein,
      and four of the five protected regions contain AUGC or UUGC. Electrophoretic
      mobility band shift results suggest four coat protein binding sites in the 3'
      UTR. A 3'-terminal 39-nucleotide RNA fragment containing four AUGC repeats bound
      coat protein and coat protein peptides with high affinity; however, coat protein
      bound poorly to antisense 3' UTR transcripts and poly(AUGC)10. Site-directed
      mutagenesis of AUGC865-868 resulted in a loss of coat protein binding and peptide
      binding by the RNA fragment. Alignment of alfalfa mosaic RNA sequences with those
      from several closely related ilarviruses demonstrates that AUGC865-868 is
      perfectly conserved; moreover, the RNAs are predicted to form similar 3'-terminal
      secondary structures. The data strongly suggest that alfalfa mosaic virus coat
      protein and ilavirus coat proteins recognize invariant AUGC sequences in the
      context of conserved structural elements.

PMID- 8139005
TI  - Modulation of cyclin gene expression by adenovirus E1A in a cell line with E1A
      dependent conditional proliferation.
AB  - To investigate how adenovirus E1A controls cell proliferation, we have fused E1A
      to the hormone-binding domain of the human estrogen receptor (ER) and introduced
      the E1A-ER chimeric gene together with an activated ras gene into primary rat
      embryo fibroblasts. Cell lines derived from this transfection proliferate in an
      estrogen-dependent manner. Estrogen-dependent activation of E1A-ER led to a rapid
      induction of both cyclin E and cyclin A gene expression. In contrast, levels of
      cyclin D1 were strongly reduced by activation of E1A-ER. Similar changes in
      cyclin gene expression were observed when primary human fibroblasts were infected
      with wild-type adenovirus and when adenovirus E1A was stably expressed in NIH 3T3
      cells. Our findings suggest that activation of cyclin A and E, but not D1, gene
      expression by E1A precedes and may be responsible for E1A-dependent cell
      proliferation. In contrast, we found that quantitative disruption of complexes
      between the E2F transcription factor and the retinoblastoma protein is not
      required for E1A-dependent S-phase entry.

PMID- 8139006
TI  - Rous sarcoma virus integrase protein: mapping functions for catalysis and
      substrate binding.
AB  - Rous sarcoma virus (RSV), like all retroviruses, encodes an integrase protein
      that is responsible for covalently joining the reverse-transcribed viral DNA to
      host DNA. We have probed the organization of functions within RSV integrase by
      constructing mutant derivatives and assaying their activities in vitro. We find
      that deletion derivatives lacking the amino-terminal 53 amino acids, which
      contain the conserved H-X(3-7)-H-X(23-32)-C-X(2)-C (HHCC) Zn(2+)-binding motif,
      are greatly impaired in their ability to carry out two reactions characteristic
      of integrase proteins: specific cleavage of the viral DNA termini and DNA strand
      transfer. Deletion mutants lacking the carboxyl-terminal 69 amino acids are also
      unable to carry out these reactions. However, all deletion mutants that retain
      the central domain are capable of carrying out disintegration, an in vitro
      reversal of the normal DNA strand transfer reaction, indicating that the
      catalytic center probably lies within this central region. Another conserved
      motif, D-X(39-58)-D-X(35)-E, is found in this central domain. These findings with
      RSV integrase closely parallel previous findings with human immunodeficiency
      virus integrase, indicating that a modular catalytic domain is a general feature
      of this family of proteins. Surprisingly, and unlike results obtained so far with
      human immunodeficiency virus integrase, efficient strand transfer activity can be
      restored to a mutant RSV integrase lacking the amino-terminal HHCC domain by
      fusion to various short peptides. Furthermore, these fusion proteins retain the
      substrate specificity of RSV integrase. These data support a model in which the
      integrase activities required for strand transfer in vitro, including substrate
      recognition, multimerization, and catalysis, all lie primarily outside the amino
      terminal HHCC domain.

PMID- 8139007
TI  - Human immunodeficiency virus type 1 Rev-responsive element RNA binds to host cell
      specific proteins.
AB  - RNase protection-gel retention studies show human host cell-specific
      ribonucleoprotein complexes with human immunodeficiency virus type 1 Rev
      responsive element (RRE) RNA. Nuclear proteins from rodent or murine cells appear
      to lack the ability to form these complexes. Human-mouse somatic cell hybrids
      retaining a single human chromosome, either 6 or 12, form the RRE-nuclear-protein
      complexes. One of the complexes requires the entire RRE RNA, while the other
      needs RRE RNA stem-loops 1 and 2 only. Two major proteins with molecular masses
      of 120 and 62 kDa specifically bind to RRE RNA. Rodent cells (CHO) either lack or
      contain small amounts of these RRE-binding proteins.

PMID- 8139008
TI  - Identification of three feline immunodeficiency virus (FIV) env gene subtypes and
      comparison of the FIV and human immunodeficiency virus type 1 evolutionary
      patterns.
AB  - Feline immunodeficiency virus (FIV) is a lentivirus associated with AIDS-like
      illnesses in cats. As such, FIV appears to be a feline analog of human
      immunodeficiency virus (HIV). A hallmark of HIV infection is the large degree of
      viral genetic diversity that can develop within an infected individual and the
      even greater and continually increasing level of diversity among virus isolates
      from different individuals. Our goal in this study was to determine patterns of
      FIV genetic diversity by focusing on a 684-nucleotide region encompassing
      variable regions V3, V4, and V5 of the FIV env gene in order to establish
      parallels and distinctions between FIV and HIV type 1 (HIV-1). Our data
      demonstrate that, like HIV-1, FIV can be separated into distinct envelope
      sequence subtypes (three are described here). Similar to that found for HIV-1,
      the pairwise sequence divergence within an FIV subtype ranged from 2.5 to 15.0%,
      whereas that between subtypes ranged from 17.8 to 26.2%. However, the high number
      of synonymous nucleotide changes among FIV V3 to V5 env sequences may also
      include a significant number of back mutations and suggests that the evolutionary
      distances among FIV subtypes are underestimated. Although only a few subtype B
      viruses were available for examination, the pattern of diversity between the FIV
      A and B subtypes was found to be significantly distinct; subtype B sequences had
      proportionally fewer mutations that changed amino acids, compared with silent
      changes, suggesting a more advanced state of adaptation to the host. No similar
      distinction was evident for HIV-1 subtypes. The diversity of FIV genomes within
      individual infected cats was found to be as high as 3.7% yet twofold lower than
      that within HIV-1-infected people over a comparable region of the env gene.
      Despite these differences, significant parallels between patterns of FIV
      evolution and HIV-1 evolution exist, indicating that a wide array of potentially
      divergent virus challenges need to be considered in FIV vaccine and pathogenesis
      studies.

PMID- 8139010
TI  - Functional role of the V1/V2 region of human immunodeficiency virus type 1
      envelope glycoprotein gp120 in infection of primary macrophages and soluble CD4
      neutralization.
AB  - We have examined the influence of the V1/V2 region of the human immunodeficiency
      virus type 1 (HIV-1) gp120 on certain biologic properties of the virus. We
      observed that on the genomic background of the T-cell-line-tropic strain, HIV
      1SF2mc, both the V1 and V2 domains of the macrophage-tropic strain, HIV-1SF162mc,
      in addition to the required V3 domain, are necessary to attain full macrophage
      tropism. Furthermore, the V2 domain modulates the sensitivity of HIV-1 to soluble
      CD4 neutralization. Structural studies of recombinant and mutant envelope
      glycoproteins suggest that the function of the V1/V2 region is to interact with
      the V3 domain and confer on the envelope gp120 of HIV-1SF2mc a conformation more
      similar to that of the macrophage-tropic strain HIV-1SF162mc. The conformation of
      the envelope gp120 appears to be strain specific and plays an important role in
      determining HIV-1 tissue tropism and sensitivity to soluble CD4 neutralization.

PMID- 8139009
TI  - A novel latency-active promoter is contained within the herpes simplex virus type
      1 UL flanking repeats.
AB  - Herpes simplex virus type 1 (HSV-1) expresses a unique series of RNA molecules,
      the latency-associated transcripts or LATs, during latent infection of neuronal
      tissues. Previous studies by others have described a TATA box-containing latency
      active promoter, referred to here as LAP1, located approximately 700 bp upstream
      of the 5' end of the major 2.0-kb LAT. In this report, transient gene expression
      assays were employed to identify a second, novel latency-active promoter (LAP2)
      present within a region downstream of LAP1 and 5' proximal to the major 2.0-kb
      LAT. In contrast to LAP1, this promoter lacks a TATA box but possesses cis-acting
      regulatory elements and other features frequently observed within eukaryotic
      housekeeping gene promoters. Unlike most other HSV promoters, LAP2 was down
      regulated by the viral transcriptional activators ICP4 and ICP0. The majority of
      LAP2-positive regulatory elements were located within sequences from -257 to -58
      relative to the 5' end of the 2.0-kb LAT, and the basal promoter mapped within
      sequences from -14 to +28. RNase protection experiments demonstrated that
      chimeric LAT-chloramphenicol acetyltransferase transcripts produced in the
      transient assays initiated at or near the 5' end of the major 2-kb LAT. Tn5
      insertional mutagenesis of the ICP4 regulatory gene determined that down
      regulation of LAP2 required the ICP4 transactivating domain and targeted the
      minimal promoter region as the site of action by ICP4. Replicating recombinant
      viruses containing a LAP2-lacZ reporter gene cassette in an ectopic site
      (glycoprotein C locus) were shown to be active in mouse trigeminal ganglia. Taken
      together, these experiments suggest that the LAT region of the HSV-1 genome
      contains at least two latency-active promoters which may play different roles in
      expressing the various LATs. Alternatively, these promoters may comprise a larger
      promoter-regulatory complex which may influence transcription during latency.

PMID- 8139011
TI  - Differential activities of the human immunodeficiency virus type 1-encoded Vpu
      protein are regulated by phosphorylation and occur in different cellular
      compartments.
AB  - The human immunodeficiency virus type 1 (HIV-1)-specific Vpu is an 81-amino-acid
      amphipathic integral membrane protein with at least two different biological
      functions: (i) enhancement of virus particle release from the plasma membrane of
      HIV-1-infected cells and (ii) degradation of the virus receptor CD4 in the
      endoplasmic reticulum (ER). We have previously found that Vpu is phosphorylated
      in infected cells at two seryl residues in positions 52 and 56 by the ubiquitous
      casein kinase 2. To study the role of Vpu phosphorylation on its biological
      activity, a mutant of the vpu gene lacking both phosphoacceptor sites was
      introduced into the infectious molecular clone of HIV-1, pNL4-3, as well as
      subgenomic Vpu expression vectors. This mutation did not affect the expression
      level or the stability of Vpu but had a significant effect on its biological
      activity in infected T cells as well as transfected HeLa cells. Despite the
      presence of comparable amounts of wild-type and nonphosphorylated Vpu, decay of
      CD4 was observed only in the presence of phosphorylated wild-type Vpu.
      Nonphosphorylated Vpu was unable to induce degradation of CD4 even if the
      proteins were artificially retained in the ER. In contrast, Vpu-mediated
      enhancement of virus secretion was only partially dependent on Vpu
      phosphorylation. Enhancement of particle release by wild-type Vpu was efficiently
      blocked when Vpu was artificially retained in the ER, suggesting that the two
      biological functions of Vpu are independent, occur at different sites within a
      cell, and exhibit different sensitivity to phosphorylation.

PMID- 8139012
TI  - Membrane anchoring domain of herpes simplex virus glycoprotein gB is sufficient
      for nuclear envelope localization.
AB  - We have used the glycoprotein gB of herpes simplex virus type 1 (gB-1), which
      buds from the inner nuclear membrane, as a model protein to study localization of
      membrane proteins in the nuclear envelope. To determine whether specific domains
      of gB-1 glycoprotein are involved in localization in the nuclear envelope, we
      have used deletion mutants of gB-1 protein as well as chimeric proteins
      constructed by replacing the domains of the cell surface glycoprotein G of
      vesicular stomatitis virus with the corresponding domains of gB. Mutant and
      chimeric proteins expressed in COS cells were localized by immunoelectron
      microscopy. A chimeric protein (gB-G) containing the ectodomain of gB and the
      transmembrane and cytoplasmic domains of G did not localize in the nuclear
      envelope. When the ectodomain of G was fused to the transmembrane and cytoplasmic
      domains of gB, however, the resulting chimeric protein (G-gB) was localized in
      the nuclear envelope. Substitution of the transmembrane domain of G with the 69
      hydrophobic amino acids containing the membrane anchoring domain of gB allowed
      the hybrid protein (G-tmgB) to be localized in the nuclear envelope, suggesting
      that residues 721 to 795 of gB can promote retention of proteins in the nuclear
      envelope. Deletion mutations in the hydrophobic region further showed that a
      transmembrane segment of 21 hydrophobic amino acids, residues 774 to 795 of gB,
      was sufficient for localization in the nuclear envelope. Since wild-type gB and
      the mutant and chimeric proteins that were localized in the nuclear envelope were
      also retained in the endoplasmic reticulum, the membrane spanning segment of gB
      could also influence retention in the endoplasmic reticulum.

PMID- 8139013
TI  - Identification of factor-binding sites in the duck hepatitis B virus enhancer and
      in vivo effects of enhancer mutations.
AB  - Hepatitis B viruses (hepadnaviruses) can cause chronic, productive infections of
      hepatocytes. Analyses of the enhancers and promoters of these viruses in cell
      lines have suggested a requirement of these elements for liver-enriched
      transcription factors. In this study, a minimum of seven factor-binding sites on
      the duck hepatitis B virus enhancer were detected by DNase I footprinting using
      duck liver nuclear extracts. Among the sites that were tentatively identified
      were one C/EBP-, one HNF1-, and two HNF3-binding sites. Mutations of the HNF1-
      and HNF3-like sites, which eliminated factor binding, as assessed by both DNase I
      footprinting and competitive gel shift assays, were evaluated for their effects
      on enhancer activity. Using a construct in which human growth hormone was
      expressed from the viral enhancer and core gene promoter, we found that all of
      the mutations, either alone or in combination, reduced expression two- to
      fourfold in LMH chicken hepatoma cells. The mutations in the HNF1 site and one of
      the HNF3 sites, when inserted into the intact viral genome, also suppressed virus
      RNA synthesis in primary hepatocyte cultures. Virus carrying the latter HNF3
      mutation was also examined for its ability to infect and replicate in ducks. No
      significant inhibition of virus replication was observed in a short-term assay;
      however, virus with the HNF3 mutation was apparently unable to grow in the
      pancreas, a second site of duck hepatitis B virus replication in the duck.

PMID- 8139014
TI  - Tumor necrosis factor alpha promotes replication and pathogenicity of rat
      cytomegalovirus.
AB  - We investigated the role of tumor necrosis factor alpha (TNF-alpha) in the
      pathogenesis of rat cytomegalovirus (RCMV) infection. TNF-alpha levels found in
      the sera of radiation-immunosuppressed rats in the course of infection (> 350
      pg/ml) correlated with the development of RCMV disease. Administration of anti
      TNF-alpha antibodies strongly reduced the severity of pneumonia and led to a
      reduction in virus titers. In immunocompetent rats, anti-TNF-alpha antibodies
      also significantly suppressed viral replication. Conversely, administration of
      TNF-alpha augmented RCMV replication and aggravated the disease signs. In vitro,
      TNF-alpha enhanced RCMV replication in the macrophage, whereas a reduction of
      viral replication was observed in fibroblasts, indicating that the effect on
      viral replication is cell type specific. Besides activation of viral replication
      and exacerbation of RCMV disease, TNF-alpha also favored lymphoid and
      hematopoietic tissue reconstitution after irradiation, which may contribute to
      antiviral resistance and survival. This finding demonstrates the protean nature
      of TNF-alpha, with both beneficial and adverse effects for the host. Our results
      suggest that TNF-alpha plays an important role in modulating the pathogenesis of
      RCMV infection.

PMID- 8139015
TI  - Suppression of rat cytomegalovirus replication by antibodies against gamma
      interferon.
AB  - The role of gamma interferon (IFN-gamma) in the resolution of rat cytomegalovirus
      (RCMV) infection was investigated. In the spleen, IFN-gamma-producing cells
      reached maximum numbers on day 7 after infection. Prophylactic treatment with
      high doses of recombinant rat IFN-gamma exerted antiviral activity in fibroblasts
      and protected immunosuppressed rats against a lethal RCMV challenge. Remarkably,
      in immunocompetent rats, neutralization of endogenous IFN-gamma activity
      significantly reduced the numbers of RCMV antigen-expressing cells in the spleen,
      the predominant site of viral replication. Moreover, protection of radiation
      immunosuppressed infected rats by transferred immune T cells was enhanced by
      coinjection of IFN-gamma neutralizing antibodies. The observations were
      paralleled by in vitro findings: low concentrations of IFN-gamma enhanced viral
      replication in both macrophages and fibroblasts. These data suggest that IFN
      gamma can play different and even opposite roles in the regulation of RCMV
      replication in vivo; T lymphocytes may contribute to the progression of RCMV
      infection by secreting IFN-gamma.

PMID- 8139016
TI  - Expression and purification of the mouse mammary tumor virus gag-pro transframe
      protein p30 and characterization of its dUTPase activity.
AB  - The mouse mammary tumor virus gag-pro transframe protein (p30) contains the
      nucleocapsid protein domain derived from the 3' end of gag, fused to 154 residues
      encoded by the 5' region of the pro open reading frame. The DNA coding for p30
      was cloned into the plasmid pALTER-1, and an additional nucleotide was inserted
      by site-directed mutagenesis to allow the read-through from the gag into the pro
      open reading frame. The obtained insert was then cloned into pGEX-2T, a plasmid
      containing the glutathione S-transferase gene of Schistosoma japonicum and a
      nucleotide sequence encoding for a thrombin cleavage site. The chimeric protein
      (GST-p30) was isolated by affinity chromatography on a glutathione-Sepharose 4B
      column, and after thrombin treatment, the excised p30 was further purified on a
      single-stranded DNA-agarose column. This protein showed dUTPase activity, with
      only negligible cleavage of dATP, dGTP, dCTP, dTTP, or UTP. Its apparent Km for
      dUTP was 28 microM. The enzyme was inhibited by EDTA, but its effect could be
      reversed by Mg2+ and other divalent cations. dUTPase activity was also detected
      in purified mouse mammary tumor virus, and p30 was the only protein recognized by
      antibodies directed towards the carboxyl-terminal sequence of the dUTPase coding
      region.

PMID- 8139017
TI  - Effects of provirus integration in the Tpl-1/Ets-1 locus in Moloney murine
      leukemia virus-induced rat T-cell lymphomas: levels of expression,
      polyadenylation, transcriptional initiation, and differential splicing of the Ets
      1 mRNA.
AB  - The Tpl-1 locus was defined as a genomic DNA region which is targeted by provirus
      insertion during progression of Moloney murine leukemia virus-induced rat T-cell
      lymphomas. Using a panel of 156 (Mus musculus x Mus spretus) x Mus musculus
      interspecific backcross mice, we mapped Tpl-1 to mouse chromosome 9 at a distance
      of 1.2 +/- 0.9 centimorgans from the Ets-1 proto-oncogene (S.E. Bear, A.
      Bellacosa, P.A. Lazo, N.A. Jenkins, N.G. Copeland, C. Hanson, G. Levan, and P.N.
      Tsichlis, Proc. Natl. Acad. Sci. USA 86:7495-7499, 1989). In this report, we
      present evidence that all the known Tpl-1 provirus insertions occurred
      immediately 5' of the first exon of Ets-1 (exon A) and that the earlier detected
      distance between Tpl-1 and Ets-1 was due to the high frequency of meiotic
      recombination in the region between the site of provirus integration and exon
      III. Northern (RNA) blot analysis of polyadenylated RNA from normal adult rat
      tissues and Moloney murine leukemia virus-induced T-cell lymphomas and
      hybridization to a Tpl-1/Ets-1 probe derived from the 5' end of the gene revealed
      two lymphoid cell-specific RNA transcripts, of 5.5 and 2.2 kb. Sequence analysis
      of a near-full-length (4,991-bp) cDNA clone of the 5.5-kb RNA revealed a 441
      amino-acid open reading frame encoding a protein identical to the human and mouse
      Ets-1 proteins with the exception of five and nine species-specific conservative
      amino acid differences, respectively. The steady-state level of the Tpl-1/Ets-1
      RNA and of the Ets-1 protein was modestly elevated in tumors carrying a provirus
      in the Tpl-1 locus. The relative ratio of the two Ets-1 transcripts, which were
      shown to arise by differential polyadenylation, was not affected by provirus
      insertion. Moreover, the major site of transcriptional initiation, which was
      localized by primer extension 250 bp upstream of the 5' end of the Ets-1 cDNA
      clone, was shown to be identical in normal cells and tumors carrying a provirus
      in the Tpl-1 locus. Finally, the differential splicing of Ets-1 exon VII was
      shown by RNase protection to occur at a rate of 15 to 26% and to remain
      unaffected by provirus insertion. The subtlety of these effects, in contrast to
      the strong growth selection of cells with a provirus in the Tpl-1/Ets-1 locus,
      suggests that provirus insertion may affect the fine regulation of the gene,
      perhaps during cell cycle progression.

PMID- 8139018
TI  - Isolation and characterization of nonsense mutations in gene 10 of bacteriophage
      phi 6.
AB  - Nonsense mutants of bacteriophage phi 6 were isolated by a procedure that
      involved directed mutagenesis of a cDNA copy of genomic segment M, transcription
      of this segment, in vitro packaging into procapsids, and transfection of
      spheroplasts to form viable mutant phage. Recombinant phi 6 viruses that
      contained amber mutations in two open reading frames, ORF 10 and ORF D, of
      genomic segment M were isolated. We show that phi 6 protein P10 is the gene
      product of ORF 10. Further characterization of the phi 6 ORF 10(Am) mutant
      revealed that phi 6 membrane-associated protein P10 is not required to make
      enveloped phage particles in infected cells. Enveloped phage particles isolated
      from a phi 6 ORF 10(Am) infection contained extremely low levels of phi 6
      membrane-associated proteins P6 and P3. The low abundance is due to the very low
      level of P6 synthesis in phi 6 ORF 10(Am)-infected cells. The results suggest
      that P10 might play a role in regulating the translation of gene 6. Protein P10
      was found to be required for host lysis.

PMID- 8139019
TI  - Herpes simplex virus VP16 forms a complex with the virion host shutoff protein
      vhs.
AB  - Herpes simplex virus (HSV) virions contain at least two regulatory proteins that
      modulate gene expression in infected cells: the transcriptional activator VP16
      and the virion host shutoff protein vhs. VP16 stimulates transcription of the HSV
      immediate-early genes, and vhs suppresses host protein synthesis and induces
      accelerated turnover of cellular and viral mRNAs. We report here that vhs binds
      directly to VP16: vhs and VP16 were coprecipitated from infected cells by an anti
      vhs antiserum, and vhs and VP16 protein A fusions each bound intact versions of
      the other protein in a solid-phase capture assay. In addition, vhs and VP16
      interacted in the two-hybrid activator system when coexpressed in Saccharomyces
      cerevisiae. vhs residues 238 to 344 were sufficient for the interaction, and the
      VP16 acidic transcriptional activation domain was not required. vhs blocked the
      ability of VP16 to enter a multiprotein complex on an immediate-early TAATGARATTC
      consensus sequence, indicating that vhs interacts with one or more regions of
      VP16 required for promoter recognition. We suggest that this interaction may play
      a structural role in the assembly of HSV virions and modulate the activity of vhs
      during infection.

PMID- 8139020
TI  - Characterization of baculovirus-expressed herpes simplex virus type 1
      glycoprotein K.
AB  - The DNA region encoding the complete herpes simplex virus type 1 (HSV-1)
      glycoprotein K (gK) was inserted into a baculovirus transfer vector, and
      recombinant viruses expressing gK were isolated. Four gK-related recombinant
      baculovirus-expressed peptides of 29, 35, 38, and 40 kDa were detected with
      polyclonal antibody to gK. The 35-, 38-, and 40-kDa species were susceptible to
      tunicamycin treatment, suggesting that they were glycosylated. The 38- and 40-kDa
      species corresponded to partially glycosylated precursor gK (pgK) and mature gK,
      respectively. The 29-kDa peptide probably represented a cleaved, unglycosylated
      peptide. The 35-kDa peptide probably represented a cleaved, glycosylated peptide
      that may be a precursor to pgK. Indirect immunofluorescence with polyclonal
      antibody to gK peptides indicated that the recombinant baculovirus-expressed gK
      was abundant on the surface of the insect cells in which it was expressed. Mice
      vaccinated with the baculovirus-expressed gK produced very low levels (< 1:10) of
      HSV-1 neutralizing antibody. Nonetheless, these mice were partially protected
      from lethal challenge with HSV-1 (75% survival). This protection was significant
      (P = 0.02). Despite some protection against death, gK-vaccinated mice showed no
      protection against the establishment of latency. Surprisingly, gK-vaccinated mice
      that were challenged ocularly with a stromal disease-producing strain of HSV-1
      had significantly higher levels of ocular disease (herpes stromal keratitis) than
      did mock-vaccinated mice. In summary, this is the first report to show that
      vaccination with HSV-1 gK can provide protection against lethal HSV-1 challenge
      and that vaccination with an HSV-1 glycoprotein can significantly increase the
      severity of HSV-1-induced ocular disease.

PMID- 8139021
TI  - Simian virus 40 prevents activation of M-phase-promoting factor during lytic
      infection.
AB  - Simian virus 40 (SV40) infection stimulates confluent cultures of monkey kidney
      cells into successive rounds of cellular DNA synthesis without intervening
      mitosis. As an initial step in defining the mechanisms responsible for viral
      inhibition of mitosis, M-phase-promoting factor (MPF) was examined in SV40
      infected CV-1 cells passing from G2 phase into a second S phase. MPF is a serine
      threonine protein kinase that is essential for mitosis in eukaryotic cells. In
      SV40-infected cells exiting G2 phase, there was a reduced amount of MPF
      associated H1 kinase activity relative to that of uninfected cells passing
      through mitosis. Both subunits of MPF, cyclin B and the p34cdc2 catalytic
      subunit, were present and in a complex in infected cells. In uninfected cultures,
      passage through mitosis was associated with the dephosphorylation of the p34cdc2
      subunit, which is characteristic of MPF activation. In contrast, the p34cdc2
      subunit remained in the tyrosine-phosphorylated, inactive form in SV40-infected
      cells passing from G2 phase into a second S phase. These results suggest that
      although the MPF complex is assembled and modified normally, SV40 interferes with
      pathways leading to MPF activation.

PMID- 8139022
TI  - Immunopathogenic events in acute infection of rhesus monkeys with simian
      immunodeficiency virus of macaques.
AB  - Infection of the rhesus monkey with simian immunodeficiency virus of macaques
      (SIVmax) was employed to explore the early immune events associated with the
      initial containment of an acute AIDS virus infection. In nine rhesus monkeys
      infected intravenously with uncloned SIVmac strain 251, high-level p27 plasma
      antigenemia was usually detected transiently from approximately day 7 through day
      21 following virus inoculation. SIVmac replication in lymph nodes measured by in
      situ RNA hybridization closely paralleled the time course and magnitude of
      viremia. The containment of SIVmac spread by 3 to 4 weeks following infection
      suggests an efficient, early immune control of this virus infection. Anti-SIVmac
      antibodies were first detected in the blood at approximately day 14. At the time
      antigenemia was decreased or cleared, SIVmac neutralizing antibodies were
      present. A rise in circulating and lymph node CD8+ T cells also occurred
      coincident with the clearance of antigenemia and persisted thereafter. These CD8+
      lymphocytes in lymph nodes had increased expression of both major
      histocompatibility complex class II and the adhesion molecule LFA-1; they also
      demonstrated decreased expression of the naive T-cell-associated CD45RA molecule.
      SIVmac-specific cytotoxic T-lymphocyte precursors were detected in both blood and
      lymph node by 7 days post-virus inoculation. These studies indicate that both
      virus-specific humoral and cellular immune mechanisms in blood and lymph node are
      associated with the clearance of viremia that occurs within the first month of
      infection of rhesus monkeys with SIVmac.

PMID- 8139023
TI  - In vivo evolution of c-rel oncogenic potential.
AB  - The c-rel proto-oncogene belongs to the NF-kappa B/rel and I kappa B gene
      families, which regulate several inducible processes, including self
      defense/repair and embryogenesis. Transduction of the c-rel transcription factor
      by the avian retrovirus resulted in the formation of a highly oncogenic virus,
      reticuloendotheliosis virus strain T (REV-T), that encodes the oncogene v-rel. To
      examine the oncogenic potential of c-rel, we inserted it into a REV-T-based
      retroviral vector, rescued virus [REV-C(CSV)], and infected 1-day-old chicks. All
      birds developed tumors, and all cell lines established from REV-C-induced tumors
      expressed c-rel proteins that lacked C-terminal sequences. These proteins,
      responsible for both in vivo and in vitro cell proliferation, were apparently
      selected for their oncogenic potential. In order to examine the cooperation of C
      terminal deletions with other oncogenic alterations in vivo, point mutations
      present in the N-terminal and middle regions of v-rel were analyzed by a similar
      protocol. The data obtained support four conclusions. (i) c-rel proteins bearing
      any of three single-amino-acid mutations present in the N-terminal portion of v
      rel were sufficiently oncogenic to induce tumor development in the absence of
      additional mutations. (ii) Combining a mutation from the N-terminal region of v
      rel with a deletion of the C-terminal sequences of c-rel increases the
      oncogenicity of the protein in an additive manner. (iii) Mutations present in the
      middle of v-rel cooperated synergistically with C-terminal deletions to produce
      highly transforming viruses. (iv) Deletion of c-rel produced a variety of
      transforming rel proteins with sizes that extended from 42 to 65 kDa. The most
      frequently isolated rel deletion was 62 kDa in size. To examine the basis for the
      selection of different rel mutants, their ability to induce immunoregulatory
      surface receptors was analyzed. The data revealed a correlation between the
      induction capacity of these mutants and their corresponding contribution to in
      vivo tumorigenic potential. Moreover, an analysis of the subcellular localization
      of different rel proteins revealed an inverse correlation between the size of the
      protein and the proportion in the nucleus of lymphoid cells.

PMID- 8139024
TI  - Activation of cerebral cytokine gene expression and its correlation with onset of
      reactive astrocyte and acute-phase response gene expression in scrapie.
AB  - The pathogenesis of scrapie, a transmissible subacute spongiform encephalopathy,
      is unclear. However, certain aspects of the known cellular and molecular
      neuropathology in scrapie led us to hypothesize that cytokines could mediate
      cerebral pathological changes in this neurodegenerative disease. Therefore,
      expression of multiple cytokine genes in the brain and peripheral organs of
      scrapie-infected mice was examined. Late in the course of scrapie, expression of
      tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and IL
      1 beta mRNA was markedly increased in the brain but not the spleen, kidneys, or
      liver. In time course studies, scrapie-infected mice exhibited increased cerebral
      expression of the TNF-alpha, IL-1 alpha, and IL-1 beta mRNAs by week 15
      postinoculation--a time point that coincided with the onset of clinical symptoms.
      Thereafter, the levels of these cytokine transcripts increased progressively to
      the terminal stages of of the disease (week 25). To determine the relationship of
      the increased cerebral expression of the cytokine mRNAs to the development of
      pathological changes in scrapie, we examined the expression of the glial
      fibrillary acidic protein gene (a marker for astrocytosis) and the murine acute
      phase response gene homologous to the alpha 1-antichymotrypsin gene (designated
      EB22/5.3). Markedly increased expression of both the glial fibrillary acidic
      protein and EB22/5.3 mRNAs was observed in the brain but not the peripheral
      organs of scrapie-infected mice. The increased expression of both these gene
      products also occurred at week 15 of infection and, thereafter, increased
      progressively to the terminal stages of the disease. Therefore, infection of mice
      with scrapie resulted in significant increases in the expression of the TNF
      alpha, IL-1 alpha, and IL-1 beta gene products, whose pattern correlated with the
      onset and development of molecular and clinical pathological changes. Since
      scrapie is known not to evoke an immune response, the present findings strongly
      suggest the existence of a localized cerebral host response to the agent during
      which proinflammatory cytokines could be key pathogenic mediators.

PMID- 8139025
TI  - The tobacco etch potyvirus 6-kilodalton protein is membrane associated and
      involved in viral replication.
AB  - The tobacco etch potyvirus (TEV) genome encodes a polyprotein that is processed
      by three virus-encoded proteinases. Although replication of TEV likely occurs in
      the cytoplasm, two replication-associated proteins, VPg-proteinase (nuclear
      inclusion protein a) (NIa) and RNA-dependent RNA polymerase (nuclear inclusion
      protein b) (NIb), accumulate in the nucleus of infected cells. The 6-kDa protein
      is located adjacent to the N terminus of NIa in the TEV polyprotein, and, in the
      context of a 6-kDa protein/NIa (6/NIa) polyprotein, impedes nuclear translocation
      of NIa (M. A. Restrepo-Hartwig and J. C. Carrington, J. Virol. 66:5662-5666,
      1992). The 6-kDa protein and three polyproteins containing the 6-kDa protein were
      identified by affinity chromatography of extracts from infected plants. Two of
      the polyproteins contained NIa or the N-terminal VPg domain of NIa linked to the
      6-kDa protein. To investigate the role of the 6-kDa protein in vivo, insertion
      and substitution mutagenesis was targeted to sequences coding for the 6-kDa
      protein and its N- and C-terminal cleavage sites. These mutations were introduced
      into a TEV genome engineered to express the reporter protein beta-glucuronidase
      (GUS), allowing quantitation of virus amplification by a fluorometric assay.
      Three-amino-acid insertions at each of three positions in the 6-kDa protein
      resulted in viruses that were nonviable in tobacco protoplasts. Disruption of the
      N-terminal cleavage site resulted in a virus that was approximately 10% as active
      as the parent, while disruption of the C-terminal processing site eliminated
      virus viability. The subcellular localization properties of the 6-kDa protein
      were investigated by fractionation and immunolocalization of 6-kDa protein/GUS
      (6/GUS) fusion proteins in transgenic plants. Nonfused GUS was associated with
      the cytosolic fraction (30,000 x g centrifugation supernatant), while 6/GUS and
      GUS/6 fusion proteins sedimented with the crude membrane fraction (30,000 x g
      centrifugation pellet). The GUS/6 fusion protein was localized to apparent
      membranous proliferations associated with the periphery of the nucleus. These
      data suggest that the 6-kDa protein is membrane associated and is necessary for
      virus replication.

PMID- 8139026
TI  - A steroid hormone response unit in the late leader of the noncoding control
      region of the human polyomavirus BK confers enhanced host cell permissivity.
AB  - The effect of steroid hormones on multiplication of the human polyomavirus BK
      (BKV) was studied. Physiological concentrations of the synthetic glucocorticoid
      dexamethasone, progesterone R5020, or estrogen 17 beta-estradiol enhanced the
      permissivity of the host cell for BKV, resulting in an up to 11-fold
      (dexamethasone), 5-fold (progesterone), or 3-fold (17 beta-estradiol) higher
      virus yield. The increase in virus yield in dexamethasone-stimulated cells
      correlated with enhanced steady-state levels of viral transcripts. The late
      leader sequence of the BKV control region contains a hormone response unit
      composed of a nonconsensus glucocorticoid and/or progesterone response element
      (GRE/PRE) and a fully consensus estrogen response element (ERE). DNA-protein
      binding studies showed that the glucocorticoid receptor and the progesterone
      receptor bound to this BKV GRE/PRE-like sequence, while the estrogen receptor
      could bind to the BKV ERE motif. By transient transfection assays, we were able
      to show that these sequences can mediate steroid hormone-induced gene expression.
      However, no cooperative transactivation effect between the BKV GRE/PRE-like motif
      and BKV ERE motif was observed. This BKV hormone response unit may play an
      important role in vivo by enhancing a productive BKV infection, and perhaps also
      by reactivating a latent infection, during physiological or pathological
      conditions accompanied by increased steroid hormone levels.

PMID- 8139027
TI  - Hepatitis B virus surface antigen binds to apolipoprotein H.
AB  - We have previously demonstrated that a plasma membrane-enriched fraction isolated
      from human liver is capable of binding recombinant hepatitis B surface antigen
      (rHBsAg) (P. Pontisso, M. A. Petit, M. Bankowski, and M. E. Peeples, J. Virol.
      63:1981-1988, 1989). In this study we have separated the plasma membrane proteins
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and used a ligand
      blotting technique to identify a 46-kDa rHBsAg-binding protein. This protein
      could be removed from the membranes with a weakly acidic buffer, implying that it
      is peripherally bound. Examination of human serum revealed that the 46-kDa
      binding protein is a serum protein. Isolation of plasma lipoproteins revealed
      that the binding protein is in part associated with chylomicrons and high-density
      lipoproteins, both of which are targeted to the hepatocyte during the normal
      course of lipid metabolism. The binding protein was identified as apolipoprotein
      H (apo H), also known as beta 2-glycoprotein I, on the basis of copurification of
      the rHBsAg-binding activity with the apo H protein and the ability of cDNA
      expressed apo H to bind rHBsAg. Serum-derived HBsAg also binds to apo H,
      indicating that binding is not unique to rHBsAg. Binding is saturable, requires
      only the small S protein of rHBsAg, and is inhibited by excess rHBsAg, antibodies
      to HBsAg, and antibodies to apo H. The binding activity of apo H is destroyed
      upon reduction, indicating that 1 or more of its 22 disulfide bonds are required
      for interaction with rHBsAg. The possibility that an interaction between
      hepatitis B virus particles and lipoprotein particles may facilitate entry of the
      virus into hepatocytes is discussed.

PMID- 8139028
TI  - Two functional domains of the influenza virus NS1 protein are required for
      regulation of nuclear export of mRNA.
AB  - The influenza virus NS1 protein is the only known example of a protein that
      inhibits the nuclear export of mRNA. To identify the functional domains of this
      protein, we introduced 18 2- or 3-amino-acid substitutions at approximately
      equally spaced locations along the entire length of the protein. Two functional
      domains were identified. The domain near the amino end (amino acids 19 through
      38) was shown to be the RNA-binding domain, by using a gel shift assay with
      purified NS1 protein and spliced viral NS2 mRNA as the RNA target. The second
      domain, which is in the carboxy half of the molecule, was presumed to be the
      effector domain that interacts with host nuclear proteins to carry out the
      nuclear RNA export function, by analogy with the effector domain of the Rev
      proteins of human immunodeficiency virus (HIV) and other lentiviruses which
      facilitate rather than inhibit nuclear RNA export. The NS1 protein has a 10-amino
      acid sequence that is similar to the consensus sequence in the effector domains
      of lentivirus Rev proteins, specifically including two crucial leucines at
      positions 7 and 9 of this sequence. However, the effector domains of the NS1 and
      Rev (HIV type 1 [HIV-1]) proteins differed in several significant ways including
      the following: (i) unlike the HIV-1 Rev protein, NS1 effector domain mutants were
      negative recessive rather than negative dominant, (ii) the NS1 effector domain is
      about three times larger than the effector domain of the HIV-1 Rev protein, and
      (iii) unlike the HIV-1 protein, NS1 effector domain mutants exhibited a
      surprising property, a changed intracellular/intranuclear distribution, compared
      with the wild-type protein. These differences strongly suggest that the effector
      domains of the NS1 and Rev proteins interact with different nuclear protein
      targets, which likely explains the opposite effects of these two proteins on
      nuclear mRNA export.

PMID- 8139029
TI  - Assembly of herpes simplex virus (HSV) intermediate capsids in insect cells
      infected with recombinant baculoviruses expressing HSV capsid proteins.
AB  - The capsid of herpes simplex virus type 1 (HSV-1) is composed of seven proteins,
      VP5, VP19C, VP21, VP22a, VP23, VP24, and VP26, which are the products of six HSV
      1 genes. Recombinant baculoviruses were used to express the six capsid genes
      (UL18, UL19, UL26, UL26.5, UL35, and UL38) in insect cells. All constructs
      expressed the appropriate-size HSV proteins, and insect cells infected with a
      mixture of the six recombinant baculoviruses contained large numbers of HSV-like
      capsids. Capsids were purified by sucrose gradient centrifugation, and electron
      microscopy showed that the capsids made in Sf9 cells had the same size and
      appearance as authentic HSV B capsids. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis demonstrated that the protein composition of these
      capsids was nearly identical to that of B capsids isolated from HSV-infected Vero
      cells. Electron microscopy of thin sections clearly demonstrated that the capsids
      made in insect cells contained the inner electron-translucent core associated
      with HSV B capsids. In infections in which single capsid genes were left out, it
      was found that the UL18 (VP23), UL19 (VP5), UL38 (VP19C), and either the UL26
      (VP21 and VP24) or the UL26.5 (VP22a) genes were required for assembly of 100-nm
      capsids. VP22a was shown to form the inner core of the B capsid, since in
      infections in which the UL26.5 gene was omitted the 100-nm capsids that formed
      lacked the inner core. The UL35 (VP26) gene was not required for assembly of 100
      nm capsids, although assembly of B capsids was more efficient when it was
      present. These and other observations indicate that (i) the products of the UL18,
      UL19, UL35, and UL38 genes self-assemble into structures that form the outer
      surface (icosahedral shell) of the capsid, (ii) the products of the UL26 and/or
      UL26.5 genes are required (as scaffolds) for assembly of 100-nm capsids, and
      (iii) the interaction of the outer surface of the capsid with the scaffolding
      proteins requires the product of the UL18 gene (VP23).

PMID- 8139030
TI  - Evolution of feline leukemia virus variant genomes with insertions, deletions,
      and defective envelope genes in infected cats with tumors.
AB  - In order to study retroviral variation, selection, and viral correlates of in
      vivo pathogenicity, we documented the evolution of feline leukemia virus (FeLV)
      variants in cats that died with thymic lymphoma after infection with molecularly
      cloned subgroup A FeLV. Using genomic DNA from cat necropsy samples, we employed
      PCR to amplify and clone the envelope gene, which is a major determinant of the
      specific pathogenicity of different FeLV variants. In the envelope gene,
      mutations encoded scattered amino acid changes that did not cluster into clearly
      definable variable regions; however, characterization of these terminal variant
      sequences revealed a predominance of G-to-A and A-to-G nucleotide substitutions.
      Additionally, some cats harbored variants with recombinant subgroup B-like
      envelope genes, while the major variant from one cat had a 12-bp insertion in a
      region previously characterized as an immunodeficiency-inducing determinant.
      Finally, proviruses from tumor DNA frequently possessed envelope genes predicted
      to encode a protein truncated in the N-terminal half because of either premature
      termination codons or deletions ranging from 29 to 1,666 bp. In contrast, all
      envelope genes cloned from the bone marrow of one cat were predicted to encode
      full-length envelope product, and only a minority of proviral clones from a cat
      that did not develop a tumor had defective envelope genes. Thus, in the cat,
      viruses evolved from subgroup A FeLV that had point mutations, insertions,
      deletions, or recombinant envelope genes. Furthermore, defective variants were
      particularly prominent in T-cell tumors.

PMID- 8139031
TI  - Varicella-zoster virus open reading frame 4 encodes a transcriptional activator
      that is functionally distinct from that of herpes simplex virus homology ICP27.
AB  - Varicella-zoster virus is the etiological agent of chickenpox and zoster in
      humans and belongs to the Alphaherpesvirinae subfamily within the family
      Herpesviridae. Much of the current understanding of gene regulation in
      alphaherpesviruses has been derived from studies of the prototype herpes simplex
      virus (HSV). In HSV, two virus-encoded, trans-regulatory proteins, ICP4 and
      ICP27, are essential for the replicative cycle of the virus. ICP4 is important in
      modulating HSV genes of all three kinetic classes, whereas the trans-regulatory
      effects of ICP27 are primarily associated with the expression of late genes.
      Recent evidence indicates that the trans-regulatory effects of ICP27 involve
      posttranscriptional processing of target gene transcripts (R. M. Sandri-Golding
      and G. E. Mendoza, Genes Dev. 6:848-863, 1992). The ICP27 homolog in varicella
      zoster virus is a 452-amino-acid polypeptide encoded by the open reading frame 4
      (ORF4) gene. Contrary to what is found with ICP27, we show that the ORF4
      polypeptide is a transcriptional activator of diverse target promoters and has a
      critical requirement for the presence of upstream elements within these promoters
      to mediate its transcriptional effects. Evidence is also presented to implicate a
      critical role for the cysteine-rich, C-terminal region of the ORF4 polypeptide in
      its trans-regulatory functions. Specifically, by oligonucleotide-directed site
      specific mutagenesis, we demonstrate that of 10 cysteine residues in the ORF4
      polypeptide, only C-421 and C-426 are essential for transactivator function and
      suggest that these cysteine residues may participate in critical protein-protein
      interactions rather than protein-nucleic acid interactions to mediate ORF4
      inducibility.

PMID- 8139032
TI  - Evidence for a functional interaction between the V1/V2 and C4 domains of human
      immunodeficiency virus type 1 envelope glycoprotein gp120.
AB  - The domains of the human immunodeficiency virus type 1 (HIV-1) envelope
      glycoprotein that are required for envelope function have been partially
      characterized. Little is known, however, about the nature of the interactions
      between these domains. To identify regions of the HIV-1 envelope glycoprotein
      that are involved in interactions necessary for proper envelope function, we
      constructed a series of 14 envelope recombinants between the env genes of two HIV
      1 isolates. The envelope chimeras were examined for their ability to induce
      syncytia, to be proteolytically processed, and to function during a spreading
      viral infection. Our results demonstrate that the exchange between the two
      isolates of the first and second hypervariable regions (V1/V2) of gp120 results
      in defects in envelope glycoprotein processing, syncytium formation, and
      infectivity. Long-term passage of cultures infected with virus bearing a V1/V2
      chimeric envelope glycoprotein leads to the emergence of a revertant virus with
      replication characteristics comparable to those of the wild type. Analysis of the
      revertant indicated that an Ile-->Met change in the C4 region of gp120 (between
      hypervariable regions V4 and V5) is responsible for the revertant phenotype. This
      single amino acid change restores infectivity without significantly affecting
      gp160 processing, CD4 binding, or the levels of virion-associated gp120. While
      the Ile-->Met change in C4 greatly enhances the fusogenic potential of the V1/V2
      chimeric envelope glycoprotein, it has a detrimental effect on syncytium
      formation when analyzed in the context of the wild-type envelope. These results
      suggest that an interaction required for proper envelope glycoprotein function
      occurs between the V1/V2 and C4 regions of gp120.

PMID- 8139033
TI  - Expression of the TM protein of Rous sarcoma virus in the absence of SU shows
      that this domain is capable of oligomerization and intracellular transport.
AB  - The SU and TM subunits of the Rous sarcoma virus glycoprotein, which are derived
      from a single polypeptide precursor, have been expressed independently with a
      simian virus 40 vector. The TM protein retains the ability to form an oligomer
      which resembles the TM oligomer derived from the wild-type glycoprotein complex
      present in virions. Oligomerization of the recombinant TM protein is more rapid
      than that observed for the intact glycoprotein expressed from the simian virus 40
      vector and is required for its transport out of the endoplasmic reticulum.
      Oligomeric TM is terminally glycosylated in the Golgi complex but is less stable
      than the intact wild-type protein and does not accumulate at the cell surface.
      The SU protein, in contrast, does not form detectable oligomers but is
      efficiently secreted into the culture medium. These observations suggest that the
      oligomerization domain of the Rous sarcoma virus glycoprotein lies in the TM
      protein and that it can function independently of SU.

PMID- 8139034
TI  - An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a
      polypeptide with Cys/His sequence motifs.
AB  - Two different baculovirus genes are known to be able to block apoptosis triggered
      upon infection of Spodoptera frugiperda cells with p35 mutants of the insect
      baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV):p35 (P35
      encoding gene) of AcMNPV (R. J. Clem, M. Fechheimer, and L. K. Miller, Science
      254:1388-1390, 1991) and iap (inhibitor of apoptosis gene) of Cydia pomonella
      granulosis virus (CpGV) (N. E. Crook, R. J. Clem, and L. K. Miller, J. Virol.
      67:2168-2174, 1993). Using a genetic complementation assay to identify additional
      genes which inhibit apoptosis during infection with a p35 mutant, we have
      isolated a gene from Orgyia pseudotsugata NPV (OpMNPV) that was able to
      functionally substitute for AcMNPV p35. The nucleotide sequence of this gene, Op
      iap, predicted a 30-kDa polypeptide product with approximately 58% amino acid
      sequence identity to the product of CpGV iap, Cp-IAP. Like Cp-IAP, the predicted
      product of Op-iap has a carboxy-terminal C3HC4 zinc finger-like motif. In
      addition, a pair of additional cysteine/histidine motifs were found in the N
      terminal regions of both polypeptide sequences. Recombinant p35 mutant viruses
      carrying either Op-iap or Cp-iap appeared to have a normal phenotype in S.
      frugiperda cells. Thus, Cp-IAP and Op-IAP appear to be functionally analogous to
      P35 but are likely to block apoptosis by a different mechanism which may involve
      direct interaction with DNA.

PMID- 8139035
TI  - Identification of a membrane-binding domain within the amino-terminal region of
      human immunodeficiency virus type 1 Gag protein which interacts with acidic
      phospholipids.
AB  - Retroviral Gag proteins are targeted to the plasma membrane, where they play the
      central role in virion formation. Several studies have suggested that the
      membrane-binding signal is contained within the amino-terminal matrix sequence;
      however, the precise location has never been determined for the Gag protein of
      any retrovirus. In this report, we show that the first 31 residues of human
      immunodeficiency virus type 1 Gag protein can function independently as a
      membrane-targeting domain when fused to heterologous proteins. A bipartite
      membrane-targeting motif was identified, consisting of the myristylated N
      terminal 14 amino acids and a highly basic region that binds acidic
      phospholipids. Replacement of the N-terminal membrane-targeting domain of pp60v
      src with that of human immunodeficiency virus type 1 Gag elicits efficient
      membrane binding and a transforming phenotype. Removal of myristate or the basic
      region results in decreased membrane binding of Gag-Src chimeras in vitro and
      impaired virion formation by Pr55gag in vivo. We propose that the N-terminal Gag
      sequence functions as a targeting signal to direct interaction with acidic
      phospholipids on the cytoplasmic leaflet of the plasma membrane.

PMID- 8139036
TI  - Differences in CD4 dependence for infectivity of laboratory-adapted and primary
      patient isolates of human immunodeficiency virus type 1.
AB  - CD4 is known to be an important receptor for human immunodeficiency virus type 1
      (HIV-1) infection of T lymphocytes and macrophages. However, the limiting steps
      in CD4-dependent HIV-1 infections in vivo and in vitro are poorly understood. To
      address this issue, we produced a panel of HeLa-CD4 cell clones that express
      widely different amounts of CD4 and quantitatively analyzed their infection by
      laboratory-adapted and primary patient HIV-1 isolates. For all HIV-1 isolates,
      adsorption from the medium onto HeLa-CD4 cells was inefficient and appeared to be
      limiting for infection in the conditions of our assays. Adsorption of HIV-1 onto
      CD4-positive peripheral blood mononuclear cells was also inefficient. Moreover,
      there was a striking difference between laboratory-adapted and primary T-cell
      tropic HIV-1 isolates in the infectivity titers detected on different HeLa-CD4
      cells. Laboratory-adapted HIV-1 isolates infected all HeLa-CD4 cell clones with
      equal efficiencies regardless of the levels of CD4, whereas primary HIV-1
      isolates infected these clones in direct proportion to cellular CD4 expression.
      Our interpretation is that for laboratory-adapted isolates, a barrier step that
      preceeds CD4 encounter was limiting and the subsequent CD4-dependent virus
      capture process was highly efficient, even at very low cell surface
      concentrations. In contrast, for primary HIV-1 isolates, the CD4-dependent steps
      appeared to be much less efficient. We conclude that primary isolates of HIV-1
      infect inefficiently following contact with surfaces of CD4-positive cells, and
      we propose that this confers a selective disadvantage during passage in rapidly
      dividing leukemia cell lines. Conversely, in vivo selective pressure appears to
      favor HIV-1 strains that require large amounts of CD4 for infection.

PMID- 8139037
TI  - Homolog-scanning mutagenesis reveals poliovirus receptor residues important for
      virus binding and replication.
AB  - Poliovirus initiates infection of primate cells by binding to the poliovirus
      receptor, Pvr. Mouse cells do not bind poliovirus but express a Pvr homolog, Mph,
      that does not function as a poliovirus receptor. Previous work has shown that the
      first immunoglobulin-like domain of the Pvr protein contains the virus binding
      site. To further identify sequences of Pvr important for its interaction with
      poliovirus, stable cell lines expressing mutated Pvr molecules were examined for
      their abilities to bind virus and support virus replication. Substitution of the
      amino-terminal domain of Mph with that of Pvr yields a molecule that can function
      as a poliovirus receptor. Cells expressing this chimeric receptor have normal
      binding affinity for poliovirus, yet the kinetics of virus replication are
      delayed. Results of virus alteration assays indicate that this chimeric receptor
      is defective in converting native virus to 135S altered particles. This defect is
      not observed with cells expressing receptor recombinants that include Pvr domains
      1 and 2. Because altered particles are believed to be an intermediate in
      poliovirus entry, these findings suggest that Pvr domains 2 and 3 participate in
      early stages of infection. Additional mutants were made by substituting variant
      Mph residues for the corresponding residues in Pvr. The results were interpreted
      by using a model of Pvr predicted from the known structures of other
      immunoglobulin-like V-type domains. Analysis of stable cell lines expressing the
      mutant proteins revealed that virus binding is influenced by mutations in the
      predicted C'-C" loop, the C" beta-strand, the C"-D loop, and the D-E loop.
      Mutations in homologous regions of the immunoglobulin-like CD4 molecule alter its
      interaction with gp120 of human immunodeficiency virus type 1. Cells expressing
      Pvr mutations on the predicted C" edge do not develop cytopathic effect during
      poliovirus infection, suggesting that poliovirus-induced cytopathic effect may be
      induced by the virus-receptor interaction.

PMID- 8139038
TI  - Temporal regulation of a complex and unconventional promoter by viral products.
AB  - The DNA polymerase (dnapol) gene of Autographa californica nuclear polyhedrosis
      virus presents a complex promoter organization. It lacks the usual TATA box and
      start site, and its RNA accumulation initially increases and then decreases
      dramatically during infection. We investigated dnapol temporal regulation.
      Transiently expressed dnapol gene was transcribed at a low level from minor start
      sites. Coexpression with ie0 and/or ie1 immediate-early genes dramatically
      enhanced dnapol transcription, specifically from a new start site. Moreover, the
      ie1 transactivation required little or no information in front of this
      nonconventional proximal promoter. We showed that IE0 and IE1 proteins were
      stably expressed during infection and that the dnapol mRNA level decrease was not
      a consequence of the disappearance of these proteins. The dnapol promoter region
      contains a putative overlapping open reading frame (ORF) in the opposite
      direction. We showed that ORF-2 was indeed highly expressed late, when the dnapol
      mRNA level decreased, and that during that time, dnapol mRNA stability was not
      significantly altered, excluding a destabilizing antisense effect. Additionally,
      we showed that the dnapol promoter was inhibited late but not early during the
      infection of cells transiently expressing constructs carrying either the intact
      or the altered ORF-2 promoter. Therefore, ORF-2 initiation of transcription and
      dnapol promoter inhibition are two coincidental nonrelated phenomena. Finally, we
      showed that both IE1 transactivation and late inhibition occurred in the same
      limited region around the dnapol promoter.

PMID- 8139039
TI  - Temperature-sensitive mutations in the gene encoding the small subunit of the
      vaccinia virus early transcription factor impair promoter binding, transcription
      activation, and packaging of multiple virion components.
AB  - The vaccinia virus D6R open reading frame encodes the small subunit of the
      heterodimeric vaccinia virus early transcription factor (VETF) that activates
      transcription of early genes in vitro. VETF binds early gene promoters and has a
      DNA-dependent ATPase activity that is essential for activation of transcription.
      To examine the relationship between the structure and function of VETF, we have
      localized the mutations in two temperature-sensitive viruses whose lesions
      previously were mapped to the D6R gene. For both mutants, a single G-to-A
      nucleotide change that would alter protein coding potential was identified. In
      mutant E93, the codon for alanine 25 was changed to that of threonine, and in
      mutant S4 the codon for valine 278 was replaced with that for methionine. The
      molecular phenotype of each mutant was assessed by expressing mutant
      transcription factors in HeLa cells by using a vaccinia virus-T7 system and
      characterizing the proteins' activities in vitro. The A25T mutant activated
      transcription to a lesser extent than wild-type VETF, and the V278M mutant had no
      demonstrable transcription factor activity. Both mutant proteins were shown to be
      defective for promoter binding, accounting for their impairment in transcription
      activation. The functional defects for both mutants were observed at permissive
      as well as nonpermissive temperatures. The mutant proteins retained ATPase
      activity but required higher DNA concentrations to activate the ATPase. These
      results indicate that the small subunit of VETF is essential for its promoter
      binding activity and likely contacts the promoter DNA. Immunoblotting experiments
      showed that the virion particles from the two mutant viruses contained about half
      the VETF of wild-type virus, suggesting that promoter binding may contribute to
      packaging of VETF into the virion particle. RNA polymerase, mRNA capping enzyme,
      and nucleoside triphosphate phosphohydrolase I were found at similarly reduced
      levels in the virion, indicating that packaging of some virion core enzymes may
      be interdependent.

PMID- 8139040
TI  - Evidence for coronavirus discontinuous transcription.
AB  - Coronavirus subgenomic mRNA possesses a 5'-end leader sequence which is derived
      from the 5' end of genomic RNA and is linked to the mRNA body sequence. This
      study examined whether coronavirus transcription involves a discontinuous
      transcription step; the possibility that a leader sequence from mouse hepatitis
      virus (MHV) genomic RNA could be used for MHV subgenomic defective interfering
      (DI) RNA transcription was examined. This was tested by using helper viruses and
      DI RNAs that were easily distinguishable. MHV JHM variant JHM(2), which
      synthesizes a subgenomic mRNA encoding the HE gene, and variant JHM(3-9), which
      does not synthesize this mRNA, were used. An MHV DI RNA, DI(J3-9), was
      constructed to contain a JHM(3-9)-derived leader sequence and an inserted
      intergenic region derived from the region preceding the MHV JHM HE gene. DI(J3-9)
      replicated efficiently in JHM(2)- or JHM(3-9)-infected cells, whereas synthesis
      of subgenomic DI RNAs was observed only in JHM(2)-infected cells. Sequence
      analyses demonstrated that the 5' regions of both helper virus genomic RNAs and
      genomic DI RNAs maintained their original sequences in DI RNA-replicating cells,
      indicating that the genomic leader sequences derived from JHM(2) functioned for
      subgenomic DI RNA transcription. Replication and transcription of DI(J3-9) were
      observed in cells infected with an MHV A59 strain whose leader sequence was
      similar to that of JHM(2), except for one nucleotide substitution within the
      leader sequence. The 5' region of the helper virus genomic RNA and that of the DI
      RNA were the same as their original structures in virus-infected cells, and the
      leader sequence of DI(J3-9) subgenomic DI RNA contained the MHV A59-derived
      leader sequence. The leader sequence of subgenomic DI RNA was derived from that
      of helper virus; therefore, the genomic leader sequence had a trans-acting
      property indicative of a discontinuous step in coronavirus transcription.

PMID- 8139041
TI  - A transcriptional regulatory element is associated with a nuclease-hypersensitive
      site in the pol gene of human immunodeficiency virus type 1.
AB  - Analysis of the chromatin organization of the integrated human immunodeficiency
      virus type 1 (HIV-1) genome has previously revealed a major constitutive DNase I
      hypersensitive site associated with the pol gene (E. Verdin, J. Virol. 65:6790
      6799, 1991). In the present report, high-resolution mapping of this site with
      DNase I and micrococcal nuclease identified a nucleosome-free region centered
      around nucleotides (nt) 4490 to 4766. A 500-bp fragment encompassing this
      hypersensitive site (nt 4481 to 4982) exhibited transcription-enhancing activity
      (two- to threefold) when it was cloned in its natural position with respect to
      the HIV-1 promoter after transient transfection in U937 and CEM cells. Using in
      vitro footprinting and gel shift assays, we have identified four distinct binding
      sites for nuclear proteins within this positive regulatory element. Site B (nt
      4519 to 4545) specifically bound four distinct nuclear protein complexes: a
      ubiquitous factor, a T-cell-specific factor, a B-cell-specific factor, and the
      monocyte/macrophage- and B-cell-specific transcription factor PU.1/Spi-1. In most
      HIV-1 isolates in which this PU box was not conserved, it was replaced by a
      binding site for the related factor Ets1. Factors binding to site C (nt 4681 to
      4701) had a DNA-binding specificity similar to that of factors binding to site B,
      except for PU.1/Spi-1. A GC box containing a binding site for Sp1 was identified
      (nt 4623 to 4631). Site D (nt 4816 to 4851) specifically bound a ubiquitously
      expressed factor. These results identify a transcriptional regulatory element
      associated with a nuclease-hypersensitive site in the pol gene of HIV-1 and
      suggest that its activity may be controlled by a complex interplay of cis
      regulatory elements.

PMID- 8139042
TI  - Spontaneous substitutions in the vicinity of the V3 analog affect cell tropism
      and pathogenicity of simian immunodeficiency virus.
AB  - Simian immunodeficiency virus (SIV) exists within tissues of infected macaques as
      a mixture of diverse genotypes. The goal of this study was to investigate the
      biologic significance of this variation in terms of cellular tropism and
      pathogenicity. PCR was used to amplify and clone 3'-half genomes from the spleen
      of an immunodeficiency SIV-infected pig-tailed macaque (Macaca nemestrina). Eight
      infectious clones were generated by ligation of respective 3' clones into a
      related SIVsm 5' clone, and virus stocks were generated by transient
      transfection. Four of these viruses were infectious for macaque peripheral blood
      mononuclear cells (PBMC) or monocyte-derived macrophages (MDM). Three viruses
      with distinct tropism for macaque PBMC or MDM were tested for in vivo infectivity
      and pathogenicity. The ability of these three viruses to infect PBMC and
      macrophages correlated with differences in infectivity and pathogenicity. Thus, a
      virus that was infectious for both PBMC and MDM was highly infectious for
      macaques and induced AIDS in half of the inoculated animals. In contrast, virus
      that was less infectious for PBMC and not infectious for MDM induced only
      transient viremia. Finally, a virus that was not infectious for either primary
      cell type did not infect macaques. Chimeric clones exchanging portions of the
      envelope gene of the 62A and smH4 molecular clones and a series of point mutants
      were used to map the determinant of tropism to a 60-amino-acid region of gp120
      encompassing the V3 analog of SIV. Naturally occurring mutations within this
      region were critical for determining tropism and, as a result, pathogenicity of
      these SIVsm clones.

PMID- 8139043
TI  - Negative regulation of the 5' long terminal repeat (LTR) by the 3' LTR in the
      murine proviral genome.
AB  - To assess the influence of the 3' long terminal repeat (LTR) on the
      promoter/enhancer activity of the 5' LTR, a set of isogenic retroviral vectors
      differing only in the U3 region of the 3' LTR was constructed. These U3 elements
      were derived from viruses with different tissue tropism. The 5' LTR originated
      from Moloney murine leukemia virus and directed the transcription of a reporter
      gene (chloramphenicol acetyltransferase [CAT] gene), giving rise to plasmids of
      the general configuration LTR-CAT-LTR'. Following transfection of these chimeric
      constructs into various cell types, the CAT activity in a given cell line was
      inversely related to the activity of the downstream U3 region when used in a
      single-LTR construct in that cell type, indicating negative regulation of the 5'
      LTR by the chimeric 3' LTR'. Our data indicate that a highly active 3' LTR
      interferes with gene expression from the 5' LTR. Potential mechanisms for this
      down-regulation are discussed.

PMID- 8139044
TI  - Naturally occurring escape mutants of hepatitis B virus with various mutations in
      the S gene in carriers seropositive for antibody to hepatitis B surface antigen.
AB  - Hepatitis B virus (HBV) DNA was extracted from sera of six carriers with
      hepatitis B e antigen as well as antibody to hepatitis B surface antigen and
      sequenced within the pre-S regions and the S gene. HBV DNA clones from five of
      these carriers had point mutations in the S gene, resulting in conversion from
      Ile-126 or Thr-126 of the wild-type virus to Ser-126 or Asn-126 in three carriers
      and conversion from Gly-145 to Arg-145 in three of them; clones with Asn-126 or
      Arg-145 were found in one carrier. All 12 clones from the other carrier had an
      insertion of 24 bp encoding an additional eight amino acids between Thr-123 and
      Cys-124. In addition, all or at least some of the HBV DNA clones from these
      carriers had in-phase deletions in the 5' terminus of the pre-S2 region. These
      results indicate that HBV escape mutants with mutations in the S gene affecting
      the expression of group-specific determinants would survive in some carriers
      after they seroconvert to antibody against surface antigen. Carriers with HBV
      escape mutants may transmit HBV either by donation of blood units without
      detectable surface antigen or through community-acquired infection, which would
      hardly be prevented by current hepatitis B immuneglobulin or vaccines.

PMID- 8139045
TI  - The human immunodeficiency virus type 1 Tat protein transactivates tumor necrosis
      factor beta gene expression through a TAR-like structure.
AB  - We have previously shown that the Tat protein of human immunodeficiency virus
      type 1 (HIV-1) transactivates tumor necrosis factor alpha and beta (TNF alpha and
      TNF beta) gene expression in HIV-1-infected and in tat-transfected T-lymphocytic
      and monocytic cell lines. The product encoded by the first exon of the tat gene
      (amino acids 1 to 72) is sufficient for this transactivation. Here we show that
      (i) the NF-kappa B and Sp1 binding sites of the TNF beta promoter are required
      for Tat-mediated transactivation and (ii) a predicted stem-loop structure in the
      TNF beta mRNA leader region, which resembles the Tat-responsive element of the
      HIV-1 long terminal repeat (TAR) and which is therefore termed TAR-like, is
      essential for TNF beta transactivation by Tat. These data suggest that similar
      promoter regulatory elements are necessary for Tat-mediated transactivation of
      both TNF beta and HIV-1 gene expression. This represents the first demonstration
      of a cellular gene with a regulatory element downstream of the transcriptional
      initiation site that, like TAR, may function as an RNA element.

PMID- 8139046
TI  - The Bel1 protein of human foamy virus contains one positive and two negative
      control regions which regulate a distinct activation domain of 30 amino acids.
AB  - The Bel1 transactivator is essential for the replication of human foamy virus
      (HFV). To define the functional domains of HFV Bel1, we generated random missense
      mutations throughout the entire coding sequence of Bel1. Functional analyses of
      24 missense mutations have revealed the presence of at least two functional
      domains in Bel1. One domain corresponds to a basic amino acid-rich motif which
      acts as a bipartite nuclear targeting sequence. A second, central domain
      corresponds to a presumed effector region which, when mutated, leads to dominant
      negative mutants and/or lacks transactivating ability. In addition, deletion
      analyses and domain-swapping experiments further showed that Bel1 protein
      contains a strong carboxy-terminal activation domain. The activating region is
      also capable of functioning as a transcription-activating domain in yeast cells,
      although it does not bear any significant sequence homology to the well
      characterized acidic activation domain which is known to function only in yeast
      and mammalian cells. We also demonstrated that the regions of Bel1 from residues
      1 to 76 and from residues 153 to 225 repressed transcriptional activation exerted
      by the Bel1 activation domain. In contrast, the region from residues 82 to 150
      appears to overcome an inhibitory effect. These results indicate that Bel1
      contains one positive and two negative regulatory domains that modulate a
      distinct activation domain of Bel1. These regulatory domains of Bel1 cannot
      affect the function of the VP16 activation domain, suggesting that these domains
      specifically regulate the activation domain of Bel1. Furthermore, in vivo
      competition experiments showed that the positive regulatory domain acts in trans.
      Thus, our results demonstrate that Bel1-mediated transactivation appears to
      undergo a complex regulatory pathway which provides a novel mode of regulation
      for a transcriptional activation domain.

PMID- 8139047
TI  - Role of alveolar type II cells and of surfactant-associated protein C mRNA levels
      in the pathogenesis of respiratory distress in mink kits infected with Aleutian
      mink disease parvovirus.
AB  - Neonatal mink kits infected with Aleutian mink disease parvovirus (ADV) develop
      an acute interstitial pneumonia with clinical symptoms and pathological lesions
      that resemble those seen in preterm human infants with respiratory distress
      syndrome and in human adults with adult respiratory distress syndrome. We have
      previously suggested that ADV replicates in the alveolar type II epithelial cells
      of the lung. By using double in situ hybridization, with the simultaneous use of
      a probe to detect ADV replication and a probe to demonstrate alveolar type II
      cells, we now confirm this hypothesis. Furthermore, Northern (RNA) blot
      hybridization showed that the infection caused a significant decrease of
      surfactant-associated protein C mRNA produced by the alveolar type II cells. We
      therefore suggest that the severe clinical symptoms and pathological changes
      characterized by hyaline membrane formation observed in ADV-infected mink kits
      are caused by a dysfunction of alveolar surfactant similar to that observed in
      respiratory distress syndrome in preterm infants. However, in the infected mink
      kits the dysfunction is due to the replication of ADV in the lungs, whereas the
      dysfunction of surfactant in preterm infants is due to lung immaturity.

PMID- 8139048
TI  - Analysis of N-terminal processing of hepatitis C virus nonstructural protein 2.
AB  - We determined the partial amino (N)-terminal amino acid sequence of hepatitis C
      virus p21 (nonstructural protein 2 [NS2]). Cleavage at the p21 (NS2) N terminus
      depended on the presence of microsomal membranes. The amino-terminal position of
      p21 (NS2) was assigned to amino acid 810 of the hepatitis C virus strain IIJ
      precursor polyprotein. Mutation of the alanine residue at position P1 of the
      putative cleavage site inhibited membrane-dependent processing. This alteration
      in processing together with the fact that hydrophobic amino acid residues are
      clustered upstream of the putative cleavage site suggested the involvement of a
      signal peptidase(s) in the cleavage. Furthermore, mutation analysis of this
      possible cleavage site revealed the presence of another microsome membrane
      dependent cleavage site upstream of the N terminus of p21 (NS2).

PMID- 8139049
TI  - Murine retrovirus-induced depletion of T cells is mediated through activation
      induced death by apoptosis.
AB  - ts1, a mutant of Moloney murine leukemia virus, causes neurologic disorders and
      acute immunodeficiency associated with the destruction of thymocytes and helper T
      cells. In this study, we examined whether apoptosis was involved in ts1-induced
      killings of T cells. Neonatal mice were inoculated with ts1, and 20 to 23 days
      postinoculation, when cytopathic effects on T cells normally appear, thymocytes
      and splenic lymphocytes were isolated and examined. Our results showed that
      several features of apoptosis were present in ts1-infected thymocytes and splenic
      lymphocytes. Apoptotic fragmented DNA, condensation of the chromatin, and
      enhanced cell death after stimulation with mitogens which was preventable with
      protein synthesis inhibitors, all of which are common features of apoptotic cell
      death, were observed in ts1-infected cells. Several other viruses, including
      human immunodeficiency virus, have been shown to cause apoptotic death of T
      cells. Here we show for the first time that a murine retrovirus which also
      induces immunodeficiency can cause apoptotic T-cell death. Future studies with
      this murine retrovirus may provide important results to help us better understand
      the mechanisms of retrovirus-induced apoptosis of T cells.

PMID- 8139050
TI  - Minute virus of mice infection modifies cellular transcription elongation.
AB  - Our previous observations indicated that upon infection with minute virus of mice
      (MVM), Ehrlich ascites cells lose a transcription elongation activity which is
      essential for the readthrough of the MVM attenuator. This was monitored by the
      ability of extracts from uninfected but not from infected cells to support
      readthrough of the P4 attenuator when added to partially purified transcription
      elongation complexes. We have investigated the nature of this change in
      transcription elongation following MVM infection. In this communication, we show
      that infection of Ehrlich ascites cells with MVM leads to a general shift in the
      length of nascent mRNA synthesized in isolated nuclei and separated by sucrose
      gradients. Furthermore, infection leads to attenuation of transcription of the
      cellular gene c-fos but not c-myc. We show biochemical evidence to support a
      model by which, following MVM infection, there is a functional reduction in the
      activity of a TFIIS-like general transcriptional elongation activity.

PMID- 8139051
TI  - Multigene families in African swine fever virus: family 505.
AB  - Sequencing of restriction fragment EcoRI A-SalI C of African swine fever virus
      has revealed the existence of a multigene family, designated family 505 because
      of the average number of amino acids in the proteins, composed of seven
      homologous and tandemly arranged genes. All the genes of family 505 are expressed
      during infection. Primer extension analysis showed that transcription is
      initiated a short distance (3 to 62 nucleotides) from the start codon of the
      corresponding open reading frame. The proteins of family 505 showed similarity to
      those of family 360 from African swine fever virus. In particular, a striking
      conservation of three regions at the amino terminus of the polypeptides was
      observed.

PMID- 8139052
TI  - Transformation of myelomonocytic cells by the avian myeloblastosis virus is
      determined by the v-myb oncogene, not by the unique long terminal repeats of the
      virus.
AB  - The avian myeloblastosis virus (AMV) induces acute monoblastic leukemia in
      chickens and transforms only myelomonocytic cells in vitro. The long terminal
      repeat (LTR) regulatory region of AMV is unique among the known classes of avian
      retrovirus LTRs. We demonstrate that the substitution of the AMV LTRs by Rous
      sarcoma virus LTRs did not alter the cell type specificity or the transforming
      ability of the virus.

PMID- 8139053
TI  - A soluble form of a receptor for subgroup A avian leukosis and sarcoma viruses
      (ALSV-A) blocks infection and binds directly to ALSV-A.
AB  - A receptor that confers susceptibility to infection by subgroup A avian leukosis
      and sarcoma viruses (ALSV-A) has been described (P. Bates, J. A. T. Young, and H.
      E. Varmus, Cell 74:1043-1051, 1993). A soluble form of the receptor was generated
      to determine whether this protein interacts directly with virus particles in the
      absence of other cell surface factors. The soluble protein comprised the
      extracellular region of the ALSV-A receptor fused to an antibody epitope tag and
      six histidine residues. Preincubating this protein with virus led to an efficient
      block to infection of avian cells by ALSV-A but had no effect on infection by
      ALSV-B, ALSV-C, or ALSV-D. Furthermore, an antibody directed against the
      introduced epitope tag immunoprecipitated ALSV-A particles bound to the soluble
      receptor. In contrast, other ALSV subgroups were not immunoprecipitated by this
      procedure. These data demonstrate that the cloned receptor interacts directly
      with ALSV-A and discriminates between different ALSV subgroups at the level of
      virus binding.

PMID- 8139054
TI  - Variability of the env gene in cynomolgus macaques persistently infected with
      human immunodeficiency virus type 2 strain ben.
AB  - The sequence variability of distinct regions of the proviral env gene of human
      immunodeficiency virus type 2 strain ben (HIV-2ben) isolated sequentially over 3
      to 4 years from six experimentally infected macaques was studied. The regions
      investigated were homologous to the V1, V2, V3, V4, V5, and V7 hypervariable
      regions identified in the env genes of HIV-1 and simian immunodeficiency virus
      SIVmac, respectively. In contrast to findings with HIV-1 and SIVmac, the V1- and
      V2-homologous regions were found to be highly conserved during the course of the
      HIV-2ben infection in macaques. The V3-homologous region showed a degree of
      variation comparable to that of HIV-1 but not of SIV. In the V4-, V5-, and V7
      homologous regions, mutation hot spots were detected in most reisolates of the
      infected monkeys. Most of these mutations occurred during the first 10 weeks
      after infection. After 50 weeks, new mutations were rarely detected. At most
      mutation sites, a dynamic equilibrium between the mutated viral isotype and the
      infecting predominant wild type was present. This equilibrium might prevent an
      accumulation of mutations in isolates later in the course of infection.

PMID- 8139055
TI  - Proteolytic cleavage of wild type and mutants of the F protein of human
      parainfluenza virus type 3 by two subtilisin-like endoproteases, furin and Kex2.
AB  - The fusion (F) protein of human parainfluenza virus type 3 contains the tribasic
      cleavage site R-T-K-R, which was altered by site-directed mutagenesis. Wild-type
      F protein and various mutants were expressed by recombinant vaccinia viruses. The
      endogenous endoprotease present in CV-1 cells cleaves F variants containing the
      furin recognition motif R-X-K/R-R but not variants containing the dibasic site K
      R or a single R at the cleavage site. A similar cleavage pattern was obtained
      when the subtilisin-like endoproteases Kex2 and furin were coexpressed with the
      wild type and mutants of the F protein. Peptidylchloromethylketone inhibitors
      mimicking basic cleavage sites prevent cleavage of the precursor Fo by the
      endogenous protease only when the furin-specific motif is present in the peptidyl
      portion. The data support the concept that furin is a cellular protease
      responsible for the activation of the F protein of human parainfluenza virus type
      3.

PMID- 8139056
TI  - In vivo replicative status and envelope heterogeneity of equine infectious anemia
      virus in an inapparent carrier.
AB  - The distribution and replicative status of equine infectious anemia virus (EIAV)
      DNA in the tissues of a well-characterized inapparent carrier horse were
      established by using the PCR technique. The EIAV pol region could be amplified in
      all of the tissues tested, including the cerebellum and periventricular tissue,
      at concentrations approximately 10(5)-fold less than in the same tissue from an
      acutely infected horse. Further analysis of the EIAV genome, with primer pairs
      diagnostic for sequential stages of reverse transcription, suggests that EIAV DNA
      in the brain, liver, and lymph nodes was incompletely synthesized. The products
      of reverse transcription were found to diminish progressively during first-strand
      synthesis, while products indicative of second-strand synthesis were observed
      only in kidney and spleen DNA samples. Sequences specific for different regions
      of the envelope could not be amplified from any of the tissues of the inapparent
      carrier, suggesting that the envelope is highly variable and may be subject to
      extensive drift. Together, the data suggest that low levels of EIAV replication
      persist without causing clinical disease in an inapparent carrier.

PMID- 8139057
TI  - Influence of education and occupation on the incidence of Alzheimer's disease.
AB  - OBJECTIVE: Several cross-sectional studies have found an association between
      Alzheimer's disease (AD) and limited educational experience. It has been
      difficult to establish whether educational experience is a risk factor for AD
      because educational attainment can influence performance on diagnostic tests.
      This study was designed to determine whether limited educational level and
      occupational attainment are risk factors for incident dementia. DESIGN: Cohort
      incidence study. SETTING: General community. PARTICIPANTS: A total of 593
      nondemented individuals aged 60 years or older who were listed in a registry of
      individuals at risk for dementia in North Manhattan, NY, were identified and
      followed up. INTERVENTIONS: We reexamined subjects 1 to 4 years later with the
      identical standardized neurological and neuropsychological measures. MAIN OUTCOME
      MEASURES: Incident dementia. RESULTS: We used Cox proportional hazards models,
      adjusting for age and gender, to estimate the relative risk (RR) of incident
      dementia associated with low educational and occupational attainment. Of the 593
      subjects, 106 became demented; all but five of these met research criteria for
      AD. The risk of dementia was increased in subjects with either low education (RR,
      2.02; 95% confidence interval [Cl], 1.33 to 3.06) or low lifetime occupational
      attainment (RR, 2.25; 95% Cl, 1.32 to 3.84). Risk was greatest for subjects with
      both low education and low life-time occupational attainment (RR, 2.87; 95% Cl,
      1.32 to 3.84). CONCLUSIONS: The data suggest that increased educational and
      occupational attainment may reduce the risk of incident AD, either by decreasing
      ease of clinical detection of AD or by imparting a reserve that delays the onset
      of clinical manifestations.

PMID- 8139058
TI  - Fecal occult blood screening for colorectal cancer. Is mortality reduced by
      chance selection for screening colonoscopy?
AB  - Annual fecal occult blood test (FOBT) screening using rehydrated Hemoccult slides
      has been reported in the Minnesota Colon Cancer Control Study to reduce
      colorectal cancer mortality by about 33%. However, some of the benefit of FOBT
      screening may come from "chance" selection of persons for colonoscopic
      examination because of the high positivity rate of FOBT (about 10%) that may
      occur for reasons other than a bleeding cancer or polyp. To determine how much
      this mechanism could account for the benefit of FOBT screening, we used a simple
      mathematical model to simulate the course of a cohort of screened persons,
      incorporating published data including those from the Minnesota study. The
      results suggest that one third to one half of the mortality reduction observed
      from FOBT screening in the Minnesota study may be attributable to chance
      selection for colonoscopy. We conclude that annual FOBT screening with
      rehydration is a haphazard method for selecting persons for colonoscopy.

PMID- 8139059
TI  - The relationship between the thrombotic and infectious complications of central
      venous catheters.
AB  - OBJECTIVES: To assess the frequency of thrombotic and infectious complications of
      long-term use of vascular catheters in cancer patients and to determine whether
      the two types of complication are related. DESIGN: Case series. SETTING: A 500
      bed tertiary cancer center. PATIENTS: Seventy-two cancer patients. INTERVENTIONS:
      During a 16-month period, postmortem examinations of catheterized veins and
      contralateral uncatheterized veins were done on all patients with indwelling
      central venous catheters who met study criteria. MAIN OUTCOME MEASURES: Catheter
      related septicemia determined by clinical and microbiological data as well as
      postmortem pathology; venous pathological changes such as mural hemorrhage,
      thrombosis, calcification, ulceration, and inflammation. RESULTS: Premortem
      clinical and microbiological data were obtained retrospectively on all patients.
      Pathological changes were noted in 35 catheterized veins (49%) compared with five
      contralateral control veins (9.2%) (P < .001). Mural thrombi were noted in 27
      catheterized veins (38%) compared with only one contralateral control vein (1.4%)
      (P < .001). Other pathological changes consisted of four central venous catheter
      related mural thrombi (5.6%) in the right atrium and four instances (5.6%) of
      nonbacterial thrombotic endocarditis, three involving the tricuspid and one the
      mitral valves. Seven patients had catheter-related septicemia. Of the 31 patients
      with mural thrombosis of the catheterized vein or right atrium, seven developed
      catheter-related septicemia, whereas none of the 41 patients with normal
      catheterized veins and atria developed catheter-related septicemia (P < .01).
      CONCLUSIONS: Thrombotic complications are common in catheterized veins and are
      often associated with catheter sepsis.

PMID- 8139060
TI  - Health care decision making for persons with disabilities. An alternative to
      guardianship.

PMID- 8139061
TI  - Tacrine for Alzheimer's disease. Which patient, what dose?

PMID- 8139062
TI  - Lipoprotein(a) in coronary heart disease. Is it a risk factor after all?

PMID- 8139063
TI  - Membership has its costs.

PMID- 8139064
TI  - Medical student abuse: an international phenomenon.
AB  - OBJECTIVE: To evaluate the prevalence of physical and psychological mistreatment
      of medical students at two medical schools in Finland. STUDY DESIGN AND SETTING:
      To enable comparison between Finnish and American students, we used the American
      Medical Association's Office of Education Research questionnaire. RESULTS: Three
      of every four students surveyed reported experiencing some kind of mistreatment
      during their medical education. Students most commonly reported sexual
      mistreatment, usually as slurs and sexual discrimination, from classmates,
      preclinical teachers, clinical teachers, clinicians, nurses, and patients. Other
      forms of verbal abuse, psychological mistreatment, and physical threats were also
      reported. CONCLUSIONS: All forms of mistreatment were reported occurring less
      frequently than in the United States; still, the level of such behavior was high.
      The results suggest the need for more international awareness and debate
      regarding the habits and behavior of teaching staff in medical schools.

PMID- 8139065
TI  - Breaking bad news to patients.

PMID- 8139066
TI  - A piece of my mind. Frozen in time.

PMID- 8139067
TI  - Pollution and poverty overlap becomes issue, administration promises action.

PMID- 8139068
TI  - For biomedical research, is reassurance enough?

PMID- 8139069
TI  - Military becomes smoke-free work site this week.

PMID- 8139070
TI  - AMA 'reform event' reflects physicians' new role.

PMID- 8139071
TI  - From the Health Care Financing Administration.

PMID- 8139072
TI  - From the Centers for Disease Control and Prevention. Heterosexually acquired AIDS
      -United States, 1993.

PMID- 8139073
TI  - From the Centers for Disease Control and Prevention. Update: impact of the
      expanded AIDS surveillance case definition for adolescents and adults on case
      reporting--United States, 1993.

PMID- 8139074
TI  - Is there tension in hypertension?

PMID- 8139075
TI  - Treatment of status epilepticus.

PMID- 8139076
TI  - Treatment of status epilepticus.

PMID- 8139077
TI  - Anxiety during MRI.

PMID- 8139078
TI  - The use of mammography for screening.

PMID- 8139079
TI  - The dental AIDS cases--murder or an unsolvable mystery?

PMID- 8139080
TI  - Measuring splanchnic oxygenation by gastric tonometry.

PMID- 8139081
TI  - Errors in drug dosages. Correction.

PMID- 8139082
TI  - Situs inversus due to Canadian medical system? No: bashful author covered belly
      button.

PMID- 8139083
TI  - A 30-week randomized controlled trial of high-dose tacrine in patients with
      Alzheimer's disease. The Tacrine Study Group.
AB  - OBJECTIVE: To evaluate the efficacy and safety of high-dose tacrine hydrochloride
      over 30 weeks in patients with probable Alzheimer's disease. DESIGN: A 30-week
      randomized, double-blind, placebo-controlled, parallel-group trial. SETTING:
      Outpatients at 33 US centers. PATIENTS: Men and women at least 50 years of age
      with mild to moderate Alzheimer's disease and otherwise in good health.
      INTERVENTIONS: Group 1 received placebo; group 2 received 40 mg/d of tacrine for
      6 weeks, then 80 mg/d for 24 weeks; groups 3 and 4 received 40 mg/d of tacrine
      for 6 weeks, 80 mg/d for 6 weeks, and 120 mg/d for 6 weeks. Group 3 remained on a
      dosage of 120 mg/d for a total of 18 weeks; after 6 weeks at 120 mg/d, group 4
      titrated to 160 mg/d for the last 12 weeks. PRIMARY OUTCOME MEASURES: Clinician
      Interview-Based Impression (CIBI), Alzheimer's Disease Assessment Scale-
      Cognitive subscale (ADAS-Cog), and Final Comprehensive Consensus Assessment
      (FCCA). RESULTS: A total of 663 patients entered the study; 653 patients were
      included in an intent-to-treat (ITT) analysis; 263 had evaluable data at 30
      weeks. The results of the ITT analysis revealed significant (P < or = .05) dose
      response trends and between-group comparisons on CIBI and ADAS-Cog. In evaluable
      patients, significant dose-response trends were observed for all three primary
      measures (P < or = .001). Significant differences in favor of 160 mg/d of tacrine
      vs placebo were observed on the CIBI (P < or = .002) and ADAS-Cog and FCCA (P <
      or = .001), as well as caregiver-global and quality-of-life assessments (P < or =
      .05). On the CIBI, 23% and 42% of tacrine-treated patients in the ITT and
      evaluable-patient populations, respectively, were rated improved compared with
      17% and 18% of placebo patients, respectively. The primary reasons for withdrawal
      of tacrine-treated patients were asymptomatic liver transaminase elevations (28%)
      and gastrointestinal complaints (16%). These adverse events were reversible on
      discontinuation of treatment, and many patients were able to restart tacrine.
      CONCLUSIONS: Tacrine produced statistically significant, dose-related
      improvements on objective performance-based tests, clinician- and caregiver-rated
      global evaluations, and measures of quality of life. There was no evidence that
      the large number of patient withdrawals biased the overall conclusions of the
      study.

PMID- 8139084
TI  - Hepatotoxic effects of tacrine administration in patients with Alzheimer's
      disease.
AB  - OBJECTIVE: To characterize the hepatic effects of tacrine treatment in patients
      with Alzheimer's disease. DESIGN: Controlled trials of tacrine therapy consisting
      of two blinded, parallel-group trials; three blinded, enrichment-design trials;
      and their respective open-label extensions. SETTING: Multicenter clinical trials
      in the United States, France, and Canada. PATIENTS: A total of 2446 men and women
      at least 50 years of age with a diagnosis of probable Alzheimer's disease of mild
      to moderate severity and in good health without significant hepatic,
      cardiovascular, or renal disease. INTERVENTION: Administration of tacrine vs
      placebo, with weekly measurement of serum hepatic enzymes. MAIN OUTCOME MEASURES:
      Incidence, maximum severity, and timing of event for serum alanine
      aminotransferase (ALT) elevation. RESULTS: Among the 2446 patients who received
      tacrine in clinical trials, ALT levels greater than the upper limit of normal
      (ULN) occurred on at least one occasion in 1203 patients (49%), ALT levels
      greater than three times the ULN occurred in 621 patients (25%), and ALT levels
      greater than 20 times the ULN occurred in 40 patients (2%). The elevated ALT
      levels were generally asymptomatic and occurred more frequently in women than
      men. The mean time from initiation of tacrine treatment to first ALT level
      greater than three times the ULN was 50 days, and 90% of all initial ALT levels
      greater than three times the ULN occurred during the first 12 weeks of treatment.
      Of 145 patients who discontinued tacrine treatment because of an ALT level
      greater than three times the ULN and were rechallenged, 127 (88%) were able to
      resume long-term therapy with the drug. In all instances, discontinuing tacrine
      completely reversed elevations in ALT levels, and no deaths related to
      hepatotoxicity occurred. CONCLUSIONS: These data suggest that the potential for
      serious hepatic toxicity can be reduced through careful monitoring of ALT levels
      in patients who may benefit from tacrine therapy.

PMID- 8139085
TI  - Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid
      Research Clinics Coronary Primary Prevention Trial.
AB  - OBJECTIVE: To examine the relationship between elevated levels of lipoprotein(a)
      [Lp(a)] and coronary heart disease (CHD) risk in a prospective study. DESIGN:
      Nested case-control study. The cohort consisted of participants in the Lipid
      Research Clinics Coronary Primary Prevention Trial. SETTING: Lipid research
      clinics. PARTICIPANTS: The Lipid Research Clinics Coronary Primary Prevention
      Trial participants (n = 3806) were men, aged 35 to 59 years, with plasma
      cholesterol levels of 6.85 mmol/L (265 mg/dL) or greater, low-density lipoprotein
      cholesterol levels of 4.91 mmol/L (190 mg/dL) or greater, and triglyceride levels
      less than 3.39 mmol/L. Subjects were randomly assigned to either cholestyramine
      or placebo treatment. The Lp(a) levels were measured in plasma samples obtained
      prior to randomization in 233 cases (participants who developed CHD in the course
      of the study) and 390 matched CHD-free controls. A total of 96.95% of the
      subjects were white, 2.25% were black, and 0.80% were of other race. MAIN OUTCOME
      MEASURE: Coronary heart disease (either fatal or nonfatal) events during a follow
      up of 7 to 10 years. RESULTS: The Lp(a) levels were significantly higher (21%) in
      cases than in controls (23.7 mg/dL [0.59 mmol/L] and 19.5 mg/dL [0.49 mmol/L],
      respectively; P < .02). This difference was still statistically significant (P <
      .01) after controlling for age, body mass index, cigarette smoking, blood
      pressure, low-density lipoprotein cholesterol level, and high-density lipoprotein
      cholesterol level. When subjects were divided by treatment, both cholestyramine
      treated and placebo-treated CHD subjects had Lp(a) levels 20% to 22% greater than
      their matched controls. However, possibly because of smaller sample sizes, these
      differences were no longer statistically significant. CONCLUSIONS: Our data are
      consistent with the concept that an elevated Lp(a) level is an independent risk
      factor for CHD in hypercholesterolemic white men.

PMID- 8139086
TI  - Effects of intravenous verapamil on atrial vulnerability.
AB  - To investigate the effects of verapamil on indicators of atrial vulnerability, we
      examined 30 patients with paroxysmal supraventricular tachycardia who received
      intravenous verapamil during an electrophysiologic study. Single atrial
      extrastimuli were given before and after intravenous administration of verapamil
      to induce repetitive atrial firing (RAF) or atrial fibrillation, and to examine
      the maximum A2/A1, which was defined as the maximum ratio of the duration of the
      atrial electrogram resulting from premature stimulation (A2) to that resulting
      from the basic drive beat (A1). The maximum A2/A1 increased from 145 +/- 20% to
      154 +/- 25% (p < 0.02) after verapamil administration. The maximum A2/A1 in
      patients in whom neither RAF nor atrial fibrillation were induced both before and
      after verapamil were smaller than those in patients in whom RAF was induced only
      after verapamil (before; 138 +/- 20% vs 165 +/- 15%, p < 0.02. after; 144 +/- 22%
      vs 172 +/- 17%, p < 0.05). RAF or atrial fibrillation was induced only after
      verapamil in 6 patients, who showed a maximum A2/A1 before verapamil of 150% or
      more. These data suggest that verapamil may induce repetitive atrial firing and
      possibly atrial fibrillation in some predisposed patients, especially in those
      that have a greater maximum A2/A1, which may be an indicator of local intraatrial
      conduction delay before drug infusion.

PMID- 8139087
TI  - Perfusion reserve of coronary collateral circulation and its significance in the
      development of exercise-induced ischemia in patients with multivessel disease.
AB  - To assess the perfusion reserve of coronary collateral circulation, we analyzed
      exercise-stress tomographic thallium-201 myocardial images in 12 patients who had
      total occlusion in the right coronary artery (RCA) or left circumflex coronary
      artery (LCX) with well-developed collateral circulation and 90% stenosis in the
      left anterior descending coronary artery (LAD). In 6 of the 12 patients, the
      collateral circulation was non-jeopardized (group A). In the remaining 6
      patients, the collateral circulation was jeopardized (group B). All 6 of the
      patients in group A had an exercise-induced decrease in thallium uptake in the
      segments supplied by the occluded RCA or LCX with collateral circulation, and 3
      (50%) of these 6 also showed a decrease in thallium uptake in the segments
      supplied by the LAD. All 6 of the patients in group B also had an exercise
      induced decrease in thallium uptake in the segments supplied by the occluded RCA
      or LCX with collateral circulation, but none showed a decrease in thallium uptake
      in the segments supplied by the LAD. In conclusion, the perfusion reserve of
      collateral circulation is equal to or less than 90% stenosis and myocardial
      ischemia occurs first in the collateralized segments during exercise in patients
      with jeopardized collateral circulation.

PMID- 8139088
TI  - Comparison of the effects of exercise and isoproterenol on the antegrade
      refractory period of the accessory pathway in patients with Wolff-Parkinson-White
      syndrome.
AB  - The effects of exercise and isoproterenol infusion on the antegrade effective
      refractory period of the accessory pathway (ERP-AP) were compared in 10 patients
      with Wolff-Parkinson-White (WPW) syndrome. During an electrophysiologic study,
      the ERP-AP (paced cycle length: 400 msec) was measured before and during
      isoproterenol infusion at a rate of 1 microgram/min. On the next day, a symptom
      limited ergometer exercise test was performed and the ERP-AP (paced cycle length:
      400 msec) was measured before and during the test using an indwelling atrial
      electrode catheter. Isoproterenol infusion and the exercise test increased the
      heart rate from 84 +/- 24 to 122 +/- 17 beats/min and from 85 +/- 25 to 128 +/-
      25 beats/min, respectively (p = NS isoproterenol versus exercise). The ERP-AP was
      shortened from 268 +/- 34 to 230 +/- 19 msec with isoproterenol infusion (p <
      0.001) and from 273 +/- 42 to 237 +/- 31 msec with the exercise test (p < 0.001).
      There was no significant difference between the effects of isoproterenol and
      exercise. The percent change in the ERP-AP with exercise (Y) was significantly
      correlated to that with isoproterenol infusion (X) (Y = -3.04 + 0.70X, r = 0.92,
      p < 0.001). In conclusion, isoproterenol infusion at the present dose shortens
      the ERP-AP to the same degree as exercise, and thus is useful for predicting the
      exercise-induced shortening of the ERP of the accessory pathway in patients with
      WPW syndrome.

PMID- 8139089
TI  - Impaired microvascular vasodilator reserve in chronic cigarette smokers--a study
      of post-occlusive reactive hyperemia in the human finger.
AB  - To assess the vasodilator reserve in microcirculation, post-occlusive reactive
      hyperemia was examined in 21 chronic cigarette smokers (mean age; 50 +/- 7 years)
      and 21 non-smokers (mean age; 51 +/- 6 years), who were all healthy males.
      Reactive hyperemia was induced by occluding the digital artery at the base of the
      middle finger, and the increase in skin blood flow (delta flow) was analyzed with
      a laser Doppler flowmeter. Occlusion time was increased in a step-wise manner
      from 30 sec up to 300 sec. Baseline skin blood flow was similar in both groups
      (smoker, 27 +/- 9 ml/min/100 g; non-smoker, 25 +/- 10 ml/min/100 g, NS). The
      delta flow in smokers was significantly less (23%-59%) than that in non-smokers.
      Furthermore, the reduced delta flow in smokers was inversely correlated with
      Brinkmann's smoking index (r = 0.567, p < 0.01). These results indicate that
      chronic cigarette smoking impairs the microvascular response to transient
      ischemia, and that this impairment correlates with the intensity of the smoking
      habit.

PMID- 8139090
TI  - Ventricular unloading and improvement in left ventricular function after
      angiotensin converting enzyme inhibition with enalapril in patients with chronic
      congestive heart failure.
AB  - To clarify how angiotensin converting enzyme inhibition affects left ventricular
      function through ventricular unloading, ventricular wall stress, ventricular
      volumes, and other cardiac indices and exercise tolerance were evaluated in 17
      patients with mild to moderate chronic congestive heart failure before and after
      3 months of treatment with enalapril. Echocardiographic examination revealed that
      treatment with this angiotensin converting enzyme inhibitor resulted in
      significant reductions in end-systolic wall stress (117 +/- 25 to 89 +/- 28
      g/cm2, p < 0.01) and left ventricular volume indices (end-diastolic: 163 +/- 56
      to 143 +/- 60; end-systolic 99 +/- 51 to 77 +/- 57 ml/m2 p < 0.01). Ejection
      fraction (42 +/- 11 to 48 +/- 13%, p < 0.01) and systolic blood pressure/end
      systolic volume (SBP/ESV; 1.06 +/- 0.30 to 1.33 +/- 0.48 mmHg/ml, p < 0.01) were
      both increased. By radionuclide ventriculography, ejection fraction and peak
      ejection rate (2.30 +/- 0.74 to 2.80 +/- 0.76 EDV/sec, p < 0.01) were increased,
      while time to peak ejection, time to peak filling, and peak filling rate were
      unchanged. Heart rate and double product at exercise were decreased and delta EF
      was significantly increased (-1.4 +/- 4.1 to 1.6 +/- 4.4%, p < 0.02). The
      decrease in end-systolic wall stress was consistently related to both the
      increase in ejection fraction and SBP/ESV, while the decrease in end-diastolic
      volume was related only to SBP/ESV and not to ejection fraction. Furthermore,
      there was a direct relationship between the decrease in systolic wall stress and
      the decrease in end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139091
TI  - Excellent prognosis of Japanese patients with chest pain and normal or nearly
      normal coronary arteries--2- to 13-year follow-up of 274 patients after coronary
      cineangiography.
AB  - Although the prognosis of patients with chest pain and normal coronary arteries
      is reportedly good in the Western literature, it is unclear in Japan. The purpose
      of this study was to examine the natural history of 274 consecutive patients with
      chest pain and normal or nearly normal coronary arteries, and to determine
      whether the possibility of minor coronary artery disease has clinical
      implications as a prodromal factor of other heart diseases. Six of the patients
      died during the mean observation period of 6 years (74.5 +/- 35.4 months): 2
      cancer, 3 cerebro-vascular accident, and 1 renal failure death. Three additional
      patients suffered from nonfatal cerebro-vascular accidents. Eleven patients were
      readmitted for evaluation of chest pain, and 4 of these were diagnosed as having
      vasospastic angina. Progression of significant coronary artery disease was not
      detected in these 11 patients with repeated coronary angiography. None of the
      patients in this study developed fatal or nonfatal myocardial infarction. A small
      number of patients (36/240, 15.0%) continued to suffer from chest pain. None of
      the patients developed cardiomyopathies or valvular heart diseases. Our
      observations indicate that the prognosis of chest pain with normal or nearly
      normal coronary arteries is better than that presented in the Western reports.

PMID- 8139092
TI  - Comparison of manual and computer-assisted automatic measurements of wall
      thickness of the left ventricle in two-dimensional echocardiography.
AB  - To investigate the clinical applicability of automatic analysis of wall thickness
      in two-dimensional echocardiography, computer-assisted and conventional manual
      methods were compared in 26 cases. An echo threshold was automatically set in
      short-axis echo images through a discriminatory variance analysis of the signal
      to-noise ratio. A fixed standard was determined inside the left ventricle using
      the circle window method, which we developed previously. Two abrupt echo
      reflections were selected as candidate points for the borders, and an outward
      search was conducted in all directions from a fixed standard to separately
      delineate the endocardial and epicardial interfaces. Interpolation using a spline
      function was applied to these points to complete the border lines.
      Differentiation was also used to eliminate the anterior and posterior papillary
      muscles. Significant correlations of r = 0.98 were found between the computer and
      manual assessments of the epicardial and endocardial intraluminal ventricular
      areas (p < 0.01). A correlation of r = 0.87 was also obtained for myocardial wall
      thickness as determined by the 2 methods (p < 0.01). Variability of the
      reproducibility using the computer method was 0.22% for the epicardial area and
      0.64% for the endocardial area. These results confirm that computer-aided
      automatic measurement of wall thickness is clinically applicable to two
      dimensional echocardiography.

PMID- 8139093
TI  - Contribution of chamber compliance and left ventricular minimum pressure to
      abnormal left ventricular filling dynamics.
AB  - This study was designed to clarify whether changes in transmitral flow velocity
      patterns in left ventricular (LV) dysfunction are determined primarily by changes
      in left atrial (LA) pressure and LV relaxation, and, if not, to determine the
      contribution of changes in other parameters. Two levels of acute LV dysfunction
      were produced in 11 dogs by coronary microembolization, and pulsed Doppler
      transmitral flow velocity patterns and hemodynamic parameters were recorded. The
      mean ratio of peak early diastolic filling velocity (E) to peak late diastolic
      filling velocity decreased with mild LV dysfunction (LV end-diastolic pressure of
      between 12 and 17 mmHg), and redistribution of diastolic filling to early
      diastole was observed with severe LV dysfunction (LV end-diastolic pressure of >
      or = 18 mmHg). Changes in E correlated best with those in the LA-LV pressure
      gradient integral. Multiple linear regression analysis of the changes in possible
      determinants of the pressure gradient integral, i.e., LA to LV crossover
      pressure, LV time constant, LV minimum pressure, and LA and LV chamber
      compliance, yielded a highly significant correlation with the changes in E.
      However, analysis of only the changes in the crossover pressure and the time
      constant showed a very poor correlation. Thus, changes in chamber compliance and
      LV minimum pressure, in addition to the changes in LA pressure and LV relaxation,
      may significantly affect the changes in E that are associated with LV
      dysfunction.

PMID- 8139094
TI  - Effects of NG-monomethyl-L-arginine, indomethacin, and aspirin on the
      vasodepressor response to low doses of endothelin-1 and endothelin-3 in rats.
AB  - Low doses (< or = 100 pmol/kg) of endothelin-1 (ET-1) and endothelin-3 (ET-3)
      elicited a fall in mean arterial pressure (MAP) and a dose-related reduction in
      hindquarter vascular resistance in anesthetized rats. The depressor response to
      low doses of ET-1 or ET-3 was short-lived (about 10 sec) and reversible. High
      doses (> or = 200 pmol/kg) of ET-1 and ET-3 elicited a biphasic response; an
      initial fall in MAP followed by a gradual increase in MAP. The pressor response
      to large doses of ET-3 was less than that to large doses of ET-1. On the other
      hand, the depressor response to low doses of ET-3 was similar to that to low
      doses of ET-1. Both ET-1 and ET-3 at low doses exhibited primarily a vasodilatory
      activity. Pretreatment with NG-monomethyl-L-arginine (L-NMMA), a compound that
      inhibits nitric oxide (NO) production by endothelial cells, attenuated the
      hypotensive and hindquarter vasodilating effects of low doses of these
      isopeptides, indicating that the hindquarter vasodilating responses to these
      peptides depend upon the release of NO from endothelial cells. On the other hand,
      pretreatment with either aspirin or indomethacin did not alter the hypotensive or
      the hindquarter vasodilating effects of either ET-1 or ET-3, indicating that
      cyclooxygenase products may not be involved in the vasodepressive mechanisms of
      these peptides. L-NMMA attenuated the vasodilating effects of these peptides, but
      did not completely inhibit the response, suggesting that NO production by
      endothelial cells plays only a partial role in the vasodilation of ET in
      vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139095
TI  - Right atrial myxoma with right to left shunt and coronary artery disease.
AB  - Surgical treatment of a right atrial myxoma with a right-to-left shunt and
      coronary artery disease was successfully performed in a 61-year-old man. The
      interatrial shunt occurred through a patent foramen ovale and was the result of a
      high central venous pressure due to tricuspid stenosis and regurgitation. Instead
      of right heart catheterization and cardioangiography, we chose an intraoperative
      blood-gas study to diagnose the intracardiac shunt. Preoperative polycythemia and
      hypoxemia were improved after removal of the tumor and closure of the patent
      foramen ovale.

PMID- 8139096
TI  - [Blast self-renewal capacity as a target of the treatment in acute myelocytic
      leukemia].

PMID- 8139097
TI  - [Treatment of acute lymphoblastic leukemia in adults by the modified protocol of
      L-10M (Sloan-Kettering): long-term outcome].
AB  - From January 1984 to April 1988, we treated 20 patients with adult lymphoblastic
      leukemia (ALL) and 2 patients with lymphoblastic lymphoma with a protocol which
      we modified L-10M of Sloan-Kettering Cancer Center. Since the median follow up
      time is now over 5 years, we report the most recent outcome. Thirteen patients
      were male and 9 were female. The median age was 31, ranging from 15 to 71 years
      of age, and there were no Ph1 positive patients. The complete remission (CR) rate
      was 81.8%. Median CR duration was 32 months and the 5-year continuous CR rate was
      33.3%. No significant prognostic factor for CR rate was found. Age at achievement
      CR and duration were significant prognostic factors. The 5-year continuous CR
      rate of patients below 35 years old was 54.5%. In this group the leukocyte count
      was a significant prognostic factor. All patients with a leukocyte count above 1
      x 10(4)/microliters relapsed. However, in patients with a WBC below 1 x
      10(4)/microliters, the 5-year continuous CR rate was 75%. Based on these results,
      it seems reasonable to treat patients with ALL by different therapeutic
      strategies according to the risk factors.

PMID- 8139098
TI  - [Bronchopulmonary lesions in cases of chronic graft-versus-host disease (cGVHD)].
AB  - We have studied bronchopulmonary lesions that developed in 3 allogeneic bone
      marrow recipients between days 120 and 250 post-transplant. Two cases had
      extensive chronic GVHD at the time of onset. All patients complained of low-grade
      fever, dry cough, and shortness of breath. The bronchopulmonary lesions were
      characterized by hypoxemia with increased AaDO2 and bilateral multiple
      noncircumscribed interstitial shadows on chest CT scan. Broncho-alveolar lavage
      (BAL) showed elevated numbers of lymphocytes in BAL fluid in all cases. BAL fluid
      was negative for CMV, pneumocystis carinii cysts, bacteria and fungi in all
      cases. The results of transbronchial lung biopsy (TBLB) showed interstitial
      infiltration of lymphocytes in all 3 cases. The bronchopulmonary lesions were
      improved by either starting or increasing the dose of immunosuppressants. These
      findings and clinical courses suggest that the bronchopulmonary lesions in these
      patients were related to chronic GVHD.

PMID- 8139099
TI  - [Complications of marrow harvesting for transplantation].
AB  - Seventy-four responses were received from a questionnaire which had been mailed
      to 91 bone marrow transplantation institutes throughout Japan to assess the
      activity of bone marrow transplantation and complications in bone marrow donors.
      A total of 2329 bone marrow harvests, performed from 1688 adult donors and 641
      child donors for allogeneic or syngeneic transplantation up to August 1992, were
      available for study. Analyses of the responses showed slight diversity regarding
      the marrow harvesting preparation and methods of the different bone marrow
      programs. The resulting perioperative complications were principally caused by
      anesthesia: 73 episodes of hypotension including one death 18 months later, seven
      of arrhythmia, one of respiratory arrest, three of mental confusion, one of
      asthma, one of malignant hyperthermia, one tooth injury and one broken aspiration
      needle. The postoperative complications were chiefly caused by marrow aspiration
      per se: 731 episodes of transient fever, 26 of long-lasting pain or discomfort,
      10 episodes of liver dysfunction including two cases of non-A, non-B hepatitis,
      four cases of infection, one episode of hypotension, one of dysuria and one case
      of keloid formation. The study further revealed that the frequency of
      complications was lower in child donors than in adult donors.

PMID- 8139100
TI  - [Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all
      trans-retinoic acid].
AB  - This paper describes the treatment of promyelocytic blast crisis of chronic
      myelogenous leukemia with all-trans-retinoic acid (ATRA). The patient, a 22-year
      old male, was diagnosed to have APL and had been treated with busulfan and then
      with three and half years interferon (IFN) alpha in the chronic phase. A
      cytogenetic study of blast cells showed the t(1;17) (p11;q11) translocation as
      the second chromosomal abnormality without morphological abnormality of
      chromosome 15. Molecular analysis showed cells to have a chimera gene consisted
      of PML and retinoic acid receptor alpha genes. Though maturation and
      differentiation of leukemic cells were seen after ATRA therapy, hematological
      complete remission did not occur. The ineffectiveness of ATRA may be dut to
      different pathological conditions from de novo APL, or progressive reduction in
      plasma ATRA concentration as reported by Muindi et al. When our case was compared
      with a similar case reported by Wiernick et al., both cases were treated with IFN
      alpha in the chronic phases, had no t(15;17) translocation involving No.1
      chromosome abnormality and did not develop complete remission after ATRA therapy.

PMID- 8139101
TI  - [Successful treatment of chemotherapy-resistant adult T cell leukemia/lymphoma by
      irinotecan hydrochloride (CPT-11)].
AB  - A 62-year-old man was hospitalized in March 1990 due to upper abdominal
      discomfort and anorexia. The chest X-ray revealed an upper anterior mediastinal
      tumor, and abdominal ultrasound showed lymphadenopathy. Endoscopic examination of
      the stomach revealed a large, irregular ulcer, which was histologically confirmed
      to be malignant lymphoma by biopsy. Serum anti-HTLV-1 antibody was positive. A
      diagnosis of ATLL (lymphoma type) was made. The usual therapy for this disease,
      including the LSG4 and RCM protocols, was only transiently effective. Therefore,
      the patient was treated with CPT-11 (40 mg/m2) by intravenous infusion on 3
      consecutive days with weekly repetition in November 1990. Complete remission was
      obtained after 2 weeks of treatment, and was maintained for 5 months. This case
      suggests that CPT-11 may be effective for the treatment of ATL.

PMID- 8139102
TI  - [Drug-resistant multiple myeloma with high serum levels of lactate dehydrogenase
      and neutrophil infiltration in pleural effusion].
AB  - A 57-year-old male patient with multiple myeloma showed an aggressive course with
      characteristic clinical features: rapid progression of plasmacytoma in the
      thoratic cavity, high serum levels of lactate dehydrogenase (LDH), which is
      usually not elevated in myeloma patients, and neutrophil infiltration in pleural
      effusion. Despite treatment with vincristine, doxorubicin and dexamethasone, the
      tumor mass had become non-responsive to chemotherapy and been increasing in size
      in correlating with the increase of serum levels of LDH. The patient died of
      respiratory failure 4 months after treatment. Thus the serum level of LDH is
      thought to be a useful clinical marker to monitor disease activity as well as
      other markers such as monoclonal immunoglobulin and beta 2-microglobulin. To
      investigate the cause of neutrophil infiltration into pleural effusion, we
      cultured plasma cells obtained from the effusion for 3 days in serum-free medium
      and examined the activity of neutrophil chemotaxis in the culture supernatant.
      The results showed chemotactic activity in the supernatant as high as in positive
      controls stimulated with a chemotactic factor, formyl-methionyl leucyl phenyl
      alanine, suggesting that tumor cells produced neutrophil chemotactic factor(s).

PMID- 8139103
TI  - [Malignant lymphoma with various neuropsychological symptoms].
AB  - A case of malignant lymphoma presented with various neuropsychological symptoms
      which made it difficult to achieve the diagnosis and therapy. A 9-year-old boy
      was referred to our hospital with complaints of psychological symptoms,
      impairment of consciousness and generalized convulsive seizures. A lumbar
      puncture revealed infiltration of numerous blasts which were positive for
      immature B cell markers. CT scan showed a mass in the right ethmoidal sinus, but
      no space occupying lesion in the brain. The tumor cells in the right ethmoidal
      sinus had the same phenotypes as those in the CSF. Thus a diagnosis of non
      Hodgkin's lymphoma, developing in the right ethmoidal sinus and infiltrating into
      the central nervous system, was established. The blast cells in the liquor and
      the tumor of the right ethmoidal sinus disappeared after induction of systemic
      chemotherapy, irradiation and intrathecal chemotherapy. However, intracranial
      bleeding occurred during the chemotherapy. He died of respiratory failure 10
      months after the start of treatment.

PMID- 8139104
TI  - [AML1 gene rearrangements, but no 8;21 translocation in a child with acute
      myeloblastic leukemia (M2)].
AB  - A 3-year-old girl developed fever and bilateral exophthalmos. Her initial
      peripheral blood counts on admission were; Hb8.7 g/dl, Plt. 10.6 x
      10(4)/microliters, and WBC 30,890/microliters with 31% peroxidase-positive
      blasts, some of which contained Auer rods. The bone marrow smears showed 22%
      blasts with a certain degree of maturation. She was diagnosed as having M2 type
      AML. Computed tomography revealed bilateral retoro-orbital tumor. The bone marrow
      karyotype showed no 8;21 translocation but a loss of one sex chromosome.
      Molecular analysis of the bone marrow cells disclosed rearrangements of the AML1
      gene. Chimeric mRNA coded by the AML1-MTG8 gene was also detected by the RT-PCR
      method. We concluded that this patient had a masked 8;21 translocation in her
      leukemic cells.

PMID- 8139105
TI  - [Hemophagocytic syndrome in a patient with immunoblastic lymphadenopathy-like T
      cell lymphoma].
AB  - We report a 70-year-old male case of immunoblastic lymphadenopathy-like T-cell
      lymphoma (IBL-T) complicated by hemophagocytic syndrome (HPS) as a terminal
      event. The patient experienced fever and systemic lymphadenopathy after 22
      months' remission of IBL-T. He developed acute hepatic failure and consumption
      coagulopathy rapidly, and died on the 7th hospital day. Serum levels of
      cytokines, including interferon-gamma and tumor necrosis factor-alpha, were
      elevated. Postmortem bone marrow aspirate showed a marked proliferation of benign
      looking macrophages, some of which phagocytized erythrocytes and platelets.
      Because there were no preceding viral or bacterial infections, the HPS of this
      case was assumed to be associated with IBL-T at relapse.

PMID- 8139106
TI  - [Lennert's lymphoma associated with the syndrome of inappropriate secretion of
      antidiuretic hormone and autoimmune hemolytic anemia].
AB  - We report a case of Lennert's lymphoma complicated by the syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH) and autoimmune hemolytic
      anemia (AIHA). A 76-year-old female patient was admitted to our hospital because
      of cervical lymph node swelling. A diagnosis of Lennert's lymphoma was made by
      histological examination of the biopsied lymph node. She was also diagnosed as
      SIADH and AIHA. After the patient was treated with COP-BLAM therapy, lymph
      adenopathy, SIADH and AIHA improved. However, lymph node swelling and
      hyponatremia became exacerbated again after the third course of COP-BLAM therapy.
      Then she was treated with IMV-triple P therapy. Eventually, she died of
      aspergillus pneumonia. The etiology of her SIADH was suggested to be an abnormal
      feedback mechanism of ADH secretion due to the infiltration of lymphoma cells
      into the diencephalic-hypophysial system.

PMID- 8139107
TI  - [A study of E2A gene in childhood acute lymphoblastic leukemia].
AB  - E2A gene rearrangements and E2A-PBX1 chimeric mRNA produced by t(1;19) were
      examined in 50 cases with acute lymphoblastic leukemia (ALL). Nine of 10 ALL
      cases with t(1;19) showed the rearrangement by Southern blotting using the E2A
      gene probe when digested with Xba I, Bgl II, and Eco RI, and the remaining one
      having hyperdiploidy which was considered to be a sign of good prognosis, lacked
      E2A rearrangement. Six of 7 ALL cases with t(1;19) that were tested showed the
      predicted 164 bps band of E2A-PBX1 chimeric mRNA by reverse transcriptase
      polymerase chain reaction (RT-PCR), while a case having t(1;19) without E2A
      rearrangement and 10 cases lacking t(1;19) did not. Three ALL cases tested did
      not have E2A-PBX1 mRNA at the time complete remission 4 months after diagnosis.
      Forty ALL cases lacking t(1;19), including 4 cases with t(11;19), did not reveal
      rearrangement of E2A. We conclude that t(1;19)-ALL can be molecularly diagnosed,
      and minimal residual disease could be detected by the RT-PCR method.

PMID- 8139108
TI  - [Translocation t(11;14) (q13;q32) in six patients with lymphoid malignancies of
      mature B-cell phenotype].
AB  - We described six patients with t(11;14)(q13;q32) in lymphoid malignancies. Based
      on the histologic or morphologic findings of these patients, malignant lymphoma
      diffuse large cell (ML-DL) was diagnosed in two patients, small lymphocytic (SL)
      in one, mantle zone lymphoma (MZL) in one, prolymphocytic leukemia (PLL) in one,
      and chronic lymphocytic leukemia with > 10% prolymphocytes (CLL/PL) in one. Three
      cases showed involvement of the gastro-intestinal tract, and four were leukemic.
      Five cases were dead 12 to 25 months after the time of chromosomal analysis.
      Immunological studies revealed that all the patients were positive for CD5, CD20,
      HLA-DR, and only one was weak positive for CD10. Using probe b, SstI-Sst I
      segment, Southern blot analysis showed the rearrangement of BCL-1 gene in a
      patient with MZL. Our results suggested that t(11;14) is found in lymphoid
      malignancies with mature B-cell phenotype and that hepatosplenomegaly,
      gastrointestinal involvement, leukemic manifestation, and poor prognosis are
      common clinical features.

PMID- 8139110
TI  - [Acute erythroblastic leukemia presenting as FAB M6 with surface marker positive
      for megakaryocytic and erythroid: report of a case].
AB  - A fifty five-year-old male presenting as FAB M6 had blasts that were positive
      both for erythroblastic and megakaryocytic surface makers, i.e., carbonic
      anhydrase I, CD36 and CD41. HLA-DR and cD71 were also positive. In a very small
      portion, CD33 and glycophorin A were also positive. By Giemsa staining, these
      blasts were relatively large and had basophilic cytoplasm. By electroscopic
      study, PPO was negative and showed ferritin particles, theta granules and iron
      containing mitochondria in cytoplasm. Chromosome analysis revealed major
      karyotypic abnormality (MAKA). After initial treatment with blood transfusion,
      prednisolone and exymetholone, CD41b increased in positive ratio. Trial of
      remission induction with BHAC-DMP failed and patient died in 5 months.

PMID- 8139109
TI  - [Relapse of acute leukemia after allogeneic bone marrow transplantation].
AB  - The relapses of 45 acute leukemia patients who underwent allogeneic bone marrow
      transplantation between April 1976 and February 1992 were analyzed clinically.
      The relapse rates of acute nonlymphocytic leukemia (ANLL) and acute lymphocytic
      leukemia (ALL) were 4/26 (15%) and 9/19 (47%), respectively. Although
      multivariate analysis could not be done, a high frequency of leukemia relapse was
      significantly associated with ALL, a younger age, history of extramedullary
      leukemia and blood-type identity. Chromosomal abnormalities at diagnosis,
      interval from diagnosis to bone marrow transplantation (BMT) and graft-versus
      host disease (GVHD) prophylaxis were likely to be predictive of relapse. On the
      other hand, neither stage of leukemia at BMT, acute GVHD, sex, nor WBC count at
      diagnosis was a predictive factor. Eight of 10 relapsed patients achieved
      complete remission posttransplant, but the duration of remission was only 138
      days on average. Four second BMT procedures for relapsed leukemia were carried
      out but were associated with many complications. However, one is alive well over
      6 years after the second transplantation. There is a high treatment-related
      mortality following second BMT, but there is some possibility of long survival in
      some patients.

PMID- 8139111
TI  - [Massive skeletal invasion in Hodgkin's disease observed by MRI].
AB  - A 35-year-old female developed cervical adenopathy and mediastinal tumor in 1988.
      A lymph node biopsy specimen showed nodular sclerosing Hodgkin's disease. She
      received combination chemotherapy with cyclophosphamide, vincristine, adriamycin
      and prednisolone, and radiotherapy for mediastinal tumor. She had a complete
      remission (CR). In September 1990, she developed swelling of the left hip and
      felt pain in the left hip and thigh. She also noticed swelling of the left
      inguinal lymph nodes. MRI T2-weighted images showed enlargement and destruction
      of the fascia and hyperintense signal of the left iliac and gluteus muscle. A
      biopsy specimen of the inguinal lymph node showed recurrence of Hodgkin's disease
      of mixed cellularity. She received salvage therapy with ifosfamide, methotrexate,
      etoposide and procarbazine, and achieved a second CR. The clinical appearance of
      the skeletal muscle involvement by lymphoma is uncommon, especially in Hodgkin's
      disease.

PMID- 8139112
TI  - [Reversal of myelofibrosis is an important pre-transplant factor for bone marrow
      grafting--a successful case of allogeneic bone marrow transplantation for an
      acute megakaryoblastic leukemia].
AB  - We report a successful ereated case of acute megakaryoblastic leukemia (AMKL)
      with myelofibrosis (MF), which achieved a disease free condition, with
      disappearance of MF, for over 24 months after allogeneic bone marrow
      transplantation (BMT) and summarized cases of MF receiving BMT reported in Japan
      to evaluate the influence of MF on engraftment of bone marrow (BM). A 40-year-old
      man was admitted on Jan. 29, 1991 due to anemia and thrombocytopenia. BM
      aspiration resulted in a dry tap and MF and cells stained positive with anti
      GPIIb/IIIa (CD41a) antibody were demonstrated by BM the biopsy specimen. Complete
      remission was achieved by multi-drug chemotherapy including behenoylcytosine
      arabinoside, etoposide, mitoxantrone and prednisolone (PLS). After
      preconditioning with little BU+CY, BMT was performed from an HLA-identical
      brother on Jan. 16, 1992. From day 9 of post BMT, acute skin graft versus host
      disease (grade 1) was observed, which was controlled by 60 mg/day of PSL.
      Engraftment was achieved on day 12. Although cystitis developed, he was
      discharged on Apr. 5, 1992 and remains disease free. Including the present case,
      seven allogeneic BMT patient with MF have been reported so far in Japan. Four
      cases in whom MF recovered before BMT showed better results than other three
      cases that still showed MF at BMT. Reversal of MF seems to be a favorable pre
      transplant factor for successful BMT in patients with MF.

PMID- 8139113
TI  - [Non-Hodgkin's lymphoma; initially presenting cardiac symptoms].
AB  - Two long surviving cases of cardiac lymphoma are reported. The first case was an
      83-year old man with complete A-V block, congestive heart failure, and pleural
      effusion. Echocardiography revealed a widespread tumor from the right ventricular
      wall to the inner space. Cytological examination of pleural effusion showed B
      cell type lymphoma. He was treated with systemic chemotherapy and achieved
      partial remission, continuing for more than 12 months. The second case was a 50
      year old man with superior vena cava syndrome caused by a cardiac tumor occupying
      the whole right atrium. He was treated with partial resection of the tumor and
      pathological examination showed B-cell type lymphoma. Then he was treated with
      systemic chemotherapy for massively residual lymphoma, and achieved partial
      remission, continuing for more than 20 months. Both cases are in good condition
      under maintenance chemotherapy. In general, malignant lymphoma which is initially
      presenting cardiac symptoms (so called "cardiac lymphoma") is not so frequent to
      diagnose premortally, and its prognosis is poor because of delay of diagnosis due
      to the location of tumor. In addition, insufficient chemotherapy to avoid cardiac
      rupture or embolism of the pulmonary artery also tend to make the prognosis poor.
      Recently, several successful cases of cardiac lymphoma treated with systemic
      chemotherapy have been reported owing to the progress an diagnostic techniques,
      including echocardiography, CT scan, Ca-scintigraphy and MR imaging. Our
      experience also indicated that early diagnosis and intensive systemic
      chemotherapy can obtain long survival in cases of cardiac lymphoma.

PMID- 8139114
TI  - [Acute monoblastic leukemia (M5a) with dysmegakaryocytopoiesis associated with
      t(16;21) (p11;q22)].
AB  - We report a 24-year-old woman who had acute monoblastic leukemia associated with
      t(16;21) (p11;q22). She was referred to our hospital in April 1992 because of
      high fever and hemorrhagic diathesis. Physical examination on admission showed no
      hepatosplenomegaly. The hemoglobin was 5.1g/dl, platelet count 1.7 x
      10(4)/microliters, the white blood cell count 18,700/microliters. Bone marrow
      aspirate showed that 86% of nucleated cells were monoblasts which were positive
      for peroxidase and alpha-naphtyl butyrate esterase. She was diagnosed as having
      M5a. Dysmegakaryopoiesis, such as micromegakaryocytes and megakaryocytes with
      multiple small separated nuclei, was seen in the bone marrow. Chromosomal
      analysis revealed t(16;21). Complete remission was achieved after two courses of
      BHAC-DMP therapy, but dysmegakaryopoietic features remained. She relapsed in
      September 1992. Review of the literature and this patient indicate that acute
      nonlymphocytic leukemia with t(16;21) is associated with multilineage leukemic
      differentiation.

PMID- 8139115
TI  - [Three cases of hematologic malignancies with jumping translocation].
AB  - We treated three cases of hematologic malignancies (Burkitt's lymphoma, ALL (L3),
      AML (M0)) with jumping translocations. Tumor formation was easily occurred in all
      three cases. The location of the jumping translocation was 1q21 in all three
      cases. Hematologic malignancies with jumping translocation tend to be B-cell
      lineage and have poor prognosis. The significance of jumping translocation is
      unknown yet, but it seems that jumping translocation is related to the tumor
      progression, rather than tumorigenesis. So that the intensive therapy including
      bone marrow transplantation must be considered.

PMID- 8139116
TI  - [Allogeneic bone marrow transplantation for two patients with acute myeloid
      leukemia with trilineage myelodysplasia (T-MDS)].
AB  - Case 1: A 26-year-old female was admitted because of leukocytosis with 43.6%
      myeloblasts and 33.6% monocytes, and trilineage myelodysplasia (T-MDS) was
      detected on bone marrow (BM) smear. She was diagnosed as having acute myeloid
      leukemia (AML) (M4) with T-MDS and was treated with the Japan Adult Leukemia
      Study Group (JALSG) AML87 protocol. After completion of chemotherapy, leukemic
      myeloblasts remained minimally and myelodysplastic changes were still detected on
      BM smear. She underwent allo-BMT from an HLA-identical sibling. The conditioning
      regimen consisted of busulfan and cyclophosphamide. Cyclosporine A and short term
      methotrexate were administered prophylactically for graft-versus-host disease
      (GVHD). She developed slight veno-occlusive disease and pancytopenia, which
      improved soon. She is surviving free of disease for 37 months from BMT. Case 2: A
      41-year-old male was diagnosed as having T-MDS AML (M2) and achieved complete
      remission with the AML89 protocol, but relapsed soon. He underwent allo-BMT from
      an HLA-identical sibling. The conditioning regimen and prophylaxis against GVHD
      were the same as in case 1. He developed mild acute GVHD, pleural effusion and
      later mild chronic GVHD. These improved soon. He is surviving free of disease for
      21 months from BMT. Some reports suggest that intensive chemotherapy can induce
      CR in 40%-70% of patients with T-MDS AML, but most of them tend to relapse and
      rarely survive long. We consider that the best strategy for treatment of T-MDS
      AML is allo-BMT at present, if suitable donors are available.

PMID- 8139117
TI  - [Adult T cell leukemia with cytomegalovirus associated hemophagocytic syndrome].
AB  - A 59-year-old woman, diagnosed as adult T-cell leukemia (ATL), was admitted
      because of fever and disturbance of consciousness. Peripheral blood examination
      demonstrated leukopenia and anemia, and subsequently thrombocytopenia. Bone
      marrow aspiration showed the increase of mature histiocytes with hemophagocytosis
      and a diagnosis of hemophagocytic syndrome (HPS) was established. She died due to
      respiratory failure on the eighth hospital day. Autopsy histological examination
      revealed systemic cytomegalovirus (CMV) infection with CMV pneumonia, and also
      demonstrated the findings of HPS in bone marrow, lymph nodes, and spleen. This
      case was considered as virus associated hemophagocytic syndrome (VAHS) developed
      by CMV infection. CMV is one of the causative viruses of VAHS and the
      opportunistic infection. In the patient with ATL in the immunodeficiency state,
      VAHS accompanied with opportunistic infection might be one of the causes of
      pancytopenia.

PMID- 8139118
TI  - [Acute promyelocytic leukemia (APL) resulting in broad cerebral infarction during
      all-trans retinoic acid (ATRA) treatment].
AB  - A 27-year-old woman visited Kanto Teishin Hospital complaining of fever and
      petechiae in September, 1992. Her fetus had suddenly died in the uterus two weeks
      before (in the sixth month of pregnancy). Total white blood cell (WBC) count was
      3.2 x 10(3)/microliters with 80% promyelocytes. Bone marrow was hypercellular
      with 90% promyelocytes. Disseminated intravascular coagulation (DIC) was
      recognized. She was diagnosed as having acute promyelocytic leukemia (APL), and
      treatment with daily oral administration of all-trans retinoic acid (ATRA) (70
      mg/body/day) was begun. On day 4, hemiplegia and aphasia appeared. Broad cerebral
      infarction was suspected from computed tomography. On day 9, the WBC count
      increased rapidly, standard chemotherapy was added and she achieved complete
      remission. ATRA is known to have stimulatory effects on the differentiation of
      APL cells, but some reports have described thromboembolic events during the
      administration of ATRA. In this case, ATRA might have affected coagulability
      resulting in cerebral infarction.

PMID- 8139119
TI  - [Extramedullary pleural myelo-megakaryoblastic crisis during hematological
      chronic phase in chronic myeloid leukemia].
AB  - A 77-year-old man, in whom chronic myeloid leukemia (CML) had been diagnosed in
      October 1990, was admitted to hospital with right chest pain in November 1992.
      Bone marrow examination revealed the chronic phase of CML. Chest X-ray showed
      right pleural effusion. The cells from pleural effusion were positive for CD7,
      CD13, CD33, CD41a, including CD33, CD41a-double positive cells in 57.5%. Southern
      blot analysis revealed 3'bcr rearrangement. Electron microscopic examination
      showed the presence of platelet peroxidase. An abnormal karyotype with various
      additional chromosomes was observed. This is a rare case of extramedullary
      pleural myelo-megakaryoblastic biphenotypic crisis during the chronic phase of
      CML.

PMID- 8139120
TI  - [Progress of preoperative diagnosis of pancreatic tumor--with special reference
      to extension of pancreatic cancer].
AB  - Preoperative diagnosis of the extension of pancreatic cancer is very important
      for determining the range of resection. We evaluated the preoperative imaging
      diagnosis of the tumors and compared it with the pathological diagnosis. Out of
      68 pancreatic head cancers, the percentage of correct diagnosis of serosal
      invasion was 69.1%, that of over-estimate was 23.5% and that of under-estimate
      was 7.4%. In the case of retroperitoneal invasion, a correct diagnosis had been
      made in 79.1%, over-estimate in 4.5% and under-estimate in 16.4%. In the case of
      portal vein invasion, these percentages were 52.8%, 39.6% and 7.5%, respectively.
      In the case of lymph node involvement, these percentages were 85.3%, 2.9% and
      11.8%, respectively. The percentage of preoperative over-estimate was higher for
      serosal invasion and that of preoperative under-estimate was higher for
      retroperitoneal invasion. In the case of portal vein invasion, the percentage of
      preoperative over-estimate was relatively high. Of the 12 patients who had
      paraortic lymph node metastases, 6 patients had a single metastatic node in the
      paraortic area. The minimum size of these nodes was 2 x 2 mm. Only 5 cases could
      be diagnosed preoperatively. We evaluated the usefulness of abdominal CT scan and
      superior mesenteric arteriography for the diagnosis of superior mesenteric
      arterial wall invasion. In both methods, the over-estimate rate was 0%, but the
      under-estimate rate was relatively high. Conclusively the preoperative diagnosis
      of the extension of the pancreatic cancer by conventional imaging methods has
      some limits.

PMID- 8139121
TI  - [Recent advances in imaging diagnosis of pancreatic neoplasma with special
      reference to early diagnosis of the cancer].
AB  - Recent advance in various diagnostic imagings has enabled the early diagnosis of
      pancreatic tumors. In pancreatic cancer, the tumor-demonstrability by US, CT, and
      MRI has reached 80% in the recent 6 years, which is superior to the rate in the
      past decade from 1978 and 1987. However, the prognosis of pancreatic cancer is
      still poor even if the cancer can be resected. To improve the outcome of surgical
      intervention, early detection of small cancers (< or = 2 cm in diameter) and
      appropriate intervention based on preoperative diagnosis of the tumor extension
      are proposed. The tumor detectability of small pancreatic cancer by US, CT, MRI
      was 67%, 25%, 20%, respectively, and thus US was the most valuable tool. In the
      prediction of tumor extension of serosal invasion (S factor), retroperitoneal
      invasion (Rp factor) and vessel invasion (PV factor), both US and CT were
      efficacious with an accuracy of more than 70%. In conclusion, recently-advanced
      imaging seems to be useful for detecting a small pancreatic cancer and evaluating
      the tumor extension, but it remains difficult to diagnose a carcinoma in situ; a
      truly early cancer.

PMID- 8139122
TI  - [Diagnosis of the pancreatic diseases by intraductal ultrasound of the pancreas-
      with special reference to clinical cases difficult to diagnose differentially
      pancreatic diseases by the endoscopic retrograde pancreatography].
AB  - We examined the usefulness of the intraductal ultrasound (IDUS) examinations by
      comparing the IDUS images with the endoscopic retrograde (ER) pancreatograms. We
      inserted an IDUS probe with 30 MHz at frequency transpapillary into the main
      pancreatic duct (MPD) in 105 cases with pancreatic diseases (30 cancers, 30 mucin
      producing tumor, 3 islet cell tumor, 1 pancreatic serous cyst adenoma, 1
      pancreatic teratoma, 1 pancreatic solid and cystic tumor and 39 chronic
      pancreatitis). All 105 cases were performed ER pancreatography. Sixty-four of 105
      cases (22 cancers, 20 mucin-producing tumor, 3 islet cell tumor, 1 pancreatic
      serous cyst adenoma, 1 pancreatic teratoma, 1 pancreatic solid and cystic tumor
      and 16 chronic pancreatitis) were operated and the IDUS images were compared with
      the corresponding histopathological sections. The usefulness of the IDUS
      examinations of the pancreatic diseases were the following cases; differential
      diagnosis between benign and malignant cases with localized stenosis of the MPD,
      differential diagnosis of the cases with displacement of the MPD, and the
      diagnosis of the intraductal extent and of invasion of the tumor in the mucin
      producing tumor of the pancreas with the dilation of the MPD. IDUS examinations
      are performed by the IDUS probe with high frequency, so the indications of the
      IDUS examinations are to detect the small lesions in the pancreas.

PMID- 8139123
TI  - [Clinicopathological features and diagnostic points of uncommon pancreatic
      tumors].
AB  - Clinicopathological features of uncommon pancreatic tumors including solid cystic
      tumor (SCT), acinar cell carcinoma and pancreatoblastoma are described, based
      upon a literature survey and own experiences. They are often discovered by US and
      CT as asymptomatic pseudocystic tumor. SCTs almost always occur in young female
      and Pancreatoblastoma, in children less than five years old. The prognosis is
      very favorable in SCT, and relatively good in acinar cell carcinoma and
      pancreatoblastoma. Pancreatoblastoma is often associated with the elevation of
      serum AFP levels. Characteristic histological features and immunocytochemical
      features are also described, all of which are very different from those of usual
      pancreatic ductal carcinoma. Molecular biological features including the results
      of k-ras and p53 point mutation are also discussed. In addition to the
      clinicopathological features, these uncommon tumors are very different from usual
      ductal carcinoma in the molecular biological features.

PMID- 8139124
TI  - [Diagnosis and surgical treatment for endocrine tumors of the pancreas].
AB  - Clinical features, diagnostic accuracy of imaging study, and the outcome of
      surgical treatment for endocrine tumors of the pancreas were analyzed in 12
      patients who underwent surgery for the past 16 years and 11 months. The 12 cases
      were classified into two groups: functioning tumors in 8 (insulinoma in 7
      including one malignant case, and malignant glucagonoma in one), and
      nonfunctioning tumors in 4 including 3 malignant cases. In functioning tumors,
      tumor size was 2 cm or less in 6 benign cases, but 5 cm or more in 2 malignant
      cases. In nonfunctioning tumors, tumor size was larger, ranging from 3.5 to 8.0
      cm. Diagnostic accuracy for localization of functioning tumors was 66.7% for US,
      75.0% for CT, 66.7% for endoscopic retrograde pancreatography (ERP), and 50.0%
      for selective angiography, while all nonfunctioning tumors could be detected by
      any diagnostic imagings. Percutaneous transhepatic portal venous sampling for
      immunoreactive insulin was very helpful to localize insulinoma. Stenosis or
      obstruction of the main pancreatic duct on ERP and arterial encasement on
      angiography highly suggested a malignant tumor. Even for malignant cases with
      liver metastasis, resection of the primary tumor with debulking of metastatic
      disease or intraarterial infusion chemotherapy was considered to prolong patient
      prognosis.

PMID- 8139125
TI  - [Detection of mycobacterial DNA by polymerase chain reaction method].
AB  - All published primers and lysis methods were introduced and briefly reviewed
      herein. Many different polymerase chain reaction procedures were described for
      the detection of mycobacteria in sputum. Most of these published methods were not
      satisfactory to detect mycobacteria in clinical specimens. We established a
      sensitive method to extract mycobacterial DNA in the sputum. First, we treated
      sputum with Sputazyme, and then with lysozyme. Then mycobacterial DNA was
      extracted by phenol extraction, beads disruption, or alkaline SDS extraction
      method. This lysozyme pre-treatment marked increased the sensitivity of the PCR
      reaction.

PMID- 8139126
TI  - [Evaluation for serum apolipoproteins in patients with diabetes mellitus].
AB  - Six fractions of serum apolipoproteins (apolipoprotein A-I, A-II, B, C-II, C-III
      and E) obtained from 100 patients with diabetes mellitus not administered any
      antihyperlipidemic drugs were measured to clarify the relationship between
      diabetes mellitus and the abnormal lipidosis. The serum concentrations of
      apolipoprotein B, C-II and C-III were significantly higher in these diabetics
      than in the controls (p < 0.05), and that of apolipoprotein E was significantly
      lower (p < 0.01). The serum concentrations of apolipoprotein C-II, C-III and E (p
      < 0.05) as well as HbA1C and FRA (p < 0.001) were significantly higher in the
      insufficient control group (FPG > or = 140 mg/dl) of diabetes mellitus. The serum
      concentrations of apolipoprotein C-II, C-III and E were significantly higher in
      the treated groups (p < 0.05). The serum concentrations of apolipoprotein B, C
      II, C-III and E were significantly higher (p < 0.01) in the high cholesterol
      group (> 220mg/dl) and the high triglyceride group (> 150mg/dl) among the
      diabetic groups, but no significant differences were observed in the
      concentrations of apolipoprotein A-I and A-II.

PMID- 8139127
TI  - [Detection of antineutrophil cytoplasmic antibodies in sera from patients with
      rheumatoid arthritis by indirect immunofluorescence technique].
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from 52 patients with
      rheumatoid arthritis (RA), including 9 patients with malignant RA (MRA) and 20
      healthy controls were examined by indirect immunofluorescence technique (IIF).
      Nine out of 52 RA patients showed positive ANCA staining. None of MRA patients
      had, however, ANCA in sera. The staining pattern for ANCA was either perinuclear
      for 4 sera or non-specific for 5 sera, but not cytoplasmic. Furthermore, anti
      nuclear antibodies (ANA) in 9 ANCA positive RA sera were tested by IIF, using Hep
      2 cells. Six sera had positive ANA. Three sera showed as nucleolar and 1 serum as
      centromere in ANA staining pattern. The incidence of these ANA staining pattern
      in ANCA positive sera (4 out of 9) was higher than in ANCA negative sera (1 out
      of 19). The clinical profiles and laboratory findings of 9 RA patients with
      positive ANCA revealed that they had suffered and treated for more than 10 years
      and had still active joint inflammation, like intractable RA. These results
      indicate that ANCA in RA are not associated with vasculitis.

PMID- 8139129
TI  - [Study on decision support system for the interpretation of laboratory data by an
      artificial neural network--with a special reference to estimation for
      histological diagnosis of liver diseases with laboratory data on liver function].
AB  - An artificial neural network (ANN) was trained on laboratory data of liver
      function tests to estimate for histological diagnosis in patients with liver
      diseases such as chronic hepatitis, liver cirrhosis and fatty liver. ANN
      diagnosed accurately 95.3% of the cases for training and 50% of the test cases.
      Elimination of ZTT, GOT or A/G ratio from the data set for input reduced the
      ability of accurate diagnosis, whereas elimination of TBA raised this ability to
      66.7%. On the other hand, accuracy of physician in diagnosing the test cases
      ranged from 20.8 to 62.5%. From our results it is expected that ANN may support a
      physician's decision on the interpretation of laboratory data.

PMID- 8139128
TI  - [An improved method for determination of C-peptide levels in serum: pretreatment
      of test samples with anti-insulin antibody insolubilized with magnetic
      particles].
AB  - RIA using anti-C-peptide antibody has been employed for determination of C
      peptide in serum. However, the level by this method is a sum of the levels of C
      peptide and proinsulin, because anti-C-peptide cross-reacts with proinsulin. This
      time we developed an improved assay for C-peptide, in which a test sample is
      pretreated with anti-insulin antibody to eliminate proinsulin in samples before C
      peptide assay. The assay procedure is composed of 3 steps; the first is the
      incubation of test serum with anti-insulin antibody insolubilized with magnetic
      particles to form a complex of proinsulin-anti-insulin antibody, the 2nd step is
      the centrifugation of the mixture to eliminate the complex and the last step is
      the assay for C-peptide by use of RIA kit in the supernatant. The assay is
      simple, sensitive and reproducible. Serum C-peptide level by this method is not
      influenced by the presence of proinsulin in test serum, even when as high as 9
      ng/ml of proinsulin is contained. This assay revealed that a patient with
      insulinoma had normal level of serum C-peptide in spite of the extremely high
      level of proinsulin.

PMID- 8139130
TI  - [Determination of globin synthesis studies using high performance liquid
      chromatography technique].
AB  - In vitro globin chain synthesis ratios (beta/alpha) were determined using high
      performance liquid chromatography (HPLC) in twenty-five alpha or beta
      thalassemiaes as well as six normal controls. Among thalassemiaes nineteen were
      Japanese and six Korean. Two kinds of cation exchange columns.; Mono S, HR 5/5 by
      Pharmacia and TSK gel by Tohso were compared. Hemolysates (10%), in stead of
      purified globin peptides, were directly subjected to the both columns, and 3H
      labeled globin chain in vitro synthesized were separated on them. The Tohso
      column gave better resolution of globin peptides, resulting in sharp elution
      profiles. The HPLC system took about two hours for an analysis of a sample. In
      contrast, the conventional carboxymethyl cellulose (CMC) chromatography by Clegg
      need larger sample amounts for globin extraction and twenty-four hours to be
      completed. The HPLC is evidently simple and rapid. The globin chain ratios thus
      obtained by HPLC were 1.04-1.08, 0.23-0.89, 1.22-1.62 and 2.05-4.29 for normals,
      thirteen beta-thalassemia minors, seven alpha-thalassemia traits and three Hb H
      diseases respectively.

PMID- 8139131
TI  - The role of novel 30-kD protein in human podocytes: special relevance to
      proteinuria in glomerulonephritis.
AB  - A new monoclonal antibody (MAb) was raised against human glomerular components to
      investigate the possible existence of glomerular antigens reflecting cellular
      adaptation in glomerulonephritis. The MAb recognized a podocyte antigen as well
      as those expressed on renal arterial endothelial cells and smooth muscle cells by
      indirect immunofluorescence. An additional, but weaker immunoreaction was found
      in epithelial cells of the Bowman's capsule. This MAb recognized a 30-kD protein
      on western blotting of glomerular extracts under non-reducing and reducing
      conditions. Immunoperoxidase electron microscopy revealed that this antigen is
      present within the cytoplasm, but not on the cell membrane of the podocytes.
      Moreover, the antigen was found to be reduced in the glomeruli of patients with
      minimal change glomerulonephritis. These results suggest that the 30-kD protein
      is a novel protein, which we hypothesize is involved in maintenance of the
      structural and functional integrity of the podocytes. In addition, reduced
      expression of the 30-kD protein in the podocytes may be related to the increasing
      proteinuria in minimal change glomerulonephritis.

PMID- 8139132
TI  - A kinetic study of the glomerular cells of developing and mature rat kidneys
      using an anti-bromodeoxyuridine monoclonal antibody.
AB  - Newborn and mature Wistar rats received a single intraperitoneal injection of 5
      bromo-2'-deoxyuridine (BrdU), a DNA precursor, to assess cellular proliferation
      by labeling S-phase cells. For immunohistochemical analysis, paraffin sections
      were prepared two hours after BrdU injection. The various stages of development
      of the glomeruli were observed within each newborn rat. The most primitive
      glomeruli were found close to the renal capsule, with progressively more mature
      glomeruli appearing in the deep renal cortex. BrdU-positive nuclei were
      frequently detected in the epithelia of nephrogenic vesicles, S-shaped vesicles
      and ureteral buds. When the capillaries invaded the S-shaped vesicles, the
      developing glomerular basement membrane was recognizable. In this and more mature
      stages of the glomeruli, presumptive podocytes no longer showed BrdU-positive
      nuclei, but they were easily detected in the mesangial and endothelial cells of
      the glomerular tufts. The mean labeling index of the glomerular tuft cells of
      mature rats was approximately 0.54%. The majority of labeled cells in the
      glomerular tufts were endothelial cells. Mesangial cells had a low labeling
      index. Podocytes revealed no evidence of proliferation. The labeling index of
      Bowman's epithelial cells, however, was approximately 0.71%, higher than that of
      the tuft cells. These findings may contribute to a better understanding of the
      mechanisms of cellular interplay within the glomeruli.

PMID- 8139133
TI  - Studies on the glomerular permeability with human liver ferritin.
AB  - To clarify the roles of the glomerular basement membrane (GBM) in filtration
      mechanisms, human liver ferritin was used for the first time as a tracer. Urinary
      excretion of human liver ferritin was measured and the injected ferritin was
      tracked under electron microscopy. Puromycin aminonucleoside (PAN) nephrosis was
      induced in Sprague Dawley rats and normal saline was injected into control rats.
      Monomeric and polymeric human ferritin were isolated from post mortem samples.
      Both kinds of human liver ferritin were injected into the experimental and
      control rats and urine samples were examined for human ferritin by
      radioimmunoassay. Rats with PAN nephrosis excreted approximately 33 times more
      monomeric ferritin than the controls. Appreciably more monomeric ferritin was
      excreted than polymeric ferritin. In control rats, monomeric ferritin particles
      were restricted in the lamina rara interna and inner aspect of the glomerular
      basement membrane 30 min after injection. On the other hand, in rats with PAN
      nephrosis, monomeric ferritin particles were seen throughout the width of the GBM
      and in the epithelial cells. With human liver ferritin, we were able to
      demonstrate the escape of the ferritin into the urine in addition to conducting
      the conventional electron microscopic tracer study of the glomerular capillary
      wall. Human liver ferritin shows potential as a useful tracer in the study of
      glomerular permselectivity.

PMID- 8139134
TI  - Erythrocyte sodium cannot predict hypotensive effects of calcium channel
      blockers.
AB  - Antihypertensive efficacy of the calcium channel blocker, nilvadipine, was
      investigated in 21 patients with essential hypertension in relation to the
      intracellular sodium concentration ([Na]i) in erythrocytes and clinical
      variables, such as age, body weight, pretreatment blood pressure and plasma renin
      activity. Dihydropyridine nilvadipine reduced mean blood pressure from 120 +/- 6
      to 106 +/- 8 mmHg (p < 0.01). The hypotensive effect of nilvadipine was
      positively correlated with age (r = 0.67, p < 0.01) and inversely correlated with
      plasma renin activity (r = -0.62, p < 0.01), but was not correlated with
      erythrocyte [Na]i or any other indices. Erythrocyte [Na]i was decreased with
      nilvadipine treatment (8.27 +/- 1.69 to 7.97 +/- 1.49 mM, p < 0.01). However, no
      link was found between the change in [Na]i and the hypotensive effect of the
      drug. In conclusion, the antihypertensive efficacy of nilvadipine was predictable
      by age and renin status, but not by erythrocyte [Na]i. A significant role of
      reduction of [Na]i in the hypotensive effect of the calcium channel blockers was
      not detected.

PMID- 8139135
TI  - Pharmacokinetic study of recombinant human erythropoietin treatment in pre
      dialysis end stage renal disease patients.
AB  - We treated pre-dialysis ESRD patients with recombinant human erythropoietin
      (rHuEPO) by either the subcutaneous (s.c.) or intravenous (i.v.) route, and
      investigated the pharmacokinetics of rHuEPO. Twenty patients were divided equally
      into two groups by the difference in route, and rHuEPO was administered once per
      week for 8 weeks. The dose was 3,000 and 6,000 IU in the s.c. group and 3,000,
      6,000 and 9,000 IU in the i.v. group. Although anemia was corrected significantly
      in both groups, residual renal function was not affected significantly.
      Pharmacokinetic study revealed that none of the parameters changed between the
      initial and final treatments in any of the groups. Area under the curve (AUC) and
      maximum concentration (Cmax) was consistently smaller in the s.c. --than in the
      i.v.--treated group. Mean residence time (MRT) was 3 times longer in the s.c.
      group than in the i.v. group. Bioavailability of rHuEPO in the s.c. group was
      around 35%, and mean absorption time (MAT) was around 25 hours. Though the s.c.
      route has been reported to be more effective for correcting anemia with rHuEPO
      than the i.v. route when rHuEPO was administered either twice or three times per
      week, our study demonstrated that the effect of rHuEPO was almost equal between
      the s.c.-treated and i.v.-treated groups when rHuEPO was administered once per
      week. We assume that this equivalent degree of efficacy in the s.c. group in
      spite of low values of AUC and Cmax might be derived by the longer MRT. Thus, we
      consider that MRT is an important factor and the efficacy of rHuEPO should be
      investigated with evaluation of MRT when the administration route is different.

PMID- 8139136
TI  - Pravastatin administration to hyperlipidemia in patients with nephrotic syndrome.
AB  - We treated hyperlipidemia in patients with nephrotic syndrome (NS) using
      pravastatin for more than one year. There were 7 cases consisting of 3 with
      minimal change nephrotic syndrome (MCNS), 1 with focal glomerulosclerosis (FGS),
      1 with proliferative glomerulonephritis (PGN), 2 with membranous
      glomerulonephritis (MGN) and 1 of unknown origin. Three cases consisted of
      frequent relapsers, and 4 were steroid-resistant. Six randomly selected age- and
      sex-matched nephrotic patients were used as controls. The daily excretion of
      proteinuria was not decreased after pravastatin treatment, but, the serum albumin
      rose from 3.1 +/- 1.1 to 3.4 +/- 1.0 mg/dl. The serum total cholesterol level was
      significantly reduced from 401 +/- 174 mg/dl to 331 +/- 103 mg/dl in spite of an
      absence of marked change in the control group. However, there were no significant
      changes in the triglyceride and lipoprotein levels. The atherogenic index was 7.1
      +/- 3.7 before and 2.8 +/- 1.7 after pravastatin treatment, respectively.
      Improvement of renal function defined by delta decrement of renal function per
      year (0.08 +/- 0.06 vs. 0.12 +/- 0.26) was observed after the discontinuation of
      pravastatin administration in 3 out of 4 intractable cases. We conclude that
      pravastatin has a potent effect in reducing the serum level of total cholesterol,
      but not triglyceride in NS. Furthermore, pravastatin can induce renal dysfunction
      especially in patients with intractable nephrotic syndrome.

PMID- 8139137
TI  - The effect of enalapril on proteinuria in patients with chronic
      glomerulonephritis and renal insufficiency.
AB  - We evaluated the effect of enalapril on proteinuria in 20 patients with chronic
      glomerulonephritis (CGN) and renal insufficiency. Patients were accepted into the
      study according to the following criteria: 1) a serum creatinine (s-Cr) level
      over 1.5 mg/dl or a creatinine clearance (Ccr) under 70 ml/min; and 2) urinary
      protein (UP) over 1.0 g/day, expect for the cases with uncontrollable
      hypertension. We measured total protein (TP), albumin, s-Cr, Ccr, UP, and Ht
      during the elanapril therapy. After enalapril therapy, UP slowly decreased, and
      TP and albumin levels increased. The levels of s-Cr and Ccr did not vary. None of
      the patients required discontinuation of enalapril therapy caused by side
      effects, such as anemia or hyperkalemia. In conclusion, enalapril has the effect
      of decreasing in proteinuria and increasing TP and albumin in patients with CGN
      and renal insufficiency irrespective of the original diseases.

PMID- 8139138
TI  - Clinical significance of hypocitraturia in kidney stone patients.
AB  - Although a low concentration of urinary citrate is cited as one of the risk
      factors promoting stone formation or recurrence among patients with urinary
      stones, its clinical significance remains obscure. We studied 62 kidney stone
      patients with a low urinary citrate excretion (hypocitraturia) of less than 320
      mg/day, without any apparent cause. The incidence of hypocitraturia in 722 kidney
      stone patients followed up at our stone clinic was 14.6%. Among the 62 patients,
      37 had an uncomplicated hypocitraturia as the sole abnormality, while 25 had
      other associated stone risk factors, including hypercalciuria in 11% (7/62),
      hyperuricosuria in 24% (15/62), hyperoxaluria in 5% (3/62) and hypomagnesuria in
      24% (15/62). The rate of urinary stone recurrence was 38% (14/37) in
      uncomplicated hypocitraturia, and 52% (13/25) in complicated hypocitraturia, but
      no statistical difference was observed. Regarding the outcome of stones, more
      stones were managed with lithotripsy and more passed spontaneously in the
      hypocitraturic patients than in the control patients with normal urinary citrate
      excretion. The diagnosis of hypocitraturia complicated with additional stone
      risks urged us to treat patients more vigorously with lithotripsy and medication,
      resulting in a prompt cure.

PMID- 8139139
TI  - A case of nephrotic syndrome associated with hepatic glomerulosclerosis and
      diabetic nephropathy.
AB  - We report here an adult case of nephrotic syndrome associated with hepatic
      glomerulosclerosis with the hepatitis C virus (HCV) antigen and diabetic
      nephropathy. To clarify the etiology of the nephrotic syndrome, we performed a
      renal biopsy and obtained the histological findings of hepatic
      glomerulosclerosis, glomerular mesangial cell proliferation and mesangial
      expansion. Electron dense deposits and deposits of IgA and C3 were also noted in
      the glomerular mesangial areas. Histological findings of diabetic nephropathy
      included thickening of the glomerular basement membrane and aneurysmal change of
      glomerular capillary walls in light microscopy. In immunofluorescence, linear
      staining of IgG was observed in the glomerular capillary walls, Bowman's capsules
      and tubular basement membranes. HCV was also detected focally in the glomerular
      capillary walls by immunofluorescence. Association of these two diseases has not
      been reported in any of the previous manuscripts that we reviewed. Thus, this
      patient seems to be a case of very rare association of the two diseases.

PMID- 8139140
TI  - Waldenstrom's macroglobulinemia associated with amyloidosis and membranous
      nephropathy.
AB  - A 61-year-old man with massive proteinuria and hyper gamma-globulinemia was
      admitted to hospital because of massive edema and pulmonary infection. He showed
      significantly high level of serum IgM (3244 mg/dl) with lambda-type M-protein and
      Bence Jones protein detected by immunoelectrophoresis. Renal biopsy specimen
      showed not only the diffuse amorphous amyloid deposition in mesangial area but
      global thickening of capillary wall with spike formation by silver staining which
      was similar to the spicular formation. Immunofluorescence disclosed find granular
      deposition of IgG and C3 along the capillary wall and the electromicroscopic
      findings clearly showed both massive amyloid fibril at mesangial area and diffuse
      epimembranous electron dense deposits. lambda-type Bence Jones protein in
      macroglobulinemia was suggested not only the cause of renal amyloidosis but also
      the antigenic origin of membranous nephropathy in this case.

PMID- 8139141
TI  - A case of xanthogranulomatous pyelonephritis in a child.
AB  - We report an additional case of histopathologically confirmed xanthogranulomatous
      pyelonephritis in a 9-year-old boy. He was admitted to hospital with a two-day
      history of sustained fever. Physical examination revealed tenderness in the right
      upper quadrant of the abdomen. Results of a complete blood count and serum
      biochemical investigations showed slight anemia and positive C reactive protein.
      Culture of urine failed to grow any bacteria. Excretory urography revealed
      deformity of the right renal calyces. Computed tomography showed a focal area of
      low density in the right kidney. Nephrectomy was carried out as fever had been
      sustained despite intensive treatment with antibiotics. Sectioning revealed that
      the renal parenchyma had been replaced by a butter yellow nodule, which was
      histopathologically confirmed as xanthogranulomatous pyelonephritis. This is the
      nineteenth reported case in children in Japan to our knowledge.

PMID- 8139142
TI  - Two forms of acidic arginine amidases in human kidney.
AB  - Two forms of acidic arginine amidases were separated from human kidney extract
      using the techniques of basic ion exchange adsorption and elution as well as lima
      bean trypsin inhibitor (LBTI) and aprotinin affinity adsorptions and elutions.
      The enzymes were tentatively named acidic human renal arginine amidase-L (AHRAA
      L, with affinity to an LBTI column) and -A (AHRAA-A, with affinity to an
      aprotinin column). Both enzymes showed a similar molecular mass of approximately
      3.0 x 10(4) daltons, differing from that of human renal kallikrein (HRK,
      molecular mass of 4.8 x 10(4) daltons). The specific activity of AHRAA-L and -A
      were 106 and 680 nmol/min/A280 of Val-Leu-Arg-pNA amidolysis, respectively, and
      they were strongly inhibited by LBTI and human urinary trypsin inhibitor (UTI),
      while ethylenglycol-bis(beta-amino ethylether)-N,N,N',N'-tetraacetic acid (EGTA)
      showed a weak or no effect on both enzymes.

PMID- 8139143
TI  - [Study of nephrotoxicity through glutathione metabolism by cisplatin (CDDP) and
      adriamycin (ADM) in rat kidneys].
AB  - We studied cytotoxicity in vitro through reduced glutathione (GSH) metabolism by
      cisplatin (CDDP) and adriamycin (ADM) in rat kidneys. Renal cortical slices of
      Fischer 344 rats were incubated with Krebs-Ringer buffer containing CDDP (0-5mM)
      or ADM (0-0.5 mM). GSH and glutathione reductase (GSSG reductase) in these renal
      cortical slices were determined. Cell viability was assessed by lactate
      dehydrogenase (LDH) leakage. The following results were obtained. 1)
      Intracellular GSH in renal cortex was decreased by CDDP dose- and time
      dependently. 2) The activity of GSSG reductase was suppressed by CDDP, but not by
      ADM. 3) LDH leakage increased significantly with CDDP and ADM respectively. 4)
      The incubation of renal cortical slices with GSH exogenously protected the
      increase of LDH leakage induced by CDDP or ADM. 5) The coincubation of renal
      cortical slices with CDDP and ADM did not increase LDH leakage compared with
      single administration of ADM. 6) LDH leakage in incubation with ADM after
      incubation with CDDP increased remarkably. The viability of renal cortical slices
      was more damaged by ADM under the condition of depleted GSH by CDDP. Therefore,
      it seemed that the order of administration was very important in combination
      chemotherapy.

PMID- 8139144
TI  - [Effect of recombinant atrial natriuretic peptide (r-ANP) on ischemic and
      cyclosporine-induced kidney damage in rats].
AB  - Cyclosporine A (CYA) a new immunosuppressive drug, has greatly improved the
      outcome of solid graft transplantation. The nephrotoxicity of CYA, however, is a
      serious problem, and constitutes the major obstacle limiting the use of CYA as an
      immunosuppressive agent for renal transplantation. On the other hand, the newly
      described atrial natriuretic peptide (ANP) hormonal system in both humans and
      animals appears to play an important role in sodium and water excretion. The
      present study examined the nephrotoxicity of CYA and the effect of recombinant
      ANP (r-ANP) on the damaged kidneys in three groups. Group 1 consisted of rats
      with 45 minutes warm ischemic left kidney and right nephrectomy [WI rats]; Group
      2 consisted of WI rats with oral administration of CYA (100mg/kg/day) for 2 weeks
      [WI+CYA rats]; Group 3 consisted of WI+CYA rats with intraperitoneal
      administration of r-ANP (10ng/kg/day) for 2 weeks. Group 2 had lower glomerular
      filtration rates (GFR) and renal plasma flow (RPF) than Group 1, but Group 3 had
      significantly higher GFR and RPF than Group 2. Additionally, in order to
      demonstrate the change in renal viability among the three groups, the adenosine
      triphosphoric acid level (ATP) and adenylate energy charge ratio (EC) of renal
      parenchymal tissue were measured by high performance liquid chromatography
      (HPLC). Group 2 had lower ATP and EC than Group 1, and Group 3 had higher ATP and
      EC than Group 2. The results of this study suggest that r-ANP is efficacious on
      rat kidney damage induced by CYA and WIT.

PMID- 8139145
TI  - [Renal functional reserve in obstructive nephropathy].
AB  - This study was designed to evaluate renal functional reserve (RFR) in obstructive
      nephropathy using amino acid loading and the effect of angiotensin converting
      enzyme (ACE) inhibitor on RFR. We divided 24 rabbits into 4 groups, consisting of
      a control, 6-hours-bilateral ureteral obstruction (BUO), 24-hour BUO and 24-hour
      BUO pretreated with ACE inhibitor. Following the ligation of the bilateral
      ureters at the vesicoureteral junction, a unilateral ureter was released after a
      6-hour or 24-hour duration in the obstructive groups. We measured RFR and renal
      vascular resistance after releasing a unilateral ureter in BUO. The baseline GFR
      values in the 6-hour and 24-hour BUO groups were significantly lower than that in
      the control. RFR were 0.34 + 0.04 ml/min/kg (control), 0.10 + 0.03 (6-hour BUO),
      0.01 + 0.03 (24-hour BUO) and 0.10 + 0.01 (ACE inhibitor), respectively. RFR in
      the 6-hour BUO group was well preserved compared with that in the 24-hour BUO
      group. Pretreatment with ACE inhibitor in the 24-hour BUO group enhanced RFR to
      the extent of 6-hour BUO. Our results demonstrated that angiotensin II plays an
      important role in decreased GFR with obstructive nephropathy. Moreover, the
      present data suggested that evaluation of RFR might play a key role in the
      recovery of the post-obstructive renal function.

PMID- 8139146
TI  - [Urinary glycosaminoglycans in patients with non-insulin-dependent diabetes
      mellitus, collagen diseases and IgA nephropathy].
AB  - Urinary levels of glycosaminoglycans (U-GAG) were measured in 72 patients with
      non-insulin-dependent diabetes mellitus, 12 patients with collagen diseases, 14
      patients with IgA nephropathy and 35 healthy subjects as controls to investigate
      the clinical significance of urinary GAG. The mean urinary GAG levels in
      diabetics and patients with collagen diseases were 72.4 +/- 36.2 and 147.8 +/-
      59.2 mg/g.cr, respectively. These were significantly higher than the level in
      healthy subjects (46.7 +/- 11.3 mg/g.cr, p < 0.01). The mean urinary GAG level in
      patients with IgA nephropathy was 56.4 +/- 21.0 mg/g.cr and did not differ from
      that in healthy subjects. The mean urinary GAG level in 35 normoalbuminuric
      diabetic patients (U-A1b < 30 mg/g.cr) was 64.4 +/- 25.6 mg/g.cr and was
      significantly higher than that in healthy subjects (p < 0.01). The mean urinary
      GAG levels in 24 microalbuminuric patients (30 < U-A1b < or = 300 mg/g.cr) and 13
      patients with overt albuminuria (U-Alb > or = 300 mg/g.cr) were 71.4 +/- 30.1 and
      95.8 +/- 58.4 mg/g.cr, respectively and were also higher than the level in
      healthy subjects (both p < 0.01). Urinary GAG levels correlated positively with
      urinary albumin levels (r = 0.251, p < 0.05) and urinary N-acetyl-beta-D
      glucosaminidase activities in diabetics (r = 0.491, p < 0.01). The prevalence of
      diabetic macroangiopathies in diabetic patients with elevated levels of urinary
      GAG was significantly higher than that in those with normal levels of urinary GAG
      (p < 0.05).

PMID- 8139147
TI  - [Urinary cross-linked FDP in various renal diseases].
AB  - Fibrin/Fibrinogen degradation products (FDP) and cross-linked FDP (XLFDP) have
      been found in the urine of many patients with renal disease. FDP result from
      fibrinogenolysis and fibrinolysis. It is useful to detect the urinary XLFDP which
      results from fibrinolysis in order to diagnose intraglomerular coagulation. I
      investigated urinary FDP and XLFDP in patients with various renal diseases.
      Urinary FDP and XLFDP were detected by latex aggregation test in the urine of 96
      patients. Urinary XLFDP was measured by enzyme-linked immunosorbent assay (ELISA)
      using monoclonal antibody in the urine of 140 patients. The positive rates of
      urinary XLFDP were higher in chronic renal failure, membranous nephropathy and
      membranous-proliferative glomerulonephritis than in other renal diseases. High
      levels of urinary XLFDP were found in membranous nephropathy, membranous
      proliferative glomerulonephritis and non-IgA nephropathy. There was an obvious
      relationship between urinary XLFDP and the degree of proteinuria, hematuria,
      serum creatinine and intraglomerular fibrin deposits. The high levels of urinary
      XLFDP were detected in the case of severe proteinuria, normal and mild hematuria,
      normal and slightly increased serum creatinine and mild intraglomerular fibrin
      deposits.

PMID- 8139148
TI  - [Nephropathy in patients with primary antiphospholipid antibody syndrome].
AB  - Primary antiphospholipid antibody syndrome (APS) is characterized by abortion,
      thrombosis, thrombocytopenia and/or valvular disease and it is liable to
      complicate systemic lupus erythematosus (SLE). We carried out a study to
      investigate the clinical and renal pathological findings in five patients with
      APS, but not SLE. In the clinical findings, the patients had negative tests for
      proteinuria and hematuria, and their renal function and tubular function were
      within normal limits. In the light microscopic findings, three patients exhibited
      mild mesangial hypercellularity, and two had minor glomerular abnormalities. In
      immunofluorescent study, there were IgM and/or C3 depositions in the mesangial
      area in some cases, and in electron microscopic study, there were no special
      findings other than mesangial hypercellularity. In conclusion, nephropathy is a
      rare complication in patients with APS, unlike systemic lupus erythematosus.

PMID- 8139149
TI  - [Clinical analysis of cases with acute exacerbation of chronic renal failure].
AB  - We analyzed the total number of 42 events of acute exacerbation of chronic renal
      failure (CRF) in 35 patients who were admitted to the Matsuyama Red Cross
      Hospital Kidney Center between 1985 and 1990. These patients consisted of 16
      males and 19 females with a mean age of 59.8 +/- 12.7 years. The most frequent
      original renal diseases were diabetic nephropathy (DM) and arteriosclerotic
      nephrosclerosis (NS). The most frequent acute exacerbation factors were
      dehydration and infection. Four cases died and one case transferred to chronic
      hemodialysis, but the other 37 events (88%) in 31 cases recovered to normal renal
      functioning. Tentative dialysis therapy was performed for 12 events, in which the
      cases with DM as the original disease and infection as the exacerbation factor
      were responsive to this therapy. In the analysis of long-term prognosis, 7 out of
      26 cases died of non-renal diseases, 15 transferred to chronic dialysis therapy
      and only 4 remained in a CRF state. The intervals between the date of discharge
      and that of the start of dialysis therapy was shorter in the cases with DM (mean
      of 5 months) or chronic glomerulonephritis (mean of 7.6 months) than in cases
      with chronic interstitial nephritis, polycystic kidney disease and NS (mean of
      17.7 months). We concluded that even though many of the cases eventually
      transferred to chronic dialysis therapy, appropriate therapy during the acute
      exacerbation period could allow recovery to a natural progressive or
      nonprogressive course in each case.

PMID- 8139150
TI  - [Clinical studies of factors influencing acute tubular necrosis after kidney
      transplantation].
AB  - It is known that the earlier the graft begins functioning after cadaver kidney
      transplantation, the better the graft survival rate and function will be. In
      order to examine the possibility of shortening the period of acute tubular
      necrosis (AIN), we retrospectively studied the effect of several factors on the
      duration of postoperative hemodialysis. The subjects were 27 patients on whom a
      cadaver kidney transplantation was performed during a 6-year period from July 1,
      1986. The mean duration of postoperative hemodialysis was 14.0 days in 26 out of
      the 27 patients. The remaining patient showed a primary non-functioning kidney. A
      significant correlation was observed between the anastomosis time and the
      duration of postoperative hemodialysis. No significant correlations were noted
      between the duration of postoperative hemodialysis and the age of the donor,
      renal function during the 24 hours preceding nephrectomy, or cold ischemic time.
      Moreover, no significant difference was observed in the duration of postoperative
      hemodialysis between patients using a roller pump for perfusion and patients who
      did not. The duration of postoperative hemodialysis was significantly shorter in
      patients using UW solution than in patients using Euro-Collins solution. Graft
      survival rate 6 months and one year after transplantation was 88.9% and 83.3%,
      respectively in the EC group, and 100% and 100%, respectively, in the UW group.
      It was concluded from these results that a short anastomosis time is essential in
      order to shorten the period of ATN after cadaver kidney transplantation, and that
      UW solution is effective in shortening the duration of postoperative hemodialysis
      and improving the graft survival rate thereafter.

PMID- 8139151
TI  - [Maintenance hemodialysis in IgD- lambda -type multiple myeloma associated with
      severe renal failure].
AB  - A 52-year-old man was admitted to our hospital because of oliguric renal failure.
      The patient was well until four weeks earlier, when he developed nausea and
      anorexia. The urea nitrogen was 179 mg/dl, creatinine 29.2 mg/dl, uric acid 19.0
      mg/dl and potassium 8.6 mEq/1. Hemodialysis was started immediately after
      admission. Bone marrow aspiration showed atypical plasma cell infiltration
      consistent with multiple myeloma. The immunoelectrophoresis revealed urinary
      lambda -type Bence Jones protein and serum IgD- lambda -type M protein. The
      findings of renal biopsy study were consistent with myeloma kidney. On the fourth
      hospital day, administration of prednisolone 40 mg and melphalan 2 mg was
      started. The patient also underwent double filtration plasma-pheresis (DFPP).
      Serum IgD level was decreased from 950 to 113 mg/dl. After a course of
      chemotherapy, however, he developed severe leukopenia and was complicated with
      methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This complication
      was successfully treated with imipenem/cilastation and vancomycin combined with
      granulocyte colony stimulating factor (G-CSF). The patient was discharged and
      returned to work on maintenance hemodialysis. Fifteen months after the
      presentation, he manifested progressive peripheral nerve disturbances. Three
      months later, the patient died--not from renal failure, but from ventricular
      arrhythmia. The application of maintenance dialysis therapy to myelomatosis has
      until now been questioned. The present case, however, suggests that aggressive
      treatment consisting of chronic dialysis therapy as well as chemotherapy and
      plasma exchange should be administered even in patients with established renal
      failure.

PMID- 8139152
TI  - [Vasculitic syndromes and renal injury].
AB  - This review emphasizes our increasing understanding of renal involvements in
      vasculitic syndromes. Systemic vasculitis of various size vessels (large, medium,
      and small) can be classified according to the ANCA positivity. Large vessel
      vasculitides are usually ANCA negative and the occurrence of renal vasculitis or
      glomerulonephritis is rare. Inflammatory aneurysm of abdominal aorta exhibits
      peculiar renal injury. In this disease, marked fibrosis of periaorta often
      induces hydronephrosis. On the other hand, ANCA is positive in most of small
      vessel vasculitides. C-ANCA is specific for Wegener's granulomatosis and P-ANCA
      for pauci-immune crescentic glomerulonephritis with or without pulmonary
      hemorrhage. Pathogenetic role of ANCA in renal involvements in small vessel
      angitis can be well explained from the standpoint of ANCA-cytokine sequence
      theory. Another modern topic is lupus vasculopathy. Renal vascular changes in
      lupus nephritis are various in relation to the presence of anti-DNA antibody,
      anti-phospholipid antibody, and anti-endothelial cell antibody, or long
      administration of corticosteroids.

PMID- 8139153
TI  - [Significance of membrane attack complex inhibitory factor expression in cultured
      human glomerular epithelial cells].
AB  - Membrane attack complex (MAC) inhibitory factor (MACIF) is a 20-kD membrane
      protein that inhibits MAC formation on homologous cells. Until recently, a
      functional role of MACIF had been demonstrated in erythrocytes. Therefore, we
      have focused on the fact that glomerular epithelial cells (GECs) are the primary
      target of MAC-mediated damage in rat Heymann's nephritis model of human
      membranous nephropathy. Using immunocytochemistry and western blotting we have
      shown that MACIF is expressed in cultured human GECs. Phosphatidyl-inositol (PI)
      phospholipase C (PLC) reduced MACIF expression in these cells, suggesting that
      MACIF is a PI-linked membrane protein in GECs. In addition, we elucidated that
      MACIF protects GECs against complement-mediated lysis. These findings suggest
      that MACIF expressed on GECs plays an important role in the protection of GECs
      against complement mediated-cellular damage in vivo.

PMID- 8139154
TI  - [Studies on cell-mediated immunity (CMI) in the glomeruli: immunization with GBM
      antigen from Masugi nephritis in Wistar-Kyoto rats].
AB  - The role of cell-mediated immunity in glomerular injury has been extensively
      studied, but the precise mechanism remains obscure. This study was undertaken to
      determine whether the homologous glomerular basement membrane (GBM) combined
      heterogeneous anti-GBM antibody would induce cell-mediated immunity. Wistar-Kyoto
      rats were divided into three groups; group I rats were immunized with homologous
      GBM antigen that was derived from Masugi nephritis and emulsified in complete
      Freund's adjuvant (CFA); group II rats were immunized with homologous GBM antigen
      that was derived from normal rats and emulsified in CFA; group III rats were
      immunized with CFA only. Group I rats demonstrated proteinuria on days 7 and 10
      after immunization. Histologically, mesangial cell proliferation and cell
      infiltration were observed in the glomeruli. No changes in tubulointerstitial
      tissue. CD4-positive cells, CD8-positive cells and macrophages were found in the
      glomeruli, and mononuclear cells were found in the glomerular capillary lumen.
      Group II and Group III rats demonstrated no proteinuria and no histological
      changes. These findings indicated that the altered GBM obtained antigenicity and
      induced cell-mediated immunity in the glomeruli.

PMID- 8139155
TI  - [Analysis of handwriting by the dynamic programming matching].
AB  - We examined the temporal invariance hypothesis in handwriting, using dynamic
      programming (DP) matching algorithm. The DP matching algorithm was originally
      developed for the speech recognition to eliminate fluctuations of time axis
      caused by different speech rates. This algorithm can determine the optimal point
      to-point correspondences (warping function) between the standard velocity pattern
      and different patterns. We found that this algorithm worked well for various
      velocity patterns, even when their total writing time was different from the
      standard pattern. Only 30 to 50 percent of handwriting movements showed temporal
      invariance. The writing movements which didn't show temporal invariance consisted
      of several sub-motor units. The borders between the units were not limited near
      the end of each letter. The results suggest that handwriting of a word does not
      show the temporal invariance and that it is executed by some discrete sub-motor
      units.

PMID- 8139156
TI  - [Estimation of reliability and stability in the data where test-retest intervals
      change over subjects].
AB  - Models for the test-retest situation are proposed, in which an interval between a
      test and a retest changes over subjects. In the model of a single observed
      variable we assume that the true score of the variable changes as a Markovian
      process. We show that stability and reliability of a test can not be estimated
      separately in the ordinary test-retest model which assumes equal stability for
      subjects, but that they can be estimated separately with our model. In the model
      of a latent variable (factor) we assume various stabilities for the latent
      variable and the non-zero covariances of specific factors in a test and a retest.
      These models are applied to actual data, and stabilities and reliabilities of
      tests are estimated quantitatively.

PMID- 8139157
TI  - [Mental development of 'meanings' related to scripts: 'dining' script as an
      example].
AB  - The purpose here is to investigate how the process of relating 'meanings' to
      scripts is influenced by the developmental changes of concepts about these
      activities, with an example of 'dining'. Based on previous studies that the
      concept of 'dining' develops from physiological function orientation to social
      function orientation, second, fourth, and sixth graders, and college students
      were asked to plan 'dining' with a physiological goal or a social one. The
      results are as follows. (1) Generated plans became more connected with goals
      developmentally in both social and physiological context. (2) Second graders who
      attached much importance to physiological function of 'dining' were apt to
      generate plans with physiological meanings even in social goal context.

PMID- 8139158
TI  - [The cognition of intra-familial kinship terms among junior high school
      students].
AB  - A cognitive task concerning intra-familial kinship terms was imposed on 125
      junior high school students (male 57, female 68). Forty-six questions were read
      successively and subjects were required to answer each item. These questions
      consisted of two types; one required the subjects to identify various familial
      relationship (e.g. "my uncle") from everyday description (e.g. "my parent's
      brother"), and the other presented relationship through legal degree of
      relationships (e.g. "my parent's parent's male child, other than my parent"),
      some questions of both types containing redundant information concerning gender.
      The main results were as follows. (1) Correct percentages on lineal relatives
      regardless of question type were very high. (2) High correlation between related
      gender-differentiated kinship terms was observed. (3) While questions employing
      ordinary expressions yielded higher correct percentages than those expressed in
      legal terms, redundant information reduced correct percentages when combined with
      ordinary expression.

PMID- 8139159
TI  - [The influence of the type of conversation on its memory].
AB  - The present study investigated the effect of the type of conversation on the
      recognition memory of statements appeared in the conversation. The experiment
      used two types of conversation; goal-oriented conversation and desultory
      conversation. The examined items were as follows: (1) the recognition memory of
      the surface form of statements which appeared in both types of conversation, (2)
      the effect of whether the sex of speaker was the same as the subject's or not,
      (3) the effect of whether the subject joined the conversation or just listened to
      conversation. Subjects (40 male and female undergraduates) were randomly assigned
      either to the listening condition in which they read the scenario of a
      conversation silently while listening to the tape recorded version of the same
      conversation, or to the utterance condition in which they played the part given
      in the scenario as if they were conversing with a partner whose utterance was
      given by the tape. The following results were obtained. Recognition memory of
      both surface form and content of statements was high in the goal-oriented,
      listening, same-sex condition, in the goal-oriented, utterance, other-sex
      condition, and in the desultory, listening, other-sex condition; it was low in
      desultory, utterance, other-sex condition. These results suggested that the
      recognition memory of conversation was dependent on various factors such as the
      type of conversation, the identity of the speaker (self or non-self), and the
      part played in the conversation (joining or listening).

PMID- 8139160
TI  - [The effect of stimulus motion on visual search].
AB  - One of the unsettled issues in visual search research is whether the search for a
      conjunction of motion and the other physical feature (e.g. color or shape) is
      serial or parallel. In the present experiment, the subjects (six undergraduate
      students) were instructed to search for a target defined by color, shape, motion,
      or combinations of the two out of these three features, and the reaction time was
      measured. The slopes of the regression (number of items in the display vs.
      reaction time) are the largest for a target defined by a conjunction of color and
      shape, the smallest for a target defined by one feature, and intermediate for a
      moving conjunctive target. These results are consistent with those of McLeod and
      colleagues (1988, 1991) which suggest that a specific visual subsystem operates
      as a movement filter.

PMID- 8139161
TI  - Development of haploid and diploid mouse parthenogenones: effect of oocyte aging
      in vivo.
AB  - Mouse oocytes were collected 13.5-29.5 hr after hCG injection at 4 hr intervals,
      then activated with 7% ethanol for 1 min. The oocytes collected 13.5 hr after hCG
      injection did not respond to ethanol activation. High activation rates (90.2
      98.3%) were obtained in oocytes activated 17.5-29.5 hr after injection with hCG.
      Haploid parthenogenones were dominant though the number decreased as the age of
      oocytes advanced (89.5% to 42.0%). The highest number of diploid parthenogenones
      (20.6%) was obtained in oocytes activated 21.5 hr after hCG injection. The number
      of immediate cleavage and morphologically abnormal oocytes increased when the
      oocyte age progressed (0.7% to 34.7% and 1.1% to 23.2%, respectively). The
      percentage of parthenogenones developing to blastocysts decreased with the
      increase in oocytes age: haploid 51.9% to 1.4% and diploid 100.0% to 83.3%. The
      present study demonstrates that the developmental potentials of haploid and
      diploid parthenogenones derived from oocytes at 17.5 and 21.5 hr are higher than
      those derived from oocytes at 25.5 and 29.5 hr after hCG injection.

PMID- 8139162
TI  - Nutritional secondary hyperparathyroidism occurring in a strain of German
      shepherd puppies.
AB  - Five German shepherd puppies, aged between 66 and 174 days (4 of which had the
      same parents) had ananastasia with deformation of limbs. Histopathologically, all
      the puppies showed moderate to marked fibrous osteodystrophy with parathyroid
      gland activation. These puppies were fed a diet consisting of 80% steamed rice
      and 20% raw meat. It was implied that though the diet contained the required
      level of calcium, it contained more than the required level of phosphorus. From
      the results, the present cases were diagnosed as nutritional secondary
      hyperparathyroidism caused by a diet containing too much phosphorus. Based on the
      clinical aspects concerning the development of this condition a familial factor
      was suggested.

PMID- 8139163
TI  - [An evaluation of the role of paired loading tests in selecting the long-term
      drug therapy for patients with stable angina].
AB  - The examination of 208 patients with stable exercise-induced angina has
      demonstrated that the long-term (12 weeks and 12 months) antianginal effect can
      be predicted with a high accuracy from the results of acute pair exercise test
      using the drugs. The negative result of the test with verapamil is not
      informative due to the accumulation of its antianginal effect when the agent is
      used long. The long-term antianginal effect of nitrosorbide is determined not
      only by positive pair exercise test, but mainly by its dosage regimen during a
      day. The fact that half the patients who took labetalol for a long time developed
      tolerance to its anginal effect casts some suspicion on the advisability of its
      administration in stable angina. Lipid peroxidation as a mechanism of platelet
      aggregability regulation.

PMID- 8139164
TI  - [A genetic-epidemiological model of predisposition to ischemic heart disease
      (1)].
AB  - A genetic and epidemiological sample of 20-59-year-old males, Moscow residents (n
      = 3141), was surveyed. The authors obtained data on the prevalence of coronary
      heart disease from epidemiological criteria and genealogical data on
      cardiovascular diseases by the "Familial History" questionnaire in the first
      degree relatives who were interviewed by using a genetic and mathematical
      monolocus diallelic model. It was found that out of the 10 possible variants
      under study a genetic and environmental variant with independent penetrance of 3
      genotypes adequately describes the prevalence of coronary heart disease in the
      families and in the population. This suggest that both genetic and environmental
      factors have an influence on the prevalence of coronary heart disease and that
      there is a possible genetic polymorphism of the disease.

PMID- 8139165
TI  - [The antianginal efficacy of verapamil and nitrosorbide used separately and
      jointly in patients with angina of effort].

PMID- 8139166
TI  - [The effect of pyridinolcarbamate (parmidine) on the microcirculation and
      immunity of patients with stable angina].
AB  - A comparison of the efficacy of treating two patient group (Group 1, patients
      receiving nitrates in combination with parmidin and Group 2, those taking
      nitrates) revealed that the two groups did not differ greatly in the clinical
      effects. In heart failure patients with high capillary permeability, parmidin
      substantially decreased the permeability to protein, which was associated with
      decreases in the baseline high activity of primary lipid peroxidation product in
      plasma red blood cells, which was not observed in the controls. At the same time
      parmidin was demonstrated to exert an unfavourable effect on microhemocirculation
      and to increase the patient's autosensibilisation.

PMID- 8139167
TI  - [Lipid peroxidation as a mechanism for the regulation of platelet aggregation
      activity].
AB  - The paper deals with the role of free radical lipid oxidation in the mechanisms
      of platelet activation. The findings suggest that lipid peroxidation metabolites
      (primary and secondary) are able to produce regulatory effects mediated by
      membrane arrangement on platelet aggregatory properties. At the same time the
      higher levels of conjugated dienes can induce platelet aggregation in unstable
      angina pectoris. This expands the current concepts of the mechanisms of abnormal
      platelet activation and allows it to be classified as a particular system.

PMID- 8139168
TI  - [The risk assessment for a fatal outcome in patients with stable angina based on
      the data from a long-term prospective observation (a comparison of the 5-year
      survival prognosis with the data at the 6th to 12th years of the observation)].
AB  - A rule has been developed to predict coronary death in 377 patients with coronary
      heart disease and stable angina due to coronary stenotic atherosclerosis.
      Gravimetric values of various clinical signs, resting ECG changes, and bicycle
      ergometric testing have been obtained by a computer. A decisive rule has been
      also derived. According to the values of prognostic indices I1 and I2, groups of
      low, moderate, and high risks for fatal outcomes for 5 years have been identified
      and the patient's survival during a subsequent follow-up of 6 to 12 years has
      been assessed. The developed scheme of prognosis permits its use in practice.

PMID- 8139169
TI  - [The characteristics of the hormonal and vascular reactions to short-term salt
      loading in patients with borderline arterial hypertension depending on the level
      of psychoemotional tension].

PMID- 8139170
TI  - [Biochemical and electrocardiographic methods in the intravital assessment of
      metabolic disorders in the heart muscle of myocardial infarct patients].
AB  - Two methods--electrocardiographic (recording ECG cartograms in 35 leads) and
      biochemical--for assessing myocardial necrotic formation in the convalescents and
      death victims of myocardial infarction, were compared. The author considered
      changes in the number of complexes with ST segment elevation and Q wave square
      (QS) out of ECG parameters. There were uniform changes both in
      electrocardiographic parameters, and in the peripheral blood activity of creatine
      phosphokinase MB, an isoenzyme specific to the myocardium. There were significant
      differences between the changes in the death victim group as compared to the
      convalescents. It is shown that myocardial infarction is a process which is
      extended in space and time rather than momentary.

PMID- 8139171
TI  - [A biochemical study of creatine phosphokinase in the myocardium and its
      morphological changes in patients with acute vascular surgical pathology].
AB  - The structure and metabolism of various myocardial portions, including the
      activity of creatine phosphokinase (CPK), were studied by using the autopsies of
      patients who had died in a surgical clinic. The biochemical studies demonstrated
      a decrease in CPK activity, which was pronounced in patients with atherosclerotic
      aneurysm and abdominal aortic rupture. The morphological studies revealed
      individual cardiomyocytic lesions, segmental lesions of papillary muscle. There
      was reduced activity of redox enzymes in the fragmentation areas of muscle
      fibers. Various surgical abnormality of vessels was accompanied by progressive
      myocardial hypoxia and drastically decreased activity of CPK and the tested
      hydroxyreductases.

PMID- 8139172
TI  - [The clinico-electrocardiographic prodromes of fatal cardiac arrhythmias in
      patients with an acute myocardial infarct].
AB  - The authors made a retrospective analysis of case histories of 201 patients who
      had died of fatal cardiac arrhythmias. The predictors of their death were
      ventricular fibrillation in 133 (66.2%) patients, asystole in 68 (32.8%),
      electromechanical dissociation in 2 (1%). Terminal sinus tachycardia, atrial
      fibrillation and flutter, the second-third degree atrioventricular block, the
      third-fifth grade ventricular extrasystole were the most common clinical and
      electrocardiographic prodromes of ventricular fibrillation. In the development of
      the latter, various mixed disturbances of cardiac rhythm and conduction in
      combination with prolonged Q-T interval were of more unfavorable value. Asystole
      was more frequently preceded by the second-third degree atrioventricular block,
      complete bundle branch block, third-fifth grade ventricular extrasystole, atrial
      fibrillation and flutter, and various mixed disturbances of cardiac rhythm and
      conduction. Cardiac arrhythmias and conduction disturbance with prolonged Q-T
      interval were found to be precursors of asystole in 84.8%.

PMID- 8139173
TI  - [The effect of the long-term use of a diet enriched with omega-3 polyunsaturated
      fatty acids on the fatty acid composition, fibrinolytic system indices and lipid
      spectrum of the blood in patients with ischemic heart disease].
AB  - Fatty fish was included for 7 months into diet of 11 male patients with early
      stages of ischemic heart disease. Effects of this diet modification on serum
      fatty acids, lipids and some variables of hemostasis were studied. After control
      period, patients ate 120-160 g/day of canned Pacific sardine (about 5 g omega-3
      polyunsaturated fatty acids) per day. Two patients refused to participate after 2
      months and 1 was lost for follow-up. After 7 months of diet, the proportion of
      eicosapentaenoic acid (EPA) in blood lipids increased from 0.67 + 0.26 to 4.7 +
      1.5% (p < 0.015) and of docosahexaenoic acid (DHA) from 2.3 + 1.1 to 4.3 + 1.1%
      (p < 0.015). Ratio of EPA to arachidonic acid (AA) rose from 0.1 + 0.02 to 0.9 +
      0.4 (p < 0.015). Mean serum triglyceride concentration fell after first month
      from 179.5 + 79.0 to 99.1 + 30.0 mg/dl (p < 0.015) and remained at this level
      throughout the study. No significant changes were observed in serum total and
      high-density lipoprotein cholesterol. Plasma activities of tissue-type
      plasminogen activator inhibitor, contents of plasminogen, alpha 2-antiplasmin,
      antithrombin III and protein C also did not change. Plasma fibrinogen moderately
      decreased. Its decrease became statistically significant at month 5 (from 3.8 +
      0.5 to 3.0 + 0.7, p = 0.021). Thus, the regimen used in this study led to a
      substantial and steady increase in plasma EPA, DHA and EPA/AA ratio. This was
      accompanied by sustained decrease in plasma triglycerides. There were no
      profibrinolytic changes in the parameters studied.

PMID- 8139174
TI  - [The choice of the optimal regimen for apheresis of the low-density lipoproteins
      in patients with familial hypercholesterolemia by using mathematical modelling].
AB  - The study was undertaken to enhance the effectiveness of a low-density
      lipoprotein apheresis procedure by using the mathematical approach to choosing an
      individual sorption regimen for each patient when the cholesterol concentration
      given by a physician was achieved in the shortest time. The experimental
      estimation of time course of changes in plasma cholesterol levels at the column
      inlet and outlet during low-density lipoprotein apheresis allowed the optimal
      parameters of the procedure to be calculated. The adequacy of the proposed
      methods to the real data was examined by the paired t-test (p < 0.0001). The
      optimal regimen was chosen for 5 patients with familial hypercholesterolemia. It
      is shown that the optimization of the regime will reduce the time of the
      procedure to 47 min, by removing the same amount of a substance.

PMID- 8139175
TI  - [The use of Enduracin--a prolonged-action form of nicotinic acid--in correcting
      atherogenic dyslipidemias].
AB  - The hypolipidemic effects of induracin, a new long-acting nicotinic acid dosage
      form based on the waxy matrix, and its tolerance were studied in 31 patients with
      Types IIa and IIb hyperlipoproteinemias in a 6-month blind crossover study. There
      were decreases in the levels of total cholesterol by 9-13% and low density
      lipoprotein cholesterol by 12-22%, an increase in high density lipoprotein
      cholesterol by 12-15%, and a good dynamics in the ratio of blood lipid-transport
      proteins--a 12-16% increase to the levels of apoprotein AI to a 29% decrease in
      those of apoprotein B. The drug is well tolerated by patients and may be
      recommended for correction of atherogenic dyslipidemias.

PMID- 8139176
TI  - [The thrombocyte function of subjects with atherogenic hyperlipidemias during
      lovastatin treatment].
AB  - The effects of lovastatin on in vivo spontaneous and in vitro ADP-induced
      platelet aggregability were studied in the blood of 36 persons with primary
      hyperlipidemias (HLP) of Types IIIa and IIb. In addition to decreases in blood
      cholesterol levels by an average of 33% and the atherogenicity coefficient to the
      normal levels, there was an increase in spontaneous and/or ADP-induced platelet
      aggregability in the first 2-3 months of lovastatin therapy. Lovastatin-induced
      in anti- and proaggregatory potential in the platelet-vascular wall system
      towards of the latter and spontaneous intravascular platelet formation suggest
      that there is a higher risk for thromboembolic events in the examined patients
      with Type II HLP, especially if they have coronary heart disease, during early
      stages of the drug administration. Therefore, there are reasons for recommending
      that lovastatin should be given under the control of the platelet hemostatic
      system.

PMID- 8139177
TI  - [Functional study of the heart valve apparatus by 2-dimensional Doppler
      echocardiography in rats with experimental endocarditis caused by Coxsackie B3
      viruses].
AB  - Eleven neonatal cotton rats were infected with Coxsackie B3 viruses, 9 animals
      served as controls. The course of the disease was followed for 44 to 154 days.
      Electro- and phonocardiography, two-dimensional Doppler echocardiography,
      morphological and histological studies were performed in the experiment. All the
      histologically examined infected rats were found to develop myocarditis, whereas
      75% of the animals had valvulitis. The total number of the afflicted values was
      10, out of them the mitral, tricuspid, and pulmonary trunk valves accounted for
      40, 40, and 20%, respectively. Doppler echocardiography revealed organic mitral
      and tricuspid insufficiencies in the outcome of valvulitis induced by Coxsackie
      B3 viruses due to the impairment of valvular cusp.

PMID- 8139178
TI  - [Modifications to the solution for reperfusion of the ischemic heart].
AB  - Isolated working guinea pig hearts were subjected to 30-min total normothermic
      ischemia and 30-min reperfusion with modified Krebs solution to which various
      agents were added. The presence of glutamate in the solution resulted in better
      recovery of cardiac pump function and higher myocardial energy phosphate levels.
      Addition of phrelone, a calmodulin inhibitor, or adenosine and ribose did not
      improve pump function. The similar functional recovery was observed after
      addition of taurine instead of glutamate and their combination exerted even
      higher functional recovery while further addition of phosphocreatine was not so
      effective.

PMID- 8139179
TI  - [Precordial mapping with the use of the PK-35M multielectrode belt].

PMID- 8139180
TI  - [The prognostic significance of bicycle ergometry data in patients with unstable
      angina].
AB  - A total of 179 patients with unstable angina were studied. There were no
      complications after bicycle ergonomic tests performed after the patient's
      condition improvement. An analysis of bicycle ergonometric data and long-term
      outcomes in 169 patients revealed that the outcome was significantly worse in
      case of positive test (p = 0.007). The validity of this assessment was confirmed
      over 49 months. The criterion of test cessation was the most predictor in the
      assessment of a long-term outcome. In pain development accompanied by ECG
      changes, only 20% of patients had an uncomplicated course 48 months later. Deaths
      were more frequently observed in the late period if there was 2 mm or more ST
      segment depression on exercise testing (p = 0.001).

PMID- 8139181
TI  - [Comparative evaluation of the methods for treatment of compressive thoracic
      outlet syndrome].
AB  - The co-operative investigation of two clinics on the basis of examination and
      treatment of 78 patients with the thoracic outlet syndrome for 5 years is
      presented. The comparative assessment of the two main methods for surgical
      treatment--1st rib resection and resection of the anterior scalene muscle has
      been performed. The results of less traumatic operation of the anterior scalene
      muscle resection employed in certain forms of the disease are similar to those in
      performance of more radical operation, the incidence of complications is lower.

PMID- 8139182
TI  - [Pharmacologic protection of brain in surgery of the brachiocephalic arteries].
AB  - On the basis of experimental and clinical data, the subclinical ischemic brain
      damage resulting from temporary clamping of the carotid artery during performance
      of the reconstructive operation has been established. The changes were revealed
      in sufficient, according to the existing criteria, collateral circulation. Before
      placing the clamp onto the carotid artery as a preventive method for
      intraoperative medicamental brain protection, intraarterial administration of
      piracetam, which possesses anti-ischemic, membrane stabilizing and antioxidant
      properties, has been suggested.

PMID- 8139183
TI  - [Chronic coronary insufficiency in the genesis of atherosclerotic circulation
      encephalopathy].
AB  - The interconnection between coronary insufficiency and cerebral discirculation in
      the genesis of discirculatory encephalopathy has been established. Almost in
      every fifth patient with discirculatory encephalopathy, or ischemic heart
      disease, combined damage to the coronary arteries and brachiocephalic trunk was
      diagnosed.

PMID- 8139184
TI  - [Emergency angioplasty of the coronary arteries in the treatment of acute
      myocardial infarction].
AB  - The comparative assessment of lethality, incidence of development of repeated
      myocardial infarction and complications, indices which evidence in favour of
      improvement of the left ventricular function in 36 patients with acute myocardial
      infarction (group 1) who underwent superselective intracoronary thrombolysis
      alone, and in 10 patients (group 2) who underwent emergency coronary angioplasty
      after successful intracoronary thrombolysis is presented. The best immediate and
      long-term results were noted in group 2 patients.

PMID- 8139185
TI  - [Use of spirometry in the evaluation of the cardiovascular and respiratory system
      in mitral valve prosthesis].
AB  - Before the operation, in 103 patients with the defects of the right and left
      atrioventricular valves, echocardiography and spiro-ergometry were performed.
      Their performance permitted to reveal latent myocardial incompetence in these
      patients. Changes in the indices of external respiration and gas exchange at a
      level of the threshold standard load can serve as objective criteria for
      assessment of reserve resources of the cardiovascular and respiratory systems and
      prognosis of the development of acute cardiac failure at the shortest period
      after the mitral valve replacement.

PMID- 8139186
TI  - [Surgical treatment of multiple occlusions of the aortic arch arteries].
AB  - The results of treatment of 174 patients with lesions of the arteries of the
      aortic arch are presented. Multiple lesions of the coronary arteries were
      revealed in 78 patients, of the brachiocephalic trunk--in 45, their combination-
      in 52. In patients with the ischemic heart disease, in average, 3,4 aortocoronary
      shunts were placed. In patients with the impaired cerebral circulation,
      reconstruction of 2-3 arteries was performed simultaneously in their unilateral
      lesions. In case of their bilateral lesions, the blood flow restoration was
      performed in two stages with a 2-4 week interval. Improvement of the indices of
      intravascular hemodynamics was achieved in 97.5% of the patients, neurologic
      symptoms were completely eliminated in 71% of the patients. Three patients died
      from cardio-vascular failure.

PMID- 8139187
TI  - [Method of surgical treatment of mitral valve stenosis depending on the extent of
      its calcinosis].
AB  - On the basis of studying the immediate and long-term results of treatment of 329
      patients with calcinated mitral stenosis, the progressive aggravation of the
      immediate outcome of the operation in II and III-IV degree of mitral valve
      calcinosis is demonstrated. The data have been confirmed by actuarial analysis of
      the patients' survival and stability of a good result. The authors consider it
      expedient to perform mitral commissurotomy only in patients without valvular
      calcinosis and I degree calcinosis. In more severe affection, mitral valve
      replacement is indicated.

PMID- 8139188
TI  - [Medial approach to the proximal section of the vertebral artery].
AB  - An access to the initial portion of the vertebral artery which is distinguished
      by medial relative to the internal jugular vein approach to the subclavian
      vertebral arterial segment is described. In its use in 34 patients, no
      complications which occur in conventional access with the lateral relative to the
      internal jugular vein approach (diaphragmatic nerve paresis, plexitis, injury to
      the thoracic duct) were noted.

PMID- 8139189
TI  - [Use of magnetic therapy combined with galvanization and tissue electrophoresis
      in the treatment of trophic ulcers].
AB  - The results of treatment of 86 patients with the use of magnetotherapy in
      combination with galvanization and intratissue electrophoresis are presented. To
      create an electric field, the "Potok-1" apparatus with a density of current equal
      to 0.05-0.1 mA/cm2 was employed. Simultaneously, the "MAG-30" apparatus for low
      frequency magnetotherapy with induction of 30 mT and area of exposure of 20 cm2
      was applied to a trophic ulcer site. The use of magnetogalvanotherapy in the
      complex of treatment of trophic ulcers of the lower extremities is recommended.

PMID- 8139190
TI  - [Prevention of suppurative inflammatory complications in traumatology].
AB  - On the basis of the data of clinical, bacteriologic, immunologic investigations,
      the system for prevention of purulent-inflammatory complications (PIC) in
      treatment of closed and open fractures of the extremities has been developed. Use
      in the clinic of a system for prophylaxis permitted to reduce the incidence of
      PIC development in operative treatment of closed fractures from 5.6 to 1.64%,
      after performance of the emergency operations for open injuries--from 18.3 to
      5.4%.

PMID- 8139191
TI  - [Use of transfusion of cryopreserved allogenic bone marrow for the treatment of
      suppurative septic complications of acute appendicitis].
AB  - In diagnostic study of the immunocompetent system in 36 patients with purulent
      septic complications of acute appendicitis, the immunodeficient state has been
      revealed. Inclusion into the complex of treatment of transfusion of the
      cryoconservated bone marrow from a cadaver contributed to accelerated
      normalization of the immunocompetent system, shortening of the time of wound
      cleaning from necrotized tissues and its healing, duration of the period of
      rehabilitation of the patients.

PMID- 8139192
TI  - [Comparative characteristics of thyroid cancer morbidity based on clinical data].
AB  - Comparative assessment of the incidence of thyroid cancer in patients operated on
      for different thyroid diseases from 1980 to 1986 (2448 cases, group 1), and from
      1987 to 1991 (1993 cases, group 2) was carried out. The increase in incidence of
      thyroid cancer in group 2 patients was noted as well, as that in incidence of
      cancer development among the other hyperplastic diseases of the thyroid gland,
      autoimmune thyroiditis in particular. The results obtained are indicative of the
      necessity for correction of the tactics of treatment and prophylactic follow-up
      of the patients with different forms of goiter.

PMID- 8139193
TI  - [Diagnosis and surgical treatment of traumatic intracranial membrane hematoma of
      rare localization].
AB  - The results of treatment of 93 patients with traumatic membrane hematoma of rare
      location (membrane hematoma of the posterior cranial fossa, epidural hematoma of
      the anterior cranial fossa, occipital pole, hematoma located over the upper
      longitudinal sinus, intercerebral subdural hematoma, subdural hematoma of basal
      location) have been analysed. Difficulties in diagnosis of hematoma are
      conditioned by a variety of clinical signs. The informative value of the
      different methods of diagnosis were assessed, peculiarities of surgical
      intervention noted.

PMID- 8139194
TI  - [Emergency in children with implanted cerebrospinal fluid shunt].
AB  - In 455 pediatric patients with progressive hydrocephaly of non-tumour genesis, a
      valve liquoro-shunting system was implanted. At different periods after the
      operation (up to 5 years), 4.8% of the patients developed the purulent-infective
      complications, dysfunction of a system occurred--in 20.4%. The causes, clinical
      signs of the emergency state are analysed, the recommendations on carrying out
      the therapeutic measures are given.

PMID- 8139195
TI  - [Microsurgical anatomy of meningioma of the posterior cranial fossa].
AB  - On the material of 107 intraoperative and 19 section specimens, a topographic
      anatomy of meningiomas of the posterior cranial fossa was studied. The groups of
      tumours were distinguished, depending on location of primary meningioma and
      direction of its growth. Tumour interrelations with the caudal cranial nerves and
      surrounding vessels were studied.

PMID- 8139196
TI  - [Reconstructive surgery of abdominal aortic aneurysm].
AB  - The authors have developed the methods for performance of a reconstructive
      operation for abdominal aortic aneurysms which permit to avoid prolonged clamping
      of the abdominal aorta. On the basis of the results obtained, a conclusion of the
      high effectiveness of these methods has been drawn.

PMID- 8139197
TI  - [Use of ventriculojugulostomy and lumbosaphenostomy for the treatment of
      hydrocephalus of various etiology].
AB  - Analysed were the results of treatment of 85 patients with hydrocephaly of
      different genesis: 12 (14.1%) patients--occlusive, 73 (85.9%)--communicating
      hydrocephaly, including 31 (36.4%)--with normal cerebrospinal fluid pressure.
      Ventriculojugulostomy was performed in 55 patients, lumbosaphenostomy--in 30.
      Stabilization of hydrocephaly was achieved in 89.4% of the patients at the near
      postoperative period, in 81.5%--at the period of up to 17 years after the
      operation. Shunt revision was performed in 19 (22.3%) patients.

PMID- 8139198
TI  - [Treatment of patients with multiple traumatic injuries to the peripheric
      nerves].
AB  - Examined were 106 sufferers with multiple injuries to the peripheral nerves of
      the extremities. The expediency to use the different methods of surgical
      intervention, depending on the level and nature of injury have been
      substantiated. An adequate tactics for surgical treatment of the sufferers with
      regard for the level and severity degree of an injury to the extremity has been
      developed. The immediate and long-term results of treatment of the patients were
      studied.

PMID- 8139199
TI  - [Syndrome of "Pseudo acute abdomen" in minor craniocerebral injury].
AB  - In 112 sufferers with light craniocerebral trauma, laparocentesis, or
      microlaparotomy was performed for "pseudoacute abdomen". The main causes of the
      development of the syndrome were distinguished: fracture or contusion of the
      bones, contusion of the abdominal wall and organs of the abdominal cavity,
      exacerbation of chronic disease of the abdominal cavity, injury to the organs
      adjacent to the diaphragm.

PMID- 8139200
TI  - [Methodologic approaches to conducting clinical trials for antibacterial
      preparations in surgery].

PMID- 8139201
TI  - [Long-term asymptomatic abscess arising as a result of injections of
      corticosteroid hormones in a child with Addison's disease].

PMID- 8139202
TI  - [Recurrent intestinal invagination in an 8-month-old child].

PMID- 8139203
TI  - [Rare complication after appendectomy in a child].

PMID- 8139204
TI  - [A method of intestinal decompression].

PMID- 8139205
TI  - [Diagnosis of primary gallbladder cancer].

PMID- 8139206
TI  - [A case of liver abscess perforating into the abdominal cavity].

PMID- 8139207
TI  - [Emergency reoperations in the reconstructive surgery of abdominal aorta and
      major arteries of the lower extremities].
AB  - The experience with treatment of 564 patients who underwent 642 reoperations on
      the arterial vessels, including 281 emergency operation, are presented. The
      causes of the development of pronounced ischemia of the lower extremities and
      that of the extreme situation are considered. The surgical tactics for the
      treatment in cases of transplant infection, erosive bleeding from aortal
      anastomosis etc. have been developed. The original methods for surgical
      correction in performance of a reoperation have been suggested, the analysis of
      the results of treatment has been performed.

PMID- 8139208
TI  - Para-aortic lymph node dissection for the treatment of advanced gastric cancer.
AB  - Para-aortic lymph node (No. 16) metastasis has been accepted as a factor
      responsible for non-curability in gastric cancer surgery. Recently in Japan,
      after detailed experimental and clinical studies of the lymph flows from the
      stomach and/or perigastric nodes to these No. 16 nodes, it is now considered to
      be curable. From 5 autopsy cases, the mean number of No. 16 nodes has been
      determined to be 43. The frequency of positive No. 16 metastasis (No. 16(+)) was
      found to be 24%, occurring in 35 of 144 cases with advanced gastric cancer
      following R3 gastrectomy plus No. 16 dissection. The 5 year-survival rate of R3+
      No. 16 dissection was 70.1% in n1(+), 49.8% in n2(+) and 24.3% in n3(+) and had
      better prognoses (by Kaplan-Meier statistics) than those without dissection of
      the No. 16 nodes. Only 37 patients in the Japanese literature have had No. 16
      dissections, and were confirmed histologically to have had No. 16(+) and
      subsequently survived more than 5 years. The number of those surviving No. 16(+)
      can be expected to increase in the near future with the adoption of R3
      gastrectomy plus No. 16 dissection.

PMID- 8139209
TI  - Effects of aortic and pulmonary balloon valvuloplasty on systolic and diastolic
      cardiac function in children--echocardiographic evaluation.
AB  - Echocardiography (ECHO) was used to assess the systolic and diastolic cardiac
      function before and after balloon valvuloplasty (BV) in children with congenital
      valvular aortic stenosis (AS) or congenital valvular pulmonary stenosis (PS), as
      compared to age-matched control subjects. BV was performed on each of 7 patients
      with AS and 9 patients (one patient twice) with PS. BV was effective in all
      patients. In the AS group the left ventricular outflow pressure gradient was
      significantly decreased from 67 +/- 16 to 29 +/- 15 mmHg (p < 0.01), and in the
      PS group the right ventricular outflow pressure gradient was significantly
      decreased from 64 +/- 21 to 31 +/- 16 mmHg (p < 0.01). To evaluate the systolic
      function, M-mode ECHO was employed. Before BV, both the AS and PS groups had a
      higher ejection fraction (EF) and smaller left ventricular (LV) dimension than
      the control group. Also, before BV, the AS group had severe LV hypertrophy, and
      the PS group had thick right ventricular wall (RVW) and thick intraventricular
      septum (IVS). These abnormalities were not significantly changed immediately
      after BV or in the short term after BV, though they became normalized later, in
      the intermediate term after BV. To evaluate the diastolic function, the
      ventricular inflow pattern was assessed using pulsed Doppler ECHO. Before BV,
      despite the LV hypertrophy in the AS group, the LV inflow indices were similar to
      those of the control group. During the follow-up period after BV, the LV inflow
      indices of the AS group did not change. On the other hand, before BV, both the RV
      and LV inflows of patients with PS had abnormal diastolic filling patterns with
      decreased filling volumes during early diastole and increased filling volumes
      during atrial contraction. Immediately after and in the short term after BV,
      there were no significant changes in the diastolic indices of the patients with
      PS, but later the abnormal indices became normal with an improvement in the RVW
      and IVS hypertrophy. These data indicate that the LV hypertrophy may be related
      to the small LV and the high EF in the AS group before BV. Also, the RVW
      hypertrophy, the IVS hypertrophy, and the RV high pressure load to the LV through
      the IVS may be related to the small LV, high EF, and abnormal two chamber inflow
      in the PS group before BV. This small LV could maintain the cardiac output by
      elevating EF.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8139210
TI  - Clinicopathological characteristics of colorectal submucosal carcinoma with lymph
      node metastasis.
AB  - The clinicopathological characteristics of colorectal submucosal carcinoma with
      lymph node metastasis are described. Lymph node positive metastasis was found in
      10 (11%) of 87 cases. The depth of submucosal invasion was classified as sm1, sm2
      or sm3. Lymph node positive metastases were found in 18% of the cases at sm2 or
      more, in 31% of those without adenomatous components, in 39% of those with
      positive lymphatic permeation, in 41% of those with positive budding, and in 56%
      of all the moderately differentiated adenocarcinomas. These characteristics are
      risk factors and are important for the prediction of lymph node metastasis from
      colorectal submucosal carcinoma. Bowel resection with lymphadenectomy is
      indicated in the presence of any one or more risk factors.

PMID- 8139211
TI  - Cell cycle analyses of extramammary Paget's disease.
AB  - The cell cycle of Paget cells in extramammary Paget's disease was investigated
      using microscopic analysis of the DNA content, and using immunohistochemistry for
      5-bromodeoxyuridine (BrdU) incorporation. Stripped skin was treated with
      tetrasodium ethylendiamine tetraacetate dihydrate (EDTA) and trypsin, and
      epidermal cells suspensions were obtained. Microscopic analysis of the DNA
      content in the cells was performed. The resulting DNA histogram was close to the
      normal ploidy. Specimens from the involved skin were incubated with BrdU, and
      sections were immunostained with anti-BrdU monoclonal antibody. A few nuclei
      showed positive staining for BrdU. The present study showed that the
      proliferative potential of Paget cells in extramammary Paget's disease was low.
      This may explain why lesions of extramammary Paget's disease enlarge rather
      slowly.

PMID- 8139212
TI  - Therapeutic rectoscopy for rectal tumors.
AB  - A surgical resection in the middle or upper region of the rectum is often
      technically difficult because of the anatomical inaccessibility of the site. A
      new rectoscopic operative technique reported by Buess et al. (1985, 1987, 1988)
      and Kipfmuller et al. (1988) permits microsurgery in the rectum and is less
      aggressive than other procedures. This technique was used in 7 patients with
      rectal tumors using an articulated monocular-optical system. The postoperative
      course in all patients was free from any complications and the patients were
      discharged at the latest on the eighth day after the operation. A stereoscopic
      optical system, a new surgical rectoscope, other special surgical instruments, as
      well as a modification to an insufflation device are necessary for improving the
      endoscopic operation.

PMID- 8139213
TI  - Neutrophilia and high level of interleukin 8 in the bronchoalveolar lavage fluid
      of diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis (DPB) is a chronic airway disorder exclusively seen in
      Japan, characterized by chronic inflammation of the respiratory bronchioles
      leading to air flow obstruction. Although the pathogenesis of the disorder is
      unknown, current studies based on bronchoalveolar lavage (BAL) have implied an
      important role of neutrophil-mediated inflammation as a characteristic
      pathological feature of the disease. Interleukin 8 (IL-8), a cytokine with potent
      chemotactic activity for neutrophils, has been proven to have close association
      with many inflammatory disorders. In this study, neutrophil chemotactic activity
      (NCA) and IL-8 were measured in the BAL fluid in eight patients with DPB to
      examine the roles of IL-8 in the neutrophil recruitment to the lower respiratory
      tract in DPB. Significantly higher levels of NCA and IL-8 were demonstrated in
      the BAL fluid of DPB patients (71.6 +/- 3.6%, 491.9 +/- 48.0 pg/ml, respectively)
      compared with that of chronic bronchitis (CB) patients (24.8 +/- 2.8%, 54.1 +/-
      13.9 pg/ml, p < 0.001) and of healthy control subjects (7.0 +/- 0.9%, 14.2 +/-
      3.9 pg/ml, p < 0.001). The IL-8 values were positively correlated with the NCA in
      the BAL fluid of DPB patients. Treatment with anti-IL-8 could significantly
      inhibited the NCA. These results suggest that IL-8 plays an important role in the
      recruitment of neutrophils to the lower respiratory tract in DPB.

PMID- 8139214
TI  - Prevalence in Sweden of human papillomavirus type 16 infection in CIN II-III
      cases assessed by a PCR method.
AB  - The presence of human papillomavirus (HPV) 16 in cervical intraepithelial
      neoplasia (CIN)II-III cases was studied by means of a polymerase chain reaction
      (PCR)-based method applied to paraffin-embedded tissues. Twenty-two of 45 (49%)
      cases showed a positive signal determined by direct visualization on gel stained
      with ethidium bromide. Fourteen of these cases were confirmed by dot blot
      hybridization, which accords with a prevalence of HPV 16 infection in 31% of
      Stockholm patients with CIN II-III. The latter value is lower than that published
      elsewhere (Young et al. 1989; Maki et al. 1991; Skydberg et al. 1991).

PMID- 8139215
TI  - Immature teratoma of the uterine fundus.
AB  - An exceedingly rare case of extragonadal immature teratoma, which occurred
      primarily in the uterus, is described. The tumor developed into the pelvic cavity
      from the uterine fundus and consisted of ectodermal, mesodermal and endodermal
      derivatives. There were also significant amounts of immature elements; immature
      neuroepithelium with brisk mitotic activity, immature mesenchymal tissue,
      immature cartilage, immature striated muscle and immature hepatic tissue.
      Histologically, it was classified as a grade 3 immature teratoma. Treatment
      consisted of total simple hysterectomy followed by 2 courses of combination
      chemotherapy with vincristine, actinomycin D and cyclophosphamide (VAC). The
      patient was well and without evidence of recurrence at 5 years post-operatively.

PMID- 8139216
TI  - Evidence for beta-adrenoceptors in rat proximal convoluted tubules.
AB  - It is well documented that renal catecholamines, acting as paracrine or autocrine
      substances, modulate reabsorption of sodium and other substances in renal
      tubules. However, beta-receptors or the resulting stimulation of adenylate
      cyclase (AC) have not been measured directly in the proximal convoluted tubules
      (PCT) of mammalian kidney. In this study, the beta adrenergic receptors in the
      PCT from rat kidney were characterized pharmacologically by measuring agonist
      stimulated adenylate cyclase activity. Isoproterenol (ISO) (10 microM)
      significantly increased AC activity in the microdissected PCT (ISO, 193.0 +/-
      23.6 vs basal, 118.7 +/- 14.3 fmol/mm/20; n = 8, p = 0.004). The stimulation of
      AC in PCT by ISO was blocked by 10 microM propranolol (p < 0.01); it was also
      blocked by either the beta-1-adrenergic blocker, 10 microM atenolol (p < 0.05),
      or the beta-2-adrenergic blocker, 10 microM ICI-118551 (p < 0.05). The beta
      adrenergic receptor binding sites were localized by autoradiography; specific
      [125I] iodocyanopindolol ([125I] ICYP) binding could be measured in the
      microdissected rat PCT. In conclusion, these findings provide evidence for beta
      adrenergic receptors in the PCT in rat kidney by radioligand binding and beta
      adrenergic agonist stimulated AC activity.

PMID- 8139217
TI  - Mast cells and histamine release in Crohn's disease.
AB  - To study the role of intestinal mast cells in Crohn's disease, a sensitive glass
      fiber histamine assay was conducted in conjunction with mechanical dispersion of
      surgical specimens of 80 macroscopically actively inflamed colons, 40 non
      inflamed colons, 40 actively inflamed ileums, and 16 non-inflamed ileums from
      patients with Crohn's disease and 96 control subjects. A strong correlation was
      found between the number of mast cells and the total histamine content in the
      controls (r = 0.682) (p < 0.05). The number of mast cells was decreased in
      Crohn's disease as compared with the controls (p < 0.01). Intestinal mast cells
      release histamine in a dose-dependent manner after challenges with anti-IgE
      (1.875-240.0 U/ml). A significant difference was noted in the release by anti-IgE
      between actively inflamed and non-inflamed colons of patients with Crohn's
      disease or control subjects (p < 0.01). Mast cells in actively inflamed tissue
      with Crohn's disease were shown to have different roles in the pathogenesis of
      inflammation.

PMID- 8139218
TI  - [Unemployment is bad for social health. Half a job for everyone].

PMID- 8139219
TI  - [A plea for spirituality in care. The hidden gold in a seemingly useless life].

PMID- 8139221
TI  - [Meeting "Ecology in the Hospital". Where did the shock go?].

PMID- 8139220
TI  - [ How decubitus ulcers can be prevented].

PMID- 8139222
TI  - [Pro-mente-sana meeting: communication in the hospital. Psychiatric patients:
      experts in their own disease"].

PMID- 8139223
TI  - [A nursing story].

PMID- 8139224
TI  - [The crisis of human systems. A painful chance].

PMID- 8139225
TI  - [Semantics, rationality and subjectivity. The problem of pleasure].

PMID- 8139227
TI  - [The economically enforced change of job].

PMID- 8139226
TI  - [The newborn with spina bifida. Mourning for the imaginary child].

PMID- 8139228
TI  - [The fifth function of nursing care according to the new regulations.
      Implications for education and practice].

PMID- 8139229
TI  - [Don't grow callous in these rough times].

PMID- 8139230
TI  - [The perverted image of mental disease].

PMID- 8139232
TI  - [A partnership without power struggle].

PMID- 8139231
TI  - [Psychiatric patients: specialists in their own disease].

PMID- 8139233
TI  - [The case of the Mexican seasonal workers in the U.S.A.. How to integrate popular
      beliefs].

PMID- 8139234
TI  - [When death is the price of engagement. Against silence and oblivion].

PMID- 8139235
TI  - [Noise and health. Let us not turn deaf].

PMID- 8139236
TI  - [If only I could say it].

PMID- 8139237
TI  - [Subtle violence--expression of hidden aggression].

PMID- 8139238
TI  - [Practical experiences with automatic data processing].

PMID- 8139239
TI  - [Personnel law on paper--law of the jungle in reality].

PMID- 8139240
TI  - [Inquiry by the Swiss Nursing Association, Berne section, among older nurses.
      Physical complaints--insufficient precautions].

PMID- 8139241
TI  - [The collective health insurance of the Swiss Nursing Association: they still
      save on premiums].

PMID- 8139242
TI  - [Encouragement to save. The canton Ticino as an example].

PMID- 8139243
TI  - [Working with aphasic patients. Understanding the silence].

PMID- 8139244
TI  - [Inquiry. Permanent education in Switzerland: first results].

PMID- 8139245
TI  - [Models of man and care. 1. Attempts at explaining human personality].

PMID- 8139246
TI  - [Treatment of alcohol delirium].

PMID- 8139247
TI  - [Financial crisis and debates on structure in Berlin hospitals].

PMID- 8139248
TI  - [What is the clinical interest of ultrasound-guided fine needle puncture?].

PMID- 8139249
TI  - [Art in the hospital].

PMID- 8139250
TI  - [Gayety should drive away anxiety. Clown doctors in the pediatric ward].

PMID- 8139251
TI  - [Diagnosis in suspicion of lung embolism].

PMID- 8139252
TI  - [Alternative skin protection].

PMID- 8139253
TI  - [The naked truth of humanness is suffered. The problem of depression proneness].

PMID- 8139254
TI  - [Anxiety and psychological barriers in the care of AIDS patients].

PMID- 8139255
TI  - [On specifics in the position of ambulatory care and similar activities. How
      nurses are able to remain healthy].

PMID- 8139256
TI  - Pathogenic potential of anti-neutrophil cytoplasmic autoantibodies.

PMID- 8139257
TI  - Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical
      implications for diabetes and aging.

PMID- 8139258
TI  - Kinetic expression of endothelial adhesion molecules and relationship to
      leukocyte recruitment in two cutaneous models of inflammation.
AB  - BACKGROUND: Adhesive interactions between circulating leukocytes and endothelium
      is requisite for subsequent leukocyte extravasation at inflammatory sites. These
      adhesive events are mediated by a repertoire of proteins and carbohydrate
      moieties on both leukocyte and endothelial membranes. Understanding the kinetic
      expression of these adhesion molecules during an inflammatory cascade in vivo is
      important for the design and testing of rational therapeutic approaches directed
      at the blockade of adhesion molecule function in inflammatory disease.
      EXPERIMENTAL DESIGN: Two cutaneous inflammatory models were examined using
      healthy rhesus monkeys. Acute cutaneous injury was studied during a 72-hour
      period by intradermal injection of endotoxin (lipopolysaccharide) and subsequent
      biopsy. These tissues were then compared with those obtained from a cutaneous
      delayed-type hypersensitivity reaction (DHR), elicited by intradermal injections
      of mammalian tuberculin in sensitized animals and followed for up to 11 days.
      Expression of E-selectin, P-selectin, VCAM-1, and ICAM-1 was assessed using
      immunohistochemistry and compared with leukocyte localization and
      immunohistochemical expression of interleukin (IL) 1, IL-8 and tumor necrosis
      factor-alpha (TNF-alpha). Finally, relevant adhesion ligands on leukocytes were
      assessed using flow cytometry. RESULTS: The lipopolysaccharide model was
      characterized by early (0.5 hours) and sustained (up to 72 hours) expression of E
      selectin on the superficial dermal vasculature, with maximal expression by 8
      hours. The expression of VCAM-1 was either not detected or minimal. Neutrophil
      localization, as detected by elastase immunoreactivity, paralleled E-selectin
      expression with a 4- to 12-hour lag phase, being maximal by 24 hours. In
      contrast, DHR was characterized by the dual asynchronous expression of both E
      selectin and VCAM-1. Localization of CD2+ lymphocytes, representing the
      predominant cell type recruited, kinetically followed the expression of E
      selectin and VCAM-1, being maximal in number at approximately 48 hours after peak
      expression of both of these endothelial proteins. Neutrophil recruitment in
      lipopolysaccharide-induced injury was associated with immunohistochemical
      localization of TNF-alpha, IL-1, and IL-8, whereas only TNF-alpha was
      consistently detected in DHR. During DHR, blood lymphocyte expression of L
      selectin, VLA-4 (CD49d; alpha chain), and lymphocyte function-associated antigen
      1 (both CD11a (alpha chain) and CD18 (beta chain)) did not change. CONCLUSIONS:
      The results from this study demonstrate that cutaneous inflammatory infiltrates
      of varying cellular compositions are associated temporally and spatially with
      unique patterns of endothelial adhesion molecule and cytokine expression.

PMID- 8139259
TI  - Expression of matrix metalloproteinase-2 and -9 during early human wound healing.
AB  - BACKGROUND: During wound healing, keratinocytes detach from the basement membrane
      and migrate to cover the exposed connective tissue. Subsequently, the wound clot
      is degraded gradually and replaced by the epithelial cells and the granulation
      tissue. Both of these processes are likely to be affected by matrix-modifying
      enzymes. Type IV collagenases are members of the matrix metalloproteinase family
      (MMP), which are known to degrade several matrix components. The aim of this
      study was to investigate the expression of MMP-2 and MMP-9 (72-kd and 92-kd type
      IV collagenases, respectively) during early human wound healing. EXPERIMENTAL
      DESIGN: Experimental wounds were created in human oral mucosa and biopsies were
      taken 1, 3, and 7 days after wounding. In situ hybridization on paraffin sections
      was used for the detection of messenger RNAs coding for MMP-2 and MMP-9, and the
      secretion of MMPs into the oral cavity after wounding was followed by zymography.
      Regulation of MMP-2 and MMP-9 expression by cytokines was studied using cultured
      mucosal keratinocytes, gingival fibroblasts, and wound granulation tissue
      fibroblasts. RESULTS: By in situ hybridization, the expression of MMP-2 was
      localized in the connective tissue fibroblasts and endothelial cells during all
      phases of wound healing. Mucosal epithelium was practically negative for MMP-2
      expression. MMP-9 messenger RNA was found in mucosal epithelium on days 1, 3, and
      7. A strong signal was localized in basal and suprabasal cell layers in the
      nonwounded area, while only the basal cell layer was MMP-9 positive in the
      migrating epithelial sheet. Seven days after wounding, granulation tissue
      exhibited an unusually strong signal for MMP-9 messenger RNA. Wound fluid
      contained mainly MMP-9, the amount of which was highest in two- to four-day-old
      secretions. None of the cytokines tested (transforming growth factor beta-1,
      interleukin-1 beta, basic fibroblast growth factor, tumor necrosis factor-alpha,
      interferon-gamma) were able to regulate MMP-2 expression in cultured wound
      fibroblasts. However, keratinocyte MMP-9 production was enhanced by interleukin-1
      beta, transforming growth factor beta-1, and tumor necrosis factor-alpha.
      CONCLUSIONS: During wound healing, MMP-9 is suggested to be involved in
      keratinocyte migration and granulation tissue remodelling. Expression of MMP-2
      remains stable during wound healing.

PMID- 8139260
TI  - L-Tryptophan in supraphysiologic concentrations stimulates collagenase gene
      expression in human skin fibroblasts.
AB  - BACKGROUND: Collagenase plays a critical role in regulating connective tissue
      breakdown in physiologic and pathologic processes. The expression of collagenase
      is modulated by a variety of biologic and pharmacologic agents. L-tryptophan is
      an essential amino acid with diverse biologic effects not shared by other amino
      acids. EXPERIMENTAL DESIGN: In this study, we examined the effects of L
      tryptophan on collagenase gene expression in normal human skin fibroblasts using
      Northern hybridizations and transient transfection assays. RESULTS: The results
      indicate that L-tryptophan at supraphysiologic concentrations caused a marked
      increase in collagenase gene expression. The increase in collagenase mRNA levels
      was reversible, time- and dose-dependent, and was accompanied by enhancement of
      procollagenase synthesis and secretion. Parallel accumulation of mRNA for tissue
      inhibitor of metalloproteinase was also noted, whereas stromelysin mRNA levels
      remained undetectable. The enhancement of collagenase mRNA was specific for L
      tryptophan, and was abrogated by alpha-amanitin or dexamethasone. The apparent
      half-life of collagenase mRNA transcripts was similar in cultures exposed to
      interleukin-1 beta or L-tryptophan. In contrast to interleukin-1 beta, L
      tryptophan-induced increase in collagenase mRNA was not preceeded by expression
      of c-jun or c-fos. Transient transfection of human skin fibroblasts with a
      collagenase promoter, chloramphenicol acetyl transferase construct indicated
      marked dose-dependent increase in promoter activity with L-tryptophan.
      CONCLUSIONS: These results demonstrate that L-tryptophan in supraphysiologic
      concentrations is a potent inducer of collagenase gene expression in vitro at a
      transcriptional level by human skin fibroblasts.

PMID- 8139261
TI  - Transforming growth factor-beta promotes deposition of collagen VII in a modified
      organotypic skin model.
AB  - BACKGROUND: Anchoring fibrils, which consist mainly of collagen VII, form a three
      dimensional network below stratified squamous epithelia thus attaching the
      epithelial basement membrane to the underlying connective tissue. In skin,
      collagen VII is mainly produced by keratinocytes, and in vitro findings of
      keratinocyte-fibroblast cocultures suggest that mesenchymal-epithelial signaling
      plays a major role in the regulation of its expression. The matrix cytokine
      transforming growth factor-beta (TGF-beta) is a candidate mediator of such
      interactions, and exogenous TGF-beta has been shown to stimulate collagen VII
      expression in vitro. In the present study, the role of TGF-beta and other growth
      factors as mediators of mesenchymal-epithelial interactions in the regulation of
      collagen VII synthesis and deposition was investigated. EXPERIMENTAL DESIGN: The
      synthesis of collagen VII in monolayer cultures of normal human skin cells and in
      an organotypic skin equivalent system was investigated by indirect
      immunofluorescence staining. The role of soluble factors in collagen VII
      regulation was examined in a two-compartment coculture system, and the effect of
      medium conditioned by cocultures was tested on monocultures. Neutralizing
      antibodies to TGF-beta 2 were used to establish the relevance of this growth
      factor in the regulation of collagen VII synthesis. Modified skin equivalent
      cultures were constructed by cultivating an epithelium on top of devitalized
      human dermis deprived of the basement membrane. RESULTS: TGF-beta 2 was found to
      be a major autocrine or paracrine stimulator of collagen VII synthesis in
      cocultures. Incubation of the cultures with neutralizing antibodies to this
      growth factor abolished expression of collagen VII almost completely. Among other
      putative regulators of extracellular matrix metabolism, such as insulin-like
      growth factor, basic fibroblast growth factor, platelet-derived growth factor,
      epidermal growth factor, and calcium, insulin-like growth factor and calcium
      stimulated collagen VII synthesis by keratinocytes, but the extent was clearly
      less than by TGF-beta. Fibroblasts did not respond to either growth factor.
      However, experiments with fibroblasts grown on a keratinocyte-derived
      extracellular matrix suggested that collagen VII synthesis by fibroblasts is
      enhanced by matrix-mediated stimuli. A modified organotypic skin equivalent
      proved to be a suitable model to study the expression and deposition of basement
      membrane components. Collagen VII was expressed by basal keratinocytes after 3
      weeks in culture under serum-free conditions. Its deposition at the
      dermoepidermal junction, however, depended on the addition of TGF-beta.
      CONCLUSIONS: TGF-beta is an important mediator of mesenchymal-epithelial
      interactions regulating collagen VII expression, and the deposition of collagen
      VII at the dermoepidermal interface is promoted by this growth factor. TGF-beta
      is a candidate factor for stabilization of the dermoepidermal junction in vivo
      during wound healing and in conditions where the junction zone is pathologically
      altered, e.g., dystrophic epidermolysis bullosa.

PMID- 8139262
TI  - Expression of genes encoding connective tissue proteins in androgen-dependent
      SC115 tumors after androgen removal.
AB  - BACKGROUND: Shionogi carcinoma 115 (SC115) is an androgen-dependent medullary
      carcinoma with a compact cell pattern. When SC115 tumors grow in androgen
      depleted hosts, spindle-shaped and round cells with abundant cytoplasm develop.
      These cells originate from the SC115 cells (Kitamura et al., Cancer Res
      1979;39:4717; Terada et al., Lab Invest 1987;57:186). EXPERIMENTAL DESIGN: We
      investigated whether these spindle-shaped and round cells expressed mRNAs of
      noncollagenous connective tissue proteins, which are expressed by normal spindle
      shaped cells and normal chondrocytes in developing bones. The expression and
      localization of osteonectin (OSN), osteopontin (OSP), matrix Gla protein (MGP),
      and osteocalcin (OSC) were determined by Northern blotting and in situ
      hybridization. RESULTS: No mRNA signals of these proteins were detectable in
      SC115 medullary carcinoma cells growing in DS mice that had been castrated but
      received injections of testosterone propionate. However, when the injection of TP
      was stopped, spindle-shaped and round cells with abundant cytoplasm developed.
      The former expressed OSN and OSP signals, and the latter OSN, OSP, and MGP
      signals. CONCLUSIONS: Transcripts of OSN, OSP, and MGP were expressed by some
      SC115-derived cells during the differentiation events that occurred after
      androgen removal. These results provide molecular biologic evidence that a tumor
      of epithelial origin can progress along the connective tissue differentiation
      pathway.

PMID- 8139263
TI  - Enhanced proteolytic activity is responsible for the aberrant morphogenetic
      development of SV40-immortalized normal human salivary gland cells grown on
      basement membrane components.
AB  - BACKGROUND: A reconstituted basement membrane extract, Matrigel, is a potent
      inducer of cell growth and differentiation in vitro in a number of cell types. In
      this study, we examined the effect of Matrigel on the morphogenesis of cultured
      normal human salivary gland cells. EXPERIMENTAL DESIGN: SV40-immortalized normal
      human salivary gland-cell clones with duct- (NS-SV-DC) or myoepithelial phenotype
      (NS-SV-MC), which had been established in our laboratory (Azuma M, et al., Lab
      Invest, 1993;69:24-42), were cultured on Matrigel in serum-free culture
      conditions, and then morphogenetic behavior of cell clones was examined. RESULTS:
      When cell clones were seeded on Matrigel, they formed round or zonal clusters on
      day 1; however, they failed to develop into a salivary gland morphogenesis.
      Semithin sections of cell clones cultured on Matrigel exhibited multicellular
      aggregates on day 1, whereas on days 2 and 3, these cells lost both cell-Matrigel
      and cell-cell interactions and eventually entered crisis. In an attempt to
      understand the mechanism involved in this phenomenon, we investigated proteolytic
      enzymes and their inhibitors secreted by cell clones. Although cell clones
      produced almost identical levels of gelatinases, they released increased amounts
      of plasminogen activators as compared with a neoplastic human salivary gland cell
      line, which had already been demonstrated to differentiate into acinar cells when
      cultured on Matrigel. Obvious difference of expression level of tissue inhibitor
      of metalloproteinases-1 was not observed in these cells, however, NS-SV-DC
      produced a relatively small amount of endothelial-type plasminogen activator
      inhibitor as compared with NS-SV-MC. Neutralization of excess plasminogen
      activators by exogenously added serine protease inhibitors corrected the aberrant
      in vitro morphogenesis of NS-SV-DC, but not of NS-SV-MC, and allowed NS-SV-DC to
      form glandular-like structures.

PMID- 8139264
TI  - Expression of eosinophil-granule major basic protein messenger ribonucleic acid
      in placental X cells.
AB  - BACKGROUND: The human eosinophil-granule major basic protein (MBP) is a 13.8
      kilodalton cationic polypeptide constituting the core of the eosinophil granule.
      MBP is cytotoxic to parasites and numerous mammalian cells and is a potent
      secretagogue for platelets, basophils, mast cells, and neutrophils.
      Concentrations of a molecule immunochemically similar to eosinophil granule MBP
      are present in maternal plasma, and MBP has been localized by immunofluorescence
      to placental X cells. EXPERIMENTAL DESIGN: To determine whether X cells produce
      MBP, the expression of MBP messenger RNA (mRNA) was investigated in placentas by
      Northern blot analyses and by in situ hybridization with 35S-labeled RNA probes.
      RESULTS: Northern blot analyses of RNA from placental septa and villi showed the
      existence of a 1.0-kb RNA band that hybridized with the MBP anti-sense probe; no
      MBP mRNA was detected in whole blood of normal or pregnant women or in cord
      blood. Analyses of placentas by in situ hybridization showed MBP mRNA in X cells
      of placental septa and anchoring villi, but not in other cellular elements such
      as syncytiotrophoblasts, cytotrophoblasts, villous stromal cells, and fetal
      endothelial cells. RNase pretreatment abolished X-cell hybridization signals;
      treatment of sections with an excess of nonradiolabeled anti-sense RNA also
      blocked binding of the 35S-labeled anti-sense RNA probe. Additional evidence
      supporting the production of MBP by X cells was obtained using a combination of
      in situ hybridization and immunofluorescence, which showed colocalization of MBP
      and its mRNA. CONCLUSIONS: The presence of MBP mRNA and MBP protein in placental
      X cells indicates that X cells synthesize this biologically active molecule.

PMID- 8139265
TI  - Qualitative and quantitative histopathology in transitional cell carcinomas of
      the urinary bladder. An international investigation of intra- and interobserver
      reproducibility.
AB  - BACKGROUND: Histopathologic, prognosis-related grading of malignancy by means of
      morphologic examination in transitional cell carcinomas of the urinary bladder
      (TCC) may be subject to observer variation, resulting in a reduced level of
      reproducibility. This may confound comparisons of treatment results. Using
      objective, unbiased stereologic techniques and ordinary histomorphometry, such
      problems may be solved. EXPERIMENTAL DESIGN: A study of 110 patients with
      papillary or solid transitional cell carcinomas of the urinary bladder in stage
      Ta through T4 was carried out, addressing reproducibility of both qualitative and
      quantitative grading methods. Grading of malignancy was performed by one observer
      in Japan (using the World Health Organization scheme), and by two observers in
      Denmark (using the Bergkvist system). A "translation" between the systems, grade
      for grade, and kappa statistics were used in evaluating the reproducibility.
      Unbiased estimates of nuclear mean volume, nuclear mean profile area, nuclear
      volume fraction, nuclear profile density index, and mitotic profile density index
      were obtained twice in 55 of the studied cases by one observer in Japan and one
      in Denmark, using a random, systematic sampling scheme. RESULTS: The results were
      compared by bivariate correlation analyses and Kendall's tau. The international
      interobserver reproducibility of qualitative gradings was rather poor (kappa =
      0.51), especially for grade 2 tumors (kappa = 0.28). Likewise, the interobserver
      agreement on the Bergkvist scheme was poor (kappa = 0.43). On the other hand was
      the interobserver agreement on invasion high (kappa = 0.75). The intraobserver
      reproducibility of the quantitative histopathologic variables was excellent in
      both Japan and Denmark for estimates of nuclear mean volume (r = 0.93), for
      nuclear mean profile area (0.78 < r < 0.83), and for nuclear profile density
      index (0.85 < r < 0.89), whereas the reproducibility for nuclear volume fraction
      was somewhat poorer (0.68 < r < 0.64). The slopes of the correlation lines were
      not significantly different from unity. Estimates of mitotic profile density
      index also showed acceptable intraobserver reproducibility (Kendall's tau >
      0.53). CONCLUSIONS: The international, interobserver reproducibility of the
      quantitative estimators yielded similar results for all histopathologic variables
      investigated, except for nuclear volume fraction (r = 0.54). This can probably be
      related to the manual design of the sampling scheme and may be solved by
      introducing a motorized object stage in the systematic selection of fields of
      vision for quantitative measurements. However, the nuclear mean size estimators
      are unaffected by such sampling variability. The results obtained in this study
      stress the need for objective, quantitative histopathologic techniques
      substituting qualitative, subjective methods in prognosis-related grading of
      malignancy.

PMID- 8139266
TI  - Pathology and localization of simian immunodeficiency virus in the reproductive
      tract of chronically infected male rhesus macaques.
AB  - BACKGROUND: Despite the fact that human immunodeficiency virus (HIV) is
      transmitted by sexual contact, the biology of this mode of transmission remains
      largely undefined. HIV is present in semen in both cell-free and cell-associated
      forms and can be isolated from asymptomatic individuals and AIDS patients. The
      source of HIV in semen and the target cells for HIV transmission to men are
      unknown. Epidemiologic studies have shown that in men, the presence of an intact
      foreskin is associated with increased risk of HIV infection. EXPERIMENTAL DESIGN:
      The reproductive tracts from 13 chronically simian immunodeficiency virus (SIV)
      infected adult male rhesus macaques were examined for this study. Routine
      histologic examination was undertaken to characterize the reproductive tract
      pathology. In situ hybridization and immunohistochemistry were used to localize
      SIV-infected cells and determine the immunophenotype of inflammatory infiltrates.
      RESULTS: SIV-infected cells (macrophages, T cells) were found at all levels of
      the reproductive tract and were commonly associated with inflammatory lesions.
      Infected cells were found most consistently in the epididymis. In one animal, SIV
      infected cells (presumably Langerhans cells) were present in the stratified
      squamous epithelium of the foreskin. Testicular atrophy and degeneration were
      relatively common findings. The most common lesion in the accessory glands was
      mild lymphocytic inflammation. In addition, atrophy of the glandular elements and
      interstitial fibrosis in the prostate gland were found. One animal had a
      granulomatous epididymitis with multinucleate giant cells that may have been a
      primary SIV lesion. CONCLUSIONS: The reproductive tract pathology in chronically
      SIV-infected male rhesus macaques and AIDS patients is similar. SIV-infected
      cells can be found at all levels of the male rhesus macaque reproductive tract
      and SIV can infect cells in the mucosal epithelium of the foreskin. This latter
      finding indicates that target cells for HIV transmission may be present in the
      foreskin epithelium of uncircumcised men.

PMID- 8139267
TI  - Murine hepatitis caused by lymphocytic choriomeningitis virus. I. The hepatic
      lesions.
AB  - BACKGROUND: The hepatitis that occurs after adult mice are infected with
      lymphocytic choriomeningitis (LCM) virus is immune mediated, although the details
      of the pathogenetic mechanisms are largely unknown. To better understand the
      sequence of events leading to alterations typical for hepatitides with
      immunopathogenesis, livers of immunocompetent mice infected with LCM virus were
      examined. EXPERIMENTAL DESIGN: Virus replication and histopathology in the livers
      and concentrations of liver enzymes in the sera of C57BL/6 mice were followed
      from day 3 through day 14 after intraperitoneal infection with 10(6) mouse
      infectious units of LCM virus. Histologic, histochemical, immunohistologic, and
      in situ hybridization methods were used to determine the cells involved in the
      inflammatory process. RESULTS: Infectious virus rose to 10(9) mouse infectious
      units/g of liver by day 7 and declined thereafter. Viral RNA and antigen were
      localized in foci of hepatocytes and in Kupffer and endothelial cells of the
      sinusoids. Disseminated spotty necroses, steatosis, a marked sinusoidal reaction,
      and lobular and (later) periportal mononuclear infiltrates were observed. In the
      infiltrates, T cells predominated followed by macrophages and NK cells; the
      number of B and plasma cells rose moderately. Among T lymphocytes the CD8+ cells
      increased preferentially, and the CD4/CD8 ratio changed from 1.7 to 0.3. Other
      features were major histocompatibility complex antigen expression on hepatocytes,
      enhanced immunocytochemical evidence of fibronectin and ICAM-1 in sinusoids, and
      deposition of immunoglobulin, complement, and fibrinoid. Changed activities of
      liver enzymes and bilirubin levels paralleled the pathologic alterations.
      CONCLUSIONS: Although CD8+ T cells seem to be central in the pathogenesis of LCM
      hepatitis, probably more than one immunopathologic mechanism is operative.

PMID- 8139268
TI  - Oxidative stress induces adult T cell leukemia derived factor/thioredoxin in the
      rat retina.
AB  - BACKGROUND: Adult T cell leukemia derived factor (ADF), originally defined as an
      interleukin-2 receptor inducer, is a human thioredoxin homolog. ADF/thioredoxin
      has several biologic functions, such as defense against cellular damage, activity
      to scavenge oxidative stress by hydrogen peroxide radicals and cytokine-like
      properties. We hypothesized that under certain conditions, ischemia followed by
      reperfusion and/or light exposure, ADF may be induced in the retina. EXPERIMENTAL
      DESIGN: To test this hypothesis, we prepared experimental animal models in which
      oxidative stress could be applied to the retina. In the present study, we
      examined ADF expression in the rat retina using temporary ischemia and
      reperfusion, and photodynamic retinal vascular thrombosis by immunohistochemical
      and Western blotting methods. RESULTS: ADF expression was strongly induced in the
      retinal pigment epithelial cells after 2 hours of ischemia followed by 2, 24, or
      48 hours of reperfusion. ADF was also expressed in retinal pigment epithelial
      cells as early as 3 hours after light exposure followed by rose bengal injection,
      and this expression increased with time. Western blotting data showed that ADF
      expression increased in the retinal pigment epithelial cells in the experimental
      group, as compared with the control group. These results indicate that ADF is
      actively induced in retinal pigment epithelial cells upon oxidative stress.
      CONCLUSIONS: ADF induction in retinal pigment epithelial cells may be involved in
      the defense mechanism against cellular damage caused by active oxygen species
      generated during oxygen stress to the retina.

PMID- 8139269
TI  - Colocalization of myocardial fibrosis and inflammatory cells in rats.
AB  - BACKGROUND: Left ventricular overload and aging lead to an increase in fibrosis
      in the rat cardiac interstitium. The relationship between fibrosis, fibroblast
      activity, and inflammatory cell infiltration, was explored in spontaneously
      hypertensive rats (SHR) and Wistar controls. EXPERIMENTAL DESIGN: The left
      ventricle of three groups of eight SHR and eight Wistar controls hearts were
      sectioned for light microscopy, immunohistochemistry, and in situ hybridization
      with a cDNA probe encoding the murine alpha 1 chain of type I collagen. Fibrosis
      was measured morphometrically. Monoclonal antibodies directed against Ia antigen,
      CD8+ cytotoxic, CD4+ helper lymphocytes and monocyte/macrophages were used to
      localize and quantify the inflammatory cells. RESULTS: In 2-month-old rats, with
      nearly normal interstitial cardiac tissue, fibroblasts expressing collagen mRNA
      were located around coronary vessels. The areas of fibrosis and interstitial
      cellular infiltration were more extensive in 22-month-old rats than in 12-month
      old rats and greater in SHR than in Wistar. Fibroblasts expressing collagen mRNA
      were mainly found at the border between fibrosis and myocytic cells, and were
      always colocalized with lymphocytes and macrophages. The interstitial areas of
      fibrosis and collagen I expressing fibroblasts had the same pattern of
      infiltrating cells in normotensive rats than in SHR. Fibrosis and the density of
      macrophages and CD4+ lymphocytes were correlated. CONCLUSIONS: Thus, fibroblast
      activity could be closely related to the presence of lymphocytes and macrophages
      in the myocardium of spontaneously hypertensive and aged rats.

PMID- 8139270
TI  - Observation on the curative effect of acupuncture on type I allergic diseases.
AB  - In a comparative study on treatment of type I allergic diseases, acupuncture and
      desensitization therapies were performed in 143 cases. The results showed that
      acupuncture therapy had an extensive and remarkable action against type I
      allergic reaction. The curative effect was higher in the acupuncture group than
      in the desensitization group in allergic asthma, allergic rhinitis and chronic
      urticaria.

PMID- 8139271
TI  - Observation of therapeutic effect in 50 cases of chronic renal failure treated
      with rhubarb and adjuvant drugs.
AB  - Treatment of chronic renal failure with rhubarb and adjuvant drugs combined with
      other appropriate measures alleviates the suffering of the patients and improves
      the quality of their survival. Most patients can take care of themselves after
      treatment, and some can engage in half-day work. The treatment prolongs the life
      of the patient, and reduces medical expenses. It is of definite social and
      economic benefit, and conforms with China's conditions. Except for very severe
      cases whose blood creatinine exceeds 884 mumol/L, it can be given to all
      patients. It can also be used as a transitional measure before more radical
      therapies may be instituted.

PMID- 8139272
TI  - Treatment of stomatological complications in 31 cases of acute leukemia with
      Chinese herbal drugs.
AB  - The authors treated 31 cases of stomatological complications of acute leukemia
      with Chinese herbal drugs. It was found that the prevalence of oral mucosal
      ulcers was the highest (80%) in acute lymphocytic leukemia, and the prevalence of
      gingival swelling was the highest (44%) in acute monocytic leukemia. In
      accordance with symptom differentiation, Qing Wei San (Powder for Clearing
      Stomach-heat) with modifications was administered in cases of exuberance and Yu
      Nu Jian (Gypsum Decoction) with modifications was administered in cases of
      deficiency, plus gargling solution and hemostatic powder for external use. As a
      result, 7 cases (22.6%) were markedly effective, and 19 cases (61.3%) effective,
      the total effective rate being 83.9%. The authors believed that stomatological
      complications of leukemia were due to insufficiency of yin and blood in the body
      or to the toxicity and heat of anti-neoplastic medication, and the Chinese herbal
      drugs were to replenish yin and clear the heat.

PMID- 8139273
TI  - A comparative clinical study on prevention and treatment with selected
      chronomedication of leukopenia induced by chemotherapy.
AB  - During the period of therapy, leukopenia induced by chemotherapy was less severe
      and was cured more rapidly in the selected chronomedication group (CMG) than in
      the routine medication group (RMG). The incidence of leukopenia was markedly
      lower in CMG (12.9%) than in RMG (48.4%), and the rate of uneventful completion
      of chemotherapy was also higher in CMG (96.8%) than in RMG. These results suggest
      that selected chronomedication may be beneficial to the successful completion of
      chemotherapy in patients with malignant tumor.

PMID- 8139274
TI  - Treatment of periarthritis humeroscapularis with acupuncture and acupoint
      blocking.

PMID- 8139275
TI  - Treatment of acute lumbar sprain with acupuncture at Fuyang (UB 59).

PMID- 8139276
TI  - Treatment with cone moxibustion of chemotherapeutic leukocytopenia in 114 cases.

PMID- 8139277
TI  - Combination of traditional Chinese and Western medicine in treating acute
      posterior multifocal placoid pigment epitheliopathy.

PMID- 8139278
TI  - Experimental research on treatment of hypertension with acupuncture.
AB  - The effects of acupuncture on blood pressure, microcirculation of bulbar
      conjunctiva and hemorheology in spontaneous hypertensive rats (SHRs) were
      observed. The mechanism of acupuncture to lower blood pressure is discussed from
      the viewpoint of microcirculation and hemorheology. SHRs and Wistar rats of both
      sexes weighing about 250g were divided into three groups: 1. Acupuncture group of
      15 SHRs, in which Quchi (LI 11) and Taichong (Liv 3), Hegu (LI 4) and Zusanli (St
      36) were selected and punctured twice a day with the needle retained for 15
      minutes and the reducing method by twisting and twirling the needle used, 15 days
      constituting a course; 2. Control group of 10 SHRs; 3. Control group of 10 normal
      Wistar rats. All rats in groups 2 and 3 were treated in the same way as in Group
      1 except for the acupuncture. It was found that the morphology and blood flow of
      bulbar conjunctiva microcirculation in SHRs were obviously abnormal: the
      capillaries with blood flow were reduced in number, the arterioles were spasmodic
      and of smaller diameter, the venules were dilated due to blood stasis which
      showed a slow granular flow of blood, the blood viscosity was increased,
      hematocrit increased, and the time for RBC electrophoresis prolonged. The blood
      was in a state of high viscosity, high concentration and high aggregation. After
      acupuncture treatment the blood pressure not only fell, but the morphology and
      blood flow of bulbar conjunctiva microcirculation and the hemorheology of SHRs
      all improved remarkably.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139279
TI  - Effect of qingyangshen on hippocampal alpha- and beta-tubulin gene expression
      during kainic acid induced epileptogenesis.
AB  - Using alpha- and beta- tubulin cDNA Probes and Northern blot hybridization
      technique, we analyzed the effect of intraperitoneally injected Qingyangshen
      (QYS), a traditional Chinese medicine with antiepileptic property, and
      diphenylhydrantoin sodium (DPH) on hippocampal alpha- and beta-tubulin gene
      expression during kainic acid (KA) induced chronic seizures. It was found that:
      1) thirty days after intraperitoneal injection of KA, alpha- and beta-tubulin
      mRNAs in animals showing chronic seizures increased 3.02 +/- 1.05 and 4.07 +/-
      1.32 times respectively compared with control; 2) neither QYS (15 mg/kg, q.o.d. x
      6) nor DPH (50 mg/kg, q.o.d. x 6), when used separately, could inhibit the above
      mentioned effect of KA; 3) when QYS (15 mg/kg, q.o.d. x 6) and DPH (50 mg/kg,
      q.o.d. x 6) were given in combination, the long-term increase in tubulin gene
      expression induced by KA was significantly reduced, with alpha- and beta-tubulin
      mRNAs being decreased to 0.44 +/- 0.08 and 0.50 x 0.10 times of corresponding
      values in animals treated with KA alone. The results indicate that the mechanism
      of antiepileptic effect of QYS is at least partially related to the inhibition of
      tubulin synthesis and subsequent reduction in mossy fiber sprouting and
      neosynaptogenesis.

PMID- 8139280
TI  - Study on the therapeutic effects of traditional Chinese drugs in experimental
      glomerulonephritis.

PMID- 8139281
TI  - Treatment of strain of the infrapatellar fat pad by manipulation--observation of
      therapeutic effect in 117 cases.
AB  - The present group comprises 117 cases of strain of the infrapatellar fat pad. The
      treatment effected a 100% cure in the mild and moderate types of the cases. In
      the severe cases suffering from such accompanying conditions as traumatic
      arthritis, the rate of effectiveness reached 100%, with all symptoms and signs
      becoming markedly alleviated. The treatment is considered a method of the first
      choice in handling strain of the infrapatellar fat pad, and also a good method
      for treating traumatic arthritis of the knee and malacia of the patella.

PMID- 8139282
TI  - Application of finger pressure to ankle sprains.

PMID- 8139283
TI  - Recent advances in studies on traditional Chinese anti-aging materia medica
      (continued).

PMID- 8139284
TI  - Lectures on Chinese pharmacology--the origin and characteristics of Chinese
      pharmacology.

PMID- 8139285
TI  - Myelodysplasia and acute megakaryoblastic leukemia in Down's syndrome.
AB  - In this report we describe the clinical and hematologic features of 23 cases of
      myelodysplasia (MDS) or acute megakaryoblastic leukemia (AMKL) occurring in
      Down's syndrome. MDS was characterized by thrombocytopenia, abnormal
      megakaryocytopoiesis, megakaryoblasts (< 30%) in the marrow and abnormal
      karyotype, the most common of which was trisomy 8, found in 7/15 patients with
      MDS. Three of five patients achieved a complete remission with low dose cytosine
      arabinoside, vincristine and retinyl palmitate. The high cure rate and the
      distinctive features of the leukemic process in these cases suggest that this
      type of MDS and AMKL are unique to patients with Down's syndrome.

PMID- 8139286
TI  - Immunophenotyping of acute lymphoblastic leukaemia in Madras, India.
AB  - At the Cancer Institute, Madras, India, we have performed immunophenotyping in
      125 untreated cases of acute lymphoblastic leukaemia using a panel of 16
      monoclonal antibodies and the avidin-biotin immunoperoxidase technique in a
      haematology autoanalyser (Technicon Hi system). Our results demonstrate a marked
      difference in the phenotypic pattern of ALL compared to Western countries, the
      predominant finding being a relative excess of T-ALL and a paucity of C-ALL
      cases. Age distribution of C-ALL reveals a peak at 2-6 years in paediatric ALL
      cases.

PMID- 8139287
TI  - Involvement of oxygen radicals in the differentiation of rat myelomonocytic
      leukemia cells in vitro and in vivo.
AB  - We have found that LPS induces the differentiation of an LPS-resistant subline
      (LR) of rat myelomonocytic leukemia cell line, c-WRT-7, in vivo, which are
      resistant to the differentiation inducing effects of LPS in vitro. Furthermore,
      we have found that the differentiation of LR cells induced by LPS is inhibited by
      superoxide dismutase, which is one of radical scavengers. Accordingly, we have
      examined the differentiation inducing effects of xanthine oxidase, a potential
      source of oxygen radicals, on LR cells in vitro and in vivo. Xanthine oxidase
      induced the differentiation of LR cells into macrophage-like cells in vitro; and
      superoxide dismutase inhibited the differentiation of LR cells induced by
      xanthine oxidase both in vitro and in vivo. These results suggest that oxygen
      radicals are involved in the differentiation inducing effects of LPS.

PMID- 8139288
TI  - Effects of herbimycin A and its derivatives on growth and differentiation of Ph1
      positive acute lymphoid leukemia cell lines.
AB  - The molecular basis of the Philadelphia chromosome (Ph1) is a structurally
      altered c-abl (bcr/abl) gene which encodes an abnormally large protein with
      protein tyrosine kinase activity. Herbimycin A, an inhibitor of tyrosine kinase,
      preferentially inhibited the growth of Ph1-positive acute lymphoid leukemia (ALL)
      cell lines, as well as Ph1-positive chronic myeloid leukemia (CML) cell lines.
      Although noncytotoxic concentrations of herbimycin A induced erythroid
      differentiation of two CML-derived cell lines, K562 and KU812, in a previous
      study, the differentiation-inducing effect of herbimycin A on Ph1-positive ALL
      cell lines was less strong. Herbimycin A enhanced some differentiation-associated
      properties of one Ph1-positive ALL cell line, L2, but the effect of herbimycin A
      on the other Ph1-positive ALL cell lines was cytotoxic rather than cytostatic
      (differentiation-inducing). Several derivatives of herbimycin A were synthesized
      and their effects on the cell proliferation of Ph1-positive CML and ALL cell
      lines were examined. The sensitivities of the Ph1-positive cell lines to
      herbimycin A derivatives were different from the data on the rat kidney cell line
      infected with Rous sarcoma virus (v-src) derived from a previous study,
      suggesting bcr/abl kinase may differ in sensitivity from other tyrosine kinases.
      Moreover, the sensitivities of the ALL cell lines were not the same as those of
      the CML cell lines. These results suggest that a specific inhibitor of bcr/abl
      kinase could be an effective antileukemic agent against Ph1-positive CML or ALL.

PMID- 8139289
TI  - Two possible metabolic blocks in DNA synthesis that could be mutagenic.

PMID- 8139290
TI  - Hypercalcemia in acute lymphoblastic leukemia.

PMID- 8139291
TI  - Authorizing the body: scientific medicine and The scarlet letter.

PMID- 8139292
TI  - The social text as body: images of health and disease in three recent feminist
      utopias.

PMID- 8139293
TI  - The art of the suture: Richard Selzer and medical narrative.

PMID- 8139294
TI  - The neurobiology of the obscene: Henry Miller and Tourette syndrome.

PMID- 8139296
TI  - A grief observed: the paintings of Ellen Berman.

PMID- 8139295
TI  - Love unto death: Fanny Burney's "Narrative of the last illness and death of
      General d'Arblay" (1820).

PMID- 8139297
TI  - Risk of entering nursing homes for long versus short stays.
AB  - Research on the risk of nursing home use has generally not distinguished between
      risk for long versus short stays. This paper presents an analysis of data from
      the 1982-84 National Long-Term Care Surveys to identify characteristics of
      disabled persons that predicted one or the other type of stay. Measures that are
      recognized to be strong predictors of nursing home use in general, such as
      dependencies in activities of daily living and cognitive impairment, were not
      significantly associated with admission for short stays. Results from the
      multivariate analysis were also used to make projections of lifetime risk of long
      and short stays. Approximately one-third of lifetime nursing home risk applies to
      stays of 90 days or less.

PMID- 8139298
TI  - The quality of breast cancer care in local communities: implications for health
      care reform.
AB  - Despite many advances in the treatment of breast cancer during the last decade,
      many breast cancer patients still do not receive appropriate treatment. The year
      2000 cancer control objectives for the nation require a 50% decrease in breast
      cancer mortality. This goal cannot be achieved unless appropriate care is
      provided to all women with breast cancer. This study examines the role of patient
      characteristics, health insurance, physician characteristics, competition and
      local environment factors on the quality of care provided by physicians to breast
      cancer patients. Developed from a theoretical model of physician behavior, an
      empirical model was tested to demonstrate how these factors affect the quality of
      care provided for two specific breast cancer practice patterns: 1) whether a two
      step surgical technique was performed and, 2) whether postmastectomy
      rehabilitation and/or education was provided. Data from the National Cancer
      Institute Community Cancer Care Evaluation, from 1985-1986 were used and included
      information about the inpatient and outpatient care provided to 3,972 women with
      local or regional stage breast cancer from local communities across the United
      States. Multivariable regression results indicate older patients were
      significantly less likely to receive appropriate care for both surgical and
      rehabilitation practice patterns studied: patients 80 years and older were two to
      three times less likely to receive appropriate care. However, effects for other
      variables differed for the two practice patterns studied: competition had a
      significant positive impact on surgical care (Odds ratio (OR) = 1.37, P < 0.01),
      but a negative impact on rehabilitation care (OR = 0.76, P < 0.01), and only
      having Medicaid coverage had a significant positive impact on whether
      rehabilitation care was provided (OR 1.93, P < 0.03), but no effect for whether a
      two-step procedure was performed. The results from this study have implications
      for program design and policy initiatives aimed at assuring equity in access to
      treatment for older women. Moreover, the differential effects of competition on
      these breast cancer practice patterns may have implications for health care
      reform efforts that rely exclusively on competitive models without performance
      based incentives to ensure appropriate care.

PMID- 8139299
TI  - The effect of gender and race on the measurement properties of the CES-D in older
      adults.
AB  - Having observed a three-fold difference in the prevalence of significant symptoms
      of depression among four race-gender groups of elderly adults attending an urban
      primary care practice, we investigated the extent to which these differences
      might be explained by variability in the measurement properties of the Centers
      for Epidemiologic Studies depression scale (CES-D). Although the internal
      consistency of the CES-D was acceptable for all groups, 5% of our patients were
      excluded for inability to complete the minimum required number of CES-D items,
      and nearly 40% of patients required response imputation for the allowable one to
      four items that they could not answer. Imputation was most frequently required
      for items tapping positive affect. Principal components factor analysis was
      performed separately for respondents answering all items and for respondents with
      imputed values. In both analyses we found important race-gender differences in
      factor structure. Moreover, the factor structure for those with imputed values
      was markedly different from that of respondents answering all items, including a
      dissolution of the positive affect dimension. Neither the race-gender differences
      in factor structure nor the differences among those with and without imputed data
      were resolved by eliminating respondents with poor education, cognitive
      impairment, or alcoholism, or by varying the assumptions for data imputation.
      However, the disparities in factor structure were essentially resolved by
      eliminating five CES-D items, suggesting the need to modify the CES-D in
      populations like ours. Although eliminating these five items results in a more
      pure factor structure, it does not resolve the differences in prevalence of
      depressive symptoms. These differences may, however, be partially due to
      differential response tendencies among the race-gender groups.

PMID- 8139300
TI  - Measuring the necessity of medical procedures.
AB  - This is a report on the extension of the concept of the appropriateness of a
      procedure to the necessity, or crucial importance, of that procedure. To state
      that a procedure is crucial means that withholding the procedure would be
      deleterious to the patient's health. Appropriateness and necessity ratings for
      six procedures were obtained using a modified Delphi panel process developed in
      earlier work. Panels were composed of practicing clinicians who were recognized
      leaders in their fields. The panels included both performers and nonperformers of
      the procedure under discussion. For most procedures and panelists, necessity was
      related to appropriateness, but was distinct from it. The proportion of
      indications for which the procedure was crucial varied in clinically consistent
      ways both among and within procedures. However, panelists did not achieve a
      consensus on necessity. Further research is suggested to refine the method to
      promote consensus and to validate further the ratings of necessity. In
      conclusion, necessity ratings can be used together with appropriateness ratings
      to address not only the overuse of procedures, but also to indicate limited
      access to care through underuse of procedures.

PMID- 8139301
TI  - A case-mix classification system for medical rehabilitation.
AB  - Dissatisfaction with Medicare's current system of paying for rehabilitation care
      has led to proposals for a rehabilitation prospective payment system, but first a
      classification system for rehabilitation patients must be created. Data for
      36,980 patients admitted to and discharged from 125 rehabilitation facilities
      between January 1, 1990, and April 19, 1991, were provided by the Uniform Data
      System for Medical Rehabilitation. Classification rules were formed using
      clinical judgment and a recursive partitioning algorithm. The Functional
      Independence Measure version of the Function Related Groups (FIM-FRGs) uses four
      predictor variables: diagnosis leading to disability, admission scores for motor
      and cognitive functional status subscales as measured by the Functional
      Independence Measure, and patient age. The system contains 53 FRGs and explains
      31.3% of the variance in the natural logarithm length of stay for patients in a
      validation sample. The FIM-FRG classification system is conceptually simple and
      stable when tested on a validation sample. The classification system contains a
      manageable number of groups, and may represent a solution to the problem of
      classifying medical rehabilitation patients for payment, facility planning, and
      research on the outcomes, quality, and cost of rehabilitation.

PMID- 8139302
TI  - Automated telephone reminders in tuberculosis care.
AB  - This study assessed the impact of automated telephone reminders in a population
      of 2,008 patients scheduled for appointments in a public health tuberculosis
      clinic. Overall, remainders increased appointment attendance from 52% to 62%.
      Reminders were more effective for some applications than others, but the
      effectiveness of reminders did not differ significantly across patient age, sex,
      or ethnicity. Counter to theoretical predictions, neither attribution of the
      reminder message to an authority nor a statement stressing the importance of the
      appointment significantly increased the effectiveness of the reminder above the
      level obtained without these enhancements.

PMID- 8139303
TI  - The ratio of observed-to-expected mortality as a quality of care indicator in non
      surgical VA patients.
AB  - This study attempts to validate the use of the observed-to-expected (O/E)
      mortality ratio as an indicator of quality of care. The primary objective is to
      determine whether medical records of 111 patients who died in Veterans Affairs
      (VA) hospitals with high overall ratios of observed-to-expected mortality rates
      show greater evidence that life might have been meaningfully prolonged with more
      expert care than the records of matched patients who died in VA hospitals with
      low O/E ratios. Patient matching criteria included: age, diagnosis responsible
      for length of stay, type of VA hospital, and the mortality probability predicted
      by logistic regression. Expert physicians blindly and independently reviewed
      pairs of medical records, assessing comparative care on a symmetrical, nine
      alternative visual analog scale. A slight shift in distribution toward better
      care in low-ratio hospitals was not statistically significant. Results of an
      additional analysis, not dependent on pairing, showed that preventability of
      death is more strongly related to physicians' estimates of mortality risk at
      admission, whether transferred from a nursing home, do-not-resuscitate status,
      and accuracy of discharge coding than to VA Medical Center O/E ratios.

PMID- 8139304
TI  - The accuracy of self-reported disability days.

PMID- 8139306
TI  - [The abandoned medical society].

PMID- 8139305
TI  - Misclassification of patients can affect group quality of care scores.

PMID- 8139307
TI  - [It's important that persons with language disabilities receive stimulative
      support].

PMID- 8139308
TI  - [Standardize nomenclature for changes of the squamous epithelium].

PMID- 8139309
TI  - [Beware of the surgery at small hospitals!...or?].

PMID- 8139310
TI  - [Computer tomography as a first choice examination of children with abdominal
      trauma].

PMID- 8139311
TI  - [Medical schools do not fulfill their obligations].

PMID- 8139312
TI  - [The society of patients with Meniere disease was founded].

PMID- 8139313
TI  - [Oophorectomy in connection with hysterectomy. Time for a reconsideration?].

PMID- 8139314
TI  - [Intravesical Bacillus Calmette-Guerin therapy. Effective immunotherapy against
      bladder cancer].

PMID- 8139315
TI  - [Lumbar myelography can be performed at the polyclinic. The atraumatic puncture
      needle is not better than the sharp needle].

PMID- 8139316
TI  - [Increased quality of life for patients with ostomies. A warning system for
      overfilled ostomy bags is valued].

PMID- 8139317
TI  - [Diagnosis-related groups. Insight gained at the department of gynecology and
      obstetrics in Angelholm].

PMID- 8139318
TI  - [Low back pain in pregnant women. There is much need for greater knowledge].

PMID- 8139319
TI  - [Depression after stroke. Antidepressive therapy enhances recovery].

PMID- 8139320
TI  - [Cutting down on "unnecessary" examinations. Increased risk of malpractice when
      an organ changes its position].

PMID- 8139321
TI  - [Occupational musculoskeletal diseases. Early rehabilitation is not unambiguously
      positive].

PMID- 8139322
TI  - [Jan Waldenstrom. The man behind macroglobulinemia].

PMID- 8139323
TI  - [n or more in clinical trials? Zelen's models for randomization].

PMID- 8139324
TI  - [Are private studies and training to be considered as continuing education?].

PMID- 8139325
TI  - [Can we prevent legalization of narcotics? Reliable alternatives in narcotics'
      policy are necessary].

PMID- 8139326
TI  - [How to persuade patients to change their life styles? There are successful
      strategies].

PMID- 8139327
TI  - [The physician in the movies ... The mad, the good, the dirty].

PMID- 8139328
TI  - [...and health on TV].

PMID- 8139329
TI  - [More about the extent and place of "heavy" surgery].

PMID- 8139330
TI  - [Reintroducing Swedish primary health care].

PMID- 8139331
TI  - [The value of early cancer diagnosis is no myth].

PMID- 8139332
TI  - [Thrombolytic therapy in myocardial infarction. Great regional differences].

PMID- 8139333
TI  - [Stroke units. Accumulated knowledge resources save both life and money].

PMID- 8139334
TI  - [Marfan syndrome. An old syndrome in a new light].

PMID- 8139335
TI  - [Increased quality of life after stroke. New therapeutic possibilities in
      depression].

PMID- 8139337
TI  - [Women's attitude to contraceptive agents].

PMID- 8139336
TI  - [Big changes of sexual habits among adolescents. Later start and increased use of
      condoms].

PMID- 8139338
TI  - [What does a 50 percent reduction of risk mean? Results from clinical trials are
      often misleading].

PMID- 8139339
TI  - [The man behind the syndrome: Friedrich Wegener. A famous pathologist behind a
      distinctive form of granulomatosis].

PMID- 8139340
TI  - [White-haired hermits as educational idealists].

PMID- 8139341
TI  - [Advertising discriminating against women!].

PMID- 8139342
TI  - [Aminoglycoside dosing--an updating].

PMID- 8139343
TI  - [Blood in feces. A screening method for early discovery of colorectal cancer].

PMID- 8139344
TI  - [Good diabetic care. Intensified insulin therapy is not always without risk-
      special knowledge is necessary].

PMID- 8139345
TI  - [Multiple pregnancy. An increasing obstetric and pediatric problem].

PMID- 8139346
TI  - [Erythromycin-resistant group A streptococci. High utilization is an explanation
      of increased occurrence].

PMID- 8139347
TI  - [Successful cataract surgery? Patients are satisfied in spite of vision
      problems].

PMID- 8139348
TI  - [Empathy and care in psychiatry. "Living" persons are the most appreciated by
      relatives].

PMID- 8139349
TI  - [Monoamine oxidase. Defect of MAO genes can cause behavioral disorders].

PMID- 8139350
TI  - [A national council for prevention of suicide was founded].

PMID- 8139351
TI  - [Global fight against suicide. 13 targets in the national program].

PMID- 8139352
TI  - [A center for research and prevention of suicide. Increased awareness of suicide
      is needed].

PMID- 8139353
TI  - [Clinical trials in new databases. Scandinavia in the Cochrane network].

PMID- 8139354
TI  - [n or less in a multicenter trial? Dimensions with good measures].

PMID- 8139355
TI  - [A new face of atherosclerosis. New discoveries about the role of nitric oxide
      result in complementary therapy methods].

PMID- 8139356
TI  - [By whom is homosexuality considered as a disease?].

PMID- 8139357
TI  - [Financing based on efficiency. 3-year experiences with a total cost
      responsibility system].

PMID- 8139358
TI  - [Efficiency based financing has many advantages. Optimal use of expensive
      resources].

PMID- 8139359
TI  - [Scientific fraud. Disagreement about definition of the concept].

PMID- 8139360
TI  - [Respiratory symptoms and pulmonary ventilatory function in greenhouse workers].
AB  - Respiratory symptoms and ventilatory capacity were studied in a group of 135
      women employed in greenhouses. In addition, a control group of 51 unexposed women
      were studied. Greenhouse workers had significantly higher prevalence of chronic
      cough, dyspnea, chest tightness and rhinitis (p < 0.01) than the controls.
      Smokers had significantly higher prevalence of chronic cough (p < 0.01) and
      rhinitis (p < 0.05) than nonsmokers. There was a high prevalence of acute
      symptoms during work shift. In greenhouse workers there was a statistically
      significant decrease of measured ventilatory capacity tests (except FVC) as
      compared to the predicted normal values, especially for FEF25. Smokers and
      nonsmokers had similar changes of ventilatory capacity as percentage of the
      predicted normals. Greenhouse workers exposed for more than 10 years had
      considerably lower FEF50 and FEF25 as percentage of the predicted values than
      those exposed for less than 10 years. Our data indicate that longer exposure in
      greenhouses may be associated with the development of acute and chronic
      respiratory impairment.

PMID- 8139361
TI  - [New diagnostic possibilities: urinary sediment digestion in an attempt to
      determine the etiology of urinary tract infections].
AB  - A selected sample of patients of juvenile age underwent this examination. They
      shared not only the common symptoms of inflammation, but also the incapability of
      isolating bacteria from the urine, or at least their insufficient isolation. A
      midstream urine specimen was collected and cultivated by Sanford's quantitative
      culture method. Following the staining of the urinary sediment by Gurr's method,
      the quantity of mucus and mucoid aggregates was estimated semiquantitatively. The
      rest of sediment was digested by lauryl sulphate in different concentrations. The
      aim of this research was to examine the influence of the depolymerization of
      mucus and other protein-like materials in urinary sediment on bacterial
      cultivation, as well as to find possible differences between the tested method
      and classical Sanford's urinary culture method. The difference in the number of
      cultivated bacterial species before and after digestion was significant (p <
      0.01). Different bacterial species were cultivated in 15 patients, the dominant
      species being Escherichia coli. It was cultivated 16 times, applying the method
      of digestion by lauryl sulphate in different concentrations, without previous
      cultivation by Sanford's method. All cultivational differences were noticed after
      the digestion of urinary sediment rich in mucus and mucoid elements.

PMID- 8139362
TI  - [Psychological status of Croatian refugees in Hungary].
AB  - This presentation addresses the capability of Croatian refugees from Baranja to
      acclimatize themselves in the Republic of Hungary. The authors assessed the
      mental health of 100 refugees through a psychiatric interview using a
      questionnaire, specifically designed for the purpose of this research. Their ages
      ranged from 10 to 82 years, average age 38 years. The assessment of mental health
      of the refugees was conducted 6 weeks following their placement in a camp (social
      institution) of a small town (Maria Jud) in Hungary. The authors found that
      refugees fled their homes and homeland in front of barbarous combined forces of
      local Serbs whom they identified as terrorists and Yugoslav Federal Army. Leaving
      homes and country was sudden and unexpected, but by their own will. The departure
      was accompanied by fear, anxiety, disbelief, despair, anger and rarely by panic
      behaviour. Fear for children's safety was on the first place, than fear from
      exposure to violent injury--torture and crippling, while threat for ones own life
      and life of relatives as well as loss of property were of milder intensity. Among
      the most dominant feelings refugees manifested during an interview were: home-
      and homeland sickness and uncertainty about the future. In 61% of the examinees,
      these feelings prevailed. Forty-two per cent of the subjects experienced
      emotional and psychosomatic disorders, primarily Beard's "neurasthenic syndrome".
      Only 5% of the refugees needed psychiatric help, mainly those who had psychic
      problems before they fled their homes. The authors conclude that Croats from
      Baranja who took refuge in Hungary had acclimatizational problems even 6 weeks
      after displacement, which were manifested as emotional and psychosomatic
      reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139363
TI  - [Relation between the size of the left-right shunt and pulmonary resistance in
      congenital heart defects].
AB  - Relation between pulmonary vascular resistance (PVR) and left-to-right (L-D)
      shunt has been statistically tested in 87 patients with congenital heart
      diseases. In all patients, PVR and L-D shunt were calculated from the
      catheterization test results. Among 87 patients, 45 (52%) were female and 42
      (48%) male children. The average age at the catheterization was 4.63 (min 6 mo,
      max 15 yr). Patients were divided into two groups with regard to the level of
      PVR. The first group consisted of patients with PVR higher than 160 dyn sec cm-5,
      and the second group with PVR lower than 160 dyn sec cm-5. The whole group was
      also divided according to VSD, and separate correlation was done for ASD with PVR
      below 160 dyn sec cm-5. A negative statistically significant correlation was
      observed between the height of PVR and size of L-D shunt among the entire group
      with PVR higher than 160 dyn sec cm-5, regardless of congenital heart disease (N
      = 29, r = -0.4676, P < 0.05). Also, a negative statistically significant
      correlation was found between PVR and L-D shunt in VSD, with PVR higher than 160
      dyn sec cm-5 (N = 17, r = -0.669, P < 0.05). Among patients with low PVR, there
      was no negative statistically significant correlation between PVR and L-D shunt,
      neither for the whole group (N = 58, r = 0.1174, P > 0.05), nor among the
      patients with VSD r = -0.0133, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139364
TI  - [Meteorologic effects and thrombocyte aggregation in patients with myocardial
      infarct living in the coastal region of central Dalmatia].
AB  - The circulating platelet aggregates were measured in 90 patients admitted to the
      Clinical Hospital Split because of myocardial infarction developed in the costal
      region of Middle Dalmatia. They were divided into three groups, each consisting
      of 30 patients affected by coronary incident developed during the three most
      characteristic weather types in the region: sirocco, bora and calm weather. All
      the patients have had elevated values of circulating thrombocyte aggregates, but
      the patients in the sirocco group exhibited significantly higher values (34.77%
      +/- 11.67%) than the patients in both bora (27.93% +/- 11.72%; p < 0.05) and the
      calm weather groups (23.5% +/- 10.62%; p < 0.01). In the control group of 10
      healthy examinees the values of circulating platelet aggregates were within
      normal range during all the three weather types (5.85% +/- 0.70%, 5.24 +/- 0.51%
      and 5.18 +/- 0.59%, in case of sirocco, bora and calm weather, respectively). The
      three groups were not significantly different regarding the values of creatinine
      kinase, which means that the infarct size was not the probable cause of the
      observed differences in platelet aggregability. Taking into account our previous
      finding of increased incidence of coronary events during sirocco, these results
      suggest that increased platelet aggregability is a contributing factor to the
      risk of myocardial infarction during such a weather.

PMID- 8139365
TI  - [Early predictors of outcome in children with head injuries].
AB  - In an attempt to determine whether the clinical data obtained by primary survey
      may be used as early outcome predictors in children who had sustained head
      trauma, children aged 0-14 with clinical diagnoses of coma, contusion, comotio,
      skull fracture or a combination of these diagnoses or who had been hospitalized
      for at least 3 days, between 1987 and 1990, were reviewed retrospectively. The
      outcome was defined by the clinical condition of children 6 months following head
      trauma using a Glasgow outcome scale (GOS), and was classified: good (good
      recovery and moderate disability) and poor (severe disability, persistent
      vegetative state, death). Of 70 children with trauma, 43 patients (61.4%) were
      separated by this method. The pupillary appearance and reactivity, Glasgow coma
      scale (GCS) and motor response graded by GCS were compared with the outcome. The
      analysis demonstrated that the early significant predictors of outcome of head
      trauma are the pupillary appearance and reactivity as well as Glasgow coma scale.
      Motor response graded by GCS did not achieve statistical significance (z = 1.5, P
      > 0.05) as a predictor of outcome. In this analysis, we have graded motor
      response according to the GCS criteria, thus it is not excluded that the use of
      different criteria could demonstrate the importance of motor response as an
      outcome predictor. In order to ascertain the significance of predictors in early
      outcome prognosis of head trauma, a relative risk for poor outcome was
      calculated. Our results showed that the significant predictors in descending
      order of preference are: pupillary reactivity, pupillary appearance and
      GCS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139366
TI  - [Aortico-left ventricular tunnel].
AB  - The boy was first admitted to the Department of Pediatric Cardiology at the age
      of 4 1/2 because of cardiac murmur diagnosed on the third day of life. A
      diastolic murmur of a grade 4/6, left ventricular hypertrophy as well as left
      aortal and ventricular dilatation were discovered. The findings showed a tendency
      of increase with time, but the patient had no symptoms. X-ray in the long axis
      view revealed a defect within the upper part of the interventricular septum
      immediately below the aorta, and dilated right coronary sinus. An invasive
      diagnostic method was undertaken, as well. The operative procedure was done with
      a total cardio-pulmonary bypass and hypothermia (29 degrees C). A tunnel from the
      anterior aortal wall through the outflow tract of the right ventricle to the left
      side of the heart was established intraoperatively. The defect was solved by a
      "sandwich" technique (two patch technique). Postoperative period was uneventful.
      A Doppler echocardiogram demonstrated the normal hemodynamic status of the
      patient without the left-to-right or right-to-left shunt and aortal
      insufficiency.

PMID- 8139368
TI  - [Quantitative analysis of nucleolar organizer regions in nevi and melanomas].
AB  - The results of a quantitative analysis of nucleolar organizer regions (NORs) in a
      group of 45 nevi and 45 melanoma are presented. Mean value of nucleolar organizer
      regions in nevi was 1.29 and the standard error 0.088. Melanoma had mean value of
      3.90 with a standard error of 1.542. Student's t test revealed a statistically
      significant difference between these two groups of benign and malignant
      melanocytic lesions of skin (P < 0.001), with regard to the number of NORs. In
      view of these results and those from the literature, the diagnostic value of the
      number of NORs in distinguishing benign from malignant melanocytic lesions of
      skin has been confirmed.

PMID- 8139367
TI  - [Summating potentials in the differential diagnosis of cochlear pathology].
AB  - Three groups of patients with Meniere's disease, sensorineural hearing loss
      caused by acoustic trauma, and healthy controls were examined by
      electrocochleography in order to establish the value of absolute summating
      potential (SP) amplitudes in the differential diagnosis of these entities. A
      statistically significant increase in absolute SP amplitudes was found in
      patients with Meniere's disease in comparison to patients with sensorineural
      hearing loss caused by acoustic trauma (p < 0.01). Besides that, there was also a
      statistically significant increase in absolute SP amplitude values in healthy
      persons, as compared to patients with sensorineural hearing loss caused by
      acoustic trauma (p < 0.05).

PMID- 8139369
TI  - [Renal metabolism of endogenous gastrin].
AB  - The kidney was thought to be the most important known site of the metabolism of
      gastrin. Specific mechanisms for gastrin catabolism in vivo have not been
      elucidated. Very little of the gastrin that is filtered by the kidney homogenates
      appears in the urine. The kidney tubule contains enzymatic activity that cleaves
      the C-terminal dipeptide amide from gastrin tetrapeptide, but it is not known if
      such an enzyme acts on the lager gastrin molecules. Removal of gastrin from the
      circulation is too rapid to be caused by any specific organ but rather must, be
      due to some nonspecific widespread metabolic process, probably existing in
      circulating serum. There are some lingering bits of evidence to suggest that
      although all capillary beds may extract gastrin equally, the renal bed may be
      first among equals.

PMID- 8139370
TI  - [Biologic role of Tamm-Horsfall glycoprotein].
AB  - The biological role of Tamm-Horsfall glycoprotein (THGP), a mucoprotein normally
      present in urine, is not quite clear as yet. The importance of THGP in urinary
      tract infections, genesis of urinary calculi and other diseases is discussed.

PMID- 8139371
TI  - [The first Croatian medical dictionary of Dr. Ivan Dezman (on the 125th
      anniversary of publication)].
AB  - The year 1868 marked the publication of the first "Dictionary of Medical Terms"
      in the Croatian language, the work of the physician and writer Ivan Dezman (1841
      1873) and one of the first professional dictionaries to appear in Croatia. In
      composing the dictionary Dezman made use of all the general Croatian language
      dictionaries which were available at the time, of the vernacular idioms as well
      as of the new words he coined himself. Although the dictionary was modest by
      volume, it comprised definitions for 3247 entries, its great value lied in the
      fact that is strongly influenced both the medical writing and future work on
      medical nomenclature.

PMID- 8139372
TI  - Triacylglycerol in biomembranes.
AB  - A better knowledge of the biochemical and biophysical properties of cell
      membranes has revealed fundamental concepts concerning the regulation of cell
      functions by intrinsic components of the lipid matrix. Membrane lipids exhibit
      high chemical heterogeneity, with hundreds of distinct chemical species; studies
      of structure-function relationships have unraveled new roles for an increasing
      number of these lipids as determinants of membrane structure, anchors for
      membrane-associated proteins or signalling agents. Recent observations have
      confirmed triacylglycerol (TG) as a quantitatively minor intrinsic membrane
      component which seems to play a specific role in important metabolic events such
      as cell stimulation or transformation and metastatic processes. The rapid
      turnover of the acyl chains into TG of cell membranes suggests an active
      metabolism. In the plasma membrane, TG appears to be implicated in the generation
      of transient non-bilayer domains suspected to be associated with specific
      cellular events. This paper summarizes the current information on TG metabolism
      and focuses on the potential role of this neutral lipid species on the structure
      and function of cell membranes.

PMID- 8139373
TI  - Deprenyl reduces serum prolactin concentrations in rats.
AB  - The effects of i.v. administration of deprenyl (2.5, 5, and 10.0 mg/Kg body wt),
      a monoamine oxidase inhibitor, on serum prolactin (PRL) concentrations were
      investigated in female Sprague-Dawley rats. In the rats treated with the highest
      dose (10 mg/Kg), serum PRL decreased by 48% (p < 0.05) within 30 min and remained
      depressed during a 240-min period. Serum PRL concentrations also decreased by 38%
      (p < 0.05) within 30 min in the rats treated with the 5 mg dose and remained low
      during the remainder of the period of observation. Serum PRL levels showed no
      change in the group treated with 2.5 mg of deprenyl/Kg BW, except at 240 min when
      it was 48% (p < 0.05) below the pretreatment levels. In the control group,
      injected with the vehicle (0.5 ml saline) no decreases in PRL levels were
      observed. The average serum PRL concentrations during the entire posttreatment
      period were 45% above the pretreatment levels in the control group, whereas they
      were 31% and 43% below the respective pretreatment levels in the 5 and 10 mg
      groups, respectively. In the 2.5 mg group, the average serum PRL levels during
      the posttreatment period were not different from those in the pretreatment
      period. It is concluded that deprenyl is a potent inhibitor of PRL release in the
      rat.

PMID- 8139374
TI  - Endotoxin elicits normal tryptophan and indolamine responses but impaired
      catecholamine and pituitary-adrenal responses in endotoxin-resistant mice.
AB  - The neurochemical and endocrine responses to endotoxin (LPS), Newcastle disease
      virus (NDV) and interleukin-1 (IL-1) administration were studied in endotoxin
      resistant mice. LPS has long been known to be a potent stimulator of the
      hypothalamo-pituitary-adrenocortical axis, but it also increases brain
      concentrations of the catabolites of norepinephrine (NE) and serotonin (5-HT), as
      well as free tryptophan. Mice of the endotoxin-resistant C3H/HeJ strain showed
      markedly reduced responses in plasma ACTH and corticosterone (CS) to
      intraperitoneal LPS compared to the control C3H/HeN strain. C3H/HeN mice
      displayed increases in the cerebral NE catabolite, MHPG, and the dopamine
      catabolite, DOPAC, but no such increases occurred in C3H/HeJ mice. However, the
      indolaminergic responses, increases of tryptophan and the serotonin catabolite, 5
      HIAA, were similar in the two strains. NDV administration induced responses very
      similar to those of LPS; increases in tryptophan and 5-HIAA, but impaired
      responses in catecholamines, ACTH and CS. IL-1 is known to be synthesized and
      secreted following LPS (and probably NDV) administration, and produces similar
      endocrine and neurochemical effects. In C3H/HeJ mice, IL-1 elicited normal
      increases in plasma ACTH and CS, as well as cerebral MHPG, 5-HIAA and tryptophan.
      Thus the deficits in C3H/HeJ mice do not reflect alterations in the ability of
      catecholamines and the HPA axis to respond to the immune system, but probably
      occur early in the sequence of reactions initiated by LPS and NDV. These results
      also suggest that LPS activates cerebral catecholamines and the HPA axis by
      similar or related mechanisms, whereas the indolaminergic responses apparently
      occur via a different mechanism.

PMID- 8139375
TI  - Growth of S49 wild type cells in 3 nM epinephrine increases cyclic AMP
      phosphodiesterase activity.
AB  - In this communication we report that intact cell measurements of cAMP decay have
      shown an increase averaging over 80% in the cAMP decay constant (kdy) in intact
      S49 WT cells following a 24 hour growth in 3 nM epinephrine (24 hr/3 nM
      epinephrine). A comparable percentage increase was seen in cell free PDE
      activities from cells similarly treated. The enhanced PDE activity and kdy were
      detectable after 6 hours of incubation with 3 nM epinephrine, and were maximal by
      24 hours of incubation. Lysate PDE activity returned to control levels within 24
      hours after the cells were transferred to epinephrine-free growth medium. The
      increased PDE activity present in S49 WT cells after 24 hr/3 nM epinephrine was
      the result of increased concentrations of the enzymes already present or the
      expression of very similar enzymes, rather than the expression of enzymes with
      markedly different characteristics. Firstly, the apparent Km values for the PDE's
      in lysates from control and 24 hr/3 nM epinephrine cells were both in the region
      of 1 microM. Secondly, PDE activities in lysates from 24 hr/control and 24 hr/3
      nM epinephrine S49 WT cells showed similar sensitivities to PDE inhibitors. There
      was support for the hypothesis that the increase in PDE activity in 24 hr/3 nM
      epinephrine S49 WT cells is dependent on the presence of cAPK. That is, although
      24 hr/3nM epinephrine caused a distinct homologous desensitization of adenylate
      cyclase in S49 kin cells, neither kdy nor lysate PDE activity were affected.
      Additionally, 24 hours incubation of S49 WT cells with 3 microM dibutyryl cAMP
      resulted in increased PDE activity. Finally, the stimulatory effect of 24 hr/3 nM
      epinephrine on PDE activity was inhibited in the presence of cycloheximide,
      suggesting the involvement of protein synthesis in the process. This study shows
      that prolonged treatment with very low concentrations of epinephrine results in
      an increase in PDE activity which had a significant effect on cAMP accumulation.
      The increases were quantified by intact cell and cell free measurements, with
      kinetic data which were consistent with the hypothesis that the increased PDE
      activity in 24 hr/3 nM epinephrine cells reflected an increase PDE synthesis
      which was dependent on activation of the cAPK.

PMID- 8139376
TI  - Ocular absorption and distribution of bendazac after topical administration to
      rabbits with different vehicles.
AB  - Ocular and systemic absorption of bendazac was investigated after topical
      administration to rabbits of 0.5% solutions of bendazac lysine in different
      polysaccharide vehicles. The results show that the drug is absorbed into the
      retina-choroid via an extracorneal, or sclero-conjunctival route; the iris and
      the ciliary body are presumably supplied via both the transcorneal and the
      extracorneal pathways. The extent of absorption via the extracorneal route is not
      related to vehicle viscosity but rather to the chemical features of vehicle. The
      transcorneal penetration appears to be hindered by the binding of the drug to
      corneal tissues.

PMID- 8139377
TI  - Levels of viral glycoprotein reflect enhanced effectiveness of combined drug
      treatments.
AB  - A chemosensitivity assay with small replicate Mm5mt/cl C3H mammary tumor cell
      cultures was developed to determine whether changes in viral antigen expression
      and release into culture fluids could be utilized as an in vitro measure of
      single and combined drug effect. The measurement of drug concentrations required
      for identical 50% reductions in viral antigen levels (ED50s) allowed the dosage
      dependence of the same drug to be compared alone and in combination drug
      treatments. The 52,000 MW viral envelope glycoprotein (gp52) of the mouse mammary
      tumor virus (MMTV) was measured in culture fluids of control and drug-treated
      cultures while cell density was simultaneously determined by cell staining and OD
      664 mu determination. While extracellular gp52 levels and cell density increased
      over 72 hours in control cultures, dose-dependent declines in both parameters
      provided dual measures of effect for combination CAF treatment [cyclophosphamide:
      doxorubicin (Adriamycin): 5-fluorouracil], combination CMF treatment
      [cyclophosphamide: methotrexate: 5-fluorouracil] and single component treatments
      of these combinations. Comparison of ED50s for gp52 reduction revealed that each
      drug's ED50 concentration was lower in combination treatment than it was in
      single treatment. In combined drug treatments, the ED50 of doxorubicin was
      lowered from 5.17 microM to 0.36 microM, that of 5-fluorouracil was lowered from
      0.69 microM to 0.22 microM and that of methotrexate was lowered from 15 nM to
      1.65 nM. Reductions of ED50 in combined drug treatments argued for drug
      synergisms in these combinations. When drug concentrations, rather than gp52
      reductions, were fixed at identical levels in single and combined treatments,
      additional declines in gp52 levels reflected the enhanced effects of CAF and CMF
      combinations over single drug treatments. When the anti-estrogen, tamoxifen, was
      added to CAF and CMF treatments, further declines in gp52 levels (below CAF and
      CMF levels) reflected the fact that these hormone-augmented treatments were more
      effective than either hormone or combination chemotherapy alone. These results
      indicate that decreases in extracellular levels of MMTV gp52 can be utilized in
      this in vitro assay as an alternative measure of chemotherapeutic effect for
      evaluating the synergistic or antagonistic nature of drug or hormone interactions
      and as a tool for in vitro optimization of combined drug effect.

PMID- 8139378
TI  - Impairment of male copulatory behavior in rhesus monkeys following acute
      administration of cocaine.
AB  - Although numerous studies in nonhuman primates have demonstrated an influence of
      cocaine on behavior, no studies have yet examined whether cocaine affects sexual
      behavior in nonhuman primates. The objective of the present study was to examine
      the acute effects of cocaine on male copulatory behavior of rhesus monkeys.
      Administration of cocaine produced dose-dependent effects on male copulatory
      behavior, with monkeys taking significantly longer to initiate copulation (mount
      latency) and achieve an ejaculation (ejaculation latency) after receiving 200-800
      micrograms/kg cocaine. Male copulatory behavior was not affected by cocaine at
      doses below 200 micrograms/kg. These results indicate that cocaine can acutely
      impair sexual behavior performance of male rhesus monkeys. Further study is
      needed to determine the possible long-term consequences of chronic cocaine
      administration on male sexual behavior.

PMID- 8139379
TI  - Antidepressants directly influence in situ binding of guanine nucleotide in
      synaptic membrane.
AB  - The present study examined the in vitro effects of antidepressants on functional
      photoaffinity labeling of GTP binding protein. Saturation binding studies were
      performed by incubating membranes with increasing concentrations of [32P]-AAGTP,
      followed by UV irradiation and SDS-PAGE. The specifically bound isotherms for
      each of the G proteins studied showed characteristics of a one site model.
      Scatchard analysis revealed increases in the Bmax and Kd of AAGTP binding for
      each of the G proteins (especially stimulatory G proteins) with the addition of
      antidepressants such as amitriptyline, clomipramine, desipramine and mianserin
      but not with monoamine oxidase inhibitor, antipsychotics and axiolytics. These
      results suggested that drugs having antidepressive properties may directly affect
      G protein, especially Gs protein.

PMID- 8139380
TI  - Scopolamine effects on the pressor response to thyrotropin-releasing hormone in
      humans.
AB  - Thyrotropin-releasing hormone (TRH) produces a marked pressor effect, which may
      be mediated by central cholinergic neurons, which in turn enhance sympathetic
      nervous system activity. In this study, 22 subjects (10 patients with Alzheimer's
      disease and 12 elderly controls) were administered IV scopolamine or placebo
      prior to administration of IV high-dose TRH (0.5 mg/kg). Systolic blood pressure
      was less on the day scopolamine was administered prior to TRH administration, as
      compared with placebo (F[1,20] = 6.12, p < 0.02). Results indicate that the
      pressor effect of TRH is attenuated by scopolamine, indicating a role of the
      cholinergic system in this response in humans.

PMID- 8139381
TI  - Clodronate (dichloromethylene bisphosphonate) inhibits LPS-stimulated IL-6 and
      TNF production by RAW 264 cells.
AB  - Effect of liposome-encapsulated and free clodronate on the IL-6 and TNF
      production by macrophages was studied using RAW 264 cell line as a macrophage
      model, and dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) for
      analysis of secreted cytokines. LPS-stimulated RAW 264 cells proved to produce
      notable amounts of these two cytokines, and DELFIA was sensitive and reliable
      method for analysis. Liposome-encapsulated clodronate inhibited the production of
      both cytokines, IL-6 being affected more than TNF, and the effect was mostly due
      to the drug itself, not to liposomal lipid. More than ten times higher
      concentration of free clodronate than liposomal clodronate was needed to inhibit
      cytokine production. This is the first report on the cytokine inhibitory property
      of clodronate, and the results support the idea of the use of liposomal
      clodronate as a macrophage suppressive agent in autoimmune diseases.

PMID- 8139382
TI  - Donor's and recipient's antigen presenting cells co-operatively enhance the allo
      reactive proliferation of peripheral blood lymphocytes.
AB  - Antigen-presenting cells (APC) play important roles in the allo-reactive
      proliferation of T cells in vitro and in the allo-graft rejection in vivo. This
      work was aimed at establishing whether a co-operation of any kind occurs between
      donor's and recipient's APC during allo-reactions, and whether certain cell
      surface molecules, such as beta 2-microglobulin (beta 2m) and human leucocyte
      antigens (HLA), are involved in such an interaction. The data herein reported
      show that the allo-reactive proliferation of peripheral blood lymphocytes (PBL)
      is markedly intensified by a positive co-operation between donor's and
      recipient's APC. Such a synergistic co-stimulatory action can be significantly
      hindered by a monoclonal antibody aimed against beta 2m while being not changed
      by monoclonal antibodies binding to either HLA-A-B-C or HLA-DR molecules. Hence,
      our preliminary results indicate that a positive interaction between donor's and
      recipient's APC may be of importance for allo-graft rejection.

PMID- 8139383
TI  - Ameliorative effect of dietary probucol on polychlorinated biphenyls-induced
      hypercholesterolemia and lipid peroxidation in the rat.
AB  - The hypocholesterolemic and antioxidant activities of probucol (PB) were examined
      in rats which were fed for 10 days with diets supplemented with or without 0.02%
      polychlorinated biphenyls (PCB). Dietary intake of PCB caused multiple effects on
      lipid metabolism, such as increased levels of both serum and HDL cholesterol, and
      increased TBA-reactive substances (TBARS), in hepatic subcellular fractions. PB
      1% in comparison with either control or alpha-tocopherol (Toc) 0.1%, reduced the
      serum cholesterol levels in normolipemic as well as in PCB-induced
      hypercholesterolemic rats. In addition, this drug ameliorated the elevated TBARS
      induced by PCB in the hepatic subcellular fractions, although less antioxidant
      activity was noted in rats fed PB than in those fed Toc. The microsomes isolated
      from various groups were incubated for 2h at 37 degrees C in the presence or the
      absence of ferrous iron in vitro; microsomes from the PB-fed rats were as much
      resistant against lipid peroxidation in ferrous-free incubation medium as were
      those from Toc-fed rats, while in the presence of ferrous iron there was a higher
      antioxidant effect on lipid peroxidation in the latter fraction than in the
      former. HPLC analyses showed that less PB than Toc was incorporated into the
      hepatic subcellular fractions, suggesting that the concentration of antioxidants
      in hepatic subcellular fractions determine the extent of lipid peroxidation in
      situ. These results suggest that the administration of PB is an effective
      approach for the treatment of both hypercholesterolemia and elevated lipid
      peroxidation while Toc ameliorates only an elevated lipid peroxidation.

PMID- 8139384
TI  - The release of oxytocin from spinal cord synaptosomes by high KCl depolarizing
      stimulus: a calcium dependent process.
AB  - Oxytocin (OT) release from synaptosomes isolated from the thoracic (T) and
      lumbosacral (LS) regions of the spinal cord was evoked by 56 mM potassium
      chloride (KCl). The release mechanism was shown to be a calcium dependent
      process. The ability of high KCl to evoke OT release from isolated nerve
      terminals in a calcium dependent manner provides additional support for the role
      of OT as a neurotransmitter in the spinal cord.

PMID- 8139385
TI  - Selective inhibition of major drug metabolizing cytochrome P450 isozymes in human
      liver microsomes by carbon monoxide.
AB  - The selectivity of carbon monoxide binding to specific human cytochrome P450
      isozymes was investigated by studying its inhibition of prototype reactions for 3
      major drug metabolizing P450s in liver microsomes: dextromethorphan O
      demethylation and (+)-bufuralol 1'-hydroxylation (P450DB1, CYP2D6), diclofenac 4'
      hydroxylation (P450TB, CYP2C subfamily), and midazolam 1'-hydroxylation (P450NF,
      CYP3A subfamily). The affinity of carbon monoxide is different for each P450
      isozyme. Warburg partition coefficients were 0.35, 1.1 and 3.9 microM for
      P450DB1, P450TB and P450NF, respectively. Differential inhibition by carbon
      monoxide may be a useful tool to identify specific human cytochrome P450 isozymes
      in the early screening of drug biotransformation catalysts. Further studies
      involving other P450 isozymes and substrates should extend our understanding of
      the phenomena and their implications.

PMID- 8139386
TI  - Redox state in liver mitochondria in acute copper sulfate poisoning.
AB  - A patient with acute copper sulfate poisoning was found to have maintained a
      relatively oxidized hepatic mitochondrial redox state in spite of his being in
      refractory shock. The mechanism underlying this unexpected clinical observation
      was investigated. The study involved the allocation of male Wistar rats into
      three groups; copper sulfate-treated (intraperitoneal injection), hemorrhagic
      shock, and control. Since the copper sulfate-treated rats developed severe
      hypovolemic shock, hypovolemia was induced in the hemorrhagic shock group to
      mimic the time course of blood pressure reduction in the copper sulfate-treated
      group. The control rats were injected intraperitoneally with a saline solution.
      The hepatic energy charge and the arterial ketone body ratio (AKBR), which
      reflects the hepatic mitochondrial redox state, of each group of rats was
      determined. The hepatic energy charge of the copper sulfate-treated rats
      decreased significantly, reflecting severe hypotension and copper sulfate-induced
      hepatic damage. This decrease was greater than that observed in the rats
      subjected to hemorrhagic shock. Despite the profound shock and the markedly
      decreased hepatic energy charge, the AKBR in copper sulfate-treated rats did not
      decrease compared with the control group, while the AKBR in rats with induced
      hemorrhagic shock did decrease significantly. These observations, together with
      in vitro studies, suggest that the relatively oxidized redox state of liver
      mitochondria in the copper sulfate-treated rats, notwithstanding the severe shock
      state of these animals, may be the result of direct oxidation of NADH by copper
      sulfate.

PMID- 8139387
TI  - (-)deprenyl increases activities of superoxide dismutase and catalase in certain
      brain regions in old male mice.
AB  - A subcutaneous continuous infusion of (-)deprenyl for 3 weeks in old C57BL male
      mice increased superoxide dismutase (SOD) and catalase (CAT) activities in s.
      nigra, striatum and cerebral cortex but not in hippocampus, cerebellum or liver.
      The doses of 0.5 and 1.0 mg/kg/day were most effective, while with a higher dose
      (2.0 mg/kg/day), deprenyl tended to lose its effect slightly and with a lower
      dose (0.25 mg/kg/day) deprenyl was clearly less effective. The results suggest
      that deprenyl can increase antioxidant enzyme activities in certain brain regions
      in mice as was previously demonstrated in rats of both sexes and different ages;
      this raises the possibility that deprenyl has this particular effect in animal
      species other than rats.

PMID- 8139388
TI  - Ursodeoxycholic acid reduces the systemic toxicity of 1,2-dichloro,4-nitrobenzene
      by stimulating hepatic glutathione S-transferase in mice.
AB  - Male C57BL/6 mice were fed with normal diet (ND) or diets containing 0.3 or 0.5%
      ursodeoxycholic acid (UDCA) for 3 weeks. Glutathione S-transferase (GST)
      activities in the liver cytosolic fraction of these animals toward 1,2-dichloro,4
      nitrobenzene (DCNB) as well as to 1-chloro,2,4-dinitrobenzene (CDNB) were
      significantly increased in a dose dependent manner in UDCA-treated groups
      compared with the control (ND-fed) animal group (one-way ANOVA). Reduced
      glutathione (GSH) levels tended to slightly decrease with UDCA diets but the
      difference did not attain a statistical significance (P > 0.05, one-way ANOVA).
      Twenty four hr survival rates after an oral challenge of 3.5 mg/kg of DCNB were
      significantly higher (P < 0.05, Chi-square test) in the two UDCA fed groups
      (10/10 for 0.5% group, 8/11 for 0.3% group) compared with the control group
      (3/11). Thus, UDCA appears to reduce the systemic toxicity of DCNB which is
      detoxified by the hepatic GST system. Although UDCA has been shown to exert
      hepatoprotective effects in experimental animals and humans in the past, to the
      best of our knowledge, the present study is the first report that UDCA reduces
      the systemic toxicity of a toxicant which is detoxified by the hepatic GST
      system. Although a direct proof is not available, it is most likely that the
      reduction of the systemic toxicity of DCNB was achieved by the increase in GST
      activity caused by UDCA feeding. This finding may open a new research field with
      regard to the unique biological properties of this bile salt in modulating
      hepatic detoxifying enzymes.

PMID- 8139389
TI  - Huperzine A as a pretreatment candidate drug against nerve agent toxicity.
AB  - Huperzine A (HUP) is a naturally-occurring, potent, reversible inhibitor of
      acetylcholinesterase (AChE) that crosses the blood-brain barrier. To examine its
      ability to protect against nerve agent poisoning, HUP was administered i.p. to
      mice, and the s.c. LD50 of soman was determined at various time intervals after
      pretreatment. Results were compared to those obtained for animals treated with
      physostigmine. A protective ratio of approximately 2 was maintained for at least
      6 hr after a single injection of HUP, without the need for any post-challenge
      drug therapy. By contrast, pretreatment with physostigmine increased the LD50 of
      soman by 1.4- to 1.5-fold for only up to 90 min. The long-lasting antidotal
      efficacy displayed by HUP correlated with the time course of the blood-AChE
      inhibition. The results suggest that the protection of animals by HUP from soman
      poisoning was achieved by temporarily sequestering the active site region of the
      physiologically important AChE.

PMID- 8139390
TI  - Gangliosides and atherosclerosis.
AB  - The ganglioside levels in atherosclerotic lesions of human aorta are considerably
      higher than those in unaffected areas of aorta, and atherosclerotic patients
      frequently have increased concentrations of serum gangliosides. The present
      review summarizes recent findings that suggest the possible involvement of aortic
      gangliosides in platelet activation and adhesion of platelets to the vessel wall.
      The effect of gangliosides on the structure of low density lipoproteins (LDL), on
      the interaction of LDL with macrophages and hepatic cells and on the LDL
      regulated biosynthesis of cholesterol is also discussed. In vitro experiments
      have demonstrated that a major ganglioside of the intima of atherosclerotic aorta
      induces rapid adhesion, aggregation and spreading of platelets. Moreover,
      gangliosides present in elevated amounts in the intercellular space of
      atherosclerotic aortic tissue modify the surface structure and stimulate
      aggregation of LDL. Ganglioside-modified LDL are readily recognized and taken up
      by macrophages, while preincubation of LDL with low concentrations of
      gangliosides inhibits LDL binding to hepatic cells. Thus, ganglioside enrichment
      of LDL is likely to interfere with LDL clearance via the hepatic cells. Thus,
      ganglioside enrichment of LDL is likely to interfere with LDL clearance via the
      hepatic LDL receptor, and to stimulate binding of LDL to the scavenger receptor
      of macrophages. It is postulated that high ganglioside levels in the aorta and
      serum may be an additional risk factor in atherosclerosis.

PMID- 8139391
TI  - Biphasic modulation of choline uptake and phosphatidylcholine biosynthesis by
      vasopressin in rat cardiac myocytes.
AB  - The effect of vasopressin on choline uptake and phosphatidylcholine biosynthesis
      in isolated rat heart myocytes was investigated. Myocytes were incubated with
      labelled choline in the presence of 0.05-1.0 microM vasopressin. Uptake of
      choline was enhanced (25%) by a low concentration (0.2 microM) of vasopressin,
      but was attenuated (19%) by a higher vasopressin concentration (1.0 microM). The
      biosynthesis of phosphatidylcholine was also affected by vasopressin in a
      biphasic manner. At low concentrations of vasopressin, a general increase in
      cytosine triphosphate:phosphocholine cytidylyltransferase activity was observed
      that caused an enhanced conversion of phosphocholine to phosphatidylcholine via
      the cytidine diphosphocholine pathway. At high vasopressin concentrations, a
      decrease in the activity of cytidylyltransferase was detected, which was caused
      by the translocation of the enzyme from the microsomal fraction to the cytosolic
      fraction. The decrease in enzyme activity coincides with a reduction in the
      conversion of labelled phosphocholine to phosphatidylcholine. In view of the fact
      that phospholipid biosynthesis in rat hepatocytes is inhibited by vasopressin at
      all concentrations, the biphasic modulation of phosphatidylcholine biosynthesis
      in rat heart myocytes illustrates the diverse effects of this hormone in
      different mammalian tissues.

PMID- 8139392
TI  - Interaction of dietary fatty acids and cyclosporine A in the borderline
      hypertensive rat: tissue fatty acids.
AB  - In this study we examined (i) the effects of cyclosporine A (CS) on tissue lipid
      composition and (ii) the effect of changes in dietary n-6 fatty acids on tissue
      responses to CS. Fatty acid composition of liver, kidney, heart and brain were
      determined after 4 wk of treatment with CS (10 mg/kg.d p.o.) in male borderline
      hypertensive rats (BHR, n = 4/group), whose diet was supplemented with either
      safflower oil or evening primrose oil (EPO). Phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylserine/phosphatidylinositol, triglyceride
      and cholesteryl ester fatty acids were measured in kidney, heart, brain and
      liver. The same parameters were also measured in safflower-fed BHR (n = 4)
      receiving placebo. The effects of CS on liver microsomal delta 9, delta 6 and
      delta 5 desaturases in vitro were also followed. CS affected the fatty acid
      composition of all tissues examined, with the greatest changes seen in the renal
      phosphatidylcholine and phosphatidylserine/phosphatidylinositol fractions. All CS
      induced changes that occurred in the liver, brain and renal fatty acids were
      reversed by EPO. CS elevated delta 9 desaturase but had no effect on delta 6 and
      delta 5 desaturase. In light of (i) the observation that EPO normalizes renal
      function and blood pressure in CS-treated BHR, and (ii) the importance of the
      kidney in blood pressure regulation, the data suggest that the beneficial effects
      of EPO on CS toxicity may involve changes in renal phospholipid fatty acid
      profiles.

PMID- 8139393
TI  - Effects of dietary protein and cholesterol on phosphatidylcholine and
      phosphatidylethanolamine molecular species in mouse liver.
AB  - The present study examined the effects of two atherogenic factors, animal protein
      and cholesterol, on the distribution of fatty acids and the molecular species of
      major liver phospholipids in mice. Weanling mice were fed a semisynthetic diet
      supplemented with either casein or soy protein (20%, w/w) in the presence or
      absence of 0.5% cholesterol for 4 wk. Results from mouse liver showed that animal
      protein and, more so, dietary cholesterol modified the fatty acid profiles of the
      phospholipids. Animal protein had no significant effect on the concentration of
      lipids, but it altered the relative distribution and fatty acid profiles of the
      phospholipids, phosphatidylcholine and phosphatidylethanolamine. Dietary
      cholesterol, on the other hand, significantly increased the concentration of
      liver lipids, but it did not alter the relative distribution of
      phosphatidylcholine and phosphatidylethanolamine. In cholesterol-fed mice, the
      proportions of molecular species containing 18:2n-6 were increased, whereas those
      containing 20:4n-6 were decreased, indicating that dietary cholesterol suppressed
      linoleic acid metabolism. Since cholesterol feeding selectively decreased the
      ratio of 18:0/20:4n-6 in phosphatidylcholine, whereas it increased the 18:0/18:2n
      6 ratio in phosphatidylethanolamine, this finding suggests that dietary
      cholesterol may affect the incorporation of fatty acids but not the rate of
      synthesis of phosphatidylcholine and phosphatidylethanolamine.

PMID- 8139394
TI  - Effect of dietary fish oil on blood levels of free fatty acids, ketone bodies and
      triacylglycerol in humans.
AB  - Although the reduction of serum triacylglycerol concentrations by dietary fish
      oil is a well-known effect, the exact mechanism of this effect has not been
      previously studied in human subjects. Therefore, the aim of this study was (i) to
      examine the effect of short-term fish oil supplementation on blood concentrations
      of ketone bodies, free fatty acids and triacylglycerol in healthy humans and (ii)
      to verify whether the observed relationships between these variables would be
      consistent with reduced lipolysis and/or enhanced hepatic fatty acid oxidation
      after fish oil supplementation. Twenty subjects (21-23 years, normal liver
      function tests) were randomly divided into two groups to supplement their usual
      diet with either 30 g/d of fish oil (n = 11) or olive oil (n = 9). Venous blood
      samples were drawn after an overnight fast, before and after 1, 3 and 7 d of fish
      oil/olive oil supplementation. Blood concentrations of triacylglycerol and free
      fatty acids decreased consistently after fish oil supplementation; the reduction
      was already significant after one day of fish oil (P < 0.001 for triacylglycerol
      and P = 0.01 for free fatty acids). In contrast, neither of these blood values
      changed after olive oil supplementation (P > 0.10). No significant changes in
      glucose, insulin or ketone body levels were observed in either group after
      supplementation. After fish oil, but not after olive oil supplementation, the
      ratio of blood ketone body levels to free fatty acid levels increased
      significantly (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139395
TI  - Lipid peroxidation and antioxidant status is affected by different vitamin E
      levels when feeding fish oil.
AB  - The protective role of vitamin E and changes in the status of several
      physiological antioxidants after feeding rats a fish oil diet were investigated.
      Six-week-old male Sprague-Dawley rats were divided into four groups and fed
      experimental diets for 8 wk. Three fish oil (FO) groups were fed a menhaden fish
      oil and soybean oil (SO) (9:1) mixture as 10% (w/w) of the diet. These groups
      were provided with < or = 3, 45 or 209 IU of vitamin E/kg diet. One SO group was
      used as control and was fed < or = 45 IU of vitamin E/kg diet. Plasma vitamin E
      levels, when expressed as vitamin E per mL plasma, were extremely low in the
      group fed FO and < or = 3 IU of vitamin E, and were lower in the groups fed FO
      than in the group fed SO. However, plasma vitamin E levels when expressed per mg
      plasma lipid were higher in the FO groups provided with < or = 45 and 209 IU of
      vitamin E than in the SO group. Compared with the SO group, plasma levels of
      thiobarbituric acid reactive substances (TBARS), when expressed per mg lipid,
      were higher in the three FO groups, plasma retinol levels were lower in the FO
      groups provided with < or = 3 and 45 IU of vitamin E, and ascorbic acid levels
      were lower only in the FO group provided with < or = 3 IU of vitamin E. Blood
      glutathione (GSH) levels were lower in all three FO groups than in the SO
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139397
TI  - Abnormal plasma lipids of patients with Retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a hereditary retinal degeneration of unknown
      etiology, resulting in progressive night blindness, loss of peripheral vision,
      abnormal retinal pigmentation and reduced electroretinographic response.
      Docosahexaenoic acid (22:6 omega 3) is found in high concentration in the rod
      outer segment membranes of the retina. Previous reports of low 22:6 omega 3 in
      blood lipids or phospholipids in RP patients prompted us to evaluate the complete
      fatty acid (FA) profiles of plasma phospholipids (PL), cholesteryl esters,
      triglycerides (TG) and nonesterified fatty acids (NEFA) in ten patients with RP.
      In the PL fraction, we found significantly depressed levels of 22:6 omega 3, 22:5
      omega 3, total omega 3, 22:5 omega 6, 22:4 omega 6 and total omega 6
      polyunsaturated FA (PUFA), and elevated total saturated acids. Plasma TG showed
      normal levels of PUFA, normal total saturated FA and total monounsaturated FA.
      The NEFA fraction showed significant elevation in total saturated FA with
      depressed total omega 6 PUFA. Evidence is accumulating mulating that RP is
      associated with abnormal PUFA and lipid metabolism.

PMID- 8139396
TI  - Effect of maternal dietary arachidonic or linoleic acid on rat pup fatty acid
      profiles.
AB  - Rapidly growing neonatal mammals accrete relatively large quantities of long
      chain (> or = C20) polyunsaturated fatty acids (LCP) in membrane phospholipids.
      We have examined accumulation of omega 6 LCP in suckling neonatal rat pups during
      the first 14 d of life when their dams received essential fatty acids in the form
      of triglycerides containing linoleic acid or arachidonic acid. Dietary levels of
      these fatty acids were either 1 or 5% of total dietary fatty acids. The fatty
      acid profile of pup stomach contents (composed solely of the dams' milk) and
      plasma lipids, as well as liver and brain phospholipids, were determined. Stomach
      linoleic and arachidonic acid levels reflected the diet of the dams. Pup plasma
      and liver arachidonic acid levels increased progressively from the group
      receiving 1% linoleic acid to 5% linoleic acid and from 1% arachidonic acid to 5%
      arachidonic acid. Interestingly, brain phosphatidylethanolamine and
      phosphatidylcholine arachidonic acid levels were more stable than plasma or liver
      levels. These results suggest that the brain may be capable of either selective
      transport of omega 6 LCP or chain elongation/desaturation of linoleic acid. These
      data indicate that care must be exercised when adding LCP to infant formula since
      widely divergent accretion rates of arachidonic acid may occur in various
      tissues.

PMID- 8139398
TI  - Effects of high corn oil diet on preneoplastic murine colons: prostanoid
      production and lipid composition.
AB  - In the present study, the effect of normal (5% by wt) and high (23.5% by wt) corn
      oil diets on prostanoid production and on the lipid composition of preneoplastic
      colonic epithelium was investigated. CF1 mice (female, 3-4-weeks-old) were fed a
      normal corn oil diet ad libitum and were treated with the colon carcinogen 1,2
      dimethylhydrazine (DMH, 20 mg/kg/wk) or saline (control) for 24 wk. At this
      stage, all animals received the AIN-76 diet (normal corn oil) ad libitum.
      Following the last injection, half of the animals from each treatment group were
      randomly allocated to a high corn oil diet for 5 to 10 wk, whereas the remaining
      animals continued on the normal corn oil diet. After 5 wk of feeding, the colonic
      mucosa of carcinogen-treated animals had a higher level of bicyclic prostaglandin
      E2 (PGE2) than had the animals in the control groups; prostanoid synthesis in the
      colonic mucosa of control animals was unaffected by the high corn oil diet.
      Preneoplastic colonic mucosa of animals fed the high corn oil diet had a
      significantly higher level of PGE2 than corresponding control colonic mucosa. The
      6-keto-prostaglandin F1 alpha/thromboxane B2 ratio was significantly lower in the
      DMH-treated groups than in the control groups, and was unaffected by dietary
      treatments. After 10 wk of feeding a particular diet, the differences in the
      fatty acid composition between the control and DMH-treated groups were minor. Our
      findings demonstrate that the preneoplastic colonic epithelium differs from that
      of normal epithelium with respect to prostanoid synthesis.

PMID- 8139399
TI  - Regulation of rat liver microsomal cholesterol ester hydrolase by reversible
      phosphorylation.
AB  - The regulation of neutral cholesterol ester hydrolase activity by changes in its
      phosphorylation state was studied in rat liver microsomes. Treatment with cAMP
      dependent protein kinase resulted in increased enzyme activity, which was further
      enhanced by the addition of cAMP and MgATP. Consistent activations were also
      achieved with MgCl2 and MgATP, the magnesium effect being abolished by
      ethylenediaminetetraacetic acid and adenosine triphosphate. Cholesterol ester
      hydrolase was activated twofold by free calcium and Ca2+/calmodulin; this latter
      effect was blocked by the chelator ethylene-glycol-bis(beta-aminoethyl
      ether)N,N,N',N'-tetraacetic acid and the calmodulin antagonist trifluoperazine.
      The phosphatase inhibitors pyrophosphate and glycerophosphate led to marked and
      dose-dependent increases in esterase activity, whereas okadaic acid elicited no
      effect. Furthermore, pyrophosphate and okadaic acid did not change the increases
      in enzyme activity promoted by Ca2+, Ca2+/calmodulin, Mg2+ and MgATP. Cholesterol
      ester hydrolase was inactivated in a concentration-dependent manner by
      nonspecific alkaline phosphatases. In cAMP-dependent protein kinase/cAMP- or
      Ca2+/calmodulin-activated microsomes, a time-dependent loss of activation in
      cholesteryl oleate hydrolysis was caused by alkaline phosphatase. These findings
      suggest that microsomal cholesterol ester hydrolase is activated through cAMP and
      Ca2+/calmodulin phosphorylation, whereas enzyme deactivation is dependent on
      phosphatase action.

PMID- 8139400
TI  - An improved method for the measurement of malondialdehyde in biological samples.
AB  - An improved method was developed for measuring malondialdehyde (MDA) as its
      thiobarbituric acid (TBA) complex. Samples were initially incubated with 1%
      potassium iodide and 0.1% butylated hydroxytoluene at 50 degrees C for 20 min,
      and then with 0.4% TBA at 60 degrees C for 60 min. The MDA-TBA complex formed was
      extracted with isobutyl alcohol and measured by high-performance liquid
      chromatography with fluorescence detection. The improved method allows for a more
      specific determination of MDA present in biological samples.

PMID- 8139402
TI  - Twelve tips for using role-plays in clinical teaching.

PMID- 8139401
TI  - Molecular species of choline and ethanolamine glycerophospholipids in rat brain
      myelin during development.
AB  - The composition of the molecular species of various phospholipid subclasses was
      examined in myelin isolated from brain of 15-, 21- and 90-day-old rats. The
      molecular species of diacylglycerophosphocholine (PtdCho),
      diacylglycerophosphoethanolamine (PtdEtn) and plasmenyl-ethanolamine (PlsEtn)
      were quantified by high-performance liquid chromatography (HPLC) after
      phospholipase C treatment and dinitrobenzoyl derivatization. In rat brain myelin,
      each phospholipid subclass showed a specific pattern of molecular species that
      changed during development. PtdCho contained large amounts of
      saturated/monounsaturated and disaturated species and low amounts of
      saturated/polyunsaturated species. During brain development, the levels of
      saturated/monounsaturated molecular species increased whereas those of the
      disaturated and saturated/polyunsaturated species decreased. PtdEtn were
      characterized by their low levels of disaturated species and a high content of
      saturated/monounsaturated and saturated/polyunsaturated species, of which those
      containing fatty acids of the n-3 series decreased, whereas those containing
      fatty acids of the n-6 series did not change during brain development. The levels
      of saturated/monounsaturated species increased in PtdEtn. No disaturated
      molecular species could be detected in PlsEtn. This alkenylacyl subclass
      contained large amounts of saturated/polyunsaturated, saturated/monounsaturated
      and dimonounsaturated molecular species. During development, the levels of
      saturated/polyunsaturated molecular species decreased while those of the two
      others increased. The data indicated that myelin sheaths undergo phospholipid
      changes during brain development and maturation.

PMID- 8139403
TI  - Introducing physiotherapy students to the idea of 'reflective practice'.
AB  - Absence of precise definitions of such terms as 'reflection' and 'reflective
      practice' may result in reluctance to explore methods of introducing the
      underlying ideas to students. In this paper some views on meaning are considered
      and reflection is introduced to a group of physiotherapy students as a tool in
      active learning. Transcripts of the students' reflections during a pre-clinical
      and a clinical experimental learning exercise are presented and discussed.

PMID- 8139404
TI  - Teaching medical diagnosis: a rule-based approach.
AB  - This paper discusses the design of a diagnostic process simulator which teaches
      medical students to think clinically. This was possible to achieve due to the
      application of a rule-based approach to represent diagnosis and treatments.
      Whilst using the simulator, as a result of the student's incorrect and correct
      decisions, the clinical situation changes accordingly. New diagnostic options
      result in the ability to choose further clinical and laboratory tests. The
      simulator is being implemented on Sun workstations and Macintosh computers using
      Prolog programming language.

PMID- 8139405
TI  - The effect of formal instruction in ophthalmoscopy on medical student
      performance.
AB  - Ophthalmoscopy is an essential part of a complete clinical examination of a
      patient. However specific formal instruction in fundoscopy is rarely given to
      medical students. We decided to determine the value of explicit teaching of
      ophthalmoscopy and devised and validated a rating scale for assessing performance
      which was used to evaluate 29 first year clinical medical student volunteers at
      St. Bartholomew's Hospital Medical College, before and after formal instruction
      in fundoscopy. The competence of this group at ophthalmoscopy was then compared
      to the rest of their year (109 medical students) during the objective structured
      clinical end-of-year examination. Students formally instructed in ophthalmoscopy
      showed an improved score after instruction (from 53% to 77%). They also performed
      better at fundoscopy than the rest of their year (mean average score 64%), when
      tested 2 months later, suggesting persistence of the training effect. However as
      a group they performed no better than their peers at clinical skills other than
      ophthalmoscopy. We suggest that as fundoscopy is such an important clinical
      skill, medical students should be given specific teaching, preferably in their
      ophthalmology firm attachment, as we have shown that it results in a persistent
      improvement in performance.

PMID- 8139406
TI  - Formative evaluation of a multimedia CAL program in an ophthalmology clerkship.
AB  - The use of computer-aided learning (CAL) in medical education has grown
      considerably in recent years. CAL has a number of attractive educational
      features, and computer simulations have been shown to improve learning in health
      professions education. This paper describes the formative evaluation of a
      multimedia CAL simulation used in a third year ophthalmology clerkship. The CAL
      program combines the use of a Macintosh computer with a mannequin head, housing
      two motor driven camera diaphragms which simulate pupil response. This allows
      students to practice the "swinging flashlight test", an important clinical exam
      commonly used to detect visual dysfunction. Five questions are addressed in this
      study and the formative evaluation process is described. The highly positive
      results are then presented, with suggestions given for improvement followed by
      implications for future development.

PMID- 8139407
TI  - Elementary anatomy for the future general practitioner: the arteries.
AB  - In all countries of the world the amount of time allotted to teaching anatomy has
      been drastically reduced. This study is intended to be a contribution to
      defining, against such a background, a basic stock of macroscopic anatomy that
      should be required from every medical student, whatever branch of the profession
      he may eventually engage in. More advanced knowledge, specific to a particular
      specialty, will be integrated into the resident's curriculum. In this way free
      time will be made available so that the gifted student can be given an effective
      introduction into contemporary morphological research. In the chapter on the
      arteries, general medical relevance is granted to only 13.2% of the vessels
      mentioned in the International Nomenclature. Marked reduction in the amount of
      teaching of macroscopic anatomy seems therefore to be possible, without
      surrendering a full, clinically-orientated education.

PMID- 8139408
TI  - Preliminary evaluation of a new curriculum--incorporation of problem based
      learning (PBL) into the traditional format.
AB  - An account of the establishment of a Problem Based Learning (PBL) curriculum at
      the Eric Williams Medical Science Complex Republic of Trinidad and Tobago
      provides the forum for a critical analysis of this process and for dialogue with
      current relevant literature on similar attempts elsewhere. Initial resistance to
      change and the assessment of the new system is discussed in the light of the fact
      that this is the first Caribbean territory to adopt Problem Based Learning as the
      major instrument to be employed in tertiary level medical education. The analysis
      uncovers a model of practitioner/researcher which provides a useful conceptual
      and operational framework for the articulation of the role of those engaged in
      effecting and studying the management of change.

PMID- 8139409
TI  - The use of objective structured clinical examination (OSCE) for detecting and
      correcting teaching-learning errors in physical examination.
AB  - The innovative use of Objective Structured Clinical Examination (OSCE) to detect
      and correct teaching-learning (T-L) errors in clinical skills is described. The
      group performance errors could be classified as Type I (faulty performance or
      omission of a step), Type II (failure to recognize or correctly interpret a
      clinical sign) or combined (Type I & II) errors. Type I errors were due to
      ineffective or absent T-L experiences. Type II errors were due to poor concept
      attainment or inability to discriminate between the differences in a clinical
      sign. Clinical demonstration during feedback was effective in eliminating Type I
      errors. Correcting Type II errors of the group needed more time and effort and
      was only partially effective.

PMID- 8139410
TI  - Clinical evaluation: physiotherapists' ranking of competencies.
AB  - The competencies to be assessed as part of the process of clinical evaluation of
      students need to be determined. This paper describes a method establishing the
      emphasis or weights assigned to each area of competency. Clinicians and clinical
      educators were asked to rate a number of dummy student evaluation forms and the
      individual competencies on each form. Category weights were derived and the
      magnitude of these weights were used to rank the categories. The derived ranks
      were compared to the rater's overt ranking of the categories. The weightings are
      compared to those reported in other studies which examine the value placed on
      clinical competencies by clinicians.

PMID- 8139411
TI  - A new way to assess practical physiotherapy skills.
AB  - This paper describes an innovative method of assessing the practical skills of
      physiotherapy students. The practice of identifying quality in Quality Circles
      and using Standards as guidelines is applied to the teaching of pre-clinical
      skills. The Standards, as identified by the students are then used as marking
      criteria in an assessment which utilises the principles of self and peer review.
      The assessment appears to encourage evaluative skills early in the undergraduate
      programme and bridges the gap between learning skills merely at a technical level
      and clinical work.

PMID- 8139412
TI  - [Effect of extent of coronary artery occlusion on the hydrodynamics of
      aortocoronary shunts of various geometries].

PMID- 8139413
TI  - [Lighting of biological objects during their visual recording by super thin rigid
      endoscopes].
AB  - The paper deals with the effects of illumination intensity levels on perception
      conformality and colour saturation in the image of a biological object. Reveals
      the impact of the optical parameters of an endoscope, the parameters
      characterizing the biological object and its illumination intensity on the
      resolution of the optic system of observer's eyes--an endoscope. The biological
      object illumination intensity range recommended in its visual recording by using
      rigid endoscopes is defined.

PMID- 8139414
TI  - [A unified series of microtomes for biology and medicine on the basis of
      rotational microtome].
AB  - A block-module constructor for the assembly of rotation microtomes is described.
      The microtomes are used for cutting fixed and native tissues. The basic rotation
      microtome is the main element of the microtome constructor. A set of changeable
      modules enables one to assemble microtomes on the basis of the basic rotation
      microtome for cutting fixed embedded tissue, 5-20 microns thick, fixed
      nonembedded tissue, 75-300 microns thick, native tissue, 150-600 microns thick,
      as well as a microtome-vibratome (the thickness of sections is 50-200 microns). A
      universal microtome combining all the mentioned-microtomes may be designed. The
      problems of fixed and native tissue microtomy are discussed in the paper.

PMID- 8139415
TI  - [Training of medical physicists in Russia].
AB  - The paper shows the role and place of medical physicists in modern society, gives
      an analysis and recommendations on training such specialists in our country and
      abroad.

PMID- 8139416
TI  - [Specific problems in the development of pulse oximeters].

PMID- 8139417
TI  - [Computerized control with radiodiagnostic equipment in bronchopulmonary
      investigations].
AB  - The authors propose a procedure and equipment for control by using a rotation
      table of a PYM-20M X-ray system with an image intensifier. A 4 x 4-cm beam field
      is used. The procedure makes it possible to lower X-ray loads in patients by 10
      15 times, to calculate the absorbed integrated radiation dose, to enhance the
      quality of plane films, to draw up a protocol of studies. This increases the
      accuracy of X-ray anatomic instrument position. The apparatus can be remotely
      controlled.

PMID- 8139418
TI  - [Apparatus for the control of physiologic status of the patients during
      experimental medical studies in the hypoxic chamber].

PMID- 8139419
TI  - [Automatic measurement of parameters in cardiointervalography].

PMID- 8139420
TI  - [A device for photoprocessing of radiologic films].

PMID- 8139421
TI  - [Radiologic dose indicator (INDOR-C)].

PMID- 8139422
TI  - [Linear accelerator of decompression for indirect blood pressure measurement].
AB  - The paper provides the author's decompression linearizer of indirect blood
      pressure measuring device which is intended for automatic maintenance of constant
      decreases of air pressure in the cuff and represents a controlled pneumo
      resistance whose values are automatically changed under the action of pressure
      and air consumption in the meter cuff. The use of the linearizer enhances the
      accuracy of measurements and their repeatability and significantly reduces the
      operating time of blood pressure measurements both under routine conditions when
      blood pressure is measured by the Korotkov method and particularly in the auto
      mode.

PMID- 8139423
TI  - [Improved modification of "Vitreotome" tip for intraocular surgeries].
AB  - An improved designed of the tip of the ABO-I vitreotome manufactured at the
      Russian plants has been proposed. The modification consists in that the tip
      combines irrigation and aspiration systems, as well as the rate of irrigative
      solution infusion can be controlled. The clinical trials of the improved
      modification of the vitreotome tip have indicated that it is easy-to-use and
      minimizes surgical and hydraulic injuries to the ocular tunica and structures.

PMID- 8139425
TI  - [A set of protective devices used in teeth preparation].

PMID- 8139424
TI  - [An instrument for ophthalmologic surgical measurements].
AB  - Intensively improving the techniques of eye microsurgery presents higher
      requirements for the accuracy of intraoperative measurements of the eyeball and
      accessory ocular apparatus. A unit has been proposed for intraoperative
      ophthalmosurgical measurements, which will increase measurement accuracy up to
      0.1 mm, which is beyond the reach of the conventional units.

PMID- 8139426
TI  - [A set of instruments for aortocoronary shunting].

PMID- 8139427
TI  - [A set of microinstruments for orbital surgeries].

PMID- 8139428
TI  - [A set of instruments for osteoplastic surgeries].

PMID- 8139429
TI  - [A set of instruments for microsurgery of bile ducts].
AB  - A set of instruments for bile duct microsurgery is convenient to work in surgical
      institutions, which are specially and widely engaged in surgical interventions
      into the bile duct and vessels. It is is quite essential for reconstructive
      reoperations on the bile and pancreatic ducts.

PMID- 8139430
TI  - [A universal set of instruments for microneurosurgery].
AB  - The proposed set meets the requirements of microsurgical operations on the
      central and peripheral nervous system, cerebral vessels and contains the
      requisite minimum of instruments. The form and size of the instruments are easy
      to-use, which has been confirmed during numerous operations.

PMID- 8139431
TI  - [Radiologic medical vacuum universal cassette].

PMID- 8139432
TI  - [Approach to the development of radiologic data base].

PMID- 8139433
TI  - [Chronic Chagas cardiomyopathy: methods for identifying groups at risk and/or
      risk behaviors].
AB  - Chagas' disease is still in 1992 a true problem of Public Health in several
      countries of South America. Almost 1/3 of the infested patients will develop a
      heart complications particularly lethal: the Chagas' chronic cardiopathy. The
      existing drugs do not cope with this Public Health problem. Such a lack of
      therapy enlarged because of the success of vectors control, has based the main
      strategies for the years to come, i.e. eradication of the insects of Triatoma.
      infestans group. So, there is a great risk to look upon the patients already
      infested and threatened with acute heart complication. Many factors have an
      influence on the occurrence of such a complication. Therefore, identification of
      groups or behaviours at risk should lead to an adapted strategy to take care of
      the patients already infested by Trypanosoma Cruzi. The authors propose a
      methodology which taking into consideration all "may be risk factors", eases a
      graded conceptual model. This model will be certainly useful in identifying some
      pertinent parameters, in elaborating or accepting some data collection
      technology, in data analysis, as well as in setting up some operational research
      projects.

PMID- 8139434
TI  - [Developmental aspects of a bilharziasis caused by Schistosoma mansoni].
AB  - The diagnosis of meningo-radiculitis of unknown etiology was posed on a adult
      Caucasian male patient, based on clinical and biological symptoms offered since
      1991, February (CSF: lymphocytic with hyperproteinosis). The patient had stayed
      in different bilharzia endemic zones. Confronted with a lack of improvement, even
      an aggravation and facing an appearance of a pyramidal symptom of the limbs,
      mostly at left, with ataxia preventing walking, one admitted the patient several
      times to do biological and radiological tests. They confirmed the troubles at the
      level of the CSF, already above mentioned; the MRI showed a hypersignal at the
      low dorso-lumbar level and at the terminal cone without any sign of tumoral
      processus, associated to an abnormal contrast at the level of meninges. All of
      that revealed a significant aspect of a meningo-myelo-radiculitis. In front of
      the various negative sero-bacteriological, viral, parasitic test, of the
      unresults of the research of any systemic symptom, one decided to perform a
      neurosurgical intervention to get a biopsy. So was revealed the presence of ovoid
      elements PAS+with a lateral spur and parasitic aspect. Consequently the diagnosis
      of bilharziosis was established. A cure of Praziquantel has been prescribed: 3
      tablets/day for 10 days, and four more cures at an interval of one month, all of
      them associated to a long term corticotherapy. Any diminution of the dosis
      entailed an increase of the painful symptomatology. Because of the perennial
      posterior cordal painful symptom, the patient has shown a depressive
      reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139435
TI  - [Recent injuries of the spinal apropos of 496 cases, 30 autopsies].

PMID- 8139436
TI  - [Malaria morbidity and therapeutic efficacy of antimalarials. Study conducted in
      the Dakar region].
AB  - During November and December 1992, the authors surveyed the malaria morbidity and
      the drugs efficiency in an urban area of Dakar region. Malaria represented 13.68%
      of the fevers in Dakar district and 12.4% in Pikine. The mean parasitic density
      was evaluated at 5000/mm3. Good efficiency of antimalarial drugs were noted but
      chloroquine-resistance is present with 24% of prevalence.

PMID- 8139437
TI  - [Mortality caused by traffic accidents at the Traumatology and Orthopedics Center
      of Grand-Yoff. A 2-year study. Apropos of 156 cases].
AB  - Most of road accident casualties are directed to the "Centre de Traumatologie et
      d'Orthopedie" between March 1989 and March 1991, the emergency Department
      received 8250 casualties treated by a team core comprising anesthetist-intensive
      care doctors and orthopaedic surgeons supplemented when necessary by other
      specialists. Out of those 8250 casualties aged 30 in average, 156 died at the
      hospital in varying time limits. The authors of present study intend to assess
      the efficiency of the medical and surgical care provided to identify the most
      frequent death causes and to suggest ways means of reducing the death toll.
      Forensic autopsies revealed the following lesions by order of prevalence: brain
      traumas 68, polytraumatisms 58, cervical vertebral traumas 13, abdomen traumas 7,
      polyfractures 3. In despite of the working conditions improvement at this
      specialized center (intensive care, technical facilities and staff) the mortality
      rate remains high, specially in polytraumatisms and brain traumas. The authors
      insist upon the need for a medically assisted transport unit which would take
      care of casualties before their arrival at hospital and for the acquisition of
      modern diagnosis means (tomodensitometry).

PMID- 8139438
TI  - [Treatment of leprotic neuritis. Exclusive medical treatment or combined with
      decompression].
AB  - The authors consider the evolution of the treatment of leprotic neuritis based on
      homogenous series of numerous observations (a minimum of 250-300). These
      observations are well registered and documented with some results dimensioned by
      the classical A. L. E. R. T. tests carried out at intervals of time and verified
      by comparison between series only medical treatment and series of medico-surgical
      treatment. Considering some remote results and some comparative series, the
      indications of the exclusive medical treatment have been well defined, and the
      ones of the surgical decompression have been reduced. The early case finding of a
      leprotic neuritis by the mean of easy methods as well as its monitoring during
      its early specific treatment is essential. By this way we get an important
      proportion of functional results: satisfactory (50 p.c.) or interesting (20
      p.c.). In the case of painful hypertrophia, the complementary decompression
      secure not only the functional recovery of mortricity, but also the epicritic
      sensibility.

PMID- 8139440
TI  - [Epidemiologic distribution of HIV2 human immunodeficiency virus infection in sub
      Saharan Africa].
AB  - This text presents the results of an analysis of the distribution and evolution
      of the HIV2 infection in Africa South of Sahara. The serological data collected
      in selected groups of the population suggest that the virus is very rare in the
      East and the South of the continent, except in Mozambic where it is found
      everywhere, but on a low level. The infection is also rarely depisted in West
      Central Africa; however an epidemic could affect the North of angola. HIV2 is
      probably an old host of some West African collectivities. Now the infection is
      often sporadic in the general population except in a little regional foci in
      Guinea-Bissau. On the contrary, high prevalences are observed in many groups of
      prostitutes. The epidemiological situation has been stable since 1985-86. At
      least in West Africa, the only new fact of the recent past could be that the
      infection became apparent to the physicians.

PMID- 8139439
TI  - [Acute bacterial pneumonia in retroviral infections. Epidemiologic, clinical,
      radiologic, bacterial and developmental aspects].
AB  - From a prospective study starting January 8 to 1990 October 20, the authors
      discuss 70 cases of acute pneumopathy, supposed to be bacteriologic in patients
      infected by HIV. The observed pneumopathies are more frequent in young adults,
      with a pic between 20 to 40 (67.15 p.c). The positivity rate of hemocultures was
      estimated at 17.14 p.c. with a clear predominance of non typhic Salmonellae. The
      evolution observed, generally favourable at 72.85 p.c was fatal in 17.15 p.c.

PMID- 8139441
TI  - [Seroprevalence of human immunodeficiency virus infection among pregnant women in
      Brazzaville].
AB  - A serological study aimed at measuring the distribution and extent of the HIV
      infection in the population was carried out from 1 October to 30 November 1990
      among 689 pregnant women seen during prenatal consultations in the Health Centers
      of the National Social Security Service. Serological tests according to ELISA
      method were used. They were anonymous and uncorrelated. Specific seroprevalence
      was found to be high among young women between 20 and 29 years (10.10%) and among
      nulliparous women. Some correlation was observed between the parity and the
      seropositivity; the seroprevalence was higher among nulliparous women (chi 2 =
      52.4; ddl = 4; p < 0.001). The authors recommend the reinforcement of preventive
      measures and the establishment of counselling in Mother and Child Health Care
      Centers (MCH).

PMID- 8139442
TI  - [Reoperations for mechanical complications of femoral osteosynthesis. Analysis of
      20 cases].
AB  - Based on a study of 220 femoral osteosynthesis, the results of 20 second surgical
      operations because of mechanical complications sat in 19 patients. These
      complications occurred on 15 screwed plates (6 breakings, 6 angulations, 3
      dismounting) and 5 nailings (4 proximal migrations, 1 angulation). The critical
      analysis about the first osteosynthesis showed some technical error in several
      cases. Pseudarthrosis (9.2 p.c.) was observed in all mechanical complications at
      the plates A second surgical operations, thanks to a new osteosynthesis
      associated, in 8 cases, with a cortico-spungoid osseous graft led to 85 p.c. of
      good and very good results and 15 p.c. of satisfactory results. No post surgery
      complication was observed.

PMID- 8139443
TI  - [Diagnostic problems apropos of 2 clinical cases of lumbar Pott's disease].
AB  - Two cases of POTT's disease without radiological osteoarticular destructions have
      been diagnosed from a psoas and a dorsal abscess. Bacteriology and histology were
      negative at the beginning, then became positive after a long evolution of the
      wound. The recommendation is to think of POTT's disease when confronted with any
      paravertebral abscess, with or without radiological signs and to repeat the
      bacteriological and histological tests if necessary.

PMID- 8139444
TI  - [Mobile pedicled skin flap in one-stage repair of stenoses of the male urethra].
AB  - A simple technique is presented for the management of male urethral strictures
      through one-stage urethroplasty using a mobile pedicled skin flap, be it scrotal
      or penial skin. The distinctive feature of this technique is the use of a very
      versatile pedicle, with good blood supply carved out from the subcutaneous cell
      tissue and the dartos. Depending on the case encountered, our management
      technique offers a choice of two kinds of plasty: the widening patch, meant to
      widen the urethral canal, and the tubular graft, which consist in forming a
      tubular shaped graft in order to replace part or the entire urethra. Since 1984,
      we have performed this technique 237 times. All of the patients underwent regular
      check-up, and results, on the anatomical and functional aspect, were very
      satisfactory. Our experience in the use of this management technique has
      convinced us of its efficiency and reliability, particularly for infected,
      fistulated, recurrent and extensive urethral strictures.

PMID- 8139445
TI  - [Materno-fetal infection caused by Haemophilus influenzae].
AB  - Neonatal infection due to Haemophilus influenzae is a rare cause of neonatal
      infection. The authors report a case associated with premature membrane rupture.

PMID- 8139446
TI  - Simultaneous measurement of both lipid and lactate in isolated rat hearts by 1H
      NMR spectroscopy.
AB  - Myocardial lipid and lactate levels are sensitive indicators of biochemical
      status: lipid levels have been shown to increase in response to high fat diets,
      disease or metabolic stress and elevated lactate levels are indicative of reduced
      oxygen supply. Selective measurement of lactate or lipid levels by 1H NMR is not
      straightforward since both the lactate methyl group and lipid methylene groups
      resonate at 1.3 ppm. We have overcome this difficulty by employing spectral
      editing techniques to observe both lipid methylene and lactate methyl resonances,
      and have measured lipid and lactate levels in perfused rat hearts during control
      perfusion and in response to metabolic stress. Lactate increased during ischemia
      and decreased during reperfusion, and the ischemia-induced increase is inhibited
      by iodoacetate, as expected. In contrast, lipid levels increased during ischemia
      and remained elevated during reperfusion. Hearts from rats fed high fat diet show
      elevated lipid levels during control perfusion. Data obtained by 1H NMR are
      consistent with biochemical data, validating the technique.

PMID- 8139448
TI  - Estimation of metabolite concentrations from localized in vivo proton NMR
      spectra.
AB  - The LCModel method analyzes an in vivo spectrum as a Linear Combination of Model
      spectra of metabolite solutions in vitro. By using complete model spectra, rather
      than just individual resonances, maximum information and uniqueness are
      incorporated into the analysis. A constrained regularization method accounts for
      differences in phase, baseline, and lineshapes between the in vitro and in vivo
      spectra, and estimates the metabolite concentrations and their uncertainties.
      LCModel is fully automatic in that the only input is the time-domain in vivo
      data. The lack of subjective interaction should help the exchange and comparison
      of results. More than 3000 human brain STEAM spectra from patients and healthy
      volunteers have been analyzed with LCModel. N-acetylaspartate, cholines,
      creatines, myo-inositol, and glutamate can be reliably determined, and abnormal
      levels of these or elevated levels of lactate, alanine, scyllo-inositol,
      glutamine, or glucose clearly indicate numerous pathologies. A computer program
      will be available.

PMID- 8139447
TI  - Sensitivity and localization enhancement in multinuclear in vivo NMR spectroscopy
      by outer volume presaturation.
AB  - Sampling of the entire brain tissue in 1H NMR metabolic studies is complicated by
      the presence of intense pericranial lipid and tissue water resonances, which can
      obscure metabolite resonances. This study extends the concept of localization by
      outer volume suppression (OVS) to achieve fully conformal in vivo localization,
      sampling at least 95% of rat brain with complete elimination of pericranial
      lipids. This has permitted acquisition of lipid-free short echo time (7.5 ms),
      high spatial resolution 2D spectroscopic images exhibiting high sensitivity and
      information content in relatively short measurement time (68 min). Incorporation
      of spatially tailored OVS into existing methods (e.g., DRESS, STEAM, PRESS)
      extends their localization efficiency and performance. Two single spin-echo
      localization sequences have been described that attain much shorter echo times or
      achieve better water suppression than PRESS. One of these sequences allows
      editing and relaxometric studies of J-coupled spins. The methods described are
      suitable for in vivo localization of most tissues and can be applied with any
      biologically important nucleus.

PMID- 8139449
TI  - In vivo fluorine-19 magnetic resonance spectroscopy of cerebral halothane in
      postoperative patients: preliminary results.
AB  - This study reports the use of 19F MRS to study halothane in the brain of eight
      patients recovering from halothane anesthesia of short duration. Resonances
      attributable to halothane were observed up to 90 min after withdrawal of the
      anesthetic agent. The signal-to-noise ratio for an unlocalized spectrum acquired
      using a 6 cm surface coil was typically 20 with data collection times of 2 min.
      In seven patients a single resonance was seen with a mean (+/- SD) chemical shift
      of +43.3 (+/- 1.8) ppm, referenced to NaF at 0 ppm. This resonance exhibited a T1
      value of between 0.5 and 1 s, and a T2* (estimated from the linewidth of the
      resonance) between 3.5 and 10 ms. In one patient two resonances were observed
      with chemical shifts of +38 and +41 ppm. Because we cannot exclude the
      possibility that this was due to field inhomogeneity, the significance of the
      last finding is uncertain. However, phantom studies show that the chemical shift
      of halothane in different environments (such as water, olive oil, methanol, and
      lecithin) can vary to an extent that accounts for the two resonances seen in our
      patient. These results demonstrate the feasibility of in vivo 19F MRS studies of
      fluorinated volatile agents in humans. The potential for clinical 19F MRS of
      fluorinated anesthetics is discussed.

PMID- 8139450
TI  - A molecular theory of relaxation and magnetization transfer: application to cross
      linked BSA, a model for tissue.
AB  - Homogeneous soft tissue, as regards its magnetic relaxation properties, is well
      modeled by solutions of cross-linked protein (see Koenig and Brown, Prog. NMR
      Spectr. 22, 487 (1991)). Interactions at the solute-solvent interface alter the
      hydrodynamics of solvent water, and also couple the solute and solvent proton
      Zeeman energy reservoirs, giving hydrodynamic and cross-relaxation contributions
      to water proton relaxation that respond differently to deuteration of solvent. We
      report measurements of the magnetic field dependence of 1/T1 of water protons in
      cross-linked bovine serum albumin (BSA), for partially deuterated solvent and, in
      order to separate these two contributions, of 1/T1 of deuterons. The major
      experimental finding is that, in addition to recently identified water-binding
      sites on protein (covering approximately 0.2% of the surface) with water
      lifetimes of about 1 microsecond, there is another group of sites with lifetimes
      of about 23 ns, covering approximately 2% of the surface, which are evident in
      both proton and deuteron data. In addition, we have formulated a theory of
      interfacial proton-proton magnetic interactions which--with these four
      parameters, plus two that quantify the protein-water coupling at each site--can
      account for all the proton and deuteron data, in both native and cross-linked
      BSA.

PMID- 8139451
TI  - Relaxometry, animal biodistribution, and magnetic resonance imaging studies of
      some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester
      complexes.
AB  - The Gd3+ complexes of three new phosphorus containing tetraaza macrocycles
      (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene ethylphosphonic
      acid), H4DOTEP; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene
      phosphonic acid monoethylester), H4DOTPME; and the corresponding n-butyl ester,
      H4DOTPMB) were prepared and examined for possible use as MRI contrast agents.
      Although thermodynamically and kinetically less stable than Gd(DOTA)- in saline
      and HSA solution, the stability of these new macrocyclic complexes appears to be
      sufficiently high for in vivo applications. NMRD relaxivity profiles of the three
      complexes indicate that the number of inner sphere water molecules for these
      chelates is < or = 1 and that the more hydrophobic chelate, Gd(DOTPMB), binds to
      human serum albumin (HSA). Biodistribution studies of the radioactive 153Sm or
      159Gd chelates in rats, gamma imaging of the 153Sm chelates in rats, and proton
      MRI studies of the nonradioactive Gd3+ chelates in rabbits all indicate that the
      DOTPMB complexes accumulate preferentially in the liver, spleen, and small
      intestines while the more hydrophilic DOTEP and DOTPME complexes appear to
      display renal clearances similar to other low molecular weight contrast agents.

PMID- 8139452
TI  - MR angiography using velocity-selective preparation pulses and segmented gradient
      echo acquisition.
AB  - We describe a cardiac-gated MR angiographic imaging method that employs velocity
      selective preparation (VSP) pulses in conjunction with segmented gradient-echo
      acquisition and subtraction to produce images that, ideally, contain no signal
      from stationary tissues and display vessels with a signal intensity that is
      dependent on the velocity of the blood in the vessels. The novel features of this
      method are a) it acquires several phase-encoding values/application of a single
      VSP pulse, b) it uses subtraction to eliminate signal that is not sufficiently
      suppressed by the VSP pulses, and c) it uses VSP pulses that are synchronized
      with the cardiac cycle so it can be used to produce ghost-free images of
      pulsatile blood. An advantage of this sequence is that it detects a signal that,
      after preparation, is relatively unaffected by changes in blood velocity. This
      leads to a large signal-to-noise ratio for all the phase-encoding values, a
      reduction of ghosting artifacts, and the ability to visualize blood that is in
      motion for only a short time during the cardiac cycle. Because the signal is
      prepared during peak flow, venous signal can be suppressed by making the sequence
      sensitive to high velocities. An additional advantage of this sequence is that it
      permits sampling with a short TE because the velocity-encoding gradient can be
      applied in a preparatory interval. Signal loss that results from dephasing during
      the longer TE preparation interval can be reduced or eliminated by allowing the
      dephased spins to flow out of the region of complex flow, and perhaps out of the
      field-of-view, by introducing a delay between the finish of the VSP pulse and the
      beginning of data acquisition.

PMID- 8139453
TI  - Measurement of regional blood oxygenation and cerebral hemodynamics.
AB  - An echo planar linewidth mapping technique, Shufflebutt, has allowed temporal
      measurements of changes in linewidth caused by static inhomogeneities (delta
      LWSI) and transverse relaxation rate (delta R2) in models of hypoxia and
      hypercapnia. We demonstrate these changes are due to intravascular susceptibility
      differences/(delta chi) between the blood and tissue. Contrast agent injections
      at a delta chi equivalent to that of deoxygenated blood showed a twofold
      difference between the contrast agent and physiological anoxia values.
      Hypercapnia decreased both delta LWSI and delta R2 consistent with an increase in
      blood oxygenation. We attribute these findings to constant oxygen extraction
      during an increase in blood flow, resulting in less deoxygenated venous blood and
      thus reduced delta chi. For in vivo perturbations we found that delta R2/delta
      R2' approximately 0.33, a ratio much different from that measured in whole blood
      phantoms (delta R2/delta R2' approximately 2). This demonstrates that signal
      changes in these studies are produced predominantly by dephasing of extravascular
      protons due to field inhomogeneities produced by intravascular deoxygenated
      hemoglobin (deoxyHb).

PMID- 8139454
TI  - Flow compensation in MRI using a phase-corrected real reconstruction.
AB  - Flow- and motion-related artifacts are problematic in clinical MR imaging. In
      this paper we discuss the utility of a phase-corrected real reconstruction to
      reduce flow artifacts. This technique is particularly useful when flow
      compensation pulse sequences may not be possible, such as when a very short echo
      delay or small field-of-view is desired. We will demonstrate that the phase
      corrected real reconstruction provides superior results to the magnitude
      reconstruction either used alone or in conjunction with existing flow
      compensation techniques.

PMID- 8139455
TI  - Spatially selective RF pulses and the effects of digitization on their
      performance.
AB  - Spectrometers make use of D/A converters to generate RF and gradient shapes. This
      paper examines by exact simulations the time and amplitude digitization effects,
      inherent to the use of D/A converters, on the performance of amplitude modulated
      (AM) frequency selective RF pulses. By making use of Fourier theory and the small
      tip angle approximation, an approximate model of these effects on the
      magnetization slice profiles is derived and verified for several pulse types by
      computer simulations. This approximate model will be used to derive requirements
      for D/A converters with respect to spatial localization. The dynamics of the spin
      system allows pulse width modulation (PWM) as an alternative to AM for pulse
      envelope encoding. The effects of PWM on the slice profile are examined and
      compared with conventional AM pulses. It is shown by simulation and measurement
      that adiabatic PWM pulses can be found. In contrast to AM modulated adiabatic
      pulses, adiabatic PWM pulses have side bands with the same slice quality as the
      main slice and might therefore be useful as multislice selective pulses.

PMID- 8139456
TI  - 31P transverse relaxation times of ATP in human brain in vivo.
AB  - 31P MRS examinations of the brain of 10 healthy volunteers were performed to
      determine T2 of the coupled ATP signals by use of the localized 90 degrees-TE/2
      2662-TE/2-acq frequency selective spin echo sequence for elimination of phase and
      intensity distortions. The T2 relaxation times obtained are much longer than
      usually assumed: gamma-ATP: 89 +/- 9 ms; alpha-ATP: 84 +/- 6 ms; beta-ATP: 62 +/-
      3 ms.

PMID- 8139457
TI  - A rapid interleaved method for measuring signal intensity curves in both blood
      and tissue during contrast agent administration.
AB  - A method has been developed that uses dynamic MR imaging to measure
      simultaneously the changes in signal intensity due to paramagnetic contrast agent
      in blood and tissue, using interleaved single-angle projection and imaging
      sequences. The basic projection/image sequence has a projection time resolution
      of 50 ms and can measure rapid changes in the blood signal intensity. Variants
      with a tissue suppression slab have time resolutions of 57 or 75 ms. Orientation
      of the projection and image planes can be defined independently. This technique
      will facilitate functional measurements using MR contrast agents, allowing the
      blood input function to be determined with excellent time resolution.

PMID- 8139458
TI  - Asymmetric single-turn solenoid for MRI of the wrist.
AB  - A single-turn solenoid, lacking the conventional cylindrical or rectangular
      symmetry, was constructed for magnetic imaging of the human wrist at 1.5 Tesla.
      As is characteristic of single-turn solenoids, this wedge-shaped geometry
      solenoid was found to have a high filling factor and quality factor, as well as
      produce images with a favorable signal-to-noise ratio. The radio frequency (RF)
      transmitter power required to produce a 90 degrees pulse in the solenoid was 130
      mW. The asymmetric solenoid had a small variation in the intensity of the RF
      field across its volume, which is characteristic of symmetrical single-turn
      solenoids. The combination of these four properties of the coil resulted in the
      production of excellent 1.5-mm thick anatomical images of the wrist.

PMID- 8139459
TI  - Resolution enhanced NMR spectroscopy in biological systems via magnetic
      susceptibility matched sample immersion chambers.
AB  - A technique is described which reduced the magnetic susceptibility induced line
      broadening in NMR spectra obtained from three biological systems at 4.7 Tesla.
      Proton spectra from a sealed suspension of HL60 leukemic myeloblasts yielded
      minimum linewidths of 1.3 Hz at 200 MHz (0.0065 ppm) after 10 min of automated
      shimming. 31P spectra from an in vivo murine MCa mammary carcinoma yielded a well
      resolved phosphorylcholine resonance without proton decoupling and with the
      resistive shim coil currents set to zero. 31P spectra from a perfused suspension
      of RIF-1 fibrosarcoma cells exhibited a gamma-nucleoside triphosphate resonance
      which was resolved into purine and pyrimidine components.

PMID- 8139460
TI  - NMR visibility studies of N-delta proton of proximal histidine in deoxyhemoglobin
      in lysed and intact red cells.
AB  - Recent in vivo 1H MRS studies of muscle oxygen levels by means of myoglobin (Mb)
      oxygenation have necessitated an investigation of the possible contamination from
      deoxy-hemoglobin (Hb). To determine the contribution of Hb in these NMR
      measurements, we studied the NMR visibility of histidyl N-delta proton of Hb in
      lysed and intact RBC (red blood cell) suspensions. We found that the visibility
      of deoxy-Hb was significantly lower in intact RBCs (ca. 16%) than the solution
      form at an equivalent concentration of beta heme-iron, even though the visibility
      of deoxy-Hb from lysed RBC and deoxy-Mb was almost identical. Our study also
      shows that visibility increases with RBC swelling. Based on the difference in
      concentration and compartmentation, we conclude that less than 17% contribution
      from Hb is expected in Mb measurements in vivo. The possible mechanisms which
      cause the low visibility of Hb in RBCs are discussed.

PMID- 8139461
TI  - A functional MRI technique combining principles of echo-shifting with a train of
      observations (PRESTO).
AB  - We present a fast MRI technique sensitized to microscopic susceptibility effects.
      The method combines elements of echo-shifted gradient-recalled MR imaging (TE >
      TR) with the acquisition of multiple k-space lines within a single TR-period. The
      sequence results in a much reduced imaging time as compared with conventional
      gradient-echo MRI methods. The feasibility of the method is demonstrated for
      susceptibility bolus tracking in the cat brain using an imaging time of 153 ms.
      The relative cerebral blood volume maps created with this method are comparable
      with those obtained with conventional methods.

PMID- 8139462
TI  - Development of Colombian isolates of Leishmania (Viannia) panamensis, Le. (V.)
      guyanensis and Le. (V.) braziliensis in the sandfly Lutzomyia intermedia (Lutz &
      Neiva, 1912) under experimental conditions.
AB  - The development of Colombian Leishmania species of the subgenus Viannia in
      Lutzomyia intermedia was similar to that observed with Brazilian Le. (V.)
      braziliensis: colonization of the pylorus by paramastigotes; promastigotes in the
      midgut and massive infection of stomodeal valve. Difference was observed in the
      number of paramastigotes colonizing the pylorus, which was smaller in Colombian
      Leishmania species than Brazilian Le. braziliensis.

PMID- 8139463
TI  - Acetylated alpha-tubulin in Trypanosoma cruzi: immunocytochemical localization.
AB  - We have used monoclonal antibodies specific for acetylated and non-acetylated
      alpha-tubulin to localize microtubules containing acetylated alpha-tubulin in all
      developmental forms of the life cycle of Trypanosoma cruzi. This was demonstrated
      using immunofluorescence and by transmission electron microscopy of thin
      sections, negative stained cells, and replicas of whole Triton X-100 extracted
      cells immunolabeled with antibody-gold complex. The antibody specific for
      acetylated alpha-tubulin (6-11B-1) binds to the flagellar, as well as to the sub
      pellicular microtubules. The extent of labeling of the sub-pellicular
      microtubules with the monoclonal antibody recognized alpha-acetylated tubulin was
      smaller than that observed with the antibody which recognizes all tubulin
      isoforms. In relation to the developmental forms, the extent of labeling of the
      microtubules with antibody 6-11B-1 was larger in epimastigote and trypomastigote
      than in amastigote forms. Incubation of the parasites for 1 h at 0 degrees C or
      in the presence of either colchicine or vinblastine did not interfere with the
      sub-pellicular microtubules. These observations, in agreement with those reported
      for Trypanosoma brucei brucei (Schneider et al., 1987; Schulze et al., 1987;
      Sasse & Gull, 1988) indicate that the sub-pellicular microtubules of
      trypanosomatids represent stable microtubules containing acetylated alpha-tubulin
      (or the alpha 3-tubulin isotype).

PMID- 8139464
TI  - Difference in susceptibility to lysis between clones of the Y strain of
      Trypanosoma cruzi.
AB  - Three clones isolated from the Y strain of Trypanosoma cruzi--YP1, YP2 and YP3-
      were adapted to in vitro cultivation in VERO cells. The recovery of the parasites
      from the Y strain and clone YP3 was similar after 24 hr of contact with cells
      (3.2% and 2.7%, respectively) and much lower than the recovery of clones YP1 and
      YP2 (56.7% and 60.0% of inoculum, respectively). After five days incubation, the
      ratio Trypomastigotes/Amastigotes released into the supernatants was about 90/10
      for clone YP1, YP3 and Y strain, and 50/50 for clone YP2. After nine days, the
      ratio was 62/38 for clone YP1, 97/3 for clone YP3, 81/19 for Y strain and 50/50
      for clone YP2. The susceptibility of tissue culture derived trypomastigotes (TCT)
      to lysis in the presence of chronic chagasic human sera and human complement was
      assessed using Complement Mediated Lysis reaction (CML). Trypomastigotes from
      clone YP2 were consistently less susceptible to CML (% lysis less than 20), than
      parasites from the other clones and Y strain. Parasites of clone YP3 had
      susceptibility to CML comparable to that of the Y strain (about 70%), while TCT
      of clone YP1 had intermediary susceptibility (40%).

PMID- 8139465
TI  - Intestinal protein absorption in malnourished mice with acute schistosomiasis
      mansoni.
AB  - Intestinal protein absorption was studied in undernourished albino Swiss mice
      with acute schistosomiasis mansoni. Undernutrition was induced by feeding mice
      with the Regional Basic Diet (RBD) ingested by human populations in Northeast
      Brazil, an experimental model previously developed in our laboratory. Weaning
      mice were infected with 40 cercariae and compared to undernourished non-infected
      mice and/or to infected mice fed a balanced control diet. Apparent and True
      Protein Absorption Coefficients were determined by nitrogen balance during five
      consecutive days ending at the 63rd day of the trial (acute phase of murine
      schistosomiasis). Fecal metabolic nitrogen (FMN) was determined after
      administration of a non-protein diet and was also calculated through linear
      regression. Our results showed a reduced protein absorption in non-infected RBD
      fed mice as compared to mice fed a casein control diet. Infection with
      Schistosoma mansoni had apparently no effect on intestinal protein absorption in
      well-nourished mice. However, infection seemed to interfere with protein
      absorption in under-nourished animals, since the lowest absorption ratios have
      been detected among RBD-fed infected mice. A brief discussion is made on the
      advantages of using the method of linear regression for the determination of FMN.

PMID- 8139466
TI  - Evaluation of virulence factors in environmental isolates of Vibrio species.
AB  - Strains of Vibrio parahaemolyticus, Vibrio fluvialis and Vibrio mimicus isolated
      from seafood and seawater were examined for characteristics related to
      infectivity, such as enzymatic activity and animal assays. All strains hydrolysed
      DNA, starch, gelatin and chitin. Variable results were obtained with the
      haemolysin, chondroitin, collagen, elastin and lecithin tests. Production of
      thermostable direct haemolysin by V. parahaemolyticus was detected in 7.1%
      strains derived from seafood and 2% from seawater. In the animal assays, strains
      of V. fluvialis showed positive results at skin PF (75%), mouse lethality (100%),
      but no fluid accumulation in the suckling mice model was noted. Concerning V.
      mimicus, results showed skin PF (100%), mouse lethality (100%) and fluid
      accumulation in suckling mice (66.6%).

PMID- 8139467
TI  - Laboratory evaluation on pathogenic potentialities of Vibrio furnissii.
AB  - Sixteen strains of Vibrio furnissii recovered from 16 Brazilian patients with
      diarrhea were screened for virulence-associated factors. All strains were non
      invasive, non-fimbriated, and did not produce either enterotoxins or cholera-like
      toxin. In contrast, most were hemolytic on blood agar and their broth-culture
      supernatants damaged HeLa cell monolayers. These cytolysins, as accepted for
      other enteropathogenic members of the family Vibrionaceae, might be determinants
      of pathogenicity in V. furnissii-mediated enteritis.

PMID- 8139468
TI  - Inflammatory cutaneous reaction induced by the lectin of Dioclea grandiflora
      (Mart.).
AB  - The lectin from Dioclea grandiflora (Mart.) that selectively binds glucose and
      mannose, when subcutaneously injected in mouse induces an inflammatory cutaneous
      reaction whose histological analysis reveals an hemorrhagic ulceration with
      exudative reaction accompanied by an influx of polymorphonuclear leukocytes and
      giant cells. The presence of lymphocytes and plasma cells in the lesion was
      insignificant. In order to characterize the in vivo action of inflammatory
      factors generated by this lesion, distinct lines of mice were used: high and low
      antibody responder mice; the genetically selected mice to the acute phase of
      inflammatory reaction; lines of mice deficient in C5, a protein of the complement
      system. It is shown that the lectin of D. grandiflora acts as an inflammatory
      agent probably promoting exocytosis and release of mediators.

PMID- 8139469
TI  - Piry virus antibodies in inhabitants of Rio de Janeiro.

PMID- 8139470
TI  - Human cutaneous leishmaniasis due to a new enzymatic variant of Leishmania
      (Viannia) braziliensis occurring in Pernambuco, Brazil.

PMID- 8139471
TI  - Delayed hypersensitivity skin-test using Leishvacin for epidemiological survey of
      canine cutaneous leishmaniasis in a rural area of Minas Gerais state, Brazil.

PMID- 8139472
TI  - Elevated endothelin-1 levels after cigarette smoking.
AB  - The effect of short-term nicotine consumption on endothelin-1 (ET-1) levels was
      studied in 10 male healthy smokers. Volunteers smoked in random order on 3
      separate days a low-tar cigarette or a high-tar cigarette, or were studied
      without having smoked (no-cigarette experiment). ET-1, corticotropin, and
      cortisol levels, heart rate, and blood pressure were determined before and 1, 3,
      5, 10, 20, and 30 minutes after smoking. In contrast to results obtained after
      smoking a low-tar cigarette or not smoking, smoking a high-tar cigarette resulted
      in a significant increase in ET-1 levels within 10 minutes, followed by an
      increase in corticotropin levels within 20 minutes after smoking. Thirty minutes
      after smoking, cortisol levels were higher after a high-tar cigarette compared
      with a low-tar cigarette or no smoking. Increases in heart rate and systolic
      blood pressure were likewise higher after smoking a high-tar cigarette than after
      smoking a low-tar cigarette. In conclusion, it is tempting to speculate that ET-1
      may indeed act as the long-searched-for link between vasopressin and
      corticotropin-releasing hormone (CRH) and thus play an essential role in the
      stimulation of the hypothalamic-pituitary-adrenal axis. In addition, these
      results suggest that the increase in the level of ET-1, a powerful
      vasoconstrictor and mitogen, may play an important part in the disease mechanisms
      of atherosclerosis arising from smoking.

PMID- 8139473
TI  - Postprandial amplification of lipoprotein abnormalities in controlled type II
      diabetic subjects: relationship to postprandial lipemia and C-peptide/glucagon
      levels.
AB  - Lipoprotein abnormalities, mainly high very-low-density lipoprotein (VLDL) and
      low high-density lipoprotein (HDL) levels, increase the risk of coronary heart
      disease (CHD) in type II diabetic patients. To investigate the relationship
      between these lipoprotein abnormalities and the postprandial (PP) lipid-clearing
      capacity, triglyceride (TG) and hormonal levels were determined hourly up to the
      4th hour after a mixed meal containing 32.5 g lipids/m2 body surface in 14
      treated non-obese type II diabetic patients with adequate nutritional and
      glycemic control (hemoglobin A1C [HbA1C] < 7%) and in 12 healthy subjects matched
      for age, sex, and body mass index (BMI). Mean cholesterol levels did not differ
      between patients and controls, with fasting TG moderately increased in diabetics
      (140 +/- 70 v 66 +/- 34 mg/dL, P < .01). Whereas fasting TG levels in patients
      showed a continuous distribution from 55 to 250 mg/dL, postprandial TG clearly
      identified two different subgroups. A "high-responder" or hypertriglyceridemic
      subgroup (HTG) showed PP TG levels significantly higher than control levels (290
      +/- 62 v 106 +/- 41 mg/dL, P < .001), with higher fasting TG as well (181 +/- 52,
      P < .01), whereas both fasting and PP TG levels were not different from control
      levels in the normotriglyceridemic (NTG) diabetic subgroup. The magnitude of the
      PP triglyceridemic area showed a negative correlation with HDL2 cholesterol (r =
      .66, P < .001) and a positive correlation with PP HDL2 TG enrichment (r = .80, P
      < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139474
TI  - Effects of systemic infusions of endotoxin, tumor necrosis factor, and
      interleukin-1 on glucose metabolism in the rat: relationship to endogenous
      glucose production and peripheral tissue glucose uptake.
AB  - This study was performed to characterize and compare the actions of insulin on
      hepatic glucose production and peripheral glucose utilization during infusions of
      endotoxin, tumor necrosis factor (TNF), interleukin-1 (IL-1), and a combination
      of IL-1 and TNF in the rat. The euglycemic hyperinsulinemic clamp technique was
      combined with a primed-constant tracer infusion of high-performance liquid
      chromatography (HPLC)-purified 3H-3-glucose for estimation of whole-body glucose
      appearance and utilization rates; 14C-deoxyglucose (14C-DG) uptake was also
      measured in specific tissues following intravenous bolus administration. As
      expected, acute endotoxemia resulted in a significant reduction of glucose
      infusion during the clamp procedure (insulin concentration, 100 microU/mL),
      suggesting decreased insulin action. Similarly, infusion of TNF decreased the
      rate of glucose infusion necessary to maintain euglycemia. However, differences
      between endotoxin- and cytokine-treated rats were noted in whole-body glucose
      appearance (or disappearance) rates. Whereas endotoxin infusion predominantly
      decreased whole-body glucose uptake, suggesting diminished utilization in
      skeletal muscles, cytokine infusions were associated with a measurable hepatic
      glucose output despite hyperinsulinemia. In contrast, both cytokine and endotoxin
      administration decreased the rate of 14C-DG uptake by muscle tissue. These
      results demonstrate that TNF, IL-1, and endotoxin can induce a state of insulin
      resistance when infused continuously; the results also emphasize the complexity
      of regulation of glucose homeostasis during infection and sepsis.

PMID- 8139475
TI  - Glycogen turnover during refeeding in the postabsorptive dog: implications for
      the estimation of glycogen formation using tracer methods.
AB  - Recent 13C nuclear magnetic resonance (13C-NMR) studies in the anesthetized rat
      and perfused liver suggest that hepatic glycogen is simultaneously synthesized
      and degraded, even during combined hyperglycemia and hyperinsulinemia. The
      presence of glycogen turnover would confound efforts to study glycogen repletion
      with the use of tracer methods during feeding, particularly if the liver is not
      glycogen-depleted. To ascertain whether glycogen turnover occurs during normal
      feeding, we measured liver uptake of glucose in 10 awake, healthy, postabsorptive
      dogs with long-term arterial, portal, and hepatic venous catheters before and for
      3 hours after a meal of either glucose alone (1.5 g/kg) or glucose supplemented
      with crystalline amino acids (0.7 g/kg); the meal was labeled with D-[3
      3H]glucose and [U-14C]alanine. Liver glycogen level was measured in biopsies
      obtained before and at 180 minutes after the meal. The postabsorptive liver
      glycogen content was 4.3 +/- 0.9 g/100 g, and net hepatic glucose release
      averaged 1.8 +/- 0.3 mg/min/kg. Over the 3 hours following feeding, the liver
      took up glucose (0.37 +/- 0.14 and 0.33 +/- 0.16 g/kg body weight in dogs
      receiving glucose and glucose with amino acids, respectively). At 3 hours,
      glycogen synthesis from D-[3-3H]glucose in the two groups averaged 0.24 +/- 0.09
      and 0.22 +/- 0.05 g/kg, or approximately 15% of the ingested glucose load. 14C
      glucose also was found in liver glycogen, demonstrating ongoing hepatic
      gluconeogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139476
TI  - Relationship between improved postprandial lipemia and low-density lipoprotein
      metabolism during treatment with tetrahydrolipstatin, a pancreatic lipase
      inhibitor.
AB  - The effect of tetrahydrolipstatin (THL), a recently developed pancreatic lipase
      inhibitor, on fasting plasma lipid levels and postprandial lipoprotein and
      retinyl palmitate (RP) metabolism was studied in 17 hyperlipidemic subjects,
      using an oral RP fat load (8 hours, 50 g fat/m2). During therapy with THL,
      fasting plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and
      apolipoprotein (apo) B concentrations decreased by 8% (P = .006), 9% (P = .002),
      and 10% (P = .002), respectively. The postprandial plasma triglyceridemia, which
      was expressed as the area under the 8-hour triglyceride (TG) curve, improved by
      27% during THL therapy (P = .04) without changes in fasting plasma TG or high
      density lipoprotein (HDL) cholesterol levels. The improved postprandial
      triglyceridemia was accompanied by a 19% reduction in circulating levels of
      chylomicrons and chylomicron remnants, determined by the decreased areas under
      the 8-hour RP curves. The most likely mechanisms involved are decreased formation
      of chylomicrons by a decrease of intestinal TG absorption as a consequence of THL
      treatment, as well as reduced delivery of dietary lipid and fatty acids to the
      liver and subsequent upregulation of hepatic LDL receptors. In agreement with the
      latter mechanism, the decrease in postprandial lipemia expressed as delta area
      under the TG curve was significantly related to the decrease (delta) in LDL
      cholesterol level during THL treatment (r = .81, P = .0001). The present data
      indicated that pancreatic lipase inhibition improved postprandial lipoprotein
      metabolism, which in turn resulted in lower plasma total and LDL cholesterol
      concentrations.

PMID- 8139477
TI  - Hyperlipidemia in streptozocin-diabetic hamsters as a model for human insulin
      deficient diabetes: comparison to streptozocin-diabetic rats.
AB  - Characteristics of the lipoprotein profile and metabolism of triglyceride-rich
      lipoproteins in diabetic hamsters were investigated to assess their suitability
      as a model for human diabetic hyperlipidemia. Diabetes was induced in the
      hamsters by intraperitoneal injection of streptozocin (30 mg/kg) for 3 days and
      compared with the results in streptozocin-diabetic rats (50 mg/kg intravenously).
      Similar degrees of hyperglycemia and hypoinsulinemia were observed 8 to 10 days
      after the final streptozocin injection in both groups. Fasting plasma lipid
      concentrations were about 2.5 times greater in hamsters than in rats. Plasma
      cholesterol was principally associated with high-density lipoprotein (HDL) in
      both rodents, although the distribution in very-low-density lipoprotein (VLDL)
      and low-density lipoprotein (LDL) was significantly greater in hamsters (44%)
      than in rats (13%). Diabetes increased the concentrations of triglyceride,
      cholesterol, and phospholipid 5.6- to 7.8-fold in hamsters, whereas it increased
      them only 1.3- to 1.6-fold in rats. Diabetic hamsters have a plasma lipoprotein
      profile similar to that of diabetic man, ie, triglyceride-rich lipoproteins are
      increased and HDL cholesterol is decreased. The concentration of HDL cholesterol
      was inversely correlated with the severity of hypertriglyceridemia (r = .76, P <
      .005). This combination of events does not occur in diabetic rats. Hamsters had a
      low level of apoprotein B-48-containing triglyceride-rich lipoproteins, although
      diabetes increased the estimated concentration by fourfold. In rats apoprotein B
      48 is the predominant form, but diabetes did not alter the relative proportion of
      apoprotein B isoforms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139478
TI  - Effect of glycemic control, race (white versus black), and duration of diabetes
      on reduced glutathione content in erythrocytes of diabetic patients.
AB  - We designed this study to examine whether uncontrolled hyperglycemia, duration of
      diabetes, or race (black v white) have any effect on glutathione levels in
      erythrocytes of type I diabetic patients. Hyperglycemia was assessed by measuring
      the level of hemoglobin A1c (HbA1c). Results show that erythrocytes of diabetic
      patients have a significantly lower glutathione level compared with those of age
      matched normal subjects (P < .004). We found a significant negative correlation
      (r = -.59, P < .001) between the degree of hyperglycemia and the level of reduced
      glutathione (GSH) in erythrocytes of diabetic patients. There was no significant
      relationship (r = -.29, P > .12) between the level of GSH in erythrocytes and the
      duration of diabetes. Erythrocytes of black diabetic patients had significantly
      lower levels of GSH (P < .05) than those of white diabetic patients. Using
      erythrocytes as a model, this study suggests that a lower level of GSH may have a
      role in the cellular damage and impaired insulin secretion in uncontrolled
      diabetic patients.

PMID- 8139479
TI  - The effect of dietary fat content on plasma noncholesterol sterol concentrations
      in patients with familial hypercholesterolemia treated with simvastatin.
AB  - The effects of a low-fat, low-cholesterol diet (LFD) or a higher-fat, higher
      cholesterol diet (HFD) on plasma concentrations of lipids, lipoproteins,
      lathosterol (an index of cholesterol synthesis rate), and plant sterols were
      determined in 19 patients with familial hypercholesterolemia (FH) treated with
      simvastatin. The study followed a randomized crossover design including two 8
      week diet periods. The LFD significantly decreased plasma lathosterol (-22%),
      cholesterol (-6%), low-density lipoprotein (LDL) cholesterol (-6%), and high
      density lipoprotein (HDL) cholesterol (-7%) levels compared with the HFD.
      Decreases in plasma lathosterol and LDL cholesterol concentrations in patients
      during the LFD were significantly correlated (r = .522, n = 19, P < .05). These
      results suggest that a LFD may enhance the decrease in cholesterol synthesis
      induced by simvastatin treatment, and in this way might contribute to the
      decrease in plasma cholesterol levels when the fat content of the diet is reduced
      in simvastatin-treated FH patients.

PMID- 8139480
TI  - Mechanism governing short-term fed-state adaptation to dietary protein
      restriction.
AB  - The mechanism governing short-term adaptation to dietary protein restriction was
      investigated in nine normal adults by measuring their metabolic response to a
      standard mixed meal, first while they were adapted to a conventional, high
      protein diet (day 1) and then again after they had eaten two low-protein meals
      (day 2). Urea appearance (measured as the sum of its urinary excretion and the
      change in body urea pool size), body retention of 15N-alanine included in each
      test meal, and whole-body protein turnover were calculated over the 9 hours
      following meal consumption on each day. Postprandial urea nitrogen appearance was
      5.05 +/- 0.26 g/9 h on day 1 and decreased to 4.16 +/- 0.31 on day 2 (P < .05).
      Whole-body N flux (Q), protein synthesis (S), and protein breakdown (B) all
      decreased significantly on day 2 as assessed using either urea or ammonium end
      product enrichments; however, recovery of 15N in the test meal as 15N-urea was
      similar on both days, approximately 22%. It is concluded that short-term
      metabolic adaptation occurs within two meals of reduced protein intake. The
      mechanism appears not to involve selectively an increased "first-pass" retention
      of dietary amino acids, but rather a general reduction in fed-state whole-body
      protein breakdown.

PMID- 8139481
TI  - Control of non-insulin-dependent diabetes mellitus partially normalizes the
      increase in hepatic efficacy for urea synthesis.
AB  - The relation of urea synthesis rate to blood alanine concentration was assessed
      in seven healthy controls and eight patients with non-insulin-dependent diabetes
      mellitus (NIDDM) before (hemoglobin A1c [HbA1c] = 9.9% +/- 1.9%, mean +/- SD) and
      after (HbA1c = 7.9% +/- 0.8%) improvement of metabolic control. Following an
      overnight fast, alanine was infused at a rate of 2 mmol/(h.kg body weight [BW]).
      The hourly rate of urea synthesis was determined as the urinary excretion of urea
      corrected for accumulation of urea in total body water (TBW) and intestinal
      hydrolysis. The functional hepatic nitrogen clearance (FHNC) was calculated as
      the slope of the linear relation of urea synthesis rate to blood alanine
      concentration. The glucagon level was increased by twofold at the first
      investigation, but was not increased at the second. The insulin level was
      moderately increased at both investigations. In controls FHNC was 21.8 +/- 4.4
      L/h, in poorly controlled patients it was increased to 36.6 +/- 4.3 L/h (P <
      .01), and following improvement of metabolic control it was not different from
      control levels at 28.6 +/- 4.3 L/h. By correlation analyses, FHNC was found only
      to be related to the fasting glucose value, albeit weakly (R2 = .39). In
      conclusion, hepatic kinetics of urea synthesis in poorly controlled NIDDM
      patients are changed in favor of increased conversion of alanine N to urea N at
      any amino acid concentration. This perturbation is partially normalized by
      improved metabolic control.

PMID- 8139482
TI  - Lipoprotein composition in insulin-dependent diabetes mellitus with chronic renal
      failure: effect of kidney and pancreas transplantation.
AB  - Chronic renal failure (CRF) in nondiabetics is associated with a number of
      lipoprotein abnormalities that place these patients at high risk for
      atherosclerosis. This study compared the lipoprotein composition of nondiabetic
      controls (n = 68) with that of patients with insulin-dependent diabetes mellitus
      ([IDDM] n = 13) and of patients with IDDM and CRF ([IDDM + CRF] n = 74). Six
      lipoprotein subfractions (very-low-density lipoprotein [VLDL], intermediate
      density lipoprotein [IDL], low-density lipoprotein [LDL], high-density
      lipoprotein-light [HDL-L], HDL-medium [HDL-M], and HDL-dense [HDL-D]) were
      isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The
      apolipoprotein (by reverse-phase high-performance liquid chromatography [HPLC])
      and lipid (by enzymatic assays) composition of each subfraction was determined.
      The only abnormalities found in IDDM patients were increases in IDL and HDL-L
      triglyceride (TG) levels and an increase in the HDL-L free cholesterol (FC)
      level. The IDDM + CRF group had multiple abnormalities including (1) elevated TG,
      apolipoprotein (apo) C-II, and apo C-III levels in all lipid subfractions; (2)
      elevated VLDL and IDL apo B, TG, FC, cholesterol ester (CE), and phospholipid
      (PL) levels (with an increased CE/TG ratio in VLDL only); (3) decreased HDL-M apo
      A-I, apo A-II, CE, and PL levels, but an increased HDL-D apo A-I level; and (4)
      decreased lecithin:cholesterol acyltransferase (LCAT) activity. Twenty-five of
      the IDDM + CRF patients underwent combined pancreas and kidney (P + K)
      transplantation, and 12 patients received only a kidney transplant. Lipoprotein
      composition was determined at 3, 6, and 12 months posttransplant. Both types of
      transplantation resulted in similar alterations in lipoprotein composition, even
      though there was essential normalization of blood glucose levels in most of the
      patients who received a pancreas transplant (hemoglobin A1C [HbA1C], 9.1% +/-
      1.1% v 5.7% +/- 0.3% at 12 months, P < .01). These posttransplant changes
      included (1) no improvement in the elevated TG level in any lipid subfraction
      even though there was some reduction in apo C-III levels in VLDL; (2) reductions
      in levels of VLDL and IDL apo B but increases in LDL apo B; (3) increases in HDL
      apo C-III and FC concentrations despite an increase in LCAT activity; and (4)
      increases in apo A-I levels in HDL-L and HDL-M. The addition of a pancreas to a
      kidney transplant had no obvious impact on the lipoproteins.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8139483
TI  - Phenobarbital treatment enhances insulin-mediated glucose metabolism and improves
      lipid metabolism in the diabetic rat.
AB  - Previous studies with healthy volunteers and non-insulin-dependent diabetic
      (NIDDM) patients have shown a strong association between overall glucose
      metabolism and hepatic microsomal enzyme activity. In this study, the effects of
      10-day oral administration of phenobarbital (PB), a potent inducer of the hepatic
      microsomal mixed-function oxidase system, on carbohydrate and lipid metabolism in
      the basal state and on glucose kinetics during submaximal hyperinsulinemic (5
      mU.kg-1.min-1 insulin) clamps were investigated in nondiabetic rats and in rats
      made diabetic by the intravenous (IV) administration of either low-dose (40
      mg/kg) or high-dose (55 mg/kg) streptozocin (STZ). In control rats receiving PB
      in drinking water (0.5 mg/mL), serum insulin and triglyceride levels were
      diminished without any change in glucose and cholesterol concentrations in the
      fed state. Administration of PB in drinking water (0.25 mg/mL) to both groups of
      diabetic rats decreased their water intake and serum triglyceride levels in the
      absence of an effect on glucose, insulin, and cholesterol concentrations in the
      fed state. However, fasting serum glucose levels and basal glucose turnover rates
      were lower in both groups of diabetic rats receiving PB. PB treatment increased
      the heparin-releasable lipoprotein lipase (LPL) activity of epididymal fat in
      both control and low-dose diabetic groups; this was not assessed in the high-dose
      diabetic group. Neither peripheral glucose utilization nor hepatic glucose
      production during submaximal insulin clamps was modified by PB treatment in
      nondiabetic rats. In contrast, PB administration enhanced insulin-mediated
      peripheral glucose utilization, as well as suppression of hepatic glucose
      production, in both low-dose and high-dose diabetic groups.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8139484
TI  - Growth hormone-binding protein levels: studies of children with short stature.
AB  - A high-affinity growth hormone-binding protein (GHBP) in serum is derived from
      the extracellular domain of the GH receptor. In an attempt to investigate the
      differences in GHBP levels in various conditions of poor growth, we measured GHBP
      levels by two methods--an Ultrogel chromatographic technique and a ligand
      mediated immunofunctional assay (LIFA). The following three groups of children
      were studied: Turner's syndrome (n = 7), idiopathic and/or familial short stature
      ([ISS] n = 15), and organic or idiopathic hypopituitarism (n = 19). All groups
      were similar in age (Turner's syndrome, 10.1 +/- 0.9 years; ISS, 10.0 +/- 0.7;
      hypopituitarism, 11.5 +/- 1.0) and height SEM score (Turner's syndrome, -2.9 +/-
      0.3; ISS, -3.0 +/- 0.4; hypopituitarism, -2.3 +/- 0.4). Their values were
      compared with those values of GHBP in healthy controls of similar age.
      Immunofunctional assay values for GHBP were as follows: Turner's syndrome, 235.4
      +/- 26.0 pmol/L; ISS, 122.4 +/- 11.0; and hypopituitarism, 157.1 +/- 23.0. These
      results were significantly different in subjects with ISS and hypopituitarism as
      compared with a group of healthy controls between the ages of 9 and 12 years (N =
      255; GHBP = 287.9 +/- 10.9 pMol/L; P < .001 compared with both ISS and
      hypopituitarism). Similar changes were found using Ultrogel chromatography. This
      difference in GHBP levels is still significant even when more stringent criteria
      are applied to define hypopituitarism (ie, peak GH responses to stimuli < 6.0
      ng/mL, instead of < or = 10 ng/mL originally).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139485
TI  - Quantitative characterization of insulin-glucose response in Watanabe heritable
      hyperlipidemic and cholesterol-fed rabbits and the effect of cilazapril.
AB  - A great deal of evidence suggests that insulin resistance, via hyperinsulinemia,
      contributes to hyperlipoproteinemia and coronary atherosclerosis. When Watanabe
      heritable hyperlipidemic (WHHL) rabbits, an animal model of familial
      hypercholesterolemia (FH), are compared with normolipidemic Japanese White (JW)
      rabbits, an elevated fasting plasma insulin level and a heightened plasma insulin
      response to an intravenous (i.v.) glucose challenge are found. To elucidate the
      mechanism behind this phenomenon, a two-compartment model of the glucose/insulin
      system was fitted to empirical time courses of glucose and insulin concentrations
      during an i.v. glucose tolerance test (IVGTT) by nonlinear least-square
      regression, and the model parameters such as the glucose utilization rate
      constant, insulin degradation rate constant, and pancreas sensitivity were
      determined. WHHL rabbits showed decreased values of glucose utilization and
      insulin degradation rate constants and slightly higher values of pancreas
      sensitivity. This suggests that insulin resistance occurs in extrapancreatic
      tissues, and that this may be attributable to insulin receptor and/or post
      insulin receptor abnormalities. Cholesterol feeding did not significantly change
      glucose tolerance or insulin action in JW rabbits. The effects of an angiotensin
      converting enzyme (ACE) inhibitor, cilazapril, on insulin resistance were also
      examined in WHHL and JW rabbits. A decreased insulin response to an i.v. glucose
      challenge and increased glucose utilization and insulin degradation rate
      constants were observed in WHHL rabbits that had been treated with cilazapril,
      indicating that cilazapril improved insulin resistance in WHHL rabbits, possibly
      by increasing the number of insulin receptors. No significant differences were
      found in glucose tolerance and insulin action in JW rabbits before and after
      cilazapril administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139486
TI  - Beta-cell response and insulin hepatic extraction in noncirrhotic alcoholic
      patients soon after withdrawal.
AB  - A decreased tolerance to carbohydrates has been reported in several studies of
      liver diseases, whereas only a few investigations have been performed in chronic
      noncirrhotic alcoholic patients with and without alcohol abstinence. The aim of
      this study was to evaluate in detail the metabolic portrait of six noncirrhotic
      alcoholics during the early phase of alcohol withdrawal by quantifying the main
      processes involved in glucose disappearance. Data from frequently sampled
      intravenous glucose tolerance tests (FSIGTs) were analyzed by means of the
      minimal model (MINMOD) approach, which provided measurements of the (prehepatic)
      beta-cell secretion and of insulin degradation in the liver, along with indexes
      of insulin sensitivity and glucose effectiveness. Plasma insulin levels were
      lower in the patients (basal, 3.5 +/- 0.2 v 8.0 +/- 1.8 in matching controls, P <
      .05; area under the curve, 1.41 +/- 0.07 mU/mL in 240 minutes v 4.06 +/- 0.37, P
      < .001), and C-peptide concentrations were higher (basal, 107 +/- 3.5 v 36 +/- 9
      ng/dL in controls, P < .05; area under the curve, 492 +/- 118 ng/mL in 240
      minutes v 245 +/- 66, P = .05). The model analysis confirmed the absence of a
      decrease beta-cell release; in fact, in the alcoholics there was a basal
      secretion of 19 +/- 5 versus 9 +/- 2 pmol/L/min in controls (P < .05) and a total
      release of 9.5 +/- 1.8 nmol/L in 240 minutes versus 6.5 +/- 1.4.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8139487
TI  - Dynamics of 24-hour pulsatile cortisol, 17-hydroxyprogesterone, and
      androstenedione release in prepubertal patients with nonclassic 21-hydroxylase
      deficiency and normal prepubertal children.
AB  - To assess whether the quantitative and qualitative aspects of cortisol, 17
      hydroxyprogesterone (17-OHP), and androstenedione (D4A) secretion in patients
      with nonclassic congenital adrenal hyperplasia (NCCAH) differ from those in
      normal children, 24-hour serum concentrations of these steroids were measured in
      five prepubertal patients with NCCAH and five normal prepubertal children.
      Adrenal steroid profiles obtained by 30-minute sampling were analyzed by the
      Pulsar program. In comparison to normal children, the 24-hour quantitative
      parameters of 17-OHP and D4A secretion were significantly greater in NCCAH
      patients, but serum cortisol concentrations were similar in the two groups. When
      daytime and nighttime hormone releases were separately analyzed, a significant
      nocturnal elevation of the cortisol area under the curve above zero level (AUCo)
      and 12-hour mean and 17-OHP AUCo, AUC above baseline, mean peak height,
      amplitude, area, and 12-hour mean was detected in normal subjects only.
      Conversely, NCCAH patients exhibited an increased frequency and number of 17-OHP
      secretory peaks at night together with a reduction of the interpeak interval. No
      significant day/night differences in D4A concentrations were detected either in
      normals or in the patients. In conclusion, the results of the present study
      indicate that patients with NCCAH have a distinct pattern of adrenal steroid
      secretion characterized by a high-frequency 17-OHP release accompanied by a
      relative nocturnal cortisol deficiency.

PMID- 8139488
TI  - Leucine kinetics during a brief fast in diabetes in pregnancy.
AB  - The effect of diabetes in pregnancy on leucine turnover and oxidation was
      examined in 12 insulin-dependent diabetic (IDDM) subjects and 12 gestationally
      diabetic (GDM) subjects during the third trimester of pregnancy. The data were
      compared with those in normal pregnant women studied during the same time period
      and reported previously. Eight of the IDDM subjects were on continuous
      subcutaneous insulin infusion (insulin pump), and four were on conventional twice
      daily insulin treatment. Of the GDM group, seven were on insulin therapy and five
      were on dietary management. Leucine kinetics were quantified using [1-13C]leucine
      tracer in combination with respiratory calorimetry and measurement of lean body
      mass using the H2[18O] dilution method. In addition, glucose kinetics were
      measured in insulin-treated subjects using [6,6(2)H2]glucose tracer. Despite
      rigorous metabolic control, fasting plasma glucose (IDDM 5.5 +/- 1.9 mmol/L [P <
      .05], GDM 4.7 +/- 1.3 [P < .01], controls 3.6 +/- .6, mean +/- SD) and hemoglobin
      A1 ([HbA1] IDDM 7.9 +/- 1.9%, GDM 7.5% +/- 2.1%) levels were higher in diabetic
      subjects. Although total insulin levels were higher in insulin-treated diabetic
      subjects, free-insulin concentrations were similar in all groups. Rates of
      excretion of urinary urea nitrogen and respiratory quotients were also similar.
      The rate of glucose turnover was lower in insulin-treated subjects compared with
      normals. Leucine flux, a measure of the rate of protein breakdown, and leucine
      oxidation were higher in IDDM and insulin-treated GDM subjects. The rate of
      leucine oxidation was increased in conventionally managed IDDM and insulin
      treated GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139489
TI  - Insulin production following intravenous glucose, arginine, and valine: different
      pattern in patients with impaired glucose tolerance and non-insulin-dependent
      diabetes mellitus.
AB  - To better understand abnormal insulin production (IP) in states of carbohydrate
      intolerance, insulin release was quantified following equimolar (2.4 mmol/kg)
      infusions of glucose, arginine, and valine in healthy subjects ([HS] age, 45 +/-
      3 years; body mass index [BMI, kg/m2], 26.3 +/- 2.4; means +/- SEM), obese
      subjects with impaired glucose tolerance ([IGT] age, 43 +/- 5 years; BMI, 35.4 +/
      2.4), and non-obese patients with chronic non-insulin-dependent diabetes
      mellitus ([NIDDM] age, 55 +/- 3 years; BMI, 26.4 +/- 1.4; duration of disease, 13
      +/- 3 years). There were eight subjects per group. Incremental IP (metabolic
      clearance rate of C-peptide [MCRCP] x total incremental area under the curve of
      plasma C-peptide [AUCCP], pmol/kg) following substrate infusion was as follows:
      glucose: HS, 227 +/- 14; IGT, 1,050 +/- 184 (P < .001 v HS); NIDDM, 114 +/- 27 (P
      < .001 v HS); arginine: HS, 139 +/- 23; IGT, 488 +/- 106 (P < .01 v HS); NIDDM,
      206 +/- 47; and valine: HS, 21 +/- 7; IGT, 32 +/- 10; NIDDM, 54 +/- 12 (P < .01 v
      HS). The fractional clearance rate ([FCR] k, %/min) was impaired in IGT and NIDDM
      for glucose (HS, 3.9 +/- 0.4; IGT, 2.3 +/- 0.3 [P < .01 v HS]; NIDDM, 1.4 +/- 0.1
      [P < .001 v HS]), arginine (2.4 +/- 0.1; 1.9 +/- 0.2 [P < .01 v HS]; 1.9 +/- 0.2
      [P < .01 v HS]), and valine (0.95 +/- 0.06; 0.65 +/- 0.09 [P < .05 v HS]; 0.74 +/
      0.1 [P < .05 v HS]).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139490
TI  - Interrelationships between intraabdominal fat and total serum testosterone levels
      in obese women.
AB  - Thirty-six women aged 18 to 52 years with body mass indexes (BMIs) between 27 and
      52 were studied. Visceral and subcutaneous fat areas and body fat were evaluated
      by computerized tomography with a single scan at the IV-V lumbar vertebra level.
      Glucose, insulin, and C-peptide levels were measured before and after a glucose
      load. Total and free serum testosterone and 24-hour urinary cortisol excretion
      were measured. A stepwise multiple regression equation showed the visceral to
      subcutaneous fat area ratio to be the most powerful predictor for glucose
      alterations both during fasting and after a glucose load, and showed BMI to be
      the most powerful predictor for insulin and C-peptide levels. Total serum
      testosterone, after matching for age and BMI, demonstrates a significant negative
      correlation with visceral fat area. We conclude that in obese women, as in men,
      intraabdominal fat negatively correlates with serum testosterone levels.

PMID- 8139491
TI  - Carbohydrate composition analysis of glycoconjugates by gas-liquid
      chromatography/mass spectrometry.

PMID- 8139492
TI  - Mass spectrometry of carbohydrate-containing biopolymers.

PMID- 8139493
TI  - 1H nuclear magnetic resonance spectroscopy of carbohydrate chains of
      glycoproteins.

PMID- 8139494
TI  - Metabolic radiolabeling of glycoconjugates.

PMID- 8139495
TI  - Determination of sialic acids.

PMID- 8139496
TI  - Size fractionation of oligosaccharides.

PMID- 8139497
TI  - High-pH anion-exchange chromatography of glycoprotein-derived carbohydrates.

PMID- 8139498
TI  - High-performance liquid chromatography of pyridylaminated saccharides.

PMID- 8139499
TI  - High-performance liquid chromatography of oligosaccharides.

PMID- 8139500
TI  - High-resolution polyacrylamide gel electrophoresis of fluorophore-labeled
      reducing saccharides.

PMID- 8139501
TI  - Capillary electrophoresis of oligosaccharides.

PMID- 8139502
TI  - Glycosidases in structural analysis.

PMID- 8139503
TI  - Glycosyltransferases in glycobiology.

PMID- 8139504
TI  - Glycosidase inhibitors in study of glycoconjugates.

PMID- 8139505
TI  - Nonmetabolic radiolabeling and tagging of glycoconjugates.

PMID- 8139506
TI  - Synthesis and uses of azido-substituted nucleoside diphosphate sugar
      photoaffinity analogs.

PMID- 8139507
TI  - Glycoform analysis of glycoproteins.

PMID- 8139508
TI  - Isolation of glycosphingolipids.

PMID- 8139509
TI  - Isolation and characterization of proteoglycans.

PMID- 8139510
TI  - Structural analysis of glycosylphosphatidylinositol anchors.

PMID- 8139511
TI  - Enzymatic deglycosylation of asparagine-linked glycans: purification, properties,
      and specificity of oligosaccharide-cleaving enzymes from Flavobacterium
      meningosepticum.

PMID- 8139512
TI  - Detection of O-linked N-acetylglucosamine (O-GlcNAc) on cytoplasmic and nuclear
      proteins.

PMID- 8139513
TI  - Identification of polysialic acids in glycoconjugates.

PMID- 8139514
TI  - Neoglycolipids: probes of oligosaccharide structure, antigenicity, and function.

PMID- 8139515
TI  - Release of oligosaccharides from glycoproteins by hydrazinolysis.

PMID- 8139516
TI  - Use of lectins in analysis of glycoconjugates.

PMID- 8139517
TI  - Saccharide linkage analysis using methylation and other techniques.

PMID- 8139518
TI  - Thermoregulation in neonates.
AB  - Thermoregulation is a critical physiologic function that is closely related to
      the transition and survival of the infant. An understanding of transitional
      events and the physiologic adaptations that neonates must make is essential to
      helping the nurse provide an appropriate environment and help infants maintain
      thermal stability. This article reviews neonatal thermal regulation, heat loss
      and gain, and the thermal response that is generated when thermal stability is
      threatened.

PMID- 8139519
TI  - Caloric loss from expressed mother's milk during continuous gavage infusion.
AB  - Expressed mother's milk (EMM) provides innumerable immunologic and nutritional
      benefits. However, the nutritional value of EMM, especially the calorie-rich
      lipids, may be reduced during continuous gavage infusion (CGI). The purpose of
      the study was to compare the differences in lipid loss of EMM for two types of
      CGI tubing: standard bore and minibore. In an experimental design, 30 specimens
      of EMM were infused using a simulated CGI apparatus with a syringe pump; each of
      the 30 specimens was aliquotted to infuse through both types of CGI tubing.
      Preinfusion and postinfusion lipid concentrations were measured by the
      creamatocrit technique. The mean preinfusion creamatocrit value was 6.57 percent
      (SD = 2.09) with minimum and maximum values of 3.41 and 10.72 percent
      respectively (mean caloric content of 22.91 Kcal/oz). The mean postinfusion
      creamatocrit for standard bore tubing was 4.98 percent (SD = 1.59), with minimum
      and maximum values of 1.90 and 9.38 percent respectively (mean caloric content =
      20.14 Kcal/oz). Mean percent of decrease in lipid concentration between
      preinfusion and postinfusion values for standard bore tubing was 1.59 percent (SD
      = 1.10) (mean caloric loss 2.77 Kcal/oz). The mean postinfusion creamatocrit
      value for the minibore tubing was 5.24 percent (SD = 1.77) with minimum and
      maximum values of 2.55 and 9.68 percent respectively. This equates to a mean
      caloric content of 20.59 Kcal/oz. Mean percent of decrease in lipid concentration
      between preinfusion and postinfusion values for minibore tubing was 1.34 percent
      (SD = 1.02) (mean caloric loss of 2.32 Kcal/oz).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139520
TI  - Theophylline misadventures: Part I.
AB  - Theophylline intoxication has become an important clinical problem in the NICU,
      in large part because of its increased and extensive use for treatment of
      neonatal respiratory diseases. This article reviews the mechanisms of action
      involved in current methylxanthine uses, outlines the range of dosage
      recommendations and target plasma levels in the neonate, describes reported
      toxicities as extensions of the pharmacologic effects, summarizes some recent
      litigation reports addressing theophylline toxicity, and shares recommendations
      from practitioners who have written about the clinical use of this class over the
      past 50 years. By using suitable initial dosing guidelines and aggressive early
      serum concentration monitoring, practitioners can use theophylline safely and
      effectively in neonates.

PMID- 8139521
TI  - Maternal perception of illness severity in premature infants.
AB  - This study examines relationships between the actual severity of the premature
      infant's medical condition, maternal perception of the severity of the infant's
      illness, the infant's birth weight, and maternal anxiety levels. Subjects for
      this study were 44 mothers who were part of a larger study of parental stress in
      neonatal intensive care units (NICUs). The premature infants of these mothers
      were hospitalized in the NICU of a large southeastern university medical center
      at the time of data collection. Mothers completed a severity perception scale and
      the State-Trait Anxiety Inventory. Data about actual severity of each infant's
      illness and about the infant's characteristics were collected from the medical
      chart. The findings indicate that maternal perceptions regarding the severity of
      their premature infants' illness are complex and are influenced by different
      factors at different points in time. A significant relationship was not found
      between the mother's recollection of infant severity at NICU admission and
      maternal perceptions at the time of the interview, two to five days after
      admission. Although maternal recall of the severity of the infant's illness on
      admission is not related to anxiety, perceptions of severity at the time of the
      interview (two to five days after admission) are related to anxiety scores.

PMID- 8139522
TI  - Changes in a changing environment.

PMID- 8139523
TI  - Cardiac monitoring in the neonatal intensive care unit: an evaluation of
      electrodes.
AB  - Two types of electrodes were evaluated over a six-week period in a neonatal
      intensive care nursery. Babies requiring monitoring were alternately assigned to
      either of two groups: Klear-Trace (n = 37) or Sentry (n = 51). Nursing staff
      monitored a range of variables daily. Klear-Trace electrodes, although slightly
      more expensive, lasted significantly longer than Sentry electrodes (p > .0001).
      Factors such as incubator temperature and the weight of the neonate did not
      affect results, nor was there any difference in the frequency of repositioning
      electrodes between the two products. Because Klear-Trace electrodes last three
      times as long as Sentry electrodes (six days as opposed to two days), there may
      be cost advantages in using Klear-Trace electrodes.

PMID- 8139524
TI  - Pulmonary function testing in the critically ill neonate, Part II: Methodology.
AB  - Pulmonary function testing is an important diagnostic tool in neonatal intensive
      care. These tests provide a detailed assessment of an infant's pulmonary status
      that can be used in several ways: to monitor the progression of lung disease, to
      streamline ventilator management, and to assess the infant's response to new
      treatments, such as surfactant replacement therapy or bronchodilators. In some
      settings, these tests are performed by specially trained nurses, and the results
      are available immediately for planning nursing care. This relatively noninvasive
      and low-risk assessment can be performed on all infants, whether on mechanical
      ventilation or breathing spontaneously. A comprehensive pulmonary function
      evaluation can be performed at the bedside in less than 60 minutes and is
      generally well tolerated. In this article, the determination of pulmonary "vital
      signs" tidal volume, minute ventilation, respiratory rate, pulmonary compliance,
      resistance, resistive work of breathing, and functional residual capacity-are
      discussed. The esophageal balloon technique for measuring dynamic pulmonary
      mechanics and energetics, as well as the helium dilution technique for measuring
      functional residual capacity, are described.

PMID- 8139525
TI  - Surveillance for pregnancy and birth rates among teenagers, by state--United
      States, 1980 and 1990.
AB  - PROBLEM/CONDITION: In the United States in 1990, there were an estimated 1
      million pregnancies and 521,826 births among women ages 15-19 years. Rates of
      teenage pregnancy and birth rates by state in 1990 exceeded those in most
      developed countries. An estimated 95% of teenage pregnancies are unintended
      (i.e., they occur sooner than desired or are not wanted at any time). REPORTING
      PERIOD COVERED: This report summarizes and reviews surveillance data for
      pregnancies, abortions, and births among women ages 15-19, 15-17, and 18-19 years
      reported by CDC for 1980 and 1990. DESCRIPTION OF SYSTEM: Data for births and
      abortions were reported to state health departments and other health agencies and
      sent to CDC. The data from each state included the total number of births and
      abortions by age and race/ethnicity. RESULTS: Data in this report indicate that
      pregnancy rates by state among U.S. teenagers ages 15-19 years have changed
      little since 1980. Moreover, many states have reported increases in birth rates
      that are probably related to concurrent decreases in abortion rates. Pregnancy
      rates range from 25 to 75 per 1,000 for 15- to 17-year-olds and from 92 to 165
      per 1,000 for 18- to 19-year-olds. INTERPRETATION: States with low rates of
      teenage pregnancy or birth may have developed and used prevention strategies
      directed at the needs of both younger and older teenagers; these programs may
      serve as models for other states where birth rates have remained high or have
      increased since 1980. ACTIONS TAKEN: CDC will continue to conduct surveillance of
      and analyze data for pregnancies, abortions, and births among teenagers to
      monitor progress toward national goals and to assist in targeting program efforts
      for reducing teenage pregnancy.

PMID- 8139526
TI  - Abortion surveillance--United States, 1990.
AB  - CONDITION: Since 1980, the number of legal induced abortions reported to CDC has
      remained fairly stable, varying each year by < or = 5%. REPORTING PERIOD COVERED:
      This report summarizes and reviews data received by CDC for legal induced
      abortions obtained in 1990. DESCRIPTION OF SYSTEM: For each year, CDC compiles
      abortion data received from 52 reporting areas: 50 states, New York City, and the
      District of Columbia. RESULTS: In 1990, 1,429,577 abortions were reported--a 2.4%
      increase from 1989. The abortion ratio for 1990 was 345 legal induced abortions
      per 1,000 live births, and the abortion rate was 24 per 1,000 women ages 15-44
      years. Most women undergoing abortions were young, white, and unmarried; most had
      had no previous live births and were having the procedure for the first time.
      Approximately half of all abortions were performed before the 8th week of
      gestation, and 87% were before the 13th week of gestation. Younger women were
      more likely to obtain abortions later in pregnancy than were older women.
      INTERPRETATION: Since 1980, the national number (and rate) of abortions has
      remained relatively stable, with only small (< or = 5%) year-to-year
      fluctuations. However, since 1984, the national abortion ratio has declined; in
      1990, the abortion ratio was the lowest recorded since 1977. Increasing rates of
      childbearing may account for some of this decline. ACTIONS TAKEN: The number and
      characteristics of women having abortions are needed from all states to furnish
      an accurate characterization of legal induced abortion in the United States and
      to assist efforts to identify and reduce preventable causes of morbidity and
      mortality associated with abortions.

PMID- 8139527
TI  - Surveillance for geographic and secular trends in congenital syphilis--United
      States, 1983-1991.
AB  - PROBLEM/CONDITION: CDC monitors trends in the occurrence of congenital syphilis
      (CS) in the United States by using surveillance data sent from state and local
      health departments. Comparisons of data from this surveillance system with data
      from the Division of Sexually Transmitted Diseases/HIV Prevention and the Birth
      Defects Monitoring Program (BDMP) can be used to assess the potential effects of
      changes in case finding and reporting practices on these trends. REPORTING PERIOD
      COVERED: This report covers CS surveillance in the United States for the years
      1983-1991. DESCRIPTION OF SYSTEM: Cases of CS among infants < 1 year of age and
      primary and secondary (P&S) syphilis among women are reported quarterly to CDC.
      The BDMP is a CDC national surveillance system that samples hospital discharge
      data on U.S. births. RESULTS: During the period 1983-1991, 12,151 CS cases were
      reported. Before 1988, regional CS incidence increased 35%-131% annually. Larger
      increases occurred in the Northeast (578%) in 1989 and in the South (178%),
      Midwest (244%), and West (777%) in 1990. Within regions, these larger increases
      were temporally related to increases in P&S syphilis in women and changes to a
      more sensitive CS case definition. INTERPRETATION: CS incidence has increased
      since 1983 in all regions of the United States. Increases since 1988 reflect both
      changes in surveillance reporting practices--the surveillance case definition for
      CS was changed in 1988 and further revised in 1989--and a true increase in
      incidence. ACTIONS TAKEN: These data indicate where CS prevention efforts need to
      be targeted. To facilitate reporting of CS cases, CDC has developed a) a shorter
      form for reporting cases of CS after 1991 and b) a software package for use by
      state and local health departments to enter and analyze CS data.

PMID- 8139528
TI  - Surveillance for ectopic pregnancy--United States, 1970-1989.
AB  - PROBLEM/CONDITION: From 1970 through 1989, hospitalizations for ectopic pregnancy
      have increased in the United States; the number of cases has increased fivefold,
      from 17,800 to 88,400. REPORTING PERIOD COVERED: 1970-1989. DESCRIPTION OF
      SYSTEM: Reported ectopic pregnancies were estimated from data collected by CDC's
      National Center for Health Statistics (NCHS) as part of the ongoing National
      Hospital Discharge Survey. Data from responding hospitals were weighted to
      represent national estimates. The number of deaths resulting from ectopic
      pregnancy was based on U.S. vital statistics collected by NCHS. Denominators for
      calculating ectopic pregnancy rates were the total number of reported
      pregnancies, which includes live births, legal induced abortions, and ectopic
      pregnancies. Data for live births were obtained from NCHS natality statistics and
      data for legal induced abortions from CDC's Division of Reproductive Health.
      RESULTS: From 1970 through 1989, more than one million ectopic pregnancies were
      estimated to have occurred among women in the United States; the rate increased
      by almost fourfold, from 4.5 to 16.0 ectopic pregnancies per 1,000 reported
      pregnancies. Although ectopic pregnancies accounted for < 2% of all reported
      pregnancies during this period, complications of this condition were associated
      with approximately 13% of all pregnancy-related deaths. During this period, the
      risk of death associated with ectopic pregnancy decreased by 90%: the case
      fatality rate declined from 35.5 deaths per 10,000 ectopic pregnancies in 1970 to
      3.8 in 1989. The risks of ectopic pregnancy and death from its complications were
      consistently higher for blacks and other racial/ethnic minorities than for whites
      throughout the period. INTERPRETATION: Although the general trend has been for
      the numbers and rates of ectopic pregnancy to increase over the 20-year period,
      the variability of the data does not permit meaningful conclusions to be made
      about year-to-year changes in the estimates of ectopic pregnancies, especially
      for the years 1988 and 1989. ACTIONS TAKEN: These findings indicate the need to
      characterize behaviors and risk factors that may respond to preventive
      interventions. Until these risks factors are better characterized, early
      detection and appropriate management of ectopic pregnancies will remain the most
      effective means of reducing the morbidity and mortality associated with this
      condition.

PMID- 8139529
TI  - Multiple cis-acting targeting sequences are required for orb mRNA localization
      during Drosophila oogenesis.
AB  - The targeting of positional information to specific regions of the oocyte or
      early embryo is one of the key processes in establishing anterior-posterior and
      dorsal-ventral polarity. In many developmental systems, this is accomplished by
      localization of mRNAs. The germ line-specific Drosophila orb gene plays a
      critical role in defining both axes of the developing oocyte, and its mRNA is
      localized in a complex pattern during oogenesis. We have identified a 280-bp
      sequence from the orb 3' untranslated region capable of reproducing this complex
      localization pattern. Furthermore, we have found that multiple cis-acting
      elements appear to be required for proper targeting of orb mRNA.

PMID- 8139530
TI  - Sequences containing the second-intron enhancer are essential for transcription
      of the human apolipoprotein B gene in the livers of transgenic mice.
AB  - To identify DNA sequence elements from the human apolipoprotein B (apoB) gene
      required for high-level, correct tissue-specific expression in transgenic mice,
      we made several constructs that included one or more of the key regulatory
      elements that were previously characterized with cultured liver-derived and
      intestine-derived cell lines. Our data show that the apoB promoter alone (-898 to
      +121) is not sufficient to direct transcription in transgenic mice. An enhancer
      located in the second intron is absolutely required to specify transcription by
      the homologous apoB promoter in the livers of transgenic mice; this enhancer does
      not direct transcription in the small intestines. Thus, the elements controlling
      transcriptional activation of the apoB gene in the liver and the intestine in
      vivo are distinct and separable. Analysis of the DNase I hypersensitivity of the
      integrated human transgenes in various lines of expressing and nonexpressing mice
      suggests that the formation of DH4, a strong hypersensitive site in intron 2, may
      be a prerequisite for hepatic expression of the apoB gene. Nuclear matrix
      association regions (MARs) of the apoB gene may play a role in transgene
      expression. Constructs including MAR sequences displayed higher levels of
      expression than those lacking them. However, these MARs did not completely
      insulate the associated transgenes from position effects.

PMID- 8139531
TI  - A dominant negative erythropoietin (EPO) receptor inhibits EPO-dependent growth
      and blocks F-gp55-dependent transformation.
AB  - The erythropoietin receptor (EPO-R), a member of the cytokine receptor
      superfamily, can be activated to signal cell growth by binding either EPO or F
      gp55, the Friend spleen focus-forming virus glycoprotein. Activation by F-gp55
      results in constitutive EPO-R signalling and the first stage of Friend virus
      induced erythroleukemia. We have generated a truncated form of the EPO-R
      polypeptide [EPO-R(T)] which lacks the critical cytoplasmic signal-transducing
      domain of the EPO-R required for EPO- or F-gp55-induced cell growth. EPO-R(T)
      specifically inhibited the EPO-dependent growth of EPO-R-expressing Ba/F3 cells
      without changing the interleukin-3-dependent growth of these cells. In addition,
      Ba/F3 cells that coexpressed wild-type EPO-R and EPO-R(T) were resistant to
      transformation by F-gp55 despite efficient expression of the F-gp55 transforming
      oncoprotein in infected cells. EPO-R(T) inhibited the EPO-dependent tyrosine
      phosphorylation of wild-type EPO-R, the tyrosine kinase (JAK2), and the SH2
      adaptor protein (Shc). In conclusion, the EPO-R(T) polypeptide is a dominant
      negative polypeptide which specifically interferes with the early stages of EPO-R
      mediated signal transduction and which prevents Friend virus transformation of
      erythroblasts.

PMID- 8139532
TI  - A constitutively activated erythropoietin receptor stimulates proliferation and
      contributes to transformation of multipotent, committed nonerythroid and
      erythroid progenitor cells.
AB  - If the env gene of spleen focus-forming virus (SFFV) is replaced by a cDNA
      encoding a constitutively active form of the erythropoietin receptor, EPO
      R(R129C), the resultant recombinant virus, SFFVcEPO-R, induces transient
      thrombocytosis and erythrocytosis in infected mice. Clonogenic progenitor cell
      assays of cells from the bone marrow and spleens of these infected mice suggest
      that EPO-R(R129C) can stimulate proliferation of committed megakaryocytic and
      erythroid progenitors as well as nonerythroid multipotent progenitors. From the
      spleens of SFFVcEPO-R-infected mice, eight multiphenotypic immortal cell lines
      were isolated and characterized. These included primitive erythroid, lymphoid,
      and monocytic cells. Some expressed proteins characteristic of more than one
      lineage. All cell lines resulting from SFFVcEPO-R infection contained a mutant
      form of the p53 gene. However, in contrast to infection by SFFV, activation of
      PU.1 gene expression, by retroviral integration, was not observed. One cell line
      had integrated a provirus upstream of the fli-1 gene, in a location typically
      seen in erythroleukemic cells generated by Friend murine leukemia virus
      infection. This event led to increased expression of fli-1 in this cell line.
      Thus, infection by SFFVcEPO-R can induce proliferation and lead to transformation
      of nonerythroid as well as very immature erythroid progenitor cells. The sites of
      proviral integration in clonal cell lines are distinct from those in SFFV-derived
      lines.

PMID- 8139533
TI  - Overexpression of C-terminally but not N-terminally truncated Myb induces
      fibrosarcomas: a novel nonhematopoietic target cell for the myb oncogene.
AB  - The myb oncogene encodes a DNA-binding transcriptional transactivator which can
      become a hematopoietic cell-transforming protein following the deletion of amino
      acid sequences from either its amino or carboxyl terminus. Although a number of
      hematopoietic tumors express terminally deleted variants of Myb, the involvement
      of truncated Myb in nonhematopoietic tumors has not been adequately investigated.
      To assess the full spectrum of Myb's oncogenic capability, a replication
      competent retroviral vector (RCAMV) was used to express a full-length protein (C
      Myb), an amino-terminally truncated protein (VCC- or delta N-Myb), a carboxyl
      terminally truncated protein (T-Myb), or a doubly truncated protein (VCT-Myb) in
      vivo. These viruses were injected intravenously into 10-day chicken embryos, and
      the infected chicks were monitored for tumors. Approximately 4 to 8 weeks after
      hatching, the majority (30 of 39 [77%]) of animals infected with the T-Myb
      retrovirus (without 214 carboxyl-terminal residues) developed nodular muscle
      tumors which could be identified by both morphologic and immunohistochemical
      criteria as fibrosarcomas. Identically appearing tumors could also be found in
      the kidney of some T-Myb-infected animals. The T-Myb-induced fibrosarcomas
      expressed the appropriately sized T-Myb protein, contained an unaltered proviral
      T-myb gene, and showed clonal proviral integration sites. In comparison, no
      sarcomas were observed in any of the animals infected with the amino-terminally
      truncated (VCC- and delta N-Myb) or doubly truncated (VCT-Myb) viruses. A loss of
      carboxyl-terminal but not amino-terminal sequences can thus convert Myb into a
      potent in vivo transforming protein for nonhematopoietic mesenchymal cells. In
      comparison, a truncation of either or both ends of the protein can activate Myb
      into a hematopoietic cell-transforming protein.

PMID- 8139534
TI  - A gene involved in control of human cellular senescence on human chromosome 1q.
AB  - Normal cells in culture exhibit limited division potential and have been used as
      a model for cellular senescence. In contrast, tumor-derived or carcinogen- or
      virus-transformed cells are capable of indefinite division. Fusion of normal
      human diploid fibroblasts with immortal human cells yielded hybrids having
      limited life spans, indicating that cellular senescence was dominant. Fusions of
      various immortal human cell lines with each other led to the identification of
      four complementation groups for indefinite division. The purpose of this study
      was to determine whether human chromosome 1 could complement the recessive
      immortal defect of human cell lines assigned to one of the four complementation
      groups. Using microcell fusion, we introduced a single normal human chromosome 1
      into immortal human cell lines representing the complementation groups and
      determined that it caused loss of proliferative potential of an osteosarcoma
      derived cell line (TE85), a cytomegalovirus-transformed lung fibroblast cell line
      (CMV-Mj-HEL-1), and a Ki-ras(+)-transformed derivative of TE85 (143B TK-), all of
      which were assigned to complementation group C. This chromosome 1 caused no
      change in proliferative potential of cell lines representing the other
      complementation groups. A derivative of human chromosome 1 that had lost most of
      the q arm by spontaneous deletion was unable to induce senescence in any of the
      immortal cell lines. This finding indicates that the q arm of human chromosome 1
      carries a gene or set of genes which is altered in the cell lines assigned to
      complementation group C and is involved in the control of cellular senescence.

PMID- 8139535
TI  - Subcellular locations of MOD5 proteins: mapping of sequences sufficient for
      targeting to mitochondria and demonstration that mitochondrial and nuclear
      isoforms commingle in the cytosol.
AB  - MOD5, a gene responsible for the modification of A37 to isopentenyl A37 of both
      cytosolic and mitochondrial tRNAs, encodes two isozymes. Initiation of
      translation at the first AUG of the MOD5 open reading frame generates delta 2
      isopentenyl pyrophosphate:tRNA isopentanyl transferase I (IPPT-I), which is
      located predominantly, but not exclusively, in the mitochondria. Initiation of
      translation at a second AUG generates IPPT-II, which modifies cytoplasmic tRNA.
      IPPT-II is unable to target to mitochondria. The N-terminal sequence present in
      IPPT-I and absent in IPPT-II is therefore necessary for mitochondrial targeting.
      In these studies, we fused MOD5 sequences encoding N-terminal regions to genes
      encoding passenger proteins, pseudomature COXIV and dihydrofolate reductase, and
      studied the ability of these chimeric proteins to be imported into mitochondria
      both in vivo and in vitro. We found that the sequences necessary for
      mitochondrial import, amino acids 1 to 11, are not sufficient for efficient
      mitochondrial targeting and that at least some of the amino acids shared by IPPT
      I and IPPT-II comprise part of the mitochondrial targeting information. We used
      indirect immunofluorescence and cell fractionation to locate the MOD5 isozymes in
      yeast. IPPT-I was found in two subcellular compartments: mitochondria and the
      cytosol. We also found that IPPT-II had two subcellular locations: nuclei and the
      cytosol. The nuclear location of this protein is surprising because the A37-
      >isopentenyl A37 modification had been predicted to occur in the cytoplasm. MOD5
      is one of the first genes reported to encode isozymes found in three subcellular
      compartments.

PMID- 8139537
TI  - A nuclear encoded tRNA of Trypanosoma brucei is imported into mitochondria.
AB  - The mitochondrial genome of trypanosomes, unlike that of most other eukaryotes,
      does not appear to encode any tRNAs. Therefore, mitochondrial tRNAs must be
      either imported into the organelle or created through a novel mitochondrial
      process, such as RNA editing. Trypanosomal tRNA(Tyr), whose gene contains an 11
      nucleotide intron, is present in both the cytosol and the mitochondrion and is
      encoded by a single-copy nuclear gene. By site-directed mutagenesis, point
      mutations were introduced into this tRNA gene, and the mutated gene was
      reintroduced into the trypanosomal nuclear genome by DNA transfection. Expression
      of the mutant tRNA led to the accumulation of unspliced tRNA(Tyr) (A. Schneider,
      K. P. McNally, and N. Agabian, J. Biol. Chem. 268:21868-21874, 1993). Cell
      fractionation revealed that a significant portion of the unspliced mutant
      tRNA(Tyr) was recovered in the mitochondrial fraction and was resistant to
      micrococcal nuclease treatment in the intact organelle. Expression of the nuclear
      integrated, mutated tRNA gene and recovery of its gene product in the
      mitochondrial fraction directly demonstrated import. In vitro experiments showed
      that the unspliced mutant tRNA(Tyr), in contrast to the spliced wild-type form,
      was no longer a substrate for the cognate aminoacyl synthetase. The presence of
      uncharged tRNA in the mitochondria demonstrated that aminoacylation was not
      coupled to import.

PMID- 8139536
TI  - The translation initiation factor eIF-4B contains an RNA-binding region that is
      distinct and independent from its ribonucleoprotein consensus sequence.
AB  - eIF-4B is a eukaryotic translation initiation factor that is required for the
      binding of ribosomes to mRNAs and the stimulation of the helicase activity of eIF
      4A. It is an RNA-binding protein that contains a ribonucleoprotein consensus
      sequence (RNP-CS)/RNA recognition motif (RRM). We examined the effects of
      deletions and point mutations on the ability of eIF-4B to bind a random RNA, to
      cooperate with eIF-4A in RNA binding, and to enhance the helicase activity of eIF
      4A. We report here that the RNP-CS/RRM alone is not sufficient for eIF-4B binding
      to RNA and that an RNA-binding region, located between amino acids 367 and 423,
      is the major contributor to RNA binding. Deletions which remove this region
      abolish the ability of eIF-4B to cooperate with eIF-4A in RNA binding and the
      ability to stimulate the helicase activity of eIF-4A. Point mutations in the RNP
      CS/RRM had no effect on the ability of eIF-4B to cooperate with eIF-4A in RNA
      binding but significantly reduced the stimulation of eIF-4A helicase activity.
      Our results indicate that the carboxy-terminal RNA-binding region of eIF-4B is
      essential for eIF-4B function and is distinct from the RNP-CS/RRM.

PMID- 8139538
TI  - Distinct binding determinants for 9-cis retinoic acid are located within AF-2 of
      retinoic acid receptor alpha.
AB  - Retinoids exert their physiological action by interacting with two families of
      nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X
      receptors (RXRs), which regulate gene expression by forming transcriptionally
      active heterodimeric RAR/RXR or homodimeric RXR/RXR complexes on DNA. Retinoid
      receptor activity resides in several regions, including the DNA and ligand
      binding domains, a dimerization interface, and both a ligand-independent (AF-1)
      and a ligand-dependent (AF-2) transactivation function. While 9-cis retinoic acid
      (RA) alone is the cognate ligand for the RXRs, both 9-cis RA and all-trans RA (t
      RA) compete for binding with high affinity to the RARs. This latter observation
      suggested to us that the two isomers may interact with a common binding site.
      Here we report that RAR alpha has two distinct but overlapping binding sites for
      9-cis RA and t-RA. Truncation of a human RAR alpha to 419 amino acids yields a
      receptor that binds both t-RA and 9-cis RA with high affinity, but truncation to
      amino acid 404 yields a mutant receptor that binds only t-RA with high affinity.
      Remarkably, this region also defines a C-terminal boundary for AF-2, as addition
      of amino acids 405 to 419 restores receptor-mediated gene activity to a truncated
      human RAR alpha lacking this region. It is interesting to speculate that binding
      of retinoid stereoisomers to unique sites within an RAR may function with AF-2 to
      cause differential activation of retinoid-responsive gene pathways.

PMID- 8139539
TI  - Acetylcholine muscarinic m1 receptor regulation of cyclic AMP synthesis controls
      growth factor stimulation of Raf activity.
AB  - Acetylcholine muscarinic m2 receptors (m2R) couple to heterotrimeric Gi proteins
      and activate the Ras/Raf/mitogen-activated protein kinase pathway and
      phosphatidylinositol 3-kinase in Rat 1a cells. In contrast to the m2R,
      stimulation of the acetylcholine muscarinic m1 receptor (m1R) does not activate
      the Ras/Raf/mitogen-activated protein kinase regulatory pathway in Rat 1a cells
      but rather causes a pronounced inhibition of epidermal growth factor and platelet
      derived growth factor receptor activation of Raf. In Rat 1a cells, m1R
      stimulation of phospholipase C beta and the marked rise in intracellular calcium
      stimulated cyclic AMP (cAMP) synthesis, resulting in the activation of protein
      kinase A. Stimulation of protein kinase A inhibited Raf activation in response to
      growth factors. Platelet-derived growth factor receptor stimulation of
      phosphatidylinositol 3-kinase activity was not affected by either m1R stimulation
      or protein kinase A activation in response to forskolin-stimulated cAMP
      synthesis. GTP loading of Ras in response to growth factors was unaffected by
      protein kinase A activation but was partially inhibited by carbachol stimulation
      of the m1R. Therefore, protein kinase A action at the Ras/Raf activation
      interface selectively inhibited only one branch of the signal transduction
      network initiated by tyrosine kinases. Specific adenylyl cyclases responding to
      different signals, including calcium, with enhanced cAMP synthesis will regulate
      Raf activation in response to Ras.GTP. Taken together, the data indicate that G
      protein-coupled receptors can positively and negatively regulate the
      responsiveness of tyrosine kinase-stimulated mitogenic response pathways.

PMID- 8139541
TI  - The gadd and MyD genes define a novel set of mammalian genes encoding acidic
      proteins that synergistically suppress cell growth.
AB  - A remarkable overlap was observed between the gadd genes, a group of often
      coordinately expressed genes that are induced by genotoxic stress and certain
      other growth arrest signals, and the MyD genes, a set of myeloid differentiation
      primary response genes. The MyD116 gene was found to be the murine homolog of the
      hamster gadd34 gene, whereas MyD118 and gadd45 were found to represent two
      separate but closely related genes. Furthermore, gadd34/MyD116, gadd45, MyD118,
      and gadd153 encode acidic proteins with very similar and unusual charge
      characteristics; both this property and a similar pattern of induction are shared
      with mdm2, whic, like gadd45, has been shown previously to be regulated by the
      tumor suppressor p53. Expression analysis revealed that they are distinguished
      from other growth arrest genes in that they are DNA damage inducible and suggest
      a role for these genes in growth arrest and apoptosis either coupled with or
      uncoupled from terminal differentiation. Evidence is also presented for
      coordinate induction in vivo by stress. The use of a short-term transfection
      assay, in which expression vectors for one or a combination of these gadd/MyD
      genes were transfected with a selectable marker into several different human
      tumor cell lines, provided direct evidence for the growth-inhibitory functions of
      the products of these genes and their ability to synergistically suppress growth.
      Taken together, these observations indicate that these genes define a novel class
      of mammalian genes encoding acidic proteins involved in the control of cellular
      growth.

PMID- 8139540
TI  - The novel primary response gene MyD118 and the proto-oncogenes myb, myc, and bcl
      2 modulate transforming growth factor beta 1-induced apoptosis of myeloid
      leukemia cells.
AB  - Cell numbers are regulated by a balance among proliferation, growth arrest, and
      programmed cell death. A profound example of cell homeostasis, controlled
      throughout life, is the complex process of blood cell development, yet little is
      understood about the intracellular mechanisms that regulate blood cell growth
      arrest and programmed cell death. In this work, using transforming growth factor
      beta 1 (TGF beta 1)-treated M1 myeloid leukemia cells and genetically engineered
      M1 cell variants, the regulation of growth arrest and apoptosis was dissected.
      Blocking of early expression of MyD118, a novel differentiation primary response
      gene also shown to be a primary response gene induced by TGF beta 1, delayed TGF
      beta 1-induced apoptosis, demonstrating that MyD118 is a positive modulator of
      TGF beta 1-mediated cell death. Elevated expression of bcl-2 blocked the TGF beta
      1-induced apoptotic pathway but not growth arrest induced by TGF beta 1.
      Deregulated expression of either c-myc or c-myb inhibited growth arrest and
      accelerated apoptosis, demonstrating for the first time that c-myb plays a role
      in regulating apoptosis. In all cases, the apoptotic response was correlated with
      the level of MyD118 expression. Taken together, these findings demonstrate that
      the primary response gene MyD118 and the c-myc, c-myb, and bcl-2 proto-oncogenes
      interact to modulate growth arrest and apoptosis of myeloid cells.

PMID- 8139542
TI  - A segment of mRNA encoding the leader peptide of the CPA1 gene confers repression
      by arginine on a heterologous yeast gene transcript.
AB  - The expression of the yeast gene CPA1, which encodes the small subunit of the
      arginine pathway carbamoylphosphate synthetase, is repressed by arginine at a
      translational level. CPA1 mRNA contains a 250-nucleotide-long leader which
      includes a 25-codon upstream open reading frame (uORF). Oligonucleotide site
      directed mutagenesis of this uORF as well as sequencing of constitutive cis
      dominant mutations has suggested that the leader peptide product of the CPA1 uORF
      is an essential negative element for repression of the CPA1 gene by arginine. In
      this work, a series of deletions affecting the regions 5' and 3' to the uORF in
      the leader sequence was constructed. The arginine-dependent repression of CPA1
      was little affected in these constructions, indicating that these regions are not
      essential for the regulatory response. This conclusion was further supported by
      the finding that inserting the mRNA segment encoding the leader peptide sequence
      of CPA1 in the leader sequence of another gene, namely, GCN4, places this gene
      under arginine repression. Similarly, the behavior of fusions of the leader
      sequence of CPA1 with those of ARG4 or GAL10 confirmed that the regions of this
      leader located upstream and downstream from the uORF are dispensable for the
      regulation by arginine. Finally, a set of substitution mutations which modify the
      uORF nucleotide sequence while leaving unchanged the corresponding amino acid
      sequence was constructed. The mutations did not affect the repression of CPA1 by
      arginine. The data presented in this paper consequently agree with the conclusion
      that the leader peptide itself is the main element required for the translational
      repression of CPA1.

PMID- 8139544
TI  - Targeting frequency for deletion vectors in embryonic stem cells.
AB  - We analyzed the gene targeting frequencies and recombination products generated
      by a series of replacement deletion vectors which target the hprt (hypoxanthine
      phosphoribosyltransferase) locus in mouse embryonic stem cells. We found that the
      targeting frequency of a 19.2-kb deletion was comparable to that of a 3-kb
      deletion or a conventional replacement event in which a 1.7-kb fragment was
      inserted into the locus. We also observed different integration patterns for
      these deletion vectors. A result of this finding is that a wide range of genomic
      deletions in embryonic stem cells is feasible.

PMID- 8139543
TI  - NHP6A and NHP6B, which encode HMG1-like proteins, are candidates for downstream
      components of the yeast SLT2 mitogen-activated protein kinase pathway.
AB  - The yeast SLK1 (BCK1) gene encodes a mitogen-activated protein kinase (MAPK)
      activator protein which functions upstream in a protein kinase cascade that
      converges on the MAPK Slt2p (Mpk1p). Dominant alleles of SLK1 have been shown to
      bypass the conditional lethality of a protein kinase C mutation, pkc1-delta,
      suggesting that Pkc1p may regulate Slk1p function. Slk1p has an important role in
      morphogenesis and growth control, and deletions of the SLK1 gene are lethal in a
      spa2-delta mutant background. To search for genes that interact with the SLK1
      SLT2 pathway, a synthetic lethal suppression screen was carried out. Genes which
      in multiple copies suppress the synthetic lethality of slk1-1 spa2-delta were
      identified, and one, the NHP6A gene, has been extensively characterized. The
      NHP6A gene and the closely related NHP6B gene were shown previously to encode
      HMG1-like chromatin-associated proteins. We demonstrate here that these genes are
      functionally redundant and that multiple copies of either NHP6A or NHP6B suppress
      slk1-delta and slt2-delta. Strains from which both NHP6 genes were deleted (nhp6
      delta mutants) share many phenotypes with pkc1-delta, slk1-delta, and slt2-delta
      mutants. nhp6-delta cells display a temperature-sensitive growth defect that is
      rescued by the addition of 1 M sorbitol to the medium, and they are sensitive to
      starvation. nhp6-delta strains also exhibit a variety of morphological and
      cytoskeletal defects. At the restrictive temperature for growth, nhp6-delta
      mutant cells contain elongated buds and enlarged necks. Many cells have patches
      of chitin staining on their cell surfaces, and chitin deposition is enhanced at
      the necks of budded cells. nhp6-delta cells display a defect in actin polarity
      and often accumulate large actin chunks. Genetic and phenotypic analysis
      indicates that NHP6A and NHP6B function downstream of SLT2. Our results indicate
      that the Slt2p MAPK pathway in Saccharomyces cerevisiae may mediate its function
      in cell growth and morphogenesis, at least in part, through high-mobility group
      proteins.

PMID- 8139545
TI  - Efficient and sustained gene expression in primary T lymphocytes and primary and
      cultured tumor cells mediated by adeno-associated virus plasmid DNA complexed to
      cationic liposomes.
AB  - We have used cationic liposomes to facilitate adeno-associated virus (AAV)
      plasmid transfections of primary and cultured cell types. AAV plasmid DNA
      complexed with liposomes showed levels of expression several fold higher than
      those of complexes with standard plasmids. In addition, long-term expression (>
      30 days) of the gene, unlike the transient expression demonstrated by typical
      liposome-mediated transfection with standard plasmids, was observed. Southern
      analysis of chromosomal DNA further substantiated the hypothesis that the long
      term expression was due to the presence of the transgene in the AAV plasmid
      transfected group and not in the standard plasmid-transfected group. AAV plasmid
      liposome complexes induced levels of transgene expression comparable to those
      obtained by recombinant AAV transduction. Primary breast, ovarian, and lung tumor
      cells were transfectable with the AAV plasmid DNA-liposome complexes. Transfected
      primary and cultured tumor cells were able to express transgene product even
      after lethal irradiation. High-level gene expression was also observed in freshly
      isolated CD3+, CD4+, and CD8+ T cells from normal human peripheral blood.
      Transfection efficiency ranged from 10 to 50% as assessed by intracellular
      interleukin-2 levels in interleukin-2-transfected cells. The ability to express
      transgenes in primary tumor and lymphoid cells may be applied toward tumor
      vaccine studies and protocols which may eventually permit highly specific
      modulation of the cellular immune response in cancer and AIDS.

PMID- 8139546
TI  - Oncogenic activation of the Lck protein accompanies translocation of the LCK gene
      in the human HSB2 T-cell leukemia.
AB  - The tyrosine protein kinase p56lck transduces signals important for antigen
      induced T-cell activation. In transgenic mice, p56lck is oncogenic when
      overexpressed or expressed as a mutant, catalytically activated enzyme. In
      humans, the LCK gene is located at the breakpoint of the t(1;7)(p34;q34)
      chromosomal translocation. This translocation positions the beta T-cell receptor
      constant region enhancer upstream of the LCK gene without interrupting the LCK
      coding sequences, and a translocation of this sort occurs in both the HSB2 and
      the SUP-T-12 T-cell lines. We have found that, although the level of the p56lck
      protein in HSB2 cells is elevated approximately 2-fold in comparison with that in
      normal T-cell lines, total cellular tyrosine protein phosphorylation is elevated
      approximately 10-fold. Increased levels of phosphotyrosine in HSB2 cells resulted
      from mutations in the LCK gene that activated its function as a
      phosphotransferase and converted it into a dominant transforming oncogene. The
      oncogenic p56lck in HSB2 cells contained one amino acid substitution within the
      CD4/CD8-binding domain, two substitutions in the kinase domain, and an insertion
      of Gln-Lys-Pro (QKP) between the SH2 and kinase domains. In NIH 3T3 fibroblasts,
      three of these mutations cooperated to produce the fully oncogenic form of this
      p56lck variant. These results suggest that mutation of LCK may contribute to some
      human T-cell leukemias.

PMID- 8139547
TI  - A cellular factor stimulates ligand-dependent release of hsp90 from the basic
      helix-loop-helix dioxin receptor.
AB  - In response to dioxin, the nuclear basic helix-loop-helix (bHLH) dioxin receptor
      forms a complex with the bHLH partner factor Arnt that regulates target gene
      transcription by binding to dioxin-responsive sequence motifs. Previously, we
      have demonstrated that the latent form of dioxin receptor present in extracts
      from untreated cells is stably associated with molecular chaperone protein hsp90,
      and Arnt is not a component of this complex. Here, we used a
      coimmunoprecipitation assay to demonstrate that the in vitro-translated dioxin
      receptor, but not Arnt, is stably associated with hsp90. Although it showed
      ligand-binding activity, the in vitro-translated dioxin receptor failed to
      dissociate from hsp90 upon exposure to ligand. Addition of a specific fraction
      from wild-type hepatoma cells, however, to the in vitro-expressed receptor
      promoted dioxin-dependent release of hsp90. This stimulatory effect was mediated
      via the bHLH dimerization and DNA-binding motif of the receptor. Moreover, ligand
      dependent release of hsp90 from the receptor was not promoted by fractionated
      cytosolic extracts from mutant hepatoma cells which are deficient in the function
      of bHLH dioxin receptor partner factor Arnt. Thus, our results provide a novel
      model for regulation of bHLH factor activity and suggest that derepression of the
      dioxin receptor by ligand-induced release of hsp90 may require bHLH-mediated
      concomitant recruitment of an additional cellular factor, possibly the
      structurally related bHLH dimerization partner factor Arnt. In support of this
      model, addition of in vitro-expressed wild-type Arnt, but not a mutated form of
      Arnt lacking the bHLH motif, promoted release of hsp90 from the dioxin receptor
      in the presence of dioxin.

PMID- 8139548
TI  - rac p21 is involved in insulin-induced membrane ruffling and rho p21 is involved
      in hepatocyte growth factor- and 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced membrane ruffling in KB cells.
AB  - Insulin and hepatocyte growth factor (HGF) induced morphologically different
      membrane rufflings in KB cells. Insulin-induced membrane ruffling was inhibited
      by microinjection of rho GDI, an inhibitory GDP/GTP exchange regulator for both
      rho p21 and rac p21 small GTP-binding proteins, but not inhibited by
      microinjection of botulinum exoenzyme C3, known to selectively ADP-ribosylate rho
      p21 and to impair its function. This rho GDI action was prevented by
      comicroinjection with guanosine 5'-(3-O-thio)triphosphate (GTP gamma S)-bound
      rac1 p21. In contrast, HGF-induced membrane ruffling was inhibited by
      microinjection of rho GDI or C3. This rho GDI action was prevented by
      comicroinjection with GTP gamma S-bound rhoA p21, and this C3 action was
      prevented by comicroinjection with GTP gamma S-bound rhoAIle-41 p21, which is
      resistant to C3. Microinjection of either GTP gamma S-bound rac1 p21 or rhoA p21
      alone induced membrane ruffling in the absence of the growth factors. The rac1
      p21-induced membrane ruffling was morphologically similar to the insulin-induced
      kind, whereas rhoA p21-induced ruffling was apparently different from both the
      insulin- and HGF-induced kinds. Membrane ruffling was also induced by 12-O
      tetradecanoylphorbol-13-acetate (TPA), a protein kinase C-activating phorbol
      ester, but not by Ca2+ ionophore or microinjection of a dominant active Ki-ras
      p21 mutant (Ki-rasVal-12 p21). The phorbol ester-induced membrane ruffling was
      morphologically similar to the rhoA p21-induced kind and inhibited by
      microinjection of rho GDI or C3. These results indicate that rac p21 and rho GDI
      are involved in insulin-induced membrane ruffling and that rho p21 and rho GDI
      are involved in HGF- and phorbol ester-induced membrane rufflings.

PMID- 8139550
TI  - Non-Mendelian inheritance of macronuclear mutations is gene specific in
      Paramecium tetraurelia.
AB  - Paramecium tetraurelia contains two types of nuclei, a diploid germinal
      micronucleus and a large transcriptionally active macronucleus. The macronuclear
      genome is formed from the micronuclear DNA during sexual reproduction. Previous
      studies have shown that the processing of the A-type variable surface protein
      gene during formation of a new macronucleus is dependent on the presence of the A
      gene in the old macronucleus. It is not clear if this is a general feature that
      controls the formation of the Paramecium macronuclear genome or a unique feature
      of the A locus. Using micronuclear transplantation, we have constructed a strain
      that has a wild-type micronucleus but has macronuclear deletions of the A- and B
      type surface protein genes. Neither the A nor the B gene is incorporated into the
      new macronucleus after sexual reproduction. Macronuclear transformation of this
      strain with the B gene rescues the B-gene deletion after formation of the next
      macronucleus but has not effect on the A deletion. Similarly, transformation with
      the A gene shows gene-specific rescue for A but not B. The effect of the old
      macronucleus on the processing of the new macronucleus results in a pattern of
      non-Mendelian inheritance of both macronuclear deletions. Progeny from the wild
      type exconjugant are all wild type, and progeny from the A- B- exconjugant are
      mutant. The features of this A- B- non-Mendelian mutant demonstrate that the
      regulation of macronuclear DNA processing is gene specific, and our results open
      the possibility that this type of regulation affects many regions of the
      Paramecium genome.

PMID- 8139549
TI  - Identification of I-plastin, a human fimbrin isoform expressed in intestine and
      kidney.
AB  - The complete cDNA sequence of human intestine-specific plastin (I-plastin) was
      determined from a clone derived by PCR. It consists of a 97-bp 5' untranslated
      region, a 1,887-bp coding region, and a 1,655-bp 3' untranslated region. The
      coding region predicts a 629-residue polypeptide whose sequence displays 86, 75,
      and 73% identities with chicken intestine fimbrin, human T-plastin, and human L
      plastin, respectively. Recombinant I-plastin cross-linked actin filaments into
      bundles in the absence but not in the presence of calcium. The I-plastin gene was
      mapped by PCR to human chromosome 3; the L- and T-plastin genes were previously
      mapped to chromosomes 13 and X, respectively. I-plastin mRNA was detected in the
      small intestine, colon, and kidneys; relatively lower levels of expression were
      detected in the lungs and stomach. In contrast, L-plastin expression was
      restricted to the spleen and other lymph node-containing organs, while T-plastin
      was expressed in a variety of organs, including muscle, brain, uterus, and
      esophagus. In contrast to the situation for the intestine, high levels of L- and
      T-plastin mRNAs were detected in Caco-2, a human colon-derived cell line.
      Immunofluorescence microscopy detected I-plastin in the brush border of the small
      intestine and colon. These results identify I-plastin as the human homolog of
      chicken intestine fimbrin and as a third plastin isoform in humans.

PMID- 8139551
TI  - Structure and function of ribosomal protein S4 genes on the human and mouse sex
      chromosomes.
AB  - The human sex-linked genes RPS4X and RPS4Y encode distinct isoforms of ribosomal
      protein S4. Insufficient expression of S4 may play a role in the development of
      Turner syndrome, the complex human phenotype associated with monosomy X. In mice,
      the S4 protein is encoded by an X-linked gene, Rps4, and is identical to human
      S4X; there is no mouse Y homolog. We report here the organization of the human
      RPS4X and RPS4Y and mouse Rps4 genes. Each gene comprises seven exons; the
      positions of introns are conserved. The 5' flanking sequences of human RPS4X and
      mouse Rps4 are very similar, while RPS4Y diverges shortly upstream of the
      transcription start site. In chickens, S4 is encoded by a single gene that is not
      sex linked. The chicken protein differs from human S4X by four amino acid
      substitutions, all within a region encoded by a single exon. Three of the four
      substitutions are also present in human S4Y, suggesting that the chicken S4 gene
      may have arisen by recombination between S4X- and S4Y-like sequences. Using
      isoform-specific antisera, we determined that human S4X and S4Y are both present
      in translationally active ribosomes. S4Y is about 10 to 15% as abundant as S4X in
      ribosomes from normal male placental tissue and 46,XY cultured cells. In 49,XYYYY
      cells, S4Y is about half as abundant as S4X. In 49,XXXXY cells, S4Y is barely
      detectable. These results bear on the hypothesized role of S4 deficiency in
      Turner syndrome.

PMID- 8139552
TI  - Continued functioning of the secretory pathway is essential for ribosome
      synthesis.
AB  - To explore the regulatory elements that maintain the balanced synthesis of the
      components of the ribosome, we isolated a temperature-sensitive (ts) mutant of
      Saccharomyces cerevisiae in which transcription both of rRNA and of ribosomal
      protein genes is defective at the nonpermissive temperature. Temperature
      sensitivity for growth is recessive and segregates 2:2. A gene that complements
      the ts phenotype was cloned from a genomic DNA library. Sequence analysis
      revealed that this gene is SLY1, encoding a protein essential for protein and
      vesicle transport between the endoplasmic reticulum and the Golgi apparatus. In
      the strain carrying our ts allele of SLY1, accumulation of the carboxypeptidase Y
      precursor was detected at the nonpermissive temperature, indicating that the
      secretory pathway is defective. To ask whether the effect of the ts allele on
      ribosome synthesis was specific for sly1 or was a general result of the
      inactivation of the secretion pathway, we assayed the levels of mRNA for several
      ribosomal proteins in cells carrying ts alleles of sec1, sec7, sec11, sec14,
      sec18, sec53, or sec63, representing all stages of secretion. In each case, the
      mRNA levels were severely depressed, suggesting that this is a common feature in
      mutants of protein secretion. For the mutants tested, transcription of rRNA was
      also substantially reduced. Furthermore, treatment of a sensitive strain with
      brefeldin A at a concentration sufficient to block the secretion pathway also led
      to a decrease of the level of ribosomal protein mRNA, with kinetics suggesting
      that the effect of a secretion defect is manifest within 15 to 30 min. We
      conclude that the continued function of the entire secretion pathway is essential
      for the maintenance of ribosome synthesis. The apparent coupling of membrane
      synthesis and ribosome synthesis suggest the existence of a regulatory network
      that connects the production of the various structural elements of the cell.

PMID- 8139553
TI  - The Aspergillus nidulans abaA gene encodes a transcriptional activator that acts
      as a genetic switch to control development.
AB  - The Aspergillus nidulans abaA gene encodes a protein containing an ATTS DNA
      binding motif and is required for the terminal stages of conidiophore
      development. Results from gel mobility shift and protection, missing-contact, and
      interference footprint assays showed that AbaA binds to the sequence 5'-CATTCY
      3', where Y is a pyrimidine, making both major- and minor-groove contacts.
      Multiple AbaA binding sites are present in the cis-acting regulatory regions of
      several developmentally controlled structural genes as well as those of the
      upstream regulatory gene brlA, the downstream regulatory gene wetA, and abaA
      itself. These cis-acting regulatory regions confer AbaA-dependent transcriptional
      activation in a heterologous Saccharomyces cerevisiae gene expression system.
      From these observations, we propose that the AbaA transcription factor
      establishes a novel set of feedback regulatory loops responsible for
      determination of conidiophore development.

PMID- 8139554
TI  - Transcription inhibits the replication of autonomously replicating plasmids in
      human cells.
AB  - This study addresses the effect of transcription on replication, using a system
      based on autonomously replicating plasmids in human cells. We added
      transcriptional elements from the human cytomegalovirus promoter/enhancer and the
      human beta-actin promoter to autonomously replicating plasmids based on human
      sequences and found that the transcriptional elements inhibited plasmid
      replication. Furthermore, conditional inhibition of plasmid replication was
      demonstrated by using a tetracycline-responsive promoter. We found that
      replication activity of plasmids carrying this promoter was inversely correlated
      with promoter activity. Replication activity was partially restored on plasmids
      when a transcriptional termination sequence was placed directly downstream of the
      promoter element. Transcriptional activity of the promoters and the efficacy of
      the terminator sequence were confirmed by using steady-state RNA analysis. These
      experiments suggest that transcription inhibits DNA replication on these plasmids
      and that the degree of inhibition is dependent on transcription strength. The
      possible significance of these results for chromosomal DNA replication are
      discussed.

PMID- 8139555
TI  - Characterization of cis-acting elements in light regulation of the nuclear gene
      encoding the A subunit of chloroplast isozymes of glyceraldehyde-3-phosphate
      dehydrogenase from Arabidopsis thaliana.
AB  - We have characterized cis-acting elements involved in light regulation of the
      nuclear gene (GapA) encoding the A subunit of chloroplast glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) in Arabidopsis thaliana. Our results show that a
      1.1-kb promoter fragment of the GapA gene is sufficient to confer light
      inducibility and organ specificity in transgenic Nicotiana tabacum (tobacco)
      plants, using the beta-glucuronidase gene of Escherichia coli as the reporter
      gene. Deletion analysis indicates that the -359 to -110 bp region of the GapA
      gene is necessary for light responsiveness. Within this region there are three
      copies of a decamer repeat (termed the Gap box) having the consensus sequence 5'
      CAAATGAA(A/G)A-3', which has not been characterized in the promoter regions of
      other light-regulated genes. A deletion (to -247) producing loss of one copy of
      these elements from the GapA promoter reduces light induction by two- to
      threefold compared with a promoter deletion (to -359) with all three Gap boxes
      present, while deletion of all three Gap boxes (to -110) abolishes light
      induction completely. Gel mobility shift experiments using tobacco nuclei as the
      source of nuclear proteins show that GapA promoter fragments that contain these
      repeats bind strongly to a factor in the nuclear extract and that binding can be
      abolished by synthetic competitors consisting only of a monomer or dimer of the
      Gap box. Furthermore, a trimer, dimer, and monomer of the Gap box show binding
      activity and, like the authentic GapA promoter-derived probes, show binding
      activities that are correlated with Gap box copy number. These results strongly
      suggest that these repeats play important roles in light regulation of the GapA
      gene of A. thaliana.

PMID- 8139556
TI  - MCM1 point mutants deficient in expression of alpha-specific genes: residues
      important for interaction with alpha 1.
AB  - Complexes formed between MCM1 and several coregulatory proteins--alpha 1, alpha
      2, and STE12--serve to govern transcription of the a- and alpha-specific gene
      sets in the yeast Saccharomyces cerevisiae. The N-terminal third of MCM1, MCM1(1
      98), which includes a segment homologous to mammalian serum response factor, is
      capable of performing all of the functions necessary for cell-type-specific gene
      regulation, including DNA binding and interaction with coregulatory proteins. To
      explore the mechanisms by which MCM1(1-98) functions, we isolated point mutants
      that are specifically deficient in alpha-specific gene expression in vivo,
      anticipating that many of the mutants would be impaired for interaction with
      alpha 1. Indeed, in vitro DNA binding assays revealed that a substantial number
      of the mutants were specifically defective in the ability to bind cooperatively
      with alpha 1. Two other mutant classes were also found. One class, exemplified
      most clearly by substitutions at residues 22 and 27, exhibited a general defect
      in DNA binding. The second class, exemplified by substitutions at residues 33 and
      41, was proficient at DNA binding and interaction with alpha 1 in vitro,
      suggesting that these mutants may be defective in achieving an alpha 1-mediated
      conformational change required for transcription activation in vivo. Most of the
      mutants defective for interaction with alpha 1 had substitutions within residues
      69 to 81, which correspond to a region of serum response factor important for
      interaction with its coregulatory proteins. A subset of the mutants with changes
      in this region were also defective in the ability to bind with STE12 to DNA from
      an a-specific gene, suggesting that a common region of MCM1(1-98) mediates
      interaction with both alpha 1 and STE12. This region of MCM1 does not seem to
      constitute an independent domain of the protein, however, because some
      substitutions within this region affected DNA binding. Only two of the MCM1(1-98)
      point mutants showed significant defects in the ability to form complexes with
      alpha 2, suggesting that the mechanism by which MCM1 interacts with alpha 2 is
      distinct from that by which it interacts with alpha 1 and STE12.

PMID- 8139557
TI  - Cellular protein interactions with herpes simplex virus type 1 oriS.
AB  - The herpes simplex virus type 1 (HSV-1) origin of DNA replication, oriS, contains
      an AT-rich region and three highly homologous sequences, sites I, II, and III,
      identified as binding sites for the HSV-1 origin-binding protein (OBP). In the
      present study, interactions between specific oriS DNA sequences and proteins in
      uninfected cell extracts were characterized. The formation of one predominant
      protein-DNA complex, M, was demonstrated in gel shift assays following incubation
      of uninfected cell extracts with site I DNA. The cellular protein(s) that
      comprises complex M has been designated origin factor I (OF-I). The OF-I binding
      site was shown to partially overlap the OBP binding site within site I. Complexes
      with mobilities indistinguishable from that of complex M also formed with site II
      and III DNAs in gel shift assays. oriS-containing plasmid DNA mutated in the OF-I
      binding site exhibited reduced replication efficiency in transient assays,
      demonstrating a role for this site in oriS function. The OF-I binding site is
      highly homologous to binding sites for the cellular CCAAT DNA-binding proteins.
      The binding site for the CCAAT protein CP2 was found to compete for OF-I binding
      to site I DNA. These studies support a model involving the participation of
      cellular proteins in the initiation of HSV-1 DNA synthesis at oriS.

PMID- 8139558
TI  - Bcl-2 blocks p53-dependent apoptosis.
AB  - Adenovirus E1A expression recruits primary rodent cells into proliferation but
      fails to transform them because of the induction of programmed cell death
      (apoptosis). The adenovirus E1B 19,000-molecular-weight protein (19K protein),
      the E1B 55K protein, and the human Bcl-2 protein each cause high-frequency
      transformation when coexpressed with E1A by inhibiting apoptosis. Thus,
      transformation of primary rodent cells by E1A requires deregulation of cell
      growth to be coupled to suppression of apoptosis. The product of the p53 tumor
      suppressor gene induces apoptosis in transformed cells and is required for
      induction of apoptosis by E1A. The ability of Bcl-2 to suppress apoptosis induced
      by E1A suggested that Bcl-2 may function by inhibition of p53. Rodent cells
      transformed with E1A plus the p53(Val-135) temperature-sensitive mutant are
      transformed at the restrictive temperature and undergo rapid and complete
      apoptosis at the permissive temperature when p53 adopts the wild-type
      conformation. Human Bcl-2 expression completely prevented p53-mediated apoptosis
      at the permissive temperature and caused cells to remain in a predominantly
      growth-arrested state. Growth arrest was leaky, occurred at multiple points in
      the cell cycle, and was reversible. Bcl-2 did not affect the ability of p53 to
      localize to the nucleus, nor were the levels of the p53 protein altered. Thus,
      Bcl-2 diverts the activity of p53 from induction of apoptosis to induction of
      growth arrest, and it is thereby identified as a modifier of p53 function. The
      ability of Bcl-2 to bypass induction of apoptosis by p53 may contribute to its
      oncogenic and antiapoptotic activity.

PMID- 8139559
TI  - Direct association of p110 beta phosphatidylinositol 3-kinase with p85 is
      mediated by an N-terminal fragment of p110 beta.
AB  - Phosphatidylinositol (PI) 3-kinase is a heterodimeric enzyme of 85-kDa (p85) and
      110-kDa (p110) subunits implicated in mitogenic signal transduction by virtue of
      its activation in cells transformed by diverse viral oncoproteins and treated
      with various growth factors. We have identified a domain in p110 that mediates
      association with p85 in vitro and in intact cells. A glutathione S-transferase
      fusion protein containing the N-terminal 171 amino-acids of p110 beta bound to
      free p85 in cell lysates. This fusion protein also bound directly to p85
      immobilized on nitrocellulose filters. An epitope-tagged fragment containing
      amino acids 31 to 150 of p110 beta associated with p85 upon expression in intact
      cells. Expression of either an N-terminal fragment of p110 beta or the p85 inter
      SH2 domain, which mediates association with p110, reduced the association of
      endogenous PI 3-kinase activity with the activated platelet-derived growth factor
      receptor in intact cells. Hence, these defined regions of p85 and p110 mediate
      the interaction between the two subunits of PI 3-kinase.

PMID- 8139560
TI  - Developmental and cell type specificity of LINE-1 expression in mouse testis:
      implications for transposition.
AB  - The LINE-1, or L1, family of interspersed repeated DNA constitutes roughly 10% of
      the mammalian genome. Its abundance is due to duplicative transposition via an
      RNA intermediate, L1-encoded proteins, and reverse transcription. Although, in
      principle, transposition may occur in any cell type, expression and transposition
      of a full-length functional element in the germ line are necessary to explain the
      evolutionary genetics of L1. We have found differential expression of L1 protein
      and RNA in germ and somatic cells of the mouse testis during development. Of
      particular interest is the coexpression of full-length, sense-strand L1 RNA and
      L1-encoded protein in leptotene and zygotene spermatocytes at postnatal day 14 of
      development. Expression in meiotic prophase precedes the strand breakage that
      occurs during chromosomal recombination; this offers an avenue for L1 insertion
      into new locations in chromosomal DNA in a cell type that ensures L1 propagation
      in future generations.

PMID- 8139561
TI  - Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA)
      complex, a strong activator of transcription.
AB  - HeLa cells contain a DNA-binding activity which associates with a kappa B-like
      DNA element, termed Rel-related protein-binding element (RRBE), localized
      upstream of the human urokinase promoter. We have purified this activity from the
      HeLa cell cytosol and have shown that it represents a performed heteromeric
      complex between p65 (RelA) and c-Rel. Coexpression of c-Rel and p65 (RelA) by in
      vitro translation formed a DNA-binding complex indistinguishable from purified
      cellular c-Rel-p65 (RelA) in mobility shift assays. The c-Rel-p65 (RelA) complex
      was also formed in COS7 cells upon coexpression of c-Rel and p65 (RelA) cDNAs.
      Cotransfection experiments with COS7 cells, using expression plasmids encoding
      p50, p65 (RelA), or c-Rel and reporter constructs containing a trimerized RRBE,
      revealed that c-Rel-p65 (RelA) is a potent activator of the RRBE, giving rise to
      transcriptional activity higher than that observed with NF-kappa B (p50-p65). In
      the cytosol, the c-Rel-p65 (RelA) complex existed in a latent, non-DNA-binding
      form but could be activated by detergent treatment, suggesting that it was
      associated with an I kappa B protein. Recombinant I kappa B-alpha inhibited the
      DNA-binding activity of c-Rel-p65 (RelA) via association with either c-Rel or p65
      (RelA). Finally, NF-kappa B and c-Rel-p65 (RelA) complexes were found to be
      differentially expressed and regulated in different cells. The two complexes were
      present in equimolar amounts in HeLa cells and K562 cells. Stimulation with
      tetradecanoyl phorbol acetate (TPA) resulted in the nuclear translocation of both
      NF-kappa B and c-Rel-p65 (RelA) in HeLa cells and of NF-kappa B in HepG2 cells
      but had no effect on either complex in K562 cells. In addition, TPA stimulation
      of HepG2 cells induced the expression of a cytosolic latent c-Rel-p65 (RelA)
      complex which, however, was not translocated to the nucleus. In conclusion, our
      findings show that c-Rel-p65 (RelA) is an inducible and very potent
      transcriptional activator which is differentially activated in a cell-type
      specific manner.

PMID- 8139562
TI  - Requirements for intercistronic distance and level of eukaryotic initiation
      factor 2 activity in reinitiation on GCN4 mRNA vary with the downstream cistron.
AB  - Translational control of the GCN4 gene in response to amino acid availability is
      mediated by four short open reading frames in the GCN4 mRNA leader (uORFs) and by
      phosphorylation of eukaryotic initiation factor 2 (eIF-2). We have proposed that
      reducing eIF-2 activity by phosphorylation of its alpha subunit or by a mutation
      in the eIF-2 recycling factor eIF-2B allows ribosomes which have translated the
      5'-proximal uORF1 to bypass uORF2 to uORF4 and reinitiate at GCN4 instead. In
      this report, we present two lines of evidence that all ribosomes which synthesize
      GCN4 have previously translated uORF1, resumed scanning, and reinitiated at the
      GCN4 start site. First, GCN4 expression was abolished when uORF1 was elongated to
      make it overlap the beginning of the GCN4 coding region. Second, GCN4 expression
      was reduced as uORF1 was moved progressively closer to GCN4, decreasing to only
      5% of the level seen in the absence of all uORFs when only 32 nucleotides
      separated uORF1 from GCN4. We additionally found that inserting small synthetic
      uORFs between uORF4 and GCN4 inhibited GCN4 expression under derepressing
      conditions, confirming the idea that reinitiation at GCN4 under conditions of
      diminished eIF-2 activity is proportional to the distance of the reinitiation
      site downstream from uORF1. While uORF4 and GCN4 appear to be equally effective
      at capturing ribosomes scanning downstream from the 5' cap of mRNA, these two
      ORFs differ greatly in their ability to capture reinitiating ribosomes scanning
      from uORF1. When the active form of eIF-2 is present at high levels, reinitiation
      appears to be much more efficient at uORF4 than at GCN4 when each is located very
      close to uORF1. Under conditions of reduced recycling of eIF-2, reinitiation at
      uORF4 is substantially suppressed, which allows ribosomes to reach the GCN4 start
      site; in contrast, reinitiation at GCN4 in constructs lacking uORF4 is unaffected
      by decreasing the level of eIF-2 activity. This last finding raises the
      possibility that time-dependent binding to ribosomes of a second factor besides
      the eIF-2-GTP-Met-tRNA(iMet) ternary complex is rate limiting for reinitiation at
      GCN4. Moreover, our results show that the efficiency of translational
      reinitiation can be strongly influenced by the nature of the downstream cistron
      as well as the intercistronic distance.

PMID- 8139563
TI  - Assembly of mitochondrial ribonucleoprotein complexes involves specific guide RNA
      (gRNA)-binding proteins and gRNA domains but does not require preedited mRNA.
AB  - RNA editing in kinetoplastids probably employs a macromolecular complex, the
      editosome, that is likely to include the guide RNAs (gRNAs) which specify the
      edited sequence. Specific ribonucleoprotein (RNP) complexes which form in vitro
      with gRNAs (H. U. Goringer, D. J. Koslowsky, T. H. Morales, and K. D. Stuart,
      Proc. Natl. Acad. Sci. USA, in press) are potential editosomes or their
      precursors. We find that several factors are important for in vitro formation of
      these RNP complexes and identify specific gRNA-binding proteins present in the
      complexes. Preedited mRNA promotes the in vitro formation of the four major gRNA
      containing RNP complexes under some conditions but is required for the formation
      of only a subcomponent of one complex. The 5' gRNA sequence encompassing the
      RYAYA and anchor regions and the 3' gRNA oligo(U) tail are both important in
      complex formation, since their deletion results in a dramatic decrease of some
      complexes and the absence of others. UV cross-linking experiments identify
      several proteins which are in contact with gRNA and preedited mRNA in
      mitochondrial extracts. Proteins of 25 and 90 kDa are highly specific for gRNAs,
      and the 90-kDa protein binds specifically to gRNA oligo(U) tails. The gRNA
      binding proteins exhibit a differential distribution between the four in vitro
      formed complexes. These experiments reveal several proteins potentially involved
      in RNA editing and indicate that multiple recognition elements in gRNAs are used
      for complex formation.

PMID- 8139564
TI  - Faithful degradation of soybean rbcS mRNA in vitro.
AB  - The mRNA encoding the soybean rbcS gene, SRS4, is degraded into a set of discrete
      lower-molecular-weight products in light-grown soybean seedlings and in
      transgenic petunia leaves. The 5'-proximal products have intact 5' ends, lack
      poly(A) tails, lack various amounts of 3'-end sequences, and are found at higher
      concentrations in the polysomal fraction. To study the mechanisms of SRS4 mRNA
      decay more closely, we developed a cell-free RNA degradation system based on a
      polysomal fraction isolated from soybean seedlings or mature petunia leaves. In
      the soybean in vitro degradation system, endogenous SRS4 mRNA and proximal
      product levels decreased over a 6-h time course. When full-length in vitro
      synthesized SRS4 RNAs were added to either in vitro degradation system, the RNAs
      were degraded into the expected set of proximal products, such as those observed
      for total endogenous RNA samples. When exogenously added SRS4 RNAs already
      truncated at their 3' ends were added to either system, they too were degraded
      into the expected subset of proximal products. A set of distal fragments
      containing intact 3' ends and lacking various portions of 5'-end sequences were
      identified in vivo when the heterogeneous 3' ends of the SRS4 RNAs were removed
      by oligonucleotide-directed RNase H cleavage. Significant amounts of distal
      fragments which comigrated with the in vivo products were also observed when
      exogenous SRS4 RNAs were degraded in either in vitro system. These proximal and
      distal products lacking various portions of their 3' and 5' sequences,
      respectively, were generated in essentially a random order, a result supporting a
      nonprocessive mechanism. Tagging of the in vitro-synthesized RNAs on their 5' and
      3' ends with plasmid vector sequences or truncation of the 3' end had no apparent
      effect on the degradation pattern. Therefore, RNA sequences and/or structures in
      the immediate vicinity of each 3' end point may be important in the degradation
      machinery. Together, these data suggest that SRS4 mRNA is degraded by a
      stochastic mechanism and that endonucleolytic cleavage may be the initial event.
      These plant in vitro systems should be useful in identifying the cis- and trans
      acting factors involved in the degradation of mRNAs.

PMID- 8139565
TI  - Stimulation of polyomavirus DNA replication by wild-type p53 through the DNA
      binding site.
AB  - The tumor suppressor p53 possesses characteristics of a transcription factor; it
      binds to specific DNA sequences and activates transcription from various
      promoters. Here we found that murine wild-type p53 stimulated not only
      transcription but also polyomavirus (Py) DNA replication in a sequence-dependent
      manner. Oncogenic mutant p53, lacking the DNA-binding activity, showed no
      stimulation of Py DNA replication. Deletion of the N-terminal acidic
      transactivation domain of wild-type p53, which completely eliminated the ability
      to stimulate transcription, only impaired the function to stimulate Py DNA
      replication. The replication-stimulating activity of wild-type p53 was impaired
      by the deletion of the C-terminal oligomerization domain as well, without
      affecting the ability to stimulate transcription. The region responsible for the
      sequence-specific DNA-binding activity mapped to the central portion of the p53
      molecule has a minimal activity. The results indicate that both the N-terminal
      and the C-terminal regions significantly contribute to the p53-mediated
      stimulation of Py DNA replication.

PMID- 8139566
TI  - His-154 is involved in the linkage of the Saccharomyces cerevisiae L-A double
      stranded RNA virus Gag protein to the cap structure of mRNAs and is essential for
      M1 satellite virus expression.
AB  - The coat protein (Gag) of the double-stranded RNA virus L-A was previously shown
      to form a covalent bond with the cap structure of eukaryotic mRNAs. Here, we
      identify the linkage as a phosphoroimidazole bond between the alpha phosphate of
      the cap structure and a nitrogen in the Gag protein His-154 imidazole side chain.
      Mutations of His-154 abrogate the ability of Gag to bind to the cap structure,
      without affecting cap recognition, in vivo virus particle formation from an L-A
      cDNA clone, or in vitro specific binding and replication of plus-stranded single
      stranded RNA. However, genetic analyses demonstrate that His-154 is essential for
      M1 satellite virus expression.

PMID- 8139567
TI  - The interaction of small domains between the subunits of phosphatidylinositol 3
      kinase determines enzyme activity.
AB  - Previous studies have suggested that the two subunits of phosphatidylinositol
      (PI) 3-kinase, p85 and p110, function as localizing and catalytic subunits,
      respectively. Using recombinant p85 and p110 molecules, we have reconstituted the
      specific interaction between the two subunits of mouse PI 3-kinase in cells and
      in vitro. We have previously shown that the region between the two Src homology 2
      (SH2) domains of p85 is able to form a functional complex with the 110-kDa
      subunit in vivo. In this report, we identify the corresponding domain in p110
      which directs the binding to p85. We demonstrate that the interactive domains in
      p85 and p110 are less than 103 and 124 amino acids, respectively, in size. We
      also show that the association of p85 and p110 mediated by these domains is
      critical for PI 3-kinase activity. Surprisingly, a complex between a 102-amino
      acid segment of p85 and the full-length p110 molecule is catalytically active,
      whereas p110 alone has no activity. In addition to the catalytic domain in the
      carboxy-terminal region, 123 amino acids at the amino terminus of p110 were
      required for catalytic activity and were sufficient for the interaction with p85.
      These results indicate that the 85-kDa subunit, previously thought to have only a
      linking role in localizing the p110 catalytic subunit, is an important component
      of the catalytic complex.

PMID- 8139568
TI  - Induction versus progression of brain tumor development: differential functions
      for the pRB- and p53-targeting domains of simian virus 40 T antigen.
AB  - The ability of simian virus 40-encoded large T antigen to disrupt the growth
      control of a variety of cell types is related to its ability to interfere with
      certain cellular proteins, such as p53 and the retinoblastoma susceptibility gene
      product (pRB). We have used wild-type and mutant forms of T antigen in transgenic
      mice to dissect the roles of pRB, p53, and other cellular proteins in
      tumorigenesis of different cell types. In this study, using a cell-specific
      promoter to target expression specifically to brain epithelium (the choroid
      plexus) and to B and T lymphoid cells, we characterize the tumorigenic capacity
      of a T-antigen fragment that comprises only the amino-terminal 121 residues. This
      fragment (dl1137) retains the ability to interact with pRB and p107 but lacks the
      p53-binding domain. While loss of the p53-binding region results in loss of the
      capacity to induce lymphoid abnormalities, dl1137 retains the ability to induce
      choroid plexus tumors that are histologically indistinguishable from those
      induced by wild-type T antigen. Tumors induced by dl1137 develop much more
      slowly, however, reaching an end point at around 8 months of age rather than at 1
      to 2 months. Analysis of tumor progression indicates that tumor induction by
      dl1137 does not require secondary genetic or epigenetic events. Rather, the tumor
      growth rate is significantly slowed, indicating that the T-antigen C-terminal
      region contributes to tumor progression in this cell type. In contrast, the pRB
      binding region appears essential for tumorigenesis as mutation of residue 107,
      known to disrupt pRB and p107 binding to wild-type T antigen, abolishes the
      ability of the dl1137 protein to induce growth abnormalities in the brain.

PMID- 8139569
TI  - Complementation of mutant and wild-type human mitochondrial DNAs coexisting since
      the mutation event and lack of complementation of DNAs introduced separately into
      a cell within distinct organelles.
AB  - The rules that govern complementation of mutant and wild-type mitochondrial
      genomes in human cells were investigated under different experimental conditions.
      Among mitochondrial transformants derived from an individual affected by the
      MERRF (myoclonus epilepsy associated with ragged red fibers) encephalomyopathy
      and carrying in heteroplasmic form the mitochondrial tRNA(Lys) mutation
      associated with that syndrome, normal protein synthesis and respiration was
      observed when the wild-type mitochondrial DNA exceeded 10% of the total
      complement. In these transformants, the protective effect of wild-type
      mitochondrial DNA was shown to involve interactions of the mutant and wild-type
      gene products. Very different results were obtained in experiments in which two
      mitochondrial DNAs carrying nonallelic disease-causing mutations were
      sequentially introduced within distinct organelles into the same human
      mitochondrial DNA-less (rho 0) cell. In transformants exhibiting different ratios
      of the two genomes, no evidence of cooperation between their products was
      observed, even 3 months after the introduction of the second mutation. These
      results pointed to the phenotypic independence of the two genomes. A similar
      conclusion was reached in experiments in which mitochondria carrying a
      chloramphenicol resistance-inducing mitochondrial DNA mutation were introduced
      into chloramphenicol-sensitive cells. A plausible interpretation of the different
      results obtained in the latter two sets of experiments, compared with the
      complementation behavior observed in the heteroplasmic MERRF transformants, is
      that in the latter, the mutant and wild-type genomes coexisted in the same
      organelles from the time of the mutation. This would imply that the way in which
      mitochondrial DNA is sorted among different organelles plays a fundamental role
      in determining the oxidative-phosphorylation phenotype in mammalian cells. These
      results have significant implications for mitochondrial genetics and for studies
      on the transmission and therapy of mitochondrial DNA-linked diseases.

PMID- 8139570
TI  - Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase.
AB  - The accumulation of assembled holoenzymes composed of regulatory D-type cyclins
      and their catalytic partner, cyclin-dependent kinase 4 (cdk4), is rate limiting
      for progression through the G1 phase of the cell cycle in mammalian fibroblasts.
      Both the synthesis and assembly of D-type cyclins and cdk4 depend upon serum
      stimulation, but even when both subunits are ectopically overproduced, they do
      not assemble into complexes in serum-deprived cells. When coexpressed from
      baculoviral vectors in intact Sf9 insect cells, cdk4 assembles with D-type
      cyclins to form active protein kinases. In contrast, recombinant D-type cyclin
      and cdk4 subunits produced in insect cells or in bacteria do not assemble as
      efficiently into functional holoenzymes when combined in vitro but can be
      activated in the presence of lysates obtained from proliferating mammalian cells.
      Assembly of cyclin D-cdk4 complexes in coinfected Sf9 cells facilitates
      phosphorylation of cdk4 on threonine 172 by a cdk-activating kinase (CAK).
      Assembly can proceed in the absence of this modification, but cdk4 mutants which
      cannot be phosphorylated by CAK remain catalytically inactive. Therefore,
      formation of the cyclin D-cdk4 complex and phosphorylation of the bound catalytic
      subunit are independently regulated, and in addition to the requirement for CAK
      activity, serum stimulation is required to promote assembly of the complexes in
      mammalian cells.

PMID- 8139571
TI  - In vitro mutagenesis of Caenorhabditis elegans cuticle collagens identifies a
      potential subtilisin-like protease cleavage site and demonstrates that carboxyl
      domain disulfide bonding is required for normal function but not assembly.
AB  - The importance of conserved amino acids in the amino and carboxyl non-Gly-X-Y
      domains of Caenorhabditis elegans cuticle collagens was examined by analyzing
      site-directed mutations of the sqt-1 and rol-6 collagen genes in transgenic
      animals. Altered collagen genes on transgenic arrays were shown to produce
      appropriate phenotypes by injecting in vivo cloned mutant alleles. Equivalent
      alterations in sqt-1 and rol-6 generally produced the same phenotypes, indicating
      that conserved amino acids in these two collagens have similar functions. Serine
      substitutions for either of two conserved carboxyl domain cysteines produced LRol
      phenotypes. Substitution for both cysteines in sqt-1 also resulted in an LRol
      phenotype, demonstrating that disulfide bonding is important for normal function
      but not required for assembly. Arg-1 or Arg-4 to Cys mutations in homology block
      A (HBA; consensus, 1-RXRRQ-5; in the amino non-Gly-X-Y domain) caused RRol
      phenotypes, while the same alteration at Arg-3 had no effect, indicating that Arg
      3 is functionally different from Arg-1 and Arg-4. Substitutions of Arg-4 with
      Ser, Leu, or Glu also produced the RRol phenotype, while Lys substitutions for
      Arg-1 or Arg-4 did not generate any abnormal phenotypes. His substitutions for
      Arg-1 or Arg-4 caused somewhat less severe RRol phenotypes. Therefore, strong
      positively charged residues, Arg or Lys, are required at positions 1 and 4 for
      normal function. The conserved pattern of arginines in HBA matches the cleavage
      sites of the subtilisin-like endoproteinases. HBA may be a cleavage site for a
      subtilisin-like protease, and cleavage may be important for cuticle collagen
      processing.

PMID- 8139572
TI  - Modulating the potency of an activator in a yeast in vitro transcription system.
AB  - The intrinsic stimulatory potential or potency of a eukaryotic gene activator is
      controlled by the interaction between the activation domain and the
      transcriptional machinery. To further understand this interaction, we undertook a
      biochemical study to identify parameters that could be used to modulate activator
      potency. We considered how varying the number of activation domains, their
      flexibility, and the number of promoter sites affects potency in a yeast nuclear
      extract. The effects of GAL4 derivatives bearing either one, two, or four herpes
      simplex virus VP16 activation domains (amino acids 413 to 454) were measured on
      DNA templates containing one or two GAL4 sites in a Saccharomyces cerevisiae
      nuclear extract. We found that multimerized VP16 activation domains acted
      synergistically to increase the potency of the activators. The spacing between
      the activation domains was critical, such that the increased flexibility imparted
      by a protein linker contributed to increased activator potency. With highly
      potent activators, the levels of transcription stimulated on a single site were
      saturating, whereas the stimulatory effect of weaker activators increased with
      the number of sites. We discuss how these biochemical studies relate to the
      mechanism of gene activation and synergy in a yeast in vitro system.

PMID- 8139573
TI  - Identification and characterization of a novel yeast gene: the YGP1 gene product
      is a highly glycosylated secreted protein that is synthesized in response to
      nutrient limitation.
AB  - Nutrient starvation in the yeast Saccharomyces cerevisiae leads to a number of
      physiological changes that accompany entry into stationary phase. The expression
      of genes whose products play a role in stress adaptation is regulated in a manner
      that allows the cell to sense and respond to changing environmental conditions.
      We have identified a novel yeast gene, YGP1, that displays homology to the
      sporulation-specific SPS100 gene. The expression of YGP1 is regulated by nutrient
      availability. The gene is expressed at a basal level during "respiro
      fermentative" (logarithmic) growth. When the glucose concentration in the medium
      falls below 1%, the YGP1 gene is derepressed and the gene product, gp37, is
      synthesized at levels up to 50-fold above the basal level. The glucose-sensing
      mechanism is independent of the SNF1 pathway and does not operate when cells are
      directly shifted to a low glucose concentration. The expression of YGP1 also
      responds to the depletion of nitrogen and phosphate, indicating a general
      response to nutrient deprivation. These results suggest that the YGP1 gene
      product may be involved in cellular adaptations prior to stationary phase and may
      be a useful marker protein for monitoring early events associated with the stress
      response.

PMID- 8139575
TI  - A unique subpopulation of murine DNA polymerase alpha/primase specifically
      interacts with polyomavirus T antigen and stimulates DNA replication.
AB  - Murine cells or cell extracts support the replication of plasmids containing the
      replication origin (ori-DNA) of polyomavirus (Py) but not that of simian virus 40
      (SV40), whereas human cells or cell extracts support the replication of SV40 ori
      DNA but not that of Py ori-DNA. It was shown previously that fractions containing
      DNA polymerase alpha/primase from permissive cells allow viral ori-DNA
      replication to proceed in extracts of nonpermissive cells. To extend these
      observations, the binding of Py T antigen to both the permissive and
      nonpermissive DNA polymerase alpha/primase was examined. Py T antigen was
      retained by a murine DNA polymerase alpha/primase but not by a human DNA
      polymerase alpha/primase affinity column. Likewise, a Py T antigen affinity
      column retained DNA polymerase alpha/primase activity from murine cells but not
      from human cells. The murine fraction which bound to the Py T antigen column was
      able to stimulate Py ori-DNA replication in the nonpermissive extract. However,
      the DNA polymerase alpha/primase activity in this murine fraction constituted
      only a relatively small proportion (approximately 20 to 40%) of the total murine
      DNA polymerase alpha/primase that had been applied to the column. The DNA
      polymerase alpha/primase purified from the nonbound murine fraction, although far
      more replete in this activity, was incapable of supporting Py DNA replication.
      The two forms of murine DNA polymerase alpha/primase also differed in their
      interactions with Py T antigen. Our data thus demonstrate that there are two
      distinct populations of DNA polymerase alpha/primase in murine cells and that
      species-specific interactions between T antigen and DNA polymerases can be
      identified. They may also provide the basis for initiating a novel means of
      characterizing unique subpopulations of DNA polymerase alpha/primase.

PMID- 8139574
TI  - The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is
      influenced by amino-acid residues adjacent to the recognition helix.
AB  - Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (HNF-3 alpha, -3
      beta, and -3 gamma) are known to regulate the transcription of liver-specific
      genes. The HNF-3 proteins bind to DNA as a monomer through a modified helix-turn
      helix, known as the winged helix motif, which is also utilized by a number of
      developmental regulators, including the Drosophila homeotic forkhead (fkh)
      protein. We have previously described the isolation, from rodent tissue, of an
      extensive family of tissue-specific HNF-3/fkh homolog (HFH) genes sharing
      homology in their winged helix motifs. In this report, we have determined the
      preferred DNA-binding consensus sequence for the HNF-3 beta protein as well as
      for two divergent family members, HFH-1 and HFH-2. We show that these HNF-3/fkh
      proteins bind to distinct DNA sites and that the specificity of protein
      recognition is dependent on subtle nucleotide alterations in the site. The HNF-3,
      HFH-1, and HFH-2 consensus binding sequences were also used to search DNA
      regulatory regions to identify potential target genes. Furthermore, an analysis
      of the DNA-binding properties of a series of HFH-1/HNF-3 beta protein chimeras
      has allowed us to identify a 20-amino-acid region, located adjacent to the DNA
      recognition helix, which contributes to DNA-binding specificity. These sequences
      are not involved in base-specific contacts and include residues which diverge
      within the HNF-3/fkh family. Replacement of this 20-amino-acid region in HNF-3
      beta with corresponding residues from HFH-1 enabled the HNF-3 beta recognition
      helix to bind only HFH-1-specific DNA-binding sites. We propose a model in which
      this 20-amino-acid flanking region influences the DNA-binding properties of the
      recognition helix.

PMID- 8139576
TI  - FTZ-F1-related orphan receptors in Xenopus laevis: transcriptional regulators
      differentially expressed during early embryogenesis.
AB  - Orphan receptors of the FTZ-F1-related group of nuclear receptors (xFF1r) were
      identified in Xenopus laevis by isolation of cDNAs from a neurula stage library.
      Two cDNAs were found, which encode full length, highly related receptor proteins,
      xFF1rA and B, whose closet relative known so far is the murine LRH-1 orphan
      receptor. xFF1rA protein expressed by a recombinant vaccinia virus system
      specifically binds to FTZ-F1 response elements (FRE; PyCAAGGPyCPu). In
      cotransfection studies, xFF1rA constitutively activates transcription, in a
      manner dependent on the number of FREs. The amounts of at least four mRNAs
      encoding full-length receptors greatly increase between gastrula and early
      tailbud stages and decrease at later stages. At early tailbud stages, xFTZ-F1
      related antigens are found in all nuclei of the embryo.

PMID- 8139577
TI  - Identical components of yeast transcription factor IIIB are required and
      sufficient for transcription of TATA box-containing and TATA-less genes.
AB  - Specific transcription by RNA polymerase III requires recognition of the promoter
      bound transcription factor IIIB (TFIIIB), of which the TATA-binding protein (TBP)
      is a subunit. The recruitment of TFIIIB to TATA-less genes is mediated by protein
      protein interactions with transcription factor IIIC (TFIIIC) bound to the box A
      and box B elements. Here we examine interactions involved in the recruitment of
      TFIIIB to the TATA element-containing yeast U6 small nuclear RNA gene SNR6.
      TFIIIC is not required for the formation of TFIIIB-SNR6 gene complexes with
      purified components. The same three components of TFIIIB that are necessary for
      TFIIIC-dependent transcription of tRNA genes (recombinant TBP and Brf and the
      denaturing-gel-purified 90-kDa subunit) are required and sufficient for TATA box
      directed U6 transcription. Despite its TFIIIC-independent, DNA sequence-dependent
      assembly, the TFIIIB-SNR6 complex shares important features with tDNA- and 5S
      rDNA-TFIIIB complexes, such as extent and location of footprint, stability, and
      resistance to heparin. These properties are clearly distinct from those of a TBP
      SNR6 complex. In the SNR6 gene, box B, the primary binding site for TFIIIC, is
      suboptimally spaced relative to box A. At limiting TBP concentrations and on bare
      DNA, TFIIIC stimulates the formation of TFIIIB complexes with SNR6 but
      contributes poorly, at best, to the formation of properly placed complexes.

PMID- 8139578
TI  - Cholesterol and bile acids regulate cholesterol 7 alpha-hydroxylase expression at
      the transcriptional level in culture and in transgenic mice.
AB  - Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is the rate-limiting enzyme
      in bile acid biosynthesis. It is subject to a feedback control, whereby high
      levels of bile acids suppress its activity, and cholesterol exerts a positive
      control. It has been suggested that posttranscriptional control plays a major
      part in that regulation. We have studied the mechanisms by which cholesterol and
      bile acids regulate expression of the 7 alpha-hydroxylase gene and found it to be
      solely at the transcriptional level by using two different approaches. First,
      using a tissue culture system, we localized a liver-specific enhancer located 7
      kb upstream of the transcriptional initiation site. We also showed that low
      density lipoprotein mediates transcriptional activation of chimeric genes,
      containing either the 7 alpha-hydroxylase or the albumin enhancer in front of the
      7 alpha-hydroxylase proximal promoter, to the same extent as the in vivo
      cholesterol-mediated regulation of 7 alpha-hydroxylase mRNA. In a second
      approach, using transgenic mice, we have found that expression of an albumin
      enhancer-7 alpha-hydroxylase-lacZ fusion gene is restricted to the liver and is
      regulated by cholesterol and bile acids in a manner quantitatively similar to
      that of the endogenous gene. We also found, that a liver-specific enhancer is
      necessary for expression of the rat 7 alpha-hydroxylase gene, in agreement with
      the tissue culture experiments. Together, these results demonstrate that
      cholesterol and bile acids regulate the expression of the 7 alpha-hydroxylase
      gene solely at the transcriptional level.

PMID- 8139580
TI  - More efficient peptide binding to MHC class II molecules during cathepsin B
      digestion of Ii than after Ii release.
AB  - The binding of a T cell-presented peptide to MHC class II alpha,beta chains
      occurs as a concurrent process with the release of the associated invariant chain
      (Ii) by cathepsin B. Ii was digested by cathepsin B from solubilized, MHC class
      II alpha,beta,Ii complexes in the presence of N-hydroxysuccinimidyl-4
      azidobenzoate-conjugated, 125I-labeled, influenza virus matrix (18-29) peptide.
      The peptide was crosslinked where it became bound. This HLA-DR1-restricted
      peptide bound about three times more efficiently to class II alpha,beta chains of
      DR1-positive B cells when present during cathepsin B digestion of Ii than when
      added afterward, also at pH 5.0. Binding was competed by similarly DR-restricted
      peptides. Cathepsin D cleaved Ii but did not enhance peptide binding. However, a
      trace level of cathepsin D, added to the assay for peptide binding in the
      presence of cathepsin B, further enhanced peptide binding about three times.
      These experiments support an hypothesis for the staged release of Ii fragments by
      cathepsin D and cathepsin B, catalyzing at one point the insertion of a peptide
      into the antigen binding site formed by class II alpha and beta chains.

PMID- 8139581
TI  - A bifunctional murine::human chimeric antibody with one antigen-binding arm
      replaced by bacterial beta-lactamase.
AB  - We here report the genetic engineering of a murine::human chimeric antibody-
      directed against the tumor marker human placental alkaline phosphatase--in which
      one antigen-binding arm (Fab) has been replaced by Escherichia coli beta
      lactamase (Bla). A mutated Bla gene in which the termination codon had been
      replaced by GAG, was fused in-phase to the cDNA sequence encoding the hinge
      region, CH2 and CH3 of the human IgG3 heavy chain. The resulting BlaHG3f fusion
      gene was placed under control of the Simian Virus 40 late promoter, and
      transiently expressed in COS-1 cells together with the genes encoding the murine
      light and murine::human chimeric heavy chains. Approximately 200 ng/ml of
      correctly assembled bifunctional antibody-Bla immunoconjugates were detected in
      the culture supernatant. This observation indicates that Bla (with its own leader
      peptide) can efficiently direct secretion into the culture medium of adventitious
      sequences fused at its C-terminus. Furthermore, the assembly in the Fc region was
      not affected by steric hindrance due to a Bla moiety and an Fab arm in close
      proximity. The antibody-Bla immunoconjugate could be of therapeutic value for the
      activation of cephalosporin-based anti-cancer prodrugs at the tumor site.
      Moreover, the expression strategy adopted here is particularly suitable for a
      quick and convenient analysis of newly designed gene products in which the Bla
      moiety has been replaced by other enzymes or by antigen-binding fragments in
      order to engineer bispecific antibodies.

PMID- 8139582
TI  - Restricted VH gene usage by murine hybridomas directed against the human N, but
      not M, blood group antigen.
AB  - The M and N human blood group antigens are complex glycopeptide determinants at
      the amino terminus of the red blood cell membrane glycoprotein, glycophorin A.
      The heavy and light chain variable region cDNA sequences were determined for
      seven murine monoclonal antibodies recognizing glycophorin A. Three of the
      antibodies were anti-M and four were anti-N. Each of the anti-M antibodies was
      composed of VH and VL regions derived from distinct germline gene families (VH1
      (J558), VH4 (X24), VH5 (7183), VK5, VK8, and VK19). In contrast, all four anti-N
      heavy chains were composed of VH regions derived from the VH2 (Q52) germline gene
      family and all used the same J4 gene segment. In addition, two of the anti-N
      light chains were composed of VK regions from the VK8 germline gene family and
      used the J1 gene segment. Since each anti-N hybridoma was derived from different
      mice immunized by different protocols, these results suggest that the murine
      immune response to the N, but not the M, human blood group antigen is restricted.

PMID- 8139579
TI  - Histone H1 expressed in Saccharomyces cerevisiae binds to chromatin and affects
      survival, growth, transcription, and plasmid stability but does not change
      nucleosomal spacing.
AB  - Histone H1 is proposed to serve a structural role in nucleosomes and chromatin
      fibers, to affect the spacing of nucleosomes, and to act as a general repressor
      of transcription. To test these hypotheses, a gene coding for a sea urchin
      histone H1 was expressed from the inducible GAL1 promoter in Saccharomyces
      cerevisiae by use of a YEp vector for high expression levels (strain YCL7) and a
      centromere vector for low expression levels (strain YCL1). The H1 protein was
      identified by its inducibility in galactose, its apparent molecular weight, and
      its solubility in 5% perchloric acid. When YCL7 was shifted from glucose to
      galactose for more than 40 h to achieve maximal levels of H1, H1 could be
      copurified in approximately stoichiometric amounts with core histones of Nonidet
      P-40-washed nuclei and with soluble chromatin fractionated on sucrose gradients.
      While S. cerevisiae tolerated the expression of low levels of H1 in YCL1 without
      an obvious phenotype, the expression of high levels of H1 correlated with greatly
      reduced survival, inhibition of growth, and increased plasmid loss but no obvious
      change in the nucleosomal repeat length. After an initial induction, RNA levels
      for GAL1 and H1 were drastically reduced, suggesting that H1 acts by the
      repression of galactose-induced genes. Similar effects, but to a lower extent,
      were observed when the C-terminal tail of H1 was expressed.

PMID- 8139583
TI  - Homologous restriction factor: effect on complement C8 and C9 uptake and lysis.
AB  - Homologous restriction factor (HRF) is a complementary regulatory protein found
      on the surface of human erythrocytes and other cell types. It has the function of
      blocking the lytic action of the membrane attack complex (MAC) of complement when
      incorporated into a membrane. HRF was found to inhibit not only the MAC composed
      of the proteins C5b-9, but also the C5b-8 complex. When 125I-labelled HRF was
      allowed to insert into an erythrocyte target, lysis by C5b-8 was reduced by about
      80%. When human erythrocytes were treated with antibody to HRF, which bound to
      and presumably blocked the action of HRF, lysis by C5b-8 increased. This increase
      was not caused by additional binding of C8 on the cell membrane. When HRF was
      inserted into a target cell membrane, it had the effect of reducing the amount of
      C9 that could bind to very low levels, in one experiment from 6000 molecules per
      cell to about 500 molecules per cell. When this value was compared to the number
      of C7 molecules that bound, it was found that HRF reduced the amount of C9 bound
      to the level of C7 that was bound. HRF seemed to reduce the number of molecules
      of C9 that could bind to the C5b-8 complex so that only one C9 bound per complex.

PMID- 8139584
TI  - Characterization of physiologic breakdown products of the complement fragment Ba.
AB  - To better characterize the activation products of factor B which are generated
      under physiologic conditions Ba was purified directly from human EDTA-plasma by
      immunoaffinity chromatography using anti-Ba Sepharose. SDS-PAGE analysis revealed
      the existence of degradation products of the Ba fragment which were truncated at
      the carboxyterminus. A monoclonal antibody (mAb D22/3) was produced by immunizing
      mice with a synthetic peptide which corresponds to the Ba carboxyterminus (Glu215
      Arg234). This mAb was found to react with an epitope (Ba neo-epitope), which is
      newly formed after the generation of Ba from its precursor protein factor B. This
      neoantigenic determinant is absent both in factor B and the desArg/Lys Ba
      derivatives. The conversion of Ba by carboxypeptidases in human serum was
      monitored using an assay which is based on mAb D22/3, revealing a half-life of Ba
      in serum of 150 min. Furthermore, this assay allowed to quantitate plasma levels
      of intact and degraded Ba in healthy probands and in patients with chronic renal
      failure. The processing of the Ba carboxyterminus may be of functional relevance
      as the biological activity of the Ba fragment which had been shown to suppress
      human B lymphocyte functions in vitro resides in its carboxyterminal amino acid
      sequence.

PMID- 8139585
TI  - Identification of a T cell-specific transcriptional enhancer 3' of the human T
      cell receptor gamma locus.
AB  - Positive and negative transcriptional regulatory mechanisms are thought to play a
      major role in the expression of T cell antigen receptor (TCR) genes. Since the
      alpha beta and gamma delta T cell receptor heterodimers are expressed in a
      mutually exclusive fashion and since TCR genes are sequentially activated during
      T cell ontogeny, transcriptional activation and repression must at least in part
      determine T lineage-specific and developmental-specific expression of these
      genes. We have identified a transcriptional enhancer located 6.5 kb downstream
      from the human T cell receptor gamma (TRG) locus. The nucleotide sequence of the
      enhancer core element shows strong sequence homology to the recently identified
      murine C gamma 1 enhancer. The enhancer demonstrates T cell-specific activity,
      but not gamma delta sublineage-specificity in combination with either a
      heterologous or gene-specific promoter. Thus, additional regulatory elements may
      be required to repress the expression of rearranged TRG genes in non-gamma delta
      T cells.

PMID- 8139586
TI  - Synergistic monoclonal antibodies' interactions and their use for determination
      of antibody specificities.
AB  - Three monoclonal antibodies (MAb 3C11, F11 and 10D6) to human growth hormone
      (hGH) recognize independent epitopes and show mutually enhancing properties.
      Thus, 125I-hGH binding to each of these MAb augmented significantly in the
      presence of each one of the other two MAb. Moreover, preincubation of the hormone
      with paired MAb gave rise to ternary complexes (Ag:Ab1:Ab2) which bound better
      than the free tracer to the third MAb previously captured on a solid-phase.
      Highly stable quaternary complexes (Ag:Ab1:Ab2:Ab3) were thus formed. Since Fab
      fragments from the three MAb displayed the same behavior as the whole Ab
      molecule, neither the formation of multimolecular cyclic complexes nor the
      occurrence of interactions through Fc fragments could explain the reciprocal MAb
      binding enhancement. Therefore, the results obtained suggest that MAb 3C11, F11
      and 10D6 produce some modification in the Ag, each one improving the binding of
      the two other MAb. Additionally, the inhibition of the formation of quaternary
      complexes between the MAb and hGH was used to evaluate specific Ab populations in
      polyclonal antisera, avoiding the masking effect of enhancing Ab. The results
      obtained indicate that Ab directed to the hGH antigenic domains defined by MAb
      3C11, F11 and 10D6 could be detected in spite of the presence of enhancing Ab to
      all three MAb.

PMID- 8139587
TI  - Late presentation of congenital muscular torticollis: use of MR imaging and CT
      scan in diagnosis.
AB  - A 17-year old boy presented with a 10-year history of progressive head tilt to
      the right. Bilateral posterolateral cervical pain was mild and he was fully
      functional. The right sternocleidomastoid (SCM) muscle was prominent without
      rotation of the head to the left. The SCM had a cord-like consistency on
      palpation. Magnetic resonance (MR) and computed tomography (CT) scan imaging of
      the neck musculature suggested fibrous tissue within the substance of the muscle.
      This was histopathologically confirmed when the right SCM was surgically explored
      and resected. Congenital muscular torticollis is usually seen in newborns,
      infants, and children but may also present in adolescence and young adulthood. It
      should be included in the differential diagnosis of cervical dystonia as one of
      the nondystonic causes of abnormal head posture. Combined use of MR and CT scan
      of neck muscles may be of help in the diagnosis.

PMID- 8139588
TI  - Masticatory muscle spasm in a non-Japanese patient with Satoyoshi syndrome
      successfully treated with botulinum toxin.
AB  - A non-Japanese patient with Satoyoshi syndrome is presented. Severe masticatory
      muscle spasms interfered with feeding, but were successfully treated with
      botulinum toxin.

PMID- 8139589
TI  - Temporary symptom worsening caused by manidipine hydrochloride in two patients
      with Parkinson's disease.

PMID- 8139590
TI  - Parkinsonism due to a subdural hematoma.

PMID- 8139591
TI  - Biballism caused by bilateral infarction in the substantia nigra.

PMID- 8139592
TI  - Bilateral akinesia in drug-induced parkinsonism after a subthalamic lesion.

PMID- 8139593
TI  - Steroid-responsive chorea in childhood following cardiac transplantation.

PMID- 8139594
TI  - The Clinton effect and hemiballism.

PMID- 8139595
TI  - Meperidine and reversible parkinsonism.

PMID- 8139596
TI  - Atypical blepharospasm responsive to sodium valproate.

PMID- 8139597
TI  - Glutathion S-transferase (class mu) phenotype in Parkinson's disease.

PMID- 8139598
TI  - Cerebral toxoplasmosis and movement disorders.

PMID- 8139600
TI  - Posttraumatic tic disorder.

PMID- 8139599
TI  - Platelet mitochondrial DNA in Parkinson's disease.

PMID- 8139601
TI  - Levodopa-induced dyskinesias in Parkinson's disease phenomenology and
      pathophysiology.
AB  - The aim of this study was to provide further insight into the phenomenology and
      pathophysiology of monophasic and biphasic dyskinesias induced by levodopa in
      Parkinson's disease. For this purpose, the type, localization, severity, and
      timing of dyskinesias were evaluated in 15 parkinsonian patients in relation to
      motor disability after administration of levodopa using a video-electromyographic
      recording device. Foot-dystonia, myoclonus, and akathisia were observed in most
      patients. The dyskinesias started in the foot, usually on the side most affected
      by the disease, and spread in an "ascending wave" to the contralateral side, the
      trunk, and upper extremities. In a few patients, onset was axial, spreading
      almost instantaneously to all limbs. The dyskinesias were dystonic and ballistic
      at the start, and became increasingly choreic as they attained the upper limbs.
      Their intensity was maximal in the lower limbs, then progressively decreased,
      while increasing in upper limbs and head. The results indicate that there is no
      strict dichotomy between biphasic and monophasic dyskinesias. In other words,
      there is a "continuum" between the first dyskinesias and those observed during
      the period of maximal clinical improvement. These dyskinesias can also appear in
      reverse order, as if there were an "oscillator" determining a sequence of
      alternating patterns.

PMID- 8139602
TI  - Dystonia and dyskinesia in glutaric aciduria type I: clinical heterogeneity and
      therapeutic considerations.
AB  - Glutaric aciduria type I (GA-I) is an inborn error in the degradation of lysine,
      hydroxylysine, and tryptophan due to a deficiency of glutaryl-CoA dehydrogenase.
      Glutaric, 3-OH-glutaric, and glutaconic acids are excreted in the urine,
      particularly during intercurrent illness. The enzyme may be assayed in
      leukocytes, cultured fibroblasts and chorionic villi. Twelve new cases, 9 months
      16 years of age, are reported, comprising all known cases of GA-I in Sweden and
      Norway. Ten had a severe dystonic-dyskinetic disorder, one had a mild
      hyperkinetic disorder, and one was asymptomatic. Two children died in a state of
      hyperthermia. Carnitine deficiency and malnutrition developed in patients with
      severe dystonia and dysphagia, which necessitated substitution and gastrostomy. A
      slowly progressive dyskinetic disorder developed in spite of adequate early
      dietary treatment in one subject. Macrocephaly was found in three. Computed
      tomography and magnetic resonance investigations in 10 showed deep bitemporal
      spaces in 7. Neuropsychological testing of 8 of 12 subjects demonstrated
      receptive language function to be superior to expressive language and motor
      function. Cognitive functions were obviously less affected than motor functions.
      A review of 57 pooled cases showed that a severe dystonic syndrome developed in
      77%, a mild extrapyramidal syndrome in 10%, and 12% were asymptomatic. This
      disorder may pass undetected in the cerebral palsy and mentally retarded child
      and adult populations. Repeated urine examinations of organic acids in the urine
      and enzyme assay may be necessary to confirm GA-I.

PMID- 8139603
TI  - Histologic assessment of dose-related diffusion and muscle fiber response after
      therapeutic botulinum A toxin injections.
AB  - Fiber diameter variability, acetylcholinesterase staining properties, and average
      fiber diameter were determined 5 weeks after varying doses of botulinum A toxin
      were administered into albino rabbit longissimus dorsi muscle. The average fiber
      diameter within the muscle appeared to be a function of the dose of botulinum
      toxin injected. Fiber diameter variability correlated with the dose of botulinum
      toxin administered. Both fiber diameter variability and acetylcholinesterase
      spread characteristics showed a distinct diffusion gradient over a defined field
      within a muscle. At lower doses (1 IU), collapse of the diffusion gradient
      occurred over a 15-30-mm segment of muscle. At higher doses (5-10 IU), diffusion
      of botulinum A toxin effect occurred throughout the entire muscle with no
      apparent end point. This study demonstrated that botulinum A toxin produces a
      gradient of denervation in a given muscle and that both the magnitude of
      denervation and the extent of the gradient are dose dependent. Furthermore, both
      muscle fiber diameter variability and acetylcholinesterase staining were useful
      as measures of chemodenervation.

PMID- 8139604
TI  - A multicenter double-blind placebo-controlled trial of pergolide as an adjunct to
      Sinemet in Parkinson's disease.
AB  - Three hundred and seventy-six subjects with advanced Parkinson's disease
      participated in a prospective, double-blind placebo-controlled study of the
      dopamine agonist pergolide mesylate as an adjunct to Sinemet. At 6 months,
      patients randomized to pergolide had a statistically significant improvement in
      total Parkinson's score, scores of activities of daily living, motor function,
      number of "off" hours, Hoehn and Yahr stage, and numerous parameters of
      parkinsonian function including bradykinesia, rigidity, gait, and dexterity. This
      benefit was obtained with the addition of a mean dose of 2.94 mg of pergolide,
      which permitted a 24.7% reduction in dose of levodopa. Adverse reactions were,
      for the most part, mild, reversible, and not of major clinical significance. No
      significant cardiac or electrocardiographic abnormalities were detected. This
      study demonstrates that pergolide mesylate, as an adjunct to levodopa, is an
      effective antiparkinsonian agent that provides clinical improvement while
      permitting a reduction in levodopa dose.

PMID- 8139605
TI  - Visual control of arm movement in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) are more dependent on visual information
      during movements than normals. To investigate the mechanisms underlying
      deterioration of movement under nonvisual conditions, we studied two-dimensional
      pointing movements to randomly occurring targets. The experimental design allowed
      us to systematically manipulate visual feedback during the movement by removing
      vision of the target, of the moving hand, or of both. Execution of pointing
      movements in PD deviated most severely from that of normals when PD patients
      moved without vision of their own moving hand. Under this condition,
      undershooting of the target appeared, and movements were particularly slow. In
      contrast, with complete vision or when only vision of the target was occluded,
      pointing movements of PD patients were accurate and faster. PD patients had no
      difficulties selecting the correct movement direction. Reaction times were longer
      in PD patients irrespective of the availability of visual feedback. Our findings
      suggest that the ability of PD patients to use nonvisual feedback during
      execution of arm movements is impaired.

PMID- 8139606
TI  - Variable onset of adult inherited focal dystonia: a problem for genetic studies.

PMID- 8139607
TI  - A case-control study of Parkinson's disease in a horticultural region of British
      Columbia.
AB  - We compared personal histories of 127 cases and 245 controls to identify possible
      environmental risk factors for idiopathic parkinsonism (IP). Of our controls, 121
      had cardiac disease (CD) and 124 were randomly selected from electoral lists
      (voters). Using logistic regression and adjusting for sex and age, we ran
      separate analyses: IP versus CD and IP versus voters. A full occupational history
      was collected, as was known contact with all pesticides associated with the tree
      fruit sector of the agricultural industry. We found a significant association
      between IP and having had an occupation in which exposure through handling or
      directly contacting pesticides was probable, but no specific chemicals were
      associated with IP. We conclude that although occupations involving the use of
      agricultural chemicals may predispose to the development of IP, it seems likely
      that the pathogenesis is multifactorial rather than related to a specific agent.

PMID- 8139608
TI  - Unified Parkinson's Disease Rating Scale characteristics and structure. The
      Cooperative Multicentric Group.
AB  - Our purpose was to verify some basic aspects of validation of the Unified
      Parkinson's Disease Rating Scale (UPDRS). One hundred and sixty-seven Parkinson's
      disease (PD) patients were included. Group A (n = 40) was simultaneously assessed
      by five raters who applied the UPDRS and other PD rating scales (PDRS). A set of
      timed tests, the Mini-Mental State Examination (MMSE), and the Hamilton Scale for
      Depression (HSD) were administered by an independent examiner. Group B (n = 127)
      was individually assessed through the UPDRS and the other PDRSs by one
      neurologist in four different hospitals. The UPDRS was administered in 16.95 +/-
      7.98 min. The internal consistency was high (Cronbach's alpha = 0.96).
      Nevertheless, the items related to depression, motivation/initiative, and tremor
      were scarcely consistent. The Interrater reliability was satisfactory (all the
      items had k > 0.40). There was a high correlation of the UPDRS with the Hoehn and
      Yahr staging (rs = 0.71; p < 0.001) and some timed tests (finger tapping; arising
      from chair), but also with the MMSE and HSD (rs = 0.53; rs = 0.64; p < 0.001).
      The convergent validity with the other PDRS (Intermediate Scale and Schwab and
      England Scale) was very high (rs = 0.76-0.96; p < 0.001). The factor analysis
      identified six factors that explained 59.6% of the variance. The dimension
      "tremor" showed a remarkable independence. The UPDRS is a multidimensional,
      reliable, and valid scale, with some inconveniences derived from its internal
      consistency, discriminant validity, and pragmatic application.

PMID- 8139609
TI  - Rating impairment and disability in Parkinson's disease: evaluation of the
      Unified Parkinson's Disease Rating Scale.
AB  - Although the Unified Parkinson's Disease Rating Scale (UPDRS) is widely used to
      monitor disease progression and drug efficacy, no attempts have been made to
      evaluate its scientific and clinical quality. Poor clinical sensibility of items
      in the activities of daily living (ADL) section and redundancy of items in the
      motor examination (ME) section prompted us to determine if the number of items in
      these sections could be reduced to a smaller, equally sensitive set that would
      describe the data as reliably as did the original set of items. Therefore, we
      assessed 111 patients with idiopathic Parkinson's disease on the UPDRS and Hoehn
      and Yahr staging scales. Our results show that the ADL (13 items) and ME (14
      items) sections can be reduced to 8 items each without loss of reliability or
      validity. Our report is preliminary and needs validation.

PMID- 8139610
TI  - Interrater reliability of the Unified Parkinson's Disease Rating Scale motor
      examination.
AB  - Interrater reliability of the Unified Parkinson's Disease Rating Scale (UPDRS)
      motor examination was assessed by three neurologists experienced in the
      administration of this scale. Intraclass correlation coefficients indicated good
      to-excellent agreement for speeded repeated movements, resting tremor, arising
      from a chair, and gait; moderate agreement for action tremor, rigidity, posture,
      postural stability, and bradykinesia; and poor agreement for speech disorder and
      facial immobility. Overall, these results indicate that satisfactory interrater
      reliability is attainable with the UPDRS motor examination.

PMID- 8139611
TI  - Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an
      HPLC and ESR study.
AB  - Previous studies examining the involvement of oxidative stress in the substantia
      nigra in Parkinson's disease have measured terminal products of lipid
      peroxidation or the function of antioxidant defense systems. We report a more
      specific early marker of lipid peroxidation, lipid hydroperoxides, in a high
      performance liquid chromatography (HPLC) and electron spin resonance (ESR)
      investigation. HPLC-chemiluminescent detection revealed two classes of lipid
      hydroperoxides in brain tissue extracts--free fatty acid hydroperoxides and
      cholesterol lipid hydroperoxides. Only cholesterol lipid hydroperoxides were
      consistently detected in all tissue extracts. Cholesterol lipid hydroperoxides
      had a 10-fold increase in the Parkinson's disease substantia nigra compared to
      control subjects. ESR detection of radical degradation products, including those
      of lipid hydroperoxides, in nigral homogenates incubated with the spin trap N-t
      butyl-alpha-phenyl nitrone (PBN) showed a marked variation in ESR signal between
      tissues. Despite the increased levels of lipid hydroperoxides in parkinsonian
      substantia nigra, there was no overall difference in ESR signal intensity between
      nigral tissues from controls and from patients with Parkinson's disease. The
      increased levels of an early component of the peroxidation chain in substantia
      nigra in Parkinson's disease support the hypothesis of a continuous toxic process
      involving oxygen radical activity. However, using previously frozen tissue, ESR
      evidence for increased radical formation could not be demonstrated.

PMID- 8139612
TI  - Posttraumatic paroxysmal nocturnal hemidystonia.
AB  - The term "nocturnal paroxysmal dystonia" has been used to describe patients who
      display paroxysmal episodes of dystonic-dyskinetic movements arising during
      nonrapid eye movement sleep, in particular stages 2-3 (Lugaresi E, Cirignotta F.
      Hypnogenic paroxysmal dystonia: epileptic seizure or a new syndrome. Sleep
      1981;4: 129-138). The pathogenesis of these attacks has remained controversial.
      We describe a patient with posttraumatic paroxysmal nocturnal hemidystonia.
      Acetazolamide led to improvement.

PMID- 8139613
TI  - Sequence diversity and organization of the msp gene family encoding gp63 of
      Leishmania chagasi.
AB  - During in vitro growth Leishmania chagasi promastigotes differentially express 3
      classes of RNAs encoding the major surface protease (MSP) gp63 that can be
      distinguished by their unique 3' untranslated regions. Here we show that the
      three classes (logarithmic-specific, stationary-specific and constitutively
      expressed) are encoded by a family of at least 4 tandem stationary genes (mspS2,
      mspS1, mspS3 and mspS5) followed by twelve or more logarithmic genes (mspL
      genes), one constitutive gene (mspC) and a final stationary gene (mspS4). Some of
      the stationary genes can be distinguished from each other by groups of nucleotide
      differences within the coding regions that result in localized amino acid
      differences. Northern blots confirm that RNAs from the individual stationary
      genes are present in stationary, but not logarithmic, phase promastigotes.
      Western blots using sera directed against synthetic peptides indicate that
      correspondingly heterogeneous gp63 proteins are expressed in L. chagasi
      promastigotes. A 200-bp region upstream of all three gp63 gene classes is
      conserved except for a variable number of 6-bp repeats. Downstream of the gp63
      coding regions are highly conserved, class-specific sequences that include the 3'
      untranslated regions and extend past the polyadenylation site for 65 bp (mspL),
      345 bp (mspC) or 2.8 kb (mspS). These sequence features flanking the msp coding
      regions are likely important in the growth phase-specific expression of the three
      gp63 RNA classes.

PMID- 8139614
TI  - Sequence and genomic organization of the hsp70 genes of Leishmania amazonensis.
AB  - The sequence and genomic organization of hsp70 genes in Leishmania amazonensis
      were examined. Maps of overlapping cosmid clones revealed that seven L.
      amazonensis hsp70 genes are organized into a 24-kb locus containing 3.5-kb tandem
      repeats. Cosmids covering a different chromosomal region indicated that an eighth
      hsp70 sequence is located at a distant site. Southern blot data suggested the
      existence of additional hsp70 genes or pseudogenes. One complete 3.5-kb genomic
      repeat unit, including coding and intergenic regions, was sequenced. The
      predicted L. amazonensis HSP70 protein had approximately 95% sequence identity
      with Leishmania donovani or Leishmania major HSP70, 81-85% identity with
      trypanosome HSP70, and 68 or 72% identity with human HSP70 or HSP70 cognate,
      respectively. The GGMP tetrapeptide repeat found in other trypanosomatid HSP70
      proteins is absent from the L. amazonensis sequence. Intergenic sequences of L.
      amazonensis and L. major differed mainly in the presence of short gaps in the L.
      amazonensis sequence. Potential regulatory heat shock elements were identified in
      the upstream sequence. Several cDNA clones were also isolated, and two different
      poly(A) addition sites 100 nucleotides apart were identified.

PMID- 8139615
TI  - Characterisation of two soluble metalloexopeptidases in the protozoan parasite
      Leishmania major.
AB  - Two soluble exopeptidases were identified in promastigotes of Leishmania major,
      using an iodinated model tetrapeptide (LIAY) as substrate. Similar activities
      were also detected in L. major amastigotes and in different species of Leishmania
      promastigotes. A carboxy- and an aminopeptidase activity were resolved and
      isolated by anion exchange and gel permeation chromatographies. A single
      polypeptide of 62 kDa co-purified with the aminopeptidase activity. Optimum pH
      was neutral for the carboxypeptidase and neutral to alkaline for the
      aminopeptidase. Both activities were able to hydrolyse a dipeptide substrate
      (YL), and were inhibited by 20 microM bestatin and 200 microM 1,10
      phenanthroline, but not by leupeptin, iodoacetamide and a range of other
      inhibitors. These results strongly suggest that both enzymes are
      metalloexopeptidases and thus represent a novel class of soluble peptidases in
      Leishmania.

PMID- 8139616
TI  - Proteolytic digestion of band 3 at an external site alters the erythrocyte
      membrane organisation and may facilitate malarial invasion.
AB  - Invasion of human erythrocytes by Plasmodium falciparum is inhibited by
      chymostatin. This suggests that digestion of erythrocyte surface proteins by a
      protease with chymotrypsin-like activity may be involved in the invasion process.
      We find that treatment of intact erythrocytes with chymotrypsin cleaves the
      integral membrane protein, band 3, generating a major fragment with an apparent
      molecular weight of 58 kDa. We have used measurements of the rotational mobility
      of band 3, labelled with the phosphorescence probe, eosin-5-maleimide, as a
      monitor of the changes in the molecular organisation of the erythrocyte membrane
      which accompany band 3 cleavage. We report that the chymotrypsin treatment
      increases the rotational freedom of band 3, possibly due to conformational
      changes which disrupt its interaction with the underlying peripheral membrane
      proteins. We also show that chymotrypsin-treated erythrocytes undergo extensive
      endocytosis upon incorporation of exogenous fluorescently labelled phospholipid.
      We suggest that during the invasion process, digestion of band 3 by a
      chymotrypsin-like protease may induce a localised disruption of the erythrocyte
      membrane. This destabilised region of membrane may represent the site for the
      insertion of parasite-derived phospholipid, thus allowing the formation of the
      parasitophorous vacuole membrane.

PMID- 8139617
TI  - Mutational analysis of a signal sequence required for protein secretion in
      Leishmania major.
AB  - In eukaryotes, amino-terminal extensions, signal sequences, mediate the
      translocation of lysosomal, membrane and secreted proteins into the lumen of the
      endoplasmic reticulum (ER). Structure/function studies indicate that eukaryotic
      signal sequences are composed of 3 distinct domains, a positively charged amino
      terminal domain, a central hydrophobic domain, and a polar carboxy-terminal
      domain. In an attempt to better understand protein trafficking in Leishmania we
      have constructed strains of Leishmania major that secrete an exogenous protein,
      interferon-gamma (IFN-gamma), under the control of a mammalian signal sequence.
      In this report we present a mutational analysis of this signal sequence. Deletion
      of the entire signal sequence or the hydrophobic core region prevents secretion
      of IFN-gamma and results in cytoplasmic expression of the protein. Mutations in
      the amino-terminal domain indicate that a net positive charge is not required for
      efficient secretion of IFN-gamma. Mutations in the carboxy-terminal domain are
      more complex and display two phenotypes, either they prevent expression of IFN
      gamma or they have no effect on protein secretion. These results indicate that
      the function of the signal sequence in targeting proteins to the ER in Leishmania
      is similar to that observed in yeasts and higher eukaryotes and suggests that the
      Leishmania protein secretory apparatus may also be similar.

PMID- 8139618
TI  - Proton NMR lipid profile of Leishmania donovani promastigotes.
AB  - The proton nuclear magnetic resonance (NMR) lipid profile of Leishmania donovani
      was obtained in the one-dimensional and two-dimensional modes. Partial
      assignments of lipid classes and individual lipids were obtained purely from the
      proton NMR spectrum of the mixture. A more complete assignment and quantitative
      analysis was achieved by prior separation of the lipids by high pressure liquid
      chromatography (HPLC) followed by proton NMR analysis of the fractions. This work
      showed that proton NMR spectroscopy could facilitate lipid analysis and
      classification of various parasitic protozoa and serve as a basis for rapid
      studies of comparative lipid metabolism in parasites.

PMID- 8139619
TI  - A Plasmodium chabaudi antigen located in the parasitophorous vacuole membrane.
AB  - In order to study antigens from the rodent malaria Plasmodium chabaudi, clones
      reacting with mouse hyperimmune serum were selected from an expression library of
      blood-stage P. chabaudi cDNAs in the vector pGEX-2T. Sixty-four such clones were
      shown to derive from 19 different P. chabaudi antigens. One of these, Antigen
      3008 (Ag3008), has a predicted size of 17.5 kDa and an observed size of 24 kDa.
      It is located in the parasitophorous vacuole membrane of maturing parasites and
      in the dense granules of merozoites. The cDNA sequence predicts a highly charged
      molecule with an N-terminal signal sequence and a central transmembrane domain,
      but no tandem repeats. The sequence reported for Pc24, a previously identified
      but uncharacterized P. chabaudi protein, corresponds to part of the 3'
      untranslated region in the Ag3008 mRNA. Ag3008 has many features in common with
      the P. falciparum circumsporozoite protein-related antigen (CRA).

PMID- 8139620
TI  - Cathepsin B-like cysteine proteases of Leishmania mexicana.
AB  - A group of Leishmania mexicana cysteine proteases that differ from those
      previously found in this protozoon are described. The enzymes characteristically
      have a preference for peptidyl substrates with a phenylalanyl-valyl-arginyl
      moiety, do not hydrolyse gelatin in substrate-sodium dodecyl sulphate
      polyacrylamide gels, are stimulated by thiol-reducing agents and are sensitive to
      inhibitors specific for cysteine proteases. They have unusual solubility
      properties that indicate that the enzymes are amphiphilic proteins. Two of the
      cysteine proteases have been purified from L. mexicana amastigotes and shown to
      have molecular masses of 31 and 33 kDa. Their N-terminal amino acid sequences are
      very similar and show high homology to the mammalian cysteine protease, cathepsin
      B.

PMID- 8139621
TI  - Expression of cloned beta-tubulin genes of Haemonchus contortus in Escherichia
      coli: interaction of recombinant beta-tubulin with native tubulin and
      mebendazole.
AB  - Two distinct beta-tubulin cDNA isotypes (beta 8-9 and beta 12-16) from Haemonchus
      contortus were expressed for the first time in Escherichia coli and characterised
      by their specific mebendazole (MBZ) binding and polymerization properties. Beta
      tubulin was expressed without translational fusion to an E. coli sequence under
      the regulation of the tryptophan promoter in the pTrp2 vector. Beta-tubulin was
      produced in large amounts in insoluble 'inclusion bodies'. The inclusion bodies
      were purified and solubilised and the beta-tubulin renatured by treatment with
      urea followed by dilution with alkaline buffer and a shift to physiological pH.
      The yield was more than 10 mg of beta-tubulin per litre of cell culture. The
      recombinant tubulin produced was recognized in Western blot by specific anti-beta
      tubulin antibodies. Tritiated MBZ binding to the recombinant H. contortus beta
      tubulin was measured in the presence or absence of whole, tubulin-free or tubulin
      rich extracts of H. contortus. Some [3H]MBZ high-affinity binding (HB) to 'pure'
      (no other eukaryotic protein present) beta 8-9 or beta 12-16 was observed.
      Enhanced high-affinity binding was observed when recombinant beta 8-9 or beta 12
      16 were mixed and pre-incubated with whole supernatants or tubulin-enriched
      extracts from H. contortus. The enhancement was more than additive. Beta 12-16
      bound more MBZ and caused a greater enhancement than beta 8-9. Mixing recombinant
      beta 8-9 or beta 12-16 with whole supernatants or tubulin-enriched fractions from
      H. contortus promoter polymerization at 37 degrees C. Use of 35S-labelled protein
      showed that the polymer contained recombinant tubulin. Western blot using
      specific anti-alpha-tubulin monoclonal antibodies showed that the polymer
      contained alpha-tubulin. Similarly the recombinant nematode beta-tubulin co
      polymerized with tubulin from chicken brain. Our data suggest that the
      recombinant beta-tubulin can interact and copolymerize with parasite or chicken
      tubulin. Furthermore the interaction of recombinant nematode beta-tubulin with
      native tubulin and/or microtubule associated proteins (MAPs) resulted in the
      formation of high-affinity MBZ-binding sites. However, interaction of recombinant
      beta-tubulin with microtubule proteins from chicken brain did not result in the
      formation of high-affinity MBZ-binding sites.

PMID- 8139622
TI  - Cloning and characterization of an Eimeria acervulina sporozoite gene homologous
      to aspartyl proteinases.
AB  - A lambda ZapII cDNA library was constructed using mRNA from Eimeria acervulina
      sporulated oocysts and screened with monoclonal antibodies raised against Eimeria
      tenella sporulated oocytes. Monoclonal antibody N3C8B12 identified a clone (6S2)
      potentially encoding an aspartyl proteinase since significant homology with
      cathepsin D, pepsin and renin proteinases was revealed by sequence comparisons.
      The 1500-bp cDNA fragment containing the coccidial gene was subcloned into pGEX
      FA expression vector, leading to the production of an 80-kDa fusion protein
      (FA6S2) which was used to immunize rabbits. The anti-FA6S2 rabbit sera revealed a
      single 43-kDa protein present in Eimeria acervulina, Eimeria tenella, Eimeria
      maxima and Eimeria falciformis sporulated oocyst antigens. Indirect
      immunofluorescence and electron microscopy with mAb N3C8B12 localized the
      putative aspartyl proteinase in the refractile bodies of Eimeria tenella
      sporozoites.

PMID- 8139623
TI  - Cloning and sequencing of the gene encoding Schistosoma mansoni calreticulin.

PMID- 8139624
TI  - Molecular cloning and sequencing of hsp70 cDNA of Theileria sergenti.

PMID- 8139625
TI  - Nucleotide sequence of a minicircle from Leishmania infantum.

PMID- 8139626
TI  - Identification of a histone H1-like gene expressed in Leishmania major.

PMID- 8139627
TI  - The effect of epoetin beta (recombinant human erythropoietin) on the need for
      transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin
      Study Group.
AB  - BACKGROUND: Anemia of prematurity is characterized by low reticulocyte counts and
      inadequate erythropoietin response, for which many very-low-birth-weight infants
      receive multiple blood transfusions. We investigated whether early treatment of
      such infants with recombinant human erythropoietin would reduce their need for
      transfusions. METHODS: We performed a controlled, blinded trial in 241 infants
      with very low birth weights at 12 centers in six European countries. When three
      days old, the infants were randomly assigned either to the epoetin group or to
      the control group. Those in the epoetin group received 250 IU of epoetin beta per
      kilogram of body weight subcutaneously three times a week from day 3 to day 42
      (for a total of 17 doses); those in the control group did not receive this drug.
      Infants in both groups received oral iron (2 mg per day) from day 14 onward.
      RESULTS: The control infants needed a mean of 1.25 transfusions each, as compared
      with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median
      cumulative volume of blood transfused per kilogram per day was 0.41 ml in the
      control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the
      epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The
      rate of success, defined as an absence of need for transfusions and a hematocrit
      that never fell below 32 percent, was 4.1 percent in the control group and 27.5
      percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys
      with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or
      more. No toxic effects were observed in the epoetin group; as compared with the
      control group, the epoetin group had an increased incidence of septicemia (14 vs.
      7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02).
      CONCLUSIONS: Infants with very low birth weights have less need of transfusions
      if given epoetin beta during the first six weeks of life (250 IU per kilogram
      three times a week). We recommend early epoetin treatment for all such infants,
      but further studies of nutrition and iron supplementation during treatment are
      needed.

PMID- 8139628
TI  - The effect of directly observed therapy on the rates of drug resistance and
      relapse in tuberculosis.
AB  - BACKGROUND: Tuberculosis has reemerged as an important public health problem, and
      the frequency of drug resistance is increasing. A major reason for the
      development of resistant infections and relapse is poor compliance with medical
      regimens. In Tarrant County, Texas, we initiated a program of universal directly
      observed treatment for tuberculosis. We report the effect of the program on the
      rates of primary and acquired drug resistance and relapse among patients with
      tuberculosis. METHODS: We collected information on all patients with positive
      cultures for Mycobacterium tuberculosis in Tarrant County from January 1, 1980,
      through December 31, 1992. Through October 1986, patients received a traditional,
      unsupervised drug regimen. Beginning in November 1986, nearly all patients
      received therapy under direct observation by health care personnel. RESULTS: A
      total of 407 episodes in which patients received traditional treatment for
      tuberculosis (January 1980 through October 1986) were compared with 581 episodes
      in which therapy was directly observed (November 1986 through December 1992).
      Despite higher rates of intravenous drug use and homelessness and an increasing
      rate of tuberculosis during this 13-year period, the frequency of primary drug
      resistance decreased from 13.0 percent to 6.7 percent (P < 0.001) after the
      institution of direct observation of therapy, and the frequency of acquired
      resistance declined from 14.0 percent to 2.1 percent (P < 0.001). The relapse
      rate decreased from 20.9 percent to 5.5 percent (P < 0.001), and the number of
      relapses with multidrug-resistant organisms decreased from 25 to 5 (P < 0.001).
      CONCLUSIONS: The administration of therapy for M. tuberculosis infection under
      direct observation leads to significant reductions in the frequency of primary
      drug resistance, acquired drug resistance, and relapse.

PMID- 8139629
TI  - Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte
      P antigen).
AB  - BACKGROUND: The presence of a specific cellular receptor is thought to be
      necessary for susceptibility to viral infection. The erythrocyte P antigen is the
      cellular receptor for parvovirus B19. We hypothesized that the rare persons with
      the p phenotype, whose erythrocytes do not have this receptor, would be naturally
      resistant to B19 infection, which causes erythema infectiosum. METHODS: Blood
      samples were collected from two populations in cross-sectional studies. We
      determined the P antigen phenotype of the red cells and tested plasma for anti
      B19-specific antibodies. Bone marrow from donors of known P antigen phenotype was
      inoculated with parvovirus B19. Infectivity was measured by assays of erythroid
      progenitor cells, dot blot analysis, and in situ hybridization for B19 DNA, and
      an immunofluorescence assay for viral-capsid proteins. RESULTS: Of the 17
      subjects with the p red-cell phenotype, who did not have P antigen on their
      erythrocytes, none (0 of 11 and 0 of 6) had serologic evidence of previous
      parvovirus B19 infection. In contrast, the seropositivity rates in the two
      control groups were 71 percent (53 of 75, P < 0.001) and 47 percent (32 of 68, P
      = 0.03). In vitro, bone marrow from donors with the p phenotype maintained normal
      erythropoiesis despite very high concentrations of virus, with no evidence of
      infection of erythroid progenitor cells by parvovirus B19. CONCLUSIONS: People
      who do not have P antigen, which is the cellular receptor for parvovirus B19, are
      naturally resistant to infection with this pathogen.

PMID- 8139630
TI  - Images in clinical medicine. Progressive multifocal leukoencephalopathy.

PMID- 8139631
TI  - Right ventricular infarction.
AB  - Right ventricular infarction complicates up to half of inferior left ventricular
      infarctions. The term represents a spectrum of disease from mild, asymptomatic
      right ventricular dysfunction to cardiogenic shock, and it includes transient
      ischemic myocardial dysfunction as well as myocardial necrosis. Right ventricular
      infarction is associated with considerable morbidity and mortality, and its
      presence defines a high-risk subgroup of patients with inferior left ventricular
      infarction. Diagnosis of this condition requires a high degree of suspicion based
      on clinical findings and the early recording of the electrocardiogram through
      right precordial leads, as well as elevated right-sided filling pressures out of
      proportion to left-sided filling pressures. The proper management of right
      ventricular infarction requires sustaining adequate right ventricular preload
      with volume loading and maintenance of atrioventricular synchrony, reduction of
      right ventricular afterload (particularly when left ventricular dysfunction is
      present), and inotropic support of the right ventricle. Early reperfusion with
      fibrinolytic therapy or direct angioplasty is also warranted. Survivors of right
      ventricular infarction generally have a restoration of normal right ventricular
      function with resolution of hemodynamic abnormalities.

PMID- 8139632
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 17-1994. A 38-year-old man with AIDS, sudden abdominal pain, and
      bleeding from the rectum.

PMID- 8139633
TI  - Erythropoietin and neonatal anemia.

PMID- 8139634
TI  - Can antibiotic resistance be controlled?

PMID- 8139635
TI  - Using T cells to treat B-cell cancers.

PMID- 8139636
TI  - Viability of infants born at 22 to 25 weeks' gestation.

PMID- 8139637
TI  - Viability of infants born at 22 to 25 weeks' gestation.

PMID- 8139638
TI  - Viability of infants born at 22 to 25 weeks' gestation.

PMID- 8139639
TI  - The malpractice mess.

PMID- 8139641
TI  - The malpractice mess.

PMID- 8139640
TI  - The malpractice mess.

PMID- 8139642
TI  - Air pollution and mortality.

PMID- 8139643
TI  - Corticosteroids, optic neuritis, and multiple sclerosis.

PMID- 8139644
TI  - Corticosteroids, optic neuritis, and multiple sclerosis.

PMID- 8139645
TI  - Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia.

PMID- 8139646
TI  - Escherichia coli resistant to fluoroquinolones in patients with cancer and
      neutropenia.

PMID- 8139647
TI  - Limited tolerance of ofloxacin and pyrazinamide prophylaxis against tuberculosis.

PMID- 8139648
TI  - Alcohol intake and risk of myocardial infarction.

PMID- 8139649
TI  - Alcohol intake and risk of myocardial infarction.

PMID- 8139650
TI  - Multiple-antibiotic-resistant pathogenic bacteria. A report on the Rockefeller
      University Workshop.

PMID- 8139651
TI  - Neurobiology. Just a chemical attraction.

PMID- 8139652
TI  - Similarity of met and trp repressors.

PMID- 8139653
TI  - Single myosin molecule mechanics: piconewton forces and nanometre steps.
AB  - A new in vitro assay using a feedback enhanced laser trap system allows direct
      measurement of force and displacement that results from the interaction of a
      single myosin molecule with a single suspended actin filament. Discrete stepwise
      movements averaging 11 nm were seen under conditions of low load, and single
      force transients averaging 3-4 pN were measured under isometric conditions. The
      magnitudes of the single forces and displacements are consistent with predictions
      of the conventional swinging-crossbridge model of muscle contraction.

PMID- 8139654
TI  - Protein-protein interactions and 5'-splice-site recognition in mammalian mRNA
      precursors.
AB  - Exactly how specific splice sites are recognized during the processing of complex
      precursor messenger RNAs is not clear. Small nuclear ribonucleoprotein particles
      (snRNPs) are involved, but are not sufficient by themselves to define splice
      sites. Now a human protein essential for splicing in vitro, called alternative
      splicing factor/splicing factor 2, is shown to cooperate with the U1 snRNP
      particle in binding pre-mRNA. This cooperation is probably achieved by specific
      interactions between the arginine/serine-rich domain of the splicing factor and a
      similar region in a U1 snRNP-specific protein.

PMID- 8139655
TI  - Turning of nerve growth cones induced by neurotransmitters.
AB  - Pathfinding by growing nerve processes in the developing nervous system depends
      on the turning response of the growing tip, the growth cone, to extracellular
      guidance cues. There is evidence in vivo and in cell culture that some growth
      cones exhibit chemotropic behaviour, but the identity of endogenous
      chemoattractants remains elusive. Neurotransmitters appear early in the
      developing embryo and may have morphogenic roles in development. In cell culture
      a number of neurotransmitters were found to induce growth inhibition or
      retraction of neurites. Here we report positive turning responses of the nerve
      growth cone in a defined extracellular gradient of the neurotransmitter
      acetylcholine (ACh). The growth cone response depends on the activation of
      neuronal nicotinic ACh receptors, requires the presence of extracellular Ca2+,
      and appears to be mediated by Ca(2+)-calmodulin-dependent protein kinase II.
      Fluorescence imaging of cytosolic Ca2+ concentration ([Ca2+]i) at the growth cone
      showed a small but significant evaluation of [Ca2+]i within minutes of the onset
      of ACh application and before the turning of the growth cone. These findings
      suggest that neurotransmitters may serve as specific chemoattractants for growth
      cone guidance and that cytosolic Ca2+ may act as a second messenger in the
      cytoplasm of the growth cone to initiate the turning response.

PMID- 8139656
TI  - Changing subunit composition of heteromeric NMDA receptors during development of
      rat cortex.
AB  - Activation of the N-methyl-D-aspartate (NMDA) receptor is important for certain
      forms of activity-dependent synaptic plasticity, such as long-term potentiation
      (reviewed in ref. 1), and the patterning of connections during development of the
      visual system (reviewed in refs 2, 3). Several subunits of the NMDA receptor have
      been cloned: these are NMDAR1 (NR1), and NMDAR2A, 2B, 2C and 2D (NR2A-D). Based
      on heterologous co-expression studies, it is inferred that NR1 encodes an
      essential subunit of NMDA receptors and that functional diversity of NMDA
      receptors in vivo is effected by differential incorporation of subunits NR2A
      NR2D. Little is known, however, about the actual subunit composition or
      heterogeneity of NMDA receptors in the brain. By co-immunoprecipitation with
      subunit-specific antibodies, we present here direct evidence that NMDA receptors
      exist in rat neocortex as heteromeric complexes of considerable heterogeneity,
      some containing both NR2A and NR2B subunits. A progressive alteration in subunit
      composition seen postnatally could contribute to NMDA-receptor variation and
      changing synaptic plasticity during cortical development.

PMID- 8139657
TI  - Mice lacking brain-derived neurotrophic factor develop with sensory deficits.
AB  - During vertebrate development, neuronal survival depends on target-derived
      neurotrophic factors. Brain-derived neurotrophic factor (BDNF), a member of the
      neurotrophin family, can prevent the death of particular peripheral sensory
      neurons in vitro, and of central motor neurons as well as dopaminergic and
      cholinergic neurons of the basal forebrain during development. It also prevents
      the death of motor neurons and midbrain dopaminergic neurons induced by lesions.
      Here we show that mutant mice lacking BDNF have severe deficiencies in
      coordination and balance, associated with excessive degeneration in several
      sensory ganglia including the vestibular ganglion. The few remaining vestibular
      axons fail to contact the vestibular sensory epithelia, and terminate in the
      adjacent connective tissue. Survival of sympathetic, midbrain dopaminergic and
      motor neurons is not affected. These results indicate that BDNF is required for
      the survival and target innervation of particular neuronal populations.

PMID- 8139658
TI  - Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta
      and Serrate of Drosophila.
AB  - The lin-12 and glp-1 genes of Caenorhabditis elegans encode members of the Notch
      family of transmembrane proteins. Genetic studies indicate that the lin-12 and
      glp-1 proteins act as receptors in specific developmental cell interactions and
      that their functions are partially redundant. lin-12 glp-1 double mutants display
      certain embryonic defects not found in either single mutant. The phenotype of
      this double mutant is called Lag, and recessive mutations in either of the genes
      lag-1 or lag-2 can also result in the Lag phenotype, indicating that these two
      genes may participate in the same cell interactions that require lin-12 or glp-1.
      We report here that lag-2 encodes a predicted transmembrane protein of 402 amino
      acids. The predicted extracellular region of lag-2 is similar to amino-terminal
      regions of Delta and Serrate, two Drosophila proteins that are thought to
      function as ligands for Notch. The region of similarity includes sequences
      related to epidermal growth factor (EGF) repeats. We have isolated lag2(sa37), a
      dominant allele that shows specific genetic interactions with lin-12. The sa37
      mutation causes a Gly-->Asp change in a conserved residue of an EGF motif.
      Because of its overall structure, its sequence similarity to Delta and Serrate,
      and its genetic interactions, we suggest that lag-2 encodes an intercellular
      signal for the lin-12 and glp-1 receptors.

PMID- 8139659
TI  - The human X-inactivation centre is not required for maintenance of X-chromosome
      inactivation.
AB  - X-chromosome inactivation occurs early in mammalian female development to achieve
      dosage compensation with males. Although it is widely accepted that this
      inactivation requires the presence in cis of the X-inactivation centre (XIC), it
      is not known whether the XIC is required for the initiation, promulgation or
      maintenance of X inactivation. The XIST gene, which is localized within the XIC
      interval on both the human and mouse X chromosomes, is constitutively expressed
      from inactive X chromosomes, suggesting a possible role in the maintenance of X
      inactivation. To address whether the presence of the XIC, including the XIST
      gene, is continuously required for the maintenance of X-chromosome inactivation,
      we have analysed the transcriptional activity of a number of X-linked genes in
      mouse/human somatic cell hybrids retaining an intact human inactive X chromosome
      or derivatives of the inactive X chromosome lacking the XIC. Genes subject to X
      inactivation remain transcriptionally silent despite the loss of the XIC,
      demonstrating that the presence of the XIC is not required for the maintenance of
      X inactivation in somatic cells.

PMID- 8139660
TI  - Membrane association of Rab5 mediated by GDP-dissociation inhibitor and
      accompanied by GDP/GTP exchange.
AB  - The Rab GTPases function as specific regulators of membrane transport. The
      GTP/GDP cycle is believed to control shuttling of Rab proteins between the
      cytosol and organelle membranes. In vitro, Rab proteins are removed from
      membranes by a protein that inhibits GDP dissociation (rabGDI), which leads to
      formation of a cytosolic complex of Rab with the inhibitor protein. Here we use a
      purified Rab5-rabGDI complex in a permeabilized cell system to investigate how
      the cytosolic complexed form of Rab reassociates with the membrane. We find that
      exogenous Rab5 is correctly targeted and induces the formation of enlarged early
      endosomes, demonstrating that it is functionally active. Binding of Rab5 to the
      acceptor membrane is accompanied by release of the rabGDI protein into the
      cytosol. A transient GDP-Rab5 intermediate was detected which was subsequently
      converted into the GTP-bound form. Our results indicate that there is a multistep
      mechanism for the insertion of Rab5 into the membrane which is mediated by a
      guanine-nucleotide-exchange factor.

PMID- 8139661
TI  - Detection of localized DNA flexibility.
AB  - The bending and flexibility of DNA are important in packaging, recombination and
      transcription. Bending decreases electrophoretic mobility in a manner depending
      on bend position within a fragment (circular permutation) and on the distance
      between bends (phasing analysis). Bending can also affect DNA ring closure
      (cyclization). The lack of a complete theory for the mechanism of gel retardation
      hampers measurement of bend magnitudes by electrophoresis, whereas cyclization is
      done entirely in solution and is well understood theoretically. Disagreements
      between bend angles estimated by the two electrophoretic assays have been
      ascribed to DNA flexibility. Here we test this interpretation using an internal
      loop as a model flexible locus. Whereas the circular permutation and helical
      phasing experiments are only subtly affected by the loop, DNA cyclization
      kinetics detects and quantifies substantial increases in torsional and bending
      flexibility. Furthermore, the results support a functional role for the stress of
      DNA bending in inducing base-pair opening.

PMID- 8139662
TI  - FDA lights smoking fire.

PMID- 8139663
TI  - Animals in research.

PMID- 8139664
TI  - Cancer geneticists sign deal with genome company.

PMID- 8139666
TI  - Protests challenge INSERM decision on Benveniste lab.

PMID- 8139665
TI  - Warning on cancer gene screening.

PMID- 8139668
TI  - Of sound mind.

PMID- 8139667
TI  - Pope to appoint bio-ethics committee.

PMID- 8139669
TI  - Don't call us...

PMID- 8139670
TI  - Towards more measurement in biology.

PMID- 8139671
TI  - Molecular architecture. Towards synthetic enzymes.

PMID- 8139672
TI  - Lung cancer. Radon risk reassessed.

PMID- 8139673
TI  - Molecular motors. Clamping down on myosin.

PMID- 8139674
TI  - Fatal blast at experimental reactor.

PMID- 8139675
TI  - Germans face yet tighter rules on lab animals.

PMID- 8139676
TI  - French research moves to meet public needs.

PMID- 8139677
TI  - French blood test.

PMID- 8139678
TI  - Smallpox bargain.

PMID- 8139679
TI  - Sexual selection. Swordplay and sensory bias.

PMID- 8139680
TI  - Cancer vaccination. Politically incorrect viruses.

PMID- 8139681
TI  - Vision. Improbable views.

PMID- 8139682
TI  - Statistical scrotal effect.

PMID- 8139683
TI  - Stomach NO synthesis.

PMID- 8139684
TI  - Viral-induced extinctions unlikely.

PMID- 8139685
TI  - Promoter targeting by adenovirus E1a through interaction with different cellular
      DNA-binding domains.
AB  - A puzzling property of the transcriptional activators encoded by several animal
      viruses is their ability to function promiscuously. The adenovirus E1a protein,
      for example, stimulates transcription of adenoviral genes as well as a wide
      variety of other viral and cellular genes. We show that E1a can interact with
      several classes of cellular DNA-binding domains and thereby be recruited to
      diverse promoters. Our results explain how a single protein can regulate
      transcription of multiple genes that lack a common promoter element.

PMID- 8139686
TI  - Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from
      a molecular phylogeny.
AB  - Darwin believed that sexual selection accounts for the evolution of exaggerated
      male ornaments, such as the sword-like caudal fin extensions of male fishes of
      the genus Xiphophorus, that appear detrimental to survival. Swordtails continue
      to feature prominently in empirical work and theories of sexual selection; the
      pre-existing bias hypothesis has been offered as an explanation for the evolution
      of swords in these fishes. Based upon a largely morphological phylogeny, this
      hypothesis suggests that female preference to mate with sworded males arose in
      ancestrally swordless species, thus pre-dating the origin of the sword itself and
      directly driving its evolution. Here we present a molecular phylogeny (based on
      mitochondrial and nuclear DNA sequences) of Xiphophorus which differs from the
      traditional one: it indicates that the sword originated and was lost repeatedly.
      Our phylogeny suggests that the ancestor of the genus is more likely to have
      possessed a sword than not, thus questioning the applicability of the pre
      existing bias hypothesis as an explanation for the evolution of this sexually
      selected trait.

PMID- 8139687
TI  - The generic viewpoint assumption in a framework for visual perception.
AB  - A visual system makes assumptions in order to interpret visual data. The
      assumption of 'generic view' states that the observer is not in a special
      position relative to the scene. Researchers commonly use a binary decision of
      generic or accidental view to disqualify scene interpretations that assume
      accidental viewpoints. Here we show how to use the generic view assumption, and
      others like it, to quantify the likelihood of a view, adding a new term to the
      probability of a given image interpretation. The resulting framework better
      models the visual world and reduces the reliance on other prior assumptions. It
      may lead to computer vision algorithms of greater power and accuracy, or to
      better models of human vision. We show applications to the problems of inferring
      shape, surface reflectance properties, and motion from images.

PMID- 8139688
TI  - Ventralizing signal determined by protease activation in Drosophila
      embryogenesis.
AB  - Specification of dorsal-ventral cell fate during Drosophila embryogenesis is
      mediated by a signal transduction pathway. Asymmetry of cell fates arises through
      the spatially restricted production of a ligand in an extracellular compartment
      called the perivitelline space. The snake and easter genes are required for the
      production of the ligand and they encode the proenzyme form of secreted
      extracellular serine proteases. We have examined the effect of producing a
      preactivated form of the snake protease on the generation of dorsal-ventral
      polarity. SP6 RNA microinjection experiments reveal that different cell fates
      acquired at cellular blastoderm can be specified by the amount and spatial
      distribution of activated snake protein. Our results support a protease cascade
      model in which localized activation of uniformly distributed protease proenzymes
      leads to the spatially restricted production of ligand in the perivitelline space
      on the ventral side of the embryo.

PMID- 8139689
TI  - An essential role for HLA-DM in antigen presentation by class II major
      histocompatibility molecules.
AB  - In antigen-presenting cells, class II molecules of the major histocompatibility
      complex (MHC) bind peptides derived from endocytosed proteins. In certain B
      lymphoblastoid cell mutants, MHC class II molecule-peptide complex formation is
      impaired, resulting in deficient antigen-presenting function. MHC deletion
      mutants with this defect map the responsible gene(s) to the class II region of
      the MHC. Here we report that multiple independent mutants with the class II
      presentation defect harbour lesions in HLA-DMB, an MHC-linked gene encoding a
      class II-like beta-chain. Expression of DMB complementary DNA in mutants lacking
      DMB messenger RNA restores the wild-type phenotype. These results establish HLA
      DM as a critical regulatory molecule in class II-restricted antigen presentation
      and suggest that it functions at an intracellular site to promote class II
      molecule-peptide association.

PMID- 8139690
TI  - HLA-DMA and -DMB genes are both required for MHC class II/peptide complex
      formation in antigen-presenting cells.
AB  - Major histocompatibility complex (MHC) class II molecules are highly polymorphic
      cell-surface glycoproteins that present antigenic peptides to CD4+ T lymphocytes.
      The normal assembly of class II molecules with cognate peptides for antigen
      presentation requires an accessory function provided by a gene mapping to the
      class II region of the HLA complex. The isolation of somatic cell mutants of
      antigen-presenting cells (APC) has shown that at least one gene which maps
      between HLA-DP and HLA-DQ, provisionally designated c2p-1 (ref. 3), mediates this
      process. Here we describe a unique new mutant 2.2.93, which manifests defective
      formation of class II/peptide complexes like that described in c2p-1 mutants. We
      show that (1) mutant 2.2.93 contains a mutation in HLA-DMA, and a representative
      c2p-1 mutant, 9.5.3, contains a mutation in HLA-DMB; and (2) transfection and
      expression of DMA complementary DNA in 2.2.93, and DMB cDNA in 9.5.3, reverses
      their mutant phenotypes. These results show that HLA-DMA and -DMB, genes of
      previously unknown function mapping between HLA-DP and HLA-DQ, are required for
      the normal assembly of peptides with MHC class II molecules. They suggest that
      HLA-DMA and -DMB encode subunits of a functional heterodimer which is critical in
      the pathway of class II antigen presentation.

PMID- 8139691
TI  - B61 is a ligand for the ECK receptor protein-tyrosine kinase.
AB  - A protein ligand for the ECK receptor protein-tyrosine kinase has been isolated
      by using the extracellular domain (ECK-X) of the receptor as an affinity reagent.
      Initially, concentrated cell culture supernatants were screened for receptor
      binding activity using immobilized ECK-X in a surface plasmon resonance detection
      system. Subsequently, supernatants from selected cell lines were fractionated
      directly by receptor affinity chromatography, resulting in the single-step
      purification of B61, a protein previously identified as the product of an early
      response gene induced by tumour necrosis factor-alpha. We report here that
      recombinant B61 induces autophosphorylation of ECK in intact cells, consistent
      with B61 being an authentic ligand for ECK. ECK is a member of a large orphan
      receptor protein-tyrosine kinase family headed by EPH, and we suggest that
      ligands for other members of this family will be related to B61, and can be
      isolated in the same way.

PMID- 8139692
TI  - DNA-like double helix formed by peptide nucleic acid.
AB  - Although the importance of the nucleobases in the DNA double helix is well
      understood, the evolutionary significance of the deoxyribose phosphate backbone
      and the contribution of this chemical entity to the overall helical structure and
      stability of the double helix is not so clear. Peptide nucleic acid (PNA) is a
      DNA analogue with a backbone consisting of N-(2-aminoethyl)glycine units (Fig. 1)
      which has been shown to mimic DNA in forming Watson-Crick complementary duplexes
      with normal DNA. Using circular dichroism spectroscopy we show here that two
      complementary PNA strands can hybridize to one another to form a helical duplex.
      There is a seeding of preferred chirality which is induced by the presence of an
      L- (or D-) lysine residue attached at the carboxy terminus of the PNA strand.
      These results indicate that a (deoxy)ribose phosphate backbone is not an
      essential requirement for the formation of double helical DNA-like structures in
      solution.

PMID- 8139693
TI  - Expression cloning of a mammalian proton-coupled oligopeptide transporter.
AB  - In mammals, active transport of organic solutes across plasma membranes was
      thought to be primarily driven by the Na+ gradient. Here we report the cloning
      and functional characterization of a H(+)-coupled transporter of oligopeptides
      and peptide-derived antibiotics from rabbit small intestine. This new protein,
      named PepT1, displays an unusually broad substrate specificity. PepT1-mediated
      uptake is electrogenic, independent of extracellular Na+, K+ and Cl-, and of
      membrane potential. PepT1 messenger RNA was found in intestine, kidney and liver
      and in small amounts in brain. In the intestine, the PepT1 pathway constitutes a
      major mechanism for absorption of the products of protein digestion. To our
      knowledge, the PepT1 primary structure is the first reported for a proton-coupled
      organic solute transporter in vertebrates and represents an interesting
      evolutionary link between prokaryotic H(+)-coupled and vertebrate Na(+)-coupled
      transporters of organic solutes.

PMID- 8139694
TI  - Enzymatic activities correlate with chimaeric substitutions at the actin-binding
      face of myosin.
AB  - Myosins are a functionally divergent group of mechanochemical enzymes involved in
      various motile activities in cells. Despite a high degree of conservation in the
      amino-acid sequence of the 130K motor domain (head region) of the molecule, there
      are large differences in the enzymatic and motile activities (Tables 1 and 2) of
      myosins from diverse species and cell types. However, the degree of conservation
      is not uniform throughout the head sequence; therefore, one reasonable hypothesis
      is that the functional differences between myosins derive from the poorly
      conserved areas. The most prominent divergent region occurs at the 50K/20K
      junction, a region of the molecule sensitive to proteolytic digestion and a
      binding site for actin. We have now constructed chimaeras of this region of
      myosin by substituting the 9-amino-acid Dictyostelium junction region with those
      from myosins from other species and find that the actin-activated ATPase
      correlates well with the activity of the myosin from which the junction region
      was derived. Our results suggest that this region, likely to be part of the
      myosin head that interacts directly with actin, is important in determining the
      enzymatic activity of myosin.

PMID- 8139695
TI  - Shape-shifting serpins.
AB  - Recent structures of members of the serine proteinase inhibitor families
      (serpins) continue to emphasize the flexibility of the reactive loop and suggest
      possible 'active' conformations.

PMID- 8139696
TI  - Characterization of the prejunctional muscarinic receptors mediating inhibition
      of evoked release of endogenous noradrenaline in rabbit isolated vas deferens.
AB  - The aim of the present study was to characterize the prejunctional modulation of
      evoked release of endogenous noradrenaline in rabbit vas deferens by the use of
      muscarinic receptor agonists and subtype-preferring antagonists. Vasa deferentia
      of the rabbit were stimulated electrically by trains of 120 pulses delivered at 4
      Hz or trains of 30 pulses at 1 Hz. The inhibition by muscarinic agonists of the
      stimulation-evoked overflow of endogenous noradrenaline in the absence and
      presence of antagonists was used to determine affinity constants for antagonists.
      These values were compared with those observed at putative M1 receptors
      inhibiting neurogenic twitch contractions in the rabbit vas deferens and with
      affinity data obtained at M1(m1)-M4(m5) receptors in functional studies and
      binding experiments. The evoked overflow of noradrenaline from sympathetic nerves
      was enhanced by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine
      (DPCPX), the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'
      disulfonic acid (PPADS) and indomethacin, indicating a tonic inhibition by
      endogenous A1 and P2 purinoceptor agonists and prostanoids, respectively. The
      stimulation-evoked overflow at 4 Hz was not sensitive to inhibition by the
      muscarinic agonists methacholine or 4-(4-chlorophenylcarbamoyloxy)-2
      butynyltrimethylammonium iodide (4-Cl-McN-A-343). In contrast, at a stimulation
      frequency of 1 Hz the evoked noradrenaline release was decreased by muscarinic
      agonists (EC50): arecaidine propargyl ester (0.062 microM), 4-Cl-McN-A-343 (0.32
      microM), 4-(4-fluorophenylcarbamoyloxy)-2-butynyl-N-methyl-pyrrolidinium tosylate
      (4-F-PyMcN+; 0.48 microM) and methacholine (0.86 microM). The affinity constants
      of most of the muscarinic antagonists [atropine: pKB = 9.47; (R)-trihexyphenidyl:
      pKB = 9.18; pirenzepine: pA2 = 7.68; methoctramine: pKB = 6.90] are consistent
      with estimates of these antagonists at M1(m1) receptors determined in various
      functional and binding studies. The high antagonistic potency of pirenzepine and
      (R)-trihexyphenidyl and the agonistic activity of 4-F-PyMcN+ argue for the
      involvement of M1, and against that of M2 and M3 receptors in the inhibition of
      evoked noradrenaline overflow. However, the high apparent pKB of 8.30 for
      himbacine is not in accordance with an M1 receptor; by contrast, it would be
      compatible with the presence of M2 or M4 receptors. The potencies of the tested
      muscarinic agonists and antagonists largely agree with those obtained for the
      inhibition of neurogenic twitch responses (0.05 Hz) in the rabbit vas
      deferens.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8139697
TI  - Contractile effects of thrombin in porcine pulmonary arteries and the influence
      of thrombin inhibitors.
AB  - Thrombin catalyzes not only the conversion of fibrinogen to fibrin but also
      activates several receptor-mediated cell responses. In ring segments of porcine
      pulmonary arteries the contractile effect of thrombin was studied in the presence
      and absence of endothelium. The integrity of endothelium was assessed by the
      bradykinin-induced relaxation of PGF2 alpha (3 mumol/l)-precontracted vessels
      which was absent after mechanical removal of endothelium. Thrombin at 0.1 to 10
      U/ml (i.e. about 1-100 nmol/l) caused a sustained contraction in endothelium
      denuded arteries with a maximum at 20-30 min. In vessels with intact endothelium
      a significant increase in tension up to 1 U/ml was observed preceded by a
      transient relaxant response. The contractile effect in vessels with intact
      endothelium was comparatively weaker. This is probably due to the release of EDRF
      from endothelial cells since blockade of EDRF synthesis by NG-nitro-L-arginine
      augmented the thrombin-induced contractions in arteries with intact endothelium.
      Indomethacin did not alter the contractile effect. However, in vessels with
      endothelium and in endothelium-denuded vessels the contractions were reduced when
      extracellular calcium was omitted. Verapamil (10 mumol/l) significantly
      diminished the contractile effect only in endothelium-denuded vessels. On
      preincubation of endothelium-denuded arterial ring segments with myo-[2
      3H]inositol the addition of thrombin (10 U/ml) caused an accumulation of
      [3H]inositol-1,4,5-triphosphate (IP3). A maximum was observed after 2 min
      preceding the maximum increase in contraction. Measurement of thrombin-induced
      endogenous IP3 generation by radioreceptor assay yielded the same results. The
      thrombin-induced contractile effect requires the proteolytic activity of the
      enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139698
TI  - Modulation by cortisol of luteinizing hormone secretion from cultured porcine
      anterior pituitary cells: effects on secretion induced by phospholipase C,
      phorbol ester and cAMP.
AB  - Cultures of enzymatically dispersed porcine anterior pituitary cells were used to
      examine the effects of cortisol on luteinizing hormone secretion induced by a
      variety of compounds which activate different intracellular signal transduction
      mechanisms. Cells were pre-incubated with or without cortisol (200 micrograms/ml)
      for 3 days, washed and then incubated for 4 h with or without cortisol in the
      presence or absence of these compounds. Luteinizing hormone in the media was
      assayed by radioimmunoassay. Cortisol treatment had no effect on basal
      luteinizing hormone release, but reduced gonadotropin-releasing hormone (8.5 x
      10(-8) mol/l) stimulated luteinizing hormone secretion. Phospholipase C, 8-bromo
      cyclic adenosine 3',5'-monophosphate, and 12-O-tetradecanoyl-phorbol-13-acetate
      (an activator of protein kinase C) all stimulated luteinizing hormone secretion
      in a dose-dependent manner in cortisol-untreated cells. Pretreatment with
      cortisol inhibited luteinizing hormone secretion induced by phospholipase C and 8
      bromo-cyclic adenosine 3',5'-monophosphate, but did not affect the secretion of
      luteinizing hormone in response to 12-O-tetradecanoyl-phorbol-13 acetate.
      Cortisol inhibited GnRH-induced inositol phosphate production. Our results
      suggest that the inhibitory action of cortisol on stimulus-coupled luteinizing
      hormone secretion may be exerted at two different intracellular sites: (1) by
      inhibition of phospholipase C activity and (2) at a point distal to cyclic
      adenosine 3',5'-monophosphate generation.

PMID- 8139699
TI  - Characterization of a serotonin receptor endogenous to frog melanophores.
AB  - The response of a cell line of Xenopus laevis melanophores to serotonin was
      examined. Serotonin increased intracellular levels of cAMP and induced pigment
      dispersion in the cells. The responses depended on both the concentration of
      serotonin applied and on the time for which the cells were exposed to serotonin.
      Using a recently described, microtiter-plate-based bioassay, a series of
      serotonin receptor ligands were evaluated as agonists or antagonists at the
      melanophore serotonin receptor. The pharmacological profile suggests the presence
      of a receptor which shares some properties with but appears different from other
      previously described serotonin receptors.

PMID- 8139700
TI  - A hypotensive and bradycardic action of gamma 2-melanocyte-stimulating hormone
      (gamma 2-MSH) microinjected into the nucleus tractus solitarii of the rat.
AB  - In conscious and urethane-anesthetized rats intravenously (i.v.) administered
      gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), a melanotropin derived from
      the precursor peptide pro-opiomelanocortin (POMC), has been shown to induce a
      pressor response combined with a tachycardia. A site of action within the
      hindbrain, e.g. the nucleus tractus solitarii (NTS) or the area postrema (AP),
      has been suggested. In order to test the postulate that gamma 2-MSH acts within
      these hindbrain regions, the peptide was microinjected into various parts of the
      NTS and into the AP of urethane-anesthetized rats and blood pressure (BP) and
      heart rate (HR) were measured. Injection of gamma 2-MSH (100-500 pmol) into the
      NTS resulted in a dose-dependent decrease in BP and HR rather than in the
      expected pressor and tachycardiac response which is generally found in conscious
      and urethane-anesthetized rats following i.v. administration of the peptide. With
      respect to the depressor and bradycardiac effect the melanotropin was far more
      potent when injected into the pars commissuralis than into the medial part of the
      NTS. The responses were maximal after 3-4 min and lasted for about 15 min. gamma
      2-MSH had no effect when injected into the AP. It is noteworthy that also a
      hypotensive and bradycardic effect for gamma 2-MSH is found in pentobarbital
      anesthetized rats following i.v. administration. Therefore, we conclude that in
      addition to a pressor and tachycardic response gamma 2-MSH can elicit an opposite
      effect by interaction with structures within a discrete region in the NTS, the
      pars commissuralis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139701
TI  - Turning behavior induced by intrastriatal injection of neurotensin in mice:
      sensitivity to non-peptide neurotensin antagonists.
AB  - The intrastriatal injection of neurotensin (10 pg/mouse) elicited vigorous
      contralateral rotations which were not affected by disruption of dopaminergic
      transmission using 6-OHDA lesion of the striatum or systemic administration of
      spiroperidol (0.03 mg/kg). SR 48692, a selective non-peptide antagonist of
      neurotensin receptor, produced the following pattern of changes: a significant
      antagonism of rotations was observed at 0.04 and 0.08 mg/kg i.p. followed by a
      reinstatement of rotations at 0.16-0.64 mg/kg (at higher doses, a second
      antagonism occurred that lacked stereoselectivity). The reinstatement of
      rotations observed at 0.16 and 0.32 mg/kg of SR 48692 was abolished by
      spiroperidol and 6-OHDA lesions, suggesting the role of dopamine regulatory
      mechanisms.

PMID- 8139702
TI  - Pore formation by tetanus toxin, its chain and fragments in neuronal membranes
      and evaluation of the underlying motifs in the structure of the toxin molecule.
AB  - The pore-forming activity of tetanus toxin, its chains and fragments was studied
      on membrane patches from spinal cord neurons of fetal mice using the outside-out
      patch-clamp configuration. 1. The dichain tetanus toxin forms pores at pH 5, but
      not at pH 7.4. The elementary pore conductance is 38.4 +/- 1.1 pS and
      nonselective for small cations. The open probability of the pores is voltage
      dependent and increases with membrane depolarisation. The pores activate at +80
      mV with a time constant of about 20 ms and deactivate at -80 mV with two time
      constants of about 2 ms and 10 ms. Besides the elementary pore conductance,
      larger pore conductances which are multiples of the elementary conductance were
      observed. With increasing conductances, their frequency of occurrence decreases
      exponentially. 2. The light chain of tetanus toxin alone does not form pores in
      neuronal membranes at pH 5 or at pH 7.4. 3. The heavy chain of tetanus toxin
      forms pores at pH 5 as well as at pH 7.4. The single pore conductance increases
      from 35.0 +/- 1.2 pS at pH 5 to 43.2 +/- 1.8 pS at pH 7.4. The pores allow mono-
      and divalent cations and chloride ions to pass. Only at pH 5 do they have a
      voltage dependence with time constants identical to those obtained with tetanus
      toxin. 4. Secondary structure predictions show a high density of presumably
      helically organized elements in fragment beta 2 (45 kDa) of the heavy chain
      between residues 700-850.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139703
TI  - P2-purinoceptor antagonists discriminate three contraction-mediating receptors
      for ATP in rat vas deferens.
AB  - The sites of action at which ATP elicits contraction of the rat vas deferens were
      studied by means of the P2-purinoceptor antagonists pyridoxalphosphate-6
      azophenyl-2',4'-disulfonic acid (iso-PPADS), suramin and reactive blue 2.
      Increasing concentrations of iso-PPADS (up to 1 mM), suramin (up to 1 mM) and
      reactive blue 2 (up to 320 microM) reduced and eventually abolished contractions
      elicited by the P2x-purinoceptor-selective agonist alpha,beta-methylene ATP 3
      microM with IC50 values of 2.1, 10.1 and 27.0 microM, respectively. In contrast,
      iso-PPADS and suramin caused only a partial inhibition of contractions elicited
      by ATP 1 mM, maximal reduction by about 40%, IC50 values 1.3 and 5.0 microM,
      respectively; reactive blue 2 did not change ATP-induced contractions. In tissues
      exposed to iso-PPADS 320 microM throughout, increasing concentrations of reactive
      blue 2 or suramin decreased contractions elicited by ATP 1 mM, IC50 values 2.6
      and 14.5 microM, respectively. In tissues exposed to suramin 320 microM
      throughout, increasing concentrations of iso-PPADS decreased contractions
      elicited by ATP 1 mM, IC50 37.9 microM, whereas reactive blue 2 slightly enhanced
      these contractions. In tissues exposed to reactive blue 2 100 microM throughout,
      increasing concentrations of iso-PPADS reduced contractions elicited by ATP 1 mM,
      IC50 26.6 microM, whereas suramin caused no change. Pre-exposure to alpha,beta
      methylene ATP 1 microM to desensitize P2x-purinoceptors reduced the response to
      ATP 1 mM by 91% in otherwise untreated tissues, but did not reduce the response
      to ATP 1 mM in tissues exposed throughout to iso-PPADS 320 microM, suramin 320
      microM or reactive blue 2 100 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139704
TI  - Adenosine receptor-mediated inhibition of cardiac adenylyl cyclase activity may
      involve multiple receptor subtypes.
AB  - We previously reported that the adenosine receptor agonist N6
      phenylisopropyladenosine (R-PIA) inhibits adenylyl cyclase in detergent
      permeabilized embryonic chick ventricular myocytes in the presence of the
      adrenergic receptor agonist, isoproterenol (Ma and Green 1992). The slope of the
      dose response curve of this inhibition is very shallow (nH 0.3-0.4). The present
      studies on detergent-permeabilized chick myocytes evaluate the mechanisms
      underlying this shallow inhibition curve. We find that in contrast to R-PIA, two
      additional adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and 2
      chloro-N6-cyclopentyladenosine (CCPA), inhibit cardiac adenylyl cyclase activity
      in a monophasic, dose-dependent manner (nH approximately 1). Two A1 adenosine
      receptor antagonists, 8-cyclopentyl-1,3,-dipropylxanthine (CPX) and 3-(4
      amino)phenethyl-1-propyl-8-cyclopentylxanthine (BW-A884U) affect the R-PIA
      responses differently. BW-A884U shifts the R-PIA dose response curve to the right
      in a parallel fashion while CPX both shifts the R-PIA response curve and
      increases its steepness. Cardiac A1 adenosine receptors were further
      characterized using one antagonist ([3H]CPX) and two agonist ([3H]R-PIA and
      [3H]CCPA) radioligands. [3H]CPX binds to the adenosine receptors in detergent
      permeabilized ventricular myocytes with a Kd value of 3.3 +/- 0.2 nM and a BMAX
      value of 30.1 +/- 2.4 fmol/mg protein (means +/- SEM; N = 4). [3H]R-PIA detects
      more sites than [3H]CCPA (22.8 +/- 4.0 and 8.3 +/- 1.3 fmol/mg protein,
      respectively; GTP-free conditions). CPA and CCPA inhibit [3H]R-PIA binding in a
      shallow, dose-dependent manner (nH approximately 0.4), while R-PIA and CPA
      inhibit [3H]CCPA binding with a nH approximately 1.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8139706
TI  - [Somnambulism in adults].

PMID- 8139705
TI  - Different mechanisms of the inhibition of the transient outward current in rat
      ventricular myocytes.
AB  - The mechanism of drug-induced inhibition of the transient outward current, Ito,
      has been investigated in rat ventricular myocytes using the whole cell patch
      clamp technique. Ito was activated by 300 ms depolarizing voltage clamp steps in
      10 mV increments from -50 mV up to +40 mV. At +40 mV, Ito peaked after about 3
      ms, and the time course of inactivation was appropriately described by two time
      constants, tau fast = 17 ms and tau slow = 203 ms. Verapamil, quinidine sulfate
      and nifedipine preferentially depressed Ito at the end of the 300 ms depolarizing
      voltage clamp step; the inactivation of Ito was accelerated by all drugs, whereas
      peak Ito was less affected. The time course of drug action at +40 mV was
      calculated by the fractional changes of Ito. Verapamil, quinidine sulfate and
      nifedipine exerted a block of Ito increasing during the depolarizing voltage
      clamp step. The onset of block in response to verapamil, quinidine sulfate and
      nifedipine (30 mumol/each) was appropriately described by monoexponential
      functions with time constants tau on = 9.3, 1.7 and 1.1 ms, respectively. Relief
      from block by verapamil, quinidine sulfate and nifedipine at -50 mV was assessed
      by comparison of the recovery process of peak Ito from inactivation with or
      without drugs. tau off amounted to 695 ms in the case of quinidine sulfate;
      verapamil and nifedipine did not significantly affect the recovery process so
      that the determination of the time course of relief from block was not
      possible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8139707
TI  - [A causal connection between lung cancer and passive smoking: the report from the
      American Environmental Protection Agency].

PMID- 8139708
TI  - [Risk of lung cancer due to passive smoking still unproven].

PMID- 8139709
TI  - [Health risk due to passive smoking: opposite results or opposite opinions].

PMID- 8139710
TI  - [Survival of patients following the diagnosis of AIDS in the Amsterdam region,
      1982-1991].
AB  - OBJECTIVE: To evaluate the survival of 975 AIDS patients diagnosed in the
      Amsterdam region between 1982 and 1991, with follow-up until December 31st, 1992.
      METHODS: Analysis of data from the active AIDS surveillance system for the
      Amsterdam region at the Municipal Health Service. RESULTS: Amsterdam region
      residents had 1, 2 and 3-year survivals of 69.8%, 42.6% and 21.2%, respectively.
      The 5-year survival was 7.7%. The median survival probability for all patients
      showed great improvement, from 9 months in 1982-1985 to 26 months in 1990. For
      patients initially presenting with only Pneumocystis carinii pneumonia (PCP) the
      greatest improvement occurred between the period 1982-1985 and the year 1986. For
      patients without PCP the most important improvement occurred one year later. From
      1988 onwards no important improvement in the 1-year survival is noticed. The 2
      year survival, however, appears still to be increasing. In a Cox proportional
      hazards model the following variables were found to be independent predictors for
      survival: age at diagnosis, earliest clinical AIDS manifestations, year of
      diagnosis and HIV risk group. No differences were seen in the 1 and 2-year
      survival probabilities for men and women with AIDS. Heterosexual men and women
      tended to have a poorer survival than intravenous drug users and homosexual and
      bisexual men. CONCLUSION: A noticeable improvement in the survival probability
      with time occurred for AIDS patients living in the Amsterdam region through the
      years 1982-1991, although the overall survival after AIDS diagnosis is still
      poor. The 1-year survival appears to have reached a plateau, the 2-year survival
      is still increasing. Improved clinical experience, awareness of HIV related
      complaints in high risk groups, better diagnostic methods and the availability of
      proper medication (prophylactic and treatment) are the most likely explanations
      of the improvement in survival.

PMID- 8139711
TI  - [Birth weight percentiles of premature infants needs to be updated].
AB  - OBJECTIVE: To analyse whether the conventional so-called Kloosterman charts for
      birthweight of preterm infants based on data from 1931-1965 are still valid.
      DESIGN: Descriptive investigation. LOCATION: The Netherlands. METHOD: Data were
      obtained from the 'project of the premature and small for gestational age' (POPS)
      survey in 1983. The population consisted of 855 Caucasian infants born after a
      pregnancy of 24-31 weeks. RESULTS: In nearly all gestational age categories the
      percentages of small-for-gestational age infants were higher than the 10% they
      should have been by definition; the percentages of large-for-gestational age
      infants were much lower than 10%. After exclusion of elective births the
      percentages remained different. CONCLUSION: These shifts in the birthweight
      distribution are probably the result of changes in obstetrics. The birthweight
      percentiles for preterm births will have to be updated.

PMID- 8139712
TI  - [Endo-urological drainage in urinary outflow obstruction caused by cancer].
AB  - OBJECTIVE: To determine indications and results of endourological upper urinary
      tract drainage in patients with obstruction due to malignancy. DESIGN:
      Retrospective. SETTING: University Hospital Groningen. METHOD: In the period 1987
      1992, 57 patients with upper urinary tract obstruction due to cancer were treated
      primarily with a double-J stent (n = 21) or a percutaneous nephrostomy (n = 36,
      later replaced by a double-J stent in 13). RESULTS: Indications were: severe
      renal failure following bilateral ureteral obstruction due to malignancy (n =
      17), or unknown cause (n = 19), to optimise a compromised kidney function before
      chemotherapy (n = 7), to resolve pain caused by unilateral obstruction (n = 10),
      or other (n = 4). The tumours originated most often in the cervix uteri, followed
      by the urinary bladder, the prostate and the corpus uteri. Minor complications
      occurred in 34 of the 57 patients (60%): transient haematuria (22 x), urgency
      caused by the distal tip of the double-J catheter (8 x), dislocation (17 x) or
      obstruction (6 x) of the nephrostomy catheter. Major complications were observed
      in 5 patients with a double-J stent: sepsis (1 x), catheter break (1 x), ureteral
      perforation (2 x) and fistulization between the ureter and iliac artery (1 x).
      Survival after drainage varied from several days to 8 years (mean 23 months). In
      5 patients treated with drainage only to prolong survival, survival was 0.5-16
      months (mean 7.3). CONCLUSION: Endourological drainage may be applied to patients
      with localised disease, in whom further therapy holds the promise of prolonged
      survival. However, in view of the low complication rate, selected patients who
      are on a palliative course and still have rapidly progressive disease can also
      benefit from extended life-time after endourological drainage.

PMID- 8139713
TI  - [Skin lesions as a rare initial symptom of Kahler's disease].
AB  - Multiple skin lesions developed in a 70 year-old-man. Pathological examination
      revealed plasmacytomas. Because of the presence of a IgD paraprotein and 15%
      abnormal plasma cells in the bone marrow Kahler's disease of the IgD type was
      diagnosed. In accordance with literature the course of the disease was rapidly
      progressive. After an initial favourable response to chemotherapy and
      radiotherapy, the patient died one year after diagnosis. Extraosseous tissue
      involvement and hepatosplenomegaly are well-known phenomenon of IgD-Kahler's
      disease. Skin plasmacytomas as the first symptom of the disease are very rare.

PMID- 8139714
TI  - [Tendinitis of the Achilles tendon caused by pefloxacin and other fluoroquinolone
      derivatives].
AB  - Four cases were reported to the Netherlands Pharmacovigilance Foundation LAREB of
      Achilles tendinitis, as a suspected adverse reaction to pefloxacin; the patients
      were two men of 64 years old, one of 33 and one of 76 years old. More than twenty
      cases of tendinitis have previously been described in the literature in
      association with pefloxacin and various other fluoroquinolone derivatives; tendon
      rupture was a frequent complication. In the data base of the WHO Collaborating
      Centre for International Drug Monitoring tendon disorders are a very rare
      reaction, with the exception of fluoroquinolone derivatives. More information is
      needed with regard to the frequency of tendinopathy during the use of pefloxacin
      and the other drugs in this group. Achilles tendon rupture is an serious
      condition, often requiring surgical treatment. Patients using a fluoroquinolone
      derivative should be informed of the risk of developing tendinitis and tendon
      rupture.

PMID- 8139715
TI  - [Traumatic carotid artery stenosis with cerebral infarct].

PMID- 8139716
TI  - [Bronchiectasis; clinical aspects, diagnosis and treatment].

PMID- 8139717
TI  - [Family practice and nursing home medicine; a comparison].

PMID- 8139718
TI  - [Deficient health care for diabetic patients with foot problems].

PMID- 8139719
TI  - [Proton spin resonance tomography of the foot in patients with diabetes
      mellitus].

PMID- 8139720
TI  - [Antibiotic therapy in diabetic foot ulcers].

PMID- 8139721
TI  - [Molecular-genetic leads for prevention and treatment of colorectal carcinoma].

PMID- 8139722
TI  - [A specialized outpatient foot clinic for diabetic patients decreases the number
      of amputations and is cost saving].
AB  - OBJECTIVE: Evaluation of the effectiveness of a foot clinic for diabetes
      patients. DESIGN: Retrospective study and cost-effect analysis. SETTING: Spaarne
      Hospital, Heemstede. METHOD: The effectiveness of 5 years's activity (1987-1991)
      of a foot clinic was measured by comparing its patient population, the presenting
      ulcers and amputations, the average stay in hospital and the cost reduction with
      1983-1986. RESULTS: From 1987 to 1991 4323 diabetic check-ups were done in the
      clinic, of which 810 were first referrals. Of these first referrals 112 presented
      with a leg ulcer. Compared with the period before the establishment of the clinic
      in 1987, hospital admission for diabetic foot problems decreased from 48 to 29
      days and 30 admissions could be prevented. The number of amputations decreased by
      43%. The reduction in costs was calculated to be about Dfl. 325,000.--annually.
      CONCLUSION: A specialised foot clinic reduces morbidity and cost in diabetes foot
      care. Central figures in this clinic are a chiropodist and a nurse, supported by
      a surgeon and specialists in internal diseases, rehabilitation and footwear.

PMID- 8139723
TI  - [Large variation in the treatment of foot infections in diabetic patients in The
      Netherlands].
AB  - OBJECTIVE: To determine the treatment of foot infections in patients with
      diabetes mellitus and the implementation of the Dutch consensus guidelines.
      DESIGN: Questionnaire. SETTING: Nationwide. METHOD: To 180 internists and
      paediatricians were sent a letter explaining the objective of the survey and a
      questionnaire. After two months an identical questionnaire was sent, with the
      request to return it when the first questionnaire had not been returned yet.
      RESULTS: Seventy-three questionnaires (40%) were returned of which 63 were
      evaluable. The main reason for hospitalisation was the threat of limb loss (90%).
      Most patients presenting with superficial wound infections were treated with
      local surgical procedures (90%); however, 16% of the responders considered
      hospitalisation indicated. If osteomyelitis was present 81% of the responders
      would hospitalize the patient. Antibiotic treatment was instituted by 93%. In
      all, 11 different antibiotics were used. Of antibiotic combinations the
      combination of penicillin and lincomycin was used most frequently and the
      recommended combination of aminoglycoside and lincomycin least. The main reason
      for using a combination of antibiotics was presence of polymicrobial flora (93%).
      CONCLUSION: We conclude that treatment of diabetic foot is still very diverse in
      spite of the consensus guidelines.

PMID- 8139724
TI  - [Surgical removal of the lip vermilion in the treatment of lip carcinoma;
      experience in 8 patients].
AB  - OBJECTIVE: To present the results of lipshave surgery in patients treated for
      squamous cell carcinoma of the lip, with actinic changes. DESIGN: Descriptive.
      SETTING: Medical Centre, Leeuwarden, the Netherlands. METHOD: The histories were
      studied of 8 patients with carcinoma of the lip treated in 1988-1992 with
      lipshave surgery, if necessary in combination with a wedge excision.
      Postoperative results and lip function were observed; follow-up was from 9 to 53
      months. RESULTS: Two patients died prematurely from another cause than the lip
      cancer. In the other patients there were no signs of recurrence of the carcinoma.
      Although all patients had decreased lip sensibility, lip functions were fairly
      intact: 2 patients complained of drooling at times or rarely, 1 drooled often and
      3 never. For 1 patient speaking had become a little more difficult, in the other
      5 cases it had not changed. The drinking test was performed properly in all
      cases. CONCLUSION: Lipshave surgery is a reliable treatment for lip carcinoma
      with actinic changes and also preserves the lip functions.

PMID- 8139725
TI  - [An abscess as an unexpected complication following epidural anesthesia].
AB  - A 58-year-old man underwent surgery for an inguinal hernia. Surgery was performed
      under epidural anaesthesia. The patient afterwards developed increasing low back
      pain. Magnetic resonance imaging showed an epidural abscess, which was drained by
      laminectomy. The patient recovered without neurological sequelae.

PMID- 8139726
TI  - [Familial ovarian carcinoma].

PMID- 8139727
TI  - [Postinfectious tropical malabsorption and the differences with non-tropical
      sprue (celiac disease)].

PMID- 8139728
TI  - [An unusual cause of hypertension in pregnancy with fatal outcome].

PMID- 8139729
TI  - Cardiovascular mortality of patients with polycystic kidney disease on dialysis:
      is there a lesson to learn?

PMID- 8139730
TI  - Advances in pharmacology and therapy of nephritides.

PMID- 8139731
TI  - Loss of anionic sites on the glomerular basement membrane in transplant
      glomerulopathy.
AB  - We studied anionic sites on the glomerular basement membrane in patients with
      chronic renal transplant rejection having clinical and histological features of
      transplant glomerulopathy. All patients had significant proteinuria (greater than
      1 g/24 h as well as light- and electron-microscopic features very like focal
      segmental glomerulosclerosis, though no patient had that disease in the native
      kidney. A significant reduction in the density and absolute number of anionic
      sites was observed compared with controls and with patients having stable graft
      function. The findings suggest that the loss of anionic sites may play an
      important part in the pathogenesis of transplant glomerulopathy.

PMID- 8139732
TI  - Creatol, a creatinine metabolite, as a useful determinant of renal function.
AB  - Analysis of creatol (CTL, 5-hydroxycreatinine), an oxidative creatinine (Cr)
      metabolite, in serum and urine of human subjects has indicated that CTL is a
      useful determinant of renal function. The existence itself of serum CTL (s-CTL)
      could be a diagnostic sign for chronic renal failure (CRF): in all normal
      subjects, s-CTL was undetectable, but s-CTL was detectable in sera of all
      patients with CRF (s-Cr: > 2.0 mg/dl). And the s-CTL values increased in
      proportion to the severity of CRF in such patients. Furthermore, the molar ratio
      (CTL/Cr) in both urine and serum increased significantly in proportion to the
      severity of CRF. Our results indicated not only hyperproduction of CTL but also
      higher oxygen stress in patients according to the progression of CRF. The
      diagnostic importance of the CTL value and the CTL/Cr ratio are discussed.

PMID- 8139733
TI  - Effect of recombinant human erythropoietin treatment in uremic patients on oxygen
      affinity of hemoglobin.
AB  - Anemia of chronic renal failure is associated with a reduced affinity of
      hemoglobin for oxygen (Hb-O2 affinity). It has been reported that the correction
      of renal anemia by recombinant human erythropoietin (rhuEPO) treatment could be
      associated paradoxically with a further decrease in Hb-O2 affinity. We
      investigated changes in the compensatory mechanisms of chronic renal anemia
      during 25 weeks of rhuEPO treatment, in 19 chronic hemodialyzed (HD) patients.
      There was no significant variation of mean standard P50 (P50std). Average 2,3
      diphosphoglycerate (DPG) increased after 13 weeks and remained stable. The large
      interindividual variations prompted us to study delta P50std and delta Hb. We
      demonstrated a negative correlation between delta P50std and delta Hb. Thus,
      P50std increased in patients who did not immediately correct their anemia and
      decreased in patients whose Hb values rose. These data showed that the major
      factor influencing variations of Hb-O2 affinity in chronic HD patients treated by
      rhuEPO is the variation of Hb concentrations. In our study, it was demonstrated
      that the most important rise in P50std and 2,3-DPG occurred in patients who were
      late responders to rhuEPO.

PMID- 8139734
TI  - Serum coenzyme Q10 in uremic patients on chronic hemodialysis.
AB  - In a group of 48 chronic hemodialysis patients, serum levels of coenzyme Q10
      (CoQ) have been measured and appeared abnormally low in 62% of cases. Figures
      were positively correlated to those of serum vitamin E (vit E), although the
      latter were within a normal range. The chronic hemodialysis (CHD) patients with
      normal serum values of CoQ exhibited higher blood triglycerides. Pathologically
      low levels of serum vit E were found only in uremic subjects on conservative
      regimen with dietary restrictions and low compliance to protein-caloric intake.
      The reduced CoQ levels may contribute to the defective serum antioxidant activity
      and the increased peroxidative damage in uremic patients on CHD.

PMID- 8139735
TI  - Pharmacokinetics of carboplatin in a patient suffering from advanced ovarian
      carcinoma with hemodialysis-dependent renal insufficiency.
AB  - Pharmacokinetics of carboplatin were determined in a patient suffering from
      advanced ovarian cancer with total hemodialysis-dependent chronic renal failure
      undergoing 3 consecutive cycles of chemotherapy. Dosage was adjusted to reach
      active AUC (area under the plasma concentration versus time curve) of
      ultrafilterable carboplatin. A hemodialysis, performed 24 h after administration
      results in a decrease of 20% of ultrafilterable carboplatin AUC. The relative
      dialysis efficacy of ultrafilterable carboplatin was great: 84 +/- 3%. The
      chemotherapy regimen consisted of carboplatin-cyclophosphamide combination for 6
      cycles every 4 weeks. After treatment completion, the patient showed a complete
      response and remains disease free 16 months after the end of the treatment.
      Carboplatin-based chemotherapy can be given to patients undergoing chronic
      hemodialysis without life-threatening toxicity with a dialysis performed 24 h
      after the administration and with a dose adjustment of carboplatin to reach a AUC
      of 6 mg/ml.min for untreated patients. In these conditions, response in platinum
      sensitive tumors can be obtained.

PMID- 8139736
TI  - Quantitation of glutathione transferase-pi in the urine by radioimmunoassay.
AB  - A radioimmunoassay procedure for the quantitation of glutathione transferase-pi
      was developed in order to determine the levels of this protein in human urine.
      The enzyme was isolated from human placenta with a purification factor of 366
      (compared to the original high-speed supernatant fraction), and upon gel
      electrophoresis, only a single band was seen. Polyclonal antisera were
      subsequently raised in rabbits and found to be suitable for a radioimmunoassay.
      Glutathione transferase-pi was localized immunohistochemically to the cells of
      the distal tubules, the thin loop of Henle and the collecting ducts in the
      kidney. In contrast, the alpha-isoenzyme was localized exclusively in the
      proximal tubular epithelium. Samples of urine from healthy individuals contained
      about 6 ng of the pi-transferase/ml. The method proved to be specific for
      glutathione transferase-pi, and no cross-reaction with the alpha- or mu
      transferase or with other proteins occasionally appearing in urine occurred. The
      protein was quite stable upon storage and insensitive to variations in the urine
      pH. Thus, it appears that glutathione transferase-pi can be conveniently
      quantitated by radioimmunoassay and changes in the concentration of this protein
      in human urine thus monitored.

PMID- 8139737
TI  - Use of urinary parameters in the diagnosis of total acute renal artery occlusion.
AB  - Limited attention has been paid to the composition of the small amounts of urine
      that are frequently produced by patients with acute renal failure (ARF) of
      vascular origin. We have investigated the value of basic urinary parameters in
      the early diagnosis of total or partial acute renal artery occlusion (ARAO). We
      have reviewed the records of 30 patients with ARF: group 1 (n = 10) had total
      ARAO; group 2 (n = 10) had unilateral ARAO with a contralateral functioning
      kidney, and group 3 (n = 10) had hemodynamically mediated ARF subsequent to a
      major vascular abdominal surgical procedure, without arterial thrombosis. Serum
      sodium, potassium, urea, creatinine and osmolality, as well as urinary sodium,
      potassium, urea, creatinine and osmolality, were determined by standard
      techniques, and the fractional excretion of sodium (FENa) was calculated. Serum
      parameters were similar in all groups. Urinary sodium and FENa were higher in
      group 1 than in the other groups (p < 0.01), while urinary potassium was lower (p
      < 0.05). Urinary urea (p < 0.01) and osmolality (p < 0.05) were higher in group 2
      than in the other groups, revealing a prerenal pattern in some cases. Serum and
      urinary concentrations of sodium, urea and creatinine and osmolality were similar
      in group 1, while respective serum and urinary concentrations and osmolality were
      different from each other in the other groups. Analysis of urine provides a
      useful diagnostic tool in ARF of vascular origin. When urinary concentrations of
      sodium, urea and creatinine are similar to those in serum and FENa approaches
      100%, the strong likelihood of total ARAO should be acknowledged, and renal
      arteriography is mandatory.

PMID- 8139738
TI  - Uninephrectomy aggravates tubulointerstitial injury in rats with adriamycin
      nephrosis.
AB  - The effects of uninephrectomy on the function and structure of the remnant kidney
      were assessed in rats with Adriamycin-induced nephrosis, 12 weeks after the
      injection of Adriamycin. The kidney volume of Adriamycin-treated
      uninephrectomized rats (NX-AD) was 2.3 times that of sham-operated, Adriamycin
      treated animals (SH-AD; p < 0.001). The marked renal enlargement in NX-AD animals
      was due to the development of large tubular cysts. Following uninephrectomy, the
      fractional volume of tubular lumen almost doubled (NX-AD, 0.33 +/- 0.02; SH-AD,
      0.17 +/- 0.02; p < 0.001) and the absolute volume of tubular lumen increased more
      than fourfold (NX-AD, 0.51 +/- 0.08 ml; SH-AD, 0.12 +/- 0.02 ml; p < 0.001). The
      frequency of tubular lumen with a large cross-sectional area (> or = 40,000
      microns 2) was 5.8 +/- 1.1% in NX-AD and 0.7 +/- 0.2% in SH-AD groups (p <
      0.001). The fractional volume of interstitial fibrosis in NX-AD animals was
      larger than in SH-AD (0.09 +/- 0.02 versus 0.04 +/- 0.01%, p < 0.05). As opposed
      to the worsening of tubulointerstitial disease, single-kidney glomerular
      filtration rate, fractional protein clearance, glomerular volume and the extent
      of glomerular sclerosis did not differ significantly in NX-AD as compared to SH
      AD groups. This study shows that uninephrectomy in rats with Adriamycin nephrosis
      worsens interstitial nephrosis and aggravates the formation of tubular cysts,
      leading to a macrocystic kidney disease. These changes are not associated with an
      increase in glomerular sclerosis.

PMID- 8139739
TI  - Mesangial matrices act as mesangial channels to the juxtaglomerular zone. Tracer
      and high-resolution scanning electron-microscopic study.
AB  - The mesangium is centrally located in the glomerulus and plays an important role
      in the microcirculation within the glomerulus. In order to reveal the role of the
      mesangial matrix in the microcirculation, the movement of native anionic ferritin
      into the juxtaglomerular region was tracked following the intravenous injection
      of ferritin into rats. The three-dimensional ultrastructures of the mesangial
      matrix and juxtaglomerular apparatus were studied by conventional scanning and
      high-resolution scanning electron microscopy after removal of the cellular
      components. Many ferritin particles were observed from the glomerular capillary
      to the mesangial matrix, in the mesangial matrix of the juxtaglomerular apparatus
      and in the tubular lumen of the macula densa after the injection of ferritin.
      Secretion of macromolecules from the distal tubules seems to be one of the exits
      from the juxtaglomerular zone. The mesangial matrix was continuous from the
      vascular pole to the periphery like a branching tree. The intraglomerular
      mesangial matrix was continuous to the extraglomerular mesangial matrix in the
      juxtaglomerular region. The mesangial matrix appeared to consist of a polygonal
      meshwork structure of thin fibrils and pores with high-resolution scanning
      electron microscopy. The thinnest fiber was approximately 6-nm wide, and the pore
      size was averaged 20 nm in diameter. We were able to demonstrate the meshwork
      structure of the mesangial matrix, thus giving the morphological basis of the
      mesangial matrix to serve as mesangial pathway from the intraglomerular to the
      extraglomerular mesangial matrix.

PMID- 8139740
TI  - Meshwork structures in bovine glomerular and tubular basement membrane as
      revealed by ultra-high-resolution scanning electron microscopy.
AB  - We examined the ultrastructure of the bovine glomerular basement membrane (GBM)
      and tubular basement membrane (TBM) using ultra-high-resolution scanning electron
      microscopy after conductive staining without metal coating. Purified basement
      membranes (BMs) were obtained by sonication and acellular BMs by detergent
      treatments. Purified GBMs (PGBMs) and acellular GBMs (AGBMs) showed similar
      meshwork structures composed of regular round or oval pores and branching
      strands. Pore diameters were 10.2 +/- 2.4 nm (mean +/- SD) in PGBMs and 9.8 +/-
      3.1 nm in AGBMs. Purified TBMs (PTBMs) and acellular TBMs (ATBMs) exhibited
      heterogeneous meshwork structures in which compact meshes in the cristae were
      combined with coarse meshes in the invaginations on the epithelial surfaces. Pore
      diameters were 12.6 +/- 5.2 nm in PTBMs and 11.4 +/- 4.0 nm in ATBMs which were
      significantly larger than those in GBMs. The width of the strands ranged from 3
      to 15 nm in all BMs. A 4 M guanidine hydrochloride extraction of the acellular
      BMs revealed large polygonal networks in the invaginations of the TBM and twisted
      strands which were considered to be type IV collagen fibrils. Ultra-high
      resolution scanning electron microscopy and conductive staining were useful for
      the study of three-dimensional architectures of BMs and revealed heterogeneous
      meshwork structures in the GBM and TBM which were probably caused by a different
      ratio of the major components.

PMID- 8139741
TI  - Reconstruction of blood flow distribution in the rat kidney during postischemic
      renal failure.
AB  - Inner medullary blood flow has been found to remain nearly unchanged during
      postischemic renal failure, despite a severely disturbed perfusion in the outer
      medulla. In order to elucidate this discrepancy, rats were subjected to 1 h left
      renal artery occlusion and 1 h reflow. The blood plasma was then labeled by dye
      conjugated globulin for 1 min. The in vivo indicator distribution was
      histologically analyzed, especially in the medullary vascular bundles. The
      filling there was observed along a section plane positioned through the inner
      stripe along the long and the short axis of the organ. Vessels centrally located
      within the bundles were more labeled than those in the periphery of the bundles.
      In addition, the degree of filling on the whole was almost twice as high in the
      tissue near the renal sinus as in the central area. At the same time, filling
      defects in the renal papilla were restricted mostly to the center of that tissue.
      The observations support the assumption that differences in blood flow
      obstruction exist within each bundle. They also show that perfusion defects of
      the outer medulla occur more readily in the center of the organ, thus allowing
      blood to enter the inner medulla via vascular bundles located marginally,
      adjacent to the renal sinus of the kidney.

PMID- 8139742
TI  - Familial interstitial nephropathy without hyperuricemia.
AB  - Progressive hereditary nephropathy is described in 6 members of a single family.
      Renal biopsies, performed in 3 patients, revealed tubular atrophy, interstitial
      fibrosis, and lymphomonocytic infiltration associated with severe vascular
      lesions. These features were disproportionately serious when related to age,
      arterial pressure, and renal function. Similar familial nephropathy has been
      reported in the literature, generally in association with gout or asymptomatic
      hyperuricemia. The patients described here had normal blood concentrations of
      uric acid. It is proposed that the members of the present group of patients are
      suffering from the same interstitial nephropathy as that described in the
      literature and that the hyperuricemia found by other investigators is
      coincidental and does not play a pathogenetic role.

PMID- 8139743
TI  - Focal glomerular sclerosis and nephrotic syndrome in spondyloepiphyseal
      dysplasia.
AB  - The association of a spondyloepiphyseal dysplasia and disproportionate short
      stature with focal glomerular sclerosis is reported in two girls. Renal disease
      manifested by proteinuria at the age of 2.5 and 11 years, leading to treatment
      resistant nephrotic syndrome over 15 and 45 months, respectively. One patient
      went into end-stage renal failure shortly after nephrotic syndrome developed, the
      other died from sepsis. The association of spondyloepiphyseal dysplasia and focal
      glomerular sclerosis with nephrotic syndrome may represent a distinct disease
      entity.

PMID- 8139744
TI  - High prevalence of silent gallstone disease in dialysis patients.
AB  - Gallstone disease was detected in 28% of 119 patients on regular dialysis
      treatment. The disease was silent in 82% of the patients. Stones were radiolucent
      in 88% of the cases, radioopaque in 8% and mixed in 4%. Among 49 variables
      considered, increasing age was the only variable that correlated significantly
      with increasing prevalence of gallstone disease. Since no relationships were
      found between gallstones and age or modes of dialysis, it is conceivable that
      some mechanism(s) linked with the preexisting chronic nephropathy might have been
      involved in the development of cholelithiasis. End-stage renal disease could be
      another so far unrecognized risk factor for cholelithiasis.

PMID- 8139745
TI  - Plasma amino acid profile in the elderly with increasing uraemia.
AB  - Abnormalities in plasma amino acid profiles have been reported in severe uraemia
      and dialysis patients and may be a consequence of altered protein metabolism in
      the presence of metabolic acidosis. We studied plasma amino acid profiles in 7
      control subjects [GFR 92.7 +/- (SEM) 14.5 ml/min/1.73 m2] and 7 elderly patients
      with renal failure (GFR 16.5 +/- 1.3 ml/min/1.73 m2). Uraemic patients had
      significantly reduced plasma levels of valine, tyrosine, phenylalanine,
      tryptophan and elevated histidine compared to controls. There was no correlation
      between arterial pH or bicarbonate and plasma amino acid levels.

PMID- 8139746
TI  - HCV viruses: a new problem in pediatric dialysis patients?

PMID- 8139747
TI  - Remission of nephrotic syndrome on lovastatin treatment.

PMID- 8139748
TI  - Detection of antineutrophil cytoplasmic antibodies in the classic form of
      hemolytic uremic syndrome.

PMID- 8139749
TI  - End-stage renal disease after necrotising glomerulonephritis in an elderly
      patient with temporal arteritis.

PMID- 8139750
TI  - Minimal change glomerular disease in association with a carcinoma of the
      esophagus.

PMID- 8139751
TI  - Transarterial fibrinolysis using tissue plasminogen activator in a patient with
      acute renal failure due to acute thrombosis of bilateral renal arteries. 3 years'
      follow-up.

PMID- 8139752
TI  - Rhabdomyolysis and acute renal failure in a heart transplant recipient treated
      with hypolipemiants.

PMID- 8139753
TI  - A case of immune complex glomerulonephritis associated with pulmonary
      cryptococcosis.

PMID- 8139754
TI  - Results of renal transplantation using living-related HLA-identical donors.

PMID- 8139755
TI  - Effect of penicillin on GABA-gated chloride ion influx.
AB  - To investigate the mechanism of penicillin-induced convulsions, we have studied
      the effects of penicillin G (PC-G) on GABA-gated chloride ion influx in brain
      'microsac' preparations of mice. In the presence of 10(-4) M GABA, PC-G inhibited
      GABA-gated chloride ion influx in a dose-dependent manner. The dose-response
      curve for GABA in the presence of 10(-3) M PC-G was shifted rightward and there
      was a decrease in maximum response. The inhibitory effects of PC-G were not
      reversed by RO 15-1788, an antagonist of benzodiazepine (BZ) receptors, but were
      reversed by washing the 'microsac' membranes. Therefore, PC-G probably exerts its
      proconvulsant effect by inhibiting GABA-gated chloride ion influx. However, it
      appears not to act through the BZ receptor of the GABA/BZ receptor complex.

PMID- 8139756
TI  - Serine protease inhibitors block N-terminal arginylation of proteins by
      inhibiting the arginylation of tRNA in rat brains.
AB  - The tRNA mediated, posttranslational, N-terminal arginylation of proteins occurs
      in all eukaryotic cells. In nervous tissue, these reactions can be inhibited by
      endogenous molecules with a molecular weight of between one thousand and five
      thousand. In the present experiments, exogenous serine protease inhibitors (10(
      5) M or less) but not other types of protease inhibitors, were found to be able
      to block the arginylation of protein in extracts of rat brain homogenates.
      Inhibition was not by the usual mode of action of protease inhibitors, but by
      interfering (non-competitively) with the charging of tRNA. Since arginylated
      proteins are rapidly ubiquitinated and degraded by cytosolic proteases, serine
      protease inhibitors may act to stabilize proteins by a dual mechanism of
      inhibiting arginylation as well as inhibiting serine proteases.

PMID- 8139757
TI  - Inhibitory effects of tryptamine on tolbutamide-induced hypoglycemia in mice:
      mediation by 5-HT receptors.
AB  - Effects of tryptamine on tolbutamide-induced hypoglycemia were investigated in
      mice. Tryptamine significantly inhibited hypoglycemia elicited by tolbutamide.
      The inhibitory effects of tryptamine were strongly blocked by the 5-HT1 and 5-HT2
      receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin,
      while the 5-HT3 receptor antagonist ICS 205-930 was without effect. Tryptamine
      induced hyperglucagonemia in tolbutamide-treated mice, and this effect elicited
      by tryptamine was strongly inhibited by the 5-HT2 receptor antagonist ketanserin.
      These results suggest that the inhibitory effects of tryptamine on tolbutamide
      induced hypoglycemia are mediated by 5-HT2 receptors and that tryptamine is
      involved in glucagon release.

PMID- 8139758
TI  - Utilization of mannose by astroglial cells.
AB  - Uptake and metabolism of mannose were studied in astroglia-rich primary cultures
      derived from neonatal rat brains. A saturable component of mannose uptake was
      found with half-maximal uptake at 6.7 +/- 1.0 mM mannose. In addition, a non
      saturable component dominated the uptake at high concentrations of mannose.
      Glucose, cytochalasin B, or phloretin in the incubation buffer inhibited the
      carrier-mediated uptake of mannose. Within the astroglial cells mannose is
      phosphorylated to mannose-6-phosphate. In cell homogenates, the KM value of
      mannose-phosphorylating activity was determined to be 24 +/- 7 microM. The Vmax
      value of this activity is only 40% that of glucose-phosphorylating activity.
      Mannose-6-phosphate was converted to fructose-6-phosphate by mannose-6-phosphate
      isomerase. The specific activity of this enzyme in homogenates of astroglial
      cultures was higher than that of hexokinase. Two products of mannose utilization
      in astroglial cells are glycogen and lactate. The amounts of each of these
      products increased with increasing concentrations of mannose. In contrast to the
      generation of lactate, that of glycogen from mannose was enhanced in the presence
      of insulin. In conclusion, we suggest that mannose is taken up into the cells of
      astroglia-rich primary cultures by the glial glucose transporter and is
      metabolized to fructose-6-phosphate within the astroglial cells.

PMID- 8139760
TI  - Binding characteristics of [3H]flunitrazepam in pentobarbital-withdrawal rats.
AB  - The effects of chronic pentobarbital (PB) treatment on the binding
      characteristics of [3H]flunitrazepam (FLU) in rat brain were examined. Saline or
      sodium PB (500 micrograms/10 microliters/hr) was infused into the lateral
      cerebral ventricles of rats for 6 days using osmotic pumps. Immediately before
      withdrawal, there were no significant differences in [3H]FLU binding constants
      (KD and Bmax) between saline and PB groups. However, 24 hr withdrawal caused an
      increase in Bmax with no changes in KD. The enhancement of [3H]FLU binding by in
      vitro addition of chloride ions and PB was not affected after the PB infusion.
      The PB enhancement of [3H]FLU binding was inhibited by the convulsant,
      picrotoxinin. PB withdrawal did not cause significant differences in the binding
      constants of [3H]Ro 15-1788, a benzodiazepine (BZ) antagonist, between the saline
      and PB groups. Pretreatment of membranes with 0.02 mM of 3-[(3-cholamidopropyl)
      dimethylammonio]-1- propanesulfonate (CHAPS), a zwitterionic detergent, caused
      decreases in both KD and Bmax in FLU binding in PB-withdrawal membrane, but not
      in the saline-treated membrane. The enhancement of [3H]FLU binding by chloride
      ions and PB was not affected by the CHAPS treatment. These results suggest that
      the change in BZ receptors induced by PB withdrawal is functionally linked to the
      GABA-BZ-barbiturate receptor complex and that PB withdrawal induces some
      conformational changes in BZ receptors.

PMID- 8139759
TI  - Association of glucocerebroside homolog biosynthesis with Schwann cell
      proliferation.
AB  - The biosynthesis of myelin-associated glycolipids was studied in quiescent
      secondary cultures of Schwann cells and in rapidly proliferating population of
      transfected Schwann cells (TSC) by in vitro incorporation of [3H]galactose. The
      TSC demonstrated a marked increase (> 10-fold) in [3H]galactose incorporation
      when compared to quiescent Schwann cells. The level (or amount) of [3H]galactose
      incorporation into lipids is dependent upon the number of TSC in culture. The
      majority of 3H-labeled lipids were oligohexosylceramides (GL-2, GL-3, and GL-4).
      Substrates that inhibit TSC proliferation, collagen type I and Matrigel, and
      artificial basement membrane, decrease the [3H]galactose incorporation by 25% and
      80%, respectively. Our results indicate that the synthesis of glucocerebroside
      and its homologs is associated with Schwann cell proliferation.

PMID- 8139761
TI  - Purification and properties of a glycerophosphocholine phosphodiesterase from
      bovine brain myelin.
AB  - An enzyme releasing phosphocholine from glycerophosphocholine was purified to
      apparent homogeneity based upon SDS-PAGE. The enzyme was liberated from
      lyophilized bovine myelin by differential detergent extraction and final
      purification was accomplished with Q-Sepharose Fast Flow chromatography yielding
      an apparently homogeneous protein. The molecular mass based upon PAGE was
      approximately 14 kDa. The enzyme was also capable of releasing p-nitrophenol from
      p-nitrophenyl-phosphocholine. Maximal activity was obtained with 0.2 mM ZnCl2 or
      1 mM CoCl2. p-Nitrophenylphosphocholine and phosphocholine were competitive
      inhibitors of glycerophosphocholine hydrolysis with Ki's of 0.028 mM and 0.03 mM
      respectively. Glycerophosphocholine and phosphocholine were competitive
      inhibitors of p-nitrophenylphosphocholine hydrolysis with Ki's of 0.5 mM and 1.75
      mM respectively.

PMID- 8139762
TI  - Effects of cocaine on sodium dependent dopamine uptake in rat striatal
      synaptosomes.
AB  - Initial velocity of uptake of dopamine (DA) has been measured in the presence of
      1 microM cocaine as a function of both [DA] and [Na]. Although DA uptake is
      overwhelmingly dependent on sodium, it appears that a small amount of DA uptake
      takes place in the absence of sodium. This contrasts with a previous study of the
      sodium dependence of uptake without cocaine (referred to below as control), in
      which uptake was found to be 100% sodium dependent. The data were fitted to
      several rapid equilibrium models and the minimal best fit model identified. The
      interaction of transporter (C), DA (S), and Na+ (Na) in this present model is
      identical to the reaction scheme found previously to fit control data (no
      cocaine). Whereas the control model required translocation only as CNa2S, in the
      presence of cocaine (I), two additional translocated species are required to fit
      the data (CS and CNaS). Another previous study of the interaction of carrier and
      cocaine at a constant [Na]0 predicted that cocaine interacts with a transporter
      site other than the DA binding site and that uptake takes place as CS and CSI.
      The present results are consistent with the assumption that the CS and CNaS forms
      of the present model are actually CSI and CNaSI, since they are required to fit a
      model of the sodium dependence in the presence of cocaine, but are not required
      in the absence of cocaine.

PMID- 8139763
TI  - Effects of low- and high-dose tranylcypromine on [3H]tryptamine binding sites in
      the rat hippocampus and striatum.
AB  - Chronic studies were initiated in rats to determine the effects of high- and low
      dose tranylcypromine (TCP) on [3H]tryptamine (3H-T) binding sites. Male Sprague
      Dawley rats were administered TCP (0.5 or 2.5 mg/kg/day) or vehicle (distilled
      water) for 4, 10 or 28 days via Alzet minipumps. After decapitation, the
      hippocampus and striatum were used to prepare membrane fragments for single point
      3H-T binding. Hippocampal 3H-T binding was reduced after 10 and 28 days with the
      low dose and after 4, 10 and 28 days with the high dose. Striatal 3H-T binding
      was reduced by both doses at all time intervals. The high dose resulted in a
      significantly greater reduction in striatal 3H-T binding than did the low-dose
      after 4, 10, and 28 days. These results suggest that a more rapid reduction of 3H
      T binding in the hippocampus and/or a greater reduction of 3H-T binding in the
      striatum by high-dose TCP than by low-dose TCP may be contributing factors in the
      reported efficacy of the former in refractory depression.

PMID- 8139764
TI  - Inhibition of bioenergetics alters intracellular calcium, membrane composition,
      and fluidity in a neuronal cell line.
AB  - The effect of inhibited bioenergetics and ATP depletion on membrane composition
      and fluidity was examined in cultured neuroblastoma-glioma hybrid NG108-15 cells.
      Sodium cyanide (CN) and 2-deoxyglucose (2-DG) were used to block, oxidative
      phosphorylation and anaerobic glycolysis, respectively. Endoplasmic reticulum
      (ER) Ca(2+)-pump activity measured by 45Ca2+ uptake was > 92% inhibited in intact
      cells incubated with CN (1 mM) and 2-DG (20 mM) for 30 min. In addition, exposure
      of cells to CN and 2-DG caused a 134% increased release of isotopically labeled
      arachidonic acid (3H-AA) or arachidonate-derived metabolites from membranes.
      Removal of Ca2+ from the incubation medium ablated the CN/2-DG induced release of
      3H-AA or its metabolites. Membrane fluidity of intact cells was measured by
      electron spin resonance spectroscopy using the spin label 12-doxyl stearic acid.
      The mean rotational correlation time (tau c) of the spin label increased 49% in
      CN/2-DG exposed cells compared to controls, indicating a decrease in membrane
      fluidity. These results show that depletion of cellular ATP results in inhibition
      of the ER Ca(2+)-pump, loss of AA from membranes, and decreased membrane
      fluidity. We propose that impaired bioenergetics can increase intracellular Ca2+
      as a result of Ca(2+)-pump inhibition and thereby activate Ca(2+)-dependent
      phospholipases causing membrane effects. Since neurons derive energy
      predominantly from oxidative metabolism, ATP depletion during brain hypoxia may
      initiate a similar cytotoxic mechanism.

PMID- 8139765
TI  - Thyroid hormones influence the astroglial plasticity: changes in the expression
      of glial fibrillary acidic protein (GFAP) and of its encoding message.
AB  - Normal development of the brain requires the presence of thyroid hormones. To
      progress in the understanding of the contribution of astrocytes to brain
      pathophysiology we investigated the effect of T3, on the astroglial plasticity
      through the expression of two astroglial proteins: the Glial fibrillary acidic
      protein (GFAP) and the glutamine synthetase (GS). Western and northern blots were
      performed using astroglial primary cultures initiated from neocortex and
      cerebellum of new-born mice. Treatment with T3 caused a decrease of GFAP and of
      its encoding message level in both areas, suggesting a transcriptional regulation
      of its expression, whereas it had no apparent effect on GS expression. This
      reduction in GFAP expression was developmentally regulated; it was significant in
      proliferating but not in more mature astrocytes. T3 effect on astrocytes was
      higher in the cerebellum compared to the neocortex, suggesting the presence of
      astroglial subpopulations differing by their sensitivity to T3. The astroglial
      specific response to T3, corresponds to a precise, targetted and regulated
      adaptation of the cell. Factors of the microenvironment may modulate this
      specific astroglial response in vivo.

PMID- 8139766
TI  - Effects of chelators on iron uptake and release by the brain in the rat.
AB  - The iron chelators desferrioxamine (DFO), pyridoxal isonicotinoyl hydrazone
      (PIH), 2,2'-bipyridine, diethylenetriamine penta-acetic acid (DTPA) and 1,2
      dimethyl-3-hydroxy pyrid-4-one (CP20) were analysed for their ability to change
      59Fe uptake and release from the brain of 15- and 63-day rats either during or
      after intravenous injection of 59Fe-125I-transferrin. DTPA was the only chelator
      unable to significantly reduce iron uptake into the brain of 15-day rats. This
      indicates that iron is not released from transferrin at the luminal surface of
      brain capillary endothelial cells. CP20 was able to reduce iron uptake in the
      brain by 85% compared to 28% with DFO. Only CP20 was able to significantly reduce
      brain iron uptake in 63 day rats. Once 59Fe had entered the brain no chelator
      used was able to mediate its release. All of the chelators except CP20 had
      similar effects on femur iron uptake as they did on brain uptake, suggesting
      similar iron uptake mechanisms. It is concluded that during the passage of
      transferrin-bound iron into the brain the iron is released from transferrin
      within endothelial cells after endocytosis of transferrin.

PMID- 8139767
TI  - Taurine in the developing cat: uptake and release in different brain areas.
AB  - Taurine is an important modulator of neuronal activity in the immature brain. In
      kittens, taurine deficiency causes serious dysfunction in the cerebellar and
      cerebral visual cortex. The processes of taurine transport in vitro were now
      studied for the first time in different brain areas in developing and adult cats.
      The uptake of taurine consisted initially of two saturable components, high- and
      low-affinity, in synaptosomal preparations from the developing cerebral cortex
      and cerebellum, but the high-affinity uptake component completely disappeared
      during maturation. The release of both endogenous and preloaded labeled taurine
      from brain slices measured in a superfusion system was severalfold stimulated
      with a slow onset by depolarizing K+ (50 mM) concentrations. K+ stimulation
      released markedly more taurine from the cerebral cortex, cerebellum and brain
      stem in kittens than in adult cats. The responses were largest in the cerebellum.
      Both uptake and release of taurine are thus highly efficient in the brain of
      kittens and may be of significance in view of the vulnerability of cats to
      taurine deficiency.

PMID- 8139768
TI  - Subcellular distribution of carbonic anhydrase and Na+,K(+)-ATPase in the brain
      of the hyt/hyt hypothyroid mice.
AB  - Activities of carbonic anhydrase and Na+,K(+)-ATPase in tissue homogenates and in
      subcellular fractions from different brain regions were studied in inherited
      primary hypothyroid (hyt/hyt) mice. The body weight, the weight of different
      brain regions, and the plasma thyroxine and triiodothyronine levels of hyt/hyt
      mice were significantly lower than those of the age-matched hyt/+ controls. In
      tissue homogenates of cerebral cortex, brain stem and cerebellum of hypothyroid
      mice, the activity of carbonic anhydrase (units/mg protein) was 59.2, 57.6, and
      43.2%, and the activity of Na+,K(+)-ATPase (nmol Pi/mg protein/min) was 73.7,
      74.4 and 68.7%, respectively, of that in corresponding regions of euthyroid
      littermates. The decrease in enzyme activity in tissue homogenates was also
      reflected in different subcellular fractions. In cerebral cortex and brain stem,
      carbonic anhydrase activity in cytosol, myelin and mitochondrial fractions of
      hypothyroid mice was about 45-50% of that in euthyroid mice, while in cerebellum
      the carbonic anhydrase activity in these subcellular fractions of hyt/hyt mice
      was only 33-38% of that in hyt/+ controls. Na+,K(+)-ATPase activity in myelin
      fraction of different brain regions of hyt/hyt mice was about 34-42% of that in
      hyt/+ mice, while in mitochondria, synaptosome and microsome fractions were about
      44-52, 46-53, and 66-68%, respectively of controls. These data indicate that the
      activity of both carbonic anhydrase and Na+,K(+)-ATPase was affected more in the
      myelin than other subcellular fractions and more in the cerebellum than cerebral
      cortex and brain stem by deficiency of thyroid hormones.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8139770
TI  - Incorporation of [3H]ethanolamine into acetylcholine by a human cholinergic
      neuroblastoma clone.
AB  - Human neuroblastoma cholinergic LA-N-2 cells were used as an experimental model
      to test the possibility that the methylation of phosphoethanolamine (PEtn) to
      phosphocholine (PCho) and free choline (Cho) (Andriamampandry et al. 1989) could
      contribute to acetylcholine (AcCho) synthesis. LA-N-2 cells were incubated with
      [3H]Cho for 90 min and 22.7% of the radioactivity was present in PCho, 18.5% in
      free Cho and 4.8% as AcCho. The ratio of Cho/AcCho, however, was of about 1 after
      16 hours of incubation. The incorporation of 10 microM [3H]ethanolamine (Etn)
      into MeEtn, PMeEtn, PMe2Etn and their corresponding phospholipids was reduced in
      cells incubated in medium containing 7.2 microM choline as compared to cells
      incubated in medium devoid of choline indicating that the lack of Cho from the
      incubation medium stimulated the conversion of PEtn to Cho water soluble
      derivatives. Incubation of LA-N-2 cells with [3H]Etn led to the labelling of
      [3H]AcCho. Cultures incubated in parallel with [3H]Cho showed that roughly 10% of
      [3H]AcCho obtained after 16 hrs of incubation with the Cho label derived from
      [3H]Etn. The synthesis of Cho and AcCho from Etn may be enhanced after cellular
      differentiation induced by the growth of the cells in the presence of retinoic
      acid (RA). The results indicate that the methylation of [3H]Etn and/or of
      [3H]PEtn may be used by cholinergic neurons as precursor for AcCho.

PMID- 8139769
TI  - The role of cytosolic free calcium in the regulation of pyruvate dehydrogenase in
      synaptosomes.
AB  - Calcium homeostasis and mitochondrial oxidative metabolism interact closely in
      brain and both processes are impaired during hypoxia. Since the regulation of the
      pyruvate dehydrogenase complex (PDHC) may link these two processes, the relation
      of cytosolic free calcium ([Ca2+]i) to the activation state of PDHC (PDHa) was
      assessed in isolated nerve terminals (i.e. synaptosomes) under conditions that
      alter [Ca2+]i. K+ depolarization elevated [Ca2+]i and PDHa and both responses
      required external calcium. Treatment with KCN, an in vitro model of hypoxia
      decreased ATP and elevated [Ca2+]i and PDHa. Furthermore, in the presence of KCN,
      PDHa became more sensitive to K+ depolarization as indicated by larger changes in
      PDHa than in [Ca2+]i. The calcium ionophore Br-A23187 elevated [Ca2+]i, but did
      not affect PDHa. K+ depolarization elevated [Ca2+]i and PDHa even if [Ca2+]i was
      elevated by prior addition of ionophore or KCN. Previous in vivo studies by
      others show that PDHa is altered during and after ischemia. The current in vitro
      results suggest that hypoxia, only one component of ischemia, is sufficient to
      increase PDHa. These data also further support the notion that PDHa is regulated
      by [Ca2+]i as well as by other factors such as ATP. Our results are consistent
      with the concept that PDHa in nerve endings may be affected by [Ca2+]i and that
      these two processes are clearly linked.

PMID- 8139771
TI  - Brain myelin-bound Zn(2+)-glycerophosphocholine cholinephosphodiesterase is a
      glycosylphosphatidylinositol-anchored enzyme of two different molecular forms.
AB  - An Zn(2+)-GPC cholinephosphodiesterase activity, which is present more
      predominantly in myelin than in microsome or cytosol, has been examined using rho
      nitrophenylphosphocholine as a substrate. In the solubilization of enzyme
      activity from myelin membranes, lysolecithin was found to be more effective than
      Triton X-100 or deoxycholate. Especially, the myelin-bound phosphodiesterase was
      suggested to be a glycosylphosphatidyl-inositol-anchored protein, based on
      solubilization by B. cereus phospholipase C and Triton X-114 phase separation.
      Interestingly, it was found that while phospholipase C-solubilized enzyme, a
      hydrophilic protein, was associable with Concanavalin A column, detergent
      solubilized amphiphilic form of enzyme was not. Either detergent extract or
      cytosol was observed to contain both amphiphilic form and hydrophilic one. In CM
      sephadex chromatography, the soluble hydrophilic phosphodiesterase was observed
      to be separatable into two forms of enzyme. In comparative studies, both forms of
      phosphodiesterase showed much similarity in substrate specificity, optimum pH, Km
      value and Zn2+ requirement, although they differed in charge property and
      molecular weight.

PMID- 8139772
TI  - [A new method for calculating the mass of the left ventricle by
      angiocardiography].
AB  - The authors describe a simplified method to determine left ventricular volume and
      mass from the ventricular silhouette, taken from a right oblique anterior
      angiographic projection at 30 degrees, used to measure the telediastolic surface
      and major axis, and of measuring the telediastolic thickness of the ventricular
      wall in the postero-lateral segment of the silhouette taken from a left oblique
      anterior angiographic projection at 60 degrees. Sixty-four ventricular
      silhouettes were analysed in patients undergoing left kineventriculography for
      coronaropathy and ventricular mass was determined using both the new and
      traditional methods. Using the new method mass values (mean value 87.85 g/sq.mt.
      and SD 34.04) were obtained which were significantly correlated (r = 0.999) with
      values obtained using the standard method (mean value 88.02 g/sq mt and SD
      34.11). The practical advantages of the new method are discussed (simplicity of
      calculating equation without determining the minor axis of the ventricular
      silhouette), together with its limits due to the monoplanar technique used to
      calculate the volume and the measurement of wall thickness in those cases in
      which the postero-lateral wall is considered the most representative of the mean
      thicknesses of the left ventricular wall. Lastly, the paper discusses the
      possibility of applying this method to non-invasive procedures, such as the two
      dimensional echocardiogram, where more reliable mass values could be obtained
      even in the event of non-uniform wall thickness.

PMID- 8139773
TI  - Evaluation of left and right ventricular function by transesophageal
      echocardiography.
AB  - Transesophageal echocardiography, especially in the emerging generation of
      biplane and multiplane probes with the availability of continuous wave Doppler,
      has increased our capability for evaluating intracardiac hemodynamics and
      ventricular function. Transesophageal studies have expanded their role both in
      clinical research and routine monitoring. The available hemodynamic data
      (assessment of left and right ventricular function, estimation of left atrial and
      pulmonary artery pressures, evaluation of the hypotensive patient) apply not only
      to patients monitored in the operating room but also to patients in the critical
      care and ambulatory setting. These data can be combined with the anatomic
      pathology to provide bedside diagnoses and often facilitate appropriate therapy.
      Further improvements in the quality of both images and computer software are
      likely to allow more detailed studies of subtle changes in cardiac function in
      humans.

PMID- 8139774
TI  - [The incidence of acute myocardial infarct during the week. A chronobiological
      evaluation].
AB  - Several diseases, and particularly cardiovascular affections, show a periodic
      fluctuation in their occurrence. We investigated acute myocardial infarction
      (AMI) incidence in connection with the day of the week, looking for a link with
      psycho-social phenomena. Eight hundred and fifty-two patients with AMI were
      considered: they had been admitted to the emergency department of two main towns
      of northeastern Italy during a calendar year. Eight hundred and seventeen (533
      men, 284 women) were eligible for the purpose of this study. The time of symptom
      onset was recorded, cardiovascular risk factors and occupational condition were
      evaluated. All data were analyzed through chi-square test of uniformity and
      Halberg single cosinor test. No statistically significant difference from the
      uniform distribution appeared in acute events occurrence both in patients as a
      whole and in single subgroups subdivided according to gender and age. However,
      the preferential distribution during the days of the week was somewhat different
      between men (highest incidence at the extreme of the week) and women (highest
      incidence about mid-week). Statistically significant differences in AMI
      occurrence in the week were evidenced when patients were analyzed after
      subdivision according to their occupational condition: working subjects, in
      comparison with not-working individuals, showed a higher AMI incidence at the
      beginning of the week with respect to subsequent days. It is therefore likely
      that the stress associated with the return to work (according to the weekly
      working pattern of western society) represents an additional important cause of
      AMI. The mechanisms for that are only speculative.

PMID- 8139775
TI  - [Cigarette smoking and acute myocardial infarct].
AB  - The study examined a group of 150 patients with acute myocardial infarction aged
      under 60 years old. The subjects examined were divided into smokers and non
      smokers; smokers were further subdivided into three groups: those smoking less
      than 20, between 20 and 40 and more than 40 cigarettes a day. Furthermore, they
      were divided into two groups aged under or over 40. The following parameters were
      evaluated and compared: the method of onset of acute myocardial infarction, the
      site of infarction, the presence or absence of the Q wave on the ECG, the
      presence of angina before and after acute myocardial infarction, arrhythmia
      during the acute phase and during hospitalisation, mortality during the first 10
      days of hospitalisation. The results showed that cigarette smoking is a major
      risk factor able to influence the age of onset of acute myocardial infarction,
      especially if over 20 cigarettes a day, whereas it has no influence on clinical
      history and early death.

PMID- 8139776
TI  - [Resistant and pseudoresistant hypertension: an analysis of 10 cases of
      pseudoresistance].
AB  - Hypertension resistant to pharmacological treatment may be caused by various
      factors. Next to the real refractory forms, there is one of false resistance
      known as "pseudoresistance". Pseudoresistance is a condition with a discrepancy
      between blood pressure values measured at the physician's office, which appear
      falsely high, compared to those measured at home by the patient or with the 24
      hour ambulatory blood pressure monitoring which appear to be within the normal
      range. We have studied 10 pseudoresistant patients and valued their average
      pressures measured at the doctor's office (158/96 mmHg), comparing them with
      those measured at home by the patients or family members (135/83 mmHg) and with
      those measured with 24 hour PA monitoring with Takeda monitor mod. 2420 (average
      values of daytime pressure 129/79 mmHg). The difference between values at the
      physician's office and those measured with the 24 hour ambulatory blood pressure
      monitoring have resulted statistically significant (p < 0.0001). In all those
      patients with hypertension treated pharmacologically we recommend the use of 24
      hour ambulatory blood pressure monitoring, so as to evaluate realistically the
      efficacy of the therapy itself and to identify other potential "pseudoresistant"
      individuals.

PMID- 8139777
TI  - [Aortoenteric fistulae. Diagnosis, therapy, results].
AB  - A series of 26 aortoenteric fistulas, 8 primary (PAEF) communications between
      abdominal aorta and gastrointestinal tract and 18 secondary (SAEF) communications
      between aortic graft and intestine, is reported. PAEF is commonly due to
      aneurysmal rupture into the intestine, while SAEF is an uncommon complication of
      abdominal aortic reconstructive surgery. Male to female ratio was 3:1 among the
      PAEF group and 8:1 among the SAEF one. Seven of the PAEF subjects underwent
      urgent surgical operation: 6 enteral defect closure and prosthetic aortic
      replacement. One patient underwent ileal resection and hypogastric artery
      ligation. Survival rate in this group was 42% (3/7). Among the 18 subjects
      affected with SAEF after intestinal repair, vascular procedures were 8 aortic
      graft removal and extra-anatomic bypass grafting, 4 aortic graft removal and
      aortic stump ligation, 5 anastomotic repairs and 1 prosthetic branch
      substitution. Survival rate among this group was 39% (7/18). No differences in
      outcome were noted in this series depending on type of operation, according to
      the literature. The authors conclude that surgical outcome is affected by the
      presence of severe infection not dominated by antibiotics rather than by surgical
      technique. In this series survival rate among the patients with negative
      bacterial culture of the surgical specimen raised up to 80%, while it decreased
      to 20% among subjects harboring septic retroperitoneal collection and graft
      infection.

PMID- 8139778
TI  - [Prosthetic separation in the retroperitoneum in reconstructive arterial
      surgery].
AB  - In this assay we take into consideration 3410 retroperitoneal prosthetic
      reconstructions in aorto-iliac pathology performed in the last 25 years at the
      General and Cardiovascular Institute of Milan. Thirty-nine retroperitoneal
      prosthetic dehiscences were observed; 35 of them had been subjected to their
      first operation in our Institute (1.03%). The incidence of vasculo-enteric
      fistula and pseudoaneurysm seem to decrease in the last 8 years up to 0.9 (0.9%).
      Authors consider etiologic factors, diagnostic procedures and technical
      approaches to this severe complication of vascular surgery.

PMID- 8139779
TI  - [The effects of treatment with atenolol and benazapril on 24-hour pressure
      variability].
AB  - One of the functions of the sympathetic nervous system is to produce a short-term
      increase in blood pressure. It might be thought, therefore, that antihypertensive
      drugs which interfere with the functioning of the sympathetic nervous system
      (e.g. betablockers) would reduce blood pressure variability over 24 h whereas
      those that act independently of it (e.g. ACE inhibitors) would not. Two groups of
      10 hypertensives underwent noninvasive 24-h blood pressure monitoring before and
      after antihypertensive treatment with a betablocker (atenolol) and an ACE
      inhibitor (benazepril) respectively. Blood pressure variability was measured by
      the variability coefficient (standard deviation/mean). Atenolol induced a non
      statistically significant decrease in blood pressure variability, whereas
      benazepril caused a statistically significant increase in systolic blood pressure
      variability. Therefore, we conclude that the evaluation of ACE-inhibitor
      therapeutic effect on blood pressure by the "casual" measurement can be
      misleading in judging the efficacy of such drugs.

PMID- 8139780
TI  - [Left intraventricular thrombosis causing an embolism to the right leg during an
      acute myocardial infarct. A report of a case monitored echocardiographically with
      diagnostic and therapeutic comments].
AB  - Report of a case of a 54-year-old man who, during acute anterior myocardial
      infarction developed an apical thrombus and an embolism of the right leg. The
      serial echocardiographic study demonstrates how the original shape of the
      thrombus acutely changed at the same time of the embolic episode and how the new
      morphology of the thrombotic mass after embolism and thrombolytic plus
      anticoagulant therapy (performed for the acute ischaemic episode of the leg) was
      widely different from the initial one. The role of cross-sectional
      echocardiography is emphasized for the diagnostic value in case of
      intraventricular thrombi and for possible utilization also for therapeutic
      guidance.

PMID- 8139781
TI  - [The enzymatic and electrocardiographic changes falsely indicative of an acute
      myocardial infarct during hypothyroidism].
AB  - Estimation of the enzymes CPK and LDH, with their isoenzymes, is useful in
      diagnosing myocardial infarction and monitoring its progress. However, increases
      of CPK-MB and LDH1, may be not associated with acute myocardial infarction, as in
      hypothyroidism, muscular dystrophy, polymyositis, malignant disease. We report a
      case of hypothyroidism with increased CPK-MB and LDH1. At the beginning the
      diagnosis was difficult because of altered electrocardiogram associated with one
      event of "burning" localized altered at the anterior thorax. This case
      illustrates that plasma enzyme activity and isoenzyme profiles should be
      interpreted with caution when clinical and instrumental (eco 2D) findings are not
      entirely associated with myocardial infarction.

PMID- 8139782
TI  - Brief report: 2D-echo diagnosis of interventricular septal perforation by a
      temporary pacing electrode.
AB  - We report the case of an 83-year-old patient affected by hypertensive cardiopathy
      and admitted to our Division for left ventricular failure and complete
      atrioventricular block; a temporary electrode was inserted via the right internal
      jugular vein. A routine 2D-echo examination performed one day later clearly
      showed the catheter tip in the left ventricular cavity; the interventricular
      septal perforation was confirmed by the presence of right bundle branch block
      pattern on surface electrocardiogram. The following clinical course was totally
      event-free and the patient eventually underwent permanent pacing. A comparison
      with the few cases of pacing-related myocardial perforations so far described by
      the literature is made.

PMID- 8139783
TI  - [The diagnosis and treatment of mobile thrombi in the right heart chambers during
      pulmonary embolism. A report of 3 cases].
AB  - We report the clinical, echocardiographic and therapeutic aspects of three cases
      of right cardiac migrant thromboembolus in pulmonary embolism. The 2D echo was
      always evocative of freely floating migrant thromboembolus in the right cardiac
      chambers. Medical therapy consisted of tissue plasminogen activator in two
      patients, and only calcic heparin and salicylic acid in one patient because of
      contraindications for a more aggressive therapy. Progressive reduction of
      thromboembolus until its disappearance was observed by echo 2D in two patients
      some hours after rt-PA administration, in one patient seven days after therapy
      with calcic heparin and salicylic acid. Echo 2D may be important test in
      diagnosis pulmonary embolism when perfusion lung (extremely sensitive but non
      specific test) or pulmonary angiography (the most accurate test) are not
      available at pulmonary angiography (the most accurate test) are not available at
      hospital and patient cannot be transferred for his critical illness. Fibrinolytic
      therapy seems extremely effective if administered early.

PMID- 8139784
TI  - [Radical hysterectomy. Operative complications].
AB  - The Authors carried out a retrospective examination of data relating to 241
      patients undergoing radical hysterectomy with pelvic lymphadenectomy between 1970
      and 1991. The basic aim of the study was to identify and quantify complications
      correlated to radical hysterectomy using the Wertheim-Meigs method. Surgery was
      performed in 223 cases due to cervical cancer, in 13 cases due to endometrial
      cancer, in 3 cases due to vaginal cancer and in 2 due to ovarian cancer with
      secondary extension to the uterus. Complications were subdivided into
      intraoperative and postoperative. Intraoperative complications involved the
      urinary tract in 4.5% and other apparatus (intestinal and nervous lesions,
      hemorrhage due to vascular damage) in 8.7% of cases. Postoperative complications
      were classified as follows: 35.2% involving the urinary tract (fistula 20.3% and
      vesical dysfunction 14.9%) and 8% involving other organs or systems (infections,
      neuropathy, pelvic lymphocele, pathologies of intestinal canalization, etc.).
      Lastly, the Authors examined the individual complications of radical
      hysterectomy, focusing attention in particular on vesicourethral dyskinesia, in
      the light of the physiopathological mechanisms reported in the literature. The
      mean rate of complications in the series examined here was substantially
      comparable to that reported by other Authors.

PMID- 8139785
TI  - [Therapy of simple endometrial hyperplasia with GnRH analogs. Evaluation of a
      multicentric ambulatory study. Preliminary results].
AB  - Endometrial hyperplasia is a frequent pathology during menopause and involves the
      risk of malignant transformation of the lesions. In an attempt to avoid radical
      surgery, this study proposes the use of triptorelin which was used to treat 56
      patients with histologically confirmed symptoms of endometrial hyperplasia
      without atypia. GnRH-analog was administered using the intramuscular route every
      28 days for 6 months. Histological controls were carried out 30 days after the
      last injection and showed the resolution of histological symptoms, confirmed
      after three months.

PMID- 8139786
TI  - [Attitudes toward estrogen replacement therapy. Study conducted on a sample
      population of women attending an ambulatory care center for the treatment of
      menopause].
AB  - Hormonal Replacement Therapy (HRT) is the most effective treatment of menopausal
      disturbances and has an established role in reducing the cardiovascular risk and
      in preventing the postmenopausal osteoporosis. Nevertheless several reports have
      evidenced that compliance with hormonal replacement therapy was not as good as
      expected, and that physician's and women's opinions can strongly influence the
      HRT choice, and the continuation of HRT use. The aim of this study was to assess
      the opinions and the expectations of menopausal women toward HRT. PATIENT AND
      METHODS. We utilized a questionnaire exploring social and affective conditions,
      and in particular women's opinions and experiences on menopause, hormonal
      therapy, the possibility of information, the reasons for accepting or refusing
      hormonal therapy. The questionnaires were administered to 226 menopausal clinic
      patients (Menopausal age: 2-10 years) in spontaneous menopause. RESULTS. 28% of
      the women were taking HRT at the time of the survey. Worries about menopause were
      reported by 27.4% of the group; this percentage was similar in both user and non
      user groups. 70% received information on HRT from family doctors, and 63% from
      mass-media or conversations. 70% believes that the main problem of menopause is
      osteoporosis, and its prevention represents the most frequent aim that patients
      feel can be achieved by HRT. 67.5% of the group is afraid that long term
      treatment can be dangerous, however only 57% asked for detailed information to
      the doctor. To the question "Are you informed that HRT can reinduce menstrual
      bleeding?", 57.5% of the patients answered yes; 30% considered it to be a
      problem. CONCLUSIONS. Our study was carried out in a menopausal clinic and this
      can influence the answers of the respondents. Most women received some
      information on HRT, but their knowledge was only partial and did not eliminate
      the unrational fear of hormone therapy. Although long term use of HRT is to
      prevent CVD and menopausal osteoporosis, many of our patients specifically asked
      for treatment to be as short as possible. Women expectations's towards HRT are
      mainly referred to osteoporosis prevention and treatment: this may be explained
      by the high frequency of osteoarticular pain found in our patients; nevertheless
      it is possible that the more rational fear of osteoporosis hides the unconscious
      fear of a dramatic physical breakdown caused by the menopause. Detailed
      information to family doctors, to specialists, and to patients along with a
      further improvement of therapeutic regimens will allow a greater diffusion of
      HRT, bringing its short and long term benefits to an increasing number of women.

PMID- 8139787
TI  - Clinical evaluation of an oral contraceptive containing Ethinyl-Oestradiol (30
      mcg) and Gestoden (75 mcg).
AB  - At the Family Planning Center AIECS in Bari, 383 women have been treated for 6
      cycles with an estroprogestinic combination containing Ethinyl-Oestradiol (30
      mcg) and Gestoden (75 mcg). We evaluated the following parameters: contraceptive
      efficacy, cycle control, side effects and acceptability. At the end of the
      treatment, 346 women (90.4%) decided to continue the treatment while only 22
      expressed a negative opinion. The clinical experience has been positively
      considered by the physician, considering the high contraceptive efficacy, even if
      12% of women forgot to take the pill (Pearl Index 0.00) side effects profile and
      cycle control.

PMID- 8139788
TI  - [Treatment of fibrocystic disease of the breast with myrtillus anthocyanins. Our
      experience].
AB  - The aim of this study was to further research into the therapeutic treatment of
      fibrocystic mastopathy. The study hypothesis included the clinical and
      instrumental control (echography) of patients with FCD before and after at least
      three months treatment with anthocyanosides. The protocol used was of the
      prospective and comparative type, whereas follow-up lasted three months. The
      study was performed in the outpatients' clinic of Breast Physiopathology and
      Echography organised within the ambit of the services of the Gynecology and
      Obstetrics Division. In this particular instance both echography and clinical
      examinations were performed at the same clinic. A total of 257 patients took part
      in the programme of which 35 were excluded since they failed to attend subsequent
      controls. Women were selected on the basis of absence of malignant disease and
      presence of clinical, echographic or mammographic symptoms of fibroso-cystic
      mastopathy. In addition, all women presented mastodynia which made therapy
      indispensable. The socio-demographic: characteristics of the population were
      polymorphous since women were resident not only in the area of USSL 36 but also
      other Italian provinces. The diameter of any lesions found was measured together
      with the thickness of the mammary gland. The thickness was always measured of QSE
      level both before and after treatment. The results were encouraging. There was a
      marked improvement in 75 patients, equivalent to 33.78%, symptoms were reduced in
      61 women (27.47%) and disappeared in 14 (6.30%), whereas treatment had no effect
      in 72 cases (32.43%). In conclusion, echopalpation (clinical examination +
      echography) was extremely valuable in the study of these patients, especially if
      aged under 40. Moreover, therapy for three months in patients with mastodynia,
      consequent to fibrous mastopathy, was efficacious in reducing symptoms and
      mammary tension. At the same time, it is important to emphasise the absence of
      virtual absence of collateral effects to treatment.

PMID- 8139789
TI  - [Paraneoplastic erythema associated with a carcinoma of the cervix. Our
      experience].
AB  - The authors report a case of bullous erythema observed in a young woman affected
      with II B stage carcinoma of the cervix, whose clinical course was likely to be a
      paraneoplastic lesion. The aim of the report is to outline such a rare
      association between a dermatologic pattern and a gynecologic tumor and to
      synthesize the literature's data concerning this matter.

PMID- 8139790
TI  - [Endolymphatic stromal myosis of the uterus. Report of a case].
AB  - A case of endolymphatic stromal myosis is reported, recalling the rarity of this
      pathology. Its relations with other mesenchymal lesions of the uterus and the
      most likely differential diagnoses are considered.

PMID- 8139791
TI  - [Primary non-Hodgkin's lymphoma of the vagina: a rare case].

PMID- 8139792
TI  - [Neurofibromatosis and pregnancy. Considerations on a clinical case and review of
      the literature].
AB  - In this paper, starting from a case of neurofibromatosis adversely affecting
      pregnancy, the authors consider several interactions between pregnancy and Von
      Recklinhausen's diseases. The review of the literature emphasizes either an
      exacerbation of the maternal disease because of pregnancy, or the onset
      appearance of serious complications such as sarcomatous degeneration of
      neurofibromas, activation of a silent pheochromocytoma, rupture of an aneurysm.
      Moreover, the effects of neurofibromatosis on the pregnancy cause an elevated
      risk of IUGR, pregnancy hypertension, abortion and stillbirth and
      oligohydramnios. The pregnancy of a patient affected with neurofibromatosis needs
      careful evaluation of the maternal clinical conditions and of the foetus-placenta
      unity.

PMID- 8139793
TI  - [Acute pancreatitis and pregnancy].
AB  - Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make
      their occurrence, mainly, in the third trimester of gestation. Two cases of acute
      pancreatitis in pregnancy are described; in both cases patients referred healthy
      diet, no habit to smoke and no previous episode of pancreatitis. An obstructive
      pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal
      pain are aspecific symptoms that impose a differential diagnosis with acute
      appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data
      (elevated serum amylase and lipase levels) and ultrasonography carry out an
      accurate diagnosis. The management of acute pancreatitis is based on the use of
      symptomatic drugs, a low fat diet alternated to the parenteral nutrition when
      triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case
      of obstructive pathology of biliary tract, is optimally collected in the third
      trimester or immediately after postpartum. Our patients, treated only medically,
      delivered respectively at 38th and 40th week of gestation. Tempestivity of
      diagnosis and appropriate therapy permit to improve prognosis of a pathology
      that, although really associated with pregnancy, presents high maternal mortality
      (37%) cause of complications (shock, coagulopathy, acute respiratory
      insufficiency) and fetal (37.9%) by occurrence of preterm delivery.

PMID- 8139795
TI  - The weight and fitness status of United States children.
AB  - Although the prevalence of overweight and obesity among US children is a concern
      for many health care professionals, incidence rates over time seem to be
      variable, depending on the assessment measurements used. It is difficult to
      determine the associated health implications of pediatric obesity or overweight,
      especially the type that might result in adult obesity or overweight. This review
      examines the various factors that contribute to the weight and fitness status of
      children, including anthropometric factors, nutrient intake, the level of
      physical activity, and nutrition knowledge. Nutrient intake data of the past
      decade show that the energy and fat intakes of children in the United States have
      been fairly constant. However, data also indicate that their physical activity
      has declined. The data strongly suggest that the apparent prevalence of pediatric
      overweight may not be so much a function of nutrient intake as of a decrease in
      physical activity leading to an imbalance of energy input and output.

PMID- 8139794
TI  - The role of the gut in regulating food intake in man.
AB  - In addition to various psychosocial and metabolic factors, food intake is also
      influenced by gastrointestinal mechanisms that trigger both the initiation and
      termination of eating behaviors. Although gastric distension is one of the most
      obvious signs of "fullness" and clearly plays a role in controlling food intake,
      its effects are only temporary and are distinct from the feelings of satiety
      generally associated with a meal. Such postprandial sensations appear to be
      related to the activation of intestinal chemoreceptors. Other evidence indicates
      that the release of cholecystokinin and perhaps other transmitters as well may
      contribute to satiety. Although the stomach probably does not expand or shrink in
      response to different levels of food intake, nutrient receptors in the small
      intestine probably do adapt to changes in food intake. Intestinal adaptation also
      occurs in response to thyroid hormone, insulin, and cortisol as well as to
      obesity, pregnancy, and illness, which all may have an important bearing on
      changes in eating behavior in these situations.

PMID- 8139796
TI  - Folate, alcohol, methionine, and colon cancer risk: is there a unifying theme?
AB  - Both poor folate status and moderate to excessive alcohol consumption have been
      associated with increased risk of colorectal cancer, although the mechanisms
      through which these effects occur have not been established. A recent report
      suggests that diminished folate status and excessive alcohol intake--which may
      decrease S-adenosylmethionine levels--may induce hypomethylation of DNA, thereby
      promoting colorectal cancer.

PMID- 8139797
TI  - Changing the preference for fat in foods.
AB  - One of the best ways to ensure compliance with a low-fat diet is to reduce the
      preference for fat in foods. A recent study suggested that the hedonic response
      to fat in selected foods declined during 12 weeks on a low-fat diet when sensory
      exposure to fats was absent. No change in fat preference was seen when fat
      mimetics were part of the low-fat diet, suggesting the preference for fat may
      depend on continued exposure to the properties of fat. However, despite the
      persistence of the downward shift in preference for fat in foods reported by the
      low-fat diet group with no discretionary fat, this intake did not lead to a
      reduction in fat intake during a 3-month follow-up period.

PMID- 8139798
TI  - Is PQQ a significant nutrient in addition to its role as a therapeutic agent in
      the higher animal?
AB  - The controversy as to the nutritional status of pyroloquinoline (PQQ) has now
      been broadened to include various animal tissues by evidence of its vitamin
      status in mice, a mammalian PQQ reductase, and evidence that this enzyme
      participates in mechanisms protecting tissues against oxidative stress.

PMID- 8139799
TI  - Extended lactation and loss of bone.
AB  - Bone density in the femur and lumbar spine were measured in nursing women at 2
      weeks, 6 months, and 12 months after birth in a longitudinal study. Bone density
      was not compromised in nonnursing mothers or a group of mothers who breast-fed
      for up to 5 months. Bone density was significantly reduced in an extended
      lactation group (> or = 6 months). However, these findings should not be a
      deterrent to breast-feeding because the evidence suggests that once breast
      feeding is stopped, recovery of bone density can occur.

PMID- 8139800
TI  - Development and current status of home-delivered meals programs in the United
      States: are the right elderly served?
AB  - Federal home-delivered meals programs for the frail elderly began in the United
      States in the 1970s, and during the 1980s the provision of meals to the homebound
      elderly has been expanded through development of state-funded meals programs. The
      time has now come to pose two questions relative to coverage and program impacts.
      These questions are whether the program serves those who are currently most needy
      and whether the meals programs reduce the need for higher levels of care.
      Information available suggests that the elderly most served are those with
      socioeconomic problems that reduce their ability to obtain regular meals. Medical
      disability as a criterion for program eligibility or priority is less often used.
      The new finding that provision of home-delivered meals reduces hospitalization
      rates has to be re-examined, to ask the key question of whether the medically
      needy are actually kept out of the hospital by being provided with home-delivered
      meals.

PMID- 8139801
TI  - Annual update of how each state stands on legislative issues affecting advanced
      nursing practice.

PMID- 8139802
TI  - Strategies for state statutory language changes granting fully independent nurse
      practitioner practice.
AB  - For nurse practitioners (NPs) to be considered as a critical component of health
      care reform, they must change their state statutes to permit independent
      practice. This can be accomplished by plenary prescriptive authority including
      controlled substances. This article provides a summary of NP scope of practice
      and prescriptive privileges to date, together with a discussion of the strong
      statutory language used by Alaska and New Mexico with regard to independent
      practice. Comparisons of model independent scope and prescriptive authority
      statutory language are discussed along with prevalent opposition arguments,
      appropriate practitioner titles, and an enumeration of strategies for effective
      lobbying.

PMID- 8139803
TI  - Chronic obstructive pulmonary disease: current comprehensive care for emphysema
      and bronchitis.
AB  - Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of
      mortality in the United States. Most clients are initially seen when symptomatic
      and significant lung damage has already occurred; most cases are preventable.
      There is no cure for COPD, but lifestyle changes (especially smoking cessation)
      and proper treatment can significantly impact quality of life. The diagnostic
      tools most commonly used include chest x-ray, arterial blood gases, and pulmonary
      function tests. Pharmacologic interventions include steroids, bronchodilators,
      mucolytics, and an armamentarium of antibiotics, which must be selected with
      careful discretion. Because the prognosis of COPD may be guarded, the
      practitioner is obligated to provide information on advance directives. A
      sensitive approach, holistic perspective, consistent follow-up, and clinical
      astuteness are essential ingredients in the management of clients with COPD.

PMID- 8139804
TI  - Interferon-beta 1b: new hope for multiple sclerosis.

PMID- 8139805
TI  - Tacrine approved for cognitive deficits in Alzheimer's disease.

PMID- 8139806
TI  - The human immunodeficiency virus and nonmenstrual toxic shock syndrome: a female
      case presentation.
AB  - Toxic shock syndrome (TSS) generally is associated with tampon use among
      menstruating women. Descriptions from the early 1980's detailed this sudden,
      multisystem, frequently fatal disease. The bacterial agent, Staphylococcus aureus
      produced exotoxins, which were quickly identified as the cause of TSS as well as
      a host of other systemic, bacterial infections. While S. aureus has become one of
      the more common bacterial pathogens in patients with Acquired Immune Deficiency
      Syndrome (AIDS), staphylococcal toxin-related disorders rarely have been reported
      in individuals infected with Human Immunodeficiency Virus (HIV) or individuals
      diagnosed with AIDS. To date all published cases of TSS attendant with HIV
      involved homosexual, hemophiliac, or drug injecting male patients. This report
      describes a woman infected with HIV and diagnosed with the classic array of
      symptoms found in toxic-shock syndrome, and provides information specific to
      women and their experience with HIV infection.

PMID- 8139807
TI  - Federal government focus regarding health care.

PMID- 8139808
TI  - Quality of life: an international commitment.

PMID- 8139809
TI  - Quality of life: an interpersonal perspective.
AB  - Quality of life is a continuum having a higher to lower range. A person's
      perceptions of life quality are time-related and situation-dependent and tend to
      vary according to changing life circumstances. Human relationships, especially
      during the early years of growth and development, can be constructive or
      destructive influences which can color perceptions, expectations, and behavior
      patterns manifested in interpersonal interactions throughout the life span.
      Relationships define and confirm self-worth, identity, acceptance as a human
      being, a sense of belonging, and other essential interpersonal needs.
      Relationships provide social support and tend to reduce stress. The quality of
      interpersonal relationships has a strong bearing on perceptions of quality of
      life.

PMID- 8139810
TI  - Quality of life: sciencing and living the art of human becoming.
AB  - Quality of life, from the person's perspective, is the goal of the human becoming
      theory. Thus far, research on quality of life has been implemented from a
      totality paradigm perspective, excluding consideration of the human as a unitary
      being. The most valuable conclusion to be drawn from all the research is that
      quality of life cannot be quantified. This article specifies a different meaning
      of quality of life and points out ways of sciencing and living the art of nursing
      when quality of life is the goal.

PMID- 8139811
TI  - Intuitive knowing: exposing a myth in theory development.

PMID- 8139812
TI  - Quality of life from a transcultural nursing perspective.
AB  - The author presents research findings derived from Leininger's theory of culture
      care diversity and universality bearing upon quality of life. She holds that
      since quality of life is culturally constituted and patterned, it needs to be
      studied and understood from a transcultural nursing perspective in order to
      advance nursing as a discipline and profession. Five major cultures are presented
      to illustrate culturally constituted dominant care patterns related to quality of
      life. These comparative data reflect more diversity than universality among the
      cultures. The author encourages nurse researchers to move beyond present-day
      overemphasis on individualism and to discover dominant transcultural care values
      and patterns of emic and etic knowledge focused on quality of life, health, and
      well-being.

PMID- 8139813
TI  - Quality of life and goal attainment.
AB  - King's conceptual framework of three dynamic interacting systems (personal,
      interpersonal, social) provides a structure for observing the interacting
      elements that enhance or impinge on quality of life. Interactions and
      transactions with the nurse lead to goal-setting for individuals, families, and
      society. Goal-setting usually leads to goal attainment, which produces
      satisfaction with self and improves one's ability to achieve future success. The
      goal of King's theory (which is derived from her conceptual system) is health for
      individuals, groups, and society. This article explores the use of King's theory
      of goal attainment in maintaining and promoting health, which influences quality
      of life.

PMID- 8139814
TI  - The science of unitary human beings: current perspectives.
AB  - This article explicates current perspectives on Rogers' science of unitary human
      beings. Possibilities for nursing in the 21st century are elaborated upon.
      Attention is called to the increasingly rapid social changes which will have an
      impact on nursing science.

PMID- 8139815
TI  - Chaos theory and some nursing considerations.
AB  - The alleged synthesis of nursing and public health has not produced the expected
      community-as-client emphasis. Public health is characterized as disease-focused,
      with masculine domination, using a causal model. The explanatory model of chaos
      challenges nurses to reexamine nursing's theoretical base by questioning
      assumptions associated with linear thinking. The selected chaotic concepts of
      aperiodicity, attractors, sensitive dependence on initial conditions, phase
      space, and fractals are discussed here. Each concept's connection to physics and
      mathematics is cited and considerations for nursing science are outlined.
      Conclusions include redefining health, nursing, and community in chaotic terms
      and renaming nursing practice, which has this aperiodic and holistic paradigm, as
      ecologic health nursing.

PMID- 8139816
TI  - Focus groups: a data-gathering strategy for nursing research.

PMID- 8139817
TI  - Beyond the threshold: nursing practice in the next millennium.

PMID- 8139818
TI  - Questioning the teacher.

PMID- 8139819
TI  - Use of endosseous implants in treatment of adolescent trauma patients.

PMID- 8139820
TI  - Sexual abuse of the oral cavity in children.
AB  - Child abuse is any maltreatment of children or adolescents by their parents,
      guardians or other caretakers. Dentists must be able to recognize abused children
      and confirm the diagnosis. New York State law requires that dentists report
      suspected cases of child abuse or neglect to a local child protective agency.
      Should their suspicions be unsubstantiated, they are protected by law from
      liability.

PMID- 8139821
TI  - Desmoplastic fibroma. A rare oral tumor in children.
AB  - A report on confirmed cases of desmoplastic fibroma in a 30-month-old male and a
      nine-year-old male, both of which responded well to surgical therapy and neither
      of which has shown signs of recurrence. A 10-year clinical and radiographic
      follow-up is included.

PMID- 8139823
TI  - Success is in the flossing, not the type of dental floss.

PMID- 8139822
TI  - Novel method of treating large cysts of jaws in children.
AB  - The odontogenic keratocyst is remarkable because of its aggressive behavior and
      high recurrence rate. Managing these cysts is the clinician's primary problem. An
      innovative technique for treating children that minimizes postoperative
      complications and maximizes results is described here.

PMID- 8139824
TI  - Team spirit.

PMID- 8139825
TI  - Bilateral gustatory sweating as a sign of diabetic neuropathy.
AB  - Gustatory sweating is a relatively common sequela to parotidectomy and is almost
      always unilateral in nature. This article presents a case of bilateral gustatory
      sweating in a patient with no history of facial trauma or surgery who was
      undergoing periodontal therapy. A thorough examination determined the cause of
      diaphoresis to be autonomic neuropathy as a result of a 26-year history of Type
      II diabetes mellitus. Few cases of this rare complication of diabetes have been
      described, and the current case represents the first report in the dental
      literature.

PMID- 8139826
TI  - Major aphthous ulcers in patients with HIV disease.
AB  - Major aphthous ulcers are associated with a high degree of morbidity in patients
      infected with human immunodeficiency virus. A large representative cohort
      infected with human immunodeficiency virus was examined to evaluate the
      prevalence of major aphthous ulcers, demographic data of patients with major
      aphthous ulcers, and the usage of major aphthous ulcers as a marker for immune
      deterioration. The effects of tobacco smoking and the use of specific
      antibiotics, trimethoprim/sulfamethoxazole or dapsone, on the development of
      major aphthous ulcers was also investigated. In a population of 767 persons
      infected with human immunodeficiency virus, major aphthous ulcers were found at a
      prevalence rate of 3.1% (24 patients). This type of lesion did not show any
      predilection for human immunodeficiency virus transmission category, ethnic
      group, or gender. Persons who received trimethoprim/sulfamethoxazole or dapsone
      or had a history of tobacco smoking showed a decreased prevalence of major
      aphthous ulcers. All patients (100%) with major aphthous ulcers had CD4+ cell
      counts below 100 cells/mm3, but only 50% had a previous acquired immunodeficiency
      syndrome defining illness. Major aphthous ulcers in persons infected with human
      immunodeficiency virus are suggestive of severe immune suppression and may serve
      as a marker for human immunodeficiency virus disease progression.

PMID- 8139827
TI  - Tongue, primary amyloidosis, and multiple myeloma.
AB  - A case of macroglossia and resulting apertognathia because of primary amyloidosis
      in a 65-year-old man with multiple myeloma is described. In addition, a
      retrospective study of the oral manifestations of primary amyloidosis and
      multiple myeloma in the last 15 years is reported.

PMID- 8139828
TI  - Oral histoplasmosis in a patient infected with HIV. A case report.
AB  - Histoplasmosis is a frequent complication of HIV infection and is usually the
      result of reactivation. In the immunocompromised host, histoplasmosis may cause a
      chronic pulmonary infection or disseminated disease. In the setting of
      disseminated disease, oral lesions are present in 30% to 50% of patients and may
      occur in almost every part of the oral mucosa. The most common sites are the
      tongue, palate, and buccal mucosa. In some cases, oral lesions appear to be the
      primary or only manifestation of disease. We have been able to find only five
      case reports in the literature of histoplasmosis in HIV infection with oral
      lesions. In two of the cases, histoplasmosis was apparently localized to the oral
      cavity, whereas two cases also had evidence of disseminated disease, the fifth
      was undetermined. We report one such case of apparently localized oral
      histoplasmosis in a patient with HIV infection.

PMID- 8139829
TI  - Orofacial artefactual disease.
AB  - Self-induced lesions of the face and mouth may occasionally be encountered in
      dental practice. In general the deliberate creation of orofacial lesions is an
      indication of underlying psychiatric disease of various types that usually
      involve a personal gain by the patient from having such lesions. We present three
      cases of deliberately self-induced lesions and discuss the problem of diagnosis
      and management of these cases.

PMID- 8139830
TI  - Topical application of capsaicin for treatment of oral neuropathic pain and
      trigeminal neuralgia.
AB  - Neuropathic pain may be a major cause of pain in the head and neck. Trigeminal
      neuralgia may appear as intraoral pain. This article reviews a series of 24
      consecutive cases of oral pain treated with topical capsaicin. Complete remission
      of neuropathic pain was seen in 31.6% of patients; partial remission was achieved
      in 31.6% of patients. Trigeminal neuralgia with an intraoral trigger was less
      responsive to topical therapy than neuropathic pain. Further study is needed to
      clarify the efficacy of topical capsaicin in neuropathic and neuralgic pain and
      the effect of differing dosages and frequency of application. On the basis of the
      findings in this open-label clinical trial, controlled clinical study of
      capsaicin in neuropathic oral pain states appears warranted.

PMID- 8139831
TI  - Analysis of the oral manifestations of systemic sclerosis.
AB  - The oral signs and symptoms in 32 patients with systemic sclerosis were
      evaluated. Oral mucosal telangiectasia was present in 18 cases (56.3%) and was
      not restricted to the limited form of systemic sclerosis. The interincisal
      distance was significantly decreased in the patients with systemic sclerosis
      compared with the 17 controls (p < 0.001). The distance between the vermillion
      borders was also significantly decreased when the 14 patients with salivary
      hypofunction were compared with the 18 cases without decreased salivary secretion
      (p < 0.05). Twenty-two (69%) of the patients exhibited keratoconjunctivitis
      sicca, salivary hypofunction, or both. Lip biopsy was performed in 16 cases. Two
      cases with inflammatory signs characteristic of Sjogren's syndrome were found,
      and six patients showed the histologic signs of labial gland fibrosis. Five of
      these cases belonged to the group of limited cutaneous systemic sclerosis that
      indicates the generalized nature of the fibrotic processes even in systemic
      sclerosis with less extensive skin involvement. Of the 10 cases investigated by
      electron microscopy, all but one showed a thickening of the capillary basal
      lamina, lamellar arrangement within the basement membrane, or capillary
      endothelial vacuolization. Three of these cases belonged to the patients with
      disease onset within 2 years, showing that capillary vascular lesion is present
      in the early cases and that vascular injury affects even those tissues that do
      not seem to be evidently involved by clinical examination.

PMID- 8139832
TI  - Adult rhabdomyoma. A light microscopic, ultrastructural, virologic, and
      immunologic analysis.
AB  - Adult rhabdomyoma is a rare benign tumor of skeletal muscle origin that
      frequently arises from musculature of the head and neck region. In this study we
      report five cases of adult rhabdomyoma. Light and electron microscopic
      examination revealed the typical cellular features as described by others. The
      results of immunophenotyping and quantitation of nucleolar organizer regions were
      consistent for a benign skeletal muscle tumor. Epstein-Barr virus and human
      papillomavirus genomic DNA could not be detected by in situ hybridization.

PMID- 8139833
TI  - Multinodular versus plexiform neurilemoma of the hard palate. Report of a case.
AB  - Neurilemoma (schwannoma) is the most commonly encountered nerve sheath tumor of
      the oral cavity. It generally appears as a single encapsulated nodule that
      occasionally causes pain or discomfort. The tongue is involved most frequently,
      followed by the palate, floor of mouth, and buccal mucosa. Neurilemomas occur
      most often during the second or third decades of life. Our patient is a 21-year
      old woman with a recurrence of a palatal mass that was excised 3 years earlier.
      Histologically the lesion appeared to be a multinodular neurilemoma, a pattern
      rarely reported in the oral cavity.

PMID- 8139834
TI  - Head and neck manifestations of tumoral calcinosis.
AB  - Intraoral facial and laryngeal features of tumoral calcinosis are reviewed in six
      patients of Jewish-Yemenite descent. Extraoral features included calcified
      masses, erythematous patches, and angular cheilitis. Oral soft tissue findings
      included papillary hyperplasia of the lip vermilion and velvety-red macules on
      the tongue, palate, and buccal mucosa. Gingival findings included advanced
      periodontitis and an erythematous marginal gingivitis. In all patients,
      orthognathic evaluation revealed a concave profile, retruded maxilla, and
      relative mandibular prognathism. Although previously reported clinical dental
      abnormalities were not present, extracted teeth demonstrated abnormal dentin.
      Hoarseness was present in all patients and was the earliest appearing feature in
      two patients. The appearance of these head and neck findings preceded the
      classical manifestations of tumoral calcinosis and may be helpful in the early
      diagnosis of this entity. The varied reported features of tumoral calcinosis
      support the notion that this disease may present multiple formes frustes with
      variable clinical expressivity.

PMID- 8139835
TI  - Free and acetylated polyamines as markers of oral cavity tumors.
AB  - Differences in tissue concentrations of N1- and N8-acetylspermidine and
      cadaverine in squamous cell carcinoma of the oral cavity compared to the
      surrounding healthy tissue, as well as to epulides and other benign oral lesions
      (papillomas, lipomas, and fibromas) are assessed. The results indicate that only
      N1-acetylspermidine has use as a marker for diagnosis because its concentration
      is higher in malignant tissue. Its use in prognosis and posttreatment monitoring
      requires further exploration.

PMID- 8139836
TI  - Study of the apices of human permanent teeth with the use of a scanning electron
      microscope.
AB  - The apical region of the roots of 38 maxillary incisors, 25 mandibular incisors,
      29 maxillary second premolars, 92 mandibular first and second premolars, 12
      maxillary first molars, and 17 mandibular first molars were prepared and studied
      with the use of a scanning electron microscope. The number and size of the main
      apical foramina, their distance from the anatomic apex, and the existence and
      size of accessory foramina were recorded, summarized, and statistically analyzed.
      More than one main foramen was observed in all groups except for the palatal root
      of maxillary molars and the distal root of mandibular molars. Accessory foramina
      were also observed in all groups of teeth. The distal roots of mandibular molars
      had the largest size main foramen (mean value, 392 microns), whereas the
      maxillary premolars had the largest accessory foramina (mean value, 53.4 microns)
      and the most complicated apical morphologic makeup. The distance of the main
      foramen from the anatomic apex never exceeded 1 mm. The highest values were
      observed at the mandibular incisors (978 microns), the distal root of mandibular
      molars (818 microns), and the upper premolars (816 microns). All values showed
      satisfactory fitting to normal distribution.

PMID- 8139837
TI  - Detection of mineral loss in approximal enamel by subtraction radiography.
AB  - The purpose of the present study was to determine whether digital subtraction
      radiography will improve detectability of small, mechanically prepared defects
      within dental enamel. Lesions with an extent of 1 mm in vertical direction and
      representing 5% to 10% mineral loss in the direction of the x-ray beam were
      prepared in eight extracted molars. Radiographs of teeth with defects were
      subtracted from radiographs taken before the lesions were prepared. Seven
      observers evaluated the images using a five-point confidence rating scale
      (receiver operating characteristic technique). Examination of the original
      radiographs showed increasing accuracy of radiographic interpretation with
      increasing mineral loss as judged from the areas beneath the receiver operating
      characteristic curves. The same observation was made using subtraction images
      with and without contrast enhancement. There was no indication that subtracted
      images provided better diagnostic validity than the original radiographs. In
      conclusion, subtraction images do not seem to improve the diagnosis of well
      defined lesions within dental enamel.

PMID- 8139838
TI  - Evaluation of off-axis projection geometry in dental panoramic radiography.
AB  - New electronic imaging capabilities afforded by the use of linear charged-couple
      device arrays allow acquisition of three-dimensional information through
      simultaneous recordings from multiple sensors situated at different fixed angles.
      In theory, the resulting data can be processed to yield images tailored to
      specific diagnostic tasks that can be produced and manipulated on demand after
      exposure. The first step to determine the practical potential of such a system in
      panoramic radiography is to demonstrate the degree to which specific changes in
      projection geometry can be used to improve performance of selected diagnostic
      tasks of clinical interest in dentistry. Hence, the purpose of this investigation
      was to explore the potential to reduce proximal overlap that exist in current
      panoramic radiographs and also to displace the blurred image of the spine from
      areas of diagnostic interest through the use of off-axis projection geometry of
      the slit beam of radiation. As the off-axis angulation increased, more embrasures
      in the different areas of the dental arches of skull specimens were opened; the
      effects of beam angulation in the number of open embrasures was statistically
      significant (ANOVA, p < 0.05). A hypothetical multibeam system significantly
      improved the projection geometry toward the creation of images that contain
      little, if any, proximal overlap when compared with the conventional bilaterally
      symmetrical projection geometry system (t test, p < 0.001). At 6 degrees off-axis
      projection angle, the system was able to clear completely the anterior area from
      the superimposing shadow of the spinal column. The results show that multibeam
      alternatives to the single beam projection can significantly improve diagnostic
      quality in panoramic radiographs.

PMID- 8139839
TI  - Clinical comparison of two panoramic modalities and posterior bite-wing
      radiography in the detection of proximal dental caries.
AB  - A clinical study was designed to examine whether the Philips OrthOralix SD
      (Gendex Dental Systems, Monza, Italy) orthogonal panoramic projection could
      improve diagnostic accuracy over standard projections in the detection of
      proximal surface caries. Thirty-five sets of radiographs that demonstrated
      optimal image characteristics were selected. Using a five-point scale, 18 viewers
      evaluated whether specified lesions were present or absent. Viewer data was then
      compared with a consensus radiographic assessment of the state of the proximal
      areas. Receiver operating characteristic curves were generated with the use of a
      maximum-likelihood method of fit. The area under the receiver operating
      characteristic curve was used as the index of diagnostic accuracy. The mean
      receiver operating characteristic areas for orthogonal and standard projection
      panoramic and bite-wing radiography to detect the presence of proximal dental
      caries were 0.68 +/- 0.03, 0.69 +/- 0.03, and 0.79 +/- 0.03 respectively.
      Critical ratio analysis was used to compare the means for all possible pairings
      of imaging modalities. In overall performance, conventional bite-wing radiographs
      gave a significantly greater diagnostic yield for proximal caries than the
      Philips OrthOralix SD orthogonal or standard panoramic modalities (p > 0.05). The
      orthogonal projection did not improve diagnostic accuracy in the detection of
      proximal carious lesions compared with the standard projection.

PMID- 8139840
TI  - Comparison of stent versus laser- and cephalostat-aligned periapical film
      positioning techniques for use in digital subtraction radiography.
AB  - Digital subtraction radiography is a sensitive diagnostic technique that allows
      detection of subtle calcific changes in the jaws and teeth that would otherwise
      not be radiographically visible. However, a high failure rate associated with
      stent-based periapical film-positioning strategies combined with the complexity,
      expense, and time of image acquisition has limited the clinical utility of this
      technique. This study compares a new technique that uses film-positioning
      instruments, laser alignment beams, and a cephalostat with a previously validated
      method that used film positioners and elastic impression material. Two series of
      periapical radiographs were taken of six different anatomic areas of six phantoms
      using both techniques. Film pairs were digitally subtracted twice and analyzed. A
      paired t test for difference in standard deviation of mean pixel values revealed
      no difference in repositioning accuracy between the two techniques (p = .68). The
      new technique eliminates problems that are associated with the use of elastomeric
      impression materials.

PMID- 8139841
TI  - [Nd. Yag treatment of bladder tumors].
AB  - Between 1989 and 1992 116 patients suffering from tumours of the bladder were
      treated with Nd. Yag laser. In 74 cases only laser treatment was applied, in 42
      cases the laser treatment was combined with transurethral resection (TUR). The
      patients were in the phases TA, T1, T2 and in the majority of them the
      histological examination did not reveal grade 3. No considerable complications,
      e. g. perforation of the bladder or important haemorrhages were observed during
      laser treatment. After laser and TUR + laser treatment, respectively, relapses
      occurred in 16-19% of the cases, considerably less than after treatment carried
      out with TUR exclusively.

PMID- 8139842
TI  - [Gene deletion analysis in molecular diagnosis of Duchenne-Becker muscular
      dystrophy].
AB  - Deletion analysis of the dystrophin gene (Xp21) was carried out by examinations
      of the most frequently deleted 18 exons (3., 4., 6., 8., 12., 13., 17., 19., 43.,
      44., 45., 47., 48., 49., 50., 51., 52. and 60. exon) and the muscle specific
      promoter in 42 Duchenne and Becker muscular dystrophy (DMD/BMD) affected patients
      with multiple polymerase chain reaction (PCR). 22 (52%) of 42 patients were found
      to have one or more exon deletions. 9% BMD patients (milder allelic form) were
      found in the deletion group versus 35% in the non deletion group. This method
      seems to be useful for prenatal genetic diagnosis in the family of deletion
      patients.

PMID- 8139843
TI  - [Prophylactic and therapeutic use of immunoglobulins in patients with bone marrow
      transplantation].
AB  - Eleven children were transplanted in our BMT Unit. All but one received standard
      IVIG preparations in doses of 100 mg/kg b. w. regularly on days before and after
      transplantation -1, +14, +28, +60 and +90, respectively, and anti-CMV hyperimmune
      globulin (Cytotect) was given to six patients in the same doses, respectively. In
      spite of the severe immunodeficiency bacterial infections were verified only in
      four patients, and CMV infection in three. New infection only occurred in two of
      the three patients, who hadn't been given CMV prophylaxis, while in the group of
      six children having been given Cytotect prophylaxis only one became infected from
      endogenous reactivation of CMV. Therapeutic application of immunoglobulin
      compounds were used in four of our transplanted patients. Two of them suffered
      from sepsis during transplantation, one from protracted immunoneutropenia and one
      from CMV antigenaemia after the transplantation, respectively. Our conclusion is
      that the administration of immunoglobulins may contribute to the prevention of
      infections and to the treatment of some complications in BMT recipients. Anti-CMV
      immune globulin seems to be more effective than standard IVIG in the prevention
      of CMV infection.

PMID- 8139844
TI  - [Leptospirosis in Pomurje and Slovenia].
AB  - In Pomurje leptospirosis is endemic. During the years 1964-1985 there were 407
      leptospiral cases reported in Slovenia, 366 of which were in Pomurje. Inclusion
      in this study required indication of leptospirae with a fourfold increase of the
      titer of antibodies or the isolation of leptospirae from hemocultures. In Pomurje
      in this period 214 men (58.47%) and 152 women (41.53%) were infected. The average
      morbidity rate was 12.75/100,000 inhabitants. The highest rate was in the country
      of Lendava (23.14/100,000). Ten serotypes were confirmed: grippotyphosa in 122
      (33.33%) of the patients, sejroe in 91 (24.86%), icterohaemorrhagie in 50
      (13.66%), saxkoebing in 48 (13.11%), australis in 47 (12.84%), canicola and
      pomona in two cases, tarassovi and autumnalis in one patient. In one case, the
      serotype could not be differentiated. The disease occurs throughout the years. In
      contrast to Western Europe in Pomurje there exists a much larger percent of
      infected women and a high percentage among the elderly. Two patients have died
      (mortality rate is 0.55%). One of them succumbed on the 5th day of infection due
      to massive bleeding in the heart and other organs. The other died on the 12th day
      under the influence of a severe Weil's syndrome.

PMID- 8139845
TI  - [A case of successful pregnancy in a woman with anti-phospholipid syndrome and
      habitual abortion].
AB  - A case of a successful pregnancy is presented in a woman with anti-phospholipid
      syndrome and habitual abortions. She was treated with heparin-salicyl therapy
      during her pregnancy. No complications were noted. The significance of the
      presence of anti-phospholipid antibodies is stressed. The other therapeutic
      possibilities are discussed.

PMID- 8139846
TI  - [National Stafania Society (1915-1941)].

PMID- 8139847
TI  - [Laennec and Skoda, classical figures in the field of diagnostics in internal
      medicine].

PMID- 8139848
TI  - [Emergency and elective percutaneous recanalization in ischemic heart disease].
AB  - The success and complication rates of programmed angioplasty performed after
      diagnostic coronarography and of ad hoc angioplasty performed at the time of the
      diagnostic catheterization are analysed in the study. We have attempted
      percutaneous recanalisation of 1071 lesions on 440 patients and dilated an
      average 2.4 stenoses or occlusions by patient. Immediate intervention was
      performed on 59.5% of patients with overall 91.7% success rate. The need for
      emergency surgery was 0.7%, periprocedural myocardial infarction was observed in
      1.5%, and the mortality rate was 1.5%. The success and complication rates were
      similar for both studied groups. In the ad hoc angioplasty group there were
      relatively more easily solvable cases concerning the techniques, however the
      incidence of unstable angina and acute, emergency settings were more frequent. Ad
      hoc angioplasty does not diminish the success rate and resulted a faster, and
      more spectacular recovery in the above severe cases. Extensive experience with ad
      hoc angioplasty has proven it to be reasonable approach, efficient and safe
      variation not only in rescue, but also in complex angiological settings, if the
      considerable logistics are possible in an individual cardiovascular center. The
      provision of ischaemic heart disease patients is subject to the planning and
      creating such anti-ischaemic interventional cardiological centers in Hungary.

PMID- 8139849
TI  - [Familial ovarian cancer syndrome].
AB  - This paper gives an overview of the familial ovarian cancer. Ovarian cancer prone
      families defined as two or more first or second degree relatives with ovarian
      cancer, are of clinical importance because first or second degree family members
      of affected women are at risk of developing ovarian cancer. These women need
      surveillance including prophylactic oophorectomy in those with increased risk.
      Women with hereditary ovarian cancer are at the greatest risk. Familial ovarian
      cancer studies are also important in terms of research. They provide the best
      hope of identifying a gene involved in the genesis of ovarian cancer. There is
      good evidence that such a gene is likely to be involved in the development of non
      familial ovarian cancer as well. This might be a clue to understanding the
      biology of ovarian cancer. Therefore ovarian cancer prone families should be
      identified and, since familial ovarian cancer is rare, available details about
      affected and non-affected family members should be registered at least at
      national level. The author set up the Hungarian Registry for familial ovarian
      carcinoma at the National Institute of Oncology Budapest.

PMID- 8139850
TI  - [Comparative studies in the diagnosis of Chlamydia trachomatis infections].
AB  - Comparative evaluation of different methods for diagnosis of chlamydial
      infections was carried out. During the culture of the bacteria cycloheximide
      treated McCoy cell line was used, and elementary and reticulate bodies were
      detected by monoclonal antibodies with immunofluorescent (IF) method. Chlamydia
      specific IgM and IgG antibodies were determined with ELISA using S. minnesota mR
      595 lipopolysaccharide (LPS) as antigen and by indirect IF with C. trachomatis L2
      antigen. According to the results the LPS-ELISA developed in their laboratory
      proved to be an applicable method for the serodiagnosis of chlamydial infections
      parallel with the culture method.

PMID- 8139851
TI  - [The effect of lesser curve seromyotomy of the stomach in animal experiments].
AB  - The authors investigated the efficiency of the seromyotomy of the lesser
      curvature of the stomach in 11 dogs. Reduction of the acid production was
      verified by glass electrode pH measuring of the gastric mucosa. Scintigraphic
      examination showed that the operation did not damage the motor function
      (motility) of the stomach. The fact of peripheral vagotomy was established by
      histological examination: degeneration of nerve fibres was detected on the
      peripheral side of the line of the seromyotomy, vacuolar degeneration was found
      in the cells of parasympathetic ganglions, and amputation neurinomas were shown
      in the line of the seromyotomy.

PMID- 8139852
TI  - [Carnitine-deficient cardiomyopathy].
AB  - The case of a 10 month old girl with carnitine deficiency caused neuromuscular
      symptoms and cardiomyopathy is reported. After oral carnitine therapy dramatic
      improvement in neurological status and in cardiac function was confirmed. This
      case is the first infant our country with dilated cardiomyopathy successfully
      treated by oral L-carnitine.

PMID- 8139853
TI  - [Jozsef Antall, medical historian (1932-1993)].

PMID- 8139854
TI  - [Our reputation abroad and at home--thoughts while re-reading Gammopathy, by
      Janos Jako].

PMID- 8139855
TI  - [Incidence of T3-hyperthyroidism].

PMID- 8139856
TI  - [Nursing at daybreak. Position of German nursing personnel on the start of the
      morning shift at 6:00 a.m].

PMID- 8139858
TI  - [Healthy nutrition--already in nursery school].

PMID- 8139857
TI  - [Health consciousness--and AIDS].

PMID- 8139859
TI  - [Playfully through nursing school with the health caravan by Big-Tours].

PMID- 8139860
TI  - [I chose the profession because I wanted to care].

PMID- 8139861
TI  - [Health counseling in nursing: shown by discussing incontinence].

PMID- 8139862
TI  - [A hot iron: the independence of nursing].

PMID- 8139864
TI  - [Anteroom to the operating room--a vacuum or a place for humanism?].

PMID- 8139863
TI  - [The European Economic Community].

PMID- 8139865
TI  - [Operating room nursing--reality or vision?].

PMID- 8139866
TI  - [First experiences with the defibrillator check list].

PMID- 8139867
TI  - [Is dignified treatment possible in the operating room?].

PMID- 8139868
TI  - [Reform in nursing education has been a reality in Israel for a long time].

PMID- 8139869
TI  - [Hospital legislation: news in nursing].

PMID- 8139870
TI  - New immunization practices and prophecies.

PMID- 8139871
TI  - Vaccine prevention of group B streptococcal disease.

PMID- 8139872
TI  - Respiratory syncytial virus vaccines: can we improve on nature?
AB  - Both inactivated and live RSV candidate vaccines will continue to be tested in
      infants and young children. Sequential vaccination, with a first dose of live
      attenuated vaccine followed by boosting with intramuscular subunit vaccines, also
      is an option. We are encouraged by the fact that influenza subunit and cold
      adapted live vaccines are both safe and immunogenic in infants and children of
      the same age group. Testing of RSV vaccines must proceed at a slower pace because
      of the phenomenon of vaccine-induced enhanced disease. Curiously, this phenomenon
      of disease enhancement has not been demonstrated in the case of inactivated
      influenza or parainfluenza virus vaccines. Another important step in the
      development of RSV vaccines is to determine a target population. Clearly,
      children with underlying cardiac or pulmonary disease would benefit from an RSV
      vaccine. It can be expected that 1% of all infants in the general population will
      be hospitalized for RSV infection during their first year of life. These infants
      also would appear to be good candidates for an RSV vaccine, but it is unclear how
      they would be identified before infection occurs. Immunization of the entire
      population of infants to protect these 1% would be feasible only if the vaccine
      were inexpensive and easily administered.

PMID- 8139873
TI  - Vaccines to prevent bacterial enteric infections in children.
AB  - Considerable progress has been made in the last decade in developing vaccines
      against the most important bacterial enteric infections. Two new vaccines against
      typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in
      many countries. Newer generations of more sophisticated typhoid vaccines are
      undergoing clinical testing including recombinant attenuated S typhi strains and
      Vi polysaccharide-carrier protein conjugate vaccines. Two inactivated oral
      cholera vaccines, consisting of inactivated V cholerae 01 bacteria alone or in
      combination with the B subunit of cholera toxin, each conferred 50% to 53%
      protection over 3 years in a field trial in Bangladesh where subjects were
      immunized with a three-dose regimen. An engineered live oral cholera vaccine,
      strain CVD 103-HgR, has been shown in extensive clinical trials to be well
      tolerated by children and adults in developing countries and highly immunogenic
      following administration of just a single oral dose; a large-scale field trial of
      the efficacy of this vaccine is underway. Several candidate vaccines against
      Shigella and enterotoxigenic E coli are in clinical trials.

PMID- 8139874
TI  - Prospects for vaccination against herpes simplex virus.

PMID- 8139875
TI  - Prospects for childhood immunization in the next decade.
AB  - Prospects for vaccine research, development, and use over the next decade are
      extraordinarily optimistic. Innovative investigative programs promise new
      vaccines with reduced numbers of injections, combinations of multiple antigens,
      and confinement of administration to the early weeks or months of life. Enhanced
      attention to the infrastructure and support of immunization programs should
      rapidly augment coverage to more than 90% of the US infant population in the
      first 2 years of life with all the recommended vaccines. Programs of the WHO and
      CVI should extend protection from morbidity and mortality of diseases preventable
      with vaccine to children of all nations. Adjustments and realignments of the
      Vaccine Injury Compensation Program should reduce to realistic dimensions the
      finances of benefits for children who suffer the rare, true adverse responses to
      required immunizations. In order to maintain familiarity and leadership in
      childhood immunization, pediatricians will need to maintain careful attention to
      and familiarity with all these emerging developments.

PMID- 8139876
TI  - Diagnosis and management of croup and epiglottitis.
AB  - Viral croup and epiglottitis are two major inflammatory causes of airway
      obstruction in children. Two conditions, spasmodic croup and membranous
      laryngotracheobronchitis, are also frequent causes of obstruction on an
      inflammatory basis. Rapid diagnosis and effective management are required to
      ensure an uncomplicated outcome. The pharmacologic treatment, role and timing of
      endoscopy, and airway management principles are discussed.

PMID- 8139877
TI  - Pathophysiology and treatment of bronchopulmonary dysplasia. Current issues.
AB  - Although much has been learned about BPD in the 25 years since its initial
      description, BPD remains a significant complication of prematurity. Substantial
      advances into the understanding of its pathophysiology and pathogenesis have been
      made and are reflected in new therapeutic interventions. Much current research is
      directed towards the role of prevention, exploring new approaches for
      accelerating lung maturation with combined maternal steroid and thyrotropin
      releasing hormone (TRH) therapy, surfactant replacement therapy, high frequency
      oscillatory ventilation, antioxidant administration, manipulation of endogenous
      antioxidants, and other pharmacologic strategies to minimize lung injury. The
      impact of other technologies, such as synchronized intermittent mandatory
      ventilation, perfluorocarbon (liquid) ventilation, and perhaps inhaled nitric
      oxide therapy may become additional parts of the clinical regimen for some cases
      of severe neonatal respiratory failure. Less information is available on
      mechanisms which can hasten lung healing. Ongoing studies of inflammatory
      products, growth factors, and cytokines may lead to new therapies which will
      favorably influence the fibroproliferative phase of disease. In the meantime, the
      medical and social impact of BPD continues to remain a significant problem not
      only during infancy but also throughout life. Mildred Stahlman, MD, recently
      wrote that (a)s sanguine as the future looks for surfactant therapy, it may leave
      us with more very low-birth weight infants who survive, whose potential for
      normal pulmonary growth and development is unknown, and whose very immature organ
      systems, besides the lung, are still susceptible to metabolic, neurologic, and
      other problems. As more survivors are reaching young adulthood, respiratory and
      neurodevelopmental complications persist. Thus, as advances in the care of the
      premature newborn with respiratory distress have dramatically improved survival,
      the management of chronic lung disease and related problems remains a continuing
      challenge.

PMID- 8139878
TI  - Smoke inhalation injury.
AB  - Smoke inhalation injury in children still represents a significant cause of
      pulmonary disease and mortality. Carbon monoxide and other toxic products of
      combustion are major determinants of severity. Early hypoxemia is a contributor
      to over 50% of deaths. There are several clinical entities: upper airway
      obstruction, bronchospasm, consolidation, pulmonary edema, ARDS, and late
      pneumonia. Intensive care has improved outcome from burns, but pulmonary injury
      is still an important cause of mortality. New therapies such as high frequency
      ventilation may improve the outcome. Primary prevention is the most important way
      to reduce the poor outcome from significant exposure.

PMID- 8139879
TI  - Adult respiratory distress syndrome in children.
AB  - In spite of modern technological advances, ARDS continues to be an important
      cause of morbidity and mortality from a diverse group of disorders such as
      sepsis, trauma, and aspiration. ARDS represents a target organ injury resulting
      from activation of the host's inflammatory cells and uncontrolled liberation of
      inflammatory mediators. In most instances, therefore, ARDS is a localized
      manifestation of a widespread onslaught characteristic of SIRS. At this time,
      there are no proven interventions to prevent ARDS, and the management is mainly
      supportive. Modulation of the host's inflammatory response seems to hold the most
      promise for prevention and treatment of ARDS. Such strategies need to be explored
      with well-controlled clinical trials.

PMID- 8139880
TI  - Extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation has now evolved into standard therapy for
      patients unresponsive to conventional ventilatory and pharmacological support.
      This article presents a clinical review of extracorporeal life support and its
      application to neonatal and pediatric patients as well as children requiring
      circulatory support after open heart surgery.

PMID- 8139881
TI  - Update on pediatric flexible bronchoscopy.
AB  - Technological advances in flexible bronchoscopy have expanded the clinician's
      ability to diagnose and treat pulmonary disease in children. During the neonatal
      period, flexible bronchoscopy has contributed to the understanding of the
      incidence and factors responsible for acquired airway lesions. The ability to
      selectively collect lower airway secretions has contributed to the care of
      immunocompromised patients with new pulmonary infiltrates. New therapies may use
      the flexible bronchoscope to specifically target lower airway tissues of
      interest. Because of the breadth of both current and future applications, most
      pediatricians will require a working familiarity with the benefits of flexible
      bronchoscopy in their patients.

PMID- 8139882
TI  - Pulmonary function in infants and children.
AB  - The assessment of pulmonary function in infants and children with lung disease
      can add substantially to their diagnosis and management. This article is a
      practical review of techniques such as peak flow measurement and spirometry which
      can be performed in the home or office setting. More complex methods such as
      airway challenge and infant lung function testing techniques also are discussed.

PMID- 8139883
TI  - A surgeon's valedictory.

PMID- 8139884
TI  - Effects of iodides on inflammatory processes.

PMID- 8139885
TI  - Irvine H. Page: a man for all reasons.

PMID- 8139886
TI  - Dismissed observations: the kindling effect, a case study.

PMID- 8139888
TI  - Are you an obsolete M.D.? Some clues to self-recognition.

PMID- 8139887
TI  - Data on animal experimentation in the United States: what they do and do not
      show.

PMID- 8139889
TI  - From aphorisms to APACHE: medicine's brave new world.

PMID- 8139890
TI  - Natural history of disease and placebo effect.

PMID- 8139891
TI  - Did Mozart have Tourette's syndrome? Some comments on Mozart's language.

PMID- 8139892
TI  - Neurosis: a Ms-diagnosis.

PMID- 8139893
TI  - An evolutionary approach to pain.

PMID- 8139894
TI  - An explanation of high death rates among New World peoples when in contact with
      Old World diseases.

PMID- 8139895
TI  - NJSNA position statement on provision of care for persons infected with HIV
      infection/AIDS.

PMID- 8139896
TI  - NJSNA position statement on animal research.

PMID- 8139897
TI  - HIV and hepatitis B testing.

PMID- 8139898
TI  - [Backache--the bane of the welfare state?].

PMID- 8139899
TI  - [Sciatica and herniated disk. Current aspects of pathophysiology and pain
      mechanisms].
AB  - Pathoanatomical and pathophysiological aspects of spinal nerve roots involved in
      disk herniation are discussed, and recent advances in our understanding of nerve
      root physiology and pathophysiology summarised. Evidence is presented suggesting
      that nerve roots may be affected not only by mechanical compression but also by
      nucleus pulposus tissue via biochemical mechanisms. Clinical symptoms are also
      discussed, as are recent findings regarding the diagnosis and treatment of disk
      herniation and sciatica.

PMID- 8139900
TI  - [Spinal stenosis and instability of the lumbar spine. Current aspects of
      pathophysiology and pain mechanisms].
AB  - The pathophysiology of spinal stenosis and segmental instability is discussed.
      The critical magnitude of the cross-sectional area of the cauda equina in the
      lower part of the vertebral canal is related to the dynamic loading of the spine,
      nerve impulse conduction and nerve root nutrition. Present knowledge of segmental
      instability is discussed, and an account is given of findings obtained during
      dynamic measurements with an intervertebral motion device (IMD), which indicate
      pathological motion patterns to differ from one pair of vertebrae to another.

PMID- 8139901
TI  - [Target for anti-ulcer agents--pH, H. pylori or NO?].
AB  - Although until recently the reduction of gastric acid secretion was the primary
      aim in the treatment of peptic ulcer disease, it is now recognised that the
      presence of Helicobacter pylori and not only acid is required to produce duodenal
      ulcer. Accordingly, the part played by gastric acid has been relegated to the
      contributor to the effects of H pylori infection. Recent research into the
      pathogenesis and treatment of peptic ulcer disease suggests the locus of
      receptors for acid stimulants, such as acetylcholine, histamine and gastrin, to
      be the immune cell in the lamina propria of gastric mucosa, and not the parietal
      cell. Thus the effects of acid stimulants, as well as those of mediators of other
      gastro-intestinal functions, such as oesophageal and gastroduodenal bicarbonate
      secretion, may be directly transmitted to the effector cells via macrophages and
      plasma cells. Nitric oxide (NO) may be the agent mediating the interaction
      between immune and epithelial cells. If these findings are validated and
      confirmed in man, they may pave the way for new approaches to the treatment of
      acid-related disorders, resulting in therapeutic strategies that do not
      necessitate the eradication of H pylori.

PMID- 8139902
TI  - [Pulmonary syndrome caused by Hantavirus--a new syndrome with high mortality].
AB  - An outbreak of a previously unknown, severe infectious disease with rapidly fatal
      respiratory distress was reported from Southwestern USA in May 1993. The case
      fatality rate was about 60 per cent. Using PCR hantavirus RNA could be
      demonstrated in lungs and other tissues from patients. Mice and others rodents, e
      g Peromyscus maniculatus, were shown to be a reservoir of the virus. This new
      virus, designated Four Corner virus, has been further characterised and seems to
      be closely related to Puumala virus that causes nephropathia epidemica
      (hemorrhagic fever with renal syndrome) in Scandinavia and Central Europe.

PMID- 8139903
TI  - [Misconduct in medical research. A questionnaire survey among project leaders in
      health region 4].
AB  - During the period 1986-92, a questionnaire survey was conducted among research
      project administrators whose study protocols were assessed by the ethical
      committee for biomedical research in Health region 4 (Central Norway). The
      questions referred to the scientists' attitudes towards medical research ethics
      in general, and their views on the work of the committee. They were also asked to
      comment on seven statements about scientific fraud and misconduct. This paper
      presents data on misconduct from the 119 scientists who completed the
      questionnaire, i.e. 70 percent of the 159 recipients. Some 40 percent claimed
      that scientific fraud is a problem in Norway, but 46 percent maintained that it
      is less so than in other countries. More than every fourth researcher (27
      percent) knew of one or more cases of scientific misconduct, 42 percent stated
      that their knowledge was not publicly known, 18 percent felt that they had been
      exposed to misconduct themselves. A majority (60 percent) stated that a better
      system is needed to investigate claims of scientific fraud. The authors discuss
      these findings in relation to the personal characteristics and scientific
      qualifications of the researchers, and the current knowledge about the extent of
      scientific fraud in medicine.

PMID- 8139904
TI  - [Povl Riis--a Scandinavian forerunner in medical ethics and publishing. Interview
      by Eva Oldinger].

PMID- 8139905
TI  - [Fundamental errors in observed researches].

PMID- 8139906
TI  - [Prehospital treatment at large outdoor music festivals. Economic aspects].
AB  - An emergency facility was provided at the Midtfyn Rock Music Festival in 1990
      (comprising 7,000 musicians and ancillaries and an overall public attendance of
      60,000). A total of 329 patients were treated at the facility during the four and
      a half days that the festival lasted. The numbers of diseases and injuries were
      recorded, and the economic aspects are discussed in the article. In 74 per cent
      of cases, treatment was completed at the emergency facility, and the patients
      could be discharged. In terms of staff costs and the saving in patient transport
      costs alone, the economic gain to the community was estimated to be about 25,000
      DKR. Thus, the provision of an emergency facility was cost-effective, and is
      recommended at such mass outdoor gatherings as cultural and sports events.

PMID- 8139907
TI  - [Postgraduate education in medical sciences in Estonia].

PMID- 8139908
TI  - Incorporation of (R)- and (S)-3',4'-seco-thymidine into oligodeoxynucleotides:
      hybridization properties and enzymatic stability.
AB  - Novel flexible oligodeoxynucleotide analogues containing (R)- and (S)-3',4'-seco
      thymidine were synthesized on an automated DNA-synthesizer using the
      phosphoramidite approach. Oligodeoxynucleotide analogues (17-mers) having one or
      three modifications in the middle or one or two modifications in the ends were
      evaluated with respect to hybridization properties and enzymatic stability. 3'
      End-modified oligomers were stable towards 3'-exonuclease degradation and
      displayed acceptable hybridization properties.

PMID- 8139909
TI  - The DNA binding domains of the varicella-zoster virus gene 62 and herpes simplex
      virus type 1 ICP4 transactivator proteins heterodimerize and bind to DNA.
AB  - The product of varicella-zoster virus gene 62 (VZV 140k) is the functional
      counterpart of the major transcriptional regulatory protein of herpes simplex
      virus type 1 (HSV-1), ICP4. We have found that the purified bacterially expressed
      DNA binding domain of VZV 140k (residues 417-647) is a stable dimer in solution.
      As demonstrated by the appearance of a novel protein--DNA complex of intermediate
      mobility in gel retardation assays, following in vitro co-translation of a pair
      of differently sized VZV 140k DNA binding domain peptides, the 140k DNA binding
      domain peptide binds to DNA as a dimer. In addition, the DNA binding domain
      peptide of HSV-1 ICP4 readily heterodimerizes with the VZV 140k peptide on co
      translation, indicating that HSV-1 ICP4 and VZV 140k possess very similar
      dimerization interfaces. It appears that only one fully wild type subunit of the
      dimer is sufficient to mediate sequence specific DNA recognition in certain
      circumstances. Co-immunoprecipitation analysis of mutant DNA binding domain
      peptides, co-translated with an epitope-tagged ICP4 DNA binding domain, shows
      that the sequence requirements for dimerization are lower than those necessary
      for DNA binding.

PMID- 8139910
TI  - The conserved 7SK snRNA gene localizes to human chromosome 6 by homolog exclusion
      probing of somatic cell hybrid RNA.
AB  - Many small RNAs contribute essential activities to eukaryotic cells. In mammalian
      genomes dispersed repetitive sequences which exhibit homology to small RNAs often
      exist as pseudogenes which can complicate identification, localization, and
      analysis of the authentic gene. We mapped a productive human 7SK small nuclear
      RNA gene to human chromosome 6 by analyzing Northern blots derived from a panel
      of somatic cell hybrids that contain single human chromosomes. In order to avoid
      crossreactivity of the probe with rodent 7SK RNA, which is 98% identical to human
      7SK, a method termed homolog exclusion probing was developed. This method uses an
      excess of non-labelled rodent-specific oligodeoxynucleotide to block the rodent
      7SK RNA from hybridizing with the human-specific oligodeoxynucleotide probe. The
      effectiveness of this method to enhance the human 7SK RNA signal is demonstrated.
      The potential to map and subsequently isolate other small RNA genes by this
      approach and the use of homolog exclusion probing to discriminate among family
      members of highly related RNAs and DNAs in a single species is discussed.

PMID- 8139911
TI  - Homo- and heterodimers of the retinoid X receptor (RXR) activated transcription
      in yeast.
AB  - The polymorphic nature of sequences which act as retinoic acid response elements
      (RAREs and RXREs) in transactivation assays in mammalian cells, suggests that
      elements consisting of a direct repetition of a half site motif, separated by 1
      to 5 base pairs (DR1 to DR5), are targets for retinoic acid (RA) signalling. In a
      previous report we showed that in yeast cells, heterodimers of the retinoic acid
      receptors RAR alpha and RXR alpha were required for efficient transcription of a
      reporter gene containing a DR5 element [Heery et al., (1993); Proc. Natl. Acad.
      Sci. USA, 90: 4281-4285]. Here we report that DR1 to DR5 elements containing a
      direct repeat of the 5'-AGGTCA-3' motif, and an inverted repeat of the same
      sequence with no spacer (IR0), behave as RAREs in yeast cells coexpressing RAR
      alpha and RXR alpha, albeit with different efficacies. Heterodimer activity was
      strongest on a DR5 reporter gene, and the strength of activation of the reporter
      series (DR5 > DR1 > DR3 > DR2 = IR0 = DR4) correlated with the ability of the
      heterodimer to bind to the corresponding sequences in vitro. Significantly, a
      reporter containing a DR1 element was selectively and efficiently activated in
      yeast cells expressing only RXR alpha. This activity was dependent on the
      induction by 9-cis retinoic acid of an activation function (AF-2) located in the
      RXR alpha ligand binding domain. In addition, a strong synergistic activity of
      RXR alpha was observed on a reporter containing the putative RXR element (RXRE)
      from the rat CRBPII gene promoter. Thus, RXR alpha can function independently as
      a transcription factor, in the absence of RARs or other heteromeric partners.
      Similarly, homodimers of RAR alpha selectively stimulated the transcription of a
      DR5 reporter in a ligand-dependent manner, but less efficiently than RAR
      alpha/RXR alpha heterodimers.

PMID- 8139912
TI  - U17XS8, a small nucleolar RNA with a 12 nt complementarity to 18S rRNA and coded
      by a sequence repeated in the six introns of Xenopus laevis ribosomal protein S8
      gene.
AB  - U17XS8 RNA is a 220 nt small RNA coded by a sequence repeated in each of the six
      introns of the gene for ribosomal protein S8 of Xenopus laevis. It is mainly
      localized in the nucleolus, as shown by in situ hybridization, and it is
      assembled in a ribonucleoprotein particle (RNP) sedimenting at about 12S,
      slightly faster than U3 RNP, and with a density of 1.45 g/ml. DNA and RNA
      microinjections in Xenopus oocytes have shown that U17XS8 RNA is not the product
      of an independent transcription unit, but is produced by processing of intron
      sequences of r-protein S8 transcript, as has been recently shown for other small
      nucleolar RNAs encoded in the introns of other genes. Its accumulation during
      Xenopus development, oogenesis and embryogenesis, increases in parallel to that
      of r-protein S8 mRNA. Another interesting feature is the presence in the U17XS8
      RNA of a 12 nt sequence complementary to 18S rRNA. The results presented suggest
      a possible role of this RNA in some step(s) of ribosome assembling in the
      nucleolus. Some relevant differences between Xenopus U17XS8 RNA and the
      corresponding human U17 RNA, recently described, have been observed.

PMID- 8139913
TI  - Adenovirus DNA binding protein: helix destabilising properties.
AB  - Adenovirus DNA binding protein is a multifunctional protein essential for viral
      DNA replication. To investigate the role of the DNA binding protein in this
      process its interaction with partial DNA duplexes was examined. Duplex regions of
      DNA, created when a short DNA strand is annealed to its complementary sequence
      present in the single stranded form of M13 phage DNA, were efficiently unwound by
      DNA binding protein in a reaction that required neither ATP nor MgCl2. The
      unwinding activity of DNA binding protein was reduced by conditions which
      increased the stability of DNA duplexes. DNA unwinding by DNA binding protein was
      highly co-operative and required the single stranded DNA to be completely coated
      with the protein. Completely double stranded DNA could also be unwound by DNA
      binding protein but this reaction was sensitive to the G+C content of the DNA and
      could only be observed with relatively short DNA duplexes up to 45 base pairs in
      length. When these short double stranded DNA molecules contained binding sites
      for the transcription factors NFI and NFIII addition of the cognate factor
      blocked DNA binding protein mediated unwinding of the particular DNA duplex.
      Cleavage of DNA binding protein with chymotrypsin and isolation of the 39,000
      molecular weight C-terminal fragment indicated that the unwinding activity was
      located in this domain of the protein. In support of this contention a monoclonal
      antibody, which had previously been mapped to this region, specifically inhibited
      the DNA unwinding activity. These activities of DNA binding protein are likely to
      be involved in DNA replication, where the destabilisation of DNA duplexes could
      be important both during initiation and elongation.

PMID- 8139914
TI  - The expression pattern of Id4, a novel dominant negative helix-loop-helix
      protein, is distinct from Id1, Id2 and Id3.
AB  - Molecular interaction between transcription factors containing an basic-helix
      loop-helix (bHLH) domain is known to regulate differentiation in several cellular
      systems including myogenesis, neurogenesis and haematopoiesis. DNA-binding
      activity of the bHLH proteins is mediated via the basic region and is dependent
      upon formation of homo- and/or heterodimers of these transcription factors.
      Dominant negative (dn) HLH proteins (Id1, Id2, Id3 and emc) also contain the HLH
      dimerization domain but lack the DNA-binding basic region. Formation of
      heterodimers between dnHLH and bHLH proteins abolishes the DNA-binding activity
      of the latter. Concordantly, it was shown that the dnHLH protein Id1 inhibits
      differentiation of muscle and myeloid cells in vitro. Therefore, it was
      postulated that dnHLH proteins serve as general antagonists of cell
      differentiation. We have isolated and characterized a novel mouse dnHLH gene,
      designated Id4. The Id4 protein contains a HLH domain highly conserved among the
      dnHLH proteins from mouse and drosophila. Outside of the HLH domain, three
      additional short regions of the dnHLH proteins show some degree of homology. DNA
      binding of E47 homo- as well as E47/MyoD heterodimers is inhibited by Id4.
      Transcription of the Id4 gene results in three RNA molecules of 3.7, 2.0 and 1.7
      kb which are presumably a result of differential splicing and/or alternatively
      used polyadenylation sites within the 3' untranslated region. During
      embryogenesis, Id4 expression is up-regulated between day 9.5 and 13.5 of
      gestation. The highest expression in adult tissues was detected in testis, brain
      and kidney. Comparison of the expression patterns of the four mouse dnHLH genes
      revealed that Id4 expression differs from the more restricted expression of Id2
      as well as from the widespread expression of Id1 and Id3.

PMID- 8139915
TI  - The 5' flanking region of the rat LAP (C/EBP beta) gene can direct high-level,
      position-independent, copy number-dependent expression in multiple tissues in
      transgenic mice.
AB  - The efficiency and tissue-specificity of transgene expression in animals is
      usually subject to the position of integration into the host chromatin. We have
      discovered that a 2.8kbp fragment flanking the rat gene encoding the
      transcription factor LAP (C/EBP beta) directs position-independent, copy number
      dependent expression in transgenic-mouse livers. Concomitantly, the DNAse I
      hypersensitivity pattern normally observed in the liver is established in the
      integrated transgene construct demonstrating that this region is capable of
      creating chromatin structures equivalent to the endogenous situation. These
      observations are reminiscent of the locus control regions (LCR) described for
      several genes. Additionally, this LAP element functions with both intron-less and
      intron-containing genes. The tissue specificity of this element, however, is not
      restricted to liver. The 2.8kbp region is capable of allowing position
      independent, copy number-dependent expression in brain, kidney, heart, spleen,
      and lung, but in a construct-dependent manner. This is, to our knowledge, the
      first transcription factor gene with which a cis-linked LCR-like element has been
      associated.

PMID- 8139916
TI  - Functional difference between the two oppositely oriented priming signals
      essential for the initiation of the broad host-range plasmid RSF1010 DNA
      replication.
AB  - The broad host-range plasmid RSF1010 contains two oppositely oriented priming
      signals, ssiA and ssiB, for DNA synthesis dependent on the origin of vegetative
      DNA replication (oriV). If either ssiA or ssiB was deleted or inverted, the
      RSF1010 miniplasmids containing engineered oriVs were maintained at low copy
      numbers, replicated abnormally as dimers, and accumulated specific single strands
      in the Escherichia coli strain supplying the three RSF1010-encoded RepA, RepB',
      and RepC proteins. Interestingly, an additional intracellular supply of the Sog
      primase (the sog gene product of plasmid CoIIb-P9) reversed the replication
      deficiency of these miniplasmids with respect to all three aspects described
      above. These were also true for the RSF1010 miniplasmids in which either ssiA or
      ssiB was replaced by the primosome assembly site (PAS) or by the G4-type ssi
      signal (G site). Furthermore, comparative analysis of the functional contribution
      of the two oppositely oriented ssi signals to the DNA replication of RSF1010
      showed that, irrespective of their types, ssi signals conducting the initiation
      of DNA chain elongation away from the iterons were functionally more important
      than ones in the inverted orientation. We consider that this functional
      difference reflects the inherent properties of the initiation mechanism of
      RSF1010 DNA replication.

PMID- 8139917
TI  - Transposase A binding sites in the attachment sites of bacteriophage Mu that are
      essential for the activity of the enhancer and A binding sites that promote
      transposition towards Fpro-lac.
AB  - In this paper we determine which of the A binding sites in the attachment sites
      of phage Mu are required for the stimulatory activity of the transpositional
      enhancer (IAS). For this purpose the transposition frequencies of mini-Mu's with
      different truncated attachment sites to an Ftet target were measured both in the
      presence and the absence of the IAS. The results show that in our in vivo assay
      the L3 and R3 sites are dispensable for functioning of the IAS. An additional
      deletion of L2 or R2 however abolishes the stimulating activity of the enhancer
      suggesting an interaction between A molecules bound to these sites and the IAS.
      The residual transposition activity of a IAS-containing mini Mu in which R2 (and
      R3) are deleted is much lower than the activity of the comparable construct
      without the IAS. This means that in the absence of R2 the IAS is inhibiting
      transposition. Such an inhibition is not observed when L2 (and L3) are deleted.
      This suggests that the IAS interacts with the attachment sites in an ordered
      fashion, first with attL and then with attR. Furthermore we show that mini-Mu
      transposition is enhanced when Fpro-lac is used as a target instead of Ftet. We
      show that this elevated transposition is dependent on the Mu A binding sites
      L2,L3 and R2. These sequences could possibly mediate an interaction between the
      mini-Mu plasmid and sequences present on Fpro-lac.

PMID- 8139918
TI  - Interactions between Sindbis virus RNAs and a 68 amino acid derivative of the
      viral capsid protein further defines the capsid binding site.
AB  - In previous studies of encapsidation of Sindbis virus RNA, we identified a 570nt
      fragment (nt 684-1253) from the 12 kb genome that binds to the viral capsid
      protein with specificity and is required for packaging of Sindbis virus defective
      interfering RNAs. We now show that the capsid binding activity resides in a
      highly structured 132nt fragment (nt 945-1076). We had also demonstrated that a
      68 amino acid peptide derived from the capsid protein retained most of the
      binding activity of the original protein and have now developed an RNA mobility
      shift assay with this peptide fused to glutathione-S-transferase. We have used
      this assay in conjunction with the original assay in which the intact capsid
      protein was immobilized on nitrocellulose to analyze more extensive deletions in
      the 132-mer. All of the deletions led to a reduction in binding, but the binding
      of a 5' 67-mer was enhanced by the addition of nonspecific flanking sequences.
      This result suggests that the stability of a particular structure within the
      132nt sequence may be important for capsid recognition.

PMID- 8139919
TI  - Infrared linear dichroism studies of DNA-drug complexes: quantitative
      determination of the drug-induced restriction of the B-A transition.
AB  - The B-A transition of films or fibers of NaDNA occurs at a relative humidity of
      75-85%. The fraction of DNA that changed the conformation from B to A form can be
      determined quantitatively by infrared linear dichroism. DNA-binding drugs can
      'freeze' a fraction of DNA in the B form. This fraction of DNA is in the B form
      and cannot be converted to A-DNA even at a reduced relative humidity of 54%. The
      'freezing' potentiality of various drugs can be described by the 'freezing'
      index, FI, expressed in base pairs per added drug. Drugs with a high value of FI
      (more than eight base pairs per drug) were observed among both intercalating and
      groove-binding drugs. High values of FI imply restriction of the conformational
      flexibility of DNA significantly going beyond the binding site of the drug. This
      long-range effect of drugs on the conformational flexibility of DNA may be
      connected with the molecular mechanism of drug action. The freezing index FI is a
      new quantitative parameter of drug-DNA interaction that should be considered as a
      valuable tool for drug design.

PMID- 8139920
TI  - Sequences affecting the V(D)J recombinational activity of the IgH intronic
      enhancer in a transgenic substrate.
AB  - The immunoglobulin heavy chain intronic transcriptional enhancer (E mu) is part
      of a complex cis-regulatory DNA region which has notably been shown to modulate
      V(D)J rearrangements of associated variable gene segments. We have used
      recombination substrates comprised of the E mu enhancer together with various
      lengths of additional downstream mu sequences to assess the individual
      contribution of those sequences to the V(D)J recombinational regulatory activity.
      Surprisingly, in the absence of large amounts of mu sequences, substrate
      rearrangements were not detected in Southern blot analyses of the lymphoid
      tissues from independent transgenic mice, but were readily detectable following
      transfection into cultured pre-B cells. A short mu segment which includes matrix
      association regions (MARs) was not sufficient to restore high levels of
      rearrangements within the reporter transgenes. However, additional experiments
      demonstrated that the mu sequences are dispensable for V(D)J recombination in
      transgenic thymuses, implying a suppressive effect exerted by the vector
      sequences left in the transgenic insert, when they are attached near the E mu
      regulatory region. This suppression of V(D)J recombination, which correlates with
      an hypermethylation of the transgenes, is discussed in view of previously
      reported transgenic and gene targeting experiments.

PMID- 8139921
TI  - Evaluation of quantitative variation in gene expression.
AB  - We investigate the behaviour of the gene-expression rate as a statistical
      variable using autoradiographic data for 39 transcripts from a heterogeneous set
      of 80 breast-tissue cultures. Despite standardization, the data distributions of
      all transcripts showed intervals of normality and intervals of systematic
      departure from normality which most frequently resulted in a significant skewness
      and/or kurtosis. Non-normal shapes are attributed to modulation of gene
      expression. This statistical particularity creates difficulties in the evaluation
      of differences among specimens. Using classical parametric and non-parametric
      procedures for normal and non-normal variation, respectively, we demonstrate that
      large differences in optical density are neither necessary nor sufficient for
      associating expression rates with biological factors. The transcripts coding for
      the metalloprotease stromelysin-3 (ST3) and for the receptor to insulin-like
      growth factors (IGFR) are used as examples and their variation is presented in
      detail. ST3 expression appeared to be specifically associated with mammary stroma
      fibroblasts derived from post-radiation fibrosis lesions. IGFR was expressed at
      higher rates in mammary gland and skin fibroblasts than in mammary epithelial
      cells and was subject to frequent and strong modulation.

PMID- 8139922
TI  - Protein/DNA crosslinking of a TFIID complex reveals novel interactions downstream
      of the transcription start.
AB  - A protein--DNA complex containing TFIID has been analyzed by crosslinking. The
      TBP subunit of TFIID crosslinked to the TATA element but not to any of the
      regions further downstream which were tested. A 150 kd polypeptide, which
      corresponds in size to one of the TBP-associated factors (TAFs), crosslinked to a
      region between +10 and +15 and a second region between +35 and +47. Another
      polypeptide of greater than 205 kd (also a potential TAF) crosslinked
      preferentially to the region between +35 and +42. The +10 to +15 region has been
      recently implicated in hsp70 promoter recognition by TFIID, and the most
      downstream contacts overlap with the region where RNA polymerase II pauses on the
      hsp70 promoter in noninduced cells. Crosslinking revealed that as the salt
      concentration was increased, the TBP interaction was largely unaffected whereas
      the protein/DNA interactions downstream of the TATA element were disrupted. We
      propose that during the formation of a transcription complex, TATA-dependent
      interactions could be disrupted in the vicinity of the start site and the region
      immediately downstream. A protein contact downstream of +35 might function in
      pausing polymerase.

PMID- 8139923
TI  - Inhibition of herpes simplex virus infection by ectopic expression of neuronal
      splice variants of the Oct-2 transcription factor.
AB  - Herpes simplex virus (HSV) is capable of lytic replication in most cells, such
      replication in epithelial cells resulting in the mucocutaneous lesions observed
      following in vivo infection. In addition however, the virus also establishes
      asymptomatic latent infections in sensory neurons which serve as a reservoir for
      further cycles of peripheral lytic infections. These latent infections are
      dependent upon the inhibition of viral immediate-early (IE) gene expression via
      the octamer-related TAATGARAT motif in the IE promoters resulting in the failure
      of the viral lytic cycle. Here we show that the ectopic expression of neuronal
      isoforms of the octamer/TAATGARAT-binding transcription factor Oct-2 in
      permissive BHK cells represses IE gene expression following HSV infection and
      inhibits the viral lytic cycle whereas the B lymphocyte isoform of Oct-2 does not
      have this effect. These results suggest that the neuronal isoforms of Oct-2 play
      a critical role in rendering neuronal cells non-permissive for the viral lytic
      cycle thereby allowing the establishment of latent infection. Moreover, this is
      the first time that the ectopic expression of a cellular transcription factor has
      been shown to inhibit infection with any virus, raising the possibility of
      therapeutically inhibiting lytic viral infections by inducing such ectopic
      expression.

PMID- 8139924
TI  - An operator associated with autoregulation of the repressor gene in actinophage
      phiC31 is found in highly conserved copies in intergenic regions in the phage
      genome.
AB  - Previous reports have suggested that the repressor gene, c, of phiC31 is
      autoregulated and that likely operators are conserved inverted repeat sequences
      (CIRs1&2) located just upstream of the promoters, cp1 and cp2. Evidence is now
      presented that the CIRs 1&2 are indeed binding sites for one of the three
      inframe, N-terminally different protein isoforms of 42, 54 and 74 kDa produced by
      the c gene. A cp1-aphII fusion was repressed in a Streptomyces coelicolor A3(2)
      phiC31 lysogen and characterisation of an operator-constitutive (Oc) mutant
      showed a single mutation in CIR-1. CIR-1 containing fragments were retarded in
      electrophoresis gels by the 42 kDa repressor protein isoform and this retardation
      was inhibited by the addition of competing DNA fragments containing either CIR-1
      or CIR-2. Using a combination of Southern blotting and analysis of available DNA
      sequence we also show that at least 18 copies of the CIRs are present throughout
      the phiC31 genome. Alignment of 9 CIR sequences showed that 8 contained a
      perfectly conserved 17 bp core whilst the exception had a single mismatch. The
      core includes a 16 bp inverted repeat (IR), and is usually part of a more
      extensive and less highly conserved palindrome. When superimposed on a previously
      derived transcription map of the early region, the CIRs lie in intergenic regions
      associated with transcription initiation and/or termination.

PMID- 8139925
TI  - A cellular repressor regulates transcription initiation from the minute virus of
      mice P38 promoter.
AB  - We previously reported that the P38 promoter of minute virus of mice (MVM) is
      trans activated by the viral nonstructural protein, NS1, through an interaction
      with a downstream promoter element designated DPE. In this communication we
      report the identification of a distinct downstream promoter element which
      inhibits transcription from the P38 promoter in vitro, in the absence of the DPE.
      Removal of 34 bp from the region between +95 and +129 downstream from the P38
      initiation start site relieved inhibition of transcription in whole-cell extract.
      Inhibition was also relieved by the addition, to the transcription reaction, of
      excess DNA fragments which span the putative inhibiting element. This indicated
      the involvement of a trans-acting factor, in inhibition of transcription from the
      P38. Gel retardation experiments demonstrated the specific binding of a cellular
      protein to the inhibitory element. This P38 inhibitory element shows spacing and
      orientation dependence as well as promoter specificity. The regulation of viral
      transcription by a cellular repressor may play an important role in obtaining a
      fine temporal order of viral gene expression during the course of infection.

PMID- 8139926
TI  - Alternative splicing of the guanine nucleotide-binding regulatory protein Go
      alpha generates four distinct mRNAs.
AB  - Go alpha a guanine nucleotide-binding (G) protein abundant in brain and other
      neural tissues, has been implicated in ion channel regulation. Concerted efforts
      in several laboratories have revealed multiple Go alpha mRNAs and protein
      isoforms in different contexts. Go alpha is a single copy gene in mammalian
      species, although the structure, number and tissue localization of Go alpha mRNAs
      reported by investigators are inconsistent. To define the cell-specific
      expression of alternatively spliced variants of Go alpha mRNA, we employed
      several strategies, including Northern hybridizations with sequences-specific
      oligonucleotides, selective digestions of Go alpha mRNA using RNase H, and
      adaptations of the polymerase chain reaction. Four distinct alternatively spliced
      variants were identified, a 5.7-kb Go alpha 2 mRNA and three Go alpha 1 mRNAs
      with different 3' UTRs. The UTRs of the three Go alpha 1s are composed of
      different combinations of what have been referred to as UTR-A and UTR-B. The
      sequences of the spliced segments are well conserved among mammalian species,
      suggesting a functional role for these alternatively spliced 3' UTRs in post
      transcriptional and/or tissue-specific regulation of Go alpha expression. The
      position of the intron-exon splice boundary at nucleotide 31 following T of the
      TGA stop codon is conserved in the Gi alpha 2 and Gi alpha 3 genes, consistent
      with the notion that similar alternative splicing of 3' UTRs occurs in products
      of these related genes.

PMID- 8139929
TI  - Identification of enriched sequences from a cDNA subtraction-hybridization
      procedure.

PMID- 8139927
TI  - Analysis of the imperfect octamer-containing human immunoglobulin VH6 gene
      promoter.
AB  - The octamer sequence ATGCAAAT is highly conserved in the promoter of
      immunoglobulin heavy and light chain genes and is one of the sequence motifs
      involved in the control of transcription of these genes. The promoter region of
      an human immunoglobulin heavy chain variable gene, the sole member of the VH6
      gene family, was found to differ from other VH gene promoters: it contains
      neither the conserved octamer motif nor a heptamer sequence, and generally bears
      little resemblance to other VH gene transcriptional control regions. An imperfect
      octamer sequence with a single nucleotide substitution (AgGCAAAT) is located 108
      bp upstream of the ATG translation start site, and 81 bp upstream of the
      transcription initiation site. We sought to determine which sequence elements
      within the VH6 promoter were responsible for transcription initiation by creating
      progressive deletions of a 1 kb fragment from this region and testing their
      ability to function as promoter elements in B and non-B cells (HeLa). The minimum
      fragment required for full promoter function was 110 bp, but a fragment with only
      65 bp retained 30-50% activity in B cells. Similar levels of transcription were
      seen when the -146 bp promoter containing two point mutations in the imperfect
      octamer was tested. Mutation of a possible pyrimidine box sequence located
      downstream of the TATA box was shown to have only a minor effect (10-30%) on
      transcription when three nucleotides were changed. Surprisingly, CAT activity was
      not B cell-specific, as all constructs had virtually the same activity in several
      B cell lines and in HeLa cells. Removal of the TATA box led to a 50% reduction in
      CAT activity, and the region upstream of the TATA box functioned as a promoter in
      both orientations. The transcriptional activity of the VH6 promoter was virtually
      enhancer independent: only a minor increase was observed when the immunoglobulin
      or SV40 enhancer was added to the promoter construct. Electrophoretic mobility
      shift assays of transcription factor binding to the region around the imperfect
      octamer indicated that binding was weak when nuclear extracts from either B cells
      or HeLa cells were used. The amount of complex shifted was increased by mutating
      the imperfect octamer to a perfect one. Chimeras produced between the VH6
      promoter and a B cell-specific promoter from a member of the human VH2 gene
      family demonstrated that the lack of tissue specificity was due to the absence of
      a repressor of non-B cell transcription in the VH6 promoter. These results
      indicate that the VH6 promoter is relatively simple, requiring little more than
      the TATA element and the imperfect octamer, and transcription from this promoter
      lacks B cell specificity and is not dependent on the enhancer element.

PMID- 8139930
TI  - 'Broad-range' DGGE for single-step mutation scanning of entire genes: application
      to human phenylalanine hydroxylase gene.

PMID- 8139928
TI  - RNP1, a new ribonucleoprotein gene of the yeast Saccharomyces cerevisiae.
AB  - A previously unidentified ribonucleoprotein (RNP) gene of yeast has been cloned
      and sequenced. The gene, named RNP1, was found adjacent to a previously sequenced
      gene encoding the second gene for ribosomal protein L4. RNP1 contains two RNA
      Recognition Motifs (RRM), [alternatively known as RNA binding Domains (RBD)], but
      unlike most RNP genes does not contain any auxiliary simple sequence domains. The
      first RRM (RRM1) most resembles RRM domains found in the hnRNP A/B class of RNP
      proteins. The second RRM (RRM2) most resembles a RRM so far seen only in the
      single RRM of the yeast SSB1 gene. Two null mutants of RNP1 that were created, a
      frameshift disruption and a complete deletion of the gene, were viable,
      demonstrating that the gene is not essential for cell growth. Two double null
      mutants of yeast RNP genes that were created (delta RNP1/delta SSB1 and delta
      SSB1/delta NPL3) were also viable. A fragment identical in size to the RRM1
      domain could be amplified by PCR from the DNA of fungi, plants, and animals,
      using primers matching the ends of this domain, indicating that the structure of
      RRM1 is conserved. Another potential open reading frame on the same cloned
      fragment of DNA encodes a gene product whose structure resembles that of a seven
      transmembrane-segment membrane receptor protein.

PMID- 8139931
TI  - A method for locating O6-methylguanine residues in DNA.

PMID- 8139932
TI  - A new method for strand discrimination in sequence-directed mutagenesis.

PMID- 8139933
TI  - Introduction of arbitrary sequences into genes by use of class IIs restriction
      enzymes.

PMID- 8139934
TI  - Optimization of primer sequences for mouse scFv repertoire display library
      construction.

PMID- 8139935
TI  - Flexible approaches. Interview by Catharine Sadler.

PMID- 8139936
TI  - Discharge duty?

PMID- 8139937
TI  - Fighting words. Interview by Joanna Lyall.

PMID- 8139939
TI  - Nurse practitioners. Special but not specialist.

PMID- 8139938
TI  - Buying time.

PMID- 8139940
TI  - Nurse practitioners. Practising independently. Interview by Sue Smith.

PMID- 8139941
TI  - Shock treatment.

PMID- 8139942
TI  - Staff support: stressbusters.

PMID- 8139943
TI  - Chronic illness: me and you and me.

PMID- 8139944
TI  - Next stop Moscow.

PMID- 8139945
TI  - Complementary medicine. Osteopathy.

PMID- 8139947
TI  - Guide to pressure-relieving beds and mattresses. Soft options.

PMID- 8139946
TI  - Pressure relief. Better than cure.

PMID- 8139948
TI  - Mental health. Still life on Leros.

PMID- 8139949
TI  - Mental health. Taking back control.

PMID- 8139950
TI  - Mental health. Lunatic poet.

PMID- 8139951
TI  - Sign of the times.

PMID- 8139952
TI  - Blockage in the system.

PMID- 8139953
TI  - Emergency rations.

PMID- 8139954
TI  - Are you getting enough?

PMID- 8139955
TI  - Night nursing. Reflex action.

PMID- 8139956
TI  - Night nursing. Thirst for knowledge.

PMID- 8139957
TI  - Making sense of brain stem death.

PMID- 8139958
TI  - Springing the trap.

PMID- 8139960
TI  - Computing. A tool for assessment.

PMID- 8139959
TI  - Tropical treatment.

PMID- 8139961
TI  - Computing. A specialist perspective.

PMID- 8139962
TI  - Force of habits.

PMID- 8139963
TI  - Learning disabilities. Caring teams.

PMID- 8139964
TI  - Learning disabilities. Power to parents.

PMID- 8139966
TI  - New advice on wearing gloves.

PMID- 8139965
TI  - Learning disabilities. Hear our voice.

PMID- 8139967
TI  - Beyond bingo.

PMID- 8139968
TI  - Vein hopes.

PMID- 8139969
TI  - Safe inside.

PMID- 8139970
TI  - Dementia. Communal confusion.

PMID- 8139972
TI  - Sharing the burden.

PMID- 8139971
TI  - Dementia. Voyage of discovery.

PMID- 8139974
TI  - Just a laugh?

PMID- 8139973
TI  - Lactation mastitis.

PMID- 8139975
TI  - Complementary therapies. Study rules.

PMID- 8139976
TI  - Mental health. Given a voice.

PMID- 8139977
TI  - Systems of life. The eye and vision. 3.

PMID- 8139978
TI  - Call to protect staff with HIV.

PMID- 8139979
TI  - Infection control. Decontamination quality.

PMID- 8139980
TI  - Infection control. Unhygienic practices.

PMID- 8139981
TI  - HIV-positive nurses and other health workers must be guaranteed anonymity.

PMID- 8139983
TI  - [Guidelines on AIDS and first aid in the workplace].

PMID- 8139982
TI  - Monks plan AIDS hostel in north Wales.

PMID- 8139984
TI  - Safe motherhood programme.

PMID- 8139985
TI  - TNAI workshop on nursing care management of people with human immunodeficiency
      virus (HIV): a report.

PMID- 8139986
TI  - A glimpse of the nursing situation in Goa State: a report.

PMID- 8139988
TI  - Nurses' education and their role in health programmes.

PMID- 8139987
TI  - American Nurses Association & TNAI's joint project on HIV/AIDS. A report of
      workshop to train the trainers.

PMID- 8139989
TI  - Gait: its significance and nursing aspect.

PMID- 8139990
TI  - Nursing resource planning: approaches and emphasis.

PMID- 8139991
TI  - Preliminary experience with nonthoracotomy implantable cardioverter
      defibrillators in young patients. The Medtronic Transvene Investigators.
AB  - Implantable cardioverter defibrillators represent an important treatment option
      for patients with life-threatening tachyarrhythmias. However, the requirement for
      surgical access to the thorax contributes to significant procedural morbidity
      with ICD implantation. This study was performed to assess an initial experience
      with a nonthoracotomy approach to ICD lead implantation in young patients. An
      international survey identified 17 patients, ranging in age from 12-20 years
      (mean = 16.7 +/- 2.4) and weighing from 33-89 kg (mean = 60.6 +/- 13.3), who had
      undergone placement of the Medtronic Transvene defibrillator lead system. Implant
      indications were aborted sudden cardiac death in 15 patients and recurrent
      ventricular tachycardia or familial sudden death in 2 patients. At a median
      follow-up of 7.9 months, 9 of 17 patients had received at least one ICD therapy.
      There have been no deaths. Complications included patch or generator erosion (3
      patients), lead dislodgement (1 patient), and ICD system infection requiring
      explanation (1 patient). The initial experience with nonthoracotomy ICDs in young
      patients appears promising. This approach may be particularly advantageous for
      patients who have undergone prior thoracotomy. Prospective clinical trials will
      be required to establish the applicability of these lead systems to select
      patient populations.

PMID- 8139992
TI  - Importance of an individually programmed atrioventricular delay at rest and on
      work capacity in patients with dual chamber pacemakers.
AB  - Despite higher costs, expenditure, and the necessity of repeatedly reprogramming
      of dual chamber pacemakers, they are increasingly implanted to achieve an optimal
      work capacity. The influence of an individually programmed atrioventricular (AV)
      delay between 100-250 msec on physical work capacity in 12 patients (68 +/- 16
      years) with dual chamber pacemakers implanted for high degree AV block was
      studied. During radionuclide ventriculography at rest the "optimal AV delay" with
      the maximal achieved left ventricular ejection fraction and the "most unfavorable
      AV delay" with the least achieved ejection fraction were determined. The ejection
      fraction at rest with the "optimal AV delay" was 51 +/- 14% and with the "most
      unfavorable AV delay" 45 +/- 15% (P < 0.001). In random order each patient was
      assigned to either AV delay and a spiroergometry was performed to determine
      maximum oxygen uptake (max VO2), which correlates best with work capacity, at a
      respiratory quotient of 1.1. The results show neither a difference in maximum
      oxygen uptake (1,262 +/- 446 mL/min with the optimal AV delay, 1,248 +/- 400
      mL/min with the most unfavorable AV delay, respectively) nor in heart rate, blood
      pressure, exercise duration, maximal workload, and minute ventilation. Thus, an
      individually programmed AV delay affects left ventricular ejection fraction at
      rest. In contrast, an individually programmed AV delay has no influence on
      physical work capacity in patients with a dual chamber pacemaker.

PMID- 8139993
TI  - Oncology nurses' attitudes, perceptions, and knowledge of quality-of-life
      assessment in patients with cancer.
AB  - PURPOSE/OBJECTIVES: To provide an overview of the current attitudes and
      perceptions of oncology nurses regarding the relevance and measurability of
      quality of life (QOL) in patients with cancer. DESIGN AND SETTING: Exploratory
      survey conducted at a scientific exhibit of QOL instruments at the 1990 Oncology
      Nursing Society Congress held in Washington, DC. SAMPLE: Convenience sample of
      621 nurses visiting the exhibit. METHODS: Subjects completed two questionnaires
      addressing opinions regarding the impact of treatment on QOL, the importance of
      QOL as an outcome measure, the current status of QOL assessment, barriers to
      measuring QOL, and knowledge about QOL measurement tissues. MAIN OUTCOME
      MEASURES: Results of answers to questionnaire items overall as well as selected
      demographic variables. FINDINGS: Chemotherapy was thought to have the greatest
      negative impact on QOL, and vomiting, nausea, and tiredness were judged to be the
      side effects of treatment that most commonly affected QOL. QOL was judged as
      important an outcome measure as tumor response, toxicity, and survival.
      Generally, nurses were knowledgeable regarding QOL measurement issues; however,
      many of the respondents indicated that they believed valid QOL instruments did
      not exist or that QOL could not be objectively quantified. CONCLUSIONS: Nurses
      value QOL as an outcome measure of cancer treatment but lack knowledge regarding
      its measurability, particularly with respect to reliable tools and available time
      to assess it well. IMPLICATIONS FOR NURSING PRACTICE: Nurses can be instrumental
      in incorporating QOL measurement as an outcome of treatment and development of
      brief self-administered tools. Commentary on this research and author response is
      included at the conclusion of the article.

PMID- 8139994
TI  - ONS Board comments on recent guest editorial.

PMID- 8139995
TI  - Documentation forms for monitoring occupational surveillance of healthcare
      workers who handle cytotoxic drugs.
AB  - PURPOSE/OBJECTIVES: To develop a procedure for medical surveillance of healthcare
      workers who handle cytotoxic drugs. DATA SOURCES: Literature review and
      guidelines published by the Occupational Safety and Health Administration and the
      National Institute for Occupational Safety and Health. INFORMATION SELECTION:
      Studies of possible exposure screening tests, congenital defects in offspring,
      and case studies. DATA SYNTHESIS: Some degree of risk exists in handling
      cytotoxic drugs, but no reliable screening test for cytotoxic drug exposure has
      been developed. Reproductive hazards are possible when protective equipment is
      not used. Areas to be addressed when devising surveillance procedures include who
      to cover, what baseline data to gather, what periodic monitoring will be
      necessary (and at what interval it will be conducted), how to handle exposure
      incidents, and what documentation system will be used. CONCLUSIONS: A procedure
      using a baseline risk factor form and a yearly monitoring questionnaire was
      devised and implemented. Forms contain documentation of worker teaching.
      IMPLICATIONS FOR NURSING PRACTICE: Most often, nurses are the healthcare workers
      who handle cytotoxic drugs. A consistent approach to monitoring healthcare
      workers is facilitated by using a defined procedure and standardized forms.

PMID- 8139996
TI  - Patients' vacations can create challenges.

PMID- 8139997
TI  - Nurses' teaching guide aids in understanding new drug.

PMID- 8139998
TI  - Alternate technique decreases number of needle-sticks.

PMID- 8139999
TI  - Fatigue and the cancer experience: the state of the knowledge.

PMID- 8140000
TI  - Behavioral adjustment and self-esteem of school-age children of women with breast
      cancer.
AB  - PURPOSE/OBJECTIVES: To describe children's psychosocial adjustment to their
      mother's breast cancer and to compare their level of adjustment with normative
      data and with the level of adjustment of children of women with fibrocystic
      breast disease or diabetes. Hypotheses tested were (a) children of women with
      breast cancer would be most negatively affected and (b) families of mothers with
      fibrocystic breast disease would require less family adaptation than families of
      women with breast cancer or diabetes. DESIGN: One component of a larger
      longitudinal survey. SETTING: University-based physician clinic in a metropolitan
      area in the Northwestern United States. SAMPLE: Mothers, predominantly Caucasian,
      with medically controlled diabetes mellitus (n = 18), nonmetastatic breast cancer
      (n = 13), or biopsy-proven fibrocystic breast disease (n = 17) and their children
      (N = 48), who ranged in age from 6 to 12. METHODS: Five in-home interviews
      conducted at four-month intervals. MAIN OUTCOME MEASURES: Behavioral adjustment
      using the Louisville Behavior Checklist (maternal report) and the Zeitlin Coping
      Inventory (nurse-observer report) and self-esteem using the Personal Attribute
      Inventory for Children (children's self-report). FINDINGS: Children of women with
      breast cancer scored better than average on behavioral adjustment (mothers'
      ratings) and were judged by nurse observers to be better behaviorally adjusted
      than children in the noncancer illness groups. Children of women with breast
      cancer and of women with diabetes tended to score significantly lower on self
      esteem than the comparative sample. CONCLUSIONS: Measures of childhood adjustment
      to chronic medical illness in mothers need to distinguish between behavioral
      adjustment and self-esteem. Discrepancies between child ratings and mother and
      nurse-observer ratings suggest that differences exist. IMPLICATIONS FOR NURSING
      PRACTICE: Findings are preliminary in nature, and other explanations for findings
      must be ruled out. However, if a child's self-appraisal is affected negatively by
      the mother's illness, it would be appropriate to identify ways to increase
      emotional and physical exchange with the child and to interpret inaccessibility
      in ways that protect the child's positive self-appraisal.

PMID- 8140001
TI  - Obstacles to cancer care: focus on the economically disadvantaged.
AB  - PURPOSE/OBJECTIVES: To provide additional documentation of the unmet cancer
      prevention and control needs of poor Americans. DESIGN AND SETTING: Qualitative
      analysis of testimony provided at American Cancer Society hearings on cancer and
      the poor. SAMPLE: 46 economically disadvantaged individuals with personal
      experiences with cancer. METHODS: Review of transcription of oral testimony and
      qualitative analysis for recurrent themes to identify common obstacles to cancer
      care. FINDINGS: Six major obstacles were identified: care was deferred because of
      costs; care was described as "fragmented," "impersonal," and "symptomatic;"
      patients were discouraged from worrying about bodily changes; patients were
      discouraged from seeking state-of-the-art care; poor patients experienced
      difficulty communicating their needs and concerns; and poverty interfered with
      efforts to participate in volunteer activities. CONCLUSIONS: Testimony is
      suggestive of the problems that poor patients with cancer face. Challenges to
      improve the situation include expanding and extending diagnostic, treatment, and
      rehabilitative services to the poor; facilitating education and prevention; and
      further research to document the scope of the problem. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses should engage in the debate over healthcare reform and take
      advantage of the opportunities to define and participate in the development of
      procedures, strategies, and systems for removing obstacles to quality cancer
      prevention and care for the poor.

PMID- 8140002
TI  - Making a difference in the 21st century: are oncology nurses ready?

PMID- 8140003
TI  - New identities: the changing profile of patients with cancer, their families, and
      their professional caregivers.
AB  - PURPOSE/OBJECTIVES: To discuss and project cancer care needs and a vision of
      oncology nursing in the next century. DATA SOURCES: Scholarly, professional, and
      governmental sources of information. DATA SYNTHESIS: Projections of a changed
      patient/family profile, social support dilemmas, and a new "hybrid" oncology
      nurse. CONCLUSIONS: Opportunities for nurses, resulting from these projections,
      include roles as minority needs specialist, director of new care-delivery models,
      facilitator of intergenerational support teams, overseer of neighborhood-based
      care systems, multispecialty nursing care provider, cancer care policy activist.
      IMPLICATIONS FOR NURSING PRACTICE: Nursing education, community models, and
      current care-delivery settings will all be affected by the projected changes and
      will all need to consider adjusting to meet the demands that will be placed on
      them to facilitate change.

PMID- 8140004
TI  - New approaches: innovations in cancer prevention, diagnosis, treatment, and
      support.
AB  - PURPOSE/OBJECTIVE: To discuss and project changes in cancer care in the 21st
      century. DATA SOURCES: Projections are based on synthesis of multiple scholarly,
      professional, and governmental information sources. DATA SYNTHESIS: Changes will
      be reflected in the areas of patient subgrouping for more effective prevention
      and treatment; a redesigned therapeutic paradigm; a mind-body renaissance
      emphasizing holism and quality of life; and an accentuated influence of ethics on
      oncology nursing practice arising from healthcare reform and new scientific
      understanding of the human gene. CONCLUSIONS: Opportunities for nurses resulting
      from these changes include roles as genetic-risk analysts, health-education media
      designers, patient readiness evaluators, technology accessors, partners in a
      holistic care center, and treatment options advisors. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses will need to respond to these challenges by expanding their
      knowledge base with respect to genetics and computer science, refining the
      interactive skills that are necessary to address the psychosocial aspects of
      cancer care, and assimilating new technology while designing strategies to
      minimize the dehumanizing consequences of technology dependency.

PMID- 8140005
TI  - New systems: the restructuring of cancer care delivery and economics.
AB  - PURPOSE/OBJECTIVE: To review and discuss the economic and care delivery
      implications of the healthcare reform currently being debated. DATA SOURCES:
      Projections are based on synthesis of multiple scholarly, professional, and
      governmental sources of information. DATA SYNTHESIS: Future projections regarding
      the hallmarks of healthcare reform (e.g., universal access, fewer payors,
      rationing of care), changes in practice settings, and novel communications
      technologies are discussed. CONCLUSIONS: Opportunities for nurses resulting from
      these changes include roles as resource allocators, cost-benefit analysis, cancer
      system liaisons, satellite-program builders, and quality-assessment experts.
      IMPLICATIONS FOR NURSING PRACTICE: Changes will challenge nurses to assume
      multiple responsibilities as clinicians, administrators, educators, and
      researchers who will need to integrate input from numerous sources to make
      decisions that take into account competing and contradictory factors.

PMID- 8140006
TI  - Taking command of the future: getting ready now for the 21st century.

PMID- 8140007
TI  - Small cell lung cancer: pathophysiologic mechanisms and nursing implications.
AB  - PURPOSE/OBJECTIVES: To review current incidence and treatment perspectives for
      small cell lung cancer (SCLC). DATA SOURCES: Published articles, book chapters,
      American Cancer Society materials. DATA SYNTHESIS: SCLC constitutes 20%-30% of
      lung cancer cases and accounts for 40,000 deaths annually. Characterized by rapid
      cell division, SCLC is very sensitive to radiation and chemotherapy; however,
      long-term survival rates are very low. A number of paraneoplastic syndromes are
      associated with this disease, thereby increasing the medical and nursing
      management challenges. CONCLUSIONS: Because SCLC usually is diagnosed late in the
      disease process and survival rates are poor, quality of life and palliation of
      metastatic symptoms (e.g., pain, breathing difficulties) are important focuses of
      care. Smoking deterrence and cessation programs, as well as early detection of
      lesions, are key to reducing incidence and mortality. IMPLICATIONS FOR NURSING
      PRACTICE: Nursing care focuses on promoting comfort and preventing and managing
      disease and treatment complications. Nursing diagnoses include ineffective airway
      clearance, impaired gas exchange, pain, altered nutrition, activity intolerance,
      and ineffective coping. A patient care standard is presented.

PMID- 8140008
TI  - To screen or not to screen?

PMID- 8140009
TI  - Non-epileptic attack disorder.

PMID- 8140010
TI  - Unusual manifestations of craniofacial fibrous dysplasia: clinical,
      endocrinological and computed tomographic features.
AB  - Clinical, endocrinological and computed tomographic features of three patients
      with unusual manifestations or complications of craniofacial involvement of
      fibrous dysplasia are presented. One patient with polyostotic fibrous dysplasia
      presented in late pregnancy with acute onset of bilateral optic nerve compression
      and blindness secondary to a rapidly expanding mass of fibrous dysplasia tissue
      involving the sphenoid, pituitary and optic chiasm regions. A second patient with
      polyostotic fibrous dysplasia developed thyrotoxicosis and probable
      gigantism/acromegaly in keeping with a rare form of McCune-Albright syndrome.
      Extensive bony distortion of the skull and facial bones by fibrous dysplasia made
      clinical recognition of these complications more difficult. A third patient had
      monostotic fibrous dysplasia with marked sclerosis of the sphenoid bone on plain
      radiographs which mimicked appearances of a meningioma and resulted in a negative
      craniotomy as computed tomography was not yet available at the time of
      presentation. Each case demonstrated rare complications of craniofacial fibrous
      dysplasia and highlighted the wide spectrum of appearances in which it may
      manifest, often resulting in overlap and diagnostic confusion with other disease
      processes. The value of computed tomography in assessment is emphasized.

PMID- 8140011
TI  - Anti-mitochondrial antibodies in patients with Graves' disease may not signify
      primary biliary cirrhosis.
AB  - Two patients with Graves' disease were incidentally found to have anti
      mitochondrial antibodies by immunofluorescence in the absence of symptoms,
      clinical signs or biochemical evidence of liver dysfunction. Anti-mitochondrial
      antibody titres became undetectable in both patients on follow-up. Screening of
      the patients' sera by immunoblotting against the purified antigens of the M2
      complex was negative. We conclude that in these cases, anti-mitochondrial
      antibodies detected by immunofluorescence were directed against antigens other
      than the primary biliary cirrhosis-associated M2 complex and therefore did not
      signify subclinical primary biliary cirrhosis.

PMID- 8140012
TI  - Perforated typhoid enteritis in children.
AB  - A prospective study of 65 patients with perforated typhoid enteritis managed
      operatively over a 3 year period at a university hospital is presented. There
      were 45 males and 20 females with ages ranging from 5 to 15 years. Presenting
      symptoms were fever, abdominal pain, vomiting and either diarrhoea or
      constipation. All the patients were subjected to surgery and 56 (86%) underwent
      two-layer bowel closure after freshening of ulcer margins. The overall mortality
      rate in this study was 20% and was adversely influenced by the increasing
      duration of perforation, presence of shock and faecal peritonitis. Early surgery
      after prompt and adequate resuscitation is life saving. However, prevention of
      typhoid fever by providing safe drinking water and better sanitary conditions
      appears to offer the best chance of decreasing the high rates of mortality and
      morbidity of this deadly disease.

PMID- 8140013
TI  - Butterfat absorption--a valuable screening test in malabsorption.
AB  - The diagnosis of intestinal malabsorption is difficult to make without the use of
      specific tests such as endoscopic retrograde cholangiopancreatography (ERCP) or
      duodenal biopsy which are invasive and potentially hazardous. Faecal fat
      estimation or C14 Triolein breath tests have limitations as screening tools are
      time consuming and expensive. The butterfat absorption test (BFAT) is, in
      contrast, a simple, quick and cheap test for fat malabsorption. We have assessed
      the performance of this test in a blinded retrospective study of all such
      procedures performed in a teaching hospital over an 8 year period. One hundred
      and fourteen cases of suspected malabsorption had one or more butterfat tests.
      These were divided into absorbers and malabsorbers without knowledge of the
      butterfat test results. We found the butterfat test to have a sensitivity of 88%
      and a specificity of 94% using a cut-off of 20 light-scattering intensity units
      to discriminate normal from abnormal tests. At this level, predictive values are
      91% for a positive result and 92% for a negative. These results are similar to
      those reported with the C14 Triolein breath test and adjusted faecal fats. We
      conclude that the butterfat test is a simple, cheap and effective screening test
      in the diagnosis of malabsorption.

PMID- 8140015
TI  - The changing health service.

PMID- 8140014
TI  - Bilateral parotid enlargement as a presenting feature of bulimia nervosa in a
      post-adolescent male.
AB  - An unusual case of bulimia nervosa in a post-adolescent male is reported. The
      clinical presentation was one of painless parotid swelling of 3 years duration
      with marked weight loss and underlying metabolic alkalosis. The diagnostic
      significance of parotid salivary gland swellings is discussed.

PMID- 8140017
TI  - Warfarin treatment and migraine.
AB  - A patient suffering from migraine, whose symptoms were abolished by warfarin
      therapy, is reported. Warfarin was prescribed for deep vein thrombosis and the
      frequency of the patient's headache improved remarkably during the anticoagulant
      therapy. Because of the unusual nature of the response to anticoagulant therapy,
      warfarin was reintroduced on a double blind (versus placebo) basis and once again
      abolished the headaches.

PMID- 8140016
TI  - A patient with coexisting narcolepsy and morbid jealousy showing favourable
      response to fluoxetine.
AB  - A 37 year old Chinese man suffered from coexisting narcolepsy and morbid jealousy
      which were precipitated by head injury 5 years previously. Fluoxetine 20 mg/day
      reduced his narcoleptic symptoms and morbid jealousy but not his sleepiness. On
      defaulting treatment, the patient's symptoms and marital problem recurred. A
      common central serotonin disturbance might be involved in mediating the sleep
      disorder and associated psychopathology.

PMID- 8140018
TI  - Hypokalaemic periodic paralysis in a thyrotoxic Polynesian.
AB  - Hypokalaemic periodic paralysis in a thyrotoxic Polynesian is described. The
      possible pathophysiology is discussed. Though common in Orientals, this condition
      is uncommon in Caucasians and has not been described before in a Polynesian.

PMID- 8140019
TI  - Pulmonary hypertension associated with non-cirrhotic portal hypertension in
      systemic lupus erythematosus.
AB  - A case of non-cirrhotic portal hypertension in a patient with systemic lupus
      erythematosus, the first of our knowledge, is described. Severe pulmonary
      hypertension was associated with the portal hypertension and with markers of
      active auto-immunity. Pulmonary hypertension has not previously been associated
      with non-cirrhotic portal hypertension. The coexistence of vasculopathy of the
      portal and pulmonary vascular beds in this patient with active autoimmunity
      supports the postulate that portal-pulmonary hypertension may be immunologically
      mediated.

PMID- 8140020
TI  - Hyperosmolar non-ketotic diabetic coma and rhabdomyolysis.
AB  - Rhabdomyolysis is a rare but potentially fatal complication of hyperosmolar
      states. We report a case of severe hyperosmolar non-ketotic diabetic coma causing
      rhabdomyolysis in a young man. Despite very high levels of creatine kinase there
      was no detectable myoglobinuria. Creatine kinase estimation should be a standard
      investigation in all patients presenting with a hyperosmolar state.

PMID- 8140021
TI  - Successful treatment of Pseudomonas paucimobilis haemodialysis catheter-related
      sepsis without catheter removal.
AB  - Infection is the most common complication of long-term central venous access
      lines. We report a case of central venous haemodialysis catheter infection with
      Pseudomonas paucimobilis, successfully treated by prolonged antibiotic
      administration without catheter removal. The implications are discussed.

PMID- 8140022
TI  - Tracheoesophageal fistula as the presenting manifestation of Hodgkin's lymphoma.
AB  - We present a patient with tracheoesophageal fistula as the initial manifestation
      of Hodgkin's disease with oesophageal involvement. To our knowledge, this has not
      been previously reported. The diagnosis of Hodgkin's lymphoma was made at
      autopsy.

PMID- 8140023
TI  - Treatment of the critically ischaemic lower limb.
AB  - Medical therapy of PAOD is only indicated in patients unsuitable for vascular
      reconstruction or angioplasty. The approach includes early detection of subjects
      at risk, avoidance of known risk factors, and appropriate management of diseases
      such as diabetes and hypertension. Vasodilators are of little use orally, though
      some drugs may have a part to play for short-term management and iloprost should
      be considered for patients unsuitable for revascularization. The ankle systolic
      or toe pressure should be used as a measure of disease and, if reduced,
      arteriography should be performed. This should not be limited to those thought
      fit for major surgery, as angioplasty or thrombolytic therapy may be appropriate,
      and aortoiliac disease may be treated by extra-anatomic bypass if not suitable
      for major surgery. Arterial reconstruction is associated with a reduction in both
      mortality and amputation, and should be attempted if a greater than 25% chance of
      limb salvage could be expected.

PMID- 8140024
TI  - Persistent monoarthritis and occult coeliac disease.
AB  - Arthritis is a recognized complication of untreated coeliac disease. Symptoms and
      signs usually respond to the institution of a gluten-free diet. We report a case
      of occult coeliac disease presenting as a monoarthritis. Severe and progressive
      erosive damage has occurred in his talo-navicular joint despite a response to the
      institution of a gluten-free diet.

PMID- 8140025
TI  - Right-sided endocarditis in the non-drug addict.

PMID- 8140026
TI  - Dystonia--a rare manifestation of carbamazepine toxicity.

PMID- 8140027
TI  - Streptokinase-induced jaundice.

PMID- 8140028
TI  - Massive rectal bleeding due to ileocaecal tuberculosis (conservative approach)

PMID- 8140029
TI  - Bradycardia associated with fluoxetine in an elderly patient with sick sinus
      syndrome.

PMID- 8140030
TI  - Rational experimental design and data analysis for ligand binding studies:
      tricks, tips and pitfalls.

PMID- 8140031
TI  - Influence of pregnancy on blood-brain barrier integrity during seizures in rats.
AB  - The effect of pregnancy on blood-brain barrier permeability was investigated
      during bicuculline-induced seizure in Wistar rats, using Evans-blue as a tracer.
      The experiments were carried out with two methods to investigate the integrity of
      the blood-brain barrier, i.e. Evans-blue albumin extravasation was determined as
      a macroscopical finding. A quantitative estimation with a spectrophotometer using
      homogenized brain to release the dye was performed to evaluate the macroscopical
      findings in a separate group of animals. During convulsions the mean arterial
      blood pressure increased in both pregnant and nonpregnant rats. The extravasation
      of Evans-blue was more pronounced in the nonpregnant rats. Mean values for Evans
      blue dye were found to be 0.29 +/- 0.07 mg% whole brain in nonpregnant control
      female rats and 0.30 +/- 0.09 mg% whole brain in pregnant rats. This difference
      was not significant (P > 0.05). Mean values for Evans-blue dye were 1.02 +/- 0.30
      mg% whole brain in nonpregnant female rats, and 0.60 +/- 0.12 mg% in the pregnant
      rats during bicuculline-induced seizures. This difference was significant (P <
      0.01). The severe protein leakage was seen in the thalamus, midcaudate,
      hypothalamus and mesencephalon bilaterally in the nonpregnant rats. However, in
      pregnant rats, Evans-blue leakage was similar to that of female rats except that
      the intensity of blood-brain barrier breakdown was less after convulsion.

PMID- 8140032
TI  - Vigabatrin as an anticonvulsant against pentylenetetrazol seizures.
AB  - The anticonvulsant effects of gamma vinyl GABA (GVG) were investigated against
      pentylenetetrazol (PTZ) seizures, while sodium valproate (VP) was used as
      positive control. At 1000 and 1500 mg kg-1 GVG was found to decrease seizure
      intensity either in 4 or 24 h, as effectively as VP. At 2000 mg kg-1 GVG was
      found to be almost ineffective. At both doses and both time spans of drug action,
      seizure latency was prolonged, compared to controls and VP group.

PMID- 8140033
TI  - Phytochemical screening and molluscicidal potency of some Zairean medicinal
      plants.
AB  - A total number of 48 plants used in the Zairean pharmacopoeia were tested against
      molluscan intermediate hosts of schistosomiasis and fascioliasis. Aqueous and
      ethanolic extracts from five plants: Maesa lanceolata, Chenopodium ugandae,
      Asparagus racemosus, Phyllanthus nummulariifolius and Crinum zeylanicum,
      exhibited high mortality rate (100%) against Biomphalaria pfeifferi and Lymnaea
      natalensis. Their LC50 was respectively 0.1, 5, 5, 10 and 50 mg ml-1 for B.
      pfeifferi and 0.5, 5, 1, 10 and 10 mg ml-1 for L. natalensis. The activities are
      attributed to the presence of terpenoids, steroids and saponins in the plant
      extracts. Except for the extracts from Ch. ugandae however, the plants have shown
      toxic effect on fishes and aquatic insects.

PMID- 8140034
TI  - Age-dependent modifications of the role of prostanoids in cardiac preparations
      from normotensive and hypertensive rats.
AB  - The cardiac response to field stimulation of adrenergic nerve terminals in
      isolated atrial preparations from adult (6-month-old) normotensive Wistar Kyoto
      (WKY) and spontaneously hypertensive (SH) rats was enhanced in comparison to that
      observed in the atrial tissue of young (2-month-old) animals of both strains; the
      increase in the sympathetic response was significantly higher in preparations
      from SHR than in those from age-matched WKY rats. The sensitivity of cardiac
      adrenergic neurotransmission to the prejunctional inhibitory effects exerted by
      exogenously administered prostaglandin E2 (0.1 nM-1 microM) and iloprost (0.1-10
      microM) did not show any strain-dependent difference in preparations from both
      young and adult rats. Moreover, acetylsalicylic acid (500 microM) induced a
      similar degree of potentiation of the response to sympathetic stimulation in
      atrial tissues of young WKY and SH animals; however, the effect of the cyclo
      oxygenase inhibitor was completely missing in preparations from adult rats of
      both strains. Finally, arachidonic acid (10 microM) inhibited the adrenergic
      response to a greater extent in preparations from young and adult SH rats than in
      those from age-matched normotensive rats. The results of the study indicate that,
      at least in cardiac preparations, changes in the modulatory role of endogenous
      prostaglandins occur as age-dependent processes and, therefore, may not be
      indicative of possible differences in the role of prostaglandins between
      hypertensive and normotensive animals. The possible significance of the
      dissimilar response to arachidonic acid, detected as the only difference between
      preparations from SH and WKY rats, is discussed.

PMID- 8140035
TI  - MacELLIPSE, a graphical aid to the problem of the joint confidence region: a
      practical example for ligand binding experiments.
AB  - The analysis of receptor binding experiments involving saturation or displacement
      curves may represent a problem when data are obtained from a number of
      experimental groups characterized by different tissues or different treatments.
      The conceptual difficulty of comparing such binding parameters and the complexity
      in graphically representing many curves is often overcome using tables and
      statistical tests for uncorrelated parameters. These, however, might be
      misleading. In fact, computing parameters using a nonlinear least squares (NLLS)
      technique may yield a significant covariance or correlation in the parameter
      estimates. In the present paper we suggest a practical method for comparing
      curves from different experimental groups using the LIGAND program and present
      the program MacELLIPSE that permits the graphical representation of the binding
      results together with the correlation existing between the estimated parameters.

PMID- 8140036
TI  - Effect of a bis(benzyl)polyamine analogue, and DL-alpha-difluoromethylornithine
      on parasite suppression and cellular polyamine levels in golden hamster during
      Leishmania donovani infection.
AB  - We examined the antileishmanial activity of DL-alpha-difluoromethylornithine
      (DFMO) and a bis(benzyl)polyamine analogue (MDL 27695; N,N'-bis (3-[(phenyl
      methyl)amino] propyl) 1,7-diaminoheptane) in L. donovani infected golden
      hamsters. DFMO, an enzyme activated irreversible inhibitor of ornithine
      decarboxylase, the rate limiting enzyme in polyamine biosynthesis, has potent
      antileishmanial activity. When given as a 2% solution in drinking water 2 days
      after infection and continued for 4 days, it suppressed liver parasites by 90%
      and spleen parasites by 99%. Liver parasites were suppressed by 50% and spleen
      parasites by 77% in L. donovani infected hamsters when treated three times per
      day for 4 days with a total dose of 60 mg kg-1 body weight of MDL 27695. The
      polyamine content of the liver and spleen of hamsters was determined after 8 days
      of L. donovani infection and also after treatment with these drugs. Putrescine
      and spermidine levels increased significantly in both liver and spleen after
      Leishmania infection of golden hamsters. Treatment with drugs that inhibit the
      growth of Leishmania mastigotes in the liver and spleen of golden hamsters also
      reduced polyamine levels of previously infected golden hamsters. There is a close
      correlation between the therapeutic activity of the drugs and the polyamine
      content.

PMID- 8140037
TI  - Synthesis of prostaglandin E2 in rat liver.
AB  - We have investigated whether rat liver microsomes can release prostaglandins and
      determined the 'optimal conditions' for the in vitro synthesis of PGE2. We also
      studied the effect of the oral administration of indomethacin, piroxicam and
      ibuprofen on PGE2 release ex vivo. The drugs were administered to animals at high
      doses for one or three consecutive days and the animals were killed 24 h after
      the first or the third administration. The increased PGE2 synthesis observed for
      indomethacin and piroxicam (animals treated for three consecutive days) could be
      explained by the depression of cytochrome P-450 observed in the same animals.
      Cytochrome P-450 could modulate the activity of eicosanoids derived from
      cyclooxygenase. Moreover the different inhibition of PG synthesis exhibited by
      these drugs could lead to a different rise in concentration of arachidonic acid
      in microsome membranes and contribute to an increased PGE2 synthesis.

PMID- 8140038
TI  - Interaction between drugs and pressure-sensitive adhesives in transdermal
      therapeutic systems.
AB  - Release experiments with four drugs using representative pressure-sensitive
      adhesive (PSA) matrices were performed at 37 degrees C, and drug-PSA polymer
      interaction was determined by the Williams, Landel, and Ferry (WLF) equation. Two
      acrylic-type [2-ethylhexylacrylate and acrylic acid copolymer (2EHA/AA) or
      acrylamide copolymer (2EHA/AAm)], one rubber-type (a mixture of high and low
      molecular weight polyisobutylene), and one silicone-type PSA were used, and
      dipropylphthalate (PP), aminopyrine (AMP), ketoprofen (KP), and lidocaine (LC)
      were selected as model drugs because of their molecular size and functional
      groups. PSA containing acrylic acid (2EHA/AA) strongly interacted with the amide
      LC, with the tertiary amine AMP, and with the carboxylic acid KP; PSA-containing
      acrylamide (2EHA/AAm), however, did not interact with LC or AMP, although it
      markedly interacted with KP. The rubber-type and silicone-type PSAs, composed of
      no or only a few polar functional groups, did not interact with any of the drugs
      used in this experiment. Therefore, the diffusion coefficient of the drugs
      through PSA was influenced by the drug-PSA polymer interaction, and the extent of
      this interaction can be estimated by the relationship between the drug
      concentrations in the PSA and their diffusion coefficients.

PMID- 8140039
TI  - Preparation, characterization, and pharmaceutical application of linear dextrins.
      III. Drug release from fatty suppository bases containing amylodextrin.
AB  - Drug release from fatty suppository bases containing a solid dispersion of
      diazepam with amylodextrin or a complex of prednisolone with amylodextrin was
      analyzed in a flow-through model. Being present as a suspension in the fatty
      base, particles of complex or solid dispersion are transported to the lipid-water
      interface by sedimentation. After entering the aqueous phase they partially
      dissolve. The suppositories showed increased drug release compared with the
      corresponding suppositories containing drug only. Because of the partial
      solubility of amylodextrin, drug release was lower than the release from drug
      cyclodextrin complexes. Use of the soluble fraction of amylodextrin for both the
      solid dispersion and the complex further enhanced drug release, but it was still
      below that of drug-cyclodextrin complexes.

PMID- 8140040
TI  - An organic acid-induced sigmoidal release system for oral controlled-release
      preparations.
AB  - To achieve time-controlled or site-specific drug delivery in the gastrointestinal
      tract, a sigmoidal release system (SRS) was developed, which achieved a prolonged
      lag time, followed by rapid release. The theophylline beads with a thick Eudragit
      RS film coating showed very low drug release in water, whereas the release rate
      increased considerably in organic acid solutions. A hydration study of Eudragit
      RS films suggested that the increase in drug release was attributable to
      structural changes of the film induced by polymer-acid interactions. When
      succinic acid was incorporated into the core of Eudragit RS-coated theophylline
      beads, the drug release profile showed a typical sigmoidal pattern. SRS beads
      containing acetaminophen were also prepared by the same technique. Again, a
      sigmoidal release pattern was observed in which the lag time was prolonged with
      an increase in the coating level, whereas the drug release rate thereafter was
      almost constant irrespective of the coating level. Acetaminophen-containing SRS
      beads with different coating thickness were orally administered to beagle dogs.
      The drug plasma concentration curves showed lag periods similar to the in vitro
      lag time.

PMID- 8140041
TI  - Bioavailability of flumequine after semisimultaneous administration to veal
      calves.
AB  - The absolute bioavailability of flumequine after semisimultaneous intramuscular
      administration as a water-based suspension to veal calves was 92 +/- 14%. The
      semisimultaneous experimental design provided a reliable determination of
      absorption rate and demonstrated flip-flop pharmacokinetics. No period or
      sequence effects were detected. Calculated elimination rate, clearance, and
      volume of distribution after intravenous administration were comparable to values
      obtained from traditional design studies. The semisimultaneous experimental
      design proved to be valuable for the assessment of bioavailability and
      pharmacokinetics of drugs in food-producing animals while preventing violation of
      basic clearance assumptions.

PMID- 8140042
TI  - Feasibility study on spray-drying protein pharmaceuticals: recombinant human
      growth hormone and tissue-type plasminogen activator.
AB  - The feasibility of spray-drying solutions of recombinant methionyl human growth
      hormone (hGH) and tissue-type plasminogen activator (t-PA) was investigated. hGH
      was formulated in a mannitol phosphate buffer and t-PA was used in an arginine
      phosphate formulation containing 0.004% (w/v) polysorbate 80. Using filtered air
      (90-150 degrees C) as the drying medium, hGH could be dried to a residual
      moisture content of < or = 4%. However, approximately 25% of the protein was
      degraded during the processing. Results of atomization studies suggest that
      surface denaturation at the air-liquid interface of the droplets in the spray
      plays a major role in the degradation of the protein. The addition of 0.1% (w/v)
      polysorbate 20 into the hGH formulation reduced the formation of soluble and
      insoluble aggregates by approximately 90% during atomization. During spray-drying
      the addition of 0.1% (w/v) polysorbate 20 reduced the formation of soluble and
      insoluble aggregates by approximately 70 and 85%, respectively. In contrast, t-PA
      remained intact upon atomization. Depending on the spray-drying conditions,
      product powders with a residual moisture content between 5 and 8% were obtained.
      No oxidation, aggregation, or denaturation occurred in the protein under several
      operation conditions. Overall, this study demonstrates that it is feasible to
      spray-dry t-PA in the current marketed formulation.

PMID- 8140043
TI  - Biodistribution of mixed fluorocarbon-hydrocarbon dowel molecules used as
      stabilizers of fluorocarbon emulsions: a quantitative study by fluorine nuclear
      magnetic resonance (NMR).
AB  - 19F NMR spectroscopy was used to determine quantitatively the organ distribution
      and organ retention time in rats of the mixed fluorocarbon-hydrocarbon dowel
      molecule C6F13CH = CHC10H21 (F6H10E), which stabilizes highly concentrated
      injectable fluorocarbon emulsions destined for in vivo oxygen transport and
      delivery. The only fluorine resonances detected in the 19F NMR spectra of the
      organs analyzed were those of the F6H10E dowel itself, indicating that
      metabolites, if present, have very low concentrations (< 10(-4) M, limit of our
      assay). The F6H10E content in the liver peaked 1 day after administration (7 days
      for the spleen). At a dose of 3.6 g/kg body weight, the half-life of F6H10E in
      the liver was 25 +/- 5 days.

PMID- 8140044
TI  - Validation of a variable direction hysteresis minimization pharmacodynamic
      approach: cardiovascular effects of alfentanil.
AB  - An important goal in therapeutics is the quantitative prediction of drug effects.
      Although several comprehensive pharmacodynamic models have been proposed,
      relatively few of these have attempted to assess objectively the application of
      the models to predict pharmacologic responses. A variable-direction hysteresis
      minimization approach was proposed recently that allowed the pharmacodynamics of
      drugs to be modeled using information about drug input. The application and
      validation of this approach are demonstrated using the pharmacodynamic effect of
      alfentanil, a short-acting narcotic analgesic agent, in New Zealand White
      rabbits. A parameter is proposed to assess the ability of the pharmacodynamic
      model to predict responses.

PMID- 8140045
TI  - Disposition of glycosidase inhibitors in the isolated perfused rat liver:
      hepatobiliary and subcellular concentration gradients of 1-deoxymannojirimycin
      and N-methyl-1-deoxynojirimycin.
AB  - The hepatic disposition of two glycosidase inhibitors was studied in the isolated
      perfused rat liver and after subcellular fractionation. The mannosidase inhibitor
      1-deoxymannojirimycin (dMM) and the glucosidase inhibitor N-methyl-1
      deoxynojirimycin (MedNM) exhibited minimal binding to albumin and reached liver
      concentrations that approximately equaled their medium concentrations, after 30
      min (MedNM) or 90 min (dMM). Within 2 hr 0.5% of the dose of MedNM and 2.9% of
      dMM were excreted in bile. No metabolites were found for MedNM, whereas minor
      (bio)degradation was inferred for dMM. After subcellular fractionation, dMM and
      MedNM were found predominantly in the cytosolic fraction. Compared to the other
      particulate fractions, MedNM was elevated in the microsomal fraction, and both
      compounds were slightly enriched in the lysosomal fraction. We conclude that dMM
      and MedNM will likely inhibit liver enzymes when sufficiently high plasma levels
      are reached.

PMID- 8140046
TI  - Influence of a fat-rich meal on the pharmacokinetics of a new oral formulation of
      cyclosporine in a crossover comparison with the market formulation.
AB  - The influence of a fat-rich meal on the pharmacokinetics of cyclosporine from a
      new oral formulation (Sandimmune Neoral) was compared in a randomized, four-way
      crossover study to the currently marketed formulation (Sandimmune) in 24 healthy
      male volunteers. Single oral doses of 300 mg Sandimmune and 180 mg Sandimmune
      Neoral were each administered once under fasting conditions and once 30 min after
      starting a high-fat meal. Serial blood samples were obtained over a 48-hr period
      after each administration, and whole-blood cyclosporine concentrations were
      determined by a specific monoclonal radioimmunoassay method. Food had a marked
      effect on cyclosporine absorption from Sandimmune manifested by a nearly doubled
      time to reach the peak concentration and a 37% increase in the area under the
      curve. This was associated with significant elevations in subsequent whole-blood
      cyclosporine concentrations compared to the fasting administration. For
      Sandimmune Neoral the influence was less pronounced. The maximum concentration
      was decreased by 26%, without a relevant change in the time to reach the peak;
      the area under the curve showed a slight reduction of 15%. The relatively minor
      influence of a fat-rich meal on the absorption of cyclosporine from Sandimmune
      Neoral is advantageous when individualizing a dosage regimen under clinical and
      outpatient administration conditions.

PMID- 8140047
TI  - Comparison of the pharmacokinetics of an ondansetron solution (8 mg) when
      administered intravenously, orally, to the colon, and to the rectum.
AB  - Ondansetron, an antagonist of the serotonin type 3 (5-HT3) receptor, is indicated
      for the treatment of chemotherapy-induced emesis. This study compares the
      pharmacokinetics, especially the bioavailability, of an ondansetron 8-mg solution
      when administered intravenously, orally, to the colon via nasogastric intubation,
      and to the rectum using a retention enema. Six healthy, male volunteers received
      ondansetron infused into the colon during the first treatment period. These
      subjects then received the remaining three treatments in random order, with a
      minimum 1-week washout period between treatments. Serial plasma samples were
      obtained for up to 24 hr after dosing in each treatment period. Absolute
      bioavailability after the oral dosing, colonic infusion, and rectal
      administration averaged 71 +/- 14, 74 +/- 26, and 58 +/- 18%, respectively. These
      values were not significantly different (P > 0.05). Values of Tmax and Cmax were
      also not significantly different among the nonparenteral routes. Mean absorption
      half-lives were 0.66, 1.1, and 0.75 hr after the oral, colonic, and rectal
      administrations, respectively. These results indicate that ondansetron is well
      absorbed in the intestinal segments studied including the upper small intestine,
      the colon, and the rectum and that sustained-release and suppository formulations
      of ondansetron are feasible.

PMID- 8140048
TI  - Pharmacokinetic analysis of in vivo metabolism of amino acid or dipeptide
      conjugates of salicylic acid in rabbit intestinal microorganisms.
AB  - We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine,
      glutamic acid, methionine, and tyrosine) or SA-dipeptide (glycylglycine)
      conjugates in rabbits, by using a model that takes into account the metabolism of
      prodrug to SA by intestinal microorganisms and, also, by model-independent
      analysis. The blood concentration profiles of these prodrugs and released SA
      following intracecal and oral administration to rabbits were obtained previously
      (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299, 1992; Chem. Pharm. Bull.,
      40, 2164-2168, 1992; Int. J. Pharm., 87, 59-66, 1992; J. Pharm. Pharmacol., 44,
      713-716, 1992). First, the overall in vivo behavior was evaluated by statistical
      moment analysis. Next, the blood concentration profiles of prodrug and SA
      following intracecal and oral administration were simultaneously fitted to the
      above model. In general, good agreement was observed between fitted lines and
      experimental data for every prodrug, suggesting the validity of this model. The
      obtained parameters characterized the difference in the rate of metabolism and
      absorption among the prodrugs. Lower absorbability and enhanced hydrolysis rate
      of the prodrug lead to prolonged blood concentration of SA.

PMID- 8140049
TI  - Epimerization and hydrolysis of dalvastatin, a new hydroxymethylglutaryl coenzyme
      A (HMG-CoA) reductase inhibitor.
AB  - In aqueous solutions, dalvastatin (1) undergoes epimerization as well as
      hydrolysis. The transformation of the drug was studied as a function of pH at 25
      degrees C in aqueous solutions containing 20% acetonitrile. At all pH values,
      first-order plots for the conversion are biphasic, indicating rapid equilibration
      of 1 with its epimer (2) and slower hydrolysis of 1 to the corresponding beta
      hydroxy acid (3). Apparent first-order rate constants for the biexponential
      equation are given as a function of pH. The alkyl-oxygen cleavage of the lactone
      ring results in the epimerization of 1 to 2, whereas the acyl-oxygen cleavage
      results in the hydrolysis of 1 to 3. The epimerization is an SN1 reaction
      reaching an equilibrium of [1]eq/[2]eq = 1.27. The epimerization rate is
      increased with an increase in the water content of the solvent. The hydrolysis of
      1 to 3 is acid and base catalyzed. The hydrolysis is reversible in acidic media
      and irreversible in neutral and basic media. At pH values greater than 9, the
      hydrolysis reaction proceeds more rapidly than the epimerization.

PMID- 8140050
TI  - Psychometric evaluation of measures of organizational commitment and intention to
      quit among pharmaceutical scientists.
AB  - This study utilized different statistical techniques to evaluate the reliability
      (internal consistency) and the discriminant validity of the most widely used
      measures of organizational commitment and intention to quit (the employing
      organization). Data were obtained from a national mail survey of members of the
      American Association of Pharmaceutical Scientists (AAPS) working in the
      pharmaceutical industry. Both instruments had high Cronbach alpha values in this
      sample of pharmaceutical scientists. There was a substantial correlation between
      the scale designed to measure organizational commitment and that for intention to
      quit. Factor analysis revealed that there was only one common factor underlying
      the 20 items that were originally designed to measure two distinct constructs.
      The findings in this study suggested that the most widely used instruments
      designed to measure organizational commitment and intention to quit may be
      actually measuring one construct, or the theoretical constructs named as
      organizational commitment and intention to quit may not be empirically distinct.

PMID- 8140051
TI  - Immunopotentiation and delivery systems for antigens for single-step
      immunization: recent trends and progress.
AB  - The use of adjuvants for immunopotentiation has been investigated since the 1920s
      and a number of comprehensive reviews and monographs have been published on this
      subject. A recent trend in immunopotentiation has been the use of delivery
      systems which allow for sustained or controlled release of antigens and which
      induce prolonged immunity following a single dose. This concept has been termed
      either single-step or single-shot immunization. The delivery system has been
      modulated to potentiate the immune response either by delivering the antigen (and
      perhaps an adjuvant or adjuvants) either over a prolonged period of time or in a
      predetermined sequence or by incorporating substances with immunoadjuvant
      properties (e.g., lecithin and certain biodegradable polymers) as carriers within
      the delivery system. This Review focuses on the progress made in the design of
      delivery systems for immunopotentiation. Particular emphasis is given to delivery
      systems designed to achieve single-step immunization.

PMID- 8140052
TI  - Moisture-induced aggregation of lyophilized insulin.
AB  - A critical problem in the storage and delivery of pharmaceutical proteins is
      aggregation in the solid state induced by elevated temperature and moisture.
      These conditions are particularly relevant for studies of protein stability
      during accelerated storage or for proteins loaded in polymeric delivery devices
      in vivo. In the present investigation, we have found that, when exposed to an
      environment simulating these conditions, lyophilized insulin undergoes both
      covalent and noncovalent aggregation. The covalent process has been elucidated to
      be intermolecular thiol-catalyzed disulfide interchange following beta
      elimination of an intact disulfide bridge in the insulin molecule. This process
      is accelerated by increasing the temperature and water content of the insulin
      powder or by performing lyophilization and/or dissolution of insulin in alkaline
      media. The aggregation can be ameliorated by the presence of Cu2+, which
      presumably catalyzes the oxidization of free thiols. The water sorption isotherm
      for insulin reveals that the extent of aggregation directly correlates with the
      water uptake by the lyophilized insulin powder, thus pointing to the critical
      role of protein conformational mobility in the aggregation process.

PMID- 8140053
TI  - Transcellular transport of benzoic acid across Caco-2 cells by a pH-dependent and
      carrier-mediated transport mechanism.
AB  - The pH-dependent transcellular transport of [14C]benzoic acid across a Caco-2
      cell monolayer is shown to be mediated by a monocarboxylic acid-specific carrier
      mediated transport system, localized on the apical membrane. Evidence for the
      carrier-mediated transport of benzoic acid includes (a) the significant
      temperature and concentration dependence, (b) the metabolic energy dependence,
      (c) the inhibition by unlabeled benzoic acid and other monocarboxylic acids, (d)
      countertransport effects on the uptake of [14C]benzoic acid, and (e) effects of a
      proteinase (papain) and amino acid-modifying reagents. Furthermore, since
      carbonylcyanide p-trifluoromethoxyphenylhydrazone and nigericin significantly
      inhibited the transport of [14C]benzoic acid, the direct driving force for
      benzoic acid transport is suggested to be the inwardly directed proton gradient.
      From these results, together with previous observations using intestinal brush
      border membrane vesicles, the pH dependence of the transcellular transport of
      certain organic weak acids across Caco-2 cells is considered to result mainly
      from a proton gradient-dependent, carrier-mediated transport mechanism, rather
      than passive diffusion according to the pH-partition theory.

PMID- 8140054
TI  - Intracellular visualization of ampicillin-loaded nanoparticles in peritoneal
      macrophages infected in vitro with Salmonella typhimurium.
AB  - Intracellular targeting of ampicillin by means of polyisohexylcyanoacrylate
      (PIHCA) nanoparticles was studied in murine peritoneal macrophages infected with
      Salmonella typhimurium. The intracellular distribution of actively endocytosed
      nanoparticles was visualized by transmission electron microscopy and confocal
      microscopy. Nanoparticles were either isolated or closely associated with
      bacteria within phagosomes or phagolysosomes. Thus the potential of ampicillin
      loaded nanoparticles in targeting of intracellular bacteria is demonstrated.
      Consequently, ampicillin, which usually penetrates into cells at a low level, is
      directly carried in, when loaded on nanoparticles, and brought into contact with
      intracellular bacteria.

PMID- 8140055
TI  - Conformational analysis, molecular modeling, and quantitative structure-activity
      relationship studies of agents for the inhibition of astrocytic chloride
      transport.
AB  - Molecular modeling studies were carried out on a series of 1-oxoisoindolines
      which are pharmacologically active as inhibitors of astrocytic chloride
      transport. Conformational analysis revealed that the halogen substituent exerted
      a pronounced steric directing effect on the acid side chain. The 4-substituted
      analogs apparently provided for the best spatial arrangement of pharamacophoric
      elements of the molecules. Conventional quantitative structure-activity
      relationship (QSAR) studies using lipophilic and dipole moment characteristics of
      the molecules as physical descriptor variables in the regression equation yielded
      a statistically significant model. Comparative molecular field analysis (CoMFA)
      was utilized as a three-dimensional QSAR technique to explore changes in the
      steric and electrostatic fields of the molecules that can account for differences
      in biological activity values. A highly predictive model was attained which
      supported the results from the qualitative and conventional quantitative
      structure-activity relationship analyses. These modeling techniques represent the
      evolutionary process by which structure-activity methods were employed to aid in
      the development of novel more potent inhibitors of astrocytic chloride transport.

PMID- 8140056
TI  - Measurement of glass transition temperatures of freeze-concentrated solutes by
      differential scanning calorimetry.
AB  - Thermal analysis of aqueous solutions in which the solute does not crystallize
      immediately upon freezing was carried out to define the effects of experimental
      parameters on thermograms in the glass transition region. The intensity of
      enthalpy relaxations in the glass transition region is related to both the rate
      of cooling and the rate of heating through the glass transition region--slow
      cooling or slow heating increases the extent of structural relaxation in the
      glassy state and increases the intensity of the endotherm. Plots of the logarithm
      of heating rate versus 1/Tg' are linear, and activation enthalpies for structural
      relaxation are in the range of 210-350 kJ/mol. For polymeric solutes, both the
      activation enthalpies for structural relaxation and the heat capacity change
      accompanying the glass transition increase with increasing molecular weight of
      the solute. Molecular weight dependence of the observed midpoint of the glass
      transition agrees with the Fox-Flory relationship. Results are compared and
      contrasted with glass transitions in solid polymers and with the glass transition
      of hyperquenched water. Practical implications for characterization of
      formulations intended for freeze-drying are discussed.

PMID- 8140057
TI  - Clearance mechanisms of atrial and brain natriuretic peptides in rats.
AB  - To assess clearance mechanisms of atrial and brain natriuretic peptides in the
      circulation, we examined the effects of a neutral endopeptidase (NEP) inhibitor
      and a clearance receptor ligand on plasma concentrations of the peptides in
      normal rats. Plasma concentrations of endogenous alpha-rat atrial natriuretic
      peptide (alpha-rANP) were not significantly elevated by intravenous infusion of a
      NEP inhibitor, phosphoramidon, but were elevated threefold by intravenous
      infusion of a clearance receptor ligand, des(Gln18-Gly22)-rANP(4-23)-NH2 [C-ANF(4
      23)]. On the other hand, the clearance of alpha-rANP given intravenously at the
      pharmacological dose, 600 pmol/min/kg for 2 min, was decreased to one-third by
      the administration of phosphoramidon, although the administration of C-ANF(4-23)
      did not significantly decrease the clearance. The clearance of rat brain
      natriuretic peptide (rBNP) given at 600 pmol/min/kg for 2 min was approximately
      38% lower than that of alpha-rANP. The effect of phosphoramidon on the clearance
      of rBNP was not significant and was similar to that of C-ANF(4-23). These results
      suggest that clearance receptor is involved in the clearance of the physiological
      levels of alpha-rANP and that NEP plays a major role in the clearance of a
      pharmacological dose of alpha-rANP, at which clearance receptors are thought to
      be saturated, and also indicate a pharmacokinetic difference between alpha-rANP
      and rBNP.

PMID- 8140058
TI  - Acid-catalyzed peptide bond hydrolysis of recombinant human interleukin 11.
AB  - Recombinant human interleukin 11 (rhIL-11) is a multispectrum cytokine that plays
      an important role in megakaryocytopoiesis and platelet production. Probing rhIL
      11 chemical reactivity in aqueous solution is an important initial step in
      developing a dosage form for rhIL-11 clinical trials. This report documents rhIL
      11 degradation kinetics at 50 degrees C in solutions adjusted to pH 3.0 to 9.5.
      Stressed samples were analyzed by reverse-phase HPLC and degradation product
      peaks were isolated for structural characterization. The results show maximal
      stability in the region pH 6.5 to 7.0. Degradation product identification shows
      that the major reaction pathway in acidic solution involves peptide cleavage at
      aspartate133-proline134. In alkaline solution, protein disappearance proceeds via
      nonspecific loss to container surfaces. Degradation products at alkaline pH have
      not been identified.

PMID- 8140059
TI  - Primary culture of rat gastric epithelial cells as an in vitro model to evaluate
      antiulcer agents.
AB  - Primary rat gastric cell cultures were investigated as an in vitro model for
      evaluating antiulcer agents. Following exposure to concentrations of up to 5
      mg/mL of an antiulcer agent sucralfate, an aluminum hydroxide complex of sucrose
      octasulfate, cultured cells were treated with either pH 3.5 medium or 3.5 mM
      indomethacin. Cytoprotection was evaluated by colony forming efficiency, neutral
      red uptake, and 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide
      (MTT) hydrolysis. By each measure, and depending on damaging agent, 2 and 5 mg/mL
      sucralfate provided partial (50% of untreated control) to near-complete (90% of
      untreated control) cytoprotection, respectively. Aluminum hydroxide also provided
      partial (55% of untreated control) to near-complete (more than 90% of untreated
      control) cytoprotection at 2 and 5 mg/mL, respectively, for the pH 3.5 medium
      induced damage. Over a concentration range of 0.05 to 5 mg/mL, the potassium salt
      of sucrose octasulfate, KSOS, stimulated cell growth up to 40-60% over untreated
      controls but had little or no cytoprotective action in the presence of either 3.5
      mM indomethacin or pH 3.5 medium. Overall results suggested that sucralfate may
      have at least two roles in influencing gastric epithelial cell function,
      cytoprotection and stimulation of cell growth in vitro. These observations serve
      as a basis for further study of in vitro models in evaluating the cytoprotective
      activity of antiulcer agents and their respective mechanisms of action.

PMID- 8140060
TI  - Effect of cyclodextrins on protein binding of drugs: the diflunisal/hydroxypropyl
      beta-cyclodextrin model case.
AB  - The binding of diflunisal to hydroxypropyl-beta-cyclodextrin (HP beta CD), bovine
      serum albumin (BSA), human serum albumin (HSA), normal human plasma, and mixed
      solutions of HP beta CD/protein was studied at 25 degrees C, pH 7.4, by
      potentiometry using an electrode selective to diflunisal. The experimental data
      for diflunisal/HP beta CD fit well to the 1:1 binding model. The binding of
      diflunisal with each of the studied proteins was compatible with a model having
      two independent classes of binding sites. The binding of diflunisal in mixed
      solutions HP beta CD/BSA, HP beta CD/HSA, and HP beta CD/plasma increased
      considerably when the HP beta CD concentration was increased. The binding
      behavior of the two biomolecules in the mixed solutions of HP beta CD/BSA or HP
      beta CD/HSA was described with an "additive" model formulated on the basis of the
      estimates of the binding parameters of diflunisal derived from the separate
      experiments with each one of the binders tested. The lower than theoretical
      binding observed in HP beta CD/plasma solutions was ascribed to the competitive
      displacement of diflunisal from the HP beta CD cavity by plasma cholesterol.

PMID- 8140061
TI  - Analysis of the combined effect of 1-menthol and ethanol as skin permeation
      enhancers based on a two-layer skin model.
AB  - The combined effects of 1-menthol and ethanol as a skin permeation enhancer were
      evaluated with two equations describing the permeability coefficient through full
      thickness skin (PFT) and the full-thickness skin/vehicle concentration ratio
      (CFT/CV) of drugs as a function of their octanol/vehicle partition coefficient
      (KOV). A two-layer model was applied for skin, which consists of a stratum
      corneum (SC) with lipid and porous pathways and a viable epidermis and dermis
      (ED). The two equations contain one variable (KOV) and nine coefficients, six of
      which (three diffusion coefficients, the porosity of the SC, and two terms of the
      linear free energy relationship) were considered different, dependent on the drug
      vehicle. In vitro permeation of four drugs (morphine hydrochloride, atenolol,
      nifedipine, and vinpocetine) was determined using excised hairless rat skin and
      four aqueous vehicles (water, 5% 1-menthol, 40% ethanol, and 5% 1-menthol-40%
      ethanol) to measure each PFT. Drug concentrations in full-thickness skin were
      also measured to obtain CFT/CV. A nonlinear least-squares method was employed to
      determine six coefficients using the two equations and experimentally obtained
      PFT and CFT/CV. The addition of 1-menthol to water and 40% ethanol increased the
      diffusion coefficient of drugs in lipid and pore pathways of SC, whereas the
      addition of ethanol to water and 5% 1-menthol increased the drug solubility in
      the vehicle, decreased the skin polarity, and increased the contribution of the
      pore pathway to whole-skin permeation.

PMID- 8140063
TI  - Prenatal diagnosis of congenital cytomegalovirus infection: false-negative
      amniocentesis at 20 weeks' gestation.
AB  - Cytomegalovirus (CMV) is the most common cause of congenital infection. Recent
      studies show amniocentesis to be a 100 per cent sensitive and 100 per cent
      specific predictor of congenital infection, and recommend that it be offered in
      the at-risk pregnancy. However, these publications have focused on pregnancies at
      or beyond 22 weeks' gestation. Here, we report a case of maternal CMV hepatitis
      at 7-8 weeks' gestation, in which culture and polymerase chain reaction testing
      for CMV in amniotic fluid at 20 weeks' gestation were negative, but the infant
      had a positive CMV urine culture shortly after delivery. Implications for the
      prenatal diagnosis of CMV infection are discussed.

PMID- 8140062
TI  - Fetal akinesia/hypokinesia sequence: prenatal diagnosis and intra-familial
      variability.
AB  - Intrauterine fetal movement plays a key role in normal embryonic and fetal
      development (Moessinger, 1983). When movement is absent or decreased, abnormal
      development takes place which can be appreciated in newborns and/or fetuses with
      the fetal akinesia/hypokinesia sequence. This sequence is caused by a number of
      heterogeneous entities which result in decreased fetal movements by the action of
      intrinsic or extrinsic factors. Prenatal diagnosis of the akinesia/hypokinesia
      sequence may be possible during the second trimester through the use of real-time
      ultrasonographic evaluation of fetal movement. We report a family with three
      consecutive affected pregnancies in which the prenatal presentation of this
      sequence varied. Based on the phenotypic findings of the three affected fetuses,
      we believe that although they superficially resemble those features found in the
      New-Laxova syndrome, they are probably affected with a distinctly different
      lethal form of akinesia/hypokinesia transmitted in an autosomal recessive
      fashion.

PMID- 8140064
TI  - DNA confirmation of congenital myotonic dystrophy in non-immune hydrops fetalis.
AB  - We report on the prenatal diagnosis of congenital myotonic dystrophy in a case of
      non-immune hydrops fetalis. DNA analysis of amniocytes revealed expansion of the
      trinucleotide (CTG) repeat within the myotonin PK gene, associated with myotonic
      dystrophy. The fetus was found to have approximately 1730 copies, while the
      normal population has between 5 and 27 copies, and minimally affected individuals
      have at least 50 copies.

PMID- 8140065
TI  - Transcervical CVS sample size: correlation with placental location, cytogenetic
      findings, and pregnancy outcome.
AB  - Data from 2907 transcervical CVS cases performed on singleton pregnancies were
      reviewed retrospectively and villus sample size was correlated with cytogenetic
      results, placental location, maternal age at the expected date of confinement
      (EDC), gestational age at the time of sampling, birth weight, gestational age at
      the time of delivery, and pregnancy outcome. No correlation was noted between
      villus sample size and maternal age, gestational age at sampling, gestational age
      at delivery, birth weight, or pregnancy outcome. An inverse correlation between
      villus sample size and percentage of abnormal cytogenetic findings was
      statistically significant (chi 2 = 8.53, p < 0.01). The percentage of small
      samples was greater when the placenta was anterior, lateral, or fundal than when
      the placenta was posterior.

PMID- 8140066
TI  - Prenatal diagnosis of neonatal alloimmune thrombocytopenia using an allele
      specific oligonucleotide probe.
AB  - The prediction of neonatal alloimmune thrombocytopenia (NAIT) in affected
      families is usually based on information about gene frequencies of the antigen
      systems involved, parental phenotyping, and fetal platelet counts. Recently the
      use of allele-specific oligonucleotide probe typing for PlA (HPA-1) antigens has
      been described to determine the risk of second or subsequent fetuses in families
      where one infant had the diagnosis of anti-PlA1 (HPA-1a)-mediated NAIT (McFarland
      et al., 1991a). This paper describes the first case in which the prenatal
      diagnosis of PlA (HPA-1) antigen status was accomplished using this technology on
      genomic DNA derived from chorionic villus tissue in the first trimester, and
      presents the implications of these findings for the clinical management of this
      disorder.

PMID- 8140067
TI  - Serum hCG assay: a method for detection of contamination of fetal blood samples.
AB  - Serum human chorionic gonadotrophin (hCG) can be assayed in specimens obtained by
      percutaneous fetal blood sampling to check for the absence of maternal blood or
      amniotic fluid contamination. In order to assess the accuracy of this approach,
      we measured serum hCG in 44 pure fetal blood samples obtained by intracardiac
      puncture. The mean fetal serum hCG concentration was 52 IU/l, and the ratio of
      maternal to fetal serum hCG concentration never exceeded 1.1 per cent, which
      represents the smallest contamination rate detectable by this method.

PMID- 8140068
TI  - Transverse limb reduction defects after chorion villus sampling: a retrospective
      cohort study. GIDEF--Gruppo Italiano Diagnosi Embrio-Fetali.
AB  - A retrospective cohort study was performed in five Italian obstetrical centres
      from 1984 to 1991 in order to verify the association between chorionic villus
      sampling (CVS) and transverse limb reduction defects (TLRDs). TLRD rates by
      period of gestation at CVS were calculated, and the study's results were compared
      with data from the general population. Of the 3430 pregnancies for which CVS was
      performed, 2759 had a known outcome. The overall rate for TLRDs was 1 in 1143 CVS
      pregnancies, four times higher than that of the general population in Italy (1 in
      4458). The rate of TLRDs was 2.9/1000 for CVS performed at 9 weeks' gestation and
      1.0/1000 for CVS at 10 weeks' gestation. A scalp defect was detected in a
      pregnancy in which CVS was performed at 10 weeks. A high proportion of
      pregnancies lost to follow-up and the poor quality of the data may have affected
      the results. Nevertheless, our results suggest an association between CVS carried
      out at less than 10 weeks' gestation and TLRDs which is consistent with the
      findings of other studies. CVS should not be prepared at less than 10 weeks'
      gestation until additional evidence is obtained.

PMID- 8140069
TI  - Prenatal confirmation of trisomy 12 mosaicism by fetal skin biopsy.
AB  - Trisomy 12 mosaicism diagnosed at 16 weeks' amniocentesis in a 42-year-old woman
      was not confirmed at 18 weeks' gestational age in amniotic fluid or fetal blood.
      Fetal skin biopsy performed at the same time did, however, allow the detection of
      trisomy 12 in 1 of 14 fibroblasts analysed. Fetal skin biopsy can be included
      within the diagnostic procedures to be performed when a level III mosaicism is
      found in the amniotic fluid.

PMID- 8140070
TI  - An unusual tricentric X chromosome detected prenatally.
AB  - We describe a female fetus with a de novo X chromosome rearrangement detected
      prenatally in both chorion villi and a pleural effusion. Chromosome painting
      showed the chromosome to be composed entirely of X chromosome material, while G
      banding indicated a duplication of X short arms, four copies of the proximal long
      arm, and deletion of the distal long arm of the X. C-banding showed the presence
      of one active and two inactive centromeres and X-inactivation studies
      demonstrated the tricentric chromosome to be late replicating in all cells
      examined. The origin of this complex de novo rearrangement appears to have
      involved two separate breakage events, the first leading to the production of a
      dicentric X chromosome and the second generating the tricentric X.

PMID- 8140071
TI  - Identical twins with trisomy 21 discordant for exomphalos.

PMID- 8140072
TI  - The association between 'faint-positive' amniotic fluid acetylcholinesterase and
      fetal malformations.
AB  - The finding of a 'faint-positive' acetylcholinesterase band in amniotic fluid
      samples of women at 15 weeks' gestation or above is associated with an increased
      risk of fetal abnormalities, most commonly gastroschisis. This finding warrants a
      targeted sonographic evaluation, in order to rule out significant fetal
      malformations.

PMID- 8140073
TI  - Heteroduplex detection: application to rapid prenatal diagnosis for a type of
      beta-thalassaemia most commonly found in south China.

PMID- 8140074
TI  - CVS and porencephaly.

PMID- 8140075
TI  - Erythromelalgic, thrombotic and haemorrhagic manifestations of thrombocythaemia.
AB  - OBJECTIVES: In order to document a relationship between platelet counts and
      clinical complication of thrombosis or bleeding in patients with
      myeloproliferative thrombocythaemia, 200 consecutive published cases of
      thrombocythaemia were reviewed for thrombotic or haemorrhagic manifestations and
      haematological findings at the time of the thrombohaemorrhagic complication.
      METHODS: Cases selected from the literature included all those complying with the
      diagnosis of thrombocythaemia as mandated by the Polycythemia Vera Study Group.
      One hundred consecutive cases of thrombocythaemia complicated by bleedings and
      one hundred consecutive cases of thrombocythaemia complicated by thrombosis were
      reviewed for clinical manifestations and haematological findings. RESULTS: In the
      reviewed cases of thrombocythaemia haemorrhagic complications (platelet count
      2016 +/- 1070 x 10(9)/1) occurred at significantly (p < 0.001) higher degrees of
      thrombocytosis than thrombotic complications (platelet count 1110 +/- 477 x
      10(9)/1). CONCLUSIONS: In the reviewed cases of thrombocythaemia arterial
      complications, especially erythromelalgia, can already be documented at platelet
      counts in excess of 400 x 10(9)/1, whereas bleeding complications usually occur
      at significantly higher degrees of thrombocytosis (> 1000 x 10(9)/1).

PMID- 8140076
TI  - Hypoglycaemia-induced ischaemic ECG changes.
AB  - A patient with an 8 year history of insulin-dependent diabetes mellitus was
      admitted to the emergency ward for hypoglycaemic coma (blood glucose 1.11
      mmol/l). The initial electrocardiogram revealed a junctional rhythm and major
      ischaemia with an ST depression of 6-7 mm. Sinus rhythm and normal repolarization
      were recovered 15 minutes after administration of 50% glucose. No evidence of
      myocardial infarction appeared during follow-up. Such hypoglycaemia-induced ECG
      changes have rarely been documented and no conclusive explanation has been put
      forward although altered balance between energy supply and demand in myocardial
      tissue has been suggested. Special care should be taken when administering
      hypoglycaemic agents to patients at risk for myocardial ischaemia.

PMID- 8140077
TI  - [Erythropoietin for autologous transfusion. Use in a case of severe anemia with
      allo-immunization].
AB  - In view of the transfusional risks of viral transmission (notably HIV),
      autologous transfusion is increasingly used; it is often the only possible type
      of transfusion. A 42-year-old woman with lupus erythematosus, chronic renal
      failure and triple cardiac valve disease demanding surgery was admitted for
      multifactorial severe anaemia. Treatment with erythropoietin (8000 units/day)
      iron replenishment, corticosteroids and polyvalent immunoglobulins was initiated.
      The patient was operated upon in April 1990. A preoperative cell-saver
      autotransfusion was performed during surgery. The postoperative period was
      uneventful. Homologous transfusion was not necessary. In this case where
      homologous transfusion was ruled out, erythropoiesis stimulated by erythropoietin
      enabled autotransfusion and cardiac surgery to be performed.

PMID- 8140078
TI  - [Hyperlipidemia during diabetes mellitus. Recent developments].
AB  - Patients with diabetes mellitus are at increased risk of coronary, cerebral, and
      peripheral vascular disease, and frequently have abnormal plasma lipid levels.
      Glycaemic control, environmental factors and inherent genetic potential may
      affect lipoprotein metabolism. Quantitative alterations in the concentrations of
      major lipids and lipoproteins have been extensively studied in both insulin
      dependent diabetes mellitus and non-insulin-dependent diabetes mellitus. However
      several recent findings indicate the possible presence of structural and
      functional abnormalities that may impair the lipid metabolism transport system in
      diabetic patients. These include glycation of several major or minor
      apolipoproteins, apo E phenotype frequency, free cholesterol or triglyceride
      enrichment of VLDL and LDL. Moreover lipoprotein (a) which is an independent risk
      factor for coronary heart disease may be increased in diabetic patients with poor
      glycaemic control or with microproteinuria. Patients with microalbuminuria or
      chronic renal failure show atherogenic changes of lipoprotein pattern. New
      epidemiological evidence indicates that hypertriglyceridaemia is an important
      predictor of coronary heart disease mortality in subjects with impaired glucose
      tolerance or diabetes. Postprandial lipaemia can increase the risk of
      cardiovascular disease potentially by low triglyceride metabolic capacity. The
      role of insulin must also be considered. Some lipoprotein abnormalities could be
      attributed to peripheral hyperinsulinaemia, insulin resistance or type of insulin
      infusion for insulin-dependent diabetes mellitus patients. In diabetes lipids and
      lipoproteins are potentially atherogenic although their concentrations may be
      strictly normal. The achievement of optimum lipid and lipoprotein levels as a
      goal of treatment for diabetic patients would reduce the current rates of
      morbidity and mortality from vascular disease.

PMID- 8140079
TI  - [Symptomatic hypercalcemia after vitamin D-thiazide diuretics combination. Two
      cases in elderly women].

PMID- 8140080
TI  - [Meningomyelitis in Rickettsia conorii infection].

PMID- 8140081
TI  - [Syndrome of hyperimmunoglobulinemia E in a HIV-1 seropositive patient. A new
      case].

PMID- 8140082
TI  - [Tick-borne encephalitis in central Europe: a rare cause of autochthonous meningo
      encephalo-myelitis].

PMID- 8140083
TI  - [Unilateral spontaneous hematoma of cystic lymphangioma of the adrenal gland in a
      pregnant woman].

PMID- 8140084
TI  - [Hepatotoxicity of antitubercular agents in children].

PMID- 8140085
TI  - [Psychotic disorders in Parkinson disease: value of clozapine].

PMID- 8140086
TI  - Finding your fold.

PMID- 8140087
TI  - A calmodulin-target peptide hybrid molecule with unique calcium-binding
      properties.
AB  - This paper describes the production and properties of a hybrid protein comprising
      the full length of the Xenopus laevis calmodulin (CaM) sequence, followed,
      through a glycylglycine linker, by the 26-residue CaM-binding region of myosin
      light-chain kinase (M13). This hybrid molecule appears to have high thermal
      stability (Tm > 75 degrees C in the presence of Ca2+) as well as unusual Ca(2+)
      binding properties: (i) a wide-range biphasic Ca(2+)-binding response (extending
      over pCa 4.8-7.4) and (ii) a high apparent binding constant (pCa50% = 6.3, a 10
      fold increase from that of wild-type CaM). NMR and CD data indicate that the CaM
      M13 hybrid molecule exists in equilibrium in an approximate 1:1 ratio between two
      major conformations, one of which is similar to the compact globular structure of
      the CaM-M13 complex [M.Ikura, G.M. Clore, A.M. Gronenborn, G. Zhu, C.B. Klee and
      A. Bax (1992) Science, 256, 632-638] and the other to the dumb-bell-like
      structure of the wild type CaM [Y.S. Babu, C.E. Bugg and W.J. Cook (1988) J. Mol.
      Biol., 204, 191-204]. The biphasic Ca(2+)-binding curve can be interpreted using
      a linear combination of two Hill binding curves with significantly different
      dissociation constants (2 x 10(-9) M and 8 x 10(-8) M), which can be attributed
      to the two conformations in equilibrium. The present study has opened an avenue
      to engineer proteins with higher Ca(2+)-binding affinities using the known CaM
      structures as a template.

PMID- 8140088
TI  - An internal cellulose-binding domain mediates adsorption of an engineered
      bifunctional xylanase/cellulase.
AB  - A chimeric xylanase/endoglucanase (XynCenA) with an internal cellulose-binding
      domain was constructed by fusing the Bacillus subtilis xyn gene fragment to the
      5'-end of the Cellulomonas fimi cenA. A polyhistidine-encoding sequence was also
      fused to the 5'-end of the xyn gene. The gene fusion was overexpressed in
      Escherichia coli and the fusion polypeptide purified from the cell extracts using
      the polyhistidine tail. The hybrid protein behaved like the parental
      endoglucanase or xylanase when assayed on a number of soluble and insoluble
      cellulosic substrates or xylans. The presence of two distinct active sites and
      the internal cellulose-binding domain did not significantly affect the hydrolysis
      of any of these substrates. However, the fusion protein exhibited a strong
      affinity for both microcrystalline cellulose (Avicel) and regenerated chitin.
      Like the parental endoglucanase, bound XynCenA could not be eluted from these
      polysaccharides with either low or high salt buffer or distilled water. More
      stringent conditions, such as 1% SDS or 8 M guanidinium hydrochloride, fully
      desorbed the protein. The fusion protein did not adsorb significantly to
      insoluble xylan.

PMID- 8140089
TI  - Cloning, expression and purification of a sarcoplasmic calcium-binding protein
      from the sandworm Nereis diversicolor via a fusion product with chloramphenicol
      acetyltransferase.
AB  - A gene coding for the Nereis sarcoplasmic calcium-binding protein (NSCP) was
      synthesized and expressed in Escherichia coli. The sequence of the gene was
      derived from the protein sequence by reverse translation. It possesses a number
      of unique, regularly spaced, restriction endonuclease cleavage sites to
      facilitate future site-directed mutagenesis. For the cloning strategy the gene
      sequence was divided into four parts. Three parts were cloned by ligation of
      hybridized oligomers and one part by inverse PCR. The protein was expressed as a
      fusion protein with the bacterial chloramphenicol acetyl-transferase (CAT), which
      could be easily purified by affinity chromatography. At the junction of the CAT
      and NSCP moieties a recognition site for the proteolytic enzyme factor Xa was
      built in. However, the distance between the moieties appeared to be crucial to
      warrant cleavage. A kinetic analysis showed that NSCP prepared from the sandworm
      and the one expressed by E. coli behaved in the same way. This system provides a
      basis for site-specific mutagenesis studies, in order to elucidate the molecular
      mechanism of cation binding and concomitant conformational changes.

PMID- 8140090
TI  - Secondary structure characterization of beta-lactamase inclusion bodies.
AB  - The secondary structure of proteins in E. coli inclusion bodies was investigated
      via Raman spectroscopy. Inclusion bodies were purified from cells expressing
      different forms of RTEM beta-lactamase and grown at either 37 or 42 degrees C.
      All of the solid phase inclusion body samples examined gave amide I band spectra
      that were perturbed from that of the native, purified protein in both solution
      and powder forms; secondary structure estimates indicated significant decreases
      in alpha-helix and increases in beta-sheet contents in the inclusion body
      samples. The structure estimates for inclusion bodies isolated from 37 degrees C
      cultures were similar, regardless of aggregate localization in the E. coli
      cytoplasmic or periplasmic spaces or beta-lactamase precursor content. Inclusion
      bodies obtained from 42 degrees C cells exhibited a further reduction of alpha
      helix and augmentation of beta-sheet contents relative to those from 37 degrees C
      cultures. These results are consistent with the paradigm for inclusion body
      formation via the self-association of intra-cellular folding intermediates having
      extensive secondary structure content. Further, the overall secondary structure
      content of inclusion bodies is not significantly affected by subcellular
      compartmentalization, but may be altered at increased temperatures.

PMID- 8140091
TI  - A novel search method for protein sequence--structure relations using property
      profiles.
AB  - In protein engineering and design it is very important that residues can be
      inspected in their specific environment. A standard relational database system
      cannot serve this purpose adequately because it cannot handle relations between
      individual residues. With SCAN3D we introduce a new database system for
      integrated sequence and structure analysis of proteins. It uses the relational
      paradigm wherever possible. Its main power, however, stems from the ability to
      retrieve stretches of consecutive residues with certain properties by comparing a
      property profile with all stretches of residues in the database, exploiting the
      ordered character of proteins. In doing so, it bypasses the large number of join
      operations that would be required by relational database systems. An additional
      advantage of using property profile matching is that searches can be carried out
      allowing a pre-set number of mismatches. Also, as the database is read-only,
      SCAN3D does not need interactive data update mechanisms. Queries typical of a
      molecular engineering environment are demonstrated with specific examples:
      analysis of peptides that induce local structure, analysis of site-dependent
      rotamers and residue--residue contact analysis.

PMID- 8140092
TI  - An algorithm for automatically generating protein topology cartoons.
AB  - An algorithm is described for automatically generating protein topology cartoons.
      This algorithm optimally places circles and triangles depicting alpha-helices and
      beta-strands respectively giving a pictorial topological summary of any protein
      structure. beta-Sheets, sandwiches and barrels are automatically identified and
      represented using special templates. The output from this algorithm may be
      controlled by adjustment of variable weights during the optimization step giving
      a preferred result. The rules for generating protein toplogy cartoons, including
      consideration of the handedness of local structure motifs, are discussed. The
      design of this algorithm is completely general and is easily adapted to include
      further rules that dictate the generation of the cartoons.

PMID- 8140093
TI  - Molecular surface recognition by a computer vision-based technique.
AB  - Correct docking of a ligand onto a receptor surface is a complex problem,
      involving geometry and chemistry. Geometrically acceptable solutions require
      close contact between corresponding patches of surfaces of the receptor and of
      the ligand and no overlap between the van der Waals spheres of the remainder of
      the receptor and ligand atoms. In the quest for favorable chemical interactions,
      the next step involves minimization of the energy between the docked molecules.
      This work addresses the geometrical aspect of the problem. It is assumed that we
      have the atomic coordinates of each of the molecules. In principle, since
      optimally matching surfaces are sought, the entire conformational space needs to
      be considered. As the number of atoms residing on molecular surfaces can be
      several hundred, sampling of all rotations and translations of every patch of a
      surface of one molecule with respect to the other can reach immense proportions.
      The problem we are faced with here is reminiscent of object recognition problems
      in computer vision. Here we borrow and adapt the geometric hashing paradigm
      developed in computer vision to a central problem in molecular biology. Using an
      indexing approach based on a transformation invariant representation, the
      algorithm efficiently scans groups of surface dots (or atoms) and detects
      optimally matched surfaces. Potential solutions displaying receptor--ligand
      atomic overlaps are discarded. Our technique has been applied successfully to
      seven cases involving docking of small molecules, where the structures of the
      receptor--ligand complexes are available in the crystallographic database and to
      three cases where the receptors and ligands have been crystallized separately. In
      two of these three latter tests, the correct transformations have been obtained.

PMID- 8140094
TI  - Structure-activity studies of human tumour necrosis factors.
AB  - The mechanism by which tumour necrosis factors (TNF and lymphotoxin, also called
      TNF alpha and TNF beta respectively) exert their cytotoxic activity on many
      malignant cells, remains largely unknown. Furthermore, the broad array of
      differentiation (gene induction) and mitogenic activities towards many primary
      cells is still a subject of intensive investigation. TNF is an important mediator
      in inflammation, immune responses and infection-related phenomena and these
      activities contribute to the severe toxicity seen when TNF is used as an
      anticancer agent. The first step in the mechanism of action is the specific
      binding of the ligand to its receptors and dissection of the molecular mechanism
      involved in this interaction is the subject of this review. The reasons for the
      interest in this aspect are obvious: first, the development of strong
      antagonistic TNF analogues can be useful in dampening the potentially lethal or
      debilitating effects of an overproduction of the cytokine (as in septic shock or
      rheumatoid arthritis). Secondly, since two distinct TNF receptors exist,
      construction of TNF muteins that distinguish between both types may lead to
      derivatives of this pleiotropic agent with a more restricted biological activity
      pattern. Ideally, one would like to develop a TNF mutant that has retained its
      cytotoxic action on tumour cells without inducing the deleterious systemic
      toxicity. Such an optimized TNF molecule could become a potent anticancer agent.

PMID- 8140095
TI  - Evolutionary divergence and conservation of trypsin.
AB  - The trypsin sequences currently available in the data banks have been collected
      and aligned using first the amino acid sequence homology and, subsequently, the
      superposed crystal structures of trypsins from the cow, the bacterium
      Streptomyces griseus and the fungus Fusarium oxysporum. The phylogenetic tree
      constructed according to this multiple alignment is consistent with a continuous
      evolutionary divergence of trypsin from a common ancestor of both prokaryotes and
      eukaryotes. Comparison of crystal structures reveals a strict conservation of
      secondary structure. Similarly, in the alignment of all the sequences, insertions
      and deletions occur only in regions corresponding to loops between the secondary
      structure elements in the known crystal structures. The conserved residues
      cluster around the active site. Almost all conserved residues can be associated
      with one of the basic functional features of the protein: zymogen activation,
      catalysis and substrate specificity. In contrast, the residues of the hydrophobic
      core of the protein and the calcium ion binding sites are generally not
      conserved. The conserved features of trypsin and the nature of the conservation
      are discussed in detail.

PMID- 8140096
TI  - An alternate-subsite-coupled model for predicting HIV protease cleavage sites in
      proteins.
AB  - A 2-4-6 subsite-coupled model is proposed to predict the cleavability of peptide
      sequences by HIV protease. For an enzyme with eight extended specificity
      subsites, such as HIV protease, the coupling effects of the second subsite with
      the fourth one and the fourth with the sixth subsite are much more important than
      those of the others. Accordingly, in establishing a model for predicting whether
      a given peptide can be cleaved by HIV protease, the 2-4-6 subsite-coupled effect
      must be incorporated. The model leads to an algorithm for predicting protease
      susceptible sites from primary structure. The high rate of correct prediction for
      both HIV-1 and HIV-2 proteases has borne out that this kind of alternation
      coupled mechanism does exist along the extended subsites of HIV protease. The
      principle of the new method can be used for analyzing the specificity of any
      multisubsite enzyme. In particular, the new method can serve as a supplementary
      means for finding effective inhibitors of HIV protease, which is one of the
      targets in designing potential drugs for AIDS therapy.

PMID- 8140097
TI  - The double catalytic triad, Cys25-His159-Asp158 and Cys25-His159-Asn175, in
      papain catalysis: role of Asp158 and Asn175.
AB  - The 1.65 A X-ray structure of papain, which exhibits a Cys25-His159-Asn175 triad,
      does not correspond to the catalytically active ion pair state since Cys25 is
      oxidized to cysteic acid and His159 is predominantly neutral. Thus, stochastic
      boundary molecular dynamics simulations starting from the 1.65 A X-ray structure
      of papain have been performed for Cys25 and His159 in the SH-ImH+, SH-Im, S(-)
      ImH+ and S(-)-Im states and for Asp158 mutated to Asn, Glu and Gly in the ion
      pair state. By comparing the resulting averaged structures and analyzing the
      trajectories of certain interatomic distances, important differences in the
      active-site geometry of papain have been found. In particular, the initial
      Cys25(S-)-His159(ImH+)-Asn175(C = O) triad found in the X-ray structure is
      retained in all the structures except the wild type and Asp158-->Asn ion pair
      states where there is a conformational transition to form the triad, Cys25(S-)
      His159(ImH+)-Asp158(COO-). Both triads, Cys25(S-)-His159(ImH+)-Asp158(COO-) and
      Cys25(S-)-His159(ImH+)-Asn175(C = O) are postulated to participate in catalysis
      and their roles are discussed. Thus, catalysis does not take place from a single
      steric position but a two-state mechanism.

PMID- 8140098
TI  - Herpes thymidine kinase mutants with altered catalytic efficiencies obtained by
      random sequence selection.
AB  - We have obtained 190 active Herpes simplex virus type 1 thymidine kinase mutants
      by substituting a 33 nucleotide sequence with 20% degeneracy for a portion of the
      nucleotide sequence that encodes the putative thymidine binding site [K.M. Munir,
      D.C. French, D.K. Dube and L.A. Loeb (1992) J. Biol. Chem., 167, 6584-6589]. In
      order to classify these mutants with respect to thymidine kinase activity we
      determined the ability of Escherichia coli harboring these mutants to form
      colonies in the presence of varying concentrations of thymidine. Escherichia coli
      harboring one of the mutant enzymes was able to form colonies at a concentration
      of thymidine lower than did the wild type. It was able to phosphorylate thymidine
      more rapidly than the wild type both in vivo and in vitro. The increased
      thymidine kinase activity was manifested by (i) a 42% enhanced uptake of [methyl
      3H]thymidine into E. coli, (ii) a 2.4 times higher rate of [methyl-3H]thymidine
      incorporation into acid-insoluble material and (iii) a 5-fold increase in the
      kcat of the purified enzyme compared to the wild type. Herpes thymidine kinase
      purified from other mutants that formed colonies at higher thymidine
      concentrations than that of the wild type exhibited a decrease in kcat. The kcat
      of one of these mutant thymidine kinases was 10(-4) of that of the wild type
      enzyme. This study demonstrates that a spectrum of mutant enzymes with different
      catalytic properties can be obtained by selection from a plasmid with random
      sequence substitutions and this can be done in the absence of rational protein
      design.

PMID- 8140099
TI  - A pore-forming protein with a protease-activated trigger.
AB  - alpha-Hemolysin (alpha HL) is a 293 amino acid pore-forming toxin, which is
      secreted as a water-soluble monomer by Staphylococcus aureus. By forming a
      hexameric pore, alpha HL damages the plasma membranes of target cells. Previous
      studies established that alpha HL proteins with nicks near the midpoint of a
      central glycine-rich loop are held together by a domain-domain interaction and
      are hemolytically active. In contrast, alpha HL proteins comprising two alpha HL
      truncation mutants that overlap in the central loop have no or greatly reduced
      pore-forming activity, even though the two chains again form a tight complex.
      Based on these findings, overlap mutants have now been designed that are
      activated when redundant amino acids in the loop are removed by proteases.
      Further, the identity of the activating enzyme can be specified by additional
      mutagenesis of the protease recognition site in the overlap sequence. Mutants of
      alpha HL that are activated by tumor-associated proteases might be useful
      components of immunotoxins.

PMID- 8140101
TI  - Part time workers need equal consideration.

PMID- 8140100
TI  - Chemical modification and site-directed mutagenesis of Tyr36 of 3-isopropylmalate
      dehydrogenase from Thermus thermophilus HB8.
AB  - 3-Isopropylmalate dehydrogenase from an extreme thermophile, Thermus thermophilus
      HB8, was chemically modified with tetranitromethane which nitrated 1.5-2.0 Tyr
      residues per subunit. The nitration was biphasic and parallel to the loss of
      activity. The modified residue in the first phase was identified to be Tyr36,
      which is distantly located from the active site of the enzyme. The function of
      Tyr36 was investigated by site-specific replacement with Phe. The Michaelis
      constant for the substrate or co-enzyme was not altered by the replacement,
      whereas the catalytic constant decreased down to approximately 5%. X-ray analysis
      of the mutant enzyme revealed that Arg94 moved the largest distance among the
      active site residues, that is, the NH1 and NH2 of the guanidino group moved 1.11
      and 1.32 A respectively. The results suggest that Arg94 is responsible for the
      enzyme catalysis.

PMID- 8140102
TI  - A vital component of care: the nurse's role in recognising altered body image.
AB  - Using the example of people with spinal injuries, this article examines the
      impact of illness or injury on people's body image. Successful assessment and
      evaluation by nurses of altered body image--from physical, psychological and
      social angles--are vital components of patient care and support.

PMID- 8140103
TI  - A last bastion of ritualised practice? A review of nurses' knowledge of oral
      healthcare.
AB  - Evidence suggests that oral healthcare is often carried out in a ritualized
      manner, without reference to patients' individual needs. A survey undertaken to
      assess a ward's oral healthcare practice identified the need for implementation
      of an oral health assessment tool.

PMID- 8140104
TI  - Meningitis: causes, treatment and care.
AB  - 1. About 10-25 per cent of the general population may be carriers of bacterial
      meningitis. 2. Rifampicin may be given to close contacts of the patient and on
      discharge. 3. Counselling the patient and family on complications after
      meningitis is essential. 4. Education on meningitis for nurses could be improved
      to enable them to act effectively in the community.

PMID- 8140105
TI  - Putting practice into theory. Developing the role of the link teacher in higher
      education.

PMID- 8140106
TI  - Know your patient. The importance of assessment in care delivery.
AB  - Assessment is the first part of the nursing process, and thus forms the basis of
      the care plan. The essential requirement of accurate assessment is to view
      patients holistically and thus identify their real needs.

PMID- 8140107
TI  - A closer look at disposable gloves. An assessment of the value of vinyl, latex
      and plastic gloves.
AB  - Research has shown that people with broken skin can be at serious risk of cross
      infection. A study was undertaken to assess the relative benefits of wearing
      vinyl, latex and plastic gloves during invasive procedures.

PMID- 8140108
TI  - Complementary treatments for eczema in children.
AB  - 1. Complementary therapies are just that and not an alternative to routine
      therapies. 2. The growing use of complementary therapies for eczema reflects a
      renewed interest in self-medication and a declining belief in orthodox medicine.
      3. Prior to using essential oils, nurses should check for sensitivity to certain
      oils. 4. Herbalism offers a number of approaches to the treatment of eczema.

PMID- 8140109
TI  - Finding the means to carry on. Suicidal feelings in cancer patients.
AB  - People suffering from advanced cancer may question the point of carrying on. It
      is essential that nurses are sensitive to patients' suicidal feelings at such
      times, and that a multidisciplinary assessment is made of the patient's key
      concerns. By bringing such problems into the open, these concerns may begin to be
      addressed.

PMID- 8140110
TI  - A major problem needing recognition. Assessment and management of elder abuse and
      neglect.
AB  - While the abuse of children and adults receives widespread coverage, that of
      older people has only recently been acknowledged. It is vital that nurses improve
      their understanding of this problem, so they can participate effectively in
      multidisciplinary assessment and care.

PMID- 8140111
TI  - The dressing makes the difference. Trial of two modern dressings on venous
      ulcers.
AB  - Despite the plethora of modern dressings available for leg ulcers, and the huge
      financial and social cost of inappropriately treated ulcers, many are still left
      virtually untreated. This comparison of two modern dressings illustrates the
      benefits of using appropriate dressings.

PMID- 8140112
TI  - A fellowship in New York.

PMID- 8140113
TI  - Liquid chromatography-mass spectrometry of lipids.

PMID- 8140114
TI  - Structure, function and biogenesis of storage lipid bodies and oleosins in
      plants.

PMID- 8140116
TI  - Monthly prostaglandin bibliography prepared by Sheffield University Biomedical
      Information Service.

PMID- 8140115
TI  - Lipids of bryophytes.

PMID- 8140117
TI  - Structural and functional aspects of cytosolic fatty acid-binding proteins.

PMID- 8140118
TI  - Distribution of unsaturated fatty acids in phospholipids of arteries from
      nonpregnant, pregnant and fetal sheep.
AB  - Normal ovine pregnancy is associated with elevated levels of circulating
      vasodilator prostaglandins (PGs) and increases in PG production by uterine and
      systemic arteries. We hypothesized that the availability of fatty acid substrate
      may regulate PG production in vasculature from nonpregnant, pregnant and fetal
      sheep. In pregnant sheep, levels of arachidonic acid (20:4 omega 6), the
      immediate PG precursor, were significantly lower in phospholipids from uterine
      versus systemic (renal) arteries. Although linoleic acid (18:2 omega 6), the
      primary arachidonic acid precursor, was elevated (p < 0.001) in uterine arteries
      during pregnancy, levels in systemic arteries were decreased. Levels of omega 3
      polyunsaturated fatty acids (PUFAs) also were increased (p < 0.001) in both
      uterine and systemic arteries during pregnancy. In fetal-placental arteries, the
      levels of arachidonic and linoleic acid were 50 and 90% less, respectively, than
      that in maternal arteries. We conclude that during ovine pregnancy vascular
      prostanoid production may be regulated, in part, by the availability of fatty
      acid precursors.

PMID- 8140119
TI  - Epidermal growth factor and transforming growth factor-alpha enhance the
      interleukin-1- and tumor necrosis factor-stimulated prostaglandin E2 production
      and the interleukin-1 specific binding on amnion cells.
AB  - Interleukin-1 (IL-1), tumor necrosis factor (TNF), epidermal growth factor (EGF),
      and transforming growth factor-alpha (TGF-alpha) stimulate prostaglandin E2
      (PGE2) production by amnion cells whereas TGF-beta inhibits the PGE2 production.
      During labor occurring in the setting of infection, several of these cytokines
      may be simultaneously present in amniotic fluid. The aim of the present study was
      to examine whether these cytokines modify each others' effects on amnion cell
      PGE2 production. Amnion cells in monolayer culture were treated with IL-1, TNF,
      EGF, TGF-alpha, TGF-beta 1, their combination, or vehicle. The PGE2 production
      and the specific binding of radiolabeled IL-1 beta on the cells were measured. IL
      1 or TNF in combination with EGF or TGF-alpha stimulated synergistically the
      production of PGE2 by amnion cells. TGF-beta 1 did not modify the PGE2
      stimulatory effect of EGF/TGF-alpha. Untreated amnion cells expressed 1030 +/-
      100 IL-1 beta receptors per cell with a binding affinity of 1.40 +/- 0.26 nM.
      Treatment with TGF-alpha increased the number of receptors to 3940 +/- 260 per
      cell with no change in binding affinity. The potentiation of the PGE2-stimulatory
      effect of IL-1 by TGF-alpha may be related to its ability to induce IL-1
      receptors on amnion cells. The synergistic effects of cytokines on amnion cell
      PGE2 production may promote labor.

PMID- 8140120
TI  - Use of a continuous assay of oxygen consumption to evaluate the pharmacology of 5
      lipoxygenase inhibitors.
AB  - A variety of assay systems have been utilized to evaluate the inhibition of the
      key enzyme in leukotriene (LT) biosynthesis, 5-lipoxygenase (5-LO). We have
      developed an assay utilizing a cytosolic preparation of 5-LO from rat basophilic
      leukemia (RBL-1) cells. Enzyme activity was monitored by continuous measurement
      of oxygen consumption. High performance liquid chromatography (HPLC) analysis of
      products showed exclusive generation of 5-LO products. The assay proved useful
      for the evaluation of a variety of chemical classes of lipoxygenase inhibitors
      and clearly differentiated those compounds which extended the lag phase (e.g. A
      64077) as opposed to the propagation phase of the enzyme activity (e.g. SK & F
      105561). The data generated were in reasonable agreement with results from the
      assay of isolated human monocyte 5-LO and, with the exception of compounds which
      appear to have a significant effect on 5-LO translocation (e.g. MK-886 and Wy-49
      232), inhibition of LT production by intact monocytes. This assay system proved
      to be a convenient and informative method to analyze inhibition of 5-LO activity.

PMID- 8140121
TI  - SC-46275: a potent and highly selective agonist at the EP3 receptor.
AB  - The agonist properties of SC-46275 have been investigated in EP receptor subtype
      specific smooth muscle assays. In the isolated guinea pig vas deferens (GPVD),
      prostaglandin E2 (PGE2), via the EP3 receptor, potently inhibited electrically
      induced contractions with an EC50 of 5.4 +/- 1.1 nM. Sulprostone and misoprostol
      were both potent relaxers of the GPVD yielding EC50s of 1.6 +/- 0.4 nM and 4.3 +/
      0.9 nM, respectively, while butaprost (10,000 nM) was inactive. SC-46275 was by
      far the most potent agonist in the GPVD exhibiting an EC50 of 0.04 +/- 0.02 nM.
      PGE2, via the EP1 receptor, stimulates contractions in the longitudinal muscle
      layer of the guinea pig ileum (GPIL) with an EC50 of 74.4 +/- 10.6 nM. SC-46275
      was extremely weak in this preparation, generating only 33% of the maximal PGE2
      effect at 30,000 nM. The circular muscle layer of guinea pig ileum (GPIC) is
      responsive to inhibition of electrically stimulated contractions by PGE2 (EC50 =
      179.6 +/- 20.8 nM) via the EP2 receptor. SC-46275 (up to 10,000 nM) was
      completely inactive in this preparation. We conclude from these findings that SC
      46275 is a very potent and highly selective EP3 receptor agonist. SC-46275 should
      prove to be an extremely valuable tool in probing the physiological significance
      of EP3 receptors. The high potency of SC-46275 at the EP3 receptor may account
      for its antisecretory and cytoprotective actions, while its lack of activity at
      the EP1 or EP2 sites may explain its very weak diarrheagenic potential.

PMID- 8140122
TI  - Macrophage prostaglandin E2 and oxidative responses to endotoxin during
      immunosuppression associated with anaesthesia and transfusion.
AB  - The widespread use of blood transfusion in major surgical procedures has led to
      concern about the immunosuppressive effect of transfusion on patients with
      underlying malignancy. Transfusion may also suppress the host response to
      infection. The cellular mechanisms of transfusion-associated immunosuppression
      may involve macrophage prostaglandin E2 (PGE2) in modulating the host response to
      cancer and infection. We previously observed that the transfusion of blood
      increased PGE2 production by unstimulated macrophages. To investigate this PGE2
      associated immunosuppression, we studied the effect of transfusion of rats using
      a physiological stimulus of macrophage PGE2 production, bacterial endotoxin. In
      the same macrophages, we analysed intracellular oxidative activity. Both
      allogeneic and syngeneic blood transfusion were associated with increased PGE2
      release by macrophages. This stimulation of PGE2 increased with duration of
      storage of blood. A similar effect of serum indicated that a humoral factor was
      involved. Endotoxin (50 ng/ml-500 micrograms/ml) stimulated PGE2 production in
      all transfused subjects. The lowest endotoxin concentration gave proportionately
      the greatest stimulation. Oxidative activity was down-regulated in macrophages of
      transfused rats, supporting an immunosuppressive role of PGE2 within the
      macrophage. An effect of surgery on the oxidative response was also detected.

PMID- 8140123
TI  - Comparison of the potency of various serotypes of E. coli lipopolysaccharides in
      stimulating PGI2 production and suppressing ACE activity in cultured human
      umbilical vein endothelial cells.
AB  - We investigated the potency of various serotypes of lipopolysaccharides (LPS) by
      examining LPS-induced stimulation of PGI2 production and suppression of ACE
      activity in cultured human umbilical vein endothelial cells (HUVEC). HUVEC which
      had been incubated with E. coli 055:B5 and 0111:B4 for 24 h produced more
      prostacyclin (PGI2) in response to thrombin than HUVEC incubated with E. coli
      026:B6. Also, angiotensin converting enzyme activity (ACE) in cell lysates of
      HUVEC incubated for 24 h with 055:B5 or 0111:B4 was suppressed significantly
      compared to control HUVEC or HUVEC incubated with 026:B6. From these experimental
      results, E. coli 055:B5 and 0111:B4 appear to be more potent than 026:B6. It is
      concluded that this difference in potency among various serotypes of LPS should
      be taken into account when experiments are designed to examine the effect of LPS
      on endothelial cell function.

PMID- 8140124
TI  - Actions of interleukin-2 on amnion prostaglandin biosynthesis.
AB  - Preterm labor is associated with increased intrauterine prostaglandin (PG)
      production. Intrauterine infections are frequently associated with preterm labor
      and increased cytokine production. The cytokine interleukin-2 (IL-2) is a potent
      T-cell growth factor necessary for effective cell-mediated immunity. In this
      study we evaluated the effects of IL-2 on PGE2 biosynthesis by human amnion
      cells. IL-2 alone modestly but significantly inhibited amnion PGE2 production.
      Moreover, IL-2 also attenuated, in a concentration-related fashion, the
      stimulatory actions of IL-1 beta on PGE2 production by amnion cells. These data
      suggest that IL-2 could potentially represent a negative regulatory element in
      the mechanisms of preterm labor in association with intrauterine infection.

PMID- 8140125
TI  - Interleukin-1 beta stimulates prostaglandin E2 and F2 alpha synthesis in human
      ovarian granulosa cells in culture.
AB  - To evaluate the roles of interleukin-1 (IL-1) in regulation of ovarian
      prostaglandin (PG) synthesis, we examined the effects of IL-1 beta on PGE2, PGE2
      alpha, 6-keto-PGF 1 alpha and thromboxane (TX) B2 synthesis in cultures of human
      ovarian granulosa cells. Granulosa cells were obtained from hyperstimulated
      follicles in patients undergoing oocyte retrieval for in vitro fertilization
      embryo transfer (IVF-ET). IL-1 beta increased immunoreactive concentrations of
      PGE2 and PGF2 alpha in culture medium in time- and dose-dependent manners.
      Concentration of PGE2 was significantly higher after 24 h incubation with 5 or
      more units/ml of IL-1 beta, when compared to the control value obtained without
      IL-1 beta (P < 0.05). Concentration of PGF2 alpha was significantly higher after
      8 h incubation with more than 2 units/ml of IL-1 beta (P < 0.05). The increase in
      PGE2 was observed even in the presence of human chorionic gonadotropin (hCG), and
      blocked by indomethacin, an inhibitor of cyclooxygenase. During a 10 day
      incubation period, stimulatory effects of IL-1 beta on PG synthesis were observed
      only on the first 2 days incubations. Concentrations of 6-keto-PGF 1 alpha and
      TXB2 were below our measurement limits. This study demonstrated that IL-1 beta
      stimulates PG synthesis in human ovarian granulosa cells in vitro. IL-1 seems to
      play an important role in regulating ovarian functions.

PMID- 8140126
TI  - Effects of a fish oil rich diet on hyperoxic lung damage in mice.
AB  - Mice were fed a chow diet plus 10% cellulose, 10% fish oil or 10% sunflower oil
      for 3 weeks, then exposed to 100% oxygen for 75 h. Large changes in lung fatty
      acid composition occurred, but this did not affect hyperoxic lung damage nor
      levels of thiobarbituric acid reactive substances or myeloperoxidase in lungs of
      mice following exposure to hyperoxia. Thus there is no evidence that the
      ingestion of large quantities of fish oil increased the susceptibility to the
      oxidative stress induced by hyperoxia.

PMID- 8140127
TI  - Synthesis, toxicity and immunomodulating activity of Co(II), Ni(II), Cu(II) and
      Zn(II) complexes of L(-)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]thiazole
      (levamisole).
AB  - Co(II), Ni(II), Cu(II) and Zn(II) complexes of levamisole (LMS) were prepared and
      characterized by elemental analyses, IR spectroscopy, 1H and 13C NMR and mass
      spectrometry. The following general formula was derived: M(LMS)2Cl2, where M =
      Co, Ni, Cu, Zn. It was established that LMS behaved as a monodentate ligand and
      the coordination was accomplished through the N-7 atom. The toxicity and the
      immunomodulating activity of the complexes on mice and rats in comparison with
      uncomplexed LMS was assayed. The metals in the complexes exerted different
      changes in the toxicity of LMS. The complex containing Zn(II) was less toxic and
      manifested higher immunomodulating activity than LMS.

PMID- 8140128
TI  - [HPLC determination of diprafenone and its active metabolite 5-hydroxydiprafenone
      in human plasma].
AB  - A simple, specific and sensitive HPLC method is described, which allows the
      quantitation of diprafenone and its active metabolite 5-hydroxydiprafenone in
      human plasma. Propafenone is used as internal standard. After extraction by
      diethyl ether from plasma, the analytes are reextracted with 5% phosphoric acid
      from the organic phase. Chromatographic separation on a RP-18 column and UV
      detection (220 nm) allows the sensitive determination of diparafenone and 5
      hydroxydiprafenone in plasma with a lower limit of quantitation of 5.0 ng/ml for
      both substances. The method was successfully applied to human plasma samples from
      24 subjects after oral or i.v. administration of 300 mg or 50 mg diprafenon
      hydrochloride, respectively.

PMID- 8140129
TI  - [Pharmacokinetics and biotransformation of 3-cyan-2-morpholino-5-(pyrid-4
      yl)pyridine (AWD 122-14) in the rat].
AB  - A sensitive isocratic HPLC method for the analysis of AWD 122-14 (1) in plasma
      and urine was developed. The extraction was processed on-line on a short column.
      The pharmacokinetics of 1 was studied in rats. The plasma concentration-time
      course was described by an 1-compartment-model. The pharmacokinetic parameters
      were estimated. The absorption and elimination of 1 are relatively fast. A single
      oral dose (D = 1 x 10(-5) mol/kg) was rapidly absorbed (absorption rate constant:
      kI = 6.85 h-1). The elimination rate constant is kE = 1.59 h-1. The absolute
      bioavailability of a single oral dose equals 11%. In rats 1 is mainly
      metabolized. Less than 5% of the dose is excreted in the urine as unchanged drug.
      The chemical structures of 10 of the 12 isolated metabolites were determined
      using high-resolution mass spectrometry.

PMID- 8140130
TI  - Pharmacokinetics and distribution of selenium in blood and organs of rats.
AB  - The dynamics of selenium concentration changes in blood, organs and tissues of
      rats after a single intragastric administration of selenium yeast and sodium
      selenite was determined. The course of selenium concentration changes in blood
      was described, the pharmacokinetic parameters were estimated according to the
      trivalent equation of dicompartment model and the selenium content in liver,
      kidneys, small intestine, spleen, heart, brain, stomach, testicles and prostate
      was determined 48 h after the administration of selenium preparations.

PMID- 8140131
TI  - Inhibition of lipoperoxidation of linoleic acid by five antioxidants of different
      lipophilicity.
AB  - The efficacy of oxidation inhibition of five natural and synthetic antioxidants
      (BHT, BHA, nordihydroguaiaretic acid (NDGA), quercetin and rutin) was studied in
      O/W emulsions. Linoleic acid was used as a reference molecule; the reaction was
      initiated by an azo-compound. The kAH characterizing the reaction of the
      antioxidant with the peroxyl radical decreases in the following order: kAH(BHA) >
      kAH(BHT) > kAH(NDGA) > kAH(quercetin) > kAH(rutin).

PMID- 8140132
TI  - 2-(6-Acyl-2-benzoxazolinone-3-yl)acetamide and acetonitrile derivatives with
      analgesic activities.

PMID- 8140133
TI  - Synthesis of 2,3-dihydro-3-amino-6-phenyl-2-thioxothieno [2,3-d] pyrimidin-4 (1H)
      one and of potential antiinflammatory agents 2-aryl-7-phenyl-3H, 9H-pyrimido [2,1
      b]thieno-[2',3':4,5]]1,3,4] thiadiazin-9-ones.

PMID- 8140134
TI  - [Synthesis, physico-chemical and antimicrobial activities of 1-alkyl-2
      (pyridyl)pyridinium bromides].

PMID- 8140135
TI  - Some 1,3,5-triphenyl-2-pyrazolines with antidepressant activities.

PMID- 8140136
TI  - Free radical scavenger prodrugs--potentially potent brain penetrating agents.

PMID- 8140137
TI  - Application of ternary complexes in pharmaceutical analysis. Part 6:
      Spectrophotometric determination of micromolar concentrations of iron (II) and
      iron (III) in anti-anemic formulations using a newly prepared Schiff's base.

PMID- 8140138
TI  - Topical delivery systems for azelaic acid: effect of the suspended drug in
      microemulsion.

PMID- 8140139
TI  - Comparison between the iontophoretic and passive transdermal delivery of timolol
      maleate across human cadaver skin.

PMID- 8140140
TI  - Effect of fasting and stress on transdermal delivery of propranolol in rats.

PMID- 8140141
TI  - [7 beta-hydroxycholesterol, a ubiquitous signal substance in thymus tissue?].

PMID- 8140142
TI  - An impairment and disability assessment and treatment protocol for community
      living elderly persons.
AB  - BACKGROUND AND PURPOSE: Falls and immobility are common among community-living
      elderly persons and result from the accumulated effect of multiple impairments
      and disabilities as well as environmental hazards. We developed and tested a
      simple assessment and intervention protocol for use in prevention and treatment
      programs among community-living elderly persons. This article presents the
      components of the assessment; the criteria for intervening on diagnosed
      impairments contributing to falls and immobility; and the recommended treatments,
      environmental adaptations, training, and exercise programs targeting the
      diagnosed problems. SUBJECTS: A convenience sample of 11 residents of a senior
      housing complex who were cognitively intact and ambulatory were chosen for
      reliability testing of the assessment protocol. A random sample of 20 of the 153
      elderly subjects involved in a multiple risk factor trial for fall prevention
      then were chosen to test the reliability of the intervention recommendations.
      METHODS: The assessment and intervention protocol was developed by a consensus
      approach among a group consisting of a geriatric physician, two nurses, and three
      physical therapists. The interrater reliability of both the assessment and the
      intervention components of the protocol was determined by comparing the results
      of two of the study physical therapists. RESULTS: There was excellent agreement
      in assessment and intervention results by the two physical therapists. The
      assessment required approximately 45 minutes to complete, suggesting it is
      feasible for use in clinical practice. CONCLUSION AND DISCUSSION: A simple,
      standardized assessment and intervention protocol, such as the one described,
      could aid physical therapists in evaluating and treating community-living elderly
      persons by improving communication among care providers, providing better
      documentation for reimbursers, and ensuring a direct linkage between assessment
      and intervention, thus simplifying the development of a treatment plan for
      elderly persons with complicated or multiple impairments. The ultimate test of
      this assessment and intervention protocol will be ascertainment of the goal of
      the protocol, namely a reduction in falls and improvement in mobility among
      multiply and chronically ill elderly persons.

PMID- 8140143
TI  - Differences in the gait characteristics of patients with diabetes and peripheral
      neuropathy compared with age-matched controls.
AB  - BACKGROUND AND PURPOSE: Patients with diabetes and peripheral neuropathy have a
      high incidence of injuries while walking. Biomechanical analysis of their walking
      may lead to treatments to reduce these injuries. The purpose of this study was to
      compare (1) the gait characteristics, (2) the plantar-flexor peak torques, and
      (3) the ankle range of motion of subjects with diabetes mellitus (DM) and
      peripheral neuropathy with those of age-matched controls. SUBJECTS: Twenty
      subjects, 10 with DM and a history of peripheral neuropathy (DM group) (mean age
      = 58 years, SD = 15, range = 35-75) and 10 subjects without diabetes (NODM group)
      (mean age = 57 years, SD = 11, range = 37-68), were evaluated. METHODS: The
      following data were collected on all subjects: ankle joint mobility, plantar
      flexor peak torque (ankle strength), kinematics of the trunk and lower extremity
      during normal walking, and ground reaction forces. Moments and power at the
      ankle, knee, and hip during walking were calculated using a two-dimensional link
      segment model. RESULTS: The DM group subjects showed less ankle mobility, ankle
      moment, ankle power, velocity, and stride length during walking than the NODM
      group subjects. A significant decrease in ankle strength and mobility appeared to
      be the primary factor contributing to the altered walking patterns of the DM
      group. CONCLUSION AND DISCUSSION: The DM group subjects appeared to pull their
      legs forward using hip flexor muscles (hip strategy) rather than pushing the legs
      forward using plantar-flexor muscles (ankle strategy), as seen in the NODM group
      subjects. Implications for treatment are presented to attempt to reduce the
      number of injuries during walking in patients with DM and peripheral neuropathy.

PMID- 8140144
TI  - A patient with de Quervain's tenosynovitis: a case report using an Australian
      approach to manual therapy.
AB  - This case report describes a 41-year-old female patient who had chronic de
      Quervain's tenosynovitis, which had progressed to include involvement of the
      cervical spine, shoulder girdle, and upper extremity. The patient complained of
      aching over the left scapula, a band of pain around the upper arm, and sharp
      shooting pain in the forearm, with numbness and tingling in the fingers. On
      examination, she had abnormal palpatory findings in the cervical spine, the
      shoulder quadrant maneuver was limited, and the upper-limb tension tests (neural
      structures) were positive. The case report demonstrates the use of an Australian
      approach to manual therapy as described by Maitland. This approach includes (1)
      development, refinement, and rejection of working hypotheses as to the possible
      cause(s) of a patient's symptoms; (2) development of a long-range treatment plan;
      and (3) use of data from treatment responses to guide further treatment
      selection.

PMID- 8140145
TI  - Effects of aerobic exercise on pain perception, affect, and level of disability
      in individuals with fibromyalgia.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the effect of
      aerobic walking on the pain, disability, and psychological symptoms of
      individuals with fibromyalgia. SUBJECTS: Nineteen subjects with fibromyalgia (2
      men, 17 women), aged 30 to 69 years (mean = 49.35, SD = 11.83), participated.
      METHODS: Ten subjects walked 20 minutes, three times per week, for 8 weeks at 60%
      to 70% of the predicted maximum heart rate for their age. Nine subjects served as
      sedentary controls. Each subject completed pretests and posttests of the McGill
      Pain Questionnaire (MPQ), the Sickness Impact Profile (SIP), and the Brief
      Symptom Inventory (BSI). Due to initial differences on all measures, final scores
      were adjusted and analyzed by an analysis of covariance. RESULTS: The
      experimental group had lower scores on the MPQ on two of the three BSI indexes,
      and on the Psychosocial Dimension scale of the SIP, but higher ratings on the
      Physical Dimension scale of the SIP than did the control group on final testing.
      Only the differences on one index of the BSI and the Physical Dimension scale of
      the SIP were significant. CONCLUSION AND DISCUSSION: The results of the study are
      inconclusive. There were trends suggestive of a beneficial response to aerobic
      walking (lower psychological and pain ratings) but limited significant findings
      and higher physical disability ratings, for these individuals with fibromyalgia.

PMID- 8140146
TI  - Comparison of characteristics and attitudes of entry-level bachelor's and
      master's degree students in physical therapy.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to examine the
      relationships between type of entry-level education and selected student
      variables. SUBJECTS: Students in their final year of education in entry-level
      bachelor's and master's degree programs in the United States (N = 766)
      participated in the study. METHODS: Questionnaires were mailed to these students,
      who represented 22 entry-level physical therapy programs selected at random from
      the December 1991 issue of Physical Therapy. Two-tailed t tests for independent
      means and chi-square analyses were performed to determine statistical
      significance for interval data and categorical data, respectively. RESULTS: Five
      hundred twelve surveys were returned, for a response rate of 66.8%. Master's
      degree respondents anticipated greater involvement in research and teaching and
      felt better prepared to practice across a broad spectrum of clinical practice and
      to perform activities related to research, teaching, management, and direct
      access practice. Baccalaureate programs, however, appeared to attract a greater
      percentage of minority individuals (14.9% versus 5.8%, respectively). CONCLUSION
      AND DISCUSSION: These results suggest that differences exist between entry-level
      bachelor's and master's degree students in physical therapy. Findings of this
      study may have implications for curriculum planning, recruitment and scholarship
      efforts, and policy formation in physical therapy education.

PMID- 8140147
TI  - Reliability of measurements of static weight distribution of manual wheelchairs.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the reliability
      of measurements of weight distribution among the wheels of wheelchairs using a
      commercial balance testing system. Reliable data may be useful in the wheelchair
      evaluation and adjustment process. SUBJECTS: Three male full-time manual
      wheelchair users aged 30, 26, and 27 years with cervical spinal cord injuries
      7.5, 6.5, and 10 years in duration participated. METHODS: Calibration weights,
      unoccupied wheelchairs, and occupied wheelchairs were repeatedly placed on the
      force transducers of the balance testing system to obtain measurements of weight
      distribution. RESULTS: The intraclass correlation coefficients of the
      measurements were .99 for calibration weights, .96 for unoccupied wheelchairs and
      .98 for wheelchairs occupied by the subjects. CONCLUSION AND DISCUSSION: The
      described use of this instrumentation appears to generate reliable measurements
      of static weight distribution. With further testing, this system may provide
      useful information related to manual wheelchair prescription and adjustment.

PMID- 8140148
TI  - Content of physician referrals to physical therapists at clinical education sites
      in Indiana.
AB  - BACKGROUND AND PURPOSE: The content of physician referrals to physical therapists
      was studied as an indicator of the level of decision making required of physical
      therapists. SUBJECTS AND METHODS: Seventeen managers of clinical education sites
      in Indiana provided diagnosis and treatment information on a total of 2,267
      patient referrals. RESULTS: Differential diagnoses were specified in 39.6% of the
      referrals, and specific treatment orders were present in 32.6% of the referrals.
      Outpatient referrals contained significantly fewer diagnoses (29.1%) and specific
      orders (28.2%) than did inpatient referrals (56.0% and 39.5%, respectively).
      CONCLUSION AND DISCUSSION: These results indicate that physical therapists
      working in clinical education sites in Indiana must frequently exercise
      independent decision-making skills in determining the nature of the patient
      complaint and the appropriate treatment for the complaint. Academic programs that
      choose to expose students to a full range of decision-making situations should
      ensure a balance between inpatient and outpatient experiences.

PMID- 8140149
TI  - Effects of high-frequency transcutaneous electrical nerve stimulation on limb
      blood flow in healthy humans.
AB  - BACKGROUND AND PURPOSE: Although transcutaneous electrical nerve stimulation
      (TENS) has been used clinically for more than 20 years, the hemodynamic effects
      of this intervention remain controversial. Our goal was to determine the effects
      of high-frequency TENS on calf blood flow in healthy subjects. SUBJECTS: Four men
      and seven women ranging in age from 20 to 44 years (mean = 30, SD = 9) served as
      subjects. METHODS: We measured calf blood flow during 20-minute TENS applications
      over the common peroneal and tibial nerves at intensities above and below the
      motor threshold. RESULTS: Calf blood flow was not changed by sensory-level TENS
      (3.2 +/- 1.0 versus 2.9 +/- 1.0 mL/100 mL/min) or by motor-level TENS (3.1 +/-
      1.2 versus 2.8 +/- 1.0 mL/100 mL/min). CONCLUSION AND DISCUSSION: Neither sensory
      level nor low-intensity motor-level TENS applied over peripheral nerves at
      clinically relevant pulse durations and frequencies altered limb blood flow in
      asymptomatic individuals. The applicability of these findings in conditions of
      abnormally elevated or diminished vascular resistance has not been determined.

PMID- 8140150
TI  - The effect of kindling of different nuclei in the left and right amygdala on
      anxiety in the rat.
AB  - The effects on rodent anxiety of kindling in the medial or basolateral amygdaloid
      nuclei in each hemisphere were examined. Anxiety was measured using the hole
      board and elevated plus maze tests. The animals were kindled in medial or
      basolateral amygdalas, of either the left or right hemisphere. Controls had
      electrodes implanted in comparable areas, but were not kindled. Analysis of
      electrode location showed that some animals were kindled in amygdaloid nuclei
      other than medial or basolateral amygdala. These animals were labelled outliers.
      Kindling of the medial/basolateral amygdala in the left hemisphere decreased
      anxiety for at least 1 week after the last kindled seizure. Right hemisphere
      medial/basolateral kindling tended to increase anxiety. Outlier-kindled rats were
      less anxious than their controls regardless of hemisphere 1 week after their last
      kindled seizure. Clear anxiogenic effects were not likely seen in the right
      hemisphere in this study because of the electrode locations. The degree of
      anxiety following kindling was correlated with electrode location in the anterior
      posterior plane. More anterior foci in the amygdala were associated with more
      anxiety. More posterior amygdala foci were associated with less anxiety. These
      findings point to the importance of kindled focus in the amygdala for behavioral
      effect. Future research should carefully control the location of kindled foci
      when investigating effects of amygdala kindling on anxiety and other behaviors.

PMID- 8140151
TI  - Postoperative changes of rat EEG variance.
AB  - Concerning an EEG parameter variance, the long-term postoperative changes were
      observed in rats chronically implanted with bipolar depth electrodes for EEG
      recordings. The cortico-hippocampal EEG signals were continuously digitized and
      their variances were computed for each 1 min in real time. Daily mean of the EEG
      variance gradually increased over 2 weeks after surgery for the implantation of
      chronic electrodes and, then, reached a plateau. To observe the absolute quantity
      of the depth EEG in the rat, at least 2 weeks are required before data
      collections.

PMID- 8140152
TI  - Phase angle changes of photically entrained circadian rhythms following a single
      nonphotic stimulus.
AB  - Syrian hamsters entrained to a light-dark (LD) cycle of 14:10 h were given the
      opportunity to run in novel wheels for 3 h in the middle of the light phase. This
      manipulation transiently altered the phase angle of entrainment to the LD cycle:
      activity onset was significantly advanced (by about 0.5 h) on the day after the
      pulse and gradually drifted back toward its prepulse time. When animals were held
      in LD 11.5:12.5 h, a photoperiod in which onset time occurs later relative to the
      time of lights-off, they again advanced about 0.5 h in response to the pulse of
      wheel running, but many animals retained an advanced phase angle for at least 7
      days, and some for more than 21 days. Individual changes in phase angle were
      highly correlated with the prepulse phase angle: the more negative the phase
      angle, the greater the advance subsequent to the novel wheel pulse. These results
      show that a single, short-duration, nonphotic manipulation can produce long
      lasting alterations in the phase angle of entrainment to a LD cycle.

PMID- 8140153
TI  - Stress-induced hyperthermia in mice: a methodological study.
AB  - When the rectal temperature of group-housed mice is measured sequentially, the
      temperature of the last measured mouse is higher than that of the first mouse.
      This phenomenon is called stress-induced hyperthermia (SIH). We varied several
      experimental parameters to elucidate the mechanism behind this SIH. SIH was
      stable and found by all technicians performing the experiments. The large
      intertechnician difference in the mean rectal temperature could be eliminated by
      training in an identical fixation and handling technique. SIH was both
      independent of the number of handling days preceding the experiment and of the
      number of disturbances (0, 1, 2, or 5) implied on the mice per minute. The
      percentage of hyperthermic mice in 10-mice cages increased when the time interval
      between the individual measurements increased from 1 to 2, 5 or 10 min. In all
      groups the maximum increase was reached after an interval of approximately 10
      min. SIH of mouse 10 returned time dependently in approximately 60 min to basal
      temperature. When SIH was tested on 2 or 5 successive days no tolerance
      developed. When animals were reused after 7 or 14 days SIH did not differ from
      day 1, implying that animals can be reused. When the number of mice was decreased
      from 10 to 5 mice per cage, the SIH of vehicle-treated mice was slightly lower in
      5-mice cages compared to 10-mice cages. The blocking effects on SIH by
      anxiolytics was also less clear in 5-mice cages compared to 10-mice
      cages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140154
TI  - Androgen regulation of adrenocorticotropin and corticosterone secretion in the
      male rat following novelty and foot shock stressors.
AB  - To examine mechanisms responsible for sex differences in hypothalamo-pituitary
      adrenal (HPA) axis responsiveness to stress, we studied the role of androgens in
      the regulation of the adrenocorticotropin (ACTH) and corticosterone (CORT)
      responses to foot shock and novelty stressors in gonadectomized (GDX) or intact
      male F344 rats. Foot shock or exposure to a novel open field increased plasma
      ACTH and CORT, which was significantly greater in GDX vs. intacts. Testosterone
      (T) or dihydrotestosterone propionate (DHT) treatment of GDX animals returned
      poststress levels of ACTH and CORT to intact levels. Estrogen treatment of GDX
      males further increased poststress CORT secretion above GDX levels. There was no
      difference in the ACTH response of anterior pituitaries from intact, GDX, and
      GDX+DHT animals to CRF using an in vitro perifusion system. There were no
      differences in beta max or binding affinity of type I or II CORT receptors in the
      hypothalamus or hippocampus of intact, GDX, or GDX+DHT groups. These data
      demonstrate an effect of GDX on hormonal indices of stress. The increased
      response in GDX rats appears to be due to the release from androgen receptor
      mediated inhibition of the HPA axis. This inhibition by androgen is not due to
      changes in anterior pituitary sensitivity to CRH, nor to changes in type I or
      type II corticosteroid receptor concentrations.

PMID- 8140155
TI  - Snake odor alters behavior, but not pain sensitivity in mice.
AB  - It is known that predator cues (both mammalian odor or avian vocalization) elicit
      marked analgesia in rodents. The present experiment used olfactory cues produced
      by an opportunistic rodent predator snake species (100 cc of sawdust scented by
      Elaphe quatuorlineata). Upon exposure to snake odor (for 30 s, 20 min, or 40
      min), adult mice of both the CD-1 and DBA2 strains were assessed for tail-flick
      or hot-plate analgesia at different times after exposure (from 0 to 40 or 45 min,
      respectively). In both strains, snake odor exposure induced significant
      alteration in the frequencies of sniffing, self-grooming, and digging, while it
      inhibited habituation of locomotor activity in DBA/2 mice. No analgesia emerged
      with both tests as a consequence of exposure to snake odor. Results suggest that
      although endogenous analgesia has been demonstrated by other authors to be
      elicited in response to cues emanating from common and widely distributed mouse
      predators (such as carnivores or owls), predators such as reptiles, which under
      natural conditions exert a limited predatory pressure on the house mouse gene
      pool, may only induce fear-associated behavioral responses but cannot provide
      ethologically relevant stimuli triggering mouse analgesia.

PMID- 8140156
TI  - Hormonal and behavioral responses of male hamsters to females and female odors:
      roles of olfaction, the vomeronasal system, and sexual experience.
AB  - Removal of the vomeronasal organ eliminated androgen surges in male hamsters in
      response to female vaginal secretions in both sexually experienced and sexually
      naive males; lesions of the olfactory mucosa had no effect on such responses.
      Both lesions led to deficits in behavioral responses to vaginal secretions. In
      response to interactions with estrous females, in contrast, lesions of either
      system alone had no influence on androgen surges in males (either sexually
      experienced or naive). Lesions of both systems, however, eliminated androgen
      surges in sexually naive males but not sexually experienced males. These dual
      lesions eliminated male mating behavior, while lesions of either system alone had
      little influence on mating. There were no significant correlations in any
      experiment between level of behavioral responses and degree of change in androgen
      levels. Thus, we conclude that the vomeronasal system mediates androgen surges in
      response to female odors but is not necessary for such responses to females
      themselves. In sexually naive males the vomeronasal and olfactory systems
      together are necessary for androgen responses to females. Behavioral responses
      were influenced by lesions and by sexual experience. Lesions of both systems
      increased the latency to investigate vaginal secretions, and sexual experience
      decreased the latency and increased the duration of investigation. Lesions and
      experience also influenced male sexual performance.

PMID- 8140157
TI  - Removal of the submaxillary salivary glands first increases and then abolishes
      the agonistic response of male mice in repeated social encounters.
AB  - Adult male mice of the CD-1 strain were sialectomized (bilateral removal of
      submaxillary salivary glands) under IP Nembutal anesthesia and then individually
      housed for 5 weeks. Control mice were sham operated. The behaviors of
      sialectomized and control mice towards untreated, intact, matched opponents were
      videotaped during the first 10 min of a 20-min social encounter repeated for 10
      consecutive days (isolation days 36-46). On the first session, sialectomized mice
      exhibited significant increases in elements of aggression (attack, bite,
      offensive sideways, offensive upright, and tail rattling). These behavioral
      changes significantly decreased over the remaining encounters, while defensive
      behaviors (defensive upright, oblique, parry, and defensive sideways) and
      elements of arrested flight increased progressively. The results suggest that
      sialectomy, perhaps by removing salivary NGF, interferes with the coping response
      of mice towards repeated agonist challenge from a conspecific.

PMID- 8140158
TI  - Intense sweeteners, food intake, and the weight of a body of evidence.
AB  - A review of published data shows that although intense sweeteners have been shown
      to increase hunger ratings in some studies in humans, this has not been a
      consistent and reproducible observation. Any slight effect on perceived hunger
      has not been translated into an increase in food ingestion or effects on blood
      concentrations of insulin or glucose. Studies on the covert substitution of
      caloric sweeteners by intense sweeteners have shown either a decrease or no
      change in body weight. The published database does not support the concept that
      the consumption of intense sweeteners results in a paradoxical increase in
      calorie intake and body weight.

PMID- 8140159
TI  - Microdialysis administration of vasopressin into the septum improves social
      recognition in Brattleboro rats.
AB  - The role of septal arginine vasopressin (AVP) in a social recognition test was
      investigated in both homozygous Brattleboro (HO-DI) and normal Long-Evans rats.
      To do this, the duration of investigation of conspecific juveniles by untreated
      adult males of both rat strains was measured before and after inter exposure
      intervals of 30 and 120 min. Additionally, a microdialysis administration
      technique was used to administer synthetic AVP (0.2 or 2.0 ng) or its V1 receptor
      antagonist d(CH2)5Tyr(Me)AVP (5.0 ng) into the mediolateral septum concomitantly
      with the behavioral test. Untreated HO-DI rats showed an impaired social
      recognition compared with untreated Long-Evans rats. A similarly impaired
      performance was observed after V1 receptor antagonist treatment of Long-Evans
      rats. Microdialysis administration of synthetic AVP, on the other hand,
      significantly improved social recognition in both rat strains. The data suggest
      that endogenous AVP in the septal brain area is critically involved in the
      acquisition, storage, and/or recall of olfactory cues in rats.

PMID- 8140160
TI  - Development of locomotion in the rat--spatiotemporal footfall patterns.
AB  - Footfall patterns during locomotor ontogeny have been observed in Wistar rats 10
      30 days old. These reveal that, even at 22 days, the paw contacts are both
      spatially and temporally unlike those of the adult. In the adult there is a
      precise presentation sequence involving early soft contact of tactile sensitive
      forepaw parts that may be important in tactile locomotor guidance and which is
      not fully established even at 22-30 days. The hindpaw contact pattern is also not
      yet adult-like involving a greater incidence of early toe contact. It is
      suggested that, only after day 15, when the forelimb is no longer the major
      weight-bearing limb, can it start to be developed for the fine discriminative
      touch required for tactile guidance of limb placement. Some further time is
      necessary for adult patterns to be achieved.

PMID- 8140161
TI  - The effects of intraventricular injection of beta-endorphin on initial estrogen
      action to induce lordosis behavior.
AB  - Ovariectomized female rats subcutaneously (SC) injected or intracerebrally
      implanted with estradiol benzoate (EB), and given progesterone SC were used as
      experimental animals to assess the effects of the beta-endorphin (beta-EP)
      neuronal system on lordosis behavior. In intraventricular (IV) injection of beta
      EP at the onset of sc EB priming, the lordosis behavior was significantly (p <
      0.001) facilitated. In contrast, the lordosis behavior was significantly (p <
      0.001) inhibited by IV injection of naloxone, an opioid receptor antagonist. beta
      EP facilitation of lordosis was observed exclusively within the initial stage of
      estrogen action. The behavior was significantly (p < 0.001) facilitated by IV
      injection of beta-EP given with an intracerebral implantation of crystalline EB
      into the septal-preoptic regions. However, the lordosis behavior was
      significantly (p < 0.001) inhibited by beta-EP when EB was implanted into the
      ventromedial hypothalamus. Animals receiving EB implants into the mesencephalic
      reticular formation were not affected by beta-EP. The present study suggests that
      the beta-EP neuronal system stimulates sexual receptivity through an action on
      the central nervous system in relation to the site of estrogen-initial activation
      to induce the lordosis reflex. The sites of beta-EP action may be the estrogen
      receptive septal-preoptic and hypothalamic regions; the former for facilitatory
      effect and the latter for inhibitory effect.

PMID- 8140162
TI  - Salt consumption and body fluid balance during cold exposure in rats.
AB  - We investigated the effect of exposure to cold on salt consumption and the role
      of salt consumption on the maintenance of body fluid balance in male Wistar rats.
      The rats were provided with both tap water and NaCl solution ad lib during 16-h
      exposure to cold (10 degrees C) and normal (25 degrees C) air temperature
      conditions. The concentration of the NaCl solution was 0.9% for one group (0.9%
      NaCl group; n = 7) and 1.8% for the other (1.8% NaCl group; n = 6). At 10 degrees
      C, weight loss was greater than that at 25 degrees C, and fluid and Na balance
      were negative in the 0.9% NaCl group. However, the calculated Na concentration of
      the fluid consumed in the 0.9% NaCl group was about 135 mEq/l Na (0.8% NaCl) at
      both 10 degrees C and 25 degrees C. In the 1.8% NaCl group, the values indicating
      fluid and Na balance under both temperature conditions were similar, while the
      calculated concentration of Na in fluid consumed at 10 degrees C (187 mEq/l Na:
      1.1% NaCl) was higher than that at 25 degrees C (153 mEq/l Na: 0.9% NaCl). These
      results suggest that the consumption of hypertonic NaCl solution indicating
      increased salt appetite during exposure to cold counteracts the loss of body
      fluid and Na via urine.

PMID- 8140163
TI  - Experimental study of the internal signal of alliesthesia induced by sweet
      molecules in rats.
AB  - To identify the preabsorptive signal that arouses alliesthesia, we compared the
      effects of five sweet molecules: glucose (3 g.5 ml-1), cyclamate (0.280 g.5 ml
      1), saccharin (0.016 g.5 ml-1), aspartame (0.020 g.5 ml-1), and mannitol (3 g.5
      ml-1) on the intestive aversive responses of rats. In Experiment 1, the sweet
      stimuli were adjusted to taste similarly sweet, and they were administered
      orally; they aroused similar ingestive responses. In Experiment 2, an
      isovolumetric load of each of the five molecules was administered in the stomach
      and its influence on ingestive/aversive response aroused by oral sucrose was
      recorded. Negative alliesthesia was obtained after gastric loads of glucose and
      mannitol, but not after gastric loads of cyclamate, saccharin, and aspartame.

PMID- 8140164
TI  - Effect of a novel CCKA receptor antagonist (2-NAP) on the reduction in food
      intake produced by CCK in pigs.
AB  - The effect of a novel CCKA receptor antagonist 2-naphthalene sulphonyl-L-aspartyl
      2-(phenethyl)amide, sodium salt (2-NAP) on the reduction of food intake induced
      by exogenous CCK, administered centrally or peripherally, has been examined in
      pigs. 2-NAP is hydrophilic and should not readily cross the blood-brain barrier.
      Intravenous (IV) 2-NAP (20 or 40 mg/kg) injected prior to IV CCK-8S (1
      microgram/kg) abolished the inhibitory effect of CCK-8S on operant food intake in
      hungry pigs. Intravenous injections of 2-NAP (20 and 30 mg/kg) prior to the
      administration of intracerebroventricular (ICV) injection of CCK-8S (1 microgram)
      did not affect the inhibitory action of ICV CCK-8S on food intake. ICV injection
      of 2-NAP (5 mg) abolished the inhibitory effect on food intake of ICV CCK-8S (1
      microgram). The results indicate that 2-NAP does not cross the blood-brain
      barrier readily and that central and peripheral administration of CCK-8S inhibits
      feeding by different mechanisms. Neither ICV nor IV injection of 2-NAP altered
      food intake when injected alone.

PMID- 8140165
TI  - Evidence for the involvement of prolactin in the maternal behavior of the
      hamster.
AB  - The hormonal basis of maternal behavior in the hamster has not been clearly
      established. Treatment of parturient females on the day of delivery with the
      prolactin release inhibitor, bromocriptine, resulted in a significant disruption
      of maternal responsiveness at doses as low as 0.5 mg When pregnant females were
      implanted with ectopic pituitary grafts under the kidney capsule on day 8 or 9 of
      gestation to elevate circulating prolactin levels, there was no disruption of
      maternal behavior after bromocriptine injection on the day of delivery. Taken
      together, these data indicate that prolactin may be an important modulator of the
      natural onset of maternal behavior at parturition in the hamster.

PMID- 8140166
TI  - Early exposure to low levels of estradiol (E2) mitigates E2-induced conditioned
      taste aversions in prepubertally ovariectomized female rats.
AB  - 17 beta-Estradiol (E2) can serve as a potent unconditioned stimulus in producing
      a conditioned taste aversion to saccharin in rats, with the effect being greater
      in males than in females. To determine whether the female's lower susceptibility
      to such conditioning is due, in part, to early experience with estrogen, we
      performed the following experiment. First, we pretreated groups of prepubertally
      ovariectomized female rats with either sesame oil (control group) or low doses of
      E2 (0.3, 0.75, or 1.50 microgram). Second, in subsequent conditioning sessions,
      we presented a 0.2% saccharin solution to the rats prior to the injection of 100
      micrograms of E2 (the unconditioned stimulus). Third, we tested the magnitude of
      the conditioned aversion to the saccharin solution and its tendency to extinguish
      during the following week. The E2-pretreated animals evidenced significantly
      weaker taste aversions and extinguished them more rapidly than did the oil
      pretreated controls, even at the lowest E2 pretreatment dose, suggesting that
      prior experience with low levels of estrogen can significantly mitigate, in
      female rats, the magnitude of a conditioned taste aversion produced by a high
      dose of estrogen.

PMID- 8140167
TI  - "Cohort removal" induces hyperthermia but fails to influence plus-maze behaviour
      in male mice.
AB  - Mice removed last from their home cage display elevated body temperature compared
      with those removed first. This stress-induced hyperthermia (SIH) response has
      been reported for Swiss and NMRI mice and has been forwarded as a model of
      anticipatory anxiety. In the present study, the effects of order of removal from
      the home cage (cohort removal) on body temperature and behaviour in the elevated
      plus maze have been examined in group-housed male DBA/2 mice. Results confirm the
      basic phenomenon of SIH in this strain, with mice removed from the home cage in
      positions 4-10 displaying a significantly higher mean rectal temperature compared
      with those removed in positions 1-3. Despite this observation, however, detailed
      ethological analysis failed to reveal any significant effect of cohort removal on
      behaviour displayed in the elevated plus-maze paradigm. Data are discussed in
      relation to variations in the nature of reactions evoked in different animal
      models of anxiety.

PMID- 8140168
TI  - Menstrual cycle and sex differences influence salt preference.
AB  - Previous studies demonstrate that some women have a greater preference for
      palatable high-sugar and high-fat foods premenstrually. Because salt may also be
      considered palatable, it was of interest to discover whether salt preference also
      varies. To determine whether there are differences in salt preference across the
      menstrual cycle, 49 women and 31 men rated popcorn sprayed with five different
      concentrations (0M, 1M, 2M, 3M, 3M+) of salt solution. Between-subjects
      comparisons of women revealed that those tested in separate weeks of their
      menstrual cycle had differing preferences for salt. Specifically, women in their
      luteal week preferred unsalted popcorn (0M) significantly less than women tested
      during their ovulatory or follicular weeks. Women in the menstrual week also
      tended to find the saltiest popcorn (3M+) much less palatable than women tested
      in their follicular, luteal, or ovulatory weeks. When men's and women's
      preference ratings of the same stimuli were compared, an overall sex difference
      was found. Men liked the mildly salty popcorn (2M) more than women. There were no
      significant differences in perceived saltiness ratings between men and women or
      among women tested in different weeks of their cycle.

PMID- 8140169
TI  - The activity of rats in a swimming situation as a function of water temperature.
AB  - Previous research has shown that time before drowning in rats decreases gradually
      as stress is increased by varying water temperature in the swimming situation. In
      the present research, the activity of swimming rats appeared to be a U function
      of varying water temperature, lending support to the notion that activity is a
      behavioral measure that estimates the rats chances of survival in the water. This
      conclusion was further supported by the covariation of activity with a different
      behavioral measure of survival. In addition, activity during sessions decreased
      gradually, suggesting that a lowered activity is an adaptive response in the rat.
      Activity, thus, appears to be negatively correlated to the rat's survival chances
      under colder (14-23 degrees) and warmer (23-47 degrees) temperatures; i.e., in a
      more stressful situation, including extreme fear. It may be, therefore, that a
      decrease in activity obtained in present laboratory models (i.e., immobility) is
      more relevant to the extinction of fear than despair, as reported by other
      researchers.

PMID- 8140170
TI  - Adrenal role in proceptivity and receptivity induced by two modes of estradiol
      treatment.
AB  - The effects of chronic estrogen treatment on the receptive and proceptive
      behaviors of the female rat were investigated using two modes of estrogen
      administration: estrogen implants and chronic estrogen injections. In addition,
      the potential mediating role of the adrenal was investigated. Animals were either
      ovariectomized (OVX) or ovariectomized and adrenalectomized (ADX-OVX). Each
      surgery group received three doses of estrogen, via implants in Experiment 1 and
      chronic injections in Experiment 2. Each animal was tested with and without
      progesterone treatment. Within the range of doses in the two experiments, the
      effect of estrogen on proceptivity appeared to be dose dependent. However, low
      estrogen doses were sufficient to maintain a high level of receptivity. These
      results suggest different mechanisms for the induction of proceptive and
      receptive behavior in the female rat. The facilitatory effect of progesterone on
      receptivity was dependent on the estrogen dose for both modes of administration,
      but on proceptivity was dependent on the estrogen dose only following chronic
      estrogen injections. Overall, this study suggests that the adrenal gland is
      important in the display of female sexual behavior elicited by exogenous
      hormones. The estrogen implant study (Experiment 1) revealed that while the
      adrenal gland is not necessary for receptive behavior, it is important for the
      display of proceptive behavior. In addition, with chronic estrogen injections
      (Experiment 2), progesterone was more effective in elevating proceptivity in ADX
      OVX than in OVX females, and ADX-OVX females treated with progesterone generally
      showed less lordosis behavior than OVX females treated with progesterone. These
      results suggest that progesterone of adrenal origin may be important for sexual
      responding in the female rat.

PMID- 8140171
TI  - Estrogen antibodies reduce vulnerability to stress-induced failure of
      intrauterine implantation in inseminated mice.
AB  - In Experiment 1, inseminated mice were randomly assigned to either an undisturbed
      control condition or four conditions involving exposure to restraint stress on
      days 1 through 5 of pregnancy. Restrained animals received one of three doses of
      estrogen antibodies or just vehicle injections on each day of restraint.
      Restrained animals receiving vehicle only showed significantly fewer uterine
      implantation sites than did unrestrained controls, while restrained animals given
      estrogen antibodies showed more implantation sites than did vehicle-treated
      restrained animals. In Experiment 2, varied dosages of refined estrogen
      antibodies were administered to inseminated females concurrent to restraint
      stress on days 1 through 5 of pregnancy. More females receiving the higher
      dosages of antibodies produced litters than did restrained females with just
      vehicle injections, and at the highest dose the number of litters was similar to
      that produced by undisturbed control females. These results converge with other
      evidence to suggest that stress-induced pregnancy blocks are mediated by
      estrogens.

PMID- 8140172
TI  - Individual behavioral and physiological strategies in pigs.
AB  - Previous experiments demonstrated consistent individual behavioral differences in
      pigs. Some showed a more active behavioral response (so-called A/R pigs), others
      a more passive behavioral response (so-called NA/NR pigs). In the present study
      we selected 32 A/R and 32 NA/NR individuals and tested them individually in an
      open field at 3 (OF1) and 8 weeks of age (OF2). Individual response patterns were
      remarkably consistent between OF1 and OF2. While more A/R than NA/NR pigs made
      escape attempts, the A/R ones vocalized less, and were less inhibited to approach
      novel objects in OF1 and OF2, although they spent less time in exploring these
      objects than NA/NR pigs. Cortisol (CS) level after OF1 increased in A/R pigs but
      did not change in NA/NR ones, while CS level in OF2 remained constant in A/R pigs
      but decreased in NA/NR pigs. CS response to ACTH1-39 was measured at 3 and 8
      weeks of age but did not differ between types. Basal CS level was higher in NA/NR
      than in A/R pigs and accompanied by adrenal hypertrophy. Mean heart rate (HR) was
      higher of A/R pigs compared to NA/NR ones in two backtests. HR of A/R pigs
      substantially increased (23.9 bpm = 15.5%) in reaction to the novel object in
      OF2, while HR of NA/NR ones only slightly increased (4.5 bpm = 2.9%), or even
      decreased (bradycardia). A/R pigs had more often heart deviations than NA/NR
      ones. The present study demonstrates that the two behavioral strategies of pigs
      are characterized by consistent differences in behavioral, physiological, and
      endocrine responses to conflict situations.

PMID- 8140173
TI  - A new operant discrimination test procedure for resident rats.
AB  - An automated method for testing visual discrimination with water reinforcement
      using a modified residential Y-maze is described. The visual stimulus is
      presented above one of two water holes. Rats have been tested with different
      lengths of water periods and different intervals between the periods. During the
      10 days of testing, overall activity decreased. Activity on the initial days was
      low during daytime, with few drinking attempts. Discrimination learning
      acquisition was measured as the increase in the percentage of water periods with
      drinking attempts in which the first attempt occurred on the correct side, and/or
      as the increase in the number of correct drinking attempts as a percentage of all
      drinking attempts. Acquisition was observed both when light indicated water and
      when it indicated no water. This test model may offer a useful method for
      standardized measurement of left/right, light on/off discriminations.

PMID- 8140174
TI  - Effect of nicotine on sympathetic nervous system activity of mice subjected to
      immobilization stress.
AB  - We tested the hypothesis that nicotine possesses an antistress action by
      measuring the turnover of norepinephrine (NE), a reliable indicator of
      sympathetic nervous system activity, in the interscapular brown adipose tissue
      (IBAT) and heart of mice treated with nicotine injections, immobilization stress,
      or nicotine + immobilization stress, vs. untreated controls. Nicotine enhanced
      the sympathetic activity in the IBAT and heart, and induced a loss of body
      weight. Immobilization-related stress accelerated sympathetic activity in the
      IBAT and heart more strongly than did nicotine loading alone. Pretreatment with
      nicotine suppressed the sympathetic activity induced by immobilization stress to
      the same extent as that observed after administering nicotine alone. Thus, these
      results appeared to support our hypothesis.

PMID- 8140175
TI  - Blood pressure responses to acute exercise in type A females.
AB  - Cardiovascular responses to moderate steady state exercise were studied in type A
      females. Twenty-one women, ages 18 to 43 years (mean 29.7 +/- 2.0), were divided
      into type A (n = 11) and type B (n = 10) groups by means of the Jenkins Activity
      Survey (JAS). Baseline measurement included EMG, BP, and psychometric data.
      Subjects exercised on a treadmill at 60% VO2 peak for 20 min. Postexercise
      systolic and diastolic BP (SBP, DBP) reductions were similar in the type A and
      type B groups [111/72 to 104/66 and 108/70 to 98/62 mmHg, respectively, (F(1, 38)
      = 4.03, p < 0.05]. However, DBP responses during exercise for type B, but not the
      type A, were lower [71 +/- 2 to 60 +/- 2 mmHg, preexercise to steady state
      exercise, (F(1, 38) = 7.14, p < 0.01]. Also, steady state exercise SBP was lower
      in type B compared to type A [159 +/- 3 vs. 150 +/- 4 mmHg, (F(1, 38) = 3.97, p <
      0.05]. These data with psychometric data, suggest that hemodynamic and other
      physiological responses to exercise in females vary according to behavioral types
      associated with differing physiology.

PMID- 8140176
TI  - Bombesin acts to suppress feeding behavior and alter serum growth hormone in
      goldfish.
AB  - The acute effects of a single injection of bombesin (BBS) on feeding behavior and
      serum growth hormone (GH) levels in goldfish were examined. When injected
      intraperitoneally (IP), BBS (0.5-100 ng/g) caused a dose-dependent decrease in
      food intake within 30 and 45 min of administration; maximal suppression was
      achieved at 50 ng/g BBS and was accompanied by an elevation in serum GH levels.
      Associated with IP injection of BBS was a pronounced spitting out behavior in
      which food pellets were taken into the oral cavity but immediately expelled. When
      injected into goldfish deprived of food for 72 h, 50 ng/g BBS was still potent in
      suppressing feeding behavior and increasing serum GH. Additionally, IP injection
      of BBS (10 or 100 ng/g) into groups of fish caused a significant increase in
      circulating serum GH levels at 1.5 h postinjection. Finally, when injected into
      the third brain ventricle (ICV), 60 ng/g BBS also caused a suppression in food
      intake and a concomitant increase in serum GH. Groups of fish injected ICV with 5
      or 50 ng/g BBS also exhibited a graded increase in serum GH levels at 45 min
      postinjection. Overall, these data are the first to demonstrate in any lower
      vertebrate that a neuropeptide acts to suppress food intake and cause concomitant
      alterations in circulating serum GH levels, following either peripheral or
      central administration.

PMID- 8140177
TI  - Time course for synchronization of spontaneous locomotor activity in the rat
      following reversal of the daylight (12:12 h) cycle.
AB  - The present results demonstrate that 5-7 days on a reversed light-dark cycle
      (12:12 h) is sufficient for the synchronization of spontaneous locomotor activity
      with the new circadian rhythm in rats. Once established, the circadian rhythm is
      stable for at least 3 days under constant illumination conditions. Reversal of
      the light-dark cycle appears to be both a reliable and practical procedure in
      everyday laboratory work.

PMID- 8140178
TI  - Physiological correlates of attenuated salt appetite in Fischer 344 rats.
AB  - Dietary NaCl deprivation stimulates a robust salt appetite in Wistar rats but has
      little influence on this behavior in rats of the Fischer 344 (F344) strain. To
      examine physiological substrates of attenuated salt appetite in F344 rats,
      several pertinent measures of renal function and fluid homeostasis were made in
      Wistar and F344 rats eating normal and NaCl-deplete diets. Physiological
      adjustments to NaCl deprivation were similar between the two strains; however,
      F344 rats showed smaller increases in plasma renin activity (PRA) than their
      Wistar counterparts. In addition, F344s decreased urinary sodium excretion more
      rapidly than Wistar rats in response to deprivation. The present studies also
      revealed several strain differences in baseline fluid and electrolyte regulation.
      Relative to the Wistar strain, F344 rats were characterized by high baseline PRA,
      increased arginine vasopressin (AVP) excretion, decreased urine volume, and
      diminished thirst. We propose that AVP and oxytocin activation may reduce salt
      preference and suppress the development of salt appetite in F344 rats.

PMID- 8140179
TI  - Within-session changes in peak N160 amplitude of flash evoked potentials in rats.
AB  - The negative peak occurring approximately 160 ms after stimulation (peak N160) of
      flash evoked potentials (FEPs) of rats changes with repeated testing.
      Habituation, sensitization, and arousal have all been invoked to explain these
      changes, but few studies have directly tested these explanations. We examined
      within-session changes in peak N160 amplitude with repeated testing, and the
      modulatory effects of stimulus intensity and auditory white noise. Peak N160
      amplitude increased with daily testing (between-session changes), and was larger
      at greater stimulus intensities. In contrast, peak N160 amplitude underwent
      within-session increases on early days and within-session decreases on later
      days. The within-session changes were not affected by stimulus intensity. In rats
      previously tested in a quiet environment, exposure to acoustic white noise
      increased motor activity and transiently decreased peak N160 amplitude, which
      then increased and subsequently decreased with continued photic and acoustic
      stimulation. Repeated testing in the presence of noise did not alter the within
      session changes in peak N160 amplitude. Heart rate showed both within- and
      between-session decreases, but was unaffected by noise. The data suggest that the
      within-session changes in peak N160 amplitude may reflect a habituation-like
      response to the test environment.

PMID- 8140180
TI  - Normalization of auditory sensory gating in schizophrenic patients after a brief
      period for sleep.
AB  - Diminished suppression of the P50 component of the evoked potential following
      repeated auditory stimuli is one example of a deficit in elementary sensory
      processing in schizophrenia. Normal subjects suppress the P50 evoked potential to
      the second of two paired auditory stimuli. Although normal P50 suppression is
      occasionally observed in schizophrenic patients, it generally disappears with
      subsequent testing. The object of this experiment was to determine conditions for
      the reproducible normalization of P50 suppression in schizophrenic patients.
      After baseline recordings, 12 schizophrenic subjects were allowed to sleep for 10
      minutes. The depth of sleep obtained was assessed by electroencephalography
      (EEG). Normalization of P50 suppression was observed for approximately 3 minutes
      in all subjects who entered slow wave sleep, but not in those whose EEG records
      remained desynchronized. Some change was even observed in subjects who had only
      persistent alpha waves. The amount of normalization was correlated with the
      deepest stage of sleep reached. Normal control subjects did not show this
      phenomenon but instead had a transient decrease in sensory gating after waking
      from sleep. The results suggest that schizophrenic patients may have a defect
      that causes a neuronal mechanism critical to sensory gating to fail after brief
      use, although its activity can be transiently restored by a short period of
      inactivity. A rapidly desensitized neurotransmitter receptor is one possible
      mechanism of such an effect.

PMID- 8140181
TI  - A topographical study of senile plaques and neurofibrillary tangles in the
      hippocampi of patients with Alzheimer's disease and cognitively impaired patients
      with schizophrenia.
AB  - Neuropsychological testing of elderly schizophrenic patients reveals that a
      significant portion of this population exhibit varying degrees of cognitive
      impairment. Since Alzheimer's disease is the most common cause of dementia in
      geriatric patients, we investigated whether the cognitive decline observed in
      schizophrenia is the result of degenerative changes analogous to those
      characteristic of Alzheimer's disease. For this purpose, the number and
      distribution of senile plaques and neurofibrillary tangles were mapped in the
      hippocampi of 10 cognitively impaired schizophrenic patients, 10 patients with
      Alzheimer's disease, and 10 patients with dementia not attributed to either
      schizophrenia or Alzheimer's disease. In Alzheimer's disease, degenerative
      changes invariably predominated in the CA1 subfield, subiculum, and proisocortex.
      By contrast, findings characteristic of Alzheimer's disease were virtually never
      observed in the hippocampi of schizophrenic and other cognitively impaired
      patients. In some patients with Alzheimer's disease, the presence of senile
      plaques in the molecular layer of the dentate gyrus suggested the existence of an
      underlying entorhinal cortex lesion. Similar dentate gyrus pathology was never
      found in any of the other patients. The authors conclude that cognitive
      impairment in schizophrenia is not the result of degenerative changes analogous
      to those found in Alzheimer's disease.

PMID- 8140182
TI  - Exposure therapy, fluvoxamine, or combination treatment in obsessive-compulsive
      disorder: one-year followup.
AB  - Sixty outpatients with obsessive-compulsive disorder (OCD, 22 men, 38 women) were
      randomized to receive 6 months of antiexposure therapy with fluvoxamine (group
      F), exposure therapy with fluvoxamine (group Fe), or exposure therapy with
      placebo (group Pe). Patients in group F did not comply with antiexposure therapy,
      so it was in fact a neutral condition. Patients began with depressed mood (mean
      Hamilton depression score = 19). Fifty patients were reevaluated at week 8, 44 at
      week 24 (posttest), 37 at week 48, and 33 at 18 months, 1 year posttreatment
      (group F, n = 10; group Fe, n = 12; group Pe, n = 11). The three groups improved
      on rituals and depression. There was a drug effect on rituals at week 8 and on
      depression at week 24; both these effects disappeared at week 48. The 33 18-month
      completers had been comparable at baseline to those not followed up, apart from
      having more severe behavioral avoidance. At 18-month followup, patients as a
      whole remained improved with no between-group differences; over 80% of the Fe and
      Pe patients versus 40% of the F patients were not receiving antidepressant
      treatment (Fe vs. F: p < 0.04; Pe vs. F: p = 0.053; Fe vs. Pe: NS). In OCD
      fluvoxamine and exposure therapy were synergistic in the short term, and exposure
      reduced subsequent need for antidepressants in the followup year after they had
      been stopped.

PMID- 8140183
TI  - Seasonal mood changes in 250 normal women.
AB  - A 1-year prospective study of seasonal mood changes was conducted in 250 female
      Boston area residents, aged 43 to 72, who were participants in a study of vitamin
      D supplementation. Each woman completed the Profile of Mood States questionnaire
      at four study visits. There were significant changes over the year in scores for
      Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue-Inertia, and
      Confusion-Bewilderment. These scores were all highest or "worst" in the fall and
      lowest in the spring or summer. Worse mood scores were associated with fewer
      hours of sleep. Serum thyroxine was positively associated with higher Depression
      Dejection scores in August through November and with higher (better) Vigor
      Activity scores in February through May. Supplementation with 400 IU of vitamin D
      did not appear to affect levels or changes in mood scores.

PMID- 8140184
TI  - Erythrocyte membrane phospholipids in psychotic patients.
AB  - Thin layer chromatography and laser densitometry were used to examine erythrocyte
      membrane phospholipid composition in 13 medication-free patients with
      schizophrenia or schizoaffective disorder and 11 healthy control subjects. The
      patient group had significantly decreased levels of phosphatidylethanolamine and
      a significant increase in sphingomyelin. The patient group also showed a trend
      toward decreased levels of phosphatidylinositol bisphosphate. Levels of
      phosphatidylcholine and lysophosphatidylcholine did not significantly differ
      between groups. There were no significant effects of age, body mass index, or
      gender on any of the phospholipid parameters. The observed alterations may point
      to abnormalities in key membrane-related functions, including signal transduction
      and ion transport.

PMID- 8140185
TI  - Confidence interval of the kappa coefficient by bootstrap resampling.

PMID- 8140186
TI  - Psychiatric aspects of organ transplantation in children and adolescents.
AB  - Organ transplantation has become the treatment of choice for a number of life
      threatening childhood illnesses. This article explores four psychiatric issues
      raised by pediatric transplantation: 1) the role of the family, 2) the context of
      the illness, 3) developmental issues, and 4) long-term effects. The effects of
      these issues on children before, during, and after the transplant hospitalization
      are reviewed, with suggestions for clinicians and researchers working in this
      challenging new area.

PMID- 8140187
TI  - Management of lithium in patients with cancer.
AB  - This article reviews the management of lithium in patients who require optimum
      management of cancer and simultaneous prevention of mania or depression in
      lithium-sensitive affective illness. Two cases are described. Discussion focuses
      on whether lithium should be continued during chemotherapy and radiation
      treatment, the complications that would lead to lithium toxicity in an otherwise
      stable patient, the likely settings for hypothyroidism, and the role of lithium
      to stabilize steroid-induced affective changes. The authors conclude that lithium
      may be withheld 1 or 2 days before cytotoxic chemotherapy and restarted when the
      patient is able to drink. It may be given as usual through routine radiation
      treatment, but it should be discontinued during cranial radiation. Calcium,
      renal, cardiac, and thyroid functions should be monitored.

PMID- 8140188
TI  - Patient attitudes and psychological considerations in dialysis discontinuation.
AB  - The authors surveyed 36 adult patients who were maintained with chronic renal
      dialysis concerning their attitudes about dialysis discontinuation. Few subjects
      reported having ever considered stopping the life-support treatment. When asked
      to consider 12 hypothetical scenarios in which they might consider stopping
      treatment (e.g., onset of dementia or blindness), most subjects would still not
      consider discontinuation. Consideration of dialysis discontinuation was directly
      correlated with the patient's educational level. Follow-up after 1 year
      underscored the substantial differences between the responses the subjects gave
      to the 12 hypothetical scenarios and their real-life responses when they were
      later faced with decisions to actually terminate treatment. Psychiatrists have an
      opportunity to participate in the complex clinical and ethical decisions
      associated with advance directives and patients' right to refuse life-support
      treatment.

PMID- 8140189
TI  - Pediatricians' perceptions of child psychiatry consultations.
AB  - To ascertain pediatrician's expectations of child psychiatric consultants at our
      facility, a self-report questionnaire was sent to the 135 members of the
      Department of Pediatrics, The University of Florida Health Science Center, in
      1991. The 73 respondents (54%) reported high rates of emotional problems and
      adverse family situations in their patients, and a majority said they used
      psychiatric consultation sometimes or often. Adolescents were the patient group
      most frequently referred, and behavioral problems were the most frequent reasons
      for consultation requests. Pediatricians most valued a timely response and
      accessibility from consultants. These results are discussed with reference to the
      further development of a consultation-liaison service within a child and
      adolescent psychiatry training program.

PMID- 8140190
TI  - Psychiatric and medical factors associated with disability in patients with
      dizziness.
AB  - Dizziness is a common patient symptom and often remains medically unexplained
      even after an extensive work-up. The otologic disorders, psychiatric disorders,
      and functional disability of 75 patients presenting with dizziness to a community
      otolaryngology practice were assessed in 1991. The patients were classified
      according to the presence or absence of at least one current DSM-III-R
      psychiatric disorder and the presence or absence of a peripheral vestibular
      disorder. Decrements in mental health and role functioning, and increases in
      bodily pain and hypochondriacal focus were significantly associated with the
      presence of a psychiatric disorder and whether the etiology of dizziness was due
      to a peripheral vestibular dysfunction.

PMID- 8140191
TI  - Anxiety in experimentally induced somatoform symptoms.
AB  - This study examined the anxiety and pain reports in a group of subjects during a
      stimulation experiment in which the subjects were misinformed that an electrical
      current was being conducted through electrodes attached to their heads. The
      experiment's purpose was to determine how the subjects' reporting of pain was
      related to their reporting of anxiety over time. One subset of the subjects rated
      pain only, a second rated pain and anxiety, and a third rated pain and hunger.
      The three groups did not differ significantly in the frequency or intensity of
      their pain reports. The separate ratings for both anxiety and pain increased in a
      parallel manner. These results, however, do not support the theories involving
      the suppression of awareness of affect in somatofom disorders.

PMID- 8140192
TI  - A screening test for subtle cognitive impairment early in the course of HIV
      infection.
AB  - The authors report on the use of the Rey-Osterrieth Complex Figure Copy (ROC) and
      Memory (ROM) test as a bedside screening measure of cognitive impairment in 67
      HIV-seropositive persons (43 men, 24 women). HIV-seropositive individuals scored
      significantly worse than 49 HIV-seronegative matched individuals (33 men, 16
      women) in the control group on the ROC (P = 0.045, effect size = 0.39), but not
      on the ROM test. The scores did not correlate with stage of HIV infection, CD4a
      cell counts, cerebrospinal fluid parameters, or measures of affective state. No
      gender effects on performance were noted. It is concluded that while cognitive
      deficits may occur early in asymptomatic HIV disease, the ROC/ROM test as the
      authors used it is not a useful screening tool for clinicians. The study also
      suggests that the growing number of HIV-positive women should be included in
      neuropsychological studies of early HIV disease.

PMID- 8140193
TI  - Porphyria and panic disorder with agoraphobia.

PMID- 8140194
TI  - Intravenous lorazepam in the treatment of postictal psychosis.

PMID- 8140195
TI  - Pimozide is effective in delirium secondary to hypercalcemia when other
      neuroleptics fail.

PMID- 8140196
TI  - A significant increase in lithium levels after concomitant ACE inhibitor
      administration.

PMID- 8140197
TI  - Amyotrophic lateral sclerosis presenting with psychosis.

PMID- 8140198
TI  - Is there a risk for dependency with therapeutic doses of dimenhydrinate?

PMID- 8140199
TI  - Treatment of aggression in juvenile-onset Huntington's disease with buspirone.

PMID- 8140200
TI  - Serotonergic agents in the management of dementia and posttraumatic stress
      disorder.

PMID- 8140201
TI  - Functional psychoses is the concept disintegrating?

PMID- 8140202
TI  - Controlled release of theophylline from inert matrices: effect of channeling
      material on release rate.
AB  - Sustained release theophylline tablets containing stearic acid wax and lactose
      fast flo as chanelling agent were prepared and evaluated. The fusion technique
      was used for dispersing the drug in the different levels of stearic acid. The
      release rate of theophylline from the prepared tablets increased with the
      increase of the level of the channeling material in the formula. The drug release
      from tablets containing high level of wax (30 and 60%) and low level of
      channeling material (59% and 29%) followed the diffusion controlled model for
      inert porous matrix. The drug release increased significantly with the increase
      of lactose fast flow level in the formula. After 2 hours of testing dissolution,
      the tablets start to erode and the mechanism of drug release deviate from the
      diffusion controlled model. The mechanism of drug release was dependent on the
      level of the channeling material in the matrix.

PMID- 8140203
TI  - Endemic plants of Puerto Rico: brine shrimp lethality and antibacterial activity.
AB  - A total of 49 endemic plants of Puerto Rico were evaluated for their
      toxicological and antibacterial activities. The toxicological analysis was
      conducted with brine shrimp (Artemia salina Leach) lethality bioassay and the
      antibacterial screening was carried out by means of the agar diffusion test. In
      the toxicological bioassay, six plant extracts showed LC-50 values below 200
      g/ml., indicating the potential presence of bioactive compounds. In the
      antibacterial screening, over 80% of the plant extracts displayed activity
      against gram positive bacteria, whereas only 6% of the extracts inhibited the
      growth of the gram negative bacteria.

PMID- 8140204
TI  - Sustained release phenylpropanolamine hydrochloride from ATO 888 matrix.
AB  - Sustained release phenylpropanolamine HCl tablets were prepared with compritol as
      a retardant material. The effects of varying wax levels and methods of matrix
      formation on drug release were investigated. Also the compaction profiles were
      recorded for all formulations. The amount of drug in the formula was held
      constant (10% w/w), while the wax level was varied from 10% to 50% w/w. Two
      methods were used for the preparation of drug: wax systems; physical mixture and
      solid dispersion. The drug release from tablets containing 10% Compritol and
      prepared by solid dispersion was 97% after six hours of testing dissolution.
      Tablets prepared with 30% wax released 72% of the drug, while tablets containing
      50% wax released only 30% of the drug after six hours. Tablets prepared by
      physical mixture gave higher drug release than tablets prepared by solid
      dispersion method. The incorporation of Compritol decreased the ejection forces
      of tablets during compaction. The drug release from tablets prepared by solid
      dispersion followed the diffusion controlled model described by Higuchi for inert
      porous matrix.

PMID- 8140205
TI  - Acetaminophen-alginate spheres prepared by cross linking technology.
AB  - Spheres of acetaminophen (APAP) were prepared via the cross linking agglomeration
      technique and were successfully compacted into tablets. The drug load in all
      formulations was 20% w/v, the cross linking agent varied from 1% w/v to 20% w/v,
      the polymer levels varied from 1% w/v to 4% w/v and the residence time from 3 to
      60 minutes. The data obtained showed that increasing the concentration of the
      cross linking agent to 5% w/v or more showed no reduction in drug release rate.
      Also varying the residence time of the spheres in the cross linking solution
      showed no detectable differences in the drug release from spheres. Formulations
      prepared with 3% w/v and or 4% w/v polymer level showed higher drug release than
      formulation prepared with lower polymer levels.

PMID- 8140206
TI  - Physicochemical characterization of acetaminophen-ethylcellulose solid
      dispersion.
AB  - In this study, ethylcellulose was evaluated as a carrier for the preparation of
      sustained release of acetaminophen via solid dispersion technique. Physical
      mixture at the same level of acetaminophen and ethylcellulose was prepared.
      Differential scanning calorimetry and scanning electron microscope were used to
      characterize the physical properties of the various systems and to determine if
      there is possible interaction between acetaminophen and ethylcellulose.

PMID- 8140207
TI  - Multifunctional immunological monitoring of HIV positive patients: a novel
      staging system.
AB  - A tri-functional in vitro evaluation has been utilized to analyze peripheral
      blood mononuclear cells (BMNC) from HIV-infected patients, which allows for the
      classification of these individuals into convenient stages, according to the
      number of in vitro parameters affected. The classifying functional parameters
      are: the mitochondrial metabolic activity of freshly isolated BMNC, measured by
      an MTT reduction assay, the detection of apoptosis in 72 hour cultures of these
      cells assessed by propidium iodide staining and dual parametric flow cytometric
      analysis, and their proliferative response to pokeweed mitogen. Our results
      indicate that HIV-infected patients at different stages of their clinical
      disease, can present dysfunctions in one, two or three of the above-mentioned
      parameters. Based on these results, patients can be classified into four newly
      described stages which are Stage 0, including uninfected controls and all
      patients with unaffected parameters, and Stages 1, 2 and 3, including patients
      having one, two or all three parameters affected, respectively. This type of
      immunological evaluation and classification of HIV-infected patients has the
      potential of becoming a predictive tool in the longitudinal follow-up of their
      HIV infection.

PMID- 8140208
TI  - Idiopathic hemochromatosis: a study in a large Puerto Rican family.
AB  - We studied 13 first-degree relatives in a large family with an index case of
      idiopathic hemochromatosis to detect the relatives with evidence of iron
      overloading. Serum iron, total iron binding capacity (TIBC), and serum ferritin
      levels were measured in all family members. We also performed HLA typing to
      identify the relatives who are homozygous with the proband and genetically
      predisposed to develop the disease. The family was composed of the parents and 12
      siblings including the index case. The mean age of the siblings was 25 years.
      None presented with evidence of iron overload by the iron biochemical tests. HLA
      typing demonstrated six homozygous siblings with the proband. In separate
      analysis these siblings did not present abnormalities in any of the iron
      biochemical tests. These homozygous relatives were followed for one year after
      initial evaluation and none presented abnormalities in the iron studies during
      this period. These results are contradictory to other previous studies done in
      families with idiopathic hemochromatosis. The most feasible explanations for
      these findings are the young age of these siblings and the predominance of
      females among them. We consider that these homozygous relatives must be followed
      for their life-times with iron studies to detect a possible increase in iron
      stores as expected in later ages.

PMID- 8140209
TI  - Epidemiological study of tinea capitis in Puerto Rico.
AB  - Two separate studies were carried out to determine the dermatophytes responsible
      for tinea capitis in Puerto Rico. A retrospective study to determine those agents
      during the period between 1979 and 1989 revealed a total of 36 mycologically
      positive cases. The causative organisms consisted of the following species: M.
      canis, 14 cases (38.9%); T. mentagrophytes, 7 cases (19.4%); T. rubrum, 7 cases
      (19.4%); M. gypseum, 5 cases (13.9%); and T. tonsurans, T. verrucosum,
      unclassified Microsporum species, 1 case each (2.8% each). In a prospective
      study, fungal cultures were obtained from the scalps of 95 randomly selected
      children (45 males, 50 females) seen at the outpatient dermatology clinics of the
      Medical Sciences Campus of the University of Puerto Rico for a variety of skin
      problems but with no symptoms or signs of disease. One culture was positive for
      M. canis. All other cultures were negative. The significance of these findings is
      discussed as well as their relation to the incidence of T. tonsurans scalp
      infections in the Unites States.

PMID- 8140210
TI  - Identification of Streptococcus mutans from human dental plaque using the RapID
      STR System.
AB  - The identification of Streptococcus mutans from dental plaque samples with rapid
      systems, such as the RapID STR System, has not been recommended by the
      manufacturers. In this study, we evaluated the use of the above method for the
      identification of 34 human dental plaque Streptococcus mutans strains which had
      been identified previously by conventional procedures. The results obtained
      demonstrate that 88.2% of the Streptococcus mutans strains tested were
      identifiable by the rapid method.

PMID- 8140211
TI  - Bronchiolitis obliterans--current concepts.
AB  - We review current concepts about the clinical manifestations, diagnosis and
      treatment of patients with bronchiolitis obliterans (BO) with emphasis on
      clinical/pathological correlations and recent developments. BO is a relatively
      rare disease, but its incidence is probably higher than generally believed and is
      continuously rising, partly because of better recognition, but also because of
      increased exposure to industrial fumes, and its occurrence in lung
      transplantation. BO is characterized histologically by varying degrees of
      obliteration of the lumen of the respiratory bronchioles by organizing connective
      tissue often extending into the alveoli ('proliferative' BO with organizing
      pneumonia--BOOP) or by more extensive fibrosis and scarring of the more proximal,
      conductive bronchioles ('constrictive' BO). Diverse clinical conditions have been
      associated with the development of BO, notably viral and mycoplasma infection,
      toxic fume exposure and immune reactions in the setting of a collagen vascular
      disease, drug reaction or organ transplantation. The clinical course and features
      of BO may vary considerably according to the aetiology, histological pattern and
      stage of the disease. The most common presentation is that of a progressive dry
      cough and dyspnea, associated with diffuse patchy interstitial lung infiltrates
      on chest X-ray. In the more advanced cases, lung function tests show either
      restrictive or obstructive defects, depending on the extent of alveolar
      involvement, and hypoxemia without CO2 retention. The diagnosis is often possible
      on clinical grounds, however, in a seriously ill patient uncertainty should be
      resolved by tissue diagnosis, preferably by open lung biopsy. Treatment is based
      on symptomatic therapy. The use of corticosteroids is controversial, but common.
      Patients with BOOP are exceptional, in that there may be no underlying condition
      ('idiopathic' BOOP or cryptogenic organizing pneumonia--COP), a restrictive
      ventilatory defect is usual and the response to corticosteroids often remarkable.

PMID- 8140212
TI  - The role of serotonin 5HT2 receptor antagonism in the control of coronary artery
      disease.

PMID- 8140213
TI  - Malaria prophylaxis: identifying risk groups for non-compliance.
AB  - To investigate behaviour in the use of drug prophylaxis against malaria and the
      risk factors for non-compliance, 507 European or North American travelers
      returning from endemic areas were studied retrospectively at Berlin in a 11-year
      period from 1980 to 1990. Compliance was significantly correlated with shorter
      travel duration: the group with good compliance stayed 37.2 +/- 38.5 days (mean
      +/- SD) in contrast to 69.8 +/- 93.5 days in the group of patients with no
      compliance (p = 0.00001). Older patients were significantly more compliant than
      patients aged < 55 years (20/27 compliant at > 54 years vs. 175/476 at < 55
      years; p = 0.0001). Compliance was significantly affected by travel destination
      (Southern and East African regions; p = 0.0054), age (< or = 15 and > or = 55
      years, respectively; p = 0.0001), and reason of travel (package tours; p =
      0.0001). CART analysis confirmed logistic regression analysis with respect to age
      and travel type, and revealed that patients using only one information source
      were significantly more compliant than those using two or more information
      sources. Travel agencies were nearly as well informed as Institutes of Tropical
      Medicine, but family doctors had a significant incidence of giving wrong advice.
      This study should enable medical personnel dealing with prophylactic advice
      against malaria to identify patients at high risk for non-compliance, and to
      educate them more carefully than other travellers regarding antimalarial drug
      prophylaxis.

PMID- 8140214
TI  - Subacute sclerosing panencephalitis in Wales.
AB  - Twenty cases of subacute sclerosing panencephalitis (SSPE) occurring over an 18
      year period in Wales are described and used as the basis for a comparison of
      measles infection, vaccination rates and the incidence of SSPE in England and
      Wales. Rates of measles infection were higher in Wales in all age groups, and
      fewer Welsh children were vaccinated, which maintained a high risk of SSPE per
      case of measles. Following vaccination, there was a more pronounced change in the
      age distribution of measles infection in Wales than in England, and it is
      proposed that one contribution to the high frequency of SSPE in the 1980s was the
      reservoir of measles in unvaccinated 2-4-year-olds, acting as a source of
      infection for children aged < 2 years, in whom the risk of SSPE following measles
      is known to be higher than in other groups.

PMID- 8140215
TI  - Acute renal failure in earthquake victims in Iran: epidemiology and management.
AB  - The 1990 Iran earthquake affected two provinces with a population of 2.3 million,
      resulting in at least 13,888 deaths and 43,390 injured, and in 33,615
      hospitalizations. Overall mortality among hospitalized patients was 0.17%. Acute
      renal failure (ARF) requiring dialysis support was diagnosed in 156 patients
      nationwide, with a mortality rate of 14%. Three teaching hospitals of the Tehran
      University of Medical Sciences admitted 495 patients, with overall mortality of
      7.5%. Of these, 30 (6%) required dialysis support, with mortality of 40%,
      accounting for one-third of all deaths. On admission, patients with ARF were more
      severely injured, with significantly higher incidence of multiple trauma,
      peripheral nerve damage, elevated plasma concentrations of muscle enzymes,
      potassium and phosphate, and abnormal urinalysis. In one of the three hospitals,
      patients were treated with a standardized hydration protocol coupled with a
      cautious approach to fasciotomy. The incidence of ARF, mortality associated with
      ARF, and fasciotomy were lower in this group. Our limited experience suggests
      that this standardized approach to prevention and treatment of ARF in earthquake
      victims may be helpful.

PMID- 8140216
TI  - Ventricular aneurysmectomy: indications, operative findings and outcome at a
      single centre.
AB  - We assessed all patients (n = 120) who underwent left ventricular aneurysmectomy
      as part of a cardiac surgical procedure at the Groby Road Hospital subregional
      cardiothoracic centre (1980-1990). Of these, 71% had had only one prior
      myocardial infarction and 84% had symptoms generally associated with aneurysms
      (congestive cardiac failure, ventricular arrythmias or systemic embolism). The
      indication for surgery was a combination of angina and aneurysm-related symptoms
      in 43%, one or more aneurysm-related symptoms in 35%, and angina alone in 22%.
      The majority of patients (57%) underwent aneurysmectomy and coronary artery
      bypass grafting, although 35% underwent aneurysmectomy alone. Most (61%)
      aneurysms were > 6 cm in size, and 75% were located at the apex of the left
      ventricle. Forty per cent had a mural thrombus, and there was no relationship
      between prior warfarin use and occurrence of mural thrombus. Overall
      perioperative mortality was 17% (20 patients), although mortality halved between
      the first and second halves of the study period. The main reason for
      perioperative was pump failure. Seventeen patients died late during follow-up
      (mean 52.5 months), the main cause being further myocardial infarction.
      Nevertheless, 65% were still alive at 5 years, and 81% and 66% of survivors were
      still better than pre-operatively at 5 and 8 years, respectively. Post-operative
      improvement was equally as good in patients who underwent aneurysmectomy alone,
      or those operated on for aneurysm-related symptoms, as in the whole group. In
      logistic regression analysis, the only predictor of adverse long-term outcome was
      the number of previous myocardial infarctions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140217
TI  - Bilateral phaeochromocytomas in von Hippel-Lindau disease: diagnosis by adrenal
      vein sampling and catecholamine assay.
AB  - Three unrelated patients with von Hippel-Lindau disease had phaeochromocytomas
      diagnosed as a result of screening in their third decade. All had raised 24-h
      urinary noradrenaline levels and obvious unilateral adrenal tumours on ultrasound
      scanning and computed tomography. The contralateral adrenal appeared either
      normal or equivocally abnormal using the same imaging techniques. Radiolabelled
      meta-iodo-benzylguanidine uptake and enhanced T2-weighted magnetic resonance
      signals confirmed the ipsilateral lesion, but showed no abnormality in the
      contralateral adrenal. Nevertheless, venous sampling demonstrated abnormally
      elevated noradrenaline:adrenaline ratios (normal < 1) in blood draining both
      adrenals in all three patients. All underwent bilateral adrenalectomy:
      histological examination confirmed bilateral phaeochromocytomas in all three
      patients, with the smaller adrenal showing tumours between 3 and 11 mm in
      diameter. A fourth patient with von Hippel-Lindau disease was also evaluated
      because of a left 'suprarenal' mass discovered by ultrasound scanning. Urinary
      and plasma catecholamines were normal. Computed tomography showed a normal right
      adrenal, with a left para-aortic mass lying superior to the left adrenal.
      Magnetic resonance scanning showed an enhanced T2 signal from the mass, which
      also showed positive uptake with radiolabelled mIBG. At operation, a non
      secretory left para-aortic paraganglioma was found. Venous sampling suggested
      that the left adrenal was normal, and this was confirmed on histology. Venous
      sampling for catecholamine assays is effective in locating small bilateral
      phaeochromocytomas and defining a normal adrenal gland, and can be useful in
      preventing unnecessary or repeat operations in patients with non Hippel-Lindau
      disease.

PMID- 8140218
TI  - Dilatation of the colon complicating acute self-limited colitis.
AB  - Colonic dilatation has been reported as an occasional complication of infectious
      colitis in single case reports and short series, but no large series has been
      published. We analysed 19 cases of self-limited colitis complicated by colonic
      dilatation, with infective agents identified in 14, admitted to a Regional
      Infectious Diseases Unit. Colonic dilatation, defined as a minimum transverse
      colonic diameter of 7 cm on plain abdominal X-ray, was associated with
      approximately 1% of cases of notifiable diarrhoea requiring hospital admission.
      The clinical course was associated with pyrexia (in 90%), tachycardia (in 90%),
      hypoalbuminaemia (in 100%), anaemia (in 84%) and reactive thrombocytosis (in
      63%). There was a history of antidiarrhoeal agents or opiate analgesia in
      eighteen patients (95%). Intensive medical management, consisting of intravenous
      antibiotics, steroids, supplementary nutrition and withdrawal of anti-motility
      agents, resulted in resolution in 17 patients. Two patients required subtotal
      colectomy for perforation of the transverse colon, but neither developed severe
      peritonitis, and both subsequently underwent reversal of ileostomy. With early
      recognition and close observation of colonic dilatation in patients with acute
      diarrhoea, most cases can be successfully managed conservatively with
      preservation of the colon. Surgical intervention should be considered in patients
      with progressive colonic dilatation despite intensive medical management. There
      were no clinically useful parameters distinguishing self-limited colitis from
      inflammatory bowel disease acutely, so initial management should cover both
      possibilities.

PMID- 8140219
TI  - Hyperventilation and chronic fatigue syndrome.
AB  - We studied the link between chronic fatigue syndrome (CFS) and hyperventilation
      in 31 consecutive attenders at a chronic fatigue clinic (19 females, 12 males)
      who fulfilled criteria for CFS based on both Oxford and Joint CDC/NIH criteria.
      All experienced profound fatigue and fatigability associated with minimal
      exertion, in 66% developing after an infective episode. Alternative causes of
      fatigue were excluded. Hyperventilation was studied during a 43-min protocol in
      which end-tidal PCO2 (PETCO2) was measured non-invasively by capnograph or mass
      spectrometer via a fine catheter taped in a nostril at rest, during and after
      exercise (10-50 W) and for 10 min during recovery from voluntary overbreathing to
      approximately 2.7 kPa (20 mmHg). PETCO2 < 4 kPa (30 mmHg) at rest, during or
      after exercise, or at 5 min after the end of voluntary overbreathing, suggested
      either hyperventilation or a tendency to hyperventilate. Most patients were able
      voluntarily to overbreathe, but not all were able to exercise. Twenty-two
      patients (71%) had no evidence of hyperventilation during any aspect of the test.
      Only four patients had unequivocal hyperventilation, in one associated with
      asthma and in three with panic. Only one patient with severe functional
      disability and agoraphobia had hyperventilation with no other obvious cause. A
      further five patients had borderline hyperventilation, in which PETCO2 was < 4
      kPa (30 mmHg) for no more than 2 min, when we would have expected it to be
      normal. There was no association between level of functional impairment and
      degree of hyperventilation. There is only a weak association between
      hyperventilation and chronic fatigue syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140220
TI  - Chest pain with normal coronary arteries.

PMID- 8140221
TI  - Chest pain with normal coronary arteries.

PMID- 8140222
TI  - Chest pain with normal coronary arteries.

PMID- 8140223
TI  - Diabetes screening.

PMID- 8140224
TI  - Imaging aspects of new techniques in orthopedic surgery.
AB  - Advances and new techniques in orthopedic surgery continue to challenge the
      radiologist in our attempts to maintain familiarity with imaging aspects of these
      procedures. This article is an attempt to review several of these new orthopedic
      techniques and modifications of standard procedures. In addition the use of
      computed radiography, a recently developed modification of digital technology, in
      musculoskeletal imaging was also assessed. It is our responsibility to recognize
      the normal radiologic appearance of these new techniques. Perhaps more
      importantly better understanding of these new orthopedic surgical procedures may
      allow detection of complications at the earliest stage, improving patient
      management and clinical outcome.

PMID- 8140225
TI  - Nuclear medicine approaches to musculoskeletal disease. Current status.
AB  - With the advent of bone scintigraphy, physicians achieved earlier detection of
      metastatic disease. In the prior two decades, bone imaging has expanded into the
      realm of tomography (SPECT, PET), and diverse clinical applications, including
      trauma, grafts, benign disease, and tumor imaging.

PMID- 8140226
TI  - Computed tomographic imaging of the musculoskeletal system. Current status.
AB  - Computed tomography has emerged as the "workhorse" of specialized musculoskeletal
      imaging. It provides rapid, detailed, clinically relevant studies of bones,
      joints, and associated soft tissues. Applications in trauma, inflammatory
      disease, neoplasia, pediatric orthopedics, and joint reconstruction are
      discussed. Advances in prosthetic design, radiation oncology applications, and
      data acquisition techniques will also be addressed.

PMID- 8140228
TI  - Recent advances in magnetic resonance imaging of the musculoskeletal system.
AB  - Numerous recent technical innovations in magnetic resonance imaging have
      dramatically improved the imaging evaluation of musculoskeletal disease; however,
      with the introduction of new techniques comes the risk of inappropriate
      applications and unanticipated pitfalls in interpretation. Some of the practical
      and theoretical implications of these recent innovations as well as potential
      caveats associated with their use are highlighted in the following discussion.

PMID- 8140227
TI  - Ultrasonography of the musculoskeletal system.
AB  - This article reviews the numerous applications of ultrasound in the
      musculoskeletal system. Emphasis is made on the important and often under
      utilized role of ultrasound in infections, vascular lesions, arthritis, and
      trauma.

PMID- 8140229
TI  - Magnetic resonance spectroscopy studies of human muscle.
AB  - The use of MRS has become more widespread as cost and availability have improved.
      It has been demonstrated that MRS of human skeletal muscle can play a significant
      role in (1) understanding healthy muscle metabolism and the mechanisms of muscle
      fatigue, (2) understanding the effects of disease on muscle metabolism and
      function, (3) monitoring the efficacy of therapeutic intervention, and (4) the
      confirmation of disease diagnoses. The results of the 31P MRS studies of disease
      are summarized in the Table 1. A few conditions (McArdle's, PFK deficiency) are
      associated with failure to develop acidosis during exercise. This response
      appears to be relatively specific to these metabolic myopathies. For most of the
      conditions reviewed here, however, the metabolic findings of reduced PCr/Pi and
      greater acidosis during exercise with impaired recovery of PCr/Pi and pH are very
      similar. The nonspecificity of the MRS results suggests the possibility that a
      common mechanism may be at work in all of these diseases. A major question to
      arise from clinical studies using MRS concerns the extent to which deconditioning
      may have played a role in some of these findings. This is because conditions
      associated with muscle weakness, rapid fatiguability, and muscle pain during or
      following vigorous physical activity may also be those that lead to
      deconditioning. In virtually all studies reviewed here, healthy, active subjects
      were used as controls. There are no examples in which controls were appropriately
      matched to the subjects for their level of conditioning. Conditioning could be
      assessed by questionnaire, activity logs, activity monitoring devices, or
      measurements of conditioning effects such as maximal oxygen consumption. The role
      of deconditioning in the decreased quality of life of persons with chronic
      diseases has not been fully explored. Future studies of chronic disease using MRS
      should combine MRS with other techniques to further probe the mechanisms of
      muscle metabolism under various conditions, and the extent to which these
      mechanisms are sensitive to the level of physical conditioning.

PMID- 8140230
TI  - Contrast enhancement in musculoskeletal imaging. Current status.
AB  - This article discusses intravenous and intra-articular uses of contrast in cross
      sectional imaging for the evaluation of musculoskeletal abnormalities. Emphasis
      will be placed upon the important traditional uses of contrast-enhanced computed
      tomography and the recent developments in contrast-enhanced magnetic resonance
      imaging.

PMID- 8140231
TI  - Recent advances in pediatric musculoskeletal imaging.
AB  - The current role of ultrasound, computed tomography, magnetic resonance imaging,
      and scintigraphy in the evaluation of pediatric musculoskeletal disorders is
      reviewed. Magnetic resonance imaging and ultrasound, which do not utilize
      ionizing radiation and, as far as is known, appear to have no deleterious
      biologic effects, are particularly valuable modalities in the pediatric
      population.

PMID- 8140232
TI  - Current status of musculoskeletal interventional radiology.
AB  - This article details many of the latest developments in the field of
      musculoskeletal interventional radiology. Some of the topics included in this
      discussion are percutaneous biopsy of musculoskeletal lesions, automated
      percutaneous discectomy, facet joint arthrography, percutaneous vertebroplasty,
      and percutaneous drainage of abscesses.

PMID- 8140233
TI  - Musculoskeletal manifestations of human immunodeficiency virus infection: review
      of imaging characteristics.
AB  - As the AIDS epidemic progresses, more and more cases of musculoskeletal
      involvement have been seen and reported. Although HIV infection does not
      typically involve the musculoskeletal system, a number of abnormalities have been
      detected. The radiographic manifestations of AIDS in the musculoskeletal system
      are discussed in this article.

PMID- 8140234
TI  - [Determination of the growth rate of tumor-like space-occupying lesions of the
      bones. A study of 1154 lesions of the long tubular bones].
AB  - In 1088 primary and secondary bone tumors and tumorlike lesions and in 66
      inflammatory lesions, the growth rate was graded according to the Lodwick
      classification. Grade IA and grade IB were correlated with benign lesions in
      99.8% and 91.3% of cases, respectively. In contrast, grade III and grade II were
      associated with malignant tumors in 100% and 89.6%, respectively. With increasing
      age, the proportion of malignant tumors among those graded as IB or II increased
      significantly. Tumors classed as grade IC were benign in 57.5% and malignant in
      42.5% of cases. The growth rates of the individual tumor entities were analyzed.

PMID- 8140235
TI  - [The recognition of osteofibrous dysplasia Campanacci. Morphology, radiology,
      clinical picture and therapy].
AB  - Radiologically osteofibrous dysplasia of the tibia is characterized by an
      eccentrically localized osteolytic lesion in the diaphysis with the appearance of
      ground glass. However, this is a very rare lesion, making a correct diagnosis
      difficult, especially since fibrous dysplasia and adamantinoma of the tibia have
      to be taken into account in the differential diagnosis of the disease. A
      definitive diagnosis can only be made histologically. The rather aggressive
      growth pattern of osteofibrous dysplasia as compared to fibrous dysplasia that
      has been reported in literature should not be generalized and it must be taken
      into consideration that surgery may be performed too early during the growth
      phase.

PMID- 8140236
TI  - [The multilocular occlusive form of fibromuscular hyperplasia].
AB  - The rare case of a 19-year-old man with fibromuscular hyperplasia (FMH) affecting
      several arteries with tubular stenosis and occlusions is presented. Involved were
      both internal carotid arteries, the right renal artery, celiac axis and the
      superior mesenteric artery. The disease pattern of FMH is discussed regarding
      frequency, vascular morphology and differential diagnosis.

PMID- 8140237
TI  - [Reconstruction possibilities following resection of malignant musculoskeletal
      tumors].
AB  - Great advances have been achieved in the treatment of musculoskeletal tumors, and
      as a result limb-conserving resection is now possible in most cases. These
      advances are based on adjuvant therapy, development of histological criteria, new
      surgical techniques, and improved imaging methods. The use of computed tomography
      and magnetic resonance imaging has allowed more accurate preoperative staging. At
      the same time, an improvement in prognosis has also been achieved. After
      resection of the tumor, the following methods of reconstruction are available:
      reconstruction with no implant, endoprosthetic replacement, autogenous grafting,
      and allograft replacement. Postoperative monitoring is performed with plain-film
      radiography.

PMID- 8140238
TI  - [Parapneumonic ARDS. The radiomorphologic transition of a pneumonia into an
      ARDS].
AB  - Serial chest X-rays of 14 patients with parapneumonic ARDS (PARDS) were analysed
      retrospectively. Typical findings on chest X-ray films occurred after a latency
      period of 12-24 h following the clinical start of PARDS. We found some "early
      signs" of PARDS, such as central interstitial paravascular edema (14/14),
      bilateral hilar infiltrates (9/14) and the absence of pleural effusion (12/14).

PMID- 8140239
TI  - [Computed tomography of the paranasal sinus prior to endonasal surgery].
AB  - In a retrospective study 170 computed tomographies recorded in patients with
      chronic sinus disease were evaluated. The extent of sinus disease and the
      involvement of the different paranasal sinuses were well seen. Up to now 50
      patients have undergone surgical treatment. The coincidence of the preoperative
      CT with the intraoperative findings was about 90%. Anatomic particularities of
      the paranasal sinus in an individual patient may predispose to recurrent
      sinusitis or mean there is an increased risk of intraoperative complications. The
      main risk factors are a far lateral location of the posterior ethmoid cells
      (28.8%), a much lower position of the cribriform plate in comparison to the
      ethmoid roof (11.8%), and extensive lateral aeration of the sphenoidal sinus
      (1.2%). All patients should undergo CT scanning in coronal and axial planes prior
      to endonasal sinus surgery. This gives a guide for detection of inflammatory
      lesions and anatomic variations or anomalies, thus making it possible to prevent
      intraoperative complications.

PMID- 8140240
TI  - [Ct-portography in diffuse liver steatosis. Potential for a false-negative
      assessment].
AB  - CT portography is the most sensitive technique currently available for the
      preoperative diagnosis of liver metastases. We report on a patient with liver
      steatosis in whom ultrasound examination revealed two liver metastases in the
      follow up after resection of a papillary carcinoma. The liver metastases could be
      clearly identified both on plain CT and on enhanced CT with dynamic bolus
      contrast medium injection. Because of the small difference in attenuation values
      between liver parenchyma and metastases the two liver metastases had not been
      recognized on CT portography. When severe and diffuse liver steatosis is present
      CT portography may fail to detect metastases or small hepatocellular carcinoma.

PMID- 8140241
TI  - [Cytomegalovirus infection of the intestinal tract. Computed tomographic findings
      in AIDS patients].
AB  - To check the value of computed tomography (CT) in the diagnosis of
      cytomegalovirus (CMV) infection of the intestine, CT findings in ten patients
      with coloscopically proven CMV infection were reviewed. All patients were
      chronically ill men with AIDS. In nine of the ten cases CT scans of the small
      intestine and/or colon disclosed abnormalities. The predominant alteration (9/9)
      was a symmetric wall thickening in the bowel segments involved (10-30 mm). The
      location and extent showed good agreement with the inflammatory areas seen on
      coloscopy. The cecum and terminal ileum were the regions most frequently
      affected. In seven of the nine patients with CT abnormalities CT revealed
      pericolonic inflammation, particularly around the cecum. Lymph nodes were
      increased but not enlarged. Comparison of the findings in intestinal CMV
      infection with those in other AIDS-related diseases suggests that CT may be to
      limit the differential diagnosis. Abdominal CT serves as suitable primary imaging
      modality for the initial evaluation of patients with AIDS and abdominal symptoms
      of unknown etiology.

PMID- 8140242
TI  - [An unclear lower abdominal pain].

PMID- 8140243
TI  - [Multiple bony lesions with abdominal calcifications].

PMID- 8140244
TI  - [In vitro antibacterial activity of isoxazolyl++ naphthoquinones. I].
AB  - The in vitro antibacterial activity of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)
      1,4 naphthoquinone-4-imine (I) and three of this derivatives against
      Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus
      mirabilis y Morganella morganii was investigated. From the four naphthoquinone
      imine studied, compound I exhibited activity against S. aureus. This effect was
      observed even in oxygen atmosphere with 5% CO2 and in the presence of human
      albumin. The development of drug-resistant strains by serial passage in media
      with concentrations lower than the C.I.M. was determined in 31 strains of S.
      aureus from clinical material and one from collection. No significant differences
      in C.I.M. were observed.

PMID- 8140245
TI  - [Incidence of various etiologic agents of superficial mycosis].
AB  - In a retrospective review of laboratory records at the Department of Mycology,
      National Institute of Microbiology "Dr. Carlos G. Malbran", during the period
      June 1989-July 1991, 1225 putatively immunocompetent cases of superficial mycoses
      were identified. Ninety five percent of these patients were adults and 5%
      children. Among the total cases, dermatomycoses were caused, 67.6% by
      dermatophytes, 25.9% by yeasts, 5.9% by Malassezia furfur. and 0.5% by other
      fungi, as proven by the isolation of the etiological agents. (Figure 1, Table 2).
      Among the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes
      greatly predominated accounting for 66.6% and 20.0% of the isolates,
      respectively, whereas Microsporum canis (8.0%). Epidermophyton floccosum (5.1%)
      and Microsporum gypseum (0.3%) were found with less frequency (Figure 2). Nails
      (47%) were the most common source of isolates in adults, followed by feet (28%),
      smooth skin (15%), groin (5%) and hands (2%) (Table 1). Regarding the relative
      efficiency of the diagnostic methods, the analyses of laboratory results
      evidenced that, 98% of the cases with clinical findings compatible with mycoses
      and 76% of the cases with positive cultures (Table 1) were identified by
      microscopic observation.

PMID- 8140246
TI  - [Multiple resistance to heavy metals and antibiotics in bacteria isolated from
      the Riachuelo].
AB  - Riachuelo is a heavy contaminated course of water, partially surrounding Buenos
      Aires city. The presence of bacteria resistant to antibiotics and heavy metals
      was studied. Among the isolated Gram positive colonies, 65, 59 and 48% were
      resistant to 60 micrograms/ml of Pb++, Zn++ and Cd++, respectively, and 20% grew
      in the presence of 50 micrograms/6ml gentamicin. Most of these microorganisms
      belonged to the order Actinomycetales. Accordingly, high percentages of
      resistance were detected (among the 11 Gram negative isolates (Enterobacteriaceae
      and Pseudomonaceae), although only one isolate was gentamicin resistant. Four
      Gram negative isolates also showed a broad spectrum of resistance to
      tetracycline, erythromyci, ampicillin, amikacin, chloramphenicol and gentamicin.

PMID- 8140247
TI  - [Isolation of V. cholerae no-01 and V. metschnikovii from sewage of the city of
      Mar del Plata].
AB  - A total of 42 vibrio strains isolated from sewage, together with 7 culture
      collection strains were studied by numerical taxonomy. A simplified clustering is
      shown in Fig. 1. Two important phena were determined. Phenon 1, identified as V.
      cholerae non-01, formed at 0.90% S, contains 32 sewage strains and 2 reference
      strains. Phenon 2, identified as V. metschnikovii, formed at 0.85% S, contains 5
      sewage strains. No typical marine vibrio species were isolated. The phenotypic
      characteristics of 2 phena are shown in Table 2. All V. cholerae non-01 were
      haemolytic, proteolytic and lipolytic. They also showed some phenotypic
      characteristics (degradation of esculin, 81.2%; utilization of: D-glucuronate,
      88.2%; cellobiose, 47.0% and lactose, 47.0%), and growth in NaCl 6%, 91.1%.
      According to literature references, the survival of V. cholerae non-01 in Mar del
      Plata marine environment is possible.

PMID- 8140248
TI  - [Biodeterioration of materials: microbiological corrosion and biofouling].

PMID- 8140249
TI  - Technologic considerations and practical limitations in the use of quantitative
      angiography during percutaneous coronary recanalization.

PMID- 8140250
TI  - Quantitative coronary angiography (QCA) in interventional cardiology: clinical
      application of QCA measurements.

PMID- 8140251
TI  - Medium- and long-term outcome after coronary balloon angioplasty.

PMID- 8140252
TI  - Dietary lipids and immune function.
AB  - Interest in the use of alternative dietary lipids to prevent or control human
      disease has gained scientific support from numerous studies which have uncovered
      beneficial effects of increased amounts of polyunsaturated fish and plant oils
      upon such diverse disease processes as atherosclerosis and coronary heart
      disease, rheumatoid arthritis, post-operative and post-traumatic recovery, and
      sepsis. The immunologic processes which underly these pathologic states, and the
      possible ways in which dietary lipids may influence immunologic function are
      areas of active research. This review aims to summarize the current views of
      understanding how immune-mediated processes and inflammatory states may be
      altered by the content and types of lipids in the diet.

PMID- 8140253
TI  - The role of boron in nutrition and metabolism.
AB  - A large number of responses to dietary boron occur when the boron content of the
      diet is manipulated. Numerous studies suggest that boron interacts with other
      nutrients and plays a regulatory role in the metabolism of minerals, such as
      calcium, and subsequently bone metabolism. Although the mechanism of action has
      not been defined, it may be mediated by increasing the concentration of steroid
      hormones such as testosterone and beta-oestradiol. Boron is obtained from a diet
      rich in fruits, vegetables, nuts and legumes. The daily intake has been estimated
      to range from 0.3-41 mg per day. The wide range is due to the variation of the
      analytical methods used and differences in the soil content of boron. Based on a
      limited number of studies, increasing dietary boron results in increases in the
      boron concentration of all tissues. Large amounts of boron are well tolerated
      while consistent signs of deficiency include depressed growth and a reduction in
      some blood indices, particularly steroid hormone concentrations. Via its effect
      on steroid hormones and interaction with mineral metabolism, boron may be
      involved in a number of clinical conditions such as arthritis. Further research
      is required before boron is accepted as an essential nutrient for humans.

PMID- 8140254
TI  - Is vitamin E supplementation a useful agent in AIDS therapy?
AB  - Acquired immune deficiency syndrome (AIDS) is a clinical disorder caused by a
      retrovirus infection, representing the end point in a progressive sequence of
      immunosuppressive changes. The literature is briefly summarized as to
      immunological, nutritional and other pathological modifications caused by AIDS,
      and properties of immunoenhancing, anti-oxidant and undernutrition-restoration of
      vitamin E supplementation. All these abnormalities in AIDS are similar to those
      that are stimulated or restored by intake of high doses of vitamin E. The
      drawbacks of pharmacological therapy like zidovudine (AZT), e.g. deleterious
      toxic side effects, inability to improve the immune dysfunctions and
      undernutrition initiated by the retrovirus infection, and finding of AZT
      resistant HIV strains, necessitate new strategies for the clinical trials of
      novel therapies to treat AIDS with the existing medical therapies. Low toxicity
      nutritional agents with immunoenhancing and antioxidant activities like vitamin E
      may help to normalize retrovirus-induced immune dysfunctions, undernutrition and
      other pathological symptoms, thereby retarding the progression of the disease to
      AIDS. To address this vitamin E therapeutic role in HIV-positive individuals,
      This paper presents a review of vitamin E-related therapeutic roles in animals
      and humans, thereby showing why vitamin E supplementation could be used as a
      useful therapeutic agent in human AIDS therapy. Since there is a paucity of
      information available regarding the nutritional therapy in AIDS individuals, our
      purpose is to provide evidence from animal models or humans of the potential
      therapeutic role of vitamin E supplementation in the treatment of AIDS
      individuals.

PMID- 8140256
TI  - The grasshopper, Drosophila and neuronal homology (advantages of the insect
      nervous system for the neuroscientist).

PMID- 8140255
TI  - Vitamin D deficiency: a culprit in metabolic bone disease.
AB  - Bone formation and bone remodeling are complicated processes regulated by
      systemic hormones and paracrine factors which regulate calcium and phosphate
      fluxes and cellular differentiation. The many actions of vitamin D reinforces its
      importance in the process of growth, maturation and aging of bone. An
      understanding of these important regulators of bone metabolism is important to
      understanding the clinical disorders as they are related to alterations in
      vitamin D metabolism and metabolic bone disease. Specific disorders of vitamin D
      metabolism can be related to clinical disease states of aging, altered
      lifestyles, gastrointestinal, renal and hepatic disease. A classification of
      altered vitamin D metabolism as related to its clinical states is presented. The
      scope of vitamin D deficiency from childhood rickets to adult osteomalacia and
      osteoporosis is presented, Intermediate syndromes of high turnover osteoporosis,
      subclinical vitamin D-deficiency states, role of vitamin D analogues in treating
      type I and type II osteoporosis is discussed. Treatment guidelines for managing
      this scope of clinical vitamin D disorders are provided.

PMID- 8140257
TI  - The neurotrophic activity of fibroblast growth factors.

PMID- 8140258
TI  - Thixotropy in skeletal muscle and in muscle spindles: a review.

PMID- 8140260
TI  - Effects of prostaglandins and indomethacin on gastric emptying in the rat.
AB  - Prostaglandins have been shown to stimulate contraction of gastrointestinal
      smooth muscle in vitro, and their synthesis has been reported in different
      gastrointestinal diseases. The aim of this study was to determine the different
      effects of PGs and indomethacin on gastric emptying in the rat in vivo, and to
      investigate their possible role as modulators of osmolarity induced changes in
      gastric emptying. Rats were fed via gastric tube with suspensions of various
      osmolarity containing different prostaglandins or indomethacin. Gastric emptying,
      measured by the quantity of food remaining in the stomach, was studied by a
      noninvasive technique using orally administered nonabsorbable marker 141Cerium.
      PGE2 given orally and its synthetic analogue 16-16-dimethyl PGE2 given
      subcutaneously caused significant delay of gastric emptying, while PGF2 alpha
      increased gastric emptying regardless of the administration route. Tube-feeding
      with high osmolarity suspension significantly reduced emptying rate of 141Cerium
      compared to feeding with low osmolarity suspension. Gastric emptying rate of the
      tracer was significantly higher in rats fed with low osmolarity test meal, in
      comparison to those fed with high osmolarity test meal. This effect was
      completely antagonized by indomethacin. Due to the known inhibitory effect of
      indomethacin on cyclooxygenase, the effects observed in the present study are
      also presumably mediated by the action of prostaglandins.

PMID- 8140259
TI  - The pharmacologic effects of 5-[3,5-bis(1,1-dimethylethyl)-4- hydroxyphenyl]
      1,3,4-thiadiazole-2(3H)-thione, choline salt (CI-986), a novel inhibitor of
      arachidonic acid metabolism in models of inflammation, analgesia and gastric
      irritation.
AB  - CI-986 is a potent inhibitor of 5-lipoxygenase and cyclooxygenase pathway product
      biosynthesis from rat basophilic leukemia (RBL) cells. Because metabolites from
      these pathways have proinflammatory properties, CI-986 was evaluated in several
      acute and chronic models of inflammation and hyperalgesia. The compound inhibited
      swelling in the carrageenan footpad edema, Mycobacterium foot-pad edema and
      adjuvant arthritis models of inflammation with ID40 values of 1.0, 7.7., and 7.2
      mg/kg, respectively. It was roughly equivalent in potency to the standard
      selective cyclooxygenase inhibitor, naproxen (ID40 = 0.7, 6.3, and 3.8 mg/kg,
      respectively). CI-986 was also evaluated in the acetic acid induced writhing
      hyperalgesia assay (ID50 = 0.23 mg/kg) and was approximately equipotent with
      indomethacin (ID50 = 0.87 mg/kg). Although the effects of CI-986 were similar to
      those of standard nonsteroidal antiinflammatory drugs (NSAIDs) in the
      inflammation models, its gastrointestinal profile was unique. CI-986 caused no
      gastrointestinal irritation at doses up to 200 mg/kg in acute and chronic
      studies. In contrast, standard NSAIDs caused ulcers at doses of 3.7-37 mg/kg
      after a single dose. Moreover, CI-986 inhibited the release of LTC4 and PGE2 by
      gastric mucosa and reduced mucosal and vascular damage induced by oral
      administration of absolute ethanol to rats. These results indicate that CI-986 is
      a potent nonulcerogenic antiinflammatory agent with novel pharmacologic
      properties.

PMID- 8140261
TI  - Increased PGE2 from human monocytes isolated in the luteal phase of the menstrual
      cycle. Implications for immunity?
AB  - The reproductive hormones are implicated in the well documented sexual dimorphism
      in cellular and immune responses. Prostaglandins (PGs) are mediators of the
      immune response with their concentration and relative amounts being pivotal to
      their impact. In resident peritoneal macrophages isolated from mice we had
      previously noted that the cells from females synthesized significantly more PG
      than males. In these experiments we investigated whether PG metabolism in the
      human monocyte was influenced by gender and by stage of the menstrual cycle.
      Monocytes isolated from the female and activated in vitro with LPS produced on
      average significantly more PG into the medium than the males. Among females,
      significantly more PG was found in the medium from cells isolated during the
      luteal phase of the cycle than during the early follicular phase. It was also in
      this luteal phase in which the female differed substantially from males. We
      suggest that the in vivo hormonal changes associated with the menstrual cycle
      modulate monocyte synthesis of PG and other immune modulators such as IL-1. This
      could be a key to understanding differences in vulnerability between males and
      females as well as within phases of the cycle, to immune and inflammatory insult.

PMID- 8140262
TI  - NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H
      synthase/cyclooxygenase (COX-2) activity in vitro.
AB  - NS-398 is a novel anti-inflammatory and analgesic agent which produces much fewer
      gastrointestinal lesions in rats. Recently, two forms of cyclooxygenase have been
      identified: a COX-1 first purified from ram seminal vesicles and a newly
      discovered mitogen-inducible form (COX-2). Effects of NS-398 on activities of
      these two distinct forms of COX were investigated. COX-1 purified from ram
      seminal vesicles and COX-2 isolated from sheep placenta (purity was 70%) were
      used. The COX-1 activity was completely unaffected by 10(-4) M NS-398, whereas
      the COX-2 activity was concentration-dependently inhibited, the IC50 value being
      3.8 x 10(-6) M. Indomethacin inhibited both COX-1 and COX-2 activity to the same
      degree, the IC50 values being 7.4 x 10(-7) M and 9.7 x 10(-7) M, respectively.
      The anti-inflammatory and analgesic effects of NS-398 were almost as potent as
      indomethacin, the effective dose range being 0.3 approximately 5 mg/kg in rats.
      The gastrointestinal lesions related to NS-398 were not significant following a
      dose of 1000 mg/kg given orally. NS-398 is the first documented agent to have
      selective inhibition for COX-2, which may result in the less gastrointestinal
      toxicity.

PMID- 8140263
TI  - Luteal maintenance during early pregnancy in the pig: role for prostaglandin E2.
AB  - We previously demonstrated that prostaglandin E2 (PGE) directly inhibits
      prostaglandin F2 alpha (PGF)-induced regression of individual pig corpora lutea
      (CL) in a dose dependent manner. The present experiments were conducted to 1)
      characterize and compare uterine secretion of PGE and PGF during the estrous
      cycle and early pregnancy and 2) evaluate the local effect of the conceptus on
      uterine prostaglandin secretion and associated CL function in unilaterally
      pregnant pigs. In Experiment 1, utero-ovarian venous blood samples were collected
      from two nonpregnant and two pregnant gilts at 3-h intervals from day 10 through
      16 (first day of estrus or mating = day 0) for quantitation of uterine PGE and
      PGF secretion. In Experiment 2, gilts (n = 4) were made unilaterally pregnant on
      day 2, and utero-ovarian venous catheters were placed bilaterally to determine if
      differences in PGE and/or PGF secretion might account for the known
      luteotrophic/antiluteolytic effect of the gravid uterine horn on the CL of the
      ipsilateral ovary. During the estrous cycle (Experiment 1), pulsatile secretion
      of PGF increased markedly on day 13 and continued to increase through day 16. PGE
      secretion also increased from day 13 to 16 of the estrous cycle; however,
      concentrations of PGE remained at least 3-fold lower than those of PGF. In
      contrast to changes in non-mated gilts, prostaglandin secretion in mated gilts
      peaked earlier (day 11-12), with PGE predominating. Thereafter, both PGE and PGF
      secretion declined to basal levels where they remained through day 16 of
      pregnancy. During unilateral pregnancy (Experiment 2), PGF concentration in
      nongravid and gravid horns was similar (P > 0.8). In contrast, PGE concentrations
      were greater (P < 0.06) in utero-ovarian venous blood draining the gravid uterine
      horn. This increase in PGE was associated with enhanced CL function on the
      ipsilateral ovary as evidenced by an elevated progesterone content and
      concentration as well as increased CL weights. These data are consistent with a
      role for conceptus-associated increases in uterine PGE secretion in the local
      stimulation of luteal function during early pregnancy in the pig.

PMID- 8140264
TI  - A mid-luteal phase comparison of peritoneal fluid volume and its content of PGF2
      alpha and PGE2 in women with minimal stage endometriosis and a normal pelvis.
AB  - The study was carried out following the approval of our Hospital Ethics Committee
      and an informed patient consent. Samples of peritoneal fluid were collected from
      the Pouch of Douglas at laparoscopy from 32 subjects with minimal stage
      endometriosis (MSE) and 16 without any visible signs of endometriosis (normal
      group). All the subjects were in 20 to 23 day period of their menstrual cycle
      which was histologically confirmed. The endometriosis score was estimated
      according to the American Fertility Score, 1985 and the fluid samples were
      collected in tubes containing heparin/indomethacin and standing in ice. The
      samples were estimated for volume, erythrocyte count, prostaglandin(PG) F2 alpha,
      and PGE2. Radioimmunoassay techniques were used for the estimation of PGs.
      Prostaglandin F2 alpha, was measured in its parent form while PGE2 was converted
      into bicyclic-PGE2 before estimation. The results indicate that the peritoneal
      fluid in women with MSE has higher than normal levels of PGF2 alpha and lower
      than normal levels of PGE2 and its PGE2: PGF2 alpha ratio is also below normal.
      There is no difference in the volume of peritoneal fluid in the two groups.
      Provided the fluid sample is not contaminated with abdominal blood its
      erythrocyte count is not related to its prostaglandin content.

PMID- 8140265
TI  - Management restructuring damages nurses' morale.

PMID- 8140266
TI  - The law and the nurse.

PMID- 8140267
TI  - Domestic violence protocols in Queensland health.

PMID- 8140268
TI  - Bill's story. Taking that one extra step--the role of the advocate.

PMID- 8140269
TI  - The Braithwaite, Macri and Gregory reports.

PMID- 8140270
TI  - New directions in aged care.

PMID- 8140271
TI  - VIP-antiserum inhibits fluid secretion by the inflamed gallbladder mucosa.
AB  - The inflammatory fluid secretion by the gallbladder mucosa in experimental
      cholecystitis is induced by an increased prostaglandin formation and is mediated
      by intramural nerves. In the present study the effect of VIP-antiserum on the
      inflammatory fluid secretion in the gallbladder was tested in a validated
      experimental model in cats. The animals were studied in acute experiments 6 weeks
      after a procedure when the cystic duct was tied and gallstones were implanted in
      the gallbladder. During basal conditions there was a continuous secretion of
      fluid into the lumen of the inflamed gallbladder averaging 0.43 +/- 0.18 ml/h.
      Injection of VIP antiserum, obtained from immunized rabbits and diluted with
      saline 1:10 in a bolus of 4 ml into the coeliac artery reversed this secretion
      into an absorption of 1.72 +/- 0.44 ml h-1 (P < 0.001). VIP-antiserum did not
      affect the fluid adsorption in control animals with an intact gallbladder and
      injection of control serum from rabbits not immunized to VIP did not affect fluid
      secretion in the inflamed gallbladders. The results support the idea that the
      inflammatory fluid secretion in the gallbladder mucosa is mediated by VIP-ergic
      nerve fibres.

PMID- 8140272
TI  - Chemoattractant capacity of bombesin, gastrin-releasing peptide and neuromedin C
      is mediated through PKC activation in murine peritoneal leukocytes.
AB  - Bombesin-like peptides have been recently shown to regulate immune functions. In
      the present work, we have studied their action as chemoattractants for murine
      peritoneal macrophages and lymphocytes. The results showed a significant increase
      in the number of cells that migrate when they are exposed to a gradient of
      bombesin, gastrin-releasing peptide (GRP) or neuromedin C (from 10(-8) to 10(-12)
      M). The most effective of the three neuropeptides studied was GRP, even more than
      formyl-Met-Leu-Phe peptide (FMLP), an established leukocyte chemoattractant. GRP
      action was mediated through specific cell receptors as it was significantly
      reduced in presence of a competitive and specific bombesin receptor antagonist.
      In the presence of retinal, a protein kinase C (PKC) inhibitor, the
      chemoattractant capacity of GRP was considerably reduced. In order to investigate
      further the mechanism of action involved in the GRP effect, we measured PKC
      activity. Peritoneal cells incubated with GRP experimented an increase in PKC
      activity to the same extent of that produced by the PKC activator phorbol
      myristate acetate (PMA). These data prove that bombesin-like peptides are potent
      chemoattractants for murine peritoneal macrophages and lymphocytes, and that
      their action is at least in part mediated through PKC activation.

PMID- 8140273
TI  - Isolation and sequence determination of two N-terminal fragments of islet amyloid
      polypeptide in rat pancreas.
AB  - Using a highly sensitive and specific radioimmunoassay (RIA) for the N-terminal
      hexadecapeptide of islet amyloid polypeptide (IAPP), we isolated two N-terminal
      fragments of IAPP from rat pancreas. They were identified as IAPP(1-16) and
      IAPP(1-17) by amino acid sequencing. The two fragments were also found in rat
      plasma. IAPP(1-37) was the major molecular form of rat IAPP, IAPP(1-16) and
      IAPP(1-17) accounting for 6.0% and 32.3% of the immunoreactivity for the N
      terminal region of the peptide in pancreata of normally fed rats. In human
      pancreas, the N-terminal fragments of IAPP were not present, indicating that the
      processing of IAPP in the pancreas differs between human and rat. Food
      deprivation increased the molar ratios of IAPP(1-16) and IAPP(1-17) to IAPP(1-37)
      in comparison to values for fed rats. Identification of novel fragments of IAPP,
      in addition to IAPP(1-37), offers a promise for the elucidation of the
      physiological function of IAPP and the identification of factors that regulate
      the biosynthesis and catabolism of the peptide.

PMID- 8140274
TI  - Cardiovascular and renal functional effects of an antagonist of the guanylyl
      cyclase-linked ANF receptor.
AB  - A selective antagonist for the cGMP-linked ANF receptor was used to assess
      inhibition of cardiovascular and renal actions of atrial natriuretic factor
      (ANF). Two groups of anesthetized rats were injected with antagonist or vehicle,
      respectively, prior to an infusion of ANF. A third group received neither
      antagonist injection nor ANF infusion and served as a time control. Compared to
      ANF infusion alone, prior antagonist administration was associated with
      significant reduction of both the hypotension and hemoconcentration following
      peptide infusion, although significant residual effects were still present.
      Glomerular filtration rates during ANF infusion were significantly lower in the
      antagonist group. The increases in urinary salt and water excretion were also
      partially blocked by the antagonist. Microcatheterization studies showed
      significant partial reversal of ANF-induced inhibition of sodium chloride and
      water reabsorption in the medullary collecting duct. We conclude that the
      antagonist is an effective specific blocker of the cardiovascular, renal
      hemodynamic, and tubular effects of ANF, providing a useful new tool to elucidate
      the regulatory roles of this peptide hormone system.

PMID- 8140275
TI  - Identification of immunoreactive atrial natriuretic peptide in the gallbladder
      and bile juice of rabbit, pig and human.
AB  - The presence of immunoreactive atrial natriuretic peptide (irANP) in rabbit, pig
      and human gallbladders was investigated using radioimmunoassay and
      immunohistochemistry. Serial dilution curves of gallbladder tissue and bile juice
      extracts were paralleled to the standard curve of atriopeptin III. Gel filtration
      profiles of gallbladder tissue extracts showed a major peak corresponding to rat
      pro-ANP. The amounts of irANP in rabbit, pig and human gallbladders were 30.0 +/-
      12.3 pg/mg (n = 7), 7.0 +/- 2.0 fg/mg (n = 7) and 17.7 +/- 2.0 fg/mg wet tissue
      (n = 8), respectively. Bile juice was also shown to contain irANP but with small
      molecular mass. The amounts of irANP in the rabbit, pig and human bile juice were
      25.0 +/- 2.0 (n = 7) and 0.50 +/- 0.02 (n = 7), and 1.3 +/- 0.1 pg/ml (n = 8),
      respectively. The immunohistochemical staining of the rabbit gallbladder tissue
      revealed the presence of irANP in the luminal epithelium and smooth muscle layer.
      The amount of irANP was higher in the luminal epithelium than in the rest of the
      gallbladder tissue from rabbits (0.30 +/- 0.06 vs. 0.01 +/- 0.01 pg/microgram
      protein, P < 0.01). These findings suggest that ANP may be synthesized and stored
      in the gallbladder, and may have a role in the regulation of fluid balance and
      cystic motility.

PMID- 8140276
TI  - Selective constriction of small cutaneous arteries by NPY matches distribution of
      NPY in sympathetic axons.
AB  - This study has begun to investigate some functional implications of the
      differential localization of neuropeptide Y (NPY) in sympathetic neurons
      supplying different arterial segments in the cutaneous circulation of the guinea
      pig ear. Responses of the main ear artery to exogenous NPY and norepinephrine
      (NE) were examined in vitro by measuring isometric tension. Responses of smaller
      arterial vessels to application of exogenous NPY or NE to the adventitial surface
      were examined in anaesthetized, ventilated guinea-pigs, by measuring changes in
      internal vessel diameter using video microscopy. Some arterial segments
      subsequently were examined for the presence of immunoreactivity (IR) to tyrosine
      hydroxylase (TH) and NPY. NPY (1 nM-10 microM) contracted the main ear artery
      (EC50 = 10 nM; max. contraction = 30% KCl), and 1 nM NPY produced slight
      potentiation of contractions produced by NE. In vivo, local applications of NPY
      (1-10 microM) constricted only a subpopulation of arterial vessels (23 of 41).
      All vessels constricted by NPY were innervated by axons containing IR to both TH
      and NPY, and as a population, were more proximal in the arterial tree (branch
      orders 3 to 6) than were vessels insensitive to NPY (branch orders 4 to 8). Most
      vessels insensitive to NPY were arterioles and arterio-venous anastomoses < 40
      microns in diameter, which were innervated by axons containing TH-IR but not NPY
      IR. In contrast, local application of NE (1-30 microM) constricted all vessels
      examined in vivo. When present, NPY constrictions had a longer latency (15-45 s)
      and duration (3-4 min) than NE constrictions of the same vessel segments. In
      vivo, NPY sometimes potentiated the peak amplitude of NE constrictions (2 of 7
      vessels), but only in vessels where NPY also produced direct constriction. These
      results reveal an excellent correlation between the localization of NPY in
      sympathetic axons, and the location of postsynaptic NPY receptors throughout the
      cutaneous arterial system. Any NPY released in response to strong activation of
      cutaneous sympathetic neurons is likely to act preferentially on the proximal
      cutaneous arteries, and to lead to a more prolonged constriction of these
      arteries than of more distal arterioles and arterio-venous anastomoses.

PMID- 8140277
TI  - The mechanism of action of gastrin releasing peptide (GRP) in stimulating avian
      gastric acid secretion.
AB  - The mechanisms of action of gastrin and gastrin releasing peptide (GRP) in
      stimulating gastric acid secretion were examined in the anaesthetized turkey.
      Gastrin and GRP produced dose-dependent increases in acid secretion that were
      inhibited by the gastrin/CCK-B antagonist CI988. The antagonist did not affect
      the acid secretory responses to histamine or carbachol. A GRP antagonist
      (M216140) inhibited the acid response to GRP, but not gastrin. The results
      suggest that in birds, GRP stimulates acid secretion by release of gastrin, which
      acts in turn on classical gastrin/CCK-B receptors in the proventriculus.

PMID- 8140278
TI  - Immunogold labelling of Listeria monocytogenes virulence-related factors within
      Caco-2 cells.
AB  - We demonstrated by immunoelectron microscopy that listeriolysin O (LLO),
      phospholipases and other putative virulence-related proteins produced by Listeria
      monocytogenes were primarily cell-wall-associated when the bacterium infected
      Caco-2 tissue culture cell monolayers. Antibodies made to LLO, serogroup 1/2a
      reacted poorly with serogroup 4b cells and vice-versa, indicating fundamental
      structural differences in the two proteins. Finally, comet-tail pseudopod
      structures shown to be involved in cell-to-cell passage of Listeria in Caco-2
      cells did not possess detectable Listeria antigens on their anterior surface or
      within their structure, suggesting that the phagocytic process is primarily host
      cell-dependent once it is initiated by the bacterial cell.

PMID- 8140279
TI  - Correlation between changes in surface hydrophobicity and interaction of
      Streptococcus pyogenes with human polymorphonuclear leukocytes after prolonged
      starvation in sea water.
AB  - The aim of this research was to evaluate the persistence of virulence
      characteristics of Streptococcus pyogenes cells after prolonged starvation in sea
      water. Studies were carried out on changes in viability, alterations in the
      chemical composition and surface hydrophobicity and the interaction of S.
      pyogenes with human polymorphonuclear leukocytes (PMN) after starvation. Results
      showed that surface hydrophobicity decreased progressively starting after three
      days of starvation and was correlated with the decrease in total carbohydrate,
      lipid and protein content. These values correlated with a better interaction of
      S. pyogenes cells with the PMN, as shown by a chemiluminescence increase that
      reached a peak after 32 days of starvation. Furthermore, bacterial cells became
      more easily phagocytized and killed by human PMN.

PMID- 8140281
TI  - Characterization of a temperate phage hosted by Alcaligenes eutrophus strain A5.
AB  - Nineteen strains of Alcaligenes eutrophus were tested for the presence of
      prophages. One strain that lysed upon mitomycin C treatment produced a phage
      which could not form plaques on any of the strains available. DNA extracted from
      partially purified phage lysates was digested with various restriction enzymes
      which showed that the 42 kb long viral double-stranded DNA circularizes by means
      of cohesive ends. To our knowledge, this is the first description of a phage for
      the genus Alcaligenes.

PMID- 8140280
TI  - Growth temperature controls the production of a single extracellular protease by
      Pseudomonas fluorescens MF0, in the presence of various inducers.
AB  - The psychotrophic strain Pseudomonas fluorescens MFO is known to express several
      enzymatic activities in milk, including extracellular proteolytic activity,
      optimally when cells are grown at 17.5 degrees C. In order to study the nature of
      the mechanisms controlling the production of the extracellular protease, we
      devised a defined medium in which this enzymatic activity was induced by an amino
      acid and small peptides. Regardless of the inducer, optimal proteolytic activity
      appeared at 17.5 degrees C. SDS-PAGE and isoelectrofocussing revealed a single
      protease produced by P. fluorescens MFO with all the inducers used and at all
      temperatures examined. The level of proteolytic activity correlated with the
      amount of enzyme in the supernatants.

PMID- 8140282
TI  - Novel bioactive compounds from Actinomycetes: a short review (1988-1992).
AB  - Novel secondary metabolites continue to be isolated from Actinomycetes. Their
      biological activities and chemical structures show a wide range of diversity.
      This short review provides information on the compounds isolated between 1988 and
      1992, and highlights interesting substances discovered during screening.

PMID- 8140283
TI  - Detection and identification of novel actinomycetes.
AB  - The actinomycetes are well known as a group of filamentous, Gram-positive
      bacteria that produce many useful secondary metabolites, including antibiotics
      and enzymes. Although they have been intensively studied for both theoretical and
      practical objectives, there is much scope for developing our basic knowledge of
      the means of detection and isolation of these microbes. This session concentrated
      on new methods for the detection and identification of novel actinomycetes from a
      range of environments. Approaches to the detection of actinomycetes ranged from
      investigations of neglected habitats and extreme environments (e.g. alkaline
      soils and oil drills) to the analysis of DNA extracted from the environment and
      use of specific phages. The continuing problems of the identification of
      actinomycete isolates were also considered. Topics discussed included use of
      phage typing, DNA probes, and correlation between phenetic and genotypic species
      of Streptomyces.

PMID- 8140284
TI  - Physiology of some actinomycete genera.
AB  - Actinomycetes are widespread in the environment and are mainly organotrophic.
      Studies of their ecology have been primarily focussed on their detection and
      isolation, with comparatively little attention to the control mechanisms that
      determine their occurrence and behaviour in their natural environments. This
      session provided some diverse examples of approaches to this problem. Several
      actinomycete genera produce motile spores. The significance of flagella proteins
      and factors influencing spore motility and germination are considered. The genus
      Frankia forms nitrogen-fixing associations with non-leguminous plants. Molecular
      techniques have been used to clarify the endophyte-host relationships.
      Micromonospora species are common in the environment. The growth and physiology
      of a gentamicin-producing strain are described. Thermophilic actinomycetes in the
      genus Thermoactinomyces are common in composts and other self-heating
      environments. Novel isolates from acid soil, which grow and produce enzymes
      active at high temperatures and in acidic conditions, are discussed.

PMID- 8140285
TI  - Physiology and genetics of antibiotic production and resistance.
AB  - Actinomycetes have the genetic capability to synthesize many different
      biologically active secondary metabolites and of these compounds, antibiotics
      predominate in therapeutic and commercial importance. Intensive research often
      centres on the use of molecular techniques to investigate the physiology and
      genetics of antibiotic biosynthesis with a view to improving production. The
      isolation of clones of Streptomyces hygroscopicus, the producer of geldanamycin,
      which synthesizes geldanamycin in S. lividans, is reported. Molecular approaches
      using genes for elongation factors (tuf) were used in attempts to increase the
      fermentation yield of kirromycin, whilst probes for aphD and sph, genes for
      streptomycin phosphotransferases, were used to gather information on streptomycin
      genes in soil. Actinomycete populations in soil and earthworms may help in
      developing a strategy for discovering additional antimicrobials in soil. The
      relationship of proline metabolism to the secondary metabolite undecylprodigiosin
      and the carbon regulation of spiramycin biosynthesis in S. ambofaciens is also
      reported.

PMID- 8140286
TI  - Expansion of the mitochondrial carrier family.

PMID- 8140287
TI  - Progress towards a higher taxonomy of viruses.
AB  - The current consensus view is that a higher hierarchical taxonomy of viruses
      cannot be established for two reasons. Firstly, viruses appear to be polyphyletic
      in origin, with several sets of viruses arising by different, independent routes
      at different times. Secondly, subsequent virus adaptation for survival in
      different host/vector combinations has involved the selective acquisition of
      additional genes by a process of cassette or modular evolution, with these
      additional gene modules coming from other viruses or host genetic material. Thus,
      depending on the gene product used for comparison, different phylogenetic
      relationships can be deduced. Further virus adaptation can arise by reassortment
      of segmented genomes, gene duplication, deletions, frameshift mutations, point
      mutations or de novo development of new gene products from existing, unused
      reading frames. The solution to the first objection is to place all viruses in a
      separate kingdom and assign the current viruses to several phyla that reflect
      these diverse origins. The solution to the second objection is to consider the
      core module of replication machinery as the major criterion on which to make the
      initial assignments to classes and orders. For RNA viruses, the major criterion
      is the sequence identity of the RNA-dependent RNA polymerase. Using this
      criterion, the positive strand RNA viruses can be assigned to five classes that
      correspond to the recently recognized supergroups of RNA viruses. These five
      classes contain four, three, three, three and one order(s) respectively. These
      fourteen orders contain 31 virus families (including 17 families of plant
      viruses) and 48 genera (including 30 genera of plant viruses). This approach
      confirms the separation of the alphaviruses and flaviviruses into two families,
      the Togaviridae and Flaviridae, but suggests that several other current taxonomic
      assignments, such as the pestiviruses, hepatitis C virus, rubiviruses, hepatitis
      E virus and arteriviruses, may be wrong. The coronaviruses and toroviruses appear
      to be distinct families in distinct orders, not distinct genera of the same
      family as currently classified. In addition, the luteoviruses are split into two
      families and apple chlorotic leaf spot virus appears not to be a closterovirus
      but a new genus of the Potexviridae. From an analysis of the polymerase
      dendrograms of the dsRNA viruses, it appears that they are not closely related to
      each other, but belong to four additional classes (Partitiviridae, Reoviridae,
      Birnaviridae and Cystoviridae) and one additional order (Totiviridae) of one of
      the classes of positive ssRNA viruses in the same subphylum as the positive
      strand RNA viruses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8140289
TI  - Expression of the non-structural proteins of parvovirus MVMp from recombinant
      retroviruses: predominant role of the parvoviral NS-1 product in host cell
      disturbance.
AB  - Stable Psi-2 cell transformants were selected for their resistance to neomycin
      after transfection with a retroviral pZipNeo-SVX vector carrying sequences
      encoding for the non-structural proteins of parvovirus minute virus of mice
      (prototype strain, MVMp). Cells producing both NS-1 and NS-2 proteins (PsiNS) or
      only the NS-2 polypeptide (PsiNS2) were obtained. PsiNS cells exhibited
      morphological abnormalities and had a reduced clone-forming ability, whereas
      PsiNS2 cells were indistinguishable from the parental line. These cellular
      systems produced recombinant retroviral particles which transduced the NS gene(s)
      into mouse A9 cells. As in the case of Psi-2 cells, A9 transformants expressing
      both NS-1 and NS-2 proteins were impaired in their cloning efficiency. These
      results provided a direct confirmation of the predominant role of protein NS-1 in
      the cytopathic effect of parvoviruses.

PMID- 8140288
TI  - Genomic relatedness of five equine rotavirus strains with different G serotype
      and P type specificities.
AB  - Overall genomic relatedness among five equine rotavirus strains and their
      relatedness to representative human and animal rotavirus strains were
      investigated by RNA-RNA hybridization tests. The genomes of strains FI-14, FI-23
      and H2 were highly related to one another. Strain L338 had only a low degree of
      genomic relatedness to the other four equine rotavirus strains. Strain H1 also
      showed little genetic relatedness to the other equine strains. The genome of the
      strain H1, however, was highly related to those of porcine rotavirus strains OSU,
      Gottfried and YM. Genomic relatedness of four equine rotavirus strains (FI-14, FI
      23, H2 and L338) to human and other animal rotavirus strains was low, whereas
      several RNA segments of strain H1 showed a relatedness to those of human strain
      Wa.

PMID- 8140290
TI  - Analysis of neutralizing antibody specificities of different strains of
      lymphocytic choriomeningitis virus with strain-specific immune sera.
AB  - The present study was aimed at comparing specificities and cross-reactivities of
      immune mouse sera obtained from mice infected with a low (2 x 10(2) or 20
      immunological infectious focus units (ifu) or high (2 x 10(6) ifu) dose of
      various strains of lymphocytic choriomeningitis virus (LCMV). Neutralization
      titres of the various antisera were determined by an infectious focus reduction
      assay. This assay was performed on MC57G and on Vero E6 cells using the commonly
      utilized laboratory strains of LCMV WE, Docile, Armstrong, Armstrong Clone 13,
      Pasteur, Traub and Aggressive. Experiments with immune sera revealed broad cross
      neutralization, demonstrating a variable but close serological relationship
      between the various strains of LCMV.

PMID- 8140291
TI  - An attempt to identify gene products related to the induction of an antiviral
      state in macrophages resistant and sensitive to IFN-gamma.
AB  - The activation of bone-marrow-derived macrophages by IFN-gamma (IFN gamma)
      partially inhibits mouse hepatitis virus 3 (MHV3) replication only in cells from
      resistant A/J mice, and not in cells originating from susceptible BALB/c mice.
      The computer image analysis of gels obtained from 2D-SDS-PAGE of extracted
      proteins of IFN gamma-activated A/J or BALB/c macrophages enabled us to identify
      and tag several gene products that were synthesized at elevated or diminished
      levels. Comparisons of the patterns of non-activated and IFN gamma-activated A/J
      macrophages revealed 3 gene products which increased, 1 which newly appeared, 6
      which decreased and 20 which disappeared upon IFN gamma activation. The protein
      pattern of BALB/c macrophages revealed 13 gene products which increased, 8 which
      decreased and 8 which disappeared in IFN gamma-activated BALB/c macrophages.
      Whether these proteins are involved in the induction of an antiviral state
      against MHV3 growth remains to be investigated. Macrophages from mice with
      different genetic background (A/J and BALB/c), upon IFN gamma activation, behave
      differently at a molecular level, and this observation is consistent with their
      distinct expression of antiviral state against MHV3.

PMID- 8140293
TI  - Assessment of disease activity in sarcoidosis: deeds and misdeeds.

PMID- 8140292
TI  - Spermatozoa as potential carriers of HIV.
AB  - In order to investigate the role of germ cells in the sexual transmission of
      immunodeficiency virus (HIV), spermatozoa from healthy HIV-seronegative men were
      incubated in vitro with HIV1. After washing, they were cocultured with peripheral
      blood leukocytes from seronegative blood donors. Reverse transcriptase assays and
      p24 antigen tests were performed in culture supernatants. Electron microscopy
      examination of these HIV-incubated spermatozoa was carried out, as well as the
      search for CD4 molecules on their surface. Although virus bound to and seemed to
      enter spermatozoa despite the absence of detectable CD4 epitopes on their
      surface, no replication of HIV was apparent. However, HIV particles on the
      surface of spermatozoa were capable of infecting CD4 T lymphocytes. Present
      results would seem to preclude artificial insemination between an HIV
      seropositive man and an HIV-seronegative woman.

PMID- 8140294
TI  - Pulmonary Langerhans' cell granulomatosis (LCG).
AB  - Pulmonary Langerhans' granulomatosis (LCG) is characterised by infiltration of
      peripheral airways by dendritic cell precursors and Langerhans' cells (LC)
      together with eosinophils and mixed chronic inflammatory cells. Consequent
      airways destruction commonly leads to cystic changes and frequent pneumothorax.
      LC's are best identified by the electron microscope finding of Birbeck granules.
      Immunocytochemical markers are also of value. They are frequent in the early
      stages though absent in end stage disease. LCG is distinguished from sarcoidosis
      by the absence of epithelioid cell granulomas, association with heavy cigarette
      smoking in young males and frequency of pneumothorax. Both diseases show
      lymphocytosis in bronchoalveolar lavage but differ in that LCG shows a
      predominance of T-suppressor cells and sarcoidosis an excess of T-helper cells.

PMID- 8140295
TI  - Imparied interferon-gamma production by peripheral blood mononuclear cells and
      effects of calcitriol in pulmonary sarcoidosis.
AB  - Pulmonary sarcoidosis (S) is a granulomatous disease of unknown etiology
      characterized by spontaneous release of cytokines and 1,25-dihydroxyvitamin D3
      (calcitriol) at the sites of granulomatous reaction. Stimulated by our previous
      findings that high levels of interferon-gamma (IFN-gamma) occur in this disease
      and that calcitriol reduces IFN-gamma production by peripheral blood mononuclear
      cells (PBMC) from normal subjects, we designed the present study to evaluate IFN
      gamma production and the effect of calcitriol on the release of this cytokine by
      PBMC in S patients. The cells were stimulated with staphylococcal enterotoxin A
      (SEA) and A23187 calcium ionophore. Our results show that SEA- and A23187
      stimulated PBMC from patients with S released significantly less IFN-gamma than
      those from control subjects. Calcitriol at 10(-6) M and 10(-9) M concentrations
      reduced IFN-gamma production by SEA-stimulated PBMC but this inhibitory effect
      was lower in S patients than controls. With A23187 we observed different
      behaviour at the various doses: at low doses calcitriol was as effective as in
      controls, but at 10(-6) M it was significantly less inhibitory in S than in
      healthy subjects.

PMID- 8140296
TI  - The development of airways obstruction in sarcoidosis among smokers and non
      smokers.
AB  - The prevalence of respiratory function abnormalities was studied in 32 patients
      with pulmonary sarcoidosis, 16 (50%) of whom were smokers. Airflow obstruction
      was found at presentation in one non-smoker and developed in four more during the
      course of follow-up. Similar airflow obstruction was present in six smoking
      patients and developed in four patients subsequently. Airways obstruction was a
      common physiological defect even in non-smokers, though smokers had more frequent
      airflow obstruction and developed a worse defect.

PMID- 8140297
TI  - Psychological factors in sarcoidosis: the relationship between life stress and
      pulmonary function.
AB  - Seventeen patients with diagnosed sarcoidosis were administered a number of
      psychological instruments to assess anxiety, depression, life stress, and
      symptoms of agoraphobia and/or panic. These patients were then followed medically
      for a period of nine months. Scores on the various psychological tests were then
      compared with results obtained from repeated pulmonary function tests. Results
      showed a consistent relationship between increased life stress at time one and
      impairment in lung function throughout the study period. In addition, no
      consistent set of psychiatric symptoms were associated with the disease. Sarcoid
      patients did, however, report many symptoms similar to patients with agoraphobia.
      These results are discussed in terms of the potential benefits of stress
      reduction treatment as an adjunctive therapy for patients with sarcoidosis.

PMID- 8140298
TI  - Recurrent Lofgren's syndrome in three patients with sarcoidosis.
AB  - Lofgren's syndrome (acute onset of sarcoidosis with erythema nodosum, arthritis,
      sometimes fever and bilateral hilar lymphoma) is a well known clinical entity.
      Recurrent Lofgren's syndrome is, however, extremely rare. We report three cases
      of recurrent Lofgren's syndrome. The duration between the first manifestation of
      the syndrome and the first relapse varied between two and eight years. One of the
      patients had two relapses, two and six years after the initial onset of disease.

PMID- 8140299
TI  - Sarcoid-like granulomas in primary renal cell carcinoma.
AB  - A case of renal cell carcinoma containing non-caseating epithelioid granulomas is
      described. These granulomas were indistinguishable from sarcoid granulomas
      microscopically. There was a clinical suggestion of sarcoidosis thirteen years
      prior to the excision of the tumour. The pathogenesis and significance of tumour
      associated epithelioid granulomas are discussed.

PMID- 8140300
TI  - Familial Mediterranean fever. Another cause of raised serum angiotensin
      converting enzyme; another abortive attempt at masquerading as sarcoidosis.

PMID- 8140301
TI  - Sarcoidosis complicated by non-Hodgkin's lymphoma. Report of a case.
AB  - A 31-year-old male who had suffered from sarcoidosis since the age of eight
      developed non-Hodgkin's lymphoma 23 years after the sarcoidosis was diagnosed.
      During the course of chemotherapy the patient developed hepatic failure and died
      of pulmonary hemorrhages. This appeared to be a case of the sarcoidosis-lymphoma
      syndrome first described by Brincker and which has been rarely reported in Japan.
      We review the literature on this disorder and the immunologic abnormalities
      considered to participate in the lesions.

PMID- 8140302
TI  - Sarcoidosis--the way ahead.
AB  - The cause(s) of sarcoidosis is likely to be a combination of a conducive soil or
      sarcoid diathesis invaded by an antigen-driven cell-mediated immune response. The
      antigenic invasion may be mycobacteria and other organisms and/or their chemical
      constituents. A ten-point plan of management is set out so that early diagnosis
      allows early treatment and to prevent complicating pulmonary, ocular or renal
      fibrosis and to prevent failure of these vital organs.

PMID- 8140303
TI  - Alveolar inflammation in pulmonary sarcoidosis: cells and mediators.

PMID- 8140304
TI  - Synthesis and release of granulocyte--macrophage colony--stimulating factor by
      alveolar macrophages of patients with sarcoidosis.

PMID- 8140305
TI  - Interferon gamma and sarcoidosis.

PMID- 8140307
TI  - HLA Class I, II and III polymorphisms in sarcoidosis.

PMID- 8140306
TI  - Calcium-phosphorus metabolism in sarcoidosis.

PMID- 8140308
TI  - Immunohistochemical detection of microenvironmental abnormalities in lung
      biopsies from patients with sarcoidosis.

PMID- 8140309
TI  - Why perform high resolution computed tomography in pulmonary sarcoidosis?

PMID- 8140310
TI  - 67 Ga scan, symptoms and treatment in sarcoidosis.

PMID- 8140311
TI  - Phonopneumographic findings in patients with sarcoidosis and lung fibrosis.

PMID- 8140312
TI  - Sarcoid extrapulmonary features. Shift of the bioptic approach from the
      mediastinoscopy to the pleuroscopy.

PMID- 8140313
TI  - Eye involvement in sarcoidosis: survey of 197 patients.

PMID- 8140314
TI  - Clinical and histopathological aspects of atypical cutaneous manifestations of
      sarcoidosis.

PMID- 8140315
TI  - Rheumatic manifestations of sarcoidosis.

PMID- 8140316
TI  - Alterations in calcium metabolism and bone mineral density in relation to the
      activity of sarcoidosis.

PMID- 8140317
TI  - Alveolar and circulating CD8+ lymphocyte subsets in pulmonary sarcoidosis.

PMID- 8140318
TI  - Analysis of alveolar and peripheral CD45RO+ T-lymphocytes in sarcoidosis.

PMID- 8140319
TI  - Selection of Valpha 2.3 cells in the lung of patients with sarcoidosis.

PMID- 8140320
TI  - The T-cell antigen receptor repertoire of alpha beta+ T-lymphocytes in patients
      with tuberculosis.

PMID- 8140321
TI  - Diagnostic and prognostic applications of flow cytometry in pleuro-pulmonary
      neoplasms.

PMID- 8140322
TI  - Gamma/delta T-lymphocytes in advanced pulmonary asbestosis.

PMID- 8140323
TI  - Role of the HLA-DP gene in susceptibility to lung granulomas.

PMID- 8140324
TI  - Role of high-resolution CT in the diagnosis and evaluation of pulmonary
      sarcoidosis.

PMID- 8140325
TI  - Role of magnetic resonance imaging in neurosarcoidosis.
AB  - Central nervous system (CNS) involvement in Sarcoidosis poses a difficult
      diagnostic problem for the clinician. Neurologic involvement may occur long
      before the onset of symptoms. Contrast enhanced computerized tomography does not
      always reveal parenchymal and meningeal involvement. Recently gadolinium enhanced
      Magnetic Resonance Imaging has shown increased sensitivity in detecting CNS
      involvement. These findings however are not specific for sarcoidosis and one must
      consider appropriate clinical circumstances in arriving at the diagnosis.

PMID- 8140326
TI  - Epithelioid sarcoma: a clinicopathologic and prognostic study of 26 cases.
AB  - Twenty-six cases of epithelioid sarcoma having a minimum of 5 years follow-up are
      presented. The patients ranged in age from 11 to 64 years; 18 were between 20 and
      40 years of age. Males predominated (18:8). The most common tumor locations were
      the fingers (6 cases), the wrist (5 cases), and the hand (4 cases). All tumors
      were typical histologically, with medium-sized to large epithelioid and plump
      spindle cells, a predominantly nodular growth pattern, and intranodular collagen.
      Features seen in a minority of cases included hyalinized collagen, calcification,
      myxoid areas, and focal small cells. The major factor related to distant
      metastasis and death from tumor proved to be tumor size; all 7 patients with
      neoplasms > or = 5 cm died of tumor, and 6 had distant metastases, whereas only 2
      of 10 patients with smaller tumors developed distant metastases and died (of
      patients with neoplasms of unknown size, 3 died of tumor and 2 of those along
      with 1 other had distant metastases). Five patients had regional lymph nodes
      involved (4 with tumors > or = 5 cm, 1 with tumor of unknown size), and all died.
      Local recurrence was primarily associated with treatment by excision alone (9 of
      10 cases) rather than amputation (2 of 8 cases) or excision and radiation (2 of 8
      cases); recurrences were often controlled by subsequent amputation. When tumor
      size and treatment were taken into account, histological variables including
      mitotic rate, tumor necrosis, and perineural invasion were not significantly
      related to recurrence, metastasis, or patient survival.

PMID- 8140327
TI  - Disease recurrence after orthotopic liver transplantation.
AB  - With the advent of cyclosporine immunosuppression in the late 1970s, liver
      transplantation became a widespread modality for the treatment of end-stage liver
      disease. Several metabolic disorders that produce liver injury, such as Wilson's
      disease and alpha-1-antitrypsin deficiency, are cured by liver transplantation.
      However, many other diseases for which transplantation is undertaken may recur in
      the allograft. As follow-up increases and newer diagnostic modalities become
      available, those diseases that recur, and their natural histories, are becoming
      better understood. This new information may lead to a reevaluation of the
      suitability of some conditions for transplantation. This article briefly reviews
      disease recurrence in orthotopic liver transplants.

PMID- 8140328
TI  - Functional pathology of urinary bladder muscularis: the new frontier in
      diagnostic uropathology.
AB  - Disorders of micturition (voiding dysfunction), the essence of urinary bladder
      function, are unknown to the discipline of pathology, despite their prevalence
      and profound socioeconomic impact. Their pathogenesis has remained largely
      unknown, their diagnosis often difficult or uncertain, and the outcome of their
      management generally unpredictable. A new approach to morphologic study of the
      bladder has been developed to identify microstructural correlates of its
      function. Application of this approach to endoscopic biopsies culminated in the
      concept of functional pathology of urinary bladder muscularis. The basis,
      elements, current status, and diagnostic potential of this new concept are
      presented in relation to the major forms of clinical voiding dysfunction.

PMID- 8140330
TI  - [Capsular polysaccharide of Klebsiella pneumoniae. II. Immunogenic properties].
AB  - It has been considered that the polysaccharide capsular material from
      microorganisms such as Klebsiella pneumoniae induces mainly thymus-independent
      humoral immunity, nevertheless studies done with Bacteroides fragilis have shown
      the participation of cellular immune effector mechanisms. Works done to define
      the immunogenic role of the capsular polysaccharide of Klebsiella pneumoniae
      indicate that both active and passive immunization with these antigens confer
      protection against infections with this bacteria. Several studies propose the use
      of vaccines prepared with one or various capsular serotypes of Klebsiella
      pneumoniae in immunoprophylaxis or immunotherapy.

PMID- 8140329
TI  - [Antimicrobial activity of human colostrum against enteropathogens. Preliminary
      study].
AB  - The antimicrobial activity of the colostrum serum from ten women has been
      evaluated. The activity against Escherichia coli, Shigella sonnei and Klebsiella
      pneumonia at three different bacterial populations was determined (1 x 10(4), 1 x
      10(5) and 1 x 10(6) UFC/ml). Antimicrobial activity against the three strains was
      found. Bactericidal activity was observed to inocula of 1 x 10(4) UFC/ml in 8/10
      sera against E. coli, in 6/10 sera against S. sonnei, and in 3/10 sera against K.
      pneumonia; in the rest of the cases, sera were bacteriostatic. With inocula of 1
      x 10(5) UFC/ml there was bactericidal activity in 4/10 sera against E. coli and
      S. sonnei and in 1/10 against K. pneumonia. Lastly, with inocula of 1 x 10(6)
      UFC/ml there was bactericidal activity in 4/10 sera against E. coli, 1/10 against
      S. sonnei and none against K. pneumoniae. The results suggest that because of the
      antimicrobial properties of human milk the risk of intestinal infections by
      enteropathogens is less.

PMID- 8140331
TI  - [Repair mechanisms of damaged deoxyribonucleic acid molecules].
AB  - The importance of the DNA-damage repair mechanisms comes from the fact that any
      chemical modification to the DNA molecule, no matter how small it is, very often
      causes cell death and sometimes it can produce mutations whose biological effects
      are unpredictable. Taking into account that in the last decade great advances
      have been reported for the understanding of these mechanisms, and this knowledge
      can be essential to reach the control of the mutagenesis, we give a current
      review of the main DNA-damage repair pathways, with special emphasis in its
      classification by the kind of mechanisms and in their main features. As a
      particular case, the error prone repair mechanism is included (SOS-REPAIR).
      Additionally the three inducible DNA repair systems are described. That is to
      say, those cases in which the cell treatment with sublethal doses of some
      physical or chemical agents, induces a cell response that increases its capacity
      to repair the DNA-damage causes by higher doses of the same agent. Finally some
      small general comments are made.

PMID- 8140333
TI  - [Proteases from Pseudomonas: immunologic comparison].
AB  - We studied 5 strains of Pseudomonas fluorescens, its ability to produce
      proteolytic enzymes and the antigenic relatedness between P. fluorescens and P.
      aeruginosa proteases. Cells were grown in tryptic soy broth plus 2% skim milk
      powder, at 4 C during 5 days. All the proteases acted on gelatin, casein, and
      showed limited activity on congo redelastin. By zymograms in polyacrylamide gel
      (PAA), one enzyme responsible of whole enzymatic activity was shown. The
      extracellular protease of the strain P. fluorescens ATCC 17400 was purified by
      ammonium sulfate precipitation (60% saturation) and chromatography on DEAE
      cellulose with ionic strength gradient, and Sephadex G 100. A 181 fold increase
      in specific activity with a recovery of 21% was obtained. PAA-sodium dodecyl
      sulfate revealed a single band with a molecular weight of approximately 45,700 +/
      1,000 Daltons. P. fluorescens antiprotease rabbit serum showed by
      immunodiffusion (ID) and countercurrent immunoelectrophoresis (CIEF) identity
      pattern of reaction with the homology strains studied. Rabbit sera antielastase
      and anti-alkaline protease of P. aeruginosa did not exhibit by ID, CIEF and
      immunoblotting immunological reactivity with antigen (protease) from P.
      fluorescens; by enzyme linked immunosorbent assay (ELISA), P. aeruginosa
      antielastase rabbit serum showed a weak response with P. fluorescens protease.
      These preliminary observations showed analogy in enzymatic functions, such as
      specificity, between the enzymes produced by phylogenetically related species,
      but the immunological studies showed very little interspecific homology.

PMID- 8140332
TI  - [Isolation of Campylobacter jejuni ATCC 29428 from inoculated fried pork meat and
      roasted chicken].
AB  - The human gastroenteritis caused by Campylobacter jejuni in some industrialized
      countries is higher than gastroenteritis produced by Salmonella and Shigella.
      This has induced the development of techniques to demonstrate the presence of the
      microorganism in different foods using some culture media combinations. There is
      not a method to isolate C. jejuni from roasted chicken and fried pork meat, which
      are popular foods in Mexico. The sensitivity of two culture media combinations
      was compared: Rama broth (RB)-Rama agar (RA) and Preston broth (PB)-Skirrow agar
      (SA) to isolate C. jejuni from these foods. The RB-RA combination demonstrated to
      be the best one to isolate C. jejuni.

PMID- 8140334
TI  - Lambda prophage decreases Escherichia coli sensitivity to human serum
      bactericidal effect.
AB  - Escherichia coli C600 and C600(lambda) strains were tested for their
      susceptibility to the bactericidal action of 4% normal human serum. C600 survival
      was reduced to 30%, 23% and 16% after 60, 150 and 180 min of exposure to serum,
      respectively, whereas the percentage of survival of C600(lambda) was 199, 109 and
      65% at the same times. The estimated exposition times for 50% killing showed an
      eight-fold difference, they were 23 and 202 min for C600 and C600(lambda),
      respectively. None of the two strains tested was killed when incubated with serum
      whose alternative complement pathway was inactivated by heating at 50 degrees C
      for 20 min, showing that this pathway, and not the classical one, was responsible
      of the bactericidal action, a conclusion further supported by the finding that
      both strains were differentially killed by the alternative complement pathway,
      C600 showing a 14X, 10X and 4X greater susceptibility than C600(lambda) at 60,
      120 and 180 min of exposure to serum whose classical pathway was selectively
      inhibited by chelation with 10 mM EGTA plus 2 mM MgCl2. We feel that lambda phage
      may lower the serum sensitivity of its lysogen by altering the bacterial external
      surface, perhaps by the inclusion of some protein encoded by an accessory gene of
      the lambda genome, and thus interfering with either the formation, deposition or
      activity of the membrane attack complex.

PMID- 8140335
TI  - Behavior of Escherichia coli R factors in Salmonella typhi.
AB  - Seventeen R factors originally found in community-isolated E. coli strains were
      transferred by in vitro conjugation experiments to three S. typhi strains and to
      J55, an E. coli J53 pro met derivative strain, in order to analyze R factor
      stability through 100 generations in liquid cultures at low bacterial density
      thus avoiding R factor retransfer. Four R factors were maintained in 100% of the
      S. typhi colonies tested after 100 generations. Four other R factors were
      completely or almost completely segregated, and nine R factors showed an
      intermediate segregation rate (average 50%). Resistance stability rate in J55 was
      high (above 90%) as was expected. Overall R factors in S. typhi tend to
      segregation and this may partially explain epidemiological data about low
      antibiotic-resistance incidence in S. typhi.

PMID- 8140336
TI  - [Detection of TEM-beta-lactamase in strains of Haemophilus influenzae resistant
      to ampicillin using the polymerase chain reaction (PCR)].
AB  - With the purpose of determining the type of beta-lactamases that mediate
      ampicillin resistance to in Haemophilus influenzae strains in the Hospital
      Infantil de Mexico "Federico Gomez", we determined the minimum inhibitory
      concentration of 180 strains, isolated from different sources, to ampicillin,
      amoxicillin-clavulanic acid and ampicillin-sulbactam. All ampicillin resistant
      strains (29) were beta-lactamase positive as determined by nitrocephin
      hydrolysis. Using PCR with the primers from pBR322, we detected the presence of
      the gene for the TEM-beta-lactamase in 100% of the ampicillin resistant strains.

PMID- 8140337
TI  - Some studies on the experimental infection of golden hamsters with Taenia solium.
AB  - Golden hamsters were infected orally with viable cysticerci of Taenia solium
      obtained from infected pigs. After two weeks of infection implanted scolices of
      about 4 mm were found in exactly the same number as the number of ingested
      cysticerci. At six weeks 66% of the ingested cysticerci were found as implanted
      tapeworms (average size: 5.7 cm). At ten weeks 16% of the ingested cysticerci
      were found as implanted tapeworms (average size: 5.8 cm). At 14 weeks no
      tapeworms were found. Skin tests with taenia extracts were positive after 9 weeks
      of infection peaked at 12 and 14 weeks and declined afterwards becoming negative
      after 27 weeks. Skin test with cysticercus extracts were weaker, peaked at 8 and
      10 weeks, were very low after 12 weeks and became negative after 16 weeks.
      Histological studies in the attachment site at the small intestine showed at 2
      weeks a cellular infiltrate formed by macrophages, epithelioid cells and some
      plasma cells, there was very little alteration of epithelium. At 6 and 8 weeks
      the epithelium was damaged and necrotized. At 17 and 19 weeks the lesion started
      to resolve. We conclude that the golden hamster can be used to reproduce in the
      laboratory at least part of the life cycle of Taenia solium.

PMID- 8140338
TI  - Utility of risk models for renal failure and critically ill patients.

PMID- 8140339
TI  - Novel mediators of sepsis-associated renal failure.

PMID- 8140340
TI  - Hemodynamic support: volume management and pharmacological cardiovascular
      support.

PMID- 8140341
TI  - Therapeutic strategies in the prevention of acute renal failure.
AB  - The current management of acute renal failure rests largely on the avoidance of
      ischemic and nephrotoxic insults, attention to fluid and electrolyte balance, and
      the use of dialytic procedures when necessary. The efficacy of several strategies
      in experimental renal disease, reviewed in this article, raises the possibility
      that available to the clinician in the not-too-distant future would be analogous
      interventions that interrupt pathways of tissue injury and/or summon processes
      that attenuate the damaging effect of a given insult. The implementation of such
      therapeutic modalities would expand the management of acute renal failure from
      its current conservative approach to one encompassing therapeutic interventions
      that potentially prevent the occurrence of acute renal failure. Moreover, the
      remarkable and ever-increasing understanding of acute renal failure, in all its
      deranged cell biology and complex pathogenesis, offers the promise of discerning
      still better and more effective therapeutic interventions.

PMID- 8140342
TI  - Nutritional care of the critically ill patient with renal failure.

PMID- 8140343
TI  - Therapeutic alternatives to renal replacement for critically ill patients in
      acute renal failure.

PMID- 8140344
TI  - Common fluid-electrolyte and acid-base problems in the intensive care unit:
      selected issues.

PMID- 8140345
TI  - Acute renal failure: directed therapy to enhance renal tubular regeneration.

PMID- 8140346
TI  - [Aging of the face].

PMID- 8140347
TI  - [The aging breast].

PMID- 8140349
TI  - [The nurse's role in the operating room].

PMID- 8140348
TI  - [Anesthesia and recovery after surgery of aging].

PMID- 8140350
TI  - [The role of the nurse in esthetic surgery].

PMID- 8140351
TI  - [Current development of plastic surgery].

PMID- 8140352
TI  - [2 oncology nurses in the midst of the Consulting Committee for the Protection of
      Persons in Biomedical Research].

PMID- 8140354
TI  - [Peritoneal dialysis].

PMID- 8140353
TI  - [Approaches to the kidney. Lumbar position].

PMID- 8140355
TI  - [The main methods of possible face correction].

PMID- 8140356
TI  - [Cerebral endoscopy: current and future applications].

PMID- 8140357
TI  - [Cutaneous vasculitis: how to recognize, interpret, treat it?].
AB  - Clinical and histopathological features of cutaneous vasculitis are presented by
      means of 14 case reports. Proof of vasculitis in skin biopsy consecutively
      demands for a search of a cause and of the extension of the vasculitic process in
      the sense of a systemic disease. The most frequent form of cutaneous vasculitis
      is hypersensitivity angiitis, a disease in which always an exogenous (drugs,
      infections) or an endogenous (malignant neoplasia, connective tissue disease)
      trigger should be sought if cutaneous vasculitis persists after removal or
      treatment of the suspected cause. Then, antihistaminic or--particularly in cases
      with systemic involvement--immunosuppressive drugs (corticosteroids or
      cyclophosphamide) should be considered.

PMID- 8140358
TI  - [The paradigm change in medical thinking].
AB  - Due to the rapid growth of basic knowledge in recent decades, a tremendous amount
      of superspecial scientific information is confronting us today. This overflow of
      new and often short-lived data is influencing in a considerable way the view and
      the management of all life sciences. On the basis of the change of paradigm in
      modern economic systems, also influencing management, we try to compare the
      particular components of these changes that occur in medical sciences, e.g. in
      pathophysiology, diagnostic investigations and therapy. Most of the paradigm
      components can be used for an analysis of the consequences of the rapid changes
      in the medical way of thinking. For this contemplation, selected cases of thyroid
      disorders have been chosen.

PMID- 8140359
TI  - [Jakob-Creutzfeldt disease].
AB  - Starting out from a case report about a 84-year-old woman changing from absolute
      inconspicuousness to complete senile dementia within a few months, the authors
      present a not very well known neuropsychiatric disorder: the Jakob-Creutzfeldt
      disease. In short, historical, morphological and symptomatological aspects and
      laboratory findings are discussed, and it is shown that the complex problem of
      etiology and pathogenesis still is not entirely understood. It is pointed out,
      that earlier therapeutical attempts have not led to a significant improvement.

PMID- 8140361
TI  - [Observations on the advent of abdominal surgery via laparoscopy].

PMID- 8140360
TI  - [Cough, vomiting, rapid weight loss].
AB  - A young male patient from Somalia presented with a productive cough since a few
      days, and he complained about vomiting after meals and a rapid loss of weight of
      20 kg. Endoscopic, radiological and clinical examinations revealed a broncho
      esophageal fistula. Further examinations showed mycobacterium tuberculosis as the
      underlying cause of the disease; a malignancy was excluded. Antituberculous
      treatment resulted in the loss of the present symptoms as well as in a clinical
      and endoscopic closure of the fistula.

PMID- 8140363
TI  - [Informatics in a regional hospital].

PMID- 8140362
TI  - [Human babesiosis: first case report in Switzerland].

PMID- 8140364
TI  - [Hospital pharmacy: partner in the health care team].
AB  - The hospital pharmacy is responsible for providing each patient with the required
      drug treatment. This goal can be fulfilled by constant adaptation of the
      pharmaceutical services to the needs of the medical and nursing staff, hospital
      administration and other technical services. The goals and the functional
      relationship between the different activities of a hospital pharmacy are
      reviewed. The specific organisation of the Sierre-Loeche hospital pharmacy is
      presented. Centralisation of some services of the district hospital pharmacy
      within the central pharmacy of the "Institut Central des Hopitaux Valaisans"
      provides the hospital with the required services. Pharmaceutical counseling based
      on a regular activity of the pharmacist within the health care team is a
      prerequisite to adapt organisation and services to the requirements of the
      clinical situation.

PMID- 8140365
TI  - [Consultant physician: liaison between patient, physician, hospital, insurance].

PMID- 8140366
TI  - [Critical ischemia (severe chronic ischemia)].

PMID- 8140367
TI  - [Chronic arterial insufficiency of the lower limbs. A choice of diagnostic
      studies and of treatments].

PMID- 8140368
TI  - [Long-term results of vascular surgery of the lower limbs].

PMID- 8140369
TI  - [Arterial pathology of the upper limbs: the surgeon's viewpoint].

PMID- 8140370
TI  - [Carotid pathology: diagnostic studies].

PMID- 8140371
TI  - [Carotid surgery. Why? For whom?].

PMID- 8140372
TI  - [Is cardiac auscultation outmoded?].

PMID- 8140373
TI  - [Kinematics and continuous elongation of the anterior cruciate ligament].

PMID- 8140374
TI  - [Debriefing: a preventive measure following an injury (apropos of recent
      example)].

PMID- 8140376
TI  - [Constructive apraxia].

PMID- 8140377
TI  - [Nutritional quality of the food served to residents of nursing homes. A survey
      in 40 establishments of the Vaud canton (November and December 1992)].

PMID- 8140375
TI  - [Chronic obstructive bronchopneumopathy, mitral valvulopathy and global cardiac
      insufficiency].
AB  - The case of a 61 year-old man is presented. This patient had a rheumatoid
      arthritis and a cardiac failure. Echocardiography and catheterization revealed a
      mitral valvulopathy, biventricular dysfunction and conduction abnormalities.
      Pericardial disease was also present. Differential diagnosis lead to the clinical
      diagnosis of rheumatoid non constrictive pericarditis, rheumatoid myocarditis,
      rheumatoid endocarditis and idiopathic calcification of the mitral valve. Anatomo
      pathologic findings consisted in rheumatoid pancarditis.

PMID- 8140378
TI  - [A protein, molecule of the year 1993].

PMID- 8140379
TI  - [Nocturnal obstructive apnea: a not-to-be-ignored nosological entity].

PMID- 8140380
TI  - MRI and plain radiographics in acute frontal sinus infections.
AB  - Twenty-seven patients with acute frontal sinusitis, collected during a 4-month
      period, were examined with plain radiographics and MRI both at the time of
      diagnosis and one month later. Findings in the frontal and ethmoidal sinuses were
      recorded. Frontal sinus trephination was performed in 13 of the 27 cases. The
      study shows that MRI is as reliable as X-ray in diagnosing an acute paranasal
      sinus infection with clinical symptoms. Frontal sinusitis is not an isolated
      disease affecting only the frontal sinuses: Mucosal pathology can also be found
      widely in the ethmoidal cells, and this pathology seems to persist in many cases
      for weeks. MRI showed its capability in confirming these findings. MRI was not
      found to be an over-diagnosing method in registering the secretions and mucosal
      swelling during an acute paranasal sinus infection.

PMID- 8140381
TI  - Effect of surface-active substance on nasal mucociliary clearance time: a
      comparison of saccharin clearance time before and after the use of surface-active
      substance.
AB  - Mucociliary clearance measured by saccharin clearance time is depending on
      ciliary function and on the physiological characteristics of mucus. The aim of
      this study was to determine whether the application of surface-active substances
      changed the mucociliary transport time. Twenty healthy persons were manually
      sprayed with surface-active substance in one of their nose cavities. The
      saccharin clearance time was measured before spraying and statistically compared
      with saccharin clearance time after spraying. Saccharin clearance time was
      significantly shortened immediately after spraying with surface-active
      substances. This difference was not found 2 h later. Our assay indicates that
      surfactant increases the rate of mucociliary transport in the upper respiratory
      tract.

PMID- 8140382
TI  - Effect of vasoconstrictor pre-treatment on obstruction, secretion and sneezing
      after nasal challenge with threshold and suprathreshold allergen doses.
AB  - Acute nasal allergen challenge produces airway obstruction which varies in amount
      and timing with the allergen dose delivered. To see whether different mechanisms
      might contribute variably to mucosal swelling with different amounts of allergen,
      we challenged sensitive volunteers with threshold and 10-times threshold allergen
      doses, with and without topical vasoconstrictor pre-treatment. The
      vasoconstrictor effectively eliminated obstruction at both allergen dose levels,
      suggesting that acute vascular changes were responsible for all the measurable
      obstruction seen with acute allergen provocation. Alpha-adrenergic
      vasoconstrictor pre-treatment was associated with increased weight of secretion
      and numbers of sneezes.

PMID- 8140383
TI  - A multicentre study to assess long-term use of fluticasone propionate aqueous
      nasal spray in comparison with beclomethasone dipropionate aqueous nasal spray in
      the treatment of perennial rhinitis.
AB  - Two hundred and fifty-one patients, aged 16 years and over, with perennial
      rhinitis were recruited to this multicentre, randomized, double-blind, parallel
      group study. One hundred and fifty-nine patients received fluticasone propionate
      (200 micrograms) aqueous nasal spray (FPANS) twice daily, and 83 patients
      received beclomethasone dipropionate (200 micrograms) aqueous nasal spray
      (BDPANS) twice daily; treatment randomization being 2:1, respectively, in order
      to increase the number of patients in the FPANS group as FPANS was the drug under
      study. After 1 year of treatment, nasal blockage (p = 0.002), nasal discharge (p
      = 0.002) and eye watering/irritation (p = 0.048) were significantly improved in
      patients treated with FPANS twice daily, compared to patients treated with BDPANS
      twice daily. The symptom grades for nasal itching (p = 0.052) were improved in
      the FPANS group, but just failed to attain statistical significance at the 5%
      level. The symptom grades for sneezing tended to be better for the FPANS group,
      but the difference was not statistically significant. Assessment of changes in
      the findings during nasal examination (rhinoscopy) and in haematological,
      biochemical and urinary parameters, and measurements of plasma cortisol levels
      during the one year of treatment with the study drugs, showed that there were no
      clinically significant differences between the two treatment groups and that the
      study drugs were equally well tolerated. This study indicates that long-term use
      of FPANS provides better relief than BDPANS for most of the symptoms of perennial
      rhinitis.

PMID- 8140384
TI  - Open septorhinoplasty. Experiences in 200 patients.
AB  - There are two approaches for septorhinoplasty, the endonasal approach and the
      external approach. The external approach is much criticized for the risk of
      columellar skin flap necrosis and visible scar formation. This series of patients
      has shown that the risk can be minimized using a mid-columellar broken incision
      with a meticulous closure technique. The exposure of the surgical anatomy is much
      better than with the endonasal approach, leading to better insight in nasal
      deformities and more detailed reconstruction. There seems to be no reasonable
      objection which can be raised against the columellar incision to reject the open
      approach.

PMID- 8140385
TI  - Staging in rhinosinusitus.

PMID- 8140386
TI  - Giant osteoma of the frontal sinus.
AB  - Osteoma is the most common benign tumour of the nose and paranasal sinuses, and
      the frontal sinus is its most frequent location. This tumour may be discovered
      incidentally on radiographs, or may enlarge to produce symptoms and, rarely,
      complications referable to its location near the orbit and anterior cranial
      vault. A 61-year-old man presented with right proptosis was found to have a giant
      osteoma involving frontal sinus. The aetiology, presenting features, and
      treatment of this tumour are reviewed.

PMID- 8140387
TI  - Efflux of cholesterol from cholesterol loaded macrophages by incubation with
      synthetic HDL-particles.
AB  - Cells from the mouse monocyte/macrophage cell line J774A.1 were incubated with
      acetylated human low density lipoprotein for 2 days, resulting in an
      intracellular accumulation of mainly cholesteryl esters. These in vitro foam cell
      models were used to study the capability of synthetic HDL-particles to promote
      efflux of cholesterol. The synthetic HDL-particles were prepared from recombinant
      human pro-apolipoprotein A-I or human apolipoprotein A-I and phosphatidylcholine.
      Both types of reconstituted complexes were found to have a discoidal structure. A
      24 h incubation of lipid loaded J774A.1 cells with these two types of discoidal
      complexes resulted in an equivalent and marked egress of cholesterol. The effect
      was the same whether the origin of phosphatidylcholine was egg yolk or soybean.

PMID- 8140388
TI  - The effect of daily low-dose iron supplements in female blood donors with
      depleted iron stores: comparison with female non-donors.
AB  - Female blood donors with serum ferritin < or = 20 micrograms l-1 and haemoglobin
      > 120 g l-1 participated in an iron supplement study with two different low-dose
      supplements in a period without donations. Comparable non-donors served as
      controls. Serum ferritin, haemoglobin and transferrin were determined. Increases
      in serum ferritin and in haemoglobin, and decrease in transferrin were highly
      significant (p < 0.01) in both donor groups. In one of the non-donor groups the
      increase in serum ferritin and decrease in transferrin were highly significant (p
      < 0.01), while in the other only transferrin changed significantly (p < 0.03).
      The increases in serum ferritin and haemoglobin over a 5-month period were
      significantly higher among donors (p < 0.001) than among non-donors. We interpret
      the results to mean that the donors have a more efficient iron absorption.

PMID- 8140389
TI  - Thyroid hormones, procollagen III peptide, body composition and basal metabolic
      rate in euthyroid individuals.
AB  - We examined 103 euthyroid men and women within a wide range of body weights and
      ages. Fat free mass (FFM) and body fat (BF) were determined with the total body
      potassium technique, basal metabolic rate (BMR) by indirect calorimetry and serum
      concentrations of thyroid hormones (free and total T3 and T4) and the
      aminoterminal propeptide of collagen III (pIIIp) by immunoassays. BMR was
      positively related to FFM, BF, total T3, the free T3/free T4 ratio and pIIIp, and
      negatively to free T4 (men) and to the ratios free T4/total T4 and free T3/total
      T3. pIIIp was as strongly related to BMR as to total T3. It is suggested that
      pIIIp may serve as an indicator of peripheral energy expenditure. The negative
      relationship between BMR and free T4 was unexpected and different to the
      situation in hypo- and hyperthyreosis where BMR and thyroid hormone are
      positively related. Our hypothesis is that euthyroid subjects with low serum free
      thyroid hormone concentrations and comparatively high BMR may have high
      intracellular thyroid hormone concentrations.

PMID- 8140390
TI  - Morphine and morphine/naloxone modification of glucose, glucagon and insulin
      levels in fasted and fed rats.
AB  - In rats weighing 200-250 g catheters were placed in the internal jugular vein and
      carotid artery. After 1 week of accommodation the training for the experimental
      situation, morphine (10 mg kg-1) was injected intravenously alone or in
      combination with naloxone (0.04 mg ml-1, 0.8 ml h-1). Otherwise no form of
      anaesthesia was used during the experiments. In control fed and fasted rats,
      there were no significant differences in blood glucose. In fed rats, morphine
      increased blood glucose as compared to control rats (p < 0.001). This was not
      seen in the fasted rats. The morphine induced increase in blood glucose in the
      fed rats was abolished by naloxone (p < 0.001). Glucagon was significantly higher
      in fasted than in fed control rats (p < 0.01). It was significantly increased
      after morphine in fed (p < 0.05), but not in fasted rats. The morphine induced
      increase in glucagon in fed rats was abolished by naloxone (p < 0.01). Insulin
      was significantly higher in fed than in fasted control rats (p < 0.05). Morphine
      increased insulin levels significantly in fed and fasted rats (p < 0.001), p <
      0.01). The morphine induced increase in insulin in the fed rats was abolished by
      naloxone treatment. It is concluded that morphine stimulates glucose and glucagon
      release in fed but not fasted rats, and that these increases are caused by opioid
      action. Insulin increases after morphine were proved to be opioid-mediated only
      in the fed state.

PMID- 8140391
TI  - Increased urinary polyamine excretion after starting a very low calorie diet.
AB  - Urinary polyamine excretion has been suggested to reflect hypermetabolism or
      catabolism in different illnesses. In the present study, the excretion of urinary
      polyamines was examined in 12 obese subjects (3 men, 9 women aged 32-55 y, body
      mass index 33.3-64.7 kg m-2) before and during a very low calorie diet (the total
      calorie intake 2100-3350 kJ). In addition, nitrogen balance, basal energy
      expenditure (BEE) and serum thyroid hormone levels were examined. During the
      first week on a very low calorie diet (VLCD) the mean body weight declined from
      121.8 +/- 27.3 to 117.4 +/- 26.2 kg (mean +/- SD, p < 0.001), and after 12 weeks
      of treatment body weight was 106.6 +/- 24.6 kg. Immediate reduction of BEE from
      1.44 +/- 0.24 to 1.34 +/- 0.24 kcal min-1 (p < 0.001) was found within the first
      week of therapy and BEE measured on weight-maintaining diet remained lower at 12
      weeks (1.25 +/- 0.27 kcal min-1, p < 0.01). Serum free T3 decreased and reverse
      T3 increased significantly after starting VLCD. Nitrogen balance remained
      negative during the first 2 weeks on VLCD. A significant increase in total (38%),
      and in N1-acetyl- and N8-acetylspermidine excretions in the urine (40% and 27%,
      respectively, p < 0.05) was found during the first week, but later on the levels
      were not significantly different from the baseline levels.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8140392
TI  - Contributory roles of circulatory glucagon and growth hormone to increased renal
      haemodynamics in type 1 (insulin-dependent) diabetes mellitus.
AB  - The stimulatory effects of growth hormone (GH) and glucagon on renal function are
      well known, but it is uncertain whether these hormones are involved in the
      increase in renal function, characteristic of type 1 (insulin-dependent) diabetes
      mellitus. Therefore, the circulatory levels of GH and glucagon were measured in
      10 type 1 diabetic patients with an elevated glomerular filtration rate (GFR >
      130 ml min-1 1.73 m-2) and in 20 age and sex matched normofiltering patients (GFR
      ranging from 90-130 ml min-1 1.73 m-2). In the patients, fasting glomerular
      filtration rate (GFR) and effective renal plasma flow (ERPF) were determined
      using 125I-iothalamate and 131I-hippuran, respectively, during near
      normoglycaemia. On a separate day, the levels of glucagon and GH were determined
      in the fasting basal state and after exercise. Multiple regression analysis
      disclosed that GFR was positively correlated with HbA1 (r2 = 0.18, p < 0.01),
      glucagon (r2 = 0.14, p < 0.03) as well as exercise-stimulated GH (r2 = 0.10, p <
      0.05). ERPF was independently associated with HbA1 (r2 = 0.24, p < 0.005) and
      glucagon (r2 = 0.18, p < 0.01), whereas renal vascular resistance (RVR) was
      negatively correlated with stimulated GH (r2 = 0.18, p < 0.02). Kidney volume was
      positively correlated with HbA1 (r2 = 0.26, p < 0.001) and inversely with RVR (r2
      = 0.16, p < 0.01), but not with glucagon or stimulated GH. The present study
      suggests that circulatory GH and glucagon play a contributory role in the renal
      haemodynamic changes in type 1 diabetes mellitus.

PMID- 8140393
TI  - Estimated treatment responses in metastatic colorectal carcinoma based on
      longitudinal carcinoembryonic antigen series.
AB  - Patients presenting with advanced or metastatic colorectal carcinoma were
      randomized to treatment with either 5-Fluoro-Uracil + leucovorin or 5-Fluoro
      Uracil + interferon alpha-2-a. Longitudinal series of Carcino-embryonic-antigen
      were obtained and analyzed with a dynamic model in seven of 16 patients had CEA
      levels above 10 ng ml-1. Clinical evaluation based on X-ray, ultrasound and CT
      scans showed a partial response to the given treatment in three of the seven
      patients. The dynamic model consistently estimated the maximal accumulated cell
      kill (approximately three logs) in the patients experiencing a clinical response.
      The remaining four patients with CEA levels above 10 ng ml-1 showed some
      reduction in CEA as a consequence of the treatment cycles, although no clinical
      response could be established. No response was seen among the remaining nine
      patients with CEA levels below 10 ng ml-1.

PMID- 8140394
TI  - Comparison of three independent methods as estimates of platelet inhibition after
      a single dose of acetylsalicylic acid.
AB  - In order to assess the ability of three different (one in vivo, one ex vivo and
      one in vitro) methods to estimate platelet function, 10 healthy volunteers were
      given a single oral dose of 160 mg ASA. Platelet function was assessed before, 4,
      24, 48 and 72 h after dosing by urinary excretion of thromboxane B2,
      filtragometry and collagen-based whole blood aggregometry. Further, in order to
      study mechanisms for platelet aggregation in filtragometry, platelet activation
      was assessed by measurements of beta-thromboglobulin at three different places
      within the filtragometer test unit in another nine healthy subjects. Four hours
      after ASA, the aggregation time during filtragometry increased by 213 +/- 133% (p
      < 0.001) and was parallelled by a decrease in impedance 85 +/- 7% (p < 0.001)
      indicating an inhibition of platelet aggregability in both tests. A subsequent
      gradual recovery was observed with both methods. The excretion of thromboxane B2
      followed the aggregability pattern being maximally reduced by 72 +/- 6% (p <
      0.01) 24 h after ASA and then gradually recovering. All three methods indicated
      that platelet function was still decreased 72 h after dosing. The urinary
      excretion of prostacyclin did not change significantly. The results of
      filtragometry and impedance aggregometry correlated to the logarithm of
      thromboxane B2 excretion (r = 0.60; p < 0.01 and r = 0.49; p < 0.01,
      respectively) and to each other (r = 0.70; p < 0.001). In filtragometry beta
      thromboglobulin increased significantly (p < 0.05) over the filter.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8140395
TI  - Concurrent neutral endopeptidase and ACE inhibition in experimental heart
      failure: renal and hormonal effects.
AB  - Neutral endopeptidase (NEP) inhibitors have been shown to strengthen the effects
      of endogenous atrial natriuretic peptide (ANP). It has been well documented that
      angiotensin I-converting enzyme (ACE) inhibitors act beneficially in chronic
      congestive heart failure (CHF). In the present study, renal and hormonal effects
      of SCH 34826, an orally active NEP inhibitor, were studied in a coronary-ligation
      model of experimental CHF in the rat. The effects were compared to those of
      captopril. The drugs were also administered in combination. In anaesthetized rats
      with CHF, SCH 34826 (90 mg kg-1 sc) elevated plasma ANP from 382 +/- 85 to 658 +/
      120 ng l-1 compared with vehicle (p = 0.002). In sham-operated control rats,
      plasma ANP also increased slightly from 52 +/- 6 to 70 +/- 9 ng l-1 (p = 0.05).
      Plasma renin activity did not change in either group. When given orally for 36 h
      (90 mg kg-1 b.i.d.), SCH 34826 enhanced natriuresis in controls but not in rats
      with CHF. Captopril (0.2 mg ml-1 in drinking water) enhanced natriuresis in CHF
      rats and both natriuresis and kaliuresis in controls. When SCH 34826 and
      captopril were combined, natriuresis was potentiated in control rats as compared
      with captopril alone; in rats with CHF, however, a brisk kaliuresis was seen. The
      excretion of cyclic guanosine monophosphate was enhanced in CHF rats by 52%
      during treatment with SCH 34826 but not with captopril or combination of the two
      drugs. Moreover, captopril suppressed aldosterone excretion both in CHF rats and
      controls when administered alone but not when combined with SCH 34826.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8140396
TI  - Phosphofructokinase activity in human skeletal muscle: effects of euglycaemic
      hyperinsulinaemia and fasting.
AB  - Euglycaemic (approximately 5.5 mmol l-1) hyperinsulinaemic (60 mU [m2]-1 min-1)
      clamps were performed for 2 h after a 10 h and after a 72 h fast on man. Biopsies
      were obtained from the quadriceps femoris muscle before and after each clamp and
      analysed in vitro for phosphofructokinase (PFK) activity under optimal (pH 8.2)
      and regulatory conditions (pH 7.0 and low substrate concentrations). Insulin
      stimulated, and fasting inhibited basal and insulin stimulated muscle glycolysis
      in vivo. However, PFK activity, measured in vitro, was not altered by any of the
      treatments (at pH 8.2: basal [10 h] = 102 +/- 5 mmol kg-1 dry wt min-1, clamp [10
      h] = 104 +/- 6; basal [72 h] = 107 +/- 6, clamp [72 h] = 110 +/- 4 (at pH 7.0:
      basal [10 h] = 10.7 +/- 0.9, clamp [10 h] = 10.7 +/- 1.7; basal [72 h] = 11.7 +/-
      2.4, clamp [72 h] = 9.7 +/- 1.6). Similarly, the activity ratio (7.0/8.2) was
      also not significantly altered by any of the treatments. Euglycaemic
      hyperinsulinaemia did not increase and fasting did not decrease the contents of
      activating hexose phosphates in muscle. The activity ratio increases after
      administration of epinephrine in rabbit muscle and the increase is thought to be
      mediated through a combination of increased hexose phosphates and adenine
      nucleotides (cyclic AMP) (Mansour TE. J Biol Chem 1972; 247: 6059-66). We
      confirmed that 2 h of epinephrine infusion also increased the activity ratio and
      hexose phosphates (but not fructose 2,6-P2) in human muscle.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8140397
TI  - Effect of captopril on the renal veno-arterial gradient of erythropoietin and
      oxygen in unilateral renal artery disease.
AB  - Twenty-nine patients with unilateral renal artery stenosis or occlusion were
      investigated. The veno-arterial gradient (VA-gradient) of erythropoietin (EPO),
      haemoglobin oxygen saturation and plasma renin activity (PRA) was determined
      separately in each kidney before and 1 h after angiotensin converting enzyme
      inhibition (ACE-inhibition). The VA-gradient of EPO and of hemoglobin oxygen
      saturation were the same in the affected and unaffected kidney during basal
      conditions. During ACE-inhibition the VA-gradient of EPO disappeared on the
      affected side but not on the unaffected side. A fall in s-EPO after ACE
      inhibition was demonstrated in the renal vein on the affected side (-1.4 U l-1, p
      < 0.01), in the contralateral vein (-0.8 U l-1, p < 0.01) and in the aorta (-0.6
      U l-1, p < 0.01). The O2-gradients were reduced on both sides after captopril,
      from 10.8-7.5% (p < 0.04) on the affected side and from 10.8-9.0% (p < 0.04) on
      the contralateral. It is suggested that the stimulated renin-angiotensin system
      may be important for EPO production in the affected kidney in unilateral renal
      disease.

PMID- 8140398
TI  - Urinary albumin excretion in a population based sample of 1011 middle aged non
      diabetic subjects. The Copenhagen City Heart Study Group.
AB  - Increased urinary albumin excretion rate (UAER) especially in the range of 20-200
      micrograms min-1, termed microalbuminuria, has been proposed as a risk marker and
      predictor for cardiovascular disease in non-diabetic subjects. Thus it would be
      of importance to describe the distribution of UAER in the non-diabetic
      population. Among 1011 30-70-year-old subjects without diabetes mellitus or
      urinary tract infection, who were invited to participate in a population based
      epidemiological study, the albumin concentration was measured in an overnight
      urine sample. The measurement was performed by an ELISA method. The UAER was
      calculated in units of micrograms min-1 as urinary albumin concentration x urine
      volume/urine collection time. The distribution of UAER was positively skewed with
      a median value of 2.3 micrograms min-1 and a 5-95 interpercentile range of 0-11.0
      micrograms min-1. The UAER held constant with age, but males had higher UAER than
      females, 2.6 (0-13.5) micrograms min-1 vs 2.2 (0-8.3) micrograms min-1; p <
      0.005. The prevalence of microalbuminuria, defined as an UAER in the range of 15
      150 micrograms min-1 in an overnight urine sample, was 3% (95% C.I. interval: 1.9
      4.0). These findings suggest, that the level of UAER which might notify increased
      cardiovascular risk, is lower than in patients with diabetes mellitus, if it is
      considered to be of any clinical relevance.

PMID- 8140399
TI  - Infusion of EPA and DHA lipid emulsions: effects on heart lipids and tolerance to
      ischaemia-reperfusion in the isolated rat heart.
AB  - The aim of the present study was to examine the effect of acute infusion of lipid
      emulsions enriched with either docosahexaenoic acid (DHA) or eicosapentaenoic
      acid (EPA) on heart lipids, tolerance to infusion and to ischaemia-reperfusion.
      Isolated rat hearts were subjected to a 10 min lipid infusion period prior to 25
      min of total global ischaemia and 30 min of reperfusion. Effects on physiology
      and metabolism were recorded during infusion and reperfusion. A more than doubled
      increase of DHA and a 12-fold increase of EPA in terms of relative concentration
      was demonstrated in the free fatty acid fraction after infusion with the
      respective triglyceride emulsions, without any profound change in physiology.
      High levels of DHA were associated with a reduced recovery of left ventricular
      developed pressure (LVDP) and increased release of lactate dehydrogenase (LDH)
      during reperfusion, while the hearts infused with the EPA-emulsion showed a
      recovery comparable to the control group. Heart lipid peroxidation, evaluated by
      release of thiobarbituric acid reactive substances (TBARS) in effluate, was about
      4-fold higher in the DHA-group compared to the EPA-group during start of
      reperfusion and may in part explain the reduced recovery observed in these
      hearts. The present study demonstrates enrichment of DHA and EPA in the free
      fatty acid fraction after a short period of infusion. Protective effects of the
      emulsions were not found, instead the data indicate harmful effects of DHA during
      ischaemia-reperfusion. However, the presence of TBARS in this emulsion could have
      influenced the results.

PMID- 8140400
TI  - Hypouricaemia in a hospital population.
AB  - The prevalence of hypouricaemia in a hospital population was studied.
      Hypouricaemia in females, defined as less than 0.14 mmol l-1 was found in 4.8% of
      all urate requests. Similarly, the prevalence in males, defined as less than 0.20
      mmol l-1 was 6.5%. The largest group displaying hypouricaemia was intensive care
      patients. Oncology patients, particularly those with haematological malignancies
      also exhibited hypouricaemia. Another patient group in which hypouricaemia was
      prevalent were those with diabetes mellitus treated with insulin.

PMID- 8140401
TI  - Sex-reassignment surgery male-to-female. Review, own results and report of a new
      technique using the glans penis as a pseudoclitoris.
AB  - Sexually deviant humans have been mentioned since antiquity and presumably have
      existed at all times. Opinions on the subject have varied throughout recorded
      history. Nowadays we distinguish between different forms of sexual abnormality,
      a.o. transvestites, homosexuals and transsexuals. The estimated prevalence of
      transsexualism varies in different societies and cultures among men between
      1/100.000 and 1/2.900. The etiology of transsexualism is unknown. There have been
      proposed from psychological conditioning in childhood or an unusual paranoic
      state to genetic disturbances. Current investigations indicate that mutations in
      the SRY-gene might be a cause. Surgical sex-reassignment of male transsexuals
      began in the 1930s, but the ideal method has not yet been found. The aim of
      surgical intervention is primarily social and psychologic rehabilitation of the
      patient, as psychiatric therapy invariably fails to "cure" a true transsexual,
      i.e. a person that from early childhood has an absolute and unalterable
      conception of himself as belonging to the opposite sex. In 1978-87 the author
      performed sex-reassignment on 13 transsexual biologic males, using a modified
      technique in which the urethra and glans penis were preserved and the glans
      transposed to a position at the introitus of the neovagina to serve as a
      "pseudoclitoris". In six cases this procedure was successful. The advantage of
      the technique over previous operations is that the glans penis with its sensitive
      mucosa is saved at the neovaginal introitus. The disadvantages are that the glans
      will necrotize if the blood flow through the corpus spongiosum is strangulated
      and that a second-step operation is required to resect and trim the glans after
      it is well healed. Complications and results were similar to those in earlier
      case series. Factors important for success of sex-reassignment operations include
      patient age less than 30 years old at operation and ability of the patient to
      handle a vaginal dilator correctly after the surgical conversion. Orchiectomy
      should be performed as soon as the diagnosis is confirmed, after which the
      estrogen dosage can be reduced.

PMID- 8140402
TI  - [The diagnostic significance of additional electrophysiological studies in
      suspected neurogenic thoracic outlet syndrome].
AB  - The neurogenic thoracic outlet syndrome (TOS) is a controversial clinical entity,
      since unambiguous diagnostic criteria are lacking and abnormal findings are
      absent in many patients. To evaluate electrodiagnostic methods a retrospective
      analysis was done comprising all 75 patients with suspected TOS who had been
      examined electrophysiologically in our laboratory in the last 5 years. 35 of the
      75 patients were finally diagnosed as having TOS, but only 10 of them had a
      corresponding electrophysiological pathology. 6 had "classic" TOS with clinically
      obvious sensorimotor deficits, whereas in 4 the electrophysiologic findings were
      the only abnormalities (in 3 of 4, only minor neurographic anomalies were found).
      Proximal motor stimulation techniques did not improve the diagnostic yield. We
      conclude that electrodiagnostic methods are of little value in the diagnosis of
      TOS if there are no clinical abnormalities. The electrophysiological examinations
      did however reveal distal entrapment neuropathies in 15 of 75 patients (12 carpal
      tunnel syndromes). The frequent detection of such neuropathies in our patients is
      interesting and it justifies per se electrodiagnostic examination of the patient
      with suspected TOS.

PMID- 8140403
TI  - [Edematous benign polyarthritis in elderly persons (RS3PE syndrome). Apropos of
      11 personal cases].
AB  - Edematous benign polyarthritis of the elderly (syndrome of remitting seronegative
      synovitis with pitting edema) affects Caucasians aged over 60, predominantly
      males. The symptoms involve constant edema of the hands and often of the feet,
      with pain and muscular weakness. These symmetric edemas are accompanied by
      arthritis of the extremities and the large joints. The onset of the syndrome is
      acute, ranging from some days to a few weeks, characterized by inflammation but
      no rheumatoid factor. Treatment is similar to that of the classic form of
      rheumatoid arthritis. The evolution, however, is always favorable within a year,
      without subsequent sequelae. The etiology remains undetermined.

PMID- 8140404
TI  - [Fire eater's lung (hydrocarbon pneumonitis)].
AB  - Hydrocarbon pneumonitis is usually related to accidental poisoning in children.
      We describe a case of hydrocarbon pneumonitis after petroleum aspiration in an
      adult fire eater. The main symptoms were cough, dyspnea, chest pain and fever.
      The patient showed bilateral infiltrates in the middle and lower parts of the
      lung, hypoxemia and a restrictive ventilatory defect. The evolution was
      complicated by superinfection with Pseudomonas aeruginosa and by pneumatoceles.
      The acute stage lasted three weeks, and the patient recovered without sequelae
      within two months. Prophylactic application of antibiotics and corticosteroids
      cannot be recommended for prevention of hydrocarbon pneumonitis.

PMID- 8140406
TI  - Easing the edges.

PMID- 8140405
TI  - [Fulminant hepatitis: pathogenesis, clinical aspects and management].
AB  - Fulminant hepatic failure may develop as a complication of liver disease of
      various etiology. Infectious agents, drugs and liver toxins represent the major
      causes of fulminant hepatitis. The function of many organ systems may be impaired
      during acute hepatic failure because of the crucial role of the liver in
      intermediary metabolism. The mortality of 50% or more is mainly due to cerebral
      edema, bleeding from the gastrointestinal tract or disseminated infections. In
      this review the causes, complications and pathophysiology of fulminant hepatitis
      are discussed, with particular reference to the prevention of complications and
      to therapeutic strategies. Moreover, criteria for assessment of prognosis are
      discussed. A case report illustrates the complex clinical picture and frequently
      fatal outcome of the disease.

PMID- 8140407
TI  - Child and elder abuse.

PMID- 8140408
TI  - Venous stasis: successful outcome, and symptomatic relief in patients undergoing
      Linton procedures.
AB  - A retrospective study of forty-one patients who had undergone subfascial ligation
      of perforating veins in the lower extremity, or Linton procedure, is presented.
      All procedures were performed by the same surgeon from 1971 to 1993. Two patients
      underwent bilateral procedures. There were 28 female patients and 13 males.
      Fifteen had a history of smoking. There was a history of previous
      thrombophlebitis in 21 patients, and 21 had a family history of varicosities
      and/or ulceration. Results of venograms and Doppler duplex studies, if done, were
      evaluated. Follow up procedures, such as sclerosing injections and skin grafts,
      were also noted. A total of 25 patients had subsequent sclerosing injections, one
      underwent debridement twice, and one received skin grafts, secondary to
      incisional skin necrosis. It was noted that there was no occurrence of wound
      infection or incisional necrosis when zinc oxide paste boots were applied and
      maintained post-operatively. All patients were contacted directly prior to the
      writing of this article to ascertain prevalence, severity, and circumstances of
      recurrence.

PMID- 8140409
TI  - Neuroleptic malignant syndrome: an overview.
AB  - Neuroleptic Malignant Syndrome (NMS) is a specific, potentially lethal disorder
      related to the usage of dopamine antagonists. The four clinical hallmarks
      associated with this syndrome are 1) hyperthermia, 2) muscle rigidity, 3) mental
      status changes, and 4) autonomic instability. NMS has been estimated to occur in
      0.02% to 3.23% of patients receiving dopamine antagonist therapy. The wide range
      of incidence is probably related to the variability in diagnostic criteria,
      survey techniques, and patient populations. Although the incidence of NMS is
      rare, the inherent mortality for patients developing NMS is significant.
      Fortunately, the mortality has gone from 25% before 1984 to 11.6% thereafter.
      This is probably related to greater awareness of the syndrome by the physician
      with early diagnosis and treatment and also to the advent of newer therapeutic
      modalities. Current methods of treatment include withdrawal of the dopamine
      antagonist, control of the hyperpyrexia, administration of a dopamine agonist,
      and the administration of dantrolene. Electroconvulsive therapy has been
      advocated in patients unresponsive to the above therapies. The reinstitution of
      dopamine antagonist therapy after an episode of NMS is possible. Specific
      protocols are available and are currently under revision by researchers. The
      current data indicate that the risk of a recurrence of NMS is about 30% if the
      protocol is followed.

PMID- 8140410
TI  - Placebo effect.

PMID- 8140411
TI  - Antiepileptic drugs--the drought is over.

PMID- 8140412
TI  - Characterization of type I receptors for transforming growth factor-beta and
      activin.
AB  - Transforming growth factor-beta (TGF-beta) and activin exert their effects by
      binding to heteromeric complexes of type I and type II receptors. The type II
      receptors for TGF-beta and activin are transmembrane serine-threonine kinases; a
      series of related receptors, denoted activin receptor-like kinase (ALK) 1 to 5,
      have recently been identified, and ALK-6 is described here. ALK-5 has been shown
      to be a functional TGF-beta type I receptor. A systematic analysis revealed that
      most ALKs formed heteromeric complexes with the type II receptors for TGF-beta
      and activin after overexpression in COS cells; however, among the six ALKs, only
      ALK-5 was a functional TGF-beta type I receptor for activation of plasminogen
      activator inhibitor-1, and only ALK-2 and ALK-4 bound activin with high affinity.

PMID- 8140413
TI  - Colon cancer screening.

PMID- 8140414
TI  - Model programs take aim at HIV rates in Indonesia.

PMID- 8140415
TI  - Study implicates second-hand smoke.

PMID- 8140416
TI  - New cell transplants may mend a broken heart.

PMID- 8140417
TI  - Chemists get a taste of life at gathering in San Diego.

PMID- 8140418
TI  - 'Lucy,' crucial early human ancestor, finally gets a head.

PMID- 8140419
TI  - Structure of an electron transfer complex: methylamine dehydrogenase, amicyanin,
      and cytochrome c551i.
AB  - The crystal structure of a ternary protein complex has been determined at 2.4
      angstrom resolution. The complex is composed of three electron transfer proteins
      from Paracoccus denitrificans, the quinoprotein methylamine dehydrogenase, the
      blue copper protein amicyanin, and the cytochrome c551i. The central region of
      the c551i is folded similarly to several small bacterial c-type cytochromes;
      there is a 45-residue extension at the amino terminus and a 25-residue extension
      at the carboxyl terminus. The methylamine dehydrogenase-amicyanin interface is
      largely hydrophobic, whereas the amicyanin-cytochrome interface is more polar,
      with several charged groups present on each surface. Analysis of the simplest
      electron transfer pathways between the redox partners points out the importance
      of other factors such as energetics in determining the electron transfer rates.

PMID- 8140420
TI  - Neutrophil activation by monomeric interleukin-8.
AB  - Interleukin-8 (IL-8), a pro-inflammatory protein, has been shown by nuclear
      magnetic resonance (NMR) and x-ray techniques to exist as a homodimer. An IL-8
      analog was chemically synthesized, with the amide nitrogen of leucine-25
      methylated to selectivity block formation of hydrogen bonds between monomers and
      thereby prevent dimerization. This analog was shown to be a monomer, as assessed
      by analytical ultracentrifugation and NMR. Nevertheless, it was equivalent to IL
      8 in assays of neutrophil activation, which indicates that the monomer is a
      functional form of IL-8.

PMID- 8140421
TI  - Requirement of human renal water channel aquaporin-2 for vasopressin-dependent
      concentration of urine.
AB  - Concentration of urine in mammals is regulated by the antidiuretic hormone
      vasopressin. Binding of vasopressin to its V2 receptor leads to the insertion of
      water channels in apical membranes of principal cells in collecting ducts. In
      nephrogenic diabetes insipidus (NDI), the kidney fails to concentrate urine in
      response to vasopressin. A male patient with an autosomal recessive form of NDI
      was found to be a compound heterozygote for two mutations in the gene encoding
      aquaporin-2, a water channel. Functional expression studies in Xenopus oocytes
      revealed that each mutation resulted in nonfunctional water channel proteins.
      Thus, aquaporin-2 is essential for vasopressin-dependent concentration of urine.

PMID- 8140422
TI  - Stat3: a STAT family member activated by tyrosine phosphorylation in response to
      epidermal growth factor and interleukin-6.
AB  - The STAT family of proteins carries out a dual function: signal transduction and
      activation of transcription. A new family member, Stat3, becomes activated
      through phosphorylation on tyrosine as a DNA binding protein in response to
      epidermal growth factor (EGF) and interleukin-6 (IL-6) but not interferon gamma
      (IFN-gamma). It is likely that this phosphoprotein forms homodimers as well as
      heterodimers with the first described member of the STAT family, Stat91 (renamed
      Stat1 alpha), which is activated by the IFNs and EGF. Differential activation of
      different STAT proteins in response to different ligands should help to explain
      specificity in nuclear signaling from the cell surface.

PMID- 8140423
TI  - Formation of nascent intercalated disks between grafted fetal cardiomyocytes and
      host myocardium.
AB  - Fetal cardiomyocytes isolated from transgenic mice carrying a fusion gene of the
      alpha-cardiac myosin heavy chain promoter with a beta-galactosidase reporter were
      examined for their ability to form stable intracardiac grafts. Embryonic day 15
      transgenic cardiomyocytes delivered directly into the myocardium of syngeneic
      hosts formed stable grafts, as identified by nuclear beta-galactosidase activity.
      Grafted cardiomyocytes were observed as long as 2 months after implantation, the
      latest date assayed. Intracardiac graft formation did not induce overtly negative
      effects on the host myocardium and was not associated with chronic immune
      rejection. Electron microscopy revealed the presence of nascent intercalated
      disks connecting the engrafted fetal cardiomyocytes and the host myocardium.
      These results suggest that intracardiac grafting might provide a useful approach
      for myocardial repair, provided that the grafted cells can contribute to
      myocardial function.

PMID- 8140424
TI  - Spatial structure of thrombin as a guide to its multiple sites of interaction.

PMID- 8140425
TI  - Electrostatic properties of thrombin: importance for structural stabilization and
      ligand binding.

PMID- 8140426
TI  - A model for the specificity of fibrinogen cleavage by thrombin.

PMID- 8140427
TI  - Crystallographic determination of thrombin complexes with small synthetic
      inhibitors as a starting point for the receptor-based design of antithrombotics.

PMID- 8140428
TI  - Thrombin interactions with fibrinogen and fibrin.

PMID- 8140429
TI  - Effect of rabbit activated protein C on thrombin generation and fibrinolysis in a
      species-specific in vivo model: effect of modulation of protein S activity.

PMID- 8140430
TI  - Alpha-thrombin receptors and growth signaling.

PMID- 8140431
TI  - Inherited dysfibrinogenemia: emerging abnormal structure associations with
      pathologic and nonpathologic dysfunctions.

PMID- 8140432
TI  - Factor XI activation by thrombin and factor XIa.

PMID- 8140434
TI  - Coagulation abnormalities in patients with precocious coronary artery thrombosis
      and patients failing coronary artery bypass grafting and percutaneous
      transcoronary angioplasty.

PMID- 8140433
TI  - Prothrombin conversion to thrombin by plasminogen activator residing in the
      subendothelial extracellular matrix.

PMID- 8140435
TI  - The pulmonary surfactant protein genes and their regulation in fetal lung.

PMID- 8140436
TI  - Surfactant metabolism.
AB  - Based on these metabolic studies of surfactant lipids in term lambs, in preterm
      lambs not treated with surfactant, and in preterm lambs that have been surfactant
      treated, the following is a synthesis of the overall metabolism of surfactant.
      Preterm surfactant-deficient lungs seem to have all the synthetic and secretory
      pathways for surfactant phosphatidylcholine. Secretory kinetics are slow in
      preterm relative to term animals. Recycling pathways are active in the preterm
      lung, and surfactant used for treatment can be recycled. The major difference
      between the preterm or term lung and the adult lung is that there is almost no
      surfactant phosphatidylcholine catabolism in the developing lung. All assessments
      of surfactant metabolism are complicated by the different forms of surfactant
      within the airspaces that represent different functional surfactant pools. SP-A
      has secretory and reuptake kinetics quite different than those for
      phosphatidylcholine. De novo synthesized SP-A is secreted independently of
      lamellar bodies and may associate with surfactant lipids during the formation of
      tubular myelin. Surfactant treatments do not adversely affect endogenous
      synthetic and secretory phospholipid pathways by feedback inhibition. Therefore,
      surfactant treatments have two primary effects on the preterm lung: physiological
      effects related to surface properties, and metabolic effects resulting from the
      exogenous surfactant phospholipids functioning as substrate for the recycling
      pathways.

PMID- 8140437
TI  - Methods to diagnose fetal lung maturity.

PMID- 8140438
TI  - Epidemiology of acute and chronic lung injury.

PMID- 8140439
TI  - Prenatal corticosteroid therapy to prevent respiratory distress syndrome.
AB  - Recently, an editor observed that the number of clinical trials has multiplied
      and that several trials of the same treatment may be published serially over a
      span of 10 years or more. He was not discussing antenatal CS therapy, was he? He
      added that meta-analysis should decide whether characteristics of patients, their
      therapies, and outcomes in each trial are comparable. Were they? Neither
      controlled trials in large numbers nor meta-analysis of these trials have swayed
      obstetricians toward routine use of antenatal CS as a single intervention.
      Perhaps the data from studies of combined hormonal therapy or of prenatal
      postnatal therapy, or of a combination of both of these approaches will increase
      the use of antenatal CS. Ironically, maybe a retrospective study will provide the
      stimulus. Time will tell.

PMID- 8140440
TI  - Intra-amniotic thyroxine to accelerate fetal maturation.

PMID- 8140441
TI  - Combined hormonal therapy for the prevention of respiratory distress syndrome and
      its consequences.
AB  - In performing this meta-analysis, we have attempted to use comparable data, but
      there are limitations to the information that is available at present. Some
      studies reported results for all patients entered, whereas others reported only
      optimally treated patients (Table 2). Many of the trials have not yet been
      published in final form and subjected to peer review. In addition, all the
      studies reported here were conducted before the widespread use of surfactant
      therapy. It is unclear whether the benefit of antenatal TRH and steroid therapy
      on end points such as death or BPD would persist if surfactant was also used.
      (Surfactant has, however, little impact on the percentage of survivors with BPD,
      perhaps because sicker infants survive with this treatment and go on to develop
      BPD.) Studies comparing antenatal TRH plus steroid plus postnatal surfactant to
      antenatal steroid plus postnatal surfactant are clearly required, and are in
      progress in a number of centers around the world. Because of these limitations,
      the routine use of antenatal TRH plus steroid cannot be currently recommended.
      However, the apparent benefits of this therapy in terms of RDS, death, and CLD
      that have been reported here do suggest that it might be used in selected
      situations. An example is threatened delivery of a very premature infant with an
      immature amniotic fluid pulmonary maturation profile. These infants are at risk
      for RDS and CLD, even if antenatal steroid and postnatal surfactant therapy is
      used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140442
TI  - Synthetic surfactant.
AB  - The mortality reductions after prophylactic and rescue use of synthetic and
      animal surfactants are identical, so the critical issue in surfactant replacement
      is safety, not efficacy. Synthetic surfactant has been shown to reduce both BPD
      and IVH, whereas animal surfactants have not. The reduction in the former may be
      related to synthetic surfactant's more sustained effect on lung function, and the
      reduction in the latter may be due to synthetic surfactant's slower onset of
      action. Synthetic surfactant carries no known antigenic or infectious risks, and
      does not increase the incidence of sepsis. For these reasons, synthetic
      surfactant is a particularly attractive therapeutic option for premature infants
      in need of surfactant replacement.

PMID- 8140443
TI  - Use of natural surfactants to prevent and treat respiratory distress syndrome.

PMID- 8140444
TI  - Perfluorocarbons in the treatment of respiratory distress syndrome.

PMID- 8140445
TI  - Let's think seriously about managed competition.

PMID- 8140446
TI  - The household production of health. Introduction.

PMID- 8140447
TI  - The household production of health: integrating social science perspectives on
      micro-level health determinants.
AB  - Efforts to control disease and improve health in developing countries require
      increasing collaboration between social and medical scientists. This
      collaboration should extend from the early stages of technology development to
      the evaluation and improvement of population-wide interventions. This paper
      provides an integrating framework for social science research on health producing
      processes at the household level, drawing on recent work in economics,
      anthropology, and public health. Further development of theory and methods in
      this area would benefit from interdisciplinary research in categories as defined
      by social and behavioral science in addition to those related to specific
      diseases and intervention programs.

PMID- 8140448
TI  - The developmental niche: a theoretical framework for analyzing the household
      production of health.
AB  - Recent efforts to promote child survival and development internationally have
      focused new attention on the importance of the household as a mediator of both
      environmental risks and programmatic interventions to promote better health. In
      this paper, we introduce a theoretical framework, the 'developmental niche,'
      derived from studies of children's behavior and development in different cultural
      contexts, as a tool for analyzing the household production of health. The
      developmental niche is conceptualized in terms of three basic components: (1) the
      physical and social settings of the child's everyday life; (2) culturally
      regulated customs of child care and child rearing; and (3) the psychology of the
      caretakers. The relevance of each of these components to the household production
      of health is illustrated through examples from research in several cultures,
      including Malaysia, Kenya, Bangladesh, India, and the U.S. Further discussion
      centers on three corollaries of the developmental niche framework that point to
      the interactive relationships among the three components, between the niche and
      the larger environment, and between the niche and the child (or any individual
      seen from a developmental perspective). It is suggested that this approach is
      useful for identifying and collecting relevant information on household-level
      factors that affect health outcomes, and thus for organizing more effective
      interventions. At a theoretical level, the developmental niche framework also
      facilitates understanding processes of mutual adaptation between the individual
      and the environment as they are filtered through the constraints of household
      settings, customs and caretaker psychologies.

PMID- 8140449
TI  - Child care and infectious respiratory disease during the first two years of life
      in a rural Kenyan community.
AB  - Recent research in the U.S. has demonstrated the health risks accompanying the
      increase in use of day care centers for infants and young children, a trend that
      reflects large-scale social and economic changes. The present study reports
      increased risk of respiratory disease in rural Kenyan children, resulting from
      increased exposure to unrelated young children. The shift in risk patterns
      accompanies sociocultural and economic trends during the 1970s: maternal
      participation in work groups for cash cropping and increased school attendance by
      other family members. Thus as in the American case, participation in modern
      patterns of household economics significantly influences the pattern of illness
      for infants and young children.

PMID- 8140450
TI  - Social and psychological costs of preventive child health services in Haiti.
AB  - Much of the research on determinants of health service utilization has focused on
      economic and cognitive variables which influence preventative health behavior.
      Our ethnographic study of maternal perceptions of the barriers and incentives to
      immunization use in Haiti underscores the importance of 'hidden' social and
      psychological costs of utilization, such as embarrassment, fear, child care
      difficulties, and competing demands on maternal time. Findings from focus group
      interviews with mothers, individual interviews with health care providers, and
      observation at health posts identified five categories of maternal factors
      (competing priorities, low motivation, socioeconomic constraints, fears about
      health or social consequences, knowledge and folk beliefs) and five categories of
      system factors (accessibility, acceptability, availability, accommodation,
      affordability) which can deter immunization completion. The discussion focuses on
      how these factors influence maternal decision-making regarding use of preventive
      child health services. More attention is needed on the psychosocial costs of
      health behavior in developing country settings.

PMID- 8140451
TI  - Socio-economic causes and cultural explanations of childhood malnutrition among
      the Chagga of Tanzania.
AB  - This study provides an in-depth analysis of the complexity of factors involved in
      selective child survival among the Chagga people of Mt Kilimanjaro, Tanzania.
      Carried out during the first of a series of post-independence economic crises,
      the study analyzes the impact of fluctuations in world economy, ecological
      stresses, demographic pressures, and class formation in creating conditions of
      poverty and lessening the ability of many Chagga to provide adequate care for
      their children. Qualitative and quantitative information are given from a follow
      up study of families whose children were placed in a nutrition rehabilitation
      program during the drought of 1972-73. Four cases from that study further
      demonstrate the impact of macroeconomic forces on individuals and provide
      material for analyzing a complex pattern of cultural beliefs which made up part
      of the Chagga people's explanations for child malnutrition.

PMID- 8140452
TI  - A causal model of high rates of child mortality.
AB  - The distribution of child mortality has often been misunderstood because of
      insufficient attention to its context. High rates of child mortality in
      developing countries have variously been attributed to child neglect, cultural
      traditions of child care, population pressure, low maternal educational levels,
      lack of medical care, and insufficient basic resources. The model proposed in
      this article organizes factors leading to high child mortality rates onto three
      tiers to contextualize the medical causes of death and the debate over traditions
      of child care. The proximate tier includes the immediate biomedical conditions
      that result in death, typically involving interactions of malnutrition and
      infection. The intermediate tier includes child care practices and other behavior
      that increase the exposure of children to causes of death on the proximate tier.
      The ultimate tier encompasses the broad social, economic, and cultural processes
      and structures that lead to the differential distribution of basic necessities,
      especially food, shelter, and sanitation. The ultimate tier thus forms the
      context of causes located on the other tiers. Research from rural Mexico, Central
      America, and Africa supports various parts of the model, particularly concerning
      traditional parental behavior, which has often been interpreted as child neglect
      but appears in many cases to result ultimately from economic scarcity. Links from
      tier to tier in the model especially warrant further attention from both
      researchers and policy makers.

PMID- 8140453
TI  - Felt versus enacted stigma: a concept revisited. Evidence from a study of people
      with epilepsy in remission.
AB  - Epilepsy is, in the majority of cases, a short-lived and self-limiting clinical
      condition. However, individuals labelled as epileptic frequently continue to feel
      stigmatised, even after their seizures remit. This paper describes the nature and
      extent of stigma in a group of individuals with epilepsy in remission. The
      distinction between 'felt' and 'enacted' stigma is examined, and found to be
      supported by the data.

PMID- 8140454
TI  - Alternative forms of ambulatory care: implications for patients and physicians.
AB  - In recent years, new providers of ambulatory health care have appeared in the
      U.S. These providers are characterized by an emphasis on profit making, where the
      primary care giver, the physician, is often an employee, and where patients
      receive care in a non-traditional setting. Examples of these alternative
      providers include for-profit Health Maintenance Organizations (HMOs),
      freestanding ambulatory care centers (walk-in clinics), and outpatient surgery
      centers. These and other alternative suppliers of health care are of interest
      since they represent a new and growing form of health care delivery. For many
      patients, alternative providers of ambulatory care offer convenient, cost
      effective medical service. However, the emphasis on profit which characterizes
      most of these providers may mean that rural, and inner city areas, as well as the
      poor and uninsured throughout the country, will not be able to take advantage of
      the convenience and savings these providers offer. For physicians, employment in
      an alternative ambulatory care system can be welcome as the costs of starting and
      operating a medical practice soar. Yet, physician-employees often face loss of
      autonomy, status and income. Authors point to the 'proletarianization' of
      physician-employees as they lose control over the location, means and direction
      of their work. This paper explores the development of alternative suppliers of
      health care. It focuses on three providers of alternative ambulatory care and the
      implications of these providers for both patients and physicians. Proposed
      directions for future research include obtaining data on the actual extent of
      alternative providers in the health care market and their effects on consumers
      and the deliverers of medical care.

PMID- 8140455
TI  - Double burden or double blessing? Employment, motherhood and mortality in the
      Longitudinal Study of England and Wales.
AB  - The OPCS Longitudinal Study has been used to follow up women who were married at
      the time of the 1971 census, to see if their employment status and responsibility
      for children at that time had any detectable consequence for their mortality up
      to 1985. Of particular interest was whether the combination of employment and
      child rearing produced any signs of role overload, or its opposite hypothesized
      effect, role enhancement. The results show poorer health among those with neither
      employment nor children, but these effects did not appear to interact. We suspect
      the data reveal health selection as much as health effects of the roles taken
      separately. Whatever the stresses and strains of combining jobs and child
      rearing, they do not appear drastic enough to result in early death.

PMID- 8140456
TI  - A prospective cohort study investigating the explanation of socio-economic
      inequalities in health in The Netherlands.
AB  - In this paper, the objectives, design, data-collection procedures and enrollment
      rates of the Longitudinal Study on Socio-Economic Health Differences (LS-SEHD)
      are described. This study started in 1991, and is the first large-scale
      longitudinal study of the explanation of socio-economic inequalities in health in
      the Netherlands. The LS-SEHD aims at making a quantitative assessment of the
      contribution of different mechanisms and factors to the explanation of socio
      economic inequalities in health. It is based on a research model incorporating
      both 'selection' and 'causation' mechanisms, and a wide range of specific factors
      possibly involved in these mechanisms: health-related life-style factors,
      structural/environmental factors, psychosocial stress-related factors, childhood
      environment, cultural factors, psychological factors, and health in childhood.
      The design of the LS-SEHD is that of a prospective cohort study. An aselect
      sample, stratified by age, degree of urbanization and socio-economic status, for
      approx. 27,000 persons was drawn from the population registers in a region in the
      Southeastern part of The Netherlands. The persons in this sample received a
      postal questionnaire. An aselect subsample of approx. 3500 persons from the
      respondents to the postal questionnaire was, in addition, approached for an oral
      interview. The follow-up of these samples will use routinely collected data
      (mortality by cause of death, hospital admissions by diagnosis, cancer
      incidence), as well as repeated postal questionnaires and oral interviews. The
      response rate to the base-line postal questionnaire was 70.1% (n = 18,973), and
      that to the base-line oral interview was 79.4% (n = 2802). If the LS-SEHD is
      compared to a number of frequently cited longitudinal studies of socio-economic
      inequalities in health from the United Kingdom, it appears that the differences
      with the OPCS Longitudinal Study and the birth cohort studies (such as the
      National Survey of Health and Development) are huge. The LS-SEHD is more akin to
      the Whitehall(I)-study and the West of Scotland 20-07 study. For example it has
      the sample size of the former but the open population and emphasis on social
      factors of the latter. A comparison of the results of various longitudinal
      studies of socio-economic inequalities in health is recommended.

PMID- 8140457
TI  - The conceptualization of meaning in illness.
AB  - The focus of this paper is the development of a conceptualization of meaning
      within the context of serious illness. It is based on a symbolic interactionist
      perspective, with the significance of the concept of meaning for the process of
      adaptation being a primary point of discussion. Meaning, as it is defined here,
      refers to the perceived nature of the relationship between the individual and
      his/her world that is developed within the context of specific events. It is
      comprised of two inextricably linked dimensions: meaning that pertains to one's
      identity and how that is affected by the event of the illness, and meaning which
      pertains to perceived characteristics of the event and to the social
      circumstances that surround it. Interviews with 38 persons living with the stress
      of cancer provide qualitative data that illustrate the concept as it is set forth
      in this paper. Four specific domains relevant to symbolic interactionism were
      explored in these interviews: (1) the individual's response to the illness; (2)
      changes that occurred relative to identify as a consequence of the illness; (3)
      the impact of cancer on the individual's relationship to the social world; (4)
      anticipated effects of the illness on the individual's future. Clinical
      implications of specific aspects of meaning are discussed.

PMID- 8140458
TI  - Epidemiology as an investigative paradigm: the College of General Practitioners
      in the 1950s.
AB  - This paper focuses upon the research investigations of the College of General
      Practitioners in Britain in the 1950s. Beginning with a discussion of Michel
      Foucault's concept of 'pastoral power', the paper proceeds to analyse the ways in
      which the College attempted to set up an epidemiological scrutiny of general
      practices across Britain; from practice by practice observational studies to the
      first National Morbidity Study. The paper concludes by arguing that the
      epidemiological paradigm in general practice was beset by particular internal
      'limits', and was replaced increasingly from the 1960s by an emphasis upon
      psychotherapeutic approaches.

PMID- 8140459
TI  - A new perspective on threatened autonomy in elderly persons: the disempowering
      process.
AB  - This study explored factors other than medical condition and treatments which
      contributed to the discharge experiences of 12 rural and 9 urban patients.
      Interpretive research methodology included document review, observation and in
      depth interviews of all key participants. The purposefully selected sample
      consisted of a total of 21 patients, 22 informal caregivers, and 117
      professionals involved in the hospital and/or home setting. Findings document a
      new perspective on how patients and professionals together contribute to the
      patient's threatened autonomy. Lack of clarity about goals, aspirations, and
      purpose in life and a generally negative frame of mind in the elderly combine
      with professional practice approaches to create a disempowering process. Faced
      with the biomedical orientation and paternalism of professionals, patients with a
      positive mindset and sense of direction and purpose in life did not experience
      threat to their autonomy. The researchers conclude that empowerment strategies
      must encompass a patient-centred approach, which includes an understanding of the
      patient's mindset, goals, aspirations, and sense of purpose within a larger life
      context. This consideration is essential to enable elderly patients to maintain
      autonomy despite continued health care requirements.

PMID- 8140460
TI  - Fears of AIDS in Nigerian students: dimensions of the fear of AIDS Scale (FAIDSS)
      in west Africa.
AB  - A study based on a sample of 2500 individuals aged 18 years and over in six west
      African cities was undertaken for the purpose of determining the cross-cultural
      consistency and replicability of fears about AIDS. A factor analysis of the data
      obtained confirmed a similar factor structure to that reported in Australia.
      Implications for the prevention of HIV transmission in Nigeria and other west
      African countries is discussed. Our findings showed that the fear of AIDS Scale
      (FAIDSS) is a reliable index of fear of aids and is readily scaleable. Other
      implications for health education are considered.

PMID- 8140461
TI  - Association between maternal education and infant diarrhea in different household
      and community environments of Cebu, Philippines.
AB  - Maternal education is one of the strongest determinants of infant survival in
      developing countries, however, questions remain regarding the extent to which its
      effects vary as a function of contextual variables. In this study, a multi-level
      interactive model is used to assess whether the protective effect of maternal
      education on the risk of infant diarrhea is modified by three aspects of the
      mother's familial and community environment: household assets, community economic
      resources and the availability of mothers' clubs. 2484 study participants were
      interviewed in 1984 as part of the Cebu Longitudinal Infant Health and Nutrition
      Study. The findings suggest that the protective effect of maternal education on
      infant diarrhea varies according to the socio-economic environment in which the
      mother lives: maternal education protects against infant diarrhea in the more
      economically and socially advantaged communities but has no effect in the more
      disadvantaged communities. The results also indicate that the protective effect
      of maternal education is smaller in the wealthier households. These data suggest
      that improvement in maternal education level, alone, may not always have the
      expected beneficial effects on infant health. Corollary measures to improve
      access of mothers and children to basic community resources and efforts to help
      mothers be more effective in their various social roles may be necessary
      preconditions for higher levels of maternal education to result in improved
      infant health.

PMID- 8140462
TI  - Mothering on crack cocaine: a grounded theory analysis.
AB  - Mothers who use crack cocaine are commonly believed to be selfish, uncaring, and
      neglectful of their children. For this paper, the grounded theory method was used
      to analyze 68 semi-structured depth interviews with cocaine-using mothers. These
      women's views of motherhood, the strategies they used to manage mothering on
      cocaine, and the contextual influences on mothering outcomes were explored.
      Contrary to popular assumptions, the women highly valued motherhood and held firm
      standards for childrearing. Mothers were concerned about the possible risks to
      their children and used a process of defensive compensation to protect both their
      children and their maternal identities from the negative influences of crack
      cocaine. When unable to fulfil their maternal responsibilities by other means,
      some mothers placed their children with family members, and others lost custody
      involuntarily. When children were forcibly removed, mothers often increased their
      drug use to cope with the loss. Social and economic conditions influenced the
      outcomes of mothering on crack.

PMID- 8140463
TI  - Service attributes and the choice for STD health services in persons seeking a
      medical examination for an STD.
AB  - This article examines choice for STD health services among patients suspecting a
      STD. A total of 825 patients who sought medical treatment at an STD clinic, a
      Family Planning Clinic or a General Practitioner participated in this study.
      Special STD clinics are not well known among patients visiting their GP or a
      Family Planning Clinic. Both perceived unprofessionality and embarrassment were
      reasons for not asking a GP for medical treatment and for not being loyal to
      their GP after a first visit. Most respondents evaluate the 16 service attributes
      as important and/or annoying. Differences in beliefs and evaluations about the
      separate service attributes existed between the three choice behavior groups. The
      results of this study may be useful in making persuasive arguments for the
      existence of special STD clinics, especially when competing for limited
      resources. However, attitudes to service attributes and social norms explained
      only 24% of the variance in scores between the three choice behavior groups. This
      means that other factors (have to) play a role in actual choice behavior. Future
      research should take into account factors, such as: personality traits, perceived
      behavioral control and confidentiality.

PMID- 8140464
TI  - Social stress and state-to-state differences in smoking and smoking related
      mortality in the United States.
AB  - This paper reports on the relationship between the stressfulness of the social
      environment, smoking and mortality rates for malignant neoplasms of the
      respiratory system and chronic obstructive pulmonary disease (COPD). A macro
      social approach was employed with the 50 states of the United States serving as
      the units of analysis. A 'State Stress Index' was computed using stressful events
      in 15 categories (divorce rate, business failures, natural disasters, etc.).
      Smoking behavior was measured by percentage smokers and the average cigarette
      sales per capita. Mortality rates for lung cancer and COPD were standardized by
      age. The percent population living in metropolitan areas, black, below poverty
      line, and with less than high school education were included as controls in the
      multiple regression analysis. The results show that populations that experience
      higher levels of stressful events smoke more heavily and eventually experience
      higher mortality from lung cancer and COPD. These relationships are robust: they
      are replicated for different time periods, for different measures of the
      independent and dependent variables, and with different analytic methods. The
      pattern of findings is consistent with a 'health behavior' model of stress in
      which populations under stress engage in behavior which is extremely inimical to
      health.

PMID- 8140465
TI  - Hot and cold in transformation: is Iban medicine humoral?
AB  - Iban categories of hot and cold are examined in the context of humoral medical
      systems in southeast Asia. These categories are more than binary and
      oppositional: they are also contradictory and can only be understood in terms of
      their capacity for transformation in 'depth'. Analysis of the Iban epistemology
      of temperature sensation reveals the limitations of reductionist empirical
      approaches to hot and cold. Illness is apprehended, at one level, in terms of
      unusual conjunctions of opposite temperatures which signify a deeper disturbance
      in the relationship between body and soul, humans and spirits. Iban therapy
      redefines and relocates these categories in their proper place and at their
      appropriate level. It progresses from hot lay treatments to cool ritual
      treatments, yet cannot be accounted for within a limited framework of homeostatic
      balance. This paper develops an ethnographically grounded definition of
      humoralism which emphasizes non-reductive logic, cultural practice and
      transformation. The key element, transformation, is defined as a transition
      between categories and a shift in the level of interpretation which fundamentally
      alter the Iban experience of body and illness.

PMID- 8140466
TI  - [Various modalities of respiratory assistance].

PMID- 8140467
TI  - [Otorhinolaryngological and digestive complications. Nurses take charge].

PMID- 8140469
TI  - [Nursing care and neuromuscular diseases].

PMID- 8140468
TI  - [Association of Mutual Aid of Polio Patients and Handicapped].

PMID- 8140470
TI  - [Neuromuscular diseases. 35 years of development of medical practices].

PMID- 8140471
TI  - [Myasthenia].

PMID- 8140472
TI  - [Wheelchairs: motility regained].

PMID- 8140473
TI  - [The preparation and administration of anti-neoplastic substances].

PMID- 8140474
TI  - [The nurse in the mines].

PMID- 8140475
TI  - [The 5-nitroimidazoles].

PMID- 8140476
TI  - [Subcutaneous heparin therapy].

PMID- 8140477
TI  - [Diagnosis of coronary and heart valve calcifications using electron beam-CT
      (Ultrafast-CT, Evolution)].

PMID- 8140478
TI  - [Current developments in MRT of the liver: echoplanar imaging].

PMID- 8140479
TI  - [Neural networks--a very promising development for computer-based interpretation
      of radiologic imaging data].

PMID- 8140481
TI  - [Supplements to the calculation of partial tolerance in radiotherapy using the LQ
      model].

PMID- 8140480
TI  - [Defecography and determination of transit time in the diagnosis of anorectal
      dysfunction].

PMID- 8140482
TI  - Ophthalmia neonatorum in a trachoma endemic area.
AB  - BACKGROUND AND OBJECTIVES: Chlamydia trachomatis can be directly transmitted by
      sexual or perinatal contact and indirectly transmitted by flies or fomites.
      Whether distinct epidemiologic forces among human populations or biologic
      characteristics of the organism are responsible for the different routes of
      transmission is uncertain. STUDY DESIGN: To determine if ophthalmia neonatorum
      and trachoma are linked epidemiologically, 38 infants with ophthalmia and 277
      children with trachoma were studied for evidence of C. trachomatis infection
      using culture, antigen and DNA detection tests. The study was performed in a
      trachoma endemic area of central Kenya. RESULTS: Of infants with ophthalmia
      neonatorum, 8% to 9% had microbiologic evidence of ocular C. trachomatis
      infection. Of the children with trachoma, 31% had evidence of chlamydial
      infection. Ninety-two percent of the 59 identified strains causing trachoma
      belonged to the classic trachoma serovars (A, B, Ba and C). Neither of the two
      chlamydial strains recovered from infants with ophthalmia was a trachoma serovar.
      Mothers rarely (3%) had cervical C. trachomatis infection. CONCLUSION: This study
      does not support a major role for perinatally transmitted C. trachomatis
      infection in trachoma epidemiology.

PMID- 8140483
TI  - Development of a polymerase chain reaction assay for the detection of Haemophilus
      ducreyi.
AB  - BACKGROUND AND OBJECTIVES: Haemophilus ducreyi, the causative agent of chancroid
      is a fastidious organism difficult to culture and identify. Consequently, culture
      is an insensitive method for diagnosis. The polymerase chain reaction (PCR)
      offers a sensitive and specific nonculture method for the detection of bacterial
      pathogens. STUDY DESIGN: A polymerase chain reaction (PCR) assay was developed to
      detect the presence of Haemophilus ducreyi. A pair of primers was selected from
      sequences of an anonymous fragment of DNA cloned from H. ducreyi. The primers
      were tested in amplification reactions with both purified DNA and lysed organisms
      for their ability to detect H. ducreyi, and with DNA from a variety of different
      bacteria for their specificity. The utility of the primers for the detection of
      H. ducreyi in samples taken from genital ulcers was also tested and compared with
      culture. RESULTS: PCR was positive for 62% of the specimens that were culture
      positive, however, PCR was also positive for 49% of the culture-negative
      specimens. Comparison of specimens that were dark field positive for T. pallidum
      and PCR-positive with those that were culture-positive for herpes simplex virus
      and PCR positive suggested that PCR was giving true and not random positive
      results. Additional studies demonstrated that the failure of PCR to detect H.
      ducreyi in all of the culture-positive specimens probably resulted from
      inhibitors of the Taq DNA polymerase that were present in the nucleic acids
      extracted from the clinical specimen. CONCLUSION: PCR should be a useful method
      for the detection of H. ducreyi in genital lesions, especially where culture
      sensitivity is poor. However, the presence of unidentified Taq polymerase
      inhibitors in some ulcers specimens require the development of improved methods
      for specimen handling.

PMID- 8140484
TI  - Do bisexual men play a significant role in the heterosexual spread of HIV?
AB  - BACKGROUND AND OBJECTIVES: To assess the potential role of bisexual men in the
      transmission of HIV to women. STUDY DESIGN: The study population consisted of
      homosexual men participating in a longitudinal cohort study on HIV and AIDS in
      Amsterdam, the Netherlands, which started in 1984. Between April and November
      1991, an additional questionnaire was administered concerning sexual behavior
      with both male and female partners in the last 6 months. RESULTS: Of these men,
      27% described their sexual preference as bisexual or heterosexual. In the last 6
      months, 23 (3%) had heterosexual contacts. Vaginal intercourse was the sexual
      technique most practiced. Anal intercourse with a female partner was rare. Four
      heterosexual active HIV positive men always used condoms when having heterosexual
      contact (1 missing). Of the 18 heterosexually active HIV seronegative men, 12 did
      not use condoms consistently with their female partner(s). Two of these 12 men
      also had unprotected insertive anogenital intercourse with male partners, which
      conveys a small transmission risk in the window period in the case of a
      seroconversion. CONCLUSION: Widespread transmission of HIV from these homosexual
      men in this study is not likely. However, the studied men are most probably not
      representative for homosexual men in Amsterdam, the Netherlands. Further study on
      the potential role that bisexual men play in the HIV transmission to women is
      therefore needed.

PMID- 8140485
TI  - Evaluation of the Gen-Probe PACE 2 and the Microtrak enzyme immunoassay for
      diagnosis of Chlamydia trachomatis in urogenital samples.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study was to investigate the value of
      the Gen-Probe PACE 2 assay for routine diagnosis of Chlamydia trachomatis in
      genital specimens of symptomatic and asymptomatic men and women patients. STUDY
      DESIGN: Samples were collected from 90 men and 299 women patients and tested by
      using the Gen-Probe assay and the EIA MicroTrak. Discrepant results were further
      analyzed by immunofluorescence, a second run of the Gen-Probe assay, and a probe
      competition assay (PCA) to establish the number of true positive and negative
      outcomes based on the two tests used. RESULTS: The overall prevalence of C.
      trachomatis was 8.5% in all patients tested (women: 3.7%, men: 13.3%) with an
      overall agreement of 95.4% between the two diagnostic methods. Of the 18
      discordant results, 12 (67%) were considered to be false positive in the Gen
      Probe assay and 3 (16%) false positive in the EIA. Two (11%) positive results
      were missed in the Gen-Probe assay and 1 (6%) in the EIA, all observed in female
      specimens. The sensitivities and specificities of the EIA were 91.7% and 100% for
      men and 100% and 99% for women, and for the Gen-Probe assay were 83.3% and 100%
      for men and 100% and 95.8% for women, respectively, when compared with true
      positive and true negative results. Although the predictive value for all
      positive results (PVP) was 88% for the EIA and 78.2% for the Gen-Probe assay, it
      was only 47.8% for positive female samples when using the Gen-Probe assay.
      CONCLUSION: The Gen-Probe assay revealed a sensitivity comparable with the EIA.
      The accuracy of test results provided by a single Gen-Probe assay was
      considerably lower than by Micro-Trak reducing the utility of PACE 2 as a
      diagnostic technique for Chlamydia diagnosis. Due to the high rate of false
      positive samples in the Gen-Probe assay, positive results with a low value of
      relative light units have to be further analyzed by confirmation procedures.

PMID- 8140486
TI  - Characterization of patients accepting and refusing routine, voluntary HIV
      antibody testing in public sexually transmitted disease clinics.
AB  - BACKGROUND AND OBJECTIVES: To determine the proportion of HIV-infected sexually
      transmitted disease (STD) clinic patients identified during routine, voluntary
      HIV counseling and testing and to characterize patients accepting and refusing
      counseling and testing, we linked data from a blinded HIV seroprevalence survey
      to data from the HIV counseling and testing program. GOAL OF THIS STUDY: This
      study characterizes patients accepting and refusing routine HIV counseling and
      testing in two public STD clinics. STUDY DESIGN: A cross-sectional, blinded HIV
      seroprevalence survey was conducted of 1,232 STD clinic patients offered HIV
      counseling and testing. RESULTS: HIV seroprevalence was higher among patients who
      refused voluntary testing (7.8% versus 3.6%, P = 0.001). Patients who refused
      testing were more likely to report a prior HIV test (45.6% versus 27.2%; P <
      0.001). Among patients reporting a prior HIV test, differences were noted between
      reported prior results, both positive and negative, and blinded results.
      CONCLUSIONS: HIV-infected STD patients may not be detected by routine HIV
      testing, and self-reported HIV results should be confirmed.

PMID- 8140488
TI  - Single dose azithromycin treatment of gonorrhea and infections caused by C.
      trachomatis and U. urealyticum in men.
AB  - BACKGROUND AND OBJECTIVES: Single dose regimens have advantages in the treatment
      of STD. Azithromycin has unique pharmacokinetics that may make single dose
      regimens feasible. Treatment with a single 1 g dose of azithromycin was compared
      to 100 mg doxycycline twice daily for seven days. STUDY DESIGN: This was a
      randomized third-party blinded study on 183 male patients, 176 of whom could be
      evaluated for efficacy. RESULTS: Chlamydia trachomatis was cultured from 148
      patients, 79 receiving azithromycin and 69 receiving doxycycline. Six patients
      receiving azithromycin had positive cultures on follow-up, four were known to
      have had sexual intercourse with infected partners. Fifty-one patients had
      gonorrhea; 28 were treated with azithromycin and 23 with doxycycline. Neisseria
      gonorrhoeae was eradicated from all patients except one receiving azithromycin.
      He denied sexual exposure during follow-up. Sixty patients were infected with
      Ureaplasma urealyticum, 35 were treated with azithromycin and 25 with
      doxycycline. Five patients in each group had positive cultures on follow up.
      Three patients receiving azithromycin and two receiving doxycycline were known to
      have had sexual exposure during follow-up. CONCLUSION: A single dose of
      azithromycin showed similar effectiveness as a 7-day regimen of doxycycline.

PMID- 8140487
TI  - Enzyme immunoassays (EIAs) for the detection of anti-Haemophilus ducreyi serum
      IgA, IgG, and IgM antibodies.
AB  - BACKGROUND AND OBJECTIVES: Chancroid is a risk factor for heterosexually
      acquiring HIV. Controlling its spread may reduce HIV transmission. GOAL OF THE
      STUDY: To develop EIAs for assessing antibody levels and for seroepidemiologic
      studies. STUDY DESIGN: Anti-Haemophilus ducreyi IgA, IgG and IgM EIAs were
      standardized using a crude cocktail antigen. Evaluation was on sera from Kenya,
      Rwanda, Thailand and The Gambia. The two-tailed student's t test was used to
      compare results. RESULTS: The specificity of IgA was 97% (95% confidence interval
      (CI): 95-99%), of IgG was 92% (95% CI: 89-95%), and of IgM was 99% (95% CI: 98
      100%). The sensitivity of IgA was 88% (95% CI: 83-93%), of IgG was 93% (95% CI:89
      97%), and of IgM was 78% (95% CI:71-85%) in patients having an ulceration for
      more than eight days. Thus, 95% (95% CI:92-98%) of the chancroid patients were
      seropositive for at least one antibody type. The IgG and IgA EIAs were more
      sensitive in patients older than 24 years of age. Higher IgG rates were found in
      HIV infected chancroid patients. CONCLUSION: The EIAs should be useful for
      studying the kinetics of antibody levels and the epidemiology of H. ducreyi
      infection.

PMID- 8140489
TI  - Age and clinical immunity to infections with Chlamydia trachomatis.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of chlamydial infection decreases with
      age possibly in part because of increasing immunity. GOAL OF THIS STUDY: To
      determine whether increased age is an independent predictor of decreased
      chlamydial infection and whether chlamydia-specific antibody titer and
      blastogenesis increase with age. STUDY DESIGN: Data from all patients cultured
      for Chlamydia trachomatis between January 1984 and August 1989 were examined and
      multiple logistic regression models were used to identify the independent
      predictors of culture positivity. Antichlamydial antibody titer and chlamydia
      specific blastogenesis were examined for a subset of patients for correlation
      with age. RESULTS: Young age was found to be predictive of chlamydial infection
      independent of all factors examined in men and women. Antibody titers had no
      relation to age (n = 245) whereas the level of blastogenesis correlated only
      weakly with age (n = 155). CONCLUSIONS: Assays of systemic immunity do not
      reflect the protection from chlamydial infection associated with age.

PMID- 8140490
TI  - Relationship between contraceptive method choice and beliefs about HIV and
      pregnancy prevention.
AB  - BACKGROUND AND OBJECTIVES: The goal of this study was to examine the relationship
      between contraceptive method choice and perceptions of HIV and pregnancy risk
      among women at risk of HIV infection and transmission. STUDY DESIGN: Women who
      were infected with HIV or who were at high risk of infection were administered a
      questionnaire assessing sexual and drug-related HIV risk behaviors and beliefs,
      STD and pregnancy history, and intentions, beliefs and behaviors regarding
      pregnancy, childbearing and contraception. RESULTS: Among women who reported
      using a contraceptive method every time they had intercourse, 43% used condoms
      only, 22% used birth control pills only, and 11% used both. Only 58% of
      consistent condom users believed they were very unlikely to become infected with
      HIV in the next year. Controlling for risk factor differences, pill-only users
      were less likely to believe themselves at risk of HIV infection, and more
      confident in their ability to prevent HIV infection, compared with condom-only
      users. CONCLUSION: Results suggest that women's beliefs about the effectiveness
      of a method for pregnancy prevention may generalize to beliefs about the efficacy
      of the method for disease prevention.

PMID- 8140491
TI  - In memoriam. Richard C. Arnold, MD (1906-1992).

PMID- 8140492
TI  - In memoriam. Joseph H. Blount (1926-1993).

PMID- 8140493
TI  - Condom safety and HIV.

PMID- 8140494
TI  - Detection of Chlamydia trachomatis in first catch urine samples from symptomatic
      and asymptomatic males.
AB  - BACKGROUND AND OBJECTIVES: Non-invasive tests are needed to detect Chlamydia
      trachomatis in the genital tract. For men, urine appears to be a useful specimen
      for chlamydial antigen or nucleic acid detection. GOAL OF THIS STUDY: To evaluate
      enzyme immunoassays (EIA) for chlamydial antigens in first catch urine (FCU) from
      symptomatic and asymptomatic men. STUDY DESIGN: We conducted five different
      studies; FCUs and urethral swabs were collected from 1,341 symptomatic and 816
      asymptomatic males. Four EIAs (SureCell, Chlamydiazyme, MicroTrak and IDEIA) were
      tested on the FCU sediments. RESULTS: Prevalence of chlamydia by tissue culture
      isolation was 6% for asymptomatic and 14% for symptomatic men. With symptomatic
      males, the EIA sensitivities and specificities were: SureCell 85% and 97%, IDEIA
      82% and 98%, MicroTrak 86% and 99%, and Chlamydiazyme 91% and 95%. For
      asymptomatic men, Chlamydiazyme sensitivity was 35% with frozen urine vs 77% with
      fresh urine. Overall, tissue culture sensitivity was about 90%. CONCLUSION: EIA
      results on FCU sediments are comparable to that of tissue culture isolation on
      urethral swabs. In many settings, FCU may be the specimen of choice for
      diagnosing chlamydial infections in men.

PMID- 8140495
TI  - [Hemorrhagic complications in patients treated with oral anticoagulants].
AB  - PURPOSE: We have studied the haemorrhagic episodes occurred in patients treated
      with oral anticoagulants, with special reference to their type, frequency and
      severity and analyzing the risk factors that could influence in their production.
      PATIENTS AND METHODS: We carried out a retrospective study in 435 patients of the
      haemorrhagic episodes occurred since January 1989 to December 1991, determining
      in each one the prothrombin time expressed as INR, the time from the beginning of
      treatment, the patient's age and the known or underlying pathologies that could
      predispose to haemorrhage; depending on their severity these episodes were
      classified as moderate and major. RESULTS: We observed 50 haemorrhagic episodes
      in 50 patients (11.5%) which represents 7 x 100 patient/years, 30 (6.8% of the
      total patients or 4.2 x 100 patient-years) were moderate and 20 (4.5% of the
      total patients or 2.8 x 100 patient/years) were major. The mean age in patients
      with haemorrhage was 50.5 years. The incidence of hemorrhages in the first month
      of treatment was 60.8 x 100 patient/years; 9.4 x 100 patient/years in the period
      from the first month to the first year of treatment; and 3.6 x 100 patient/years
      in the period from the first year of treatment. The most frequent type of
      haemorrhage among the moderate ones was haematuria (46%) and among major ones
      digestive haemorrhages (26%). Depending on the coagulation level, 37 patients
      (66%) were within therapeutical range. Depending on patients' sex, the incidence
      was 23 (46%) males and 27 (54%) females. We observed at risk predisposing factors
      hypertension (18%), stroke (12%), hepatic disease (8%) and myocardial infarction
      (8%). CONCLUSION: We have found no relationship between haemorrhagic episodes and
      patients' age or sex. The risk of haemorrhage is higher at the beginning of the
      treatment and increases with the level of anticoagulation, which makes the
      beginning of treatment with lower doses more desirable, increasing them
      progressively until the desired level is achieved. Previous hypertension, stroke,
      hepatic disease and myocardial infarction are factors predisposing to
      haemorrhage.

PMID- 8140496
TI  - [Immunophenotyping study of bone marrow fractions obtained by elutriation in
      allogeneic bone marrow transplantation].
AB  - PURPOSE: Bone marrow transplantation (BMT) is an effective treatment for acute
      and chronic leukaemias. Lymphocyte depletion of donor bone marrow for preventing
      GVHD has been associated with a higher incidence of relapse after allogeneic BMT.
      This association suggests an antileukaemic effect of donor lymphocytes. In vitro
      studies show that cytotoxic T lymphocytes (CD3+ CD56+) and NK cells (CD3-CD56+)
      have an antileukaemic effect. To know which specific subpopulation of lymphocytes
      are depleted by counterflow centrifugation or elutriation, we analysed B, T, NK
      cells and hematopoietic precursors in the marrow fractions after this procedure.
      PATIENTS AND METHODS: Eight patients (6 CML, 1 ALL, 1 B-CLL) received an
      allogeneic BMT with lymphocyte depletion of the bone marrow graft using
      elutriation. After a Percoll gradient, donor marrow mononuclear cells (MNC) were
      separated with this method in five fractions (F1 to F5). RESULTS: Lymphocyte
      depletion of donor marrow was in average of 1.7 log. This depletion was also
      selective, the last fraction containing higher number of cytotoxic T lymphocytes
      and NK cells than the other fractions. Recovery of CD34+ cells in the four
      fractions concerning to post-Percoll marrow was 84%, most of them being in the
      last fraction. CONCLUSIONS: The use of elutriation for lymphocyte depletion is a
      good method for graft manipulation with the feasibility to adjust a
      lymphocyte/Kg. dose. Elutriation may be effective in reducing the incidence and
      severity of graft versus host disease and preserving the antileukaemic effect.

PMID- 8140497
TI  - [Normal values for hematological and hemostatic parameters in the rabbit.
      Determination of new parameters for experimental models of thrombosis and
      hemostasis].
AB  - PURPOSES: Assessment of normal haematological values in the rabbit using a semi
      automatic analyser. Evaluation of new haemostatic parameters necessary for
      experimental models in thrombosis and haemostasis. MATERIAL AND METHODS: 20 New
      Zealand male rabbits of 2-2.5 kg were anaesthetized and blood was collected from
      the jugular vein. The following haematological determinations were carried out
      using a semi-automatic analyser: red blood cells count, haemoglobin, haematocrit,
      indexes, white blood cells count, platelet count and mean platelet volume. The
      parameters used to assess the physiological haemostasis in rabbit were: bleeding
      time, fibrinogen, prothrombin time, activated partial thromboplastin time,
      thrombin time; and others not yet determined in the rabbit: antithrombin III,
      thrombin-antithrombin complexes and F1+2 fragments to measure the basal thrombin
      formation activity, and fibrin D-dimer and fibrinogen degradation products for
      fibrinolysis activity. RESULTS: The haematological results obtained were similar
      than with other techniques, but with no stress influence. Normal values for
      haemostatic parameters studied are shown, including the parameters for the
      determination of physiological thrombin-formation and fibrinolysis activity. F1+2
      fragments and fibrinogen degradation products could not be evaluated.
      CONCLUSIONS: The haematological results obtained were completely normal. All the
      haemostatic parameters studied were found useful to determine the physiological
      activity of coagulation and fibrinolysis in the rabbit, and specially for
      experimental models of hypercoagulability and hyperfibrinolisys states.

PMID- 8140498
TI  - [Multiple myeloma after monoclonal gammopathy of uncertain significance. Study of
      10 patients].
AB  - PURPOSE: To analyse the clinical, biological and evolutive characteristics of 10
      patients with multiple myeloma (MM) previously diagnosed of monoclonal gammopathy
      of uncertain significance (MGUS). PATIENTS AND METHODS: Ten patients with
      diagnostic criteria of MM, included in a series of 114 subjects with MGUS, IgG
      (92 cases), IgA (21 cases) or biclonal IgG+IgA (1 case), diagnosed between 1970
      and 1990, comprise this study group. RESULTS: The actuarial risk of developing MM
      in the series of 114 MGUS was 7.25% (95% CI: 1.5-13) and 16.1% (05% CI: 4.7-27.5)
      at 5 and 10 years of follow-up, respectively. MM occurred suddenly, both on
      clinical and biological grounds, in 8 of the 10 patients. The median period
      between the diagnosis of MGUS and the onset of MM was 48 months (range, 12-153).
      IgG MM appeared in 5 instances and IgA MM in 5 others. Bone pain (7 cases) and
      hypercalcaemic encephalopathy (2 cases) were the commonest clinical
      manifestations. Osteolytic lesions were found in the x-ray scan in 9 patients.
      Eight patients received chemotherapy, objective response being seen in five of
      them. The median survival since the diagnosis of MM was 18 months (range, 0.1
      95). The causes of death in 8 deceased patients include disease progression (4
      cases), pneumonia (3 cases) and neoplasm of the bladder (1 case). CONCLUSIONS:
      This analysis shows the difficulties in predicting the outcome of MGUS, since
      most of the MM seen here occurred abruptly and after a highly variable length of
      time. Thus, patients with MGUS must be followed-up for undetermined time.

PMID- 8140499
TI  - [Role of retinoic acid in the treatment of acute promyelocytic leukemia].

PMID- 8140500
TI  - [Non-Hodgkin's lymphomas associated with human immunodeficiency virus].

PMID- 8140501
TI  - [Acute basophilic leukemia with an intense erythroblastic reaction].
AB  - A patient is presented who had acute basophilic leukaemia with intense
      erythroblastic reaction. The patient, a 66 year-old man, complained of general
      malaise, increased abdominal perimeter and melena. Leucocytosis, as well as
      severe anaemia and thrombocytopenia, were found in his peripheral blood.
      Basophils were present in all maturation stages, along with 7% blast-cells
      showing basophilic stippling, and there were 210 erythroblasts per 100 white
      cells. Erythropoietic hyperplasia (75%) was found in the bone-marrow aspirate,
      without dyserythropoietic signs; the PAS-stain reaction was negative. Of the non
      erythroid cells, 63% were basophils and 34% blast-cells, some of them showing
      basophilic stippling plus metachromasia for tholuidin-blue, positivity for
      omegaexonuclease and negativity for peroxidase stains. The diagnosis of acute
      basophilic leukaemia was confirmed upon demonstration of basophilic stippling in
      the ultrastructural study of the blast-cells. The patient developed acute liver
      failure and renal insufficiency which led him to death. The basis of the
      diagnosis of acute basophilic leukaemia is discussed, as well as the differential
      diagnosis with other conditions presenting with basophilia and the probably
      reactive erythroblastic increase appearing in this case.

PMID- 8140502
TI  - [Initial central nervous system involvement in a case of non-secretory multiple
      myeloma].
AB  - A 56-year old woman with non-secretory multiple myeloma presented with
      involvement of the base of brain and meningeal infiltration. Initial involvement
      of central nervous system is very rare in multiple myeloma, no such pathology
      being reported in non-secretory myeloma thus far.

PMID- 8140503
TI  - [Application of 2 electrophoresis techniques to the analysis of erythrocyte
      membrane proteins in hereditary spherocytosis].
AB  - Seven patients with hereditary spherocytosis have been studied using
      polyacrylamide gel electrophoresis with sodium dodecylsulfate (PAGE-SDS) and
      cytopherometry, in order to obtain information about possible alterations in the
      erythrocyte membrane proteins and in the electrophoretic mobility of whole
      erythrocytes. In four patients, a decrease in Band 4.2 protein was found.
      Histogram plotters proved of interest in showing two subpopulations in two
      patients. In all the cases, the electrophoretic mobility was normal. In two
      patients a spectrin deficiency was found. The study of histograms showed the
      presence of two subpopulations in this group of patients, in which the
      electrophoretic mobility was normal. Finally, one patient showed no deficiencies
      in membrane proteins. This fact can be due to an abnormality of spectrin that we
      could not detect with our techniques.

PMID- 8140504
TI  - [Invasive bronchopulmonary aspergillosis treated with itraconazole in a patient
      with acute leukemia].
AB  - A case of invasive broncopulmonar aspergillosis caused by Aspergillus terreus
      successfully treated with itraconazole is reported in a patient undergoing
      autologous bone marrow transplantation for acute lymphoblastic leukaemia.
      Although the patient was on prophylaxis with fluconazole and she did not respond
      to amphotericin B, there was an excellent response to itraconazole which allowed
      the transplant without any Aspergillus infection during both the transplant and
      the post-transplant periods. Due to its oral administration, good tolerance and
      low toxicity, itraconazole is a promising drug for the treatment of invasive
      broncopulmonar aspergillosis.

PMID- 8140505
TI  - [Acquired factor VIII inhibitor in a patient with rheumatoid arthritis].
AB  - In the present report we describe a 66 year-old-woman, diagnosed of rheumatoid
      arthritis, who suffered a severe haemorrhagic syndrome caused by the presence of
      a circulating inhibitor to factor VIII. Inhibitor quantitation was measured with
      Bethesda test. After treatment with corticosteroids and high-dose immunoglobulin,
      a good clinical response was obtained; factor VIII:C activity increased with the
      disappearance of detectable inhibitor. This response was observed more
      effectively and rapidly than with prednisone treatment alone.

PMID- 8140506
TI  - [Clinical laboratory standardization in the European Community].

PMID- 8140508
TI  - [Hemolytic-uremic syndrome associated with human immunodeficiency virus
      infection].

PMID- 8140507
TI  - [Hemolytic anemia caused by CMV in an immunocompetent patient].

PMID- 8140509
TI  - [Evaluation of the "pink test." Comparison of 2 procedures for the diagnosis of
      hereditary spherocytosis].

PMID- 8140510
TI  - [Importance of anti-N-like antibodies in hemodialysis patients].

PMID- 8140511
TI  - [Erythroid aplasia caused by parvovirus B19 in congenital dyserythropoietic
      anemia].

PMID- 8140512
TI  - [Spanish Club of Hematologic Cytology].

PMID- 8140513
TI  - [Bleeding disorders. Examinations for cancer].

PMID- 8140514
TI  - [Bleeding disorders. Screening for cancer of the uterine cervix].

PMID- 8140515
TI  - [Bleeding disorders. Who will examine and treat?].

PMID- 8140516
TI  - [Bleeding disorders. Endoscopic examination].

PMID- 8140517
TI  - [Bleeding disorders. Treatment possibilities].

PMID- 8140518
TI  - [Bleeding disorders. Removal of the uterus].

PMID- 8140519
TI  - [Bleeding disorders. Hazards of hormone treatment].

PMID- 8140520
TI  - [Bleeding disorders. The cost of screening].

PMID- 8140521
TI  - [When men look into female phenomena].

PMID- 8140522
TI  - [Work environment with a professional nursing perspective].

PMID- 8140523
TI  - [Unemployment Insurance--best to be insured full-time. Interview by Bjarne
      Hansen].

PMID- 8140524
TI  - [Ethics--one doesn't just die of eating pumpernickel].

PMID- 8140525
TI  - [Requirements of occupational health services].

PMID- 8140526
TI  - [Bleeding disorders. Irregularity is the rule].

PMID- 8140527
TI  - [Bleeding disorders. Sickness behavior].

PMID- 8140528
TI  - [Ethics--just priority setting. Interview by Kirsten Bjornsson].

PMID- 8140529
TI  - [Lady with a hat].

PMID- 8140530
TI  - [Euthanasia--mercy killing].

PMID- 8140531
TI  - [Work environment--violence and stress. Interview by Mette Fjordbo].

PMID- 8140533
TI  - [Can we use the ethical guidelines?].

PMID- 8140532
TI  - [Violence--nobody should be alone in the judicial system].

PMID- 8140534
TI  - [Environment--art gives life].

PMID- 8140535
TI  - [Home nursing--access to the medicine cabinet. Interview by Kirsten Bjornsson].

PMID- 8140536
TI  - [Dementia--instead of a nursing home].

PMID- 8140537
TI  - [Basic nursing care--significance of the head-pillow].

PMID- 8140538
TI  - [Ethics. Own responsibility].

PMID- 8140539
TI  - [Change-over--criticism not wanted. Interview by Lars Peter Bergqvist].

PMID- 8140540
TI  - [Professional nursing guidance--to find the lion's energy. Interview by Mette
      Marie Davidsen].

PMID- 8140542
TI  - [Nursing in developing countries--a year in Laos].

PMID- 8140541
TI  - [Executive Board].

PMID- 8140543
TI  - [The beautiful slanting eyes].

PMID- 8140544
TI  - [Euthanasia--we fail. Interview by Mette Mollevang and Jane Kristensen].

PMID- 8140545
TI  - [Euthanasia--patients are the losers. Interview by Mette Mollevang and Jane
      Kristensen].

PMID- 8140546
TI  - [Education--an exciting week].

PMID- 8140547
TI  - What health-system reform means for Texas.

PMID- 8140548
TI  - Vertical integration. Health care's building blocks or a house of cards?

PMID- 8140549
TI  - Battling for a bill. Opposing camps stake their positions in health-system reform
      debate.

PMID- 8140550
TI  - Fear and loathing in R&D. Can Texas biomedical research survive reform?

PMID- 8140551
TI  - Untested waters. Physicians get narrow antitrust safe harbor for negotiating with
      third-party payors.

PMID- 8140552
TI  - Passing stones.

PMID- 8140553
TI  - Acute lymphocytic leukemia in adults: an update.
AB  - The prognosis of adults with acute lymphocytic leukemia has improved over the
      last two decades. With modern intensive chemotherapy regimens similar to those of
      pediatric acute lymphocytic leukemia, the complete response rate is 75% to 85%,
      with a long-term, disease-free survival rate of 20% to 35%. We review the
      clinical, laboratory, and prognostic features of adult acute lymphocytic leukemia
      and discuss the results of therapy.

PMID- 8140554
TI  - [Physiopathological bases of Alzheimer disease].
AB  - Alzheimer's disease is characterized by the presence of two types of brain
      lesions: senile plaques and neurofibrillary degeneration. A peptide named beta A4
      is the major component of the amyloid substance that constitutes senile plaques.
      beta A4 is part of a much larger membrane-associated protein known as the amyloid
      protein precursor (APP) whose gene is on chromosome 21. Mutations on APP gene
      have been linked to several early-onset AD families, demonstrating the
      pathogenicity of APP. The amyloid substance, likely neurotoxic, provokes a
      cascade of biochemical dysfunctions that leads to neurofibrillary degeneration
      (NFD). NFD is characterized by an intraneuronal filamentous accumulation of
      abnormally phosphorylated Tau proteins and is followed by cell death. NFD
      probably first affects the hippocampal region and spreads later to the entire
      isocortex, progressively provoking an intellectual impairment. Together, these
      observations show that experimentally-induced lesions in animal or cell models,
      already at our disposal, will open diagnostic and therapeutical perspectives.

PMID- 8140555
TI  - [French epidemiological bases for the treatment of dementia syndromes and
      cognitive impairment in the elderly].
AB  - Epidemiological studies of Dementia have major methodological problems,
      particularly in France: selection of the studied sample, difficulties for contact
      with elderly people, heterogeneity of place of residence, inaccuracy of the
      diagnostic procedures. In spite of these problems, the Paquid Research program
      allowed to give estimations of prevalence and incidence rate of dementia in the
      French population. On the basis of these results, one can estimate that there are
      actually about 360,000 prevalent cases of dementia in France, of whom 270,000 are
      of Alzheimer type. There were also 150,000 annual-incident cases of dementia.
      However, many of these cases were not considered as demented by the medical
      system because of the absence of cognitive complaints.

PMID- 8140556
TI  - [Dementia. Diagnostic problems].
AB  - NINCDS-ADRDA criteria are currently used to include patients into therapeutic
      trials in Alzheimer's disease (AD). However, specificity of these criteria is not
      very high (from 64 to 87% of diagnosis accuracy). The main causes of errors are
      the other degenerative dementias such as Frontal Lobe Dementias and Diffuse Lewy
      Body Disease. On the other hand, clinical heterogeneity of the patients fitting
      the criteria is large. To increase the power of therapeutic trials it is
      suggested: 1) to use specific criteria to rule out the other degenerative
      dementias when the efficacy of the tested drug is presumed to be specific for AD
      (cholinomimetics, inhibitors of beta-amyloid deposits...); 2) a better definition
      and assessment of the target symptoms when symptomatic improvement is the goal of
      the trial.

PMID- 8140557
TI  - [Critical review of psychometric tests].
AB  - In this paper, a critical review of psychometric tests is proposed. The first
      part describes several aspects of modern, theoretical psychometry and the
      influence of cognitive psychology. The second part focuses on application of
      tests to dementia and preliminary results of a longitudinal study of cognitive
      evolution of patients with mild dementia. Based on this longitudinal study, the
      batteries of tests to be used for diagnosis, or experimental research, or
      clinical trials are described. The authors underline the fact that tests are not
      "good" or "bad" in themselves, and suggest a number of rules for selecting
      inclusion, evaluation and improvement criteria, related to drug treatment.

PMID- 8140558
TI  - [Therapeutic trials in Alzheimer disease. Selection--recruitment and
      stratification].
AB  - Therapeutic trials conducted in Alzheimer's disease have benefited from the
      standardization of diagnostic criteria based on internationally recognized scales
      (DSM III-R, NINCDS-ADRDA) which ensure more valid inclusions. Well specified
      exclusion criteria are also of the utmost importance, in particular depression,
      vascular dementia and concomitant psychotropic drugs. Cognitive and/or functional
      scales allow an appreciation of the severity of the disease. Due to the
      heterogeneity of Alzheimer's disease stratification methods on identified
      prognostic factors i.e. aphasia, extrapyramidal symptoms should be performed.
      Selection of responders during an enrichment phase has still to be discussed.
      Multicentric studies become imperative because of the large number of patients
      required and the difficulties in selecting the adequate patients. These raise the
      issues of investigators' experience, coordination and between center variability.

PMID- 8140559
TI  - [Clinical trials in Alzheimer disease. Methodological problems: what application
      for what indication?].
AB  - For many years, all application dossiers sent to the Ministry of Health for use
      in Alzheimer's disease focused on the correction of cognitive disorders.
      Discussions were centered on the choice of cognitive evaluation scales and
      psychometric tests. The situation has since evolved and in addition to the
      cognitive disorders, applications must also consider daily life activities and
      comportmental disorders. Animal experiences remain classical, the use of aged
      animals not bringing much information and being extremely expensive. Phase I does
      not need to be modified at this stage. Phase II, however, must be done with
      extreme methodological rigor, and especially with an evaluation of pertinent
      clinical benefit in the cognitive and non-cognitive fields. The simple
      statistically significant improvement in one scale or another was not found
      sufficient by the Commission. The pharmaceutical company therefore has to find
      the benefit risk ratio that has real therapeutic interest. If this ratio seems
      pertinent to the Ministry, then phase III studies can be done to confirm longterm
      efficacy on enough patients. The study of drug action is very interesting to
      advance research or even in the application dossier, but in all cases, the ratio
      of pertinent clinical benefit to the risk of side effects remains the cornerstone
      of the decision.

PMID- 8140560
TI  - [Clinical trials in Alzheimer disease. Comments on the project of FDA's
      guidelines].
AB  - The draft guidelines for the clinical evaluation of antidementia drugs give an
      important series of advice on all trials phases: the main objective, in the
      present state of knowledge, is to improve memory. patients must have a confirmed
      dementia, and other causes than Alzheimer diseases must be excluded by
      appropriate investigations. They should not be too severely ill, but they should
      be institutionalized, at least during the first phase of treatment, the placebo
      controlled trial and the dose-effect relationship are necessary, the cross-over
      trial is not advised, the treatment duration should be at least 3 to 6 months,
      two strictly independent evaluations are necessary: cognitive tests, and clinical
      global impression based only on interviews of the patient, the file must contains
      at least 1000 cases with at least 300 cases treated 3-6 months with at least the
      median dose.

PMID- 8140561
TI  - [Pharmacological treatment of ectopic pregnancy].
AB  - The incidence of ectopic pregnancies (EP), has increased significantly in the
      past 20 years. Conservative tubal surgery has long been the treatment of choice.
      However, non-surgical treatment of EP has recently become an alternative to
      surgery. This pharmacological approach uses chiefly methotrexate but attempts
      have been reported using prostaglandins, actinomycin D, potassium chloride,
      mifepristone and anti-hCG monoclonal antibodies. Early diagnosis and close follow
      up of EP by methods including transabdominal and transvaginal ultrasound
      examination and serial measurements of hCG allow to choose the more appropriate
      treatment of EP. The present article gives an overview of the pathophysiology of
      EP, followed by a review of the various pharmacological treatments available.
      This review is centered on methotrexate as the best known drug in this
      indication. Published data on local and general tolerance, efficacy and
      pharmacokinetics are reviewed. A pretherapeutic assessment score using six
      criteria is also discussed, the objective of which is to better define the
      surgical and non-surgical indications. The non-surgical treatment of EP can
      provide a safe and effective alternative to surgical treatment. However, further
      studies are needed to assess the effects of these pharmacological treatments on
      both fertility and risk of recurrence of EP.

PMID- 8140562
TI  - [Monotherapy trial with selegiline in de novo parkinsonian patients] Members of
      the French research group for testing selegiline in early Parkinson disease].
AB  - The French selegiline (S) multicenter trial was conducted in 1990 to test the
      possibility to improve symptomatology of de novo parkinsonian patients (PP)
      during the first three months of treatment by monotherapy S 10 mg/day. A
      randomized double blind placebo, parallel controlled trial was carried out on 93
      patients in 13 neurologic centers. S appears superior to placebo. Global scores
      and motor subscores of UPDRS are improved (p < 0.001, p < 0.01) from the first to
      the third month. Side effects are minor (nausea, dysgueusia, vertigo, lipothymia)
      and hardly different in both groups. S thus appears as inducing a rapid and
      moderate symptomatic effect in de novo PP, during a 3 months long period of
      treatment.

PMID- 8140563
TI  - [The elderly healthy volunteer: a necessity].
AB  - Phase I and II clinical studies performed in healthy elderly volunteers appear as
      a necessity in the design of any drug development. This is particularly true for
      drugs which will be indicated in age-related disorders. The essential aim is to
      obtain a maximum of results on kinetics, dosage and tolerance in this target
      population. Difficulties and specificities of these studies will be developed.
      This issue will contribute to improve the quality of Phase III studies and
      appears as a money-saving strategy.

PMID- 8140564
TI  - [Clinical trials and good clinical practices. Results of a telephone survey in
      Basse-Normandie among 867 physicians].
AB  - In order to evaluate what doctors think about clinical trials in general, 867 of
      them practicing in western Normandy were polled by telephone. The majority of the
      doctors questioned (68.6%) said they were interested in participating in clinical
      trials. Moreover, a number of them (71.7%) had already taken part in such
      studies, most of which were non-comparative studies on drugs already on the
      market. 66.2% of the doctors said they were willing to participate in such trials
      but only 10% of the doctors questioned knew anything about Good Clinical
      Practice. Doctors practicing in this part of France appear to know little or
      nothing about Good Clinical Practice, however, while they are willing to take
      part in clinical research, they are insistant that trials should be of worthwhile
      interest.

PMID- 8140565
TI  - [Diuretics, potassium depletion and ventricular hyperexcitability].
AB  - This prospective randomized study involved 28 patients with moderate essential
      hypertension who for one year, took either hydrochlorothiazide [Esidrex (E) 25-50
      mg per day] or a combination of altizide 15 mg--aldactone 25 mg [Aldactazine (A)
      1 or 2 tablets per day] without potassium supplements. Blood pressure, plasma
      potassium, exchangeable potassium, ventricular premature contractions measured by
      Holter and plasma magnesium were monitored. Blood pressure was brought to normal
      in both treatment groups (p < 0.001). Plasma potassium fell by 0.19 mmol/l with A
      (NS) and 0.35 mmol/l (p < 0.01) with E. Changes in potassium pool were not
      significant. There was a non-significant reduction in the number of ventricular
      premature contractions in both groups. There was no correlation between the few
      cases of frank hypokaliema, fall in potassium pool and complex ventricular
      premature contractions. A review of the literature offers no solid arguments
      suggestive of significant potassium risk associated with these diuretics. Any
      such risk can be eliminated by the use of low doses, combined if necessary with a
      potassium-sparer or a hypotensive agent of another group.

PMID- 8140566
TI  - [Cardiotoxicity of 5-fluorouracil. Clinical picture of 4 cases and a prevention
      proposal].
AB  - 5-fluoro-uracil (5-FU) cardiotoxicity has been often reported during
      chemotherapy. We collect four atypical cases of cardiac side effects in patients
      treated by 5-FU for head and neck tumors. We review the literature about the
      subject, and we propose criteria to detect patients with a high risk level, and
      to prevent this adverse effect incidence.

PMID- 8140567
TI  - [Evaluation of drug side effects over a year in a cardiology service].
AB  - An intensive pharmacovigilance survey was carried out over the course of 1 year
      in cardiology department which revealed 64 reports of adverse drug reactions
      among 61 hospitalised patients, giving an overall incidence of 2.3%. Most of the
      patients in whom adverse drug reactions were recorded were elderly and female.
      The most common adverse events were cardiovascular (72%) and haemorrhagic (9%),
      and related to drugs given for the treatment of cardiovascular disorders. The
      symptoms originating from drug therapy were dominated by sinus arrhythmias (25
      cases), linked to drugs co-administered that have potentially similar cardiac
      pharmacodynamic effects. Seven cases of "torsades de pointe" were also observed.

PMID- 8140568
TI  - [A single-day survey in pharmacies on the consumption of analgesics and
      antipyretics].
AB  - A one day long survey of antalgics and antipyretics consumption was carried out
      in 6 pharmacies of a middle-size city. It first shows the majority of medical
      prescription (62.2%) over self medication (29.4%) and over pharmaceutic advice
      (8.4%) at the drug delivery. Women are the main consumers, especially in the
      youngest ones (20-40 years old). Paracetamol is the most used drug; in this
      indication, the search for the less expensive drug seems usual. Drug abuse cannot
      be demonstrated in this survey; the consumption of this category of drugs appears
      as important although for a short duration; and most of the time for pain
      considered as moderate and trivial. The possibility to carry out such surveys and
      possibly clinical trials in private pharmacies appears as an opportunity.

PMID- 8140569
TI  - [Cough caused by angiotensin converting enzyme. Reflections on the data in
      computerized data banks of the French system of pharmacovigilance].

PMID- 8140570
TI  - [Fatal rifampicin poisoning. Apropos of a case].
AB  - Successful suicide attempts by rifampicin are not commonly reported in
      literature. Fatal cases and mechanisms of death are most of the time unexplained.
      We report a suicidal case in a 33-aged man with fatal course occurring 27 hours
      after acute overdosage with 15 g rifampicin. Criterias of prognostic value are
      discussed: clinical signs in particular the redman syndrome, and biological data.
      None of them allows us to prevent fatal issue but, since cardiac arrest of
      unknown origin may rapidly occur, admission in intensive care must be carried out
      promptly with a total dose absorbed of 12 g and/or evident clinical signs.

PMID- 8140571
TI  - [Guidelines for veterinary use of antibiotics: recommendations of a work group.
      Beleidsgroep Veterinaire Apotheek, Koninklijke Nederlandse Maatschappij voor
      Diergeneeskunde].

PMID- 8140572
TI  - [Project responsible use of veterinary drugs: example of an integrated approach].

PMID- 8140573
TI  - [Once again: what to do with weak animals?].

PMID- 8140574
TI  - [An outbreak of bovine tuberculosis].

PMID- 8140575
TI  - [Echography as part of the management of a swine farm].

PMID- 8140576
TI  - Morphological and functional differentiation of cryopreserved lactating bovine
      mammary cells cultured on floating collagen gels.
AB  - Cryopreserved bovine mammary epithelial cells prepared from lactating mammary
      tissue synthesize and secrete the milk proteins alpha s1-casein, lactoferrin
      (Lf), and alpha-lactalbumin during in vitro culture on collagen gels in serum
      free medium. Each milk protein is differently regulated by detachment and
      thickness of the collagen substratum, fetal calf serum, and prolactin in the
      medium. Collagen detachment did not modulate lactoferrin secretion but strongly
      induced casein secretion, with detachment on day 6 (after formation of cell
      sheets) inducing casein secretion to 3 micrograms/ml medium, which was 2-3-fold
      higher than for cells on collagen detached on day 2 (prior to cell spreading to
      form sheets), and ten-fold higher than for cells grown on collagen not detached.
      Alpha-lactalbumin secretion was also induced, but only to low levels, in cells
      grown on detached but not on attached collagen. Cells grown on thin collagen gels
      secreted lower levels of lactoferrin and casein compared to cells on thick
      collagen. Lactoferrin but not casein secretion was increased in cells grown in
      the presence of fetal calf serum. Casein but not lactoferrin secretion was
      completely dependent on prolactin. Cells grown serum-free on collagen gels
      detached on day 6 of culture showed a polarized epithelial cell layer with high
      differentiation evidenced by the apical microvilli, tight junctions, and fat
      droplets surrounded by casein-containing secretory vesicles. An underlying layer
      of myoepithelial-like cells was also evident. These studies show for
      cryopreserved primary bovine mammary cells prepared from lactating mammary tissue
      the induction of highly differentiated and polarized cell morphology and
      ultrastructure with concomitant induction of the secretion of casein,
      lactoferrin, and alpha-lactalbumin in vitro, and that the non-coordinate
      regulation of milk protein secretion by substratum, prolactin, and serum likely
      involves alternate routing and control of secretion pathways for casein and
      lactoferrin.

PMID- 8140577
TI  - In vitro morpho-functional analysis of pancreatic islets isolated from the
      domestic chicken.
AB  - The technique whereby islets were isolated from the pancreas of chicken and their
      in vitro histological and functional characterization are described in this
      paper. Our isolation procedure consisted of two steps: initially the pancreas
      removed from the chicken was perfused with a 2% solution of collagenase and
      enzymatic digestion was then carried out using the same solution. After this,
      density gradient separation was performed on the digested tissue, by means of
      differing Histopaque solutions: at the end of the separation, the islets were
      studied by light microscopy after treatment with diphenylthiocarbazone, which
      selectively stains beta-cells, and by scanning and transmission electron
      microscopy. The results reported here show the pattern closely resembled that
      encountered when islets were studied in situ. The beta-cells of the islets proved
      in vitro to preserve their functional capability of producing insulin even after
      stimulation with glucose or arginine.

PMID- 8140578
TI  - Role of marginal stress fibers formed in the rat vascular endothelial cells.
AB  - Fluorescence cytochemistry using en face preparations of rat vascular endothelial
      cells (ECs) revealed the localization of actin, fibronectin (FN) and fibronectin
      receptor (FNR) along not only central stress fibers (SFs) but also the cell
      margins. Electron microscopy showed very close proximity between the
      topographical distribution of intracellular microfilament bundles and that of
      subendothelial FN in the EC margins. Therefore, these basal and marginal actin
      cables may be comparable to the well-established central SFs present in ECs.
      Formation of the central SFs was induced in ECs or mesothelial cells in response
      to tension, by which their cellular integrity seems to be effectively maintained.
      However, even when central SF formation was inhibited by cytochalasin D, the ECs
      with marginal SFs showed high resistance to mechanical tension, whereas
      mesenteric mesothelial cells having no such fibers easily lost their integrity.
      Thus, together with central SFs, the marginal SFs characteristic of rat vascular
      ECs may play an essential role in strengthening cell-matrix adhesion.

PMID- 8140580
TI  - Observations of the cellular changes in cultured mouse metrial gland explants and
      of the maintenance of granulated metrial gland cells in vitro.
AB  - Mouse metrial gland explants were cultured for periods of up to 7 days.
      Granulated metrial gland cells migrated from the explants onto the culture dish
      substratum with a peak in numbers of emigrant cells usually found after 1-3 days
      of culture. Histological examination of the cultured explants showed that the
      central core of the explants rapidly degenerated although a viable superficial
      layer of tissue remained throughout the culture period. It is suggested that the
      degenerative changes and the emigration of many granulated metrial gland cells
      from the explants was a result of the large size of the explants used and
      consequential nutrient deprivation. Granulated metrial gland cells were found in
      the viable superficial layer of the explants and on their surface throughout the
      culture period, including day 7 of culture when few granulated metrial gland
      cells remained on the culture dish substratum. The retention of some granulated
      metrial gland cells on the surface of the explants when few remained on the
      culture dish substratum suggests that contact with stromal cells is important for
      the maintenance of granulated metrial gland cells.

PMID- 8140579
TI  - Isolation and characterization of cerebral resistance vessel endothelium in
      culture.
AB  - Organ-derived endothelia have been shown to exhibit distinct patterns of
      morphology and growth responsiveness in vitro. This report describes the
      development, cloning and establishment of long-term serial cultures of rat
      vascular endothelial cells derived from cerebrocortical resistance vessels (small
      arteries and arterioles). Modification of our previous published technique for
      establishing resistance vessel-derived smooth muscle cells (RV-SMC) resulted in
      enhanced levels of endothelial outgrowth from collagenase-treated microvessel
      fragments. Although primary culture growth consisted predominantly of SMC,
      subsequent subcultivation of these cultures revealed the presence of distinct
      endothelial cell clusters within the SMC monolayer. Serial cloning of these
      isolates resulted in a homogeneous population of cells with the characteristic
      endothelial cobblestone growth pattern and positive immunofluorescence for factor
      VIII-related antigen. Previously established RV-SMC frozen stocks provided an
      additional source for obtaining resistance vessel endothelial cells. This was
      made possible by the slow proliferation rate of early-passage RV-SMC and their
      inability to withstand freezing procedures. Endothelial cells from both
      preparations were identical and designated resistance vessel derived endothelial
      cells RV-EC. Upon long-term cultivation (> P15), confluent RV-EC cultures
      expressed spontaneous multicellular cord development that stained positive for
      factor VIII-related antigen. Cell growth studies demonstrated that RV-EC were
      capable of significant growth when maintained in serum-free conditions. Growth
      kinetics using serum-free conditioned medium demonstrated mitogenic activity
      indicating the presence of an autocrine growth factor. Increase growth
      responsiveness was also noted in RV-EC when treated with a variety of peptide
      growth factors. These results indicate that resistance vessel endothelium can be
      successfully isolated and maintained in long-term serial cultures. Furthermore,
      the availability of cultured EC and SMC from this unique microvascular site will
      enable examination of cerebrovascular endothelial-smooth muscle cell interactions
      in vitro and may help to elucidate the mechanisms of altered vascular function in
      disease states.

PMID- 8140581
TI  - Ultrastructural and immunocytochemical characteristics of hepatocytes from
      hepatitis B virus infected chimpanzees.
AB  - Liver tissue samples from four chimpanzees submitted to viral challenge in order
      to test a recombinant anti-hepatitis B virus vaccine, were studied by electron
      microscopy. The vaccinated monkeys showed no evidences of acute viral hepatitis
      (AVH), demonstrating the protection against an infective viral dose; on the
      contrary, the non-vaccinated chimps developed signs of AVH in hepatocytes such
      as: different size and shape, slight dilatation of the rough endoplasmic
      reticulum, disappearance of the mitochondrial crests, broadening of the normal
      space between the membranes of the nuclear coating and presence of laminar bodies
      and cytoplasmic vacuoles. Furthermore, the presence of the hepatitis B virus
      surface (HBV) antigen was confirmed in non-vaccinated monkeys using
      immunocytochemical techniques. Transmission electron microscopy and
      immunocytochemical analysis corroborated the protective effect of the recombinant
      vaccine against the HBV in the vaccinated animals.

PMID- 8140582
TI  - Immunocytochemical localization of a follicle specific protein of the hawkmoth
      Manduca sexta.
AB  - A follicle specific protein (FSP-I) from the hawkmoth Manduca sexta, has been
      localized in developing follicles by immuno-fluorescence and immuno-gold labeling
      techniques. At the light microscopical level, the protein was demonstrated to be
      present in both the basolateral and apical parts of follicular epithelial cells,
      as well as in clearly defined, spherical compartments in the cortex of the
      developing oocyte. Immuno-gold labeling at the electron microscopical level
      revealed the localization of FSP-I in endoplasmic compartments of the follicular
      epithelial cells, in the extracellular matrix of the follicle and in endocytic
      compartments of the oocyte. Our results indicate that M. sexta FSP-I is
      synthetized and secreted by the follicular epithelial cells, after which it is
      taken up by the developing oocyte through endocytic routes.

PMID- 8140583
TI  - The eggshell of Drosophila melanogaster. VIII. Morphogenesis of the wax layer
      during oogenesis.
AB  - Utilizing freeze-fracturing and conventional electron microscopy methods, we have
      studied the details of morphogenesis and construction of the wax layer envelope
      from Oregon R and mutants of Drosophila melanogaster eggs during oogenesis. The
      wax layer is synthesized and secreted by the follicular cells in the form of
      lipid vesicles during stage 10b. During secretion (stages 10b, 11 and 12) the
      lipid vesicles are accumulated on the vitelline membrane surface and become flat.
      At the late stages of choriogenesis (stages 13, 14) the lipid vesicles are
      compressed tightly between the vitelline membrane and the other already
      constructed eggshell layers, so the wax layer becomes very thin and is hardly
      seen in cross-fractured views.

PMID- 8140584
TI  - Topological relationships between porcine anterior pituitary hormones and the
      thioredoxin and glutaredoxin systems.
AB  - Thioredoxin (TRX) and glutaredoxin (GRX) had previously been localized in
      folliculo-stellatae (FS) cells and in only a fraction of glandular cells of the
      anterior pituitary (Padilla et al., 1992). Here we report on a double
      immunolabelling study carried out to determine the correlation between the type
      of secretory cell and the presence of TRX or GRX. TRX and GRX levels were under
      the detection limits in gonadotropes, thyrotropes and corticotropes. A
      considerable proportion of lactotropes contained TRX or GRX; a higher proportion
      of somatotropes contained TRX and all of them were GRX-positive. The secretory
      cell types more frequently detected in the epithelium of well-defined follicles
      lined by TRX-positive FS cells were somatotropes and lactotropes followed by
      corticotropes; gonadotropes and thyrotropes were scarce in these structures.
      Regarding the biological functions of glutaredoxin and thioredoxin, these results
      show that involvement in the processing of secretory proteins is not a general
      property of these two thiol-disulfide oxidoreductases, not even specifically in
      the case of cysteine-rich secretory proteins. On the other hand, another type of
      functional specificity perhaps related to the heterogeneous response of the
      endocrine cells is discussed.

PMID- 8140585
TI  - Thymidine kinase activity in liver and serum of rats after cadmium
      administration.
AB  - Intraperitoneal administration of a cadmium (Cd) salt at concentrations of 2.5
      and 4.0 mg CdCl2/kg of body wt., caused time-dependent severe liver injury, in
      Quinster rats, more intense at the higher administered dose. Thymidine kinase,
      the key enzyme of the salvage pathway of DNA biosynthesis, was strongly affected
      in liver tissue and serum of cadmium-intoxicated rats. Lower thymidine kinase
      activity was observed both in liver and serum of rats treated with the higher
      dose of cadmium, in which the maximal liver injury appeared.

PMID- 8140586
TI  - Rapid plasma clearance of albumin-acrolein adduct in rats.
AB  - Protein adducts are used as markers of chemical exposure. Determination of the
      clearance rate of these adducts from the blood circulation will provide the time
      frame for their measurement. Radioactive albumin was prepared biosynthetically by
      repeated intraperitoneal injections of L-[4,5-3H]lysine to a rat. After an
      affinity purification, an aliquot of this native [3H-lysine]albumin was adducted
      with 5 mM acrolein. Both the native albumin (A-treated group) and the albumin
      acrolein adduct (AAA-treated group) were intravenously injected to separate
      groups of rats, and the clearance of radioactivity from the plasma was measured
      as a function of time. At the end of the experiment (33 h after the injection),
      radioactivity in the whole plasma, and in homogenates of liver, kidney and spleen
      and their trichloroacetic acid(TCA)-soluble and -insoluble fractions in both A-
      and AAA-treated groups, was measured. The results, at the initial 11 h after the
      injection, showed that the radioactivity was cleared from the circulating plasma
      more rapidly in the AAA-treated group (32% of the injected radioactivity
      remained) than the A-treated group (52%). At 33 h after the injection, 22% of the
      injected radioactivity remained in the plasma in the AAA-treated group as
      compared to 32% in the A-treated group. The whole homogenates of liver and kidney
      and their corresponding TCA-soluble fractions showed higher radioactivity in the
      AAA-treated group as compared to the A-treated group. However, the TCA-insoluble
      fractions from livers and kidneys of the AAA-treated group showed lower
      radioactivity as compared to the A-treated group. These results indicated that
      the albumin-acrolein adduct was removed more rapidly from the circulation than
      the native albumin, and degraded more rapidly by the liver and kidney. There was
      no preferential removal or degradation of the adducted albumin by the spleen.

PMID- 8140587
TI  - The cytotoxicity of 50 chemicals from the MEIC study determined by growth
      inhibition of ascites sarcoma BP8 cells: a comparison with acute toxicity data in
      man and rodents.
AB  - In this study, 50 chemicals selected on the basis of existence of particularly
      reliable human toxicity data were screened in a cytotoxicity test involving
      inhibition of the growth of Ascites Sarcoma BP8 cells. These test results are
      part of an international validation program, the Multicenter Evaluation of In
      Vitro Cytotoxicity (MEIC), the aim of which is to recommend batteries of in vitro
      tests to be used for prediction of human toxicity. The cytotoxicities (expressed
      as the concentrations causing 50% inhibition of cell growth) were compared to
      acute toxicity data in humans (LDL0) and rodents (LD50), showing the best
      correlation to rodent data. The results are discussed in relationship to what is
      usually referred to as basal cytotoxic mechanisms as a cause of in vivo toxicity.
      It could be concluded that the predicted results on the basis of mechanistic
      reasoning were not always obtained.

PMID- 8140588
TI  - In vivo inhibition by mipafox of soluble and particulate forms of
      organophosphorus neuropathy target esterase (NTE) in hen sciatic nerve.
AB  - Neuropathy target esterase (NTE) is a protein suggested to be involved in the
      initiation mechanism of organophosphorus-induced delayed neuropathy (OPIDP). We
      previously described two different forms of NTE activity in hen sciatic nerve: a
      particulate form (P-NTE) representing 40-50% of total NTE activity in sciatic
      nerve, and a remaining soluble component (S-NTE). In brain tissue on the other
      hand, more than 90% of NTE activity was recovered as P-NTE. In this work we
      studied the in vivo inhibition of both NTE forms with different doses of mipafox
      and the results were compared with sensitivity to mipafox in vitro. The highest
      dose with no observable neuropathic effects (1.5 mg/kg mipafox p.o.) inhibited
      33% P-NTE and 55% S-NTE activity. The difference between P-NTE and S-NTE activity
      was statistically significant (P < 0.001, n = 9). Higher doses (3 mg/kg) induced
      neuropathy and inhibited NTE more than 75%, but differences between P- and S-NTE
      were not significant (P > 0.5). The greater inhibition of S-NTE than P-NTE in
      vivo contrasts with the observation that S-NTE is less sensitive in vitro.

PMID- 8140589
TI  - Nasal and pulmonary toxicity of glutaraldehyde in mice.
AB  - A concentration-dependent expiratory bradypnea, indicative of sensory irritation,
      occurred during a 15-min oronasal exposure of mice to glutaraldehyde in the
      concentration range of 0.7-4.5 ppm. The level of exposure which led to a 50%
      decrease in the respiratory rate (RD50) was found to be 2.6 ppm. For assessment
      of nasal toxicity, mice were exposed to glutaraldehyde vapours with
      concentrations of 2.6, 1.0, 0.3 ppm for periods of 6 h/day over the course of 4,
      9 and 14 days and were immediately killed. Recovery was studied with another
      group of mice exposed to 1.0 ppm for 14 days and sacrificed after 1, 2 and 4
      weeks rest time. Control groups were concurrently exposed to clean filtered air.
      The earliest lesions were observed in the respiratory epithelium of the septum,
      the naso- and maxilloturbinates, after 4 days of exposure to 0.3 ppm. Severe
      histopathological changes were still observed 2 weeks after the end of the
      exposure to 1.0 ppm. No exposure-related histological abnormalities were detected
      in the trachea and lungs. In conclusion, this experiment demonstrates that
      repeated exposure to 1/10 RD50 is associated with upper respiratory tract damage
      in mice, and this value does not seem to be an acceptable concentration limit for
      occupational exposure.

PMID- 8140590
TI  - Effect of the cephalosporin cefepime on hepatic drug metabolising enzyme activity
      in rats.
AB  - Oral doses of the new cephalosporin cefepime administered to rats for 14 days (40
      mg/kg/day) did not affect the activities of the hepatic drug metabolising enzymes
      measured. By contrast there were highly statistically significant increases in
      all measured parameters in rats treated with phenobarbitone (80 mg/kg/day), the
      positive control. Control activities in male rats exceeded those in females by
      about 2-3 fold.

PMID- 8140591
TI  - Induction of the CYP4A subfamily by perfluorodecanoic acid: the rat and the
      guinea pig as susceptible and non-susceptible species.
AB  - Male Wistar rats and male Duncan Hartley guinea pigs were treated with one i.p.
      dose of perfluorodecanoic acid (PFDA) resulting in pronounced hepatomegaly in the
      rat but not the guinea pig. PFDA treatment also resulted in a 4-fold induction of
      lauric acid 12-hydroxylase activity in the rat but not the guinea pig, indicating
      induction of the CYP4A subfamily of isoenzymes. Consistent with this latter
      conclusion, Western blot analysis of rat liver microsomes using an antibody to
      CYP4A1 and Northern blot analysis of RNA extracts using a CYP4A1 cDNA probe,
      revealed PFDA-dependent induction of the CYP4A subfamily in the rat but not the
      guinea pig. Taken collectively, our data has demonstrated that PFDA, like other
      peroxisome proliferators, is also a CYP4A inducer and conforms to the well
      documented species specificity in induction for this class of compound.

PMID- 8140592
TI  - Correlation between pulmonary cytochrome P450 transcripts and the organ-selective
      pneumotoxicity of 3-methylindole.
AB  - 3-Methylindole (3MI) is a species- and organ-selective pneumotoxin; goats are the
      most susceptible species, mice are intermediate in susceptibility, and rabbits
      are the least susceptible species to its toxicity. Four different cDNA probes
      representative of human cytochrome P450 genes CYP2F1, CYP4B1, CYP2A6, and CYP2B6
      were hybridized against RNA from lung and liver tissues of goat, mouse and
      rabbit. Transcripts representative of pulmonary P450s CYP2F1, CYP4B1 and CYP2B6
      were present in goat lung. Transcripts for the CYP2F1 and CYP4B1 genes were
      observed in rabbit and mouse lung. In general, the probes selectively hybridized
      to pulmonary but not hepatic transcripts of all three species. The differences in
      susceptibilities among the three species could not be explained by the lack of
      4B1 and 2F1 transcripts in the lungs of mice or rabbits that are less susceptible
      than goats, but the selective expression in the lung tissues of all three species
      may participate in the organ-selective bioactivation and pulmonary toxicity of
      3MI in these species.

PMID- 8140593
TI  - N-acetyl cysteine is an early but also a late preventive agent against carbon
      tetrachloride-induced liver necrosis.
AB  - N-Acetyl cysteine (NAC) treatment 30 min before or 6 or 10 h after carbon
      tetrachloride (CCl4) administration significantly prevented the liver necrosis
      produced by the hepatotoxin at 24 h. NAC pretreatment was able to partially
      decrease the covalent binding of CCl4 reactive metabolites at 1 and 3 h of
      poisoning and, to a small extent, the concentration of CCl4 reaching the liver at
      3 h. NAC also diminished partially the CCl4-promoted increases in lipid
      peroxidation at 3 h, but had an enhancing effect of its own of small intensity.
      Results suggest that early and late protective effects of NAC might be
      attributable to its prior conversion to cysteine and glutathione.

PMID- 8140594
TI  - Effects of pentachlorophenol (PCP) on the pituitary and thyroidal hormone
      regulation in the rat.
AB  - Investigations on rats after repeated application of pentachlorophenol (PCP)
      should clarify whether thyroid side effects caused by this xenobiotic can be seen
      in a dose range which does not cause major toxic effects. Female rats of the
      Wistar strain were treated with 3 and 30 mg PCP/kg body wt. daily by gavage for
      28 days. To assess the potential impact of impurities the study was performed
      both with pure and technical grade PCP at the dosage of 3 mg.kg-1.day-1, and at a
      level of 30 mg.kg-1.day-1 with pure PCP only. The effects in animals on normal
      iodine diet were compared to those in animals on a low iodine diet. No decrease
      of body wt. was noticed, only the liver weights were increased slightly in
      animals treated with 30 mg.kg-1.day-1 PCP. However distinct effects on thyroid
      hormones as well as on thyrotropin (TSH) were observed: a pronounced fall of
      circulating thyroxine (T4) and triiodothyronine (T3) levels was accompanied by
      lower levels of both free thyroid hormones and TSH, and the T4:T3 ratio was
      decreased in serum. Furthermore the intrathyroidal hormone stores were reduced.
      An interference of PCP at pituitary or hypothalamic level is assumed as a major
      mode of action. Additional effects of the test substance on peripheral conversion
      can be suspected.

PMID- 8140595
TI  - The effect of dithiothreitol on the activity of tityustoxin from the scorpion
      Tityus serrulatus venom.
AB  - The acetylcholine (ACh) liberating effect on rat brain slices of tityustoxin, an
      alpha toxin from the scorpion Tityus serrulatus venom, was measured in the
      absence and presence of dithiothreitol (DTT). The rate of net ACh liberation by
      toxin concentrations of 2 nmol in 5 ml of organ bath, was 7.5 +/- 0.09 nmol g-1
      min-1. If DTT at a final concentration of 1 mM was added after a 10-min
      incubation period with toxin alone, inhibition of tityustoxin activity was 94%.
      With DTT 0.1 or 0.01 mmolar inhibition was 74% and 57%, respectively. The intense
      secretagogue effect, both in salivary and pancreatic glands of adult rats,
      induced by sublethal doses of tityustoxin was not affected by i.v. injection 10
      min later of DTT 1 mumol g-1 of rat weight. When tityustoxin was injected i.p. at
      a dose 3 times the LD50 in mice, death ensued in 40 to 60 min. If toxin
      inoculation in mice was followed 10 min later by DTT 1 mumol g-1 of mouse weight,
      injected i.p. or i.v., deaths were delayed to 90 to 110 min, but no survival was
      observed. At necropsy, none of the mice treated with DTT showed any signs of
      pulmonary edema.

PMID- 8140596
TI  - Measurement of urinary androgen sulfates without previous hydrolysis: a tool to
      investigate adrenarche. Validation of a commercial radioimmunoassay for
      dehydroepiandrosterone sulfate.
AB  - A commercial 125I radioimmunoassay designed for the quantification of
      dehydroepiandrosterone sulfate (DHEAS) in blood samples was tested for its direct
      applicability to 24-hour urine samples from children and adults. Average
      recoveries in parallelism and spiking experiments were found to be near 100%.
      Intra- and inter-assay coefficients of variation were below 10%. Urinary DHEAS
      concentrations determined directly by the radioimmunoassay (x) differed only
      slightly from corresponding radioimmunoassay values (y) obtained after C18
      reversed-phase extraction and LH-20 chromatography (y = 0.85x + 0.12; r = 0.99).
      Cross-reactivity data from related steroids suggested only a small contribution
      to the DHEAS titer by other steroids. In 8-year-old children compared to
      preadrenarchal children (4 years old) a clearly increased median daily urinary
      DHEAS output could be observed both for absolute excretion data (0.163 versus
      0.05 mumol/d, P < 0.01) and for excretion values related to body surface area
      (0.181 versus 0.071 mumol/d/1.73 m2, P < 0.05). However, this "onset of
      adrenarche" was no longer statistically significant when urinary creatinine was
      taken as adjustment parameter for renal androgen sulfate output. After correction
      with the individual body surface area, rises of urinary DHEAS from childhood to
      adulthood were nearly in the order of the literature data on age-corresponding
      serum increases of DHEAS. In conclusion, the direct radioimmunological
      quantification of DHEAS in 24-hour urine samples with subsequent correction for
      individual body surface area appears to present a physiologically meaningful way
      to assess the adrenal gland's secretory activity for this androgen sulfate.

PMID- 8140597
TI  - Measurement of urinary androgen sulfates without previous hydrolysis: a tool to
      investigate adrenarche. Determination of total 17-ketosteroid sulfates.
AB  - According to published data the group of urinary total 17-ketosteroid sulfates
      appears to represent an index of overall adrenal androgen production, at least
      before the onset of puberty. To quantify total 17-ketosteroid sulfates a modified
      colorimetric assay based on the Zimmermann reaction was validated. 17-ketosteroid
      sulfates were measured without previous hydrolysis (as conjugated Zimmermann
      chromogens against authentic dehydroepiandrosterone sulfate (DHEAS) as assay
      standard) after C18 reversed-phase extraction and LH-20 chromatography. Intra-
      and inter-assay coefficients of variation were 8.4% (15.0%) and 5.9% (17.6%),
      respectively, at urinary 17-ketosteroid sulfate concentrations of 10.8 (1.9)
      nmol/ml. Recoveries observed in spiking and parallelism experiments varied
      between 88 and 102%. In a group of 4-year-old children showing a renal DHEAS
      output of less than 0.1 mumol/d/1.73 m2 (measured by radioimmunoassay) a
      relatively high median 17-ketosteroid sulfate excretion of 1.29 mumol/d/1.73 m2
      was found. Older children aged 8 years as well as a group aged 12-14 years
      demonstrated only moderately higher urinary 17-ketosteroid sulfates whereas
      excretion of DHEAS/d/1.73 m2 more than tripled from age group to age group. For
      children from 8 years onwards, adolescents, and adults, linear regression
      analysis indicated that urinary DHEAS elevations seem to contribute with a
      constant proportion of approximately 70% to the increments of total urinary 17
      ketosteroid sulfates. These findings suggest that the attainment of such a
      constant relationship (between the total 17-ketosteroid sulfates and their major
      component) from about 8 years of age onwards could represent the hormonal
      correlate of the completion of the continuous zona reticularis in the adrenal
      gland (developing around this age from a focal reticularis zone).

PMID- 8140598
TI  - Synthesis of a fluorescent steroid derivative with high affinities for the
      glucocorticoid and progesterone receptors.
AB  - The synthesis of RU 45196, an 11 beta-substituted 19-norsteroid of the estra-4,9
      diene series, incorporating the nitrobenzoxadiazole (NBD) fluorophore, is
      reported. The highly fluorescent target compound displayed remarkable affinity
      for both the progesterone and glucocorticoid receptors. The present work
      demonstrates for the first time that it is indeed possible to design fluorescent
      steroid conjugates which maintain very high affinities for their cognate
      receptors and which are potentially useful for mechanistic and diagnostic
      purposes.

PMID- 8140599
TI  - N-alkylation of 17-azasteroids.
AB  - N-Alkylation of 17-azasteroid lactams (16-oxo-17-azaandrost-5-en-3 beta-ol
      acetate 3 and its D-homo analog 4) was studied. It has been found that both
      lactams are readily alkylated with iodomethane or iodoethane. In contrast to this
      there was no reaction with 2-iodo-6-methylheptane due to the steric hindrance.
      1,4-Addition of lactam to the conjugated systems was also studied. The addition
      to acrylonitrile proved to be easy compared to crotononitrile. However the
      efficient addition to the latter compound was also attained by using potassium t
      butoxide as a base in t-butanol.

PMID- 8140600
TI  - The synthesis of 7 alpha-methyl-substituted estrogens labeled with fluorine-18:
      potential breast tumor imaging agents.
AB  - The 7 alpha-methyl substituent is reported to increase the binding affinity of
      estradiol for the estrogen receptor (ER). In order to evaluate whether this
      substituent would improve the in vitro binding characteristics and the in vivo
      tissue distribution of 18F labeled estrogens that we are developing as positron
      emission tomographic (PET) imaging agents for ER-positive breast tumors, we have
      prepared four 18F labeled analogs of 7 alpha-methylestradiol. These ligands were
      labeled in the 16 alpha or 16 beta position with 18F by nucleophilic displacement
      of the corresponding epimeric estrone trifluoromethanesulfonates with 18F
      fluoride ion. Lithium aluminum hydride reduction afforded the estradiol (E2)
      series, while lithium trimethylsilylacetylide addition provided the 17 alpha
      ethynylestradiol (EE2) series. The decay-corrected yields were 2-35% for a
      synthesis time of 85 minutes for the E2 series, and 120 minutes for the EE2
      series, and the effective specific activities were 158-1213 Ci/mmol. In nearly
      every case, the 7 alpha-methyl substituent increases ER binding affinity
      (measured at 25 C) and decreases binding to high affinity serum steroid binding
      proteins, alphafetoprotein, and sex steroid binding protein; this substituent,
      however, increases the lipophilicity and the predicted non-specific binding
      (estimated from octanol-water partition coefficients determined by reverse-phase
      high-pressure liquid chromatography/[HPLC]), with the result that the ratio of ER
      binding to non-specific binding is nearly the same for the 7 alpha-methyl
      substituted analogs as for the corresponding unsubstituted analogs. In vivo
      distribution studies demonstrated a high level of receptor-mediated uptake in
      receptor-rich target tissues (uterus, ovaries), and in some cases, other tissues
      with low ER titers (secondary target tissues, e.g., muscle, thymus) showed
      significant displaceable uptake, presumed to be receptor-mediated.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8140601
TI  - Heat shock protein induction blocks hormone-sensitive steroidogenesis in rat
      luteal cells.
AB  - A variety of agents induce heat shock proteins (HSPs) in addition to heat shock.
      The heat shock response and its effects on luteal function have not been
      investigated, but provocatively, many of the agents known to induce HSPs impair
      progesterone synthesis in luteal cells. We therefore investigated whether HSP
      induction might influence luteal function. Rat luteal cells exposed to a commonly
      used heat shock paradigm (45 degrees C; 10 min) were shown to induce HSP of 70
      kDa (HSP-70). Heat shock also caused a complete abrogation of LH-sensitive
      progesterone and 20 alpha-dihydroprogesterone secretion, and blocked
      steroidogenesis in response to 8-bromo-cAMP and forskolin. In contrast, heat
      shock had no effect on cAMP accumulation in response to LH or forskolin, or on
      basal progestin secretion. Heat shock inhibition of steroidogenesis was fully
      reversed by 22R-hydroxycholesterol (22-OH cholesterol), a cell- and mitochondria
      permeant cholesterol analog. Inhibition of transcription with actinomycin D
      blocked HSP-70 induction and significantly reversed the inhibition of
      steroidogenesis by heat shock treatment. The antisteroidogenic response of heat
      shock was coincident with induction of HPSs and both events were transcription
      dependent. These findings provide strong evidence that HSP induction inhibits
      steroidogenesis. The mechanism of the antisteroidogenic action of HSP induction
      appears to be due to interference with translocation of cholesterol to
      mitochondrial cytochrome P450scc, a conclusion based on reversal of inhibition by
      22-OH cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140602
TI  - In vivo effect of free fatty acids on the specific binding of
      glucocorticosteroids to corticosteroid binding globulin and liver receptors in
      immature rats.
AB  - Stimulating lipase activity with heparin (200 IU/kg b.w.) increased the plasma
      free fatty acid (FFA) concentration of immature rats (15 days). The effect of
      this elevated FFA concentration on glucocorticoid binding to corticosteroid
      binding globulin (CBG), and liver cytosol glucocorticoid receptor (GR), was
      analyzed. The plasma FFA concentration increased 2-fold, 10 minutes (P < 0.001),
      20 minutes (P < 0.01), and 60 minutes (P < 0.01) post-heparin. The corticosterone
      (B) and progesterone concentrations were unchanged 60 minutes post-injection. The
      binding activity of immature rat CBG for B dropped 50% (P < 0.001) 60 minutes
      post-heparin injection, decreased B binding and increased plasma FFA were
      correlated (r = -0.8). The decreased B binding resulted from a 2-fold decrease in
      the apparent number of CBG binding sites; the affinity constant (Ka) remained
      unchanged. The liver cytosol endogenous FFA content of immature rats was also
      increased 2-fold, 60 minutes after heparin-induced lipolysis. The increased
      cytosol FFA, with no significant change in glucocorticoid, was accompanied by a
      significant decrease in dexamethasone binding to liver cytosol glucocorticoid
      receptor. The decrease resulted from a significantly lower apparent Ka for
      dexamethasone and fewer receptor binding sites (n). There was a good inverse
      correlation between Ka (r = -0.93) and n (r = -0.90) and the increased liver
      cytosol FFA content. Thus the higher plasma FFA induced in vivo by lipase
      activation or a standard FFA mixture probably causes conformational changes in
      CBG and GR, reducing glucocorticoid binding to immature rat CBG and liver GR.

PMID- 8140603
TI  - Short report on the 5th Symposium on the Analysis of Steroids.

PMID- 8140604
TI  - Early oral contraceptive history: norethynodrel is not a prohormone.

PMID- 8140605
TI  - Ethics and the pediatric perioperative nurse (continuing education credit).
AB  - 1. Nurses encounter a number of ethical issues specific to the pediatric patient;
      however, they participate in surgical procedures that are the result of decisions
      made elsewhere, and in which they have little or no input. Nurses may believe
      that decisions are based on the best interest of the decision makers, and not the
      best interest of the patient. 2. Ethical problems often occur when one asks
      oneself the question, "What should I do?" Ethical problems exist when available
      facts and information do not make it clear what must be done and uncertainty
      prevails about which action to choose. 3. By using a rational approach to the
      resolution of ethical dilemmas, decisions based on emotions and incomplete
      information can be avoided. The nurse must identify these issues, act on them,
      and evaluate results. The evaluation of actions will assist nurses in developing
      an understanding of ethical decision making and its application to practice
      issues on a regular basis.

PMID- 8140606
TI  - A quality improvement approach to latex precautions.
AB  - 1. When Arkansas Children's Hospital (ACH) updated its latex precautions, the
      staff used a nine-step process: find a process to improve; organize a team that
      knows the process; clarify current knowledge of the process; understand the
      causes of process variation; select the process improvement; plan the improvement
      and continue data collection; do the improvement, data collection, and analysis;
      check and study results; and act to hold gains and to continue to improve the
      process. 2. It is our responsibility as nurses to safeguard patients who are at
      high risk for latex allergy. Our vision at ACH is to simplify nursing care for
      the latex sensitive patient. This is achieved by implementation of hospital
      policy and departmental protocols, improvement of communication, education of
      staff members and patients/families, and commitment from all hospital employees
      to quality patient care. 3. Updating hospital policy and protocols regarding
      latex sensitivity is an important but challenging task. Use of the quality
      improvement process facilitates and expedites change.

PMID- 8140607
TI  - Clubfoot: nature and treatment.
AB  - 1. Clubfoot is a relatively common abnormality that occurs in 1 per 1,000 live
      births. Untreated, clubfoot precludes normal gait because the patient is forced
      to walk on the lateral side of the forefoot. 2. Treatment of clubfoot should
      begin at birth to avoid a fixed and disabling deformity. Early treatment
      routinely involves serial manipulation, followed by adhesive strapping or casting
      of the manipulated foot to hold the correction. Although less than half of
      congenital clubfoot cases treated from birth will respond to serial manipulation
      and casting, it is generally the first choice of treatment. 3. If serial
      manipulation and adhesive strapping or casting do not correct the deformity, then
      surgery, one small part in the ongoing treatment, is necessary. With adequate
      preparation and planning, maximum benefit can be obtained from the surgical
      experience.

PMID- 8140608
TI  - Road to recovery. Post-traumatic stress disorder: the hidden victim.
AB  - 1. Post-traumatic stress disorder (PTSD) is characterized by the development of a
      set of specific symptoms following a psychologically distressing event that is
      outside the range of usual human experience. 2. Recovery does not seem to feel as
      difficult or overwhelming if it is approached "one day at a time." 3. The
      psychologic damage that occurs in PTSD is due primarily to holding the
      experiences inside, "stuffing" them down through various psychodynamics, or
      keeping the experiences subdued through addictive behaviors. 4. PTSD among
      Vietnam veterans is not a mental illness; it is a reaction to extreme stress and
      a reaction to keeping memories stuffed down and not allowed to surface.

PMID- 8140609
TI  - When death takes one of our own. A perioperative experience.

PMID- 8140610
TI  - Surgical intervention during extracorporeal life support.
AB  - 1. Because the patient often is totally dependent on the ECLS circuit and is
      heparinized, an understanding of ECLS greatly improves the nurse's ability to
      interact with the ECLS specialist and surgeon. 2. The surgical nurse should
      instruct the ECLS specialist in the proper techniques for various procedures.
      Similarly, the surgical nurse should become familiar with the working of the ECLS
      circuit and the special terminology used by the ECLS team. 3. The ability to
      communicate and identify the priority of steps of intervention--not only for the
      specialist, but also for the surgical nurse--gives the surgeon the tools to
      resolve the problem quickly and efficiently.

PMID- 8140611
TI  - Ethical sedation.

PMID- 8140612
TI  - How to effectively manage time.

PMID- 8140613
TI  - Preparing children for a surgical experience.
AB  - 1. Little research has been conducted on the specific fears of children
      undergoing surgery. One study reported that the events most remembered about the
      surgical experience were riding to the operating room, receiving injections,
      waking up in pain, and not being allowed to eat or drink. The most feared events
      were injections and the anesthesia mask. 2. Many hospitals have developed formal
      and informal orientation programs for preparing children for surgery. Special
      orientation days with themes may be offered. Films/videos, slide presentations,
      coloring books, photograph albums, puppet shows, and tours often are used to
      introduce the child to the surgical environment. A visit to the operating room
      may be a part of the program. In some cases, play therapy in a mock operating
      room is used. 3. A warm, open, honest environment is crucially important. There
      should be a willingness to discuss the child's ideas, fears, and misconceptions
      concerning their perioperative experience. In addition, children should be given
      the opportunity to learn about their body, the health care profession, and the
      surgical setting.

PMID- 8140614
TI  - Inactivation of MAP kinases.

PMID- 8140615
TI  - Convergent evolution: the need to be explicit.
AB  - Convergence as a phenomenon in molecular evolution is an issue that confuses many
      discussions. Often the problem is that not enough care is taken to state exactly
      what kind of convergence one has in mind. Functional and mechanistic convergence
      are both common, and some structural convergence has probably occurred, but a
      convincing case for genuine sequence convergence has yet to be made.

PMID- 8140616
TI  - Similarities between a soybean nodulin, Neurospora crassa sulphate permease II
      and a putative human tumour suppressor.

PMID- 8140617
TI  - Dicing with death: dissecting the components of the apoptosis machinery.
AB  - Apoptosis, a mode of cell death commonly observed when death is a desirable or
      programmed event, has several characteristic structural features. These features
      appear to be induced by a range of gene products which, together, supervise and
      participate in the controlled dismantling of the cell. In this article the
      molecular components of the apoptotic machinery and the proteins implicated in
      the regulation of this mechanism of cell death are discussed.

PMID- 8140618
TI  - Haloalkane dehalogenase caught in the act.

PMID- 8140619
TI  - Understanding how proteins fold: the lysozyme story so far.
AB  - Hen lysozyme is one of the best characterized and most studied of all proteins.
      Recently, we have used a range of different methods to examine the events
      involved in the in vitro folding pathway of this protein. In this review we show
      that, by combining complementary techniques, it has been possible to piece
      together a detailed model for the folding of this enzyme. Important questions
      prompted by this work are highlighted and we then propose some ideas consistent
      with our data, as well as those of others, which we believe begin to provide
      insight into one of the most intriguing of structural problems in biology--how
      proteins can achieve their complex native forms from disordered denatured states.

PMID- 8140620
TI  - Repression versus activation in the control of gene transcription.
AB  - Studies on the regulation of transcription often focus on mechanisms of
      transcriptional activation. However, transcriptional repression is also an
      important factor in the regulation of many genes. Transcription of specific genes
      can be downregulated in various ways, and examination of a number of different
      systems has revealed that most or all steps required for transcriptional
      activation can be interfered with by transcriptional repressors.

PMID- 8140621
TI  - Role of the beta-amyloid precursor protein in Alzheimer's disease.
AB  - Deposition of beta-amyloid peptide in the brain is an early event in Alzheimer's
      disease, the most common cause of dementia. Studies of the beta-amyloid precursor
      protein (APP), which gives rise to beta-amyloid, are rapidly leading to a better
      understanding of the biochemical basis of the disease--a prerequisite for
      rational drug development.

PMID- 8140622
TI  - Kit wars.

PMID- 8140623
TI  - The SRCR superfamily: a family reminiscent of the Ig superfamily.

PMID- 8140624
TI  - Molecular imprinting.
AB  - Molecular imprinting is an emerging methodology for the creation of selective
      recognition sites in synthetic polymers. This technique entails the
      polymerization of functional monomers in the presence of an important molecule
      (template). Recent studies have shown that the polymers obtained exhibit a
      surprisingly high degree of stereo- and regiospecific selectivity, making the
      commercial use of such tailor-made separation materials in several areas, such as
      the chiral separation of bioactive molecules and as antibody mimics, a realistic
      possibility.

PMID- 8140625
TI  - Modification of rejection by polyethylene glycol in small bowel transplantation.
AB  - The use of polyethylene glycol (PEG) in preservation solutions has been
      associated with a decreased incidence of rejection in clinical and experimental
      organ transplantation. In this study, we examined the effect of PEG with
      different molecular configurations on rejection of small bowel allografts in the
      rat. Male ACI and LEW rats were used as donors and recipients, respectively.
      Orthotopic small bowel transplantation was performed using the following
      preservation solutions: lactated Ringer's solution (n = 7), University of
      Wisconsin solution (n = 7), University of Wisconsin solution without hydroxyethyl
      starch (sUW; n = 7), sUW with PEG20M (n = 9), sUW with PEG8000 (n = 6), and sUW
      with PEG20L (n = 7). No immunosuppression was given. In orthotopic small bowel
      transplantation, only groups with a high molecular weight PEG, PEG20M and PEG20L,
      demonstrated longer survival (P < 0.01 and P < 0.001, respectively) and delayed
      onset of unkempt appearance (P < 0.05 and P < 0.001, respectively). In
      heterotopic small bowel transplantation, sUW was compared with sUW with PEG20L.
      Rejection occurred later and its progression was slower in the sUW with PEG20L
      than in the sUW alone. Our observations suggest that the onset and progression of
      rejection after small bowel transplantation were influenced by the molecular
      weight and configuration of the PEG molecule. The mechanism is unclear, but high
      molecular weight PEG appears to reduce or change the immunogenicity of the small
      bowel allograft.

PMID- 8140626
TI  - Evaluation of preservation conditions and various solutions for small bowel
      preservation.
AB  - The aim of the study was to delineate the most optimal preservation conditions
      for small bowel grafts. Established preservation solutions such as EuroCollins,
      University of Wisconsin, histidine-tryptophane-ketoglutarate-Brettschneider,
      phosphate-buffered sucrose (PBS 140), and 3 new solutions--extracellular fluid
      (ECF), lactobionate fructose, and a modified lactobionate fructose solution--were
      compared with saline to determine the most optimal solution for the intestine.
      Recipient survival, standard histology, and glutaminase activity were used to
      assess the degree of injury encountered after 12 hr of preservation followed by
      transplantation. To evaluate the various preservation conditions, ECF was used at
      pH 6.8 (original ECF). Grafts were preserved most optimally when a vascular
      washout after the cold storage period was omitted and when topical rewarming of
      the graft with 37 degrees C saline before reperfusion was performed. Graft
      survival was not significantly different after preservation with any solution
      tested (50-83%). Highest graft survival (83%) was achieved with lactobionate
      fructose and PBS140. Histologic evaluation 20 min after reperfusion revealed
      minor differences between most groups; a slight advantage was observed for PBS140
      preserved grafts. Mucosal glutaminase activity of PBS140-preserved grafts was
      significantly higher 20 min after reperfusion compared with any other solution
      evaluated, indicating a superior graft function. These data indicate that
      different preservation conditions have a great impact on postoperative graft
      survival and that PBS140 might be preferable to any of the other preservation
      solutions tested.

PMID- 8140627
TI  - Protective effect of preservation of canine pancreas by the two-layer (University
      of Wisconsin solution/perfluorochemical) method against rewarming ischemic injury
      during implantation.
AB  - Rewarming ischemia during implantation severely compromises posttransplant
      pancreas graft survival because the graft has already been subjected to warm and
      cold ischemia before implantation. The purpose of this study was to examine
      whether preservation of the pancreas graft by the two-layer method ameliorates
      rewarming ischemic injury of the graft during implantation using a canine model.
      After flushing with cold University of Wisconsin solution (UW), the pancreas
      grafts were preserved by the two-layer (UW/perfluorochemical [PFC]) method (group
      1) or simple cold storage in UW (group 2) for 24 hr and then autotransplanted. In
      control, the pancreas grafts were flushed out with cold UW and immediately
      autotransplanted without preservation (group 3). After completion of vascular
      anastomosis, vascular clamp was not released until 90, 120, or 150 min of
      rewarming ischemia, including anastomosis time, had elapsed. After 90 min of
      rewarming ischemia, graft survival rates were 5/5, 100%, 5/5, 100%, and 5/5,
      100%, in groups 1, 2, and 3, respectively. After 120 min, all the grafts in
      groups 2 and 3 failed (0/5, 0%, and 0/5, 0%, respectively); however, all the
      grafts in group 1 survived (5/5, 100%). Even after 150 min, 1 of 3 grafts in
      group 1 survived (1/3, 33%). After 24 hr preservation, tissue ATP levels of the
      grafts in group 1 were about 2-fold the reference values before harvesting (8.23
      +/- 0.72 vs. 4.44 +/- 0.49 mumol/g dry weight, P < 0.05) and significantly higher
      compared with group 2 (8.23 +/- 0.72 vs. 1.76 +/- 0.52 mumol/g dry weight, P <
      0.01). After 120 min of rewarming ischemia, tissue ATP levels in group 1 were 84%
      of the reference values and significantly higher compared with group 2 (3.75 +/-
      0.25 vs. 1.57 +/- 0.48 mumol/g dry weight, P < 0.05). Two hours after
      reperfusion, ATP levels in group 1 were 42% of reference values but significantly
      higher compared with group 2 (1.86 +/- 0.36 vs. 1.03 +/- 0.18 mumol/g dry weight,
      P < 0.05). We conclude that the two-layer (UW/PFC) method ameliorates rewarming
      ischemic injury of the pancreas graft during implantation by increasing tissue
      ATP contents during preservation and consequently maintaining tissue ATP levels
      during implantation.

PMID- 8140628
TI  - Erythrocytosis after renal transplantation. The response to theophylline
      treatment.
AB  - Erythrocytosis was found in 20 out of 127 patients who underwent renal
      transplantation (15.7%). Four were found to have elevated erythropoietin
      concentrations (139.7 +/- 22.0 microns/ml) and 7 had normal levels (52.3 +/- 84
      microns/ml (normal -60). The growth of erythroid CFUs was found to be normal in
      all patients. Theophylline treatment was given to 11 patients. The patients were
      divided into 3 groups according to their response: (1) patients with high
      erythropoietin levels whose hematocrit decreased from 59.6% to 46.3% within 2
      weeks of treatment in parallel with a fall in erythropoietin; (2) patients with
      normal erythropoietin levels in whom theophylline therapy reduced the hematocrit
      from 58.7% to 47.2%; and (3) patients in whom theophylline had no effect on their
      erythrocytosis. We conclude that erythrocytosis after renal transplantation is a
      heterogenous condition and that several mechanisms are involved. In some
      patients, high erythropoietin levels or high sensitivity to erythropoietin are
      associated with the erythrocytosis. Theophylline therapy is beneficial in more
      than 50% of the cases.

PMID- 8140629
TI  - L-Arginine deficiency after liver transplantation as an effect of arginase efflux
      from the graft. Influence on nitric oxide metabolism.
AB  - L-Arginine plays an important role in protecting animals against ammonia
      intoxication, enhances immune function, stimulates wound healing, and is the
      precursor for the endothelium-derived relaxing factor, recently recognized as
      nitric oxide (NO). In this study, we investigated the influence of hepatic
      reperfusion on amino acid metabolism after human OLT. After 10 sec of
      reperfusion, the arterial plasma levels of L-arginine dropped from 105 +/- 12
      mumol/L to 3.8 +/- 0.6 mumol/L (P < 0.001), whereas plasma ornithine increased
      from 40 +/- 5.5 mumol/L to 129 +/- 15 mumol/L (P < 0.001). The reduced L-arginine
      levels remained subnormal for several hours after OLT. This drop in plasma L
      arginine was due to an arginase release from the implanted graft. Immediately
      after reperfusion, the plasma concentrations of arginase increased from
      pretransplantation values of 18 +/- 13 IU/L to 2384 +/- 1456 IU/L (P < 0.01).
      Measurement of plasma nitrite (NO2-) and nitrate (NO3-), which are the stable end
      products of NO, revealed that NO2- decreased about 50% after reperfusion (from
      1.64 +/- 0.32 mumol/L to 0.80 +/- 0.17 mumol/L; P < 0.001), whereas NO3- levels
      remained unchanged (76 +/- 23 mumol/L vs. 63 +/- 8 mumol/L). We conclude that
      hepatic reperfusion causes L-arginine deficiency by liberating high amounts of
      arginase from the implanted graft. This L-arginine depletion may influence the NO
      synthesis in patients after OLT.

PMID- 8140630
TI  - Donor thyroid function does not affect outcome in orthotopic liver
      transplantation.
AB  - Brainstem death is associated with endocrine and metabolic alterations that can
      result in donor hemodynamic instability. It has been suggested that these changes
      can be reversed through hormonal manipulation of the donor. We measured thyroid
      hormone levels (free triiodothyronine [fT3], free tetraiodothyronine [fT4],
      reverse triiodothyronine) and thyroid-stimulating hormone (TSH) in 50 consecutive
      adult brain dead multiorgan donors. Recipient graft function was assessed using
      peak and day 5 aspartate aminotransferase, peak serum bilirubin, and minimum
      prothrombin time during the first week after OLT. Free T3 was low in 32/50 donors
      and was associated with a low fT4 in 24 cases. TSH was normal in 35 donors and we
      found no correlation between TSH levels and fT3 or fT4. Reverse triiodothyronine
      was normal or high in 96% of donors. Patient and graft survival were 96% for both
      the low and high fT3 groups. These data suggest that euthyroid sick syndrome is
      the most likely cause for the endocrine and metabolic alterations seen in
      brainstem-dead donors. This does not appear to influence liver recipient or graft
      survival.

PMID- 8140631
TI  - Cytotoxic T lymphocyte precursor frequency does not correlate with either the
      incidence or severity of graft-versus-host disease after matched unrelated donor
      bone marrow transplantation.
AB  - BMT from matched unrelated donors or mismatched family members is associated with
      an increased risk of graft-versus-host disease (GVHD) compared with HLA-identical
      sibling donors. It has been suggested that the level of patient-specific CTL
      precursors (CTLp) present in matched unrelated donors correlates with the
      incidence and severity of GVHD after BMT. This study group consisted of 17
      patients who all received unmanipulated bone marrow from an HLA-A,B,DR-matched
      unrelated donor. Patient-specific CTLp frequencies were estimated in the donor
      before transplant. The CTLp frequencies were then compared with the incidence and
      severity of GVHD experienced by the patient after transplantation. Statistical
      analysis revealed no correlation between donor precursor frequencies and the
      patient developing clinically significant acute GVHD after transplantation (X2 =
      1.16). This study suggests that caution should be used before the inclusion of
      the CTLp frequency result in the clinical decision of selecting the most suitable
      matched unrelated donor for BMT. CTLp frequency does not correlate with either
      the incidence or severity of GVHD after matched unrelated donor BMT.

PMID- 8140632
TI  - Polysaccharide conjugate vaccine responses in bone marrow transplant patients.
AB  - Bone marrow transplant patients have impaired responses to pure polysaccharide
      (PS) vaccines and are at an increased risk for disease caused by PS encapsulated
      pathogens such as Haemophilus influenzae type B (HIB) and Streptococcus
      pneumoniae. We immunized 35 BMT patients (21 allogeneic and 14 autologous) ages 2
      45 years with pure PS pneumococcal (Pnu-imune 23) HIB-conjugate (HibTITER), and
      tetanus toxoid vaccines. Patients were assigned to receive vaccines at either 12
      and 24 months after transplantation or at 24 months only. Only 19% of all
      enrolled patients developed protective antibody concentrations (> or = 0.300
      microgram antibody nitrogen/ml) to the 6 pneumococcal serotypes measured after
      the 24-month immunization. Poor response to pneumococcal vaccine was not
      different for the 2 study groups and was similar to previous studies. In
      contrast, HIB-conjugate vaccine elicited protective concentrations of antibody (>
      or = 1.0 microgram/ml) in 56% of patients after 1 dose and in 80% after 2 doses.
      The group that received 2 doses of HIB-conjugate vaccine had a significantly
      higher geometric mean antibody concentration of 14.5 micrograms/ml as compared
      with 1.43 micrograms/ml for those receiving only 1 dose (P = 0.012). Responses to
      tetanus toxoid vaccine were similar to HIB-conjugate vaccine, with a booster
      response documented after the second dose. In summary, 2 doses of HIB-conjugate
      vaccine given at 12 and 24 months after transplantation produced protective
      antibody concentrations in 80% of patients. While the response to pure PS
      pneumococcal vaccine was poor, the results with HIB-conjugate vaccine suggest
      that future pneumococcal conjugate vaccines may also benefit BMT patients.

PMID- 8140633
TI  - The pig as a potential organ donor for man. A study of potentially transferable
      disease from donor pig to recipient man.
AB  - Ten pigs, reared in an unmodified laboratory animal house environment, have been
      investigated to ascertain the incidence of diseases or disorders, including
      infection, neoplasia, or metabolic abnormalities, that might preclude the
      transplantation of major organs from the pig to man. Noninvasive studies were
      performed in the second month of life (study 1) and repeated after an interval
      that varied between 3 and 5 1/2 months (study 2). Necropsy was then performed as
      a means of assessing the accuracy of the 2 screening examinations. A total of 150
      tests were performed on each pig. At both studies the feces contained cysts
      and/or trophozoites of several parasites, all of which were considered
      commensals. No other organisms potentially infective for man were identified
      either at study or at necropsy. Neither congenital anomalies nor malignant
      neoplasia was found at necropsy. However, in 2 pigs a vasculitis of uncertain
      etiology was present in the kidneys on microscopic examination, and in one of
      these the same condition affected the heart. This pathology was suspected neither
      from the screening examinations nor from the macroscopic appearance of these
      organs. Biopsy and microscopic examination would therefore appear to be essential
      before any organ is transplanted into a human.

PMID- 8140634
TI  - Alloantigenicity of human endothelial cells. IV. Derivation, characterization,
      and utilization of gonadal vein endothelia to control endothelial
      alloantigenicity during lymphocyte-endothelial interactions.
AB  - Most previous studies to evaluate endothelial cell-T lymphocyte interactions have
      used human peripheral blood as a source of T lymphocytes and human umbilical vein
      endothelial cells as a source of endothelia. Implicit in this experimental system
      are allogeneic lymphocyte-endothelial interactions, which are largely ignored. To
      overcome this problem, we isolated gonadal vein endothelial cells (GVEC) along
      with matched splenic macrophages and T lymphocytes from cadaveric donors, thus
      providing a completely autologous series of cells for experimentation. First,
      GVEC were analyzed for morphology, surface phenotype, and cytokine mRNA
      expression, and found to be indistinguishable from human umbilical vein
      endothelial cells. Using this system, we observed that irradiated GVEC were able
      to promote a 2- to 3-fold increase in the proliferation of matched autologous
      splenic T cells after PHA stimulation. This indicates that the costimulator
      activity of endothelial cells reported by others is an intrinsic property of
      endothelial cells, and is not a consequence of endothelial alloantigens. We also
      used this system to assess the relative abilities of GVEC and macrophages
      obtained from the same donor to stimulate the proliferation of purified
      allogeneic CD3+ PBL. We found the following hierarchy of alloantigenicity in this
      experimental system: splenic macrophages > IFN-gamma-treated GVEC >> untreated
      GVEC = TNF alpha-treated GVEC. These studies demonstrate that allogeneic
      macrophages are intrinsically more antigenic than endothelial cells derived from
      the same donor. Furthermore, they illustrate the utility of this experimental
      system to obtain data regarding lymphocyte-endothelial interactions that are
      otherwise unobtainable.

PMID- 8140635
TI  - Capacity of simian virus 40 T antigen to induce self-tolerance but not
      immunological privilege in the anterior chamber of the eye.
AB  - Transgenic mice bearing the simian virus 40 (SV40) large T oncogene developed
      progressively growing intraocular tumors and displayed characteristics of
      immunological tolerance to SV40 T antigen. Transgenic mice failed to mount CTL
      responses to SV40 T antigen-bearing tumor cell lines derived from the transgenic
      intraocular tumors. Spleen cells from transgenic hosts were able to prevent the
      in vivo and in vitro generation of CTL responses by lymphocytes from normal
      syngeneic FVB/N mice. Adoptive transfer of spleen cells from tolerant transgenic
      donors temporarily inhibited the immunological rejection of SV40 T antigen
      positive tumor cells transplanted to normal syngeneic FVB/N recipients. Thus,
      introduction of SV40 transforming sequences into the mouse germline induced
      tolerance to SV40 T antigen. However, in normal FVB/N mice, SV40 T antigen
      bearing tumor cells failed to experience immune privilege in the anterior chamber
      and did not elicit systemic down-regulation of delayed-type hypersensitivity
      responses that characteristically occur when antigens are introduced into the
      anterior chamber. The results indicate that within the anterior chamber of the
      eye, SV40 T antigen-bearing cells are perceived by the host's immune system much
      differently than are other categories of antigen. Thus, SV40 T antigen
      effectively induces self-immunological tolerance when its gene is introduced into
      the host's germline but fails to experience immunological privilege in the
      anterior chamber of the eye in normal hosts.

PMID- 8140636
TI  - Evidence that intrathymic islet transplantation does not prevent diabetes or
      subsequent islet graft destruction in RT6-depleted, diabetes-resistant
      BioBreeding/Worcester rats.
AB  - Pancreatic islet allografts transplanted intrathymically are accepted and restore
      normoglycemia in streptozotocin-diabetic rats given one injection of
      antilymphocyte serum. Intrathymic allografts similarly restore normoglycemia in
      diabetes-prone (DP) Bio-Breeding (BB) rats that have developed spontaneous
      autoimmune diabetes. Intrathymic islets also reduce the frequency of subsequent
      diabetes when transplanted prophylactically into young DP rats. These findings
      suggest that intrathymic transplantation can prevent not only allograft
      rejection, but also the appearance and recurrence of autoimmune tissue
      destruction. To explore these hypotheses further, we attempted both to confirm
      previous studies and to extend them to another model of autoimmune diabetes, the
      RT6-depleted diabetes-resistant (DR) BB rat. Fewer than 1% of DR-BB rats develop
      spontaneous diabetes, but most become hyperglycemic after in vivo immune
      elimination of RT6+ T cells. Using the protocols described in the literature, we
      observed the following: (1) Consistent with previous reports, intrathymic islet
      allografts survived indefinitely in streptozotocin-diabetic, antilymphocyte serum
      treated, non-BB recipient rats. (2) Consistent with previous reports, intrathymic
      islet grafts produced long-term normoglycemia in diabetic DP-BB rats and also
      reduced the frequency of spontaneous diabetes in young animals transplanted
      prophylactically. (3) In contrast, intrathymic islets (iso- and allografts)
      neither prevented nor reversed diabetes in RT6-depleted DR rats. We hypothesize
      that intrathymic islet grafts survive in DP-BB rats because they are lymphopenic
      and immunocompromised, whereas immunocompetent diabetic DR rats successfully
      recapitulate the autoimmune disease process. Although intrathymic allograft
      transplantation is postulated to induce a state of tissue-specific tolerance, our
      results indicate that this tolerant state may not extend to autoimmune
      destruction of either isografts or allografts.

PMID- 8140637
TI  - Use of spiral computed tomography in the diagnosis of transplant renal artery
      stenosis.

PMID- 8140638
TI  - Transplantation of kidneys from a donor with microscopic polyarteritis: treatment
      and outcome in two recipients.

PMID- 8140639
TI  - Rejection in HLA-identical living related donor kidney transplants: lack of
      predictive immunologic parameters.

PMID- 8140640
TI  - Improved technique for transduodenal pancreas transplant biopsy.

PMID- 8140641
TI  - Glomerular hyperfiltration as a nonimmunologic mechanism of progression of
      chronic renal rejection.

PMID- 8140642
TI  - Rejection patterns after simultaneous pancreaticoduodenal-kidney transplants in
      pigs.

PMID- 8140643
TI  - Current limitations to use of major histocompatibility complex transgenic donors
      for islet transplantation.

PMID- 8140644
TI  - Evidence that heat-treated antigen-presenting cells induce hyporesponsiveness in
      allogeneic T cells.

PMID- 8140645
TI  - Renal morphological changes in dogs with systemic venous drainage of the
      pancreas.

PMID- 8140646
TI  - Release of endothelial cell-associated heparan sulfate proteoglycan by activated
      T cells.

PMID- 8140647
TI  - Chronic cyclosporine-induced nephrotoxicity: a rabbit model.

PMID- 8140648
TI  - Evidence that combination therapy using cobra venom factor, splenectomy, and
      deoxyspergualin is effective in guinea pig to rat cardiac xenotransplantation.

PMID- 8140649
TI  - The effect of minor ABO mismatches on the incidence of graft-versus-host disease
      after allogeneic bone marrow transplantation.

PMID- 8140650
TI  - Neurotoxins: nature's untapped bounty.

PMID- 8140651
TI  - Further evidence for adenosine A3 receptors.

PMID- 8140652
TI  - Adenosine A3 receptors in mast cells.

PMID- 8140653
TI  - Wither, whether and whither pharmacology.
AB  - There has been considerable discussion over the last couple of years about the
      nature of pharmacology as a discipline and the training programmes for
      pharmacologists. Recently the British Pharmacological Society devoted a whole
      symposium to this important issue. In the UK in particular, pressure from
      government has nearly doubled the number of undergraduate students entering the
      university sector over the last five years, which has put considerable pressure
      on the teaching of essential practical courses for this experimental discipline.
      Similar pressures face the teaching of pharmacology in other countries and the
      situation, discussed here by Clive Page, Morley Sutter and Michael Walker,
      clearly has implications for academic pharmacology and the pharmaceutical
      industry. It is intended that the following article will stimulate both dialogue
      and positive action towards redressing this important problem.

PMID- 8140654
TI  - Protection of the heart by ischaemic preconditioning: mechanisms and
      possibilities for pharmacological exploitation.
AB  - Ischaemic preconditioning can be defined as the protective adaptive mechanism
      produced by short periods of ischaemic stress resulting in a marked, albeit
      temporary, resistance of the myocardium to a subsequent more prolonged period of
      that same stress. This protection includes reductions in ischaemic cellular
      damage and in life-threatening ventricular arrhythmias. The most likely
      mechanisms for this protection are discussed in this review by James Parratt and
      involve the release of endogenous substances from the ischaemic myocardium (for
      example, adenosine, bradykinin, nitric oxide and prostacyclin) with the possible
      involvement of ATP-dependent K+ channels, Gi proteins and protein kinase C. If we
      understood more fully the precise mechanisms of this pronounced protection, it
      should be possible to exploit them pharmacologically to ultimate therapeutic
      advantage.

PMID- 8140655
TI  - Urokinase-type plasminogen activator and its receptor: new targets for anti
      metastatic therapy?
AB  - Urokinase-type plasminogen activator (uPA) and its receptor are instrumental in
      cell invasion and metastasis; their high levels of expression in human tumours
      correlates with a high risk of recurrence. uPA has a pleiotropic effect on cell
      migration and spreading in vivo and in vitro through the activation of
      plasminogen or other protein factors at the cell surface or in the extracellular
      matrix. Three specific inhibitors, with different tissue-specificities and
      regulatory properties, modulate cell-surface exposure of uPA activity. Overall,
      uPA is at the centre of a complex system affecting cell movement and
      invasiveness, and inhibition of uPA is now a goal of anti-metastatic therapy. The
      role of uPA and its inhibition are discussed in this review by Francesca Fazioli
      and Francesco Blasi.

PMID- 8140656
TI  - The human beta 3-adrenoceptor: the search for a physiological function.

PMID- 8140657
TI  - Re-evaluation of bacteriorhodopsin as a model for G protein-coupled receptors.

PMID- 8140658
TI  - Is endothelin-induced vasoconstriction mediated only by ETA receptors in humans?

PMID- 8140659
TI  - [Costs of cancer chemotherapy].

PMID- 8140660
TI  - [Treatment of drug-induced nausea and vomiting].
AB  - Patients consider nausea (N) and vomiting (V) as severe adverse events to
      chemotherapy (CT). The introduction of the 5-HT3 antagonists have added a new
      dimension to the treatment of acute N and V. A review of the pathophysiology of N
      and V induced by CT and of the prescription of antiemetics used in Denmark is
      given. Dopamine D2 antagonists such as metoclopramide and metopimazine have a
      moderate antiemetic effect, when given in conventional low doses. A combination
      of one of these drugs and a steroid is recommended as first choice in patients
      receiving moderately emetogenic CT. In severe emetogenic CT, especially cisplatin
      based, the 5-HT3 antagonists have resulted in a significant improvement and
      ondansetron, granisetron or tropisetron are in these patients recommended as
      first choice, either given alone or in combination with steroids. The duration of
      such a treatment should be restricted to the first 24 hrs after CT, as none of
      these expensive drugs seem to improve treatment of delayed emesis. The best known
      treatment of delayed emesis is the combination of a dopamine D2 antagonist and a
      steroid. Many pathophysiological and clinical questions are unanswered. Future
      trials using correct methodology should focus on patients receiving multiple-day
      CT, patients receiving multiple cycles of CT and on patients resistant to first
      line antiemetic treatment.

PMID- 8140661
TI  - [Nicotinamide and prevention of insulin-dependent diabetes mellitus. Rationale,
      effects, toxicology and clinical experiences. ENDIT Group].
AB  - IDDM is caused by an immune-mediated destruction of the insulin-producing beta
      cells. Beta cells are destroyed by induction of oxygen-derived free radicals (FR)
      and nitric oxide (NO), which results in perturbation of the mitochondrial
      respiratory system and DNA strand breaks. As a result of beta cell destruction,
      islet cell antibodies (ICA) can be demonstrated in the circulation. These
      antibodies can be detected up to eight years prior to overt IDDM. Nicotinamide, a
      vitamin B3 derivative, interferes with the immune mediated beta-cell destruction
      by reducing the content of FR and NO and thereby reducing their deleterious
      effects. At the same time, nicotinamide increases the intracellular NAD pool,
      thus increasing the energy supply of the cell. Nicotinamide protects against
      chemically induced as well as spontaneous diabetes in animal models of the
      disease. Recently, open clinical studies have suggested that nicotinamide when
      administered to humans can prevent or delay clinical onset of IDDM. To test the
      possible preventive effect of nicotinamide in IDDM, a prospective, randomized,
      placebo-controlled study is needed. A multicentre study including 18 European
      countries, Israel and Canada is planned to start during 1993.

PMID- 8140662
TI  - [Technique of induced abortion, abrasion and vacuum extraction. Clinical trial of
      Ambu Twin Pump 1000].
AB  - Ambu Twin Pump 1000 is a suction pump designed for pharyngeal and tracheal
      suction in emergency situations. The pump can be operated by foot or by hand. The
      object of this test was to evaluate the applicability of the pump in performing
      legal abortion (before 13th. week), suction curettage and vacuum extraction, in
      places where electricity is not available; thus especially for use in Third World
      countries. The evaluation of the pump concerned the suction capacity, the
      stability on the support and finally ease of dismantling and cleaning. It is
      concluded that Ambu Twin Pump 1000 are easy to use and has sufficient suction
      capacity for the mentioned purposes. For induced abortion the pump was provided
      with a 200 ml reservoir for cleaning purposes.

PMID- 8140663
TI  - [Is routine microscopy of tissue from induced abortions necessary?].
AB  - This study was performed in order to evaluate the importance of routine
      microscopy of tissue from legal abortions performed before the end of the 12th
      week of pregnancy. The tissues recovered from 580 abortions were examined
      carefully macroscopically before they were sent to microscopy. Five hundred and
      fifty-four samples (95.5%) were judged by macroscopic examination to contain the
      normal products of pregnancy. These all contained chorionic villi when examined
      histologically. Macroscopic examination was inconclusive in the remaining 26
      samples (4.5%), 22 of these samples proved after all to contain chorionic villi
      when examined histologically. We conclude that histological examination of tissue
      from legal abortions is unnecessary in most cases if it is replaced by careful
      clinical examination of the sample, only to be followed by microscopy if the
      findings are uncertain.

PMID- 8140664
TI  - [Status of preventive screening for uterine cervix cancer in Denmark in 1994].
AB  - In 1986 The National Board of Health published guidelines for cervical cancer
      screening in Denmark. These guidelines recommend organized screening with
      personal invitations every three years to women in the age group 23-59 years, and
      in the years to come also invitation of women aged 60-74 years. We studied the
      organization of cervical cancer screening in Danish counties at the beginning of
      1994. Organized screening programmes are running in 15 out of the 16 "counties"
      (this include the municipalities of Kobenhavn and Frederiksberg). Four counties
      completely follow the national guidelines. Eight counties follow these guidelines
      in general, but they do not invite women above the age of 60 years. In total, 72%
      of women aged 25-74 years are at present invited for cervical cancer screening in
      Denmark.

PMID- 8140665
TI  - [Esophageal resections in Denmark 1985-1988. A retrospective study of
      complications and early mortality].
AB  - In a retrospective investigation, 17 Danish Departments of Surgery reported on
      morbidity and mortality following surgical treatment of cancer of the oesophagus
      and cardia in the years 1985-1988. The study comprised 352 men and 112 women,
      representing 98% of the total number of resections performed in Departments of
      General Surgery (11%), Departments of Surgical Gastroenterology (24%) and
      Departments of Thoracic Surgery (65%). Nine departments performed less than five
      resections per year. Frequency of anastomotic leaks were 8.2%, and the mean
      hospital mortality was 16.6%. Mortality was significantly lower (median 9.6% and
      7.0%) in departments performing more than 20 resections per year. It is concluded
      that in Denmark, surgical treatment of cancer of the oesophagus or cardia should
      be centralized to departments performing more than 20 resections per year.

PMID- 8140666
TI  - [Thrombolysis and acute myocardial infarction. Reduced residual ischemia in first
      acute myocardial infarction].
AB  - In order to assess the effect of thrombolysis on residual myocardial ischaemia,
      we prospectively performed maximal exercise testing and ambulatory ST-segment
      monitoring in a consecutive series of 123 men recovering from a first acute
      myocardial infarction (AMI). Seventy-four patients fulfilled our criteria for
      thrombolysis, but only 35 patients received thrombolytic agents, whereas 39 were
      conservatively treated (controls). In 49 patients thrombolytic therapy was not
      indicated. Thrombolysis resulted in a non-significant reduction in the prevalence
      of exercise-induced ST-segment depression: 43% in reperfused patients versus 62%
      in controls. During 36-hour ambulatory ST-segment monitoring, however, the
      duration of myocardial ischaemia was significantly reduced in thrombolyzed
      patients: 322 minutes versus 1144 minutes in controls (p < 0.05). Exercise
      testing revealed a higher maximal work capacity in thrombolyzed patients compared
      with controls: 160 +/- 41 versus 139 +/- 34 W (p < 0.02). No difference was found
      in left ventricular ejection fraction between the two subgroups. We conclude,
      that thrombolysis given for a first AMI reduces residual myocardial ischaemia.
      The reduced ischaemic burden is assumed to be the pathophysiologic mechanism
      underlying the also observed improvement in exercise tolerance.

PMID- 8140667
TI  - [T3 thyrotoxicosis in a patient with a hormonally active, metastasizing
      follicular thyroid carcinoma].

PMID- 8140668
TI  - [Thrombocytopenia in cytomegalovirus infection].
AB  - A case of a 15 month old female patient with thrombocytopenic purpura induced by
      postnatally acquired Cytomegalovirus (CMV) infection is described. Treatment with
      intravenous immunoglobulin caused a satisfactory but short-lived attainment of
      normal platelet count. Spontaneous recovery took place after ten months. A review
      of the literature up to 1993 revealed that medical treatment of severe
      thrombocytopenia in normal hosts with the same aetiology had been reported in
      only five cases, Prednisone treatment was given in four cases (all adults), with
      no apparent effect on platelet count. Persistent severe thrombocytopenia in a one
      year-old child responded to repeated intravenous infusions of immunoglobulin.

PMID- 8140669
TI  - [Functional disability, handicap and coping].

PMID- 8140671
TI  - [Hormones to the the older generation].

PMID- 8140670
TI  - [Strategy of ulcer therapy--should the debate forum be in the court or office?].

PMID- 8140672
TI  - [Molgramostim (rhGM-CSF)--a hematopoietic growth factor for the treatment of
      neutropenia].

PMID- 8140673
TI  - Glycine loading and urinary oxalate excretion.
AB  - One metabolic pathway for glycine leads to glyoxylate which is the precursor of
      oxalate. To investigate whether absorption of glycine solution in transurethral
      operations may promote precipitation of calcium oxalate stones, we collected
      urine for 24 h before and after an intravenous infusion of 22 g of glycine in 10
      male volunteers. There were no significant changes in the urinary excretion of
      oxalate, calcium, or citrate. Urine volume and amino acid excretion increased,
      while the urine contained less potassium. These results provide no biochemical
      evidence of an increased risk of renal lithiasis due to glycine irrigation during
      transurethral operations.

PMID- 8140674
TI  - Extracorporeal shock wave lithotripsy using the Dornier MPL 9000 lithotriptor.
AB  - 336 patients with urinary calculi were treated between June 1988 and October 1991
      with extracorporeal shock wave lithotripsy using the Dornier MPL 9000
      lithotriptor. Of 352 renal units (a kidney and its ureter), 286 had renal stones,
      62 had ureteral stones and 10 had both. There were radiolucent stones in 6 units.
      The complete disintegration rate was 94%. The mean number of shock waves was
      2,973, the range being from 300 to 16,131. In 310 of 447 (64%) sessions,
      treatment was done without any anesthesia. The rate of complete removal was 67.3%
      3 months after the last treatment. Only 11 patients required supplementary
      treatment consisting of percutaneous nephrolithotripsy and transurethral
      lithotripsy. There were no severe complications except subcapsular hematomas
      observed in 2 patients. The Dornier MPL 9000 is a useful lithotriptor for the
      treatment of urinary calculi, except staghorn calculi.

PMID- 8140675
TI  - Incidence of pouch stones and risk factors for urolithiasis in patients with
      continent urinary diversion or neobladder using intestine.
AB  - Urinary risk factors and inhibiting factors for urolithiasis, such as oxalate,
      calcium, phosphate, uric acid, citrate, and magnesium, were examined in 12
      patients receiving continent urinary diversion, neobladder, or augmentation
      cystoplasty using intestine. These data were compared with the incidence of pouch
      stone formation. Ten (83.3%) of 12 patients had at least one risk factor, and 5
      (41.7%) of 12 had two or more risk factors. Pouch stone developed in 4 (80%) of 5
      patients with two or more risk factors, and in none of 7 patients with one or
      zero risk factors. The incidence of pouch stone in the former group was
      significantly higher than in the latter group. These results suggest that urinary
      reservoir operations should not be performed in patients with two or more risk
      factors for urolithiasis.

PMID- 8140676
TI  - Behavior of different suture materials in the urinary bladder of the rabbit with
      special reference to wound healing, epithelization and crystallization.
AB  - Five urinary bladder incisions were performed in 16 rabbits and the defects
      closed by plain catgut 4-0, chromic catgut 4-0, polypropylene 4-0, polyglactin
      910 4-0 and polyglactin 910 8-0 in the form of an all-layer suture, thereby
      obtaining a total of 80 suture sites. The running sutures in 8 animals were
      reviewed by light microscopy after 1, 2, 7 and 15 weeks, and in 8 additional
      animals after 3 days, 1, 2, 7 and 15 weeks by scanning electron microscopy.
      Moreover, we analyzed and compared the autopsy findings on gross inspection, the
      urinary sediments and urinary cultures of the individual animals. Scanning
      electron-microscopic evaluations showed that epithelization of the intraluminal
      suture portions can be accomplished after 3 days already. Reduced suture strength
      and rapid absorption of the suture material prevent later postoperative
      incrustations. Light-microscopic inspection of the segments of the bladder wall
      bearing this suture material suggests that a minor inflammatory tissue response
      around the suture material--with polyglactin 910 8-0 in particular--is more
      likely to enhance regeneration of the tunica muscularis and to prevent formation
      of cysts than seen with a long-standing highly inflammatory tissue response
      around the suture site of catgut threads. In the animal experiment, the
      polyglactin 910 suture has shown sufficient firmness and proved to be superior to
      any other suture material as regards the reaction to foreign bodies and
      inclination to incrustation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140677
TI  - HLA antigens in Peyronie's disease.
AB  - This study presents data on HLA phenotypes of 52 unrelated patients suffering
      from idiopathic Peyronie's disease. This first investigation on HLA class II
      antigens detected an association of HLA-DR3 and -DQw2 in this disorder. HLA
      typing was done from ACD-stabilized peripheral blood using the modified
      lymphocytotoxicity test. Antigen frequencies of the patient group were compared
      with those of healthy individuals of the local population. There were no
      deviations of frequencies for antigens of the B7 cross-reacting group as
      described in earlier studies. In addition none of the other class I antigens (HLA
      A, -B, -C) showed any significant deviation in frequencies after correction of p
      values. Regarding class II antigens HLA-DR3 was detected in the patient group in
      33.3% compared with 16.0% of the control population (corrected p < 0.05). The
      closely linked antigen DQw2 was found in 58.8 compared with 31.2% (corrected p <
      0.005). Not only genetic factors can be stated by these findings. As HLA-DR3 and 
      DQw2 are known to be the typical associated antigens of organospecific autoimmune
      disorders, this suggests possible autoimmunological factors in this disorder of
      otherwise unknown etiology.

PMID- 8140678
TI  - Spontaneous rupture of the urinary bladder complicated by extensive fascitis: the
      importance of a high index of suspicion.
AB  - Spontaneous rupture of the urinary bladder is a rare entity. This is, in part,
      the cause for the low rate of correct preoperative diagnosis, the high rate of
      delayed diagnosis, morbidity and mortality. We report a case of spontaneous
      rupture of the urinary bladder in an adult patient, complicated by extensive
      fascitis of the abdominal wall. The stormy course and long hospitalization in the
      case described are characteristic of patients with spontaneous bladder rupture
      and warrant a high index of suspicion in order to achieve an early diagnosis.

PMID- 8140679
TI  - Plasminogen activators and plasminogen activator inhibitor 1 in urinary tract
      cancer.
AB  - The plasminogen activation system is considered to play an important role in
      cancer growth and metastasis. Both plasminogen activators (PAs) and their fast
      acting inhibitors are produced in tumor cells and their surrounding tissues. In
      order to clarify the influence of the existence of malignant tumor in urinary
      tract on the systemic fibrinolytic activity, we designed a study in which we
      compared the plasma levels of PAs and their inhibitors between before and after
      radical resection of tumors. Fourteen patients with renal cell carcinoma and 14
      patients with transitional cell carcinoma participated in the study. In both
      groups, plasma levels of tissue-type plasminogen activator and urokinase-type
      plasminogen activator before the operation were higher than those 15 days after
      operation. The plasma level of plasminogen activator inhibitor 1 (PAI-1),
      however, did not change after the operation in the renal cell carcinoma group,
      and it decreased slightly in the transitional cell carcinoma group although it
      was not significant. When these values of the groups with or without metastasis
      were compared to other organs or lymph nodes, the PAI-1 level before operation
      was significantly higher in the group with metastasis than that without
      metastasis. In the three groups divided by the degree of atypia, PAI-1 level in
      the most atypical group was the highest. These results suggest that the
      fibrinolytic system in the plasma of cancer patients may play an important role
      in tumor growth and metastasis.

PMID- 8140680
TI  - Primary repair of colorenocutaneous fistula in patients with genitourinary
      tuberculosis.
AB  - Two cases of colorenocutaneous fistula due to genitourinary tuberculosis are
      presented. They were successfully managed by single-stage surgery
      (nephroureterectomy, fistulectomy, and primary repair of the colon) and
      antitubercular treatment. The literature is briefly reviewed.

PMID- 8140681
TI  - Seminal vesicle abscess: two case reports and a review of the literature.
AB  - Two new cases of seminal vesicle abscess diagnosed by computerized tomography and
      treated with percutaneous drainage are reported. A review of the 8 cases
      published so far is also presented.

PMID- 8140682
TI  - Carcinoma of the prostate in young patients: a report of two cases.
AB  - Carcinoma of the prostate is rare in young patients and has an aggressive
      biological behavior and rapidly fatal outcome, irrespective of the treatment
      modality. Presentation and clinical course of the carcinoma in 2 patients 28 and
      31 years of age are described with a brief review of the relevant literature.

PMID- 8140683
TI  - Malignant priapism in a patient with metastatic prostate adenocarcinoma.
AB  - Metastases to the penis due to a primary carcinoma of the prostate are rare. In
      approximately half of the patients, malignant priapism is the main symptom. This
      study reports on a case of malignant priapism, caused by a direct and metastatic
      infiltration of the corpora cavernosa by a prostatic adenocarcinoma. Sonography
      gave hints, the magnetic resonance imaging verified the infiltration and
      aspiration cytology verified the carcinoma. Hemodynamics, evaluated by Doppler
      sonography, and intracavernosal blood gas analysis demonstrated a mixed high-low
      priapism without need of therapy.

PMID- 8140684
TI  - Youssef's syndrome: an appraisal of hormonal treatment.
AB  - Two cases of vesicouterine fistula, caused by lower-segment cesarean section, are
      presented. Both cases had classical symptoms of Youssef's syndrome, i.e. cyclic
      hematuria, absence of vaginal bleeding and complete urinary continence. These
      patients were treated by the continuous administration of an estrogen-progestogen
      combination for 6 months. However, it failed in 1 case requiring transabdominal
      transperitoneal closure of the fistula with an interposition of omentum. We feel
      that hormonal treatment may be tried as first modality in the treatment of
      Youssef's syndrome, before resorting to surgery.

PMID- 8140685
TI  - Extrarenal retroperitoneal angiomyolipoma.
AB  - The clinical and pathological findings in a patient with extrarenal
      angiomyolipoma arising in the perinephric space are presented. This location has
      been reported only rarely and sets forth some diagnostic and therapeutic
      difficulties that are also discussed.

PMID- 8140687
TI  - Members. American Ophthalmological Society.

PMID- 8140686
TI  - Epidermal growth factor concentrations in seminal plasma from patients with
      hypogonadism--changes after hormone replacement.
AB  - Epidermal growth factor (EGF) content in seminal plasma of 17 patients with
      androgen deficiency (12 Klinefelter's syndrome and 5 hypogonadotropic
      hypogonadism) was determined before and after hormone replacement. No significant
      increase of plasma testosterone level was demonstrated after testosterone
      administration in Klinefelter's syndrome, although the level in 4 of 5 patients
      with hypogonadotropic hypogonadism reached the normal range. In 16 patients,
      except 1 with hypogonadotropic hypogonadism with no increase of blood
      testosterone level, prostate volume increased after hormone therapy, and volumes
      after treatment were significantly larger than those before treatment. On the
      other hand, EGF concentration in seminal plasma remained at the pretreatment
      level in most patients. It is therefore concluded that although the prostate
      volume increases to almost normal after treatment, prostate function does not
      improve in most patients, indicating that in patients with hypogonadotropic
      hypogonadism fertility potential may remain low, even if they obtain normal
      seminal parameters after treatment.

PMID- 8140688
TI  - Trabeculectomy with releasable sutures.
AB  - We attempted to reduce some of the postoperative complications of trabeculectomy
      by using releasable scleral flap sutures. This technique allows an initial tight
      closure of the scleral flap with the option to increase aqueous humor outflow in
      the early postoperative period. We reviewed our experience with trabeculectomy
      and releasable sutures in 146 eyes (134 patients) and compared these cases with a
      prior series of 128 eyes (124 patients) that underwent trabeculectomy with
      permanent scleral flap sutures. In the control group, 42 eyes (32.8%) had
      clinically detectable shallowing of the anterior chamber in the postoperative
      period. In contrast, shallow anterior chamber was noted in 21 eyes (14.4%) in the
      group with releasable sutures (P = .0003). Flat anterior chamber, defined as
      iridocorneal touch to the pupil margin, occurred in 11 control eyes (8.6%) but in
      only 2 eyes (1.4%) with releasable sutures (P = .0078). Surgical intervention to
      drain suprachoroidal fluid and re-form the anterior chamber was required in eight
      control eyes (6.2%) but in only one study eye (0.7%) (P = .014). At 1 year of
      follow-up, the two groups were similar in terms of mean intraocular pressure, the
      need for ocular hypotensive medications, and failure rate.

PMID- 8140689
TI  - Is observation really appropriate for small choroidal melanomas.
AB  - Many, if not most, patients with a suspected small choroidal melanoma are
      currently managed by observation until tumor enlargement is documented. Current
      evidence appears to be insufficient to determine the correctness of this
      approach. A randomized clinical trial that could resolve this issue is probably
      not feasible. In the absence of satisfactory evidence, the decision about how to
      manage such patients depends on a subjective benefit-risk analysis that takes
      into account two competing but indeterminate risks: the risk of inadequate
      treatment for those patients who have a true melanoma and the risk of excessive
      treatment for those who have a benign nevus. Technologic advances and development
      of effective treatment for metastatic disease may eliminate most of the concern
      that currently accompanies observation as management for such tumors in the
      future.

PMID- 8140690
TI  - Lack of complications of the hydroxyapatite orbital implant in 250 consecutive
      cases.
AB  - The coral-derived hydroxyapatite sphere is a popular, new integrated orbital
      implant designed to provide improved motility of the ocular prosthesis following
      enucleation. Although the implant has rapidly become widely used by
      ophthalmologists, there is little information available regarding the
      complications of this technique in a large series of cases. We report our results
      on our initial 250 consecutive cases of hydroxyapatite implantation for eyes
      enucleated primarily for intraocular neoplasms, with specific emphasis on the
      complication an their management. The reasons for enucleation included uveal
      melanoma (157 cases), retinoblastoma (70 cases), blind painful eye (22 cases),
      and intraocular medulloepithelioma (1 case). Prior treatment to the eye was
      performed before enucleation in 47 cases and included repair of ruptured globe
      (17 cases), plaque radiotherapy (18 cases), external beam radiotherapy (6 cases),
      and others (6 cases). During a mean of 23 months follow-up (range, 6 to 42
      months), there have been no recognizable cases of orbital hemorrhage related to
      the implant and no cases of implant extrusion or implant migration. There was one
      case of presumed orbital infection (culture-negative) that resolved with
      intravenous antibiotics, and the implant was retained within the orbit. Other
      problems included conjunctival thinning in eight cases managed by observation and
      prosthesis adjustment and conjunctival erosion in four cases managed by
      combinations of scleral patch graft, conjunctival flap, and prosthesis
      adjustment. The conjunctival erosion was caused by a poorly fitting prosthesis in
      three cases and wound dehiscence in one case. The complication rate in eyes
      receiving prior radiotherapy or surgery was not increased. The hydroxyapatite
      integrated orbital implant is a well-tolerated motility implant without the high
      rate of extrusion and infection seen with other motility implants.

PMID- 8140691
TI  - Current transitions in ophthalmic aspects of licensure for motor vehicle drivers:
      problems, hazards, and working solutions.

PMID- 8140692
TI  - Blood pressure, hypertension and retinopathy in a population.
AB  - This study provides precise estimates of the prevalence of retinal lesions in
      nondiabetic persons with and without hypertension. The findings suggest that
      retinopathy (6% in normotensives and 11% in people with hypertension), and
      retinal arteriolar narrowing (11% in normotensives and 19% in people with
      hypertension) are common. Further longitudinal study is necessary to evaluate the
      public health significance of these findings.

PMID- 8140693
TI  - Outcomes of surgical and nonsurgical management of nonarteritic ischemic optic
      neuropathy.

PMID- 8140694
TI  - The influence of primary open-angle glaucoma upon the retrobulbar circulation:
      baseline, postoperative and reproducibility analysis.
AB  - CDI is showing continued promise as a reliable, reproducible method to assess the
      hemodynamics of a variety of ophthalmic diseases in which vascular perfusion
      abnormalities are suspect. Moreover, some patients with advanced POAG appears to
      have abnormalities of the vasculature of the retrobulbar circulation that is
      corrected by trabeculectomy. Continued CDI clinical correlations with
      longitudinal studies are now required to elucidate the significance of this
      technology and these results for individual patients.

PMID- 8140695
TI  - Aplasia of the optic nerve.

PMID- 8140697
TI  - Visual function in children with congenital sensorineural deafness.

PMID- 8140696
TI  - The twelfth Frederick H. Verhoeff Lecture: gene sharing in the visual system.

PMID- 8140698
TI  - Transient disappearance of a symptomatic macular hyperfluorescent lesion
      following vitrectomy: a case report.
AB  - We have presented a case of symptomatic macular fluorescence of a presumed
      vascular etiology that transiently disappeared post vitrectomy. Laser
      photocoagulation to the involved area resulted in a good visual outcome. We
      propose that the transient improvement in the fluorescein leakage represented a
      temporary alteration of cellular metabolism, or vascular perfusion, attributable
      to the perfusion solution. We suggest that additional studies are indicated to
      further explore this phenomenon and its potential clinical applicability.

PMID- 8140699
TI  - Topical fibronectin therapy of persistent corneal epithelial defects. Fibronectin
      Study Group.

PMID- 8140700
TI  - Vancomycin in corneal transplantation.

PMID- 8140701
TI  - A new theory of human accommodation: cilio-zonular compression of the lens
      equator.

PMID- 8140702
TI  - Systematic literature review for clinical practice guideline development.
AB  - The purpose of this paper was to evaluate the quality and scope of the published
      literature on functional impairment due to cataract in adults as reviewed for the
      Agency for Health Care Policy and Research Clinical Practice Guideline. We
      examined the method of literature retrieved and analysis performed in the course
      of development of literature-based recommendations for the guideline panel. To
      collect data, we reviewed the process of literature acquisition and
      identification and the quality assessments made by reviewers of 14 individual
      topics composed of 77 issues related to the guideline. We collated this
      information to provide an assessment of the quality and scope of the relevant
      literature. Less than 4% (310) of the approximately 8,000 articles initially
      identified as potentially relevant to the guideline were ultimately used. The
      majority covered three topics (surgery and complication, 100; Nd:YAG capsulotomy,
      77; and potential vision testing, 40). Three other topics--indications for
      surgery, preoperative medical evaluation, and rehabilitation--were devoid of
      articles meeting inclusion criteria. For 43 issues, there was no identifiable
      relevant literature. With few exceptions, the quality of the literature was rated
      fair to poor owing to major flaws in experimental design. Case series (256
      reports) of one type or another accounted for the majority of the included
      literature. There were 17 random controlled trials. This review revealed a sparse
      and generally low-quality literature relevant to the management of functional
      impairment due to cataract, despite a relatively large data base in reputable
      peer-reviewed journals.

PMID- 8140703
TI  - Age as a factor in the bacteriology and response to treatment of subperiosteal
      abscess of the orbit.
AB  - The clinical course of SPA of the orbit is associated with the age of the
      patient. That association might be explained through a series of intermediate
      relationships: the clinical course correlates with the bacterial constituency,
      the bacterial constituency is related to physiologic derangement within the
      sinuses, the physiologic derangement may vary with the degree of obstruction of
      the sinus ostia, and the ostial caliber relative to the volume of the cavity that
      must be drained decreases with patient age into late adolescence. The controversy
      between pediatricians and surgeons over the appropriate indications for drainage
      might be resolved with the acknowledgement that each side is correct on the basis
      of the patient populations treated. It is hoped that recognition of the age
      related variations in SPA will permit a more systematic approach to the
      management of this complex infectious disease.

PMID- 8140704
TI  - Lens opacities in women in Beaver Dam, Wisconsin: is there evidence of an effect
      of sex hormones?
AB  - Analyses reported here suggest a protective effect of estrogen status on lens
      opacities, which are very common in adult Americans. Clinical trials are
      currently underway to assess protective effects of past menopausal estrogens on
      other disease. Evaluation of lenses of the participants would shed light on
      effects in the lens.

PMID- 8140705
TI  - Experimental and clinical observations on massive suprachoroidal hemorrhage.
AB  - We have been able to create a reproducible experimental model of nonexpulsive
      massive suprachoroidal hemorrhage in a rabbit eye. Massive suprachoroidal
      hemorrhage was demonstrated on echography and confirmed on histopathologic
      examination in all eyes. The natural course of the disease suggests that there is
      very little change in the size of the choroidal detachment in the first 7 days.
      Maximum liquefaction of the suprachoroidal hemorrhage clot was seen to occur
      between 7 and 14 days. However, increased retinal and ciliary body atrophy was
      also noted at 14 days. Therefore, the optimum time to drain massive
      suprachoroidal hemorrhage appears to be between 7 and 14 days. Immediate
      sclerotomy during the acute formation of massive suprachoroidal hemorrhage
      resulted in further increase in the suprachoroidal hemorrhage, with marked
      extension of the hemorrhage into the retina and vitreous. Therefore, in our
      opinion, immediate sclerotomy during massive suprachoroidal hemorrhage is
      detrimental to the eye. Our clinical data have shown that eyes with massive
      suprachoroidal hemorrhage can be treated successfully by secondary surgery, and
      the majority of the eyes can be salvaged with good visual results. No serious
      complications of this surgery were encountered in our cases. We advocate early
      surgical intervention between 7 and 14 days. Aggressive anterior and posterior
      segment reconstruction by anterior and posterior vitrectomy after sclerotomy
      drainage of the suprachoroidal hemorrhage is essential for better anatomic and
      visual results. Our animal data and clinical experience suggest that the optimum
      time of drainage of massive suprachoroidal hemorrhage is between 7 and 14 days.
      The results of our animal experiments in relation to human clinical application
      should be taken with caution. Furthermore, we had a small number of animals to
      study the various groups. In addition, longer follow-up may be needed for
      comparing controls with the treatment groups. Our animal model may help in such
      future studies on massive suprachoroidal hemorrhage.

PMID- 8140706
TI  - Antimicrobial pharmacokinetics in endophthalmitis treatment: studies of
      ceftazidime.
AB  - Ceftazidime has pharmacokinetic advantages for treatment of endophthalmitis
      caused by gram negative-organisms by intravenous administration. Additionally,
      its spectrum of coverage for these organisms and its relatively low toxicity
      after intraocular injection are favorable attributes. These studies demonstrate
      that inflammation leads to a significant reduction of the blood-ocular barriers
      to ceftazidime. This increased permeability shortens the half-life of the drug
      after intraocular injection but allows a significant penetration into the eye
      after a single intravenous dose so that therapeutic levels are achieved.
      Ceftazidime appears to be removed by both the anterior and the posterior route
      without active transport. The experiments demonstrate the importance of the
      vitreous as a barrier to achieving significant concentration of antibiotic within
      the eye after intravenous administration and confirm the importance of the
      vitreous in prolonging the half-life of drugs injected intravitreally. Finally
      the results emphasize that the pharmacokinetic behavior of drugs for treatment of
      endophthalmitis must be assessed in inflamed eyes both with and without intact
      vitreous, since these factors play a large role in drug availability and
      concentration in the vitreous cavity and are the major variables in the clinical
      setting.

PMID- 8140707
TI  - Treatment of thyroid ocular myopathy with adjustable and nonadjustable suture
      strabismus surgery.
AB  - Our results pooled with those of others demonstrate a statistically significant
      improvement in outcome when adjustable sutures are implemented in the treatment
      of thyroid ocular myopathy. To our knowledge, this degree of significance has not
      been reported previously. We believe the value of adjustable suture strabismus
      surgery lies mainly in the prevention of large undercorrections and
      overcorrections. However, one cannot guarantee fusion or long-term alignment
      stability, especially without prism use. A randomized, prospective, controlled
      study to compare the nonadjustable and adjustable techniques for the treatment of
      thyroid ocular myopathy has yet to be performed. The success of any type of
      strabismus surgery relies on many factors. Future endeavors should implement the
      quantified adjustable suture technique to better define how preoperative
      conditions influence the response to strabismus surgery in Graves' patients.

PMID- 8140708
TI  - Photopic ON- and OFF-pathway abnormalities in retinal dystrophies.

PMID- 8140710
TI  - Mycoplasma-like organisms and ophthalmic disease.

PMID- 8140711
TI  - Periocular xanthogranulomas associated with severe adult-onset asthma.
AB  - This article describes six patients who presented, usually bilaterally, with
      yellow-orange, elevated, indurated, and nonulcerated xanthomatous eyelid lesions,
      typically extending into the anterior orbital fat, and sometimes involving the
      extraocular muscles and the lacrimal gland. Because the eyelids remained intact
      and because the process did not reach the deep orbital and perioptic connective
      tissues, visual acuity was well preserved. There is cosmetic morbidity and
      occasionally motility restriction with advancing involvement of the extraocular
      muscles. All patients had variably severe adult-onset asthma that required
      treatment with systemic prednisone and inhalants. No evidence of Erdheim-Chester
      disease was found in any patient, but the appearance in one patient, after 25
      years of follow-up, of a separate subcutaneous necrobiotic xanthogranulomatous
      lesion in the mandibular region with an associated paraproteinemia, suggests that
      at least some of our cases might be a mild form of necrobiotic xanthogranuloma.
      For this reason, we would suggest repeated periodic serum protein
      immunoelectrophoretic studies as well as evaluation for lymphoma. Therapy
      probably should consist of low doses of periorbital radiotherapy coupled with
      high doses of corticosteroids. Should this not be successful, then systemic
      administration of corticosteroids with chemotherapeutic agents might be
      efficacious, as in necrobiotic xanthogranuloma.

PMID- 8140712
TI  - Chlamydiosis in mariculture-reared green sea turtles (Chelonia mydas).
AB  - From August 1990 to June 1991, a moderate die-off of 4- to 5-year-old green sea
      turtles (Chelonia mydas) occurred at Cayman Turtle Farm, Grand Cayman, British
      West Indies. Clinical signs included lethargy, anorexia, and inability to dive.
      Many of the ill turtles floated on the surface of their tanks. There was no
      apparent sex predilection. Complete necropsies, including histopathologic
      examination of tissues, were performed on eight turtles. Necropsies revealed
      multiple irregular discrete to patchy 1-10 mm pale gray foci throughout the
      hearts of four turtles. By light microscopic examination, the most severe and
      consistent lesions were necrotizing myocarditis, histiocytic to fibrinous
      splenitis, and hepatic lipidosis and necrosis. A mixed leukocytic infiltrate of
      acidophils, macrophages, and lymphocytes was present in affected areas of the
      heart. Other lesions included lymphocytic/plasmacytic interstitial nephritis,
      subacute interstitial pneumonia, subacute mesenteric vasculitis, chronic/active
      enteritis of the small intestine, and occasional granulomas associated with
      spirorchid trematode ova. Chlamydiae could be demonstrated in macrophages in
      sections of paraffin-embedded heart, liver, and spleen and in myocardial fibers
      and hepatocytes using a modified Macchiavello's stain. Chlamydial antigen was
      detected by light microscopic examination in the cytoplasm of myocardial fibers
      and in occasional hepatocytes using a commercially available genus-specific
      antichlamydial monoclonal antibody and the avidin biotin peroxidase complex
      staining method. Electron microscopic examination of the heart of the most
      severely affected turtle revealed developmental stages of chlamydial organisms. A
      suspension of heart from this turtle was inoculated into the yolk sacs of chicken
      embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140713
TI  - The gamma delta T cell population in sheep experimentally infected with bovine
      leukemia virus.

PMID- 8140709
TI  - Factors affecting the efficacy of antibiotics in the treatment of experimental
      postoperative endophthalmitis.

PMID- 8140714
TI  - Granular cell basal cell tumor of the eyelid in an F344 rat.

PMID- 8140715
TI  - Pathology of eastern equine encephalitis in emus (Dromaius novaehollandiae).

PMID- 8140716
TI  - Uremic encephalopathy in a horse.

PMID- 8140717
TI  - Urethral atresia with uroperitoneum in a newborn bovine freemartin.

PMID- 8140718
TI  - Zygomycosis caused by Conidiobolus coronatus in a llama (Lama glama).

PMID- 8140719
TI  - Disseminated protothecosis caused by Prototheca zopfii in a cow.

PMID- 8140720
TI  - Postvaccinal sarcomas in the cat: histology and immunohistochemistry.

PMID- 8140721
TI  - Acquired equine motor neuron disease.

PMID- 8140722
TI  - Comparative histopathology of pemphigus foliaceus and superficial folliculitis in
      the dog.
AB  - A comparative histopathologic study of 50 cases of pemphigus foliaceus and 47
      cases of superficial folliculitis in the dog was undertaken to identify those
      histopathologic features important in differentiating these diseases. All cases
      were diagnosed by the Surgical Pathology Service of the Laboratory of Pathology
      of the University of Pennsylvania, School of Veterinary Medicine, between January
      1986 and March 1991. These cases were followed clinically to determine the
      accuracy of the initial histopathologic diagnosis. Data were analyzed by Fisher's
      exact test for discrete data and the Mann-Whitney U-test for continuous data. A
      probability of < 0.05 was considered statistically significant. The following
      breeds were affected with pemphigus foliaceus: Akita, Brittany Spaniel, Chow
      Chow, Collie, Dachshund, Doberman Pinscher, English Cocker Spaniel, English
      Setter, Golden Retriever, Siberian Husky, Laborador Retriever, Miniature
      Schnauzer, Old English Sheepdog, Scottish Terrier, Chinese Shar Pei, Spitz,
      Shetland Sheep Dog, Weimeraner, and West Highland White Terrier. An increased
      risk of developing pemphigus foliaceus was noted in the Akita (OR = 37.8),
      English Springer Spaniel (OR = 20.7), Chow Chow (OR = 12.3), Chinese Shar Pei (OR
      = 7.9), and Collie (OR = 3.9). Pemphigus foliaceus had a higher average density
      of acantholytic cells (226 +/- 22.9) than superficial folliculitis (11.8 +/-
      4.6), and acantholytic cells were 183 times more likely to be present in
      pemphigus foliaceus. The presence of rafts of acantholytic cells occurred in
      pemphigus foliaceus (23/50) more often than superficial folliculitis (1/47).
      Recornification and reformation of pustules were, respectively, 13.4 and 3.6
      times more likely to occur in pemphigus foliaceus.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8140723
TI  - Gastrointestinal aspergillosis and zygomycosis of cattle.
AB  - Gastrointestinal mycosis was diagnosed in 73 lesions of 32 cattle without a
      history of engorgement, and tissues of 29 animals were examined
      histopathologically. The omasum was the target organ for infection, followed by
      the rumen and reticulum. Acute necrohemorrhagic lesions dominated, with
      infiltration of neutrophils and thrombosis. The etiologic diagnosis was
      accomplished by indirect immunohistochemical staining of fungal elements with a
      panel of mono- and polyclonal antibodies raised against fungal antigens.
      Aspergillosis and zygomycosis were diagnosed in one or more organs of 11 (34.4%)
      and 20 (62.5%) cattle, respectively, and dual infections were found in three
      lesions of two animals. Candidosis was diagnosed in only one case. Hematogenous
      spread of fungi predominantly to the liver was seen in nine animals. Lymphogenic
      spread of aspergilli to mesenteric and omasal lymph nodes occurred in one and two
      animals, respectively. Factors that seemed to predispose to mycotic infection
      included presence of other diseases and intense antimicrobial therapy. These
      factors and post-partum status, which included 23 of 29 (79.3%) cows, predisposed
      to mycosis in several ways, e.g., reflux of acidic abomasal contents into the
      forestomachs, stasis of proventricular content, metabolic dysfunctions, and
      stress.

PMID- 8140724
TI  - Primary mesenchymal (nonangiomatous/nonlymphomatous) neoplasms occurring in the
      canine spleen: anatomic classification, immunohistochemistry, and mitotic
      activity correlated with patient survival.
AB  - Surgical submissions from canine splenectomy cases spanning a 3-year period (1988
      1990) were evaluated. Eighty seven neoplasms of the spleen considered to be of
      nonangiomatous and nonlymphomatous origin were selected for morphologic
      classification, mitotic index determination, immunohistochemical analysis, and
      patient survival determination. In 76/87 cases, patient survival information was
      available, and the mitotic index was determined in 83/87 cases.
      Immunohistochemistry for selected antigens (vimentin, desmin, smooth muscle
      actin, myosin, and factor VIII-related antigen) was performed in 58/87 of the
      cases. Morphologic classification of these lesions in standard HE preparations
      yielded the following neoplastic groups: fibrosarcoma (19/87), undifferentiated
      sarcoma (19/87), leiomyosarcoma (14/87), osteosarcoma (8/87), mesenchymoma
      (7/87), myxosarcoma (6/87), histiocytic sarcoma (6/87), leiomyoma (3/87), lipoma
      myelolipoma (2/87), liposarcoma (2/87), and malignant fibrous histiocytoma
      (1/87). A lack of distinct morphologic characteristics among many of the
      neoplasms that were classified as either fibrosarcoma, leiomyosarcoma, or
      undifferentiated sarcoma contrasted these groups with the relatively unambiguous
      features that distinguished the other sarcoma groups. Using immunohistochemical
      staining for muscle-specific antigens (desmin, smooth muscle actin, and myosin),
      specific staining often overlapped extensively within the neoplastic groups of
      fibrosarcomas, leiomyosarcomas, and undifferentiated sarcomas, suggesting either
      ambiguous morphologic findings or the possibility of a common histogenesis from
      smooth muscle trabeculae or a distinct population of splenic myofibroblasts. The
      biological behavior of all tumors examined could be placed into three categories
      of patient survival: (1) benign, noninvasive tumors (leiomyoma, lipoma) with
      prolonged survival intervals; (2) malignant tumors (fibrosarcoma,
      undifferentiated sarcoma, leiomyosarcoma, osteosarcoma, myxosarcoma, histiocytic
      sarcoma, and liposarcoma), showing severely truncated survival (median 4 months
      with 80-100% mortality after 12 months; and (3) intermediate survival periods
      (median 12 months with 50% 1 year survival) attributed to a single group of
      neoplasm, the mesenchymomas. The biological behavior of primary splenic
      nonangiomatous, nonlymphomatous sarcomas was most closely correlated with
      observed mitotic index. Splenic neoplasms of this type with a mitotic index < 9
      showed significantly (P < 0.0001) longer survival intervals than those with an
      index > 9. With the exception of osteosarcoma, all anatomically defined tumor
      groups contained one or more specimens with a mitotic index < 9. The clinical
      prognosis given for splenic sarcomas should be modified according to the mitotic
      index as a predictive value for patient survival.

PMID- 8140725
TI  - Juvenile-onset neuronal ceroid-lipofuscinosis in Rambouillet sheep.
AB  - Two, 8-month-old Rambouillet half-sister ewes with signs of visual loss and
      decreased mentation were examined. Ewe No. 1 was necropsied at 10 months of age,
      and after being held under observation for a further 6 months, ewe No. 2 was
      necropsied at 16 months of age. At that time, the ewe was blind and severely
      depressed. Both ewes had deposition of an autofluorescent lipopigment, identified
      as ceroid-lipofuscin, in neurons of the brain, spinal cord, eye, and dorsal root
      ganglia. The disease process was progressive and characterized by deposition of
      lipopigment with neuronal degeneration and severe fibrillary astrogliosis. This
      progressive loss of neurons in the older ewe led to severe retinal degeneration.
      No pigment was observed in cells outside of the nervous system and eye.
      Controlled breeding studies have shown that this disease has an autosomal,
      recessive inheritance. The disease referred to here as juvenile-onset neuronal
      ceroid-lipofuscinosis of Rambouillet sheep is unlike the majority of the
      hereditary ceroid-lipofuscinoses that occur in human beings and animals in that
      only the nervous system is affected. Therefore, this disease could serve as an
      excellent model for the study of lipopigment deposition that affects the nervous
      system as a result of various disease states and during aging.

PMID- 8140726
TI  - Tissue factor expression in bovine endothelial cells induced by Pasteurella
      haemolytica lipopolysaccharide and interleukin-1.
AB  - Pasteurella haemolytica in cattle produces fibrino-hemorrhagic pleuropneumonia
      characterized by extensive pulmonary microvascular thrombosis and parenchymal
      necrosis. The purpose of this in vitro study was to determine if P. haemolytica
      lipopolysaccharide (LPS) promotes vascular thrombosis by inducing a procoagulant
      state in vascular endothelial cells. After treatment of confluent monolayers of
      bovine pulmonary artery endothelial cells with various concentrations of either
      P. haemolytica LPS or Escherichia coli LPS, the procoagulant activity of the
      endothelial cells was determined using a chromogenic assay dependent on cellular
      tissue factor expression. The LPS treatment induced significant increases in
      cellular tissue factor expression in a LPS concentration- and time-dependent
      manner. Highest levels of tissue factor were present at 22 hours after treatment,
      although high LPS concentrations induced moderate tissue factor levels at 5 hours
      after treatment. Interleukin-1 also induced tissue factor expression in
      endothelial cells and enhanced the LPS-induced effects. This interleukin-1 effect
      could be diminished by concurrent use of an interleukin-1 receptor antagonist.
      These results demonstrate that LPS and cytokine promotion of a procoagulant state
      in endothelial cells occurs in vitro. Similar mechanisms may play a role in P.
      haemolytica-mediated pulmonary vascular thrombosis.

PMID- 8140727
TI  - In vitro and in vivo activity of human interleukin-8 in dogs.
AB  - Interleukin-8 (IL-8), a proinflammatory cytokine produced by human monocytes,
      fibroblasts, and endothelial and epithelial cells, is effective not only on cells
      and tissues of human beings but also on those of several animal species. We
      investigated the importance of recombinant human IL-8 for the activation of
      canine neutrophils in vitro and its potential for inducing inflammation in vivo.
      Shape change (10(-9)-10(-7) M IL-8) and chemotaxis (10(-10)-10(-6) M IL-8) assays
      were used to determine the activation of canine neutrophils in vitro. Chemotaxis
      was induced by IL-8 at doses > 10(-8) M with a maximum response at 10(-6) M. A
      rapid shape change of comparable intensity was elicited by 10(-9)-10(-7) M IL-8.
      Thirty minutes after intradermal injection of 10(-9) moles of IL-8, emigration of
      neutrophils could be observed and became more intense at 60 minutes and 240
      minutes, respectively. Zymosan-activated canine plasma, which served as a
      positive control, induced a rapid, massive, and more diffuse neutrophil
      accumulation, whereas the reaction after IL-8 was weaker but still significant.
      The neutrophil accumulation after IL-8 was preferentially located in perivenular
      areas of the deep dermis. Recombinant human IL-8 is capable of activating canine
      neutrophils in vitro and is able to generate significant neutrophil accumulation
      in dog skin. Its activity is lower than that in human, rabbit, and rat systems.

PMID- 8140728
TI  - Signs and lesions of experimental Sendai virus infection in two genetically
      distinct strains of SCID/beige mice.
AB  - The pathogenesis of Sendai virus infection was studied in genetically
      immunodeficient mice of genotype scid/scid.bg/bg (SCID-beige) using C.B-17 SCID
      beige mice, a BALB/c-related strain that expresses the same major
      histocompatibility complex as the Sendai virus-susceptible DBA/2 (H-2d). Mice
      were inoculated intranasally with isolate 771076 of Sendai virus, then killed at
      2-day intervals beginning on day 4 post-inoculation. Clinical signs were evident
      beginning at 8 to 10 days post-inoculation, and all animals remaining were killed
      in extremis by 14 to 17 days post-inoculation. Lesions in inoculated mice were
      confined to the respiratory tract. In the nasal passages, a nonresolving
      rhinitis, with epithelial hyperplasia/metaplasia occurred. Cranioventral
      bronchopneumonitis was characterized by marked hyperplasia and necrosis of
      epithelial cells lining airways and with leukocytic infiltration. At the alveolar
      level, there was marked hypertrophy and hyperplasia of type II pneumocytes,
      mobilization of alveolar macrophages, and obliteration of the normal architecture
      in severely affected areas. Viral antigen was evident beginning at 4 days post
      inoculation and persisted in affected areas throughout the duration of the study.
      Because immunocompetent C57BL/6 mice are known to be genetically resistant to
      Sendai virus, the susceptibility of C57BL/6 SCID-beige to Sendai virus was then
      compared to that of C.B-17 SCID-beige mice. In age-matched animals of the two
      strains, there was no evidence of natural resistance to Sendai virus infection in
      the immunodeficient C57BL/6 strain compared to the C.B-17 mice. These studies
      indicate that the genetic differences in susceptibility of two strains of
      immunocompetent mice to Sendai virus infection are eliminated by expression of
      the mutations scid and beige.

PMID- 8140729
TI  - Morphogenesis of enteric lesions induced by group D rotavirus in ringneck
      pheasant chicks (Phasianus colchicus).
AB  - Eight day-old male and female ringneck pheasants (Phasianus colchicus) were
      inoculated with group D rotavirus and necropsied at 4, 7, and 11 days post
      inoculation. The intestinal tracts were examined by light and electron
      microscopic and immunohistochemical methods. By 4 days post-inoculation, 2/3
      (66%) inoculated birds were stunted and had diarrhea and dilated intestines.
      Intestinal villi were shortened, and many villous enterocytes were partially
      detached from the lamina propria. Crypts were hyperplastic, and the lamina
      propria contained a diffuse infiltrate of lymphocytes, plasma cells, and
      macrophages. Immunoreactivity to rotaviral antigen was localized to enterocytes
      on the tips of villi in the duodenum, jejunum, and proximal ileum. By 7 days post
      inoculation, 3/3 (100%) inoculated birds had clinical signs and gross and
      microscopic changes similar to those at 4 days post-inoculation but more severe.
      Immunoreactivity was localized in enterocytes scattered along the sides of villi,
      in occasional crypt enterocytes, and within macrophages in the villous lamina
      propria. Ultrastructurally, infected enterocytes contained cytoplasmic aggregates
      of viroplasm with multiple viral core particles. Numerous mature virions (60-75
      nm in diameter) were present within dilated components of the cytocavitary
      network. Macrophages within the lamina propria contained phagocytosed remnants of
      necrotic virus-infected cells. By 11 days post-inoculation, birds did not have
      gross lesions, but 1/2 (50%) had mild crypt hyperplasia and an infiltrate of
      leukocytes in the lamina propria. Occasional enterocytes along the sides of villi
      and macrophages in the lamina propria were immunoreactive for viral
      antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140730
TI  - Naturally occurring orocutaneous papillomas and carcinomas of brown bullheads
      (Ictalurus nebulosus) in New York State.
AB  - Ninety-four brown bullheads (Ictalurus nebulosus) with spontaneous orocutaneous
      neoplasms (papillomas and carcinomas) were studied grossly and by light
      microscopy. Of these 94 fish, 71 were selected from 505 fish examined
      macroscopically during field surveys and 23 were selected from those submitted
      for diagnostic study. Fish with neoplasms came from 17 locations throughout New
      York State: Buffalo River, Canaan Lake, Cazenovia Lake, Delta Lake, Fort Pond,
      Greenwood Lake, Hudson River, Lake George, Lake Tiorati, Lincoln Hall Pond.
      Lincoln Pond, Oneida Lake, Onondaga Lake, Rutland Pond, Salmon River, Silver
      Stream Reservoir and Swan Lake. The prevalence varied from 0 to 100%. Multiple
      neoplasms were more common (84/94, 89%) than solitary ones (10/94, 11%). In order
      of decreasing frequency, neoplasms arose on the head, especially the ventral
      aspect, the lower dental plate, the upper dental plate, the trunk, the barbels,
      the fins, the tongue, and the tail. Of the 38/94 brown bullheads (40%) with
      tumors in both upper and lower lips and dental plates, 24/38 (63%) had the tumors
      in opposition. Macroscopically, soft, pink or yellowish papillary masses
      protruded above the normal epithelial surfaces. Histologically, cutaneous and
      oral neoplasms originated from the morphologically similar Malpighian epithelial
      cells of the surface epithelia and from the outer cells of the enamel organ.
      Based on histopathologic criteria, cutaneous and oral neoplasms were considered
      the same disease in different anatomic locations. No apparent difference in
      biologic behavior was noted between cutaneous and oral neoplasms. The lesions
      apparently progressed from benign papilloma to locally invasive carcinoma (28/94,
      30%). Neoplastic emboli were seen in one case, and no metastases were detected.
      There was no statistically significant difference between the susceptibility of
      males (20/57, 35%) and females (6/26, 23%) to carcinomas. An apparent correlation
      was noted between a higher frequency of malignant tumors and longer body size
      (3/13 fish [23%] < 30 cm, 17/54 fish [31%] 30-34 cm, and 7/18 fish [39%] > 34
      cm).

PMID- 8140731
TI  - Genital lesions following long-term administration of clenbuterol in female pigs.
AB  - Pathologic findings, lectin histochemistry, and nuclear estrogen receptors were
      studied in the reproductive organs of gilts treated with clenbuterol. A ration
      containing 1 ppm of clenbuterol was fed for 40 days to four Landrace x Large
      white, 9-month-old gilts, weighing 134 to 172 kg at slaughter (gilt Nos. 5-8).
      Four gilts (Nos. 1-4) served as controls. Treated animals had macroscopic lesions
      characterized by microcystic ovaries and uterine atrophy. Histopathologic lesions
      included atretic degeneration of many ovarian follicles, complete absence of
      functional corpora lutea, a reduction in the number of endometrial glands, and a
      decrease in cytoplasmic volume of endometrial and glandular epithelial cells. In
      ovaries, uterus, and vagina lectin histochemistry, performed with thirteen
      different biotinylated lectins, revealed a different staining distribution
      between control and treated gilts. The binding pattern of Ricinus communis
      agglutinin-I (RCA-I) and -II (RCA-II) in the ovaries of control gilts, displayed
      labeling of cytoplasm in theca interna cells of Graafian follicles. There was no
      labeling of the same cells in treated gilts. Labeling patterns with Griffonia
      simplicifolia agglutinin-I (GS-I), Phaseolus vulgaris agglutinin (PHA), RCA-I and
      RCA-II documented a difference in the vascularity of the theca interna between
      Graafian follicles of control and treated gilts. The GS-I and Ulex europaeus
      agglutinin-I (UEA-I) binding patterns in uterus and vagina of treated gilts when
      compared to control gilts suggested that there was a block of the cycling
      activity in the proliferative stage. Immunohistochemical staining for estrogen
      receptors in the endometrium was positive in all but one treated gilts, and
      negative to weakly positive in control gilts. Serum progesterone concentrations
      were decreased in treated animals when compared to control; estradiol
      concentrations were similar in both group of gilts. Cystic ovaries, uterine
      atrophy, and reduction in progesterone concentrations suggested that clenbuterol
      changed ovarian hormonal activity in treated animals.

PMID- 8140732
TI  - Experimental rabies infection of non-nervous tissues in skunks (Mephitis
      mephitis) and foxes (Vulpes vulpes).
AB  - Non-neural tissues, from three male and four female stripped skunks (Mephitis
      mephitis), 5 to 7 months old, and one male and two female red foxes (Vulpes
      vulpes), 12 to 16 months old, experimentally infected with street rabies virus,
      were examined by light microscopic immunohistochemical and electron microscopic
      methods. This is the first report of ultrastructural lesions in rabies-infected
      adrenal medulla, cornea, and nasal glands. Using the streptavidin biotin
      peroxidase technique, antigen was detected in mucous cells and interstitial
      neurons and their processes in the submandibular salivary gland, in chromaffin
      cells of the adrenal medulla, in epidermal cells of the skin, in external root
      sheath cells of hair follicles, and in corneal epithelial cells. Electron
      microscopically, matrix (viral nucleocapsid), virions, and anomalous viral
      products were common in most tissues examined, but their relative proportions
      varied. The results suggested that replication with minimal accumulation of
      matrix and anomalous viral growth products was characteristic of growth in
      tissues (submandibular salivary gland) that frequently produce high titers of
      virus, whereas replication with large amounts of matrix and anomalous structures
      occurred in tissues (adrenal gland and nasal gland) that generally contained low
      or moderate titers of virus. Novel findings included viral budding into secretory
      granules, increase in microfilaments in infected mucogenic cells, and continuity
      of viral convoluted membranous profiles with rough endoplasmic reticulum of
      chromaffin cells and nasal glandular cells. The presence of viral antigen and
      developing virus in extra-neural tissues constitutes a potential risk of non-bite
      exposure to people in certain groups/occupations.

PMID- 8140733
TI  - Evaluation of fibular head transposition for repair of experimental cranial
      cruciate ligament injury in dogs.
AB  - Unilateral cranial cruciate ligament excision and fibular head transposition
      (FHT) were performed on 30 adult dogs. Vertical ground reaction forces were
      determined using force plate data before and after surgery. Cranial drawer
      motion, tibial rotation, and varus-valgus motion were measured at monthly
      intervals. Radiographic, gross, and histological examinations of the stifle
      joints that had been operated on were performed 3 weeks, 4 months, and 10 months
      after surgery. A scoring system was used to evaluate lameness, osteophyte
      formation, and meniscal damage. Rank correlation coefficients were calculated
      between variables tested in pairs. Cranial drawer motion and abnormal tibial
      rotation were present in all of the joints that had been operated on. Peak
      vertical force and associated impulse were not restored during the study time
      period. Meniscal damage was noted in 25% of the dogs at month 4 and in 50% of the
      dogs at month 10. Progressive gross and histological deterioration of the
      articular cartilage was observed in all joints. Positive correlations were noted
      between the degree of stifle joint instability and meniscal injury or
      radiographic changes. FHT did not control cranial drawer motion and rotational
      instability, was not successful in restoring limb function, and did not prevent
      joint degeneration, especially meniscal damage.

PMID- 8140734
TI  - The effects of plate type, angle of ilial osteotomy, and degree of axial rotation
      on the structural anatomy of the pelvis.
AB  - Unilateral triple pelvic osteotomy was performed with three variations in
      technique on canine cadaver pelves. The following variables were studied: the
      angle of the ilial osteotomy (perpendicular to the long axis of the ilium and 10
      degrees, 20 degrees, and 30 degrees off perpendicular); the degree of axial
      rotation (20 degrees, 30 degrees, and 45 degrees); and the type of fixation
      (canine pelvic osteotomy plate [CPOP] or a 2.7-mm dynamic compression plate
      [DCP]). Structural changes measured were the pelvic inlet and acetabular area,
      interischiatic tuberosity distance, and degree of acetabular version. Means and
      standard error of the means were determined for all pelvic measurements and were
      analyzed by three-way analysis of variance (P < .05). As the axial rotation
      increased from 20 degrees to 45 degrees an ilial osteotomy angled 10 degrees, 20
      degrees, or 30 degrees resulted in a significantly greater decrease in the pelvic
      inlet area and significantly less deviation of the interischiatic tuberosity
      distance and degree of acetabular version from normal than an osteotomy directed
      perpendicular to the long axis of the ilium. Compared with the CPOP, as the axial
      rotation increased from 20 degrees to 45 degrees, the DCP resulted in a
      significantly greater decrease in the pelvic inlet area, an increase in the
      interischiatic tuberosity distance and degree of acetabular version, and less of
      an increase in the acetabular area. The results of this study suggest that to
      maximize dorsal acetabular coverage, while minimizing disruption of normal pelvic
      architecture, a CPOP and an ilial osteotomy angled 10 degrees to 30 degrees are
      preferred for all degrees of axial rotation.

PMID- 8140735
TI  - Flexible external fixation for craniodorsal coxofemoral luxations in dogs.
AB  - An external fixator consisting of two Ellis pins connected by a flexible band was
      developed and evaluated as a treatment for craniodorsal coxofemoral luxations in
      dogs. The technique for closed application of the fixator without injury to the
      coxofemoral joint or sciatic nerve was developed in six dog cadavers. The
      coxofemoral joints were then surgically destabilized and the limbs were
      manipulated through a full range of motion to assess the efficacy of the fixator
      in maintaining joint reduction. The fixator maintained joint reduction and
      stability after a surgically created craniodorsal luxation except when the femur
      was externally rotated 90 degrees. A flexible external fixator was then applied
      unilaterally in four healthy dogs. The dogs tolerated the fixator well and were
      bearing weight on the limb within 2 days after surgery; the range of motion was
      not limited by the fixator. The efficacy of a flexible external fixator in
      maintaining joint reduction after craniodorsal coxofemoral luxation was then
      evaluated in eight large dogs. The right coxofemoral joint in each dog was
      luxated surgically by removal of the dorsal joint capsule and transection of the
      ligament of the head of the femur and deep gluteal muscle. The joint was reduced
      and the fixator pins were applied in a closed fashion. In four dogs, a flexible
      external band was applied to the pins. Luxation did not reccur in these four
      dogs. The bands were not applied initially in four control dogs. Luxation
      occurred in three of the four control dogs within 24 hours of surgery. The joints
      that luxated were reduced and the flexible bands applied. Luxation did not recur
      after the bands were in place. The dogs tolerated the external fixators well,
      were bearing weight within 2 days of surgery, and walking with only minimal
      lameness 5 days after surgery. Luxation of the coxofemoral joints did not occur
      during the 2-week period in which the fixators were in place. The joints remained
      stable 1 week after removal of the fixators, at which time the dogs were
      euthanatized. Necropsy evaluation identified inflammation surrounding the pins
      and fibrous thickening of the dorsal joint capsule. The flexible external
      fixators were applied closed, maintained reduction of the coxofemoral joint after
      replacement of a craniodorsal luxation, and allowed weight bearing and limb usage
      soon after surgery. The flexible external fixator has several advantages over
      other methods of treating craniodorsal coxofemoral luxations. Complications noted
      in this study included pin tract drainage, pin loosening, and disruption of the
      flexible bands.

PMID- 8140736
TI  - Rapid tissue expansion for the development of rotational skin flaps in the distal
      portion of the hindlimb of dogs: an experimental study.
AB  - In phase I, tissue expanders were implanted subcutaneously over the lateral
      crural region of four dogs. The expanders were inflated daily to maintain a
      constant intraluminal pressure for 7 days. All animals tolerated the pressurized
      expanders well. Some animal patient discomfort was associated with repeated
      injections into the subcutaneous filling port. One dog developed a limited area
      of tissue loss and exposure of the expander. Tissue response to the expanders
      included epidermal hyperplasia, dermal collagen compression with early
      fibroplasia, and subcutaneous granulation tissue formation adjacent to the
      expander pocket. In phase II, a second group of four dogs underwent rapid skin
      expansion over 7 days. The pressure applied to the expanding skin was determined
      daily and adjusted to approximate the value reported for capillary pressure in
      the dog. Tissue discoloration occurred in two dogs, suggestive of impaired
      circulation. Skin flaps were developed from expanded skin and rotated over the
      talocrural region. Wound dehiscence occurred along the distal flap margin in
      three phase II dogs. These wounds healed by second intention. Branches of the
      caudal saphenous artery were identified, using angiography, as the primary blood
      supply to the skin flaps.

PMID- 8140737
TI  - The effect of long-term bone plate application for fixation of radial fractures
      in dogs.
AB  - This study was divided into two phases. In the in vitro phase, a stainless steel
      bone plate was applied to the cranial surface of the radius in 14 canine limbs.
      The effect of the presence of a bone plate on bone density analysis using
      radiographic photodensitometry (RP) was evaluated by comparing the density
      measurement of the unplated limb to the density measurement of the plated limb.
      The optical density of the plated bones was 12% greater than that of the unplated
      bones. This information was used as a correction factor for the in vivo study. In
      the in vivo phase, 23 dogs with radial and ulnar fractures were examined for
      complications associated with the long-term application of a stainless steel
      plate applied to the cranial surface of the radius. In 14 dogs, RP analysis was
      used to compare the plated limb with the normal, contralateral limb. No
      significant differences in radial cortical bone density existed between the
      plated limb and the contralateral limb after taking into account the effect a
      bone plate had on photodensitometry readings. There was no significant
      correlation between the change in radial cortical density and the duration of
      bone plate application, suggesting that a steady state between bone loss and bone
      production occurs after long-term plate fixation of the fractured canine radius.
      The majority (87%) of the dogs with a plate applied to the radius greater than 1
      year had normal limb usage when standing, walking, or running.

PMID- 8140738
TI  - En bloc ovariohysterectomy as a treatment for dystocia in dogs and cats.
AB  - En bloc ovariohysterectomy, a technique that involves ovariohysterectomy before
      hysterotomy and removal of the neonates, was performed on 63 animals (37 dogs and
      26 cats). Intraoperative complications were limited to 1 cat that bled
      excessively during surgery and was later found to have a clotting disorder.
      Postoperative complications included anemia that required blood transfusion in 3
      cats, uroperitoneum in 1 dog, and death in 1 cat. The rate of neonatal survival
      (75% for dogs and 42% for cats) was similar to that documented by previous
      studies of medical and surgical management of dystocia. We concluded that en bloc
      ovariohysterectomy is a safe and effective alternative to cesarean section for
      surgical treatment of dystocia in dogs and cats.

PMID- 8140739
TI  - Modified lateral orbitotomy for removal of orbital neoplasms in two dogs.
AB  - A simplified lateral orbitotomy is described that decreases surgical time and
      lessens tissue dissection, yet maintains the exposure to the orbit provided by
      other orbitotomy techniques. The approach involves cutting the orbital ligament,
      incising the temporalis aponeurosis from the dorsal zygomatic arch, making
      parallel zygomatic arch osteotomies, and reflecting the zygomatic arch ventrally.
      Closure of the wound involves wiring the zygomatic arch back into place. This
      orbitotomy procedure provides excellent exposure for removal or biopsy of orbital
      masses. The use of this technique for surgical excision of orbital masses in two
      dogs, one with an adenoma of the third eyelid gland and one with an orbital
      fibrosarcoma, and their subsequent management is described.

PMID- 8140740
TI  - Blood gas sampling errors during exercise.

PMID- 8140741
TI  - Influence of cholinergic blockade on the development of epinephrine-induced
      ventricular arrhythmias in halothane- and isoflurane-anesthetized dogs.
AB  - The arrhythmogenic effects of anesthetic drugs are assessed using the
      arrhythmogenic dose of epinephrine (ADE) model. The purpose of this study was to
      determine the influence of cholinergic blockade (CB) produced by glycopyrrolate
      (G) on ADE in 1.5 minimum alveolar concentration (MAC) halothane (H)- and
      isoflurane (I)-anesthetized dogs. Eight dogs (weighing between 12.5 and 21.5 kg)
      were randomly assigned to four treatment groups (H, HG, I, and IG) and each
      treatment was replicated three times. Anesthesia was induced and maintained with
      H (1.31%, end-tidal [ET]) or I (1.95%, ET) in oxygen. Ventilation was controlled
      (carbon dioxide [PCO2] 35 to 40 mmHg, ET). G was administered 10 minutes before
      ADE determination at a dose of 22 microgram/kg (11 microgram/kg, intravenous [IV]
      and 11 micrograms/kg, intramuscular [IM]). The ADE was determined by IV infusion
      of epinephrine at sequentially increasing rates of 1.0, 2.5, and 5.0
      micrograms/kg/min; and defined as the total dose of epinephrine producing at
      least four ectopic ventricular contractions (EVCs) within 15 seconds during a 3
      minute infusion and up to 1 minute after the end of the infusion. Total dose was
      calculated as the product of infusion rate and time to arrhythmia. Data were
      analyzed using a randomized complete block analysis of variance. When significant
      (P < .05) F values were found a least significant difference test was used to
      compare group means. Values are reported as means +/- standard error. The ADE
      (micrograms/kg) for H, HG, I, and IG were 1.53 +/- 0.08, 3.37 +/- 0.46, 1.61 +/-
      0.21, and > 15.00, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140742
TI  - Butorphanol tartrate for partial reversal of oxymorphone-induced postoperative
      respiratory depression in the dog.
AB  - A randomized, blinded, crossover study was designed to evaluate the respiratory,
      cardiovascular, and behavioral effects of butorphanol given postoperatively to
      oxymorphone-premedicated and surgically stimulated dogs. Nine healthy adult dogs
      were premedicated intramuscularly with atropine (0.04 mg/kg), acepromazine (0.10
      mg/kg), and oxymorphone (0.2 mg/kg). Anesthesia was induced with thiamylal (12
      mg/kg) and maintained with halothane in oxygen. According to the protocol of a
      concurrent study, all dogs had percutaneous endoscopic gastrostomy (PEG) feeding
      tubes placed during the first anesthetic episode and removed during the second
      anesthetic episode. All dogs received postoperatively either butorphanol tartrate
      (0.2 mg/kg) or an isovolumetric dose of saline placebo, both given intravenously.
      Respiratory rate (RR), tidal volume (TV), minute ventilation (MV), end-tidal CO2
      concentration (ETCO2), heart rate (HR), and indirect diastolic (DP), systolic
      (SP) and mean arterial (MAP) blood pressures were measured at times 0, 2, 5, 10,
      20, 40, 80, and 120 minutes after injection. The time from injection of the test
      drug until extubation was recorded. RR, MV, HR, and DP were significantly (P <
      .05) increased, while ETCO2 was significantly decreased, for a minimum of 30
      minutes in butorphanol-treated dogs compared with saline controls. TV, SP, and
      MAP were transiently (< or = 15 minutes) increased in butorphanol-treated dogs
      compared with saline controls. There was no significant difference between the
      times to extubation in the butorphanol-treated dogs versus the saline control
      dogs.

PMID- 8140743
TI  - [Acebutolol in the therapy of mild and moderate hypertension].
AB  - Acebutolol (sectral) is one of the new types of cardioselective beta-blockers
      which has at the same time also qualities of ISA. The author made a 6-month
      clinical study comprising 20 patients, focused on the antihypertensive
      effectiveness and tolerance of the drug. Administration of acebutolol led already
      after two weeks to a significant effect on the systolic and diastolic blood
      pressure and during the period of 1-6-month administration the maximal
      antihypertensive effect was achieved (-29 mm Hg systolic BP, -19 mm Hg diastolic
      BP). 24-hour monitoring of the BP proved antihypertensive effectiveness of
      acebutolol regardless whether the drug was administered in two daily doses or
      only once a day. In the course of the investigation no negative metabolic effects
      of acebutolol were observed.

PMID- 8140744
TI  - [Factors affecting serum lipid levels in patients with type 2 diabetes mellitus].
AB  - Serum lipid concentrations were assessed in 147 type 2 diabetics. The patients
      were divided into different sub-groups in order to follow up different factors
      which could have an impact on serum lipids. The mean total cholesterol
      concentrations were significantly higher in diabetic women as compared with men.
      The authors did not reveal significant differences in lipid concentrations
      between obese and non-obese diabetics. Hypertensive diabetics had higher mean
      total cholesterol levels and LDL-cholesterol levels, as compared with diabetic
      patients without hypertension. Patients using oral antidiabetics had
      significantly higher mean triglyceride levels and lower HDL-cholesterol levels,
      as compared with insulin-treated diabetics. In a multiple stepwise regression
      analysis correlated triglycerides with three independent variables: total
      cholesterol, diastolic blood pressure and inversely with HDL-cholesterol. On the
      other hand, total cholesterol correlated significantly with triglycerides, HDL
      cholesterol and proteinuria/day. To sum up, it may be stated, that the results of
      the present investigation are consistent with Reaven's concept of the syndrome X,
      however the cholesterol concentration is affected also by the proteinuria.

PMID- 8140745
TI  - [Prevalence of bronchial asthma, chronic bronchitis and allergic rhinitis in a
      South Moravian District].
AB  - In a random sample of 648 adults (18-70 years), representing 95,836 people by age
      and sex, the prevalence of the above mentioned diseases was assessed. The chi 2
      test revealed that the sample of examined subjects did not differ significantly
      from the distribution of the population as regards age and sex. The prevalence of
      bronchial asthma was 2.0%, of chronic bronchitis 16.3%, pollen rhinitis 4.5% and
      non-seasonal rhinitis 4.9%. In asthma the immunological type of the disease
      predominated markedly. Bronchial hyperreactivity after inhaled histamine was
      almost five time higher in asthma than in bronchitis (100% and 22.5%).

PMID- 8140746
TI  - [Comparison of basic somatometric characteristics in randomly selected
      populations from Prague and Vsetin].
AB  - In 1991-1992 in the Czech Republic an epidemiological survey was conducted
      focused on prevention of iodine deficiency and the incidence of some
      thyropathies. The authors examined samples of the Prague and Vsetin population
      selected at random. The clinical examination comprised also somatometric
      assessment. In a group of 1,100 subjects from Prague and Vsetin anthropometry of
      basic somatometric characteristics was performed (height, body weight, BMI and
      four skinfolds). From comparison of the two groups ensues that the Vsetin
      population is shorter, as compared with the Prague population, the BMI values are
      significantly higher and so is the percentage of subcutaneous body fat.

PMID- 8140747
TI  - [Factors affecting the vulnerability of the left atrium during rapid
      transesophageal atrial stimulation].
AB  - Atrial fibrillation (AF) is associated with a higher morbidity and mortality
      because of the risk of systemic or pulmonary embolism as well as the negative
      impact on cardiac function. The authors investigate in the submitted paper
      factors influencing the vulnerability of atria during transoesophageal atrial
      stimulation (TESP). The group comprised 68 patients with a sinus rhythm, mean age
      56.9 +/- 17.9 years. Depending on the response to rapid atrial stimulation, the
      patients were divided into three groups. In group I (small disposition to AF)
      they revealed a significantly lower age, the relative thickness of the left
      ventricular wall assessed by echocardiography and the dimension of the left
      atrium, as compared with groups with a medium increased (II) and high disposition
      (III) for AF. In group III hypertonic changes on the fundus were found more
      frequently, as well as anamnestic data on hypertension, diabetes and pathological
      values of the recovery period of the sinoatrial node. At the same time
      significantly lower values of the rate of the E wave were observed and of the
      ratio of amplitudes and E/A integrals from the Doppler record of the mitral
      valve. The weight of the left ventricle and its index by groups increased,
      however the changes did not attain statistical significance. Indicators of left
      ventricular systolic function did not differ. The authors conclude that the main
      independent factors which determine the response to provoked AF by the TESP
      method are the diastolic left ventricular function documented by the Doppler
      method, the diameter of the left atrium, the automation of the SA node. Less
      important factors are left ventricular hypertrophy and age.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8140748
TI  - [A fatal hemorrhagic condition after rodenticide ingestion].
AB  - The authors describe a fatal haemorrhagic condition in a 53-year-old man which
      developed after assumed ingestion of so-called "superwarfarins". Symptoms of
      intoxication with substances of the warfarin type include the sudden development
      of haemorrhagic diathesis, marked prolongation of INR and APTT with persisting
      pathological values of these tests after the usual substitution doses of vitamin
      K1. The fluctuation of INR and APTT values during repeated examinations is also
      striking. In the event of such a coagulation finding it is important to consider
      possible superwarfarin intoxication, even if it is difficult to provide direct
      evidence, as it is not possible to assess the ratio of vitamin K1 and K 1, 2, 3
      epoxide.

PMID- 8140749
TI  - [Treatment of macroscopic hematuria complicating renal biopsy by embolization of
      a branch of the renal artery].
AB  - The authors describe a case of recurrent macroscopic haematuria which developed
      after renal biopsy in a young patient with IgA dominant focal and segmental
      mesangioproliferative glomerulonephritis. As conservative treatment was not
      successful, renal angiography was performed which revealed a false aneurysm of
      the segmental branch of the renal artery at the site of the assumed puncture.
      After selective embolization with gelaspon granules macroscopic haematuria
      receded quickly.

PMID- 8140750
TI  - [Thyrotoxic crisis].
AB  - A thyrotoxic Crisis is an acute or subacute metabolic explosion caused by
      uncontrolled release of tyronines from the thyroid gland (more frequently a
      diffuse thyroid gland) following its injury: strumectomy, administration of a
      therapeutic dose of I131, inflammations, or excessive stimulation (massive
      release of TSIg by stress lympholysis, low iodine doses). Concurrently a massive
      conversion of T4 to T3 in tissues must occur which is enhanced by discontinuation
      of beta-blockers, thyrostatics, synthetic glucocorticoids and administration of
      drugs replacing T4 from the bond to plasma carries (salicylates, sodantone,
      furosemide, barbiturates etc.) during stress. The trigger mechanism of the crisis
      is any severe stress (surgery, accidents, infection, childbirth) and the
      administration of iodine preparations. Their effect depends, however, on the
      dose, period of administration and the functional and morphological state of the
      thyroid gland. Small doses of iodine administered for a short period stimulate
      hormonogenesis, large doses (more than 10 mg/day), on the other hand, block the
      iodine pump, T4 and T3 secretion by the thyroid gland and conversion of T4 to T3
      in tissues. In therapy specific procedures are involved: I. Block of T4, T3
      synthesis and secretion a) ipodate, ioipanoic acid, Lugol's solution i.v. b)
      propycil, methimasol c) in iodine-basedowized goitres perchlorate and lithium II.
      Block of T4 to T3 conversion (iodine preparations, incl. amiodarone, beta
      blockers, propycil, dexamethasone). III. Reduction of hypermetabolism (beta
      blockers, Ca inhibitors) IV. Reduction of free T4 and T3 in blood stream (by
      plasmapheresis, haemoperfusion, haemodialysis) V. General provisions in intensive
      therapy (control of hyperpyrexia, dehydration, hypoxia, supraventricular
      arrhythmia and circulatory decompensation).

PMID- 8140751
TI  - [Quantitative determination of left ventricular size using echocardiography].
AB  - Echocardiography makes it possible to examine the mass of the left ventricle both
      by a two-dimensional and one-dimensional approach. The method of one-dimensional
      echocardiography is simpler and more accurate than two-dimensional
      echocardiography. There are two most frequently used conventions for assessment
      of the thickness of the wall and the diameters of its cavity: 1. the method of
      the American echocardiographic society, 2. the Penn-convention. The latter
      correlates better with left ventricular mass assessed on autopsy. The
      prerequisite for use of one-dimensional echocardiography is that the mass of the
      left ventricle is evenly distributed along the whole circumference. This
      assumption must be assessed in advance by two-dimensional echocardiography and it
      is necessary to eliminate from examinations those patients where the left
      ventricle is geometrically impaired. The authors mention also other limitations
      of one-dimensional echocardiography when used for assessment of left ventricular
      mass. The mass of the left ventricle is an independent risk factor and indicator
      of elevated morbidity and mortality in arterial hypertension and therefore its
      assessment is very important in clinical practice. The authors present their own
      observations of dynamic serial examinations used to assess the mass of the left
      ventricle in a female patient with pheochromocytoma and its total regression
      after radical surgery.

PMID- 8140752
TI  - [The antiphospholipid syndrome].
AB  - The author summarized contemporary findings on anti-phospholipid autoantibodies,
      their different types and probable site of action. This autoimmune phenomenon
      produces some typical clinical symptoms which made it necessary to describe them
      as the so-called anti-phospholipid syndrome. If concurrently some autoimmune
      disease is present, in particular lupus erythematosus , this syndrome is
      considered "secondary". If this is not the case, it is assumed that the "primary
      form" is involved. The author suggests diagnostic criteria and in large groups of
      patients suffering from SLE the true prevalence of different symptoms of this
      syndrome is tested with participation of anti-phospholipid antibodies.

PMID- 8140753
TI  - [Ultrasound in the diagnosis of thromboembolism].
AB  - The authors review the importance of echocardiography and duplex examination of
      the blood vessels of the lower extremities for early diagnosis of thromboembolic
      attacks. Echocardiographic examination rules out other causes of the patient's
      complaints such as myocardial infarction, heart defects, ischaemic heart disease
      and others. The main role of echocardiography is, however, detection of symptoms
      of an acute rise of the blood pressure in the right heart or symptoms of its
      failure. The most valuable symptom is dilatation of the right branch of the
      pulmonary artery and dilatation of the right ventricle found in as many as 75%
      patients. It is also useful to assess by the Doppler method the dextrolateral
      systolic pressure from tricuspidal regurgitation. For pulmonary embolism a
      regurgitation rate of 2.8-3.8 m/s is typical. The correlation coefficient is,
      however, lower than when the dimensions of the right and left ventricle are used.
      Evidence of deep venous thrombosis does not reveal pulmonary embolism but has the
      same therapeutic consequences. Duplex sonography has a 95-100% sensitivity and
      specificity in acute thrombosis. In recurrent thrombosis it is necessary to use a
      combination of the two methods. Concurrent echocardiography and duplex sonography
      of the blood vessels of the lower extremities makes it possible to start prompt
      treatment in 70-80% of the patients. In the remainder for diagnosis of
      thromboembolic attacks other methods must be used.

PMID- 8140754
TI  - [Present status of treatment of opportunistic mycotic infections with systemic
      antimycotics].
AB  - The authors present a brief review of systemic antimycotics available at present,
      incl. indications and treatment. In a table these preparations are compared as
      regards pharmacokinetic properties and undesirable effects.

PMID- 8140755
TI  - [Diagnosis of systemic mycotic infections].
AB  - The diagnosis of mycotic infections still remains a serious problem. The clinical
      picture lacks specific manifestations, usually it does not differ substantially
      from bacterial infections. Routine laboratory examinations are only of subsidiary
      importance and even more specific methods (assessment of antibodies, and in
      particular detection of mycotic antigens) do not meet expectations so far. To
      establish the diagnosis of systemic mycosis it is thus most important to consider
      the possibility and to support clinical suspicion by an aimed examination.

PMID- 8140756
TI  - [Dysfunction of valvular prostheses].
AB  - Implantation of artificial mechanic valvular prostheses significantly improves
      and prolong the life of patients with valvular defects with a haemodynamic
      impact. This therapeutic method does not cure the patients and operation switches
      the problem of a natural dysfunctional valve to that of a functional artificial
      valve with improvement of the quality of life and its prolongation. The long-term
      effect and thus the general prognosis--the patient's "fate" depends above all on
      complications such as infections and haemocoagulation which are the main cause of
      dysfunction of artificial prostheses. The authors describe in the submitted paper
      basic principles of prevention of these undesirable events and decisive steps
      which must be taken to ensure a rapid and accurate diagnosis of imminent of
      already developed dysfunction of the prosthesis and its solution under the given
      conditions.

PMID- 8140757
TI  - [Amyloid light-chain amyloidosis with primary involvement of the
      cardiorespiratory system--2 case reports].
AB  - The authors describe the cases of two women suffering from AL amyloidosis with
      affection of the heart muscle in particular. In one of the patients there were
      also massive amyloid deposits in the lungs which is an exceptional finding. The
      observations confirm the adverse prognosis of amyloidosis, the rapid progression
      of the disease after the onset of symptoms of cardiac failure. The first cardial
      manifestation in both patients were palpitations. The first patient, but not the
      second one, had a myeloma confirmed on necropsy.

PMID- 8140758
TI  - [Restrictive infiltrating cardiomyopathy in primary amyloidosis].
AB  - The authors describe a typical echocardiographic finding in restrictive
      infiltrative cardiomyopathy which after two years led to the diagnosis of primary
      amyloidosis in a 51-year-old woman. The predominating manifestations of the
      disease were renal damage with final failure, heart failure, monoclonal
      gammapathy and damage of other organs. Aimed treatment of amyloidosis and
      repeated haemodialysis did not prevent the patient's death from cardiac and renal
      failure. Primary amyloidosis was confirmed by histological examination and
      necropsy.

PMID- 8140759
TI  - [Coronary thrombosis--pathogenic basis of acute coronary syndromes].
AB  - Acute coronary syndromes (unstable angina pectoris, acute myocardial infarction,
      sudden heart death) present an important part of cardiovascular and total
      morbidity and mortality. The common pathogenetic mechanism of them is the break
      of integrity of "stable" atherosclerotic plaque through fissure or rupture with
      following dynamic occlusion of coronary artery. In dynamic occlusion take part
      coronary vasoconstriction and dominant coronary thrombogenesis. Summary review of
      pathogenesis of coronary thrombosis aimed at origin of "unstable" atherosclerosis
      plaque, importance of vessel wall factors, rheologic factors and thrombocytes is
      presented in the paper. Morphologic and structural characteristics of "primary"
      atherosclerotic plaque and of coronary artery lesions in concrete acute coronary
      syndromes are described. From the point of view of clinical practice the authors
      draw attention to the basic importance of thrombin and residual thrombosis in
      acute coronary syndromes. Presented pathogenetic aspects of coronary
      thrombogenesis justify newer therapeutic approaches, which are in the phase of
      intensive research.

PMID- 8140760
TI  - [A review of new cephalosporin antibiotics].
AB  - The authors discuss some properties of recent cephalosporin antibiotics and the
      antibiotics effectiveness in particular of more recent generations of
      cephalosporins. The increasing resistance to penicillins and other antibiotics
      called for use effective cephalosporins of new generations. While cephalosporins
      of the 1st generation (cephalothin, cephazoline, and oral cephaloridine or
      cephaclor) are effective against Gram-positive bacteria, haemophilus bacteria and
      Klebsiellae, the resistance of other bacteria even against these antibiotics is
      increasing. Mephoxine and cephuroxime belong to the 2nd generation as their
      spectrum of efficiency is wider. Cephalosporins of the 3rd generation
      (cefotaxime, ceftriaxone, ceftazidime and others) are effective only against
      strains resistant to cephalosporins of the older generations. Oral preparations
      of cephalosporins of recent generations (Loracarbef, cefpodoxim, ceftibutene) are
      also useful.

PMID- 8140761
TI  - [Interferon alfa in the treatment of monoclonal gammopathies].
AB  - Maintenance treatment with interferon alpha protracts the remission of multiple
      myeloma and this treatment can therefore be recommended. For combined treatment
      of newly diagnosed multiple myeloma so far the optimal dose and time schedule is
      not yet known and therefore combined treatment cannot yet be recommended for
      standard therapy. Similarly, also in primarily resistant or relapsing disease the
      indication of interferon alpha is not yet final and interferon alpha is used in
      this indication only in clinical trials and in common treatment only as the last
      resort. Interferon alpha holds its place in Waldenstrom's macroglobulinaemia.
      Because of the price of interferon alpha it is better to use a cytostatics and
      prednisone as drugs of first choice and administer interferon alpha to patients
      who do not respond to cytostatic treatment. Primary cryoglobulinaemia and primary
      affection of cold haemagglutinin disease are conditions which respond poorly to
      cytostatics and prednisone. Interferon alpha proved in these instances successful
      when used in induction doses of 3 x 10(6) INF-alpha i.u./day.

PMID- 8140762
TI  - [Adverse effects of interferon alfa].
AB  - Interferon treatment means for many patients prolongation of their life. On the
      other hand, this treatment is associated with many undesirable effects listed
      below. Symptoms reminding of influenza (fever, articular and muscle pain,
      fatigue, loss of appetite, gastrointestinal complaints and mild psychic
      irritability) are frequent. As regards laboratory examinations, interferon alpha
      treatment is associated with a drop of the number of leucocytes and to a smaller
      extent also other blood elements and with a rise of liver enzyme levels. Serious
      and life threatening undesirable effects are fortunately rare. In rare instances
      cardiovascular complications were observed (impaired rhythm, drop of blood
      pressure) and sometimes interferon treatment was suspected to be associated with
      myocardial infarction. Interferon alpha can cause deterioration of already
      existing autoimmune disease or cause renal failure. In rare instances psychoses
      induced by interferon alpha were described as well as central and peripheral
      neurological disorders. As the number of patients treated with interferon alpha
      is increasing, all doctors treating these patients should know its undesirable
      effects.

PMID- 8140763
TI  - [New findings in the immunologic classification of malignant lymphomas].

PMID- 8140764
TI  - [Heart transplantation at the Institute of Clinical and Experimental Medicine in
      Prague].
AB  - In the Institute of Clinical and Experimental Medicine in Prague 101 orthotopic
      allotransplantations of the heart were performed in 100 patients (87 men and 13
      women). The reason for transplantation were terminal stages in the first place
      dilated cardiomyopathies and ischaemic heart disease. 58% of the patients survive
      after transplantation, the mortality rate is 42%. The highest mortality is in the
      early postoperative period (within two weeks after operation)--21 cases (50%).
      The longest survival period is nine years and six months. All patients have
      cyclosporin immunosuppressive treatment (in combination with another drug, later
      with another two drugs). In the authors' group in particular incipient acute
      rejections are encountered, "mild" rejections are less frequent and "moderate"
      rejections least frequent. The patients do not reach the stage of advanced acute
      rejection, i.e. "severe" rejection. Acute rejections are treated as a rule with 3
      g Urbason. After this treatment acute rejection improves as a rule completely
      after one or two weeks therapy.

PMID- 8140765
TI  - [Lactobacilli in the treatment of dyspepsia due to dysmicrobia of various
      causes].
AB  - In 30 patients with dyspepsia caused by dysbacteriosis of the gastrointestinal
      tract the authors administered the preparation Lactobacillus acidophilus (Rossel
      Co. Canada)--1. capsule with 2 billion live bacteria, in the morning after
      breakfast. The patients were divided into four groups: maldigestion,
      malabsorption, radiation enterocolitis and administration of antibiotics. The
      patients recorded themselves their subjective symptoms: pain, pressure, bloating,
      flatulence and appetite, and as to objective symptoms, the number and consistency
      of bowel movements, changes of body weight. The most rapid effect was achieved in
      dysbioses after antibiotics--within 3-4 days normalization occurred which
      persisted even after discontinuation of the drug. In maldigestion after one week
      bloating, flatulence, abdominal pain and pressure in the epigastrium was milder,
      and within two weeks the condition improved further. An excellent effect was
      achieved in radiation enterocolitis. In patients with lactose intolerance the
      tolerance of dairy products improved. No side-effects were observed, the
      preparation was very well tolerated; the mean body weight increment was 0.75 kg
      in three weeks. The preparation proved a new useful probiotic which is highly
      effective in dyspepsias caused by dysbiosis of the intestinal microflora.

PMID- 8140766
TI  - [Thrombocytes as an indicator of activity in Crohn's disease treated with total
      parenteral and/or enteral nutrition].
AB  - Inflammatory bowel disease can be associated with increased platelet count. Aim
      of our study was focused on assessing thrombocyte count in evaluation of the
      activity in Crohn's disease (CD). The study included a total of 19 patients [6
      men, 13 women (aged 18-57 years, mean 33, median 28]. All patients were
      malnourished in active stage of the disease on total parenteral and/or enteral
      nutrition (TP/EN). Thrombocytes were estimated at the beginning and after 3 weeks
      of TP/EN in venous blood sample using automatic analyser Coulter Counter JT3
      (normal range: 130-380.10(9)/l). Serum prealbumin, transferrin, haptoglobin,
      alpha 1-orosomucoid and C-reactive protein were measured simultaneously.
      Thrombocytes count below 400.10(9)/l was found only in 1/19 at the beginning and
      in 7/19 patients in the end of the study. After 3 weeks of TP/EN a significant
      platelet count fall was found (mean +/- sd: 472 +/- 98 vs. 354 +/- 110, p <
      0.01). A correlation was found between thrombocytes and serum prealbumin (r = 
      0.3871, p < 0.05), haptoglobin (r = 0.5247, p < 0.001), alpha 1-orosomucoid (r =
      0.4857, p < 0.01) a C-reactive protein (r = 0.4354, p < 0.01). CONCLUSION:
      Thrombocyte count helped in the assessing of disease activity in CD on 3-week
      TP/EN. Improvement of clinical status, increase of nutritional parameters and
      decrease of positive acute phase reactants were associated with a fall of
      platelet count in 15/19 patients.

PMID- 8140767
TI  - [Vasosan S--a cholestyramine in the treatment of hypercholesterolemia of various
      etiopathogenesis].
AB  - Cholestyramine was used for the first time in the treatment of
      hypercholesterolaemia by Tenneton in 1960 and it persist in the treatment to the
      present time. The authors had the opportunity to monitor under clinical
      conditions the hypolipidaemic action of cholestyramine - the preparation Vasosan
      (manufactured by AG Chemie, Germany) in the treatment of hypercholesterolaemia of
      different origin, and also when associated with hypertriacylglycerolaemia. The
      authors revealed that Vasosan S reduced significantly total cholesterol, LDL
      cholesterol and apoprotein B even after brief treatment (12 weeks) even when
      there is also hypertriacylglycerolaemia. The decrease of triacylglycerols is not
      significant, and the increase of HDL-cholesterol is not significant either.
      Vasosan does not affect the activity of AST, ALT, ALP and total bilirubin, it is
      well tolerated and causes few gastrointestinal side-effects which do not call for
      discontinuation of treatment.

PMID- 8140768
TI  - [The effect of compensation in diabetes on left ventricular diastolic filling].
AB  - Examination by Doppler echocardiography in diabetics frequently reveals an
      impaired diastolic function of the left ventricle. However, it is not known this
      disorder is influenced by compensation of diabetes. The author examined therefore
      10 type 1 diabetics, 20 type 2 diabetics without retinopathy and 10 type 2
      diabetics with diabetic retinopathy. He eliminated patients with hypertension,
      valvular defects and manifest IHD. The groups were compared with controls of
      comparable age, sex and habit. Echocardiographic examinations were made before,
      one month after and two months after the onset of intensive insulin therapy.
      Compensation of diabetes was evaluated from the level of glycated proteins. In
      diabetics of type 1 and 2 the authors recorded deterioration of diastolic filling
      of the left ventricle. Short-term compensation led to improvement only in type 2
      diabetics with diabetic retinopathy. The results support effects of close
      compensation of diabetes, as decompensation in patients without late
      complications leads to deterioration of diastolic filling of the left ventricle,
      which at first after compensation is reversible.

PMID- 8140769
TI  - [HLA-B27w (weak HLA-B27)--another subtype of HLA-B27 antigen].
AB  - The authors describe another subtype of antigen HLA-B27, described as HLA-B27P3.
      It was assessed, using 5 anti-HLA-B27 sera. It is identical with the weak antigen
      HLA-B27(HLA-B27w) described by the author in 1976.

PMID- 8140770
TI  - [Long-term survival in multiple myeloma].
AB  - The authors present the results of 23-year protocol studies of survival with
      multiple myeloma, focused on problems of perspective long-term survival. Of 535
      diagnosed patients between 1970 and 1990 the authors checked regularly and
      treated 475. In addition to 60 latent forms where treatment was administered only
      when clinical symptoms developed or after progression of laboratory signs, to all
      patients treatment was administered according to protocols (monotherapy
      cyclophosphamide prednisone in 1970-1975 only to 30 patients, the remainder had
      combined treatment--COPP, VMCP, MOCCA); in the third stage of the disease MOCCA
      treatment is better. The median of survival of patients after VMCP treatment (in
      stage II) MOCCA (in stage III) is more than 90 months, 15% survive for more than
      10 years. The authors emphasize the importance of combined intensive treatment of
      patients for the prognosis of survival. Long-term experience revealed that
      patients achieve an objective response in 85%, while the risk of leukaemic and
      cancerogenic complications is low (1.1%). The therapeutic effect and survival
      period are favourably affected by immunomodulation treatment (Interferon,
      proteolytic enzymes, thymus factor).

PMID- 8140771
TI  - [Foraminal and extraforaminal lumbar disk herniations].
AB  - Between 1985 and 1989, a total of 40 intraforaminal and extraforaminal disc
      herniations were treated, either conservatively or surgically. Lasegue was
      observed in 28%, pain on femoralis extension in 22% and paralysis in 57%. The
      computer discogram was the most sensitive imaging method, with a sensitivity of
      97%. The corresponding values for computerized tomography and NMI were 82% and
      85%, respectively. Nine patients were treated by chemonucleolysis, 19 underwent
      surgery as a primary procedure and three following failure of chemonucleolysis.
      One patient underwent surgery a second time, the first operation having failed.
      The authors report on the indications for various surgical procedures.

PMID- 8140772
TI  - [Long-term changes in proton spin tomography following chemonucleolysis].
AB  - 6.5 years after lumbar chemonucleolysis (CNL) we examined 40 patients by MRI. All
      MRI studies were performed by a 1.0 tesla MRI. We documented the height of the
      discs, the chondrosis, the intradiscal MRI signal, as well as the intraosseous
      signal within the vertebral bodies (end plate reaction). Preoperative MRI studies
      (Tvor) and/or postoperative MRI studies within the first postoperative year (T1)
      of 18 patients were available. We found an overall reduction of the sagittal disc
      height of 26%. This reduction was 19% in the male patients and 45% in the female
      patients (p < 0.02). Comparing the T1-studies with the T6.5-studies, we could
      still reveal a proceeded reduction of 13%. In those patients who underwent three
      MRI studies, there was a reduction of 20% between Tvor and T1. Among one half of
      the patients we found a further decrease in disc height of 15% between T1 and
      T6.5, whereas the other half showed an increasing disc volume of 15%. At time of
      follow up (T6.5) all treated discs showed a reduced MRI signal (STIR) within the
      disc. The signal further decreased comparing the MRI signal (STIR) preoperatively
      with the follow up evaluation in 64.3% of the cases. However, we found an
      increase of the signal in 70% of the cases between T1 and T6.5. 6.5 years after
      CNL we documented an end plate reaction in almost 70% of all patients. There was
      no correlation between end plate reaction and age of the patients, level of CNL,
      amount of injected chymopapain or the clinical outcome.

PMID- 8140773
TI  - [Neuroradiographic diagnosis of degenerative intervertebral disk diseases--the
      Dusseldorf Diagnostic Disk Program. I. Computerized diskography].
AB  - The treatment of disc diseases, in particular the broad spectrum of surgical
      procedures for pathology with radicular and transmitted symptoms, calls for a
      differentiated appraisal of disc pathology. The information content of different
      imaging methods (CT, Disco-CT, NMI) in the various types of degenerative disc
      diseases was compared in a prospective study (92 patients) and verified at
      surgery. In accordance with experimental studies a Discus CT classification
      (Types I-V) was taken as a basis. Categories IV (general degeneration) and V
      (annulus rupture) were divided into three levels of severity (a-c). The
      sensitivity and specificity of Disco-CT for disc herniation, i.e. 97% and 93%,
      respectively, are markedly higher than those of CT or NMI. Similar results were
      obtained in distinguishing different types of disc morphology. The choice of
      imaging procedures for diagnosing causes of sacral/leg pain with radicular
      symptoms is illustrated with reference to the results.

PMID- 8140774
TI  - [Traumatic spondylolysis in the hedgehog. A contribution to the problem of
      isthmus dysplasia].
AB  - Traumatic spondylolysis in a hedgehog is reported. On the basis of that rare
      observation the "dysplastic" thinning of the vertebral isthmus frequently
      associated with spondylolysis in man is claimed to be related to the
      "neuroenveloping" function of the spine shared with that of the neurocranium.
      Dysplasia of the isthmus results from abnormal ganglio-foraminal interrelation in
      the embryo rather than from any primary derangement of the vertebral bone growth
      proper.

PMID- 8140775
TI  - [Idiopathic scoliosis in the sagittal plane].
AB  - Idiopathic scoliosis in sagittal plane is characterised by hypokyphosis and the
      restriction of anteflexion. This we have to take into consideration when we start
      an early treatment. The results are the best in children beyond 8 years of age
      with an angle of Cobb below 20 degrees and in thoracolumbar scoliosis. For the
      beginning idiopathic scoliosis the definition as an error of form is useless. The
      thesis that restriction of anteflexion has the priority in the development of
      idiopathic scoliosis will be supported by the examination of pupils.

PMID- 8140776
TI  - [The surgical treatment of scoliosis of various etiology. Results after 150
      operations using CD-instrumentation with reference to the effects of the
      instrumentation on the sagittal spinal profile].
AB  - At the Orthopaedic University Hospital of Mainz more than 150 patients were
      treated surgically according to Cotrel and Dubousset procedure. By means of this
      operation average corrections of the curves of 54.8% to 64.6% could be achieved
      in the first 150 patients, depending of the localization of the curve. Operative
      procedure, duration of operation and blood loss are adequate to known procedures,
      the stability of the method is better than in other known methods. The change of
      the postoperative sagittal profile demonstrates the influence of the operation in
      cases of hypokyphosis in the thoracic and hypolordosis in the lumbar spine.

PMID- 8140777
TI  - [Aortographic findings in children with myelomeningocele and lumbar kyphosis].
AB  - The findings in abdominal aortography performed preoperatively in 21 children
      with myelomeningocele (MMC), which underwent kyphectomy due to congenital
      kyphosis of the lumbar spine, are reported. In no case did the aorta follow the
      kyphotic radius of curvature. It rather seemed to be strung over the kyphosis
      like a tendon over a bow. An intraoperative lesion of the aorta seems rather
      unlikely, and this is why we believe, that a routinely performed preoperative
      abdominal aortography is not necessary. We found a remarkable number of anomalies
      of the intercostal and segmental arteries, which were only in part associated
      with deformities of the vertebral bodies. The kidneys seemed to be imbedded in
      the kyphotic concavity, partially with the inferior pole, partially in whole. In
      these cases the risk of intraoperative lesion seems higher. We found a number of
      cases with unilateral agenesis of the kidneys in the patients examined by us.
      Therefore we suggest the use of noninvasive methods prior to surgery in order to
      evaluate the presence of malpositions or malformations of the kidneys.

PMID- 8140778
TI  - [Osteosclerosis of the vertebrae in radiological diagnosis and its
      pathomechanism].
AB  - Primarily osteosclerosis is detected in secondary hyperparathyroidism, renal
      osteodystrophia and some renal tubular disorders. As mentioned, the sclerosis of
      vertebral body is often prominent in the regions adjacent to the endplates the
      typical "rugger-jersey-spine". In our study osteosclerosis was detected in about
      10% of the patients with renal osteodystrophia. A still unknown defect in vitamin
      D-metabolism and a increased avidity of the skeleton for calcium may also
      involved. The result of this accumulation of steroid is a net increase of bone
      tissue, with or not mineralization. Conventional radiography is the method of
      choice in detecting typical features.

PMID- 8140779
TI  - [Ventral compression spondylodesis using internal fixator instrumentation--a
      biomechanical study].
AB  - Pseudarthrosis is said to be a main complication in anterior interbody fusion. It
      is usually the result of an insufficient mechanical stability which hinders bony
      incorporation of intervertebral bone grafts. In order to improve stability dorsal
      transpedicular instrumentation should be carried out to achieve interfragmentary
      compression between bone block and adjacent vertebral endplate. Using human
      lumbar spine cadavers and a capacitive measuring mat an experimental study was
      completed to find out in which way an internal fixator has to be used to achieve
      this goal. The collected data showed that simple compression of the fixator by
      reducing the distance between the Schanz-screws did not produce sufficient
      interfragmentary compression. Preloading the fixator in kyphosis and compression
      in a second step improved the results significantly. Using this technique a
      compressive interbody fusion can be attained.

PMID- 8140780
TI  - [Stability of pedicle screws. 1: Maximum pullout force in healthy bony spine
      trunks with reference to drilling technique].
AB  - Pullout direction was axial and oblique to screw axis. Two different techniques
      of preparing the screw bed are matched: 1) 3.2 mm AO drill and 6.0 mm screws for
      D7-S1 and 4.5 mm screws for D11-D6, 2) resection of cancellous bone of the
      pedicle tube and 6.0 mm, 7.0 mm, 8.0 mm screws, which were inserted after
      measuring each level. With the better technique 1 (saving the cancellous bone)
      620N-161N were reached from D1-S1, even if bigger screws could be used with
      technique 2.

PMID- 8140781
TI  - [Stability of pedicle screws. 2: Maximum pullout force with reference to bone
      density].
AB  - Maximum pullout strength of pedicle screws in osteoporotic cadaver spines are
      tested. Bone mineral density was measured before by two noninvasive methods (QCT,
      DRA). Pullout direction was axial to screw axis. 210 N to 920 N were reached from
      D1-S1. There is a high correlation between bone mineral density and pullout
      strength (r = 0, 8-0.9). Augmentation of osteoporotic pedicles with bone cement
      increases screw stability nearly to that one of non-osteoporotic spines.

PMID- 8140784
TI  - [We have thrown the Kardex in the wastebasket].

PMID- 8140782
TI  - [Fluorescence spectroscopy in selective percutaneous nucleotomy using the excimer
      laser--experimental studies].
AB  - Our intention was to test fluorescence spectroscopy as a possibility for
      selective laser ablation. In an experimental setup a XeCl excimer laser (308 nm)
      with pulse energies between 5 and 50 mJ was used for fluorescence excitation in
      20 human and 100 pig vertebral segments. Tissue fluorescence was detected via a
      quartz fiber bundle and analyzed by a polychromator and optical multichannel
      analyzer. Both low and high energy levels led to a broad band fluorescence of
      nucleus pulposus, intervertebral muscle, spinal cord and vertebral end plate and
      a typical fluorescence of anulus fibrosus with peak maxima at 385 and 435 nm.
      Tissue fluorescence was independent of surrounding medium (with air and normal
      saline used) and excitation energy. Borderlines between different tissues could
      be clearly indicated in all cases. Using intensity rations at 350, 385 and 435 nm
      (I1 = I350/I385, I2 = I385/I435) tissue discrimination was possible in all cases.
      This results demonstrate, that discrimination between intervertebral disc and
      surrounding tissue is possible and could be used for selective percutaneous laser
      nucleotomy in the near future.

PMID- 8140783
TI  - [A small majority keeps an eye on health care. Interview by Birgitta Dalenstam].

PMID- 8140785
TI  - [Nurses can give relatives an active role. Interview by Tord Ajanki].

PMID- 8140786
TI  - ["We should be a popular movement". Interview by Tord Ajanki].

PMID- 8140787
TI  - [Estonia-Sweden exchange--a meeting between 2 health care cultures].

PMID- 8140788
TI  - [How do women react to wearing diapers? Silence aggravates problems].

PMID- 8140789
TI  - [Acupuncture helps stroke patients--Katarina's results astonishes physicians.
      Interview by Anders Olsson].

PMID- 8140790
TI  - [It is high time that we are being heard].

PMID- 8140791
TI  - [Let us raise our voices! Inferior care for the weak? Not on your life!].

PMID- 8140792
TI  - [Laboratory technician--a risky job?. Interview by Elisabet Forslind].

PMID- 8140793
TI  - [Guidelines help in ethical dilemmas. Interview by Birgitta Dalenstam].

PMID- 8140794
TI  - [SHSTF cautions on observations in psychiatric report. Without our members unique
      abilities disappear].

PMID- 8140795
TI  - [We already have a personal representative in Ekbacken].

PMID- 8140796
TI  - [Set limits and call the doctor!. Interview by Elisabet Forslind].

PMID- 8140797
TI  - [Not the fault of LAS (Law on Job Protection) that jobs disappear].

PMID- 8140798
TI  - [It is a question of who will have the power. Interview by Maria Ejd].

PMID- 8140800
TI  - [Evaluating seminar in laboratory methods].

PMID- 8140799
TI  - [Where is justice when more than half are dismissed?].

PMID- 8140801
TI  - [Stepping carefully around the problem of euthanasia].

PMID- 8140802
TI  - [Relatives should take part in care].

PMID- 8140804
TI  - [Great interest in quality assurance].

PMID- 8140803
TI  - [Healthy but not free].

PMID- 8140805
TI  - [Accreditation is proof of good quality].

PMID- 8140806
TI  - [Can we put research results into action?].

PMID- 8140807
TI  - [Continuous chase for the invisible nursing care].

PMID- 8140808
TI  - [The final time can be lived fully].

PMID- 8140809
TI  - [Health record follows Johan].

PMID- 8140810
TI  - [Women should have a wage increase!].

PMID- 8140811
TI  - [Team work with SOS in Jamtland. Improved nursing care information with new
      technology and organization. Interview by Kaj Nyman].

PMID- 8140812
TI  - [Diary from the war in Somalia. "One gets so tired of all the gunshot wounds"].

PMID- 8140813
TI  - [The elderly can be passive if we obstruct their development].

PMID- 8140814
TI  - Regulatory effects of the lipid-cytosolic enzyme interaction: AMP deaminase.

PMID- 8140815
TI  - Elongation factors from the Guerin epithelioma and rat liver cells.

PMID- 8140816
TI  - Sulfur amino acid metabolism and its regulation in fungi: studies with
      Aspergillus nidulans.

PMID- 8140817
TI  - The control of L-phenylalanine ammonia-lyase activity by phosphonate and aminooxy
      analogues of phenylalanine.

PMID- 8140818
TI  - Sulfoconjugation of exo- and endogenous phenols: species and tissue specificity.

PMID- 8140819
TI  - Nonidentity of subunits of human kidney arginase A1 and human liver arginase A5.
AB  - The main forms of arginase A1 from human kidney and A5 from human liver were
      purified to homogeneity. Molecular weight of both forms of enzyme approximates
      120,000. In the presence of EDTA these arginases dissociate into single type
      distinct subunits. M(r) of both kinds of subunits is 30,000. Similarly as native
      arginase forms, they differ in electric charge and display complete immunological
      incompatibility.

PMID- 8140820
TI  - Prostaglandin E (dmPGE2) action in vitro on the activity of rat liver Golgi
      apparatus galactosyltransferase.
AB  - In vitro addition of 16,16'-dimethyl prostaglandin E2 to Golgi-rich membrane
      fraction in final concentration of 0.1 microgram/1 mg of protein increased
      generally the activity of galactosyltransferase in comparison with control. The
      percentage of phospholipids in the whole fraction was similar in both
      investigated groups, only the sum of phosphatidylethanolamine+phosphatidic acid
      was significantly lower after addition of dmPGE2 than in the control (0.001 < P <
      0.01).

PMID- 8140821
TI  - Homology of genes for exopolysaccharide synthesis in Rhizobium leguminosarum and
      effect of cloned exo genes on nodule formation.
AB  - A 5.4 kb BamHI fragment of R. leguminosarum bv. trifolii TA1 was found to carry
      genes involved in exopolysaccharide synthesis (exo genes). This fragment was
      strongly hybridized to the total DNA from R. l. bv. viciae and bv. phaseoli
      digested with EcoRI. No homology was found with total DNA of R. meliloti and
      Rhizobium sp. NGR 234. The exo genes from R. l. bv. trifolii TA1 conjugally
      introduced into R. l. bv. viciae 1302 considerably affected the symbiosis: the
      nodules induced on vetch were abortive and did not fix nitrogen. On the other
      hand, Phaseolus beans infected with R. l. bv. phaseoli harbouring R. l. bv.
      trifolii exo genes formed the nitrogen-fixing nodules. It can be concluded that
      additional copies of exo genes introduced into wild type Rhizobium leguminosarum
      strains can disturb the synthesis of acidic exopolysaccharides and affect
      symbiosis of the plants forming indeterminate nodules, but do not affect
      symbiosis of the plants forming the determinate nodules.

PMID- 8140822
TI  - Acoustical investigation of the liposome-saccharide interaction.
AB  - High precision measurements of ultrasonic velocity in aqueous suspension of
      phosphatidylcholine liposomes in the presence of trehalose, sucrose and glucose
      have demonstrated its dependence on the concentration of the two disaccharides.
      This finding is interpreted in terms of replacement by the latter of water
      molecules bound to phosphate head groups on the liposome surface.

PMID- 8140823
TI  - Interactions between the gene products of pma1 encoding plasma membrane H(+)
      ATPase, and pdr1 controlling multiple drug resistance in Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae, the pma1 mutations controlling the vanadate
      resistance of the H(+)-ATPase activity from the plasma membrane, map on
      chromosome VII in the vicinity of pdr1 mutations controlling multiple drug
      resistance. However, the pma1-1 mutants exhibit a genotype and a multidrug
      resistant phenotype quite different from those obtained for pdr1 mutants.
      Quantitative modifications of cycloheximide and N,N'-(p-xylylidene)-bis
      aminoguanidine-2HCl resistance are observed in diploids containing the pma1 and
      pdr1 genes in trans configuration. Each of the pdr1 mutations interacts with pma1
      as shown by a decrease in the ATPase activity in pdr1/pma1 diploids. The in vitro
      resistance of ATPase activity to vanadate is totally or partially suppressed in
      pdr1 mutants in haploid double mutants. These results suggest that the expression
      of PMA1 might be controlled by the PDR1 gene product.

PMID- 8140824
TI  - Phosphorylation of acidic ribosomal proteins by ribosome-associated protein
      kinases of Saccharomyces cerevisiae and Schizosaccharomyces pombe.
AB  - Two proteins of 13 kDa and 38 kDa, the components of 60S ribosomal subunits, were
      identified as phosphorylation substrates for protein kinases tightly associated
      with S. cerevisiae and Schizosaccharomyces pombe ribosomes. An enzyme with
      properties of multifunctional casein kinase II was detected in ribosome
      preparations from both yeast species. In S. cerevisiae another protein kinase
      with high substrate specificity toward those proteins was also identified. By
      using isoelectric focusing, the protein band of 13 kDa from S. cerevisiae and S.
      pombe was resolved respectively into three and four major forms of different
      charge. The same protein forms were phosphorylated in the in vivo 32P-labelling
      experiments.

PMID- 8140825
TI  - Discrimination between chilling-sensitive and chilling-resistant plants based on
      measurements of free fatty acid accumulation and inactivation of oxygen evolution
      in aged chloroplasts.
AB  - The effect of aging of isolated chloroplasts of two chilling-sensitive (CS) and
      three chilling-resistant (CR) plants on the inactivation of oxygen evolution and
      accumulation of free fatty acids (FFA) was studied at 30 degrees C, pH 5.5 or
      7.0, in the absence or presence of either sorbitol or NaCl. Considerable
      accumulation of FFA in aged chloroplasts of CS plants: bean and maize line F7
      RpIII was accompanied by a marked inactivation of oxygen evolution. This relation
      was not, however, found in chloroplasts of CR species: pea, wheat and maize line
      EP1-RpI, in which the accumulation of FFA upon aging was very low whereas the
      decline of the rate of oxygen evolution was pronounced. In contrast to changes
      observed at pH 5.5, the inactivation of oxygen evolution in chloroplasts of CR
      species aged at pH 7.0 was dependent on the composition of the medium, especially
      in wheat chloroplasts. Thus, for the evaluation of chilling sensitivity based on
      the measurements of oxygen evolution activity solely, either aging of
      chloroplasts at pH 5.5 or possibly at pH 7.0 with NaCl included into the
      incubation medium may be recommended. It is concluded that determination of both
      the extent of FFA accumulation and inactivation of oxygen evolution in aged
      chloroplasts might be applied as chilling tolerance indexes.

PMID- 8140826
TI  - The amino acids that constitute sequence gamma 268-282 of fibrinogen are not
      involved in fibrin monomer polymerization.
AB  - Congenitally abnormal fibrinogens with impaired fibrin monomer polymerization
      have been described to contain single amino-acid substitutions localized in
      certain positions of the gamma 275-330 peptide region. To evaluate the role of
      the amino-acid sequence in the vicinity of Arg275 in fibrin monomer
      polymerization, the peptide fragment corresponding to gamma 268-282 was
      synthesized and used to obtain peptide-specific antibodies. These antibodies,
      when purified immunochemically on the immobilized peptide, bound to the intact
      fibrinogen and fibrin monomers with the same binding affinity. However, they did
      not recognize the gamma 268-282 epitopes on the denatured and reduced fibrinogen
      molecules. The lack of influence of antipeptide antibodies on fibrin monomer
      polymerization indicates that the gamma 268-282 peptide is not directly involved
      in the structure of the polymerization site in the D domain of fibrinogen. It is
      suggested that substitution of Arg275 either by His or Cys in abnormal
      fibrinogens results probably in conformational changes which disturb a proper
      orientation of the polymerization site and reduce its expression.

PMID- 8140827
TI  - Changes of nucleotide content in human and rat heart during cardiac surgery and
      ischemia.
AB  - The influence of ischemia on purine nucleotide and their catabolite concentration
      in human myocardium was investigated during surgery of acquired and congenital
      heart defects. This was compared with the influence of ischemia on rat heart.
      Concentrations of adenine and guanine nucleotides and their catabolites were
      measured in the extracts of heart biopsies taken at the onset of ischemia and at
      the time of reperfusion. The content of myocardial ATP in human heart decreased
      from the initial value of 22.3 +/- 1.1 to 14.6 +/- 1.5 nmol/mg protein and total
      adenine nucleotide pool decreased from 34.2 +/- 1.8 to 27.6 +/- 1.5 nmol/mg
      protein during the operation. Significant increases in myocardial concentrations
      of purine catabolites were also observed with the most prominent rise in inosine
      from below 0.5 at the onset of the ischemia to 3.0 +/- 0.5 nmol/mg protein at the
      time of reperfusion. A positive correlation was demonstrated between the
      concentration of purine catabolites in the heart at the end of ischemia with the
      decrease of both ATP and the total nucleotide pool. An interesting metabolic
      specificity of the ischemic human heart appeared to be only a small accumulation
      of inosine monophosphate (IMP). The increase of IMP in the rat heart after
      ischemia was several-fold higher. Thus, cardiac surgery of congenital and
      acquired heart defects was associated with a significant decrease in myocardial
      adenylate pool and a single biopsy collected at the end of ischemia seems to be
      sufficient to evaluate the extent of this metabolic and possibly functional
      impairment of the heart.

PMID- 8140828
TI  - Effect of glucose and deoxyglucose on cytoplasmic concentration of free Ca2+ in
      Ehrlich ascites tumour: studies on single cells.
AB  - Concentration of free cytoplasmic Ca2+ ([Ca2+]i) in Ehrlich ascites tumour cells
      loaded with fura-2 was measured in single cells applying a video imaging system.
      In resting cells [Ca2+]i amounted to 60-340 nM and was increased after addition
      of 10 mM D-glucose or D-2-deoxyglucose by 80-200 nM. This increase occurred
      within 30-60 s following addition of the sugars and lasted for several minutes.
      Pretreatment of the cells with thapsigargin resulted in a much smaller [Ca2+]i
      increase after addition of glucose or deoxyglucose and, vice versa, thapsigargin
      added after the sugars mobilized less Ca2+ than when added before. A possible
      relation of the [Ca2+]i rise evoked by glucose and deoxyglucose to the Crabtree
      effect is discussed.

PMID- 8140829
TI  - Na+,K(+)-ATPase activity of rabbit kidney cortex membranes in ischemia and
      reperfusion.
AB  - The activity of Na+,K(+)-ATPase in the microsomal fraction of rabbit kidney
      cortex was strongly decreased by ischemia and increased slightly, but not
      significantly, after reperfusion. These changes were correlated with a dramatic
      increase in lipid peroxidation in microsomes isolated from both ischemic and
      reperfused kidneys. This correlation may point to irreversible impairment of the
      enzymatic function under the influence of either oxygen free radicals or lipid
      peroxidation.

PMID- 8140830
TI  - A study of the genotoxic potential of flavonoids using short-term bacterial
      assays.
AB  - Genotoxic activities of flavonoids (quercetin, rhamnetin, isorhamnetin, apigenin,
      luteolin) were investigated using two short-term bacterial assays. In the "repair
      test" in Salmonella typhimurium (strains TA1538 uvrB- and TA1978 uvrB+) the
      flavonoids studied did not introduce any damage into the DNA recognized by UvrABC
      nuclease (correndonuclease II). The results of the SOS-Chromotest in Escherichia
      coli K-12 strains PQ37 (tag+, alk+) and PQ243 (tagA, alkA) indicated that
      flavonoids only weakly induced the SOS system. The addition of a liver activation
      system (S9 mix) did not increase the mutagenic effect of the flavonoids tested.
      Two compounds: rhamnetin, isorhamnetin and their putative metabolites formed in
      the presence of the S9 mix did not alkylate DNA at N-3 of adenine.

PMID- 8140831
TI  - Cis-DDP induced alteration of DNA structure studied by scanning tunneling
      microscopy.
AB  - Scanning tunneling microscopy (STM) was used to study the structural changes of
      DNA induced by the antitumor drug cis-diamminedichloroplatinum. The STM image
      showed a dramatic structural perturbation of the DNA by complexed Pt with the
      characteristic bend of the double helix.

PMID- 8140832
TI  - DNA and proteins of the nuclear matrix are the main targets of benzo[a]pyrene's
      action in rat hepatocytes.
AB  - The binding of [14C]benzo[a]pyrene (B[a]P) to DNA and proteins in total nuclei
      and subnuclear fractions of cultured rat hepatocytes was compared. The main
      targets of B[a]P were non-histone high molecular weight proteins of the nuclear
      matrix and DNA sequences attached to this structure. Following 24 h exposure to
      B[a]P the amounts of adducts in the nuclear matrix DNA and proteins were twice as
      high as in total nuclei. After withdrawal of the carcinogen containing medium the
      level of B[a]P-induced adducts gradually decreased but always remained the
      highest in the nuclear matrix proteins. Removal of adducts from the nuclear
      matrix DNA was more efficient than from the other DNA fractions, and 72 h after
      exposure to the carcinogen the level of DNA adducts in this fraction was similar
      to that in total nuclei.

PMID- 8140833
TI  - Changes in lipoprotein lipase activity and plasma liver lipids in thiram
      intoxicated rats.
AB  - Acute thiram (tetramethyl-bis-thiocarbamyl disulphide) poisoning of rat (a single
      dose of 50% LD50) caused decreased lipoprotein lipase (LPL) activity in adipose
      tissue, the greatest inhibition being observed at 72 h after administration of
      the pesticide. Simultaneously, the levels of total plasma cholesterol,
      triacylglycerols and the high density lipoprotein (HDL) cholesterol were
      increased. On repeated pesticide administration (5% LD50) decreased LPL activity
      was observed after 14 and 30 days of poisoning, whereas after 90 days the LPL
      activity was distinctly increased. The levels of total cholesterol (in all
      periods of poisoning) and HDL cholesterol (only after 30 days of poisoning)
      became increased. These changes were accompanied by decreased content of free
      fatty acids and increase of hepatic triacylglycerols. The changes observed in the
      lipoprotein lipase activity of thiram-poisoned rats correspond to the profiles of
      plasma lipoproteins typical of thyroid hypofunction.

PMID- 8140834
TI  - Emergency surgery of complicated colonic diverticulitis.
AB  - Colon diverticular disease is an increasingly frequent disorder especially in
      Western populations characterized by high living standards. In 30-40% of subjects
      over 60 years of age barium enema detects the presence of diverticula in the
      sigma. 10-20% of patients affected by colon diverticular disease develop
      complications such as inflammation or haemorrhage and 20-30% of these patients
      undergo surgery (60% of patients aged less than 40). Emergency surgery is
      performed in 50% of cases and it is currently burdened by high mortality rates.
      We decided to review our cases history to clarify the indication for emergency
      surgery, the appropriateness to resect the diseased bowel tract and to perform
      colic anastomosis at the time of emergency resection.

PMID- 8140835
TI  - Colorectal cancer in patients younger than forty years of age.
AB  - The records of the General Surgery Department of the Cerrahpasa Medical Faculty
      of 10 years duration (1981-1991) were studied retrospectively to determine
      prognostic factors in colorectal cancer patients younger than 40-year old. Fifty
      patients between the ages of 10-39 were identified. The family history was
      positive in 7 of the 50 patients. We found Hematochezia (60%), abdominal pain
      (64%), alterations in bowel movements (60%) among the presenting symptoms. The
      pathologic examination revealed no patients in Dukes Stage A, 14 patients in
      stage B (28%), 36 patients in stage C and D (72%). Distant metastases were
      present in 10%. Mucinous adenocarcinoma was found in 40% of the patients in whom
      an histological differentiation could be made. The 5-year survival rate was 25.7%
      and the 5-year disease free survival rate was 17.1% in the patients who were
      followed up. The mean survival was 30 months. Poor prognostic factors were Dukes
      Stages C and D, sex, age, mucinous/nonmucinous histology, tumour differentiation
      and grade. Patients presenting with one or more of the symptoms above should be
      carefully examined for colorectal cancer regardless of age because of the
      importance of delay and presentation with progressive disease on survival.
      Colorectal cancer is the second leading cause of cancer in the U. S. A. Although
      colorectal cancer is a disease of older group of patients, the incidence of
      colorectal cancer in younger patients is being increasingly reported.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8140836
TI  - Chronic small bowel obstruction due to intestinal malrotation in the older child:
      an often missed diagnosis.
AB  - A case of chronic small bowel obstruction due to intestinal malrotation in a 13.5
      year-old girl is reported. The importance of the patient's history revealing the
      recurrent character of the symptoms, and of different radiological features are
      emphasized, in order to prevent late diagnosis. Diagnosis of psychogenic disorder
      is only retained after exclusion of all organic anomalies. At surgery the bowel
      is placed in the primitive position of the non-rotated gut, after reduction or
      resection of the volvulus, if present.

PMID- 8140837
TI  - Epidermoid cysts of the spleen.
AB  - Primary nonparasitic splenic cysts are very rare. Clinical manifestations vary
      but are often not very typical. Ultrasound and computed tomography are of use for
      establishing diagnosis. A microscopic examination of the surgical specimen is the
      only way to make the diagnosis of an epidermoid cyst. The histological
      characteristic of an epidermoid cyst is the presence of an epidermoid epithelial
      cyst lining of the inner surface. Treatment requires surgery and is necessary to
      prevent serious complications. Spleen saving surgical procedures are advocated.
      We present two cases of young patients with a large epidermoid cyst of the spleen
      who were operated on. On one patient, we had to perform a splenectomy because of
      the size and central localization of the cyst with compression of the splenic
      pedicle. On the other patient we managed to perform a partial splenectomy.

PMID- 8140838
TI  - Perineal repair of procidentia recti with a silastic sling.
AB  - Several operations have been proposed to correct complete rectal prolapse (1, 2,
      3, 4). Perineal approaches in patients with rectal prolapse are recognized as
      less strenuous on the general health of the patient than abdominal methods of
      repair. This has led to the use of perineal procedures for elderly and
      debilitated patients. In our text we describe a perineal repair with a silastic
      sling. In general this technique is designed to treat the prolapse by narrowing
      of the anal outlet and suspension of the rectum.

PMID- 8140839
TI  - Surgical anatomy of the serratus anterior-rib composite flap.
AB  - Dissection of 40 cadavers demonstrates that the serratus muscle has a constant
      anatomy. If it is used as a muscle flap, it is reliable with a consistently long
      pedicle, excellent malleability and multipennate anatomy permitting coverage of
      complex three dimensional wounds of the face and limbs. The anastomosis, around
      the rib, between its vessels and those arising from the intercostal artery are
      useful if it is raised as a rib-composite flap.

PMID- 8140840
TI  - Thrombolysis combined with angioplasty for failed femorodistal arterial grafts.
AB  - This study examines the long-term clinical success and complications of
      thrombolysis-angioplasty (TLA) of failed arterial grafts performed in 17 patients
      (group 1) and matched with 21 patients (groups 2) who had intra-arterial
      thrombolysis (IAT) followed by graft revision. TLA consists of alternating
      thrombolysis with percutaneous transluminal angioplasty (PTA) in the treatment of
      occlusive arterial disease. Failed grafts consisted of 21 vein grafts, 6 ovine
      collagen grafts, 6 polytetrafluorethylene (PTFE) prostheses, 3 human umbilical
      veins and 2 polyurethane vascular grafts. All bypasses were below the knee, of
      which 13 were to the tibial level. Thrombolytic agents used were urokinase in 21
      cases, tissue plasminogen activator in 13 cases and streptokinase in 4 cases.
      Following successful thrombolysis, PTA was performed with a 3 mm to 5 mm balloon
      catheters. Nine tandem lesions were corrected. In all 24 stenoses were treated:
      14 anastomotic stenoses, 4 graft strictures and 5 peripheral stenotic lesions.
      The combined cumulative patency rate of both groups was 36% (SE 10.8%) at 3
      years. The initial technical success rate in group 1 was 70% (12 of 17 grafts).
      The cumulative patency rate, as revealed by life-table analysis, was 35.6% (SE
      10.2%) at one year and 21.3% (SE 9.6%) at 2 years. In all, 10 grafts failed at
      follow-up and in 6 of these cases secondary intervention was unsuccessful. Mid
      graft and isolated lesions responded better than did anastomotic and tandem
      lesions. In group 2 the cumulative patency rate was 60.4% (SE 5.7%) at one year
      and 50.3% (SE 12.9%) at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140841
TI  - Iatrogenic arterial trauma associated with hip fracture surgery.
AB  - During a 5 year period, 1417 patients with various types of hip fractures were
      surgically treated. Three cases of iatrogenic arterial injuries occurred during
      the correction procedures, giving an incidence of 0.21%. In 2 patients the
      profunda femoral and in one the common femoral artery were involved. The
      mechanisms of injury were: a protruding screw, beyond the medial border of the
      femur in the first patient, arterial tear, due to bone speculae in the second and
      external pressure to the artery from an avulsed lesser trochanter in the third.
      The clinical findings were false aneurysms in two and distal ischaemia in the
      third patient. All patients were surgically treated. Early diagnosis of this type
      of injuries is the cornerstone for a good outcome.

PMID- 8140842
TI  - Migration of Kirschner's pin from the right sternoclavicular joint resulting in
      perforation of the pulmonary artery main trunk.
AB  - The spontaneous migration, in a 62-year-old patient, of a broken Kirschner's pin
      from the right sternoclavicular joint to the anterior mediastinum, with
      perforation of the pericardium and puncture of the main trunk of the pulmonary
      artery resulting in cardiac tamponade, is described. A review of the literature
      stresses the high risk of migration when pins or wires are used for internal
      fixation of the shoulder girdle, resulting sometimes in life-threatening
      situations and the need for major thoracic interventions. It seems mandatory to
      remove all foreign material after consolidation, certainly when pins or wires are
      broken or when there is evidence of local bone resorption, as the broken parts
      may migrate. The legal implications, when adequate and regular follow-up has been
      neglected, are described.

PMID- 8140843
TI  - Paraprosthetic fistula after aortobifemoral prosthetic reconstruction: treatment
      by autogenous saphenous venous replacement. A case report.
AB  - Paraprosthetic fistula is a rare but dramatic complication of aortofemoral
      prosthetic reconstruction. Conventional treatment consisting of removal of the
      prosthesis and extra-anatomical revascularization results in a high morbidity and
      mortality rate. The authors present a patient with a paraprosthetic fistula, who
      was successfully treated by excision of the graft and "in situ" replacement by
      autogenous saphenous vein.

PMID- 8140844
TI  - An uncommon breast tumour: the malignant eccrine spiradenoma. A case report.
AB  - Eccrine spiradenoma is a benign tumour originating from cutaneous sweat glands.
      It rarely develops into a malignant tumour. A long-standing cutaneous nodule
      begins to enlarge rapidly. The growth is often associated with an ulceration and
      a change in colour. The definitive diagnosis is made after a biopsy with
      examination of the entire specimen in search for foci of malignant development.
      The appropriate therapy consists in a wide local excision, with resection of the
      clinically suspicious lymph nodes. Irradiation of the resection site can be
      useful to prevent local recurrences. The role of chemotherapy is not yet clearly
      defined.

PMID- 8140845
TI  - Giant ovarian cyst.
AB  - Case report of a patient with a giant ovarian cyst. On the basis of literature
      data, surgery and histology problems, as well as oncological therapy are
      discussed.

PMID- 8140846
TI  - Validation of a new serologic test for the detection of Helicobacter pylori.
AB  - In order to determine normal ranges for positive and negative titres using a new
      commercially available second generation serologic ELISA test for the detection
      of Helicobacter pylori IgG antibodies (Malakit by Biolab, Limal, Belgium) we
      investigated 560 asymptomatic pregnant women aged 20 to 44. 128 patients (22.9%)
      had a positive titre for Helicobacter pylori. Although we were able to observe an
      increase of the number of seropositive subjects with advancing age, a significant
      increase in titre with age, both for positive and negative titres, could not be
      demonstrated. Although there was a much higher prevalence of Helicobacter pylori
      seropositivity in patients with a non-caucasian ethnic background, we did not
      observe a significant difference in cut-off limit between the different ethnic
      populations. In all seropositive patients a control serology and 13C-urea breath
      test were performed 4 to 6 months later. In 124 patients (96.9%) both control
      examinations were positive. The positivity of the 13C-urea breath test suggests
      an existent Helicobacter pylori infection in these (symptom-free) women. 13C-urea
      breath tests were also performed in 100 randomly selected seronegative women and
      were all negative, as well. Since 13C-urea breath tests were positive in
      seropositive subjects and negative in seronegative women, we validated the
      manufacturer's previously established cut-off values, based on only 37 adult
      patients, in a much larger population.

PMID- 8140847
TI  - [Crohn's disease in prolonged remission: should one augment protein-calorie
      intake as compared to healthy subjects?].
AB  - The aim of our two year prospective study was to evaluate whether adult Crohn's
      disease patients in prolonged remission (CDAI < 150), in order to maintain their
      body weight as close as possible to the ideal one, need a protein-calorie intake
      higher than the predicted one and that of healthy controls. Twenty-four out of 49
      Crohn's disease patients in clinical remission completed the two year prospective
      study, during which they were free to eat "ad libitum", in quantity and in
      quality. Twenty-three of the 24 patients (96%) maintained their body weight > 95%
      of the ideal one. As compared to predicted intakes, mean calories were -12.23% (=
      272 +/- 91 Kcal/day) lower (P < 0.01), and proteins +40.6% (20.16 +/- 13.6 g/day;
      = 0.32 g/kg b.w./day) higher (p < 0.001). Protein-calorie intake and glycolipid
      ratio were comparable to those of healthy controls (p = n.s.). In the group of
      patients who had a relapse during the follow-up, 9 out of 25 were found to be
      underweight at the onset of the survey. Their protein-calorie intake was
      equivalent to that of subjects who completed the study. We conclude that adult
      Crohn's disease patients in prolonged remission maintain their ideal body weight
      by a protein-calorie intake comparable to that of healthy population and do not
      need a tailored regimen.

PMID- 8140848
TI  - Short-chain carboxylic acid in the feces in patients with pancreatic
      insufficiency.
AB  - Short-chain carboxylic acids in the feces of 12 patients with chronic
      pancreatitis having steatorrhea and 18 healthy subjects were determined by high
      performance liquid chromatography. The fecal amount of the patients with chronic
      pancreatitis was increased to about twice that of the control, and the fat in the
      feces increased to eight times. The excretion of short-chain carboxylic acids
      increased to about three times. The short-chain carboxylic acid concentration
      regarded as derived from protein or amino acid, such as iso-butyrate,
      isovalerate, and n-valerate, was significantly increased in patients with chronic
      pancreatitis. From the above results, our data suggest that there is maldigestion
      of protein besides that of carbohydrate. And we confirmed that these data are an
      in-vivo illustration of the phenomena which have been studied in-vitro
      experiments, when fecal bacteria were incubated with peptide or amino acids as a
      substrate.

PMID- 8140849
TI  - [Neuroendocrine regulation of eating behavior].
AB  - We review current neuroendocrine concepts about feeding behavior. Digestive or
      metabolic inputs are conveyed to the hypothalamus by endocrine and neuroendocrine
      pathways (insulin, cholecystokinin). The hypothalamus regulates feeding behavior
      both quantitatively and qualitatively through several neuroendocrine mediators
      (neuropeptide Y, galanin, GHRH...). The hypothalamus also integrates, by its
      communicative network, inputs from the cortex, the sub-cortex, the peripheral
      metabolism and it modifies consequently the feeding behavior. These
      neuroendocrine models are developed from many experimental observations both in
      normal and obese animals.

PMID- 8140850
TI  - [Crohn's disease of the esophagus. Apropos of a case].
AB  - A case of oesophageal Crohn's disease associated with large bowel lesions and
      with ocular, articular and cutaneous manifestations is reported. The patient, a
      45 year old woman, was successfully treated with corticosteroids. The authors
      review the literature about oesophageal involvement in Crohn's disease and extra
      intestinal manifestations.

PMID- 8140851
TI  - [Hypersensitivity interstitial pneumopathy and ulcero-hemorrhagic rectocolitis:
      role of methotrexate].
AB  - The authors report the case of a 46-year-old man with refractory ulcerative
      colitis treated with methotrexate who was admitted in the hospital for asthenia,
      fever, cough and dyspnea. Owing to the development of adult respiratory distress
      syndrome despite broad spectrum antibiotherapy, the patient was transferred to
      the intensive care unit. A diagnosis of pneumonitis due to methotrexate was made.
      Patient's condition improved after discontinuation of the drug, mechanical
      ventilation, and corticosteroids. The increasing use of methotrexate in several
      gastroenterological diseases warrants further consideration of the potential
      devastating side effects of this drug, particularly on the lungs. A review of the
      literature on this topic is provided in the "discussion" section.

PMID- 8140852
TI  - Appearance of a gallstone in a patient with systemic lupus erythematosus during
      ursodeoxycholic acid treatment.

PMID- 8140853
TI  - An unusual foreign body swallowed by a newborn causing respiratory distress.
AB  - Swallowed and inhaled foreign bodies in children under 5 years of age are common
      and considered serious causes of morbidity and mortality. However such occurrence
      is uncommon in infants and newborns. The current report deals with a strange
      object lodged in the oesophagus of a 20-day-old male newborn.

PMID- 8140854
TI  - Latent membrane protein 1: a key oncogene in EBV-related carcinogenesis?

PMID- 8140855
TI  - Levels of tumor necrosis factor alpha/cachectin (TNF alpha) in sera from patients
      with sickle cell disease.
AB  - Serum levels of tumor necrosis factor alpha/cachectin (TNF alpha) were studied in
      a group of adult patients with sickle cell disease (SCD), which include 31
      patients with homozygous SS hemoglobinopathy and 10 patients bearing double
      heterozygous SC hemoglobinopathy and in their matched normal controls. All
      patients tested did not show any form of crisis for at least 4 weeks prior to the
      extraction of the sample. The amount of TNF alpha in serum was quantitated by
      means of an immunoenzymatic assay with a lower limit of detection of 25 pg/ml.
      The percentage of sera with detectable levels of TNF alpha was significantly
      increased in SCD patients as compared with the normal controls. Mean TNF alpha
      values in individuals with detectable levels of the cytokine were also
      significantly higher in the whole group of SCD patients and in patients bearing
      either SS or SC hemoglobinopathies than in the control group. An inverse
      correlation was observed between the percentages of Hb F and the levels of TNF
      alpha found in the sera from the patients.

PMID- 8140856
TI  - Molecular characterization of Hb H disease by polymerase chain reaction.
AB  - We utilized the PCR method to amplify the alpha-thalassemia-1 breakpoint area of
      the Southeast Asia type and several regions of the alpha-globin gene cluster to
      diagnose rightward deletion (-alpha 3.7), leftward deletion (-alpha 4.2) or
      nondeletion forms of the Hb H disease. For the nondeletion form, a natural
      restriction site of MseI was used to detect the Hb Constant Spring (Hb CS) or
      other termination codon mutations. Another naturally occurring restriction site
      of MspI was used to detect the Hb Quong-Sze. For the deletion form of the Hb H
      disease, the differences among nonhomologous I, II and III of the rightward or
      leftward deletion were used to distinguish the mutations. For further
      characterization of the subtype of -alpha 3.7 deletion, the same primers for
      detecting termination codon mutations were used to amplify part of the alpha
      globin gene, then the PCR product was digested by the restriction enzyme ApaI. In
      the 57 cases which were studied, 19 were deletion forms while 38 were nondeletion
      forms. In the deletion form cases, 13 were rightward deletion (-alpha 3.7) and
      the other 6 were leftward deletion (-alpha 4.2). However, all of the nondeletion
      form cases were alpha-thalassemia-1 with Hb CS. After the subtyping of -alpha 3.7
      deletion, 11 out of 13 were type I deletions and the other 2 were type II
      deletions.

PMID- 8140857
TI  - Flow-cytometric analysis of reticulocytes in normal cord blood.
AB  - We performed precise reticulocyte counts and a reticulocyte maturation study
      according to ribosomal RNA (rRNA) content, in normal cord blood. For this purpose
      we analyzed 35 cord blood specimens corresponding to a mean gestational age of
      39.2 weeks (range 38-41). In all specimens complete blood counts were performed
      with the H*1 (Technicon, Bayer) analyzer. Reticulocyte maturation study and
      counts were conducted by the R-1000 (Sysmex) reticulocyte analyzer. We obtained
      the following measurements (mean +/- 1 SD): reticulocyte percentage 3.11 +/-
      0.75% and reticulocyte absolute count 137.3 +/- 33.3 x 10(9)/l. There was no
      correlation between the reticulocyte counts and the duration of gestation or the
      type of labor (normal, forceps assisted or cesarean section). Reticulocyte
      subpopulations with different rRNA content and maturation were expressed as
      reticulocytes with high (HFR), median (MFR) and low (LFR) fluorescence of the
      fluorochrome auramine bound to rRNA. Normal cord values were: HFR% = 13.6 +/-
      2.4, MFR% = 22.5 +/- 2.4 and LFR% = 63.9 +/- 4.3. Reference maturation
      subpopulations were assessed for comparison in 180 samples of healthy adults (90
      males and 90 females) and were found HFR% = 1.0 +/- 0.8, MFR% = 9.7 +/- 3.3 and
      LFR% = 89.2 +/- 3.4. The HFR% and MFR% were significantly higher while LFR% was
      significantly lower (p < 0.001) in cord compared to adult blood, denoting a shift
      to more immature reticulocyte forms. The above values are provided as normal
      reference data of the reticulocyte maturation profile in full-term cord blood.

PMID- 8140858
TI  - Fluorescent in situ hybridization for the detection of t(8:14) in Burkitt's
      lymphoma.
AB  - Burkitt's lymphoma cells exhibit the reciprocal balanced chromosomal
      translocation t(8:14) in 75% of patients. Cytogenetic analysis is time-consuming,
      requires in vitro culture with mitogens and enables to analyse a relatively small
      number of cells. We evaluated the role of multicolor fluorescent in situ
      hybridization (FISH) in the rapid detection of t(8:14) in Burkitt's lymphoma
      cells. FISH detected the JH/myc translocation in 100% of the cells of five cell
      lines carrying the classical t(8:14) and in fresh cells obtained from a newly
      diagnosed Burkitt's lymphoma patient. In contrast, the translocation was not
      detected in the Bajb cell line that does not carry t(8:14). We conclude that FISH
      is a rapid and reliable diagnostic tool for the detection of the JH/myc
      translocation in Burkitt's lymphoma patients.

PMID- 8140859
TI  - Philadelphia chromosome as the sole abnormality and p210 bcr-abl chimeric protein
      expression in an Epstein-Barr virus-transformed B cell line from a patient with
      chronic myeloid leukemia.
AB  - A 'B' cell line, originating from a patient with chronic myeloid leukemia and
      containing the Philadelphia chromosome, was established after Epstein-Barr virus
      transformation. The Philadelphia chromosome was the sole chromosomal abnormality
      in this line, designated as PhB1 cell line. In DNA hybridization studies we
      detected rearrangements in the bcr gene and in the immunoglobulin heavy chain
      joining region. The phenotypes of the cells were typical of mature B cells
      expressing antigens CD19, CD20, CD22, CD23, CD39, HLADR, IgM, and kappa. The
      expression of the 210 bcr-abl chimeric protein was detected by means of an
      immunoprecipitate assay.

PMID- 8140860
TI  - Probable acenocoumarol-amoxycillin interaction.
AB  - We present the case of a woman undergoing treatment with acenocoumarol for deep
      vein thrombosis, who maintained an international normalized ratio (INR) of
      between 2.5 and 4 for 2 months. Seven days after the introduction of amoxycillin
      (500 mg/8 h) for a probable respiratory infection, the patient developed
      spontaneous bruising, with an INR of 7.1. Treatment with amoxycillin was
      discontinued, and 3 weeks later the INR had returned to previous values. In this
      case, the increase in the INR value with associated bruising after the addition
      of amoxycillin suggests a drug interaction between acenocoumarol and amoxycillin,
      other possible causes having been eliminated.

PMID- 8140861
TI  - Splenic lymphoma with villous lymphocytes. Report of first 2 cases from the
      Middle East.
AB  - Two cases of splenic lymphoma with villous lymphocytes (SLVL) were diagnosed on
      the basis of marked splenomegaly, circulating villous lymphocytes, serum IgM
      monoclonal paraprotein and bone marrow infiltration. Immunological studies
      confirmed the B cell phenotype (CD19+, CD20+, CD22+ and CD5- and CD25-).
      Ultrastructural studies revealed characteristic uneven villi with polar
      predisposition. Interferon-alpha therapy in 1 patient did not result in any
      clinical or hematological improvement. This is the first report of SLVL from the
      Middle East.

PMID- 8140862
TI  - Angiotensin-converting enzyme inhibition and anaemia in renal patients.
AB  - A 35-year-old renal transplant patient with stable renal function developed an
      unexplained anaemia. Appropriate investigations proved non-diagnostic. Only when
      enalapril therapy was stopped did the anaemia reverse and haemoglobin levels
      returned to pre-treatment levels. An association between angiotensin-converting
      enzyme inhibitors and anaemia in patients with renal failure is becoming more
      evident. A literature review of this problem and its possible pathogenesis in
      patients with renal failure is given.

PMID- 8140863
TI  - Importance of central nervous system involvement by neoplastic cells in a patient
      with Waldenstrom's macroglobulinemia developing neurologic abnormalities.
AB  - The clinicopathology of central nervous system (CNS) involvement with tumor
      formation in the brain of a patient with Waldenstrom's macroglobulinemia (WM) who
      developed neurologic abnormalities in the absence of blood hyperviscosity is
      reported. Extravascular infiltration by monoclonal lymphoplasmacytoid cells with
      considerable perivascular disruption of the brain and reactive gliosis was a
      conspicuous histopathologic picture. The tumor as well as the patient's
      neurologic symptoms were successfully controlled by local radiation to the brain.
      This case report illustrates the importance of CNS involvement by neoplastic
      cells in the differential diagnosis of a patient with WM developing neurologic
      abnormalities.

PMID- 8140864
TI  - Could chelation therapy with deferoxamine enhance the percentage of responders to
      interferon therapy in chronic hepatitis C?

PMID- 8140865
TI  - Cataract after prolonged busulphan therapy.

PMID- 8140866
TI  - Morphologic evidence of in vivo differentiation in acute myeloblastic leukemia.

PMID- 8140867
TI  - Drug interactions with intravenous and local anaesthetics.
AB  - Relatively few clinically significant drug interactions with anaesthetics have
      been documented in the literature. The following should be stressed since these
      interactions are not readily predictable or are potentially fatal. Pethidine
      should never be administered to patients who have received monamine oxidase
      inhibiting drugs within the last fortnight, since a fatal hyperpyrexia and/or
      hypertension may result. Thiopentone induction seems to make the heart more
      susceptible to arrhythmias caused by adrenergic drugs, and may cause severe
      arterial hypotension in patients treated with diazoxide. Midazolam orally should
      possibly be avoided as premedication in patients treated with erythromycin since
      anaesthetic concentrations of midazolam may result. Patients for whom bupivacaine
      analgesia is planned could preferentially be premedicated with other drugs than
      diazepam, which causes the serum level of bupivacaine to increase. Bradycardia
      and hypotension not attributable to sympathetic blockade have been reported
      following bupivacaine extradurally in verapamil-treated patients. Sulfonamides
      and the ester group of local anaesthetics, such as prilocaine in combination, may
      result in severe methaemoglobinaemia in infants. Epinephrine added to local
      anaesthetics may cause local vasodilation if administered to patients
      concurrently being treated with cyclic antidepressants, and the combination
      imposes the risk of severe hypertension and arrhythmias.

PMID- 8140868
TI  - Wound infiltration with local anaesthetics.

PMID- 8140869
TI  - Effects of propofol on the human heart electrical system: a transesophageal
      pacing electrophysiologic study.
AB  - Previous studies have shown that infusion of propofol has sometimes been
      associated with bradyarrhythmias. To evaluate the effects of propofol on the
      electrical system of the heart, we carried out an electrophysiologic study with
      transesophageal pacing on ten healthy subjects scheduled for minor elective
      maxillo-facial surgery. By means of atrial pacing conducted by a progressive
      increase in stimulation cycles, we determined, in awake patients and during
      propofol anesthesia (2.5 mg kg-1 for induction, followed by 100 micrograms kg-1
      min-1 for maintenance), the correct sinus recovery time and the eventual
      appearance of Wenckebach atrio-ventricular block. We did not notice sinoatrial
      node depression or pathologic increase in the atrio-ventricular conduction.

PMID- 8140870
TI  - Amelioration of respiratory and circulatory changes in established endotoxic
      shock by ketoprofen.
AB  - In an intensive-care setting we studied the effects of ketoprofen, a dual
      inhibitor of cyclooxygenase and lipoxygenase, on circulatory and respiratory
      changes during established endotoxic shock in sheep. Two groups (n = 7 in each)
      were exposed to E. coli endotoxin, which caused a sharp increase in pulmonary
      artery pressure (200%; PAP), intrapulmonary shunt fraction (300%; QS/QT%), and
      oxygen extraction ratio (50%; VO2/DO2%). There was also a significant decrease in
      mean arterial pressure (25%; MAP), respiratory compliance (60%; CT), arterial
      oxygen tension (65%; PaO2), and oxygen delivery index (15%; DO2) in both groups.
      After 30 min of endotoxin infusion, group K received ketoprofen, 2.5 mg/kg b.w.
      i.v., while group E served as shock controls. After 4 h there had been a
      significant improvement in MAP, PaO2, DO2, QS/QT%, and CT in the ketoprofen
      treated group compared with the controls (P < 0.01). In addition, the oxygen
      extraction ratio normalised in group K, but remained 70-100% increased in group E
      (P < 0.01). The wet-to-dry weight ratios of the lungs and the liver were
      significantly lower in the ketoprofen-treated group compared with the controls (P
      < 0.05). It was concluded that ketoprofen significantly ameliorated the
      respiratory and circulatory effects of established endotoxic shock in sheep.

PMID- 8140871
TI  - Effect of nitrous oxide and volatile anaesthetics on platelet function in man.
AB  - Twelve otherwise healthy male volunteers scheduled for arthroscopy of the knee
      were studied. The influence in vivo of nitrous oxide (N2O) per se and the
      addition of a halogenated volatile anaesthetic (halothane or isoflurane) on ADP
      induced platelet aggregation and release of beta-thromboglobulin into plasma was
      evaluated. All measurements were made before surgery. We found that N2O increased
      platelet aggregation. Adding a halogenated anaesthetic reversed the relative
      hyperaggregation induced by N2O. The concentrations in plasma of the platelet
      release product beta thromboglobulin were not influenced by the anaesthetics.

PMID- 8140872
TI  - Flumazenil facilitates intraoperative arousal during scoliosis surgery: a
      randomized, double-blind, placebo-controlled study.
AB  - Intraoperative arousal was evaluated in 24 patients (median age 16.5 years),
      undergoing spondylodesis with Cotrel-Dubousset or Harrington-Luque
      instrumentation. Flumazenil and placebo groups of 12 patients each were similar
      with respect to age, body weight, dosage of anaesthetic drugs and surgery times.
      Premedication consisted of diazepam 0.2-0.3 mg kg-1 orally. Anaesthesia was
      induced with thiopentone 5-7 mg kg-1, and maintained with 66% nitrous oxide in
      oxygen, and repeated doses of fentanyl, midazolam and atracurium. After placement
      and fixation of the metal rods, N2O was switched off, and either flumazenil or
      placebo was given in refracted doses until the patient responded to command.
      Intraoperative motor response times (medians with ranges), defined as the time
      from the injection of the first dose until the patient responded to command, were
      2.5 min (1.0-5.2 min) after flumazenil, and 8.0 min (1.7-28.5 min) after placebo
      (P = 0.02). Five patients in the placebo group did not wake up within 10 min and
      received naloxone. The quality of awakening was similar in both groups. Two
      patients (one in each group) woke up violently and needed physical restraint.
      Postoperatively, motor responses were assessed after 12.0 min (5-42 min) in the
      flumazenil group, and after 15.2 min (4-40 min) in the placebo group (NS).
      Recovery from anaesthesia took 27.5 min (7-415 min) in the flumazenil group, and
      25.0 min (8-160 min) in the placebo group (NS). One patient given flumazenil and
      one patient given placebo remembered moving their feet, but neither of them could
      recall anything unpleasant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140873
TI  - Effects of ephedrine and phenylephrine on maternal and fetal atrial natriuretic
      peptide levels during elective cesarean section.
AB  - The effects of ephedrine and phenylephrine on fetal and maternal plasma atrial
      natriuretic peptide (ANP) concentrations were studied during 30 elective cesarean
      sections. After induction of spinal anesthesia, reductions from baseline maternal
      blood pressure were corrected with one of these pressor agents administered in a
      double-blinded, randomized manner. Immediately following delivery, umbilical
      artery (UA) ANP concentrations were significantly higher than umbilical vein (UV)
      concentrations (pg/ml) for both groups (ephedrine, 120.8 +/- 64.0 vs. 86.8 +/-
      40.8, phenylephrine, 125.0 +/- 54.2 vs. 72.4 +/- 31.7), but there were no
      differences between groups for UA and UV ANP levels. Postpartum maternal ANP
      concentrations were significantly higher than baseline values in both groups, but
      again there were no differences between groups. Correlations between total doses
      of ephedrine or phenylephrine and UA or UV ANP levels did not reach significance.
      Postpartum maternal (MV2), UA, and UV blood gas variables (pH, PCO2, and PO2)
      were also not different between groups. These data suggest that effects of
      pressor doses of ephedrine (beta and alpha agonist) and phenylephrine (alpha
      agonist) on maternal and fetal ANP levels are not different. Therefore, 1)
      assuming these pressor drugs stimulate ANP release, this stimulation is not
      solely mediated by beta receptors and 2) to the extent that fetal ANP influences
      feto-placental circulatory homeostasis, the effects of ephedrine and
      phenylephrine on this regulatory mechanism do not appear to be different.

PMID- 8140874
TI  - Postoperative nausea and vomiting. A comparison between intravenous and
      inhalation anaesthesia in breast surgery.
AB  - Nausea and vomiting during the first 24 postoperative hours after breast surgery
      were studied. Ninety patients scheduled for elective breast surgery were randomly
      assigned to one of three anaesthetic methods: total intravenous anaesthesia with
      propofol, or propofol or thiopental for induction followed by isoflurane
      anaesthesia. All three groups received fentanyl for peroperative analgesia. A
      total of 46 (51%) patients experienced emetic sequelae: 19 (21%) complained about
      nausea and another 27 (30%) vomited once or more during the postoperative course.
      More than 50% of the patients with nausea and 70% with vomiting first suffered
      from these symptoms in the surgical wards after leaving the postoperative unit.
      Nausea and vomiting were seen in 18 (60%), 13 (43%) and 15 (50%) for the groups
      propofol-propofol, propofol-isoflurane and thiopental-isoflurane, respectively.
      In conclusion, every second patient experienced nausea or vomiting after breast
      surgery, the majority of these emetic symptoms occurring after leaving the
      postoperative unit. Propofol for induction or as a main anaesthetic did not make
      any major difference with regard to postoperative nausea or vomiting.

PMID- 8140875
TI  - Effects of epidural morphine and epidural bupivacaine on gastroduodenal motility
      during the fasted state and after food intake.
AB  - The effects of a thoracic epidural analgesia with morphine or bupivacaine on
      gastroduodenal motility during the fasted state and after food intake were
      evaluated in healthy volunteers. Nine volunteers were studied on two occasions,
      separated by at least 2 weeks, and were randomly allocated to receive either
      epidural morphine or epidural bupivacaine at the T6-T7 level on each occasion.
      Gastroduodenal motility was measured by manometry. Acetaminophen absorption was
      used as an indirect measure of the rate of gastric emptying and orocecal transit
      time was determined by use of the hydrogen breath test after ingestion of
      raffinose. During the control measurements, before the epidural analgesia, there
      were no differences in gastroduodenal pressure activity between the morphine and
      bupivacaine groups. Compared to epidural bupivacaine, epidural morphine
      significantly changed the pressure activity with a higher number of contractions
      in the duodenum, both during the fasted state and after food intake. Retrograde
      pressure activity was seen in the duodenum after epidural morphine but not after
      epidural bupivacaine. There were no significant differences in the pressure
      activity in the stomach after epidural morphine compared to epidural bupivacaine.
      Gastric emptying was delayed and orocecal transit time prolonged after epidural
      morphine. This study in volunteers showed that epidural morphine, compared to
      epidural bupivacaine, significantly changed the gastroduodenal motility, both
      during the fasted state and after food intake.

PMID- 8140876
TI  - Importance of modes of acupuncture in the treatment of chronic nociceptive low
      back pain.
AB  - A controlled study of different modes of acupuncture stimulation was conducted on
      patients fulfilling clinical criteria for chronic low back pain of nociceptive
      origin. Forty patients were randomly entered into the study. Thirty had three
      trial treatments with manual stimulation of needles (MS), electrical low
      frequency stimulation at 2 Hz (LF), and high-frequency stimulation at 80 Hz (HF),
      and then continued treatment with the mode they felt most benefitted them. Ten
      patients were put on the waiting list for treatment but served as the untreated
      control group. The results were evaluated after 6 weeks and at 6 months for:
      activity related to pain; mobility; verbal descriptors of pain and the patient's
      subjective assessment of his condition. After 6 weeks, patients receiving
      treatment showed significant improvement (P < 0.05 to P < 0.001) on three of the
      four measures compared to the untreated controls. After 6 months a similar
      measure of significant improvement was seen in patients continuing with low
      frequency (LF) acupuncture, but not in those groups continuing with manual
      stimulation (MS) or high-frequency (HF) acupuncture. The results suggest that 2
      Hz electrical stimulation is the mode of choice when using acupuncture in the
      treatment of chronic nociceptive low back pain.

PMID- 8140877
TI  - Wound infiltration with local anaesthetics for postoperative pain relief.

PMID- 8140878
TI  - Attenuation of arterial baroreflex control of renal sympathetic nerve activity
      during lidocaine infusion in alpha-chloralose-anesthetized dogs.
AB  - The purpose of this study was to identify the relationship between sensitivity of
      arterial baroreflex and plasma concentrations of lidocaine. Using twelve mongrel
      dogs anesthetized with alpha-chloralose, the left kidney was exposed
      retroperitoneally, and renal sympathetic nerve activity was recorded
      continuously. Lidocaine was infused in four different doses: 2 mg.kg BW-1 bolus +
      100 micrograms.BW-1 x min; 3 mg.kg BW-1 bolus + 200 micrograms.kg BW-1 x min; 6
      mg.kg BW-1 bolus + 400 micrograms.kg BW-1 x min; and 12 mg.kg BW-1 + 800
      micrograms.kg BW-1 x min. Baroreflex depressor and pressor tests using sodium
      nitroprusside (5-10 micrograms.kg-1) and phenylephrine (2-4 micrograms.kg-1) were
      performed before and at 10 min after beginning lidocaine infusion. Plasma
      lidocaine concentrations determined by high performance liquid chromatography
      revealed that the steady-state levels were maintained during the baroreflex
      tests. Baroreflex sensitivity was preserved at plasma concentrations of lidocaine
      below 5 micrograms.ml-1. However, cardiac and sympathetic baroreflex sensitivity
      were significantly attenuated (P < 0.01) when plasma lidocaine concentrations
      were well above human convulsion levels (10 micrograms.ml-1). The results
      indicate that hemodynamic derangement observed in the lidocaine-induced central
      nervous system toxicity is, at least in part, due to the attenuated arterial
      baroreflex.

PMID- 8140879
TI  - Adenosine protects ultrastructure of isolated rat lungs against fat emulsion
      injury.
AB  - In isolated rat lungs subjected to fat emulsion damage, a model simulating adult
      respiratory distress syndrome, we have previously reported that adenosine (ADO)
      reduces pulmonary vascular resistance (PVR) and the fluid filtration rate (FFR).
      In the present study the aim was to examine morphologically this effect of ADO.
      Two groups of isolated rat lungs were subjected to the injury. Marked and
      significant differences were found between the groups; in lungs not given ADO,
      FFR and airway pressure were higher and, as evaluated by electron microscopy, the
      endothelial lining was thin and partly disrupted. The epithelial cells of the
      alveolar walls were also partly disrupted and the alveolar septa were split
      enclosing interstitial edema. In lungs receiving ADO from the onset of exposure
      to fat emulsion, FFR was lower and ultrastructure did not differ from non-injured
      non-treated controls perfused for the same length of time.

PMID- 8140880
TI  - Aerosolized surfactant reverses respiratory failure in lung-lavaged rats.
AB  - The effects of surfactant replacement by aerosol inhalation and by bolus
      instillation were compared in rats with respiratory failure induced by repeated
      lung lavage. The rats were anesthetized with pentobarbital sodium and
      mechanically ventilated with 100% oxygen. The PaO2 of control rats not given
      surfactant (n = 9) remained below 13 kPa. A bolus instillation of a modified
      natural surfactant (75 mg.kg-1 b.w. in 1.5 ml.kg-1 b.w. saline) into the airways
      rapidly reversed the respiratory failure; the mean PaO2 value (n = 9) 15-180 min
      after instillation remained over 50 kPa (P < 0.05 vs. controls). Inhalation of
      the aerosolized surfactant for 60 min through an ultrasonic nebulizer delivering
      < or = 75 mg.kg-1 b.w. of the surfactant into the lungs gradually reversed the
      respiratory failure. The mean PaO2 value (n = 9) 15 min after initiation of
      inhalation was 19.6 kPa (NS vs. controls), but after 60 min it rose to above 43
      kPa (P < 0.05 vs. controls; NS vs. bolus instillation). Treatment with surfactant
      either by continuous aerosol or by bolus led to significant increases of over 24%
      in the dynamic lung-thorax compliance. We conclude that aerosolized surfactant
      reverses respiratory failure induced by lung lavage, although the response is
      slower than after bolus instillation.

PMID- 8140881
TI  - Halothane concentrations for malignant hyperthermia testing.

PMID- 8140882
TI  - Use of the laryngeal mask airway to facilitate fibreoptic bronchoscopy in awake
      patients.

PMID- 8140883
TI  - Stroke subtypes and risk factors associated with silent infarctions in patients
      with first-ever ischemic stroke or transient ischemic attack.
AB  - The relationship between the presence of silent cerebral infarcts (SCI) and
      etiology of an acute cerebral ischemia remains controversial. In a population of
      306 patients with a first-ever stroke (225) or transient ischemic attack (TIA)
      (81), we studied the prevalence and associated risk factors of SCI as well as the
      presumed etiology of the qualifying event. Silent infarction was defined as a
      focal hypodensity on brain CT, not related to the recent ischemic event. The
      overall prevalence was 33% (102/306) with a higher rate in stroke patients
      (83/225, 37%) than in TIA patients (19/81, 23%; p = 0.028). Age (p < 0.01),
      smoking (p < 0.01), hypertension (p = 0.013), and leukoaraiosis (p = 0.05) were
      significantly associated with SCI, but only in some degree in TIA patients.
      Presence of SCI was statistically associated with a small-artery disease (p <
      0.01) considered as the cause of the qualifying event. Emboligenic cardiopathy
      was significantly more frequent in patients without SCI (p < 0.05) in the TIA
      subgroup. Thus, in patients with silent cerebral infarcts, small-vessel disease
      may be in most cases the cause of the recent symptomatic cerebral ischemia.

PMID- 8140884
TI  - Secondary prevention of stroke: does dipyridamole add to aspirin?
AB  - BACKGROUND AND PURPOSE: The purpose of this paper is to evaluate, in the light of
      all available evidence, the place of aspirin alone and of aspirin combined with
      dipyridamole in the secondary prevention of cerebrovascular accidents. METHODS:
      We performed a meta-analysis of all identified double blind, controlled, studies
      in secondary prevention of cerebrovascular accidents for the following
      categories: studies comparing aspirin with placebo; studies comparing aspirin
      plus dipyridamole with placebo; studies comparing aspirin plus dipyridamole with
      aspirin alone. An indirect comparison was carried out to compare the results
      obtained with aspirin alone and those obtained with aspirin combined with
      dipyridamole. RESULTS: The meta-analysis of trials involving aspirin alone
      against placebo showed a risk reduction on strokes (17% reduction, p = 0.02),
      "important vascular events", i.e. a combination of vascular deaths, non-fatal
      strokes and non-fatal myocardial infarction (18% reduction, p = 0.003). Fatal
      vascular events (vascular deaths and fatal strokes) did not seem to be reduced at
      all. The overall mortality was reduced by 10%, but this reduction failed to reach
      statistical significance (p = 0.23). The meta-analysis of trials involving
      aspirin combined with dipyridamole showed more important risk reductions on every
      outcome whether fatal or not. Strokes were reduced by 42% (p < 0.001), fatal
      strokes by 43% (p = 0.02) and vascular deaths by 24% (p = 0.07, not significant).
      The overall mortality was reduced by 30% (p = 0.004). Direct comparisons of
      aspirin with aspirin plus dipyridamole did not indicate differences between the
      two treatment regimens. However the sample sizes involved in these comparisons
      were far too small to be informative. Indirect comparisons yielded statistically
      significant results in favour of the combination in terms of "important vascular
      events" (p = 0.007), all strokes (p = 0.007) and fatal strokes (p = 0.03). The
      results were also in favour of the combination but not statistically significant
      in terms of all deaths (p = 0.10) and vascular deaths (p = 0.08). CONCLUSIONS:
      Aspirin used alone reduces secondary occurrence of vascular events in
      cerebrovascular patients. There is no evidence, however, of a reduction of fatal
      events (vascular deaths and fatal strokes). In contrast, aspirin in combination
      with dipyridamole reduces non-fatal as well as fatal events. These results as
      well as the indirect comparisons of the risk reductions suggest that the
      combination of aspirin with dipyridamole may be superior to aspirin alone; this
      hypothesis is presently tested in a large randomized trial.

PMID- 8140885
TI  - Filum terminale ependymoma revealed by acute cauda equina compression syndrome
      following intratumoral and spinal subarachnoid hemorrhage in a patient on oral
      anticoagulants.
AB  - A 65 year-old woman with a filum terminale ependymoma is reported, presenting
      with acute cauda equina compression syndrome due to intratumoural and subsequent
      spinal subarachnoid hemorrhage (SAH) following therapy with oral anticoagulants.
      Few cases of spinal ependymoma have been reported with an acute cauda equina
      compression syndrome as the initial and only symptom, and the unique feature of
      our patient's anticoagulant status has only been described once in this setting.
      Although intratumoural hemorrhage is very well known since the myxopapillary
      variant is unique to the cauda equina and consists of loose connective tissue and
      numerous small blood vessels that are prone to bleeding, spinal SAH is seldom
      seen and the different hypotheses about the pathophysiological mechanisms that
      might promote bleeding still remain unresolved and will be discussed in this
      paper, as well as the special clinical features of spinal SAH and some diagnostic
      and therapeutic implications. A review of the literature (Medline search 1983
      1993) revealed only 13 cases, including ours, of spinal SAH due to cauda equina
      ependymoma, and the results of this review together with our findings are
      described in this paper.

PMID- 8140886
TI  - Neuropeptide Y plasma levels and serum dopamine-beta-hydroxylase activity in MS
      patients with and without abnormal cardiovascular reflexes.
AB  - An impairment in the autonomic function has been demonstrated in patients with
      multiple sclerosis (MS) using electrophysiological, pupillary and biochemical
      tests. Particularly evident were alterations in the cardiovascular reflexes,
      cutaneous sympathetic response and lymphomonocyte adrenergic binding.
      Electrophysiological and biochemical findings in MS patients have only
      occasionally been compared. Among the peripheral markers of the autonomic system,
      Neuropeptide Y (NPY) and dopamine-beta-hydroxylase (DBH) have been singled out as
      reliable indices of sympathetic function. The former is a peptide with a strong
      vasoconstrictive action, which is released from adrenergic endings together with
      noradrenaline following sympathetic activation. The latter is the enzyme which
      catalyses the conversion of dopamine to norepinephrine. It is located both in
      sympathetic endings and the chromaffin granules of adrenal medulla. To verify a
      failure in autonomic function in the course of MS, a battery of cardiovascular
      tests (assessing sympathetic and parasympathetic functions) was performed on 25
      MS patients. The results were compared with a group of 20 age- and sex-matched
      control individuals. The plasma levels of NPY and the serum DBH activity were
      also determined in both groups. 52% of patients showed an impairment in
      sympathetic function in one or more tests (sustained handgrip, postural
      hypotension, cold face test). 48% of the patients had abnormal values in deep
      breathing test, indicating a failure of the parasympathetic function. 44% of
      patients showed also a paroxysmal tachycardia after cold face test, indicating an
      abnormal function of the vagal-cardiac and sympathetic-vascular smooth muscle
      pathways of the trigeminal nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140887
TI  - Isolated oculomotor nerve palsy.

PMID- 8140888
TI  - Multiple sclerosis: methodological aspects of cognitive testing.
AB  - In a cross-sectional study of 94 patients (42 males, 52 females) with definite
      multiple sclerosis (MS) in the age range 25-55 years, the correlation of
      neuropsychological tests with the ability to read TV-subtitles and with the use
      of sedatives is examined. A logistic regression analysis reveals a significant
      correlation between results of an attention and perceptual motor speed test i.e.
      Symbol Digit Modalities test and the ability to read TV-subtitles, but no
      correlation was found with another attention and perceptual motor speed test, or
      verbal or visual memory. No correlation between the use of sedatives and results
      on neuropsychological tests was found. Anxiety was not correlated with the
      ability to read TV-subtitles. It is concluded that visual deficits but not the
      use of sedatives may be a confounding factor in neuropsychological testing in MS.

PMID- 8140889
TI  - [Pseudotumoral medullary syndrome manifesting a probably beginning multiple
      sclerosis. Clinical, radiological and neuropathological correlations].
AB  - A 19-y old sportsman was admitted because he complained of ascending paresthesia
      since two weeks, muscular strength diminution in both arms, then respiratory
      difficulties without fever. Clinical examination confirmed an asymmetric
      bilateral pyramidal syndrome affecting the four limbs, a hyposensitive level up
      to C5, without meningeal symptoms. MRI detected a widening of the cervical (C2
      C5) spinal cord, with gadolinium enhancement. CSF demonstrated lymphocytic
      pleocytosis and total protein of 530 mg/l with an oligoclonal IgG pattern. With a
      diagnosis of multiple sclerosis, a corticoid therapy was started but without
      clinical improvement. Six weeks later, a new MRI revealed an increased
      enlargement of the cervical spinal cord suggesting a tumoral process. No tumor
      could be detected at neurosurgery. Biopsy specimen (from C3-C4) demonstrated an
      inflammatory demyelinating disease with astrocytic hypertrophy. Electron
      microscopy confirmed the active demyelinating disorder with persistently denuded
      axons. Several macrophages were observed, but no lymphocytic invasion. Astrocytes
      were prominent in some areas with "en plaque" gliosis. MRI failed to discover any
      other demyelinating lesions. Further clinical evaluation was inconspicuous, the
      patient regaining full activities after 6 months. MRI after 9 months demonstrated
      no spinal cord lesion. This observation contributes to suggest the influence of
      the blood-brain barrier breakdown on the occurrence of clinical and radiological
      signs of new lesions in suspected multiple sclerosis.

PMID- 8140890
TI  - The nature and time course of neuronal vacuolation induced by the N-methyl-D
      aspartate antagonist MK-801.
AB  - N-Methyl-D-aspartate (NMDA) antagonists cause neuronal vacuolation in the
      posterior cingulate and retrosplenial cortex of the rat. Because the nature of
      neuronal pathologic changes due to NMDA antagonists may affect the potential
      clinical use of this class of drugs, we undertook experiments to define the
      nature and time course of the vacuolation caused by high-dose (5 mg/kg) MK-801
      (dizocilpine, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine).
      Ultrastructural examination revealed the vacuoles to be not a form of hydropic
      cellular degeneration, but rather a dilatation of several intracellular
      compartments, chiefly endoplasmic reticulum and mitochondria. Study of the time
      course of the alterations revealed no light or ultrastructural features of
      neuronal necrosis in over 1 thousand neurons examined in layers 3 and 4 of the
      cingulate and retrosplenial cortex, 153 of which were vacuolated. The vacuoles
      resolved over time by decreasing in magnitude. Oxalate-pyroantimonate methodology
      revealed no redistribution of cell calcium in either vacuolated or non-vacuolated
      neurons. At 6 h, when vacuoles were consistently prominent in glutaraldehyde
      fixed plastic-embedded tissue, a separate series of experiments was undertaken to
      vary methods of tissue preparation, and determine conditions under which
      vacuolation occurs. Frozen sections revealed no vacuoles. Subsequent paraffin
      embedding of the previously frozen tissue revealed no vacuoles, but vacuoles were
      seen in paraffin after perfusion fixation. Immersion fixation with brain
      refrigeration for 12 h prior to fixation revealed no vacuoles. Alcohol fixation
      also led to no visible vacuoles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140891
TI  - Reducing body myopathy and desmin storage in skeletal muscle: morphological and
      biochemical findings.
AB  - We describe clinical, morphological and biochemical findings of a patient with
      reducing body myopathy (RBM). This 15-year-old patient was affected by severe
      limb-girdle progressive myopathy with asymmetric distribution. Muscle biopsy
      showed many fibers with cytoplasmic polymorphic masses, which stained dark purple
      with modified Gomori's trichrome, associated with proliferation of cytoplasmic
      bodies. Cytoplasmic polymorphic masses showed marked reducing activity with
      menadione-nitro blue tetrazolium reaction. Ultrastructurally, there was great
      amount of highly electron-dense tubular-filamentous structures of 16-17 nm in
      diameter. Immunohistochemistry showed that many fibers were positive for desmin.
      Sodium dodecyl sulfate-electrophoresis disclosed an increase in two bands of
      approximately 53 and 70 kDa, and Western blot demonstrated that the 53-kDa band
      was desmin. It was not possible to characterize the 70-kDa protein further.

PMID- 8140892
TI  - Herpes simplex virus type 1 strain KOS-63 does not cause acute or recurrent
      ocular disease and does not reactivate ganglionic latency in vivo.
AB  - The virological, clinical, and histopathological manifestations of acute and
      experimentally reactivated infections of eyes and trigeminal ganglia have been
      studied following intranasal infection of rabbits with herpes simplex virus type
      1 (strain KOS-63). All animals shed virus in nasal secretions, but only three
      shed virus in tear film during the first 12 days of infection. No animal
      developed clinical or histological evidence of corneal or retinal ocular disease
      at any time after infection. KOS-63 established trigeminal ganglionic latency;
      viral RNA, restricted to neuronal nuclei, was detected by in situ hybridization,
      and virus was recovered from co-cultivation cultures of nervous tissue, but not
      from cell-free homogenates. Reactivation of latent trigeminal ganglionic
      infection was attempted by intravenous administration of cyclophosphamide,
      followed by dexamethasone 24 h later. Injection of the drugs failed to reactivate
      KOS-63 latency; no animal shed virus in nasal or ocular secretions, and no animal
      developed gross or microscopic corneal lesions. In addition, viral antigens were
      not detected by immunofluorescence microscopy in ganglia from rabbits subjected
      to the drug protocol, and virus was only recovered from ganglia by in vitro co
      cultivation reactivation techniques. The failure of KOS-63 to reactivate was not
      due to an inherent failure of populate and infect the ganglion, because the virus
      did not reactivate from ganglia that contained many latently infected cells.
      These studies demonstrate that, although KOS-63 is neuroinvasive and capable of
      establishing latency, it is virtually nonvirulent for the eye, and cannot be
      reactivated by a systemic immunosuppressive trigger known to reactivate other HSV
      1 strains.

PMID- 8140893
TI  - Involvement of clathrin light chains in the pathology of Alzheimer's disease.
AB  - Clathrin, which constitutes coated vesicles, plays important roles in neuronal
      functions. In the brains of the patients with Alzheimer's disease, distribution
      of clathrin was immunohistochemically investigated using four monoclonal
      antibodies against clathrin light chains, LCB.1, LCB.2, X-16 and CON.1, to study
      the involvement of clathrin in the pathology of Alzheimer's disease. LCB.1,
      LCB.2, X-16, and CON.1 bind to the aminoterminus of the clathrin light chain
      b(LCb), to the neuron-specific insert of LCb, to the light chain a(LCa), and to
      LCa and LCb, respectively. In Alzheimer brains, granular staining of LCB.2 around
      neurons in the hippocampus was weaker or patchily defected in comparison with
      control brains. Some neurofibrillary tangles and neurons were intensely stained
      in Alzheimer brains by LCB.2, whereas neurons were weakly stained in control
      brains. Crowns of some senile plaques in the brains of early onset Alzheimer's
      disease were positively stained by LCB.2. LCB.1 supported the observations of
      LCB.2. Reactive astrocytes in Alzheimer brains were intensely stained by X-16. On
      the other hand, Western blot analysis using LCB.2 and X-16 demonstrated no
      apparent differences in protein amounts and molecular weights of LCa and LCb
      between control and Alzheimer brains. These observations demonstrated abnormal
      distribution of clathrin in Alzheimer brains, implying impairment of axonal
      transport in this disease.

PMID- 8140894
TI  - Early detection of axonal injury after human head trauma using
      immunocytochemistry for beta-amyloid precursor protein.
AB  - Severe non-missile head injury commonly results in a form of brain damage known
      as diffuse axonal injury (DAI). The histological diagnosis of DAI is made by
      silver staining for the presence of axonal retraction balls. This feature takes
      about 24 h to develop and does not allow for the early histological diagnosis of
      DAI. We have used immunocytochemistry for the beta-amyloid precursor protein
      (beta APP) as a marker for axonal injury in formalin-fixed, paraffin-embedded
      sections of human brain. Axonal beta APP immunoreactivity was present in all
      cases which had survived for 3 h or more. This was true even where the degree of
      head injury did not appear to be severe, supporting the theory that DAI is a
      severe form of a more common phenomenon of axonal injury which occurs after
      cerebral trauma. beta APP immunoreactivity was also found in some non-head
      injured cases and so cannot be considered to be a specific marker for trauma. The
      results show that beta APP immunocytochemistry may be useful in the detection of
      traumatic axonal injury in its early stages, before the formation of axonal
      retraction balls, provided care is taken to exclude other causes of such
      immunoreactivity.

PMID- 8140895
TI  - Jun, Fos, MyoD1, and myogenin proteins are increased in skeletal muscle fiber
      nuclei after denervation.
AB  - After denervation, mRNA levels of the jun and fos protooncogenes and of the
      muscular differentiation factors myoD1 and myogenin are increased. Here,
      immunohistochemistry was used (a) to show that this increase in mRNA is followed
      by an increase in the transcription factor proteins, and (b) to determine which
      cell populations in skeletal muscle express these factors after denervation. Rat
      diaphragms were denervated and analyzed after periods of 90 min-8 days. An
      increase in Fos and Jun as well as MyoD1 and Myogenin immunoreactivity was found
      after 2-2.5 days of denervation. Fos, MyoD1, and Myogenin immunoreactivity was
      mostly confined to muscle cell nuclei, whereas Jun antibodies stained muscle cell
      and some interstitial cell nuclei. A selective expression of any of the four
      transcription factors in muscle cell nuclei closely associated with motor
      endplates could not be detected in either denervated or innervated muscle at any
      time point examined, indicating that synaptic and extrasynaptic muscle cell
      nuclei are activated simultaneously after denervation. These results suggest that
      a genetic program which includes protooncogenes and myogenic differentiation
      factors is activated in skeletal muscle after denervation.

PMID- 8140896
TI  - Schwann cell mitochondrial alterations in peripheral nerves of rabbits treated
      with 2',3'-dideoxycytidine.
AB  - 2',3'-Dideoxycytidine (ddC) is a nucleoside analogue and reverse-transcriptase
      inhibitor that is approved for treatment of AIDS patients. A rabbit model of ddC
      neurotoxicity was developed to help understand the dose-limiting clinical
      neurotoxicity of ddC. Rabbits with a myelinopathy resulting from treatment with
      ddC exhibited mitochondrial alterations in Schwann cells of sciatic and tibial
      nerves and dorsal root ganglia. These changes were initially evident after 16
      weeks of oral treatment with 35 mg/kg per day of ddC and were positively
      correlated with myelin pathology in individual animals. Cup-shaped mitochondria
      were frequently observed; when these mitochondria occurred in multiple concentric
      arrays or at various angles to one another, different profiles were formed
      depending on the plane of section. An increased number of mitochondrial cristae
      assumed a tubular configuration. It is suggested that the complex aggregations of
      mitochondria seen in this experiment are an adaptive response to altered
      mitochondrial function caused by treatment with ddC.

PMID- 8140897
TI  - Extracellular ATP induces stellation and increases glial fibrillary acidic
      protein content and DNA synthesis in primary astrocyte cultures.
AB  - A number of factors appear to be involved in the proliferative and hypertrophic
      processes which characterize reactive astrocytosis. We have investigated the
      possibility that ATP, an agent that is released by injured cells following tissue
      destruction, may be one such factor. For this purpose, we utilized primary
      cultures of astrocytes derived from cerebral cortices of neonatal rats to study
      the effect of extracellular ATP on properties associated with astrogliosis. Light
      microscopic studies disclosed marked stellation of astrocytes after 30-60 min of
      exposure to 100 microM-1 mM ATP. In addition, the content of the astrocyte
      specific intermediate filament, glial fibrillary acidic protein (GFAP), was
      increased 35-40% following 60-min exposure to ATP; this effect persisted for 1-3
      days of exposure to 100 microM ATP. [3H]Thymidine incorporation increased
      progressively from 1-3 days; a 3.6-fold increase in DNA synthesis was observed
      following 3 days of exposure to 1 mM ATP, suggesting stimulation of cellular
      proliferation. These findings show that high micromolar to low millimolar
      concentrations of extracellular ATP reproduce several features associated with
      reactive gliosis and suggest that extracellular ATP may be involved in the
      activation of astrocytes following CNS injury.

PMID- 8140898
TI  - Altered expression of antithrombotic molecules in human glioma vessels.
AB  - A total of 14 surgical specimens, including 7 glioblastomas, 3 anaplastic
      astrocytomas, 2 brains adjacent to glioblastoma and 2 grossly normal brains, were
      investigated immunohistochemically for the expression of antithrombin III (AT
      III), heparan sulfate proteoglycan (HSPG) and thrombomodulin (TM) in the
      endothelium of microvessels. The immunoreaction to AT-III was of moderate
      intensity in grossly normal brains, brains adjacent to glioblastoma, and
      anaplastic astrocytomas, but was only weak in glioblastomas, especially in the
      capillaries. The immunoreaction to HSPG was constantly intense in the
      microvessels in all the specimens. Although the immunoreaction to TM was negative
      or only faint in the microvessels in grossly normal brains, it was moderately to
      strongly intense in anaplastic astrocytomas and brains adjacent to glioblastoma.
      The intensity of immunoreaction to TM was variable, from faint to strong in the
      capillaries, and moderate to strong in larger microvessels in glioblastomas. The
      present study suggested that the alterations in the expression of those
      antithrombotic molecules could explain, at least in part, the tendencies for
      intratumoral hemorrhage as well as intravascular thrombosis in the different
      areas of malignant gliomas.

PMID- 8140900
TI  - Exercise and training during graded leg ischaemia in healthy man with special
      reference to effects on skeletal muscle.
AB  - The influence of graded leg muscle ischaemia on the adaptation to training and on
      the acute response to exercise was studied in healthy subjects. Graded ischaemia
      during supine exercise was induced by application of 50 mmHg external pressure on
      the legs. This procedure reduced leg blood flow by 16%, venous oxygen saturation
      by 12 percentage units, and markedly increased lactate release (p < 0.05 for
      all). One-legged training was performed during four weeks, 4 sessions per week.
      Each session started with one leg training for 45 min with reduced blood flow
      (ischaemic training). The contralateral leg, serving as a control, was then
      trained with an identical power-output profile for 45 min but without flow
      restriction (non-ischaemic training). Ischaemic training enhanced the adaptation
      to training. Peak oxygen uptake and time to fatigue increased more (p < 0.05)
      with ischaemic than with non-ischaemic training. Citrate synthase activity,
      capillaries per fibre, and glycogen content were greater (p < 0.05) in the
      trained than in the detrained state. In the ischaemically trained leg, the type
      IIb fibre proportion was lower (p < 0.05) and the I fibre proportion tended to be
      higher (p = 0.06) in the trained than in the detrained state. Maximum voluntary
      dynamic strength was decreased by 8% (p < 0.01) in the ischaemically trained leg,
      but was unaffected in the non-ischaemically trained leg. During acute ischaemic
      exercise, as compared to non-ischaemic exercise, there was a higher degree of
      glycogen depletion, a greater depletion of type II, but not of type I fibres, a
      greater electromyographic activity, higher catecholamine concentrations, lower
      intramuscular ATP and creatine phosphate content, and an increased nitric oxide
      formation as estimated by increased plasma nitrate content. In conclusion, the
      mechanisms underlying the potentiation of the adaptation to training by ischaemia
      are assumed to depend on the operation of stimuli which were amplified during
      acute ischaemic exercise.

PMID- 8140899
TI  - Small arterial granular degeneration in familial Binswanger's syndrome.
AB  - A 55-year-old mildly hypertensive woman died after having developed a subcortical
      dementia during the past 9 years, with focal neurological signs. She presented at
      the age of 46 years with short episodes of dizziness and diplopia, suggesting
      that transient ischemic attacks involved the posterior fossa structures. Over the
      next 8 years, she developed difficulty in walking, urinary incontinence and
      seizures. On examination in 1989, she was severely demented. There was
      tetraparesis, bilateral arm and leg spasticity with hyperreflexia and bilateral
      Babinski signs. She showed epilepsia partialis continua involving the eyes, left
      hemiface and limbs. CT showed hypodensity of the white matter and lacunes in the
      basal ganglia and centrum semiovale, moderate hydrocephalus with cerebellar and
      cortical atrophy. Clinical and radiological features were similar to those of
      Binswanger's disease. Similar cases had occurred in the family affecting the
      patient's grandfather, father and two brothers, suggesting an autosomal dominant
      hereditary disease. Postmortem examination disclosed a Binswanger type of
      leukoencephalopathy caused by a peculiar microangiopathy characterized by a
      slightly basophilic small arterial granular degeneration of the medial sheath
      associated with the presence of ballooned smooth muscle cells with clear
      cytoplasm. Electron microscopic study revealed degenerative changes in the
      parietal vessels with notable increase of basal-membrane-type material and
      electron-dense granular deposits. These lesions could correspond to a specific
      familial pathology of the small arteries of the brain. They are identical to
      those reported in some patients with autosomal dominant inheritance. For other
      patients with similar clinical features and the same familial pattern, reported
      as "hereditary multi-infarct dementia'' and "chronic familial vascular
      encephalopathy'', there are no sufficient objective pathological facts to
      consider that they have the same disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140901
TI  - Morning bright light therapy for sleep and behavior disorders in elderly patients
      with dementia.
AB  - Fourteen inpatients with dementia showing sleep and behavior disorders (average
      age = 75 years), and 10 control elderly people (average age = 75 years) were
      carefully observed for 2 months. Four weeks of morning light therapy markedly
      improved sleep and behavior disorders in the dementia group. The measurement of
      sleep time and the serum melatonin values suggests that sleep and behavior
      disorders in the dementia group are related to decreases in the amplitude of the
      sleep-wake rhythm and decreases in the levels of melatonin secretions. Morning
      light therapy significantly increased total and nocturnal sleep time and
      significantly decreased daytime sleep time. These results indicate that morning
      bright light is a powerful synchronizer that can normalize disturbed sleep and
      substantially reduce the frequency of behavior disorders in elderly people with
      dementia.

PMID- 8140902
TI  - The detection of mental disorders in the community using a 20-item interview
      version of the General Health Questionnaire.
AB  - A 20-item interview version of the General Health Questionnaire (GHQ) was used to
      presumptively identify cases with mental disorders in a sample of 810 community
      residents. Subjects also were examined by psychiatrists using the Present State
      Examination (PSE). The screening instrument performed well in detecting PSE
      CATEGO syndromes related to anxiety and depression, but less well in detecting
      psychotic syndromes and cognitive impairment. The overall sensitivity of the
      instrument for any PSE-CATEGO syndrome was 48%. The study elucidates the specific
      nature of the psychopathology that this version of the GHQ is likely to detect in
      the community.

PMID- 8140903
TI  - A new self-rating scale for depression and anxiety states based on the
      Comprehensive Psychopathological Rating Scale.
AB  - Self-assessment scales have long been used in psychiatric research even if their
      validity has often been questioned, one reason being poor the concordance of
      expert ratings. In clinical practice the use of rating scales is restricted,
      since they are considered to be time-consuming and perhaps even to disrupt the
      clinician's rapport with the patient. In the present study, a self-assessment
      scale, the CPRS Self-rating Scale for Affective Syndromes (CPRS-S-A), was
      constructed by re-phrasing in a self-rating format 19 items from the original
      Comprehensive Psychopathological Rating Scale (CPRS) and covering depression,
      anxiety and obsessional symptoms. In a group of 30 patients with depression
      syndromes and anxiety syndromes, the CPRS-S-A and the original CPRS were both
      used on 2 occasions. The patient's Global Assessment of Functioning scores ranged
      from 30 to 76 (mean 58), which suggests a moderate severity of illness, as does
      the fact that the majority were outpatients. There was a high degree of
      concordance between the instruments for most items and for the scores on the
      subscales for both diagnostic groups (i.e., the Montgomery-Asberg Depression
      Rating Scale and the Brief Anxiety Scale, which are both subscales drawn from the
      CPRS). The time taken to complete the CPRS-S-A varied from 5 to 30 min (mean 19
      min for depressive and 16 min for anxiety patients on the first occasion, 13 min
      for both groups on the second), and the self-rating procedure was readily
      accepted by both groups of patients. The CPRS-S-A would thus seem to be a
      promising instrument for quantitative rating of symptoms in ambulatory patients,
      both in clinical practice and in research.

PMID- 8140904
TI  - Mortality and suicide rates of involuntarily committed patients.
AB  - The mortality and suicide rates for involuntarily committed patients in Denmark
      are presented. Two cohorts of psychiatric patients committed to a mental hospital
      from January 1, 1971 to December 31, 1975 (8322 people) and January 1, 1981 to
      December 31, 1985 (5253 people) have been followed. The standard mortality rate
      (SMR) in relation to the total Danish population were 4.9 (4.5-5.4) and 5.2 (4.7
      5.8), respectively, for the two cohorts, during the first year after
      involuntarily commitment to a mental hospital. During the same period, the SMR
      for suicide among the committed patients were 44.9 (37.1-53.9) and 30.9 (24.2
      38.9), respectively. The crude suicide rates among the committed patients during
      the first year after the commitment were 14.3 and 14.0, respectively, per 1000
      years, unchanged between the cohorts. Short length of stay in hospital (< 14
      days), a nonpsychotic main diagnosis, male sex, and age 35 years or more were
      equally related to high risk of suicide in the 1971 cohort as evaluated to
      proportional hazard methods (Cox regression), and short length of stay and
      commitment on the danger indication provided the most information in relation to
      high suicidal risk in the 1981 cohort. Methodological problems and the reasons
      for the results are discussed.

PMID- 8140905
TI  - Criminality and platelet monoamine oxidase activity in former juvenile
      delinquents as adults.
AB  - Platelet monoamine oxidase (MAO) activity was estimated in 70 former delinquent
      boys and 40 controls now aged 38-46 years. Platelet MAO activity was compared
      with their early criminal behaviour (before the age of 15) and their late
      registered criminality from the age of 15). Mean platelet MAO activity in
      subjects with both early and late criminality was significantly lower than that
      in former delinquents without late criminality. There was no significant
      difference in mean platelet MAO activity between controls and delinquents with
      early but no late criminality. When delinquents with early criminality were
      divided into a low and a high MAO group, the relative risk to be registered for
      late criminality was about 3.1 times higher for the subjects in the low MAO
      group. Thus, individuals with low platelet MAO activity run an increased risk of
      continued criminal behaviour.

PMID- 8140906
TI  - Prophylactic effect of mianserin on recurrent depression.
AB  - The prophylactic effect of mianserin on recurrent depression was studied in a
      double-blind comparison with an inactive placebo by analyzing the recurrence rate
      and the number of depressive episodes in 9 mianserin-treated (daily dose 20-60
      mg) and 13 placebo-treated patients. The selected patients were those who had a
      higher incidence of recurrence (more than 2 depressive episodes during the 2
      years preceding the study). During the 18-month study period, 4 of 9 mianserin
      treated patients and all 13 placebo-treated patients had recurrences. The ratio
      between patients with recurrence and total patients (recurrence ratio) was lower
      in the mianserin-treated group throughout the study, and the intergroup
      difference from the 3rd to the 18th month was significant. In the mianserin
      treated group, the frequency of episode recurrence during the study period was
      significantly lower and the total duration of episodes was significantly shorter
      than those in the placebo-treated group. The treatments did not differ
      significantly in safety. These results clearly indicate that mianserin is
      effective in the prophylaxis of recurrent depressive episodes.

PMID- 8140907
TI  - Familial risk factors for adolescent suicide: a case-control study.
AB  - Sixty-seven adolescent suicide victims and 67 demographically matched living
      controls were compared as to family constellation, familial stressors and
      familial loading for psychopathology. Suicide victims were less likely to have
      lived with both biological parents, were more likely to be exposed to stressors
      such as parent-child discord, physical abuse and residential instability and
      showed greater familial loading for depression and substance abuse. Multivariate
      analyses showed that family history of both depression and substance abuse and
      lifetime history of parent-child discord were most closely associated with
      adolescent suicide. Children who are the offspring of parents with depression or
      substance abuse should be psychiatrically screened. Family interventions to
      decrease discord may also be helpful in decreasing the risk of adolescent
      suicide.

PMID- 8140908
TI  - Prevalence of panic disorder in mitral valve prolapse: a comparative study with a
      cardiac control group.
AB  - This study investigated the relationship between mitral valve prolapse (MVP) and
      panic disorder (PD), by comparing the prevalence of PD in 33 patients with MVP
      and 27 patients with haemodynamically insignificant atrial septal defect or
      patent ductus arteriosus. MVP was diagnosed using standard echocardiographic
      criteria and the presence of mental disorder was assessed blindly with the help
      of the Schedule for Affective Disorders and Schizophrenia. DSM-III criteria were
      used to diagnose PD. The two groups did not differ in age and sex; 12.1% of MVP
      patients and 3.7% of cardiac controls had PD (NS). Although the prevalence of PD
      in our sample of MVP patients was considerably higher than the prevalence of PD
      in the general population, this need not necessarily indicate a causal
      relationship between MVP and PD and may be due to studying a hospital-based
      sample. The absence of any significant difference in prevalence of PD between MVP
      patients and a carefully selected cardiac control group drawn from the same
      setting argues against any special relationship between PD and MVP.

PMID- 8140909
TI  - A cross-sectional study of glomerular function in 740 unselected lithium
      patients.
AB  - Creatinine clearance was estimated using a formulaic method from serum
      creatinine, age and sex in 740 unselected lithium-treated patients in
      southeastern Scotland. Psychiatric history and details of prescribing and
      monitoring of lithium treatment were obtained from existing case registers.
      Lithium treatment duration and glomerular filtration, controlling for the effects
      of age, were weakly related, but only in males. Cases who had been exposed to
      higher serum lithium concentrations had lower creatinine clearance than those
      maintained within therapeutic range. Of cases within the lowest quartile of renal
      function, proportionally more were supervised in general practice rather than at
      hospital clinics. Suggestions are made for the clinical practice of monitoring
      serum lithium concentrations and serum creatinine.

PMID- 8140910
TI  - A latent variable causal model of the quality of life and community tenure of
      psychotic patients.
AB  - Services are intended to maintain patients in the community while improving the
      quality of their lives. The purpose of this study was to determine the extent to
      which psychiatric patients' diagnoses, levels of autonomy, objective living
      conditions and degree of service utilization are associated with their perceived
      quality of life and, in turn, community tenure. A latent variable causal model
      was developed and tested using data from 152 schizophrenic and affective
      psychotic patients. Information was obtained using a semistructured interview, a
      quality of life scale, ratings on the Global Assessment Scale and patient
      hospital records. Results indicate that greater autonomy is significantly
      associated with greater perceived quality of life and that greater quality-of
      life ratings are associated with greater community tenure.

PMID- 8140911
TI  - Hysterical neurosis--a follow-up study.
AB  - Hysterical neurosis, though infrequently diagnosed in the West, is still one of
      the commonest mental disorders in India. In this study, 38 women with an index
      diagnosis of hysterical neurosis were evaluated after a period of 5 years; 63% of
      the patients remained totally asymptomatic. The premorbid hysterical personality
      alone showed significant relationship with the outcome.

PMID- 8140912
TI  - The prevalence of depressive symptoms and predisposing factors in an elderly
      Chinese population.
AB  - In a survey of elderly Chinese aged 70 years and over living in Hong Kong
      selected by stratified random sampling, the prevalence of depression was
      determined using the 15-item Geriatric Depression Scale using a cut-off point of
      8 (sensitivity 96.3% and specificity 87.5% for this population). Subjects with
      moderate to severe cognitive impairment (CAPE I/O score < or = 7) were excluded.
      There were 877 men and 734 women. The adjusted overall prevalence for this
      population was 29.2% for men and 41.1% for women. The prevalence increased with
      age in men and was higher in women than in men. Univariate analysis identified
      many factors in the following areas that were associated with depression:
      socioeconomic characteristics, functional ability, physical health and social
      support. Stepwise logistic regression identified 16 factors predictive of
      depression: socioeconomic characteristics, such as borderline living expenses and
      dissatisfaction with living arrangement; poor social support, such as absence of
      an informal carer when ill, few relatives to turn to, and infrequent contact with
      neighbours and friends; functional disability, as indicated by a Barthel Index <
      15, urinary incontinence and inability to do housework; and poor physical health-
      poor self perceived health, poor vision, difficulty with chewing, history of
      mental illness, frequent hospital admissions and increased level of symptoms such
      as poor memory, constipation and dizziness. Some of these factors may be amenable
      to intervention, and such measures may be important in reducing the high
      prevalence of depression in elderly people.

PMID- 8140914
TI  - [Internal medicine. The concept, limits, education].

PMID- 8140913
TI  - [Burn patients].

PMID- 8140915
TI  - [A multivariate analysis of the factors associated with the severity of chronic
      venous insufficiency].
AB  - Chronic Venous Insufficiency (CVI) affects a large proportion of individuals and,
      with the ageing of the population of Western Europe, its prevalence is expected
      to increase. Epidemiological data, particularly regarding risk factors, is scarce
      and controversial. The purpose of this study was to identify clinical factors
      that are associated with an increase in severity of CVI. Eighteen physicians
      observed 474 unselected patients with symptoms suggesting CVI. A multivariate
      model is forwarded in which age is a major risk factor. Other factors that are
      independently correlated with the severity of CVI are body weight, environmental
      heat, sedentariness, double heredity, high-dose oestrogen formulations, osteo
      articular disease of the lower limbs, presence of troncular varices, involvement
      of the internal saphena, lymphedema or history of thrombophlebitis. Since most
      studies do not adjust for age when testing for risk factors, this may be an
      important reason for the multiplicity of reported factors and the lack of
      consistency of their results.

PMID- 8140916
TI  - [2 days of drug dependence consultation in Portugal].
AB  - This paper reports the results of a survey of all State outpatient clinics for
      drug addiction in Portugal. Two consecutive days of consultations in November
      1992 were considered. The Health Ministry's SPTT--Service for Drug Addiction
      Prevention and Treatment--coordinates the activity of all the centres and
      promoted the inquiry. The main objective was to simultaneously evaluate the state
      of the population under treatment in what concerns the therapeutic methods used,
      their clinical costs and efficacy. This methodology may allow us to draw an
      accurate portrait of the Portuguese drug addiction public health program. We
      received 535 answers which we estimate to be two thirds of the consultations.
      Heroin abuse is the main problem in 91.3% of all cases plus 3.9% that associate
      heroin and cocaine abuse. Cannabis comes next with 2.1%, alcohol abuse with 0.8%
      and benzodiazepines with 0.5%. In what concerns the clinical results, 60% were
      abstinent: 15.1% were abstinent for longer than six months, 9.9% for longer than
      three months but less than six months, 19.8% were abstinent for less than that
      but longer than a month and 14.5% for longer than a week but less than a month.
      The main therapeutic approaches were psychotherapeutic in 54.1%,
      psychopharmacologic in 42.1% and socio-therapeutic in 2.3% of the cases. The
      author presents further data and discusses the results and their clinical
      implications.

PMID- 8140917
TI  - [The HELLP syndrome in pregnancy-related hypertension].
AB  - During a 5-year period, 13 cases of HELLP syndrome were seen in hypertensive
      patients in the Obstetrics Department, Santa Maria Hospital, Lisbon. In 7 cases
      the syndrome occurred antepartum and in 6 during early early puerperium;
      gestational age and clinical features were very different from case to case. Four
      cases of eclampsia and 2 cases of acute renal failure occurred in 5 patients;
      there were 2 intrauterine deaths. Maternal mortality was nil. HELLP syndrome
      always implicates an important hepatic involvement with deleterious effects on
      the clinical status of the patients. Since the syndrome is often diagnosed in the
      puerperium and major complications seen in our study group occurred in that
      period, we conclude that all hypertensive patients must be closely monitored
      during the first 48 hours after delivery.

PMID- 8140918
TI  - [The treatment of burn patients. What are the prospects for the northern area of
      Portugal?].
AB  - The AA studied the distribution of age, sex, aetiology, and destiny of the 173 in
      patients at the S. Joao Hospital (Central hospital that has no Burn Unit). In
      what concerns age, 38.1% are children less than 10 years old; the male/female
      ratio was 1.7:1. The fire and scalds are the most important aetiology. These
      findings are similar to those found in other countries (except in the Arabian
      Countries). Of these 99 burn patients have been treated in S. Joao Hospital, 71
      patients were sent to the Burn Unit of Prelada Hospital and 3 to the Burn Unit of
      Coimbra University Hospital. These findings were compared to a Burn Unit of a
      Spanish Hospital (Alicante) which has 18 beds for adults and children, normally
      interning 132 patients per year. As the WHO suggest one special bed per 30,000
      persons, we should be expected to have at least 110 beds for burn patients (we
      only have 9 beds at Prelada Hospital), the AA suggest the establishment of a Burn
      Unit at S. Joao Hospital, also due to the fact that is the only hospital that has
      a permanent emergency care for Plastic Surgery.

PMID- 8140919
TI  - [Burns. A retrospective study of the Burn Unit of the Hospital de Santa Maria].
AB  - A retrospective analysis was made concerning 291 admissions to the Burn Care Unit
      from June 1987 to March 1992, due to acute burns. Within that considered period
      of time there was a progressive increase in the number of admissions. Of the
      patients admitted, patients 177 men were and 144 women. The average age was 33.7
      years. The main etiology was thermal injury. The average time of admission was
      24.3 days. The mortality rate was 18%. The observer complications were mainly
      cutaneous and were seen on patients who were lately debrided.

PMID- 8140920
TI  - [Amandio Tavares].

PMID- 8140921
TI  - [Pure autonomic failure].
AB  - We present the case of a 64-year-old woman who, in the past 5 years, complained
      of constipation/diarrhea, hyposudoresis, xerostomia and xerophthalmia, dysuria
      and orthostatic hypotension. Cardiovascular reflexes analysis revealed
      sympathetic and parasympathetic failure. Norepinephrine was markedly reduced,
      both lying and after tilt. Norepinephrine infusion determined a significant rise
      in blood pressure, allowing the diagnosis of denervation hypersensitivity. The
      diagnosis of pure autonomic failure was made. Therapy with 9 alpha
      fludrocortisone and metoclopramide was initiated with marked and sustained
      symptomatic effect.

PMID- 8140922
TI  - [A recurrent intracardiac mass in a pregnant woman with the antiphospholipid
      antibody syndrome].
AB  - Clinical manifestations of the antiphospholipid syndrome result from
      thromboembolic phenomena that occur in all vascular territories. Cardiac
      manifestations frequently associated with this syndrome include valvular and
      myocardial lesions. We present a case report of primary antiphospholipid syndrome
      in a pregnant young woman with a right atrial mass detected by echocardiography.
      Its morphological characteristics presented problems in establishing differential
      diagnosis within atrial thrombus and atrial myxoma. This case was complicated by
      pulmonary embolism and recurrence of the mass within four months. Cardiac surgery
      was performed and two masses excised. Histopathological studies showed them to be
      thrombotic in nature.

PMID- 8140923
TI  - [Visceral leishmaniasis and HIV infection: the diagnostic and therapeutic
      problems].
AB  - We present the case of an HIV-seropositive drug addict patient whose
      seropositivity was unknown until admission to hospital, where he presented with a
      clinical picture of fever splenomegaly and weight loss. A diagnosis of visceral
      leishmaniasis was established. We stress the diagnostic difficulties well
      expressed in the need to repeat the bone marrow aspirate to detect the presence
      of leishmanias. The lack of response to conventional antimonial therapy is
      discussed as well as the role of pentamidine as an alternative therapy.

PMID- 8140924
TI  - [O2 generation during neuromelanin synthesis. The action of manganese].
AB  - The oxygen uptake during the reaction of dopamine autoxidation was studied and it
      was found that it may occur through two distinct oxidative pathways. One involves
      the univalent reduction of oxygen, forming the superoxide radical, the other
      involves a bivalent reduction which generates hydrogen peroxide. The detection of
      the univalent reaction was followed by the study of oxygen consumption, in the
      presence of cytochrome c. The detection of the bivalent reaction was made in the
      presence of catalase. It was found that manganese increases the oxygen uptake of
      the reaction, by increasing the production of both oxygen active forms. It seems
      probable that the neurotoxicity of this metal may be related with the increased
      production of activated oxygen in dopaminergic neurons, which undergo an
      oxidative stress.

PMID- 8140925
TI  - [Reflections on the curriculum in internal medicine].
AB  - The author approaches the problem of postgraduate training in internal medicine.
      He points out that apart from the classic internist, one must consider the
      internist working in intensive care units or with special vocation in medical sub
      specialties. He also approaches the relationship between internal medicine and
      medical sub-specialties as well as general practice, proposing a common trunk of
      two years for these branches of medical practice.

PMID- 8140926
TI  - Monitoring bone resorption in early postmenopausal women by an immunoassay for
      cross-linked collagen peptides in urine.
AB  - A new immunoassay using an ELISA approach for measuring urinary excretion of
      cross-linked N-telopeptides of type 1 collagen was evaluated as a specific
      measure of bone resorption. The assay was applied to 65 early postmenopausal
      women who participated in a placebo-controlled trial of the aminobisphosphonate,
      alendronate sodium. Eight blood and urine samples were collected over a 9 month
      interval. Baseline cross-linked peptide excretion varied from 26 to 216 pmol BCE
      (bone collagen/mumol Cr. Within-subject variability (CV) for cross-linked peptide
      excretion was 20.2% over the 9 months in placebo-treated subjects, substantially
      less than that observed for other biochemical markers of bone resorption: 45, 53,
      and 63% for fasting urinary calcium and hydroxyproline and 24 h urinary
      lysylpyridinoline (HPLC assay), respectively. Baseline cross-linked peptide
      excretion correlated significantly (p < 0.001) with baseline total urine
      lysylpyridinoline and serum osteocalcin, but not with the other biochemical
      markers. Initial peptide excretion also correlated inversely with lumbar spine
      bone mineral density at entry (r = -0.26, p < 0.05). Treatment for 6 weeks with
      alendronate produced a dose-dependent suppression of cross-linked peptide
      excretion (0 +/- 8, 29 +/- 6, 56 +/- 5, and 64 +/- 3% for 0, 5, 20, and 40 mg,
      respectively, p < 0.01 versus placebo for treatment effect), with a return toward
      pretreatment values during follow-up. Measurement of the urinary cross-linked N
      telopeptides of type I collagen by this new ELISA approach appears promising as a
      simple and reliable method to assess overall bone resorption.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8140927
TI  - Transcriptional activation of the human osteocalcin gene by basic fibroblast
      growth factor.
AB  - Basic fibroblast growth factor (bFGF) has been detected in bone cells and
      stimulates osteoblast proliferation; however, its role in the regulation of bone
      metabolism remains speculative. We demonstrated that the human osteocalcin
      promoter is activated by bFGF when transfected into rat osteoblastic (ROS 17/2.8)
      cells. This effect is concentration dependent, with a twofold induction at 10
      ng/ml detected after 20 h. The bFGF response is independent of both the 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3] and retinoic acid activation of the
      osteocalcin promoter. To identify the promoter sequences through which bFGF
      exerts its effect, we tested a series of promoter deletion constructs for their
      response to bFGF. Deletion of the upstream region between -673 and -588 bp
      results in a significant loss of induction. Gel-shift analysis demonstrates that
      proteins present in ROS 17/2.8 nuclear extracts bind specifically to these
      sequences. This region alone was unable to confer the bFGF response on a minimal
      osteocalcin or an heterologous promoter. However, sequences between -678 and -476
      bp, which also includes the vitamin D response element (VDRE), were able to
      confer bFGF inducibility on both a minimal osteocalcin and a heterologous
      promoter. These data suggest that induction of the human osteocalcin promoter by
      bFGF requires the interaction of more than one sequence element.

PMID- 8140928
TI  - Effect of long-term tamoxifen therapy on cancellous bone remodeling and structure
      in women with breast cancer.
AB  - The effects of long-term tamoxifen therapy on bone remodeling were studied in 41
      women with breast cancer, 22 treated with tamoxifen for a minimum of 15 months
      (mean 33) and 19 untreated. Transiliac crest bone biopsies were obtained and a
      comprehensive histomorphometric analysis performed using a semiautomatic image
      analysis system. There were no statistically significant differences between the
      two groups in bone area, osteoid perimeter and area, or osteoid width. Mineral
      appositional rate, adjusted appositional rate, and mineralization lag time were
      also similar in the two groups; however, tissue-based bone formation rate was
      significantly lower in the tamoxifen-treated women (p = 0.05) and the remodeling
      period significantly longer (p < 0.05). Mean and maximum resorption cavity depth
      and cavity area were significantly reduced in the tamoxifen-treated patients
      compared to the untreated patients (p < 0.01, p < 0.01, and p < 0.03,
      respectively). Calculated and directly measured indices of cancellous bone
      structure were similar in the two groups, although the data indicated a trend
      toward greater connectedness in the tamoxifen-treated group. These data indicate
      that tamoxifen does not exert an antiestrogenic effect on bone remodeling in the
      human and are consistent with a weak estrogenic effect.

PMID- 8140929
TI  - Role of chondroitin sulfate glycosaminoglycans in mineralizing osteoblast-like
      cells: effects of hormonal manipulation.
AB  - A monoclonal anti-chondroitin sulfate antibody (CS-56) that recognizes native
      chondroitin sulfate glycosaminoglycans (CSGAG) was used to quantify changes in
      CSGAG labeling levels in mineralizing human fetal osteoblast-like cell
      multilayers up to 40 days postconfluence. In control cultures, mean labeling of
      CSGAG increased in nonmineralized areas from around eight gold probes per micron
      2 (gpm) at 20 days to 26 gpm at 40 days. Labeling was markedly increased in the
      mineralized tissue, to 560 gpm at 30 days and 580 gpm at 40 days. In beta
      glycerophosphate-treated cultures, the mineralized areas were increased and
      appeared earlier (20 days) than in the control cultures. In these cultures, mean
      CSGASG labeling increased in nonmineralized areas from around 5 gpm at 20 days to
      26 gpm at 30 days and was further increased in mineralized areas to 270 gpm at 20
      days and 298 gpm at 30 days. Mineralization was not noted in cultures treated
      with 10(-8) M 1,25-dihydroxyvitamin D, and CSGAG labeling remained low (< 5 gpm)
      during the study period. These results indicate that an increase in
      immunoreactive CSGAG is associated with mineralization in this culture system.
      One possible interpretation of these findings is that proteoglycan molecules or
      at least their CSGAG side chains may be involved in the mineralization process.

PMID- 8140930
TI  - Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy
      substrate utilization and mineral metabolism in the chick.
AB  - An experiment was designed to test part of the hypothesis that physiologic
      amounts of dietary boron enhance utilization of or, alternatively, compensate
      for, inadequate concentrations of active vitamin D metabolites to normalize
      energy substrate utilization and mineral metabolism. Day-old cockerel chicks were
      fed a ground corn, high-protein casein, corn oil-based diet (< or = 0.18 mg B/kg)
      supplemented with physiologic amounts of boron (as orthoboric acid) at 0 (non
      PSB) or 1.4 (PSB) mg/kg and vitamin D3 (as vitamin D3 powder in corn endosperm
      carrier) at 3.13 (inadequate, IVD) or 15.6 (adequate, AVD) micrograms/kg. After
      26 days, IVD decreased food consumption and plasma calcium concentrations and
      increased plasma concentrations of glucose, beta-hydroxybutyrate, triglycerides,
      triiodothyronine, cholesterol, and alkaline phosphatase activity. In the IVD
      chicks, PSB returned plasma glucose and triglycerides to concentrations exhibited
      by the AVD chicks and increased food consumption in both IVD and AVD chicks.
      Histologic findings suggested that PSB enhanced maturation of the growth plate. A
      ninefold increase in dietary boron yielded only a two-fold increase in plasma
      boron concentration and no increase in femur boron concentration, which suggests
      that boron is under homeostatic control. The findings suggest that boron acts on
      at least three separate metabolic sites because it compensates for perturbations
      in energy substrate utilization induced by vitamin D3 deficiency, enhances major
      mineral content in bone, and, independently of vitamin D3, enhances some indices
      of growth cartilage maturation.

PMID- 8140931
TI  - Characterization of the stromal osteogenic cell line MN7: mRNA steady-state level
      of selected osteogenic markers depends on cell density and is influenced by 17
      beta-estradiol.
AB  - The steady-state mRNA levels of different osteogenic markers and their modulation
      by 17 beta-estradiol in the murine osteogenic cell line MN7 during proliferation
      and differentiation in vitro were examined. mRNA of collagen type I, osteopontin,
      bone morphogenetic protein 2, plasminogen activator inhibitor 1, alkaline
      phosphatase, and osteocalcin were isolated from MN7 cultures grown for 7, 11, 14,
      and 17 days. Northern blot analysis revealed steady-state transcript levels
      depending on MN7 cell density. The order of appearance of Col I, OP, ALP, and OC
      resembled the pattern of gene expression observed during osteoblast maturation in
      vitro. Furthermore, PAI-1 steady-state transcript levels peaked during
      subconfluence (day 11) but BMP-2 RNA levels reached their maximum after the
      culture had become confluent. 17 beta-Estradiol showed a dose-dependent
      stimulation of the different osteoblast-related transcripts present in a
      subconfluent MN7 culture at the time of analysis. Furthermore, the effects of 17
      beta-estradiol (17 beta E2) at different time points of MN7 growth varied
      according to cell density. 17 beta E2 added to subconfluent MN7 cultures
      modulated the transcript level in a negative way, but RNA levels of the
      investigated osteogenic markers in confluent cultures were stimulated with 100 nM
      17 beta-estradiol. No effect of 17 beta-estradiol on proliferation was detected.
      The present studies have revealed differential osteoblast gene expression related
      to MN7 cell proliferation and differentiation in vitro and emphasize the
      importance of 17 beta E2 in the regulation of growth of this preosteoblastic cell
      line in vitro.

PMID- 8140932
TI  - Synthetic peptide containing Arg-Gly-Asp inhibits bone formation and resorption
      in a mineralizing organ culture system of fetal rat parietal bones.
AB  - The role of integrins, cell surface receptors involved in cell adhesion to the
      matrix, was studied in a mineralizing organ culture system. Integrin-mediated
      cell attachment to matrix proteins has been shown to depend partially on the
      amino acid sequence Arg-Gly-Asp (RGD), present in the extracellular matrix
      proteins. Therefore, the effect of RGD peptides on bone formation and resorption
      was studied in the mineralizing organ culture system derived from 18 day fetal
      rat parietal bones. Addition of 0.1-50 microM GRGDSPK to bones cultured for 4
      days inhibited mineralization in a dose-dependent manner as determined by
      measuring calcium content and % bone/unit area of tissue. A maximal decrease in
      calcium content and % bone/unit area of 32.5 and 42.9%, respectively, was found
      with 50 microM GRGDSPK. With 10 and 50 microM GRGDSPK, bone morphology was
      dramatically altered, with a disruption of osteoblast and mineralized matrix
      organization. To assess the effect of the peptides on bone resorption, fetal
      bones were prelabeled in vivo with 45Ca and resorption was stimulated in vitro
      with parathyroid hormone in the presence or absence of the peptide. A significant
      decrease in 45Ca release was found with 10 and 50 microM GRGDSPK. Osteoclast
      number was also significantly decreased on the bone surface. The peptide was not
      cytotoxic, since no effect on DNA content, dry weight, or collagen synthesis was
      found. GRADSP, a control peptide, had no significant effect on mineralization,
      resorption, or other parameters of bone growth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140933
TI  - Bone response to alternate-day mechanical loading of the rat tibia.
AB  - Mechanical loading of the living skeleton influences bone formation, mass, and
      strength. The primary purpose of the present study was to examine the influence
      of different loading schedules (days/week) on the bone response to external
      loading using an in vivo rat tibia four-point bending model. Three studies were
      conducted to (1) characterize the loaded region, (2) examine the variation of the
      response within the loaded region, and (3) test the response to different loading
      schedules. In all studies adult female retired breeder Sprague-Dawley rats were
      used (6 months, 285 g). First, the location of the loaded region during four
      point bending was determined by radiogrammetry of 7 rats. Second, 5 rats were
      externally loaded for 8 of 10 days at 31 N, 36 cycles, and 2 Hz (1349 +/- 244 mu
      epsilon). The extent of labeled (forming) periosteal and endocortical surface in
      the loaded region was compared both among four serial sections from the same
      tibia and between the loaded and the contralateral tibiae. Finally, 50 rats were
      randomized into five groups: two nonloaded, control and sham, and three loaded,
      alternate day, Monday, Wednesday, and Friday, and daily. The rats were externally
      loaded for 3 weeks at 35 N, 36 cycles, and 2 Hz (1533 +/- 308 mu epsilon). The
      tibia and fibula were studied for labeled surfaces and mineral apposition rate.
      For adult female rats with tibial length 39 mm, the loaded region was located 3.5
      14 (+/- 0.7) mm proximal to the tibia-fibula junction (TFJ).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8140934
TI  - Proton-induced physicochemical calcium release from ceramic apatite disks.
AB  - When bone is cultured in acid medium there is net calcium efflux (JCa) and proton
      influx (JH) relative to the mineral. The acid medium appears to induce
      physicochemical mineral dissolution as well as cell-mediated bone resorption. To
      determine the independent effect of acid medium on physicochemical dissolution,
      we utilized cell-free synthetic ceramic apatite (CAP) disks, which contain
      carbonate (5.5%) in an apatite structure chemically similar to mammalian bone.
      CAP disks were cultured in control (Ctl, pH approximately equal to 7.44) or acid
      (Met, pH approximately equal to 7.11) medium for 48 h and compared to similarly
      treated neonatal (4-6 days old) mouse calvariae. Medium was changed and analyzed
      at 3, 24, and 48 h. At 3, 24, and 48 h there was significantly greater JCa from
      the CAP disks and calvariae incubated in Met compared to Ctl; over the entire 48
      h time period there was a greater progressive increase in JCa from the CAP disks
      than the calvariae incubated in Met. There was no significant JCa at 3, 24, or 48
      h from CAP disks or calvariae incubated in Ctl. At 3 h there was significantly
      greater JH into the CAP disks and calvariae incubated in Met compared to Ctl; JH
      was greater into the CAP disks than the calvariae. Utilizing a synthetic model of
      bone mineral we demonstrated that acid medium induces physicochemical calcium
      efflux and proton influx relative to the mineral.

PMID- 8140935
TI  - Effect of the bisphosphonate risedronate on bone metastases in a rat mammary
      adenocarcinoma model system.
AB  - Risedronate (NE-58095) is a third-generation bisphosphonate with very potent
      antiresorptive activity but few toxic effects. The purpose of this work was to
      evaluate the effect of risedronate treatment on bone metastases produced in a rat
      breast cancer model. Berlin Druckrey IV rats inoculated with ENU1564 mammary
      adenocarcinoma cells were treated daily with risedronate or a saline placebo.
      Survival times, dictated by extraskeletal metastases (lung, heart, and brain),
      were not affected by risedronate treatment. Risedronate-treated animals had
      skeletal changes associated with decreased remodeling of bones undergoing
      endochondral ossification, most prominently affecting the appendicular skeleton.
      Despite the skeletal alterations induced by the treatment, the distribution of
      bone metastases throughout the surveyed skeletal sites was similar for treated
      and untreated animals. Bone metastases were enumerated in histologic sections of
      distal femur, spine, and skull. Tumor size was estimated from area measurements
      obtained from histologic lesions in distal femoral metaphyses and vertebral
      bodies. A greater number of treated rats had no bone metastases in any of the
      examined sections (30 versus 16.1% of untreated rats). Multiple bone metastases
      were observed less frequently in treated rats (33.3 versus 71% of untreated
      rats). Treated rats had fewer observed bone metastases in each examined site than
      untreated rats (p < or = 0.025). Mean tumor areas in femora and vertebrae were
      smaller in treated rats (p < or = 0.05), due to the less frequent presence of
      very large lesions. In untreated animals, osteoclasts appeared to be active at
      the tumor/bone interface and osseous structures were often completely replaced by
      expanding tumors. In contrast, metastases in treated animals caused less
      disruption of skeletal histoarchitecture. The apparent lack of osteoclastic
      activity and retention of bone within lesions suggested a decreased contribution
      of osteoclasts to the bone resorptive process. An in vivo immunohistochemical
      cell proliferation assay failed to reveal differences in the percentage of
      dividing tumor cells in bone metastatic sites in treated versus untreated
      animals. The results demonstrate significant effects of risedronate treatment on
      the incidence and size of observed skeletal metastases in this model.

PMID- 8140936
TI  - Temporal changes in matrix protein synthesis and mRNA expression during
      mineralized tissue formation by adult rat bone marrow cells in culture.
AB  - To characterize the bone-like tissue produced by rat bone marrow cells (RBMC)
      from young adult femurs, the synthesis of bone proteins and the expression of
      their mRNA were studied in vitro. RBMC plated at a density of 5 x 10(3) cells/cm2
      and grown in the presence of 10(-8) M dexamethasone (Dex) and 10 mM beta
      glycerophosphate (beta-GP) produced mineralized bone nodules, which were first
      evident at day 3 and increased markedly to day 13. However, in the absence of
      dexamethasone, few mineralized nodules were observed. The formation of
      mineralized nodules was reflected by the uptake of 45Ca, which also increased
      markedly to day 13. Analysis of bone protein expression by Northern and slot-blot
      hybridizations revealed an increase in mRNA levels of collagen type I (Col I),
      osteonectin/SPARC (ON), alkaline phosphatase (ALP), osteopontin (OPN), bone
      sialoprotein (BSP), and osteocalcin (OC) during the formation of mineralized
      nodules. Whereas the Col I, ON, ALP, and OPN mRNAs were expressed before the
      formation of mineralized nodules was evident and were also expressed at various
      levels in the absence of Dex, the expression of BSP and OC mRNA was induced in
      the bone-forming cultures. The expression of BSP mRNA was correlated temporally
      with bone tissue formation, reaching maximal levels on day 16. In contrast, OC
      mRNA was expressed later and, following induction, increased over the 28 day
      culture period. Production of matrix proteins during the rapid formation of the
      bone tissue appeared to reflect the levels of the respective mRNAs. However,
      whereas some of the collagen and almost all of the SPARC were secreted into the
      culture medium, virtually all of the OPN and most of the BSP were extracted from
      the mineralized tissue matrix with EDTA. Some OPN and BSP were present in the
      medium, especially early in the culture, and a significant amount of BSP was also
      found associated with the collagenous tissue matrix. These studies point to the
      importance of Col I, ALP, OPN, and BSP, but not ON or OC, in the initial
      formation of bone tissue.

PMID- 8140937
TI  - Use of a rat model for the simultaneous assessment of pharmacokinetic and
      pharmacodynamic aspects of bisphosphonate treatment: application to the study of
      intravenous 14C-labeled 1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1
      bisphosphonate.
AB  - Bisphosphonates are drugs that suppress osteoclast-mediated bone resorption and
      are used with increasing frequency in the treatment of skeletal disorders.
      Therapeutic regimens are largely based on pharmacodynamic information because of
      difficulties in obtaining and interpreting pharmacokinetic data. We describe here
      the application of a permanently cannulated rat model, previously used in other
      areas of endocrine research, to the simultaneous study of pharmacokinetic and
      pharmacodynamic properties of the newly developed bisphosphonate EB-1053 [1
      hydroxy-3-(1-pyrrolidinyl)propylidene-1,1-bisphosphonate]. Two groups of five
      rats each received daily intravenous injections of [14C]EB-1053 (0.025 and 0.1
      mg/day, respectively); a third group (n = 7) received only normal saline
      injections and served as control. Treatment was given for at least 20 days. A
      fourth group (n = 3) received IV injections of the bisphosphonate on three
      separate occasions. Following IV administration, EB-1053 was rapidly cleared from
      the circulation. Urinary excretion of radioactivity reached about 55% of the
      daily administered dose within 48 h and remained at this level during the whole
      treatment period, indicating continuing retention of the bisphosphonate. Bone
      resorption, assessed biochemically as the hydroxyproline to creatinine ratio in
      urine, was suppressed effectively with both doses used. Suppression reached a
      maximum around day 4 and remained at the same level until the end of treatment.
      Accumulation of the bisphosphonate in the skeleton was therefore not associated
      with a cumulative effect on bone resorption. This strongly suggests that in
      treatment planning a distinction should be made between surface-bound and hence
      biologically active bisphosphonate from the drug which is incorporated in bone
      during bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140938
TI  - Comparison of the effects of 3,5,3'-triiodothyroacetic acid and triiodothyronine
      on bone resorption in cultured fetal rat long bones and neonatal mouse calvariae.
AB  - Thyroid hormones can stimulate bone resorption both directly and indirectly by
      increasing endogenous prostaglandin (PG) synthesis. Because 3,5,3'
      triiodothyroacetic acid (Triac, Tiratricol) can bind to nuclear thyroid hormone
      receptors with high affinity, we compared the effects of Triac and 3,5,3'
      triiodothyronine (T3) on bone resorption. 45Ca release was measured at 2, 5, and
      8 days from 19-day-old-fetal rat long bones in the presence or absence of
      calcitonin, indomethacin, aphidicolin (APC), cortisol, or interleukin-1 receptor
      antagonist (IL-1ra). Both Triac and T3 stimulated 45Ca release in a dose
      dependent manner. The maximal treated/control ratio (T/C) for Triac (10(-7) M)
      was 1.6 +/- 0.1 at 2 days and 2.5 +/- 0.1 at 5 days and, for T3 (10(-7) M), 1.5
      +/- 0.1 at 2 days and 2.6 +/- 0.1 at 5 days. These responses were smaller and
      slower than that to PTH. Significant stimulation of resorption was observed at
      10(-8), 10(-9), and 10(-10) M for Triac but only at 10(-8) and 10(-9) M for T3.
      Indomethacin (10(-6) M) and IL-1ra (1 microgram/ml) did not decrease the effects
      of Triac or T3. In contrast, calcitonin (10(-9) M), APC (30 microM), and cortisol
      could all block the response to these hormones. These results indicated that the
      resorptive responses were not mediated by endogenous PG or IL-1 but were
      osteoclast mediated and dependent on DNA synthesis, suggesting that these
      hormones acted by stimulating replication of osteoclast precursors or other
      supporting cells. Thyroid hormones were less effective in 7-day-old neonatal
      mouse calvariae.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8140939
TI  - Characterization of immunoreactive forms of human osteocalcin generated in vivo
      and in vitro.
AB  - Three monoclonal antibodies recognizing the 5-13, 25-37, and 43-49 sequence of
      the human osteocalcin were used in competitive and two-site radioimmunoassays
      (RIA) to characterize specifically various immunoreactive forms of circulating
      human osteocalcin. The intact molecule accounts for 36% of total in normals (2.6
      nM), 46% in patients with osteoporosis (3.1 nM), and 26% in chronic renal failure
      (6.9 nM). Four fragment were detected in addition to the intact molecule in the
      serum of healthy adults and patients with metabolic bone disease. N-terminal,
      mid, and mid C-terminal fragments were present in minute amounts (each accounting
      for 5-14% of the total circulating osteocalcin immunoreactivity). In contrast,
      the N-terminal midfragment, probably resulting from the cleavage around amino
      acids 43-44, represents about 30% (2 nM) of the total osteocalcin immunoreactive
      level in normals and patients with osteoporosis and up to 50% (13 nM) in patients
      with chronic renal failure. This large N-terminal midfragment, representing 75
      80% of the intact osteocalcin level, is not lower when the plasma assay is
      performed immediately after sampling (within 20 minutes at 4 degrees C with
      proteinase inhibitors), indicating that it circulates in vivo. In addition, this
      fragment was detected in the supernatant of osteoblastic cells, representing
      about 28% of the intact peptide. Levels of N-terminal midfragment were not
      changed after treatment of patients with metabolic bone disease (Paget's disease,
      reflex sympathetic dystrophy, fibrous dysplasia, and osteoporosis) by
      bisphosphonate, suggesting that it is not released during bone resorption. The
      osteocalcin level measured with the two-site immunoradiometric assay specific for
      the intact molecule or with a conventional bovine RIA was rapidly decreased after
      incubation of serum at room temperature (-20 and -15%, respectively, after 3 h),
      whereas the total level of intact osteocalcin plus N-terminal midfragment was not
      changed. Intact osteocalcin loss can be partially avoided by proteinase
      inhibitors and by incubating serum at 4 degrees C. In conclusion, we
      characterized multiple immunoreactive forms of osteocalcin that circulate in
      addition to the intact molecule, none of them being specifically altered in
      osteoporosis. The N-terminal midfragment circulates in a large amount, probably
      resulting from cleavage of the intact molecule in the circulation and/or at
      peripheral sites. These fragments can also be generated in vitro by proteolytic
      degradation of the intact molecule. To obtain reliable intact osteocalcin values
      but also reliable levels measured with conventional competitive RIA, careful
      control of the sampling conditions is warranted.

PMID- 8140940
TI  - Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended
      observations and additional analysis.
AB  - In a 4 year clinical trial in 202 postmenopausal osteoporotic women receiving NaF
      at 75 mg/day or placebo (both groups received supplementary calcium at 1500
      mg/day), we found (N Engl J Med 322:801, 1990) that NaF increased bone mineral
      density in the lumbar spine (LS-BMD) substantially but did not decrease vertebral
      fracture rate (VFR), and it increased the nonvertebral fracture rate. Additional
      analyses and extended observations are now available on 50 women from the NaF
      group followed for up to 6 years of treatment. In these women, LS-BMD increased
      linearly over the 6 years (median rate, 8.7%/year or 0.063 g/cm2/year). Because
      during the 4 year trial the NaF dosage was decreased (because of side effects) in
      54 of the 101 women randomized to NaF, dose-response relationships could be
      evaluated. For the entire study population, serum F level correlated directly
      with increase in LS-BMD (r = 0.61, P < 0.001). When individual person-years of
      observation were grouped by deciles of LS-BMD, VFR (per 100 person-years)
      decreased to a nadir of 24 as mean LS-BMD for the group increased from 0.6 to 1.2
      g/cm2 and then doubled to 52 in the group with mean LS-BMD of 1.6 g/cm2.
      Multivariate analyses and inspection of three-dimensional plots revealed a
      complex pattern in which VFR was influenced by interaction of several variables.
      When the effects of LS-BMD, changes in LS-BMD, and serum F were assessed
      simultaneously, VFR was seen to decrease with increasing LS-BMD except when the
      higher LS-BMD was associated with rapid rate of increase in LS-BMD or a large
      increase from baseline serum F. For some patients (noncompliers or
      nonresponders), serum F or LS-BMD failed to increase. Thus, it is possible that
      lower dosages of NaF produce moderate decreases in VFR.

PMID- 8140941
TI  - Course of bone mass during and after hormonal replacement therapy with and
      without addition of nandrolone decanoate.
AB  - A total of 33 women with postmenopausal osteoporosis were matched pairwise by
      age, years since menopause, and body mass index and randomized to receive either
      cyclic estrogen-progestagen replacement treatment (group 1) or the same treatment
      plus nandrolone decanoate (ND; group 2). Both groups were treated during 3 years
      and subsequently followed for another year off treatment. A year after cessation
      of the treatment the distal forearm bone mineral content in group 2 was
      significantly higher than that in group 1. Bone mass measurements in the axial
      skeleton already showed a significant difference in favor of group 2 after 3
      years treatment, which persisted during the year off treatment. The decline in
      lumbar bone mineral mass and density in the 1 year off treatment was similar in
      both groups. Correction for body mass did not change these results. Bone turnover
      parameters did not show significant differences between the two groups after
      cessation of treatment. A higher muscle mass, induced by ND, could partly explain
      the differences between the groups since even 1 year after treatment was stopped
      an increased serum creatinine level was still observed in group 2.

PMID- 8140942
TI  - Development of the rat spinal cord: immuno- and enzyme histochemical approaches.

PMID- 8140943
TI  - Structural and thermodynamic aspects of the hydrophobic effect.
AB  - From analyses of the solvation structure around HS solutes for HS solvents and
      various water models by the RISM integral equation method, the following
      conclusions are drawn: 1) Water has more small cavities than HS solvents, which
      makes it easier for water to accommodate small solutes with a radius less than
      about 1A. 2) With increasing solute radius from 0 to 3A, the average orientation
      of hydrating water varies from an inward to an outward orientation, which shows
      that some reorganization of water occurs in response to the change in solute
      size. 3) The hydration structure is formed as a network structure due to H
      bonding interactions between water molecules being supported by the cooperation
      of repulsive forces between solute and water. Repulsive interactions of not only
      O atoms but also H atoms with solute are essential to the formation of such
      hydration structure. With regard to the physical mechanism of the hydrophobic
      effect, the following is concluded from an analysis of the physical meaning of
      the basic formula for the free energy of cavity formation: 4) It is predicted
      from the scaled particle theory that the solvent exclusion effect caused by the
      introduction of solute into solvent is an important factor of the hydrophobic
      effect. 5) The large negative transfer entropy at room temperature characteristic
      of the hydrophobic hydration results primarily from the decrease in the
      configuration entropy of water due to the solvent exclusion effect. 6) The
      structuralization of hydrating water results in exactly compensating changes in
      enthalpy and entropy, and a large positive change in heat capacity. As a result,
      the hydrophobic effect is dominated by the entropy effect at room temperature,
      while it is driven by enthalpy at temperatures higher than 110 degrees C. 7)
      Hydrating water is energetically similar to bulk water, and the term "highly
      structured" is not appropriate to describe it. The following descriptions can be
      made on estimating the free energy of transfer of biomolecules from gas or
      organic-liquid phase to water: 8) Derivation of the basic formula for the
      transfer free energy of solute with variable conformation was presented and
      physical meanings of the contributions to it were explained. 9) Applying the
      formula to the transfer of 40 organic molecules from gas phase to water, the two
      best models for diving all the constituent atoms into several hydration
      thermodynamically independent groups and the atomic hydration parameters of
      respective groups were determined.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8140944
TI  - The mechanism of accumulation of high levels of vanadium by ascidians from
      seawater: biophysical approaches to a remarkable phenomenon.

PMID- 8140945
TI  - Equilibrium muscle crossbridge behavior: the interaction of myosin crossbridges
      with actin.
AB  - The interaction of myosin crossbridges with actin under equilibrium conditions is
      reviewed. Similarities and differences between the weakly- and strongly-binding
      interactions of myosin crossbridges with actin filaments are discussed. A
      precise, narrow definition of weakly-binding crossbridges is given. It is
      postulated that the fundamental difference between the weakly- and strongly
      binding equilibrium interaction of crossbridges with actin is that the
      crossbridge heads are mobile after attachment in the first case but not in the
      second. It is argued that because the weakly-binding crossbridge heads are mobile
      after attachment, the heads appear to function independently of each other. The
      lack of head mobility in attached strongly-binding crossbridges makes the
      strongly-binding crossbridge heads appear to act cooperatively. This model of the
      strongly-binding crossbridge gives an explanation for two important and otherwise
      unexplained observations. It explains why the rate constant of force decay after
      a small stretch is a sigmoidal function of nucleotide analogue concentration, and
      why, in the presence of analogues or in rigor, the rate constant of force decay
      after a small stretch is often significantly slower than the rate constant for
      myosin subfragment-1 detachment from actin in solution. The model of the weakly
      binding crossbridge accurately describes the behavior of the myosin-ATP
      crossbridge.

PMID- 8140946
TI  - The mechanism of intracellular Ca2+ oscillation and electrical bursting in
      pancreatic beta-cells.

PMID- 8140947
TI  - Functional biomimics for copper proteins involved in reversible O2-binding,
      substrate oxidation/oxygenation and nitrite reduction.

PMID- 8140948
TI  - Functional mimics of vanadium enzymes.

PMID- 8140949
TI  - Functional non-heme iron metalloenzyme model systems.

PMID- 8140950
TI  - Porphyrins and metalloporphyrins in synthetic bilayer membranes.

PMID- 8140951
TI  - Fe/S and Fe/Mo/S clusters as speculative models for the metal centers in uncommon
      Fe/S proteins and the Fe/Mo protein of the nitrogenases.

PMID- 8140952
TI  - Role of vascular endothelial abnormalities in clinical medicine: atherosclerosis,
      hypertension, diabetes, and endotoxemia.

PMID- 8140953
TI  - Molecular genetic studies of the adenoma-carcinoma sequence.
AB  - During the past decade, a great deal of progress has been made toward identifying
      some of the genetic alterations that underlie human cancer development in
      general, and colorectal cancer in particular. It is now clear that mutations in
      both oncogenes and tumor suppressor genes have an important role in the process.
      However, much work lies ahead before a complete understanding of the pathogenesis
      of colorectal tumors will be obtained. It seems reasonable to predict that
      additional oncogenes and tumor suppressor genes with important roles in
      colorectal cancer remain to be identified. Characterization of the function of
      these genes in normal and neoplastic cell growth will be crucial. Unfortunately,
      we know little about the functions of the oncogenes and tumor suppressor genes
      already implicated in colorectal cancer. Undoubtedly, it will be crucial to
      understand the role of environmental and dietary influences on the nature and
      rate of mutations in colorectal tumors. Little is known about the relative
      significance of each of the various inherited and somatic mutations to the cancer
      phenotype. Moreover, although some preliminary studies have suggested possible
      clinical applications of the genetic studies to improved diagnosis and management
      of patients at risk of and harboring colorectal cancer, the scope and
      significance of the observations thus far are limited. Nevertheless, an
      optimistic view is that future molecular genetic studies not only will yield
      insights into the molecular basis of colorectal cancer, but also will improve the
      care of patients with colorectal tumors.

PMID- 8140954
TI  - Sexually transmitted diseases: advances in diagnosis and treatment.

PMID- 8140955
TI  - Body fluid volume regulation in health and disease.
AB  - The unifying hypothesis of body fluid volume regulation explains the renal
      handling of sodium and water in health and in various disease states associated
      with edema formation and no intrinsic renal parenchymal disease. According to
      this hypothesis, underfilling of the arterial vascular compartment, resulting
      from either a decrease in cardiac output or peripheral arterial vasodilation,
      initiates a sequence of events that results in activation of the sympathetic
      nervous and renin-angiotensin-aldosterone systems and the nonosmotic release of
      AVP. Activation of these neurohormonal vasoconstrictor systems causes diminished
      renal hemodynamics and renal sodium and water retention that persist despite an
      increase in total extracellular and blood volume. In edematous patients, a
      vasoconstrictor-mediated increase in proximal tubular sodium reabsorption results
      in diminished sodium delivery to the distal tubular sites of action of
      aldosterone and ANP; this explains the failure of such patients to escape from
      the sodium-retaining effects of aldosterone and the resistance to the natriuretic
      and diuretic effects of ANP. In pregnancy, an early decrease in systemic vascular
      resistance associated with activation of the neurohormonal vasoconstrictor
      systems precedes the normal expansion of blood and plasma volumes and is
      consistent with the arterial underfilling hypothesis. The loss of this peripheral
      vasodilatory response in some pregnancies may contribute to the development of
      preeclampsia and eclampsia.

PMID- 8140956
TI  - Therapy of acute and chronic viral hepatitis.
AB  - Viral hepatitis comprises five different diseases caused by five different viral
      agents: hepatitis A, B, C, D, and E virus. All five forms can cause acute
      hepatitis, only hepatitis B, C and D can cause chronic hepatitis. Alpha
      interferon has been shown to be effective in inducing sustained remissions in all
      three forms of chronic viral hepatitis. Its efficacy in acute viral hepatitis has
      not been documented, although preliminary results suggest that interferon may
      decrease the chronicity rate of acute hepatitis C. In chronic hepatitis B, alpha
      interferon therapy with 5 mu daily or 10 mu three time weekly for 16 weeks will
      induce a long-term remission in disease with loss of HBV DNA and HBeAg from serum
      in 25% to 40% of patients and ultimately, a loss of HBsAg in approximately half
      of the responders. Patients likely to respond are those with high initial serum
      aminotransferases and low levels of HBV DNA. In chronic hepatitis C, therapy with
      3 to 5 mu of alpha interferon 3 times weekly for 24 to 48 weeks will induce a
      temporary remission in disease with loss of HCV RNA from serum, fall of
      aminotransferases into the normal range and improvement in liver histology in 50%
      of patients and a sustained remission persisting after therapy is stopped in 25%
      of patients. Patients with a short duration of disease and without cirrhosis are
      the most likely to respond. Unfortunately, there are no completely reliable means
      of predicting which patients are likely to respond to interferon and which of
      these will have a lasting response. In chronic hepatitis D, a prolonged course of
      alpha interferon given in doses of 3 to 5 mu daily or 9 to 10 mu three times
      weekly results in remission in disease as marked by loss of HDV RNA from blood
      and fall of aminotransferases into the normal range in up to 50% of patients.
      Unfortunately, this response is rarely sustained after treatment unless HBsAg
      becomes negative, which occurs in only a small number of patients. Despite the
      benefits of alpha interferon therapy in many patients with chronic viral
      hepatitis, several shortcomings of this therapy are evident: less than 50% of
      patients respond, side effects can be problematical, and some patients are not
      appropriate for therapy. Thus, interferon is not indicated for patients with
      advanced cirrhosis or for those who are severely immunosuppressed. Alpha
      interferon is an important first step in therapy for chronic viral hepatitis, but
      further approaches are needed to increase its efficacy and safety.

PMID- 8140957
TI  - Emerging concepts in the management of vasculitic diseases.

PMID- 8140958
TI  - Human immunodeficiency virus and acquired immunodeficiency syndrome: an update.
AB  - Research progress in the understanding of HIV and its effects on the human immune
      system continues at a rapid pace. Such research is yielding new ideas for
      chemotherapeutic agents, immunologic stimulators and modifiers, and potential
      vaccines. Clinical trials to test these approaches are under way. Despite the
      accomplishments, the epidemic progresses unchecked, resulting in continued
      suffering and death and enormous demands on the health care system of many
      nations. Clinicians have had to deal with new and difficult opportunistic
      infections. Yet advances in the treatment and prevention of these illnesses have
      benefited many AIDS victims. In the United States, the AIDS epidemic is now
      concentrating in the inner cities, involving injection drug users, minorities,
      heterosexuals, women and their offspring. In the developing world, AIDS continues
      to be predominantly a heterosexually transmitted disease, where more than one
      third of prostitutes in central African cities are infected. The major burden of
      the AIDS epidemic in the remainder of this and the next century will be in India
      and Southeast Asia, again predominantly via heterosexual spread. A great deal is
      now understood concerning the life cycle of HIV. More light has been shed on the
      interaction of HIV and CD4+ T cells, the cellular and viral factors involved in
      viral expression vs. latency, the function of the viral regulatory and structural
      proteins and the role of cytokines in regulation of HIV expression. Our
      understanding of the precise mechanisms whereby HIV causes a loss of CD4+ T cells
      remains incomplete. The direct infection and cell killing of CD4+ T cells is
      important and is supported by recent evidence demonstrating a high viral burden
      in these cells in the lymphoid tissue of patients. Over the last 1 to 2 years,
      there has been new evidence for indirect mechanisms of CD4+ T-cell depletion
      and/or dysfunction including: autoimmune reactions, perturbations of specific V
      beta T-cell receptor populations, infection of T-cell precursors in bone marrow
      and thymus, immunosuppression and dysregulation by viral proteins, possible super
      antigen effects, and antigen-induced apoptosis or programmed cell death. New
      information has come forth in our understanding of B-cell abnormalities in HIV
      pathogenesis, including the putative role of IL-6 in B-cell activation and the
      identification of EBV in B-cell lymphomas in the CNS of patients with AIDS. It is
      expected that these and future discoveries concerning immunopathogenesis of HIV
      infection will help steer the therapeutic effort. Major strides continue to be
      made in the therapeutic arena for HIV infection and its complications.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8140959
TI  - Evolving concepts in the pathogenesis and management of asthma.

PMID- 8140960
TI  - The techniques of molecular biology and their application to the
      cardiomyopathies.

PMID- 8140961
TI  - Medical management of coronary artery disease after angioplasty and thrombolytic
      therapy.

PMID- 8140962
TI  - Coronary artery disease in women: diagnosis and prevention.

PMID- 8140963
TI  - Approach to treatment of the patient with heart failure in 1994.

PMID- 8140964
TI  - Alcoholic liver disease: new concepts of pathogenesis and treatment.

PMID- 8140965
TI  - Obstructive sleep apnea.

PMID- 8140966
TI  - Medical management of hyperlipidemic states.

PMID- 8140967
TI  - Hypertension and diabetic vascular complications.

PMID- 8140968
TI  - Evaluation of the hypothalamic-pituitary-adrenal axis: importance in steroid
      therapy, AIDS, and other stress syndromes.

PMID- 8140969
TI  - Genetic mechanisms of solid tumor oncogenesis.
AB  - The study of the genetic alterations of tumor suppressor genes and protooncogenes
      in solid tumors has greatly increased our understanding of cancer biology. These
      findings have extended epidemiologic associations of carcinogens with certain
      tumors. Further analysis of patterns of genetic changes may implicate
      carcinogenic substances in cases where epidemiology has not been able to do so.
      Identification of germline mutations in p53, APC, and NF1 has provided improved
      diagnosis and presymptomatic screening in cancer kindreds. The identification of
      additional alterations in tumor suppressor genes may further improve the ability
      to predict inherent cancer risk. Screening strategies based on detection of
      genetic abnormalities of preinvasive cancerous lesions, such as mutant ras in
      colonic polyps, may improve early diagnosis. Finally, strategies to replace lost
      tumor suppressor function may provide a future therapeutic modality.

PMID- 8140970
TI  - The current management of gastric cancer.
AB  - Gastric cancer remains a serious public health problem in many regions of the
      world. The failure to improve results following surgical resection and adjuvant
      therapy in the West has led to an increased interest in the Japanese approach to
      the management of gastric cancer. The detailed staging system proposed in Japan
      permits a more rational, type-oriented therapy and a better anatomic planning of
      the operation. However, experience in the West indicates that radical operations
      have not yielded the excellent results reported from Japan, neither in terms of
      morbidity and mortality nor in 5-year survival. It is possible that early
      diagnosis, the variable virulence of the diverse types of tumors, and other not
      well-defined factors have importance in determining the striking differences in
      results reported from Japan and from the Western countries. The surgeon must
      weigh the potential increased morbidity and mortality of radical surgery vs. its
      potential benefits in terms of locoregional control of the disease.
      Intraoperative radiotherapy may permit better local and regional control of
      disease; it must be further evaluated. Endoscopic ablation of early gastric
      cancer may be increasingly utilized in the future through improved selection of
      patients. DNA ploidy studies may reveal patients at variable risk, so that more
      rational individualized therapy can be implemented. Increased detection of early
      cancers through more aggressive endoscopic examination of populations at high
      risk, and improved systemic therapy, are the most immediate desirable goals in
      the management of this very serious, highly lethal disease.

PMID- 8140971
TI  - Breast reconstruction in the postsilicone era.

PMID- 8140972
TI  - Current management of diverticulitis.

PMID- 8140973
TI  - Endoscopic management of esophageal varices.

PMID- 8140974
TI  - The incidence and management of complications of laparoscopic cholecystectomy.

PMID- 8140976
TI  - The management of thoracoabdominal aneurysms.

PMID- 8140975
TI  - Diagnosis and management of gastric emptying disorders.
AB  - In summary, although gastric emptying disorders are relatively uncommon, they are
      potentially devastating conditions resulting from pathophysiologic motor
      disturbances. Rapid gastric emptying of liquids is the hallmark of the dumping
      syndrome and occurs after operations, including vagotomy. Vagal denervation
      abolishes receptive relaxation and accommodation in the proximal stomach (the
      storage site for ingested liquids) resulting in increased intragastric pressure
      which forces liquids through an ablated or bypassed pylorus. Dumping symptoms may
      occur in up to 50% of postgastrectomy patients, but most patients are treated
      satisfactorily by dietary manipulation or, in the rare incapacitated patient, by
      the long-acting somatostatin analogue octreotide. Reconstructive gastric surgery
      may rarely be indicated to slow gastric emptying and alleviate the dumping
      syndrome. Reoperative procedures include pyloric reconstruction after
      pyloroplasty, small intestinal pouches, interposed isoperistaltic and
      antiperistaltic jejunal segments, and a Roux-en-Y gastrojejunostomy. Interposed
      jejunal loops and the Roux-en-Y gastrojejunostomy provide the most satisfactory
      results. Delayed gastric emptying may occur in the acute postoperative period or
      be a late complication of gastric surgery. Loss of vagal input to the gastric
      antrum and resection of the antrum with vagotomy may produce an atonic stomach or
      atonic gastric remnant, respectively, which fails to grind and propel solids into
      the small intestine. Scintigraphic imaging of both the liquid and solid
      components of the meal is a valuable diagnostic adjunct. Gastric ileus occurring
      in the early postoperative period generally resolves within 6 weeks of operation,
      and the temptation to reoperate on a nonobstructed stomach should be avoided.
      Pharmacologic therapy of chronic gastric stasis with the benzamide prokinetic
      agents (metoclopramide, cisapride, renzapride), domperidone, and the motilin
      agonist erythromycin, may be effective initially, but long-term results are still
      undefined, and postvagotomy and postgastrectomy patients have not been studied
      adequately. Persistent postoperative gastric atony and the Roux stasis syndrome
      should be managed surgically by near-total gastrectomy which should result in
      symptomatic improvement in two thirds of patients.

PMID- 8140977
TI  - Current status of intestinal transplantation.

PMID- 8140978
TI  - Esophagectomy for benign disease: use of the colon.

PMID- 8140979
TI  - Prophylactic antibiotics and their role in the prevention of surgical wound
      infection.
AB  - Prophylactic antibiotics are indicated in all clean-contaminated and many clean
      procedures, especially in view of the low complication rates seen with
      cephalosporin prophylaxis. They are best administered immediately before
      operation in a manner that insures a tissue level at the time of incision and
      they should target pathogens commonly associated with the specific operation
      undertaken. Therapeutic tissue concentrations should be maintained throughout the
      period of potential bacterial contamination but not beyond 24 hours after
      surgery. Linton has been proved corrected in predicting the contribution of
      preventive (prophylactic) antibiotics to surgery. They are a useful tool in the
      surgeon's effort to minimize the occurrence of postoperative infection. However,
      these agents must be used with, and cannot replace, meticulous and aseptic
      surgical technique. Current research providing information concerning the basic
      cellular and molecular bases of host defense against bacterial primary lodgment
      and invasion provide strong evidence that the surgical patient of the future will
      benefit by an extended ability to normalize natural host defenses rendering those
      few bacteria that gain access to the wound incapable of producing infection. At
      that time preventive (prophylactic) antibiotics will become less important in the
      control of postoperative infection.

PMID- 8140980
TI  - Distal vein bypass: the modern method of limb salvage.

PMID- 8140981
TI  - Management of penetrating trauma to the neck.

PMID- 8140982
TI  - Pulmonary changes due to radiation therapy vs changes due to recurrent neoplasia
      or infection: use of radiation therapy portal chest radiographs for comparison.

PMID- 8140983
TI  - Malignant pleural mesothelioma and rounded atelectasis.

PMID- 8140984
TI  - Esophageal perforation: role of esophagography and CT.

PMID- 8140985
TI  - Biopsy of portal vein thrombus.

PMID- 8140986
TI  - Testicular microlithiasis.

PMID- 8140987
TI  - Krukenberg's tumor diagnosed on the basis of findings on endoscopic sonograms.

PMID- 8140988
TI  - The challenge of managed care and managed competition.
AB  - Payment for health care in the United States changed rapidly during the 1980s,
      with the changes often identified by three-letter acronyms such as HMO, PPO, DRG,
      and RVS (health maintenance organization, preferred provider organization,
      diagnosis-related group, and relative value system). Changes are likely to be
      even more rapid and fundamental in the next few years. "Managed care" and
      "managed competition" are the principal terms being used to describe these
      pending changes. In this paper, we briefly present the problems that have led to
      changes, the changes that have occurred, the changes likely in the future, the
      implications of these changes for radiologists, and how radiologists can respond
      most effectively. We concentrate on the implications of changes for radiologists
      and on how radiologists can respond effectively.

PMID- 8140989
TI  - Follow the money to see where health care reform is leading.

PMID- 8140990
TI  - Expediting the turnaround of radiology reports: use of total quality management
      to facilitate radiologists' report signing.
AB  - OBJECTIVE: The purpose of this study was to determine whether total quality
      management techniques could be used to speed radiologists' performance on the
      task of signing reports. SUBJECTS AND METHODS: Total quality management
      represents a group of tools that can be used to improve the functioning of
      complex processes in the workplace. The steps involved in our total quality
      management project were as follows: (1) commit to improving radiologists'
      performance, (2) commission an interdisciplinary study team, (3) propose
      hypotheses for the causes of signing delays, (4) identify the key issues
      constraining performance (Pareto analysis), (5) intervene to correct systematic
      problems in a test system, (6) evaluate the results of intervention on
      radiologists' report signing performance, and (7) hold the gains achieved by the
      intervention. An interdisciplinary study team identified five key obstacles to
      prompt signing of reports: (1) radiologists' absence from the department when
      reports were available for signing (e.g., nights and weekends), (2) dysfunctional
      hand-off between transcriptionist and radiologist, (3) requirement that a fellow
      or resident sign before a staff radiologist, (4) lack of a system for signing by
      proxy (if primary radiologist is away), (5) perceived lack of impact of signed
      report on clinical decision making. RESULTS: Interventions included (1) providing
      home computer terminals, (2) implementing a buddy system for proxy signing, (3)
      eliminating the requirement for a signature from a fellow or resident, (4)
      teaming groups of radiologists with specific transcriptionists, and (5)
      streamlining transcription service. When these enhancements were used in a test
      system, the mean time required to sign reports decreased 59% from 26.0 +/- 8.4 hr
      (mean +/- standard error) in the baseline period to 10.6 +/- 2.9 hr (in the
      enhanced period, p = .05). CONCLUSION: We conclude that total quality management
      methods can accelerate radiologists' signing of reports.

PMID- 8140991
TI  - Lessons of a Figley fellow, or how I learned to stop worrying and love the
      publication game.

PMID- 8140992
TI  - CT of the lung in patients with pulmonary emphysema: diagnosis, quantification,
      and correlation with pathologic and physiologic findings.
AB  - Pulmonary emphysema is a pathologic diagnosis. However, the diagnosis can be made
      with relative certainty on the basis of clinical and radiologic criteria. The
      clinical diagnosis of emphysema can be difficult because correlations between
      results of lung function tests and the extent of emphysema are poor.
      Additionally, features of other obstructive lung diseases may overlap. From the
      clinician's standpoint, the main value of differentiating between emphysema and
      other obstructive diseases of the airways (e.g., asthma and chronic bronchitis)
      is to (1) establish a prognosis and (2) guide the use of corticosteroid therapy
      by defining the degree of reversibility that can be expected in patients with
      limitation in air flow.

PMID- 8140993
TI  - Metastatic pulmonary calcification in patients with hypercalcemia: findings on
      chest radiographs and CT scans.
AB  - OBJECTIVE: The objective of this study was to characterize the findings on chest
      radiographs and CT scans in patients with metastatic pulmonary calcification due
      to hypercalcemia. MATERIALS AND METHODS: The chest radiographs and CT scans of
      seven patients with biopsy-proved metastatic pulmonary calcification were
      reviewed by two observers. Metastatic calcification was due to chronic renal
      failure (n = 4), T-cell leukemia (n = 1), multiple endocrine neoplasia type I
      syndrome (n = 1), and idiopathic hypercalcemia (n = 1). RESULTS: Numerous nodular
      opacities measuring 3-10 mm in diameter were seen on the chest radiographs in
      five cases, and patchy areas of parenchymal opacification were seen in two cases.
      Calcification of the nodules was evident in two cases. On CT scans, pulmonary
      nodules were present in all seven cases. These nodules were predominant in the
      upper lung zone in three cases, were diffuse in three cases, and were predominant
      in the lower lung zone in one case. Calcification of the nodules was evident on
      the CT scans in four of the seven cases, and calcification of vessels in the
      chest wall was evident in six of seven cases. Other findings on CT scans included
      diffuse areas of ground-glass attenuation (n = 3) and patchy consolidation (n =
      2). CONCLUSION: Numerous small nodules are the most common finding on the chest
      radiographs of patients with metastatic pulmonary calcification. The calcific
      nature of the nodules is seldom obvious, however. Pulmonary nodules are also the
      most common finding on CT scans, where the calcific nature of the nodules is more
      readily apparent. Additionally, calcification is often seen in the vessels of the
      chest wall on CT scans. The combination of calcified nodules and calcified
      vessels in the chest wall on CT scans may be characteristic.

PMID- 8140994
TI  - Proliferative and constrictive bronchiolitis: classification and radiologic
      features.
AB  - The small airways of the lung consist of the terminal bronchioles, respiratory
      bronchioles, and alveolar ducts. A recently introduced pathologic classification
      system divides bronchiolitis into proliferative and constrictive types. The
      histologic classification of small-airways disease into proliferative and
      constrictive bronchiolitis frequently correlates with the radiographic
      appearances. Proliferative bronchiolitis is characterized by air-space
      opacification, whereas constrictive bronchiolitis tends to be associated with
      lobular areas of decreased attenuation and airway dilatation. The purpose of this
      essay is to illustrate the radiographic and CT features of these two varieties of
      bronchiolitis.

PMID- 8140995
TI  - MR features of arrhythmogenic right ventricular dysplasia.
AB  - Arrhythmogenic right ventricular dysplasia is defined as a primary disorder of
      the right ventricle characterized by partial or total replacement of muscle by
      adipose or fibrous tissue. Its diagnosis currently rests on techniques that
      accurately identify specific anatomic and functional abnormalities of the right
      ventricle. To date, none of these methods (except for autopsy) are specific for
      right ventricular dysplasia although angiography of the right ventricle is
      considered to be the current gold standard. MR imaging shows promise in
      clarifying the diagnosis of right ventricular dysplasia. This pictorial essay
      describes our current technique for examining the right ventricular myocardium in
      patients thought to have this disease and illustrates the spectrum of
      abnormalities encountered in these patients.

PMID- 8140996
TI  - Intimointimal intussusception in aortic dissection: CT diagnosis.

PMID- 8140997
TI  - Breast biopsy: a comparative study of stereotaxically guided core and excisional
      techniques.
AB  - OBJECTIVE: The major objectives of this prospective study were to compare
      pathologic findings from stereotaxic core and excisional biopsies performed on
      patients with impalpable breast lesions and to compare the initial mammographic
      impression with the final histologic diagnosis. SUBJECTS AND METHODS: All
      patients referred for preoperative localization of impalpable breast lesions
      between October 29, 1991, and January 15, 1993, were eligible for the study. If
      the patient and the lesion, on the basis of mammography, were considered suitable
      for core biopsy, the patient was asked to participate. Four hundred forty-five
      excisional biopsies were performed. One hundred sixty lesions were evaluated by
      core biopsy; for 104 of these lesions, five or more core samples were removed.
      Core biopsies were done with 14-gauge biopsy needles and were followed by a
      localization procedure. The pathologic features of core and excisional specimens
      were compared. RESULTS: Biopsy results were compared for 93 (58%) benign and 67
      (42%) malignant lesions. Of 104 lesions evaluated with at least five core
      specimens, 56 (54%) were benign and 48 (46%) were malignant. Results of core
      biopsy corresponded to those of excisional biopsy for 96% of benign lesions, 83%
      of malignant lesions, and 90% overall; sensitivity of core biopsy for malignant
      lesions was 85%. Of 56 lesions for which fewer than five core specimens were
      obtained, 37 (66%) were benign and 19 (34%) were malignant. Results of core
      biopsy corresponded to those of excisional biopsy for 81% of benign lesions, 79%
      of malignant lesions, and 80% overall; sensitivity of core biopsy for malignant
      lesions was 84%. Specificity of core biopsy for the entire series of benign
      lesions was 100%. CONCLUSION: For mammographic lesions that are believed to be
      not malignant or not very likely malignant, stereotaxic core biopsy decreases the
      need for excisional biopsy.

PMID- 8140998
TI  - Ductal abnormalities detected with galactography: frequency of adequate
      excisional biopsy.
AB  - OBJECTIVE: Galactography (ductography) is a contrast examination of the mammary
      ducts performed to identify and localize intraductal growths that may be the
      cause of spontaneous discharge from the nipple. The objective of this study was
      to correlate the radiologic-pathologic findings in patients with abnormal
      findings on galactograms in order to determine how often the biopsy specimens
      included the lesions seen at galactography. MATERIALS AND METHODS: We
      retrospectively studied all galactograms with abnormal findings obtained in women
      who subsequently had biopsy at our institution between 1981 and 1991.
      Galactograms and tissue specimens from 29 women who had 30 biopsies were
      included. The standard technique was used to perform galactography. Biopsies were
      performed by using standard surgical technique for duct excision. The
      histopathologic findings were retrospectively reviewed by a pathologist to
      determine whether the biopsy specimens included the lesions seen at
      galactography. RESULTS: In six (20%) of the 30 biopsies, the lesion shown by
      galactography was not seen on histopathologic review. In the other 80%, the
      lesion was successfully identified on histopathologic examination. CONCLUSION:
      Our finding that the abnormality shown by galactography was not completely
      excised in one in five cases indicates that greater cooperation between the
      surgeon, radiologist, and pathologist is essential to ensure that all lesions are
      properly removed.

PMID- 8140999
TI  - Hydatid cyst of the breast: mammographic findings.

PMID- 8141000
TI  - Treatment of hepatocellular carcinoma with percutaneous ethanol injection:
      evaluation with contrast-enhanced MR imaging.
AB  - OBJECTIVE: The aim of this study was to investigate the usefulness of unenhanced
      and enhanced MR imaging in evaluating the response of hepatocellular carcinoma to
      percutaneous injection of ethanol. SUBJECTS AND METHODS: Thirty-one patients with
      40 hepatocellular carcinomas less than 5 cm in diameter were examined with MR
      imaging before and after percutaneous injection of ethanol. Unenhanced T1- and T2
      weighted and contrast-enhanced T1-weighted spin-echo images were obtained. CT and
      percutaneous biopsy were performed 1 month after the final injection of ethanol
      and repeated at 6-month intervals to establish the outcome of treatment: complete
      tumor necrosis was shown in 36 lesions and incomplete tumor necrosis was seen in
      four lesions. RESULTS: Of the 36 proved necrotic lesions, 31 showed homogeneously
      low signal intensity on T2-weighted MR images obtained after treatment, owing to
      coagulative necrosis of the tumor. In the remaining five necrotic lesions,
      hypointense and hyperintense areas coexisted; the hyperintense areas were caused
      by liquefactive necrotic material in two cases and by chronic inflammatory tissue
      along the boundary of the necrotic area in three cases. None of the 36 necrotic
      lesions showed contrast enhancement on T1-weighted images obtained after IV
      injection of gadopentetate dimeglumine. In the four lesions with incomplete
      necrosis, the viable portion of the tumor was identified as a hyperintense area
      on T2-weighted images and as an enhancing area on contrast-enhanced T1-weighted
      images. No correlation was found between lesion features on unenhanced T1
      weighted images and outcome of therapy. CONCLUSION: Contrast-enhanced T1-weighted
      MR images allow a reliable evaluation of the effectiveness of treatment and are
      more accurate than unenhanced MR studies. Contrast-enhanced MR imaging may be
      considered a valuable alternative to contrast-enhanced CT in the follow-up of
      hepatocellular carcinomas treated with percutaneous injection of ethanol.

PMID- 8141001
TI  - Abnormalities of Doppler waveform of the hepatic veins in patients with chronic
      liver disease: correlation with histologic findings.
AB  - OBJECTIVE: Changes in the Doppler waveform of the hepatic veins are associated
      with chronic liver disease, particularly cirrhosis. We correlated abnormalities
      in Doppler waveforms of hepatic veins with histologic findings in the liver to
      determine the accuracy of Doppler imaging in the detection of cirrhosis. SUBJECTS
      AND METHODS: Fifty-two patients with chronic hepatitis C were examined
      prospectively and blindly by two sonographers. In the same session, a liver
      biopsy specimen was obtained from each patient and submitted to three independent
      pathologists for conventional interpretation and for grading of severity
      according to a predetermined scoring system. Duplex sonography of the hepatic
      veins was also performed in 50 control subjects. RESULTS: Abnormal hepatic vein
      waveforms were detected in 12 of 16 patients with cirrhosis and in eight of 36
      patients without cirrhosis. However, histologic examination of the biopsy
      specimens showed that only two of the eight patients without cirrhosis had no
      significant abnormalities, other than mild portal inflammation. Abnormal
      waveforms were seen in no control subjects. We found a correlation between
      fibrosis and steatosis and abnormalities in the Doppler waveform of the hepatic
      veins (r = .50, p < .001). Portal inflammation, intralobular degeneration, and
      necrosis did not correlate with an abnormal waveform. CONCLUSION: Duplex
      sonography of the hepatic veins may be useful for studying liver disease
      associated with fibrosis and steatosis. In patients with well-compensated liver
      disease, flattening of the Doppler waveform of the hepatic vein suggests the
      presence of cirrhosis.

PMID- 8141002
TI  - Medicine in American art. The doctor.

PMID- 8141003
TI  - Hepatic vein flow reversal at duplex sonography: a sign of transjugular
      intrahepatic portosystemic shunt dysfunction.

PMID- 8141004
TI  - Large-bowel obstruction resulting from traumatic diaphragmatic hernia: imaging
      findings in four cases.
AB  - OBJECTIVE: Large-bowel obstruction is most often due to primary carcinoma,
      diverticulitis, or volvulus. In populations of patients in which trauma is
      prevalent, however, an additional important consideration is traumatic
      diaphragmatic hernia. We describe the findings on plain radiographs and single
      contrast enema in four adults who had vague complaints of abdominal pain days to
      months after an abdominal stab injury and large-bowel obstruction resulting from
      herniation of colon or omentum through the left hemidiaphragm. MATERIALS AND
      METHODS: We retrospectively analyzed plain radiographs of the chest and abdomen
      that were obtained before confirmation of colonic obstruction by single-contrast
      enema, surgery, or both in four men. Herniation of colon or omentum through the
      left hemidiaphragm was confirmed at surgery in all four cases. RESULTS:
      Posteroanterior and lateral radiographs of the chest obtained as part of the
      initial evaluation showed, in all four cases, abnormalities of the left
      hemidiaphragmatic contour. These included elevation of the hemidiaphragm in one
      case, loss of definition of a portion of the hemidiaphragm due to adjacent
      confluent opacity in two cases, pleural effusion in two cases, and small cystic
      lucencies above the diaphragmatic contour in one case. Abdominal radiographs
      obtained at the same time as the initial chest radiograph showed normal findings
      in two cases and mild dilatation of gas-filled colon in the upper part of the
      abdomen in two cases. In three of the four patients, progressive dilatation of
      the colon to the level of the splenic flexure was seen on serial abdominal
      radiographs. Large-bowel obstruction was confirmed by single-contrast enema in
      three cases and surgery in four cases. Minimal dilatation of the large bowel in
      the fourth patient resolved the day after admission; however, progression to
      complete obstruction was shown by single-contrast enema the following day.
      CONCLUSION: Delayed herniation through a trauma-induced defect in the left
      hemidiaphragm can be an unsuspected cause of large-bowel obstruction.
      Abnormalities of the left hemidiaphragmatic contour on plain radiographs of the
      chest should suggest the diagnosis in patients who have abdominal pain, colonic
      dilatation, and a history of abdominal injury.

PMID- 8141005
TI  - Early radiology of pulmonary tuberculosis.

PMID- 8141006
TI  - Screening patients for renal artery stenosis: value of three-dimensional time-of
      flight MR angiography.
AB  - OBJECTIVE: The purpose of this study was to determine the value of three
      dimensional time-of-flight MR angiography in screening patients for the presence
      of renal artery stenoses. SUBJECTS AND METHODS: Fifty-three patients who were
      thought to have renovascular hypertension on clinical grounds were prospectively
      examined with three-dimensional time-of-flight MR angiography. IV digital
      subtraction angiograms and duplex sonograms were available for all patients. For
      21 patients in whom IV angiograms were of high quality and showed the renal
      arteries to be normal, as confirmed with duplex sonograms, intraarterial digital
      subtraction angiograms were not obtained for MR correlation. In the other 32
      patients, intraarterial angiograms of the abdominal aorta were obtained. MR
      angiograms were interpreted independently by two radiologists who were unaware of
      the findings on angiography and duplex sonography. Our preliminary clinical
      experience suggested that a signal loss in the renal arteries on maximum
      intensity-projection MR angiograms indicated a potential stenosis and that the
      degree of stenosis could not be measured accurately with MR angiography. The
      search for stenoses was focused on the proximal and middle parts of the vessel,
      as far as 3 cm from the origin of the vessel. We used intraarterial angiography
      to measure and grade renal artery stenoses. On intraarterial angiograms, stenoses
      that involved more than 50% of the vessel's section were considered significant
      (n = 24) and stenoses that involved 50% or less of the section were considered
      insignificant (n = 7). These 31 stenoses were found in 26 of the 32 patients who
      had intraarterial digital subtraction angiography. RESULTS: All 24 significant
      stenoses appeared as a cutoff of signal intensity on MR angiograms. Results were
      false-positive in 20 cases: in eight cases, arteries were of small diameter; in
      seven cases, the stenoses were insignificant; in two cases, the acquisition
      volume was incorrectly positioned; in two cases, there was a sharp angle in the
      proximal part of the renal artery; and in one case, no explanation was found. MR
      angiography had a sensitivity of 100% for detecting stenoses in the proximal 3 cm
      of the renal artery; stenoses more than 3 cm from the origin of the arteries
      could not be detected reliably. CONCLUSION: Our results suggest that three
      dimensional time-of-flight MR angiography is a simple method for detecting
      stenoses of the proximal portion of the main renal arteries. However, more work
      is needed before widespread clinical use of such a technique is feasible.

PMID- 8141007
TI  - Renal artery angioplasty for renovascular hypertension and preservation of renal
      function: long-term angiographic and clinical follow-up.
AB  - OBJECTIVE: Percutaneous transluminal angioplasty of stenoses of the renal artery
      can be used to treat hypertension and renal insufficiency. Although many studies
      have been published on the short-term results of this procedure, few long-term
      studies are available. SUBJECTS AND METHODS: One hundred ninety-five patients
      (123 men and 72 women 19-79 years old; mean age, 56 years) with stenosis of the
      renal artery and hypertension underwent renal percutaneous transluminal
      angioplasty at our institution. The stenosis was unilateral in 66% of patients,
      bilateral in 26%, and in a solitary functioning kidney in 8%. Renal insufficiency
      was present in 31% of patients. After renal percutaneous transluminal
      angioplasty, long-term clinical and angiographic follow-up was evaluated by life
      table analysis. RESULTS: In patients with fibromuscular disease, blood pressure
      returned to normal in 57%, improved in 21%, and was unchanged in 21%. In patients
      with atherosclerotic stenosis, blood pressure returned to normal in 12%, improved
      in 51%, and was unchanged in 37%. After percutaneous transluminal angioplasty,
      renal function improved in 48% of patients with renal insufficiency due to
      bilateral stenosis or stenosis in the single functioning kidney, whereas none of
      the patients with unilateral stenosis of renal artery and renal insufficiency had
      any notable improvement. Long-term follow-up showed a high rate (82%) of patency
      of revascularized arteries and a low rate (21%) of hypertension recurrence at 5
      years. CONCLUSION: Renal percutaneous transluminal angioplasty is useful for
      treating hypertension and for reestablishing renal function. Its effects on blood
      pressure and renal function are long-lasting in the large majority of patients.

PMID- 8141008
TI  - Intraoperative color Doppler sonography during renal artery revascularization.
AB  - Intraoperative color Doppler sonography is emerging as a useful procedure for
      evaluating renal arteries during transaortic renal endarterectomy or bypass
      grafting. Technical difficulties encountered during surgical renal
      revascularization, such as intimal defects or flaps, partial or complete
      thrombosis, and anastomotic stenosis of the renal artery, can be difficult to
      defect and evaluate. Intraoperative color Doppler sonography allows evaluation at
      a time when the problem is often correctable. We have been performing
      intraoperative sonographic studies of the renal artery for several years and have
      studied 151 vessels. In this pictorial essay, we present some of our observations
      on these cases.

PMID- 8141009
TI  - MR imaging and sonography of early prostatic cancer: pathologic and imaging
      features that influence identification and diagnosis.
AB  - OBJECTIVE: The purpose of this study was to correlate findings at MR imaging and
      transrectal sonography with histopathologic findings after surgery in patients
      with prostatic cancer, to identify the pathologic characteristics of prostatic
      cancer that improved detection with MR imaging and transrectal sonography, and to
      identify the imaging characteristics that correlated with detection of true
      cancers. MATERIALS AND METHODS: Data from MR imaging in 320 patients and from
      transrectal sonography in 343 patients who were enrolled in the Radiological
      Diagnostic Oncology Group multiinstitutional study of imaging in prostatic cancer
      were correlated with results of radical prostatectomy. Only cancers 5 mm or
      greater in at least one dimension were evaluated pathologically. The locations of
      lesions and the linear dimensions and volumes of individual lesions and the
      prostate gland were evaluated pathologically and with imaging studies. The
      appearance of lesion margins on images and the degree of differentiation of
      lesions seen on pathologic examination were also studied. Univariate and
      multivariate analysis were performed to determine the pathologic findings
      associated with imaging detection and the imaging characteristics associated with
      prostatic cancer. RESULTS: MR imaging and transrectal sonography showed 62% and
      64% of cancers, respectively, each with a positive predictive value of 68%.
      Cancers that were larger, moderately or poorly differentiated, or located in the
      posterior half of the outer gland were easier to detect (p < .0001). The overall
      size of the prostate did not effect lesion detection. However, abnormalities
      identified in the posterior half of the outer gland were more likely to be
      cancers. On transrectal sonograms, larger abnormalities also were more likely to
      be malignant tumors. The sharpness of the margins of the imaged abnormalities did
      not predict pathologic status. CONCLUSION: Detection of prostatic cancer with MR
      imaging or transrectal sonography is affected by cancer size, differentiation,
      and location; the odds of an imaged lesion's being malignant are related to
      location and, for transrectal sonography, size. Knowledge of anatomic/pathologic
      features that enhance lesion detection may help when using imaging tests to
      detect prostatic carcinoma. That certain imaging characteristics of lesions are
      associated with true cancers may assist in the interpretation of MR images and
      transrectal sonograms of the prostate.

PMID- 8141010
TI  - Angiographic evaluation and therapy of ureteroarterial fistulas.
AB  - OBJECTIVE: Fistulas between the iliac artery and the ureter are extremely
      uncommon, life-threatening conditions usually seen in patients who have had
      pelvic irradiation or have indwelling ureteral stents. We describe our experience
      in the angiographic evaluation and therapy of these fistulas. MATERIALS AND
      METHODS: We retrospectively reviewed medical records for diagnoses of
      ureteroarterial fistulas. Patients' records were evaluated for potentially
      associated etiologic factors, clinical features and course, radiographic
      evaluation and findings, and therapy. RESULTS: Our review showed that four
      patients treated at our institution (all since 1990) had ureteroarterial
      fistulas. All four patients had indwelling ureteral stents and had had
      irradiation for pelvic cancer. Three had spontaneous brisk hemorrhage in the
      urinary tract. The fourth had hemorrhage after balloon dilatation of a ureteral
      stricture. Initial diagnosis was based on findings on iliac arteriography in
      three patients and on findings on retrograde ureterography in one. Angiographic
      techniques required to visualize the fistulas included selective arterial
      catheterization, use of multiple projections, and provocative maneuvers.
      Treatment of the ureteroarterial fistulas involved surgery in one case, isolated
      embolotherapy in one case, and a combination of embolotherapy and surgery in two
      cases. CONCLUSION: Specific angiographic maneuvers are often required to identify
      ureteroarterial fistulas. Transcatheter embolotherapy (with or without surgical
      bypass) is an effective form of treatment for this rare abnormality.

PMID- 8141011
TI  - New method for simultaneous placement of antegrade ureteral stent and nephrostomy
      tube.

PMID- 8141012
TI  - Radiologic diagnosis of traumatic occipitovertebral dissociation: 1. Normal
      occipitovertebral relationships on lateral radiographs of supine subjects.
AB  - OBJECTIVE: The objective of this study was to establish a reliable method of
      determining the normal occipitovertebral relationship seen on lateral radiographs
      of the cervical spine in supine subjects in order to recognize alterations of
      normal that characterize occipitovertebral dissociation. MATERIALS AND METHODS:
      We define the rostral extension of the posterior cortex of the axis body as the
      posterior axial line, the distance between the basion (tip of the clivus) and the
      posterior axial line as the basion-axial interval, and the distance between the
      basion and the rostral tip of the dens as the basion-dental interval. The basion
      axial interval was measured on horizontal-beam lateral radiographs of the
      cervical spine obtained at a 40-in. (1-m) target-film distance in 400 adults who
      had no occipitovertebral abnormalities. The basion-dental interval was measured
      in 374 (94%) of the same cohort of adults in whom the superior cortex of the dens
      could be identified. All radiographs were obtained with the subjects supine. The
      excursion of the basion referable to the posterior axial line was determined on
      lateral flexion and extension radiographs of 25 of the same cohort of adults. The
      basion-axial interval only was measured on radiographs of 50 children 2-13 years
      old who had no occipitovertebral abnormalities. RESULTS: In 392 (98%) of the 400
      adults, the basion-axial interval did not exceed 12 mm. In eight adults (2%), the
      basion was situated 1-4 mm posterior to the posterior axial line. The excursion
      of the basion in flexion and extension ranged from 0 to 10 mm, but did not exceed
      the 12-mm limit of normal. The basion translated posterior to the posterior axial
      line in six (24%) of the 25 adults in whom excursion was measured. Of the 400
      adults, the basion-dental interval ranged from 2 to 15 mm (mean, 7.5 +/- 4.3 mm
      [2 SD]); the 95% accuracy range was 11.8 mm. In all 50 children (100%), the
      basion was within the normal basion-axial interval of 12 mm, and in no instance
      was the basion posterior to the posterior axial line. CONCLUSION: In adults, the
      occipitovertebral junction can be considered normal when both the basion-axial
      interval and basion-dental interval are 12 mm or less. In children less than 13
      years old, the basion-dental interval is not reliable because of the variable age
      at which complete ossification and fusion of the dens occur. The normal basion
      axial interval in children did not exceed 12 mm. This simple, anatomically based
      method of recognizing normal occipitovertebral relationships facilitates
      identification of occipitovertebral dissociation.

PMID- 8141013
TI  - Radiologic diagnosis of traumatic occipitovertebral dissociation: 2. Comparison
      of three methods of detecting occipitovertebral relationships on lateral
      radiographs of supine subjects.
AB  - OBJECTIVE: The purpose of this study was to describe a method for recognizing
      acute traumatic occipitoatlantal dissociation that uses the basion-axial interval
      and basion-dental interval and to compare the accuracy of this method with the
      accuracies of two other methods: the Powers ratio and the x-line method.
      MATERIALS AND METHODS: Lateral radiographs of the cervical spine of 37 patients
      in whom the diagnosis of occipitoatlantal dissociation had been made on the basis
      of the relationship of the basion to the tip of the dens, the Powers ratio,
      and/or the x-line method were reviewed. Retrospectively, the occipitoatlantal
      junction of each was reassessed by using the the Powers ratio, the x-line, and
      the basion-axial interval-basion-dental interval methods. Independently, the
      neurologic findings at admission and the final neurologic diagnosis at discharge
      were obtained from the hospital records and were compared with the radiologic
      findings to determine the degree of radiologic-clinical correlation. RESULTS:
      Three groups of patients were identified by analyzing the basion-axial and basion
      dental intervals of the occipitovertebral junction and related clinical findings.
      Twenty-three patients (group 1) had frank occipitoatlantal dislocation. Eight
      patients (group 2) had incomplete occipitoatlantal dissociation, which was
      defined as occipitoatlantal subluxation. The remaining six patients (group 3) had
      normal radiologic and clinical findings. Four patterns of occipitovertebral
      dissociation were identified: purely anterior (4/31, 13%), purely distracted
      (6/31, 19%), concomitantly anterior and distracted (20/31, 65%), and purely
      posterior (1/31, 3%). Regardless of the magnitude or direction of
      occipitoatlantal dissociation, the basion-axial interval-basion-dental interval
      method correctly identified the abnormality and the type of each. Positive
      clinical correlation was found in 13 (57%) of the 23 patients in group 1 and in
      100% of the eight and six patients in groups 2 and 3, respectively. Neither the
      Powers ratio nor the x-line method could be applied in 17 (46%) of 37 cases,
      either because the opisthion could not be detected on the radiographs or because
      fusion of the posterior arch of C1 had not occurred. In the remaining 20 patients
      in whom the Powers ratio and the x-line method were applicable, the type of
      occipitoatlantal dissociation was correctly identified by the Powers ratio in 12
      (60%) and by the x-line method in four (20%). Neither the Powers ratio nor the x
      line method was applicable in three (50%) of the six patients in whom analysis by
      the basion-axial interval-basion-dental interval method and clinical findings
      showed no occipitoatlantal abnormality. Normal occipitovertebral anatomy was
      correctly identified by the Powers ratio in the remaining three patients (50%)
      and by the x-line method in two (33%). CONCLUSION: Direct measurement of
      occipitovertebral skeletal relationships altered by occipitoatlantal dissociation
      using the basion-axial and basion-dental intervals provides the most accurate
      radiologic assessment of this injury.

PMID- 8141014
TI  - Digital subtraction in contrast-enhanced MR imaging of the postoperative lumbar
      spine.
AB  - OBJECTIVE: The objective of this study was to evaluate the routine use of digital
      image subtraction as an adjunct to standard MR sequences in patients with failed
      lumbar spine surgery. MATERIALS AND METHODS: Unenhanced and contrast-enhanced T1
      weighted MR images of 112 consecutive patients with failed back surgery were
      reviewed, and corresponding axial images at the level of previous surgery were
      digitally subtracted by using standard software. The technique was successful in
      96 patients and was abandoned in 16 owing to patient motion. Two radiologists
      independently assessed the subtracted images for areas of enhancement not seen on
      T1-weighted images, and suggested a diagnosis based on a combination of the
      findings on standard and subtracted images. This diagnosis was compared with the
      original MR diagnosis, and surgical findings were sought in cases of conflict.
      RESULTS: Enhancement was best seen on the subtracted images in muscle fascial
      planes (100%), anterior epidural fibrosis (55%), spinal canal fat (31%),
      posterior epidural fibrosis (27%), types I and II marrow change (24%), and facet
      joints (17%). Subtraction improved the homogeneity of contrast enhancement,
      thereby improving the visualization of nerve roots lying in scar tissue (16%),
      and better defined the extent of epidural fibrosis, particularly when the
      fibrosis was contiguous with fat. The subtracted image increased diagnostic
      confidence in 25% of cases, but altered final diagnosis in only two patients.
      CONCLUSION: Although digital subtraction revealed areas of enhancement not seen
      on standard spin-echo MR images, it rarely altered final diagnosis and does not
      appear to be useful for routine imaging of patients with failed lumbar spine
      surgery. It might, however, be useful for increasing diagnostic confidence or as
      a problem-solving technique in selected patients.

PMID- 8141015
TI  - Fracture of the spine in patients with ankylosis due to diffuse skeletal
      hyperostosis: clinical and imaging findings.
AB  - OBJECTIVE: Only 12 patients with a fracture through a portion of the spine
      ankylosed by diffuse idiopathic skeletal hyperostosis have been reported. The
      purpose of this study was to determine the types of causative trauma, spinal
      sites at risk for fracture, complications mortality, diagnostic difficulties, and
      abnormalities identified only with special imaging studies in a group of 15
      patients with this complication seen at our institution. MATERIALS AND METHODS:
      The study included 15 patients with diffuse idiopathic skeletal hyperostosis who
      had a spinal fracture through an area of ankylosed spine. The criteria for
      diffuse idiopathic skeletal hyperostosis include flowing calcification or
      ossification along the anterolateral margin of at least four contiguous vertebral
      bodies; preservation of disk height in the involved areas; and absence of bony
      ankylosis of the apophyseal joint and erosion, sclerosis, or bony fusion of the
      sacroiliac joints. All spinal radiographs, tomograms, CT scans, and MR images
      obtained in these patients were reviewed to determine diagnostic difficulties,
      site and level of fracture, displacement of fractures, and extent of anatomic
      injury. The hospital charts of all patients were reviewed for history, physical
      examination, clinical status, treatment, and outcome. RESULTS: Fourteen fractures
      of the cervical spine, one of the thoracic spine, and one of the lumbar spine
      occurred in 15 patients. Five fractures were caused by high-energy trauma and 11
      fractures by low-energy, seemingly trivial injuries. The spinal fracture caused
      complete quadriplegia in seven patients, incomplete quadriplegia in one patient,
      complete paraplegia in two patients, a central cord syndrome in two patients, and
      no neurologic deficit in three patients. In two of three patients in whom
      fracture diagnosis was delayed, paraplegia developed during the delay. Three
      patients died within 1 week and three more died within 6 months after injury. CT
      and conventional tomography enabled diagnosis of posterior element fractures not
      seen on plain radiographs in five patients. All fractures healed, except those in
      the three patients who died within a week of injury. CONCLUSION: Trivial trauma
      was the most common cause of fracture in the spine ankylosed by diffuse
      idiopathic skeletal hyperostosis. The severity of spinal cord injury in our
      patients was greater than in previous reports. We suggest that this may be a
      function of the relatively long segments of ankylosed spine (average, 16
      vertebrae) in our patients providing a long lever arm for any traumatic force to
      act on. Patients with shorter ankylosed segments had less severe cord injuries.
      Delay in diagnosis of a fracture through an area of ankylosed spine associated
      with diffuse idiopathic skeletal hyperostosis was common if no neurologic deficit
      was present, and led to permanent paraplegia in two of three patients. CT and MR
      studies were useful in determining the anatomic abnormalities present, but were
      performed only in a limited number of patients.

PMID- 8141016
TI  - Meniscal tears missed on MR imaging: relationship to meniscal tear patterns and
      anterior cruciate ligament tears.
AB  - OBJECTIVE: MR imaging of the knee is a valuable technique for diagnosing meniscal
      tears, but some tears found at arthroscopy are not shown on MR imaging. The
      purpose of this study was to determine whether or not tears were more frequently
      missed in the presence of an anterior cruciate ligament tear or when tears had
      certain locations or configurations. MATERIALS AND METHODS: We reviewed the
      original MR reports and surgical records of 400 patients who had both an MR
      examination and arthroscopy of the knee. Using chi 2 analysis, we examined how
      the sensitivity for detecting meniscal tears varied with the presence of a tear
      of the anterior cruciate ligament, with the location of the tear within the
      meniscus, and among six configurations of meniscal tears. We also studied whether
      sensitivity decreased with an increasing delay between MR examination and
      arthroscopy. RESULTS: In the presence of a tear of the anterior cruciate
      ligament, the sensitivity decreased from 0.97 to 0.88 (p = .016) for medial
      meniscal tears and from 0.94 to 0.69 (p = .0005) for lateral tears. The overall
      sensitivity for lateral meniscal tears was significantly less for posterior (p =
      .001) and peripheral (p = .005) tears than for other tear locations or
      configurations. The sensitivities did not significantly differ between tear
      locations and configurations in the medial meniscus or with an increasing delay
      until arthroscopy. Patients with a torn anterior cruciate ligament were more
      likely to have peripheral tears of the medial meniscus (p = .00004) and posterior
      (p = .0004) and peripheral (p = .04) tears of the lateral meniscus. CONCLUSION:
      Because of their location and configuration, meniscal tears associated with an
      anterior cruciate ligament injury are more difficult to detect on MR images than
      are tears in knees with an intact ligament. If a tear of the anterior cruciate
      ligament is detected, special attention should be given to the subtle peripheral
      tears that may be present in either meniscus, but most commonly in the posterior
      horn of the lateral meniscus. These tears are especially difficult to detect on
      MR images.

PMID- 8141017
TI  - Diagnosis of Achilles tendon xanthoma in patients with heterozygous familial
      hypercholesterolemia: MR vs sonography.
AB  - OBJECTIVE: The purpose of this study was twofold: (1) to determine the
      characteristic MR appearance of the xanthomatous tendons of heterozygous familial
      hypercholesterolemia and (2) to determine which of two imaging techniques, high
      frequency linear-array sonography or MR imaging, is better for detection of
      xanthomas. SUBJECTS AND METHODS: Sonography and MR imaging were performed to
      evaluate the Achilles tendons in 10 patients (20 tendons) with heterozygous
      familial hypercholesterolemia. For sonography, 7.5- (nine patients) and 10.0-
      (one patient) MHz transducers were used. T1-weighted, proton density-weighted,
      and T2-weighted MR images were obtained at 0.5 T (four patients) and 1.5 T (six
      patients), including fat-suppressed (six patients) and water-suppressed (one
      patient) T1-weighted images at 1.5 T. Tendon abnormalities detected with both
      techniques were noted, and the results were compared. RESULTS: In all tendons,
      sonograms showed focal hypoechoic lesions compatible with xanthomas. MR images
      did not show focal lesions. Instead, all pulse sequences showed a diffuse
      speckled or reticulated pattern or both on axial images. This speckled or
      reticulated appearance was more obvious on fat-suppressed T1-weighted images and
      much less evident on water-suppressed T1-weighted images. Contrast resolution was
      subjectively better on sonograms than on MR images in all cases. CONCLUSION: The
      speckled or reticulated appearance is a characteristic, if not pathognomonic, MR
      feature of xanthomatous tendons and probably is due to edema or inflammation, not
      intratendinous lipid. However, localized lipid deposits detected on sonograms are
      more readily quantified than are the lesions seen on MR images. Therefore, we
      think sonography, rather than MR imaging as performed in our study, is the
      technique of choice for detecting xanthomas.

PMID- 8141018
TI  - Giant cell tumor of the tendon sheath: MR findings in nine cases.
AB  - OBJECTIVE: The purpose of this study was to determine the MR findings in patients
      with giant cell tumors of the tendon sheath. MATERIALS AND METHODS: MR imaging
      findings in nine surgically proved cases of giant cell tumors of the tendon
      sheath were evaluated on both T1- and T2-weighted images. Of nine lesions, three
      involved the foot, two involved the thumb, two involved the knee, one involved
      the proximal part of the tibia, and one involved the proximal part of the femur.
      RESULTS: All nine lesions were hypointense on T1-weighted images; the signal
      intensity of most of the tumors was approximately equal to that of skeletal
      muscle. On the T2-weighted images, three lesions were hypointense relative to
      skeletal muscle, two lesions were approximately isointense relative to skeletal
      muscle, and two lesions were slightly hyperintense relative to skeletal muscle
      but hypointense relative to fat. The remaining two lesions had a more
      heterogeneous appearance on T2-weighted images. CONCLUSION: On both T1- and T2
      weighted images, giant cell tumor of the tendon sheath has a signal intensity
      similar to that of its pathologic counterpart, pigmented villonodular synovitis.
      The decreased signal intensity on both T1- and T2-weighted images is an uncommon
      appearance of extraarticular soft-tissue masses, in particular when they occur in
      the hands or feet, and this may suggest the diagnosis of giant cell tumor of the
      tendon sheath.

PMID- 8141019
TI  - MR imaging of the spine: recent advances in pulse sequences and special
      techniques.
AB  - A number of new techniques have been developed to enhance MR imaging of the
      spine. Fat-suppression techniques used in conjunction with gadolinium-based
      contrast material improve visualization of enhancing inflammatory and neoplastic
      diseases. Fast spin-echo (FSE) sequences can be used to decrease imaging times,
      to increase resolution, or to improve signal-to-noise ratios on T2-weighted
      images. In general, FSE images provide a better myelographic effect with reduced
      magnetic susceptibility compared with gradient-recalled echo (GRE) techniques.
      With volume GRE sequences, thin contiguous sections can be obtained, and images
      can be reformatted into multiple planes from a single data set. High-contrast
      imaging can be accomplished by using three-dimensional (3D) turbo-fast low-angle
      shot (FLASH) or magnetization prepared rapid acquisition gradient-echo (MP RAGE)
      techniques with gadolinium contrast enhancement. Finally, CSF flow dynamics
      within the subarachnoid space and within cystic lesions can be elucidated with
      phase-contrast techniques. Judicious selection of these methods and other
      innovative MR techniques is necessary to maximize the potential of MR in
      diagnosis of spinal disease.

PMID- 8141020
TI  - Detection of intracranial abnormalities in patients with chronic fatigue
      syndrome: comparison of MR imaging and SPECT.
AB  - OBJECTIVE: Chronic fatigue syndrome is a recently characterized condition of
      unknown origin that is manifested by fatigue, flulike complaints, and neurologic
      signs and symptoms, including persistent headache, impaired cognitive abilities,
      mood disorders, and sensorimotor disturbances. This syndrome can be difficult to
      diagnose clinically or by standard neuroradiologic tests. We performed MR imaging
      and single-photon emission computed tomography (SPECT) in patients with chronic
      fatigue syndrome to compare the usefulness of functional and anatomic imaging in
      the detection of intracranial abnormalities. SUBJECTS AND METHODS: Sixteen
      patients who fulfilled the Centers for Disease Control, British, and/or
      Australian criteria for chronic fatigue syndrome had MR and SPECT examinations
      within a 10-week period. Axial MR and SPECT scans were analyzed as to the number
      and location of focal abnormalities by using analysis of variance with the
      Student-Newman-Keuls option. MR imaging findings in patients with chronic fatigue
      syndrome were compared with those in 15 age-matched control subjects, and SPECT
      findings in the patients with chronic fatigue syndrome were compared with those
      in 14 age-matched control subjects by using Fisher's exact test. The findings on
      MR and SPECT scans in the same patients were compared by using the Wilcoxon
      matched-pairs signed-ranks test. RESULTS: MR abnormalities consisted of foci of
      T2-bright signal in the periventricular and subcortical white matter and in the
      centrum semiovale; there were 2.06 foci per patient, vs 0.80 foci per control
      subject. MR abnormalities were present in eight (50%) of 16 patients, compared
      with three (20%) of 15 age-matched control subjects. Neither of these differences
      reached significance, although the power of the study to detect differences
      between groups was small. Patients with chronic fatigue syndrome had
      significantly more defects throughout the cerebral cortex on SPECT scans than did
      normal subjects (7.31 vs 0.43 defects per subject, p < .001). SPECT abnormalities
      were present in 13 (81%) of 16 patients, vs three (21%) of 14 control subjects (p
      < .01). SPECT scans showed significantly more abnormalities than did MR scans in
      patients with chronic fatigue syndrome (p < .025). In the few patients who had
      repeat SPECT and MR studies, the number of SPECT abnormalities appeared to
      correlate with clinical status, whereas MR changes were irreversible. CONCLUSION:
      SPECT abnormalities occur more frequently and in greater numbers than MR
      abnormalities do in patients with chronic fatigue syndrome. SPECT may prove to be
      useful in following the clinical progress of patients with this syndrome.

PMID- 8141021
TI  - Osteomyelitis.

PMID- 8141022
TI  - SPECT imaging of the brain: comparison of findings in patients with chronic
      fatigue syndrome, AIDS dementia complex, and major unipolar depression.
AB  - OBJECTIVE: Chronic fatigue syndrome is an illness of unknown origin that begins
      abruptly with a flulike state and has symptoms suggesting both a chronic viral
      encephalitis and an affective disorder. We compared single-photon emission
      computed tomography (SPECT) scans of patients with chronic fatigue syndrome with
      those of patients with AIDS dementia complex and unipolar depression. SUBJECTS
      AND METHODS: We used 99mTc-hexamethylpropyleneamine oxime to examine 45 patients
      with chronic fatigue syndrome, 27 patients with AIDS dementia complex, and 14
      patients with major unipolar depression. Scans of 38 healthy persons were used as
      controls. Comparison of regional defects between groups, as well as midcerebral
      uptake indexes (an objective measure of global radionuclide uptake), was
      performed by using analysis of variance with the Student-Newman-Keuls option.
      Correlation between the number of regional defects and the midcerebral uptake
      index was determined by using the Spearman rank-correlation test. RESULTS:
      Patients with AIDS dementia complex had the largest number of defects (9.15 per
      patient) and healthy patients had the fewest defects (1.66 per patient). Patients
      with chronic fatigue syndrome and depression had similar numbers of defects per
      patient (6.53 and 6.43, respectively). In all groups, defects were located
      predominantly in the frontal and temporal lobes. The midcerebral uptake index was
      found to be significantly lower (p < .002) in the patients with chronic fatigue
      syndrome (.667) and patients with AIDS dementia complex (.650) than in patients
      with major depression (.731) or healthy control subjects (.716). Also, a
      significant negative correlation was found between the number of defects and
      midcerebral uptake index in patients with chronic fatigue syndrome and AIDS
      dementia complex, but not in depressed patients or control subjects. CONCLUSION:
      These findings are consistent with the hypothesis that chronic fatigue syndrome
      may be due to a chronic viral encephalitis; clinical similarities between chronic
      fatigue syndrome and depression may be due to a similar distribution and number
      of defects in the two disorders.

PMID- 8141023
TI  - Neonatal subependymal cysts detected by sonography: prevalence, sonographic
      findings, and clinical significance.
AB  - OBJECTIVE: Cranial sonography in neonates occasionally shows subependymal cysts.
      These cysts may be due to a variety of pathologic disorders, but they also occur
      as an "isolated" condition without an obvious cause in some patients. Assessment
      of the clinical significance of these lesions has been difficult because of the
      limited duration of follow-up, the informal nature of neurodevelopmental
      evaluation, and the heterogeneous cohort of patients previously reported.
      Accordingly, the purposes of this study were to provide more complete and longer
      neurodevelopmental followup and to describe the prevalence and sonographic
      characteristics of isolated subependymal cysts detected on cranial sonograms in
      neonates. MATERIALS AND METHODS: In a 4 1/2-year period, more than 4000 cranial
      sonograms were obtained at our institution. We retrospectively determined that 17
      neonates (59 studies) had sonographic evidence of an isolated subependymal cyst.
      A high-resolution real-time mechanical sector transducer was used to obtain the
      sonograms. No subjects had clinical or sonographic evidence of intercurrent
      hemorrhage, infarct, infection, or congenital abnormalities. Neurodevelopmental
      outcome was independently determined. In particular, premature infants who
      weighed less than 1500 g at birth were longitudinally assessed by a
      multidisciplinary developmental team. A general quotient was derived in nine
      subjects by using the Griffith Mental Developmental Scales. RESULTS: Subependymal
      cysts were often tear shaped, 2-11 mm in size, and located either at the
      caudothalamic groove or along the anterior aspect of the caudate nucleus. Most
      subjects (n = 15) who had the cysts were born prematurely (mean gestational age,
      31 weeks; range, 25-34 weeks). Results of follow-up were available in 14 infants
      2-41 months old (mean, 22 months; median, 21 months). Development was considered
      to be normal in 13 of the 14 subjects; one term infant referred because of mild
      dysmorphic features had a mild global delay. The general quotient for corrected
      age, determined in nine subjects, had a mean of 111 (range, 103-120; normal, >
      83). Fifteen neonates had at least two cranial sonographic examinations. In seven
      patients, serial examinations showed that cysts had resolved or diminished in
      size (on average 23 weeks after the initial sonographic study). In the other
      eight, no change in the size of the cyst was observed, but the mean interval
      between the first and last sonograms was only 14 days. CONCLUSION: Cranial
      sonograms of neonates occasionally show isolated subependymal cysts, usually in
      premature infants. In most cases, no serious neurodevelopmental complications
      occur. Many cysts resolve after a variable period.

PMID- 8141024
TI  - Subdural hematoma overlooked on a CT scan of the paranasal sinuses.

PMID- 8141025
TI  - Neurofibroma manifested by spinal subarachnoid hemorrhage.

PMID- 8141026
TI  - Diagnosis of peritonsillar abscess: value of intraoral sonography.
AB  - OBJECTIVE: Clinical differentiation of peritonsillar abscess from peritonsillar
      cellulitis can be difficult and often relies on blind needle aspiration of the
      tonsillar fossa to locate pus. The objective of this study was to establish a
      noninvasive and reliable sonographic technique for differentiating peritonsillar
      abscess from peritonsillar cellulitis in equivocal cases and to thereby avoid
      unnecessary needle aspiration. SUBJECTS AND METHODS: The study population
      included three healthy volunteers and 18 patients with clinically suspected
      peritonsillar abscess. The tonsils were assessed by using transcutaneous and
      intraoral sonography. RESULTS: The tonsils were visualized on both transcutaneous
      and intraoral sonograms in all three volunteers and in 16 patients. In one
      patient, the tonsils were not visualized on transcutaneous imaging; intraoral
      imaging showed cellulitis. In another patient, the intraoral examination was
      unsuccessful, whereas transcutaneous sonograms showed normal tonsils. On the
      basis of findings on transcutaneous sonograms, tonsils were considered normal in
      seven patients. Subsequent intraoral sonograms showed peritonsillar abscesses in
      four and peritonsillar cellulitis in two. Intraoral imaging was unsuccessful in
      one patient. On the basis of findings on transcutaneous sonograms, nine patients
      were thought to have peritonsillar cellulitis. Subsequent intraoral sonograms
      confirmed cellulitis in four and showed peritonsillar abscess in five.
      Transcutaneous sonography showed one peritonsillar abscess that was confirmed by
      findings on intraoral sonography. Surgical confirmation of sonographic findings
      was obtained in 12 of 18 patients; nine of 10 peritonsillar abscesses had
      surgical drainage, and three of seven cases of peritonsillar cellulitis had a
      dry, blind needle aspiration. CONCLUSION: These results show that enlarged
      tonsils can be visualized with transcutaneous sonography, but intraoral
      sonography is necessary to adequately define the heterogeneous or cystic nature
      of a peritonsillar abscess. Intraoral sonography is a useful, simple, and well
      tolerated noninvasive technique that can be used to accurately differentiate
      peritonsillar abscess from peritonsillar cellulitis in clinically equivocal
      cases. This technique eliminates the need for blind needle aspiration of the
      tonsillar fossa before surgical drainage. Intraoral sonography also can be used
      to monitor patients' responses after treatment.

PMID- 8141027
TI  - Differentiation of benign and malignant cervical lymph nodes with color Doppler
      sonography.
AB  - OBJECTIVE: This study proposed to evaluate the efficacy of color Doppler
      sonography in detecting possible differences in blood flow patterns between
      malignant and benign cervical lymph nodes. SUBJECTS AND METHODS: During a period
      of 12 months, the palpable cervical lymph nodes of 48 untreated patients were
      prospectively evaluated with color Doppler sonography and Doppler flow wave
      analysis. Histopathologic diagnoses were obtained by sonographically guided fine
      needle aspiration biopsy and/or excisional biopsy. RESULTS: We found 16 benign
      lymph nodes (four were tuberculous lymphadenitis, four were reactive hyperplasia,
      and eight were unspecified) and 32 malignant lymph nodes (13 were squamous cell
      carcinomas, nine were adenocarcinomas, four were small-cell carcinomas, three
      were lymphomas, and three were miscellaneous). Color Doppler flow patterns were
      seen in six (38%) of the 16 benign lymph nodes and in 29 (91%) of the 32
      malignant lymph nodes. Twenty-six (81%) of the 32 malignant lymph nodes had
      abnormal flow patterns, with resistance indexes less than 0.6. However, three
      (19%) of the 16 benign lymph nodes also had abnormal flow patterns, and only
      seven (54%) of 13 squamous cell carcinomas had abnormal flow patterns.
      CONCLUSION: Color Doppler sonography has limited clinical value in
      differentiating malignant from benign cervical lymph nodes and in obviating
      biopsy.

PMID- 8141028
TI  - Diagnosis of pulmonary complications associated with lung transplantation in
      children: value of CT vs histopathologic studies.
AB  - OBJECTIVE: The purpose of this study was to compare the CT findings with those of
      histopathologic studies to determine if CT can be used to differentiate between
      the pulmonary parenchymal complications that occur in children after lung
      transplantation. MATERIALS AND METHODS: Seventeen children who underwent 14
      bilateral and three single lung transplantations were studied. The study
      population included nine girls and eight boys 2-16 years old (mean, 11 years). CT
      scans were examined for evidence of interlobular septal thickening, air-space
      consolidation, ground-glass opacities, nodules, bronchial dilatation, decreased
      vascularity, and pleural effusions. Thirty-one histopathologic diagnoses from 25
      transbronchial biopsies were available for comparison with CT findings. The final
      histopathologic diagnoses were acute rejection (n = 10), chronic rejection (n =
      6), infection (n = 7), nonspecific findings (n = 4), and no abnormalities (n =
      4). RESULTS: No significant difference was noted in the CT findings in patients
      with acute rejection, chronic rejection, and infection. CONCLUSION: In this
      limited study of children, CT findings were not helpful in differentiating
      between the different parenchymal pulmonary complications associated with lung
      transplantation. On the basis of these preliminary findings, we recommend caution
      in suggesting specific diagnoses based on CT scans without histologic proof.

PMID- 8141029
TI  - CT findings in inflammatory bowel disease in children.
AB  - CT adds valuable information in the assessment of inflammatory bowel diseases in
      children. Although early mucosal changes are best shown by barium studies,
      extramucosal and extraintestinal abnormalities are best visualized with CT. CT
      can be used to differentiate the various extramucosal abnormalities that may have
      similar appearances on barium studies, including bowel wall thickening, abscess,
      phlegmon, or adenopathy. Although many inflammatory conditions of bowel may have
      similar appearances on CT scans, a careful analysis of the appearance of the
      bowel wall and the associated extraintestinal abnormalities, combined with a
      review of the clinical and laboratory data, enables a specific diagnosis to be
      made in many cases.

PMID- 8141030
TI  - Metallic foreign bodies in the orbits of patients undergoing MR imaging:
      prevalence and value of radiography and CT before MR.
AB  - OBJECTIVE: The purpose of this study was to measure the prevalence of metallic
      foreign bodies in the orbits of 15,024 patients who were scheduled for MR imaging
      during a 4-year period and to determine if screening by plain radiography, CT, or
      both before MR imaging is efficacious. MATERIALS AND METHODS: Records of 15,024
      patients scheduled for MR imaging were reviewed. A total of 1593 patients who had
      identified themselves as being at risk for an intraorbital metallic foreign body
      had undergone plain radiography or CT of the orbits. Plain radiographs and/or CT
      scans of patients reported as having orbital metal were reviewed to confirm the
      presence of a metallic foreign body and to identify its location. RESULTS:
      Metallic foreign bodies were discovered in 40 patients. Six of these patients had
      impaired vision in the involved eye. Ten patients had a metallic foreign body in
      or near the orbit but well away from the globe and were thought to be at low risk
      for movement of the foreign body as a result of MR imaging. The other 24 patients
      had metallic foreign bodies adjacent to or within the globe and were thought to
      be at risk for movement of the metallic foreign body as a result of MR imaging.
      CONCLUSION: The prevalence of intraorbital metallic foreign bodies in our study
      population was low (0.27%). Even in those patients identified as being at risk,
      the prevalence was only 2.5%. Based on the number of MR examinations performed
      annually in the United States and on data indicating that no radiographic
      screening is performed at 5% of institutions, we extrapolate that more than 2400
      patients with intraorbital metallic foreign bodies have undergone MR imaging
      since 1986 without report of injury. These data allow us to infer that the risk
      of eye damage for patients who have intraorbital metal is low and that
      radiographic screening before MR imaging is not needed as often as it is done.

PMID- 8141031
TI  - Re: Metallic foreign bodies in the orbits of patients undergoing MR imaging:
      prevalence and value of radiography and CT before MR.

PMID- 8141032
TI  - Interactive videodisc for teaching radiology.
AB  - This article reviews the development and current use of the interactive videodisc
      as a tool for teaching radiology. Inherent advantages of the videodisc include
      large image capacity with random access, ability to incorporate motion video,
      ability to overlay arrows and other graphics on images, quality of images, speed
      of retrieval and display, and ease of management of images.

PMID- 8141033
TI  - The history of radiology at the University of California, Los Angeles.

PMID- 8141034
TI  - Exacerbation of myasthenia gravis by contrast media.

PMID- 8141035
TI  - Untoward effects of MR imaging.

PMID- 8141036
TI  - Tailored timing as a critical factor in CT angiography.

PMID- 8141037
TI  - Kudos for PR and more about words.

PMID- 8141038
TI  - Toe prosthesis in an Egyptian human mummy.

PMID- 8141039
TI  - Sequential MR enhancement pattern in normal pituitary gland and in pituitary
      adenoma.
AB  - PURPOSE: To measure and evaluate the temporal enhancement characteristics of the
      normal pituitary gland and pituitary adenoma. METHODS: Thirty healthy subjects
      and 10 patients with sellar pituitary adenomas were studied prospectively using
      dynamic MR imaging with a 5- or 10-sec temporal resolution during a bolus
      injection of gadolinium. RESULTS: Qualitative visual analysis demonstrated a
      consistent sequential pattern of pituitary enhancement in which the posterior
      lobe enhanced earlier than the anterior lobe by approximately 35 sec.
      Quantitative analysis revealed that posterior lobe enhancement occurred 9.8 +/-
      1.5 sec (mean +/- SEM) before the anterior lobe in healthy subjects, whereas
      tumor enhancement occurred significantly before the anterior lobe but only
      slightly before the posterior lobe in patients with adenomas. CONCLUSION: The
      sequential enhancement pattern of the normal pituitary gland was found to be
      consistent with its vascular anatomy. In contrast to previous reports, pituitary
      adenomas were found to enhance earlier than the anterior lobe. These results
      suggest that pituitary adenomas have a direct arterial blood supply, similar to
      that of the posterior pituitary lobe.

PMID- 8141040
TI  - On low back pain.

PMID- 8141041
TI  - MR of acute autonomic and sensory neuropathy.

PMID- 8141042
TI  - Imaging white matter tracts and nuclei of the hypothalamus: an MR-anatomic
      comparative study.
AB  - PURPOSE: To evaluate the MR appearance of the hypothalamus and its associated
      white matter tracts. METHODS: Coronal and sagittal spin-echo images were obtained
      in cadaver brains. Gross and histologic sections were made of the cadaver brains.
      The size, shape, signal intensity, course, and pattern of structures in the
      hypothalamic region were identified in MR images by comparison with the anatomic
      sections. RESULTS: The mamillary bodies, paraventricular zone of hypothalamic
      nuclei, postcommissural fornix, mammillothalamic fasciculus, and anterior
      commissure were identified on the MR images. CONCLUSION: This study suggests
      that, with MR imaging of sufficiently high resolution, some of the tracts and
      nuclei in the hypothalamus may be identified.

PMID- 8141043
TI  - Blood flow in major cerebral arteries measured by phase-contrast cine MR.
AB  - PURPOSE: To measure mean blood flow in individual cerebral arteries (carotid,
      basilar, anterior cerebral, middle cerebral, and posterior cerebral) using a cine
      phase contrast MR pulse sequence. METHODS: Ten healthy volunteers (22 to 38 years
      of age) were studied. The cine phase-contrast section was positioned
      perpendicular to the vessel of interest using oblique scanning planes. This pulse
      sequence used a velocity encoding range of 60 to 250 cm/sec. From the velocity
      and area measurements on the cine images, mean blood flow was calculated in
      milliliters per minute and milliliters per cardiac cycle. In the same subjects,
      transcranial Doppler measurements of blood velocity in these same vessels were
      also obtained. RESULTS: There was no difference in blood flow in the paired
      cerebral arteries. Carotid arteries had mean blood flow in the range of 4.8 +/-
      0.4 ml/cycle, the basilar artery 2.4 +/- 0.2 ml/cycle, the middle cerebral artery
      1.8 +/- 0.2 ml/cycle, the distal anterior cerebral artery 0.6 +/- 0.1 ml/cycle,
      and the posterior cerebral artery 0.8 +/- 0.1 ml/cycle. Overall, there was poor
      correlation between MR-measured and transcranial Doppler-measured peak velocity.
      CONCLUSION: Although careful attention to technical detail is required, mean
      blood flow measurements in individual cerebral vessels is feasible using a cine
      phase-contrast MR pulse sequence.

PMID- 8141044
TI  - MR of the inner ear in patients with Cogan syndrome.
AB  - PURPOSE: To determine whether the bony and soft-tissue obliterations of the
      intralabyrinthine fluid spaces reported in pathologic studies of patients with
      Cogan syndrome can be detected with MR or CT. METHODS: The inner ears of six
      patients with Cogan syndrome were studied. High-resolution CT was performed in
      five patients; all six patients were studied with MR, including T1-weighted spin
      echo images with and without gadolinium administration, T2-weighted spin-echo
      images, and three-dimensional Fourier transform constructive interference in
      steady state images. RESULTS: In two patients, small calcified obliterations were
      detected on CT but the three-dimensional Fourier transform constructive
      interference in steady state images revealed more extensive soft-tissue
      obliteration in five of the six patients. High signal inside the membranous
      labyrinth on precontrast T1-weighted images and contrast enhancement inside the
      membranous labyrinth on the postcontrast T1-weighted images were seen in one
      patient. CONCLUSIONS: The study showed that calcific obliteration and soft-tissue
      obliteration of the intralabyrinthine fluid spaces in patients with Cogan
      syndrome can be demonstrated radiologically and that soft-tissue obliteration is
      more frequent than calcified obliteration. MR detected the intralabyrinthine
      disease far more frequently than did CT. The three-dimensional Fourier transform
      constructive interference in steady state sequence proved to be the most
      sensitive MR sequence. Hyperintensity inside the membranous labyrinth on the
      precontrast T1-weighted images and enhancement on the contrast-enhanced T1 images
      were less frequent and probably represent leakage through the abnormal
      labyrinthine membrane from active disease.

PMID- 8141045
TI  - The congenital bilateral perisylvian syndrome: imaging findings in a multicenter
      study. CBPS Study Group.
AB  - PURPOSE: To describe the neuroimaging findings and the clinical features in
      patients with the congenital bilateral perisylvian syndrome. PATIENTS AND
      METHODS: Evaluation including history, general and neurologic examinations,
      electroencephalogram, chromosomal studies, and imaging data were reviewed in 31
      patients. Pathologic material was available in two patients. RESULTS: All
      patients had similar neurologic dysfunction, primarily pseudobulbar paresis.
      Dysarthria and severe restriction of tongue movements were present in all. Motor
      milestones were delayed in 75% of the patients and language milestones in all.
      Mild to moderate intellectual deficits were documented in 75% of patients (full
      scale IQ = 70). Pyramidal signs were observed in 70%. Seizures were present in
      87% and were intractable to medical therapy in half of this group. MR revealed
      bilateral perisylvian and perirolandic malformations with exposure of the insula.
      The malformations were symmetrical in 80% of cases. Pathologic correlation
      revealed four layered polymicrogyria in the affected areas. CONCLUSIONS: The
      congenital bilateral perisylvian syndrome is a homogeneous clinical-radiologic
      entity. The underlying abnormality is probably polymicrogyria.

PMID- 8141046
TI  - MR of brain involvement in progressive facial hemiatrophy (Romberg disease):
      reconsideration of a syndrome.
AB  - PURPOSE: To gain further insight into the pathogenesis of progressive facial
      hemiatrophy, a sporadic disease of unclear etiology characterized by shrinking
      and deformation of one side of the face. METHODS: We investigated possible brain
      involvement. MR of the head and face was performed in three female patients with
      progressive facial hemiatrophy. The central-nervous-system findings were
      correlated to a clinical protocol and a review of the literature. RESULTS: One
      patient with epilepsy had abnormal brain findings confined to the cerebral
      hemisphere homolateral to the facial hemiatrophy. These consisted of
      monoventricular enlargement, meningocortical dysmorphia, and white-matter
      changes. CONCLUSIONS: These MR findings, and corresponding neuroradiologic data
      disclosed by the review, indicate that homolateral hemiatrophy occasionally
      occurs in a subgroup of patients with progressive facial hemiatrophy. The MR
      features do not seem consistent with an underlying simple or nutritive atrophic
      process. We propose chronic localized meningoencephalitis with vascular
      involvement as a possible underlying cause of the occasional brain involvement in
      progressive facial hemiatrophy.

PMID- 8141047
TI  - Dehiscence of the lamina papyracea of the ethmoid bone: CT findings.
AB  - PURPOSE: To describe the CT findings characterizing dehiscence of the lamina
      papyracea. METHODS: Axial and coronal CT scanning of the paranasal sinuses was
      performed on 783 patients. RESULTS: Dehiscence of the lamina papyracea was noted
      incidentally in six patients. In all cases dehiscence was characterized by
      protrusion of orbital fat through a gap in the anterior ethmoid. The posterior
      limit of the dehiscence was always the basal lamella. The anterior limit varied.
      CONCLUSION: CT scans are often taken to detect polyps or assess chronic
      sinusitis. Awareness of dehiscence of the lamina papyracea is important to avoid
      misdiagnosis as infectious or tumoral process and possible injury of the orbit
      during endoscopic surgery.

PMID- 8141048
TI  - Metastatic adenocarcinoma to the brain: MR with pathologic correlation.
AB  - PURPOSE: To describe the appearance on T2-weighted scans of metastatic
      adenocarcinoma to the brain and to show that the hypointensity frequently
      associated with these lesions is not related to the presence of mucin, blood
      products, iron, or calcium. METHODS: The MR scans of 14 patients with metastatic
      adenocarcinoma to the brain were reviewed retrospectively. The signal intensity
      on T2-weighted scans of the solid enhancing portion of the tumors was compared
      with white matter. Histologic examination of the surgical specimens included
      special stains to search for calcium, mucin, and iron. RESULTS: Eight of nine
      surgical and all six nonsurgical lesions were either iso- or hypointense to white
      matter on T2-weighted scans. There was no correlation with tumor histology or the
      presence of mucin, blood products, iron, or calcium. CONCLUSIONS: The presence of
      a hypointense intraaxial mass on T2-weighted scans strongly suggests the
      possibility of metastatic adenocarcinoma. The MR appearance is not explained by
      the presence of mucin, blood products, iron, or calcium. This phenomenon most
      likely reflects the relaxation parameters of the tissue from which the metastasis
      arose.

PMID- 8141049
TI  - Benign glial cysts of the pineal gland: unusual imaging characteristics with
      histologic correlation.
AB  - PURPOSE: To describe the spectrum of MR and CT findings in clinically symptomatic
      pineal cysts and to determine whether there are certain diagnostic imaging
      features that allow one to distinguish a benign pineal cyst from other neoplasms
      of the pineal region. METHODS: MR and CT scans of 19 patients with clinically
      symptomatic pineal cysts were retrospectively reviewed. Age range was 15 to 46
      years with a mean age of 28 years. There were five male and 14 female patients.
      RESULTS: Presenting features included headache (15 patients), diplopia (four),
      nausea and vomiting (four), papilledema (four), seizure (three), Parinaud
      syndrome (two), ataxia (one), and hemiparesis (one). All cysts were resected or
      biopsied to provide histopathologic confirmation of the diagnosis. Preoperative
      diagnoses included pineal neoplasm (14 of 19), pineal cyst (3 of 19), and dermoid
      cyst (2 of 19). The lesions ranged from 0.8 to 3.0 cm, with a mean diameter of
      1.6 cm. Three cysts showed fluid/fluid levels consistent with hemorrhage.
      Slightly less than half (9 of 19) had evidence of hydrocephalus. The MR signal
      changes were variable but typically demonstrated low signal on T1-weighted images
      and high signal on T2-weighted images. More than half (7 of 12) demonstrated
      enhancement with gadolinium. Calcification of the cyst wall was observed in only
      four of nine patients who had CT studies but identified histologically in all
      cases. CONCLUSION: The MR appearance of benign pineal cysts is variable, ranging
      from that of an uncomplicated cystic mass to a mass associated with hemorrhage,
      enhancement, or hydrocephalus. This variability may make them indistinguishable
      from other pineal-region tumors.

PMID- 8141050
TI  - Deceptively normal MR in early infantile Krabbe disease.
AB  - The authors present two cases of 5-month-old children with early infantile Krabbe
      disease studied by CT and MR. Both infants had characteristic CT scans for the
      disease consisting of symmetric hyperdensity involving the cerebellum, thalami,
      caudate, corona radiata, and brain stem. One of the infants had a deceptively
      normal initial MR examination, with dramatic progression of the white-matter
      disease over the following 4 months.

PMID- 8141051
TI  - Mamillary body enhancement on MR as the only sign of acute Wernicke
      encephalopathy.
AB  - We report a case of Wernicke encephalopathy in which the only sign of acute
      disease was enhancement of the mamillary bodies. This case demonstrates the
      utility of gadolinium enhancement at MR imaging as a means of diagnosing or
      confirming the syndrome of Wernicke encephalopathy even in the absence of atrophy
      or T2 abnormalities within the diencephalon and mesencephalon.

PMID- 8141052
TI  - Toxic leukoencephalopathy after inhalation of poisoned heroin: MR findings.
AB  - Retrospective MR studies of four patients with neurologic symptoms after
      inhalation of contaminated heroin vapor revealed extensive, typically symmetrical
      lesions in the white matter of the cerebrum, cerebellum, and midbrain. Selective
      involvement of the corticospinal tract, the solitary tract, and the lemniscus
      medialis also has been found.

PMID- 8141053
TI  - Millard-Gubler syndrome.

PMID- 8141054
TI  - Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain
      abnormalities.
AB  - We report a case of thrombotic thrombocytopenic purpura evaluated by MR. Multiple
      hyperintense foci on the T2-weighted images, observed principally in the brain
      stem and in the region of the basal nuclei, and neurologic signs disappeared
      after 15 days of therapy.

PMID- 8141055
TI  - Carotid sinus syndrome secondary to iatrogenic dissection of the carotid artery.

PMID- 8141056
TI  - Hemangiomas and vascular malformations of the head and neck: MR characterization.

PMID- 8141057
TI  - Epidural pneumatosis: not necessarily benign.

PMID- 8141058
TI  - More association of linear sebaceous nevus syndrome and unilateral
      megalencephaly.

PMID- 8141059
TI  - Erroneous placement of side indicators of brain CT.

PMID- 8141060
TI  - Middle cranial fossa not temporal fossa.

PMID- 8141061
TI  - Localized cerebral proton MR spectroscopy in HIV infection and AIDS.
AB  - PURPOSE: To document differences in the cerebral proton MR spectra of patients
      with early and late stages of human immunodeficiency virus (HIV) infection.
      METHOD: We studied the relative N-acetyl-aspartate (NAA) levels by localized
      proton spectroscopy of the parietooccipital region of the brain in 43 HIV
      seropositive patients, including 26 with an acquired immunodeficiency syndrome
      (AIDS)-defining diagnosis, and in eight control subjects. RESULTS: Reduced
      relative NAA levels were shown in those HIV-1-seropositive patients: 1) with AIDS
      against HIV-1-seropositive patients without AIDS (P < .04); 2) with HIV-1
      associated cognitive/motor complex against neurologically healthy patients (P <
      .007); 3) with encephalopathic changes on MR against those with normal imaging (P
      < .001); and 4) on follow-up against their results on initial study (P < .03).
      CONCLUSIONS: By clinical (Centers for Disease Control classification) and
      radiologic (MR evidence of white-matter disease) criteria indicating late-stage
      HIV infection, reduced relative levels of NAA have been demonstrated.
      Spectroscopic abnormalities can be quantitatively tracked with time. This paper
      demonstrates the clinical use of detecting NAA as a putative in vivo measure of
      the neuronal loss that has been demonstrated in postmortem studies of patients
      with AIDS. This neuronal loss, which is believed to underlie the HIV-1-associated
      cognitive/motor complex, is thought to be attributable directly or indirectly to
      the presence of HIV in the brain. Proton spectroscopy may serve as a quantitative
      noninvasive indicator of this aspect of cerebral involvement in HIV disease.

PMID- 8141062
TI  - Lesion enhancement in radio-frequency spoiled gradient-echo imaging: theory,
      experimental evaluation, and clinical implications.
AB  - PURPOSE: To investigate the lesser lesion conspicuity after gadolinium contrast
      infusion with radio-frequency spoiled gradient-echo (SPGR) sequences relative to
      conventional T1-weighted spin-echo techniques. METHODS: The influences of
      repetition time, echo time, and flip angle on spin-echo and SPGR signal were
      studied with mathematical modeling of the image signal amplitude for
      concentrations of gadopentetate dimeglumine solute from 0 to 10 mM. Predictions
      of signal strength were verified in vitro by imaging of a doped water phantom.
      The effects of standard (0.1 mmol/kg) and high-dose (0.3 mmol/kg) gadoteridol on
      spin-echo and SPGR images were also investigated in three patients. RESULTS: The
      measured amplitude of undoped water and the rate of increase of doped water
      signal with increasing gadopentetate concentration (slope) for spin-echo
      600/11/1/90 degrees (repetition time/echo time/excitations/flip angle) and SPGR
      (600/11/190 degrees) were similar and exceeded those of SPGR (35/5/145 degrees).
      Greater increases in SPGR doped water signal and its slope were produced by
      increasing TR than by varying echo-time or flip angle. The subjective lesion
      conspicuity and measured lesion contrast at 0.3 mmol/kg were greater with spin
      echo (600/11/1/90 degrees) than with SPGR (35/5/145 degrees) in all three
      patients; the measured lesion enhancement was similar for both techniques in two
      patients and decreased for SPGR in the third patient. CONCLUSIONS: The phantom
      studies suggest that the short repetition time of 35 msec, typically used in
      clinical SPGR imaging, is largely responsible for a reduced signal amplitude and
      a diminished rate of increase of signal with increasing gadopentetate
      concentration, relative to spin-echo. Phantom and clinical studies suggest that
      the dose of paramagnetic agent required to achieve SPGR lesion conspicuity with
      short repetition time comparable with spin-echo would have to be higher than the
      dose in current clinical use.

PMID- 8141063
TI  - Contrast MR of the brain after high-perfusion cardiopulmonary bypass.
AB  - PURPOSE: To study the efficacy of contrast MR imaging in the evaluation of
      central nervous system complications in the cardiopulmonary bypass patient and
      attempt to explain their pathophysiology based on the MR appearance and the
      cardiopulmonary bypass protocol. METHOD: Nineteen patients were prospectively
      studied with contrast MR examinations the day before and 3 to 7 days after
      cardiopulmonary bypass, to determine the nature, extent, and number of new
      postoperative MR abnormalities. Cardiopulmonary bypass parameters used in our
      institution included: membrane oxygenation, arterial filtration with a pore size
      of 25 microns, and a relatively high perfusion rate to produce a cardiac index of
      2.0 to 2.5 L/min per m2. RESULTS: The preoperative noncontrast MR examination
      showed age-related changes and/or signs of ischemia in 60% of patients on the day
      before surgery. However, there was no abnormal enhancement or new T2
      abnormalities on any postoperative MR examination to suggest hypoperfusion or
      emboli. None of the 19 patients developed overt neurologic deficits
      postoperatively. Review of the cardiopulmonary bypass protocol used indicated
      significant variations in technique at different institutions. CONCLUSION:
      Contrast MR imaging demonstrated no new abnormalities in patients after
      cardiopulmonary bypass performed with strict in-line arterial filtration and
      relatively high perfusion. MR imaging is feasible in the early postoperative
      period after cardiopulmonary bypass and may offer a convenient method for
      evaluation of the neurologic impact of technical factors associated with
      cardiopulmonary bypass.

PMID- 8141064
TI  - Comparison of lesion enhancement on spin-echo and gradient-echo images.
AB  - PURPOSE: To compare lesion enhancement after injection of gadopentetate
      dimeglumine on spin-echo and gradient-echo T1-weighted images. METHODS: A total
      of 48 contrast-enhancing intracranial lesions were evaluated using a spin-echo
      and two gradient-echo T1-weighted pulse sequences. Percent contrast, contrast-to
      noise, and signal-to-noise measurements were made on the spin-echo T1-weighted,
      three-dimensional gradient-echo, and multiplanar gradient-echo sequences.
      RESULTS: The measurements were somewhat different for the following categories of
      lesions: extraaxial, intraaxial with edema, and intraaxial without edema. The
      latter group provided the greatest diagnostic challenge: three of 19 such lesions
      1 cm in size or smaller could not be identified on three-dimensional gradient
      echo images, and one could not be identified on multi-planar gradient-echo
      images. The spin-echo T1-weighted sequence demonstrated significantly higher
      percent contrast (P < .05) and greater contrast to noise (P < .03) than either
      gradient-echo sequence for these small intraaxial lesions without edema. For
      extraaxial and intraaxial lesions with edema, percent C was similar for spin-echo
      T1-weighted and three-dimensional gradient-echo images, while contrast to noise
      was greater for spin-echo T1-weighted images. This reflected greater tissue noise
      with gradient-echo sequences. CONCLUSION: The T1-weighted spin-echo sequence was
      preferred for detecting the full spectrum of contrast-enhancing lesions of the
      central nervous system.

PMID- 8141065
TI  - Assessment of MR image deformation for stereotactic neurosurgery using a tagging
      sequence.
AB  - A tagging sequence is used to assess MR image deformations before a stereotactic
      neurosurgical procedure, in a test model and in two patients. This pulse sequence
      super-imposes narrow parallel orthogonal tag lines on an image, which can be used
      as an internal reference frame. Image deformation is directly related to surface
      area variations in the squares produced by the tagging-sequence pulses. Small
      spatial deformations of the tags can be detected on the images used for measuring
      stereotactic-target spatial coordinates. A threshold of 2 SD guarantees that the
      distortion is smaller than one pixel.

PMID- 8141066
TI  - Heparin administration and monitoring for neuroangiography.
AB  - PURPOSE: To establish the optimal protocol of heparin administration during
      interventional neuroradiology. METHODS: We assessed 100 cases of
      neuroangiography, including endovascular surgery, and measured activated
      coagulation time before and 5 minutes after heparin administration, and before
      and 5 minutes after protamine neutralization. In some cases actual heparin
      concentration was assayed using a chromogenic substrate technique. RESULTS: The
      actual plasma heparin concentration significantly correlated with the dose of
      heparin administered intravenously (r = .98; P < .0001) and changes in activated
      coagulation time (r = .85; P < .0001). The change in activated coagulation time
      significantly correlated with the dose of heparin injected intravenously (r =
      .54, P < .0001). The ratio of change in activated coagulation time significantly
      correlated with time elapsed after heparin administration (r = -.70, P < .0001).
      CONCLUSIONS: The activated coagulation time is useful in monitoring
      administration and neutralization of heparin during neuroangiography, and a bolus
      injection of 60 U/kg heparin should be adequate to carry out neuroangiography for
      75 minutes safely, even for endovascular surgery.

PMID- 8141067
TI  - Diagnostic applications of simultaneously acquired dual-isotope single-photon
      emission CT scans.
AB  - PURPOSE: To report the development and validation of a technique of dual tracer
      single-photon emission CT brain imaging using technetium-99m
      hexamethylpropyleneamine oxime and iodine-123 iodoamphetamine agents and the
      application of this technique in patients with a variety of diagnoses. METHODS:
      Contamination between the two isotopes' energy windows was calculated by opening
      both energy windows while scanning a group of patients using a single isotope. To
      compare uniformity of I-123 down-scatter, Tc-99m studies were performed both
      before and after the administration of I-123 in five of 24 dual studies. The 24
      patients studied with the dual-isotope technique were evaluated during
      acetazolamide testing, trial balloon occlusion, or embolization of an
      arteriovenous malformation. RESULTS: In a dual acquisition, average count
      contamination of an I-123 study by Tc-99m was less than 1% of the total I-123
      counts, and contamination of a Tc-99m study by I-123 was approximately 12% of the
      total Tc-99m counts. Tc-99m studies performed both before and after the
      administration of I-123 demonstrated that contaminating counts do not adversely
      affect scan interpretation. Dual-tracer scans were completed in all 24 patients,
      10 of whom showed changes after intervention. CONCLUSIONS: Dual-tracer single
      photon emission CT brain scans of adequate diagnostic quality are possible using
      Tc-99m and I-123.

PMID- 8141068
TI  - Preoperative spinal angiography for lateral extracavitary approach to thoracic
      and lumbar spine.
AB  - PURPOSE: To establish the safety, efficacy, and value of preoperative angiography
      in the surgical management of thoracic and lumbar spine disease, in which it is
      important to avoid injury to the artery of Adamkiewicz or other vessels that
      supply the spinal cord. METHODS: Sixty-one patients were evaluated primarily
      using digital subtraction angiography, low-osmolar or nonionic contrast agents,
      selective catheterization limited to the region of disease, and careful
      angiographic techniques. RESULTS: Two minor (small hematomas of the groin) and no
      major complications of angiography were encountered. Arterial supply to the
      spinal cord was identified in 22 patients. In 17 patients (77%), the arterial
      supply was in the region of planned surgery. In each of these patients the
      surgical approach was altered, either by dictating the use of a posterior
      surgical approach (four patients) or by altering the side of the lateral
      extracavitary approach (13 patients). CONCLUSION: Spinal angiography is a safe
      preoperative examination for thoracic and lumbar spine surgery. It is
      specifically useful when the lateral extracavitary surgical approach to spinal
      cord decompression and fusion (which predictably interrupts the terminal end
      arterial blood supply to the spinal cord, if present) is planned.

PMID- 8141069
TI  - Percutaneous puncture of the external carotid artery or its branches after
      surgical ligation.
AB  - PURPOSE: To describe the technique and results of percutaneous puncture of the
      external carotid artery or one of its branches distal to a surgical arterial
      ligation. METHODS: Forty-three patients underwent 64 embolization attempts by
      percutaneous arterial puncture distal to an external carotid artery ligation. The
      punctured arteries were the trunk of the external carotid artery in 31 patients,
      the internal maxillary artery in nine, the facial artery in nine, the lingual
      artery in eight, the occipital artery in four, and the superficial temporal
      artery in three. RESULTS: In 64 attempts 57 were successful in one session, six
      were successful in two sessions, and one failed. Puncture-related complications
      were eight spontaneously resolving hematomas and six asymptomatic punctures of
      the internal carotid artery. CONCLUSION: After surgical ligation of the external
      carotid artery or its branches, arterial puncture above the ligation allowed
      selective catheterization and endovascular occlusion of vascular lesions.

PMID- 8141070
TI  - Percutaneous vertebroplasty guided by a combination of CT and fluoroscopy.
AB  - We describe the technique of percutaneous vertebroplasty using methyl
      methacrylate. We injected under the guidance of CT and fluoroscopy a group of 10
      patients with back pain caused by a variety of vertebral lesions including severe
      osteoporosis (n = 4), hemangiomas (n = 5) and metastasis (n = 1). Over varying
      periods of follow-up (ranging from 4 to 17 months) none of the injected vertebral
      bodies demonstrated compression. All patients had relief of back pain; none had
      complications related to the technique. We emphasize that the efficacy of this
      technique in preventing vertebral collapse could not be evaluated in this small
      sample; a well-controlled study would be required to determine the proper
      indications and efficacy of this treatment.

PMID- 8141071
TI  - Sensitivity and prognostic value of early CT in occlusion of the middle cerebral
      artery trunk.
AB  - PURPOSE: To investigate the incidence and prognostic value of local brain
      swelling, the extent of parenchymal hypodensity, and the hyperdense middle
      cerebral artery sign as shown by CT within the first 5 hours after the onset of
      symptoms in patients with angiographically proved middle cerebral artery trunk
      occlusions. METHODS: Fifty-three patients were studied prospectively with CT 46
      to 292 minutes (median, 120; mean, 134 +/- 59) after symptom onset and scored
      clinically at admission and 4 weeks later. All patients were treated with
      recombinant tissue plasminogen activator (30 to 100 mg). RESULTS: Early CT showed
      parenchymal hypodensity in 43 patients (81%), local brain swelling in 20 patients
      (38%), and hyperdensity of the middle cerebral artery trunk in 25 patients (47%).
      Hypodensity covering more than 50% of the middle cerebral artery territory had an
      85%, local brain swelling a 70%, and the hyperdense middle cerebral artery sign a
      32% positive predictive value for fatal clinical outcome. Specificity of these
      findings for fatal outcome was 94%, 83%, and 51%, respectively, and sensitivity
      was 61%, 78% and 44%, respectively. CONCLUSIONS: Early CT in acute middle
      cerebral artery trunk occlusion is highly predictive for fatal clinical outcome
      if there is extended hypodensity or local brain swelling despite aggressive
      therapeutic attempts such as thrombolysis or decompressive surgery.

PMID- 8141072
TI  - The effect of intracarotid nonionic contrast media on the blood-brain barrier in
      acute hypertension.
AB  - PURPOSE: To determine whether acute hypertension (HT) is a risk factor for damage
      to the blood-brain barrier in carotid angiography with nonionic contrast media.
      METHODS: Anesthetized rats received intravenous injections of technetium-99m
      pertechnetate and horseradish peroxidase. Two groups of rats received metaraminol
      to raise their blood pressure to between 165 and 190 mmHg peak systolic and then
      received intracarotid injections of saline or iopamidol. Two other groups
      remained normotensive and received intracarotid injections of saline or
      iopamidol. Animals were perfused with a fixative solution and their brains
      removed. Activity of extravasated Tc-99m-pertechnetate was determined to assess
      blood-brain barrier breakdown. Brains were then sectioned, treated
      histochemically to visualize extravasated horseradish peroxidase, and ranked
      visually according to horseradish peroxidase staining. RESULTS: Extravasation of
      both tracers was significantly greater in the hypertensive group that received
      contrast media than in the other three groups. CONCLUSIONS: Acute hypertension
      potentiates the blood-brain barrier-damaging effects of nonionic contrast media
      during carotid angiography in rats.

PMID- 8141073
TI  - Molecular studies of the calcium antagonist binding site on calcium channels.
AB  - Currently available calcium antagonists act primarily on L-type calcium channels.
      Composed of 5 subunits, this ion channel is markedly more complicated than the
      potassium and sodium channels. Most of the data that have emerged over the past
      year have concerned the alpha subunit. The secondary structure of this subunit
      includes 4 repeating motifs; each motif contains 6 membrane-spanning helices,
      designated S1 through S6. The dihydropyridine (e.g., nifedipine) binding site is
      most likely situated primarily in motif 4 and the phenylalkylamine (e.g.,
      verapamil) binding site is on motif 4 in an intracellular region. The
      benzothiazepine (e.g., diltiazem) binding site is also located on the alpha 1
      subunit, but its precise location has not been determined. The transmembrane
      helices S5 and S6 of each motif have been proposed as the "wall" of the actual
      ion channel.

PMID- 8141074
TI  - Comparison of the prognostic values of ischemia during daily life and ischemia
      induced by treadmill exercise testing.
AB  - Although silent ischemia is common in patients with stable coronary artery
      disease (CAD), controversy surrounds the issue regarding the most appropriate
      method for detection. Routinely performed exercise tolerance testing provides
      important prognostic information. However, ambulatory electrocardiographic
      monitoring (AEM) has the distinct advantage of enabling evaluation of silent
      ischemia during daily life. Although numerous AEM studies have found a greater
      occurrence of silent ischemia than symptomatic ischemia in patients with stable
      angina pectoris, the independent prognostic value of AEM findings has not been
      definitively established. Several recent studies have addressed the question of
      whether AEM supplies additional information beyond that obtained from exercise
      testing. The results of these studies revealed that myocardial ischemia during
      daily life that is detected by AEM provides additional and independent prognostic
      information in patients with stable CAD who have evidence of ischemia during
      exercise testing.

PMID- 8141075
TI  - An overview of risk assessment in coronary artery disease.
AB  - Risk assessment is a central activity in virtually all aspects of the examination
      and treatment of patients. Methods to standardize this process and improve its
      accuracy can only improve the quality of medical care. Since health care is
      undergoing reform in this country, it seems likely that physicians will
      increasingly need objective justification for their decision making. Risk
      assessment models offer a potentially useful tool. The Duke Treadmill Score is
      well-validated and clinically useful for risk assessment in patients with either
      established or suspected coronary artery disease for whom the desirability of
      additional invasive testing must be determined. One of the major goals of risk
      assessment is to identify the low-risk patients for whom no additional testing is
      required. Whereas multiple valid strategies for accomplishing this exist, there
      is no consensus on the optimal approach. Cost-containment pressures may indicate
      the use of exercise testing as the preferred initial strategy in patients who are
      able to exercise and have an interpretable electrocardiogram. Exercise nuclear
      testing could thus be reserved for patients in the intermediate-risk group for
      whom the additional accuracy of these latter tests would provide a more precise
      risk-stratification estimate. For patients unable to exercise, a pharmacologic
      stress test (such as echocardiography with dobutamine or an adenosine isonitrile
      study) would be an acceptable alternative.

PMID- 8141076
TI  - Myocardial reperfusion injury: role of oxygen radicals and potential therapy with
      antioxidants.
AB  - Experimental studies have demonstrated that reperfusion is associated with a host
      of distinctive pathophysiologic derangements, the most important of which are
      reperfusion arrhythmias, transient mechanical dysfunction or "myocardial
      stunning," and cell death. Reperfusion arrhythmias and myocardial stunning occur
      in experimental animals after transient ischemia followed by reperfusion, and
      there is considerable evidence that these derangements also develop in humans,
      although the existence of malignant reperfusion arrhythmias in humans remains
      uncertain. Reperfusion arrhythmias and myocardial stunning can be considered
      manifestations of sublethal, reversible cellular injury. The pathogenesis of
      reperfusion arrhythmias and stunning has not been conclusively established;
      however, there is considerable evidence that generation of oxygen radicals and
      perturbations of calcium homeostasis play an important role. Antioxidants and
      calcium antagonists have been shown to mitigate these manifestations of
      reperfusion injury. In contrast, the likelihood of lethal reperfusion-induced
      injury remains highly controversial. Although many studies have reported
      reduction of infarct size with antioxidants, numerous others have failed to
      reproduce these results. Consequently, intense controversy persists regarding
      whether oxygen radicals contribute to extending cell death following reperfusion
      and whether reperfusion itself causes cell death. Neither the resolution of this
      controversy nor the availability of clinical therapies to reduce reperfusion
      induced cell death is likely in the near future.

PMID- 8141077
TI  - Therapeutic approaches to postoperative ischemia. The Study of Perioperative
      Ischemia Research Group.
AB  - Previous attempts to identify predictors of cardiac complications, an important
      cause of postoperative morbidity and mortality following non-cardiac surgery,
      have focused mainly on the patient's preoperative state. Our research group,
      however, has found that adverse cardiac outcome correlates most highly with the
      appearance of at least 1 ischemic episode determined by continuous ambulatory
      electrocardiographic monitoring (AEM) in the early postoperative period. Such
      early postoperative ischemia conferred (1) a greater than 9-fold increased risk
      of experiencing in-hospital cardiac death, nonfatal myocardial infarction, or
      postoperative unstable angina, and (2) a greater than 2-fold increased long-term
      (2-year) risk of cardiac death, myocardial infarction, or angina requiring
      coronary angioplasty or coronary artery bypass grafting (CABG). Additionally, 5
      predictors of such postoperative ischemia were identified: left ventricular
      hypertrophy, diabetes mellitus, hypertension, definite coronary artery disease,
      and preoperative digoxin use. These findings suggest that patients who are at
      high risk for postoperative myocardial ischemia warrant more intensive
      postoperative monitoring. Moreover, since such ischemia is potentially
      reversible, the testing of strategies designed to prevent or manage postoperative
      ischemia appears warranted and is discussed. Our group also has established the
      usefulness of AEM for identifying ischemic episodes in patients undergoing CABG.
      However, patients who require cardiopulmonary bypass present unique problems
      regarding the interpretation of AEM recordings. We describe guidelines for the
      interpretation of AEM results obtained under these conditions and suggest
      criteria based on the degree of interpretability for patient inclusion in future
      studies.

PMID- 8141078
TI  - Programmed Outcome Research Teams (PORTs) and implications for clinical practice.
AB  - The spiraling cost of health care has created a health care crisis. Concerns
      about the appropriate use of expensive medical technologies have been heightened
      by health services research studies that demonstrate widespread and dramatic
      geographic variability in the use of tests and procedures. The Agency for Health
      Care Policy and Research has funded 14 Programmed Outcome Research Teams (PORTs)
      targeted at specific disease entities. The PORT in ischemic heart disease is
      examining 2 principal decisions--which patients should undergo cardiac
      catheterization and, following catheterization, how patients should be treated.
      The PORT in ischemic heart disease combines information from the literature, 18
      databases, and patient preference studies in models examining these 2 decisions.
      The databases have also been used to develop statistical models that estimate
      outcomes with different therapies. The benefit of a therapy in a population can
      be illustrated using an empirically derived, marginal value curve that describes
      the expected improvement in outcome (e.g., survival) that accrues with additional
      procedures performed in patients who are most likely to benefit.

PMID- 8141079
TI  - Advisory Group reports on silent myocardial ischemia, coronary atherogenesis, and
      cardiac emergencies. Council for Myocardial Ischemia and Infarction.

PMID- 8141080
TI  - Platelet activation in stable coronary artery disease.
AB  - To elucidate the role of physical activity in the pathogenesis of acute ischemic
      syndromes in patients with coronary artery disease (CAD), we hypothesized that
      platelet activation occurs when coronary blood flow velocity and shear stress
      increase across an atherosclerotic vascular bed. We measured platelet aggregation
      by using angiologic catheterization to obtain simultaneous samples of whole blood
      from the coronary sinus and the aorta while at rest, 2 minutes after the onset of
      rapid atrial pacing, and 10 minutes after termination of pacing. Of 82
      consecutive patients included in our study, 36 had stenosis of the left coronary
      artery, 12 had stenosis of the right coronary artery only, and 34 had no evidence
      of CAD. Samples taken at rest revealed no arteriovenous difference in platelet
      aggregation between patients with CAD and those without CAD. In patients with
      significant stenosis (> or = 50%) of the left coronary artery, atrial pacing
      caused platelet aggregation to increase in samples from the coronary sinus (64 +/
      9% increase; p < 0.01) but not in blood from the aorta (2 +/- 8% decrease;
      difference not significant). This increase was transient, with aggregation
      returning almost to resting values 10 minutes after pacing ended. Atrial pacing
      elicited no change in platelet aggregation in samples from either the coronary
      sinus or aorta of patients with nonsignificant stenosis (< 50%) of the left
      coronary artery, patients with significant stenosis of the right coronary artery
      only, and patients free of CAD. Thus, under resting conditions, no evidence of
      platelet activation across the coronary bed was seen regardless of CAD
      status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141081
TI  - Impact of preintervention intravascular ultrasound imaging on transcatheter
      treatment strategies in coronary artery disease.
AB  - Preintervention intravascular ultrasound (IVUS) imaging was performed in 313
      target lesions in 301 patients. Revascularization strategy intended before
      imaging was compared with the treatment actually performed; there was a change in
      therapy in 124 lesions (40%) in 121 patients (40%). This included: (1) assessment
      of lesion severity leading to revascularization when none had been planned (n =
      20, 6%), (2) avoiding surgery or catheter-based revascularization that had
      originally been planned (n = 21, 7%), and (3) assessment of lesion composition
      leading to a change in revascularization strategy (n = 20, 6%) or for selecting
      the revascularization strategy (n = 63, 20%). Nine of these 121 patients were
      referred for coronary artery bypass graft surgery. IVUS minimal lumen diameter
      correlated well with angiography (r = 0.83); however, a disagreement was the
      reason for deciding to perform or not to perform revascularization in 41 lesions
      (13%). IVUS assessment of target lesion calcification, eccentricity and unusual
      morphology were the reasons for changing or selecting specific devices: (1)
      concentric and eccentric lesions with significant superficial calcium were
      treated with rotational atherectomy, excimer laser angioplasty or surgery; (2)
      eccentric lesions that did not contain significant superficial calcium were
      treated with directional atherectomy; (3) dissections and true aneurysms were
      treated with stent placement even if calcified; (4) thrombus-containing lesions
      in vein grafts were treated with thrombolytic therapy or extraction atherectomy,
      or both; and (5) fibrotic vein graft lesions were treated with balloon
      angioplasty or stent placement.

PMID- 8141082
TI  - Effects of cyclic flexion of coronary arteries on progression of atherosclerosis.
AB  - The purpose of this investigation was to test the hypothesis that cyclic flexion
      of the coronary arteries contributes to the progression of atherosclerotic
      plaques. Coronary arteriograms were evaluated in 33 unselected patients who
      underwent 2 studies over a period of 25 +/- 16 months (mean +/- SD). Among the 33
      patients, 103 plaques were identified. Plaques that showed progression were
      compared with plaques that showed no progression. The angle of flexion that
      occurred during systole at the site of the plaque was measured on the first
      arteriogram. In comparing progression versus no progression, the interval between
      arteriograms was 29 +/- 18 versus 23 +/- 14 months (p = NS) and percent stenosis
      at the first arteriogram was 42 +/- 28 versus 45 +/- 19% (p = NS). Percent
      stenosis at the time of the second arteriogram among plaques that progressed was
      78 +/- 21%, and by definition, it remained 45 +/- 19% among those that did not
      progress. Among arteries with plaques that showed a progression of stenosis, the
      angle of flexion during systole was 19 +/- 13 degrees versus 9 +/- 15 degrees
      among arteries with plaques that did not progress (p < 0.01). Linear regression
      showed that the correlation of the angle of flexion with percent change of
      stenosis was relatively low (r = 0.32) but statistically significant (p < 0.005).
      Mathematic modeling of flexible and stiff plaques showed stresses approximately
      1.5 to 1.9 times greater with 20 degrees than with 10 degrees flexion. Stresses
      due to flexion were usually greatest proximal and distal to the plaque along the
      subendothelial layer of the inner wall of the curved vessel. Data show that the
      angle of cyclic flexion, and consequently the stresses due to cyclic flexion of
      the artery were greatest in the region of plaques that progressed over the period
      of observation. Such stresses may have contributed to tissue damage of fatigue
      resulting in a more rapid progression of the atheromatous plaques.

PMID- 8141083
TI  - Influence of gender in the therapeutic management of patients with acute
      myocardial infarction in Israel. The Israeli Thrombolytic Survey Group.
AB  - A national study was performed in early 1992 in the 25 operating coronary care
      units in Israel, which enabled the assessment of whether the therapeutic
      management of patients with acute myocardial infarction was affected by patient
      gender. During a 2-month period, 1,014 consecutive patients with acute myocardial
      infarction were hospitalized. Thrombolytic therapy was given to 47% of men (362
      of 769), and 43% of women (106 of 245) (p = NS). After adjustment for age, no
      gender differences in the administration of thrombolytic therapy were noted (odds
      ratio 0.95; 95% confidence interval 0.73-1.23). Coronary angiography was more
      frequently performed in men (22%) than in women (16%) (p < 0.05). However, no
      gender differences in the use of angioplasty or coronary bypass surgery performed
      during the index hospitalization were found (10% in men, and 8% in women). The
      main reasons for ineligibility for thrombolytic therapy were: late hospital
      arrival, absence of qualifying ST-T changes on admission electrocardiogram, and
      contraindications to thrombolytic therapy. Hospital death was significantly lower
      in patients receiving thrombolytic therapy (37 of 456; 8%) than in those excluded
      from thrombolysis (70 of 540;13%) (p < 0.01). This difference was significant for
      men, but not for women. The 1-year postdischarge mortality was 4% in patients
      treated compared with 12% in those ineligible for thrombolysis (p < 0.01). This
      significant difference persisted among men and women.

PMID- 8141084
TI  - Intracranial hemorrhage risk and new thrombolytic therapies in acute myocardial
      infarction.
AB  - Thrombolytic therapy for acute myocardial infarction (AMI) has reduced mortality
      at the expense of additional intracranial hemorrhages. To determine whether this
      trade-off has been optimized, a decision analysis was performed using pooled data
      to determine the further reductions in mortality required to justify increased
      intracranial hemorrhage rates from more potent thrombolytic and adjunctive
      antithrombotic regimens that intravenous streptokinase. Pooled data from large
      clinical trials suggest that streptokinase has a 0.07% nonfatal intracranial
      hemorrhage rate. Approximately 54% of these result in major/moderate disability
      and 46% in recovery or minor residual. The early mortality rate in all AMI
      patients treated with thrombolytic therapy is 9.8%; it is 6.8% in patients with
      inferior wall AMI and 17.9% in elderly patients. If a new thrombolytic regimen
      provides a 1% absolute reduction in early mortality compared with streptokinase
      therapy, approximately a > or = 3.2% nonfatal intracranial hemorrhage rate is
      justified to obtain this survival benefit. For a 10% relative reduction in
      mortality risk, the maximal acceptable nonfatal intracranial hemorrhage rates are
      2.2% for inferior wall AMI, 3.2% for all patients and 5.9% for elderly patients.
      Whereas intracranial hemorrhage is a catastrophic complication of thrombolytic
      therapy in the treatment of patients with AMI, thrombolytic regimens that result
      in significantly higher rates of intracranial hemorrhage than those observed with
      streptokinase may be preferable at surprisingly smaller additional reductions in
      mortality. In addition to evaluating new thrombolytic and antithrombotic
      regimens, this analysis, in conjunction with models that predict patient-specific
      intracranial hemorrhage risks and mortality benefits from thrombolytic therapy,
      can provide a framework for matching AMI patients with optimal thrombolytic
      regimens.

PMID- 8141085
TI  - Dipyridamole stress echocardiography in patients with severe left main coronary
      artery narrowing. Echo Persantine International Cooperative (EPIC) Study Group-
      Subproject "Left Main Detection".
AB  - From a population of 2,698 patients (579 evaluated early after an uncomplicated
      acute myocardial infarction) who underwent dipyridamole echocardiography testing
      (DET) and subsequent coronary angiography, left main (LM) stenosis > or = 50% was
      present in 73 (61 men and 12 women, mean age 62 +/- 8 years). These 73 patients
      were compared with a control group comprising 100 consecutive coronary patients
      without LM disease. Both groups were similar regarding mean age, sex, incidence
      of previous myocardial infarction, left ventricular function at rest, and
      severity of coronary artery disease by the number of diseased vessels excluding
      the LM. The proportion of patients receiving antianginal therapy during DET was
      higher in the LM than in the non-LM group (32 vs 14%; p < 0.01). No major
      complication (severe hypotension, sustained arrhythmia, myocardial infarction or
      death) occurred during DET. Of 73 patients with LM disease, 68 had positive DET
      (sensitivity 93%), dipyridamole time was 7.1 +/- 3.8 minutes, and the rest-peak
      stress variation in dipyridamole wall motion score index (1 = normal to 4 =
      dyskinesia, in an 11-segment model) was 0.37 +/- 0.23; 14 patients (19%) were
      resistant to aminophylline and needed nitrates to resolve ischemia. In the non-LM
      group, DET was positive in 72% (p < 0.001 vs LM), with a longer dipyridamole time
      (9.6 +/- 5.2 minutes; p < 0.001 vs LM), lower rest-peak stress wall motion score
      index variation (0.29 +/- 0.25; p < 0.05 vs LM), and less frequent antidote
      resistance (1%; p < 0.001 vs LM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141086
TI  - Safety of dobutamine-atropine stress echocardiography in patients with suspected
      or proven coronary artery disease.
AB  - The purpose of this study was to establish the safety of high-dose dobutamine
      atropine stress echocardiography in patients with suspected or proven coronary
      artery disease. Six hundred fifty consecutive examinations were completed. Mean
      age of patients was 61 years; 300 had a previous myocardial infarction. Heart
      rate increased from 73 to 129 beats/min during stress testing, blood pressure did
      not change significantly (from 140/81 to 150/80 mm Hg). Atropine was added to
      dobutamine in 239 patients when no ischemia was induced with dobutamine alone and
      the peak heart rate was < 85% of the theoretical maximal heart rate. Atropine was
      more frequently administered to patients taking beta blockers (77 vs 27%, p <
      0.001). New wall motion abnormalities developed in 243 patients (37%).
      Significant or symptomatic cardiac tachyarrhythmias, or both, developed during 24
      examinations: 1 patient developed ventricular fibrillation, 3 patients developed
      sustained ventricular tachycardia, 12 patients experienced nonsustained
      ventricular tachycardia (< 10 beats) and 8 patients had paroxysmal atrial
      fibrillation. Cardiac arrhythmias were more frequent in patients with a history
      of ventricular arrhythmias (ventricular tachycardia and fibrillation) (odds ratio
      9.9, 2.0 to 45) or left ventricular dysfunction at rest (wall motion score >
      1.12) (odds ratio 2.9, 1.1-7.6), but not associated with atropine addition. No
      death or myocardial infarction occurred. The full dose was not given to 13
      patients despite absence of signs or markers of ischemia for limiting side
      effect, yielding an overall feasibility of the stress test of 98%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141087
TI  - Waist circumference and abdominal sagittal diameter: best simple anthropometric
      indexes of abdominal visceral adipose tissue accumulation and related
      cardiovascular risk in men and women.
AB  - The amount of abdominal visceral adipose tissue measured by computed tomography
      is a critical correlate of the potentially "atherogenic" metabolic disturbances
      associated with abdominal obesity. In this study conducted in samples of 81 men
      and 70 women, data are presented on the anthropometric correlates of abdominal
      visceral adipose tissue accumulation and related cardiovascular disease risk
      factors (triglyceride and high-density lipoprotein cholesterol levels, fasting
      and postglucose insulin and glucose levels). Results indicate that the waist
      circumference and the abdominal sagittal diameter are better correlates of
      abdominal visceral adipose tissue accumulation than the commonly used waist-to
      hip ratio (WHR). In women, the waist circumference and the abdominal sagittal
      diameter also appeared more closely related to the metabolic variables than the
      WHR. When the samples were divided into quintiles of waist circumference, WHR or
      abdominal sagittal diameter, it was noted that increasing values of waist
      circumference and abdominal sagittal diameter were more consistently associated
      with increases in fasting and postglucose insulin levels than increasing values
      of WHR, especially in women. These findings suggest that the waist circumference
      or the abdominal sagittal diameter, rather than the WHR, should be used as
      indexes of abdominal visceral adipose tissue deposition and in the assessment of
      cardiovascular risk. It is suggested from these data that waist circumference
      values above approximately 100 cm, or abdominal sagittal diameter values > 25 cm
      are most likely to be associated with potentially "atherogenic" metabolic
      disturbances.

PMID- 8141088
TI  - Posterior ("atypical") atrioventricular junctional reentrant tachycardia.
AB  - The aim of this study was to characterize a relatively rare type of
      atrioventricular (AV) junctional reentrant tachycardia (AVJRT). Posterior AVJRT
      is a type of AV nodal tachycardia in which the site of earliest atrial activation
      is posterior to the AV node near the coronary sinus orifice. The mechanism of
      this tachycardia is not well understood. The characteristics of posterior AVJRT
      (n = 15) were compared with those of anterior ("common") AVJRT (n = 146) and
      supraventricular tachycardia using single posterior septal accessory pathways (n
      = 13). During posterior AVJRT, the AH interval was longer than the retrograde
      conduction time (His to earliest atrial activity) in 11 cases (73%), indicating
      that these tachycardias were not fast-slow types of AVJRT. The mean
      ventriculoatrial (VA) interval in posterior AVJRT (93 +/- 41 ms) was longer than
      in anterior AVJRT (11 +/- 20 ms; p < 0.005), but was similar to that in
      tachycardias using accessory pathways (106 +/- 16 ms; p = NS). The site of
      earliest atrial activation during posterior AVJRT was similar to that in
      tachycardias using accessory pathways. In all cases of accessory pathway-mediated
      tachycardia, atrial activation could be advanced by ventricular extrastimuli
      delivered coincident with the His deflection, but atrial activation was not
      advanced in any case of posterior AVJRT unless the extrastimulus was delivered >
      80 ms before the His deflection. Anterograde conduction was similar in the
      posterior and anterior AVJRT groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141089
TI  - Mechanism of angina pectoris in patients with systemic hypertension and normal
      epicardial coronary arteries by arteriogram.
AB  - Patients with arterial hypertension frequently have angina pectoris despite a
      normal coronary angiogram. This angina pectoris syndrome often goes along with an
      impaired coronary vasodilator reserve. The aim of the study was to find out
      whether an impaired coronary flow reserve is associated with electrographic signs
      of transient myocardial ischemia. Forty-three hypertensive patients not taking
      cardiovascular medication were studied with 24-hour Holter monitoring. Coronary
      blood flow and resistance were measured before and after intravenous
      administration of dipyridamole (0.5 mg/kg body weight). Coronary reserve was
      determined as the relation of coronary resistance before and after dipyridamole.
      For control purposes 9 normotensive subjects were studied with the same protocol.
      Hypertensive patients with ST-segment depressions (n = 31) had a significantly
      impaired coronary reserve (2.3 +/- 0.5) compared with normotensive subjects (4.9
      +/- 1.0, p < 0.01). Coronary reserve in hypertensive patients without ST-segment
      depressions was only slightly impaired (4.0 +/- 1.8). Arterial pressure and left
      ventricular mass did not differ between hypertensive patients with and without ST
      segment depressions. Left ventricular mass had no effect on coronary reserve. It
      is concluded that neither left ventricular hypertrophy nor arterial pressure were
      determinants for ST-segment depressions. Consequently primary functional and
      structural alterations on the level of the microcirculation appear to be
      responsible for the occurrence of transient ischemic episodes in the Holter
      electrocardiogram.

PMID- 8141090
TI  - Disparate structural effects on left and right ventricles by angiotensin
      converting enzyme inhibitors and calcium antagonists in essential hypertension.
AB  - Reduced left ventricular (LV) mass and wall thicknesses with angiotensin
      converting enzyme (ACE) inhibitors and calcium antagonists occur in essential
      hypertension. Experimental studies have shown that reduction in LV mass is
      related to hemodynamic as well as nonhemodynamic factors that may influence LV
      and also right ventricular (RV) structure. Sixty-eight patients with essential
      hypertension were studied echocardiographically 4 to 8 weeks after
      antihypertensive therapy was initiated. LV dimensions and wall thicknesses, as
      well as RV free wall thickness, were measured using 2-dimensionally guided
      techniques. Patients were divided in 2 groups: those receiving either ACE
      inhibitors or calcium antagonists. This short-term therapeutic period produced
      similar hemodynamic changes and reductions in LV mass in both groups. In these 2
      groups of patients, we found opposite effects in RV free wall thickness. Thus, RV
      wall thickness increased from 0.44 +/- 0.02 to 0.56 +/- 0.02 cm (p < 0.01) after
      therapy in the calcium antagonist group, whereas no change was found in the ACE
      inhibitor group (0.36 +/- 0.04 vs 0.34 +/- 0.04). These structural changes
      suggest that ACE inhibitors and calcium antagonists produce dissimilar effects on
      cardiac cell growth and growth reversal, which may be mediated through different
      nonhemodynamic effects after short-term therapy.

PMID- 8141091
TI  - Recovery of the right ventricle after single-lung transplantation in pulmonary
      hypertension.
AB  - Single-lung transplantation has been successfully performed in patients with
      pulmonary fibrosis and emphysema. In contrast, patients with end-stage pulmonary
      hypertension (either primary or secondary to Eisenmenger's syndrome) have
      conventionally been offered heart-lung transplantation. The rationale underlying
      this approach is that chronic pulmonary hypertension results in irreversible
      right ventricular dilatation and failure. Recovery of the right ventricle has
      previously been reported after thromboendarterectomy for chronic large-vessel
      pulmonary embolism, correction of atrial septal defect or mitral valve
      replacement. The evolution of right ventricular morphology and function after
      lung transplantation has not been previously described. This study examines the
      reversibility of right ventricle dysfunction following normalization of pulmonary
      artery pressure after single-lung transplantation in 4 patients with pulmonary
      hypertension. Cardiac function was assessed using electrocardiography,
      echocardiography and radionuclide angiography. Pulmonary hemodynamic
      measurements, including pulmonary artery pressure and pulmonary vascular
      resistance, decreased in all patients after single-lung transplantation.
      Electrocardiographic changes observed were leftward shift in the QRS axis, and a
      decrease in P-wave amplitude and in right ventricular force. Echocardiographic
      examination revealed decreased right atrial, right ventricular and tricuspid
      valve annular dimensions, normalization of septal motion, and decreased tricuspid
      regurgitation. Thus, improved pulmonary hemodynamics after single-lung
      transplantation for pulmonary vascular disease results in reversal of right heart
      dilatation and dysfunction, and improved myocardial performance. The extent of
      right ventricular dysfunction beyond which recovery is unlikely to occur has yet
      to be determined.

PMID- 8141092
TI  - Simulation of intraoperative visualization of cardiac structures and study of
      dynamic surgical anatomy with real-time three-dimensional echocardiography.
AB  - Most prior efforts of 3-dimensional (3-D) reconstruction of echocardiographic
      images have focused on quantitation of ventricular size and function. The
      resulting images have been displayed in the wire mesh format. Recently, a method
      for 3-D transesophageal echocardiography using a computer-controlled probe that
      acquires parallel tomographic slices has been described. This technique provides
      dynamic 3-D volume-rendered images of the heart. This study was designed to
      determine if surgical visualization of intracardiac anatomy could be simulated
      using this imaging system. Data acquired from 8 patients with congenital and
      acquired heart disease were analyzed. Real-time 3-D images of the cardiac
      chambers and valves were obtained. Images of the cardiac pathology including
      fibrocalcific nodules on the aortic valve, mitral valve endocarditis, rheumatic
      mitral stenosis, and an ostium secundum atrial septal defect were displayed in 3
      dimensions that simulated surgical exposure of these structures. These 3-D
      representations of cardiac anatomy were in some ways superior to standard
      intraoperative visualization in that they demonstrated the heart as a dynamic
      structure, as opposed to the empty, nonbeating heart observed while on
      cardiopulmonary bypass. In conclusion, 3-D images of cardiac structures as seen
      by the surgeon intraoperatively can be provided using a computer-driven
      tomographic transesophageal echocardiographic probe. This imaging system can be
      potentially useful in the planning and evaluation of cardiac surgery. Technical
      improvements such as 3-D representation of flow jets, the ability to manipulate
      images to simulate cardiac surgery, and on-line reconstruction can make this a
      powerful tool in the future.

PMID- 8141093
TI  - Comparison of histopathologic coronary lesions obtained from directional
      atherectomy in stable angina versus acute coronary syndromes.

PMID- 8141094
TI  - Alleviation of cocaine-induced coronary vasoconstriction with intravenous
      verapamil.

PMID- 8141095
TI  - Effect of long-term diltiazem administration on serum lipids in post-myocardial
      infarction survivors. Multicenter Diltiazem Post-Infarction Trial Research Group.

PMID- 8141096
TI  - Correlation of improved left ventricular ejection fraction recovering from supine
      exercise with resting function in anterior wall healed myocardial infarction.

PMID- 8141097
TI  - Angina-free time on the treadmill as an alternate method for evaluating
      antianginal therapy. Veterans Affairs ACME Investigators.

PMID- 8141098
TI  - Role of transesophageal echocardiography in the assessment of patients with
      composite aortic grafts for therapy in acute aortic dissection.

PMID- 8141099
TI  - Identification of intracoronary thrombus and demonstration of thrombectomy by
      intravascular ultrasound imaging.

PMID- 8141100
TI  - In memoriam: Herman K. Hellerstein, MD--physician, scientist, scholar, teacher
      and friend.

PMID- 8141101
TI  - A cooperative randomized controlled study of adjuvant chemoendocrine therapy for
      breast cancer in Japan.
AB  - A randomized trial was carried out in 55 Japanese institutions to examine the
      significance of postoperative adjuvant chemoendocrine therapy in Stages II and
      IIIA breast cancer patients after radical mastectomy. A total of 619 patients
      were entered from November 1982 to November 1984, of whom 554 were eligible.
      Patients were administered MMC (13 mg/m2) after surgery, and were randomized by
      the envelope method into either group A (ftorafur, 400 mg/m2/day; 275 patients),
      or group B (ftorafur, 400 mg/m2/day, and tamoxifen, 20 mg/day; 279 patients).
      Treatment was continued for 1 year from postoperative day 7. There were no
      significant differences between the two groups with regard to age, menopausal
      status, ER status, method of operation, stage, or number of positive lymph nodes.
      There was also no significant difference between the two groups in the 5-year
      survival and disease-free survival (DFS) rates (Kaplan-Meier method).
      Stratification by ER status, nodal status, or menopausal status produced no
      significant differences between the groups. However, postmenopausal patients and
      lymph node-positive patients who were also ER-positive showed a significantly
      higher DFS in group B. Furthermore, group B in ER-positive patients with four or
      more positive lymph nodes also had a higher survival rate.

PMID- 8141102
TI  - Moscow hospital-based proton therapy facility design.
AB  - An innovative design for a hospital-based proton therapy facility is described
      here in two versions: a single level (3600 m2) and a three-level plan (700-720
      m2). The facility is designed to have 5 to 6 treatment rooms working
      simultaneously and independently of each other. The accelerator is a 250 MeV H
      synchrotron, which produces a small external beam capable of pencil-beam scanning
      treatments. The small emittance of the beam yields cost savings in the size and
      weight of the magnets and the amount of concrete shielding. The beam delivery
      systems, including an isocentric gantry, are designed to use elements that are
      well known and thoroughly tested. Initial cost of a facility using this new
      design is estimated to be only 25-30% higher than construction of a facility
      delivering conventional photon treatments.

PMID- 8141103
TI  - The Bird's Nest Filter. An alternative to long-term oral anticoagulation in
      patients with advanced malignancies.
AB  - Thromboembolic complications are common in patients with advanced malignancies.
      For these patients anticoagulation with warfarin is often complicated by severe
      bleeding. For this reason we evaluated the safety and efficacy of the Bird's Nest
      Filter, a new device capable of preventing migration of thromboemboli to the
      pulmonary arteries through interruption of the inferior vena cava. We report a
      series of 31 unselected patients with advanced malignancies and thromboembolic
      disease in whom the filter was used in lieu of chronic full-dose warfarin
      anticoagulation. No documented cases of pulmonary emboli occurred after insertion
      of the filter. Placement of the filter was uncomplicated. Eight patients (25.8%)
      developed lower-extremity edema. Venous thrombosis distal to the filter was
      documented in six (19.4%) patients but did not require institution of heparin or
      warfarin. Two patients (6.5%) required treatment with aspirin for painful lower
      extremity thrombophlebitis. No filter migration was documented. We conclude that
      the use of the Bird's Nest Filter is an option for patients with cancer-related
      lower-extremity thrombosis who are at risk for pulmonary emboli and are poor
      candidates for full-dose systemic anticoagulation with warfarin. A prospective
      randomized trial comparing the filter and the new strategy of low-dose
      anticoagulation with warfarin will be needed to completely validate this
      approach.

PMID- 8141104
TI  - A Gynecologic Oncology Group phase II study of amonafide (NSC #308847) in
      squamous cell carcinoma of the cervix.
AB  - Twenty evaluable patients with squamous cell carcinoma of the cervix, who had
      previously received a cisplatin-containing regimen, were treated with amonafide
      300 mg/m2 over 1 hour for 5 consecutive days every 3 weeks. One partial response
      (5%) was seen. Hematologic toxicity was substantial with severe or life
      threatening events occurring as follows: leukopenia, 5 patients (25%);
      thrombocytopenia, 4 patients (20%); granulocytopenia, 2 patients (10%). One
      patient experienced acute bilateral open-angle glaucoma immediately after
      treatment, and another developed gastric ulceration with life-threatening
      gastrointestinal bleeding. In view of the low response rate and high toxicity,
      amonafide does not warrant further investigation as second-line chemotherapy in
      squamous cell carcinoma of the cervix.

PMID- 8141105
TI  - Efficacy of oral ondansetron, a selective antagonist of 5-HT3 receptors, in the
      treatment of nausea and vomiting associated with cyclophosphamide-based
      chemotherapies. Ondansetron Study Group.
AB  - We evaluated the efficacy and safety of oral ondansetron, a selective antagonist
      of 5-HT3 receptors, for the treatment of nausea and vomiting associated with
      cyclophosphamide-based chemotherapy (> 500 mg/m2). In this trial 324 chemotherapy
      naive cancer patients, mostly females with breast cancer, were randomized to
      receive either placebo or ondansetron 1 mg, 4 mg, or 8 mg three times per day for
      3 days. There were no differences in the doses of cyclophosphamide, doxorubicin,
      and methotrexate between the study groups. All ondansetron dose groups were
      superior to the placebo control group (p < .001) for all measured efficacy
      parameters (complete response, number of emetic episodes, therapeutic failures,
      need of rescue antiemetics). No emetic episodes were reported by 9 (12%), 29
      (37%), 48 (64%), and 47 (66%) of the placebo patients and the 1-mg, 4-mg, and 8
      mg dose of ondansetron patients, respectively. Nausea was reduced and food intake
      was improved for all the ondansetron groups. A more severe emetic response was
      observed in patients receiving cyclophosphamide and doxorubicin combination
      chemotherapy. In this subgroup of patients, 66%, 38%, 25%, and 16% of the placebo
      group and 1-mg, 4-mg, and 8-mg ondansetron patients, respectively, required
      rescue antiemetics. No significant toxic effects were observed in this study. A
      higher incidence of headaches and gastrointestinal complaints (constipation,
      abdominal pain) were observed in the three ondansetron groups. In conclusion,
      oral ondansetron is an effective and well-tolerated antiemetic treatment in the
      management of cancer patients receiving ambulatory cyclophosphamide-based
      chemotherapy. These results support the view that serotonin and 5-HT3 receptors
      play an important role in cyclophosphamide-induced nausea and vomiting.

PMID- 8141106
TI  - Oral ondansetron: a useful addition to the supportive care armamentarium?

PMID- 8141107
TI  - A randomized double-blind trial of ondansetron alone versus in combination with
      dexamethasone versus in combination with dexamethasone and lorazepam in the
      prevention of emesis due to cisplatin-based chemotherapy.
AB  - OBJECTIVE: To compare the effectiveness and side effects of antiemetic regimens
      using ondansetron alone (O) versus ondansetron plus dexamethasone (OD) versus
      ondansetron plus dexamethasone plus lorazepam (ODA) in the prevention of emesis
      induced by cisplatin-based chemotherapy. DESIGN: Randomized, double-blind trial.
      PATIENTS AND METHODS: In this study, 75 patients who were receiving cisplatin (60
      mg/m2) on day 1 and 5-fluorouracil (1,000 mg/m2) on day 2 to day 6 were enrolled.
      Patients were randomized to one of three treatment regimens: O, OD, or ODA. The
      patients assigned to O regimen received ondansetron 8 mg intravenously as a
      loading dose 15 minutes prior to cisplatin, then 1 mg/h continuous i.v. infusion
      (24 mg/day) for 48 hours. OD regimen consisted of ondansetron given as above plus
      dexamethasone administered at a dose of 10 mg i.v. injection every 12 hours for 3
      days. ODA regimen was OD regimen plus lorazepam administered at a dose of 0.5 mg
      orally every 6 hours for 3 days. To ensure blinding, O group patients received 10
      ml placebo-saline i.v. injection every 12 hours for 3 days, and O and OD group
      patients received placebo tablets orally every 6 hours for 3 days. RESULTS: One
      patient did not receive assigned antiemetic regimen and was excluded from the
      analysis. In the acute phase, complete control of emesis was seen in 85% of all
      patients, and there was no significant difference among the three groups (p =
      .442). Complete control of nausea during the acute phase was achieved in 10
      patients (41.2%) treated with O regimen alone, in 23 patients (92.0%) treated
      with OD regimen, and in 16 patients (64.0%) treated with ODA regimen (p < .001).
      In the delayed phase, 68% of patients who received the three-drug combination
      (ODA) and 56% of patients who received the two-drug combination (OD) obtained
      complete control of emesis, as opposed to 29% who were given ondansetron alone (p
      < .021). The incidences of headache, flushing, dry mouth, hiccups, and
      constipation were mild and tolerable and did not differ among the three groups.
      DISCUSSION: Ondansetron was very effective in the prevention of nausea and
      vomiting during the acute phase after cisplatin administration. In treating
      delayed nausea and vomiting, although the results of three regimens were still
      disappointing, the combination of ondansetron plus dexamethasone or plus
      lorazepam provided superior results. Patients who received the lorazepam
      containing regimen appeared more comfortable and less restless than those who
      were given other regimens.

PMID- 8141108
TI  - Carboplatin, epirubicin, and VP-16 chemotherapy in the treatment of small cell
      lung cancer.
AB  - In our study, 72 SCLC patients, 23 with limited and 49 with extensive disease,
      were treated with carboplatin, epirubicin, and VP-16 (CEV) chemotherapy (CBDCA
      300 mg/m2 day 1, EDX 50 mg/m2 day 1, VP-16 100 mg/m2 i.v. days 1-3, every 4
      weeks). Patients with limited disease were also subjected to concurrent "split
      course" chest radiotherapy followed by surgery in responders if they were not
      staged IIIB at diagnosis. In limited disease we obtained 96.5% objective
      responses (OR) with 52.5% complete responses (CR), a median survival of 14
      months, with 13% long-term survivors at 30 months. In extensive disease we
      obtained 83.6% OR with 28.5% CR, and a median survival of 10 months. Toxicity
      consisted mainly of manageable myelosuppression, especially for limited disease.
      These data show high activity of CEV chemotherapeutic regimen.

PMID- 8141109
TI  - Inefficacy of low-dose continuous oral etoposide in non-small cell lung cancer.
AB  - Etoposide is more active in small cell lung cancer when given over 5 days than as
      a single injection. To examine this concept further, we designed this Phase II
      study in NSCLC using continuous low-dose oral etoposide. We enrolled 19 patients
      with measurable disease and the standard eligibility criteria. 16 had no prior
      chemotherapy. Etoposide was given at a dose of 50 mg by mouth daily. The median
      duration of therapy was 63 days (14-212 days). Toxicity was mild myelosuppression
      and GI symptoms. Therapy was discontinued because of progression of disease in 13
      patients, toxicity (GI) in 3 patients; intercurrent disease, self-removal, and
      other reasons in 1 patient each. No complete or partial responses were seen (95%
      CI: 0-17.6%). The median survival after entry into the trial was 159 days (41
      571+ days). We conclude that low-dose continuous oral etoposide is a well
      tolerated but ineffective regimen in non-small cell lung cancer.

PMID- 8141111
TI  - Intracavitary brachytherapy for squamous cell carcinoma of the esophagus.
AB  - From September 1983 through January 1989, 8 patients with a diagnosis of squamous
      cell carcinoma of the esophagus AJCC stages I to III, were treated with
      intracavitary brachytherapy following external irradiation. Within 3 months after
      completion of treatment, there was radiographic evidence of complete response in
      6 of the 8 patients. None of the responders recurred locally. All the patients
      have died, with a mean survival of 17 months. One patient died of a stroke 2 1/2
      years after completion of treatments without clinical evidence of esophageal
      cancer. Treatment was well tolerated, with minimal acute toxicity, and one
      patient developed stricture at the site of tumor, which was successfully treated
      by dilatation. Addition of systemic chemotherapy to this regimen warrants
      investigation.

PMID- 8141110
TI  - An Eastern Cooperative Oncology Group phase II study of single agent DHAD, VP-16,
      aclacinomycin, or spirogermanium in metastatic pancreatic cancer.
AB  - There were 80 patients with measurable metastatic or unresectable pancreatic
      cancer randomly assigned to treatment with either DHAD, VP-16, aclacinomycin, or
      spirogermanium. There were no complete or partial responses. Two deaths from
      leukopenia occurred in patients treated with DHAD. One patient receiving
      spirogermanium experienced a seizure. No other life-threatening toxicities
      occurred. Maximal toxicities were not significantly more frequent with any
      treatment group. Median survival was 10 weeks, and median time to progression was
      only 6 weeks, with no difference among these four therapies.

PMID- 8141112
TI  - Phase II trial of 5-fluorouracil and high-dose folinic acid as first- or second
      line therapy for advanced breast cancer.
AB  - The use of leucovorin to modulate 5-fluorouracil (FUra)-mediated inhibition of
      thymidylate synthase has been shown both in vitro and in vivo to improve the
      antitumor activity of FUra. Based on the activity of this combination in
      previously untreated patients, we performed a study of FUra and high-dose
      leucovorin (HDFA) in patients with metastatic breast cancer and minimal prior
      chemotherapy. Patients were stratified by prior chemotherapy (or relapse within
      12 months of completing adjuvant chemotherapy) versus no prior chemotherapy (or
      relapse at greater than 12 months since completion of adjuvant chemotherapy).
      FUra was given daily for 5 days at 370 mg/m2/day with HDFA, 500 mg/m2/day,
      beginning 24 hours before and continuing 12 hours beyond the first and last FUra
      doses, respectively. Two objective responses occurred among 21 patients in the
      pretreated group (10%; 95% confidence interval: 1-30%). Four of 36 eligible
      patients (11%) in the "no prior therapy group" had complete responses (95%
      confidence interval: 3-26%). The major toxicities were moderate leucopenia and
      mucositis. We conclude that FUra plus leucovorin has modest antitumor activity in
      metastatic breast cancer.

PMID- 8141113
TI  - Prognostic factor analysis of central nervous system relapse in adult acute
      lymphoblastic leukemia. A Southeastern Cancer Study Group report.
AB  - A randomized clinical trial in adult ALL has previously shown a benefit for
      central nervous system prophylaxis (intrathecal methotrexate plus cranial
      irradiation) with respect to CNS relapse-free interval, and the long-term follow
      up revealed that about 20% of the patients in this multicenter trial were long
      survivors, probably cured. Questions that were not addressed in the earlier
      reports concern the time to CNS relapse as the initial site of relapse and the
      prognostic factors associated with initial CNS relapse. Further analysis of the
      62 evaluable randomized patients has shown that in every case with CNS relapse,
      time to any relapse and time to CNS relapse as the first event were the same.
      Multivariate analysis showed that, although CNS prophylaxis is a significant
      favorable prognostic factor with respect to CNS relapse over time, race (nonwhite
      is unfavorable) and splenomegaly (unfavorable) are more significant, albeit not
      well explained. Future trials should examine race and splenomegaly as well as
      other clinical and biologic features as potential prognostic factors for CNS
      relapse in adult ALL.

PMID- 8141114
TI  - Acute antiemetic efficacy and safety of dolasetron mesylate, a 5-HT3 antagonist,
      in cancer patients treated with cisplatin. European Dolasetron Study Group.
AB  - Dolasetron mesylate (MDL 73,147EF), a new serotonin receptor (5-HT3) antagonist
      was administered to 164 cancer patients naive or non-naive to chemotherapy, in
      single, rising doses of 10, 20, 30, 40, or 50 mg i.v. 15 minutes prior to an
      infusion of cisplatin. The severity of nausea and number of episodes of emesis
      were recorded during the 24-hour period following cisplatin administration. There
      were significant differences between the dose groups, sex, and naive and non
      naive patients. There were also significant dolasetron dose-dependent differences
      for no emesis (p = .01), less than 3 emetic episodes (p = .01), time-to-onset of
      nausea (p = .04), and time-to-onset of emesis (p = .003). The severity of
      symptoms was greater for females, for patients with previous chemotherapy, and
      with shorter duration of cisplatin infusion. Adjustment for these variables and
      the study center reduced the associations between the dose of dolasetron mesylate
      and the outcome variables. The principal adverse events were headache (11%) and
      diarrhea (6%). Dolasetron mesylate was well tolerated; a single dose of 40 or 50
      mg controlled acute nausea and vomiting induced by highly emetogenic chemotherapy
      in the majority, in particular in chemotherapy-naive and male patients. In
      conclusion, 50 mg and a larger dose merit study in controlled trials with
      stratification for sex and previous chemotherapy.

PMID- 8141115
TI  - Hemophilic pseudotumor: multicenter experience over a 25-year period.
AB  - Pseudotumor is an infrequent manifestation of bleeding diathesis seen in
      hemophiliacs, the management of which is still controversial. To ascertain the
      effectiveness of the main therapies of choice, we have reviewed 1,831 patients
      affected by hemophilias A (1,108) and B (172), von Willebrand's disease (329),
      and other miscellaneous coagulopathies (222) diagnosed between 1965 and 1990 in a
      multicentric, retrospective study. Pseudotumor was proven in 21 patients.
      Replacement therapy was given in 15 cases as the first therapeutic approach, with
      complete success attained in only two, whereas surgery, which was carried out in
      14 patients, completely resolved the process in eight (P = 0.017). Patients over
      40 years of age demonstrated worse prognosis than younger patients (P = 0.02),
      but no other clinical parameters were shown to have influenced the patients'
      evolution. Surgical management was the most effective treatment for pseudotumor,
      although more conservative therapies cannot be overlooked in selected cases.

PMID- 8141116
TI  - Von Willebrand factor availability in platelet concentrates stored for 5 days.
AB  - Von Willebrand factor (vWF) availability was assessed in platelet concentrates
      (PCs). After 5 days of storage, 82 +/- 9% of basal levels of ristocetin cofactor
      activity (vWF:RCo) remained in PCs. vWF antigen (vWF:Ag) increased up to 166 +/-
      38% (P < 0.05) in the same period. Autoradiograph pattern of vW:Ag showed an
      increase in low molecular weight multimers, and fast migrating multimeric forms
      were visualized by crossed immunoelectrophoresis on day 5. Studies carried out in
      platelet free plasma stored as PCs showed similar changes in vWF:RCo but
      increments in vWF:Ag were not detected. These data indicate that PCs maintain
      vWF:RCo levels of clinical value even after 5 days of storage and suggest that
      vWF comes out from platelets to plasma during storage.

PMID- 8141117
TI  - Changes in longevity and causes of death among persons with hemophilia A.
AB  - To examine recent changes in longevity and the causes of death among persons with
      hemophilia A, we evaluated death certificate data for persons who died in the
      United States from 1968 through 1989 and had hemophilia A or congenital Factor
      VIII disorder (ICD code 286.0) listed on the death certificate as one of the
      multiple causes of death. Multiple-cause-of-death mortality data for the United
      States from 1968 to 1989 were examined to compare death rates by year, focusing
      on death rates and causes of death for 1979-1981, 1983-1985, and 1987-1989.
      Gender, age group, race, geographic region, and median age at death of persons
      with hemophilia A and human immunodeficiency virus (HIV)-related disease listed
      as a cause of death were compared with those with hemophilia A without HIV
      related disease. From 1968 through 1989, 2,792 hemophilia A deaths were reported.
      The death rate increased from 0.5 to 1.3 per 1,000,000 persons. From 1979-1981
      through 1987-1989, mortality increased in all age groups above 9 years of age and
      age at death shifted markedly to lower ages. Median age at death decreased from
      57 years in 1979-1981 to 40 years in 1987-1989. The percentage of deaths due to
      hemorrhage or diseases of the circulatory system decreased markedly as the result
      of the increase in deaths associated with HIV infection or infections other than
      HIV infection. Spread of HIV-1 infection in persons with hemophilia A has
      disrupted the reduction in mortality seen with factor replacement therapy,
      implementation of home care, and use of comprehensive hemophilia treatment
      centers. It is hoped that advances in the care of HIV-infected persons will
      improve survival in the hemophilia community.

PMID- 8141118
TI  - Topical thrombin and acquired coagulation factor inhibitors: clinical spectrum
      and laboratory diagnosis.
AB  - Topical bovine thrombin preparations are used extensively in cardiovascular,
      neurosurgical, and otolaryngologic procedures. Patients who are treated with
      these topical thrombin preparations may develop antibodies to bovine coagulation
      factors that may cross-react with the endogenous human clotting proteins. We have
      identified four patients with acquired factor inhibitors following exposure to
      topical thrombin at Duke University Medical Center and summarize these cases in
      addition to 13 patients previously reported in the literature. In most cases, the
      inhibitor developed following a second (or subsequent) exposure to topical
      thrombin. The clinical course was extremely variable, ranging from totally
      asymptomatic to life-threatening hemorrhage. The most consistent laboratory
      abnormality was a prolonged bovine thrombin clotting time, which corrected, at
      least partially, when human thrombin was substituted for bovine thrombin. Some of
      these patients also developed factor V inhibitors with prolonged prothrombin and
      activated partial thromboplastin times. Although these patients have prolonged
      clotting times, they should not be considered "autoanticoagulated," since
      thromboembolic complications can still occur. Therapeutic intervention is largely
      empirical and depends on the clinical manifestations of the individual patient.

PMID- 8141119
TI  - Continuous infusion of monoclonal antibody-purified factor VIII: rational
      approach to serious hemorrhage in patients with allo-/autoantibodies to factor
      VIII.
AB  - Hemorrhage in a patient with factor VIII inhibitor is associated with increased
      morbidity and mortality. Treatment with factor IX complex concentrates or
      recombinant factor VIIa (rVIIa) may not control bleeding and may induce
      thrombosis. In this study, continuous infusion of a monoclonal antibody-purified
      factor VIII [correction of factor VII] concentrate (Monoclate-P) was used
      successfully in two hemophilic patients with factor VIII alloantibodies and one
      nonhemophilic patient with a factor VIII autoantibody. In two patients,
      hemorrhage was life-threatening, and, in one, bleeding did not stop with repeated
      infusions of activated factor IX complex concentrates. The patients' ages ranged
      from 4 to 15 years, and the inhibitor levels from 6 to 300 Bethesda units/ml.
      Clinical hemostasis was excellent, and in vivo recovery of infused factor VIII
      was achieved. When an excess of monoclonal factor VIII was added to the inhibitor
      plasma in vitro, a stable level of residual factor VIII activity was noted after
      an initial rapid loss. This second-order reaction occurs in plasmas of patients
      with type I factor VIII inhibitors. In one patient, we showed that the saturation
      dose of the factor VIII inhibitor predicted in vivo recovery of factor VIII:C.
      These data emphasize the importance of characterizing the kinetic reactions of
      the factor VIII inhibitor. Furthermore, we confirm previous reports that
      continuous infusion of monoclonal factor VIII is a safe and effective treatment
      of patients with factor VIII inhibitors in whom hemorrhage is either life
      threatening or refractory to standard treatment.

PMID- 8141120
TI  - Prevalence of abnormal iron studies in heterozygotes for hereditary
      hemochromatosis: an analysis of 255 heterozygotes.
AB  - Iron studies were compared in 434 patients from 80 hemochromatosis families
      classified as putative homozygotes, heterozygotes, and normal by HLA typing.
      There were 28 of 255 (11%) heterozygotes with an elevated serum ferritin and 22
      of 255 (8.6%) with an elevated transferrin saturation. Serum ferritin (140 +/-
      10.2 micrograms/liter; mean +/- standard error) was greater in heterozygotes than
      in normal subjects (87 +/- 8.5 micrograms/liter; P < .05, Mann Whitney test).
      Transferrin saturation was greater in heterozygotes (38% +/- 0.88%) than in
      normal patients (29% +/- 1.1%; P < .0001). Mean hepatic iron concentration was 54
      +/- 6 mumol/g (n = 17), and the hepatic iron index was < 2 in these patients.
      Most heterozygotes for hemochromatosis have a normal serum ferritin and
      transferrin saturation. Heterozygotes with minor elevations in serum ferritin or
      transferrin saturation do not have significant iron overload as assessed by
      hepatic iron concentration.

PMID- 8141121
TI  - Hypofibrinolysis: a common, major cause of osteonecrosis.
AB  - In 30 patients with osteonecrosis of the hip (12 idiopathic, 18 secondary), we
      assessed the role of hypofibrinolysis mediated by high levels of plasminogen
      activator inhibitor (PAI). We evaluated hypofibrinolysis as a common, potentially
      reversible, pathophysiologic cause of idiopathic osteonecrosis. In all 18
      patients with secondary osteonecrosis, PAI was normal, as was the ability to
      activate fibrinolysis. Nine of the 12 patients with idiopathic osteonecrosis had
      exceptionally high PAI levels and could not normally elevate tissue plasminogen
      activator (tPA-Fx), the major stimulator of fibrinolysis, after 10 min of venous
      occlusion at 100 mm Hg. The group of 12 patients with idiopathic osteonecrosis,
      compared to the 18 with secondary osteonecrosis, had low mean stimulated tPA-Fx
      (1.92 vs. 7.6 IU/ml, P < or = .001) and very high stimulated PAI-Fx (70 vs. 7.6
      U/ml, P < or = .01). Three of the 12 patients with idiopathic osteonecrosis had
      both normal PAI and normal stimulated tPA-Fx. These three patients and 14 of the
      18 with secondary osteonecrosis had high lipoprotein (a) [Lp(a)] (> 20 mg/dl).
      Mean Lp(a) was much higher (60 mg/dl) in the patients with secondary
      osteonecrosis than Lp(a) (16 mg/dl, P < or = .001) in the 12 patients with
      idiopathic osteonecrosis. These findings suggest that hypofibrinolysis mediated
      by high PAI is a common cause of idiopathic osteonecrosis, whereas high Lp(a) may
      play an etiologic role in secondary osteonecrosis. Prospective studies of
      patients with high PAI and/or high Lp(a) should be carried out to assess further
      their apparently causal roles in osteonecrosis.

PMID- 8141122
TI  - Skin manifestation of agnogenic myeloid metaplasia.
AB  - Agnogenic myeloid metaplasia (AMN) with myelofibrosis is a clonal malignancy of
      the hematopoietic stem cell. The disease is characterized by increased
      endothelial cell and fibroblast proliferation, resulting in increased deposition
      of fibronectin, laminin, and collagen in the bone marrow. In advanced disease,
      extramedullary hematopoiesis (EMH) is invariably seen in the spleen and liver.
      The lymph nodes are also frequent sites of EMH, but other organs, especially the
      kidneys, arenals, lungs, pleura, ovaries, gastrointestinal tract, and dura, may
      also be involved. Skin manifestations are rare. They may present in several ways:
      erythematous plaques, nodules, diffuse or papular erythema, ulcers, and bullae.
      Histopathology of these lesions reveals cells from one or more myeloid lineage in
      the dermis, erythroid, or megakaryocytic series alone or in combination. In rare
      cases, all three cell lines are demonstrated.

PMID- 8141123
TI  - Primary amyloidosis associated with a novel heavy-chain fragment (AH
      amyloidosis).
AB  - Primary or AL amyloidosis occurs in patients with monoclonal plasma cell-related
      disorders and is typically associated with the systemic deposition as amyloid
      fibrils of the light-chain portion of the immunoglobulin molecule. Recently, the
      discovery that heavy chains could be involved in amyloid formation led to the
      designation of this type of disease process as AH amyloidosis. We have now
      identified a second example of heavy chain-associated amyloidosis in a patient
      (MAD) who had a serum IgG monoclonal gammopathy and Bence Jones proteinuria. In
      this case, the renal and splenic amyloid deposits consisted solely of the VH-D
      encoded portion of the heavy polypeptide chain, in contrast to the first case,
      where the amyloid contained an immunoglobulin component composed of the entire
      heavy-chain variable and third constant domains. In this respect, the chemical
      composition of the amyloid protein MAD differed not only from that of the first
      reported case of AH amyloidosis but from all other structurally abnormal
      components found in patients with heavy chain-associated disease. The discovery
      that certain forms of heavy chains, as well as light chains, can form amyloid
      provides further information on the chemical basis of amyloidogenicity and the
      diverse nature of this disease.

PMID- 8141124
TI  - Treatment of refractory undifferentiated acute myelogenous leukemia with all
      trans-retinoic acid.
AB  - A patient is described with undifferentiated acute myeloblastic leukemia
      refractory to two courses of daunorubicin and cytosine arabinoside. Because some
      the myeloblasts developed morphologic features of promyelocytes, the patient was
      treated with all-trans-retinoic acid (ATRA) in an attempt to promote maturation.
      Cytogenetic studies and sensitive molecular analysis did not reveal any
      abnormality classically associated with acute promyelocytic leukemia. Serial bone
      marrow biopsies demonstrated myeloid maturation, and the patient uneventfully
      went into a sustained complete remission. A review of the literature confirms
      this to be an apparently hitherto undescribed response to ATRA that may have
      therapeutic implications in similar patients.

PMID- 8141125
TI  - Molecular abnormality of a unique Japanese glucose-6-phosphate dehydrogenase
      variant (G6PD Kobe) with a greatly increased affinity for galactose-6-phosphate.
AB  - Systematic molecular analysis of a Japanese class 1 glucose-6-phosphate
      dehydrogenase (G6PD) variant (G6PD Kobe) cDNA revealed a unique nucleotide
      substitution (1318 C to T) in exon 11, which predicts a substitution of leucine
      for phenylalanine at residue 440. This substitution is located in a region
      surrounding the putative structural NADP-binding domain. The markedly abnormal
      kinetics of glucose-6-phosphate (G6P) of G6PD Kobe suggest the interaction
      between both NADP and G6P binding sites.

PMID- 8141126
TI  - A possible survival advantage in adults with acute leukemia receiving ABO
      identical platelet transfusions.
AB  - In a small cohort of leukemic patients participating in a randomized trial of ABO
      identical vs. ABO-unmatched platelet transfusions, a statistically significant
      decrease in remission duration and increase in mortality were observed in
      patients receiving ABO-unmatched platelet transfusions. This difference was
      unexplained by previously described prognostic factors for remission duration and
      survival. Further study of this association is warranted.

PMID- 8141127
TI  - Acquired ichthyosis as a manifestation of abdominal recurrence of non-Hodgkin's
      lymphoma.

PMID- 8141128
TI  - Cyclosporin therapy for pure red cell aplasia in patients with chronic
      lymphocytic leukemia.

PMID- 8141129
TI  - Serum and red cell ferritin: diagnostic tools and pathophysiologic clues.

PMID- 8141130
TI  - Antiphospholipid antibodies in sickle cell disease.

PMID- 8141132
TI  - Translocation (3;3)(q21;q26)

PMID- 8141131
TI  - Circulating late-stage erythroid progenitors in a patient with agnogenic myeloid
      metaplasia.

PMID- 8141133
TI  - Factor VIIa levels are decreased in patients with hemophilia B.

PMID- 8141134
TI  - Radioimmunometric quantification of surface lactoferrin in blood mononuclear
      cells.
AB  - A radioimmunometric method was developed for the quantification of lactoferrin
      molecules natively bound to blood monocyte and lymphocyte surfaces and the
      estimation of the surface lactoferrin-binding capacity of these cells after their
      incubation with exogenous lactoferrin. Values of surface lactoferrin obtained
      were greatest for monocyte-rich isolates (9,168 +/- 1,713 molecules/cell; n =
      19). The values of monocyte surface lactoferrin for males were similar to those
      of premenopausal females (8,980 +/- 2,378 (n = 8) and 9,427 +/- 2,606
      molecules/cell (n = 11), respectively), but males had slightly lower values of
      monocyte surface lactoferrin binding capacity than did premenopausal females
      (10,447 +/- 2,478 molecules/cell versus 15,958 +/- 3,731 molecules/cell,
      respectively; p > 0.05). Expressed as saturation of the monocyte surface
      lactoferrin binding capacity, values of 97.2% +/- 22.6% for males and 76.6% +/-
      14.3% for females were calculated. Intermediate values of surface lactoferrin
      were found in B-lymphocyte-rich isolates from five patients with B-cell chronic
      lymphocytic leukemia. In T-lymphocyte-rich preparations, there were low levels of
      native lactoferrin expression (154 +/- 63 molecules of lactoferrin/cell; 3
      isolates). The present technique should permit additional quantitative studies of
      mononuclear cell surface lactoferrin to determine the role of lactoferrin surface
      binding and analyses of factors that modulate this binding.

PMID- 8141135
TI  - Case report: use of insulin-like growth factor-I gene expression to distinguish
      between breast and ovarian cancer.
AB  - Autocrine expression of polypeptide growth factors may be important in the growth
      regulation of cancer cells. Different growth factor activities have been
      identified in a variety of tumors. This article describes a case of malignant
      ascites in a patient recently treated for breast cancer. The use of growth factor
      mRNA expression as a factor to differentiate between breast and ovarian origins
      of cancer cells contained in malignant ascites was examined. Expression of
      insulin-like growth factor-I (IGF-I), IGF-II, and transforming growth factor
      alpha mRNA was examined by ribonuclease protection assay. The tumor cells
      expressed IGF-II and transforming growth factor alpha, but not IGF-I mRNA. This
      pattern of growth factor expression is compatible with a breast cancer primary of
      the malignant cells contained in the ascites fluid. Therefore, IGF-I mRNA
      expression may be useful in distinguishing between adenocarcinomas of breast or
      ovarian origins.

PMID- 8141136
TI  - Case report: Castleman disease in association with POEMS.
AB  - Castleman disease, or angiofollicular lymph node hyperplasia, and POEMS
      (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin
      changes), are associated and can lead to a clinical conundrum. The physician
      caring for a patient with Castleman disease should be alert to the development of
      multiple endocrine deficiencies, including primary hypogonadism, diabetes
      mellitus, hypothyroidism, and adrenal insufficiency. Avoidance of treating
      hypothyroidism alone when there is concomitant subclinical adrenal insufficiency
      is important, to avoid precipitating an adrenal crisis. A better outcome may
      result from earlier recognition of the endocrinopathies of this syndrome. This
      article describes a patient with Castleman disease in whom the features of POEMS
      unfolded over the ensuing years.

PMID- 8141137
TI  - Case report: Candida meningitis with an intradural filling defect 1 year after
      candidemia.
AB  - Candida albicans meningitis developed in a 55-year-old diabetic female, 1 year
      after catheter-associated candidemia. It was characterized by a protracted
      course, lack of meningeal signs, and the presence of an intradural filling defect
      within the caudal canal. Complete resolution of this filling defect with
      antifungal therapy implies that it probably represented an inflammatory mass. The
      development of meningitis after self-limiting candidemia and similar intradural
      filling defects have not been reported previously.

PMID- 8141138
TI  - Significance of glutathione in lung disease and implications for therapy.
AB  - Glutathione is a tripeptide that contains an important thiol (sulfhydryl) group
      within the central cysteine amino acid. Glutathione is involved in numerous vital
      processes where the reducing potential of the thiol is used. Several lung
      disorders are believed to be characterized by an increase in alveolar oxidant
      burden, potentially depleting alveolar and lung glutathione. Low glutathione has
      been linked to abnormalities in the lung surfactant system and the interaction
      between glutathione and antiproteases in the epithelial lining fluid of patients.
      Normal levels of intracellular glutathione may exert a critical negative control
      on the elaboration of proinflammatory cytokines. The increase of intracellular
      reactive oxygen species is believed to correlate with the activation of NF-kappa
      B, a transcription activator linked to the elaboration of several cytokines.
      There is now sufficient data to strongly implicate free radical injury in the
      genesis and maintenance of several lung disorders in humans. This information is
      substantial and will help the development of clinical studies examining a variety
      of inflammatory lung disorders.

PMID- 8141139
TI  - Long-term oral anticoagulant therapy: update on indications, therapeutic ranges,
      and monitoring.
AB  - Oral anticoagulant therapy is used extensively in the treatment of deep venous
      thrombosis-pulmonary embolism and prevention of systemic thromboembolism.
      Adoption of the International Normalized Ratio system for the laboratory
      monitoring of therapy has solved the problems encountered with the variable
      sensitivities of the available thromboplastins in North America. Although in
      recent years the recommended intensity of treatment has been reduced for many
      indications, bleeding remains the most common side effect of long-term oral
      anticoagulation therapy. Several drugs interact with warfarin sodium, the most
      commonly used oral anticoagulant drug, and potentiate its effect, thereby
      increasing the risk of bleeding. However, awareness of potential drug
      interactions and careful monitoring to maintain patients within the recommended
      therapeutic ranges can minimize the risk of bleeding and lead to its safe use in
      most patients.

PMID- 8141140
TI  - Cationic lipid enhances in vitro receptor-mediated transfection.
AB  - The efficiency of cell-specific transfection by receptor-mediated uptake is
      improved by the use of cationic lipids. Asialoglycoprotein (AP) was conjugated to
      poly-L-lysine (PL) and complexed with the plasmid pCMVL that contains a
      luciferase reporter gene. The asialoglycoprotein-poly-L-lysine:pCMVL (AP
      PL:pCMVL) complexes then were mixed with the cationic lipid
      dioctadecylamidoglycylspermine (DOGS). This complex was taken up by the
      hepatocyte-like cell line, Hep G2, via the asialoglycoprotein receptor. The
      expression of luciferase in cells transfected with the DOGS/AP-PL: pCMVL
      complexes were significantly increased compared with AP-PL:pCMVL complexes
      without DOGS. The ratio of AP-PL to DOGS is an important determinant for both
      transfection efficiency and for maintaining receptor specificity. Therefore,
      cationic lipids significantly increased the efficiency of asialoglycoprotein
      receptor mediated transfection in the hepatoblastoma cell line, Hep G2. The use
      of cationic lipids with receptor-mediated gene delivery systems could potentially
      increase transfection efficiency yet maintain cell-target specificity.

PMID- 8141141
TI  - Seroreactivity and genomic amplification profile of hepatitis C virus from
      patients with chronic liver disease in India.
AB  - Patients with chronic liver disease were screened initially for antibodies to the
      hepatitis C virus using commercially available assay systems. Positive sera were
      tested for amplification of the 5' noncoding region, and putative structural and
      nonstructural genomic regions of hepatitis C virus by reverse transcription
      polymerase chain reaction. Eight out of 22 patients who were seropositive showed
      presence of viral RNA by amplification from genomic regions. Sera from four
      subjects showed amplification of the 5' noncoding region, a different serum
      showed amplification of the capsid region, and three other sera showed
      amplification of the nonstructural genomic region of the virus. An amplification
      profile of the RNA-positive samples suggests genomic sequence divergence of
      hepatitis C virus circulating among Indian patients.

PMID- 8141142
TI  - Southwestern Internal Medicine Conference: clinical applications of
      transesophageal echocardiography.
AB  - Transesophageal echocardiography has emerged recently as a powerful cardiac
      imaging tool. The strengths and limitations of transesophageal echocardiography
      are reviewed. The clinical use of transesophageal echocardiography in aortic
      dissection, endocarditis, mitral valve disease, prosthetic heart valves, stroke,
      and miscellaneous other conditions is discussed.

PMID- 8141143
TI  - Granulocyte deformability and F-actin content: relationship to diabetes mellitus
      and retinopathy.
AB  - Capillary closure in diabetic retinopathy may be initiated by lumenal occlusion
      by granulocytes. To determine whether subjects with diabetes mellitus have less
      deformable granulocytes than healthy subjects, granulocyte deformability was
      measured by mean entry time into a model capillary system in 16 diabetic
      nondiabetic pairs. Granulocyte F-(filamentous) actin content between groups was
      compared, under basal conditions and after cellular stimulation. The relationship
      of granulocyte deformability to several diabetes-related variables was examined.
      Diabetic granulocytes were only 9% +/- 22% less deformable than normal
      granulocytes (p = 0.16). Deformability was increased in subjects with retinopathy
      and those with the worst glycemic control (r = 0.61, p = 0.026); both findings
      were in the opposite direction from that predicted. Basal and stimulated
      granulocyte F-actin content did not differ between the two groups (p > 0.2 for
      all assays). Although granulocytes may be important in the pathogenesis of
      diabetic retinopathy, granulocyte deformability (measured by mean entry time) and
      F-actin content are not significantly different between healthy patients and
      those with diabetes.

PMID- 8141144
TI  - Real-time ventricular volumes and cardiac function in the working rat heart.
AB  - The measurement of instantaneous left ventricular volumes throughout the cardiac
      cycle in a rat heart beating at rates of 300 to 600 min-1 with a chamber volume
      of only a few tenths of a milliliter is difficult. Combining an x-ray scatter
      detection system with a small x-ray source collimated to scatter low energy x
      rays off a working rat heart, measurements of real-time changes in ventricular
      volumes can be determined. The x-ray scatter signal is proportional to the volume
      and can be calibrated to measure the actual volume. Using this system, changes in
      ventricular function can readily be detected. An example of data obtained from
      increasing preload with a fixed afterload is shown. This technique not only
      distinguishes an increasing stroke volume, but also more rapid early diastolic
      filling and systolic ejection rates with increasing preload. This new x-ray
      scatter technique appears to be a promising way to measure rapidly changing left
      ventricular volumes and function in the working rat heart. This could
      significantly enhance the scientific use of the rat model.

PMID- 8141145
TI  - Effect of meal frequency on serum amino acids and creatinine clearance in young
      men.
AB  - Seven healthy men consumed a liquid formula diet either as 3 meals taken at 0, 4,
      and 8 hours, or as 72 equal portions taken at 10-minute intervals (sipping). Day
      long mean serum amino acids were similar on both treatments. Sipping reduced the
      fall in serum creatinine levels by more than 50% (p < 0.01), and reduced urine
      creatinine output and creatinine clearance by 11% (p < 0.05). These results
      suggest that increased meal frequency warrants investigation as a potentially
      beneficial maneuver in the dietary management of chronic renal failure.

PMID- 8141146
TI  - Hypertension, calcium metabolism, and nephrolithiasis.
AB  - Alterations in calcium metabolism have been detected in both human and rat
      primary hypertension at various levels of the biological organization; in
      particular, an abnormal renal electrolyte handling, leading to chronically
      enhanced urinary calcium excretion, has been demonstrated. In keeping with this
      finding, a significant statistical association between high blood pressure and
      prevalence of nephrolithiasis has been found in three independent population
      based surveys. The first was carried out in the early 1960s in Goteborg, Sweden,
      on 895 50-year-old men, and showed a higher frequency of a positive history of
      nephrolithiasis with increasing blood pressure. The second and third studies were
      performed in Italy, one in the town of Gubbio, with screening of a representative
      sample (n = 3,431; 84%) of the adult population and the other in Pozzuoli,
      Naples, at the Olivetti factory, where 688 male workers (88% of the total male
      workforce) were examined. In both studies, the retrospectively evaluated relative
      risk of nephrolithiasis in hypertensive persons, after controlling for age, was
      significantly higher than in normotensive persons, with hypertension contributing
      by 18% to the overall rate of nephrolithiasis. Hypercalciuria is the most common
      risk factor for nephrolithiasis and, therefore, also a likely pathogenetic link
      between nephrolithiasis and hypertension. Dietary factors play an important
      contributory role in the prevention and treatment of these two widespread
      conditions, and a dietary approach, with particular regard to electrolyte intake,
      is a powerful tool for the prevention of hypertension-related kidney stone
      disease.

PMID- 8141147
TI  - Electrolyte excretion and sodium intake.
AB  - Established essential hypertension is characterized by normal equilibrium between
      the intake and renal excretion of sodium. Urinary sodium excretion is
      interrelated with that of other ions, such as potassium and calcium, and that the
      response of blood pressure to salt ingestion can be conditioned by the
      simultaneous intake of varying levels of those ions. The authors address three
      aspects: the correlations between urinary excretion of sodium and calcium and
      sodium and potassium in a population of untreated essential hypertensive persons,
      the response of blood pressure during the escape induced by exogenous
      mineralocorticoid administration in mild essential hypertension, and the effect
      of intravenous calcium gluconate infusion on sodium excretion and renal function.
      The first part shows that sodium excretion is closely correlated with that of
      other ions in essential hypertension, and the second part shows that, to escape
      from the sodium-retaining effect of a mineralocorticoid, mild hypertensive
      subjects must have increased blood pressure within or near the cutoff point that
      defines salt sensitivity. Of interest, the elevation in blood pressure takes
      place while sympathetic nervous activity is blunted. The third part provides
      evidence to explain one of the mechanisms by which calcium influences renal
      function and enhances renal sodium excretion. The intrarenal effects of low doses
      of calcium are dependent on the renal production of prostaglandins.

PMID- 8141148
TI  - Acid-base abnormalities in hypertension.
AB  - Recent evidence from both salt-sensitive humans and several rat models of
      hypertension indicates an association between metabolic acidosis and genetic
      hypertension. Preliminary findings of increased renal acid excretion suggest that
      the perturbation of acid-base status may be the result of increased metabolic
      acid production. This would be compatible with the previous findings of enhanced
      Na+/H(+)-antiporter activity, reduced intracellular pH levels, and abnormalities
      of carbohydrate and lipid metabolism present in both patients with essential
      hypertension and rat models of genetic hypertension. Further investigation of the
      factors controlling acid-base metabolism in animal models of hypertension and in
      salt-sensitive humans may disclose underlying metabolic abnormalities that could
      account for both the alterations in blood pressure and acid-base status
      associated with genetic hypertension.

PMID- 8141149
TI  - Dietary calcium supplementation, blood pressure, and intestinal calcium
      absorption.
AB  - This study investigated the potential intestinal mechanism in the blood pressure
      lowering effect of dietary calcium supplement. Adult Wistar rats received,
      through a gastrotomy cannula, either 5 or 30 mg elemental calcium.d-1 x 100 g BW
      1 for 10 days. At day 11, mean arterial pressure was measured directly in
      anesthetized animals and calcium absorption determined using an in situ
      measurement technique of calcium absorption. An intestinal loop (duodenum and
      proximal jejunum) was perfused both by the intraluminal and the vascular routes.
      A solution containing 45Ca was perfused intraluminally and the 45Ca appearing in
      the venous effluent was determined to estimate calcium absorption. Oral calcium
      supplementation caused intestinal calcium uptake by the isolated loop to increase
      almost twofold. It also resulted in an 18% increase in mesenteric blood flow. The
      mean arterial pressure was decreased in calcium supplemented rats compared with
      control rats (87 +/- 5 vs. 78 +/- 5 mmHg; p < 0.05). These findings could
      indicate that the passive part of intestinal calcium transport increases in
      response to dietary calcium supplement. This improvement may participate in the
      blood pressure-lowering effect of a high calcium diet.

PMID- 8141150
TI  - Erythrocyte ion transport as indicator of sensitivity to antihypertensive drugs.
AB  - Multiple ion transport defects have been characterized in red blood cell
      membranes from essential hypertensive patients. These seem to be biochemical
      markers of at least three different types of essential hypertension. A first type
      is characterized by low pump, low cotransport fluxes in erythrocytes. These
      hypertensive patients are apparently identical to the salt-sensitive, low-renin
      hypertensive patients, in whom low pump and cotransport seem to result from the
      presence of circulating endogenous ouabain-like and bumetanide-like factors.
      These hypertensive patients are sensitive to diuretic drugs and to vaso-relaxants
      with salidiuretic activity, as expected from a reduction in plasma volume and
      circulating levels of endogenous ion transport inhibitors. A second type of
      essential hypertension is characterized by increased red cell Na+:Li+
      countertransport and [Na+, K+, Cl-] cotransport. These hypertensive patients tend
      to present normal or high plasma renin activity, disorders in lipid metabolism,
      and left ventricular hypertrophy. Hypertensive patients belonging to this group
      seem to be resistant to diuretic drugs but sensitive to vasorelaxants. A third
      type of essential hypertension is characterized by both high membrane sodium leak
      and high [Na+, K+, Cl-] cotransport in erythrocytes. Hypertensive patients in
      this group are resistant to diuretics, angiotensin-converting enzyme (ACE)
      inhibitors, calcium antagonists, and centrally acting drugs.

PMID- 8141151
TI  - Ions, parathyroids, and genetic hypertension.
AB  - Several reports suggested an involvement of parathyroid function in blood
      pressure regulation in animals and humans: hyperparathyroid subjects frequently
      display an elevated systolic blood pressure and young mild hypertensive patients
      show enhanced serum PTH levels. Moreover, removal of parathyroid glands (PTX) in
      young rats attenuates and delays the development of mineralocorticoid and genetic
      hypertension. In addition, in vivo cardiovascular reactivity to norepinephrine in
      PTX rats from both spontaneously the hypertensive rat (SHR) and Lyon hypertensive
      rat (LH) strains is decreased, as is calcium content in aortic and heart
      fragments. Moreover, parathyroid grafts from SHR, stroke-prone SHR (SHR-SP), LH,
      or Milan hypertensive rats (MHS) into previously parathyroidectomized
      normotensive recipient rats have been shown to induce an increase in blood
      pressure. Recently, in essential hypertensive patients and in SHR, a circulating
      hypertensive factor has also been described. Produced by the PTX in SHR, this
      factor is inversely related to the amount of dietary calcium. It appears,
      therefore, that the PTX plays a major role in experimental and probably also in
      human hypertension.

PMID- 8141152
TI  - Stress modulation by electrolytes in salt-sensitive spontaneously hypertensive
      rats.
AB  - Dietary calcium (Ca) has been proposed for the nonpharmacologic treatment of
      hypertension. However, its effect on blood pressure (BP) is debatable, and
      clinical intervention studies have not yet established a clear trend. The authors
      studied literature results on the effect of nutritional Ca on BP in spontaneously
      hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls, using the
      meta-analysis technique. Analysis of the data on inbred animals showed a clear
      effect of dietary Ca on BP: Ca supplementation produced a significant decrease in
      SHR and WKY rats, whereas Ca deprivation induced a significant increase in SHR.
      Furthermore, the hypotensive action of dietary Ca was maximal in salt-sensitive
      SHR (SHR-S), especially when given a high sodium (Na)/high Ca diet. Because the
      SHR-S may be more sensitive to stress than the salt-resistant SHR, the possible
      modulation of stress sensitivity by dietary Na and Ca in SHR-S was examined. High
      Ca regimens prevented salt-sensitive hypertension in SHR-S, with the high Na/high
      Ca diet being most potent in lowering BP. This BP reduction by Ca was paralleled
      by an attenuation of stress sensitivity, as measured by increased body
      temperature during immobilization stress. Therefore, stress sensitivity was
      heightened by dietary Na and diminished by dietary Ca (p < 0.05). It was
      concluded that salt and stress sensitivity in hypertension may be related
      phenotypes that are both modulated in parallel by dietary ions.

PMID- 8141153
TI  - Calcium restriction accelerates salt-induced hypertension in young spontaneously
      hypertensive rats.
AB  - To assess the effect of dietary calcium (Ca) and salt on blood pressure and
      vascular reactivity, 5-week-old male spontaneously hypertensive rats were placed
      on control (1% Ca diet+tap water), high Na (1% NaCl administered in drinking
      fluid), low Ca (0.2% Ca diet), and low Ca+high Na intake for 3 weeks (n = 8-10).
      During the observation period, systolic blood pressure increased in all groups,
      but the increase was markedly enhanced in the low Ca+high Na group. There were no
      significant differences in body weight and serum electrolytes. On high Na
      intakes, urine volume and urinary Na excretion increased and plasma renin
      activity and aldosterone concentration were suppressed, whereas Ca restriction
      did not affect these values. The dose-response curves of mesenteric arterial beds
      for in vitro contraction to norepinephrine (NE) were not affected by dietary
      manipulations. However, the time from maximum contraction to return to baseline
      levels of contractility by 10(-4) M NE was significantly prolonged in the low
      Ca+high Na group. These results indicate that Ca restriction accelerates salt
      induced hypertension in young spontaneously hypertensive rats, and the cellular
      impairment in vascular smooth muscle might, at least in part, participate in the
      enhanced blood pressure elevation under this condition.

PMID- 8141154
TI  - Diabetes modifies cardiovascular reactivity during hypertension.
AB  - Hypertension and diabetes often occur in the same patient, and this observation
      inspired the search for a new common pathogenetic hypothesis. The onset of
      diabetes during hypertension also could modify cardiovascular autonomic arousal.
      To identify a peculiar hemodynamic and psychophysiologic reactivity, a male
      population of mild essential hypertensive (166 +/- 6/102 +/- 8 mm Hg) patients
      (EH) and non-insulin-dependent hypertensive (169 +/- 10/101 +/- 7 mm Hg) diabetic
      subjects (HD) underwent a session of stress tests. Four tests, Mental Arithmetic,
      Incomplete Phrases, Cold Pressor, and Handgrip, were preceded and followed by a
      10-minute recovery period. Functional tests were performed to identify any
      possible cardiac autonomic neuropathy. During the entire session, by means of a
      beat-to-beat noninvasive computerized device, hemodynamic and extracardiovascular
      functions were measured. The findings suggested the presence of a sympathetic
      hyperactivity in both HD and EH. In particular, HD showed a peculiar "tropism"
      for the peripheral vasculature. In these patients, in fact, total vascular
      resistance and peripheral temperature responses were 89.2% and -64.2%,
      respectively, versus 33.7% and -50.6%, which were found in EH. On the other hand,
      the ejection ventricular index was more depressed in HD (-27.9%) than in EH (
      23.8%), although they did not seem to be affected by cardiac autonomic damage.
      The different profiles appear to confirm the increase of functional vascular
      damage in diabetic hypertensive patients, probably because of the insulin
      resistance or obsolete muscular cardiac damage.

PMID- 8141155
TI  - Relationship between erythrocyte cation transport systems and membrane and plasma
      lipids in healthy men.
AB  - The relationship between various transmembrane erythrocyte cationic fluxes and
      erythrocyte membrane and plasma lipids was examined in 53 healthy men. In single
      regression analysis, the erythrocyte Na+,Li(+)-countertransport and Na+,K(+)
      cotransport activity was negatively related to the erythrocyte membrane
      cholesterol, phospholipids, and free fatty acids content. The Na+,K(+)-ATPase
      pump activity as assessed by the ouabain-sensitive Na+ efflux was also inversely
      related to the membrane cholesterol and phospholipids content. In multiple
      regression analysis, the red blood cell Na+,Li(+)-countertransport activity was
      independently and negatively related to membrane cholesterol and free fatty acids
      content. Data show that an elevated level of erythrocyte membrane lipids in
      healthy men is accompanied by a lower Na+,Li(+)-countertransport, Na+,K(+)
      cotransport, and Na+,K(+)-ATPase pump activity.

PMID- 8141156
TI  - Lipids and cardiovascular reactivity changes in hypertensive cigarette smokers:
      enalapril versus nifedipine treatment effects.
AB  - Cigarette smoking has many effects on the cardiovascular system, psyche, and
      serum lipids, which can create a vicious circle that is pejorative to the well
      being of hypertensive patients, even if they are under pharmacologic treatment.
      To investigate the effect of two different antihypertensive agents, nifedipine
      and enalapril, on cardiovascular reactivity and lipoprotein patterns in cigarette
      smokers with hypertension, 92 essential hypertensive (175 +/- 11/103 +/- 8 mm Hg)
      subjects were studied, who had no sign of lipidosis, and subdivided into four
      groups in order of smoking habit and therapy. Over a 30-month follow-up period,
      the percentage changes in blood pressure (BP), heart rate (HR), triglycerides,
      total cholesterol, high density lipoprotein (HDL) and low density lipoprotein
      (LDL) cholesterol were evaluated while the patients underwent a session of
      psychophysiologic tests to assess sympathetic reactivity. The response was
      calculated through the difference in cumulative percentage changes (DC%) in
      systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, muscular
      contraction (EMG), skin conductance (SCL), and peripheral temperature (TP). The
      office BP was reduced significantly in all groups. In the nonsmokers, enalapril
      reduced (p < 0.05) the SCL-, TP-, SBP-, and DBP-DC% reactivity, lowered (p <
      0.05) TR, C-tot, and LDL, and increased (p < 0.05) the HDL. However, nifedipine
      magnified the sympathetic responses and the atherosclerotic lipoproteins and
      decreased (p < 0.05) the HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141157
TI  - 1,25(OH)2 vitamin D3-induced alterations in vascular reactivity in the
      spontaneously hypertensive rat.
AB  - Recent studies showed that 1,25(OH)2 vitamin D3 stimulates calcium uptake in
      vascular smooth muscle cells resulting in increased vascular reactivity. Despite
      reliable effects on vascular tissue, daily injections of 1,25(OH)2 vitamin D3
      have not consistently altered basal blood pressure. In the current study,
      1,25(OH)2 vitamin D3 was examined for vascular reactivity in vitro as well as
      blood pressure reactivity in vivo. 1,25(OH)2 vitamin D3 was either injected as a
      daily subcutaneous dose of 48 ng/kg or placed in an osmotic minipump that was
      implanted subcutaneously and delivered at a rate of 2/ng/kg/hr (48 ng/kg/d).
      Blood pressure reactivity to bolus injections of norepinephrine (NE) and
      angiotensin II (AII) was tested after 1, 6, and 7 days of 1,25(OH)2 vitamin D3
      treatment. On the seventh day, the animals were killed and rings from the aorta
      and mesenteric artery were placed in a muscle bath for measurement of vascular
      reactivity to NE and potassium chloride. Vessels from animals injected with
      1,25(OH)2 vitamin D3 had significantly greater responses to NE (p < 0.001) and
      potassium chloride (p < 0.001) than those from minipump or control animals. There
      was no significant difference in baseline BP across treatment conditions or any
      reliable difference in blood pressure reactivity to NE or AII. The data showed
      that 1,25(OH)2 vitamin D3 can enhance vascular reactivity without altering
      baseline blood pressure or blood pressure reactivity. Moreover, intermittent
      administration of calcitriol may enhance vascular reactivity to norepinephrine
      and potassium chloride to a greater extent than the same dose of calcitriol given
      as a continuous infusion.

PMID- 8141158
TI  - Relationship between acute suppression of plasma renin activity and lymphocyte
      Na+:H+ exchange rate in young patients with borderline hypertension.
AB  - The participation of the cellular sodium content and renin-angiotensin
      aldosterone system in the development of high blood pressure has been frequently
      suggested. To elucidate the role of a mechanism responsible for renal sodium
      reabsorption on the time-course of renin suppression, 16 young borderline
      hypertensive patients were studied by analyzing the relationship between the
      level of baseline activation of lymphocyte Na+:H+ exchange and the degree of
      plasma renin activity (PRA) suppression in response to saline loading. In the
      whole hypertensive population, a significant correlation (R = 0.64; p < 0.01) was
      found between the lymphocyte Na+:H+ exchange activity and the percentage degree
      of PRA suppression induced by saline loading. Urinary sodium excretion was
      enhanced in patients with lesser activation of lymphocyte Na+:H+ exchange and
      greater PRA suppression (3.5 +/- 5 vs. 2.4 +/- .1 umol/min/kg; p < 0.05). These
      findings suggest that a mechanism influencing renal sodium reabsorption as Na+:H+
      exchange could also affect the control of plasma renin activity, and concur with
      the development of salt-sensitive high blood pressure.

PMID- 8141159
TI  - Electrolytes and hypertension: results from recent studies.
AB  - The effects of dietary electrolytes on blood pressure may start as early as the
      prenatal period as there is evidence to suggest that a high maternal calcium,
      magnesium, and potassium intake is reflected in lower infant blood pressure
      levels. One randomized trial in newborn infants suggested that, in this early
      phase, high sodium intake is associated with an increased blood pressure change.
      Such a sodium effect is not present when children grow older, and between 6 and
      16 years a high potassium intake appears to limit the increase in blood pressure.
      Recent observational population studies have shown that the association between
      dietary sodium intake and blood pressure level in adults is less than initially
      reported. In randomized trials, the average fall in blood pressure from moderate
      sodium restriction is small, although benefits may be larger in the elderly. A
      high potassium intake has consistently been shown to reduce blood pressure levels
      in treated and untreated hypertensive subjects, although the overall effects are
      modest. The available data on calcium are difficult to interpret. From
      observational studies an inverse association between dietary calcium intake and
      blood pressure levels has repeatedly been reported. Also, several disturbances in
      calcium metabolism in hypertensive subjects have been demonstrated. Findings in
      randomized trials are less consistent and indicate a marked heterogeneity in
      response.

PMID- 8141160
TI  - Role of potassium in the pathogenesis of hypertension.
AB  - Epidemiologic studies from divergent geographic locations consistently
      demonstrate an inverse correlation between potassium intake and the prevalence of
      hypertension. Studies in experimental animals showed a varied blood pressure
      response to alterations in potassium intake. Spontaneously hypertensive rats and
      rats with renovascular hypertension manifest a hypotensive response to both
      potassium depletion and potassium supplementation. In contrast, potassium
      depletion induced by chronic mineralocorticoid administration is associated with
      an increase in blood pressure. Potassium supplementation in hypertensive subjects
      lowers blood pressure. Amelioration of diuretic-induced hypokalemia with
      potassium supplementation enhances the hypotensive effect of diuretics. Potassium
      depletion induced by dietary potassium restriction elevates blood pressure in
      normotensive and hypertensive subjects maintained on a normal sodium intake.
      Potassium depletion in humans is accompanied by sodium retention and calcium
      depletion. The hypertensive response to potassium depletion and the hypotensive
      response to potassium supplementation do not manifest if sodium intake is kept
      low. Sodium retention, altered response to vasoactive hormones, direct
      vasoconstrictive effects of hypokalemia, and calcium depletion may all contribute
      to blood pressure elevation during potassium depletion.

PMID- 8141161
TI  - Role of anterior hypothalamic angiotensin II in the pathogenesis of salt
      sensitive hypertension in the spontaneously hypertensive rat.
AB  - Selective alterations in noradrenergic mechanisms in the anterior hypothalamic
      area (AHA) of NaCl-sensitive spontaneously hypertensive rats (SHR-S) have been
      demonstrated during dietary NaCl supplementation. To test the hypothesis that
      endogenous angiotensin II (Ang II) in the AHA also plays a role in blood pressure
      regulation and in NaCl sensitive hypertension in the SHR-S, Type 1 Ang II (AT1)
      receptors in the AHA were blocked by local microinjection of losartan, a
      selective nonpeptide AT1 receptor antagonist, and the effects of the intervention
      on blood pressure were observed. Microinjection of losartan into the AHA of
      conscious rats caused a significant dose-related decrease in mean arterial
      pressure in SHR-S but not in Wistar-Kyoto (WKY) rats. To test the hypothesis that
      the depressor response to AHA AT1 receptor blockade is enhanced by high (8%) NaCl
      feeding in SHR-S, losartan was microinjected into the AHA of conscious SHR-S and
      WKY rats that had been fed 1% or 8% NaCl diets for 3 weeks. The magnitude and
      duration of the depressor response to losartan were significantly greater in the
      8% NaCl fed SHR-S than in the 1% NaCl fed rats. These findings, along with the
      observation that Ang II receptor numbers are increased in neurons isolated from
      brain of SHR compared with WKY rats, suggest that endogenous Ang II acting on AT1
      receptors in the AHA participates in the tonic control of blood pressure in SHR-S
      but not in normotensive WKY rats. In addition, it is involved in the pathogenesis
      of NaCl sensitive hypertension in the SHR-S.

PMID- 8141162
TI  - Sodium, large arteries, and diuretic compounds in hypertension.
AB  - Clinical and experimental data have shown that antihypertensive drugs do not
      cause the same change in arterial compliance for an equipotent blood pressure
      reduction. However, there is not clear data on the effect of sodium and diuretics
      on the visco-elastic properties of the hypertensive arterial wall. Cross
      sectional epidemiologic studies suggest that, at any given value of age and blood
      pressure, pulse wave velocity is lower in the presence of decreased sodium
      intake. Longitudinal studies indicate that, in hypertensive subjects, low sodium
      intake is associated with a larger brachial artery diameter than is high sodium
      intake. In hypertension in the elderly and in severe hypertension with end-stage
      renal disease, sodium overload causes a reduction in arterial compliance and
      distensibility unrelated to blood pressure changes. In animal studies, the
      diuretic compounds cycletanine and indapamide were shown to increase systemic and
      carotid compliance independently of blood pressure changes. In contrast, a
      crossover study of hypertensive subjects showed that the diuretic agent
      hydrochlorothiazide did not change arterial compliance and pulse wave velocity,
      whereas the calcium entry blocker, felodipine, improved these parameters.
      Nevertheless, indapamide decreased the pulse pressure on stroke volume ratio, a
      parameter used as a marker of aortic distensibility. Taken together, such studies
      indicate that sodium may act on the arterial wall independently of blood pressure
      changes. The contribution of counter regulatory mechanisms, possibly related to
      the renin-angiotensin and sympathetic nervous systems, might explain the
      differences between the clinical and experimental changes observed with diuretic
      compounds. Of the various antihypertensive agents, diuretics seem to have the
      least effect on the arterial system.

PMID- 8141163
TI  - Sodium kinetics in white and black normotensive subjects: possible relevance to
      salt-sensitive hypertension.
AB  - The hypothesis that sodium (Na) kinetics are not a first order process was
      tested. Twelve normotensive white and 12 normotensive black men were given 10,
      200, and 400 mmol/d Na as the chloride salt for 7 days in random order. All urine
      made was collected. No effect of Na intake on blood pressure was identified in
      either whites or blacks. The half-life (T1/2) with decreasing Na intake to 10
      mmol/d was 1.08 days in whites and 1.65 days in blacks (p = not significant
      [NS]). With increasing Na intake, T1/2 increased in both whites and blacks; at
      the 400 mmol/d intake, the T1/2 for whites was 2.88 days and for blacks was 5.81
      days (p < 0.05). At that intake, whites accumulated 385 +/- 153 mmol compared
      with 909 +/- 153 mmol for blacks (p < 0.05). The data showed that T1/2 increases
      with increasing Na intake and is, therefore, dose-dependent or "zero" order. The
      effect of dose is more prominent in blacks than in whites; blacks accumulate more
      Na with increasing Na intake than whites. These data may have relevance for the
      pathogenesis of salt-sensitive hypertension in blacks.

PMID- 8141164
TI  - Interactions between insulin and sodium homeostasis in essential hypertension.
AB  - It has been proposed, therefore, that hyperinsulinemia may favor the development
      of hypertension through sodium retention, sympathetic nervous system activation,
      and vascular hypertrophy. In insulin-resistant hypertensive subjects, insulin
      infusion during euglycemic clamp promotes a transient sodium retention by
      stimulating proximal tubular Na+ reabsorption, but chronic hypertension usually
      is not associated with extracellular fluid and plasma volume expansion. In
      essential hypertensive subjects, intracellular potassium is decreased and
      intracellular sodium increased, which is consistent with insulin resistance. The
      latter is also associated with high red blood cell Li+/Na+ exchange, and chronic
      insulin treatment in insulin-dependent diabetics induces a slight increase in
      Li+/Na+ CT. This is a functioning mode of the Na+/H+ exchange, and its increase
      may reflect either an increased number of transport units or abnormal kinetic
      properties. Experiments in vitro and in vivo suggested that any change in insulin
      concentration and insulin sensitivity may affect Li+/Na+ and Na+/H+ counter
      transport. High Li+/Na+ and Na+/H+ CT are associated with a significant cardiac
      and vascular remodeling in essential hypertension, insulin-dependent diabetes,
      and familiar hypertrophic cardiomyopathy. Reduced insulin sensitivity is
      associated with salt-sensitive hypertension. Finally, insulin potentiates the
      effects of other agonists (eg, thromboxane A2, angiotensin II) on vascular
      contraction and cell growth. These data indicate that insulin may play a role in
      the pathogenesis of hypertension and its major complications by amplifying the
      effects of sodium, vasoconstrictors, and growth factors.

PMID- 8141165
TI  - Insulin resistance and essential hypertension: mechanisms and clinical
      implications.
AB  - The epidemiologic links among essential hypertension, obesity, and noninsulin
      dependent diabetes mellitus (NIDDM) are well recognized, and it has been proposed
      that these links may reflect an underlying common pathophysiologic link of
      resistance to the action of insulin (insulin resistance). In essential
      hypertension, data suggest the insulin resistance pertains predominantly to
      nonoxidative glucose disposal, especially in skeletal muscle and adipose tissue,
      which contrasts with a more generalized deficit in obesity and NIDDM. A number of
      animal studies of genetic hypertension have confirmed the presence of insulin
      resistance, whereas acquired models of animal hypertension have not. The clinical
      significance of insulin resistance on long-term morbidity in hypertension remains
      unclear; there is limited evidence that insulin resistance may be an independent
      risk factor for subsequent vascular events, but it is more likely that it
      clusters with other better defined risk factors for the vascular complications of
      hypertension. The potential clinical sequelae of insulin resistance and
      hyperinsulinemia and the effect of antihypertensive medication on insulin
      resistance in general are addressed.

PMID- 8141166
TI  - Sodium metabolism, hypertension, and diabetes.
AB  - The hypertension that frequently accompanies diabetes mellitus is characterized
      by abnormalities of sodium (Na) metabolism at all physiologic levels: whole-body,
      renal, and cellular. The most consistently described abnormality is an expansion
      of exchangeable Na, which seems to be closely associated with increased proximal
      renal tubular Na reabsorption and suppression of membrane sodium-potassium ATPase
      activity in circulating cells. Although recent interest has focused almost
      exclusively on the role of hyperinsulinemia in promoting renal Na retention and
      causing expansion of total body Na and Na-dependent hypertension, there is
      evidence that other factors in addition to insulin excess are involved.

PMID- 8141167
TI  - The role of glucose in diabetic hypertension: effects on intracellular cation
      metabolism.
AB  - The clinical association of hypertension, obesity, noninsulin-dependent diabetes
      mellitus (NIDDM), and other cardiovascular risk factors has long been recognized.
      The recent finding that essential hypertension is also an insulin-resistant state
      associated with hyperinsulinemia led some authors to attribute a role in
      mediating this association and in the pathogenesis of hypertension itself to
      insulin. However, evidence also exists independently of insulin per se that
      alterations in glucose metabolism in general, and of hyperglycemia in particular,
      may also contribute to the hypertensive process, especially in the hypertension
      of diabetes. The authors attempted to understand the relationship between glucose
      and insulin metabolism, diabetes, and hypertension from a cellular ionic point of
      view. In vitro it was shown that glucose, in a specific, dose- and time-dependent
      manner, can directly and coordinately alter intracellular ions, increasing
      cytosolic free calcium, while suppressing intracellular free magnesium and pH
      levels. These glucose-induced changes exactly parallel those ionic lesions
      previously observed in vivo in the fasting hyperglycemia of hypertension
      associated with NIDDM. These and other data led to the hypothesis that
      circulating blood glucose, independently of insulin and even at normal levels, is
      a physiologic determinant of cellular ion homeostasis. Furthermore, the cellular
      ionic consequences of hyperglycemia may contribute to the increased risk of
      hypertension and vascular diseases present among subjects with NIDDM, impaired
      glucose tolerance, or both.

PMID- 8141168
TI  - Is the higher incidence of ischemic disease in patients with hypertension and
      diabetes related to intracellular depletion of high energy metabolites?
AB  - To study mechanisms underlying ischemia in hypertension and non-insulin dependent
      diabetes mellitus (NIDDM), 31P-magnetic resonance spectroscopy was used to
      evaluate adenosine triphosphate and 2,3 diphosphoglycerate (2,3 DPG) levels in
      erythrocytes of control (n = 21), hypertensive (n = 22), and NIDDM (n = 10)
      subjects. Compared to adenosine triphosphate levels in controls (2.22 +/- 0.10
      mM), both hypertensive (1.89 +/- 0.10 mM, sig = 0.05 versus normal) and NIDDM
      subjects (1.57 +/- 0.13 mM, sig = 0.05 versus normal) exhibited lower values.
      NIDDM subjects also displayed suppressed levels of 2,3 DPG (6.84 +/- 0.48 mM, sig
      = 0.05 versus normal and EH), compared to hypertensives (8.34 +/- 0.27 mM). These
      data suggest cellular energy metabolism is disrupted in hypertension and NIDDM.
      Both conditions may thereby sensitize tissues to ischemic damage, lower adenosine
      triphosphate levels by decreasing energy reserves, and lower 2,3 DPG levels by
      inhibiting hemoglobin-oxygen dissociation.

PMID- 8141169
TI  - Renal kallikrein-kinin, prostaglandin E2, and dopamine systems in young
      normotensive subjects with a family history of essential hypertension.
AB  - Before dopamine infusion, there were no differences in urinary excretion of
      sodium (UNaV), fractional excretion of sodium (FENa), kinin and kallikrein
      quantity (KALQ), activity (A) or specific activity (Sp) between the young
      normotensive subjects with (FH[+]) and without a family history of essential
      hypertension (FH[-]), whereas urinary dopamine excretion was significantly lower
      and urine volume (UV) and urinary prostaglandin E2 (PGE2) were significantly
      higher in FH(+) subjects than in FH(-) subjects. After infusion of dopamine (3
      micrograms/kg/min for 60 min), the increases in UV, UNaV, FENa, kinin, KALA,
      KALSp, and PGE2 were higher in FH(+) than in FH(-) subjects. From these results,
      it was concluded that (1) the augmented response of urinary kallikrein-kinin and
      PGE2 to infused dopamine in FH(+) subjects could be explained by the hereditary
      suppression of dopamine in the kidneys, and (2) the maintenance of a normal level
      of the basal kallikrein-kinin system and an increase of PGE2 in FH(+) subjects
      may be caused by compensatory mechanisms other than that of renal dopamine.

PMID- 8141170
TI  - The relationship of sodium sensitivity to insulin resistance.
AB  - Substantial epidemiologic evidence has indirectly implicated sodium intake in the
      pathogenesis of hypertension. The concept of sodium-sensitivity as a cause of
      essential hypertension has been addressed by many investigators, yet the
      pathogenesis of this salt-sensitivity remains unclear. Although not well
      appreciated, most studies have shown that regardless of sodium intake or the
      presence or absence of hypertension, sodium-sensitive subjects tend to weigh more
      than sodium-resistant subjects. Insulin-resistance has been postulated to be
      responsible for enhanced sodium retention in obese individuals; therefore,
      insulin-resistance may be critical to the pathogenesis of sodium-sensitivity in
      individuals with essential hypertension. This article summarizes the data
      relating insulin and or insulin-resistance to sodium sensitivity in obesity,
      diabetes, and in non-obese subjects with essential hypertension.

PMID- 8141171
TI  - Tissue renin angiotensin systems: theoretical implications for the development of
      hyperkalemia using angiotensin-converting enzyme inhibitors.
AB  - In patients with renal insufficiency, as the number of functioning nephrons is
      reduced, potassium balance is maintained by an increase in potassium excretion in
      the remaining nephrons. This adaptive response is, in part, mediated by an
      increase in aldosterone production by the adrenal gland. Use of angiotensin
      converting enzyme (ACE) inhibitors in these patients can result in hyperkalemia
      by suppressing aldosterone production by the adrenal gland. Inhibition of
      aldosterone production depends on the degree of inhibition of angiotensin II
      formation in the circulation as well as the degree of inhibition of angiotensin
      II formed locally in the adrenal gland. Recent experimental evidence suggests
      that the latter process may be important for the tonic regulation of aldosterone
      production. Because the various ACE inhibitors exhibit different degrees of ACE
      inhibition at the tissue level, it is reasonable to postulate that angiotensin II
      dependent aldosterone production will be inhibited to a lesser degree by agents
      that have low tissue specificity for the adrenal gland. This feature would be
      most advantageous in treating patients with chronic renal insufficiency and
      congestive heart failure who are at risk for hyperkalemia. Therefore, the ideal
      ACE inhibitor should not suppress aldosterone secretion in such patients.

PMID- 8141172
TI  - Effects of severe and moderate salt restriction on serum lipids in nonobese
      normotensive adults.
AB  - The effects of severe and moderate sodium restriction on blood pressure and serum
      lipids were studied in nonobese normotensive adults. Subjects (n = 163) were
      given a low (20 mmol Na/d) and high (300 mmol Na/d) salt diet for 1 week each in
      random order. Of these subjects, 25 were selected to participate in a second
      study with moderate salt restriction (85 mmol na/d) or "normal" sodium diet (200
      mmol Na/d) given for 4 weeks each in random order. After severe salt restriction,
      19% of the 163 subjects had a significant decrease in blood pressure (salt
      sensitive), 15% showed a significant rise (counter-regulator), and 66% exhibited
      no change (salt-resistant). Severe sodium restriction increased serum total and
      low density lipoprotein (LDL) cholesterol and triglycerides. After correction for
      hematocrit, the changes in blood lipids remained significant in the counter
      regulators only. After moderate salt restriction, serum lipid concentrations and
      blood pressure did not change.

PMID- 8141173
TI  - Na+/H+ exchange and vascular smooth muscle proliferation.
AB  - Abnormal growth of vascular smooth muscle (VSM) is seen in various pathologic
      conditions such as hypertension and atherosclerosis. Many classic
      vasoconstrictors have now been shown to be mitogenic, either by themselves or in
      conjunction with other cofactors, such as insulin. The mitogenic effects of
      vasoconstrictors may be due, in part, to activation of similar second messenger
      pathways, including stimulation of the Na+/H+ antiporter. It has been suggested,
      therefore, that an enhanced proliferation rate may be, in part, the consequence
      of elevated Na+/H+ exchange. This hypothesis is supported by several observations
      of the close association between Na+/H+ exchange activity and DNA synthesis in
      some cell types including fibroblasts and VSM. Stimulation of Na+/H+ exchange may
      play a permissive role in optimal growth by preventing H+ accumulation (a fall in
      intracellular pH [pHi]) due to the increased metabolic activity during cell
      stimulation. Enhancement of Na+/H+ exchange activity increases Na+ influx into
      the cell, and secondarily increases K+ entry through activation of Na+/K+ ATPase
      activity. Although the Na+/H+ antiporter may influence cell proliferation through
      various ionic mechanisms, it is not clear that enhanced proliferation is the
      consequence of overactivity of this antiporter. In VSM, there are also
      differences in the pattern of activation of the Na+/H+ antiporter by hyperplastic
      and hypertrophic agents. Although pHi is increased in response to both acute and
      chronic stimulation by hyperplastic factors, such as platelet-derived growth
      factor, a hypertrophic agonist such as angiotensin II increases pHi acutely but
      lowers it chronically. Likewise, hyperplastic factors increase the Na+/H+
      antiporter (NHE-1) mRNA levels, whereas angiotensin II does not.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141174
TI  - Abnormal regulation of intestinal calbindin (CaBP9k) and calmodulin in the
      spontaneously hypertensive rat.
AB  - This review focuses particularly on abnormalities of Ca-binding proteins in
      transporting epithelia, which have been observed in various models of
      experimental hypertension. The enterocyte content of integral membrane Ca(2+)
      binding protein (IMCAL) and calbindin-9k and the renal tubular calbindin-28k
      content have been shown to be decreased in the spontaneously hypertensive rat
      (SHR), compared with normotensive control rats (WKY). Similarly, calmodulin
      content was decreased in several tissues including the intestine; however,
      calmodulin activity was increased. In recent studies, the authors examined the
      response of intestinal calbindin-9k, calbindin-9k mRNA, and calmodulin contents
      to low-Ca and high-Ca diets in these two rat strains. It was shown that the SHR,
      unlike the WKY, was unable to augment intestinal calbindin-9k and calbindin-9k
      mRNA levels in response to a low-Ca diet of short duration. On the other hand, a
      high-Ca diet led to a similar decrease in calbindin-9k content in both SHR and
      WKY rats. Enterocyte calmodulin content was also diminished in the WKY, but not
      the SHR, fed such a high-Ca diet. Therefore, abnormal Ca-binding proteins could
      play a role in the disturbed Ca metabolism of arterial hypertension.

PMID- 8141175
TI  - More than tenfold increase of arsenic in serum and packed cells of chronic
      hemodialysis patients.
AB  - Arsenic concentrations were determined in serum and packed cells of 7 chronic
      hemodialysis patients, in fresh dialysate and in a heparin solution. The
      analytical technique was radiochemical neutron activation analysis. The accuracy
      of the method was tested by the analysis of As in certified reference materials.
      Patients showed elevated serum and packed cell arsenic concentrations compared
      with controls (serum, range: 2.3-79.8 ng As/ml, median: 11.5 ng As/ml; versus
      range: 0.132-4.783 ng As/ml, median: 0.38 ng As/ml; packed cells, range: 2.1-68.4
      ng As/g, median: 9.5 ng As/g; versus range: 0.51-14.44 ng As/g, median: 3.17 ng
      As/g). Arsenic concentrations remained unaltered, before versus after a single
      hemodialysis treatment. The arsenic contents of serum and packed cells were
      significantly correlated (n = 7, r = 0.96, p < 0.05). No arsenic could be
      detected in the heparin solution or in the dialysate.

PMID- 8141176
TI  - Retropharyngeal infection with Staphylococcus aureus in a haemodialysis patient.
AB  - The case of a 55-year-old female Asian haemodialysis patient is described. She
      developed a septicaemic illness and retropharyngeal soft-tissue infection
      secondary to Staphylococcus aureus infection.

PMID- 8141177
TI  - Prospective randomized study of azathioprine versus cyclosporin in live-donor
      kidney transplantation.
AB  - A total of 112 recipients of haploidentical live-related donor kidney transplants
      were assigned randomly prior to transplantation to two groups of
      immunosuppressive treatment. The first group (54 patients) received the
      conventional immunotherapy of azathioprine (AZA) and prednisolone (P; AZA-P
      group). In the second group, 58 patients were given cyclosporin (Cs) and P (Cs-P
      group). All patients had previous third-party blood transfusions. The follow-up
      period ranged from 3 to 6 years (mean 50 +/- 8 months) during which 13 patients
      (24%) in the AZA-P group and 6 (10%) in the Cs-P group were switched to the
      alternate immunotherapy (p > 0.05). Analysis of patient and graft survival along
      the follow-up period did not disclose significant differences between patients of
      the two groups. While the overall frequency of acute rejection episodes was not
      significantly different between the two treatment groups, the number of patients
      who had 2 or more rejection episodes was higher in the AZA-P group (p < 0.04).
      The mean serum creatinine levels were significantly higher in the Cs-P group than
      corresponding levels in the AZA-P group at 1, 12 and 24 months after
      transplantation. We have concluded that at least 75% of the haploidentical human
      lymphocyte antigen mismatched live-related donor renal transplants can be
      maintained on AZA-P immunotherapy with a comparable degree of success to those
      treated with Cs-P. However, in at least 15% of patients with conventional
      immunotherapy, Cs could reverse ongoing rejections, and therefore, it can be
      considered as a rescue treatment in AZA-treated patients with steroid-resistant
      or ongoing rejections.

PMID- 8141178
TI  - Urinary N-acetyl-glucosaminidase excretion and environmental lead exposure. Green
      Cross Health Service Association Study Group.
AB  - To understand the relationship between chronic low-level lead exposure and renal
      function, residents living nearby a lead battery factory for more than 10 years
      were selected and entered in this cross-section study. The residents living in
      the 1st village, within 500 m from the factory, were grouped in group 1; those in
      the 2nd village, within 1,000-1,500 m, in group 2, and those in the 3rd village,
      far from any lead-contaminated sources, in group 3. Twenty-four-hour urinary N
      acetyl-glucosaminidase (NAG) was detected as early indicator of renal damage, and
      an ethylenediamine-tetraacetic acid mobilization test was performed to estimate
      total body lead burden of lead-exposed persons. Blood lead level (BLL) showed a
      significant difference among the three study groups. The further the distance
      between the group and the factory, the higher BLL. The results showed a
      significant high prevalence of abnormal urine NAG excretion in the chronic lead
      exposed group, although BLL and body lead burden of these persons were within the
      'normal' range. A significant correlation between body lead burden less than 200
      micrograms and 24-hour urine NAG excretion and a dose-response relationship
      between them were found. These observations suggested that lead was the possible
      cause of abnormal renal tubular function in persons with chronic low-level lead
      exposure, but this effect became blunt when body lead burden was more than 200
      micrograms. The possible explanation may be that high body lead burden from long
      term exposure will deplete the kidney of NAG or render it insensitive to the
      effects of lead exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141179
TI  - Mathematical formulation to help identify the patient at risk of ischemic tissue
      necrosis--a potentially lethal complication of chronic renal failure.
AB  - Ischemic tissue necrosis (ITN) has been described as a complication of
      hyperparathyroidism (HPT) in patients with end-stage renal disease (ESRD) and is
      associated with a mortality rate of up to 80%. Early recognition of ITN is
      important but difficult. Optimal treatment is controversial. Based on an analysis
      of the English literature and a recent clinical experience, a mathematical
      expression to aid in the identification of high-risk patients (2 x [CaPO(4) - 5]
      x alkaline phosphatase x PTH ratio) was developed. The values for this expression
      were calculated in 3 recently reported cases and our case (n = 4). The values
      were compared with those of a group of 54 hyperparathyroid chronic hemodialysis
      patients (controls); the mean values were significantly different (p < 0.001).
      The expression, consisting of 4 easily measured laboratory values, appears to
      differentiate patients with this complication of ITN from patients with only
      severe HPT. Ten new additional cases were evaluated using the equation; the
      sensitivity of the equation was 80% and the specificity 92%, positive predictive
      value was 66% and the negative predictive value 96%. Long-term validation of this
      equation is required but it appears to be discriminatory and, thus, promising,
      given the potentially lethal consequences of ITN.

PMID- 8141180
TI  - Limitations of kinetic models as predictors of nutritional and dialysis adequacy
      in continuous ambulatory peritoneal dialysis patients.
AB  - Nutrition has been shown to predict clinical outcome in continuous ambulatory
      peritoneal dialysis (CAPD) patients. However, despite the positive relationship
      between KT/V (urea) and the normalised protein catabolic rate, the ability of
      urea kinetic modelling to predict clinical outcome or nutrition remains
      inconclusive. We have evaluated the relationship between nutrition and achieved
      dialysis in a cross-sectional study of 147 stable CAPD patients on dialysis for a
      mean period of 22 months. Protein-energy malnutrition was present in 22-32% of
      the study population. 39 and 41% of the population failed to achieve suggested
      adequacy targets of 50 liters/week for total creatinine clearance and a weekly
      KT/V (urea) of 1.7, respectively. Severely malnourished patients had
      significantly greater normalised clearance and adequacy values than well
      nourished patients. Intrinsic actual peritoneal clearance bore no relation to
      patient size. The subsequent normalisation of this value by a component of
      patient mass results in a mathematical bias against well-nourished or obese
      patients. This may explain the failure of such adequacy values to reflect outcome
      and argues against accepting such values as measures of dialysis well-being.

PMID- 8141181
TI  - Erythrocyte vitamins B1, B2 and B6 and erythropoietin.
AB  - The influence of recombinant human erythropoietin (r-HuEPO) on erythrocyte
      vitamins B1, B2 and B6 was investigated in regular dialysis treatment (RDT)
      patients during a long-term 9-month study. Twenty-six RDT patients were divided
      into two groups. Group A was without r-HuEPO treatment while group B was treated
      by subcutaneous injection of r-HuEPO. The total maintenance weekly dose of r
      HuEPO was 50-100 U/kg. Group A of patients was supplemented with oral pyridoxine
      5 mg/day during the period of 9 months; group B was supplemented with oral
      pyridoxine 5 mg/day for the first 6 months and with 20 mg/day during the
      following 3 months. At the end of the study, significant increase in erythrocyte
      vitamin B2 and significant decrease in erythrocyte vitamin B6 were found.
      Supplementation with 20 mg/day of pyridoxine led to a significant increase in
      vitamin B6 and at the end of the 9 months, the values of vitamin B6 were within
      the normal range. These results provide indirect evidence that erythrocyte
      vitamin B6 is consumed by the hemoglobin synthesis during r-HuEPO treatment in
      RDT patients.

PMID- 8141182
TI  - Normalization of enhanced neutrophil cytosolic free calcium of hemodialysis
      patients by 1,25-dihydroxyvitamin D3 or calcium channel blocker.
AB  - Patients undergoing regular hemodialysis treatment display elevated intracellular
      free calcium and impaired glucose uptake in polymorphonuclear leukocytes (PMNLs)
      in the presence of enhanced serum parathyroid hormone (PTH) levels. Normalization
      of intracellular calcium can be achieved by different therapeutic interventions
      acting by different mechanisms. Effective oral 1,25-dihydroxyvitamin D3 therapy
      (0.5-1.0 microgram/day) normalizes PMNL cytosolic calcium via suppression of PTH
      levels. Hemodialysis patients treated orally with the calcium channel blocker
      nitrendipine (20-40 mg/day) normalizes calcium without affecting serum PTH
      levels. Both therapeutic interventions improved glucose uptake and displayed no
      synergistic effect.

PMID- 8141183
TI  - Role of bradykinin in anaphylactoid reactions during hemodialysis with AN69
      dialyzers.
AB  - In vitro experiments have related anaphylactoid reactions in patients treated
      with angiotensin-converting enzyme (ACE) inhibitors during dialysis with AN69
      membranes to excessive bradykinin generation using this negatively charged
      dialysis membrane. In the present clinical trial plasma bradykinin levels were
      followed during the early phase of dialysis in 10 patients, not being treated
      with ACE inhibitors, using AN69, cuprophane, and polysulfone membranes.
      Bradykinin was measured after extraction by radioimmunoassay. During this study
      one episode of anaphylaxis occurred during dialysis with the AN69 membrane. Blood
      samples were collected during the first 5 min of the adverse reaction and showed
      a more than 100-fold increase in the venous effluent of the AN69 dialyzer
      (baseline 40 +/- 3 vs. 4,900 +/- 130 fmol/ml after 5 min). Even though none of
      the patients received ACE inhibitors, there were 4 more asymptomatic individuals
      who displayed a more than two-fold increase in their plasma bradykinin
      concentrations in the venous effluent of the AN69 dialyzer. When these patients
      were treated either with cuprophane or with polysulfone dialyzers, no significant
      bradykinin formation was detected, nor were there any adverse events. Taken
      together, these findings show that anaphylactoid reactions with the AN69 membrane
      are due to excessive bradykinin generation which even may occur in the absence of
      ACE inhibitors.

PMID- 8141185
TI  - Renal parenchymal malacoplakia and megalocytic interstitial nephritis: clinical
      and histological features. Report of two cases and review of the literature.
AB  - We report 2 cases of acute renal failure caused by rare and closely related
      inflammatory conditions, i.e. renal parenchymal malacoplakia and megalocytic
      interstitial nephritis. We have discussed the clinical presentation, natural
      progression of the disease, the short- and longterm prognosis of the kidney, the
      histological appearances, the radiological features and the medical therapy
      together with a review of the literature.

PMID- 8141184
TI  - Effect of dietary cholesterol on rat glomerular cholesterol esterase.
AB  - The accumulation of tissue cholesterol and cholesteryl esters is commonly seen
      during the development of both atherosclerosis and glomerulosclerosis. The
      intracellular cholesterol content is regulated, in part, by the hydrolysis of
      cholesteryl esters to cholesterol, a reaction catalyzed by cholesterol esterase.
      Decreased cholesterol esterase has been linked to cholesteryl ester accumulation
      in vascular cells and has been postulated to be an important factor in the
      progression of atherosclerosis and, possibly, glomerulosclerosis. In order to
      determine whether cholesterol esterase regulates glomerular cholesterol
      accumulation, the effect of cholesterol feeding on the cholesterol content and
      the activity of cholesterol esterase was examined in rat glomeruli. Cholesterol
      esterase was measured using a cholesteryl[1-14C]oleate-lecithin liposome
      substrate. Total and free glomerular cholesterol was measured
      spectrofluorometrically. Feeding rats 4% cholesterol for 2 months decreased total
      glomerular (acid plus neutral) cholesterol esterase activity when compared to
      glomeruli from similar rats fed a normal chow (1.8 +/- 0.1 versus 1.48 +/- 0.2
      nmol/mg protein/h, p < 0.05). Total, free and esterified cholesterol
      concentrations were higher in glomeruli from cholesterol-fed rats than from
      controls, consistent with decreased cholesterol esterase activity. Thus,
      glomerular cholesterol accumulation appears to be regulated by cholesterol
      esterase. This finding is similar to that in other vascular tissues which have
      been investigated and which are prone to accumulate cholesterol during the
      development of atherosclerosis.

PMID- 8141186
TI  - Renal cholesterol embolic disease. Case report and review of the literature.
AB  - Renal cholesterol embolization is a rare disease occurring usually in elderly men
      who had undergone an angiographic procedure or vascular surgery. We report a man
      who developed systemic cholesterol embolic disease and acute renal failure after
      coronary angiography. A review of the English literature for renal cholesterol
      embolic disease revealed a high incidence of eosinophilia (71%). Livedo
      reticularis and digital infarcts occurred in more than 30% of patients. Forty
      percent of patients required dialysis for acute renal failure of whom only one
      fifth recovered sufficient renal function to stop dialysis. The overall mortality
      was high at 64%. Skin, muscle and kidney biopsies remain the main tools for
      diagnosis.

PMID- 8141187
TI  - Antiglomerular basement membrane antibody-mediated nephritis with normal
      pulmonary and renal function. A case report and review of the literature.
AB  - Antiglomerular basement membrane (anti-GBM) antibody-mediated disease is usually
      characterized by a rapidly progressive glomerulonephritis with or without
      pulmonary hemorrhage. We report a case of anti-GBM-mediated nephritis that
      presented with hematuria and proteinuria. There was no evidence of renal
      insufficiency or pulmonary hemorrhage. Clinicians should be aware of this rare
      presentation of anti-GBM-mediated nephritis.

PMID- 8141188
TI  - Effects on the menstrual cycle of in utero exposure to diethylstilbestrol.
AB  - OBJECTIVES: The purpose of this study was to determine the effects of in utero
      exposure to diethylstilbestrol on the menstrual cycle. STUDY DESIGN: This was a
      prospective cohort study of 198 diethylstilbestrol-exposed women and 162
      unexposed controls, recruited from women whose mothers participated in a
      randomized trial of diethylstilbestrol in pregnancy at the Chicago Lying-In
      Hospital from 1950 to 1952. Women with severe menstrual abnormality were excluded
      from the study. RESULTS: Diethylstilbestrol exposure was associated with a
      statistically significantly decreased duration of menstrual bleeding of
      approximately one half day and a lower average daily bleeding score (self
      reported). We found no evidence for effects of diethylstilbestrol exposure on
      cycle length or variability of cycle length. Exposure was not related to symptoms
      of dysmenorrhea. CONCLUSIONS: The decreased duration and amount of menstrual
      bleeding among diethylstilbestrol-exposed women could be due to direct effects on
      the uterus. The lack of an effect on cycle length and variability appears to
      indicate that endocrine function is not grossly disturbed in those women studied.

PMID- 8141189
TI  - Pedunculated uterine fibroid simulating an incarcerated inguinal hernia in
      pregnancy.
AB  - A bulging 5 x 5 cm tender mass appearing intermittently in the left groin in
      association with vigorous physical activity between 20 and 24 weeks' gestation
      was thought clinically and ultrasonographically to represent an inguinal hernia.
      Surgery after acute continuous pain and concern for incarceration revealed a
      nonherniated pedunculated uterine fibroid.

PMID- 8141190
TI  - Changes in hemorheology with fetal intravascular transfusion.
AB  - OBJECTIVE: Our aim was to determine the changes in fetal hemorheologic parameters
      caused by fetal intravascular transfusion for alloimmune anemia. STUDY DESIGN:
      Fetal blood samples were collected before and after 95 fetal transfusions in 31
      women. Fetal hematocrit, whole-blood viscosity at a variety of shear rates,
      plasma viscosity, fetal fibrinogen, and fetal plasma proteins were measured.
      RESULTS: Fetal whole-blood viscosity increased, sometimes massively, with
      transfusion. The rise in viscosity was principally dependent on the rise in
      hematocrit, with a linear rise in hematocrit producing a linear rise in the
      logarithm of whole-blood viscosity, but was also affected by the amount of adult
      plasma proteins present in the donor blood. CONCLUSIONS: Rises in fetal whole
      blood viscosity during transfusion can be minimized by using donor blood that has
      been serum depleted to a high hematocrit (> 90%) and by restricting the end
      hematocrit to 50% to 55%.

PMID- 8141191
TI  - Acute vaginal bleeding in women undergoing liver transplantation.
AB  - OBJECTIVES: Our aim was to define the nature of acute vaginal bleeding problems
      in women undergoing liver transplantation and to determine the efficacy of
      treatments given. STUDY DESIGN: We performed a retrospective chart review of 24
      patients undergoing liver transplantation in whom consultation was requested for
      vaginal bleeding. RESULTS: Twenty-four liver transplant patients were seen for
      evaluation of acute vaginal bleeding. Two patients were seen before
      transplantation, and 16 women were evaluated for bleeding after transplantation
      (8 within the first 15 postoperative days). In the other eight women abnormal
      uterine bleeding developed between 2 months and 5 years after transplantation.
      Five of these women had compromised liver function. In six other women vaginal
      bleeding originated from extrauterine sources. Six of seven endometrial biopsy
      specimens revealed proliferative endometrium, and the other showed adenomatous
      hyperplasia. Three of four patients had a response to progestational agents,
      bleeding stopped spontaneously in three patients, two required hysterectomy, and
      three died of other causes. The other five patients were not seen again by us
      before or after discharge from the hospital. CONCLUSIONS: Medical or surgical
      therapy can effectively control acute vaginal bleeding in liver transplant
      patients.

PMID- 8141192
TI  - Successful management of viable cervical pregnancy by local injection of
      methotrexate guided by transvaginal ultrasonography.
AB  - We evaluated the feasibility of transvaginal methotrexate injection of viable
      cervical pregnancies to avoid complications of the "classic" surgical procedures
      in use and to preserve future fertility. Five viable cervical pregnancies, at 6
      to 8 weeks, were treated. In three patients a spring-loaded automated puncture
      device and in two a manually operated simple needle guide mated to and guided by
      a transvaginal ultrasonography probe were used with 21-gauge needles. The
      puncture and injection treatment was successful and without complications in all
      five cases presented. This procedure may become a useful alternative to other,
      more radical or complex surgical approaches.

PMID- 8141193
TI  - Is the risk of perinatal transmission of human immunodeficiency virus increased
      by the intrapartum use of spiral electrodes or fetal scalp pH sampling?
AB  - OBJECTIVE: Our aim was to determine whether the intrapartum use of fetal scalp
      electrodes or fetal scalp pH sampling increases the rate of perinatal
      transmission of human immunodeficiency virus. STUDY DESIGN: The rate of perinatal
      transmission of human immunodeficiency virus in 31 monitored pregnancies was
      determined, and those pregnancies were compared with a control group of 117
      pregnancies. RESULTS: The monitored group was comparable to the control group
      with respect to maternal age, race, human immunodeficiency virus risk behavior,
      CD4+ cell count, p24 antigen status, and stage of human immunodeficiency virus
      disease. The mean gestational age at delivery and the mean birth weight were
      similar in the monitored group and the control group. The perinatal transmission
      rate for the monitored group (29.0%) was not statistically different from that of
      the control group (25.6%). CONCLUSIONS: If confirmed by larger studies, our
      findings suggest that the intrapartum use of fetal scalp electrodes or fetal
      scalp pH sampling does not appear to increase the perinatal transmission of human
      immunodeficiency virus.

PMID- 8141194
TI  - Prematurity prevention programs: an analysis of successes and failures.
AB  - OBJECTIVE: Our purpose was to assess the long-term results of established
      prematurity prevention programs. STUDY DESIGN: A population cohort of pregnant
      women from two major urban health care organizations were examined. Rates and
      cost-benefit analysis of prematurity and patient, system, or physician failures
      were analyzed. During 1990 1143 pregnant women were prospectively reviewed.
      RESULTS: A total of 11.8% of the mothers were high risk and responsible for 108
      (50.2%) of the preterm deliveries. The preterm birth rate of all enrollees was
      4.6%. One percent of the preterm neonates required level III care for
      complications. The average charge for a 35 week infant was 18 times, and a 36
      week infant was five times more costly than a term infant. Patient, physician,
      and health care system failures occurred at different rates. CONCLUSIONS: This
      preterm prevention program resulted in low preterm birth rates. Potentially
      preventable preterm births most often occurred as a result of patient and
      physician failures.

PMID- 8141195
TI  - Unusual endovaginal ultrasonography and magnetic resonance imaging of placental
      site trophoblastic tumor.
AB  - Previous reports of ultrasonographic and magnetic resonance imaging of placental
      site trophoblastic tumor have described a cystic appearance of this rare disease.
      We present the first case in which endovaginal ultrasonography and magnetic
      resonance imaging revealed a solid intramural mass.

PMID- 8141196
TI  - Prognostic indicators in the prenatal diagnosis of agenesis of corpus callosum.
AB  - OBJECTIVE: Our aim was to determine the accuracy of ultrasonography in the
      prenatal diagnosis of agenesis of the corpus callosum and to establish whether
      ultrasonography can provide prognostic indicators in cases of agenesis of the
      corpus callosum. STUDY DESIGN: Prospective ultrasonographic study of the corpus
      callosum in all cases during an 8-year period in which fetal cerebral
      ventriculomegaly was detected. RESULTS: A total of 14 cases of agenesis of the
      corpus callosum are reported. In seven cases agencies of the corpus callosum was
      an isolated finding, and in seven cases it was associated with other
      abnormalities. Six cases involved mendelian syndromes (3 Lissencephaly syndrome,
      2 Aicardi syndrome, and 1 Andermann syndrome), and one case was associated with
      trisomy 13. In 5 of 14 fetuses, all male, agenesis of the corpus callosum was an
      isolated benign finding. The corpus callosum could never be visualized before
      midgestation, but diagnosis of agenesis of the corpus callosum was very accurate
      after 20 weeks. CONCLUSION: Prenatal ultrasonographic findings suggestive of
      agenesis of the corpus callosum should be followed by a careful search for
      associated anomalies that may indicate genetic syndromes. Isolated agenesis of
      the corpus callosum is often an isolated, benign finding, particularly in male
      fetuses. In families at risk for mendelian syndromes associated with agenesis of
      the corpus callosum, lack of visualization of this structure is suggestive of the
      diagnosis.

PMID- 8141197
TI  - Bacterial vaginosis: efficacy and safety of intravaginal metronidazole treatment.
AB  - OBJECTIVE: We evaluated the effectiveness and safety of intravaginal
      metronidazole in the treatment of bacterial vaginosis. Demographic data, Gram
      stain score, and individual clinical diagnostic criteria for bacterial vaginosis
      were evaluated for association with therapeutic outcome. METHODS: According to
      accepted diagnostic criteria and blinded Gram stain scoring for quality control,
      a multicenter, prospective, double-blinded trial of patients randomized to either
      0.75% metronidazole gel 5 gm twice daily for 5 days or placebo was undertaken.
      Therapeutic response after completion of treatment was evaluated by examination
      at 4 to 16 days and again at 28 to 32 days for patients initially cured. RESULTS:
      After metronidazole treatment, 38 (78%) of 49 patients were cured initially,
      compared with 11 (27%) of 41 placebo recipients (p < 0.001). One month after
      treatment 31 (91%) of 34 in the group initially cured by metronidazole remained
      cured. Side effects were uncommon and mild. Significant intercenter differences
      were noted for vaginal discharge assessment but not for other diagnostic
      criteria. Among patients cured initially with metronidazole, mean Gram stain
      score was 0.58 among those in whom cure was maintained versus 2.33 for those in
      whom recurrent bacterial vaginosis developed 1 month after treatment (p = 0.03).
      Curative metronidazole treatment was found initially in 4 (100%) of 4 patients
      with sperm present on gram stain compared with 34 (76%) of 45 with sperm absent
      (p = 0.56) and in 6 (100%) of 6 and 25 (89%) of 28, respectively, at the final
      visit (p = 1.0). CONCLUSIONS: Intravaginal metronidazole is effective, safe, well
      tolerated, durable therapy for bacterial vaginosis. Characterization of vaginal
      discharge appears to be the most variable among the diagnostic criteria for
      bacterial vaginosis. Gram stain score may be able to identify patients cured
      early after therapy who are at risk for later recurrence. Exposure to semen does
      not appear to affect efficacy of intravaginal metronidazole.

PMID- 8141198
TI  - Monitored outpatient management of mild gestational hypertension remote from
      term.
AB  - OBJECTIVE: Our purpose was to test the hypothesis that monitored outpatient
      management of mild gestational hypertension remote from term reduces maternal
      hospitalization without adversely affecting maternal and perinatal outcome. STUDY
      DESIGN: Five hundred ninety-two patients at 24 to 36 weeks' gestation with mild
      gestational hypertension were monitored on an outpatient basis with four times
      daily automated blood pressure measurement and daily assessment of weight,
      proteinuria, and fetal movement. Maternal and perinatal outcomes were compared
      with previously published results from inpatient management of mild gestational
      hypertension. RESULTS: The mean gestational age at enrollment was 32.5 +/- 3.2
      weeks with a mean gestational age at delivery of 36.7 +/- 3.6 weeks. The mean
      pregnancy prolongation was 27.4 +/- 3.3 days, which is similar to previously
      reported inpatient studies. The mean antepartum hospitalization for all patients
      during management was only 1.7 days. Three pregnancies were complicated by
      abruptio placentae, six by the syndrome of hemolysis, elevated liver enzymes, and
      low platelet count, and none by eclampsia. The mean birth weight was 2757 +/- 555
      gm, with a birth weight of > or = 2000 gm achieved in 84% of managed patients.
      Eighty-seven percent of infants required a newborn hospitalization of < or = 7
      days. Fifty-four percent of patients with significant proteinuria at enrollment
      were delivered at < 37.0 weeks' gestation, whereas only 29% of patients without
      proteinuria were delivered prematurely. The corrected perinatal mortality rate
      was 3.4 in 1000 total births. CONCLUSION: Properly monitored outpatient
      management of mild gestational hypertension remote from term reduces the number
      of days of maternal hospitalization with similar maternal and perinatal outcome
      compared with previously published results from inpatient management.

PMID- 8141199
TI  - Spatiotemporal properties of the fetal magnetocardiogram.
AB  - OBJECTIVE: Our purpose was to investigate the spatiotemporal properties of the
      fetal magnetocardiogram. STUDY DESIGN: Fetal magnetocardiogram maps were measured
      for the first time in 20 subjects from 22 to 39 weeks' gestation. Waveform and
      topographic maps were used to display the data. RESULTS: The maps showed
      spatiotemporal properties consistent with simple volume conductor theory:
      topography was closely related to the presentation of the fetus, Q-wave sources
      were dipolar and localized, the magnetic heart vector rotated extensively during
      the QRS complex, and close correspondence was observed between fetal and neonatal
      maps. Ventricular depolarization and events in the cardiac cycle could be
      visualized in considerable detail by means of a time series of topographic maps.
      CONCLUSION: Fetal magnetocardiogram shows excellent spatiotemporal properties and
      is well suited for in utero studies of fetal heart activity.

PMID- 8141200
TI  - Resident research projects: frequency of presentation and publication in a
      national forum.
AB  - OBJECTIVE: Our aim was to determine the fate of mandatory resident research
      projects with regard to subsequent presentation and publication. STUDY DESIGN: In
      this retrospective descriptive study required research projects were assessed for
      frequency of presentation at regional and national meetings or publication in
      medical journals, or both, over a 10-year period (1983 through 1992). Rising
      second-year house officers elected to initiate their own study with departmental
      support under the guidance of a faculty advisor or selected a research project
      from a list of potential investigations offered by departmental faculty. Projects
      were presented at the annual alumni meeting in April of the junior and senior
      years. The faculty advisor assisted in research design, protocol development,
      obtaining human investigation committee approval, data collection, statistical
      analysis, manuscript preparation, and coaching for the oral presentation. After
      local presentation these projects were evaluated for submission to regional and
      national meetings and prepared for peer-review publication. RESULTS: During a 10
      year period 104 resident research projects resulted in 72 regional or national
      presentations and 52 peer-review publications. There was a significant increase
      in the proportion of projects presented at national meetings over time (r = 0.99;
      p < 0.0001). There was also an increase in the number of projects published in
      peer-review journals during the decade-long study period (r = 0.96, p = 0.0001).
      CONCLUSIONS: Required completion of two research studies during residency
      bolstered by early selection of prospective projects and departmental fiscal
      support, as well as intensive faculty advisor direction and assistance, has
      resulted in resident projects with increasingly frequent national recognition.

PMID- 8141201
TI  - Chlamydial serologic studies and recurrent spontaneous abortion.
AB  - OBJECTIVE: Our purpose was to investigate the putative association between
      immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous
      abortions. STUDY DESIGN: Sera from 106 idiopathic recurrent aborters and 81 of
      their partners were tested for immunoglobulin G antichlamydial antibodies by
      whole inclusion immunofluorescence and compared with 3890 sera from a general
      antenatal population. Positive sera were further investigated by
      microimmunofluorescence to determine species (Chlamydia trachomatis, Chlamydia
      pneumoniae, Chlamydia psittaci) specificity. RESULTS: Twenty-six (24.5%) of women
      with recurrent spontaneous abortions had immunoglobulin G antichlamydial
      antibodies compared with 28 (34.6%) of their partners (chi 2 2.25, p < 0.05) and
      788 (20.3%) of the general antenatal population (chi 2 1.16, p < 0.05), and the
      incidence of antibody positivity showed no trend with increasing number of
      previous abortions. Fourteen women with recurrent spontaneous abortions had
      antibodies to Chlamydia trachomatis, 12 to Chlamydia pneumoniae. The prevalence
      of antibodies to C. trachomatis did not differ significantly between women with
      recurrent spontaneous abortions and their partners, but the male partners had a
      significantly (p = 0.005) higher prevalence of Chlamydia pneumoniae antibodies.
      Chlamydial antibody seropositivity did not correlate with subfertility or
      subsequent pregnancy outcome. CONCLUSION: There is no association between
      immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous
      abortion.

PMID- 8141202
TI  - Uterine rupture at 33 weeks' gestation subsequent to hysteroscopic uterine
      perforation.
AB  - A 40-year-old woman underwent operative hysteroscopy for suspected submucosal
      myoma, during which the uterine fundus was perforated. At laparotomy the
      perforation site was sutured. In a subsequent pregnancy she had a sudden onset of
      abdominal pain. Laparotomy revealed a uterine rupture with a partially protruding
      placenta. A healthy newborn was delivered by a low-segment cesarean section.

PMID- 8141203
TI  - Expression of the gap junction protein connexin-43 is increased in the human
      myometrium toward term and with the onset of labor.
AB  - OBJECTIVES: Our aim was to determine the temporal pattern of expression of
      transcripts encoding the myometrial gap junction protein connexin-43 in the human
      myometrium during late pregnancy and with the onset of labor. We also correlated
      these data with levels of total connexin-43 protein and the appearance of gap
      junctions within the myometrial cell membrane. STUDY DESIGN: Myometrial tissue
      was collected during cesarean section from 27 women between 37 and 41 weeks of
      gestation not in labor and from 7 women between 39 and 41 weeks during active
      labor. The levels of connexin-43 messenger ribonucleic acid and protein were
      estimated by Northern and Western analysis, respectively. The appearance of gap
      junctions between myometrial cells was assessed by immunofluorescence of
      histologic sections of myometrium from these women. RESULTS: Levels of connexin
      43 messenger ribonucleic acid in myometrial tissue collected from women not in
      labor increased (p < 0.01) between 37 and 40 weeks' gestation with a further
      significant increase occurring during labor (p < 0.05). The level of connexin-43
      protein decreased (p < 0.05) during late pregnancy and was not increased during
      labor although gap junctions (which were not present during pregnancy) did appear
      in the myometrial cell membrane during labor. CONCLUSIONS: These data suggest
      that the mechanisms responsible for the increased myometrial cell-cell
      communication necessary for the development of effective labor contractions
      likely involves regulation at the level of both messenger ribonucleic acid and
      gap junction formation in the cell membrane.

PMID- 8141204
TI  - Absent end-diastolic velocity in umbilical artery: risk of neonatal morbidity and
      brain damage.
AB  - OBJECTIVE: We conducted a cohort study in growth-retarded fetuses to establish if
      absent or reverse end-diastolic flow in the umbilical artery was associated with
      increased perinatal mortality and morbidity and neurologic damage at long-term
      follow-up. STUDY DESIGN: Thirty-one fetuses with intrauterine growth retardation
      and absent or reverse end-diastolic flow in the umbilical artery (study group)
      and 40 growth-retarded fetuses with detectable diastolic flow in the umbilical
      artery, divided into two control groups, were followed up with serial nonstress
      tests, Doppler flow studies, and biophysical profiles. Twenty newborns from the
      study group survived the perinatal period and were observed for a mean of 18
      months (range 12 to 24 months). Their neurologic outcomes were compared with
      those of 26 neonates from the two control groups. RESULTS: Study group fetuses
      had a higher incidence of abnormal karyotype (9.7% vs 0%) and corrected perinatal
      mortality (26% vs 6% and 4%) and a greater risk of permanent neurologic sequelae
      (35% vs 0% and 12%) compared with the fetuses from the two control groups.
      CONCLUSIONS: Growth-retarded fetuses with absent or reverse end-diastolic flow in
      the umbilical artery not only have an increased fetal and neonatal mortality but
      also a higher incidence of long-term permanent neurologic damage when compared
      with growth-retarded fetuses with diastolic flow in the umbilical circulation.

PMID- 8141205
TI  - Risk factors for recurrent Chlamydia trachomatis infections in women.
AB  - OBJECTIVE: We evaluated risk factors for recurrent Chlamydia trachomatis
      infections in women. STUDY DESIGN: We used a retrospective cohort design to
      examine predictors of recurrent infection in the 38,866 female residents of
      Wisconsin whose first reported C. trachomatis infection occurred between 1985 and
      1989. RESULTS: Young age at first reported infection was the strongest predictor
      of recurrent C. trachomatis infection, after adjustment for covariates.
      Adolescents < 15 years old had an eightfold increased risk, those 15 to 19 years
      old had a fivefold increased risk, and women 20 to 29 years old had a twofold
      increased risk of recurrent C. trachomatis infection, compared with that among
      women 30 to 44 years old. In 54% of those aged < 15 at initial infection and 30%
      of those aged 15 to 19, recurrence developed. Other characteristics associated
      with recurrence included black race, residence in Milwaukee County, coinfection
      with gonorrhea, and past sexually transmitted diseases; receiving care in a
      family-planning clinic appeared protective. CONCLUSIONS: Implementation of
      strategies to reduce the markedly elevated risk of recurrent chlamydia infections
      is urgently needed in female adolescents.

PMID- 8141206
TI  - Molecular analysis of human platelet antigen system 1 antigen on single cells can
      be applied to preimplantation genetic diagnosis for prevention of alloimmune
      thrombocytopenia.
AB  - OBJECTIVE: Our purpose was to develop a molecular assay to determine the human
      platelet antigen system 1 status on single nucleated cells, including human
      blastomeres. STUDY DESIGN: Eighty single cultured lymphoblasts of known human
      platelet antigen system 1 genotype and 24 media blanks were mixed in blinded
      fashion. Amplification of a 246 bp deoxyribonucleic acid fragment and subsequent
      Nci I restriction digestion were performed to distinguish human platelet antigen
      system 1a from 1b alleles. Specificity and sensitivity of the technique were
      determined. Eight blastomeres were also tested. RESULTS: Deoxyribonucleic acid
      amplification at the human platelet antigen system 1 locus was successful in 95%
      of the reactions. No media blanks showed amplified deoxyribonucleic acid. The
      diagnosis was correct in all homozygous human platelet antigen system 1a or 1b
      cells; three of 23 heterozygous cells amplified but failed to digest with Nci I.
      Overall specificity was 95%. All blastomeres successfully amplified. CONCLUSIONS:
      The human platelet antigen system 1 status determination is reliable from a
      single cell and can be used for preimplantation genetic diagnosis for the
      prevention of alloimmune thrombocytopenia.

PMID- 8141207
TI  - Uterus didelphys demonstrated with echo-planar magnetic resonance imaging.

PMID- 8141208
TI  - Ultrasonographic evaluation of central and end-organ hemodynamics in antepartum
      pyelonephritis.
AB  - OBJECTIVE: Our purpose was to evaluate central and end-organ hemodynamic effects
      of antepartum pyelonephritis. STUDY DESIGN: Daily duplex ultrasonographic
      assessments of maternal cardiac output and resistive index values of the maternal
      renal and uterine arteries and the fetal umbilical arteries were performed in
      pregnant women admitted for acute pyelonephritis. For comparison, the same
      measures were repeated within 2 weeks after discharge. RESULTS: Thirty-seven
      women with antepartum pyelonephritis underwent serial 2-dimensional real-time and
      Doppler evaluation of maternal heart and duplex Doppler evaluation of maternal
      renal and uterine and fetal umbilical arteries. Significant differences in
      temperature, mean arterial pressure, and heart rate were observed during
      hospitalization compared with the follow-up visit. Total peripheral resistance
      was significantly decreased and cardiac output increased during acute infection.
      In women with unilateral signs and symptoms an increased resistive index was
      observed in the symptomatic kidney compared with the nonsymptomatic side; this
      difference disappeared on the follow-up study. No changes were observed in
      maternal uterine or fetal umbilical arteries. CONCLUSIONS: Uncomplicated
      pyelonephritis is associated with measurable depression of systemic vascular
      resistance. This likely represents an effect of infection that in the extreme
      would be the septic shock syndrome. It seems reasonable to attribute the
      increased resistive index of the symptomatic kidney to local effects of
      infection.

PMID- 8141209
TI  - Survival of breast cancer patients after subsequent term pregnancy: "healthy
      mother effect".
AB  - OBJECTIVE: A population-based matched survival study was conducted to assess the
      risk of death for breast cancer patients in relation to whether they were
      delivered of a live born child subsequent to the cancer diagnosis. STUDY DESIGN:
      Among the 2548 women < 40 years old diagnosed with carcinoma of the breast in
      1967 to 1989 in Finland there were 91 eligible patients with subsequent
      deliveries (> or = 10 months after the diagnosis) for whom 471 controls were
      matched for stage, age, and year of breast cancer diagnosis. The controls had to
      have survived at least the interval between the diagnosis and the delivery of
      their matched counterparts. The follow-up started from the date of the first
      delivery after the diagnosis or after the corresponding interval for the matched
      controls. A stratified Cox proportional hazards survival analysis was performed.
      RESULTS: The controls had a 4.8-fold (95% confidence interval 2.2 to 10.3) risk
      of death compared with those who were delivered after the diagnosis of breast
      cancer. CONCLUSION: Our interpretation of this result is a "healthy mother
      effect" (i.e., that only women who feel healthy give birth and those who are
      affected by the disease do not). Nevertheless, six of eight deaths among the 91
      patients who did give birth were related to breast cancer.

PMID- 8141210
TI  - Early and simple determination of chorionic and amniotic type in multifetal
      gestations in the first fourteen weeks by high-frequency transvaginal
      ultrasonography.
AB  - OBJECTIVE: Our aim was to determine the chorionic and amniotic types in
      multifetal pregnancies with transvaginal ultrasonography at > or = 14 weeks'
      gestation. STUDY DESIGN: Two hundred twelve multifetal pregnancies were scanned
      transvaginally at or before 14 weeks' gestation. The number of fetuses and the
      chorionic and amniotic type were determined ultrasonographically. Of the 212
      patients, 54 were delivered at our institution, and 43 of these 54 had pathologic
      evaluation of the placenta. Ultrasonographic and pathologic correlation of the
      chorionic and amniotic type was assessed in this group. RESULTS: Ultrasonographic
      evaluation of the 212 pregnancies demonstrated 64 twin, 87 triplet, 41
      quadruplet, 18 quintuplet, 1 sextuplet, and 1 septuplet gestation. Nine of the
      twin pregnancies were monochorionic-diamniotic; two of the triplets were
      dichorionic-triamniotic, and four of the quadruplets were trichorionic
      quadraamniotic. In the 43 patients with both ultrasonographic and pathologic
      assessment, there were 40 twins, five of which were monochoronic diamniotic type.
      All three triplets were trichorionic-triamniotic type. In all 43 transvaginal
      ultrasonography correctly predicted the chorionic and amniotic type as determined
      by the pathologic findings. CONCLUSIONS: Transvaginal ultrasonography at < or =
      14 weeks can easily and accurately determine the chorionic and amniotic type in
      multifetal pregnancies.

PMID- 8141211
TI  - A randomized, prospective trial comparing amoxicillin and erythromycin for the
      treatment of Chlamydia trachomatis in pregnancy.
AB  - OBJECTIVE: Our purpose was to evaluate the efficacy of amoxicillin as an
      alternative therapy to erythromycin for the treatment of cervical chlamydial
      infections during pregnancy. STUDY DESIGN: A randomized, prospective trial of two
      treatment regimens for Chlamydia trachomatis was performed in a cohort of
      pregnant women enrolled for care in an inner-city, university-based prenatal
      clinic, with an alternate-therapy crossover arm for primary treatment failures.
      Pregnant women diagnosed with chlamydial infection by McCoy cell culture of
      cervical swabs were assigned to receive either 500 mg of amoxicillin three times
      daily or 500 mg of erythromycin four times daily for 7 days. Patients' partners
      were treated with doxycycline. Compliance information was obtained by a
      standardized questionnaire at a posttherapy follow-up visit. Patients with
      positive follow-up cultures were crossed over into the alternate treatment arm
      and recultured at a later visit. RESULTS: During the study period 74 women
      consented to participate in this trial; 36 were treated with amoxicillin and 38
      with erythromycin. Initial cure rates of 82.3% (28/34) for the amoxicillin group
      and 84.6% (27/32) for erythromycin were obtained before crossover (p = 0.91);
      four patients in each group were lost to follow-up. Overall cure rates after
      crossover were 84.6% (33/39) for amoxicillin and 84.2% (32/38) for erythromycin
      (p = 0.83). In the amoxicillin group 12.8% of patients reported side effects
      compared with 31.6% treated with erythromycin (p = 0.09), although seven
      erythromycin-treated patients compared with none of those in the amoxicillin arm
      stopped therapy because of side effects (p = 0.02). CONCLUSION: Amoxicillin
      offers a reasonable alternative to erythromycin for the treatment of Chlamydia
      trachomatis in pregnancy, on the basis of both cure rates and patient compliance.

PMID- 8141212
TI  - Gynecologic manifestations of Sjogren's syndrome.
AB  - OBJECTIVE: Sjogren's syndrome is a chronic, inflammatory autoimmune disease in
      which the salivary and lacrimal glands are progressively destroyed by lymphocytes
      and plasma cells. Because women are affected 10 times more often than men, we
      studied gynecologic manifestations of Sjogren's syndrome. STUDY DESIGN: One
      thousand questionnaires were sent to women with Sjogren's syndrome in New York,
      New Jersey, Connecticut, and Pennsylvania. Five hundred thirty-nine women
      responded. RESULTS: Women with Sjogren's syndrome reported significant vaginal
      dryness. There was no relationship of Sjogren's syndrome to either the incidence
      of infertility or miscarriage, although the 4% incidence of congenital anomalies
      in offspring was relatively high. Of the congenital anomalies, nine of 19 (47%)
      were cardiac. A long menstrual cycle (> 35 days) was associated with infertility
      and neuropathy. CONCLUSIONS: The vaginal dryness in women with Sjogren's syndrome
      is not surprising, because the nasal and esophageal mucosae are also dry in this
      disorder. The relationship of infertility to a long menstrual cycle may simply
      indicate the presence of ovulatory dysfunction or inadequate luteal phase
      unrelated to Sjogren's syndrome. The relationship of neuropathy to a long
      menstrual cycle may be related to repeated, prolonged estrogen or progesterone
      exposure during the long cycles or to involvement of hypothalamic-pituitary
      ovarian function.

PMID- 8141213
TI  - Plasma cellular fibronectin as a measure of endothelial involvement in
      preeclampsia and intrauterine growth retardation.
AB  - OBJECTIVE: Our purpose was to determine the presence and degree of endothelial
      injury, by measuring plasma concentrations of cellular fibronectin, in
      pregnancies complicated by preeclampsia or intrauterine growth retardation. STUDY
      DESIGN: A matched, nested, case-control study design was used. Plasma was
      collected prospectively from pregnant women throughout gestation. At least 12
      weeks after delivery women with preeclampsia, both preeclampsia and intrauterine
      growth retardation, or intrauterine growth retardation alone were identified.
      Normal controls were matched to these patients by age, race, and gestational age.
      Stored plasma, which had been obtained in the third trimester, was assayed for
      cellular fibronectin by means of a sensitive and specific enzyme immunoassay.
      After an appropriate transformation of the data results were compared with one
      way analysis of variance with Fisher's post hoc test. RESULTS: Patients with
      preeclampsia (n = 18) had higher plasma cellular fibronectin concentrations than
      did control patients (n = 68) with median values of 2.8 and 1.4 micrograms/ml,
      respectively (p < 0.001, using transformed data). Patients with intrauterine
      growth retardation alone (n = 10) had 2.3 micrograms/ml cellular fibronectin,
      significantly higher than values of controls (p < 0.02 using transformed data)
      and significantly lower than those of patients with preeclampsia (p < 0.05 using
      transformed data). CONCLUSION: Pregnancies complicated by preeclampsia had
      significantly higher plasma cellular fibronectin concentrations than did
      pregnancies with intrauterine growth retardation alone, which in turn had
      significantly higher plasma cellular fibronectin concentrations than did control
      pregnancies. We speculate that endothelial involvement in intrauterine growth
      retardation is confined to the uteroplacental circulation, whereas it is systemic
      in preeclampsia.

PMID- 8141214
TI  - Amnioinfusion during labor complicated by particulate meconium-stained amniotic
      fluid decreases neonatal morbidity.
AB  - OBJECTIVE: Our purpose was to evaluate the efficacy of prophylactic amnioinfusion
      in decreasing neonatal morbidity associated with labor complicated by particulate
      meconium-stained amniotic fluid and to assess potential complications of this
      procedure. STUDY DESIGN: One hundred five laboring pregnant women with
      particulate (moderate or thick) meconium by subjective clinical analysis were
      randomly assigned to receive amnioinfusion or to receive standard obstetric care
      without amnioinfusion. Patients with any antepartum complications, other than the
      presence of meconium, were excluded from the study. Statistical analyses
      consisted of the two-tailed and paired Student t tests, Pearson chi 2 test, and
      Wilcoxon nonparametric test. Significance was set at p < 0.05. RESULTS: The study
      included 47 patients in the study group and 58 patients in the control group. A
      significantly greater proportion of study patients demonstrated decreased
      meconium concentration between rupture of membranes and delivery (46 of 46 vs 15
      of 58, p < 0.001). The relative dilution of meconium consistency by objective
      analysis was significantly different between the study group and the control
      group (77.1% decrease vs 9.3% increase, p < 0.001). The proportion of neonates
      with meconium below the vocal cords was reduced in the study group (two of 47 vs
      36 of 58, p < 0.001). Umbilical artery pH was increased in the study group
      neonates (7.29 +/- 0.01 vs 7.25 +/- 0.009, p < 0.05). The rate of neonatal
      acidemia was reduced in the study group (4 of 45 vs 12 of 50, p < 0.05). The rate
      of meconium aspiration syndrome was reduced in the study group (1 of 47 vs 8 of
      58, p < 0.05). Maternal and neonatal morbidity rates were similar. CONCLUSION:
      Prophylactic amnioinfusion should be considered a possible addition to the
      intrapartum management of patients with particulate meconium-stained amniotic
      fluid.

PMID- 8141215
TI  - A longitudinal study of cardiac output in normal human pregnancy.
AB  - OBJECTIVE: Our purpose was to investigate the maternal hemodynamic and cardiac
      structural changes that occur during pregnancy. STUDY DESIGN: Eighteen women
      underwent serial echocardiography beginning at 8 to 11 weeks' gestation, then at
      monthly intervals throughout pregnancy and at 6 and 12 weeks post partum. Cardiac
      output was measured by pulsed- and continuous-wave Doppler at the aortic valve.
      Left ventricular chamber size, wall thickness, and mass were determined by M-mode
      echocardiography. Ventricular diastolic function was assessed by Doppler
      recording of mitral inflow. RESULTS: Cardiac output by pulsed Doppler increased
      from 6.7 +/- 0.6 L/min at 8 to 11 weeks' gestation to 8.7 +/- 1.4 L/min at 36 to
      39 weeks' gestation before falling to 5.7 +/- 0.7 L/min 12 weeks post partum.
      Heart rate increased 29%, and stroke volume increased 18%. Left ventricular mass
      increased because of an increase in wall thickness. Peak mitral A wave velocity
      increased in late pregnancy. Cardiac output by pulsed and continuous-wave Doppler
      was similar. CONCLUSION: Cardiac output continues to increase even in late
      pregnancy. Left ventricular mass increases because of increased wall thickness.
      The mitral flow velocity findings suggested decreased ventricular compliance or
      increased preload.

PMID- 8141216
TI  - Vaginal lactobacillosis.
AB  - OBJECTIVES: Our purpose was to study a cyclic condition characterized by vaginal
      discharge and discomfort occurring 7 to 10 days before menses and associated with
      the occurrence of long serpiginous rodlike organisms, visible in wet mount
      preparations. STUDY DESIGN: Thirty-seven patients and 30 controls were studied
      prospectively. The vaginal flora was analyzed, including isolation of anaerobic
      bacteria and fungi. Species of lactobacilli isolated from some of the women were
      identified and the antibiotic susceptibility was determined. Recent episodes of
      vaginitis and therapy were recorded. RESULTS: Ninety-two percent of the patients
      had a history of recent episodes of vaginosis lasting for an average of 22.2
      months, and 57% had received triazole or imidazole antifungal therapy. Anaerobic
      lactobacilli were isolated from 97% of the vaginosis patients and from 40% of the
      controls. The average length of the organism seen was 60 microns in the patients
      and 10 microns in the comparison group. Amoxicillin and clavulanate potassium
      proved to be an effective therapy symptomatically and resulted in disappearance
      of the extremely long organisms in vaginal smears. CONCLUSIONS: Lactobacilli
      vaginosis is associated with extremely long lactobacilli. The cause of this
      morphologic transformation is unknown. The condition can be effectively treated
      with antibiotics.

PMID- 8141217
TI  - A prospective study of heparin-induced osteoporosis in pregnancy using bone
      densitometry.
AB  - OBJECTIVE: Our purpose was to evaluate the subclinical occurrence of heparin
      induced osteoporosis in pregnancy, by means of bone densitometry. STUDY DESIGN: A
      prospective, consecutive cohort of 14 pregnant women requiring heparin therapy
      and 14 pregnant controls matched for age, race, and smoking status was identified
      by 20 weeks' gestation at a university medical center. Proximal femur bone
      density measurements were taken at baseline, immediately post partum, and 6
      months post partum in the cases and controls. Vertebral measurements were also
      obtained on both groups immediately post partum and 6 months post partum. Bone
      density as a function of heparin dosing and duration was examined. Nonparametric
      statistical tests were used for all comparisons. RESULTS: Five of 14 cases (36%)
      had a > or = 10% decrease from the baseline proximal femur measurements to
      immediate postpartum values versus none of the 14 matched controls (p = 0.04).
      Mean proximal femur bone density measurements also decreased in the cases (p =
      0.01); this difference continued to be statistically significant 6 months post
      partum (p = 0.03). No dose-response relationship could be demonstrated.
      CONCLUSION: Heparin adversely affected bone density in about one third of exposed
      patients.

PMID- 8141218
TI  - The effect of corticosteroid therapy in the very premature infant. March of Dimes
      Multicenter Study Group.
AB  - OBJECTIVE: Our purpose was to determine the efficacy of maternal corticosteroid
      therapy between 26 and 31 weeks' gestation. STUDY DESIGN: The data in this study
      were derived from 32,658 women who participated in the March of Dimes-sponsored
      multicenter prematurity prevention program. Of the 432 women who were delivered
      at 26 to 31 weeks, 67 received betamethasone before delivery and 365 did not. The
      frequency and relative risks of adverse outcomes, including respiratory distress
      syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal
      death were compared for each of two gestational age periods by means of
      univariate and multivariate techniques. RESULTS: When betamethasone was
      administered > or = 2 days before delivery (n = 45), there was a lower incidence
      of respiratory distress syndrome in both the 26 to 28 week group (53.9% vs 86.5%,
      p = 0.008) and the 29 to 31 week group (25.0% vs 59.1%, p = 0.0003). The rate of
      intraventricular hemorrhage was less in the betamethasone group at 26 to 28 weeks
      (15.4% vs 32.3%, p = 0.17), but the difference reached statistical significance
      only at 29 to 31 weeks (3.1% vs 16.5%, p = 0.029). Neonatal death occurred
      significantly less often in infants who were delivered at 26 to 28 weeks when
      their mothers received betamethasone compared with infants of the same
      gestational age whose mothers did not receive betamethasone treatment (0% vs
      34.6%, p = 0.01). In a regression analysis of infants born between 26 and 31
      weeks in which birth weight, gestational age, race, infant sex, and tocolytic use
      were controlled, the odds ratio for respiratory distress syndrome associated with
      betamethasone use was 0.20 (0.10, 0.42), for intraventricular hemorrhage 0.26
      (0.08, 0.90), and for neonatal death 0.14 (0.02, 1.09). Insufficient numbers of
      women were given betamethasone before 26 weeks for analysis. CONCLUSION:
      Betamethasone appears to significantly reduce neonatal death and the morbidity
      between 26 and 31 weeks' gestation.

PMID- 8141219
TI  - A prospective comparison of the outcome of triplet pregnancies managed
      expectantly or by multifetal reduction to twins.
AB  - OBJECTIVE: Our aim was to compare the outcome of triplet pregnancies managed
      expectantly or by multifetal reduction to twins. STUDY DESIGN: From January 1984
      through January 1992, 140 triplet gestations were diagnosed before the ninth
      gestational week. Multifetal pregnancy reduction was performed at the patient's
      request in 34 women. The remaining 106 triplet pregnancies were managed
      expectantly. All patients were prospectively followed up and delivered in a
      single perinatal department. RESULTS: Loss of the entire pregnancy before 25
      gestational weeks occurred in 20.7% of the triplet pregnancies managed
      expectantly as compared with 8.7% in the group with reduction to twins. A
      successful pregnancy as defined by the discharge home of at least one infant
      occurred in 88.2% of the group with reduction to twins and 74.5% of the triplets
      managed expectantly. Fetal reduction to twins was associated with a significantly
      lower incidence of the following: prematurity (p < 0.001), low-birth-weight
      infants (p < 0.001), and very-low-birth-weight infants (p < 0.001). Pregnancy
      complications and neonatal morbidity and mortality were less in the group with
      reduction to twins. CONCLUSIONS: Multifetal pregnancy reduction of triplet
      pregnancies to twins resulted in improved pregnancy outcome without an excess
      loss of the entire pregnancy as compared with the outcome of triplet gestations
      managed expectantly.

PMID- 8141220
TI  - The effect of breast-feeding frequency on serum bilirubin levels.
AB  - OBJECTIVE: Our purpose was to evaluate the effect of breast-feeding frequency on
      serum bilirubin levels in the first 3 days after birth. STUDY DESIGN: Two hundred
      seventy-five infants were randomly assigned to a frequent or demand breast
      feeding schedule. RESULTS: Infants in the frequent group (n = 131) nursed nine
      (7.5 to 10.5) times per day (median and inner 80%), and the demand group (n =
      143) fed 6.5 (5.5 to 8.0) times per day. The serum bilirubin level was measured
      in all infants between 48 and 80 hours (median 53 hours, inner 80% 48 to 68
      hours) and was 7.4 (1.8 to 10.7) mg/dl in the frequent group and 8.0 (2.9 to
      11.2) mg/dl in the demand group (p = 0.103). There was no correlation between the
      frequency of breast-feeding and the serum bilirubin level. CONCLUSION: Within the
      range of the frequency of nursing observed in this study, we could not
      demonstrate a significant effect on serum bilirubin levels in the first 3 days
      after birth.

PMID- 8141221
TI  - The relationship between exposure during pregnancy to cigarette smoking and
      cocaine use and placenta previa.
AB  - OBJECTIVE: This study examined the relationship between two maternal exposures,
      cigarette smoking and cocaine use, and placenta previa. STUDY DESIGN: A hospital
      based case-control study was conducted. Three hundred four cases of placenta
      previa were compared with 2732 controls with respect to demographic
      characteristics, substance use, and perinatal characteristics. Logistic
      regression was used to examine the individual effects of cigarette smoking and
      cocaine use on placenta previa, independent of other known risk factors. RESULTS:
      A dose-response relationship between smoking cigarettes and placenta previa was
      observed independent of other known risk factors (ptrend < 0.01). Pregnant women
      who smoked > or = 20 cigarettes per day were over two times more likely to
      experience a placenta previa relative to nonsmokers (odds ratio 2.3, 95%
      confidence interval 1.5 to 3.5). Pregnant women who used cocaine were 1.4 times
      (95% confidence interval 0.8 to 2.4) as likely to experience a placenta previa as
      nonusers. CONCLUSIONS: The previously observed association between smoking and
      placenta previa is supported by the dose-response relationship observed in this
      study. The potential association of cocaine with placenta previa needs more
      exploration.

PMID- 8141222
TI  - Intrahepatic cholestasis of pregnancy: a retrospective case-control study of
      perinatal outcome.
AB  - OBJECTIVES: Intrahepatic cholestasis of pregnancy has been related to a high
      frequency of abnormal intrapartum fetal heart rate, amniotic fluid meconium,
      prematurity, and perinatal mortality. To determine whether these adverse
      perinatal outcomes could be improved with active intervention, we evaluated our
      results. STUDY DESIGN: We report a retrospective case-control study of 320
      consecutive patients with intrahepatic cholestasis of pregnancy management with
      antepartum testing and active intervention over a 2-year period. RESULTS: Our
      results indicate a higher incidence of meconium staining in amniotic fluid at
      delivery (25% vs 16%, p < 0.05) and spontaneous preterm delivery (12.1% vs 3.9%,
      p < 0.05), without an increase in the frequency of abnormal intrapartum fetal
      heart rate (12% vs 11%, not significant), 5-minute Apgar score < 7 (2.0% vs 1.0%,
      not significant), or perinatal mortality (18/1000 vs 13/1000, not significant).
      CONCLUSION: Antenatal testing and timed intervention of patients with
      intrahepatic cholestasis of pregnancy is associated with a reduction of the
      previously reported adverse perinatal outcomes.

PMID- 8141223
TI  - Maternal erythropoietin in singleton pregnancies: a randomized trial on the
      effect of oral hematinic supplementation.
AB  - OBJECTIVE: Our purpose was to study the effect of hematinic supplementation on
      the maternal erythropoietin response during singleton pregnancy. STUDY DESIGN: In
      a randomized, double-blind trial 97 patients with a first-trimester hemoglobin
      level > or = 14.0 gm/dl received either iron and folic acid (hematinic group, n =
      53) or a placebo (n = 44). Serial hemoglobin, hematocrit, and serum
      erythropoietin were recorded from maternal blood and from cord blood on delivery.
      Serum ferritin was measured in the first trimester, at 36 weeks' gestation, and
      in cord blood. RESULTS: In both groups (1) the mean hemoglobin was lower (p <
      0.01) at 40 weeks' gestation than when first examined and (2) the mean serum
      erythropoietin was higher (p < 0.01). The mean serum ferritin was lower (p <
      0.001) in both groups at 36 weeks' gestation than at presentation but higher (p =
      0.04) in the hematinic group than in the placebo group. The mean hemoglobin and
      hematocrit were similar in the two groups until the third trimester but
      thereafter were higher (p < 0.05) in the hematinic group. The mean maternal serum
      erythropoietin was higher (p < 0.05) in the placebo group than in the hematinic
      group after 24 weeks' gestation. The mean cord blood hematologic values were
      similar in the two groups. CONCLUSION: Maternal serum erythropoietin increased
      during pregnancy, but this response was reduced in the third trimester in the
      hematinic-supplemented group.

PMID- 8141224
TI  - Transabdominal versus transcervical and transvaginal multifetal pregnancy
      reduction: international collaborative experience of more than one thousand
      cases.
AB  - OBJECTIVES: Two major approaches for multifetal pregnancy reduction have been
      developed over the past several years: transabdominal potassium chloride by
      injection and pelvic procedures by either transcervical aspiration or
      transvaginal potassium chloride injection or by an automated spring-loaded
      puncture device. The purpose of this study was to create the largest database
      from among the world's largest centers to assess possible differences in efficacy
      and complication rates by transabdominal or transcervical or multifetal pregnancy
      reduction. STUDY DESIGN: Data on over 1000 completed pregnancies that underwent
      multifetal pregnancy reduction by both methods from major centers with among the
      highest worldwide experience were combined. Transabdominal cases were divided
      temporally (1986 through 1991 and 1991 through 1993). RESULTS: Transabdominal
      multifetal pregnancy reduction was successfully performed on 846 patients and
      transcervical or transvaginal on 238 patients. Transcervical or transvaginal
      reduction is performed earlier and starts and finishes with fewer embryos. In
      12.6% of cases transcervical or transvaginal reduction left a singleton as
      opposed to 4.4% for transabdominal reduction. Pregnancy losses (up to 24 weeks)
      were observed in 13.1% of transcervical or transvaginal cases and in 16.2% of
      transabdominal cases early in the series and 8.8% of late transabdominal cases.
      Transcervical or transvaginal reduction may be safer very early in gestation and
      transabdominal safer later in the first trimester. Premature deliveries were
      comparable, with only about 5% delivered between 25 and 28 weeks. The smaller
      starting numbers for transcervical and transvaginal reduction may explain a
      slightly higher term delivery rate. The transabdominal route tends to reduce the
      fundal embryos and the transcervical and transvaginal the lower ones. The
      significance of this is not clear. CONCLUSIONS: (1) Multifetal pregnancy
      reduction by either method is a relatively safe and efficient method for
      improving outcome in multifetal pregnancies. (2) More than 84% are delivered at >
      33 weeks. (3) The experience and preference of the operator are probably the key
      determinants for an individual patient. (4) An inverse relationship of starting
      and finishing number to loss rates and gestational age at delivery suggests that
      there still is a cost of iatrogenic multifetal pregnancies, even if multifetal
      pregnancy reduction can be successfully performed.

PMID- 8141225
TI  - Intrapartum chemoprophylaxis of perinatal group B streptococcal infections: a
      critical review of randomized controlled trials.
AB  - The purpose of this overview was to critically appraise all published randomized,
      controlled trials evaluating the efficacy of intrapartum chemoprophylaxis in
      reducing perinatal group B streptococcal infections. The Oxford Database of
      Perinatal Trials, Medline, Excerpta Medica, and personal files were used for the
      literature search. By means of present inclusion criteria to select relevant
      articles, two independent researchers identified nine randomized, controlled
      trials. Three trials were excluded because of duplicate publication, one because
      the randomization process was violated, and one because the outcome data were
      collected retrospectively. The quality of the methods of the four accepted trials
      was poor, and because of basic flaws meta-analyses of trial results were not
      performed. Results of three studies showed a statistically significant reduction
      in neonatal group B streptococcal colonization rates with intrapartum
      chemoprophylaxis. Although a trend toward a reduction in proved neonatal
      infection was reported in three studies, each lacked the power to reach
      statistical significance. Intrapartum chemoprophylaxis to reduce perinatal group
      B streptococcal infections is not supported by conclusive evidence from well
      designed and conducted randomized, controlled trials.

PMID- 8141226
TI  - Levels of soluble interleukin-2 receptor-alpha are elevated in serum and ascitic
      fluid from epithelial ovarian cancer patients.
AB  - OBJECTIVE: The purpose of the study was to determine whether ovarian cancer
      patients have activated lymphocytes as indicated by the presence of soluble
      interleukin-2 receptor-alpha and to compare soluble interleukin-2 receptor-alpha
      with other markers in ovarian cancer. STUDY DESIGN: Ascites and serum from
      patients with advanced active ovarian cancer was tested for the presence of
      elevated levels of soluble interleukin-2 receptor-alpha and compared with normal
      controls. Levels of soluble interleukin-2 receptor-alpha were also compared with
      levels of CA 125 and macrophage colony-stimulating factor in the same patients,
      to evaluate the correlation between different markers. RESULTS: Elevated levels
      of soluble interleukin-2 receptor-alpha were detected in 86 of 86 (100%) ascites
      samples and 67 of 85 (79%) serum samples from patients with advanced epithelial
      ovarian cancer. In contrast, only 12 of 25 (48%) benign ascites samples and one
      of 88 (1%) serum samples from controls had elevated levels. There was no obvious
      correlation between levels of soluble interleukin-2 receptor-alpha and levels of
      CA 125; however, levels of soluble interleukin-2 receptor-alpha did correlate
      with levels of macrophage colony-stimulating factor. Concurrent measurement of
      serum-soluble interleukin-2 alpha and CA 125 levels detected 100% of patients
      with epithelial ovarian cancer. CONCLUSION: The detection of elevated levels of
      soluble interleukin-2 receptor-alpha in serum and ascites indicates the presence
      of activated lymphocytes in patients with epithelial ovarian cancer. Ascites and
      serum levels of soluble interleukin-2 receptor-alpha are elevated in patients
      with advanced ovarian cancer and warrant assessment as a potential complementary
      marker to CA 125 for early detection of ovarian cancer and management of patients
      with advanced ovarian cancer.

PMID- 8141227
TI  - Fetal endocrine responses to chronic placental embolization in the late-gestation
      ovine fetus.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of chronic fetal
      placental embolization on the fetal corticotropin, cortisol, and catecholamines
      concentrations and on myometrial contractility pattern. STUDY DESIGN: Fourteen
      fetal sheep were studied (seven embolized, seven controls) for 10 days between
      0.84 and 0.91 of gestation. Daily injections of nonradioactive microspheres were
      performed to decrease fetal arterial oxygen content by 30% to 35% of the
      preembolization value. Umbilical artery Doppler flow velocity waveforms were
      measured daily. RESULTS: Chronic fetal placental embolization produced
      progressive fetal hypoxemia (p < 0.001) with changes in umbilical artery Doppler
      flow velocity waveforms indicative of a 25% increase in placental vascular
      resistance (p < 0.01). In response to chronic fetal hypoxemia there was a
      progressive increase in baseline fetal plasma norepinephrine concentration (p <
      0.001). There was a transient fourfold to fivefold increase in baseline fetal
      plasma cortisol levels concomitant with a significant decrease in baseline
      immunoreactive corticotropin between days 7 and 9 of embolization (both p <
      0.05), with a return to control values by day 10. There was a 57% increase in
      myometrial contracture frequency in the embolized group when compared with
      controls (p = 0.001). CONCLUSIONS: During repetitive chronic placental damage
      that led to fetal hypoxemia, the fetal endocrine environment changed with time in
      a direction that would prevent the onset of premature activation of the
      hypothalamic-pituitary-adrenal axis and premature delivery.

PMID- 8141228
TI  - Cerebral metabolism during sustained hypoxemia in preterm fetal sheep.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of sustained
      hypoxia with resulting metabolic acidosis on cerebral metabolism in the preterm
      ovine fetus. STUDY DESIGN: Twelve fetal sheep were studied at 0.75 of gestation
      during a normoxic control period, after 1 and 8 hours of sustained hypoxemia, and
      again after a 1-hour recovery period. Cerebral arteriovenous differences were
      analyzed for oxygen content, blood gases and pH, glucose, and lactate. Cerebral
      blood flow was measured with the microsphere technique. RESULTS: Induced
      hypoxemia resulted in a variable degree of fetal acidemia that was entirely
      metabolic. Although cerebral oxidative metabolism was well maintained throughout
      the study, cerebral glucose consumption was variably increased when measured
      after 1 hour of sustained hypoxemia, with a subsequent decrease after 1 hour of
      recovery. Although lactate was neither consumed nor produced during the control
      period, by 8 hours of hypoxic study a significant efflux of lactate from the
      brain was evident, which continued into the recovery period. CONCLUSION:
      Sustained hypoxemia results in an increase in the anaerobic metabolism of glucose
      by the preterm fetal brain independent of any change in cerebral oxidative
      metabolism, which may give rise to an accumulation of lactic acid and contribute
      to neurologic impairment.

PMID- 8141229
TI  - Functional characteristics of small placental arteries.
AB  - OBJECTIVES: The aim of this study was to investigate characteristics of placental
      arteries capable of influencing vasomotor tone in the fetoplacental vascular bed.
      Contractile characteristics and endothelium-dependent and endothelium-independent
      relaxation were examined. STUDY DESIGN: By means of a small vessel myograph
      arteries of mean normalized internal diameter 353.22 +/- 13.14 microns were
      studied under isometric conditions. Contractile function was assessed with a
      variety of agonists, including angiotensin II, endothelin-1, the thromboxane
      mimetic U46619, prostaglandin E2, and prostaglandin F2 alpha. The effect of
      physiologic and supraphysiologic PO2 on vascular function was also examined.
      Relaxation was assessed in response to known endothelium-dependent vasodilators,
      including acetylcholine, bradykinin, histamine, and A23187 and to sodium
      nitroprusside (endothelium independent). The effect of indomethacin and the
      nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester on contractile
      function was also evaluated. RESULTS: Sensitivity to sodium nitroprusside was
      reduced by a high PO2. U46619 was the most potent constrictor agonist studied.
      The response of precontracted arteries to known endothelium-dependent
      vasodilators was minimal, other than for histamine, which led to modest
      relaxation. The constrictor response to U46619 was increased in the presence of
      NG-nitro-L-arginine methyl ester. CONCLUSIONS: Oxygen tension may be an important
      determinant of relaxation in small placental arteries. Receptor-mediated release
      of endothelium-derived relaxing factor is not a major mechanism in the
      fetoplacental circulation.

PMID- 8141230
TI  - Improved detection of fetal cells from maternal blood with polymerase chain
      reaction.
AB  - OBJECTIVE: The objective was to test the reliability of new deoxyribonucleic acid
      primers that have previously been used very efficiently by this laboratory with
      amniolysate samples to amplify a 248 bp Y-specific, repeated sequence from
      maternal blood during pregnancy. STUDY DESIGN: Blood samples were obtained from
      50 women during weeks 11 and 16 of pregnancy and were analyzed for the presence
      of the Y chromosome-specific sequences. RESULTS: Y-specific fragments were
      identified in 19 of 24 (79.2%) women after one complete amplification. A second
      amplification of these samples negative for Y-specific fragments revealed three
      additional samples positive for the Y chromosome-specific fragment. Only two male
      fetuses remained unidentified. Overall, 91.7% male fetuses and 96% of all fetuses
      (48/50) in these women were correctly identified. CONCLUSIONS: The primers
      described in this study provide an additional or alternative tool for the
      determination, by means of the polymerase chain reaction, of Y chromosome-bearing
      cells in maternal circulation.

PMID- 8141231
TI  - McDonald cerclage and cervical innervation.

PMID- 8141232
TI  - Antithyroid antibodies in recurrent pregnancy loss.

PMID- 8141233
TI  - Deoxyribonucleic acid analysis of trophoblastic tumors.

PMID- 8141234
TI  - Corpus luteum dysfunction--is the treatment really ineffective?

PMID- 8141235
TI  - Acidemia associated with the use of high-flow insufflators during laparoscopy.

PMID- 8141236
TI  - Black or white--revisited.

PMID- 8141237
TI  - Survival near the limit of viability is much improved.

PMID- 8141238
TI  - Postcranial robusticity in Homo. II: Humeral bilateral asymmetry and bone
      plasticity.
AB  - The analysis of humeral asymmetry in Recent human skeletal samples and an extant
      tennis-player sample documents minimal asymmetry in bone length, little asymmetry
      in distal humeral articular breadth, but pronounced and variable asymmetry in mid
      and distal diaphyseal cross-sectional geometric parameters. More specifically,
      skeletal samples of normal modern Euroamericans, prehistoric and early historic
      Amerindians, and prehistoric Japanese show moderate (ca. 5-14%) median asymmetry
      in diaphyseal cross-sectional areas and polar second moments of area, whereas the
      tennis-player sample, with pronounced unilateral physical activity, exhibits
      median asymmetries of 28-57% in the same parameters. A sample of Neandertals with
      nonpathological upper limbs exhibits similarly low articular asymmetry but
      pronounced diaphyseal asymmetries, averaging 24-57%. In addition, three
      Neandertals with actual or possible post-traumatic upper limb alterations have
      the same low articular asymmetry but extremely high diaphyseal asymmetries,
      averaging 112-215%. These data support those from experimental work on animals,
      exercise programs of humans, and human clinical contexts in establishing the high
      degree of diaphyseal plasticity possible for humans, past and present, under
      changing biomechanical loading conditions. This lends support to activity-related
      functional interpretations of changing human diaphyseal morphology and
      robusticity during the Pleistocene.

PMID- 8141239
TI  - Linear densitometry and digital image processing of proximal femur radiographs:
      implications for archaeological and forensic anthropology.
AB  - Age- and sex-related patterns of proximal femur trabecular bone loss have
      previously been used to establish radiographic reference standards for estimating
      age at death for human skeletal remains. Such standards are of interest to both
      anthropologists and forensic scientists. However, osteopenia as a physiological
      phenomenon is dependent on numerous genetic, environmental, and cultural factors.
      Thus, while general age- and sex-related trends can be clearly observed for
      trabecular bone loss, such patterns also demonstrate marked variation among
      individuals of both sexes at all ages. Moreover, clinical evidence shows that
      rates of bone loss are not steady but episodic, and that radiographically
      "normal" (i.e., young adult) patterns of trabecular bone architecture can also
      exist in femora of older individuals, particularly within samples of African
      origin. In this study, adult proximal femur radiographs were used to explore
      patterns of age- and sex-related proximal femur cancellous bone involution among
      a sample of 66 African-American individuals from the Terry collection (33 males
      and 33 females), ranging in age from 19 to 71 years. The proximal femur
      radiographs of these subjects were analyzed by digital image processing (DIP),
      and the results were compared to those obtained by laser linear densitometric
      analyses (LDA) previously performed on the same series (Macchiarelli et al.,
      1987). Results of LDA and DIP analyses indicate (a) more pronounced bone density
      decrease in females; (b) sex- and site-specific structural patterns of proximal
      femur trabecular bone loss; (c) a high level of individual variability, in which
      predicted age deviated from real age by as much as 22.26 (males) and 30.78 years
      (females); (d) a moderate linear correlation with age for all the variables
      analyzed; and (e) an average discrepancy between known age and predicted age
      (measured by root mean squared residual values) of 10.34 (males) and 12.71 years
      (females) for the most satisfactory DIP analysis parameter (recorded at the
      center of the femoral neck in the equalized images). With regard to estimating
      adult age at death from radiographic images of proximal femora, it is argued that
      the amount of useful age information reported for this criterion has been
      overestimated.

PMID- 8141240
TI  - Brief communication: bone remodeling rates: a test of an algorithm for estimating
      missing osteons.
AB  - Frost (1987a) proposed an algorithm for estimating the number of missing osteons
      that correspond to observed osteon population densities (OPD). Such an algorithm
      should allow more accurate estimates of bone remodeling rates for skeletal
      remains for which in vivo labeling is not possible. In order to validate the
      algorithm, it was tested on an autopsy sample of 44 ribs. Estimates of activation
      frequency (mu RC) and bone remodeling rate (Vf,r,t) using the new algorithm are
      in reasonable agreement with age-matched tetracycline-based values. Although mean
      values for activation frequencies (mu RC) and bone formation rate (Vf,r,t)
      generated by the algorithm were generally lower, they fell below 1 standard error
      for only an age category that included all ages above the 5th decade. It is now
      appropriate to apply the algorithm to archaeological skeletal remains.

PMID- 8141241
TI  - Postcranial robusticity in Homo. III: Ontogeny.
AB  - The influence of developmental factors on long-bone cross-sectional geometry and
      articular size in modern humans is investigated using two approaches: (1) an
      analysis of the effects of increased mechanical loading on long-bone structure
      when applied during different developmental periods, using data collected for a
      study of upper limb bone bilateral asymmetry in professional tennis players; and
      (2) an analysis of the relative timing of age changes in femoral dimensions among
      juveniles from the Pecos Pueblo Amerindian archaeological sample. Results of
      these analyses are used to interpret the femoral morphology of three pre-Recent
      Homo juveniles--the H. erectus KNM-WT 15000 and the archaic H. sapiens La
      Ferrassie 6 and Teshik-Tash 1--as well as observed differences in postcranial
      morphology between adult Recent and earlier Homo (Ruff et al., 1993). Our
      findings indicate the following: (1) There are age-related changes in long-bone
      diaphyseal envelope sensitivity to increased mechanical loading, with the
      periosteal envelope more responsive prior to mid-adolescence, and the endosteal
      envelope more responsive thereafter. The periosteal expansion and endosteal
      contraction of the diaphysis documented earlier for adult pre-Recent Homo
      relative to Recent humans (Ruff et al., 1993) is thus consistent with a
      developmental response to increased mechanical loading applied throughout life.
      The relatively large medullary cavity in the 11-12-year-old KNM-WT 15000 femur is
      also consistent with this model. However, the two archaic H. sapiens juveniles
      show relatively small medullary cavities, possibly indicating a modified
      developmental pattern in this group. (2) Articulations follow a growth pattern
      similar to that of long-bone length (and stature), while cross-sectional
      diaphyseal dimensions (cortical area, second moments of area) show a contrasting
      growth pattern, with slower initial growth from childhood through mid
      adolescence, followed by a "catch-up" period that continues through early
      adulthood. This latter pattern is more similar to the growth curve for body
      weight, and may in fact partially reflect adaptation of the diaphysis to
      increased weight bearing. Because of these different growth patterns,
      articulations appear relatively large, and diaphyseal breadths relatively small
      during late childhood to mid-adolescence (i.e., about 9-13 years), when compared
      to adults from the same population. KNM-WT 15000 shows this same proportional
      difference from adult early Homo specimens, which is therefore interpreted as
      simply a developmental consequence of his age at death.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8141242
TI  - Four-million-year-old hominids from East Lake Turkana, Kenya.
AB  - A piece of mandible and several isolated teeth are reported from fluviatile
      sediments older than 4 million years at East Lake Turkana. They most closely
      resemble hominids from Laetoli, Tanzania and Hadar, Ethiopia which have been
      assigned to Australopithecus afarensis.

PMID- 8141243
TI  - Metatarsophalangeal joint function and positional behavior in Australopithecus
      afarensis.
AB  - Recent discussions of the pedal morphology of Australopithecus afarensis have led
      to conflicting interpretations of australopithecine locomotor behavior. We report
      the results of a study using computer aided design (CAD) software that provides a
      quantitative assessment of the functional morphology of australopithecine
      metatarsophalangeal joints. The sample includes A. afarensis, Homo sapiens, Pan
      troglodytes, Gorilla gorilla, and Pongo pygmaeus. Angular measurements of the
      articular surfaces relative to the long axes of the metatarsals and phalanges
      were taken to determine whether the articular surfaces are plantarly or dorsally
      oriented. Humans have the most dorsally oriented articular surfaces of the
      proximal pedal phalanges. This trait appears to be functionally associated with
      dorsiflexion during bipedal stride. Pongo has the most plantarly oriented
      articular surfaces of the proximal pedal phalanges, probably reflecting an
      emphasis on plantarflexion in arboreal positional behaviors, while the African
      hominoids are intermediate between Pongo and Homo for this characteristic. A.
      afarensis falls midway between the African apes and humans. Results from an
      analysis of metatarsal heads are inconclusive with regard to the functional
      morphology of A. afarensis. Overall, the results are consistent with other
      evidence indicating that A. afarensis was a capable climber.

PMID- 8141244
TI  - Vertebral arthritis and physical activities in the prehistoric southeastern
      United States.
AB  - Vertebral arthritis is examined in a prehistoric Native American sample from
      northwestern Alabama. Both osteophytosis (OP) of the vertebral bodies and
      osteoarthritis (OA) of the apophyseal facets are highest in the lumbar vertebrae,
      followed by the cervical and thoracic segments, although differences are much
      more striking in OP. OA is bilaterally asymmetric, with greater prevalence on the
      right side in the upper thoracic region. Much of the patterning seen in arthritis
      in this and other samples is due to the stresses imposed by spinal curvature and
      weight-bearing due to our erect posture. In addition, handedness is the probable
      cause of asymmetry in OA. However, the high levels of cervical OP are unexpected,
      and may be due to use of the tumpline in carrying burdens.

PMID- 8141245
TI  - Degrees of freedom in interspecific allometry: an adjustment for the effects of
      phylogenetic constraint.
AB  - The data used in studies of bivariate interspecific allometry usually violate the
      assumption of statistical independence. Although the traits of each species are
      commonly treated as independent, the expression of a trait among species within a
      genus may covary because of shared common ancestry. The same effect exists for
      genera within a family and so on up the phylogenetic hierarchy. Determining
      sample size by counting data points overestimates the effective sample size,
      which then leads to overestimating the degrees of freedom that should be used in
      calculating probabilities and confidence intervals. This results in an inflated
      Type 1 error rate. Although some workers (e.g., Felsenstein [1985] Am. Nat. 125:1
      15) have suggested that this issue may invalidate interspecific allometry as a
      comparative method, a correction for the problem can be approximated with
      variance components from a nested analysis of variance. Variance components
      partition the total variation in the data set among the levels of the nested
      hierarchy. If the variance component for each nested level is weighted by the
      number of groups at that level, the sum of these values is an estimate of an
      effective sample size for the data set which reflects the effects of phylogenetic
      constraint. Analysis of two data sets, using taxonomy to define levels of the
      nested hierarchy, suggests that it has been common for published studies of
      interspecific allometry to severely overestimate the number of degrees of
      freedom. Interspecific allometry remains an important comparative method for
      evaluating questions concerning individual species that are not similarly
      addressed by the format of most of the newer comparative methods. With the
      correction proposed here for estimating degrees of freedom, the major statistical
      weakness of the procedure is substantially reduced.

PMID- 8141246
TI  - The insulin receptor: structure, function, and signaling.
AB  - The insulin receptor is a member of the ligand-activated receptor and tyrosine
      kinase family of transmembrane signaling proteins that collectively are
      fundamentally important regulators of cell differentiation, growth, and
      metabolism. The insulin receptor has a number of unique physiological and
      biochemical properties that distinguish it from other members of this large well
      studied receptor family. The main physiological role of the insulin receptor
      appears to be metabolic regulation, whereas all other receptor tyrosine kinases
      are engaged in regulating cell growth and/or differentiation. Receptor tyrosine
      kinases are allosterically regulated by their cognate ligands and function as
      dimers. In all cases but the insulin receptor (and 2 closely related receptors),
      these dimers are noncovalent, but insulin receptors are covalently maintained as
      functional dimers by disulfide bonds. The initial response to the ligand is
      receptor autophosphorylation for all receptor tyrosine kinases. In most cases,
      this results in receptor association of effector molecules that have unique
      recognition domains for phosphotyrosine residues and whose binding to these
      results in a biological response. For the insulin receptor, this does not occur;
      rather, it phosphorylates a large substrate protein that, in turn, engages
      effector molecules. Possible reasons for these differences are discussed in this
      review. The chemistry of insulin is very well characterized because of possible
      therapeutic interventions in diabetes using insulin derivatives. This has allowed
      the synthesis of many insulin derivatives, and we review our recent exploitation
      of one such derivative to understand the biochemistry of the interaction of this
      ligand with the receptor and to dissect the complicated steps of ligand-induced
      insulin receptor autophosphorylation. We note possible future directions in the
      study of the insulin receptor and its intracellular signaling pathway(s).

PMID- 8141247
TI  - Muscarinic cholinergic receptor subtypes in rat sublingual glands.
AB  - Mucin glycoprotein secretion by rat sublingual glands is regulated primarily by
      muscarinic cholinergic receptors. Studies were conducted to identify muscarinic
      receptor subtypes in whole glands as well as in isolated acinar structures. In
      radioligand binding studies, we used subtype-selective antagonists in competition
      studies to initially determine receptor subtype heterogeneity. In membranes from
      whole glands, both pirenzepine and methoctramine displayed two affinity sites (M1
      and M3) of nearly equal proportions. In contrast, acinar membranes contained a
      1:2 and 2:1 ratio of M1 to M3 sites for pirenzepine and methoctramine,
      respectively. In all cases, p-fluoro-hexahydro-siladifenidol and 4
      diphenylacetoxy-N-methylpiperidine each bound to a single class of binding sites.
      Northern analysis using oligonucleotide probes specific for the 5' ends of the
      translated regions of m1 through m5 receptors detected only m1 and m3 subtypes in
      poly(A)+ RNA from whole glands. We also used antisera specific for each receptor
      subtype to immunoprecipitate solubilized receptors from membrane preparations.
      Only m1 (51.7 and 64.9%) and m3 (48.3 and 34.7%) subtypes were found consistently
      in membranes from whole sublingual glands and isolated acini, respectively.
      Studies with other exocrine glands generally described the predominance of m3
      receptors, and m1 receptors, if present, were presumably associated with
      contaminating neural structures. Our results therefore demonstrate that mucous
      acini from rat sublingual glands contain abundant amounts of both m1 and m3
      receptors.

PMID- 8141248
TI  - Identification of a sorbitol permease in human erythrocytes.
AB  - Sorbitol, a polyol derived from glucose by the enzyme, aldose reductase, is a
      common organic solute in many cells. It plays a role in the osmotic regulation of
      epithelial cells and in the pathology of uncontrolled diabetes. To learn more
      about sorbitol transport, we measured D-[14C]sorbitol influx in human
      erythrocytes. Sorbitol influx at 37 degrees C was a linear function of sorbitol
      concentration over the range of 0.05-100 mM. The activation energy for sorbitol
      influx was 10.0 kcal/mol, and the Q10 over the range 10-50 degrees C was 1.8,
      higher than predicted for diffusion through an aqueous pore. Glucose transport
      inhibitors either had no effect (1 mM phloridzin) or minimally inhibited
      (approximately 35% inhibition by 10 microM cytochalasin B or 250 microM
      phloretin) sorbitol influx. Influx was stimulated twofold by 0.5 mM p
      chloromercuribenzoic acid, an inhibitor of glucose transport, and this was
      reversed by 2 mM dithiothreitol. Sorbitol influx was neither Na dependent nor
      sensitive to changes in cell volume. Glucose, fructose, mannitol, myo-inositol,
      and gluconate, at four- to fivefold molar excesses over sorbitol, did not inhibit
      its influx. We conclude that there is a specific sorbitol transport pathway in
      human erythrocytes similar to the sorbitol permease in renal epithelial cells.

PMID- 8141249
TI  - Human rsk isoforms: cloning and characterization of tissue-specific expression.
AB  - Serine-threonine protein kinases in the ribosomal S6 kinase (rsk or p90rsk)
      family have been implicated as signaling intermediates in the cellular response
      to several growth factors. To investigate the molecular diversity of human p90rsk
      isoforms, mixed degenerate oligonucleotide polymerase chain reaction was used to
      isolate partial rsk cDNAs (1.1 kb). Three closely related human rsk cDNAs were
      obtained (HU-1, HU-2, HU-3). These cDNAs are encoded by separate genes based on
      DNA sequence diversity and distinct patterns seen with genomic Southern blots.
      Northern analysis revealed different sized mRNA transcripts for each isoform. A
      full-length HU-1 cDNA (3.1 kb) was subsequently isolated from a HeLa cell
      library. 5'-cDNA clones for HU-2 and HU-3 were isolated using the "rapid
      amplification of cDNA ends" strategy. Experiments using human x hamster somatic
      cell hybrids localized the HU-1 gene to human chromosome 3; HU-2 is on chromosome
      6; and HU-3 is on the X chromosome. The tissue distribution of human rsk mRNAs
      was determined using ribonuclease protection assays. HU-3 mRNA was present in
      multiple RNA samples. HU-2 was expressed in fibroblast > muscle > lymphocyte =
      placenta > liver. HU-1 was expressed in Epstein-Barr virus lymphocyte > > muscle
      = liver > fat = placenta. These results indicate that the multiplicity of p90rsk
      isoforms is increased to at least three for humans and that marked tissue-/cell
      specific differences in p90rsk isoform expression are present.

PMID- 8141250
TI  - Human kidney proximal tubules are the main source of plasma glutathione
      peroxidase.
AB  - The sites of synthesis of extracellular (E) glutathione peroxidase (GPX), a
      unique selenoglycoprotein present in plasma, are not known. To investigate the
      possibility that the kidney is the main source for the plasma GPX, we examined
      GPX activities and selenium concentrations in the plasma of patients with renal
      failure on dialysis and nephrectomized patients before and after kidney
      transplantation. Plasma GPX activities in these patients were 42, 22, and 180% of
      normal EGPX activity, respectively, whereas plasma Se levels were within the
      normal range. Twenty-four hours after nephrectomy of anesthetized rats, plasma
      GPX activity was 30.0 +/- 6.4% of the activity at zero time. Northern
      hybridization analysis of eight human tissues probed with EGPX and cellular
      glutathione peroxidase (CGPX) cDNA revealed that the ratio of EGPX to CGPX was
      highest in the kidney. cRNA in situ hybridization studies on kidney slices showed
      that only proximal tubular epithelial cells and parietal epithelial cells of
      Bowman's capsule contained EGPX transcripts. Caki-2, a proximal tubular renal
      carcinoma cell line, makes and actively secretes EGPX. Taken together, these
      results strongly suggest that kidney proximal tubular cells are the main source
      for GPX activity in the plasma.

PMID- 8141251
TI  - Soluble alpha v beta 3-integrin ligands raise [Ca2+]i in rat osteoclasts and
      mouse-derived osteoclast-like cells.
AB  - We evaluated the possible involvement of intracellular Ca2+ concentration
      ([Ca2+]i) changes in the action of alpha v beta 3-ligands, known to regulate
      osteoclast function. Rat osteoclasts or mouse osteoclast-like cells, as examined
      by microfluorimetry and fura 2, showed a transient [Ca2+]i increase when perfused
      with (all 0.1 microM) vitronectin, osteopontin, polypeptide echistatin,
      fibronectin, and Arg-Gly-Asp-Asp and Arg-Gly-Asp-Ser peptides (10(-4) M) but not
      with laminin, collagen I, collagen IV, or [Ala24]echistatin, in which Ala was
      substituted for Arg in the Arg-Gly-Asp complex. The threshold for echistatin was
      10 pM, the 50% effective concentration was 1 nM, and the median [Ca2+]i increase
      was 420 nM above the resting level (217 +/- 22 nM) at saturating concentration of
      0.1 microM. Echistatin did not cause Mn2+ influx, and 10 microM nifedipine, 10 nM
      omega-conotoxin, 5 mM Ni2+, or Cd2+ did not prevent [Ca2+]i change. However,
      extracellular Ca2+ was needed for the [Ca2+]i increase, probably enabling ligand
      integrin interaction. Polyclonal and monoclonal (LM609) antibody as well as
      depletion of [Ca2+]i stores with 5 microM thapsigargin and Ca(2+)-free medium
      abolished the [Ca2+]i increase, after restoring extracellular Ca2+. Furthermore,
      the LM609 antibody induced a Ca2+ signal in the presence or absence of
      extracellular Ca2+, suggesting that the alpha v beta 3-ligand interaction is
      mediated at least partially by Ca2+ mobilized from intracellular stores.

PMID- 8141252
TI  - Augmented expression of cytosolic phospholipase A2 during phenotypic
      transformation of cultured type II pneumocytes.
AB  - Over time in culture, rat type II alveolar epithelial cells (AEC) demonstrate
      increased levels of unesterified arachidonic acid (AA) and increased prostanoid
      synthesis, while assuming certain morphological and biochemical characteristics
      of the type I cell phenotype. The objective of this study was to elucidate the
      enzymatic mechanism(s) responsible for increased AA accumulation in this model.
      Cells were examined both early in culture (2 days), when they retained type II
      cell features, and later in culture (7 days), when they are known to express a
      number of type I cell characteristics. An increase in AA levels at day 7
      persisted despite inhibition of AA reacylation, suggesting that differences in
      deacylation were responsible for differences in free fatty acid levels. These
      differences in deacylation were not explained by differing susceptibilities to
      hydrolysis of radiolabeled endogenous lipids from day 2 and day 7 cells. The
      phospholipase A2 (PLA2) activities at both days in culture were qualitatively
      similar and typical of the recently described high-molecular-mass cytosolic PLA2
      (cPLA2), but activity in day 7 cytosol was threefold greater than that present in
      day 2 cytosol. A neutralizing anti-cPLA2 antibody reduced the PLA2 activity in
      day 7 cytosol to the level found in day 2 cytosol. Immunoblot analysis failed to
      detect expression of low-molecular-mass PLA2 proteins but confirmed that
      expression of the 97-kDa cPLA2 was greater in day 7 cytosol than in day 2
      cytosol. These results indicate that increased levels of unesterified AA in AEC
      with phenotype altered during culture are due to augmented steady-state
      expression of cPLA2 and suggest for the first time that expression of cPLA2 is
      differentiation dependent.

PMID- 8141253
TI  - Calcium-dependent halothane activation of sarcoplasmic reticulum calcium channels
      from frog skeletal muscle.
AB  - The effect of halothane on calcium channels present in sarcoplasmic reticulum
      membranes isolated from frog skeletal muscle was studied at the single channel
      level after fusing the isolated vesicles into planar lipid bilayers. Addition of
      91 microM halothane to the cytosolic compartment containing 1 microM free calcium
      activated the channel by increasing fractional open time from 0.11 to 0.59,
      without changing the channel conductance. The activation of the channels by
      halothane was calcium dependent. At resting calcium concentrations in the
      cytosolic compartment, halothane failed to activate the channel, whereas maximal
      activation was found at 10 microM calcium. The free energy of halothane binding
      to the channel decreased from -5.8 kcal/mol at 1 microM calcium to -6.6 kcal/mol
      at 10 microM calcium. Halothane increased the open time constants and decreased
      the closed time constants, indicating that it binds to both the open and the
      closed configurations of the channel.

PMID- 8141254
TI  - Calcium-dependent release of arachidonic acid in response to purinergic receptor
      activation in airway epithelium.
AB  - The effect of purinergic receptor agonists on arachidonic acid release was
      investigated in [3H]arachidonic acid-prelabeled human airway epithelial cells.
      Exposure of bronchial epithelial BEAS39 cells to extracellular ATP resulted in a
      marked release of unesterified [3H]arachidonic acid with maximal effect observed
      within 60-90 s. [3H]diacylglycerol and [3H]phosphatidic acid accumulated in
      parallel with [3H]arachidonic acid. ATP-stimulated [3H]arachidonic acid release
      with a K0.5 of 9 +/- 2 microM and UTP was equipotent; no effect was observed with
      P2Y- or P2X-purinergic receptor agonists or with adenosine. Similar results were
      obtained with primary cultures of normal human nasal epithelium, CF/T43 and HBE1
      airway epithelial cell lines derived from a cystic fibrosis patient and from a
      normal donor, respectively, and HT-29 human colon carcinoma cells. ATP stimulated
      inositol phosphate formation in BEAS39 cells with a concentration dependence
      identical to that for [3H]arachidonic acid release. The effect of ATP on both
      [3H]arachidonic acid release and inositol phosphate formation was equally
      inhibited by pertussis toxin. The Ca2+ ionophore A-23187 mimicked the effects of
      ATP or UTP on arachidonic acid release, and a marked inhibitory effect was
      observed with thapsigargin. The protein kinase C inhibitor staurosporine
      partially inhibited ATP-stimulated [3H]arachidonic acid release. These data are
      consistent with the hypothesis that phospholipase A2 activation is secondary to
      P2U-purinergic receptor stimulation of D-myoinositol 1,4,5-trisphosphate
      production and calcium mobilization from intracellular stores.

PMID- 8141255
TI  - Simultaneous measurement of intracellular Na+ and Ca2+ during K(+)-free perfusion
      in isolated myocytes.
AB  - To study the relationship between intracellular Na+ concentration ([Na+]i) and
      intracellular Ca2+ concentration ([Ca2+]i), guinea pig ventricular myocytes were
      loaded with both the Na(+)-sensitive probe, sodium-binding benzofuran
      isophthalate (SBFI), and the Ca(2+)-sensitive probe, fluo 3. [Na+]i was measured
      from the ratio image at 510 nm when excited at 340/380 nm. [Ca2+]i, expressed as
      the percent change of corrected fluo 3 fluorescence, was measured at 540 nm when
      excited at 500 nm. The fluorescent spectra of these probes were sufficiently
      different to allow for simultaneous measurement. After 30 min perfusion of K(+)
      free solution, [Na+]i of rod-shaped cells increased from 6.4 +/- 0.5 to 20.6 +/-
      2.6 mM, and [Ca2+]i increased to 256 +/- 36% of the control. [Ca2+]i was higher
      in spontaneously contracting cells and shortened cells than in rod-shaped cells
      at similar levels of [Na+]i. When Ca(2+)-free solution or Ni2+ (5 mM) was
      applied, [Ca2+]i was lower than in cells perfused with K(+)-free solution alone.
      It was suggested that extracellular Ca2+ and the Na(+)-Ca2+ exchange were
      involved in the increase in [Ca2+]i. In conclusion, we have developed a new
      method for the simultaneous measurement of [Na+]i and [Ca2+]i in isolated
      myocytes, which should be useful to study the relation between [Na+]i and
      [Ca2+]i.

PMID- 8141256
TI  - Aldosterone selectively increases Na(+)-K(+)-ATPase alpha 3-subunit mRNA
      expression in rat hippocampus.
AB  - In the brain, corticosteroids bind to intracellular glucocorticoid (GR) and
      mineralocorticoid (MR) receptors, affecting target gene transcription, and
      thereby altering neuronal function, including electrophysiological activity. The
      hippocampus very highly expresses both MR and GR; however, MR-regulated
      hippocampal transcripts have not yet been described. We investigated the effects
      of adrenalectomy +/- glucocorticoid or mineralocorticoid replacement on
      expression of mRNAs encoding alpha-subunit isoforms of Na(+)-K(+)
      adenosinetriphosphatase, a critical transmembrane ion gradient-regulating enzyme.
      Aldosterone significantly increased alpha 3-subunit mRNA expression in dentate
      gyrus granule cells (62% increase compared with adrenalectomy) and in CA1 and CA4
      hippocampal neurons (37 and 38%), but not in CA2, CA3, parietal cortex neurons,
      or glia. This effect was not reproduced by dexamethasone, and none of the
      corticosteroid manipulations altered alpha 1- or alpha 2-subunit mRNA expression
      at any site examined. Aldosterone-mediated upregulation of hippocampal alpha 3
      subunit mRNA expression may underlie, at least in part, the specific actions of
      MR ligands on hippocampal function. The observation that aldosterone
      differentially affects alpha 3-isoform mRNA expression in distinct neuronal
      populations, associated with the established aldosterone modulations of alpha 1
      isoform mRNA in epithelial cells, supports the presence of cell-specific factors
      that regulate MR-mediated transcriptional activity.

PMID- 8141257
TI  - Second messenger specificity of the inositol trisphosphate receptor: reappraisal
      based on novel inositol phosphates.
AB  - To further understand how the second messenger D-myo-inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] interacts with its intracellular receptor, we injected 47 highly
      purified inositol phosphate (InsP) positional isomers in Xenopus oocytes and
      compared their potency in releasing intracellular Ca2+. The potency of the Ca(2+)
      releasing InsPs spanned four orders of magnitude. Seven compounds, including the
      novel inositol 1,2,4,5-tetrakisphosphate [D/L-Ins (1,2,4,5)P4] and D/L
      Ins(1,4,6)P3, had a very high potency. All of these highly active InsPs shared
      the following structure: two D-trans-equatorial phosphates (eq-P) and one
      equatorial hydroxyl (eq-OH) attached to ring carbons D-4, D-5, and D-6 (or to the
      structurally equivalent D-1, D-6, and D-5 carbons). This permissive structure was
      not sufficient for Ca2+ release, because it was also found in two inactive
      compounds, Ins(1,6)P2 and Ins(1,3,6)P3. To be active, InsPs also required the
      structural equivalent of a D-3 eq-OH and/or a D-1 eq-P. Together, our data reveal
      how the structure of the InsP molecule affects its ability to release Ca2+.

PMID- 8141258
TI  - BDM affects nucleotide binding and force generation steps of the cross-bridge
      cycle in rabbit psoas muscle fibers.
AB  - The effect of 2,3-butanedione monoxime (BDM) on elementary steps of the cross
      bridge cycle was studied with the sinusoidal analysis technique in skinned rabbit
      psoas muscle fibers. Our results showed that isometric tension and stiffness
      decreased progressively with an increase in the BDM concentration. The MgATP and
      MgADP binding constants increased 27 and 6 times, respectively, when BDM was
      increased from 0 to 18 mM, whereas the phosphate binding constant did not change
      significantly. The equilibrium constants of the ATP isomerization and detachment
      step were not sensitive to BDM, whereas the equilibrium constant of the
      attachment (power stroke) step decreased with BDM. Thus, in the presence of BDM,
      the number of attached cross bridges decreases; more cross bridges accumulate in
      the detached state, causing isometric tension and stiffness to decline. However,
      our detailed analysis shows that the decrease in the number of attached cross
      bridges is approximately 40%, which is not adequate to account for the 84%
      decrease in the isometric tension when 18 mM BDM was present. Therefore we
      suggest that a thin-filament activation mechanism is also affected by BDM.

PMID- 8141259
TI  - Thrombin receptor activation peptide induces pulmonary vasoconstriction.
AB  - We investigated the involvement of the 14-residue thrombin receptor activating
      peptide SFLLRNPNDKYEPF (TRAP-14) in mediating the pulmonary vasoconstriction in
      response to alpha-thrombin. Isolated guinea pig lungs were uniformly perfused
      with Ringer-albumin solution at a constant flow of 28 ml/min. Addition of TRAP-14
      or human alpha-thrombin to the perfusate caused dose-dependent increases of
      pulmonary arterial pressure within 1 min. TRAP-14 at 1 microM increased pulmonary
      arterial pressure to a similar extent as 10 nM alpha-thrombin (i.e., increase of
      7.7 +/- 0.8 and 7.4 +/- 0.9 cmH2(0) from baseline, respectively). The increases
      in pulmonary venous resistance induced by TRAP-14 and alpha-thrombin were two- to
      fivefold greater than the increases in pulmonary arterial resistance, indicating
      that both agonists mediated pulmonary hypertension secondary to pulmonary
      venoconstriction. Stimulation of cultured guinea pig pulmonary artery smooth
      muscle cells with 100 microM TRAP-14 or 10 nM alpha-thrombin increased cytosolic
      Ca2+ concentration about five- to sevenfold over baseline. The increase in
      cytosolic Ca2+ concentration in smooth muscle cells was not observed with a
      subsequent challenge with either agonist, indicating desensitization. In the
      perfused lungs, an initial stimulation with alpha-thrombin or TRAP-14
      desensitized the lungs to either agonist. The alpha-thrombin-desensitized lungs
      remained refractile to alpha-thrombin after 1 h of perfusion with fresh Ringer
      solution, whereas the TRAP-14-desensitized lungs recovered 79% of the
      vasoconstrictor response by 10 min and 93% of the response by 30 min.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141260
TI  - Multiphasic control of proteolysis by leucine and alanine in the isolated rat
      hepatocyte.
AB  - Autophagically mediated proteolysis in the perfused rat liver is under complex
      multiphasic control by a small group of amino acids dominated by leucine. Because
      there have been no prior reports of such regulation in the isolated hepatocyte,
      our goal was to determine whether it is a manifestation of interactions between
      diverse cells in the intact liver or, alternatively, the expression of a unique
      control mechanism within a single population of cells. Hepatocytes were isolated
      from livers of ad libitum-fed rats and incubated with cycloheximide at low
      density (approximately 10(6) cells/ml) for the determination of valine release.
      As in perfusion experiments with synchronously fed rats, proteolytic responses to
      leucine in cells from fed rats were mediated through two inhibitory mechanisms
      that alternated randomly on a day-to-day basis. The first (L) represented a
      typical multiphasic dose-response with low- and high-concentration inhibition
      separated by a sharp zonal loss of inhibition that could be abolished by alanine.
      The second (H) mediated inhibition only at high concentrations. It disappeared
      after 24 h of starvation, leaving L as the prevailing mode. The findings indicate
      that both macroautophagy and the multiphasic mechanism for regulating it coexist
      in a single population of hepatocytes, making the cells suitable for studies
      aimed at defining the putative plasma membrane site of leucine recognition.

PMID- 8141261
TI  - High-affinity [3H]PN200-110 and [3H]ryanodine binding to rabbit and frog skeletal
      muscle.
AB  - In vertebrate skeletal muscle, the voltage-dependent mechanism of sarcoplasmic
      reticulum (SR) Ca2+ release, commonly referred to as excitation-contraction (E-C)
      coupling, is mediated by the voltage-sensing dihydropyridine receptor (DHPR),
      which is believed to affect SR Ca2+ release through a physical interaction with
      the SR ryanodine receptor (RYR)/Ca2+ release channel. Scatchard analysis of
      ligand binding of [3H]PN200-110 to the DHPR and [3H]ryanodine to the RYR
      indicated the presence of high-affinity sites in muscle homogenates, with maximum
      binding (Bmax) values of 72 +/- 26 and 76 +/- 30 pmol/g wet wt for rabbit
      skeletal muscle, and 27 +/- 14 and 44 +/- 13 pmol/g wet wt for frog skeletal
      muscle, respectively. The Bmax values corresponded to a PN200-110-to-ryanodine
      binding ratio of 0.98 +/- 0.26 and 0.61 +/- 0.24 for rabbit and frog skeletal
      muscle, respectively, and were found by Student's t test to be significantly
      different (P < 0.02, n = 7). These results are compared with measurements with
      isolated rabbit skeletal muscle membrane fractions and discussed in relation to
      our current understanding of the mechanism of E-C coupling in skeletal muscle.

PMID- 8141262
TI  - Characterization of cochlear outer hair cell turgor.
AB  - The cochlear outer hair cell (OHC) is a cylindrical cell with structural features
      suggestive of a hydraulic skeleton, i.e., an elastic shell with a positive
      internal pressure. This study characterizes the role of the OHC elevated
      cytoplasmic pressure in maintaining the cell shape. Intracellular pressure of
      OHCs from guinea pig is estimated by measuring changes in cell morphology in
      response to increasing or decreasing osmolarity. Cells collapse when subjected to
      a continuous increase in osmolarity. Collapse occurs at an average of 8 mosM
      above the standard medium, suggesting that normal cells have an effective
      intracellular pressure of 128 mmHg. Fewer cells collapse when exposed to slow
      rates of osmolarity increase than cells exposed to fast rates of osmolarity
      increase, although the final change in osmolarity in the perfusion chamber is
      similar. Furthermore, cells undergo a slow, spontaneous increase in volume on
      exposure to either no osmolarity change or slow rates of osmolarity increase,
      suggesting that the cell's internal osmolarity increases in vitro. After volume
      reduction or elevation, cells do not return to their initial volume.

PMID- 8141263
TI  - Intracellular pH recovery during respiratory acidosis in perfused hearts.
AB  - Na(+)-H+ exchange and Na(+)-dependent HCO3- influx both contribute to recovery of
      intracellular pH (pHi) after an acidosis induced by using the NH4Cl prepulse
      technique in mammalian and avian cardiac tissue. We have investigated the
      relative contributions of these mechanisms to pHi recovery during respiratory
      acidosis in the Langendorff-perfused ferret heart with and without correction of
      extracellular pH (pHo). pHi was measured from the chemical shift of the exogenous
      31P nuclear magnetic resonance pH indicator 2-deoxy-D-glucose 6-phosphate.
      Intrinsic intracellular buffering capacity, calculated from the change in
      intracellular HCO3- concentration after a change in CO2, was reduced from
      approximately 33 (no inhibitors of acid extrusion present) to 19 +/- 5 mM when H+
      extrusion during the acid loading phase was inhibited. During respiratory
      acidosis (pHo approximately 6.95), the proton efflux rate (JH) calculated at pHi
      6.85 was 0.30 +/- 0.04 mmol.l-1.min-1 (n = 9). When pHo was corrected by
      increasing external HCO3- concentration to 60 mM during respiratory acidosis (pHo
      approximately 7.33), JH was 1.11 +/- 0.11 mmol.l-1.min-1 (n = 7), and when pHo
      was partially corrected by the addition of 50 mM N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid to the perfusion solution (pHo approximately 7.1), JH was
      0.64 +/- 0.08 mmol.l-1.min-1 (n = 6). In all three groups Na(+)-H+ exchange and
      HCO3- influx each contributed approximately 50% to acid-equivalent
      efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141264
TI  - Low pH enhances expression of carbonic anhydrase II by cultured rat inner
      medullary collecting duct cells.
AB  - Carbonic anhydrase (CA) facilitates the secretion of protons from renal epithelia
      by catalyzing the buffering of hydroxyl ions by CO2. We have previously found
      that inner medullary collecting duct (IMCD) cells cultured from rat kidney
      secrete protons and express CA II. Incubation of IMCD cells in acidic medium for
      48 h has been shown to stimulate the secretion of protons by a protein synthesis
      dependent process. To establish whether CA II might be involved in this process,
      IMCD cells were exposed to incubation media supplemented with 10(-7) M
      deoxycorticosterone acetate, pH 7.0 (acid) or pH 7.7 (control) for 48 h, and CA
      II mRNA and protein were quantitated. Part of the CA II cDNA was obtained by
      reverse transcription of total RNA from rat kidney followed by amplification
      using oligonucleotide primers derived from conserved areas in the coding regions
      of human, mouse, and chick CA II cDNAs in a polymerase chain reaction. By
      Northern analysis, steady-state levels of CA II mRNA from acid-incubated cells
      showed an increase of 80% compared with controls and 70% when expressed relative
      to a housekeeping mRNA, beta-actin. Western blot analysis using a human antibody
      to CA II showed an approximate doubling of CA II protein after acid incubation.
      By immunofluorescence microscopy, the domes of acid-incubated IMCD cells
      contained considerably more CA II-stained cells than found in control cultures.
      Thus incubation of IMCD cells in acid medium stimulates the expression of CA II
      mRNA and protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141265
TI  - Cell volume and K+ transport during differentiation of mouse erythroleukemia
      cells.
AB  - In the present study, we evaluated the changes in cell volume, water content, and
      K+ transport in mouse erythroleukemia (MEL) cells during the transition from
      proerythroblast to young reticulocyte. When MEL cells were exposed to 1.8%
      dimethyl sulfoxide (DMSO) for a maximum of 7 days, they synthesized hemoglobin
      and reduced their volume by 66% while maintaining their water content. The total
      protein content decreased by 50%. We therefore concluded that the volume
      reduction was due to a loss of cellular material, water, and osmolytes. To
      evaluate the changes in pump and leak pathways, we performed 86Rb uptakes in the
      presence or absence of selected inhibitors. In undifferentiated cells, the uptake
      was mainly represented by the Na-K-2Cl cotransport (51%) and by the Na(+)-K+ pump
      (34%). A small portion of the uptake was mediated by barium- and quinidine
      sensitive K+ channels (8%) and by the furosemide-sensitive K-Cl cotransporter
      (5%). After 4 days in DMSO, the 86Rb uptake was reduced by 57%, mainly due to a
      substantial (90%) decrease in Na-K-2Cl cotransport activity. The Na(+)
      independent K-Cl cotransport activity also dramatically decreased by a factor of
      10. In contrast, the Na(+)-K+ pump activity did not change after 4 days in DMSO.
      These results demonstrate a marked reduction in the activities of inorganic ion
      cotransport systems as red blood cells differentiate to reticulocytes. Our study
      also demonstrates that a strong correlation exists between cell volume reduction
      and a decrease in the main inward leak pathway for K+: the Na-K-2Cl
      cotransporter.

PMID- 8141266
TI  - Effects of insulin and exercise on amino acid transport in rat skeletal muscle.
AB  - In the present study, the initial rates of amino acid transport by isolated rat
      skeletal muscle plasma membrane vesicles were investigated. This approach
      facilitates the study of the transport of naturally occurring amino acids
      independent of the effects of cellular metabolism. Alanine and glutamine influxes
      were measured using a rapid filtration technique. Transport was examined in the
      presence and absence of Na and the properties of membranes from control, insulin
      treated, or acutely exercised rats were studied. Both alanine and glutamine were
      transported by Na-dependent processes. The values for maximum rate of transport
      (Vmax) for Na-dependent alanine and glutamine transport were 203 and 224 pmol.mg
      1.s-1, respectively. The K1/2 values were 2.9 mM alanine and 1.9 mM glutamine.
      The Vmax for Na-dependent alanine transport was increased by insulin treatment of
      the animal and by acute exercise. 2-(Methylamino)-isobutyric acid (MeAIB)
      partially inhibited the control Na-dependent alanine influx and completely
      inhibited the increase due to insulin or exercise treatment, indicating the
      importance of both system A and a non-system A, Na-dependent carrier for alanine
      transport. The Vmax for Na-dependent MeAIB uptake was also increased by insulin
      or exercise treatments of the rats. Unlike alanine, Na-dependent glutamine
      transport was not affected by insulin.

PMID- 8141267
TI  - Regulation of NaCl entry into Necturus gallbladder epithelium by protein kinase
      C.
AB  - The role of protein kinase C in the regulation of the mode of NaCl entry into
      Necturus gallbladder epithelial cells was determined from the rate and magnitude
      of ouabain-induced cell swelling in the presence of inhibitors. Stimulation of
      protein kinase C by phorbol ester increased the rate of cell swelling from the
      control value of 2.9% to 4.7%/min and caused the predominant apical membrane
      transport mechanism for NaCl to switch from bumetanide-sensitive Na-Cl
      cotransport to amiloride-sensitive parallel exchange. Na-Cl cotransport could be
      restored as the predominant mode of NaCl entry by treatment of stimulated tissues
      with the kinase inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7)
      and calphostin C. Therefore the mechanism of NaCl transport across the apical
      membrane can be controlled by the activity of protein kinase C.

PMID- 8141268
TI  - Cl- current activation in choroid plexus epithelial cells involves a G protein
      and protein kinase A.
AB  - The involvement of GTP-binding proteins (G proteins) in the regulation of the Cl-
      conductance in rat choroid plexus epithelial cells was investigated, using the
      whole cell patch-clamp technique. Intracellular application of a nonhydrolyzable
      GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 0.1-0.2 mM),
      evoked a transient increase in the Cl- conductance. The activated Cl- current
      exhibited inward rectification and was independent of time at hyperpolarizing or
      depolarizing voltage pulses. The effect of GTP gamma S was inhibited by a
      nonhydrolyzable GDP analogue, guanosine 5'-O-(2-thiodiphosphate) (2 mM), and by
      an inhibitor of protein kinase A, H-89, but was not affected by chelation of
      cytosolic Ca2+ with 5 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid. GTP gamma S failed to activate the current when ATP was omitted from the
      pipette solution. Intracellular application of adenosine 3',5'-cyclic
      monophosphate (cAMP; 0.25 mM) or the catalytic subunit of protein kinase A
      activated a similar Cl- current. These results suggest that G proteins activate
      Cl- channels via a cAMP-dependent pathway in rat choroid plexus.

PMID- 8141269
TI  - 19F-NMR study of primary human T lymphocyte activation: effects of mitogen on
      intracellular pH.
AB  - Intracellular pH of purified human T lymphocytes was studied using nuclear
      magnetic resonance (NMR) spectroscopy under physiological conditions. In this
      paper we introduce a new improved 19F-NMR pH probe, 2-amino-3,3'
      difluoroisobutyric acid (vic-difluoro-alpha-methylalanine), which has a pKa of
      approximately 7.0, sensitivity of 0.83 ppm/pH, is noncytotoxic, and provides
      better signal-to-noise ratio for intracellular pH determinations. Quiescent and
      stimulated lymphocytes display different homeostatic intracellular pH values.
      Quiescent cells maintain intracellular pH of 7.04 +/- 0.03 at extracellular pH
      values between 6.9 and 7.3, and stimulated cells maintain intracellular pH of
      7.25 +/- 0.05 at extracellular pH values between 7.0 and 7.5. Stimulation with
      ionomycin plus phorbol 12-myristate 13-acetate leads to intracellular
      alkalinization within 90 min, reaching the more alkaline steady-state value of
      7.25 within 7-10 h. Proliferation, but not viability, of lymphocytes is dependent
      on extracellular pH in the range of 6.4-8.0, and this dependence is not due to
      limiting interleukin-2 elaboration. The mechanisms of pH regulation and the
      possible implications of a permissive pH for T lymphocyte proliferation are
      discussed.

PMID- 8141270
TI  - Aldosterone stimulates K secretion prior to onset of Na absorption in guinea pig
      distal colon.
AB  - Distal colon from guinea pig was stimulated in vitro by aldosterone in Ussing
      chambers that allowed measurement of short-circuit current (Isc) and tissue
      conductance (Gt). The response to aldosterone was delayed by approximately 20 min
      and resulted in a negative Isc, consistent with K secretion. Approximately 1 h
      later the Isc began to increase and eventually became positive, consistent with
      subsequent stimulation of Na absorption. The Na-absorptive response could be
      inhibited by mucosal amiloride without altering the rate of K secretion.
      Similarly, K secretion could be inhibited by serosal bumetanide without altering
      Na absorption. In the presence of spironolactone, actinomycin D, or
      cycloheximide, aldosterone failed to stimulate both K secretion and Na
      absorption. A dose response to aldosterone provided an apparent Kd of 2.6 +/- 0.5
      nM, consistent with a high-affinity receptor coupled to this secretory response.
      Stimulation by the K secretagogue epinephrine did not produce an additive
      increase in K secretion, suggesting that the same cell type responds to both
      aldosterone and epinephrine and that the protein induced by aldosterone was not
      one of the membrane proteins responsible for K secretion.

PMID- 8141271
TI  - Immunolocalization of anion exchanger AE2 and cation exchanger NHE-1 in distinct
      adjacent cells of gastric mucosa.
AB  - The gastric mucosa secretes both protons and bicarbonate. The molecular identity
      of the H(+)-K(+)-ATPase, which mediates acid secretion, has long been known, but
      the other components of the secretory machinery and their cellular disposition
      are less well characterized. This study identifies and localizes in rat and
      rabbit gastric mucosa a chloride-bicarbonate exchanger protein and a Na(+)-H+
      exchanger protein. The previously described band 3-related protein of the
      parietal cell has been identified by isoform-specific antibodies as anion
      exchanger (AE) 2 and localized to the basolateral membranes of the parietal
      cells. The Na(+)-H+ exchanger protein NHE-1 was located in the basolateral
      membranes of the mucous neck cells, interdigitated between the parietal cells of
      the gastric glands and in the basolateral membranes of the surface mucous cells.
      Neither transporter protein was abundantly expressed deep in the gland, where
      most of the pepsinogen cells reside. Carbonic anhydrase II (CA II) was expressed
      at higher abundance in the surface mucous cells and mucous neck cells, which
      expressed NHE-1, than in the parietal cells, which expressed AE2. The
      morphological evidence identified AE2 as a major parietal cell anion exchanger,
      whereas NHE-1 and CA II colocalized in mucous neck, chief, and surface mucous
      cells. We propose that all three of these cell types contribute to gastric
      bicarbonate secretion.

PMID- 8141272
TI  - Changes in lipolytic sensitivity following repeated epinephrine infusion in
      humans.
AB  - The lipolytic response to epinephrine is increased in lean but not obese subjects
      during conditions of increased circulating catecholamines such as starvation and
      critical illness. We evaluated the effect of repeated epinephrine treatment (0.03
      micrograms.kg-1.min-1 for 30 min thrice daily) on basal lipolysis and the
      lipolytic response to epinephrine in lean and obese subjects. Lipolytic rates
      were determined using [2H5]glycerol during basal conditions and 60 min of
      epinephrine infusion before and after 6 days of repeated epinephrine treatment.
      Basal lipolysis and the lipolytic response to epinephrine were higher in obese
      (2.47 +/- 0.51 mumol.kg-1.min-1 and 106 +/- 21 mumol/kg, respectively) than lean
      (1.45 +/- 0.15 mumol.kg-1.min-1 and 70 +/- 12 mumol/kg, respectively; P = 0.08
      obese vs. lean) subjects. Repeated epinephrine treatment decreased basal glycerol
      rate of appearance and the lipolytic response to epinephrine in lean and obese
      subjects. Plasma insulin concentration increased after repeated epinephrine
      treatment in both obese (14.3 +/- 0.6 to 18.2 +/- 1.6 microU/ml; P < 0.05) and
      lean (8.4 +/- 1.3 to 11.1 +/- 1.5 microU/ml; P < 0.01) subjects. Repeated
      epinephrine treatment suppresses basal and epinephrine-stimulated lipolysis.
      Increased plasma insulin concentration may be the mechanism.

PMID- 8141273
TI  - Glucose-induced thermogenesis in tetraplegic patients with low sympathoadrenal
      activity.
AB  - The influence of the sympathoadrenal system on the thermic effect of glucose was
      examined by studying six tetraplegic patients with complete lesions of the
      cervical spinal cord. Indirect calorimetry and catheter techniques were employed,
      and measurements were made before and during 2 h after oral ingestion of 75 g of
      glucose. The results were compared with previous findings from an identical study
      in healthy subjects and with those from a control group of five tetraplegic
      patients receiving water instead of glucose. In response to glucose, energy
      expenditure rose from 69 +/- 5 to 79 +/- 5 and from 88 +/- 3 to 98 +/- 4 W, (not
      significant) in the patients and healthy subjects, respectively. In both patients
      and the healthy subjects the postprandial oxygen consumption increased
      exclusively in extrasplanchnic tissues. Splanchnic blood flow, which in normals
      increased 34 +/- 1%, did not change in the patients after glucose. Blood
      temperatures were unchanged in normals after glucose but rose by approximately
      0.5 degrees C in the patients. The patients' arterial plasma concentrations of
      norepinephrine were low in the basal state and did not rise significantly after
      glucose. The arterial blood glucose concentrations after glucose were
      significantly higher in the patients than in the healthy subjects. Insulin levels
      rose to 105 +/- 20 mU/l in the patients and to 59 +/- 7 mU/l in the controls (P <
      0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141274
TI  - Rat skeletal muscle hexokinase II mRNA and activity are increased by a single
      bout of acute exercise.
AB  - This study addresses the potential role of skeletal muscle hexokinase (HK) II in
      the regulation of glucose uptake and metabolism in vivo. Male rats undertook a
      single bout of treadmill exercise and were then killed immediately or after a
      predetermined recovery period. Three muscles [soleus (Sol),
      gastrocnemius/plantaris (Gc), and white vastus] were excised, and HK II mRNA,
      GLUT-4 mRNA, total HK (HK I and HK II) and heat-stable HK (predominantly HK I)
      activities were assessed. Three hours after the cessation of a single bout of
      exhaustive exercise, HK II mRNA was significantly increased in all three muscles.
      Ninety or thirty minutes of exercise, with a 3-h recovery, increased Gc HK II
      mRNA to the same extent as exhaustive exercise, but 15 min of exercise had no
      effect. Gc HK II mRNA continued to increase up to 8 h after the cessation of 90
      min of exercise but returned to basal by 24 h postexercise. In contrast to HK II
      mRNA, Gc GLUT-4 mRNA was unchanged at 0, 3, 8, and 24 h after the cessation of 90
      min of exercise. Total HK activity was significantly increased in Sol and Gc, 8
      and 24 h after the cessation of 90 min of exercise. Heat-stable HK activity was
      unchanged in all three muscles. The increase in total HK activity, inferred to be
      an increase of HK II, may be important in the persistence of the postexercise
      increase in insulin action.

PMID- 8141275
TI  - Regulation of hormone-sensitive lipase during fasting.
AB  - Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. The
      activity of HSL is thought to be primarily regulated by phosphorylation
      dephosphorylation reactions. Although FFA levels are elevated during fasting, it
      has been difficult to demonstrate an increase in HSL activity with fasting. The
      current studies were undertaken to explore directly the regulation of HSL
      expression in adipose tissue in the rat during fasting. Rats were fasted for
      periods up to 5 days and HSL activity, HSL immunoreactive protein, and HSL mRNA
      levels were measured both in intact epididymal adipose tissue and in isolated
      adipose cells. Fasting caused a progressive decline in total body weight and the
      weight of epididymal fat pads, whereas adipose cell size decreased approximately
      50% after 2 days of fasting. Serum FFA levels approximately doubled within 1 day
      of fasting and remained elevated thereafter. Basal lipolysis, measured as
      glycerol release, did not increase until 2 days of fasting. HSL activity remained
      relatively unchanged until 3 days of fasting when it was increased twofold after
      3-5 days of fasting. Likewise, HSL immunoreactive protein and HSL mRNA levels
      increased twofold after 3-5 days of fasting. Thus HSL activity appears to be
      regulated by pretranslational mechanisms during prolonged fasting. However,
      increases in FFA flux during short-term fasting appear to involve either post
      translational control of HSL or the regulation of other enzymes.

PMID- 8141276
TI  - Contraction-induced increase in muscle insulin sensitivity: requirement for a
      serum factor.
AB  - The insulin sensitivity of glucose transport is enhanced in skeletal muscle after
      a bout of exercise. In a previous study, stimulation of washed muscles to
      contract in vitro, in contrast to exercise, did not result in an increase in
      insulin sensitivity. The purpose of the present study was to explain this
      apparent discrepancy. We found that, although rat epitrochlearis muscles
      stimulated to contract in vitro after 15 min of incubation in Krebs-Henseleit
      buffer did not develop increased insulin sensitivity, muscles stimulated to
      contract immediately after being dissected showed a small but significant
      enhancement of the stimulation of 3-O-methyl-D-glucose transport by 30 microU/ml
      insulin. Furthermore, muscles stimulated to contract in situ and then allowed to
      recover in vitro showed as large an increase in insulin sensitivity as that which
      occurs after a bout of swimming. To follow up these findings suggesting
      involvement of a humoral factor, we incubated epitrochlearis muscles in serum
      before and during contractile activity in vitro. Epitrochlearis muscle insulin
      sensitivity was enhanced to as great an extent after in vitro contractile
      activity in serum as after swimming. Experiments involving charcoal treatment,
      ultrafiltration, or trypsin digestion provided evidence that the serum factor
      that interacts with contractions to enhance insulin sensitivity is a protein.

PMID- 8141277
TI  - Regulation of eukaryotic initiation factor-2 expression during sepsis.
AB  - Protein synthesis is stimulated at the level of peptide chain initiation in
      livers from rats with a sterile or septic abscess. In contrast, peptide chain
      initiation is inhibited in fast-twitch skeletal muscles from septic rats. We
      investigated the possible mechanisms responsible for these differential changes
      in peptide chain initiation between liver and skeletal muscle during sepsis by
      measuring the cellular content of eukaryotic initiation factor-2 (eIF-2), the
      extent of phosphorylation of the alpha-subunit of eIF-2, and the activity of eIF
      2B. In skeletal muscle, neither the eIF-2 content nor the extent of
      phosphorylation of eIF-2 alpha was altered during sepsis. However, a significant
      decrease (P < 0.001) in eIF-2B activity was observed in fast-twitch muscles. In
      liver, neither the extent of phosphorylation of eIF-2 alpha nor the activity of
      eIF-2B was different in rats with a sterile or septic abscess compared with
      control. However, the amount of eIF-2 in liver was increased in both sterile
      inflammation and sepsis. The relative abundance of eIF-2 alpha mRNA was not
      increased in either condition compared with control. Analysis of the distribution
      of eIF-2 alpha mRNA from control rats revealed that only approximately 40% of the
      message was associated with polysomes. Sterile inflammation or sepsis caused a
      50% increase in the proportion of eIF-2 alpha mRNA associated with the polysomes
      compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141278
TI  - Effects of selective disruption of cytoskeletal elements on steroid secretion by
      human adrenocortical slices.
AB  - The role of the cytoskeleton in corticosteroid secretion in normal human adrenal
      gland was investigated in vitro, using the perifusion technique and confocal
      laser scanning microscopy. Vinblastine, which selectively disrupted microtubules
      in adrenocortical cells, did not modify the basal release of cortisol but induced
      a 58% inhibition of the response to adrenocorticotropic hormone (ACTH). In
      contrast, vinblastine did not alter dibutyryl adenosine 3',5'-cyclic
      monophosphate (DBcAMP)-induced steroid secretion. Cytochalasin B treatment caused
      disappearance of microfilaments and blocked the stimulatory action of ACTH and
      DBcAMP on cortisol secretion. beta,beta'-Iminodipropionitrile disorganized the
      cytokeratin intermediate filaments but did not alter spontaneous and ACTH-evoked
      cortisol release. These results, which provide the first evidence for an action
      of cytoskeleton inhibitors on cortisol release from normal human adrenocortical
      cells, show that microtubules are involved in the mechanism of action of ACTH at
      a step preceding adenosine 3',5'-cyclic monophosphate formation, whereas
      microfilaments are involved in a late and common step of adrenal steroidogenesis.

PMID- 8141279
TI  - Growth hormone treatment of obese women for 5 wk: effect on body composition and
      adipose tissue LPL activity.
AB  - Because it has been found that growth hormone (GH) treatment of GH-deficient
      adults is able to reduce the total fat mass, the present study was undertaken to
      investigate the effect of GH treatment in obese subjects. The investigation was a
      double-blind placebo-controlled crossover study in which nine obese females were
      treated with GH (0.03 mg.kg ideal body wt-1.day-1) and placebo for 5 wk. Body
      composition was determined by dual-energy X-ray absorptiometry, and the quantity
      of intra-abdominal adipose tissue was determined by CT scan. Lipoprotein lipase
      (LPL) activity was determined in fat biopsies taken from the subcutaneous
      abdominal and gluteal region. GH treatment significantly reduced the total fat
      mass from 40.5 to 38.4 kg (i.e., 5% reduction of the total fat mass; P < 0.01),
      whereas the fat-free mass increased from 50.5 to 53.5 kg (P < 0.01). In addition,
      GH treatment significantly reduced the intra-abdominal adipose tissue determined
      by CT scan (reduction by 7 +/- 0.3%; P < 0.02). CT scan performed at the level of
      the femur showed a 7% reduction in adipose tissue and a 5% increase in muscle
      volume in the GH group (P < 0.05). Thus no clear regional differences in the GH
      mediated reduction of the adipose tissue mass were observed. GH reduced the LPL
      activity by approximately 50% (P < 0.01) in the adipose tissue. Finally, GH
      treatment significantly increased the level of plasma free fatty acids (P <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141280
TI  - Vasopressin V1 and V2 receptors in diabetes mellitus.
AB  - Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin
      (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may
      contribute to the polyuria through diminished V2 receptor-mediated free water
      retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic
      rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared
      with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc,
      daily) partially lowered these values (P < 0.01). There was a reduction in the
      number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin
      animals compared with the sham animals (P < 0.05). The receptor affinity remained
      unchanged. In parallel, there was a reduction in maximum AVP-activated total
      inositol phosphate production in the liver and kidney of the diabetic and
      diabetic+insulin animals compared with the sham animals (P < 0.05). The density
      and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic
      monophosphate production in the diabetic and diabetic+insulin animals were
      unchanged compared with the sham. These results demonstrate differential
      regulation of AVP receptors and suggest that downregulation of renal V2 receptors
      does not contribute to the polyuria of diabetes. In contrast, downregulation of
      V1 receptors might contribute to diminished V1 receptor-mediated biological
      responses to AVP seen in diabetes mellitus.

PMID- 8141281
TI  - Effect of renal nerves on expression of renin and angiotensinogen genes in rat
      kidneys.
AB  - In this study, we try to determine the influence of renal nerve activity on renal
      function, plasma renin activity (PRA), and the corresponding expression of renin
      and angiotensinogen genes in the kidney. In pentobarbitone-anesthetized rats, the
      left renal nerves were stimulated (15 V, 0.2 ms) at frequencies to reduce left
      renal blood flow by 15, 30, and 45%. There were corresponding reductions in
      glomerular filtration rate from 12 to 52% and absolute and fractional sodium
      excretions from 20 to 75%. PRA levels in control rats were 10.8 +/- 1.5 and were
      increased to 65.9 +/- 9.1, 144.2 +/- 19.7, and 277.2 +/- 22.0 ng angiotensin I.h
      1.ml-1 after 1 h at each of the three levels of nerve stimulation. Renal renin
      mRNA was similar in innervated and denervated kidneys and was not affected by the
      lowest level of nerve stimulation; however, neurally induced decreases in blood
      flow to 30 and 45% increased renin mRNA levels by 3.0- and 3.4-fold (both P <
      0.05), respectively. Angiotensinogen mRNA levels were higher (P < 0.05) in
      kidneys subjected to the lowest level of nerve stimulation, but when renal blood
      flow was reduced by 30 and 45%, expression of this gene was unchanged.
      Stimulation of the renal nerves in the presence of the beta 1-adrenoceptor
      antagonist atenolol only doubled PRA at the highest rates of stimulation. Neither
      renal renin nor angiotensinogen mRNA were changed during neurally mediated
      reductions in renal blood flow of 15 or 30% after administration of
      atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141282
TI  - Acute noradrenergic activation induces insulin resistance in human skeletal
      muscle.
AB  - We assessed in normal subjects the effects of an acute increase in forearm
      norepinephrine (NE) release, evoked by -20 mmHg lower body negative pressure
      (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects
      underwent the following two insulin euglycemic clamps in random sequence: one
      during application of LBNP and the other without LBNP (control study). In the
      control study, hyperinsulinemia (approximately 60 microU/ml) produced a
      significant increment in forearm NE release, measured by using the forearm
      perfusion technique combined with infusion of tritiated NE (from 4.91 +/- 1 to
      7.94 +/- 1.33 ng.l-1.min-1; P < 0.05). Forearm glucose uptake rose from 0.97 +/-
      0.13 to 5.2 +/- 0.2 mg.l-1.min-1 in response to insulin infusion. When the
      insulin clamp was performed during LBNP, forearm NE release rose to significantly
      higher values than those of the control study (from 4.33 +/- 0.52 to 12.7 +/-
      1.46 ng.l-1.min-1; P < 0.01 vs. control). Under these conditions, the stimulatory
      effect of insulin on forearm glucose uptake was markedly reduced (from 0.78 +/-
      0.10 to 3.2 +/- 0.7 mg.l-1.min-1; P < 0.02 vs. control). Forearm blood flow and
      plasma epinephrine and free fatty acid concentrations were comparable in the two
      study sessions. These data demonstrate that an acute activation of endogenous NE
      release antagonizes insulin-mediated glucose uptake in forearm skeletal muscle,
      probably accounted for by a direct metabolic effect of NE.

PMID- 8141283
TI  - Skeletal muscle blood flow independently modulates insulin-mediated glucose
      uptake.
AB  - Insulin-mediated glucose uptake (IMGU) occurs principally in skeletal muscle. To
      directly examine whether skeletal muscle perfusion (F) can directly and
      independently modulate IMGU, we combined the hyperinsulinemic euglycemic clamp
      and leg balance techniques [leg glucose uptake (LGU) = arteriovenous glucose
      difference (delta AVG) x F]. Young (< 40 yr) healthy lean subjects were studied
      during euglycemic hyperinsulinemia of approximately 23 microU/ml (group I, n = 8)
      and approximately 950 microU/ml (group II, n = 6). Femoral delta AVG and leg F
      were measured, and LGU was calculated at baseline after approximately 200 min of
      steady-state hyperinsulinemia alone and during a superimposed intrafemoral artery
      infusion of methacholine hydrochloride designed to increase leg F two- to
      threefold. In groups I and II, insulin raised the delta AVG approximately 4- and
      14-fold, respectively (P < 0.0001). Leg F was unchanged during the low-dose
      insulin infusion (group I) but increased 112 +/- 35% in group II (P < 0.001).
      During methacholine infusion the delta AVG narrowed 35.9 +/- 6.8% (P < 0.01) and
      20.5 +/- 4.8% (P < 0.05) in groups I and II, respectively. Leg F rose 224 +/- 30%
      (P < 0.01) and 79 +/- 13% (P < 0.05) above the flow rate achieved with insulin
      alone. Thus, during methacholine flow modulation, LGU increased 116 +/- 36% (P <
      0.01) and 47 +/- 11% (P < 0.05) in groups I and II, respectively. In conclusion,
      skeletal muscle perfusion during hyperinsulinemia can act as an independent
      determinant of IMGU.

PMID- 8141284
TI  - Effect of chronic energy deprivation on cardiac thyroid hormone receptor and
      myosin isoform expression.
AB  - Thyroid hormone (3,5,3'-triiodothyronine; T3) and its receptor (TR) play an
      important regulatory role for in vivo and in vitro cardiac myosin heavy chain
      (MHC) isoform gene expression by activating the alpha- and inhibiting the beta
      MHC genes. Previous studies have shown that chronic energy deprivation (CED; 50%
      of normal caloric intake) in the rat impacts cardiac MHC protein expression and
      hemodynamic parameters in a pattern typically seen with hypothyroidism; yet,
      unlike hypothyroidism, circulating T3 levels are not depressed. Therefore, the
      goal of this study was to determine if the altered MHC isoform expression
      observed in CED is associated with altered TR expression, both at the mRNA and
      protein levels. Female rats weighing approximately 250 g were allocated into two
      groups, designated as normal control (NC) and CED. After 5 wk, the relative
      content of alpha-MHC protein and mRNA levels decreased in CED ventricles by 20%
      (P < 0.05). In contrast, the relative content of both beta-MHC protein and mRNA
      levels increased five- to sixfold in CED (P < 0.05). Although there were no
      changes in TR mRNA levels relative to 18S rRNA in CED, the total number of
      nuclear TRs decreased 3.5-fold in the CED group (P < 0.05), from a maximum
      binding capacity of 840 +/- 130 fmol/mg DNA in NC to 241 +/- 118 fmol/mg DNA in
      CED, with no change in the affinity of the receptor.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8141285
TI  - Plasma vitamin C affects glucose homeostasis in healthy subjects and in non
      insulin-dependent diabetics.
AB  - In aged healthy (n = 10) and non-insulin-dependent (type II) diabetic (n = 10)
      subjects matched for age [67.3 +/- 0.5 vs. 68.0 +/- 0.4 yr, P = not significant
      (NS)], body mass index (25.7 +/- 0.7 vs. 26.0 +/- 0.2 kg/m2, P = NS), gender
      ratio [6 males (M)/4 females (F) vs. 5 M/5 F], and mean arterial blood pressure
      (104 +/- 6 vs. 105 +/- 9 mmHg, P = NS), we determined the changes in insulin
      secretion and action after vitamin C infusion and the relative increase in plasma
      vitamin C levels. At the highest vitamin C infusion rate (0.9 mmol/min) the
      increase in plasma vitamin C levels did not affect B cell response to glucose,
      but it improved Conard's K values and whole body glucose disposal in healthy
      subjects and in diabetic patients. In both groups of subjects vitamin C-mediated
      increase in insulin action was mainly due to an improvement in nonoxidative
      glucose metabolism. After fasting, plasma vitamin C levels correlated with basal
      whole body glucose disposal (r = -0.44, P < 0.05; n = 20). After vitamin C
      infusion, percent change in plasma vitamin C level correlated with the percent
      decline in membrane microviscosity (r = 0.53, P < 0.01; n = 20) and increase in
      whole body glucose disposal (r = 0.63, P < 0.003; n = 20). In conclusion, plasma
      vitamin C levels seem to play a role in the modulation of insulin action in aged
      healthy and diabetic subjects.

PMID- 8141286
TI  - 11 beta-Hydroxysteroid dehydrogenase in the rat inner ear.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) was demonstrated specifically
      in the spiral ligament of the cochlear membranous labyrinth by enzyme assay,
      Western blotting, and immunocytochemistry. Other cochlear regions and the
      vestibular membranous labyrinth were devoid of 11 beta-HSD. Spiral ligament 11
      beta-HSD exerted predominantly an oxidative activity and was NADP specific, which
      is similar to 11 beta-HSD in most other tissues. 11 beta-HSD was colocalized with
      mineralocorticoid and glucocorticoid steroid receptors in the spiral ligament. 11
      beta-HSD may control steroid binding to these inner ear steroid receptors and, in
      addition, may regulate steroid receptor binding in the adjacent stria vascularis
      in paracrine fashion.

PMID- 8141287
TI  - Effects of LHRH and ANG II on prolactin stimulation are mediated by hypophysial
      AT1 receptor subtype.
AB  - We have used the nonpeptide angiotensin II (ANG II) receptor antagonists losartan
      (receptor subtype AT1) and PD-123319 (AT2) to determine the participation of ANG
      II receptor subtypes in luteinizing hormone-releasing hormone (LHRH)-induced
      prolactin release in a perifusion study using intact pituitaries in vitro. LHRH
      (1.85 x 10(-7) M) released prolactin consistently, whereas losartan (10(-5) M)
      abolished prolactin response without modifying basal prolactin or luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH) release. PD-123319 (10(-5) M)
      had no effect on basal or LHRH-induced prolactin, LH, or FSH release. We also
      determined that the effect of ANG II on prolactin release was mediated by the
      same receptor subtype. In adenohypophysial cells dispersed in vitro ANG II (10(
      8) M) released prolactin. Losartan (10(-7) and 10(-6) M), but not PD-123319,
      inhibited this effect. We conclude that in intact hypophyses of 15-day-old female
      rats the effect of LHRH on prolactin release is readily demonstrated. LHRH
      induced prolactin release appears to be mediated by ANG II acting in a paracrine
      manner on AT1 receptors located on lactotrophs.

PMID- 8141288
TI  - Reliability of error estimates from the minimal model: implications for
      measurements in physiological studies.
AB  - MINMOD provides an estimate of the error in the insulin sensitivity index (SI)
      and glucose effectiveness at basal insulin (Sg) as the fractional standard
      deviation (FSD). The validity of the FSD estimate has not been assessed in a
      large number of human studies, nor has a comparison of the accuracies achievable
      using the two different intravenous glucose tolerance test (IVGTT) protocols
      (glucose only and tolbutamide protocol) been performed. To address these two
      issues, we obtained the FSD value and performed Monte Carlo simulations for 237
      IVGTT studies. The FSD underestimated the true error as determined as the
      coefficient of variation from Monte Carlo simulation (COV-MC) with the ratio of
      COV-MC to FSD being 3.07 +/- 0.20 (mean +/- SE) for SI using the tolbutamide
      protocol. Additionally, the mean COV-MC for glucose-only protocol was
      approximately two to three times that for the tolbutamide protocol for both SI
      and Sg. We conclude that FSD underestimates the true error in SI and Sg.
      Additionally, more accurate results are obtained from the tolbutamide protocol
      than with the glucose-only protocol.

PMID- 8141289
TI  - Neuroimmune signaling in regulation of intestinal ion transport.
AB  - Complex interactions between the enteric nervous system, the immune system, and
      the epithelium govern the transport rates of salt and water across the intestinal
      lining. Luminal antigens or bacterial products are detected by the immune system,
      which triggers a cascade of events associated with the release of inflammatory
      mediators. These mediators, by lowering the response threshold for transmission
      in some neural circuits, augment ongoing neural reflexes that promote secretion.
      Associated with these effects is a dampening of responses in other neural
      circuits innervating the mucosal effectors. Selective excitation and inhibition
      of the neural reflex circuitry coupled with direct actions of inflammatory
      mediators on epithelial cells result in stereotypical motility and secretory
      patterns that are characterized by strong muscular contractions, copious
      secretion, and diarrhea.

PMID- 8141290
TI  - Transport of bovine serum albumin across rat jejunum: role of the enteric nervous
      system.
AB  - To assess the mechanisms for movement of antigenically intact macromolecules
      across small intestinal mucosa, transport kinetics of bovine serum albumin (BSA)
      uptake and the effect of neural and metabolic inhibition were examined in
      stripped short-circuited rat jejunum. The mucosa was exposed to BSA, and, after a
      50-min equilibration, mucosal-to-serosal movement of immunologically intact BSA
      was determined by enzyme-linked immunosorbent assay and total BSA by radiolabeled
      125I-BSA. Intact BSA uptake demonstrated saturable kinetics. Immunologically
      intact BSA crossed the intestinal mucosa as 4.5% of total 125I-BSA flux.
      Colchicine and 4 degrees C significantly reduced uptake of immunologically intact
      BSA. NaF significantly reduced uptake of immunologically intact BSA and 125I-BSA.
      Treatment with tetrodotoxin significantly reduced intact BSA uptake, but did not
      significantly alter total BSA uptake. The muscarinic cholinoceptor antagonist
      atropine also significantly inhibited transport of intact BSA, whereas the
      nicotinic cholinoceptor antagonist hexamethonium had no effect. These findings
      indicate that transport of intact macromolecules across small intestinal mucosa
      is a saturable energy-dependent process that utilizes the microtubular network
      and is regulated by the enteric nervous system primarily through cholinergic
      nerves acting on muscarinic receptors.

PMID- 8141291
TI  - Effects of prostaglandins on gastrin release from canine antral mucosal cells in
      primary culture.
AB  - Evidence in vivo indicates that endogenous and exogenous prostaglandins can alter
      gastrin secretion. We have used primary cultures containing canine antral G-cells
      to study the cellular actions of prostaglandins on gastrin secretion, comparing
      the effects of prostaglandin E2 (PGE2) and its synthetic analogue enprostil.
      Enprostil (10(-10)-10(-6) M) inhibited gastrin secretion in response to bombesin,
      carbachol, and forskolin, the latter a receptor-independent activator of
      adenylate cyclase. This inhibition by enprostil was reversed by treatment with
      pertussis toxin (200 ng/ml, 8 h). However, enprostil did not inhibit the
      postreceptor stimuli 8-bromoadenosine 3',5'-cyclic monophosphate (10(-3) M),
      calcium ionophore A-23187 (10(-7) M), or 4 beta-phorbol 12-myristate 13-acetate
      (10(-8) M). In contrast, whereas PGE2 inhibited forskolin-stimulated gastrin
      release, PGE2 did not inhibit the response to carbachol or bombesin in control
      cultures. However, in pertussis toxin-treated cultures, PGE2 inhibition was
      reversed and, in contrast, the responses to bombesin, carbachol, and possibly
      forskolin were augmented. Indomethacin at a dose of 10(-5) M did not alter basal
      or bombesin-stimulated gastrin secretion. However, the somatostatin antibody CURE
      S6 enhanced the response to forskolin and enhanced inhibition by PGE2, suggesting
      that endogenous somatostatin produced an inhibitory tone in these cultures and
      excluding the possibility that PGE2 acted via release of endogenous somatostatin.
      Our data suggest that in cultured antral cells gastrin release is regulated by
      inhibitory and stimulatory prostaglandin mechanisms.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8141292
TI  - Adrenal secretion of BAM-22P, a potent opioid peptide, is enhanced in rats with
      acute cholestasis.
AB  - The adrenal gland is known to produce and release endogenous opioids into the
      circulation. Bovine adrenal medulla docosapeptide (BAM-22P) is a potent opioid
      agonist, derived from the proenkephalin A gene, which is present in the adrenal
      medulla. This study was undertaken to determine whether BAM-22P is released into
      plasma during acute cholestatic liver injury, which increases plasma total opioid
      activity. Acute cholestasis was induced by bile duct ligation or administration
      of the hepatotoxin alpha-naphthylisothiocyanate. Plasma levels of BAM-22P were
      determined by a sensitive radioimmunoassay, and the specificity of the assay was
      confirmed using high-performance liquid chromatography. Plasma BAM-22P levels was
      cholestatic rats were significantly higher than those in control rats. This
      increase in plasma BAM-22P levels was completely prevented by adrenalectomy.
      Adrenal steady-state levels of proenkephalin mRNA, as determined by Northern blot
      hybridization analyses, were also increased significantly in cholestatic rats.
      These increases in proenkephalin mRNA levels were not paralleled by changes in
      adrenal BAM-22P peptide levels, which were similar in cholestatic rats and their
      respective controls. Similar levels of proenkephalin mRNA expression were
      observed in innervated and denervated adrenal glands from cholestatic rats,
      suggesting that the increase in adrenal proenkephalin mRNA levels in acute
      cholestasis is not due to splanchnic nerve activation. Thus acute cholestasis in
      the rat is associated with adrenal secretion and accumulation in plasma of the
      highly potent opioid peptide BAM-22P and an augmentation of adrenal proenkephalin
      mRNA expression. The increase in plasma BAM-22P levels may contribute
      substantially to the increase in total circulating opioid activity documented in
      cholestatic rats.

PMID- 8141293
TI  - Role of nitric oxide in neurally induced pancreatic exocrine secretion in pigs.
AB  - Formation of NO, enzymatically catalyzed by NO synthases in both endothelial
      cells and autonomic nerves, seems to explain some noncholinergic nonadrenergic
      tissue reactions. We studied the possible role of NO in vagally induced
      pancreatic exocrine secretion using isolated perfused porcine pancreas (n = 11)
      with intact vagus nerve (VN) supply. Electrical stimulation of the VN (8 Hz, 10
      mA) and infusions of vasoactive intestinal polypeptide (VIP, 2 x 10(-9) M) were
      carried out before and after addition to the perfusate of the NO synthase
      inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or NG-nitro-L
      arginine (L-NNA, 10(-5) M) with and without further addition of L-arginine (10(
      3) M). We also studied the effects of L-arginine alone and of sodium
      nitroprusside (10(-4) M). In all experiments VN and VIP caused a profuse exocrine
      secretion (43 +/- 7 and 44 +/- 11 times basal secretion). The inhibitors
      increased vascular resistance approximately twofold but had no effect on the
      vascular relaxation caused by VIP and VN. The exocrine fluid response to VN was
      reduced to 19 +/- 5 and 4.7 +/- 1.8% (L-NAME and L-NNA), and response to VIP was
      reduced to 54 +/- 12 and 35 +/- 13%. Protein and bicarbonate outputs largely
      paralleled flow rate. Addition of L-arginine (no effects alone) to L-NAME
      restored the responses to VN (to 100 +/- 21% of controls) and increased VIP
      responses (to 65 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141294
TI  - Reversible disassembly of an intestinal epithelial monolayer by prolonged
      exposure to phorbol ester.
AB  - This article describes a model of reversible disassembly of a cultured human
      intestinal epithelial monolayer by prolonged exposure to the phorbol ester 12-O
      tetradecanoylphorbol 13-acetate (TPA). Prolonged phorbol ester exposure reduces
      protein kinase C (PKC) levels in numerous cell types including T84, as shown
      here. Under PKC-downregulated conditions, T84 monolayers, which simulate the
      highly organized structure of native intestinal crypt cells, become disassembled
      into 2 or 3 layers of rounded cells. Proliferation does not account for these
      morphological changes as assessed by thymidine incorporation studies. The effects
      of structural disorganization on epithelial barrier function was also examined.
      The permeability of disassembled monolayers was significantly greater than that
      of controls. Flux studies localized the permeability defect to the tight
      junction. PKC-associated alterations in the perijunctional ring of actin and
      myosin, one of the putative regulators of flow across the tight junction, were
      found to correlate with the observed functional changes. Most interesting was the
      fact that monolayer reassembly to the original columnar epithelial phenotype and
      reestablishment of barrier function occurred upon normalization of PKC levels.
      This model of reversible monolayer disassembly will allow investigation into the
      relationship between epithelial structure and function and examination of factors
      that govern monolayer formation.

PMID- 8141295
TI  - Nitric oxide synthesis inhibition increases epithelial permeability via mast
      cells.
AB  - In this study, we assessed the involvement of mast cells and mast cell-derived
      mediators in the enhanced epithelial permeability associated with nitric oxide
      synthesis inhibition. Permeability of the small bowel was assessed by measuring
      the clearance of a small marker (51Cr-labeled EDTA) from blood to lumen in the
      presence of the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl
      ester (L-NAME). L-NAME caused a very rapid (10 min) increase in epithelial
      permeability, reaching peak values (sixfold increase) within 20 min. Two mast
      cell stabilizers, doxantrazole and lodoxamide, greatly attenuated the rise in
      mucosal permeability. Rat mast cell protease II activity (marker of mucosal mast
      cell degranulation) was increased significantly only in the plasma of L-NAME
      treated animals. Chronic dexamethasone administration depleted rats of mucosal
      mast cells and also prevented the L-NAME-induced rise in mucosal permeability.
      The increase in epithelial permeability was mediated by a number of mediators:
      platelet-activating factor caused the early rise in epithelial permeability, and
      histamine caused the later increase in epithelial permeability. Superoxide
      dismutase attenuated the L-NAME-induced rise in epithelial permeability,
      suggesting an important and continuous role for superoxide. Transepithelial flux
      of 51Cr-EDTA across rat intestinal epithelial cell monolayers did not increase in
      the presence of L-NAME, suggesting that inhibition of nitric oxide does not
      directly cause epithelial permeability alterations, whereas the in vivo data
      implicate a potential role for the mast cell. In conclusion, nitric oxide
      synthesis inhibition activates mast cells in the mucosa and consequently
      increases epithelial permeability.

PMID- 8141296
TI  - 5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic
      transmission in enteric neurons.
AB  - The actions of 5-hydroxtryptamine (5-HT)1A and 5-HT4 receptor agonists on fast
      excitatory postsynaptic potentials (EPSPs) in myenteric neurons of guinea pig
      ileum were studied in vitro. Intracellular electrophysiological methods were used
      to record EPSPs. 5-HT (0.1 microM), 5-carboxamidotryptamine (0.001-0.1 microM), 8
      hydroxydipropylaminotetralin (0.003-0.3 microM), and 5-methoxytryptamine (5-MeOT;
      0.3 microM) inhibited EPSPs. Agonist inhibition of EPSPs was blocked by the 5
      HT1A receptor antagonists, spiperone and NAN-190. In the presence of NAN-190 (0.3
      microM), 5-HT (0.001-0.1 microM) increased EPSP amplitude. 5-MeOT (0.001-0.1
      microM), renzapride (0.01-0.3 microM), cisapride (0.01-1 microM), and BIMU 8
      (0.003-0.1 microM) increased EPSP amplitude but did not change the membrane
      potential of any neuron. EPSP potentiation induced by each agonist was blocked by
      the 5-HT3/5-HT4 receptor antagonist, tropisetron (1 microM), but not by the 5-HT3
      receptor antagonist, ondansetron (1 microM). Potentiation of fast EPSPs by 5-HT
      (0.1 microM) desensitized, whereas renzapride (0.1 microM) responses did not.
      Desensitization induced by BIMU 8 was variable. These data indicate that enteric
      5-HT1A and 5-HT4 receptors function to inhibit and facilitate transmitter
      release, respectively. 5-HT4-mediated facilitation of ganglionic
      neurotransmission could contribute to the prokinetic effects of cisapride and
      renzapride.

PMID- 8141297
TI  - Role of leukocytes in indomethacin-induced small bowel injury in the rat.
AB  - This study assesses the role of neutrophils in indomethacin-induced small bowel
      injury and determines the influence of intestinal pH on the magnitude of this
      injury. Rat jejunum was perfused via the lumen with buffer, and mucosal injury
      was assessed by blood-to-lumen clearance of 51Cr-EDTA and quantitative histology.
      Reduction in luminal pH from 7.4 to 6.0 in the presence of indomethacin (1.0
      mg/ml) increased 51Cr-EDTA clearance from 2.0 +/- 0.1 to 6.5 +/- 0.3
      microliter.min-1.g-1. Indomethacin caused a reduction in villus length, an
      increase in villus width, and an increase in lesion score. Depletion of
      neutrophils with antiserum largely prevented the increase in 51Cr-EDTA clearance
      and morphological changes. Intravenous indomethacin given at a dose to mimic
      therapeutic plasma levels (1 mg/kg iv) had no significant effect on 51Cr-EDTA
      clearance but caused similar morphological changes to those observed following
      intraluminal administration. The data suggest that neutrophils play a role in
      acute indomethacin injury and that the drug given intravenously can cause
      morphological changes without necessarily altering mucosal permeability to 51Cr
      EDTA.

PMID- 8141298
TI  - Oxidative stress induces S-thiolation of specific proteins in cultured gastric
      mucosal cells.
AB  - Oxidative stress induces the formation of protein-mixed disulfides with low
      molecular-weight thiols, especially glutathione. We analyzed this process, termed
      S-thiolation, in cultured gastric mucosal cells from guinea pigs by gel
      electrophoresis and autoradiography after radiolabeling of the intracellular
      glutathione pool with 35S. Hydrogen peroxide (H2O2) or diamide initiated rapid
      and reversible S-thiolation of specific proteins with molecular masses of 42, 30,
      29, 28, and 22 kDa. Diamide caused particularly prominent S-thiolation of the 42
      kDa protein. This protein was identified as actin by immunoblot analysis and
      actin-myosin precipitation. Fluorescence microscopy revealed that diamide caused
      a disappearance of normal stress fibers and a concomitant increase in actin
      polymerization in association with contraction of the cells. These morphological
      changes were completely reversible within minutes. With cells depleted of
      glutathione by incubation with DL-buthionine-[S,R]-sulfoximine, diamide caused
      severe contraction and rounding, and the cells detached from the culture plates.
      S-thiolation of actin could help protect gastric mucosal cells against
      irreversible organization of microfilaments by preserving microfilament dynamics
      under oxidative stress.

PMID- 8141299
TI  - Intrinsic corporoantropyloric coordination of motility and gastric emptying.
AB  - This study examined changes in gastric motility after interruption of the
      intramural nervous circuitry from the proximal portion of the stomach to the
      antrum by a circumferential gastric myotomy. Seven extraluminal strain gauge
      force transducers and five platinum electrodes were implanted along the
      antropyloroduodenal region, and gastric emptying was studied by X-ray after a 280
      g solid meat meal mixed with barium. The motility index increased aboral to the
      myotomy by 106 and 69% in the distal antrum and pylorus, respectively, in the
      first postprandial 30-60 min because of the loss of an inhibitory neural
      influence from the proximal part of the stomach. Destabilization of the basic
      electrical rhythm occurred in 50% of the dogs. This was apparent as
      tachyarrhythmia or bradyarrhythmia and an early postprandial 2-11% decrease in
      slow-wave frequency and a 100% increase in slow-wave amplitude. Coordination of
      corporoantropyloric contractions was disorganized. Frequent segmenting and
      antidromic contractions were associated with reduced periods of optimal emptying
      and disturbed intragastric chyme transport into the constricted antrum. A 10-30%
      gastric emptying delay of approximately 50 min was a consequence of myotomy
      despite an increased antroduodenal motor gradient after myotomy. The overall
      results suggest that intact intramural innervation and muscular continuity are
      essential for coordination of corporoantropyloric motility and normal gastric
      emptying.

PMID- 8141300
TI  - Gastric epithelial damage induced by local ischemia-reperfusion with or without
      exogenous acid.
AB  - We evaluated the damage to the gastric epithelium produced by local ischemia
      reperfusion (IR) with or without luminal perfusion with 0.1 N HCl. Local gastric
      ischemia was induced by clamping the left gastric artery. Use of radioactive
      microsphere technique revealed a significant reduction in blood flow induced only
      in the corpus (67% reduction). Because no measurable gross lesion was observed in
      this model, the blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served
      as an index of epithelial damage. In the absence of exogenous acid, the
      histological damage was minimum and could not be quantified. However, a
      significant increase in 51Cr-EDTA clearance was observed shortly after
      reperfusion in a manner that depended on the duration of ischemia. This increase
      in clearance reached a maximum approximately 10 min after reperfusion and
      returned rapidly toward control levels within 40-50 min after reperfusion. In the
      presence of exogenous acid, EDTA clearance increased significantly during
      ischemia, increased further during reperfusion, and did not recover for at least
      60 min after reperfusion. The acid infused after reperfusion (no acid before
      reperfusion) did not significantly aggravate the mucosal damage that followed
      reperfusion. However, the acid infused before reperfusion (no acid after
      reperfusion) showed an effect on EDTA clearance similar to that induced by
      continuous acid perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141301
TI  - Rheogenic Cl- conductance and Cl(-)-Cl(-)-exchange activities in guinea pig
      jejunal basolateral membrane vesicles.
AB  - We describe a method for the simultaneous purification of apical (brush-border
      membrane) and basolateral membrane (BLM) vesicles from the same sample of guinea
      pig jejunum. We applied functional tests to demonstrate the absence of reciprocal
      cross contamination between the two vesicle preparations. By using the BLM
      vesicles and a rapid filtration technique, we quantified 36Cl uptake under
      conditions of equilibrated pH (pHout = pHin = 7.5). The presence of 200 mM cis of
      either Na+ or K+, or an equimolar mixture of both, significantly increased the
      initial Cl- entry rate. In the presence of K+, valinomycin further increased Cl-
      uptake, but no Cl- uphill transport was ever observed under any of the
      conditions. All the increases were abolished by voltage clamping, indicating that
      the alkali-metal ions act by creating an inside-positive membrane potential
      capable of stimulating a Cl(-)-conductance pathway. In the absence of K+, BLM
      vesicle preloading to obtain a [Cl-]out/[Cl-]in = 16/200 mM gradient (delta Cl-)
      resulted in a 500% increase in the initial 36Cl- entry rate, accompanied by a
      transient Cl- accumulation, with an overshoot at approximately 5 min. In the
      presence of both a positive-inside electrical gradient (delta psi) and a delta Cl
      , the initial Cl- uptake rate was increased by 800%, indicating that the effects
      of delta psi and of delta Cl- are additive. The delta Cl- effect was blocked, but
      only partially, by short-circuiting the membrane potential with equilibrated K+
      and valinomycin, thus indicating that it has both rheogenic and electroneutral
      components. We conclude that Cl- influx across the guinea pig intestinal BLM
      involves a Cl(-)-conductance pathway plus a distinct Cl(-)-Cl(-)-exchange system,
      exhibiting both electroneutral and rheogenic components. Alternatively, the
      possibility can also be entertained that the conductance and the exchange
      pathways share a common molecular basis, e.g., a nonobligatory Cl(-)-Cl-
      exchanger or rheogenic uniport.

PMID- 8141302
TI  - Plasma membrane order parameter in periportal and perivenular hepatocytes
      isolated from ethanol-treated rats.
AB  - Hepatic ethanol (EtOH) metabolism has been assumed to involve hepatocytes
      differently, according to their location in the hepatic acinus. This study's aim
      was to gain information on plasma membrane (PM) order parameter in periportal
      (PP) and perivenular (PV) hepatocyte-enriched fractions isolated by a digitonin
      collagenase perfusion technique from rats pair-fed for 6-8 wk liquid diets
      containing either EtOH or isocaloric carbohydrates. Fluorescence polarization (P)
      studies have been performed to measure PM order parameter of PP and PV
      hepatocytes cultured for 2-6 h on glass cover slips and labeled with 1-[4
      (trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), a specific probe for
      PM of living cells. Fluorescence polarization and microscopy indicated that TMA
      DPH is a suitable probe to study PM order parameter in subconfluent rat
      hepatocyte monolayers where it labeled, after a rapid incorporation, PM of cells.
      In pair-fed control rats, PM order parameter was lower in PP hepatocytes than in
      PV cells (P = 0.366 +/- 0.013 vs. 0.381 +/- 0.021, respectively, P < 0.02; n =
      7). In EtOH-treated rats, these zonal differences tended to disappear (P = 0.419
      +/- 0.012 in PP cells vs. 0.417 +/- 0.007 in PV cells; n = 7). In addition, the
      order parameter was significantly higher either in PP or PV hepatocytes compared
      with pair-fed control animals (P < 0.002 and 0.003, respectively). A 30-min
      culture of cells in the presence of 40-200 mM EtOH significantly decreased the PM
      order parameter of hepatocytes isolated from pair-fed control rats with respect
      to EtOH-treated animals both in PP and PV cells (P < 0.01 and 0.02, respectively;
      n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141303
TI  - Effect of brefeldin A on lymphatic triacylglycerol transport in the rat.
AB  - Brefeldin A (BFA) has been shown in in vitro studies to either collapse the Golgi
      into the endoplasmic reticulum (ER) or the peripheral organelles into the trans
      Golgi network. Our goal was to determine the effect of BFA on intestinal lipid
      transport, since the Golgi is thought to play an important role in this process
      and simultaneously establish the effectiveness of BFA in an in vivo system. We
      infused rats intraduodenally with glyceryl tri-[3H]oleate at 135 mumol/h for 15 h
      and included BFA, 750 micrograms/h, during hours 4-7 of infusion. Mass and lipid
      disintegrations per minute output into the lymph fell to 9% of input rates at 8 h
      of infusion and returned to steady-state values at 12 h of infusion. Both
      chylomicron and very low-density lipoprotein output were severely affected by the
      BFA. Electron microscopy showed that the Golgi was collapsed into the ER. Mucosal
      triacylglycerol (TG) mass and disintegrations per minute were increased at 7 h of
      infusion in BFA infused rats vs. controls in the proximal half of the intestine.
      Lipid absorption, lipase activity, and mucosal TG synthesis were normal in the
      BFA-treated rats. We conclude that BFA works in vivo and in the intestine
      collapses the Golgi into the ER. As a consequence, lymphatic TG transport was
      severely affected.

PMID- 8141304
TI  - Phosphoramidon attenuates big endothelin-1-induced vasoconstriction in canine
      stomach.
AB  - We compared the effects of endothelin-1 and its precursor, big endothelin-1, on
      vascular resistance of a blood-perfused ex vivo stomach segment of chloralose
      anesthetized dogs. In separate groups of dogs, endothelin-1 or big endothelin-1
      was infused intra-arterially directly to the gastric segment. Endothelin-1 caused
      statistically significant dose-related increases in gastric vascular resistance
      at final blood concentrations of 0.15-10 nM. Although each dose was given for
      only 5 min, endothelin-1 at concentrations > 0.6 nM caused sustained responses
      with vascular resistance remaining above control values for approximately 45-90
      min. In contrast, however, big endothelin-1 caused a small but statistically
      significant vasoconstriction only at the highest concentration (10 nM). In other
      experiments, using 15-min peptide infusions, we found that pretreatment with
      phosphoramidon, an inhibitor of endothelin-converting enzyme, markedly reduced
      response to big endothelin-1 but not to endothelin-1. Our results demonstrate
      that endothelin-1, but not big endothelin-1, is a potent vasoconstrictor of the
      canine gastric microcirculation. In addition, it appears that big endothelin-1 is
      degraded to endothelin-1 in the stomach by a phosphoramidon-sensitive
      metalloproteinase.

PMID- 8141305
TI  - Evidence that bile salts are important for iron absorption.
AB  - The role of bile salts in intestinal Fe absorption has not previously been
      defined. We have recently shown that bile salts having cholanic ring 7 alpha-OH
      and/or 12 alpha-OH groups bind Fe2+ with high affinity at premicellar
      concentrations and also produce a two-to threefold enhancement in Fe2+ uptake
      from perfused intestinal segments in vivo. However, the physiological relevance
      of these observations for Fe2+ absorption was not known. To study this, we
      examined the effects of a single dose of taurocholate (TC) administered with 59Fe
      FeSO4 in reversing iron malabsorption induced by bile duct ligation. Fe
      absorption from three 0.5-mg doses of 59Fe-FeSO4 was measured from five groups of
      six adult Sprague-Dawley rats each: group 1, before and after bile duct ligation
      and subsequent administration of 59Fe-FeSO4 + TC test dose; group 2, before and
      after bile duct ligation followed by a third dose of Fe alone; group 3, before
      and after bile duct ligation followed by a third dose of Fe+taurodehydrocholate
      (TDHC); group 4, sham laparotomy; and group 5, nonoperated controls where Fe
      absorption was measured from three doses of 59Fe-FeSO4 at the same time intervals
      as group 1. Absorption was measured, using whole body counting, after achievement
      of steady-state counts after each Fe dose. Mean percentage absorption from dose 1
      (baseline) was 35.33 +/- 4.6% (SE). No significant differences between any groups
      were noted. In nonoperated controls (group 4), Fe absorption was virtually
      identical after all three doses. Also, hematocrit did not change in any of the 30
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141306
TI  - Endothelin-1 stimulates bile acid secretion and vesicular transport in the
      isolated perfused rat liver.
AB  - The effects of endothelin (ET) on portal pressure and bile secretion were
      examined using isolated perfused rat liver and rat hepatocyte preparations. ET-1
      raised portal pressure dose dependently; administration at a high dose (10(-9)
      mol) induced a > 200% increase along with reduced bile flow and decreased
      secretion of bile acid and phospholipids. However, a low dose (10(-10) mol) of ET
      1 brought about a < 100% portal pressure rise, enhanced both bile flow and
      excretion of bile acid and phospholipids, and significantly increased transfer of
      preadministered horseradish peroxidase (HRP) into bile. In addition, values for
      Ca2+ concentrations, examined by indo 1 fluorescence, were elevated in isolated
      hepatocytes after administration of ET-1. Papaverine suppressed the low-dose ET-1
      stimulation effects on both portal pressure and bile secretion. Moreover, it also
      reduced the HRP excretion and suppressed intracellular Ca2+ release. This study
      demonstrated that ET-1 stimulates vesicular transport, probably via promotion of
      intracellular Ca2+ release, and, as a result, increases bile acid-dependent bile
      flow.

PMID- 8141307
TI  - Calcium requirements for acetylcholine-induced contraction of cat esophageal
      circular muscle cells.
AB  - Esophageal circular muscle cells isolated by enzymatic digestion contracted in
      response to acetylcholine (ACh) and in response to the protein kinase C (PKC)
      agonist 1,2-dioctanoylglycerol (1,2 DAG). Both responses were blocked by PKC
      antagonists but not by calmodulin antagonists. Furthermore, specific PKC
      activity, measured in the particulate fraction of the muscle, increased in
      response to cholinergic stimulation, suggesting that ACh-induced contraction is
      mediated by a PKC-dependent pathway. ACh-induced contraction decreased with
      decreasing extracellular Ca2+ and was blocked in Ca(2+)-free physiological salt
      solution (PSS). Similarly, contraction by the nonhydrolyzable GTP analogue
      guanosine 5'-O-(3-thiotriphosphate) was blocked by removal of Ca2+ from the PSS.
      Diacylglycerol production in response to ACh was reduced when extracellular Ca2+
      was reduced from 2 to 0.5 mM and was abolished in Ca(2+)-free PSS. The response
      to 1,2-DAG, however, did not significantly change as extracellular Ca2+ or
      cytosolic Ca2+ was reduced to zero. Heparin (10 micrograms/ml), thapsigargin (3
      microM), or the Ca2+ ionophore A-23187 (3 microM) had no effect on 1,2-DAG or ACh
      induced contraction in permeable cells. The data suggest that contraction in
      response to ACh is mediated by influx of extracellular Ca2+ and a PKC-dependent
      pathway. Ca2+ may be required mainly to activate the phospholipases responsible
      for production of diacylglycerol, since contraction of esophageal muscle cells in
      response to 1,2-DAG is Ca2+ independent.

PMID- 8141308
TI  - ETA and ETB receptors on single smooth muscle cells cooperate in mediating guinea
      pig tracheal contraction.
AB  - We investigated the distribution of endothelin A (ETA) and ETB receptors in
      single smooth muscle cells and their contribution to ET-induced contractions of
      guinea pig trachea. ETA and ETB receptors were detected in smooth muscle
      membranes (maximum binding capacities of 810 and 360 fmol/mg protein and
      dissociation constants of 38 and 5.1 pM for 125I-labeled ET-1 and 125I-ET-3,
      respectively) and visualized autoradiographically in primary cultured cells. ET-1
      and ET-3 evoked concentration-dependent increases in intracellular Ca2+
      concentration and smooth muscle tension. The half-maximally effective
      concentrations of ET-1 and ET-3 at inducing contractions were 1.9 and 2.7 nM,
      respectively. The Ca2+ responses showed tachyphylaxis to both ETs after
      stimulation with ET-1, but only to ET-3 after stimulation with ET-3. Consecutive
      applications of ET-3 and ET-1 (10 nM each) classified the cells into ETA dominant
      (approximately 30%) responding to only ET-1, ETB dominant (approximately 20%)
      responding to only ET-3, and ETA- and ETB-possessing (approximately 50%) cells
      responding to both. The ETA antagonist, 10 microM BQ-123, attenuated ET-1-induced
      contractions but did not affect the ET-3-induced contractions. The results
      indicate that both receptors coexist in a major population of smooth muscle cells
      and cooperate in mediating ET-1-induced contractions.

PMID- 8141309
TI  - Polarized distribution of Na(+)-H+ antiport activity in rat alveolar epithelial
      cells.
AB  - In this study, we investigated the polarized distribution of Na(+)-H+ antiport
      activity in alveolar epithelial cell monolayers. Rat alveolar type II pneumocytes
      were grown on detachable tissue culture-treated Nuclepore filters. The membrane
      filters, with their adherent intact alveolar epithelial cell monolayers, were
      mounted in a cuvette designed to contain two fluid compartments separated by the
      monolayer. Cells were loaded with the pH-sensitive dye 2',7'-biscarboxyethyl-5,6
      carboxylfluorescein and intracellular pH (pHi) measured spectrofluorometrically.
      Monolayers were studied at ambient temperature on days 3-4 in culture, coincident
      with the development of high tissue resistance (RT > or = 2000 omega.cm2). Cells
      were incubated in HCO(3-)-free Na+ buffer [(in mM) 140 NaCl, 6 HEPES, pH 7.4] and
      acidified by NH3 prepulse. Rates of realkalinization (JH+) were calculated as the
      product of the initial rate of recovery (dpHi/dt) and the intracellular buffer
      capacity (beta i). Under control conditions, recovery occurred with an initial
      JH+ of 28.4 mM/min. When 100 microM dimethylamiloride (DMA), an amiloride
      analogue with enhanced specificity for inhibiting the Na(+)-H+ antiporter, was
      present in the basolateral fluid, recovery was inhibited by > 90%. Conversely,
      when the monolayers were acidified in Na+ buffer containing DMA (100 microM) in
      the apical fluid, acidification and recovery were identical to control. Recovery
      from acidification was inhibited by basolateral DMA with a one-half maximal
      inhibitory concentration (IC50) of 100 nm and by basolateral amiloride with an
      IC50 of 10 microns. Recovery was completely inhibited by omission of Na+ from the
      basolateral fluid, but omission of Na+ from apical fluid had no effect. We
      conclude that Na(+)-H+ antiport activity is located exclusively on the
      basolateral surface of these alveolar epithelial cell monolayers, where it most
      likely represents the high-amiloride affinity isoform of the Na(+)-H+ antiporter,
      NHE-1. The Na(+)-H+ antiporter, asymmetrically distributed to the basolateral
      surface of the polarized alveolar epithelium, contributes to intracellular
      homeostasis in alveolar pneumocytes and may also play a role in signal
      transduction in these cells.

PMID- 8141310
TI  - Secretion of cytokines by rat alveolar epithelial cells: possible regulatory role
      for SP-A.
AB  - Cultured alveolar type II cells and pulmonary epithelial (PE) cells in long-term
      culture were found to secrete colony-stimulating factors (CSF) into the medium in
      similar fashion to alveolar macrophages. CSF activity was determined by using the
      in vitro assay for myeloid progenitor cells [colony-forming units in culture (CFU
      C)]. Both lipopolisaccharide (LPS) and interleukin-1 alpha (IL-1 alpha) were
      found to upregulate the secretion 6.5- to 8-fold from alveolar type II cells and
      macrophages. However, no stimulatory effect of these factors was observed in PE
      cells that release CSF into the medium constitutively, possibly due to the
      conditions of long-term culture. The CSF activity was partially neutralized (70%
      inhibition) by antibodies against murine granulocyte/macrophage (GM)-CSF and IL
      3, thus indicating the presence of both GM-CSF and IL-3-like factors in the CSF.
      However, the presence of other cytokines in the CSF is highly probable.
      Surfactant-associated protein A (SP-A), which is known to play a central role in
      surfactant homeostasis and function, was also found to upregulate secretion of
      CSF (at concentrations of 0.1-5 micrograms/ml) from alveolar type II cells and
      macrophages. Control cells such as rat peritoneal macrophages, alveolar
      fibroblasts, and 3T3/NIH cell line could not be elicited by SP-A to release CSF.
      The results are discussed in relation to the possible participation of the
      alveolar epithelial cells in various intercellular signaling networks. Our
      studies suggest that alveolar type II cells and SP-A may play an important
      regulatory role in the modulation of immune and inflammatory effector cells
      within the alveolar space.

PMID- 8141311
TI  - Airway vasodilation by bradykinin is mediated via B2 receptors and modulated by
      peptidase inhibitors.
AB  - We studied the effect of exogenous bradykinin on blood flow in the airway
      microcirculation of anesthetized F344 rats in vivo. We made three successive
      determinations of airway blood flow and cardiac output using a modification of
      the reference sample microsphere technique. Injection of bradykinin into the left
      ventricle increased airway blood flow in a dose-related manner. Pretreatment with
      the bradykinin B2 receptor antagonist, Hoe 140, completely abolished bradykinin-,
      but not histamine-induced vasodilation. A bradykinin B1 receptor agonist, [des
      Arg9]bradykinin, did not affect airway blood flow. We also studied the effect of
      inhibitors of angiotensin-converting enzyme (captopril) and neutral endopeptidase
      (phosphoramidon) on bradykinin-induced vasodilation. Pretreatment with captopril,
      but not phosphoramidon, potentiated the bradykinin-induced vasodilation. However,
      the addition of phosphoramidon further potentiated the effect of captopril. We
      conclude that injection of bradykinin into the left ventricle produces a dose
      related vasodilation in the airway microcirculation mediated via B2 receptors, an
      effect that is modulated primarily by angiotensin-converting enzyme and, to a
      lesser extent, by neutral endopeptidase.

PMID- 8141312
TI  - Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene
      expression by oxygen tension.
AB  - Recent studies have demonstrated that xanthine dehydrogenase/xanthine oxidase
      (XD/XO) activities of bovine endothelial cells (EC) are inversely regulated by O2
      tensions to which the cells are exposed. We have confirmed these reports and
      extended the observation to a variety of cells from other sources. All EC that
      had detectable XD/XO activity demonstrated the greatest activity at the lowest O2
      level. Bovine pulmonary artery smooth muscle cells showed XD/XO activity only
      under hypoxic conditions. The ratio of XO to XO+XD did not change significantly
      under various O2 concentrations for all cell types tested. Treatment of bovine
      pulmonary artery and rat epididymal fat pad EC with actinomycin D (1
      microgram/ml), an inhibitor of transcription, suppressed XO and XO+XD activities
      in cells exposed both to 20 and 3% O2. High-dose cycloheximide (5 micrograms/ml),
      an inhibitor of translation, also reduced XO and XO+XD activities in these cells,
      whereas low-dose cycloheximide (0.5 microgram/ml) enhanced the stimulatory effect
      of hypoxia on XO+XD activity. We developed a digoxigenin-labeled probe that
      recognizes and hybridizes to rat XD cDNA and used it to examine the effect of O2
      concentration on XD/XO mRNA expression of rat epididymal fat pad EC. XD/XO mRNA
      concentration was increased in cells exposed to hypoxia and decreased in cells
      exposed to hyperoxia compared with normoxic cells. The increase in mRNA
      concentration resulting from exposure to hypoxia was enhanced by cycloheximide.
      There was no change in XD/XO mRNA stability in cells exposed to hypoxia compared
      with normoxia. We conclude that the regulation of XD/XO by oxygen tension most
      likely occurs at the transcriptional level.

PMID- 8141313
TI  - Serotonin increases DNA synthesis in rat proximal and distal pulmonary vascular
      smooth muscle cells in culture.
AB  - Cultured smooth muscle cells obtained from rat lung periphery (RPC) and proximal
      pulmonary artery (RSMC) expressed mRNA for serotonin (5-HT) type 2 receptor (5
      HT2) and 5-HT transporter (by Northern blot analysis). Functional expression of
      these genes was evident since both cell types 1) bound 125I-labeled lysergic acid
      diethylamide (LSD; 5-HT2 receptor antagonist) that was equally effectively
      displaced by either ketanserin or mianserin; and 2) transported 5-[3H]HT in an
      imipramine-sensitive manner. Serotonin (10(-9)-10(-5) M) stimulated DNA synthesis
      (as measured by [3H]thymidine uptake) in RPC and RSMC. The 5-HT-induced increase
      in DNA synthesis was significantly inhibited in both cell types by the 5-HT2
      receptor antagonist, ketanserin (10(-7)-10(-6) M), and by fluoxetine (10(-6) M),
      a putative 5-HT transport inhibitor. Acute exposure to 5-HT (1-100 microM) caused
      an abrupt rise in intracellular calcium ([Ca2+]i) in single pulmonary vascular
      smooth muscle cells as microspectrofluorometrically determined using the calcium
      sensitive dye, fura 2. The 5-HT-induced change in [Ca2+]i was completely
      abolished in the presence of 10(-6) M ketanserin as well as imipramine or
      fluoxetine (10(-6) M). The calcium transients due to 5-HT persisted in a Na(+)
      free condition (in which the transporter activity was completely abolished) and
      imipramine and fluoxetine (and ketanserin) were effective inhibitors of 5-HT
      under these conditions. Therefore, the 5-HT2 receptor, but not the transporter,
      is responsible for initiating the acute effects (e.g., calcium transients) of 5
      HT in cultured rat pulmonary vascular smooth muscle cells and fluoxetine (1
      microM) may have 5-HT2-receptor antagonist properties.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8141314
TI  - TGF-beta 1 modulates beta-adrenergic receptor number and function in cultured
      human tracheal smooth muscle cells.
AB  - Pretreatment of cultured human tracheal smooth muscle cells with transforming
      growth factor-beta 1 (TGF-beta 1) decreased adenosine 3',5'-cyclic monophosphate
      (cAMP) accumulation by intact cells stimulated with the beta-adrenergic agonist
      isoproterenol. The maximal inhibition of isoproterenol-stimulated cAMP
      accumulation by TGF-beta 1 was 31 +/- 3%, and the mean effective concentration
      (EC50) of TGF-beta 1 was approximately 1.5 pM. TGF-beta 1 decreased the maximal
      response to isoproterenol but did not change the EC50 value of isoproterenol. TGF
      beta 1 did not change cAMP accumulation stimulated by forskolin. TGF-beta 1
      pretreatment decreased isoproterenol-stimulated adenylyl cyclase activity
      measured in broken cell preparations, but did not change the fluoride-stimulated
      adenylyl cyclase activity. Together these results suggest that the TGF-beta 1
      effect is not by direct inhibition of adenylyl cyclase or by decreased activity
      of the stimulatory GTP-binding protein. Saturation binding experiments with the
      beta-adrenergic receptor radioligand [125I]iodopindolol showed that TGF-beta 1
      pretreatment decreased the beta-adrenergic receptor number. The protein synthesis
      inhibitor cycloheximide abolished the effect of TGF-beta 1 on both cAMP
      accumulation and on beta-adrenergic receptor number, indicating that protein
      synthesis is involved. These results suggest that TGF-beta 1 in the lung could
      play a role in changing the responsiveness of airway smooth muscle cells to
      endogenous catecholamines and to beta-adrenergic agonists used in therapy.

PMID- 8141315
TI  - Pseudomonas siderophore pyochelin enhances neutrophil-mediated endothelial cell
      injury.
AB  - Pyochelin, a siderophore secreted by Pseudomonas aeruginosa, binds iron in a form
      which can catalyze the formation of hydroxyl radical (.OH) from neutrophil
      derived superoxide (O2-.) and hydrogen peroxide (H2O2). Ferripyochelin induced a
      concentration-dependent increase in endothelial cell injury (51Cr release)
      resulting from exposure to H2O2, a xanthine/xanthine oxidase O2-./H2O2 generating
      system, or stimulated neutrophils. This process was dependent on the presence of
      iron. Formation of .OH was confirmed using spin trapping. Although a slight (13%)
      increase in neutrophil O2-. production in the presence of ferripyochelin was
      observed, this did not appear to account for the extent of endothelial cell
      injury observed. The antioxidants dimethylthiourea and catalase decreased
      endothelial cell injury, whereas dimethyl sulfoxide and superoxide dismutase were
      without effect. Fe-nitrilotriacetic acid and Fe-EDTA, which are also .OH
      catalysts, did not augment endothelial cell injury resulting from exposure to the
      above oxidant systems. In contrast to results with the endothelial cells, killing
      of P. aeruginosa by O2-./H2O2 derived from the reaction of xanthine and xanthine
      oxidase was not increased by ferripyochelin. These data are consistent with the
      possibility that the interaction of Pseudomonas- and phagocyte-derived secretory
      products could contribute to local tissue injury at sites of P. aeruginosa
      infection by causing the generation of .OH.

PMID- 8141316
TI  - Effects of halothane on the relationship between cytosolic calcium and force in
      airway smooth muscle.
AB  - The mechanism of the direct relaxing effect of halothane on airway smooth muscle
      may involve a decrease in 1) cytosolic calcium concentration ([Ca2+]i) and/or 2)
      the force produced for a given [Ca2+]i (i.e., the "sensitivity" of the
      myofibrillar contractile system to Ca2+). This study was conducted to test the
      hypothesis that halothane reduces the sensitivity of the myofibrillar contractile
      system to Ca2+ during muscarinic receptor stimulation of canine tracheal smooth
      muscle. Isolated smooth muscle strips were mounted in a photometric superfusion
      system, stretched to their optimal length for force development, and loaded with
      the fluorescent Ca2+ indicator, fura 2, for simultaneous recording of fura 2
      fluorescence and isometric force. Emission fluorescence intensities due to
      excitation at 340 (F340)- and 380 (F380)-nm wavelengths were measured and
      F340/F380 was used as an index of [Ca2+]i. After superfusion with Ca(2+)-free
      physiological salt solution (PSS) containing 1 or 100 microM acetylcholine (ACh),
      two consecutive cumulative concentration-response curves to CaCl2 (0.01-2.4 mM)
      were generated for each strip; one curve was generated in the presence of
      halothane. In strips stimulated with 1 (n = 6) or 100 (n = 6) microM ACh, the
      cumulative addition of CaCl2 to the Ca(2+)-free PSS caused concentration
      dependent increases in both F340/F380 and force. In strips stimulated with 1
      microM ACh, 2.4 +/- 0.3% halothane proportionally attenuated increases in both
      F340/F380 and force.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141317
TI  - Hereditary and acquired defects in signaling through the hormone-receptor-G
      protein complex.
AB  - Extracellular signals reach the interior of cells as second messengers through
      intermediary transducers located within or closely associated with the plasma
      membrane. One of the most common pathways involves the interaction of the
      extracellular signaling element with a membrane-bound receptor and guanine
      nucleotide-binding regulatory protein (G protein). Inherited and acquired defects
      that alter the function of the first messenger (hormone, neurotransmitter,
      autacoid, or paracrine substance) or either of the transducing components (G
      protein-coupled receptor or G protein) can lead to defective signaling and,
      ultimately, disease. Clinically relevant examples of defects of all three of
      those signaling components have recently been described. These can take the form
      of inherited or sporadic mutations of the genes encoding the various signaling
      components, or of neutralizing antibodies against those components. The purpose
      of this review is to summarize how acquired or inherited defects in each of those
      pathways might lead to diseases.

PMID- 8141318
TI  - Renal cortical interstitium and fluid absorption by peritubular capillaries.
AB  - Every minute, the cortical peritubular capillaries in a 1-g rat kidney take up
      more than 0.5 ml tubular reabsorbate. Studies of renal lymph and measurements of
      pressure in capillaries (Pc) and interstitium (Pi) indicate that normally the
      protein colloid osmotic pressure of peritubular capillary plasma (COPp) provides
      the necessary absorptive force, keeping Pi at 2-4 mmHg, i.e., 8-10 mmHg lower
      than Pc. At reduced COPp, continued delivery of fluid from the tubules
      automatically raises Pi to maintain capillary fluid uptake. The transient Pi
      response to sudden exposure of the kidney to subatmospheric pressure shows that
      such adjustment of forces may take place in only 5 s. Most remarkable, adjustment
      of forces may take place in only 5 s. Most remarkable, reabsorption continues
      during protein-free perfusion of the isolated rat kidney, apparently effected by
      a Pi exceeding Pc. A relative retardation of interstitial uptake of ferritin from
      plasma in this case suggests fluid reabsorption through both small and large
      pores in the capillary wall. Collapse of the capillaries is presumably prevented
      by tight tethering to the capillary wall, giving the narrow interstitium a very
      low compliance.

PMID- 8141319
TI  - Metabolic acidosis stimulates carbonic anhydrase activity in rabbit proximal
      tubule and medullary collecting duct.
AB  - Both membrane-bound carbonic anhydrase (CA) (isozyme type IV) and cytosolic CA
      (type II) activities enhance urinary acidification. We have previously shown that
      chronic metabolic acidosis (CMA) accomplished by NH4Cl loading with food
      restriction induces soluble CA activity in rabbit renal cortical homogenates. The
      present study was designed to assess the effect of CMA on the activity of CA
      isozymes in cortical and outer medullary homogenates, as well as in major proton
      secreting segments of the kidney. Segments were microdissected from proximal
      convoluted tubules (PCT) proximal straight tubules, cortical collecting ducts,
      and outer medullary collecting ducts (OMCD). Total CA activity was measured by a
      colorimetric endpoint method, and CA IV activity was assessed from the sodium
      dodecyl sulfate-resistant hydratase activity. In controls, CA IV activity
      accounted for 3% of total CA activity in tissue homogenates. CMA induced a
      threefold increase in CA IV activity in cortical homogenates, in the absence of
      renal or tubular hypertrophy. In the PCT, CMA induced a 78% increase in total CA
      activity, which comprised a 178% increase in CA IV activity, and a 58% increase
      in CA II activity. In the OMCD, CMA induced a 53% increase in total CA (probably
      CA II) activity. We conclude that CMA induces CA activity in the PCT (CA II and
      CA IV) and the OMCD (most likely CA II) of adult rabbit kidneys. The induction of
      CA activity accompanies the increase in urinary acidification observed in CMA.

PMID- 8141320
TI  - Ca2+ uptake, fatty acid, and LDH release during proximal tubule hypoxia: effects
      of mepacrine and dibucaine.
AB  - In freshly isolated hypoxic rat proximal tubules, Ca2+ uptake rate increases
      promptly, within 1 min, and remains significantly elevated throughout a 20-min
      period of hypoxia. Lactate dehydrogenase (LDH) release, a sign of membrane
      injury, increases only after 5 min of hypoxia and thereafter rises progressively.
      The potential effect of increased Ca2+ uptake rate to activate phospholipases,
      which would then initiate membrane injury, was evaluated by treating hypoxic
      tubules with three dissimilar phospholipase inhibitors, i.e., mepacrine,
      dibucaine, or p-bromophenacyl bromide (PBPB). LDH release averaged 11.9 and 13.8%
      after 10 and 20 min of normoxia, respectively. With 10 or 20 min of hypoxia LDH
      release increased to 46.0 and 65.2%, respectively (P < 0.01), and Ca2+ uptake
      rate increased from 2.56 in normoxia to 4.71 nmol.mg-1 x min-1 at 10 min of
      hypoxia (P < 0.01) and from 2.82 in normoxia to 3.76 nmol/mg at 20 min of hypoxia
      (P < 0.05). In a separate series of tubules, after 10 min of hypoxia LDH release
      was reduced by pretreatment with 50 microM mepacrine (66.1 to 47.3%, P < 0.01) or
      50 microM dibucaine (53.1 to 38.5%, P < 0.02). The increase in Ca2+ uptake rate
      also was significantly reduced. After 20 min of hypoxia neither mepacrine nor
      dibucaine reduced Ca2+ uptake rate; LDH release was modestly reduced by dibucaine
      but not mepacrine. Higher doses of mepacrine (500 microM) and dibucaine (250
      microM) also reduced cell injury at 10 min of hypoxia as assessed by LDH
      release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141321
TI  - Effect of luminal angiotensin II on proximal tubule fluid transport: role of
      apical phospholipase A2.
AB  - Recent micropuncture studies showed the existence of high concentrations of
      angiotensin II (ANG II) in proximal tubular fluid. In the present study, we have
      examined the effect of luminal ANG II, alone and in combination with peritubular
      ANG II, on fluid transport (JV) in the isolated perfused rabbit proximal
      convoluted tubule. In comparison with peritubular ANG II, luminal ANG II caused a
      similar but more potent biphasic effect on JV. At 10(-11) M, luminal ANG II
      maximally increased JV to 204 +/- 22% of the baseline compared with 142 +/- 10%
      by peritubular ANG II at 10(-10) M. At 10(-8) M, luminal ANG II suppressed JV to
      9.7 +/- 16% of the baseline compared with 64 +/- 14% by peritubular ANG II. When
      luminal and peritubular ANG II were combined at concentrations that impose
      similar effect on JV, the effects of luminal and peritubular ANG II were not
      additive. However, when combined at concentrations that would otherwise impose
      opposing effects on JV, the stimulatory effect predominated. In support of the
      role of apical phospholipase A2 (PLA2) on the effect of luminal ANG II, ANG II
      stimulated PLA2 activity in isolated brush-border membrane vesicles, and addition
      of PLA2 inhibitor, mepacrine or dibucaine, to the luminal perfusate attenuated
      the effect of luminal ANG II on JV. In summary, these studies show a potent
      effect of luminal ANG II on proximal tubule JV involving activation of brush
      border membrane PLA2. When combined, luminal and peritubular ANG II exert their
      effects in concert on proximal tubule JV.

PMID- 8141322
TI  - ATP stimulates Ca2+ mobilization by a nucleotide receptor in glomerular
      endothelial cells.
AB  - The present study investigates ATP effects on Ca2+ mobilization in bovine
      glomerular endothelial cells (GEC) and the receptors mediating ATP response.
      Extracellular ATP stimulated a rise in inositol 1,4,5-trisphosphate and cytosolic
      free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. Extracellular Ca2+
      depletion did not prevent [Ca2+]i rise. ATP effects were not mediated by P1, P2x,
      and P2t purinoceptors, since the P1 receptor agonist adenosine and the P2x
      receptor agonist [alpha,beta-CH2]ATP had no effect on inositol 1-monophosphate
      (IP) formation and Ca2+ mobilization and ATP does not activate P2t receptors. The
      P2y receptor antagonist reactive blue (10(-3) M) had little inhibitory effect on
      ATP (10(-5) M)-stimulated IP formation (15.6 +/- 4.2%) and Ca2+ rise (7.0 +/-
      3.0%). According to the classification of purinoceptors, ATP is less potent than
      2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) in stimulating P2y receptors.
      In GEC, however, the rank order of potency in stimulating IP and [Ca2+]i rise was
      ATP > 2-MeS-ATP > ADP. The pyrimidine nucleotide UTP (10(-3) M) induced maximal
      IP formation (653 +/- 37%) and Ca2+ mobilization (591 +/- 22 nM) similar to ATP
      (IP 647 +/- 27%; [Ca2+]i 583 +/- 15 nM). At submaximal (10(-5) M) but not at
      maximal (10(-3) M) doses ATP and UTP effects were additive. ATP and UTP induced
      specific cross-desensitization. It is concluded that the purinergic nucleotide
      ATP and pyrimidine nucleotide UTP mediate their effects by a common nucleotide
      receptor. This receptor differs from P2z and P2y1 receptors, since by definition
      UTP does not activate these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141323
TI  - Mechanism of acidification along cortical distal tubule of the rat.
AB  - The cellular mechanism of luminal acidification (bicarbonate reabsorption) was
      studied in cortical distal tubules of rat kidney. The stopped-flow microperfusion
      technique was applied to early distal (ED) and late distal (LD) segments,
      perfused with bicarbonate Ringer solution to which specific inhibitors were
      added, to measure bicarbonate reabsorption [HCO3 flux (JHCO3)]. pH and
      transepithelial potential difference (Vt) were recorded by double-barreled H+
      exchange resin/reference (1 M KCl) electrodes. Amiloride increased stationary pH
      and reduced Vt in both early and late segments. Hexamethylene-amiloride (HMA), a
      specific Na(+)-H+ exchange blocker, reduced JHCO3 in both segments (ED by 43.6
      and LD by 40.3%) without affecting Vt. Benzamil, an Na(+)-channel blocker,
      reduced Vt by 75.9 in ED and 74.9% in LD but had no significant effect on
      acidification in both segments. The specific inhibitor of H(+)-ATPase,
      bafilomycin A1, inhibited LD JHCO3 at a concentration of 2 x 10(-7) M by 49%, but
      ED was inhibited by 24% only at 2 x 10(-6) M. Sch-28080, an inhibitor of gastric
      H(+)-K(+)-ATPase, reduced JHCO3 by 35% in LD of K(+)-depleted rats but not in
      control rats and had no effect on ED. These data indicate that, in ED,
      bicarbonate reabsorption is mediated mostly by Na(+)-H+ exchange. In LD, there is
      evidence for contribution of Na(+)-H+ exchange, vacuolar H(+)-ATPase, and H(+)
      K(+)-ATPase (in K(+)-depleted rats) to bicarbonate reabsorption.

PMID- 8141324
TI  - Synergistic effects of angiotensin and adenosine in the renal microvasculature.
AB  - Experiments were performed in the in situ kidney of rats and in isolated afferent
      arterioles of the rabbit to study the interaction between angiotensin II and
      adenosine in producing afferent arteriolar vasoconstriction. In the intact rat
      kidney, we observed that 1) peritubular infusion of the adenosine1-receptor
      blocker 8-cyclopentyl-1,3-dipropylxanthine (CPX, 10(-4) M) blocked the fall in
      stop-flow pressure (PSF) induced by angiotensin II (5 x 10(-7) M) but not that
      caused by vasopressin (10(-5) M) or norepinephrine (10(-5) M), 2) peritubular
      infusion of saralasin (5 x 10(-5) M) attenuated the fall in PSF caused by N6
      cyclohexyladenosine (CHA, 10(-5) M) 3) the fall in PSF following luminal
      application of CHA (10(-5) M) was reduced in angiotensin II-depleted states
      (volume expansion and converting enzyme inhibition) and this could be reversed by
      infusion of low doses of angiotensin II, and 4) the reduction in PSF in response
      to luminal infusion of CHA was augmented in a greater-than-additive fashion when
      angiotensin was simultaneously administered at low intravenous infusion rates. In
      isolated afferent arterioles of the rabbit, we noted that 1) addition of 10(-5) M
      CPX to the bath significantly blunted the constrictor effect of angiotensin II
      (10(-8) M), 2) presence of the converting enzyme inhibitor quinaprilate (10(-7)
      M) caused a right shift in the constrictor-response curve to increasing
      concentrations of CHA (10(-9)-10(-5) M) but 10(-5) M saralasin did not affect
      vasoconstriction caused by 10(-6) M adenosine, 3) simultaneous administration of
      submaximal constrictor doses of angiotensin II (10(-10) M) and adenosine (10(-6)
      M) produced vasoconstriction that was greater than additive, and 4) 10(-5) M CHA
      and angiotensin II (10(-7) M) constricted afferent arterioles after removal of
      the glomerulus, whereas either agent alone had no constrictor effect in this
      preparation. Our results suggest that adenosine and angiotensin cooperate in a
      mutually dependent and synergistic fashion in producing afferent arteriolar
      vasoconstriction.

PMID- 8141326
TI  - Conductive properties of papillary surface epithelium.
AB  - The surface epithelium of rabbit renal papilla was dissected free from its
      supporting tissue and mounted in an Ussing chamber. The conductive properties of
      the epithelium and of the apical and basolateral cell membranes were examined
      with KCl-filled microelectrodes. The transepithelial voltage was 0.07 +/- 0.15
      mV, and the transepithelial resistance was 107 +/- 15 omega.cm2 (n = 29). The
      fractional resistance of the apical membrane (fRa) was 0.93 +/- 0.01 (n = 103
      cells, 29 tissues). The apical membrane was not conductive to Na+, K+, or Cl-. An
      increase in the K+ concentration of the basolateral solution from 5 to 50 mM
      depolarized the basolateral membrane voltage (Vb) from -59 +/- 1.6 to -31.2 +/-
      2.2 mV (n = 28 cells) and increased fRa from 0.935 +/- 0.01 to 0.962 +/- 0.01 (P
      < 0.001, n = 21 cells). Likewise, 5 mM barium in the basolateral solution
      depolarized Vb from -57.7 +/- 2.0 to -29.8 +/- 2.2 mV (n = 21 cells). A tenfold
      decrease in the Cl- concentration of the basolateral solution caused an 8.3 +/-
      1.9 mV depolarization in Vb. Thus the basolateral cell membrane is conductive to
      K+ and Cl-. Exposure of the apical membrane to amphotericin B demonstrated that
      the transepithelial resistance is determined primarily by the paracellular
      pathway.

PMID- 8141325
TI  - Expression of Na-K-ATPase alpha- and beta-subunit mRNA and protein isoforms in
      the rat nephron.
AB  - Na-K-ATPase is a heterodimeric complex composed of an alpha-catalytic and a
      glycosylated beta-subunit. Previous studies using in situ hybridization and
      Northern blot analysis to determine alpha- and beta-subunit mRNA isoform
      expression in the rat kidney have given conflicting results. This heterogeneity
      may be due to detection of alpha 2- or alpha 3-isoforms arising from nonrenal
      epithelial sources such as peripheral nerves or vascular smooth muscle. To
      address this possibility, we investigated alpha-subunit mRNA isoform expression
      in different nephron segments using tubule microdissection and reverse
      transcription-polymerase chain reaction amplification. Southern blot analysis of
      polymerase chain reaction products using isoform-specific primers and probes
      detected the expression of alpha 1- and alpha 3-mRNA isoforms in whole kidney,
      cortical collecting ducts (CCD), and proximal tubule S2 subsegments (S2). No
      evidence for alpha 2 was found in kidney or microdissected CCD or S2. To
      determine whether alpha 1- or alpha 3-mRNA in the CCD or S2 is translated into
      protein, Western blot analysis of total protein from microdissected S2, CCD,
      medullary thick ascending limb (MTAL), or outer medullary collecting duct outer
      stripe (OMCDos) was performed. Total protein was separated according to size by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, then probed using
      polyclonal antibodies specific for the alpha 1-, alpha 2-, alpha 3-, beta 1-, and
      beta 2-protein isoforms. Rat brain was used as a positive control and
      demonstrated that the antibodies could detect a single 97- and 35-kDa band for
      the alpha- and beta-isoforms, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141327
TI  - Polarized distribution of oxalate transport systems in LLC-PK1 cells, a line of
      renal epithelial cells.
AB  - Although oxalate is a major component of kidney stones, the factors affecting
      renal oxalate handling are poorly understood. This uncertainty stems in part from
      complexities inherent to available preparations; thus the present studies
      examined oxalate handling in a simpler model system, LLC-PK1 cells, an epithelial
      cell line of porcine origin. Initial studies on monolayers in dishes demonstrated
      that these cells accumulate oxalate via a process or processes sensitive to the
      anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
      (DIDS). Subsequent studies using LLC-PK1 monolayers on membrane filters examined
      the characteristics and distribution of these transporter(s). At the apical
      surface, DIDS-sensitive uptake was sensitive to [Cl-] but not [SO4(2-)] or [HCO3
      ] and was unaffected by alterations in pH or membrane potential. At the
      basolateral surface, oxalate uptake was [Cl-] insensitive but markedly affected
      by variation in pH, [SO4(2-)], or [HCO3-]. Uptake at the two membrane surfaces
      was also differentially affected by transport inhibitors and organic acids. Thus
      LLC-PK1 cells appear to express unique transporters at each membrane surface:
      oxalate/Cl- exchange at the apical surface and oxalate/SO4(2-) (or HCO3-)
      exchange at the basolateral surface.

PMID- 8141328
TI  - Inhibition of renal vascular 20-HETE production impairs autoregulation of renal
      blood flow.
AB  - The present study evaluated the role of endogenous P-450 metabolites of
      arachidonic acid (AA) on autoregulation of renal blood flow in rats. Whole kidney
      and cortical blood flows were well autoregulated when renal perfusion pressure
      was varied from 150 to 100 mmHg. Infusion of 17-octadecynoic acid (17-ODYA) into
      the renal artery (33 nmol/min) increased cortical and papillary blood flows by
      12.6 +/- 2.5 and 26.5 +/- 4.6%, respectively. After 17-ODYA, autoregulation of
      whole kidney and cortical blood flows was impaired. Intrarenal infusion of
      miconazole (8 nmol/min) had no effect on autoregulation of whole kidney,
      cortical, or papillary blood flows. 17-ODYA (1 microM) inhibited the formation of
      20-hydroxyeicosatetraenoic acid (20-HETE) and 11,12- and 14,15
      epoxyeicosatrienoic acids (EETs) by renal preglomerular microvessels in vitro by
      83.7 +/- 7.4% and 89.0 +/- 4.9%, respectively. Miconazole (1 microM) reduced the
      formation of EETs by 86.4 +/- 5.7%, but it had no effect on the production of 20
      HETE. These results suggest that endogenous P-450 metabolites of AA, particularly
      20-HETE, may participate in the autoregulation of renal blood flow.

PMID- 8141329
TI  - Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic
      rats.
AB  - The renal reabsorption of glucose is mediated by two major classes of
      transporters. Initially, luminal glucose is concentrated in tubules by Na(+)
      glucose cotransporters (Na(+)-GLUT). Afterwards, glucose reaches the blood space
      through facilitative glucose transporters, low-Michaelis constant (Km) GLUT1 and
      high-Km GLUT2. Hence, the transtubular flux of glucose could be impaired in
      hyperglycemia because the outwardly directed glucose gradient, from tubule to
      blood, is potentially lowered. However, in diabetic rats, transtubular glucose
      flux is not reduced but increased. In this work the molecular mechanism
      underlying this adaptation was examined. We tested the hypothesis that
      upregulation of renal tubular high-Km GLUT2 gene may compensate for the decrease
      in the tubule to blood glucose gradient. In rat tubules, GLUT1 protein and mRNA
      steady-state levels were reduced, and GLUT2 protein and mRNA levels were
      increased in rats after 2, 3, and 4 wk of uncontrolled streptozotocin-induced
      diabetes. These molecular adaptations were associated with augmented facilitative
      glucose flux. In summary, changes in GLUT1 and GLUT2 gene expression are
      important to the preservation of renal glucose reabsorption in hyperglycemia.

PMID- 8141331
TI  - Growth and characterization of porcine urinary bladder epithelial cells in vitro.
AB  - Dividing long-term monolayer cultures of porcine urinary bladder epithelial cells
      were obtained by a combined mechanical and enzymatic isolation method. The serum
      free cultured cells were investigated morphologically and characterized according
      to their growth characteristics and enzymatic functions. Investigations over a
      period up to 12 wk demonstrated that the cells regain their in vivo polarization
      with apically situated membrane vesicles and tight junctions between neighboring
      cells when they have built up a confluent monolayer. Activities of most marker
      enzymes for cell-differentiated status and function of such cells observed over a
      period of 4 wk in culture were conserved compared with the original tissue.
      Lactate dehydrogenase activity release into the medium was at low levels (< or =
      5% of the total amount), indicating a good membrane integrity and cell viability.
      The chromosome set (2n = 38) did not change significantly during the first 5 wk,
      but, with additional culture time, the degree of polyploid and polynucleated
      cells increased comparable to the in vivo situation, in which the apical cell
      layer of the bladder mucosa also showed a high degree of polynucleation and
      polyploidy, indicative of a senescence process.

PMID- 8141330
TI  - Endothelin-1 production by rat inner medullary collecting duct: effect of nitric
      oxide, cGMP, and immune cytokines.
AB  - Nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and endothelin-1
      (ET-1) inhibit collecting duct sodium reabsorption. Because the inner medullary
      collecting duct (IMCD) synthesizes NO and ET-1, we examined NO and cGMP
      regulation of IMCD ET-1 production. S-nitroso-N-acetylpenicillamine (SNAP, 6 h)
      increased NO and cGMP and modestly reduced ET-1 release in cultured rat IMCD.
      Atrial natriuretic peptide or dibutyryl cGMP (6 h exposure to each) also mildly
      decreased IMCD ET-1 release. In long-term exposure studies, IMCD cells were
      incubated with tumor necrosis factor (TNF) and interferon-gamma (IFN) up to 72 h.
      IFN/TNF increased NO and cGMP production while reducing ET-1 release by 84%; N
      monomethyl-L-arginine inhibited this effect only marginally, suggesting NO was
      not primarily involved. IFN alone greatly reduced IMCD ET-1 release and ET-1 mRNA
      levels. These data indicate that short- and long-term increases in NO and cGMP
      modestly reduce IMCD ET-1 production. Additionally, IFN potently inhibits IMCD ET
      1 release by an undetermined mechanism.

PMID- 8141332
TI  - X-linked hypophosphatemic Gy mice: renal tubular maximum for phosphate vs. brush
      border transport after low-P diet.
AB  - We examined the effect of the X-linked hypophosphatemic Gy mutation on the
      maximal renal tubular reabsorption of phosphate (TmP) and compared the effects of
      phosphate deprivation on both TmP and Na(+)-dependent phosphate transport in
      renal brush-border membrane vesicles (BBMV). Adult female normal and Gy mice were
      fed a control (1.0% P) or low-phosphate (0.03% P) diet for 5 days. For TmP
      measurement, anesthetized mice were infused intravenously with [3H]inulin and
      increasing increments of phosphate (0, 0.27, 0.54, and 1.08 mumol/min). TmP was
      significantly reduced in Gy mice on the control diet. Normal mice responded to
      the low-phosphate diet by raising their TmP [2.35 +/- 0.12 (n = 9) vs. 3.71 +/-
      0.16 (n = 9) mumol/ml glomerular filtrate, mean +/- SE, P < 0.001], whereas in Gy
      mice, the change was not significant [1.46 +/- 0.10 (n = 10) vs. 1.70 +/- 0.11 (n
      = 10)]. In contrast, Gy mice did respond to phosphate restriction by increasing
      the initial-rate Na(+)-dependent phosphate transport in the renal BBMV [314 +/-
      11 (n = 5) vs. 1,105 +/- 157 (n = 5) pmol.mg protein-1.6 s-1, P < 0.01] as did
      normal mice [583 +/- 64 (n = 5) vs. 1,692 +/- 203 (n = 5) pmol.mg protein-1.6 s
      1, P < 0.01]. In conclusion, the adaptive increase in Na(+)-phosphate cotransport
      in the brush-border membrane of the proximal tubule is not sufficient for the
      overall increase in TmP in the whole kidney in response to dietary phosphate
      deprivation.

PMID- 8141333
TI  - Ionic currents and endothelin signaling in smooth muscle cells from rat renal
      resistance arteries.
AB  - The repertoire of ionic channels expressed in myocytes freshly isolated from
      microdissected interlobar and arcuate arteries of rat kidney and their
      integrative behavior in response to endothelin-1 (ET-1) were studied by
      identification and characterization of major whole cell current components using
      patch-clamp technique. In renal microvascular smooth muscle cells (RMSMC)
      dialyzed with K(+)-containing solution, rapidly inactivating (Ito) and sustained
      outward K+ currents were identified. Voltage-dependent Ito was categorized as "A"
      current based on its kinetics, sensitivity to 4-aminopyridine (4-AP), and
      refractoriness to tetraethylammonium (TEA+). Ca(2+)-activated component of K+
      current was completely blocked by 10 mM TEA+, whereas 5 mM 4-AP did not affect
      this current. Maximal Ca2+ current (ICa) recorded in Cs(+)-loaded RMSMC reached
      250 pA when cells were bathed in a solution with 2.5 mM Ca2+. Two patterns of ICa
      differing in kinetics, voltage range of activation and inactivation, and
      sensitivity to nifedipine were identified as T and L currents. Ca(2+)-dependent
      current component showing reversal potential near Cl- current (ECl) and
      sensitivity to blocking action of 4,4'-diisothiocyanostilbene-2,2'-disulfonic
      acid was identified as Ca(2+)-activated ECl. Activation of RMSMC with ET-1 (1-10
      nM) induced elevation of [Ca2+]i and subsequent activation of Ca(2+)-activated
      ICl, which led to membrane depolarization sufficient to activate voltage-gated
      Ca2+ channels. ET-1-evoked transient reduction of ICa carried through voltage
      gated Ca2+ channels was followed by augmentation of L-type ICa. ET-1-induced
      mobilization of intracellular Ca2+, accompanied by membrane depolarization,
      resulted in activation of Ca(2+)-dependent K+ channels, which can play the role
      of a feedback element terminating ET-1-induced membrane depolarization.

PMID- 8141334
TI  - Characterization of human uroguanylin: a member of the guanylin peptide family.
AB  - Guanylin, a peptide homologue of the bacterial heat-stable enterotoxins (ST), is
      an endogenous activator of guanylate cyclase C (GC-C). We have initiated a search
      for other members of the guanylin peptide family and in the current study
      describe a "guanylin-like peptide" from human urine. Bioactivity was monitored by
      determining the effect of urine extracts on T84 cell guanosine 3',5'-cyclic
      monophosphate (cGMP) levels. Purification yielded two bioactive peaks of peptides
      that, when sequenced by NH2-terminal analysis, possessed 15 and 16 amino acids.
      The sequence of the smaller peptide represented an NH2-terminal truncation of the
      larger peptide. We have termed the larger peptide human uroguanylin; it has the
      following amino acid sequence: NDDCELCVNVACTGCL. Human uroguanylin shares amino
      acid sequence homology with guanylin and ST. Synthetic uroguanylin increased cGMP
      levels in T84 cells, competed with 125I-labeled ST for receptors, and stimulated
      Cl- secretion as reflected by an increased short-circuit current. Thus we report
      the isolation from human urine of a unique peptide, uroguanylin, that behaves in
      a manner similar to guanylin and appears to be a new member of this peptide
      family.

PMID- 8141335
TI  - Effect of angiotensin II on renal arteriolar resistances estimated by
      morphometric analysis.

PMID- 8141336
TI  - Effect of systemic yohimbine on the control of skin blood flow during local
      heating and dynamic exercise.

PMID- 8141337
TI  - Myogenic tone of rabbit facial vein and posterior cerebral artery is influenced
      by changes in extracellular sodium.
AB  - We examined the effect of small changes in extracellular Na+ concentration
      ([Na+]e) on myogenic tone (MT) in isometrically mounted ring segments of the
      rabbit facial vein and in pressurized cannulated posterior cerebral artery
      segments. Decreasing [Na+]e from 150 to 120 mM in the vein increased MT by 24%,
      and raising [Na+]e to 165 mM attenuated it by 30%. In pressurized posterior
      cerebral arteries, decreasing [Na+]e to 120 mM reduced the intraluminal diameter
      by 12%, whereas increasing [Na+]e to 165 mM increased it by 17%. MT was inhibited
      by amiloride [50% inhibitory concentration (IC50) = 17 +/- 6 microM], an
      inhibitor of Na(+)-H+ exchange. Diisothiocyanatostilbene sulfonic acid, a Na(+)
      Cl(-)-HCO3- cotransporter blocker, inhibited MT with an IC50 of 4.4 +/- 0.65
      microM. Ouabain increased MT [50% effective concentration (EC50) = 0.10 +/- 0.04
      microM] as did the reintroduction of HCO3- (EC50 5.0 +/- 1.5 mM). Our study
      suggests that MT in the rabbit posterior cerebral artery and rabbit facial vein
      is modulated by changes in [Na+]e. This effect is independent of the method used
      to register changes in wall force. The sensitivity of the tone to changes in
      [Na+]e and the independence of vessel diameter at different pressures at various
      [Na+]e may reflect changes in the sensitivity of smooth muscle stretch or
      mechanoreceptors to [Na+]e.

PMID- 8141338
TI  - Exogenous intracellular, but not extracellular, iron augments myocardial
      reperfusion injury.
AB  - Although previous studies using iron chelators suggest that iron-catalyzed
      reactions exacerbate myocardial injury, a direct demonstration of the timing,
      sites, and mechanisms of iron-mediated damage during reperfusion has been
      lacking. Catalytic doses of redox-active iron react with exogenously administered
      oxygen radical-generating systems to exacerbate myocardial injury. In an
      analogous manner, catalytic doses (5 microM) of excess iron present during early
      reperfusion should augment oxidative injury, if the redox-active iron is present
      in the same compartment as both the oxygen radicals generated during reperfusion
      as well as the critical biochemical targets of oxidative injury. We determined
      whether catalytic doses of iron given during early reperfusion could exacerbate
      myocardial injury and whether iron-catalyzed injury required intra- or
      extracellular iron. Buffer-perfused rabbit hearts underwent 30 min of 37 degrees
      C global ischemia and 30 min of reperfusion. Iron (5 microM), attached to ligands
      that either restrict iron to the extracellular space (ADP) or facilitate the
      entry of iron into myocytes (omadine, tropolone), was infused during the last 3
      min of ischemia and the first 4 min of reperfusion. Recovery of developed
      pressure was decreased (P < 0.05) in omadine-iron and tropolone-iron compared
      with ADP-iron and noniron hearts treated with ligands alone. Tissue lipid
      peroxide levels, an index of oxidative injury, were increased (P < 0.05) by
      omadine-iron and tropolone-iron, but not ADP-iron. The oxidative damage caused by
      omadine-iron was blocked by pretreatment with dimethylthiourea, a cell-permeable
      scavenger of the hydroxyl radical.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141339
TI  - Effect of endogenous vasopressin on blood flow to choroid plexus during hypoxia
      and intracranial hypertension.
AB  - Exogenous vasopressin decreases blood flow to the choroid plexus and production
      of cerebrospinal fluid. Some studies indicate that hypoxia and increases in
      intracranial pressure (ICP) produce increases in circulating vasopressin. We
      examined the hypothesis that endogenous release of vasopressin decreases blood
      flow to the choroid plexus during hypoxia and increased ICP. Blood flow to the
      choroid plexus was measured in anesthetized rabbits using microspheres. Hypoxia
      increased cerebral blood flow more than twofold but had little effect on blood
      flow to the choroid plexus. In contrast, hypoxia produced a marked increase in
      blood flow to the choroid plexus in the presence of a vasopressin V1-antagonist,
      [d(CH2)5Tyr(Me)]AVP. During intracranial hypertension, blood flow to the choroid
      plexus decreased from 409 +/- 42 to 295 +/- 25 ml.min-1 x 100 g-1 (means +/- SE;
      P < 0.05 vs. control) when ICP was increased from 1 to 40 mmHg. The vasopressin
      antagonist inhibited the decrease in blood flow to the choroid plexus in response
      to increased ICP. Thus release of vasopressin during hypoxia and increased ICP
      have a constrictor effect on blood vessels of the choroid plexus. Plasma levels
      of vasopressin increased minimally during hypoxia and increased ICP, which
      suggests that sources of vasopressin other than plasma affect blood vessels of
      the choroid plexus. We propose that endogenous vasopressin may play a protective
      role during hypoxia and intracranial hypertension by a negative feedback
      mechanism to reduce blood flow to the choroid plexus.

PMID- 8141340
TI  - Effects of vasoactive intestinal peptide on myocardial performance.
AB  - It is now recognized that stimulation of the vagus releases both acetylcholine
      (ACh) and vasoactive intestinal peptide (VIP). Whereas ACh depresses cardiac
      function, recent data indicate that VIP may have a cardiostimulatory effect.
      Exogenously administered VIP appears to enhance left ventricular (LV) contractile
      function; however, whether endogenously released VIP alters LV performance is not
      known. Accordingly, we evaluated the effects of exogenous VIP and endogenously
      released VIP during vagal stimulation after muscarinic and beta-adrenergic
      blockade (VS-B) on LV performance using pressure-volume analysis. Eight
      anesthetized open-chest dogs instrumented to measure LV pressure and volume
      (conductance catheter) were pretreated with atropine (0.1 mg/kg) and propranolol
      (1 mg/kg). The cervical vagi were transected. Hemodynamic data were obtained at
      steady state and during transient vena caval occlusion. Exogenous intravenous VIP
      (0.05 microgram/kg-1 x min-1) increased HR minimally [2.1 +/- 0.9% increase; P =
      not significant (NS)] but significantly increased maximum first time derivative
      of left ventricular pressure (dP/dtmax; 29.4 +/- 19.9% increase; P < 0.05) and
      the slope of the end-systolic pressure-volume relation (Ees; 3.1 +/- 1.3 to 8.9
      +/- 4.2 mmHg/ml; P < 0.05). Minimum first time derivative of left ventricular
      pressure (dP/dtmin) decreased 22 +/- 16.2% (P < 0.05), and the time constant of
      isovolumic relaxation (tau) decreased 38 +/- 18% (P < 0.05). During VS-B (20 Hz,
      15 v, 5 min), HR increased significantly (98 +/- 11 to 130 +/- 26 beats/min; P <
      0.05). Ees also increased significantly (3.3 +/- 1.6 vs. 5.2 +/- 2.8 mmHg/ml; P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141341
TI  - Effect of low perfusate [Ca2+] and diltiazem on cardiac sarcoplasmic reticulum in
      myocardial stunning.
AB  - The ability of low perfusate Ca2+ concentration ([Ca2+]) or diltiazem to improve
      sarcoplasmic reticulum (SR) function and mechanical performance after ischemia
      reperfusion was investigated using an isovolumic Langendorff preparation. SR
      function was evaluated by the oxalate-supported Ca2+ uptake rates of ventricular
      homogenates. Influx of Ca2+ was estimated from the rate of Ca2+ uptake in the
      presence of high concentrations of ryanodine (500 microM) to close the Ca2+
      efflux channel. Ca2+ efflux under the assay conditions was estimated as the
      difference in Ca2+ uptake rate in the presence and absence of ryanodine. Ten and
      fifteen min of global, normothermic ischemia decreased the Ca2+ uptake rate in
      the presence of ryanodine, suggesting that Ca2+ influx was decreased. The effect
      of ischemia on Ca2+ influx was not altered by preperfusion with low [Ca2+] (0.2
      mM) or with 1.0 microM diltiazem. Ischemia decreased SR Ca2+ uptake rate twice as
      much in the absence of ryanodine as in its presence, indicating an increased
      efflux of Ca2+. This increased efflux was reduced by preperfusion with either low
      [Ca2+] or diltiazem. The decreased Ca2+ influx was completely reversed by 15 min
      of reperfusion, whereas the increased Ca2+ efflux was only partially reversed.
      These results indicate that ischemia exerts independent effects on the SR Ca2+
      influx and efflux pathways. The results also suggest that one site of cardiac
      protection by low [Ca2+] or diltiazem is the ryanodine-sensitive Ca2+ efflux
      pathway of the SR, rather than the Ca2+ influx pathway.

PMID- 8141342
TI  - Circulating neutrophil kinetics during tolerance in hemorrhagic shock using
      bacterial lipopolysaccharide.
AB  - The objective of this study was to investigate mechanisms by which circulating
      polymorphonuclear neutrophils (PMNs) may contribute to the tolerance to
      hemorrhagic shock induced by pretreatment with lipopolysaccharides (LPS).
      Tolerance was developed by daily injections of sublethal doses of LPS for four
      subsequent days while controls received saline injections. During shock, both
      groups of rats were maintained for 3 h at 40 mmHg mean arterial pressure and were
      then observed for survival during a 24-h period. This protocol resulted in 40%
      survival in the untreated controls and 89% survival in the tolerant group (P <
      0.0068). Hypotension caused an initial neutropenia in both groups. The
      circulating PMN counts remained lower in the tolerant than in the controls rats
      for most of the low flow period. The number of circulating activated PMNs in
      whole blood, as assessed by spontaneous nitroblue tetrazolium reduction, was
      lower in tolerant animals before and during most of the hypotensive period,
      except immediately after bleeding when both groups have low circulating leukocyte
      counts. No detectable tumor necrosis factor activity was observed in the plasma
      of either group. Adhesion of circulating PMNs to nylon fibers in vitro and the
      number of PMNs adhering to the endothelium in the mesentery in vivo was
      significantly lower in the tolerant rats. We conclude that LPS pretreatment
      produces a reduction in the activated circulating PMNs and in the degree of PMN
      adhesion to endothelium with subsequent improvement of survival after hemorrhagic
      shock.

PMID- 8141343
TI  - Conversion of big ET-1 in the rat lung: role of phosphoramidon-sensitive
      endothelin-1-converting enzyme.
AB  - We examined conversion of Big endothelin-1 (ET-1) to mature ET-1 and pressor
      action during perfusion of the isolated perfused rat lung with Big ET-1. Big ET-1
      caused a concentration-related increase in perfusion pressure and the pressor
      molar potency of the peptide was fivefold less than that of ET-1. Pressor
      responses to Big ET-1 were accompanied by an increase in immunoreactive-ET (IR
      ET) levels in the perfusate and in the lung tissues. Pretreatment with
      phosphoramidon (10(-4) M), a metalloproteinase inhibitor, markedly suppressed the
      pressor action and increment in IR-ET in the tissues. Unexpectedly, the amount of
      IR-ET in the perfusate during perfusion of Big ET-1 was not influenced by
      phosphoramidon treatment. On the other hand, chymostatin, an inhibitor of
      chymotrypsin-like enzymes, effectively suppressed IR-ET levels in the perfusate;
      however, this enzyme inhibitor was without effect on the pressor action of Big ET
      1 or on the increase in IR-ET levels in lung tissues. We tentatively conclude
      that the phosphoramidon-sensitive conversion of Big ET-T to ET-1 is linked to the
      pressor action of Big ET-1 in the isolated perfused rat lung. In addition, it
      seems likely that chymostatin-sensitive conversion of Big ET-1 to ET-1 does not
      play a major role in the conversion of the precursor to the mature form. We
      propose that IR-ET present in the tissues rather than that in the perfusate is a
      better indicator of the functional conversion of Big ET-1 in the rat lung.

PMID- 8141344
TI  - Plasma norepinephrine variations correlate with peripheral vascular resistance in
      resting humans.
AB  - Plasma levels of norepinephrine (NE) vary rhythmically in humans and animals with
      an ultradian (shorter than 1 day) periodicity. We repeatedly measured plasma NE
      levels, blood pressure, cardiac output, and total peripheral resistance in nine
      normal resting subjects over 5 h. Plasma NE correlated with total peripheral
      resistance (Z = 0.322, P < 0.0002) and inversely with cardiac output (Z = -0.276,
      P < 0.0002) for the nine subjects overall. The correlations were strongest in
      subjects with the most spontaneous variability in total peripheral resistance.
      These findings suggest that spontaneous oscillations in plasma NE levels reflect
      alterations in sympathetic nervous activity to resistance blood vessels. The
      negative correlation between cardiac output and plasma NE levels may result from
      the very minor cardiac NE spillover into plasma and the inverse relationship
      between cardiac output and total peripheral resistance.

PMID- 8141345
TI  - Adaptive responses of coronary circulation and myocardium to chronic reduction in
      perfusion pressure and flow.
AB  - We tested the hypothesis that chronic reduction in perfusion pressure and flow in
      the coronary circulation induces a state of myocardial "hibernation"
      characterized not only by a steady-state reduction in myocardial O2 consumption
      (MVO2) but also by evidence of persistent dilator reserve of the distal
      vasculature. Biochemical and morphological changes in the coronary vasculature
      were also assessed. Experiments were conducted in swine with an extraluminal
      coronary stenosis placed 4-32 wk before study. Stenosis reduced lumen diameter by
      approximately 80% at the time of final experimentation. Baseline, regional
      myocardial blood flow distal to the stenosis in both endocardial and epicardial
      layers was reduced vs. that of the normal zone. Vasodilator reserve persisted in
      both endocardial and epicardial layers of the stenosis zone. Flow increased in
      each layer in response to adenosine plus phenylephrine and failed to decline
      despite a marked reduction in perfusion pressure in response to adenosine alone.
      Regional MVO2 at baseline was reduced vs. historical controls without coronary
      stenosis. Protein synthesis rate in coronary vessels of the stenosis zone was
      reduced vs. that of the normal zone. Morphological responses of stenosis zone
      vessel walls were heterogeneous. Smaller microvessels exhibited mild hypertrophy
      of their walls, whereas walls of larger microvessels tended to atrophy. Thus
      chronic reduction in perfusion pressure and flow induces a state of myocardial
      hibernation characterized by a steady-state reduction in MVO2 in association with
      persistent dilator capacity. Biochemical and morphological changes occur in
      microvessel walls and may contribute to observed physiological responses.

PMID- 8141346
TI  - Autoregulation of cochlear blood flow in guinea pigs.
AB  - Autoregulation of blood flow in the inner ear following uncontrolled changes in
      systemic blood pressure (BP), which was induced by the application of
      pharmacological agents that cause local and/or systemic vascular effects, has
      been reported in previous studies. In the current study, carotid BP was
      systematically manipulated without drugs, while the resulting cochlear blood flow
      (CBF) changes were measured using a laser Doppler flowmeter (LDF). Anesthesized
      guinea pigs were used, and the probe of a LDF was held against the ventral
      posterior portion of the surgically exposed cochlea. A mechanical occluder was
      placed around the descending aorta or the inferior vena cava. BP could be
      elevated or lowered over a wide range and was held stable during 2-min
      occlusions. The mean level (+/- SD) of regulation (% delta CBF/% delta BP) for BP
      changes less than +/- 35% of preocclusion baseline was 0.24 +/- 0.2 (or 0.18 +/-
      0.2 if BP is corrected by subtracting central venous pressure). Significant
      regulation occurred for BP between 20 and 70 mmHg. A demonstration of the
      cochlear origin of the regulatory response was obtained by "pharmacological
      blockade" following topical application of the vasodilator, sodium nitroprusside,
      to the cochlea. In this condition, CBF changed in nearly direct proportion to BP.

PMID- 8141347
TI  - Effects of beta-blockade on neurohumoral responses and neurochemical markers in
      pacing-induced heart failure.
AB  - We investigated neurohumoral profiles and transmitter and neuroenzyme markers of
      cardiac autonomic innervation in control (unpaced) dogs and three groups of dogs
      with pacing-induced heart failure (paced, paced + beta-adrenergic blockade, and
      paced + cardiac denervation). Left ventricular ejection fraction decreased
      significantly and to a comparable extent in all paced groups. Pacing increased
      plasma norepinephrine (NE); increases in NE were not attenuated but instead
      tended to be exaggerated by treatment with propranolol or cardiac denervation.
      Atrial hypertrophy occurred in all paced groups compared with the control group.
      However, atrial and right ventricular hypertrophy were not as pronounced in the
      paced plus cardiac denervation group as in the paced and paced plus propranolol
      groups. Pacing also depleted neuropeptide Y and NE from all heart chambers;
      propranolol treatment did not modify these local tissue changes. Pacing caused
      selective depletion of neuroenzymes predominantly in the left ventricle; again,
      propranolol did little to modify these changes. In this study of paced animals
      with experimentally maintained cardiac dysfunction, failure to modify
      noradrenergic responses with intrapericardial cardiac denervation suggests that
      noncardiac sources contribute predominantly to high plasma NE. Failure to modify
      neurohumoral, neuropeptide, and neuroenzyme responses with beta-antagonist
      suggests this treatment has little practical direct influence on sympathetic
      vasomotor activity or neuronal function in heart failure.

PMID- 8141348
TI  - Influence of endurance exercise training on distribution of vascular adaptations
      in rat skeletal muscle.
AB  - We hypothesized that an exercise training program consisting of treadmill running
      at 32 m/min up a 15% incline, 90 min/day, 5 days/wk for 12-14 wk, would elicit
      vascular adaptation in skeletal muscle of all fiber types in rats. This
      hypothesis was based on previous reports that this intensity and duration of
      training caused increases in oxidative capacity in rat skeletal muscle of all
      fiber types. Skeletal muscle vascular transport capacity was examined with
      measurements of total and regional (radiolabeled microspheres) flow capacity,
      capillary filtration coefficient (CFC), and permeability-surface area product
      (PS) for 51Cr-EDTA in maximally vasodilated (papaverine) hindquarters of control
      (C; n = 25) and exercise-trained (ET; n = 26) rats. CFC was increased in ET
      (0.038 +/- 0.001 vs. 0.030 +/- 0.001 ml.min-1 x mmHg-1 x 100 g-1; P < or =
      0.001). PS was greater in ET than C (7.80 +/- 0.33 vs. 6.39 +/- 0.37 ml.min-1 x
      100 g-1; P < or = 0.01). Citrate synthase activity was increased in the soleus
      (25%; P < or = 0.05), the medial head (35%; P < or = 0.05), and the red portion
      of the long head (45%; P < or = 0.005) but not in the white portion of the long
      head of triceps brachii (P = 0.14) of ET rats. Pressure-flow relationships
      indicate that total flow was greater (P < or = 0.05) in ET hindquarters at all
      perfusion pressures. Regional flow data revealed that increases in flow capacity
      were not evident in muscles composed of all fiber types as predicted.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141349
TI  - Potassium channels are not involved in vasopressin-induced vasodilation in the
      rat lung.
AB  - We have previously observed that arginine vasopressin (AVP)-induced pulmonary
      vasodilation is attenuated by nitric oxide (NO) synthesis inhibition; however,
      blockade of the response is incomplete even at very high doses of the inhibitor.
      Thus it was hypothesized that the remaining vasodilation might be due to release
      of an endothelium-derived hyperpolarizing factor acting to open vascular smooth
      muscle K+ channels. Lungs were isolated from male Sprague-Dawley rats and
      perfused at constant flow with physiological saline solution containing 4%
      albumin. After equilibration, lungs were treated with either glibenclamide (50
      microM), Ba2+ (100 microM), tetraethylammonium (10 mM), or the respective vehicle
      and were then constricted with the thromboxane mimetic U-46619. Upon development
      of a stable degree of vasoconstriction, AVP (2.5 x 10(-9) M) was administered and
      its vasodilator action noted. AVP caused an approximately 60% reversal of U-46619
      vasoconstriction in control lungs, and this response was not affected by any of
      the K+ channel blockers. In contrast, administration of the NO synthesis
      inhibitor N omega-nitro-L-arginine (L-NNA; 300 microM) significantly attenuated
      AVP-induced dilation to approximately 25%. The addition of K+ channel blockers
      did not further diminish the vasodilatory response in L-NNA-treated lungs. In
      conclusion, these results suggest that ATP- and Ca(2+)-sensitive K+ channels are
      not involved in the pulmonary vasodilatory response to AVP.

PMID- 8141350
TI  - Dietary Na and baroreflex modulation of blood pressure and RSNA in normotensive
      vs. spontaneously hypertensive rats.
AB  - Different changes in baroreflex control of the circulation have been postulated
      to play a role in the different blood pressure (BP) effects of dietary sodium in
      normotensive vs. genetically hypertensive rats. We therefore evaluated in young
      Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), with or
      without chronic sinoaortic denervation (SAD), the effects of low, regular, and
      high dietary sodium intake from 4 to 8 wk of age on BP and baroreflex function.
      The latter was assessed by changes in renal sympathetic nerve activity (RSNA) and
      heart rate in response to (de)pressor agents. In SHR, the above range of sodium
      caused a marked change in resting BP, somewhat more in intact (48 mmHg) vs. SAD
      (36 mmHg) rats. In contrast, in WKY this range of sodium intake caused only a
      minor (7 mmHg) change in resting BP of intact WKY but a significant (16 mmHg)
      change in WKY with SAD, mainly due to an increase in BP on high sodium. In intact
      WKY increasing dietary sodium from low to regular to high caused stepwise
      increases in the gain of the RSNA-BP reflex, whereas in intact SHR only an
      increase from low to regular sodium intake increased the gain. After SAD, the
      gain of the RSNA-BP reflex was very low, and no longer affected by dietary sodium
      in either strain. These data suggest that in WKY a sensitization in arterial
      baroreflex control of RSNA prevents a sodium-induced increase in BP.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141351
TI  - Steady-state catecholamine stimulation does not increase cytosolic adenosine in
      canine hearts.
AB  - Myocardial adenosine production increases transiently during the onset of
      catecholamine stimulation; however, there is conflicting evidence regarding
      whether cytosolic adenosine concentrations are increased during sustained steady
      state stimulation. If cytosolic adenosine is not elevated during steady-state
      stimulation, then adenosine produced in the cytosol does not play a role in
      mediating the sustained increase in myocardial blood flow. The purpose of the
      present study was to determine whether cytosolic adenosine concentrations in the
      anesthetized dog heart are increased during steady-state stimulation with
      norepinephrine, epinephrine, and atrial pacing. Regional cytosolic adenosine
      concentrations were assessed by measuring myocardial content of S-adenosyl-L
      homocysteine (SAH) after 20 min of intravenous administration of L-homocysteine
      thiolactone. Excess homocysteine causes myocardial accumulation of SAH at a rate
      dependent on the cytosolic concentration of adenosine. Steady-state metabolic
      stimulation caused more than twofold increases in myocardial blood flow and
      oxygen consumption, but there was no increase in left ventricular content of SAH
      in the stimulation group [6.3 +/- 0.9 nmol/g (SE); n = 6] relative to a parallel
      unstimulated control group (6.4 +/- 0.9 nmol/g; n = 6). The transmural
      distribution of SAH was nearly uniform, and there was no correlation between
      regional measurements of blood flow and myocardial content of SAH or ATP either
      during metabolic stimulation or under control conditions. In separate
      experiments, myocardial ischemia caused fivefold increases in SAH content,
      confirming the sensitivity of the SAH method for increased cytosolic
      adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141352
TI  - Effects of R-56865 on transient inward current, Na(+)-Ca2+ exchange, and Ca2+
      release from SR in cardiac myocytes.
AB  - Voltage-clamp studies were performed on guinea pig ventricular myocytes to
      clarify the action of N-(1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl)-N-methyl-2
      benzothiazo lamine (R-56865), an inhibitor of cardiac glycoside-induced
      arrhythmias. Transient inward current ((Iti)) was induced using low-K+/high-Ca2+
      Tyrode solution. R-56865 (1 mM) was found to abolish I(ti). R-56865 had no
      influence on the peak Ca2+ current, steady-state current during the clamp,
      holding current, or the Ni(2+)-sensitive electrogenic Na(+)-Ca2+ exchange
      current. Fluorescence transients after repolarization (temporally related to the
      I(ti)) were abolished by R-56865 without affecting the fluorescence transients
      during depolarization. In separate experiments, the threshold of Ca2+ release
      from sarcoplasmic reticulum (SR) by the Ca2+ current was found to be unchanged,
      whereas Ca2+ transients (presumably triggered by Ca2+ entry through the Na(+)
      Ca2+ exchanger) were depressed. Our results suggest that R-56865 inhibits
      spontaneous Ca2+ release from the SR when it is mediated by Ca2+ entry through
      the Na(+)-Ca2+ exchanger but that it has no direct effect on the well-known
      "physiological" Ca(2+)-induced Ca(2+)-release mechanism from SR.

PMID- 8141353
TI  - Relation among regional O2 consumption, high-energy phosphates, and substrate
      uptake in porcine right ventricle.
AB  - Changes in phosphate metabolites may play a role in the regulation of myocardial
      oxidative phosphorylation in vivo. We tested the hypothesis that changes in
      phosphate metabolites with increased myocardial oxygen consumption (MVO2) depend
      on the mechanism by which MVO2 is increased. In 17 open-chest pigs, regional MVO2
      of the right ventricular (RV) free wall was increased from control by
      isoproterenol infusion (Iso) and by pulmonary artery constriction (PAC). The
      phosphocreatine-to-ATP ratio (PCr/ATP), which is inversely related to free ADP
      concentration ([ADP]), was determined by 31P-nuclear magnetic resonance (NMR)
      spectroscopy. Regional MVO2 and lactate, glucose, and free fatty acid (FFA)
      uptake were determined in the myocardium directly beneath the NMR coil. Iso and
      PAC increased MVO2 nearly equally, to approximately twice control, but produced
      directionally opposite changes in PCr/ATP: a significant decrease with PAC
      (control 1.52 +/- 0.06, PAC 1.35 +/- 0.06, means +/- SE) but a significant
      increase with Iso (to 1.72 +/- 0.07). Thus increased [ADP] may have stimulated
      oxidative phosphorylation during PAC but could not have done so during Iso. With
      Iso, uptake of FFA was more than three times that with PAC, and the sum of the
      oxygen extraction ratios for lactate, glucose, and FFA was more than double that
      with PAC. Enhanced substrate uptake during Iso may have increased mitochondrial
      NADH, which in turn may have provided an alternative stimulus to the rate of
      oxidative phosphorylation. These results support multifactorial control of RV
      oxidative phosphorylation in vivo.

PMID- 8141354
TI  - Myocardial work load is a major determinant of norepinephrine-induced left
      ventricular dysfunction.
AB  - This study was conducted to determine whether increased myocardial energy demand
      plays a role in norepinephrine (NE)-induced left ventricular (LV) dysfunction. A
      range of arterial pressure-heart rate (P-R) products (myocardial energy demand)
      was produced in both conscious and pentobarbital sodium-anesthetized rabbits with
      the same dose of NE (10 micrograms priming bolus plus 2.5 micrograms.kg-1 x min-1
      for 2.5 h). After NE treatment, LV function was evaluated in vitro and found to
      be markedly diminished in the rabbits that had an elevated P-R product. In
      contrast, LV function was not significantly affected when the P-R product was
      maintained near control levels during NE treatment. In separate experiments,
      rabbit hearts were isolated and exposed to NE (10,000 or 50,000 pg/ml) for 2.5 h
      under low P-R product conditions. These hearts exhibited a dose-dependent
      decrease in LV function that was modest compared with that observed in rabbits
      that had elevated P-R products during in vivo NE treatment. Our results suggest
      that high concentrations of NE may cause modest degrees of LV dysfunction
      independently of increases in myocardial energy demand, but the LV dysfunction is
      exacerbated when myocardial energy demand is elevated.

PMID- 8141355
TI  - Vascular Ca overload produced by vitamin D3 plus nicotine diminishes arterial
      distensibility in rats.
AB  - In humans, aging produces many structural changes in blood vessels, one of the
      most pronounced being arterial calcium overload. Simultaneously arteries become
      increasingly rigid. The slow evolution of the two processes renders it difficult
      to evaluate the importance of vascular calcium overload in the development of
      decreased compliance. To gain insight into this relationship, rapid vascular
      calcium overload was produced by treating young rats with vitamin D3 and
      nicotine. When rats were allowed 16 days or longer to recover from such
      treatment, analysis of plasma parameters revealed no overt toxicity, and growth
      rate was similar to that of controls. Pronounced calcium overload was seen
      primarily in compliance arteries. Changes in systemic arterial compliance,
      characteristic impedance, pulse-wave velocity, and carotid compliance all
      reflected a substantial increase in arterial rigidity. Linear regression analysis
      revealed significant correlations between the various indicators of arterial
      distensibility and arterial calcium content. In conclusion, treatment of young
      rats with vitamin D3 and nicotine may provide a suitable model with which to
      investigate how calcium overload is involved in the induration of compliance
      arteries.

PMID- 8141356
TI  - Effects of wake and sleep stages on the 24-h autonomic control of blood pressure
      and heart rate in recumbent men.
AB  - Fifteen recumbent young health volunteers underwent 24-h beat-to-beat blood
      pressure (BP) and interbeat interval (IBI) recordings to explore the effects of
      wake and polygraphically recorded sleep on the nyctohemeral variations in the
      spectral frequency components of BP and IBI and in the arterial baroreflex
      sensitivity (BRS), independent of the confounding effects of changes in posture
      and physical activity. Spectral analysis of BP and IBI provided markers of
      sympathetic and vagal controls and of arterial BRS. When falling asleep, the low
      frequency (LF) BP and IBI components showed a marked decrease while there was a
      clear-cut increase in the high-frequency (HF) IBI component. In contrast, only a
      slight nighttime rapid eye movement-related arterial BRS increase was observed.
      The final morning awakening induced a pronounced decrease in arterial BRS and the
      HF IBI component while there was a marked rise in the LF BP component. Hence, a
      clear 24-h variation in sympathetic and vagal tone but not in arterial BRS
      persists, independent of changes in activity and position.

PMID- 8141357
TI  - Inhibitory effects of cocaine on Ca2+ transients and contraction in single
      cardiomyocytes.
AB  - The effects of cocaine on the Ca2+ transient responsible for excitation
      contraction coupling were studied in single rat heart cells loaded with the
      fluorescent Ca2+ indicator fura 2. A high-speed imaging technique using a charge
      coupled device as detector and transient image store [O'Rourke et al., Am. J.
      Physiol. 259 (Heart Circ. Physiol. 28): H230-H242, 1990] was used to measure
      cytosolic free Ca2+ concentration ([Ca2+]i) and contraction simultaneously from
      the images of fluorescence. Cardiomyocytes maintained a basal [Ca2+]i of
      approximately 140 nM in presence or absence of cocaine. After electrical field
      stimulation, [Ca2+]i increased to a peak of 498 +/- 25 nM under control
      conditions. This was reduced to a peak [Ca2+]i of 389 +/- 25 nM after treatment
      with 50 microM cocaine. Cocaine also reduced the rate of rise of [Ca2+]i but did
      not affect the time to peak or the half time for resequestration of the released
      Ca2+. The rate and extent of cell shortening was reduced by cocaine in parallel
      with the inhibition of the [Ca2+]i transient. Cocaine had no effect on the half
      time for relaxation. Cocaine did not modify the relationship between contraction
      and the elevation of [Ca2+]i over a range of extracellular Ca2+ concentrations.
      The intracellular pool of Ca2+ releasable by caffeine was also unaffected by
      cocaine. In the presence of the beta-adrenergic agonist isoproterenol, which
      caused a large enhancement of peak [Ca2+]i and contraction, cocaine still
      inhibited both parameters. However, cocaine did not reverse the ability of
      isoproterenol to enhance the rate of Ca2+ reuptake and cell relaxation. Whole
      cell voltage-clamp studies showed that 50 microM cocaine reduced both the Na+
      current (50%) and the Ca2+ current (30%). These data suggest that sarcolemmal ion
      channels are the primary site that, in cardiac muscle, mediate the negative
      inotropic effects and the suppression of [Ca2+]i transients by cocaine.

PMID- 8141358
TI  - Regulation of [Na+]i and [Ca2+]i in guinea pig myocytes: dual loading of
      fluorescent indicators SBFI and fluo 3.
AB  - To investigate the mechanisms regulating intracellular Na+ and Ca2+
      concentrations ([Na+]i and [Ca2+]i, respectively), we monitored both ion
      concentrations simultaneously using fluorescent probes, Na(+)-binding benzofuran
      isophthalate (SBFI) and fluo 3, in unstimulated guinea pig ventricular myocytes.
      After the addition of 500 microM strophanthidin, [Na+]i increased gradually from
      6.6 +/- 0.6 to 20.1 +/- 1.6 mM (mean +/- SE) at 50 min. [Ca2+]i, expressed as the
      percentage change of corrected fluo 3 fluorescence, was kept at the low level
      during the first 20 min and then began to increase to 447 +/- 81% of the control
      at 50 min. The addition of 1 microM hexamethylene amiloride prevented the
      increases in both [Na+]i and [Ca2+]i. The perfusion of Ca(2+)-free solution or 5
      mM Ni(2+)-containing solution suppressed the increase in [Ca2+]i. In cells that
      exhibited spontaneous contractile activities, [Ca2+]i increased further than that
      in quiescent cells, whereas [Na+]i levels were similar. In the presence of 1
      microM ryanodine, both the spontaneous contractile activities and the further
      increase in [Ca2+]i were eliminated. These findings indicated that 1) the pathway
      of Na+ entry was mainly through Na(+)-H+ exchange and that the elevated [Na+]i
      induced Ca2+ entry mediated by the reverse mode of Na(+)-Ca2+ exchange, and 2)
      the entered Ca2+ triggered the ryanodine-sensitive Ca2+ release from the
      sarcoplasmic reticulum, causing the dissociation in the relationship between
      [Na+]i and [Ca2+]i.

PMID- 8141359
TI  - Role of endothelium-derived nitric oxide in stimulation of Na(+)-K(+)-ATPase
      activity by endothelin in rabbit aorta.
AB  - An endothelium-derived factor with the properties of nitric oxide (NO) has
      recently been implicated in the regulation of basal Na(+)-K(+)
      adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To determine
      whether this factor also plays a role in the stimulation of ouabain-sensitive
      (OS) 86Rb uptake by specific agonists, studies were carried out using rabbit
      aortic rings. In endothelium-intact rings incubated for 3 h with Krebs-Henseleit
      solution containing 5.5 mM glucose, endothelin (ET) caused a concentration
      dependent increase in OS 86Rb uptake (maximal increase = 205%, with 100 nM ET).
      Incubation with phenylephrine (Phe; 0.1 and 1 microM) or phorbol 12,13-dibutyrate
      (PDBu; 0.1 microM), under the same conditions, increased OS 86Rb uptake by 128,
      144, and 140%, respectively. Removal of endothelium before incubation decreased
      the ability of ET to stimulate OS 86Rb uptake by 38-45%, but it did not diminish
      the stimulation of OS 86Rb uptake by Phe or PDBu. An increase in the
      concentration of glucose from 5.5 to 44 mM diminished ET-stimulated OS 86Rb
      uptake by 50% in endothelium-intact rings but had no effect on Phe- or PDBu
      induced increases in OS 86Rb uptake. Addition of the NO synthase inhibitor NG
      monomethyl-L-arginine (L-NMMA; 0.3 mM) to the medium decreased ET-stimulated OS
      86Rb uptake by 40%. Guanosine 3',5'-cyclic monophophate (cGMP) formation in
      endothelium-intact rings was also increased (65%) by ET but not by Phe or PDBu.
      The increase in cGMP by ET was totally inhibited by L-NMMA or endothelium
      denudation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141360
TI  - Endothelium-dependent relaxation by angiotensin-converting enzyme inhibitors in
      canine femoral arteries.
AB  - The effects of angiotensin-converting enzyme (ACE) inhibitors on vascular
      reactivity were investigated using isolated canine femoral arteries with and
      without endothelium. N-N-(S)-1-carboxy-3-phenylpropyl-L-alanyl-N-(indan-2
      yl)glycine (M-1; an active metabolite of delapril, a nonsulfhydryl ACE inhibitor)
      and captopril (a sulfhydryl ACE inhibitor, 10(-8) to 10(-5) M) relaxed in a dose
      dependent manner canine femoral arterial rings precontracted with prostaglandin
      F2 alpha in the presence of endothelium only. The endothelium-dependent
      relaxations by M-1 and captopril were completely blocked by methylene blue, an
      inhibitor of soluble guanylate cyclase; NG-monomethyl-L-arginine (L-NMMA), an
      inhibitor of nitric oxide synthesis; and oxyhemoglobin, an inactivator of nitric
      oxide; they were partially blocked by aspirin, an inhibitor of cyclooxygenase and
      were enhanced by superoxide dismutase, a radical scavenger. The inhibitory effect
      of L-NMMA on the relaxations by M-1 and captopril were reversed by a high dose of
      L-arginine. Moreover, a bradykinin antagonist partially inhibited these
      relaxations. These results suggest that endothelium-dependent relaxations by M-1
      and captopril in canine femoral arteries are mediated through the release of both
      prostanoids and endothelium-derived nitric oxide via endogenous bradykinin.

PMID- 8141361
TI  - [Ca2+]i and protein kinase C in vasopressin-induced prostacyclin and ANP release
      in rat cardiomyocytes.
AB  - Exposure of cultured, spontaneously beating rat cardiomyocytes to arginine
      vasopressin (AVP) led to marked increases in the release of prostacyclin (PGI2)
      and atrial natriuretic peptide (ANP). These responses were accompanied by a
      rapid, transient rise of cytosolic free Ca2+ concentration ([Ca2+]i) and of
      membranous protein kinase C (PKC) activity. Ca2+ influx and PKC activity appeared
      to play important but distinct roles in AVP-induced cellular responses, insofar
      as only AVP-induced ANP secretion was abolished by the Ca2+ channel antagonist
      nifedipine, whereas both AVP-induced PGI2 production and ANP release were
      abolished by the PKC inhibitors staurosporine and CGP-41251. The AVP-induced
      increase in [Ca2+]i could also be mimicked with the vasopressin (V1-subtype)
      agonist Octapressin, but not with the V2-agonist 1-desamino-8-D-arginine
      vasopressin, and was fully abolished by the V1-antagonist [d(CH2)5Tyr(Me)]AVP,
      but not by d(CH2)5-D-Leu-VAVP (V1-/V2-antagonist). These results indicate that V1
      vasopressinergic receptors mediate AVP-induced PGI2 production and ANP secretion
      in rat cardiomyocytes and that, whereas both Ca2+ influx and PKC activation are
      required for AVP-induced ANP secretion, AVP-induced PGI2 formation is mainly
      regulated by PKC.

PMID- 8141362
TI  - Endothelium-dependent phosphorylation of vasodilator-stimulated protein in
      platelets during coronary passage.
AB  - Compounds that elevate intraplatelet guanosine 3',5'-cyclic monophosphate (cGMP)
      or adenosine 3',5'-cyclic monophosphate (cAMP) stimulate the phosphorylation of a
      46- to 56-kDa thrombocyte protein designated "vasodilator-stimulated protein"
      (VASP), which is most likely involved in the regulation of adhesion/aggregation.
      We investigated whether endothelium-derived relaxing factor (EDRF)/nitric oxide
      (NO) and prostaglandin I2 (PGI2) affected VASP phosphorylation in washed human
      platelets that were injected into the coronaries of saline-perfused rabbit hearts
      (n = 22) and collected immediately after passage. The endothelial stimulator
      acetylcholine (ACh; 1 microM) significantly increased the concentration of cGMP
      (indicating release of EDRF) and PGI2 in the coronary venous effluent, as well as
      the concentration of cGMP and cAMP in platelets. Phosphorylation state of VASP
      increased from 32.1 +/- 2.9 to 64.8 +/- 2.7%. Inhibition of EDRF/NO synthesis by
      NG-nitro-L-arginine (30 microM) completely abolished the ACh-induced cGMP
      increase, attenuated the cAMP-elevation without affecting PGI2, and caused a 20.5
      +/- 5.8% decrease of the phosphorylation state of VASP. Indomethacin (30 microM)
      virtually abolished ACh-induced increases of PGI2, cAMP (but not cGMP), and
      phosphorylated VASP. These results indicate that both EDRF/NO and PGI2 contribute
      to the regulation of VASP phosphorylation in platelets collected after a single
      coronary passage. Their synergistic inhibitory effects on platelet function may
      thus be mediated by a common effect on target proteins like VASP as well as by a
      secondary increase in cAMP in response to cGMP-elevating compounds such as EDRF.

PMID- 8141363
TI  - Effects of trypsin on cardiac ATP-sensitive K+ channels.
AB  - Treatment with trypsin of the cytoplasmic surface of excised inside-out membrane
      patches from guinea pig ventricular myocytes altered multiple regulatory
      properties of ATP-sensitive K+ (KATP) channels including their sensitivity to
      intracellular ATP (ATPi), intracellular ADP (ADPi), glibenclamide, and
      cromakalim. The single-channel conductance, reversal potential, and inward
      rectification (in the presence of intracellular Mg2+) were unaltered after
      trypsin treatment. KATP channels also remained sensitive to intracellular Ca(2+)
      induced rundown after trypsin treatment (n = 6). The effects of trypsin were not
      prevented by including either 15 mM ATPi (n = 7), 1 mM ADPi (n = 4), or 10 microM
      glibenclamide (n = 4) during exposure to trypsin, suggesting that occupancy of
      these binding sites did not prevent access of trypsin to the proteolytic sites
      responsible for its effects. Treatment of excised membrane patches with 1 mM
      phenylglyoxal (n = 4) or 5 mM glyoxal (n = 4), which cleave polypeptides at
      arginine residues, did not increase the dissociation constant for suppression of
      KATP channels by ATPi. Because trypsin cleaves peptides at both arginine and
      lysine residues, these results suggest that modification of the regulatory
      properties of KATP channels by trypsin may result from proteolytic digestion of
      lysine residues located in cytosolic regions of the channel protein.

PMID- 8141364
TI  - ANG II receptor expression and function during phenotypic modulation of rat
      aortic smooth muscle cells.
AB  - Angiotensin II (ANG II) receptors were investigated in primary cultured rat
      aortic smooth muscle cells (SMC) that expressed either a proliferative phenotype
      (during the growth phase) or a contractile phenotype (at postconfluence). For
      each phenotype, alpha-smooth muscle actin expression, 125I-labeled ANG II
      specific binding, D-myo-inositol 1,4,5-triphosphate [Ins(1,4,5)P3] production,
      and ANG II-mediated increases in intracellular calcium (Cai2+) were studied. In
      both phenotypes, 1) ANG II-specific high-affinity binding (KD 0.5 +/- 0.1 nM and
      Bmax 196 +/- 106 pmol/mg protein in proliferative state, KD 1.5 +/- 0.3 nM and
      Bmax 560 +/- 299 pmol/mg protein in postconfluent state) was entirely inhibited
      by the selective AT1-antagonist losartan as well as by [Sar1,Ala8]ANG II and ANG
      III; 2) the AT2-antagonist CGP 42112A was ineffective, except at very high
      concentrations (> or = 10 microM); 3) the specific binding of ANG II was
      inhibited by guanosine 5'-[gamma-thio]triphosphate; and 4) ANG II induced a
      losartan-sensitive increase in Ins(1,4,5)P3. In postconfluent cultures, ANG II
      elicited a rapid biphasic elevation in Cai2+, which was abolished by losartan,
      whereas in growing cultures, this response was either absent or greatly
      attenuated. It is concluded that AT1-receptors coupled to phospholipase C via a G
      protein are expressed in the proliferative as well as in the contractile SMC
      phenotype and that their coupling to Cai2+ release is impaired in the
      proliferative phenotype. No evidence for AT2-receptor expression during
      phenotypic modulation of SMC was found.

PMID- 8141365
TI  - Regional differences in rabbit atrial repolarization: importance of transient
      outward current.
AB  - Regional differences in rabbit atrial repolarization were investigated using a
      conventional microelectrode technique. A more rapid phase 1 repolarization (lower
      phase 1 amplitude) was seen in the left atrial (LA) roof area compared with the
      right atrial (RA) roof area: 54 +/- 10 vs. 82 +/- 6 mV at 1,000 ms (P < 0.001).
      In addition, action potential duration at 40 mV above the resting potential
      (APD40) was shorter in LA and was associated with a slower phase 3 repolarization
      rate. Furthermore, the recovery time constant of phase 1 amplitude at 500 ms was
      0.9 +/- 0.2 s in LA and 3.5 +/- 1.5 s in RA (P < 0.001). Pacing cycle lengths
      (2,000, 1,500, 1,000, 800, and 500 ms) modulated phase 1 amplitude, APD40, and
      phase 3 rate in both regions. 4-Aminopyridine (4-AP; 1 mM), a selective transient
      outward current (I(to)) blocker, abolished cycle length dependence of the above
      action potential parameters and diminished the differences in
      electrophysiological properties between the two regions. 4-AP also flattened the
      restitution curve of phase 1 amplitude in both regions. In conclusion, the
      findings suggest that the different kinetics of I(to) play an important role in
      regional differences of atrial repolarization.

PMID- 8141366
TI  - Resetting of 24-h sodium and water balance during 4 days of servo-controlled
      reduction of renal perfusion pressure.
AB  - This study examines whether an increase in renal perfusion pressure (RPP) is
      necessary to escape endogenously stimulated Na- and water-retaining mechanisms.
      In seven dogs stimulation was accomplished by a servo-controlled reduction of RPP
      (rRPP) below the threshold for pressure-dependent renin release for 4 days. Oral
      intake was standardized. Plasma renin activity (PRA) rose from 2.5 in controls to
      approximately 5 ng ANG I.ml-1 x h-1 during rRPP days. Plasma aldosterone
      concentration (PAC) increased by approximately 50% only on day 1 of rRPP but fell
      at or below control levels thereafter. The PAC-to-PRA ratio decreased during rRPP
      days. Atrial natriuretic factor (ANF) rose to values three times higher than in
      controls. Mean systemic blood pressure (MABP) rose from 111 +/- 12 in controls to
      142 +/- 14 mmHg on day 4 of rRPP. On day 1 of rRPP 60% of the Na and 24% of the
      water intake were retained. However, after 2-3 days the input-output balance was
      restored but on a higher level of total body Na and total body water (new "set
      point"). Because elevated systemic MABP could not exert direct pressure effects
      on the kidneys due to servo control of rRPP, there must be other factors, e.g.,
      fall in PAC, increase in ANF, and changes in intrarenal hemodynamics and physical
      factors that may have contributed to the resetting of input-output balances
      during rRPP.

PMID- 8141367
TI  - Regulation of intracellular pH in cardiac muscle during cell shrinkage and
      swelling in anisosmolar solutions.
AB  - The effect on intracellular pH (pHi) of exposure to solutions of progressively
      increasing osmolarity from 418 to 620 mosM and to hyposmolar solutions (240 mosM)
      was examined in guinea pig ventricular muscle using ion-selective
      microelectrodes. Exposure of tissue to 418 mosM Tyrode solution (100 mM sucrose
      added) produced an intracellular alkalosis of approximately 0.1 U, whereas
      exposure to 620 mosM solution (300 mM sucrose added) caused an intracellular
      acidosis of approximately 0.1 U. The maximal rate of recovery of pHi from
      acidosis induced by an NH4Cl prepulse increased progressively as extracellular
      osmolarity was raised from 310 to 620 mosM. This suggests that the acidosis
      observed at steady state in 620 mosM solution is not due to inhibition of the
      Na(+)-H+ exchanger. In the presence of 10 microM ryanodine, exposure to 620 mosM
      solution produced a sustained intracellular alkalosis. We suggest that the
      decrease in pHi during exposure to 620 mosM solution is due, at least in part, to
      the acidifying influence of Ca2+ release from the sarcoplasmic reticulum. This
      decrease in pHi is expected to contribute to the negative inotrop reported in
      studies of cardiac contractility in markedly hyperosmolar solutions. There was no
      change in pHi when tissue was exposed to hyposmolar solution. However, the
      maximal rate of recovery of pHi from acidosis was slower in hyposmolar than in
      isosmolar solution, despite a concomitant decrease in the intracellular buffer
      capacity. This suggests that osmotic cell swelling results in inhibition of the
      sarcolemmal Na(+)-H+ exchanger.

PMID- 8141368
TI  - Defective endothelium-mediated control of coronary circulation in conscious dogs
      after heart failure.
AB  - The goal of this study was to determine whether coronary endothelial function was
      altered after pacing-induced heart failure in conscious dogs. Fourteen mongrel
      dogs were chronically instrumented for measurements of systemic hemodynamics,
      left circumflex coronary artery diameter (CD) and blood flow, and for left
      ventricular pacing for 4 wk. Heart failure developed during this pacing regimen
      and was characterized by a significant reduction in arterial pressure, an
      increase in left atrial pressure, a resting tachycardia, a depression of left
      ventricular dP/dt to isoproterenol injection, a significant reduction of the
      slope of the end-systolic pressure-diameter relationship, and all of the
      characteristic clinical signs. During heart failure, the dilation of CD after
      release of a brief coronary artery occlusion, acetylcholine, and arachidonic acid
      was attenuated, whereas prostaglandin (PG) I2- and nitroglycerin-induced
      dilations of CD were unchanged. The coronary blood flow responses to occlusion,
      acetylcholine, and nitroglycerin were depressed, but not to PG. Large coronary
      arteries and microvessels were isolated from normal and failing hearts. Both
      isolated large coronary arteries and microvessels from failing hearts produced
      significantly less nitrite, the immediate metabolite of nitric oxide in aqueous
      solution, than those of normal hearts. Thus endothelium-mediated control of the
      coronary circulation was depressed during heart failure. A decrease in the
      production of nitric oxide-endothelium-derived relaxing factor was most likely
      responsible for this depression.

PMID- 8141369
TI  - A mathematical model of sinus node function: validation by recording of sinus
      node electrograms.
AB  - We have applied a mathematical function to model sinus node recovery after atrial
      pacing at different cycle lengths in 13 autonomically denervated, anesthetized
      canines. This model provides "pure" indexes of sinoatrial conduction and of
      suppression of automaticity. We compared sinoatrial conduction computed from the
      model (SACTc) with sinoatrial conduction measured directly utilizing a catheter
      recording the sinus node electrogram (SACTd) to test the validity of the model.
      We used both the model and the sinus node electrogram to further define events
      after pacing. There was close agreement between SACTc and SACTd with correlation
      coefficients at pacing cycle lengths of 20 and 50% below resting of 0.86 (P <
      0.0001) and 0.78 (P < 0.0001), respectively. We verified that the conventional
      sinus node recovery time is due both to suppression of automaticity and
      prolongation of sinoatrial conduction. Sinoatrial conduction time returned
      rapidly to normal over 1-3 beats, whereas automaticity recovered exponentially
      over 20-40 postpacing intervals. The model accurately describes postpacing
      phenomena and has the potential to provide a useful adjunct to the measurement of
      the sinus node electrogram for assessment of sinus node function in the
      experimental laboratory.

PMID- 8141370
TI  - Exercise training increases total systemic arterial compliance in humans.
AB  - Using a noninvasive technique we have investigated the effect of 4 wk of exercise
      training on total systemic arterial compliance (SAC) in 13 previously sedentary
      young males. SAC is assessed from simultaneous measurements of ascending aortic
      blood velocity using Doppler velocimetry and surrogate estimates of aortic root
      pressure obtained by applanation tonometry of the right carotid artery.
      Subsequent calibration of the pressure waveform is by linear interpolation
      against brachial arterial pressures measured sphygmomanometrically. Exercise
      training increased the overall mean maximum oxygen consumption (VO2 max) by 5.1
      ml.min-1 x kg-1 (95% confidence limits 1.30-8.80, P < 0.01) and decreased mean
      systolic blood pressure by 8.4 mmHg [95% confidence interval (CI) 2.9-13.9, P <
      0.01]. Mean SAC increased by 0.26 units (95% CI 0.10-0.43, P < 0.01) with the
      regional stiffness of the aortic arch (measured echocardiographically using the
      beta-index) showing a complementary decrease of 1.03 (95% CI -2.25-0.19, P <
      0.05). Assuming a logarithmic arterial volume-pressure relationship, we were able
      to dissociate the change in SAC due to the exercise training-induced decrease in
      blood pressure from that due to change in the intrinsic compliance of the
      systemic arteries. Our results indicate that 1) exercise training increases SAC;
      2) that the increase in SAC is greater than that due to changes in blood pressure
      and is likely to include a component due to change in intrinsic arterial
      compliance; and 3) that the induced change in SAC is linearly related to change
      in VO2 max.

PMID- 8141371
TI  - Enhanced postischemic dysfunction selective to subendocardium in conscious dogs
      with LV hypertrophy.
AB  - The effects of a 15-min coronary arterial occlusion (CAO) and reperfusion (CAR)
      for 24 h were compared in 11 normal dogs and in 13 conscious dogs with left
      ventricular (LV) hypertrophy (H) induced by ascending aortic banding, which
      increased the LV weight-to-body weight ratio by 69%. The dogs were studied 2-4 wk
      after recovery from instrumentation for measurement of global LV dynamics and
      regional wall motion. During CAO, heart rate and LV end-diastolic pressure
      increased similarly in both groups; however, LV systolic pressure decreased (-38
      +/- 6 mmHg; P < 0.01) only in LVH. At 1 h of CAR, all measurements of systemic
      hemodynamics and global LV function returned to baseline levels in normal dogs;
      however, sustained depression (P < 0.01) in LV systolic pressure (-18 +/- 4 mmHg)
      and mean velocity of circumferential fiber shortening corrected for heart rate (
      0.17 +/- 0.06) were observed in LVH. The recovery in regional myocardial
      dysfunction was significantly prolonged in the subendocardium (Endo) of LVH,
      e.g., at 1 h of CAR, Endo wall thickening was depressed more in dogs with LVH
      compared with normal dogs (-69 +/- 3% vs. -53 +/- 5%; P < 0.01), but not in the
      subepicardium (Epi). Coronary flow reserve, assessed by intravenous adenosine,
      was depressed in Endo of LVH compared with normal dogs, but not altered further
      by CAR. In conclusion, myocardial stunning after a brief period of CAO in dogs
      with LVH was not enhanced in Epi but was modestly increased in Endo. This
      regional dysfunction was, however, sufficiently powerful to induce modest
      impairment of global LV function.

PMID- 8141373
TI  - Role of carotid sinus baroreflex in attenuating systemic arterial pressure
      variability studied in anesthetized dogs.
AB  - Attenuation of systemic arterial pressure (SAP) variability by the carotid sinus
      baroreflex (CSBR) was quantified in nine anesthetized, vagotomized dogs. SAP
      amplitude spectrum was compared between open-loop [SAPo(f)] and closed-loop
      [SAPc(f)] operation of the CSBR. At 0.002 Hz, SAPc amplitude was 3.5 +/- 2.2 (SD)
      mmHg, and SAPo was 9.6 +/- 3.5 mmHg (P < 0.01). At 0.02 Hz, SAP(c) amplitude was
      2.8 +/- 1.2 mmHg, and SAPo was 4.3 +/- 1.2 mmHg (P < 0.05). At higher
      frequencies, SAPo(f) was indistinguishable from SAPc(f). With the opened CSBR,
      intracarotid sinus pressure (CSP) was pseudorandomly varied, and the resulting
      SAP responses were recorded to determine the transfer function from CSP to SAP
      [HCSP.SAP(f)]. From SAPo(f) and the determined HCSP.SAP(f), we estimated SAP(f)
      if the CSBR was closed [SAPc,est(f)] and compared it with SAPc(f). These two
      spectra were similar in each dog over a frequency range of 0.002-0.15 Hz, the
      differences between SAPo(f) and SAPc(f) being reconcilable with HCSP.SAP(f).
      Although the anesthetized state and vagotomy may have distorted the transfer
      characteristics of the CSBR from those in conscious (with the intact vagi)
      states, the results of the present study indicate that the CSBR attenuated SAP
      variability mainly in a low-frequency range below 0.02 Hz and that this
      attenuation was attributable to the transfer properties of the CSBR.

PMID- 8141372
TI  - Metformin improves cardiac function in isolated streptozotocin-diabetic rat
      hearts.
AB  - The effects of metformin administration were studied in isolated perfused working
      hearts from control and diabetic rats. Control and streptozotocin-treated
      diabetic rats were treated for 8 wk with metformin hydrochloride. Treatment was
      initiated at 350 mg.kg-1 x day-1 and was gradually increased to a dose of 650
      mg.kg-1 x day-1, which was maintained over a 6-wk period. Isolated heart
      performance was assessed under conditions of increasing preload to evaluate the
      performance of each heart to "stress." Hearts from untreated diabetic rats
      exhibited a depressed response to increases in left atrial filling pressures from
      17.5 to 22.5 cmH2O in terms of left ventricular developed pressure, ventricular
      contractility, and ventricular relaxation compared with age-matched untreated
      controls. The diabetic hearts also exhibited a delayed half time to relaxation at
      filling pressures from 15 to 22.5 cmH2O. The function curves were performed at a
      constant heart rate of 300 beats/min. These responses were restored to control
      values in diabetic rats treated with metformin. Metformin treatment did not
      affect the ventricular responses in control rats. Metformin reduced plasma
      glucose levels in the diabetic rats from 24.3 to 14.4 mM without any increase in
      the plasma insulin levels. The diabetic group had higher triglycerides than age
      matched untreated control rats, and metformin administration in diabetic rats
      reduced triglyceride levels to control values but had no effect in control rats.
      In conclusion, metformin administration improves cardiac performance in
      streptozotocin-diabetic rats under conditions of increasing preload.

PMID- 8141374
TI  - Hypercapnic acidosis increases oxygen cost of contractility in the dog left
      ventricle.
AB  - The effect of acidosis on left ventricular (LV) mechanoenergetics was assessed in
      seven excised, cross-circulated dog hearts with the use of the frameworks of the
      contractility index (Emax) and the relationship between myocardial oxygen
      consumption (VO2) and pressure-volume area (PVA; a measure of the LV total
      mechanical energy). Acidosis was stably maintained without hypoxia by
      appropriately mixing CO2 and air in a membrane oxygenator in the coronary
      arterial perfusion circuit. Acidosis [pH: 6.98 +/- 0.09 (SD), PCO2: 91 +/- 25
      mmHg in the coronary arterial blood] decreased Emax by 45 +/- 12% (P < 0.01) and
      PVA by 47 +/- 12% (P < 0.01) at a fixed LV volume. When the preacidosis Emax
      level was restored by Ca2+ infusion during acidosis, unloaded VO2 (the VO2
      intercept of the VO2-PVA relation) exceeded the control value by 19 +/- 17% (P <
      0.05), indicating that acidosis required higher VO2 for nonmechanical activities
      at a matched Emax. Moreover, the oxygen cost of enhanced contractility (the
      incremental ratio of unloaded VO2 to Emax) was 1.53 +/- 0.40 times higher (P <
      0.01) during acidosis than preacidosis. We conclude that acidosis results in LV
      contractile dysfunction accompanied by an increased oxygen cost of contractility.
      This increased energy cost of the excitation-contraction coupling can be
      accounted for by a decreased Ca2+ sensitivity of the contractile proteins during
      acidosis.

PMID- 8141375
TI  - Neural modulation of ventriculoarterial coupling in conscious dogs.
AB  - To investigate the role of autonomic reflexes in stroke-work optimization, we
      studied ventriculoarterial coupling in unanesthetized dogs with the autonomic
      system intact and blocked. Ventricular contractility was quantified by the slope
      of the end-systolic pressure-volume relation, ventricular elastance (Ees).
      Arterial system properties were quantified by the ratio of end-systolic pressure
      to stroke volume, arterial elastance (Ea). The coupling between left ventricle
      and arterial system was expressed by the Ea-to-Ees ratio. Changes in arterial
      blood pressure during nitroprusside or angiotensin II infusion were used to
      elicit reflex-mediated influences on ventriculoarterial coupling. With the
      autonomic system intact, Ees doubled during nitroprusside infusion while Ea
      remained unchanged due to reactive vasoconstrictor forces and tachycardia.
      Consequently, the Ea-to-Ees ratio fell 50% from baseline. Angiotensin II infusion
      increased Ea 46% but did not significantly change Ees, resulting in a 26%
      increase in the Ea-to-Ees ratio. In contrast to ventriculoarterial coupling,
      stroke work was insensitive to changes in afterload, remaining close to its
      theoretical maximum. After autonomic blockade, Ees tended to decrease during
      nitroprusside and increased during angiotensin II infusion in parallel with
      changes in Ea, so that the Ea-to-Ees ratio did not change from baseline as much
      as it did with the autonomic system intact. Again, the left ventricle maintained
      nearly 90% of its maximal stroke work. Thus, over a wide range of afterload,
      stroke work was kept near its theoretical maximum, independent of autonomic
      neural regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141376
TI  - Diminished effect of cAMP on Ca2+ accumulation in skinned fibers of hypertrophied
      rat heart.
AB  - Sarcoplasmic reticulum (SR) Ca2+ uptake is reduced in the hypertrophied
      ventricle. To determine whether events initiated by beta-adrenergic stimulation
      are involved, we compared the effects of adenosine 3',5'-cyclic monophosphate
      (cAMP) on SR Ca2+ uptake between normal and pressure-overloaded hypertrophied
      hearts using saponin-skinned rat left ventricular muscles. Left ventricular
      pressure overload was induced by partial ligation of the abdominal aorta for 4-6
      wk before study. Age-matched normal rats served as controls. Pressure overload
      increased the left ventricular weight-to-body weight ratio 60.8%. The SR was
      loaded by exposing the muscles to 10(-6) M Ca2+ solution; SR Ca2+ release was
      induced by 5 or 25 mM caffeine, and the amount of Ca2+ released from the SR was
      estimated by the area under the caffeine-induced transient contraction.
      Concomitant exposure to 10(-4) M cAMP did not influence caffeine-induced Ca2+
      release in either normal or hypertrophied fibers. When 10(-4) M cAMP was applied
      during the Ca(2+)-loading periods, the amount of Ca2+ accumulated by the SR
      increased in both normal and hypertrophied fibers. However, the extent of
      increase was significantly smaller in hypertrophied fibers than in normal fibers
      [10.9 +/- 1.7 and 27.4 +/- 5.3% in 1 min of Ca2+ loading (P < 0.05), 12.2 +/- 3.2
      and 24.7 +/- 3.8% in 4 min of Ca2+ loading (P < 0.05), respectively]. cAMP (10(
      4) M) shifted the force-pCa relationship to the right similarly in normal and
      hypertrophied muscles, and there was no difference in the force-pCa relationship
      between the two groups either with or without cAMP.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8141377
TI  - Myocardial energy metabolism and morphology in a canine model of sepsis.
AB  - The mechanism responsible for sepsis-induced myocardial depression is not known.
      To determine if sepsis-induced myocardial depression is caused by inadequate free
      energy available for work, we studied myocardial energy metabolism in a canine
      model of sepsis. Escherichia coli-infected (n = 18) or sterile (n = 16) fibrin
      clots were implanted intraperitoneally into beagles. Myocardial function and
      structure was assessed using radionuclide ventriculograms, echocardiograms, and
      light and electron microscopy. The adequacy of energy metabolism was evaluated by
      comparing catecholamine-induced work increases [myocardial O2 consumption (MVO2)
      and rate pressure product (RPP)] with a simultaneously obtained estimate of
      intracellular free energy [phosphocreatine-to-adenosine triphosphate ratio
      (PCr:ATP)] determined by 31P-magnetic resonance spectroscopy. When compared with
      control animals, septic animals had a decrease in left ventricular ejection
      fraction (EF, P < 0.0001) on day 1 and fractional shortening (FS, P < 0.0003) on
      day 2 after clot implantation. On day 2, neither septic nor control animals had
      statistically significant decreases in PCr:ATP, despite catecholamine-induced
      increases in MVO2 and RPP (mean maximal increases in septic animals 135 +/- 31
      and 51 +/- 10%, respectively). Light and electron microscopic findings showed
      that hearts of septic animals, compared with control animals, had a greater
      degree of morphological abnormalities. Thus, in a canine model of sepsis with
      alterations in myocyte ultrastructure and documented myocardial depression
      (decreased EF and FS), intracellular free energy levels (PCr:ATP) were maintained
      despite catecholamine-induced increases in myocardial work (increased MVO2 and
      RPP), suggesting high-energy synthetic capabilities are not limiting cardiac
      function.

PMID- 8141378
TI  - Regulation of native collateral vessel dilation after coronary occlusion in the
      dog.
AB  - The purpose of this study was to examine mechanisms involved in the response of
      native collaterals to coronary occlusion. In anesthetized dogs native collaterals
      were identified as vessels coursing between the left anterior descending and left
      circumflex arteries using fluorescence angiography. After a left anterior
      descending occlusion in 12 dogs, collaterals < 100 microns in diameter
      progressively dilated by 21 +/- 4% (n = 12) 1 min after occlusion and by 39 +/-
      6% 15 min after occlusion. Collaterals > 100 microns in diameter did not dilate
      after coronary occlusion. NG-nitro-L-arginine (1 mg/min intracoronary) caused
      constriction under basal conditions in collaterals < 100 microns but did not
      prevent the dilation of collaterals after occlusion. In contrast, glibenclamide
      (10(-5) M), an inhibitor of ATP-sensitive potassium channels, had no effect on
      baseline diameter of collaterals < 100 microns diameter but completely prevented
      dilation of collaterals after occlusion. We conclude that collaterals are not
      maximally dilated immediately after a coronary occlusion but rather progressively
      dilate for at least 15 min after an occlusion. This dilation of native
      collaterals after an occlusion is not mediated by release of an endothelium
      derived relaxing factor derived from L-arginine but is mediated by activation of
      ATP-sensitive K+ channels.

PMID- 8141379
TI  - Length-dependent modulation of ANG II inotropism in rat myocardium: effects of
      myocardial infarction.
AB  - To determine whether changes in sarcomere length affect the inotropic response of
      the heart to angiotensin II (ANG II) differently in dilated and failing
      myocardium, papillary muscles were removed 2 days after infarction, and the
      effects of ANG II were studied at various muscle lengths. Myocardial infarction,
      which averaged 52% of the left ventricle inclusive of the interventricular
      septum, was characterized hemodynamically by left ventricular failure and right
      ventricular dysfunction. ANG II administration at 100% the muscle length where
      force development is maximal (Lmax) produced a 12% depression of developed
      tension in papillary muscles from noninfarcted ventricles and a 37% decrease in
      developed tension in the viable myocardium of infarcted rats. In contrast, at 85
      and 92.5% Lmax and in the presence of ANG II, control muscles increased active
      tension by 16 and 1.0%, whereas muscles from coronary occluded hearts augmented
      developed tension by 13 and 22%, respectively. In conclusion, ANG II exerted a
      positive inotropic effect on rat myocardium at muscle lengths on the ascending
      limb of the Starling curve but a negative inotropic action at the muscle length
      normally associated with maximum force development. This phenomenon emphasizes
      that hormonal influences on the contractile state of the diseased heart may be
      modulated by the interaction of end-diastolic pressure, sarcomere length, and
      ventricular size and shape.

PMID- 8141380
TI  - Effects of metoprolol on left ventricular function in rats with myocardial
      infarction.
AB  - To study the effect of beta-receptor-blocking agents in an animal model of left
      ventricular (LV) dysfunction, we measured LV performance in vivo and in vitro in
      69 rats with or without metoprolol (M) treatment 3 wk after left coronary
      arterial ligation or sham operation. Rats were divided into six groups including
      control (C) and M noninfarct (C-N and M-N), C and M small infarct (C-S and M-S),
      and C and M large infarct (C-L and M-L). LV function was measured as slope of
      change in systolic vs. diastolic pressure (pressure-function curve) during
      pressor response after administration of a bolus of phenylephrine (5
      micrograms/kg i.v.). Reduction of LV function was noted in C-L compared with C-N
      and C-S (slope of pressure-function curve 3.3 +/- 0.3 vs. 11.0 +/- 1.9 and 11.9
      +/- 2.3, respectively) and in M-L compared with M-N and M-S rats (slope of 5.5 +/
      1.4 vs. 11.3 +/- 2.0 and 12.1 +/- 1.4, respectively). There was no significant
      difference between C and M rats, although there was a trend toward partial
      correction of the pressure-function curves in M-L compared with C-L rats. In
      muscle bath preparations the uninfarcted LV posterior papillary muscle from shams
      and rats with small infarcts showed a dose-related increase in peak rate of
      tension development with isoproterenol stimulation, but this response was lacking
      in both C-L and M-L. Tissue assays showed no change in beta-receptor
      number.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141381
TI  - Coronary pressure-flow relationship and exercise: contributions of heart rate,
      contractility, and alpha 1-adrenergic tone.
AB  - We examined the impeding effects of exercise on coronary blood flow by analyzing
      exercise-induced changes in the pressure-flow relationship during maximal
      coronary vasodilation with adenosine in chronically instrumented dogs and
      assessed the individual contributions produced by heart rate, contractility, and
      alpha 1-adrenergic vasoconstriction. Treadmill exercise that increased heart rate
      from 118 +/- 6 beats/min at rest to 213 +/- 8 beats/min (P < 0.01) decreased
      maximum coronary blood flows by decreasing the slope of the linear part of the
      pressure-flow relationship for coronary pressures > or = 30 mmHg (slopeP > or =
      30) from 12.3 +/- 0.9 to 10.9 +/- 0.9 ml.min-1 x g-1 x mmHg-1 (P < 0.01) and
      increasing the measured coronary pressure at zero flow (P zf,measured) from 12.6
      +/- 1.2 to 23.3 +/- 2.0 mmHg (P < 0.01). Atrial pacing at 200 beats/min caused an
      increase of P zf,measured from 15.0 +/- 1.6 to 18.3 +/- 2.1 mmHg (P < 0.05) with
      no change in slopeP > or = 30. While pacing continued, infusion of dobutamine (20
      micrograms.kg-1 x min-1 i.v.) increased contractility to levels similar to those
      during exercise but caused no significant change in coronary blood flow, as a
      decrease of the slopeP > or = 30 was compensated for by a slight decrease in P
      zf,measured. alpha 1-Adrenergic blockade with intracoronary prazosin (10
      micrograms/kg) did not prevent the exercise-induced increase of P zf,measured but
      abolished the decrease of the slopeP > or = 30. When the increases in heart rate,
      contractility, and alpha 1-adrenergic vasoconstriction were prevented, exercise
      still increased P zf,measured from 15.8 +/- 2.1 to 21.8 +/- 2.6 mmHg (P < 0.05)
      but had no effect on the slopeP > or = 30. This residual increase in P
      zf,measured correlated with the concomitant increase in left ventricular filling
      pressure. In conclusion, exercise-induced decreases of maximum coronary blood
      flow were explained by increases in heart rate, alpha 1-adrenergic
      vasoconstriction, and left ventricular filling pressure, with a minimal
      contribution of contractility.

PMID- 8141382
TI  - Flow pulsation and network structure in mesenteric microvasculature of rats.
AB  - Red cell velocity was measured by a fiber-optic laser-Doppler anemometer
      microscope in microvessels of the mesentery of spontaneously hypertensive rats
      (SHR) and normotensive Wistar-Kyoto control rats (WKY) with high temporal
      resolution. Based on the velocity data, the propagation velocity of flow pulse
      along single microvessels as well as the arteriovenous distributions of the mean
      volumetric flow, the amplitude of flow pulsation, and the phase lag of the flow
      relative to the systemic pressure were analyzed in relationship to the vessel
      wall rheology and the network topology. The propagation velocity was 3.5-134 cm/s
      in arterioles of 12-43 microns in diameter, and it increased with increasing
      diameter. The mean volumetric flow exhibited a power law relationship to the
      vessel diameter, in which the exponents were 3.16 and 3.30 for arterioles and
      3.03 and 2.85 for venules in SHR and WKY, respectively. The exponents for
      arterioles were > 3 (P < 0.1) and different between SHR and WKY (P < 0.12). The
      amplitude of the flow pulsation also varied in a power law with the vessel
      diameter, whose exponents for arterioles were 3.41 and 3.52 for SHR and WKY,
      respectively. The flow phase lag increased gradually with decreasing vessel
      diameter in arterioles and increased comparatively rapidly with increasing vessel
      diameter in venules, which suggests more compliant vessel walls for venules than
      arterioles. The slope of the increase in the flow phase lag with the vessel
      diameter in arterioles of SHR was larger than that for WKY (P < 0.05). This
      difference in the flow phase lag distribution and the difference in the exponent
      of the mean flow rate vs. diameter relationship may reflect that the number of
      small arterioles relative to large ones is reduced in SHR microvasculature
      compared with that in WKY.

PMID- 8141383
TI  - Cardioprotection provided by adenosine receptor activation is abolished by
      blockade of the KATP channel.
AB  - Adenosine agonists and openers of the ATP-sensitive potassium (KATP) channel have
      been reported to limit infarct size (IS). We tested the hypothesis that these
      phenomena are interdependent. Anesthetized swine underwent 60 min of coronary
      artery occlusion and 90 min of reperfusion. Preconditioning was elicited by two
      cycles comprising 10 min of occlusion and 10 min of reperfusion (n = 7 swine). An
      intracoronary infusion of adenosine (Ado; n = 10) or (-)-N6-(2-phenylisopropyl)
      adenosine (R-PIA; n = 7) replaced preconditioning ischemia. KATP channels were
      blocked with sodium 5-hydroxydecanoate (5-HD) in the absence (n = 6) or presence
      (n = 8) of R-PIA. Control pigs (n = 7) received saline vehicle. IS was assessed
      with tetrazolium and normalized as percentage of area at risk. Preconditioning
      resulted in a reduced IS compared with Control (3.9 +/- 1.8 vs. 43.5 +/- 6.9%,
      respectively; P < 0.0005). Ado and R-PIA also reduced IS [21.1 +/- 6.8 (P < 0.01)
      and 11.2 +/- 7.4% (P < 0.005), respectively]. 5-HD alone did not alter IS, but it
      abolished R-PIA-induced cardioprotection (IS 5-HD + R-PIA = 48.6 +/- 13.2%). Thus
      Ado A1-receptor agonists mimicked the cardioprotection of ischemic
      preconditioning. The Ado-induced limitation of IS was abolished by blockade of
      the KATP channel. We conclude that both Ado A1 receptors and KATP channels may be
      involved in ischemic preconditioning.

PMID- 8141384
TI  - Measurement of coronary blood flow velocity in conscious rats.
AB  - This study describes a technique for the continuous recording of coronary blood
      flow velocity (CBV) in conscious unrestrained rats. A pulsed Doppler flow probe
      consisting of a 1-mm2 crystal mounted in a 4-mm suction cup was positioned over
      the left coronary artery of pentobarbital sodium-anesthetized rats. The probe was
      held in place with mild suction and sutured to the surface of the myocardium.
      Probes were connected to a pulsed Doppler flowmeter, which measures Doppler shift
      and provides an index of blood flow velocity. While rats were still anesthetized,
      the measurement of CBV was validated by determining that CBV peaked during
      diastole and increased in parallel with arterial pressure. Phasic CBV signals
      obtained in conscious rats were similar to those observed in anesthetized
      animals. Intravenous infusion of dipyridamole (0.5-3 mg.kg-1 x mg-1) produced a
      dose-dependent increase in CBV and decrease in coronary vascular resistance in
      conscious unrestrained rats 7 days after placement of the probe. Light
      microscopic review of cardiac tissue from instrumented rats revealed minimal
      epicardial reaction (fibrin deposition) restricted to the immediate area of the
      probe without distortion of the coronary architecture, edema, inflammation, or
      necrosis compared with controls. Heart weight-to-body weight ratios of
      instrumented rats were also not different from those of control rats. This study
      describes the first technique by which CBV can be measured continuously in
      chronically instrumented rats.

PMID- 8141385
TI  - Kinetics of sodium uptake in freshwater animals: a comparison of ion-exchange and
      proton pump hypotheses.
AB  - Sodium uptake has been shown to follow saturation kinetics in many freshwater
      species of animals, and in the presence of hydrogen ions uptake appears to show
      competitive inhibition. These characteristics are compatible with the hypothesis
      that uptake occurs via a carrier-mediated exchange of sodium ion for hydrogen
      ion. However, recently it has been shown that in frog skin, sodium uptake is
      driven by an electrogenic pump not directly linked to sodium, and evidence is
      accumulating that a similar pump may occur in other freshwater animals. A
      mathematical model is developed that shows that a proton pump would also produce
      saturation kinetics and mimic carrier-mediated competitive inhibition. It would
      also account for the linkage between sodium influx and efflux observed in several
      species.

PMID- 8141386
TI  - Mechanisms for the tachypneic response to the thromboxane A2 mimetic U-46,619 in
      rabbits.
AB  - These experiments were designed to determine if intravenous infusion of the
      thromboxane A2 mimetic, U-46,619, would elicit tachypnea in the rabbit, and if so
      whether the afferent signal was generated by receptors innervated by myelinated
      or unmyelinated vagal nerve fibers. Intravenous infusion of U-46,619 (0.5
      microgram/kg delivered over 10 s) increased breathing frequency (26%) and right
      ventricular blood pressure (59%) in the anesthetized rabbit (n = 10). Systemic
      arterial blood pressure, heart rate, and tidal volume were unaffected by the
      infusion of U-46,619. When myelinated fiber conduction in the vagus nerve was
      eliminated by bilaterally cooling the nerve to 6 degrees C, the increase in
      breathing frequency was only 5% above baseline levels. The tachypneic response to
      U-46,619 was totally eliminated when both myelinated and unmyelinated fiber
      conduction was abolished by cooling the vagi to 0 degree C. The increase in right
      ventricular blood pressure after U-46,619 infusion was unaffected by vagal
      cooling. Because most (> 80%) of the tachypneic response to U-46,619 was
      eliminated by blockade of myelinated vagal fiber conduction, we conclude that the
      tachypneic response to U-46,619 is mediated mostly by receptors innervated by
      myelinated vagal afferent fibers in the anesthetized rabbit.

PMID- 8141387
TI  - Biphasic brown fat temperature responses to hypothalamic stimulation in rats.
AB  - Low-level electrical stimulation (monophasic square-wave pulses: 15 Hz, 7.0
      microA, 0.5 ms) of the ventromedial hypothalamus (VMH) in anesthetized rats
      produced a decrease (phase 1) in interscapular brown adipose tissue (IBAT)
      temperature that was sustained for as long as the stimulus was applied (2-45
      min). A rise in IBAT temperature (phase 2) occurred only after the stimulation
      had stopped. VMH stimulations ipsilateral and contralateral to a lateral
      hypothalamic (LH) lesion indicated that the phase 1 response required an intact
      LH, and denervation of IBAT showed that both phases required an intact
      sympathetic innervation. Central intracerebroventricular injections of
      amphetamine and dopamine produced decreases in IBAT temperature similar in
      magnitude to the phase 1 response to electrical stimulation of the VMH. This, as
      well as the observation that pimozide blocked phase 1, suggested that
      dopaminergic pathways were responsible for mediating the phase 1 decrease in IBAT
      temperature. The peripheral mechanisms responsible for phase 1 are unknown, but a
      vascular component might explain the unexpected decrease in IBAT temperature seen
      during sustained VMH stimulation.

PMID- 8141388
TI  - Role of serotonin and catecholamines in sympathetic responses evoked by
      stimulation of rostral medulla.
AB  - In halothane-anesthetized, paralyzed rats, single-pulse stimulation of nucleus
      raphe pallidus/obscurus (NR) evoked an inhibition followed by a single wave of
      excitation in 1) the mass discharge of lumbar and splanchnic sympathetic nerves
      (modal onset latencies: LSND 210 +/- 14 ms, SSND 161 +/- 5 ms) and 2) the unit
      activity of lumbar sympathetic vasoconstrictor neurons (LSVNs). Stimulation of
      the rostral ventrolateral medulla (RVL) produced two excitatory responses in
      LSND, SSND, and LSVN units (modal onset latencies: RVL peak I 98 +/- 8 ms for
      LSND and 62 +/- 2 ms for SSND; RVL peak II 210 +/- 15 ms for LSND and 160 +/- 6
      ms for SSND). Most LSVNs received excitatory inputs from both raphe and RVL. NR
      peak was selectively attenuated (76%) by 5,7-dihydroxytryptamine
      [intracisternally (ic), 2-wk] and acute intrathecal (it) methiothepine (10
      micrograms, 69%) or methysergide (40 micrograms, 72%). 6-Hydroxydopamine (2-wk
      ic) produced no effect. Phentolamine (20 micrograms it) or prazosin (20
      micrograms it) reduced RVL peak II by > 94% and attenuated NR peak (phentolamine
      67%, prazosin 46%). Intrathecal kynurenic acid produced proportionately larger
      reduction of RVL peak I than raphe peak or RVL peak II. Our interpretations are
      1) LSVNs receive convergent excitatory inputs from midline raphe, parphyramidal
      area, and RVL, 2) bulbospinal serotonergic neurons mediate most of the
      sympathoexcitation evoked from NR and a portion of RVL peak II, 3) a
      catecholamine probably released by C1 cells mediates most of RVL peak II and a
      portion of the NR response, and 4) RVL peak I is predominantly mediated by an
      excitatory amino acid.

PMID- 8141389
TI  - Strain differences in hypothalamic-pituitary-adrenal activity and stress ulcer.
AB  - Strain differences in stress responsiveness have been previously described, but
      specific components of the hypothalamic-pituitary-adrenal (HPA) axis responsible
      for stress hypo- or hyperactivity have not yet been characterized. This study
      proposed to analyze the effect of restraint stress on different measures of HPA
      function and stress ulcer in stress-ulcer prone Wistar-Kyoto (WKY) and Fisher 344
      (F-344) rats and in the ulcer-resistant Wistar strain. Adult male rats of these
      strains were sham adrenalectomized, adrenalectomized, and adrenalectomized
      replaced with corticosterone pellet. Ten days after surgery, animals were
      subjected to the 2-h ulcerogenic water-restraint stress and killed 2 h later.
      Intact WKY rats had dramatically more ulcers and higher anterior pituitary
      adrenocorticotropic hormone (ACTH) and proopiomelanocortin mRNA levels than the
      other two strains. In WKY rats, adrenalectomy increased ulcer incidence but did
      not affect thymus weight, ACTH content, or hypothalamic corticotropin-releasing
      factor mRNA levels, in contrast to the profound effects of adrenalectomy on these
      parameters in the other strains. Furthermore, corticosterone replacement was
      either without effect or enhanced the effect of adrenalectomy on these parameters
      in WKY rats, while it reversed the effects of adrenalectomy in the other strains.
      These data imply that WKY rats respond to stress with enhanced and prolonged
      changes in peripheral functions that are regulated by glucocorticoids, suggesting
      the presence of impaired efficacy of the glucocorticoid negative feedback on HPA
      function.

PMID- 8141390
TI  - PNMT-containing neurons of the C1 cell group express c-fos in response to changes
      in baroreceptor input.
AB  - The immunocytochemical detection of Fos, the protein product of the immediate
      early gene c-fos, was used as a marker for activated neurons to examine whether
      the C1 neurons in the rat rostral ventrolateral medulla (RVLM) respond to changes
      in baroreceptor afferent activity. After hydralazine-induced hypotension or
      sinoaortic denervation, two treatments that reduce baroreceptor afferent
      activity, numerous Fos-positive neurons were observed in the RVLM. The number of
      Fos-positive neurons in the RVLM was counted in brain stem sections from
      hydralazine-treated rats that had been previously injected with Fluorogold into
      the upper thoracic spinal cord to label spinally projecting RVLM neurons as well
      as stained for phenylethanolamine-N-methyltransferase (PNMT) as a marker of C1
      neurons. The results indicate that approximately 80% of the C1 neurons expressed
      Fos in response to hydralazine injection; this was true of spinally projecting C1
      neurons as well as those C1 neurons that were not labeled with Fluorogold.
      Furthermore, in hydralazine-treated rats, the majority of Fluorogold-labeled Fos
      positive neurons contained PNMT. These results suggest that C1 neurons are
      sensitive to baroreceptor afferent input and support a role of these neurons in
      cardiovascular regulation.

PMID- 8141391
TI  - Measurement of circulating blood volume in vivo after trauma-hemorrhage and
      hemodilution.
AB  - Although cardiac output (CO) and other hemodynamic variables are used to assess
      the adequacy of fluid resuscitation after hemorrhage, it is not known whether
      there is any correlation between restoration of CO and circulating blood volume
      (CBV). To determine this, rats underwent a midline laparotomy (i.e., trauma
      induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg
      until 40% of maximum bleedout volume was returned in the form of Ringer lactate
      (RL). The animals were then resuscitated with four or five times the volume of
      maximum bleedout in the form of RL. CO and hepatocellular function were measured
      using an in vivo hemoreflectometer. CBV was monitored by using in vivo
      indocyanine green clearance. A good correlation between the values of blood
      volume obtained by this method and the 125I-albumin method indicates that the
      indocyanine green method is also a reliable technique for measuring CBV. Results
      indicate that resuscitation after hemorrhage improved the decreased CBV but did
      not restore it to control levels despite the fact that CO was restored and
      central venous pressure was more than doubled. A good correlation between
      depressed CBV and hepatocellular dysfunction was also observed under such
      conditions. Thus measurement of CBV appears to be useful for evaluating the
      adequacy of fluid resuscitation after trauma-hemorrhage and hemodilution.

PMID- 8141392
TI  - Influence of exercise and fiber type on antioxidant enzyme activity in rat
      skeletal muscle.
AB  - These experiments examined the influence of exercise intensity and duration on
      antioxidant enzyme activity in locomotor muscles differing in fiber type
      composition. Nine groups of female Sprague-Dawley rats (age 120 days) exercised 4
      days/wk on a motor-driven treadmill for 10 wk. The impact of three levels of
      exercise intensity (low, moderate, and high: approximately 55, approximately 65,
      and approximately 75% of maximal oxygen consumption, respectively) and exercise
      duration (30, 60, and 90 min/day) was assessed. Sedentary animals served as
      controls. Oxidative capacity in the soleus and white and red gastrocnemius was
      assessed by measurement of citrate synthase (CS) activity, and antioxidant
      capacity was evaluated by assay of total superoxide dismutase, catalase, and
      total glutathione peroxidase (GPX) activities. In all muscles, CS activity
      increased as a function of exercise duration. Furthermore, in the soleus and
      white gastrocnemius, the magnitude of the training-induced increase in CS
      activity was directly related to exercise intensity. In contrast, the peak
      increase in CS activity in the red gastrocnemius was relatively independent of
      exercise intensity. Catalase activity was not increased (P > 0.05) in any muscle
      with training. Training-induced changes in superoxide dismutase and GPX
      activities were muscle specific; specifically, exercise training significantly (P
      < 0.05) increased superoxide dismutase activity in the soleus as a function of
      exercise duration up to 60 min/day. Conversely, training-induced significant (P <
      0.05) increases in GPX activity occurred in red gastrocnemius only; the magnitude
      of the GPX increase was directly related to exercise duration but relatively
      independent of intensity. These data demonstrate that exercise training-induced
      changes in muscle antioxidant enzymes are muscle specific.

PMID- 8141393
TI  - Metabolic influences on satiety in rats receiving parenteral nutrition.
AB  - Food intake is reduced during parenteral nutrition (PN) proportionally to the
      amount of calories or composition of the solution infused. The relative
      importance of infused glucose and lipid, 50 and 30% of PN kilocalories,
      respectively, in reducing food intake during PN was examined. Glycolysis, fatty
      acid oxidation, or both were acutely disrupted with 2-deoxy-D-glucose (2-DG) and
      mercaptoacetate (MA). Rats receiving intravenous infusions of saline or a PN
      solution providing 100% of total daily calories (PN-100) received a single
      intraperitoneal injection of saline, 2-DG, and/or MA during the early light
      phase. 2-DG (1.4 or 2.2 mmol/kg) did not initiate feeding in PN-100 rats,
      although hyperglycemia was evident in all rats 1 h after 2-DG. Food intake of PN
      100 rats after MA (0.4 mmol/kg) was approximately 50% that of control rats. When
      2-DG (1.4 mmol/kg) and MA (0.4 mmol/kg) were administered concomitantly, PN-100
      and control rats consumed the same amount of food. During PN-100, rats appeared
      to be more sensitive to losing metabolic energy derived from lipid than from
      glucose.

PMID- 8141394
TI  - Metabolic response to ambient temperature and hypoxia in sinoaortic-denervated
      rats.
AB  - We tested the hypothesis that the sinoaortic afferents may contribute to normoxic
      thermogenesis and to the magnitude of the hypometabolic response to hypoxia.
      Adult rats were either sinoaortic denervated (SAX; n = 20) or sham operated
      (Sham; n = 20). A few days after the operation, gaseous metabolism [O2 uptake
      (VO2) and CO2 production (VCO2)] was measured with an open-flow system at ambient
      temperatures (Tamb) of 20, 25, 30, and 35 degrees C as the animal was resting
      awake. At thermoneutrality (Tamb 30 degrees C) or higher Tamb there was no
      difference in VO2 or VCO2. Below thermoneutrality, metabolic rate was
      significantly lower in SAX than in Sham animals (-14 and -16% at 20 and 25
      degrees C, respectively). Colonic temperature and arterial PO2 were also slightly
      less, whereas arterial PCO2 and pH, mean arterial pressure, and heart rate did
      not differ significantly between the two groups. Exposure to acute hypoxia (10%
      inspired O2, 20-30 min) at Tamb 20 and 25 degrees C significantly reduced VO2 in
      both groups to a similar value; hence, at either Tamb, the metabolic drop during
      hypoxia in Sham animals was larger than that in SAX animals. Hypercapnia (5% CO2
      breathing) did not change VO2 in either group. We conclude that in the rat at
      Tamb slightly below thermoneutrality, the sinoaortic afferents 1) provide a small
      but significant contribution to normoxic thermogenesis and 2) are not required
      for the manifestation of the drop in metabolism during hypoxia.

PMID- 8141395
TI  - Kinetics of active efflux via choroid plexus of beta-lactam antibiotics from the
      CSF into the circulation.
AB  - To examine the role of the choroid plexus in eliminating organic anions from the
      cerebrospinal fluid (CSF), a kinetic study was performed both in in vivo and in
      vitro experiments using [3H]benzylpenicillin (PCG) as a model compound. In vivo,
      after intracerebroventricular administration, [3H]PCG was eliminated from the CSF
      much more rapidly than [14C]mannitol. Analysis of the elimination clearance from
      the CSF revealed that 12 and 24% of the disappearance of [3H]PCG can be accounted
      for by convective loss at a rate equivalent to CSF turnover, and by diffusional
      loss across the ependymal surface into the brain extracellular space,
      respectively. Approximately two-thirds of [3H]PCG elimination was due to a
      saturable process [Michaelis constant (Km) = 43.0 +/- 17.8 microM, maximum
      velocity (Vmax) = 619 +/- 286 pmol.min-1 x rat-1]. These kinetic parameters
      obtained in vivo were comparable to those determined previously in vitro, i.e.,
      [3H]PCG was accumulated by the isolated rat choroid plexus via an active
      transport mechanism (Km = 58 microM, Vmax = 504 pmol.min-1 x rat-1; H. Suzuki, Y.
      Sawada, Y. Sugiyama, T. Iga, and H. Hanano, J. Pharmacol. Exp. Ther. 242: 660
      665, 1987). Furthermore, other organic anions (probenecid, ampicillin,
      cefodizime, cefotaxime, and ceftriaxone) reduced the transport of [3H]PCG in a
      dose-dependent manner both in vivo and in vitro. A good correlation was observed
      between the log inhibition constant (Ki) values obtained for these ligands in
      vivo and in vitro (r = 0.94, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141396
TI  - Tissue-specific increase in norepinephrine turnover by central interleukin-1, but
      not by interleukin-6, in rats.
AB  - To examine the effects of brain cytokines on the sympathetic nervous system,
      norepinephrine (NE) turnover in peripheral organs (spleen, lung, diaphragm,
      pancreas, heart, liver, kidney, and interscapular brown adipose tissue) was
      assessed after intraperitoneal or intracerbroventricular administrations of human
      recombinant interleukin (IL)-1 beta and IL-6 in rats. An intraperitoneal
      injection of IL-1 (1 microgram/rat) accelerated NE turnover in the spleen, lung,
      diaphragm, and pancreas without appreciable effects in other organs examined.
      When IL-1 was injected intracerebroventricularly at much lower doses (1-100
      ng/rat), a dose-dependent increase in NE turnover was observed in the spleen,
      lung, diaphragm, and pancreas. IL-6 did not affect NE turnover in every organ
      examined, even when it was given at much higher doses, 100 micrograms/rat and 100
      ng/rat for intraperitoneal and intracerebroventricular injections, respectively.
      In contrast to tissue NE turnover, plasma corticosterone level was increased
      after the administration of IL-6 as well as IL-1, regardless of the site of
      administration. These results suggest that central IL-1, but not IL-6, increases
      sympathetic nerve activity in some specific organs, whereas both cytokines are
      effective for adrenocortical activation. A possible role of the sympathetic
      nervous system in physiological and immune responses to central IL-1 was
      discussed.

PMID- 8141397
TI  - Cold acclimation increases carnitine palmitoyltransferase I activity in oxidative
      muscle of striped bass.
AB  - The effect of thermal acclimation on the activity of carnitine
      palmitoyltransferase I (CPT I), the rate-limiting enzyme for beta-oxidation of
      long-chain fatty acids, was determined in oxidative red muscle of striped bass
      (Morone saxatilis) acclimated at 5 or 25 degrees C. As observed in mammalian
      tissues, malonyl-CoA potently inhibited CPT I activity of mitochondria.
      Inhibition by malonyl-CoA required inclusions of both bovine serum albumin (BSA)
      and palmitoyl-CoA in the reaction media. Because BSA binds long-chain fatty acyl
      CoAs, this observation suggests that free fatty acyl-CoAs may disrupt
      mitochondrial membranes and affect the CPT I protein. Cold acclimation increased
      citrate synthase activity 1.6-fold and total CPT activity 2-fold in homogenates
      of red muscle; free carnitine increased 62%, and specific activity of CPT I in
      mitochondria increased 2-fold. No differences were observed between cold- and
      warm-acclimated fish in substrate-binding properties of CPT I at an assay
      temperature of 15 degrees C, as judged by the Michaelis constant (Km) for
      carnitine (0.11 +/- 0.02 vs. 0.13 +/- 0.02 mM) or inhibition of CPT I, as
      determined by the half-maximal inhibition concentration (IC50) for malonyl-CoA
      (0.14 +/- 0.05 vs. 0.09 +/- 0.03 microM). Thermal sensitivity of CPT I (Q10 =
      2.91 +/- 0.12 vs. 3.02 +/- 0.20) and preference of CPT I for different long-chain
      fatty acyl-CoA substrates (16:1-CoA = 16:0-CoA > 18:1-CoA) were not altered by
      thermal acclimation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141398
TI  - Effects of 2-buten-4-olide, an endogenous satiety substance, on plasma glucose,
      corticosterone, and catecholamines.
AB  - Effects of 2-buten-4-olide (2-B4O), an endogenous satiety substance, on levels of
      plasma glucose, corticosterone, and catecholamines were examined in fed,
      conscious, and unrestrained rats. A vascular indwelling catheter was inserted
      into the right atrium of the animal from the jugular vein 1 wk before the
      experiment. Injection of 2-B4O and blood sampling were performed through the
      catheter in an unanesthetized condition. The levels of plasma glucose,
      corticosterone, epinephrine, and norepinephrine increased significantly for 2 h
      after the start of intravenous injection of 2-B4O in a dose-dependent manner. The
      increases in glucose and catecholamines induced by 2-B4O injection were abolished
      by bilateral splanchnicotomy (SPX) but not by pretreatment with anti
      corticotropin-releasing factor (CRF) antibody. The increase in corticosterone was
      abolished not by the SPX but by pretreatment with anti-CRF antibody. These
      findings suggest that 2-B4O, endogenously produced during food deprivation, may
      facilitate sympathoadrenal and hypothalamopituitary-adrenal functions through the
      central nervous system.

PMID- 8141399
TI  - Preference and diet type affect macronutrient selection after morphine, NPY,
      norepinephrine, and deprivation.
AB  - The orexigenic agents morphine, neuropeptide Y (NPY), and norepinephrine (NE) and
      deprivation have been reported to induce selection of specific macronutrients:
      fat, carbohydrate (CHO), CHO, and fat, respectively. We utilized analysis of
      covariance to compensate for the influence of baseline preference on feeding
      induced by six experimental procedures: morphine, NPY, NE, 24 and 48 h food
      deprivation, and chronic dietary restriction. Rats received one of two dietary
      regimens: three macronutrient diets containing CHO, protein, or fat (regimen I)
      and two nutritionally complete diets that were high CHO or high fat (regimen II).
      Baseline preference significantly influenced dietary selection after all six
      experimental procedures studied in regimen I and after NPY, NE, 48 h food
      deprivation, and chronic dietary restriction in regimen II (covariate P < 0.05).
      In both dietary regimens, morphine (5 mg/kg) increased consumption of fat, NPY (5
      micrograms icv) increased selection of CHO, and consumption of all diets was
      induced equally after NE injections (20 micrograms icv). After 24 or 48 h food
      deprivation, animals consumed more fat in regimen I and more CHO diet in regimen
      II. Restricting food intake by 20% increased fat and protein consumption in
      regimen I but had no effect in regimen II. Diet selection is affected by prior
      preference, feeding stimulus, and type of diet choice presented.

PMID- 8141400
TI  - Kinetic evaluation of muscle damage during exercise by calculation of amount of
      creatine kinase released.
AB  - To quantify the extent of muscle alteration during prolonged exercise, the
      release rate of creatine kinase (CK) from striated muscle was measured in six
      horses during a rest period (6 h) and during three exercise tests (15, 30, and 60
      km) at a constant speed of 200 m/min. CK clearance was measured after intravenous
      bolus administration (150 U/kg) of a CK solution obtained from horse muscle. The
      CK steady-state volume of distribution was 0.059 +/- 0.0215 l/kg, the terminal
      half-life was 123 +/- 28 min, and the plasma clearance was 0.36 +/- 0.10 ml.kg-1
      x min-1. After an intramuscular CK administration, the CK systemic availability
      was 74.1 +/- 21.2% and the half time of absorption was 9.4 +/- 5.7 h, indicating
      a slow process for CK transit through the lymphatic system. The CK release rate
      was only significantly increased during the 60-km exercise test. The increase of
      CK plasma activity was observed after a delay of approximately 5 h and peaked
      after the end of the race; the estimated CK release rate was 9.92 +/- 2.62 U.kg-1
      x h-1 over a mean duration period of 65.8 +/- 15.8 h. With the CK activity of
      horse striated muscle taken into account, a 60-km race released a quantity of CK
      corresponding to an equivalent of 18.8 +/- 4.3 g striated muscle. It is concluded
      that the equivalent amount of damaged muscle may be considered as negligible for
      a 60-km test and that only very high plasma CK activity levels (at least higher
      than 10,000 U/l) may provide some evidence of a myolysis.

PMID- 8141401
TI  - Abnormalities in the renal and vascular responses to LBNP in humans with early
      diabetes.
AB  - Plasma atrial natriuretic factor (ANF) concentrations are increased in subjects
      with insulin-dependent diabetes mellitus (IDDM). A potential contribution of ANF
      to the maintenance of abnormalities in renal hemodynamic function has been
      considered but not proven in human diabetic subjects. The aim of these
      experiments was to determine the response of renal blood flow (RBF), glomerular
      filtration rate (GFR), filtration fraction (FF), and urinary sodium excretion
      (UNaV) to a reduction of plasma ANF concentrations induced by application of
      nonhypotensive lower body negative pressure (LBNP) in a group of subjects with
      early, uncomplicated, well-controlled IDDM compared with control subjects.
      Baseline supine measurements before LBNP revealed the diabetic subjects to have a
      significantly higher plasma ANF (31 +/- 2 vs. 24 +/- 2 pg/ml, P = 0.05). GFR
      tended to be higher (118 +/- 11 vs. 104 +/- 9 ml/min) and UNaV tended to be
      depressed (188 +/- 25 vs. 240 +/- 25 mumol/min) despite equal sodium intake, but
      not significantly so. In addition IDDM subjects exhibited significantly lower
      baseline plasma norepinephrine (PNE) concentrations (0.91 +/- 0.20 vs. 1.60 +/-
      0.2 nmol/l, P = 0.03). Forearm vascular resistance (FVR) was not significantly
      different between the two groups (29 +/- 5 vs. 33 +/- 5 units). LBNP induced
      comparable decreases in ANF and central venous pressure (CVP) in both groups. The
      anticipated renal response to ANF reduction (declines in GFR, FF, and UNaV)
      occurred only in the normal control group. The percent decline in GFR (11% vs.
      34.5%, P = 0.01) was markedly attenuated in IDDM subjects. The expected reflexive
      increase in PNE and FVR also did not occur in IDDM subjects.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8141402
TI  - Cardiac hypertrophy and brain natriuretic peptide in experimental hypertension.
AB  - The blood pressure was decreased after chronic treatment with enalapril, MK-954,
      and hydralazine in deoxycorticosterone acetate (DOCA)-salt-induced malignant
      hypertension of spontaneously hypertensive rats (SHR); however, ventricular
      weight and plasma brain natriuretic peptide (BNP) concentration were decreased
      after enalapril and MK-954 but not after hydralazine. The BNP secretory rates
      from the ventricle in enalapril- and MK-954-treated DOCA-salt SHR were decreased
      to approximately 50% of those in untreated DOCA-salt SHR. The BNP secretory rate
      from the ventricle was positively correlated with ventricular weight in untreated
      and treated DOCA-salt SHR. In contrast, acute administration of captopril or MK
      954 did not decrease the BNP secretory rate from the heart. Results suggest that
      the decrease in plasma BNP after enalapril and MK-954 is attributed to a decline
      in the secretion from the ventricle but not from the atrium. The reduction in
      ventricular mass appeared to be related to this decline.

PMID- 8141404
TI  - Duodenal sucrose and glucose infusions enhance suppression by cholecystokinin of
      sham feeding.
AB  - In two experiments I examined whether intraduodenal sucrose and glucose would
      enhance inhibition of sham feeding by cholecystokinin-8 (CCK-8). In the first
      experiment, adult male Sprague-Dawley rats received infusions of 0.88 M (30%,
      wt/vol) sucrose or normal saline at 0.51 ml/min for the first 7.67 min of 30-min
      sham-feeding tests. Tests began 10 min after intraperitoneal injections of saline
      or 0.5, 1, or 2 micrograms/kg CCK-8. When sucrose was infused, all doses of CCK-8
      reduced sham feeding of 0.88 M sucrose by 60% or more, but with saline infusions,
      only the highest dose was effective. In the second experiment, rats received 30
      min infusions of 0.3 M (5.4%) or 0.6 M (10.8%) glucose or equimolar saline at
      0.388 ml/min. Although 1 microgram/kg CCK-8 was ineffective in the absence of
      infusions, it significantly reduced intake in combination with both
      concentrations of glucose and hypertonic (0.6 M) saline. Behavioral observations
      indicated that reductions in intake were attributable primarily to decreased meal
      length and slower intake. These results suggest that an intestinal signal may
      contribute to the previously reported ability of preloads to potentiate CCK
      satiety.

PMID- 8141403
TI  - Renin-angiotensin, arterial blood pressure, and salt appetite in rats.
AB  - Simultaneous administration of the diuretic furosemide (10 mg/kg sc) and a low
      dose of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg sc)
      reduced mean arterial blood pressure (MAP) and increased ingestion of water and
      0.3 M NaCl within 2 h. Administration of either agent alone did not reduce MAP or
      cause significant fluid intakes. The increased ingestion of water and saline
      after furosemide plus captopril 1) was not due to increased excretion of water
      and sodium compared with losses after furosemide alone, 2) was abolished by the
      AT1-receptor blocker, losartan (10 mg/kg sc), and 3) was abolished by
      administration of a greater dose of captopril (100 mg/kg sc). Intravenous
      infusion of phenylephrine (3-4 micrograms.kg-1 x min-1) prevented the reduction
      in MAP after furosemide plus captopril and blunted the saline intake but not
      water intake. Simultaneous administration of the vasodilator minoxidil and
      captopril also stimulated robust salt appetite in association with reduced MAP.
      It is concluded that the integrity of renin-angiotensin mechanisms is necessary
      for the rapid ingestion of water and saline after furosemide and captopril and
      that arterial pressure modulates the behavioral responses.

PMID- 8141405
TI  - Monoamine concentrations in cerebrospinal fluid of fetal and newborn sheep.
AB  - Monoamine concentrations were measured in cisternal cerebrospinal fluid (CSF) of
      unanesthetized fetal (115-135 days gestation) and newborn (2-34 days old) sheep.
      Norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations
      decreased with gestational age; NE CSF concentrations were significantly higher
      in the newborn (336.4 +/- 61.7 pg/ml; n = 5) compared with the 131- to 135-day
      gestation fetuses (104.0 +/- 46.3 pg/ml, n = 3; P < 0.05). Dopamine (DO),
      homovanillic acid (HVA), and serotonin (5-HT) concentrations in fetal CSF did not
      change with gestational age, and epinephrine (Epi) was undetectable in most fetal
      and newborn samples. Hypoxia, induced by giving the ewe 9% O2 in N2 to breathe
      for 30 min, resulted in a 10.78 +/- 3.94-fold (n = 5) increase of NE
      concentration in fetal CSF (P < 0.05); DO and DOPAC concentrations did not
      change. Hypoxia did not increase NE concentrations in CSF of newborn lambs.
      Inhibition of prostaglandin (PG) synthesis by intravenous infusion of
      indomethacin significantly reduced plasma prostaglandin E2 concentrations from
      7.8 +/- 1.0 (n = 6) to 2.5 +/- 0.2 nmol/l (n = 3; P < 0.05), and was associated
      with an increase of CSF DOPAC concentrations from 2,156.3 +/- 504.5 (n = 9) to
      5,453.6 +/- 1,091.3 pg/ml (n = 5; P < 0.05); NE and DO concentrations did not
      change significantly. These results show that catecholamines and indoleamines are
      released in the brain and enter the CSF of fetal sheep from at least 115 days
      gestation. The data also show that concentrations of some monoamines in CSF are
      changed by fetal hypoxia or prostaglandin synthesis.

PMID- 8141406
TI  - Insulin acts centrally to enhance reflex tachycardia in conscious rats.
AB  - Systemic and central insulin treatment for 10 days were compared in conscious
      rats given insulin either by daily subcutaneous injection or by continuous
      intracerebroventricular infusion. To measure changes in baroreflex sensitivity,
      heart rate responses elicited reflexly by elevating blood pressure with
      phenylephrine or lowering it with sodium nitroprusside were recorded before and
      after insulin treatment. Although reflex bradycardia and basal mean pressures and
      heart rates were unaffected, reflex tachycardia was consistently more pronounced
      in rats treated with insulin (whether given systemically or centrally) than in
      vehicle-treated controls. Plasma glucose was reduced and plasma insulin was
      elevated but only in insulin-treated rats injected subcutaneously and not in
      those infused intracerebroventricularly. Inasmuch as reflex tachycardia was still
      enhanced when insulin was infused intracerebroventricularly despite the absence
      of hypoglycemia and hyperinsulinemia, our results are compatible with the
      interpretation that insulin acts directly on the brain to enhance reflex
      tachycardia. This interpretation furthermore implies that insulin, even after
      chronic systemic treatment, could reach the brain and alter baroreflex
      regulation.

PMID- 8141407
TI  - Increased potency of carbachol in isolated rat left atria after chronic reserpine
      pretreatment.
AB  - Chronic reserpine pretreatment has been shown to produce postjunctional beta
      adrenergic supersensitivity in cardiac tissue. The present investigation was
      undertaken to determine whether chronic reserpine administration also alters the
      heart's sensitivity to muscarinic cholinoceptor agonists. The direct and indirect
      (antiadrenergic) negative inotropic effects of muscarinic agonists were examined
      in isolated rat left atria at various times after initiation of reserpine
      pretreatment (1.0 mg.kg-1 x day-1 for 7 days). Supersensitivity to the positive
      inotropic effects of isoproterenol was demonstrated at 1, 2, and 3 wk after
      initiation of treatment. Concentration-response curves were then obtained for the
      muscarinic agonist carbachol and the adenosine A1 receptor agonist (-)-N6-(2
      phenylisopropyl)-adenosine (PIA) in reducing the inotropic response to
      isoproterenol (3.16 microM). The potency of carbachol was increased by
      approximately 2.0-fold at 1, 2, and 3 wk. Also, sensitivity to the direct
      negative inotropic effects of carbachol was increased 1.7-fold at 1 wk but not at
      2 and 3 wk. At 1 wk, reserpine pretreatment did not alter either the direct or
      the indirect negative inotropic effects of PIA. These results show that
      postjunctional beta-adrenergic supersensitivity produced by chronic reserpine
      pretreatment is accompanied by a reciprocal increase in sensitivity of isolated
      rat left atria to the negative inotropic effects of muscarinic agonists.

PMID- 8141408
TI  - Role of lateral hypothalamus on fluid, electrolyte, and cardiovascular responses
      to activation of the MSA.
AB  - In this study we investigated the influence of electrolytic lesion or of opioid
      agonist injections into the lateral hypothalamus (LH) on the dipsogenic,
      natriuretic, kaliuretic, antidiuretic, pressor, and bradycardiac effects of
      cholinergic stimulation of the medial septal area (MSA) in rats. Sham- and LH
      lesioned male Holtzman rats received a stainless steel cannula implanted into the
      LH. Other groups of rats had cannulas implanted simultaneously into the MSA and
      LH. Carbachol (2 nmol) injection into the MSA induced water intake, pressor, and
      bradycardic responses. LH lesion reduced all of these effects (1-3 and 15-18
      days). Previous injection of synthetic opiate agonist, FK-33824 (100 ng), into
      the LH reduced the water intake, natriuresis, kaliuresis, and pressor responses
      induced by carbachol injected into the MSA. These data show that both
      electrolytic lesion or injection of an opiate agonist in the LH reduces the fluid
      electrolyte and cardiovascular responses to cholinergic activation of the MSA.
      The involvement of LH with central excitatory and inhibitory mechanisms related
      to fluid-electrolytic and cardiovascular control is suggested.

PMID- 8141409
TI  - Gastric damage and body weight loss in LHA-lesioned rats: effects of
      cytoprotective geranylgeranylacetone.
AB  - We investigated the development of gastric damage and body weight (BW) loss in
      lateral hypothalamic area (LHA)-lesioned rats, measured 2 h and 1 and 3 days
      after the lesioning (experiment 1), as well as the effects of
      geranylgeranylacetone (GGA), a cytoprotective antiulcer agent, on these disorders
      (experiment 2). In experiment 1, BW of LHA-lesioned rats decreased throughout the
      3-day experiment. In LHA-lesioned rats, gastric mucosal lesions appeared 1 day
      after lesioning in the glandular portion and persisted, whereas those in the
      rumenal portion appeared only after 3 days. Gastric transepithelial potential
      differences (PDs) of glandular portion began to decrease after 2 h and had
      decreased in both portions. Gastric acid output was increased transiently at 2 h
      but it was not high after 1 day and after 3 days was lower than that in sham-LHA
      lesioned rats. In experiment 2, PDs of the rumenal decreased more in LHA-lesioned
      rats than in sham-LHA-lesioned rats pair fed to LHA-lesioned rats after 3 days.
      Three days of treatment with GGA (200 mg/kg ip) improved PDs of rumenal and
      glandular portions in LHA-lesioned rats and reduced lesions of the rumenal
      portion. Loss of BW in LHA-lesioned rats was significantly but not completely
      inhibited by GGA. These results indicate that disturbance to the gastric
      defensive mechanism plays an important role in the development of gastric lesions
      after LHA lesions and that the impairment of gastric functions may be a partial
      cause of the loss of BW in LHA-lesioned rats.

PMID- 8141410
TI  - Gustatory deafferentation and desalivation: effects on NaCl preference of Fischer
      344 rats.
AB  - The chorda tympani nerve (CT) appears to be particularly responsive to NaCl
      stimulation of the tongue. However, in most strains of rat, bilateral transection
      of the CT (CTX) results in little alteration of salt preference. The Fischer 344
      (F344) strain of rat is unusual in its lack of preference for any concentration
      of salt. We recently reported a dramatic change from aversion to preference for
      salt in F344 rats after CTX. The present studies further explored this alteration
      in salt preference of F344 rats with an expanded range of NaCl concentrations.
      Additionally, the specificity of the CT in mediating F344 salt aversion was
      examined by testing NaCl preference after glossopharyngeal nerve (GL)
      transections, combined CT and GL deafferentation, and partial desalivation.
      Comparison with Wistar rats revealed that salt preference of F344 CTX rats
      followed a typical preference/aversion pattern across a range of NaCl
      concentrations. Studies of GL section, either alone or combined with CT
      sectioning, indicated that F344 rats' aversion was dependent on the integrity of
      the CT and not the GL. Removal of sublingual and submaxillary salivary glands did
      not lead to preference changes similar to those after CTX, indicating that the
      effects of CTX are not secondary to desalivation. Overall, the findings point to
      signals from the CT as playing a primary role in the NaCl aversion displayed by
      the intact F344 rat.

PMID- 8141411
TI  - Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting
      cerebral metabolism.
AB  - We have previously demonstrated that topical cortical application of nitro-L
      arginine (L-NA), a potent inhibitor of nitric oxide (NO) synthesis, attenuates
      resting cerebral blood flow (CBF) and the cerebrovasodilation elicited by
      hypercapnia. In this study, we sought to determine whether these cerebrovascular
      effects of L-NA are secondary to a depression in cerebral metabolism. Rats were
      anesthetized (chloralose, 80 mg/kg) and artificially ventilated. Arterial
      pressure and blood gases were monitored. The frontal cortex was exposed and
      superfused with normal Ringer (pH 7.3-7.4; 37 degrees C) or with Ringer
      containing L- or D-NA. CBF or cerebral glucose utilization (CGU) was measured
      autoradiographically using the [14C]iodoantipyrine or 2-[14C]deoxy-D-glucose
      method, respectively. Application of normal Ringer did not affect CBF at the site
      of superfusion (n = 5; P > 0.05, paired t test). Application of L-NA (1 mM; n =
      5), but not D-NA (1 mM; n = 6), attenuated resting CBF by 33 +/- 5% (P < 0.05;
      analysis of variance). During hypercapnia (partial pressure of CO2 = 55-60 mmHg),
      L-NA attenuated the CBF increase by 78 +/- 6% (n = 5/group; P < 0.05 from
      Ringer), whereas D-NA had no effect (P > 0.05). Resting CBF and the CBF response
      to hypercapnia were largely unaffected in brain regions outside the field of
      superfusion. In contrast to hypercapnia, L-NA (1 mM) did not attenuate the
      increases in CBF elicited by topical application of papaverine (10-1,000 microM;
      n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141412
TI  - Increase of human platelet serotonin uptake by atypical histamine receptors.
AB  - Histamine and the guanosine 3',5'-cyclic monophosphate (cGMP)-inducing agent
      sodium nitroprusside both increased serotonin (5-HT) uptake and cGMP levels in
      isolated human platelets in vitro. Histaminergic stimulation was observed at
      concentrations ranging from 10 nM to 0.25 microM [mean effective concentration
      (EC50) = 0.1 microM histamine]. The inhibition produced by the H2-receptor
      antagonists tiotidine, metiamide, and cimetidine was 10-10(5) times more potent
      on histamine receptors regulating 5-HT uptake and cGMP generation in human
      platelets than on the histaminergic receptors H1, HIC, H2, and H3 in other
      tissues. The in vitro histamine-induced 5-HT uptake was prevented by
      preincubation of isolated human platelets in the presence of the nitric oxide
      synthase inhibitor NG-monomethyl-L-arginine or the cGMP-lowering agent LY-83583.
      Histamine was ineffective in stimulating cAMP generation in human platelets and
      did not interact with effector sites known to downregulate 5-HT uptake, including
      imipramine, gamma-aminobutyric acid A, peripheral type benzodiazepine-binding
      sites, and V1a vasopressin receptors inducing human platelet shape change and
      aggregation. These atypical human platelet histaminergic receptors differ from
      the previously classified histamine receptors by their apparent high affinity to
      histamine H2-receptor antagonists and their apparent link with the soluble,
      nitric oxide-dependent guanylate cyclase. These findings suggest that human
      platelets express a new subtype H2h of histamine receptors.

PMID- 8141413
TI  - Reflex control of renal sympathetic nerve activity during furosemide diuresis in
      rats.
AB  - To examine the relative role of cardiopulmonary and sinoaortic baroreceptor
      afferents in reflex changes in efferent renal sympathetic nerve activity (ERSNA)
      during furosemide diuresis, ERSNA was measured before and after administration of
      a maximal diuretic dose of furosemide (300 mg/kg iv) in four groups (n = 8 each)
      of pentobarbital sodium-anesthetized rats: animals with intact baroreflexes,
      sinoaortic denervation (SAD), bilateral vagotomy, or SAD plus bilateral vagotomy.
      In addition, measurements of left ventricular end-diastolic pressure (LVEDP),
      mean arterial pressure (MAP), heart rate, and afferent vagal nerve activity were
      performed. Furosemide administration produced an early increase in MAP (+40 mmHg)
      and ERSNA (+50%) that was maintained in rats with SAD plus vagotomy, suggesting
      that this effect is not of sinoaortic or cardiopulmonary baroreflex origin. The
      early pressor response was due to the vehicle, 2% ethanolamine, whereas the early
      renal sympathoexcitation was due to furosemide. Whereas MAP remained unchanged in
      rats with intact arterial baroreflexes, MAP gradually decreased along with a
      reduction in LVEDP during progressive diuresis-related volume depletion in
      animals with SAD. With progressive diuresis-related volume depletion and falling
      LVEDP, ERSNA increased in intact animals (delta ERSNA/delta LVEDP = 46.0 +/-
      1.5%/mmHg). This late increase in ERSNA was inhibited by bilateral vagotomy or
      SAD, suggesting that vagal and sinoaortic baroreceptor afferents are both
      essential for expressing the reflex increase in ERSNA observed during furosemide
      induced volume depletion. There were no significant differences among furosemide
      groups in urinary flow rate and sodium excretion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8141414
TI  - Lesions of hypothalamic PVN partially attenuate stimulatory action of alcohol on
      ACTH secretion in rats.
AB  - We have previously shown that the ability of alcohol to stimulate
      adrenocorticotropic hormone (ACTH) secretion was significantly blunted by
      immunoneutralization of endogenous corticotropin-releasing factor (CRF) and that
      long-term exposure to alcohol increased CRF mRNA levels in the paraventricular
      nucleus (PVN) of the hypothalamus. In the present study, we further investigated
      the participating role of the PVN by studying the effect of bilateral lesions of
      the PVN on alcohol-induced ACTH release. The acute injection of alcohol (1.5 g/kg
      ip) induced significant increases in plasma ACTH levels in sham-operated animals.
      Lesions of the PVN attenuated this response but did not abolish it. Indeed,
      lesioned rats retained significantly elevated ACTH values despite removal of
      secretagogues of PVN origin. Because removal of hypothalamic CRF can alter ACTH
      secretion in response to secretagogues, we studied possible changes in pituitary
      responsiveness to CRF. The results failed to indicate that hyperresponsiveness of
      the corticotrophs played a major role in accounting for the residual ACTH release
      of lesioned rats after alcohol treatment. We conclude that brain regions other
      than the PVN can modulate ACTH release during acute administration of alcohol.

PMID- 8141415
TI  - Orally administered L-arginine does not alter right ventricular hypertrophy in
      chronically hypoxic rats.
AB  - Evidence suggests that nitric oxide synthesis within the pulmonary circulation
      may be attenuated during chronic hypoxia in Wistar rats due to reduced L-arginine
      availability. In contrast, chronically hypoxic Sprague-Dawley rats exhibit normal
      endothelium-dependent pulmonary vasodilation. The purpose of the present study
      was to determine whether 1) Wistar rats demonstrate greater right ventricular
      (RV) hypertrophy in response to chronic hypoxia than Sprague-Dawley rats and 2)
      chronic administration of L-arginine would diminish this response in Wistar rats.
      L-Arginine had no effect on the degree of hypoxia-induced RV hypertrophy or
      polycythemia in either strain of rat. However, Wistar rats demonstrated greater
      hypoxia-induced RV hypertrophy and polycythemia compared with Sprague-Dawley
      rats. To determine whether chronically hypoxic Wistar rats indeed exhibit
      impaired endothelium-dependent pulmonary vasodilation, isolated lungs from
      control and chronically hypoxic Wistar rats were administered the endothelium
      dependent pulmonary vasodilators A23187 or vasopressin. Vasodilatory responses to
      either agent were unaffected by chronic hypoxic exposure. We conclude that
      endothelium-dependent pulmonary vasodilation is maintained in the pulmonary
      circulation of chronically hypoxic Wistar and Sprague-Dawley rats.

PMID- 8141416
TI  - Long-term mineralocorticoid-induced changes in rat neuron properties plus
      interaction of aldosterone and ANG II.
AB  - The central site of action and the neuronal mechanism of the robust sodium
      appetite initiated in rats by the synergistic action of a peripheral priming with
      mineralocorticoid [deoxycorticosterone acetate (DOCA)] and subsequent central
      angiotensin II (ANG II) were investigated using iontophoretic and
      electrophysiological techniques in urethan-anesthetized, DOCA-pretreated (0.5
      mg/day sc for 3 days) or nonpretreated male Wistar rats. A significantly greater
      number of spontaneously active neurons were recorded in the medial septum and
      median preoptic area, but not in the cortex, in rats pretreated with DOCA than
      found in the nonpretreated animals (9.3 +/- 1.2 per electrode descent; n = 19 vs.
      6.1 +/- 0.7 per descent; n = 21; P < 0.001). The firing rate of the spontaneously
      active neurons was also significantly increased in the DOCA-pretreated animals. A
      greatly increased neuronal sensitivity (increased activity lasting up to 10 min
      after the end of the application) to iontophoretically applied ANG II was found
      in 32% of the ANG II-sensitive neurons in pretreated animals. This prolonged
      response was never observed in the nonpretreated animals. Iontophoretically
      applied aldosterone produces rapid neuronal excitation in both groups of rats and
      renders previously insensitive neurons sensitive to iontophoretically applied ANG
      II only in the DOCA-pretreated animals. This forebrain region, therefore,
      contains neurons that undergo a mineralocorticoid pretreatment-induced and/or a
      rapid aldosterone-induced sensitization to ANG II, which may be the neuronal
      mechanism whereby a persistent sodium appetite, induced by the synergistic action
      of these two hormones, is stimulated.

PMID- 8141417
TI  - Atrial natriuretic peptide and glomerular hyperfiltration during onset of
      spontaneous diabetes mellitus.
AB  - The mechanisms responsible for the elevation of glomerular filtration rate (GFR)
      in early stages of insulin-dependent diabetes mellitus (IDDM) are undefined. The
      objectives of this study were to define the temporal pattern of onset of
      glomerular hyperfiltration in the spontaneously diabetes-prone (BB/DP) rat and to
      evaluate the possible role of atrial natriuretic peptide (ANP) as the primary
      mediator of the observed alterations in renal hemodynamics. GFR was significantly
      higher (1.38 +/- 0.07 ml.min-1 x g-1; n = 5) in moderately hyperglycemic BB/DP
      rats (blood glucose > 270 mg/dl) 14 days after the onset of IDDM compared with
      age-matched diabetes-resistant rats (BB/DR), which averaged 1.03 +/- 0.07 ml.min
      1 x g-1 (n = 7). Circulating ANP levels in moderately hyperglycemic BB/DP rats 1,
      7, and 14 days after onset of IDDM were within the normal range, averaging 100 +/
      21, 57 +/- 12, and 65 +/- 6 pg/ml, respectively, and were not significantly
      different (P > 0.05) from ANP levels in age-matched normoglycemic BB/DR rats. To
      further test the role of ANP in glomerular hyperfiltration, an ANP receptor
      antagonist was infused into anesthetized BB/DP rats (n = 10) 14 days after onset
      of IDDM, after baseline measurements of mean arterial pressure, renal
      hemodynamics, and renal fluid and electrolyte excretions. ANP receptor antagonism
      caused a significant reduction in mean arterial pressure from 120 +/- 3 to 103 +/
      2 mmHg; however, there were no significant effects of ANP receptor blockade on
      GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141418
TI  - Effect of acute hypoxia on phosphate excretion in rats.
AB  - This study evaluated the effect of acute hypoxia on renal handling of phosphate
      in rats in the presence and absence of parathyroid hormone (PTH). Hypoxia causes
      respiratory alkalosis in spontaneously breathing humans and animals. Respiratory
      alkalosis has been reported to induce a blunted phosphaturic response to PTH. In
      this study, to avoid the confounding effect of hypocapnia accompanying the
      hypoxia on phosphate excretion, the rats were ventilated mechanically, and
      arterial PCO2 levels were controlled. Rats were divided into two main groups
      depending on the arterial PO2 levels: a hypoxic group (n = 16) and a normoxic
      group (n = 18). Hypoxia was produced by ventilating with 10% oxygen, and
      hypocapnia was produced by hyperventilation. In response to PTH, the hypoxic rats
      without hypocapnia showed a greater increase in fractional excretion of phosphate
      (FEPi; 37.7 +/- 2.6%, mean +/- SE) compared with normoxic rats (27.4 +/- 2.5%, P
      < 0.02). During hypocapnia, there was no difference in FEPi between hypoxic and
      normoxic groups (21.2 +/- 1.5 and 19.5 +/- 1.2%, respectively), and both groups
      showed a significantly blunted phosphaturic response to PTH compared with
      normocapnia (P < 0.05 and P < 0.01, respectively). Urinary adenosine 3',5'-cyclic
      monophosphate (cAMP) increased similarly after PTH infusion between each group.
      To test whether the phosphaturic effect of PTH in hypoxia and the blunted
      phosphaturic effect of PTH in hypocapnia are due to steps beyond the generation
      of cAMP, the phosphaturic response to cAMP infusion was evaluated in 1) hypoxic
      and normocapnic rats (n = 6), 2) normoxic and normocapnic (control) rats (n = 6),
      and 3) normoxic and hypocapnic rats (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141419
TI  - Blunted effect of ANP on hematocrit and plasma volume in streptozotocin-induced
      diabetes mellitus in rats.
AB  - Atrial natriuretic peptide (ANP) infusion increases hematocrit and decreases
      plasma volume by inducing a transfer of plasma fluid from the vascular to the
      interstitial compartment. Diabetes mellitus is associated with resistance to the
      renal actions of ANP. We explored the possibility that the extrarenal responses
      to ANP may also be altered in the diabetic state by measuring changes in arterial
      pressure and hematocrit during infusion of ANP (1 microgram.kg-1 x min-1 for 45
      min) into anesthetized, acutely nephrectomized rats 2-3 wk after induction of
      diabetes from intravenous streptozotocin (STZ) injection (60 mg/kg). Blood
      glucose was significantly elevated in diabetic rats when compared with control
      and insulin-treated diabetic rats. Arterial pressure during ANP infusion
      decreased similarly in control; diabetic, and insulin-treated diabetic rats (by
      7.6 +/- 1.6, 9.6 +/- 1.9, and 8.2 +/- 2% respectively; all P < 0.002). In control
      rats, hematocrit increased progressively to a maximum value of 9.5 +/- 0.9% as a
      result of the infusion, corresponding to a decrease in plasma volume of 16.3 +/-
      1.3%. In contrast, the ANP-induced increase in hematocrit was markedly blunted in
      diabetic rats (1.6 +/- 0.8%; P < 0.0001 vs. ANP infusion in control rats).
      Reducing the hyperglycemia in diabetic rats by insulin therapy restored the
      increase in hematocrit in response to ANP (8.5 +/- 1.1%; P < 0.0001 vs. ANP
      infusion in diabetic rats and P = NS vs. control rats). ANP infusion increased
      plasma ANP levels to the same extent in the three groups, whereas plasma
      guanosine 3',5'-cyclic monophosphate (cGMP) was significantly less in diabetic as
      compared with control and insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8141420
TI  - Enhanced pressor responses to ICV vasopressin after pretreatment with oxytocin.
AB  - The role of oxytocin (OT) in the modulation of arginine vasopressin (AVP)-induced
      cardiovascular effects within the central nervous system was investigated in
      urethan-anesthetized rats. Intracerebroventricular injection of AVP (1-10 pmol)
      produced dose-dependent increases in mean arterial pressure (MAP) and heart rate
      (HR). These responses were enhanced in rats pretreated 24 h earlier with OT (10
      pmol icv). The enhanced cardiovascular effects of AVP in OT-pretreated animals
      were dose dependent, blocked by the V1 antagonist d(CH2)5Tyr(Me)AVP, not evoked
      by OT alone, and occurred in the absence of changes in basal (nonstimulated) MAP
      and HR. In addition, central administration of AVP in OT-pretreated rats, but not
      in saline-pretreated controls, caused dose-dependent oscillations of the MAP and
      HR responses and, at higher doses, death of the animals. The enhanced
      cardiovascular actions of centrally injected AVP in OT-pretreated rats do not
      appear to be secondary to skeletal muscle contractions or the result of cerebral
      ischemia. Our data point to an interaction between the central oxytocinergic and
      vasopressinergic systems in cardiovascular control.

PMID- 8141421
TI  - Endogenous opioids are differentially involved in appetitive and consummatory
      aspects of sexual behavior of male rats.
AB  - The sexual activity of 40 male Wistar rats was tested weekly in a bilevel test
      chamber to evaluate the involvement of endogenous opioids in the appetitive and
      consummatory aspects of sexual behavior. It has been suggested that the increase
      of the anticipatory level-changing behavior over repeated testing, displayed
      before the introduction of a receptive female, is sexually motivated. Two doses
      of the opioid antagonist naloxone, 1 and 10 mg/kg, prevented the increase of the
      anticipatory level-changing over four repeated tests of sexually experienced rats
      without prior experience in the bilevel test chamber and decreased the number of
      level changes of rats displaying a high number of level changes. Analysis of the
      pattern of inhibition suggested that the lower dose of naloxone may reduce sexual
      reward and that, in addition, the higher dose may block the expression of
      motivation. In contrast, naloxone treatment facilitated the efficiency of the
      sexual performance, with less mounts and intromissions preceding ejaculation and
      a shorter ejaculation latency, implying an inhibitory role of endogenous opioids
      in the neural control of some aspects of sexual performance (e.g., ejaculatory
      threshold). These results suggest that endogenous opioids may increase sexual
      appetite and diminish sexual performance.

PMID- 8141422
TI  - Antipyresis caused by stimulation of vasopressinergic neurons and intraseptal or
      systemic infusions of gamma-MSH.
AB  - Antipyretic properties have been ascribed to arginine vasopressin (AVP), and the
      site where its antipyretic effects are mediated in the brain was identified as
      the ventrolateral septum of the limbic system. In guinea pigs, the majority of
      AVP projections to the septum originate from parvocellular neurons of the
      hypothalamic paraventricular nucleus (PVN). Electrical stimulation of the PVN
      with 10-s trains of current pulses (duration 1 ms, frequency 20 Hz, amplitude 8
      V, current 0.205 +/- 0.017 mA) reduced the febrile response to an intramuscular
      injection of 20 micrograms/kg lipopolysaccharide (LPS from Escherichia coli,
      0111: B4) by 54% compared with unstimulated animals. This reduction in fever by
      electrical PVN stimulation was partly reversed by a simultaneous intraseptal
      microinfusion of the vasopressinergic V1-receptor antagonist
      d(CH2)5[Tyr(Met)2]AVP at a concentration of 10(-5) mol for 6 h with an infusion
      speed of 0.1 microliter/min. We further investigated the effects of intraseptal
      microinfusions or systemic infusions of the gamma-melanocyte-stimulating hormone
      (gamma-MSH), a derivative of the proopiomelanocortin, on LPS-induced fever.
      Intraseptal microinfusions of gamma-MSH at a concentration of 10(-5) mol/l for 6
      h with an infusion speed of 0.1 microliter/min caused a 38% reduction in fever. A
      significantly greater 57% reduction in fever was observed when the intraseptal
      microinfusion of gamma-MSH was combined with electrical stimulation of the PVN
      (for parameters see above). A systemic infusion of 0.261 mumol gamma-MSH for 6 h
      reduced LPS fever to approximately 50% compared with animals infused with vehicle
      (0.9% saline).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141423
TI  - An electrophysiological and morphological study of esophageal motoneurons in
      rats.
AB  - Previous anatomic studies have shown that motoneurons supplying the striated
      musculature of the esophagus form a tightly grouped cluster in the rostral
      portion of the nucleus ambiguus, known as the compact formation. This study,
      conducted in anesthetized rats, presents the first in vivo intracellular and
      extracellular recordings from this group of motoneurons, which were identified by
      antidromic stimulation directly from the esophagus (latency 7-68 ms). The
      motoneurons were silent at rest, and those impaled intracellularly (n = 44)
      showed no respiratory modulation of their membrane potential. Intracellular
      labelling with Lucifer Yellow (n = 3) or Neurobiotin (n = 15) revealed multipolar
      somas with longitudinally oriented dendritic trees mainly confined to the compact
      formation. No axon collaterals were found. When swallowing-like activity was
      induced by muscarine applied to the dorsal medullary surface, the motoneurons
      displayed bursting activity, with the majority of bursts occurring during
      expiration. These results show that antidromic stimulation of esophageal
      motoneurons with an electrode inserted into the esophagus provides a simple way
      of identifying these motoneurons. In the absence of pharmacological stimulation,
      these motoneurons receive no respiratory-modulated synaptic input, in contrast to
      adjacent motoneurons in the semicompact formation (supplying the upper airways),
      which are known to display respiratory activity. However, some synchronization of
      respiratory and swallowing-like activity was observed after pharmacological
      activation of the swallowing pattern generator in the dorsal medulla.

PMID- 8141424
TI  - Postingestive alliesthesia produced by exogenous cholecystokinin and blocked by
      abdominal vagotomy.
AB  - Facial consummatory responses reflecting ingestive and aversive perceptions were
      studied and quantified in rats chronically implanted with oral catheters. A
      gustatory stimulus of 50 microliters of 1.75 M sucrose was injected into the
      mouth every 5 min during 65 min. At 5 min, 2 micrograms/kg exogenous
      cholecystokinin (CCK) was injected intraperitoneally. Typical ingestive facial
      consummatory responses were observed in response to sweet stimuli before the
      load. Aversive consummatory responses were observed in response to sweet stimuli
      after the intraperitoneal exogenous CCK (negative alliesthesia). Control
      intraperitoneal injection of saline was not followed by negative alliesthesia in
      response to sweet oral stimuli. In the last part of the experiment rats were
      vagotomized or underwent sham operation. When the vagotomized rats were again
      subjected to the same gustatory sessions, the intraperitoneal exogenous CCK was
      not followed by negative alliesthesia in response to sweet stimuli, whereas sham
      operated rats presented a strong negative alliesthesia. These results in rats
      suggest that CCK mediates duodenal preabsorptive signal for alimentary
      alliesthesia. They also suggest that the effect is peripheral, with the vagus
      nerve as afferent pathway.

PMID- 8141425
TI  - A method for calculating the distribution of pH in tissues and a new source of pH
      error from the 31P-NMR spectrum.
AB  - The true distribution of the pH in tissues can be determined from the in vivo 31P
      nuclear magnetic resonance (NMR) spectrum by converting the parts per million
      (PPM) axis of the pH responsive resonance to pH using the Henderson-Hasselbalch
      equation. In addition, the intensity axis of the resonance must be divided by the
      derivative of the Henderson-Hasselbalch equation to correct for the nonlinear
      relationship between pH and PPM. This nonlinear relationship causes the apparent
      center of the resonance in PPM to be dependent not only on the center of the pH
      distribution but also on its width and distance from the pKa, where Ka is the
      association constant. Therefore, the pH determined from uncorrected spectra may
      be in significant error, particularly if the pH distribution is distant from the
      pKa and is broad. The method was applied to the isolated perfused Morris hepatoma
      5123C to determine the distribution of intracellular pH (pHi) using resonances
      from two intracellular compounds. The two resonances did not report the same pHi
      unless the spectral data were properly corrected. The method should be of
      interest to anyone interested in pHi.

PMID- 8141426
TI  - Hepatic vagotomy effects on metabolic challenges during parenteral nutrition in
      rats.
AB  - During parenteral nutrition (PN) glucoprivic-induced feeding appeared to be
      neutralized by the oxidation of infused fatty acids. With the use of a latin
      square design, the feeding response to 2-deoxy-D-glucose (2-DG) and/or 2
      mercaptoacetate (MA) was evaluated in male Sprague-Dawley rats with hepatic
      branch vagotomy (HV) or sham operations (SO). Rats received continuous infusions
      of 0.9% saline or PN providing 100% of daily caloric needs (PN-100) for four
      consecutive days. During PN-100, food intake was stimulated by 2-DG in HV rats
      and when fatty acid oxidation was simultaneously inhibited by MA. 2-DG-induced
      hyperglycemia was apparent under all conditions. Lipoprivic-induced feeding and
      increased plasma free fatty acid concentrations were absent in HV rats, whether
      MA was administered alone or with 2-DG. The feeding response to glucoprivic
      challenges is influenced by the relative availability of alternate energy
      sources. The lack of feeding response to 2-DG during PN-100 is mediated by vagal
      input of hepatic fatty acid oxidation status.

PMID- 8141427
TI  - Achalasia. A morphologic study of 42 resected specimens.
AB  - Achalasia is characterized by failure of relaxation of the lower esophageal
      sphincter and absence of progressive peristalsis in the esophageal body. Few data
      are available regarding the morphologic features of achalasia, in particular its
      histologic progression. The esophagi of 42 patients with achalasia treated with
      total thoracic esophagectomy were examined histologically in order to
      systematically identify morphologic features of clinically unresponsive achalasia
      and to determine what could be learned about the disease's evolution. In all
      cases, myenteric ganglion cells within the esophageal body were markedly
      diminished, with 20 specimens having none. Twenty specimens had residual ganglion
      cells in the proximal esophagus, and 15 specimens had a few randomly distributed
      ganglion cells in the mid- and distal portions of the esophagus. Inflammation
      within myenteric nerves, present in all cases, generally consisted of a mixture
      of lymphocytes and eosinophils, occasionally with plasma and mast cells. Focal
      replacement of myenteric nerves by collagen occurred in all cases, and there was
      almost complete replacement in several cases. Actual destruction of the residual
      ganglion cells was not seen. The resected esophagi also shared extramyenteric
      morphologic features. Some features probably stemmed from physiologic
      obstruction, such as muscular hypertrophy, mainly of the muscularis propria (all
      cases), with secondary degeneration and fibrosis (29 cases), and eosinophilia of
      the muscularis propria (22 cases). Other changes, probably resulting from chronic
      stasis of ingested materials in the lumen, included diffuse squamous hyperplasia
      (all cases), lymphocytic mucosal esophagitis (28 cases), lymphocytic inflammation
      of the lamina propria and submucosa with prominent germinal centers (all cases),
      and submucosal periductal or glandular inflammation with complete loss of
      submucosal glands in half of the cases. One patient had high-grade squamous
      dysplasia, and another had superficially invasive squamous cell carcinoma. A
      third group of changes was probably due to previous esophagomyotomy, including
      abnormal gastroesophageal reflux, as shown by pH reflux testing (13 cases) and
      Barrett's mucosa (four cases). In one case of Barrett's there was low-grade
      dysplasia. Clinically unresponsive, surgically resected achalasia has almost
      total loss of ganglion cells, and widespread destruction of myenteric nerves has
      already occurred. The only active component is myenteric inflammation. However,
      it cannot be determined whether this inflammation is a manifestation of ongoing
      nerve destruction or whether it is a secondary phenomenon.

PMID- 8141428
TI  - Peritransplant injury to the myocardium associated with the development of
      accelerated arteriosclerosis in heart transplant recipients.
AB  - Accelerated arteriosclerosis is now the major long-term complication of heart
      transplantation. Defining the risk factors associated with the development of
      accelerated arteriosclerosis will provide not only a means of identifying
      patients at risk for this complication but also clues to the etiology of
      accelerated arteriosclerosis. The purpose of this study was to examine the
      relationship between peritransplant myocardial ischemic injury and the
      development of accelerated arteriosclerosis. In a case-control study we examined
      the first three endomyocardial biopsies from 50 heart transplant recipients and
      graded the degree of ischemic injury present in these biopsies. The histologic
      changes graded in the biopsies included contraction band necrosis, coagulative
      necrosis, and macrophagic removal of ischemically injured myocytes. Of the 50
      recipients included in the study, 25 had angiographic evidence of accelerated
      arteriosclerosis and 25 did not. In multivariate analysis, which included the
      number of class I major histocompatibility (MHC) antigen mismatches between the
      donor and the recipient, the recipient's post-transplant cytomegalovirus status,
      the donor's age, and the number of rejection episodes, the histologic degree of
      ischemic injury present in the biopsies emerged as the strongest predictor of the
      development of accelerated arteriosclerosis (RR 2.6, 95% CI 1.2-5.8, p = 0.02).
      These results suggest that ischemic injury to the heart during the peritransplant
      period significantly contributes to the development of accelerated
      arteriosclerosis in heart transplant recipients and that histologic changes in
      early posttransplant biopsies can be used to identify recipients at risk of
      developing accelerated arteriosclerosis.

PMID- 8141429
TI  - Malignant lymphomas of B-cell lineage with marked tissue eosinophilia. A report
      of five cases.
AB  - Tissue eosinophilia is commonly seen in Hodgkin's disease and non-Hodgkin's
      lymphomas of T-cell lineage. In contrast, eosinophilia is infrequent in non
      Hodgkin's lymphomas of B-cell origin. We describe five-B-cell lymphomas with
      exuberant tissue eosinophils. According to the Working Formulation, three were
      classified as large-cell immunoblastic, one as small lymphocytic lymphoma/chronic
      lymphocytic leukemia, and one as low-grade, not further subclassified, with
      features of monocytoid B-cell lymphoma. Immunophenotypic studies in each case
      revealed B-cell lineage; neoplastic cells expressed monotypic immunoglobulin
      light chain (four of five cases) or pan-B-cell antigens (five of five cases) and
      were negative for T-cell antigens. Southern blot hybridization in one case
      revealed immunoglobulin gene rearrangements, further confirming B-cell lineage.
      Eosinophilopoiesis is stimulated by interleukin 5 (IL-5), and Epstein-Barr virus
      (EBV) has been shown to upregulate IL-5 production. Therefore, both EBV infection
      and IL-5 expression were investigated as possibly pathogenetic mechanisms for the
      eosinophilia. However, both in situ hybridization studies for EBV mRNA and IL-5
      mRNA were negative in the neoplastic cells. In one tumor, IL-5 was abundant in
      the cytoplasm of the eosinophils, a pattern similar to that seen in five cases of
      Hodgkin's disease studied with the same technique. Although rare, marked tissue
      eosinophilia may be associated with B-cell non-Hodgkin's lymphomas.
      Immunophenotypic or molecular genetic analyses are needed to make the correct
      diagnosis.

PMID- 8141430
TI  - Malignant lymphoma of the testis, epididymis, and spermatic cord. A
      clinicopathologic study of 69 cases with immunophenotypic analysis.
AB  - We studied 69 cases of malignant lymphoma of the testis, epididymis, and
      spermatic cord, including 64 cases in which the tumor involved these sites at
      presentation and five cases in which lymphoma relapsed in the testis. The
      patients without prior lymphoma were 16 to 91 (mean, 56) years old. Fifty-two
      patients had diffuse large-cell lymphomas [seven large cleaved cell (two with
      follicular areas), 27 large noncleaved, two multilobated, six not otherwise
      specified (NOS), 10 immunoblastic]; six, small noncleaved cell; two, diffuse
      mixed small and large cell; one, diffuse small cleaved; one, follicular mixed
      small cleaved and large cell; and two, high grade, unclassified in the Working
      Formulation. Twenty-nine cases (55%) were stage I; five (9%), stage II; one (2%),
      stage III, and 18 (34%), stage IV. Forty patients (73%) achieved a complete
      remission; 23 had a relapse of tumor at 4 to 274 months (median, 13) and five
      were salvaged. At last follow-up, 20 (36%) patients were free of disease, six
      (11%) were alive with disease, and 29 (53%) had died of lymphoma. Features
      associated with longer disease-free actuarial survival (DFS) included stage I
      disease (p = 0.0001) and sclerosis (p = 0.0001). Among patients with stage I
      lymphoma, those with right-sided tumors (p = 0.005) or tumors with sclerosis (p =
      0.0017) had longer DFS. Lymphomas with extensive sclerosis were all stage I (p =
      0.0057). Four of five patients with secondary testicular lymphoma had extranodal
      primary sites. They ranged from 13 to 66 years (median, 35). Testicular relapses
      occurred 13-37 months after initial diagnosis. Three had diffuse large,
      noncleaved cell type; one, lymphoblastic and one, diffuse mixed small and large
      cell. Immunophenotyping showed B lineage in 33 cases and T lineage in one case.
      Most testicular lymphomas are B-lineage large-cell lymphomas, which frequently
      involve other extranodal sites at presentation and at relapse, and which often
      have an aggressive clinical course.

PMID- 8141431
TI  - Polysialic acid of the neural cell adhesion molecule in the human thyroid: a
      marker for medullary thyroid carcinoma and primary C-cell hyperplasia. An
      immunohistochemical study on 79 thyroid lesions.
AB  - We recently reported that the gold-labeled monoclonal antibody MAb 735, reactive
      with a long-chain form of alpha-2,8-linked polysialic acid (polySia) found on the
      neural cell adhesion molecule (NCAM), is useful to immunohistochemically
      distinguish small-cell lung carcinomas from neuroendocrine carcinomas with higher
      grade of differentiation (carcinoids) and other types of lung carcinomas (Am J
      Pathol 1991;139:297). In this study, we tested the occurrence of polySia in
      various types of malignant thyroid tumors and C-cell hyperplasia to determine
      whether polySia is a useful adjunct for the differential diagnosis of medullary
      thyroid carcinoma (MTC) and other thyroid neoplasms and to distinguish primary
      from secondary (reactive) C-cell hyperplasia (CCH). We examined formaldehyde
      fixed and paraffin-embedded sections of 79 thyroid lesions, consisting of 33 MTC
      (14 familial and 19 sporadic tumors), 13 follicular, 11 papillary, 16 anaplastic
      carcinomas, and four glands with primary and two with secondary CCH. We applied a
      direct and an indirect immunogold-silver technique for polySia, CT, and CEA
      detection, respectively. All 33 MTC showed a strong cell-surface-associated
      immunoreactivity for polySia, which was sensitive to endoneuraminidase digestion.
      The polySia immunoreactivity of nerves served as an internal control in all
      specimens. Immunoreactivity for CT and CEA was present in all MTC with the
      exception of one recurrent tumor with features of an anaplastic MTC type. All
      other thyroid neoplasms were nonreactive for polySia, CT, and CEA. Primary CCH
      associated with MTC showed a strong polySia immunostaining, which was less
      intense in primary CCH not combined with MTC. In normal-appearing C cells and in
      secondary CCH, staining for polySia was absent in the majority of cases. We
      conclude that polySia of NCAM is a valuable marker to distinguish medullary
      carcinomas from other types of thyroid carcinomas. Furthermore, it allows for the
      discrimination of primary from secondary C-cell hyperplasia and may be helpful to
      better define the normal range of C cells in unaffected members of a family with
      a history of multiple endocrine neoplasia (MEN)-II.

PMID- 8141432
TI  - Paraganglia of the prostate. Location, frequency, and differentiation from
      prostatic adenocarcinoma.
AB  - In contrast to paraganglia of the urinary bladder, prostatic paraganglia have
      been largely unreported. Following the discovery of paraganglia in two separate
      radical prostatectomy specimens, we reviewed 100 randomly selected radical
      prostatectomy specimens to document the location and frequency of prostatic
      paraganglia. Twelve additional paraganglia were identified in eight resections,
      for a total of 14 paraganglia in 10 cases. Most paraganglia were located in or
      adjacent to lateral neurovascular bundles and, rarely, in lateral prostatic
      stroma. The size of paraganglia ranged from 0.1 to 1.7 mm (median 0.9 mm).
      Paraganglia consisted of clusters of cells in patterns that ranged from lobular
      to diffuse, usually with a prominent stromal vascular component. The cells
      contained bland oval nuclei and clear cytoplasm, which was often abundant.
      Occasionally, larger cells with larger nuclei were present. Immunohistochemical
      stains for chromogranin, neuron-specific enolase, and synaptophysin were
      positive; those for prostatic-specific antigen were uniformly negative. In one of
      our cases, histologic similarity was noted between a paraganglion and an adjacent
      prostatic adenocarcinoma with a "hypernephroid" pattern. Recognition of prostatic
      paraganglia, with appropriate immunohistochemical stains when necessary, will
      obviate the possibility of confusing these structures with prostatic
      adenocarcinoma.

PMID- 8141433
TI  - Unlikely origin of trabecular hindgut carcinoids from crypt cell proliferative
      micronests.

PMID- 8141434
TI  - Immunodiscrepancy (IMDI)

PMID- 8141435
TI  - [The effect of theophylline on the mucociliary clearance function in ventilated
      intensive care patients].
AB  - Mucociliary clearance represents an important protective mechanism of the upper
      and lower respiratory tracts whereby inhaled particles and micro-organisms are
      removed from the tracheobronchial system. In incubated intensive care unit (ICU)
      patients, impaired ciliary function and mucus transport are associated with
      pulmonary complications [9]. Some authors have shown that theophylline increases
      mucus transport in healthy subjects and patients with chronic bronchitis [8, 16,
      31, 36]. However, other investigators have found unconvincing or conflicting
      results [4, 20, 25]. Therefore, we studied the influence of theophylline on
      bronchial mucus transport velocity (BTV) in ventilated ICU patients. METHODS. The
      study was approved by the ethnics committee of our hospital. In a placebo
      controlled double-blind study, the effect of therapeutic serum concentrations (10
      20 micrograms/ml) of theophylline on BTV in ventilated patients in a surgical ICU
      was investigated. Group 1 (n = 10) served as controls and received placebo. The
      patients of group 2 (n = 10) were given intravenous infusions of 5 mg/kg body
      weight theophylline over 20 min, followed by 1 mg/kg per hour. Before
      administration of theophylline and 1 h after starting the infusion BTV, serum
      theophylline concentrations, and arterial blood gases were measured. Heart rate
      and blood pressure were registered every 5 min. In an additional study, the
      effect of theophylline on BTV at subtherapeutic serum concentrations (5
      micrograms/ml) was investigated. BTV was measured with a small volume (0.05-0.08
      ml) of albumin microspheres labeled with technetium-99m, which was deposited on
      the dorsal surface at the lower ends of the right and left main bronchi via a
      catheter placed in the inner channel of a fibre-optic bronchoscope. The movement
      of the microspheres towards the trachea was visualised and recorded using a
      scintillation camera [10]. RESULTS. The theophylline treatment induced a
      significant improvement in BTV from 3.8 to 7.6 mm/min in the left main bronchus
      and from 0.5 to 5.4 mm/min in the right, while placebo was inactive. The increase
      in BTV, however, was associated with an increase in heart rate; in 3 patients the
      theophylline infusion had to be stopped because of severe tachycardia. Blood
      gases and blood pressures did not change. Theophylline at subtherapeutic
      concentrations had no effect on either BTV or heart rate. CONCLUSIONS.
      Theophylline at therapeutic concentrations improves bronchial mucus transport in
      intubated ICU patients. The increase in BTV may be associated with severe
      tachycardia, and therefore routine application cannot be recommended.

PMID- 8141436
TI  - [Resuscitation skills of hospital nursing staff].
AB  - The hospital nursing staff represents a distinct group of cardiopulmonary
      resuscitation (CPR) providers. Differences in the success rates of resuscitation
      attempts inside or outside the hospital seem to be attributable to the skill of
      the various rescuers. Whereas the definite success rate for prehospital
      resuscitation is 7%, the corresponding rate for in-hospital settings is 15%.
      METHODS. During 53 CPR refresher courses offered to nursing staff members, their
      individual skills and competence in CPR procedures were examined according to the
      standards and guidelines of the German Medical Association (Bundesarztekammer).
      The efficacy of cardiac massage and artificial ventilation performed by each
      nurse was recorded. Quality criteria were defined, grouped and analysed
      statistically by the Chi-square test. RESULTS. Only 6.6% of the nursing staff
      were found to have good skills in artificial ventilation. The main faults
      observed were insufficient tilting of the head (24%) and failure to prevent
      leakage from the insufflation airway (35%). For 42.8% it proved impossible to
      insufflate a minimum ventilatory tidal volume of 400 ml. The attempts at
      resuscitation made by 58.6% were completely inadequate. Although 14.1% of the
      nurses carried out effective cardiac massage, the majority of the test group
      (44.7%) failed to do so. For 29.4% the appropriate position of their own upper
      body to allow adequate chest compression remained elusive. In 41.4% of the
      compression cycles, the rescuer's hands lost contact with the sternum. The
      compression period proved too long in relation to the decompression period in
      21.4%. Only 4 individuals (0.9%) were able to perform all standard CPR procedures
      as recommended by the guidelines and 71.8% failed to perform effective CPR
      manoeuvers. The test results did not differ with respect to the nurses'
      educational or professional status, clinical CPR experience or work area within
      the hospital. CONCLUSION. Cardiopulmonary resuscitation skills of hospital nurses
      are inadequate, mainly because of lack of manual dexterity. Obviously the special
      skills learned in CPR courses are lost after a relatively short time. These
      results, however, do not suggest completely inadequate handling of CPR procedures
      in the hospital setting. Indeed an increasing rate of successful resuscitations
      inside the hospital (up to 27%) has been reported in the literature. In
      consequence of our findings, refresher courses in specific CPR techniques must be
      demanded, which should be made obligatory for nursing staff every 2 years.
      Qualified nursing personnel routinely trained in CPR and supported by effective
      hospital logistics is essential if the life-saving benefits of modern CPR are to
      be provided to our patients.

PMID- 8141437
TI  - [Determination of intrinsic PEEP during mechanical ventilation. Validation of a
      new optional method of measurement provided by the EVITA mechanical ventilator].
AB  - Intrinsic positive end-expiratory pressure (PEEPi) occurring during mechanical
      ventilation depends on expiratory time constants, expiratory volume and
      expiration time as well as on external flow resistance (tubes, valves, etc.). It
      is not routinely determined in mechanically ventilated patients, but it is
      necessary to optimize respirator settings. The aim of the present study was the
      validation of an automated PEEPi determination method implemented in the
      respirator EVITA (Dragerwerke, Lubeck) in mechanically ventilated patients with
      acute lung failure. PATIENTS. The method was validated in ten sedated, myorelaxed
      patients with respiratory insufficiency of different etiologies (five with
      restrictive, and five with obstructive pulmonary disease). PEEPi was determined
      using the volume constant ventilatory mode at ZEEP or at an external PEEP of 5 as
      well as 10 cm H2O. METHOD. PEEPi was first determined with the automated method
      implemented in the EVITA (five measurements at each end-expiratory pressure
      level; PEEPEvita). Steady-state was attained between each measurement. These
      values were compared to the results obtained with end-expiratory occlusion
      (external, computer-controlled valve in the inspiratory limb of the circuit) at
      the respective pressure levels (PEEPEEO). The average of five measurements at
      each PEEP level with each method was defined as PEEPi for the particular
      ventilatory situation. Gas flow was measured at the proximal end of the
      endotracheal tube with a heated pneumotachometer (Fleisch no. 2, Fleisch,
      Lausanne, Switzerland) and a differential pressure transducer. Tracheal pressure
      was determined in the same position with a further differential pressure
      transducer (Dr. Fenyves & Gut, Basel, Switzerland). After A/D conversion, data
      were sampled with a frequency of 20 Hz and processing as well as for control of
      the occlusion valve was self-programmed. For the statistical analysis we used the
      Mann-Whitney U-test or Wilcoxon signed-ranks test; a P value less than 0.05 was
      considered significant. RESULTS. At the given respiratory setting and without
      PEEP patients with obstructive lung disease had a higher PEEPi (median: 6.4 cm
      H2O; range: 5.0-9.6 cm H2O) than those with restrictive pulmonary disease
      (median: 2.3 cm H2O; range: 0.8-3.0 cm H2O) (P < 0.05). Increasing external PEEP
      to 5 or 10 cm H2O significantly decreased the pressure difference between PEEPi
      and external PEEP (P < 0.05), but was unable to eliminate it completely. There
      was no statistically significant difference between PEEPEEO and PEEPEvita (P =
      0.43; Wilcoxon signed-ranks tests). Regression analysis showed a highly
      significant correlation between PEEPEEO and PEEPEvita values (r = 0.985, P <
      0.001; y = 1.03 x-0.18). DISCUSSION. PEEPi occurs during ventilation in patients
      with obstructive and restrictive lung disease. The difference between external
      end-expiratory pressure and PEEPi decreases with increasing external PEEP.
      However, PEEPi may increase with increasing external PEEP in some instances. The
      reason for this may be that the PEEPi determined at the proximal end of the
      endotracheal tube represents only a mean value of different PEEPi values of
      various lung regions. Increasing external PEEP only partially alters this mean
      value due to an effect on PEEPi values lower than external PEEP. The PEEPi values
      measured by the EVITA respirator compared with classical end-expiratory occlusion
      with an external valve were nearly identical. Unfortunately, PEEPi measurement of
      the EVITA can only be performed during controlled and not during assisting (PSV,
      BIPAP etc.) ventilation. Optimal respirator settings require a knowledge of PEEPi
      (i.e., adaption of external PEEP for lowering the work of breathing in COPD
      patients or prolongation of the expiratory phase to avoid unwanted side effects
      of an occult PEEPi on the circulation). Since mo

PMID- 8141438
TI  - [Fulminating E. coli sepsis in Fournier's gangrene].
AB  - Fournier's gangrene is a necrotising soft-tissue infection of the scrotum and
      perineal region caused by gram-negative and gram-positive Enterobacteriaceae. The
      disease is characterised by its unique appearance, its speed of onset, and its
      high mortality. CASE REPORT. A 26-year-old male presented to the emergency room
      complaining of a painful, tremendously swollen scrotum and penis (Fig. 1) that
      had developed within the past 24 h. Later, slurred speech, pallor, and
      hypotension were recognised, leading to the patient's admission to the intensive
      care unit. Suspecting a severe internal haemorrhage, vigorous volume therapy was
      started using crystalloids and colloids until blood and fresh frozen plasma were
      available. One hour later, septic shock was presumed and therapy augmented by IV
      antibiotics, tracheal intubation, and mechanical ventilation. Despite all
      efforts, the patients condition deteriorated rapidly and he died a few hours
      later due to multiple organ failure in septic shock. Postmortem, a perforated
      external hemorrhoidal node was found to be the primary focus of sepsis.
      Microbiologic cultures revealed Escherichia coli in blood and tissue samples.
      DISCUSSION. Fournier's gangrene is a rare disease; nevertheless, its clinical
      picture has to be recognised immediately in order to provide appropriate
      treatment in time. It occurs predominantly in males after minor trauma,
      colorectal or urological disease, and perineal or abdominal surgery. Fournier's
      gangrene usually begins with itching and pain in the scrotal region followed by
      swelling and dark-blueish discolouration of the scrotum and penis, occasionally
      including the lower abdominal wall. Fever and chills are usually present. The
      illness progresses to severe prostation and septic shock with a mortality of 20%
      50%. Tissue cultures mostly reveal E. coli, gram-positive enterococci,
      Pseudomonas, Proteus, and various anaerobes. The treatment should include
      immediate radical surgical debridement, i.v. administration of broad-spectrum
      antibiotics, and cardiopulmonary support. CONCLUSION. The dramatic course of
      Fournier's gangrene requires early recognition, extensive surgical debridement,
      as well as intensive care treatment in order to prevent irreversible septic
      shock.

PMID- 8141439
TI  - [Horner's syndrome following epidural anesthesia].

PMID- 8141440
TI  - [The laryngeal mask as an instrument].
AB  - The laryngeal mask (LM) was developed by A. Brain to overcome the disadvantages
      of the face mask (impractical) and the tracheal tube (invasive). Today this new
      instrument is applied on a broad scale in Great Britain and with growing interest
      in continental Europe. The laryngeal mask comes in five sizes to fit five
      different age groups. The blindly applied technique of positioning the LM can be
      easily learned. Spontaneous or artificial ventilation is possible if the LM is in
      the correct position. Mechanical ventilation may lead to the insufflation of air
      into the stomach. Therefore, ventilatory peak pressure should not exceed 20-25 cm
      H2O and ventilation must be closely monitored. The risk of aspiration can be
      avoided by the proper selection of patients. The LM may be used with different
      anaesthetic techniques; muscle relaxant drugs are not mandatory. The authors have
      applied this mask more than 300 times, and this new instrument obviously has
      potential for different clinical indications. The LM may be applied for short
      surgical interventions in all age groups except premature infants. Complications
      such as regurgitation, aspiration and laryngospasm can be avoided by the
      awareness of the anaesthetist and by an adjusted deep plane of anaesthesia. Apart
      from anaesthesia, the LM can be used for bronchoscopy in children, for difficult
      intubations and as a preliminary airway in cases of resuscitation. Two studies
      performed in Great Britain have evaluated the LM for resuscitation. The
      investigations should be confirmed in German-speaking countries.

PMID- 8141441
TI  - [The prognostic relevance of preoperative pulmonary function tests].
AB  - At Leipzig University, preoperative pulmonary function testing has been performed
      for about 3 years in order to detect and classify patients at high pulmonary
      risk. During the postoperative period, the risk of developing pulmonary
      complications is particularly high due to factors influencing respiratory
      mechanics such as the supine position, pain, residual effects of narcotic drugs,
      etc. It has often been emphasised that an underlying ventilatory disturbance such
      as obstructive lung disease or smoking may enhance the postoperative pulmonary
      risk, although the extent of the influence of preoperative pulmonary diseases on
      the postoperative complication rate is still controversial. The prediction of
      postoperative lung function from preoperative spirometric values is complicated
      by factors such as patient cooperation, pulmonary complications secondary to
      aspiration, infection, peritonitis, etc., and by differing and therefore non
      comparable postoperative care. For this reason, the criteria for assessing
      pulmonary risk vary widely. METHODS. We examined 339 patients (mean age 59.3
      years) preoperatively by quiet and forced spirometry; in most cases we also
      measured airway resistance and functional residual capacity. We estimated the
      postoperative lung function using the quadrant scheme of Miller and compared this
      risk class with our spirometric diagnosis and the postoperative clinical course.
      RESULTS. According to our results, Miller's classification seems inadequately
      differentiated for patients with mild to moderate ventilatory disturbances. A
      relatively high percentage of these patients were considered to have normal
      postoperative lung function. Some patients with severely diminished pulmonary
      function were classified as having sufficient postoperative lung function. The
      number and severity of pulmonary complications also corresponded better with the
      spirometric diagnosis, which was made using all spirometric parameters and not
      only vital capacity (VC) and 1-s forced expiratory volume (FEV1). We found that
      the percentage of primary respiratory complications increased with deterioration
      of the preoperative spirometric values. To provide a prognostic model combining
      both the advantages of using only a few parameters (FEV1, VC) and appropriate
      risk assessment, we propose a modification of the Miller scheme consisting of
      five risk classes. The analysis of the respiratory therapy regimen was
      unsatisfactory because of discrepancies between the predicted pulmonary risk, the
      use of respiratory therapy, and the occurrence of pulmonary complications.
      CONCLUSIONS. For minimising perioperative pulmonary complications, respiratory
      care (prophylaxis and therapy) adequate for the functional risk of the patient is
      necessary. We assume that intensive pre- and postoperative respiratory care and
      therapy in patients with underlying reductions in ventilatory function can help
      to avoid or reduce respiratory complications. The modification of Miller's scheme
      proposed after evaluating the postoperative course of our patients provides a
      differentiated prognostic model that allows the establishment of an appropriate
      and economical therapeutic regimen of perioperative pulmonary care.

PMID- 8141442
TI  - [No inhibition of intestinal motility following ketamine-midazolam anesthesia. A
      comparison of anesthesia with enflurane and fentanyl/midazolam].
AB  - Postoperative intestinal atonia is a complication which is likely to occur in
      patients predisposed for constipation and in patients after intra-abdominal
      operations. The postoperative delay of bowel movement, however, is often also
      related to the type of anaesthesia being used. In order to evaluate the magnitude
      of an anaesthetic-induced postoperative delay of bowel movement, two types of
      intravenous-based anaesthesia using fentanyl/midazolam (1 mg/25 mg; dosage 0.1
      ml/kg/h), and ketamine/midazolam (250 mg/25 mg; dosage 0.1 ml/kg/h) respectively
      were compared with a volatile anaesthetic technique (enflurane; mean
      concentration 1.5 vol%). METHODS. In three groups of patients (each n = 15)
      undergoing elective surgery of the lower extremities, induction of anaesthesia
      was accomplished with methohexital (1-1.5 mg/kg) to facilitate intubation. For
      the maintenance of muscle relaxation vecuronium bromide was used. All patients
      were given droperidol to prevent postoperative emesis, and they were artificially
      ventilated with N2O/O2 (60:40) to normal end-expiratory CO2 concentrations. No
      anticholinergic agents were used at the end of operation since they are known to
      interfere with bowel motility. In order to determine gastro-intestinal motility,
      the H2 exhalation test was used. For this purpose 40 g lactulose in 100 ml of
      water was given to all patients via a gastral tube shortly before extubation.
      Lactulose is broken down by bacteria once it enters the colon, and H2 is
      released, taken up by the vascular system and exhaled. Postoperatively, patients
      were asked to exhale into a 20-ml syringe every 10 min. The content was analysed
      for hydrogen (ppm), using an electrochemical sensor (GMI exhaled hydrogen
      monitor). From the time of lactulose instillation to a threefold increase in end
      expiratory hydrogen concentration (compared to the preoperative value), gastro
      coecal transit time was computed. RESULTS. All three groups of patients were
      comparable in age, height and body weight. Also, the duration of operation was
      comparable in all three groups. Mean gastro-coecal transit time was 204 (+/-
      19.6, SD) min following enflurane, 302 (+/- 32.8 SD) min following fentanyl/
      midazolam and 210 (+/- 28.8 SD) min following ketamine/midazolam anaesthesia. The
      gastro-intestinal inhibition after the opioid-based anaesthetic technique was
      significantly prolonged (p < 0.001, Kruskal-Wallis test). There was no
      significance between patients after ketamine-based anaesthesia and those who had
      the volatile anaesthetic. DISCUSSION AND CONCLUSION. When using intravenous
      anaesthesia with an opioid, gastro-intestinal inhibition, especially in patients
      prone to have constipation, is likely to develop postoperatively. In classical
      neuroleptanaesthesia and in analgosedation in the ICU, the simultaneous use of
      the butyrophenone droperidol seems to counteract the inhibition of opioid-related
      gastrointestinal motility. In cases of opioid-related gastrointestinal atonia a
      gastrokinetic compound may be necessary to overcome this effect on intestinal
      motility.

PMID- 8141443
TI  - [Total i.v. anesthesia with S-(+)-ketamine in orthopedic geriatric surgery.
      Endocrine stress reaction, hemodynamics and recovery].
AB  - Clinically-used ketamine is a racemic mixture of two isomers, S-(+)- and R-(-)
      ketamine. Previous investigations showed the anaesthetic potency of S(+)-ketamine
      to be three times higher than that of R-(-)-ketamine. It was the aim of this
      study to compare the effects of S-(+)-ketamine and racemic ketamine on endocrine
      and cardiovascular parameters, recovery, and side effects in geriatric patients
      during total intravenous anaesthesia (TIVA) for orthopaedic surgery. METHODS:
      Forty patients over 60 years of age scheduled for elective hip or knee
      replacement were investigated in a double-blind, randomised design. For induction
      of TIVA, patients received 0.1 mg midazolam, 0.5 mg atropine, 1 mg/kg S(+)
      ketamine or 2 mg/kg racemic ketamine, respectively, 2 mg vecuronium, and 1.5
      mg/kg suxamethonium. After intubation and relaxation with a total dose of 0.1
      mg/kg vecuronium, a continuous infusion of 2 mg/kg per hour S-(+)- or 4 mg/kg per
      hour racemic ketamine was administered throughout surgery. Blood samples were
      taken through a central venous catheter at seven time-points, before induction as
      well during and after surgery, until the 1st postoperative morning for analysis
      of adrenaline, noradrenaline (by high-pressure liquid chromatography with
      electrochemical detection), anti-diuretic hormone (ADH), adrenocorticotropic
      hormone (ACTH), cortisol (by radioimmunoassay), glucose, and lactate. In
      addition, systolic arterial pressure (SAP), heart rate (HR), and arterial oxygen
      saturation were measured, and the time intervals between the end of ketamine
      infusion and the return of consciousness and orientation were protocolled. The
      incidence and assessment of dreams and other side effects were reported by the
      patients. RESULTS: Biometric data of the groups were comparable, the mean age of
      both groups being 68 years. Plasma adrenaline, noradrenaline, ADH, ACTH,
      cortisol, and glucose as well as SAP and HR increased significantly (P < 0.05)
      during the course of anaesthesia. The influence on lactate levels was not
      significant. There were no differences between S(+)- and racemic ketamine with
      respect to these parameters. Three patients in the ketamine-racemate group showed
      severe arterial hypertension and were withdrawn from the study. Recovery clearly
      improved after administration of S(+)-ketamine compared to the racemate. Simple
      orders were followed after 2.0 +/- 3.4 versus 4.9 +/- 6.8 min (P = 0.07),
      orientation with respect to person returned after 5.7 +/- 4.0 versus 14.6 +/-
      10.0 min (P < 0.001) and spatial orientation after 8.2 +/- 5.4 versus 17.4 +/-
      9.7 min (P < 0.001). After racemic ketamine, 1 patient remembered a negative
      dream and 1 patient a positive dream. In the S(+)-group, 1 positive dream was
      reported. No intraoperative awareness was reported, and all patients would accept
      the same anaesthesia again. CONCLUSIONS: Increases in cardiovascular parameters
      and insufficient reduction of the stress response with respect to ADH, ACTH, and
      cortisol seem to require a more potent hypnotic element during TIVA with
      ketamine. With regard to endocrine and cardiovascular parameters, the
      pharmacodynamic effects of racemic and S-(+)-ketamine were comparable. Because of
      the significant improvement in recovery and the reduced quantitative drug load, S
      (+)-ketamine offers a clinical advantage compared with currently used racemic
      ketamine.

PMID- 8141444
TI  - Unresolved issues relating to peer review, industry support of research, and
      conflict of interest.

PMID- 8141445
TI  - Midlatency auditory evoked potentials and explicit and implicit memory in
      patients undergoing cardiac surgery.
AB  - BACKGROUND: A high incidence of intraoperative awareness during cardiac surgery
      has been reported. Midlatency auditory evoked potentials (MLAEP) have been used
      recently as an indicator of awareness. In the current study, memory for
      information presented during anesthesia was investigated using MLAEP as one
      experimental indicator in 45 patients scheduled for elective cardiac surgery.
      METHODS: In all patients general anesthesia was maintained using high-dosage
      fentanyl (1.2 mg.h-1). In addition, the patients of group 1 (n = 10) received
      flunitrazepam (1.2 mg.h-1), the patients of group 2 (n = 10) isoflurane (0.6-1.2
      vol%), and the patients of group 3 (n = 10) propofol (4-8 mg.kg-1.h-1). Group 4
      (n = 15) served as a control, and those patients were assigned randomly to one of
      the anesthetic regimes. After sternotomy and before cardiopulmonary bypass, an
      audiotape, which included an implicit memory task, was presented to the patients
      of groups 1-3. Auditory evoked potentials were recorded while the patients were
      awake and during general anesthesia immediately before and after the audiotape
      presentation. Latencies of the brain stem peak V and the early cortical
      potentials Na and Pa were measured. RESULTS: Three to 5 days postoperatively no
      patient had a clear explicit memory of intraoperative events. However, there were
      statistically significant differences in the incidence of implicit recall among
      the groups. Five patients in the flunitrazepam-fentanyl group, 1 patient in the
      isoflurane-fentanyl group, 1 patient in the propofol-fentanyl group, and no
      patient in the control group showed an implicit memory of the intraoperative tape
      message. In the awake state, MLAEP showed high peak-to-peak amplitudes and a
      periodic waveform. In the patients with implicit memory postoperatively, MLAEP
      continued to show this pattern during general anesthesia. The early cortical
      potentials Na and Pa did not increase in latency or decrease in amplitude before
      or after the audiotape presentation. In contrast, in the patients without
      implicit memory, MLAEP waveform was severely attenuated or abolished. Na and Pa
      showed marked increases in latencies and decreases in amplitudes or were
      completely suppressed. In 9 patients, including all patients (7 of 9) with
      implicit memory, Pa latency increased less than 12 ms, and 21 of 23 patients
      without implicit memory showed a Pa latency increase of greater than 12 ms during
      anesthesia and the audiotape presentation. Therefore, the Pa latency increase of
      greater or less than 12 ms may provide sensitivity of 100% and specificity of 77%
      in distinguishing patients with implicit memory from patients without implicit
      memory postoperatively. CONCLUSIONS: When the early cortical potentials of MLAEP
      are preserved during general anesthesia, auditory information may be processed
      and remembered postoperatively by an implicit memory task.

PMID- 8141446
TI  - Core hypothermia and skin-surface temperature gradients. Epidural versus general
      anesthesia and the effects of age.
AB  - BACKGROUND: Inadvertent hypothermia occurs frequently during surgery and may be
      associated with adverse outcomes. Although various anesthetic agents have been
      shown to impair thermoregulation, the impairment with regional and general
      anesthetics has not been directly compared. METHODS: Thirty patients undergoing
      radical retropubic prostatectomy were randomly allocated to receive epidural (EA,
      n = 15) or general (GA, n = 15) anesthesia. Tympanic membrane measurements were
      used to assess core temperature. Forearm and calf skin-surface temperature
      gradients were used to assess thermoregulatory vasoconstriction (forearm minus
      fingertip > 4 degrees C and calf minus toe > 6 degrees C). The two groups were
      compared during the intraoperative and early postoperative periods to identify
      differences. Subgroup analysis was used to compare core temperatures and skin
      surface gradients in younger (< 62 yr of age) and older (> or = 62 yr) patients
      in the EA and GA groups. RESULTS: Mean tympanic membrane temperatures were
      similar at all time periods in the EA and GA groups and were nearly identical at
      the end of the surgical procedure (EA, 35.5 +/- 0.2 degrees C; GA, 35.6 +/- 0.2
      degrees C) (P = 0.68). Intraoperatively, the EA group maintained a significant
      forearm skin-surface gradient compared to the GA group (P = 0.0001), whereas the
      calf gradients were minimal and were similar between groups. Postoperatively,
      both groups had comparable positive forearm gradients, whereas calf gradients
      were greater in the GA group (P = 0.001). Mean core temperatures and forearm
      gradients were not different between the younger and older patients receiving GA.
      In those receiving EA, the younger patients had greater mean core temperatures (P
      = 0.015) and greater forearm gradients (P = 0.05) for most of the perioperative
      period. CONCLUSIONS: The EA and GA groups had virtually identical core
      temperature profiles during the intraoperative and post-operative periods.
      Comparison of skin-surface gradients suggests that EA is associated with less
      intraoperative upper-body thermoregulatory impairment but greater and persistent
      post-operative lower-body impairment. During EA, younger patients appeared to
      maintain thermoregulatory activity relative to the older patients. In patients
      receiving GA, the age-related differences were minimal.

PMID- 8141447
TI  - Ventilation-perfusion inequality in patients undergoing cardiac surgery.
AB  - BACKGROUND: Impaired gas exchange is a major complication after cardiac surgery
      with the use of extracorporeal circulation. Blood gas analysis gives little
      information on underlying mechanisms, in particular if the impairment is
      multifactorial. In the current study we used the multiple inert gas technique
      with recordings of hemodynamics to analyze the separate effects of intrapulmonary
      shunt (QS/QT), ventilation-perfusion (VA/Q) mismatch, and low mixed venous oxygen
      tension on arterial oxygenation during cardiac surgery. METHODS: VA/Q
      distribution was studied in nine patients undergoing coronary artery
      revascularization surgery. The obtained data related to VA/Q distribution were
      perfusion of lung regions with VA/Q < 0.005 (QS/QT), perfusion of lung regions
      with 0.005 < VA/Q < 0.1 ("low"-VA/Q regions), ventilation of lung regions with 10
      < VA/Q < 100 ("high"-VA/Q regions), and ventilation of lung regions with VA/Q >
      100 (dead space [VD/VT]). In addition, arterial and mixed venous oxygen and
      carbon dioxide tensions and systemic and pulmonary hemodynamics were analyzed.
      Recordings were made before and after induction of anesthesia, after sternotomy,
      45 min after separation from extracorporeal circulation, 4 h postoperatively
      during mechanical ventilation, and on the 1st postoperative day during
      spontaneous breathing. RESULTS: In the awake state, QS/QT was 4 +/- 4%, and
      perfusion of low-VA/Q regions was 3 +/- 5%. The sum of QS/QT and low-VA/Q units
      correlated with the alveolar-arterial oxygen tension gradient (PA-aO2) (r = 0.63,
      P < 0.05). After induction of anesthesia, QS/QT increased to 10 +/- 9% (P =
      0.069). Sternotomy had little effect on shunt, but QS/QT increased to 22 +/- 8%
      (P < 0.01) after separation from extracorporeal circulation, which was correlated
      with a significantly higher PA-aO2 (r = 0.77, P < 0.05). Postoperatively, gas
      exchange improved rapidly, as assessed by a decrease of PA-aO2 from 341 +/- 77 to
      97 +/- 36 mmHg (P < 0.01) and a reduced QS/QT (5 +/- 4%, P < 0.05). On the 1st
      postoperative day, arterial oxygen tension was significantly lower than
      preanesthesia values (58 +/- 6 vs. 68 +/- 8 mmHg, P < 0.05). QS/QT had increased
      to 11 +/- 6% (P < 0.05), but little perfusion of low-VA/Q units was observed. A
      correlation was found between PA-aO2 and QS/QT (r = 0.82, P < 0.03). CONCLUSIONS:
      QS/QT is a major component of impaired gas exchange before, during, and after
      cardiac surgery. QS/QT increases after induction of general anesthesia, probably
      because of development of atelectasis. After separation from extracorporeal
      circulation, accumulation of extravascular lung water or further collapse of lung
      tissue may aggravate QS/QT. Postoperatively, oxygenation improves, possibly
      because of recruitment of previously nonventilated alveoli or resolution of
      extravascular lung water. During spontaneous breathing, additional mechanisms
      such as altered mechanics of the chest, perfusion of low-VA/Q regions, and
      decreased mixed venous oxygen tension may contribute to impaired gas exchange.

PMID- 8141448
TI  - Characterization of prothrombin activation during cardiac surgery by hemostatic
      molecular markers.
AB  - BACKGROUND: Prothrombin activation represents the key regulatory step in the
      hemostatic process. Once formed, thrombin contributes to the generation of fibrin
      as well as the activation of platelets and fibrinolysis. Failure to suppress
      thrombin formation during cardiac surgery could result in disorders of hemostasis
      and thrombosis in the perioperative period. The aim of this study was to
      determine the time course for prothrombin activation during the perioperative
      period associated with cardiac surgery. METHODS: We measured prothrombin
      activation during the perioperative period in 19 adult patients undergoing
      primary cardiac surgery using enzyme-linked immunosorbent assays for the
      detection of thrombin formation (prothrombin fragment 1.2 and thrombin
      antithrombin III complex) and thrombin activity (fibrinopeptide A and fibrin
      monomer). Blood samples were obtained preoperatively; at 30-min intervals during
      cardiopulmonary bypass (CPB); and 1, 3, and 20 h after completion of CPB.
      RESULTS: Despite anticoagulation with heparin, plasma concentrations of
      prothrombin fragment 1.2, thrombin-antithrombin III complex, and fibrin monomer
      increased throughout CPB. Peak concentrations for all hemostatic markers occurred
      in the samples obtained 3 h after completion of CPB. By the morning after
      surgery, plasma prothrombin fragment 1.2 returned to preoperative concentrations;
      however, fibrinopeptide A and fibrin monomer concentrations remained
      significantly increased (P < 0.05) compared to preoperative values. CONCLUSIONS:
      These data clearly demonstrate the occurrence of prothrombin activation and
      thrombin activity during CPB despite heparin concentrations adequate to maintain
      the activated clotting time greater than 400 s. Hemostatic markers for the
      activation of prothrombin demonstrated peak concentrations 3 h after completion
      of CPB with a return to baseline concentrations by the morning after surgery.
      Markers for thrombin activity, however, suggest the presence of active thrombin
      through the morning after surgery. Further investigations will be necessary to
      determine the role of hemostatic activation in thrombotic complications after
      cardiac surgery.

PMID- 8141449
TI  - Monitor surveillance and vigilance of anesthesia residents.
AB  - BACKGROUND: Anesthesia residents take longer to detect changes in electronically
      monitored data during the induction phase of anesthesia during the maintenance
      phase. This study was performed to investigate the reasons for this delay and to
      validate a method of measuring vigilance. METHODS: The activity of ten residents
      was studied during 73 surgical procedures. Data were collected during three 15
      min periods from each case: induction, starting with application of the
      electrocardiograph; maintenance, an arbitrary period between induction and
      emergence; and emergence, ending with detachment of the electrocardiograph.
      Vigilance was measured as the time taken to detect a change, from normal to
      abnormal, of an artificial parameter displayed on the physiologic monitor
      (response time). An observer simultaneously recorded each time that the resident
      looked toward the monitors. RESULTS: Vigilance to the monitor display was less
      during induction and emergence than during maintenance (P < 0.005). Residents
      spent less total time watching monitors during induction than during maintenance
      (P < 0.005), and the duration of each monitor observation was shorter (P <
      0.0005). Anesthesia residents usually looked at the monitors several times before
      detecting the abnormal value. The measure of anesthesia vigilance correlated with
      independent measures of monitor watching time and frequency. CONCLUSIONS: The
      results suggest that during induction of anesthesia, which is a period of high
      anesthesiologist workload, residents glance toward monitors to gather data rather
      than scan displays. The results help to validate the method for measuring
      anesthesia vigilance.

PMID- 8141450
TI  - Sympathetic muscle nerve activity, peripheral blood flows, and baroreceptor
      reflexes in humans during propofol anesthesia and surgery.
AB  - BACKGROUND: With percutaneous recordings of muscle nerve sympathetic activity
      (MSA), it is possible to study interactions between the autonomic nervous system
      and anesthetics. This study describes the effects of propofol infusion both
      before and during microlaryngoscopy. METHODS: Nine patients participated. MSA was
      recorded, muscle and skin blood flows were measured. Sodium nitroprusside-induced
      decreases in blood pressure were used to quantitate baroreceptor reflex
      sensitivity. RESULTS: During steady state propofol anesthesia (0.1 mg.kg-1.min
      1), "total MSA" (MSA burst area per minute) was 37% (P < 0.05) of awake control
      value; leg blood flow recorded by strain-gauge plethysmography was 227%
      (difference not significant); and skin blood flow recorded by laser Doppler
      flowmetry and finger pulse plethysmography was 300% (P < 0.05) and 376% (P <
      0.05) of respective awake control values. During microlaryngoscopy, when mean
      arterial blood pressure was controlled as close as possible to mean arterial
      blood pressure in the awake state by individually adjusted propofol infusion
      rates (average 0.33 mg.kg-1.min-1) MSA was restored to 93% of the activity before
      anesthesia, and leg blood flow increased further. Both cardiac and muscle
      sympathetic baroreflex sensitivities were depressed by propofol. During surgery
      the cardiac baroreflex sensitivity decreased further, whereas the muscle
      sympathetic baroreflex sensitivity was unchanged. CONCLUSIONS: Propofol is a
      potent inhibitor of sympathetic neuronal activity and decreases the sensitivity
      of the baroreflex. When used to control the pressor response during surgery, the
      vasodilatating effect of propofol overrides the neural vasoconstriction induced
      by surgery, and a further inhibition of the cardiac baroreflex is observed.

PMID- 8141451
TI  - The laryngeal mask airway and positive-pressure ventilation.
AB  - BACKGROUND: The utility of the laryngeal mask airway during positive-pressure
      ventilation has yet to be determined. Our study was designed to assess whether
      significant leaks occurred with positive-pressure ventilation and if leaks were
      associated with gastroesophageal insufflation. METHODS: Forty-eight patients
      undergoing elective surgery were studied. After induction of anesthesia and
      paralysis, controlled ventilation was used with four different peak pressure
      settings in each patient (15, 20, 25, and 30 cmH2O). The order of ventilator
      pressure settings was assigned from a randomized block schedule. Data collected
      included inspiratory and expiratory volumes, qualitative assessments of
      gastroesophageal insufflation, and leak at the neck. After data collection during
      laryngeal mask use, the anesthesiologist intubated the trachea and measurements
      were repeated for tracheal tube ventilation. Leak was calculated by subtracting
      the expiratory from the inspiratory volume and expressed as a fraction of the
      inspiratory volume. RESULTS: Ventilation with the laryngeal mask airway was
      adequate at all ventilation pressures and comparable with tracheal tube
      ventilation. Leak fraction (mean +/- SD) at 15, 20, 25, and 30 cmH2O for
      laryngeal mask ventilation were 0.13 +/- 0.15, 0.21 +/- 0.18, 0.25 +/- 0.16 and
      0.27 +/- 0.17, respectively, and 0.03 +/- 0.03, 0.05 +/- 0.03, 0.05 +/- 0.03 and
      0.04 +/- 0.03, respectively, for tracheal tube ventilation. Leak fractions for
      ventilation with the laryngeal mask were consistently greater than those measured
      for tracheal tube ventilation at similar ventilation pressures. Leak fraction
      with laryngeal mask ventilation increased with increasing airway pressures,
      whereas leak with tracheal tube ventilation remained unchanged. The frequency of
      gastroesophageal insufflation ranged from 2.1% at a ventilation pressure of 15
      cmH2O to 35.4% at 30 cmH2O. CONCLUSIONS: Ventilation using the laryngeal mask
      appears to be adequate if airway resistance and pulmonary compliance are normal.
      Gastroesophageal insufflation of air will become a problem in the presence
      increased ventilation pressure.

PMID- 8141452
TI  - Toxicity of compound A in rats. Effect of a 3-hour administration.
AB  - BACKGROUND: Soda lime converts sevoflurane to CF2 = C(CF3)OCH2F, an olefin called
      compound A, whose toxicity raises concerns regarding the safe administration of
      sevoflurane via rebreathing circuits. The present report extends the findings of
      a previous investigation by others of the toxicity of this olefin, and
      establishes concentration-response relationships for such toxicity. METHODS:
      Eighteen groups of ten Wistar rats breathed 0, 25, 50, 100, 200, 300, 350, and
      400 ppm of the olefin in oxygen for 3 h. The olefin concentrations were developed
      in a square-wave manner by injection of saturated vapor followed by a continuous
      delivery of dilute vapor. The lethal concentration in 50% (LC50) of animals was
      estimated by logistic regression. Rats were killed on day 1 or day 4 after
      breathing the olefin, and specimens of brain, kidney, lung, liver, and small
      intestine were obtained from all rats for examination using light microscopy.
      RESULTS: The LC50 equaled 331 ppm (95% confidence limits +/- 13 ppm). No injury
      resulted to lung or small intestine in either the experimental or the control
      group (those breathing only oxygen for 3 h). Renal injury (necrosis of the outer
      strip of the outer medulla, defined in this report as corticomedullary tubular
      necrosis) occurred at 50 ppm and greater; hepatic injury at 350 ppm and greater;
      and cerebral injury only at 400 ppm. CONCLUSIONS: The lethal concentration and
      the threshold for toxicity of the olefin are less than previously reported. The
      threshold for nephrotoxicity reaches the range of values for the olefin that have
      been attained in clinical practice. Further studies are required to determine
      whether these results in rats can be extrapolated to patients.

PMID- 8141453
TI  - Regional vasodilating properties of isoflurane in normal swine myocardium.
AB  - BACKGROUND: Studies of the coronary vasodilating properties of isoflurane have
      produced inconsistent results. Isoflurane has been reported to cause minimal or
      no coronary vasodilation, mild dose-related vasodilation, or even near-maximal
      coronary vasodilation. The current study was performed to clarify the direct
      coronary vasodilating potency of isoflurane. METHODS: We determined the
      vasodilating properties of isoflurane in regionally perfused swine myocardium.
      Six domestic swine were anesthetized with pentobarbital and fentanyl. The left
      anterior descending artery (LAD) was cannulated and perfused with blood drawn
      from the carotid artery and passed thorough a membrane oxygenator. LAD arterial
      flow was controlled by a calibrated roller pump with continuous digital readout,
      and LAD arterial pressure was measured directly. The anterior interventricular
      vein was cannulated and dimension crystals placed in the LAD-perfused myocardium.
      The vasodilation response to 0, 1, 2, and 3% isoflurane administered via the
      membrane oxygenator was determined and compared to maximal vasodilation produced
      by regional intracoronary administration of adenosine. RESULTS: Systemic blood
      pressure and heart rate remained constant throughout the experiment. With 3%
      isoflurane, systolic shortening and regional myocardial oxygen consumption
      decreased by 60 and 20%, respectively. The same concentration increased coronary
      blood flow by 51 +/- 34% and reduced coronary vascular resistance by 32.9 +/-
      11.0%. Neither coronary blood flow nor coronary vascular resistance was affected
      with 1% isoflurane. Regional coronary administration of adenosine produced much
      greater changes in both coronary blood flow (+591%) and coronary vascular
      resistance (-92.5%). Isoflurane increased the venous oxygen content of the
      anterior interventricular vein in a dose-dependent fashion from 4.85 vol% at
      control to 6.17, 7.01, and 8.63 vol% at 1, 2, and 3% isoflurane, respectively.
      CONCLUSIONS: We conclude that isoflurane is a mild dose-dependent coronary
      vasodilator. At a 1% concentration, the coronary vasodilating properties of
      isoflurane are minimal.

PMID- 8141454
TI  - Speed and sensitivity of mechanical versus electrographic indicators to mild or
      moderate myocardial ischemia in the pig.
AB  - BACKGROUND: Intraoperative myocardial ischemia may be detected and quantified by
      indexes of myocardial contraction or by electrography. The relative reliability
      of these two approaches is controversial. Two issues are relevant: the timing of
      events after the onset of mild to moderate ischemia, and the sensitivity of
      measures to ischemia at steady state. METHODS: In eight pigs, a carotid-to-left
      anterior descending coronary artery shunt with a flow meter was installed. Flow
      to the left anterior descending coronary artery was reduced in steps of 10% from
      baseline values to 50% of baseline. Wall thickness, myocardial QRS amplitude, and
      ST-segment deviation were measured every 1 min for 6 min at each step. Regional
      myocardial lactate extraction was measured at 6 min. RESULTS: Linear relations
      were found between the percentage of baseline coronary flow and all four
      dependent variables at steady state, indicating equal sensitivity (defined as
      rate of change with respect to flow reduction) to myocardial ischemia. After flow
      reduction, decreases in systolic wall thickening occurred first and were followed
      by a QRS amplitude decrease and then ST-segment elevation. The onset of ischemia
      was earlier with more severe reductions of coronary flow. CONCLUSIONS: Mechanical
      and electric measures of myocardial ischemia show equal sensitivity at steady
      state even though regional contraction changed more quickly than did QRS
      amplitude or the ST-segment after an abrupt reduction in coronary flow.

PMID- 8141455
TI  - Anesthetic potency is not altered after hypothermic spinal cord transection in
      rats.
AB  - BACKGROUND: In essence, the clinical goal of general anesthesia is to produce a
      state of unresponsiveness and amnesia. These endpoints are commonly achieved with
      drugs like isoflurane, but the sites and mechanisms by which these specific
      endpoints are achieved remain unknown. Blocking the somatic motor response to
      painful stimuli is widely used as an indicator of anesthetic adequacy, and the
      concentration of anesthetic agent (minimum alveolar concentration [MAC]) required
      to achieve this unresponsiveness is the benchmark of anesthetic potency. Recent
      work has demonstrated that precollicular decerebration does not alter MAC in
      rats, suggesting that the forebrain is not a major site of action of isoflurane
      in blocking motor responses. The brain stem contains systems that modulate pain
      processing in the spinal cord. The current study was undertaken to assess the
      relative roles of the brain stem and spinal cord as sites of anesthetic action in
      blocking somatic responsiveness. METHODS: In seven rats, anesthesia was induced
      and maintained with isoflurane in oxygen. MAC was determined by observing the
      response to tail clamp and fore- and hind limb toe pinch at three times: after
      intubation, after cervical laminectomy, and after staged hypothermic spinal cord
      transection. RESULTS: MAC determined by tail clamp did not change during the
      protocol (1.28 +/- 0.08% [mean +/- standard deviation] baseline vs. 1.25 +/-
      0.18% postlaminectomy vs. 1.03 +/- 0.40% posttransection). In one animal, the MAC
      value decreased from a prelesion value of 1.2% to 0.25%, accounting for most of
      the variance in the postlesion mean; the MAC value as determined by withdrawal to
      rear paw pinch was unchanged from its prelesion value in this animal. The MAC
      values as determined by toe pinch in all animals remained unchanged after spinal
      transection of the lesion both rostrally and caudally. CONCLUSIONS: Somatic motor
      responsiveness and its sensitivity to isoflurane appeared to be unaltered despite
      acute loss of descending cortical and bulbar controls. This observation suggests
      that the site of anesthetic inhibition of motor response may be in the spinal
      cord.

PMID- 8141456
TI  - Pulmonary artery occlusion and lung collapse depletes rabbit lung adenosine
      triphosphate.
AB  - BACKGROUND: Although the bronchial circulation has traditionally been thought to
      provide adequate blood flow for the lung when the pulmonary artery is obstructed,
      recent studies have demonstrated that pulmonary artery occlusion results in lung
      injury. We hypothesized that after pulmonary artery occlusion, aerobic lung
      metabolic function is altered. We studied the changes in the concentration of
      adenine nucleotides as markers of injury in the intact rabbit lung after
      pulmonary artery occlusion in the presence and absence of pneumothorax. METHODS:
      A thoracotomy was performed on the rabbits, and on occlusive microvascular clamp
      was placed on the left pulmonary artery. The rabbit lungs were studied after 24 h
      of in vivo left pulmonary artery occlusion (n = 5), 24 h of left pulmonary artery
      occlusion with the lung collapsed by pneumothorax (n = 6), or 24 h of lung
      collapse alone (n = 5). RESULTS: Adenosine triphosphate concentrations of the
      occluded left lung decreased dramatically at 24 h in the group with pulmonary
      artery occlusion and collapse (adenosine triphosphate concentration 196 +/- 32
      ng/g for the left lung and 1,479 +/- 197 ng/g for the right lung; P < 0.001).
      There were no differences between the lungs in the rabbits undergoing occlusion
      alone or collapse alone. CONCLUSIONS: After pulmonary artery occlusion or lung
      collapse, adenine nucleotides are preserved if ventilation is continued. The
      increased permeability of rabbit lungs after 24 h of left pulmonary artery
      occlusion alone cannot be explained on the basis of depletion of high-energy
      phosphates. In the absence of ventilation due to lung collapse, pulmonary artery
      occlusion results in decreased adenosine triphosphate concentrations,
      demonstrating that the residual circulations (bronchial and pulmonary venous
      flow) are inadequate to support normal lung aerobic metabolism.

PMID- 8141457
TI  - Volatile anesthetics inhibit dihydropyridine binding to malignant hyperthermia
      susceptible and normal pig skeletal muscle membranes.
AB  - BACKGROUND: Surface membrane dihydropyridine receptor Ca2+ channels may play a
      role in the response of malignant hyperthermia-susceptible skeletal muscle to
      volatile anesthetics. METHODS: We determined the effect of halothane, enflurane,
      and isoflurane on the binding of the Ca2+ channel blocker PN200-110 to skeletal
      muscle membranes isolated from malignant hyperthermia-susceptible and normal
      pigs. RESULTS: In the presence of 0.4 mM halothane, the maximal [3H]PN200-110
      binding to both normal and malignant hyperthermia membranes was reduced by 37-43%
      (P < 0.05). There was no difference in the equilibrium constant for the halothane
      dependent inhibition of [3H]PN200-110 binding to these two types of membranes.
      There also was no significant difference among halothane, enflurane, or
      isoflurane in their ability to inhibit [3H]PN200-110 binding to either normal or
      malignant hyperthermia membranes. CONCLUSIONS: Volatile anesthetics inhibit the
      binding of PN200-110 to skeletal muscle membranes by decreasing the number of
      functionally active dihydropyridine receptor proteins. This inhibition is similar
      for membranes isolated from both normal and malignant hyperthermia-susceptible
      muscle, thus providing no evidence for a halothane-induced functional defect in
      this protein in malignant hyperthermia-susceptible muscle. However, the results
      of this study also indicate that the mechanism by which volatile anesthetics
      decrease surface membrane Ca2+ currents in skeletal muscle is by reducing the
      number of functional dihydropyridine receptor Ca2+ channels.

PMID- 8141458
TI  - Halothane and isoflurane decrease calcium sensitivity and maximal force in human
      skinned cardiac fibers.
AB  - BACKGROUND: Reports of the direct effects of volatile anesthetics on cardiac
      myofibrils, studied in various mammalian species but not in humans, have
      conflicted. To determine whether volatile anesthetics directly affect cardiac
      contractile proteins in humans, we examined the effects of various equianesthetic
      doses of halothane (0.46, 0.83, and 1.23 mM, equivalent to 0.75, 1.50, and 2.25%,
      respectively) and isoflurane (0.63, 1.22, and 1.93 mM, equivalent to 1.15, 2.30,
      and 3.50%, respectively) on the Ca2+ sensitivity and maximal force in human
      skinned cardiac fibers. METHODS: Left ventricular muscle strips were obtained
      from seven patients undergoing cardiac surgery. Sarcolemma was disrupted with
      EGTA (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid), and
      sarcoplasmic reticulum was destroyed with EGTA plus BRIJ 58 detergent. Ca2+
      sensitivity was studied by observing the isometric tension developed by skinned
      fiber bundles challenged with solutions of increasing Ca2+ concentrations
      expressed in pCa (where pCa = -log10[Ca2+]). Maximal force was measured with a
      pCa 4.8 solution. RESULTS: Both anesthetics shifted the pCa-tension curves toward
      higher Ca2+ concentrations and decreased pCa for half-maximal activation in a
      dose-dependent and reversible fashion (from 5.71 for control to 5.56 and 5.55 for
      1 MAC halothane and isoflurane, respectively) without changing the slope of this
      relationship (Hill coefficient). No differences between agents were observed at
      equianesthetic concentrations. The two agents also decreased the maximal
      activated tension in a dose-dependent fashion (-27 and -28% vs. control for 2 MAC
      halothane and isoflurane, respectively). CONCLUSIONS: The current study indicates
      that halothane and isoflurane decrease Ca2+ sensitivity and maximal force in
      human skinned cardiac fibers at 20 degrees C. If these effects extend to higher
      temperatures, they may contribute to the negative inotropic effect of these
      agents.

PMID- 8141459
TI  - Effects of propofol and thiopental on coronary blood flow and myocardial
      performance in an isolated rabbit heart.
AB  - BACKGROUND: Some clinical and experimental studies suggest that propofol
      decreases myocardial contractility and relaxation, whereas others report
      preserved cardiac function. To investigate the effects of propofol on intrinsic
      contractility and relaxation, increasing concentrations of propofol were infused
      in isolated blood-perfused rabbit hearts. Equimolar concentrations of thiopental
      were infused as a reference group. METHODS: Coronary blood flow, left ventricular
      contractility and relaxation (as maximal positive and negative left ventricular
      pressure derivatives [dP/dtmax and dP/dtmin], respectively), and myocardial
      oxygen consumption (MvO2) were measured during infusion of 10-1,000 microM
      propofol in blood-perfused hearts. To determine whether the effects of propofol
      depend on the heart's perfusate, propofol also was infused in isolated buffer
      perfused rabbit hearts. In addition, the effects of propofol solvent were
      investigated in blood- and buffer-perfused preparations. RESULTS: In blood
      perfused preparations, coronary blood flow increased with propofol concentrations
      greater than 30 microM and with 300 and 1,000 microM thiopental. Left ventricular
      dP/dtmax and dP/dtmin remained unchanged with propofol and decreased with
      concentrations of thiopental equal to or greater than 30 microM. MvO2 increased
      with 1,000 microM propofol, whereas coronary venous oxygen tension and content
      remained unchanged. MvO2 decreased with thiopental associated with a significant
      increase in coronary venous oxygen tension and content. In six buffer-perfused
      hearts, basal coronary blood flow was much greater and MvO2 less than in blood
      perfused hearts. Left ventricular dP/dtmax and dP/dtmin decreased with 30, 100,
      and 300 microM propofol. Propofol vehicle did not change coronary blood flow,
      myocardial performance, or MvO2 of blood- or buffer-perfused hearts. CONCLUSIONS:
      When compared to a reference drug such as thiopental, propofol did not depress
      the myocardial performance of blood-perfused rabbit hearts. The type of the
      perfusate (blood vs. buffer), however, had a major influence on the myocardial
      effects of propofol.

PMID- 8141460
TI  - James Moore (1762-1860). An 18th-century advocate of mitigation of pain during
      surgery.

PMID- 8141461
TI  - Criteria for defining clinical competence of anesthesiology residents. The
      Clinical Competence Committee to the American Board of Anesthesiology.

PMID- 8141462
TI  - Assay methods for sufentanil in plasma. Radioimmunoassay versus gas
      chromatography-mass spectrometry.
AB  - BACKGROUND: The terminal pharmacokinetic parameters of sufentanil have, until
      now, been poorly characterized. This is probably because of the poor sensitivity
      or unreliability of the assay methods used. Radioimmunoassay (RIA) can be a very
      helpful assay method for sufentanil. However, before application to key
      pharmacokinetic studies, it requires adequate validation, e.g., by comparison
      with a method of proven sensitivity and specificity, such as gas chromatography
      mass spectrometry (GC-MS). METHODS: Spiked control plasma samples and 135 plasma
      samples obtained from five patients receiving intravenous doses of 500 or 750
      micrograms sufentanil, as a 10-20-min infusion, were analyzed by an improved,
      sensitive RIA and capillary GC-MS. RESULTS: Both techniques had comparable limits
      of quantitation (0.02 ng/ml). Between-day coefficients of variation in the 0.05
      10-ng/ml concentration range were 8.5-10.5% for the RIA and less than 10% for the
      GC-MS method. The patient plasma concentrations determined by RIA (y) and GC-MS
      (x) showed a good agreement (y = 1.016x + 0.002) and a correlation coefficient of
      0.97. CONCLUSIONS: The results demonstrate the validity of the improved RIA
      method for the determination of sufentanil plasma concentrations.

PMID- 8141463
TI  - Comparison of forced-air patient warming systems for perioperative use.
AB  - BACKGROUND: Perianesthetic hypothermia is common and produces several
      complications, including postoperative shivering, decreased drug metabolism and
      clearance, and impaired wound healing. Forced-air warming transfers more than 50
      W to the body and is an efficient method for either preventing or reversing
      decreases in core temperature. METHODS: The authors compared the efficacy of four
      complete forced-air warming systems: (1) Bair Hugger 250/PACU Patient Warming
      System with 300 Warming Cover (Augustine Medical, Eden Prairie, MN); (2)
      Thermacare TC1000 Power Unit with TC1050 Comfort Quilt (Gaymar Industries,
      Orchard Park, NY); (3) WarmAir 130 Hypothermia System with 140 Warming Tube
      (Cincinnati Sub-Zero Products, Cincinnati, OH); and (4) WarmTouch 5000 Patient
      Warming System and 503-0810 CareQuilt (with the connecting hose compressed
      [short] and extended [long]) (Mallinckrodt Medical, St. Louis, MO). Six minimally
      clothed male volunteers were studied supine in a 24.5 degrees C environment.
      Cutaneous heat flux and skin temperature was measured at 14 area-weighted sites
      using thermal flux transducers. After 20-min control periods, volunteers were
      warmed for 40 min in each condition. A cotton blanket was placed over each cover.
      Power units were placed at the foot end of the bed, started cold, and set at
      maximum temperature and flow settings. All units reached maximum efficiency
      within 20 min. RESULTS: Total heat transfer with the Bair Hugger system (95 +/- 7
      W) was greater (P < 0.05) than with WarmTouch (short hose 81 +/- 6 W and long
      hose 68 +/- 8 W), Thermacare (61 +/- 5 W), and WarmAir (38 +/- 6 W) systems. Each
      cover also was tested on a common power unit (Bair Hugger 200). Total heat
      transfer was greater (P < 0.05) with the Warming Cover (Bair Hugger) (88 +/- 8
      W), followed by the Comfort Quilt (Thermacare) (56 +/- 6 W), CareQuilt
      (WarmTouch) (50 +/- 7 W), and the Warming Tube (WarmAir) (43 +/- 6 W).
      CONCLUSIONS: The advantages of the Bair Hugger system and Warming Cover are
      evident in areas that are important for heat transfer from the periphery to the
      body core (chest, axilla, abdomen, and upper legs).

PMID- 8141464
TI  - Detection of urinary bladder perforation during laparoscopy by distension of the
      collection bag with carbon dioxide.

PMID- 8141465
TI  - Bupivacaine-induced cardiac toxicity in neonates: successful treatment with
      intravenous phenytoin.

PMID- 8141466
TI  - Normal activated clotting time despite adequate anticoagulation with ancrod in a
      patient with heparin-associated thrombocytopenia and thrombosis undergoing
      cardiopulmonary bypass.

PMID- 8141467
TI  - Lung collapse after induction of anesthesia in a healthy outpatient.

PMID- 8141468
TI  - Administration of protamine rather than heparin in a patient undergoing
      normothermic cardiopulmonary bypass.

PMID- 8141469
TI  - Autonomic imbalance of the heart during total spinal anesthesia evaluated by
      spectral analysis of heart rate variability.

PMID- 8141470
TI  - Cricoid pressure for preventing gastric insufflation in infants and children.

PMID- 8141471
TI  - Does the potency of fentanyl vary with different inhalational agents?

PMID- 8141472
TI  - Intravenous fluid preload in the prevention of spinal block-induced hypotension
      in parturients.

PMID- 8141473
TI  - Substance abuse among anesthesiologists.

PMID- 8141474
TI  - Treatment of myofascial pain with botulinum A toxin.

PMID- 8141475
TI  - The laryngeal mask airway: its uses in anesthesiology.

PMID- 8141476
TI  - Should malignant hyperthermia-susceptible patients undergo muscle biopsy?

PMID- 8141477
TI  - Subarachnoid catheters and the cauda equina syndrome: hypotheses in need of
      trial.

PMID- 8141478
TI  - Severe sepsis after intravenous injection of contaminated propofol.

PMID- 8141479
TI  - A simple alternative method for nasogastric tube suction connections.

PMID- 8141480
TI  - Plateletpheresis before cardiopulmonary bypass.

PMID- 8141481
TI  - Plateletpheresis before cardiopulmonary bypass.

PMID- 8141482
TI  - Pacemaker interactions with transcutaneous cardiac pacing.

PMID- 8141483
TI  - Effect of cryoprecipitate and plasma on plasma von Willebrand factor multimeters
      and bleeding time in Doberman Pinschers with type-I von Willebrand's disease.
AB  - We determined whether administration of cryoprecipitate or fresh-frozen plasma
      (FFP) would enhance glass bead platelet retention and shorten the bleeding time
      in von Willebrand factor (vWf)-deficient Doberman Pinschers. Plasma concentration
      of vWf was < 15% of the reference value in these dogs and, on the basis of
      multimeric analysis of vWf, these dogs had type-I von Willebrand's disease (vWd).
      Concentration of vWf in cryoprecipitate (prepared from FFP of clinically normal
      dogs) was enriched almost 20 times, and the preparation was a concentrate of the
      largest and most physiologically active multimers. Administration of a dose of
      cryoprecipitate calculated to increase plasma vWf concentration of recipient dogs
      to 50 U/dl increased plasma vWf concentration in recipient dogs to about 40 U/dl.
      Mean buccal mucosal bleeding time (BMBT) shortened from 6.7 minutes before
      treatment to 3.8 minutes at 2 hours after treatment. Cryoprecipitate from donor
      dogs treated with deamino-8-D-arginine vasopressin (1 micrograms/kg of body
      weight) effectively shortened mean BMBT from 6.4 minutes to 3.1 minutes.
      Administration of cryoprecipitate from vWf-deficient dogs prolonged, rather than
      shortened, the BMBT. After FFP (450 ml) infusion, plasma vWf concentration
      increased in recipient dogs, but the BMBT did not shorten. Glass bead platelet
      retention did not change after administration of cryoprecipitate or FFP.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141484
TI  - Cardiopulmonary effects of halothane in hypovolemic dogs.
AB  - Cardiopulmonary effects of halothane administration were studied in hypovolemic
      dogs. Baseline cardiopulmonary data were recorded from conscious dogs after
      instrumentation. Hypovolemia was induced by withdrawal of blood from dogs until
      mean arterial pressure of 60 mm of Hg was achieved. Blood pressure was maintained
      at 60 mm of Hg for 1 hour, by further removal or replacement of blood. Halothane
      was delivered by face mask, dogs were intubated, then halothane end-tidal
      concentration of 1.13 +/- 0.02% was maintained, and cardiopulmonary effects were
      measured 3, 15, 30, and 60 minutes later. After blood withdrawal and prior to
      halothane administration, systemic vascular resistance index, oxygen extraction,
      and base deficit increased. Compared with baseline values, these variables were
      decreased: mean arterial pressure, mean pulmonary arterial pressure, pulmonary
      arterial occlusion pressure, cardiac index, oxygen delivery index, oxygen
      consumption index, mixed venous oxygen tension, mixed venous oxygen content,
      venous admixture, arterial bicarbonate concentration, and mixed venous pH. At all
      times after intubation, arterial and venous oxygen tensions and mixed venous
      carbon dioxide tensions were increased. Three minutes after intubation, base
      deficit and mixed venous carbon dioxide tension increased, and mean arterial
      pressure and arterial and venous pH decreased, compared with values measured
      immediately prior to halothane administration. Fifteen minutes after intubation,
      systemic vascular resistance index decreased and, at 15 and 30 minutes, mean
      arterial pressure and arterial and venous pH remained decreased. At 60 minutes,
      mean pulmonary arterial pressure and pulmonary arterial occlusion pressure were
      increased and mixed venous pH was decreased, compared with values measured before
      halothane administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141485
TI  - Comparison of two ultralente insulin preparations with protamine zinc insulin in
      clinically normal cats.
AB  - The absorption kinetics and glycemic effects of 3 long-acting insulin
      preparations (protamine zinc beef-pork insulin, ultralente beef-pork insulin, and
      ultralente human insulin) were evaluated in 9 healthy, adult, domestic shorthair
      cats (6 males, 3 females). A triple crossover study was performed, in which the
      serial serum concentrations of insulin and glucose were determined over a 24-hour
      period after SC administration of the 3 insulin preparations (dosage, 1.0 U/kg of
      body weight) at 3-week intervals. A control study was also performed in 4 of the
      cats by serially collecting samples for insulin and glucose determinations after
      administration of insulin diluent. After administration of protamine zinc insulin
      (PZI), mean (+/- SEM) serum insulin concentration increased significantly (P <
      0.05) above baseline, reached a peak value (484 +/- 287 pmol/L) at 1 hour, and
      remained significantly (P < 0.05) higher than baseline at 24 hours. After
      administration of ultralente human insulin, the serum insulin curve was similar
      to that obtained after PZI administration, but mean serum insulin concentration
      took longer to peak (538 +/- 177 pmol/L at 4 hours). After administration of
      ultralente beef-pork insulin, mean peak serum insulin concentration was lower
      (220 +/- 54 pmol/L, not statistically significant) than that obtained after
      administration of PZI and ultralente human insulins; it then decreased to values
      statistically indistinguishable from baseline by 16 hours. The area under the
      serum insulin concentration curve for PZI (5,063 +/- 681 pmol x h/L) and
      ultralente human insulin (4,138 +/- 439 pmol x h/L) was significantly (P < 0.05)
      larger than that for ultralente beef-pork insulin (2,378 +/- 561 pmol x
      h/L).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141486
TI  - Effect of interleukin 1 on articular cartilage from young and aged horses and
      comparison with metabolism of osteoarthritic cartilage.
AB  - The effect of interleukin 1 (IL-1) on equine articular cartilage was
      investigated, using a cartilage explant culture system. Measurement of [35S]O4
      incorporation revealed synthesis of matrix proteoglycan by cartilage to be
      decreased 45, 59.7, and 37.5% after 1, 3, and 5 days, respectively, in culture in
      the presence of 5 U of IL-1/ml. There was no change in proteoglycan degradation
      as determined by measurement of [35S]O4 release into the culture medium. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis of cartilage-conditioned
      medium indicated that exposure of cartilage to IL-1 caused a decrease in total
      protein synthesis by 45, 68, and 87% after 1, 3, and 5 days, respectively, in
      culture while selectively inducing synthesis of the 57-kd neutral
      metalloproteinase stromelysin (matrix metalloproteinase-3) in young and adult
      horses. Identification of stromelysin was confirmed by functional
      characterization and immunoprecipitation. Baseline total protein synthesis, as
      well as specific synthesis of stromelysin in cartilage from adult and aged
      horses, was markedly less than that of young horses. The IL-1-induced reduction
      in total protein synthesis may not be a characteristic of equine articular
      cartilage from affected joints of horses with naturally acquired osteoarthritis
      as indicated by an overall increase in protein synthesis by osteoarthritic
      explants. Introduction of IL-1 into an equine articular cartilage explant culture
      system resulted in decrease of matrix component synthesis and increase in
      specific degradative enzyme synthesis and activity. Articular cartilage from aged
      horses had markedly less overall metabolic activity, compared with cartilage from
      young horses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141487
TI  - Ultrasonographic examination of the ventral neck region in cows.
AB  - The position, dimensions, and structure of the thyroid gland, the portion of the
      esophagus in the neck, the cervical lymph nodes, and the major blood vessels of
      the neck were determined via ultrasonography in cattle. The left and right
      ventral neck regions of 30 healthy Swiss Braunvieh cows were examined
      ultrasonographically, using 3.5- and 5.0-MHz linear transducers and a 3.5-MHz
      convex transducer. The external jugular vein was situated directly beneath the
      skin in the upper and middle parts of the neck and 2.7 to 6.6 cm from the body
      surface in the lower part of the neck. In contrast, the common carotid artery was
      located further from the body surface along the entire ventral neck region;
      depending on the measuring point, this distance varied from 2.6 to 10.9 cm. The
      external jugular vein narrowed from caudad to craniad. The diameter of the common
      carotid artery remained fairly constant along its course in the ventral part of
      the neck and varied from 0.9 to 1.4 cm. The thyroid gland was identified via
      ultrasonography caudodorsal to the larynx. It appeared as an echogenic spindle
      shaped structure with finely granular echogenic pattern. The esophagus appeared
      as a band-shaped structure in longitudinal section, and it could be followed to
      the thoracic inlet. Its width increased from craniad to caudad, and mean +/- SD
      diameter was 2.9 +/- 0.23 cm. The medulla, hilus, cortex, and capsule of the
      cervical lymph nodes could be clearly differentiated via ultrasonography. Mean
      length and width of the left cervical lymph node were 3.0 +/- 0.45 and 1.8 +/-
      0.23 cm, respectively.

PMID- 8141489
TI  - Effect of dietary sodium intake on glomerular filtration rate in partially
      nephrectomized dogs.
AB  - Exogenous creatinine clearance rate was determined in 8 partially (approx 75%)
      nephrectomized dogs fed 2 concentrations of dietary sodium, beginning 9 weeks
      after partial nephrectomy was performed. In a double crossover design, dogs were
      then fed low-sodium diet (0.18% sodium on a dry-weight basis) or high-sodium diet
      (1.3% sodium on a dry-weight basis) in 2 sequences (L/H/L or H/L/H) for 3
      consecutive 4-week observation periods. Glomerular filtration rate (GFR) was
      measured by exogenous creatinine clearance before and after partial nephrectomy,
      and every 2 weeks during the experimental diet periods. Initial mean +/- SD GFR
      (3.76 +/- 0.78 ml/min/kg of body weight) decreased precipitously after
      nephrectomy (1.25 +/- 0.45 ml/min/kg); however, during the postnephrectomy and
      experimental diet periods, GFR gradually increased in all dogs to nearly half the
      prenephrectomy values (1.87 +/- 0.22 ml/min/kg). Significant differences in GFR
      were not observed when dogs were fed the L/H/L or the H/L/H sequence. Therefore,
      it was concluded that abrupt changes from high dietary sodium (1.3%) to
      restricted dietary sodium (0.18%), or vice versa, does not cause deterioration of
      renal function in dogs with moderate renal impairment. However, caution should be
      used in extrapolating these findings to dogs with clinically evident (azotemia,
      isosthenuria) renal failure.

PMID- 8141488
TI  - Cardiopulmonary effects of positioning pregnant cows in dorsal recumbency during
      the third trimester.
AB  - The uterine hemodynamic response to maternal positioning in dorsal recombency was
      evaluated in 7 conscious pregnant cows during the third trimester. Anesthetic or
      sedative drugs were not administered. Uterine artery flow was measured, using a
      previously implanted ultrasonic flow probe. Catheters implanted in the uterine
      artery and vein were used for measurement of blood pressure and for blood sample
      collections. Heart rate, systemic arterial pressure, uterine arterial blood flow,
      arterial and venous oxygen and carbon dioxide tensions, and pH were measured in
      cows in standing position. Cows were cast with ropes and positioned in dorsal
      recumbency, then measurements were repeated at 15 and 30 minutes. Compared with
      standing measurements, dorsal recumbency caused 50% increase in heart rate and
      44% increase in arterial blood pressure. Uterine artery flow did not change
      significantly. Despite increased ventilation, arterial oxygenation was reduced
      during dorsal recombency. There were minimal differences between measurements at
      15 and 30 minutes of dorsal recumbency.

PMID- 8141490
TI  - Effects of dietary sodium intake on blood pressure measurements in partially
      nephrectomized dogs.
AB  - Systolic, diastolic, and mean arterial blood pressure were measured by femoral
      artery puncture every other day in 2 groups (n = 4) of partially nephrectomized
      (approx 75%) dogs fed 2 concentrations of dietary sodium beginning 9 weeks after
      partial nephrectomy was completed. In a double crossover design, dogs were fed a
      low-sodium (0.18% sodium on a dry-weight basis) or high-sodium (1.3% sodium on a
      dry-weight basis) diet in 2 sequences (L/H/L or H/L/H) for 3 consecutive 4-week
      observation periods. Significant effect of sequence was found in dogs fed the
      L/H/L sequence, compared with those fed the H/L/H sequence. Systolic blood
      pressure was significantly (P < 0.05) increased in dogs fed the L/H/L sequence
      (175 +/- 16 mm of Hg), compared with dogs fed the H/L/H sequence (156 +/- 14 mm
      of Hg). Mean arterial blood pressure was higher, but not significantly different,
      for the L/H/L sequence (116 +/- 8 mm of Hg) vs the H/L/H sequence (109 +/- 6 mm
      of Hg). Significant difference in diastolic pressure was not observed between the
      L/H/L (86 +/- 10 mm of Hg) and H/L/H (86 +/- 10 mm of Hg) sequences. Restricted
      sodium intake (0.18% sodium on a dry-weight basis) was associated with moderate
      systolic hypertension in dogs with experimentally induced chronic renal disease.
      Acute fluctuations in dietary sodium intake had no apparent immediate effect on
      blood pressure in dogs with this mild to moderate degree of renal dysfunction.

PMID- 8141491
TI  - Estimation of glomerular filtration rate and evaluation of renal function in
      ferrets (Mustela putorius furo).
AB  - Three methods of determining glomerular filtration rate (GFR) were performed in
      adult ferrets, 9 months to 7 years old. Endogenous creatinine clearance was
      determined, using serum and urine creatinine values obtained during 24- and 48
      hour collection periods from 27 ferrets housed in metabolic cages. Creatinine and
      radiolabeled inulin were administered to 12 female ferrets by constant IV
      infusion during isoflurane-induced anesthesia. Serial 20-minute urine
      collections, together with serum samples obtained at the midpoint of urine
      collection, provided measures for clearance calculations of these substances.
      Mean +/- SD endogenous creatinine clearance in ferrets for metabolic cage
      collections was 2.50 +/- 0.93 ml/min/kg of body weight. There were no significant
      differences between the 24- and 48-hour clearance rates. Mean inulin clearance
      was 3.02 +/- 1.78, and mean exogenous creatinine clearance was 3.32 +/- 2.16
      ml/min/kg. Analysis of variance, using least-squared means adjustment, did not
      yield any significant differences between inulin and exogenous creatinine
      clearance rates. Exogenous creatinine clearance-to-inulin clearance ratio was
      0.99 +/- 0.46, and there was significant correlation between the 2 methods (r =
      0.82, P = 0.0001). Significant body temperature effects on inulin or exogenous
      creatinine clearance were not found. Infused inulin clearance, the generally
      preferred method for GFR calculation in mammalian species, was significantly (P =
      0.0069) higher in younger (3.65 ml/min/kg) vs older ferrets (2.29 ml/min/kg).
      Results of this study indicate that inulin clearance is an adequate measure of
      GFR in ferrets as it is in other species. Compared with inulin clearance,
      exogenous creatinine clearance also provides a reliable estimate of GFR in
      ferrets.

PMID- 8141492
TI  - Evaluation of a dosing method for studying ergonovine effects in cattle.
AB  - We evaluated the feasibility of using miniosmotic pumps as a way to continuously
      treat cattle with a singular ergot alkaloid (ergonovine) of known content, thus
      mimicking the natural fescue toxicosis disease state, but allowing study of
      specific alkaloid effects. Dosing animals with increasing amounts of ergonovine
      via miniosomotic pumps, followed by daily acquisition of plasma samples for high
      performance liquid chromatographic determination of the alkaloid, resulted in
      stepwise increases in plasma ergonovine concentration. However, despite the
      detectable blood concentration of ergonovine, calves did not have typical
      clinical signs of ergot alkaloid toxicosis. Similarly, serum prolactin
      concentration was unaffected by ergonovine in these cattle, implicating some
      other alkaloid of endophyte-infested fescue as causative of the usual prolactin
      suppressive response. The results confirm use of this animal dosing method to
      study biological effects of singular purified alkaloids of known amount, without
      bioavailability concerns. Thus, this dosing method will facilitate studies to
      determine the harmful effects of individual alkaloids found in toxic tall fescue,
      and ultimately, to alleviate their costly effects in cattle, horses, and other
      species.

PMID- 8141493
TI  - Analysis of physeal growth in dogs, using biplanar radiography.
AB  - Biplanar radiography was used to study normal growth of the left and right radius
      in 5 Beagles and growth of the left radius alone in 15 additional Beagles. We
      explored the applicability of this radiographic method in veterinary medicine by
      measuring the contribution to total radius length from each growth plate.
      Spherical tantalum markers (0.5 mm) were embedded in the proximal epiphysis,
      diaphysis, and distal epiphysis of each dog's radius at 10 weeks of age.
      Simultaneous biplanar radiographic views were obtained every 4 weeks until
      skeletal maturity was documented. A three-dimensional coordinate system was
      constructed allowing for measurement of growth (in millimeters). Resolution of
      the measuring system was 0.074 mm. Mean +/- SEM length of the skeletally mature
      Beagle's radius, as measured from proximal epiphyseal bead to distal epiphyseal
      bead, was 95.33 +/- 1.07 mm. The percentage of contribution to the total radius
      length from the proximal and distal growth plates was 36.76 and 64.73%,
      respectively, with 95% confidence interval of 2.29%. The percentage of
      contribution to radius length from the distal radial growth plate increased for
      each consecutive time segment, with the distal radial physis contributing 61.75%
      from 10 to 14 weeks of age and increasing to 70.22% from 22 to 26 weeks of age.
      Significant growth was not observed after 26 weeks of age. The period of most
      rapid growth was between 10 and 14 weeks of age. Biplanar radiography was
      accurate and precise in quantifying the relative contribution of the proximal and
      distal growth plate to radius length in Beagles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141494
TI  - Morphometric analysis of the foramen magnum in Pekingese dogs.
AB  - The size and shape of the foramen magnum were studied in skulls from 75 adult and
      5 juvenile Pekingese dogs. After maceration of the skulls, the height, width, and
      area of each foramen magnum were measured, and various skull indices were
      determined. The shape of the foramen varied from ovoid to rectangular and had a
      dorsal notch in all but 2 skulls. Prolapse of cerebellum or brain stem through
      the enlarged opening was prevented by a fibrous membrane covering the dorsal
      notch. Mean +/- SD area of the foramen was 138.1 +/- 26.1 mm2; its mean total
      height was 15.0 +/- 2.9 mm, and its mean maximal width was 13.3 +/- 1.1 mm.
      Statistically, variability in the area of the foramen was mainly correlated with
      total height of the foramen, including the dorsal notch. Total height of the
      foramen was not correlated with age or gender. The degree of dysplasia, notch
      index, and occipital index of each foramen magnum were determined. To allow a
      more accurate evaluation of the morphology of the foramen, the foramen magnum
      index, defined as the ratio between the maximal width and the total height of the
      foramen, was also computed. Mean +/- SD foramen magnum index was 91.8 +/- 17.1 in
      the adult Pekingese dogs. Foramen magnum index was not significantly correlated
      with age, but was significantly larger in male than in female dogs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141495
TI  - Intranasal administration of Pasteurella multocida toxin in a challenge-exposure
      model used to induce subclinical signs of atrophic rhinitis in pigs.
AB  - A challenge-exposure model was developed for dose-dependent induction of
      subclinical (moderate) atrophic rhinitis (AR) in conventionally raised Dutch
      Landrace and Large White pigs, about 4 weeks old. Under favorable climatic and
      housing conditions, pigs were intranasally challenge-exposed with Pasteurella
      multocida-derived toxin (Pm-T) 3 days after pretreatment by inoculation with 1%
      acetic acid. Pigs were challenge-exposed with 1 of the following Pm-T doses: 0
      (control), 5, 13, 20, or 40 micrograms of Pm-T/ml of phosphate-buffered saline
      solution (PBSS), 0.5 ml/nostril/d on 3 consecutive days. Five weeks after
      challenge exposure, subclinical (moderate) AR status was defined as intermediate
      conchal atrophy (grade 2 for ventral conchae on a 0 to 4 scale and grade 1 or 2
      for dorsal conchae on a 0 to 3 scale, respectively) and perceptible difference in
      change in brachygnathia superior (cBS) between control and challenge-exposed pigs
      between the beginning and end of the study. All Pm-T-exposed pigs had nasal
      damage that was dose-dependent. The higher Pm-T doses resulted in higher ventral
      conchae atrophy and dorsal conchae atrophy scores. The cBS increased with applied
      Pm-T dose, resulting in significant (P < 0.05) differences between controls (3.88
      mm) and the 13-, 20-, and 40-micrograms Pm-T-treated groups (7.77, 6.58, and 7.98
      mm, respectively). In response to the applied dose, weight gain per week for Pm-T
      exposed pigs was lower than that of controls after week 3 (P < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141496
TI  - Assessment of vertebral canal diameter and bony malformations of the cervical
      part of the spine in horses with cervical stenotic myelopathy.
AB  - Magnification of cervical radiographs prevents accurate interpretation of
      vertebral canal absolute minimum sagittal diameter (MSD) values and application
      of the established MSD values for diagnosis of cervical stenotic myelopathy
      (CSM). Variability in MSD determination in human beings, owing to radiographic
      magnification, is minimized by assessing a ratio of the vertebral canal diameter
      to the sagittal width of the vertebral body. This relative measurement technique
      improves the accuracy of diagnosis of cervical spinal stenosis in human beings.
      The MSD of the vertebral canal was determined in 50 horses with CSM and 50
      control horses, using a radiopaque marker method for correction of magnification.
      In addition, a ratio of the absolute MSD to the sagittal width of the vertebral
      body and a ratio of the absolute MSD to the length of the vertebral body were
      determined in 100 CSM-affected and 100 control horses. Response operating
      characteristic curve analysis of each method determined that the sagittal ratio
      method of canal diameter assessment provided the most accurate interpretation of
      cervical radiographs for diagnosis of CSM, with sensitivity and specificity of >
      or = 89% at each vertebral site. The accuracy of the ratio method, without
      consideration of bony malformation, supports the importance, and perhaps
      prerequisite, of generalized vertebral canal stenosis in the pathogenesis of CSM.
      Subjective evaluation of bony malformations from cervical radiographs of 100 CSM
      affected horses and 100 control horses indicated that CSM-affected horses have
      more severe bony malformation than do control horses. However, moderate to marked
      degenerative joint disease of the articular processes was frequently observed in
      control horses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141497
TI  - Low blood lead concentration associated with various biomarkers in household
      pets.
AB  - A former secondary lead smelter was in operation in Granite City, Ill, until the
      early 1980s. As a result, the surrounding area is heavily contaminated with lead.
      Soil concentrations as high as 5,000 ppm have been measured in prior studies.
      Because of growing concerns about health defects associated with low levels of
      lead exposure in human beings, a major study has been conducted on people living
      in the area. The study reported here was a corollary to the human exposure study.
      Lead concentration was determined in 84 dogs and 26 cats in the town and ranged
      between < 5 and 28 micrograms/dl. None of the dogs had clinical signs of lead
      poisoning. The CBC and serum biochemical values did not indicate many significant
      differences between dogs with a high (> or = 10 micrograms/dl) or low blood lead
      concentration (BLC). Hemoglobin concentrations were lower, and WBC counts were
      higher in dogs and cats with higher BLC, but they were still within reference
      ranges. Free erythrocyte protoporphyrin concentration was determined. Normal
      values appeared to be similar for dogs and cats. Only animals with BLC > or = 20
      micrograms/dl were found to have somewhat increased concentration of free
      erythrocyte protoporphyrin. delta-Aminolevulinic acid dehydratase activity was
      measured and found to be negatively correlated with BLC. The relation was strong,
      even at low BLC (5 to 10 micrograms/dl) in both species. Age or sex difference
      was not observed. Therefore, biological changes associated with low BLC were
      limited to BLC in the 10- to 30-micrograms/dl range.

PMID- 8141498
TI  - Reactivity of polyclonal human CD3 antiserum in lymphoid tissues of cattle,
      sheep, goats, rats and mice.
AB  - Polyclonal rabbit antiserum to human T-cell CD3 was used to study its reactivity
      in lymphoid tissues (lymph nodes, spleen, aggregated lymphoid follicles [Peyer's
      patches], thymus) of several animal species (cattle, sheep, goats, rats, and
      mice). Using a peroxidase-antiperoxidase technique on formalin-fixed and paraffin
      embedded tissues, immunoreactive cells were detected in T cell-dependent areas of
      the lymphoid tissues. Reactivity was high in all species tested, but mouse
      tissues had reduced reactivity, compared with the other species. To obtain a
      reaction, it was necessary to digest tissues with pronase before application of
      the immunocytochemical technique. Our results indicate that CD3 antiserum may
      specifically recognize T-lymphoid cells as it does in human lymphoid tissues and
      can be used as a marker to study physiologic and pathologic conditions of the
      lymphoid system of these species.

PMID- 8141499
TI  - Exacerbated onset of dysentery in swine vaccinated with inactivated adjuvanted
      Serpulina hyodysenteriae.
AB  - After oral challenge exposure with Serpulina hyodysenteriae-infected diced colon,
      fewer swine vaccinated with an experimental vaccine adjuvanted with mineral oil
      died (8 of 25 [32%]) than did nonvaccinated controls (6 of 15 [40%]), although
      the difference was not significant. However, onset and exacerbation of dysentery
      were accelerated in vaccinated swine because: 5 of the 8 dead vaccinated swine
      died before any of the nonvaccinates, which was significant (P < 0.01);
      vaccinated swine that died were observed to have more hemorrhage in the feces,
      colonic mucosa, and colonic lumen than did nonvaccinated swine; and the earlier
      diarrhea onset in vaccinates, the more days of hemorrhagic diarrhea (P < 0.05).
      Antibody titer in vaccinated swine immediately before challenge exposure that
      subsequently died was significantly (P < 0.05) higher than that in vaccinated
      swine that recovered. Of of the 30 swine vaccinated with the experimental
      vaccine, 20 had dispersed droplets of mineral oil at the site of vaccination in
      the neck muscles and 3 swine had purulent abscesses at the injection site. It was
      concluded that vaccination with the experimental vaccine for controlling swine
      dysentery was ineffective.

PMID- 8141500
TI  - Immunopathologic study and characterization of the phenotype of transformed cells
      in sheep with bovine leukemia virus-induced lymphosarcoma.
AB  - We used monoclonal antibodies and immunohistologic examination of lymph nodes, to
      elucidate the pathogenesis of lymphosarcoma induced by infection with bovine
      leukemia virus (BLV). The superficial cervical lymph nodes from 3 BLV-infected
      but apparently healthy sheep and 5 sheep with full-blown lymphosarcoma were
      examined. We also investigated the integration of bovine leukemia provirus by use
      of Southern blotting. In lymph nodes from sheep lacking clinical signs of
      infection, in which the provirus had been integrated at multiple sites in the
      genome, many large hypertrophic follicles were observed in the cortex. These
      follicles had germinal centers consisting of CD4+T cells and B cells that
      expressed surface IgM (sIgM) and major histocompatibility complex (MHC) class-II
      antigens, but not B cell-specific B2 molecule. The percentage of CD4+T cells in
      the cortex was significantly (P < 0.05) higher than that of the controls and
      sheep with lymphosarcoma. In all sheep with lymphosarcoma, the lymph nodes were
      completely destroyed by proliferating neoplastic cells, and in addition, small
      atrophic follicles, which consisted of normal B-cell marker-positive cells, were
      seen near the trabecula and the subcapsule. In these instances, neoplastic cells
      appeared to be a monoclonal population derived from a single CD5- B-cell lineage
      and to be classified as 2 types, CD5-CD4-CD8-B2+MHC class-II+sIgM+ and CD5-CD4
      CD8-B2+MHC class-II+sIgM-. Moreover, CD8+T cells infiltrated diffusely throughout
      the tumorous lymph nodes apart from the atrophic follicles, and CD4+ cells were
      observed around atrophic follicles. Both types of T cells were small-size, normal
      lymphocytes with round and noncleaved nuclei, and were apparently non-neoplastic
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141501
TI  - Differentiation of Mycoplasma hyopneumoniae, M flocculare, and M hyorhinis on the
      basis of amplification of a 16S rRNA gene sequence.
AB  - To differentiate Mycoplasma hyopneumoniae, the cause of mycoplasmal pneumonia in
      pigs, from M flocculare and M hyorhinis, an assay, using the polymerase chain
      reaction to amplify a segment of the 16S rRNA gene sequence, was developed. The
      assay was found to be useful for identification of field isolates, as well as for
      identification of laboratory-adapted strains. Amplification of DNA from M
      hyopneumoniae and M flocculare resulted in products of 200 and 400 base pairs,
      respectively. The DNA from M hyorhinis was not amplified. The assay was sensitive
      enough to detect as little as 1,000 genome equivalents of M hyopneumoniae and M
      flocculare DNA. Sensitivity was increased 100-fold by increasing the
      concentration of magnesium ion in the reaction buffer from 2 to 4 mM; however,
      DNA from M hyorhinis was also amplified under these conditions. The DNA from
      several walled bacteria and from other mycoplasmas was also tested, but none of
      these DNA samples was amplified, suggesting that the assay was specific for
      porcine mycoplasmas.

PMID- 8141503
TI  - Efficacy dosage titration of lufenuron against developmental stages of fleas
      (Ctenocephalides felis felis) in cats.
AB  - Thirty-two mixed-breed male and female cats were blocked by sex, arranged by body
      weight from greatest to least, and allocated to 4 groups of 8 (4 male, 4 female)
      cats, using random numbers. Cats in each of 3 groups were treated orally with a
      7% suspension formulation of lufenuron at dosage of 15, 30, or 45 mg/kg of body
      weight. Cats in the fourth group were treated orally with an excipient suspension
      without lufenuron. Cats were infested with newly emerged, unfed cat fleas
      (Ctenocephalides felis felis) on days -7 and -3 before treatment and at
      approximately weekly intervals after treatment. Flea eggs were collected from
      beneath each cat on selected days before and after treatment and placed in an
      artificial rearing medium. Flea eggs and medium were kept for 35 days in an
      insectary to determine effects of lufenuron or excipient suspension on emergence
      of adults of the F1 generation. Lufenuron was 100% effective in inhibiting
      development of C felis at all dosages for 11 days after treatment. Thereafter,
      efficacy exceeded 92% in all dosages groups. On day 32, when the study was
      terminated, efficacy for each of the dosage groups was: 15 mg/kg, 95.2%; 30
      mg/kg, 98.2%; and 45 mg/kg, 99.6%. Adverse reactions or side effects were not
      observed in cats, regardless of treatment dosage.

PMID- 8141502
TI  - Determination of calcium, phosphorus, and magnesium values in rib bones from
      clinically normal cattle.
AB  - Mean phosphorus (P) content in bovine rib bone was 102.9, 108.3, and 182.7 mg/g
      of bone on fresh, dry, and ash weight bases, respectively. Values for calcium
      (Ca) were 194.3, 203.7, and 344.6 mg/g, respectively, and for magnesium (Mg) were
      5.3, 5.5, and 9.4 mg/g, respectively. Mean percentage of ash in rib bone was
      59.12%. Expected concentrations of Ca, P, and Mg were determined on fresh, dry,
      and ash weight bases and for 3 age groups, 3 breeds, and bulls, females, and
      steers. On an ash weight basis, cattle 6 to 18 months old had 185.74 mg of P/g,
      372.52 mg of Ca/g, and 12.37 mg of Mg/g. Those 19 to 36 months old had 182.02 mg
      of P/g, 322.35 mg of P/g, and 8.09 mg of Mg/g. Those > 36 months old had 174.80
      mg of P/g, 340.36 mg of Ca/g, and 6.62 mg of Mg/g. Steers had 183.93 mg of P/g,
      352.73 mg of Ca/g, and 10.15 mg of Mg/g. Females had 178.47 mg of P/g, 320.28 mg
      of Ca/g, and 6.5 mg of Mg/g. Males had 176.15 mg of P/g, all on an ash weight
      basis. Dairy breeds were found to have 186.08 mg of P/g, 351.25 mg of Ca/g, and
      10.47 mg of Mg/g. Cattle of mixed breeding had 177.42 mg of P/g, 341.28 mg of
      Ca/g, and 6.54 mg of Mg/g. The Africander breed of beef cattle had 167.07 mg of
      P/g, all on an ash weight basis.

PMID- 8141504
TI  - [Prevalence of rheumatic manifestations in human immunodeficiency virus
      infection].
AB  - Various rheumatic manifestations have been reported in HIV infected patients, but
      the prevalence of these manifestations is not well known. Therefore, we have
      designed a prospective study to define the rheumatic manifestations in those
      patients. METHODS: 121 patients (stage IV of CDC classification) were assessed by
      physical examination and biological tests. RESULTS: arthralgia was found in
      12.4%; painful articular syndrome occurred in 4.1%; arthritis was present in
      6.6%; out of 8 cases of arthritis, only 2 had spondylarthropathy. The articular
      manifestations were mostly oligo- or polyarticular, rarely invalidating,
      sometimes recurrent. No septic arthritis, no myositis and only 1 case of
      vasculitis was found. Raynaud's phenomenon prevalence was 17.4%, 43% of which
      appeared after HIV seropositivity was known. Lacrymal hyposecretion assessed by
      Schirmer's test was found in 49.6%. However, this did not prove the existence of
      a Sjogren's syndrome as no histological examination was performed. Back pain
      reached 38.6%. Sciatic neuralgias were noted in 17.6%. Biological and
      immunological results were unspecific. Low levels of antinuclear antibodies were
      found in 11.1% cases. They were more frequently found when articular
      manifestations existed. A higher level of CD8 lymphocytes was also noted when
      articular manifestations were present. No statistical link existed between the
      different rheumatic manifestations. CONCLUSION: our results show that the
      prevalence of rheumatic manifestations in HIV infection is slightly increased
      (24.7%). This study is the first to emphasize the frequency of Raynaud's
      phenomenon and lacrymal hyposecretion in HIV patients.

PMID- 8141505
TI  - [Septicemia in patients with human immunodeficiency virus infection (excluding
      Mycobacteria). Apropos of 58 cases].
AB  - We reviewed the characteristics of 58 episodes of septicemia which occurred in 53
      HIV infected adults over a 30-month period. This cases represented 10.1% of HIV
      infected hospitalized patients. At the time of septicemia, 79.3% patients were at
      AIDS stage; mean CD4 count was 72/mm3. Nosocomial septicemia occurred
      significatively more often in patients with previous AIDS defining illness and in
      neutropenic patients (p < or = 0.05 and p < or = 0.001 respectively).
      Staphylococcus coagulase negative (n = 17), Staphylococcus aureus (n = 11) and
      Salmonella (n = 8) were the most common organisms. The source of infection was
      found more frequently in nosocomial septicemia than in community-acquired
      septicemia (78% versus 46%; p < 0.02), mainly intravenous catheter (60%).
      Staphylococcus aureus, AIDS stage and nosocomial septicemia have high fatality
      rates. Mortality was not higher than previously reported in the general
      population.

PMID- 8141506
TI  - [Changes in left ventricular function in patients with HIV infection at the IV
      stage without clinical sign of cardiac involvement].

PMID- 8141507
TI  - [Occurrence of myasthenia in HIV infection. 2 cases].

PMID- 8141508
TI  - [Latent primary ileal non-Hodgkin's malignant lymphoma in a patient with acquired
      immunodeficiency syndrome].

PMID- 8141509
TI  - [Pseudotumor mediastinal adenopathies of infectious origin in AIDS. Apropos of 2
      cases].

PMID- 8141510
TI  - [Cutaneous manifestations of cryptococcosis in patients with human
      immunodeficiency virus infection].

PMID- 8141511
TI  - Traumatic cutaneous and sub-cutaneous nocardiosis without dissemination in a
      patient with AIDS.

PMID- 8141512
TI  - Interview with Joachim Robert Kalden. What is going to happen tomorrow as far as
      DNA and anti-DNA antibodies are concerned?. Interview by P. Youinou.

PMID- 8141513
TI  - [Anatomo-clinical conference. Pitie-Salpetriere Hospital. Case no. 3--1993.
      Febrile myalgia and hypereosinophilia in a 59-year-old woman].

PMID- 8141514
TI  - [Neuromuscular manifestations of thyroid diseases].

PMID- 8141515
TI  - [The "OPIACE" system. Clinical and diagnostic approach of insomnia in adults].

PMID- 8141516
TI  - [Mycobacterium chelonei arthritis in an immunosuppressed patient. Efficacy of the
      treatment with clarithromycin].

PMID- 8141517
TI  - [Monoarthritis of the knee disclosing Lyme disease].

PMID- 8141518
TI  - [Joint chondrocalcinosis--Bartter's syndrome: a rare association].

PMID- 8141519
TI  - [Tendinopathy caused by ciprofloxacin with possible partial rupture of Achilles
      tendon].

PMID- 8141520
TI  - [A case of agranulocytosis caused by clozapine].

PMID- 8141521
TI  - [Confusion syndrome, myoclonus and treatment with pefloxacin].

PMID- 8141522
TI  - [Peripheral neuropathy related to benign monoclonal gammopathy. Treatment with
      high-dose intravenous human immunoglobins].

PMID- 8141523
TI  - [Celiac disease and dementia of rapidly fatal outcome].

PMID- 8141524
TI  - [Carotid dissection and homolateral paralysis of the 12th cranial nerve].

PMID- 8141525
TI  - [Cytomegalovirus pneumopathy in a non-immunosuppressed patient. Treatment with
      ganciclovir].

PMID- 8141526
TI  - Is there a relationship between autoantibodies and silicone-gel implants?
AB  - The present study was conducted to determine if 200 patients with silicone-gel
      implants demonstrated elevated levels of autoantibodies, compared with a similar
      group of 100 age-matched control subjects without breast implants. These results
      were then compared with 29 patients who had demonstrated implant rupture.
      Differences in the frequency of autoantibody levels were determined by the chi
      squared test. Differences in autoantibody titers were determined by Wilcoxon's
      signed rank test. Differences were considered significant with p > 0.05. The
      prevalence of a positive antinuclear antibody (ANA) test (dilution 1:100) in the
      200 patients with breast implants was 26.5% compared with 28% in the 100 control
      subjects. In 29 patients with implant rupture, only 17.2% tested ANA positive.
      These values were not significantly different. In addition, there were no
      significant differences between the ANA titers of positive patients in each
      group. In each of the three groups, all patients who tested ANA positive were
      analyzed to assess the frequency and titer of other autoantibodies, including
      anti-DNA, anti-cardiolipin, anti-SSA, anti-SSB, anti-SM, anti-RNP, and anti-Scl
      70. There were no significant differences between the frequency or titer of any
      of these autoantibody levels in each of the three groups of patients. These
      studies strengthen the concept that there is no conclusive evidence that silicone
      gel implants are related to the development of connective tissue disease.

PMID- 8141527
TI  - Analysis of lower extremity blood flow in the patient with peripheral vascular
      insufficiency: a guide for plastic surgeons.
AB  - Accurate assessment of lower extremity blood flow is critical in selecting
      appropriate therapy for patients with peripheral vascular disease and nonhealing
      wounds. Although physical examination provides an idea about the extent and
      significance of the disease, further evaluation, including both noninvasive and
      invasive studies, is routinely obtained. Appropriate studies will provide
      valuable information about the location and severity of disease, the need for
      revascularization before definitive wound coverage, and the likelihood of wound
      healing. A brief overview of vascular laboratory tests, highlighting the values
      and limitations of each, is presented here.

PMID- 8141528
TI  - A simple technique for repair of rectus sheath defects.
AB  - Several approaches for repair of diastasis recti during abdominoplasty and repair
      of rectus sheath defect during transverse rectus abdominis musculocutaneous flap
      harvest have been described. Although these have generally been effective, we
      feel our procedure to be advantageous. The method presented is quick, easy, and
      efficient. In addition, because a looped (double), monofilament suture is used, a
      stronger, more aesthetic repair is accomplished. This technique has been used in
      39 patients over a 25-month period. No recurrences of diastasis recti and no
      hernias have been observed. Furthermore, all patients remain without complaint.

PMID- 8141529
TI  - Just wine.

PMID- 8141531
TI  - Hypoxia: another issue to consider when timing cleft repair.
AB  - The factors influencing cleft repair are multiple and complex. A compromise must
      be achieved between facial growth, scarring, speech and language development, and
      psychological factors. However, one question remains unanswered. When is it
      safest in relation to the maturity of the respiratory control mechanisms? It was
      the aim of this pilot study to identify any problems with respiratory function
      after primary surgery. Of 39 patients, 42% were seen to have episodes of repeated
      hypoxemia of < 92% saturation associated with bradycardia beyond 48 hours
      postoperatively. The implication of the findings and future directions for
      research are discussed.

PMID- 8141530
TI  - Re: Asymmetrical hypersensitivity to bovine collagen.

PMID- 8141532
TI  - Nasal bones and pyriform apertures in blacks.
AB  - The nasal bones and pyriform apertures of 20 skulls were measured for length and
      width. There were 6 skulls from the Ashanti tribe in West Africa, 5 black
      American skulls, 5 skulls from Austria in northern Europe, and 4 American Indian
      skulls. The nasal bones were measured for length and width at the narrowest and
      widest portions and the pyriform apertures were measured for height and for width
      at the base, the mid section, and near the apex at the nasomaxillary suture line.
      The Ashanti nasal bones were the shortest with a length of 2.18 cm. They were the
      narrowest with mean widths of 0.47 and 0.83 cm. The Austrian nasal bones were the
      longest (mean, 3.02 cm). The mean widths were 0.68 and 1.11 cm. The Indian nasal
      bones had a mean height of 3.0 cm and were the widest with mean widths of 0.61
      and 1.28 cm. The measurements of the American black nasal bones fell between the
      Ashanti on the one hand, and the Austrian and Indian on the other, with a mean
      height of 2.79 cm and mean widths of 0.49 and 1.03 cm, reflecting the triethnic
      origin. The pyriform aperture in the Ashanti was oval whereas the white and
      Indian pyriform apertures were triangular. The black American pyriform apertures
      varied from oval to triangular, also reflecting the triethnic origin. The
      clinical implication of these differences in black rhinoplasty are discussed.

PMID- 8141533
TI  - Local fasciocutaneous flaps for olecranon coverage.
AB  - In 1989 we began to treat soft-tissue defects around the olecranon process with
      local fasciocutaneous flaps as our preferred method of treatment. These soft
      tissue defects are complications of bursitis, degenerative joint disease, and
      burns. They may also result from pressure necrosis over the olecranon in patients
      with impaired sensation. Because of the difficulty in treating these wounds a
      variety of local muscle, musculocutaneous, fasciocutaneous, distant, and free
      flaps have been described. Fasciocutaneous flaps have the advantage of using
      regional tissue in a single stage. Fasciocutaneous flaps around the elbow can be
      categorized as proximally or distally based. Proximally based flaps include the
      radial and ulnar forearm flaps as well as the posterior interosseous flap.
      Distally based flaps are based on upper elbow collaterals including the radial
      collateral artery, the middle collateral artery, and the anterior and posterior
      ulnar recurrent arteries. Eleven fasciocutaneous flaps were used in 10 patients
      with a follow-up of 1 to 3 years. All flaps survived and provided primary wound
      closure. Complications included 1 patient with recurrent ulceration after being
      healed for 6 months and 1 patient with a transient neuropraxia of the posterior
      interosseous nerve that resolved after 2 weeks. These flaps provide long-term
      stable coverage of olecranon wounds by using regional tissue with an acceptable
      donor site morbidity.

PMID- 8141534
TI  - Deep inferior epigastric perforator flap for breast reconstruction.
AB  - The ideal material for reconstruction of a breast is fat and skin. Most current
      methods of autogenous reconstruction use myocutaneous flaps. We investigated the
      feasibility of transfer of skin and fat from the lower abdomen without muscle
      sacrifice. The flap is based on one, two, or three perforators of the deep
      inferior epigastric vessels. The study will demonstrate both experimentally and
      clinically this original technique for breast reconstruction. Fifteen breasts
      have been successfully reconstructed with this technique. This technique has all
      of the advantages of the free transverse rectus abdominis myocutaneous flap with
      decreased possibility of ventral hernia or muscle weakness.

PMID- 8141535
TI  - Antitumor agents: extravasation, management, and surgical treatment.
AB  - We discuss our experience with antineoplastic drug extravasation. Between
      December 1988 and December 1990, 40 patients with cytostatic extravasation with
      lesions of varying seriousness were observed. In these patients, whenever
      possible, depending on the amount of time that elapsed since the accident and on
      the severity of the lesion, conservative therapy was done. The procedure
      consisted of local injection of a considerable amount of saline solution (20-90
      ml, depending on the site of extravasation) and topical occlusive applications of
      corticosteroids locally. In all patients this was sufficient to avoid tissue
      necrosis. Treatment of a few patients deviated from these procedures because
      surgery was performed that ranged from the simple excision of infiltrated tissue
      to a more complex procedure of free flaps. On the basis of our experience, we
      discuss the role of early surgery when preventive measures and drug therapy are
      insufficient because of drug effects at the tissue level. In this series we did
      not perform early surgery.

PMID- 8141536
TI  - The influence of radiotherapy and chemotherapy on regeneration at arterial
      microanastomoses: an experimental and clinical study.
AB  - The regeneration of anastomosed aortas after radiotherapy and chemotherapy was
      studied by light, scanning, and transmission electron microscopy in a rat model.
      At the ultrastructural level, it was observed that sublethal doses of these
      methods of cancer treatment did not severely block endothelial proliferation in
      the region of the microanastomosis. Based on the experimental results,
      myocutaneous free flap transfers were completed in patients with malignant tumors
      who had been undergoing radiotherapy and chemotherapy to cover defects resulting
      from their excision.

PMID- 8141537
TI  - Influence of occlusive and impregnated gauze dressings on incisional healing: a
      prospective, randomized, controlled study.
AB  - After elective surgery, 28 patients with 40 wounds were enrolled in a controlled
      clinical study to assess the effects of two different dressings on incisional
      healing. Patients served as their own control with one-half of each incision
      covered with an impregnated gauze (Xeroform) and the other half of the incision
      covered with a thin occlusive hydrocolloid dressing (DuoDerm Extra Thin CGF). All
      wounds were evaluated 2 to 3 days, 7 to 10 days, 4 weeks, and 7 months
      postoperatively. None of the incisions segments showed any evidence of infection.
      At the time of suture removal, the hydrocolloid dressing's ability to contain
      exudate, protect the wound, and facilitate mobility and personal hygiene were
      rated higher compared with the gauze-type dressing (p < 0.001, for all
      variables). At the 4-week visit, both the patient and the surgeon rated the scar
      segments covered with the hydrocolloid dressing better with respect to color,
      evenness, and suppleness (p < or = 0.04, for all variables). These differences
      were no longer apparent 7 months after surgery.

PMID- 8141538
TI  - The future of graduate medical education in plastic surgery. The Association of
      Academic Chairmen in Plastic Surgery.

PMID- 8141539
TI  - The surgical anatomy of the subcutaneous fascial system of the scalp.
AB  - The surgical anatomy of the fascial layers and vascularization of the scalp was
      studied by means of 11 bilateral cadaver dissections. This article is organized
      as follows: first, a description of the layers and fasciae of the scalp and their
      relationships with the main vascular structures, and then a description of the
      histological structure of the subgaleal fascia (composed of multiple connective
      vascularized sheets that glide over one another) and of its blood supply. In our
      dissections, we found the constant topographic distribution of the major
      perforant vessels to the subgaleal tissues as follows: in the temporal region,
      perforant vessels from the superficial temporal artery near and 10 to 14 cm above
      the zygomatic arch, where the superficial temporal artery leaves the surface of
      the galea to enter the superficial subcutaneous tissue, and in the fronto-parieto
      occipital region, many small perforant vessels evenly entering the subgaleal
      plane every 5 to 10 mm. These findings could lead to greater use of fascial or
      composite flaps from the scalp region.

PMID- 8141540
TI  - Familial multiple glomus tumors: report of a pedigree and literature review.
AB  - Glomus tumors are uncommon, benign soft tissue tumors that can occur in a
      familial or sporadic pattern. Only 15 pedigrees have been reported to date. We
      report a family with three generations developing multiple glomus tumors of the
      skin. Although controversy exists over pattern of inheritance, review of the
      published pedigrees plus this additional one suggests an autosomal dominant
      inheritance with incomplete penetrance and variable expressivity.

PMID- 8141541
TI  - Facial contour reconstruction in lipodystrophy using a double paddle dermis-fat
      radial forearm free flap.
AB  - Facial lipodystrophy is a relatively rare disease and very little has been
      reported concerning the reconstruction of this facial deformity compared with
      Romberg's disease. In this article we report a new surgical procedure using a
      double paddle radial forearm dermis--fat free flap. By using this unique flap, we
      could reconstruct soft tissue defects on both cheeks in a one-stage operation
      using one flap. In the previous conventional procedure, two flaps are required
      for the reconstruction of bilateral defects on the face. Therefore, we also made
      a comparison between our flap and the conventional flap with regard to their
      advantages and disadvantages. Although this is a limited experience, we think
      using this flap is a preferable method of treating facial lipodystrophy.

PMID- 8141542
TI  - An inferior rectus abdominis bridge flap for revascularization of an ischemic
      tongue.
AB  - Ablative surgery to completely eradicate cancer may injure or necessitate
      ligation of major vessels. Unplanned necrosis of intact adjacent tissues and/or
      organs may result due to insufficient blood supply. We report a case in which a
      free inferior rectus abdominis musculocutaneous flap was successfully used as a
      bridge flap. Reconstruction of a soft tissue defect as well as revascularization
      of an ischemic organ (the tongue) was simultaneously achieved with a single flap
      transfer. To the best of our knowledge, this is the first report of a free
      inferior rectus abdominis musculocutaneous flap used successfully as a bridge
      flap.

PMID- 8141543
TI  - [Surgical and metabolic aspects of liver transplantation for tyrosinemia].
AB  - Tyrosinemia represents a very small percentage of patients undergoing liver
      transplantation world-wide. This disease is endemic within our referral area
      however, one-third of the liver transplantations at our institution are done for
      this disease. Since 1986, 16 patients with tyrosinemia and 34 patients with
      various other indications (non-tyrosinemic) have undergone a total of 55 liver
      transplantation. The survival rate for tyrosinemic patients is 87%, compared to
      75% for non-tyrosinemic patients. Liver transplantation for hereditary
      tyrosinemia and other metabolic disorders without portal hypertension or previous
      portohepatic operations is notably easier to perform. Intraoperative blood loss
      was less, length of hospital stay was shorter and incidence of infections was
      lower in tyrosinemic than in non-tyrosinemic patients. Less than 10% of
      tyrosinemic patients had foci of hepatocellular carcinoma at the time of
      transplantation. For this reason, and while most patients with tyrosinemia will
      eventually require liver transplantation, our results do not support systematic
      early transplantation.

PMID- 8141544
TI  - [Right diaphragmatic paralysis after liver transplantation].
AB  - Right hemidiaphragm paralysis has been previously documented in patients after
      orthotopic liver transplantation (OLT) and it may contribute to the development
      of postoperative pulmonary problems. It has been postulated that a crush injury
      to the right phrenic nerve during OLT is the cause of dysfunction of the right
      hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury
      after OLT, we prospectively studied 51 adult liver recipients that we compared
      with twelve patients who underwent liver resection (LR) without suprahepatic vena
      cava clamping. We studied the diaphragm excursion by ultrasound, the pulmonary
      function tests and the transcutaneous phrenic nerve conduction. Righ phrenic
      nerve injury and hemidiaphragm paralysis occurred respectively in 79% and 38% of
      the liver recipients but not after LR. Conduction along the right phrenic nerve
      was absent in 53% of the patients and reduced in another 26%. Left phrenic nerve
      conduction and left hemidiaphragm excursion were normal in both groups. Liver
      recipients with no conduction in the right phrenic nerve had a significantly
      greater decrease in vital capacity in the supine position compared to those with
      some conduction (29% vs 14%; P < 0.001). However, neither the time on the
      ventilator or the hospital stay were significantly different between the two
      groups. Complete recovery of phrenic nerve conduction and diaphragm function may
      take up to nine months. Right phrenic nerve injury is common after OLT and causes
      right hemidiaphragm dysfunction.

PMID- 8141545
TI  - [Technique to minimize the incidence of hepatic artery thrombosis in pediatric
      liver transplantation].
AB  - Hepatic artery thrombosis is a life-threatening complication after pediatric
      liver transplantation. We reviewed our experience in 62 children who received 72
      liver transplant (69 whole grafts and 3 reduced-size grafts) between January 1984
      and December 1991. They ranged in age from 6 months to 16 years (mean 5.8 years).
      Fifteen children (22%) were under 2 years and 10 patients (14%) were between 2
      and 5 years. Forty-eight grafts in older children (age: 1-16 years, x = 7 years
      had an anastomosis between the donor hepatic/celiac artery and the recipient
      hepatic of splenic artery (A-A). Three thromboses occurred in this group for an
      incidence of 6.2%. Two others types of arterial reconstruction were used in 24
      children who were significantly younger (6-120 months, x = 47 months, p < 0.01).
      Eight grafts had an anastomosis between the donor celiac artery and the recipient
      aorta (A-Ao). No thromboses occurred in this group. Sixteen grafts were
      revascularized using a donor aortic conduit anastomosed to the recipient aorta
      (AC) with a 12.5% (2 to 16) incidence of thrombosis. The incidence of arterial
      thrombosis for the entire group was 6.9%. In conclusion, by using the recipient
      aorta for arterial reconstruction, a low incidence of hepatic artery thrombosis
      can be achieved even in the group of younger patients who are the highest risk
      for this complication.

PMID- 8141546
TI  - [Biliary complications in pediatric liver transplantation].
AB  - Biliary tract complications are reported in 15% to 20% of orthotopic liver
      transplantations (OLT). Since 1986, 55 OLT were done in 50 children with a mean
      age and weight of 5.6 years and 18.8 kg respectively. There were 28 (51%) reduced
      liver grafts (RLG) and 27 (49%) whole liver grafts (WLG). Since starting using
      RLG in 1988, 70% of transplantations have been RLG. Choledochocholedochostomy
      with a T-tube (CC) or choledochojejunostomy (CJ) were done in 25 (45%) and 30
      (55%) cases, respectively. The overall mortality was 19% with one death related
      to biliary problems. There were 14 biliary tract complications (25%) in 12
      patients including 7 leaks, 6 obstructions and one intrahepatic biloma. Leaks
      leading to bile peritonitis were managed with simple suture and drainage and were
      related to the T-tube (4, to the Roux-en-Y loop (2) and the transection margin of
      a RLG (1). Obstruction was documented in 6 cases, none of which were associated
      with hepatic artery thrombosis (HAT). Stenosis after CC reconstruction (3)
      required conversion to CJ. Two patients had revision of CJ because of kinking of
      the common bile duct and an anastomotic stricture 46 months after OLT. One
      patient developed a vanishing bile duct syndrome 4 months post-transplant and
      died while waiting for retransplantation. One patient had multiple episodes of
      cholangitis after HAT and was retransplanted. The rate of biliary complications
      was not influenced by neither the type of graft (RLG : 25% vs WLG : 25,9%) nor
      the type of biliary reconstruction(CC : 28% vs CJ : 23%).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8141547
TI  - [Colorectal cancers associated with ulcero-hemorrhagic rectocolitis. Detection of
      and prognosis for postoperative patients].
AB  - Between January 1976 and December 1986, 86 patients underwent surgery for
      colorectal adenocarcinoma (AC) complicating ulcerative colitis (UC) at Mayo
      Medical Center in Rochester, Minnesota. Seventy-two percent were men, contrasting
      with only 55% in the population operated for UC without AC during the same time
      period at the same institution (p = 0.001). The mean duration of UC symptoms was
      19.2 years. The diagnosis of cancer was established preoperatively in 65% of
      patients, while the remainder of patients, except for three (n = 30, 35%) were at
      high risk for cancer. A colonoscopy performed in 16 of those 30 patients less
      than six months prior to the operation did not detect cancer. Overall, cancer was
      either proven or highly suspected preoperatively in 96.5% of patients, while the
      sensitivity of colonoscopy was 78%. During the study period, histological tumor
      features, such as number of tumors, Dukes' stage, Broder's stage, and
      curative/palliative ratio, remained unchanged, and the five-actuarial survival of
      50% did not improve with time (p = 0.37). Multivariant analysis indicated that
      Dukes' stage and male gender were two poor prognosis factors. For patients with
      long-standing UC, we offer either proctocolectomy, possibly with ileal pouch-anal
      anastomosis, or surveillance colonoscopy, emphasizing their respective hazards
      and limitations.

PMID- 8141548
TI  - [Splenectomy by celioscopy. Experience of 20 cases].
AB  - We describe the clinical course of 20 patients considered for laparoscopic
      splenectomy. One patient was excluded on the basis of preoperative angiography
      findings and two (10.5%) were converted to open surgery. The first patient in the
      series was converted for a hemorrhagic incident and the eight patient, who had a
      34 cm spleen, for dissection difficulties. In the remaining 17 patients who
      successfully underwent laparoscopic splenectomy, no mortality was reported and
      there were four postoperative complications (23.5%). Mean operating time was 3 h
      40 min (135-300 min). After a mean postoperative stay of four days, all patients,
      except two, were back to normal activities within 2 weeks of hospital discharge.
      Preoperative splenic artery embolization was begun with the third patient and was
      found to significantly reduce operative blood loss and make the procedure easier
      to perform. Laparoscopic splenectomy has become our procedure of choice for
      elective removal of normal-sized or moderately enlarged spleens.

PMID- 8141549
TI  - [Video-assisted thoracoscopy and thoracic surgery: the first 50 patients].
AB  - We report our first full year of clinical experience with video assisted thoracic
      surgery. From September 1991 to October 1992, 50 patients were treated using
      endoscopic surgical techniques. There were 29 men and 21 women with a mean age of
      48 years, ranging from 17 to 76 years. Drainage and talc poudrage of pleural
      effusions, with or without pleurodesis, was done in 18 patients (36%),
      blebectomies with pleurectomy or pleural abrasion was done in 11 patients (22%),
      and 7 patients (14%) underwent wedge resections of pulmonary lesions. Four other
      patients (8%) underwent resections or biopsies of mediastinal tumors, and 3 (6%)
      pericardial windows were done for cardiac tamponade. Finally, one chest wall
      biopsy and one empyema drainage were carried out, and 5 thoracoscopies were
      limited to the exploration of the chest. Complications occurred in 5 patients
      (10%). There was one mortality. Video-assisted thoracic surgery is efficacious in
      the treatment of various thoracic diseases and associated with satisfactory
      results in selected patients.

PMID- 8141550
TI  - [Surgical treatment of pneumothorax in AIDS patients].
AB  - A retrospective review of the charts of 26 patients with the acquired
      immunodeficiency syndrome (AIDS) treated at the Hotel-Dieu de Montreal was
      performed. Patients presented a total of 37 pneumothoraces. Eleven cases were
      recurrent. Bilateral pneumothoraces were documented in three patients, most of
      them (17) were severe (> 75%). Pneumocystis carinii pneumonia was the most
      frequently associated pathology. The initial treatment consisted in chest tube
      drainage. A definitive treatment was indicated in 7 patients with prolonged air
      leaks (> 10 days) or without lung expansion. Two median sternotomies with
      bilateral pleurectomies, bullae plication, and talcage were done, and 5
      unilateral thoracotomies with pleurectomies and bullae plications were completed.
      The post-operative survival was variable and related to diseases associated with
      the syndrome. AIDS related pneumothoraces is a morbid condition which should be
      treated on an individual basis.

PMID- 8141551
TI  - [Effect of different solutions of preservatives on the endothelial function of
      coronary arteries in rats].
AB  - The effects of cold storage and type of preservation solution on coronary
      endothelial function are not well established. Experiments were designed to
      evaluate coronary endothelial-dependent relaxation after a 4-hour cold (4 degrees
      C) storage in different preservation solutions. Rat hearts, mounted in the
      Langendorff apparatus, were arrested with a 10-minute perfusion of 4 degrees C
      crystalloid hyperkaliemic cardioplegic solution (CHCS) (KCl 24 mEq/l) and stored
      for 4 hours in the following preservation solutions: CHCS (n = 6), Krebs-Ringer
      solution (KR) (n = 6), 0.9% NaCl (NS) (n = 6) and the University of Wisconsin
      solution (UW) (n = 6). A fifth group (n = 6) was perfused and stored in UW
      solution. Endothelium-dependent and independent coronary artery vasorelaxations
      were respectively tested by infusing 5-hydroxytryptamine (5-HT) (10(-6) mol/l)
      and sodium nitroprusside (SNP) (10(-5) mol/l) before and after the storage
      period. In hearts stored with CHCS or KR, coronary artery flow increase to 5-HT
      and SNP infusions were not significantly affected. However, in hearts preserved
      with NS or UW solutions, 5-HT coronary response was significantly decreased,
      indicating endothelial dysfunction. In addition to these findings, coronary flow
      increase to SNP infusion was decreased in the group perfused and stored with UW,
      suggesting smooth muscle dysfunction. These experiments suggest that 4-hour cold
      storage in NS or UW impairs endothelial-dependent coronary relaxation in the
      isolated rat heart model.

PMID- 8141552
TI  - [Place of gastroepiploic and epigastric arteries in myocardial
      revascularization].
AB  - Seventy patients underwent coronary artery bypass grafting with the right
      gastroepiploic artery or the inferior epigastric artery between 1989 and 1992 at
      the Montreal Heart Institute. There were 68 men and 2 women with a mean age of 53
      +/- 8 years, the right gastroepiploic artery in situ was anastomosed to the right
      coronary artery in 55 patients and the inferior epigastric artery (free graft)
      was used in 18 patients. Double internal thoracic artery grafts were used in all
      patients. Early patency rate of right gastroepiploic artery and inferior
      epigastric artery grafts was 91% (31/34 grafts) and 57% (8/14 grafts)
      respectively. One patient died after surgery (1.4%) from acute renal failure and
      one patient developed an acute myocardial infarction (1.4%) at surgery. Fifty
      five patients (55/57, 96%) showed no evidence of angina at the last follow-up. In
      conclusion, patency rate and clinical results of coronary artery bypass grafting
      with the right gastroepiploic artery graft were excellent and patency rate of
      inferior epigastric artery graft was unsatisfactory. We suggest that epigastric
      artery grafts should be used with caution, only when no other alternative is
      available.

PMID- 8141553
TI  - [Magnetic resonance imaging in the diagnosis and follow-up of false aneurysms
      after Bentall's operation].
AB  - The prevalence and natural history of pseudo-aneurysm (PA) following Bentall
      procedure has not been established. To determine the follow-up of such patients,
      we report our experience with magnetic resonance imaging (MRI) used since 1988.
      At first, spin-echo exam, PA was suspected in 19 patients among 27 patients who
      underwent aortic valve and ascending aortic replacement between 1980 and 1991.
      Mean PA diameter was < 4 cm in 13 patients (group 1) and > or = 4 cm in six
      patients (group 2). Two patients of group 1 were lost at follow-up while two
      others died after the first spin-echo exam, one death being related to PA
      formation. Repeated MRIs were done in nine patients of group 1 and all patients
      of group 2 averaging respectively 2.2 +/- 1.1 exams per patient for group 1 and
      1.8 +/- 1.1 for group 2. PA regressed in six patients of group 1 and one patient
      of group 2 thus suggesting thrombosed PA or postoperative haematoma. PA remained
      stable in two patients of group 1 and one patient of group 2. One patient of
      group 1 in whom PA increased at follow-up died suddenly. Four patients of group 2
      required surgical correction of their PA. One of these patients died of massive
      hemoptysis 2 months following reintervention. Recently, addition of cine MRI
      allows visualization of turbulent flow within the PA thus increasing MRI
      specificity for PA diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141554
TI  - [Morphological study of the innervation of spinal ligaments in scoliotic
      patients].
AB  - The purpose of this study was to investigate the morphology of nerve endings in
      spinal ligaments of scoliotic and normal patients. Nervous elements were
      investigated by means of gold chloride (AuCl2) impregnation and an indirect
      avidine-biotine peroxydase immunohistochemical method. Antiserum to a
      neurofilament protein (NFP) and S-100 protein were used as specific markers of
      nervous elements. In scoliotic and normal patients, immunohistochemical staining
      demonstrated a rich innervation of inter- and supra-spinous ligaments as compared
      to the yellow ligament. The immunohistochemical staining is however the most
      convenient and specific mean for studying the innervation in the ligaments. These
      two staining methods did not show any morphological difference in nervous
      elements of scoliotics ligaments as compared to the normal ligaments. These
      findings confront the role of the posterior ligamentous system in proprioception
      essential both in static and dynamic function of the sepine. However, the
      degeneration of neural elements in spinal ligaments could be involved in the
      etiology of the idiopathic scoliosis.

PMID- 8141555
TI  - [Culture of fibroblasts of canine anterior cruciate ligaments in a defined
      medium, effect of epidermal growth factors and platelet derived growth factors].
AB  - Wounded ACL heal very poorly. Following ligament rupture, the initial scar tissue
      is highly unorganized and is mechanically and biochemically very different from
      the normal tissue. As fibroblasts play the main part in ligament healing and
      remodelling process, we try to construct a model of fibroblast's response to
      various environmental conditions. This type of model would provide a solid ground
      for improving therapies. A fibroblast strain has been isolated from canine ACL. A
      totally defined, serum-free medium has been optimized for that strain. We adapted
      and modified the common techniques, using radio-isotopes, for quantifying DNA,
      collagen and proteoglycan synthesis. Dose-response curves obtained by these
      methods are given for Epidermal Growth Factors and Platelet Derived Growth
      Factors. Both factors are mitogenic, PDGF more so than EGF. Collagen production
      is affected by neither, while PG synthesis is down-regulated by PDGF.

PMID- 8141556
TI  - [Biomechanical simulation of the effect of the Boston brace on a model of the
      scoliotic spine and thorax].
AB  - A biomechanical model was developed to investigate the immediate effect of the
      Boston brace on the spine and thorax of two scoliotic patients (12 year old
      females with identical lumbar curves of 37 degrees and thoracic curves of 32
      degrees and 25 degrees). This model is an improvement of Stokes model and
      incorporates several modifications concerning the modelling of costo-vertebral
      and costo-transverse joints. Forces generated by braces on the thorax were
      measured by pressure sensors and used as input into the finite element model. The
      deformed models were compared to the geometry of the same patients wearing their
      brace and with Stokes model. Concordance of results supports the modelling
      method. Differences between Stokes and improved models were observed. However,
      because of the small amount of patients included in this study, it is not
      possible to conclude on the effect of the modelling improvements.

PMID- 8141557
TI  - [Relationship between osteochondromas of the forearm in children and dislocation
      of the radial head].
AB  - Since treatment of a dislocated radial head is difficult in the growing child, we
      looked for risk factors associated with dislocated radial head in a group of
      patients with forearm osteochondromas. This is a retrospective study of 21
      patients with a mean age of 7.7 years. We measured forearm bone length, size of
      the osteochondromas, ulnar variance at the wrist, radial articular angle and
      determined radial head localization. The severity of ulnar shortening was
      associated with radial head localization (p < 0.005). Ulnar shortening caused by
      ulnar osteochondromas larger than 0.20 of total ulnar length was associated with
      radial head dislocation (p < 0.001). Early treatment of ulnar shortening in this
      group might prevent the radial head from dislocating.

PMID- 8141558
TI  - [Mitchell's osteotomy in the treatment of hallux valgus].
AB  - Ninety-one (91) Mitchell osteotomies on 63 patients (60 females and 3 males) were
      reviewed. The average follow-up was 40 months (min. 12, max. 70). The average age
      at the time of the surgery was 51 years (min. 20, max. 74). The presence of a
      apinful bunion justified the surgery in a majority of cases (92%). The clinical
      evaluation was done by an independent observer. Weight bearing X-rays of the feet
      were made in each case. The results show a satisfactory improvement of the pain
      in 92% of the cases. The patients were satisfied with the appearance of their
      foot in 93% of the cases. The average active articular range of motion was 47
      degrees (min. 20 degrees, max. 120 degrees). The Das De scale showed 75% of
      excellent and good results. Twelve per cent (12%) of the patients presented
      residual metatarsalgia. We observed minor complications in 10 cases (11%). We
      report no cases of avascular necrosis, pseudarthrosis or infection. Clinico
      radiological correlations were made. We obtained an average correction of 13
      degrees (min. -5 degrees, max. 28 degrees) of the hallux valgus and 3.5 degrees
      (min. -7 degrees, max. 7 degrees) of the intermetatarsal angle. We recommend the
      Mitchell osteotomy as long as the indication criterias and the surgical technique
      are respected.

PMID- 8141559
TI  - [Non-cemented self-locking total arthroplasty of the hip. Clinical and
      radiological results after three years].
AB  - We reviewed 47 patients who had fifty-one (51) primary, cementless biofit total
      hip arthroplasties (THA) implanted at Maisonneuve-Rosemont Hospital between 1986
      and 1990. An independent observer rated the patients on the Harris Hip Score
      (HHS) by questionnaire, physical examination and radiological assessment. The
      average follow-up was 40 months. Twenty-two percent (22%) of the femoral
      components had been revised because of incapacitating pain, limping or a HHS
      inferior to 60. A little more than 20% of the unrevised prostheses had a mediocre
      result (HHS inferior to 70). There was no correlation between results and
      radiological signs of instability. The femoral component of the hip arthroplasty
      has a poor clinical performance which compares unfavourably with cemented
      prostheses.

PMID- 8141560
TI  - [Comparative biomechanical evaluation of the immediate stability of three
      fixators in arthrodesis of the ankle].
AB  - The best type of osteosynthesis for ankle arthrodesis is controversial.
      Arthrodesis was performed on 21 cadaveric ankles using either the T-plate
      compression device, crossed cancellous-bone screws or the Charnley external
      fixator. The instrumented ankles were tested in five degrees of freedom. Internal
      fixation was more stable. More specifically, the compression T-plate was the most
      stable, and the Charnley external fixator was the least stable, for all degrees
      of freedom tested. In addition to the multiple clinical advantages of internal
      fixation, the results of our study support its use as a method of obtaining the
      most stable immediate fixation for ankle arthrodesis.

PMID- 8141561
TI  - Central nervous system-immune system interactions: psychoneuroendocrinology of
      stress and its immune consequences.
AB  - Psychoneuroimmunology is a relatively new discipline which deals with CNS-immune
      system interactions. The evidence for such interactions was reviewed, as was the
      neuroendocrinologic response to stress. Recent evidence indicates that the
      behavioral, nervous system, and neuroendocrine responses to stress are mediated
      by hypothalamic CRF, which acts on both the sympathetic nervous system and the
      HPA axis, resulting in increased levels of corticosteroids, catecholamines, and
      certain opiates, substances which are generally immunosuppressive. Concentrations
      of growth hormone and prolactin, which are immunoenhancing, are elevated early
      during the response to stress but are later suppressed. Although several other
      neuromediators may also be released with stress, the net effect of a variety of
      acute stressors is down regulation of the immune system function. In the
      following minireview, I consider whether stress alters the resistance of the host
      to infection as well as the immunomodulatory effects of released immune system
      mediators on the brain.

PMID- 8141562
TI  - Sequence analysis of PER-1 extended-spectrum beta-lactamase from Pseudomonas
      aeruginosa and comparison with class A beta-lactamases.
AB  - We have determined the nucleotide sequence (EMBL accession number, Z 21957) of
      the cloned chromosomal PER-1 extended-spectrum beta-lactamase gene from a
      Pseudomonas aeruginosa RNL-1 clinical isolate, blaPER-1 corresponds to a 924-bp
      open reading frame which encodes a polypeptide of 308 amino acids. This open
      reading frame is preceded by a -10 and a -35 region consistent with a putative P.
      aeruginosa promoter. Primer extension analysis of the PER-1 mRNA start revealed
      that this promoter was active in P. aeruginosa but not in Escherichia coli, in
      which PER-1 expression was driven by vector promoter sequences. N-terminal
      sequencing identified the PER-1 26-amino-acid leader peptide and enabled us to
      calculate the molecular mass (30.8 kDa) of the PER-1 mature form. Analysis of the
      percent GC content of blaPER-1 and of its 5' upstream sequences, as well as the
      codon usage for blaPER-1, indicated that blaPER-1 may have been inserted into P.
      aeruginosa genomic DNA from a nonpseudomonad bacterium. The PER-1 gene showed
      very low homology with other beta-lactamase genes at the DNA level. By using
      computer methods, assessment of the extent of identity between PER-1 and 10 beta
      lactamase amino acid sequences indicated that PER-1 is a class A beta-lactamase.
      PER-1 shares around 27% amino acid identity with the sequenced extended-spectrum
      beta-lactamases of the TEM-SHV series and MEN-1 from Enterobacteriaceae species.
      The use of parsimony methods showed that PER-1 is not more closely related to
      gram-negative than to gram-positive bacterial class A beta-lactamases.
      Surprisingly, among class A beta-lactamases, PER-1 was most closely related to
      the recently reported CFXA from Bacteroides vulgatus, with which it shared 40%
      amino acid identity. This work indicates that non-Enterobacteriaceae species such
      as P. aeruginosa may possess class A extended-spectrum beta-lactamase genes
      possibly resulting from intergeneric DNA transfer.

PMID- 8141563
TI  - In vitro selective antibiotic concentrations of beta-lactams for penicillin
      resistant Streptococcus pneumoniae populations.
AB  - Therapeutic regimens containing beta-lactam antibiotics are selecting penicillin
      resistant Streptococcus pneumoniae populations all over the world. The selective
      pressure after 4 h of exposure to different concentrations of amoxicillin,
      cefixime, cefuroxime, and cefotaxime for low-level or high-level penicillin
      resistant S. pneumoniae was evaluated in an in vitro model with mixed populations
      with penicillin susceptibilities of 0.015, 0.5, 1, and 2 micrograms/ml. The
      antibiotic concentration selecting for low-level resistance strongly reduced the
      susceptible population. Increasing antibiotic concentrations tended to decrease
      the total proportion of penicillin-resistant bacteria because of reduced numbers
      of the low-level-resistant population. The antibiotic concentration selecting for
      high-level resistance produced fewer resistant populations, but most of the
      organisms selected represented high-level resistance. In general, amoxicillin was
      a good selector for the low-level-resistant population and a poor selector for
      high-level resistance; cefuroxime and cefotaxime were poor selectors for low
      level resistance and better selectors than amoxicillin for high-level penicillin
      resistance. Cefixime was the best selector of low-level penicillin resistance.
      When only resistant populations were mixed, the strains with high-level
      resistance were selected even at low antibiotic concentrations. Determination of
      the effects of selective antibiotic concentrations on mixed cultures of bacteria
      expressing different antibiotic resistance levels may help researchers to
      understand the ecology and epidemiology of penicillin-resistant S. pneumoniae
      populations.

PMID- 8141564
TI  - Effect of mycophenolic acid on Epstein-Barr virus infection of human B
      lymphocytes.
AB  - The effect of mycophenolic acid (MPA) on the growth of Epstein-Barr virus (EBV)
      transformed B cells and on EBV lytic-cycle gene expression was investigated. MPA
      inhibited the proliferation of newly infected or established EBV-transformed B
      cell lines but was not able to block cell growth transformation or the viral
      lytic cycle. These results suggest that MPA might reduce transformed-cell
      proliferation in transplant patients and possibly decrease the risk of
      development of EBV-related lymphoproliferative disorders.

PMID- 8141565
TI  - Novel aspect of amphotericin B action: accumulation in human monocytes
      potentiates killing of phagocytosed Candida albicans.
AB  - The influence of low doses of amphotericin B on the capacity of human monocytes
      to kill Candida albicans was investigated. Killing rates were quantified by a
      novel flow cytometric assay and were found to be 37% +/- 3% (standard error of
      the mean) after 3 h. Preincubation of monocytes for 6 to 20 h with low
      concentrations of amphotericin B (0.2 microgram/ml) resulted in a markedly
      augmented fungicidal capacity. Enhancement of killing was 80% +/- 11% (standard
      error of the mean) over that by the controls. This effect did not appear to be
      due to amphotericin B-dependent monocyte activation; the respiratory burst and
      expression of human leukocyte antigen-DR were unaltered, and no stimulation of
      interleukin-1 beta release occurred. Cell-associated amphotericin B was extracted
      with acetonitrile and was quantified by scanning spectrophotometry. Amphotericin
      B appeared to accumulate in the cells, and intracellular concentrations attained
      after overnight incubation in 1 microgram of the drug per ml were estimated to be
      in the range of 50 fg per cell. The fact that intracellular accumulation was
      responsible for the enhanced fungicidal capacity of monocytes was supported by
      the findings that killing of Staphylococcus aureus remained normal and
      enhancement of killing of an amphotericin B-resistant C. albicans strain was
      minimal. Dramatic enhancement of monocyte fungicidal capacity probably extends to
      other amphotericin B-susceptible fungi and could represent a hitherto
      unrecognized determinant underlying the curative properties and prophylactic
      efficacy of this drug.

PMID- 8141566
TI  - Placement of alkyl substituents on the C-7 piperazine ring of fluoroquinolones:
      dramatic differential effects on mammalian topoisomerase II and DNA gyrase.
AB  - Several substituted analogs of 7-(cis-3,5-dimethylpiperazinyl)-6,8-difluoro-5
      amino-1-cyclopropyl quinolone were prepared and tested in a DNA cleavage assay
      with calf thymus topoisomerase II. Positioning of the methyl groups on the C-7
      piperazine ring influenced potency against the mammalian enzyme; the cis-3,5
      dimethyl configuration did not stimulate cleavage at drug concentrations less
      than or equal to 2,000 microM, while the trans configuration was active at drug
      levels as low as 36 microM. Removal of the cis-methyl groups produced a compound
      that was only sixfold less potent than the antitumor agent etoposide in
      stimulating enzyme-mediated DNA cleavage. The cis- and trans-methyl substitutions
      on the piperazine that conferred potency against the mammalian type II enzyme had
      little effect on bacterial DNA gyrase cleavage activity, suggesting that an
      asymmetric barrier exists with the mammalian enzyme which influences productive
      quinolone interaction, favoring the less bulky trans-3,5-dimethylpiperazine
      substituent at C-7.

PMID- 8141567
TI  - In vitro susceptibilities of rapidly growing mycobacteria to newer antimicrobial
      agents.
AB  - The in vitro antimicrobial susceptibilities of 42 isolates of rapidly growing
      mycobacteria (Mycobacterium fortuitum, M. chelonae, and Mycobacterium species
      [other than M. fortuitum and M. chelonae]) to nine quinolones, including newer
      agents, two new aminoglycosides, and an aminocyclitol (trospectomycin) were
      determined by a broth microdilution method. The new quinolones, PD 117596, PD
      127391, and PD 117558, showed excellent in vitro activities against M. fortuitum
      (MICs for 90% of isolates [MIC90s], 0.06, 0.06, and 0.12 microgram/ml,
      respectively). The MIC90 of ciprofloxacin for M. fortuitum was 0.5 microgram/ml.
      Only 14 to 28% of isolates of M. chelonae were susceptible to various quinolones.
      Most isolates of all three species were susceptible to the new aminoglycosides
      SCH 21420 and SCH 22591. The MIC90s of trospectomycin were 8 micrograms/ml for M.
      chelonae, 32 micrograms/ml for Mycobacterium species, and > 64 micrograms/ml for
      M. fortuitum.

PMID- 8141568
TI  - Interaction between clarithromycin and biofilms formed by Staphylococcus
      epidermidis.
AB  - Interactions between clarithromycin and biofilms formed by Staphylococcus
      epidermidis were investigated by using a clarithromycin-resistant strain.
      Treatment of the colonization with a relatively low concentration of
      clarithromycin resulted in the eradication of slime-like structure and a decrease
      in the quantity of hexose. Another result was increased penetration of
      antibiotics through the biofilm of S. epidermidis.

PMID- 8141569
TI  - Antimicrobial susceptibility of Arcanobacterium haemolyticum.
AB  - The susceptibilities of 138 clinical isolates of Arcanobacterium haemolyticum to
      11 antimicrobial agents were tested. All strains were susceptible to
      phenoxymethylpenicillin, cephalosporins, erythromycin, azithromycin, clindamycin,
      vancomycin, doxycycline, and ciprofloxacin but were resistant to trimethoprim
      sulfamethoxazole.

PMID- 8141570
TI  - Comparative activities of piperacillin and tazobactam against clinical isolates
      of Legionella spp.
AB  - We evaluated the in vitro activity of piperacillin alone or in combination with
      the beta-lactamase inhibitor tazobactam against clinical isolates of Legionella
      species. At an inoculum of approximately 10(4) CFU, tazobactam, piperacillin, and
      the 8:1 combination had equivalent activities against Legionella spp. At an
      approximately 10-fold higher inoculum, the following results were obtained,
      expressed as MICs for 50 and 90% of strains tested (MIC range): piperacillin, 4
      and 16 (0.25 to 32) micrograms/ml; tazobactam, 0.5 and 1 (0.125 to 2)
      micrograms/ml; and piperacillin-tazobactam (expressed in terms of MIC of
      piperacillin) 0.5 and 1 (0.03 to 2) micrograms/ml. Tazobactam alone and the
      combination with piperacillin were more active than piperacillin alone at the
      higher inoculum.

PMID- 8141571
TI  - Treatment of Klebsiella pneumoniae septicemia in normal and leukopenic mice by
      liposome-encapsulated muramyl tripeptide phosphatidylethanolamide.
AB  - The effect of free muramyl tripeptide phosphatidylethanolamide (MTPPE) and
      liposome-encapsulated MTPPE (LE-MTPPE) on Klebsiella pneumoniae septicemia
      resulting from intraperitoneal bacterial inoculation was investigated in mice.
      When administering a single prophylactic dose at 24 h before bacterial
      inoculation, the percentage survival was 55% (MTPPE) or 40% (LE-MTPPE), whereas
      untreated control mice died. Only repeated prophylactic treatment with LE-MTPPE
      could further increase survival up to 85%.

PMID- 8141572
TI  - Pharmacokinetics of meropenem in patients with intra-abdominal infections.
AB  - Noncompartmental and compartmental analyses of meropenem disposition in patients
      receiving 1-g intravenous intermittent infusions every 8 h were performed. Twelve
      patients (one woman and 11 men) participated in the meropenem pharmacokinetic
      analysis. Operative findings included perforated appendicitis (five patients),
      gangrenous appendicitis (five patients), peri-appendical abscess (one patient),
      and gunshot wound to the abdomen (one patient). The most common associated
      adverse drug reactions to meropenem were diarrhea and increased liver enzymes.
      The estimated noncompartmental pharmacokinetic parameters, mean +/- standard
      deviation, are as follows: maximum drug concentration in plasma, 47.58 +/- 17.59
      micrograms/ml; half-life, 1.04 +/- 0.19 h; elimination rate constant, 0.68 +/-
      0.12 h-1; area under the concentration-time curve from 0 h to infinity, 57.5 +/-
      20.12 micrograms x ml/h; total plasma clearance, 315.40 +/- 71.94 ml/min; renal
      clearance, 136.7 +/- 89.20 ml/min; volume of distribution at steady state, 26.68
      +/- 6.88 liters; and mean residence time, 1.47 +/- 0.28 h. The two-compartment
      model best described meropenem disposition in our patients. Our findings differed
      from estimates for healthy volunteers possibly because of the physiologic changes
      as a result of surgery. Our findings suggest that meropenem (1,000 mg)
      administered intravenously every 8 h provides adequate concentrations for most
      intra-abdominal infections.

PMID- 8141573
TI  - Antimicrobial susceptibilities of Neisseria gonorrhoeae strains representing five
      distinct resistance phenotypes.
AB  - The susceptibilities of 109 strains of Neisseria gonorrhoeae to penicillin G,
      tetracycline, amoxicillin-clavulanic acid, cefotetan, cefoxitin, ceftriaxone,
      ciprofloxacin, and fleroxacin were determined. The activities of cefmetazole,
      cefuroxime, cefixime, and ofloxacin were also determined against 62 of these
      strains. Strains represented penicillin-susceptible (Pen(s)) N. gonorrhoeae;
      penicillinase-producing N. gonorrhoeae (PPNG) possessing 2.9-, 3.05-, 3.2-, or
      4.4-MDa beta-lactamase plasmids; strains with high-level, plasmid-mediated
      tetracycline resistance (TRNG); strains with plasmid-mediated resistance to
      penicillin and tetracycline; and strains with chromosomally mediated resistance
      to penicillin and tetracycline (CMRNG). Ceftriaxone, cefixime, and ciprofloxacin
      were the most active agents tested against all strains. Pen(s), TRNG, and PPNG
      strains possessing a 3.2-MDa beta-lactamase plasmid were more susceptible to
      amoxicillin-clavulanic acid, extended- and broad-spectrum cephalosporins, and
      quinolones than were either PPNG strains possessing a 2.9-, a 3.05-, or a 4.4-MDa
      beta-lactamase plasmid or CMRNG strains.

PMID- 8141574
TI  - Retain intermittent dosing of carbapenems.

PMID- 8141575
TI  - Recombinant virus assay: a rapid, phenotypic assay for assessment of drug
      susceptibility of human immunodeficiency virus type 1 isolates.
AB  - Antiviral drug susceptibility assays for clinical human immunodeficiency virus
      type 1 (HIV-1) isolates are required to monitor the development of drug
      resistance during clinical trials and antiretroviral drug therapy. First
      generation phenotypic assays possess a number of drawbacks, not least the
      selection of unrepresentative virus populations during cocultivation. Here we
      describe a rapid phenotypic assay for the assessment of the susceptibility of
      clinical isolates to reverse transcriptase (RT) inhibitors. This procedure,
      called the recombinant virus assay, allows the generation of viable virus by
      homologous recombination of a PCR-derived pool of RT coding sequences into an RT
      deleted, noninfectious proviral clone, pHIV delta BstEII. A nested PCR procedure
      has been optimized to allow the amplification of an RT pool from both uncultured
      and cocultured infected patient peripheral blood lymphocyte (PBL) DNA for
      subsequent use in the creation of recombinant viruses. Analysis of two patients
      during the course of zidovudine therapy showed that this approach produced
      viruses which accurately exhibited the same genotype and phenotype as that of the
      original infected PBL DNA. The recombinant virus assay can be performed in
      approximately 3 weeks without the use of donor PBLs and therefore represents a
      rapid, nonselective procedure for the assay of clinical isolates.

PMID- 8141576
TI  - Comparison of mutants of Toxoplasma gondii selected for resistance to
      azithromycin, spiramycin, or clindamycin.
AB  - Azithromycin and spiramycin markedly inhibited the growth of Toxoplasma gondii in
      cultured human fibroblasts. However, 3 days of treatment were required to reveal
      their full antitoxoplasma activity. This delayed onset of inhibition was similar
      to that previously reported for clindamycin. Mutants of T. gondii resistant to
      azithromycin (AziR-1) and spiramycin (SprR-1) were isolated and compared with a
      previously described mutant resistant to clindamycin (ClnR-2). Mutant ClnR-2 was
      cross-resistant to all three antibiotics, while AziR-1 was cross-resistant only
      to spiramycin and SprR-1 was cross-resistant only to azithromycin. In short-term
      studies of protein synthesis by freshly prepared extracellular parasites,
      clindamycin and azithromycin were effective only at concentrations much greater
      than their 50% inhibitory concentrations in infected cultures and the resistant
      mutants did not differ from the wild type in antibiotic sensitivity. Thus,
      protein synthesis on cytoplasmic ribosomes of the parasite did not seem to be the
      target of these antibiotics. To determine whether mitochondrial protein synthesis
      in T. gondii was inhibited by clindamycin or azithromycin, wild-type parasites
      were grown in cultured cells in the presence of antibiotic concentrations well
      above the 50% inhibitory concentrations. Mitochondrial function, measured by
      oxygen uptake per purified extracellular parasite, did not decrease
      substantially, after the parasites had multiplied 11-fold in the presence of
      antibiotic. Thus, mitochondrial protein synthesis did not seem to be the target
      of clindamycin or azithromycin. An alternative target is protein synthesis in the
      putative apicomplexan organelle that has a 35-kb genome.

PMID- 8141577
TI  - Effect of foscarnet induction treatment on quantitation of human cytomegalovirus
      (HCMV) DNA in peripheral blood polymorphonuclear leukocytes and aqueous humor of
      AIDS patients with HCMV retinitis. The Italian Foscarnet Study Group.
AB  - The aim of this study was to investigate peripheral blood polymorphonuclear
      leukocytes and, whenever possible, aqueous humor from 65 AIDS patients with
      ophthalmoscopically diagnosed human cytomegalovirus (HCMV) retinitis to determine
      (i) whether patients consistently carry viral DNA and (ii) to what extent
      foscarnet induction treatment decreases viral DNA levels. HCMV DNA was quantified
      by PCR using densitometric analysis of hybridization products obtained from
      external standards and a standard curve from which the number of genome
      equivalents of test samples, normalized by using an internal amplification
      control, was interpolated. Results showed that 56 of 65 patients (86.1%) were
      positive for HCMV DNA prior to induction treatment. Of 41 of the 56 patients
      (73.2%) whose blood had become DNA negative after induction, only 5 had a high
      viral load (> 5,000 genome equivalents per 2 x 10(5) polymorphonuclear
      leukocytes) prior to induction, whereas as many as 13 of the 15 (26.8%) patients
      remaining DNA positive after induction had a high viral load prior to induction.
      Finally, of the nine patients (13.8%) with DNA-negative blood prior to induction
      treatment, three were shifted to foscarnet from ganciclovir, while six were
      erroneously enrolled in the study. Pre- and postinduction aqueous humor samples
      were obtained from 12 patients; all of these were DNA positive prior to
      induction, whereas after induction, 4 became negative, 6 showed a marked decrease
      in viral DNA, and 2 had nearly stable low DNA levels. In conclusion, PCR is a
      valuable tool for etiologic diagnosis and monitoring of HCMV retinitis treatment
      in AIDS patients. HCMV DNA is consistently present in the blood and aqueous humor
      of all patients with HCMV retinitis. Foscarnet induction treatment is highly
      effective in suppressing or reducing DNA levels in both blood leukocytes and
      aqueous humor.

PMID- 8141578
TI  - Improved medium for fluconazole susceptibility testing of Candida albicans.
AB  - We have compared fluconazole susceptibilities of 92 clinical isolates of Candida
      albicans by broth microdilution in two different media: standard RPMI 1640 (RPMI)
      and the same medium supplemented with 18 g of glucose per liter (RPMI-glucose).
      Preparation of media, drugs, and inocula, as well as incubation conditions,
      followed the preliminary recommendations of the National Committee for Clinical
      Laboratory Standards (Villanova, Pa.) antifungal agent working group for broth
      macrodilution tests with antifungal agents, adapted to microdilution. Microtiter
      plates were agitated for 5 min before spectrophotometric readings were performed
      with an automatic plate reader set at 405 mm. The MIC endpoint was defined as an
      inhibitory concentration calculated from the turbidimetric data as a function of
      the turbidity in the drug-free control wells. The mean absorbances in the drug
      free wells in RPMI and RPMI-glucose were, respectively, 0.38 (41.6% transmission)
      and 0.99 (10.2% transmission) (P < 0.001; Student's t test). Despite the
      increased growth in RPMI-glucose, 98.9% of the C. albicans strains tested for
      fluconazole susceptibility yielded similar MICs (+/- 1 dilution) in both media.
      Moreover, strains with decreased susceptibility to fluconazole displaying similar
      MICs in both media are easier to detect in RPMI-glucose because of the greater
      differences between turbidimetric readings in wells with grown or fluconazole
      inhibited cultures. This objective turbidimetric method, with an easy-to-read
      improved medium (RPMI with glucose), together with previous experience of the
      National Committee for Clinical Laboratory Standards antifungal agent
      subcommittee, could overcome some of the present problems associated with lack of
      reproducibility of azole susceptibility testing.

PMID- 8141579
TI  - Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae
      that are oxacillin resistant and penicillin susceptible.
AB  - It has recently been reported that penicillin-sensitive pneumococci may exhibit
      reduced susceptibility to oxacillin, resulting in their misclassification as
      being penicillin resistant by oxacillin disk testing. Intermediate oxacillin
      resistance (MIC, 1.0 microgram/ml) in three of these apparently unrelated
      penicillin-susceptible clinical isolates of Streptococcus pneumoniae isolated in
      the United Kingdom and in four Spanish isolates was shown to be solely due to the
      acquisition of a gene encoding an altered penicillin-binding protein (PBP),
      PBP2X. PBP2X genes cloned from typical penicillin-resistant isolates of S.
      pneumoniae that possessed high-level oxacillin resistance were shown to be able
      to transform susceptible isolates of S. pneumoniae to intermediate oxacillin
      resistance. In all instances, the intermediately oxacillin-resistant PBP2X
      transformants retained susceptibility to penicillin (MIC, 0.06 microgram/ml).
      Under appropriate selective pressure, the acquisition of a low-affinity PBP2X by
      penicillin-susceptible pneumococci could result in an increasing number of false
      positives for penicillin resistance among isolates of S. pneumoniae screened with
      oxacillin. Additionally, these intermediately oxacillin-resistant isolates showed
      reduced susceptibility to cefotaxime, an agent likely to be prescribed in place
      of penicillin for the treatment of serious infections due to these apparently
      penicillin-resistant organisms.

PMID- 8141580
TI  - Temporal changes of pharmacokinetics, nephrotoxicity, and subcellular
      distribution of tobramycin in rats.
AB  - The present study was designed to determine the temporal changes in tobramycin
      nephrotoxicity during the dark and the light periods of the day and to look for
      the mechanisms of such changes. Female Sprague-Dawley rats (9 to 11 weeks old)
      were housed in a 14-h-light-10-h-dark cycle (lights on 0600 to 2000 h). A bolus
      of tobramycin (60 mg/kg of body weight) was intravenously injected into a first
      group of 15 rats, at either 1400 or 0200 h. Six blood samples were taken from
      each rat, 30 to 210 min after the bolus injection. The total clearance of the
      drug was reduced during the rest period (1400 h) of rats compared with the
      activity period (0200 h) (P = 0.0007). Another group of 99 rats was given
      intraperitoneally a single dose of tobramycin (40 mg/kg), and renal cortices were
      collected 2 to 222 h after injection. The cortical drug levels were always higher
      in animals injected at 1400 h than in those injected at 0200 h. A last group of
      32 rats was used in the studies of tobramycin (30 mg/kg/day, once daily for 10
      days, intraperitoneally) nephrotoxicity and subcellular distribution. Weight gain
      in the rats receiving tobramycin (both 1400 and 0200 h) was significantly (P =
      0.028) less than that in the controls. Nephrotoxicity, indicated by the
      incorporation of [3H]thymidine into cortical DNA and urinary excretion of N
      acetyl-beta-D-glucosaminidase, was significantly higher in animals treated at
      1400 h than in those treated at 0200 h. No difference in the subcellular
      distribution of tobramycin was observed. The data indicate that the reduction in
      the clearance of tobramycin during the rest period is in part responsible for the
      higher nephrotoxicity in rats.

PMID- 8141581
TI  - Clinical trial of sparfloxacin for lepromatous leprosy.
AB  - Nine previously untreated patients with lepromatous leprosy were treated with 200
      mg of sparfloxacin daily for 12 weeks to determine whether this drug is
      bactericidal for Mycobacterium leprae in humans. The efficacy of therapy was
      monitored both clinically and by measuring changes in morphological index, mouse
      footpad infectivity, and the radiorespirometric activity of M. leprae organisms
      obtained from serial biopsy specimens and also by determining titers of phenolic
      glycolipid-I in serum. Most patients showed clinical improvement within 2 weeks
      of treatment; this was accompanied by significant reductions in the morphological
      index, mouse footpad infectivity, and bacillary radiorespirometric activity.
      After 4 weeks of treatment, all patients had a morphological index of zero and
      specimens from most patients were noninfectious for mice, while the median
      decrease in radiorespirometric activity was > 99%. Overall results by the rapid
      radiorespirometric assay paralleled those of the mouse footpad and morphological
      index assays. Sparfloxacin given at 200 mg once daily appears to be rapidly
      bactericidal in humans, with activity similar to that observed in a previous
      clinical trial with 400 mg of ofloxacin.

PMID- 8141582
TI  - In vitro selection of human rhinovirus relatively resistant to soluble
      intercellular adhesion molecule-1.
AB  - Variants of human rhinovirus serotype 39 (HRV-39) relatively resistant to
      inhibition by soluble intercellular adhesion molecule-1 (sICAM-1) were selected
      by serial passages in HeLa or WI-38 cells in the presence of sICAM-1. Moderate
      resistance (four- to fivefold increases in 50% effective inhibitory
      concentrations [EC50s]) was observed after the second passage in HeLa cells and
      remained constant during six further passages in the presence of 10 micrograms of
      sICAM-1 per ml. A 7- to 17-fold increase in EC50s was observed in WI-38 cells
      during passage with 10 micrograms/ml, and reversion to a nonresistant phenotype
      was not observed after four passages in the absence of sICAM-1. Resistance of a
      higher degree was obtained by passing HRV-39 in the presence of 100 micrograms of
      sICAM-1 per ml in HeLa cells (30-fold EC50 increase). The sICAM-1-resistant
      phenotype was estimated to constitute 1 in 10(4) to 1 in 10(5) PFU of a
      nonexposed HRV-39 population. Low to moderate levels of resistance to sICAM-1
      inhibition emerge readily during in vitro passage in the presence of sICAM-1 and
      appear to be phenotypically stable.

PMID- 8141583
TI  - Immune system-central nervous system interactions: effect and immunomodulatory
      consequences of immune system mediators on the brain.
AB  - A bidirectional circuit exists between the central nervous system and the immune
      system, since activation of the immune system results in the elaboration of
      cytokines and inflammatory mediators; these mediators induce hypothalamic CRF,
      which stimulates the release of the same immunosuppressive molecules that mediate
      the response to stress. The brain, therefore, is likely to be involved in immune
      system regulation. Hypofunctioning of the HPA axis with insufficient down
      regulation may be involved in autoimmune or other diseases with excessive immune
      system activation. Hyperfunctioning of the HPA axis, which is not appropriately
      suppressed, has been found in a large number of patients with major depression.
      Evidence that stress is an important factor in both lowering resistance to
      infectious agents and contributing to the reactivation of latent viruses is
      discussed. Also discussed is the evidence that stress induces proinflammatory
      cytokines which may contribute to both the pathogenesis of inflammatory diseases
      of unknown etiology and the progression of HIV infection to AIDS by activation of
      HIV replication.

PMID- 8141584
TI  - Molecular characterization of an enterobacterial metallo beta-lactamase found in
      a clinical isolate of Serratia marcescens that shows imipenem resistance.
AB  - A clinical isolate of Serratia marcescens (TN9106) produced a metallo beta
      lactamase (IMP-1) which conferred resistance to imipenem and broad-spectrum beta
      lactams. The blaIMP gene providing imipenem resistance was cloned and expressed
      in Escherichia coli HB101. The IMP-1 was purified from E. coli HB101 that harbors
      pSMBNU24 carrying blaIMP, and its apparent molecular mass was calculated to be
      about 30 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Kinetic studies of IMP-1 against various beta-lactams revealed that this enzyme
      hydrolyzes not only various broad-spectrum beta-lactams but also carbapenems.
      However, aztreonam was relatively stable against IMP-1. Although clavulanate or
      cloxacillin failed to inhibit IMP-1, Hg2+, Fe2+, or Cu2+ blocked the enzyme's
      activity. Moreover, the presence of EDTA in the reaction buffer resulted in a
      decrease in the enzyme's activity. Carbapenem resistance was not transferred from
      S. marcescens TN9106 to E. coli CSH2 by conjugation. A hybridization study
      confirmed that blaIMP was encoded on the chromosome of S. marcescens TN9106. By
      nucleotide sequencing analysis, blaIMP was found to encode a protein of 246 amino
      acid residues and was shown to have considerable homology to the metallo beta
      lactamase genes of Bacillus cereus, Bacteroides fragilis, and Aeromonas
      hydrophila. The G+C content of blaIMP was 39.4%. Four consensus amino acid
      residues, His-95, His-97, Cys-176, and His-215, which form putative zinc ligands,
      were conserved in the deduced amino acid sequence of IMP-1. By determination of
      the amino acid sequence at the N terminus of purified mature IMP-1, 18 amino acid
      residues were found to be processed from the N terminus of the premature enzyme
      as a signal peptide. These results clearly show that IMP-1 is an enterobacterial
      metallo beta-lactamase, of which the primary structure has been completely
      determined, that confers resistance to carbapenems and other broad-spectrum beta
      lactams.

PMID- 8141585
TI  - Effects of polyaspartic acid on pharmacokinetics of tobramycin in two strains of
      rat.
AB  - To provide insight into polyaspartic acid nephroprotection and differences in
      aminoglycoside renal toxicity between two rat strains, the single-dose
      pharmacokinetics of tobramycin was examined in the presence and absence of
      polyaspartic acid. Following a single subcutaneous 6.5-mg/kg dose of tobramycin
      alone, higher aminoglycoside concentrations were measured in Sprague-Dawley rats
      than in Fischer rats (P < 0.05). Simultaneous administration of polyaspartic acid
      (50 mg/kg) and tobramycin did not alter the concentrations of tobramycin in
      serum. The amount of tobramycin in renal tissue and the amount recovered in urine
      over a 24-h period were greater in both rat strains when tobramycin and
      polyaspartic acid were given concomitantly. In summary, polyaspartic acid did not
      alter the concentrations in serum achieved after a single dose of tobramycin in
      two different rat strains but did result in higher renal concentrations and
      greater urinary excretion of tobramycin.

PMID- 8141586
TI  - In vivo pharmacokinetics and pharmacodynamics of topical ketoconazole and
      miconazole in human stratum corneum.
AB  - A direct study evaluating whether differential drug uptake of topical 2%
      miconazole and 2% ketoconazole from cream formulations into human stratum corneum
      correlated with differential pharmacological activity against Candida albicans
      was investigated in healthy human subjects. A single 24-h topical dose of 2%
      ketoconazole cream or 2% miconazole cream was applied unoccluded, at the same
      dose (2.6 mg of formulation per cm2 of surface area), at four skin sites on both
      ventral forearms of six human subjects. At the end of the treatment, residual
      drug was removed with a tissue from all sites and the treated site was tape
      stripped 11 times, either 1, 4, 8, or 24 h later. The first tape disc was
      discarded. The remaining tape discs, 2 through 11, were combined and extracted
      for drug quantification by high-performance liquid chromatography and bioactivity
      against C. albicans growth in vitro. Topical 2% ketoconazole produced 14-, 10-,
      and 7-fold greater drug concentrations in stratum corneum than 2% miconazole at
      1, 4, and 8 h after a single topical dose. Ketoconazole and miconazole
      concentrations in the stratum corneum were similar 24 h after drug removal. Tape
      disc extracts from 2% ketoconazole-treated skin sites demonstrated significantly
      greater bioactivity in the bioassay than 2% miconazole. The increased efficacy of
      2% ketoconazole compared with that of 2% miconazole in vitro reflects their
      differential uptake into the stratum corneum and inherent pharmacological
      activity. Tape stripping the drug-treated site in conjunction with a bioassay is
      therefore a useful approach in the determination of bioavailability of topical
      antifungal agents.

PMID- 8141587
TI  - In vitro antiplasmodial, antiamoebic, and cytotoxic activities of a series of
      bisbenzylisoquinoline alkaloids.
AB  - Twenty-four bisbenzylisoquinoline alkaloids were screened for antiplasmoidal,
      antiamoebic, and cytotoxic activities by use of in vitro microtests. Eight of the
      alkaloids had antiplasmodial activity, with a 50% inhibitory concentration (IC50)
      of less than 1 microM against a multidrug-resistant strain of Plasmodium
      falciparum (chloroquine had an IC50 of 0.2 microM). The three alkaloids most
      active against Entamoeba histolytica, aromoline, isotrilobine, and insularine,
      had IC50s of 5 to 11.1 microM (metronidazole had an IC50 of 1.87 microM). None of
      the 24 bisbenzylisoquinoline alkaloids exhibited significant cytotoxicity against
      the KB cell line, the most toxic being berbamine, with an IC50 of 17.8 microM
      (the IC50 of podophyllotoxin was 0.008 microM). Bisbenzylisoquinoline alkaloids
      merit further investigation as potential novel antimalarial agents.

PMID- 8141589
TI  - A rapid and reliable assay for testing acyclovir sensitivity of clinical herpes
      simplex virus isolates independent of virus dose and reading time.
AB  - The determination of acyclovir (ACV) sensitivity of clinical herpes simplex virus
      (HSV) isolates was studied by means of a cytopathic effect (CPE) inhibitory assay
      (CIA). Medium of HSV-infected Vero cells was supplemented with different ACV
      concentrations. The CPE was read quantitatively by light microscopy. The
      inhibitory dose for 50% CPE reduction (ID50) was calculated by applying 1st or
      3rd degree regression lines, and aspects of different methods for calculation are
      discussed. The CIA proved highly reproducible. Surprisingly, the obtained ACV
      ID50 values were independent of reading time and virus dose used in the test. In
      comparison to dye-uptake assay, CIA could be evaluated earlier. Therefore, CIA
      provides simple, rapid, and precise determination of ACV sensitivity of clinical
      HSV-isolates which can be achieved within 1 or 2 days after the virus has been
      isolated out of a clinical specimen.

PMID- 8141588
TI  - The role of RSV neutralizing antibodies in the treatment and prevention of
      respiratory syncytial virus infection in high-risk children.
AB  - Studies assessing the use of RSV immune globulin in the treatment of RSV illness
      are not yet completed. However, a large multicenter trial demonstrated that
      prophylaxis with RSV immune globulin was safe and efficacious in prevention of
      serious RSV disease in high-risk infants. Refinements in the practical
      application of RSVIG are needed, as intravenous lines are difficult to place and
      maintain in these fragile infants. With the development of concentrated
      polyclonal and/or effective monoclonal antibody preparations, it may be possible
      to immunize intramuscularly (Tempest et al., 1993; Barbas et al., 1992). The
      efficacy of RSV-specific monoclonal antibodies must still be defined, and the
      appropriate viral epitopes targeted. While these issues still need to be
      addressed, it is exciting to have finally produced a safe and effective way to
      prevent severe RSV disease in high-risk young children.

PMID- 8141590
TI  - Antiviral treatment of Argentine hemorrhagic fever.
AB  - Argentine hemorrhagic fever is a systemic viral disease caused by Junin virus,
      with a mortality of 15-30% in untreated individuals. Current specific therapy is
      highly effective in reducing mortality, and consists of the early administration
      of immune plasma in defined doses of specific neutralizing antibodies per kg of
      body weight. However, several reasons suggest the need to investigate alternative
      therapies. Ribavirin, a broad spectrum antiviral agent, is effective in the
      treatment of other viral hemorrhagic fevers, and the studies done with Junin
      virus infections to date indicate that this drug may also have a beneficial
      effect in Argentine hemorrhagic fever.

PMID- 8141591
TI  - A slow release formulation for recombinant bovine interferon alpha I-1.
AB  - Recombinant bovine interferon-alpha I1 (rBoIFN-alpha) has known antiviral and
      immunomodulatory effects which have been exploited to reduce clinical disease in
      a number of clinical situations including bovine respiratory diseases. A slow
      release rBoIFN-alpha formulation may be of value to reduce bovine respiratory
      disease under field conditions by extending the period of protection, and hence
      improving the prophylactic benefits of rBoIFN-alpha. In this report, we describe
      a formulation of rBoIFN-alpha in sesame oil containing calcium stearate which can
      successfully sustain the release of rBoIFN-alpha over an 8-day period.
      Recombinant bovine IFN-alpha could be measured in serum for 8 days following
      treatment with an initial burst of release 6 h after injection. After a single
      subcutaneous depot injection of 50 mg and 100 mg of rBoIFN-alpha, initial serum
      levels reached 12-15 ng/ml and 25 ng/ml respectively. Correlating with this burst
      of release, there was a decrease in the number of circulating CD4-CD8- gamma
      delta+ T lymphocytes, and a slight neutropenia. No alterations in other cell
      phenotypes tested (CD4, CD8, CD2, CD6, B cells, monocytes or MHC class II) were
      observed, nor were there changes in lymphokine activated killer (LAK), natural
      killer (NK) cell activity, or oxygen radical formation (assessed by reduction of
      nitroblue tetrazolium). However, despite the rapid and short-lived burst of
      rBoIFN-alpha, levels of 2-5 oligoadenylate (2-5 A) synthetase remained elevated
      for 8 days. The sustained increase of 2-5 A synthetase was not due to the high
      initial dose released during the burst 6-12 h after injection, since injection of
      a bioavailable equivalent dose of interferon induced a significant rise in 2-5 A
      synthetase activity for 4 days only. As 2-5 A synthetase is known to be a
      correlate of antiviral activity, we propose that this formulation of rBoIFN-alpha
      may be one approach to increase the window of protection, leading to more
      effective prevention of bovine respiratory disease.

PMID- 8141592
TI  - The in vitro anti-hepatitis B virus activity of FIAU [1-(2'-deoxy-2'-fluoro-1
      beta-D-arabinofuranosyl-5-iodo)uracil] is selective, reversible, and determined,
      at least in part, by the host cell.
AB  - A human hepatoblastoma cell line was stably transfected with a head-to-tail dimer
      of the Hepatitis B virus (HBV), subtype adw, genome to generate a cell line which
      produces HBV. FIAU [1-(2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl-5
      iodo)uracil] inhibited viral replication in these cells with an IC50 of 0.90
      microM, as determined by PCR analysis of extracellular Dane particle DNA, and
      displayed a 50% cytotoxic concentration (TC50) of 344.3 microM, as determined
      using the MTT assay. The selectivity index of FIAU (TC50/IC50) was 382.6. In
      cells incubated for 10 days with FIAU (100 microM) and then incubated with drug
      free media with daily media changes for 7 days, viral DNA replication was
      markedly inhibited but resumed within 24 h after drug removal, demonstrating that
      the in vitro anti-HBV activity of FIAU is reversible. Both the antiviral activity
      and cytotoxicity of FIAU were reversed by the addition of equimolar to 10-fold
      excess molar concentrations of thymidine. The de-iodinated metabolite of FIAU,
      FAU, had only marginal anti-HBV activity at 100 microM, indicating that this
      metabolite does not contribute significantly to the activity of FIAU. The
      examination of intracellular viral DNA replicative intermediates revealed that
      FIAU was 2000-fold more active against duck HBV DNA replication in human hepatoma
      cells (IC50 = 0.075 microM) than against this same virus in chicken liver cells
      (IC50 = 156 microM). FIAU was anabolized to a 25-fold greater extent in human
      hepatoma cells than in chicken cells, indicating that the anti-HBV activity of
      this nucleoside analog is dependent, in part, on its phosphorylation by the host
      cell.

PMID- 8141593
TI  - Studies on mechanism of action of glycyrrhizin against hepatitis A virus
      replication in vitro.
AB  - Glycyrrhizin (GL) achieved a concentration-dependent inhibition of the
      replication of hepatitis A virus (HAV) in PLC/PRF/5 cells. GL has been shown to
      inhibit an early stage of the HAV replication. GL was not virucidal and had no
      measurable effect on the adsorption of [3H]uridine-labelled virions to cells. GL
      inhibited HAV penetration of the plasma membrane as measured by the amount of
      infective virus no longer neutralizable by specific antibody over time.

PMID- 8141594
TI  - Remembrance of experiments almost forgotten.

PMID- 8141595
TI  - "Chocolate addiction": a preliminary study of its description and its
      relationship to problem eating.
AB  - Definitions of chocolate addiction and its potential relationship to dieting and
      problem eating were investigated in 50 individuals who identified themselves as
      "chocoholics". Respondents were interviewed and completed a battery of
      questionnaires on food cravings, eating, weight, dieting and depression. On
      average this sample consumed about 12 (60-g) bars of chocolate per week and
      craved chocolate about six times per week. Cravings and amount consumed were not
      significantly related but amount consumed was significantly correlated with
      disinhibition (r = 0.3). Most (76%) respondents had definitions of chocolate
      addiction that centred on a lack of control around chocolate and regarded the
      "addictive" factor in chocolate as orosensory (i.e. taste, smell, texture).
      Unlike most others, dieters and secret eaters experienced negative affect
      following consumption of chocolate. Consumers who preferred to eat in secret
      reported a higher degree of aberrant eating. The extent to which the behaviour of
      "chocolate addicts" resembles that of eating disordered individuals and other
      addictions remains to be clarified.

PMID- 8141596
TI  - Pleasantness of a sweet taste during hunger and satiety: effects of gender and
      "sweet tooth".
AB  - Hungry or sated adult female (N = 29) and male subjects (N = 28), classified
      according to whether they had eaten or not within 2 h, rated four concentrations
      of sucrose in a lime drink for their sweetness intensity and pleasantness.
      Subjects also rated their attitude towards sweets in general (self-reported sweet
      tooth). Female subjects rated the solutions as less pleasant when tasted soon
      after a meal. Male subjects showed a non-significant trend in the same direction.
      Female subjects also rated the solutions as more intense than the male subjects
      did. Moreover, subjects who reported having a "sweet tooth" (regardless of
      gender) showed a significant alliesthesia effect (i.e., enhancement of
      pleasantness of sweet tastes by hunger), whereas those with "no sweet tooth" did
      not. We conclude that both gender and the degree of individual "sweet tooth"
      influence alliesthesia.

PMID- 8141597
TI  - Age-related changes in spontaneous food intake and hunger in humans.
AB  - Elderly people eat less than younger individuals. The nature of the changes in
      the meal pattern that occur with age were investigated by having 307 healthy
      adults, ages 20 to 80, maintain 7-day diaries of everything they ingested, the
      timing and conditions present, and subjective hunger, anxiety, depression, and
      activity. The lower intakes that occur with age were a consequence of the
      ingestion of smaller meals, eaten relatively slowly. The elderly were as
      responsive as younger subjects to a number of influences on intake, the time of
      day, the number of other people present, the subjective state of hunger, and the
      premeal contents of the stomach. These results suggest that the lower intakes in
      the elderly are a normal response to lower caloric expenditures. The state of
      hunger in the elderly affected intake equivalently to the young but intake did
      not affect hunger to the same extent as in younger subjects. This suggests that
      the internal state becomes less able to influence the subjective state as aging
      progresses and as a result the intake of the elderly may become primarily
      influenced by external factors.

PMID- 8141598
TI  - The effects of preloads varying in physical state and fat content on satiety and
      energy intake.
AB  - This study investigated the effect of the physical state and fat content of a
      preload on feelings of hunger and satiety and subsequent energy intake. Thirty
      three normal-weight female subjects each received nine different 550-ml preloads
      which were served as breakfast. The preloads differed in physical state and fat
      level. There were three types of physical state (liquid, solid with locust bean
      gum, and solid with gelatin) combined with three energy levels (0.42, 1.67, and
      3.35 MJ). The energy differences were due only to differences in fat content.
      Subjects were not allowed to eat or drink (except water) for 3.5 h after preload
      consumption. In this period they rated their feelings of appetite. Subjects
      recorded their voluntary food intake for the remainder of the study day and the
      day after the study day. There were no effects of the different amounts of fat or
      the three different physical states on energy intake during the remainder of the
      day or the day after. With respect to the appetite ratings, however, it appeared
      that the solid preloads were more satiating than the liquid preloads and the
      solid preloads were more satiating with fibre (locust bean gum) than without
      fibre (gelatin). The high-fat preloads were more satiating than the low-fat
      preloads.

PMID- 8141599
TI  - Meat: still the number one choice in Europe.

PMID- 8141600
TI  - Children's food purchase requests.

PMID- 8141601
TI  - Meal patterns of the elderly in rural Kentucky.

PMID- 8141602
TI  - Food choices in Czechoslovakia.

PMID- 8141604
TI  - Social science perspectives in nutrition.

PMID- 8141603
TI  - Molecular pathogenesis of obesity in the fatty rat.

PMID- 8141605
TI  - Oral experience and the control of ingestion: lessons from development studies.

PMID- 8141606
TI  - Stimulation of human scalp papilla cells by epithelial cells.
AB  - Evidence for the growth stimulatory properties of human keratinocyte-derived
      conditioned medium on human scalp dermal papilla cells and a mouse fibroblast
      cell line (Balb/c 3T3) is presented. There was no mitogenic effect on human
      keratinocytes. This conditioned medium induced a 2-5-fold increase in mitogenic
      activity in papilla cells relative to sham-conditioned medium as measured by 3H
      thymidine incorporation. The papilla cell growth-stimulating activity of the
      conditioned medium was sensitive to heat, and from size exclusion the molecular
      weight was greater than 3000 Da.

PMID- 8141607
TI  - Genetic analysis of ultraviolet radiation-induced skin hyperplasia and neoplasia
      in a laboratory marsupial model (Monodelphis domestica).
AB  - Monodelphis domestica, the laboratory opossum, develops hyperplasia and neoplasia
      of shaved skin after repeated exposure to ultraviolet radiation (UVR). We exposed
      Monodelphis from genetically diverse families within our colony to determine
      whether there are any heritable components to the risk of two distinct skin
      lesion phenotypes-melanocytic nevus (MN) and advanced hyperkeratosis (HK). From
      about 5 months of age, animals were shaved and exposed three times a week to a
      dose of about 125 J/m2 of UVR (spectral peak, 302 nm; range, 280-400 nm). Of 33
      sibships (151 individuals) that completed at least 30 weeks of the protocol, 137
      completed 45 weeks. For genetic analyses, each animal was classified at 30 and 45
      weeks as affected with MN and HK or not affected. Heritabilities were estimated
      using a variance decomposition approach. Susceptibility to MN showed no
      significant evidence for a genetic component at 30 or 45 weeks. In sharp
      contrast, susceptibility to HK was under virtually complete genetic control
      (heritability, 0.999; P < 0.001) at 30 weeks, and had a moderately high
      heritability (0.702; P < 0.001) at 45 weeks. We conclude that this model has
      great potential for identifying genes that confer susceptibility to UVR-induced
      skin lesions and for investigating environmental factors that may contribute to
      the increasing incidence of skin cancer in human populations.

PMID- 8141608
TI  - Normal oxidative activity and chemotaxis of circulating neutrophils in patients
      treated with photopheresis.
AB  - In photopheresis peripheral leukocytes are exposed to photoactivated 8
      methoxypsoralen in an extra-corporeal flow system. The present study was
      performed to characterize the effect of photopheresis upon the function of
      peripheral circulating neutrophils. Superoxide generating capacity and
      chemotactic ability of peripheral circulating neutrophils were tested in seven
      patients immediately before and after treatment with photopheresis. Superoxide
      generation stimulated by phorbol-12-myristate-13-acetate and N-formyl-methionyl
      leucyl-phenylalanine (fMLP) and fMLP-induced chemotaxis were found not to be
      influenced by photopheresis. We conclude that circulating neutrophils obtained
      from patients treated with photopheresis possess normal superoxide-generating
      capacity and chemotactic ability.

PMID- 8141609
TI  - Treatment of psoriasis with a new micronized 5-methoxypsoralen tablet and UVA
      radiation.
AB  - Since 1974, phototherapy with psoralen and ultraviolet A (UVA) has been used
      successfully for the treatment of psoriasis. However, undesirable side effects,
      including phototoxicity, nausea, stomach pain and headaches, have led
      investigators to develop new psoralen compounds. 5-Methoxypsoralen (5-MOP) has
      thus been introduced as an alternative to 8-MOP because of its less pronounced
      side effects. Since the absorption kinetics and bioactivity of 5-MOP are known to
      be variable, a new micronized tablet form (5-MOPm) has been developed. In an open
      randomized study, oral treatments with 5-MOP or 5-MOPm plus UVA radiation were
      compared in 22 psoriatic patients. Skin type and initial psoriasis area severity
      index did not differ significantly between treatment groups. Serum concentrations
      were significantly higher (320 vs 85.82 ng/ml) and occurred earlier (51.8 vs
      229.09 min) with 5-MOPm. In addition, a reduction in PASI of more than 90% was
      achieved sooner (10.63 vs 17.27 treatments) and with a lower cumulative UVA dose
      (145.89 vs 232.11 J/cm2), in the group treated with 5-MOPm. No side effects were
      observed with 5-MOPm. Our data indicate that 5-MOPm has a higher bioavailability,
      clinical efficacy and tolerability than the commonly used 5-MOP.

PMID- 8141610
TI  - Epidermolysis bullosa acquisita--successful treatment with colchicine.
AB  - The treatment of epidermolysis bullosa acquisita (EBA) is difficult and often
      disappointing. We report on the successful treatment of two EBA patients with
      colchicine. The drug was administered orally at an initial dose of 2 mg/day.
      After 2 weeks of therapy a dramatic improvement was observed. Most of the
      cutaneous and buccal mucosal lesions had healed and both of the patients were
      able to go about their normal daily activities. In the first patient the disease
      was refractory to dapsone alone or combined with steroids. In the second patient
      no other treatment was tried. After 6 months a maintenance dose of 1 mg/day
      colchicine was given. The disease had remained stable in both patients at the
      time of writing for more than 8 months. No side effects were observed. We suggest
      that colchicine may be a helpful and safe drug for patients with EBA.

PMID- 8141611
TI  - Stratum corneum lipid morphology and transepidermal water loss in normal skin and
      surfactant-induced scaly skin.
AB  - Stratum corneum lipid morphology was evaluated using attenuated total reflectance
      infrared spectroscopy (ATR-IR) in normal skin and surfactant-induced scaly skin
      to evaluate skin barrier function. To evaluate the degree of order of the
      intercellular lipid alkyl chain conformation, we measured the wavenumbers
      (frequency shifts) of the symmetrical and asymmetrical C-H stretching vibrations
      observed at approximately 2850 cm-1 and 2920 cm-1, respectively. There was a
      correlation between the wave-number and transepidermal water loss in normal skin.
      However, no difference was observed in surfactant-induced scaly skin from the
      baseline value in the wavenumbers of the C-H vibrations. These results suggest
      that in normal skin, lipid morphology plays an important role in the barrier
      function of the stratum corneum. However, the decline in barrier function in
      scaly skin is not due to conformational disorder of the lipid alkyl chain.

PMID- 8141612
TI  - Long-term follow-up study of changes in lipid peroxide levels and the activity of
      superoxide dismutase, catalase and glutathione peroxidase in mouse skin after
      acute and chronic UV irradiation.
AB  - Lipid peroxide levels, the activities of superoxide dismutase (SOD), catalase and
      glutathione peroxidase (GSH-Px), and the development of tanning in the skin of
      C57 BL/6 mice were assessed for long periods, from very early to late stages,
      after acute or chronic UVB irradiation. Acute UVB irradiation produced an
      increase in lipid peroxide levels that peaked 18 h after irradiation, after which
      the levels declined to a minimum 2-3 days after irradiation and then gradually
      rose to baseline. Chronic irradiation caused the lipid peroxide level to fall to
      a minimum at 0.5-1.0 weeks, after which it gradually returned to baseline by the
      third week. SOD and GSH-Px activities decreased sharply after acute irradiation,
      reaching a minimum 18 h after irradiation. Following chronic irradiation, these
      enzyme levels peaked after 0.5 weeks, and thereafter declined gradually to the
      original levels 3 weeks after irradiation. In contrast, catalase activity did not
      change significantly. Tanning began to increase at 1.5 weeks after irradiation,
      with an accelerated rate of increase from the third week.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8141613
TI  - In vivo targeting of integrin receptors in human skin xenografts by intravenously
      applied antibodies.
AB  - We examined whether systemically injected monoclonal antibodies (mAbs) directed
      to cell-surface glycoproteins of human keratinocytes reach their target antigens
      in xenograft transplants of normal human skin on SCID mice. The integrins alpha 6
      beta 4, expressed in the basal cell layer of human epidermis, and glycoprotein
      T16 (gp 40/50), expressed in terminally differentiating keratinocytes of the
      stratum spinosum, were selected as targets. It was found that all injected mAbs
      selectively localized to their antigens and bound and saturated their targets
      even in the uppermost layers of the stratum malpighii. This could easily be
      monitored by direct immunofluorescence staining since SCID mice lack endogenous
      production of significant amounts of immunoglobulins. After a single injection,
      mAbs could still be detected at the target site after 14 days. Our results proved
      that heterologous immunoglobulins pass systemic capillary filters in this
      xenograft model and specifically bind to their target molecules. Thus,
      xenografted SCID mice provide a versatile model for studying cell-surface
      glycoprotein-mediated interactions by the use of functionally interfering
      antibodies under in vivo conditions in human skin.

PMID- 8141614
TI  - Distribution of metallothionein in normal and pathological human skin.
AB  - The expression and distribution of metallothionein (MT) in frozen sections of
      normal and pathological human skin was studied using the monoclonal antibody L2E3
      directed against MT derived from human fetal liver. Immunohistochemical staining
      of normal fetal and adult skin revealed strong reactivity in basal keratinocytes
      of epidermis and outer hair root sheath, hair matrix cells and the secretory
      coil, but not the exocrine portion of eccrine glands; myoepithelial cells around
      apocrine sweat glands were similarly stained. In epidermal hyperplasia, variable
      numbers of suprabasal keratinocytes were stained, whereas in interface
      dermatitis, interrupted staining was found in the basal layer. Weak or scattered
      staining was observed in squamous tumours, whereas basal cell carcinomas did not
      show consistent staining. The distribution of MT in normal skin was in line with
      the germinative role of basal keratinocytes and hair matrix cells, whereas its
      distribution in hyperplastic epidermis was in line with experimental animal data,
      and reflected the increase in the germinative pool in these conditions. It is
      concluded that monoclonal antibody L2E3 may serve as a valuable
      immunohistochemical marker in diagnostic cutaneous pathology since it labels
      basal keratinocytes selectively, and since it discriminates between eccrine and
      apocrine sweat glands.

PMID- 8141615
TI  - The effect of cryo-treatment on epidermal Langerhans cells and immune function in
      mice.

PMID- 8141616
TI  - [The use of vagina and percutaneous surgery in stress urinary incontinence:
      description, foundations, and indications].
AB  - Our modifications to the Stamey, Guittes and Raz procedures are described and
      discussed. Our own experience of seven years and the experience reported by other
      authors in the world literature demonstrate the usefulness of the vagina in
      endoscopic percutaneous surgical treatment of female stress urinary incontinence.
      The complication rate is reduced, efficacy is enhanced and different alternatives
      are possible depending on the anatomic and functional characteristics of each
      case.

PMID- 8141617
TI  - [Primary amyloidosis in the bladder: diagnostic and therapeutic update].
AB  - We describe an additional case of primary amyloidosis of the bladder whose form
      of presentation warranted a differential diagnosis from carcinoma of the bladder.
      The diagnosis was made on the histological findings and the immunohistochemical
      analyses revealed amyloid fibrils that reacted against the light chain lambda
      antiserum. The treatment of choice was TUR, which resolves the condition in most
      of the cases. Conservative surgery, however, does not prevent new deposits and
      undetected residual lesions may persist, which may warrant other complementary
      procedures in these patients. After the diagnosis has been made, it is important
      to discard systemic amyloidosis.

PMID- 8141618
TI  - [Testicular tumors in acquired immunodeficiency syndrome].
AB  - Apart from infections, tumors are one of the manifestations of AIDS. Kaposi's
      sarcoma of the penis or scrotum is the most common urological tumor in patients
      with AIDS. Renal tumors and, to date, 56 testicular tumors have also been
      described. It remains unclear whether immunodeficiency is a decisive factor in
      the appearance of testicular tumors. However, these tumors present in the
      advanced stages, which is probably ascribable to changes in cellular immunity.
      Treatment is not unlike that of conventional therapy, the response being similar
      to that of patients without AIDS. We describe a case of germ cell carcinoma which
      manifested as multiple pulmonary metastases in a 26-year-old patient with AIDS.

PMID- 8141619
TI  - [Perineal radical prostatectomy in the age of laparoscopy].
AB  - With the advent of laparoscopic lymphadenectomy, attention has been focussed
      again to the perineal approach for cancer of the prostate. The high rate of
      postoperative impotence and the abdominal incision required had made radical
      perineal prostatectomy unpopular. From August 1990 to July 1991, 76 patients with
      localized prostate cancer were surgically treated at the University of St. Louis.
      These patients were divided into three groups; group A comprised 26 patients who
      were submitted to laparoscopic lymphadenectomy and radical perineal
      prostatectomy, group B comprised patients treated by laparoscopic lymphadenectomy
      and radical retropubic prostatectomy, and group C or controls underwent open
      lymphadenectomy and radical retropubic prostatectomy. Fifty-three patients were
      sexually potent preoperatively but only 20 (7 from group A, 5 from group B and 8
      from group C) were considered for preservation of the neurovascular bands. All
      the patients were followed for a minimum of one year. Comparison of these three
      groups revealed significant differences for perioperative bleeding and
      postoperative hospital stay in favor of Group A. The overall stress incontinence
      rate was 5.3% and the complications ranged from 4.1% for group C and 29.1% for
      group B. The postoperative sexual potency ranged from 57% for group A to 75% for
      group C, the differences not being statistically significant. Radical perineal
      prostatectomy is as valid as radical retropubic prostatectomy for localized
      prostatic cancer and has the advantages of less bleeding and a faster recovery,
      particularly if combined with laparoscopic lymphadenectomy.

PMID- 8141620
TI  - [Urologic complications in renal transplantation. Our experience with 700 cases].
AB  - The present study reports on the urological complications observed in 700 kidney
      transplants performed from February, 1975 to January, 1993. The techniques used
      for reconstruction of the urinary tract have been extravesical and intravesical
      ureteroneocystostomy. In some cases other different techniques have been used.
      Urinary extravasation, ureteric obstruction and lymphoceles were the most
      frequent complications. Urinary leakage was observed in 5.7% and was resolved by
      different surgical techniques, but generally by open surgery. Ureteric
      obstruction has been a very uncommon complication resolved by conservative
      treatment or open surgery. Twenty-six lymphoceles were diagnosed. We advocate the
      use of both open surgery and percutaneous techniques for the management of
      urological complications secondary to renal transplantation.

PMID- 8141621
TI  - [Urodynamic findings in Shy-Drager syndrome].
AB  - The neuronal degeneration in specific areas of the brain and cord implicated in
      the micturition reflexes that present in Shy-Drager syndrome lead to
      vesicourethral dysfunction in these patients. Because it is unspecific,
      urodynamic studies are required for correct diagnosis. We report on three
      patients with this syndrome and compare our findings with those reported to date.
      The urological complications of this disorder and the different treatments are
      discussed.

PMID- 8141622
TI  - [Penile erection using vacuum devices: our experience with 100 impotent patients
      with organic etiology].
AB  - The aim of this study was to determine the efficacy and acceptability of the
      erection suction device in patients with erectile dysfunction from organic
      causes. One hundred patients suffering from impotence due to different organic
      etiologies were evaluated following a protocol which included patient history,
      physical examination, general blood tests, hormonal tests, erection (Rigiscan)
      study and vascular and neurological tests. In 87% of the patients, a correct
      erection was achieved when the suction device was used for sexual intercourse.
      However, only 28.7% accepted to use this method routinely.

PMID- 8141623
TI  - [Intravesical foreign body. Post-traumatic migration of autologous bone
      fragment].
AB  - We report on a 24-year-old female patient with posttraumatic migration of a bony
      fragment from the site of the fracture to the bladder. The foreign body was
      removed from the bladder by endoscopy. The etiopathogenic mechanism, clinical
      signs, diagnostic method and therapeutic management are discussed.

PMID- 8141624
TI  - [Schistosomiasis (bilharziosis). Importance of cytology. Report of 2 cases].
AB  - We report two cases of bilharziasis of the bladder in immigrants who presented
      with spontaneous hematuria. This condition was diagnosed by urine cytology. The
      current tide of immigration and tourism have led to an increased number of
      diseases acquired abroad. A simple, economic and rapid method for diagnosing
      schistosomiasis in patients at risk with hematuria is described.

PMID- 8141625
TI  - [Transitional carcinoma of the prostate. Report of a case treated with
      chemotherapy].
AB  - A case of transitional cell carcinoma of the prostate is described which had been
      diagnosed following TUR of the prostate due to cervico-prostatic obstruction.
      Subsequent cystoscopic and cytological controls, as well as multiple bladder
      biopsies have discarded a concomitant urothelial tumor. We underscore the rarity
      of transitional cell tumor of the prostate, its response to chemotherapy and the
      possibility of suspecting this tumor type when there is massive invasion of the
      prostate following TUR.

PMID- 8141626
TI  - [Male pseudohermaphroditism: perineoscrotal pseudovaginal hypospadias].
AB  - We report on a case of pseudovaginal perineoscrotal hypospadias. The gross and
      microscopic features of this condition are described. The existence of ambiguous
      external genitalia without gynecomastia together with a complete inhibition of
      the mullerian structures is confirmed.

PMID- 8141627
TI  - [Giant urethral lithiasis].
AB  - We report on a 46-year-old male with a giant calculus of the anterior urethra.
      The etiopathogenesis, diagnosis and treatment of this condition are discussed.
      Similar features have been described in one case of giant intradiverticular
      calculus reported in the literature.

PMID- 8141628
TI  - [Changes in deposition pattern as presentation form of uretero-intestinal
      endometriosis].
AB  - A case of ureteric and colonic obstruction secondary to endometriosis is
      described. We briefly review its pathogenesis and discuss the urologic and bowel
      implications, symptoms and signs, diagnosis and treatment. Because it is usually
      silent, urographic evaluation is advisable in all cases of endometriosis.
      Treatment is by surgery and adjuvant hormone therapy is given preoperatively or
      postoperatively for residual disease.

PMID- 8141629
TI  - [Hypernephroma in horseshoe kidney].
AB  - The case in discussion is that of a 38-year-old patient with a history of
      artralgia, anemia and a general syndrome. The physical examination revealed a
      tumor in the right hypochondrium and the right flank and she was admitted to the
      hospital due to the rapid growth of the tumor. On operating we found a horseshoe
      kidney and a hypernephroma in the isthmus of the kidney. Emphasis is made in
      performing a detailed radiological study in order to determine the best possible
      surgical approach.

PMID- 8141630
TI  - Endourological management of benign renal cyst: a simplified procedure.
AB  - A simple endourological management of benign renal cyst is described.
      Percutaneous circular electrosection of the peripheric cyst wall is performed,
      thereafter the cyst wall is extracted en bloc and an aspirative drainage is
      placed for 2 days. Five patients with symptomatic renal cyst were treated with
      this method. No major complications have been observed. All patients are
      asymptomatic at follow-up and only one patient has residual cyst.

PMID- 8141631
TI  - President's message: Diabetes Control and Complications Trial (DCCT):
      implications for the ESRD population. Interview by Terran Warren Sims.

PMID- 8141632
TI  - Rhabdomyolysis: a comprehensive guide.
AB  - Rhabdomyolysis is a clinical syndrome that results from the release of skeletal
      muscle cell contents, specifically myoglobin, into the plasma. While the precise
      pathogenesis of rhabdomyolysis is not clearly understood, rhabdomyolysis has been
      implicated as a major cause of acute renal failure. This article will serve as a
      comprehensive guide for nephrology nurses. A partial review of the literature,
      pathophysiology/etiologic factors, diagnosis, clinical presentation, and nursing
      interventions/treatment will be provided.

PMID- 8141633
TI  - Gaming: a creative strategy for staff education.
AB  - Providing staff development in a stimulating, innovative manner is the challenge
      of all nurse educators. This article discusses gaming, a creative teaching
      strategy that can help meet these needs. Games designed specifically for the
      education of dialysis staff will be reviewed. Advantages of the various games
      will also be examined.

PMID- 8141634
TI  - Posterior urethral valves: pathophysiology and clinical implications.
AB  - Posterior urethral valves are a congenital defect affecting the prostatic
      urethra. They may be the most common cause of obstructive uropathy leading to
      childhood renal failure. Patients exhibit a broad spectrum of symptomatology and
      pathology that are determined by the degree and duration of obstruction, the
      presence or absence of urinary infection, and the extent of renal dysplasia. With
      early detection and proper treatment, which may include renal transplantation,
      the outlook for these children has improved significantly.

PMID- 8141635
TI  - Evaluation of a hemodialysis patient education and support program.
AB  - This study examined the effects of a hemodialysis educational and support program
      (HESP) on patients' physical and psychosocial adaptations to end stage renal
      disease. The study employed a pretest/posttest modified Solomon experimental
      design with control group. Data were collected at 3-month intervals following the
      educational intervention. Results of the study indicated that nurses can have an
      impact on the patient learning experience by providing support and one-to-one
      teaching sessions, and actively involving patients in their own care.
      Additionally, nurses can facilitate active patient learning through enhanced
      teaching methods.

PMID- 8141636
TI  - Stress inoculation education and counseling with patients on hemodialysis.
AB  - A single-subject experimental design with multiple, repeated measures was used to
      investigate the effects of the cognitive-behavioral intervention of stress
      inoculation education (SIE) and counseling on anxiety, depression, psychosocial
      adjustment to illness, and perception of hemodialysis stressors. Two intervening
      variables, interpersonal support and control, were assessed to determine their
      influence on the dependent variables. The analyzed data suggested that SIE and
      counseling were effective in decreasing some problems for all study patients.

PMID- 8141637
TI  - Case study of the anemic patient: epoetin alfa--focus on inflammation.
AB  - Infection and inflammation are common problems in patients with end-stage renal
      disease. Both conditions can interfere with normal erythropoiesis and lead to a
      worsening of anemia and a suboptimal response to Epoetin alfa therapy. By
      understanding the pathophysiologic effects of infection and inflammation,
      assessing the patient's clinical status, and analyzing relevant laboratory
      values, nurses can intervene early and minimize the impact of these conditions on
      hematocrit.

PMID- 8141638
TI  - Challenges of caring for a hemophiliac patient with HIV nephropathy.
AB  - Throughout his life, J.G. sought control over his hemophilia, often putting
      himself at risk by playing sports and trying to live as normal a life as
      possible. He actively directed his life and decided what risks were worth taking
      and in the end, he directed his death. Outcome goals originally formulated in
      J.G.'s plan of care were met. Active bleeding was controlled. The vascular access
      was free of complications and in the end was used as the only way to administered
      medications to provide comfort. Was the decision to dialyze worth it? The answer
      varies from hostility at the effort and valuable resources used, to apathy, to
      collective support for complying with the patient's informed decision. As nurses
      we actively participated in a plan of care to keep him alive, and altered our
      plan when the decision was made to withdraw treatment. A sense of sadness
      remains, but also a sense of closure without guilt, frustration, or remorse for
      having had the chance to participate. It was worth it for J.G. and his wife.

PMID- 8141640
TI  - Reuse of PD cycler tubing.

PMID- 8141639
TI  - OKT 3 reaction in a renal transplant patient.
AB  - In this case, the intended patient outcomes were achieved. Nursing was clearly
      able to take a very proactive role in providing the necessary emergency patient
      care to prevent further patient compromise. Once the immediate physiologic danger
      of respiratory decompensation was treated, nursing moved on to intervene in the
      less-serious complications associated with OKT 3 reaction to assure maximal
      patient comfort. Finally, patient teaching was done both to assess the learning
      needs associated with the OKT 3 reaction, as well as to prepare the patient and
      family for administration of additional doses of OKT 3. These nursing actions
      resulted in a very favorable outcome for both the patient and family.

PMID- 8141641
TI  - Recombinant human growth hormone.
AB  - Recombinant human growth hormone was initially used as replacement therapy in
      children with short stature. As rhGH has become more readily available, it has
      been tested in a variety of other individuals who have delayed growth. Children
      with ESRD experience significant problems with delayed growth, thus replacement
      therapy with rhGH has been used in this population. resulting in improved growth
      velocity. The clinical significance of improved height may have a positive impact
      on the psychological well being of these children.

PMID- 8141642
TI  - Eligibility requirements for certification examination reflect our commitment to
      quality care.

PMID- 8141643
TI  - Evidence that phenol phosphorylation to phenylphosphate is the first step in
      anaerobic phenol metabolism in a denitrifying Pseudomonas sp.
AB  - Anaerobic phenol degradation has been shown to proceed via carboxylation of
      phenol to 4-hydroxybenzoate. However, in vitro the carboxylating enzyme was
      inactive with phenol; only phenylphosphate (phosphoric acid monophenyl ester) was
      readily carboxylated. We demonstrate in a denitrifying Pseudomonas strain that
      phenylphosphate is the first detectable product formed from phenol in whole cells
      and that subsequent phenylphosphate consumption parallels 4-hydroxybenzoate
      formation. These kinetics are consistent with phosphorylation being the first
      step in anaerobic phenol degradation. Various cosubstrates failed so far to act
      as phosphoryl donor for net phosphorylation of phenol in cell extracts. Yet,
      cells anaerobically grown with phenol contained an enzyme that catalyzed an
      isotope exchange between [U-14C]phenol and phenylphosphate. This
      transphosphorylation activity was anaerobically induced by phenol but was stable
      under aerobic conditions and required Mn2+ and polyethylene glycol. Activity was
      optimal at pH 5.5 and half-maximal with 0.6 mM Mn2+, 0.2 mM phenylphosphate, and
      1 mM phenol. It is proposed that the phenol exchange/transphosphorylation
      reaction is catalyzed as partial reaction by an inducible phenol phosphorylating
      enzyme. The isotope exchange demands that a phosphorylated enzyme was formed in
      the course of the reaction, which might be similar to the phosphotransferase
      system of sugar transport.

PMID- 8141644
TI  - The extracellular nuclease of Serratia marcescens: studies on the activity in
      vitro and effect on transforming DNA in a groundwater aquifer microcosm.
AB  - A quantitative endonuclease assay, which relies on the introduction of single and
      double strand breaks into supercoiled plasmid DNA, was used to study the activity
      of the extracellular nuclease of Serratia marcescens SM6 in buffer and in
      groundwater. The parallel enzyme concentration-dependent production of relaxed
      and linear plasmid molecules suggests that the nuclease produces single and
      double strand breaks in duplex DNA. Bovine serum albumin stimulated the nuclease
      activity towards DNA and RNA and increased the stability of the enzyme against
      thermal inactivation. The DNase activity at 4 degrees C and 50 degrees C was
      almost half of that at the optimum temperature (37 degrees C). The nuclease was
      active in groundwater, although the specific activity was lower than in buffer.
      In a groundwater aquifer microcosm, mineral-adsorbed transforming DNA was
      substantially less accessible to the nuclease than was dissolved DNA. The data
      suggest that the extracellular nuclease of Serratia marcescens may contribute to
      DNA turnover in the environment and that adsorption of DNA to minerals provides
      protection against the nuclease.

PMID- 8141645
TI  - Effects of beraprost sodium, a stable analogue of prostacyclin, on hyperplasia,
      hypertrophy and glycosaminoglycan synthesis of rat aortic smooth muscle cells.
AB  - The effects of beraprost sodium, a stable analogue of prostacyclin, on the
      syntheses of DNA, protein and glycosaminoglycans (GAG) of cultured vascular
      smooth muscle cells (SMC) were studied. SMC were isolated from the thoracic aorta
      of male Wistar rats. The syntheses of DNA, protein and GAG of SMC were determined
      by incorporations of [3H]thymidine, [3H]leucine and [35S]sulfuric acid,
      respectively. Insulin at a concentration of 10(-6) M stimulated DNA synthesis 4
      fold compared to control. Beraprost sodium suppressed the insulin-stimulated DNA
      synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed
      it by 68% at 10(-5) M. Platelet derived growth factor (PDGF) at a concentration
      of 20 ng/ml stimulated DNA synthesis 6 fold compared to control. Beraprost sodium
      suppressed the PDGF-stimulated DNA synthesis dose-dependently at concentrations
      greater than 10(-7) M and suppressed it by 51% at 10(-5) M. Beraprost sodium
      suppressed GAG synthesis dose-dependently at concentrations greater than 10(-7) M
      and suppressed it by 49% at 10(-5) M. However, beraprost sodium at concentrations
      up to 10(-5) M did not affect protein synthesis. These results indicate that
      beraprost sodium suppressed the proliferation and GAG synthesis of SMC but did
      not affect hypertrophy. Beraprost sodium may be a potent antiarteriosclerotic
      agent through suppression of hyperplasia of SMC and modification of matrix
      protein.

PMID- 8141646
TI  - Effects of dexamethasone on migration of human monocytes in response to oxidized
      beta-very low density lipoprotein.
AB  - OBJECTIVE: We previously showed that dexamethasone inhibited the development of
      atherosclerosis in cholesterol-fed rabbits. In the present study, we investigated
      the mechanisms of this inhibition. METHODS: Monocytes were isolated from the
      peripheral blood of healthy donors. Cell suspensions were incubated with
      dexamethasone, 10(-11)-10(-4)M, for 90 minutes at 37 degrees C. Rabbit beta-very
      low density lipoprotein(beta-VLDL) was obtained from New Zealand White rabbits
      that had been fed chow containing 1% cholesterol. Oxidative modification of beta
      VLDL was performed by auto-oxidation. We measured the migration of monocytes in
      response to native and oxidized beta-VLDL using a 48-well microchemotaxis
      chamber. RESULTS: Oxidized beta-VLDL stimulated the migration of monocytes dose
      dependently in the range between 0.5 and 2 nmol/mg protein. Dexamethasone
      inhibited the chemotaxis of monocytes exposed to oxidized beta-VLDL in a dose
      dependent manner more than 10(-9)M. CONCLUSIONS: Inhibition of the chemotactic
      response of monocytes exposed to oxidized beta-VLDL may be a mechanism for the
      anti-atherogenic effect of dexamethasone in cholesterol-fed rabbits.

PMID- 8141647
TI  - Enhanced degradation of high density lipoprotein by peritoneal macrophages from
      nude mice is attenuated by interleukin-1.
AB  - Athymic nude mice are characterized by deficient cellular immunity due to almost
      complete absence of functional mature T-lymphocytes. Plasma HDL (the major
      cholesterol carrier in mice) cholesterol levels in nude mice were found to be
      reduced by 1.7 fold in comparison to control Balb/c mice. Cellular degradation of
      HDL by peritoneal macrophages (MPM) that were obtained from nude mice, was 2.5
      fold greater in comparison to MPM obtained from Balb/c mice. Since nude mice lack
      cytokines that can affect lipid metabolism, intravenous administration of 10
      micrograms/100g body weight of interleukin-1 (IL-1), tumor necrosis factor (TNF),
      or transforming growth factor (TGF) on HDL degradation by their PM, were
      investigated. IL-1 (but not TNF) reduced HDL (50 micrograms of protein/ml)
      cellular degradation from 810 +/- 34 to 350 +/- 12 ng/mg cell protein (p < 0.01)
      in nude mice. In control Balb/c mice, however, IL-1 as well as TNF enhanced
      macrophage degradation of HDL by 56% and 280%, respectively. TGF injection into
      nude mice (but not control mice) decreased HDL degradation by their MPM by 50%.
      We, thus, suggest that in nude mice the reduced plasma and HDL cholesterol levels
      are probably due to increased HDL degradation, which may be secondary to IL-1 and
      TGF deficiency.

PMID- 8141648
TI  - Terbutaline-induced desensitization in rabbit aorta in vitro.
AB  - In vivo administration of terbutaline, a beta 2-adrenergic agonist, desensitizes
      beta-adrenergic agonist-induced responses in isolated rabbit aorta.
      Characteristics of the desensitization following in vitro application of
      terbutaline and prevention of such desensitization by certain agents were
      studied. Endothelium-denuded rabbit aorta rings were incubated with 10 or 50
      microM terbutaline for 30 or 60 min, or with no drug as a control. Following
      contraction with 1 microM phenylephrine, relaxations to cumulative concentrations
      of isoproterenol were determined. Rings exposed to terbutaline relaxed less to
      isoproterenol, indicating desensitization of beta-adrenergic receptors. The
      desensitization was homologous, exposure time- and concentration-dependent, and
      at least partially reversible. It does not require extracellular calcium to
      develop and is not blocked by verapamil, ketotifen, prednisolone or nedocromil.
      Thus, terbutaline-induced desensitization occurs in vitro, is homologous, does
      not require calcium, and is not blocked by the four compounds tested.

PMID- 8141649
TI  - Baylor contributions to artificial organs.

PMID- 8141650
TI  - The status of pacemaker implantations in Japan.
AB  - It has been over 40 years since the initial clinical application of a cardiac
      pacemaker. Currently, approximately 300 per million patients in the United States
      and Europe are kept alive owing to the benefit of implantable pacemakers.
      Recently, the Japanese Cardiac Pacing Society and the Japanese Society of
      Artificial Organs performed pacemaker registry studies for 1989 and 1990. In this
      paper, results of this survey are described. Currently, implantable cardiac
      pacemakers are utilized only on the level of 120 per million patients in Japan.
      Surprisingly, all implantations were performed using foreign manufactured
      pacemakers. Despite the high level of electronic technologies available in Japan,
      no Japanese-made implantable cardiac pacemakers are utilized in Japan. One could
      speculate that a major reason for the low level of clinical application of
      cardiac pacemakers is that these devices are quite expensive because of the
      import duties imposed on them. It is necessary and strongly recommended that
      implantable cardiac pacemakers be manufactured in Japan in order for them to be
      utilized as fully as they are in the United States and Europe.

PMID- 8141651
TI  - Organ replacement therapy.

PMID- 8141652
TI  - Cardiopulmonary bypass with Nikkiso and BioMedicus centrifugal pumps.
AB  - In our department, a new compact and atraumatic centrifugal pump, Nikkiso, was
      developed as a second-generation cardiopulmonary bypass pump. To assess and
      confirm the function and controllability of this pump, comparative studies of
      cardiopulmonary bypass with Nikkiso and BioMedicus centrifugal pumps were
      performed using calves. Both pumps provided pump flows of 60-70 ml/kg/min without
      incidence. The hemodynamics of both groups were stable and within the normal
      range, and no leakage or thrombus formations were observed in either pump. All
      hematology and biochemistry data showed no significant differences between the
      two groups. Plasma free hemoglobin values of the Nikkiso pump tended to be lower
      than those of the BioMedicus pump. The Nikkiso pump was easy to handle because of
      its smaller size, and air removal was easily performed because of its low priming
      volume. The Nikkiso pump demonstrated easy manipulation and good controllability.
      This compact, atraumatic centrifugal pump meets the requirements for a second
      generation cardiopulmonary bypass pump.

PMID- 8141653
TI  - An ultimate, compact, seal-less centrifugal ventricular assist device: Baylor C
      Gyro pump.
AB  - We have developed a compact, seal-less, all-purpose centrifugal pump, the Baylor
      C-Gyro pump, which is intended as a long-term ventricular assist device (VAD) as
      well as a cardiopulmonary bypass pump. In attaining this goal, we began with
      eliminating the shaft seals by adopting a pivot bearing system at the impeller
      shaft. In addition, a ring magnet encased in the bottom of the impeller was
      coupled magnetically to a driver magnet placed outside the pump housing (C1
      Prototype). This first model yielded satisfactory performance in vitro with a
      flow rate of 8 L/min against 250 mm Hg at 2,400 rpm, and an index of hemolysis
      (IH) of 0.0083 g/100 L using bovine blood. In the second model, the C1 Eccentric
      Inlet Port Model, the inlet bearing support bar in the prototype were eliminated
      without reducing the prototype's performance. These designs for
      antithrombogenicity are being tested by the first in vivo experiment, which has
      lasted for more than 2 weeks.

PMID- 8141654
TI  - Internal hydraulic loss in a seal-less centrifugal Gyro pump.
AB  - A new index "loss factor Z" defined by Eq. 1 was introduced as the absolute
      expression of the mock loop resistance for testing a nonpulsatile pump. [formula:
      see text] where gamma is specific gravity of the fluid, g is the acceleration of
      gravity, delta P is total pressure head, and Q is flow. Z is expected to be
      constant, regardless of the pumping parameters. Z values obtained in the same
      mock loop but with different rotary blood pumps were almost identical and were
      defined as Z0. New methods of analysis of the flow-restrictive conditions of
      various rotary blood pumps are proposed in this paper: namely, differential loss
      factor delta Z, and loss factor sensitivity delta Z/delta A. The proposed Z-Q
      curves demonstrated better performance mapping than the conventional delta P-Q
      curves. Delta Z is the difference between the Z-Q curves of two different pumps.
      A is a design parameter of the pump; therefore delta Z/delta A is a quantitative
      expression of the effect of the design change on the hydraulic performance. These
      various indices were used to analyze the internal hydraulic loss of a centrifugal
      pump (Gyro pump). The relationship between its gap size (rotor casing) and
      hydraulic performance was assessed quantitatively by these indices. In this
      paper, the derivation processes and above-mentioned indices are described.

PMID- 8141655
TI  - Development of the Baylor/NASA axial flow ventricular assist device: in vitro
      performance and systematic hemolysis test results.
AB  - Our newly developed axial flow pump consists of a flow tube, an internal rotating
      impeller, and a fixed flow stator (we call the stator) behind the impeller. This
      pump produces a flow of 3 to 8 L/min against 50 to 150 mm Hg pressure difference,
      respectively, in the range of 10,000 to 16,000 rpm. An axial flow pump that will
      be used as a ventricular assist device (VAD) has to have low hemolytic and good
      antithrombogenic characteristics. This paper will show how to decrease the
      hemolytic properties of this axial flow pump systematically using a test matrix.
      The test variables evaluated were impeller blade tip geometry, impeller flow tube
      clearance (radial clearance), impeller stator clearance (axial clearance),
      impeller blade number, stator blade number, and impeller length. All in vitro
      hemolysis tests were performed at 5.0 L/min against 100 mm Hg pressure difference
      using a total of 83 bags of fresh bovine blood. The results were as follows: the
      impeller blade tip geometry did not significantly effect hemolysis, a 0.005-inch
      and a 0.009-inch radial clearance were significantly (p < 0.01 or 0.001) less
      hemolytic than the other clearances, a 0.075-inch axial clearance was
      significantly (p < 0.05) more hemolytic than the other clearances, two- and six
      bladed impellers were significantly (p < 0.01 and 0.02, respectively) less
      hemolytic than a four-bladed impeller, a five-bladed stator was significantly (p
      < 0.05 or 0.01) less hemolytic than the other stators, and the impeller length
      did not make a significant difference. Currently, the best index of hemolysis is
      0.031 +/- 0.018 g/100 L, and using parameters from these results, implantable
      devices are being fabricated.

PMID- 8141656
TI  - Kolff's heritage renewed.

PMID- 8141657
TI  - Axial flow ventricular assist device: system performance considerations.
AB  - A cooperative effort between Baylor College of Medicine and NASA/Johnson Space
      Center is under way to develop an implantable left ventricular assist device for
      either pulmonary or systemic circulatory support for more than 3 months'
      duration. Using methodical evaluation and testing, an implantable axial pump has
      been systematically improved. These improvements include the addition of an
      inducer as a pumping element in front of the impeller and the construction of an
      efficient brushless direct current motor. To date, less than 10 W of power is
      required to generate 5 L/min flow against 100 mm Hg. An index of hemolysis of
      0.021 g/100 L has been achieved. Two-day in vivo feasibility studies in calves
      are under way to evaluate the antithrombogenic nature of the pump. Further
      improvements in system efficiency, hemolytic performance, and the
      antithrombogenic nature of the pump are expected with the use of empirical
      studies, computer flow modeling, and in vivo testing in calves.

PMID- 8141658
TI  - Successful thermal management of a totally implantable ventricular assist system.
AB  - Thermal management of the implantable ventricular assist system (VAS) is
      important not only from the pathophysiological point of view but also from the
      standpoint of system endurance. The heat distribution within the Baylor VAS was
      measured using different motor housing materials and environmental conditions.
      The temperature of the circulating water in the mock loop was set at 37 degrees
      and 42 degrees C. A polycarbonate motor housing was not a suitable material
      because of the high temperature development in the actuation system. An anodized
      aluminum housing demonstrated excellent heat conductivity. The surface
      temperature of this motor housing was 41.6 degrees C when immersed in circulating
      water at 42 degrees C. Heat conduction from the motor to the circulating blood
      revealed an effective thermal path. In the worst case, the heat flux of the motor
      to the circulating blood revealed an effective thermal path. In the worst case,
      the heat flux of the motor housing was calculated to be less than 0.062 W/cm2--an
      acceptable level for the surrounding tissues.

PMID- 8141659
TI  - In vitro and in vivo validation tests for total artificial heart.
AB  - Properly planned in vitro and in vivo studies are mandatory to validate blood
      pump performance. However, standard procedures for in vitro and in vivo tests of
      total artificial heart (TAH) performance still do not exist. At Baylor College of
      Medicine, standard tests procedures for performance validation of the totally
      implantable TAH have been established. In this paper, these in vitro tests
      protocols (performance mapping tests, accelerated endurance test, hemolysis test,
      flow visualization tests, etc.) are described as well as in vivo test procedures
      (TAH implantation procedure, including surgical technique, postoperative
      management and tests, etc.). In addition, pathological protocols are presented.
      In our experience, these procedures are very simple, easy to perform, and
      inexpensive. These protocols are proposed as standard in vitro and in vivo tests
      for a TAH.

PMID- 8141660
TI  - The need for standardizing the index of hemolysis.
AB  - Hemolysis is one of the most important performance parameters of blood pumps.
      However, comparative in vitro evaluation of the reported hemolysis effect is
      difficult owing to the lack of uniformity in the test methods used. Currently,
      three types of formulas are generally accepted and widely used for the index of
      hemolysis: the traditionally used index of hemolysis (defined as grams of plasma
      free hemoglobin released per 100 L of blood pumped); the normalized index of
      hemolysis (normalized by hematocrit); and the modified index of hemolysis (taking
      into account not only hematocrit but also hemoglobin). In addition, the tested
      blood conditions are often not indicated in the reports. To address this
      confusing situation, all three indices of hemolysis were routinely derived in our
      laboratory. To avoid further confusion, the tested blood conditions and test loop
      were defined in each study in our laboratory. If we limit the acceptable range of
      hemoglobin in human blood, the normalized index of hemolysis is sufficient.
      Furthermore, using milligrams as the unit of expression would be easier and
      reasonable for comparing the less hemolytic blood pumps, such as the centrifugal
      pumps that are currently available clinically. We would like to propose this
      value of a normalized index of hemolysis in milligrams as the most useful formula
      for the index of hemolysis in the assessment of various types of rotary blood
      pumps.

PMID- 8141661
TI  - Flow visualization in the Baylor total artificial heart.
AB  - To analyze the flow patterns of the left and right blood chambers of the total
      artificial heart (TAH), flow visualization studies were performed. Two setup
      levels were used for the flow visualization studies. For estimating the global
      flow patterns, the pumps were illuminated using incandescent light, and the
      patterns were recorded by either videotape or photography. To evaluate sectional
      flow patterns, a laser light was applied, and the pump could be scanned
      segmentally. The flow patterns were recorded by a high-speed camera. A signal was
      also used that synchronized the timing of the camera shutter to the pusher-plate
      movement signal. In the left pump chamber, major stagnations were observed in the
      middle area of the inflow site. To solve this problem, a modification was made
      that changed the inflow direction appropriately. After evaluation of the inflow
      port direction, a proper flow pattern was obtained, which was validated by a
      global flow visualization study. Furthermore, both pump chambers indicated
      excellent flow patterns as obtained by a segmental flow visualization study
      method utilizing a laser light. The Baylor TAH demonstrated excellent flow
      patterns in flow visualization studies, with antithrombogenicity expected. These
      flow visualization studies are very useful not only for validations of global
      flow patterns but also for validations of local areas of stagnation in various
      blood pumps.

PMID- 8141662
TI  - Totally implantable total artificial heart and ventricular assist device with
      multipurpose miniature electromechanical energy system.
AB  - A multipurpose miniature electromechanical energy system has been developed to
      yield a compact, efficient, durable, and biocompatible total artificial heart
      (TAH) and ventricular assist device (VAD). Associated controller-driver
      electronics were recently miniaturized and converted into hybrid circuits. The
      hybrid controller consists of a microprocessor and controller, motor driver, Hall
      sensor, and commutation circuit hybrids. The sizing study demonstrated that all
      these components can be incorporated in the pumping unit of the TAH and VAD,
      particularly in the centerpiece of the TAH and the motor housing of the VAD. Both
      TAH and VAD pumping units will start when their power line is connected to either
      the internal power pack or the external battery unit. As a redundant driving and
      diagnostic port, an emergency port was newly added and will be placed in
      subcutaneous location. In case of system failure, the skin will be cut down, and
      an external motor drive or a pneumatic driver will be connected to this port to
      run the TAH. This will minimize the circulatory arrest time. Overall efficiency
      of the TAH without the transcutaneous energy transmission system was 14-18% to
      deliver pump outputs of 4-9 L/min against the right and left afterload pressures
      of 25 and 100 mm Hg. The internal power requirement ranged from 6 to 13 W. The
      rechargeable batteries such as NiCd or NiMH with 1 AH capacity can run the TAH
      for 30-45 min. The external power requirement, when TETS efficiency of 75% was
      assumed, ranged from 8 to 18 W. The accelerated endurance test in the 42 degrees
      C saline bath demonstrated stable performance over 4 months. Long-term endurance
      and chronic animal studies will continue toward a system with 5 years durability
      by the year 2000.

PMID- 8141663
TI  - Assessment of currently available low-density lipoprotein apheresis systems.
AB  - It has already been 10 years since the introduction of low-density lipoprotein
      (LDL) apheresis technologies. They have been established as technically and
      medically feasible for long-term treatment and economically acceptable, and their
      long-term treatment effects have been determined. Currently, there are efforts to
      develop more selective LDL removal systems. However, after 10 years of research,
      it is time to carefully review this strategy. The approach may have become too
      specific in light of the multiple macromolecules involved in the pathogenesis of
      atherosclerosis. In this paper, the six currently available LDL apheresis systems
      (plasma exchange, double filtration plasmapheresis, thermofiltration, LDL
      chemical adsorption (Kaneka system), LDL immunoadsorption, and the heparin
      induced extracorporeal LDL precipitation [HELP] system) were reviewed and scored
      from various points of view such as effectiveness, simplicity, safety, and cost
      performance. Finally, each system was assessed from the global point of view in
      relation to the pathogenesis of lipid-related diseases.

PMID- 8141664
TI  - Enameloid formation in two tetraodontiform fish species with high and low
      fluoride contents in enameloid.
AB  - Forming teeth of parrotfish and pufferfish were viewed by transmission electron
      microscopy to correlate cytological features of the enameloid organ with the
      species' fluoride (F) content in mature enameloid. Secretory-stage inner dental
      epithelial cells (IDE) of parrotfish (high F) and pufferfish (low F) secreted
      procollagen granules into the enameloid collagen matrix. The odontoblasts of both
      species, less numerous than IDE cells, also contained procollagen granules at the
      enameloid matrix formation stage. After the full thickness of enameloid matrix
      collagen had been deposited, enameloid crystallites formed parallel to the long
      axis of the enameloid collagen fibres. Concurrently, the plasma membranes of the
      outer dental epithelial cells (ODE) became invaginated in both species, but to a
      much greater extent in parrotfish. Highly undulating parrotfish ODE cells
      surrounded numerous fenestrated capillaries. In contrast, pufferfish ODE cells
      remained straight with few adjacent capillaries. Extensive tight junctions formed
      between ODE and IDE cells of both species, sealing the extracellular space. With
      increased mineralization, enameloid collagen fibres were no longer discernible. A
      thin layer of amorphous material, which subsequently mineralized, was secreted on
      to the enameloid surface by IDE cells in both species. Pufferfish odontoblasts
      secreted a mineralizing amorphous layer on the pulpal aspect of the enameloid.
      The results suggest that at the mineralization stage, a triad of cytostructural
      features, highly invaginated ODE cells, highly vascularized ODE cells, and
      extensive tight junctions are strongly correlated with high fluoride content of
      mature enameloid mineral. Species without any one of these features have lower
      fluoride in the enameloid.

PMID- 8141665
TI  - Effects of benzo(a)pyrene and nicotine on prostaglandin synthesis in buccal pouch
      and submandibular glands of the Syrian hamster.
AB  - Adult male Syrian hamsters were treated by swabbing the apex of the buccal pouch
      with corn oil (control, C), 1 mM benzo(a)pyrene (BP), nicotine (NC), or BP+NC in
      corn oil, twice daily, 5 days a week. After a 4-week treatment, the pouches and
      submandibular glands were dissected and used for the determination of endogenous
      prostaglandin (PG) production and studies on in vitro PG synthesis. Of the three
      PGs analysed (PGE2, PGF2 alpha and 6-keto-PGF1 alpha), PGE2 was predominant in
      the pouch and the glands. BP or NC alone had only a weak effect on PG synthesis
      in both tissues. However, the combination of BP and NC had a synergistic effect,
      causing diminished PG synthesis in both tissues. In buccal pouch, BP+NC
      significantly decreased the concentrations of endogenous PGE2 and PGF2 alpha
      (PGE2: 0.669 +/- 0.254 versus 1.698 +/- 0.460, PGF2 alpha: 0.273 +/- 0.090 versus
      0.625 +/- 0.272 ng/g tissue; BP+NC versus C; mean +/- SD, n = 5, p < 0.05).
      Similarly significant results were also found for in vitro PG synthesis (PGE2:
      0.541 +/- 0.249 versus 1.399 +/- 0.340, PGF2 alpha: 1.045 +/- 0.428 versus 2.133
      +/- 0.510 ng/g tissue; BP+NC versus C; mean +/- SD, n = 5, p < 0.05). In
      submandibular glands, BP+NC significantly diminished the concentration of
      endogenous PGE2 (1.183 +/- 0.175 versus 2.379 +/- 0.488 ng/g tissue; BP+NC versus
      C; mean +/- SD, n = 5, p < 0.05). The synthesis of 6-keto-PGF1 alpha in both
      tissues, and the synthesis of PGF2 alpha in submandibular gland, were slightly
      decreased with all treatments.

PMID- 8141666
TI  - Translocation of the alpha-isozyme of protein kinase C during stimulation of rat
      parotid acinar cells by phorbol ester and carbachol.
AB  - Protein kinase C activity was detected in the cytosolic fraction of quiescent
      parotid acinar cells; the particulate fraction contained a much smaller
      proportion of the enzyme. Protein kinase C activity was increased in the membrane
      fraction and decreased in the cytosol after exposure of intact cells to phorbol
      12-myristate 13-acetate (PMA) or the muscarinic-receptor agonist carbachol. The
      effect of PMA was potentiated by a subthreshold concentration of ionomycin.
      Immunoblot analysis with anti-protein kinase C antibodies revealed that the
      protein kinase C-alpha isoform is expressed in rat parotid cells. Other Ca(2+)
      dependent isoforms were not detected. Further, agonist stimulation caused the
      redistribution of protein kinase C-alpha from cytosol to a membrane fraction.
      Agonists may promote parotid acinar cell activity, including amylase secretion,
      by increasing the affinity of protein kinase C-alpha for the membrane fraction,
      presumably via a rise in Ca2+ and diacylglycerol derived from
      polyphosphoinositide hydrolysis.

PMID- 8141667
TI  - The fungicidal effect of human lactoferrin on Candida albicans and Candida
      krusei.
AB  - Five oral isolates each of Candida albicans and Candida krusei were studied for
      their sensitivity to the fungicidal effect of human lactoferrin. Significant
      inter- and intraspecies variations were observed and with most isolates the
      sensitivity of C. krusei to lactoferrin was greater than that of C. albicans.
      Fungicidal activity of lactoferrin was dose-dependent and observable only with
      the iron-free form of the molecule (apo-lactoferrin). Iron-saturated lactoferrin
      was ineffective against all isolates. Supernatant protein assays and scanning
      electron microscopy indicated cell surface alterations--leakage of proteins and
      formation of surface blebs--only in those Candida isolates that were sensitive to
      apo-lactoferrin. As lactoferrin is a common, non-immune, mucosal defence protein,
      its varying mode of action against C. albicans and C. krusei may be related to
      their different oral carriage rates.

PMID- 8141668
TI  - In vivo and in vitro study of the effects of chlorpromazine on tooth
      mineralization in rats and mice.
AB  - The effects of chlorpromazine (CPZ) on tooth mineralization were examined using
      incisor dentine in adult rats and cultured tooth germs of mandibular first molars
      dissected from mouse embryos. CPZ (10, 50 and 250 mg/kg, s.c.) substantially
      inhibited dentine mineralization as evaluated by contact microradiographs. Plasma
      calcium and phosphorus concentrations were not decreased by CPZ (10 and 50
      mg/kg). Physicochemical effects were not involved in the action of CPZ on the
      mineralization. In vitro experiments showed that CPZ (1 and 10 microM) inhibited
      mineralization and alkaline phosphatase (ALP) activity in the tooth germs. As CPZ
      has the properties of a calmodulin antagonist, the calmodulin antagonists W-7 and
      W-5 were also examined. Both inhibited mineralization and ALP activity in tooth
      germs; W-5 had less effect than W-7. These in vivo and in vitro findings suggest
      that CPZ inhibited cell-mediated mineralization in dentine without affecting the
      calcium-regulating system and physicochemical mineral deposition. In addition,
      calmodulin could be involved in cell-mediated mineralization.

PMID- 8141669
TI  - Fluoride-induced developmental changes in enamel and dentine of European roe deer
      (Capreolus capreolus L.) as a result of environmental pollution.
AB  - Using macroscopic, microradiographic and scanning electron-microscopic methods,
      the effects of increased fluoride exposure on enamel and dentine formation were
      studied in fluorosed mandibular premolars and molars of roe deer from the heavily
      industrialized Ruhr area, Germany. Macroscopically, fluorosed teeth were
      characterized by opaque and stained enamel and in more severe cases also by
      enamel surface lesions, reduction or loss of enamel ridges on their occlusal
      surfaces and increased wear. Microradiographically, fluorosed enamel exhibited
      different degrees of subsurface hypomineralization, in part apparently indicating
      a fluoride effect during enamel maturation. In some specimens, a pronounced but
      varying enhancement of the pattern of Retzius lines was observed throughout the
      enamel, denoting strongly intermittent fluoride exposure during enamel matrix
      secretion. This variation in exposure was also reflected histologically in
      dentine, by bands of interglobular dentine and marked accentuation of incremental
      lines. Microradiography of sections through enamel surface hypoplastic lesions
      showed the enamel forming the bottom and partly also the walls of the lesions to
      be highly mineralized. Scanning electron microscopy showed that the outer enamel
      along the more pronounced hypoplastic lesions consisted of stacked, thin layers
      of 'aprismatic' enamel, indicating that the ameloblasts in these areas had lost
      the distal (rod-forming) regions of their Tomes' processes. These observations
      demonstrate that the origin of enamel hypoplasias in deer clearly differs from
      that in rodents, where fluoride induces the formation of subameloblastic cysts.
      The differences in the degree of fluorotic alteration between the teeth of a
      single tooth row could be related to the developmental sequence of the dentition
      in roe deer. The roe deer is thus considered to be a very sensitive and useful
      bioindicator of environmental pollution by fluorides.

PMID- 8141670
TI  - Inhibitory commissural connections of neurones in the trigeminal motor nucleus of
      the rat.
AB  - Physiological evidence is presented for the existence of commissural fibres that
      cross the midsagittal plane in the medulla of the rat at the level of the
      trigeminal motor nucleus (Mo5). These fibres, which have their origin in the Mo5,
      terminated in the contralateral Mo5. Small inhibitory postsynaptic potentials
      were recorded in jaw-closing motoneurones by electrical activation of the
      commissural fibres; jaw-opening and fusimotor neurones as well as the jaw-closing
      and jaw-opening reflex were not affected. Electromyographic recordings from jaw
      closing and jaw-opening muscles in the unrestrained rat showed that masseter
      activity was inhibited by the commissural fibres. These trigeminal commissural
      connections might play a part in the co-ordination of bilateral activity of the
      jaw-closing musculature during unilateral chewing.

PMID- 8141671
TI  - Fluoride uptake in human dentine from glass-ionomer cement in vivo.
AB  - The purpose was to examine F uptake and distribution in dentine from a F
      containing glass-ionomer cement in vivo. Nine volunteers were selected from
      dental students who were scheduled for extraction of their third molars. Two
      cavities were prepared on the same occlusal surface of the third molars for each
      subject; one was restored with glass-ionomer cement (Virtabond), the other with
      zinc phosphate cement as a control. After 3 months the teeth were extracted. F
      profiles in the dentine from the cavity floor to the pulpal surface were
      determined in tissue immediately adjacent to the restorations. An abrasive micro
      sampling technique was used. The F concentration of the dentine was highest
      immediately beneath glass-ionomer cement filling, decreasing towards the pulpal
      surface. Overall F concentrations were greater in the dentine beneath the glass
      ionomer cement than in that beneath the zinc phosphate cement. It was concluded
      that the glass-ionomer cement markedly enhanced fluoride uptake by underlying
      dentine in vivo.

PMID- 8141672
TI  - Reproducibility of the human masseteric jaw-jerk reflex in association with the
      menstrual cycle.
AB  - The jaw jerk was elicited by chin taps in the relaxed masseter muscle of the
      preferred chewing side in five young females. Recordings were made during three
      randomized sessions and under standardized conditions: two sessions between the
      seventh and the 15th day of the female menstrual cycle and the third within the
      last 5 days of the cycle. Both latency and duration of the reflex were generally
      reproducible over time. Individual between-session variation was occasionally
      present, with a general tendency for lower values in the end-cycle session, but
      this did not affect the overall results. Systematic subject variation, such as
      central excitatory-state variance of the timing of the experiments, and possibly
      some other uncontrolled technical error, may have contributed to the observed
      variation.

PMID- 8141673
TI  - Diurnal variation in labelling index in human buccal epithelium.
AB  - Diurnal variations in the number of DNA-synthesizing cells (labelling index) in
      human buccal epithelium were studied by in vitro pulse labelling with tritiated
      deoxythymidine. Eleven male volunteers provided 33 biopsy specimens at six time
      periods. The results showed a 24-h periodicity in the labelling index in this
      tissue. The mean peak labelling index obtained at 22:00 h (3.20 +/- 0.18) was
      significantly different from the means obtained at the rest of the times. The 24
      h mean labelling index (labelled cells/100 cells) was 2.48 +/- 0.47 for three
      subjects who volunteered samples at all six time periods. The labelling index
      obtained around the middle part of the day for all subjects (2.44-2.59) appears
      to be representative of a 24-h basal or reference value.

PMID- 8141674
TI  - An immunocytochemical study of the innervation of developing human fetal teeth
      using protein gene product 9.5 (PGP 9.5).
AB  - Developing teeth of 32 human fetuses (crown-rump length 11-205 mm) were examined
      immunohistochemically by antisera to protein gene product 9.5 (PGP 9.5) in an
      attempt to shed light upon the possible role of innervation in odontogenesis. As
      a control for the specificity of PGP 9.5 as a neuronal marker, the results were
      verified by immunocytochemical co-localization in peripheral nerves of neurone
      specific enolase, neurofilaments and S-100 protein. The dental follicle received
      the first nerve fibres in the early cap stage. At this stage, fibroblasts
      differentiated in the presence of nerve fibres and formed the dental follicle
      surrounding the developing tooth. In the dental papilla, however, no fibres were
      demonstrated until the dentine and enamel matrices had formed, about half of the
      present height of the tooth germ. Most nerve fibres were localized in the basal
      part of the papilla until the last stage examined and usually followed the blood
      vessels of the papilla. Thus the effect of innervation on tooth development may
      be associated with the development of the dental follicle. A novel finding was
      that functional odontoblasts were not only positive for S-100 but also for PGP
      9.5, indicating their neural crest origin.

PMID- 8141675
TI  - Effect of sympathetic denervation of the pineal gland on maternal co-ordination
      of the circadian rhythm of alpha-amylase in parotid gland from young rats.
AB  - Twenty-five-day-old rats maintained in constant darkness since birth and born
      from mothers kept in the dark since the 14th day of pregnancy showed a circadian
      rhythm of alpha-amylase content in parotid glands, which may be explained by a
      mechanism of maternal co-ordination. Rats in the same conditions, except that
      their mothers had been submitted to bilateral excision of the superior cervical
      ganglia 30 days before mating, did not show diurnal variations of alpha-amylase
      activity in the parotid glands. When ganglionectomized mothers were treated with
      a daily dose of melatonin (1 mg/kg) from the 14th day of gestation up to the 10th
      day of lactation, their litters showed significant diurnal variations of amylase
      in the parotid glands, suggesting a role of the maternal pineal gland in the
      maternal-fetal and/or maternal-neonatal transfer of photoperiodic information.

PMID- 8141676
TI  - Lipid droplet accumulation and lipoprotein lipase activity in the rat salivary
      gland during the perinatal period.
AB  - The submandibular and sublingual glands of foetal and newborn rats aged 21 days
      in utero to 7 days after birth were examined morphologically and biochemically.
      Lipid droplets tended to be localized in secretory cells, especially in their
      basal cytoplasm. The degree of droplet accumulation varied with the age of the
      rat. No droplets were observed before and immediately after birth. The number of
      accumulated droplets peaked 24-48 h after birth, then gradually decreased and
      reached normal levels by 5 days. In the salivary glands of fasted newborn rats,
      no lipid droplets were observed throughout the experiment. The amount of
      triacylglycerol reached its maximum level 1 day after birth; it then decreased
      gradually until 5 days and after that did not change. The amount of cholesterol
      did not change during postnatal development. Lipase activity attained its maximum
      level in the salivary glands immediately after birth and then decreased rapidly.
      It was higher in the glands of fasted than fed 1-day-old rats. Antiserum against
      lipoprotein lipase inhibited the salivary gland lipase activity in a dose
      dependent manner, with 5 microliters of antiserum producing 60-70% inhibition.
      Non-immune serum had little effect. It was concluded that (1) accumulated lipid
      in the secretory cell cytoplasm of the salivary glands originates from ingested
      milk; (2) the principal component of accumulated lipid droplets is
      triacylglycerol; (3) 60-70% of the total lipase activity represents lipoprotein
      lipase; (4) an increase of lipoprotein lipase activity is recognizable before the
      accumulation of triacylglycerol.

PMID- 8141677
TI  - Two-dimensional electrophoresis of human salivary proteins from patients with
      sialoadenopathy.
AB  - Unstimulated saliva was fractionated by micro two-dimensional gel
      electrophoresis, and the proteins visualized by silver staining and
      immunostaining. The subjects with Sjogren's syndrome exhibited both quantitative
      and qualitative alterations in the protein composition of the saliva not only
      from the parotid gland but also from the submandibular/sublingual glands.

PMID- 8141678
TI  - The role of the general practitioner in aboriginal health.

PMID- 8141679
TI  - Aboriginal culture and the doctor-patient relationship.

PMID- 8141680
TI  - Social and cultural differences affect medical treatment.
AB  - This paper seeks to identify some of the significant health issues for Aboriginal
      people and the obstacles they often encounter in assessing the medical system.
      Clearly, the latter largely result from problems in communication, which can be
      addressed by seeking to establish good relationships. Whether the Aboriginal
      patients live in a traditional or remote community, a rural country area, or a
      large urban setting, an understanding of their conceptualization of their
      conditions can greatly enhance the communication process. Mobbs points out that
      this not only improves the clinical encounter, it also helps to overcome barriers
      of mistrust, misunderstanding and anxiety between the client and the
      professional.

PMID- 8141681
TI  - Women's business.
AB  - For Aboriginals, matters relating to reproduction are private and the preserve of
      women alone. At least one factor contributing to the high maternal and perinatal
      mortality in Aboriginals is the cultural inappropriateness of current health
      services. Future planning of maternal health services will be more effective if
      cultural imperatives of Aboriginal women are made a priority.

PMID- 8141682
TI  - Hansen's disease. Practice tips for management.
AB  - The author highlights some of the critical features of general practice diagnosis
      and management of Hansen's disease in First World primary care practice. These
      features are often not obvious or emphasised in most texts because they are
      designed for a Third World scenario, where primary care is delivered without the
      luxury of medically trained practitioners and therefore without the option of
      emergency steroid therapy.

PMID- 8141683
TI  - Hearing health needs for aboriginal and Torres Strait Islander people.

PMID- 8141684
TI  - Common health problems in Northern Territory aboriginal children.
AB  - Aboriginal children in the Northern Territory suffer health problems similar to
      children in Third World countries. The major problems are malnutrition,
      diarrhoeal disease and respiratory tract infections. Infections in all systems
      are common and low birth weight due in significant part to poor growth in utero
      is a major problem in the newborn period.

PMID- 8141685
TI  - Retained placenta.

PMID- 8141686
TI  - Removing plaster casts from children.

PMID- 8141688
TI  - All that is excreted does not glister: or why do we keep on collecting urine to
      measure creatinine clearance?

PMID- 8141687
TI  - Diagnosis of deep venous thrombosis: the role of selected investigational
      modalities.

PMID- 8141689
TI  - Hepatopulmonary syndrome--response to liver transplantation--new insights into an
      old problem.

PMID- 8141690
TI  - A comparative study of radionuclide venography and contrast venography in the
      diagnosis of deep venous thrombosis.
AB  - BACKGROUND: The value of the radionuclide blood pool venogram in detecting deep
      venous thrombosis (DVT) has to date been inadequately evaluated. This is despite
      its lower complication rate than the gold standard of contrast X-ray venography.
      AIMS: To compare the relative accuracy and inter observer variability of
      radionuclide blood pool and X-ray contrast venography as well as evaluate
      previous literature on radionuclide venography. METHODS: Prospective comparison
      of radionuclide and contrast venography was performed in 39 patients. Sensitivity
      and specificity of radionuclide venography were compared to contrast venography
      and confidence intervals were measured using standard error calculations. A meta
      analysis of previous studies was also performed. RESULTS: Significant inter
      observer variation in reports was present in both radionuclide (37%) and contrast
      (22%) venograms. Using consensus reports sensitivity of radionuclide venography
      was 87% compared to contrast venography and specificity was 83%. These results
      are similar to those obtained in previous studies. Furthermore, sensitivity in
      specificity in the proximal veins were 90% and 92% respectively which were
      superior to sensitivity and specificity in the distal veins where it was 74% and
      90% respectively. CONCLUSION: The radionuclide venogram appears accurate in the
      proximal veins and in excluding but not diagnosing distal venous thrombosis.

PMID- 8141691
TI  - Systemic lupus erythematosus in Australian aborigines: high prevalence, morbidity
      and mortality.
AB  - BACKGROUND: Racial differences occur in the incidence of systemic lupus
      erythematosus (SLE). It has been suggested that SLE occurs at a higher prevalence
      and with greater severity in Aboriginal Australians, but because of the small,
      widely distributed population base, this has not been well documented. AIMS: To
      confirm and document the clinical impression of an increased prevalence and
      severity of systemic lupus erythematosus (SLE) in Aboriginal Australians, and to
      identify prognostic indicators. METHODS: Top End Northern Territory (NT)
      Aborigines with SLE on 1 January 1984 or diagnosed thereafter were followed until
      1 January 1991. Epidemiological, clinical and serological data were collected.
      RESULTS: Prevalence on 1 January 1991 estimated at 1:1900, at least twice the
      estimated prevalence in non-Aboriginal Australians. High frequencies of renal
      disease (62% with proteinuria > 0.5 g/day) and autoantibodies to the Sm antigen
      (29%) were identified, contributing to the high mortality. Five year survival
      rate was 60%, with 67% of deaths resulting from infection. CONCLUSIONS: There is
      a high prevalence of SLE in NT Aborigines. In view of probable under-recognition
      of mild cases the true prevalence is likely to be even higher. Although morbidity
      and mortality may have been overestimated for the same reason, both were found to
      be high. Improved living conditions and health care delivery may improve
      prognosis.

PMID- 8141692
TI  - A comparison between enalapril and captopril on insulin sensitivity in
      normotensive healthy volunteers.
AB  - BACKGROUND: Captopril has been shown to improve insulin sensitivity in insulin
      resistant hypertensive individuals and enalapril has been shown to improve
      insulin sensitivity in a small group of healthy volunteers, but there has been no
      direct comparison of the effects of the different angiotensin converting enzyme
      inhibitors (ACEIs) on insulin sensitivity in either insulin sensitive or insulin
      insensitive populations. AIM: To compare the impact of two different ACEIs
      (captopril and enalapril) on insulin mediated glucose uptake in normotensive, non
      obese, insulin sensitive subjects. METHOD: A single blind cross-over study
      comparing captopril (6.25 mg twice daily) and enalapril (5 mg once daily) for 28
      days with a 28 day washout period between drugs. Insulin mediated glucose uptake
      was measured by means of the euglycaemic hyperinsulinaemic clamp at the start and
      completion of each period of drug therapy. RESULTS: Both drugs resulted in
      elevations of fasting insulin levels (mean difference +/- SEM for combined data,
      2.7 +/- 1.8; p < 0.05) and a reduction in insulin mediated glucose uptake (mean
      difference for combined data, -0.72 +/- 0.37 mg/kg-1 minute-1; p = 0.056).
      Results were similar for both agents and suggest a class effect. CONCLUSIONS: The
      increase in fasting insulin levels, and reduction in insulin mediated glucose
      uptake in this study are in contrast to findings in obese and hypertensive
      subjects, and indicate that studies of insulin sensitivity of ACEIs in non-obese,
      normotensive subjects are inappropriate for predicting likely effects in clinical
      practice.

PMID- 8141693
TI  - Prevention of heart disease by subcutaneous desferrioxamine in patients with
      thalassaemia major.
AB  - BACKGROUND: Cardiac siderosis from transfused iron remains the major cause of
      death in thalassaemia major, despite iron chelation therapy with desferrioxamine.
      AIMS: Our aim was to determine the nature and extent of cardiac involvement and
      its relationship to desferrioxamine use in a group with thalassaemia major.
      METHODS: We reviewed 76 patients with thalassaemia major and performed multiple
      logistic regression to analyse factors affecting cardiac involvement. Factors
      studied included: patient sex, age, haemoglobin, serum ferritin, total
      transfusions, liver iron, duration of desferrioxamine use, electrocardiograms,
      echocardiograms and compliance to desferrioxamine treatment. RESULTS: Thirty
      seven patients developed heart disease. They were older (p < 0.001), began
      desferrioxamine later (p < 0.001), had more liver iron (p = 0.014), higher serum
      ferritin levels (p = 0.023) and received more blood (p = 0.018). Compared to
      those with optimal compliance the odds of developing heart disease were increased
      10.7 times in fair compliers (p < 0.001) and 5.1 times in poor compliers (p =
      0.016). However, there was no significant difference between those with fair and
      poor compliance. After multivariate analysis only compliance (p = 0.02) and age
      at desferrioxamine onset (p = 0.004) remained significant. Compliance was
      inversely related to liver iron (p < 0.001), serum ferritin (p < 0.001) and age
      at desferrioxamine commencement (p < 0.001). CONCLUSIONS: We conclude that late
      commencement of desferrioxamine and noncompliance are associated with greater
      iron loading and an increased risk of heart disease.

PMID- 8141694
TI  - How vancomycin is used in Australasia--a survey.
AB  - BACKGROUND: Vancomycin serum concentrations have been monitored over the last 30
      years in an attempt to avoid dose-dependent toxicity and enhance efficacy.
      Current literature recommendations for peak and trough concentrations are usually
      in the range of 20-40 mg/L and 5-10 mg/L, respectively. Literature
      recommendations regarding the time at which peak concentrations are measured are
      highly variable, ranging from immediately after the end of the infusion to three
      hours post-dose. AIMS: To identify how vancomycin dosing is being monitored and
      assess variability in the current practice. METHODS: A survey of microbiology
      departments and infectious disease physicians in major Australasian hospitals was
      undertaken. The variability in the current practice was assessed by fitting mean
      recommendations to a two compartment Bayesian model. RESULTS: Of the 83 (70%) who
      replied 71 (86%) monitored vancomycin concentrations. Fifty-four percent targeted
      peak concentrations within the range of 20-40 mg/L, and 73% targeted trough
      concentrations < or = 10 mg/L. The time of sampling of peak concentrations varied
      considerably ranging from immediately (12%) to 120 minutes (12%) post-infusion
      (median 30 minutes [40%]). The concentration-time curves resulting from three
      sets of mean recommendations ('peaks' drawn at: 0, 30 and 120 minutes aiming for
      a concentration of 35 mg/L with a trough concentration of 10 mg/L) were modelled
      using a two compartment Bayesian programme. The predicted true peak (maximum)
      concentrations ranged from 30 to 86 mg/L, despite aiming for identical target
      concentrations, indicating marked variation in the actual dosing practice.
      CONCLUSIONS: There is thus considerable variation in the practice of vancomycin
      therapeutic monitoring which has a major effect on dosing. The main contributing
      factor is the variable timing of sampling peak concentrations.

PMID- 8141695
TI  - Capillary blood glucose measurements in hospital inpatients using portable
      glucose meters.
AB  - BACKGROUND: The use of portable glucose meters by nursing staff to perform
      bedside capillary blood glucose measurements is standard practice in the
      management of diabetic hospital inpatients. Few studies, however, have examined
      the practical limitations or the cost of this technology. AIM: To investigate the
      performance and cost of capillary blood glucose measurements using portable
      glucose meters in a hospital inpatient population being managed for diabetes
      mellitus. METHODS: The setting was a 500 bed metropolitan University Teaching
      hospital, with 22 meters (Glucometer-M) in routine use by about 450 accredited
      nursing staff. The Glucometer-M was also compared with an operator-independent
      meter (Hemocue) to assess the effect of operator bias on the overall efficacy and
      cost of the programme. RESULTS: Retrospective analysis of Glucometer-M reagent
      strips and comparison of measurements (n = 72) with the Hemocue revealed a marked
      operator bias which diminished accuracy and increased costs. The significant
      proportion of low haematocrits (< 30%) in the hospital population limited the
      applicability of the Glucometer-M which only operates reliably over the
      haematocrit range 35-50%. The excess of blood glucose measurements was
      highlighted by both a hospital ward audit and the frequency which exceeded that
      of routine electrolyte assays. CONCLUSIONS: Reliable bedside estimation of
      capillary blood glucose levels in hospitals requires a meter which is accurate,
      has negligible operator bias, is largely unaffected by haematocrit, and has
      insignificant risk of cross-contamination. At present only the Hemocue fulfils
      these specifications. Irrespective of meter choice, it is necessary to develop
      criteria for glucose measurements and monitor adherence.

PMID- 8141696
TI  - Managing asthma in accident and emergency departments: an assessment in non
      teaching hospitals.
AB  - BACKGROUND: The management and follow-up of asthma patients presenting at
      Accident and Emergency (A&E) departments have mostly been studied in children's
      hospitals or specialised teaching hospitals. AIMS: To study the adequacy of
      assessment, treatment and follow-up of patients presenting at A&E departments in
      non-teaching hospitals. To compare the assessment and management of asthma in A&E
      departments among hospitals in a health region. METHODS: A twenty-five per cent
      sample of presentations to A&E departments in all public hospitals in the
      Illawarra for one year was selected for a case note audit. Information on
      demographics, assessment, management and referral was extracted from the A&E case
      notes and medical records of cases with documentation of a final diagnosis of
      asthma. Chi square and Fischer's Exact tests were used for comparisons among
      hospitals. RESULTS: Of 359 presentations with a final diagnosis of asthma, 88%
      were self referred and only 5% were first presentations. Objective measures of
      airways obstruction was not documented in 34% of admissions and 48% of
      nonadmissions. There was no documented follow-up in 28% of cases. The assessment
      and management of asthma in A&E was significantly poorer in smaller hospitals.
      CONCLUSION: Evidence of high use of A&E as a primary care facility by asthma
      patients was found in the study. There is a need to implement protocols to
      optimise assessment and treatment of asthma in smaller hospitals.

PMID- 8141697
TI  - Cryptococcus neoformans in tropical northern Australia: predominantly variant
      gattii with good outcomes.
AB  - BACKGROUND: Infection with Cryptococcus neoformans is common in the Northern
      Territory of Australia. Disease is life threatening and treatment is prolonged
      and often complicated by the need for surgery and difficulties with medical
      therapy. AIMS: To document incidence, demography, risk factors, clinical features
      and outcomes of infection and to determine differences between gattii and
      neoformans varieties. METHODS: Case records of all patients (n = 35) diagnosed
      with cryptococcal infection at the Royal Darwin Hospital between 1976 and 1992
      were reviewed retrospectively. Current status of patients was ascertained.
      Variety identification of isolates was determined by growth in canavanine-glycine
      bromthymol blue agar. RESULTS: Of the 35 patients, 23 had meningitis, ten had
      pneumonia, one had a dermal infection and one had fungaemia with no obvious
      focus. Twelve (52%) meningitis cases and two (20%) pneumonia cases had no
      predisposing disease. Thirteen (57%) meningitis cases had concomitant pulmonary
      cryptococcosis. Twenty-nine patients with Aboriginal and six were Caucasian, with
      a relative risk for Aboriginals compared with non-Aboriginals of 20.6 (95% CI 8.6
      49.5). Arnhemland was the commonest location of infection, with an annual
      incidence in Aboriginals of 0.14/1000. Fourteen (78%) of 18 isolates tested were
      C. neoformans var. gattii. Management was characterised by the frequent need for
      adjunctive surgery and prolonged or repeat courses of systemic antifungal
      therapy. Despite this, long-term outcomes are encouraging with a mortality of 14%
      overall and 9% in meningitis patients. The river red gum (Eucalyptus
      camaldulensis) has a limited distribution in Arnhemland and ongoing studies are
      seeking alternative environmental sources of C. neoformans var. gattii.

PMID- 8141699
TI  - Computerised tomography does not predict N2 disease in patients with lung cancer.
AB  - BACKGROUND: Mediastinal node involvement in primary lung cancer determines the
      staging and prognosis of the patient, and as these nodes can be seen on the
      computerised tomography (CT) scan of the chest it is a temptation to diagnose
      malignant involvement if the nodes appear enlarged. However, initial experience
      with mediastinal node mapping at lung resection demonstrated this extrapolation
      to be unreliable and misinterpretation of enlarged nodes on CT may lead to
      misdiagnosis and prejudice the patient's management. AIM: To demonstrate that the
      sensitivity, specificity, and accuracy of the CT to detect malignant mediastinal
      nodes is too low to use size of node on CT as representative of malignant
      involvement. METHODS: One hundred and fifty-three sequential patients with
      resectable lung cancer were studied with preoperative CT. Two radiologists
      determined the preoperative T and N status from these studies with nodes of 1.5
      cm or larger diagnosed abnormal. These results were compared to the results of
      subsequent node mapping performed after lung resection. RESULTS: Sensitivity was
      found to be 26%, specificity to be 81% and overall accuracy 69%--too low to
      justify the diagnosis of N2 disease on size of 1.5 cm or larger. CT is not a
      valid means of diagnosing malignant involvement of mediastinal nodes.

PMID- 8141698
TI  - Interferon alpha and doxorubicin in malignant mesothelioma: a phase II study.
AB  - BACKGROUND: Malignant mesothelioma is a tumour which is generally resistant to
      chemotherapy. While the addition of interferon to chemotherapy improves response
      rates in some other malignancies, such a combination has not been evaluated in
      the treatment of mesothelioma. AIMS: To assess the anti-tumour effects and
      toxicity of interferon-alpha combined with doxorubicin in the treatment of
      pleural mesothelioma. METHODS: Twenty five patients (mean age 54 +/- 11 years)
      were enrolled in a phase II study. All patients had a confirmed histological
      diagnosis, measurable tumour, a life expectancy of at least three months, and no
      prior chemotherapy or interferon. Interferon alpha-2a, 9 x 10(6) U sc daily, was
      administered together with doxorubicin 25 mg per m2 i.v. weekly, for 12 weeks.
      Response status was assessed by tumour measurements on clinical examination and
      thoracic CT scans before and after treatment. RESULTS: A partial response was
      observed in four patients (16%; 90% CI, 8-30%), 11 remained stable, while six had
      progressive disease. Four patients withdrew within the first month because of
      toxicity. The median survival of all patients was 11 months (95% CI, 3-19). Dose
      modification as a result of toxicity was required in all patients. Lethargy,
      weight loss, leukopenia and vomiting were the most common side effects.
      CONCLUSIONS: The combination of interferon-alpha and doxorubicin showed only
      modest activity and was associated with significant toxicity. It cannot be
      recommended in the treatment of malignant pleural mesothelioma.

PMID- 8141700
TI  - Warfarin: is it time to reduce target ranges again?

PMID- 8141701
TI  - Percutaneous removal of pacemaker leads by a counter-traction method.

PMID- 8141702
TI  - The rhythm of running: can the heart join in?

PMID- 8141704
TI  - Migraine and somnambulism.

PMID- 8141703
TI  - Myocardial infarction and cerebral haemorrhage in a young body builder taking
      anabolic steroids.

PMID- 8141705
TI  - Guidelines to rheumatoid arthritis therapy.

PMID- 8141706
TI  - Platelet transfusion-related sepsis.

PMID- 8141707
TI  - Acute leukaemia following chemotherapy including etoposide for testicular
      carcinoma.

PMID- 8141708
TI  - Mixed essential cryoglobulinaemia in a woman with chronic active hepatitis C and
      cirrhosis.

PMID- 8141709
TI  - Disseminated histoplasmosis presenting with urinary tract symptoms.

PMID- 8141710
TI  - Community acquired viral hepatitis in New Zealand: a case of sporadic hepatitis E
      virus infection.

PMID- 8141711
TI  - Thrombolysis '93. Canberra, Australia. 1-3 July 1993.

PMID- 8141712
TI  - The GUSTO trial: background and baseline characteristics.
AB  - The GUSTO study was designed to test the hypothesis that achieving early
      sustained patency with a thrombolytic regimen in acute coronary thrombosis would
      improve mortality. Four regimens were compared. In 41,021 patients randomised,
      nearly 3000 of these were in Australia and New Zealand. These regimens were
      streptokinase (SK) with subcutaneous heparin (9841 patients), SK and intravenous
      heparin (10,410 patients), accelerated tissue plasminogen activator (t-PA) and
      intravenous heparin (10,396 patients) and combined SK and t-PA (10,374 patients).
      The patients were well matched for baseline characteristics. The mean time to
      treatment was two hours. The accompanying regimen of investigation and
      revascularisation was aggressive--58% receiving angiography (28% in Australia),
      15% angioplasty (5% in Australia) and 9% bypass surgery (4% in Australia). The
      GUSTO trial results should be interpreted in the light of these background
      observations.

PMID- 8141713
TI  - Mortality results in GUSTO.
AB  - The mortality results for the four arms of the GUSTO trial are presented. The 30
      day mortality results were as follows: streptokinase (SK) and subcutaneous
      heparin (n = 9796), 7.2%, SK and intravenous heparin (n = 10,377) 7.4%,
      accelerated tissue plasminogen activator (t-PA) and intravenous heparin (n =
      10,344) 6.3%, and combined SK and t-PA (n = 10,328) 7.9%. This is a relative risk
      reduction of 14% for the accelerated t-PA regimen compared with the two SK
      regimens equivalent to an absolute risk reduction of ten lives saved per 1000
      patients treated. Predefined subgroups who showed a greater benefit with t-PA
      versus SK were patients under the age of 75, anterior infarct location and those
      treated within four hours of onset of symptoms.

PMID- 8141714
TI  - Strokes and net clinical benefit.
AB  - The need for careful assessment of stroke incidence in a trial comparing highly
      effective thrombolytic regimens was recognised in the design of the GUSTO trial.
      There was a gradation of stroke incidence from 1.22% in the streptokinase (SK)
      and subcutaneous heparin group, to 1.4% in the SK and intravenous heparin group,
      1.55% in the tissue plasminogen activator (t-PA) and intravenous heparin group
      and 1.64% in the combination t-PA and SK group. The concept of net clinical
      benefit was developed to balance the adverse effect of stroke with the benefit of
      mortality reduction. On this analysis, the net clinical benefit favoured the
      accelerated t-PA regimen over the SK regimens.

PMID- 8141715
TI  - Issues raised by GUSTO.
AB  - The GUSTO trial raises several questions including the role of heparin in
      thrombolysis. The need for intravenous versus subcutaneous heparin with
      streptokinase (SK) has not been clarified in this trial. It is more likely that
      the superiority of tissue plasminogen activator (t-PA) was due to its accelerated
      administration rather than the accompanying heparin. Despite the improvement in
      survival, much is still to be achieved in obtaining optimal reperfusion rates.

PMID- 8141716
TI  - Early thrombolytic treatment in acute coronary thrombosis.
AB  - It is now accepted that the earliest event in acute myocardial infarction is
      coronary occlusion caused by fissuring of an atherosclerotic plaque, with
      resultant platelet deposition on the mural flaw and build up of thrombus within
      the lumen. The symptoms generated are caused by myocardial ischaemia, as first
      described by Herrick and Levine some 80 years ago. If occlusion is not relieved,
      irreversible damage (infarction) begins in the ischaemic region within 30
      minutes, is half completed by 2.5 hours, and is virtually completed by six hours.
      Thrombolysis is now accepted therapy for acute evolving myocardial infarction,
      but in most cases such therapy is not commenced for four hours after symptom
      onset, when most of the irreparable damage has already been done and when the
      potential for benefit has fallen substantially. The average time to thrombolysis
      in GUSTO worldwide, however, was two hours and, in Australia, 2.8 hours. Only
      patients who could be submitted to thrombolysis within six hours of the onset of
      pain were included. The results of thrombolytic therapy in acute thrombosis are
      likely to be improved if delays are minimised. This requires education of the
      public in the symptoms of this condition, and on the actions to take if such
      symptoms arise. It also requires expeditious transfer to hospital (or appropriate
      treatment outside) and above all it requires expeditious assessment and treatment
      when patients arrive in hospital. Use of the diagnosis 'myocardial infarction'
      for such patients implies that irreversible damage has already occurred and
      serves as a disincentive for the speedy, aggressive management that is logical
      and appropriate for dissolution of the offending coronary thrombus.

PMID- 8141717
TI  - LATE assessment of thrombolytic efficacy with alteplase (rt-PA) six-24 hours
      after onset of acute myocardial infarction.
AB  - Conflicting results on the benefit of thrombolytic therapy administered six to 24
      hours after the onset of myocardial infarction (MI) led to the LATE trial. Five
      thousand seven hundred and eleven patients were treated with recombinant tissue
      plasminogen activator (t-PA) or placebo, treatment was begun between six and 24
      hours after the onset of infarction. For patients treated within 12 hours, there
      was a relative reduction in 35 day mortality of 25%, but no benefit for those
      treated at 12 to 24 hours. The benefits were confined to those whose treatment
      was begun within three hours of admission to hospital. These results widen the
      window for effective treatment from six to 12 hours after the onset of
      infarction, but emphasise the need for expeditious treatment when the diagnosis
      of MI is suspected.

PMID- 8141718
TI  - Repeat thrombolysis.
AB  - Since 20% of patients with myocardial infarction (MI) have had a previous
      infarction, and reinfarction within one year after infarction occurs in 9% of
      cases, it is important to clarify the role of repeat thrombolysis. After
      streptokinase (SK) administration, IgG antibodies rise to a peak at two weeks and
      slowly fall over the next 12 months, but 50% of patients still have antibody
      levels sufficient to neutralise a standard dose of SK up to four years after
      initial SK administration. On this evidence, SK or anistreplase should not be
      readministered, except perhaps in the first two to three days after initial
      treatment. The efficacy of tissue plasminogen activator (t-PA) and urokinase is
      not affected by prior treatment with SK.

PMID- 8141719
TI  - The role of angioplasty in acute myocardial infarction.
AB  - The role of primary angioplasty versus thrombolytic therapy for the treatment of
      coronary thrombosis has been the subject of recent randomised trials. They have
      shown a higher early patency rate after angioplasty with no differences in later
      patency. Recurrent ischaemia was more frequent after thrombolysis, but the one
      study that examined myocardial salvage showed no difference. There were fewer
      intracerebral bleeds in the angioplasty group, but owing mostly to much higher
      than usual stroke occurrence in the thrombolysis group. With less than 800
      patients in all the studies, no final conclusions can yet be drawn about effects
      on mortality and larger studies are needed. Primary angioplasty is an option when
      operators are skilled and the procedure can be done quickly.

PMID- 8141720
TI  - Reperfusion injury, stunning and myocardial viability.
AB  - Recent experimental data suggest that current thrombolytic strategies may not yet
      have achieved their full potential for myocardial salvage. In fact, reperfusion
      may result in microvascular and myocardial cellular injuries. These may translate
      into transient loss of contractile function ('myocardial stunning'), and possibly
      contribute to the ultimate extent of myocardial necrosis. A number of imaging
      modalities are now available to detect the presence and amount of these
      dysfunctional but viable myocardial segments. Myocardial reperfusion experiments
      using animal models have studied possible mechanisms responsible for reperfusion
      injury. These may help in the search for novel pharmacological and other
      adjunctive approaches which may overcome potential adverse effects of
      reperfusion.

PMID- 8141721
TI  - Post thrombolysis management.
AB  - Strategies for the evaluation of the post infarction patient need revision in the
      light of recent findings from thrombolytic trials, and the availability of more
      effective methods for detecting myocardial viability. A strategy based on
      determining the risk of re-occlusion from vessel anatomy at coronary angiography
      and determining the area of myocardium at risk based on sequential analysis of ST
      segment elevation is discussed.

PMID- 8141722
TI  - New thrombolytic strategies.
AB  - Recent angiographic studies after thrombolytic therapy have shown that the rates
      of effective coronary reperfusion (TIMI grade 3) is still quite low with
      currently available thrombolytic regimens. Approaches to improving thrombolytic
      efficacy include the development of mutants of t-PA, recombinant staphylokinase
      and conjugations of thrombolytic agents to monoclonal antibodies targeted to
      components of the thrombus. The development of more potent conjugative
      antithrombolysis therapy includes newer antiplatelet agents and selective
      thrombin inhibitors such as hirudin and Hirulog. Clinical trials of these new
      approaches are now underway and hold hope for improvement of reperfusion efficacy
      in coronary thrombolysis.

PMID- 8141723
TI  - GUSTO II trial.
AB  - The GUSTO II trial will investigate the role of antithrombin therapy in acute
      coronary syndromes, comparing standard doses of heparin with the specific
      antithrombin agent recombinant hirudin. The two drugs will be compared as primary
      therapy in patients with unstable angina or patients with myocardial infarction
      (MI) unsuitable for thrombolysis, and as post thrombolysis treatment in patients
      who fulfil standard criteria for thrombolysis therapy. A total of 12,000 patients
      will be studied in a global, multifactorial trial.

PMID- 8141724
TI  - Hirudin and Hirulog.
AB  - A brief outline is presented of a proposed trial of Hirulog versus heparin after
      thrombolytic therapy with streptokinase (SK). The lower patency rates achieved
      with SK compared with tissue plasminogen activator (t-PA) suggest that a potent
      thrombin specific agent may be more important for SK than for t-PA therapy. This
      study will involve more than 400 patients with two dose levels of Hirulog.
      Endpoints will be angiographic patency, and ST segment monitoring showing
      evidence of coronary reperfusion.

PMID- 8141725
TI  - Thrombolysis '93--overview and conclusions.

PMID- 8141726
TI  - Local reaction and serological response in commercial layer chickens injected
      intramuscularly in the leg with oil-adjuvanted Mycoplasma gallisepticum bacterin.
AB  - The incidence of local vaccine reaction was investigated in three flocks of
      commercial layer chickens after they were vaccinated intramuscularly in the leg
      with oil-adjuvanted Mycoplasma gallisepticum (MG) bacterin by commercial crews.
      Local vaccine reaction typically involved swelling due to a granulomatous
      cellulitis in the connective tissue above the tibiotarsal joint of the vaccinated
      leg. Histopathology revealed that the inflammatory reaction was confined
      primarily to subcutis and muscle fascia and rarely extended into muscle fibers,
      tendons, or tendon sheaths. Movement of the vaccinated flocks from growing to
      laying houses was associated with a significant increase in the incidence and
      severity of leg swelling. Antibodies against MG as measured by the
      hemagglutination-inhibition test were significantly higher in chickens with
      severe leg swelling than in chickens without leg swelling.

PMID- 8141727
TI  - Effect of induced molting on the severity of intestinal lesions caused by
      Salmonella enteritidis infection in chickens.
AB  - A study was conducted to describe the intestinal lesions caused by Salmonella
      enteritidis infection in 20-, 40-, and 74-week-old white leghorn chickens that
      were undergoing a feed deprivation-induced molt. The chickens were infected on
      the fourth day after feed was removed. At 4 days postinfection (8 days of feed
      deprivation), cecal and cecal tonsil inflammation was significantly greater in
      molted infected chickens than in unmolted infected chickens. The cecal lamina
      propria and epithelium of molted infected chickens contained heterophilic
      infiltrates, and there were heterophils and sloughed epithelial cells in cecal
      lumina. Colonic inflammation, consisting of heterophils infiltrating lamina
      propria and epithelium, occurred more often in molted infected chickens than in
      unmolted infected chickens. Immunoperoxidase staining of intestinal sections from
      20- and 40-week-old chickens revealed S. enteritidis antigen in the lamina
      propria of cecum, cecal tonsil, and occasionally the colon of molted infected
      chickens. The character of the S. enteritidis-induced intestinal lesions
      associated with molting was similar for different ages of birds.

PMID- 8141728
TI  - Effect of a defined continuous-flow derived bacterial culture and dietary lactose
      on Salmonella typhimurium colonization in broiler chickens.
AB  - A defined bacterial culture protective against Salmonella typhimurium cecal
      colonization in broiler chicks was derived utilizing a continuous-flow (CF)
      culture apparatus. Chicks receiving the CF culture in combination with a diet
      containing dietary lactose were protected against cecal colonization by S.
      typhimurium. The culture consisted of a mixture of gram-positive and gram
      negative facultative and strictly anaerobic bacteria. The isolates were
      identified as Enterococcus avium, two strains of Enterococcus faecalis
      (designated A and B), Lactococcus lactis, Lactobacillus animalis, a Lactobacillus
      that could not be identified to species level (designated strain CMS),
      Citrobacter freundii, Escherichia coli, E. fergusonii, Bifidobacterium animals,
      and Propionibacterium acidipropionici. Results indicated that CF cultures can be
      used as a tool to identify bacteria which are antagonistic to S. typhimurium in
      the chick cecum.

PMID- 8141729
TI  - A comparison of three isolation methods for obtaining immunoglobulin A from
      turkey bile.
AB  - Turkey IgA was isolated from bile by three methods: ammonium sulfate
      precipitation, polyethylene glycol (PEG) extraction, and lambda-carrageenan
      extraction. The isolated immunoglobulin fractions were compared using double
      diffusion, immunoelectrophoresis (IE), and enzyme-linked immunosorbent assay
      (ELISA). Results indicated that all three methods of isolation are sufficient for
      the initial isolation step for purification of the immunoglobulin fraction in
      turkey bile. Because of contaminating IgG, IgM, and other high-molecular-weight
      proteins, further purification by column chromatography is needed to isolate pure
      IgA. The lambda-carrageenan extraction method appears to be the method of choice
      for precipitating the immunoglobulin fraction in bile, because of the high
      antibody activity after extraction. Like ammonium sulfate precipitation, lambda
      carrageenan and PEG extraction are not sufficient as single-step purification
      methods and should be used as the initial step in the purification of IgA.

PMID- 8141730
TI  - Efficacy in chickens of a herpesvirus of turkeys recombinant vaccine containing
      the fusion gene of Newcastle disease virus: onset of protection and effect of
      maternal antibodies.
AB  - The onset of protection against Newcastle disease and the effect of maternal
      antibodies to Newcastle disease virus (NDV) and Marek's disease virus (MDV) on
      vaccine efficacy were determined following vaccination of chickens with a
      recombinant herpesvirus of turkeys (HVT) vaccine expressing the fusion (F)
      glycoprotein gene of NDV. Onset of protection following intra-abdominal
      administration of the recombinant HVT/F vaccine at 1 day of age and subsequent
      ocular challenge with the neurotropic velogenic Texas GB strain of NDV was
      determined to occur between days 14 and 21 post-vaccination (PV). Vaccination
      with the Hitchner B1 strain of NDV resulted in protection by day 6 PV, and
      vaccination with an inactivated NDV oil-emulsion vaccine induced protection by
      day 14 PV. One-day-old broiler-type chickens with maternal antibodies to both NDV
      and MDV and 1-day-old specific-pathogen-free (SPF) white leghorn chickens lacking
      maternal antibodies were vaccinated with the recombinant HVT/F vaccine or with
      control vaccines, challenged intra-abdominally with the very virulent RB1B strain
      of MDV on day 8 PV, and challenged with the Texas GB strain of NDV on day 29 PV.
      The HVT/F and NDV strain Hitchner B1 vaccines provided 73% and 80% protection,
      respectively, against NDV in broilers, whereas both vaccines resulted in 100%
      protection in SPF leghorns.

PMID- 8141731
TI  - Role of circulating maternal anti-rotavirus IgG in protection of intestinal
      mucosal surface in turkey poults.
AB  - The effect of circulating maternally transferred IgG on immunity of turkey poults
      to rotavirus infections was investigated. Specific-pathogen-free (SPF) turkey
      hens were hyperimmunized with avian group A rotavirus 2 weeks before the laying
      cycle. SPF poults designated positive for group A rotavirus (Rab+) and negative
      for such maternal antibody (Rab-) were challenged orally with the homologous
      virus at 2, 5, or 12 days of age (challenge Groups 1, 2, and 3, respectively).
      Poults were examined at 3 and 6 days postinfection (PI) for clinical signs, gross
      lesions, histopathological changes in the small intestine, rotavirus in
      intestinal contents, and D-xylose absorption as an indicator of the intestinal
      absorptive function. In challenge Groups 1 and 2, rotavirus titers in the
      intestinal contents were significantly lower in Rab+ poults than in Rab- poults
      at 3 days PI. Gross lesions and D-xylose absorption results were consistent with
      the virus-shedding data. Histopathological changes were moderate and comparable
      in Rab- and Rab+ poults. In challenge Group 3, however, no significant
      differences were observed between Rab- and Rab+ poults in any of the examined
      parameters. Results provided evidence that circulating maternally derived IgG has
      an important role in protection of the intestinal mucosa against rotavirus
      infection during the first week of life. It is suggested that protective immunity
      afforded by maternal IgG is titer-dependent.

PMID- 8141732
TI  - Effectiveness of dietary propionic acid in controlling Salmonella typhimurium
      colonization in broiler chicks.
AB  - Newly hatched broiler chicks were provided a corn/soybean meal-based ration
      treated with propionic acid at 30 mumol/g of feed ration. At 3 days of age, the
      chicks were challenged orally with 10(4) Salmonella typhimurium. Crop contents
      from 4-day-old chicks that were provided dietary propionic acid contained
      significantly higher concentrations of propionic acid (4.0 to 6.8 mumol/g crop
      contents) than crops from challenged control chicks provided untreated feed (0.9
      to 1.5 mumol/g crop contents). Provision of dietary propionic acid on feed as a
      dry powder in five trials or a liquid application in three trials had no
      significant effect on crop or cecal pH. Significant decreases in Salmonella in
      the crop and ceca were detected in one trial, but the decreases were likely the
      result of the presence of anti-salmonellae bacteria rather than the dietary
      propionic acid. Results indicate that propionic acid in the feed was ineffective
      in reducing Salmonella infection in the crop and ceca.

PMID- 8141733
TI  - A model for testing the efficacy of enrofloxacin (Baytril) administered to turkey
      hens in the control of Mycoplasma iowae infection in eggs and embryos.
AB  - In a preliminary experiment, a field infection with Mycoplasma iowae was
      simulated by inoculating turkey eggs with various doses of two strains of M.
      iowae immediately before incubation. The strain and dose chosen for further study
      were those that best multiplied and resulted in infection of embryos from which
      the organism could be isolated after 25 days of incubation. Ten turkey hens free
      from infection with mycoplasmae were housed in isolation. The hens were given
      enrofloxacin in the drinking water at a concentration of 50 ppm on 3 successive
      days, on two occasions at intervals of 14 days. Within 48 hours of lay, their
      eggs were each inoculated with 0.1 ml of the selected strain and dose (10(5)
      colony-forming units/ml) of M. iowae. M. iowae was recovered from almost all eggs
      laid by hens before the initial medication but not from any of the eggs laid for
      several days after each period of medication. Thereafter, the organism could be
      recovered from a high proportion of inoculated eggs. The treatment of infected
      turkey laying flocks with enrofloxacin at strategic periods might be helpful in
      the control of this Mycoplasma by limiting both vertical and horizontal
      transmission.

PMID- 8141734
TI  - Immunoprophylaxis of Salmonella enteritidis infection by lymphokines in Leghorn
      chicks.
AB  - Chickens were treated prophylactically with the soluble products from Con A
      stimulated T-lymphocytes from Salmonella enteritidis-infected chickens in order
      to investigate the effect of such prophylactic treatment on organ invasion by S.
      enteritidis. At 18 days of age, chicks were injected intraperitoneally with one
      of the following: A) the Amicon YM 10 ultrafiltrate from immunized chickens, B)
      the Amicon YM 10 ultraretentate material from immunized chickens, or C) the
      Amicon YM 10 ultraretentate material from control nonimmune chickens. Thirty
      minutes after lymphokine injection, all birds were challenged per os with 10(8)
      colony-forming units of S. enteritidis. At both 1 and 6 days post-challenge,
      prophylactic treatment of chickens with the immune retentate resulted in a 51-60%
      reduction in S. enteritidis organ invasion. The reduction in S. enteritidis organ
      invasion was associated with a significant increase in lamina propria thickness
      based on morphometric analysis (P < 0.05). These results demonstrate that the
      prophylactic administration of S. enteritidis-immune lymphokines induces
      protection against S. enteritidis organ invasion, which is associated with a
      measurable microanatomical change in the cecal mucosa.

PMID- 8141735
TI  - Pasteurella multocida virulence factors: selection of fowl cholera-inducing and
      non-inducing strains.
AB  - Relatively little information is available on Pasteurella multocida virulence
      factors involved in producing fowl cholera. Because of the complex nature of
      bacterial pathogenesis, the recommended approach for ascertaining these factors
      is to compare biological attributes of high- and low-virulence strains. To permit
      use of this approach for fowl cholera, P. multocida strains of high and low
      virulence were identified. Turkey poults were exposed intrapharyngeally and
      intravenously (IV) to two antigenically and biochemically similar strains. Based
      on mortality, strain P-1059 was highly virulent and strain P-1062 was avirulent.
      Microbiological examination indicated that only the virulent strain infected the
      pharyngeal mucosa of intrapharyngeally exposed poults and survived and multiplied
      in IV-exposed poults. These findings indicate strain differences in those
      virulence factors concerned with the colonization and multiplication stages of
      disease development.

PMID- 8141736
TI  - Cross-protection studies with Pasteurella multocida bacterins prepared from
      bacteria propagated in iron-depleted medium.
AB  - Strains X-73 (serotype 1) and P-1059 (serotype 3) of Pasteurella multocida, avian
      origin, expressed additional membrane proteins (MPs) when grown in brain-heart
      infusion (BHI) broth containing the iron chelator dipyridyl and when grown in BHI
      broth treated with the iron chelator Chelex 100. These additional MPs were not
      detected when both strains were grown in BHI broth. Chickens and turkeys were
      vaccinated twice with inactivated oil-emulsion vaccines containing bacterial
      cells expressing these MPs or with vaccines containing bacterial cells grown in
      BHI broth. Two weeks after the final vaccination, all birds were challenged to
      determine whether bacterins made from P. multocida that had been propagated in
      conditions of iron deprivation would induce heterologous serotype immunity. The
      bacterins produced in medium low in iron did not consistently induce significant
      protection against heterologous challenge.

PMID- 8141737
TI  - Immunoglobulin receptors used in avian Mycoplasma identification.
AB  - Among 77 isolates of avian Mycoplasma examined, IgG receptors were demonstrated
      on six of the nine species represented. Species identified with receptors were:
      Mycoplasma gallisepticum (two receptors of approximately 84,000 and 75,000
      molecular weight [MW]), M. gallinarum (one receptor of approximately 135,000 MW),
      M. pullorum (one receptor of approximately 130,000 MW), M. gallinaceum (one
      receptor of approximately 125,000 MW), M. iowae (two receptors of approximately
      50,000 and 38,000 MW), and M. synoviae (two receptors of approximately 91,000 and
      81,000 MW). The IgG receptors demonstrated in Western blots consistently
      identified each of the six species. No IgG receptors were detected on M. iners,
      M. gallopavonis, or M. meleagridis.

PMID- 8141738
TI  - Evaluation of the efficacy of oil-emulsion bacterins for reducing fecal shedding
      of Salmonella enteritidis by laying hens.
AB  - Two replicate experiments were conducted to test the efficacy of two different
      Salmonella enteritidis oil-emulsion bacterins (an experimentally prepared acetone
      killed vaccine and a commercially available vaccine) for protecting laying hens
      against intestinal colonization following oral exposure to S. enteritidis. Each
      vaccine was administered twice (4 weeks apart), and all hens were challenged with
      10(8) cells of a nalidixic-acid-resistant S. enteritidis strain 2 weeks after the
      second vaccination. Fecal samples from vaccinated and unvaccinated control hens
      were cultured at three weekly intervals post-challenge to determine the incidence
      of intestinal colonization and the numbers of S. enteritidis shed into the
      environment. Both vaccines significantly reduced the incidence of intestinal
      colonization (P < 0.05) and the mean number of S. enteritidis cells shed in the
      feces (P < 0.01) at 1 week post-challenge. However, the degree of protection
      afforded by vaccination was only partial, as more than half of the vaccinated
      hens still shed substantial numbers of S. enteritidis. If used in conjunction
      with other flock sanitation and infection-monitoring strategies, vaccination with
      bacterins could potentially reduce the overall level of environmental
      contamination and thereby also reduce the horizontal transmission of S.
      enteritidis within and between laying flocks.

PMID- 8141739
TI  - Association of K-1 capsule, smooth lipopolysaccharides, traT gene, and Colicin V
      production with complement resistance and virulence of avian Escherichia coli.
AB  - A group of complement-resistant, virulent avian Escherichia coli isolates were
      compared with a group of complement-sensitive, avirulent avian isolates for the
      presence of K-1 capsule, smooth lipopolysaccharides (LPS), the traT gene, and
      Colicin V (ColV) production. These parameters were selected because of their
      reported association with complement resistance and virulence in E. coli.
      Lethality in chicken embryos has also been shown to be correlated with virulence
      of avian E. coli for chickens. The complement-resistant, virulent E. coli
      isolates did not possess a K-1 capsule. Production of ColV and the presence of
      smooth LPS were significantly correlated with embryo lethality. There was no
      correlation between the presence of traT and embryo lethality. These results
      suggest that complement resistance and virulence in avian E. coli are associated
      with ColV production and smooth LPS but not with K-1 antigen or traT.

PMID- 8141741
TI  - Susceptibility to Eimeria tenella of chickens and chicken embryos of partly
      inbred lines possessing homozygous major histocompatibility complex haplotypes.
AB  - Susceptibility to Eimeria tenella infection of chicken embryos and chickens of
      partly inbred lines possessing different major histocompatibility complex
      haplotypes was investigated. Chicken embryos of line H-B2 possessing B2
      homozygous haplotype showed lower mortality and higher oocyst production than
      embryos of line H-B15 possessing B15 homozygous haplotype. Embryos of line H-B2
      chickens were considered more resistant to E. tenella infection than those of
      line H-B15. Seven days after 10-day-old chickens were infected with E. tenella,
      the two lines showed no significant differences in percent bodyweight gain, cecal
      lesion score, and oocyst production; they differed significantly only in cecal
      shrinkage. Results suggest that the B system affects chicken embryos and chickens
      differently in susceptibility to E. tenella infection.

PMID- 8141740
TI  - Identification and characterization of a Mycoplasma synoviae 55,000-molecular
      weight antigen associated with hemagglutination.
AB  - Serological studies have shown that some antigenic determinants are conserved
      among several pathogenic Mycoplasma species, including Mycoplasma pneumoniae, M.
      genitalium, and M. gallisepticum. M. synoviae, an avian pathogen that shares
      certain morphological and biological features with the above-mentioned
      mycoplasmas, was examined by the protein immunoblot procedure for its reactivity
      with hyperimmune rabbit antiserum specific for the major (190,000 molecular
      weight [MW]) adhesion P1 protein of M. pneumoniae. A single polypeptide of M.
      synoviae of approximately 55,000 MW was recognized by the anti-P1 antiserum. The
      55,000-MW antigen was electroeluted following electrophoretic separation of M.
      synoviae polypeptides, and the eluted protein was used for immunization of mice
      for the production of monoclonal antibodies (MAbs) and polyclonal antiserum.
      Immunoelectron microscopy with MAbs and gold-conjugated secondary antibodies
      showed that the 55,000-MW antigen was located at the cell surface and was more
      densely clustered around the bleb-like protuberance of the cell. Immuno-affinity
      purified 55,000-MW antigen, as well as the antibodies produced against it,
      blocked the hemagglutination by M. synoviae.

PMID- 8141742
TI  - Chlamydiosis in a captive group of Houbara bustards (Chlamydotis undulata).
AB  - A chlamydiosis outbreak occurred in a Houbara bustard (Chlamydotis undulata)
      captive breeding group in Saudi Arabia, inducing peracute deaths, highly variable
      clinical signs, and pathological and histological lesions. Typical inclusion
      bodies in stained impression smears of spleen and prevalence (80%) of antibodies
      against Chlamydia, detected by a competitive enzyme immunoassay test, provided
      the bases for the diagnosis. This is the first report on a chlamydiosis outbreak
      in birds of the family Otididae.

PMID- 8141743
TI  - Facial cellulitis associated with fowl cholera in commercial turkeys.
AB  - Severe cephalic swelling and facial cellulitis in turkeys associated with fowl
      cholera were present in seven accessions submitted to two laboratories in a 2
      year period. Flocks ranged in age from 6 to 18 weeks and included both toms and
      hens. Interestingly, turkeys with facial cellulitis had no gross internal lesions
      of fowl cholera, whereas birds with gross lung, liver, and air-sac lesions did
      not have swollen heads. Histologically, the facial cellulitis was characterized
      by extensive fibrinonecrotic inflammation of the deep dermis with heterophilic
      perivasculitis and thrombosis. Additional characterization of Pasteurella
      multocida isolates from these cases was conducted retrospectively from
      lyophilized cultures. Serogrouping, serotyping, and an enzyme-linked
      immunosorbent assay (ELISA) for dermonecrotic factor were performed. All isolates
      were serogroup A or unencapsulated. Serotype 1 was the most prevalent serotype
      isolated in association with facial cellulitis. ELISA results for dermonecrotic
      toxin were inconclusive.

PMID- 8141744
TI  - Reovirus associated with excessive mortality in young bobwhite quail.
AB  - Multiple submissions of bobwhite quail (Colinus virginianus) were received for
      diagnosis from a commercial-size quail operation. The history and clinical signs
      included respiratory distress, lethargy, and substantial mortality. Reovirus was
      recovered from quail in the first submission, and both reovirus and adenovirus
      were isolated from later submissions. To determine the pathogenicity of the
      isolated reovirus, the initial isolate was inoculated into young quail from a
      different source. Those inoculated by the subcutaneous route became lethargic,
      and more than half died during the 2 weeks of the trial. Reovirus was recovered
      from a high percentage of those inoculated by this route. To the authors'
      knowledge, the isolation of reovirus from quail has rarely been reported, and
      reovirus has never before been suggested as a pathogen in this species.

PMID- 8141745
TI  - Postmortem findings of ostriches submitted to the Oklahoma Animal Disease
      Diagnostic Laboratory.
AB  - A review of 121 ostrich necropsies from the files at the Oklahoma Animal Disease
      Diagnostic Laboratory was conducted. The birds ranged in age from unhatched
      embryos to 4 years; the majority were less than 3 weeks old. The most common
      cause of death was ostrich chick fading syndrome (OCFS). OCFS is characterized by
      depression, anorexia, and death 3-5 days after onset of clinical signs in
      ostriches less than 3 weeks old. Escherichia coli and/or Klebsiella pneumoniae
      were isolated from various organs in these cases, and mortality ranged from 40%
      to 100%. Other conditions observed were edema in chicks associated with high
      incubator humidity levels, aspergillosis, leg deformities, and impaction of the
      proventriculus.

PMID- 8141746
TI  - Duck viral enteritis in domestic muscovy ducks in Pennsylvania.
AB  - Duck viral enteritis (DVE) outbreaks occurred at two different locations in
      Pennsylvania in 1991 and 1992. In the first outbreak, four ducks died out of a
      group of 30 domestic ducks; in the second outbreak, 65 ducks died out of a group
      of 114 domestic ducks, and 15 domestic geese died as well. A variety of species
      of ducks were present on both premises, but only muscovy ducks (Cairina moschata)
      died from the disease. On necropsy, gross lesions included hepatomegaly with
      petechial hemorrhages, petechial hemorrhages in the abdominal fat, petechial
      hemorrhages on the epicardial surface of the heart, and multifocal to coalescing
      areas of fibrinonecrotic material over the mucosal surface of the trachea,
      esophagus, intestine, and cloaca. Histologically, the liver had random multifocal
      areas of necrosis and eosinophilic intranuclear inclusion bodies in hepatocytes.
      DVE virus was isolated and identified using muscovy duck embryo fibroblast
      inoculation and virus neutralization.

PMID- 8141747
TI  - Diagnosis of favus (avian dermatophytosis) in Oriental breed chickens.
AB  - Chickens of various Oriental breeds (Shamo and Aseel) and crossbreeds in
      California's Central Valley were observed to have an unusual skin condition and
      feather loss. The appearance of white plaques on the comb, face, and/or ear lobes
      was followed by feather loss starting at the caudal base of the comb and
      progressing down the neck. Although the cocks were affected first, the condition
      spread to the hens paired with those cocks. The birds showed no other signs of
      illness. The affected areas were scraped and biopsied. The samples were examined
      histologically and by culturing on Sabouraud's dextrose agar and dermatophyte
      test medium. Microsporum gallinae, the causative agent of favus (avian
      dermatophytosis), was identified by the histological and mycological tests.

PMID- 8141748
TI  - Cataracts and crooked toes in Brahma chickens.
AB  - In 1991, 69% of the cockerels and 15% of the pullets in an inbred flock of
      approximately 200 dark and light Brahma chickens had unilateral or bilateral
      cataracts and crooked toes. Affected chickens were normal at hatching but
      developed cataracts with or without crooked toes by 6 months of age. The
      cataracts were initially focal and polar but progressed to be diffuse throughout
      the lenticular cortex. The crooked toes involved one or more of the second,
      third, and fourth digits and were due to a medial deviation of the distal aspect
      of the first phalanx. The cataracts and crooked toes were considered likely due
      to a hereditary defect, based on the following: the history of flock inbreeding;
      the lack of historical, clinical, or pathological evidence of avian
      encephalomyelitis or Marek's disease; the presence of lesions only in Brahma
      chickens and not in the approximately 200 other chickens on the farm kept under
      the same management and environmental conditions; the age at which the lesions
      occurred; and the nature of the lesions.

PMID- 8141749
TI  - Metastatic malignant melanoma in a mandarin duck (Aix galericulata).
AB  - A biopsy taken from a mass on the dorsal surface of the bill of an adult female
      mandarin duck (Aix galericulata) was diagnosed as a malignant melanoma by light
      microscopy. Two months later, the tumor had enlarged considerably; the duck
      developed severe dyspnea and was euthanatized. At necropsy, there were metastases
      to lymphoid tissues in the lower regions of the neck. To our knowledge, this is
      the first report of a malignant melanoma in a mandarin duck.

PMID- 8141750
TI  - Egg-production drop in turkeys associated with alphaviruses: eastern equine
      encephalitis virus and Highlands J virus.
AB  - Alphaviruses were isolated from tracheas of turkey breeders in two North Carolina
      flocks experiencing a severe drop in egg production. Highlands J virus was
      isolated from one of the breeder flocks, in which production decreased by as much
      as 72.6% in selected houses over a 48-to-96-hour period. Eastern equine
      encephalitis virus was isolated from the second breeder flock, which experienced
      an egg-production drop of 44.5%. Clinical signs in both flocks were similar, with
      inactivity and the egg-production drop being the only clinical signs observed.
      Eggs from affected breeders were small and white, and a few were soft-shelled.
      Sera collected from the flocks 2 to 3 weeks after production began dropping
      confirmed the presence of antibodies to the viruses recovered. In the first
      flock, egg production failed to return to above 50%, although heat stress may
      have played a role in production recovery. The second flock was taken out of
      production and recycled.

PMID- 8141751
TI  - Spirochetosis in California game chickens.
AB  - An outbreak of spirochetosis occurred in a flock of 75 game chickens in
      California during fall 1991. Affected birds were weak and anemic. Many had
      greenish diarrhea. Spirochetes were seen on Giemsa-stained blood smears and in
      silver-stained tissue sections of kidney, liver, and spleen. Splenomegaly, which
      is reported to be characteristic of fowl spirochetosis, was not observed in two
      acutely infected chickens.

PMID- 8141752
TI  - Tuberculosis in commercial emus (Dromaius novaehollandiae).
AB  - Extensive granuloma formation typical of tuberculosis was observed in a mature
      female emu. The diagnosis was confirmed by demonstration of acid-fast bacilli in
      lesions and culture of a Mycobacterium with growth characteristics resembling M.
      avium from liver tissue. Individual emus on the affected farm and an
      epidemiologically related unit gave a positive skin reaction to intradermal M.
      avium tuberculin. The implication of tuberculosis in commercial emus is noted in
      relation to the growth of the industry in North America and to management and
      commercial practices that encourage dissemination of infection within the species
      and to other exotic and domestic animals.

PMID- 8141753
TI  - Characterization of surface markers present on cells infected by chicken anemia
      virus in experimentally infected chickens.
AB  - Specific-pathogen-free chickens were infected with chicken anemia virus (CAV) at
      1 day of age and killed after 6 days. Using a double-antibody staining procedure,
      spleen, thymus, and bone-marrow cells containing CAV antigen were stained for
      presence of T-cell antigens and chicken major histocompatibility complex (MHC)
      Class 1 and 2 antigens. The results demonstrated CAV infection of precursor T
      cells in the thymus and of mature T-lymphocytes in the spleen. A significant
      proportion of the cells infected in bone marrow expressed MHC Class 2 antigens
      but did not exhibit the characteristics of T-lymphocytes. Since CAV grows in MDCC
      MSB1 cells, the staining characteristics of these cells were also studied. MSB1
      cells possessed all of the characteristics of mature, helper T-lymphocytes.

PMID- 8141754
TI  - Cellular response of the respiratory tract of chickens to infection with
      Massachusetts 41 and Australian T infectious bronchitis viruses.
AB  - Cellular response of chickens to infection with infectious bronchitis virus (IBV)
      was investigated by lavage of the respiratory tract of five 2-week-old specific
      pathogen-free (SPF) chickens at 2, 8, 24, 48, 72, and 96 hours postinfection (PI)
      with either Massachusetts 41 (IBV-M41) or Australian T (IBV-T) IBV. Tissue
      response was monitored by microscopic examination of trachea and lung from five
      non-lavaged infected chickens collected at the same intervals. The total number
      of cells recovered by lavage from IBV-M41-infected chickens was dramatically
      higher than the total number recovered from IBV-T-infected chickens and
      uninfected controls. By contrast, the total number of cells recovered from IBV-T
      infected chickens was no higher than that of the uninfected chickens. Heterophils
      constituted the majority of inflammatory cells recovered from both IBV-M41
      infected and IBV-T-infected chickens. Heterophil numbers in IBV-M41-infected
      chickens paralleled total cell-number recovery, whereas heterophil numbers in IBV
      T-infected birds were no higher than those in uninfected chickens. The number of
      lymphocytes recovered from IBV-M41-infected chickens increased 72 hours PI and
      continued to increase for the duration of the study. Lymphocyte numbers in IBV-T
      infected chickens exceeded those in uninfected chickens only at 96 hours PI. The
      number of lavage macrophages in IBV-M41-infected chickens increased earlier than
      the number of lymphocytes but later reached a plateau. IBV-T macrophage numbers
      did not exceed those of uninfected chickens. Tissue damage occurred most
      consistently in the trachea and occurred when lavage heterophil numbers were
      rising or at their peak. Lavage cell recovery and composition reflected tracheal
      mucosa inflammatory cell infiltrate.

PMID- 8141755
TI  - Newcastle disease virus passage in MDBK cells as an aid in detection of a
      virulent subpopulation.
AB  - Newcastle disease virus strains (NDV) La Sota, Texas GB (GB), and mixtures of the
      two strains were serially passaged in embryonated chicken eggs or the MDBK cell
      line, a more restrictive culture system than eggs for NDV. The two culture
      systems were compared by evaluating culture harvests for pathogenicity in
      inoculated chickens; the harvests were identified by hemagglutination-inhibition
      tests against monoclonal antibodies that can differentiate La Sota and GB
      cultures. Both viruses, inoculated alone or as mixtures, were propagated by
      passage in chicken eggs. La Sota strain failed to propagate by continuous passage
      in MDBK cells, and only GB was identified in culture harvests propagated in MDBK
      cells that had been inoculated with GB or mixtures of GB and La Sota. The results
      indicate that the MDBK cell line is a more selective substrate than chicken eggs
      and suggest that passage in MDBK cells may aid in selecting for more virulent
      subpopulations of NDV in a mixed culture. Other reference NDV strains, pigeon NDV
      isolates, and recent lentogenic NDV isolates from chickens were also passaged in
      MDBK cells; all strains except those that are classified as lentogens like La
      Sota could be serially propagated in MDBK cells.

PMID- 8141756
TI  - Isolation and characterization of a Haemophilus paragallinarum mutant that lacks
      a hemagglutinating antigen.
AB  - In an in vivo cross-protection test with Haemophilus paragallinarum strains of
      serovars B and C, we isolated and characterized a mutant strain, S1M, which
      lacked a hemagglutinating (HA) antigen when compared biologically and
      immunologically with isogenic strain S1. Unlike the isogenic strain S1, the
      mutant strain S1M lacked HA activity against formaldehyde-fixed chicken
      erythrocytes, even after hyaluronidase treatment, and it did not stimulate
      hemagglutination-inhibition antibody in chickens immunized with bacterial cells.
      Dot-blot testing and immunoelectron microscopy with monoclonal antibodies against
      serovar C-specific HA antigens showed that strain S1M did not react with these
      monoclonal antibodies. Furthermore, strain S1M was found to be both non
      pathogenic and non-immunogenic. In contrast, the isogenic strain S1 reacted with
      these monoclonal antibodies and was pathogenic and immunogenic. These results
      suggest that the HA antigen of H. paragallinarum serovar C. strain plays an
      important role in pathogenicity and immunogenicity.

PMID- 8141757
TI  - Isolation of Salmonella from ovaries and oviducts from whole carcasses of spent
      hens.
AB  - Spent hens containing hard-shelled eggs were obtained to study the influence of
      sample collection and sample preparation methodology on the detection of
      Salmonella in ovaries. Four hundred eighteen birds from 19 flocks were collected,
      and the carcasses were opened aseptically within 8-12 hours of collection. A
      sample set containing hard-shelled egg, ovary, and oviduct section were collected
      from each carcass, and surface contaminants were removed from ovaries with
      polyoxyethylene ether. Three of 19 flocks (15.8%) and six of 407 ovary samples
      were positive for Salmonella; two oviduct samples were positive (0.5%). No eggs
      were Salmonella-positive. Single and multiple serotypes were detected in ovaries.
      Results indicated that Salmonella recovery rates can be significantly affected by
      speed in processing samples after collection, by cleanliness of the tissue
      collection environment (laboratory vs. slaughter plant), and by removal of
      surface contaminants.

PMID- 8141758
TI  - A comparative study of Mycoplasma gallisepticum vaccines in young chickens.
AB  - Ten-day-old leghorn chickens were vaccinated with the F, ts-11, or 6/85 strain of
      Mycoplasma gallisepticum (MG) via the intraocular route or subcutaneously with MG
      bacterin and challenged by aerosol with the R strain of MG at 30, 60, or 90 days
      post-vaccination. Respiratory reaction post-vaccination, serological response,
      persistence of the vaccine strain, and protection against aerosol challenge were
      compared. In general, the ts-11 and 6/85 strains induced a milder post
      vaccination reaction than F-strain, produced a weaker serological response, and
      did not persist as long in the upper respiratory tract. The F-strain-vaccinated
      chickens had the fewest and mildest air-sac lesions post-challenge, the 6/85 and
      ts-11 groups had somewhat less protection, and bacterin-vaccinated chickens had
      no detectable protection against airsacculitis. The F-strain-vaccinated chickens
      also had the fewest MG organisms in the trachea 10 days postchallenge.

PMID- 8141759
TI  - Effect of amprolium on production, sporulation, and infectivity of Eimeria
      oocysts.
AB  - Amprolium reduced the number of oocysts shed by Eimeria acervulina, E. maxima, E.
      necatrix, and a mixture of susceptible strains of E. tenella. Sporulation of
      oocysts from mediated chickens was reduced compared with that of oocysts from
      unmedicated chickens. Sporulation was reduced by levels of 0.0250% amprolium for
      E. acervulina and by levels of 0.0060% for E. maxima and the susceptible E.
      tenella. Not enough oocysts were recovered to measure sporulation of E. necatrix.
      Sporulation reduction was not affected by the method of administration of
      amprolium (feed or water), except with E. acervulina, for which fewer oocysts
      sporulated when 0.0120% amprolium was added in the drinking water than when
      0.0125% amprolium was added to the feed. Conversely, amprolium medication had no
      effect on the sporulation of an amprolium-resistant E. tenella. When fed to
      unmedicated chickens, those oocysts from amprolium-medicated chickens that did
      sporulate were as infective as oocysts recovered from unmedicated chickens.

PMID- 8141760
TI  - The relation of egg specific gravity to the incidence of spontaneous
      cardiomyopathy in tom turkeys.
AB  - The specific gravity and weight of eggs were determined for two groups of 600
      eggs each, originating from Nicholas and British United Turkey of America (BUTA)
      turkey breeder flocks. A total of 137 Nicholas and 190 BUTA toms hatched from
      these eggs were used for the experiment. At days 21, 33, 40, 47, 56, and 61, toms
      that showed retarded growth were euthanatized, along with a corresponding number
      of normal birds. Both groups were measured for body weight, heart weight,
      separate weights of left and right ventricles, and combined atrial weight. At
      market age, the remaining toms were weighed, and the hearts were checked at
      processing for lesions characteristic of spontaneous turkey cardiomyopathy (STC).
      STC was found in 10.2% of Nicholas and 8.4% of BUTA toms. No correlation could be
      found between specific gravity of eggs and incidence of STC. Body weights of
      affected toms were reduced during the growing period. At processing, 2.8% of toms
      had lesions of STC, and mean body weight was 1298 g lower than average. The
      ratios of combined atrial weight:body weight, right ventricular weight:body
      weight, left ventricular weight:body weight, and total heart:body weight were
      significantly higher at all times in affected toms than in controls, and the
      differences were the greatest at 3 weeks of age.

PMID- 8141761
TI  - Increased salt concentration reversibly destabilizes p53 quaternary structure and
      sequence-specific DNA binding.
AB  - Growth suppression by p53 correlates with sequence-specific DNA binding and is
      determined by tertiary and quaternary protein structures. Exposure to 300 mM NaCl
      did not affect p53 tertiary structure, but dissociated high-molecular-mass
      complexes with concomitant loss of specific DNA binding. Both effects were
      reversible. We conclude that high salt can reversibly destabilize the quaternary
      structure of p53 that is most efficient for sequence-specific DNA binding.

PMID- 8141762
TI  - Platelet-derived growth factor-induced phosphatidylinositol 3-kinase activation
      mediates actin rearrangements in fibroblasts.
AB  - Various agonist-induced cell responses in neutrophils and fibroblasts, such as
      chemotaxis and cytoskeletal rearrangements, have been shown to correlate with the
      synthesis of PtdIns(3,4,5)P3; however, the significance of this rise in second
      messenger levels is not clear. We show here that wortmannin inhibits platelet
      derived growth factor (PDGF)-mediated production of PtdIns(3,4,5)P3 in human
      foreskin fibroblasts with an IC50 of about 5 nM. A similar inhibition was
      observed in in vitro assays (IC50 approximately 1 nM) with phosphatidylinositol 3
      kinase immunoprecipitated by antibodies directed against the 85 kDa subunit
      (p85). On the other hand, wortmannin did not affect PDGF-mediated phosphorylation
      of p85 as detected by immunoprecipitation with anti-phosphotyrosine antibodies,
      and did not dissociate the complex of p85 and the catalytic subunit (p110) of
      phosphatidylinositol 3-kinase. These results are consistent with a direct,
      specific inhibition of the enzyme by wortmannin at concentrations relevant for
      its previously reported effects on cellular responses. When stimulated with PDGF,
      human foreskin fibroblasts form circular structures of filamentous actin.
      Preincubation of these cells with wortmannin inhibits PDGF-mediated actin
      rearrangements, suggesting a need for PtdIns(3,4,5)P3 formation as a signal for
      this cell response.

PMID- 8141763
TI  - The post-translational processing of chromogranin A in the pancreatic islet:
      involvement of the eukaryote subtilisin PC2.
AB  - The post-translational processing of chromogranin A (CGA) and the nature of the
      enzyme(s) involved were investigated in rat pancreatic islet and insulinoma
      tissue. Pulse-chase radiolabelling experiments using sequence-specific antisera
      showed that the 98 kDa (determined by SDS/PAGE) precursor was processed to an N
      terminal 21 kDa peptide, a C-terminal 14 kDa peptide and a 45 kDa centrally
      located peptide with a rapid time course (t1/2 approx. 30 min) after an initial
      delay of 30-60 min. The 45 kDa peptide was, in turn, converted partially into a 5
      kDa peptide with pancreastatin immunoreactivity and a 3 kDa peptide with WE-14
      immunoreactivity over a longer time period. Incubation of bovine CGA with rat
      insulinoma secretory-granule lysate produced peptides of 18, 16 and 40 kDa via
      intermediates of 65 and 55 kDa. N-terminal sequence analysis indicated that
      cleavage occurred at the conserved paired basic sites Lys114-Arg115 and Lys330
      Arg331, suggesting that cleavage of the equivalent sites (Lys129-Arg130 and
      Lys357-Arg358) in the rat molecule produced the initial post-translational
      products observed in intact pancreatic beta-cells. The enzyme activity
      responsible for the cleavage of bovine CGA co-chromatographed on DEAE-cellulose
      with the type-2 proinsulin endopeptidase and with PC2 immunoreactivity. The type
      1 enzyme (PC1/3) appeared inactive towards CGA. The requirement for Ca2+ ions and
      an acidic pH for conversion was consistent with the involvement of a member of
      the eukaryote subtilisin family, and the composition of the released peptides in
      pulse-chase and secretion studies suggested that conversion occurred in the
      secretory-granule compartment. The overall catalytic rate as well as the relative
      susceptibilities of the Lys114-Arg115 and Lys330-Arg331 sites to cleavage were
      affected by pH, suggesting that the ionic environment of the processing
      compartment may play a role in the differential processing of CGA which is
      evident in various neuroendocrine cells.

PMID- 8141764
TI  - DNA polymerase alpha-primase complex from the silk glands of the non-mulberry
      silkworm Philosamia ricini.
AB  - The DNA content in the silk glands of the non-mulberry silkworm Philosamia ricini
      increases continuously during the fourth and fifth instars of larval development
      indicating high levels of DNA replication in this terminally differentiated
      tissue. Concomitantly, the DNA polymerase alpha activity also increases in the
      middle and the posterior silk glands during development, reaching maximal levels
      in the middle of the fifth larval instar. A comparable level of DNA polymerase
      delta/epsilon was also observed in this highly replicative tissue. The DNA
      polymerase alpha-primase complex from the silk glands of P. ricini has been
      purified to homogeneity by conventional column chromatography as well as by
      immunoaffinity techniques. The molecular mass of the native enzyme is 560 kDa and
      the enzyme comprises six non-identical subunits. The identity of the enzyme as
      DNA polymerase alpha has been established by its sensitivity to inhibitors such
      as aphidicolin, N-ethylmaleimide, butylphenyl-dGTP, butylanilino-dATP and
      antibodies to polymerase alpha. The enzyme possesses primase activity capable of
      initiating DNA synthesis on single-stranded DNA templates. The tight association
      of polymerase and primase activities at a constant ratio of 6:1 is observed
      through all the purification steps. The 180 kDa subunit harbours the polymerase
      activity, while the primase activity is associated with the 45 kDa subunit.

PMID- 8141765
TI  - Unmethylated thyroglobulin promoter may be repressed by methylation of flanking
      DNA sequences.
AB  - The thyroglobulin gene, like many other tissue-specific genes, appears to be
      specifically less methylated in the differentiated cell type where it is
      transcribed. The thyroglobulin gene promoter elements themselves are highly CG
      deficient and do not contain any HpaII/MspI sites. In this study, using DNA
      constructs that were methylated in vitro with HpaII or MspI methylases, we show
      that DNA methylation of vector sequences is sufficient to repress the activity of
      the thyroglobulin gene promoter in transient transfection experiments. Reporter
      gene expression from a plasmid containing only the proximal thyroglobulin gene
      promoter is sensitive to DNA methylation even in fully differentiated thyrocytes.
      Transcription from methylated plasmids containing the thyroglobulin gene enhancer
      and proximal promoter is also clearly reduced when the transfected cells are
      maintained under less-differentiated conditions. These results indicate that DNA
      methylation can influence, from a distance, the activity of an unmodified
      promoter. Our results also agree with the view that loss of DNA methylation does
      not constitute a prerequisite for thyroglobulin gene expression in differentiated
      thyrocytes, where the thyroglobulin gene enhancer and promoter are activated.
      However, the production of thyroglobulin transcripts could be severely impaired
      when this activation is not maximal, as is the case in less-differentiated cells
      or when the enhancer element is lacking. We suggest that DNA methylation helps to
      maintain the thyroglobulin gene in an inactive state unless all of the conditions
      required for its expression are fulfilled, and that the thyroid-specific
      demethylation events are a consequence of the activation state of the gene.

PMID- 8141766
TI  - Intracellular Ca2+, inositol 1,4,5-trisphosphate and additional signalling in the
      stimulation by platelet-activating factor of prostaglandin E2 formation in P388D1
      macrophage-like cells.
AB  - In the P388D1 macrophage-like cell line, phospholipase A2 activity and
      prostaglandin production are stimulated by platelet-activating factor (PAF) and
      bacterial lipopolysaccharide (LPS). We have investigated the role of Ins(1,4,5)P3
      and Ca2+ in signal transduction of PAF-induced prostaglandin E2 (PGE2) formation
      in these cells. The role of Ca2+ in the activation mechanism was studied by
      fluorescence imaging of intracellular Ca2+ in individual adherent cells and by
      determining the PGE2 production in the same population of cells. This new
      approach enabled us to correlate directly events on the single-cell level with a
      physiologically relevant response of the cell population. Priming the cells with
      LPS was required for PAF to stimulate PGE2 formation, yet LPS affected neither
      the intracellular free Ca2+ concentration ([Ca2+]i) nor the PAF-induced rise in
      [Ca2+]i. In addition, basal and PAF-stimulated Ins(1,4,5)P3 levels were not
      affected by LPS priming. However, the Ca2+ transient, the release of Ins(1,4,5)P3
      and the formation of PGE2 induced by PAF were inhibited in cells pretreated with
      pertussis toxin. Buffering the [Ca2+]i with intracellular BAPTA [bis-(o
      aminophenoxy)ethane-NNN'N'-tetra-acetic acid] blocked the PAF-stimulated rise in
      [Ca2+]i and PGE2 formation. Removal of extracellular Ca2+ during PAF stimulation
      prevented the influx of Ca2+, but did not affect the initial [Ca2+]i transient,
      nor did it inhibit PGE2 formation. Under the same conditions, ionomycin
      stimulated an identical [Ca2+]i transient, but, in contrast with PAF stimulation,
      no PGE2 formation was observed. PGE2 production could be rescued by prompt
      subsequent addition of PAF, which caused no further [Ca2+]i change on its own.
      These results show that the transient initial rise in [Ca2+]i, produced either by
      PAF via the formation of Ins(1,4,5)P3 or directly by ionomycin, is necessary, but
      not sufficient for the formation of PGE2 in LPS-primed P388D1 cells. Furthermore,
      we have demonstrated for the first time that PAF triggers a second signal that is
      not mediated by a change in [Ca2+]i. However, both signals are required to induce
      PGE2 formation.

PMID- 8141768
TI  - Radiation inactivation of proteins: temperature-dependent inter-protomeric energy
      transfer in ox liver catalase.
AB  - The radiation-inactivation method is widely used to determine the oligomeric
      structure of enzymes without need for solubilization or purification. We have
      used purified ox liver catalase, a tetrameric enzyme in solution, to study energy
      transfer between associated promoters responsible for oligomer inactivation.
      However, after freeze-drying the tetramer dissociates into an asymmetric dimer.
      In the present paper we compare both the radiation-inactivation size (obtained by
      following the activity decay) and the target size (obtained by measuring the
      amount of remaining protein by SDS/PAGE) of catalase under various states of
      aggregation and temperature. At -78 degrees C, only one promoter was fragmented
      after being hit by a gamma-ray and, as expected, this protomer was also
      inactivated. This result was obtained when either catalase was in tetrameric or
      in dimeric forms. However, at 38 degrees C, even though a single monomer was
      fragmented as at -78 degrees C, the whole dimer was inactivated. This result
      suggests that, at the higher temperature, there is a transfer of energy from the
      fragmented protomer to the other associated protomer, causing inactivation of the
      whole dimer. The inactivation of oligomeric enzymes is a two-step mechanism
      involving: (1) fragmentation of the hit monomer, followed by (2) temperature
      dependent energy transfer from the fragmented towards the associated protomer.
      Thus we conclude that the radiation-inactivation size reflects the transfer of
      absorbed energy inside the oligomer which causes inactivation of one or several
      monomers.

PMID- 8141767
TI  - Isolation of a novel inducible rat heat-shock protein (HSP70) gene and its
      expression during ischaemia/hypoxia and heat shock.
AB  - Most of the members of the mammalian heat-shock protein (HSP) gene family have
      been studied and isolated from human and mouse cells. Few studies have
      concentrated on the HSPs of rat, a commonly used experimental animal. We have
      isolated and characterized a novel inducible rat HSP70 gene using an HSP70 cDNA
      sequence obtained from an ischaemic rat heart cDNA library. The isolated rat
      HSP70 gene was found to be a functional gene, as indicated by RNAase-protection
      and Northern-blot analysis. The deduced amino acid sequence of the inducible rat
      HSP70 exhibits a high degree of similarity to previously isolated mammalian
      inducible HSP70 gene products. Expression of the inducible HSP70 gene in rat
      myogenic cells (H9c2) is markedly increased after relatively short periods of
      hypoxia as well as by heat shock. Two heat-shock elements (HSE) are present in
      the rat HSP70 promoter. Transient transfection of rat HSP70
      promoter/chloramphenicol acetyltransferase constructs into H9c2 cells shows that
      the presence of either of the two HSEs is sufficient for heat-shock inducibility.
      In contrast, induction of the rat HSP70/chloramphenicol acetyltransferase
      constructs by hypoxia is only detectable when both HSEs are present. This leads
      us to conclude that the induction of HSP70 by hypoxia and heat shock occurs
      through the same regulatory HSEs but the activation of the inducible HSP70 gene
      by heat shock is several-fold higher than by hypoxia.

PMID- 8141770
TI  - Activation of NADPH oxidase involves the dissociation of p21rac from its
      inhibitory GDP/GTP exchange protein (rhoGDI) followed by its translocation to the
      plasma membrane.
AB  - Activation of the NADPH oxidase of phagocytes involves the small GTP-binding
      protein p21rac. In this paper we report that neutrophil cytosol contains
      predominantly p21rac2 rather than p21rac1, and that the P21rac2 is almost
      entirely complexed with rhoGDI (GDP dissociation inhibitor) to form a heterodimer
      with a molecular mass of 45-50 kDa. Activation of superoxide production by
      phorbol 12-myristate 13-acetate or formylmethionyl-leucyl-phenylalanine in whole
      cells, and by SDS in the cell-free assay, led to the dissociation of some of the
      p21rac2 from rhoGDI and its movement to the plasma membrane together with p47phox
      and p67phox. The appearance of these proteins at the plasma membrane was related
      to the dose of the agonist and to the rate of superoxide generation. The
      nucleotide bound to p21rac2 in this complex following isolation was almost
      exclusively GDP, with less than 2% GTP, and the complex was active in the cell
      free assay. Although the rac/GDI complex could activate the NADPH oxidase in the
      absence of exogenous GTP, the rate of superoxide production was increased 3-fold
      by the addition of GTP and was almost completely inhibited by GDP. Our findings
      confirm that rhoGDI serves as GDP dissociation inhibitor and that the release of
      p21rac2 from this inhibitor is an important step in activation of the NADPH
      oxidase.

PMID- 8141769
TI  - Stimulation of low-density lipoprotein uptake in HepG2 cells by epidermal growth
      factor via a tyrosine kinase-dependent, but protein kinase C-independent,
      mechanism.
AB  - Epidermal growth factor (EGF), a potent mitogenic polypeptide, stimulated the
      uptake and degradation of [3H]sucrose-labelled low-density lipoprotein (LDL) by
      HepG2 cells. The increase in LDL uptake was prevented by the presence of the
      tyrosine kinase inhibitor genistein. Activation of protein kinase C with phorbol
      12-myristate 13-acetate (PMA) also stimulated the uptake of [3H]LDL by HepG2
      cells. When EGF and PMA were added together, PMA increased the response to EGF in
      an additive manner. The protein kinase C inhibitor Ro-31-8220 prevented the
      increase in LDL uptake caused by PMA, but did not affect EGF stimulation of LDL
      uptake. Similarly, down-regulation of protein kinase C activity by chronic
      treatment with PMA also did not affect the EGF stimulation of LDL uptake. These
      results suggest that the EGF stimulation of LDL uptake and degradation by HepG2
      cells is mediated by a tyrosine kinase-dependent, but protein kinase C
      independent, mechanism.

PMID- 8141771
TI  - Purification and some properties of an IMP-specific 5'-nucleotidase from yeast.
AB  - An IMP-hydrolysing enzyme was purified to homogeneity from yeast extract. It was
      a soluble protein with an apparent molecular mass of 220 kDa, with a subunit
      molecular mass of 55 kDa. It was highly specific for IMP, and there was virtually
      no detectable activity with the other purine and pyrimidine nucleotides tested,
      including AMP and dIMP. The enzyme had a pH optimum of 6.0-6.5. Its activity was
      absolutely dependent on bivalent metal salts: Mg2+ was most potent, followed by
      Co2+ and Mn2+. The velocity/substrate-concentration plot of the enzyme was
      slightly sigmoidal (h = 1.7) and the s0.5 was 0.4 mM. ATP stimulated the enzyme
      by decreasing both h and s0.5. Diadenosine tetraphosphate stimulated the enzyme
      as effectively as ATP. Although the properties of the enzyme are similar to those
      of the IMP/GMP 5'-nucleotidase identified in various animals [Itoh (1993) Comp.
      Biochem. Physiol. 105B, 13-19], the substrate specificity of the former was much
      more strict than the latter.

PMID- 8141772
TI  - Pancreatic plasma membranes: promiscuous partners in membrane fusion.
AB  - We have developed a system in which the fusion of pancreatic plasma membranes
      with zymogen granules can be studied in vitro. We show here that pancreatic
      plasma membranes fuse not only with pancreatic zymogen granules but also with
      parotid secretory granules. In contrast, parotid membranes fuse only with parotid
      granules and not with pancreatic granules. The extent of fusion is insensitive to
      Ca2+ for all combinations of plasma membranes and granules. Guanosine 5'-[gamma
      thio]triphosphate (GTP[S]), on the other hand, stimulates fusion of pancreatic
      membranes with both pancreatic granules and parotid granules, but inhibits fusion
      between parotid membranes and parotid granules.

PMID- 8141773
TI  - Triacylglycerol metabolism by lymphocytes and the effect of triacylglycerols on
      lymphocyte proliferation.
AB  - This study investigates the ability of lymphocytes to utilize fatty acids
      originating from triacylglycerols and the effect of triacylglycerols upon mitogen
      stimulated lymphocyte proliferation. Lymphocytes isolated from rat lymph nodes,
      spleen, thymus and lymphatic duct had a lipoprotein lipase activity of approx. 10
      units/mg of protein, indicating that the fatty acids of circulating
      triacylglycerols are accessible to these cells. In culture lymph node lymphocytes
      hydrolysed triacylglycerols added to the medium as emulsions. Both non-esterified
      fatty acids and free glycerol appeared in the cell culture medium, but their
      concentrations indicated that a high proportion of each (65-90% of fatty acids
      and 60-80% of glycerol) was taken up by the cells. The incorporation and fate of
      triacylglycerol-fatty acids was studied by culturing the cells in the presence of
      tri[3H]oleoylglycerol or tri[14C]inoleoylglycerol. Both fatty acids were
      incorporated into lymphocyte lipids in a time-dependent manner; linoleic acid was
      incorporated at a significantly greater rate than oleic acid. The majority of
      oleic acid (greater than 70%) was incorporated into cellular triacylglycerol,
      while less than 10% was incorporated into phospholipids. In contrast, linoleic
      acid incorporation into cellular triacylglycerol never exceeded 25%, while up to
      45% was incorporated into phospholipids. Triacylglycerols containing
      polyunsaturated fatty acids inhibited concanavalin A-stimulated lymphocyte
      proliferation in a concentration- and time-dependent manner; triacylglycerols
      containing saturated fatty acids or oleic acid were not inhibitory. Such direct
      effects of certain triacylglycerols on lymphocyte function may explain why some
      clinical trials of polyunsaturated fatty acid-rich diets have been successful in
      improving the condition of patients suffering from inflammatory diseases.

PMID- 8141774
TI  - Transcriptional regulation of muscle fatty acid-binding protein.
AB  - Heart fatty acid-binding protein (H-FABP) is present in a wide variety of tissues
      but is found in the highest concentration in cardiac and red skeletal muscle. It
      has been proposed that the expression of H-FABP correlates directly with the
      fatty acid-oxidative capacity of the tissue. In the present study, the expression
      of H-FABP was measured in red and white skeletal muscle under two conditions in
      which fatty acid utilization is known to be increased: streptozotocin-induced
      diabetes and fasting. Protein concentration, mRNA concentration and transcription
      rate were measured under both conditions. The level of both protein and mRNA
      increased approximately 2-fold under each condition. The transcription rate was
      higher in red skeletal muscle than in white muscle, was increased 2-fold during
      fasting, but was unchanged by streptozotocin-induced diabetes. In addition to
      supporting the hypothesis that H-FABP is induced during conditions of increased
      fatty acid utilization, these findings demonstrate that the regulation of H-FABP
      expression may or may not be at the level of transcription depending on the
      stimulus.

PMID- 8141775
TI  - Production of human embryonic haemoglobin (Gower II) in a yeast expression
      system.
AB  - The cDNA coding for a human embryonic globin protein has been obtained from an
      erythroleukaemic cell line. A plasmid expression system for human embryonic
      haemoglobin Gower II containing cDNA copies of the appropriate pair of globin
      genes coupled to synthetic galactose-regulated hybrid promoters has been
      engineered. Transformation of Saccharomyces cerevisiae with this plasmid yields a
      cellular system capable of high-level production of fully functional tetrameric
      embryonic haemoglobin. We have developed a purification scheme which gives high
      yields of pure human embryonic haemoglobin suitable for structural and functional
      studies. Preliminary characterization studies are reported.

PMID- 8141776
TI  - Characterization of the antimicrobial peptide derived from sapecin B, an
      antibacterial protein of Sarcophaga peregrina (flesh fly).
AB  - Sapecin B, an antibacterial protein of Sarcophaga peregrina, was divided into
      four peptides. A hendecapeptide derived from its helix region was found to have
      comparable antibacterial activity with that of the complete protein. This peptide
      had a much wider spectrum of antimicrobial activity than that of sapecin B,
      exhibiting activity on not only Staphylococcus aureus (Gram-positive) and
      Escherichia coli (Gram-negative), but also some yeasts, including Candida
      albicans. The peptide was shown to bind to liposomes containing acidic
      phospholipids and cause release of entrapped glucose, suggesting that its primary
      site of action is the bacterial membrane. Its antimicrobial activity could be
      increased by substituting various amino acid residues for hydrophobic and/or
      basic ones.

PMID- 8141777
TI  - Presence and differential expression of SGLT1, GLUT1, GLUT2, GLUT3 and GLUT5
      hexose-transporter mRNAs in Caco-2 cell clones in relation to cell growth and
      glucose consumption.
AB  - Seven clones from the Caco-2 cell line, three isolated from passage 29 (PD7,
      PD10, PF11) and four from passage 198 (TB10, TC7, TF3, TG6), all of them selected
      on the basis of differences in the levels of expression of sucrase-isomaltase and
      rates of glucose consumption, were analysed for the expression of hexose
      transporter mRNAs (SGLT1, GLUT1-GLUT5) in relation to the phases of cell growth
      and the associated variations of the rates of glucose consumption. All clones
      showed a similar pattern of evolution of the rates of glucose consumption, which
      decreased from the exponential to the late-stationary phase, but differed, in a 1
      40-fold range, in the values observed at late postconfluency. According to these
      values, clones could be divided into high- (PD10, PF11) and low-glucose-consuming
      cells (PD7, TB10, TC7, TF3 and TG6). GLUT1 and GLUT3 mRNAs were expressed in all
      clones and showed a similar pattern of evolution: their level decreased, from the
      exponential to the stationary phase, in close correlation with the decrease in
      rates of glucose consumption, with only high-glucose-consuming clones maintaining
      high levels in the stationary phase. In contrast, SGLT1, GLUT2 and GLUT5 mRNAs
      were only expressed, like sucrase-isomaltase mRNA, in the low-glucose-consuming
      clones, and their level increased from the exponential to the stationary phase,
      in parallel with the differentiation of the cells. GLUT4 was undetectable in all
      the clones. Glucose deprivation generally resulted in a discrete decrease in the
      levels of all transporter mRNAs in all clones, one exception being GLUT2, which
      in the high-glucose-consuming clones is only detectable when the cells are grown
      in low glucose. These clones should be ideal tools with which to study in vitro,
      at the single-cell level, how these transporters concur to the utilization and
      transport of hexoses and how their exclusive or co-ordinated expression is
      regulated.

PMID- 8141778
TI  - Metabolism of aspartame by human and pig intestinal microvillar peptidases.
AB  - The artificial sweetener aspartame (N-L-alpha-aspartyl-L-phenyl-alanine-1-methyl
      ester; Nutrasweet), its decomposition product alpha Asp-Phe and the related
      peptide alpha Asp-PheNH2 were rapidly hydrolysed by microvillar membranes
      prepared from human duodenum, jejunum and ileum, and from pig duodenum and
      kidney. The metabolism of aspartame by the human and pig intestinal microvillar
      membrane preparations was inhibited significantly (> 78%) by amastatin or 1,10
      phenanthroline, and partially (> 38%) by actinonin or bestatin, and was activated
      2.9-4.5-fold by CaCl2. The inhibition by amastatin and 1,10-phenanthroline, and
      the activation by CaCl2 are characteristic of the cell-surface ectoenzyme
      aminopeptidase A (EC 3.4.11.7) and a purified preparation of this enzyme
      hydrolysed aspartame with a Km of 0.25 mM and a Vmax of 126 mumol/min per mg. A
      purified preparation of aminopeptidase W (EC 3.4.11.16) also hydrolysed aspartame
      but with a Km of 4.96 mM and a Vmax of 110 mumol/min per mg. However, rentiapril,
      an inhibitor of aminopeptidase W, caused only slight inhibition (maximally 19%)
      of the hydrolysis of aspartame by the microvillar membrane preparations. Similar
      patterns of inhibition and kinetic parameters were observed for alpha Asp-Phe and
      alpha Asp-PheNH2. Two other decomposition products of aspartame, beta Asp-PheMe
      and cyclo-Asp-Phe, were essentially resistant to hydrolysis by both the human and
      pig intestinal microvillar membrane preparations and the purified preparations of
      aminopeptidases A and W. Although the relatively selective inhibitor of
      aminopeptidase N (EC 3.4.11.2), actinonin, partially inhibited the metabolism of
      aspartame, alpha Asp-Phe and alpha Asp-PheNH2 by the human and pig intestinal
      microvillar membrane preparations, these peptides were not hydrolysed by a
      purified preparation of aminopeptidase N. Membrane dipeptidase (EC 3.4.13.19)
      only hydrolysed the unblocked dipeptide, alpha Asp-Phe, but the selective
      inhibitor of this enzyme, cilastatin, did not block the metabolism of alpha Asp
      Phe by the microvillar membrane preparations.

PMID- 8141779
TI  - Inhibition of immediate-early-gene induction in renal mesangial cells by
      depletion of intracellular polyamines.
AB  - Mitogens have been shown to stimulate the activity of the rate-limiting enzyme
      for polyamine synthesis, ornithine decarboxylase (ODC), and ODC mRNA expression
      in cultured rat mesangial cells (MCs). In addition, inhibition of ODC by alpha
      difluoromethylornithine (DFMO) results in growth arrest of MCs. To elucidate the
      mechanisms involved in the inhibition of MC proliferation due to polyamine
      depletion, we studied the effects of DFMO on the activation of phospholipase C
      and induction of the immediate early genes (IEGs), c-fos, c-jun and Egr-1, which
      are thought to regulate cell growth. Mitogenic 10% fetal-calf serum (FCS) and 1
      unit/ml thrombin activated phospholipase C in MCs within 30 s, as assessed by
      generation of [3H]inositol phosphates. This activation was not affected by DFMO.
      mRNAs of the IEGs c-fos, c-jun and Egr-1 were induced by FCS within 15 min.
      Expression of these genes reached a peak at 60 min and disappeared at 3 h.
      Treatment of MCs with a growth-suppressing dose of DFMO (5 mM) inhibited mRNAs of
      all three IEGs by 52-87% at 1 h. Total expression of Egr-1 over 20-120 min was
      diminished by 41%, and the time point of maximal expression was delayed by 40
      min. This inhibitory effect was abolished in a time-dependent manner (1-3 days)
      by prior addition of 200 microM putrescine, the reaction product of ODC. Egr-1
      mRNA expression was super-induced by the inhibitor of protein synthesis,
      cycloheximide. This effect was also blocked by DFMO. The results indicate that
      the DFMO-induced process of MC growth inhibition involves steps necessary for IEG
      activation. The signal-transduction step sensitive to polyamines occurs distal to
      the activation of phospholipase C. Since reconstitution of normal induction of
      IEGs requires 3 days, it seems likely that polyamine depletion affects the
      regulation of IEG expression in an indirect fashion. We conclude that activation
      of IEGs requires the presence of polyamines and plays a significant role in the
      induction of MC replication.

PMID- 8141780
TI  - Epidermal growth factor stimulates distinct diradylglycerol species generation in
      Swiss 3T3 fibroblasts: evidence for a potential phosphatidylcholine-specific
      phospholipase C-catalysed pathway.
AB  - Stimulation of 3T3 fibroblasts with epidermal growth factor (EGF) results in an
      increase in 1,2-diacylglycerol (DAG) mass which is maximal at 25 s, declining at
      1 min and returning to basal levels by 30 min. No changes in alkylacylglycerol or
      alkenylacylglycerol were detected. Three species account for most of this mass
      increase: 18:0/20:5,n-3, 18:0/20:4,n-6 and 18:0/20:3,n-9. These species are
      characteristic of the phosphoinositides; however, previous work failed to detect
      any EGF-stimulated rise in inositol phosphates in these cells [Cook and Wakelam
      (1992) Biochem. J. 285, 247-253]. This ruled out phosphoinositide hydrolysis by
      phospholipase C, but raised the possibility of phospholipase D/phosphatidate
      phosphohydrolase-catalysed hydrolysis of phosphatidylinositol. The inclusion of
      butanol in the incubation medium failed to block the diacylglycerol changes,
      indicating that the phospholipase D pathway is not involved and that DAG must be
      derived from another source, probably via phospholipase C-catalysed hydrolysis of
      a phosphatidylcholine pool that is particularly rich in these species. The
      tyrosine kinase inhibitor ST-271 almost abolished the elevation in 18:0/20:5,n-3,
      18:0/20:4, n-6 and 18:0/20:3,n-9 at 25 s, but only reduced the rise in total DAG
      mass by about 50%. The protein kinase C (PKC) inhibitor Ro-31-8220 increased DAG
      levels at all time points but had no effect on the species profiles. This
      provides additional evidence for PKC-mediated regulation of cell-surface EGF
      receptors, since the inhibition of PKC would increase the availability and/or
      ligand binding affinity of receptors at the plasma membrane and hence increase
      and prolong the response to EGF.

PMID- 8141781
TI  - Purification and biochemical properties of a high-molecular-mass inositol 1,4,5
      trisphosphate 3-kinase isoenzyme in human platelets.
AB  - The phosphorylation of inositol 1,4,5-trisphosphate (InsP3) to inositol 1,3,4,5
      tetrakisphosphate (InsP4) is catalysed by InsP3 3-kinase. A method is presented
      for a rapid purification of the enzyme from human platelets. The purified enzyme
      was identified as a polypeptide of M(r) 69,000-70,000 after SDS/PAGE. It had a
      specific activity of 1.45 +/- 0.1 mumol/min per mg, and the degree of stimulation
      by Ca2+/calmodulin was 17-fold at saturating calmodulin and 10 microM free Ca2+.
      The Km for InsP3 and for ATP was 2.0 microM and 2.5 mM respectively. Human
      platelet InsP3 3-kinase was not recognized by immunodetection with anti-(InsP3 3
      kinase A) or anti-(InsP3 3-kinase B) antibodies. These data provide the first
      biochemical evidence for the existence of a novel InsP3 3-kinase isoenzyme in
      human platelets, which is distinct from previously reported InsP3 3-kinase A and
      InsP3 3-kinase B.

PMID- 8141782
TI  - Nucleotide sequence of a novel arylesterase gene from Vibro mimicus and
      characterization of the enzyme expressed in Escherichia coli.
AB  - A gene coding for an arylesterase of Vibrio mimicus was cloned. Sequence
      determination reveals that the esterase gene has an open reading frame of 600
      nucleotides which encodes a protein of M(r) 22,300. The deduced amino acid
      sequence contain a pentapeptide GDSLS (residues 27-31), which was also found in
      the phospholipid-cholesterol acyltransferase from Aeromonas hydrophila.
      Substitution of Ser-29 by alanine or cysteine in the cloned gene abolished the
      esterase activity in the tributyrin plate assay. On the other hand, the activity
      was not lost when Ser-31 was changed to alanine. The cloned gene was expressed in
      Escherichia coli, and the protein purified by a four-step procedure. The purified
      protein migrated on SDS/PAGE as a single band with an apparent M(r) of 22,100.
      This enzyme favoured the hydrolysis of several arylesters and was classified as
      an arylesterase (EC 3.1.1.2). N-Terminal analysis showed that Ser-20 was the
      first amino acid of the mature secreted protein, suggesting that the N-terminal
      19 hydrophobic amino acids served as a signal peptide.

PMID- 8141783
TI  - Alkalosis- and ATP-induced increases in the diacyglycerol pool in alveolar type
      II cells are derived from phosphatidylcholine and phosphatidylinositol.
AB  - Alkalosis and ATP increase surfactant secretion in alveolar type II cells,
      possibly via non-receptor- and receptor-mediated mechanisms respectively. We
      compared the effects of these two agonists on phosphatidylinositol (PI) and 1,2
      diacylglycerol (DAG) pools and on phosphatidylcholine (PC) hydrolysis in alveolar
      type II cells. Alkalosis, caused by transfer of cells from 5% (control) to 0% CO2
      in air, and ATP increased the secretion of surfactant compared with the controls.
      The stimulated secretion was inhibited by staurosporine, a protein kinase C
      inhibitor. DAG and PI contents of control cells were 50 +/- 1.1 (mean +/- S.E.M.,
      n = 8) and 14 +/-0.8 nmol/mg phospholipid (n = 7) respectively. The DAG content
      increased by approximately 50 nmol (100%) within 5 s of treatment with both
      alkalosis and ATP, returned to control levels by 1 min, and increased again at 5
      min by approximately 20 nmol. The PI content decreased maximally by approximately
      6 nmol (40%) at 5 s and returned to control levels by 30 s with both alkalosis
      and ATP, but was unchanged thereafter. Mass-balance analysis of net changes in
      DAG and PI pools suggests that additional sources, possibly PC, must also
      contribute to the DAG increase. ATP or alkalosis also increased the hydrolysis of
      PC. The labelling of phosphocholine was increased (approximately 60%) at as early
      as 5 s and remained elevated at subsequent time points, whereas labelling of
      choline was higher only with ATP at 50 s and later, suggesting activation of
      phospholipase C by both agonists, and of phospholipase D by only ATP. Our studies
      demonstrate that ATP and alkalosis stimulate rapid hydrolysis of inositol and
      choline phospholipids to increase the DAG mass in type II cells, and that
      phospholipase C-stimulated PC hydrolysis is the major pathway for DAG formation.

PMID- 8141784
TI  - Fibrinogenolysis by a neutrophil membrane protease generates an A alpha 1-21
      fragment.
AB  - The 600 kDa neutrophil membrane neutral protease, which had been shown to
      generate bioactive peptides from the acute-phase reactant C-reactive protein, has
      now been shown to have fibrinogenolytic activity that is distinct from
      fibrinogenolysis by plasmin and neutrophil lysosomal enzymes. This protease
      gradually reduces the apparent molecular mass of fibrinogen (340 kDa) to non
      clottable products and generates terminal products with apparent molecular mass
      values of 270 kDa, 200 kDa, 100 kDa and less than 40 kDa through cleavage of all
      three of the constituent chains. Characteristics of fibrinogenolysis by this
      neutrophil protease are cleavage of the bond between amino acids valine and
      glutamic acid at positions 21 and 22 respectively from the N-terminus of the A
      alpha chain to release an A alpha 1-21 peptide, digestion of the B beta chain at
      positions within the C-terminus, and proteolysis of the bond between amino acids
      isoleucine and glycine at positions 394 and 395 respectively from the N-terminus
      of the gamma chain. This generates products that lack anticoagulant activity. The
      thrombin clotting time of the product with an apparent molecular mass of 330 kDa
      was prolonged, although clot formation was still observed. Loss of coagulability
      and inability to clot was found with further degradation of fibrinogen to an
      apparent molecular mass of 290 kDa. Activity of this neutrophil membrane protease
      in vivo could be important for the regulation of fibrin deposition at sites of
      inflammation, and may contribute to the reported plasma levels of the A alpha 1
      21 peptide.

PMID- 8141785
TI  - Cytodifferentiation in Tetrahymena vorax is linked to glycosyl
      phosphatidylinositol-anchored protein assembly.
AB  - The role of glycosyl-PtdIns (GPI)-anchored proteins in the cytodifferentiation of
      Tetrahymena vorax was examined. Labelling of cells with [3H]myristate or
      [3H]palmitate followed by electrophoresis showed an array of proteins carrying
      covalently bound lipids. Electrophoresis of protein from cells labelled with the
      GPI-anchor components [3H]Ins and [14C]ethanolamine revealed three polypeptides
      on fluorograms which have apparent molecular masses of approx. 28, 50 and 82 kDa.
      Labelled lipid associated with these polypeptides was susceptible to release by
      in vitro exposure to Bacillus thuringiensis PtdIns-specific phospholipase C (PI
      PLC). Using labelled fatty acids, cells induced to differentiate showed altered
      GPI-anchored protein-labelling patterns in comparison with undifferentiated
      control cells, with a heavily labelled 32 kDa band appearing upon
      differentiation. Pre-incubation of cells in 10 mM D-mannosamine, an inhibitor of
      GPI incorporation into protein, resulted in a reduction of the incorporation of
      label into the three GPI-anchored proteins, nearly complete inhibition of
      differentiation and a reduction in the rate of digestive vacuole formation. A 50%
      inhibition of differentiation was obtained using 500 microM mannosamine. The
      inhibitory impact of D-mannosamine on differentiation could be competitively and
      completely reversed by the inclusion of D-mannose, but not D-glucose. Neither
      glucosamine nor tunicamycin inhibited differentiation. Incubation of cells in PI
      PLC (5 units/ml) plus the differentiation inducer resulted in an acceleration of
      differentiation and generally higher percentages of differentiated cells versus
      controls.

PMID- 8141786
TI  - Cellulose hydrolysis by the cellulases from Trichoderma reesei: a new model for
      synergistic interaction.
AB  - The hydrolysis of Whatman no. 1 filter paper by purified cellulolytic components
      from Trichoderma reesei and the synergistic action of binary combinations of
      these enzymes on the same substrate were investigated. At 20 milligrams filter
      paper, enzyme concentrations needed to obtain half-maximal hydrolysis rates (KE
      values) were in the 3-4 microM range for the cellobiohydrolases (CBHs) and 0.05
      0.10 microM for the endoglucanases (EGs). Catalytic-core proteins of CBH I and EG
      III, lacking the cellulose-binding domain, exhibit KE values 2.3 and 5.1 times
      higher than those of the intact enzymes. In synergistic combinations of two
      cellulases, the KE value of at least one enzyme was 3-10-fold reduced. CBH I/CBH
      II and CBH I/EG III combinations showed the most powerful synergism, and optimal
      ratios were a function of the total protein concentration. Results obtained in
      activity and adsorption assays using filter paper pretreated with one component,
      followed by inactivation and subsequent hydrolysis with the same or another
      cellulase component, point to a sequential enzymic attack of the cellulose and
      seems consistent with the mathematical model presented.

PMID- 8141787
TI  - The region around residue 115 of human bactericidal/permeability-increasing
      protein is not involved in lipopolysaccharide binding or bactericidal activity.
      Chemical synthesis and expression of a gene coding for the active domain and
      characterization of recombinant proteins.
AB  - Bactericidal/permeability-increasing protein (BPI) is a potent antimicrobial
      agent produced by polymorphonuclear leucocytes that specifically interacts with
      and kills Gram-negative bacteria. An 825 bp gene determining the bactericidal N
      terminal domain of human BPI was chemically synthesized and expressed as
      inclusion bodies in Escherichia coli. The recombinant polypeptide, BPI', was
      solubilized and conditions under which it folded to give the active protein were
      determined. Folding was critically dependent on the urea and salt concentrations
      as well as the pH. BPI' bound with high affinity to Salmonella typhimurium cells
      (apparent Kd = 36 nM), permeabilized their outer membranes to actinomycin D,
      specifically activated a synovial fluid phospholipase A2 and showed potent
      bactericidal activity. In contrast with the native protein, however, it could not
      be efficiently released from the cell surface by the addition of high
      concentrations of Mg2+ ions. Pre-incubation of the protein with
      lipopolysaccharide or trypsin prevented cytotoxicity. However, boiling BPI'
      immediately before its addition to cells did not block its bactericidal activity,
      suggesting that it may be able to function even when presented to cells in an
      unfolded form. A BPI' derivative, containing a 13-residue foreign antigenic
      determinant genetically inserted between Ala115 and Asp116, was also produced.
      The derivative was functional in the above assays and bound with high affinity to
      S. typhimurium (apparent Kd = 74 nM). These results imply that the region defined
      by these residues is not involved in the lipopolysaccharide-binding or
      bactericidal activities of BPI. The availability of functional, nonglycosylated
      recombinant derivatives of BPI should greatly aid detailed studies on its
      structure, interactions with lipopolysaccharide and mechanism of action.

PMID- 8141788
TI  - Periplasmic expression of human interferon-alpha 2c in Escherichia coli results
      in a correctly folded molecule.
AB  - Human interferon-alpha 2c (IFN-alpha 2c) was produced in Escherichia coli under
      the control of the alkaline phosphatase promoter using a periplasmic expression
      system. Compared with other leader sequences, the heat-stable enterotoxin II
      leader of E. coli (STII) resulted in the highest rate of correct processing as
      judged by Western-blot analysis. The fermentation was designed as a batch-fed
      process in order to obtain a high yield of biomass. The processing rate of IFN
      alpha 2c could be increased from 25% to more than 50% by shifting the
      fermentation pH from 7.0 to 6.7. IFN-alpha 2c extracted from the periplasm was
      purified by a new four-step chromatographic procedure. Whereas cytoplasmically
      produced IFN-alpha 2c does not have its full native structure, IFN-alpha 2c
      extracted from the periplasm was found to be correctly folded, as shown by c.d.
      spectroscopy. Peptide-map analysis in combination with m.s. revealed the correct
      formation of disulphide bridges. N-terminal sequence analysis showed complete
      removal of the leader sequence, creating the authentic N-terminus starting with
      cysteine.

PMID- 8141789
TI  - Component analysis and characterization of a nuclear deoxyribonucleotidase.
AB  - We have previously reported the identification of a novel activity residing in
      the nuclear fraction of mammalian cells that selectively binds and hydrolyses
      deoxyribonucleoside triphosphates. Incubation of this protein with [alpha
      32P]dATP leads to the appearance of a retarded band relative to free dATP when
      the reaction is analysed on non-denaturing polyacrylamide gels. We now show that
      the retarded species comprises the product of dATP hydrolysis (dADP or dAMP)
      bound to an as yet unidentified species. We have termed this complex the 'product
      nucleotide binding particle' or PNBP*. Through a combination of continuous
      elution polyacrylamide-gel electrophoresis and gel-filtration chromatography, we
      demonstrate that the hydrolytic activity (dNTPase) is distinct from the
      radiolabelled species detected in gel-retardation experiments. T.l.c. confirms
      that the labelled product does not share RF values associated with a range of
      mono-, di- and tri-phosphate deoxyribonucleotide standards, and gel-filtration
      experiments suggest a molecular mass for PNBP* of between 2.5 and 3 kDa. The
      ability of purified PNBP* to retain its nucleotide ligand after a number of
      denaturing processes suggests that the ligand is covalently bound. The recovery
      of dNTPase activity from both gel-filtration and ion-exchange chromatography
      reveals that the as yet unliganded PNBP* (or a precursor form) is associated with
      the dNTPase enzyme as part of the active complex, prior to addition of dATP.

PMID- 8141791
TI  - Specific binding sites for inositol 1,3,4,5-tetrakisphosphate are located
      predominantly in the plasma membranes of human platelets.
AB  - In the present study we describe the characterization and localization of
      Ins(1,3,4,5)P4-binding sites in human platelet membranes. Specific binding sites
      for Ins(1,3,4,5)P4 have been identified on mixed, plasma and intracellular
      membranes from neuraminidase-treated platelets using highly purified carrier-free
      [32P]Ins(1,3,4,5)P4. The displacement of Ins(1,3,4,5)P4 from these sites by
      Ins(1,4,5)P3 and InsP6 occurs at greater than two orders of magnitude higher
      concentrations and with Ins(1,3,4,5,6)P5 at about 40-fold higher concentrations
      than with Ins(1,3,4,5)P4. The membranes were further separated by free-flow
      electrophoresis into plasma and intracellular membranes. The Ins(1,3,4,5)P4
      binding sites separated with plasma membranes, and showed similar affinities and
      specificities as mixed membranes, whereas Ins(1,4,5)P3-binding sites were
      predominantly in the intracellular membranes. These results suggest a
      predominantly plasma membrane location for putative Ins(1,3,4,5)P4 receptors in
      human platelets.

PMID- 8141790
TI  - Ceramide does not mediate the effect of tumour necrosis factor alpha on
      superoxide generation in human neutrophils.
AB  - The effect of tumour necrosis factor alpha (TNF alpha) on superoxide generation
      in human neutrophils was investigated using the Nitro Blue Tetrazolium reduction
      assay. TNF alpha stimulated superoxide generation in a time- and concentration
      dependent fashion. The maximally effective concentration of TNF alpha for
      superoxide generation was 10 nM and maximal response was obtained after 15-20
      min. The monoclonal antibody (mAb), utr-1, which was raised against the 75 kDa
      receptor and behaves as an antagonist, had no effect on superoxide generation,
      but partially inhibited the response to TNF alpha. mAb htr-9, which was raised
      against the 55 kDa receptor and behaves as an agonist, mimicked the effect of TNF
      alpha, but with a lower maximal response. As it has been reported that ceramide
      might act as a second messenger to mediate many of the effects of TNF alpha, the
      effects of exogenous sphingomyelinase and the cell-permeable ceramide analogue,
      C2- ceramide, on production of superoxide anions, induction of priming in
      response to formylmethionyl-leucyl-phenylalanine, and cell-shape change were
      examined. Neither sphingomyelinase nor C2-ceramide mimicked the effect of TNF
      alpha. Ceramide is converted into ceramide 1-phosphate by ceramide kinase and we
      have measured levels of this metabolite to clarify the effect of TNF alpha on
      sphingomyelinase activity in neutrophils. Although exogenous sphingomyelinase
      increased the amount of ceramide 1-phosphate in a time-dependent manner, and C2
      ceramide was rapidly converted into C2-ceramide phosphate, TNF alpha had no
      effect on the level of ceramide 1-phosphate. These results suggest that TNF alpha
      stimulates superoxide generation through both the 55 kDa and 75 kDa receptors,
      but that ceramide does not act as an intracellular mediator for TNF alpha in
      human neutrophils.

PMID- 8141792
TI  - Transmembrane orientation of the N-terminal and C-terminal ends of the ryanodine
      receptor in the sarcoplasmic reticulum of rabbit skeletal muscle.
AB  - Antibodies were raised against synthetic peptides corresponding to the N-terminal
      (residues 2-15) and the C-terminal (residues 5027-5037) parts of the rabbit
      skeletal muscle ryanodine receptor. The specificity of the antibodies generated
      was tested by e.l.i.s.a., Western blotting and immunofluorescence. All these
      tests demonstrated the specificity of the antibodies and their ability to react
      with both the native and the denaturated ryanodine receptor. Both the anti-N
      terminus and the anti-C-terminus antibodies bound to sarcoplasmic reticulum
      vesicles, indicating that each end of the membrane-embedded ryanodine receptor is
      exposed to the cytoplasmic side of the vesicles. These immunological data were
      complemented with proteolysis experiments using carboxypeptidase A.
      Carboxypeptidase A induced degradation of the C-terminal end of the ryanodine
      receptor in sarcoplasmic reticulum vesicles and a concomitant loss of reactivity
      of the anti-C-terminus antibodies in Western blots, providing extra evidence for
      the cytoplasmic localization of the C-terminal end of the ryanodine receptor.

PMID- 8141793
TI  - Purification and some characteristics of the acetylxylan esterase from
      Schizophyllum commune.
AB  - Acetylxylan esterase from Schizophyllum commune was purified using ion-exchange
      and hydrophobic chromatography. The enzyme has a molecular mass of 31 kDa, as
      determined by SDS/PAGE, or 18 kDa, according to gel filtration. Glycosylation of
      the enzyme was not detected. Acetylxylan esterase is relatively stable under
      laboratory conditions; it retains full activity at pH 6.2-8.5 upon incubation at
      25 degrees C for 7 h, but loses nearly the whole activity upon incubation at 60
      degrees C for 30 min. The pH optimum of the enzyme activity is 7.7 and its
      temperature optimum lies between 30 and 45 degrees C. Ca2+ and Co2+ inhibit
      markedly the activity of acetylxylan esterase at a concentration of 10 mM, as do
      Mn2+, Zn2+, Fe2+ and Cu2+ at a concentration of 1 mM.

PMID- 8141794
TI  - Additional isoforms of multifunctional calcium/calmodulin-dependent protein
      kinase II in rat heart tissue.

PMID- 8141795
TI  - Feedback controls and G2 checkpoints: fission yeast as a model system.
AB  - Dependency relationships within the cell cycle allow cells to arrest the cycle
      reversibly in response to agents or conditions that interfere with specific
      aspects of its normal progression. In addition, overlapping pathways exist which
      also arrest the cell cycle in response to DNA damage. Collectively, these control
      mechanisms have become known as checkpoints. Analysis of checkpoints is
      facilitated by the fact that dependency relationships within the cell cycle, such
      as the dependency of mitosis on the completion of DNA synthesis, and the DNA
      damage checkpoint can be separated genetically. In fission yeast,
      Schizosaccharomyces pombe, the dependency of mitosis on prior completion of DNA
      synthesis is mediated through tyrosine-15 phosphorylation of the ubiquitous
      mitotic regulator p34cdc2. In contrast, the arrest of mitosis caused by DNA
      damage acts through a separate mechanism that appears to be independent of
      tyrosine-15 phosphorylation. Despite these distinct interactions with the mitotic
      machinery, the majority of fission yeast mutants that are deficient in mitotic
      arrest after DNA damage are also unable to respond to inhibition of DNA
      synthesis. In this essay we survey the current knowledge concerning feedback
      controls and checkpoints within fission yeast and relate this to information
      derived from other systems.

PMID- 8141796
TI  - Dogs, distemper and Paget's disease.
AB  - The cause of Paget's disease is still unknown, despite many years of intensive
      study. During this time, evidence has sporadically emerged to suggest that the
      disease may result from a slow viral infection by one or more of the
      Paramyxoviruses. More recently, epidemiologic and molecular studies have
      suggested that the canine paramyxovirus, canine distemper virus, is the virus
      responsible for the disease. If true, then along with rabies, this would be a
      further example of a canine virus causing human disease. Studies in the natural
      host have now supported these findings. Further investigations have proposed that
      the bony abnormalities seen in Paget's disease are due to the effects of the
      virus on osteoclastic interleukin-6 and c-FOS production, possibly via the
      transcription factor NF-kappa B.

PMID- 8141797
TI  - Chemosensory regulation of development in C. elegans.
AB  - The dauer larva is a specialized third-larval stage of Caenorhabditis elegans
      that is long-lived and resistant to environmental insult. The dauer larva is
      formed in response to a high external concentration of a constitutively secreted
      pheromone. Response to the dauer-inducing pheromone of C. elegans is a promising
      genetic model for metazoan chemosensory transduction. More than 20 genes have
      been identified that are required for normal pheromone response. The functions of
      these genes include production of the pheromone, exposure of sensory neuron
      endings to the environment, structural and functional integrity of those sensory
      endings, and the capacity of sensory neurons to make appropriate output. Genetic
      evidence suggests that two partially redundant sensory pathways act in concert to
      control dauer formation. At least two classes of chemosensory neurons, ADF and
      ASI, are implicated in the pheromone response. On the basis of on these findings,
      a speculative model for the pheromone response is proposed. In this model, the
      neurons ADF and ASI are pheromone sensors that repress dauer formation in the
      absence of pheromone and derepress dauer formation in response to pheromone. It
      is currently unclear whether or not the two genetically defined sensory pathways
      both act in ADF and ASI.

PMID- 8141798
TI  - The secretion pathway of IgA protease-type proteins in gram-negative bacteria.
AB  - The pathogenic, Gram-negative bacteria, Neisseria gonorrhoeae, Neisseria
      meningitidis and Haemophilus influenzae, secrete immunoglobulin A1 proteases into
      their extracellular surroundings. An extraordinary feature in the secretory
      pathway of these putative virulence factors is a self-directed outer membrane
      transport step allowing the proteins to be secreted autonomously, even from
      foreign Gram-negative host cells like Escherichia coli. Here we summarize recent
      achievements in the understanding of IgA protease outer membrane translocation.

PMID- 8141799
TI  - Contact inhibition in the failure of mammalian CNS axonal regeneration.
AB  - Anamniote animals, such as fish and amphibians, are able to regenerate damaged
      CNS nerves following injury, but regeneration in the mammalian CNS tracts, such
      as the optic nerve, does not occur. However, severed adult mammalian retinal
      axons can regenerate into peripheral nerve segments grafted into the brain and
      this finding has emphasized the importance of the environment in explaining
      regenerative failure in the adult mammalian CNS. Following lesions, regenerating
      axons encounter the glial cells, oligodendrocytes and astrocytes, and their
      derivatives, respectively myelin and the astrocytic scar. Experiments to
      investigate the influence of these components on axon growth in culture have
      revealed cell-surface and extracellular matrix molecules that inhibit axon
      extension and growth cone motility. Structural and functional characterization of
      these ligands and their receptors is underway, and may solve the interesting
      neurobiological conundrum posed by the failure of mammalian CNS regeneration.
      Simultaneously, this might allow new possibilities for treatment of the severe
      clinical disabilities resulting from injury to the brain and spinal cord.

PMID- 8141800
TI  - X chromosome inactivation: the feminine mystique continues.

PMID- 8141801
TI  - Defining a neural 'ground state' and photoreceptor cell identifies in the
      Drosophila eye.

PMID- 8141802
TI  - High-frequency induction of chromosomal rearrangements in mouse germ cells by the
      chemotherapeutic agent chlorambucil.
AB  - Recent mutagenesis studies have demonstrated that the chemotherapeutic agent,
      chlorambucil (CHL), is highly mutagenic in male germ cells of the mouse. Post
      meiotic germ cells, and especially early spermatids, are the most sensitive to
      the cytotoxic and mutagenic effects of this agent. Genetic, cytogenetic and
      molecular analyses of many induced mutations have shown that, in these germ-cell
      stages, CHL induces predominantly chromosomal rearrangements (deletions and
      translocations), and mutation-rate studies show that, in terms of tolerated
      doses, CHL is perhaps five to ten times more efficient in inducing rearrangements
      than is radiation exposure. Appropriate breeding protocols, along with knowledge
      of the advantages and limitations associated with the use of CHL, can be used to
      expand the current resource of chromosomal rearrangements in the mouse and to
      provide new phenotype-associated mutations amenable to positional-cloning
      techniques. The analysis of CHL-induced mutations has also contributed to
      understanding the factors that affect the yield and nature of chemically induced
      germline mutations in mammals.

PMID- 8141803
TI  - The penicillin method of mutant selection.

PMID- 8141804
TI  - DNA helicases: enzymes with essential roles in all aspects of DNA metabolism.
AB  - DNA helicases catalyze the disruption of the hydrogen bonds that hold the two
      strands of double-stranded DNA together. This energy-requiring unwinding reaction
      results in the formation of the single-stranded DNA required as a template or
      reaction intermediate in DNA replication, repair and recombination. A combination
      of biochemical and genetic studies have been used to probe and define the roles
      of the multiple DNA helicases found in E. coli. This work and similar efforts in
      eukaryotic cells, although far from complete, have established that DNA helicases
      are essential components of the machinery that interacts with the DNA molecule.

PMID- 8141805
TI  - Radical solutions and cultural problems: could free oxygen radicals be
      responsible for the impaired development of preimplantation mammalian embryos in
      vitro?
AB  - A major obstacle to the study of mammalian development, and to the practical
      application of knowledge gained from it in the clinic during therapeutic in vitro
      fertilisation and embryo transfer (IVF-ET), is the propensity of embryos to
      become retarded or arrested during their culture in vitro. The precise
      developmental cell cycle in which embryos arrest or delay is characteristic for
      the species and coincides with the earliest period of embryonic gene expression.
      Much evidence reviewed here implicates free oxygen radicals (FORs) in the process
      of arrest. Thus, studies on the development of mouse preimplantation embryos in
      vitro have shown that (i) FORs are elevated in vitro, but not in vivo, at the
      time at which embryos become arrested or delayed, (ii) systems for removing
      reactive oxygen species to limit the formation of hydroxy radicals are present,
      although they have not yet been assessed quantitatively and may differ
      qualitatively from those in adult cells, (iii) metabolic and possibly genetic
      adaptations to oxidative damage are evident, (iv) published procedures for
      overcoming in vitro arrest are explicable in terms of FOR-mediated damage or
      responses and (v) the arrest or delay of most embryos in vitro can be reduced or
      prevented experimentally by addition of metal chelators to limit hydroxy radical
      formation and lipid hydroperoxidation.

PMID- 8141806
TI  - Biological actions of IGFs in mammalian development.

PMID- 8141807
TI  - Unusual DNA structures, chromatin and transcription.
AB  - Extensive studies of DNA secondary structure during the past decade have shown
      that DNA is a dynamic molecule, whose structure depends on the underlying
      nucleotide sequence and is influenced by the environment and the overall DNA
      topology. Three major non-B-DNA structures have been described (Z-DNA, triplex
      DNA and cruciform DNA) which are stabilized by unconstrained negative
      supercoiling and can be formed under physiological conditions. In this essay we
      summarize the DNA primary structure features that are pertinent to the formation
      of these conformers and present data concerning the occurrence of these sequences
      in the eukaryotic genome. The evidence in favor of the existence of these unusual
      DNA structures in vivo is discussed. The effect of alternative non-B-DNA
      structures on the way DNA is organized in chromatin is considered, and this is
      followed by evaluation of the data relating these structures to eukaryotic
      transcription. Some possible mechanisms by which the effect of non-B structures
      on transcription might be exerted are proposed.

PMID- 8141808
TI  - Cell cycle checkpoints, DNA repair and DNA replication strategies.

PMID- 8141810
TI  - DNA single strand breaks in peripheral human lymphocytes after anesthesia with
      isoflurane-nitrous oxide-oxygen.
AB  - DNA single strand breaks were determined in peripheral lymphocytes of
      neurosurgical patients before and after 180 min of general anesthesia with
      isoflurane (CAS 26675-46-7)-nitrous oxide-oxygen. Immediately after anesthesia,
      the frequency of DNA single strand-breaks appeared to be significantly enhanced.
      In the majority of patients the DNA single strand breaks induced was equivalent
      to the effect of 0.2-0.5 Gray following x-ray radiation of lymphocytes in vitro.
      In a part of the examined patients these investigations were repeated on the
      first postoperative day. Then an increase of the frequency of DNA single strand
      breaks could not be demonstrated any more. The DNA single strand breaks were
      repaired by cellular repair systems. As DNA repair is regulated genetically,
      isoflurane-nitrous oxide-oxygen could induce DNA damage in patients with DNA
      repair defects.

PMID- 8141809
TI  - Evaluation of the mutagenicity of a-dihydroergocryptine in vitro and in vivo.
AB  - The mutagenic potential of the ergot alkaloid a-dihydroergocryptine (a-DEC, CAS
      14271-05-7) was assessed in a series of 5 assays designed to measure gene
      mutation, chromosomal damage and primary DNA damage. All tests were carried out
      in accordance with appropriate EEC and OECD Guidelines. No indications of
      mutagenic potential were observed in any of the assays.

PMID- 8141811
TI  - Effect of amrinone and milrinone on myocardial ischemia extent and infarct size
      in isolated rabbit hearts.
AB  - The effect of inotropics on myocardial ischemia is difficult to predict, since
      inotropics may influence the determinants of myocardial O2-demand and O2-supply
      differently. Several phosphodiesterase-inhibitors have been reported to possess
      antiischemic properties related in vivo to their hemodynamic and O2-sparing
      effects. The effects of amrinone (CAS 60719-84-8) (10(-6) mol/l or 5 x 10(-5)
      mol/l) or milrinone (CAS 78415-72-2) 10(-5) mol/l) on myocardial ischemia extent
      and infarct size were compared in isolated electrically paced rabbit hearts
      (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l).
      Myocardial ischemia was induced by left coronary artery branch occlusion and
      quantitated from epicardial NADH-fluorescence photography. Infarct size was
      determined by Evan's blue dye and nitroblue-tetrazolium staining and planimetry.
      At low concentration (10(-6) mol/l), amrinone had no significant influence on
      left ventricular pressure or coronary flow (p < 0.05) and epicardial NADH
      fluorescence area or infarct size were not significantly affected compared to
      controls (p > 0.05). Amrinone (5 x 10(-5) mol/l) or milrinone (10(-5) mol/l)
      significantly increased left ventricular pressure (+10%, p < 0.05) and coronary
      flow (+30, 40%, p < 0.05) to a similar extent. Concomitantly, both agents
      similarly reduced epicardial NADH-fluorescence area (-25%, p < 0.05) and infarct
      size relative to the area at risk or ventricle size compared to controls (p <
      0.05). CONCLUSION: amrinone or milrinone possess comparable antiischemic effects
      in isolated rabbit hearts that seem to be related to coronary dilator activity of
      these agents.

PMID- 8141812
TI  - Effects of the new long-acting dihydropyridine calcium antagonist pranidipine on
      the endothelium-dependent relaxation in isolated rat aorta in vitro.
AB  - The action of methyl 3-phenyl-2 (E)-propenyl 1,4-dihydro-2,6-dimethyl- 4-(3
      nitrophenyl)-3,5-pyridinedicarboxylate (pranidipine, OPC-13340, CAS 99522-79-9)
      on the endothelium-dependent relaxation in the isolated aorta in vitro was
      examined in comparison with other calcium antagonists (nifedipine, nitrendipine,
      nicardipine, diltiazem and verapamil). In the isolated aortic preparation of
      Wistar rats, acetylcholine (10(-5) mol/l), ATP (10(-5) mol/l or histamine (10(-5)
      10(-4) mol/l) caused endothelium-dependent relaxation when the strips were
      previously contracted with prostaglandin F2 alpha. This endothelium-dependent
      relaxation recovered within a few minutes, although the mechanisms of this
      contraction after relaxation were not clear. The pretreatment with pranidipine
      for 20 min extended the duration of the endothelium-dependent relaxation,
      however, there was no potentiation in magnitude of the relaxation. This effect on
      the duration of endothelium-dependent relaxation was prominent in pranidipine,
      namely, other calcium antagonists tested had not this action at clinical
      concentrations. This phenomenon was also observed when the strips were pre
      contracted with norepinephrine. This action of pranidipine might be some
      beneficial feature for therapeutic use of the compound.

PMID- 8141813
TI  - Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 1st
      communication: comparative studies on the cardiovascular effects of methyl-4,7
      dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2,3- b]pyridine-5-carboxylate
      and its two enantiomers in experimental animals.
AB  - Antihypertensive effects in conscious spontaneously hypertensive rats (SHR),
      cardiovascular effects in anesthetized dogs, and calcium antagonistic effects in
      the rabbit isolated basilar arteries and guinea-pig isolated coronary arteries of
      S-312 (methyl-4,7-dihydro-3-isobutyl-6-methyl-4- (3-nitrophenyl) thieno [2,3-b]
      pyridine-5-carboxylate) and its two enantiomers were comparatively investigated.
      The antihypertensive effect in SHR and hypotensive effect in anesthetized dogs of
      S-312-d (CAS 120056-57-7) were approximately 2 times more potent than those of S
      312, but these effects of S-312-l were very weak even at 10 to 100 times higher
      doses. Increases of vertebral blood flow in dogs with S-312 and S-312-d were
      almost corresponding. The IC50 concentrations of S-312-d, S-312, S-312-l in the
      rabbit isolated basilar arteries contracted with high K+ solution were 1.4 x 10(
      10) mol/l, 2.2 x 10(-10) mol/l, and 4.6 x 10(-9) mol/l, respectively. The
      relaxing effect of S-312-d in the isolated coronary arteries was most potent,
      followed by those of S-312 and S-312-l. It is concluded that the cardiovascular
      and calcium antagonistic effect of S-312-d are mainly responsible for those
      effects of S-312.

PMID- 8141814
TI  - Pharmacological studies on a new Dihydrothienopyridine calcium antagonist. 2nd
      communication: effects of S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4- (3
      nitrophenyl)thieno[2,3-b]pyridine-5-carboxylate on the 1,4-dihydropyridine
      binding sites in the brain and on isolated arteries in the Cynomolgus monkey.
AB  - The effects of S-312-d (S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-
      nitrophenyl)thieno[2,3-b]pyridine-5-carboxylate, CAS 120056-57-7) on the 1,4
      dihydropyridine binding sites using membrane fractions prepared from monkey
      cerebral cortex, hippocampus, and cerebellum and on isolated monkey arteries were
      investigated. Specific binding of [3H]-(+)-isradipine was saturable and
      reversible, and of high affinity. 1,4-Dihydropyridine calcium channel antagonists
      competed for the binding in the order of S-312-d = nilvadipine = nicardipine >
      nifedipine. The effect of S-312-d on the binding was due mainly to alterations in
      the dissociation constant (Kd), without alterations in the binding density
      (Bmax). In the helical strips of cerebral, coronary, renal mesenteric, and
      femoral arteries contracted with K+ or prostaglandin (PG) F2 alpha, the addition
      of S-312-d caused a concentration-dependent relaxation. Relaxant activities of S
      312-d in the cerebral arteries contracted with U-46619 (a thromboxane A2 mimetic)
      or endothelin-1 did not differ significantly from those in the arteries
      contracted with K+ or PGF2 alpha. Potencies of relaxations induced by S-312-d and
      1,4-dihydropyridine calcium channel antagonists in the K(+)-depolarized
      mesenteric arteries correlated well with those of the binding experiment. Ca(2+)
      induced contractions in the mesenteric arteries previously exposed to Ca(2+)-free
      medium and depolarized by excess K+ were attenuated by S-312-d, whereas PGF2
      alpha-induced contractions of the arteries exposed to Ca(2+)-free medium were
      unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141815
TI  - Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 3rd
      communication: antihypertensive effects of S-(+)-methyl-4,7-dihydro-3-isobutyl-6
      methyl-4-(3-nitrophenyl)thieno[2, 3-b] pyridine-5-carboxylate in hypertensive
      rats and dogs.
AB  - Hypotensive and antihypertensive effects of S-312-d (S-(+)-methyl-4,7-dihydro-3
      isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate, CAS
      120056-57-7) in Wistar Kyoto rat (WKY), spontaneously hypertensive rat (SHR),
      stroke-prone SHR (SHRSP), and DOCA-salt hypertensive rat (DOCA-HR) were compared
      with those of other representative calcium antagonists. The minimal effective
      hypotensive dose of S-312-d in WKY was 3 mg/kg p.o. and those in SHR, SHRSP, and
      DOCA-HR were 1 mg/kg p.o. in gum arabic suspension. The minimal antihypertensive
      dose of S-312-d in polyethylene glycol solution was 0.3 mg/kg p.o. in SHRSP. The
      antihypertensive effects of S-312-d was the most potent and long-lasting compared
      with the calcium antagonists, nifedipine, nicardipine, nimodipine, nilvadipine,
      and flunarizine. In conscious two-kidney Goldblatt-type hypertensive dogs, a
      significant antihypertensive effect and concomitant increases of heart rate with
      S-312-d at 1 mg/kg lasted for 4 to 6 h after oral administration. Determination
      of the plasma concentration of S-312-d by HPLC showed that more than 4.3 ng/ml of
      S-312-d is required for a significant antihypertensive effect. Subcutaneous
      administration of atenolol at 20 mg/kg 30 min before S-312-d significantly
      inhibited the tachycardia with S-312-d at 1 mg/kg p.o. but not its
      antihypertensive effect. S-312-d is considered useful for the treatment of
      essential hypertension and related organ disorders.

PMID- 8141816
TI  - Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 4th
      communication: prophylactic and therapeutic effects of S-(+)-methyl-4,7-dihydro-3
      isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate in
      stroke-prone spontaneously hypertensive rats.
AB  - The prophylactic and therapeutic effects of S-312-d (S-(+)-methyl-4,7-dihydro-3
      isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate, CAS
      120056-57-7) were compared with those of nimodipine or nicardipine using male
      stroke-prone spontaneously hypertensive rats (SHRSP). The survival rate of SHRSP
      was dose-dependently increased by once a day oral administration of S-312-d (0.3,
      1, and 3 mg/kg) or nimodipine (10 mg/kg), while all non-treated SHRSP fed with
      high Na+ diet died within 40 days after the start of the experiment. All SHRSP
      treated with 3 mg/kg S-312-d survived during the 60-day experiment periods.
      Marked decreases of body weights and various neurological symptoms were also
      inhibited with S-312-d or nimodipine. Moderate diuretic effects were observed
      with S-312-d at doses of 1 and 3 mg/kg. The appearance of urinary occult blood in
      control SHRSP was markedly inhibited with S-312-d at 1 mg/kg and nimodipine at 10
      mg/kg. Histological examination of the brain of SHRSP showed that cerebral stroke
      lesion including edema, hemorrhage, and/or softening was dose-dependently
      inhibited with S-312-d. Once a day oral administration of S-312-d (1, 3, or 10
      mg/kg) dose-dependently increased the body weights and improved the neurological
      symptoms of diseased SHRSP. The appearance of proteinuria and of occult blood in
      the urine of SHRSP were also markedly inhibited with S-312-d or nicardipine.
      Histological examination of the brain of SHRSP showed that the arbitrary
      neurotoxic index (ANI) for stroke lesion dose-dependently decreased with S-312-d
      at 1, 3, and 10 mg/kg as follows: 4.8, 3.0, 2.3. The ANI for non-treated SHRSP
      was 7.6. The therapeutic effects of nicardipine (ANI 3.9) at 10 mg/kg
      corresponded to those of S-312-d at 3 mg/kg. Thus, S-312-d can be recommended for
      the treatment of cerebral insufficiency or vasospasm following stroke as well as
      in essential hypertension.

PMID- 8141818
TI  - Influence of clonidine on the porphyrin metabolism in female rats.
AB  - Effects of different doses of clonidine (CAS 4205-90-7) (15, 150, or 300
      micrograms/kg body weight) over a period of 3, 14, or 64 days on the activities
      of delta-aminolevulinic acid synthase (ALA-S) and the P450 dependent isoenzymes
      aminopyrine-N-demethylase (ADM), 7-ethoxycoumarin-O-deethylase (7-ECO-D), and 7
      ethoxyresorufin-O-deethylase (7-ERO-D) as well as on the hepatic porphyrin and
      P450 content were studied in female rats. Additionally, the urinary excretion of
      total porphyrins, and porphyrin precursors delta-aminolevulinic acid (ALA) and
      porphobilinogen (PBG) and the plasma clonidine level were measured. No changes in
      the activity of ALA-S and in the hepatic and urinary porphyrin, ALA and PBG
      contents were observed. An increase in the activities of ADM in the short and
      median term application of clonidine and of 7-ERO-D in the long term application
      was detected. It is concluded from these findings that clonidine has no effect on
      the porphyrin biosynthesis, but has an influence on the activities of P450
      dependent isoenzymes ADM or 7-ERO-D.

PMID- 8141817
TI  - Effects of the new calcium antagonist monatepil on cardiac function and
      myocardial oxygen supply and demand in animals.
AB  - The effects of monatepil ([(+/-)-N-(6,11-dihydrodibenzo[b,e]thiepin-11-yl)-4-(p
      fluor ophenyl)-1- piperazinebutyramide]maleate, AJ-2615, CAS 103377-41-9), a new
      calcium antagonist, on cardiac function and myocardial oxygen supply and demand
      were examined. 1. Monatepil reduced the spontaneous beats of isolated rabbit
      atria at the concentration of 3 x 10(-6) and 10(-5) mol/l. Monatepil decreased
      the contractile force of papillary muscles in a concentration-dependent manner (3
      x 10(-8)-10(-5) mol/l). 2. Monatepil (0.3 mg/kg i.v.) slightly decreased heart
      rate in anesthetized open-chest dogs. This drug (0.1, 0.3 mg/kg i.v.) increased
      cardiac output and decreased blood pressure and total peripheral resistance.
      Monatepil decreased left ventricular dP/dtmax and slightly increased left
      ventricular end-diastolic pressure. 3. Monatepil (0.1-1.0 mg/kg i.v.) did not
      affect the PR interval, QRS duration and QTc interval of electrocardiograms in
      anesthetized dogs, whereas diltiazem (0.3 and 1.0 mg/kg i.v.) markedly prolonged
      the PR interval. 4. Monatepil (0.1-0.3 mg/kg i.v.) increased coronary blood flow
      (CoBF) and decreased myocardial oxygen consumption (MOC) and extraction. 5.
      Monatepil and diltiazem showed almost the same effects on cardiac function and
      myocardial oxygen supply and demand, but the negative chronotropic and negative
      dromotropic effects of monatepil were less potent than those of diltiazem.

PMID- 8141819
TI  - Intravenous injection of adenosine triphosphate for assessing sinus node
      dysfunction in patients with sick sinus syndrome.
AB  - The clinical value of rapid intravenous injection of adenosine triphosphate (ATP,
      Adephos Kowa # L3, CAS 56-65-5) for assessing sinus node function was examined in
      5 patients with sick sinus syndrome (SSS) and 6 normal controls. All patients
      with SSS showed cardiac pauses longer than 3 s on a 24-h Holter ECG monitoring.
      First, after prophylactic insertion of a temporary pacemaker in the right
      ventricle, overdrive suppression test was conducted using the standard technique,
      and sinus node recovery time (SNRT) was observed to evaluate the sinus node
      function. Then, 10 min later, 10 mg of ATP was rapidly injected intravenously,
      and body surface and intracavitary ECG were continuously recorded until the basal
      state was regained. The rapid injection of ATP resulted in a slight inhibition of
      sinus node automaticity in normal subjects, but marked inhibition was in patients
      with SSS associated with suppression of AV conduction. The longest post ATP
      atrial cycle (AA interval in the intracavitary ECG showed a close inverse
      relationship with SNRT corrected for basal sinus length (CSNRT), according to the
      following formula: longest AA interval (ms) = 3.32 x CSRT (ms) +254.4 (r = 0.91,
      p < 0.001). The results suggest that rapid intravenous injection is a useful tool
      for the diagnosis of SSS.

PMID- 8141820
TI  - Sex difference in pharmacokinetics of the novel sulfonylurea antidiabetic
      glimepiride in rats.
AB  - Glimepiride (Hoe 490, CAS 93479-97-1), a novel sulfonylurea antidiabetic agent,
      was studied for the cause of sex-related difference in the elimination clearance
      of the unchanged drug in rats. After intravenous and oral administration, the
      serum level of the unchanged drug was higher in female rats and AUC and t1/2
      (beta) values were about 1.7- and 1.4-fold those for males, while Vss and oral
      bioavailability were nearly equal. The excretion clearance of the unchanged drug
      was quite small in both male and female animals, and most of the administered
      drug was excreted into the bile as a hydroxymethyl derivative, M1. In the in
      vitro metabolism study, M1 was found to be formed mainly in the liver microsomal
      fraction, and its hydroxylation activity was significantly higher in males. This
      metabolic activity was dependent on NADPH and was inhibited by proadifen. On the
      other hand, formation of M2, a carboxyl derivative, from M1 was observed in the
      cytosol fraction and showed no sex difference. Its metabolic activity depended on
      NAD and was inhibited by pyrazole. These results suggest that the sex difference
      observed in rat pharmacokinetics is mainly due to different hydroxylation
      activities of the side chain methyl group based on the participation of sex
      dependent cytochrome P-450 in liver microsomes.

PMID- 8141821
TI  - New 2-aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives as
      diuretics.
AB  - 2-Aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-4-one derivatives having various
      substituents at the 4'-position, H or methyl at 1,3-positions and nitro or amino
      at 6-position were prepared and tested for their diuretic, natriuretic and
      kaliuretic activities on male Wistar rats at a dosage of 25 mg/kg or less. 2-(3
      Pyridyl) derivatives were inactive. 1,3-Dimethyl-6-nitro-2-phenyl derivatives (1)
      were active depending on the electronic character of the 4'-substituent but at
      the same time were sodium-sparing. However, 1(H),3(H)-6-nitro-2-phenyl
      derivatives (2) were generally inactive as diuretics but active as potassium
      sparing drugs. 6-Amino-1(H),3(H)-2-phenyl derivatives (4) were active as
      diuretics depending on dipolar moment of the substituent at the 4'-position, and
      induced moderate potassium release. The 6-amino-2-(4-trifluoromethylphenyl)-1,
      2,3,4-tetrahydropyrido [2,3-d]pyrimidin-4-one (4f) remained active up to a dosage
      of 3 mg/kg. The structure-activity relationships were carried out in light of the
      adaptative least squares (ALS) method and discriminant functions for diuretic
      compounds were established.

PMID- 8141822
TI  - Effect of rebamipide on lipid peroxidation and gastric mucosal injury induced by
      indometacin in rats.
AB  - The protective effect of rebamipide (CAS 11911-87-6), a novel anti-ulcer agent,
      was investigated in rats with hemorrhagic erosions on the glandular stomach
      induced by intragastric administration of 25 mg/kg of indometacin. Pretreatment
      with 100 mg/kg of rebamipide significantly inhibited the increase in total area
      of erosions in the stomach and the increase in lipid peroxides in the gastric
      mucosa. Rebamipide also inhibited the in vitro increase of lipid peroxides in the
      gastric mucosal homogenates induced by free radical initiators. These results
      indicate that rebamipide's protective effect against indometacin-induced gastric
      mucosal injury may result, in part, from its antioxidant effect, which inhibits
      lipid peroxidation.

PMID- 8141823
TI  - Comparative pharmacokinetics of oral dextromethorphan and dextrorphan in the
      rabbit.
AB  - The pharmacokinetics of dextromethorphan (CAS 125-71-3) and its metabolite
      dextrorphan (CAS 125-73-5) was compared. The drugs were administered orally at
      the same molar dose of 0.085 mmol/kg. Plasma levels of dextromethorphan,
      dextrorphan, and metabolites 3-hydroxymorphinan and 3-methoxymorphinan were
      determined by HPLC with fluorimetric detection. Dextromethorphan was rapidly and
      extensively metabolized and the plasma profiles of dextrorphan, administered
      directly or as metabolite of dextromethorphan, were similar. The concentrations
      of 3-hydroxymorphinan were higher after dextromethorphan than dextrorphan. 3
      Methoxymorphinan was detectable only 60 and 120 min after dextromethorphan. This
      work proposes the therapeutic use of dextrorphan instead of its precursor
      dextromethorphan.

PMID- 8141824
TI  - Bronchospasmolytic activity and toxicity modelling of theophylline derivatives by
      a microcomputer based method.
AB  - The OASIS (Optimized Approach based on Structural Index Sets) microcomputer
      system was applied to model the bronchospasmolytic activity and toxicity of
      theophylline derivatives. The geometric and electronic factors responsible for
      biological activity of these compounds were determined. The molecular topology
      rather than compound metrics is the factor conditioning the theophylline
      activity. The opposite influence of topology on bronchospasmolytic activity and
      toxicity was established. Although the acceptor properties (acceptor
      superdelocalizability indices) determine both the activity and toxicity of the
      studied compounds the different positions of these effects is of decisive
      importance in both cases.

PMID- 8141825
TI  - Some new benzoxazolinone derivatives with analgesic and anti-inflammatory
      activities.
AB  - Fourteen new 6-acyl-2-benzoxazolinone, ethyl-(6-acyl-2-benzoxazolinone) acetate
      and (6-acyl-2-benzoxazolinone-3-yl) acetic acid derivatives were synthesized, and
      their physical properties and UV absorption data were determined. Their chemical
      structures were elucidated by IR, 1H-NMR and elemental analysis. The analgesic
      activities of these compounds were investigated by a modified Koster's test. It
      was shown that the respective activities of compounds 1-4 and 10-14 were higher
      than that of acetylsalicylic acid. Therefore, they were screened for additionally
      anti-inflammatory activities using the carrageenan mouse paw edema test. The
      compounds were further screened for their ability to inhibit prostaglandin E2
      (PGE2) induced paw edema and compared to indometacin. Compounds 12 and 13 were
      very potent in inhibiting PGE2 induced edema.

PMID- 8141826
TI  - Preparation of new Schiff bases derived from beta-enaminonitriles and
      hetarylcarboxaldehydes. Anti-inflammatory and ulcerogenic activities.
AB  - Schiff bases 3a-j were prepared by reacting the beta-enaminonitriles (1a,b) with
      the appropriate hetarylcarboxaldehyde, in boiling ethanol. Structural
      elucidations for the new compounds (3a-j) were based upon compatible analytical
      and spectroscopic results. Compounds 1a, 1b, 3a, 3c, 3d and 3i were tested for
      their anti-inflammatory and ulcerogenic activities.

PMID- 8141827
TI  - Steady state disposition of 5-aminosalicyclic acid following oral dosing.
AB  - In 18 healthy volunteers the steady state disposition of 5-aminosalicylic acid (5
      ASA, mesalazine, CAS 89-57-6; 500 mg tid) was evaluated following the last oral
      dose in form of slow release tablets (Salofalk) either containing 500 mg or 250
      mg 5-ASA. In none of the pharmacokinetic parameters of 5-ASA characterizing
      bioavailability (e.g. AUC approximately 6 ug/ml x h; Cmax approximately 1.7
      micrograms/ml; tmax approximately 5 h; Cminss approximately 0.5 micrograms/ml;
      Cavss approximately 0.75 microgram/ml) differences between both forms were
      observed and the calculated 90% confidence intervals and point estimates
      indicated bioequivalence. Following the delayed absorption 5-ASA was rapidly
      eliminated (t1/2 = 1.4 +/- 0.5 h).

PMID- 8141828
TI  - Studies on lipoate effects on blood redox state in human immunodeficiency virus
      infected patients.
AB  - Several investigators have implicated that human immunodeficiency virus (HIV)
      infected patients have a compromised antioxidant defense system. Blood
      antioxidants are decreased and peroxidation products of lipids and proteins are
      increased in the patients. This may have pathophysiological implications, because
      antioxidants, such as glutathione, and reactive oxidants are involved in the
      regulation of the human immunodeficiency virus. Consequently it was suggested
      that HIV infected patients may benefit from antioxidant supplementation therapy.
      In a open and unblinded pilot study the short term effect of the natural
      antioxidant lipoate (Thioctacid) on blood antioxidants and peroxidation products
      was investigated in HIV positive patients (CDC IV). In the majority of the
      patients, lipoate increased plasma ascorbate (9 of 10 patients) total glutathione
      (7 of 7 patients), total plasma thiol groups (8 of 9 patients); T helper
      lymphocytes and T helper/suppressor cell ratio (6 of 10 patients), while the
      lipid peroxidation products malondialdehyde (8 of 9 patients) and 4
      hydroxynonenal (7 of 9 patients) were decreased. The results of this pilot study
      indicate that lipoate supplementation changes the blood redox state of HIV
      infected patients. A prospective and longitudinal therapy study is warranted to
      investigate the long term effects of lipoate therapy on blood redox state,
      disease progression and incidence of opportunistic infections in HIV infected
      patients.

PMID- 8141829
TI  - Synthesis and antiviral activity of some new benzofuran derivatives.
AB  - New derivatives of benzofuran were prepared and evaluated for their in vitro
      activity against a number of DNA and RNA viruses in various cell systems.
      Compounds 1-(7-dodecyloxy-2-benzofuranyl)ethanone (3c) and 1-(7-tridecyloxy-2
      benzofuranyl)ethanone (3d) exhibited a specific activity against respiratory
      syncytial virus in HeLa and compound [di(2-acetylbenzofuranyl-7-oxy)]-n-propane
      (5a) against influenza A virus in MDCK.

PMID- 8141830
TI  - Disposition of the novel anticancer agent vinorelbine ditartrate following
      intravenous administration in mice, rats and dogs.
AB  - 1. KW-2307 (vinorelbine ditartrate, CAS71486-22-1) is a new semisynthetic
      antitumour vinca alkaloid. Its pharmacokinetics, distribution and excretion were
      investigated following intravenous administration to mice (1.2 mg/kg), rats (0.12
      and 1.2 mg/kg) and dogs (0.4 mg/kg). Dose levels are expressed as the free base.
      2. Plasma concentrations of drug-related radioactivity declined in a bi- or tri
      exponential manner, initially rapidly and then slowly (half-life of 35 h or
      more). Unchanged drug concentrations declined with terminal half-lives of 35.8 h
      in rats and 34.5h in dogs: a terminal phase was not observed in mice. KW-2307 can
      be characterised as a drug of high clearance (3.78, 1.73 and 1.20 l/h/kg in the
      mice, rats and dogs, respectively) and large volume of distribution (12.7, 41.9
      and 49.6 l/kg in the mouse, rat and dog, respectively). After repeated
      administrations for 21 days in the rat, the accumulation ratio for unchanged drug
      concentrations in plasma was 1.5. 3. The extent of binding of 3H-KW-2307 in vitro
      to proteins in the plasma of humans, dogs, rats and mice was 89, 90, 93 and 97%,
      respectively. 4. In rats, concentrations of radioactivity in most tissues
      exceeded those in plasma, and at 0.5 h after administration were greatest in the
      adrenals, thyroid, pituitary, lungs, small intestine contents and kidneys. The
      lung is a target for drug action. Concentrations of radioactivity in the brain
      were lowest. In pregnant rats, placental transfer of radioactivity was low, less
      than 1% of the dose. Concentrations in mammary tissue, another target for drug
      action, exceeded those in plasma. The tissue distribution profile of
      radioactivity in rats was similar after single and repeated administrations. 5.
      Radioactivity was excreted mainly in faeces (61-73% dose in 48 h and 71-79% dose
      in 168 h). Biliary excretion accounted for 42.6% dose in rats during 48 h
      although enterohepatic cycling was probably unimportant.

PMID- 8141831
TI  - [Evaluation of the serum bactericidal test].
AB  - The serum bactericidal test (SBT) is used to monitor antibiotic treatment during
      therapy. Compared to other methods of sensitivity testing, such as MIC (minimum
      inhibitory concentration) determination, the SBT also takes into consideration
      the pharmacokinetic qualities of the drug tested. Serum bactericidal titers are
      measured during therapy of different infectious diseases to estimate therapeutic
      outcome. Until now serum bactericidal titers of 1:8 in non-granulocytopenic
      patients, and titers > or = 1:16 in granulocytopenic patients have been shown to
      correlate with a successful treatment outcome in patients with gram-negative
      sepsis. In patients with endocarditis a peak serum bactericidal titer of at least
      1:32 should be achieved. Another way to apply the serum bactericidal test is to
      compare the activity of different antibiotics in volunteers. The present study as
      well as data from the literature indicate that ciprofloxacin has markedly higher
      serum bactericidal activity than ofloxacin. Of the so called "basic
      cephalosporins" cefotiam achieved the highest serum bactericidal activity against
      the Enterobacteriaceae tested. Since 3rd generation cephalosporins are in general
      highly active against gram-negative rods, we were interested in using the SBT to
      compare different dosage regimens. In several studies serum bactericidal titers
      of > or = 1:8 were achieved with the 1 g dosis of cefotaxime, cefmenoxime and
      especially ceftazidime against the gram-negative rods tested.

PMID- 8141832
TI  - Mammalian cell cultures. Part III: Safety and future aspects.
AB  - Long standing experience with mammalian cell cultures demonstrates that they per
      se do not constitute any hazard to healthy man. However, permanent cell lines may
      cause transplantable tumors in immune-suppressed animals and man but not in
      healthy species. A potential hazard associated with mammalian cell cultures might
      be caused by endogenous viruses which can be harboured in the mammalian cells or
      adventitious agents associated with mammalian cells. Especially a corresponding
      validation for removal of viruses has to be established in the manufacturing
      process. Free nucleic acids or recombinant nucleic acid sequences are regarded as
      not being biologically active and therefore do not cause any hazard. Because
      mammalian cell cultures which are ranking lowest in terms of safety measures are
      able to synthesize reliably complex glycoprotein structures, the economy of
      mammalian cell culture processes has to be approved for future prospects on the
      background of the competitive situation with microorganisms and the overall cost
      limitation of the health insurance systems. High yielding expressing systems are
      required including detoxification genes for cytotoxic metabolites. Shorter
      doubling times of the host cell, higher productivity and higher cell densities
      would be further goals. Also new aspects of mammalian cell cultures, not only
      their use as factories for protein synthesis, but also in gene therapy as carrier
      for the desired genetic information or in enhancing the wound healing process,
      will gain future importance.

PMID- 8141833
TI  - Familial defective apolipoprotein B-100: a review, including some comparisons
      with familial hypercholesterolaemia.
AB  - Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder
      caused by the substitution of glutamine for arginine at position 3500 in apo B
      100. The presence of mutant apo B-100 in low-density lipoproteins (LDL) markedly
      reduces their affinity for the LDL receptor, leading to hypercholesterolaemia and
      increased proneness to coronary artery disease. In some FDB heterozygotes the
      clinical picture is indistinguishable from that in heterozygous familial
      hypercholesterolaemia (FH). In European and N. American populations the frequency
      of FDB is at least as high as that of FH. In most lipid clinics, 2-5% of patients
      given a clinical diagnosis of FH have FDB, not FH. Most FDB heterozygotes respond
      well to drugs that lower plasma LDL levels by inducing receptor activity. This
      may be due partly to increased receptor-mediated hepatic removal of mutant and
      normal precursors of LDL, using apo E as recognition element. Several important
      lessons can be learnt from the study of FDB.

PMID- 8141834
TI  - Identification of a functional receptor differing from the LDL receptor that
      catabolizes chylomicron remnant in Hep G2 cells.
AB  - We investigated types of lipoprotein receptors on Hep G2 cells using a monoclonal
      antibody against the LDL receptor. IgG-C7 inhibited the binding and
      internalization of 125I-labeled low density lipoprotein (LDL) in Hep G2 cells
      with upregulated and downregulated LDL receptors by 90% of control values.
      Binding and internalization of 125I-labeled chylomicron remnant in Hep G2 cells
      with upregulated and downregulated LDL receptors was 50% and 85%, respectively,
      of control values after exposure to IgG-C7. Excess unlabeled chylomicron remnant
      inhibited binding and internalization of 125I-labeled chylomicron remnant in Hep
      G2 cells with downregulated LDL receptors completely. Pronase treatment abolished
      binding and internalization of 125I-labeled LDL and 125I-labeled chylomicron
      remnant in Hep G2 cells. When solubilized fractions of Hep G2 cells were
      immunoprecipitated with IgG-C7, the binding activity of 125I-labeled chylomicron
      remnant to reconstituted vesicles was unchanged. 45Ca blotting analysis showed
      the presence of 45Ca binding protein (approximately 600 kDa) in Hep G2 cells. The
      amount of 45Ca binding protein was not affected by cholesterol and was abolished
      by pronase treatment. These results suggest the existence of a functional
      receptor other than the LDL receptor that catabolizes chylomicron remnant in Hep
      G2 cells and that this receptor may correspond to LDL receptor-related protein.

PMID- 8141835
TI  - An acceptor splice site mutation in intron 16 of the low density lipoprotein
      receptor gene leads to an elongated, internalization defective receptor.
AB  - In this report, we describe the characterization of a mutation in the low density
      lipoprotein (LDL) receptor gene of a true homozygous familial
      hypercholesterolemic (FH) patient. The combined use of denaturing gradient gel
      electrophoresis (DGGE) and DNA sequence analysis revealed a unique A to G
      transition in the penultimate 3'-nucleotide of intron 16 of the LDL receptor
      gene, which disrupts the acceptor splice site. cDNA sequence analysis indicated
      that a cryptic splice site was activated in intron 16, upstream from the original
      splice site, leading to the inclusion of 62 nucleotides and a reading frame
      shift. The resulting new translation product contains a stretch of 154 amino
      acids at the carboxy-terminal that have no resemblance to the normal receptor
      protein. To elucidate the biological effects of the mutation, the structural and
      functional properties of the mutated LDL receptor protein were studied.
      Immunoprecipitation of the newly synthesized LDL receptors showed that an
      aberrant precursor form of the LDL receptor protein was synthesized, about 10 kDa
      larger than normal, which is not further processed to the mature form. Some 50%
      of the normal LDL binding activity was found on the cell surface of the patient's
      fibroblasts, whereas internalization and degradation of LDL were abolished.

PMID- 8141836
TI  - Protection of low-density lipoprotein against oxidative modification by high
      density lipoprotein associated paraoxonase.
AB  - We have investigated the Cu2+ induced generation of lipid peroxides in low
      density lipoprotein (LDL) incubated with high density lipoprotein (HDL) and with
      purified paraoxonase, an enzyme normally resident on HDL. HDL (1.5 mg) and
      paraoxonase (20 micrograms) inhibited lipid peroxide generation in LDL by 32% and
      25%, respectively after 24 h of incubation (both P < 0.01). The decrease in LDL
      lipid peroxides both with HDL and with paraoxonase were concentration dependent.
      The degree of protection offered by HDL tended to relate to its paraoxonase
      activity (R = 0.47; P < 0.06). Neither purified paraoxonase nor HDL chelated Cu2+
      sufficiently to account for the decrease in LDL oxidation. Purified paraoxonase
      did not affect LDL oxidation when it had been heat inactivated. Mass transfer of
      lipid peroxides from LDL to HDL did not explain the protection of LDL against
      oxidation: the total lipid peroxides accumulating during incubation was decreased
      both by HDL and by paraoxonase. These results suggest a direct role for HDL in
      preventing atherosclerosis probably by an enzymic process which prevents the
      accumulation of lipid peroxides on LDL. Paraoxonase is an example of an enzyme
      which might possibly be involved.

PMID- 8141837
TI  - Protein kinase C pathway and proliferative responses of aged and young rat
      vascular smooth muscle cells.
AB  - Alterations of vascular smooth muscle cell (VSMC) proliferation have been
      implicated in the age-dependent susceptibility to atherosclerosis. Although it is
      known that protein kinase C (PKC) is involved in the mechanism of VSMC
      proliferation, there are no data on the possible involvement of PKC in
      disregulating VSMC proliferation in aged vascular cells. We evaluated the
      proliferative pattern, the PKC responsiveness and the effect of phorbol ester
      (PMA) treatment on vascular cell growth and cell cycle distribution in VSMCs from
      young and aged rats. The proliferative response was significantly higher in aged
      than in young cells after serum stimulation (7.5 vs. 2.8 x 10(4), 18 vs. 12 x
      10(4), 26 vs. 22 x 10(4) cells/well, aged vs. young at days 2, 4, 6; P < 0.005).
      On the contrary, aged cells showed a significant inhibition of DNA synthesis at
      48 h incubation with PMA concentrations of 1, 10, 100 nM (-47%, -53%, -58%,
      respectively) compared with controls (fetal calf serum 0.5%) and cell count
      (average decrease: -38% from 48 h to 96 h) after treatment with PMA 10 nM. The
      opposite was observed in young cells on [3H]thymidine incorporation with PMA 1,
      10, 100 nM (+52%, +100%, +121%, respectively and cell count (average increase
      +55% from 48 h to 96 h). In addition, inhibition of the cell cycle from G1 to the
      S phase and reduction of PKC translocation in aged VSMC were observed.
      Alterations of PKC function could be involved in the disregulation of aged VSMC
      proliferation, which seems to characterize the increased susceptibility to
      atherosclerosis.

PMID- 8141838
TI  - Effect of lovastatin on the secretion of very low density lipoprotein lipids and
      apolipoprotein B in the hypertriglyceridemic Zucker obese rat.
AB  - Recent studies demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase lower plasma triglyceride primarily by decreasing
      hepatic secretion of very low density lipoproteins (VLDL). A possible mechanism
      is that inhibition of cholesterol synthesis interferes with the assembly of VLDL
      particles. Since one molecule of apolipoprotein (apo) B is required for the
      proper assembly and secretion of each VLDL and secretion of apo B may be
      regulated by various lipid components of the lipoproteins, question arises
      whether HMG-CoA reductase inhibitors also decrease the secretion of apo B. To
      address this issue, we investigated the effect of lovastatin on the secretion
      rate of VLDL-apo B and on the composition of VLDL in the Zucker obese rat; a
      model for genetic hypertriglyceridemia. Lovastatin treatment (4 mg/kg day x 13
      days), as compared with placebo, decreased the concentrations of fasting plasma
      triglyceride (1740 +/- 170 vs. 3130 +/- 790 micrograms/ml) and VLDL-triglyceride
      (1379 +/- 59 vs. 3082 +/- 715 micrograms/ml). There was a small but non
      significant decrease in VLDL-apo B (19 +/- 2 micrograms/ml vs. 26 +/- 7
      micrograms/ml). Thus, lovastatin significantly decreased the ratio of
      triglyceride to apo B in VLDL (76 in lovastatin vs. 124 in placebo group).
      Secretion rates of VLDL-lipids and VLDL-apo B were measured after intravenous
      injection of Triton WR-1339.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141839
TI  - Phenotypic expression of familial hypercholesterolaemia in central and southern
      Tunisia.
AB  - We studied 14 families with familial hypercholesterolaemia (FH) from Central and
      Southern Tunisia. Twenty-six living homozygotes were identified in these areas of
      whom 24 homozygotes and 27 of their obligate heterozygote parents are the subject
      of this report. Ten of the 14 families are unrelated and in 9 of them there were
      consanguineous marriages. The mean age of homozygotes was 16 for females (range
      2.5-40) and 12.5 for males (range 2-34). All the homozygotes had extensive
      xanthomatosis and showed variable clinical manifestations of coronary heart
      disease (CHD). Plasma total and LDL cholesterol levels averaged 18 and 16.9
      mmol/l, respectively. Mean high density lipoprotein (HDL) cholesterol values were
      0.48 mmol/l for males and 0.70 mmol/l for females. The mean age of the obligate
      heterozygotes was 44 (range 32-62 years) for mothers and 51 (range 35-80 years)
      for fathers. None of them had tendon xanthomas, not even the oldest, who was aged
      80. Only 5 of the 27 obligate heterozygotes had developed CHD (aged 34-58).
      Plasma cholesterol levels varied more than twofold (4.1-10 mmol/l) and averaged
      6.79 and 7.51 mmol/l for males and females, respectively. LDL cholesterol values
      were below the age- and sex-related 95th percentile from the Lipid Research
      Clinics Prevalence Study in 46% of male and 30% of female heterozygotes. The
      frequency of homozygotes was 1:125,000 and the minimum estimated frequency of
      heterozygotes was 1:165 in Central and Southern Tunisia. Only Afrikaners in South
      Africa and French Canadians have such high frequencies of FH.

PMID- 8141840
TI  - Variability in cholesterol content and physical properties of lipoproteins
      containing apolipoprotein B-100.
AB  - The primary objective of this study was to determine the variability in
      cholesterol carrying capacity of low density lipoproteins (LDLs) and other
      apolipoprotein B (apo B)-containing lipoproteins in normolipidemic men. One
      hundred and fifty-nine normolipidemic men, ages 21 to 73 years, were enrolled. In
      addition to determining plasma lipids and lipoproteins, three primary
      measurements were made: ratios of cholesterol to apo B in LDL; the
      electrophoretic pattern of LDL, i.e. pattern A, AB, or B; and levels of
      cholesterol in all lipoproteins other than high density lipoproteins (nonHDL
      cholesterol) along with total apo B. First, the data revealed that about 85% of
      the variability of LDL-cholesterol levels can be accounted for by LDL-apo B
      levels, whereas the remaining 15% can be explained by differences in LDL
      cholesterol/apo B ratios. Second, LDL electrophoretic pattern A was the
      predominant pattern in young adult men, but in older men the pattern shifted
      increasingly to AB and B. And third, there was a high correlation between nonHDL
      cholesterol levels and total apo B levels, which suggests that nonHDL-cholesterol
      can be used as a relatively accurate surrogate for total apo B levels in
      normolipidemic individuals.

PMID- 8141841
TI  - Serum apolipoprotein(a) correlates with growth hormone levels in Chinese patients
      with acromegaly.
AB  - Untreated acromegaly is associated with an increased cardiovascular morbidity and
      mortality. The contribution of altered lipid metabolism remains unclear. We
      investigated the relationship between serum apolipoprotein(a) (apo(a)) and growth
      hormone (GH) levels in 15 patients with acromegaly before and during treatment
      with octreotide, a long-acting somatostatin analogue, 288-600 micrograms/day
      s.c., for 6 months. Before treatment serum apo(a) was significantly elevated in
      acromegalic patients (geometric mean being 323 U/l vs. 142 U/l in controls (n =
      92; P < 0.01)). Octreotide treatment resulted in significant reductions in serum
      apo(a) concentration (F = 7.22; P < 0.01; geometric mean being 232 U/l and 248
      U/l at 3 months and 6 months respectively) and apo(a) concentrations on treatment
      were not significantly different from control values. There were significant
      reductions in serum GH (F = 7.30; P < 0.01), insulin growth factor 1 (IGF1) (F =
      31.4, P < 0.001) and insulin (F = 4.57; P < 0.05) concentrations. Plasma
      glycosylated haemoglobin levels were unchanged. Apo(a) levels correlated with
      serum GH (r = 0.450; P < 0.01) but showed no correlation with basal insulin
      concentrations. Serum HDL cholesterol increased on treatment (F = 4.29; P <
      0.05). Triglycerides were reduced only in the 12 patients without diabetes
      mellitus (F = 4.75; P < 0.05). No significant change in LDL cholesterol occurred.
      Our findings suggest that apo(a) may constitute another cardiovascular risk
      factor in untreated acromegaly and that GH may be involved in the regulation of
      circulating apo(a) concentration.

PMID- 8141842
TI  - Arterial permeability dynamics and vascular disease.
AB  - There is a growing consensus that regional susceptibility to atherosclerosis
      correlates topographically with an increased endothelial permeability to
      macromolecules such as low-density lipoprotein. Earlier research suggested that
      increases in arterial macromolecular permeability accompany the adaptation of the
      endothelial lining to changes in fluid dynamic shear stress, and that
      permeability might therefore be chronically increased where the endothelium is
      exposed to a shear stress environment that changes throughout the day. Thus the
      temporal variability of hemodynamic stresses at the vessel wall, with time
      constants of many minutes or a few hours, may affect local susceptibility to
      disease. Changes in the hemodynamic stresses on the endothelial surface ('local'
      stress) result from the normal variations in more 'global' hemodynamic variables
      such as blood flow rate, heart rate, and flow partition at branches, that occur
      throughout the day in response to changes in peripheral metabolic demand. Thus,
      at any given time, the permeability at a site is determined by: (1) the steady
      state relationship between the local permeability and local shear stress; (2) the
      dynamics of the permeability change induced by changes in local shear; and (3)
      the extent to which the shear stress at the site is affected by changes in the
      global variables. Regional variations in any or all of these three factors can
      lead to corresponding variations in endothelial permeability, macromolecular
      uptake and, apparently, atherosclerotic risk. Among the three factors, the first
      may be relatively unimportant if most transport takes place while the endothelium
      is responding to hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141843
TI  - Requirement for mevalonate in acetylated LDL induction of cholesterol
      esterification in macrophages.
AB  - HMG-CoA reductase inhibitors simvastatin, fluvastatin and fluvastatin enantiomers
      (0.1 to 5 microM) were utilized to block both mevalonate formation and
      cholesterol esterification in mouse peritoneal macrophages in the presence of a
      large excess of cholesterol supplied by acetylated LDL. Supplementation of
      cultures with mevalonate fully reversed, in a dose-dependent manner, the
      inhibitory effect of the drugs on cholesterol esterification. Mevalonate alone,
      in the range of the tested concentrations, did not affect cholesterol
      esterification in the absence of the HMG-CoA reductase inhibitors, indicating
      that its effect was linked to the restoration of the endogenous pool depleted by
      the pharmacological block of HMG-CoA reductase. The inhibitory effect of
      fluvastatin was also prevented by the non-sterol mevalonate isoprenoid derivative
      geranylgeraniol. Evaluation of fluvastatin enantiomers demonstrated the
      stereospecificity of drug action with most of the effect associated to the
      antipode with the highest inhibitory activity of HMG-CoA reductase. We conclude
      that mevalonate or a mevalonate product(s), possibly a non-sterol derivative(s),
      are required in cholesterol esterification induced by acetylated LDL in
      macrophages.

PMID- 8141844
TI  - Familial lecithin:cholesterol acyltransferase deficiency: further resolution of
      lipoprotein particle heterogeneity in the low density interval.
AB  - Patients presenting with a familial deficiency of lecithin:cholesterol
      acyltransferase (LCAT) typically exhibit multiple quantitative and qualitative
      perturbations of apo B- and apo A-I-containing plasma lipoproteins. Marked
      particle heterogeneity has been detected over the low-density range (d = 1.019
      1.063 g/ml), involving lipoprotein(X) (LP-X) and large molecular weight LDL (LM
      LDL). We describe the chromatographic fractionation and characterization of the
      major particle species distributed within the low-density interval in a new
      French LCAT-deficient family. Detailed analyses of the plasma lipoprotein and
      apolipoprotein spectrum are reported. The plasma lipoproteins were enriched in
      unesterified cholesterol and phospholipids with markedly reduced concentrations
      of cholesteryl esters. By a combination of gel filtration and affinity
      chromatography on heparin-sepharose, the heterogeneous mixture of low-density
      particles was resolved into three distinct particle populations: LP-X (diameter
      400 A) corresponding to LM-LDL, an apo A-I and albumin-containing particle
      similar to LP-X2 (diameter 300 A), and cholesteryl ester-deficient (0.9%)
      triglyceride-rich (58.4%) LDL containing apo B-100 (diameter 260-270 A). Use of
      affinity chromatography allowed separation of HDL-like particles (diameter 140
      160 A) which were rich in free cholesterol (21.4%) and phospholipids (52.9%) and
      which were isolated in association with LP-X upon gel filtration chromatography.
      Ultracentrifugal density gradient analysis of plasma from the LCAT-deficient
      subject over a period of 3 years showed a net shift of the lipoprotein
      distribution in the low density range due to an increase in plasma LP-X levels.
      We propose that the presence of LP-X in the plasma is correlated with a
      progressive alteration in the renal function recently observed in this patient.

PMID- 8141845
TI  - Copper- and malondialdehyde-induced modification of high density lipoprotein and
      parallel loss of lecithin cholesterol acyltransferase activation.
AB  - Incubation of high density lipoproteins (HDL) with 0.1-10 microM copper ions
      resulted in a decrease in tryptophan residues and a moderate diminution of lysine
      residues. Polymerization of apolipoprotein AI (apo A-I) was only observed for the
      highest concentration of Cu2+. A dose-dependent loss in lecithin cholesterol acyl
      transferase (LCAT) activity was noted. Following incubation with 10 mM
      malondialdehyde, the physicochemical properties of HDL were more pronouncedly
      affected, in terms of lipid peroxidation products, relative electrophoretic
      mobility and percentages of intact tryptophan and lysine residues. Polymerization
      of apo A-I occurred after 40 min incubation, and a time-dependent loss of LCAT
      activation was noted. Since the deficiency in LCAT activation was observed in
      relatively mild conditions, when no perturbation of the physico-chemical
      properties of the particle could be shown, the determination of LCAT activity
      appears to be a sensitive test for HDL discrete modification.

PMID- 8141846
TI  - A possible protective role of veins against atherosclerosis.

PMID- 8141847
TI  - Plasma lipoprotein(a) concentrations are not elevated by cardiopulmonary bypass.

PMID- 8141848
TI  - Platelet inhibitory functions of aortic endothelial cells. Effects of
      eicosapentaenoic and docosahexaenoic acids.
AB  - The endothelial cell platelet inhibitory potential was assessed directly by
      measuring the platelet inhibition induced by platelet interaction with the
      cultured aortic endothelial cell. The prostacyclin content of the platelet
      suspensions after interaction was also quantified. We found that prostacyclin
      production accounted for the overall platelet inhibitory potential of the aortic
      cells since: (a) endothelial cells incubated with aspirin, which did not produce
      prostacyclin, did not inhibit platelets; (b) the prostacyclin content of platelet
      suspensions after interaction with endothelial cells correlated with the extent
      of the platelet inhibition; (c) such a platelet inhibition was reproduced by
      adding synthetic prostacyclin in amount equivalent to that produced by
      endothelial cells during the interaction. Eicosapentaenoic (EPA) and
      docosahexaenoic (DHA) acids incorporated into endothelial phospholipids,
      decreased the ability of the cells to produce prostacyclin and to inhibit
      platelets, DHA being less effective than EPA.

PMID- 8141849
TI  - The relation of atherosclerotic lesions to antemortem and postmortem lipid
      levels: the Bogalusa Heart Study.
AB  - Although postmortem lipid levels have been used as surrogates for levels during
      life, it is uncertain whether atherosclerotic lesions are related similarly to
      antemortem and postmortem lipid values. In a sample of 23 children and young
      adults who had been examined for cardiovascular disease risk factors and
      subsequently died from violent causes, we examined the relation of (a) postmortem
      lipid levels to values obtained 1 to 14 years earlier, and (b) atherosclerotic
      lesions to antemortem and postmortem lipid levels. Postmortem levels of
      triglycerides and very-low-density lipoprotein cholesterol (VLDLC) were higher
      than levels during life, but postmortem levels of total cholesterol (TC), low
      density lipoprotein cholesterol (LDLC) and high-density lipoprotein cholesterol
      (HDLC) were related to antemortem levels (rs > 0.40). After excluding eight
      persons who likely received large volumes of intravenous fluids before death, the
      within-person variability between antemortem and postmortem levels of LDLC and
      HDLC was similar to the antemortem variability. Furthermore, the relation of
      atherosclerotic lesions to antemortem and postmortem lipid levels differed only
      slightly for TC, LDLC and HDLC. In contrast, lesions in the coronary arteries
      showed the strongest association with antemortem VLDLC levels, but were not
      associated with postmortem VLDLC levels. Despite the very small number of
      subjects, our results suggest that if intravenous fluids are not administered
      before death, postmortem levels of TC, LDLC and HDLC are fairly representative of
      levels during life. Postmortem levels of VLDLC or triglycerides, however, should
      not be used as surrogates for antemortem levels.

PMID- 8141850
TI  - Prevalence of coronary heart disease and associated risk factors among elderly
      Finnish men in the Seven Countries Study.
AB  - The prevalence of coronary heart disease (CHD), cardiovascular disease (CVD) and
      associated risk factors was studied in 413 men aged 70-89, the survivors of the
      Finnish cohorts of the Seven Countries Study. Men were divided into five
      categories according to manifestations of prevalent CVD: I, history or ECG
      evidence of previous myocardial infarction (MI; 48 men, 12%); II, typical angina
      pectoris (AP; 56 men, 14%); III, other ischaemic electrocardiographic (ECG)
      changes (82 men, 20%); IV, stroke, transient ischaemic attack, intermittent
      claudication or minor ECG changes (other CVD; 78 men, 19%); V, free of CVD (149
      men, 36%). Both systolic and diastolic blood pressures were lowest in men with
      previous MI and in men free of CVD, and highest in men with other ischaemic ECG
      changes (P = 0.017). Low HDL-cholesterol (< 0.9 mmol/l) was more prevalent and
      the total/HDL-cholesterol ratio and triglyceride levels were higher in men with
      prevalent CHD (P < 0.05). Total and LDL-cholesterol, smoking, body mass index,
      fibrinogen, coagulation factor VIIc, apolipoprotein A-I, apolipoprotein B and
      lipoprotein(a) were not associated with prevalent CVD. The results show that
      manifestations of CHD and CVD are common among elderly Finnish men. Low HDL
      cholesterol, total/HDL ratio, triglycerides and hypertension were associated with
      manifest CVD cross-sectionally.

PMID- 8141851
TI  - Accelerated cholesteryl ester transfer in noninsulin-dependent diabetes mellitus.
AB  - Alterations in core lipid composition of lipoproteins in noninsulin-dependent
      diabetes mellitus (NIDDM) patients have suggested that the heteroexchange of
      neutral lipids between HDL and the apo B-containing lipoproteins may be enhanced.
      For this reason, we studied cholesteryl ester transfer (CET) in ten sulfonylurea
      treated patients with stable NIDDM. CET measured in all NIDDM subjects with an
      assay of mass transfer was significantly greater than that of controls at 1 and 2
      h (P < 0.001); the transfer of radiolabeled CE also was increased in a subset of
      four of the NIDDM group (NIDDM k = 0.21 +/- 0.04 vs. control k = 0.10 +/- 0.05; P
      < 0.05). A weak correlation was demonstrable between the mass of CE transferred
      at 1 h and diabetic control expressed as plasma fructosamine (r = 0.58, P <
      0.09). To characterize this disturbance in CET further, the donor (HDL + VHDL)
      and acceptor (VLDL + LDL) lipoprotein fractions were isolated by
      ultracentrifugation at d 1.063 g/ml from NIDDM and control plasma and a series of
      recombination experiments were performed. Combining NIDDM acceptor with control
      donor fractions that contained HDL and CETP and not the combination of NIDDM
      donor and control acceptor lipoproteins resulted in an accelerated CET response
      identical to that observed in NIDDM whole plasma. This observation indicated that
      the abnormality in CET in NIDDM was associated with the VLDL + LDL
      fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141852
TI  - Inhibition of smooth muscle cell proliferation and DNA synthesis by Vasoprin--a
      biologic response modifier.
AB  - The effect of Vasoprin, a biologic response modifier (BRM), on smooth muscle cell
      DNA synthesis and intimal proliferation was studied. In this report, we have
      measured DNA specific activity (SA) and intimal thickening following balloon
      injury (balloon de-endothelialization (BDE)) after administration of Vasoprin.
      Various dose schedules were employed to assess Vasoprin's effect post BDE. Forty
      eight hours following vascular injury (the peak of SMC DNA synthesis), Vasoprin
      administered at various treatment schedules showed between 54% and 72.6% +/- 9%
      (P < 0.0012) inhibition of DNA SA compared with vehicle controls. Vasoprin also
      diminished SMC intimal thickening following its administration. Seven days after
      vascular injury, at which time SMC neointimal proliferation reaches its peak,
      Vasoprin treated animals showed marked reduction in intimal thickening by 45.5%
      +/- 6.6% (P < 0.008), compared with the BDE rats receiving an agent vehicle as
      controls. The results of this report demonstrate that a biologic response
      modifier (Vasoprin) has a profound effect on SMC proliferation, and that the
      immune system may be a component in the progression of intimal thickening and
      hence vascular closure.

PMID- 8141853
TI  - Apolipoprotein(a) genetic polymorphism and serum lipoprotein(a) concentration in
      patients with peripheral vascular disease.
AB  - Serum lipoprotein(a) (Lp(a)) levels were measured in 89 men with peripheral
      vascular disease (PVD) and 129 (100 male and 29 woman) healthy controls.
      Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in all
      subjects. Patients with PVD had significantly higher serum Lp(a) levels than
      controls. Apolipoprotein(a) phenotype frequencies in patients with PVD did not
      differ from those of the control group. Both patients and controls with phenotype
      S2 had higher serum Lp(a) levels than those with phenotype S4. It should be
      emphasized that serum Lp(a) levels were significantly higher in PVD patients than
      controls for those with phenotype S2, S3/S4 and S4. Raised serum Lp(a) levels
      together with other lipoprotein abnormalities in patients with PVD imply a high
      cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) levels
      both in patients and controls. In patients with PVD, environmental and/or other
      genetic factors must play a role in raising Lp(a) levels.

PMID- 8141854
TI  - Eicosapentaenoic acid and docosahexaenoic acid suppress the proliferation of
      vascular smooth muscle cells.
AB  - Eicosapentaenoic acid, which is one of the n-3 polyunsaturated fatty acids
      (PUFA), is reported to exert its antithrombotic and anti-atherogenic effect
      partly through the modulation of vascular cell functions. Vascular smooth muscle
      cell (VSMC) proliferation plays an important role in the pathogenesis of
      atherosclerosis. We reported the differential effect of various PUFA on VSMC
      proliferation. First we established a method for preparing PUFA rich cells in
      culture to mimic the in vivo situation using PUFA triacylglycerol emulsion. Using
      these fatty acid rich cells, we found that only EPA and docosahexaenoic acid,
      although less potent than EPA, inhibited the proliferation of VSMC among the
      fatty acids tested. This effect of EPA was reversed by the addition of anti
      oxidants. It is suggested that production of the oxidized species at a low
      concentration from EPA inhibited the proliferation of VSMC. This anti
      proliferative effect of EPA and DHA on VSMC could partly explain the anti
      atherosclerotic effect of marine lipids.

PMID- 8141855
TI  - Control of cytomegalovirus retinitis using sustained release of intraocular
      ganciclovir.
AB  - An experimental intravitreal sustained-release device containing ganciclovir was
      used to treat 22 patients with acquired immunodeficiency syndrome-associated
      cytomegalovirus retinitis. Fourteen eyes were excluded (five not involved and
      nine with macular scarring and/or severe debility). Thirty eyes received the
      ganciclovir intraocular device implant and were prospectively followed up from 16
      to 419 days (median, 125 days). Twenty-seven (90%) of 30 eyes showed
      stabilization of the retinitis. Nine (33%) of 27 eyes showed reactivation of the
      retinitis once the device was empty of ganciclovir; seven received a replacement
      device, with subsequent stabilization of the retinitis. Postoperative
      complications included vitreous hemorrhage (n = 1), endophthalmitis (n = 1), and
      progressive retinitis (n = 2). Late retinal detachment was seen in three eyes
      (11%) at 35 to 140 days. Survival analysis of all 30 eyes revealed the mean time
      to progression of retinitis to be 19 weeks (133 days). The ganciclovir
      intraocular device offers a promising alternative for the treatment of
      cytomegalovirus retinitis associated with acquired immunodeficiency syndrome.

PMID- 8141856
TI  - The relationship of academic measures in medical school to performance after
      graduation.
AB  - This study examined the relationship between academic variables in medical school
      and outcome measures in the first year of postgraduate training, using data from
      947 graduates of Wright State University School of Medicine from 1980 through
      1991. The medical school variables were preclinical grade-point averages (GPAs),
      clerkship GPAs, scores on the National Board of Medical Examiners (NBME) Part I
      examination, and NBME Part II scores. The outcome measures were NBME Part III
      scores and physician supervisors' ratings of clinical competence in residency.
      The medical school academic variables correlated between .46 and .71 with NBME
      Part III scores and between .20 and .30 with the physician supervisors' ratings.
      R2 values for NBME Part III scores and physician supervisors' ratings were .51
      and .10. Chi-square analysis using factor-analysis-derived variables showed that
      top-quarter and bottom-quarter achievers in medical school were highly unlikely
      to change positions whether the graduate outcome measure was physician
      supervisors' ratings or NBME Part III scores.

PMID- 8141857
TI  - Active management of prolonged pregnancy.
AB  - OBJECTIVES: We assessed perinatal morbidity and mortality of prolonged
      pregnancies (> or = 294 days) compared with those of term gestations. We also
      evaluated the impact of induction of labor compared with spontaneous onset of
      labor. STUDY DESIGN: This observational study included consecutive cases treated
      at Chicago Lying-In Hospital from July 1980 to December 1984. Complications,
      presence of meconium, indications for cesarean section, mode of delivery,
      perinatal morbidity (and mortality), meconium aspiration, and duration of labor
      were compared with those in the total hospital population, in infants weighing >
      or = 2500 gm, and within prolonged gestation groups; spontaneous onset and
      induced ("active management") labors were also compared. The chi 2 analysis was
      used. RESULTS: Of 12,930 deliveries there were 707 prolonged gestations (5.5%)
      and 10,698 with infants > or = 2500 gm. Among the prolonged gestations 67% were
      in multiparous women and 33% in primiparous women. Labor started spontaneously in
      62%, and 38% underwent induction; the overall cesarean section rate was 17% with
      similar indications in both spontaneous onset and induction groups. Meconium was
      present in 34%; it was present in 23% of inductions, which is fewer (p < 0.01)
      than among those with spontaneous onset of labor (40%). Also there were fewer
      depressed neonates at 5 minutes (p = 0.03) among inductions. Meconium aspiration
      was seen in 24, with nine deaths. The perinatal mortality was 14 per 1000
      (corrected 12.7/1000), significantly more than in the general population. Among
      those with spontaneous onset of labor it was 20.5 per 1000; there were no deaths
      among inductions. Postpartum maternal morbidity was 16% among cesarean sections
      and 4% among vaginal deliveries. CONCLUSIONS: Prolonged gestation has a high
      perinatal morbidity and mortality rate. All perinatal deaths were observed among
      patients whose labor started spontaneously. "Active management" (induction at 42
      weeks) did increase the primary cesarean section rate compared with that of the
      general obstetric population; it did not do so among prolonged gestations and
      prevented perinatal deaths in this group. From this experience an active approach
      seems justified.

PMID- 8141858
TI  - Mohs micrographic surgery.

PMID- 8141859
TI  - Endometrioma: analysis and sonographic classification of 51 documented cases.
AB  - We analyzed 51 proven cases of endometrioma and characterized the sonographic
      patterns as purely cystic, cystic with few septations or minimal debris, complex
      combinations of cystic and solid elements, and largely solid. In this series, 30%
      were purely cystic, 62% showed various degrees of complexity with septation or
      debris, and 8% appeared essentially solid. The broad spectrum of patterns is in
      keeping with the evolutionary process of endometriomas, which follow essentially
      the same transitions from homogeneous gelatinous (cystic) through partially
      resolved (liquified) complex and ultimately returning to nearly purely cystic, as
      do hematomas. The average diameter of endometriotic masses was 6.1 cm (range, 2.0
      to 20.0 cm), and the average age of the patients at diagnosis was 31.3 years
      (range, 15 to 45 years). The diversity of sonographic appearance, the span of
      essentially all the child-bearing years, and the presence of endometriomas
      without a history of infertility or dysmenorrhea (and even after hysterectomy)
      keep this entity a constant differential diagnostic consideration in
      sonographically identified pelvic masses. We believe this to be the largest
      documented series of sonographically identified endometriomas in the literature.

PMID- 8141860
TI  - Alcoholics with eating disorders: prevalence and clinical course. A study from
      Japan.
AB  - Investigation of the prevalence of eating disorders among a large sample of
      Japanese alcoholics admitted for hospital treatment revealed a strong association
      between eating disorders and alcohol abuse and alcohol dependence among young
      women. That association was not apparent in young men. The results of this study
      of the clinical courses of eating disorders and alcohol abuse and alcohol
      dependence suggest that women with eating disorders, especially bulimia nervosa,
      are at high risk of becoming alcoholic.

PMID- 8141861
TI  - Continuous spinal anesthesia: where do spinal catheters go?
AB  - The purpose of this study was to investigate the incidence of technical problems
      encountered when performing continuous spinal anesthesia and the influence of
      catheter tip position on block height following injection of a hypobaric spinal
      anesthetic. Twenty-nine elderly patients undergoing hip surgery were studied.
      Lumbar puncture was performed with an 18-gauge Tuohy needle at the L3-4 (or L2-3)
      interspace. Threading was defined as easy if a 20-gauge catheter was inserted on
      the first try, 3-4 cm cephalad. Threading was considered difficult if cephalad
      insertion of the catheter was impossible on the first try; the Tuohy needle was
      then rotated with its bevel facing caudally, the catheter inserted for 1-2 mm,
      and the needle turned back cephalad together with the catheter partially
      threaded, for further cephalad insertion up to 4 cm. All patients received 7.5 mg
      of hypobaric bupivacaine or tetracaine in the lateral decubitus position and
      sensory levels were determined by pinprick. After surgery all catheters were
      injected with radiographic dye and examined by radiograph for verification of
      position. The determination of the level of lumbar puncture was falsely judged in
      59% of cases, the puncture being performed 1 or 2 spaces higher than assumed.
      Although threading difficulties were encountered in 4/28 cases, there was a 100%
      success rate in catheter insertion. One catheter displacement into the epidural
      space was noted. Twenty of twenty-eight catheters took a cephalad direction, 6
      remained coiled in a horizontal position, and 2 took a caudal direction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8141862
TI  - Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5%
      lidocaine.

PMID- 8141863
TI  - LMA and the stylet: a source of new strength for the old mask.

PMID- 8141864
TI  - The use of nonhuman animals in speech, language, and hearing research.

PMID- 8141865
TI  - Association between bovine collagen dermal implants and a dermatomyositis or a
      polymyositis-like syndrome.
AB  - OBJECTIVE: To determine whether an excess incidence of dermatomyositis or
      polymyositis or both exist in patients treated with injectable bovine collagen
      implants and to characterize the clinical picture. DESIGN: Historical cohort
      study (July 1980 through June 1988). PATIENTS: Patients were identified from
      personal experience or adverse reaction reports received by the manufacturer.
      SETTING: An 8-year period in the United States during which approximately 345,000
      patients received implants. RESULTS: Eight patients with dermatomyositis and an
      additional patient with polymyositis were identified from approximately 345,000
      patients receiving injectable bovine collagen implants from July 1980 through
      June 1988. The nine patients with dermatomyositis or polymyositis were diagnosed
      an average of 6.4 months (range, 0.7 to 24.9 months) after collagen implant or
      skin test exposure or both. Eight of the nine patients had a delayed-type
      hypersensitivity response at the test or treatment sites or both, and five of six
      patients tested were found to have increased serum antibodies to collagen.
      Compared with the general population, the incidence of dermatomyositis or
      polymyositis among collagen-treated patients was statistically increased
      (standardized incidence ratio, 5.05; 95% CI, 2.31 to 9.59; P < 0.0001). A similar
      analysis of the eight dermatomyositis case patients produced a standardized
      incidence ratio of 18.8 (CI, 8.1 to 37.0; P < 0.0001). Using a Monte Carlo
      simulation, an interval of 6.4 months or less from exposure to onset of disease
      was found to be an extremely rare event, occurring less than 72 times per one
      million simulation trials (CI, 57 to 91). CONCLUSIONS: Because these data suggest
      that an immunologic response to bovine type I or type III collagen or both caused
      this dermatomyositis or polymyositis-like syndrome, the risks versus benefits for
      the cosmetic use of collagen implants should be reassessed.

PMID- 8141866
TI  - Analysis of coronary angioplasty practice in the United States with an insurance
      claims data base.
AB  - BACKGROUND: Coronary angioplasty is frequently performed in the United States,
      with more than 300,000 procedures in 1990. Despite the high rate of use of the
      procedure, there have been few studies addressing practice patterns. METHODS AND
      RESULTS: From a private insurance claims data base of 5.4 million individuals, a
      total of 2,101 patients who underwent coronary angioplasty during 1988-1989 were
      identified. Using their 4,578 hospital admission records and 87,578 outpatient
      claim records, with an average follow-up of 332 +/- 182 days, we compared
      patients' outcomes and charges according to whether they had an exercise stress
      test before the procedure, by sex, by region of the country, and by whether the
      angioplasty was performed in an institution with a training program. Only 29% of
      the study cohort had exercise testing before angioplasty; patients in the West (p
      = 0.001), those undergoing multivessel angioplasty (p = 0.00001), and those whose
      procedures were performed at sites with training programs (p = 0.04) were more
      likely to have a screening test, whereas women (p = 0.008) and those with a
      recent myocardial infarction (p = 0.00001) were less likely to have a screening
      test. The average length of stay for patients without myocardial infarction as a
      primary diagnosis was 5.6 days, with a total hospital charge of $15,027. In
      follow-up, 15.1% had coronary artery bypass surgery and 15% had at least one
      additional angioplasty procedure; the average follow-up charges were $4,879.
      Charges varied according to sex, region of the country, and academic status of
      the angioplasty institution. Certain outcomes showed variation by region of the
      country and academic status of the angioplasty institution. CONCLUSIONS: The
      relative lack of an objective definition of myocardial ischemia and the marked
      variability of use of procedures according to geographic region suggest the need
      for further implementation of established guidelines.

PMID- 8141867
TI  - Re: Percutaneous management of urolithiasis during pregnancy.

PMID- 8141868
TI  - Does supplementation of diet with 'fish oil' reduce blood pressure? A meta
      analysis of controlled clinical trials.
AB  - BACKGROUND: Several lines of evidence suggest that supplementation of diet with
      omega-3 polyunsaturated fatty acids (omega-3 PUFA), commonly referred to as fish
      oils, may reduce blood pressure (BP). However, most clinical trials of omega-3
      PUFA supplementation have been of insufficient size to detect relevant BP
      changes. METHODS: We conducted a meta-analysis of 17 controlled clinical trials
      of omega-3 PUFA supplementation. To estimate an overall effect of omega-3 PUFA
      supplementation on BP, we calculated the net BP change in each trial (BP delta in
      omega-3 PUFA group minus BP delta in control group), which was then weighted
      according to the inverse of the variance. RESULTS: In the 11 trials that enrolled
      normotensive individuals (n = 728), omega-3 PUFA supplementation led to
      significant reductions of systolic BP (SBP) and diastolic BP (DBP) in two and one
      trials, respectively. In the six studies that enrolled untreated hypertensives (n
      = 291), significant reductions of SBP and DBP were present in two and four
      trials, respectively. Weighted, pooled estimates of SBP and DBP change (mm Hg)
      with 95% confidence intervals were -1.0 (-2.0 to 0.0) and -0.5 (-1.2 to +0.2) in
      the trials of normotensives, and -5.5 (-8.1 to -2.9) and -3.5 (-5.0 to -2.1) in
      the trials of untreated hypertensives. In 13 of 17 studies, trial duration was
      less than 3 months. Doses of omega-3 PUFA tended to be high (average dose > 3 g/d
      in 11 trials). The magnitude of BP reduction was greatest at high BP but was not
      significantly associated with dose of omega-3 PUFA. Side effects, most commonly
      eructation and a fishy taste, occurred more frequently in omega-3 PUFA
      participants than in control participants (28% vs 13%, P < .001). CONCLUSIONS:
      Our analyses indicate that diet supplementation with a relatively high dose of
      omega-3 PUFA, generally more than 3 g/d, can lead to clinically relevant BP
      reductions in individuals with untreated hypertension. However, use of omega-3
      PUFA as antihypertensive therapy will require demonstration of long-term efficacy
      and patient acceptability of lower doses.

PMID- 8141869
TI  - Young Quebec FPs say deal to force hospital-based work sacrifices them.

PMID- 8141870
TI  - Is medical ethics lost?

PMID- 8141871
TI  - Effect of nasal dilation on snoring and apneas during different stages of sleep.
AB  - This study was designed to test the hypothesis that nasal dilation reduces
      snoring. To achieve this we performed nocturnal polysomnography, including
      measurement of snoring, in 15 patients without nasal pathology before and after
      insertion of a nasal dilator (NOZOVENT). Snoring was quantified for each sleep
      stage by recording the number of snores per minute of sleep, number of snores per
      minute of snoring time and nocturnal sound intensities (maximum, average and
      minimum). We found that nasal dilation had no effect on the number of apneas,
      hypopneas or oxygen saturation. Snoring parameters were unaffected by NOZOVENT
      during stages I, II and REM sleep, but were all significantly reduced during slow
      wave sleep. We conclude that dilation of the anterior nares in patients without
      nasal pathology has a relatively weak effect on snoring, and routine use of nasal
      dilating appliances is not recommended for treatment of snoring.

PMID- 8141872
TI  - The 31st Rovenstine Lecture. The changing horizons in anesthesiology.
AB  - Modern anesthesiology differs widely from what it was 40-50 years ago, not only
      because of what anesthesiology now involves in the operating room, but also
      because anesthesiology has expanded its horizons and activities above and beyond
      the provision of surgical anesthesia. These changes and the identity of modern
      anesthesiology are, however, but poorly understood, if understood at all, by the
      majority of laity and physicians alike. Such lack of identity, especially in the
      minds of those at the policy- and decision-making level, can only endanger the
      vitality and future of anesthesiology in an era of sweeping changes in health
      care-delivery systems. The problem of public identity of our specialty includes
      the historically correct, but, contemporaneously, all too often misleading name
      of our specialty. It is suggested that it is appropriate, at this time, to at
      least consider the potential advantages of changing the name of our specialty to,
      say, metesthesiology and metesthesiologist, to indicate that while, today, our
      specialty continues to involve operative anesthesia, it extends above and beyond
      to include a wide variety of professional activities outside the operating room
      richly rewarding to patient and practitioner alike.

PMID- 8141873
TI  - An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients
      with resected colon cancer.
AB  - OBJECTIVE: To determine the effectiveness of carcinoembryonic antigen (CEA)
      monitoring in detecting surgically curable recurrence of colon cancer. DESIGN:
      Clinical data were collected from a national surgical adjuvant trial in which CEA
      monitoring was elective. SETTING: Cancer centers, universities, and community
      clinics. PATIENTS: A total of 1216 patients with resected colon cancer, 1017
      (84%) of whom had CEA monitoring. MAIN OUTCOME MEASURES: Sensitivity and
      specificity of CEA testing for cancer recurrence and CEA-motivated diagnostic and
      surgical interventions and their end results. RESULTS: Among 417 monitored
      patients with recurrence, 59% had a preceding elevation of CEA concentration.
      Sixteen percent of 600 patients without recurrence showed a false-positive test
      result. Carcinoembryonic antigen testing was most sensitive for hepatic or
      retroperitoneal metastasis and relatively insensitive for local, pulmonary, or
      peritoneal involvement. Surgical explorations were performed in 115 patients with
      CEA elevations, and 47 recurrences, usually hepatic, were resected with curative
      intent. On the other hand, 38 patients with normal CEA concentrations and 23
      patients not monitored also underwent such resections--usually for pulmonary or
      local recurrence. Of all CEA-monitored patients, 2.3% are alive and disease free
      more than 1 year after salvage surgery (2.9% of those with CEA elevations and
      1.9% of those with no elevations). Of patients with no CEA monitoring, 2.0% are
      also alive and disease free more than 1 year after salvage surgery. CONCLUSIONS:
      Cancer cures attributable to CEA monitoring are, at best, infrequent. It is
      questionable whether this small gain justifies the substantial cost in dollars
      and physical and emotional stress that this intervention may cause for patients.

PMID- 8141874
TI  - Societies of parenteral and enteral nutrition.

PMID- 8141875
TI  - Use of antibiotics in preventing recurrent acute otitis media and in treating
      otitis media with effusion. A meta-analytic attempt to resolve the brouhaha.
AB  - OBJECTIVE: To determine the efficacy of antibiotics for prophylaxis of recurrent
      otitis media and treatment of otitis media with effusion (OME) in children. DATA
      SOURCES: MEDLINE from 1966 through April 1993, textbooks, Current Contents, and
      bibliographies of selected articles. STUDY SELECTION: Thirty-three studies
      initially identified were reviewed by three blinded reviewers assessing study
      quality and suitability for inclusion. Twenty-seven met inclusion criteria for
      the meta-analyses. DATA EXTRACTION: We abstracted quantitative data and
      calculated rate differences (RDs) using tympanometry as the preferred outcome
      measure. DATA SYNTHESIS: Nine studies of antibiotic prophylaxis of recurrent
      otitis media with 958 subjects had an RD of 0.11 (95% confidence interval [Cl],
      0.03 to 0.19) favoring antibiotic treatment. Twelve studies of short-term patient
      outcomes of OME with 1697 subjects had an RD favoring antibiotics of 0.16 (95%
      Cl, 0.03 to 0.29), while eight studies using the ear as the outcome measure with
      2052 ears studied had an RD of 0.25 (95% Cl, 0.10 to 0.40). No significant
      difference was shown between placebo and antibiotics (RD, 0.06; 95% Cl, -0.03 to
      0.14) in the eight studies of longer-term outcome of OME. Subgroup analyses by
      antibiotic grouping, duration of treatment, and duration of disease did not show
      significant differences. CONCLUSIONS: Antibiotics appear to have beneficial but
      limited effect on recurrent otitis media and short-term resolution of OME. Longer
      term benefit for OME has not been shown. The findings are limited by the failure
      of most studies to consider potential confounders and by inability to identify
      groups of patients most likely to benefit.

PMID- 8141876
TI  - Spasticity: pathophysiology and management.

PMID- 8141877
TI  - A predictive model for aggressive non-Hodgkin's lymphoma.
AB  - BACKGROUND: Although many patients with intermediate-grade or high-grade
      (aggressive) non-Hodgkin's lymphoma are cured by combination chemotherapy, the
      remainder are not cured and ultimately die of their disease. The Ann Arbor
      classification, used to determine the stage of this disease, does not
      consistently distinguish between patients with different long-term prognoses.
      This project was undertaken to develop a model for predicting outcome in patients
      with aggressive non-Hodgkin's lymphoma on the basis of the patients' clinical
      characteristics before treatment. METHODS: Adults with aggressive non-Hodgkin's
      lymphoma from 16 institutions and cooperative groups in the United States,
      Europe, and Canada who were treated between 1982 and 1987 with combination
      chemotherapy regimens containing doxorubicin were evaluated for clinical features
      predictive of overall survival and relapse-free survival. Features that remained
      independently significant in step-down regression analyses of survival were
      incorporated into models that identified groups of patients of all ages and
      groups of patients no more than 60 years old with different risks of death.
      RESULTS: In 2031 patients of all ages, our model, based on age, tumor stage,
      serum lactate dehydrogenase concentration, performance status, and number of
      extranodal disease sites, identified four risk groups with predicted five-year
      survival rates of 73 percent, 51 percent, 43 percent, and 26 percent. In 1274
      patients 60 or younger, an age-adjusted model based on tumor stage, lactate
      dehydrogenase level, and performance status identified four risk groups with
      predicted five-year survival rates of 83 percent, 69 percent, 46 percent, and 32
      percent. In both models, the increased risk of death was due to both a lower rate
      of complete responses and a higher rate of relapse from complete response. These
      two indexes, called the international index and the age-adjusted international
      index, were significantly more accurate than the Ann Arbor classification in
      predicting long-term survival. CONCLUSIONS: The international index and the age
      adjusted international index should be used in the design of future therapeutic
      trials in patients with aggressive non-Hodgkin's lymphoma and in the selection of
      appropriate therapeutic approaches for individual patients.

PMID- 8141878
TI  - Uremic pericarditis in chronic renal failure: nursing implications.
AB  - Cardiovascular complications are the leading cause of death in patients with
      chronic renal failure. Pericardial disease is among the first recognized
      manifestations of uremia. This article explores the pathophysiology of uremic
      pericarditis, assessment of chronic renal failure patients at risk for developing
      pericarditis, and major complications of pericarditis. Current treatment
      modalities and nursing care for the patient with uremic pericarditis are
      included.

PMID- 8141879
TI  - Prognostic significance of the initial electrocardiographic pattern in a first
      acute anterior wall myocardial infarction.
AB  - The availability of potent, but potentially dangerous, types of reperfusion
      therapy for acute myocardial infarction (AMI) has forced us to refine our tools
      for early and accurate diagnosis and for early risk stratification of patients
      with evolving AMI. The estimation of risk has to be made shortly after admission,
      when only the history, physical examination, and the ECG are available. This
      study was undertaken to compare in-hospital mortality with different patterns of
      the ECG obtained at admission in 147 consecutive patients with an evolving first
      AMI of the anterior wall. By using a new classification of the admission ECG, it
      was possible to divide the patients into 3 groups: (1) group A contained 12
      patients with tall peaked T waves in the involved leads, without ST segment
      elevation; (2) group B comprised 77 patients with abnormal T waves and ST
      elevation, but without major changes in the terminal portion of the QRS complex;
      and (3) group C comprised 58 patients with abnormal T waves, ST elevation, and
      distortion of the terminal portion of the QRS. The mortality was 0, 3 percent,
      and 29 percent in groups A, B, and C, respectively (chi 2 = 22.91; p = 0). By
      using a logistic regression model, it was found that the initial ECG pattern
      alone is a strong predictor of in-hospital mortality in patients with an evolving
      anterior wall AMI. The predicted probabilities of death in groups A, B, and C are
      0.0016, 0.025, and 0.29, respectively. This simple classification of the initial
      ECG pattern in patients with a first AMI of the anterior wall may enable the
      differentiation of patients with low in-hospital mortality (groups A and B) and
      of those with an in-hospital mortality of almost 30 percent (group C).

PMID- 8141880
TI  - The real cost of MRI in Canada.

PMID- 8141881
TI  - Gun ownership and crime.

PMID- 8141882
TI  - Acidosis and [K+].

PMID- 8141883
TI  - Penicillin-resistant pneumococci.

PMID- 8141884
TI  - Another duplication of der(14)t(8;14)(q24;q32) in a case of Burkitt's type L3
      ALL.

PMID- 8141885
TI  - Cambodian follow-up.

PMID- 8141886
TI  - A disagreement about statistical method.

PMID- 8141887
TI  - Invisibility of carers.

PMID- 8141888
TI  - Calorie-restricted weight reduction, blood pressure, and atrial natriuretic
      peptides.

PMID- 8141889
TI  - Allergy testing.

PMID- 8141890
TI  - Ectodermal dysplasia with corkscrew hairs: observation of probable autosomal
      dominant tricho-odonto-onychodysplasia with syndactyly.

PMID- 8141891
TI  - Neglecting the elderly diabetic?

PMID- 8141892
TI  - Conflicts of interest.

PMID- 8141893
TI  - Autopsy findings of primary Sjogren's syndrome with end-stage renal failure.

PMID- 8141894
TI  - Negative correlation between fasting plasma insulin and ambulatory blood pressure
      in patients on chronic hemodialysis.

PMID- 8141895
TI  - A classification system for laparoscopic hysterectomy.

PMID- 8141896
TI  - Significance of low serum ferritin levels in elderly in-patients.

PMID- 8141897
TI  - Factors which predict performance on the National Certification Examination for
      Nurse Anesthetists.

PMID- 8141898
TI  - Questions we simply should ask.

PMID- 8141900
TI  - Physician payment: fee for time.

PMID- 8141899
TI  - Race and allocation of kidneys for transplantation.

PMID- 8141902
TI  - Does this patient have sinusitis?

PMID- 8141901
TI  - Simultaneous lung infections in patients with acquired immunodeficiency syndrome.

PMID- 8141903
TI  - The impact of first-responder defibrillation.

PMID- 8141904
TI  - Prenatal ultrasound screening and perinatal outcome.

PMID- 8141905
TI  - Predictors of mortality in patients undergoing hemodialysis.

PMID- 8141906
TI  - Actual causes of death in the United States.

PMID- 8141907
TI  - Zone I retinopathy of prematurity.

PMID- 8141908
TI  - Nitric oxide homeostasis control as therapy for cardiovascular diseases.

PMID- 8141909
TI  - Hearing loss.

PMID- 8141910
TI  - Neurologic complications of heart surgery in infants.

PMID- 8141911
TI  - Osteonecrosis of the femoral heads in inflammatory bowel disease.

PMID- 8141912
TI  - Prenatal determination of fetal RhD type.

PMID- 8141913
TI  - Warm brown fat.

PMID- 8141914
TI  - Multiple system atrophy with autonomic failure and human T-lymphotrophic virus
      type I infection.

PMID- 8141915
TI  - Nitrate therapy and the development of tolerance.
AB  - The efficacy of organic nitrates in the treatment of acute episodes of angina
      pectoris is unquestioned. However, long-term use of these agents is associated
      with the development of tolerance or of reduced efficacy over time when given in
      doses or formulations that maintain therapeutic blood levels for 24-hour periods.
      Thus, the role of long-term use of nitrates in prophylactic treatment of stable
      angina has been questioned. The purpose of this brief review is to evaluate
      nitrate tolerance, a key issue in the prophylactic use of nitrates, as well as to
      review what is known about clinical rebound. These issues are discussed, and ways
      of preventing tolerance development are explored. Intermittent therapy involving
      a dose-free interval during each 24-hour period helps prevent tolerance.

PMID- 8141916
TI  - Tendon transposition in the surgical management of a soft tissue sarcoma of the
      limb.

PMID- 8141917
TI  - Proceedings of the 12th annual conference of the Japanese Society for Biomedical
      Research on Alcoholism. Yokohama, Japan, 27 April 1992.

PMID- 8141918
TI  - New strategy for detection of ALDH2 mutant.
AB  - Genetic polymorphism of the ALDH2 gene was analysed according to a new technique
      designated as amplification created restriction site (ACRS). A restriction site
      for the enzyme (Mbo II) was artificially created in the amplification product
      using an oligonucleotide primer possessing one mismatched base. Analysis using
      ACRS technique concerning 41 healthy controls and 63 alcoholics with liver
      diseases confirmed that the ALDH2 mutant was significantly lower in alcoholics
      than in healthy controls.

PMID- 8141919
TI  - Gender-related differences in the inhibitory effect on liver regeneration in
      alcohol-treated rats: study of polyamine metabolism.
AB  - We studied gender-related differences in the effect of a single dose of ethanol
      (EtOH) on liver regeneration following partial hepatectomy in male and female
      rats by determining polyamines and their related enzymes. When rats were orally
      treated with EtOH at 3 g/kg 1 hr before partial hepatectomy, liver ornithine
      decarboxylase (ODC) activity at 4 hr post-hepatectomy was found to be lower in
      EtOH-treated female than male rats (51% vs. 42%, P < 0.01). Although no EtOH
      effect was observed on spermidine acetyltransferase (SAT) activity, female rats
      showed significantly higher values than male rats. Among intra-hepatic
      polyamines, putrescine was strongly affected by EtOH and significantly reduced in
      both male and female rats, but the effect was more marked in female than in male
      rats (88% vs. 51%, P < 0.01). With respect to spermidine and spermine, male rats
      were unaffected by EtOH, whereas EtOH-treated female rats had lower levels. The
      gender-related differences became more distinct in terms of total polyamine; the
      decrease in total polyamine due to EtOH was observed in female rats only. These
      results suggested that there was a gender-related difference in the effect of
      EtOH on liver regeneration after partial hepatectomy, with the variations in
      polyamines probably affecting the subsequent process of liver regeneration.

PMID- 8141920
TI  - Effects of ethanol and acetaldehyde on the maturation of hepatic secretory
      glycoproteins.
AB  - The effects of ethanol and acetaldehyde on the maturation and secretion of
      hepatic glycoproteins in cultured rat hepatocytes were analysed using a pulse
      chase labelling method and autoradiography following two-dimensional gel
      electrophoresis. A spot for transferrin was detected at mol. wt 77,000 and pI 5.2
      5.4 on the autoradiogram in the control culture. The spot for transferrin shifted
      to the more basic isoforms by treatment for 3 hr with monensin or tunicamycin.
      The spot for transferrin also shifted to the more basic side by treatment with
      acetaldehyde for 3 hr or by additional treatment for 3 hr following pretreatment
      with ethanol for 6 hr. However, the shift of transferrin was not observed
      following treatment with ethanol for 3 hr. These results suggest that
      glycosylation of secretory glycoproteins in the Golgi apparatus is inhibited by
      acetaldehyde, but not by ethanol itself, and that this inhibition may play an
      important role in the development of alcoholic liver disease.

PMID- 8141921
TI  - Ethanol and acetaldehyde metabolism in cultured rat hepatocytes.
AB  - In the present study, ethanol (Et-OH) and acetaldehyde (Ac-CHO) metabolism in
      primary cultured hepatocytes isolated from chronically alcohol-fed rats were
      analysed to elucidate the characteristics of the metabolism of Ac-CHO produced
      through the non-alcohol dehydrogenase (non-ADH) pathway. Dimethyl sulfoxide was
      added to the culture medium to prevent a decrease in P450 IIE1 activity. Ac-CHO
      formed in the culture medium was trapped by semicarbazide to prevent a
      reutilization of Ac-CHO by hepatocytes. The degradation rate of Ac-CHO in the
      liver was similar in alcohol and non-alcohol-treated rats. Therefore, the
      characteristic of the metabolism of Ac-CHO in the chronically alcohol-fed rats
      was not clarified in this study. The possibility that the Ac-CHO trapping by
      semicarbazide was only 70%, and that the remaining Ac-CHO was reutilized for
      oxidation in the hepatocytes, should be considered. Some method to trap Ac-CHO
      completely in the culture medium is needed to clarify the characteristics of Ac
      CHO metabolism.

PMID- 8141922
TI  - Type IV collagen and laminin contents of livers from patients with alcoholic
      liver disease.
AB  - Characteristic histological features of alcoholic liver disease (ALD) are
      pericellular and perivenular fibrosis. It has been emphasized from
      immunohistochemical studies that pericellular and perivenular fibrosis may be
      caused by the increase of type IV collagen (IV-C) and/or laminin (LM). However,
      quantitative changes of hepatic IV-C and LM contents in ALD are not well known.
      Recently, we have developed assay systems for IV-C and LM contents in liver
      biopsy specimens. In the present study, hepatic IV-C and LM contents in ALD and
      non-ALD patients were measured. Liver biopsy specimens were obtained from 36
      patients with ALD, 24 patients with non-ALD and five patients without liver
      disease. IV-C and LM contents in liver biopsy specimens were measured using the
      one-step sandwich enzyme immunoassay system for human serum IV-C and LM levels.
      Total collagen (T-C) content was also measured by the method of Leon and Rojkind.
      Hepatic IV-C, LM and T-C contents were significantly higher in all types of liver
      disease than in controls, and tended to increase with the progression of
      fibrosis. Especially in ALD, both IV-C and LM contents increased from the early
      stage, and the values in each type of ALD were significantly higher than those in
      the corresponding type of non-ALD. The ratio of IV-C or LM to T-C was also
      significantly higher in ALD than in the corresponding non-ALD. The prominent
      increases of IV-C and LM at the early stage of fibrosis may be one of the
      characteristics of collagen metabolism in ALD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141923
TI  - Effect of chronic alcohol intake on rat liver microcirculation assessed by the
      multiple indicator dilution technique.
AB  - To study the hepatic microcirculatory disturbance in alcoholic liver injury, rats
      were chronically (8-12 weeks) fed with alcohol via a gastric fistula according to
      the method of Tsukamoto and French (1986). The hepatic microcirculation was
      studied by measuring the sinusoidal volume (SV) and the apparent space of Disse
      (DS) volume using a multiple-indicator dilution technique. Both the SV and the DS
      volume were significantly decreased in the alcohol-fed rats at 8-12 weeks despite
      the absence of microscopically detectable hepatic fibrosis. Similar changes were
      noted in the alcohol-fed and control rats regarding expansion of the SV and the
      DS volume with alterations in portal pressure. However, since the volumes in the
      alcohol-fed group increased with the increase of portal pressure, they maintained
      a steady difference from the control values. These results suggested that the
      decrease of the SV and the DS volume may have been secondary to compression
      caused by steatosis and/or hepatocyte enlargement, although a possible role for
      microscopically undetectable hepatic fibrosis could not be ruled out.

PMID- 8141924
TI  - Impaired erythrocyte deformability and membrane fluidity in alcoholic liver
      disease: participation in disturbed hepatic microcirculation.
AB  - The erythrocyte deformability, membrane fluidity, mean corpuscular volume (MCV),
      and lipid compositions of erythrocyte membrane were investigated to evaluate the
      possible role in disturbed hepatic microcirculation in alcoholic liver disease.
      Erythrocyte deformability was assessed in 37 alcoholic patients and 20 normal
      subjects. Erythrocyte deformability determined by the filtration method was found
      to be decreased significantly in alcoholic patients. Erythrocyte membrane
      fluidity in alcoholic liver disease analysed by fluorescence recovery time after
      photobleaching was decreased significantly. The decrease of erythrocyte membrane
      fluidity in alcoholic patients correlated significantly with a decrease of
      erythrocyte deformability (r = -0.65, P < 0.02). The increased MCV in alcoholic
      liver disease also correlated with a decrease of erythrocyte deformability
      significantly (r = 0.652, P < 0.02). The lipid compositions of erythrocyte
      membrane were abnormal in alcoholic liver disease; the
      phosphatidylcholine:sphingomyelin ratio was increased (P < 0.001) and
      unsaturated:saturated fatty acid ratio was decreased (P < 0.01). We conclude
      that, in alcoholic liver disease, the decreased erythrocyte deformability was
      closely associated with changes of membrane fluidity and MCV. It was also
      associated with abnormalities of membrane lipid compositions. It is speculated
      that these abnormalities of erythrocytes result in further reduction of
      sinusoidal blood flow in alcoholic liver disease, and consequently disturb
      metabolic functions of the liver.

PMID- 8141925
TI  - Metabolic fate of endotoxin and blood tumour necrosis factor levels in rats with
      acute and chronic alcohol loading.
AB  - To investigate the metabolic fate of endotoxin in alcoholics and its possible
      relationship to cytokines and liver injury, we administered a low-dose
      radiolabelled endotoxin to rats given alcohol in various conditions and studied
      the organ distribution of endotoxin and measured plasma levels of tumour necrosis
      factor (TNF). In the chronic alcohol-fed rats (Lieber-DeCarli liquid diets for 6
      weeks) 3H-endotoxin was rapidly cleared by the liver and excreted into faeces.
      However, the endotoxin clearance was decreased after an acute ethanol load to
      rats (5 mg/g body wt ethanol i.p.) or in the chronic ethanol-fed rats with an
      additional 5 mg/g body wt ethanol load. Plasma TNF was not elevated in the
      control or in the acute ethanol load rats, slightly elevated in the chronic
      ethanol-fed rats and markedly elevated in the chronic ethanol-fed rats with an
      additional high-dose ethanol load. Serum GPT was elevated only in the chronic
      ethanol-fed rats with an additional high-dose ethanol. In conclusion, an
      additional administration of a high dose ethanol to chronic alcohol-fed rats led
      to decrease of endotoxin clearance and elevation of plasma TNF, which may play an
      important role in the pathogenesis of alcoholic hepatitis.

PMID- 8141926
TI  - Relationship between alcoholic liver disease and HCV infection.
AB  - The high prevalence of hepatitis C virus (HCV) markers in alcoholic liver
      cirrhosis (AL-LC) and hepatocellular carcinoma (HCC) suggests a close
      aetiopathogenic relationship between alcoholic liver disease (ALD) and HCV
      infection. In the present study, HCV markers in ALD were measured by the highly
      sensitive methods, and the changes of sequential HCV markers after abstinence in
      ALD patients were analysed in order to elucidate the effect of alcohol on HCV.
      Antibodies to HCV-related antigen were determined using the first or second
      generation test kit. HCV-RNA genomes encoding the NS-5 region were detected using
      the RT-PCR method. In the HCV-NS5 negative serum, HCV genomes of the 5'-noncoding
      region were detected using the two-stage PCR method. Titres of HCV-RNA were
      measured by multiple cyclic PCR and cDNA dot blotting. Typing of HCV genomes was
      carried out on the PCR product from the NS-5 region by slot blot hybridization
      using type-specific cDNA probes, or by restriction fragment length polymorphisms
      analysis. In alcoholic fibrosis and alcoholic hepatitis, the prevalence of HCV
      markers was low, suggesting that the main aetiological factor is alcohol but not
      HCV in these types of ALD. HCV markers were positive in the half of the patients
      with AL-LC, and in more than 80% of patients with AL-CH and AL-HCC, indicating
      that HCV infection closely relates to these types of ALD. The ratio of the K1
      type to the K2 type of HCV genomes was 4:1 in all types of NANB liver
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141928
TI  - [Special issue on "lung cancer"].

PMID- 8141927
TI  - Hepatitis C virus infection in alcoholic liver cirrhosis in Japan: its
      contribution to the development of hepatocellular carcinoma.
AB  - To determine risk factors for hepatocellular carcinoma (HCC) in Japan, we studied
      575 patients with liver cirrhosis (LC) who presented to our out-patient clinics
      in a month; 217 patients with habitual drinking with or without viral infections
      (AL-LC), 235 with hepatitis C virus (HCV) infection, 40 with hepatitis B virus
      (HB) infection, and 82 with liver diseases from other aetiologies such as primary
      biliary cirrhosis (PBC). HCC was found in 28% of AL-LC, 27% of HCV-LC, and 18% of
      HB-LC. HCV antibody examined by the second-generation HCV antibody assay (HCV II)
      was positive in 49% of AL-LC without HCC, and 84% of AL-LC with HCC. HCV was
      significantly associated with the development of HCC with an odds ratio of 1.90
      by multivariate analysis, whereas alcohol alone did not become a risk factor,
      with an odds ratio of 0.65. When both variables were combined (HCV+AL), however,
      the odds ratio was increased twice to 3.65. One-hundred and thirteen patients who
      had a history of blood transfusion more than 10 years ago were selected to assess
      the interaction between alcohol and HCV in hepatocarcinogenesis. A year-adjusted
      disease occurrence rate calculated by the Kaplan-Meyer method showed that HCV+AL
      had a significantly higher disease occurrence rate than HCV alone. These results
      suggest that although alcohol alone may not become a risk factor for HCC, it may
      potentiate the development of HCC caused by HCV. HCV+AL is considered to be the
      highest risk group; strict abstinence is necessary for these patients.

PMID- 8141929
TI  - [Broncho-pulmonary cancer: what's new? The clinician's point of view].
AB  - The severity of the prognosis of broncho-pulmonary carcinomas justifies the
      numerous studies devoted to the disease. Epidemiologic and even clinical changes
      (like the "new adenocarcinoma") are important; as are the contributions of modern
      endoscopic and imaging techniques. As for the treatment, surgery isn't the side
      treatment and great improvements have been done with chemotherapy, radiotherapy
      and with more recently new drugs or bronchoscopic technology.

PMID- 8141930
TI  - [Mechanisms of bronchial oncogenesis].

PMID- 8141931
TI  - [Stroma response in broncho-pulmonary cancer].

PMID- 8141932
TI  - [Broncho-pulmonary adenocarcinoma].

PMID- 8141933
TI  - [Cystic mucinous pulmonary tumor of borderline malignancy. Report of a case].
AB  - A cystic mucinous borderline tumor was discovered in a sixty two year old man,
      presenting as a cystic mass in the right lower lobe. A first diagnosis of
      bronchiolo-alveolar carcinoma was made on bronchial biopsies. Surgical specimen
      examination revealed a lung mucinous cystic borderline proliferation similar to
      ovary borderline mucinous tumors. Such an unusual localisation has been already
      reported. The diagnostic difficulties are reviewed.

PMID- 8141934
TI  - [Clinical staging of non-small-cell lung carcinoma].

PMID- 8141935
TI  - [Neuroendocrine lung tumors].

PMID- 8141936
TI  - [Intraepithelial mast cells in the vocal cords and nasal mucosa].
AB  - Leukocytes and mast cells have been described in the human nasal mucosa and
      epithelium of the lower airways (Bonneville 1988, Goodman and Lefrancois 1989,
      Guy-Grand 1991, Denburg 1992). In mast cells, heterogeneity of mucosal and
      connective tissue mast cells has been observed. In the present electron
      microscopic study, the epithelium of the upper airways (larynx and nose) of
      patients, suffering from chronic laryngitis, was examined with special regard to
      intraepithelial mast cells. Numerous mast cells were found in the stratum
      spinosum of the true vocal cords showing extensive elongated surface folds that
      had little contact to epithelial cells. Desmosomes were absent. Mucosal mast
      cells are characterised by four types of membrane-bounded granules, whereas
      serosal mast cells only showed two different types of granules and resembled
      blood basophiles. Migration of connective tissue mast cells into the epithelium
      could not be observed. According to our findings, mucosal and serosal mast cells
      belong to different cell lines.

PMID- 8141937
TI  - [Nasal mucociliary transport time and ciliary beat frequency in healthy probands
      and patients with sinusitis].
AB  - The mucociliary system is an important defence mechanism of the respiratory
      tract. It depends on the interaction between cilia and mucus. To evaluate the
      value of the saccharin test and a photoelectrical in-vitro method for measurement
      of ciliary beat frequency for clinical routine diagnosis, we studied twenty
      patients suffering from acute sinusitis (aged 19-64) and twenty healthy non
      smokers (aged 19-50). The nasal mucociliary transport time of saccharin was
      significantly higher (p < or = 0.01) and the ciliary beat frequency was
      significantly lower (p < or = 0.001) in patients with acute sinusitis, compared
      to normals. There was no correlation between nasal mucociliary transport time and
      ciliary beat frequency in patients with acute sinusitis (r = 0.21) and in healthy
      non-smokers (r = -0.37). Nasal mucociliary transport time of saccharin and
      photoelectrical in-vitro method for measurement of ciliary beat frequency measure
      different aspects of the mucociliary system. They are complementary. Both methods
      can be carried out together in routine diagnosis.

PMID- 8141938
TI  - [Haller's cells: morphologic evaluation and clinico-surgical relevance].
AB  - Ethmoidal cells that have developed into the floor of the orbit or into the roof
      of the maxillary sinus, respectively, are known as Haller's cells. 528 patients,
      in whom functional endoscopic sinus surgery was performed, were explored
      regarding the presence of Haller's cells. 43 patients presented with Haller's
      cells at least on one side (8.14%). CT scans of these patients were evaluated
      morphometrically measuring the dimensions of the Haller's cells as well as of the
      maxillary sinus. Further anatomical variations of the paranasal sinuses (concha
      bullosa, supraorbital cell, agger nasi cell) and the keros type of the ethmoid
      sinus roof were seen. A highly significant difference could be demonstrated
      between the incidence of Haller's cells in men (4.9%) and women (11.9%). For the
      first time it was possible to demonstrate a frequency distribution between
      Haller's cells deriving from the anterior ethmoidal cells (88%) and those
      originating from the posterior ethmoidal cells (12%). In 56% Haller's cells were
      opacified on CT-scan showing a mucosal swelling respectively a retention of
      secretion during endoscopic surgery.

PMID- 8141939
TI  - [Does the alveolar process of the maxilla always disappear after tooth loss?].
AB  - The existence of the alveolar process depends on the development of teeth. In
      edentulous maxillae, the alveolar process disappears in general in the region of
      incisives, canines and eventually premolars, but it persists in over 80% of cases
      in the region of molars. The persistence of the alveolar process correlates with
      the pneumatisation of the alveolar process by the alveolar recess of the
      maxillary sinus. The sinus may invade the whole alveolar process or only part of
      it so that in its lower part a thicker bone layer persists. Very rarely the
      alveolar process disappears completely with the loss of teeth. The deepest recess
      of the maxillary sinus corresponds to the level of the zygomatic process i.e. to
      the region of the first and second molar teeth.

PMID- 8141940
TI  - [Rhinoresistometry--a further development of rhinomanometry].
AB  - The methods of rhinological diagnostics available today are not sufficient for
      every functional aspect in modern therapeutic strategies. We developed active
      anterior rhinomanometry to rhinoresistometry, in order to improve diagnostic
      methods. We created a new software for calculation and graphic presentation. The
      program shows nasal resistance in relation to airflow. It is also possible to see
      whether the nasal airflow is laminar or turbulent depending from the degree of
      flow. Rhinoresistometry can measure the hydraulic diameter as a suitable value
      for nasal patency in nasal airflow and lambda as a parameter for the degree of
      turbulences. The method allows new views into the physiology and pathophysiology
      of nasal breathing and has been applied successfully in clinical practice.

PMID- 8141941
TI  - [Evaluation of nasal patency].
AB  - The subjective estimation of nasal breathing, the flow in anterior
      rhinomanometry, nasal peak flow and the results of acoustic rhinometry have been
      investigated in 30 patients before and after decongestion of the nasal mucosa.
      The aim of this study was to compare the different methods in view of their
      results. The effect of decongestion can be seen in all methods. A regression
      analysis showed no significant correlation between these methods. We found the
      best correlation between subjective estimation and the flow in anterior
      rhinomanometry at 75 Pa on the side of the better flow. The decisive drawback of
      the acoustic rhinometry is the fitting between nosepiece and nostril. Because of
      the influence of extranasal factors on the results of the peak flow measurement,
      anterior rhinomanometry seems to be the most reliable method to assess nasal air
      flow.

PMID- 8141942
TI  - [Model studies of nasal turbinate surgery].
AB  - The improvement of nasal air flow often requires, in addition to septoplasty,
      surgery of the turbinates. In order to broaden our knowledge of the influence of
      turbinate surgery on nasal function, the authors investigated nasal models with
      different lateral walls by visualisation of flow patterns and rhinoresistometry.
      Anterior turbinoplasty and turbinectomy reduce the nasal resistance to air flow,
      but the respiratory function of the nose deteriorates. As the result of these
      experiments, a trimming of hyperplastic turbinates must create a normal shape of
      lateral nasal wall, because the respiratory function is based on nearly regular
      narrow cavities.

PMID- 8141943
TI  - [Pre-auricular angiomyxoma in a child].
AB  - Myxomas are rare benign tumours in adolescents and adults with a predominant
      manifestation in the region of the maxillary and mandibular bone. A case of a
      cystic, slowly growing tumour in the right preauricular region is presented.
      During operation the tumour was completely encapsulated by connective tissue and
      showed a lobular shape on the cut surface with small cystic cavities.
      Histologically a myxomatous tissue was seen with a prominent and reticular
      capillary system like an angiomyxoma. The pathogenesis remains unclear. The
      definite diagnosis is established by histology. Histological and
      immunohistochemical differentiation between different benign mixed tumours should
      include myxomatous neurinomas and lipomas as well as myxomatous transformed
      histiocytomas. Surgery is the treatment of choice. After a follow-up for more
      than two years the patient is free from clinical symptoms.

PMID- 8141944
TI  - [Mesenchymal chondrosarcoma of the maxilla].
AB  - Mesenchymal chondrosarcoma is a variant that shows some peculiarities in
      comparison with classical chondrosarcomas. On the basis of a case report on a
      young man with a mesenchymal chondrosarcoma of the maxilla, the clinical
      symptomatology and diagnostics, morphological findings and actual therapy are
      discussed. In addition, problems of differential diagnosis are also discussed.

PMID- 8141945
TI  - [Nicotine concentrations in the palatine tonsil, uvula mucosa and septum
      cartilage of smokers--a pilot study].
AB  - The concentrations of nicotine were determined via radioimmunoassay in the
      palatine tonsils (n = 22) and in the mucosa of the uvula (n = 5) of eleven male
      smokers, and in the nasal septal cartilage of four other smokers. The same
      tissues of five nonsmokers served as controls. The mean values of the nicotine
      concentrations were 77 ng/g for the tonsils (level of serum: 151 ng/g), 114.5
      ng/g for the mucosa of the uvula (level of serum: 215 ng/g) and 36 ng/g for the
      septal cartilage (level of serum: 97 ng/g). There was no nicotine in the tissues
      and serum of the control group. The correlations between the nicotine
      concentrations of the three tissues and the levels of the serum were significant.
      Another significant correlation was found between the nicotine level of the serum
      and the daily consumption of cigarettes of the eleven patients on whom
      tonsillectomy had been performed. These concentrations of nicotine in the three
      types of tissue and in serum appear to be high after an interval of twelve hours
      non-smoking. With gas-chromatography/mass-spectrometry also unchanged nicotine
      was found in the tonsils which is considered to be the damaging substance of
      tobacco.

PMID- 8141946
TI  - [Tracheostoma treatment after laryngectomy].

PMID- 8141947
TI  - [Psychological management of patients with tumors].

PMID- 8141948
TI  - [Current status of laser surgery in the area of the soft palate and adjoining
      regions].
AB  - The amount of different clinically available lasers is increasing. The ENT
      surgeon can therefore use the best laser for the planned operation. As the
      resources of the hospital do not increase with the laser technology, a decision
      has to be made whether in addition to the universal CO2-laser other types must be
      acquired and which type is best. This paper presents the characteristics and
      typical tissue interactions of several lasers for the area of the soft palate.
      Typical operative examples are shown, e.g. partial resection of the soft palate
      in patients with bronchopathy and sleep apnoea syndrome, tonsillectomy,
      tonsillotomy and adenotomy in adults.

PMID- 8141949
TI  - [Recent findings on the etiology and pathogenesis of cholesteatoma--an overview].

PMID- 8141950
TI  - [Microsurgical procedures in reconstructive otorhinolaryngologic surgery].
AB  - For reconstruction of bony and soft tissue defects numerous free flaps are
      available to the head and neck surgeon. Different tissues, as from skin, mucosa,
      fat, muscle or bone can be transferred by microvascular transplantation.
      Microvascular tissue transfer has completely replaced tissue transfer from
      distant donor sites and in daily routine now competes with pedicled tissue
      transfer. Most of the reconstructive problems can be solved by using a limited
      number of reliable and versatile flaps, e.g. forearm, scapular, latissimus dorsi
      and jejunal flap. The scapular flap offers advantages in reconstruction of
      extensive cervical soft tissue defects. In facial dysplasia, facial contours may
      be restored satisfactorily with a completely deepithelialised scapular flap.
      Facial soft tissue defects are closed most satisfactorily by cutaneous forearm
      flaps. Cutaneous scapular and forearm flaps also can be used as osteocutaneous
      flaps and are thus suitable for closure of additional mandibular and maxillary
      bony defects. The closure of large penetrating defects of the cheek is best
      achieved by the folded forearm flap. It also provides an ideal replacement of
      intraoral mucosa. For reconstruction of the tongue and the floor of the mouth the
      musculocutaneous latissimus dorsi flap generally shows the best functional
      results. In oro- and hypopharyngeal lining and replacement of the cervical
      oesophagus the jejunal transplant is superior to the forearm flaps.

PMID- 8141951
TI  - [Non-squamous epithelial malignancies of the larynx with special reference to MRT
      diagnosis].
AB  - Non-squamous malignancies of the larynx are extremely rare, usually subsurface in
      origin and mostly diagnosed only in an advanced stage. Two cases representative
      of this group are described, namely, an adenoid cystic carcinoma and a
      pleomorphic rhabdomyosarcoma. The clinicopathological data of these unusual
      tumours are presented and the current therapeutic modalities discussed. The
      diagnostic value of MRI with contrast medium is emphasised by demonstrating an
      otherwise not recognised far advanced tumour stage. The pleomorphic
      rhabdomyosarcoma was also examined via electron microscopy.

PMID- 8141952
TI  - [Fine mesh metal endoprostheses for treatment of extensive cervical and
      intrathoracic tracheomalacia].
AB  - The treatment of tracheal stenoses caused by tracheomalacia is mainly carried out
      by means of sleeve resection, tracheopexy with ring support or other
      tracheoplastic operative procedures. If patients cannot be treated by surgical
      operative strategies, conventional stents are usually used to dilate the trachea.
      The use of a self-expanding elastic metal prosthesis in 5 patients with tracheal
      airway obstruction caused by tracheomalacia proved to be a true alternative in
      the therapy of tracheobronchial stenoses. We report on the long term use of 5
      patients with tracheal stenoses treated by implantation of elastic metal
      wallstents. The implantation of the stents resulted in immediate improvement in
      respiratory function in all 5 patients. None of the patients experienced
      complications secondary to the stent placement. The stents were well tolerated
      (long-time follow-up 26 months). The implantation of self-expanding metal stents
      type "wallstent" seems to offer alternative possibilities for the treatment of
      tracheomalacia.

PMID- 8141953
TI  - [Surgical treatment of pediatric laryngeal stenosis in the area of the ring
      cartilage].
AB  - In the past 15 years, infants and children with laryngeal stenosis have also been
      successfully treated with laryngotracheoplasty. From 1991 to 1993 we performed a
      surgical treatment in 20 pediatric patients with subglottic stenosis. The
      anterior cricoid split procedure should always be considered in children who
      cannot be extubated before undergoing tracheotomy, especially because in case of
      failure there are no disadvantages for any further operative measurements. By
      modifying the technique described by Cotton and Seid (1980), we performed an
      endoscopically controlled anterior cricoid split in 5 children via an
      endolaryngeal approach. 4 of these patients were extubated within 10 days after
      using a nasotracheal tube for splinting the cricoid level. In 14 patients with a
      tracheostoma we used a modification of Rethi's division of the posterior lamina
      of the cricoid by the placement of a autogenous costal cartilage graft. A 6-week
      period of stenting is required for sufficient healing and stability of the
      reconstructed airway.

PMID- 8141954
TI  - [Site-specific, structural and ultrastructural characteristics of endonasal
      cavernous tissue exemplified by the inferior turbinate in man. Light and
      transmission electron microscopy study].
AB  - The cavernous tissue of the nose has been studied morphologically for now more
      than 150 years. Even though the majority of new findings was already described in
      the second half of the last century and is associated with scientists like
      Kolliker, Kohlrausch and Zuckerkandl. The vascular structures, usually described
      as "cavernous tissue" or "swell bodies" are located in different parts of the
      nasal mucosa, but mainly in the inferior turbinate. In the present paper the
      author demonstrates the results of his studies on the structure and
      ultrastructure of smooth muscle components of nasal swell bodies based on light -
      and transmission-electron microscopic findings. Light microscopic observations
      already reveal the differences in vascular wall structure between areas adjacent
      to the epithelium and those parts of the vessels located in the deeper parts of
      the tunica propria. Ultrastructural examination shows differences in size and
      density of smooth muscle cells in different parts of the cavernous tissue; it
      also demonstrates the variant appearance of the basal lamina of these muscle
      cells. The results are discussed and compared with the appropriate literature.

PMID- 8141955
TI  - [Immunohistochemical study of the neuroanatomy of the nasal turbinate in man.
      Innervation pattern of the blood vessels].
AB  - The complex vasculature of the human nasal mucosa plays an important role in the
      protection of the lower respiratory airways. It has to react to different
      external and internal stimuli and is under control of the autonomic nervous
      system. The aim of our study was to detect the precise localisation of neural
      structures in human nasal mucosa vessels under physiological conditions. Silver
      impregnation and histochemical staining techniques only allowed a partial aspect
      of autonomic innervation. Modern immunostaining methods with antibodies to neuron
      specific enolase (NSE) and S-100 protein proved to be better for the
      demonstration of nerve structures. Tissue samples were taken from inferior
      turbinates received at mucotomy in 42 patients. After fixation the samples were
      embedded in paraffin wax and cut into serial sections. Additionally frozen
      sections were performed. The immunocomplexes were visualised by the avidin-biotin
      complex (ABC) or by the alkaline phosphatase anti-alkaline phosphatase (APAAP)
      technique. A high density of S-100 and NSE immunoreactivity of neuronal and glial
      components of autonomic innervation could be demonstrated in the vessels of human
      nasal turbinates. Branching off relatively thick nerve bundles of the lamina
      propria fibres extended to the adventitia of the arteries near the periost and
      formed a periarterial nerve plexus. Fibres of this plexus supplied the smooth
      muscle tissue of the tunica media. Around veins only a few single nerve fibres
      could be demonstrated. By using immunocytochemical techniques it is possible to
      correlate the localisation of the classical neurotransmitters and multiple
      vasoactive neuropeptides with the corresponding innervation structures of the
      complex vasculature in human nasal mucosa.

PMID- 8141956
TI  - [New aspects of hearing aid fitting].
AB  - Improved methods to diagnose a hearing loss and the enormous progress in the
      development of digital and programmable hearing aids have been helpful in
      promoting the social integration of patients, even of those affected by a
      profound deafness. Besides the hearing loss, recruitment effects and alteration
      of sound can also be compensated by the new hearing aids. However, one
      precondition is that the hearing aid fitting is carried out professionally, with
      plenty of time, and including the new hearing aid fitting methods. The new
      techniques developed in our hospital to optimize hearing aid fitting are pointed
      out. Fitting should start by considering what kind of ear mould and what kind of
      different modifications are to be taken. In a great number of patients we were
      able to verify that venting combined with the insertion of a Bakke- or Libby-horn
      increases not only the subjective acceptance of the hearing aid, but also
      significantly improves speech discrimination, particularly under background
      noise. The preselection of the hearing device and precise adjustment are based on
      the hearing loss in different frequencies, involving the principle that the
      frequency response of the hearing aid and the audiogram mirror each other
      accordingly, whereas the gain of the hearing aid can not be recognised exactly
      from the audiogram. In contrast to the POGO- and the NAL-method, we recommend a
      greater amplification, especially in the higher range of frequency. Today, the in
      situ-measurement with a probe microphone is considered to be the method of choice
      for accurate frequency adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8141957
TI  - [Ondansetron--a new anesthesia relevant antiemetic?].
AB  - Ondansetron is a new selective serotonin-3-receptor antagonist which has proved
      to be effective in chemotherapy-induced nausea and vomiting. Initial studies
      evaluating the efficacy and safety of this substance for the treatment and
      prevention of postoperative nausea and vomiting yielded promising results.
      However, ondansetron's exact role in the perioperative setting still remains to
      be determined.

PMID- 8141959
TI  - [Pituitary crisis and acute renal failure--a case report].
AB  - Based on a case report, the combined occurrence of a hypopituitary crisis and
      acute renal failure (ARF) is discussed. Aetiologically, the patient's disease
      dates back to an operation on the pituitary gland 40 years previously followed by
      a panhypopituitarism. The course of the disease presented initial symptoms which
      did not suggest a hypopituitary crisis to the first physician. The patient was
      hospitalized primarily on the tentative diagnosis of encephalitis. Subsequently,
      both laboratory findings and sonography of the abdomen pointed to chronic renal
      failure. The severity of the clinical course led to the transfer of the patient
      to our hospital for haemodialysis. Examination of the soporous patient revealed
      in addition to symptoms of ARF based on ambilateral pyelonephritic
      nephrocirrhosis typical cardinal symptoms of an endocrine insufficiency. Sopor,
      serious exsiccosis, pale, cool, pigmentless skin, deficiency of axillary and
      pubic hair, gonadal atrophy, hypotonia, hypothermia, bradypnoea and bradycardia
      as well as anamnesis of the patient substantiated the tentative diagnosis of a
      hypophysical coma based on hypopituitarism, clinically dominated by
      hypothyroidism. Following an immediately launched hormone substitution in
      combination with haemodialysis the state of the patient improved. However, during
      the fifth haemodialysis cardiac arrest occurred, the cause of which was put down
      to a dysequilibrium syndrome. The cause, however, must be seen in a continuing
      stress situation, inadequate hormone substitution and in sedation with diazepam.
      After reanimation the patient was transferred to the ICU.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8141958
TI  - [Control of the placement of central venous catheters using x-ray and sonographic
      methods. A comparative controlled study].
AB  - At present there is no method available meeting all demands for accurate, simple
      and non-invasive verification of the position of central venous catheters. Using
      sonographic methods, it should be possible to verify central venous catheters
      intracardially or in the superior vena cava. We investigated whether the
      sonographic imaging of central venous catheters using a mobile echo camera
      presented an alternative to the usual control method using fluoroscopy. Since the
      investigated method has a rate of 20 to 30% false positive results and 8 to 26%
      false-negative results, it cannot be used as a routine alternative to
      fluoroscopy.

PMID- 8141960
TI  - [A case report of malignant hyperthermia in a 14-month-old boy].
AB  - A 14-month-old boy underwent bilateral antrotomies and adenotomy for bilateral
      mastoiditis. During the operation, typical symptoms of malignant hyperthermia
      (MH) became apparent. At the time of operation, pulse oximetry and capnometry
      were not possible which led to a delay in making the diagnosis. Nevertheless,
      Dantrolene, which was available in the operating theatre, was immediately
      administered. The postoperative recovery was complicated by altered cerebral
      function (inability to concentrate), muscle exhaustion and a coagulopathy which
      lasted for eleven days. A muscle biopsy of the child's father was positive for
      MH.

PMID- 8141961
TI  - [Malignant hyperthermia in swine: a study of atracurium in MH-susceptible swine].
AB  - Since muscle relaxants have been implicated in triggering malignant hyperthermia
      (MH) in MH-susceptible humans and animals, the potential of new muscle relaxants
      for triggering MH needs to be assessed in vivo in MH-susceptible pigs. The
      triggering potential of atracurium was evaluated in six MH-susceptible pigs
      during one hour infusion of a 90% blocking dose (0.4 mg/kg/h) of atracurium. The
      mean recovery time (25% to 75%) was 10.2 min and a slight increase in heart rate
      (142 to 170 beats per minute) was observed. Rectal temperature decreased slightly
      (36.4 to 35.6 degrees C) and end tidal CO2 was stable at 5.46 kpa. In this study
      atracurium did not trigger MH in susceptible pigs.

PMID- 8141962
TI  - [Anesthesia relevant features of laparoscopy--the value of capnometry].
AB  - End-expiratory capnometrical and capnographical data correspond well with blood
      carbon dioxide content. Carbon dioxide insufflation for laparoscopy results in a
      big increase in CO2 uptake as well as in respiratory deterioration due to
      positioning and increased intra-abdominal pressure. We observed 226 female
      patients during laparoscopy under general anaesthesia (midazolam-alfentanil
      atracurium or vecuronium) and artificial ventilation. Airway peak and plateau
      pressure increased by about 75% as compared to pre-insufflation levels. End-tidal
      carbon dioxide exceeded pre-insufflation levels by 2 to 19 mmHg (mean 9 mmHg).
      Both findings were correlated to speed and overall volume of CO2 insufflation.
      Major cardiocirculatory side-effects were not observed, except for rare
      bradycardia, which responded to atropine. Considerable regurgitation via or
      beneath the gastric tube occurred in 52%. Thus, general anaesthesia with
      endotracheal intubation and consistent monitoring, including capnometry, may be
      regarded as particularly safe as far as aspiration of gastric contents and
      ventilatory requirements are concerned.

PMID- 8141963
TI  - DNA triplex formed by d-A-(G-A)7-G and d-mC-(T-mC)7-T in aqueous solution at
      neutral pH.
AB  - Evidence from UV spectroscopic melting experiments indicated that the DNA
      oligonucleotide 5'-d-A-(G-A)7-G-3' (1), a repeating AG sequence found in the
      human genome, and its complement 5'-d-mC-(T-mC)7-T-3' (mC: 5-methyl-C) (2), can
      form both a triplex (with a Tm = 44 degrees C) and a duplex (with a Tm = 69
      degrees C) around physiological pH (7.2) in micromolar concentration solution
      with 0.1 M NaCl. In addition, the triplex can be detected at a pH as high as 8.4
      (Tm = 27 degrees C). The stability of the triplex formed by 1 and 2, as monitored
      by UV melting experiments, is found to increase as the pH is lowered from 8.4 (Tm
      = 27 degrees C) to 6 (Tm = 79 degrees C). However, the stability of the duplex,
      formed by 1 and 2, is found to be unchanged (the Tm is approximately 69 degrees
      C) in the same pH range. There is no triplex, as observed by UV with the
      oligonucleotides having identical sequences, when the regular cytosine base was
      used [d-C-(T-C)7-T, (3)] at a pH > 6 in the same concentration range. The
      stoichiometric ratio of the triplex formed with 1 and 2 is also found to be 1:2
      by means of a UV mixing titration study. This result suggests that the
      conformation of the triplex of 1 and 2 also involves T.A.T and mC+.G.mC base
      triads. The formation of a triplex by 1 and 2 can be observed by native gel
      electrophoresis in submicromolar conditions with magnesium ion present. The
      results of this study strongly support the theory that replacement of regular
      cytidine nucleotides by 5-methylcytosine nucleotides facilitates the formation of
      the DNA triplex at physiological pH. This could thus be used an an anti-gene
      probe via the formation of triplex under the conditions described.

PMID- 8141964
TI  - Dibenzo[a,f]quinolizines: syntheses and cytostatic activity in estrogen-sensitive
      tumor cells.
AB  - A number of methoxy-substituted 7,11b,12,13-tetrahydro-6H-dibenzo
      [a,f]quinolizines with short alkyl groups in position 6 or 12 were synthesized by
      the Bischler-Napieralski reaction using the appropriate starting material
      followed by a second ring closure reaction involving a base-generated benzyne
      intermediate. The methoxy functions in positions 2 or 3 and 9 were cleaved with
      BBr3 and the free hydroxy groups converted into the acetates. The enantiomers of
      two of these derivatives were separated by liquid chromatography on
      triacetylcellulose. Compounds with alkyl substituents bind strongly to the
      estrogen receptor except those with a cis-orientation at the central ring
      connection. The RBA values ranged from 2.2-10.8 (17 beta-estradiol: RBA = 100).
      There was no major difference in binding between the (+) and (-)-enantiomers. The
      3,9-diacetoxy-6-alkyl derivatives also showed binding affinity for the
      progesterone receptor (RBA: 1.2-3.1). The 2,9-diacetoxydibenzoquinolizines trans
      61 and -6m with ethyl and propyl respectively in position 12 strongly inhibited
      the growth of hormone-sensitive MCF-7 breast cancer cells at concentrations of
      10(-6) M and higher but were inactive in hormone-independent MDA-MB 231 breast
      cancer cells. Preliminary tests with hormone-dependent MXT mouse mammary tumors
      as model showed that these compounds have also antineoplastic activity in vivo.
      Derivative trans-61 at a dose of 20 mg/kg body weight, administered 3 times/week,
      inhibited the growth of these tumors by 78% (tamoxifen: 76% inhibition). Studies
      on the estrogenic and antiestrogenic properties of these agents in mice revealed
      that they are mixed agonists/antagonists with strong antiestrogenic activity at
      low doses but significant estrogenic effects at higher doses.

PMID- 8141965
TI  - Towards an understanding of the reactivity of E. coli R2 ribonucleotide
      reductase: a mechanistic approach to inactivation.
AB  - Five categories of reaction of the Escherichia coli R2 protein of ribonucleotide
      reductase (RNR) are defined from mechanistic studies with hydroxyurea,
      methylhydroxylamine, hydroxamic acid derivatives, long-lived organic radicals of
      which methyl viologen MV+ is a good example, hydrazine, catechol and their
      derivatives. Attention is focused on whether a particular reagent reduces only
      the tyrosyl radical (Tyr.) giving metR2, or the Tyr. and Fe(III)2 in consecutive
      steps to give fully reduced R2. In the case of hydrazine (N2H4), reduction of
      both the Tyr and Fe(III)2 occurs in a uniphasic process, while with di-imide
      (N2H2) it has already been demonstrated that the Tyr. is reduced and that
      Fe(II)Fe(III) semi-metR2 is formed. A further mechanism is observed with catechol
      and catechol-like derivatives (in this work Didox), in which there is reduction
      of the Tyr. in the first stage, followed by scavenging of the Fe(III) in the
      second. The latter offers a more permanent inactivation of R2, meriting more
      extensive study in the context of cancer drug therapy. Comparative studies on
      mouse R2 suggest that the Tyr. and Fe(III)2 of mammalian R2 forms may be more
      exposed, and as compared to E. coli R2 are approximately an order of magnitude
      more reactive.

PMID- 8141966
TI  - Synthesis, antitumor evaluation and SAR of new 1H-pyrrolo [3,2-c] quinoline-6,9
      diones and 11H-indolo [3,2-c] quinoline-1,4-diones.
AB  - New 1H-pyrrolo [3,2-c] quinoline-6,9-diones, 11H-indolo [3,2-c] quinoline-1,4
      diones and 7,8,9,10-tetrahydro-11H-indolo [3,2-c] quinoline-1,4-diones, either
      unsubstituted or methylated, have been synthesized and evaluated for antitumor
      activity. They were compared to previously described quinones which bear either a
      methoxy group or an aziridinyl substituent on the quinone nucleus in order to
      establish structure-activity relationships and to obtain compounds as active as
      aziridinylquinones, but with less toxicity. A new synthetic route was developed
      using dimethoxy derivatives as key compounds that reacted with ceric ammonium
      nitrate (CAN) to give quinones by oxidation demethylation. The biological results
      obtained in vitro indicated that: (i) new quinones display cytotoxicity higher
      than that of the methoxyquinones; (ii) unsubstituted compounds are the most
      active; (iii) methylation of the pyrrole NH has no influence on unsubstituted
      quinones, but affords inactive derivatives when the quinone nucleus is
      methylated; (iv) compared to the aziridinyl-quinones, some compounds are equally
      active or more active. Despite the cytotoxicity exerted in vitro, we could not
      find evidence for any antitumor activity of quinones against in vivo P388 murine
      leukemia.

PMID- 8141967
TI  - Decarboxylation of the antitumour drugs flavone-8-acetic acid and xanthenone-4
      acetic acid by nitrogen dioxide.

PMID- 8141969
TI  - Reproductive health: towards a brighter future.
AB  - In 1972 the World Health Organization initiated the Special Programme of
      Research, Development and Research Training in Human Reproduction. Now
      cosponsored by the United Nations Development Programme, the United Nations
      Population Fund, the World Bank and WHO, the Programme has become the main
      instrument of research in reproductive health in the United Nations system. The
      progress that has been made, and the prospects for the future, are reviewed
      below.

PMID- 8141968
TI  - Topoisomerase II mediated DNA lesions induced by acridine-4-carboxamide and 2-(4
      pyridyl)quinoline-8-carboxamide.
AB  - Acridine-4-carboxamide and 2-(4-pyridyl)quinoline-8-carboxamide represent a new
      generation of antitumor intercalators related to amsacrine (m-AMSA), a classic
      topoisomerase II-targeted drug. We examined the ability of these tricyclic
      carboxamides to induce DNA lesions that reflect the stabilization of
      topoisomerase II cleavage complexes. DNA-protein cross-links (DPC) and DNA double
      strand breaks (DSB) were assessed in mouse fibrosarcoma cells (line 935.1). DPC
      were rapidly formed and readily reversible. A bell-shape concentration dependence
      suggested a self-inhibition of DPC at higher drug levels. In isolated nuclei, DPC
      formation by 2-(4-pyridyl)quinoline-8-carboxamide required ATP and was inhibited
      by novobiocin, a topoisomerase II inhibitor. Acridine-4-carboxamide and 2-(4
      pyridyl)quinoline-8-carboxamide were also potent inducers of DSB. In contrast to
      DPC, however, DNA breaks continued to increase with drug concentration. These DSB
      were masked (presumably by non-covalently associated proteins) when analyzed by
      nucleoid sedimentation. Thus, while both DPC and DSB seemed to be topoisomerase
      mediated, at least some DSB appeared to lack the enzyme bound covalently. DNA
      lesions by tricyclic carboxamides occurred, in general, at drug concentrations
      comparable to those needed to inhibit cell survival. Also, the tricyclic
      carboxamides inhibited the catalytic activity of isolated topoisomerase II. The
      results indicate that tricyclic carboxamides interfere with the action of
      topoisomerase II. However, the mechanisms of enzyme inhibition by these drugs
      differ from the classical trapping of topoisomerase in covalent cleavage complex
      m-AMSA.

PMID- 8141970
TI  - Probing health futures.

PMID- 8141971
TI  - Chemical pollution and the elderly.

PMID- 8141972
TI  - Women's impetus in community and health development.
AB  - Women in Indonesia are playing an increasingly large part in economic activity
      and community development. Moreover, they are making a significant beneficial
      impact on the nation's health, most notably, perhaps, by helping to secure
      financial resources. The present article describes some of the ways in which
      women are working to improve the well-being of the Indonesian people.

PMID- 8141973
TI  - Good teeth without dentists.
AB  - A pilot programme of preventive dental care is reported from Zimbabwe. The target
      groups were schoolchildren, who were approached through the school health system,
      and preschool children who were reached via community-based health workers.
      Educational materials and methods were worked out in close collaboration with
      local staff. It was considered essential to anchor the programme in established
      administrative structures.

PMID- 8141974
TI  - Health promotion for Aboriginal communities.

PMID- 8141975
TI  - Community responses to AIDS.
AB  - Some examples of care in the community for people with HIV/AIDS are reported from
      Africa. Members of communities committed to fighting the AIDS epidemic cannot do
      so alone and should be given every possible help. Inadequate care favours the
      spread of HIV, as does the stigmatization of people with HIV infection and their
      families.

PMID- 8141976
TI  - Courses in environmental and occupational epidemiology.
AB  - The results of a survey are reported in which members of WHO's Global
      Environmental Epidemiology Network were asked for details of free-standing
      environmental and occupational epidemiology courses that were offered or planned
      for 1991-93 with tuition in English, French or Spanish and with places for
      persons living outside the countries concerned. Of the 126 courses on which
      information was received, 72 were open to health professionals from more than one
      discipline.

PMID- 8141977
TI  - Research as a tool for the teaching of epidemiology.
AB  - At a medical school in India, undergraduates have been given the opportunity to
      volunteer to conduct research as a means of improving their knowledge and
      understanding of epidemiology. First-year clinical students have conducted case
      control studies with emphasis on methodological detail. Second-year students have
      been involved in community-based epidemiological studies. At the intern level,
      projects related to social factors in health and disease and to health
      administration have been encouraged. This initiative has been largely welcomed by
      the students and has yielded highly encouraging results.

PMID- 8141978
TI  - Primary health care trading companies for sustainable development.
AB  - A programme of comprehensive primary health care in Zambia has been accompanied
      by the emergence of autonomous, non-profit trading and production companies that
      sell health-related goods to communities and health institutions and find markets
      for locally produced good.

PMID- 8141979
TI  - Rheumatic heart disease in Malaysia.

PMID- 8141980
TI  - An epidemiology course for the district health team.

PMID- 8141981
TI  - Yoga: a boon for health?

PMID- 8141982
TI  - Who sells drugs in rural Zaire?

PMID- 8141983
TI  - Postgraduate studies for specialist workers in substance misuse.

PMID- 8141984
TI  - A good start in life: breast-feeding in hospital.

PMID- 8141985
TI  - Contaminated food, a hazard for the very young.
AB  - Contaminated food is responsible for much diarrhoeal disease in young children,
      yet the education of mothers and care-givers about the preparation of food under
      hygienic conditions tends to be neglected.

PMID- 8141986
TI  - Children's health in the developing world: much remains to be done.
AB  - The principal causes of ill-health and mortality among children in the developing
      countries are outlined and the prospects for improvement through the provision of
      education, health services, adequate nutrition, clean drinking-water, sanitation
      and other basic needs are discussed.

PMID- 8141987
TI  - Too many births, too many deaths.
AB  - In Yemen, where both population increase and maternal mortality are exceptionally
      high, a strategy for safe motherhood has been adopted. The authors outline the
      obstacles to progress and suggest ways in which the aims of the strategy might be
      realized, with particular reference to complete reorganization of the services of
      family planning and maternal and child health care.

PMID- 8141988
TI  - Perinatal mortality in rural Tanzania.
AB  - In 1987, as part of the World Health Organization's Inter-Health Programme, we
      carried out a noncommunicable diseases survey in six rural villages in Tanzania.
      Each women completed a questionnaire, part of which was concerned with obstetric
      history, and underwent a physical examination. Our findings of unacceptably high
      perinatal mortality and abortion rates are described below.

PMID- 8141989
TI  - How can infant and perinatal mortality rates be compared internationally?
AB  - Much of the confusion surrounding international comparisons of infant and
      perinatal mortality rates could be removed if single definitions of live birth
      and fetal death were universally adopted. Suggestions as to how this might be
      achieved are made below.

PMID- 8141990
TI  - Making a start with district health libraries.

PMID- 8141992
TI  - Towards self-sufficiency in health learning materials.

PMID- 8141991
TI  - Problem-solving for better health.
AB  - An outline is given of an approach to the health-for-all goals which involves
      optimizing resource use, prioritizing people's well-being, achieving excellence
      and a measurable impact at all levels of care, and solving health problems in a
      broad developmental context.

PMID- 8141993
TI  - New programme review process for diarrhoeal disease control.

PMID- 8141994
TI  - Help for former Yugoslavia.

PMID- 8141995
TI  - Evolution of parallel beta/alpha-barrel enzyme family lightened by structural
      data on starch-processing enzymes.
AB  - The parallel beta/alpha-barrel domain consisting of eight parallel beta-sheets
      surrounded by eight alpha-helices has been currently identified in crystal
      structures of more than 20 enzymes. This type of protein folding motif makes it
      possible to catalyze various biochemical reactions on a variety of substrates
      (i.e., it seems to be robust enough so that different enzymatic functionalities
      could be designed on it). In spite of many efforts aimed at elucidation of
      evolutionary history of the present-day beta/alpha-barrels, a challenging
      question remains unanswered: How has the parallel beta/alpha-barrel fold arisen?
      Although the complete sequence comparison of all beta/alpha-barrel amino acid
      sequences is not yet available, several sequence similarities have been revealed
      by using the highly conserved regions of alpha-amylase as structural templates.
      Since many starch-processing enzymes adopt the parallel beta/alpha-barrel
      structure these enzymes might be useful in the search for evolutionary
      relationships of the whole parallel eight-folded beta/alpha-barrel enzyme family.

PMID- 8141996
TI  - Discrimination of folding types of globular proteins based on average distance
      maps constructed from their sequences.
AB  - It has been shown that probable portions which form contacts in a protein can be
      predicted by means of an average distance map (ADM) as well as regular structures
      (alpha-helices and beta-turns) defined as short-range compact regions (Kikuchi et
      al., 1988a,c). In this paper, we analyze the occurrence of those portions and
      short-range compact regions on ADMs for various proteins regarding their folding
      types. We have found out that each folding type of proteins shows characteristic
      distribution of such parts on ADMs. We also discuss the possibility of the
      prediction of folding types of proteins by ADMs.

PMID- 8141997
TI  - Strategies for selecting mutation sites for methionine enhancement in the bean
      seed storage protein phaseolin.
AB  - The complete three-dimensional structure of the bean seed storage protein
      phaseolin was generated from alpha-carbon coordinates by using molecular mechanic
      calculations. This structure was used as a template to simulate modifications
      aimed at increasing the methionine content of phaseolin. A hydrophilic,
      methionine-rich looping insert sequence was designed. Simulated mutagenesis shows
      that the insert might be accommodated in turn and loop regions of the protein,
      but not within an alpha-helix. Methionine content was also increased by the
      replacement of hydrophobic amino acids with methionine in the central core beta
      barrels of the phaseolin protein. Calculations indicated that methionine can
      effectively replace conserved or variant leucine, isoleucine, and valine
      residues. However, alanine residues were much more sensitive to substitution, and
      demonstrated high variability in the effects of methionine replacement.
      Introduction of multiple substitutions in the barrel interior demonstrated that
      the replaced residues could interact favorably to relieve local perturbations
      caused by individual substitutions. Molecular dynamics simulations were also
      utilized to study the structural organization of phaseolin. The calculations
      indicate that there are extensive packing interactions between the major domains
      of phaseolin, which have important implications for protein folding and
      stability. Since the proposed mutant proteins can be produced and studied, the
      results presented here provide an ideal test to determine if there is a
      correlation between the effects obtained by computer simulation and the effects
      of the mutations on the protein structure expressed in vivo.

PMID- 8141998
TI  - Random chemical modification of the oxygen-linked chloride-binding sites of
      hemoglobin: those in the central dyad axis may influence the transition between
      deoxy- and oxy-hemoglobin.
AB  - The features of random chemical modification are defined with reference to
      acetylation of bovine hemoglobin, which has been performed in a random manner so
      that all of the amino groups that participate in functional chloride binding
      (i.e., those that are oxygen-linked) could be identified. Random chemical
      modification, which has objectives different from those of both specific
      (selective) and extensive chemical modification, has been achieved for bovine
      hemoglobin with the mild reagent, 14C-methyl acetate phosphate; retention of
      function was demonstrated by a Hill coefficient of n = 2.2 for the modified
      hemoglobin. After removal of unmodified Hb chains, the mixture of randomly
      modified acetylated alpha or beta chains was subjected to tandem treatment with
      trypsin and chymotrypsin. Peptides were purified by HPLC and identified by amino
      acid analysis. The amount of radioactivity in the acetylated amino group of a
      purified peptide was taken as an estimate of the degree of chloride binding. For
      bovine Hb, two amino groups of the alpha-chain (Val-1 and Lys-99) and three amino
      groups of the beta-chain (Met-1, Lys-81, and Lys-103) were shown to be oxygen
      linked (i.e., to have incorporated significantly more radioactivity in the deoxy
      conformation compared to the same site in the oxy conformation). Three of these
      sites were already known chloride-binding sites [i.e., Val-1(alpha), the N
      terminus of the alpha-chain, and two sites between the 2 beta-chains of bovine
      hemoglobin, Met-1(beta) and Lys-81(beta); these findings support the conclusions
      of the random modification approach. Two other chloride-binding sites, Lys
      99(alpha) and Lys-103(beta), align the sides of the central dyad axis connecting
      the two well-known major chloride-binding sites of bovine Hb. The
      interrelationship of these five chloride-binding sites was assessed by improved
      molecular graphics. When viewed through the central dyad axis, the functional
      chloride-binding sites in the central cavity appear to be symmetrically related
      and to connect the two major chloride-binding sites. Modifiers or mutants that
      are directed at these regions in the central dyad axis may favor the deoxy
      conformation to provide a lower oxygen affinity by preventing the constriction of
      the central cavity that normally occurs upon oxygenation.

PMID- 8142000
TI  - Structural determinants of the intrinsic fluorescence emission in notexin and
      phospholipase A2 enzymes.
AB  - Fluorescence measurements of the homologous proteins, notexin and PLA2 enzymes
      from Naja naja atra, Naja nigricollis, and Hemachatus haemachatus venoms, showed
      that the wave-length of maximum emission and the quantum yield of their intrinsic
      fluorescence emission spectra were different. To verify the factors which
      affected their fluorescence characteristics, the dynamics of tryptophan residues
      in those homologous proteins were studied by quenching with acrylamide, iodide,
      and cesium. The degrees of exposure of tryptophanyl groups in notexin and PLA2
      enzymes assessed by acrylamide quenching were found to be the major factor that
      determined their fluorescence characteristics. However, the positively charged
      groups surrounding tryptophan residues of PLA2 enzymes from N. naja atra and N.
      nigricollis venoms might affect the quantum yield of their fluorophores.
      Tryptophan residues of notexin were in an environment with less fluctuation,
      which did not allow free diffusion of ionic quencher. This might render its
      tryptophan residues to fluoresce at a shorter wavelength. These results suggested
      that the structural determinants affecting the intrinsic fluorescence emission of
      homologous proteins can be easily assessed by quenching studies.

PMID- 8141999
TI  - Reactivity of cysteinyl, arginyl, and lysyl residues of Escherichia coli
      phosphoenolpyruvate carboxykinase against group-specific chemical reagents.
AB  - Calcium-activated phosphoenolpyruvate carboxykinase from Escherichia coli is not
      inactivated by a number of sulfhydryl-directed reagents [5,5'-dithiobis(2
      nitrobenzoate), iodoacetate, N-ethylmaleimide, N-(1-pyrenyl)maleimide or N
      (iodoacetyl)-N'-(5-sulfo-1-naphthylethylenediamine)], unlike phosphoenolpyruvate
      carboxykinase from other organisms. On the other hand, the enzyme is rapidly
      inactivated by the arginyl-directed reagents 2,3-butanedione and 1
      pyrenylglyoxal. The substrates, ADP plus PEP in the presence of Mn2+, protect the
      enzyme against inactivation by the diones. Quantitation of pyrenylglyoxal
      incorporation indicates that complete inactivation correlates with the binding of
      one inactivator molecule per mole of enzyme. Chemical modification by pyridoxal
      5'-phosphate also produces inactivation of the enzyme, and the labeled protein
      shows a difference spectrum with a peak at 325 nm, characteristic of a pyridoxyl
      derivative of lysine. The inactivation by this reagent is also prevented by the
      substrates. Binding stoichiometries of 1.25 and 0.30 mol of reagent incorporated
      per mole of enzyme were found in the absence and presence of substrates,
      respectively. The results suggest the presence of functional arginyl and lysyl
      residues in or near the active site of the enzyme, and indicate lack of reactive
      functional sulfhydryl groups.

PMID- 8142001
TI  - Primary structure of Beijing duck apolipoprotein A-1.
AB  - The primary structure of Beijing duck apolipoprotein A-1 was determined by
      sequencing peptide fragments derived from tryptic and endoproteinase Asp-N
      digestion of the protein, and alignment with homologous chicken apo A-1. All of
      the peptide fragments were isolated by high-pressure liquid chromatography (HPLC)
      with a Vydac C18 column using a trifluoroacetic acid (TFA) buffer system. The N
      terminus of the protein was determined to be aspartic acid by directly sequencing
      52 residues of the intact protein. The C-terminus was alanine. The protein
      contains 240 amino acid residues. By analysis of the whole protein and its
      tryptic peptides, a six amino acid (Arg-Tyr-Phe-Trp-Gln-His) prosegment was
      determined. No cross-reactivity between duck and human apo A-1 with a goat
      antiserum against human apo A-1 was found. Sequence analysis of apo A-1 of other
      species indicates that amino acid substitutions in rat are more extensive than in
      other mammals. Isoleucine residues in apo A-1 are inversely correlated to the
      homology of human to other species, except dog.

PMID- 8142002
TI  - Bovine testis acylphosphatase: purification and amino acid sequence.
AB  - Two acylphosphatase molecular forms have been isolated from bovine testis. Their
      amino acid sequence was determined. One (ACY1) consists of 98 amino acid
      residues, while the other one (ACY2) consists of 100 amino acid residues. Both
      molecular forms are N-acetylated and differ only in the amino terminus. ACY2 has
      an additional Ser-Met tail with respect to ACY1. Both ACY1 and ACY2 are organ
      common type isoenzymes and thus differ for about half of the amino acid positions
      from the previously sequenced bovine muscle isoenzyme.

PMID- 8142003
TI  - Comparative studies on S-adenosyl-L-methionine binding sites of protein N
      methyltransferases, using 8-azido-S-adenosyl-L-methionine as photoaffinity probe.
AB  - Employing a photoaffinity labeling procedure with 8-azido-S-adenosyl-L-[methyl
      3H]methionine (8-N3-Ado[methyl-3H]Met), the binding sites for S-adenosyl-L
      methionine(AdoMet) of three protein N-methyltransferases [AdoMet:myelin basic
      protein-arginine N-methyltransferase (EC 2.1.1.23); AdoMet:histone-arginine N
      methyltransferase (EC2.1.1.23); and AdoMet:cytochrome c-lysine N
      methyltransferase (EC2.1.1.59)] have been investigated. The incorporation of the
      photoaffinity label into the enzymes upon UV irradiation was highly specific. In
      order to define the AdoMet binding sites, the photolabeled enzymes were
      sequentially digested with trypsin, chymotrypsin, and endoproteinase Glu-C. After
      each proteolytic digestion, radiolabeled peptide from each enzyme was resolved on
      HPLC first by gradient elution and further purified by an isocratic elution.
      Retention times of the purified radiolabeled peptides from the three enzymes from
      the corresponding proteolysis were significantly different, indicating that their
      sizes and compositions were different. Amino acid composition analysis of these
      peptides confirmed further that the AdoMet binding sites of these protein N
      methyltransferases are quite different.

PMID- 8142005
TI  - Using periodate-oxidized nucleotide as affinity label for the nucleotide site of
      proteins.
AB  - The active site of pigeon liver malic enzyme was labeled with a fluorescent
      affinity label, the periodate-oxidized aminopyridine adenine dinucleotide
      phosphate. The modified enzyme was subjected to proteolytic digestion with
      trypsin. The resulted peptides were then separated with reversed-phase high
      performance liquid chromatography on Waters muBondapak C18 column. Two pure
      fluorescent peptides were obtained after three runs of the chromatography. The
      peptides were then subjected to automatic Edman degradation on a Beckman peptide
      sequencer and subsequently separated and identified with phenylthiohydantoin C18
      column. No sequence was obtained. The possible reasons for the failure in
      sequencing the periodate-oxidized nucleotides labeled active site peptide and
      some possible pitfalls in using these reagents were discussed.

PMID- 8142004
TI  - Purification and characterization of beta-structural domains of beta
      lactoglobulin liberated by limited proteolysis.
AB  - Incubation of beta-lactoglobulin with immobilized trypsin at 5-10 degrees C
      results in a time-dependent release of several fragments of the core domain in
      yields approaching 15%. Digests were fractionated by ion-exchange chromatography
      with a Mono Q HR 5/5 column and analyzed after disulfide reduction by
      polyacrylamide gel electrophoresis in sodium dodecylsulfate. Three fragments with
      approximate molecular weights of 13.8, 9.6, and 6.7 kD were identified. The
      fraction from ion-exchange chromatography yielding the 6.7 kD fraction after
      disulfide reduction was further characterized because it was most homogeneous and
      gave the highest yield. The C-terminal cleavage site of the 6.7 kD core fragment
      appeared to be Lys100 or Lys101 as determined by C-terminal amino acid analysis.
      The exact masses, after reduction with dithiothreitol, are 6195 and 6926 as
      determined by laser desorption mass spectrometry, corresponding to residues 48
      101 and 41-100. Prior to reduction, beta-lactoglobulin C-terminal residues 149
      162 are connected to these core domain fragments as shown by C-terminal analysis
      and mass spectrometry. Structural studies indicate that these 7.9 and 8.6 kD core
      domain fragments released by immobilized trypsin retain much of their native
      structure. CD spectra indicate the presence of antiparallel beta-sheet structure
      similar to the native protein but the alpha-helix is lost. Spectra in the
      aromatic region indicate the existence of tertiary structure. Moreover,
      structural transitions in urea are completely reversible as measured by CD
      spectra, although the extrapolated delta GDH20 and the urea concentration at the
      transition midpoint are lower than for the native protein. The core domain
      fragments also display a pH-dependent binding to immobilized trans-retinal as
      does intact protein. A single endotherm is obtained for both core domain
      fragments and native protein upon differential scanning calorimetry, but again,
      the domain is less stable as indicated by a transition peak maxima of 56.9
      degrees C as compared with 81.1 degrees C for native protein.

PMID- 8142006
TI  - Effects of Zn(II) on galactosyltransferase activity.
AB  - The enzyme beta-4-galactosyltransferase (GT) catalyzes the transfer of a
      galactosyl group from UDP-galactose to N-acetylglucosamine (GlcNAc) on
      glycoproteins. In the presence of alpha-lactalbumin (alpha-LA),
      galactosyltransferase catalyzes the transfer of galactose to glucose to yield
      lactose. It is known that, in the absence of alpha-lactalbumin, Zn(II) competes
      with Mn(II) for the same binding site(s) in galactosyltransferase, resulting in
      an increase in the apparent Michaelis constant, Km(app), for Mn(II)-activation of
      N-acetyllactosamine synthesis. In the presence of alpha-lactalbumin (i.e.,
      lactose synthase), the Mn(II)-activation is biphasic and the initial phase is
      inhibited by increasing concentrations of Zn(II). The Zn(II) inhibition of
      lactose synthase plateaus at [Zn(II)]:[alpha-lactalbumin] approximately 1:1,
      while for N-acetyllactosamine synthesis there is no plateau at all. The results
      suggest that Zn(II) binding to alpha-lactalbumin effects lactose synthase.
      Kinetically, Zn(II) induces a decrease in both the Km(app) and Vm for Mn(II),
      which results in an apparent increase, followed by a decrease, in lactose
      synthase activity at Mn(II) concentrations below saturation of the first [Mn(II)]
      binding site. Increasing Zn(II) also decreases Km(app) and Vm for both glucose
      and UDP-galactose in the lactose synthase reaction with either both Ca(II)- or
      apo-alpha-lactalbumin, further suggesting novel interactions between Zn(II)-alpha
      lactalbumin and the lactose synthase complex, presumably mediated via a Zn(II)
      induced conformational change upon binding to alpha-lactalbumin. On the other
      hand, in N-acetyllactosamine synthesis, Zn(II) only slightly effects Km(app) for
      N-acetylglucosamine and has essentially no effect on Km(app) or Vm for UDP
      galactose.

PMID- 8142007
TI  - Hemoglobins with multiple reactive sulphydryl groups: the reaction of pigeon
      hemoglobin with 5,5'-dithiobis (2-nitrobenzoic acid).
AB  - Pigeon hemoglobin has eight reactive sulphydryl groups per (tetramer) molecule,
      as determined by Boyer titration with p-chloromercuribenzoate. However, only four
      of these are titratable with 5,5'-dithiobis(2-nitrobenzoate) under the same
      experimental conditions. The time course of the reaction of pigeon hemoglobin
      with 5,5'-dithiobis(2-nitrobenzoate) is biphasic. In the pH range 6-9, the fast
      phase is between one and two orders of magnitude faster than the slow phase. For
      the fast phase, kapp, the apparent second-order rate constant, increases
      monotonously with pH. Quantitative analysis reveals that the reaction of the
      sulphydryl group responsible for this phase is coupled to the ionization of two
      groups with pKa values of 6.15 +/- 0.1 and 8.5 +/- 0.1. These pKa values are
      assigned to HisHC3(146) beta and to the CysF9(93) beta sulphydryl group,
      respectively. For the slow phase the kapp vs. pH profiles are bowl-shaped.
      Analysis reveals that the reaction of the sulphydryl group to which this phase
      may be attributed is coupled to the ionization of two groups with mean pKa values
      of 6.53 +/- 0.1 and 8.25 +/- 0.1. Examination of the structure of hemoglobin
      allows us to assign these values to HisG19(117) beta and CysB5(23) beta,
      respectively. The CysB5(23) beta sulphydryl is in the region of the molecule
      where amino acid substitutions have been found to give rise to significant
      changes in the oxygen affinity of hemoglobin [Huang et al. (1990), Biochemistry
      29, 7020-7023].

PMID- 8142008
TI  - p53 mutations in primary human lung tumors and their metastases.
AB  - In a total of 26 primary human lung tumors and 60 metastases derived from them,
      exons 5-8 of the p53 tumor suppressor gene were analyzed by single-strand
      conformation polymorphism and subsequent direct DNA sequencing of amplified DNA.
      Mutational inactivation of the p53 gene was identified in four of five squamous
      cell carcinomas, three of nine adenocarcinomas, and two of nine small-cell
      carcinomas, the overall incidence being 35%. Point mutations occurred at a
      similar incidence in exons 5-8, with a preference for G-->T transversions. In
      seven of nine cases (78%), mutations were identical in the primary tumor and all
      of its metastases, indicating that in lung tumors, p53 mutations usually precede
      metastasis and that hematogenic and lymphogenic dissemination of tumor cells to
      other tissues is not associated with a selection against p53 inactivation. In one
      case, a kidney metastasis had the same mutation as the primary squamous cell
      carcinoma, whereas a liver metastasis had no mutation, indicating heterogeneity
      of the primary lung neoplasm and selective metastasis of mutated and nonmutated
      tumor cells to kidney and liver, respectively. Only in one liver metastasis was a
      mutation identified that was neither present in the primary lung tumor nor in a
      kidney metastasis, suggesting that occasionally p53 mutations occur after
      metastatic spread.

PMID- 8142009
TI  - Constitutive AP-1 DNA binding and transactivating ability of malignant but not
      benign mouse epidermal cells.
AB  - The mouse epidermal cell line 308 contains an activated Ha-ras gene and forms
      benign papillomas when transplanted to the skin of athymic nude mice. A radiation
      associated malignant variant of this cell line, 308-10Gy5, has been isolated and
      shown to form squamous cell carcinomas in nude mice. To further examine the
      molecular events involved in malignant conversion of 308-10Gy5, we assessed the
      activator protein-1 (AP-1) binding and transactivating ability of 308 and 308
      10Gy5. In nuclear protein extracts of 308, AP-1 sequence-specific binding to an
      oligonucleotide containing a single high-affinity AP-1 binding site was induced
      by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, as determined by gel
      shift analysis. Nuclear extracts of 308-10Gy5 bound to the AP-1 oligonucleotide
      without treatment with tumor promoters. Not only was sequence-specific AP-1 DNA
      binding constitutively active in malignant versus benign tumor cells, but so was
      transactivation of a unique AP-1-responsive chloramphenicol acetyltransferase
      reporter construct, pTiCTaK. Constitutive transactivation of this AP-1-responsive
      reporter construct was observed in the malignant but not the benign tumor cells.
      Furthermore, steady-state transcript levels of the tumor-associated AP-1
      responsive genes stromelysin, urokinase-type plasminogen activator, c-jun, and c
      fos were higher in malignant 308-10Gy5 cells than in benign 308 cells. These
      results suggest that acquisition of constitutive AP-1 DNA binding and
      transactivation can result in sustained deregulation of gene expression. While
      malignant progression in keratinocytes is probably not due solely to the
      acquisition of constitutive cellular AP-1 activity, the effect of deregulated
      expression of AP-1-regulated genes, especially basement membrane-degrading
      enzymes, may be functionally related to malignant conversion.

PMID- 8142010
TI  - 2-Hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine induction of
      recombinational mutations in mammalian cell lines as detected by DNA
      fingerprinting.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant
      mutagenic heterocyclic amine in cooked foods. Two mouse tumor cell lines, BMT11
      and FM3A, were exposed to its proximate form, 2-hydroxyamino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (N-OH-PhIP). Fifty-six subclones of BMT11 and 39
      subclones of FM3A were isolated and analyzed by DNA fingerprinting. Treatment
      with 10-20 microM N-OH-PhIP gave rise to extra bands or shifted bands, but
      treatment without N-OH-PhIP did not. This suggests that mutations resulting from
      recombination were induced. The mutation frequencies were 21-53% and 22-35% for
      BMT11 and FM3A, respectively. These findings suggest that PhIP induces
      recombinational mutations.

PMID- 8142011
TI  - Screening for p53 mutations in C3H/He mouse liver tumors derived spontaneously or
      induced with diethylnitrosamine or phenobarbitone.
AB  - Distinct differences have been described in the development of C3H/He mouse liver
      tumors induced by the genotoxic carcinogen diethylnitrosamine (DEN) and by the
      nongenotoxic agent phenobarbitone (PB) in terms of pathology and the frequency of
      mutation at codon 61 of the Ha-ras oncogene. To further define the mechanisms
      involved, we screened the tumor suppressor gene p53 for mutations in exons 5, 7,
      and 8 using polymerase chain reaction (PCR)-single-strand conformation
      polymorphism (SSCP) analysis. Nearly all the mutations so far described have been
      found within these three exons. In this study a total of six spontaneous tumors,
      eight tumors induced by PB, 14 tumors induced by DEN, and five samples of normal
      liver tissue were screened, and no mutations were found in any of the tumors
      examined. The positive control, the plasmid LTRp53cG (val), had a point mutation
      in exon 5 that was detected by PCR-SSCP. Since many of the tumors were late-stage
      hepatocellular carcinomas, we concluded that mutations in exons 5, 7, and 8 of
      the p53 gene do not play an important role in the development of chemically
      induced liver tumors in the C3H/He mouse.

PMID- 8142012
TI  - Combined effects of human papillomavirus-18 and N-methyl-N'-nitro-N
      nitrosoguanidine on the transformation of normal human oral keratinocytes.
AB  - We immortalized oral keratinocytes by transfecting them with recombinant human
      papillomavirus (HPV) type 18 DNA and established three cell lines. These lines
      were morphologically different from their normal counterpart, contained
      integrated entire HPV-18 DNA, and expressed the viral E6/E7 genes. The cells
      contained less p53 protein and more c-myc mRNA than normal cells. However, they
      proliferated only in keratinocyte growth medium (KGM) containing low calcium and
      were not tumorigenic in nude mice. To test the hypothesis that tumors result from
      the combined effect of a "high-risk" HPV and chemical carcinogens in the human
      oral cavity, we exposed the immortalized cells to the chemical carcinogen N
      methyl-N'-nitro-N-nitrosoguanidine. Three chemically transformed cell colonies
      were isolated. These cells (a) proliferated well in both KGM and Dulbecco's
      modified minimum essential medium containing physiological levels of calcium; (b)
      were capable of proliferating in nude mice; (c) contained intact, integrated HPV
      18 sequences; (d) transcribed substantially more HPV-18 E6/E7, transforming
      growth factor-alpha, and c-myc than the immortalized counterpart; and (e)
      contained, like the immortalized counterpart, less wild-type p53 protein and DCC
      message. These data indicate that human oral keratinocytes can be transformed by
      sequential exposure of normal keratinocytes to a "high-risk" HPV and chemical
      carcinogens.

PMID- 8142013
TI  - The effects of bile acids on phospholipase C activity in extracts of normal human
      colon mucosa and primary colon tumors.
AB  - Phospholipase C (PLC) activity and its response to stimulation by bile acids was
      assayed in cellular extracts from 16 primary human colon tumors of various Duke's
      stages and paired adjacent normal mucosal samples. In the absence of bile acid,
      there was negligible degradation of phosphatidylinositol (PI) 1-stearoyl-2-[14C]
      arachiodonoyl by tumor or normal tissue, but the addition of deoxycholic acid
      (DCA) or taurocholic acid (TCA) resulted in concentration-dependent and time
      dependent stimulation of diacylglycerol (DAG) formation at optimal concentrations
      of 2 mM DCA and 4 mM TCA. Triton X-100 (0.125-1.0%) inhibited rather than
      enhanced the PI-degrading activity of these extracts, indicating that the
      stimulatory effects of DCA and TCA were not simply due to a detergent effect.
      Under the same assay conditions there was only a small amount of labeled
      monoacylglycerol or free arachidonic acid produced by extracts incubated in the
      absence or presence of DCA or TCA. No major differences in DAG production from PI
      were seen between paired samples of normal colon mucosa and primary colon tumors,
      in assays done in the presence of 2 mM TCA. Extracts from tumors in the distal
      part of the colon had higher activity than those from the proximal colon. This
      was also true for the extent of release of free arachidonic acid from labeled PI.
      Under the same conditions, labeled phosphatidylcholine or
      phosphatidylethanolamine did not serve as substrates for the colon mucosa or
      tumor extracts. Nor was there significant hydrolysis of the labeled DAG (1
      stearoyl-2-14C-arachidonoylglycerol) by normal colon mucosa or tumor extracts, in
      the absence or presence of DCA or TCA. On the other hand, a low level of DAG
      lipase activity was detected in the presence of Triton X-100. These findings
      provide the first evidence that normal human colon mucosa and primary colon
      tumors contain a PI-specific PLC activity that is markedly stimulated by bile
      acids. Our results also suggest that bile acids may enhance colon carcinogenesis
      by acting on this enzyme system, thereby influencing signal transduction pathways
      in the target cells.

PMID- 8142014
TI  - Mutation and altered expression of p53 genes in experimental rat bladder tumor
      cells.
AB  - p53 genes were analyzed for mutations and expression in a series of 24 tumors or
      hyperplastic lesions of the urinary bladder induced in F344 rats by carcinogen
      treatment. Of these, 18 were analyzed as short-term urothelial cultures.
      Polymerase chain reaction-single-strand conformation polymorphism analysis and
      DNA sequencing were used to detect alterations in p53 genes or cDNAs, and the
      relative amounts of p53 protein per cell were estimated by immunohistochemical
      staining. Missense substitutions were found in the exon 5-9 region of two of five
      cell cultures analyzed from lesions induced by the bladder carcinogen N-butyl-N
      (4-hydroxybutyl)nitrosamine. One of these was a papillary nodular hyperplasia,
      indicating that p53 mutations can be present in low- as well as high-stage/grade
      bladder lesions. p53 mutations were not found in the exon 5-9 region in cells of
      any of eight bladder lesions induced by N-[4-(5-nitro-2-furyl)-2-
      thiazoly]formamide (FANFT), including five transitional cell carcinomas (TCCs),
      or either of two TCCs induced by N-methylnitrosourea. Two of nine TCCs induced by
      the N-glucuronide of N-hydroxy-2-aminofluorene were found to have p53 mutations.
      One of these was evidently altered by three genetic events: a missense
      substitution in exon 8, a nonsense mutation in exon 6, and silencing of the
      "nonsense" allele (i.e., only the p53 missense mutation was detected).
      Immunohistochemical analysis with monoclonal antibody PAb240 (which
      preferentially binds to mutant p53 protein) detected p53 antigen only in those
      samples in which missense p53 mutations were found. With monoclonal antibody
      PAb421 (which detects mutant and wild-type p53), p53 antigen was also detected in
      cells from F542, a bladder tumor induced by FANFT in which no p53 mutations were
      found. Northern blot hybridization analysis showed that p53 transcripts were
      elevated twofold to threefold in several cases, including F542, suggesting that
      constitutive overexpression of wild-type p53 may occur in some bladder
      neoplasias. These data support the view that p53 may be involved in multiple rate
      limiting steps in neoplastic transformation and may be a continuing target during
      bladder carcinogenesis. The data also contribute to evidence that certain
      chemical carcinogens may directly alter p53 genes during tumorigenesis.

PMID- 8142015
TI  - Expression in lung tumors and genetic mapping of the novel murine protein kinase
      C eta.
AB  - Protein kinase C eta (nPKC eta) is a member of the protein kinase C family with a
      unique tissue distribution in skin and lung. We analyzed nPKC eta expression in
      normal murine lung and in 36 lung tumors induced by urethane in AC3 F1 and F2
      mice. The nPKC eta-related transcript was present at fivefold to tenfold lower
      levels in tumors than in normal lung controls. We mapped two distinct loci for
      nPKC eta on murine chromosome 12, using linkage analysis in an interspecific test
      cross. The results indicate that the mouse Pkcn-rs1 and Pkcn-rs2 loci were about
      30 cM from the centromere and about 2 cM from each other.

PMID- 8142016
TI  - DNA polymerase arrest by adducted trivalent chromium.
AB  - Carcinogenic chromium (Cr6+) enters cells via the sulfate transport system and
      undergoes intracellular reduction to trivalent chromium, which strongly adducts
      to DNA. In this study, the effect of adducted trivalent chromium on in vitro DNA
      synthesis was analyzed with a polymerase-arrest assay in which prematurely
      terminated replication products were separated on a DNA sequencing gel. A
      synthetic DNA replication template was treated with increasing concentrations of
      chromium(III) chloride. The two lowest chromium doses used resulted in
      biologically relevant adduct levels (6 and 21 adducts per 1,000 DNA nucleotides)
      comparable with those measured in nuclear matrix DNA from cells treated with a
      50% cytotoxic dose of sodium chromate in vivo. In vitro replication of the
      chromium-treated template DNA using the Sequenase version 2.0 T7 DNA polymerase
      (United States Biochemical Corp., Cleveland, OH) resulted in dose-dependent
      polymerase arrest beginning at the lowest adduct levels analyzed. The pattern of
      polymerase arrest remained consistent as chromium adduct levels increased, with
      the most intense arrest sites occurring 1 base upstream of guanine residues on
      the template strand. Replication by the DNA polymerase I large (Klenow) fragment
      as well as by unmodified T7 DNA polymerase also resulted in similar chromium
      induced polymerase arrest. Interstrand cross-linking between complementary
      strands was detected in template DNA containing 62, 111, and 223 chromium adducts
      per 1,000 DNA nucleotides but not in template containing 6 or 21 adducts per
      1,000 DNA nucleotides, in which arrest nevertheless did occur. Low-level, dose
      dependent interstrand cross-linking between primer and template DNA, however, was
      detectable even at the lowest chromium dose analyzed. Since only 9% of chromium
      adducts resulted in polymerase arrest in this system, we hypothesized that arrest
      occurred when the enzyme encountered chromium-mediated interstrand DNA-DNA cross
      links between either the template and a separate DNA molecule or the template and
      its complementary strand in the same molecule. These results suggest that the
      obstruction of DNA replication by chromium-mediated DNA-DNA cross-links is a
      potential mechanism of chromium-induced genotoxicity in vivo.

PMID- 8142017
TI  - Assignment of two human epidermal squamous cell carcinomas cell lines to more
      than one complementation group for the immortal phenotype.
AB  - Two human cell lines derived from squamous cell carcinomas (SCCs) of the
      epidermis, SCC-12 clone F and SCC-13 clone Y, were made to be independent of the
      Swiss 3T3 feeder layer to perform somatic-cell genetic experiments. We fused
      these SCC lines with normal human fibroblasts, and all resulting hybrids senesced
      after completing 12-17 population doublings, suggesting that in part,
      immortalization of the keratinocyte during SCC development results from the loss
      of gene function. We also tested whether these two SCC lines mapped to known
      complementation groups for immortality by fusing them with representatives of
      groups A (GM847), B (HeLa), and C (143B), but most of these hybrids were
      indistinguishable from those derived from homotypic crosses set up as immortal
      hybrid controls. As reported by others, fusions of cell lines from different
      complementation groups-143B (group C) x HeLa (group B) or GM847 (group A) x Hela
      (group B)--resulted in predominantly senescent hybrids. Our results confirmed and
      extended previous observations by others that the phenomenon of senescence is
      dominant to that of immortality, but they did not allow us to assign either of
      the SCC lines we studied to a complementation group for immortality.

PMID- 8142018
TI  - Recovery from ultraviolet-induced growth arrest of primary rat hepatocytes by p53
      antisense oligonucleotide treatment.
AB  - Recent evidence suggests that wild-type p53 prevents cell-cycle progression after
      DNA damage, which may provide a sufficient period for the cells to repair the
      genetic lesions that may otherwise lead to cell death or cellular transformation.
      We tested whether this hypothesis is generally applicable to parenchymal cells of
      internal organs. When primary neonatal rat hepatocytes were exposed to a
      nonlethal dose of ultraviolet light, actinomycin D, or mitomycin C, most cells
      expressed abundant p53 with an abnormally extended half life in their nuclei, and
      their growth was arrested despite treatment with growth factors (epidermal growth
      factor and insulin). When DNA-damaged cells were treated with p53-antisense
      oligonucleotides, p53 expression was significantly suppressed, and an appreciable
      fraction of the cells entered S phase. However, when damaged cells were
      administered p53-sense or retinoblastoma susceptibility gene-antisense
      oligonucleotides, there was no recovery from growth arrest. The data strongly
      suggest that p53 is a component of at least one signal transduction pathway
      leading to growth arrest in DNA-damaged cells.

PMID- 8142019
TI  - Infrequent p53 mutations in 7,12-dimethylbenz[a]anthracene-induced mammary tumors
      in BALB/c and p53 hemizygous mice.
AB  - We conducted experiments to determine if p53 alterations, which are frequent in
      human breast cancers, were also common in murine mammary tumors. In 13 mammary
      tumors from 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/c mice were
      immunohistochemically analyzed for overexpression of p53; p53 protein was not
      detectable. Three of the tumors were established as cell lines in vitro. p53
      protein was rarely detected at passage 4 in these lines but was overexpressed by
      passage 8 in two of them. The p53 nucleotide sequence was shown to be wild type
      in one primary mammary tumor and in the two p53-overexpressing cell lines. One
      cell line that overexpressed p53 in vitro was implanted into BALB/c mice. The
      resulting tumors retained the wild-type p53 nucleotide sequence but no longer
      expressed detectable levels of p53 protein, suggesting that the overexpression of
      wild-type p53 was related to in vitro culture conditions. The effect of DMBA on
      mammary-tumor development was also tested in mice rendered hemizygous for p53.
      These mice and wild-type littermate controls had no differences in susceptibility
      to induction of mammary tumors by oral administration of DMBA. Furthermore,
      Southern blot hybridization detected no gross alterations in the wild-type p53
      allele in mammary tumors from the p53-deficient mice. Point mutation of the wild
      type p53 allele was also infrequent in the DMBA-induced mammary tumors from
      hemizygous p53 mice; it occurred in only one of seven tumors. Thus, the p53 gene
      is apparently not a primary target for genetic alterations in DMBA-induced
      mammary tumors. Next, we examined mammary tumors derived from D1 and D2
      transplantable hyperplastic alveolar nodule (HAN) outgrowths, which rapidly form
      tumors containing Ha-ras mutations after DMBA treatment. As ras and p53 mutants
      can cooperate in transformation, we examined whether D1 and D2 HAN outgrowths
      have p53 mutations. Unlike in the DMBA-induced primary mammary tumors, nuclear
      p53 accumulation was observed frequently (10 of 14) in tumors that arose from D1
      and D2 HAN outgrowths. Direct sequencing of the entire coding region of the p53
      cDNA from six D1 and D2 tumors confirmed that the sequence was wild type.
      Although wild-type p53 was retained in both DMBA-induced mammary tumors and
      mammary tumors derived from D1 and D2 preneoplastic outgrowths, wild-type p53
      overexpression was detected only in D1 and D2 tumors. Therefore, D1 and D2 tumors
      appear to arise by a pathway in which p53 expression is altered, whereas DMBA
      induction affects a different pathway that does not require such alteration.

PMID- 8142020
TI  - 5'-flanking region responsible for endosperm-specific expression of rice
      prolamine chimeric gene in transgenic tobacco.
AB  - The 5' upstream region (-680-(+)40) containing the complete signal peptide coding
      sequence of the rice seed storage prolamine gene was amplified in vitro with
      polymerase chain reaction from the genome of Chinese super rice cultivar Zhonghua
      8. Physical map and DNA sequence analysis showed strong homology with the 5'
      flanking region of rice prolamine gene reported by Kim in 1988. No changes in the
      signal peptide coding sequence and a long leader sequence with several small ORFs
      were found. Chimeric gene containing 5'-flanking region of the prolamine gene has
      been transcriptionally fused with the beta-glucuronidase reporter gene. The
      fusion junction was confirmed by both physical map and DNA sequence analysis. The
      resultant chimeric gene was used to transform the tobacco explants by Ti binary
      system of Agrobacterium tumefaciens LBA4404. With dot and Southern blotting
      hybridization, three transgenic tobacco plants with the copies of chimeric GUS
      genes as many as 20 were obtained. Histochemical analysis revealed that the GUS
      activity in the endosperm tissues of tobacco seeds at the developmental stage was
      about 20 DAP. No GUS activity was found in leaves, stems, roots and flowers of
      the transgenic tobacco plants. Therefore, we concluded that the 5'-upstream cis
      elements from -680 to -18 were enough to confer the endosperm-specific and
      temporal expression of rice prolamine gene.

PMID- 8142021
TI  - Molecular mechanism of high energy proton radiation--Raman spectroscopic
      character of microcosmic damage in the space structure of DNA.
AB  - High energy proton is an important type of the space radiation. The paper
      investigates the radiation effect of high energy proton (27.9 MeV) on DNA aqueous
      solution in the field of the molecular mechanism. The following information about
      the microcosmic damage to the space structure of DNA was obtained: (i) breakage
      of a part of interbase hydrogen bonds which maintained double helical structure
      of DNA; (ii) damage on four bases, in which the damage on adenine ring was the
      most serious; (iii) obvious change of deoxyribose; (iv) serious damage on
      backbone phosphate ion (PO2-) and phosphate diester (PO2) and the occurrence of
      scissions of double-stranded and single-stranded DNAs; (v) obvious decrease in
      the amount of B-form conformation.

PMID- 8142022
TI  - Long-term expression of human factor IX cDNA in rabbits.
AB  - In this study, rabbits were used as a model for gene therapy for hemophilia B.
      Human factor IX cDNA was transferred to cultured normal rabbit skin fibroblasts
      (RSF) by a recombinant plasmid (pCMVIX) or retrovirus (XL-IX or N2CMVIX)
      constructed in our laboratory. Infected fibroblasts capable of synthesizing and
      secreting high levels of biologically active human factor IX protein were
      selected and embedded in a collagen matrix. The latter was surgically implanted
      into rabbits as autografts or allografts. Human factor IX protein was detected in
      the plasma of all the grafted rabbits, and its expression has been maintained for
      more than 10 months at the time of writing. In addition, we have improved and
      simplified the method of implantation from surgically grafting the tissue-like
      matrix to the injection of the infected cell-collagen mixture subcutaneously.
      Using the latter method, human factor IX in rabbits injected with RSF-N2CMVIX
      reached a peak of 480 ng/ml plasma, and its expression has continued for more
      than 3 months at the time of writing. We suggest that the simplified method of
      transplantation by subcutaneous injection would offer an effective and acceptable
      approach to somatic cell gene therapy and may be practical for human trials.

PMID- 8142023
TI  - Stage I clinical trial of gene therapy for hemophilia B.
AB  - This paper describes the first human gene therapy trial for hemophilia B.
      Retroviruses were used to introduce human factor IX into autologous, primary
      human skin fibroblasts from the patients. Recombinant retroviral vector
      containing human FIX cDNA driven by viral LTR promoter (XL-IX) and double-copy
      retroviral vector driven by human cytomegalovirus enhancer-promoter (N2CMV-IX)
      were constructed. After the safety assessment, including soft-agar test, cell
      morphology observation, analysis of endotoxin, chromosome karyotype, allergic
      reaction test, nude mice test, routine pathological test, electromicroscopic
      analysis, and virus detection by PCR, etc., the engineered cells were pooled and
      embedded in collagen mixture, autologously injected into the patients
      respectively. The concentration of human FIX protein of Patient 1 increased from
      71 ng/ml to 220 ng/ml, with a maximum level of 245 ng/ml. The expression of FIX
      has lasted for 6 months at the time of writing. The clotting activity also
      increased from 2.9% to 6.3%, his clinical symptoms have been alleviated
      obviously. The secretion rate of FIX for Patient 2 increased from 130 to 250
      ng/ml, maintained at the level of 220 ng/ml for 5.5 months at the time of
      writing, but the clotting activity has not been increased steadily. There is no
      deleterious effect to be found in the two patients since the ex-vivo cells were
      implanted. The two patients are now under follow-up investigation. We suggested
      that retrovirus-mediated transfer of genes into skin fibroblasts, to be embedded
      in collagen and subcutaneously injected into patients, is a simple and effective
      approach for the gene therapy for hemophilia B.

PMID- 8142024
TI  - Expression of Shiga toxin B subunit at cell surface in E. coli K-12.
AB  - The three parts (Stx17B, Stx27B and StxB) of Shiga toxin B subunit have been
      fused into a cell surface exposed loop of the LamB protein at a BamH I site
      between residues 153 and 154. Western blotting revealed that the three parts of
      Shiga toxin B subunit could be expressed as the LamB fusion proteins in E. coli.
      Indirect immunofluorescence and immunoelectron microscopy analyses showed fusion
      proteins LamB/Stx17B and LamB/Stx27B could be expressed at cell surface in E.
      coli, but fusion protein LamB/StxB could not be expressed at cell surface; it was
      aggregated in cytoplasm and was toxic to host. This expression system provided a
      new way to construct an oral live vaccine against Shigella dysenteriae 1.

PMID- 8142025
TI  - Cloning, sequencing and expression in E. coli of interferon-omega 1 gene.
AB  - Human interferon omega 1 (huIFN-omega 1) gene was isolated and cloned from
      chromosome DNA derived from a Chinese fetal liver via polymerase chain reaction
      (PCR). By determining its nucleotide sequence we proved that the 88th codon
      should be GGA, coding for Gly. After engineering the original IFN-omega 1 gene
      clone to a form that may be expressed as a nonfused protein, we also took the IFN
      omega 1 gene under the control of the PRPL promoter with an expression vector
      pBV220 in E. coli. The antivirus activity of the recombinant IFN-omega 1 is about
      6.5 x 10(7) units/L CULTURE (OD600 = 0.75). Since IFN-omega 1 not only has
      antivirus activity but also shows considerably high homology with animal
      trophoblast proteins which have been proved antiluteolysins as a maternal
      recognition signal for pregnancy, we believe that study on it will be practically
      and theoretically significant.

PMID- 8142026
TI  - Is cAMP decrease essential for resumption of meiosis in mouse oocytes?
AB  - Resumption of meiosis was inhibited in mouse oocyte cumulus complexes (OCC) co
      cultured with pig membrane granulosa (PMG). After 3 and 6 h of co-culture these
      oocytes possessed an intact nuclear envelope and their nucleolar surface was
      associated with granules approximately 80 nm in diameter. Preincubation of OCCs
      for 30, 45, 60 or 90 min followed by co-culture with PMG for 2 h of either OCCs
      or denuded oocytes resulted in germinal vesicle breakdown (GVBD) in approximately
      0, 30, 70 and 100% mouse OCCs and in approximately 30, 60, 80 and 100% denuded
      oocytes, respectively. It seems that the inhibitory contact between mouse oocytes
      and PMG was established during the first h of co-culture. After isolation from
      antral follicles the oocytes contained 2.75 fmol cyclic adenosine 3', 5'
      monophosphate (cAMP). When OCCs were co-cultured for 1, 2 or 3 h with PMG, the
      amount of cAMP per oocyte was 1.34, 1.33 and 1.51 fmol, respectively. After
      culture of OCCs in control medium the amount of cAMP was 1.21, 1.39 and 2.16
      fmol, respectively. The present results suggest that the inhibitory activity of
      PMG is not species-specific. Moreover, PMG prevented resumption of meiosis in
      mouse oocytes in spite of the cAMP drop in oocyte cytoplasm characteristic of the
      resumption of meiosis.

PMID- 8142027
TI  - Treatment of human spermatozoa with follicular fluid can influence lipid content
      and motility during in vitro capacitation.
AB  - In order to evaluate the role of human follicular fluid (HFF) on the fertilizing
      capacity of spermatozoa, we studied the effect of HFF on the lipid composition
      and on the movement characteristics of human spermatozoa. Spermatozoa (spz) from
      normospermic patients were prepared with a discontinuous Percoll gradient and
      incubated in Menezo B2 medium with or without a supplement of 20% HFF (HFF
      Percoll spz and B2-Percoll spz respectively) for 2 and 24 h. After 2 h HFF
      incubation, percentage progressive motility, straight line velocity (VSL), and
      amplitude of lateral head displacement (ALH) were improved in HFF-Percoll spz as
      compared to B2-Percoll spz (P < or = 0.05). After a longer incubation period (24
      h), lipid changes appeared in HFF-Percoll spz with lower levels of cholesterol (P
      = 0.02) and phospholipids (P = 0.05). No modification of the
      cholesterol/phospholipid ratio after 2 and 24 h of incubation in either B2
      Percoll spz or HFF-Percoll spz was observed. Such decreases in lipid content of
      HFF-Percoll spz may be factors which could be taken into account as constituting
      part of membrane modifications during the capacitation process.

PMID- 8142028
TI  - Pronucleus formation in bovine oocytes activated by a single electric pulse.
AB  - Bovine oocytes matured in vitro were stimulated by a single pulse of direct
      current (DC), then cultured for 0.5-6 h and evaluated by light (LM) and
      transmission electron microscopy (TEM). At the light microscopic level, the
      beginning of oocyte chromatin decondensation was first observed 3 h post
      activation (14%). A well-developed pronucleus with evenly granulated nucleoplasm
      surrounded by nuclear membrane was found in 12, 61 and 81% oocytes at 4, 5 and 6
      h post-activation, respectively. The TEM evaluation revealed that nuclear
      membrane vesicules were first visible at 0.5 h post-activation and became even
      more prominent at 1 h. Based on these observations, it is concluded that a
      nuclear membrane starts to form immediately after oocyte activation, while a well
      developed pronucleus appears at 4-6 h.

PMID- 8142029
TI  - Immunoelectron microscopic localization of small nuclear ribonucleoproteins and
      interchromatin granules in the 2-cell mouse embryo.
AB  - The distribution of U1, U2, U4, U5 and U6 small nuclear ribonucleoproteins
      (snRNPs) and interchromatin granules (IGs) was studied by electron-microscopic
      immunocytochemistry (EMI) in early 2-cell mouse embryos at the onset of embryonal
      transcription. The localization of these antigen structures was evaluated with
      respect to nucleoplasmic ribonucleoprotein (RPN) regions consisting of
      interchromatin and perichromatin areas. SnRNP structures of maternal origin
      (labelled with anti-Sm antibody) were widely distributed throughout the
      nucleoplasm. Specifically labelled IGs were detected by gold particle clusters
      distributed in the interchromatin regions of the nucleoplasm. Both
      immunodetections were negative in nucleolar precursor bodies (NPBs). In addition,
      the labelling of condensed chromatin blocks with anti-DNA antibody showed
      heterochromatin topology at this developmental stage. Small condensed chromatin
      blocks were distributed throughout the nucleus and also appeared in association
      with the NPB rim. The observed status quo represents a transient state of nuclear
      structure rearrangement.

PMID- 8142030
TI  - In vitro culture of embryonic disc cells from porcine blastocysts.
AB  - The aim of the present study was to define the conditions of preparation and in
      vitro culture of embryonic discs allowing proliferation of ES-like cells. G5-6
      porcine blastocysts (G0 = day of AI) were cultured in toto; in G10-11
      blastocysts, trophectoderm and primitive endoderm were microsurgically removed
      from embryonic discs (ED) which were cultured either on plastic or on a feeder
      layer. Feeder cells were foetal G30 porcine fibroblasts which had been previously
      irradiated. Culture medium was DMEM supplemented with 0.1 mM beta
      mercaptoethanol, 5% foetal calf serum, 5% Ultroser G and 10(3) IU LIF; cultures
      were performed at 38 degrees C. Colonies were reseeded weekly. Few embryonic
      discs from G5-6 and no elongating blastocysts gave rise to ES-like cells. At
      least 50% G10-11 ED attached and developed multilayered colonies (100 cells) of
      small ovoid ES-like cells. Colonies from 4 sows were maintained in culture for at
      least 8 wk. Addition of PDGF, insulin or both, induced a transitory stimulation
      of growth in G6 or G10-11 ED; TGF beta did not modify growth of G6 ICM. Uterine
      G10-11 flushing medium or retinol induced differentiation of ES-like cells. These
      cells introduced in nude mice induced teratoma.

PMID- 8142031
TI  - Self-selection of lysine by growing pigs: choice combinations between deficient
      or suboptimal and adequate or superoptimal dietary levels according to sex.
AB  - Self-selection of dietary lysine was studied in one 42-d experiment involving 100
      Large White growing pigs, with an equal number of females and castrated males,
      initially weighing 17.7 kg, within 5 treatments of 20 animals in each. A common
      basal diet (17% CP, 13.8 MJ DE/kg) based on maize, soybean meal and peanut meal,
      and containing a deficient level of lysine (0.61%), was used. Supplementary L
      lysine was provided to obtain suboptimal (0.74%), optimal (0.85%) and
      superoptimal (1.21%) levels of total lysine for growth, as assumed from usual
      recommendations. In addition to treatment 1, a control where pigs were fed ad
      libitum a single diet with 0.85% lysine, 4 treatments with free choice of lysine
      within paired diets were compared. These included deficient or suboptimal levels
      of lysine on the one hand and optimal or superoptimal levels on the other
      according to a 2 x 2 factorial plan: 0.61 vs 0.85% (treatment 2), 0.74 vs 0.85%
      (treatment 3), 0.61 vs 1.21% (treatment 4), 0.74 vs 1.21% (treatment 5). The
      results showed sex difference in diet selection according to lysine content.
      Females had a distinct preference for the superoptimal level (1.21%) compared to
      the optimal level (0.85%), especially during the initial period of the trial,
      their requirement being higher than the presupposed 0.85% optimal level. For
      castrated males, the preference for lysine was restricted to the lower 0.85%
      level. The ability of females to self-select a greater proportion of the high
      lysine feed as opposed to castrated males was related to a higher potential for
      lean tissue growth. These results confirm that the growing pig is able to
      differentiate between diets differing only in their lysine contents.
      Complementary observations on plasma-free amino acids suggested the use of diets
      adequately balanced for amino acids when offered for free choice.

PMID- 8142032
TI  - Evaluation of pheasant semen production during the reproductive season.
AB  - The aim of this research was to evaluate the quality and quantity of semen
      production of pheasants during the reproductive season. Fifty-five male pheasants
      (Phasianus colchicus mongolicus) were used from 37-59 weeks of age. Semen samples
      were collected manually on a biweekly basis. At 45 weeks of age, pheasants which
      had never produced (n = 22) or only produced occasionally (n = 7) were discarded
      from the study. The volume of the ejaculate from each male was measured upon each
      semen collection. Sperm concentration and motility were measured for every semen
      collection from the 41st week of age. Body weight was recorded at 38 and 39 weeks
      and then every 2 weeks. The largest percentage (55%) of males producing semen was
      reached at 44 weeks of age. Semen variables showed the following mean values
      during the reproductive season: volume = 105 mg, concentration = 5.86 x 10(9)/ml,
      and motility scale = 2.45 (modest-good). Semen variables were significantly
      influenced by bird and age but not by day of collection.

PMID- 8142033
TI  - [Comparative study of the diaphyseal osseous growth of the tibia between 3 and 12
      weeks in 2 strains of turkey: histological and histomorphometric aspects].
AB  - The comparative cortical growth of the tibiotarsus was studied in 2 turkey
      strains, one light, one heavy, between 3 and 12 weeks of age, using histological
      and histomorphometrical methods. The growth in thickness started earlier and was
      much faster and larger in the heavier turkey strain. The early ovoid shape of the
      cortex of the heavier strain and the difference between the thickness of the
      narrow and the thick cortical faces seemed to be related to the action of strong
      mechanical strains. Nevertheless the diaphyseal cortical ratio remained not
      significantly different in the 2 strains from the age of 3 weeks. The light
      strain exhibited during all the studied periods indicated a more variable mineral
      apposition rate and earlier and more extensive bone remodelling phenomena. Most
      of the growth in thickness parameters were significantly higher in the heavier
      strain when turkeys of the 2 strains were compared at an equivalent weight.

PMID- 8142034
TI  - Effects of a microbial probiotic (Sporolactobacillus P 44) on postprandial porto
      arterial concentration differences of glucose, galactose and amino-nitrogen in
      the growing pig.
AB  - Postprandial kinetics of porto-arterial concentration differences of glucose (G),
      galactose (Gal), L-lactic acid (LA), amino-nitrogen (AN) and urea (U) were
      studied in the pig after the ingestion of 10(7) colony-forming units (cfu) of
      Sporolactobacillus P 44 per g of feed. Eight fistulated pigs (portal vein and
      brachiocephalic trunk; mean body weight 70 +/- 4 kg) were used. The diet was
      based on skimmed milk (32%), barley (30%), maize (10%) and lactose (7%). The
      postprandial blood kinetics, 4 conducted per animal at 1-wk intervals, were
      studied during the 3 h following the ingestion of test meals of 1,000 g basal
      diet (BD) or the same diet supplemented by the bacteria (SD). The apparent
      absorption was estimated from the area between the portal and arterial
      concentrations. The areas of porto-arterial differences of G, Gal and AN of SD
      for the first 3 h after the meal were significantly higher after SD ingestion
      than those measured after BD intake. Plasma concentrations of U and porto
      arterial differences of U and LA were not modified by the probiotic. These
      effects disappeared immediately after dietary supplement interruption, suggesting
      that added bacteria presence in the intestinal lumen was fundamental to the
      modifications observed in apparent absorption.

PMID- 8142035
TI  - [Pathogenic effects of Trypanosoma congolense on the testis of Baoule bulls:
      quantitative and morphometric histology].
AB  - The effect of Trypanosoma congolense on testis was studied in 53 trypano
      resistant "Baoule" bulls by quantitative histology and morphometry. The daily
      spermatozoa production per testis of control groups (n = 45) was 382 +/- 334 x
      10(6) (m +/- sd) and the epididymis contained 0.6 +/- 1 x 10(9) spermatozoa in
      the caput, 0.3 +/- 0.3 x 10(9) in the corpus and 1.2 +/- 1.8 x 10(9) in the
      cauda. The infected bulls (n = 8) showed no significant difference (P > 0.05)
      when compared to the control despite their average low value. The morphometric
      analysis during infection revealed a significant (P < 0.05) decrease (32%) of
      total Leydig cell volume per testis, 4.4 +/- 0.9 cm3 for the control (n = 5) and
      3.0 +/- 0.8 cm3 for infected bulls (n = 8). The number of round spermatids per
      Sertoli cell and the daily round spermatid production (DRSP) per testis were also
      significantly reduced in infected bulls when compared to controls (P < 0.05), 5.2
      +/- 0.7 and 2.8 +/- 2 for round spermatid per Sertoli cell and 6.1 +/- 2.0 and
      3.1 +/- 1.9 x 10(8) for DRSP. These observations indicate that Trypanosoma
      congolense infection alters the interstitial tissue and meotic divisions of
      germinal cells leading to low daily round spermatid production per gram of testis
      in "Baoule" bulls.

PMID- 8142036
TI  - Effect of anaerobic fungi on the ruminal proteolysis in gnotobiotic lambs.
AB  - The establishment of a fungal population composed of the main species usually
      found in ruminants in the rumen of gnotobiotic lambs did not significantly alter
      the in sacco digestibility of meat meal and soybean cake. The proteolytic
      activity of the rumen fluid against 14C-casein was not affected by the fungi.
      Therefore, these microorganisms probably do not play an important role in the
      degradation of proteins in the rumen.

PMID- 8142037
TI  - Vitamin E and fat supplementation of sows and the effect on tissue vitamin E
      concentrations in their progeny.
AB  - A study was conducted to evaluate the effects of supplementing the diets of
      gestating and lactating sows with 3 levels of vitamin E (22, 44 or 88 IU/kg) and
      fat (no fat, 5% tallow, or 5% fish oil) on tissue vitamin E concentrations in
      their progeny. Tissue levels of vitamin E were examined at birth, and then at 14
      and 28 d of age in the suckling piglets. Vitamin E concentration in all tissues
      at birth were very low (hip muscle, neck muscle, lung, brain, heart, kidney < 1.0
      microgram/g tissue). Piglet tissue vitamin E levels at birth were influenced by
      the vitamin E status of the maternal diet during gestation. The piglet tissue
      concentration of vitamin E increased 2- to 3-fold by 14 d of age. Tocopherol
      concentrations greater than 3 micrograms/g tissue were found in the liver, lung,
      spleen, heart and kidney. Tissue vitamin E concentrations of piglets from sows
      that had received fish oil were lower (significantly in 5 cases: P < 0.05) than
      piglets from sows receiving tallow or no fat. Tocopherol concentrations in
      tissues, with the exception of the spleen, increased significantly (P < 0.05)
      with increased vitamin E in the sows' diet.

PMID- 8142038
TI  - [The bovine zona pellucida: differences in macromolecular composition between
      oocytes, pre-treated with A-23187 or not, and embryos].
AB  - The SDS-PAGE method was used to determine the composition of isolated bovine zona
      pellucida (ZP). This egg extracellular coat appears to be characterized by 3
      major glycoproteins (ZP1, ZP2, ZP3), with apparent molecular weight (MW) of 80-70
      kD, 66-63 kD and 60 kD, respectively, as revealed by 1-dimensional SDS-PAGE.
      After 2-dimensional SDS-PAGE, the zona pellucida electrophoretic pattern
      indicates a fourth glycoprotein, thus called ZP4. SDS-PAGE analysis of ZP
      isolated from oocytes and embryos after transit through the genital tract of
      A23187 pretreated oocytes allowed the description of modifications in
      glycoproteinic composition.

PMID- 8142039
TI  - Effect of Eubacterium limosum, a ruminal hydrogenotrophic bacterium, on the
      degradation and fermentation of cellulose by 3 species of rumen anaerobic fungi.
AB  - The degradation and fermentation of cellulose filter paper were studied in axenic
      cultures of 3 species of rumen anaerobic fungi, Neocallimastix frontalis,
      Piromyces communis and Caecomyces communis, and in cocultures containing 1 of
      these fungal strains and Eubacterium limosum, a hydrogenotrophic rumen bacterial
      species. When E limosum was introduced into fungal cultures a slight decrease in
      fungal cellulolytic activity was observed. The end products of the fermentation
      of cellulose found in the cocultures were different from those found in the
      fungal monocultures. E limosum used formate and part of the hydrogen produced by
      the fungi and probably created a shift in the metabolism of the fungi resulting
      in a reduction of lactate and ethanol production.

PMID- 8142040
TI  - Seasonal variation in ovarian and oestrous activity of tropical Menz sheep as
      affected by plane of nutrition.
AB  - Forty-eight mature Ethiopian Menz ewes were used to investigate the effect of
      nutrition on oestrous and ovarian activity in tropical sheep. A control group was
      fed on hay alone and a high nutrition group received an additional 400 g per ewe
      per d of a concentrate feed providing 263 g crude protein/kg dry matter and 10.5
      MJ metabolisable energy/kg dry matter. Half the ewes in each group interacted
      with harnessed vasectomized rams to detect oestrus, which was also verified by
      weekly plasma progesterone assays. Ram presence did not depress feed intake or
      liveweight gain (P > 0.05). The mean percentage of ewes showing oestrus at least
      once a month was very high (95%) and there was a marked reduction in sexual
      activity from June to September, the wet season. Only 79% of ewes cycled in
      August and the number of heats per ewe per month dropped to 1.3 during this wet
      season in contrast to 1.9 the rest of year. Ewes came into oestrus 21 times
      (range 18-23) a year with no significant effect of level of nutrition. Mean cycle
      duration was 17.9 +/- 8.7 d; 22% of cycles were short (< or = 13 d), 56% normal
      (14-19 d), 11% long (20-26 d), 8% silent or missed (27-40 d) and 3% represented
      anoestrus (> or = 40 d) with no major difference due to nutrition level.
      Individual animal progesterone profiles revealed that ewes failing to show
      oestrus had experienced increased silent ovulations. Forty percent of undetected
      heats were from the same animals. We concluded that, although Menz ewes are year
      round breeders, they experience an apparent reduction in sexual activity from
      June to September, which appears to be independent of the level of nutrition, but
      might influence their breeding activity and flock production.

PMID- 8142041
TI  - Experimental modification of vitellogenesis in Japanese quail by trypan blue in
      vivo.
AB  - Ovaries of adult Japanese quails were exposed in vivo to the acid bisazo dye
      trypan blue (TB) which binds to plasma albumin, the plasma precursor of the yolk
      protein alpha-livetin. By a combination of fluorescence microscopy and electron
      microscopy alpha-livetin could be localized in the subdroplets of intermediary
      and yellow yolk spheres. Trypan blue alters vitellogenesis in the non-disc region
      of follicles in rapid growth in a reversible and dose-dependent way. Less yolk is
      produced over 24 h and its morphology is different when compared to controls.
      This yolk is similar to yolk of the germinal disc region where vitellogenesis is
      known to be inhibited physiologically. Several ultrastructural features of the
      germinal disc region are also found in the non-disc region of TB-exposed
      follicles. Our results suggest that the morphology of yellow yolk is linked to
      the rate of deposition. We propose that the inhibitory action of TB on
      vitellogenesis can be explained by a defective receptor-ligand dissociation in
      endosomes.

PMID- 8142042
TI  - Maintenance of sperm production in bucks during a third year of short
      photoperiodic cycles.
AB  - We have previously shown that reproductive seasonality of bucks was prevented for
      2 consecutive years by short photoperiodic cycles. To determine the effect of the
      length of treatment time on bucks subjected to the same photoperiod conditions,
      experiments were continued for a third consecutive year on 3 groups of 6 Alpine
      and Saanen bucks. The control group was kept under natural photoperiodic
      conditions, while the experimental groups were exposed alternately to 1 month of
      long days and 1 month of short days (group 2M) or to 2 months of long days and 2
      months of short days (group, 4M). Prolactin profiles indicated that bucks from
      both experimental groups responded adequately to rapid photoperiod changes as
      their plasma prolactin levels were significantly higher in long days (mean +/-
      SEM; 2M: 61.1 +/- 15.9 ng/ml; 4M: 102.2 +/- 13.5 ng/ml) than in short days (2M:
      35.3 +/- 8.2 ng/ml; 4M: 46.1 +/- 9.0 ng/ml). Testosterone secretion was also
      dependent on day length (P < 0.0001), since testosterone concentrations of
      experimental animals were higher during long days (2M: 7.0 +/- 0.7 ng/ml; 4M:
      10.2 +/- 1.1 ng/ml) than during short days (2M: 4.3 +/- 0.4 ng/ml; 4M: 5.0 +/-
      0.9 ng/ml). Furthermore, controls displayed a high level of sexual behavior
      (always higher than 10%) and the proportion of bucks unable to ejaculate was
      significantly lower (P < 0.01) than the experimental animals (2M: 25.6%; 4M:
      28.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142043
TI  - Psychrotrophs in dairy products: their effects and their control.
AB  - Health concerns and technological effects of psychrotrophic bacteria in dairy
      products are reviewed, as well as methods to control their presence and
      development. The various Gram-negative and Gram-positive psychrotrophic species
      are listed and, with respect to pathogenic psychrotrophs, emphasis is given on
      Listeria monocytogenes, Yersinia enterocolitica, and Bacillus cereus. The
      influence of psychrotrophic bacteria on the quality of raw milk, pasteurized and
      UHT milks, butter, ice cream, cheese, and powders is examined. Public health
      considerations of Listeria monocytogenes, Yersinia enterocolitica, and Bacillus
      cereus of these various dairy products are also presented. Methods that can be
      used to eliminate or control the development of psychrotropic bacteria include
      low or high temperatures, chemicals, gases, the lactoperoxidase system, lactic
      acid bacteria, microfiltration, bactofugation, lactoferrin-related proteins,
      sanitation, flavors, and naturally occurring spore germinants.

PMID- 8142044
TI  - Implications of antinutritional components in soybean foods.
AB  - There are a number of components present in soybeans that exert a negative impact
      on the nutritional quality of the protein. Among those factors that are destroyed
      by heat treatment are the protease inhibitors and lectins. Protease inhibitors
      exert their antinutritional effect by causing pancreatic hypertrophy/hyperplasia,
      which ultimately results in an inhibition of growth. The lectin, by virtue of its
      ability to bind to glycoprotein receptors on the epithelial cells lining the
      intestinal mucosa, inhibits growth by interfering with the absorption of
      nutrients. Of lesser significance are the antinutritional effects produced by
      relatively heat stable factors, such as goitrogens, tannins, phytoestrogens,
      flatus-producing oligosaccharides, phytate, and saponins. Other diverse but ill
      defined factors appear to increase the requirements for vitamins A, B12, D, and
      E. The processing of soybeans under severe alkaline conditions leads to the
      formation of lysinoalanine, which has been shown to damage the kidneys of rats.
      This is not generally true, however, for edible soy protein that has been
      produced under milder alkaline conditions. Also meriting consideration is the
      allergenic response that may sometimes occur in humans, as well as calves and
      piglets, on dietary exposure to soybeans.

PMID- 8142045
TI  - Nisin as a model food preservative.
AB  - Nisin is a ribosomally synthesized peptide that has broad-spectrum antibacterial
      activity, including activity against many bacteria that are food-spoilage
      pathogens. Nisin is produced as a fermentation product of a food-grade bacterium,
      and the safety and efficacy of nisin as a food preservative have resulted in its
      widespread use throughout the world, including the U.S. Nisin is a member of the
      class of antimicrobial substances known as lantibiotics, so called because they
      contain the unusual amino acid lanthionine. Lantibiotics, in general, have
      considerable promise as food preservatives, although only nisin has been
      sufficiently well characterized to be used for this purpose. As the number of
      known natural lantibiotics has increased and their useful characteristics have
      been explored, it has become desirable to synthesize structural analogs of nisin
      and other lantibiotics that do not occur naturally. The fact that lantibiotics
      are gene-encoded peptides synthesized by transcription and translation allows
      structural variants to be generated by mutagenesis. This review focuses on the
      progress that has been made in the construction and biological expression of
      genetically engineered nisin structural analogs. For example, a host-vector pair
      has been engineered that permits the construction of mutants of the structural
      gene for subtilin, which is a naturally occurring structural analog of nisin. The
      vector is designed in such a way that the mutant gene can be substituted for the
      natural subtilin gene in the chromosome of Bacillus subtilis, which in turn
      directs the transcription, translation, posttranslational modifications, and
      secretion of the mature form of the structural analog. Several structural analogs
      have been constructed, and their properties have provided insight into some of
      the structure-function relationships in lantibiotics, as well as their mechanism
      of antimicrobial action. These advances are assessed together with potential
      problems in the future development of nisin analogs as valuable new food
      preservatives.

PMID- 8142046
TI  - Prediction of fetal distress and poor outcome in prolonged pregnancy using
      Doppler ultrasound and fetal heart rate monitoring combined with stress tests
      (II).
AB  - Postterm pregnancies of more than 290 completed gestational days (n = 110) were
      simultaneously supervised after admission by pulsed Doppler ultrasound of the
      common carotid and the umbilical arteries, nonstress and contraction stress tests
      (NST/CST) and vibroacoustic stimulation tests (VAST). The results of these tests
      were blinded for the clinicians. Further decision making was based mainly on
      fetal heart rate (FHR) monitoring. The prognostic value of tests performed < 3
      days before birth predicting fetal distress, low Apgar and pH values in the
      umbilical artery were compared by receiver operator characteristics. Results of
      the NSTs and fetal Doppler measurements of the ratio of resistance indices of
      common carotid/umbilical artery were more predictive of later fetal distress than
      both, VAST and CST (p < 0.01, p > 0.05, respectively). There were no significant
      differences in the prediction of low Apgar values. NST was the only significant
      test for predicting a low pH in the umbilical artery immediately after birth
      compared to the other examinations (p < 0.05). The results suggest that even in
      prolonged pregnancies VAST and CST might be released from routine supervision.

PMID- 8142047
TI  - Fetal blood ferritin and cobalamin in normal pregnancy.
AB  - In a cross-sectional study of 75 singleton pregnancies at 16-38 weeks gestation
      serum cobalamin and ferritin concentrations were measured in fetal and maternal
      blood samples. Fetal serum cobalamin concentration did not change significantly
      with gestation but ferritin concentration increased. The median fetal serum
      concentrations of both ferritin and cobalamin were significantly higher than the
      respective values in the mother. The median fetal-maternal ratio for ferritin was
      3.2 and for cobalamin 1.2. These findings demonstrate that from at least 16 weeks
      gestation, there is efficient iron storage in the fetus and transfer of cobalamin
      from the mother to the fetus against a concentration gradient.

PMID- 8142048
TI  - Technical aspects of transcervical chorionic villus sampling.
AB  - Following the 1990 FDA approval of the Trophocan catheter for use in
      transcervical chorionic villus sampling (CVS), an increasing number of US
      physicians have begun offering the procedure. To obtain privileges to perform
      CVS, some states such as California have enacted legislation requiring the
      performance of a certain number of CVS procedures in pregnancies in which the
      patient has already chosen first-trimester abortion. This practice is not
      universally feasible for legal, logistic, or financial reasons. We describe our
      approach to training in a busy reproductive genetics service. The physician
      initially trains by performing amniocentesis to optimize skills in ultrasound
      directed needle guidance and placement. During this initial period, he or she
      also assists in performing transabdominal CVS procedures. The initial
      transcervical CVS cases should be performed in those situations requiring minimal
      catheter manipulation, or in those individuals undergoing CVS in the setting of
      spontaneous abortion. Cases of increasing difficulty should only be performed as
      skill and familiarity increase. For a physician already skilled and experienced
      in ultrasound-guided invasive procedures, sequential periods of observation at a
      busy center allows him or her to become familiar with the common pitfalls in
      performing transcervical CVS, and thus avoid them. Using this approach, we have
      performed over 5,000 CVS procedures and trained 6 reproductive genetics fellows
      in transcervical CVS.

PMID- 8142049
TI  - Developmental changes of adenocarcinoma-associated antigen.
AB  - The occurrence and serum concentrations of adenocarcinoma-associated antigen
      (ACAA) were studied during the fetal period of life, in newborns and in their
      mothers. The mean concentrations were significantly higher in fetal, newborn and
      maternal sera when compared with the mean concentration of ACAA in healthy,
      nonpregnant adults. Thus, ACAA appears to show fetospecific features as is known
      for other oncofetal proteins. ACAA should be recognized not only as a potential
      tumor marker, but also as a normal protein constituent of human serum.

PMID- 8142050
TI  - Risk estimation of intraamniotic infection development after serial
      amniocentesis.
AB  - Microbial invasion and growth in amniotic fluid play an important role in
      infectious perinatal morbidity and mortality. In order to determine the influence
      of amniocentesis (ACT) on intra-amniotic infection development, we performed a
      study of 239 complete microbiological examinations of amniotic fluid specimens
      obtained by serial interventions. In 1 case (0.42%), during the second procedure,
      Staphylococcus epidermidis was discovered. Neither spontaneous abortion nor
      preterm labor were provoked by the procedure. We can conclude that ACT has been
      confirmed as a safe and successful intrauterine intervention if it is made in a
      proper manner.

PMID- 8142051
TI  - Fetal echogenic bowel on ultrasound: is there clinical significance?
AB  - Though echogenic fetal bowel has been associated with meconium ileus and/or
      peritonitis, it may be a normal finding in the second trimester. The purpose of
      this study is to determine which characteristics might distinguish fetuses
      ultimately having abnormal outcomes in a population at low risk for cystic
      fibrosis. Seven fetuses with echogenic bowel were identified: 5 fetuses < or = 20
      weeks gestation (group 1) and 2 fetuses 20-25 weeks gestation (group 2) at
      diagnosis. Four of 5 group 1 fetuses had resolution of the echogenic bowel during
      the second trimester. One group 2 fetus had a persistent mass associated with
      growth deficiency and trisomy 18. The neonatal bowel evaluation was normal in the
      remaining 2 fetuses although echogenic findings persisted into the third
      trimester. In a low-risk population, echogenic bowel usually resolves without
      neonatal sequelae. Even when persistent into the third trimester, echogenic bowel
      does not uniformly herald an abnormal outcome. Echogenic bowel coexistent with
      other abnormalities (such as growth deficiency or structural malformations) may
      be a comarker for aneuploidy.

PMID- 8142052
TI  - Fetal cardiovascular morphology of interrupted aortic arch type B in rats.
AB  - Interrupted aortic arch type B associated with ventricular septal defect (n = 17)
      or atrioventricular septal defect (n = 2) was induced in 19 of 300 fetuses by
      maternal administration of bis-diamine on the 9th and 10th day of pregnancy.
      After rapid whole-body freezing on the 21st day, the fetuses were studied by
      means of serial cross-sectional photographs of the frozen thorax. In fetuses with
      interrupted aortic arch, the ascending aorta was small, and the ratio of its
      diameter to the diameter of the pulmonary trunk was 0.64 +/- 0.03 (mean +/- SEM)
      in contrast to 0.96 +/- 0.02 in the control. The aortic arch was interrupted
      distal to the left common carotid artery (type B of Cerolia and Patton) in all
      cases.

PMID- 8142053
TI  - In situ morphology of fetal aortic isthmus following ductal constriction in rats.
AB  - To clarify the effect of experimentally increased blood flow to the aortic
      isthmus, in situ cross-sectional morphology of the aortic isthmus and the juxta
      ductal descending aorta was studied in fetal rats. Indomethacin (10 mg/kg) was
      administered to 10 near-term pregnant rats, and fetuses were studied 4 and 24 h
      later with cesarean section, rapid whole-body freezing, sectioning on a freezing
      microtome in a plane perpendicular to the aortic isthmus, and photographing cross
      sections. Fetuses without treatment served as controls. The ductus was
      constricted and its cross-sectional area was 12 +/- 3% (mean +/- SEM, % of
      control; p < 0.05 vs. control) at 4 and 24 h. The aortic isthmus was enlarged and
      the cross-sectional area was 146 +/- 5% at 24 h in response to the increased
      flow. These results support the concept that the size of the fetal aortic isthmus
      can change rapidly depending on the flow in late gestation.

PMID- 8142054
TI  - Antenatally diagnosed seminal vesicular cyst.
AB  - Congenital seminal vesicular cysts represent a rare embryological malformation
      usually associated with ipsilateral renal dysplasia. We report a case which was
      diagnosed antenatally as a ureterocele and found postnatally to be a seminal
      vesicular cyst.

PMID- 8142055
TI  - Impaired fetal blood gas status in polyhydramnios and its relation to raised
      amniotic pressure.
AB  - A substantial proportion of perinatal losses in polyhydramnios occur as
      unexplained normally formed stillbirths. In order to investigate the relationship
      between fetal condition and raised amniotic pressure (AP), fetal blood gas and
      acid-base status were determined together with AP in 22 pregnancies with
      polyhydramnios. At fetal blood sampling, 8 (36%) had a venous pH value and 16
      (73%) a pO2 value below the reference range. Both fetal pH and pO2 were
      significantly negatively correlated with the degree of elevation in AP (y = 7.43 
      0.036x, r = 0.56, p = 0.006, where y = pH and x = AP z score, and y = -1.6 -
      0.48x, r = 0.54, p = 0.01, where y = pO2 z score, respectively). Although some of
      these fetuses were hydropic, had congenital anomalies, or were from multiple
      pregnancies, univariate and multiple logistic regression analyses indicated that
      the above associations could not be accounted for by these potentially
      confounding variables. This work suggests that abnormal fetal blood gas status in
      human pregnancies with poly-hydramnios is associated with elevated AP.

PMID- 8142056
TI  - Recent advances in the management of infections in cancer patients.

PMID- 8142057
TI  - New platinum antitumor complexes.
AB  - Over the past two decades, platinum-based drugs (cisplatin and, latterly, the
      less toxic analogue carboplatin) have conferred significant therapeutic benefit
      to a large number of cancer sufferers. However, there remains scope for
      substantial improvement in the clinical utility of metal coordination complexes
      through the discovery of additional platinum-based complexes (or possibly
      alternative metals). Future drug discovery strategies should focus on tumor
      resistance and its circumvention. To date, only one series of compounds, those
      containing a 1,2-diaminocyclohexane carrier ligand (e.g., oxaliplatin,
      tetraplatin), has entered clinical trial based on their circumvention of acquired
      cisplatin resistance in some (mainly murine) preclinical tumor models. At present
      these agents are in early clinical trial and thus their true clinical utility in
      cisplatin/carboplatin refractory disease is not yet determinable (and may not be
      due to dose-limiting neurotoxicity). Over the past few years, our understanding
      of mechanisms of resistance to cisplatin and its interaction with DNA has vastly
      increased. This new information will undoubtedly guide the development of new
      strategies aimed at the circumvention of intrinsic and acquired tumor resistance
      to cisplatin. Approaches to circumvent resistance will probably involve not only
      the rational development of a new generation of platinum-based drugs (e.g.,
      compounds designed to overcome reduced cisplatin accumulation or enhanced removal
      of cisplatin-induced DNA adducts) but also non-platinum drugs which are capable
      of modulating resistance (e.g., modulators of signal transduction pathways, ras
      and myc oncogene expression and glutathione biosynthesis). One may look forward
      with a great deal of optimism that these promising new approaches will result in
      clinical benefit by the end of the century. Nevertheless, cisplatin and
      carboplatin remain the standard anticancer drugs to which novel platinum-based
      complexes must be compared.

PMID- 8142058
TI  - Benign breast disease and cancer risk.

PMID- 8142059
TI  - The biological evaluation of novel antioestrogens for the treatment of breast
      cancer.

PMID- 8142060
TI  - Role of HIV infection in the hematologic manifestations of HIV seropositive
      subjects.

PMID- 8142061
TI  - Effect of acute ethanol treatment on epidermal growth factor receptor in the rat
      stomach.
AB  - The present study investigated the effect of acute ethanol (ETOH) treatment on
      the epidermal growth factor (EGF) receptor in rat gastric mucosa using two
      different experimental models. In the in vitro experiments, gastric mucosal cells
      were incubated with 0, 0.05, 0.1, 0.25, and 0.5% ethanol in Dulbecco's modified
      Eagle's medium (DMEM) for 30 min and then used for the membrane preparation. The
      EGF receptor binding assay indicated that cells incubated in the presence of
      ethanol displayed a concentration-dependent increase (r = 0.85) in the 125I-EGF
      binding. The Western blot analysis using anti-EGF-receptor antibody revealed that
      ethanol in vitro caused reduction in the immunoreactivity of the major 170-kDa
      protein. There were also alterations in the minor protein bands (140, 120, and 50
      kDa). In the in vivo experiments, rats that fasted overnight were given 1.0 ml of
      saline or ethanol (5, 10, or 15%) by gastric intubation 30 min before sacrifice.
      In comparison with the saline controls, ethanol treatment caused a decrease of
      the EGF receptor binding to the gastric mucosal membrane (saline: 5%: 10%; 15%
      ETOH, 1.46 +/- 0.18: 1.13 +/- 0.17: 1.27 +/- 0.19: 0.84 +/- 0.14, p < 0.02; mean
      +/- SEM, n = 9). Furthermore, the immunoblot analysis revealed concentration
      dependent decrease in the intensity of the major 170-kDa protein with ethanol.
      The reduction in the EGF receptor binding and the impairment of the receptor
      protein might be due to the nonspecific damage of the gastric mucosal membrane by
      ethanol.

PMID- 8142062
TI  - Alcohol consumption mimics the effects of a high-fructose, low-copper diet in
      rats.
AB  - The consumption of a high-fructose diet that is inadequate in copper produces
      numerous pathologies which eventually lead to the mortality of the animals. In
      contrast, the consumption of a high-starch diet that is inadequate in copper does
      not produce abnormalities and the animals survive. Ethanol has been chosen as an
      agent to mimic the fructose effect in copper deficiency. The administration of
      20% ethanol in the drinking water of rats fed a starch-based diet that was
      inadequate in copper resulted in a depressed growth rate, anemia, pancreatic
      atrophy, and heart hypertrophy. All these signs were similar to the signs exerted
      by fructose feeding when it was combined with copper deficiency. Polyol pathway
      in the liver and kidney was affected by both ethanol and fructose consumption.
      Ethanol did not aggravate the signs associated with copper deficiency in rats fed
      fructose, but it exacerbated the signs associated with copper deficiency in rats
      fed starch. Certain metabolic pathways that are unique for fructose and ethanol
      may be responsible for the exacerbation of copper deficiency.

PMID- 8142063
TI  - Hepatic lipid profiles in miniature pigs after alcohol feeding.
AB  - Changes in lipid profiles have not been reported for the known increases in total
      lipid content in livers of alcoholics. We have reported a lowering of the beta
      oxidative capacity of alcoholic livers, and therefore would expect a lower
      turnover of fatty acids in these livers, and thus a change in lipid profile. The
      percentage composition of saturated and unsaturated fatty acids in the liver of
      alcohol-fed miniature pigs versus the controls, as well as the function of
      distance from the main hepatic vein, have both been determined in this study
      involving the feeding of ethanol for one year. Livers of alcohol-fed miniature
      pigs contained more total lipids than those of controls. Results also indicated
      significantly higher percentages of free fatty acids and triglycerides in the
      alcohol-fed miniature pigs, and also an increase in percentage total neutral
      lipids. The effect of distance from the main blood source (and therefore
      oxygenation) gave a fatty acid profile that showed an increase in the ratio of
      saturated to unsaturated fatty acids with increasing distance from the right
      hepatic vein. This change in ratio was independent of alcohol feeding.

PMID- 8142064
TI  - Association of high density lipoprotein with whole blood-associated acetaldehyde
      levels.
AB  - We hypothesized that while moderate drinking is associated with increasing levels
      of high density lipoprotein (HDL) levels, excessive drinking of ethanol might, in
      fact, be associated with lower HDL levels and by implication increased
      cardiovascular risk. We therefore performed analyses of whole blood-associated
      acetaldehyde (WBAA) as a measure of drinking behavior and HDL on blood samples
      from 2780 individuals applying for life insurance. Whole blood-associated
      acetaldehyde correlated positively with HDL in the entire sample set throughout
      the range of values (R = 0.101, p = 0.0001). The relationship held for females (N
      = 477, p = 0.036) but was stronger for males (N = 2277, p = 0.0001). We conclude
      that ethanol consumption correlates positively with HDL for both males and
      females and that the relationship persists through higher ranges of ethanol
      consumption.

PMID- 8142065
TI  - Absence of acute tolerance to ethanol hypnosis in F-344 and BN/BIRIJ rats.
AB  - Male Fischer 344 (F-344) rats of three different ages (4, 13, and 25 months) and
      male Brown Norway (BN/BIRIJ) rats (4 months) were injected (IP) with a hypnotic
      dose of ethanol (3.0 g/kg, 10% w/v in saline). Half of the animals were
      decapitated and brains extracted immediately upon loss of the righting reflex
      (LRR), while the other half were allowed to reach recovery of the righting reflex
      (RRR), at which time brains were extracted. Brain alcohol analyses revealed
      significantly higher concentrations in young F-344 rats at both LRR and RRR,
      indicating less sensitivity of target tissue to ethanol hypnosis in the young of
      that strain. All age groups of the F-344 rats as well as the young BN/BIRIJ rats
      displayed lower brain concentrations of ethanol at RRR than at LRR, a finding
      opposite to that characteristic of acute tolerance. The relationship of LRR to
      RRR values did not differ among the age groups of F-344 rats. We conclude that
      the F-344 and BN/BIRIJ strains do not develop acute tolerance to ethanol
      hypnosis. The findings are consistent with the hypothesis that animals with low
      ethanol preferences, such as the F-344 and BN/BIRIJ strains, also have low
      capabilities to develop acute tolerance to ethanol hypnosis.

PMID- 8142066
TI  - Sex differences in schedule-induced alcohol consumption.
AB  - Six female and five male Wistar rats obtained food by pressing a lever on a fixed
      interval (FI) 60-s schedule in the presence of a sipper tube which allowed access
      to an alcohol solution. Systematic manipulation of the alcohol concentration
      revealed that male rats consumed higher alcohol concentrations (v/v) than female
      rats to obtain maximum alcohol intake (g ETOH/kg) during an experimental session.
      Males also reached higher blood alcohol levels (BALs) than females. Individual
      lick rates varied over a small range when the FI schedule parameter was
      manipulated (20 s and 180 s) during probe sessions. Very few licks were observed
      when all pellets were presented at the beginning of the session, during
      extinction, or during sessions in which only a few pellets were presented.
      Reduction of the solution's alcohol concentration to half the maximum
      concentration or presentation of distilled water resulted in increased lick rates
      at most values of the FI schedule in four of the five male subjects, but not in
      female subjects. Alcohol intake during sessions in which half the maximum alcohol
      concentration was available was lower than that observed during sessions in which
      subjects consumed the maximum alcohol concentration. The lick rate data in
      conjunction with those on alcohol intake suggest that male rats, but not female
      rats, maintained blood alcohol concentrations at levels which they had also
      reached during sessions in which the maximum alcohol concentration was available
      from the sipper tube.

PMID- 8142067
TI  - Hyperactivity in preweanling rats following postnatal alcohol exposure.
AB  - Neonatal alcohol exposure in rats has been used as a model to study the effects
      of third-trimester alcohol consumption in humans. In the present research, male
      and female rat pups were artificially reared (AR) and received condensed alcohol
      exposure (6 g/kg/day or 4 g/kg/day) on postnatal days (PNs) 4 through 9. Controls
      consisted of both artificially reared animals receiving maltose-dextrin
      substituted for alcohol and normally reared animals. These rats were tested for
      open-field activity at 18 days of age for four days. Both male and female rat
      pups that received the high dose of alcohol (6 g/kg/day) evidenced overactivity
      relative to pups in both control groups. These findings extend previous work and
      indicate that neonatal alcohol exposure can induce hyperactivity in young male
      rats.

PMID- 8142068
TI  - Phenotype of lymphocytes mediating copolymer-specific humoral immunity in ethanol
      consuming C57BL/6 mice.
AB  - Little is known about the mechanisms of impaired immune function in alcoholic
      patients. We have previously shown that ethanol consumption by mice alters
      copolymer-specific humoral and cellular immune responses. Does ethanol
      consumption eliminate suppressor T cells, allowing nonresponder mice to make
      humoral immune responses to poly(Glu50Tyr50) (GT)? Female C57BL/6 mice were fed a
      nutritionally complete liquid diet containing 35% ethanol-derived calories for up
      to 33 days. Control mice were fed an isocaloric control liquid diet or remained
      on a solid diet and water. Mice fed the ethanol-containing diet made GT-specific
      plaque-forming cell (PFC) responses, whereas mice fed liquid control or solid
      diets did not. Lymphocytes from ethanol liquid diet-consuming mice helped
      splenocytes from either solid or liquid control mice to make a GT-specific PFC
      response. The cells mediating help were nylon wool nonadherent, CD4-bearing T
      cells. These findings suggest that ethanol does not eliminate copolymer-specific
      suppressor cells, but instead alters the functional capability of helper T cells
      for humoral immune responses.

PMID- 8142069
TI  - Effect of disulfiram administration on rat brain glutathione metabolism.
AB  - Chronic administration of disulfiram (DS) to rats was found to affect glutathione
      (GSH) metabolism. Glutathione was measured in the rat brain following DS
      administration. Reduced glutathione was decreased significantly (1.52 +/- 0.3
      mumol/g; p < 0.001), with a concomitant increase in oxidised glutathione (GSSG)
      content (0.12 +/- 0.013 mumol/g; p < 0.001) in the brain as a consequence of DS
      treatment. However, total glutathione (GSH + GSSG) content of the experimental
      group did not show any appreciable change. Similar changes were observed in the
      liver following chronic DS treatment. Brain glutathione reductase (GR) activity
      was found to be significantly depleted (100 +/- 0.16 mumol/min/mg protein), but
      glutathione peroxidase (GP) activity was not affected in rats chronically treated
      with DS. It is reported that the treatment with DS decreases the GSH content,
      with a concomitant increase in GSSG level, and perturbs the GSH/GSSG redox
      status, inducing an oxidative stress on the brain. Glutathione reductase
      implicated in maintaining GSH/GSSG homeostasis by replenishing GSH is also
      affected by DS potentiating the oxidative damage of the tissue. This effect of DS
      on glutathione metabolism in the brain would explain some of its known neurotoxic
      effects.

PMID- 8142070
TI  - Infrequent cellular coexistence of NADPH-diaphorase and calretinin in the
      neurosecretory nuclei and adjacent areas of the rat hypothalamus.
AB  - Colocalization of the calcium-binding protein calretinin and NADPH-diaphorase
      activity at the cellular level was studied in the magnocellular secretory nuclei
      of the rat hypothalamus using sequential immunocytochemical and histochemical
      staining of the same sections. A low degree of colocalization of these markers
      was observed in certain cellular subpopulations within all the areas considered
      (supra-optic, paraventricular, circular and both fornicals nuclei and in the
      hypothalamic area located between the supraoptic and paraventricular nuclei).
      However, since in the paraventricular nucleus both markers were expressed by
      different neuronal populations, the coexistence was almost non-existent in some
      subdivisions of this nucleus. This rare coexistence strongly suggests that NADPH
      diaphorase and calretinin are related to different functions shared by restricted
      hypothalamic neuronal populations.

PMID- 8142071
TI  - Calcitonin gene-related peptide-like immunoreactivity in spinal cord and superior
      cervical ganglion of the Djungarian hamster (Phodopus sungorus).
AB  - The indirect immunofluorescent method was employed to investigate the
      distribution of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI)
      in the spinal cord and superior cervical ganglion of the Djungarian hamster
      Phodopus sungorus. In cross-sections of the spinal cord, immunoreactive fibres
      and terminals were found in laminae 1 and 2 in high density, in the dorsolateral
      (Lissauer's) tract, in ventral and lateral horns, and in the area surrounding the
      central canal. A few CGRP-LI perikarya were seen in the ventral but not the
      dorsal horn. CGRP-LI was further observed in preganglionic sympathetic neurons
      which were labelled by retrograde axonal transport of fluoro-gold (FG) following
      injection of the substance unilaterally into the superior cervical ganglion.
      Preganglionic sympathetic neurons (PSN) were localized ipsilateral to the
      injection site mainly in the intermediolateral nucleus and the lateral funiculus
      of the upper thoracic segments. Most PSN exhibited CGRP-LI. Immunoreactive PSN
      were not seen contralaterally to the site of FG application nor in animals that
      did not receive injections. When the preganglionic fibres were ligated 4 days
      before perfusion, CGRP-LI cell bodies were found in preganglionic sympathetic
      neurons similar to the situation seen upon FG treatment. In the superior cervical
      ganglia of untreated hamsters, immunoreactive fibres were seen to enter the
      ganglion in which they terminated at non-immunoreactive principal ganglion cells.
      The present study, the first in a hamster species, describes the widespread
      distribution of CGRP in the spinal cord of P. sungorus and supports the view that
      considerable interspecies differences exist in occurrence and location of this
      neuropeptide.

PMID- 8142072
TI  - Delta opioid receptor mRNA distribution in the brain: comparison to delta
      receptor binding and proenkephalin mRNA.
AB  - The recent cloning of the mouse delta opioid receptor (Evans et al., 1992;
      Kieffer et al., 1992) has demonstrated it to be a member of the seven
      transmembrane G-protein coupled family of neurotransmitter receptors. The present
      study describes the cellular localization in the central nervous system (CNS) of
      an mRNA encoding this receptor and compares it with the distribution of delta
      receptor binding and proenkephalin mRNA using a combination of in situ
      hybridization and receptor autoradiographic techniques. Delta receptor mRNA was
      visualized with a cRNA probe (472-903 bp) corresponding to transmembrane domains
      III-VI of the receptor, while proenkephalin mRNA was labeled with a cRNA probe to
      exon 3 (139-832 bp). A high level of correspondence was observed between the
      distribution of delta receptor mRNA and delta receptor binding as defined by the
      selective ligand [3H]D-Pen2-Pen5-enkephalin. Delta receptor mRNA and binding were
      expressed in the neocortex, caudate-putamen, nucleus accumbens, olfactory
      tubercle, diagonal band of Broca, amygdala and the nucleus of the solitary tract.
      Discrepancies in the distribution of delta receptor mRNA and binding in the
      olfactory bulb, hippocampus, globus pallidus and substantia nigra pars
      reticulata, may in part be due to differential receptor synthesis and transport.
      These results are discussed in relation to the distribution of proenkephalin mRNA
      and how this may affect our understanding of opioid circuitry in the CNS.

PMID- 8142073
TI  - The distribution of dopamine D2 receptor heteronuclear RNA (hnRNA) in the rat
      brain.
AB  - Conventional in situ hybridization methods have been useful in characterizing the
      anatomical distribution of cells in the central nervous system that express
      dopamine D2 receptor mRNA. However, due to the large size of the D2 mRNA pool,
      this method may be insensitive to changes in D2 gene transcription. We have
      developed a method of hybridizing a 35S-labelled cRNA probe to an intron in the
      D2 receptor gene in order to measure the amount of primary transcript or
      heteronuclear RNA (hnRNA) in D2-expressing cells. Introns are found uniquely in
      hnRNA and are thought to be short-lived intermediates. Thus, monitoring introns
      could represent a more direct measure of D2 gene transcription. The anatomical
      distribution of the D2 hnRNA is similar to the distribution of D2 mRNA in the rat
      brain. D2 heteronuclear RNA was found in the nuclei of cells in the caudate
      putamen, nucleus accumbens, hippocampus, olfactory tubercle, substantia nigra,
      ventral tegmental area, and zona incerta. Other regions that contain D2 mRNA, but
      do not demonstrate intronic signal, include the globus pallidus, prefrontal,
      cingulate, entorhinal, and piriform cortex, septum, and amygdala. However, these
      areas have low amounts of D2 mRNA and may contain levels of D2 hnRNA that are
      below detection. Heteronuclear RNA quantitation by solution hybridization
      followed by RNase protection was performed on striatum, substantia nigra,
      cerebral cortex, hippocampus, hypothalamus, and pituitary using a D2 intron
      7/exon 8 border probe. These results corroborate the distribution of hnRNA
      revealed with intronic in situ hybridization. In addition, protection assays were
      able to detect hnRNA in areas that express low levels of D2 like the cortex,
      hippocampus and hypothalamus. hnRNA/mRNA ratios calculated from intron/exon
      border probe protection assays were not equivalent for all the tissue areas
      studied, indicating that transcription and/or hnRNA half lives may differ between
      tissues that express D2 receptors. The combined use of intronic in situ
      hybridization and intron/exon border protection assay as an index of D2 gene
      transcription and RNA processing provides more information than measuring the
      mRNA pool alone. It may also prove to be a more useful measure of gene
      regulation, allowing for evaluation of gene responses to acute treatments.

PMID- 8142074
TI  - Intravenous administration of interleukin-1 beta induces Fos-like
      immunoreactivity in corticotropin-releasing hormone neurons in the
      paraventricular hypothalamic nucleus of the rat.
AB  - It has been shown that acute administration of recombinant human interleukin 1
      beta (IL-1) to rats elicits an activation of the pituitary-adrenal axis. In the
      present study we investigated immunohistochemically the expression of Fos-like
      immunoreactivity (Fos-LI) in the hypothalamus of rats following intravenous
      injection of IL-1. One, 2 and 4 h after IL-1 or physiological saline injections,
      rats were killed and perfused, and the brains processed for Fos
      immunohistochemistry. Dense populations of neurons containing Fos-LI-positive
      nuclei were found in the paraventricular hypothalamic nuclei (PVH) of IL-1
      treated rats. In particular, the dorsal medial parvocellular part, but also some
      of the other parvocellular subdivisions contained many Fos-LI neurons. Maximal
      induction of staining was found at a dose of 5 micrograms/rat after 1 or 2 h
      survival, while immunostaining had decreased to almost control levels after 4 h.
      No Fos-LI was found in the PVH of control animals. Double immunocytochemical
      staining for Fos and corticotropin-releasing hormone (CRH) revealed that Fos-LI
      was predominantly present in parvocellular CRH-containing neurons of the PVH. The
      finding that peripherally injected IL-1 induces Fos-LI in hypothalamic CRH
      neurons strengthens the hypothesis that these neurons are part of the circuitry
      mediating IL-1-induced activation of the pituitary-adrenal axis.

PMID- 8142075
TI  - Parvalbumin and calbindin in the rat claustrum: an immunocytochemical study
      combined with retrograde tracing frontoparietal cortex.
AB  - The distribution of the calcium binding proteins parvalbumin and calbindin D-28k
      was examined in the claustrum of the rat by means of immunohistochemistry. The
      two proteins displayed a different and largely complementary pattern of
      distribution. Parvalbumin-immunostaining was intense in the neuropil of the
      dorsal claustrum and virtually absent in the neuropil of the ventral claustrum;
      parvalbumin-immunoreactive neuronal cell bodies were relatively numerous in the
      dorsal claustrum and were detected only occasionally in the ventral region. On
      the other hand, calbindin-immunostaining was prevalent in the ventral claustrum;
      very few calbindin-positive neurons were seen in the dorsal sector of the
      nucleus, whereas they were relatively more numerous in the ventral claustrum. The
      cell bodies of the majority of the claustral parvalbumin- or calbindin
      immunoreactive neurons were oval or round, but immunostained polymorphous neurons
      were also observed. The surface of the immunopositive dendritic branches was
      smooth, with no evidence of spines. Fluorescent retrograde tracing was combined
      with immunohistofluorescence to determine whether the parvalbumin-containing
      claustral cells project to the frontoparietal cortex. Neurons labelled after
      large fluorogold injections in frontoparietal cortical fields were highly
      intermingled in the dorsal claustrum with parvalbumin-immunoreactive cells but
      the two neuronal populations were separate. These data show that parvalbumin
      immunoreactive claustral neurons do not project to the frontoparietal cortex. In
      addition, although these cells may project to other cortical or subcortical
      targets, the present findings suggest that they may represent, at least in part,
      local circuit claustral neurons, corresponding to the aspiny intrinsic neurons
      described in the rat claustrum in studies based on Golgi impregnation.

PMID- 8142076
TI  - Postnatal calcitonin gene-related peptide in the superior olivary complex.
AB  - The purpose of this study was to investigate quantitatively the distribution of
      calcitonin gene-related peptide (CGRP)-positive neurons within the superior
      olivary complex (SOC) at various postnatal ages. In the lateral superior olive
      (LSO), most if not all, CGRP-positive cells correspond to the cholinergic portion
      of the lateral olivocochlear system which innervates the cochlea. Brains from 1
      day old (P1) through juvenile (P30) hamsters were used. At all ages, CGRP
      positive neurons were seen throughout the various nuclei of the SOC. There was a
      dramatic shift in the distribution of CGRP-positive neurons from being
      predominantly periolivary to being predominantly confined within the LSO. The
      number of CGRP-positive neurons clearly increased as a function of increasing
      age. At the earliest postnatal ages, the LSO contained few if any immunostained
      cells, whereas at later ages the LSO contained the majority (greater than 70%) of
      the immunostained cells. Assuming that these CGRP-positive cells within the LSO
      correspond to olivocochlear neurons, these data suggest that in hamsters the
      lateral olivocochlear system may be immature at birth up until the second
      postnatal week.

PMID- 8142077
TI  - Through the eyes of the pediatric oncology nurse.

PMID- 8142078
TI  - A comparison of three theories of nursing used as a guide for the nursing care of
      an 8-year-old child with leukemia.
AB  - This article evaluates three nursing theories that can be used to provide a
      framework for holistic pediatric oncology nursing practice: the Roy Adaptation
      Model, the Neuman Systems Model, and the Orem General Theory of Nursing. Each
      theory is compared in terms of its view of man, health, environment, nursing, and
      the nursing process. Critique of each theory is presented. The decision of which
      theorist to use as a basis for practice is left to the individual nurse. This
      article explicates the similarities and differences in the three theories.

PMID- 8142079
TI  - The Journal of Pediatric Oncology Nursing has become an essential resource.

PMID- 8142080
TI  - When I began as production editor for the Journal of Pediatric Oncology Nursing.

PMID- 8142081
TI  - The 1992 APON Delphi study to establish research priorities for pediatric
      oncology nursing. Association of Pediatric Oncology Nurses.
AB  - The Association of Pediatric Oncology Nurses (APON) recently sponsored a two-wave
      Delphi study to identify the most important research priorities for pediatric
      oncology nursing. Seventy-five research priorities were rated for importance by
      227 APON members. The majority of these members were inpatient or ambulatory care
      nurses who had been in pediatric oncology more than 25 months. The top 10
      research priorities were primarily about nursing procedures and psychosocial care
      needs of patients and families. The top priority was to "measure the quality of
      life and late effects of treatment in long-term survivors of childhood cancer."
      Study findings will be used to encourage researchers to conduct research on these
      priorities and to encourage funding organizations to support research related to
      these priorities.

PMID- 8142082
TI  - Parental refusal of treatment.

PMID- 8142083
TI  - Experimental research--level III.

PMID- 8142084
TI  - EMLA.

PMID- 8142085
TI  - [Reliability of forensic evidence in breath alcohol analysis].
AB  - Drinking experiments were performed by using a device-combination appreciated by
      the German National Institut of Health (BGA) as being evidential and proposed as
      prototype for the future practice of breath-alcohol analysis. Comparing the
      breath- (BrAC) and blood alcohol-concentrations (BAC), however, there were
      relevant deviations. Our evaluation of the facts published Schoknecht
      demonstrated nevertheless distinct divergences in comparison to the blood alcohol
      determination: A BAC-nominal of 1% gave divergences of the nominal up to 0.25%
      resulted from the measured BrAC-values of Schoknecht on corresponding conversion.
      The divergences are distinctly above those that are tolerated by legislation
      according to previous standards for the blood alcohol determination. Consequently
      it requires further checking in standardized experiments and field experiments in
      order to be able to judge the practice usefulness; furthermore such further
      checking would have to be implemented by unconcerned institutions. Basing on
      these experiments an evidential breath-alcohol analysis for forensic purposes has
      not been established yet.

PMID- 8142086
TI  - The postmortem blood alcohol concentration and the water content.
AB  - Determination of blood alcohol concentration and water content were performed on
      blood specimens from 71 bodies. Two blood specimens were sampled from each body.
      First-specimens (short-time-specimens) were sampled from 0 to 9.6 hours
      postmortem, in mean 2.1 hours. Second-specimens (long-time-specimens) were
      sampled from 8.0 to 229.9 hours postmortem. The relation between the blood
      alcohol concentration and the blood water content in the two blood specimens
      (first and second) is described by a multiple regression equation. The equation
      gave as result: if the body had no signs of putrefaction, the difference in water
      content between the short-time-specimens and the long-time-specimens has a
      significant influence on the blood alcohol concentration. This was not the case
      if the body had visible signs of putrefaction. Then other factors influence the
      blood alcohol concentration more than the water content. Our study also indicates
      that if a blood alcohol determination is performed on whole blood, and the blood
      specimen was sampled shortly after death from a case of bleeding shock, a
      correction of the blood alcohol concentration should be done if the blood water
      content is higher than 82%.

PMID- 8142087
TI  - Assessment of alcohol dependence and other psychiatric disorders: implications
      for rehabilitation programs of the DUI offender.
AB  - This paper focuses on the psychological make-up or profile of the first time
      "apprehended" Driving Under the Influence offenders from the City of Pittsburgh,
      Pennsylvania. The profiles are compiled using a variety of psychological tests
      assessing issues of: Alcohol Dependence, Major Depression, Personality deviance,
      alcohol induced Organicity and severe Psychiatric impairment (symptoms of
      schizophrenia and manic-depressive disorders). 91% of the alcohol impaired
      drivers complained of at least some acute symptoms of depression. However, in
      total 38% of the sample showed significant signs of a clinical psychiatric
      syndrome (one requiring intervention or treatment) in addition to alcohol
      dependence. The Michigan Alcohol Screening Test and the MacAndrews Alcoholism
      Test proved to be a useful combination in defining alcohol dependence.

PMID- 8142088
TI  - [Contribution of automobile technology to traffic safety].

PMID- 8142089
TI  - Soil ingestion by children and adults reconsidered using the results of recent
      tracer studies.
AB  - Estimates of human exposure to soil are often needed to investigate potential
      risks to public health from toxicants released into the environment. Using the
      results of two recent tracer studies, estimates of average daily soil ingestion
      in young children and over a lifetime were ascertained. After establishing the
      distribution of the recoveries of the tracers in adults, the most reliable
      tracers were identified using an analysis of variance and Tukey's multiple
      comparison procedure. The identified reliable tracers were then employed to
      derive estimates of mean daily soil ingestion in young children. Ingestion rates
      were first adjusted to address the age differences of the children enrolled in
      the studies. A mean daily intake and variance were then determined. Estimates of
      soil ingestion over a lifetime were established based on levels determined in
      children.

PMID- 8142090
TI  - Development and application of risk analysis methods to stationary sources of
      carcinogenic emissions for regulatory purposes by the South Coast Air Quality
      Management District.
AB  - Desirable qualities of a risk assessment procedure for use in routine assessment
      of the impact of new and modified stationary sources of carcinogenic emissions
      are: (1) readily available analysis techniques and (2) simplicity when applied to
      small sources. Regulatory Gaussian models have these qualities but are limited by
      their accuracy at large distances and the difficulty of calculating the cancer
      incidence. Calculation of risk for the maximally exposed individual (MEI risk)
      and cancer incidence is discussed, and the relations found among MEI risk, de
      minimus individual risk, cancer incidence, population density, carcinogenic
      source strength, release conditions, maximum distance to de minimus individual
      risk, release period, and distance to nearest receptor found from application of
      these models to a typical situation are described. Suggestions for setting values
      for maximum allowable MEI risk, maximum allowable cancer incidence and de minimus
      individual risk are also presented. Several types of carcinogenic sources are
      examined for their cancer impact. The effect of various maximum allowable
      exposure parameter values on the source's acceptability is also examined.
      Screening methods for both MEI risk and cancer incidence is discussed.
      Application of the analysis method to numerous sources is presented, including
      use of an empirical equation for cancer incidence.

PMID- 8142091
TI  - Respiratory effects of sevoflurane used in combination with nitrous oxide and
      surgical stimulation.
AB  - STUDY OBJECTIVE: To evaluate the respiratory effects of sevoflurane anesthesia
      with and without nitrous oxide (N2O) during surgical stimulation. DESIGN:
      Randomized study. SETTING: Operating theater at a university hospital. PATIENTS:
      10 patients scheduled for minor head or neck surgery. INTERVENTIONS: Sevoflurane
      anesthesia was administered alone or in combination with N2O. After basal
      measurements were recorded, the following end-tidal anesthetic concentrations
      were administered: Group 1 = 1.3 minimum alveolar concentration (MAC) sevoflurane
      alone; Group 2 = 0.9 MAC sevoflurane with 0.4 MAC N2O; Group 3 = 1.5 MAC
      sevoflurane alone; Group 4 = 1.1 MAC sevoflurane with 0.4 MAC N2O. MEASUREMENTS
      AND MAIN RESULTS: PaCO2, minute volume (VE), respiratory rate, tidal volume (VT),
      percentage of rib cage contribution to tidal volume (%RC), rate of inspiratory
      time in a breath cycle (TI/Ttot, where TI = inspiratory time and Ttot = tidal
      respiratory time), and mean inspired flow (VT/TI) were measured. The substitution
      of 0.4 MAC N2O for sevoflurane decreased PaCO2 and increased VE, with a
      consequent increase in VT. At 1.3 MAC sevoflurane-N2O anesthesia, spontaneous
      respiration maintained PaCO2 at appropriate levels (42.7 +/- 3.6 mmHg). At 1.3
      MAC sevoflurane alone and 1.5 MAC sevoflurane-N2O anesthesia, spontaneous
      respiration was moderately depressed. Sevoflurane and N2O combined did not change
      %RC or TI/Ttot. CONCLUSION: Sevoflurane administered at an appropriate anesthetic
      depth maintained spontaneous respiration at acceptable levels during surgical
      stimulation, especially when combined with N2O.

PMID- 8142092
TI  - Effect of epidural morphine on sedation requirements during regional anesthesia.
AB  - STUDY OBJECTIVE: To examine the effect of using analgesic doses of epidural
      morphine on midazolam requirements for conscious sedation during regional
      anesthesia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING:
      Operating rooms at a university hospital. PATIENTS: 20 ASA physical status II and
      III patients aged 50 to 70 years undergoing elective peripheral vascular
      reconstruction with epidural anesthesia. INTERVENTIONS: At the beginning of
      surgery, 10 patients received 3 mg of epidural morphine, and the other 10
      patients received normal saline epidurally. All patients received midazolam
      intravenously in bolus doses and as a continuous infusion to maintain a steady
      state of sedation throughout surgery. MEASUREMENTS AND MAIN RESULTS: There was no
      difference between the dose of midazolam required to maintain sedation in the two
      groups during the first 3 hours of the study. Beyond the third hour, the
      midazolam dose required to maintain the same level of sedation was significantly
      higher in the placebo group than in the epidural morphine group (p = 0.05).
      CONCLUSION: An analgesic dose of epidural morphine, after a latent period of 3
      hours, may decrease the dose of midazolam required for sedation using regional
      anesthesia.

PMID- 8142093
TI  - Spinal anesthesia using a 1:1 mixture of bupivacaine and tetracaine for
      peripheral vascular surgery.
AB  - STUDY OBJECTIVE: To present our preliminary experience using three doses of an
      equimilligram mixture of 1% tetracaine and 0.75% bupivacaine in 8.25% dextrose
      for spinal anesthesia in patients undergoing peripheral vascular surgery.
      SETTING: Operating and recovery rooms at a university medical center. PATIENTS:
      60 patients who received femoral popliteal or femoral distal bypass with spinal
      anesthesia. INTERVENTIONS: All patients had intravenous cannulae inserted and
      received lactated Ringer's solution. There were no bolus infusions of fluid
      preanesthesia. Fluid administration occurred at a rate of 8 to 15 ml/kg/hr, with
      additional fluid and inotropic drugs administered to treat hypotension. Oxygen
      (O2) was delivered by nasal cannula, and peripheral O2 saturation was monitored.
      Blood pressure (BP) was monitored every 1 to 5 minutes using an automatic BP
      device, and ECG was displayed continually. MEASUREMENTS AND MAIN RESULTS:
      Initially, 8 patients received a dose of 15 mg of each drug combined with 0.2 mg
      of epinephrine injected in a 20-degree head-up tilt. Because the duration of
      anesthesia was prolonged, subsequent patients received 12 mg of each drug mixed
      with 0.2 mg of epinephrine for cases in which an extended duration was predicted
      and 10 mg of each drug plus epinephrine for proximal first-time bypasses. With
      mixtures of 15 mg, 12 mg, and 10 mg of each drug plus epinephrine, a mean
      duration of approximately 300 minutes of surgically acceptable anesthesia was
      obtained. As the dose was decreased, the SD increased. There was a 0% failure
      rate for the spinal anesthetics at doses of 15 mg and 12 mg of each drug and a
      19.5% failure rate at a dose of 10 mg of each drug. In each case, the rapid onset
      of a sensory blockade regressed in a standard and predictable fashion. The
      decline in BP and the use of inotropic and vasoconstrictive drugs were comparable
      to those in previously published reports of spinal anesthetics using single drug
      techniques with smaller doses. In none of the patients were there any untoward
      cerebrovascular or neurologic events, nor were there any clinically evident
      episodes of coronary insufficiency. CONCLUSION: Spinal anesthesia using
      bupivacaine and tetracaine mixed in a single-injection technique can last 5 hours
      at the T12 level without added untoward effects when compared with lower-dose
      spinal anesthetics.

PMID- 8142094
TI  - Intravenous ketorolac as an adjunct to patient-controlled analgesia (PCA) for
      management of postgynecologic surgical pain.
AB  - STUDY OBJECTIVE: To determine whether intravenous (IV) doses of ketorolac
      tromethamine provide safe and effective augmentation of postsurgical analgesia
      for patients using IV patient-controlled analgesia (PCA) with morphine. DESIGN:
      Randomized, double-blind, placebo-controlled, dose-response evaluation. SETTING:
      Patient care unit at a university medical center. PATIENTS: 62 ASA physical
      status I-III females recovering from intra-abdominal gynecologic surgery with
      general anesthesia who requested postoperative PCA. INTERVENTIONS: Following
      initial pain assessment in the recovery room, patients were randomized to receive
      either IV saline (placebo) followed by IV saline every 6 hours (Group 1); IV
      ketorolac 30 mg loading dose followed by IV ketorolac 15 mg every 6 hours (Group
      2); or IV ketorolac 60 mg loading dose followed by IV ketorolac 30 mg every 6
      hours (Group 3). All patients were provided IV PCA, which was programmed to
      provide 1.2 mg of morphine with a 6-minute lockout interval. MEASUREMENTS AND
      MAIN RESULTS: Visual analog scale (VAS) resting pain and satisfaction scores were
      measured every 2 to 12 hours. Cumulative PCA with morphine and the frequency and
      severity of side effects also were assessed. IV ketorolac showed no clinically
      significant side effects. Group 2 patients experienced significant reductions in
      VAS resting pain scores (p < 0.05), and a trend toward decreased morphine self
      administration in both active groups was noted. Group 2 and Group 3 patients
      reported greater satisfaction with postsurgical analgesia than Group 1 patients.
      (p < 0.05). CONCLUSIONS: IV ketorolac used as an analgesic adjunct provided safe
      and effective augmentation of PCA with morphine in patients recovering from intra
      abdominal gynecologic surgery.

PMID- 8142095
TI  - Management of tracheobronchial and esophageal foreign bodies in children: a
      survey study.
AB  - STUDY OBJECTIVE: To assess the current anesthetic management for aspiration of a
      foreign body into the airway and esophagus of a young child. DESIGN:
      Questionnaire study. MEASUREMENTS AND MAIN RESULTS: A questionnaire regarding
      choice of induction technique in a variety of foreign body clinical scenarios was
      sent to 1,342 anesthesiologists, all members of the Society for Pediatric
      Anesthesia. The foreign body, either a coin (penny) or a safety pin (open), was
      positioned on radiography in a variety of anatomic locations. Depending on the
      foreign body location, the patient was either asymptomatic or exhibited symptoms.
      Participants indicated their choice of induction for each situation. Of the 1,342
      questionnaires mailed, there were 838 respondents (62.4%). Coins and pins in the
      gastroesophageal tract were managed mostly by a rapid-sequence induction (p <
      0.001). Coins and pins at all levels in the tracheobronchial tree were managed
      most often by a mask induction with no cricoid pressure (p < 0.001). Although
      14.5% of respondents chose awake and sedated technique for a foreign body in the
      supraglottic area, few chose this technique for a foreign body in other
      locations. The type of object did not affect the choice of drugs for induction of
      anesthesia in most anatomic locations. Respondents with limited pediatric
      anesthesia experience used inhalation induction much less often than did those
      with more experience. Multiple-logistic regression analysis showed that both
      number of years in practice and type of practice (university, private, hybrid)
      were predictors for the induction. CONCLUSIONS: These data indicate that
      inhalation induction is favored most often for removal of foreign bodies in the
      airway, while intravenous induction is preferred for removal of foreign bodies in
      the gastroesophageal tract. In addition, practice type, greater percentage of
      time spent in pediatric anesthesia, and greater experience are related to a
      higher likelihood of inhalation induction.

PMID- 8142096
TI  - Cervical radiculopathy treated by infusion of epidural analgesics in homebound
      patients.
AB  - STUDY OBJECTIVE: To determine the efficacy and safety of administering low-dose
      analgesic infusions through cervical epidural catheters. DESIGN: Retrospective
      review of medical records. SETTING: Community hospital. PATIENTS: 14 ambulatory
      adult patients with chronic cervical radiculopathy due to posttraumatic or
      osteoarthritic degenerative disk disease persisting after steroid epidural
      blocks. INTERVENTIONS: 42 catheters were inserted into the cervical epidural
      space and infused with low-dose fentanyl-bupivacaine mixtures continuously for 2
      to 17 days. To prevent side effects, the optimal dose was reached by upgrade
      adjustments. After catheter insertion, patients were observed for 6 to 21 days
      for dose adjustment, then discharged home and followed by homecare nurses. After
      removal of catheters, patients were followed for 8 to 10 days. If pain intensity
      returned to control levels, other treatment was initiated. MEASUREMENTS AND MAIN
      RESULTS: After each catheter treatment, pain intensity was reduced in 79% of the
      cases. Upon completion of the therapy, 5 patients had 50% to 75% of their pain
      reduced. Eight patients experienced 75% or more reduction of their original pain.
      The most common complications were nausea (35.7%) and pruritus (27%). One case of
      cellulitis was treated with antibiotics. There were no instances of respiratory
      compromise. CONCLUSIONS: Patients with chronic persistent cervical radiculopathy
      pain were effectively treated with infusion of analgesics through epidural
      catheters for 2 to 17 days while they were at home.

PMID- 8142097
TI  - Radiation exposure of anesthesiologists.
AB  - STUDY OBJECTIVE: To determine the level of radiation exposure of
      anesthesiologists in the operating rooms and cardiac catheterization laboratory.
      DESIGN: Prospective study of all anesthesia fellows. SETTING: Operating rooms
      (ORs) and radiology department of a tertiary care pediatric hospital. SUBJECTS:
      Anesthesiologists caring for patients in a pediatric hospital requiring
      anesthesia or monitored anesthesia care. (Patients were not directly studied.)
      MEASUREMENTS AND MAIN RESULTS: Anesthesiologists wore standard radiation safety
      film badges, which were sensitive to cumulative doses of radiation greater than
      10 mrem. In the ORs, anesthesiologists were exposed to less than 10 mrem/mon. In
      the cardiac catheterization laboratory, they had dosimetric readings that ranged
      from 20 to 180 mrem/mon and frequently exceeded the guidelines for nonradiation
      workers. CONCLUSIONS: There is no need for routine dosimetric monitoring of
      anesthesiologists working in the OR setting, since this is associated with
      negligible radiation exposure. Monitoring of radiation film badges should be
      considered for anesthesiologists who frequently work in fluoroscopy areas, such
      as the cardiac catheterization laboratory. All personnel working near radiation
      sources should wear appropriate shielding and, whenever patient safety permits,
      distance themselves as far as possible from the source of radiation.

PMID- 8142098
TI  - The frequency of postdural puncture headache in obstetric patients: a prospective
      study comparing the 24-gauge versus the 22-gauge Sprotte needle.
AB  - STUDY OBJECTIVE: To compare the frequency of postdural puncture headache (PDPH)
      in obstetric patients when using the 24-gauge or the larger 22-gauge Sprotte
      needle. DESIGN: Prospective, randomized study. SETTING: Four hospitals. PATIENTS:
      375 ASA physical status I and II cesarean section and postpartum tubal ligation
      patients. INTERVENTIONS: Obstetric patients were randomly assigned to receive
      spinal anesthesia via a midline dural puncture using the 24-gauge or the 22-gauge
      Sprotte needle. MEASUREMENTS AND MAIN RESULTS: The rate of PDPH was determined by
      a postoperative visit by the anesthesiologist as well as questioning patients by
      telephone 1 week or more after discharge. In the 24-gauge Sprotte needle group (n
      = 186), 2 mild and 1 moderate PDPHs were reported, for an overall rate of 1.61%.
      In the 22-gauge Sprotte needle group (n = 189), 2 mild and 1 moderate PDPHs were
      reported, for an overall rate of 1.59%. All headaches except 1 resolved within 72
      hours with conservative treatment. One patient from the 22-gauge Sprotte needle
      group required an epidural blood patch. There were no failed blocks in either
      group. CONCLUSIONS: Our results suggest that the 22-gauge Sprotte needle, when
      compared with the smaller 24-gauge Sprotte needle, can be used in obstetric
      patients without increasing the frequency of PDPH.

PMID- 8142099
TI  - Intercostal nerve block for lumpectomy: superior postoperative pain relief with
      bupivacaine.
AB  - STUDY OBJECTIVES: To investigate whether equipotent doses of lidocaine and
      bupivacaine were equally effective for intercoastal nerve blockade (ICNB) and
      whether a lower amount of lidocaine would be comparably effective. To see whether
      plasma levels of lidocaine with and without epinephrine and of plain bupivacaine
      would reach toxic ranges. Finally, to evaluate the duration of postoperative
      analgesia following general anesthesia and regional anesthesia with two different
      local anesthetics. DESIGN: Randomized, double-blind study, with control group
      administered general anesthesia. SETTING: Gynecologic operating room of a
      university hospital. PATIENTS: 48 adult ASA physical status I and II otherwise
      healthy patients undergoing lumpectomy. INTERVENTIONS: 36 patients received ICNB
      of T3-T6 unilaterally using either 4 ml/segment of 1.5% lidocaine with
      epinephrine 3.75 micrograms/ml (n = 10, Group A), 4 ml/segment of 2% lidocaine
      with epinephrine 5 micrograms/ml (n = 13, Group B), or 4 ml/segment of plain 0.5%
      bupivacaine (n = 13, Group C). The control group consisted of 12 patients (Group
      D) who received a general anesthetic using propofol, alfentanil, and nitrous
      oxide in oxygen for induction and maintenance of anesthesia. MEASUREMENTS AND
      MAIN RESULTS: In all three ICNB groups, the highest plasma concentrations were
      reached after 5 to 10 minutes following ICNB--i.e., a lidocaine plasma level of
      2.77 +/- 0.5 micrograms/ml (mean +/- SEM) in Group A, a lidocaine plasma level of
      2.78 +/- 0.2 micrograms/ml in Group B, and a bupivacaine plasma level of 1.44 +/-
      0.2 micrograms/ml in Group C. There were no significant differences in plasma
      levels between 1.5% lidocaine and 2% lidocaine. For the first 90 minutes after
      surgery, higher postoperative pain scores were found in the control group than in
      the ICNB groups. Notably longer-lasting postoperative pain relief was achieved
      with plain bupivacaine. The number of women requiring postoperative analgesic
      medication, the time of first request, and the total amount of analgesic drugs
      administered during the 24 hours postoperatively were significantly lower in the
      regional anesthesia groups than in the general anesthesia group (p < 0.05).
      CONCLUSIONS: ICNB is an alternative to general anesthesia for female breast
      surgery. Both lidocaine with epinephrine and plain bupivacaine in the doses used
      did not raise venous plasma concentrations to levels considered potentially
      toxic. With respect to duration of postoperative pain relief and analgesic drug
      request, the local anesthetics (in particular, bupivacaine) were found to be
      superior to general anesthesia.

PMID- 8142100
TI  - Bacterial endocarditis prophylaxis: what is recommended and what is practiced?
AB  - STUDY OBJECTIVE: To determine how often pediatric anesthesiologists follow the
      American Heart Association (AHA) recommendations for the administration of
      prophylactic antibiotics to prevent bacterial endocarditis (BE). DESIGN:
      Questionnaires mailed to all members of the Society for Pediatric Anesthesia
      regarding their use of antibiotics to prevent BE. SETTING: Anesthesia department
      at a university-affiliated children's hospital. MEASUREMENTS AND MAIN RESULTS:
      898 questionnaires were mailed, and 465 questionnaires were returned, yielding a
      response rate of 52%. When anesthesiologists administer BE prophylaxis
      intravenously (IV), they perform an inhalation anesthetic 76% of the time prior
      to establishing IV access. Ninety percent of the respondents stated that if
      administration of antibiotics occurs after a mask induction, they do not delay
      incision or instrumentation for 30 minutes. Therefore, respondents do not follow
      AHA recommendations for BE prophylaxis 55% of the time. Of the 465 respondents,
      only 4 recalled pediatric patients who developed perioperative BE. CONCLUSIONS:
      The majority of anesthesiologists responding to this survey routinely do not
      follow the current AHA recommendations for BE prophylaxis when caring for
      children. Since there are no studies demonstrating that administering antibiotics
      30 minutes prior to invasive procedures is more effective than administering
      antibiotics immediately prior to invasive procedures, it may be appropriate to
      follow a time sequence that is more comfortable and convenient for pediatric
      patients. We believe that a reconsideration of the current AHA recommendations
      for BE prophylaxis is warranted.

PMID- 8142101
TI  - Metal anesthesia circuit components stop the progression of laser fires.
AB  - STUDY OBJECTIVE: To determine whether metallic Y-pieces and elbows would halt the
      progression of a laser-induced endotracheal tube fire. DESIGN: A segment of
      polyvinyl chloride endotracheal tube was attached to either an all-plastic
      anesthesia circle breathing system (n = 5) or a circuit consisting of a metal Y
      piece and elbow with plastic hoses (n = 5). In each case, an Nd-YAG laser was
      used to ignite the endotracheal tube segment and attached anesthesia circuit as 5
      L/min of oxygen was flowing through them. SETTING: Research laboratory of a
      university-affiliated metropolitan medical center. MEASUREMENTS AND MAIN RESULTS:
      The flames from the endotracheal tubes burned through the 22 mm hoses that were
      part of the all-plastic circuits in 49.5 +/- 8.8 seconds (mean +/- SD). In none
      of the trials with the metal components did the fire advance beyond the
      endotracheal tube's 15 mm adapter. CONCLUSIONS: Metal circuit components halt the
      progression of laser-induced endotracheal tube fires toward the anesthesia
      machine.

PMID- 8142102
TI  - Anesthesia in a patient with acute respiratory insufficiency due to relapsing
      polychondritis.
AB  - We report on a male patient with advanced relapsing polychondritis (RP), who was
      hospitalized for an ophthalmologic intervention. He had to undergo a tracheostomy
      with general anesthesia due to respiratory decompensation. RP is a rare systemic,
      inflammatory, and destructive disease of the cartilaginous structures leading to
      multiple functional disorders in the affected organs. Involvement of the
      tracheobronchial tract may cause severe respiratory problems and even life
      threatening respiratory insufficiency. Treatment consists of corticoids,
      chemotherapy, antirheumatics, and surgical intervention. Anesthesiologic
      management requires careful preoperative evaluation of vital organ functions, in
      particular respiration, so that the anesthetic approach can be tailored to the
      individual needs of each patient.

PMID- 8142103
TI  - Electrocardiographic artifact corrected with intravenous nitroglycerin.
AB  - A number of conditions can cause ST segment changes exclusive of myocardial
      ischemia, and nitroglycerin has been administered in such cases. We report a case
      of artifactual ST depression that was managed with intravenous nitroglycerin. In
      this case, the cause of the ECG artifact might have been the apical heartbeat.

PMID- 8142104
TI  - Cardiopulmonary arrest in the pregnant patient: a report of a successful
      resuscitation.
AB  - We report the case of a pregnant patient who suffered cardiac arrest and was
      initially unresponsive to resuscitative measures. Prompt emergent cesarean
      delivery of the infant was carried out, and both mother and infant were then
      successfully resuscitated. We believe that prompt cesarean delivery is the key to
      maternal and infant survival in such cases.

PMID- 8142105
TI  - Anesthetic management of the patient scheduled for head and neck cancer surgery.
AB  - For the patient scheduled for head and neck cancer surgery, careful assessment of
      the airway demonstrates the most appropriate course of action for securing the
      airway before surgery begins. Often the patient may be anesthetized safely before
      intubation of the trachea. The patient may require an awake examination of the
      airway under sedation and topical analgesia or an awake fiberoptic intubation
      before the induction of general anesthesia. To secure the airway in some
      patients, a tracheostomy may be needed. After the operation, extubation of the
      trachea requires careful attention and may be even more of a challenge than the
      original intubation. Current principles and techniques for the anesthetic
      management of the patient undergoing head and neck cancer surgery are reviewed.
      Emphasis is placed on avoiding the airway problems associated with this kind of
      surgery.

PMID- 8142106
TI  - Submandibular endotracheal intubation in panfacial fractures.

PMID- 8142107
TI  - Penetration and percutaneous absorption of topical retinoids. A review.
AB  - Topical retinoids are therapeutically active at low pharmaceutical
      concentrations, i.e. in essence lack of penetration is not a problem. Thus
      studies on the cutaneous pharmacokinetics focus on the distribution pattern in
      the skin, the penetration pathways, the cutaneous metabolism, the systemic body
      load and the mode of excretion. Two basically different pathways have to be taken
      into account: the transepidermal pathway, which gives rise to a typical
      epidermal/dermal concentration gradient and which is certainly part of the mode
      of action in disorders of keratinization, and the transfollicular pathway, which
      sheds some light on the activity in follicular disorders like acne. The cutaneous
      part of the pharmacokinetics of retinoids depends largely on their chemical
      structure and thus differs. However, common features are relatively high
      cutaneous concentrations, whereas the spillover to the systemic compartment
      appears to be slow and small, giving rise to low or hardly detectable bodyloads.
      Concerning pharmacokinetics topical application of retinoids presents major
      advantages over systemic medication. They can be targeted to the intended site of
      action, furthermore systemic toxicity is of much lesser concern.

PMID- 8142108
TI  - Pharmacological effects of retinoids on skin cells.
AB  - Retinoids exert profound pleiotropic effects in skin, affecting many aspects of
      cell differentiation and proliferation. For this reason, retinoids have prominent
      pharmacological effects on major skin cells (keratinocytes, dermal fibroblasts,
      melanocytes, sebocytes) and have shown great potential as therapeutic agents in
      dermatology. In keratinocytes, retinoids induce proliferation, resulting in
      epidermal hyperplasia. Retinoids also modulate epidermal differentiation,
      however, many of the suppressive effects of retinoids observed in vitro do not
      occur in vivo. Dermal fibroblasts are important target cells of retinoids and are
      stimulated to produce extracellular matrix proteins, particularly when skin is
      damaged by wounding, ultraviolet radiation or glucocorticoids. Retinoids regulate
      pigmentation and can lighten hyperpigmented skin in animals and humans. Studies
      with cultured melanocytic cells show that tyrosinase activity is reduced by
      retinoids. The powerful sebosuppressive effect of some retinoids, such as 13-cis
      retinoic acid, demonstrates that sebocyte differentiation is altered by
      retinoids. Retinoids inhibit proliferation and lipid synthesis in cultured human
      sebocytes and alter their keratin expression.

PMID- 8142109
TI  - Therapy with vitamin A acid.

PMID- 8142110
TI  - Embryotoxicity and teratogenicity of topical retinoic acid.
AB  - All-trans-retinoic acid is a potent developmental toxicant in all species
      examined. The teratogenic risk of topical all-trans-retinoic acid is reviewed.
      Experimental studies are limited because of the high maternal toxicity, including
      skin irritation, with doses below those resulting in significant teratogenic
      response with other application routes, such as oral application. The maximal
      systemic availability reported for transdermal exposure of all-trans-retinoic
      acid was 5-6% in the rat, 9.6% in the monkey (48% with dermatitic skin) and 5-7%
      in the human. Oral administration of threshold teratogenic doses of all-trans
      retinoic acid (6 mg/kg/day) to Wistar rats and Swiss hare rabbits resulted in
      embryonic area under the concentration time curve levels (approximately 1,000
      ng.h/g) which were 2- to 4-fold higher than the endogenous all-trans-retinoic
      acid levels; corresponding maternal plasma area under the concentration time
      curve values were 98 and 321 ng.h/ml in rat and rabbit, respectively. The 4-oxo
      metabolite was also found in maternal plasma and embryo. Large, controlled
      studies on the possible developmental toxicity of topical all-trans-retinoic acid
      in the human are not available. Isolated case reports appeared in the literature
      claiming teratogenic outcome resembling effects after oral isotretinoin use or
      those observed in experimental studies with oral or parenteral all-trans-retinoic
      acid administration. The dose absorbed from daily cosmetic or therapeutic
      application of all-trans-retinoic acid is expected to be below 0.015 mg/kg, which
      is at least 30-fold lower than the lowest teratogenic dose of isotretinoin in the
      human. Topical all-trans-retinoic acid application did not appreciably alter
      endogenous plasma retinoid levels. The influence of nutrition, diurnal variation
      and in particular oral vitamin A supplements are more important determinants of
      plasma retinoic acid compounds than topical all-trans-retinoic acid. These
      results imply a low risk of therapeutic or cosmetic application of topical all
      trans-retinoic acid. However, the highly specific spatial and temporal
      distribution of binding proteins and nuclear receptors in the embryo suggests
      that even small alterations in endogenous levels of all-trans-retinoic acid in
      the embryo may alter crucial developmental processes such as morphogenes; this
      aspect should be further investigated.

PMID- 8142111
TI  - Evaluation of the teratogenic risk of cutaneously administered retinoids.
AB  - In current cutaneous retinoid therapy systemic exposure is low and the risk of
      teratogenesis appears to be limited. However, new indications, altered posologies
      and the introduction of new synthetic retinoids demand continuous assessment of
      the teratogenic risk. Teratogenicity testing of new substances in animals is only
      of value if accompanied by detailed pharmacokinetic analysis to establish the
      relationships between the levels of parent compound and metabolite in both
      maternal plasma and fetal tissues and teratogenic events. This information should
      be compared to the maximum of relevant pharmacokinetic data which can be
      ethically obtained in man or from human tissues. The presence or absence of
      teratogenic effects following cutaneous administration of retinoids in animals
      has, as such, little direct bearing on the risk in man. Two special cases exist
      where teratogenic risk can be evaluated directly in man without reference to
      animal studies. The first concerns substances whose teratogenic potential has
      been established in man by other routes of administration permitting a comparison
      with the cutaneous route on a pharmacokinetic basis. The second concerns the
      cutaneous administration of endogenously occurring substances and their eventual
      disturbance of systemic retinoid equilibrium.

PMID- 8142112
TI  - Clinical aspects of topical retinoids.
AB  - Topical retinoids have been employed in dermatology since the 1960s to treat a
      wide variety of cutaneous disorders. This review focuses on three areas in which
      retinoids have had their greatest impact: acne vulgaris, photoaging and cutaneous
      neoplasia. The pharmacology of the available topical retinoids, their mechanism
      of action and the history of their use in these disorders are discussed.

PMID- 8142113
TI  - Adapalene, a new chemical entity with retinoid activity.
AB  - Adapalene is a novel chemical entity which, in terms of pharmacology, behaves
      similar to tretinoin, but is chemically and photochemically stable. It has a
      particular selectivity profile for the known nuclear retinoic acid receptors with
      low affinity for RAR alpha and no transactivating potential for RXR alpha. This
      receptor profile could imply that adapalene, in contrast to tretinoin, affects
      the terminal differentiation pathway of epidermal cells rather than their
      proliferation. Furthermore, adapalene does not bind to members of the cellular
      retinoic acid binding protein family. Adapalene has comedolytic activity in the
      topical rhino mouse model. It exerts a moderate-to-potent anti-inflammatory
      effect in a series of in vitro and in vivo models. In comparative clinical
      studies involving 72 acne patients, the efficacy of adapalene was comparable, if
      not superior, to tretinoin, but adapalene was better tolerated. The data reviewed
      in this paper indicate that adapalene should be particularly beneficial in the
      treatment of acne.

PMID- 8142114
TI  - Topical retinoic acid for photoaging: clinical response and underlying
      mechanisms.
AB  - Photoaging is primarily composed of wrinkling, mottled hyperpigmentation and a
      tactile roughness of the skin, all three of these parameters improve following
      use of topical retinoids. It appears that smoothening of the skin results from a
      combination of epidermal changes including thickening, stratum corneum compaction
      and glycosaminoglycan deposition. Lightening of actinic lentigines and mottled
      hyperpigmentation correlates with a reduction in epidermal melanin content maybe
      resulting from inhibition of tyrosinase activity. Effacement of wrinkling in mice
      correlates with new collagen synthesis, and there is evidence that this is also
      the case in humans. An irritant dermatitis is a feature of retinoid-treated skin
      but this diminishes in severity during treatment despite continued improvement in
      photoaging. Thus it is unlikely that irritation per se is responsible for
      clinical improvement.

PMID- 8142115
TI  - Treatment of photoaged skin with topical tretinoin.
AB  - Once-daily application of tretinoin to photodamaged facial skin for 0-12 months
      results in substantial clinical and histologic improvement. As regards
      appearance, fine wrinkles become effaced, dyspigmentations fade, surface becomes
      smooth and develops a 'rosy glow'. Histologically, atrophy and dysplasia of the
      epidermis are completely corrected. New collagen is laid down subepidermally
      along with the development of new small vessels (angiogenesis). Mesenchymal
      dermal cells become more numerous and larger. The sum of changes is toward more
      youthful skin.

PMID- 8142116
TI  - Signal transduction by retinoid receptors.
AB  - Vitamin A derivatives (retinoids) affect a large variety of fundamental
      biological processes. Understanding of the signaling mechanism has been greatly
      advanced by the cloning of specific retinoid receptors. These regulatory proteins
      belong to the steroid/thyroid hormone nuclear receptor superfamily. Two types of
      retinoid receptors have been identified, the retinoic acid receptors (RAR alpha,
      beta and gamma) and the retinoid X receptors (RXR alpha, beta, and gamma).
      Similar to the steroid hormone receptors, the retinoid receptors bind to specific
      DNA sequences that have diad symmetries. However, the RARs require
      heterodimerization with RXRs for efficient DNA binding and gene regulation, while
      the RXRs can bind to DNA and function as homodimers in the presence of 9-cis
      retinoic acid. In addition, RXRs can form heterodimers with thyroid hormone
      receptors and the vitamin D3 receptor and other receptors. Thus the RXRs have a
      very central role in serving as a partner for several hormone and vitamin
      receptors and thus may allow cross talk between different hormone signals.
      Retinoid responses can be restricted by the COUP-TF orphan receptors which bind
      to overlapping DNA sequences. Besides the classical way of action via DNA
      binding, the retinoid receptors can also interfere with other signaling pathways
      by interacting with the transcription factor AP-1. The advances made in
      understanding the mechanism of action of retinoids promise to contribute to the
      understanding and control of physiological responses and diseases.

PMID- 8142117
TI  - The prognostic value of epidermal growth factor receptor (EGFR) in breast cancer
      patients. Results of a follow-up study on 149 patients.
AB  - The expression of epidermal growth factor receptor (EGFR) in breast cancer
      patients was correlated to the disease-free survival. The study included 149
      breast cancer patients. The mean follow-up time was 4.2 years. There was an
      inverse correlation between EGFR and estrogen receptor (p < 0.003) and
      progesterone receptor (p < 0.013). Subdivision of EGFR showed that patients with
      EGFR > or = 0.60%, regarded as EGFR positive, had a worse prognosis than patients
      with EGFR binding < 0.60%, regarded as EGFR negative (p = 0.004). In the ER
      negative group, EGFR positive patients had a shorter relapse-free time than
      patients with EGFR negative cancer (p < 0.009). The same subdivision among ER
      positive patients showed no statistically significant difference.

PMID- 8142118
TI  - Serum soluble interleukin-2 receptor in colorectal cancer.
AB  - Preoperative serum soluble interleukin-2 receptor (IL-2R) levels were measured in
      patients with colorectal cancer, and correlated with various factors as stage,
      lymph node metastasis, liver metastasis, grade, serum CEA and IAP
      (immunosuppressive acidic protein). The levels of serum soluble IL-2R in Dukes
      stage C were significantly higher than in normal control and in Dukes stage A.
      Serum levels were also significantly higher in patients with lymph node
      metastasis than in patients without such metastasis, and in IAP positive patients
      compared to IAP negative patients. Preoperative serum IL-2R levels thus seem to
      reflect the stage of the disease.

PMID- 8142119
TI  - Cell kinetics of head and neck squamous cell carcinomas. Prognostic implications.
AB  - Forty-three squamous cell carcinomas of the head and neck region were in vivo
      labelled with the thymidine analogue iododeoxyuridine. Combined flow cytometric
      (FCM) and immunohistochemical (IHC) analysis was performed, and the following
      parameters calculated: labelling index (LI), S-phase time (TS) and potential
      tumor doubling time (Tpot). Complete FCM and IHC analyses could successfully be
      performed in 31 cases, showing a median LI of 13.6% with FCM and 9.1% with IHC. A
      correlation achieved between LI/FCM and LI/IHC was due to the aneuploid cases,
      whereas the diploid cases showed no such correlation. Data indicated that Tpot
      calculated with LI from IHC (Tpot/IHC) might be a prognostic factor, in contrast
      to Tpot determined using LI/FCM.

PMID- 8142120
TI  - O6-methylguanine-DNA methyltransferase activity in cerebral gliomas. A guidance
      for nitrosourea treatment?
AB  - The activity of O6-methylguanine-DNA methyltransferase (O6-MT), which removes O6
      methyl residues from O6-methylguanine-DNA leading to cell death, has been
      reported to correlate with sensitivity to nitrosoureas used for chemotherapy of
      gliomas. We determined O6-MT activity in tumors and matched brain tissue from
      patients with gliomas. Histological diagnoses were: six malignant astrocytomas,
      two glioblastomas, two oligodendrogliomas, one ependymoma, and one
      medulloblastoma. In all cases but one, the activity ranged widely from 39 to 258
      fmol/mg protein extract. The wide range of activity of the tumor tissue may
      indicate varying degree of sensitivity to nitrosoureas. The activity of brain
      tissue, available from the peritumoral region of five cases, varied between 38 to
      415 fmol/mg. Four of the five regions showed a higher value than the respective
      tumor, and one showed a lower value.

PMID- 8142121
TI  - Diagnostics of malignant lymphomas with ultrasound guided 1.2 mm biopsy-gun.
AB  - In a retrospective analysis of 129 ultrasound-guided biopsy-gun biopsies (USGB)
      from patients with known or suspected malignant lymphoma, a histopathological
      diagnosis was obtained in 101 (78%) instances and no further procedures for
      histological verification were required. In the 28 cases with initially non
      diagnostic results, 14 new USGBs were performed and a diagnosis was obtained in
      11. Thus, a total success rate of 87% was achieved. The correct diagnosis was
      confirmed with either surgery, autopsy, or radiological or clinical follow-up
      (median 40 months). The diagnoses were categorised as Hodgkin's disease and high
      grade or low-grade non-Hodgkin's lymphoma. Further subtyping of the lymphoma was
      possible in a few cases only. Immunohistochemistry was utilised only in a minor
      proportion of the cases (25/129), but refined the diagnosis in several instances.
      The biopsy-gun method was safe and minor adverse effects were seen in two
      patients only.

PMID- 8142122
TI  - Hepatic intra-arterial administration of doxorubicin and degradable starch
      microspheres. A pharmacokinetic study in the rat.
AB  - Urinary concentration of doxorubicin and its active metabolite doxorubicinol was
      followed in two groups of rats after hepatic intra-arterial injection of a single
      dose of 6 mg/kg doxorubicin or the same dose combined with 30 mg/kg Spherex
      (DSM). Urinary samples were collected during five days following administration.
      The concomitant DSM administration caused a significant decrease of the
      cumulative urinary excretion of intact doxorubicin; average five days of
      cumulative values were 73 and 103 micrograms respectively in the group with and
      without DSM. This indicates a DSM-induced reduction in systemic drug exposure.
      The elimination rates of doxorubicin or its active metabolite were not influenced
      by DSM. The decrease in excretion of the parent drug was not due to an
      interaction between the drug and DSM as evident by examining the binding of
      doxorubicin to DSM in vitro. Instead regionally altered drug distribution seems a
      plausible explanation to the reduction.

PMID- 8142123
TI  - Squamous cell carcinoma of the maxillary sinus and the oral part of the upper
      jaw. Comparison of treatment results.
AB  - The treatment results were compared in 77 patients with maxillary sinus squamous
      cell carcinoma (MC) and 53 patients with squamous cell carcinoma arising from the
      oral part of the upper jaw (OC). Both sets of patients received radiotherapy
      alone, or radiotherapy combined with surgery and/or chemotherapy. Computerized
      tomography was useful for the definition of the treatment volume. Intraarterial
      chemotherapy was given in 89 of 130 patients and in these patients the total
      radiation dose was reduced by about 10 Gy. No difference was found in the 5-year
      survival rate between the MC (65%) and the OC (66%) groups. The cumulative
      incidence of local failure was higher in MC (36%) than in OC (26%), whereas the
      ultimate incidence of neck node metastasis was higher in OC (43%) than in MC
      patients (18%). Half of the inoperable patients (9/18) were older than 80 years
      and had contraindications to anaesthesia and major surgery. The local recurrence
      rate was high in the inoperable MC patients (6/8). Contralateral sinus cancers
      occurred in 4 patients in the MC group.

PMID- 8142124
TI  - Acute and delayed effects of radiotherapy in patients with oesophageal squamous
      cell carcinoma treated with chemotherapy, surgery and pre- and postoperative
      radiotherapy.
AB  - Among 73 patients with oesophageal squamous cell carcinoma treated with
      chemotherapy (cisplatin + 5-fluorouracil), surgery and pre- and postoperative
      radiotherapy, the 1-year survival rate was 68% and the 5-year rate 26%. The
      treatment was well tolerated, though there were 11 cases of pericardial or
      pleural effusion, in all of which the effusion was benign and could be
      successfully treated with pleural aspiration and/or pleurodesis,
      pericardiocentesis, or in one case pericardectomy.

PMID- 8142125
TI  - Overview of U.S. National Cancer Institute (USNCI) chemoprevention research.
AB  - The National Cancer Institute's (NCI) chemoprevention plan employs a strategy of
      basic and epidemiologic studies, followed by a structured preclinical process to
      bring chemopreventive agents into clinical testing. The field of chemoprevention
      is progressing rapidly and has reached the point where a coordinated
      international approach for large-scale trials would be useful. At present, NCI is
      sponsoring nine large trials (over $1 million per year per trial); in addition,
      nine agents are in phase I or II clinical testing. A number of these agents
      should be ready soon for phase III testing. Resources required for large-scale
      trials compel greater attention to efficient trial design, concept development
      and review, priority setting, management, budgeting, and collaboration.

PMID- 8142126
TI  - Surgery and postoperative radiotherapy and radiotherapy alone in T3-T4 cancers of
      the pyriform sinus. Treatment results and patterns of failure.
AB  - Fifty-four patients with T3-T4 squamous cell carcinomas of the pyriform sinus
      were treated between 1976 and 1990. Surgery with postoperative radiotherapy (n =
      32) was the treatment of choice. Radical radiotherapy was used in patients with
      contraindications for surgery or with inoperable tumors and in patients who
      refused surgery. The local control rate was significantly higher in the combined
      treatment group (31/32; 97%) than in the group treated with radical radiotherapy
      (14/22; 64%) which consisted of more advanced cases. In patients who received
      radical radiotherapy, the highest local control rates were recorded with doses of
      70 Gy and above and with the use of 2 fractions per day. There was no significant
      difference in regional control and survival rates between the treatment groups.
      New approaches are indicated to improve the prognosis of hypopharyngeal cancer.

PMID- 8142127
TI  - Oral sucralfate in acute radiation oesophagitis.
AB  - Eighty patients with carcinoma in the middle third of oesophagus and with acute
      radiation oesophagitis following external beam and intracavitary radiotherapy
      were managed by two different schedules. Group 1 (n = 40) received an antacid
      containing sodium alginate whereas Group 2 (n = 40) were given a 10% sucralfate
      suspension during 4 weeks. In Group 2, 32 patients had significant relief of
      symptoms within 7 days of treatment and most ulcers had healed by 12 days of
      treatment as seen on endoscopy. Patients in Group 1, on the other hand, showed
      little improvement of symptoms and had persistent ulcers even after 4 weeks of
      therapy. We conclude that sucralfate is useful in the management of acute
      radiation oesophagitis.

PMID- 8142128
TI  - Cryoglobulinaemia ten years before onset of lymphoma.

PMID- 8142129
TI  - Serum concentrations of insulin-like growth factor 1 in colonic neoplasia.

PMID- 8142130
TI  - Primary osteosarcoma of the breast--case report and review of the literature.

PMID- 8142131
TI  - Successful management of choriocarcinoma with pregnancy.

PMID- 8142132
TI  - Slowly growing pulmonary metastases of malignant cervical chemodectoma.

PMID- 8142133
TI  - Opportunistic strongyloides stercoralis hyperinfection in lymphoma patients
      undergoing chemotherapy and/or radiotherapy--report of a case and review of the
      literature.

PMID- 8142134
TI  - Prednimustine-induced myoclonus--a report of three cases.

PMID- 8142135
TI  - Simultaneous pulmonary carcinoma in twins--a case report and review of the
      literature.

PMID- 8142136
TI  - L5 sciatica as first symptom of a granulocytic sarcoma.

PMID- 8142137
TI  - Antigen detection in neutralization assays: high levels of interfering anti-p24
      antibodies in some plasma.

PMID- 8142138
TI  - Improbability of harmful autoimmune responses resulting from immunization with
      HIV-1 envelope glycoproteins.
AB  - Autoimmunity mediated by cross-reactive antibodies, elicited by HIV-1 envelope
      glycoproteins gp120/gp160, has been postulated to contribute to the pathogenesis
      of AIDS. Partial amino acid sequence homology between gp120/gp160 and several
      human host proteins, including MHC antigens and immunoglobulins, has been
      perceived as the basis for immunological cross-reactivity. Binding of antibodies
      from sera of HIV-1-infected individuals to selected host proteins and/or to
      synthetic peptides derived from them and the inhibitory activity of such sera in
      assays measuring the functional activity of T cells provided apparent support for
      the autoimmunity hypothesis, which is also relevant to the issue of safety of
      anti-HIV-1 vaccines. Considering the possibility that the detected autoantibodies
      may arise for reasons other than antibody responses to gp120/gp160, the
      immunological cross-reactivity between gp120/gp160 and the relevant host proteins
      was investigated using hyperimmune rabbit anti-gp120/gp160 and monoclonal
      antibodies. As determined from dilution end-point comparisons for polyclonal anti
      gp120, the cross-reactivity of anti-gp120 with CD4 was undetectable (< 10(-5)%).
      The cross-reactivity of anti-gp120/gp160 with HLA-I and HLA-II antigens was also
      undetectable (< 4 x 10(-4)%) and that with other human proteins reported to have
      partial sequence homology with gp120/gp41 was < or = 0.013%. Anti-gp120/gp160 did
      not have detectable inhibitory effects in functional assays measuring
      proliferative T cell responses. Therefore, immunization with gp120/gp160 is
      unlikely to elicit harmful autoimmune responses.

PMID- 8142139
TI  - Purification of an Escherichia coli-expressed Nef protein from the human
      immunodeficiency virus-type 2.
AB  - The entire nef gene sequence of HIV-2, NIH-Z strain, has been cloned into the
      pJL6 expression vector and used for the synthesis of a 23-kDa protein in E. coli.
      The expressed protein is a fusion between the N-terminal 13 amino acids of the
      cII gene, 8 amino acids resulting from the ligation procedure, and the 180 amino
      acids that comprise the HIV-2 Nef sequence from the NIH-Z strain. The bacterially
      expressed Nef protein has been purified to apparent homogeneity on analytical
      scale (10-20 micrograms) by a combination of sequential detergent extraction, gel
      filtration, and reversed-phase high-performance chromatography. The expressed Nef
      protein is highly susceptible to proteolysis (chymotryptic-like activity) and
      this property accounts for the low yield obtained by gel filtration and RP-HPLC.
      Larger amounts (> 100 micrograms) of the purified Nef protein have been produced
      by a purification procedure that employs sequential detergent extraction,
      chromatography on Q-Sepharose in the presence of 7 M urea, and chromatography on
      hydroxylapatite, also in 7 M urea. The purified HIV-2 Nef protein has been used
      for the production of polyclonal and monoclonal antibodies. The milder method of
      purification should facilitate structure-function studies of the Nef protein and
      its role in the life cycle of HIV.

PMID- 8142140
TI  - Nonaffinity purification of recombinant gp120 for use in AIDS vaccine
      development.
AB  - The gene encoding the major envelope glycoprotein of the HIV-SF2 isolate was
      engineered for the secretion of recombinant gp120 (rgp120SF2) from permanent
      Chinese hamster ovary (CHO) cell lines. Cellular production methods were scaled
      up and a method for purification of the secreted glycoprotein was devised. Mild
      purification conditions were selected in order to preserve the native structure
      of the protein. rgp120SF2 exhibits a molecular weight of 120 kDa in reduced or
      nonreduced SDS gels; thus the polypeptide chain is intact. Deglycosylated
      rgp120SF2 has the predicted molecular weight of the polypeptide backbone, 54 kDa.
      Gel-filtration HPLC in a nondenaturing buffer at neutral pH yields a molecular
      weight estimate of approximately 120 kDa. Purified rgp120 closely resembles
      authentic viral gp120 by several physical, chemical, and immunochemical tests.
      rgp120SF2 reacts strongly with human HIV-positive sera, monoclonal antibodies
      reactive with HIV-SF2 and HIV-MN viral envelope, and a human virus-neutralizing
      monoclonal antibody that maps to a conserved discontinuous epitope on HIV-1
      gp120. Purified rgp120SF2 forms a 1:1 molecular complex with soluble recombinant
      human CD4 (rCD4) receptor, as demonstrated by gel-filtration HPLC; binding is
      high affinity (Kd approximately 2 x 10(-9) M).

PMID- 8142141
TI  - Cellular topoisomerase I activity associated with HIV-1.
AB  - Topoisomerase I activity was detected in detergent-disrupted human
      immunodeficiency virus type 1 (HIV-1) particles. The enzyme did not require ATP
      for its conversion of SC DNA to an RC form, had divalent cation requirements
      similar to those of eukaryotic topoisomerase I, and was significantly inhibited
      by the specific topoisomerase I inhibitor camptothecin. However, camptothecin
      failed to inhibit replication of HIV in infected cells at nontoxic
      concentrations, and an active site motif for topoisomerase I could not be
      detected on the HIV genome. These results suggests that HIV does not encode a
      novel topoisomerase I, but rather packages the cellular enzyme.

PMID- 8142142
TI  - Relationship between anti-p24 antibody levels and p24 antigenemia in HIV-infected
      patients.
AB  - We studied the influence of HIV p24 antigen immune complexing with anti-p24
      antibodies on the assessment of their respective levels in HIV-positive sera.
      ELISAs were used to evaluate anti-p24 antibody levels and p24 antigenemia, with
      or without acid dissociation. Observations include the following: (1) p24
      antigenemia usually coexisted with low anti-p24 levels; (2) the p24 antigen
      concentration inversely correlated with anti-p24 antibody levels; and (3) acid
      dissociation increased the percentage of p24 antigen-positive sera, mostly when
      anti-p24 was low. In contrast, (1) antigenemia and antibodies varied
      independently in antiretroviral-treated AIDS patients, undetectable p24 antigen
      coexisting then with low anti-p24; (2) after acid dissociation, antigen was still
      undetectable in 83% of sera with high antibody levels, and in 20% with low
      antibody levels; and (3) acid dissociation did not increase low anti-p24 levels.
      Whereas the first set of observations indicates that p24 antigen and anti-p24
      antibodies can be engaged in immune complexes, the second set indicates that p24
      antigen and antibodies were not inevitably linked in such complexes: they may
      actually be indicative of two distinct biological phenomena.

PMID- 8142143
TI  - An individual with a high prevalence of a tat-defective provirus in peripheral
      blood.
AB  - The first exon of tat was sequenced from 23 provirus genomes randomly amplified
      directly from an HIV-1-infected individual's peripheral blood. Twelve of the 23
      sequences constituted a distinct subset of the quasi-species detected. This
      subset had in common two inactivating mutations in the tat gene. In addition, two
      of these defective genomes each had a unique mutation. This is the second
      instance of a defective early gene being present in a high percentage of the
      proviruses present in the PBMCs of an HIV-1-infected individual, (the first
      reported by Martins LP et al.: J Virol 1991;65:4502-4507), and suggests that
      genomes defective in an early gene can participate in the infectious spread of
      HIV-1 in vivo.

PMID- 8142144
TI  - Susceptibility of human-mouse T cell hybrids to HIV-productive infection.
AB  - Interspecies human x mouse cell hybrids were used to investigate the genetic
      basis of human permissivity to HTLV-IIIB infection. T cell hybrids between the
      mouse BW 51.47 T lymphoma line and normal, PHA-IL-2 activated, human peripheral
      mononuclear cells (PBMCs) were generated. These hybrids preferentially segregated
      human chromosomes, as assessed by phenotype and karyotype analysis. Viral
      integration occurred only in those hybrids expressing CD4+ at the cell surface.
      However, infectious progeny production was demonstrated only in two of the three
      CD4+ hybrids tested. By segregation analysis, we could correlate the absence of
      human chromosomes 1, 3, and 9 with the lack of infectious viral progeny.

PMID- 8142145
TI  - Increased susceptibility of neonatal monocyte/macrophages to HIV-1 infection.
AB  - The relative susceptibility of neonatal/cord blood monocyte/macrophages to
      productive infection with human immunodeficiency virus type 1 (HIV-1) was
      investigated. In addition, the effect of HIV-1 infection of cord blood
      monocyte/macrophages in various stages of maturation/differentiation as
      represented by differing ages of monocytes in culture was examined.
      Monocyte/macrophages were infected with two viral strains isolated and cloned
      from primary clinical isolates, each with different cell tropisms. Cord blood and
      adult monocyte/macrophages were infected with either the macrophage-tropic strain
      HIV-1(JR-FL) or the predominantly lymphocyte-tropic strain HIV-1(JR-CSF). p24gag
      antigen levels were measured in supernatants by ELISA. Cord monocyte/macrophages
      at three different ages in culture (4, 7, and 11 days) were more productively
      infected by both viral strains than were adult monocyte/macrophages infected in
      parallel. In addition, the less differentiated cells (cord and adult
      monocyte/macrophages infected after growing 4 days in culture) were more
      productively infected than were the more differentiated monocyte/macrophages
      (cells infected after growing 7 or 11 days in culture). The mechanism for this
      increased susceptibility of cord monocyte/macrophages to HIV-1 infection as
      compared to adult cells was also investigated. A measurable increase in DNA
      synthesis was found in the infected cord cells when compared to infected adult
      cells and to uninfected adult or cord cells as represented by increased
      [3H]thymidine incorporation, suggesting that increased cell proliferation of cord
      monocyte/macrophages may enhance the permissivity of infection. This article
      suggests that cord monocyte/macrophages may play an important role in the
      pathogenesis of perinatal HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142146
TI  - Reverse transcription takes place within extracellular HIV-1 virions: potential
      biological significance.
AB  - Extracellular HIV-1 virions purified from cell culture supernatants have been
      found to contain viral DNA that is the result of partial reverse transcription
      within the virus particles. Our data supported these observations and further
      indicated that the ratio of genomic RNA to viral DNA was approximately 10(3):1
      for the "strong stop" (R-U5) region and 10(5):1 for the gag region. We have shown
      that, in the absence of detergent, large amounts of DNase-resistant viral DNA can
      be synthesized within intact HIV-1 virions, indicating that this phenomenon is
      not dependent on perturbation of the viral envelope. Nascent viral DNA synthesis
      also occurred in purified virions incubated at 37 degrees C in cell-free human
      physiological fluids including seminal plasma, blood plasma, breast milk, and
      fecal fluid. In vitro HIV-1 infection assays, in which HIV-1 DNA synthesis was
      initiated in HIV-1 virions by prior incubation with deoxyribonucleoside
      triphosphates, demonstrated that virus particles so treated had an increased
      infectious titer over untreated virions when incubated with target human T cells.
      Our data suggest that HIV-1 virion-associated DNA synthesis may occur in vivo and
      may impact on the efficiency of intra- and interhost virus transmission. If so,
      this phenomenon should prove to be an important target for antiviral therapeutic
      strategies.

PMID- 8142147
TI  - Detecting SIV gp120 and its interaction with soluble CD4 by ELISA.

PMID- 8142148
TI  - Prenatal factors may influence predisposition to breast cancer.

PMID- 8142149
TI  - Regional adoptive immunotherapy with interleukin-2 and lymphokine-activated
      killer (LAK) cells for liver metastases.
AB  - A phase lb trial of a novel regional approach to adoptive immunotherapy is
      reported. Patients with liver metastases received continuous high-dose infusion
      of interleukin-2 (IL-2) into the splenic artery or intravenous infusion with
      subsequent transfer of lymphokine-activated killer (LAK) cells into the portal
      vein or the hepatic artery. Trafficking studies revealed homogeneous distribution
      of the LAK cells within the liver. The usual side-effects of IL-2 and LAK cells
      occurred without limiting liver toxicity. One partial (7+ months) and two
      complete responses (36 and 26+ months) were observed in 9 patients with
      metastases from cutaneous melanoma. None of 6 patients with metastases from
      ocular melanoma responded.

PMID- 8142150
TI  - Treatment of relapse of breast cancer after adjuvant systemic therapy--review and
      guidelines for future research.

PMID- 8142151
TI  - Interferons combined with chemotherapy in the treatment of stage III-IV non-small
      cell lung cancer--a randomised study.
AB  - 80 patients with previously untreated stage III-IV non-small cell lung cancer
      (NSCLC) were randomly assigned to receive chemotherapy (CT) alone (arm I: 26
      patients) or the same CT combined with either interferon (IFN)-gamma (arm II: 27
      patients) or with both IFN-gamma and IFN-alpha (arm III: 27 patients). The CT
      comprised cisplatin 60 mg/m2 intravenously (i.v.) day 1 and etoposide 100 mg/m2
      i.v. days 1, 3 and 5, once every 28 days; the IFN therapy comprised either
      recombinant IFN-gamma 1b 0.2 mg/m2, subcutaneously, three times a week until day
      25, or recombinant IFN-alpha 2c 6 x 10(6) U given according to the same schedule,
      and simultaneously with IFN-gamma. A maximum of six cycles were given. The
      treatment was discontinued if progressive disease (PD) was demonstrated. The mean
      numbers of cycles per patient given in the different arms were 3.6 (arm I), 3.0
      (arm II) and 2.9 (arm III). The main reason for discontinuation in all arms was
      PD. 17 (28%) of the 61 evaluable patients achieved partial responses (35% in arm
      I, 29% in arm II and 35% in arm III, non-significant). No complete response was
      recorded. Haematological toxicity was dose-limiting in all arms: leucopenia (WHO
      grade 3) was observed universally, but more frequently in arm III (in 18% of
      cycles given). Only two episodes of grade 4 leucopenia were seen (arms II and
      III) and six episodes of grade 3-4 thrombocytopenia (arm III). Median survival
      was 6-7 months in all arms. The survival curve for arm II was slightly more
      favourable (non-significant) than those for other arms. The addition of IFN-gamma
      alone or IFN-alpha plus IFN-gamma to platinum-based CT did not improve response
      rates nor did it produce any significant survival benefit for patients with
      NSCLC. Increased haematological toxicity was observed when both IFNs were
      administered concomitantly with CT.

PMID- 8142152
TI  - Measurement and valuation of quality of life in economic appraisal of cancer
      treatment.
AB  - In the economic evaluation (EE) of technologies in cancer treatment at least
      three endpoints are relevant: costs, survival and quality of life (QoL). This
      article is focused on QoL. EE requires the use of generic and valuation QoL
      instruments at a disease non-specific level, but the inclusion of cancer-specific
      instruments may be advisable, particularly for reasons of explanation if changes
      in dimensions are small or conflicting. Given the pros and cons of the available
      questionnaires, we advocate the use of the Nottingham Health Profile, the EuroQol
      and the Rotterdam Symptom Checklist. In our experience the QoL issue in EE linked
      with cancer trials is associated with practical problems like questionnaire
      composition, follow-up time, interviewing schedule, patients' compliance and
      doctors' acceptance. These problems are discussed and some practical guidelines
      for the design of QoL measurement in cancer trials are given.

PMID- 8142153
TI  - Dose optimisation and dose intensification in malignant lymphoma.

PMID- 8142154
TI  - Spontaneous growth arrest of lung metastases of osteosarcoma with a 28-year
      follow-up. Netherlands Committee on Bone Tumours.

PMID- 8142155
TI  - Leuprolide and tamoxifen in the treatment of pancreatic cancer. A phase II study.

PMID- 8142156
TI  - NF1 gene mutation and acute myelogenous leukaemia.

PMID- 8142157
TI  - High cell proliferation activity determined by DNA flow cytometry predicts poor
      prognosis after relapse in prostate cancer.

PMID- 8142158
TI  - Intrapericardial cisplatin therapy of malignant pericardial effusions.

PMID- 8142159
TI  - Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord
      compression treated with radiotherapy: a randomised trial.
AB  - We performed a randomised single blind trial of high-dose dexamethasone as an
      adjunct to radiotherapy in patients with metastatic spinal cord compression from
      solid tumours. After stratification for primary tumour and gait function, 57
      patients were allocated randomly to treatment with either high-dose dexamethasone
      or no steroidal treatment. Dexamethasone was administered as a bolus of 96 mg
      intravenously, followed by 96 mg orally for 3 days and then tapered in 10 days. A
      successful treatment result defined as gait function after treatment was obtained
      in 81% of the patients treated with dexamethasone compared to 63% of the patients
      receiving no dexamethasone therapy. Six months after treatment, 59% of the
      patients in the dexamethasone group were still ambulatory compared to 33% in the
      no dexamethasone group. Life table analysis of patients surviving with gait
      function showed a significantly better course in patients treated with
      dexamethasone (P < 0.05). Median survival was identical in the two treatment
      groups. Similar results were found in subgroup analysis of 34 patients with
      breast cancer as the primary malignancy. Significant side-effects were reported
      in 3 (11%) of the patients receiving glucocorticoids, 2 of whom discontinued the
      treatment. We conclude that high-dose glucocorticoid therapy should be given as
      adjunct treatment in patients with metastatic epidural spinal cord compression.

PMID- 8142160
TI  - Predicting the future health care expenses of cancer.

PMID- 8142161
TI  - Screening for anxiety and depression in cancer patients: the effects of disease
      and treatment.
AB  - The General Health Questionnaire 28 (GHQ 28), Hospital Anxiety and Depression
      Scale (HADS), and Rotterdam Symptom Checklist (RSCL) seemed promising in their
      ability to detect anxiety and depression in cancer patients. To compare their
      screening performance, 513 patients were recruited from four cancer centres, and
      visited at home by a trained interviewer. Paired combinations of questionnaires
      (GHQ 28 + HADS, GHQ 28 + RSCL or RSCL+HADS) were used, and then the Psychiatric
      Assessment Schedule was administered to enable a psychiatric diagnosis to be made
      using DSM III diagnostic criteria. A receiver operating characteristics curve was
      drawn by plotting the true positive rate (sensitivity) against the false positive
      rate (1-specificity) for each possible score on each questionnaire. In the
      overall sample, the HADS and RSCL performed well comparably. The HADS did best in
      those free of disease and when the disease was judged to be stable. Only the RSCL
      performed well in those with progressive disease. Both the HADS and RSCL were
      effective in those on treatment. The GHQ was superior to the RSCL in those off
      treatment. The choice of questionnaire and threshold score should take disease
      and treatment status into account, but all three questionnaires have a definite
      role in screening out anxiety and depression.

PMID- 8142162
TI  - Non-palpable lesions of the breast detected by mammography--review of 1182
      consecutive histologically confirmed cases.
AB  - We report on 1182 consecutive histologically confirmed non-palpable breast
      lesions detected by mammography (infiltrating carcinoma 427, in situ carcinoma
      121, benign 634). The proportion of cancer cases varied according to age (< 50
      years = 33%; 50-59 years = 46%; > 59 years = 63%), mammographic pattern (regular
      opacities = 8%, parenchymal distortions = 20%, isolated calcifications = 42%,
      irregular opacities = 62%, stellate opacities = 73%), and calendar period (1970
      1985 = 29%, 1986-1989 = 56%; 1990-1992 = 69%). A sharp decrease of the
      benign/malignant biopsy ratio was evident after routine fine-needle aspiration
      cytology (sonography-guided or stereotaxic) was introduced in 1986. The
      independent significant association of cancer frequency to age, calendar period
      and mammographic pattern was confirmed by multivariate analysis. A significant
      trend over time in favour of conservative surgery was also observed for cancer
      cases (1970-1979 = 6%, 1980-1985 = 41%, 1986-1992 = 83%). Among invasive cancers,
      node involvement was observed in 11.5% of cases, being associated with tumour
      size (pT1a = 0%, pT1b = 7%, pT1c = 13%, pT2a = 33%). Five-, ten- and fifteen-year
      overall survivals of invasive cancers were 98.1, 95.7 and 87.3%, respectively.

PMID- 8142163
TI  - Phase II trial for intraperitoneal cisplatin plus intravenous sodium thiosulphate
      in advanced ovarian carcinoma patients with minimal residual disease after
      cisplatin-based chemotherapy--a phase II study of the EORTC Gynaecological Cancer
      Cooperative Group.
AB  - On the basis of its efficacy against ovarian carcinoma and its safe peritoneal
      administration, cisplatin administered by the intraperitoneal route was studied
      in a phase II multicentric trial. 34 patients with good performance status and
      residual disease less than 1 cm were treated with a 90 mg/m2 dose (60 mg/m2 at
      first cycle), administered in the abdominal cavity every 3 weeks for at least
      four cycles. In case of haematological or renal toxicity, intravenous sodium
      thiosulphate was perfused simultaneously with intraperitoneal cisplatin with
      protective intent. 25 patients were evaluable for response: 3 patients had
      pathological complete response and 1 patient had a microscopic disease (16%
      response rate in evaluable patients). Systemic toxicity was mild, and sodium
      thiosulphate clearly protected against leucopenia (6 patients) and renal toxicity
      (8 patients). Local side-effects were evaluable in 34 patients with 2 cases of
      infectious peritonitis, 1 of wound infection and 2 of haemorrhage. Of the 147
      evaluable chemotherapy cycles, nine resulted in partial and one in total inflow
      obstruction, for which 4 patients needed surgical procedures for catheter-related
      complications, and 1 patient died of acute abdominal complications after such a
      procedure. We conclude that 90 mg/m2 intraperitoneal cisplatin has activity in
      pretreated patients with minimal residual disease, and that thiosulphate protects
      against haematological and renal toxicities. Only a randomised study can
      demonstrate a true benefit, which will have to be balanced with the toxicity of
      intraperitoneal drug administration.

PMID- 8142164
TI  - Steroid receptors, pS2 and cathepsin D in early clinically node-negative breast
      cancer.
AB  - Four oestrogen-regulated proteins of reported prognostic value, oestrogen
      receptor (ER), progesterone receptor (PR), pS2 and cathepsin D (Cat D), have been
      quantified by immunoassays, and the latter studied by immunohistochemistry (IHC)
      in primary tumours from clinically node-negative early breast cancer patients,
      entered into a trial of breast conservation therapy in which all the patients
      received adjuvant tamoxifen. ER, PR and pS2 significantly co-correlated but none
      correlated with Cat D. ER, PR and pS2, but not Cat D, were significantly
      associated with tumour size and grade, although Cat D tended to show an inverse
      relationship with the latter. Cat D (radioimmunoassay) in pmol/mg significantly
      correlated with the IHC score for Cat D in carcinoma cells as well as the number
      of Cat D-expressing macrophages. At a median follow-up of only 16 months,
      recurrence was significantly more common in patients with tumours having negative
      status for ER, PR and pS2 but was not associated with Cat D status.

PMID- 8142165
TI  - Is the peak in breast cancer incidence in sight? A study conducted in the
      southeastern Netherlands.
AB  - Breast cancer is the most frequent malignancy in the western world, and increases
      in the incidence have been observed worldwide. We investigated temporal trends in
      breast cancer incidence in the southeastern Netherlands between 1960 and 1989 by
      birth cohort analysis, using data of the Eindhoven Cancer Registry. An overall
      time-trend in incidence rate was estimated, based on age and year of diagnosis.
      Rate ratios were calculated, as the ratio of the observed versus the expected
      incidence rates, which was based on the estimated time-trend. In this unscreened
      population the age-specific incidence increased for every successive birth cohort
      in the period 1880-1949. Women born between 1940 and 1949 had the highest age
      specific incidence rates with an excess of 10% (relative risk 1.10, 95%
      confidence interval 1.01-1.22). The incidence rates in women born after 1949
      declined and were 21% lower than expected by the estimated secular trend
      (relative risk 0.79, 95% confidence interval 0.64-0.96). This decrease in
      incidence for women aged under 40 suggests that the peak in incidence of female
      breast cancer may be in sight. It remains unclear which risk factors are
      responsible for this changing trend.

PMID- 8142166
TI  - Dietary risk factors for cancer and adenomas of the large intestine. A case
      control study within a screening trial in Denmark.
AB  - The aims of the study were to estimate the importance of dietary habits for
      colorectal cancers and adenomas. By comparing risk factors among cancer and
      adenoma patients the adenoma cancer theory was indirectly evaluated. The study
      was performed as a case-control study within a large screening trial in Denmark.
      All cancer and adenoma patients diagnosed at the screening were recruited as
      cases; controls were selected among test negatives after matching for age, sex
      and time of screening. All those selected except 85, participated in a 7-day
      dietary recall. Altogether 49 colorectal cancer patients and 172 with adenomas
      were examined; 362 individuals who were test negatives in the Hemoccult-II screen
      served as controls. The intake of crude dietary fibres was shown to be associated
      with reduced risk of cancer as well as adenomas. Neither cancer nor adenoma
      occurrences were related to total energy intake or body mass. Vitamins E and A
      were negatively associated with adenoma occurrence.

PMID- 8142167
TI  - Current and future costs of cancer.
AB  - Cancer costs in the Netherlands amounted to 4.8% of health care costs in 1988.
      For five cancer types, and a sixth group covering all other malignancies, costs
      were broken down by age, sex and disease phase. They showed a remarkably similar
      pattern of medical consumption. Costs were linked to observed incidence,
      mortality and estimated prevalence, together allowing for prediction of future
      costs of cancer. In 2020, as a result of ageing, cancer costs will have increased
      much more rapidly than total health care costs, in particular for cancer of the
      lung and prostate. Colorectal cancer costs were predicted for epidemiological
      scenarios. Our model shows that an increase in future prevalence may bear quite
      different cost implications. If it is due to higher incidence, the costs will
      increase substantially. If due to survival improvement, the increase will be less
      prominent. Simply extrapolating costs based on future prevalence or mortality may
      produce serious errors.

PMID- 8142168
TI  - Myofibroblast and concurrent ED-B fibronectin phenotype in human stromal cells
      cultured from non-malignant and malignant breast tissue.
AB  - Primary cultures of stromal cells from non-malignant and malignant breast tissues
      contained myofibroblasts based on immunoreactivity to alpha-smooth muscle (alpha
      sm) actin. The proportions of these cells were variable among cultures from non
      malignant origin while consistently high in cultures from carcinomas. High
      expression of ED-B fibronectin and of type V collagen was observed in
      myofibroblast-containing cultures. While cells from non-malignant tissues grew
      relatively steadily, the proliferation of carcinoma-derived cells declined during
      serial subculturing. In both types of cultures, alpha-sm actin and ED-B
      fibronectin expression decreased with increasing passage numbers. Epidermal
      growth factor (EGF), fibroblast growth factor b (FGFb), transforming growth
      factor alpha (TGF alpha) and platelet-derived growth factor (PDGF) showed
      consistent mitogenic effects. Addition of FGFb prolonged culture growth and
      allowed alpha-sm actin and ED-B fibronectin expression to persist. These results
      demonstrate similar phenotypic modulations in stromal cells from non-malignant
      and malignant breast tissues that may reflect a common stromal response to
      various tissue injuries, including neoplasia.

PMID- 8142169
TI  - Inhibition by shi-quan-da-bu-tang (TJ-48) of experimental hepatocarcinogenesis
      induced by N-nitrosomorpholine in Sprague-Dawley rats.
AB  - The effect of Shi-Quan-Da-Bu-Tang (TJ-48) on hepatocarcinogenesis induced by N
      nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were
      given drinking water containing NNM for 8 weeks, and also from the start of the
      experiment, regular chow pellets containing 2.0 or 4.0% TJ-48 until the end of
      the experiment. Preneoplastic and neoplastic lesions staining for the placental
      type of glutathione-S-transferase (GST-P) or gamma-glutamyl transpeptidase (GGT)
      were examined histochemically. In week 15, quantitative histological analysis
      showed that prolonged administration of either 2.0 or 4.0% TJ-48 in the diet
      significantly reduced the size, volume and/or number of GST-P-positive and GGT
      positive hepatic lesions. This treatment also caused a significant increase in
      the proportion of interleukin-2 receptor-positive lymphocytes among the
      lymphocytes infiltrating the tumours as well as a significant decrease in the
      labelling index of preneoplastic lesions. These findings indicate that TJ-48
      inhibits the growth of hepatic enzyme-altered lesions, and suggests that its
      effect may be in part due to activation of the immune system.

PMID- 8142170
TI  - Relation of early Photofrin uptake to photodynamically induced phototoxicity and
      changes of cell volume in different cell lines.
AB  - For efficacy of photodynamic therapy, selective uptake and retention of
      photoactive substances has been postulated. Therefore, measurements were
      performed to find out whether the photosensitiser Photofrin is taken up
      differently in malignant and non-malignant cells in vitro. In addition, the
      sensitivity of malignant cells and non-malignant cells to photodynamic exposure
      was investigated, by quantifying viability and volume alterations of the cells.
      Bovine aortic endothelial cells, mouse fibroblasts and amelanotic hamster
      melanoma cells were suspended in a specially designed incubation chamber under
      controlled conditions (e.g. pH, pO2, pCO2 and temperature). After establishing
      constant baseline conditions, the cellular fluorescence intensity per cell
      volume, indicative of the uptake of Photofrin, and cell volume were assessed by
      flow cytometry, and cell viability was quantified by the trypan blue exclusion
      test. Photodynamic exposure of cells was performed using an argon-pumped dye
      laser system via a 600 microns optical fibre at energy density of 4 Joules at the
      cell surface (40 mW/cm2, 100 s). In comparison to endothelial and fibroblast
      cells, the melanoma cells exhibited no increased uptake of Photofrin, and no
      enhanced sensitivity to photodynamic therapy (PDT). However, the fluorescence
      intensity/volume of endothelial cells was two to three times higher at each
      concentration of the photosensitiser. Following PDT, reduction in cell viability
      was dependent on the concentration of Photofrin, and directly correlated with
      fluorescence intensity per cell volume. In addition, the cells of all three
      lines, treated by PDT, revealed dose-dependent changes in cell volume. Melanoma
      cells exhibited the most excessive increase. It is suggested that selective
      uptake of photosensitiser in vitro is not characteristic for tumour cells. The
      high uptake of Photofrin by endothelial cells may indicate that the vascular
      endothelium is a major target for PDT, leading to cessation of tumour blood flow
      and subsequent destruction of tumour tissue. In addition, PDT-induced swelling of
      tumour cells might represent and effect synergistically impairing tumour
      perfusion, and thereby promoting tumour death.

PMID- 8142171
TI  - Epstein-Barr virus (EBV)-encoded membrane protein LMP1 from a nasopharyngeal
      carcinoma is non-immunogenic in a murine model system, in contrast to a B cell
      derived homologue.
AB  - Epstein-Barr virus (EBV)-encoded LMP1 gene derived from a nude mouse passaged
      nasopharyngeal carcinoma (NPC) of Chinese origin (C-LMP1) and its B cell (B95-8
      prototype)-derived counterpart (B-LMP1) were compared for their ability to induce
      tumour rejection in a mouse mammary adenocarcinoma system. Each of the two LMP1
      genes was introduced individually by retroviral vectors into a non-immunogenic
      mammary carcinoma line, S6C, that originated in an ACA (H-2f) mouse. Syngeneic
      ACA mice were immunised for 3 consecutive weeks with irradiated B- or C-LMP1
      expressors or control cells. The immunised and control mice were then challenged
      with graded numbers of viable cells from the corresponding cell line. Only the B
      LMP1 expressing cells were highly immunogenic. Up to 10(5) cells were rejected in
      pre-immunised mice, whereas at least 10(2) cells grew in non-immunised controls.
      No rejection response was detected against the C-LMP1 expressing cells which grew
      equally well in control and immunised mice, with a minimum inoculum of 10(2)
      cells in the majority of the clones. In a previous study, we found numerous
      sequence differences between B- and C-LMP1. The question of whether any of these
      differences is related to the non-immunogenicity of C-LMP1 needs further
      investigation. Meanwhile, our findings raise the possibility that the NPC cells
      may escape host rejection by the development of a non-immunogenic LMP1 variant
      under the impact of immunoselection.

PMID- 8142172
TI  - Enhanced cytotoxicity of doxorubicin encapsulated in polyisohexylcyanoacrylate
      nanospheres against multidrug-resistant tumour cells in culture.
AB  - We have studied the cytotoxicity and accumulation of doxorubicin encapsulated in
      polyisohexylcyanoacrylate nanospheres in a model of doxorubicin-resistant rat
      glioblastoma variants differing by their degree of resistance to this drug. We
      observed that the particulate form of doxorubicin was always more cytotoxic than
      free doxorubicin, whereas coadministration of drug-unloaded nanospheres with free
      doxorubicin did not modify significantly doxorubicin cytotoxicity. In C6 0.001
      cells, which were 6-fold resistant and present a pure multidrug-resistant
      phenotype, the reversal of doxorubicin resistance was complete. In C6 0.1 cells,
      which were 60-fold resistant, as with C6 1V cells (selected with vincristine),
      the reversal of doxorubicin resistance was almost complete, with a residual
      resistance factor of 2-3. In C6 0.5 cells, which were 600-fold resistant to
      doxorubicin, the reversal of resistance was only partial and, in all cases, not
      above the expected participation of P-glycoprotein to the phenotype of
      resistance. Intracellular drug accumulation after 2-h exposure to 17.2 mumol/l
      doxorubicin was systematically reduced by a factor of 2-3 when doxorubicin was
      incubated under the form of nanospheres; doxorubicin accumulation after a 2-h
      exposure to IC50 was also highly reduced in all cell lines for doxorubicin-loaded
      nanospheres. This work shows that association of doxorubicin with nanoparticles
      could provide a useful tool for circumventing multidrug resistance, probably by a
      bypass of P-glycoprotein rather than by an inhibition of this pump.

PMID- 8142173
TI  - Isolation and in vitro expansion of lymphocytes infiltrating non-small cell lung
      carcinoma: functional and molecular characterisation for their use in adoptive
      immunotherapy.
AB  - Tumour infiltrating lymphocytes (TIL) have the capability of recognising and
      lysing autologous cancer cells, both in vitro and in vivo. Advanced non-small
      cell lung carcinoma (NSCLC) is partially insensitive to chemo radiotherapy and
      has a poor prognosis: thus, for this, an immunotherapeutic approach could be
      attempted. We expanded in vitro 46 out of 70 samples of TIL derived from NSCLC.
      From proliferating TILS, a number varying from 10 to 50 x 10(9) cells was
      obtained. These lymphocytes belonged to the T cell lineage, had the capability of
      growing for 45-60 days and lysed autologous better than allogeneic cancer cells.
      In addition, analysis of the restriction maps of T cell receptor (TRC)-beta,
      demonstrated that an oligoclonal population of T cells was preselected in vivo,
      near the tumour site, and might be expanded in vivo, using phytohaemagglutin and
      interleukin 2 while maintaining the same characteristics of the original
      population. These results give a clear rationale for the use of in vitro expanded
      TIL from NSCLC in protocols of adoptive immunotherapy in patients with residual
      disease following surgery.

PMID- 8142174
TI  - [Fascination of the hand and wrist].
AB  - By 250 million years ago, the five-finger digit is established. In developmental
      terms, the human hand is both specialized and primitive. Man's hand is not a
      unique structure, it is only the way in which it is used that sets it apart from
      the other animals. Its value seems therefore to be correlated with the
      development of brain. The fact that skin and nervous system share the same
      ectoblastic origin may strengthen the symbiotic effect related to brain
      development. Since the wrist sustains and enables most of the capabilities of the
      hand, a deterioration of its function may give rise to challenging diagnostic
      problems. Therefore a classification of wrist disabilities in five main groups
      may be helpful in daily practice. An ulnar translocation, a SL-dissociation, a LT
      disruption or a carpal collapse may be clearly diagnosed. When no clear pathology
      can be demonstrated, the physician is faced with the so-called normal group. In
      those cases a ganglion or an osteonecrosis on onset may explain the pain. In any
      case however, the physician has to recall the central and physiological aspect of
      the hand, an organ which has become the symbol of man and power.

PMID- 8142175
TI  - [Post-traumatic pain in the wrist, a diagnostic challenge].
AB  - Hyperextension of the wrist may induce underestimated intrinsic and extrinsic
      ligamentous tears. Undetected scaphoid fractures show the importance of accurate
      primary diagnostic. Evaluation of the anatomic and functional integrity of the
      ligaments of the wrist remains challenging. It requires great experience, but in
      any case, radiology remains the basic diagnostic tool used by both the general
      practitioner and the specialist. Only the use of reproducible imaging techniques
      will allow for comparison between healthy and pathological side as well as for
      follow-up. Every one should master and use standardized techniques as described
      in this paper. The costs bound to appropriate imaging techniques are certainly
      lower than the consequences of misdiagnosed ligamentous damage or carpal bone
      fractures. Furthermore, standardized techniques will avoid repeating radiological
      sessions.

PMID- 8142176
TI  - [The painful wrist joint: alloplastic joint replacement].
AB  - The analysis of the etiology of the painful wrist demonstrates quite clearly an
      increasing number of "carpal collapse" as a sequence of trauma (perilunar
      dislocation), of congenital disorders and rheumatoid arthritis. The deterioration
      of the wrist joint may start locally but may end up with generalised deforming
      osteo-arthritis. In addition to traditional salvage operations (partial/total
      fusion, carpectomy) the total wrist prosthesis by Meuli (ball and socket joint)
      has its definite place in the treatment of the painful destruction and
      instability of the wrist.

PMID- 8142177
TI  - [Diagnosis, etiopathogenesis and therapy of carpal tunnel syndrome].
AB  - This is a retrospective study analyzing the operation records of 637 patients
      cured for carpal tunnel syndrome. No statistical difference could be demonstrated
      between the mean age of female compared to male. However a highly significant
      statistical difference between age distribution in between sex could be
      demonstrated (p = 0.0015). 61.3% of the female (male: 47.6%) are affected by the
      disease between 40 and 65 years and only 16.4% (male 27.6%) later on. Under 40
      years of age both sex are affected in the same proportion. This confirms that
      hormonal factors related to sex play a major role in the etiology of this disease
      affecting mainly women (71%). On the contrary, combined pathology as
      tendovaginitis, ulnaris neuropathy at the elbow, synovitis bound to rheumatoid
      arthritis and epicondylitis were equally distributed between sex.

PMID- 8142178
TI  - [Carpal instability].
AB  - Even the concept of carpal stability is not clear. The complex anatomy of the
      multiple ligaments is difficult to understand. Arthroscopy is the golden standard
      in diagnosis of ligamentary tears. But the arthroscopical findings are in
      contrast to the today's classification of carpal instability.

PMID- 8142179
TI  - [Pathophysiology of perilunate dislocation].
AB  - The anatomy of the palmar scapho-triquetral ligament was studied: on 15 hand
      specimens by means of gross anatomical dissections and MR imaging; and on a
      further 10 foetal wrist specimens, microanatomically. This ligament allows us to
      present the proximal carpal row as a socket, consisting of an upper part (the
      triquetrum, distal part of the scaphoid, and the dorsal and palmar scapho
      triquetral ligament), and a base (the concave parts of the lunatum and scaphoid,
      connected by the scapho-lunate ligament). With a hyperextension wrist injury the
      upper part follows the distal part of the carpus, while the base remains fixed at
      the radius. The upper part slips away from the base, consequently, injuring the
      ligamentous structure, or causing a scaphoid fracture. The luno-triquetral and
      the palmar scapho-triquetral ligaments are also frequently torn. The overall
      prognosis depends on the grade of ligament damage. The arthroscopy allows us to
      estimate the state of the ligament structures, therefore, it is indicated before
      any reconstructive operation.

PMID- 8142180
TI  - [Treatment of epicondylitis radialis and ulnaris humeri in tennis players with
      fraction bandage. Results of a field study].
AB  - Elbow bandages were tested at the Orthopaedic University Clinics Munster
      (Germany) and Zurich (Switzerland), as well as at the surgery of an established
      orthopaedic surgeon. Both the effect of the bandage, i.e. the soothing and de
      swelling effect, the function improvement, therapy progress and success were
      monitored and evaluated. The rest was designed as a short-term study with
      standardised scoring. After the falsification principle, the therapeutic effect
      was confirmed if a positive effect was shown during this time interval. Twenty
      six patients between the age 26 and 65 were tested, 16 males and 10 females. In
      18 cases the right arm was treated and in 8 cases the left arm. 17 cases of
      epicondylitis radialis humeri and 5 cases of epicondylitis ulnaris humeri were
      found. The time of observation was 2 weeks. The bandage effect was examined after
      7 and 14 days.

PMID- 8142181
TI  - [Does the thoracic outlet syndrome exist?].
AB  - We reviewed fourteen patients suffering from thoracic outlet syndrome (TOS). This
      allowed a critical analysis of the diagnostic tools, especially the Adson and
      Allen tests, currently used. The value of arthrography and phlebography are
      discussed in relation to the supposed pathophysiology of the disease. The
      decision to operate on those patients has to be considered in relation to the
      possible mishaps related to the surgical procedure. Particular attention has to
      be paid to post-operative perineural fibrosis, a possible cause of definite
      disability. The psychological components seem to remain mostly underestimated, a
      fact that has to be stressed and which we were able to demonstrate in our small
      sample. However, pre-operative evaluation remains difficult. No definite
      objective sign enables the surgeon to assert the presence of a thoracic outlet
      syndrome. Therefore not only the decision making but also the analysis of the
      results remains debatable. In all cases, even in the presence of clear narrowing
      of the vessels, indication to operation should be restrictive.

PMID- 8142182
TI  - [Pain--psychological or physical].
AB  - The phenomenon of pain has four dimensions: somatic, psyche, social, cultural.
      This explains the potential difficulties of the therapeutical approach, which
      remains challenging especially with long standing patients. A global
      multidisciplinary therapy seems mandatory to enable any healing or, at least, a
      significant improvement of the quality of life. The analysis of four case
      histories shows the bio-psycho-socio-cultural components of pains. This gives the
      opportunity to consider the myth of Asklepios in relation to our present culture
      and to point out some practical advice.

PMID- 8142183
TI  - [The insurance physician as partner].
AB  - Health is a social term. The insurance company physician is interconnected
      between medicine and law. His task is not only the patient's treatment but also
      responsibility to the general public. Reasons for increasing health expenses are
      discussed.

PMID- 8142184
TI  - Patent foramen ovale in adult life.

PMID- 8142185
TI  - Coronary heart disease, the menopause, and hormone replacement therapy.

PMID- 8142186
TI  - Arrhythmogenic right ventricular dysplasia: the phenotypic range defined.

PMID- 8142187
TI  - Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task
      Force of the Working Group Myocardial and Pericardial Disease of the European
      Society of Cardiology and of the Scientific Council on Cardiomyopathies of the
      International Society and Federation of Cardiology.

PMID- 8142188
TI  - Secundum atrial septal defect: routine surgical treatment is not of proven
      benefit.

PMID- 8142189
TI  - Natural history of secundum atrial septal defect in adults after medical or
      surgical treatment: a historical prospective study.
AB  - OBJECTIVE: To compare outcome in patients with medically treated secundum atrial
      septal defect (ASD) first diagnosed after the age of 25 with the long-term
      outcome in a similar group of patients after surgical closure. DESIGN: A
      historical, prospective, unrandomised study. SETTING: A tertiary referral centre.
      PATIENTS: All patients with ASD followed up since 1955 who fulfilled the entry
      criteria and had reached a current age of over 45 years--that is, 34 medical and
      48 surgical patients with a mean follow up of 25 years. MAIN OUTCOME MEASURES:
      Survival, symptoms, and complications. RESULTS: There was no difference in
      survival or symptoms between the two groups and no difference in the incidence of
      new arrhythmias, stroke or other embolic phenomena, or cardiac failure. No
      patient in either group developed progressive pulmonary vascular disease.
      CONCLUSION: Outcome in adults with ASD was not improved by surgical closure.
      Because progressive pulmonary vascular disease did not develop in any of these
      patients its prevention is not a reason for advising closure of ASD in adults.

PMID- 8142190
TI  - Effects of a patent foramen ovale on arterial saturation during exercise and on
      cardiovascular responses to deep breathing, Valsalva manoeuvre, and passive tilt:
      relation to history of decompression illness in divers.
AB  - OBJECTIVE: To determine whether the presence of a patent foramen ovale could
      result in significant arterial desaturation and affect the responses of heart
      rate and blood pressure to physiological manoeuvres and to determine whether
      responses differed between those with and those without prior clinical events
      associated with a patent foramen ovale. DESIGN: Blind controlled study. SETTING:
      Teaching hospital. PATIENTS: Divers with a large patent foramen ovale shown by
      contrast echocardiography and divided into those who had neurological
      decompression illness that started within 30 minutes of surfacing (group 1),
      those who had no history of decompression illness (group 2), and age and sex
      matched control divers who had no evidence of intracardiac shunts (group 3). MAIN
      OUTCOME MEASURES: The change in percentage haemoglobin oxygen saturation during
      treadmill exercise and the response of heart rate and blood pressure to
      physiological manoeuvres. RESULTS: There were no significant differences between
      the three groups but two divers in group 1 showed clinically important
      desaturation during exercise and unusual blood pressure and heart rate responses
      to passive tilt. These divers were notable for having the greatest number of
      episodes and the most severe single episode of spinal cord decompression illness.
      CONCLUSION: A large patent foramen ovale may be associated with clinically
      significant arterial desaturation and unusual responses of heart rate and blood
      pressure in some healthy subjects.

PMID- 8142191
TI  - Assessment of changes in blood flow through the lungs and foramen ovale in the
      normal human fetus with gestational age: a prospective Doppler echocardiographic
      study.
AB  - OBJECTIVE: To measure lung blood flow and flow through the foramen ovale in the
      normal human fetus and to assess the changes in each with gestational age and the
      proportions of combined ventricular output that the respective flows represent.
      PATIENTS AND DESIGN: 38 normal fetuses (gestational age 18-37 weeks) were studied
      prospectively with Doppler echocardiography. METHODS: Echocardiographic images
      and Doppler velocity signals were obtained from the ascending aorta, main
      pulmonary artery, and ductus arteriosus from each fetus and digitised to obtain
      arterial diameters, heart rates, and velocity-time integrals. Blood flow in each
      artery was calculated as the product of heart rate, flow-velocity integral, and
      arterial cross sectional area. Blood flow through the lung was assessed as the
      difference between flow in the pulmonary artery and ductal flow; combined
      ventricular output as the sum of aortic and pulmonary artery flows; and flow
      through the foramen ovale as the difference between flows through the aorta and
      lungs. RESULTS: Blood flow through the lungs increased exponentially with
      gestational age (r = 0.89, p < 0.001), by almost four-fold over the period of
      gestation studied, and was a mean (SD) of 22% (7%) of combined ventricular
      output. Blood flow through the foramen ovale increased exponentially by threefold
      (r = 0.77, p < 0.001), representing between 17% and 31% of combined ventricular
      output. CONCLUSIONS: Blood flow through the lungs and across the foramen ovale
      can be calculated non-invasively in the normal human fetus. Both flows increase
      exponentially with age and comprise between one fifth and one quarter of the
      combined ventricular output, proportions that remain unchanged through the second
      and third trimesters of pregnancy.

PMID- 8142192
TI  - Ten year mortality in relation to original size of myocardial infarct: results
      from the Gothenburg metoprolol study.
AB  - OBJECTIVE: To describe the relation between the extent of a myocardial infarct,
      measured according to maximum serum enzyme activity of lactate dehydrogenase, and
      mortality at 10 years. PATIENTS: In 759 patients with acute myocardial infarction
      in whom serum activity of heat stable lactate dehydrogenase had been determined
      every 12 hours for 108 hours after randomisation in an early intervention trial
      with metoprolol. MAIN OUTCOME MEASURE: Mortality at 10 years in relation to
      quartile of maximum serum lactate dehydrogenase activity and history of
      cardiovascular disease. RESULTS: Among all patients mortality at 10 years was 39%
      in the lowest quartile, 51% in the second quartile, 50% in the third, and 59% in
      the fourth (p < 0.001 for relation between infarct size and 10 year mortality).
      Among patients without a history of myocardial infarction, angina pectoris,
      diabetes mellitus, or hypertension the mortality in each quartile was 29%, 32%,
      41%, and 56%, respectively (p < 0.001 for relation between infarct size and 10
      year mortality). Among patients with any of these risk indicators the association
      between the estimated infarct size and mortality at 10 years was weak (p < 0.05).
      CONCLUSION: Estimated size of a myocardial infarct and mortality over 10 years
      seem to be related but mainly in patients without a history of cardiovascular
      disease.

PMID- 8142193
TI  - Assessment of reperfusion of the infarct zone after acute myocardial infarction
      by serial cardiac troponin T measurements in serum.
AB  - BACKGROUND: The purpose of this study was to derive indices of reperfusion and
      non-reperfusion after acute myocardial infarction (AMI) from changes in serum
      concentrations of cardiac troponin T and to test the predictive value of these
      indices. METHODS: The indices were derived from a retrospective analysis of
      changes in serum troponin T concentration in 71 patients given thrombolytic
      treatment who had immediate and late angiography (group 1). These troponin T
      indices were first tested in a blinded and prospective study of 53 consecutive
      patients eligible for thrombolytic therapy (group 2). They were then used for the
      non-invasive assessment of reperfusion of AMI in 48 patients (group 3). RESULTS:
      In group 1 troponin T serum concentration curves were biphasic in patients who
      had reperfusion < or = 5.8 h after the onset of symptoms. Release of the
      cytosolic troponin T pool resulted in a peak at 14 h and ended at 38 h. The
      probability of reperfusion was > 95% when the ratio of peak cytosolic troponin T
      concentration to concentration at 38 h (PV1/38) exceeded 1.42 or the ratio of
      troponin T concentration at 14 h to that at 38 hours (14/38) exceeded 1.09. The
      probability of the presence of non-reperfused AMI was < 5% when troponin T PV1/38
      and 14/38 ratios were < 0.99 and < 0.84 respectively. These discriminatory values
      of troponin T indices correctly classified (efficiency 96%) 48 of the 53 group 2
      patients in whom immediate and late angiography were performed. When troponin T
      indices were used to classify 48 group 3 patients who were not studied by
      immediate angiography, thrombolytic therapy was deemed to have been successful in
      82% of the treated patients, with spontaneous recanalisation in 11% and 23% of
      the non-treated patients assessed by PV1/38 and 14/38 respectively. CONCLUSION:
      The PV1/38 or 14/38 ratios of serum troponin T concentration indicated the
      effectiveness of thrombolytic therapy in achieving reperfusion of AMI.

PMID- 8142194
TI  - Long-term function in the remote region after myocardial infarction: importance
      of significant coronary stenoses in the non-infarct-related artery.
AB  - BACKGROUND: Left ventricular (LV) function is the most important determinant of
      outcome after a myocardial infarction. Global LV function after a myocardial
      infarction is affected not only by wall motion in the infarct zone but also by
      regional function in the contralateral territory. It was hypothesised that the
      presence of significant stenoses in coronary arteries supplying the contralateral
      territory might influence the ability of this region to compensate for damaged
      myocardium after a myocardial infarction. METHODS AND RESULTS: 79 patients
      treated with thrombolysis for acute myocardial infarction had coronary and
      ventricular angiograms within 24 h and at a mean follow up of 12 months after
      myocardial infarction. Wall motion in the contralateral territory was analysed
      and scored by the centre line method and the change over time was correlated with
      the presence or absence of significant (> 70%) diameter stenoses in the non
      infarct-related artery. Mean (SD) contralateral territory motion worsened, from
      0.74 (1.78) to -1.55 (2.06) SD chord (p < 0.001) in 40 patients with stenoses,
      whereas contralateral territory motion improved from -0.02 (2.4) to 0.63 (2.21)
      SD chord (p < 0.05) in the 39 patients without coronary stenoses. The same
      pattern was present whether or not the infarct artery was patent. The global left
      ventricular ejection fraction at 12 months was also related to contralateral
      territory motion (r = 0.71, p < 0.001) and to the presence of coronary stenoses
      (54 (15)% in those with coronary stenoses and 62 (16)% in those without, p <
      0.05). CONCLUSION: The results demonstrate that significant stenoses in arteries
      supplying the non-infarct territory adversely affect global and regional left
      ventricular function after a transmural infarction. Non-infarct artery anatomy
      should be considered in intervention strategies to improve left ventricular
      function after acute myocardial infarction.

PMID- 8142195
TI  - Verapamil treatment after coronary angioplasty in patients at high risk of
      recurrent stenosis.
AB  - OBJECTIVE: To evaluate the efficacy of high-dose verapamil treatment (240 mg
      twice daily) in the prevention of angiographic restenosis after primary
      successful coronary angioplasty in patients at high risk of recurrent
      obstruction. DESIGN: A placebo controlled, double blind trial in which patients
      with stable angina pectoris and patients with unstable angina or non-Q wave
      infarction treated with 330 mg aspirin and 75 mg dipyridamole twice daily were
      randomised to a verapamil group or a control group. Follow up angiography was
      performed 6 months after angioplasty or sooner if signs of recurrent ischaemia
      developed. SETTING: University department of cardiology. PATIENTS: 196
      consecutive patients undergoing coronary angioplasty from the beginning of April
      1987 to the end of March 1989 and meeting the selection criteria that included
      the presence of at least one of six predefined risk factors for restenosis. At
      the time of coronary angioplasty 113 patients had unstable angina or non-Q wave
      infarction and 83 had stable angina pectoris. RESULTS: In 89 (91%) patients in
      the verapamil group and in 83 (85%) control patients follow up angiograms were
      available. The restenosis rate was lower in the verapamil group (48.3%) than in
      the placebo group (62.7%) (odds ratio 0.56, 95% confidence interval (CI) 0.303 to
      1.025 p = 0.059). Of the 172 patients in whom follow up angiograms were
      available, 24 (13 taking verapamil and 11 taking placebo) did not comply with the
      trial for more than 40 (34) days (mean (1 SD)). For the remaining 148 patients
      the restenosis rate was 47.4% in the verapamil group and 63.9% in the placebo
      group (odds ratio 0.52, 95% CI 0.271 to 0.993, p = 0.046). In the 97 patients
      with unstable angina or non-Q wave infarction the restenosis rate was not
      significantly influenced by verapamil (55.8% with verapamil v 62.2% with placebo,
      odds ratio 0.77, 95% CI 0.339 to 1.728, p = 0.520). In the 75 patients with
      stable angina pectoris the restenosis rate dropped from 63.2% with placebo to
      37.8% with verapamil (odds ratio 0.36, 95% CI 0.137 to 0.917, p = 0.038).
      CONCLUSION: The observed beneficial effect of high-dose verapamil treatment on
      the angiographic restenosis rate in patients with stable angina pectoris and at
      increased risk of recurrent obstruction requires confirmation in further
      prospective studies.

PMID- 8142196
TI  - Cardiac neuropeptide Y and noradrenaline balance in patients with congestive
      heart failure.
AB  - OBJECTIVE: To measure plasma concentrations of noradrenaline and neuropeptide Y
      like immunoreactivity in relation to cardiac function in patients with congestive
      heart failure. DESIGN: Retrospective analysis of plasma noradrenaline
      concentrations and neuropeptide Y-like immunoreactivity in the arterial and
      coronary circulations, in patients with a high or low ejection fraction (31.3%
      (1.3%) or 17.7% (1.1%) respectively) and in healthy volunteers. SETTING:
      Cardiology department of a university hospital. PATIENTS: 41 patients with
      congestive heart failure with various aetiologies. Ten healthy volunteers served
      as a reference group. MAIN OUTCOME MEASURES: Concentrations of noradrenaline
      measured by high performance liquid chromatography and of neuropeptide Y-like
      immunoreactivity measured by radioimmunoassay. Cardiac index, pulmonary capillary
      wedge pressure, pulmonary vascular resistance, and systemic vascular resistance
      were derived by catheterisation of the right heart. Ejection fraction was
      measured by radionuclide angiography, cineangiography, or M mode
      echocardiography. RESULTS: There were pronounced and significant increases in
      circulating arterial concentrations of neuropeptide Y-like immunoreactivity and
      noradrenaline in both the high and low ejection fraction groups compared with the
      healthy subjects. In the patients myocardial release of neuropeptide Y-like
      immunoreactivity tended to be greater compared with normal subjects, but not
      significantly so. While normal subjects showed myocardial noradrenaline uptake,
      patients with congestive heart failure showed significant and progressive
      myocardial noradrenaline release. Arterial as well as coronary sinus
      concentrations of neuropeptide Y-like immunoreactivity correlated significantly
      with plasma noradrenaline concentrations from the respective sites. Plasma
      noradrenaline concentrations in the artery and coronary sinus were negatively
      correlated with ejection fraction and cardiac index; no such relations were found
      for concentrations of neuropeptide Y-like immunoreactivity. CONCLUSIONS: Both
      circulating concentrations of neuropeptide Y-like immunoreactivity and
      noradrenaline are significantly increased in moderate to severe forms of
      congestive heart failure. Plasma concentrations of neuropeptide Y-like
      immunoreactivity correlated with plasma noradrenaline concentrations, but plasma
      noradrenaline concentrations alone correlated with ejection fraction and cardiac
      index. Thus plasma noradrenaline concentration seems to be a more sensitive index
      of cardiac dysfunction than the concentration of neuropeptide Y-like
      immunoreactivity in congestive heart failure.

PMID- 8142197
TI  - QT interval dispersion in chronic heart failure and left ventricular hypertrophy:
      relation to autonomic nervous system and Holter tape abnormalities.
AB  - OBJECTIVE: To study QT dispersion in left ventricular hypertrophy and chronic
      heart failure and to determine the relation to ventricular arrhythmias. SETTING:
      Investigational laboratory of a tertiary referral centre. STUDY DESIGN: Patients
      with left ventricular hypertrophy and normal systolic function (n = 14) and
      patients with chronic heart failure (n = 18) were matched with controls (n = 17).
      The QT dispersion was examined in relation to abnormalities in resting mechanical
      and autonomic function and to the findings of 24 hour Holter monitoring. MAIN
      OUTCOME MEASURES: QT dispersion is the difference between the maximum and the
      minimum QT values from the 12 lead electrocardiogram. Mean(SD) QT dispersion from
      the 10 lead electrocardiogram was also examined once the 12 lead minimum and
      maximum values had been removed. The QT distribution is the curve describing the
      distance from the mean for all QT intervals (ms). RESULTS: All measures of QT
      dispersion were increased significantly in left ventricular hypertrophy and
      tended to increase in those with heart failure. The QT distribution was abnormal
      in both heart failure and left ventricular hypertrophy. There was no relation
      between the degree of change in QT dispersion and the incidence of ventricular
      arrhythmia on 24 hour Holter monitoring. Also there was no relation between QT
      dispersion and autonomic or mechanical abnormalities. The QT dispersion was
      related to QRS duration. CONCLUSION: Though QT dispersion and distribution are
      abnormal in left ventricular hypertrophy these findings do not support the
      hypothesis that QT dispersion reflects arrhythmic risk in either hypertrophy or
      heart failure.

PMID- 8142198
TI  - Permanent pacing for cardioinhibitory malignant vasovagal syndrome.
AB  - OBJECTIVE: To evaluate the effect of permanent pacing in cardioinhibitory
      malignant vasovagal syndrome. PATIENTS AND METHODS: 37 patients with permanent
      pacemakers for cardioinhibitory malignant vasovagal syndrome. All presented with
      syncope (median six episodes, median frequency two episodes a year) and after
      conventional investigation and invasive electrophysiological assessment they
      remained undiagnosed, and without a generally accepted indication for pacemaker
      implantation. In all vasovagal syncope with cardioinhibition (heart rate at
      syncope < 60 beats/min) developed during tilt tests performed according to the
      Westminster protocol (head up tilt at 60 degrees with a footplate support for 45
      minutes or until syncope intervenes). Dual chamber pacemakers were implanted in
      35 (95%) and VVI pacemakers in the remaining two (5%). RESULTS: Over a mean (SD)
      follow up since implantation of 50.2 (23.9) months symptomatic improvement
      occurred in 89%: 62% remained free of syncope and 27% were completely symptom
      free. The collective syncopal burden of these 37 patients was reduced from 136 to
      11 episodes each year. During follow up three patients died from unrelated
      causes. Patients who become asystolic during the tilt test (sinus pause of at
      least four seconds) experienced no greater benefit from pacing than those with
      less extreme cardioinhibition. Patients who remained free of syncope since
      implantation were younger than those who continued to experience syncope.
      Patients who remained completely symptom free after implantation were younger,
      more likely to be male, and had had fewer syncopal episodes before implantation
      than those who continued to experience syncope or presyncope. No other
      demographic, clinical, investigative, or pacing variable suggested a more
      favourable outcome after implant. CONCLUSIONS: This retrospective and
      uncontrolled experience suggests a possible role for permanent pacing in selected
      patients with cardioinhibitory malignant vasovagal syndrome. Improved acquisition
      of tilt test data may enable better selection of patients who are suitable for
      permanent pacing. A randomised prospective study to compare permanent pacing with
      no treatment or with medical treatment in cardioinhibitory malignant vasovagal
      syndrome is indicated.

PMID- 8142199
TI  - Effect of inhaled nitric oxide on raised pulmonary vascular resistance in
      children with congenital heart disease.
AB  - OBJECTIVE: To study the short-term effects of inhaled nitric oxide in infants and
      young children with congenital heart disease. SETTING: A supraregional referral
      centre for children with congenital heart disease. PATIENTS AND METHODS: 22
      infants and children aged 3-32 months (median age 5 months) with congenital heart
      disease undergoing preoperative cardiac catheterisation. All but one infant had
      intracardiac shunt lesions and 13 had increased pulmonary vascular resistance.
      During catheterisation the patients inhaled nitric oxide in a concentration of 40
      parts per million in room air. Pulmonary and systemic haemodynamic variables were
      evaluated by means of measured oxygen consumption and the Fick principle before
      and after 10 minutes' exposure to nitric oxide. RESULTS: Inhaled nitric oxide did
      not affect the systemic circulation. There was a significant reduction in the
      pulmonary vascular resistance, but only in the 13 infants with pulmonary
      hypertension, in whom pulmonary vascular resistance was reduced by 34% from 8.6
      (4.6) mm Hg.min.m2.l-1 (mean (SD)) to 5.7 (3.5) mm Hg.min.m2.l-1. The pulmonary
      circulation in infants with normal pulmonary vascular resistance was not
      affected. No statistically significant increase in methaemoglobin was seen,
      though there were large individual differences. No other side effects were seen.
      CONCLUSION: The present study shows that in infants with congenital heart disease
      inhaled nitric oxide reduced pathologically increased pulmonary vascular
      resistance without affecting systemic circulation and without important side
      effects with brief exposure.

PMID- 8142200
TI  - Cardiac abnormalities in young women with anorexia nervosa.
AB  - OBJECTIVE: To identify the characteristics of cardiac involvement in the self
      induced starvation phase of anorexia nervosa. METHODS: Doppler echocardiographic
      indices of left ventricular geometry, function, and filling were examined in 21
      white women (mean (SD) 22 (5) years) with anorexia nervosa according to the
      DSMIII (Diagnostic and Statistical Manual of Mental Disorders) criteria, 19 women
      (23 (2) years) of normal weight, and 22 constitutionally thin women (21 (4)
      years) with body mass index < 20. RESULTS: 13 patients (62%) had abnormalities of
      mitral valve motion compared with one normal weight woman and two thin women (p <
      0.001) v both control groups). Left ventricular chamber dimension and mass were
      significantly less in women with anorexia nervosa than in either the women of
      normal weight or the thin women, even after standardisation for body size or
      after controlling for blood pressure. There were no substantial changes in left
      ventricular shape. Midwall shortening as a percentage of the values predicted
      from end systolic stress was significantly lower in the starving patients than in
      women of normal weight: when endocardial shortening was used as the index this
      difference was overestimated. The cardiac index was also significantly reduced in
      anorexia nervosa because of a low stroke index and heart rate. The total
      peripheral resistance was significantly higher in starving patients than in both
      control groups. The left atrial dimension was significantly smaller in anorexia
      than in the women of normal weight and the thin women, independently of body
      size. The transmitral flow velocity E/A ratio was significantly higher in
      anorexia than in both the control groups because of the reduction of peak
      velocity A. When data from all three groups were pooled the flow velocity E/A
      ratio was inversely related to left atrial dimension (r = -0.43, p < 0.0001) and
      cardiac output (r = -0.64, p < 0.0001) independently of body size. CONCLUSIONS:
      Anorexia nervosa caused demonstrable abnormalities of mitral valve motion and
      reduced left ventricular mass and filling associated with systolic dysfunction.

PMID- 8142201
TI  - Insulin in ischaemic heart disease: are associations explained by triglyceride
      concentrations? The Caerphilly prospective study.
AB  - OBJECTIVE: To investigate the predictive value of fasting insulin concentrations
      for subsequent fatal or non-fatal ischaemic heart disease at five year follow up
      and to examine the associations between insulin and other indicators of risk.
      DESIGN: A prospective population study among 2512 men aged 45 to 59 at
      recruitment. SETTING: A whole population sample of men resident in Caerphilly,
      South Wales. MEASUREMENTS: At recruitment fasting blood samples were taken for
      measurement of plasma lipids and serum insulin. Men were re-examined at a five
      year follow up and ischaemic heart disease events during this period were
      assessed from hospital notes, death certificates, and electrocardiograms. MAIN
      RESULTS: Diabetic men and those men with a fasting blood glucose of > or = 8
      mmol/l were excluded from all analyses. In a univariate analysis the incidence of
      ischaemic heart disease increased with increasing concentration of fasting
      insulin, such that for men in the top 20% of the insulin distribution the odds of
      developing ischaemic heart disease were 1.87 relative to men in the bottom 20%.
      On multivariate analysis this relation disappeared on adjusting for plasma
      triglycerides, body mass index, and evidence of ischaemic heart disease at
      recruitment. CONCLUSION: In this population in South Wales there was no evidence
      that the fasting insulin concentration is an independent risk factor for
      ischaemic heart disease. The univariate association between insulin and incident
      disease was almost entirely explained by the association of both with
      triglycerides and body mass index.

PMID- 8142202
TI  - Anterior staircase manoeuvre for atrial transseptal puncture.
AB  - OBJECTIVE: Assessment of an anterior staircase modification to the standard
      atrial transseptal technique. DESIGN: Retrospective report on patients undergoing
      atrial transseptal puncture. SETTING: A regional cardiac centre. PATIENTS: A
      series of 658 patients catheterised between 1975 and 1991. RESULTS: Needle entry
      to the left atrium was obtained in 647 (98.3%) patients with needle and catheter
      entry to the left atrial cavity in 637 patients (96.8%). Sustained atrial
      arrhythmia occurred in six patients (0.9%) and pronounced bradycardia in one.
      Cardiac perforation occurred in three patients (0.5%) but did not cause cardiac
      tamponade. There were no deaths or embolic complications caused by the
      transseptal puncture. The anterior staircase manoeuvre was particularly useful in
      patients with problem septa--that is, when the septum bulged into the right
      atrial cavity, lacked a detectable limbic edge, was tough or tender, or when the
      right atrium was considerably enlarged. CONCLUSION: The anterior staircase
      technique is a useful modification to the atrial transseptal puncture technique
      because it allows repeated passage down the atrial septum without the need for
      guidewire and needle exchanges for repositioning in the superior vena cava.

PMID- 8142203
TI  - International Primary Pulmonary Hypertension Study.

PMID- 8142204
TI  - Are streptokinase antibodies clinically important?

PMID- 8142205
TI  - Intravenous pulse cyclophosphamide--a new regime for steroid-resistant minimal
      change nephrotic syndrome.
AB  - The treatment of steroid-resistant minimal change nephrotic syndrome (MCNS)
      continues to pose a therapeutic challenge. We conducted a randomised prospective
      controlled trial to evaluate the efficacy of i.v. cyclophosphamide compared with
      oral cyclophosphamide in 13 children with biopsy-proven steroid-resistant MCNS.
      All 7 patients receiving i.v. cyclophosphamide achieved remission; this was
      sustained in 4 patients, while 3 relapsed. However, even these 3 patients
      subsequently became steroid sensitive. Of the 6 patients who received oral
      cyclophosphamide, 2 dropped out, 1 responded and 3 children continued to remain
      steroid resistant. The children who received IV cyclophosphamide had more
      sustained remissions, longer periods without proteinuria and fewer significant
      side effects; this was achieved at a lower cumulative dose.

PMID- 8142206
TI  - Hemodialysis in infants and small children.
AB  - Hemodialysis in infants and small children requires specialized nursing staff,
      equipment and adequate access. The techniques, requirements and available
      equipment for this population are discussed.

PMID- 8142207
TI  - Mechanisms of proteinuria in nephrotic humans.
AB  - The glomerular capillary wall imposes a remarkably efficient barrier to the
      passage of proteins the size of albumin and larger. The development of heavy
      proteinuria signifies impairment of the function of this barrier. Because
      endogenous proteins of graded size are heterogeneous with respect to their
      molecular charge and undergo extensive tubular reabsorption, they are not useful
      for quantifying the extent of barrier dysfunction. An alternative approach is to
      determine the fractional clearance of uncharged and non-reabsorbable polymers of
      graded size. When combined with a hydrodynamic theory of solute transport through
      a heteroporous membrane, the intrinsic properties of healthy and diseased
      glomerular capillary walls can be inferred. This approach reveals the nephrotic
      range proteinuria that attends minimal change nephropathy to be associated with
      impairment of both the size- and charge-selective properties of glomerular
      capillary walls.

PMID- 8142208
TI  - The clinical course of hepatitis B virus-associated nephropathy.
AB  - Hepatitis B virus (HBV) infection is recognised as an important cause of
      nephrotic syndrome in endemic areas. This paper retrospectively examines the
      natural history and treatment of 70 patients with membranous glomerulonephritis
      and 1 with mesangiocapillary glomerulonephritis associated with HBV infection.
      Thirty-seven patients were in complete remission by the end of the study. The
      average duration of proteinuria in these patients was 30 months. The cumulative
      probability of remission was 64% at 4 years and 84% at 10 years. Three patients
      were still nephrotic after more than 90 months of follow-up and 2 others had
      reached end-stage renal failure. Remission occurred within 6 months of clearing
      the antigen (HBeAg) in the majority of cases. Steroids alone were given to 10
      patients and 2 received steroids and cyclophosphamide, with no beneficial effect.
      Three patients received interferon-alpha 2b. One cleared the HBeAg from the
      circulation and had a significant fall in proteinuria, but defaulted from follow
      up a month after completing treatment. One had a reduction of proteinuria but
      remained HBeAg positive. There was no change in the condition of the third.
      Although the majority of children eventually enter remission, there is a
      significant morbidity associated with the disease. Steroids and other
      immunosuppressive therapy are of no benefit. Interferon therapy may be useful,
      but has not been adequately assessed.

PMID- 8142209
TI  - Multicystic dysplastic kidney.
AB  - The contemporary literature helps us to analyze and assess the various clinical
      risks associated with MCDK. Clearly, MCDK is not an isolated developmental
      anomaly, and the child born with MCDK is at increased risk, but these risks are
      primarily directed towards: (1) the opposite kidney and lower urinary tract,
      where there is a significant likelihood of coexisting obstructive disease and
      reflux, and (2) the patient's family (current and future). In contrast, the risks
      to the patient caused by the MCDK (hypertension, infection, or malignant
      degeneration) actually appear to be quite low. Consequently, it no longer seems
      advisable to routinely remove MCDK in young patients for either diagnostic or
      prophylactic reasons. Nor is it obvious to what degree the MCDK itself requires
      long-term surveillance, although associated urological abnormalities will need
      follow-up and the patient requires periodic blood pressure screening. Hopefully,
      by careful analysis of the risks to the patient and family, the results of non
      operative management, and the long-term results of the Multicystic Kidney
      Registry, contemporary pediatric nephrologists, urologists and surgeons will be
      able to reassess their approach to the evaluation and clinical management of the
      patient with this condition.

PMID- 8142210
TI  - Dysfunctional voiding syndromes and vesicoureteral reflux.
AB  - Micturition disorders simulating neurogenic bladder disease have been loosely
      termed "dysfunctional voiding". No underlying neuropathy can be found. A variety
      of voiding disturbances have been identified since the early 1970s, each with its
      own characteristics and clinical relevance. We have classified voiding
      dysfunctions into mild, moderate and severe, according to their potential impact
      on the upper tracts. Bladder instability, the Hinman syndrome and the Ochoa
      syndrome are the only dysfunctional voiding syndromes that are associated with
      reflux or ureterovesical obstruction. Each syndrome is briefly described.

PMID- 8142211
TI  - An experience of renal replacement therapy in a combined neonatal and paediatric
      intensive care unit of Hong Kong.
AB  - Intensive care services are expensive. The experience of developing a combined
      paediatric and neonatal intensive care unit (ICU) in a regional hospital is
      reported with reference to the provision of renal support for the critically ill
      patients. The combined unit is staffed by a team of paediatric intensivists, each
      of whom has special interest in a subspecialty, including cardiology, respiratory
      medicine, nephrology and neonatology. In the past 7 years, renal replacement
      therapy (peritoneal dialysis and haemofiltration) was provided to 40 patients,
      with comparable mortality and complication rates to other reports. This
      arrangement has been feasible and might be more efficient than running separate
      paediatric and neonatal ICUs or combining the paediatric ICU with the adult ICU.

PMID- 8142212
TI  - Intensive care facilities for children.

PMID- 8142213
TI  - Clinical quiz. Tuberous sclerosis (Bourneville's disease)

PMID- 8142214
TI  - Multiple spasms of renal arteries following percutaneous transluminal renal
      angioplasty in children.

PMID- 8142215
TI  - Corticosteroid therapy does not prevent nephritis in Henoch-Schonlein purpura.

PMID- 8142216
TI  - Paediatric membranoproliferative glomerulonephritis is not decreasing in Turkey!

PMID- 8142217
TI  - Call for a registry of complications of immunization in nephrotic children!

PMID- 8142218
TI  - Prognostic indicators in children with IgA nephropathy--report of the Southwest
      Pediatric Nephrology Study Group.
AB  - Investigators in 13 pediatric nephrology centers reviewed clinical and
      pathological features in 218 children and adolescents with IgA nephropathy
      (IgAN), with particular emphasis on 80 patients who had follow-up periods of at
      least 4 years. Potential prognostic markers in the 80 children were compared
      between 12 (15%) who developed end-stage renal disease (ESRD) versus 68 who did
      not. The relationship between clinical and pathological features and the
      subsequent development of ESRD was examined using stepwise linear discriminant
      analysis in addition to standard univariate analysis. Seven variables were found
      to be predictive of ESRD: the presence of glomerular sclerotic changes,
      especially when this was associated with proliferation or sclerosis in 20% or
      more of the glomeruli; black race; hypertension at biopsy; proteinuria at biopsy;
      age at presentation; crescents; male sex. Using the resulting discriminant
      function, development of ESRD could be correctly predicted in 95% of the
      subjects. We conclude that ESRD is more common in American children with IgAN
      than was realized previously. Risk factors previously documented in adult studies
      have been confirmed, especially the presence of glomerular sclerosis,
      proteinuria, and hypertension.

PMID- 8142219
TI  - Differential excretion of urinary proteins in children with vesicoureteric reflux
      and reflux nephropathy.
AB  - We studied 40 children with a history of vesicoureteric reflux (VUR) without
      evidence of renal scarring, 93 children with a history of VUR and renal scarring
      and 10 children with previous urinary tract infections in whom the urinary tract
      was radiologically normal. Urine retinol-binding protein (RBP), albumin and N
      acetyl-beta-D-glucosaminidase (NAG) were measured in each child. All were free
      from infection at the time of the analysis. Urinary RBP and NAG levels were
      significantly elevated (P < 0.001) in the group of children with renal scarring.
      Elevated RBP levels were detected in 51% of children with bilateral renal
      scarring compared with 7% of children with unilateral scarring. Urine RBP
      excretion increased progressively according to the type of scarring, best
      determined by the type of scarring of the less affected kidney. In children with
      renal scarring, elevated NAG levels were seen mostly in the 65 children with
      bilateral scarring and severe reflux. Urine albumin excretion was elevated in 10
      children, 9 with bilateral scarring, all of whom had elevated RBP excretion.
      Urine protein excretion was unaffected by the presence or absence of persisting
      VUR. There was a strong negative correlation between glomerular filtration rate
      and RBP excretion (r = -0.69). We conclude that evidence of tubular dysfunction
      is common in children with bilateral renal scarring and usually precedes any
      glomerular protein leak. Tubular dysfunction may be the consequence of relative
      nephron hyperperfusion in the presence of bilateral scarring.

PMID- 8142220
TI  - Oxidative damage of red blood cells in haemolytic uraemic syndrome.
AB  - Changes in red blood cell (RBC) lipid peroxidation [measured by malonyl
      dialdehyde (MDA) concentration], glutathione (GSH) metabolism, antioxidant enzyme
      activities (catalase, superoxide dismutase, glutathione peroxidase) and
      haemoglobin (Hb) metabolites (metHb, carboxy Hb) were studied in six children
      with post-enteropathic (D+) haemolytic uraemic syndrome (HUS) and ten controls.
      The in vitro effect of hydrogen peroxide [acetylphenylhydrazine (APH) test] on
      GSH and Hb metabolism was also investigated. MDA levels were significantly higher
      and the antioxidant enzyme activities were lower in HUS patients than in the
      controls (P < 0.01). The oxidised glutathione concentration was significantly
      higher in the patients than in the control children (26.3 +/- 12.6 vs. 10.9 +/-
      1.8 nmol/g Hb. Percentage values of carboxy Hb and metHb were also higher in HUS
      (P < 0.01). Incubation of RBC with APH induced a more pronounced decrease in the
      concentration of GSH (P < 0.001) and a significant increase (P < 0.01) in the
      level of metHb and carboxy Hb in the HUS patients. This suggests that there is
      reduced RBC GSH stability in HUS. Utilisation of GSH and antioxidant enzymes
      leads to increased Hb oxidation and haemolysis. The oxidative damage may have an
      important role in the pathogenesis of haemolytic anaemia in HUS.

PMID- 8142221
TI  - Clinical outcome and follow-up of prenatal hydronephrosis.
AB  - Between 1987 and 1991, 160 hydronephrotic kidneys were diagnosed prenatally and
      confirmed postnatally in 100 infants. The aim of the study was to describe the
      natural history and management of primary hydronephrosis detected prenatally. We
      devised a new classification of obstructive uropathy outcome using
      ultrasonography and the diethylenetriamine penta-acetic acid scan. Accordingly,
      we classified the patients as having mild, moderate or severe hydronephrosis.
      Nine patients had pyeloplasties and 5 had ureteric reimplantations. We conclude
      that in most cases there is no need for immediate surgery, and that the initial
      approach to the management of congenital hydronephrosis should be conservative.
      We suggest that anti-bacterial prophylaxis be conventionally given to infants
      with vesicoureteral reflux and for the first 6 months of life to infants
      demonstrating moderate to severe newborn primary hydronephrosis.

PMID- 8142222
TI  - Urinary mineral excretion among normal Taiwanese children.
AB  - Prompted by a large population of children with renal stones seen in 20 of our
      country's teaching hospitals over the past 10 years, this study of urinary
      mineral excretion in normal children was performed. Fasting urine from 1,072
      normal Taiwanese school children and 24-h urine collections from 125 children
      separated into three age groups were analysed for calcium (Ca), phosphate,
      magnesium (Mg), uric acid, sodium (Na) and creatinine (Cr). Fasting Ca/Cr ratios
      were not different between the sexes. Ca/Cr ratios were higher in the 17- to 18
      year age group as were 24-h urinary Ca excretions. Urinary Mg/Cr ratios were
      higher in girls than boys and 24-h urinary Mg excretion was highest in the
      younger age groups. Urinary Mg excretion in Taiwanese children is 54%-86% lower
      than previously reported in Caucasian children. Both uric acid/Cr ratios and 24-h
      urinary uric acid excretion were highest in the youngest children. Urinary Na/Cr
      ratios and 24-h urinary Na excretion were higher in the two younger age groups.
      There was no correlation between 24-h urinary Ca and Na excretion.

PMID- 8142223
TI  - Immunization practices in childhood nephrotic syndrome: a survey of North
      American pediatric nephrologists.
AB  - The indications for immunizing children with minimal change nephrotic syndrome
      are a subject of some controversy, since it has been reported that immunization
      may not be effective or may serve as an immunogenic stimulus that precipitates an
      episode of relapse. To determine the current recommendations of practicing
      pediatric nephrologists, a questionnaire was sent to the members of the American
      Society of Pediatric Nephrology. Over half responded, and the results of the
      survey indicated that a consensus for approaching immunization does not exist.
      Further, little data are available to support any particular immunization
      practice. Several potential means to accumulate such data are outlined.

PMID- 8142224
TI  - Endothelin-1 in children with chronic renal failure.
AB  - Endothelin-1 (ET-1) was measured after extraction from plasma of normal adults
      (5.9 +/- 1.9 pg/ml, n = 22), normal children (7.1 +/- 1.86 pg/ml, n = 29), non
      haemodialysed children with chronic renal failure (CRF) (11.1 +/- 1.8 pg/ml), n =
      10), renal graft recipients (9.5 +/- 3.4 pg/ml, n = 37), haemodialysed children
      24 h after a haemodialysis session (20.02 +/- 10.9 pg/ml, n = 26) and
      haemodialysed children before and after a haemodialysis session (15.31 +/- 10.6
      and 13.8 +/- 8.5 respectively, n = 14). A sensitive and specific radioimmunoassay
      was used. ET-1 was significantly higher in non-haemodialysed CRF children and in
      renal graft recipients than in normal children (P < 0.001 and P < 0.01,
      respectively) and significantly higher in haemodialysed children when compared
      with normal children, non-haemodialysed CRF children and renal graft recipients
      (P < 0.001). ET-1 concentrations were similar in normal children and normal
      adults. ET-1 was inversely correlated with glomerular filtration rate in non
      haemodialysed CRF children (r = -0.39, P < 0.01) and positively correlated with
      extracellular volume in haemodialysed children (r = 0.435, P < 0.03). After
      haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied
      before and after a haemodialysis session.

PMID- 8142225
TI  - Dietary protein and growth in infants with chronic renal insufficiency: a report
      from the Southwest Pediatric Nephrology Study Group and the University of
      California, San Francisco.
AB  - This report describes growth and nutrition data from the feasibility phase of a
      clinical trial that was designed to evaluate the effect of diet protein
      modification in infants with chronic renal insufficiency (CRI). The purpose of
      the proposed trial was to compare the safety (effect on growth in length) and
      efficacy [effect on glomerular filtration rate (GFR)] of a diet with a low
      protein: energy (P:E) ratio versus a control diet in such patients. Twenty-four
      infants with GFRs less than 55 ml/min per 1.73 m2 were randomly assigned at 8
      months of age to receive either a low-protein (P:E ratio 5.6%) or control protein
      (P:E ratio 10.4%) formula, which resulted in average protein intakes of 1.4 and
      2.4 g/kg per day in the low and control groups, respectively. Overall energy
      intakes over a 10-month period of study averaged 92% +/- 12% recommended dietary
      allowance (RDA) for length in the low-protein group and 92 +/- 15% RDA in the
      control group. Weight for age standard deviation scores (SDS) were comparably low
      in both groups at the time of randomization (low-protein--2.0 +/- 1.3, control 
      1.9 +/- 1.1) and at the end of the study (low -1.9 +/- 1.2, control -1.7 +/-
      0.9). Length for age SDS at entry tended to be lower in the low-protein group but
      were not significantly different in the two groups (low -2.2 +/- 1.4 vs. control 
      1.7 +/- 1.4). However, at 18 months the low-protein group had a significantly
      lower SDS for length (-2.6 +/- 1.2 vs. -1.7 +/- 1.4).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8142226
TI  - Assessing iron status in children with chronic renal failure on erythropoietin:
      which measurements should we use?
AB  - Iron deficiency severely limits the efficacy of recombinant human erythropoietin
      (EPO). In order to determine how best to identify and monitor children at risk of
      developing iron deficiency, we serially measured several parameters of iron
      status in nine children before and during a 24-week period of EPO therapy. Serum
      ferritin was the best predictor of development of iron deficiency, five of the
      nine children developed iron deficiency, characterised by a poor haemoglobin
      response or evidence of microcytosis and hypochromia; all had a serum ferritin of
      60 micrograms/l or less at the start of EPO. Haemoglobin response was also
      related to change in mean red cell volume (MCV); a falling MCV, irrespective of
      absolute value, accompanying a poor response to EPO. Iron treatment in five
      children resulted in significant improvements in haemoglobin and iron status
      parameters. Although MCV remained low, there was a marked increase in red cell
      volume distribution width after iron, which may be of value in monitoring the
      response to iron therapy. We suggest that children with a serum ferritin of 60
      micrograms/l or less and those who develop a falling MCV during EPO treatment
      should receive high-dose oral iron supplementation before and during treatment
      with EPO.

PMID- 8142227
TI  - Causes of kidney allograft loss in a large pediatric population at a single
      center.
AB  - At our institution, 521 kidney transplants were performed in 429 children (mean
      age 8.7 +/- 5.6-years) between 1969 and 1991. Of these transplants, 408 were
      primary, 113 were retransplants, 347 were living related, 171 were cadaver, and 3
      were living nonrelated. Immunosuppression consisted of prednisone, azathioprine,
      and Minnesota antilymphocyte globulin (non-CSA) in 339 patients, total lymphoid
      irradiation in 8, and, more recently, cyclosporine (CSA) in addition in 168
      patients. Average follow-up was 8.8 +/- 6.0 years. Actuarial graft survival in
      the non-CSA versus CSA groups at 1 year was 77.0% versus 85.7%; at 5 years, 59.6%
      versus 71.9%. Of 136 non-CSA patients, causes of graft loss at 5 years included:
      chronic rejection in 55 (40.4%), acute rejection in 27 (19.9%), recurrent disease
      in 16 (11.8%), technical complications in 8 (5.9%), infectious complications in 4
      (2.9%), other causes in 5 (3.7%), and death with a functioning graft in 21
      (15.4%). Of 40 CSA patients, causes of graft loss at 5 years included: chronic
      rejection in 16 (40.0%), acute rejection in 8 (20.0%), recurrent disease in 6
      (15.0%), technical complications in 3 (7.5%), other causes in 2 (5.0%), and death
      with a functioning graft in 5 (12.5%). The causes of graft loss did not
      significantly differ in the non-CSA and CSA groups. Chronic rejection was the
      most common cause of graft loss in both groups. Research focusing on chronic
      rejection is needed to improve graft outcome in pediatric kidney transplantation.

PMID- 8142229
TI  - Current status of vaccines and immune globulins for children with renal disease.

PMID- 8142228
TI  - Triple immunosuppression with subsequent prednisolone withdrawal: 6 years'
      experience in paediatric renal allograft recipients.
AB  - Thirty-four children (< or = 15 years of age) with end-stage renal failure
      received 39 renal allografts between 1985 and 1991 and were treated with
      cyclosporin A (CyA), azathioprine and low-dose prednisolone (PNL). We aimed to
      withdraw PNL by 6 months after transplantation. Median duration of follow-up was
      2 years 4 months (range 0.1 month to 6 years 4 months). There were no deaths.
      Crude graft survival for living-related grafts (n = 9) was 100%, although only 1
      patient has been followed for > 2 years. For cadaveric grafts (n = 30), 1- and 5
      year actuarial graft survivals were 90% and 79% respectively. At 12 months
      posttransplant, the median (range) glomerular filtration rate for all patients
      was 63 (19-109) ml/min per 1.73 m2 (n = 25) and at 5 years was 48 (17-64) ml/min
      per 1.73 m2 (n = 9). Complications observed included rejection episodes which
      occurred after discontinuation of PNL. Long-term (after 12 months), 28% of
      patients remain on PNL. Hypertension was present in more than 50% of patients.
      Severe CyA nephrotoxicity was not seen. Catch-up growth as determined by the
      change (delta) in mean height standard deviation score (Ht-SDS) was noted at 1
      year [delta SDS/year = +0.60; P < 0.001 (n = 18)] and at 2 years [delta SDS/year
      = +0.27; P < 0.01 (n = 16)] in pre-pubertal patients. The median Ht-SDS at 2
      years for pre-pubertal children was -0.71 SD and growth velocity did not improve
      thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142230
TI  - Persistent isolated proximal renal tubular acidosis--a systemic disease with a
      distinct clinical entity.
AB  - We describe a 16-year-old female with persistent isolated proximal renal tubular
      acidosis, cerebral calcification, mental retardation, band keratopathy,
      cataracts, glaucoma and short stature. Severe metabolic acidosis and hypokalaemia
      were linked to an abnormally low renal threshold for bicarbonate reabsorption (8
      mmol/l). Maximal rates of urinary excretion of titratable acid and ammonium were
      normal; erythrocyte carbonic anhydrase II was normal. This rare case represents a
      systemic disease with a distinct clinical entity which may be transmitted by
      autosomal recessive inheritance.

PMID- 8142231
TI  - Congenital microcephaly and infantile nephrotic syndrome--a case report.
AB  - A 22-month-old girl with nephrotic syndrome and microcephaly is described. She
      had dysmorphic facies and psychomotor retardation. Her parents were first-degree
      relatives and one of her siblings had died with nephrotic syndrome and renal
      failure in infancy. An autosomal recessive inheritance is suggested. The
      diagnosis of this rare combination is discussed and the relevant literature is
      reviewed.

PMID- 8142232
TI  - HLA antigens in Arab children with steroid-responsive nephrotic syndrome.
AB  - Forty-eight Arab patients with steroid-responsive childhood nephrotic syndrome
      were studied for the frequency of HLA-A, -B, -C and -DR antigens. HLA-DR7 was
      significantly increased in the patient group (63% vs. 28%, P = 0.0002) confirming
      reports of a DR7 association in other ethnic groups and indicating a universal
      association with this antigen. HLA-CW6 was also significantly increased (44% vs.
      21%, P corr. = 0.042). HLA-DQW1 was significantly reduced in the patients (29%
      vs. 57%, P corr. = 0.012) as was HLA-CW4 (6% vs. 24%, P corr. = 0.042).

PMID- 8142233
TI  - Prognostic value of sonography in childhood nephrotic syndrome.
AB  - This retrospective case review of 43 children with primary nephrotic syndrome was
      designed to evaluate the relationship among renal ultrasound findings at
      presentation, subsequent corticosteroid responsiveness and histological
      diagnoses. Fifty-one percent of patients had abnormal sonograms; nephromegaly was
      present in 42% and increased renal echogenicity in 35%. There was no relationship
      between nephromegaly and either response to corticosteroids or specific
      glomerular lesions causing nephrosis. Although the presence of echogenic kidneys
      did not denote a particular type of renal disease, it was significantly more
      frequent in corticosteroid-resistant than in corticosteroid-responsive patients
      (62% vs. 18%, P < 0.05). We conclude that increased renal echogenicity at time of
      presentation is a possible indicator of corticosteroid resistance in children
      with primary nephrotic syndrome.

PMID- 8142234
TI  - Vincristine in steroid-resistant nephrotic syndrome.
AB  - The therapeutic response to vincristine was examined in seven children (aged 2-15
      years) with corticosteroid-resistant (CR) nephrotic syndrome (NS) with focal and
      segmental glomerulosclerosis (FGS). Five were also resistant to cyclophosphamide.
      Vincristine was given weekly (1.5 mg/m2 intravenously) for 8 weeks.
      Simultaneously, prednisone (60 mg/m2 per day, orally) was given for 4 weeks and
      then gradually tapered. Two of these patients had a complete and stable
      remission; in five no benefit was observed. It was not possible to identify any
      characteristics to predict the response to vincristine. Although there is a case
      for trying vincristine therapy in CR NS with FGS, the results of this study are
      not encouraging and a better understanding of its action and indications is
      necessary.

PMID- 8142235
TI  - Potter sequence and consanguinity--a case report.
AB  - The first child of first-cousin parents had Potter sequence, including
      rudimentary, dysplastic kidneys and pulmonary hypoplasia. The girl died after 5
      h. During the next pregnancy, early fetal ultrasound was normal. In the 33rd
      week, however, ultrasound revealed oligohydramniosis and reduced renal size.
      After 40 weeks of gestation a healthy girl of normal weight without any stigmata
      was born. Her pulmonary function and X-ray were normal. Renal ultrasound
      demonstrated small kidneys with high echogenicity. There was a transient renal
      insufficiency with a peak serum creatinine of 160 mumol/l. At 5 months of age the
      infant still has an increased serum creatinine concentration of 57 mumol/l and an
      inulin clearance of 29 ml/min per 1.73 m2. In this case there is a possibility of
      an autosomal recessive inheritance.

PMID- 8142236
TI  - Curvularia urinary tract infection: a case report.
AB  - A healthy 5-year-old child had recurrent symptomatic urinary tract infections,
      the last of which was accompanied by black specks in her urine. These specks were
      identified as Curvularia species, a dermatiaceous mold. Symptoms resolved and
      fungi disappeared with long-term hydration, without specific antifungal
      treatment.

PMID- 8142237
TI  - Autosomal recessive polycystic kidney disease in 15 Arab children.
AB  - The study includes 15 children (8 males, 7 females) with autosomal recessive
      polycystic kidney disease (ARPKD) whose ages at diagnosis ranged from 2 days to 7
      years (median 10 months). Eleven (73.3%) patients were hypertensive on admission
      and 1 developed hypertension 4 months later; 5 patients became normotensive after
      receiving treatment for 18-36 months (mean 23.2 months). Patients were followed
      for a period of 1-48 months (mean 20.9 months). Glomerular filtration rate
      remained normal in 7 patients, improved in 4 and deteriorated in 1. Two patients
      died soon after diagnosis and 1 was lost to follow-up and is assumed dead. Of the
      4 patients less than 6 months old at the time of diagnosis, only 1 is alive
      compared with 10 of 11 presenting after 6 months of age. The cumulative chance of
      survival from the time of diagnosis was 85% at 3 months and 77% at 6 months. The
      study highlights the reversible nature of hypertension in ARPKD. Survival is
      better in patients older than 6 months at the time of diagnosis and those
      surviving 6 months follow-up.

PMID- 8142238
TI  - Accuracy of urine output measurement with regular disposable nappies.
AB  - Evaporation of urine from four types of disposable absorbent infant nappies (A,
      B, C, D) was assessed under a radiant warmer or in an incubator, with or without
      phototherapy. Each nappy was weighed dry and then 5, 10, 15 or 30 ml of urine
      were added. The nappy was immediately reweighed, placed in its study environment
      and then weighed 5, 15, 30, 60 and 120 min later. Under all conditions, the
      percentage evaporation from each type of nappy increased during the 120 min and
      was inversely correlated with urine volume. Without phototherapy, the maximum
      evaporation at 120 min with a 5-ml urine sample was 15.9% +/- 6.1% for nappy B in
      the incubator and 20.8% +/- 4.0% for nappy A in the radiant warmer. Phototherapy
      was associated with slight but significant changes in evaporation in the
      incubator and the radiant warmer. Nappy D allowed the lowest percentage
      evaporation in the incubator with or without phototherapy and in the radiant
      warmer with phototherapy (8.8% +/- 4.4%, 2.4% +/- 1.8% and 16.0% +/- 10%,
      respectively for a 5-ml urine sample).

PMID- 8142239
TI  - Pseudotumor cerebri with vision impairment in two children with renal
      transplantation.
AB  - The syndrome of pseudotumor cerebri consists of headaches, difficulty with vision
      and papilledema associated with raised intracranial pressure (ICP) without
      localizing neurological mass lesions. Recently, an association of pseudotumor
      cerebri and renal insufficiency, chronic dialysis or renal transplantation has
      been noted. Loss of vision remains a serious threat in children with pseudotumor
      cerebri. We report two children who developed pseudotumor cerebri with impairment
      of vision 5 years after renal transplantation. An awareness of this association
      should prompt the nephrologist to investigate and treat the symptoms of raised
      ICP to prevent visual loss.

PMID- 8142240
TI  - Prompt remission of post-renal transplant nephrotic syndrome with high-dose
      cyclosporine.
AB  - A 2.8-year-old girl with focal segmental glomerulosclerosis had recurrence of
      nephrotic syndrome within 3 days of renal transplantation and the serum
      creatinine increased. Renal biopsy showed cellular rejection and also complete
      effacement of the epithelial cell foot processes. The rejection responded to
      methylprednisolone therapy but massive proteinuria persisted. An increase in the
      dose of cyclosporine A to 14 mg/kg per day was followed by immediate remission of
      the proteinuria. One month later, a second renal biopsy showed only focal fusion
      of foot processes. She remains free of proteinuria 2 years later. We propose that
      the higher dose of cyclosporine caused remission of the nephrotic syndrome.

PMID- 8142241
TI  - Continuous arterial-venous diahemofiltration and continuous veno-venous
      diahemofiltration in infants and children.
AB  - Continuous arterial-venous diahemofiltration and continuous veno-venous
      diahemofiltration [CAVH(D)/CVVH(D)] in the infant and pediatric population is
      increasingly being utilized in the child needing renal replacement therapy (RRT).
      Difficulties with infant- and pediatric-specific equipment remains a limitation.
      The availability of techniques and equipment in this unique population is
      addressed. Use of this form of RRT as opposed to hemodialysis or peritoneal
      dialysis is discussed. The decision for CAVH(D) or CVVH(D) remains an individual
      choice.

PMID- 8142242
TI  - Influenza.

PMID- 8142243
TI  - Acquired immunodeficiency syndrome (AIDS)--data as at 31 December 1993.

PMID- 8142244
TI  - The current global situation of the HIV/AIDS pandemic.

PMID- 8142246
TI  - Influenza.

PMID- 8142245
TI  - Human plague in 1992.

PMID- 8142247
TI  - Vaccination requirements. Pilgrimage to Mecca (Hajj).

PMID- 8142248
TI  - Expanded programme on immunization. Global Advisory Group--Part I.

PMID- 8142249
TI  - Expanded programme on immunization. Global Advisory Group--Part II. Achieving the
      major disease control goals.

PMID- 8142250
TI  - Outbreak of meningococcal meningitis.

PMID- 8142251
TI  - Phosphorus metabolism during growth of lymphoma in mouse liver: a comparison of
      31P magnetic resonance spectroscopy in vivo and in vitro.
AB  - Large phosphomonoester (PME) signals are detected in the phosphorus magnetic
      resonance spectra (31P MRS) of many neoplastic and rapidly dividing tissues. In
      addition, alterations in phosphodiester (PDE) signals are sometimes seen. The
      present study of a murine lymphoma growing in liver showed a positive correlation
      between the hepatic PME/PDE ratio measured in vivo by 31P MRS at 4.7 T and the
      degree of lymphomatous infiltration in the liver, quantified by histology. High
      resolution 31P MRS of liver extracts at 9.7 T showed that the PME peak consists
      largely of phosphoethanolamine (PE) and to a lesser extent of phosphocholine
      (PC). The concentration of both PE and PC increased positively with lymphomatous
      infiltration of the liver. In vivo, the PDE peak contains signals from
      phospholipids (mostly phosphatidylethanolamine and phosphatidylcholine) and the
      phospholipid breakdown products glycerophosphoethanolamine (GPE) and
      glycerophosphocholine (GPC). Low levels of GPE and GPC were detected in the
      aqueous extracts of the control and infiltrated livers; their concentrations
      remained unchanged as the infiltration increased. The total concentration of
      phospholipids measured by 31P MRS of organic extracts decreased about 3-fold as
      the infiltration increased to 70%. Thus, our data showed that the increased
      PME/PDE ratio in vivo is due to both an increase in the PME metabolites and a
      decrease in the PDE metabolites. We propose that this ratio can be used as a non
      invasive measure of the degree of lymphomatous infiltration in vivo.

PMID- 8142252
TI  - Pharmacokinetics in melanoma-bearing mice of 5-dihydroxyboryl-6-propyl-2
      thiouracil (BPTU), a candidate compound for boron neutron capture therapy.
AB  - Blood pharmacokinetics and tissue distribution of 5-dihydroxyboryl-6-propyl-2
      thiouracil (BPTU), a boron carrier with postulated melanin-seeking properties for
      boron neutron capture therapy, were determined in C57/BL mice with subcutaneous
      pigmented or non-pigmented B16 melanomas. Borocaptate sodium (BSH) was used as a
      boron compound without melanin-seeking properties in a comparative
      biodistribution study in the same animal tumour models. Administration of single
      doses showed that BPTU was retained better in the pigmented B16 tumour than in
      the non-pigmented variant. BPTU was found in large concentrations in kidney and
      liver. Brain boron was approximately 10-fold lower than tumour boron. On a molar
      basis, BPTU demonstrated higher affinity for B16 tumours than BSH. Owing to
      solubility limits, tumour boron concentrations in this mouse study were too low
      for effective application of BNCT. However, the high tumour-to-blood and tumour
      to-normal tissues ratios indicate that, with appropriate formulation, BPTU could
      be a promising candidate for clinical BNCT.

PMID- 8142253
TI  - Enhancement of cyclophosphamide cytotoxicity in vivo by the benzamide analogue
      pyrazinamide.
AB  - The ability of pyrazinamide to enhance the in vivo cytotoxicity of
      cyclophosphamide in Lewis lung and RIF-1 tumours was investigated. Using an in
      vivo/in vitro excision assay a large single dose of pyrazinamide (500 mg kg-1
      i.p.) was shown to enhance the tumour cell killing by cyclophosphamide. This
      enhancement was greatest when pyrazinamide was administered before the alkylating
      agent and had a dose-modifying effect on all cyclophosphamide doses tested,
      giving rise to a mean (+/- 1 s.e.) enhancement ratio (ER) of 1.54 (+/- 0.15) for
      the Lewis lung and 1.24 (+/- 0.08) for the RIF-1 tumour. Pyrazinamide also
      increased the cytotoxic action of cyclophosphamide in a normal tissue, namely
      white blood cell counts. However, the ER was only 1.14 (+/- 0.08), which although
      not significantly different from the value seen in RIF-1 was significantly less
      than the ER obtained with Lewis lung, suggesting the possibility of a therapeutic
      gain. This benzamide analogue did not appear to inhibit recovery from
      cyclophosphamide-induced potentially lethal damage in tumours, nor did it alter
      the bioactivation of cyclophosphamide or the subsequent clearance of the
      cytotoxic species from the plasma, so the mechanism for this chemosensitisation
      remains unclear.

PMID- 8142254
TI  - Detection of malignancy-associated metabolites in the sera of cancer patients by
      electron capture gas chromatography.
AB  - A reliable test that detects malignancy and indicates response to therapy is
      needed. Frequency-pulsed electron-capture gas-liquid chromatography (FPEC-GLC), a
      selective analytical technique that is sensitive to 15 fmol quantities of
      metabolites, was used to analyse derivatised acidic chloroform extracts of sera
      from patients with biopsy-proven cancer, non-malignant infectious and non
      infectious disease, and healthy controls. Two peaks designated P1 and P10, not
      found in serum from healthy controls (n = 7) or patients with non-malignant
      disease (n = 85), were detected in biopsy-proven samples (n = 52) from cancer
      patients. P1 and P10 were later shown by chemical and mass spectral studies to be
      carboxylic acids. When one or both of these peaks were detected in the sera of
      non-treated patients they were always associated with malignancy. In patients
      responding to therapy, a reduction or disappearance of these peaks was observed.
      Further, it was noted that P10 persisted or increased in sera of patients with
      progressive cancer not responding to therapy. We conclude that this test has
      potential in diagnosis and for following the response of the disease to therapy.

PMID- 8142255
TI  - Changes in c-myc expression and the kinetics of dexamethasone-induced programmed
      cell death (apoptosis) in human lymphoid leukaemia cells.
AB  - The kinetics of dexamethasone-induced death of CCRF CEM clone C7A human
      lymphoblastic leukaemia cells was determined with respect to changes in the
      expression of the c-myc protein. Cell death was characterised as being by
      apoptosis: cells with an intact plasma membrane had condensed chromatin and were
      characterised as having approximately 300 kbp fragments when DNA integrity was
      analysed by pulsed-field electrophoresis. Onset of apoptosis required a minimum
      of 36 h exposure to 5 microM dexamethasone; before this time no apoptotic cells
      were observed. This 36 h incubation period appeared to be necessary to prime the
      cells for subsequent death by apoptosis. In the continued presence of
      dexamethasone the percentage of apoptotic cells increased to 60% apoptotic cells
      by 54 h. Investigation of changes in c-myc protein showed that it was
      undetectable after 12 h of incubation with dexamethasone, although cells were not
      committed to die at this time. Cells were treated with dexamethasone for 54 h and
      for various pulsed periods with a non-toxic concentration of cycloheximide (200
      nM). When cycloheximide was present during the first 36 h priming period of
      dexamethasone treatment, there was an immediate loss of c-myc protein and
      apoptosis at 54 h was completely inhibited. In contrast, there was no inhibition
      of apoptosis when dexamethasone-treated cells were incubated with an 18 h pulse
      of cycloheximide added after 36 h. Cells exposed to dexamethasone for 36 h
      ('primed') were given various periods of dexamethasone-free incubation before
      readdition of dexamethasone for a further 18 h. The longer the cells were free of
      drug after priming, the less susceptible they became to apoptosis, suggesting a
      slow decay of their 'memory' of the initial 36 h period of exposure.
      Cycloheximide inhibited the decay of this memory. Removal of dexamethasone after
      a 36 h exposure was characterised by a subsequent 24 h suppression of c-myc
      protein expression. Despite this, 90% of cells became refractory to apoptosis
      before the reappearance of c-myc protein. The evidence does not support the
      hypothesis that changes in c-myc expression are required for the engagement of
      apoptosis of CEM cells.

PMID- 8142256
TI  - Altered stability of etoposide-induced topoisomerase II-DNA complexes in
      resistant human leukaemia K562 cells.
AB  - K562 leukaemia cells were selected for resistance using 0.5 microM etoposide (VP
      16). Cloned K/VP.5 cells were 30-fold resistant to growth inhibition by VP-16 and
      5- to 13-fold resistant to m-AMSA, adriamycin and mitoxantrone. K/VP.5 cells did
      not overexpress P-glycoprotein; VP-16 accumulation was similar to that in K562
      cells. VP-16-induced DNA damage was reduced in cells and nuclei from K/VP.5 cells
      compared with K562 cells. Topoisomerase II protein was reduced 3- to 7-fold and
      topoisomerase II alpha and topoisomerase II beta mRNAs were each reduced 3-fold
      in resistant cells. After drug removal, VP-16-induced DNA damage disappeared 1.7
      times more rapidly and VP-16-induced DNA-topoisomerase II adducts dissociated 1.5
      times more rapidly in K/VP.5 cells than in K562 cells. ATP (1 mM) was more
      effective in enhancing VP-16-induced DNA damage in nuclei isolated from sensitive
      cells than in nuclei from resistant cells. In addition, ATP (0.3-5 mM) stimulated
      VP-16-induced DNA-topoisomerase II adducts to a greater extent in K562 nuclei
      than in K/VP.5 nuclei. Taken together, these results indicate that resistance to
      VP-16 in a K562 subline is associated with a quantitative reduction in
      topoisomerase II protein and, in addition, a distinct qualitative alteration in
      topoisomerase II affecting the stability of drug-induced DNA-topoisomerase II
      complexes.

PMID- 8142257
TI  - Repair of O6-alkylguanines in the nuclear DNA of human lymphocytes and leukaemic
      cells: analysis at the single-cell level.
AB  - Inter-individual and cell-cell variability of repair of O6-alkylguanines (O6
      AlkGua) in nuclear DNA was studied at the single-cell level in peripheral
      lymphocytes from healthy donors and in leukaemic cells isolated from patients
      with chronic lymphatic leukaemia (CLL) or acute myeloid leukaemia (AML). Cells
      were pulse exposed to N-ethyl- or N-(n-)butyl-N-nitrosourea in vitro, and O6
      AlkGua residues in DNA were quantified using an anti-(O6-AlkGua) monoclonal
      antibody and electronically intensified fluorescence. The kinetics of O6-AlkGua
      elimination revealed considerable inter-individual differences in O6-ethylguanine
      (O6-EtGua) half-life (t1/2) values in DNA, ranging from 1.5 to 4.5 h (five AML
      patients), from 0.8 to 2.8 h (five CLL patients) and from 1.2 to 7.3 h (five
      healthy donors). The elimination from DNA of equimolar amounts of O6-butylguanine
      was generally 3-5 times slower in comparison with O6-EtGua. The t1/2 values of
      individual samples varied in parallel for both DNA alkylation products. Upon
      preincubation with O6-benzylguanine, the activity of the DNA repair protein O6
      alkylguanine-DNA alkyltransferase (AT) in both lymphocytes and leukaemic blasts
      was reduced to < or = 1%. However, while the rate of O6-EtGua elimination from
      DNA was decelerated it was not abolished, suggesting the possible involvement of
      additional repair systems that might be co-regulated with AT. Within individual
      samples, no major cell subpopulations were observed whose repair kinetics would
      differ significantly from the remaining cells.

PMID- 8142258
TI  - The effect of cryotherapy on the cremaster muscle microcirculation in vivo.
AB  - The effect of cryotherapy on normal striated muscle was investigated using 18
      adult male rats. Animals were divided into two groups, an experimental
      cryotherapy group and a control group receiving sham treatment. After the
      surgical procedure animals were allowed to equilibrate and vessel diameters,
      macromolecular leakage and blood flow were assessed before the cremaster muscle
      was frozen to -60 degrees C. After thawing measurements were taken every 15 min
      over a 2 h period. Cryotherapy resulted in an initial reduction in blood flow
      followed by a brief period of reperfusion, with complete vascular stasis
      eventually observed. Macromolecular leakage occurred from all vessels, which
      mirrored the fluctuations in blood flow. Transient changes in vessel diameters
      were also observed. Histology confirmed the in vivo observations of vessel
      congestion and muscle damage. The data suggest that cessation of flow and
      increased macromolecular leakage within the muscle may contribute to the cell
      death and tumour necrosis observed following cryotherapy.

PMID- 8142259
TI  - Prospective evaluation of cell kinetics in head and neck squamous carcinoma: the
      relationship to tumour factors and survival.
AB  - Tumour growth rates were measured in 105 patients using in vivo incorporation of
      bromodeoxyuridine (BrdU) and investigated for any relationship to tumour factors
      or survival. The median labelling index (LI) was 8.7%, the duration of S-phase
      (Ts) was 14 h and the potential doubling time (Tpot) was 5.9 days. The labelling
      index in aneuploid tumours was significantly higher than that in diploid tumours.
      However the total labelling index (TLI) did not differ significantly between
      aneuploid and diploid tumours, and so it would seem likely that the difference in
      LI is due to the dilutional effect of benign tissue upon the calculation of LI in
      diploid tumours. The total labelling index, duration of S-phase and potential
      doubling time were not related to the tumour factors examined (site, T stage, N
      stage, stage grouping). Interim survival analysis was carried out and there was
      no difference in survival between those patients with high values for TLI, Ts,
      and Tpot and those with low values.

PMID- 8142260
TI  - Serum CA549 in primary breast cancer: comparison with CA15.3 and MCA.
AB  - We carried out a comparison of three commonly used mucin markers, CA549, CA15.3
      and MCA. Serum samples from 184 healthy women and 237 patients with primary
      breast cancer were evaluated. The markers were measured using commercially
      available immunometric assays. Like CA15.3 and MCA, CA549 was significantly
      associated with tumour size and lymph node status, being an effective indicator
      of tumour bulk. CA549 was significantly correlated with both CA15.3 and MCA.
      Positive/negative concordance rate was very good (93.7%) between CA549 and MCA.
      Conversely, CA15.3 was positive and CA549 negative in 20.4% of cases. Axillary
      status was not significantly different in the latter group of patients and in
      cases in which CA15.3 and CA549 showed concordant results. From the present
      findings we draw the following major conclusions: 1. CA549 and MCA are highly
      correlated and their association should not provide additional information;
      however, they should not be considered interchangeable since they may behave
      differently in individual cases. 2. CA549 and CA15.3, although well correlated,
      are discordant in a significant number of cases. Longitudinal studies are needed
      to verify the usefulness of the association between the two markers. 3. The three
      evaluated mucin markers are not interchangeable in individual patients; if a
      patient is monitored with a marker, she should be followed up with the same
      marker.

PMID- 8142261
TI  - Iododoxorubicin in advanced breast cancer: a phase II evaluation of clinical
      activity, pharmacology and quality of life.
AB  - Iododoxorubicin 80 mg m-2 i.v. was given 3 weekly for a maximum of six cycles as
      first-line chemotherapy to 14 evaluable women with metastatic breast cancer. The
      response rate was 14% (95% confidence intervals 4-40%); median time to
      progression was 3.5 months (range 0.7 to > 9.3) and median survival was 10.2
      months (range 2.3 to > 20.4). Neutropenia was the main toxicity but was not
      associated with severe sepsis. Two patients had a significant (> 10%) but
      asymptomatic fall in cardiac ejection fraction; other toxicities were mild.
      Plasma pharmacokinetics was studied during the first cycle of treatment.
      Iododoxorubicin was extensively metabolised to iododoxorubicinol. Neutropenia and
      thrombocytopenia were both significantly correlated with the area under the
      concentration-time curve (AUC) for iododoxorubicin and the total AUC for
      iododoxorubicin and iododoxorubicinol. Quality of life (QOL), evaluated by self
      report questionnaire and interview, showed little evidence of benefit in terms of
      physical symptom relief, level of activity, psychological symptoms or global
      evaluation of QOL during treatment. Iododoxorubicin is subjectively less toxic
      than standard anthracyclines, but at the dose and schedule used has limited
      activity in metastatic breast cancer, possibly because iododoxorubicinol is not
      clinically active.

PMID- 8142262
TI  - p53 mutations in cervical carcinogenesis--low frequency and lack of correlation
      with human papillomavirus status.
AB  - p53 gene aberrations are common in human malignancies, and recent studies suggest
      that in cervical carcinoma p53 function is inactivated either by complex
      formation with human papillomavirus (HPV) E6 product or by gene mutation. Using
      polymerase chain reaction (PCR) followed by denaturing gradient gel
      electrophoresis (DGGE), we examined the mutational status of the four 'hotspot'
      regions of the p53 gene in 47 primary cervical carcinomas. HPV status was
      determined, also by PCR. In 20 of these cases, we examined for loss of
      heterozygosity (LOH) on chromosome 17p13. In the 47 carcinomas, and in a further
      68 biopsy specimens from normal, premalignant and malignant cervix, we
      investigated aberrant immunocytochemical expression of p53. Immunocytochemically,
      abnormal p53 expression was detected in 13 of 115 cases (8/57 carcinomas).
      Somatic mutation in p53 was detected in 1 of 47 cervical carcinomas; 36 were
      positive for HPV 16, 18 or 33. A low level of allele loss (3 out of 20 cases) was
      detected on chromosome 17p, occurring in both HPV-positive and HPV-negative
      cases, and in cases with and without p53 mutations. We conclude that somatic
      mutation in the hotspot regions of the p53 gene occurs infrequently in cervical
      carcinomas; that immunocytochemically detectable levels of p53 are also
      infrequent; and that there is no consistent correlation between p53 mutational
      status, LOH on chromosome 17p or HPV status in these cancers.

PMID- 8142263
TI  - Protein kinase A (PK-A) regulatory subunit expression in colorectal cancer and
      related mucosa.
AB  - Photoaffinity labelling (PAL) with [32P]8-azido-cAMP and polyacrylamide gel
      electrophoresis (PAGE) has been used to identify three specific cAMP-binding
      proteins (cAMP-BPs) within cytosols derived from the centre and periphery of 32
      human colorectal cancers and from related adjacent (less than 5 cm from the
      tumour) and distant (more than 5 cm from the tumour) microscopically benign
      mucosa. By immunoprecipitation with specific anti-RI and anti-RII antibodies
      these proteins have subsequently been characterised as a single form of RI (48
      kDa) and two forms of RII (50 and 52 kDa). The relative expression of isoforms in
      each specimen has been quantified by laser densitometry. There was significantly
      more RI expressed in both tumour centre and periphery than in either adjacent or
      distant mucosa (P < 0.008 by Wilcoxon signed-rank test). There was no significant
      difference in relative RI expression between tumour centre and periphery, or
      between adjacent and distant mucosa. There was no association between relative RI
      expression and Dukes' stage. Poorly differentiated tumours expressed
      significantly more RI than those that were either moderately or well
      differentiated (P = 0.016 by Mann-Whitney U-test). This study is the first to
      have characterised cAMP-BPs within human colorectal tissues and has demonstrated
      that colorectal cancers, and in particular those of poor histological grade,
      relatively overexpress RI when compared with related benign mucosa.

PMID- 8142264
TI  - A 27 kDa heat shock protein that has anomalous prognostic powers in early and
      advanced breast cancer.
AB  - This paper describes a prospective immunohistochemical analysis of 27 kDa heat
      shock protein (HSP27) in 361 patients with primary breast cancer in relation to
      disease-free survival (DFS) and survival from first relapse (SR). Oestradiol (ER)
      and progesterone (PR) receptors were also quantitated and related to the HSP27
      data. While ER positively predicted a good outcome for both DFS and SR, HSP27
      positivity predicted a prolonged SR but short DFS. The association between HSP27
      and DFS only attained statistical significance in node-negative patients.
      Subgroup analysis reinforced the complementary relationship of HSP27 and ER for
      SR and opposing influences for DFS. In both node-negative and node-positive
      women, ER+ HSP27- patients had a longer DFS than ER- HSP27+ counterparts. There
      was no relationship between HSP27 and overall survival. HSP27 staining was highly
      correlated with ER but not PR, patient age, tumour size or menstrual status.
      There was a marginal correlation (P = 0.04) with histological grade with well
      differentiated tumours having the highest HSP27. Cox multivariate regression
      analysis of the contribution of HSP27 in the presence of data on ER, PR, stage,
      nodal status and histological grade indicated that HSP27 was not of independent
      prognostic importance for DFS or overall survival and was only of borderline
      significance for OS (P < 0.07). However, in the absence of ER and PR data, HSP27
      staining is an effective way of getting the same prognostic information. HSP27
      staining appears to correlate with different biological features in early and
      advanced breast, high HSP27 being linked with short DFS in node-negative patients
      but with prolonged survival from first recurrence.

PMID- 8142265
TI  - Positive effect of tamoxifen as part of adjuvant chemo-endocrine therapy for
      breast cancer. Hokkaido Adjuvant Chemo-Endocrine Therapy for Breast Cancer Study
      Group.
AB  - A prospective randomised multicentre clinical study was undertaken for 2 years
      and 3 months from November 1982, with the aim of examining the significance of
      using a combination of ftorafur (FT) and tamoxifen (TAM) for post-operative
      adjuvant therapy of breast cancer. Patients had either stage II or stage IIIa
      disease, were age 75 or below and had undergone radical mastectomy. Patients were
      divided into two groups and received one of the following treatment protocols:
      treatment A, intravenous administration of doxorubicin (DOX), 20 mg on the day of
      surgery and 10 mg the next day, followed by oral FT 50 mg day-1 for 2 years from
      the 14th day; treatment B, the same pattern of DOX administration for the first 2
      days, followed by a combined therapy of FT and TAM 20 mg day-1 for 2 years. The
      number of patients was 546 (treatment A 274 and treatment B 272), of whom 34 (6%)
      were ineligible. The remaining 512 patients (treatment A 254 and treatment B 258)
      were followed up for 5 years for analysis. Significantly higher 5 year disease
      free rate and 5 year survival rates were observed with treatment B compared with
      treatment A. When seen in terms of background factors, node-positive patients
      appeared to derive more benefit from tamoxifen than node-negative patients, but
      the oestrogen receptor-negative and premenopausal subgroups appeared to derive
      about the same benefit as those who were oestrogen receptor positive and post
      menopausal. Indeed, survival in the premenopausal group was significantly better
      with tamoxifen (P = 0.04). No increase in side-effects was seen by combining TAM
      with FT. The study results demonstrate that concomitant administration of FT and
      TAM is better than FT alone for post-operative adjuvant therapy for breast
      cancer.

PMID- 8142266
TI  - Transforming growth factor beta 1 secreted from scirrhous gastric cancer cells is
      associated with excess collagen deposition in the tissue.
AB  - To explore the mechanism of increased collagen deposition in scirrhous carcinoma
      of the stomach, an attempt was made to define the role of transforming growth
      factor beta 1 (TGF-beta 1), secreted from tumour cells, as a possible humoral
      factor which functions in a paracrine manner to stimulate the production of
      collagen in regional fibroblasts. Immunohistochemical staining revealed that
      tumour cells in scirrhous carcinomas were generally stained more intensively than
      those in other types of carcinomas. On Northern blot analysis the tumour cells
      established from scirrhous carcinoma (KATO-III, OCUM-1 and HSC-39) exhibited
      relatively strong signals compared with those from non-scirrhous carcinoma (MKN
      28 and MKN-45). In the culture media of scirrhous carcinoma cells, the active
      form of TGF-beta 1 was detected, while in those of the non-scirrhous carcinoma
      cells the latent form was demonstrated by both colony and radioreceptor assays.
      The culture medium from KATO-III showed strong stimulating activity of collagen
      synthesis in fibroblasts, and this activity was partially neutralised by an anti
      TGF-beta 1 antibody. These results suggest that tumour cells in scirrhous
      carcinoma produce more active-form TGF-beta 1 than does non-scirrhous carcinoma
      and thus is partially responsible for the observed enhanced collagen deposition
      in the region.

PMID- 8142267
TI  - Risk of new primary cancer in patients with oropharyngeal cancer.
AB  - The relative risk of subsequent cancers was evaluated for a total of 9,092
      patients with lip and oropharyngeal cancer recorded between 1953 and 1989 in the
      nationwide Finnish Cancer Registry. The observed numbers of patients were
      compared with those expected on the basis of the incidence rates in the Finnish
      population. There were 1,130 patients (12%) with a new cancer. The standardised
      incidence ratio (SIR) of contracting a new primary cancer was 1.2 for lip cancer
      patients (95% CI 1.1-1.3) and 1.4 for patients with oropharyngeal cancer (95% CI
      1.2-1.4). Among lip cancer patients, a statistically significant excess risk was
      found for subsequent cancers in the oropharyngeal area (SIR 1.9, 95% CI 1.1-3.1),
      larynx (SIR 2.0, 95% CI 1.2-2.9) and lung (SIR 1.4, 95% CI 1.3-1.6), i.e. for
      cancers with tobacco aetiology. Among patients with oropharyngeal cancer there
      was an excess of lip cancer (SIR, 3.5, 95% CI 1.5-6.9), lung cancer (SIR 1.8, 95%
      CI 1.3-2.3) and leukaemia (SIR 2.3, 95% CI 1.0-4.3). Radiotherapy for the first
      primary did not increase the risk of new cancer.

PMID- 8142269
TI  - British Connective Tissue Society Meeting. Cambridge. Abstracts.

PMID- 8142268
TI  - Verapamil: what is the mechanism of its anticarcinogenic activity?

PMID- 8142270
TI  - Rodent models of alcoholic liver disease.

PMID- 8142271
TI  - Langerhans cell migration patterns from sheep skin following topical application
      of carcinogens.
AB  - Application of tumour promoters or complete chemical carcinogens to skin alters
      the density and/or morphology of epidermal Langerhans cells (LC). To examine the
      hypothesis that these chemical carcinogens alter LC migration kinetics from the
      epidermis, pseudoafferent lymphatic vessels draining defined areas of carcinogen
      treated sheep skin were cannulated and the number of LC migrating enumerated
      using indirect immunofluorescence and flow cytometry. The complete carcinogen
      benzo[a]pyrene (BP) and the tumour promoter 12-O-tetradecanoylphorbol-13-acetate
      (TPA) caused an immediate two to four-fold increase in the rate of LC migration,
      while the tumour initiator urethane did not alter LC migration. The antigenicity
      of the carcinogens utilized was assessed in contact hypersensitivity experiments
      in mice. BP and TPA were mildly antigenic whereas urethane failed to initiate a
      contact hypersensitivity response in sensitized mice. It is concluded that the
      initial increase in LC migration from skin following the application of the
      tumour promoter TPA and the complete carcinogen BP is partly due to LC
      recognizing these carcinogens as antigens.

PMID- 8142272
TI  - Specific receptors for dengue virus-induced suppressor cytokine on macrophages
      and lymphocytes.
AB  - The present study was undertaken to investigate the presence of receptors for the
      dengue virus-induced suppressor cytokine (SF) on mouse macrophages (Mphi), T and
      B lymphocytes. It was observed that 125I-SF bound to T and B cells to a variable
      degree through both high and low affinity receptors. The numbers of high affinity
      receptors on T and B cells were 35,000 and 16,000/cell respectively and those of
      low affinity receptors were 0.72 x 10(6) and 0.33 x 10(6)/cell respectively. The
      binding of 125I-SF was also shown by removal of the biological activity following
      adsorption on Mphi monolayers. The suppressor activity was inhibited by
      pretreatment of SF with anti-SF-antisera. The binding of 125I-SF to Mphi was
      saturable, reversible and dependent on pH, time and temperature. This shows the
      presence of a specific receptor for SF on mouse Mphi, T and B lymphocytes.

PMID- 8142273
TI  - Idiopathic megacolon in the BB rat.
AB  - It has been assumed that idiopathic megacolon occurring in the spontaneously
      diabetic BB rat results from metabolic decompensation associated with diabetes.
      In a large prospective necropsy study we have documented the incidence of
      idiopathic megacolon and its distribution between diabetic and non-diabetic
      animals in the BB rat colony in Edinburgh. A significantly increased incidence of
      megacolon was found in non-diabetic rats in the diabetes-prone subline compared
      with diabetic rats in the diabetes-prone subline and with non-diabetic rats in
      the diabetes-resistant subline. Affected animals were found to have an
      inflammatory infiltrate in the wall of the large bowel with destruction of both
      autonomic ganglia and muscularis propria. These necropsy observations indicate
      that megacolon cannot be a result of the metabolic disturbance due to the
      hyperglycaemia associated with diabetes.

PMID- 8142274
TI  - An experimental transplantable osteosarcoma with spontaneous pulmonary metastasis
      in hamsters.
AB  - Animal models of osteosarcoma with spontaneous pulmonary metastasis which retain
      metastatic capacity and osteoid formation after serial passages have been
      reported infrequently. In this communication we describe some biological features
      of a transplantable osteosarcoma, Os515, induced by BK-virus in Syrian golden
      hamsters. The subcutaneously transplanted tumours in 2-week-old animals grew
      progressively until death, with a mean survival time of 32 days. Distant
      metastases occurred only in the lungs in all animals. The histological appearance
      was osteosarcoma of osteoblastic type. Enzyme-histochemical staining showed
      alkaline phosphatase activity in many cells and beta-glucuronidase activity in
      few cells. Tumours transplanted intramuscularly in the hind limbs were amputated
      radically at 5 or 11 days. A small number of animals died from lung metastases
      without local relapse during the observation period of 140 days after grafting.
      All the control hamsters bearing unamputated tumours died much earlier. Necropsy
      revealed large metastatic nodules in the lungs of limb-amputated animals and
      small diffuse nodules in the lungs of untreated control animals. The development
      of lung metastases was monitored by soft X-ray without sacrificing the animals.
      This model will be useful in studies of mechanisms of metastasis and for the
      experimental treatment of osteosarcoma.

PMID- 8142276
TI  - Use of full-thickness calvarial bone grafts for cervical spinal fusions in
      pediatric patients.
AB  - The use of full-thickness calvarial bone grafts for cervical spinal fusions
      appears to be effective and safe in pediatric patients requiring stabilization of
      the cervical spine. The grafts create solid fusions, better immediate internal
      stabilization, and the procedure is associated with less morbidity than those
      using autologous grafts of rib or iliac crest.

PMID- 8142275
TI  - An evaluation of experimental models of glomerulonephritis.

PMID- 8142277
TI  - Value of thallium-201 SPECT imaging in childhood brain tumors.
AB  - Thallium-201 chloride single photon emission computed tomography (201Tl SPECT)
      has been proposed as a diagnostic tool in the assessment of patients with brain
      tumors. We performed SPECT scans coupled with magnetic resonance imaging (MRI) in
      children with brain tumors to determine the sensitivity and potential value of
      SPECT in neuro-oncology. Each patient was injected with 2.5-3.0 mCi of thallium
      chloride, followed by technetium-99m HMPAO (5-15 mCi) to assess cerebral
      perfusion. 201Tl uptake was imaged with triple-headed SPECT in 20/24 (83%)
      histologically and anatomically diverse neoplasms with MRI-measurable residual
      disease, including 13/16 (80%) posterior fossa tumors. 201Tl SPECT demonstrated
      uptake in tumors with MRI volumes ranging from 0.03 to 60 cm3. 201Tl SPECT
      imaging was not correlated with the following MRI features: gadolinium
      enhancement, necrosis, exophytic, unicentric and multicentric. 201Tl uptake was
      not detectable in patients with tumors of maldevelopmental origin or
      radionecrosis. It is suggested that 201Tl SPECT is an important imaging adjunct
      in the assessment of children with brain tumors.

PMID- 8142278
TI  - The surgical and natural morbidity of aggressive resection for posterior fossa
      tumors in childhood.
AB  - The morbidity associated with gross total removal of pediatric posterior fossa
      tumors is well recognized although it is rarely isolated from other factors that
      comprise the management morbidity for these tumors. This study reviews (1) the
      operative and postoperative complications in 105 patients and (2) the
      neurological morbidity in a subset of 91 patients undergoing gross total removal
      of their tumor between 1982 and 1992. Gross total removal was achieved in 102
      patients with a single procedure. Two patients with residual tumor underwent
      early repeat craniotomy for excision and 1 is being followed without repeat
      resection. Intra- and postoperative complications occurred in 33 patients and
      included hematoma requiring craniotomy (3), gastrointestinal hemorrhage (2),
      hydrocephalus requiring shunt placement (9), wound problems (4), and
      pseudomeningocele formation requiring additional treatment (5). Delayed onset
      hydrocephalus requiring shunting occurred in 2 patients and spinal deformity in 4
      patients. Worsening of preoperative deficit (new cranial nerve palsies, worsening
      ataxia, bulbar dysfunction including apnea, mutism and seizures) occurred in 41%
      of patients operated on for primitive neuroectodermal tumors (PNET) (14/34), 53%
      of ependymomas (10/19), and 30% of astrocytomas (15/50). No patient who had a
      choroid plexus tumor was worsened by the procedure. Complete recovery of new
      postoperative deficits occurred in 14% of PNET (2/14), 50% of ependymoma (5/10)
      and 47% of astrocytoma (7/15), most often within 6 months of the procedure.
      Residual neurological morbidity, due to persistence of preoperative symptoms or
      due to deficits that occurred as the result of the surgical procedure, was
      assessed in a subgroup of 91 patients followed for an average of 48 months (2-147
      months). This assessment did not include morbidity due to adjuvant therapy. Sixty
      two percent of patients continued to exhibit abnormal cerebellar or bulbar signs.
      Forty-three percent of the total population exhibited limitation in function due
      to residual deficit. Only 38% of patients were both functionally normal and had a
      normal neurological examination at last follow-up.

PMID- 8142280
TI  - Change in spinal curvature following release of tethered spinal cord associated
      with spina bifida.
AB  - Changes in spinal curvature, scoliosis, kyphosis and lordosis are associated with
      the growth of patients with myelomeningocele. Previous investigators have stated
      that progressive developmental scoliosis is related to tethered spinal cord. In
      order to investigate the relationship of tethered spinal cord release to
      progression of spinal curvature, we surveyed the medical records of 262 patients
      with a history of one or more tethered spinal cord release. For 216 of these
      patients, a total of 2,369 serial spine x-rays, obtained over a 20-year period,
      were reviewed by the standard Cobb method for progression of scoliosis, thoracic
      kyphosis and lordosis. In addition, the serial spine x-rays of 74 patients
      without clinical findings of tethered spinal cord were collected and reviewed for
      comparison of progressive scoliosis and kyphosis. One hundred and sixty normal
      lumbar x-rays were evaluated to compare the progression of the lordotic curve in
      patients with tethered cord release with a normal population. Progression of
      scoliosis plateaued or declined following release of tethered cord in patients
      with lumbar and sacral level lesions, however, tether release did not halt the
      progression of scoliosis in the thoracic level group. Tethered cord release
      altered the course of lordosis in L1 through L3 level lesions, but had little
      affect on the normal progression of lordosis in patients with L4, L5 or sacral
      level lesions. Finally, tethered spinal cord release appears to be associated
      with a decrease in the incidence and magnitude of kyphosis.

PMID- 8142279
TI  - Predominance of pilocytic histology in dorsally exophytic brain stem tumors.
AB  - We report the magnetic resonance imaging (MRI) and clinico-histologic
      characterization of dorsally exophytic brain stem gliomas (DEBSGs). Between 1983
      and 1991, 12 of 51 patients evaluated for the diagnosis of brain stem glioma were
      found to have DEBSGs emanating from the pons, pontomedullary junction or medulla.
      Eleven of the 12 patients had classic juvenile pilocytic astrocytomas. Unlike
      most other brain stem tumors, these patients were young (median 38 months, range
      17-75), had a relatively long duration of symptoms (median 7 months, range 2-24)
      and displayed signs of increased intracranial pressure with limited cranial nerve
      paresis, absence of pyramidal tract findings, and near normal brain stem auditory
      evoked potentials. MRI characteristically showed sharply demarcated lesions with
      decreased signal intensity on T1, and increased intensity on T2 sequences. Except
      for cystic areas, these tumors showed bright, uniform enhancement after
      gadolinium-DTPA. In all patients, 50-100% of the tumor volume could be resected.
      Three of 10 patients who received no immediate postoperative treatment eventually
      demonstrated disease progression, and 2 patients with subtotal resections who
      were treated with radiation and/or chemotherapy postoperatively remain disease
      free for extended periods of time. The only death occurred in the 1 patient
      treated with chemotherapy who died of secondary leukemia. The overall and
      progression-free survival of these patients at 2 years is 100 and 67% as compared
      to 18 and 21%, respectively, for other concomitantly treated nonexophytic brain
      stem gliomas.2+ the ability to achieve significant degrees of resection.

PMID- 8142281
TI  - Effects of selective dorsal rhizotomy for spastic diplegia on hip migration in
      cerebral palsy.
AB  - In spastic diplegia of cerebral palsy, migration of the femoral head beyond a
      lateral edge of the acetabulum is a common orthopedic deformity and requires
      surgical treatment. We investigated whether selective dorsal rhizotomy for
      spastic diplegia halts or exacerbates lateral hip migration. The Reimers
      migration percentage computed from preoperative and postoperative hip radiographs
      was used as an index of the severity of lateral hip migration in all 134 hips of
      67 children examined. At the time of rhizotomy, 38 patients were between 2 and 4
      years of age and 29 were between 5 and 11 years of age. The follow-up period
      ranged from 6 to 10 months in 20 patients and from 15 to 46 months in 47
      patients. Overall, the MP remained unchanged in 75% decreased in 17% and
      increased in 7%; thus, 93% of all hips examined were stable radiographically.
      Although most patients experienced postoperative hip stability, there was a
      significant trend for patients with greater preoperative migration to show
      decreased postoperative migration. The preoperative ambulatory status of patients
      had no impact on hip stability after dorsal rhizotomy. By the last follow-up,
      only 1 patient had undergone orthopedic operations for a persistent hip
      deformity. The results suggest that in children with spastic diplegia, selective
      dorsal rhizotomy halts lateral hip migration in the great majority of cases.

PMID- 8142282
TI  - Changes of synapse-related proteins (SVP-38 and drebrins) during development of
      brain in congenitally hydrocephalic HTX rats with and without early placement of
      ventriculoperitoneal shunt.
AB  - Hydrocephalic and nonhydrocephalic HTX rats served, respectively, as experimental
      and sham operation animals. They were treated by insertion of
      ventriculoperitoneal (V-P) shunts at 7 days after birth (early shunt). Monoclonal
      antibodies against synaptic vesicle proteins (SVP-38) and developmentally
      regulated brain proteins (drebrins) were used to assess these two synapse-related
      proteins by means of either a quantitative immunohistochemical method or a
      qualitative immunoblot analysis. The amount of SVP-38 progressively increased
      during a 3-week period after birth in both hydrocephalic and nonhydrocephalic HTX
      rats, but decayed suddenly at 4 weeks after birth in hydrocephalic HTX rats. When
      the hydrocephalic HTX rats were treated with V-P shunts, such perturbations in
      postnatal changes of SVP-38 were prevented completely. In nonhydrocephalic HTX
      rats, only the embryonic form of drebrins was detected at 1 day after birth, and
      this disappeared at the end of the 3rd week. The adult form of drebrin could be
      detected at 1 week after birth, and this completely replaced the embryonic form
      by 3 weeks of age. However, the postnatal decay of the embryonic form was
      considerably delayed in hydrocephalic HTX rats. These observations indicate that
      since synaptogenesis in the brain of hydrocephalic HTX rats has already been
      disturbed at the prenatal periods, which is the initial process of hydrocephalus,
      early shunt treatment of hydrocephalus would be beneficial not only for repairing
      but also for preventing impaired synaptogenesis.

PMID- 8142283
TI  - The P1: insights into attention and arousal.
AB  - The authors provide evidence that four mesencephalic nuclei, two of which are
      cholinergic and two of which are catecholaminergic, serve as oscillators capable
      of modulating a number of interrelated rhythmic functions. These include sleep
      wake cycles, locomotion, blood pressure, respiratory rate, heart rate,
      mastication, micturition, and saccadic eye movements. The P1 auditory evoked
      potential is generated by ascending cholinergic projections from one of these
      nuclei, the pedunculopontine nucleus, and thus serves as a clinical tool to
      monitor the integrity of this system.

PMID- 8142284
TI  - Cost and outcome in a series of shunted premature infants with intraventricular
      hemorrhage.
AB  - This study examines cost and outcome in a series of 50 low birthweight infants
      who suffered severe intraventricular-periventricular hemorrhage and subsequently
      required ventriculoperitoneal shunting. Although nearly one third of these
      children might achieve some degree of self-sufficiency, a cost-benefit analysis
      in this shunted population is not encouraging.

PMID- 8142285
TI  - Echocardiographic detection of intracardiac thrombi complicating ventriculo
      atrial shunt. Report of two cases.
AB  - Right atrial thrombi are rare but serious complications of ventriculoatrial (VA)
      shunts. Two hydrocephalic patients who received a VA shunt developed
      thromboembolic complications. The initial manifestation was malfunction of the
      distal end of the shunt and right heart failure. Bidimensional echocardiography
      demonstrated an intracardiac mass on the distal intra-auricular end of the shunt.
      Pulmonary scan showed multiple emboli even in the asymptomatic patient. This
      demonstrates the important role of bidimensional echography as a noninvasive
      diagnostic technique for this particular complication of a VA shunt. Medical and
      surgical treatment modalities are discussed.

PMID- 8142286
TI  - Needle aspiration of acute subdural hematomas in infancy.
AB  - This report documents the ability of acute subdural hemorrhage to be easily and
      completely aspirated percutaneously through the open sutures of infants,
      obviating the need for open drainage. The technique has recently been used in 4
      cases.

PMID- 8142287
TI  - Hydatid infestation of the brain: difficulties with computed tomography diagnosis
      and surgical treatment.
AB  - The radiological, surgical and pharmacological management of 11 children with
      cerebral hydatid disease is presented with special emphasis on the varying CT and
      MRI appearances and the surgical difficulties we have encountered. All but 2 had
      enhanced CT scanning and 2 had an MRI. The typical CT appearance of a large non
      enhancing cyst of CSF density with minimal oedema was only seen in 3 children.
      Atypical appearances included irregularity of the cyst wall contour (2),
      enhancement of the surrounding rim (3), isodensity or heterogeneity of the cyst
      content (4), surrounding oedema (4) and globular as opposed to curvilinear
      calcification (2). Complete intact cyst removal was achieved in 3 patients. The
      reasons for puncturing the cysts or rupturing them at operation were failure to
      make a definitive pre-operative diagnosis (5), dense adhesions to the skull, dura
      or falx (3) and the misdiagnosis of an arachnoid cyst and the subsequent
      placement of a cystoperitoneal shunt (1). Pathological examination suggests that
      the degree of the inflammatory response to the ectocyst may determine the
      enhancement characteristics and the ease of surgical removal. There was 1
      recurrence which responded well to four 28-day treatment cycles of albendazole.

PMID- 8142288
TI  - Complications of central nervous system hydatid disease.
AB  - Central nervous system hydatid cyst disease presents with different clinical
      pictures depending on the involvement of cerebral and spinal structures. The
      majority of cerebral echinococcosis cases are in the pediatric age group, mostly
      involving the white matter, and their treatment is mainly surgical. Complications
      of this entity depend on several factors including the location, size, and
      multiplicity of the cysts, as well as the presence of contamination. The most
      common complication is a rupture of the cyst into the subarachnoid space which
      leads to widespread dissemination followed by severe inflammatory or anaphylactic
      response. However, vertebral lesions are usually invasive and cause neurological
      symptoms due to compression. Almost all patients complain of radicular pain and
      motor deficits; and up to one half of patients present with paraparesis. This
      paper examines the natural history and complications which may arise during the
      treatment of cerebral and vertebral hydatid cysts, and discusses their clinical
      management.

PMID- 8142289
TI  - Intracranial fluid dynamics. Interrelationship of CSF and vascular phenomena.
      1983.

PMID- 8142290
TI  - Occipital reduction-biparietal widening technique for correction of sagittal
      synostosis.
AB  - In the older infant with a marked skull deformation from sagittal synostosis a
      midline craniectomy will not produce an optimal cosmetic result as the brain
      grows at a much reduced rate and cannot provide the impetus for passive
      correction of the deformity. An operative technique is described whereby the
      occipital prominence is reduced, the biparietal diameter widened, and the height
      of the calvarium lowered at the vertex. Although the frontal bossing is not
      directly addressed the changes in the remainder of the calvarium render the
      bossing of little cosmetic relevance and has not been a long-term problem in the
      group of patients treated with this technique. The amount of manipulation,
      operative time, and blood loss with the procedure is comparable to others
      reported. This technique does not have the potential to raise intracranial
      pressure if one takes care to avoid undue compression on the major dural venous
      sinuses. There have been no significant bony defects and no patient has required
      reoperation. The cosmetic results have been excellent.

PMID- 8142291
TI  - Androgen-dependent expression of cystatin-related protein (CRP) in the exorbital
      lacrimal gland of the rat.
AB  - Cystatin-related protein (CRP), also known as 20 (22)-kDa glycoprotein is
      expressed not only in the ventral prostate, but also in the lacrimal gland of
      adult male rats. In this study the expression of CRP in androgen-treated female
      animals is studied. CRP mRNA is absent in the lacrimal gland of untreated adult
      female rats, but can be induced by androgens, although this induction is slower
      than in castrated male rats. Estradiol, progesterone or glucocorticoids have no
      effect. In testicular feminized rats, however, CRP mRNA is not induced in the
      lacrimal gland by androgens. At the protein level, the presence of CRP in tears
      of adult male rats is demonstrated. In female animals or castrated male animals
      CRP can be induced by androgens in a dose-dependent way. Here also the induction
      is slower in female rats, even during secondary induction after previous full
      stimulation by androgens. These results indicate that androgens and a
      functionally normal androgen receptor are essential for the expression of CRP in
      the lacrimal gland. The time course of induction depends on the dose of
      androgens, the previous contact with androgens, the duration of the androgen-free
      interval and the sex of the animals.

PMID- 8142292
TI  - Effect of 17 beta-estradiol on immunoglobulin secretion by human tonsillar
      lymphocytes in vitro.
AB  - Sex steroid hormones play a role in the complex network of immune responses but
      the mechanism of their action is still unclear. Effects of a wide range of doses
      of 17 beta-estradiol (E2: 0.2-100 ng/ml) on human tonsillar lymphocyte cultures
      were examined. B and T lymphocyte enriched preparations were stimulated with
      various concentrations of interleukin-2 and the production of immunoglobulin was
      measured. Addition of E2 increased B cell immunoglobulin production in a T cell
      dependent way with intact T cells being obligatory. The effects of E2 were also
      examined on DNA synthesis by tonsillar T cells. E2 alone caused a significant
      increase in T cell DNA synthesis. With phytohaemagglutinin-stimulated T cell
      cultures there was a significant increase in DNA synthesis with E2 at
      pharmacological doses. Different cell surface and activation markers (including
      CD25, p75, HLA-DR, CD28) on tonsillar lymphocytes were also studied after
      exposure to E2. The presence of E2 made no significant difference in the
      expression of the markers either alone or when the activation antigens were
      induced by other stimuli. We have shown that intact T cells are needed for the
      action of E2 on tonsillar B lymphocyte differentiation and have excluded several
      mechanisms of action of E2 since common activation antigens are unaffected.

PMID- 8142293
TI  - Glucocorticoid actions on synaptic plasma membranes: modulation of
      [125I]calmodulin binding.
AB  - The effects of corticosterone on Ca(2+)-dependent binding of [125I]calmodulin to
      purified synaptic plasma membranes (SPM) from rats brain were characterized. The
      enhancement of [125I]calmodulin binding was a sigmoidal function of steroid
      concentration, with the maximal increase (> 55% above control) occurring at a
      steroid concentration of 1 x 10(-6) M and EC50 estimated at 1-2 x 10(-7) M. Other
      glucocorticoids including hydrocortisone, dexamethasone and triamcinolone
      produced similar effects, whereas steroids without glucocorticoid activity such
      as 11-deoxycortisol, 11-deoxycorticosterone and cholesterol were ineffective. The
      steroid-induced increase of binding was correlated with an increase of membrane
      affinity for [125I]calmodulin as shown by Scatchard analysis, and a decrease of
      the rate of dissociation of [125I]calmodulin from the membranes as shown by
      kinetic analysis. Arrhenius analysis indicates that [125I]calmodulin binding was
      influenced by lipid transition of the membranes and that corticosterone resulted
      in a shift of membrane transition toward a higher temperature. Since a variety of
      biochemical processes associated with synaptic membranes are dependent upon
      calmodulin for their regulation, we hypothesize that the effects of
      glucocorticoids in promoting membrane binding of calmodulin may lead to a cascade
      of alterations in synaptic function.

PMID- 8142294
TI  - RU 58,668, a new pure antiestrogen inducing a regression of human mammary
      carcinoma implanted in nude mice.
AB  - RU 58,668, a new steroidal antiestrogen, has been synthesized. Its in vitro and
      in vivo pharmacological activities have been compared to those of tamoxifen and
      ICI 182,780. In vitro, it displayed affinities for human and murine estrogen
      receptors equivalent to those of 4-hydroxy-tamoxifen, along with moderate
      affinities for progestin and glucocorticoid receptors. RU 58,668 proved to be a
      potent antiproliferative agent on MCF-7 cells stimulated by estradiol, or by
      exogenous or endogenous growth factors (IC50, 0.01 nM). It also inhibited the
      growth of the insulin-stimulated T47D cell line. In vivo, RU 58,668 displayed a
      total anti-uterotrophic activity in mice or rats without exhibiting any agonistic
      effect. Moreover, RU 58,668 was the only antiestrogenic compound tested so far to
      be able to induce a long term regression of human mammary MCF-7 tumors implanted
      in nude mice, suggesting its potential use for the treatment of advanced breast
      cancer.

PMID- 8142295
TI  - Epristeride is a selective and specific uncompetitive inhibitor of human steroid
      5 alpha-reductase isoform 2.
AB  - Specificity of an enzyme inhibitor can have profound implications upon the
      compound's therapeutic potential, utility and safety profile. As potent
      inhibitors of human steroid 5 alpha-reductase (SR) the 3-androstene-3-carboxylic
      acids, or steroidal acrylates, may be useful in treatment of diseases such as
      benign prostatic hyperplasia for which 5 alpha-dihydrotestosterone (DHT) appears
      to be a causative agent. To determine its specificity profile, the interactions
      of a representative compound from this class, N-(t-butyl)androst-3,5-diene-17
      beta-carboxamide-3-carboxylic acid (epristeride, SK&F 105657), have been studied
      with 7 other steroid processing enzymes and 5 steroid hormone receptors. The
      affinity of epristeride for each of these 12 potential targets was found to be at
      least 1000-fold weaker than that for SR, the intended target. In addition, using
      samples of the individually expressed two known forms of human SRs, epristeride
      has been shown to be a selective inhibitor of the recombinant human SR type 2,
      the predominant activity found in the prostate of man. Nonetheless, the
      mechanisms of SR inhibition for both isoenzymes involve formation of a ternary
      complex with epristeride, NADP+, and enzyme. Epristeride, consequently, has been
      shown to be an uncompetitive inhibitor versus steroid substrate of both human SR
      isoenzymes. These results suggest that this 3-androstene-3-carboxylic acid is a
      specific and selective inhibitor of the human type 2 SR, and that epristeride is
      an attractive compound for further investigation as a safe and effective
      therapeutic agent in the potential treatment of disease states associated with
      DHT-induced tissue growth.

PMID- 8142296
TI  - Estrogen action on hepatic synthesis of angiotensinogen and IGF-I: direct and
      indirect estrogen effects.
AB  - In the present study effects of estrogens (natural estradiol and synthetic
      ethinyl estradiol) on liver derived proteins (angiotensinogen, IGF-I) were
      investigated in vivo in ovariectomized rats and in vitro in a rat hepatoma cell
      line (Fe33). The aim of this study was to establish both an animal and an in
      vitro model for quantification of the hepatic activity of given estrogenic
      compounds, and to study underlying mechanisms as regards the question of direct
      or indirect mode of estrogen action. In ovariectomized rats subcutaneous (s.c.)
      treatment for 11 days with either estradiol (E2) or ethinyl estradiol (EE) (dose
      range 0.1-3 micrograms/animal/day) induced a comparable dose-dependent increase
      in uterine weight indicating a similar estrogenic potency of the two estrogens.
      Equipotency was also found as regards the effects on IGF-I plasma levels which
      dose-dependently decreased by about 50% at the highest dose tested (3
      micrograms/animal/day). The decrease in IGF-I serum levels was accompanied by a
      significant 40% decrease in liver IGF-I mRNA. In contrast angiotensinogen plasma
      levels were affected only by EE (60% increase for the 3 micrograms/animal/day
      dose) but not by E2. When rats, in addition to ovariectomy, were also
      hypophysectomized (substituted with human growth hormone and dexamethasone)
      angiotensinogen again increased by 80% upon administration of 3
      micrograms/animal/day EE, whereas IGF-I remained unaffected by EE. In a rat
      hepatoma cell line (Fe33) which is stably transfected with an estrogen receptor
      expression plasmid, 10 nmol/l EE for 24 h caused a 2.4-fold increase in
      angiotensinogen mRNA level. We conclude from our studies that estrogen effects on
      angiotensinogen serum levels in the rat are direct effects via the hepatic
      estrogen receptor, whereas estrogen effects on IGF-I serum levels are indirect
      effects, the primary target of estrogen action being probably the pituitary. The
      changes in angiotensinogen serum levels in the rat model are comparable to the
      situation in humans indicating the rat model and the Fe33 model to be useful
      tools to study the hepatic activity of estrogenic compounds.

PMID- 8142297
TI  - Effect of aromatase inhibitors on estrogen 2-hydroxylase in rat liver.
AB  - The effect of aromatase inhibitors, 4-hydroxyandrostenedione, CGS 16949A and
      aminoglutethimide on the inhibition of estrogen 2-hydroxylase activity in rat
      liver microsomes in vitro and on its induction in vivo has been examined.
      Estrogen 2-hydroxylase was found to have over twice the affinity for estradiol
      compared to estrone. Using high pressure liquid chromatography and employing
      estradiol as a substrate, the IC50 values were 2.2, 98, 110 and 908 microM for
      the reference compound ketoconazole and the aromatase inhibitors, 4
      hydroxyandrostenedione, CGS 16949A and aminoglutethimide, respectively. Similar
      IC50 values were obtained using estrone as a substrate and by a tritiated water
      method employing estradiol as a substrate. The Km value for estrogen 2
      hydroxylase with estradiol as a substrate using a tritiated water method was 4.3
      microM with a Vmax of 11.89 nmol/h/mg. Ketoconazole, CGS 16949A and
      aminoglutethimide exhibited non-competitive inhibition whereas 4
      hydroxyandrostenedione appeared to be a competitive inhibitor of estrogen 2
      hydroxylase. The Ki values were 2.6, 72, 114 and 958 microM for ketoconazole, 4
      hydroxyandrostenedione, CGS 16949A and aminoglutethimide, respectively. All three
      aromatase inhibitors were weak inhibitors of estrogen 2-hydroxylase as compared
      to the reference drug, ketoconazole. Following treatment of rats with
      aminoglutethimide (40 mg/kg/day; i.p.; for 3 days), estrogen 2-hydroxylase
      activity was increased by 28 and 30% using estradiol and estrone as substrates,
      respectively. Following treatment of rats with CGS 16949A (2 mg/kg/day; p.o.; for
      3 days), the corresponding increase in estrogen 2-hydroxylase activity was 48 and
      44%. The results of this study indicate that the aromatase inhibitors,
      aminoglutethimide and CGS 16949A are only weak inhibitors of estrogen 2
      hydroxylase activity in vitro and show no evidence of inhibition in vivo. On the
      contrary, there was some evidence to suggest that both aminoglutethimide and CGS
      16949A induce estrogen metabolism following repeated administration. Therefore,
      aminoglutethimide and CGS 16949A may lower estrogen levels not only by primarily
      inhibiting their synthesis but also by inducing the metabolism of estrogens.

PMID- 8142298
TI  - Metabolism of estrone sulfate by normal breast tissue: influence of menopausal
      status and oral contraceptives.
AB  - The metabolism of [3H]estrone sulfate ([3H]E1S) was studied in normal breast
      tissue from 10 premenopausal women without oral contraceptives (OC), in 12 OC
      users and in 9 untreated postmenopausal women. [3H]E1S was converted into estrone
      ([3H]E1) and estradiol-17 beta ([3H]E2) by tissue samples from all three groups
      of women, with only minor formation of other unconjugated compounds. The rate of
      [3H]E2 formation was significantly higher in premenopausal women without OC than
      in postmenopausal women. Among premenopausal women, OC users had a significantly
      lower rate of total hydrolysis and of [3H]E1 formation than non-users. The rate
      of total hydrolysis of [3H]E1S in normal breast tissue from all three groups of
      women was similar to that in muscle, but the rate of [3H]E2 formation was ten
      times higher. Both total hydrolysis rate and rate of [3H]E2 formation were
      significantly lower in normal breast tissue than in breast carcinoma and in
      normal and neoplastic endometrium. The specific ability of normal breast tissue
      to convert E1S into the terminal biologically active estrogen E2 may be important
      for estrogenic stimulation of the breast in subjects with low circulating E2
      levels. The lower rate of E1 formation in OC users may reflect an inhibitory
      effect of the progestagen compound in such preparations.

PMID- 8142299
TI  - Investigation of a 17 beta-estradiol-monoclonal antiestradiol antibody binding
      mechanism using dilute solutions of organic solvents.
AB  - Quantitative understanding of steroid hormone transport and receptor-mediated
      action requires knowledge of the bonding forces involved in each steroid-protein
      complex and the effects of a biological environment on these forces. An approach
      to these problems using dilute solutions of water-miscible organic solvents, with
      a range of polarity, dielectric and hydrogen bonding properties, was tested on an
      estradiol-antiestradiol antibody binding system on the basis that comparing the
      effects of the solvents would both permit the importance of hydrophobic and
      hydrogen bonding to be differentiated and give information on the effects of the
      environment on the reaction. The results were compared with thermodynamic
      measurements. All the solvents reduced the Gibbs free energy of binding as a
      function of their concentration in the medium. The decreases were virtually a
      monotonic function of their dielectric constant, indicating reduced hydrogen
      bonding. Analysis of the decreases in terms of the solvents' hydrogen bonding and
      polarity properties supported this. Thermodynamic measurement showed the binding
      reaction was enthalpy-driven with, overall, a slightly unfavorable entropy
      contribution. This again showed the hydrophobic effect was not the main bonding
      force. The most deleterious solvent, iso-propanol, not only decreased the
      enthalpic contribution to binding but rendered the entropic contribution more
      favorable. This approach still does not allow the relative importance of hydrogen
      bonding and van der Waals contacts in the actual binding to be differentiated but
      it does give indications on how a biological environment may affect a steroid
      protein binding reaction in vivo.

PMID- 8142300
TI  - The effect of prolactin, human chorionic gonadotropin, insulin and insulin-like
      growth factor 1 on adrenal steroidogenesis in isolated guinea-pig adrenal cells.
AB  - The controlling mechanism for adrenal androgen production has not been
      elucidated. The presence of receptors for prolactin, human chorionic gonadotropin
      (hCG), insulin and insulin-like growth factor 1 (IGF-1) in the adrenal cortex
      raises the possibility of their involvement in the control of adrenal
      steroidogenesis. This study was undertaken to investigate the effects of
      prolactin, hCG, insulin and IGF-1 in the presence and absence of ACTH on cortisol
      and androgen production using isolated guinea-pig adrenal cells. hCG 10(-7) and
      10(-6) M significantly increased cortisol (P < 0.05) production. hCG 10(-6) M
      significantly increased androstenedione (A4) (P < 0.05) production. In the
      presence of ACTH, 10(-12) M, hCG 10(-6) M significantly increased the cortisol (P
      < 0.01) and A4 (P < 0.01) responses. Although the mean cortisol and A4 response
      to ACTH 10(-9) M was reduced in the presence of hCG 10(-6) M, this was not
      statistically significant. Prolactin 10(-8) M increased cortisol (P < 0.01), A4,
      and dehydroepiandrosterone (P < 0.05) production. In the presence of ACTH 10(-12)
      M, prolactin 10(-8) M increased the cortisol and A4 (P < 0.05) responses.
      However, the maximally ACTH-stimulated cortisol and A4 responses were not
      significantly altered in the presence of prolactin 10(-8) M. Insulin 10(-11)-10(
      8) M and IGF-1 10(-10)-10(-7) M resulted in no significant increase in cortisol,
      A4 or dehydroepiandrosterone production. This study suggests that prolactin and
      hCG could play a role in modulation of adrenal steroidogenesis, particularly when
      ACTH levels are low. However, there was no evidence that prolactin or hCG is the
      specific cortical androgen stimulating hormone.

PMID- 8142301
TI  - Endocrine properties of the testosterone 5 alpha-reductase inhibitor turosteride
      (FCE 26073).
AB  - Turosteride was tested in a series of studies for its effect on 5 alpha-reductase
      and for its possible influence on other steroidogenic enzymes and on steroid
      receptors. The compound was found to inhibit human and rat prostatic 5 alpha
      reductases with IC50 values of 55 and 53 nM, respectively, whereas it caused a
      less marked inhibition of the dog enzyme (IC50 2.2 microM). Turosteride showed no
      relevant effect on rat adrenal C20,22-desmolase (IC50 254 microM) and human
      placental aromatase (IC50 > 100 microM), and only at relatively high
      concentrations it caused inhibition of human placental 5-ene-3 beta
      hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-I) (IC50 2.5 microM).
      Turosteride was found to be a selective 5 alpha-reductase inhibitor showing no
      noteworthy binding to receptors for androgens (relative binding affinity, RBA,
      0.004%), estrogens (< or = 0.005%), progesterone (< 0.005%), glucocorticoids (<
      0.01%) and mineralocorticoids (< 0.03%). Its biochemical profile was similar to
      that of finasteride, whereas 4-MA (17 beta-N,N-diethyl-carbamoyl-4-methyl-4-aza-5
      alpha-androstan-3-one) was confirmed to be a non-selective 5 alpha-reductase
      inhibitor, showing a degree of binding affinity to the androgen receptor (RBA
      0.1%) and a marked inhibition of 3 beta-HSD-I (IC50 32 nM). When given orally in
      immature castrated rats together with subcutaneous testosterone propionate (TP)
      for 7 consecutive days, turosteride reduced the ventral prostate and seminal
      vesicle growth promoting effect of TP, with IC50 values of approximately 5 and
      6.7 mg/kg/day, whereas levator ani weight was unchanged. In comparison, 4-MA was
      approx. 3-fold less potent than turosteride in reducing the prostate and seminal
      vesicle weights and caused a marked reduction of levator ani weight, thus showing
      its unselectivity.

PMID- 8142302
TI  - Purification and characterization of 3 alpha/beta-hydroxysteroid dehydrogenase
      from mature porcine testicular cytosol.
AB  - NADPH-dependent 3 alpha/beta-hydroxysteroid dehydrogenase (3 alpha/beta-HSD) was
      purified to apparent homogeneity from testicular cytosol of mature pigs. The
      purified enzyme catalyzes the conversion of 5 alpha-dihydrotestosterone (5 alpha
      DHT) to both 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3
      beta,17 beta-diol. The molecular weight of the enzyme was estimated to be 31 kDa
      by SDS-polyacrylamide gel electrophoresis and 40 kDa by gel filtration
      chromatography indicating that the native 3 alpha/beta-HSD is a monomer. The
      isoelectric point of the purified enzyme was found to be 6.2 by density gradient
      isoelectric focusing and 6.4 by chromatofocusing. The enzyme reduced both 5 alpha
      and 5 beta-DHT, 5 alpha- and 5 beta-dihydroprogesterone, 5 alpha- and 5 beta
      dihydrocortisol, prostaglandin E2, 13,14-dihydro-15-keto-prostaglandin E2 and
      13,14-dihydro-15-keto-prostaglandin F2 alpha. Moreover, the enzyme caused rapid
      reduction of other carbonyl compounds including aldehydes, ketones and quinones.
      The rates of reduction of these compounds are fast relative to the rates of
      reduction of steroids and prostaglandins. The purified enzyme was inhibited by
      AgNO3, SH-reagent, quercetin, hexesterol, stilbestrol, disulfiram and divalent
      cation such as Cu2+, Hg2+ and Cd2+. The two enzymes show certain similarities
      (e.g. molecular weight, cross-reactivity to a common antibody) and certain
      striking differences (e.g. pI, effects of various inhibitors and greater enzyme
      activity towards steroids (neonatal form) or prostaglandins (mature form).
      Reasons are give for suggesting that these enzymes are closely related to
      carbonyl reductase.

PMID- 8142303
TI  - Suramin: an inhibitor of the final steps of the mineralocorticoid pathway?
AB  - The authors used incubated adrenal mitochondria to study the in vitro effect of
      suramin, an antiparasitic drug, on the transformation of corticosterone and 18
      hydroxycorticosterone into aldosterone. The results show that, under conditions
      preserving membrane integrity, the "impermeance" of suramin meant that
      concentrations similar to the plasma-levels reached in treated patients induced
      only slight inhibition of the final intramitochondrial steps in aldosterone
      synthesis. However, suramin strongly inhibited mitochondrial respiration. The
      inhibition of two intramitochondrial mechanisms (respiration and steroid
      synthesis) suggests that the effect of suramin involves partial inhibition of
      metabolic intermediate carriers. The inhibition of the activity of various
      extramitochondrial enzymes involved in intermediate metabolism, suggests that the
      inhibition of steroid biosynthesis can be explained only on the basis of an
      extramitochondrial action of suramin. The action of suramin must, therefore,
      primarily and directly affect extramitochondrial steroid synthesis and only
      indirectly affect intramitochondrial steroid synthesis as a result of an impact
      on the reducing equivalent supply. However, even if suramin does not bind to
      cytochrome P450 11 beta which catalyzes the final steps of aldosterone
      biosynthesis pathway, this does not imply that suramin has no direct effect on
      steroid synthesis within the mitochondria, in addition to its toxic effects,
      particularly if the cell structure is disrupted (as is often the case in tumor
      tissues).

PMID- 8142304
TI  - Monoclonal antibodies against progesterone: effect of steroid-carrier coupling
      position on antibody specificity.
AB  - Monoclonal anti-progesterone antibodies were raised by immunizing mice with
      progesterone coupled through either the C3, C6 or C11 positions to protein
      carrier (bovine serum albumin, BSA). The specificity of four antibodies for a
      range of steroids related to progesterone, some carrying substitutions at various
      ring positions, was studied by competitive inhibition in an ELISA system. The
      results demonstrated that the ring coupling position has a determining effect on
      the cross-reactivity of the antibodies obtained. The patterns of cross-reaction
      were interpreted in the light of the structure of the combining site of an anti
      progesterone antibody (DB3) recently determined by X-ray crystallography, and
      inferences drawn about the orientation of steroid in the combining sites of the
      antibodies studied. Specifically, in two antibodies raised against progesterone
      11-BSA, the orientation of steroid resembled that of the progesterone-DB3
      complex, with positions C11 and C3 exposed and C6 and C20 buried; an antibody
      raised against progesterone-6-BSA bound steroid in an apparently similar
      disposition, except that C6 was exposed and C11 buried; finally, in an antibody
      raised against progesterone-3-BSA, all steroid positions other than C3 were
      apparently buried in the steroid-antibody complex.

PMID- 8142305
TI  - Serum and tissue levels of estradiol during estrogen-induced renal tumorigenesis
      in the Syrian hamster.
AB  - The estrogen-induced renal tumor in the hamster has emerged as a major animal
      model in hormonal carcinogenesis. However, a fundamental aspect of this
      experimental model has as yet not been investigated. In the present study,
      comparisons between the serum and tissue 17 beta-estradiol (E2) levels in cyclic
      female hamsters and corresponding hormone levels in E2-treated castrated male
      hamsters have been made. Data is provided concerning the concentration of
      estrogenic hormones in the serum and target tissue typically required to elicit
      renal tumorigenesis in this species. Serum E2 levels in the cyclic female hamster
      average 79 pg/ml on days 1-2 and 311 pg/ml on days 3-4, attaining a maximum of
      358 pg/ml on day 4 of the cycle. Elevation in uterine, renal and hepatic E2
      tissue levels during days 3-4 of the cycle reflect increases in serum E2 levels
      which were 3.0-, 2.0-, and 2.6-fold higher when compared to day 1 of the cycle in
      these tissues. As expected, serum E2 levels of untreated castrated male hamsters
      did not appreciably vary over a 6 month period of aging and averaged about 32
      pg/ml. Under conditions which produced essentially 100% renal tumor incidence, a
      rapid rise in serum E2 levels, averaging 71.0-fold higher than untreated
      castrated levels, was seen. A steady state serum E2 level of 2400 to 2700 pg/ml
      was maintained from 45-180 days of continuous estrogen treatment. Compared to
      kidneys of untreated hamsters, renal E2 levels in E2-treated hamsters rose only
      on average 5.4-fold between 15-180 days of hormone exposure. Serum levels of E2
      treated hamsters were 5.7- to 8.0-fold higher than those observed in cyclic
      female hamsters on days 3 and 4. However, at these higher E2-treated serum levels
      there was no apparent effect either on weight loss or mortality of the animals.

PMID- 8142306
TI  - In vitro study of the effect of urotensin II on corticosteroid secretion in the
      frog Rana ridibunda.
AB  - Urotensin II is a cyclic dodecapeptide that was originally isolated from the fish
      urophysis, the terminus of a neurosecretory system located in the caudal area of
      the spinal cord. We have recently isolated and characterized urotensin II in the
      brain of a tetrapod, the frog Rana ridibunda. Recent reports, suggesting that
      urotensin II may stimulate cortisol secretion in fish, prompted us to investigate
      the possible effects of fish and frog urotensin II on corticosteroid secretion in
      amphibians. Exposure of perifused frog adrenal slices to goby (Gillichthys
      mirabilis) urophysis extracts induced a marked stimulation of corticosterone and
      aldosterone secretion. In contrast, at concentrations ranging from 10(-10) to 10(
      6) M, synthetic goby urotensin II had no effect on corticosteroid production.
      Similarly, infusion of synthetic frog urotensin II (10(-10) to 10(-6) M) did not
      modify the spontaneous release of corticosterone and aldosterone. In addition,
      frog urotensin II had no effect on ACTH- and angiotensin II-induced secretion of
      corticosteroids. These results show that in frog, urotensin II does not modulate
      spontaneous and ACTH- or angiotensin II-evoked adrenal steroidogenesis.

PMID- 8142307
TI  - A sensitive ELISA for 6 beta-hydroxycortisol in urine using enzyme penicillinase
      (beta-lactamase).
AB  - A sensitive and specific, enzyme labelled immunosorbent assay (ELISA) for 6 beta
      hydroxycortisol in diluted urine using penicillinase was developed. 6 beta
      Hydroxycortisol-21-hemisuccinate was conjugated with enzyme penicillinase.
      Antibody immobilized on a polyvinylchloride ELISA plate (Dynatech) was used for
      separation of bound from free ligand. The sensitivity of the assay was between
      2.0-3.0 pg per well and recovery of 6 beta-hydroxycortisol from urine ranged
      between 85.0-108.0%. The assay is simple, rapid and precise.

PMID- 8142308
TI  - Aromatization of 7 alpha-methyl-19-nortestosterone by human placental microsomes
      in vitro.
AB  - Part of the biological effects of testosterone (T) are mediated by its enzymatic
      reduction to 5 alpha-dihydrotestosterone (DHT) or aromatization to estradiol
      (E2). 7 alpha-Methyl-19-nortestosterone (MENT) is a synthetic androgen that is
      considerably more potent than T. Previous studies have shown that MENT is not 5
      alpha-reduced. The studies reported here were undertaken to determine whether
      MENT undergoes enzymatic aromatization in vitro. Human placental microsomes were
      used as the source of the aromatase. Radioactive or nonradioactive T or MENT was
      incubated with the microsomes in the presence of NADPH and the metabolites
      extracted out with ethyl ether. Following evaporation of ether, the residue was
      dissolved in benzene-petroleum ether and extracted with 0.4 N NaOH which
      selectively removes phenolic metabolites of the androgens. When either
      radioactive T or MENT was incubated with the aromatase in the presence of NADPH,
      there was a 20-fold increase in the amount of radioactivity extracted with NaOH.
      In contrast, if the incubation was carried out in the absence of NADPH or in the
      presence of R76713, an aromatase inhibitor, most of the radioactivity remained in
      the benzene-petroleum ether phase. To further identify the enzymatic reaction
      products, thin layer chromatography (TLC) was performed. The Rf value for MENT
      was 0.22 while that of the major reaction product was 0.34, which corresponded
      with the RF value of the estrogen, 7 alpha-methyl-estradiol (MeE2). This was
      further verified by using a second solvent system for the chromatographic
      separation. In an effort to ascertain whether the metabolites bind to estrogen
      receptors (ER), rat uterine cytosol was used. NaOH extracts of medium following
      incubation of nonradioactive MENT with microsomes showed competitive inhibition
      of [3H]E2 binding to rat uterine ER. Furthermore, after [3H]MENT was incubated
      with microsomes, the radioactive metabolite extracted in NaOH showed specific
      binding to the ER which could readily be displaced with E2 or MeE2. These results
      indicate that like T, MENT undergoes enzymatic aromatization.

PMID- 8142309
TI  - Oxysterol sensitive and resistant lymphoid cells: correlation with regulation of
      cellular nucleic acid binding protein mRNA.
AB  - Oxygenated derivatives of cholesterol inhibit cholesterol synthesis, prevent
      lymphoid cell growth, and evoke cell death. We have employed a novel selection
      method to isolate M10 cells, a line of oxysterol-resistant cells, from the
      sensitive clone CEM C7. Concentrations of the potent sterol 25-hydroxycholesterol
      that occupy the oxysterol binding protein cause cell death in CEM C7, but not in
      M10 cells. Both cell lines have similar amounts of the oxysterol binding protein
      with similar affinities for oxysterol. However, in neither line are the levels of
      oxysterol binding protein mRNA affected by 1 microM 25-hydroxycholesterol.
      Furthermore, both cells express the cellular nucleic acid binding protein (CNBP),
      a 7 zinc finger, DNA-binding protein of unknown function, regulated by
      oxysterols. The levels of CNBP mRNA are significantly reduced by 25
      hydroxycholesterol in the sensitive CEM C7 cells, in which the dose response and
      time course are consistent with occupancy of the oxysterol binding protein by
      oxysterol and with subsequent cell kill. However, in the resistant M10 cells,
      CNBP mRNA levels are unaffected by these concentrations of the 25
      hydroxycholesterol. Our results suggest a role for CNBP in oxysterol-induced
      regulation of cell viability and growth.

PMID- 8142310
TI  - Nuclear extracts enhance the interaction of fusion proteins containing the DNA
      binding domain of the androgen and glucocorticoid receptor with androgen and
      glucocorticoid response elements.
AB  - Comparable fragments of the androgen receptor (AR) (amino acids 540-607) and of
      the glucocorticoid receptor (GR) (amino acids 412-515) were expressed in E. coli
      as fusion proteins with protein A. Both fusion proteins, denoted ARF1 and GRF1,
      contain the DNA-binding domain and some flanking amino acids. In vitro binding
      assays have shown that both fusion proteins interact with androgen/glucocorticoid
      response elements (ARE/GREs) in an intron fragment of the C3(1) gene of the
      androgen-regulated rat prostatic binding protein and in the typically
      glucocorticoid-responsive long terminal repeat (LTR) promoter of mouse mammary
      tumour virus. Present results indicate that the interaction of both ARF1 and GRF1
      with the C3(1) as well as the LTR fragments is enhanced in the presence of
      nuclear extract. The factor that gives rise to this enhancement appears to be
      ubiquitous and sensitive to trypsin and temperature treatment. In the C3(1)
      fragment, the enhancing effect requires the presence of an intact functional
      ARE/GRE (Core II) as well as a region spanning the ARE/GRE half-site Core I.

PMID- 8142311
TI  - Estradiol-induced down-regulation of estrogen receptor. Effect of various
      modulators of protein synthesis and expression.
AB  - Incubation of MCF-7 cells with estradiol (E2) down-regulates estrogen receptor
      (ER) resulting in a progressive reduction of the capacity of cells to concentrate
      selectively [3H]E2. Scatchard plot analysis failed to detect any transformation
      of residual receptors into peptides of lower binding affinity. [3H]Estrone gave
      an identical ER disappearance pattern with an ER half-life comprised between 2
      and 3 h. A similar value was established by incubating the cells with
      [3H]tamoxifenaziridine ([3H]TAZ) for 1 h before the addition of excessive
      unlabeled E2 which induced ER-down regulation and impeded any further labeling of
      the residual receptors. Submission of the [3H]TAZ labeled cell extracts to SDS
      PAGE revealed no progressive emergence of low molecular weight cleavage products
      of the receptor (< 67 kDa). Two inhibitors of protein kinases, H-7 at 40 microM
      and H-89 at 20 microM, failed to block the E2-induced ER down-regulation. On the
      contrary, the protein phosphatases 1 and 2A inhibitor, okadaic acid, was
      effective with concentrations higher than 0.1 microM indicating that a
      dephosphorylation mechanism was involved in this phenomenon. Cycloheximide (CHX)
      also significantly reduced the receptor decrease at concentrations higher than 1
      microM. G-C specific intercalating agents [actinomycin D (AMD) and chromomycin A3
      at 1 microM] also prevented ER disappearance; ethidium bromide (EB) and
      quinacrine were ineffective. AMD and CHX operated immediately after their
      addition to the medium indicating an inhibitory action on the synthesis of an RNA
      and/or a peptide with high turnover rate involved in ER decline. Moreover, AMD
      produced its suppressive effects under conditions impeding any labeling of newly
      synthetized receptors (i.e. [3H]TAZ with an excess of unlabeled E2) rejecting the
      possibility of an increasing ER production which may partially hamper its
      disappearance. Finally, E2-induced ER mRNA down-regulation was similarly
      abolished by AMD while EB and CHX were devoid of effect.

PMID- 8142312
TI  - Inhibition of the activity of 'basic' 5 alpha-reductase (type 1) detected in DU
      145 cells and expressed in insect cells.
AB  - The purpose of this study was 2-fold: (1) to identify the 5 alpha-reductase (5
      alpha-R) isozyme(s) present in DU 145 cells, a human cell-line of low androgen
      sensitivity derived from a cerebral metastasis of an epithelial prostate cancer;
      and (2) to compare the inhibitory potencies of three compounds on the 'basic' 5
      alpha-R isozyme expressed in a baculovirus-directed insect cell system.
      Conversion of testosterone (T) into 5 alpha-dihydrotestosterone (DHT) in DU 145
      cells was measured by HPLC coupled to a Flo-one HP radioactivity detector. DU 145
      cells exhibited 5 alpha-R activity (21 pmol DHT/min/mg protein) at pH 7.4 which
      disappeared at pH 5.5 suggesting that, of the two genomically distinct human
      isozymes identified so far, type 1 5 alpha-R is expressed in DU 145 cells. This
      was confirmed by at least two observations: first, 5 alpha-R activity in DU 145
      cells was inhibited with much higher potency by 4-MA than by finasteride which is
      known to be a very poor competitor of the 'basic' enzyme (IC50s = 2.8 +/- 0.2 and
      264 +/- 55 nM, respectively). Second, only the type 1 5 alpha-R cDNA and not type
      2 5 alpha-R cDNA hybridized with DU 145 RNA. A high potency differential was also
      recorded for the inhibition of 'basic' type 1 5 alpha-R expressed in a
      baculovirus-directed-insect cell system by these two compounds, 4-MA being
      considerably more active than finasteride (Ki = 8.4 +/- 2.3 and 330 +/- 9 nM,
      respectively). This inhibition was competitive. On the other hand, inhibition by
      an n-hexane lipid/sterol extract of Serenoa repens (LSESr) was non-competitive
      and, when expressed in terms of recommended therapeutic doses, was 3-fold greater
      for LSESr than for finasteride. These studies suggest that LSESr might exert a
      regulatory inhibitory activity due to its specific lipid/sterol composition.

PMID- 8142313
TI  - Selective deletions in the 90 kDa heat shock protein (hsp90) impede hetero
      oligomeric complex formation with the glucocorticosteroid receptor (GR) or
      hormone binding by GR.
AB  - We have developed an in vivo system using coexpression of human
      glucocorticosteroid receptor (hGR) and chick hsp90 alpha (chsp90) in recombinant
      virus-infected Sf9 cells to study the formation of hetero-oligomeric complexes.
      We detected, in the cytosol, hGR complexes containing chsp90 as shown by the
      displacement of the [3H]triamcinolone acetonide bound hGR "8S" peak on
      glycerol/sucrose gradients by specific antibodies directed against chsp90 (BF4
      and D7 alpha). We took advantage of this system and of the immunoadsorption of
      hGR containing complexes with anti-hGR antibody to analyze the effect of
      deletions introduced into the hsp90 molecule on the formation of complexes with
      the hGR. Deletion of the hydrophilic region "A", between amino-acids 221 and 290,
      abolished the formation of hGR/chsp90 complexes. Deletion of the hydrophilic
      region "B" (between amino-acids 530 and 581) or deletion of a leucine repeat
      region "Z" in the middle of the molecule (amino-acids 392 to 419) still allowed
      formation of hetero-oligomeric complexes detected by immunoadsorption but the hGR
      complexes formed with mutated chsp90s were devoid of steroid binding properties.
      These results are consistent with (1) the possible involvement of the "A" region
      in the interaction of hsp90 with steroid receptors and (2) a role of B and Z
      regions in the hsp90 structure for maintaining the steroid binding property of
      the hGR.

PMID- 8142314
TI  - Steroid sulfation by expressed human cytosolic sulfotransferases.
AB  - The human cytosolic sulfotransferases (STs), dehydroepiandrosterone
      sulfotransferase (DHEA-ST) and the phenol-sulfating form of phenol
      sulfotransferase, (P-PST), have been expressed in bacteria and used to
      investigate the ability of the cloned enzymes to conjugate steroids and related
      compounds. DHEA-ST was capable of sulfating all of the 3-hydroxysteroids,
      testosterone and estrogens tested as substrates. The 3-hydroxysteroids,
      androsterone, epiandrosterone and androstenediol, were conjugated at 50-60% of
      the rate of DHEA. Of the steroids tested, P-PST was capable of conjugating only
      the estrogens. The catechol estrogens, 2-hydroxyestradiol, 4-hydroxyestradiol and
      4-hydroxyestrone, and compounds with estrogenic activity such as 17 alpha-ethynyl
      estradiol and trans-4-hydroxytamoxifen, were also tested as substrates. DHEA-ST
      showed little or no sulfation activity with these compounds; however, all of
      these compounds were sulfated by P-PST. These results indicate that the expressed
      human STs are valuable in analyzing the overlapping substrate specificities of
      these enzymes and that P-PST may have an important role in the metabolism of
      estrogens and estrogenic compounds in human tissues.

PMID- 8142315
TI  - Enhanced stimulation of 5 alpha-reductase activity in cultured Leydig cell
      precursors by human chorionic gonadotropin.
AB  - Previous studies have demonstrated that the increase in number of Leydig cells
      during prepubertal maturation results, in part, from the differentiation of
      mesenchymal precursors between the second and fourth week of postnatal life.
      After conversion to immature Leydig cells, they actively synthesize testosterone,
      but this androgen does not accumulate because high 5 alpha-reductase activity
      rapidly converts testosterone to 5 alpha-reduced metabolites. The present studies
      examined whether the conversion of precursor cells to immature Leydig cells in
      vitro by human chorionic gonadotropin (hCG), as characterized by progressive
      increases in testosterone formation and 5-ene-3 beta-hydroxysteroid dehydrogenase
      isomerase (3 beta-HSD) activity, is associated similarly with an enhanced
      stimulation of 5 alpha-reductase activity. We also evaluated whether this
      conversion occurs following blockade of dihydrotestosterone (DHT) formation by
      the inclusion of a 5 alpha-reductase inhibitor during the entire treatment
      period. Precursor cells were isolated from immature rats using a multi-step
      procedure normally used to isolate highly purified Leydig cells from adult or
      immature rats. These cells localize in a region of lower density on Percoll
      gradients than Leydig cells. Although the acute (3h) response to hCG with respect
      to testosterone formation, and basal 3 beta-HSD and 5 alpha-reductase activities
      on day 1 of culture were much higher in purified Leydig cells than precursor
      cells from immature rats, the response of each parameter to chronic (6-day)
      treatment with hCG was much greater in precursor cells. Furthermore, the
      conversion of precursor cells to immature Leydig cells occurred in the presence
      of a 5 alpha-reductase inhibitor during the entire treatment period, suggesting
      that this conversion occurs in the absence of DHT. These results demonstrate for
      the first time that in addition to increased testosterone biosynthesis and 3 beta
      HSD activity, the conversion of precursor cells to immature Leydig cells, in
      vitro, in response to chronic hCG treatment, involves enhanced 5 alpha-reductase
      activity.

PMID- 8142316
TI  - Mifepristone treatment demonstrates the participation of adrenal glucocorticoids
      in the regulation of oestrogen-induced prolactin secretion in ovariectomized
      rats.
AB  - Accumulated evidence indicates that the adrenal cortex is able to regulate
      prolactin (PRL) secretion in rats. The aim of this study was to determine the
      participation of adrenal steroids on the regulation of PRL release in
      ovariectomized (OVX) and oestrogen-treated rats, by using mifepristone or a
      specific progesterone antiserum. Blood samples were obtained at 13:00 and 18:00 h
      3 days after priming with oestradiol benzoate (OB). A significant increase in
      serum PRL at 13:00 and 18:00 h was induced by OB treatment. The administration of
      mifepristone to OVX and oestrogen-primed rats enhanced serum PRL increase at
      13:00 h, without modifying the values at 18:00 h; while the administration of
      progesterone antiserum did not modify PRL levels, indicating that the effect of
      mifepristone on PRL secretion is due to its antiglucocorticoid action.
      Adrenalectomy induced a release of PRL at 13:00 h similar to that observed in the
      OVX and oestrogen-primed rats after mifepristone administration. Treatment with a
      low dose of progesterone (0.1 mg/rat) to OVX, adrenalectomized and oestrogen
      primed rats did not modify the effect of adrenalectomy in serum PRL. Progesterone
      (2 mg/rat) given at 08:00 h to OVX and oestrogen-primed rats increased serum PRL
      5 h later. Mifepristone treatment partially reverted the PRL increase induced by
      progesterone. These results suggest that after a previous sensitization of the
      pituitary by oestrogen, circulating glucocorticoids may exert a direct inhibitory
      effect on PRL release. This inhibition takes place at 13:00 h on day 3. On the
      other hand, the lack of effect of mifepristone or adrenalectomy on the PRL
      release at 18:00 h may also indicate that neither progesterone nor
      glucocorticoids modify PRL release induced by oestrogen at this time.

PMID- 8142317
TI  - Steroids and opioid receptors.
AB  - The genomic mode of action is believed to represent the predominant effect of a
      steroid hormone. Recently, however, rapidly manifesting, non-genomic effects have
      also been observed. These are mediated mostly by allosteric interaction of a
      steroid with heterologous target structures such as membrane receptors, a
      prototype example being the GABAA. Here we describe our studies considering two
      interdependent questions: (1) do steroids also interact with opioid receptors in
      brain? Twenty different steroids, i.e. estrogens, androgens, glucocorticoids,
      mineralocorticoids, gestagens and a cardiac glycoside were tested with respect to
      their ability to compete for in vitro binding to rat brain membranes of 3H
      ligands specific for delta, mu and kappa opioid receptors, respectively. Among
      all classes of steroids, only the estrogens were effective, all others were 20 to
      100 times less effective or ineffective. The rank order among the estrogens was
      diethylstilbestrol > 17 alpha-estradiol > 17 alpha-ethinyl-estradiol > estriol >
      estrone > 17 beta-estradiol. Next potent to estrogens (although far less) were-
      on average as a group--glucocorticoids, followed by mineralocorticoids,
      androgens, gestagens and digoxin. This global as well as within-group rank order,
      was, with rare exceptions, qualitatively equal irrespective of which radioligand
      was used, yet displayed the various radioligands different sensitivities with
      respect of being inhibited by steroids (irrespective of kind), i.e. in the order
      [3H]naloxone > or = [3H]DAGO > or = [3H]DADL > [3H]DPDP >> [3H]etorphine. The
      IC50 of diethylstilbestrol for displacing [3H]DAGO was approximately 30 microM
      and that of 17 beta-estradiol was approximately 200 microM. (2) What are the
      concentrations of the major steroid hormones in the brain's extracellular fluid?
      We have analyzed in 56 matched (i.e. simultaneously withdrawn) peripheral serum
      and cerebrospinal fluid (CSF) samples (from endocrinologically grossly normal
      patients) the concentrations of the unconjugated steroid hormones testosterone,
      androstenedione, dehydroepiandrosterone (DHEA), progesterone and cortisol (all
      being more or less lipophilic) as well as those of their hydrophilic
      counterparts, i.e. DHEA-sulfate, or their hydrophilic binding proteins, i.e. sex
      hormone binding globulin, corticosterone binding globulin, and albumin. Total
      (i.e. free plus protein-bound) CSF levels of all these steroids were found to be
      in the 0.02-2 nM range except for cortisol (approximately 20-50 nM), thus 3 to 4
      orders of magnitude lower than the IC50 of estrogens for [3H]DAGO (see above).
      These total CSF values were quite similar to the reported and calculated free
      serum levels of these steroids and no difference existed between those of
      patients with intact or with disturbed (abnormally leaky) blood-brain barrier
      function.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8142318
TI  - Androgen binding sites in peripheral human mononuclear leukocytes of healthy
      males and females.
AB  - Androgen binding sites have been identified in circulating human mononuclear
      leukocytes of healthy donors of both sexes. Cells were separated from blood
      samples on a Ficoll gradient and incubated with different concentrations of
      [3H]testosterone in the presence or absence of a 400-fold excess of unlabelled
      testosterone. Binding data were derived from Scatchard analysis. The binding
      sites fulfil the required criteria for specific steroid binding sites however
      differ somewhat from the classic androgen receptors from genital skin fibroblast:
      in fertile adult males (n = 20) the binding sites showed (1) a high affinity for
      testosterone (1.32 +/- 0.49 nM; mean +/- SD), (2) a saturable capacity (184 +/-
      52 binding sites per cell; mean +/- SD), and (3) a characteristic competitive
      binding profile for other steroid hormones (relative binding affinities:
      testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone, whereas
      aldosterone, 17-hydroxy-progesterone and cortisol did not compete appreciably).
      Furthermore the number of binding sites determined using [3H]dihydrotestosterone,
      [3H]RU-1881, or [3H]testosterone were comparable. This raises the possibility
      that androgen receptors in peripheral mononuclear leukocytes differ from those in
      genital skin fibroblasts. There was no apparent correlation between serum
      testosterone concentrations and androgen binding sites. In fertile women
      remarkable changes in androgen binding sites were seen in the course of the
      menstrual cycle, with a significant increase in the immediate preovulatory
      period. The presence of androgen receptors in peripheral mononuclear leukocytes
      provides for the first time the experimental basis for an hypothesis of direct,
      receptor-mediated effects of androgens on mature immunocompetent cells. The
      immunological implications of these results are discussed.

PMID- 8142319
TI  - Comparison of 16-androstene steroid concentrations in sterile apocrine sweat and
      axillary secretions: interconversions of 16-androstenes by the axillary
      microflora--a mechanism for axillary odour production in man?
AB  - The concentrations of five 16-androstene steroids were determined, by a GC-MS
      method, in freshly-produced apocrine sweat (adrenaline-induced), in 8 men and 2
      women. The ranges of concentrations (nmol/microliter) in apocrine sweat were: 5
      alpha-androst-16-en-3-one (5 alpha-A), 0.1-2.0 and 4,16-androstadien-3-one
      (androstadienone), 0-1.9, 5,16-Androstadien-3 beta-ol (androstadienol) was also
      found in 5 of the subjects (range 0.05-1.05). 5 alpha-Androst-16-en-3 alpha- or 3
      beta-ols [3 alpha (beta)-androstenols] were only found in small amounts (< 0.1
      nmol/microliters) in a few subjects. In the second study, prior to apocrine sweat
      collection (adrenaline injection), the axillary skin of 6 of the male subjects
      was washed with diethyl ether on an adjacent site of the axillary vault. The
      concentrations of 16-androstenes were compared in the ethereal extracts and
      apocrine sweat. The former contained detectable levels (pmol/cm2) of
      androstadienone (17.9 +/- 2.4), 3 alpha-androstenol (6.9 +/- 3.7), 3 beta
      androstenol (1.8 +/- 1.0) and androstadienol (1.9 +/- 0.5) (means +/- SEM) in all
      6 subjects. All but 1 subject also had 5 alpha-androstenone, the mean value for
      the others being 2.5 +/- 0.6. The axillary skin levels of 3 alpha- and 3 beta
      androstenols, androstadienol and, in 3 subjects, androstadienone exceeded those
      in the apocrine sweat obtained from the same subjects, whereas levels of 5 alpha
      androstenone in the skin extracts were all lower than in apocrine sweat samples,
      when related to the corresponding areas of skin sampled. The metabolism of 16
      androstenes was studied in vitro in the presence of two aerobic coryneform
      bacteria, previously shown to metabolize testosterone as well as being capable of
      producing odour from extracts of axillary sweat in an odour-generation test.
      Although both coryneforms caused complex metabolic reactions and were capable of
      oxidation or reduction at C-3 and C-4, the overall direction favoured reduction.
      For example, large quantities of the more odorous 5 alpha-androstenone and 3
      alpha-androstenol were formed from androstadienol and androstadienone. In
      contrast, strains of corynebacteria, unable to produce odour and incapable of
      metabolizing testosterone, were also unable to metabolize 16
      androstenes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8142320
TI  - Balancing the extraction of primary teeth: a review.
AB  - Balancing the extraction of primary teeth is a procedure advocated to maintain
      symmetry of the developing dentition by encouraging symmetrical drift of teeth
      mesial and distal to the extraction sites on each side of the dental arch.
      Current opinion about this procedure expressed in standard reference works is
      confused and occasionally contradictory. Whilst some authorities cite specific
      situations where balancing extractions should be performed, others are less
      precise with their advice, and at least one considers that there is little
      justification for the procedure. Scientific evidence supporting the procedure is
      tenuous. The one study carried out specifically to compare dental centre line
      shift following unilateral or bilateral extraction of primary teeth showed
      greater shift in cases of unilateral (unbalanced) extractions. Other studies do
      not directly address the issue and such information as they offer is imprecise.
      Although the procedure of balancing extractions is strongly advocated by many
      clinicians, it is not based on definitive experimental evidence.

PMID- 8142321
TI  - Dental health of 12-year-old children living in similar rural communities in
      France and England.
AB  - A survey was conducted of the dental health of 12-year-old children attending
      state schools in the towns of Segre (France) and Shaftesbury (England). The
      results showed that the Segre children had DMFT and DMFS scores double that of
      the Shaftesbury children. More Segre children had calculus and more were
      undergoing orthodontic treatment. There were no significant differences between
      the two schools in gingival health and oral cleanliness, but in both the French
      and English schools the girls had cleaner teeth than the boys.

PMID- 8142322
TI  - The Dental Fear Survey Schedule: a study with Finnish children.
AB  - The reliability and validity of the Dental Fear Survey Schedule for Children
      (DFSS-C) was examined in a sample of 828 school children in Finland. The DFSS-C
      mean was 22.1. Choking, injections and drilling were the most common fears.
      Internal consistency indicated a high level of reliability. Factor analysis
      (principal components, varimax rotation) found three factors accounting for 54%
      of the scale variance. Factors were defined as (1) fear of highly invasive
      procedures, such as injections and drilling; (2) fear of potential victimization,
      including fear of strangers, choking and hospitals; and (3) fear of less invasive
      procedures, such as opening the mouth and being examined by the dentist. The
      factor pattern was similar to results obtained with a sample of children in the
      United States. There were significant differences in fear score for children
      whose parents reported them fearful and/or reported them to have had a previous
      bad experience at the dentist. Boys (but not girls) who had a DMFT score of at
      least 1 had a significantly higher mean DFSS-C score (21.1) than those who were
      caries free (20.0). These data suggest the DFSS-C operates in Finland as it does
      in the United States, but that culture-specific minimal scores for determining
      high dental fear are needed.

PMID- 8142323
TI  - Influence of wearing latex gloves on electric pulp tester readings in children.
AB  - Electric pulp testers operated by completing an electric circuit. Latex
      examination gloves have been claimed to interrupt this circuit and lead to false
      negative results. This study was conducted to evaluate the influence of wearing
      latex gloves on electric pulp tester (EPT) readings. The pulps of 80 maxillary
      permanent incisors of 22 children 10-13 1/2 years old were tested using the
      Pelton & Crane 'Vitapulp' instrument. Each tooth was tested twice: with gloves
      and with bare hands. Teeth failing to respond to the EPT without gloves were
      excluded from the study. All EPT readings ranged between 1 and 9.5. Five teeth
      gave the same responses with gloved and ungloved hands. Only five teeth did not
      respond when gloves were worn, and all of these gave readings near the top of the
      EPT scale when tested without gloves. The other 70 teeth presented significantly
      higher readings with gloves than without gloves. It is concluded that removal of
      examination gloves during the operation of the EPT is necessary only if no
      response is obtained.

PMID- 8142324
TI  - Late development of supernumerary teeth: a report of two cases.
AB  - Two cases are presented of late developing supernumerary teeth. In the first the
      patient developed two crops of supernumeraries, both of which were found on
      radiographic examination following delay in the normal eruption pattern of the
      permanent dentition. The first crop of four supernumerary teeth were in the
      maxillary incisor region and were surgically removed; 5 years later four more
      supernumerary teeth was found in the maxillary canine and mandibular premolar
      regions, which were also surgically extracted. In the second case two
      supplemental mandibular premolars were found as an incidental finding on
      radiographic examination at the age of 15 years following orthodontic treatment,
      the patient having previously had four first premolars extracted; these
      supernumerary teeth were not extracted as they were asymptomatic. These cases
      emphasize the importance of careful review of patients with a history of
      supernumerary teeth and, where clinically indicated, of further radiographic
      examination.

PMID- 8142325
TI  - An unusual hypoplastic premolar: a case report.
AB  - This case report describes an unusual hypoplastic maxillary first premolar tooth
      that was diagnosed radiographically in a 10-year-old boy. The maxillary primary
      first molar had been extracted. When the tooth erupted the hypoplasia was seen to
      be confined to the mesial aspect of the tooth. The cause of this unusual
      distribution was considered to be either infection associated with the
      mesiobuccal root of the primary first molar or trauma during extraction of the
      primary tooth. The tooth was restored using dentine adhesive and posterior
      composite material.

PMID- 8142326
TI  - Operation Belarus: an enquiry into the status of paediatric dentistry.

PMID- 8142327
TI  - Forage and splanchnic tissue mass in growing lambs: effects of dietary forage
      levels and source on splanchnic tissue mass in growing lambs.
AB  - Forty-two crossbred lambs (33.4 kg initial body weight; twenty-four wethers and
      eighteen ewes) were used in a 42 d experiment with a 2 x 3 factorial treatment
      arrangement to determine effects of forage level and source on splanchnic tissue
      mass. Diets were 250 and 750 g/kg of chopped lucerne (Medicago sativa) (A),
      ryegrass (Lolium multiflorum)-wheat (Triticum aestivum) (RW) or bermudagrass
      (Cynodon dactylon) (B) hay, with the remainder being maize-based concentrate.
      Five lambs per treatment were slaughtered at the end of the experiment and
      measurements made of internal organs and contents of the gastrointestinal tract
      (GIT). Digestible organic matter intake (DOMI) on the 7 d preceding slaughter was
      0.89, 0.83, 0.90, 0.83, 0.77 and 0.61 (SE 0.05) kg/d, and live-weight gain was
      0.20, 0.17, 0.18, 0.10, 0.10 and 0.07 (SE 0.02) kg/d for diets A-25, RW-25, B-25,
      A-75, RW-75 and B-75 respectively. Total GIT mass (fresh) was higher (P < 0.05)
      for 750 than 250 g forage/kg and for B than RW (4.80, 4.57, 5.55, 5.84, 5.99 and
      6.91 kg for diets A-25, RW-25, B-25, A-75, RW-75 and B-75 respectively). Non-fat
      organic matter was 259, 295, 292, 303, 277 and 264 g for the total GIT; 93, 102,
      103, 106, 95 and 97 g for the reticulo-rumen (forage level x type (diet A v.
      diets RW and B) interaction; P < 0.05); and 204, 196, 202, 177, 156 and 127 g for
      the liver (SE 10) with diets A-25, RW-25, B-25, A-75, RW-75 and B-75
      respectively. In summary, differences in properties of forage A and the grasses
      at 250 g/kg diet may have influenced GIT mass independent of energy intake and
      digesta mass. Conversely, with 750 g dietary forage/kg, higher digesta mass for
      diet B than diet RW appeared responsible for high reticulo-rumen mass relative to
      DOMI. Greater digesta mass for 750 than 250 g forage/kg may have elevated
      intestinal tissue mass/DOMI with diets A and B but not with diet RW, for which
      NDF digestibility was highest.

PMID- 8142328
TI  - Osmotic pressure, water kinetics and volatile fatty acid absorption in the rumen
      of sheep sustained by intragastric infusions.
AB  - The effects of changing rumen osmotic pressure (OP) upon water kinetics and
      volatile fatty acid (VFA) absorption in the rumen of sheep were studied in two 4
      x 4 Latin square experiments, each using four lambs with a rumen cannula and an
      abomasal catheter. In both experiments the lambs were sustained by the
      intragastric infusion of all nutrients (VFA, Ca, P, Mg and a buffer solution into
      the rumen, and casein, vitamins and trace elements into the abomasum). On
      experimental days, which were at least 1 week apart, drinking water and the
      casein infusion were withdrawn, and the ruminal OP was changed and held constant
      for 9.5 h, by incorporating NaCl at different concentrations in the buffer
      solution being infused. In Expt 1 the target OP values were 300, 340, 380 and 420
      mosmol/kg, and in Expt 2 were 261 (no saline addition), 350, 420 and 490
      mosmol/kg. Using soluble non-absorbable markers (PEG in continuous infusion and
      Cr-EDTA injected in pulse doses) rumen volume, liquid outflow rates, apparent
      water absorption through the rumen wall and VFA absorption rates were estimated
      at six sampling times corresponding to the 1.5 h intervals during the last 7.5 h
      following the change in rumen OP. Liquid outflow rate (F; ml/h) showed a
      significant and positive linear relationship with the rumen OP (mosmol/kg),
      resulting in the equation F = 1.24 OP (SE 0.096)-36.5 (SE 36.6) (r2 0.96).
      Similarly, water absorption rate (W; ml/h) was significantly affected by rumen
      OP, and this relationship was given by W = 395 (SE 39.9)-1.16 OP (SE 0.105) (r2
      0.95), which means that for an OP of 341 mosmol/kg the net movement of water
      across the rumen wall would be zero, and either a net efflux or a net influx of
      water would be observed with lower or higher OP respectively. In Expt 2 there was
      a significant linear effect of OP on rumen volume (P < 0.01), with higher OP
      being associated with increases in rumen liquid contents of about 10-20%. As
      rumen OP was increased there was also a decline in the absorption rate of VFA
      (from 232 mmol VFA/h for OP 350 to 191 mmol/h for OP 490 mosmol/kg), resulting in
      the accumulation of VFA (especially acetate) in the rumen and a consequent fall
      in rumen pH. Rumen OP seems to be important in defining water movement across the
      rumen wall and, hence, partitioning between absorption and outflow.

PMID- 8142329
TI  - Intestinal nitrogen and electrolyte movements following fermented milk ingestion
      in man.
AB  - The present study focuses on the digestion and absorption of milk and fermented
      milk (FM) reflected by gastro-ileal N and electrolyte movements in six healthy
      volunteers. The N and electrolyte content of the intestinal effluents were
      analysed both at the beginning of the jejunum and in the distal ileum. The
      gastric half-emptying time of the liquid phase was significantly (P < 0.05)
      shorter for milk (35 (SE 2) min) than for FM (60 (SE 2) min). The N balance
      showed that 58 and 50% of ingested proteins, milk and FM respectively were
      absorbed between the stomach and the proximal jejunum and that 91 and 90%
      respectively were absorbed between the stomach and the terminal ileum in 240 min.
      Evaluation of mineral absorption indicated that 44 and 67% of Ca was absorbed in
      the duodenum after milk and FM ingestion respectively, and 41 and 11% of Ca
      disappeared between the jejunum and the ileum respectively. With regards to N and
      Ca intestinal availability, the present study confirms that FM products represent
      an interesting source of N as well as minerals for man. This confers on FM a
      beneficial effect compared with milk especially for lactase (EC 3.2.1.108)
      deficient subjects and children with persistent diarrhoea.

PMID- 8142330
TI  - A study on lipid metabolism in heart and liver of cholesterol- and pectin-fed
      rats.
AB  - Pectin is known as a cholesterol-reducing dietary fibre, and in the present study
      we addressed the question whether pectin affected the quantity of lipid in
      droplets in the myocardial cells and of lipid in the liver cells. Male Wistar
      rats received either a diet containing cholesterol or a standard diet without
      cholesterol with 0, 50 or 100 g pectin/kg incorporated for 10 d. The fractional
      volume of lipid droplets in the myocardial cells decreased as a function of
      pectin dose in both the standard-fed and the cholesterol-fed rats. Serum
      cholesterol was significantly reduced in both groups after addition of 100 g
      pectin/kg diet. The cholesterol diet increased the liver cholesterol level, and
      100 g pectin/kg diet resulted in a lower concentration of liver cholesterol in
      the cholesterol-fed animals, but the influence on standard-fed rats was modest.
      Hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88; HMG-CoA reductase) activity
      increased when pectin was given in the standard diet. Liver triacylglycerol level
      increased after cholesterol and pectin feeding. Mitochondrial fatty acid
      oxidation and phosphatidate phosphohydrolase (EC 3.1.3.4) activity tended to
      decrease, whereas the peroxisomal fatty acid oxidation and acyl-CoA oxidase
      activity were unchanged. Increased hepatic triacylglycerol content by cholesterol
      and pectin treatment may be due to inhibited mitochondrial fatty acid oxidation
      along with increased availability of fatty acid for esterification and
      triacylglycerol synthesis. The presence of pectin in the diets of cholesterol-fed
      rats resulted in increased hepatic concentration of triacylglycerols and
      increased mitochondrial fatty acid oxidation. In this case the hepatic
      accumulation of triacylglycerol may be mediated by a reduced efflux of
      triacylglycerols from the liver.

PMID- 8142331
TI  - The effect of dietary lipid changes on the fatty acid composition and function of
      liver, heart and brain mitochondria in the rat at different ages.
AB  - A correlation between dietary lipids and cellular enzyme activities is a problem
      that has only been partially addressed by nutritionists. Therefore, changes in
      the fatty acid composition and the activities of some key metabolic enzymes
      (ubiquinol-2-cytochrome c reductase (EC 1.10.2.2), cytochrome oxidase (EC
      1.9.3.1) and ATPase (EC 3.6.1.3)) in the mitochondria of liver, heart and brain
      of rats fed on diets differing extensively in their polyunsaturated fatty acid
      compositions have been investigated. The results showed that fatty acid
      compositional changes brought about by the dietary differences were associated
      with extensive changes in the activities of these key enzymes in the
      mitochondria. The extent of the influence differed considerably with the period
      over which the diets were fed. The role of dietary lipids to effect changes
      through the preservation of membrane structural integrity is discussed.

PMID- 8142332
TI  - Absorption of iron from ferric hydroxypyranone complexes.
AB  - The absorption of 59Fe from preparations of FeSO4 and the ferric hydroxypyranone
      complexes maltol and ethyl maltol was studied by whole-body counting in normal
      subjects and patients with Fe deficiency. Fe in the Fe3+ complexes was in general
      absorbed almost as well as Fe2+. It is concluded that the absorption of Fe3+ from
      hydroxypyranone complexes is much greater than that from simple Fe3+ salts; this
      may prove an efficient and less toxic form of Fe for the treatment of deficiency.

PMID- 8142333
TI  - Diurnal changes in large-bowel metabolism: short-chain fatty acids and transit
      time in rats fed on wheat bran.
AB  - To investigate diurnal changes in large-bowel metabolism rats were fed once daily
      on a cooked maize-based diet without or with 200 g wheat bran/kg diet and
      containing Cr2O3 as an indigestible marker. After 17 d four rats on each diet
      were killed at 4, 10, 16 and 22 h postfeeding. Emptying of dry matter (DM) from
      the stomach occurred by an apparently zero-order process at about 0.5 g/h in both
      diet groups. Feeding wheat bran had little effect on caecal pH or total short
      chain fatty acid (SCFA) concentration but was associated with a marked increase
      in molar proportion of butyrate and a fall in propionate. There were substantial
      changes in caecal total SCFA concentration and in the molar proportions of
      individual SCFA throughout the day but no evidence of an interaction between diet
      and time interval after feeding. Caecal transit time (TT) was significantly
      reduced by feeding wheat bran whilst colonic TT was unaffected. Although when
      averaged across both diets there were no significant time effects on caecal or
      colonic TT, there was a significant diet x time interaction for caecal TT. The
      extent of coprophagy was measured. The proportion of stomach DM derived from
      ingested faeces increased with time interval after feeding but it was always a
      minor contribution so that in these circumstances coprophagy is unlikely to
      result in significant bias in estimates of digesta flow-rates or TT.

PMID- 8142334
TI  - The immunological and long-term atopic outcome of infants born to women following
      a milk-free diet during late pregnancy and lactation: a pilot study.
AB  - Infants born to atopic parents have been found to be at high risk of allergy
      development. The present study investigated the effect of a maternal milk-free
      diet during late pregnancy and lactation on the immune response and allergy
      incidence in at-risk and control infants. Atopic mothers were randomly allocated
      into an intervention group (n 12) or an unrestricted-diet group (n14) and
      compared with non-atopic mothers following an unrestricted diet (n 12). The
      intervention involved a maternal milk-free diet during late pregnancy and
      lactation. Infants were followed up for 18 months postnatally. A significant fall
      in maternal serum beta-lactoglobulin (beta-Lg)-immunoglobulin G (IgG) antibody
      levels (P < 0.05) was observed after a 7-week milk-exclusion diet. In maternal
      and cord serum samples the levels of beta-Lg-IgG and alpha-casein-IgG antibodies
      were significantly correlated (r 0.89, P < 0.0001 and r 0.71, P < 0.001
      respectively). Higher levels of beta-Lg-IgG (P < 0.05) were observed in the cord
      serum samples compared with paired maternal serum samples. Single-blind allergy
      assessment by a paediatrician at 12 and 18 months showed that the infants born in
      the non-atopic group had a significantly lower allergy incidence compared with
      the infants born in the atopic group following an unrestricted diet (P < 0.008
      and P < 0.02 respectively). The allergy incidence in the infants born in the
      atopic diet group was significantly lower compared with that of the atopic group
      following an unrestricted diet (P < 0.04). It was observed that the atopic nature
      of the parents significantly affected the allergy incidence in their children. A
      trend towards a beneficial effect of a maternal milk-free diet during late
      pregnancy and lactation was also observed in infants born to atopic parents.

PMID- 8142336
TI  - Dietary indices of atherogenicity and thrombogenicity and ischaemic heart disease
      risk: the Caerphilly Prospective Study.
AB  - The aim of the study was to investigate whether proposed dietary scores of
      atherogenicity and thrombogenicity predict ischaemic heart disease (IHD) risk in
      a community sample of men aged 45-59 years. Dietary scores were calculated from
      consumption of various fatty acids, estimated from 7 d weighed intake data
      obtained from 665 men. Investigation of associations with blood lipids,
      lipoproteins and haemostatic factors revealed positive associations with low
      density-lipoprotein cholesterol (P < 0.05) and white cell count (P < 0.05), and a
      negative association with antithrombin III (P = 0.05), after taking into account
      the effects of age, body mass index and smoking. During a 5-year follow-up
      period, there were twenty-one new IHD events among the 512 men in whom there was
      no evidence of IHD at baseline. Men with higher atherogenicity or thrombogenicity
      scores at baseline tended to have a higher risk of subsequent IHD. The trend was
      consistent but not statistically significant. A similar trend was observed for
      total saturates, and an inverse trend for total polyunsaturates, expressed as a
      percentage of total fatty acids. It is, therefore, concluded that proposed
      dietary indices of atherogenicity and thrombogenicity may be weak predictors of
      IHD risk, but that these scores are unlikely to be substantially better
      predictors than more simple approaches such as intakes of total saturates. To
      enhance the predictive ability, more complex formulas which take into account
      other dietary factors as well as fatty acid intakes would probably be required.

PMID- 8142335
TI  - Level of nutrition and age at weaning: effects on humoral immunity in young
      calves.
AB  - Thirty-two calves were studied to determine the effects of level of nutrition
      (400 and 1000 g (air-dry matter) milk substitute per d) and age at weaning (5, 9
      and 13 weeks) on humoral immune responses measured in serum and bronchoalveolar
      washings (BAW). All calves were immunized with Keyhole limpet haemocyanin (KLH)
      at 3 weeks of age, and with horse erythrocytes (HRBC) 1 d after weaning. Feeding
      the higher level of nutrition compared with the lower level decreased anti-HRBC
      titres and serum IgG2 and IgA responses to KLH (P < 0.05). Weaning at 5 compared
      with 9 weeks of age decreased serum anti-HRBC responses (P < 0.05), but weaning
      age had no effect on anti-KLH responses (P > 0.05). Feeding the higher level of
      nutrition increased total protein (P < 0.05) and IgG2 concentrations (P < 0.01)
      in BAW. The results showed that variation in husbandry conditions that is within
      conventional limits affects humoral immune responses in young, artificially
      reared calves.

PMID- 8142337
TI  - Parental death from cardiovascular disease and dietary habits in an elderly
      group.
AB  - The present study examines the influence of parental history of death from
      cardiovascular disease on dietary habits and nutritional status of a group of
      seventy-two Spanish elderly. Those with at least one parent who had died of
      cardiovascular disease (43.1% of the cases) had higher diastolic blood pressure
      (P < 0.05) and nutrient intakes less favourable from the cardiovascular risk
      point of view than those whose parents died of other causes. Descendants whose
      parents died of cardiovascular disease had higher total fat, animal fat,
      saturated fatty acids, myristic acid and palmitic acid intakes and a lower
      monounsaturated fatty acids:saturated fatty acids value than descendants of those
      who died from other causes (all P < 0.05).

PMID- 8142338
TI  - Determinants of plasma cholesterol responsiveness to diet.
AB  - Plasma cholesterol change, or 'responsiveness', to dietary saturated fat
      modification has long been acknowledged. The present study sought to determine
      the specific, predicted response of each cholesterol subfraction to known dietary
      manipulations. Two metabolically controlled diets, one with a low
      polyunsaturated:saturated fat (low P:S) ratio, and one with a high P:S ratio were
      fed in a crossover design to sixty-seven normolipidaemic subjects pooled from six
      foregoing metabolic studies. A series of statistical analyses was performed to
      identify the lipids and subfractions independently affected by the diet
      crossover. Multivariate analysis of variance revealed that the changes in total
      cholesterol (delta TC), low-density-lipoprotein-cholesterol (delta LDL-C), and
      high-density-lipoprotein-cholesterol (delta HDL-C) were the only statistically
      significant diet-specific 'responsive' lipids. Multiple regression was performed
      to identify the independent predictors of delta TC, delta LDL-C and delta HDL-C.
      It was found that age (years), extent of change in dietary saturated fat, and
      baseline LDL-C (mg/l) levels determine LDL-C change, while extent of change in
      saturated and polyunsaturated fat, and baseline HDL-C (mg/l) levels can predict
      HDL-C change. A series of equations to predict lipoprotein responsiveness to diet
      are derived for potential use in clinical practice.

PMID- 8142339
TI  - Dietary level of maize oil affects growth and lipid composition of Walker 256
      carcinosarcoma.
AB  - Walker 256 carcinosarcoma cells (1 x 10(4)) were injected into the right thigh
      muscle of Sprague-Dawley rats (125 g) consuming isoenergetic (200 g fat/kg) diets
      containing 20, 100 and 200 g maize oil/kg and 180, 100 or 0 g hydrogenated
      lard/kg respectively. Ten rats from each dietary regimen were killed every 4th
      day. Tumours grew rapidly from day 0 to day 8 post-transplant regardless of
      dietary regimen. However, after 8 d more tumours regressed and there were fewer
      deaths in animals fed on 200 g maize oil/kg compared with animals fed on 20 or
      100 g maize oil/kg. Linoleic acid (LA) levels were higher in phospholipids (PL)
      of growing tumours than in regressing tumours whereas arachidonic acid levels in
      PL were lower in growing tumours indicating a possible alteration in the
      desaturation and elongation of LA. Serum prostaglandin E2 levels were slightly
      lower in rats with regressing tumours than in rats with growing tumours.

PMID- 8142340
TI  - Anthropometric values in an elderly French population.
AB  - We compared anthropometric indices in samples of elderly people aged 65 years and
      over living in two French areas. The samples were divided into four age-groups
      (65-69, 70-74, 75-79 and over 80 years). We observed interregional differences in
      women aged 65-69 years and in men aged 65-74 years. Weight and anthropometric
      variables related to body fat percentage and to muscle mass showed a decline with
      age as already reported by others. We established anthropometric percentile
      values according to sex in pooled subjects when no integrated difference was
      found. The 50th percentile of arm circumference, muscle arm circumference and
      triceps skinfold was higher, and the 50th percentile of body mass index was lower
      than the one reported for the same indices from an elderly Welsh population. Our
      results show that an interregional difference in anthropometric indices exists in
      the elderly. The differences which are observed between our results and those
      reported from a British population emphasize the importance of establishing local
      values for the elderly population.

PMID- 8142341
TI  - [Epidemiology of the plague. Changes in the concept in research of infection
      chains since the discovery of the plague pathogen in 1894].
AB  - Three major plague epidemics have been recorded worldwide up to this day: the
      Justinian plague in the 6th century, the Black Death in the 14th century and the
      recent 20th century pandemic. The latter occurred at a time of advanced
      microbiological knowledge which permitted the etiology and the modes of
      transmission and spread of this bacterial infectious disease to be clarified. The
      present thesis is an attempt to describe the changes in plague research that
      occurred during that period of time. While the German, Austrian, British, Russian
      and Egyptian plague Commissions studying the Indian plague outbreak after 1896
      contributed only little to the fundamental epidemiological knowledge on plague,
      several individual researchers succeeded in discovering some of the key facts in
      the etiology and transmission of the disease. Alexandre Yersin discovered the
      pathogenic agent of plague (Hongkong 1894), E.H. Hankin, P.L. Simond (Bombay
      1898) and J.A. Thompson (Sydney 1900) recognized the role of rat plague, M. Ogata
      (Formosa 1897) and P.L. Simond (Bombay 1898) observed the transmission of the
      disease by fleas, and A.W. Bacot and C.J. Martin (1914) described the specific
      mechanism of transmission of plague. Accordingly, fleas transmit plague from rat
      to man, the efficiency of the flea as a vector depending on a blocking phenomenon
      specific of each flea species. The Indian rat flea (Xenopsylla cheopis) has been
      recognized the most efficient vector. Although the involvement of wild rodents
      was already known shortly after the turn of this century, the concept of sylvatic
      plague (the plague of wild rodents) as opposed to murine plague (the plague of
      commensal rodents) only emerged between 1920 and 1950. It led to taking stock of
      all hosts and vectors of the disease and thereby defining the natural foci of
      plague. According to this concept plague is primarily a disease of wild rodents
      which have been carrying it together with their fleas since ever. As man and
      urban rats only become infected occasionally, they do not constitute chronic
      foci. The occurrence of persistent foci rather depends on the interaction of
      resistant and sensitive wild rodents (burrowing animals) as was discovered by
      French researchers in the Middle East as late as the 1950s and 1960s. The concept
      of rodent-dependent transmission was somewhat attenuated by the discovery of
      direct interhuman transmission by French researchers between 1930 and
      1965.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8142342
TI  - A single hydrophobic to hydrophobic substitution in the transmembrane domain
      impairs aspartate receptor function.
AB  - Many transmembrane receptors, such as the insulin, EGF, and bacterial chemotaxis
      receptors, have only one or a few transmembrane domains connecting an
      extracellular ligand-binding domain to a cytoplasmic signaling domain. The
      general belief is that the transmembrane domains in these receptors have no
      specific sequence requirements as long as they are hydrophobic and long enough to
      span the membrane as an alpha-helix. To test this model, we constructed mutants
      in the aspartate receptor. This receptor is a dimer with two transmembrane
      domains per subunit. Amino acid substitutions can be made at several positions in
      the second transmembrane domain, which connects the periplasmic aspartate-binding
      domain to the cytoplasmic signaling domain, and the receptor remains functional.
      However, a single substitution of one hydrophobic residue for another can impair
      receptor function in methylation and swarm plate assays. These results suggest
      that the second transmembrane domain may pack against the other transmembrane
      domains in the receptor and small changes in this packing can affect the function
      of the receptor.

PMID- 8142343
TI  - Phosphatidylinositol-specific phospholipase C from Bacillus cereus at the lipid
      water interface: interfacial binding, catalysis, and activation.
AB  - Binding characteristics of phosphatidylinositol-specific phospholipase C (PI-PLC)
      from Bacillus cereus binding to the phospholipid-water interface were determined
      by spectroscopic methods and correlated with PI-PLC's catalytic properties.
      Binding of the enzyme to micelles and bilayers of zwitterionic phosphocholines is
      accompanied by an increase in the fluorescence emission from tryptophan, whereas
      a decrease in the emission is observed with synthetic anionic lipids containing a
      phosphomethanol head group. A similar decrease in the tryptophan emission is
      observed with phosphatidylinositol (PI) analogues containing the phospho-D-1-myo
      inositol head group, but not with the enantiomeric L-1-myo-inositol. In
      covesicles of PI and phosphatidylcholine (PC), the rate of cleavage of PI is
      reduced because, as a neutral diluent, PC effectively reduces the surface
      concentration of PI that the bound enzyme "sees" in the interface. This permits
      determination of the interfacial Michaelis constant (KM*) as 0.26 mol fraction
      for PI as substrate. On the other hand, ditetradecylglycerophosphomethanol (DTPM)
      acts as a kinetic competitive inhibitor in the covesicles. The spectroscopic and
      catalytic activity data taken together show that PI-PLC binds to the interface of
      aqueous dispersions of phospholipids with an apparent Kd (in terms of the lipid
      monomers) of about 10-50 microM. However, only lipids with an anionic head group,
      such as phosphomethanol and phospho-D-1-myo-inositol, are able to bind as single
      molecules into the active site of the enzyme at the interface. Enantiomeric
      phospho-L-1-myo-inositol or the zwitterionic phosphocholine head group has little
      affinity for the enzyme at the interface. Thus, PI-PLC appears to obey the two
      stage, Michaelis-Menten adaptation of interfacial catalysis, according to which
      the binding of the enzyme to the interface precedes the steps of the catalytic
      turnover at the interface. Limit estimates suggest that on PI or PI/PC vesicles
      the catalysis occurs in the "scooting" mode with a moderate processivity. DTPM
      vesicles also inhibit the activity of PI-PLC toward the synthetic water-soluble
      substrate myo-inositol 1-(4-nitrophenyl phosphate), but the activity is enhanced
      severalfold in the presence of vesicles of zwitterionic phosphatidylcholine.
      Several possible explanations of this interfacial activation are considered
      within the general context of the kinetic scheme for interfacial catalysis. The
      kinetic results for the action of PI-PLC bound to vesicles are consistent with a
      model in which the interface acts as an "allosteric" effector of the catalytic
      rate constant, kcat, without affecting the substrate binding.

PMID- 8142344
TI  - Electric field and conformational effects of cytochrome c and solvent on
      cytochrome c peroxidase studied by high-resolution fluorescence spectroscopy.
AB  - Electronic spectra of mesoporphyrin-substituted yeast cytochrome c peroxidase (MP
      CcP) were measured as a function of pH, ionic strength, and binding of cytochrome
      c (cyt c) by fluorescence line narrowing (FLN) spectroscopy at 5 K. The FLN
      spectra provided information about the vibrational structure of the first excited
      singlet state of MP-CcP, the various tautomeric forms of mesoporphyrin, and the
      positions and widths of their 0,0 bands. The composite 0,0 band of MP-CcP at pH 6
      could be resolved into three components with peak positions at 16,046, 16,103,
      and 16,203 cm-1. MP-CcP at pH 8 could be analyzed using two components with peak
      positions at 16,048 and 16,193 cm-1. The disappearance of the 16,103-cm-1
      component at alkaline pH suggests that it is due to a "chemical substate" arising
      from protonation of His52 in the distal side of the porphyrin. Computer
      simulations of the electrostatic field that CcP imposes on its porphyrin show
      that, in the presence of charged axial histidines His52 and His175, the
      electrostatic field at porphyrin nitrogens increases, especially along the normal
      to the heme by about 200 mV/A. Electric field effects may account for pH
      dependent spectral shifts of the 0,0 positions of the resolved components,
      although hydrogen bonding may also affect these positions. On the other hand, the
      peak position of the components was not affected by ionic strength or binding of
      cyt c, implying that the electrostatic field of the heme pocket of MP-CcP remains
      unchanged. Indeed, computed changes in ionic strength of the solvent show no
      modification of the electrostatic field at the porphyrin. The only detectable
      effect of ionic strength and binding of cyt c to MP-CcP is on the relative
      contributions of the components, suggesting some rearrangements in the vicinity
      of the heme. Finally, shifts in the position of the vibrational lines for MP-CcP
      components indicate either that the tautomers have different vibrational
      frequencies due to the nonsymmetry of the porphyrin and/or that tautomers
      experience various distortions. Comparison of the vibrational spectrum of the
      first excited singlet state of mesoporphyrin in CcP and horseradish peroxidase
      also suggests that the heme pocket in the two peroxidases provides different
      steric restrictions.

PMID- 8142345
TI  - Crystal structure of a mispaired dodecamer, d(CGAGAATTC(O6Me)GCG)2, containing a
      carcinogenic O6-methylguanine.
AB  - The crystal structure of the synthetic deoxydodecamer d(CGAGAATTC(O6Me)GCG)2 has
      been determined and refined to an R-factor of 16.9% with data up to 2.9-A
      resolution. This sequence contains two mismatched base pairs between O6
      methylguanine and adenine with the arrangement A(syn).(O6-Me)G(anti) which
      differs from the geometry observed in solution by NMR. The intermolecular
      arrangement is equivalent to the other isomorphous deoxydodecamers. However, the
      weakening of some significant crystal packing contacts was observed and related
      to the effect of stacking between the mispaired adenine and the adjacent guanine
      in the sequence. The structure is highly hydrated, with a total of 49 solvent
      molecules located. The methyl group and the mismatched base-pair geometry locally
      disrupt the B-DNA-type solvent network with two solvent molecules found close to
      the N1 and N6 of the mispaired adenine.

PMID- 8142346
TI  - Analogs of reaction intermediates identify a unique substrate binding site in
      Candida rugosa lipase.
AB  - The structures of Candida rugosa lipase-inhibitor complexes demonstrate that the
      scissile fatty acyl chain is bound in a narrow, hydrophobic tunnel which is
      unique among lipases studied to date. Modeling of triglyceride binding suggests
      that the bound lipid must adopt a "tuning fork" conformation. The complexes,
      analogs of tetrahedral intermediates of the acylation and deacylation steps of
      the reaction pathway, localize the components of the oxyanion hole and define the
      stereochemistry of ester hydrolysis. Comparison with other lipases suggests that
      the positioning of the scissile fatty acyl chain and ester bond and the
      stereochemistry of hydrolysis are the same in all lipases which share the
      alpha/beta-hydrolase fold.

PMID- 8142347
TI  - Calcium and phospholipid binding properties of synthetic gamma-carboxyglutamic
      acid-containing peptides with sequence counterparts in human protein C.
AB  - Two peptides with counterpart sequences in the gamma-carboxyglutamic acid (Gla)
      domain of human protein C (PC) have been synthesized and characterized. One
      peptide contained 38 amino acids (38-mer) and spanned the region from the amino
      terminus of the protein to the DNA splice junction between the Gla domain and the
      following short helical stretch, and the second peptide (48-mer) included a 10
      amino acid extension that has been designed to incorporate the exon for the
      helical segment that is thought to play a role in stabilizing the Ca(2+)
      dependent conformation of the Gla domain of proteins of this class. The peptides
      were synthesized by solid-phase methodology, then oxidized to allow disulfide
      pairing, and finally purified by FPLC methodology. Chemical characterization
      showed that each peptide contained its full complement of Gla residues. Two types
      of Ca(2+)-binding sites were found in these peptides, tighter sights (2-3) with
      Kd values of 60-370 microM and a weaker set of sites (7-10) with a range of Kd
      values from 0.8 to 3.1 mM. In general, the 48-mer interacted with Ca2+ more
      tightly than the 38-mer. As revealed by circular dichroism analysis, and by
      reactivity with monoclonal antibodies that recognize both the unfolded form of
      the Gla domain as well as the Ca(2+)-dependent conformation of this same domain,
      the 38-mer and 48-mer underwent the Ca(2+)-induced conformational changes
      characteristic of the intact protein. Both peptides displayed Ca(2+)-dependent
      binding to negatively charged phospholipid vesicles (PL).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8142348
TI  - Involvement of tyrosine-76 of the kringle 2 domain of tissue-type plasminogen
      activator in its thermal stability and its omega-amino acid ligand binding site.
AB  - A series of conservative and radical mutations have been made at an aromatic
      residue, Y76, of the isolated kringle 2 domain of tissue-type plasminogen
      activator ([K2tPA]) in order to assess the importance of this residue in the
      ligand binding properties and structural stability of this protein domain. We
      have successfully expressed in Escherichia coli r-[K2tPA] variants with the
      following amino acid mutations at Y76: Y76-->A, Y76-->E, Y76-->F, Y76-->K, Y76-
      >L, Y76-->Q, and Y76-->W. The binding constants of 6-aminohexanoic acid (EACA)
      and 7-aminoheptanoic acid (7-AHpA) to each of these mutants were investigated by
      titration of the alterations in intrinsic fluorescence of the mutant kringles
      with these amino acid ligands. Compared to the wild-type kringle (r-[K2tPA]),
      which possessed dissociation constants (Kd) of 43 and 6 microM, respectively, for
      EACA and 7-AHpA, only the Y76-->E mutant displayed a substantially increased Kd
      value for these amino acids, viz., 117 microM for 7-AHpA. More moderate increases
      in this parameter were observed for the Y76-->A and Y76-->K variants (2-3-fold
      increases in the Kd), with no significant differences noted in the cases of Y76-
      >L, Y76-->Q, and Y76-->W. A most interesting observation was made with the Y76-
      >F mutant, which showed a 4-6-fold reduction in the Kd for these amino acid
      ligands. The conformations of all of the mutants were less stable than that of
      wtr-[K2tPA], as revealed by thermal denaturation studies, suggesting that a Y at
      sequence position 76 is of importance to the conformational stability of this
      kringle domain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142349
TI  - Solution structure and dynamics of ras p21.GDP determined by heteronuclear three-
      and four-dimensional NMR spectroscopy.
AB  - A high-resolution solution structure of the GDP form of a truncated version of
      the ras p21 protein (residues 1-166) has been determined using NMR spectroscopy.
      Ras p21 is the product of the human ras protooncogene and a member of a
      ubiquitous eukaryotic gene family which is highly conserved in evolution. A
      virtually complete assignment (13C, 15N, and 1H), including stereospecific
      assignments of 54 C beta methylene protons and 10 C gamma methyl protons of
      valine residues, was obtained by analysis of three- and four-dimensional (3D and
      4D) heteronuclear NMR spectra using a newly developed 3D/4D version of the ANSIG
      software. A total of 40 converged structures were computed from 3369 experimental
      restraints consisting of 3,167 nuclear Overhauser effect (NOE) derived distances,
      14 phi and 54 chi 1 torsion angle restraints, 109 hydrogen bond distance
      restraints, and an additional 25 restraints derived from literature data defining
      interactions between the GDP ligand, the magnesium ion, and the protein. The
      structure in the region of residues 58-66 (loop L4), and to a lesser degree
      residues 30-38 (loop L2), is ill-defined. Analysis of the dynamics of the
      backbone 15N nuclei in the protein showed that residues within the regions 58-66,
      107-109, and, to a lesser degree, 30-38 are dynamically mobile on the nanosecond
      time scale. The root mean square (rms) deviations between the 40 solution
      structures and the mean atomic coordinates are 0.78 A for the backbone heavy
      atoms and 1.29 A for all non-hydrogen atoms if all residues (1-166) are included
      in the analysis. If residues 30-38 and residues 58-66 are excluded from the
      analysis, the rms deviations are reduced to 0.55 and 1.00 A, respectively. The
      structure was compared to the most highly refined X-ray crystal structure of ras
      p21.GDP (1-189) [Milburn, M. V., Tong, L., de Vos, A. M., Brunger, A. T.,
      Yamaizumi, Z., Nishimura, S., & Kim, S.-H. (1990) Science 24, 939-945]. The
      structures are very similar except in the regions found to be mobile by NMR
      spectroscopy. In addition, the second alpha-helix (helix-2) has a slightly
      different orientation. The rms deviation between the average of the solution
      structures and the X-ray crystal structure is 0.94 A for the backbone heavy atoms
      if residues 31-37 and residues 59-73 are excluded from the analysis.

PMID- 8142350
TI  - Structure of glucagon-like peptide (7-36) amide in a dodecylphosphocholine
      micelle as determined by 2D NMR.
AB  - We have used 2D 1H NMR to determine the structure of glucagon-like peptide-1-(7
      36) amide bound to a dodecylphosphocholine micelle. In this membranelike
      environment, the peptide hormone is shown to have a structure similar to that
      observed for glucagon. It consists of an N-terminal random coil segment (residues
      1-7), two helical segments (7-14 and 18-29), and a linker region (15-17). The C
      terminal helix is more stable than the N-helix as determined by amide proton
      exchange experiments. The C-terminal helix shows much larger alpha and amide
      proton upfield secondary shifts relative expected for a random coil conformation.
      This suggests a highly helical structure in this portion of the molecule. The C
      terminal helix also has a much larger fraction of residues that are hydrophobic,
      presumably enhancing the interaction of this portion of the peptide with the
      micelle (or membrane). The structure refined from the NOESY data is not a uniform
      alpha-helix throughout residues 6-30. A uniform helix would not be perfectly
      amphiphilic since the hydrophobic face of the N-terminal portion of the helix is
      positioned in nearly perfect opposition to the hydrophobic face of the C-terminal
      portion. However, helical distortion around residues 15-17 allows a phase shift
      of the two helical segments to position nearly all of the hydrophobic residues
      (and none of the hydrophilic ones) on a single face of the distorted single helix
      as would be required to favorably interact with the hydrophobic portion of the
      micelle or membrane.

PMID- 8142351
TI  - 1H, 13C, 15N nuclear magnetic resonance backbone assignments and secondary
      structure of human calcineurin B.
AB  - The calmodulin- and calcium-stimulated protein phosphatase calcineurin, PP2B,
      consists of two subunits: calcineurin B, which binds Ca2+, and calcineurin A,
      which contains the catalytic site and a calmodulin binding site. Heteronuclear 3D
      and 4D NMR experiments were carried out on a recombinant human calcineurin B
      which is a 170-residue protein of molecular mass 19.3 kDa, uniformly labeled with
      15N and 13C. The nondenaturing detergent CHAPS was used to obtain a monomeric
      form of calcineurin B. Three-dimensional triple resonance experiments yielded
      complete sequential assignment of the backbone nuclei (1H, 13C, and 15N). This
      assignment was verified by a 4D HN(COCA)NH experiment carried out with 50%
      randomly deuteriated and uniformly 15N- and 13C-enriched calcineurin B. The
      secondary structure of calcineurin B has been determined on the basis of the 13C
      alpha and 13C beta secondary chemical shifts, J(HNH alpha) couplings, and NOE
      connectivities obtained from 3D 15N-separated and 4D 13C/15N-separated NOESY
      spectra. Calcineurin B has eight helices distributed in four EF-hand, helix-loop
      helix [Kretsinger, R. H. (1980) CRC Crit. Rev. Biochem. 8, 119-174] calcium
      binding domains. The secondary structure of calcineurin B is highly homologous to
      that of calmodulin. In comparison to calmodulin, helices B and C are shorter
      while helix G is considerably longer. As was observed for calmodulin in solution,
      calcineurin B does not have a single long central helix; rather, helices D and E
      are separated by a six-residue sequence in a flexible nonhelical conformation.

PMID- 8142352
TI  - Stereospecificity of substrate usage by glyoxalase 1: nuclear magnetic resonance
      studies of kinetics and hemithioacetal substrate conformation.
AB  - The specificity of glyoxalase 1 for the diastereomers of its hemithioacetal
      substrate [which forms spontaneously between an alpha-keto aldehyde and reduced
      glutathione (GSH)] was investigated by exploiting the differences between their
      1H NMR spectra at pH* 4.4. The 1H NMR spectra of the hemithioacetals of
      glutathione with phenylglyoxal or methylglyoxal were assigned with the aid of
      conventional decoupling and two-dimensional NMR spectroscopic techniques. The
      rate of interconversion of the diastereomers was determined at 30 degrees C from
      the results of an inversion-transfer technique and found to be 0.30 +/- 0.04 s-1
      (+/- sd) in the case of phenylglyoxal and 0.15 +/- 0.02 s-1 in the case of
      methylglyoxal. Stereopreference of the enzyme was tested by the addition of large
      amounts of yeast glyoxalase 1 to a reaction mixture; glyoxalase 1 preferentially
      operated on one diastereomer of the phenylglyoxal hemithioacetal but the
      diastereomers of methylglyoxal appeared to be operated upon indiscriminately.
      From computer models of the kinetics of possible reaction schemes, a mechanism
      involving glyoxalase 1 catalysis of both diastereomers of the hemithioacetals was
      shown to be the most consistent with the experimental data. Estimates of
      internuclear distances in the diastereomers, obtained from 2D NMR spectra were
      used in "dynamical simulated annealing" calculations to generate likely
      structures of the substrates. Relative ring-current shifts obtained from 1D NMR
      spectra were used, together with a ring-current shift algorithm, to select
      structures with compatible conformations. We conclude that the rate of conversion
      of substrate by the enzyme is dependent upon the overall conformation of the
      substrate molecule, rather than merely its stereochemical configuration (R or S).

PMID- 8142353
TI  - 1H and 15N nuclear magnetic resonance assignments, secondary structure in
      solution, and solvent exchange properties of azurin from Alcaligenes
      denitrificans.
AB  - Complete sequential 1H and 15N resonance assignments for the reduced Cu(I) form
      of the blue copper protein azurin (M(r) = 14,000, 129 residues) from Alcaligenes
      denitrificans have been obtained at pH 5.5 and 32 degrees C using homo- and
      heteronuclear two-dimensional and heteronuclear three-dimensional NMR
      spectroscopy. Comparison of the resonance assignments for the backbone protons
      with those of Pseudomonas aeruginosa azurin, which is 68% homologous in its amino
      acid sequence and has a very similar three-dimensional structure, showed a high
      similarity in chemical shift positions. After adjustment for random coil
      contributions the mean difference in NH chemical shifts is 0.00 ppm (root mean
      square width = 0.30 ppm), whereas for C alpha protons the mean difference is 0.09
      ppm (root mean square width = 0.23 ppm). Characteristic NOE connectivities and
      3JHN alpha values were used to determine the secondary structure of azurin in
      solution. Two beta-sheets, one helix, and nine tight and four helical turns were
      identified, and some long-range NOE contacts were found that connect the helix
      with the beta-sheets. The secondary structure obtained is in agreement with the
      structure derived from X-ray diffraction data [Baker, E. N. (1988) J. Mol. Biol.
      203, 1071-1095]. Studies of the hydration of the protein in the vicinity of the
      copper ligand residue His117 revealed that the solvent-exposed N epsilon 2 of
      His117 is in slow exchange with the bulk solvent. However, no evidence was
      obtained for the presence of a long-lived water molecule at the position
      corresponding to a well-defined water molecule observed in the crystal structures
      of A. denitrificans and Ps. aeruginosa azurin.

PMID- 8142354
TI  - Resonance Raman spectroscopic evidence for the FeS4 and Fe-O-Fe sites in
      rubrerythrin from Desulfovibrio vulgaris.
AB  - Resonance Raman (RR) spectra of the non-heme iron protein rubrerythrin from
      Desulfovibrio vulgaris unequivocally demonstrate the presence of both a
      rubredoxin-type FeS4 site and a (mu-oxo)diiron(III) cluster. The RR spectra of
      rubrerythrin excited at 496.5 and 568.2 nm are dominated by bands similar to
      those of rubredoxin and conform to the vibrational pattern expected for a
      distorted FeS4 tetrahedron of an Fe(S-Cys)4 site. Numerous overtone and
      combination bands of the Fe-S stretches are also observed, and a band at 650 cm-1
      is assigned to a cysteine C-S stretching mode. The 374-, 355-, and 340-cm-1
      bands, assigned to the three components of the v3(T2) asymmetric FeS4 stretching
      mode, are 2-8 cm-1 lower than the corresponding frequencies for the Desulfovibrio
      gigas rubredoxin FeS4 site. Similar differences in frequencies of bands assigned
      to SFeS bending modes between rubredoxin and rubrerythrin are also detected.
      These frequency differences imply either slightly weaker Fe-S bonds or subtle
      conformational differences among the cysteinyl ligands in the rubrerythrin versus
      rubredoxin FeS4 sites. The RR spectrum of rubrerythrin excited at 406.7 nm shows
      dramatically diminished intensities of the FeS4 bands with concomitant
      enhancement of a band at 514 cm-1. This band shifts 18 cm-1 to lower frequency
      when the protein is dissolved in H(2)18O. The frequency of this band and the 18O
      isotope shift are those expected for the symmetric Fe-O-Fe stretch of a bent oxo
      bridged diiron(III) cluster and indicate that this cluster has at least one
      additional bridging ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142355
TI  - Spectroscopic observation of the intramolecular electron transfer in the
      photoactivation processes of nitrile hydratase.
AB  - The photoactivation phenomena of the photosensitive enzyme nitrile hydratase
      (NHase) was studied by various spectroscopic methods. We have already shown that
      the photoactivation of NHase accompanies oxidation of an iron atom in the NHase
      [Honda et al. (1992) FEBS Lett. 301, 177-180]. From the results obtained in the
      present study by absorption, action, and fluorescence spectra, we show that the
      chromophore responsible for the photoactivation process is the iron complex, and
      the tryptophan residues in NHase induce the oxidation of the iron atom via an
      energy-transfer process. The nanosecond flash photolysis experiment revealed that
      this photoactivation process is completed within 50 ns, which suggests that the
      changes observable in the absorption spectra originate from an intramolecular
      electron transfer occurring from an electronically excited state. Also the role
      of a stabilizing reagent, namely, n-butyric acid (BA), was investigated using the
      above methods, which revealed that BA, besides its stabilizing effect,
      contributes to the increase in apparent photoactivation rate.

PMID- 8142356
TI  - Isothermal titration calorimetric study of the association of hen egg lysozyme
      and the anti-lysozyme antibody HyHEL-5.
AB  - The thermodynamics of association of hen egg lysozyme and the antibody HyHEL-5
      was characterized by isothermal titration calorimetry. The structure of this
      complex has been determined to 2.8-A resolution by Sheriff et al. [Sheriff, S.,
      Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C.,
      & Davies, D. R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8075-8079]. The
      calorimetric enthalpy of association is negative and declines linearly with
      temperature in the range 10-37 degrees C (delta Cp = -340 +/- 40 cal mol-1 K-1).
      Entropic contributions calculated using previously determined values of the
      affinity of association are negative (unfavorable) in this temperature range.
      This result is consistent with the loss of mobility upon association of the
      unusually mobile segments of HEL which form the HyHEL-5 epitope. As the affinity
      of association is approximately constant in this temperature range, an enthalpy
      entropy compensation effect is implied. The hydrophobic and vibrational
      contributions to delta S and delta Cp are estimated using the method of
      Sturtevant [Sturtevant, J. M. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 2236
      2240]. The experimental value of delta Cp is in rather close agreement with the
      delta Cp estimated from the polar and nonpolar surface areas buried upon
      association.

PMID- 8142357
TI  - Conformational analysis of two cyclic analogs of angiotensin: implications for
      the biologically active conformation.
AB  - Conformations of two cyclic analogs of angiotensin (Asp1-Arg2-Val3-Tyr4-Val/Ile5
      His6-Pro7-Phe8, AT), cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT,
      were studied, independently employing two complementary techniques, energy
      calculations and NMR measurements in DMSO solution. NMR data were indicative of
      well-defined solution conformations for the cyclic moieties of cyclo[Sar1, Cys3,
      Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT, including the phi values for the
      Cys3/HCys3 and Tyr4 residues, as well as the chi 1 value for the Tyr4 residue.
      Solution conformations for the exocyclic linear parts of both molecules cannot be
      described by the NMR data with the same precision. At the same time, independent
      energy calculations revealed the same conformations of cyclic moieties of
      cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT among low-energy
      conformers for both peptides. Moreover, the same conformations are compatible
      with the model of AT receptor-bound conformation (Nikiforovich & Marshall, 1993),
      which assumes the particular spatial arrangement of aromatic moieties of Tyr4,
      His6, and Phe8 residues and the C-terminal carboxyl. These conformers of
      cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT contain "an open turn"
      in the backbone of the Tyr4-Val5 residues, instead of the earlier proposed beta
      like reversal, thus confirming the suggestion that the conformation(s) ensuring
      binding of AT analogs with specific receptors should not be described in terms of
      a unique backbone conformer.

PMID- 8142358
TI  - Conformational studies of human plasminogen and plasminogen fragments: evidence
      for a novel third conformation of plasminogen.
AB  - The conformations of Glu-plasminogen and defined proteolytic fragments, in the
      presence and absence of 6-aminohexanoic acid (6-AHA), trans-4
      (aminomethyl)cyclohexanecarboxylic acid (t-AMCHA), and benzamidine, were studied
      using three methods: size-exclusion high-performance liquid chromatography (SE
      HPLC), small-angle X-ray scattering (SAXS), and dynamic laser light scattering
      (DLLS). The well-documented conformational change of Glu-plasminogen with 6-AHA
      or t-AMCHA was measured as a decrease in molecular elution time by SE-HPLC (8.93
      +/- 0.01 to 8.32 +/- 0.01 min) and increases in radius of gyration (30.7 +/- 0.1
      to 49.8 +/- 0.3 A) and Stokes radius (40.6 +/- 0.3 to 48.5 +/- 0.3 A) by SAXS and
      DLLS, respectively. The addition of benzamidine to Glu-plasminogen resulted in a
      conformation (radius of gyration 41.0 +/- 0.4 A and Stokes radius 46.6 +/- 0.3 A)
      distinct from that in the presence of 6-AHA. 6-AHA, but not benzamidine, induced
      significant conformational changes in Lys-plasminogen and kringles 1 + 2 + 3 + 4
      + 5. We conclude that Glu-plasminogen adopts three distinct conformations
      involving two intramolecular interactions: one mediated by regions of the NH2
      terminal peptide and kringle 5, competed for by 6-AHA or benzamidine, and the
      other possibly between kringles 3 and 4, competed for by 6-AHA but not
      benzamidine.

PMID- 8142359
TI  - Identification and characterization of aspartate residues that play key roles in
      the allosteric regulation of a transcription factor: aspartate 274 is essential
      for inducer binding in lac repressor.
AB  - To explore the roles of three aspartate residues, Asp88, Asp130, and Asp274,
      found in the proposed inducer binding site of lac repressor [Sams, C. F., Vyas,
      N. K., Quiocho, F. A., & Matthews, K. S. (1984) Nature 310, 429-430], each site
      was substituted with alanine, glutamate, lysine, or asparagine by site-specific
      mutagenesis. The mutations at the Asp88 site resulted in a 5-13-fold decrease in
      inducer binding affinity, largely due to an increase in the inducer dissociation
      rate constants for these mutants. In addition, the mutant proteins Asp88-->Ala
      and Asp88-->Lys exhibited altered allosteric behavior for inducer binding. These
      data conflict with the original hypothesis placing Asp88 in the inducer binding
      site, but are in agreement with a recent model that places this amino acid close
      to the subunit interface involved in cooperativity associated with inducer
      binding [Nichols, J. C., Vyas, N. K., Quiocho, F. A., & Matthews, K. S. (1993) J.
      Biol. Chem. 268, 17602-17612; Chen, J., & Matthews, K. S. (1992) J. Biol. Chem.
      267, 13843-13850]. Substitution at Asp130 did not alter the inducer binding
      affinity nor other binding activities. Thus, this amino acid is not crucial in
      the binding to beta-substituted monosaccharides or in protein function. In stark
      contrast, all mutant proteins with substitutions at the Asp274 site exhibited no
      detectable inducer binding. With the exception of Asp274-->Lys, the structures of
      these mutant proteins appear to be similar to wild-type. The data demonstrate
      that Asp274 plays a crucial role in inducer binding of this transcriptional
      regulator.

PMID- 8142360
TI  - Factors affecting the stability and conformation of Locusta migratoria
      apolipophorin III.
AB  - Apolipophorin III (apoLp-III) from the migratory locust, Locusta migratoria,
      represents the only full-length apolipoprotein whose three-dimensional structure
      has been solved. In the present study, spectroscopic methods have been employed
      to investigate the effects of deglycosylation (via endoglycosidase F treatment)
      and complexation with lipid on the stability and conformation of this protein.
      Addition of isolated lipid-free apoLp-III to sonicated vesicles of
      dimyristoylphosphatidylcholine (DMPC) resulted in the formation of relatively
      uniform disklike complexes with an average Strokes diameter of 13.5 nm. Flotation
      equilibrium experiments conducted in the analytical ultracentrifuge revealed a
      particle molecular mass of 588 500 Da. Chemical cross-linking and compositional
      analysis of apoLp-III.DMPC complexes indicated five apoLp-III molecules per disk
      and an overall DMPC:apoLp-III molar ratio of 122:1. Circular dichroism (CD)
      spectra of apoLp-III samples suggested a loss of alpha-helical structure upon
      deglycosylation, while complexation with DMPC did not significantly alter the
      helix content (estimated to be > 75%). Fluorescence spectroscopy revealed that
      the apoLp-III tryptophan fluorescence emission maximum was blue-shifted from 347
      to 332 and 321 nm upon deglycosylation and complexation with DMPC, respectively.
      In quenching experiments with native apoLp-III, tryptophan residues were shielded
      from the positively charged quencher, CsCl. Increased exposure to KI, CsCl, and
      acrylamide was observed upon deglycosylation, whereas complexation with DMPC
      yielded lower Ksv values for KI and acrylamide and an increased value for CsCl
      versus native lipid-free apoLp-III. In guanidine hydrochloride denaturation
      studies monitored by CD or fluorescence, native, lipid-free apoLp-III displayed a
      denaturation midpoint of 0.60 M, and delta GDH2O = 5.37 kcal/mol was
      calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142361
TI  - Biotin synthase: purification, characterization as a [2Fe-2S]cluster protein, and
      in vitro activity of the Escherichia coli bioB gene product.
AB  - We report here the first purification of the protein encoded by the Escherichia
      coli bioB gene. One species of this protein runs on native gels with an
      electrophoretic mobility typical of a protein with m = 82 kDa, suggesting the
      protein is a dimer (gene sequence predicts m = 38.7 kDa). There are two iron- and
      two acid-labile sulfur atoms per protein monomer. Solutions containing the
      protein are red and have an absorbance spectrum characteristic of proteins with
      [2Fe-2S] clusters. In its oxidized native state, the protein is EPR-silent. Upon
      addition of dithionite, the protein's UV-visible absorbance spectrum is very
      slowly bleached, and an EPR active species is produced that displays a signal at
      gavg = 1.95. All these results are consistent with this protein containing one
      [2Fe-2S] cluster per monomer. The EPR spin quantitation is only 5-10% of
      expected. Since this protein loses iron upon reduction with dithionite, the low
      spin quantitation is probably due to cluster instability in the reduced state.
      Another species of the bioB gene products has also been purified which runs on
      native gels with an electrophoretic mobility typical of a protein with m = 104
      kDa. This species appears to be a dimer with one [2Fe-2S] cluster per dimer. The
      104-kDa protein can be converted to the 82-kDa protein upon incubation with Fe3+
      and S2-. The bioB gene product we have isolated is active in the conversion of
      dethiobiotin to biotin in vitro in the presence of NADPH, AdoMet, Fe3+ or Fe2+,
      and additional unidentified factors from the crude extracts of E. coli. The Km
      for dethiobiotin in this reaction has been found to be 2 microM.

PMID- 8142362
TI  - Engineering plasminogen activator inhibitor 1 mutants with increased functional
      stability.
AB  - Plasminogen activator inhibitor 1 (PAI-1), a member of the serine protease
      inhibitor (Serpin) superfamily, is the primary inhibitor of the plasminogen
      activators tPA and uPA. PAI-1 is produced in an active form but converts to an
      inactive or latent form with a half-life of approximately 1 h at pH 7.5, 37
      degrees C. This study describes the construction, expression, and
      characterization of PAI-1 mutants with increased functional stability. Three
      mutations that disrupt an ion pair, present in latent PAI-1, between Arg-30 and
      Glu-350 (P4'), were introduced into recombinant PAI-1. All three mutant proteins
      maintained normal functional activity against both uPA and tPA. However, the half
      life of each purified PAI-1 mutant was extended compared to the 1.1 h observed
      for wild-type PAI-1 (wtPAI-1) (1.2 h for Glu-350-->Arg, 2.0 h for Glu-350-->Pro,
      and 2.1 h for the Arg-30-->Glu mutation). An additional PAI-1 variant containing
      a second mutation designed to potentially reconstitute the ion pair (Arg-30-
      >Glu, Glu-350-->Arg) failed to restore the wild-type half-life. Circular
      dichroism spectra analysis indicated that the active and latent forms of wtPAI-1
      and all four mutants contained similar secondary structural elements. Thermal
      stability determinations showed that latent wtPAI-1 was much more structurally
      stable than the active conformation. However, the latent form for all four
      mutants was significantly less stable than the corresponding wtPAI-1 conformer.
      This is the first report of PAI-1 mutants which have been specifically engineered
      to produce enhanced functional stability.

PMID- 8142363
TI  - Water ring structure at DNA interfaces: hydration and dynamics of DNA
      anthracycline complexes.
AB  - In crystallographic structures of biological macromolecules, one can observe many
      hydration rings that originate at one water molecule, pass via hydrogen bonds
      through several others, and return to the original water molecule. Five-membered
      water rings have been thought to occur with greater frequency than other ring
      sizes. We describe a quantitative assessment of relationships between water ring
      size and frequency of occurrence in the vicinity of nucleic acid interfaces. This
      report focuses on low-temperature X-ray crystallographic structures of two
      anthracyclines, adriamycin (ADRI) and daunomycin (DAUN), bound to d(CGATCG) and
      on several DNA structures published previously by others. We have obtained
      excellent low-temperature (-160 degrees C, LT) X-ray intensity data for d(CGATCG)
      adriamycin and d(CGATCG)-daunomycin with a multiwire area detector. The LTX-ray
      data sets contain 20% (daunomycin, LT-DAUN) and 35% (adriamycin, LT-ADRI) more
      reflections than were used to derive the original room-temperature (15 degrees C)
      structures [Frederick, C.A., Williams, L.D., Ughetto, G., van der Marel, G. A.,
      van Boom, J.H., Rich, A., & Wang, A.H.-J. (1990) Biochemistry 29, 2538-2549]. The
      results show that five-membered water rings are not preferred over other ring
      sizes. This assessment is consistent with our observation of broad dispersion W-W
      W angles (sigma = 20 degrees). In addition, we report that the thermal mobility,
      distinct from the static disorder, of the amino sugar of daunomycin and
      adriamycin is significantly greater than that of the rest of the complex. This
      mobility implies that if the central AT base pair is switched to a CG base pair,
      there should be a low energy cost in avoiding the guanine amino group. The energy
      difference (for the sugar-binding preference) between d(CGTACG) and d(CGCGCG)
      could be considerably less than 20 kcal/mol, a value proposed previously from
      computation.

PMID- 8142364
TI  - Effects of unpaired bases on the conformation and stability of three-arm DNA
      junctions.
AB  - Three-arm DNA junctions, in which three double helices intersect at a branch,
      have unique structure and reactivity of bases at and near the branch. Their
      solution conformation is asymmetric in the presence of Mg2+, while bases at the
      branch are sensitive to single-strand-specific agents. Following the surprising
      report that unpaired bases at the branch stabilize three-arm junctions, we have
      investigated the geometry and thermodynamics of three-arm junctions containing
      pendant T and A bases. The results are consistent with additional structure
      formation in junctions containing up to four pendant bases at the branch:
      relative to the tight junction, the thermal stability of junctions with two T's
      or A's at the branch increases; bases near the branch become less reactive to
      single-strand-reactive probes; and the enthalpy of formation is more negative.
      The interaction of ethidium observed at the branch in three-arm junctions is
      enhanced in junctions with unpaired bases at the branch. The geometry of three
      arm junctions is perturbed by the presence of pendant bases, as seen by measuring
      the electrophoretic mobility of junctions to which long duplex arms are appended
      pairwise.

PMID- 8142365
TI  - Molecular dynamics study of bacteriorhodopsin and artificial pigments.
AB  - The structure of bacteriorhodopsin based on electron microscopy (EM) studies, as
      provided in Henderson et al. (1990), is refined using molecular dynamics
      simulations. The work is based on a previously refined and simulated structure
      which had added the interhelical loops to the EM model of bR. The present study
      applies an all-atom description to this structure and constraints to the original
      Henderson model, albeit with helix D shifted. Sixteen waters are then added to
      the protein, six in the retinal Schiff base region, four in the retinal-Asp-96
      interstitial space, and six near the extracellular side. The root mean square
      deviation between the resulting structure and the Henderson et al. (1990) model
      measures only 1.8 A. Further simulations of retinal analogues for substitutions
      at the 2- and 4-positions of retinal and an analogue without a beta-ionone ring
      agree well with observed spectra. The resulting structure is characterized in
      view of bacteriorhodopsin's function; key features are (1) a retinal Schiff base
      counterion complex which is formed by a hydrogen bridge network involving six
      water molecules, Asp-85, Asp-212, Tyr-185, Tyr-57, Arg-82, and Thr-89, and which
      exhibits Schiff base nitrogen-Asp-85 and -Asp-212 distances of 6 and 4.6 A; (2)
      retinal assumes a corkscrew twist as one views retinal along its backbone; and
      (3) a deviation from the usual alpha-helical structure of the cytoplasmic side of
      helix G.

PMID- 8142366
TI  - Identification of the EPR-active iron-nitrosyl complexes in mammalian ferritins.
AB  - This study was undertaken to characterize the nitric oxide complexes of mammalian
      ferritin and their EPR properties to gain a better understanding of the
      interaction of NO with non-heme iron proteins within the cell. Measurements were
      made with horse spleen apo- and holoferritins, with chemically modified proteins,
      and with recombinant human H-chain apoferritin and its site-directed mutants.
      Three types of EPR signals (A, B, and C) have been identified and attributed to
      iron-nitrosyl complexes at imidazole groups of histidine, thiol groups of
      cysteine, and carboxylate groups of aspartate and glutamate, respectively. The C
      type axial spectrum has features at g perpendicular' = 4 and g parallel' = 2
      characteristic of a paramagnetic Fe(3+)-NO- complex with total spin S = 3/2 and
      probably arises from nonspecific binding to carboxylate groups on the protein.
      The S = 1/2 axial B-type signal g perpendicular' = 2.033 and g parallel' = 2.014)
      is formed at Cys-130 (human H-chain sequence numbering). His-128 and possibly His
      118 are sites of formation of the rhombic S = 1/2 A-type complex (gx' = 2.055,
      gy' = 2.033, and gz' = 2.015); the former residue perhaps plays a role in the
      conformational stability of the protein as well as in iron binding. The data
      reveal that the residues Cys-130 and His-128 in the vicinity of 3-fold channels
      leading to the interior of the protein shell are important in iron-nitrosyl
      complex formation in mammalian ferritins.

PMID- 8142367
TI  - Thermodynamic effects of reduction of the active-site disulfide of Escherichia
      coli thioredoxin explored by differential scanning calorimetry.
AB  - Intramolecular disulfide bonds in protein molecules, whether present in the wild
      type protein or engineered via site-directed mutagenesis, are capable of
      significantly increasing the stability. Establishing thermodynamic parameters
      associated with the redox formation of this linkage is often encumbered by other
      global structural changes within the protein molecule. The active site of
      Escherichia coli thioredoxin possesses a disulfide/dithiol in a short loop,
      oxidation/reduction of which is accompanied by little structural alteration of
      the protein. Data for the thermal denaturation of the reduced protein are
      presented, which on comparison to the data obtained for the oxidized form
      [Ladbury, J.E., Wynn, R., Hellinga, H.W., & Sturtevant, J.M. (1993) Biochemistry
      32, 7526-7530] are used to establish thermodynamic parameters for the redox
      reaction in this molecule. Data for an isosteric double mutation in the active
      site of thioredoxin (Cys32Ser/Cys35Ser) are also presented. Although the wild
      type and mutated proteins show a similar reduction in free energy compared to the
      oxidized form (-3.0 +/- 0.4 and -3.1 +/- 0.3 kcal mol-1, respectively), the
      enthalpic and entropic contributions to this destabilization are different for
      the two proteins.

PMID- 8142368
TI  - Influence of poly(ethylene glycol) and aqueous viscosity on the rotational
      diffusion of membranous Na,K-ATPase.
AB  - The Na,K-ATPase [ATP phosphohydrolase (Na+/K(+)-transporting), E.C. 3.6.1.37] in
      native membranes from the salt gland of Squalus acanthias has been spin-labeled
      covalently with a chloromercuri nitroxide derivative, and the rotational
      diffusion of the protein has been studied, as a function of the concentration of
      glycerol or poly(ethylene glycol) in the suspending medium, by means of
      saturation-transfer electron spin resonance spectroscopy. The effective
      rotational correlation time of the protein increases linearly with the viscosity
      of the aqueous glycerol medium, with a gradient whose value indicates that ca. 50
      70% of the volume of the Na,K-ATPase protein is external to the membrane. The
      effective rotational correlation times of the protein in poly(ethylene glycol)
      solutions are considerably greater than those in glycerol solutions of the same
      viscosity and increase nonlinearly with the viscosity of the suspending medium,
      indicating that increasing concentrations of poly(ethylene glycol) induce
      aggregation of the integral proteins within the membrane. The value reached at
      50% poly(ethylene glycol) corresponds to a degree of aggregation of the proteins
      between 2 and 5 depending on whether the ethylene glycol polymer is excluded from
      the membrane surface region. The results are discussed with respect to hydration
      forces and poly(ethylene glycol)-induced cell fusion.

PMID- 8142369
TI  - Regulation of gonadotropin mRNA levels in cultured rat pituitary cells by
      gonadotropin-releasing hormone (GnRH): role for Ca2+ and protein kinase C.
AB  - Incubation of cultured rat pituitary cells with gonadotropin-releasing hormone
      (GnRH, 1 nM) resulted in a rapid elevation of gonadotropin subunit steady-state
      mRNA levels(alpha, 2.2-fold, LH beta, 2.1-fold, and FSH beta 2.2-fold increases
      at 30 min). Addition of actinomycin D abolished the stimulatory effect of GnRH
      upon alpha and LH beta and reduced the effect upon FSH beta mRNA levels. The
      effect of GnRH is biphasic, where the early phase is being observed at 30-60 min,
      while the late phase is noticed between 12-24 h. A significant decrease in FSH
      beta mRNA levels was found after 6 h of incubation when using a stable GnRH
      analog. The unique profile of the time response enabled us to attempt to dissect
      the signal transduction cascade involved in the neurohormone action. Addition of
      the protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate (TPA),
      or the Ca2+ ionophore, ionomycin, mimicked the profile of GnRH-induced alpha and
      LH beta mRNA elevation. The two phases of FSH beta mRNA elevation induced by GnRH
      could be mimicked by TPA, while the decrease at 6 h was mimicked by ionomycin.
      The rapid stimulatory effect of GnRH on gonadotropin subunit mRNA levels was
      abolished by the PKC inhibitors, staurosporine and GF 109203X. Similarly, the
      rapid stimulatory effect of GnRH on alpha and LH beta, but not FSH beta, was
      abolished in Ca(2+)-free medium. While additivity in LH release is obtained upon
      the combined addition of TPA and ionomycin for 30 min of incubation, LH beta and
      FSH beta gene expression is inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142370
TI  - Transmembrane topography of the mitochondrial oxoglutarate carrier assessed by
      peptide-specific antibodies and enzymatic cleavage.
AB  - The folding of the peptide chain of the bovine heart oxoglutarate carrier in the
      inner mitochondrial membrane and in the membrane of reconstituted proteoliposomes
      has been investigated by enzymatic and immunochemical approaches using proteinase
      K and polyclonal site-directed antibodies, respectively. Two peptides
      corresponding to the amino acid sequences 2-12 (N-terminal peptide) and 303-314
      (C-terminal peptide) have been synthesized and coupled to ovalbumin before being
      used to immunize rabbits. The specificity of the generated antibodies was tested
      by enzyme-linked immunosorbent assay (ELISA) and by Western blot analysis. Both
      anti-N-terminal and anti-C-terminal antibodies reacted specifically with the
      corresponding peptides and with the isolated oxoglutarate carrier, whereas only
      anti-C-terminal antibodies immunodetected the carrier in mitochondrial lysates
      and reacted with the membrane-bound carrier in mitoplasts and in freeze-thawed
      mitochondria. This result indicated that the last 12 C-terminal amino acid
      residues of the oxoglutarate carrier protein are accessible from the cytosolic
      side of the inner mitochondrial membrane. Anti-C-terminal antibodies did not
      recognize the oxoglutarate carrier in reconstituted proteoliposomes unless the
      membrane was inverted, indicating that the carrier was inserted unidirectionally
      in proteoliposomes, with an orientation opposite that found in mitochondria. The
      immunological data were complemented by data from a limited proteolysis study
      performed on the membrane-bound oxoglutarate carrier in proteoliposomes, using
      proteinase K. Cleavage of the carrier caused a time-dependent inhibition of the
      oxoglutarate-oxoglutarate exchange activity of the reconstituted system. Four
      cleavage sites were identified, between Val-39 and Gln-40, between Tyr-61 and Lys
      62, between Phe-169 and Arg-170, and between Arg-182 and Gly-183.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8142371
TI  - Calcium-binding properties of a calcium-dependent protein kinase from Plasmodium
      falciparum and the significance of individual calcium-binding sites for kinase
      activation.
AB  - Calcium-dependent protein kinase from Plasmodium falciparum (PfCPK) is a
      multidomain protein composed of an N-terminal kinase domain connected via a
      linker region to a C-terminal CaM-like calcium-binding domain. The kinase can be
      activated by Ca2+ alone and associates with 45Ca2+. Here we describe the calcium
      binding properties of the kinase and the significance of the individual calcium
      binding sites with respect to enzymatic activation, as well as the Ca(2+)-induced
      conformational change as detected by circular dichroism. As predicted from the
      cDNA sequence, the kinase has four EF-hand calcium-binding sites in the C
      terminal domain. To understand the roles of the individual calcium-binding sites,
      two series of mutations were generated at the individual EF-hand motifs. The
      highly conserved glutamic acid residue at position 12 in each calcium-binding
      loop was mutated to either lysine or glutamine, and therefore a total of eight
      mutants were generated. Either of these mutations (to lysine or glutamine) is
      sufficient to eliminate calcium binding at the mutated site. Sites I and II
      appear to be crucial for both Ca(2+)-induced conformational change and enzymatic
      activation. Whereas mutations at site II almost completely abolish kinase
      activity, mutations at site I are also deleterious and dramatically reduce the
      sensitivity of the Ca(2+)-induced conformational change and the Ca(2+)-dependent
      activation. Mutations at sites III and IV have minor effects.

PMID- 8142372
TI  - Ca2+ binding to occluded sites in the CrATP-ATPase complex of sarcoplasmic
      reticulum: evidence for two independent high-affinity sites.
AB  - Occluded Ca2+ sites in the CrATP-ATPase complex are studied by first forming the
      complex in the presence of EGTA so that the sites can be occluded while vacant.
      45Ca2+ binding to the occluded sites is then studied under equilibrium
      conditions. Binding curves are produced for two independent Ca2+ sites with Kd(1)
      = 0.2 microM and Kd(2) = 1.6 microM. When both sites are saturated, only the Ca2+
      bound to the lower affinity site can exchange with free Ca2+. On addition of EGTA
      (15 vs 0.5 mM Ca2+) all bound Ca2+ dissociates, the net dissociation rate of one
      half of the Ca2+ being approximately 10-fold greater than that of the other one
      half (at 37 degrees C). When Ca2+ is bound only to the higher affinity site, this
      Ca2+ will exchange slowly if the concentration of free Ca2+ is below the
      saturation level of the lower affinity site. An ionophore dependency of the rates
      of binding and dissociation indicates that the access to the sites is through the
      interior of the vesicle. Solubilization in C12E9 releases the Ca2+ in the higher
      affinity site. Our observations are consistent with a model of the ATPase where
      the lower affinity of two transport sites is associated with the interior
      position (closest to the lumen) in a transmembrane channel. It is further evident
      that when in the occluded state, the higher affinity site is available without
      Ca2+ first being bound to the lower affinity site, eliminating cooperativity from
      the binding mechanism. In turn, this implies a connection between the integrity
      of the high-affinity binding site and the linking of sections of the catalytic
      site by CrATP.

PMID- 8142373
TI  - Nitrous oxide degradation by cobalamin-dependent methionine synthase:
      characterization of the reactants and products in the inactivation reaction.
AB  - Cobalamin-dependent methionine synthase catalyzes the remethylation of
      homocysteine to form methionine, using methyltetrahydrofolate as the primary
      methyl donor. The enzyme is susceptible to inactivation by the anaesthetic gas,
      nitrous oxide, through either short-term exposure to high levels or chronic
      exposure to low levels of this agent. We have studied the chemical reaction
      wherein the bound cobalamin prosthetic group of the enzyme from Escherichia coli
      catalyzes the degradation of nitrous oxide. By poising the enzyme at low ambient
      potentials in an electrochemical cell, the concentration of enzyme in the highly
      reactive cob(I)alamin state can be controlled, and the observed rate of
      inactivation is directly dependent upon the amount of enzyme in this redox state.
      The inactivation consumes both nitrous oxide and electrons, while nitrogen gas is
      evolved. The inactivation process is also directly dependent upon the proton
      concentration, but the effect of pH was found to be on the enzyme, revealing a
      redox-linked base presumed to be on or near the cobalamin. The chemical reaction
      between enzyme-bound cob(I)alamin and nitrous oxide that leads to inactivation is
      therefore independent of pH. In a single turnover experiment, where enzyme-bound
      cob(I)alamin is generated from methylcobalamin by methyl transfer to the
      substrate homocysteine, the cob(I)alamin decays to cob(II)alamin, suggesting that
      the degradation of nitrous oxide involves one-electron reduction of nitrous
      oxide. We propose that the inactivation chemistry is likely to be a one-electron
      reduction of nitrous oxide, which leads to the formation of a highly reactive
      oxidant, such as hydroxyl radical, and subsequent enzyme damage.

PMID- 8142374
TI  - Nitrous oxide inactivation of cobalamin-dependent methionine synthase from
      Escherichia coli: characterization of the damage to the enzyme and prosthetic
      group.
AB  - Nitrous oxide, or laughing gas, is an anaesthetic agent that inactivates
      cobalamin-dependent methionine synthase. This enzyme uses the highly reactive,
      enzyme-bound cob(I)alamin oxidation state of the prosthetic group to effect
      methyl group transfer from 5-methyltetrahydrofolate to homocysteine to form
      tetrahydrofolate and methionine. The cob(I)alamin is capable of reductively
      degrading nitrous oxide, and here we characterize the modifications that occur to
      the Escherichia coli enzyme following electrochemical inactivation. Methionine
      synthase was inactivated on a milligram scale by equilibrating enzyme containing
      bound cob(II)alamin with a reduced electrochemical mediator to give the reactive
      cob(I)alamin state under an anaerobic atmosphere of nitrous oxide. The primary
      damage occurs to a 37.2-kDa domain that binds S-adenosylmethionine (AdoMet), and
      inactive enzyme can no longer be reductively methylated using AdoMet. The damage
      is oxidative, and it includes the covalent addition of the mediator, triquat, to
      the enzyme selectively at valine 1177, as well as the formation of a covalent
      cross-link between peptides containing the only two cysteines within this domain.
      Spectrally, the prosthetic group bound to inactive enzyme resembles
      cob(II)alamin, although some loss in absorbance is apparent. When the enzyme was
      reconstituted with [57Co]cobalamin and the inactivation repeated, the cobalamin
      was recovered unmodified in approximately 75% yield, but two products derived
      from the cobalamin were also observed. We interpret the finding of oxidatively
      modified products as strong evidence that reductive degradation of nitrous oxide
      releases a potent oxidant, presumably hydroxyl radical or its equivalent, that is
      capable of modifying sites proximal to the cobalamin.

PMID- 8142375
TI  - Isolation and structure of a third form of liver microsomal flavin monooxygenase.
AB  - Flavin-containing monooxygenases (FMOs) catalyze NADPH-dependent oxygenation of
      nucleophilic nitrogen, sulfur, and phosphorous atoms in various drugs,
      pesticides, and xenobiotics. Two forms of this enzyme have been isolated and
      characterized from rabbit liver microsomes [Ozols, J. (1989) Biochem. Biophys.
      Res. Commun. 163, 49-55]. The isolation and the structure of a third isoform
      (FMO3) is presented here. The isolation procedure for FMO3 included
      solubilization of liver microsomes with cholate, poly(ethylene glycol)
      precipitation, chromatography on anion- and cation-exchange and hydroxyapatite
      columns in the presence of nonionic detergents and glycerol. On sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, FMO3 exhibited a distinct, single
      band with a M(r) higher than those of FMO1 and FMO2. FMO3 copurified with a
      polypeptide complex of high FMO activity. This complex consisted of three
      polypeptides, named FMO3, FMO1a, and FMO2a. The column chromatographic behavior
      of FMO1 a and 2a was distinct from that of FMO1 and 2. The electrophoretic
      mobility of FMO1a was identical to that of FMO1. Automated sequence analysis of
      this polypeptide complex indicated the presence of only one predominant peptide
      with an open N-terminus. The derived N-terminal amino acid sequence of some 20
      residues was identical to the N-terminus of FMO2. The FMO complex, however, did
      not contain a polypeptide corresponding to the electrophoretic mobility of FMO2.
      The N-terminus of FMO3 was blocked by an acetyl residue. Automated Edman
      degradation of peptides obtained from chemical and enzymatic digests established
      the amino acid sequence of some 514 residues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142376
TI  - Mechanism of inactivation of S-adenosylhomocysteine hydrolase by (E)-5',6'
      didehydro-6'-deoxy-6'-halohomoadenosines.
AB  - S-Adenosylhomocysteine (AdoHcy) hydrolase is irreversibly inactivated by (E)
      5',6'-didehydro-6'-deoxy-6'-halohomoadenosines (EDDHHAs, halogen = I, Br, and
      Cl). The inactivation is concomitant with the reduction of the enzyme-bound NAD+
      (E.NAD+) to NADH, the release of halide ion, and the formation of adenine (Ade)
      from the EDDHHAs. The mechanism of this inactivation involves two catalytic
      pathways. Pathway a involves a rapid addition of water to the 5',6'-bond of
      EDDHHAs and elimination of halide ion, resulting in the formation of 6'
      carboxaldehyde 1 which then degrades chemically, resulting in the formation of
      Ade. Alternatively, 6'-carboxyaldehyde 1 can be oxidized by E.NAD+ to form 3'
      keto-6'-carboxaldehyde 3 and the NADH form (inactive) of the enzyme. Like 6'
      carboxaldehyde 1, the 3'-keto derivative 3 degrades chemically to form Ade.
      Pathway b involves the oxidation of EDDHHAs to 3'-keto-EDDHHAs 2 by E.NAD+, as
      the first step, and the subsequent release of halide ion to form 3'-keto-6'
      carboxaldehyde 3. Evidence in support of these mechanisms includes the
      observations that incubation of EDDHHAs with AdoHcy hydrolase generated large
      molar excesses of halide ions and Ade, that Ade was shown to eliminate
      spontaneously from 6'-carboxaldehyde 1, and that the more rapid the halide ion
      release (Cl- > Br- > I-) from the EDDHHAs or the greater the partition ratios
      (nonlethal turnovers/lethal event), the lower the enzyme inactivation
      efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142377
TI  - Identification of active-site peptides from 3H-labeled 2-ethynylnaphthalene
      inactivated P450 2B1 and 2B4 using amino acid sequencing and mass spectrometry.
AB  - 2-Ethynylnaphthalene (2EN) is a mechanism-based inactivator of rat cytochrome
      P450 (P450) 2B1 with 1.3 mol of adduct bound per mole of P450 inactivated
      [Roberts, E.S., Hopkins, N.E., Alworth, W.L., & Hollenberg, P.F. (1993) Chem.
      Res. Toxicol. 6, 470-479]. Further studies have shown that 2EN is also an
      efficient mechanism-based inactivator of the 7-ethoxycoumarin O-deethylase
      activity of rabbit P450 2B4 with 0.83 mol of adduct bound per mole of P450.
      Cleavage of [3H]2EN-inactivated 2B1 with cyanogen bromide, separation of the
      peptides by HPLC, and further purification of the radiolabeled fraction by
      Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) led
      to the identification by autoradiography of a radiolabeled peptide (M(r)
      approximately 3000). Amino acid sequence analysis of the first 12 N-terminal
      residues revealed the sequence ISLLSLFFAGTE corresponding to positions 290-301 in
      the protein. When the radiolabeled fraction from the HPLC separation was analyzed
      by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS),
      peaks at m/z 2722.5 and 2890.6 were detected. The lower mass peak corresponds to
      the molecular ion (average mass) of the cyanogen bromide peptide Ile290 to Met314
      (theoretical 2722.2), while the higher mass peak corresponds to the same peptide
      with a bound 2-naphthylacetyl group (theoretical 2890.4). When [3H]2EN
      inactivated 2B4 was treated with cyanogen bromide, the peptides were separated by
      HPLC, and the fractions were analyzed by Tricine-SDS-PAGE, two radiolabeled
      peptides (M(r) = 5000 and 8000) were identified by autoradiography. Amino acid
      sequence analysis of the first 11 residues revealed identical N-termini with the
      sequence EKDKSDPSSEF corresponding to positions 273-283.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8142378
TI  - Photolabeling of mitochondrial F1-H+ATPase by 2-azido[3H]ADP and 8-azido[3H]ADP
      entrapped as fluorometal complexes into the catalytic sites of the enzyme.
AB  - In the presence of ADP and fluorometals, the ATPase activity of the catalytic
      sector, F1, of beef heart mitochondrial ATPase is strongly inhibited; this
      inhibition is dependent on the entrapment of ADP-fluoroaluminate complexes into
      the nucleotide binding sites of F1 [Lunardi, J., Dupuis, A., Garin, J., Issartel,
      J. P., Michel, L., Chabre, M., & Vignais, P. V. (1988) Proc. Natl. Acad. Sci.
      U.S.A. 85, 8958-8962]. We described here the effect of fluoroaluminate on the
      binding of 2-azido[3H]ADP and 8-azido[3H]ADP to beef heart mitochondrial F1 in
      the absence and presence of light. When the incubation medium was supplemented
      with NaF and AlCl3, and maintained in the dark, both 2-azido[3H]ADP and 8
      azido[3H]ADP were able to elicit inhibition of F1-ATPase activity, exactly like
      ADP did. Upon photoirradiation, 2-azido[3H]ADP and 8-azido[3H]ADP bound
      covalently to F1. Labeling was restricted to the beta subunit of F1, and the same
      tyrosine residue, beta-Tyr-345, was labeled by either of the photoprobes. This is
      in contrast with the previous findings that in the absence of fluoroaluminate
      both the alpha and beta subunits of F1 were photolabeled by 8-azido[3H]ADP, and
      that two different regions of the beta subunits were labeled, centered on beta
      Tyr-345 in the case of 2-azido[3H]ADP [Garin, J., Boulay, F., Issartel, J.P.,
      Lunardi, J., & Vignais, P. V. (1986) Biochemistry 25, 4431-4437] and beta-Tyr-311
      that of 8-azido[3H]ADP [Hollemans, M., Runswick, M., Fearnley, I.H., & Walker,
      J.E. (1983) J. Biol. Chem. 258, 9307-9313].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142379
TI  - Folding of barnase in parts.
AB  - Stretches of residual structure in the unfolded states of proteins could possibly
      constitute crucial regions that initiate protein folding. We are searching for
      such regions in barnase by dividing it into fragments. By this means, we can
      search for regions that just form within local sequences. We are also employing
      methods that can detect low levels of residual structure. In this study, we
      examine the fragment 1-22 and a large fragment (23-110) that contains all of the
      catalytic residues. Fragment 1-22 contains the first alpha-helix, and fragment 23
      110 contains the second alpha-helix and beta-sheet structure-forming residues of
      native barnase. These fragments bind together rapidly and tightly upon
      association to form a fully native-like complex. Studies by circular dichroism
      and fluorescence spectroscopy indicate that each fragment is mainly disordered.
      However, we find by a procedure of titration with trifluoroethanol that about 3%
      of fragment 1-22 is helical in water at 25 degrees C. Importantly, we have
      detected residual catalytic activity in fragment 23-110 toward GpUp and RNA and
      the ability to bind the polypeptide inhibitor of barnase, barstar, suggesting
      that this fragment can form a native-like conformation in water. The catalytic
      activity does not result from a small amount of contaminating impurity of parent
      enzyme or other ribonuclease, since the activity requires a 1:1 mole ratio of
      fragment to barstar for complete inhibition, and the activity is lost in much
      lower concentrations of urea than are required to denature the parent enzyme.
      There is a very weak signal in the near-UV CD spectrum of the large
      fragment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142380
TI  - Hydrostatic pressure reverses osmotic pressure effects on the specificity of
      EcoRI-DNA interactions.
AB  - To characterize the role of water in protein-DNA interactions, we have studied
      the specificity of the EcoRI restriction endonuclease as a function of osmotic
      and hydrostatic pressure. The extent of cleavage by the enzyme at noncanonical
      ("star") sites is shown to depend uniquely upon the osmotic pressure in the
      reaction as controlled by the addition of a wide variety of neutral solutes.
      Alteration of cleavage specificity ("EcoRI* activity") is not uniformly
      correlated with any other colligative solvent property such as dielectric
      constant, viscosity, or water concentration. The application of hydrostatic
      pressure reverses the effects of osmotic pressure, restoring the natural
      selectivity of the enzyme for its canonical site GAATTC. This combination of
      observations provides compelling evidence that the site-specific recognition of
      canonical site DNA by EcoRI is mediated by discretely bound water molecules and
      that the release of these waters induces a fundamental change in the specificity
      of the interaction, leading to cleavage at alternative sites. This comprehensive
      analysis of solvent effects facilitates the unambiguous identification of
      structurally and functionally specific waters involved in macromolecular
      recognition events.

PMID- 8142381
TI  - DNA distortion in bis-intercalated complexes.
AB  - The bis-intercalators Flexi-Di and ditercalinium are synthetic dimers that bis
      intercalate into DNA and cause cell death in prokaryotes from futile and abortive
      repair of DNA. Each is composed of two 7H-pyridocarbazole units and a linker.
      Flexi-Di has a flexible spermine-like linker while ditercalinium has a rigid
      bis(ethylpiperidinium) linker. This report, describing the 2.5-A X-ray structure
      of Flexi-Di complexed with [d(BrCGCG)]2, appears to be the first report of a
      three-dimensional structure of a DNA complex with a bis-intercalator with a
      flexible linker. DNA complex formation with a ditercalinium analog having a
      flexible linker was not anticipated to yield unstacked and bent DNA as was
      observed in the previously reported ditercalinium.[d(CGCG)]2 complex.
      Surprisingly, the DNA in the Flexi-Di complex is bent to a degree exceeding that
      of the ditercalinium complex. A comparison of the DNA complexes of Flexi-Di and
      ditercalinium has allowed us to propose a mechanism by which these bis
      intercalators distort DNA. We propose that this class of bis-intercalators pulls
      the internal base pairs into the major groove and pushes the external base pairs
      into the minor groove. The result is a bend toward the minor groove. It appears
      that hydrogen bonds between the linker and the internal guanines effectively pull
      the central base pairs of the complex out into the major groove. At the external
      regions of the complex, stacking interactions between the chromophores and
      terminal base pairs effectively push the terminal base pairs into the minor
      groove. The result of this push/pull combination is to bend the DNA.

PMID- 8142382
TI  - Thymine methyl groups stabilize the putative A-form of the synthetic DNA
      poly(amino2dA-dT).
AB  - Poly(amino2dA-dT) easily isomerizes into a non-B conformer which most authors
      think is an A-form. We synthesized new DNA analogs poly(amino2dA-ethyl5dU) and
      poly(amino2dA-dU) to show that they do not prefer this conformer. Hence the
      putative A-form is, like Z-DNA of poly(dG-dC) but unlike A-DNA, strongly
      stabilized by the methyl group in position 5 of the pyrimidine base. In addition,
      the putative A-form is induced by divalent cations while it does not need any
      alcohol to be stable, both properties being typical for Z-DNA again but quite
      unusual with A-DNA. Despite these similarities, the putative A-form is also
      distinct from Z-DNA, as poly(amino2dA-dT) is shown to isomerize into a Z-form in
      the NaCl + NiCl2 solvent system like poly(dA-dT). The present data indicate that
      the putative A-form of poly(amino2dA-dT) differs in a significant way from all
      canonical conformers of DNA. Furthermore, the studies of the poly(amino2dA-dT)
      family of polydeoxynucleotides reveal a novel type of conformational switch in
      DNA. We also report the B-Z transitions of poly(amino2dA-ethyl5dU) and
      poly(amino2dA-dU) and their transitions into the putative A-form in aqueous
      alcohol solutions.

PMID- 8142383
TI  - Small molecule binding to an artificially created cavity at the active site of
      cytochrome c peroxidase.
AB  - In the oxidized "ES" state of cytochrome c peroxidase, Trp-191 is reversibly
      oxidized to a stable cation free radical by the hypervalent heme. To explore the
      potential for engineering a binding site for heterocyclic compounds at this site,
      the mutant W191G was constructed. Two independent crystal structures of W191G at
      2.1- and 2.3-A resolution show that W191G contains a well-defined, approximately
      180-A3 cavity at the Trp-191 site. The cavity is occupied by five ordered water
      molecules which participate in an extensive hydrogen-bonding network with each
      other, with polar main-chain atoms, and with the carboxylate of Asp-235. After a
      number of heterocyclic compounds were screened, evidence was obtained that
      substituted imidazoles bind to the cavity of W191G. Titration of W191G with
      imidazole resulted in a perturbation of the Soret absorption band that was not
      observed for W191H, W191F, or the native enzyme. The dissociation constants for
      binding of benzimidazole, imidazole, 2-ethylimidazole, 1-methylimidazole, 2
      methylimidazole, and 1,2-dimethylimidazole to W191G were respectively 2.58, 0.70,
      0.36, 0.057, 0.047, and 0.027 mM at pH 6.0. The highest binding affinity was
      exhibited by 1,2-dimethylimidazole, indicating that steric interactions and the
      efficiency of filling the cavity are important determinants for specificity. The
      Kd for imidazole binding increased from 0.7 mM at pH 6 to 3.0 mM at pH 8 and
      could be fit to a single proton ionization curve with a pKa of 7.4, demonstrating
      the preferential binding by the imidazolium ion (pKa = 7.3). The binding of a
      number of substituted imidazoles to the cavity of W191G was verified by X-ray
      crystallographic analysis. The most clearly defined density was observed for
      W191G crystals soaked in 1 mM 1,2-dimethylimidazole and was consistent with an
      oriented occupation in which the unsubstituted nitrogen forms a hydrogen bond or
      ion pair interaction with Asp-235. Thus, enhanced binding of positively charged
      molecules may be the result of interactions with this carboxylate. An analogous
      interaction may stabilize the developing positive charge on the Trp-191 radical
      of the wild-type enzyme. While the oxidation of imidazoles by the ferryl
      intermediate of W191G was neither expected nor observed, this study has defined
      the structural determinants for small molecule binding to an artificially created
      cavity near a heme center which is capable of generating oxidized species at a
      potential of over 1 V, and these results will guide future attempts for novel
      substrate oxidation by CCP.

PMID- 8142384
TI  - Unusual structures of the tandem repetitive DNA sequences located at human
      centromeres.
AB  - The presence of the highly conserved repetitive DNA sequence d(AATGG)n.d(CCATT)n
      in human centromeres argues for a special role for this sequence in recognition,
      most probably through the formation of an unusual structure during mitosis.
      Quantitative one- and two-dimensional nuclear magnetic resonance (1D/2D NMR)
      spectroscopic studies reveal that the Watson-Crick duplex d(AATGG)n.d(CCATT)n
      adopts the usual B-DNA conformation as illustrated by taking d(AATGG)3.d(CCATT)3
      as an example, whereas the d(CCATT)n strand is essentially a random coil. In
      contrast, the d(AATGG)n strand adopts an unusual stem-loop motif for repeat
      lengths n = 2, 3, 4, and 6. In addition to normal Watson-Crick A.T pairs, the
      stem-loop structures are stabilized by mismatched A.G and G.G pairs in the stem
      and G-G-A stacking in the loop. Stem-loop structures of d(AATGG)n are
      independently verified by gel electrophoresis and nuclease digestion studies and
      were also previously shown to be as stable as the corresponding Watson-Crick
      duplex d(AATGG)n.d(CCATT)n [Grady et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89,
      1695-1699]. Therefore, the sequence d(AATGG)n can, indeed, nucleate a stem-loop
      structure at little free energy cost, and if, during mitosis, it is located on
      the chromosome surface, it can provide specific recognition sites for kinetochore
      function.

PMID- 8142385
TI  - Energetic characterization of the basic fibroblast growth factor-heparin
      interaction: identification of the heparin binding domain.
AB  - Fibroblast growth factors (FGF's) interact on cell surfaces with "low-affinity"
      heparan sulfate proteoglycans (HSPG) and "high-affinity" FGF receptors (FGFR) to
      initiate cell proliferation. Previous reports have implicated the binding of
      heparin, or heparan sulfate, to FGF as essential for FGF-mediated signal
      transduction and mitogenicity. However, the molecular recognition events which
      dictate the specificity of this interaction have remained elusive. Amino acid
      residues on the surface of basic FGF (bFGF) were targeted as potential heparin
      contacts on the basis of the position of sulfate anions in the X-ray crystal
      structure of bFGF and of a modeled pentasaccharide heparin-bFGF complex. Each
      identified amino acid was replaced individually with alanine by site-directed
      mutagenesis, and the resulting mutant proteins were characterized for differences
      in binding to a low molecular weight heparin (approximately 3000) by isothermal
      titrating calorimetry and also for differences in [NaCl] elution from a heparin
      Sepharose affinity resin. The combination of site-directed mutagenesis and
      titrating calorimetry permitted an analysis of the energetic contributions of
      individual bFGF residues in the binding of heparin to bFGF. The key amino acids
      which comprise the heparin binding domain on bFGF constitute a discontinuous
      binding epitope and include K26, N27, R81, K119, R120, T121, Q123, K125, K129,
      Q134, and K135. Addition of the observed delta delta G degrees of binding for
      each single site mutant accounts for 8.56 kcal/mol (> 95%) of the free energy of
      binding. The delta delta G degrees values for N27A, R120A, K125A, and Q134A are
      all greater than 1 kcal/mol each, and these four amino acids together contribute
      4.8 kcal/mol (56%) to the total binding free energy. Amino acid residues K119
      through K135 reside in the C-terminal domain of bFGF and collectively contribute
      6.6 kcal/mol (76%) of the binding free energy. Although 7 out of the 11
      identified amino acids in the heparin binding domain are positively charged, a 7
      fold increase in [NaCl] decreases the affinity of wild-type bFGF binding to
      heparin only 37-fold (Kd at 0.1 M NaCl = 470 nM vs Kd at 0.7 M NaCl = 17.2
      microM). This indicates that pure electrostatic interactions contribute only 30%
      of the binding free energy as analyzed by polyelectrolyte theory and that more
      specific nonionic interactions, such as hydrogen bonding and van der Waals
      packing, contribute the majority of the free energy for this binding reaction.

PMID- 8142386
TI  - Xenopus laevis ovarian DNA helicase I: A 3' to 5' helicase that unwinds short
      duplexes.
AB  - A novel DNA helicase isolated from Xenopus laevis ovaries [Poll, E. H. A., &
      Benbow, R. M. (1988) Biochemistry 27, 8701-8706] was characterized biochemically.
      The directionality of DNA unwinding was determined to be 3' to 5'. A short 3'
      ssDNA tail adjacent to duplex DNA was required for DNA unwinding; the minimum
      length of this tail was between four and nine bases. Only short duplex DNA
      regions were unwound: duplex DNA of 16 base pairs was readily unwound, whereas a
      26 base pair duplex was not. Longer duplex regions were unwound in the presence
      of Escherichia coli single-strand DNA binding protein if, in addition, the duplex
      region was flanked by an unpaired 3' or 5' tail and the substrate resembled a
      branched replicative intermediate. X. laevis DNA helicase I exhibited high
      affinity for ssDNA, moderate affinity for dsDNA, and no affinity for RNA. DNA
      unwinding activity was stimulated by monovalent cations, with an optimal
      concentration of 150 mM for NaCl or KCl or 125 mM for Na chi PO4 or K chi PO4.
      The ATP analog ATP gamma S inhibited the DNA unwinding and copurifying DNA
      dependent ATPase activity, whereas AMPPCP and AMPPNP moderately inhibited DNA
      unwinding activity and had little effect on the copurifying DNA-dependent ATPase
      activity. CTP was a relatively strong inhibitor of DNA unwinding activity, but
      GTP, UTP, dCTP, dGTP, or TTP showed moderate or no inhibition. The copurifying
      DNA-dependent ATPase activity was not inhibited by CTP, GTP, UTP, dCTP, dGTP, or
      TTP.

PMID- 8142387
TI  - Hybridization of a complementary ribooligonucleotide to the transcription start
      site of the lacUV-5-Escherichia coli RNA polymerase open complex. Potential for
      gene-specific inactivation reagents.
AB  - An ribooligonucleotide, UGGAA, complementary to the template strand of the lacUV
      5 promoter can hybridize to the transcription "bubble" of the open complex formed
      by Escherichia coli RNA polymerase. Its site-specific binding, measured by gel
      retardation, enzyme inhibition, and chemical nuclease footprinting, is dependent
      on catalysis by RNA polymerase and the sequence of the hybridizing
      ribooligonucleotide. When UGGAA is linked to the chemical nuclease 1,10
      phenanthroline copper, site-specific scission of the template strand of the
      transcriptionally active gene is observed. The formation of single-stranded DNA
      at transcription start sites by RNA polymerases provides a target for antigene
      strategies.

PMID- 8142388
TI  - Mobility and orientation of spin probes attached to nucleotides incorporated into
      actin.
AB  - Each actin molecule contains a nucleotide, tightly bound in a deep cleft that
      divides the molecule. To probe conformational changes within this region of the
      molecule, we have incorporated two spin label analogues of ATP into actin. In
      both analogs the spin label was attached to the 6 position on the adenine ring,
      either directly (6nSLATP) or via a longer thioacetamido linker (6sSLATP).
      Electron paramagnetic resonance spectra of randomly oriented actin filaments
      showed that both the probes possessed considerable rotational mobility relative
      to the protein surface. The 6nSLADP has two degrees of rotational mobility that
      can be approximately modeled by rapid diffusion within cones with half angles of
      30 +/- 1 degrees and 42 +/- 1.5 degrees. The 6sSLADP displayed one degree of
      rotational mobility approximated by rapid motion within a cone with a half-angle
      of 38 +/- 1 degrees. The rotational mobility of the probes is determined by the
      protein structure surrounding them, and changes in this structure should alter
      the mobility. The mobility of the probes was unchanged by addition of 20 mM Pi,
      which forms an ADP-Pi complex. However, binding of myosin heads (S1) shifted the
      population of 6nSLADP toward the more highly restricted cone, while binding of
      DNase-I shifted it toward the less restricted cone. We conclude that this region
      of actin is unchanged by binding of phosphate, while the binding of S1 or DNase-I
      produces only a modest shift in conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142389
TI  - Electrostatic interactions control the parallel and antiparallel orientation of
      alpha-helical chains in two-stranded alpha-helical coiled-coils.
AB  - The role of interchain electrostatic interactions in orientating alpha-helical
      chains to form two-stranded parallel and antiparallel coiled-coils has been
      investigated. Four disulfide-bridged coiled-coils were designed: parallel coiled
      coils with interchain electrostatic attractions (P/A) and repulsions (P/R) and
      antiparallel coiled-coils with interchain electrostatic attractions (AP/A) and
      repulsions (AP/R). These coiled-coils were made by air oxidation of two 35
      residue peptides with the appropriate heptad repeat (LaEbAcLdEeGfKg or
      LaAbEcLdKeGfEg) to give the desired interchain electrostatic interactions, and
      the appropriate position of the cysteine residue (C2 or C33) to give the desired
      chain orientation. The coiled-coils were characterized by circular dichroism
      spectroscopy, and their stabilities were assessed by guanidine hydrochloride and
      urea denaturations. The results indicated that the favored chain orientation,
      that is, the major disulfide-bridged product formed under benign conditions, was
      the one that provides interchain electrostatic attractions between oppositely
      charged amino acid residues in the e-g' and g-e' positions of the parallel coiled
      coil and the g-g' and e-e' positions in the antiparallel coiled-coil. When the
      electrostatic interactions were similar, the antiparallel coiled-coils were more
      stable than the parallel coiled-coils. However, the overall stability of the
      coiled-coils was either increased by interchain electrostatic attractions or
      decreased by interchain electrostatic repulsions, as determined by urea
      denaturation. Thus, the order of overall stability of these coiled-coils was AP/A
      > P/A > AP/R > P/R. This study demonstrates the importance of interchain
      electrostatic interactions in determining the parallel or antiparallel
      orientation of alpha-helical chains in two-stranded coiled-coils.

PMID- 8142390
TI  - Site-directed mutagenesis of kappa-bungarotoxin: implications for neuronal
      receptor specificity.
AB  - Postsynaptic polypeptide neurotoxins isolated from the venoms of elapid and
      hydrophid snakes exhibit the ability to bind selectively to and inhibit different
      types of receptors that function in nerve signal transmission. On the basis of
      their amino acid sequences and three-dimensional structures, these neurotoxins
      are clearly related, but nothing is yet known about the basis for their
      physiological receptor specificity. In this report, site-directed mutants of
      kappa-bungarotoxin, produced by an Escherichia coli expression system, are tested
      to determine the function of selected amino acid side chains in the interaction
      between toxin and receptor. Highly conserved residues at the bottom of the second
      loop (a region that has been shown to be a major point of contact with the
      receptor), particularly those residues at the junction between the beta-sheet and
      the end of the loop, were selected. The results demonstrate that a single amino
      acid substitution of the invariant arginine residue (Arg-40 to Ala-40) renders
      the toxin unable to inhibit nerve transmission in the chick ciliary ganglion up
      to a concentration of 10 microM. Significantly, the results also show that
      conversion to alanine of the nearby proline residue (Pro-42) found to be
      invariant in all kappa-neurotoxins, but not found in any potent alpha-neurotoxin,
      produces a toxin with full inhibitory capacity. However, the introduction of a
      lysine residue at this position (P-42-K), like that found in alpha-bungarotoxin,
      reduces activity significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142391
TI  - Cross-linking of mRNA analogues containing 4-thiouridine residues on the 3'- or
      5'-side of the coding triplet to the mRNA binding center of the human ribosome.
AB  - The interaction between mRNA and 18S rRNA within complexes of human placenta 80S
      ribosomes has been investigated by photochemical cross-linking experiments using
      mRNA analogues substituted with 4-thiouridine at specific locations. mRNA
      analogues 51 or 54 nucleotides long were prepared from synthetic DNA templates.
      These mRNA analogues contained either the sequence GGGACC (coding for glycine and
      threonine, respectively) or the single triplet GGG together with 2-4 4
      thiouridine residues located at various positions with respect to the coding
      triplets. The products of cross-linking of the mRNA analogues to 18S rRNA within
      different model complexes without tRNA or in the presence of cognate tRNAs were
      analyzed by reverse transcription. Two cross-linking sites in the 18S rRNA were
      detected. The first site, U630, was cross-linked by mRNA 8' (s4U at +20, +22,
      +24, and +26), mRNA 9e' (s4U at -16, -18, and -20), and mRNA 10 (s4U at +4, +6, 
      1, and -3) but, unexpectedly, not with either mRNA 10b (s4U at +4 and +6) or mRNA
      10c (s4U at -1 and -3). The second site, U1111/A1112, was cross-linked by mRNA 10
      and mRNA 10c but not by any of the other mRNA analogues. There is significant
      tRNA dependence on cross-linking only for mRNA analogue 9e'. Both of the sites
      detected correspond to sites of mRNA cross-linking in Escherichia coli 16S rRNA.

PMID- 8142392
TI  - Site-specific O-glycosylation of cell adhesive lysozyme in yeast.
AB  - The cell adhesive protein RGD8 has been constructed using a yeast expression
      system by inserting eight amino acid residues (TGRGDSPA) between Val74 and Asn75
      of human lysozyme [Yamada et al. (1993) J. Biol. Chem. 268, 10588-10592].
      Purified RGD8 from yeast culture supernatant was found to contain glycosylated
      variants, in addition to the unglycosylated form. Peptide mapping analyses
      suggested that the glycosylation occurred at the inserted Thr residue in the RGD8
      molecule. Electrospray ionization mass spectrometric analysis demonstrated the
      presence of four or five hexose residues in the glycosylated variants. Only
      mannose was detected in the sugar analysis of the oligosaccharide mixture
      obtained by mild alkaline treatment of the variants, and the structures of these
      carbohydrate chains were identified as Man alpha 1-3Man alpha 1-2Man alpha 1-2Man
      alpha and Man alpha 1-3Man alpha 1-3Man alpha 1-2Man alpha 1-2Man alpha by 1H-NMR
      spectroscopy. No other glycosylation was found, although the RGD8 molecule
      possesses a total of 13 Thr and Ser residues. In addition, no O-glycosylation was
      observed when the RGD8 protein was expressed in mouse L-cells. Thus, this O
      glycosylation looks specific for yeast and the site of the Thr residue. The O
      glycosylated variants of RGD8 exhibited a high level of adhesion activity to baby
      hamster kidney cells, which was almost comparable to that of the unglycosylated
      form.

PMID- 8142393
TI  - Cleavage of double-crossover molecules by T4 endonuclease VII.
AB  - DNA double-crossover molecules containing two Holliday junctions have been
      prepared and treated with endonuclease VII, the resolvase from bacteriophage T4.
      One molecule contains antiparallel double-helical domains, and the other molecule
      contains parallel domains. The parallel double-crossover model system has been
      made tractable by closing the free ends of the molecule, to convert it to a
      catenane. The products resulting from the two substrates differ substantially.
      The molecule containing antiparallel helical domains is cleaved three nucleotides
      3' to the crossover points, in a fashion similar to single Holliday junction
      analogs. The molecule containing parallel helical domains is cleaved, but the
      major points of scission are five nucleotides 5' to a branch point on the
      crossover strands and six nucleotides 3' to the same branch point on the non
      crossover strands. The major sites of scission reflect features of molecular
      symmetry in each case, suggesting that the resolvase recognizes structural
      features. The cleavage results suggest that the antiparallel structure is the
      natural substrate, if the Holliday junction is unconstrained within the cell. It
      is straightforward to reconcile antiparallel Holliday junctions with the
      conventional parallel paradigm of recombination. Nevertheless, the cleavage of
      the parallel molecule shows that a parallel substrate could also be cleaved
      symmetrically by endonuclease VII (but with different products) if the molecule
      were constrained to assume that conformation within the cell.

PMID- 8142394
TI  - Involvement of the gamma-phosphate of UTP in the synergistic inhibition of
      Escherichia coli aspartate transcarbamylase by CTP and UTP.
AB  - The allosteric control of Escherichia coli aspartate transcarbamylase (ATCase)
      involves synergistic feedback inhibition by CTP and UTP. Previously reported
      results [England, P., & Herve, G. (1992) Biochemistry 31, 9725-9732] suggest that
      this phenomenon relies entirely on interactions between the two neighboring
      allosteric sites, which belong to the same regulatory dimer. Furthermore, it has
      been demonstrated that UTP alone binds to the enzyme, but that it is only in the
      presence of CTP that this binding inhibits the catalytic activity. The properties
      of mutants in which the synergistic inhibition is totally abolished suggested
      that the terminal gamma-phosphate of the pyrimidine triphosphate nucleotides may
      play a crucial role in promoting site-site interactions within the regulatory
      dimer. In the present work, kinetic studies and binding experiments by continuous
      flow dialysis were performed, using combinations of diphosphate and triphosphate
      nucleotides. The results obtained show that the gamma-phosphate lf UTP is indeed
      essential for synergistic inhibition to occur, as UDP is unable to inhibit ATCase
      activity, whether alone or in combination with CTP. On the contrary, the gamma
      phosphate of CTP can be suppressed without modifying the inhibitory properties of
      this nucleotide and its synergy of action with UTP. These results indicate that
      the mutual effects of CTP and UTP on their respective binding are not symmetrical
      and that the signals emitted upon binding of the two triphosphate pyrimidine
      nucleotides to the regulatory sites do not follow the same pathway and involve
      different mechanisms.

PMID- 8142395
TI  - A calorimetric study of the thermal stability of barnase and its interaction with
      3'GMP.
AB  - We have used high-sensitivity differential scanning calorimetry to characterize
      the thermal stability of barnase from Bacillus amyloliquefaciens in the pH range
      2.0-5.0. The energetics of the interaction between barnase and its inhibitor
      3'GMP have been studied by isothermal titration calorimetry in the temperature
      range 15-30 degrees C. Scanning calorimetry experiments were also made with the
      protein in the presence of various concentrations of 3'GMP at pH 4.5. A novel,
      simple procedure is proposed to obtain binding parameters from scanning
      calorimetry data. This method is based on the calculation of the partition
      functions of the free and the ligand-bound protein. Isothermal calorimetry shows
      that at 25 degrees C 3'GMP binds to a single site in barnase with a delta Cp of 
      250 +/- 50 J/(K.mol). Both free barnase and ligand-bound barnase undergo a highly
      reversible, two-state thermal unfolding process under our experimental
      conditions. delta G and delta Cp unfolding values are similar to others found for
      globular proteins, whereas delta H and delta S unfolding values are unusually
      high at the denaturation temperature of barnase. We have also found unexpectedly
      that the thermodynamic unfolding parameters of barnase fit neither the trend of
      values described in the literature for the correlation between delta Cp and delta
      H nor the limiting specific enthalpy value in the correlation between delta H and
      Tm for globular proteins. These discrepancies might be related to particular
      features of the folded and/or unfolded states of the protein.

PMID- 8142396
TI  - Effects of phorbol myristate acetate on the synthesis of 5-oxo-6,8,11,14
      eicosatetraenoic acid by human polymorphonuclear leukocytes.
AB  - 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a newly discovered
      chemotactic agent for human polymorphonuclear leukocytes (PMNL) which has potent
      stimulatory effects on cytosolic calcium levels in these cells. Although we have
      shown that it is synthesized from 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5
      HETE) by a highly specific microsomal dehydrogenase, little is known about the
      synthesis of this substance by intact PMNL. In the present study we found that in
      contrast to PMNL microsomes, intact, unstimulated PMNL produced relatively small
      amounts of 5-oxo-ETE from 5-HETE, but instead converted 5-HETE primarily to its
      omega-oxidation product, 5,20-diHETE. However, preincubation of PMNL with phorbol
      myristate acetate (PMA; EC50, ca. 4 nM) dramatically increased the ratio of 5-oxo
      ETE to 5,20-diHETE from 0.07 in its absence to 1.85 in the presence of 100 nM
      PMA. Both effects were completely reversed by staurosporine, indicated that they
      were mediated by a protein kinase. PMA also stimulated the formation of 5-oxo
      ETE, 5-HETE, and leukotriene B4 (LTB4) from exogenous arachidonic acid. The
      greatest enhancement was observed for 5-oxo-ETE, which, under all conditions, was
      produced in greater quantities than LTB4. PMA stimulated the formation of 5-oxo
      ETE by PMNL stimulated with either A23187 or zymosan. A23187-stimulated PMNL
      initially produced more LTB4 than 5-oxo-ETE, but at longer time points, 5-oxo-ETE
      predominated. These results demonstrate that PMA-activated human PMNL can
      synthesize substantial amounts of 5-oxo-ETE and raise the possibility that this
      substance may be an important inflammatory mediator.

PMID- 8142397
TI  - Inactivation of interleukin-1 beta converting enzyme by peptide (acyloxy)methyl
      ketones.
AB  - Interleukin-1 beta converting enzyme (ICE) is a cysteine protease in monocytes
      that is essential for the proteolytic activation of interleukin-1 beta, an
      important mediator of inflammation. Peptide (acyloxy)methyl ketones designed with
      the appropriate peptide recognition sequence (Ac-Tyr-Val-Ala-Asp-CH2-OC(O)Ar) are
      potent, competitive, irreversible inhibitors. Mass spectrometry and sequence
      analysis indicate that inactivation proceeds through expulsion of the carboxylate
      leaving group to form a thiomethyl ketone with the active site Cys285. The second
      order inactivation rate is independent of leaving group pKa, with an approximate
      value of 1 x 10(6) M-1 s-1. This rate constant is directly proportional to the
      reaction macroviscosity, indicating that the rate-limiting step in inactivation
      is association of enzyme and inhibitor, rather than any bond-forming reactions.
      Affinity labeling of THP.1 monocytic cell cytosol with a biotinylated
      tetrapeptide (acyloxy)methyl ketone for 28 half-lives resulted in labeling of
      only ICE, demonstrating the selectivity of these inhibitors. These inhibitors are
      relatively inert toward other bionucleophiles such as glutathione (< 5 x 10(-4) M
      1 s-1), making them excellent candidates for in vivo studies of enzyme
      inhibition.

PMID- 8142398
TI  - Ca(2+)-dependent 68-kilodalton protease in familial Alzheimer's disease cells
      cleaves the N-terminus of beta-amyloid.
AB  - Lymphoblastoid cells derived from patients with early- and late-onset familial
      Alzheimer's disease express a Ca(2+)-dependent, 68-kDa protease which forms an
      SDS-stable and heat-labile complex with the beta-amyloid precursor protein.
      Utilizing this property, we prepared the protein by heat-dissociation of its
      immunoprecipitate with an antibody raised against the extracellular part of the
      beta-amyloid precursor protein. Disuccinimidyl suberate cross-linking analysis
      showed that in the presence of Ca2+ this protein binds to a synthetic
      oligopeptide corresponding to the first 12 amino acids of beta/A4-amyloid and its
      N-terminal flanks. Thin-layer chromatography of a reaction mixture of the 68-kDa
      protein and the oligopeptide demonstrated its proteolytic activity in the
      presence of Ca2+. Subsequent N-terminal amino acid sequencing of the cleaved
      fragment showed the cleavage site of the oligopeptide to be the Lys-2-Met-1-Asp
      beta A4-1 bonds. This protease also cleaves a natural substrate of 110-kDa beta
      amyloid precursor protein, thereby generating the 16-kDa preamyloid peptide that
      accumulates abnormally in familial Alzheimer's disease lymphoblastoid cells. It
      does not, however, cleave the Gln beta A4-15-Lys16-Leu17 bond that is regarded to
      be the normal proteolytic site for the secretion of the beta-amyloid precursor
      protein. Analysis of the effects of protease inhibitors suggests that this 68-kDa
      protease is a Ca(2+)-dependent serine protease.

PMID- 8142399
TI  - Ecotin is a potent anticoagulant and reversible tight-binding inhibitor of factor
      Xa.
AB  - Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli,
      has been characterized as an extremely potent anticoagulant and reversible tight
      binding inhibitor of human factor Xa (FXa). The ecotin gene was cloned by PCR,
      highly expressed in E. coli, and purified from the E. coli periplasm. The binding
      of ecotin to FXa was stoichiometric with an equilibrium dissociation constant Ki
      of 54 pM. The association rate constant was 1.35 x 10(6) M-1 s-1, and the
      dissociation rate constant, measured in the presence of human leukocyte elastase
      (HLE) to prevent reassociation of ecotin with FXa, was 6.5 x 10(-5) s-1. Ecotin
      prolonged clotting time ca. 10-fold at 0.3 microM and at 2 microM in activated
      partial thromboplastin time and prothrombin time assays, respectively. Ecotin did
      not effectively inhibit the human plasma proteases thrombin, tissue factor.factor
      VIIa, factor XIa, activated protein C, plasmin, or tissue plasminogen activator
      (t-PA); however, it did potently inhibit factor XIIa, plasma kallikrein, HLE, and
      bovine trypsin and chymotrypsin. Coincubation of ecotin and FXa at 10 microM each
      resulted in a (ecotin)2.(FXa)2 complex as determined by gel filtration.
      Dimerization of ecotin alone was measured by fluorescence titration which yielded
      a Kd of ca. 390 nM. FXa cleaved ecotin slowly at pH 4.0 between M84 and M85.
      Replacement of the P1 Met84 residue with Arg and Lys led to FXa inhibitors with
      Ki values of 11 and 21 pM, respectively. The P1 Arg and Lys mutants also
      significantly inhibited thrombin, factor XIa, activated protein C, plasmin,
      factor XIIa, kallikrein, and bovine trypsin and chymotrypsin but did not inhibit
      tissue factor.factor VIIa, t-PA, or HLE.

PMID- 8142400
TI  - Mapping of the thrombin des-ETW conformation by using site-directed mutants of
      hirudin. Evidence for the induction of nonlocal modifications by mutagenesis.
AB  - Deletion of Glu146, Thr147, and Trp148 from thrombin dramatically alters its
      interactions with substrates, ligands, and inhibitors, and the changes appear to
      result from nonlocal modification of thrombin's structure [Le Bonniec, B. F.,
      Guinto, E. R., & Esmon, C. T. (1992) J. Biol. Chem. 267, 19341-19348]. In an
      attempt to localize conformational change in this thrombin mutant (des-ETW), its
      affinity for 43 site-directed mutants of hirudin have been compared with that of
      native thrombin. The inhibition constants (KI) of recombinant and natural hirudin
      with des-ETW were found to be approximately 2300-fold higher than those with
      thrombin. The reduced affinity was predominantly the result of an increase in the
      dissociation rate constant rather than a decrease in the association rate
      constant. For most of the hirudin mutants tested, the difference in binding
      energy between thrombin and des-ETW [delta delta Gbo(IIa-ETW)] was about 19.9 kJ
      mol-1 and comparable to that of hirudin; in particular, all mutations in the C
      terminal region of the inhibitor did not affect delta delta Gbo(IIa-ETW). Thus,
      the conformation of thrombin's anion-binding exosite seems unaltered by the des
      ETW mutation. In contrast, hirudin substitutions involving Val1', Val2', Thr4',
      Asp5', and Ser19', as well as the addition of an N-terminal glycine, resulted in
      values of delta delta Gbo(IIa-ETW) which were 2 to 10 kJ mol-1 lower than that
      for hirudin. Furthermore, a Leu15'-->Ala hirudin mutant behaved with des-ETW, as
      a partial competitive inhibitor rather than a tight-binding inhibitor, in
      contrast to all other hirudin variants tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142401
TI  - The dioxygenation rate in lipoxygenase catalysis is determined by the amount of
      iron (III) lipoxygenase in solution.
AB  - The dioxygenation rate in reactions catalyzed by lipoxygenase-1 from soybeans has
      been measured as a function of the enzyme present in the Fe(III) form with rapid
      kinetic techniques. The experiments were carried out at pH 10, 25 degree C. The
      product concentration and the fraction of iron (III) lipoxygenase were monitored
      by measuring the absorbance at 243 nm and the tryptophan fluorescence at 330 nm
      (excitation at 287 nm), respectively. In reactions started with 1.3 microM iron
      (II) lipoxygenase and 9 microM linoleate, the initial rate, r(init) (estimated
      from the increase in absorbance over the initial 0.02 s of the reaction), is very
      small (4 s-1). In contrast, when the reactions are started with 1.3 microM (III)
      lipoxygenase, r(init) is large (150 s-1). In reactions started with mixtures of
      iron(II) and iron(III) lipoxygenase, r(init) is linearly related to the initial
      concentration of the Fe (III) enzyme form. Redistributions of the Fe(II) and
      Fe(III) enzyme forms during the reaction with 12 nM enzyme and 10, 50, or 100
      microM linoleate appear to be directly reflected in changes in the dioxygenation
      rate. The observations provide solid evidence for the hypothesis that only iron
      (III) lipoxygenase can catalyze the hydrogen abstraction step in the
      dioxygenation reaction, and thus can be regarded as the active enzyme species.
      The observed dynamics are accurately predicted by a nonallosteric, two-step model
      for lipoxygenase catalysis [Schilstra et al. (1992) Biochemistry 31, 7692-7699].

PMID- 8142402
TI  - Dynamics of lactose permease of Escherichia coli determined by site-directed
      fluorescence labeling.
AB  - Recently we described the use of site-directed pyrene labeling of engineered
      lactose permease containing paired Cys residues to obtain proximity relationships
      between helices in the C-terminal half of the molecule [Jung, K., Jung, H., Wu,
      J., Prive, G. G., & Kaback, H.R. (1993) Biochemistry 32, 12273]. Pyrene excimer
      fluorescence was detected for the double Cys mutants His322-->Cys/Glu325-->Cys,
      Arg302-->Cys/Glu325-->Cys, and Glu269-->Cys/His322-->Cys, indicating that helix X
      (His322-->Cys/Glu325-->Cys) is in an alpha-helical conformation and that helices
      VIII (Glu269-->Cys) and IX (Arg302-->Cys) are close to helix X (His322-->Cys and
      Glu325-->Cys). In this report, these interactions are used to study dynamic
      aspects of the permease. Excimer fluorescence between helices VIII and X or
      helices IX and X is markedly diminished by sodium dodecyl sulfate, while the
      excimer observed within helix X is unaffected, suggesting that tertiary
      interactions are disrupted by the denaturant with little effect on secondary
      structure. Furthermore, excimer fluorescence observed between helices VIII
      (Glu269-->Cys) and helix X (His322-->Cys) is quenched by Tl+, and the effect is
      markedly and specifically attenuated by ligands of the permease, suggesting that
      the pyrene becomes less accessible to the aqueous phase. The reactivity of single
      Cys residues at positions 269 or 322 was also examined by studying the rate of
      increase in fluorescence with N-(l-pyrenyl)maleimide. With both mutants, ligands
      of the permease cause a dramatic increase in reactivity which is consistent with
      the notion that these positions are transferred into a more hydrophobic
      environment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142403
TI  - H2-forming N5, N10-methylenetetrahydromethanopterin dehydrogenase from
      Methanobacterium thermoautotrophicum catalyzes a stereoselective hydride transfer
      as determined by two-dimensional NMR spectroscopy.
AB  - 5,6,7,8-Tetrahydromethanopterin is a coenzyme playing a key role in the energy
      metabolism of methanogenic archaea. In Methanobacterium thermoautotrophicum, the
      reduction of N5, N10-methenyl-5,6,7,8-tetrahydromethanopterin at C(14a) with H2
      to N5, N10-methylene-5,6,7,8-tetrahydromethanopterin can be catalyzed by H2
      forming methylenetetrahydromethanopterin dehydrogenase, a new hydrogenase present
      in most methanogenic archaea, which is unique because it does not contain nickel
      or iron/sulfur clusters. In this work, the stereochemistry of this enzymatic
      hydride-transfer reaction is elucidated by means of a series of heteronuclear two
      dimensional NMR experiments. It is found that the hydride from H2 is transferred
      by the enzyme into the rel-(pro-R) position of the C(14a) methylene group of the
      reaction product N5, N10-methylene-5,6,7,8-tetrahydromethanopterin. NMR
      experiments are described that show that the hydrogen nucleus of the hydride
      transferred to the oxidized coenzyme partially originates from water. The
      stereochemical course of this reaction is the same as that for direct hydride
      transfer. It is demonstrated that the diastereotopic atoms at C(14a) of the
      reaction product epimerize in an uncatalyzed reaction under the conditions of
      operation of the enzyme (k = 0.01 s-1 at 58 degree C and pH 6.5).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8142404
TI  - Amidrazone analogues of D-ribofuranose as transition-state inhibitors of
      nucleoside hydrolase.
AB  - The transition state of inosine during hydrolysis by nucleoside hydrolase has
      been characterized by kinetic isotope effects, bond-energy/bond-order vibrational
      analysis, and molecular electrostatic potential surface calculations [Horenstein,
      B. A., Parkin, D. W., Estupinan, B., & Schramm, V. L. (1991) Biochemistry 30,
      10788-10795; Horenstein, B. A., & Schramm, V. L. (1993) Biochemistry 32, 7089
      7097]. The heterocyclic base is protonated and the anomeric carbon of the
      ribofuranosyl ring is flattened to form a transition-state with extensive
      oxocarbenium ion character. With their delocalized charge and flattened
      structures, amidrazone analogues of D-ribofuranose provide both geometric and
      electronic mimics of the ribosyl group at the transition-state of nucleoside
      hydrolase. A family of riboamidrazones was synthesized with H, phenyl, and p
      nitrophenyl N-substituents. The analogues were competitive inhibitors with
      respect to inosine and gave Ki values of 10(-5), 2 x 10(-7), and 1 x 10(-8) M,
      respectively. (p-Nitrophenyl)riboamidrazone exhibited slow-onset, tight-binding
      inhibition, with an overall dissociation constant of 2 x 10(-9) M. The binding is
      reversible with an off-rate of 3 x 10(-3) s-1. Tight binding can be attributed to
      the close spatial match between the molecular geometry of (p
      nitrophenyl)riboamidrazone and the transition-state stabilized by nucleoside
      hydrolase. The favorable binding interactions of the (p
      nitrophenyl)riboamidrazone include oxocarbenium ion mimicry, isosteric ribosyl
      hydroxyls, and hydrophobic and H-bonding interactions at the nitrophenyl
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142405
TI  - Complete heme proton hyperfine resonance assignments of the Glycera dibranchiata
      component IV metcyano monomer hemoglobin.
AB  - Monomer hemoglobin component IV is one of three major myoglobin-like proteins
      found in the erythrocytes of the marine annelid Glycera dibranchiata. Unlike
      myoglobin, all three of these monomer hemoglobin components lack the distal
      histidine, which is replaced by leucine. This substitution alters the protein's
      functional properties due to its proximity to the heme ligand binding site. As
      the initial step toward a full NMR characterization of this protein, a complete
      set of self-consistent proton NMR assignments for the heme and the proximal
      histidine of the paramagnetic, metcyano form of native component IV (metGMH4CN)
      is presented. These assignments relied upon a combination of one- and two
      dimensional NMR spectroscopy, including nonselective spin-lattice relaxation time
      measurements. The metcyano form has been chosen for several reasons: (1) The heme
      paramagnetism acts as an intrinsic shift reagent which aids in making individual
      resonance assignments for the heme and neighboring amino acids in the protein's
      ligand binding site. (2) Heme paramagnetism also enhances proton nuclear
      relaxation rates, thereby allowing two-dimensional NMR experiments to be carried
      out at very rapid repetition rates (i.e., 5 s-1). (3) The heme proton hyperfine
      resonance pattern for this paramagnetic form of wild-type monomer hemoglobin
      component IV provides an analytical reference for the integrity of the heme
      active site. This is anticipated to facilitate rapid analysis of subsequently
      produced recombinant derivatives of this protein. (4) The cyanide-ligated protein
      has a heme pocket structure similar to those of the O2- and CO-ligated forms of
      the physiologically important, reduced form of the protein, so that the heme and
      proximal histidine proton assignments will serve as a basis for further
      assignments within the heme binding site. Complete assignments, in combination
      with recombinant derivatives of this monomer hemoglobin, will give further
      insight into local interactions that influence ligand binding kinetics and heme
      orientational isomerism.

PMID- 8142406
TI  - Characterization of the active site of p21 ras by electron spin-echo envelope
      modulation spectroscopy with selective labeling: comparisons between GDP and GTP
      forms.
AB  - Selectively labeled samples of human H- or N-ras p21 ligated to MnIIGDP or
      MnIIGMPPNP were studied by electron spin-echo envelope modulation spectroscopy in
      order to define the protein environment around the divalent metal. We
      incorporated [4-13C]-labeled Asx into p21.MnIIGDP and found that the distance
      from the carboxyl 13C of Asp57 to MnII is approximately 4.1 A. Our result is
      consistent with indirect coordination of this residue to the metal. From a [2
      2H]Thr-labeled sample, we estimate that the distance from the MnII ion to the 2H
      of Thr35 is at least 5.8 A. Thus, the only protein or nucleotide ligands to the
      metal appear to be Ser17 and the beta-phosphate of GDP, as previously reported
      [Larsen, R. G., Halkides, C. J., Redfield, A. G., & Singel, D. J. (1992b) J. Am.
      Chem. Soc. 114, 9608-9611]. In the 5'-guanylylimido diphosphate (GMPPNP) form of
      p21, Thr35 has been reported by X-ray crystallography to be a ligand of the metal
      via its hydroxyl group, and this residue appears to play a key role in the
      biologically important conformational change upon nucleotide substitution [Pai,
      E. F., Krengel, U., Petsko, G., Goody, R. S., Kabsch, W., & Wittinghofer, A.
      (1990) EMBO J. 9, 2351-2359]. The ESEEM spectrum of p21.MnIIGMPPNP labeled with
      [2-2H]Thr yields a MnII-2H distance of 4.9 A, a distance inconsistent with strong
      coordination. A sample of p21 in which the Thr residues were fully labeled with
      13C and 15N yielded a value of 5.0 A for the distance from MnII to the amide
      nitrogen of Thr35, while the 13C signal is much smaller than expected if Thr35
      were coordinated. A [15N]serine/glycine-labeled sample gives a distance to the
      amide 15N of Ser17 of 3.9 A, consistent with the X-ray structure; a [4-13C]
      labeled Asx sample of p21 gives a distance of approximately 4 A between MnII and
      the label of Asp57, again implying indirect coordination. Both of these values
      are very similar to those found for the GDP form of the protein. The results for
      Thr35, however, reveal a structural difference between the GDP and GTP forms in
      the region of Thr35. In addition, the position of this residue is found to be
      different from the crystal structure and in a manner suggesting that the metal
      ligation of Thr35 does not drive the conformational change that accompanies
      nucleotide substitution.

PMID- 8142407
TI  - Deterministic pressure-induced dissociation of vicilin, the 7S storage globulin
      from pea seeds: effects of pH and cosolvents on oligomer stability.
AB  - A thermodynamic characterization of subunit association of vicilin, a storage
      protein from pea seeds, was performed using a combination of hydrostatic pressure
      and fluorescence spectroscopy. Application of pressure up to 2.4 kbar caused
      dissociation of vicilin subunits, as revealed by (1) size-exclusion PPLC of
      pressurized samples, (2) fluorescence anisotropy measurements of a dansyl-vicilin
      conjugate under pressure, and (3) quenching of the intrinsic fluorescence of
      vicilin. Pressure dissociation data were well described by a model for
      dissociation of a trimer. This enabled calculation of the standard molar volume
      change of association (delta Vo) and the equilibrium dissociation constant at
      atmospheric pressure (Ko); at pH 10 these were found to be delta Vo = 146 mL/mol
      and Ko = 2.2 x 10(-15) M2, respectively, corresponding to C1/2 (the concentration
      of protein at 50% dissociation at atmospheric pressure) = 18 nM and a
      stabilization free energy of -19.6 kcal/mol for the oligomer. Vicilin exhibited
      an anomalously low dependence on protein concentration for pressure dissociation.
      This appeared related to conformational changes in the dissociated subunits,
      which caused a loss of ca. 5 kcal/mol in the free energy of association and to
      structural/energetic heterogeneity in the population of oligomers. Pressure
      dissociation was markedly pH-dependent, with a stabilization free energy loss of
      3.4 kcal/mol upon raising pH from 9 to 10. Circular dichroism and intrinsic
      fluorescence lifetime measurements at atmospheric pressure showed that the
      structure of vicilin was largely unaffected by pH in the range investigated.
      These results suggest that the effect of pH may involve deprotonation of lysine
      residues participating in salt bridges between vicilin subunits. Pressure
      dissociation of vicilin was significantly inhibited by addition of salts (NaCl,
      KCl, LiCl) or glycerol. Dissociation curves obtained in the presence of salts
      enabled calculation of the free energies of stabilization (ranging from ca. -1.2
      to -2.4 kcal/mol) of the vicilin oligomers by these cosolvents. The similar
      effects of salts or glycerol suggest a common mechanism of stabilization of the
      oligomer involving exclusion of the cosolvents from the protein interface and
      preferential hydration of the protein.

PMID- 8142408
TI  - Intracellular early and late modifications of human apolipoprotein A-II. Effect
      of glutamine- +1 to leucine substitution.
AB  - It has been shown previously that apoA-II undergoes several intracellular
      modifications in HepG2 cells (Hussain & Zannis, 1990). In the present study, we
      have generated permanent cell lines in mouse C127 cells which express the normal
      apoA-II gene and a mutated form in which Gln+1 was substituted with Leu (Leu+1).
      This modification was designed to prevent cyclization of the N-terminal glutamine
      of apoA-II and thus identify the isoproteins which are precursors and products of
      the N-terminal cyclization reaction. The C127-expression cells were also utilized
      to study the cellular compartments where the apoA-II modifications occur as well
      as the importance of the modifications for apoA-II trafficking and secretion. We
      have found that apoA-II (Gln+1) synthesized by C127 and HepG2 cells had similar
      isoproteins. In both cell types, unmodified pro-apoA-II, designated isoprotein 3,
      had a similar isoelectric point as the cell-free translation product of apoA-II
      mRNA, suggesting that isoprotein 3 results from cleavage of the signal peptide.
      Isoprotein 3 represents an unmodified apoA-II isoprotein and undergoes an early
      modification into a more acidic isoprotein 1, which differs from isoprotein 3 by
      two negative charges. Brefeldin A treatment of the cells did not prevent the
      formation of isoprotein 1, suggesting that this modification occurs in a pre
      Golgi compartment. Neuraminidase treatment of secreted apoA-II isoproteins did
      not affect isoprotein 1, indicating that it is not sialylated isoprotein.
      Isoprotein 1 undergoes further modifications which are consistent with cleavage
      of the propeptide, N-terminal cyclization and sialylation most likely resulting
      from O-glycosylation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142409
TI  - A role for cholesterol as a structural effector of the nicotinic acetylcholine
      receptor.
AB  - The effects of cholesterol on the protein structure and on the ionic channel
      activity of purified acetylcholine receptor (AcChR) reconstituted into lipid
      vesicles have been studied, respectively, by Fourier-transform infrared
      spectroscopy and by rapid kinetics of cation influx. Reconstitution of the AcChR
      in asolectin phospholipid vesicles in the absence of either cholesterol or the
      nonpolar lipids present in crude asolectin extracts results in a considerable
      loss of the ability of the AcChR to support cation channel function. This
      functional loss is accompanied by spectral changes in the conformationally
      sensitive amide I band of the protein infrared spectrum which are indicative of
      alteration in the protein secondary structure. Quantitative estimation of such
      alteration by band-fitting analysis reveals a marked decrease in ordered protein
      structures such as the alpha-helix and beta-pleated sheet, concomitant with an
      increase in less ordered structures appearing at 1644 cm-1 in the infrared
      spectrum. Furthermore, the addition of increasing amounts of cholesterol to the
      reconstituted bilayer produces a progressive, complete recovery both in the
      control of cation channel function and in the infrared spectrum. This restoration
      of AcChR structure and function by cholesterol, however, does not occur when the
      AcChR is reconstituted in vesicles made from purified egg phosphatidylcholine,
      thus suggesting that the presence in the reconstituted bilayer of phospholipids
      other than phosphatidylcholine may be required for cholesterol to exert its
      modulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142410
TI  - Adaptation to altered growth temperatures in Acholeplasma laidlawii B: Fourier
      transform infrared studies of acyl chain conformational order in live cells.
AB  - Acholeplasma laidlawii B cells, highly enriched in saturated C14 and C15 fatty
      acids, have been grown at several temperatures. Conformational order in the acyl
      chains of live cell membranes has been monitored with Fourier-transform infrared
      (FT-IR) spectroscopy. Coupled CH2 wagging progressions, characteristic of the all
      trans conformation, have been used to quantitatively monitor the extent of trans
      gauche isomerization. A simple model relating the changes in the progression
      intensity to the introduction of gauche rotamers into the acyl chains suggest
      that at the growth temperature (25 or 37 degrees C for the C14-enriched cells, 30
      or 37 degrees C for the C15-enriched cells) the cell membrane contains about 1.5
      gauche bonds per acyl chain. The thermotropic response of the CH2 stretching
      frequencies near 2850 cm-1 reveals that the gel-liquid-crystal phase transition
      is shifted toward lower temperatures when the growth temperature is reduced. In
      addition, at any given temperature, the cells grown at lower temperature are more
      conformationally disordered than their counterparts grown at higher temperature.
      This behavior is consistent with the quantitative results from the CH2 wagging
      measurements. The data reveal that A. laidlawii B cells can control the overall
      conformational state of their membranes and that the observed degree of disorder
      (1.5 +/- 0.3 gauche bonds/acyl chain), when achievable, provides optimum cell
      viability. The ability of this microorganism to control the degree of membrane
      disorder delineates one possible pathway for homeoviscous adaptation.

PMID- 8142411
TI  - O2-dependent cleavage of DNA by tetrazomine.
AB  - A mechanism for the reduction of molecular oxygen that results in the O2
      dependent cleavage of both single-stranded and double-stranded DNA by the
      antitumor antibiotic tetrazomine (1) is presented. The results are discussed in
      the context of a redox self-disproportionation of the oxazolidine moiety of
      tetrazomine. Comparisons are made to the structurally analogous natural product
      quinocarcin (2) in which, like tetrazomine, the oxazolidine moiety is invoked in
      redox chemistry, which ultimately results in the reduction of molecular oxygen to
      superoxide.

PMID- 8142412
TI  - The cDNA sequence of the flavoprotein subunit of human heart succinate
      dehydrogenase.
AB  - We report the full-length cDNA sequence for the flavoprotein subunit of human
      heart succinate dehydrogenase (succinate: (acceptor) oxidoreductase EC 1.3.99.1).
      Identical sequence was obtained for part of the cDNA of the human placental
      flavoprotein, in contrast to a previously published sequence. The human sequence,
      like the bovine one, contains a cysteine triplet and at the active site there is
      an additional cysteine when compared with yeast or prokaryotes.

PMID- 8142413
TI  - ESEEM and ENDOR studies of the Rieske iron-sulphur protein in bovine heart
      mitochondrial membranes.
AB  - Electron nuclear double resonance (ENDOR) and electron spin echo envelope
      modulation (ESEEM) were applied to the respiratory-chain iron-sulphur clusters in
      natural bovine heart mitochondrial membranes. By using specific reduction,
      signals were observed from the Complex III Rieske [2Fe-2S] cluster. In ENDOR, 1H
      hyperfine couplings in the range 0.5-7 MHz were observed. In ESEEM, modulations
      were obtained which were assigned to two 14N nuclei of directly-coupled imidazole
      ligands. The ESEEM spectra are similar to previous observations on purified iron
      sulphur proteins of this type, in which the iron-sulphur cluster is coordinated
      by two cysteine and two histidine ligands. They confirm that the coordination of
      the cluster in the purified proteins, with two cysteinyl sulphur and two
      histidine nitrogens, is unchanged from its natural mitochondrial membrane
      environment. In order to investigate the possible interaction of the membrane
      bound Rieske protein with quinones, measurements were conducted on membranes
      preincubated with 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT), and in
      the pH range 6-7.5. No significant changes were detected, either in the proton
      hyperfine couplings as detected by ENDOR, or in the nitrogen couplings to the
      histidines as detected by ESEEM.

PMID- 8142414
TI  - ESEEM studies of the iron-sulphur clusters of succinate dehydrogenase in Arum
      maculatum spadix mitochondrial membranes.
AB  - We have performed ESEEM spectroscopy in order to obtain structural information
      about the environment of the [2Fe-2S] cluster and the [3Fe-4S] cluster of
      succinate dehydrogenase (Centres 1 and 3, respectively) in intact Arum maculatum
      mitochondrial membranes. Both iron-sulphur clusters showed modulations indicative
      of 14N in the three-pulse echo decay envelopes. We have estimated the hyperfine
      couplings for the reduced [2Fe-2S] cluster (A approximately 1.1 MHz) and the
      oxidised [3Fe-4S] cluster (A approximately 0.8 MHz). Our results are compared
      with ESEEM data obtained for purified [2Fe-2S] cluster-containing proteins,
      namely Spirulina platensis ferredoxin, a protein for which the three-dimensional
      structure is known, and Escherichia coli fumarate reductase. The hyperfine and
      quadrupolar coupling parameters determined are consistent with a weak interaction
      of Centre 1 and Centre 3 with peptide 14N, rather than 14N of imidazole rings.

PMID- 8142415
TI  - Product-activation of Escherichia coli membrane-bound H(+)-ATPase (F1F0-ATPase)
      connected with epsilon-subunit at alkaline pH.
AB  - Mutant strain AN1518 or AN2387 (Gly48-->Asp in epsilon-subunit) and partial
      revertant strain AN2540 (Gly48-->Asp, Pro47-->Ser in epsilon-subunit) of E. coli
      were used in a kinetic study of membrane-bound H(+)-ATPase. It was found that at
      pH 9.0 mutant strain AN1518 or AN2387 and partial revertant strain AN2540 gave a
      low initial rate, which increased with time until linearity was reached after 1-2
      min. This phenomenon was prominent in mutant strains, but was not so obvious in
      wild-type AN346 of E. coli; this property is similar to F1-ATPase reported by Cox
      [1]. The mechanism of the slow activation of membrane-bound H(+)-ATPase was
      further investigated in this paper. The experimental results indicated that the
      hydrolytic rate of E. coli F1F0-ATPase that increased with time was membrane
      protein concentration- and pH-dependent, and that the product ADP produced during
      ATP hydrolysis is the factor causing the slow activation. Preincubation of the
      hydrolytic product ADP with a concentration comparable to that produced in the
      assay (20 microM) caused initial activation of ATP hydrolysis and abolished the
      slow activation. On the other hand, with the removal of ADP during the progress
      of the hydrolytic reaction it could be seen that the slow activation was
      abolished as well. In order to test the relationship between the epsilon-subunit
      and ADP involved in the slow activation, trypsin treatment was carried out on the
      membrane-bound H(+)-ATPase of various strains. The activation observed after
      trypsin treatment was on the order of AN1518 > AN2540 > AN346. The activation
      effects of ADP and trypsin were not found to be additive. This implies that ADP
      acted in a similar way to trypsin, i.e., to cause removal of the epsilon-subunit.
      A tentative mechanism of the slow activation was proposed that ADP, a product of
      ATP hydrolysis, could induce conformational changes of F1F0 at alkaline pH 9.0,
      thus weakening the binding strength between the epsilon-subunit and other
      subunits of F1F0, and resulting in removal or partial removal of the epsilon
      subunit. This further impaired the coupling of F1 and F0 in the mutant strains;
      as a consequence the rate of ATP hydrolysis was increased.

PMID- 8142416
TI  - Ultrastructural localisation of carnitine acetyltransferase activity in
      mitochondria of rat myocardium.
AB  - The acetyl CoA/CoA ratio is an important regulating factor of beta-oxidation in
      mitochondria and hence of energy production in the myocardium. Carnitine
      acetyltransferase provides one of the control mechanisms for this ratio during
      changing energy demand in the heart muscle, possibly by buffering the CoA and
      carnitine concentration for sustained beta-oxidation. In search for a possible
      correlation between the activity of this enzyme and ultrastructural changes in
      heart mitochondria, carnitine acetyltransferase was cytochemically localised in
      rat myocardium, brought into different metabolic states. In this work we confirm
      previous observations, namely the formation of contact sites between inner and
      outer mitochondrial membranes upon catecholaminergic stimulation of the
      myocardium. It is further shown that this contact site formation might be a
      prerequisite for carnitine acetyltransferase to demonstrate enzymatic activity
      and hence control of beta-oxidation in myocardial mitochondria.

PMID- 8142417
TI  - Modulation of GTP-dependent fusion by linoleic and arachidonic acid in
      derivatives of rough endoplasmic reticulum from rat liver.
AB  - The effect of modulation of the content of unsaturated free fatty acids on GTP
      dependent fusion of stripped rough microsomes from rat liver was determined.
      Cytidine monophosphate, CDP and CTP were all observed to be able to stimulate
      free fatty acid accumulation and coincident membrane fusion. GTP was required for
      membrane fusion in the presence of cytidine nucleotide but was not required for
      free fatty acid accumulation. In the presence of GTP and cytidine nucleotide, the
      addition of ATP and CoA led to the synthesis of triacyglycerol and marked
      inhibition of both free fatty acid accumulation and membrane fusion. Delipidated
      bovine serum albumin also inhibited both free fatty acid accumulation and
      membrane fusion. Analysis by gas chromatography indicated that linoleic acid and
      arachidonic acid were the most actively fluctuating of the accumulated free fatty
      acids. Comparison by quantitation indicated a high correlation between GTP
      dependent membrane fusion and changes in amount of unesterified linoleic acid and
      arachidonic acid. The results suggest that polyunsaturated free fatty acids may
      be required for GTP-dependent membrane fusion.

PMID- 8142418
TI  - Purification of the rat-liver mitochondrial dicarboxylate carrier by affinity
      chromatography on immobilized malate dehydrogenase.
AB  - The dicarboxylate carrier of rat-liver mitochondria, extracted by Triton X-100
      and partially purified by hydroxylapatite chromatography, was retained by malate
      dehydrogenase immobilized on Sepharose gel, and eluted with 0.4 M NaCl. SDS
      polyacrylamide gel electrophoresis of the eluate showed a predominant peptide
      band with an M(r) of 28,000. The purified protein, incorporated into liposomes,
      mediated a butylmalonate sensitive malonate(out)/malate(in) exchange that was
      inhibited by p-chloromercuriphenylsulfonate. Sulfate, malate and phosphate
      decreased the rate of exchange. The highly purified protein displayed all the
      properties of the dicarboxylate carrier. Moreover, the results suggest a possible
      functional interaction between mitochondrial carrier protein and malate
      dehydrogenase.

PMID- 8142419
TI  - Correlation between inhibition of cytoskeleton proteolysis and anti-vesiculation
      effect of calpeptin during A23187-induced activation of human platelets: are
      vesicles shed by filopod fragmentation?
AB  - Platelets were incubated in the presence of calpeptin to inhibit calpain-mediated
      cytoskeleton proteolysis during further activation by Ca2+ ionophore A23187. The
      appearance of filamin and myosin subfragments (93 kDa and 135 kDa, respectively)
      was inhibited by low calpeptin doses (1 microgram/ml). Higher doses (10-20
      micrograms/ml) were required to completely inhibit talin and filamin degradation.
      Vesiculation strongly depended on cytoskeleton proteolysis and was reduced by 60%
      when platelets were preincubated with 10 micrograms/ml calpeptin. Activated
      platelets bore longer and more filopods when pretreated with calpeptin. Filopods
      were straight and regular when high calpeptin doses were used, whereas they were
      shorter and broader with bloated surfaces when calpeptin was omitted. Some
      bloated areas were also found in straight filopods. These results suggest that
      the cytoskeleton proteolysis, and more specifically filamin proteolysis, induced
      bloating of filopod surfaces, thus facilitating fragmentation of filopod into
      vesicles.

PMID- 8142420
TI  - Transport properties of Asp-51-->Glu and Asp-120-->Glu mutants of the melibiose
      carrier of Escherichia coli.
AB  - Asp-51-->Glu and Asp-120-->Glu mutants of the melibiose carrier of Escherichia
      coli were investigated for their cation/sugar cotransport properties. The carrier
      containing Glu-51 showed proton/melibiose cotransport but was extremely defective
      in Na+ or Li+ stimulation of sugar accumulation. On the other hand, the carrier
      containing Glu-120 had lost the ability to couple protons with melibiose uptake
      while retaining considerable Na+ or Li+ cotransport with melibiose (40-fold
      accumulation versus 90-fold for the wild type in the presence of Na+). It is
      concluded that both Asp-51 and Asp-120 are important for cation recognition.

PMID- 8142421
TI  - Influence of the lipid matrix on incorporation and function of LPS-free porin
      from Paracoccus denitrificans.
AB  - We have studied the role of lipopolysaccharide (LPS) for the insertion of LPS
      free porin from Paracoccus denitrificans into planar lipid bilayers and its
      function therein. For this, we reconstituted the porin into different asymmetric
      planar lipid bilayers with or without LPS and into symmetric phospholipid
      bilayers. LPS-free porin added to the various bilayer systems was found to induce
      a step-wise increase in membrane conductance with different incorporation rates,
      depending on the presence of LPS in the bilayer leaflet opposite to porin
      addition. The incorporation rate into asymmetric LPS/phospholipid membranes from
      the phospholipid side was more than 10-fold higher than that observed for pure
      phospholipid membranes. The porin formed general diffusion pores without any salt
      specificity. The mean single-channel conductance did not depend on the presence
      of LPS and was about 4.2 nS for a subphase containing 1 M KCl in all systems
      tested. At certain applied transmembrane voltages, which depended on membrane
      composition and were approximately greater than 100 mV for the LPS/phospholipid
      system, single-channel closing in three steps was observed. Differences in the
      voltage dependence of porin-channel closing could be correlated with the surface
      charge of the bilayer. From the voltage-dependent gating behaviour proof for an
      oriented incorporation of the porin molecules, depending on the side of porin
      addition, and evidence for their orientation could be derived. Measurements at
      temperatures above and below the beta<==>alpha phase transition temperature of
      LPS gave evidence for the influence of membrane rigidity on the gating behaviour.

PMID- 8142422
TI  - Phosphatidylserine headgroup diastereomers translocate equivalently across human
      erythrocyte membranes.
AB  - The natural chiral phospholipid substrates for the plasma membrane
      aminophospholipid translocator are L-alpha-phosphatidyl-L-serine and L-alpha
      phosphatidylethanolamine. The glyceric D-stereoisomers of these lipids, D-alpha
      phosphatidyl-L-serine and D-alpha-phosphatidylethanolamine, are not translocated
      (Martin, O.C. and Pagano, R.E. (1987) J. Biol. Chem. 262, 5890-5898). We have
      synthesized a diastereomer of phosphatidylserine, L-alpha-phosphatidyl-D-serine,
      to study the effects of headgroup stereochemistry on translocation. The
      diastereomer was synthesized as the dilauroyl (12:0) species, and the
      translocation was monitored by human erythrocyte morphology changes at 25 degrees
      C and 37 degrees C. Unlike other phosphatidylserine stereoisomers, L-alpha
      phosphatidyl-D-serine is translocated to the same degree as the natural L,L
      isomer. Incorporation of apparently equal amounts of the L,D- and L,L
      diastereomers does produce minor quantitative differences in the cell
      morphological response, possibly as a result of differences in lipid packing of
      the two isomers.

PMID- 8142423
TI  - Activation of osmotically-activated potassium transporters after injection of
      mRNA from A6 cells in Xenopus oocytes.
AB  - The different potassium pathways, under iso-osmotic or hypo-osmotic conditions,
      were examined in Xenopus oocytes that were micro-injected with mRNA from A6
      cells. Hypo-osmotically stimulated 86Rb (K+) effluxes could be measured from
      intact oocytes 1-4 days after injection of 25 ng of poly (A)+ RNA isolated from
      A6 cells. 86Rb (K+) effluxes were 2.2 times higher from oocytes micro-injected
      with 25 ng of poly(A)+ RNA, than from water injected control oocytes. Water
      injected oocytes themselves, however, were 7-fold more responsive to a hypo
      osmotic shock than non-injected Xenopus oocytes. There was no significant effect
      of the different K+ transport blockers tested (TEA, bumetanide, glybenclamide or
      quinidine) on the endogenous 86Rb (K+) effluxes from non-injected oocytes in
      either iso- or hypo-osmotic media. The 86Rb (K+) effluxes from water-and mRNA
      injected oocytes in hypo-osmotic media were both inhibited by TEA. In mRNA
      injected oocytes the increase in 86Rb (K+) transport following a medium dilution
      was also inhibited in the presence of glybenclamide or bumetanide. The present
      study reports that the activation of hypo-osmotically-activated potassium
      transporters in the oocytes of Xenopus laevis. after injection of mRNA from A6
      cells differs quantitatively and in part qualitatively (glybenclamide
      sensitivity) from the endogenous K+ pathways of non-injected and of water
      injected Xenopus oocytes.

PMID- 8142424
TI  - Internal Ca2+ ions inactivate and modify ATP-sensitive potassium channels in
      adult mouse skeletal muscle.
AB  - The effects of internal Ca2+ ions on single ATP-sensitive potassium channels
      (KATP channels) were studied in inside-out membrane patches excised from mouse
      skeletal muscle. Channel activity was high when patches were excised in a Ca(2+)
      free, Na(+)-rich solution and declined irreversibly within seconds in the
      presence of internal Ca2+ (0.1 and 2 mM). After Ca(2+)-dependent inactivation of
      the channels, the ATP concentration-response curve was steeper and 50% channel
      blockage occurred at a lower ATP concentration than before inactivation. ATP (50
      microM) in a K(+)-rich solution bathing the intracellular membrane surface
      reduced the open-probability of KATP channels to 18% before and to 10% after
      exposure of the patch to internal Ca2+ (0.1 mM). The block of KATP channels by
      ATP (50 microM) was also enhanced by internal Ca2+ at a concentration of 13
      microM. It is concluded that internal Ca2+ ions can both inactivate KATP channels
      and modify the active channels. KATP channels modified by Ca2+ are blocked more
      strongly by ATP than unmodified channels.

PMID- 8142425
TI  - Diacylglycerol, phosphatidylserine and Ca2+: a phase behavior study.
AB  - The interaction of 1,2-dipalmitoylglycerol (1,2-DPG) with
      dipalmitoylphosphatidylserine (DPPS) has been studied in the presence and in the
      absence of Ca2+ by using differential scanning calorimetry (DSC) and 31P-nuclear
      magnetic resonance (31P-NMR). In the absence of Ca2+, DSC showed that 1,2-DPG
      increased the phase transition of DPPS, effect already noticed at very low 1,2
      DPG concentrations, whereas lipid immiscibilities were detected at concentrations
      of 1,2-DPG higher than about 30 mol%. 31P-NMR indicated that lamellar phases were
      always present at concentration of 1,2-DPG lower than about 35 mol%, but at
      higher concentrations non-lamellar phases may be present in the fluid phase. As
      observed by DSC, the apparent pKa of the carboxyl group of DPPS was increased
      slightly in the presence of 1,2-DPG. In the presence of Ca2+, the effect of 1,2
      DPG was to further increase the temperature of the onset of the phase transition,
      indicating an stabilization of the most rigid phase in the DPPS/1,2-DPG/Ca2+
      samples. Even concentrations of 1,2-DPG as low as 1 mol% of the total lipid
      already produced a noticeable effect. Moreover, lipid immiscibilities were
      apparent at concentrations of 1,2-DPG higher than 20 mol%. Furthermore, the
      transition of the DPPS/Ca2+ complex observed by DSC at 155 degrees C was
      perturbed by the presence of 1,2-DPG, indicating a change in the structure of the
      crystalline complex. Interestingly, the effect of non-saturating Ca2+
      concentrations on the DPPS phase transition was enhanced by the presence of 1,2
      DPG. The effect reported here may be significant for a number of situations where
      Ca2+, phosphatidylserine and diacylglycerols are involved, such as fusion of
      membranes, where diacylglycerol may facilitate Ca(2+)-induced fusion, or the
      activation of enzymes such as protein kinase C and phospholipases.

PMID- 8142426
TI  - Mutational analysis of the COOH-terminal hydrophobic domain of bovine liver 5'
      nucleotidase as a signal for glycosylphosphatidylinositol (GPI) anchor
      attachment.
AB  - In order to address the minimum domain of the COOH-terminal hydrophobic region
      responsible for GPI modification of bovine liver 5'-nucleotidase, we constructed
      a series of the deletion mutants of the COOH-terminus and expressed them in COS
      cells. Cells transfected by the deletion mutant of 6 amino acids (-IIILYQ) from
      the hydrophobic domain (-FSLIFLSVLAVIII-LYQ) did not show any elevation of cell
      surface-associated 5'-nucleotidase activity, whereas the 2 (-YQ) or 4 (-ILYQ)
      amino acid deletion mutant retained the bovine liver-derived activity on the cell
      surface as a GPI-anchored protein. Loss of half the hydrophobic domain (6 or 8
      amino acids) resulted in accumulation of the activity in the cell. On the other
      hand, deletion of the whole hydrophobic domain (17 amino acids) or the entire
      cleaved-off domain (25 amino acids) made the product secreted into the medium. In
      conclusion, the hydrophobicity of 13 amino acids in length was enough for the GPI
      modification of the bovine liver 5'-nucleotidase.

PMID- 8142427
TI  - A comparative study on the uptake of alpha-aminoisobutyric acid by normal and
      immortalized human embryonic kidney cells from proximal tubule.
AB  - We investigated whether an immortalized human kidney epithelial cell line (IHKE),
      compared with normal embryonic cells (NHKE), can be used as a representative
      system with which to characterize the transport of neutral amino acids in the
      proximal tubule of the human kidney. The IHKE cell line, immortalized by
      treatment with NiSO4, exhibited microvilli and enzyme markers specific for highly
      specialized tubule cells. The Na(+)-dependent uptake of alpha-aminoisobutyric
      acid (AIB) by IHKE and NHKE cells occurred by means of a single transport system
      with identical half-saturation constants, but the capacity for uptake was higher
      in the immortalized cells. Proton-dependent influx of AIB was also mediated by a
      single transport component with similar uptake characteristics in both types of
      cells. Imposition of an H(+)-gradient to a Na(+)-gradient reduced the sodium
      dependent uptake of AIB with the exception of short incubation time (1 min),
      where addition of a proton gradient produced a marked increase in the Na(+)
      dependent influx of AIB in NHKE but not in IHKE cells. Competition experiments
      revealed that the Na(+)-dependent uptake at 50 microM AIB was reduced by neutral
      alpha-amino acids in the two cell lines. L-Glutamate, L-aspartate, L-arginine and
      the beta-amino acid taurine had no effect. Only in the IHKE cell line did
      addition of 5 mM L-lysine produce a slight inhibition. Except for L-proline all
      of the neutral and acidic amino acids tested reduced the H(+)-dependent uptake of
      AIB in the IHKE cell line. By contrast, addition of L-aspartate did not influence
      the transport of AIB in NHKE cells. L-Arginine, but not L-lysine decreased the
      influx in both cell lines. We conclude that the IHKE cell line has retained the
      capability to accumulate AIB by transport protein(s) similar to those present for
      neutral alpha-amino acids in NHKE cells.

PMID- 8142428
TI  - Immunodetection and characterization of proteins implicated in renal
      sodium/phosphate cotransport.
AB  - Polyclonal antibodies raised against the 14-amino acid C-terminal portion of the
      rabbit renal brush-border membrane Na+/Pi cotransporter, as deduced from the
      nucleotide sequence of the cloned NaPi-1 gene, were used for Western blot
      analysis of renal brush-border membrane proteins from rat, rabbit and beef.
      Proteins of 65 kDa from the rat, 64 kDa from the rabbit, and 38, 66, 77, 92, 110,
      176 and 222 kDa from the beef were specifically labelled. The affinity of the
      antibodies was much greater, however, for the proteins of the rat and rabbit than
      for those of the beef. The rat 65-kDa antigen was readily detected in brush
      border membranes isolated from kidney cortex, but was absent from the basolateral
      membrane and the cytosolic and microsomal fractions of this tissue, in agreement
      with the subcellular localization of the Na+/Pi cotransporter. This antigen was
      however several-fold more abundant in the juxtamedullary portion of the cortex
      than in the outer portion. Despite a strong stimulation in phosphate transport, a
      low-phosphate diet had little influence on the amount of antigen detected. An
      additional peptide-displaceable band corresponding to a protein of 250 kDa
      appeared when beta-mercaptoethanol was omitted during electrophoresis, in
      agreement with the possibility that disulfide bonds may be involved in the
      regulation of renal phosphate transport activity.

PMID- 8142429
TI  - Binding of naturally occurring antibodies to oxidatively and nonoxidatively
      modified erythrocyte band 3.
AB  - Both oxidative clustering (elicited by diamide treatment) and nonoxidative
      clustering (elicited by zinc/BS3 (bis[sulfosuccinimidyl]suberate) treatment) of
      erythrocyte integral membrane proteins induce binding of autologous antibodies
      with anti-band 3 specificity, followed by complement deposition and phagocytosis.
      Autologous antibodies eluted from nonoxidatively clustered erythrocytes bind to
      and stimulate phagocytosis of oxidatively damaged erythrocytes. Those eluted
      antibodies bind specifically to disulfide-crosslinked band 3 dimers generated by
      diamide treatment. Band 3 dimerization and antibody binding are abrogated by
      cleavage of band 3 cytoplasmic domain. Thus, disulfide-crosslinked band 3 dimers
      are the minimal band 3 aggregate with enhanced affinity for anti-band 3
      antibodies. The eluted antibodies do not bind to band 3 dimers generated
      nonoxidatively by BS3 treatment but bind avidly to larger band 3 clusters
      generated nonoxidatively by zinc/BS3 treatment. Possibly, disulfide crosslinking
      of cytoplasmic domain cysteines induces reorientation of intramembrane domains as
      to expose putative anti-band 3 epitopes and allow bivalent binding of anti-band 3
      antibodies. Extensive nonoxidative band 3 clustering appears to disrupt the
      native band 3 conformation and generate reoriented dimers which expose putative
      anti-band 3 epitopes in the proper distance and orientation as to allow bivalent
      antibody binding.

PMID- 8142430
TI  - Effect of mitochondrial protein concentration on the efficiency of outer membrane
      removal by the cholesterol-selective detergent digitonin.
AB  - The effects of different mitochondrial protein concentrations on the efficiency
      of digitonin titration of the outer mitochondrial membrane were investigated in
      isolated rat liver mitochondria. Isolated mitochondria were subjected to
      treatment with digitonin concentrations ranging from 0 to 0.40 mg digitonin per
      mg protein. This digitonin concentration range was used in incubations containing
      5 to 50 mg mitochondrial protein per ml. Significant differences in the
      efficiency of outer membrane removal by digitonin titration were noted at protein
      concentrations of less than 20 mg per ml. Estimation of the effective
      concentration of digitonin required to remove 50% of the outer membrane indicated
      that in general, as the protein concentration decreases, the amount of digitonin
      required to remove the outer membrane increases. Significant differences were
      also noted in the amount of digitonin needed for removal of 95% of the outer
      membrane between 5, 10 and 20 mg/ml with the effect of protein concentration
      disappearing above 20 mg/ml. No effect of protein concentration was found on the
      disruption of the inner membrane by digitonin as judged by leakage of matrix
      marker enzyme activity and by release of inner membrane marker enzyme activity.
      The conclusions of these studies indicate that at relatively low mitochondrial
      protein concentrations (< 20 mg/ml), the efficiency of digitonin in removing the
      outer membrane is substantially reduced.

PMID- 8142431
TI  - Oleic acid inhibition of Na+/D-glucose transport in isolated renal brush-border
      membranes: role of lipid physical parameters and trans Na(+)-inhibition.
AB  - Inhibition of Na+/D-glucose transport by oleic acid was investigated in renal
      brush-border membrane vesicles (BBMV). Lipid physical parameters were determined
      by spectrofluorometry. cis-Unsaturated C16-C22 long-chain fatty acids (LCFA) as
      oleic acid reduced nonzero limiting anisotropy r infinity with DPH and 12-AS as
      probes and decreased rotational correlation time phi of 12-AS. At 8 s and 15 s
      Na+/D-glucose transport was competitively inhibited. A positive correlation
      existed between decrease in r infinity (acyl chain order) or decrease in
      rotational correlation time phi (= increase in 'fluidity') and inhibition of
      Na+/D-glucose transport. Except elaidic acid trans unsaturated and saturated LCFA
      had no effect on fluorescence anisotropy and Na+/D-glucose transport. Per cent
      transport inhibition was unaffected by 0 voltage clamping and by FCCP. Ki for
      trans Na(+)-inhibition of D-glucose transport was 29 mmol/l. Na(+)-transport was
      stimulated by oleic acid, exceeding the Ki value for trans Na+ inhibition.
      CONCLUSION: oleic acid inhibits Na+/D-glucose transport by a decrease in lipid
      acyl chain order and an increase in 'fluidity', by trans Na(+)-inhibition and
      presumably by a third unknown mechanism.

PMID- 8142432
TI  - Charge- and pH-dependent binding sites for dibucaine in ionic micelles: a
      fluorescence study.
AB  - Binding of micromolar concentrations of the local anesthetic dibucaine to
      micelles of cationic, zwitterionic and anionic detergents was studied using the
      fluorescence emission of dibucaine. Difference in quantum yields for charged and
      neutral dibucaine allowed to obtain shifts of pKa values due to binding.
      Estimates for the electrostatic potential affecting the tertiary amine of
      dibucaine were obtained from the pKa shifts. Change of fluorescence emission upon
      binding allowed to obtain the binding constants of both charged and neutral
      dibucaine to the micelles. The binding constant for the neutral form is
      essentially independent of micelle charge and of specific differences in
      detergent structure. Consistency between the ratio of neutral to cationic
      dibucaine binding constants and the measured pKa shift was tested. For LPC
      micelles complete agreement was found. For CTAC, however, the ratio of binding
      constants does not explain the pKa shift. The discrepancy between the results is
      used to estimate the errors involved upon neglecting non-coulombic electrostatic
      interactions of drugs to charged membrane surfaces. Fluorescence quenching with
      sodium iodide and nitroxide stearic acid derivatives allowed a depth profiling of
      the drug in the micelles.

PMID- 8142433
TI  - Regulation of calmodulin binding to the ATP extractable 110 kDa protein (myosin
      I) from chicken duodenal brush border by 1,25-(OH)2D3.
AB  - In earlier studies we observed that the active vitamin D metabolite 1,25-(OH)2D3
      increased the calmodulin content of purified duodenal brush-border membrane
      vesicles where it bound principally to the 110 kDa protein myosin I. In this
      study we further evaluated the regulation of calmodulin binding to ATP releasable
      myosin I. Whole brush borders (BB) or purified brush-border membrane vesicles
      (BBMV) were prepared from duodena of vitamin D-deficient rachitic chicks treated
      12-18 h before killing with either 625 pmol 1,25-(OH)2D3 or vehicle. The ATP
      extractable myosin I from BB resulted in an 1.6-fold increase of calmodulin
      binding to the 110 kDa band after treatment with 1,25-(OH)2D3. In contrast to BB,
      ATP extraction of myosin I from purified BBMV required alamethicin for ATP entry.
      As for BB extracts, calmodulin binding to the 110 kDa band in BBMV extracts was
      also increased about 2.4-fold by 1,25-(OH)2D3. It was concluded that both intact
      BB and purified BBMV showed the same type of increase in calmodulin binding to
      ATP releasable myosin I by 1,25-(OH)2D3. To see whether 1,25-(OH)2D3 increased
      the intrinsic affinity of calmodulin binding to myosin I, the ATP extractable
      myosin I from BB was purified from rachitic chicks treated with 1,25-(OH)2D3 or
      vehicle. In contrast to ATP extracts of BB or BBMV, calmodulin binding to the
      purified myosin I was not different between preparations from 1,25-(OH)2D3- or
      vehicle-treated chicks. We conclude that 1,25-(OH)2D3 does not change the
      affinity of calmodulin binding to myosin I but increases the amount of myosin I
      in the membrane or alters its ATP releasability. It was further investigated
      whether phosphorylation is involved in these 1,25-(OH)2D3 dependent
      posttranslational changes of myosin I. Phosphorylation of brush-border membrane
      proteins in vivo was performed by incubation of [32P]P(i) in the lumen of a
      ligated duodenal loop in situ for 15 min. Brush-border membrane proteins were
      phosphorylated in vitro by incubating BB or BBMV with [gamma-32P]ATP for 1 min.
      Incubation experiments in vivo and in vitro in fact resulted in phosphorylation
      of several proteins including 110 kDa proteins. However, there was no specific
      effect of 1,25-(OH)2D3 on phosphorylation of 110 kDa proteins. We conclude that
      the effects of 1,25-(OH)2D3 on protein phosphorylation are minimal and not likely
      to explain 1,25-(OH)2D3 stimulated calmodulin binding to ATP extractable brush
      border membrane myosin I and 1,25-(OH)2D3 stimulated changes of calcium uptake
      across the brush-border membrane.

PMID- 8142434
TI  - Induction of secondary structure in the peptide hormone motilin by interaction
      with phospholipid vesicles.
AB  - Motilin is an intestinal peptide hormone that binds to a membrane bound receptor
      located in the gut tissue. Circular dichroism (CD) was used to study the
      interaction between either porcine or rabbit motilin or a 1-16 fragment of
      porcine motilin, with model systems of lipid membranes: sodium dodecyl sulphate
      (SDS), 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG) and 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC). The CD measurements show significant induction
      of secondary structure in both motilins and the fragment when negatively charged
      vesicles (DOPG) or negatively charged micelles (SDS) were present. In contrast,
      neutral DOPC vesicles did not induce any change in the secondary structure
      compared to water, in which a random-like secondary structure dominates. The
      induced secondary structure in the presence of DOPG vesicles is very close to
      that induced by a mixed aqueous solution containing 30% hexafluoroisopropanol, in
      which previous NMR-studies have resulted in a three-dimensional solution
      structure of porcine motilin. In both porcine and rabbit motilin the alpha-helix
      content is about 50%. This is in agreement with the presence of an amphipathic
      helix in the C-terminal half of motilin interacting with phospholipid membranes.
      The interaction appears to be mainly electrostatic in nature, and does not induce
      any significant alterations in the vesicle, as monitored by EPR studies of spin
      labels located at the fifth carbon atom of the backbone in a stearic acid
      molecule. In the 1-16 fragment the alpha-helical content induced by DOPG and SDS
      is only about 20%.

PMID- 8142435
TI  - Accelerated net efflux of 3-O-methylglucose from rat adipocytes: a reevaluation.
AB  - In a study of 3-O-methylglucose transport in insulin-stimulated rat adipocytes
      (catalyzed primarily by the GLUT4 isoform), it was reported that at 37 degrees C
      the Km and Vmax were 2.8-fold higher for net efflux than for equilibrium exchange
      (Vinten, J. (1984) Biochim. Biophys. Acta 772, 244-250). Because of its
      implications for the relative sizes of steps in the transport cycle, we
      reinvestigated this phenomenon. Accelerated net efflux was apparent when the
      extracellular methylglucose was diluted 26-fold but not when it was diluted 11
      fold. When analyzed according to the one-site alternating conformation model, the
      data indicate about a 1.7-fold higher Vmax for efflux than for exchange, only
      about 40% of the difference reported previously. Together with other results in
      the literature, the accelerated net flux indicates that the conformational change
      of the loaded transporter from its outward-facing to its inward-facing form is
      likely the slowest step in the transport cycle, in contrast to the case for
      GLUT1. Experiments at 25 degrees C indicate a lower degree of accelerated net
      flux than at 37 degrees C. This is consistent with the above conformational
      change being the step with the lowest activation energy, as for GLUT1.

PMID- 8142436
TI  - In situ hybridization of mRNA for the gastric H+,K(+)-ATPase in rat oxyntic
      mucosa.
AB  - The H+,K(+)-ATPase member of the phosphorylating ion motive ATPases is composed
      of two subunits, a large alpha-subunit composed of about 1030 amino acids and a
      smaller beta-subunit consisting of about 290 amino acids. By biochemical and
      immunological methods both subunits have been found in high abundance in the
      gastric parietal cell. In the present study in situ hybridization was used for
      localizing and comparing concentrations of the mRNA for the two subunits in the
      gastric epithelium. For this purpose 3H-labelled probes were preferred.
      Hybridization was detected only in the parietal cells. The older parietal cells
      in the bottom of the mucosa gave a weaker hybridization signal than the younger
      parietal cells closer to the surface. The margin of experimental ulcers, where
      the parietal cells are of low differentiation, showed very weak, if any,
      hybridization. The differences observed in hybridization densities may reflect
      differences in mRNA synthesis or stability. It is conceivable that older parietal
      cells, as well as parietal cells of low differentiation, produce relatively small
      amounts of H+,K(+)-ATPase.

PMID- 8142437
TI  - On the validity of lipid dequenching assays for estimating virus fusion kinetics.
AB  - Octadecylrhodamine (R18) has often been used to measure membrane fusion of
      enveloped viruses by fluorescence dequenching. In order to see whether non
      specific R18 exchange between non-fused membranes occurs we have measured fusion
      of influenza virus with erythrocyte membranes by utilizing dequenching of the non
      exchangeable lipid analogue N-(lissamine-rhodamine B
      sulfonyl)diacylphosphatidylethanolamine (N-Rh-PE). Rather low concentration of N
      Rh-PE (< 0.1 mol%) were required to assess fusion since self-quenching in the
      influenza virus membrane was more efficient in comparison to R18. For both
      markers we observed the same kinetics as well as the same extent of fluorescence
      dequenching upon triggering low pH-induced fusion. Non-specific marker transfer
      was not observed. Haemolysis was not affected by either type of fluorophore. Our
      results confirm that R18 is a valuable tool to investigate membrane fusion of
      enveloped viruses in a quantitative manner. Differences in the efficiency of self
      quenching of both markers are discussed.

PMID- 8142438
TI  - Acyl chain length effects related to glycosphingolipid crypticity in phospholipid
      membranes: probed by 2H-NMR.
AB  - Wideline 2H-NMR was used to consider the relationships amongst glycosphingolipid
      and phospholipid fatty acid chain length and glycosphingolipid receptor function,
      in a system classically associated with crypticity. Galactosyl ceramide (GalCer),
      having 18- or 24-carbon fatty acid, was deuterium labelled at the
      conformationally-restricted fatty acid alpha-carbon (C-2). 2H-NMR spectra of N
      [2,2-2H2]stearoyl and N-[2,2-2H2]lignoceroyl GalCer (GalCer with 18-vs. 24-carbon
      selectively deuterated fatty acid) were then compared over a range of
      temperatures in phosphatidylcholine/cholesterol membranes in which the host
      phospholipid had dimyristoyl, dipalmitoyl, or distearoyl fatty acid composition.
      Findings were evaluated in the light of known sensitivity of antibody interaction
      with GalCer to temperature and to both glycolipid fatty acid chain length and
      host matrix fatty acid chain length. Under the conditions of experimentation,
      spectra were not obtainable for glycolipids having rigid body motions that were
      slow on the NMR timescale (10(-4)-10(-5) s)-i.e.. motions typical of non-fluid
      (gel phase) membranes. The systems, DPPC/cholesterol and DSPC/cholesterol, in
      which the original observation was made of increased antibody binding to GalCer
      with long fatty acid, proved to be characterised by receptor motions that were in
      this slow timescale for both 18:0 and 24:0 GalCer at 22-24 degrees C. Under
      conditions for which spectra could be obtained, those for GalCer with [2,2
      2H2]lignoceroyl (24-carbon alpha-deuterated) fatty acid were qualitatively
      similar to those of its 18-carbon analogue in all (fluid) membranes examined.
      However, spectral splittings differed quantitatively between deuterated 18:0 and
      24:0 GalCer at a given temperature, dependent upon host matrix. These differences
      were most marked at lower temperatures and in the longer chain (more ordered)
      matrices, DPPC/cholesterol and DSPC/cholesterol. This suggests that maximum
      effects of glycolipid chain length on glycolipid receptor function may be
      expected to occur in spatially and motionally constrained lipid environments.
      There was little effect of temperature on spectral splittings seen for a given
      sample containing deuterated 18:0 GalCer. The small differences seen could be
      adequately accounted for by relatively minor alterations in glycolipid order and
      backbone conformation. In contrast, 24:0 GalCer in DPPC/cholesterol and
      DSPC/cholesterol displayed significant variation in its spectral splittings as
      the temperature was reduced; and these proved to be the source of the
      quantitative differences between 18:0 and 24:0 GalCer referred to above.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8142439
TI  - Behaviour of complex oligosaccharides at a bilayer membrane surface: probed by 2H
      NMR.
AB  - Deuterium wideline NMR was used in an attempt to directly assess oligosaccharide
      arrangement and motional characteristics of complex glycosphingolipids dispersed
      as minor components in phospholipid membranes. A convenient, general synthetic
      approach was developed which involved replacement of the acetate group of amido
      sugars with deuteroacetate (-COCD3). This provided excellent signal-to-noise when
      applied to the terminal GalNAc residue of globoside, and the terminal NANA
      residue of GM1. Simultaneously, globoside and GM1 fatty acids were replaced with
      stearic acid deuterated at C-2- a probe location sensitive to glycolipid
      hydrophobic backbone orientation and rigid body motion. Deuterated GM1 and
      globoside were studied by 2H-NMR in bilayers of 1-palmitoyl-2-oleoyl
      phosphatidylcholine, in the presence and absence of physiological quantities of
      cholesterol. The monoglycosyl glycosphingolipid, glucosyl ceramide, which is the
      common skeleton of many complex glycosphingolipids including those studied here,
      was also deuterated at fatty acid C-2 for comparative study in the same matrices.
      Correlation with spectra of the complex glycolipids demonstrated that, for a
      given temperature and membrane composition, ceramide backbone conformation was
      very similar amongst the species studied. Spectral features of GM1 deuterated on
      terminal NANA and assembled at a membrane surface, were found to be highly
      consistent with the oligosaccharide conformation determined in studies of GM1 in
      solution. In contrast, globoside deuterated in the terminal GalNAc residue gave
      spectra very different from those predicted on the basis of the conformation
      considered to exist in solution. It seems likely that this result reflects a
      combination of greater oligosaccharide chain flexibility relative to GM1, and the
      presence of the membrane environment. Interestingly, although there was highly
      significant spatial geometry associated with the complex oligosaccharide chains,
      and although temperature and the presence of cholesterol exert measurable effects
      on the membrane-inserted portion, these factors had very little impact on the
      measured spectral parameters associated with the NANA residue of GM1 or the
      terminal GalNAc residue of globoside. This seems to indicate lack of sensitivity
      of the complex oligosaccharide chains to conformation and internal motions of the
      hydrophobic chain segments in these fluid and semi-fluid membranes; and has
      important implications for mechanisms of crypticity.

PMID- 8142440
TI  - The structural differences between the embryos of viable and nonviable wheat
      seeds as studied with the EPR spectroscopy of lipid-soluble spin labels.
AB  - Dried and hydrated embryos of wheat seeds (viable and nonviable, harvested in
      1992 and 1976, respectively) were studied by the EPR method with the use of the
      spin-labeling technique. Spin label Tempone was used for testing the plasmalemma
      integrity. It has been demonstrated that the loss of seed viability correlates
      with the loss of external membrane integrity. Spin-labeled derivatives of stearic
      acids, 5-doxylstearate I(12.3) and 16-doxylstearate I(1.14), were used to monitor
      the changes in structural characteristics of embryo cell membranes. The EPR
      spectra of these spin labels represent the superpositions of at least two signals
      from the molecules located in domains characterized by different fluidity. The
      comparison of the EPR spectra from I(12.3) in embryo cells and model systems
      (total fraction of lipids and purified seed oil) indicates that the majority of
      spin label molecules is located in the lipid surroundings, while the minor
      portion of I(12.3) is localized in so-called lipid bodies which contain seed oil.
      The embryo cells of viable and nonviable seeds differ in the sizes of these
      'solid' and 'fluid' intracellular domains. The environment of spin label
      molecules located in cell membranes of nonviable seeds is more rigid, as compared
      with that in the membranes of the viable cells. The study of dehydration
      rehydration effects has demonstrated that the loss of water causes the
      restriction of spin label mobility in embryo cells from both kinds of seeds.

PMID- 8142441
TI  - Interaction of merocyanine 540 with nicotinic acetylcholine receptor membranes
      from Discopyge tschudii electric organ.
AB  - Interactions between merocyanine 540 (MC540) and nicotinic acetylcholine receptor
      (AChR) have been studied by visible absorption spectroscopy using native receptor
      rich membranes from Discopyge tschudii electric tissue and liposomes obtained by
      aqueous dispersion of endogenous lipids extracted from the same tissue. The fact
      that merocyanine partitions into the membrane when this is in the liquid
      crystalline state, exhibiting a characteristic peak at 567 nm, was exploited to
      obtain quantitative information about the physical state of the AChR-rich
      membrane. Spectra of MC540 revealed that this molecule was preferentially
      incorporated into AChR-rich membranes, with an affinity (Kdapp 30 microM) 10-fold
      higher than that in liposomes (Kdapp 290 microM). Changes were observed in the
      equilibrium dissociation constant of MC540 at different temperatures: the two
      fold higher affinity at 8 degrees C than at 23 degrees C can be rationalized in
      terms of a higher value of the overall dimerization constant (Kdim) at the lower
      temperature. The local anaesthetic benzocaine competed for MC540 binding sites
      with higher potency in AChR-rich native membranes than in liposomes made with
      endogenous lipids. This competition was found to be AChR concentration-dependent,
      whereas in liposomes the displacement was constant at different lipid/MC540 molar
      ratios. Titration experiments yielded an apparent dissociation constant for
      benzocaine of 0.6 mM and 0.7 mM for liposomes and AChR-rich membranes,
      respectively. The possible location of the benzocaine binding site is deduced
      from the competition experiments to be at the lipid annulus surrounding the
      nicotinic AChR protein.

PMID- 8142442
TI  - Potent and reversible interaction of silver with pure Na,K-ATPase and Na,K-ATPase
      liposomes.
AB  - The Na,K-ATPase (EC 3.6.1.37) is the receptor for cardioactive steroids, the only
      specific inhibitors known at the present time for this unique membrane bound
      transport system. We report here that silver is the most rapid and potent
      inhibitor of isolated Na,K-ATPase ever described. Inhibition of Na,K-ATPase
      activity by silver is immediate and strikingly distinct from other inhibitors:
      addition of 1 mM of cysteine or DMPS reactivates the silver blocked-enzyme
      immediately. The results reveal that silver interacts with Na,K-ATPase and
      inhibits differently by an on-off mechanism involving most likely a few critical
      sulfhydryl groups. Inhibition of Na-K transport by silver has been demonstrated
      also in an artificial membrane, e.g., in liposomes reconstituted with pure Na,K
      ATPase performing active transport. Silver inhibits the active 86Rb transport
      mediated by the pure Na,K-ATPase molecule. The Na,K-ATPase contained in the
      liposomes was labeled specifically with 110mAg and appeared to bind two silver
      ions. Taken together, the results show that the mechanism of silver interaction
      with Na,K-ATPase might be different from other metals, for instance, mercury. The
      unique action mechanism of silver suggests a fundamental role of a few critical
      sulfhydryl groups for Na,K-transport.

PMID- 8142443
TI  - Lipid and protein composition of exovesicles released from human erythrocytes
      following treatment with amphiphiles.
AB  - Human erythrocytes were treated with different water-soluble amphiphiles
      (detergents) at sublytic concentrations, whereafter released exovesicles and
      treated cells were isolated. Lipid analyses showed that exovesicles had a lower
      cholesterol/phospholipid ratio and a higher phosphatidylserine/phospholipid ratio
      compared to parent cells. Protein analyses revealed that exovesicles were,
      relative to their total protein content, depleted in spectrin, actin and band 6
      protein and enriched in band 3 protein and acetylcholinesterase. Exovesicles
      contained all major glycoproteins. By using a radiolabeled amphiphile
      ([14C]cetyltrimethylammonium bromide) it was shown that the
      amphiphile/phospholipid ratio was similar in the vesicle membrane and in the
      parent cell membrane. This indicates that no significant segregation of the
      intercalated amphiphile between the exovesicle membrane and the parent cell
      membrane occurs during the vesiculation process. It is suggested that the
      redistributions of membrane lipids and proteins during the vesiculation process
      are secondary to the detachment of the cytoskeletal network from the membrane.

PMID- 8142444
TI  - Packing of a triacylglucolipid from the membrane of Acholeplasma laidlawii strain
      A at the air/water interface.
AB  - Pressure-area curves were generated at 22 degrees C and 40 degrees C for three
      glucolipids isolated from Acholeplasma laidlawii strain A-EF22. The glucolipids
      are 1,2-diacyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerol (MGlcDAG), 1,2-diacyl-3-O
      [alpha-D-glucopyranosyl-(1-->2)-O-alpha-D- glucopyranosyl]-sn-glycerol (DGlcDAG),
      and 1,2-diacyl-3-O-[3-O-acyl-(alpha-D-glucopyranosyl)]-sn- glycerol (MAMGlc-DAG).
      The curves for MGlcDAG and DGlcDAG are characteristic for monolayers in a liquid
      phase at both temperatures. MGlcDAG has a smaller molecular area at all surface
      pressures compared to DGlcDAG. At 22 degrees C MAMGlcDAG shows a phase transition
      at 13 mN/m. However, at 40 degrees C the pressure-area curve for this lipid is
      characteristic for a monolayer in a liquid state. Mixed MAMGlcDAG-DGlcDAG and
      MGlcDAG-DGlcDAG monolayers showed no significant deviation from the additivity
      rule at 40 degrees C. The area per acyl chain is nearly the same for MAMGlcDAG
      and MGlcDAG. Our study supports our previous results that aqueous dispersions of
      these lipids form non-lamellar, reversed aggregates.

PMID- 8142446
TI  - Tripeptide transport in rat lung.
AB  - Transport of L-alanyl-D-phenylalanyl-L-alanine was investigated with an in situ
      vascular perfusion preparation of rat lung and brush border membrane vesicles
      prepared from type II pneumocytes. In the perfused lung 1 mM tripeptide was
      transported intact from the alveolar lumen to the vascular perfusate at a mean
      rate of 25.1 +/- 1.29 (3) nmol/min per g dry weight. D-Phenylalanine also
      appeared in the vascular perfusate at a rate of 21.9 +/- 1.74 (3) nmol/min per g
      dry weight indicating that 47% of the absorbed tripeptide was split during
      passage across the epithelial layer. No dipeptide could be detected in the
      vascular effluent during perfusions with tripeptide. Rapid L-alanyl-D
      phenylalanyl-L-alanine uptake occurred with fresh apical membrane vesicles
      prepared from type II pneumocytes and this was abolished by treatment with 0.1%
      triton. The related tripeptide, D-alanyl-L-phenylalanyl-D-alanine, was taken up
      significantly more slowly by the vesicles. D-phenylalanyl-L-alanine and D
      phenylalanyl-D-alanine, were also studied with the vascularly perfused
      preparation; the mixed dipeptide appeared in the vascular perfusate significantly
      faster than L-alanyl-D-phenylalanyl-L-alanine whereas D-phenylalanyl-D-alanine
      appeared more slowly and was not hydrolysed.

PMID- 8142445
TI  - Local anesthetics destabilize lipid membranes by breaking hydration shell:
      infrared and calorimetry studies.
AB  - Differential scanning calorimetry (DSC) showed that local anesthetics decreased
      the pretransition (L beta'-->P beta') temperature of
      dipalmitoylphosphatidylcholine (DPPC) vesicle membranes four- to five-fold more
      than the main transition (P beta'-->L alpha) temperature. Because pretransition
      is mainly a change in the hydrophilic head property (tilted-rippled), the
      stronger effect on the pretransition suggests that the primary action site of
      local anesthetics is the lipid-water interface. The interfacial effect was
      analyzed by Fourier-transform infrared spectroscopy (FTIR) in water-in-oil (CCl4)
      reversed micelles. FTIR showed that the local anesthetics released hydrogen
      bonded water molecules from the phosphate (P = O bands) and glycerol (sn-2 C = O)
      moieties. The N-H stretching band of the local anesthetics was deconvoluted into
      two bands: hydrogen bonded to the phosphate moiety of the lipid and free (unbound
      to lipid). The formation constants between lipid P = O and anesthetic N-H were
      estimated in CCl4 from the spectral changes: 110 M-1 for lidocaine and 250 M-1
      for dibucaine. This small difference in the formation constants cannot explain
      the ten-fold stronger effect on the phase-transition temperature of dibucaine
      over lidocaine. By comparing the local anesthetic adsorption to the air/water
      interface in the presence and absence of lipid monolayers, we have previously
      shown (Lin et al. (1980) Biochim. Biophys. Acta 598, 51-65) that lipid
      anesthetics interaction involves three forces: lipophilic effect, hydrophobic
      effect, and anesthetic-anesthetic interaction. The anesthetic potency depends
      mainly on the hydrophobic effect (the difference in the standard molar free
      energies of local anesthetics in water and at the interface) and anesthetic
      anesthetic interaction energy. The anesthetic-anesthetic interaction means
      cooperativity of local anesthetics for the interfacial density: local anesthetics
      condense at the membrane surface when there are enough anesthetic molecules
      present at the interface to attract more anesthetics. The present data suggest
      that anesthetic action is directed to the interface between water and
      macromolecule, whether it is lipid membranes or proteins.

PMID- 8142448
TI  - Inhibition by cyclic AMP and phorbol esters of sodium-dependent uptake of
      phosphate by rat hepatocytes.
AB  - Na(+)-dependent phosphate uptake by rat hepatocytes in primary culture is
      inhibited in a time-dependent fashion by cyclic AMP and by the myristate, acetate
      ester of phorbol. After incubation for 15 min at 37 degrees C with 10(-7) M
      dibutyryl cAMP, the Vmax of transport is decreased from 0.52 to 0.23 nmol Pi/min
      per mg protein but the Km value of approximately 1 mM is hardly affected by the
      treatment. Thus, physiological control of Pi uptake by liver cells probably
      involves protein phosphorylation(s) catalysed by protein kinases. Protein kinase
      C may be important but the relatively high concentration of phorbol ester needed
      to cause inhibition of transport is not convincing evidence for protein kinase C
      involvent. In the presence of fructose, the rate of Pi uptake is decreased by
      50%. This effect is probably secondary to a depletion of cellular ATP.

PMID- 8142447
TI  - Effect of sterol side-chain structure on sterol-phosphatidylcholine interactions
      in monolayers and small unilamellar vesicles.
AB  - In this study we have characterized the monolayer behavior of analogues of
      cholesterol having different side-chain structures and their interaction with
      phosphatidylcholines in mixed monolayers and small unilamellar vesicles (SUVs).
      Two series of side-chain analogues of cholesterol were synthesized, one with an
      unbranched side chain (the n-series, from 3 to 7 carbons in length), and the
      other with a single methyl-branched side chain (the iso-series, from 5 to 10
      carbons in length). The length and conformation of the sterol side chain markedly
      influenced both the mean molecular area of the pure sterols and their monolayer
      stability (i.e., collapse pressure). Shorter side chains gave smaller mean
      molecular areas and decreased monolayer stability. The sterols from the n-series
      also had smaller mean molecular areas than the corresponding sterols in the iso
      series. In mixed 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/sterol
      monolayers (equimolar ratio; at 22 degrees C), all of the sterols tested
      decreased the monolayer stability as judged by the lower collapse pressure with
      sterol than without sterol. A similar trend was observed in mixed monolayers
      containing 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), except that
      sterols from the iso-series with a chain length of 8 or 10 carbon atoms actually
      stabilized the monolayer compared with the sterol-free SOPC monolayer. The
      ability of the sterols to condense the molecular packing of DPPC was similar with
      all sterols (3-5% condensation at 10 mN/m), irrespective of the length or
      structure of the side chain. 5-Androsten-3 beta-ol, however, which lacks the side
      chain, did not at all condense the monolayer packing of DPPC. With SOPC mixed
      monolayers, all side chain containing sterols caused a 18-20% condensation (at 10
      mN/m) of monolayer packing. The condensing effect of 5-androsten-3 beta-ol on
      SOPC packing was again much smaller (about 10%) compared with that of the side
      chain sterols. The rate of sterol oxidation by cholesterol oxidase (at 37 degrees
      C) in DPPC-containing SUVs increased as a function of increasing the side-chain
      length (iso-series). With sterols from the n-series, the same trend was seen,
      except that the n-C7 analogue was oxidized much slower than the n-C4, n-C5, and n
      C6 analogues. With SOPC SUVs, a similar side-chain dependent oxidation pattern
      was observed. Our results support and extend previous knowledge about the
      importance of the sterol side chain in determining sterol-sterol and sterol
      phospholipid interactions, both in mono- and bilayers.

PMID- 8142449
TI  - Differential effects of brefeldin A on hormonally regulated Na+ transport in a
      model renal epithelial cell line.
AB  - Na+ transport in renal epithelia is regulated by a wide variety of endogenous and
      exogenous cellular factors. Although most natriferic agents have an action on the
      amiloride-sensitive Na+ channel, the biochemical pathways which precede
      activation of the channel remain incompletely defined. One approach to dissecting
      such intricate pathways is to perturb a specific cellular process and determine
      its importance in the postulated mechanism. The current studies examine the
      effect of brefeldin A (BFA), an inhibitor of the central vacuolar system, on
      basal as well as aldosterone-, insulin-, and forskolin-stimulated Na+ transport.
      In the A6 cell line, BFA had a time-dependent effect on basal transport.
      Aldosterone-induced Na+ transport was sensitive to BFA while insulin's action was
      only partially blocked and forskolin-stimulated Na+ transport was relatively
      resistant to the action of the inhibitor. These studies highlight differences as
      well as points of convergence in the natriferic pathways.

PMID- 8142450
TI  - Cloning and sequencing of an Na+/H+ antiporter gene from the marine bacterium
      Vibrio alginolyticus.
AB  - A gene has been cloned from a DNA library from the marine bacterium Vibrio
      alginolyticus that functionally complements a mutant strain of Escherichia coli,
      NM81, defective in an Na+/H+ antiporter (NhaA). The cloned Vibrio gene restored
      NM81 to grow in a medium containing 0.5 M NaCl at pH 7.5 and concomitantly led to
      an increase in Na+/H+ antiport activity. The nucleotide sequence of the cloned
      fragment revealed an open reading frame, which encodes a protein with a predicted
      383 amino acid sequence and molecular mass of 40,400 Da. The hydropathy profile
      is characteristic of a membrane protein with 11 membrane spanning regions. The
      deduced amino acid sequence is 58% identical with E. coli NhaA.

PMID- 8142451
TI  - cDNA sequence for rkST1, a novel member of the sodium ion-dependent glucose
      cotransporter family.
AB  - A full length cDNA for rkST1, a novel member of the Na+/glucose cotransporter
      family, was cloned from rabbit kidney and sequenced. The coding sequence
      comprised 2022 base pairs and 674 amino acids. rkST1 beared 50-60% amino acid
      identity to the other cotransporters and was characteristic in respect of its
      expression in brain in addition to kidney among the cotransporters.

PMID- 8142452
TI  - Red cell membrane protein band 4.2: phenotypic, genetic and electron microscopic
      aspects.
AB  - The present status of band 4.2 has been reviewed from the standpoint of protein
      chemistry, gene analysis and clinical hematology. Band 4.2 plays an important
      role in various cellular functions. In 142 GCT-->ACT band 4.2 deficiency,
      abnormalities of the cytoskeletal network were clearly observed by electron
      microscopy and by ektacytometry, although the cytoskeletal proteins themselves
      were essentially normal in these red cells. The physiological states of band 3 in
      situ in the membranes were also affected in band 4.2 deficiency, as detected by
      electron microscopy, although again the biochemical properties of band 3 itself
      were essentially normal in these red cells. Other disorders of band 4.2
      deficiency in the absence of the 142 GCT-->ACT mutation appear to be most
      interesting in the pathogenesis of hemolysis. In some of the band 4.2 anomalies,
      other membrane proteins including band 3 would appear to be most pathognomonic
      for the disease states. These conditions require elucidation by protein chemistry
      and gene analysis. The control mechanism of the gene expression should also be
      clarified to understand the important role of band 4.2 in health and disease.

PMID- 8142453
TI  - Cytosolic proteins of 21-23 kDa are methylated by kidney cortex membrane
      associated C-terminal carboxyl methyltransferases.
AB  - We have studied the effect of a soluble fraction from kidney cortex on the C
      terminal carboxyl methylation of 21-23 kDa proteins catalyzed by membrane
      associated methyltransferases. Addition of soluble proteins to isolated luminal,
      antiluminal and intracellular membranes resulted in a large increase in the
      methylation of the membrane-associated 21-23 kDa substrates. Fractionation of the
      soluble extract from the cortex by Q-Sepharose anion exchange chromatography
      showed the presence of two distinct peaks of proteins presenting stimulating
      activities, eluting at 0.15 M (peak I) and 0.4 M (peak II) NaCl, respectively.
      Both peaks eluted as proteins of apparent molecular sizes of 40 kDa upon Superose
      6 gel-filtration chromatography. No methylation activity towards N-acetyl-S
      trans,trans-farnesylcysteine (AFC), a good substrate for C-terminal carboxyl
      methyltransferases, was associated with either peaks. In contrast, the increase
      in methylation induced by these proteins was strongly inhibited by AFC,
      suggesting that the methylation induced by these factors occurred on C-terminal
      isoprenylated cysteine residues. Both partially purified proteins competitively
      inhibited the methylation of AFC by the membrane-associated enzymes, suggesting
      that they may represent substrates for the methyltransferases. Immunoblotting of
      these partially purified soluble substrates with a rabbit polyclonal antibody
      directed against the small G-protein CDC42 showed the presence of this protein in
      peak I but not in peak II. Taken together, these results suggest the presence in
      a soluble fraction from the kidney of distinct methyl-accepting proteins, one of
      these being tentatively identified as the small G-protein CDC42.

PMID- 8142454
TI  - Simultaneous racemization and isomerization at specific aspartic acid residues in
      alpha B-crystallin from the aged human lens.
AB  - We provide evidence that the racemization and isomerization of aspartyl(Asp)
      residues occur simultaneously in the alpha B-crystallin in the lens of aged (mean
      age: 80 years) and young (age: 11 months) humans. We purified alpha B-crystallin
      and subjected it to tryptic digestion. The resulting peptides were separated by
      reverse-phase high-performance chromatography (RP-HPLC) and were characterized by
      amino-acid composition, sequence analysis and mass spectrometry. Two specific
      sites, Asp-36 (D/L of Asp: 0.92) and Asp-62(D/L of Asp: 0.57), among 13
      Asp/asparginyl (Asn) residues in aged alpha B-crystallin, were found to be highly
      racemized and isomerized to form beta-Asp residues. The beta-Asp-containing
      peptides were clearly distinguished from normal Asp-containing (alpha-Asp)
      peptides by RP-HPLC. The racemization and isomerization of Asp residues in aged
      alpha B-crystallin may occur via a succinimide intermediate. In young alpha B
      crystallin, we observed neither racemization nor isomerization. We also found
      that Met-68 was oxidized to form Met sulfoxide to a greater extent in aged alpha
      B-crystallin than in young alpha B-crystallin. We concluded that racemization,
      isomerization, and oxidation of alpha B-crystallin occur spontaneously in the
      aging process.

PMID- 8142455
TI  - Chemical modification of xylanase from alkalothermophilic Bacillus species:
      evidence for essential carboxyl group.
AB  - The role of carboxyl group in the catalytic action of xylanase (M(r) 35,000) from
      an alkalothermophilic Bacillus sp. was delineated through kinetic and chemical
      modification studies using Woodward's Reagent K. The kinetics of inactivation
      indicated that one carboxyl residue was essential for the xylanase activity with
      a second order rate constant of 3300 M-1 min-1. The spectrophotometric analysis
      at 340 nm revealed that the inhibition was correlated with modification of 24
      carboxyl residues. In the presence of protecting ligand, modification of one
      carboxyl group was prevented. The pH profile showed apparent pK values of 5.2 and
      6.4 for the free enzyme and 4.9 and 6.9 for enzyme-substrate complex. The pH
      dependence of inactivation was consistent with the modification of carboxyl
      group. The kinetic analysis of the modified enzyme showed similar Km and lower
      kcat values than the native enzyme indicating that catalytic hydrolysis and not
      the substrate binding was affected by chemical modification. The chemical
      modification of xylanase from alkalothermophilic Bacillus revealed the presence
      of tryptophans in the active site (Deshpande, V, Hinge, J. and Rao, M. (1990)
      Biochim. Biophys. Acta 1041, 172-177). This finding and present studies
      demonstrated the experimental evidence for the participation of carboxyl as well
      as tryptophan groups as essential residues of xylanase from alkalothermophilic
      Bacillus sp.

PMID- 8142456
TI  - The synthesis of a pyridyl analog of adenosylcobalamin and its coenzymic function
      in the diol dehydratase reaction.
AB  - A novel analog of adenosylcobalamin in which 5,6-dimethylbenzimidazole and D
      ribose moieties of the nucleotide loop are replaced by pyridine and the
      trimethylene group, respectively, was synthesized and examined for coenzymic
      function. The coordination of pyridine to the cobalt atom in this analog was
      stronger than that of 5,6-dimethylbenzimidazole in the corresponding homolog. The
      adenosyl form of pyridyl analog served as partially active coenzyme for diol
      dehydratase. The kcat/Km values calculated from the initial velocity indicate
      that this analog is a better coenzyme than the 5,6-dimethylbenzimidazolyl or
      imidazolyl counterpart. However, the reaction with the pyridyl analog as coenzyme
      was accompanied with a concomitant inactivation during catalysis, with a
      kcat/Kinact value 50-100 times lower than that for adenosylcobalamin or the 5,6
      dimethylbenzimidazolyl analog. Therefore, it can be concluded that the 5,6
      dimethylbenzimidazole moiety of adenosylcobalamin is important for continuous
      progress of a catalytic cycle by protecting the reactive intermediates from side
      reactions.

PMID- 8142457
TI  - Alpha,beta-unsaturated carbonyl compounds: inhibition of rat liver glutathione S
      transferase isozymes and chemical reaction with reduced glutathione.
AB  - Five different alpha,beta-unsaturated carbonyl compounds displayed different
      reactivities with regard to inhibition of alpha- and mu-class isozymes of rat
      liver glutathione S-transferases and the chemical reaction with glutathione. Only
      (E)-2-octenal and (E)-3-nonen-2-one exhibited significant levels of inhibition
      for each of the rat liver GST isozymes examined. The (E)-2-octenal was more
      effective as an inhibitor of the alpha-class of isozymes when compared to the mu
      class, whereas the (E)-3-nonen-2-one showed a greater degree of inhibition of the
      mu-class of isozymes relative to the alpha-class. Isozyme 1-1 demonstrated the
      greatest degree of inhibition with (E)-2-octenal (IC50 = 5.89 microM) of all
      inhibitor/isozyme combinations. The Ki values for (E)-2-octenal and (E)-3-nonen-2
      one toward selected alpha- and mu-class of rat liver glutathione S-transferase
      isozymes were determined and both of these compounds competitively inhibited all
      five of the rat liver glutathione S-transferase isozymes examined. The Ki values
      obtained for these two compounds were significantly different for each of the
      isozymes except for isozyme 4-4. With the alpha-class of rat liver GST isozymes,
      (E)-3-nonen-2-one showed a larger Ki value than (E)-2-octenal. Whereas, with the
      mu-class, (E)-2-octenal exhibited a larger Ki value than (E)-3-nonen-2-one. The
      rate constants of the forward reaction (k+1), as well as the equilibrium
      constants (Kd) were determined and the rate constants of the reverse reaction (k
      1) were calculated.

PMID- 8142458
TI  - Assessment of homology with the helical mimicry algorithm.
AB  - Homologies based on structural motifs characterize conserved structures and
      mechanisms of maintaining function. An algorithm was developed to quantitate
      homology among segments of two proteins based upon structural characteristics of
      an amphipathic alpha-helix. This helical mimicry algorithm scored homology among
      sequences of two proteins in terms of: (i) presence of Leu, Ile, Val, Phe, or Met
      in a longitudinal, hydrophobic strip-of-helix at positions n, n + 4, n + 7, n +
      11, etc. in the primary sequence, (ii) identity or chemical similarity of amino
      acids at intervening positions and (iii) exchanges of amino acids from positions
      n to n - 1, n + 3, n + 4, n + 1, n - 3, n - 4 around n (on the surface of a
      putative helix). While such exchanges of amino acids on the surfaces of
      homologous helices may conserve function, they did not maintain specific
      interactions of those residues with apposing groups.

PMID- 8142459
TI  - Amino-acid sequence of a trypsin/chymotrypsin inhibitor from giant taro (Alocasia
      macrorrhiza).
AB  - Giant taro (Alocasia macrorrhiza) contains a protein which inhibits both trypsin
      and chymotrypsin. This trypsin/chymotrypsin inhibitor exists as a dimer of two
      identical monomers each with slight polymorphism and is an attractive candidate
      for conferring insect resistance in transgenic plants. The 184 amino-acid
      sequence (molecular mass of 19774 Da for the Met-24, Glu-50 form) has been
      determined and is compared with those of other Kunitz-type trypsin, chymotrypsin
      and subtilisin inhibitors. There appears to be greater 'homology' between the
      giant taro inhibitor and those inhibitors from other monocotyledons than
      inhibitors from dicotyledons. The P1 loop region is different from that of other
      Kunitz-type inhibitors and contains a sequence Leu-Ala-Phe-Phe-Pro at residues 56
      60. This section of sequence differs only by a Leu/Ile replacement to a tight
      binding inhibitor of neutrophil elastase, recently produced by genetic
      engineering. The most likely candidate for the P1 residue in the giant taro
      trypsin/chymotrypsin inhibitor is Leu-56.

PMID- 8142460
TI  - Alpha-crystallin: molecular chaperone and protein surfactant.
AB  - Bovine lens alpha-crystallin has recently been shown to function as a molecular
      chaperone by stabilizing proteins against heat denaturation (Horwitz, J. (1992)
      Proc. Natl. Acad. Sci. USA, 89, 10449-10453). An investigation, using a variety
      of physico-chemical methods, is presented into the mechanism of stabilization.
      alpha-Crystallin exhibits properties of a surfactant. Firstly, a plot of
      conductivity of alpha-crystallin versus concentration shows a distinct inflection
      in its profile, i.e., a critical micelle concentration (cmc), over a
      concentration range from 0.15 to 0.17 mM. Gel chromatographic and 1H-NMR
      spectroscopic studies spanning the cmc indicate no change in the aggregated state
      of alpha-crystallin implying that a change in conformation of the aggregate
      occurs at the cmc. Secondly, spectrophotometric studies of the rate of heat
      induced aggregation and precipitation of alcohol dehydrogenase (ADH), beta L- and
      gamma-crystallin in the presence of alpha-crystallin and a variety of synthetic
      surfactants show that stabilization against precipitation results from
      hydrophobic interactions with alpha-crystallin and monomeric anionic surfactants.
      Per mole of subunit or monomer, alpha-crystallin is the most efficient at
      stabilization. alpha-Crystallin, however, does not preserve the activity of ADH
      after heating. After heat inactivation, gel permeation HPLC indicates that ADH
      and alpha-crystallin form a high molecular weight aggregate. Similar results are
      obtained following incubation of beta L- and gamma-crystallin with alpha
      crystallin. 1H-NMR spectroscopy of mixtures of alpha- and beta L-crystallin, in
      their native states, reveals that the C-terminus of beta B2-crystallin is
      involved in interaction with alpha-crystallin. In the case of gamma- and alpha
      crystallin mixtures, a specific interaction occurs between alpha-crystallin and
      the C-terminal region of gamma B-crystallin, an area which is known from the
      crystal structure to be relatively hydrophobic and to be involved in
      intermolecular interactions. The short, flexible C-terminal extensions of alpha
      crystallin are not involved in specific interactions with these proteins. It is
      concluded that alpha-crystallin interacts with native proteins in a weak manner.
      Once a protein has become denatured, however, the soluble complex with alpha
      crystallin cannot be readily dissociated. In the aging lens this finding may have
      relevance to the formation of high molecular weight crystallin aggregates.

PMID- 8142461
TI  - Resonance Raman spectroscopic studies of ligated mutant myoglobins.
AB  - Ligand binding (CO and N3-) to wild-type porcine myoglobin and to several mutant
      forms, expressed and purified from E. coli cells, has been studied using Raman
      spectroscopy. The v(Fe-CO) stretching vibration in MbIICO has been compared for
      the wild-type and mutant proteins. This gives a broad band consisting of five
      components, indicating five possible configurations of the bound CO. The distal
      pocket mutants show large variations in bandshape, the major component occurring
      at progressively lower wavenumber in the order: wild-type (WT) > E11 Val-->Thr
      (VT) > E7 His-->Val (HV) > the double mutant VT/HV (M2). Changes observed in the
      Raman band assigned to the azide bending mode in MbIIIN3 have been interpreted in
      terms of resonance structures involving two forms of azide binding. Repulsion
      between the bound azide ligand and the OH group of the adjacent thr residue in
      the VT mutant, and a shorter Fe-N(his) bond in the proximal mutant Ser-->Leu
      (F7), both affect this bonding. In the wild-type protein (WT),
      hydroxymetmyoglobin exists in a spin-state equilibrium which, at room
      temperature, is predominantly high-spin. In the F7 mutant this equilibrium is
      shifted in favour of the low-spin form. A low-spin iron species also exists in
      the aquometmyoglobin form of this mutant.

PMID- 8142462
TI  - Transhydroxylase of Pelobacter acidigallici: a molybdoenzyme catalyzing the
      conversion of pyrogallol to phloroglucinol.
AB  - Trihydroxybenzenes are degraded anaerobically through the phloroglucinol pathway.
      In Pelobacter acidigallici as well as in Pelobacter massiliensis, pyrogallol is
      converted to phloroglucinol in the presence of 1,2,3,5-tetrahydroxybenzene by
      intermolecular hydroxyl transfer. The enzyme catalyzing this reaction was
      purified to chromatographic and electrophoretic homogeneity. Gel filtration and
      electrophoresis revealed a heterodimer structure with an apparent molecular mass
      of 127 kDa for the native enzyme and 86 kDa and 38 kDa, respectively, for the
      subunits. The enzyme was not sensitive to oxygen. HgCl2, p-chloromercuribenzoic
      acid, and CuCl2 inhibited strongly the reaction indicating an essential function
      of SH-groups. Transhydroxylase had a pH-optimum of 7.0 and a pI of 4.1. The
      apparent temperature optimum was in the range of 53 degrees C to 58 degrees C.
      The activation energy for the conversion of pyrogallol and 1,2,3,5
      tetrahydroxybenzene to phloroglucinol and tetrahydroxybenzene was 31.4 kJ per
      mol. Purified enzyme exhibited a specific activity of 3.1 mol min-1 mg-1 protein
      and an apparent Km for pyrogallol and 1,2,3,5-tetrahydroxybenzene of 0.70 mM and
      0.71 mM, respectively. The enzyme was found to contain per mol heterodimer 1.1
      mol molybdenum, 12.1 mol iron and 14.5 mol acid-labile sulfur. Requirement for
      molybdenum for transhydroxylating enzyme activity was proven also by cultivation
      experiments. No hints for the presence of flavins were obtained. The results
      presented here support the hypothesis that a redox reaction is involved in this
      intermolecular hydroxyl transfer.

PMID- 8142463
TI  - Fluorescence dynamics of staphylococcal nuclease in aqueous solution and reversed
      micelles.
AB  - The dynamical fluorescence properties of the sole tryptophan residue (Trp-140) in
      Staphylococcus aureus nuclease (EC 3.1.31.1) have been investigated in aqueous
      solution and reversed micelles composed of either sodium bis(2
      ethylhexyl)sulfosuccinate (AOT) in isooctane or cetyltrimethylammonium chloride
      (CTAC) in isooctane/hexanol (12:1 by volume). The fluorescence decay of nuclease
      in the different environments can be described by a trimodal distribution of
      fluorescence lifetimes at approx. 0.5, 1.5 and 5.0 ns. The relative amplitudes
      depend on the environment. For pH 9.0 solutions the contribution of the two
      shortest lifetime components in the distribution is largest for AOT and smallest
      for CTAC reversed micelles. There is reasonable agreement between the average
      fluorescence lifetime and the fluorescence quantum efficiency confirming a
      significant fluorescence quenching in AOT reversed micelles. Fluorescence
      anisotropy decay revealed that the tryptophan environment in aqueous nuclease
      solutions is rigid on a nanosecond timescale. When nuclease was entrapped into
      reversed micelles the tryptophan gained some internal flexibility as judged from
      the distinct presence of a shorter correlation time. The longer correlation time
      reflected the rotational properties of the protein-micellar system. Modulation of
      the overall charge of nuclease (isoelectric point pH 9.6) by using buffer of pH
      9.0 and pH 10.4, respectively, and of the size of empty micelles by selecting two
      values of the water to surfactant molar ratio, had only a minor effect on the
      rotational properties of nuclease in the positively charged reversed micelles.
      Encapsulation of nuclease in anionic reversed micelles resulted in the
      development of protein bound to aggregated structures which are immobilised on a
      nanosecond timescale. According to far UV circular dichroism results the
      secondary structure of nuclease only followed the already published pH-dependent
      changes. Encapsulation had no major effect on the overall secondary structure.

PMID- 8142464
TI  - Functional properties of recombinant staphylokinase variants obtained by site
      specific mutagenesis of methionine-26.
AB  - Variants of recombinant staphylokinase (Sak) were produced by site-specific
      mutagenesis of the unique Met-26 residue and purified to homogeneity from the
      cell extract of transformed E. coli. The desired mutations were confirmed by cDNA
      and amino-acid sequence analysis. Sak-M26L, Sak-M26C, Sak-M26R, Sak-M26V and Sak
      M26A were selected for further analysis on the basis of their plasminogen
      activating activity. The specific fibrinolytic activities of Sak-M26L, Sak-M26C
      and Sak were comparable (76,000 +/- 10,000, 75,000 +/- 2400 and 78,000 +/- 9700
      HU/mg, respectively; mean +/- S.E., n = 3 or 4). Active site exposure in
      equimolar (4.5 microM) mixtures plasminogen at room temperature was more rapid
      with Sak-M26L than with Sak (quantitative exposure within 4 min and 8 min,
      respectively). Activation of 1 microM plasminogen by catalytic amounts (5 nM) of
      Sak-M26L initially appeared to be somewhat faster, but comparable 50 to 60%
      activation was obtained within 30 min. In contrast, Sak-M26R and Sak-M26V were
      virtually inactive, did not form active complexes with plasminogen and did not
      activate plasminogen. The catalytic efficiencies for plasminogen activation were
      comparable for plasmin-Sak-M26L, plasmin-Sak-M26C and plasmin-Sak (0.14 microM-1
      s-1, 0.16 microM-1 s-1 or 0.12 microM-1 s-1, respectively). Comparable dose
      dependent lysis of 0.06 ml 125I-fibrin labeled human plasma clots submerged in
      0.3 ml human plasma was obtained with Sak-M26L, Sak-M26C and Sak (concentration
      required for 50% lysis in 2 h, EC50, of 17 +/- 1.6 nM, 19 +/- 1.4 nM and 14 +/-
      2.5 nM, respectively), whereas Sak-M26R or Sak-M26V were inactive. Sak-M26A did
      not form a stable complex with plasminogen, as shown by gel filtration. These
      data establish that substitution of the unique Met residue in position 26 of the
      Sak sequence with Leu or Cys has little or no influence on its plasminogen
      activating or fibrinolytic potential. In contrast, substitution of Met-26 with
      either Arg or Val results in total loss of the functional activity. Thus, the
      amino acid in position 26 of Sak appears to be of crucial importance for the
      activation of plasminogen by staphylokinase.

PMID- 8142465
TI  - Purification of selenoprotein P from human plasma.
AB  - Selenoprotein P was partially purified (> 1000-fold) from human plasma in four
      chromatographic steps using 75Se-labeled selenoprotein P secreted by HepG2 cells
      in culture as a marker. The purified preparation was injected into mice and
      monoclonal antibodies, which precipitated the labeled protein, were generated.
      Neither of two different monoclonal antibodies had cross-reactivity with plasma
      from five animal species. Antibodies were coupled to agarose, and selenoprotein P
      was purified from human plasma by immunoaffinity chromatography followed by
      chromatography on heparin agarose. With two different matrix-bound monoclonal
      antibodies, the purification procedure gave two bands on SDS-PAGE with mobilities
      corresponding to 61 and 55 kDa. Both bands stained for carbohydrate and showed
      increased electrophoretic mobility after enzymatic deglycosylation.
      Immunoaffinity chromatography removed approx. one-third of the selenium from
      plasma or 0.4 mumol Se/l at a total selenium concentration of 1.1 mumol/l,
      indicating that selenoprotein P constituted this proportion of total plasma
      selenium in healthy US blood donors.

PMID- 8142466
TI  - The regulation of alanine and aspartate aminotransferase by different aminothiols
      and by vitamin B-6 derivatives.
AB  - We examined the effects on alanine aminotransferase and aspartate
      aminotransferase of different aminothiols (L-cysteine, D-cysteine, cysteamine, L
      cysteine ethyl ester, L-cysteine methyl ester) and several vitamin B-6
      derivatives (pyridoxal, pyridoxamine, pyridoxol, pyridoxol 5'-phosphate), before
      and after treatment with KOCN, which transforms these molecules into the
      corresponding carbamoyl derivatives. Only GPT, and not GOT, was specifically
      inhibited by L-cysteine and, to a lesser extent, by D-cysteine. The association
      reaction: PLP + apo GPT<-->holo GPT was inhibited by the vitamin B-6 derivatives,
      and this inhibition was prevented by pretreatment of the vitamin B-6 derivatives
      with KOCN. All the observed effects occurred at pH 7, 37 degrees C, at mM and
      even lower concentrations of reagents. Hence, they all potentially play a
      physiological role, in the regulation of the PLP dependent enzymes and of the
      vitamin B-6 levels in the cell.

PMID- 8142467
TI  - Primary structure of aspergillopepsin I deduced from nucleotide sequence of the
      gene and aspartic acid-76 is an essential active site of the enzyme for
      trypsinogen activation.
AB  - The coding region of the aspergillopepsin I (EC 3.4.23.18) gene occupies 1340
      base pairs of the genomic DNA and is separated into four exons by three introns.
      The predicted amino-acid sequence of aspergillopepsin I consists of 325 residues
      and is 32% and 27% homologous with those of human pepsin and calf chymosin. The
      cDNA of the gene prepared from mRNA has been cloned and expressed in yeast cells.
      To identify the residue of the substrate binding pocket in determining the
      specificity of aspergillopepsin I towards basic substrates, this residue was
      replaced with a serine residue by site-directed mutagenesis. The mutation is a
      single amino-acid change, Asp-76 converted to Ser-D76S, in the enzyme. The
      striking feature of this is that only the trypsinogen activating activity was
      destroyed. We therefore concluded that Asp-76 is the binding site towards basic
      substrates.

PMID- 8142468
TI  - Human alpha-galactosidase gene expression: significance of two peptide regions
      encoded by exons 1-2 and 6.
AB  - Two proteins with alpha-galactosidase activity, alpha-galactosidase A (alpha
      GalA) and alpha-galactosidase B (alpha-GalB, or alpha-N-acetylgalactosaminidase;
      alpha-NAGA) have a high homology of amino-acid sequence. Point mutations of the
      alpha-GalA gene have been reported only in the exons 1, 2 or 6. In this study,
      the exon 1-2 and/or 6 sequences of alpha-GalA cDNA were partly substituted by the
      corresponding regions of alpha-GalB cDNA, and three chimeric proteins were
      prepared by the baculovirus expression system: CMB12 with substitution at the
      exon 1-2 region, CMB6 at the exon 6 region, and CMB126 at both regions. They all
      preserved alpha-GalA antigenicity. Their kinetic properties toward 4
      methylumbelliferyl alpha-galactopyranoside were compared with those of alpha
      GalA. The catalytic activity was slightly low in CMB12, decreased to 1/10 in
      CMB6, and restored to a significant degree in CMB126. Km was more than 4-fold
      higher for CMB6 and CMB126 than for alpha-GalA. The pH optimum was 4.0 for both
      CMB12 and alpha-GalA, 4.8 for CMB6, and 4.6 for CMB126 and alpha-GalB. The
      catalytic activity was inhibited most by galactosamine in CMB6, and less in alpha
      GalB, CMB126, alpha-GalA and CMB12 in decreasing order. The 50% inhibition
      concentrations of melibiose (Gal alpha 1-6Glc) and methyl alpha-galactopyranoside
      were 2.5- to 3-fold higher for CMB126 than for alpha-GalA. These results indicate
      that the low affinity of CMB126 to the substrate was caused by a reduced affinity
      to terminal alpha-linked galactose. We conclude that (1) the two regions encoded
      by exons 1-2 and 6 contribute to the alpha-galactosidic cleavage, and (2) an
      increase in Km of CMB6 or CMB126, with chimeric substitutions at the exon 6
      region, was caused by a loss of affinity toward terminal alpha-linked galactose.

PMID- 8142469
TI  - Novel structure of a Chinese hamster polyubiquitin gene.
AB  - We isolated a polyubiquitin gene, CHUB2, from the V79 Chinese hamster genomic
      library, and determined its complete structure. Based on sequence homology to the
      human polyubiquitin gene UbC in the 5' and 3' untranslated region, the CHUB2 gene
      was characterized as the V79 Chinese hamster equivalent to the human UbC gene.
      However, the overall coding region structure of the CHUB2 gene was altered from
      the consensus structure of polyubiquitin genes, with the last ubiquitin coding
      unit being followed by 161 bp of partially deleted and mutated ubiquitin-like
      sequence. Although a similarly deleted and mutated polyubiquitin gene was
      recently reported in a partially sequenced cDNA of mouse (Finch et al. (1992)
      Cell Growth Differ. 3, 269-278), the present study describes the complete
      sequence of a polyubiquitin gene containing this unusual structure for the first
      time, and suggests that this structure is conserved in rodents. By employing both
      Southern and Northern analysis with a probe specific to the CHUB2 gene, it was
      found that a second, closely related gene is present in the Chinese hamster
      genome, and that both loci are transcriptionally active in V79 cells. The two
      genes, and their respective transcripts, differ in size because of variation in
      the relative number of repeating ubiquitin coding units.

PMID- 8142470
TI  - A novel glutathione S-transferase isozyme similar to GST 8-8 of rat and mGSTA4-4
      (GST 5.7) of mouse is selectively expressed in human tissues.
AB  - A mouse glutathione S-transferase (GST) isozyme designated as GST 5.7 or mGSTA4-4
      belongs to a distinct subclass of the alpha-class isozymes of GST. It is
      characterized by kinetic properties intermediate between the alpha- and pi
      classes of GSTs. We have recently cloned and expressed this isozyme (rec-mGSTA4
      4) in E. coli and have reported its complete primary sequence (Zimniak, P., et
      al. (1992) FEBS Lett., 313, 173-176). Using antibodies raised against the
      homogenous rec-mGSTA4-4 expressed in E. coli, we now demonstrate that an ortholog
      of this isozyme was selectively expressed in various human tissues. The human
      ortholog of mGST A4-4 purified from liver had a pI value of 5.8 and constituted
      approx. 1.7% of total GST protein of human liver. Similar to other alpha-class
      GSTs, the N-terminus of this isozyme (GST 5.8) was also blocked. CNBr digestion
      of the enzyme yielded two major fragments with M(r) values of 12 kDa and 6 kDa.
      The sequences of these two fragments showed identities in 16 out of 20 residues
      and 17 out of 20 residues with the corresponding sequences of its mouse ortholog
      (mGSTA4-4), and showed significant homologies with the rat and chicken orthologs,
      GST 8-8 and GST CL3. Human liver GST 5.8 showed more than an order of magnitude
      higher activity towards t-4-hydroxy-2-nonenal as compared to 1-chloro-2,4
      dinitrobenzene. This isozyme also expressed glutathione-peroxidase activity
      towards fatty acid, as well as phospholipid hydroperoxides suggesting its role in
      protection mechanisms against the toxicants generated during lipid peroxidation.
      Western blot analysis of human tissues revealed that this GST isozyme was
      selectively expressed in human liver, pancreas, heart, brain and bladder tissues,
      but absent in lung, skeletal muscle, spleen and colon.

PMID- 8142471
TI  - Decorin and a large dermatan sulfate proteoglycan in bovine striated muscle.
AB  - Proteoglycans were extracted and isolated from adult bovine muscle tissue by
      dissociative extraction followed by density gradient centrifugation, gel
      chromatography and ion-exchange chromatography. Two proteoglycans were
      characterized; one of large molecular size (PG-L) and one of small molecular size
      (PG-S). The recovery of PG-L and PG-S was 33% and 67%, respectively. By cellulose
      acetate electrophoresis before and after treatment with chondroitinase AC and ABC
      both samples were shown to carry predominantly dermatan sulfate chains. The large
      proteoglycan was recognized with an antibody against a large dermatan sulfate
      proteoglycan from bovine sclera, whereas the small was recognized by an antibody
      against decorin from bovine sclera. Chondroitinase ABC treatment of PG-S followed
      by SDS-PAGE showed a core protein with a molecular weight of 45 kDa, which also
      reacted with the decorin antibody. Amino-acid analysis of both PG-L and PG-S
      revealed an amino-acid composition closely similar, although not identical, to
      the large dermatan sulfate proteoglycan from bovine sclera and decorin,
      respectively. Immunohistochemical analyses of muscle tissue sections showed that
      decorin and the large dermatan sulfate proteoglycan are present in the perimysium
      layers of muscle tissue, although although with a somewhat different pattern of
      distribution. Decorin was, in addition, found in the endomysium.

PMID- 8142472
TI  - Functional and structural membrane topology of rat liver microsomal glutathione
      transferase.
AB  - The membrane topology of rat liver microsomal glutathione transferase was
      investigated by comparing the tryptic cleavage products from intact and
      permeabilized microsomes. It was shown that lysine-4 of microsomal glutathione
      transferase is accessible at the luminal surface of the endoplasmic reticulum,
      whereas lysine-41 faces the cytosol. These positions are separated by a
      hydrophobic stretch of 25 amino acids (positions 11-35) which comprises the
      likely membrane-spanning region. Reaction of cysteine-49 of the microsomal
      glutathione transferase with the charged sulfhydryl reagent DTNB (2,2'
      dithiobis(5-nitrobenzoic acid)) in intact microsomes further supports the
      cytosolic localization of this portion of the polypeptide chain. The role of two
      other potential membrane-spanning/associated segments in the C-terminal half of
      the polypeptide chain was examined by investigating the association of the
      protein to the membrane after trypsin cleavage at lysine-41. Activity
      measurements and Western blot analysis after washing with high concentrations of
      salt, as well as after phase separation in Triton X-114, indicate that this
      portion of the protein also binds to the membrane. It is also shown that cleavage
      of the purified protein at Lys-41 and subsequent separation of the fragments
      obtained yields a functional C-terminal polypeptide with the expected length for
      the product encompassing positions 42-154. The location of the active site of
      microsomal glutathione transferase was investigated using radiolabelled
      glutathione together with a second substrate. Since isolated rat liver microsomes
      do not take up glutathione or release the glutathione conjugate into the lumen,
      it can be concluded that the active site of rat liver microsomal glutathione
      transferase faces the cytosolic side of the endoplasmic reticulum.

PMID- 8142473
TI  - Structure and function of glutathione S-transferases.

PMID- 8142474
TI  - beta-Lactoglobulin binding properties during its folding changes studied by
      fluorescence spectroscopy.
AB  - The milk protein, beta-lactoglobulin (BLG) exhibits structural and binding
      properties which vary widely, depending on the medium. These properties of BLG
      are reflected in fluorescence intensities, steady-state anisotropies and phase
      lifetimes of BLG tryptophan residues and of retinol and diphenyl hexatriene (DPH)
      bound to BLG, as functions of pH, ethanol concentration and protein modifications
      (22% ethylated, 90% methylated and 85% acetylated BLGs). Tryptophan quenching
      experiments show that retinol and DPH bind to BLG in 1:1 molar ratios with
      apparent dissociation constants around 10(-7) - 10(-8) M. The strength of retinol
      binding is pH-dependent in the range 3-8, whereas that of DPH binding is not. Two
      different binding sites for these two ligands coexist on the protein. Modified
      BLGs exhibit higher affinities for DPH than the unmodified protein. At all pH
      values investigated, the fluorescence emission at 480 nm of retinol/BLG mixtures
      and retinol, DPH and tryptophan anisotropies and lifetimes change dramatically
      with midpoint at 27% ethanol for the first parameter and 35% for the others,
      suggesting simultaneous beta-strand to alpha-helix transition and the
      dissociation of BLG complexes at 35% ethanol. An intermediate state, possibly
      'molten globular', occurs around 20% ethanol, as deduced from anisotropy and
      lifetime measurements.

PMID- 8142475
TI  - Recombinant rat nucleoside diphosphate kinase isoforms (alpha and beta):
      purification, properties and application to immunological detection of native
      isoforms in rat tissues.
AB  - We previously demonstrated that at least two isoforms of nucleoside diphosphate
      (NDP) kinase, the products of two different tandemly arrayed genes, are present
      in rat. To understand the physiological role of each isoform, some biochemical
      properties of recombinant rat NDP kinase alpha- and beta-isoforms, produced in
      large amount, were studied. cDNAs of the two isoforms were inserted in an
      expression vector pET3b and recombinant enzymes were overproduced in Escherichia
      coli. Their primary structures were different from the native enzymes in that the
      latter suffer from modification of the NH2-terminal end. The two recombinant
      isoforms were purified from the cell lysate to apparent homogeneity by ammonium
      sulfate fractionation followed by three successive column chromatographies.
      Despite their extreme similarity in the amino-acid sequences, the two showed
      somewhat different enzymic properties in terms of di- and triphosphate nucleotide
      substrate specificity. They showed similar mobilities on SDS-PAGE as expected
      from their calculated molecular weight (alpha-isoform, 17,283 versus beta
      isoform, 17,192) but differed in isoelectric point (alpha-isoform, pI 6.7; beta
      isoform, pI 7.8) and heat stability. Polyclonal antibody which reacted with both
      isoforms and alpha-isoform-specific monoclonal antibodies differentially
      recognized native enzymes from rat tissues after the tissue extracts were
      separated by isoelectric focusing gel electrophoresis under a denaturation
      condition. The results showed that the alpha-isoform, though its amount varied
      from one tissue to another, was the major form in rat tissues examined compared
      with the beta-isoform which was detectable in brain and testis. There was no
      preference in their subcellular localization when examined with myelin,
      synaptosomal supernatant and total homogenate fractions from the rat cerebrum and
      cerebellum.

PMID- 8142476
TI  - Amino-acid sequence of the cytochrome c3 (M(r) 26,000) from Desulfovibrio
      desulfuricans Norway and a comparison with those of the other polyhemic
      cytochromes from Desulfovibrio.
AB  - The amino-acid sequence of an octaheme cytochrome c3 isolated from Desulfovibrio
      desulfuricans Norway is presented. The protein molecule (M(r) 26,000) comprises
      two identical subunits of 111 amino acids with the characteristics typical of
      tetrahemic cytochrome c3 class. Comparisons between the amino-acid sequences and
      physiological properties of cytochrome c3 (M(r) 26,000) and cytochromes c3 (M(r)
      13,000) isolated from various species of Desulfovibrio showed the existence of
      considerable differences. In order to distinguish between the various subclasses
      in the cytochrome c3 superfamily, the amino-acid sequence of cytochrome c3 (M(r)
      26,000) was compared with six known cytochrome c3 (M(r) 13,000) sequences as well
      as with the sequence of the four c3-like domains of a high molecular weight
      cytochrome c (Hmc) containing 16 hemes per molecule of 65,500 Da, isolated from
      Desulfovibrio vulgaris Hildenborough. The evolution and phylogenetic
      relationships of these various polyhemic cytochromes are discussed.

PMID- 8142477
TI  - Immune complex independent activation of complement, C1s secreted from hamster
      embryo malignant fibroblasts, Nil2C2 in serum free culture medium.
AB  - Antibody independent activation of complement C1s was examined by immunoblot
      analysis using an antibody against a synthetic peptide of hamster C1s L chain.
      Approx. 50% of C1s secreted from hamster embryo malignant fibroblasts Nil2C2 was
      functionally active in its two-chain form in the serum free culture medium. In
      contrast, no active C1s was found in a culture medium of hamster embryo
      fibroblasts (HEF). Active C1s was detectable, however, in the culture medium
      after HEF became a cell line. The immune complex independent activation of C1s
      was also observed in rat cell lines but not in secondary rat embryo fibroblasts.
      C1s in a membrane fraction of Nil2C2 was a proenzyme form and was not activated
      by incubation of the membrane itself suggesting that C1s was activated after
      secretion. The activation of C1s was not inhibited by human C1 inhibitor (C1
      INH), benzamidine or soy bean trypsin inhibitor (SBTI) but was inhibited by
      leupeptin, nitrophenyl guanidinobenzoate and DFP. Our results suggest that C1s is
      activated either by a serine proteinase(s) other than those reported to cleave
      C1s or by an activator which directly stimulates autoactivation of C1s.

PMID- 8142478
TI  - Arg-188 and Trp-144 are implicated in the binding of urea and acetamide to the
      active site of the amidase from Pseudomonas aeruginosa.
AB  - Urea is a time-dependent active-site-directed inhibitor of Pseudomonas aeruginosa
      amidase. We found that 20 mM hydroxylamine caused bound urea to be released from
      the inactive urea:amidase complex with the restoration of enzyme activity. Bound
      urea restricts the titrability of the enzyme's -SH groups to 6 per hexameric
      molecule and protects it against thermal denaturation suggesting that urea
      binding provokes a conformational change in the enzyme. Mutations in the P.
      aeruginosa amidase gene that reduce the binding affinity of the enzyme for both
      urea and the substrate acetamide have been identified by direct sequencing of PCR
      amplified mutant genes and confirmed by sequencing cloned PCR-amplified genes.
      The mutations were in two regions of the enzyme substituting either Arg-188 (or
      Gln-190, in one case) or Trp-144; one amidase that bound neither urea nor
      acetamide was doubly mutant with an amino-acid change at both sites.

PMID- 8142479
TI  - Identification of tyrosine as a functional residue in the active site of
      Escherichia coli dUTPase.
AB  - dUTP nucleotidohydrolase (dUTPase, EC 3.6.1.23) from E. coli contains a total of
      six tyrosine residues per trimer. About half of them were found to be susceptible
      to acetylation with N-acetylimidazole or to nitration with tetranitromethane with
      concomitant loss of activity. Deacetylation with N-hydroxylamine leads to full
      reactivation. Inhibitory products of dUTP hydrolysis, i.e., dUMP and inorganic
      pyrophosphate together with the cofactor Mg2+ protect significantly against
      inactivation and chemical modification. In the Cu(2+)-dUTPase complex, charge
      transfer from Cu2+ to the tyrosinate anion was perturbed by the presence of the
      substrate dUTP. These results, together with the occurrence of one tyrosine
      residue in a strictly conserved sequence motif suggest the critical importance of
      this residue for the function of the enzyme.

PMID- 8142480
TI  - Characterization of the surfactin synthetase multi-enzyme complex.
AB  - Three subunits (srfAORF1, srfAORF2 and srfAORF3) of the Bacillus subtilis
      surfactin synthetase multi-enzyme complex have been identified by SDS-PAGE and
      Western blot analyses. In accordance with the sequence analysis of the surfactin
      (srfA) operon, the protein subunits have a molecular mass of 402,000 Da, 401,000
      Da and 144,000 Da, respectively. Confirmation of the identity of the proteins was
      obtained by analysing the total protein content of a number of mutant strains
      which harbour deletions or insertions either in the srfA promoter or in different
      positions within the srfA operon. The three subunits were partially purified by
      means of a series of chromatographic steps including ion-exchange chromatography,
      hydrophobic chromatography and gel filtration chromatography. The partially
      purified proteins were used in activity assays to establish their amino-acid
      recognition specificity. In agreement with previously published results, this
      analysis showed that srfAORF1 recognizes glutamic acid and Leu, srfAORF2
      recognizes Val, aspartic acid and Leu and srfAORF3 recognizes Leu. In addition,
      the subunits can activate and bind other amino acids, although with lower
      specificity. In particular, srfAORF1 binds Val, Ile and aspartic acid, srfAORF2
      glutamic acid and Ile and srfAORF3 Ile and Val. Competition experiments as well
      as sequence comparison strongly suggest that the Leu binding sites of the three
      subunits can accept, beside Leu, Ile and Val. The kinetic parameters of srfAORF3
      for Leu, Ile and Val have been determined.

PMID- 8142482
TI  - Substrate characterization of the Saccharomyces cerevisiae protein
      farnesyltransferase and type-I protein geranylgeranyltransferase.
AB  - The in vitro substrate preferences of recombinant S. cerevisiae protein
      farnesyltransferase and type-I protein geranylgeranyl-transferase were
      determined. Proteins ending in 16 different CaaX sequences (C = cysteine, a =
      aliphatic amino acid, X = variable amino acids) were used to determine the
      protein substrate preferences of these S. cerevisiae prenyltransferases. The
      identities of the attached prenyl groups were confirmed by iodomethane treatment
      of prenylated substrates and reverse-phase HPLC. The CaaX preference of each
      recombinant yeast enzyme was found to be nearly identical to the reported
      preferences of purified mammalian protein farnesyltransferase and type-I protein
      geranylgeranyltransferase. S. cerevisiae farnesyltransferase preferentially
      farnesylated CaaX sequences ending in methionine, cysteine or serine. The
      farnesyltransferase also attached geranylgeranyl to some CaaX sequences ending in
      methionine, leucine and cysteine. The S. cerevisiae type-I
      geranylgeranyltransferase preferentially geranylgeranylated CaaX sequences ending
      in leucine and to a lesser degree methionine. Yeast extracts were found to
      contain prenylating activities identical to those observed with the recombinant
      enzymes. Farnesyltransferase activity in yeast extracts exceeded type-I
      geranylgeranyltransferase activity by at least 3-fold, resulting in prenylation
      of leucine-ending CaaX substrates with a mixture of 75% geranylgeranyl and 25%
      farnesyl. These results suggest that some substrate overlap may occur between the
      S. cerevisiae protein farnesyltransferase and the type-I protein
      geranylgeranyltransferase in vivo.

PMID- 8142481
TI  - A glutathione S-transferase (GST) isozyme from broccoli with significant sequence
      homology to the mammalian theta-class of GSTs.
AB  - A novel glutathione S-transferase (GST) was purified from broccoli (Brassica
      oleracea var. italica). Partial amino-acid sequencing indicated that the protein
      shared significant homology with several different plant GSTs from maize, silene,
      Dianthus, Nicotiana and Triticum, but little homology to yeast (Issatchenkia)
      GST. One region of the polypeptide near the N-terminal also shared significant
      homology to a region of rat 5-5, rat 12-12 and human theta-GST (collectively
      referred to as the theta-GST-class) but little structural homology to the common
      mammalian cytosolic GSTs (alpha-, mu- or pi-classes). The broccoli GST was
      retained on a novel membrane based glutathione affinity matrix and displayed
      activity towards 1-chloro-2,4-dinitro-benzene (CDNB), a general GST substrate, as
      well as 4-nitrophenethyl bromide, a marker substrate for the theta-class of GSTs.
      The characteristics of the broccoli GST potentially define it as a member of the
      theta-class. This is consistent with the view that the theta-class may have
      arisen prior to the divergence of animals and plants while the mammalian mu-, pi-
      and alpha-classes evolved after the two kingdoms were established.

PMID- 8142483
TI  - Phosphorylation of human preprogastrin 93-101 by a Golgi membrane kinase from rat
      mammary gland.
AB  - The precursor of the acid-stimulating hormone gastrin contains a phosphorylation
      site which is immediately adjacent to a functionally important cleavage site, and
      which occurs in a sequence resembling the phosphorylation sites in casein. We
      have examined phosphorylation of human preprogastrin 93-101 with [gamma-32P]ATP
      by a Triton-solubilized Golgi membrane preparation from mammary glands of
      lactating rats. The activity of solubilized Golgi membranes was approx. an order
      of magnitude greater than that of intact vesicles suggesting a luminal
      orientation of the kinase. Incorporation of 32P was linear for up to 12 min at 30
      degrees C, and the half-maximal rate of phosphorylation at 1 mM ATP was observed
      at peptide concentrations of 0.2 mM. The Km for ATP was 0.12 mM and the maximal
      velocity was 2.17 nmol of peptide per min per mg Golgi protein. Proteinase
      inhibitors (leupeptin, pepstatin, benzamidine) and p-nitrophenyl phosphate did
      not influence phosphorylation. The incorporation of 32P was inhibited by poly-L
      lysine but not by heparin. We conclude that the phosphorylation site in
      progastrin is a substrate for a Golgi membrane kinase and that a similar enzyme
      might act on endogenous progastrin in vivo.

PMID- 8142484
TI  - Selective modification of putative uridine-binding site of uridine phosphorylase
      from E. coli with fluorescein 5'-isothiocyanate.
AB  - A putative uridine-binding site of uridine phosphorylase (EC 2.4.2.3) from E.
      coli was modified with fluorescein 5'-isothiocyanate (FITC). Treatment with FITC
      irreversibly inactivates the enzyme (Ki = 1.0 mM, k2 = 0.15 min-1). Under the
      conditions of 90% inactivation the incorporation of the reagent reaches about 1
      mol per mol of the enzyme subunit. Addition of uridine prevents the enzyme
      inactivation by FITC. In contrast to this, addition of a second substrate
      phosphate increases the rate of inactivation by 2.3-fold (k2 = 0.34 min-1), but
      has no effect on the affinity of the reagent to the enzyme. The modified protein
      retains the ability to bind phosphate but not uridine. According to differential
      absorption spectroscopy data, the binding of phosphate to the active site of the
      enzyme is accompanied by conformational changes which may accelerate the
      inactivation rate. The data presented suggest that in the UPase FITC occupies the
      putative uridine-binding site, while the phosphate-binding site still retains the
      ability to interact with the second substrate.

PMID- 8142485
TI  - Fourier transform infrared spectroscopy and differential scanning calorimetry of
      transferrins: human serum transferrin, rabbit serum transferrin and human
      lactoferrin.
AB  - Fourier transform infrared spectroscopy (FTIR) and differential scanning
      calorimetry (DSC) have been used to investigate the solution structure and
      thermal stability of human serum transferrin (HST), human lactoferrin (HLF) and
      rabbit serum transferrin (RST) in their diferric and apo forms. Our study shows
      that: (A) The secondary structure of all the proteins studied (estimated in H2O)
      was in the range 43-53% alpha-helix and 23-28% beta-sheet. These values differ
      markedly from previously reported circular dichroism (CD) data. This is
      attributed to the fact that FTIR and CD measure different aspects of secondary
      structure (hydrogen bonding and dihedral angles, respectively). (B) The secondary
      structural content of the proteins is not altered by iron binding or release.
      However, the iron-free proteins undergo a greater extent of 1H-2H exchange than
      the diferric proteins indicating that significant structural changes do occur
      upon iron binding/release. (C) The removal of iron leads to thermal
      destabilization of HST, HLF and RST. Structural variation in the apo transferrins
      is indicated by the observation of a single irreversible DSC transition for apo
      human lactoferrin, a double DSC transition for apo human serum transferrin (one
      reversible) and a broad irreversible asymmetric DSC transition for apo rabbit
      serum transferrin. FTIR spectroscopy shows that a distinct loss of protein
      secondary structure occurs at the transition temperatures shown by DSC.

PMID- 8142486
TI  - Sulfate- and sialic acid-containing glycolipids inhibit DNA polymerase alpha
      activity.
AB  - The effects of various glycolipids on the activity of immunoaffinity-purified
      calf thymus DNA polymerase alpha were studied in vitro. Preincubation with sialic
      acid-containing glycolipids, such as sialosylparagloboside (SPG), GM3, GM1, and
      GD1a, and sulfatide (cerebroside sulfate ester, CSE) dose-dependently inhibited
      the activity of DNA polymerase alpha, while other glycolipids, as well as free
      sphingosine and ceramide did not. About 50% inhibition was achieved by
      preincubating the enzyme with 2.5 microM of CSE, 50 microM of SPG or GM3, and 80
      microM of GM1. Inhibition was noncompetitive with both the DNA template and the
      substrate dTTP, as well as with the other dNTPs. Since the inhibition was largely
      reversed by the addition of 0.05% Nonidet P40, these glycolipids may interact
      with the hydrophobic region of the enzyme protein. Apparently, the sulfate moiety
      in CSE and the sialic acid moiety in gangliosides were essential for the
      inhibition since neither neutral glycolipids (i.e., glucosylceramide,
      galactosylceramide, lactosylceramide) nor asialo-gangliosides (GA1 and GA2)
      showed any inhibitory effect. Furthermore, the ceramide backbone was also found
      to be necessary for maximal inhibition since the inhibition was largely abolished
      by substituting the lipid backbone with cholesterol. Increasing the number of
      sialic acid moieties per molecule further enhanced the inhibition, while
      elongating the sugar chain diminished it. It was clearly shown that the N-acetyl
      residue of the sialic acid moiety is particularly essential for inhibition by
      both SPG and GM3 because the loss of this residue or substitution with a glycolyl
      residue completely negated their inhibitory effect on DNA polymerase alpha
      activity.

PMID- 8142487
TI  - Bile acid glucuronidation by rat liver microsomes and cDNA-expressed UDP
      glucuronosyltransferases.
AB  - Four rat UDP-glucuronosyltransferases (UGTs), UGT2B1, UGT2B2, UGT2B3 and UGT2B6,
      synthesized in COS-7 cells from appropriate cDNA clones were screened for
      activity towards a range of bile acids, neutral steroids and retinoic acid. For
      comparison, as well as optimization of enzymatic assays and product
      identification, rat liver microsomal preparations from Sprague-Dawley, Fischer
      344 and phenobarbital-induced Fischer 344 male rats were also used as enzyme
      sources. Only two of the expressed proteins, UGT2B1 and UGT2B2, were active in
      bile acid glucuronidation. UGT2B1 exhibited a high substrate specificity for the
      carboxyl function of bile acids, whereas UGT2B2 demonstrated less specificity,
      accepting both hydroxyl and carboxyl functions of bile acids. The preferred
      substrates for both cloned enzymes were mono-hydroxylated bile acids, followed by
      di-hydroxylated 6-OH compounds. The levels of UGT activity were sufficient to
      allow for the identification of the biosynthesized products. The data presented
      here demonstrate that bile acid glucuronidation is carried out, at least in part,
      by members of the UGT2B subfamily. Similar results have been obtained previously
      for neutral steroid glucuronidation. UGT2B3 and UGT2B6 was not involved in BA
      glucuronidation; none of the cloned enzymes was active toward retinoic acid.

PMID- 8142488
TI  - The activity of S-thiomethyl modified creatine kinase is due to the regeneration
      of free thiol at the active site.
AB  - Creatine kinase modified by S-methyl methanethiosulfonate and devoid of reactive
      thiol group has been reported to retain about 18-40% of the activity of the
      native enzyme. It has now been found that during the reaction catalyzed by the
      modified enzyme the rate increases with time and if the reaction is allowed to
      continue sufficiently long, the enzyme eventually recovers full activity. The
      presence of substrates is not required for the reactivation as suitable dilution
      after removal of MMTS in excess leads to complete reactivation of the MMTS
      modified enzyme with the simultaneous regeneration of reactive thiol per each
      dimeric molecule as shown by determinations with DTNB and IAN. The addition of
      MMTS during the course of reactivation again inactivates the reactivated enzyme.
      The activity recovery is therefore due to the regeneration of reactive thiol and
      it appears that the active-site thiols are essential for the activity of rabbit
      muscle creatine kinase.

PMID- 8142489
TI  - Probing the microenvironments of tryptophan residues in the monomeric crystallins
      of the bovine lens.
AB  - Tryptophan microenvironments have been examined in bovine beta s-, gamma II-,
      gamma IIIa-, gamma IIIb-, gamma IVa- and gamma IVb-crystallins by fluorescence
      methods. The proteins could be divided into two groups on the basis of the
      accessibilities of their tryptophan residues. The first group, comprising beta s,
      gamma II and gamma IIIb, appeared to have a compact structure with none of the
      tryptophans accessible to KI and only moderately so to acrylamide. By contrast in
      gamma IIIa, gamma IVa and gamma Vb, all tryptophans were readily accessible to
      acrylamide and 70% of the fluorescence could be quenched with KI. Spectral
      analysis, before and after quenching, time-resolved spectroscopy and simulations
      of the quenching curves suggested that gamma IIIa, gamma IVa and gamma IVb
      contain two classes of tryptophan residues. One class (tau 0 = 0.52 ns, fa = 0.3,
      lambda max = 324 nm) which was completely inaccessible to KI and relatively
      inaccessible to acrylamide (Ksv = 0.25 M-1), was assigned to the topologically
      equivalent residues in positions 42 and 131. The other class (tau 0 = 2.1-3.4 ns,
      fa = 0.7, lambda max = 330 nm) was accessible to both quenchers (Ksv = 5.00-5.15
      M-1 and 2.47-2.60 M-1, for acrylamide and KI, respectively) and corresponded to
      the tryptophan residues in positions 68 and 157. The same classes may be present
      in the other low molecular weight proteins (tau 0 = 0.47-0.55 and 1.55-1.74) but
      the lower emission and low accessibilities to quenchers prevented their
      distinction and suggested that these proteins had more compact structures.

PMID- 8142490
TI  - Conformational change of skeletal muscle alpha-actinin induced by salt.
AB  - We examined the effect of KCl concentration on conformation of skeletal muscle
      alpha-actinin. One-dimensional peptide maps of alpha-actinin digested with
      chymotrypsin indicated that alpha-actinin can take on at least three different
      conformations depending on the KCl concentration of the solvent, i.e., at low (0
      0.02 M KCl), intermediate (0.05-0.2 M KCl), and high (0.3-0.6 M KCl) salt
      concentration. Viscosity measurement and gel-filtration chromatography of alpha
      actinin at these three salt ranges indicated that the axial ratio of alpha
      actinin increased as the ionic strength of the solvent decreased. By assuming 45%
      hydration of the alpha-actinin molecule and using a molecular weight of 210,000,
      dimensions of alpha-actinin were calculated from viscosity data. The size
      estimated under the low-salt conditions was 3.2 x 74.2 nm. They were 3.4 x 51.3
      nm and 4.5 x 40.1 nm, respectively, in the intermediate and high salt ranges. The
      result of the gel-filtration chromatography showed that the conformational change
      was reversible and that the change took place through the elongation and/or
      shortening of the rod domain of the molecule. We explain the salt-induced length
      change of alpha-actinin by the twisted-coiling model proposed by McGough and
      Josephs for erythrocyte spectrin (McGough, A. and Josephs, R. (1990) Proc. Natl.
      Acad. Sci. USA 87, 5208-5212). Pelleting experiments indicated that the
      conformational change affected the binding ratio between alpha-actinin and actin.

PMID- 8142491
TI  - Schools of basic health sciences and medicine merge.

PMID- 8142492
TI  - Physicians fill void in health care system.

PMID- 8142494
TI  - Different wars, same hardships.

PMID- 8142493
TI  - Acute hepatitis with use of over-the-counter herbal remedies.

PMID- 8142495
TI  - Different wars, same hardships.

PMID- 8142496
TI  - Oath-sayers.

PMID- 8142497
TI  - Returning the practice of medicine to physicians.

PMID- 8142498
TI  - The way things were--a reminder.

PMID- 8142499
TI  - [Is it possible to treat infections with non-antimicrobial agents?].

PMID- 8142500
TI  - [Diagnosis of disseminated candidiasis. Overcoming a challenge].

PMID- 8142501
TI  - [Community-acquired pneumonia: prospective study of 101 adult, immunocompetent
      patients for 1 year].
AB  - BACKGROUND: A one year prospective study was carried out to assess the etiology
      of community-acquired pneumonia (CAP), and also to know the incidence,
      characteristics and evolution of infection by Chlamydia pneumoniae; and the
      effectiveness of DNA probes in CAP due to Mycoplasma pneumoniae and Legionella.
      METHODS: One hundred and ten patients with a diagnosis of CAP in the emergency
      department were studied. Serologic studies were performed, and also tests
      commonly used for the diagnosis of respiratory tract pathogens in respiratory
      samples, including serology and culture of Chlamydia pneumoniae and DNA probes
      for Mycoplasma pneumoniae and Legionella. RESULTS: In 72 cases (71.3%) some
      pathogen was found and in 5 cases more than one microorganism was involved. The
      etiology was bacterial in 31% of the cases, with S. pneumoniae being the most
      frequent (19 cases). Forty percent of the cases were "atypical" pneumonias with
      33 cases of M. pneumoniae and 5 by Chlamydia pneumoniae. Diagnostic data of viral
      pneumonia were found in 2 cases. DNA probes were not useful for the diagnosis of
      pneumonia by Legionella pneumophila and had low effectiveness (31.8%) in
      Mycoplasma pneumoniae CAP. CONCLUSIONS: a) M. pneumoniae was the most frequent
      pathogen (33%). b) DNA probes for M. pneumoniae had low sensitivity in sputum
      (31.8%) and none in pharyngeal exudate. c) Acute infection by C. pneumoniae was
      diagnosed in 5 cases. Previous data of infection were recorded in 60.4% of the
      patients. d) Bacterial pneumonia (31%) was underestimated due to a low rate of
      bacteremic cases (7.9%) and the low number of positive cultures with definitive
      diagnostic value. e) The evolution was good except in two cases (death due to
      staphylococcal pneumonia with alcohol withdrawal syndrome and multiorganic
      failure by disseminated chicken-pox).

PMID- 8142502
TI  - [Interobserver agreement in reading tuberculin tests].
AB  - BACKGROUND: The aim of the study was to evaluate the variability between four
      observers in the reading of the tuberculin test (TT). METHODS: The study was
      carried out in the Centro de Salud Mendiguchia Carriche (Madrid) 72 subjects. By
      direct inspection, four observers read tuberculin determination (skin induration)
      independently in each subject. To assess variability, the kappa index (K) was
      calculated. RESULTS: On considering the variable as a dichotomous one, with a cut
      off point of 5 mm was 0.88; and of 10 mm, 0.78. Upon considering the index as
      qualitative in four categories the kappa index in 0 mm was 0.89; in 1-4 mm, 0.24;
      in 5-9 mm, 0.40 and greater than 9 mm, 0.79. In eight of the subjects studied,
      the variability observed in reading the test had conditioned further different
      clinico-epidemiologic attitudes. CONCLUSIONS: The degree of concordance when
      reading TT is significantly lower at the 1-4 mm and 5-9 mm intervals.

PMID- 8142503
TI  - [Endocarditis caused by non-diphtheriae Corynebacterium. Presentation of 12 cases
      and review].
AB  - BACKGROUND: Corynebacterium is known as a pathogen for man, particularly C.
      diphtheriae, while other species may cause disease and particularly cardiac valve
      infection, mainly in immunosuppressed patients, intravenous drug addicts, valve
      prosthesis carriers, patients with previous valvular disease, with congenital
      heart diseases or those submitted to cardiothoracic surgery. METHODS: Seven
      episodes of endocarditis due to Corynebacterium no diphtheriae among six patients
      admitted to our hospital between 1989 and 1992 are analyzed. RESULTS: The mitral
      valve was often affected with a predominance of incidence in the native valve.
      Four cases were cured with antibiotic therapy and in three patients surgical
      valve replacement was required. Recurrence of endocarditis was observed in one of
      the patients. One case of mycotic cerebral aneurysm and one intracranial
      hemorrhage are complications of note. One of the patients had undergone kidney
      transplantation being the first case described with endocarditis by C. no
      diphtheriae in this subset of patients. Transesophageal echocardiography was the
      principal diagnostic measure. CONCLUSIONS: The increase in the number of
      immunosuppressed patients (organ transplantations and acquired immunodeficiency
      syndrome) and prosthesis carriers wake advisable that these microorganisms be
      taken into account as etiologic agents of infectious endocarditis.

PMID- 8142505
TI  - [Multiple antibiotic resistance in Haemophilus influenzae related to serogroup
      B].
AB  - AIM: To study the association between multiply antibiotic resistance in
      Haemophilus influenzae and H. influenzae type B, and to describe levels and
      patterns of antibiotic resistance. METHODS: Statistical analysis and
      susceptibility of 231 H. influenzae strains (52 type B and 179 non-typable )
      isolated consecutively from pediatric patients. RESULTS: Resistance levels for
      type B and non-typable strains were: Ampicillin, 55.3% vs 28.8%; Chloramphenicol,
      44.7% vs 9.2%; Ampicillin plus chloramphenicol, 40.4% vs 7.6%; cotrimoxazole,
      89.3% vs 67.4%; resistance to six or more antibiotics, 36.0% vs 3.8%. CONCLUSION:
      Multiply antibiotic resistance in H. influenzae is strongly associated with type
      B strains, with age of 4 or younger, and with isolation from CSF or blood.
      Resistance is sustained over long periods of time.

PMID- 8142504
TI  - [Comparative activity of several antibiotics against Toxoplasma gondii in a mouse
      model].
AB  - BACKGROUND: Infections with Toxoplasma gondii poses a great hazard to
      immunocompromised patients and to pregnant women. Currently, the recommended
      therapy for toxoplasmosis is the synergistic combination of pyrimethamine and
      sulfadiazine (P/S). However, this therapeutic regimen may be toxic or only
      partially effective. Because pyrimethamine is potentially teratogenic, its use
      during the early months of pregnancy is not recommended. There is a critical need
      for newer and safer compounds for the treatment of toxoplasmosis. These
      considerations led us to evaluate other potential therapeutic agents-
      minocycline, clindamycin, roxithromycin, azithromycin, clarithromycin and
      miocamycin--as well as comparison of P/S and spiramycin efficacy against T.
      gondii. METHODS: The activity of antibiotics was tested in a murine model of
      acute toxoplasmosis. NMRI mice were infected intraperitoneally with 200
      tachyzoites of the highly virulent RH strain of T. gondii, and treated, every 12
      h or 24 h, for ten consecutive days. RESULTS: P/S (a dose of 4/250 mg/kg of body
      weight per day), minocycline (200 mg/kg) and azithromycin (200 mg/kg) were the
      most active compounds (100% of mice survival). Clindamycin, roxithromycin,
      spiramycin and clarithromycin were less effective. Miocamycin was not effective
      in this model. CONCLUSIONS: Our findings support the view that minocycline and
      azithromycin could be useful in many cases of toxoplasmosis. Clinical studies are
      needed to determinate the relative efficacy and safety of these antibiotics for
      the treatment of toxoplasmosis in humans.

PMID- 8142506
TI  - [Visceral leishmaniasis and multiple organ failure].
AB  - BACKGROUND: Visceral leishmaniasis is a parasitic disease which has a good
      prognosis in previously healthy patients who have been successfully treated. At
      present, visceral leishmaniasis is increasingly reported in immunocompromised
      patients including those with AIDS, whose display a fulminating form and higher
      mortality. We report a case of visceral leishmaniasis in a healthy patient with a
      non classical clinical evolution of the disease. METHODS: A 17 years old patient
      without immunosuppressive factors was diagnosed by histologic evaluation of bone
      marrow which revealed intracellular leishmania amastigotes. Immediately the
      patient received treatment with antimony therapy. RESULTS: Patient developed a
      multi-organic failure (respiratory distress, disseminated intravascular
      coagulation, hepatic and renal insufficiency) and died at 13 days his after
      intensive care unit admission. CONCLUSIONS: The major new finding of this study
      is that in normal humans visceral leishmaniasis can have a dramatic short-term
      follow up in spite of correctly treatment. We suggest a possible immunological
      mechanism similar at non septic pathology.

PMID- 8142507
TI  - [Escherichia vulneris infection. Report of 2 cases].
AB  - BACKGROUND: Escherichia vulneris is an enterobacteriaceae seldom isolated in
      microbiology laboratories. We report two cases of infection with positive
      cultures for this microorganism. METHODS: Microbiological cultures of wound
      secretion and peritoneal fluid on usual media. Identification by PASCO and API
      20E systems. Antimicrobial sensitivity was performed by a commercial
      microdilution system. RESULTS: The first case is a postsurgical hand infection
      from which was isolated Escherichia vulneris with Enterococcus faecium, it shows
      the typical presentation of infection by this bacteria. The second case consists
      of a peritonitis after aggressive abdominal surgery. In the peritoneal fluid
      culture, Escherichia vulneris and Cedecea neteri were recovered. CONCLUSIONS: The
      isolation of Escherichia vulneris has not been reported previously in Spain. We
      contribute towards its better knowledge with two clinical reports: a typical
      infection and an exceptional isolation from peritoneal fluid.

PMID- 8142508
TI  - [The genus Mobiluncus and its clinical significance].

PMID- 8142509
TI  - [Indolent cutaneous ulcer in a patient with HIV infection].

PMID- 8142510
TI  - [Discovery of a mycelial fungus in a blood culture (Bactec NR-860) from a patient
      with an implantable reservoir].

PMID- 8142511
TI  - [Miliary tuberculosis after intravesical Bacillus Calmette-Guerin
      administration].

PMID- 8142512
TI  - [Neisseria meningitidis and pneumonia: another case].

PMID- 8142513
TI  - [Purulent pneumococcal pericarditis].

PMID- 8142514
TI  - [Endocarditis caused by Streptococcus equisimilis affecting a prosthetic valve].

PMID- 8142515
TI  - [Acute mastitis caused by Salmonella sp. during pregnancy].

PMID- 8142516
TI  - [Diagnostic imaging in Lemierre syndrome].

PMID- 8142517
TI  - [Bullous erythema multiforme caused by human parvovirus B19].

PMID- 8142518
TI  - [Pyogenic liver abscess and HIV].

PMID- 8142519
TI  - Efficient diagnosis of Pneumocystis carinii pneumonia.
AB  - In patients with HIV infection the diagnosis of PCP is relatively simple when
      patients present late, with advanced pneumonia. The diagnosis becomes more
      difficult when patients present with minimal symptoms, are receiving specific
      prophylactic therapy or have had previous AIDS-related pulmonary diseases. A
      number of non-invasive tests, such as Gallium scanning, exercise-induced
      hypoxaemia, DTPA scanning and lung function testing have been developed to
      improve on the diagnostic value of clinical examination and the chest X-ray.
      Although each has its own particular advantages and disadvantages, the most
      efficient means of diagnosing PCP, in patients presenting with respiratory
      symptoms, is to use these investigations as part of a diagnostic algorithm,
      thereby maximizing resources and defining relative risks for different types of
      patients.

PMID- 8142520
TI  - A brighter image for genitourinary medicine clinics.

PMID- 8142521
TI  - HIV/AIDS, advocacy and anti-discrimination legislation--the Australian response.
AB  - This paper will address the role of mass communication strategies in the
      reduction of HIV/AIDS discrimination in Australia. It will focus on the
      interdependence of mass communication and legislation in health promotion
      campaigns with particular reference to the Disability Discrimination Act 1992.
      This will be discussed in the context of other HIV/AIDS strategies in Australia.
      The public health impact of discrimination is explored in relation to HIV/AIDS
      and the role of anti-discrimination legislation is discussed. Public health
      legislation can serve as a symbolic reflection of public opinion or actively
      change it. Laws can transform the practices of both public and private
      institutions and thus decrease discrimination. They can also provide specific
      remedies for people adversely affected by discriminatory attitudes and practices.
      Mass communication can maximize the impact of legislation by promoting awareness
      of new laws and, more importantly, lead changes in the attitudes of the polity
      and the wider public.

PMID- 8142522
TI  - Meatoscopy: an important technique for assessing meatal warts in men.
AB  - A total of 506 meatoscopic examinations showed this is a simple, safe, rapid,
      well-tolerated, useful procedure to assess the extent of warts at the meatus and
      in the distal urethra of men. The procedure was performed in 307 patients. Sixty
      five (52.5%) of 124 men with meatal warts had additional urethral lesions not
      readily treatable. All proximal warts were confined to the fossa navicularis.
      Meatoscopy assisted in immediate rational planning of therapy. In assessing
      patients without meatal warts, lesions in the fossa navicularis were observed in
      4 (6.7%) of 60 men with external penile warts, 4 (7.8%) of 51 men with a history
      of 3 previous episodes of urethritis, and in 8 (23.5%) of 34 men who had been in
      contact with warts. No relation was found between the distribution of warts,
      demographic details of patients, or duration of warts; the effect of previous
      urethritis on development of warts was unclear. It was concluded, following 199
      repeated examinations, that the procedure was not associated with recurrence or
      proximal extension. Only 2 minor adverse events were recorded. Meatoscopy is
      recommended as part of the assessment of men with meatal warts and men who have
      been in contact with warts. The procedure should be considered in patients with
      external warts but no meatal warts, and in patients with a history of 3 previous
      episodes of urethritis over 3 years.

PMID- 8142523
TI  - How should an AIDS diagnosis be given? The views of patients.
AB  - The report aimed at obtaining information about patients' experience of how the
      diagnosis of AIDS was given to them by their doctors, and about patients'
      satisfaction with the consultation. Thirty people with AIDS completed a self
      report questionnaire enquiring about their views and satisfaction with the
      process of communication of the diagnosis. Results showed that about two-thirds
      of patients were satisfied, while almost a quarter were definitely not satisfied
      with the consultation. Satisfaction was associated with the general attitude of
      the person giving the diagnosis and with the quality of the information given.
      The relevance of the findings for the training of doctors is discussed.

PMID- 8142524
TI  - Demonstration of Epstein-Barr virus DNA in acetowhite lesions of the vulva.
AB  - Acetowhite lesions in the vulva disclosing koilocytosis have been related to
      infection by human papilloma virus (HPV). Because of the clinical resemblance of
      these lesions to oral hairy leukoplakia (OHL), and EBV-manifestation, 23 women
      with acetowhite koilocytotic lesions in the vulva were examined. The PCR
      technique was used to detect EBV DNA as well as HPV DNA in 17% of 23 patients
      examined. In a control group of 19 patients EBV DNA was detected in 11% and HPV
      DNA in 42% of cell samples from normal vulvar mucosa. EBV DNA has not previously
      been demonstrated in the vulvar mucosa, and this virus might be related to
      subclinical acetowhite lesions.

PMID- 8142525
TI  - The impact of lubricants on latex condoms during vaginal intercourse.
AB  - The objective was to evaluate the impact of additional lubricant on condom
      breakage and slippage. Two hundred and sixty-eight couples used 6 new and 6 aged
      condoms during vaginal intercourse and were instructed to use 2 of each type with
      either water-based lubricant, oil-based lubricant or no additional lubricant. The
      use of either oil-based or water-based lubricant increased slippage rates of new
      and aged condoms, although only one pairwise comparison (oil-based lubricant vs.
      no additional lubricant) was statistically significant (8.5% vs. 3.8%, P =
      0.004). The use of oil-based lubricant increased breakage, although not
      statistically significantly, in both new and aged condoms. Water-based lubricant
      did not impact the breakage rate of the new condoms and decreased the breakage
      rate of the aged condoms (no additional lubricant 4.5% vs. water-based lubricant
      2.1%, P = 0.029). From a functional perspective, this study suggests that condom
      users should be told not to use oil-based lubricants. The negative impact of
      water-based lubricant on slippage may be outweighted by the protective influence
      on breakage, especially for aged condoms. Over three-quarters of the couples
      (76%) had at least some incorrect knowledge, according to current condom
      instructions, of the type of lubricant that should be used with condoms.

PMID- 8142526
TI  - Heterosexual partnership characteristics of university women.
AB  - In order to assess the individual risk of acquiring sexually transmitted diseases
      (STDs), both characteristics of the partnership and the individual should be
      considered. Partnership characteristics have been used as risk markers for STD
      transmission but their distribution has not been well described. Using a self
      administered questionnaire, we collected information on the partnership
      characteristics of the 4 most recent sexual partners of the members of 9
      university women's social organizations at the University of Michigan.
      Respondents were asked to report the setting of the first meeting of partners,
      the length of the presexual relationship, condom use at the first sexual
      encounter and the total number of sexual encounters within that partnership. We
      graphically analyse changes in these partnership characteristics with respect to
      partnership order. As the number of sexual partners increased the women in this
      population were more likely to report partnership characteristics associated with
      an increased risk of acquiring an STD. In addition, partnership characteristics
      varied with the order of the partnership, implying that no single partnership is
      representative of all others.

PMID- 8142527
TI  - Age-related increase in sexual behaviours and decrease in regular condom use
      among adolescents in Australia.
AB  - The prevalence of sexual behaviours was estimated from a survey of 3854
      Australian secondary school students. Self-reported prevalence of intercourse
      increased from 9.9% (age 13 years or less) to 23.9% (age 15) and 51.2% at age 17
      and over. Among 932 sexually experienced youth in the final 3 years of secondary
      school, 26% of males and 18% of females reported having 3 or more partners in the
      previous year; 89.4% had used a condom at least once, with males (71.8%)
      reporting more last occasion condom use than females (53.4%). 'Last occasion' and
      'usual', but not lifetime, condom use was significantly lower among older
      respondents. Although nearly 90% of females in each of 3 age groups reported
      lifetime condom use, just 27.6% of female students aged 17 or more reported that
      condoms were always used during intercourse. The decline with age, noted in
      research with adults and older adolescents, may begin in the middle teens.

PMID- 8142528
TI  - Human immunodeficiency virus and Treponema pallidum infections in Nigerian
      patients with leprosy.
AB  - Fifty-one patients were selected from 4 leprosaria in eastern Nigeria and were
      examined for evidence of syphilis. They were screened serologically for
      treponemal and human immunodeficiency virus (HIV) infections. Information about
      their sexual behaviour and demographic data were obtained to determine the
      factors associated with increased risk of contracting sexually transmitted
      diseases (STD). They were compared with 115 controls. The results showed that
      positive treponemal tests were more common in those patients living outside the
      leprosaria (P < 0.05). Age and sex of the patients living inside the leprosaria
      were not factors associated with treponemal infections. Leprosy appeared to be a
      factor for T. pallidum infection when compared with the control group (P < 0.05;
      OR 476; CI 1.16, 19.5). One leprosy patient and one control subject had positive
      HIV tests and there was no significant association between leprosy and HIV
      infection. These findings suggest the possibility of the spread of sexually
      transmitted diseases amongst the leprosy patient population. The importance with
      respect to control measures is that leprosy patients living outside leprosaria
      may constitute a potential reservoir for introducing sexually transmitted
      diseases into the leprosaria.

PMID- 8142529
TI  - The determination of amines in the vaginal secretions of women in health and
      disease.
AB  - The presence of amines in vaginal fluid is thought to be an important
      contributory factor in the pathogenesis of bacterial vaginosis (BV). As part of
      on-going work investigating the aetiology of this infection, two separate studies
      were performed in which gas chromatography was used to measure and compare the
      amines present in the vaginal secretions of normal women, a group infected with
      BV and some having other sexually transmitted diseases. The amines studied were
      methylamine, isobutylamine, putrescine, cadaverine and phenylethylamine. The
      results of the studies were contrary to expectations, in that they showed an
      overall similarity in both normal women and in those with BV and other vaginal
      infections. These findings now bring in to question the validity of amines being
      a reliable focus, either in the diagnosis of BV, or in investigations into the
      aetiology of the disease.

PMID- 8142530
TI  - Experience of HIV prevention interventions among female sex workers in Delhi,
      India.
AB  - This paper describes the effect of HIV prevention intervention among female sex
      workers in Delhi. Over a 2-year period we found a marked increase in condom use
      with little increase in HIV seroprevalence. The prevalence of HIV infection did
      not increase during the study period (1 positive among 701 in 1988 vs 1 positive
      in 600 in 1990).

PMID- 8142531
TI  - Recurrent bullous balanitis: an unusual presentation of balanitis xerotica
      obliterans.

PMID- 8142532
TI  - Treatment of AIDS-associated oral hairy leukoplakia with cryotherapy.

PMID- 8142533
TI  - Disseminated aspergillosis in the acquired immunodeficiency syndrome.
AB  - The relationship of disseminated aspergillosis with human immunodeficiency virus
      (HIV) infection is unclear. In the initial case definition of acquired
      immunodeficiency syndrome (AIDS) developed by the Centres for Disease Control
      (CDC), Atlanta, aspergillosis was included as an AIDS-defining opportunistic
      infection. In view of the primary relationship of aspergillosis with neutropenia
      rather than with lymphocyte depletion, as well as the lack of aspergillar
      infections among reported AIDS cases, aspergillosis was later deleted from the
      CDC case definition of AIDS. We describe a case of disseminated aspergillosis in
      a patient with AIDS, with an extensive literature review of the subject.

PMID- 8142534
TI  - Rupial syphilides in a single male.

PMID- 8142535
TI  - An audit of the value of microscopy of gram-stained and wet film preparations for
      the diagnosis of bacterial vaginosis in a department of genitourinary medicine.

PMID- 8142536
TI  - Ulcerative colitis and balanoposthitis.

PMID- 8142537
TI  - The role of aerosol pentamidine prophylaxis.

PMID- 8142538
TI  - Contact tracing of patients with pelvic inflammatory disease.

PMID- 8142539
TI  - Treatment of anorectal manifestations of AIDS: past and present.

PMID- 8142540
TI  - Ovarian follicular growth and development in mammals.
AB  - Evidence from several species indicates that the initial stages of follicular
      growth proceed very slowly. In contrast, the stages after antrum formation are
      much more rapid. Atresia seems to be most prevalent as follicles approach the
      size at which they could be recruited for potential ovulation. Although most
      follicles become atretic around that stage, a few are recruited into a cohort or
      wave of follicles that continue to grow beyond the stage at which atresia
      normally occurs. Next, a species-specific number of follicles is selected for
      dominance. In some species (e.g. rats, primates, pigs), dominant follicles
      develop only during the follicular phase and are thus destined for ovulation. In
      another group of species (e.g. cattle, sheep, horses), recruitment, selection,
      and dominance occur at regular intervals, but only the dominant follicle present
      during the follicular phase ovulates. There is evidence that the mechanism that
      allows some follicles to be recruited for potential dominance/ovulation is a
      small elevation in basal FSH that, by chance, occurs around the time the follicle
      would normally begin atresia. Some recruited follicles are saved from atresia for
      only a short time. Only the dominant follicle(s) selected from among the
      recruited follicles grows to ovulatory or near-ovulatory size. What determines
      which follicle(s) becomes dominant is not known, but dominance appears to be
      maintained by negative feedback effects of products of the dominant follicle on
      circulating FSH. Selection and dominance are accompanied by progressive increases
      in the ability of thecal cells to produce androgen and granulosa cells to
      aromatize androgen to estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142541
TI  - Current status of the hypothesis that mammalian ovulation is comparable to an
      inflammatory reaction.
AB  - This presentation reviews current information on the events that lead to rupture
      of an ovarian follicle. It contains a summary of the morphological changes that
      occur at the apex of a follicle wall during ovulation. Existing information shows
      that the tenacious connective tissue layers of the tunica albuginea and theca
      externa must be weakened before the follicle wall can dissociate and break open
      under the force of a modest intrafollicular pressure. These changes are probably
      dependent on transformation of quiescent thecal fibroblasts into proliferating
      cells in a manner that is characteristic of tissue responses to inflammatory
      reactions. The metabolic factors that initiate transformation of the fibroblasts
      are uncertain, but they are probably generated by gonadotropin-induced changes in
      the theca interna and granulosa of a follicle as these layers begin to luteinize
      during the ovulatory process.

PMID- 8142542
TI  - Luteal function: the estrous cycle and early pregnancy.
AB  - A number of morphological and biochemical changes occur as the cells of the
      recently ovulated follicle luteinize and develop into a functional CL. There are
      two distinct steroidogenic luteal cell types that appear to differentiate from
      thecal and granulosal cells in the follicle. The control of progesterone
      secretion is quite different in the two cell types. Prostaglandin F2 alpha (PGF2
      alpha) is the primary luteolytic hormone in most mammals. PGF2 alpha appears to
      exert its antisteroidogenic actions via activation of the protein kinase C
      system, while its cytotoxic effects appear to be mediated via a dramatic increase
      in intracellular levels of free calcium. The mechanisms involved in maternal
      recognition of pregnancy are very diverse between species and may involve direct
      luteotropic stimulation of the CL, reduced uterine secretion of PGF2 alpha,
      and/or inhibition of actions of PGF2 alpha at the level of the CL.

PMID- 8142543
TI  - Action of a cyclopropenoid fatty acid on the corpus luteum of pregnant and
      nonpregnant ewes.
AB  - The effects of a cyclopropenoid fatty acid on luteal cell function were studied.
      In experiment 1, pregnant ewes were laparotomized on Day 18 of gestation and ewes
      with CL in both ovaries were unilaterally ovariectomized. Either 1.09 mg of an
      extract of Sterculia foetida seeds, containing 750 micrograms sterculic acid
      methyl ester (SA, n = 6), or 1.09 mg oleic acid methyl ester (OA, n = 6) was
      injected into the artery supplying the ovary bearing CL. Jugular blood was
      collected on Day 18 before surgery and daily thereafter until Day 30 of gestation
      or until detection of estrus, whichever occurred first. Serum was assayed for
      progesterone (P4) by RIA. In experiment 2, CL were removed from ewes on Day 10 of
      the estrous cycle and slices of luteal tissue were incubated in medium containing
      145 ng/ml of S. foetida extract (100 ng/ml SA) or 145 ng/ml OA (control) for 90
      min. Then tissue was washed and reincubated in medium containing 25 micrograms
      22(R)-hydroxycholesterol/ml or 25 micrograms pregnenolone/ml for 120 min. Tissue
      plus medium was analyzed for P4. Injection of SA or OA on Day 18 of gestation
      reduced (p < 0.01) serum levels of P4 within 24 h; concentrations of P4 then
      remained low, and relatively constant, in six OA control ewes that were pregnant
      until Day 30 of gestation and in three SA-treated ewes that had nonviable fetuses
      on Day 30. Serum concentrations of P4 in SA-treated ewes were lower than those of
      control ewes (p = 0.009). The remaining three ewes injected with SA exhibited
      estrus within 3 to 5 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142544
TI  - Transmission of relaxin from lactating bitches to their offspring via suckling.
AB  - The 6-kDa polypeptide hormone relaxin (Rlx) has been identified in human and
      bovine milk, and we recently reported its presence in canine milk. We postulated
      that Rlx might be transferred via suckling to the newborn pups, where, by virtue
      of its known effects to increase the distensibility of the pelvic connective
      tissues, it could play a role in causing the excessive laxity of the capsule and
      ligaments of the coxofemoral joint that precedes the development of hip dysplasia
      in genetically predisposed animals. Rlx was found in the serum of dysplastic
      (HD+) bitches for up to 6 wk of lactation, whereas it was detected in the serum
      of nondysplastic (HD-) bitches for only 1-2 wk of lactation. Rlx concentrations
      in milk were up to 60-fold greater than in serum. Milk Rlx levels varied
      markedly, but were highest during the first week of lactation and decreased
      thereafter. There were no significant differences in milk Rlx concentrations
      between HD+ and HD- bitches. Although the source of Rlx in milk is unknown, it
      cannot be the ovary or uterus, since hystero-ovariectomy performed at the time of
      cesarean section did not eliminate Rlx from milk during subsequent lactation. In
      serum samples taken from newborn pups before suckling, there were significant
      quantities of Rlx, demonstrating that the hormone enters the fetus in utero.
      However, Rlx rapidly disappears from serum of pups prevented from suckling for
      five hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142545
TI  - Development of glucose utilization studied in single oocytes and preimplantation
      embryos from mice.
AB  - Superovulated mouse oocytes and embryos were isolated and incubated with
      nontracer concentrations of 2-deoxyglucose, an analog of glucose, which is
      transported into the cells by glucose transporter and phosphorylated by
      hexokinase to 2-deoxyglucose 6-phosphate; it is not rapidly metabolized further,
      and accumulates in the cytosol. Using our non-radiometric and enzymatic
      microassay method, we determined 2-deoxyglucose and 2-deoxyglucose 6-phosphate
      amounts in individual oocytes and preimplantation embryos after the incubation.
      Hexokinase activity increased continuously and exponentially during development
      from follicular oocytes to blastocysts. Endogenous glucose and glucose 6
      phosphate decreased precipitously from follicular oocytes to unfertilized and
      ovulated oocytes. Fertilization induced rapid increases in glucose and glucose 6
      phosphate concentrations, which increased exponentially thereafter during
      embryonic development. 2-Deoxyglucose incorporation and 2-deoxyglucose 6
      phosphate formation were undetectable in unfertilized oocytes. However, when
      cumulus-oocyte complexes were incubated with 2-deoxyglucose, 2-deoxyglucose was
      incorporated into cumulus cells surrounding follicular oocytes and transported
      via the gap junctions into the follicular oocytes. Fertilization triggered
      facilitative 2-deoxyglucose transport in one-cell embryos, and the capacities of
      2-deoxyglucose incorporation and 2-deoxyglucose 6-phosphate formation developed
      along with the maturation of preimplantation embryos.

PMID- 8142546
TI  - Testosterone effects on spermatogenesis in the gonadotropin-releasing hormone
      immunized rat.
AB  - Active immunization of adult rats with a GnRH fusion protein was used to inhibit
      gonadotropin secretion and to establish an in vivo model for studying the
      hormonal control of spermatogenesis. The model was characterized in terms of the
      efficacy of the immunogen as well as the time course and nature of the
      immunological and biological responses. To study the reinitiation of
      spermatogenesis, testosterone (T) was chosen for this initial study as it is
      known to restore spermatogenesis in gonadotropin-deficient rats. Adult Sprague
      Dawley rats were actively immunized with a proprietory GnRH immunogen (BA-11, 100
      micrograms s.c.) every 4 wk. After 12 wk, 58% of animals showed markedly
      suppressed testicular size, as assessed by scrotal palpation, and were classed as
      responders. Serum LH, FSH, and T as well as the testicular elongated spermatid
      count (ESC) and epididymal sperm were undetectable in responding animals. Marked
      reductions in testicular (29% of control), prostatic (8% of control), and
      epididymal (32% of control) weights were seen. Spermatogenesis was severely
      disrupted with no evidence of progression beyond round spermatids. To study the
      action of T in GnRH-immunized animals, T (defined by lengths of s.c. silastic
      implant, T3-T24 cm) was given to responding animals. Animals were killed 2, 8,
      and 12 wk after T24 administration. In response to T24, serum T levels increased
      to 4 times control levels, serum FSH levels were restored to 65% of control
      levels by 2 wk, and serum LH remained undetectable. Testicular weight increased
      to 80% of control levels at 12 wk (p < 0.05 vs. control). Epididymal and
      prostatic weights were normalized by T. ESC increased to 82% of control values at
      12 wk (110 +/- 10 vs. control 134 +/- 8 million/testis, p = 0.001).
      Spermatogenesis was histologically normal after 8 wk of T24 treatment. To study
      the time course and dose response of T action, animals were immunized with
      another GnRH immunogen (BA-17), which yielded an 87% response rate at 12 wk.
      Testicular weight increased by Day 5 of T24 treatment, and a clear dose-response
      effect was apparent. The restoration of ESC was delayed compared to that of
      testicular weight (no restoration at 2 wk) and required > or = T6 treatment. Rats
      immunized for 20 wk and then given T24 treatment showed a similar pattern of
      restoration in testicular weight and ESC. Serum FSH was normalized by Day 2 of T
      treatment by doses > or = 3 cm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8142547
TI  - Diurnal expression of Fos in luteinizing hormone-releasing hormone neurons of
      Syrian hamsters.
AB  - The aim of the present study was two-fold: first, to examine the temporal
      relationship between increased expression of Fos in LHRH neurons of proestrous
      hamsters and increased plasma levels of LH, FSH, estradiol-17 beta (E2), and
      progesterone (P4); and second, to establish whether male hamsters, like females,
      also show diurnal variations in the number of LHRH neurons expressing Fos. Blood
      samples were collected from proestrous females at 0900 n, 1200 h, 1500 h, and
      1800 h and also from males at 0300 h, 0900 h, 1500 h, and 2100 h. RIA of the
      plasma revealed significant peaks of LH, FSH, and E2 at 1500 h, and of P4 at 1800
      h in the females; a significant but smaller peak of LH also occurred at 1500 h in
      the males. Double-label immunocytochemistry, using antibodies directed against
      amino acids 127-152 of the human Fos protein and against LHRH, showed that female
      hamsters expressed Fos in fewer than 10% of their LHRH neurons during the morning
      and at noon of proestrus but in approximately 41% of these neurons during the
      late afternoon (1800 h). In contrast, no expression of Fos occurred in LHRH
      neurons of male hamsters at any time of the day. The finding that the females
      showed an increase in the number of LHRH neurons expressing Fos after, and not
      before, the initiation of the preovulatory gonadotropin surge is significant
      because it does not readily support the hypothesis that this expression of
      immediate-early genes is in some way associated with the induction of the surge.
      Instead, the results are consistent with the view that expression of Fos in LHRH
      neurons reflects either the activation of a mechanism responsible for terminating
      the surge or, alternatively, the activation of a compensatory mechanism
      responsible for replenishing depleted neuropeptide stocks.

PMID- 8142548
TI  - Restoration of oocyte maturational competency during the nonbreeding season with
      follicle-stimulating hormone stimulation in squirrel monkeys (Saimiri boliviensis
      boliviensis).
AB  - The in vitro maturation potential of oocytes retrieved during the nonbreeding
      season with or without prior in vivo low-dose FSH stimulation was studied in
      adult squirrel monkeys (Saimiri boliviensis boliviensis). Additionally, the
      adequacy of various protein supplements in media used for oocyte maturation was
      investigated. Ovaries were removed from animals in the nonbreeding season (n = 9)
      with or without prior treatment with a low dose (1 mg) of FSH for four days
      before ovariectomy. Minimal estradiol elevation was observed in serum even with
      stimulation. For oocyte collection, ovaries were placed in warmed 21 mM HEPES
      buffered Ham's F-10. Oocytes from unstimulated ovaries were retrieved and
      cultured (47 of 62 recovered) in bicarbonate-buffered Ham's F-10 medium
      containing 0.5% BSA as protein supplement. Negligible maturation was observed at
      48 h (3 of 47; 6%), and no fertilization was seen after insemination. Immature
      oocytes from animals stimulated with a low dose of FSH were cultured (69 of 94
      recovered). With prior FSH stimulation, oocytes placed in 0.5% BSA medium matured
      (13 of 24; 54%) and fertilized (7 of 21; 33%) in marked contrast to oocytes from
      the nonstimulated monkeys. Additionally, 20% monkey serum and 20% human
      follicular fluid were studied as alternative protein supplements for the FSH
      pretreated oocytes; these produced similar maturation rates (10 of 22, 45%; 10 of
      23, 43%, respectively) and fertilization rates (8 of 21, 38%; 6 of 21, 29%,
      respectively). In some cases, 2 pronuclei were observed at 16 h and 4 cells were
      observed at 40 h. Of those activated, 63% showed cleavage ranging from 2 to 8
      cells by 96 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142549
TI  - Expression of connexin 43 gap junction messenger ribonucleic acid and protein
      during follicular atresia.
AB  - The process of atresia is an all-or-none phenomenon in that an entire follicle
      either undergoes atresia or continues along the developmental pathway. The
      absence of pockets of atresia adjacent to healthy areas of granulosa cells
      suggests the existence of a coordinating influence within the entire follicular
      unit during the process of atresia. Gap junctions interconnect the granulosa
      cells and the oocyte in the ovarian follicle, forming a metabolic syncytium.
      Intercellular communication provided via the gap junctions may play a role in
      coordinating the process of atresia. This study addresses the potential hormonal
      regulation of the gap junction gene during the process of atresia. Immature
      female rats were given an estradiol (E2) implant to induce follicular
      development, and after 48 h the E2 was withdrawn to induce atresia. The ovary is
      an extremely heterogeneous tissue with multiple cell types and many follicles at
      different stages of development. Therefore, in situ hybridization and
      immunocytochemistry were ideal techniques to localize gap junction gene
      expression precisely to specific cells in the ovary. Observations resulting from
      these studies revealed that while the granulosa cells of healthy, developing, pre
      antral and antral follicles expressed large amounts of connexin 43 (cx 43) gap
      junction mRNA and protein, this expression was greatly reduced in atretic
      follicles. In the follicles undergoing atresia, the levels of cx 43 gap junction
      mRNA and protein were reduced as early as 6 h after the withdrawal of E2. The
      levels of cx43 mRNA and protein continued to decrease as atresia progressed, and
      at 11 h after withdrawal of E2 very little cx43 mRNA or protein was seen. These
      results indicate that gap junction mRNA and protein are decreased in association
      with atresia and support the hypothesis that a loss of gap junctional
      communication plays a coordinating role in the process of atresia.

PMID- 8142550
TI  - Changes in levels of messenger ribonucleic acid for cytochrome P450 side-chain
      cleavage and 3 beta-hydroxysteroid dehydrogenase during prostaglandin F2 alpha
      induced luteolysis in cattle.
AB  - Regression of the CL causes a dramatic decrease in plasma progesterone levels. To
      test the hypothesis that the decrease in progesterone involves the down
      regulation of mRNA encoding the steroidogenic enzymes, cytochrome P450 side-chain
      cleavage (P450scc) and/or 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD),
      levels of plasma progesterone and luteal mRNA for P450scc and 3 beta-HSD were
      measured and correlated during induced luteolysis. Holstein heifers (n = 25) were
      injected with 25 mg prostaglandin F2 alpha (PGF2 alpha) on Day 6 or 7 of the
      estrous cycle (Day 0 = estrus) to induce luteal regression. To determine acute
      changes in plasma progesterone during luteolysis, jugular blood samples were
      obtained from 5 heifers hourly for 12 h, beginning immediately before injection
      of PGF2 alpha, and assayed for progesterone by RIA. A significant decrease in
      plasma progesterone levels was observed as early as 1 h after the PGF2 alpha
      injection (3.62 vs. 2.72 ng/ml, p < 0.05). Progesterone levels continued to
      decline with time through 12 h after administration of PGF2 alpha. The other 20
      animals were ovariectomized at 0 (n = 6), 2 (n = 4), 12 (n = 4), or 24 (n = 6) h
      after PGF2 alpha. Levels of P450scc and 3 beta-HSD mRNA were determined in
      extracts of total luteal RNA by ribonuclease (RNase) protection assay. By 2 h
      after PGF2 alpha, 3 beta-HSD mRNA levels had decreased by about 40% as compared
      with levels at time 0 (p < 0.05), and a further significant decrease occurred
      between 2 and 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142551
TI  - Constitutive and regulated prolactin secretion: effects of estradiol.
AB  - We have utilized a combined reverse hemolytic plaque/in situ hybridization assay
      to assess the relationship between individual cell secretion of prolactin and the
      level of prolactin gene expression within the same cell. It is thought that cells
      utilizing predominantly a constitutive pathway of protein secretion will exhibit
      a direct relationship between the level of secretion and that of gene expression.
      In contrast, cells that are secreting protein predominantly from stored pools
      exhibit no relationship between these two parameters since secretion does not
      depend upon synthesis of new hormone. In addition, regulated protein secretion
      depends upon calcium; therefore, regulated secretion is inhibited by calcium
      channel blockers such as nifedipine. We tested whether the presence of estradiol
      influences the proportion of hormone secreted by the constitutive and regulated
      pathway by 1) assessing whether estradiol changes the relationship between gene
      expression and secretion in individual cells and 2) measuring the effects of
      nifedipine on prolactin secretion. Our data demonstrate that estradiol priming
      results in a direct relationship between the amount of hormone secreted by an
      individual lactotroph and the level of prolactin mRNA in the same cell; the
      findings also show that prolactin secretion from lactotrophs of estradiol-treated
      rats is not suppressed by nifedipine. Therefore, we conclude that estradiol
      enhances the proportion of hormone that is secreted via a constitutive pathway.

PMID- 8142552
TI  - Site of macrophage inhibition of luteinizing hormone-stimulated testosterone
      production by purified leydig cells.
AB  - It has been observed that testicular macrophages and testicular macrophage
      conditioned medium reduce LH-stimulated, but not basal, testosterone production
      by purified Leydig cells in vitro. In order to determine how this inhibition
      occurs, we have examined the effects of testicular macrophages and testicular
      macrophage-conditioned medium at discrete stages of the steroidogenic pathway.
      The lesion in steroidogenesis is located at a step beyond cAMP formation, because
      the addition of dibutyryl cAMP or cholera toxin did not overcome the testicular
      macrophage-conditioned medium inhibition of LH-stimulated steroidogenesis by
      Leydig cells. This effect of testicular macrophage-conditioned medium on Leydig
      cell testosterone production is first observed at 18 h after initiation of
      culture. However, subsequent additions of 22R-hydroxycholesterol, pregnenolone,
      dehydroepiandrosterone, or androstenedione to the Leydig cell cultures can
      overcome the inhibition so that, after a further 6 h of incubation, testosterone
      production is not significantly different from that of control Leydig cells
      cultured in the absence of testicular macrophage-conditioned medium. These
      results suggest that the block in steroidogenesis is beyond cAMP production but
      prior to the formation of pregnenolone, dehydroepiandrosterone, and
      androstenedione. Since the medium for these cultures contained lipoprotein, it is
      possible that the testicular macrophage-conditioned medium metabolizes the
      lipoprotein, making it unavailable to the Leydig cells. However, our results show
      that preincubation of lipoprotein with testicular macrophage-conditioned medium
      does not significantly alter testosterone production by the Leydig cells in the
      culture. It is concluded that testicular macrophage-conditioned medium affects
      the transport or availability of cholesterol to mitochondria prior to further
      steps in the steroidogenic pathway.

PMID- 8142553
TI  - Effects of photoperiod on reproduction and the gonadotropin-releasing hormone
      immunoreactive neuron system in the postpubertal male Djungarian hamster.
AB  - The present study tested the hypothesis that photoperiodic control of
      reproductive function in the postpubertal Djungarian hamster is associated with
      changes in the number, morphology, or distribution of GnRH-immunoreactive cell
      bodies in the brain. To initiate or arrest sexual maturation, males were reared
      in long (LD, 16L:8D) or short (SD, 10L:14D) days from birth. In two other groups
      that were chronologically past the normal onset of puberty, males were
      transferred at 30 days of age from LD to SD or from SD to LD to arrest or
      initiate reproductive function, respectively. At 40, 60, or 90 days of age, 4-6
      hamsters in each of the four photoperiod treatment groups were killed by
      intracardiac perfusion. Testes weights were significantly increased in males
      exposed to long days (LD and SD-to-LD groups) compared to those treated with
      short days (SD and LD-to-SD groups). Serum FSH concentrations at 40 days of age
      were also increased in the two groups of males in long days compared to those in
      both groups in short days (p < 0.05, ANOVA); LH concentrations were unaffected by
      photoperiod treatments. Brain sections (60 microns) from the corpus callosum
      decussation to the suprachiasmatic nucleus in the anterior hypothalamus were
      processed for GnRH immunocytochemistry. In brain regions that contained the
      majority of GnRH neurons, i.e., the medial preoptic area and diagonal band of
      Broca, the numbers of GnRH-immunoreactive cell bodies were the same among the
      four treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142554
TI  - Prolactin stimulates emission of nipple pheromone in ovariectomized New Zealand
      white rabbits.
AB  - Using ovariectomized New Zealand white rabbits and the nipple-search behavior of
      pups as a bioassay, we evaluated the capacity of prolactin to stimulate the
      emission of an odor signal that allows newborn pups to locate the mother's
      nipples and suckle. Whereas emission of this so-called nipple pheromone was
      minimal in untreated, ovariectomized does, emission was stimulated by the
      administration of progesterone (1 mg/day) to estrogen-treated does (0.5 microgram
      estradiol benzoate/day) and decreased after withdrawal of progesterone despite
      continuous administration of estrogen. However, substituting ovine prolactin (1.5
      mg/day) for progesterone, under continuous estrogen administration, resulted in
      an increase in pheromone emission to near-maximal levels. This stimulatory effect
      of prolactin was not progesterone-dependent since it also occurred in does
      pretreated with estrogen alone and, to a lesser extent, even in females without
      estrogen priming. From these and previous data, we propose that emission of
      nipple pheromone in the rabbit is induced during pregnancy by the combined action
      of estrogen and progesterone, and maintained during lactation by the dual action
      of estrogen and prolactin.

PMID- 8142555
TI  - Regulation of cell-cell communication mediated by connexin 43 in rabbit
      myometrial cells.
AB  - The aim of this study was to evaluate the rapid regulation of cell-cell
      communication by using the microinjection of purified cAMP-dependent protein
      kinase (protein kinase A), the Ca(2+)-phospholipid-dependent protein kinase
      (protein kinase C), or the inhibitor proteins (PKI and CKI) that are,
      respectively, specific for each of these enzymes. Gap junction phenotypes of
      myometrial tissue and cells were studied by means of immunocytochemistry with
      antibody to connexin 43 (alpha 1; Cx43). Cells were enzymatically disaggregated
      from myometrium of nonpregnant, mid-pregnant (Day 14), and late-pregnant (Day 29)
      rabbit uteri (n = 8 per group) and seeded at high density such that after 4 days,
      cultures had the appearance of a cross-sectioned myometrium. Purified proteins
      and their subunits were microinjected, and intercellular communication was
      evaluated by monitoring Lucifer Yellow dye transfer. Cultures were treated with
      0.5 mM 8Br-cAMP (8-bromo adenosine 3',5' cyclic monophosphate) or 10 microM OAG
      (1-oleoyl-2-acetyl-sn-glycerol), which, respectively, activate protein kinase A
      and protein kinase C. Immunoreactive Cx43 and cell-cell communication were
      examined 5 min to 2 h later. Cx43 was detected in myometrial cryosections and
      cultured cells by indirect immunofluorescence, and its expression increased with
      gestation. Exposure to 8Br-cAMP increased the amount of immunoreactive Cx43.
      Basal dye transfer was minimal in nonpregnant cells, increased in cells of mid
      pregnant uteri, and was maximal in late-pregnant cells. Treatment with 8Br-cAMP
      enhanced transfer in mid- and late-pregnant cells but had no obvious effect on
      cells from nonpregnant animals. OAG treatment inhibited dye transfer in greater
      than 95% of the cells tested irrespective of pregnancy status. PKI inhibited cell
      cell communication within 2 min and up to 40 min. Injection of free catalytic
      subunit of protein kinase A following PKI inhibition restored communication
      within 2-3 min, with maximal transfer in 4-5 min. Protein kinase C inhibited
      communication, which resumed in < 3 min after injection of CKI. We conclude that
      rabbit myometrial cells engage in Cx43-mediated cell-cell communication and that
      this process increases during pregnancy. Further, activators of protein kinase A
      or injected free catalytic subunit rapidly enhances cell-cell communication,
      whereas activators of protein kinase C or the enzyme itself diminishes this
      process.

PMID- 8142556
TI  - Enhanced rates of cleavage and development for sheep zygotes cultured to the
      blastocyst stage in vitro in the absence of serum and somatic cells: amino acids,
      vitamins, and culturing embryos in groups stimulate development.
AB  - The aim of this study was to develop a serum-free culture system that could
      support high levels of cleavage and blastocyst formation from sheep zygotes
      developed in vitro. To this end, we investigated the effects on sheep zygote
      development of amino acids, ammonium, vitamins, and culture of embryos in groups
      in Synthetic Oviduct Fluid (SOF) medium supplemented with BSA (32 mg/ml). The
      inclusion of amino acids in the culture medium had no effect on the percentage of
      embryos arrested at the 8-16-cell stage when embryos were cultured singly in the
      same drop of medium for 6 days (43% in SOF; 41% in SOF+amino acids). However, in
      medium containing all Eagle's amino acids, replacing the culture medium every 48
      h to alleviate ammonium toxicity significantly decreased the number of arrested
      embryos (6%; p < 0.05) and significantly increased blastocyst cell number (52
      cells in SOF; 105 cells in SOF+amino acids; p < 0.01) and the number of embryos
      developing to the blastocyst stage (29% in SOF; 67% in SOF+amino acids; p <
      0.05). When the medium was renewed every 48 h, nonessential amino acids and
      glutamine also significantly decreased the number of arrested embryos (p < 0.05).
      Culturing embryos singly or in groups in SOF medium with all Eagle's amino acids
      that was renewed every 48 h resulted in significant increases in blastocyst
      hatching and mean cell number (47%, 31%, and 79%; 105, 136, and 173 cells for
      embryos cultured singly, in groups of 2, and in groups of 4, respectively). After
      culture in groups of 4, blastocyst cell numbers were equivalent to in vivo
      developed controls (160 cells) and significantly greater than those developed in
      serum (103 cells; p < 0.01). Analysis of blastocyst metabolism, expressed on a
      per-cell basis, revealed that amino acids did not affect either glucose uptake or
      lactate production, whereas the addition of amino acids and vitamins resulted in
      a significant increase in both parameters (p < 0.01). A similar response was
      observed in serum-derived blastocysts. Ammonium production by sheep blastocysts
      after culture in the presence of amino acids was significantly greater than that
      produced by mouse blastocysts, indirect evidence that ruminant embryos utilize
      amino acids to a greater extent than do rodent embryos.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8142557
TI  - Structure of the alpha-inhibin gene and its regulation in the ruminant gonad:
      inverse relationship to oxytocin gene expression.
AB  - The genes for the alpha subunit of inhibin and for the nonapeptide hormone
      oxytocin are both expressed in the granulosa cells of the ruminant follicle as
      well as in the Sertoli cells of the ruminant testis. Northern hybridization of
      mRNA from both ovary and testis indicate that in both gonads the expression of
      the two genes is inversely regulated. In the luteinizing granulosa cells, in
      vitro as in vivo, the alpha-inhibin gene is down-regulated when the oxytocin gene
      is up-regulated. In the Sertoli cells of the bull and sheep testis, the situation
      is similar, with the alpha-inhibin gene being up-regulated in the prepubertal
      gonad and down-regulated concomitantly with an up-regulation of the oxytocin gene
      in early puberty. The gene for the bovine alpha-inhibin subunit was cloned and
      characterized. Assessment of transcriptional initiation by primer extension and
      ribonuclease protection assays showed that several different sites were used in
      both granulosa cells and testis. Transient transfection of primary bovine
      granulosa cells with alpha-inhibin/luciferase gene constructs indicated that a
      major promoter element resided in the region -178 to -245 respective to the
      methionine start codon of translation, a region that contains a cAMP response
      element. The ability of forskolin to up-regulate the transcription of transfected
      gene constructs also depended on the integrity of this region. In contrast,
      transfection of TM4 cells led to transcriptional initiation from an unusual site
      in the alpha-inhibin gene and to a lack of forskolin regulation. Comparison of
      the alpha-inhibin and oxytocin genes indicates that although both can be up
      regulated by FSH or by forskolin within the same cells, different mechanisms of
      signal transduction are involved to explain the temporal differences in
      expression. Together the results indicate that a differentiation step occurring
      in Sertoli cells at early puberty and in granulosa cells at luteinization
      involves comparable regulation of genes through the sequential action of
      different cAMP-linked transcription factors.

PMID- 8142559
TI  - Relationship between the supply of primordial follicles and the onset of
      follicular growth in rats.
AB  - Primordial follicles enter a state of suspended animation when they are formed
      and constitute a "stockpile" from which all growing follicles are derived. The
      factors that release individual follicles from their quiescent state are unknown.
      Many investigators believe that the number of follicles in the primordial
      stockpile is a major factor in determining the rate at which follicles begin to
      grow. However, the relationship between the size of the stockpile of primordial
      follicles and the rate at which follicles move into the growing pool is unclear.
      The purpose of the present study was to attempt to clarify this relationship. The
      initial size of the stockpile of primordial follicles was experimentally reduced
      by exposing rats to various doses of busulphan (BUS) in utero. Ovaries were
      collected at various ages postpartum and prepared for histological analysis. A
      computer-controlled image analyzer was used to perform size/frequency analysis of
      oocytes in control and treated ovaries; onset of follicular growth was recognized
      by enlargement of the oocyte. There was an inverse correlation between the number
      of primordial follicles in the ovary at birth and the rate at which they moved
      into the growing pool. In rats most severely affected by the BUS, all of the
      remaining follicles began to grow very early in life. By the time these severely
      affected rats reached adulthood, the stockpile of primordial follicles had been
      nearly exhausted. Nevertheless, the number of large antral follicles remained at
      normal levels until the follicular reserve was completely depleted.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8142558
TI  - Influence of extracellular matrix gradients on the haptotactic migration of F9
      embryocarcinoma-derived primitive and parietal endoderm-like cells.
AB  - The establishment of the parietal endoderm (PE) layer within the rodent
      blastocyst requires extensive outward migration of inner cell mass (ICM)-derived
      primitive endoderm (PrE) cells over the blastocoelic surface of the
      trophectoderm. While a role for Reichert's membrane in this process has been
      proposed, the identity of the basement membrane component(s) involved and the
      mechanism(s) by which they might promote and/or guide this movement remain to be
      determined. This study was a comparison of the gradient-associated influences of
      three components of Reichert's membrane--fibronectin, laminin, and collagen IV-
      on the migration of embryonic endoderm-like cells obtained from the F9
      embryocarcinoma cell line. Gradients (positive or negative) or even coatings of
      each of these glycoproteins were established across polycarbonate filters; the
      filters were then placed in blind-well chambers. F9 cells, either
      undifferentiated or pretreated with retinoic acid (RA) alone or RA+dibutyryl cAMP
      to resemble PrE and PE, respectively, were then loaded into the upper chamber
      compartments. At the end of the migration assay (4-24 h), the number of cells
      that had moved through the filter pores and attached to the lower filter surface
      was determined for each treatment group. While even coatings of either
      fibronectin or laminin supported some cell migration through the filters, these
      levels were increased 13- and 20-fold (fibronectin and laminin, respectively) by
      application of the glycoproteins as positive gradients. In contrast, no migration
      occurred in response to negative gradients of either fibronectin or
      laminin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142560
TI  - Expression of mannose 6-phosphate receptor messenger ribonucleic acids in mouse
      spermatogenic and Sertoli cells.
AB  - Spermatogenic and Sertoli cells isolated from the mouse synthesize different
      proportions of the two mannose 6-phosphate receptors (MPR) during overnight
      culture periods (O'Brien et al., Endocrinology 1989; 125:2973). To determine the
      relative expression of MPR mRNAs in these cells, poly(A)+ RNAs were examined by
      Northern blot analysis using cDNA probes specific for the cation-independent (CI)
      and cation-dependent (CD) MPRs. A single CI-MPR transcript, approximately 10 kb
      in size, was present in all tissues and cell types examined. Like the CI-MPR
      protein, this transcript was more abundant in Sertoli cells than in spermatogenic
      cells isolated from adult testes. The CD-MPR is the predominant MPR synthesized
      by pachytene spermatocytes or round spermatids. Multiple CD-MPR transcripts were
      detected in these cells, including a 2.4-kb CD-MPR mRNA that was
      indistinguishable from CD-MPR transcripts in somatic tissues and Sertoli cells.
      Smaller CD-MPR mRNAs of approximately 1.4 and 1.6 kb were prominent in pachytene
      spermatocytes and round spermatids, respectively, but were faint or undetectable
      in somatic tissues. These smaller CD-MPR mRNAs did not hybridize with an 0.9-kb
      restriction fragment derived from the CD-MPR 3' untranslated region (UTR),
      suggesting that alternate polyadenylation signals are used to produce multiple CD
      MPR transcripts in spermatogenic cells. When poly(A) tracts were selectively
      removed from germ cell RNAs by ribonuclease H treatment, identical 1.3-kb CD-MPR
      mRNAs were detected in pachytene spermatocytes and round spermatids, indicating
      that the size difference between the 1.4- and 1.6-kb transcripts is due to
      variations in poly(A) tail length.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142562
TI  - Immunohistochemical localization of the interleukin-1 system in the mouse ovary
      during follicular growth, ovulation, and luteinization.
AB  - The distribution of immunoreactive interleukin-1 receptor type I (IL-1R tI), IL-1
      alpha, and IL-1 beta, and of macrophages, was investigated immunohistochemically
      in the mouse ovary during follicular growth, ovulation, and luteinization. For
      this purpose, an indirect immunofluorescence technique, using specific monoclonal
      antibodies against mouse IL-1R tI, mouse IL-1 alpha, IL-1 beta, and macrophage
      antigens (CD11b/CD18) was used with sections of paraffin-embedded ovaries from
      eCG and eCG/hCG-treated 12-wk-old B6C3F-1 female mice. During follicular
      development, IL-1 alpha, IL-1 beta, and IL-1R tI staining were confined to the
      theca-interstitial layer of growing follicles with one remarkable exception.
      Intense IL-1R tI still staining was present in the cytoplasm and plasma membrane
      of the murine oocyte. During ovulation, IL-1 alpha and IL-1 beta were still
      confined to the theca layer, but faint IL-1R tI staining was initiated in cumulus
      cells and in granulosa cells just before follicle rupture. Immediately after
      follicle rupture, granulosa cells stained positive for IL-1R tI, IL-1 alpha, and
      IL-1 beta. During luteinization, granulosa-luteal cells of the corpus luteum
      demonstrated strong IL-1R tI, IL-1 alpha, and IL-1 beta staining. Macrophages
      were detected in the theca layer and stroma, but never within the follicle before
      ovulation. Immediately after ovulation, there was a rapid entry of macrophages
      into the follicle, and macrophages were also present inside the corpus luteum.
      Our morphological results support a possible autocrine-paracrine role of the
      mouse ovarian IL-1 system in ovulation and luteinization.

PMID- 8142561
TI  - Aromatase activity in developing guinea pig brain: ontogeny and effects of
      exogenous androgens.
AB  - The formation of estrogens from androgens by aromatase in the developing brain is
      an important step in the sexual differentiation of many species. We characterized
      aromatase activity (AA) in a high-speed pellet of brain tissue from fetal guinea
      pigs. The apparent substrate affinity (approximately 17 nM) was comparable to
      reported values in other species. Aromatase activity was highest in the amygdala
      (AMG) and preoptic area (POA), with lesser amounts in the septum (SEPT) and
      medial basal hypothalamus (MBH). Activity was low but measurable in parietal
      cortex (CTX). In the AMG, POA, SEPT, and MBH, AA was highest in early gestation
      (Days 35-40) and showed a steady decline through development. No sex difference
      in AA was apparent. We also determined the effects of administration of exogenous
      androgens to pregnant females on brain AA in the fetus. Testosterone propionate
      (5 mg/day on Days 30-39 followed by 1 mg/day on Days 40-50) caused a significant
      increase (p < 0.05) in AA found in the MBH and CTX. Administration of
      dihydrotestosterone propionate (2.5 mg/day on Days 30-39 followed by 1 mg/day on
      Days 40-50) significantly stimulated AA in SEPT, MBH, and CTX. These data
      demonstrate that the fetal guinea pig brain contains high levels of AA during the
      critical period of sexual differentiation. Treatment with high levels of
      exogenous androgens consistently induces AA in the MBH and CTX. These latter
      effects may be among the mechanisms through which exogenous androgens act on the
      developing brain.

PMID- 8142563
TI  - [Health risks from inhalation anesthetics].

PMID- 8142564
TI  - [Difficulties in the relaxometry of diabetics].
AB  - OBJECTIVE: Based upon clinical experience, peripheral nerve stimulation for
      neuromuscular monitoring under general anesthesia sometimes seems to be difficult
      in patients with diabetes mellitus. The aim of this study was to evaluate the
      applicability of the evoked electromyogram (EMG) in diabetics compared to non
      diabetic controls. METHODS: 109 ophthalmosurgical patients (35 diabetics, 74 non
      diabetics) were investigated. Relaxometry was performed by electrical stimulation
      of the ulnar nerve proximal of the wrist and the evoked EMG was recorded above
      the hypothenar muscle (Relaxograph, supplied by Datex). Immediately after
      induction of anaesthesia the calibration of the device was performed. RESULTS:
      The calibration of the relaxograph could be performed successfully only in 57.1%
      of the diabetics compared to 93.2% of the non-diabetics (p < 0.001). Consequently
      the uncalibrated mode had to be chosen more often in diabetics than in non
      diabetics. In two non-diabetics and three diabetics no stimulation response could
      be achieved. Biometrical data, serum electrolyte concentrations, wrist
      circumference and body temperature were similar in both groups. The calibration
      mode could be performed in diabetics without peripheral polyneuropathy more often
      (76.5%) than in diabetics with peripheral polyneuropathy (38.9%) (p < 0.05).
      CONCLUSION: The results show that the applicability of the peripheral nerve
      stimulator in diabetic patients is more difficult than in non-diabetics. The
      disturbances of the peripheral nervous system seem to be responsible for these
      problems.

PMID- 8142565
TI  - [Abdominal complications following heart surgery].
AB  - OBJECTIVE: Intra-abdominal complications occurring after cardiopulmonary bypass
      operations are rare but often fatal. There are only speculative approaches
      concerning the pathogenesis and the risk factors of these complications. The aim
      of our study was therefore to determine the causative factors and to evaluate the
      diagnostic and therapeutic measures, because early diagnosis and immediate
      treatment is essential for the outcome of the patients. DESIGN: 500 consecutive
      patients who underwent cardiopulmonary bypass procedures over a period of 14
      months were examined for intra-abdominal complications. The records of these
      patients were reviewed in relation to possible risk factors and the group with
      intra-abdominal complications was compared with a random sample of 50 patients in
      respect of possible risk factors. The diagnostic procedures (serum lactate
      concentrations, sigmoidoscopy, coloscopy) and the therapeutic interventions were
      also evaluated. MAIN RESULTS: 9 (1.8%) of the 500 patients developed intra
      abdominal complications. The mortality rate was 44% (4 of 9). 5 patients had
      bowel necrosis or ischaemic colitis. Pseudo-obstruction appeared in 5 cases. One
      patient developed cholecystitis and one acute haemorrhagic pancreatitis.
      Gastroduodenal complications were not observed. There was no difference between
      the group with intra-abdominal complications and the random sample with regard to
      sex, type of operation and preoperative intra-abdominal diseases. Clinical risk
      factors identified were: age, occlusive vascular disease, atrial fibrillation,
      prolonged aortic cross-clamping times and mean bypass times, intraoperative and
      postoperative need for supply of epinephrine and norepinephrine, implantation of
      an intraaortic balloon counterpulsation pump, low cardiac output, postoperative
      multiple organ failure. 8 out of the 9 patients had severe intraoperative
      surgical complications or general complications in the postoperative course. All
      patients with bowel necrosis or ischaemic colitis had abnormal serum lactate
      concentrations. With the aid of sigmoidoscopy in one patient, only bowel necrosis
      or ischaemic colitis could be detected. In one patient with pseudoobstruction, an
      operation was probably obviated by decompression of the colon by coloscopy. 6 of
      the 500 patients after cardiopulmonary bypass required emergency laparotomy. Two
      patients with bowel necrosis were saved by early hemicolectomy. CONCLUSION: In
      reviewing both our results and data cited in earlier studies, intra-abdominal
      complications can generally be attributed to the following: Intraoperative
      surgical complications with the consequence of prolonged aortic cross clamping
      and total bypass times can cause low cardiac output and mesenteric hypoperfusion.
      Predominantly as a result of the low cardiac output, the use of vasopressors
      increases splanchnic ischaemia, in particular in patients with pre-existing
      occlusive vascular disease of the mesenteric arteries. Mucosal ischaemia might be
      aggravated by a concurrent pseudo-obstruction. On the other hand, intraoperative
      complications and low cardiac output can cause further complications and finally
      multiple organ failure. Multiple organ failure and ischaemia of the gut can
      initiate the vicious circle which is responsible for the high mortality from
      these complications. Early detection by careful physical examination and the
      combination of the diagnostic procedures and prompt treatment should lead to a
      reduction of mortality.

PMID- 8142566
TI  - [Eicosanoids as mediators in ARDS].
AB  - Eicosanoids partly develop from the metabolism of arachidonic acid through the
      cyclooxygenase or the lipoxygenase pathway. Lipoxygenase products are the
      leukotrienes (LTA4, LTB4, LTC4, LTD4, LTE4) and the 5-hydroxyeicosatetraenoic
      acid (5-HETE). Cyclooxygenase products are the prostanoids (prostaglandins [PG]
      D2, E2, F2, I2 and thromboxane A2). The other part of the eicosanoids develops
      from the metabolism of two other fatty acids over the same pathways; 8,11,14
      eicosatrienoic acid leads to the prostaglandins D1, E1, F1, I1 and the
      leukotrienes A3, B3, C3, D3, E3. From 5,8,11,14,17-eicosapentaenoic acid result
      the prostaglandins D3, E3, F3, I3 and the leukotrienes A5, B5, C5, D5, E5. The
      pathophysiological changes in ARDS are mainly due to an imbalance of opposing
      effects of mediators. In this regard eicosanoids play an important role which has
      not yet been clearly determined. Bronchoconstriction and pulmonary hypertension
      are increased by thromboxane A2 and leukotrienes, whereas they are reduced by
      PGI2. Pulmonary edema is enlarged by leukotriene, especially, LTB4, whereas PGI2
      has a protective effect. The aggregation of platelets is mediated through
      thromboxane A2, PGF2 and LTB4; PGE1 and PGI2 counteract these reactions. LTB4, in
      addition to 5-HETE, leads to the activation of inflammatory cells. Drug induced
      eicosanoid imbalances can be used for therapeutic interventions.

PMID- 8142567
TI  - Curt Schimmelbusch (1850-1895)--development of a mask for chloroform and ether
      anesthesia based on primary aseptic principles.
AB  - The German surgeon Curt Schimmelbusch is not generally recognised as a pioneer in
      anaesthesia, although he is well known by his investigations concerning the
      development and scientific foundation of mechanical sterilisation methods which
      he performed under Ernst von Bergmann in Berlin at the end of the 19th century.
      His book "Anleitung zur aseptischen Wundheilung" is one of the classics in the
      history of asepsis. Curt Schimmelbusch was born on November 16th, 1860, as the
      son of a lord of a manor in Gross-Nogath/West-Prussia. Having graduated from high
      school in 1882, he studied medicine at Wurzburg, Gottingen, Berlin and Halle. The
      physician who was awarded the doctor's degree in Halle in 1886 as a co-worker of
      the histologist and pathologist Eberth at first dealt with research in the field
      of thrombosis. His surgical training took place in Cologne where he worked in
      1888 with the famous surgeon Bardenheuer at the Burgerhospital. A year later he
      returned to Berlin to do research work at the institute at the Ziegelstrasse.
      Under the main aspects of hygiene he described a mask in 1890, which he used
      predominantly for ether anaesthesia, although he considered it to be suitable
      also for chloroform anaesthesia, in itself an exciting contribution he has made
      characterising the progress of anaesthesia in German-speaking countries up to the
      mid-50's of the 20th century.

PMID- 8142568
TI  - [SIRS--Systemic Inflammatory Response Syndrome].

PMID- 8142569
TI  - [SIRS (Systemic Inflammatory Response Syndrome) following trauma and during
      sepsis].

PMID- 8142570
TI  - [The significance of the liver for the course of SIRS (Systemic Inflammatory
      Response Syndrome) following shock, trauma and during sepsis].

PMID- 8142571
TI  - [The leukocyte-endothelial interaction as an expression of a hepatic inflammation
      reaction during an experimental shock syndrome].

PMID- 8142572
TI  - [Liver function disorders in critically ill patients: pathogenetic, diagnostic
      and therapeutic aspects].

PMID- 8142573
TI  - [A new method of pain sedation following thymectomy in myasthenia gravis. 2
      cases].
AB  - Two patients with myasthenia gravis were ventilated postoperatively using
      propofol and piritramide for analgosedation. Under this treatment the patients'
      ability to cooperate and communicate was maintained and allowed a patient
      controlled readjustment of pyridostigmine dosage and weaning from the respirator.

PMID- 8142574
TI  - [Successful treatment with hyperbaric oxygen following severe cerebro-arterial
      gas embolism].
AB  - We report on a patient suffering from a severe cerebral arterial gas embolism
      associated with decompression from a simulated high pressure chamber dive.
      Treatment with hyperbaric oxygen (HBO) commenced immediately after the accident
      and was continued subsequently for 8 weeks with a total of 49 HBO-sessions.
      Despite initial transitory amaurosis and flaccid tetraplegia lasting for two
      weeks the patient made a near complete recovery except for circumscript numbness
      and paraesthesia confined to the left tibia and palm. This case underscores the
      need to consider patients with cerebral arterial gas embolism for HBO treatment
      and the potential value of a subsequent long-term HBO therapy.

PMID- 8142575
TI  - Famous names in toxicology. Claude Bernard 1813-1878.

PMID- 8142576
TI  - Drug-induced gingival overgrowth.

PMID- 8142577
TI  - Factors influencing reactions to anti-convulsant drugs.

PMID- 8142578
TI  - A review of documentation requirements for preclinical sections, for marketing
      submissions in the European Community, Japan and the USA.
AB  - Standardization of the documentation requirements for preclinical sections, for
      marketing submissions in the European Community (EC), Japan and the USA is
      proposed. It is unnecessary to standardize the leading summaries of submissions
      as their format is predicated by the way in which the regulatory authorities
      review applications. Harmonization of the technical sections will reduce the
      duplication of effort expended by pharmaceutical companies to produce
      documentation specific for each regulatory authority. Elimination of requirements
      specific to individual authorities will further reduce the resource requirements.
      The proposals made in this paper are aimed to increase the 'user-friendliness' of
      the preclinical documentation and therefore expedite the review process.

PMID- 8142579
TI  - Drug-induced cutaneous vasculitis.

PMID- 8142580
TI  - [Torsion stability of coronary catheters].
AB  - In the present study, the torsional moments of 8 different types of catheter
      having two different calibres (n = 5 in each case) were investigated. The
      catheters were made of linear polyurethane (Cordis, Netherlands). The transmitted
      torsional moments of the 5.2 Fr. catheters positioned in a straight line were
      1.48 +/- 0.09 Ncm (VK = 6%), positioned in a 90 degree curve 1.39 +/- 0.11 Ncm
      (VK = 8%). The corresponding figures for the 6 Fr. catheters were 2.43 +/- 0.20
      Ncm (VK = 8%) and 2.26 +/- 0.20 Ncm (VK = 9%). The highly stable transmission
      behaviour in particular of the 5 Fr. catheters--with a variation coefficient of
      the torsional moments of 6%--is due mainly to the accurate manufacture of the
      catheters, and the material chosen. The study is a first step towards achieving
      systematic quality control of the materials used for diagnosis and therapy.

PMID- 8142581
TI  - [Development of a mathematical model for simulation of artificial ventilation].
AB  - This article describes a mathematical model for the simulation of artificial
      ventilation employing only the figures for air pressure and air flow between
      respirator and lungs. A discussion of methodological aspects of the problem shows
      that the model of the respiratory system can be reduced to an equivalent circuit
      diagram comprising only resistances and capacitances. The structure of the
      mathematical model is oriented to the elements of the real respiratory system,
      and its modularity permits ready adaptation to a variety of real-life situations.
      Particular emphasis was placed on the correct parametrization of the model with
      the aid of data originally collected from physical experiments. Finally, some
      selected model runs that demonstrate the range of validity and the accuracy of
      the model are presented.

PMID- 8142582
TI  - [Interactive, multimedia learning system for the study of primary open angle
      glaucoma--system description from the viewpoint of the computer scientist].
AB  - For use on an Apple Macintosh PC, a software packet was developed with the aid of
      which medical students can learn all about primary open-angle glaucoma; at the
      same time, it is also highly suitable for supplementing lectures. The subject is
      subdivided into the three sections anatomy, pathology and clinical picture. All
      the possibilities of computer technology, for example controllable animation,
      video sequences and special graphic effects are utilized. A special lexicon, a
      complex of questions and all the possible cross-references combine to make the
      learning system a very flexible and highly effective learning tool.

PMID- 8142583
TI  - Simulation of arterial drug concentration after intravenous application.
AB  - The aim of this study was to develop a widely applicable model for circulatory
      indicator dispersion which could describe the pharmacokinetics of early drug
      distribution. The model assumes that the substance is injected into the right
      atrium and measured in the aorta. The dilution curve results from the dispersion
      and recirculation of the indicator in the body. The concentration time curve in
      the aorta, r, can be described as r = c0 + g* r, where g is the transport
      function of the body and c0 is the concentration time course, which is measured
      for the first time in the aorta. If the body transport function is known, then
      the aortic dilution curve of a drug can be predicted for different elimination
      rates and injection times. The site of interest can be chosen arbitrarily, i.e.
      the concentration of inflow into the kidney or any other organ can be described.

PMID- 8142584
TI  - [Sedimentation analyser--calibration and testing of a newly developed device for
      recording separation behavior of blood and other dispersed systems].
AB  - A computer-aided sedimentation analyser is described, which can be used for the
      continuous monitoring of the separation of blood and other dispersed systems by
      recording the separation-dependent infrared transmission in the range between 100
      xg to 700 xg. Up to eight samples can be measured simultaneously within a short
      period of time, and only a small amount of suspension is required (15 minutes,
      350 microliters). For centrifugal acceleration more than 100 xg and a haematocrit
      range of between 0.2 and 0.7, the evolution of the height of the plasma column
      (HPC) over time is expressed in non-linear regression form by HPC(t) = HPC
      infinity*(1-e-kt) + c. The separation constant k is influenced by plasma
      viscosity, haematocrit, aggregability and erythrocyte deformability, is directly
      proportional to centrifugal acceleration, and declines in hyperbolic fashion with
      increasing haematocrit between 300 xg and 650 xg. The separation constant is
      closely related to the maximum velocity which, in fact, represents the sensitive
      parameter of separation. Thus, the sedimentation analyser can be applied as an
      alternative to the traditional measurement of erythrocyte sedimentation rate
      according to Westergren.

PMID- 8142585
TI  - Conformational analysis of CCK-B agonists using 1H-NMR and restrained molecular
      dynamics: comparison of biologically active Boc-Trp-(N-Me) Nle-Asp-Phe-NH2 and
      inactive Boc-Trp-(N-Me)Phe-Asp-Phe-NH2.
AB  - The tetrapeptide Boc-Trp-(N-Me)Nle-Asp-Phe-NH2 is a potent CCK-B agonist.
      Replacement in this analogue of the norleucine residue by a phenylalanine, to
      yield Boc-Trp-(N-Me) Phe-Asp-Phe-NH2, led to a 740-fold decrease in affinity
      whereas the same decrease in affinity was not observed in their nonmethylated
      counterparts. In order to ascertain the conformational preferences of these two N
      methylated tetrapeptides, a study by two-dimensional (2D) nmr spectroscopy and
      molecular modeling was undertaken. The solution conformation of the two peptides
      was examined by 1H-nmr in a d6-DMSO/H2O (80:20) mixture. A cis-trans equilibrium,
      induced by N-methylation, was observed for both analogues, and the proton spectra
      of the two rotamers were fully characterized in each case. 1H-1H distance
      constraints, derived from 2D nuclear Overhauser effect spectroscopy and rotating
      frame nuclear Overhauser effect spectroscopy experiments, were used as inputs for
      subsequent restrained molecular dynamics simulations. Comparisons of the nmr and
      molecular modeling data point toward distinct conformational preferences for
      these two peptides with an opposite spatial orientation of the Trp residue, and
      could explain the large difference in their biological activities. Furthermore,
      the tridimensional structure of Boc-Trp-(N-Me)Nle-Asp-Phe-NH2 could serve as a
      model for the design of nonpeptide CCK-B agonists.

PMID- 8142586
TI  - Thermodynamics of cyclophilin catalyzed peptidyl-prolyl isomerization by NMR
      spectroscopy.
AB  - One-dimensional nmr exchange spectroscopy was carried out to determine
      thermodynamic parameters of cyclophilin-induced cis-trans isomerization of
      succinyl-Ala-Phe-Pro-Phe-p-nitroanilide. Rate measurements were possible at
      physiological temperatures. The kc/Km of rat cyclophilin was found to be 12.8 (+/
      0.5) s-1 microM-1 at 37 degrees C, intermediate to previously reported values
      that used a coupled enzyme assay extrapolated to this temperature. Activation
      energies (delta G not equal to) for the uncatalyzed and catalyzed reaction at 37
      degrees C were found to be 19.7 and 17.1 kcal/mol, respectively, and were
      primarily due to an enthalpic barrier.

PMID- 8142587
TI  - CD and Fourier transform ir spectroscopic studies of peptides. II. Detection of
      beta-turns in linear peptides.
AB  - Comparative CD and Fourier transform ir (FTIR) spectroscopic data on N-Boc
      protected linear peptides with or without the (Pro-Gly) beta-turn motif (e.g.,
      Boc-Tyr-Pro-Gly-Phe-Leu-OH and Boc-Tyr-Gly-Pro-Phe-Leu-OH) are reported herein.
      The CD spectra, reflecting both backbone and aromatic contributions, were not
      found to be characteristic of the presence of beta-turns. In the amide I region
      of the FTIR spectra, analyzed by self-deconvolution and curve-fitting methods,
      the beta-turn band showed up between 1639 and 1633 cm-1 in trifluoroethanol (TFE)
      but only for models containing the (Pro-Gly) core. This band was also present in
      the spectra in chloroform but absent in dimethylsulfoxide. These findings, in
      agreement with recent ir data on cyclic models and 3(10)-helical polypeptides and
      proteins in D2O [see S. J. Prestrelski, D. M. Byler, and M. P. Thompson (1991),
      International Journal of Peptide and Protein Research, Vol. 37, pp. 508-512; H.
      H. Mantsch, A. Perczel, M. Hollosi, and G. D. Fasman (1992), FASEB Journal, Vol.
      6, p. A341; H. H. Mantsch, A. Perczel, M. Hollosi, and G. Fasman (1992),
      Biopolymers, Vol. 33, pp. 201-207; S. M. Miick, G. V. Martinez, W. R. Fiori, A.
      P. Todd, and G. L. Millhauser (1992), Nature, Vol. 359, pp. 653-655], suggest
      that the amide I band, with a major contribution from the acceptor C = O of the
      1<--4 intramolecular H bond of beta-turns, appears near or below 1640 cm-1,
      rather than above 1660 cm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142588
TI  - Transient electric birefringence of agarose gels. I. Unidirectional electric
      fields.
AB  - The orientation of agarose gels in pulsed electric fields has been studied by the
      technique of transient electric birefringence. The unidirectional electric fields
      ranged from 2 to 20 V/cm in amplitude and 1 to 100 s in duration, values within
      the range typically used for pulsed field gel electrophoresis (PFGE). Agarose
      gels varying in concentration from 0.3 to 2.0% agarose were studied. The sign of
      the birefringence varied randomly from one gel to another, as described
      previously [J. Stellwagen & N.C. Stellwagen (1989), Nucleic Acids Research, Vol.
      17, 1537-1548]. The sign and amplitude of the birefringence also varied randomly
      at different locations within each gel, indicating that agarose gels contain
      multiple subdomains that orient independently in the electric field. Three or
      four relaxation times of alternating sign were observed during the decay of the
      birefringence. The various relaxation times, which range from 1 to approximately
      120 s, can be attributed to hierarchies of aggregates that orient in different
      directions in the applied electric field. The orienting domains range up to
      approximately 22 microns in size, depending on the pulsing conditions. The
      absolute amplitude of the birefringence of the agarose gels increased
      approximately as the square of the electric field strength. The measured Kerr
      constants are approximately 5 orders of magnitude larger than those observed when
      short, high-voltage pulses are applied to agarose gels. The increase in the Kerr
      constants in the low-voltage regime parallels the increase in the relaxation
      times in low-voltage electric fields. Birefringence saturation curves in both the
      low- and high-voltage regimes can be fitted by theoretical curves for permanent
      dipole orientation. The apparent permanent dipole moment increases approximately
      as the 1.6 power of fiber length, consistent with the presence of overlapping
      agarose helices in the large fiber bundles orienting in low-voltage electric
      fields. The optical factor is approximately independent of fiber length.
      Therefore, the marked increase in the Kerr constants observed in the low-voltage
      regime is due to the large increase in the electrical orientation factor, which
      is due in turn to the increased length of the fiber bundles and domains orienting
      in low-voltage electric fields. Since the size of the fiber bundles and domains
      approximates the size of the DNA molecules being separated by PFGE, the
      orientation of the agarose matrix in the applied electric field may facilitate
      the migration of large DNA molecules during PFGE.

PMID- 8142589
TI  - Discontinuous volume transitions induced by calcium-sodium ion exchange in
      anionic gels and their neurobiological implications.
AB  - Discontinuous volume transitions in poly (acrylic acid) gels were studied by
      determining equilibrium swelling curves of small gel beads immersed in salt
      solutions containing varying concentrations of Ca2+ and Na+. Reversible
      contractions of gel membranes associated with Ca(2+)-Na+ exchange were examined
      using both isometric and isotonic recording devices. A discontinuous change in
      electric conductance was demonstrated in association with Ca(2+)-Na+ exchange in
      gel membranes. These experimental findings provide a sound physicochemical basis
      for elucidating the mechanism of nerve excitation.

PMID- 8142590
TI  - Specificity of trypsin digestion and conformational flexibility at different
      sites of unfolded lysozyme.
AB  - Fourteen tryptic peptides and nine intermediates were identified as products of
      trypsin digestion of reduced and S-3-(trimethylated amino) propylated lysozyme.
      Kinetics of the appearance and disappearance of these products were observed by
      monitoring the peak areas on the chromatogram. In spite of the complicated
      reaction pathways, kinetics of the digestion of proteins and several intermediate
      products show simple decay curves with a single rate constant. In this paper, the
      trypsin susceptibility of the individual cleavage site is defined as a hydrolytic
      rate constant of the susceptible peptide bond in the presence of 10 nM trypsin.
      The cleavage sites of unfolded lysozyme are classified into two groups in terms
      of the trypsin susceptibility: one has a high susceptibility (10-20 h-1) and the
      other a low susceptibility (1.0-2.0 h-1). In the unfolded state of lysozyme, in
      conclusion, the region from residues 15 to 61 has a strong resistance to trypsin
      digestion; on the other hand, the C-terminal half of the polypeptide chain is
      flexible enough to fit into the active site of trypsin. In addition, six kinds of
      pentapeptides were synthesized as analogues of lysozyme fragments including Arg
      14, Arg 21, Lys 33, Arg 45, Arg 61, and Arg 73. Kinetics of tryptic digestion of
      them were observed. Both kcat and KM were determined for these synthetic
      pentapeptides. The susceptibility of each cleavage site in pentapeptides is
      determined and compared with that corresponding in proteins. The susceptibility
      is usually higher when the susceptible peptide bond is included in proteins than
      in pentapeptides, so long as the conformation of peptide chain is flexible.
      However, susceptibilities of a few sites in proteins are lower than those in
      pentapeptides. This means that the peptide chains tend to fold locally to prevent
      trypsin from binding to the sites. It was found that the sites of Arg 21 and Arg
      45 are indeed resistant to trypsin, but the site of Lys 33 is not so much,
      although the hydrolytic rate at Lys 33 itself is extremely slow.

PMID- 8142591
TI  - Monte Carlo and Poisson-Boltzmann calculations of the fraction of counterions
      bound to DNA.
AB  - The counterion density and the condensation region around DNA have been examined
      as functions of both ion size and added-salt concentration using Metropolis Monte
      Carlo (MC) and Poisson-Boltzmann (PB) methods. Two different definitions of the
      "bound" and "free" components of the electrolyte ion atmosphere were used to
      compare these approaches. First, calculation of the ion density in different
      spatial regions around the polyelectrolyte molecule indicates, in agreement with
      previous work, that the PB equation does not predict an invariance of the surface
      concentration of counterions as electrolyte is added to the system. Further, the
      PB equation underestimates the counterion concentration at the DNA surface,
      compared to the MC results, the difference being greatest in the grooves, where
      ionic concentrations are highest. If counterions within a fixed radius of the
      helical axis are considered to be bound, then the fraction of polyelectrolyte
      charge neutralized by counterions would be predicted to increase as the bulk
      electrolyte concentration increases. A second categorization--one in which
      monovalent cations in regions where the average electrostatic potential is less
      than -kT are considered to be bound--provides an informative basis for comparison
      of MC and PB with each other and with counterion-condensation theory. By this
      criterion, PB calculations on the B form of DNA indicate that the amount of bound
      counterion charge per phosphate group is about .67 and is independent of salt
      concentration. A particularly provocative observation is that when this binding
      criterion is used, MC calculations quantitatively reproduce the bound fraction
      predicted by counterion-condensation theory for all-atom models of B-DNA and A
      DNA as well as for charged cylinders of varying linear charge densities. For
      example, for B-DNA and A-DNA, the fractions of phosphate groups neutralized by 2
      A hard sphere counterions are 0.768 and .817, respectively. For theoretical
      studies, the radius enclosing the region in which the electrostatic potential is
      calculated to be less than -kT is advocated as a more suitable binding or
      condensation radius than that enclosing the fraction of counterions given by (1 -
      epsilon-1). A comparison of radii calculated using both of these definitions is
      presented.

PMID- 8142592
TI  - Thermodynamic strategies for stabilizing intermediate states of proteins.
AB  - This paper presents three theorems pertaining to thermodynamic properties of the
      intermediate (e.g., molten globule) state of proteins exhibiting such a
      conformation in the presence of GuHCl or urea. The theorems are proved for the
      three-state case using the denaturant binding model and the linear extrapolation
      model; their utility is illustrated via applications to examples in the
      literature. Theorem One states that the denaturant activity that maximizes the
      population of a partly folded conformation is at any temperature independent of
      the Gibbs free energy difference between the intermediate and native states. This
      result holds for both models of protein-denaturant interaction. The second
      theorem claims that the population maximum is independent of the denaturant
      association constant for the denaturant binding model. Theorem Three, which also
      applies to both models considered here, states that at the temperatures
      corresponding to the extrema in the population of the intermediate, the enthalpy
      change of the intermediate is equal to the excess enthalpy function, an
      experimentally accessible quantity. In the absence of denaturant, the enthalpy
      change of the intermediate state at the population extrema can be written as a
      function of the thermodynamic parameters of the unfolded state alone. These
      results, which can be applied to systems of any number of states under certain
      conditions, should aid in the optimization of conditions employed for
      experimental studies of partly organized states of proteins.

PMID- 8142593
TI  - Bioactive peptides: solid state, solution and molecular dynamics studies of a
      cyclolinopeptide A-related cystinyl cyclopentapeptide.
AB  - The conformational analysis of [sequence: see text] the disulphide cyclopeptide
      related cyclolinopeptide A, has been carried out by solid state methods using x
      ray diffraction techniques, in solution by nmr, CD, ir spectroscopies, and by
      molecular dynamics (MD) analysis. The structure of the monoclinic form, obtained
      from ethanol (a = 11.303(2) A, b = 14.467(8) A, c = 12.355(2) A, beta(degree) =
      109.40(1), space group P2(1), Z = 2) presents two transannular H bonds with the
      formation of one type VIa beta-turn involving the C = O of the urethane moiety
      and the Phe3 NH, and an intramolecular H bond between the C = O of urethane group
      and the Phe4 NH. In the solid state all the peptide bonds are in the trans
      configuration with the exception of a cis peptide bond occurring between the Cys1
      and Pro2 residues; the linkage S-S assumes right-handed chirality. The
      conformational study in solution by nmr spectroscopy indicates that the peptide
      is very flexible and that some conformer families are present at room temperature
      both in polar and apolar solvents. CD studies confirm that this cyclic system
      tends to give rise to a complex mixture of quasi-isoenergetic conformations,
      favored by the flexibility of the disulphide bridge and by the isomerism of the
      Xxx-Pro bond. MD studies carried out in vacuo and in solution shows that the
      structure determined by solid state represents a energy minimum. All hydrogen
      bonds found in the crystalline state are correctly reproduced in vacuo and in
      solution simulations.

PMID- 8142594
TI  - Cytokines and cytokine receptors in health and disease. A summary of the National
      Heart, Lung and Blood Institute Frontiers in Basic Sciences Symposium, December 2
      3, 1992.

PMID- 8142595
TI  - Interleukin 1 receptor antagonist production in human monocytes is induced by IL
      1 alpha, IL-3, IL-4 and GM-CSF.
AB  - Interleukin 1 receptor antagonist (IL-1ra) is induced in monocytes stimulated
      with lipopolysaccharide (LPS) or cultured on adherent immunoglobulin G (IgG). We
      examined the effects of various cytokines on monocyte IL-1ra protein production
      and compared it to IL-1 beta, which is regulated differently. IL-3 and GM-CSF
      induced near equivalent amounts of IL-1ra protein as does LPS. IL-1 alpha and IL
      4 were weaker inducers. IL-3 and GM-CSF did not affect LPS or IgG induction of IL
      1ra or LPS-induced IL-1 beta. However, our data confirmed that IL-4 up-regulated
      LPS-induced IL-1ra and down-regulated LPS-induced IL-1 beta. The kinetics of IL
      1ra production by monocytes varied between stimulation with adherent IgG and
      cytokines or LPS. Cells cultured on adherent IgG exhibited a higher level of and
      more prolonged IL-1ra production. Relative IL-1ra mRNA levels after 8 h were in
      the order: adherent IgG > LPS or GM-CSF > IL-1 alpha, IL-3 or IL-4. The following
      cytokines failed to induce IL-1ra production: IL-2, IL-6, G-CSF, M-CSF, IFN
      gamma, TGF beta 1, TGF beta 2, TNF alpha, acidic and basic FGF, PDGF and EGF.
      These results suggest that IL-1 alpha, IL-3, IL-4 and GM-CSF may play important
      roles in regulating monocyte IL-1ra production and that different mechanisms may
      be involved in induction of IL-1ra by adherent IgG in comparison to LPS or other
      cytokines.

PMID- 8142596
TI  - Comparison of IL-1 alpha effectiveness in activating murine pre-B and T cell
      lines.
AB  - Interleukin-1 (IL-1) is a potent agent that induces a wide range of biological
      effects. The action of IL-1 is mediated by surface IL-1 receptors (IL-1R). Two
      types of IL-1 receptors have been identified in lymphocytes. In this study we
      examined activity of IL-1 alpha in two murine lymphocyte lines that express
      different types of IL-1 receptors. The T lymphoid cell line EL-4 6.1 C10
      expresses type I IL-1R that mediates IL-1 alpha-induced IL-2 gene expression and
      secretion of IL-2. The pre-B lymphoid cell line 70Z/3 was previously shown to
      express type II IL-1R and responds to IL-1 alpha by expressing immunoglobulin
      kappa light chain mRNA and increased levels of surface IgM. We found that IL-1
      alpha was as potent in inducing IgM expression in 70Z/3 cells as it was in
      inducing IL-2 secretion in EL-4 6.1 C10 cells. Likewise, the IL-1 alpha
      concentration sufficient to trigger kappa light chain gene expression in 70Z/3
      cells was similar to the concentration of IL-1 alpha sufficient to trigger IL-2
      gene expression in EL-4 6.1 C10. In both cell lines, IL-1 alpha activated NF
      kappa B-like DNA-binding activity but in EL-4 6.1 C10 cells the IL-1 alpha
      concentration sufficient to induce NF-kappa B response was 1000-fold lower than
      in 70Z/3 cells. Monoclonal antibody, mAb M15, to the type I IL-1R blocked IL-1
      induced responses in EL-4 6.1 C10 cells. Surprisingly mAb M15 also blocked IL-1
      action in 70Z/3 cells, even though these cells predominantly express type II IL
      1R. 15% of the total IL-1 binding sites in 70Z/3 cells were recognized by mAb
      M15. Human IL-1 receptor antagonist (IL-1ra), which binds to the natural murine
      type I but not the type II IL-1R, blocked IL-1 alpha responses in EL-4 6.1 C10
      and 70Z/3 cells. Although at low levels, Northern blot analysis confirmed that
      70Z/3 cells express low levels of type I IL-1R mRNA. Taken together, these
      results suggest that type I IL-1R are expressed and transduce IL-1 signals in
      both 70Z/3 and El-4 6.1 C10 cells.

PMID- 8142597
TI  - Specific binding of interleukin 1 (IL-1) beta and IL-1 receptor antagonist (IL
      1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor
      type I.
AB  - Molecules that bind recombinant interleukin 1 (rIL-1) beta and rIL-1 receptor
      antagonist (rIL-1ra) with high affinity were detected in sera of healthy
      individuals. rIL-1 beta bound with dissociation constants in the nanomolar range,
      and the serum binding capacity was 40-50 ng/ml. rIL-1ra bound with 30 times
      higher affinity, and the serum binding capacity was 0.7-1 ng/ml. Rabbit
      antibodies against the recombinant-derived extracellular part of human IL-1
      receptor type I (rsIL-1RI) selectively inhibited the binding of 125I-rIL-1ra to
      the serum factor(s). Almost 70% of the high-affinity IL-1ra-binding capacity was
      recovered after immunosorption with these antibodies. Binding of 125I-rIL-1ra to
      rsIL-1RI was blocked by rIL-1 alpha and by rIL-1 beta. In contrast, the purified
      rIL-1ra-binding factor (IL-1raBF) failed to bind rIL-1 alpha and rIL-1 beta. Gel
      filtration chromatography indicated a 1:1 binding of rIL-1 beta and rIL-1ra to
      their respective serum factors. The apparent molecular size of both serum factors
      was 70-80 kDa. Using SDS-PAGE and autoradiography, IL-1raBF had a molecular size
      of 60 kDa. We conclude that IL-1raBF, a serum factor which selectively and with
      high affinity binds IL-1ra (Kd = 70 pM), is related to or identical with a
      soluble form of IL-1RI. If upregulated during disease, IL-1raBF may constitute
      yet another level of natural regulation of IL-1 bioactivities.

PMID- 8142598
TI  - Cachectin/TNF-mediated lactate production in cultured myocytes is linked to
      activation of a futile substrate cycle.
AB  - The cytokine cachectin/TNF induces a rapid increase in lactate production and in
      glucose metabolism in L6 myocytes in culture; glucose uptake was maximal after 17
      h, while elevated glucose utilization and lactate production persisted for up to
      32 h. These increases are suggestive of increased glycolytic activity, and were
      associated with a 10% decrease in cellular oxygen consumption and a comparable
      decrease in the production of 14C-labelled CO2 from 14C-labelled glucose. This
      decrease in aerobic metabolism, however, could account for only a small fraction
      of the energetic requirement for increased glycolytic activity. Furthermore,
      maximal stimulation of pyruvate dehydrogenase (PDH) by dichloroacetate (DCA)
      treatment in conjunction with cachectin/TNF abolished lactate production, but
      increased glucose uptake persisted. Taken together, this suggests that the
      primary effect of cachectin/TNF on myocyte carbohydrate metabolism is to increase
      glycolysis. Correspondingly, we postulated that cachectin/TNF must activate one
      or more ATP-depleting cellular processes to account for the lack of feed-back
      inhibition on glycolysis by the ATP produced. This led to the identification of a
      futile substrate cycle between fructose 6-phosphate and fructose 1,6-bisphosphate
      as a novel energy sink that is activated by cachectin/TNF. Cachectin/TNF
      treatment led to increased activity of both phosphofructokinase (PFK) and
      fructose bisphosphate phosphatase (FBP) in myocytes in culture, detectable after
      1 h of incubation and persisting for up to 16 h. The possible role of
      cachectin/TNF-mediated futile substrate cycling in increased glycolytic activity,
      increased energy expenditure, heat production and tissue wasting during bacterial
      infections is discussed.

PMID- 8142599
TI  - High levels of portal TNF-alpha during abdominal aortic surgery in man.
AB  - During shock or multiple organ dysfunction syndrome, translocation of bacteria
      and/or lipopolysaccharide (LPS) from the ischaemic gut might occur and could
      explain the excess of cytokine production detectable in plasma. To test this
      hypothesis, we studied a model of mild gut ischaemia due to bowel manipulation
      and aortic clamping in patients undergoing abdominal aortic surgery (n = 14). Per
      operative levels of LPS and cytokines were measured before clamping and after
      reperfusion, and compared in systemic and portal blood. Systemic levels of LPS
      and cytokines were measured in a control group of patients undergoing internal
      carotid surgery (n = 7). Portal LPS was detectable (i.e., > 12 pg/ml) in 36% of
      the patients undergoing aortic surgery after bowel manipulation, and in 71% after
      clamp release. Similar levels of LPS were observed in portal and systemic blood
      after clamp release. Circulating tumour necrosis factor alpha (TNF-alpha) was
      observed in all patients undergoing aortic surgery. Levels of portal TNF-alpha
      were higher than those in systemic blood after bowel manipulation as well as
      after reperfusion (P = 0.02 and 0.007, respectively). LPS was never detected in
      control patients and TNF-alpha was detectable in only two out of seven patients.
      Mean levels of IL-6 were similar in the two groups, with a peak on the day
      following surgery, confirming that circulating IL-6 is associated with any
      surgical procedures. Our data indicate that bowel manipulation, aortic clamping
      and reperfusion lead to similar levels of portal and systemic circulating
      LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142600
TI  - Increased fibrinogen synthesis in mice during the acute phase response: co
      operative interaction of interleukin 1, interleukin 6, and interleukin 1 receptor
      antagonist.
AB  - Interleukin 6 (IL-6) stimulates fibrinogen (Fg) gene expression both in vivo and
      in vitro; while interleukin 1 (IL-1) paradoxically stimulates in vivo, yet
      inhibits in vitro, Fg synthesis. The naturally occurring interleukin 1 receptor
      antagonist (IL-1ra) and passive immunization with anti-IL-6 antiserum were used
      to study the in vivo mechanism of action of IL-1 on Fg gene expression. Changes
      in plasma Fg and hepatic Fg mRNA concentrations were measured following
      administration of exogenous IL-1ra together with IL-6 or IL-1 to CD2F1 mice. Our
      results suggest that in vivo, IL-1 per se inhibits Fg production since when IL
      1ra was co-administered with IL-6, greater concentrations of Fg were observed
      than when IL-6 was administered alone. The data suggest that IL-1 stimulates Fg
      production through intermediate production of IL-6, since stimulation was
      abrogated when either IL-1ra or anti-IL-6 antiserum was co-administered with IL
      1. An in vivo role for IL-1ra in the stimulation of Fg by IL-1 was supported by
      the observation that within 1 h of IL-1 administration to mice, IL-1ra mRNA was
      detectable in liver. It appears that IL-1, an early mediator of inflammation,
      inhibits constitutive expression of Fg genes and stimulates the IL-1ra and IL-6
      genes. The inhibitory effect of IL-1 is reversed by endogenous IL-1ra and by the
      direct stimulation of Fg gene expression by IL-6.

PMID- 8142601
TI  - Protective effect of natural TNF-binding protein on human TNF-induced toxicity in
      mice.
AB  - The in vivo protective effect of urinary TNF-binding protein (uTBP) on acute TNF
      induced lesions and lethality was assessed in BALB/c mice. Two animal models, the
      local Shwartzman reaction and galactosamine (GaLN) induced TNF sensitization,
      were used. In the former, local cutaneous haemorrhagic necrosis induced by 10
      micrograms of recombinant human TNF alpha (r-hTNF) was prevented with iv doses of
      uTPB as low as 1 microgram when administered concomitantly or 10 micrograms when
      injected intravenously 60 min before or 30 min after the lesion eliciting-dose of
      r-hTNF. In the latter model, injection of 1 microgram or r-hTNF caused the death
      of all mice within 36 h. Either 100 or 250 micrograms of uTBP given intravenously
      simultaneously with r-hTNF/GaLN totally prevented this mortality. In contrast to
      anti-human TNF monoclonal antibodies, these very same doses of uTBP significantly
      protected mice even when injected after the lethal r-hTNF dose. These data
      confirm in relevant in vivo pathological models the TNF inhibiting capacity of
      the natural soluble TNF receptor I.

PMID- 8142602
TI  - Mechanisms of paraneoplastic syndromes of colon-26: involvement of interleukin 6
      in hypercalcemia.
AB  - The precise mechanisms responsible for increased calcium levels in patients with
      cancer are not fully understood. In a recent study, the participation of
      interleukin (IL)-6 as an important mediator of key parameters of cancer cachexia
      in the colon-26 adenocarcinoma was reported. Here, we show that in addition to
      cachexia, C-26 tumour bearing mice also develop hypercalcemia. Treatment of these
      mice with 5' deoxyfluorouridine significantly reduces tumour size and inhibits
      both hypercalcemia, cachexia, and elevated serum IL-6. Moreover, monoclonal
      antibody to mouse IL-6 prevents both the cachexia and the hypercalcemia and
      reduces serum IL-6 levels in C-26 tumour bearing hosts. The administration of a
      bisphosphonate compound (Clodronate) reverses the hypercalcemia but has no effect
      on tumour burden, serum IL-6 levels, or wasting. We conclude that tumour-derived
      IL-6 plays a role in the pathogenesis of the C-26 associated hypercalcemia, and
      that the increase of serum calcium does not by itself mediate cachexia.

PMID- 8142603
TI  - Qualitative and quantitative studies of cytokines synthesized and secreted by non
      human primate peripheral blood mononuclear cells.
AB  - Non-human primates are being utilized in a variety of pre-clinical studies,
      including those involved with mechanisms of organ transplant rejection and those
      being used as models to test the efficacy of vaccines against a variety of
      infectious diseases, most notably AIDS. These studies clearly involve
      immunological effector mechanisms, which include the interaction between T cells,
      B cells, monocytes, and cytokines that regulate these interactions. However,
      there is very little known about assays and quantitation of cytokines from non
      human primates. In attempts to address this issue, bioassays, commercially
      available EIA kits, and primer pairs and probes specific for human cytokines were
      evaluated for their ability to detect and quantitate the non-human primate
      homologues. Data suggest that although the EIA kits that were evaluated for human
      IL-1 alpha, IFN-gamma, and TNF-beta failed, the EIA kits for IL-1 beta, IL-2, IL
      4, IL-6, and TNF-alpha, the bioassays and RT-PCR assays for each of the cytokines
      were successful in detection and most likely quantitation of the non-human
      primate cytokine homologues. These assays will greatly facilitate future studies
      on the role of cytokines in these non-human primate studies.

PMID- 8142604
TI  - Characterization of a new IL-6-dependent human B-lymphoma cell line in long term
      culture.
AB  - We have established a cell line (DS-1) of B-cell lineage in long-term culture. It
      was derived from an immunodeficient patient with intestinal lymphangiectasia and
      lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The
      cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(
      ). Cell proliferation was poor in medium and exhibited an eight-fold, dose
      dependent increase of proliferation in response to rIL-6 of human but not murine
      origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced
      by rIL-6. While constitutive production of IL-6 was not detected by bioassay
      using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was
      detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation
      of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%)
      and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity
      IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by
      radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine
      IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies
      arising in patients with AIDS and other immunodeficiency diseases. Despite
      constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon
      exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell
      line may also facilitate development of strategies for diagnosis and treatment of
      B-cell lymphomas in immunocompromised patients.

PMID- 8142605
TI  - Modulation by bryostatin 1 of the in vitro radioprotective effects of the GM
      CSF/IL-3 fusion protein, PIXY 321, on normal human myeloid progenitors.
AB  - We have examined the effect of the macrocyclic lactone PK-C activator, bryostatin
      1, on the in vitro radioprotective capacity of the GM-CSF/IL-3 fusion protein,
      PIXY 321, toward normal committed myeloid progenitors (day 14 CFU-GM).
      Preincubation of CD 34+ cells for 24 h with 10 ng/ml PIXY 321 exerted significant
      radioprotective effects on these progenitors, (D = 1.403 vs 0.715 for controls),
      which were at least as great as those previously reported for higher
      concentrations (e.g., 50 ng/ml) or rGM-CSF. In contrast to the results of earlier
      studies involving rGM-CSF, preincubation of cells with both PIXY 321 and 10 nM
      bryostatin 1 did not lead to an increase in radioprotective effect when the total
      number of day 14 colonies was assessed. However, combinations of PIXY 321 and
      bryostatin 1 (or the tumour-promoting PK-C activator, PDBu) significantly
      increased the relative percentage and absolute number of surviving non
      eosinophilic colonies (e.g., pure neutrophil, pure monocyte-macrophage, or mixed
      neutrophil-macrophage) at each radiation dose level. A similar pattern of
      response was noted in cells irradiated without a preconditioning interval, and in
      cells exposed to divided radiation doses. These results indicate that the GM
      CSF/IL-3 fusion protein PIXY 321 exhibits significant in vitro radioprotective
      effects toward normal human bone marrow myeloid progenitors, and that co
      administration of PK-C activators such as bryostatin 1 of PDBu selectively
      augments the radioprotective capacity of this hybrid cytokine toward non
      eosinophilic elements.

PMID- 8142606
TI  - Effects of recombinant human cytokines on mitogen-induced bovine peripheral blood
      mononuclear cell proliferation.
AB  - The effects of interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL
      5, IL-6, IL-7, IL-8, and insulin growth factor-1 (IGF-1) on proliferation of
      mitogen-stimulated bovine peripheral blood mononuclear cells (PBMC) were
      determined. Four concentrations of each cytokine were incubated 48 or 96 h with
      PBMC alone or with PBMC and three concentrations of three different mitogens. The
      mitogens included concanavalin A (Con A) phytohemagglutinin (PHA), and
      Escherichia coli 055:B5 lipopolysaccharide (LPS). Proliferation of unstimulated
      PBMC was not affected by IL-1 alpha, IL-1 beta, IL-3, IL-5, IL-6, IL-8, and IGF-1
      whereas IL-2, IL-4, and IL-7 increased proliferation. Incubation of PBMC with Con
      A plus IL-1 alpha, IL-2, IL-4, IL-7 or IL-8 increased proliferation when compared
      to PBMC that were incubated with either Con A or the cytokine alone. Interleukin
      1 beta, IL-3, IL-5, IL-6 and IGF-1 did not influence proliferation of Con A
      stimulated PBMC. Proliferation of PHA-stimulated PBMC was increased when PBMC
      were cultured with IL-2, IL-4 or IL-7, but not when cultured with IL-1 alpha, IL
      1 beta, IL-3, IL-5, IL-6, IL-8 or IGF-1. Similar results occurred with LPS
      stimulated PBMC in that proliferation induced by LPS was enhanced by IL-2 or IL
      7, but not by any of the other cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142607
TI  - Recombinant expression of rat and human Gro proteins in Escherichia coli.
AB  - A full-length rat gro cDNA containing the signal sequence was inserted to a
      plasmid/phage vector pTD-lacs which had the Escherichia coli alkaline phosphatase
      leader sequence down-stream of the lac promoter. After removal of the gro signal
      sequence by site-directed mutagenesis, the vector was introduced to E. coli
      JM109. The cells grown in the presence of isopropyl beta-D-thiogalactopyranoside
      were found to contain the recombinant mature rat Gro protein in the periplasmic
      space. The protein was released from the cells by osmotic shock, and could be
      purified to homogeneity from the periplasmic fluid by a single-step procedure
      using reverse phase high performance liquid chromatography. By similar
      procedures, recombinant human Gro alpha could be obtained. In each case, about 10
      mg of purified cytokine were obtained from 1 litre of bacterial culture.

PMID- 8142608
TI  - Cross-linking of human neutrophil surface proteins to iodinated interleukin 8 or
      neutrophil activating peptide-2 results in at least four separable proteins.
AB  - The human neutrophil activating peptides-1 and -2 (NAP-1/IL-8, NAP-2) are two
      structurally and functionally related members of the chemokine cytokine family.
      They are chemoattractants and activators of neutrophils and exert their effects
      by binding to specific receptors which are expressed on responsive cells. Two
      closely related IL-8 receptors of neutrophils have been characterized recently by
      molecular cloning. We show here that NAP-1/IL-8 and NAP-2 can be cross-linked to
      at least four protein bands from human neutrophil surfaces with apparent
      molecular masses of 55, 65, 71 and 81 kDa. The two cross-linked proteins with
      lower masses were associated with high, the two with the higher masses with low
      affinity binding of NAP-2, NAP-1/IL-8 was bound to all bands with high affinity.
      NAP-1/IL-8 and NAP-2 could also be cross-linked to form dimers when bound to
      cells and in solution. Our results show that more than two NAP-1/IL-8 receptors,
      or more than two forms of the known receptors exist. Alternatively, the four
      protein bands can be explained by cross-linking of ligand monomers and dimers,
      respectively, to the known receptors of neutrophils.

PMID- 8142609
TI  - Expression of monocyte chemotactic and activating factor (MCAF) in skin related
      cells. A comparative study.
AB  - A significant proportion of the infiltrating cells in several inflammatory skin
      diseases, including psoriasis and allergic contact dermatitis, are monocytes.
      Additionally, it is known that the cytokine monocyte chemotactic and activating
      factor (MCAF) can be produced by several cell types present in the skin,
      suggesting a significant role for MCAF in the accumulation of monocytes during
      immunological and inflammatory skin reactions. We have recently developed a
      precise method for quantification of the amount of a specific mRNA species in a
      given sample and have used this technique to compare specific MCAF mRNA amounts
      in cultures of human keratinocytes, dermal fibroblasts, endothelial cells, and
      monocytes, after stimulation with interleukin 1 alpha (IL-1 alpha) for 6 h.
      Endothelial cells produced very high, monocytes and fibroblasts intermediate, and
      keratinocytes low amounts of MCAF mRNA. We have also performed time course
      studies of MCAF mRNA levels in the four cell types. Our findings suggest that the
      regulation of MCAF mRNA expression in these cells parallels the regulation of the
      lymphocyte and neutrophil chemotactic factor interleukin 8.

PMID- 8142611
TI  - Mouse polyomavirus mediated effects on the infected cell membrane studied by
      dielectric spectroscopy.
AB  - The effect of polyomavirus on the infected cell has been investigated by
      dielectric spectroscopy. This technique has a great potential in the study of the
      ion transport properties of the cell membrane. The results presented in this
      communication suggest a correlation between progression of the viral infection
      and dielectric features of the infected cell plasma membrane.

PMID- 8142610
TI  - The pneumotoxicant paraquat induces IL-8 mRNA in human mononuclear cells and
      pulmonary epithelial cells.
AB  - Paraquat (PQ) is a herbicide which is highly pneumotoxic by generating reactive
      oxygen intermediates (ROI). Pro-inflammatory cytokines, particularly IL-1 and
      TNF, have been implicated in some ROI-mediated pathologies, including bleomycin
      toxicity and ischaemia/reperfusion injury. We have studied the effect of PQ on
      the expression of the neutrophil chemotactic cytokine, IL-8, by human peripheral
      blood mononuclear cells (PBMC). While almost no IL-8 mRNA was detected in
      unstimulated cells, PQ (100 microM) induced high mRNA expression with a maximum
      at 24 h of incubation. While PQ did stimulate the appearance of IL-8 mRNA, no
      significant production of IL-8 protein was detected. However, PQ potentiated the
      production of IL-8 in the presence of 1 ng/ml of endotoxin (lipopolysaccharide,
      LPS). This was paralleled by an increased production of chemotactic activity for
      neutrophils, indicating that the IL-8 was actually bioactive. Stimulation of IL-8
      mRNA by PQ was suppressed by IL-4 and by free radical scavengers
      (dimethylsulfoxide, mannitol). Increased IL-8 expression by PQ was also observed
      in the human pulmonary epithelial cell line A549 indicating that the effect of PQ
      was not specific for PBMC. These findings suggest that IL-8 might be involved in
      the pulmonary effects of PQ and that its production might be stimulated following
      an oxidative insult, and might clarify the pathogenetic mechanisms of adult
      respiratory distress syndrome (ARDS) or oxidant-induced pulmonary fibrosis.

PMID- 8142612
TI  - Further evidence for an active site polypeptide of galactosyl transferase.
AB  - In a previous report it was shown that galactosyl transferase activity after
      blotting from acrylamide gel was present in a molecular weight range of less than
      14 kDa, in Triton X-100 (1). Molecular sieve chromatography on Superose 12, in
      the presence of Triton X-100, gave the same result. The low molecular weight
      activity peak was eluted together with peptides as a part of the covalent
      structure of the enzyme or as absolutely requires effectors. Peptide mapping
      showed a new poly-lysine-like peptide and a new hydrophobic peptide in this low
      molecular weight activity peak as effectors of the enzyme inside its hydrophobic
      environment.

PMID- 8142614
TI  - Myosin light chain kinase expression during smooth muscle development.
AB  - The expression of smooth muscle myosin light chain kinase (MLCK) was investigated
      during chicken gizzard development. The molecular weight and the antigenic
      properties of MLCK did not change during development. The use of anion exchange
      high performance liquid chromatography (HPLC) enabled us to distinguish between
      MLCKs from post-hatched and adult chickens. A partial amino acid sequence
      determination of 4-day-old gizzard MLCK failed to disclose differences in the
      primary sequences of the two proteins. The results suggest that MLCK has the same
      primary sequence in all stages of gizzard development, although charge variants
      due to post-translational modifications may exist.

PMID- 8142613
TI  - Surgically induced uremia in rats. I: Effect on bone strength and metabolism.
AB  - During the course of chronic renal failure (CRF) in man, renal osteodystrophy
      (osteitis fibrosa and/or osteomalacia) gradually develops. The present study
      aimed to establish a similar type of CRF leading to renal osteodystrophy in rats.
      During progressive CRF development over 225 days after 5/6 nephrectomy, the
      following serum variables were measured: creatinine, immunoreactive parathyroid
      hormone (iPTH), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a25-hydroxyvitamin D3,
      (25(OH)D3), alkaline phosphatase, albumin, phosphate, urea nitrogen, total
      calcium, and other blood electrolytes. Subsequent to sacrifice, mechanical
      properties of the rat femur, bone histomorphometry (osteoid and eroded surfaces)
      and bone contents of calcium, phosphate and hydroxyproline were also examined.
      Serum creatinine in rats with CRF gradually escalated by some 70%, while
      circulating 1,25(OH)2D3 was reduced beneath detection level. Total plasma calcium
      and phosphate concentrations were, however, almost unchanged indicating that PTH
      induced bone remodeling due to moderate hyperparathyroidism sustained calcium
      homeostasis. Alkaline phosphatase levels were reduced by some 50%, which reflects
      chronically impeded bone formation. Bone histomorphometry assessment revealed
      substantial elevation of resorption with moderate accompanying fibrosis in about
      70% of afflicted animals. Bone calcium, phosphate and hydroxypyrroline contents
      remained unaltered. However, hydroxyproline/calcium ratio was marginally reduced.
      These results, together with altered mechanical bending stress characteristics
      and diminished diaphysis cross section area, confirm development of mixed bone
      lesions in the uremic animals. Our results are compatible with the early
      development of CRF in man. The established rat model is therefore useful in
      elucidating the precipitation and early treatment of renal osteodystrophy in
      humans.

PMID- 8142615
TI  - Insulin-like growth factor I enhances the formation of type I collagen in
      hydrocortisone-treated human osteoblasts.
AB  - We have studied the effect of insulin-like growth factor I (IGF-I) on the
      formation of osteocalcin and type I collagen in isolated human osteoblasts. IGF-I
      at and above 0.1 nM stimulated the formation of type I collagen as measured by
      the type I procollagen carboxyterminal peptide (PICP), in human osteoblasts,
      incubated for 72 hrs in serum free conditions. The secretion of osteocalcin was
      not affected by IGF-I while 1,25(OH)2vitamin D3 significantly enhanced the
      formation of osteocalcin. When human osteoblast-like cells were incubated with
      hydrocortisone (1 microM), a significant decrease in the release of both PICP and
      osteocalcin was seen. Addition of IGF-I to human osteoblasts also treated with
      hydrocortisone normalized the PICP-formation but did not affect the suppressed
      osteocalcin-formation. These data indicate that IGF-I reverses selective effects
      of hydrocortisone on bone.

PMID- 8142616
TI  - Amplification and expression of the TGF-alpha, EGF receptor and c-myc genes in
      four human oesophageal squamous cell carcinoma lines.
AB  - We have previously shown that four human oesophageal squamous cell carcinoma
      (SCC) cell lines secrete significant quantities of transforming growth factor
      alpha (TGF-alpha) in vitro. Three of these lines are known to produce
      supernumerary low-affinity epidermal growth factor receptors (EGF-Rs). Using an
      125I-EGF competitive binding assay and Scatchard analysis, we show that the
      fourth also overproduces low-affinity receptors. According to slot blot DNA
      analyses, the secretion of high levels of TGF-alpha is not associated with
      amplification of the TGF-alpha gene, and hyperproduction of the EGF-R is
      correlated with receptor gene amplification. Western blot analyses show that the
      c-Myc protein is overexpressed in two of the cell lines; and Southern and
      Northern blot analyses indicate that this overexpression occurs independently of
      c-myc gene amplification. Our results are consistent with an autocrine role for
      TGF-alpha and EGF-R in oesophageal carcinogenesis and support the possibility
      that c-myc overexpression may be required for the in vivo tumourigenicity of
      cells that produce high levels of TGF-alpha and the EGF-R.

PMID- 8142617
TI  - Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death.
AB  - The maintenance of homeostasis in normal tissues reflects a balance between cell
      proliferation and cell death. The importance of both positive and negative
      regulators of cell growth has been well documented in neoplasia. Bcl-2 argues for
      the existence of a new category of oncogenes, regulators of cell death. The bcl-2
      gene was identified at the chromosomal breakpoint of t(14; 18) bearing B cell
      lymphomas. Bcl-2 has proved to be unique among protooncogenes in blocking
      programmed cell death rather than promoting proliferation. In adults, bcl-2 is
      topographically restricted to progenitor cells and longlived cells but is much
      more widespread in the developing embryo. Transgenic mice that overexpress bcl-2
      in the B cell lineage demonstrate extended cell survival, and progress to high
      grade lymphomas. Bcl-2 has been localized to mitochondria, endoplasmic reticulum
      and nuclear membranes, also the sites of reactive oxygen species generation. Bcl
      2 does not appear to influence the generation of oxygen free radicals but does
      prevent oxidative damage to cellular constituents including lipid membranes. Bcl
      2 deficient mice complete embryonic development and display relatively normal
      haematopoietic differentiation but undergo fulminant lymphoid apoptosis of thymus
      and spleen. Moreover, they demonstrate two potentially oxidation related
      pathologies: polycystic kidney disease and hair hypopigmentation. A family of bcl
      2 related genes is emerging that includes Bax, a conserved homolog that
      heterodimerizes in vivo with bcl-2. A pre-set ratio of Bcl-2/Bax appears to
      determine the survival or death of cells following an apoptotic stimulus.

PMID- 8142618
TI  - Chromosomal translocations in leukaemia.
AB  - Many haematologic malignancies carry characteristic chromosomal translocations,
      which are thought to play an important role in the pathogenesis of these tumours.
      The t(8; 14) translocation in Burkitt's lymphoma was one of the first
      characterized at the molecular level. In this translocation the c-myc oncogene at
      chromosome 8q24 becomes deregulated by enhancer elements of the immunoglobulin
      heavy chain locus at chromosome 14q32 leading to a very aggressive B cell
      malignancy. Translocations involving an overexpressed c-myc gene are also found
      in AIDS-associated lymphoma or in T cell leukaemias, or they develop during
      tumour progression of a low grade B cell malignancy into a high grade B cell
      tumour in an additional cytogenetic change. A different mechanism of oncogene
      activation in a leukaemia specific chromosomal abnormality is found for CML,
      where c-abl sequences are fused into the bcr locus, or in the t(4; 11) of acute
      childhood leukaemia involving the recently identified ALL-1 gene at chromosome
      11q23 resulting in a malfunctioning, structurally altered oncogene. Thus, in the
      past molecular and somatic cell genetic studies have clarified many details in
      aetiology and progression of leukaemias and lymphomas which are useful for
      applications in clinical diagnostics, and which in the future will be helpful in
      designing a therapy based on a molecular understanding.

PMID- 8142619
TI  - TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T
      cell acute leukaemia.
AB  - TAL1 gene rearrangement is the most common genetic defect associated with T cell
      acute lymphoblastic leukaemia (T-ALL). Tumour-specific rearrangements of TAL1
      arise as a result of either chromosome translocation or local DNA recombination.
      TAL1 gene products possess the basic helix-loop-helix (bHLH) motif, a DNA-binding
      domain common to several known transcription factors. The bHLH domain of TAL1 is
      especially homologous to those encoded by TAL2 and LYL1, distinct genes that were
      also identified on the basis of chromosomal rearrangement in T-ALL. Thus, TAL1,
      TAL2 and LYL1 constitute a unique family of bHLH proteins, each of which is a
      potential mediator of T cell leukaemogenesis.

PMID- 8142620
TI  - LIM domain proteins in leukaemia and development.
AB  - T cell acute leukaemias involve a number of different classes of oncogenes. A
      group of such genes is the RBTN family located on chromosomes 11 and 12. Two
      members of this family, RBTN1/Ttg-1 and RBTN2/Ttg-2, are located near recurring T
      cell acute lymphocytic leukaemia-associated translocations. Chromosomal
      translocations to both RBTN1/Ttg-1 and RBTN2/Ttg-2 involve T cell receptor (TCR)
      genes as result of an erroneous V(D)J joining process. RBTN1/Ttg-1 and RBTN2/Ttg
      2 encode related proteins consisting of two cysteine-rich regions called LIM
      domains. The fact that LIM domains can be found with or without associated
      homeodomain led to the suggestion that the LIM domains may function as regulators
      of transcription, and that alterations of transcription networks, after
      chromosomal translocations, lead to leukaemia. This is a common feature that has
      been noted in the activation of transcription factors with a variety of
      structural motifs that include the basic helix-loop-helix motif and the
      homeodomain in leukaemias.

PMID- 8142621
TI  - Acute promyelocytic leukaemia and the t(15;17) translocation.
AB  - Acute promyelocytic leukaemia (APL) is a rare acute myeloid leukaemia
      characterized by a distinctive coagulopathy, the differentiation of promyelocytes
      in response to all-trans retinoic acid and a reciprocal chromosomal
      translocation, t(15;17)(q22;q12-q21). Molecular analysis of the APL breakpoint
      has revealed the involvement of the retinoic acid receptor alpha (RARA) gene on
      chromosome 17 and the promyelocytic leukaemia (PML) gene on chromosome 15. Both
      reciprocal fusion products which arise as a result of the translocation, PML/RAR
      alpha and RAR alpha/PML, are expressed in many patients. PML/RAR alpha, is
      implicated in leukaemogenesis, and may block myeloid differentiation directly
      and/or interfere with the normal function(s) of PML and/or RAR alpha.

PMID- 8142622
TI  - Molecular basis of the t(8;21) translocation in acute myeloid leukaemia.
AB  - The t(8;21) translocation is one of the most frequent chromosomal abnormalities
      in acute myeloid leukaemia and results in gene fusion between AML1 on chromosome
      21 and MTG8 (= ETO or CDR) on chromosome 8. AML1 contains a region of sequence
      homology to the Drosophila runt gene and the mouse polyomavirus enhancer binding
      protein PEBP2 alpha gene. The rearrangement occurs within a specific intron of
      the AML1 gene and results in the formation of a chimaeric protein with the
      consistent feature that the region of sequence homology of AML1 is fused with
      almost the entire MTG8 protein. MTG8 (ETO, CDR) is predicted to be a
      transcription activation factor from its sequence with zinc-finger motifs and
      proline-rich domains. Thus the rearrangement is a fusion between two probable
      transcription activation factors.

PMID- 8142623
TI  - Rearrangements involving chromosome band 11Q23 in acute leukaemia.
AB  - Rearrangements involving chromosome band 11q23 are very common in acute
      leukaemia, both lymphoblastic and myeloid (monoblastic), and are less common in
      lymphoma. Although several different genes have been cloned from translocation
      breakpoints, the great majority of translocations involve the MLL (myeloid
      lymphoid leukaemia) gene. The MLL gene has several different names, ALL1, Htrx,
      HRX; the central part of the gene codes for multiple zinc fingers which show
      strong homology to the Drosophila trithorax gene. MLL is involved in four common
      translocations as well as in 25 uncommon or rare translocations, insertions and
      deletions. The translocation breakpoints occur within an 8.3 kb region which can
      be detected with a 0.74 kb cDNA probe. Twenty-five percent of patients have a
      deletion 3' of the breakpoint which includes the zinc finger region. Patients who
      previously received drugs that inhibit topoisomerase II often develop acute
      leukaemia with translocations involving 11q23. These translocations break MLL in
      the same 8.3 kb region. In the three breakpoints cloned to date, the
      translocation has led to a fusion gene on the derivative 11 chromosome with a
      chimaeric transcript, consisting of 5' MLL and the 3' segment of the other gene.
      Although transcripts were also cloned from the other derivative chromosome, all
      the evidence indicates that the critical fusion gene is on the derivative 11
      chromosome. The molecular dissection of these rearrangements will provide
      insights into the biology of MLL and into the interaction of MLL with
      topoisomerase II inhibitors. In addition, this research has provided DNA probes
      that will be important for diagnosis and for monitoring patients during the
      course of their disease.

PMID- 8142624
TI  - Chimaeric oncoproteins resulting from chromosomal translocations in acute
      lymphoblastic leukaemia.
AB  - A major mode of proto-oncogene activation by chromosomal translocations concerns
      the creation of fusion genes which encode chimaeric proteins. The largest class
      of oncogenes identified to date is the transcription factors, which are involved
      in control of cellular proliferation and differentiation via regulation of target
      gene transcription. Protein chimaeras that result from translocations in
      childhood ALL include two which involve the 19p13.3 gene E2A and a large
      heterogeneous group involving HRX located at chromosome band 11q23. Functional
      studies demonstrate that E2A fusion proteins function as chimaeric transcription
      factors, and structural features suggest that HRX fusion proteins may have
      analogous properties.

PMID- 8142625
TI  - The hypoxic moderation of systemic hypertension in spontaneously hypertensive
      rats.
AB  - The mechanism of hypoxic moderation of systemic systolic blood pressure was
      investigated in spontaneously hypertensive rats (SHR). Male SHR rats were divided
      into hypoxic (H, 5000 m for 15 d) and normoxic (N) groups. The systemic blood
      pressure of SHR-H (24.9 +/- 1.2 kPa) was found to be 3 kPa lower than that in SHR
      N (27.0 +/- 1.3 kPa) (P < 0.05). This protective effect may have been related to
      the adaptive changes in vascular reactivity which manifested as an increase in
      the relaxation response of the aorta to ACh (P < 0.01) and a drop in its
      contraction in response to 5-HT (P < 0.05) following hypoxic exposure. The
      hypoxic moderating effect against the development of systemic hypertension may
      have also been related to the increased plasma levels of ANP observed.

PMID- 8142626
TI  - Immunosuppression in murine brucellosis.
AB  - Brucellosis in mice results in a distinct immunosuppression which may be
      abrogated by immunomodulators, such as levamisole, bestatin, interleukin-2 (IL-2)
      and Polyporus umbellatus. The data presented here provide evidence that
      immunosuppression in addition to infection of target tissues and allergic
      reactions (including types 3 and 4) contributes to the pathogenesis of
      brucellosis. The present study also provides some basic data regarding the value
      of this animal model, and criteria for observing the effect of therapy on chronic
      brucellosis.

PMID- 8142627
TI  - Detection of the HPV16 E6 transforming gene by PCR in tissue samples from normal
      cervix and from cervix with precancerous lesions and carcinomas.
AB  - A study of 130 biopsies from cases of histologically confirmed normal cervix
      (30), cervicitis (28), cervical intraepithelial neoplasia (CINI-CIN III, 29), and
      cervical cancer (43) was performed to determine the presence of human
      papillomavirus (HPV) type 16 DNA sequences. The polymerase chain reaction
      technique was adopted using two oligonucleotides as primer pairs in the HPV16
      early 6 (E6) gene open reading frame (ORF). The rates of HPV16 infection in
      normal tissues, cervicitis, CINI-CIN III and cervical cancer were found to be
      16.67% (5/30), 25.00% (7/28), 41.38% (12/29) and 69.77% (30/43), respectively.
      Statistical analysis showed that the relative risk (RR) of association between
      HPV16 infection and the development of cervicitis, CINs and cervical carcinomas
      was increased with the severity of cervical lesions, from 1.0 (normal) to 1.67,
      4.62 (P < 0.05; 95% CI 0.28-8.95) and 11.54 (P < 0.001; 95% CI 3.94-33.81),
      respectively. Our results strongly support the idea that the development of
      cervical precancerous lesions and cervical carcinomas is closely associated with
      HPV16 infection.

PMID- 8142628
TI  - Clinical significance of cellular DNA ploidy in rectal cancer less than 3 cm in
      diameter.
AB  - Cellular DNA ploidy of paraffin-embedded tumor tissues from 51 patients with
      rectal cancer less than 3 cm in diameter was determined by flow cytometry. The
      relationship of DNA ploidy to Dukes stage, histological grade, lymph node
      metastasis and to the survival rate of postoperative patients was analyzed. The
      incidences of diploid tumors in patients with Dukes stage A, B and C tumors were
      83%, 52% and 21%, respectively. There were significantly more patients with lymph
      node metastasis in the nondiploid cancer group than in the diploid cancer group.
      Patients with diploid cancer had significantly better 5-year and cumulative
      survival rates than did patients with nondiploid cancer. The results suggest that
      analysis of cellular DNA ploidy can provide a new prognostic parameter for rectal
      cancer less than 3 cm in diameter.

PMID- 8142629
TI  - Vasoactive intestinal peptide stimulates the growth of rat hepatoma cells in
      vitro.
AB  - Using tetrazolium colorimetric assay (MTT assay) and cell counting methods, the
      effect of vasoactive intestinal peptide (VIP) on the growth of cultured rat
      hepatoma FSK-7902 cells was investigated. The results showed that VIP obviously
      stimulated the proliferation of the rat hepatoma cells. The growth promoting
      effect increased with VIP concentration. Exposure to VIP for 12 h followed by
      removal of the peptide resulted in sustained growth promotion for several days.

PMID- 8142630
TI  - Protective effect of Salmonella typhimurium Re-LPS antiserum.
AB  - There is increasing evidence that antiserum to LPS can reduce the morbidity and
      mortality of Gram-negative bacterial infections. We report that antiserum to S.
      typhimurium SL 1102 (Re mutant strain) has excellent cross-protective activity.
      Antisera to these bacteria and to their Re-LPS were prepared in rabbits immunized
      with heat-killed bacterial cells and with Re-LPS preparations. Re-LPS antibody
      titers were tested by immune hemagglutination (IHA) and by ELISA. These antisera
      were found to be capable of protecting ICR mice against lethal challenge with S
      type S. typhimurium 50014 (100 LD50), E. coli 0111:B4 (32 LD50), Pseudomonas
      aeruginosa (8 LD50) and Klebsiella pneumonia (16 LD50). We used gastric mucin
      (5%) as a virulence enhancing agent for the bacterial challenges. The IHA titer
      of antibody to the homologous strain proved to be much higher than that of other
      strains. Protection by the sera was 75-100%, 25% and 0% when injected 24, 48 or
      72 h before the challenge, respectively. The survival rate was more than 50% when
      the antiserum was injected 5-7 h after challenge with a ten-fold or higher lethal
      dose. No protection was observed against such high challenge when the serum was
      injected later. According to these results, Re-LPS antiserum provides better
      protection than S-type specific antisera.

PMID- 8142631
TI  - Plasmid analysis and phage typing in the study of staphylococcal colonization and
      disease in newborn infants.
AB  - Plasmid analysis, bacteriophage typing and antibiograms were used to detect the
      source and rate of Staphylococcus aureus colonization and disease in newborn
      infants in a nursery. Staphylococcal colonization on the nasal mucosa and
      umbilicus of 140 neonates took place within 12 hours after birth. The
      colonization rates reached 100% from the fourth day onward and fell to 66.7%,
      25.5% and 17.5% by the age of 1 month, 6 months and 1 year, respectively. The
      incidence of nursery-acquired infection caused by S. aureus was at least 16.4%.
      All infections were confined to the skin or mucosa and were not serious. It is
      believed that the S. aureus which colonized and infected the newborn infants
      mainly originated from the nares and the hands of nurses, because only S. aureus
      strains from nurses and infected infants had the same phage patterns
      (52/52A/47/53/75/77/81) and carried 2 plasmids of the same size (1.4 and 1.7 Md),
      whereas S. aureus isolated from other sources did not have the same phage
      patterns or plasmid profiles. In view of the results of this study, it is
      considered that the importance of careful washing of the hands of personnel
      before and after handling infants should be emphasized.

PMID- 8142632
TI  - Fukuyama type congenital muscular dystrophy with central-temporal EEG foci
      (rolandic spikes).
AB  - Central-temporal EEG foci (rolandic spikes) in three patients who satisfied all
      the diagnostic criteria for Fukuyama type congenital muscular dystrophy (FCMD)
      are reported. Clinically one case remained silent and two cases were accompanied
      by epileptic seizures, characterized as follows: 1) partial seizures with
      elementary motor symptomatology; 2) brief and rare seizures, but occasionally
      with frequent or prolonged convulsions; 3) seizures were easily induced by
      defined precipitating factors such as fever; 4) seizures could be quickly
      controlled by routine antiepileptic treatment. Electroencephalographically, the
      appearance of repetitive stereotyped diphasic spikes over central and mid
      temporal areas were quite similar to those described in rolandic epilepsy. We
      believe that the EEG findings in our cases corroborate the postulation that the
      prognosis is as good in these severely brain-damaged children as in normal
      children in terms of recovery from the epilepsy.

PMID- 8142633
TI  - Application of Steffee operation in spinal surgery.
AB  - Steffee operation is a surgical method of internal fixation for unstable
      conditions of the spine. Up to March 1991, 32 cases of various spine disorders
      were treated with the Steffee system in our hospital. These operations brought
      good results, as 83.4% of the cases received either good or excellent functional
      and clinical ratings postoperatively. Among patients with spondylolisthesis, the
      degree of slip correction averaged 58.5% postoperatively. Neurological
      complications are avoided by accurate localization of the screws.

PMID- 8142634
TI  - Growth factor gene expression in bronchoalveolar lavage cells from patients with
      lung fibrosis.
AB  - We have studied the gene expression of ten growth factors in bronchoalveolar
      lavage (BAL) cells from patients with lung fibrosis by using a reverse
      transcription-DNA polymerase chain reaction (RT-PCR) technique. IL-1 beta mRNA
      was detected in almost all of the samples, and TGF beta and IGF-I mRNA were
      detected in some. The BAL supernatant from the patients was found to have
      mitogenic activity for lung fibroblasts. Moreover, human recombinant IL-1 beta,
      TGF beta and IGF-I were found to promote the proliferation of lung fibroblasts.
      These data suggest that IL-1 beta, TGF beta and IGF-I gene expression in BAL
      cells might be involved in the development of lung fibrosis.

PMID- 8142635
TI  - Atrial fibrillation and coronary artery disease.
AB  - A retrospective study of the incidence of atrial fibrillation in 703 consecutive
      patients who had undergone selective coronary arteriography and left ventricular
      catheterization between November 1986 and May 1992 was undertaken. The study
      group included 136 patients with significant coronary stenosis (> 50% diameter
      reduction) without previous myocardial infarction (group I), 157 with a history
      of myocardial infarction (group II), 326 with chest pain and normal coronary
      angiography (group III), 72 with valvular disease (group IV), and 12 with
      cardiomyopathy (group V). Clinical and electrocardiographic evidence of atrial
      fibrillation was documented in 75 patients (10.7%), including 2 (1.5%) in group
      I, 6 (3.8%) in group II, 36 (11%) in group III, 27 (37.5%) in group IV, and 4
      (33.3%) in group V. The rate of occurrence of atrial fibrillation was lower in
      groups I and II than in groups III, IV and V. Atrial fibrillation was rarely
      found in coronary artery disease.

PMID- 8142636
TI  - Molecular basis of PKU in China.

PMID- 8142637
TI  - Treatment of 121 patients with malignant effusion due to advanced lung cancer by
      intrapleural transfer of autologous or allogeneic LAK cells combined with rIL-2.
AB  - Lymphocytes isolated from malignant pleural effusion in patients with advanced
      lung cancer or from allogeneic peripheral blood of healthy donors were induced to
      become LAK cells after in vitro culture with rIL-2. One hundred and twenty-one
      patients with malignant effusions were treated by intrapleural transfer of
      autologous or allogeneic LAK cells combined with rIL-2. The effusion disappeared
      in 71 patients (58.6%) and was significantly decreased in 45 patients (36.2%).
      Five patients did not respond to treatment. Tumor cells in pleural effusions
      disappeared or were significantly decreased in number, whereas the lymphocytes
      were significantly increased in number in all responders. Except for transient
      fever in 10 patients, no serious side effect was observed.

PMID- 8142638
TI  - Why better prognostic factors for multiple myeloma are needed.

PMID- 8142639
TI  - Immunoglobulin V regions and the B cell.
AB  - There is now substantial evidence that a small group of V genes predominates in
      the Ig repertoire of preimmune B cells. This phenomenon of V gene restriction may
      reflect preferential accessibility of these genes to recombinase, homology
      directed V gene rearrangement, promoters and enhances of V gene transcription, or
      positive and negative selection mediated by the anti-self binding properties of
      the B cells surface Ig. These mechanisms may operate alone or in combination to
      influence V gene rearrangement and populations of immature B cells. Although
      constraints on the pool of rearranged V genes may seem disadvantageous to the
      immune system, the mechanisms that generate the CDR3s of heavy and light chains
      ensure extensive diversity in the pre-B-cell population. In mature B cells,
      somatic mutation of V genes adds further diversity. CDR3 sequences and somatic
      mutations not only provide potentially useful clonal markers but also help to
      identify the normal counterparts of malignant B cells.

PMID- 8142640
TI  - Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk
      acute lymphoblastic leukemia.
AB  - We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic
      and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL)
      was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia,
      causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99%
      (median 83.5%) of those in parallel cultures not exposed to the cytokine. All
      nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal
      features that are often associated with multidrug resistance and a fatal outcome,
      were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of
      programmed cell death (apoptosis); there was no evidence of cell killing mediated
      by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a
      proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100
      U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived:
      in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL
      4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated
      bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001
      by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell
      precursors and support clinical testing of IL-4 in cases of high-risk
      lymphoblastic leukemia resistant to conventional therapy.

PMID- 8142641
TI  - Variable transcription of BCR-ABL by Ph+ cells arising from hematopoietic
      progenitors in chronic myeloid leukemia.
AB  - Recent studies suggest that the BCR-ABL gene plays a critical role in the
      pathogenesis of Ph+ chronic myeloid leukemia (CML). We investigated the
      hematopoietic colonies derived from the marrows of 12 patients with Ph+ CML in
      chronic phase by reverse transcriptase-polymerase chain reaction (RT-PCR)
      amplification of BCR-ABL mRNA and by cytogenetics. Colonies were individually
      harvested and each colony divided into two portions, one for cytogenetics and the
      other for isolation of total RNA for PCR of BCR-ABL transcripts and for an RNA
      internal control. We found that 23% +/- 18% (mean +/- SD, range 0% to 60%) of Ph+
      colonies did not transcribe the aberrant gene. In each case when BCR-ABL
      transcription was not detected, normal ABL mRNA was present. The data suggest
      that hitherto unknown mechanisms may regulate BCR-ABL expression in some Ph+
      cells and indicate that caution should be exercised in the interpretation of
      results using RT-PCR analysis of hematopoietic colonies from clinical specimens
      and from experiments with antisense oligonucleotides directed at the BCR-ABL
      gene. These data also raise the notion of a transitional Ph+ precursor cell in
      which BCR-ABL may become upregulated and lead to a fully expressed phenotype. We
      conclude that further studies correlating the frequency of Ph+ PCR- progenitors
      with prognostic clinical variables are warranted.

PMID- 8142642
TI  - Detection of fusion transcripts generated by the inversion 16 chromosome in acute
      myelogenous leukemia.
AB  - Pericentric inversion of chromosome 16 [inv(16)(p13q22)] and the related
      t(16;16)(p13;q22) are seen in a subset of acute myelogenous leukemia (AML)
      phenotypically and prognostically differing from other cases. We have recently
      shown that inv(16) results in fusion of CBFB/PEBP2B, a gene encoded at 16q22 to
      MYH11, a smooth muscle myosin heavy chain gene encoded at 16p13. Chimeric
      transcripts consisting of upstream CBFB fused to downstream MYH11 coding
      sequences result from this fusion. In this study we have examined a series of 37
      of these cases using reverse transcriptase-polymerase chain reaction (RT-PCR) to
      detect expression of a hybrid CBFB/MYH11 transcript. Chimeric cDNAs were detected
      in all but 1 of 37 leukemias with typical inv(16) or t(16;16). Such chimeric
      products were not seen in a case with inv(16)(p13q24) (ie, a variant q arm
      breakpoint) or any of 10 cases of AML without these chromosomal changes. Four
      different chimeric transcripts were found, representing differing fusion points
      within MYH11 spliced to position 495 of CBFB. Primer sets are described for
      efficient amplification of these different cDNA forms. Amplification of cDNA
      showed that all but 17 codons of the CBFB coding sequence are included in the
      abnormal transcripts. RT-PCR was shown to be highly sensitive and potentially
      useful for detection of leukemic cells during morphologic remission.

PMID- 8142643
TI  - Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin's lymphoma.
AB  - The pathogenesis of non-Hodgkin's lymphoma (NHL) with a large cell component
      (DLLC, including diffuse large cell, DLCL; diffuse mixed cell, MX-D; and
      immunoblastic, IMB) is unknown. A novel candidate proto-oncogene, BCL6, that is
      involved in chromosome band 3q27 aberrations in NHL has been recently identified.
      We have investigated the incidence and disease-specificity of BCL6 rearrangements
      in a large panel of lymphoid tumors, including acute and chronic lymphoid
      leukemias (96 cases), various NHL types (125 cases), and multiple myelomas (23
      cases). BCL6 rearrangements were found in 16/45 (35.5%) DLLC, more frequently in
      DLCL (15/33, 45%) than in MX-D (1/10, 10%), in 2/31 (6.4%) follicular NHL, and in
      no other tumor types. BCL6 rearrangements represent the first genetic lesion
      specifically and recurrently associated with DLLC and should prove useful for
      understanding the pathogenesis as well as for the clinical monitoring of these
      tumors.

PMID- 8142645
TI  - Stable multilineage hematopoietic chimerism in alpha-thalassemic mice induced by
      a bone marrow subpopulation that excludes the majority of day-12 spleen colony
      forming units.
AB  - We have investigated the contribution of highly purified day-12 spleen colony
      forming units (CFU-S-12) as well as more primitive cells to sustained blood cell
      production using in vivo and in vitro assays that allow frequency analysis.
      Normal or day-6 post-5-fluorouracil light-density bone marrow (BM) was sorted on
      the basis of differences in rhodamine-123 (Rh123) retention or wheat germ
      agglutinin (WGA) affinity and tested in vivo using a recently developed alpha
      thalassemic chimeric mouse model. In addition, short-term and long-term clonal
      activity was assessed in vitro using a limiting dilution-type long-term BM
      culture, the cobblestone area forming cell assay. When sublethally irradiated
      alpha-thalassemic mice were transplanted with as many as 281 purified WGAbright
      CFU-S-12, derived from a fraction containing 95% of all CFU-S-12 from day-6 post
      5-fluorouracil light-density BM of wild-type mice, detectable chimerism was not
      observed at 6 months posttransplantation. In contrast, only three CFU-S-12 were
      included in the Rh123dull and WGAdim subpopulations that induced 29% to 58% and
      21% to 31% stable multilineage donor-type chimerism of erythrocytes and
      leukocytes, respectively. The Rh123dull and WGAdim cells were up to 240-fold
      enriched for long-term repopulating ability (LTRA) as compared with unseparated
      BM. A comparable level of chimerism was found in the different hematopoietic
      organs and at the level of BM CFU-S-12. The frequency of the LTRA unit capable of
      inducing a 10% sustained level of donor-type erythrocytes was calculated to be 1
      to 2 per 10(5) BM cells. Several reports have suggested that LTRA and spleen
      colony formation could be capacities of the same stem cell subset. However, the
      present results show that the majority of CFU-S-12 have only short-term
      repopulating ability and are physically separable from more primitive stem cells
      with long-term multilineage reconstituting capacities.

PMID- 8142644
TI  - A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid
      leukemia: specific targeting without immunogenicity.
AB  - This trial studied the biodistribution, pharmacology, toxicity, immunogenicity,
      and biologic characteristics of a trace-labeled, anti-CD33, humanized monoclonal
      antibody M195 (Hu-M195) in patients with relapsed and refractory myeloid
      leukemia. Hu-M195 is a computer-modeled, "complementarity-determining region
      grafted," IgG1, humanized version of M195. M195 is a murine monoclonal antibody
      that reacts with CD33, a 67-kD glycoprotein expressed on early myeloid progenitor
      cells and myeloid leukemia (acute myelogenous leukemia and chronic myelogenous
      leukemia) cells, but not normal stem cells. 131I-murine-M195 has already shown
      significant ability to cytoreduce patients with relapsed or refractory myeloid
      leukemias. Hu-M195 has higher avidity than the original mouse monoclonal antibody
      and, unlike murine M195, has the capability to mediate antibody-dependent
      cellular cytotoxicity against leukemia targets. Thirteen patients with relapsed
      or refractory myelogenous leukemia were treated with Hu-M195 at 4 levels of 0.5,
      1.0, 3.0, and 10.0 mg/m2 in a phase I trial. Patients received a total of 6 doses
      per patient over 18 days. Two patients were retreated for a total of 12 doses.
      The first dose of Hu-M195 was trace-labeled with 131I to allow detailed
      pharmacokinetic and biodistribution studies by serial sampling of blood,
      radioimmunoassays of cells, and whole-body gamma-camera imaging. Cumulative total
      doses of up to 216 mg of Hu-M195 were administered safely. Reversible fever and
      rigors were observed after infusion at the highest dose levels. The entire bone
      marrow was specifically and clearly imaged within hours after infusion, with
      optimal biodistribution occurring at the 3 mg/m2 level. Adsorption of Hu-M195
      onto targets in vivo was demonstrated by flow cytometry; near saturation of
      available sites occurred at the 3 mg/m2 dose level. Plasma and whole body half
      lives were 38 and 51 hours, respectively, which may reflect continual
      replenishment of target sites on new leukemia cells. 131I-Hu-M195 was rapidly
      internalized into the target cells in vivo within 1 hour. Human antihuman
      antibody responses were not observed. In conclusion, Hu-M195 can be administered
      safely in multiple doses, without significant toxicity or any evidence of
      immunogenicity, and can localize rapidly and efficiently to the bone marrow in
      patients with myeloid leukemias. Additional phase II trials with this agent alone
      or in combination with cytokines or isotopes are warranted at the optimal
      biologic dose.

PMID- 8142646
TI  - Dissociation between p93B-myb and p75c-myb expression during the proliferation
      and differentiation of human myeloid cell lines.
AB  - Direct and indirect evidence strongly indicates that the proto-oncogene c-myb
      plays an important role in the regulation of both the proliferation and
      differentiation of hematopoietic cells. In addition, recent data suggest that the
      structurally related B-myb gene is also necessary for the proliferation of these
      cells. To help understand the relationship between these two related gene
      products during proliferation and differentiation of myeloid cells, we have
      studied in parallel the regulated expression of c-myb and B-myb RNAs and proteins
      in human myeloid cells that were either growth-arrested or induced to
      differentiate along different pathways. For this purpose, we have produced a
      polyclonal antibody directed against a fragment of the recombinant B-myb protein.
      We have thus been able to detect the B-myb protein in human cell lines and have
      found it to be a 93-kD protein localized in the nucleus. We have chosen two
      models to study the expression of both c-myb and B-myb mRNAs and proteins during
      myeloid proliferation and differentiation. One of the models was the HL-60 cell
      line, which can be induced to differentiate towards the monocytic pathway with
      either phorbol ester (phorbol myristate acetate) or vitamin D3 and towards the
      granulocytic pathway with either dimethyl sulfoxide or retinoic acid. In
      addition, we have studied another recently established human leukemic cell line,
      called GF-D8, which is strictly dependent on granulocyte-macrophage colony
      stimulating factor (GM-CSF) for proliferation. The results show that the
      expression of B-myb RNA and protein closely correlates with proliferation in all
      experimental setups studied, whereas the c-myb protein levels do not always do
      so. We observed that the c-myb protein levels decreased well before the decrease
      of B-myb protein and of proliferation itself during differentiation toward
      monocytes. Such a difference was not present during granulocytic differentiation,
      in which c-myb levels decreased, if anything, later than those of B-myb and
      proliferation. Most striking was the finding that high levels of c-myb RNA and
      protein, but not of B-myb, were present in the GF-D8 cell line, even after growth
      arrest by GM-CSF deprivation. These data suggest that B-myb may function solely
      in the regulation of cellular proliferation, whereas c-myb has additional
      functions, for example, in the maintenance of an undifferentiated state.

PMID- 8142647
TI  - Interleukin-3 and granulocyte-macrophage colony-stimulating factor induce
      activation of the MAPKAP kinase 2 resulting in in vitro serine phosphorylation of
      the small heat shock protein (Hsp 27).
AB  - Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) have previously been reported to induce rapid phosphorylation of the mitogen
      activated protein (MAP) kinase. However, little is known about signaling events
      initiated by both hematopoietins that occur downstream of the MAP kinase. MAP
      kinase has been shown to phosphorylate the AP-1 transcription factor and also to
      activate two kinases designated insulin-stimulated protein kinase-1 and MAP
      kinase-activated protein (MAP-KAP) kinase 2. We show here that IL-3 and GM-CSF
      induce MAPKAP kinase 2 activity in the human megakaryoblastic leukemia cell line
      MO7 and phosphorylate the human small heat shock protein Hsp 27 on serine
      residues in vitro. GM-CSF also induced Hsp 27 phosphorylation in neutrophils in a
      range similar to that observed in MO7 cells, suggesting that MAPKAP kinase 2
      mediated Hsp 27 activation occurs independently of proliferation. Hsp 27
      phosphorylation was dose-dependent, occurred as early as 5 minutes after factor
      exposure, and was inhibited by the tyrosine kinase inhibitors genistein and
      herbimycin A. Furthermore, the protein phosphatase A2 abolished IL-3- and GM-CSF
      induced serine phosphorylation of Hsp 27. Taken together, our findings indicate
      that tyrosine phosphorylation of MAP kinase is a prerequisite for serine
      phosphorylation of Hsp 27, which is mediated by MAPKAP kinase 2. Hsp 27 has shown
      activation-dependent translocation from the cytosolic to the nuclear region and
      has been linked to the cellular stress response. However, its precise function is
      largely unknown. Our data identify Hsp 27 as a target of the IL-3/GM-CSF
      stimulation pathway that involves MAP kinase and MAPKAP kinase 2. In addition,
      our results indicate that Hsp 27 may be target of phosphorylation events not only
      in the stress response but also in unstressed cells responding to cytokine
      stimulation.

PMID- 8142648
TI  - Establishment of two permanent human bone marrow stromal cell lines with long
      term post irradiation feeder capacity.
AB  - We describe the establishment of two permanent Simian virus 40-transformed human
      stromal cell lines, designated L87/4 and L88/5, derived from the bone marrow of a
      hematologically normal male patient. Both cell lines show a fibroblastoid
      morphology and do not express hematopoietic cell markers. L87/4 but not L88/5
      expresses the macrophage marker CD68. The most remarkable feature of these new
      stromal cell lines is their ability to persist as growth-arrested adherent feeder
      cells after ionizing-irradiation at doses up to, and exceeding 20 Gy (L87/4).
      This renders them particularly useful for studying aspects of feeder dependence
      of hematopoietic cell development in long-term culture. Both cell lines are able
      to function as feeder cells, supporting the long-term proliferation of CD34+
      human cord blood cells as well as the clonogenic growth of the human Burkitt
      lymphoma B-cell line BL70.

PMID- 8142649
TI  - Basic fibroblast growth factor antagonizes transforming growth factor beta
      mediated erythroid differentiation in K562 cells.
AB  - Basic fibroblast growth factor (bFGF) and transforming growth factor-beta 1 (TGF
      beta) have both been shown to act on hematopoietic progenitor cells. bFGF is a
      hematopoietic cytokine that acts on progenitor cells in concert with other
      cytokines to promote their proliferation. TGF-beta induces erythroid
      differentiation in K562 cells. To determine whether bFGF might act on progenitor
      cells by antagonizing the effects of cytokines that induce differentiation, we
      determined the effects of bFGF on the TGF-beta-mediated induction of hemoglobin
      synthesis in K562 cells. bFGF antagonized the TGF-beta-mediated induction of
      hemoglobin in a dose-dependent manner, with 0.1 ng/mL bFGF inhibiting hemoglobin
      induction by 40% and 10 ng/mL bFGF completely abrogating hemoglobin production.
      bFGF was most effective at antagonizing the TGF-beta-mediated induction of
      hemoglobin if it and TGF-beta were added simultaneously to K562 cells, but
      delayed addition of bFGF to TGF-beta-treated cultures still resulted in
      significant inhibition of hemoglobin synthesis. The inhibitory effects of bFGF on
      hemoglobin production were fully reversible, showing that bFGF did not
      permanently alter the phenotype of K562 cells. The hemin-mediated induction of
      hemoglobin synthesis in K562 cells was only partially negated by bFGF. bFGF also
      diminished the expression of glycophorin A on the surface of K562 cells. These
      results indicate that bFGF might increase progenitor/stem cell numbers by
      antagonizing the effects of cytokines that induce differentiation, thereby
      increasing the pool of proliferating progenitor/stem cells.

PMID- 8142650
TI  - Putative oncogenic role of the erythropoietin receptor in murine and human
      erythroleukemia cells.
AB  - To determine whether the erythropoietin receptor (Epo-R) plays a role in the
      course of malignant erythropoietic disorders, this gene was studied in murine and
      human erythroleukemia cells. An altered Epo-R gene was found in a murine Friend
      erythroleukemia cell line, FCL1, due to a spleen focus-forming virus (SFFV) long
      terminal repeat insertion within the noncoding region of the first exon, leading
      to Epo-R mRNA overexpression. A similar mechanism of Epo-R activation has
      previously been described in the T3CL-2 Friend erythroleukemia cell line. An
      elevated number of Epo-binding sites has been observed in two human
      erythroleukemia cell lines, TF-1 and UT7. In UT7 cells, homogeneously staining
      region of the short arm of chromosome 19 [hsr (19)] was evidenced, which
      contained an amplification of the Epo-R gene. This Epo-R gene amplification was
      confirmed by the quantification of Southern blots in which the intensity of the
      Epo-R signal was compared in UT7 DNA and in DNA from normal cells. The Epo-R gene
      was present in UT7 at a mean number of seven to eight copies per cell.
      Interestingly, the Epo-R gene was rearranged; the breakpoint region was located
      near the 3' end of the gene, 3 kb downstream from the end of the last exon. Taken
      together, these results suggest that, in both murine and human systems, genetic
      alterations of the Epo-R gene are not rare events and could be involved in the
      occurrence of the erythroleukemic process.

PMID- 8142651
TI  - Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta
      in vascular smooth muscle cells.
AB  - We have investigated the role of platelets in regulating the hemostatic and
      vasomotor properties of vascular smooth muscle. Experiments were performed to
      examine the effect of the releasate from activated platelets on the production of
      nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured rat aortic
      smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta
      resulted in significant accumulation of nitrite in the culture media and in
      marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels.
      The releasate from collagen-aggregated platelets blocked the IL-1 beta-mediated
      production of nitrite and the accumulation of cyclic GMP in smooth muscle cells
      in a platelet number-dependent manner. In functional assays, the perfusates from
      columns containing IL-1 beta-treated smooth muscle cells relaxed detector blood
      vessels without endothelium and the addition of IL-1 beta-treated smooth muscle
      cells to suspensions of platelets inhibited their thrombin-induced aggregation.
      The simultaneous treatment of smooth muscle cells with IL-1 beta and the platelet
      releasate abolished both the vasorelaxing activities of the perfusates and the
      inhibition of platelet aggregation. Platelet releasates treated with a
      neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL
      1 beta-induced nitric oxide production by the smooth muscle cells, as measured by
      both biochemical and functional assays. The platelet releasate from a patient
      with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite
      release by smooth muscle cells. These results demonstrate that platelets
      downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth
      muscle cells through the release of PDGF. This effect may represent a novel
      mechanism by which platelets regulate vasomotor tone and thrombus formation at
      sites of vascular injury.

PMID- 8142652
TI  - Multiple cis-acting elements in the human immunodeficiency virus type 2 enhancer
      mediate the response to T-cell receptor stimulation by antigen in a T-cell
      hybridoma line.
AB  - Transcription directed by the human immunodeficiency virus type 2 long terminal
      repeat (HIV-2 LTR) responds to T-cell antigen receptor signaling. Agents that
      stimulate T-cell signaling pathways activated by the antigen receptor, such as
      phorbol ester, plant lectin, or anti-CD3 antibody treatment, have been shown to
      increase transcription directed by the HIV-2 LTR. In this study, we examine the
      activation of the HIV-2 LTR in T cells stimulated with the physiologic ligand of
      the T-cell receptor, antigenic peptide presented by a major histocompatibility
      molecule. HIV-2 reporter plasmids were transfected into the antigen-specific T
      cell hybridoma, 2B4.11, where they responded to antigen-dependent activation.
      This antigen-mediated transcriptional activation of the HIV-2 enhancer required
      the presence of at least four regulatory elements in the HIV-2 enhancer,
      including two purine boxes, PuB1 and PuB2, an AP-1/CREB-like element (pets), and
      kappa B. This finding suggests that signals emanating from the antigen receptor
      act coordinately on a set of transcription factors that bind to conserved HIV-2
      regulatory elements. Despite differences in the organization of potentially
      related enhancer elements in HIV-2 and IL-2, these enhancers exploit a similar
      signal transduction pathway to induce gene expression in antigen-activated T
      cells.

PMID- 8142653
TI  - Detection of the chromosomal translocation t(11;14) by polymerase chain reaction
      in mantle cell lymphomas.
AB  - The t(11;14)(q13;q32) and its molecular counterpart, BCL1 rearrangement, are
      consistent features of mantle cell lymphoma (MCL). Rearrangement is thought to
      deregulate the nearby CCND1 (BCL1/PRAD1) proto-oncogene, a member of the cyclin
      G1 gene family, and thereby to contribute to tumorigenesis. We and others have
      previously shown that the BCL1 locus is rearranged in 55% to 60% of MCL patients
      and that, on chromosome 11, more than 80% of the breakpoints are localized within
      a 1-kbp DNA segment known as the major translocation cluster (MTC). We have
      determined the nucleotide sequence for a portion of the MTC region, and
      constructed chromosome 11-specific oligonucleotides that were in conjunction with
      a consensus immunoglobulin (Ig) heavy chain joining region (JH) primer used to
      perform the polymerase chain reaction (PCR) to amplify t(11;14) chromosomal
      junctional sequences in DNA from 16 MCL patients with breakpoints in the MTC
      region. 15 of the 16 breakpoints that occurred at the MTC region were amenable to
      PCR detection. The sizes of the amplified bands, the existence or not of a Sac I
      site in the PCR products, and nucleotide sequencing of the amplified DNA from
      four patients showed that the breakpoints share a remarkable tendency to tightly
      cluster within 300 bp on chromosome 11, some of them occurring at the same
      nucleotide. On chromosome 14, the breakpoints were localized within the Ig JH.
      Our findings indicate that a BCL1 rearrangement can be detected using this
      approach in roughly one half of the MCL patients. This has implications for both
      the diagnosis and the clinical management of MCL.

PMID- 8142654
TI  - Downregulation of Wilms' tumor gene (wt1) during myelomonocytic differentiation
      in HL60 cells.
AB  - The putative Wilms' tumor-suppressor gene (wt1) encodes a zinc finger DNA binding
      protein that functions as a transcription repressor. The wt1 gene expression
      corresponds to kidney development, suggesting a role for this gene in nephroblast
      differentiation. Here we show that wt1 mRNA expression was downregulated during
      terminal differentiation of promyelocytic HL60 cells. When HL60 cells were
      induced to differentiate to granulocytes by dimethyl sulfoxide (DMSO) or retinoic
      acid (RA), a marked downregulation in the levels of wt1 transcripts was found.
      The wt1 transcripts were also downregulated in HL60 cells during differentiation
      to monocytes by vitamin D3 or 12-o-tetradecanoyl-phorbol-13-acetate. Nuclear run
      on transcription studies showed the transcriptional rate of wt1 gene was not
      significantly altered during DMSO-induced granulocytic differentiation,
      suggesting the downregulation was mostly caused by posttranscriptional
      modification. Importantly, wt1 transcripts were not significantly altered in K562
      cells by treatments with DMSO or RA, which do not induce differentiation of K562
      cells. These findings suggest that wt1 gene expression may be downregulated as a
      differentiation-linked event in HL60 cells.

PMID- 8142655
TI  - Induction of differentiation of promyelocytic NB4 cells by retinoic acid is
      associated with rapid increase in urokinase activity subsequently downregulated
      by production of inhibitors.
AB  - 13-trans retinoic acid (13-trans RA) is an effective inducer of differentiation
      of acute promyelocytic (APL) cells both in vivo and in vitro. It is used in the
      induction of remission of patients with APL. We found, by using the promyelocytic
      NB4 cell line established from a patient with APL, that the induction of
      differentiation with RA was accompanied by modulation of the plasminogen
      activation system. The expression of urokinase (uPA) activity was rapidly
      increased in the growth medium and at the surface of cells treated with RA. The
      high uPA activity was counteracted both in the growth medium and at the cell
      surface by an increased plasminogen activator inhibitor (PAI) production and
      reduction of uPA synthesis. The expression of uPA receptor and PAI-2 were
      stimulated and persisted at 48 hours from RA addition. The simultaneous induction
      of CD11b suggests that differentiation results in increased production of both.
      APL patients often encounter episodes of disseminated intravascular coagulation
      that are associated with secondary fibrinolytic events. Our results suggest that
      downregulation of uPA activity results in the decrease of plasmin on the surface
      of the differentiated cells, which may reduce the occurrence of fibrinolytic
      episodes of patients with APL.

PMID- 8142656
TI  - Prospective monitoring and quantitation of residual blasts in childhood acute
      lymphoblastic leukemia by polymerase chain reaction study of delta and gamma T
      cell receptor genes.
AB  - We have developed a strategy based on polymerase chain reaction (PCR) for
      detecting all possible gamma T-cell receptor (gamma TCR) rearrangements and the
      most common delta TCR rearrangements found in B-lineage and T-acute lymphoblastic
      leukemia (T-ALL). The segments amplified from blasts are then directly sequenced
      to derive clonospecific probes. From a series of 45 patients aged 1 to 15 years
      (42 B-lineage ALL, 3 T-ALL), 35 (83%) could be followed for minimal residual
      disease with at least one clonospecific probe. Detection of clonal markers using
      clonospecific probes routinely allowed the detection of 1 to 10 blasts out of
      10(5) cells as determined by serial dilutions of the initial samples. Residual
      disease was quantitated by a competitive PCR assay based on the coamplification
      of an internal standard. Twenty children were prospectively followed for periods
      varying from 7 to 30 months. In most children, a progressive decrease of the
      tumor load was observed, and blasts became undetectable within 6 months after the
      initiation of treatment. A slower kinetics of decrease in tumor cells was found
      in three children. These three patients relapsed with blasts that continued to
      display the initial clonospecific markers. Three other children had a central
      nervous system relapse despite the absence of detectable medullary residual
      disease. The use of both delta and gamma TCR genes as clonal markers, as well as
      simplification in the methods to detect and quantify residual blasts reported
      here, will allow the study of the large number of patients required to determine
      the role of the detection of minimal residual disease by PCR in the follow-up of
      childhood ALL.

PMID- 8142657
TI  - High levels of interleukin-6 are associated with low tumor burden and low growth
      fraction in multiple myeloma.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine postulated to play a central
      role as a growth factor for multiple myeloma (MM). We evaluated the spontaneous
      secretion of IL-6 in supernatants of Ficoll-Hypaque--enriched bone marrow (BM)
      cultures from 35 patients with MM. The levels of IL-6 were correlated with
      biological and clinical characteristics of the disease. High levels of IL-6
      production defined a subgroup of patients with low tumor burden as determined by
      lower serum beta 2-microglobulin (B2M) (P = .02) and lower percentage of myeloma
      cells infiltrating the bone marrow (P = .003), higher synthetic rates of
      monoclonal protein (P = .006), and low proliferative compartments as measured by
      the percentage of Ki-67--positive myeloma cells. Patients with high proliferative
      fractions (Ki-67--positive myeloma cells > 20%) had significantly lower levels of
      IL-6 when compared with patients with low proliferative fractions (P = .005). Our
      findings do not support IL-6 as a major growth factor for MM, but demonstrate an
      association of high levels of IL-6 secretion with low tumor cell burden and low
      proliferative fraction.

PMID- 8142658
TI  - Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in
      chronic myeloid and acute lymphoblastic leukemia by in situ hybridization.
AB  - The presence of BCR-ABL fusion genes has important diagnostic and prognostic
      implications in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia
      (ALL). The CML-specific chimeric BCR-ABL gene with a break involving the major
      breakpoint cluster region (M-bcr) of the BCR-gene has been detected by means of
      fluorescence in situ hybridization (FISH). In this study, we present a FISH
      protocol that allows the detection of breaks in both the major and the minor
      breakpoint cluster region (m-bcr). Three hybridization signals of D107F9, a yeast
      artificial chromosome (YAC)-derived probe spanning the breakpoint regions of the
      BCR gene, were indicative of the translocation events. To increase the
      specificity further, this probe was combined with cos-abl 8, a cosmid probe
      flanking the breakpoint within the ABL gene for dual-color hybridization. Samples
      of 21 patients with CML, the ALL-derived cell line SUP-B15, and of seven patients
      with Philadelphia chromosome (Ph1)-positive ALL (three of them with breakpoints
      within m-bcr) were examined. BCR-ABL fusion was detected in all cases with high
      specificity (false-positive nuclei: mean, 0.1%). On cytogenetic preparations, the
      percentages of BCR-ABL-positive interphase cells ranged from 53% to 91%.
      Comparable efficiencies were achieved on blood smears. In conclusion,
      hybridization with D107F9 and cos-abl 8 allows unambiguous diagnosis of BCR-ABL
      genes and is likely to become an important tool for the monitoring of therapies
      in patients with CML and ALL.

PMID- 8142659
TI  - Myeloperoxidase (MPO) gene mutation in hereditary MPO deficiency.
AB  - Myeloperoxidase (MPO), present in the azurophilic granules of polymorphonuclear
      leukocytes, is a myeloid enzyme whose synthesis is restricted to promyelocytes.
      Complete hereditary MPO deficiency affects 1 in 2,000 to 4,000 individuals;
      however, the genetic cause of this defect is unclear. We have determined the
      molecular basis of MPO deficiency in one individual (SQ). Granulocytes of SQ had
      no MPO activity, and had complete absence of mature and precursor MPO protein by
      Western blotting. Scanning MPO gene structure by Southern blotting detected a
      novel BgI II fragment in SQ; no other alteration in gross gene structure was
      detected. We hypothesized that a single base pair mutation formed a new BgI II
      restriction site, and that this occurred in exon 10 of MPO gene. As predicted,
      exon 10 from SQ was cleaved by BgI II, but DNA from the normal patients and five
      other MPO-deficient patients was not cleaved by this enzyme. Direct sequencing of
      the polymerase chain reaction (PCR) product of exon 10 showed a C to T
      substitution at codon 569 in exon 10, resulting in arginine (CGG) to tryptophan
      (TGG) substitution and creating a novel BgI II site. The mutation was homozygous,
      as shown by both sequencing and Southern blotting, and no other alterations in
      base sequence were detected. To determine the frequency of this mutation, DNA was
      collected from 400 normal individuals, and the presence of the mutation was
      examined by digesting with BgI II after amplifying exon 10 by PCR. No other case
      with the novel BgI II site was detected, suggesting that this is not a
      restriction fragment length polymorphism. The rest of the coding region of the
      MPO gene was sequenced in DNA from SQ, as well as from the five other MPO
      deficient individuals and one normal person; no other mutations were found. Our
      results suggest that a point mutation at codon 569 of MPO gene represents one
      molecular form of MPO deficiency.

PMID- 8142660
TI  - Contact activation triggers stimulation of the monocyte 5-lipoxygenase pathway
      via plasmin.
AB  - The purpose of this study was to characterize the stimulus that activates the 5
      lipoxygenase pathway in human peripheral monocytes (PM) during the process of
      contact activation. Incubation of PM, but not of polymorphonuclear leukocytes
      (PMN), in contact-activated, recalcified plasma induced a time-dependent release
      of leukotrienes (LT). The presence of platelets was required for the generation
      of cysteinyl-LT, but LTB4 formation also proceeded in their absence, although to
      a lesser extent. Plasmin, presumably generated via the intrinsic fibrinolytic
      pathway, was liable for the 5-lipoxygenase stimulation during contact activation
      inasmuch as (1) the 5-lipoxygenase pathway in PM was stimulated by contact
      activated, recalcified, autologous or homologous plasma, but not by factor XII
      deficient or prekallikrein-deficient plasma; (2) lysine analogs such as N alpha
      acetyl-L-lysine, 6-aminohexanoic acid (6-AHA), or trans-4-
      (aminomethyl)cyclohexane-1-carboxylic acid (t-AMCA), which inhibit plasmin(ogen)
      binding to PM plasmin(ogen) binding sites, concentration-dependently reduced the
      cysteinyl-LT release; (3) plasminogen activators such as urokinase or
      streptokinase concentration-dependently enhanced the cysteinyl-LT release up to
      10 and 1,000 IU/mL, respectively, while higher concentrations were less effective
      leading to bell-shaped concentration-response curves; (4) plasmin inhibitors such
      as aprotinin or alpha 2-antiplasmin concentration-dependently inhibited the
      cysteinyl-LT release; and (5) preincubation of plasma with monoclonal antibodies
      directed against plasminogen and capable of preventing plasminogen activation
      blocked the contact-mediated 5-lipoxygenase stimulation. Moreover, incubation of
      PM with plasmin, but not with plasma kallikrein, in Hanks' balanced salt solution
      (HBSS)-bovine serum albumin (BSA) 0.4% triggered a concentration-dependent
      release of LTB4 up to 0.1 caseinolytic units (CU)/mL, with higher concentrations
      being less effective. By contrast, release of cyclooxygenase metabolites such as
      thromboxane (TX) B2 and prostaglandin (PG) E2 was not stimulated by plasmin,
      indicating specificity for the 5-lipoxygenase pathway. With plasmin as a hitherto
      unknown stimulus of the 5-lipoxygenase pathway in PM, a novel link between
      contact activation and inflammation has been established.

PMID- 8142661
TI  - Use of recombinant human erythropoietin in allogeneic bone marrow transplant
      donor/recipient pairs.
AB  - In an attempt to reduce or eliminate homologous red blood cell transfusion
      requirements during allogeneic bone marrow transplantation (BMT), we instituted a
      novel program whereby recombinant human erythropoietin was administered to pairs
      of BMT donors and recipients. Eleven recipients and their HLA-matched donors were
      enrolled. Donors treated with recombinant human erythropoietin (rHuEPO) were
      phlebotomized a median of 6 U (range, 4 to 11 U) of blood over a 5-week period.
      This donor-derived blood was available to the BMT donor or recipient as needed.
      Transplant recipients were also treated with rHuEPO post-BMT to hasten
      erythropoiesis. Five of 11 BMT recipients underwent transplant receiving only
      donor-derived red blood cell transfusion, compared with 0 of 11 concomitant
      control recipients (P = .04). In addition, the time to absolute reticulocyte
      count > or = 10(4)/microL was statistically shorter in the rHuEPO-treated
      recipient group. This study serves as a paradigm for hematopoietic growth factor
      use in allogeneic BMT to decrease or eliminate homologous transfusion exposures
      and to possibly hasten hematopoietic engraftment.

PMID- 8142662
TI  - Effect of recombinant canine granulocyte-macrophage colony-stimulating factor on
      hematopoietic recovery after otherwise lethal total body irradiation.
AB  - Recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF)
      was studied in normal dogs and in dogs receiving otherwise lethal total body
      irradiation (TBI) without marrow transplant. Five normal dogs receiving 25
      micrograms/kg of rcGM-CSF by subcutaneous (SC) injection twice daily (BID) for 14
      days showed increases in peripheral blood neutrophil counts of three to five
      times the baseline. Platelet counts decreased during administration of rcGM-CSF
      to a mean nadir of 52,800. Ten dogs received 400 cGy TBI at 10 cGy/min from two
      opposing 60Co sources and no marrow graft. Within 2 hours of TBI, rcGM-CSF was
      begun at a dose of 50 micrograms/kg SC BID for 5 doses and then continued at 25
      micrograms/kg SC BID for 21 days. Only 1 of the 10 dogs receiving rcGM-CSF
      survived with complete and sustained recovery of hematopoiesis. One of 13
      historical control dogs survived after 400 cGy with no hematopoietic growth
      factor or marrow infusion. Results with rcGM-CSF were compared with previous and
      concurrent data with G-CSF studied in the same model. Of 10 dogs receiving G-CSF,
      8 survived with complete and sustained hematopoietic recovery, a significantly
      better survival than that seen with rcGM-CSF (P = .006). Neutrophil counts were
      sustained at higher levels after TBI for the first 18 days in the G-CSF group (P
      < .016) and the neutrophil nadirs were higher. No differences in neutrophil
      nadirs were noted between the rcGM-CSF and control groups. Dogs treated with rcGM
      CSF experienced a more rapid decline of platelet counts than G-CSF-treated or
      control dogs over the first 18 days (P < .001). The nadir of the platelet count
      was higher in the control group than in either the G-CSF or rcGM-CSF group and no
      significant difference was observed between the G-CSF and rcGM-CSF groups. After
      otherwise lethal TBI (400 cGy) in dogs, rcGM-CSF was not effective in promoting
      hematopoietic recovery or improving survival.

PMID- 8142663
TI  - Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after
      allogeneic bone marrow transplant: correlation with CMV disease and effect of
      ganciclovir prophylaxis.
AB  - Protection from cytomegalovirus (CMV) disease in immunocompromised hosts has been
      shown to correlate with recovery of the host virus-specific CD8+ T-cell response.
      The administration of ganciclovir to immunosuppressed transplant recipients as
      antiviral prophylaxis has reduced the early risk of CMV disease, but late disease
      is observed with increased frequency, suggesting that recovery of the CMV
      specific T-cell responses necessary for protective immunity may be delayed in
      these patients. Therefore, we evaluated reconstitution of CMV-specific T-cell
      responses in 47 bone marrow transplant (BMT) recipients entered on a randomized
      placebo-controlled study of ganciclovir. The study drug was initiated at a mean
      of 24 days after BMT. At day 30 to 40, a minority of patients had recovery of T
      cell immunity to CMV and the frequency of reconstitution was equivalent in
      patients randomized to ganciclovir or placebo. The failure of ganciclovir to
      effect early reconstitution may reflect the short duration of treatment. Early
      recovery was associated with the infusion of BM from a CMV seropositive donor (P
      = .07 for CD8+ cytotoxic T cell (CTL), P = .04 for CD4+ Th). Between day 40 and
      day 90, recovery of deficient CD8+ and CD4+ CMV-specific T-cell responses
      occurred in the majority of individuals that received placebo, but in a minority
      of ganciclovir recipients. Two cases of late-onset CMV disease occurred in
      ganciclovir recipients. In all patients, the presence of a CTL response to CMV
      conferred protection from subsequent CMV disease (P = .005), and these protective
      CTL responses are shown to be specific for structural virion proteins similar to
      the responses in immunocompetent CMV seropositive individuals. These data confirm
      the importance of CMV-specific T-cell responses and suggest that a delay in
      recovery of these responses as a result of ganciclovir prophylaxis may contribute
      to the occurrence of late CMV disease.

PMID- 8142664
TI  - Effect of T-cell depletion as graft-versus-host disease prophylaxis on
      engraftment, relapse, and disease-free survival in unrelated marrow
      transplantation for chronic myelogenous leukemia.
AB  - Between January 1988 and March 1993, 48 patients received T-cell-depleted marrow
      grafts from unrelated donors as treatment for chronic myelogenous leukemia (CML).
      The median age of the population was 31.7 years (range 5.4 to 53) with 17 of 48
      patients greater than 40 years of age. Twenty-seven patients were transplanted in
      chronic phase, 17 in accelerated phase, and 4 in blast crisis. All patients
      received a standardized preparative regimen of cyclophosphamide, high-dose
      cytosine arabinoside, methylprednisolone, and total body irradiation. Marrow
      grafts were depleted of mature T cells with the alpha beta T-cell receptor
      antibody T10B9 as graft-versus-host disease (GVHD) prophylaxis. All patients also
      received posttransplant cyclosporine therapy. Twenty-eight of 48 patients were
      mismatched with their donors for one or more HLA-A, B, DR, or DQ loci by either
      serology or high-resolution oligonucleotide genotyping. Nine of 28 were
      mismatched at multiple HLA loci. Durable engraftment was achieved in 94% (45/48)
      of patients. The actuarial probability of developing grades II to IV and grades
      III to IV acute GVHD were 39.6% (95% confidence interval (CI) 26.9 to 53.0) and
      8.3% (95% CI 6.1 to 10.9) for the entire cohort. There was no difference in the
      incidence of grades II to IV acute GVHD between patients receiving matched
      (36.8%) or mismatched (41.4%) marrow grafts (P = .77). The actuarial probability
      of relapse at 2 years was 8.8% (95% CI 2.1 to 21.6) for the entire cohort and 18%
      (95% CI 4 to 41) for patients transplanted in either the accelerated or blast
      crisis phase (advanced disease). One cytogenetic relapse has occurred among
      patients transplanted in the chronic phase. The probability of disease-free
      survival at 2 years was 52% (95% CI 24 to 70) for patients transplanted in
      chronic phase and 46% (95% CI 25 to 73) for patients transplanted with advanced
      disease. No difference in disease-free survival was observed between patients
      receiving matched (49%) or mismatched (51%) marrow grafts (P = .90). This study
      shows that patients receiving unrelated T-cell-depleted marrow grafts for CML can
      achieve durable engraftment with a low incidence of severe GVHD and apparent
      preservation of graft-versus-leukemia reactivity. These data also suggest that T
      cell depletion may allow patients who might otherwise experience unacceptable
      toxicity from GVHD-related complications caused by older age or increased HLA
      disparity to benefit from unrelated marrow grafts.

PMID- 8142665
TI  - Peripheral blood lymphocytes as target cells of retroviral vector-mediated gene
      transfer.
AB  - Peripheral blood lymphocytes (PBLs) are key target cells for gene therapy of a
      number of inherited and acquired blood disorders. We have systematically compared
      four retroviral vectors, designed according to different strategies, for their
      efficiency in transfer and expression in human PBLs of the same reporter gene.
      The receptor gene used in the study codes for the human low-affinity nerve growth
      factor receptor (LNGFR), and is not expressed on the majority of human
      hematopoietic cells, thus allowing quantitative analysis of the transduced gene
      expression by immunofluorescence, with single cell resolution. Peripheral blood
      mononuclear cells (PBMCs), as well as human hematopoietic cell lines of myeloid
      and lymphoid origin, were transduced with the four vectors and analyzed for
      efficiency of gene transfer, integration and stability of vector proviruses, and
      LNGFR expression at both RNA and protein level. Fluorescence-activated cell
      sorter analysis of coexpression of LNGFR and lineage-specific cell surface
      markers was performed in transduced cell lines, PBLs, and T-cell clones to study
      gene expression on specific cell subpopulations. Although crucial differences
      were observed among different constructs, all retroviral vectors could transduce,
      under appropriate infection conditions, T-cell populations representative of the
      normal immune repertoire. Gene transfer and expression could be demonstrated also
      in circulating progenitors of mature T cells. Expression of the transduced gene
      was heterogeneous among cell populations infected with the different vectors,
      with optimal results obtained by two of the four constructs. Finally, we have
      devised a simple protocol based on vector-mediated gene transfer and positive
      immunoselection of the transduced cells that produces virtually 100% gene
      modified cells. This may represent a crucial improvement in the way of designing
      efficacious protocols involving the use of gene-modified T lymphocytes in
      clinical studies.

PMID- 8142666
TI  - Pneumonia and pneumococcal immunization in human immunodeficiency virus
      seropositive hemophiliacs.

PMID- 8142667
TI  - Internucleosomal cleavage of DNA is insufficient evidence to conclude that cell
      death is apoptotic.

PMID- 8142668
TI  - Detection and viability of tumor cells in peripheral blood stem cell and bone
      marrow collections from breast cancer patients.

PMID- 8142669
TI  - Frequency of a defective response to activated protein C in patients with a
      history of venous thrombosis.

PMID- 8142670
TI  - Alteration by prolonged oral administration of a thyrotropin-releasing hormone
      analog, TA-0910, of the pituitary-thyroid axis in subjects with brain stroke.
AB  - We evaluated whether prolonged oral administration of a novel analog of
      thyrotropin-releasing hormone (TRH), TA-0910, may change the pituitary-thyroid
      axis in human subjects with brain stroke. The subjects were given one oral dose
      of 2.5-20 mg of TA-0910 daily for 8 weeks, and then blood levels of TA-0910,
      thyroid hormones and thyrotropin (TSH) were measured. Plasma levels of TA-0910
      were elevated with increasing doses. After administration of TA-0910, the basal
      levels of thyroid hormones and TSH had a tendency to increase and decrease,
      respectively, but those changes remained in the normal range. The secretion of
      TSH in response to TRH was not significantly affected by TA-0910 administration.
      No significant changes in other pituitary hormones were observed after TA-0910
      administration. The present data indicate that prolonged oral administration of
      TA-0910 did not significantly alter the pituitary-thyroid axis in subjects with
      brain stroke.

PMID- 8142671
TI  - Demonstration of the deposition of hemosiderin in the kidneys of patients with
      paroxysmal nocturnal hemoglobinuria by magnetic resonance imaging.
AB  - Hemosiderinuria caused by intravascular hemolysis is a characteristic clinical
      feature of an acquired hemolytic disorder, paroxysmal nocturnal hemoglobinuria
      (PNH). We examined the deposition of hemosiderin (iron) in the kidneys of 6
      patients with PNH using magnetic resonance imaging (MRI). Three patients with
      autoimmune hemolytic anemia (AIHA), a hemolytic disorder showing extravascular
      hemolysis, served as controls. In five of the six patients with PNH, a
      characteristic T2-weighted MRI of the kidneys, suggesting the deposition of iron
      (hemosiderin) predominantly in the renal cortex, was obtained. Hemosiderin
      deposition was not revealed in the kidneys of any of the patients with AIHA. We
      conclude that MRI is a sensitive means of detecting hemosiderin deposited in the
      renal cortex of patients with PNH and that this feature is considerably specific
      for diseases showing intravascular hemolysis, as represented by PNH.

PMID- 8142672
TI  - Effects of an angiotensin-converting enzyme inhibitor, alacepril, on
      cardiovascular and sympathetic nervous responses to mental stress in patients
      with essential hypertension.
AB  - The effects of an angiotensin-converting enzyme inhibitor, alacepril, on
      cardiovascular and plasma catecholamine responses to mental stress were studied.
      A mental arithmetic test (MAT) was carried out in 9 patients with essential
      hypertension before and after treatment with alacepril, 25 mg once daily for 2
      weeks, and in 9 age- and sex-matched normal subjects. Systolic blood pressure at
      rest and during MAT and the change in plasma norepinephrine concentrations during
      MAT were significantly greater in the hypertensive subjects than in the normal
      subjects. Alacepril significantly reduced systolic blood pressure, both at rest
      and during MAT, as compared to before treatment in the hypertensive subjects.
      Furthermore, alacepril significantly attenuated the change in plasma
      norepinephrine concentrations during MAT (from 127 +/- 76 pg/ml to 66 +/- 42
      pg/ml, p < 0.05). These results suggest that alacepril significantly suppresses
      the augmented cardiovascular and sympathetic nervous responses to mental stress
      in patients with essential hypertension.

PMID- 8142674
TI  - Effect of rush immunotherapy in house-dust-mite (HDM)-sensitive adult bronchial
      asthma: changes in in vivo and in vitro responses to HDM.
AB  - An open study was conducted to evaluate the changes in in vivo and in vitro
      responses to house-dust-mite (HDM) after rush immunotherapy (RI). A 7-day RI
      protocol using an extract containing HDM allergen was administered to 12 subjects
      with HDM-sensitive asthma, and the effects on bronchial responsiveness and serum
      antibody levels were evaluated up to 16 or 20 weeks after RI. The levels of HDM
      specific IgG, IgG1 and IgG4 antibodies were significantly elevated from 4 or 8
      weeks after RI. Provocative doses causing a 20% fall in FEV1 (PD20) by allergen
      inhalation were elevated in all subjects at 16 to 20 weeks after RI. There was a
      high correlation between the increase in log-PD20 and the increase in the ratio
      of HDM-specific IgG4 to IgG1 (r = 0.68, p < 0.05). The results suggest that RI
      elicits the improvement of allergen-specific bronchial responsiveness and the
      increase in serum antibody levels within a relatively short period.

PMID- 8142673
TI  - Suppression of secondary hyperparathyroidism in chronic dialysis patients by
      single oral weekly dose of 1,25-dihydroxycholecalciferol.
AB  - Eleven hemodialysis patients who developed refractory secondary
      hyperparathyroidism, despite conventional vitamin D therapy, were treated with
      large oral doses of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. Therapeutic
      regimen was a single oral dose of up to 8.0 micrograms administered once weekly
      following hemodialysis. A maximum serum level of 1,25(OH)2D occurred four hours
      after the 8.0 micrograms dose. A positive correlation (Y = 84.3X-22.1: P < 0.01)
      was found between the maximal serum 1,25(OH)2D concentration (Cmax) and the dose
      of 1,25(OH)2D3 when plotted on a logarithmic scale. Forty-eight hours after the
      administration of the 8.0 micrograms dose, the parathyroid hormone (PTH) level
      and the alkaline phosphatase activity (ALP) were markedly decreased without
      evidence of hypercalcemia. A significant inverse relationship was found between
      the Cmax of 1,25(OH)2D and the percent change in the PTH level measured after 48
      hours, either with carboxy-terminal (C-PTH) or the highly sensitive mid-portion
      assay (HS-PTH). From these results, the level of serum 1,25(OH)2D required to
      blunt the rise in serum PTH was 168 pg/ml and 203 pg/ml, respectively; these
      serum levels were achieved by the oral administration of doses of 6.0-8.0
      micrograms or higher. There were no adverse effects of treatment. Following this
      study, one patient was continuously treated with 8.0 micrograms of 1,25(OH)2D3
      orally once a week for 18 months. There was a therapeutic effect (as evidenced by
      PTH suppression, ALP suppression and the disappearance of subjective complaints)
      without the development of severe hypercalcemia or hyperphosphatemia. This
      treatment may help to prevent or treat secondary hyperparathyroidism in patients
      receiving long-term dialysis.

PMID- 8142675
TI  - Prevention of bacterial and fungal infections in acute leukemia patients: a new
      and potent combination of oral norfloxacin and amphotericin B.
AB  - The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B
      (AMPH-B) for prevention of infections in patients with acute leukemia being
      treated by remission-induction chemotherapy in a randomized, controlled trial was
      studied. One hundred and six consecutive, evaluable patients were randomly
      assigned to receive orally 200 mg of norfloxacin two or four times daily and 200
      mg of amphotericin B four times daily, or amphotericin B only. A smaller
      percentage of patients with bacteriologically-documented infections was observed
      in the study group compared with the control group (34.6% vs 56.9%; P < 0.05).
      The mean number of days that the patients received empirical antibiotic therapy
      was shorter in the study group (23 days vs 30 days; P < 0.05). The percentage of
      patients with a gram-negative bacterial infection (9.6% vs 27.5%; P < 0.05) or a
      fungal infection (17.3% vs 37.3%; P < 0.05) was decreased in the study group.
      This new combination antimicrobial regimen is safe and effective for prevention
      of gram-negative bacterial as well as fungal infections in patients with acute
      leukemia being treated with cytotoxic remission-induction chemotherapy.

PMID- 8142676
TI  - Emergence of acute interstitial pneumonia following high dose interferon delta
      treatment in a case of chronic myelogenous leukemia.
AB  - Here we report a 58-year-old man with chronic myelogenous leukemia in the chronic
      phase, who developed acute respiratory failure following administration of high
      dose natural interferon delta (6,300 x 10(4) units/week). Radiological and
      histological findings were consistent with acute interstitial pneumonia (AIP).
      Although the pathogenesis remains unclear, it is important to watch for the
      possible development of AIP when employing interferon delta therapy, especially
      at high doses.

PMID- 8142677
TI  - Spontaneous bacterial peritonitis in an adult patient with nephrotic syndrome.
AB  - Most cases of spontaneous bacterial peritonitis (SBP) in association with
      nephrotic syndrome are children. The complication of SBP in adults with nephrotic
      syndrome is extremely rare. Herein, we report a 25-year-old man with nephrotic
      syndrome and chronic renal failure who suffered from SBP. Citrobacter freundii
      was isolated from ascites. Irreversible deterioration of renal function followed
      the development of SBP, though the peritonitis was cured with antibiotic
      treatment. This case suggests that SBP is a rare, but serious complication of
      adult nephrotic syndrome with ascites.

PMID- 8142678
TI  - Detection of a central nervous system lesion in a patient with Fisher's syndrome.
AB  - We report a 57-year-old man with Fisher's syndrome in whom both peripheral and
      central nervous system (CNS) lesions were detected. Clinical electrophysiological
      examinations including peripheral conduction studies, SEPs and BAEPs indicated
      conduction delay in the CNS as well as in the peripheral nerve.

PMID- 8142679
TI  - Double filtration plasmapheresis in a patient with autoimmune hepatitis-systemic
      lupus erythematosus overlap.
AB  - Double filtration plasmapheresis (DFPP) therapy was administered to a patient
      with autoimmune hepatitis (AIH)-systemic lupus erythematosus overlap. The patient
      had suffered from recurrent AIH attacks with an interval of 3-4 months despite
      massive corticosteroid administration. After vigorous removal of immunoglobulins
      by DFPP procedures combined with immunosuppressive therapies, clinical and
      laboratory findings of AIH were remarkably improved. DFPP might be an optional
      modality in the treatment of AIH patients, especially for those who are resistant
      to and/or cannot tolerate massive corticosteroid or immunosuppressive therapies.

PMID- 8142680
TI  - Adult Still's disease with Sjogren's syndrome successfully treated with
      intravenous pulse methylprednisolone and oral cyclophosphamide.
AB  - A patient with adult Still's disease and Sjogren's syndrome failed to respond to
      conventional doses of corticosteroids. Therefore intravenous pulse
      methylprednisolone combined with oral cyclophosphamide was given which
      subsequently resolved the flare of rashes, fevers, and arthritis. This
      combination therapy may be a useful therapy to consider in patients with adult
      Still's disease who are resistant to conventional treatment and may allow a
      reduction in daily corticosteroid requirement.

PMID- 8142681
TI  - Disseminated pancreatic polypeptidioma.
AB  - Pancreatic polypeptidioma, a pancreatic endocrine tumor, is an extremely uncommon
      disease and its clinical features and responses to therapy are not well known. We
      present a 33-year-old woman with disseminated pancreatic polypeptidioma, who
      subsequently showed various signs and symptoms of metastases, including bone
      pain, cranial nerve palsy, spinal block, and hematuria, and died 22 months after
      the presentation. Responses to various therapeutic regimens including hepatic
      arterial embolization, radiation therapy, systemic chemotherapy, and
      administration of interferon-alpha or somatostatin analogue, are discussed.
      Particular note in this case is a prompt response of bone metastases to the
      radiotherapy.

PMID- 8142682
TI  - Glomerulocystic kidney--report of an adult case.
AB  - A 32-year-old adult case of glomerulocystic kidney disease (GCK) is reported. He
      had brain and muscle atrophy, probably due to congenital malformation.
      Progressive renal failure developed and he died. Autopsy disclosed multiple tiny
      cysts exclusively in the renal cortices. Microscopic study revealed that the
      cysts were dilated Bowman's spaces. This case is the 12th adult case reported in
      the world.

PMID- 8142683
TI  - Isolated angiitis of the central nervous system first presenting as intracranial
      hemorrhage during cesarean section.
AB  - A case of isolated angiitis of the central nervous system (CNS) which first
      presented as intracranial hemorrhage during cesarean section is reported. Only
      one case of isolated angiitis of the CNS in post partum has been reported to
      date. Although a headache in labor and puerperium usually suggests subarachnoid
      hemorrhage, isolated angiitis of the CNS should be considered in the differential
      diagnosis.

PMID- 8142684
TI  - Successful treatment of refractory polymyositis with pulse intravenous
      cyclophosphamide and low-dose weekly oral methotrexate therapy.
AB  - A 36-year-old woman gradually developed dysphagia and muscle weakness of the
      lower extremities. Diagnosis of polymyositis was given from elevation of serum
      creatine kinase and pathological findings of a muscle biopsy. Despite oral
      prednisolone and intravenous pulse methylprednisolone therapy, her muscle
      weakness persisted, and then pulse intravenous cyclophosphamide (IVCY) therapy
      was initiated and repeated five times in total, which resulted in significant
      improvement in muscle strength. Thereafter, weekly administration of methotrexate
      at low dosage further normalized the serum creatine kinase level. We may conclude
      that IVCY and low-dose weekly methotrexate together could be an alternative in
      refractory polymyositis.

PMID- 8142685
TI  - Ethical issues of work experience.
AB  - An article appeared in this journal some months ago in which a sixteen year old
      described her 'work experience' in the operating department. In this instance it
      was a well planned, well supported experience. It is an increasingly common
      experience for managers to be asked to allow sixteen year olds to gain work
      experience in an area in which the young person has expressed an interest for a
      future career. Many people may have felt, following this confident and amusing
      article, that their concerns were unjustified. However, Angela Devine, in a
      letter published in the January 1994 issue raised some ethical questions and
      suggested that allowing sixteen year olds into the operating department during
      surgery could violate the provider/client relationship in which we stand to our
      patients.

PMID- 8142686
TI  - Laughing gas. No laughing matter.

PMID- 8142687
TI  - Scaling the patient's temperature--Part 1.
AB  - Many investigators have looked at the loss of body heat by the patient during the
      perioperative period. However the problem still remains of identifying those at
      risk using a scientific approach. This small study has looked at nine factors
      identified from a literature search, tested each against a group of 27 patients
      and then created and tested a check list and rating scale of risk for use by
      theatre nurses at preoperative assessment during a ward visit. The factors
      identified from the literature were: patient age, build and debility; the length,
      grade and site of the surgery; the type of anaesthetic used; whether cold fluids
      would be infused or used as irrigation of the wound; and the ambient temperature
      during surgery. Each of these factors were tested against temperature loss and
      the results indicate that each factor alone does not influence patient
      temperature loss [P = > 0.05] but that a combination of factors in degrees of
      severity do. Moreover, the patient's preoperative haemoglobin level also appears
      to influence the degree of heat loss [P = < 0.05]. The study also looked at the
      level of success achieved by the theatre nurses in identifying the levels of each
      factor and this showed that the nurses could identify each level with a 77%
      success rate overall. After constructing a scale it was tested against the data
      and this showed that the Rating Scale could identify those at risk [P = <
      0.005].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142688
TI  - The National Breast Implant Registry.

PMID- 8142689
TI  - Silicone gel breast implants.

PMID- 8142690
TI  - African diary.

PMID- 8142691
TI  - History of anaesthesia.
AB  - 1846 was a good year for patients. While there is debate on exactly who gave the
      first anaesthetic, there is no doubt that ether was the initial agent used and
      that the era of painless surgery was born in 1846.

PMID- 8142692
TI  - The development of anaesthetic and recovery nurse education.
AB  - The development of education for anaesthetic and recovery nurses is a relatively
      recent concept. Until the mid 1980s, anaesthetic and recovery nursing education
      in Britain was seen as an integral part of theatre nursing. Therefore, in order
      to trace the developments in anaesthetic and recovery nursing, it is necessary to
      explore the development of the role of the nurse in theatre.

PMID- 8142693
TI  - Pain--patients in control. An evaluation of PCA.

PMID- 8142694
TI  - On the origin and dynamics of the vasomotion of small arteries.
AB  - A system of differential equations describing stationary vasomotion is
      formulated. It incorporates the ionic transports, cell-membrane potential, muscle
      contraction of the vessel smooth muscle cells, and the mechanics of a thick
      walled cylinder. It is shown that the interaction of Ca2+ and K+ fluxes mediated
      by voltage-gated and voltage-calcium-gated channels, respectively, brings about
      periodicity of those transports. This results on a time-periodic cytoplasmic
      calcium concentration, myosin light chains phosphorylation, and crossbridges
      formation with the attending muscle stress. The vessel's transmural pressure
      determines a hoop stress. The resultant hoop, elastic, and muscle stresses
      determine the rate of change of the vessel's diameter: vasomotion. The model
      results agree with the experimental observations. The sensitivity of the
      vasomotion's dependence on parameter values and its significance to experimental
      protocols are examined. Further, it is hypothesized that the dependence of
      calcium-channel openings on voltage is shifted by changes on transmural pressure.
      Thus, Harder's experimental results are reproduced, among them the decreasing of
      vessel diameter with increasing pressure. Those behaviors are associated with a
      pattern of change of the singularities of the system of equations describing the
      model. This suggests a functional relationship on the interactions of Ca2+ and K+
      fluxes responsible for the myogenic response; it may not result from a single
      molecular mechanism. The model is constructed so that additional experimental
      information can be readily incorporated.

PMID- 8142695
TI  - Study of propagation along nonuniform excitable fibers.
AB  - Two related reaction diffusion systems that support traveling wave solutions when
      parameters are constant are studied when there are jump discontinuities in the
      diffusion coefficient. The first system represents a classical axon model where
      the fiber had a jump in diameter at discrete locations and the membrane dynamics
      represent those of barnacle muscle (which we call Morris-Lecar dynamics). The
      second model represents a passive cable with a uniform density of spines that
      have Morris-Lecar dynamics. Conditions under which echo waves form are studied,
      as well as conditions when wave blocking takes place with a thickening of the
      fiber.

PMID- 8142696
TI  - A transmission model for HIV with application to the Australian epidemic.
AB  - An age-specific transmission model is proposed to describe the spread of HIV in a
      homosexual population. The model incorporates developments in the treatment of
      patients and the change in the surveillance definition of AIDS. The model is
      applied to the Australian epidemic with the aim of determining the extent of
      behavioral changes during the epidemic and assessing the extent to which therapy
      has changed the course of the epidemic. It is found that therapy and the adoption
      of totally safe sex practices by individuals who have tested HIV positive cannot
      explain the recent downturn in the rate of increase of observed AIDS incidence. A
      significant change in behavior within the general homosexual community is
      indicated.

PMID- 8142697
TI  - Quiescence and transient growth dynamics in chemostat models.
AB  - A chemostat model for microbial growth taking into account that cells can exist
      in two states, active and quiescent, is proposed and analyzed. Cells adapt to
      environmental (nutrient supply) fluctuations by changing from one state to
      another with asymmetric thresholds. Depending on the growth conditions, steady
      state growth is attained with either a homogeneous population of active cells or
      a heterogeneous population of both active and quiescent cells. Transient
      oscillatory growth that has been observed in bacterial and algal chemostat
      cultures can be a result of such an adaptation mechanism.

PMID- 8142698
TI  - A mathematical model that mimics the bursting oscillations in pancreatic beta
      cells.
AB  - A revised version of Rossler's dual principle is used to realize a geometrical
      mechanism for chaos generation. The resulting mathematical model is a singularly
      perturbed system with three time scales. The system is then used to mimic the
      glucose-induced electrical activity of pancreatic beta-cells.

PMID- 8142699
TI  - Interpretation of ultrastructural changes in Cladophora glomerata resulting from
      hyamine toxicity.

PMID- 8142700
TI  - Differential response of green algal species to solvents.

PMID- 8142701
TI  - Effects of cadmium, naphthalene, and DDVP on gut carbohydrases activity in bream
      (Abramis brama L.) and Mozambique tilapia (Oreochromis mossambicus Peters).

PMID- 8142702
TI  - Acute toxicity of nifurpirinol, a fish chemotherapeutant, to milkfish (Chanos
      chanos) fingerlings.

PMID- 8142703
TI  - Acute toxicity of deltamethrin and dieldrin to Oreochromis niloticus (LIN).

PMID- 8142704
TI  - Behavioral responses of juvenile coho salmon (Oncorhynchus kisutch) exposed to
      pulp mill effluents.

PMID- 8142705
TI  - Parathion effect on acetylcholinesterase from fish through an artificial trophic
      chain: Ankistrodesmus falcatus-Moina macrocopa-Oreochromis hornorum.

PMID- 8142706
TI  - Effects of in vitro nickel exposure on the macrophage-mediated immune functions
      of rainbow trout (Oncorhynchus mykiss).

PMID- 8142707
TI  - Distribution of metals in some fishes from Santa Cruz de Tenerife, Canary
      Islands.

PMID- 8142708
TI  - Metals in sediments of San Andres Lagoon, Tamaulipas, Mexico.

PMID- 8142709
TI  - Tolerance of Nitrobacter to toxicity of some Nigerian crude oils.

PMID- 8142710
TI  - Aluminium dissolved from kitchen utensils.

PMID- 8142712
TI  - Persistence and leaching of the herbicide imazapyr in soil.

PMID- 8142711
TI  - Organochlorine pesticides and PCBs in human adipose tissues in Poland.

PMID- 8142713
TI  - Trihalomethanes in water supplies in the San Sebastian area, Spain.

PMID- 8142714
TI  - Determination of fenitrothion and diazinon in air.

PMID- 8142715
TI  - Chlorpyrifos, ethion, fenitrothion, and methidathion residues in chickens.

PMID- 8142716
TI  - Acceleration of paraquat adsorption onto chitosan by the presence of sodium
      chloride.

PMID- 8142717
TI  - Reduction of manganese accumulation by ethylenediamine tetraacetic acid and
      nitrilo triacetic acid in okra (Abelmoschus esculentus L.) grown in sewage
      irrigated soil.

PMID- 8142718
TI  - Effect of acidification on metal uptake of Picea abies seedlings.

PMID- 8142719
TI  - Effect of Pb, Cd, Hg, As, and Cr on germination and root growth of Sinapis alba
      seeds.

PMID- 8142720
TI  - Modification of genetic damage by dihomo-gamma-linolenic acid.

PMID- 8142721
TI  - In vitro cutaneous metabolism of DDT in human and animal skins.

PMID- 8142722
TI  - Spinal cord injuries: aspects of psychological care.
AB  - Spinal cord injury is one of the most life-changing injuries a person can
      sustain. This article explores some aspects of the psychological impact of the
      acute stage of such injury and examines the nurse's role in providing initial
      psychological support.

PMID- 8142723
TI  - Service users' views of psychiatric nurses.
AB  - With the shifting emphasis in the NHS towards quality assurance and consumerism,
      user satisfaction has become an important issue for mental health nurses to
      consider. This article provides some data from a survey of 516 psychiatric
      patients conducted by the authors on behalf of national MIND in 1990.

PMID- 8142724
TI  - Development of a training programme for triage nursing.
AB  - This article describes the preparation and development of a training programme to
      prepare staff for the implementation of triage nursing. It outlines the essential
      training needs for this complex role and the use of multidisciplinary group work
      and experiential learning to promote good communication and holistic
      individualized patient care.

PMID- 8142725
TI  - Clinical supervision and primary nursing.
AB  - To enable primary nursing to function effectively there is a need for a process
      of clinical supervision. This article defines the concept of clinical
      supervision, describes how it can be implemented and discusses who will carry it
      out.

PMID- 8142726
TI  - Bleak prospects for nurses in 1994.

PMID- 8142727
TI  - Nurses should work more closely with consumer organizations.

PMID- 8142728
TI  - Views of two consumer representatives of the UKCC.

PMID- 8142729
TI  - Nurse-aid management of psychiatric emergencies: 1.
AB  - Most nurses, irrespective of specialty, will be confronted with disturbed
      psychiatric patients. There are many forms of psychiatric emergency; this article
      examines nurse-aid management of acute confusional states, hallucinations,
      delusional thinking and suspiciousness and highlights interventions aimed at
      dealing with disturbed patients to avoid an immediate deterioration of the
      situation.

PMID- 8142730
TI  - Stuck in a time warp: communication between hospitals and patients.

PMID- 8142731
TI  - Patient advocacy in palliative care.
AB  - Advocacy is a contentious and topical issue and there is continued debate as to
      whether a nurse can ever truly represent patients' views and interests. This
      article will address this argument with particular reference to palliative care.

PMID- 8142732
TI  - Doctors in management.
AB  - The involvement of clinicians in management is a key issue in the future of
      health care provision in the UK. This article examines the advantages and
      disadvantages of doctors combining their clinical role with managerial
      responsibilities.

PMID- 8142733
TI  - History and evolution of stomas.
AB  - This article, describes the evolution of stoma formation from earliest times to
      current innovative procedures. Surgeons are continually trying to develop new
      procedures so that they can offer less socially incapacitating alternatives to
      the abdominal stoma.

PMID- 8142734
TI  - [Risks of infection caused by blood and blood products with reference to the so
      called AIDS scandal].

PMID- 8142735
TI  - [Autologous blood donation and isovolemic hemodilution--indications and practical
      implementation].
AB  - OBJECTIVE: The state of the art of autologous blood transfusion is described with
      special emphasis on safety aspects, indications and medicolegal implications.
      DATA SOURCES AND SELECTION CRITERIA: Literature was retrieved using the MEDLINE
      literature database. Medical and legal expert opinions on autologous blood
      transfusion programmes are presented as well as the actual German jurisdiction.
      Guidelines for autologous predeposit and haemodilution used in the University of
      Munster are described. RESULTS: In the past decade all forms of autologous
      transfusions gained increasing influence in haemotherapy due to the ongoing
      discussion on the safety of blood products. The German Federal Court has demanded
      that whenever homologous perioperative transfusion is considered likely, patients
      have to be offered autologous predeposit. Legal conditions for autologous
      programmes directed by anaesthetists not specialised in transfusion medicine are
      described. Whole-blood predeposit should be limited to two autologous units. In
      cases with minor blood loss, isovolaemic haemodilution may be performed instead
      of autologous predeposit. However, autologous transfusions have their specific
      risks that are either related to the patient or to the procedure of autologous
      predeposit, e.g., clerical error, contamination of blood products and technical
      faults. Standard procedures of the University of Munster to ensure low-risk
      autologous transfusion are presented. They consist in adequate handling and
      proper identification, testing of donor for virus infection markers, bacterial
      culture from blood products and a list of contraindications: anaemia, unstable
      angina, myocardial infarction within 3 months, decompensated heart insufficiency,
      aortic valve stenosis with angina, and cases with infection and fever.
      CONCLUSION: The risks related with autologous transfusion should be lower
      compared to homologous transfusions. Well-defined standards concerning
      indications and techniques are required to reach this goal.

PMID- 8142736
TI  - Current problems with autologous blood supply.
AB  - OBJECTIVE: The purpose of the present study consists in an updated review of
      recent progress in the field of autologous blood supply. At different medical
      centers, autologous blood products are collected by quite different procedures,
      which may be applied during pre-, intra- and/or postoperative periods according
      the technical possibilities of the local blood supply systems. The products are
      very different, consisting in whole blood, red cell concentrates, platelet
      concentrates, fresh-frozen plasma (from whole blood and from plasmapheresis), as
      well as in wound and drainage fluid and in washed red cell concentrates. Iron
      therapy against autologous blood donation--or against surgical bleeding-induced
      anemia--is now well established, but it is unclear whether it should be given
      perorally or intravenously. In addition, erythropoietin substitution may be
      necessary for some but not all patients. DATA SOURCES: For our review we have
      used as sources, beyond our own published reports, studies devoted to clinical
      experience as well as to pathophysiological aspects of blood donation. RESULTS
      AND CONCLUSIONS: It becomes apparent that the practice of autologous blood supply
      has now reached peripheral hospitals not affiliated with bigger medical centers.
      Smaller hospitals may share expensive equipment necessary for autologous blood
      collection. Such progress contrasts with persistent uncertainties regarding iron
      and erythropoietin substitution.

PMID- 8142737
TI  - [Monoclonal antibodies in blood group serology. Part 1: Technique of production,
      ABO and Lewis system].
AB  - OBJECTIVE: The introduction of monoclonal antibodies in routine blood group
      typing has also given rise to new findings. This paper was designed to
      demonstrate and clarify modifications relevant in practice. SOURCES: Our own
      experience in the production and application of monoclonal antibodies as well as
      the relevant literature are taken into consideration. RESULTS: The development
      and production of murine and human monoclonal antibodies is described especially
      regarding the selection and the safety of clones. An update of the availability
      and use of monoclonal antibodies in respect to the different blood group systems
      is given, with special reference to new findings like the A1(B) and B(A)
      phenomena. CONCLUSION: The application of monoclonal antibodies in blood group
      serology has improved the detection of weak variants and the availability of
      these reagents in general. Further improvements in this technology will make
      monoclonal antibodies also available for other blood group systems.

PMID- 8142738
TI  - [Monoclonal antibodies in blood group serology. Part 2: MNS, Rh and other blood
      group systems].
AB  - OBJECTIVE: The introduction of monoclonal antibodies in routine blood group
      typing has also given rise to new findings. This paper was designed to
      demonstrate and clarify modifications relevant in practice. SOURCES: Our own
      experience in the production and application of monoclonal antibodies as well as
      the relevant literature are taken into consideration. RESULTS: The development
      and production of murine and human monoclonal antibodies is described especially
      regarding the selection and the safety of clones. An update of availability and
      use of monoclonal antibodies in respect to the different blood group systems is
      given, with special reference to the reactivity of these new reagents with weak D
      positive (Du) red blood cells. CONCLUSION: The application of monoclonal
      antibodies in blood group serology has improved the detection of weak variants
      and the availability of these reagents in general. Further improvements in this
      technology will make monoclonal antibodies also available for other blood group
      systems.

PMID- 8142740
TI  - [Value of genetic techniques in transfusion medicine].

PMID- 8142739
TI  - [Biotest position on HIV-1 seroconversions in 1990 in 11 patients, treated with
      beta-propiolactone/uv virus inactivated PPSB].

PMID- 8142741
TI  - Retinal detachment after cataract surgery: retrospective study of 57 cases.
AB  - The Authors studied the characteristics and the surgical results of 57
      pseudophakic patients operated on between January 1989 and June 1991 for primary
      retinal detachment at the Department of Ophthalmology of the "Hotel Dieu de Paris
      Hospital", with a postoperative follow-up of at least six months. The series
      included 23 eyes with posterior chamber IOL, 33 eyes with anterior chamber IOL.
      The ECCE with PC IOL group and the ICCE with AC IOL group had the same anatomical
      and visual prognosis.

PMID- 8142742
TI  - Malignant melanoma of the iris. A 25-year analysis of Danish cases.
AB  - This study examined malignant melanoma of the iris in Denmark over a 25-year
      period on the basis of the files of the Eye Pathology Institute. From 1961 to
      1985 a total of 80 cases were found (41 males, 39 females; median age 53 years,
      range 8-83). This means an average of 3.2 cases/year with an average population
      of 4.9 million. In contrast to malignant melanoma of the choroid, an increase was
      observed. The reason is not known, although exposure to actinic rays may be a
      factor. More than a third of cases were close to the pupil, a little less than a
      third invaded the chamber angle/ciliary body. Ten cases were ring melanomas. Half
      of the tumours were spindle-celled, a quarter mixed and a few epithelioid or
      naevoid in cell morphology. Iridectomy was performed in 28 cases, primary
      enucleation in 27 and secondary enucleation in ten. Iridocyclectomy was performed
      in 15 cases. All patients could be traced. At the date of follow-up (Dec. 1,
      1991) eight had died with metastases; four of these were patients with ring
      melanoma and four with tumours invading the ciliary body. After iridocyclectomy,
      only one metastatic death was recorded--a case of incomplete resection. The grave
      prognosis of a ring melanoma is highlighted.

PMID- 8142743
TI  - Accuracy of the potential acuity meter in predicting the visual outcome in cases
      of cataract associated with macular degeneration.
AB  - In order to ascertain the accuracy and specificity of the Potential Acuity Meter
      (PAM) in the preoperative evaluation of likely postoperative visual acuity in
      cases of cataract associated with age-related macular degeneration (ARMD), we
      studied the results in 130 cases, 54 of whom had preoperatively proved or
      suspected ARMD associated with a cataract. All of them were operated with
      extracapsular extraction and implantation of an intraocular lens (IOL), and final
      visual acuity was established when all the patients were visited three months
      postoperatively. A positive linear correlation was found between normal ocular
      fundus and PAM prediction (r = 0.77), and in the group of patients with
      preoperatively confirmed ARMD (r = 0.77). No difference was found between the
      preoperative PAM estimation and the final visual acuity in both groups. The PAM
      prediction was less accurate in cases with doubtful preoperative ARMD (r = 0.58)
      for whom showed PAM the highest score of false negatives in favor of the final
      visual acuity. Our results show that PAM is a reliable clinical technique for the
      prediction of visual results after cataract surgery in cases with preoperatively
      proved or doubtful macular pathology. To the best of our knowledge, this is the
      first report regarding the sensitivity and specificity of the PAM in diseased or
      suspicious maculas associated with cataract.

PMID- 8142744
TI  - Treatment of retinal detachment with giant tear by pneumatic retinopexy.
AB  - Nine eyes suffering from retinal detachment with giant tear were treated
      successfully by pneumatic retinopexy, followed by conventional buckling
      procedures and cryopexy. The retina in six of the nine eyes reattached after
      initial operation, whereas two required additional injection of SF6 gas. The
      remaining eye, having developed low-grade proliferative vitreoretinopathy (PVR
      C1), was treated successfully with vitrectomy. Visual outcome was rather poor
      immediately after the procedures due to vitreous opacity caused by gas injection.
      However, all cases showed excellent visual acuity five months after surgery.
      Visual field examined in six cases after surgery showed no significant
      constriction. If the retinal flap is mobile, pneumatic retinopexy may be
      effective in treating retinal detachment with giant tear.

PMID- 8142745
TI  - Diabetic retinopathy and metabolic control.
AB  - Retinopathy is probably the first long-term complication of diabetes mellitus to
      become clinically evident, possibly because the retina is the only microvascular
      bed that can be observed directly and repeatedly. This makes it a good model for
      studying the pathogenesis and natural history of diabetic microangiopathy. Most
      of the proposals to account for its pathogenesis invoke mechanisms that depend
      directly on the circulating and tissue levels of glucose: protein glycosylation,
      activation of the "polyol pathway", abnormalities of vascular endothelium,
      altered capillary blood flow. Several population studies and clinical trials
      suggest that the degree of metabolic control maintained over the years influences
      the rates of appearance and progression of retinopathy. However, on an individual
      basis, factors independent of control may intervene, making some patients more or
      less prone to this complication. Animal models also suggest that the progression
      of retinopathy may become irreversible from its very early stages. From a
      clinical point of view, it is difficult to establish a satisfactory definition of
      "good" control and approaching it may increase the risk of dangerous hypoglycemia
      and weight gain. Diabetes and eye specialists are thus left to strive for the
      best possible, sensible, metabolic control but must also rely on early diagnosis
      and treatment for the sight-threatening complications of diabetes.

PMID- 8142746
TI  - Change of retinal correspondence in monocularly reduced intensity of stimulus.
AB  - We analyzed the retinal correspondence with a phase difference haploscope on
      reducing the stimulus intensity of a monocular image with a series of neutral
      density filters. Ninety-one exotropes were examined by this method. Five cases
      changed from normal to anomalous correspondence when the stimulation of the
      strabismic eye was reduced. Two cases showed anomalous correspondence without a
      filter, but normal correspondence with a reduced stimulus of the normal eye. All
      these seven cases showed normal correspondence with any other test. The results
      suggest that masked anomalous correspondence becomes manifest in some cases when
      the strabismic eye is stimulated more intensely than the normal eye. These cases
      display both normal and anomalous correspondence and this condition may be called
      dual correspondence.

PMID- 8142747
TI  - Bilateral optic neuropathy associated with the crest variant of scleroderma.
AB  - We report a case of bilateral optic neuropathy associated with the CREST
      syndrome, a variant of scleroderma. Immunosuppressive therapy achieved
      significant improvement of the visual symptoms for two years. The
      pathophysiological mechanisms underlying this unique association remain unclear.

PMID- 8142748
TI  - Idiopathic canthaxanthine retinopathy.
AB  - An unusual case of canthaxanthine retinopathy is described. The usual
      aetiological factors were absent, ingested dietary canthaxanthine is implicated
      as a possible cause.

PMID- 8142749
TI  - [The possibilities of improving the serological diagnosis of active tuberculosis
      by using the technics of immunofluorescence and ELISA].
AB  - A group of 188 adult subjects has been studied as follows: 119 cases of pulmonary
      tb confirmed by smear and/or culture; 44 cases with other chronic lung diseases;
      25 healthy persons. The following serological tests have been performed:
      immunofluorescence indirect test (FA) using mycobacterial total antigen; ELISA
      test using two antigens: PPD and a freeze dried crude sonicated extract from
      H37Rv strain (antigen "Prague"). The results show: sensitivity 77% for FA and 71%
      for ELISA; specificity 81% for FA and 86% for ELISA. If all positive results (to
      one or both tests) are being considered the sensitivity increases to 81% but
      specificity decreases to 77%. The ELISA test with both antigens succeeds in a
      good discrimination between lung active tb on one side and lung non-tb cases and
      healthy persons on the other side (p < 0.001). Using comparatively the two
      antigens in ELISA test a higher serological confirmation of active tb is reached
      with "Prague" antigen: 72.7% vs 62.8% with PPD (p < 0.025).

PMID- 8142750
TI  - [A trial of long-term home oxygen therapy in Romania (preliminary study)].
AB  - The study followed up the reliability of some French oxygen extractors of BRIOX
      type (Pierre Medical) and the advantages of long course oxygen therapy at home in
      chronic respiratory failure subjects. The study extended to a 6-8 months period
      on 4 subjects suffering from chronic obstructive lung disease dependent on oxygen
      with PaO2 of 55-60 mmHg which were given 2-2.5 l/min O2 during 15 hours/day. The
      favorable evolution and the difficulties met confirmed the efficacy and
      advantages of the method.

PMID- 8142751
TI  - [Effectiveness of salbutamol powder (Ventodisk Glaxo) compared to dosed aerosols
      (sultanol)].
AB  - The study deals with the effect of salbutamol powder (Ventodisk) administered
      with Diskhaler device comparatively to salbutamol dosed aerosols. The analysis of
      PEF variations on morning and evening in a group of patients unable to use
      correctly the dosed aerosols leads to the conclusion that salbutamol powder
      succeeds in a higher effect since the administration by Diskhaler is far easier.

PMID- 8142752
TI  - [Clinico-functional changes during inhalational corticotherapy (beclomethasone
      dipropionate) in children with severe forms of bronchial asthma].
AB  - In 14 children with corticoid-dependent severe forms of bronchial asthma, inhaled
      corticotherapy with beclomethasone dipropionate (BDP) was administered for 6
      months. Pulmonary functional investigations were performed before, at 1 as well
      as 6 months from treatment start. Functional pulmonary tests included lung volume
      and flow measurements. The results showed a remarkable improvement of the mean
      percentage values of tested functional parameters, and even a significant
      percentage of normalization concerning the same parameters (excepting MEF50)
      after 6 months of treatment.

PMID- 8142753
TI  - [Tuberculosis in the elderly: sociomedical aspects].
AB  - A study on a group of 100 tb patients aged over 60 years registered between 1987
      1991 in the district 4 of Bucharest has been carried out aiming at the evaluation
      of medical and social aspects. In order to increase the relevance of the obtained
      data, these were compared with a group of young tb patients aged 20-39 years, in
      the same territory and period of time. The results show: the case-finding
      predominantly passive, extrarespiratory forms in 25%, high contamination risk
      (63% acid fast bacilli eliminators on microscopy) non-compliance to treatment in
      1/5 of cases. These aspects could be explained by psychic particular features in
      aged persons, associated diseases a.s.o., leading to treatment failures. The
      analysis of social and epidemiological aspects of tb in aged subjects evidences
      some lack of good results in this important public health problem of people.

PMID- 8142754
TI  - [AIDS and tuberculosis. Epidemiologic aspects. Etiopathogenic correlations].

PMID- 8142755
TI  - [Sleep apnea syndrome].

PMID- 8142756
TI  - [Pulmonary alveolar proteinosis].

PMID- 8142757
TI  - [Clinico-radiologic and morphopathologic aspects of mediastinal-pulmonary
      hemangiopericytoma].
AB  - The paper points out the diagnosis of intrathoracic hemangiopericytoma in 13
      patients in the "M.Nasta" Institute of Pneumophthisiology, a seldom seen disease
      considered quite serious because of its malignant form and its late finding out.
      This is due to its non-distinctive, small number of symptoms, which has a
      negative influence upon the disease prognosis and evolution.

PMID- 8142758
TI  - [Tuberculosis treatment. II. Elements of the National Program of Antitubercular
      Chemotherapy in Romania].

PMID- 8142759
TI  - [The place of desensitization in chronic asthma].

PMID- 8142760
TI  - [The advantage of and strategy for eliminating household allergens in pediatric
      asthma].

PMID- 8142761
TI  - [Can smoking be stopped?].

PMID- 8142762
TI  - [Errors committed in using dosed aerosols in patients with obstructive lesions].
AB  - Errors committed in applying dosed aerosols in 100 patients were registered. Some
      criteria of correct technique being established, it was found out that more than
      73% of the patients committed at least one error. The non-synchronization between
      inspiration and inhaler activation, considered as the most severe error, was met
      in 52% of cases, 14% of the patients being unable to do it even after repeated
      training. The importance of a refreshing instruction of patients, concerning the
      technique and advantages in using the expansion chambers and the conditioning as
      powders of inhaling drugs, are discussed.

PMID- 8142763
TI  - [Update on bronchopulmonary cancer].

PMID- 8142764
TI  - [From the past of phthisiology (Stefan Irimescu)].

PMID- 8142765
TI  - [Beclomet and cromolyn--two therapeutical certitudes].

PMID- 8142766
TI  - Public health principles and methods.
AB  - Author presents his views on the past and present problems of public health.
      Special attention is given to the differences in public health goals of
      industrialized and developing countries.

PMID- 8142767
TI  - Ludwik Rajchman--international health leader.
AB  - Ludwik Rajchman was a man caught up in the whirlwind of international politics.
      He suffered from the conquest of his country, Poland, by both Nazism and
      Communism yet managed to rise to eminence as a leader of the Health Organisation
      of the League of Nations and then of UNICEF.

PMID- 8142768
TI  - Current principles of hygienic standards setting (Part II).
AB  - The paper presents general principles of setting the hygienic standards for
      substances of threshold effect and nonthreshold agents. The authors introduced
      the mathematical models used for quantitative risk assessment and models for
      assessment of the dose-response relationship according to the physiological
      principles.

PMID- 8142769
TI  - Biological accounts emerging from some kinds of electromagnetic waves in the
      environment.
AB  - Industrial use of induction heaters generating electromagnetic energy of
      frequencies below 9 kHz makes an exposure of their operators to magnetic field H
      of high intensity and to electric field E of relatively low intensity. The
      operators of such heaters have suffered repeatedly from infections in the upper
      respiratory tract and in the skin of the forearm. The experimental exposure of
      rats to E or H fields of frequencies of 10 Hz, 50 Hz or 1-45 kHz induced changes
      in growth rate of exposed animals and weight changes in the pituitary-adrenal
      glands. These results support the suggestion about the involvement of the
      endocrine system in the biological reaction to incident electromagnetic fields of
      VLF and ELF.

PMID- 8142770
TI  - X-ray diagnostics in Poland--doses and risks.
AB  - This article refers to radiation risk resulting from X-ray diagnostics in the
      Polish population. Frequency of the examinations were reviewed on the basis of
      data from the national survey performed in 1986. The doses to patients at
      different age were evaluated taking into consideration the exposure parameters
      really used during particular examinations. The mean effective dose for a
      statistical patient in Poland was found to be 2.8 mSv. This denotes that all X
      ray diagnostic examinations yield the mean effective dose of 1.6 mSv per capita,
      i.e. more than 60% of mean effective dose from natural background radiation.

PMID- 8142771
TI  - Assessment of the nasal mucosa in workers exposed to the prolonged effect of
      phosphorite and apatite dusts.
AB  - One hundred and thirty one workers occupationally exposed to phosphorite and
      apatite dusts and a control group underwent repeated laryngological and
      cytological examinations of nasal mucosa smears. The clinical examination showed
      chronic simple or atrophic rhinitis. The cytological test revealed metaplasia of
      the respiratory epithelium towards squamous epithelium in all smears. Both the
      rate of catarrhal changes and the degree of epithelial metaplasia varied with the
      duration of exposure.

PMID- 8142772
TI  - The relationship between ciliary muscle fatigue and the type of artificial light
      used to illuminate the area of visual work.
AB  - The relationship between the degree of eye fatigue resulting from visual work and
      type of light source used to illuminate the field of work was assessed. The tests
      were performed using artificial light sources: fluorescent lamps, incandescent
      lamps, high pressure mercury (vapour) and high pressure sodium (vapour) lamps.
      The assessment was performed on two groups of 10 women each, of which one
      included women without, and the other with, refraction errors. On the basis of
      changes of nearer vision point and dispersing lens tolerance, it was found that
      sodium light produced the highest visual fatigue in the test women, especially in
      those with refraction errors.

PMID- 8142773
TI  - Industrial evaluation of "Hygitest" detector tubes for ethyl acetate.
AB  - "Hygitest" detector tubes for ethyl acetate based on a silica gel carrier treated
      with an indicator reagent--chromium-sulphuric acid were developed. Their quality
      parameters were compared with the characteristics of the detector tubes for ethyl
      acetate produced by other companies. An evaluation of the developed detector
      tubes in industrial atmosphere was carried out. The results obtained are
      discussed in view of the non-specificity of the detector tubes proposed.

PMID- 8142774
TI  - Occupational diseases in Poland during the years 1984-1992.
AB  - The authors present the results of analysis of data on occupational diseases in
      Poland during the years 1984-1992. The statistical material covers 86,871 cases
      of various diseases. Among them hearing lesions, vocal organ diseases, contagious
      and invasive diseases, pneumoconioses, dermatoses, vibration syndrome, poisonings
      and chronic bronchitis proved to be most common. In Poland, among the etiological
      factors, noise, industrial dusts, hepatitis virus, chromium and its compounds,
      lead and its inorganic compounds, carbon disulphide and carbon monoxide pose the
      highest risk. Apart from the statistics concerning the number of cases of
      occupational diseases according to sex, age, exposure duration, national economy
      branches and regions (voivodeships), the article presents, for the first time,
      some consequences of occupational diseases, such as granting disability pensions
      and/or indemnity depending on the per cent of health impairment.

PMID- 8142775
TI  - Creating new opportunities--Nancy Dickenson-Hazard, RN, CPNP, MSN, FAAN.
      Interview by Marcia Stanhope.

PMID- 8142776
TI  - Sigma Theta Tau founder dies. To begin.

PMID- 8142777
TI  - Problems attaining local anesthesia with endodontic emergencies.
AB  - The attainment of profound local anesthesia in the management of pulpal and
      periradicular pain often eludes even the most skilled clinician; various reasons
      for this include, but are not limited to, localized inflammation, osseous and
      neural variations, and poor technique of the operator. This paper reviews these
      potential impediments while focusing on recognizing occurrences, understanding
      mechanisms, and applying clinical techniques to effectively eliminate their
      impact on dental pain management.

PMID- 8142778
TI  - Sudden unconsciousness during local anesthesia.
AB  - This case demonstrates the necessity of adequate emergency management during
      dental treatment. A 57-year-old man loses consciousness immediately after the
      injection of a dental local anesthetic. For medical assistance, a neighboring
      general practitioner is first telephoned without success. After approximately 15
      minutes, an ambulance is telephoned, but the caller gave no indication of the
      situation being life threatening. Finally, an emergency doctor is dispatched and
      arrives approximately 35 minutes after the emergency situation began. The
      electrocardiogram shows a supraventricular tachycardia which, after an immediate
      cardioversion, converts to a sinus rhythm connected with a restoration of the
      circulatory function. This case exemplifies the consequences of an inadequate
      response to a sudden emergency.

PMID- 8142779
TI  - Diffusion hypoxia: another view.
AB  - Arterial oxygen saturation (SaO2) was monitored postoperatively with pulse
      oximetry in 80 dental patients receiving nitrous oxide and oxygen. These patients
      were divided into four equal groups, three of which received nitrous oxide (N2O)
      and oxygen (O2) in ratios of 20:80, 40:60, and 60:40, respectively. The fourth
      group received 100% O2 and served as the control. The SaO2 was monitored for 15
      minutes after termination of the procedure as the patient breathed room air.
      Continuous pulse oximetry revealed 43 episodes of SaO2 (a decrease greater than
      3% from the baseline) in patients who received 20% N2O, 268 episodes in patients
      who received 40% N2O, 594 episodes in patients who received 60% N2O, and 21
      episodes in patients who received 100% O2. The number of patients who experienced
      desaturation episodes increased with the increase in N2O concentration. The SaO2
      values ranged from a decrease of 1.0% to 7.0% with a mean of 2.1%. Smokers
      experienced a greater number of desaturation episodes in the 40% N2O group and in
      the control group. One patient in the 40% N2O group experienced an SaO2 of less
      than 90%, but no patient experienced clinically significant hypoxia. In the 40%
      and 60% N2O groups, the percent change of SaO2 from the baseline was greater, and
      the SaO2 returned to baseline slower. The difference in mean SaO2 between smokers
      and nonsmokers was greater in the 40% N2O group.

PMID- 8142780
TI  - Anxiety measures during induced experimental pain.
AB  - Results of analgesic studies obtained using experimental pain are often not
      comparable with those obtained from clinical studies. This may be because
      anxiety, which plays an important role in the pain experience, may not be evoked
      by experimentally induced pain. The aim of this study is to measure the level of
      anxiety induced by the submaximum effort tourniquet technique, which produces
      pain similar in quality to clinical pain. The mean time that subjects tolerated
      the pain from the tourniquet was 14.94 minutes. Systolic blood pressure and heart
      rate increased. Visual analogue scale measures of anxiety showed an overall
      increase during the experiment but were highly erratic individually. This study
      suggests that the submaximum effort tourniquet technique is incapable of inducing
      the same type of anxiety experienced with clinical pain.

PMID- 8142781
TI  - Oral mucosal analgesia quantitatively assessed by argon laser-induced thresholds
      and single-evoked vertex potentials.
AB  - The aim of this study is to quantitate the efficacy of a new topical anesthetic
      applied to the oral mucosa. Nociceptive pinprick thresholds and single-evoked
      vertex potentials (VP) elicited by high-intensity argon laser stimuli are used as
      measures of analgesia. After 5 minutes of occlusion (Orahesive Oral Bandages,
      ConvaTec) with a eutectic mixture of local anesthetics (EMLA cream, Astra),
      nociceptive pinprick thresholds on the tongue and gingiva are higher than those
      taken during nonocclusion. In a double blind-placebo controlled experiment, VPs
      were elicited every 1 minute for 19 minutes by single laser stimuli applied to
      the mucosa of the lower lip. After occlusion with EMLA cream for 3 minutes, VPs
      were significantly reduced when compared to those with placebo cream. One minute
      after removal of the EMLA cream, the spectral power of the single-evoked VP
      decreased significantly by 63.3%, the root-mean-square amplitude decreased by
      42.7%, and the subjective pain perception (estimated on visual analogue scales)
      decreased by 88%. A significant reduction in single-evoked VPs was detected until
      13 minutes after the removal of the EMLA cream. Oral mucosal analgesia may be
      quantitated by argon laser-induced nociceptive pinprick thresholds and single
      evoked VPs.

PMID- 8142782
TI  - Systemic management of Marfan's syndrome during dental treatment: a case report.
AB  - Marfan's syndrome is a dominantly inherited connective tissue disorder
      characterized by skeletal, ocular, and cardiovascular abnormalities, such as
      arachnodactyly, dolichostenomelia, kyphosis, scoliosis, pectus excavatum, ectopia
      lentis, aortic aneurysm and dissection, aortic valve incompetence, and mitral
      valve prolapse. This report describes the systemic management during dental
      treatment of a 26-year-old man with Marfan's syndrome. Blood pressure,
      electrocardiogram, echocardiography, systolic time intervals, and aortic pulse
      wave velocity were monitored. Nitrous oxide inhalational sedation was employed.
      In contrast to the vasopressin, felypressin (contained in prilocaine),
      epinephrine (contained in lidocaine) caused an acceleration of cardiac function-
      increased heart rate, cardiac output, 1/pre-ejection period (PEP), and aortic
      pulse wave velocity and decreased PEP and left ventricular ejection time. This
      experience suggests that the use of anesthetics containing epinephrine in dental
      patients with Marfan's syndrome needs to be carefully managed.

PMID- 8142783
TI  - The effect of an electronic analgesia device on dental pain thresholds.
AB  - The effect of UltraCalm, an electronic dental analgesia (EDA) device, on dental
      pain thresholds was studied in 32 volunteers. For each subject, two initial
      baseline measurements of dental pain thresholds were made using an electric pulp
      tester. Pain thresholds were then measured during EDA with either UltraCalm or an
      inactive (placebo) device. No significant differences were found between the
      first and second baseline threshold measurements nor between the pain thresholds
      measured during the application of the UltraCalm and placebo devices. The mean
      baseline pain threshold was significantly lower than the threshold measured
      during application of the placebo device, but was not significantly different
      from the threshold during application of UltraCalm. it is concluded that
      UltraCalm has no consistent effect in altering dental pain thresholds.

PMID- 8142784
TI  - A comparison of injectable local anesthesia and electronic dental anesthesia in
      restorative dentistry.
AB  - This study compares patient satisfaction and subjective pain levels with either
      electronic dental anesthesia (EDA) or injectable local anesthesia (LA) during the
      placement of direct restorations. Twenty-five patients (mean age 41 years), who
      each required two similar restorations in vital teeth, were selected. One
      restoration was placed using EDA and the other using LA. Preoperatively, all
      participants completed the Corah Dental Anxiety Scale, and postoperatively they
      completed a satisfaction questionnaire. Fifteen (60%) patients preferred EDA to
      LA, and 7 (28%) had no preference. Asked to rate their feelings on the prospect
      of having a filling placed with either EDA or LA (scale 1 to 5, very anxious to
      very relaxed), the patients rated LA as 3.0 and EDA as 3.6 (mean scores). Some
      pain or discomfort was felt by 12 patients with EDA and 14 patients with LA. On a
      scale of discomfort (1 to 5, very slight to very severe), the mean score was 1.0
      for EDA and 1.2 for LA.

PMID- 8142785
TI  - Improving the poor prognosis of oral squamous cell carcinoma.

PMID- 8142786
TI  - Asymptomatic infection with hepatitis C virus.

PMID- 8142787
TI  - Reactive arthritis.

PMID- 8142788
TI  - Alzheimer's disease.

PMID- 8142789
TI  - Towards the safer use of traditional remedies.

PMID- 8142790
TI  - Control of blood pressure and risk of first acute myocardial infarction:
      Skaraborg hypertension project.
AB  - OBJECTIVE: To analyse the relation between treated blood pressure and concomitant
      risk factor and morbidity from acute myocardial infarction. DESIGN: Prospective
      longitudinal study. Treated blood pressures and other variables were used to
      predict acute myocardial infarction. SETTING: Primary health care in Skaraborg,
      Sweden. SUBJECTS: 1121 men and 1453 women aged 40-69 years at registration at
      outpatient clinics, 1977-81, with no evidence of previous myocardial infarction
      were followed up for an average of 7.4 years. Subjects were undergoing treatment
      with drugs to lower blood pressure or had blood pressure that exceeded the
      systolic or diastolic limits, or both, for diagnosis (> 170/> 105 mm Hg (patients
      aged 40-60 years) and > 180/> 110 mm Hg (older than 60 years)) on three different
      occasions, or both. MAIN OUTCOME MEASURES: First validated event of fatal or non
      fatal acute myocardial infarction. RESULTS: In men but not in women there was a
      negative relation between treated diastolic blood pressure and risk of acute
      myocardial infarction. Left ventricular hypertrophy and smoking were contributory
      risk factors in both sexes, as was serum cholesterol concentration in men. In men
      with normal electrocardiograms (n = 345) risk increased with increasing diastolic
      blood pressure (P = 0.047), whereas the opposite was found in men with
      electrocardiograms suggesting ischaemia or hypertrophy, or both (n = 499, P =
      0.009). In those with a reading of 95-99 mm Hg the relative risk was 0.30 (P =
      0.034); at > or = 100 mm Hg it was 0.37 (P = 0.027). No similar relations were
      seen in women or for systolic blood pressure. CONCLUSION: It may be hazardous to
      lower diastolic blood pressure below 95 mm Hg in hypertensive men with possible
      ischaemia or hypertrophy, or both. Electrocardiographic findings should be
      considered when treatment goals are decided for men with hypertension.

PMID- 8142791
TI  - First step in managing bulimia nervosa: controlled trial of therapeutic manual.
AB  - OBJECTIVE: To test the short term efficacy of a self directed treatment manual
      for bulimia nervosa. DESIGN: Randomised controlled trial of the manual against
      cognitive behavioural therapy and a waiting list. SETTING: Tertiary referral
      centre. SUBJECTS: 81 consecutive referrals presenting with bulimia nervosa or
      atypical bulimia nervosa. MAIN OUTCOME MEASURES: Frequency of binge eating,
      vomiting, and other behaviours to control weight as well as abstinence from these
      behaviours. RESULTS: Cognitive behavioural treatment produced a significant
      reduction in the frequency of binge eating, vomiting, and other behaviours to
      control weight. The manual significantly reduced frequency of binge eating and
      weight control behaviours other than vomiting, and there was no change in the
      group on the waiting list. Full remission was achieved in five (24%) of the group
      assigned to cognitive behavioural treatment, nine (22%) of the group who used the
      manual, and two (11%) of the group on the waiting list. CONCLUSIONS: A self
      directed treatment manual may be a useful first intervention in the treatment of
      bulimia nervosa.

PMID- 8142792
TI  - Suprapubic aspiration under ultrasound guidance in children with fever of
      undiagnosed cause.
AB  - OBJECTIVES: To assess the ease of use of suprapubic aspiration of urine under
      ultrasound guidance in babies with fever of uncertain cause and to assess the
      importance of bacterial counts and pyuria in relation to abnormalities of the
      urinary tract and the importance of pyuria in the absence of bacteriuria. DESIGN:
      Analysis of urine samples obtained by suprapubic aspiration in babies and
      children from July 1991 to June 1992. The clinical records of the children with
      bacteriuria and sterile pyuria were examined retrospectively. SETTING: Neonatal
      and paediatric wards of a district general hospital. SUBJECTS: 508 babies and
      children who had fever of uncertain cause or were seriously ill. RESULTS: No
      difficulties arose in the collection of 545 specimens. Bacteria were isolated
      from the specimens of 44 children, 24 of whom had abnormalities of the urinary
      tract. The bacterial count was < 10(8)/l in 18 of the children with bacteriuria,
      10 of whom had abnormalities. No white cells were seen in 22 of the 46
      bacteriuric specimens; nine of the children with no pyuria had vesicoureteric
      reflux. 439 of the 499 non-bacteriuric specimens showed no white cells. 60
      children had pyuria without bacteriuria. CONCLUSIONS: The use of ultrasound
      guidance simplifies suprapubic aspiration of urine in babies. Low bacterial
      counts may be associated with abnormalities of the urinary tract. Laboratory
      techniques capable of detecting such counts reliably should be used. Pyuria is
      absent in half of babies and very young children with bacteriuria. It rarely
      occurs without bacteriuria, and if it does an explanation should be sought.

PMID- 8142793
TI  - Skin test reactivity and number of siblings.
AB  - OBJECTIVE: To investigate the relation between skin test reactivity in children
      and number of siblings. DESIGN: Cross sectional survey among schoolchildren aged
      9-11 years. Skin prick tests in the children and self completion of written
      questionnaire by their parents. SUBJECTS: 5030 children in Munich and 2623
      children in Leipzig and Halle, Germany. MAIN OUTCOME MEASURES: Atopic status
      assessed by skin prick tests. RESULTS: After possible confounders were controlled
      for, the prevalence of atopic sensitisation decreased linearly with increasing
      number of siblings (odds ratio = 0.96 for one sibling, 0.67 for five or more
      siblings; P = 0.005). In atopic children the severity of the skin test reaction
      as assessed by the weal size was not associated with the number of siblings.
      CONCLUSIONS: Factors directly or indirectly related to the number of siblings may
      decrease the susceptibility of children to become atopic. Thus, declining family
      size may in part contribute to the increased prevalence of atopic diseases
      reported in Western countries over the past few decades.

PMID- 8142794
TI  - Chronic hepatitis in United Kingdom blood donors infected with hepatitis C virus.
      Trent Regional Hepatitis C Virus Study Group.

PMID- 8142795
TI  - Normal aminotransferase concentrations in patients with antibodies to hepatitis C
      virus.

PMID- 8142796
TI  - Listening to local voices: adapting rapid appraisal to assess health and social
      needs in general practice.
AB  - OBJECTIVES: To explore the use of rapid appraisal in defining the health and
      social needs of a community and to formulate joint action plans between the
      residents and service providers. DESIGN: Collection of data by an extended
      primary care team from three sources: existing documents about the neighbourhood,
      interviews with a range of informants, and direct observations to build a profile
      of the community. SETTING: Council estate of 670 homes in Edinburgh. MAIN OUTCOME
      MEASURES: Perceived problems of the community and suggestions for change.
      RESULTS: The interviews and focus groups identified six priorities for change,
      many of which were not health related. These changes have been or are being
      implemented. CONCLUSIONS: An expanded primary care team can use rapid appraisal
      as a first step in identifying and meeting local health needs. It facilitates a
      multidisciplinary approach and complements quantitative methods of assessing
      need.

PMID- 8142797
TI  - Management of community acquired lower respiratory tract infection.

PMID- 8142798
TI  - Is there an epidemic of cancer?
AB  - Trends in cancer mortality in England and Wales are dominated by a slowly
      evolving epidemic of lung cancer attributable to smoking. When the substantial
      effects of tobacco are discounted there is no evidence that the overall incidence
      of cancer is rising, but striking trends are apparent for several specific
      tumours. These may offer important clues to aetiology.

PMID- 8142799
TI  - Community care in Bassetlaw.
AB  - Last April the United Kingdom's system for providing community care--practical
      and social care for ill and disabled people who need help with daily life--was
      changed in an effort to make it better and more efficient. The BMJ ran a series
      of articles about the changes that included descriptions of community care in
      four places: Gwent in Wales, Bassetlaw in Nottinghamshire, Northern Ireland, and
      Newcastle in north east England. In this and the next three articles we look at
      what has happened to community care over the past year in these places.

PMID- 8142800
TI  - The terror of television. Anxious children at greater risk.

PMID- 8142801
TI  - The terror of television. Distress not confined to children.

PMID- 8142802
TI  - The terror of television. Made worse by family stress.

PMID- 8142803
TI  - Management of breast cancer. Refer women to multidisciplinary breast clinics.

PMID- 8142804
TI  - Management of breast cancer. Incomplete case notes hamper research.

PMID- 8142805
TI  - Management of breast cancer. Neurological symptoms may not be due to
      radiotherapy.

PMID- 8142806
TI  - Management of breast cancer. Attack on radiotherapy too simplistic.

PMID- 8142807
TI  - Chlamydia trachomatis infection. Prevalence varies in general practice.

PMID- 8142808
TI  - Management of breast cancer. Self referral service is unique.

PMID- 8142809
TI  - Management of breast cancer. Understand women's preconceptions.

PMID- 8142810
TI  - Depot medroxyprogesterone acetate and osteoporosis. Monitor serum oestradiol
      concentration in users.

PMID- 8142811
TI  - Cystoscopy in bladder cancer.

PMID- 8142812
TI  - Treatment of heroin users.

PMID- 8142813
TI  - Adult epiglottitis. Causative organism may be elusive.

PMID- 8142814
TI  - Adult epiglottitis. Don't waste time with radiography.

PMID- 8142815
TI  - Adult epiglottitis. Heightened awareness saves lives.

PMID- 8142816
TI  - Intrapartum monitoring in rural Africa.

PMID- 8142818
TI  - Women consultants.

PMID- 8142817
TI  - Screening immigrants at risk of tuberculosis.

PMID- 8142819
TI  - Management of preterm labour. Avoid ergometrine in the third stage.

PMID- 8142820
TI  - Management of preterm labour. Safety of hormone treatment unproved.

PMID- 8142821
TI  - Alcohol histories taken from elderly people.

PMID- 8142822
TI  - Towards rational prescribing.

PMID- 8142823
TI  - Chronic fatigue syndrome: prevalence and outcome.

PMID- 8142824
TI  - Who cares for young carers?

PMID- 8142825
TI  - Suspected myocardial infarction and the GP.

PMID- 8142826
TI  - What's happening to practice nursing?

PMID- 8142827
TI  - Case-control study of intrapartum care, cerebral palsy, and perinatal death.
AB  - OBJECTIVE: To investigate the relation between suboptimal intrapartum obstetric
      care and cerebral palsy or death. DESIGN: Case-control study. SETTING: Oxford
      Regional Health Authority. SUBJECTS: 141 babies who subsequently developed
      cerebral palsy and 62 who died intrapartum or neonatally, 1984-7. All subjects
      were born at term of singleton pregnancies and had no congenital anomaly. Two
      controls, matched for place and time of birth, were selected for each index case.
      MAIN OUTCOME MEASURES: Adverse antenatal factors and suboptimal intrapartum care
      (by using predefined criteria). RESULTS: Failure to respond to signs of severe
      fetal distress was more common in cases of cerebral palsy (odds ratio 4.5; 95%
      confidence interval 2.4 to 8.4) and in cases of death (26.1; 6.2 to 109.7) than
      among controls. This association persisted even after adjustment for increased
      incidence of a complicated obstetric history in cases of cerebral palsy. Neonatal
      encephalopathy is regarded as the best clinical indicator of birth asphyxia; only
      two thirds (23/33) of the children with cerebral palsy in whom there had been a
      suboptimal response to fetal distress, however, had evidence of neonatal
      encephalopathy; these 23 formed 6.8% of all children with cerebral palsy born to
      residents of the region in the four years studied. CONCLUSION: There is an
      association between quality of intrapartum care and death. The findings also
      suggest an association between suboptimal care and cerebral palsy, but this seems
      to have a role in only a small proportion of all cases of cerebral palsy. The
      contribution of adverse antenatal factors in the origin of cerebral palsy needs
      further study.

PMID- 8142828
TI  - Relation between infection with Helicobacter pylori and living conditions in
      childhood: evidence for person to person transmission in early life.
AB  - OBJECTIVES: To relate the prevalence of infection with Helicobacter pylori in
      adults to their living conditions in childhood to identify risk factors for
      infection. DESIGN: Prevalence study of IgG antibodies to H pylori (> 10
      micrograms IgG/ml, determined by enzyme linked immunosorbent assay (ELISA)) and
      reported living conditions and other socioeconomic factors in childhood. SETTING:
      Three factories in Stoke on Trent. SUBJECTS: 471 male volunteers aged 18 to 65
      years. MAIN OUTCOME MEASURES: Seroprevalence and variables in childhood. RESULTS:
      Seroprevalence of H pylori increased with age (22/74 (29.7%) at < 30 years v
      29/46 (63%) at 55-65 years; P < 0.001 for trend) and was related to manual
      occupation (14/65 (21.5%) for non-manual v 162/406 (39.9%) for manual; P =
      0.003). After data were adjusted for age and occupation subjects from large
      families, whose childhood homes were crowded or who regularly shared a bed in
      childhood, were significantly more likely to be seropositive (adjusted odds ratio
      (95% confidence interval) 2.15 (1.41 to 3.30) for crowding and 2.13 (1.38 to
      3.30) for sharing a bed), but there was no relation with possession of a
      bathroom, inside toilet, refrigerator, or household pets in childhood.
      CONCLUSIONS: Close person to person contact in childhood is an important
      determinant of seroprevalence of H pylori in adulthood, suggesting that the
      infection is transmitted directly from one person to another and may be commonly
      acquired in early life.

PMID- 8142829
TI  - Taping the patella medially: a new treatment for osteoarthritis of the knee
      joint?
AB  - OBJECTIVE: To test the hypothesis that medial taping of the patella reduces the
      symptoms of osteoarthritis of the knee when the patellofemoral joint is affected.
      DESIGN: Randomised, single blind, crossover trial of three different forms of
      taping of the knee joint. Each tape (medial, lateral, or neutral) was applied for
      four days, with three days of no treatment between tape positions. SUBJECTS: 14
      patients with established, symptomatic osteoarthritis of the knee and both
      clinical and radiographic evidence of patellofemoral compartment disease. MAIN
      OUTCOME MEASURES: Daily visual analogue scale ratings for pain; patients' rating
      of change with each treatment; and tape preference. RESULTS: Medial taping of the
      patella was significantly better than the neutral or lateral taping for pain
      scores, symptom change, and patient preference. The medial tape resulted in a 25%
      reduction in knee pain. CONCLUSION: Patella taping is a simple, safe, cheap way
      of providing short term pain relief in patients with osteoarthritis of the
      patellofemoral joint.

PMID- 8142830
TI  - Longitudinal study of outcome of chronic fatigue syndrome.
AB  - OBJECTIVE: To examine the predictors of long term outcome for patients with the
      chronic fatigue syndrome. DESIGN: Cohort study. SUBJECTS: 139 subjects previously
      enrolled in two treatment trials; 103 (74%) were reassessed a mean of 3.2 years
      after start of the trials. SETTING: University hospital referral centre. MAIN
      OUTCOME MEASURES: Age at onset, duration of illness, psychological and
      immunological status at initial assessment. Ongoing symptom severity, levels of
      disability, and immunological function at follow up. RESULTS: 65 subjects had
      improved but only six reported no current symptoms. An alternative medical
      diagnosis had been made in two and psychiatric illness diagnosed in 20. The
      assignment of a primary psychiatric diagnosis at follow up and the strength of
      the belief that a physical disease process explained all symptoms at entry to the
      trials both predicted poor outcome. Age at onset of illness, duration of illness,
      neuroticism, premorbid psychiatric diagnoses, and cell mediated immune function
      did not predict outcome. CONCLUSION: Though most patients with the chronic
      fatigue syndrome improve, a substantial proportion remain functionally impaired.
      Psychological factors such as illness attitudes and coping style seem more
      important predictors of long term outcome than immunological or demographic
      variables.

PMID- 8142831
TI  - Use of aspirin by general practitioners in suspected acute myocardial infarction.

PMID- 8142832
TI  - Survey of whether general practitioners carry aspirin in their doctor's bag.

PMID- 8142833
TI  - Survey of elderly people who get stuck in the bath.

PMID- 8142834
TI  - Guidelines for the early management of patients with myocardial infarction.
      British Heart Foundation Working Group.
AB  - In light of recent publications relating to resuscitation and pre-hospital
      treatment of patients suffering acute myocardial infarction of British Heart
      Foundation convened a working group to prepare guidelines outlining the
      responsibilities of general practitioners, ambulance services, and admitting
      hospitals. The guidelines emphasise the importance of the rapid provision of
      basic and advanced life support; adequate analgesia; accurate diagnosis; and,
      when indicted, thrombolytic treatment. The working group developed a standard
      whereby patients with acute myocardial infarction should receive thrombolysis,
      when appropriate, within 90 minutes of alerting the medical or ambulance service-
      the call to needle time. Depending on local circumstances, achieving this
      standard may involve direct admissions to coronary care units, "fast track"
      assessments in emergency departments, or pre-hospital thrombolytic treatment
      started by properly equipped and trained general practitioners.

PMID- 8142835
TI  - Can there be fair funding for fundholding practices?
AB  - Most regional health authorities set budgets for fundholding practices according
      to the amount of care used by the practice population. This article explains why
      this funding method can only lead to an inequitable allocation of resources
      between fundholding and non-fundholding practices. Using the experience of North
      West Thames region, the efforts made to make funding fairer are discussed. The
      steps that health authorities could take to investigate and reduce the problem
      are also outlined. In the absence of a capitation formula for funding fundholding
      practices, the paper suggests that health authorities should do much more to
      investigate the amount of money they spend on non-fundholding practices. Regions
      could develop and use other methods to set budgets rather than rely on activity
      recorded by practices. Regions and the Department of Health should resolve
      urgently if and how far the budgets for fundholders should be compensated for
      increases in provider prices.

PMID- 8142836
TI  - Professional and popular views of chronic fatigue syndrome.
AB  - OBJECTIVE: To study the coverage of the chronic fatigue syndrome in the popular
      and professional press. DESIGN: Search of all original research papers on the
      chronic fatigue syndrome published in British journals from 1980 onwards and of
      professional trade papers, national newspapers, and women's magazines. Interviews
      with six medical journalists. SETTING: British scientific, medical, and popular
      press. RESULTS: 37 (49%) articles in research journals did not favour organic
      causes and 23 (31%) favoured organic causes. By contrast 31 (55%) articles in the
      medical trade press and 118 (69%) in national newspapers and women's magazines
      favoured organic causes. CONCLUSIONS: Press coverage of chronic fatigue syndrome
      has amplified and distorted divisions in the research community concerning the
      chronic fatigue syndrome. Articles in the press concentrate on a simple medical
      model of illness reinforcing the stigma of psychological illness and
      dissatisfaction with traditional medical authority.

PMID- 8142837
TI  - Community care: the first year. Gwent: a good start and better prospects.

PMID- 8142839
TI  - Bacterial vaginosis and preterm delivery. Little evidence of causal association.

PMID- 8142838
TI  - Cancer of the prostate.
AB  - Prostate cancer presents a growing health problem in Western societies as
      longevity increases. It is characteristically a disease of elderly men associated
      with the development of osteoblastic bone metastases and initial hormone
      responsiveness to androgen deprivation. Previously regarded as a Cinderella of
      cancers, there is currently more controversy concerning the detection and
      management of both localised and metastatic disease than for any other common
      malignancy. A balance needs to be drawn between the potential gains of more
      aggressive management and the disadvantages in terms of increased treatment side
      effects and cost, taking into account both the natural course of the disease and
      the life expectancy of patients.

PMID- 8142840
TI  - Bacterial vaginosis and preterm delivery. Spurious link may lead to
      overtreatment.

PMID- 8142841
TI  - Haematuria clinics. Open access is useful if rapid treatment is available.

PMID- 8142842
TI  - Human gonadotrophin preparations. Patients can't afford new drug.

PMID- 8142843
TI  - HIV infection in Uganda.

PMID- 8142844
TI  - Increasing rate of deliberate self poisoning.

PMID- 8142845
TI  - Women's reproductive health. Women left destitute by AIDS.

PMID- 8142846
TI  - Women's reproductive health. Pregnancy causing a "silent slaughter" in the
      developing world.

PMID- 8142847
TI  - Collecting data on cancer.

PMID- 8142848
TI  - Metal implants and cremation.

PMID- 8142849
TI  - Screening for breast cancer.

PMID- 8142850
TI  - Invasive meningococcal infection after splenectomy.

PMID- 8142851
TI  - Health care in US and Canada.

PMID- 8142852
TI  - Training in paediatric life support.

PMID- 8142853
TI  - [Experimental epidural and conduction anesthesia with azacaine].
AB  - Experimental studies were undertaken to examine azacaine used in mice during
      conduction anesthesia and in rabbits during epidural anesthesia in 0.75, 2 and
      0.75, 1% solutions, respectively. It was found that azacaine in the above doses
      is 1.5-3.5-fold superior to 2% solutions of lidocaine (xycaine) and trimecaine
      (mesocaine) in their effect duration. Histological studies of the rabbit spinal
      cord after epidural azacaine administration revealed no significant changes in
      brain tissues.

PMID- 8142854
TI  - [The dependence of the effects of naloxone on the type of nociceptive stimulus].
AB  - The dynamics of latent periods of the tail-flick reaction in response to thermal
      nociceptive stimulus (TNS) and electrocutaneous nociceptive stimulus (ENS) was
      studied in Wistar rats. Naloxone, 1.4 and 2.8 mg/kg, intraperitoneally injected
      evoked analgesia in response to TNS and hyperalgesia in response to ENS. It is
      suggested that the bidirectional effects of naloxone are associated with the
      specificity of nociceptive mechanisms activated by different pain stimuli.

PMID- 8142855
TI  - [Calcium channel blockers as antidepressants--a property of the class or of the
      individual preparation?].
AB  - Only did nifedipine and fendiline decrease immobilization time in mice in the
      tail suspension test. 5-Hydroxytryptophan-induced head-twitches were slightly
      (insignificantly) diminished by nifedipine and verapamil. The two drugs
      potentiated the hypothermic action of reserpine. Fendiline and cinnarizine
      increased the effect of 5-hydroxytryptophan, but did not modify the effect of
      reserpine. Diltiazem was virtually inactive in these tests. All the calcium
      channel blockers decreased the cataleptic action of haloperidol. It is concluded
      that nifedipine and fendiline are promising in stress-induced reactive
      depression.

PMID- 8142856
TI  - [The central vascular and metabolic effects of pyroglutamic acid].
AB  - The ability of pyroglutamic acid, a cyclic glutamic acid derivative, to increase
      cerebral blood flow, to decrease the resistance of brain vessels, and to relax
      the isolated grafts of cerebral arteries has been demonstrated. Pyroglutamic acid
      markedly stimulated brain metabolism: increased glucose uptake and utilization by
      cerebral tissues and decreased brain lactate dehydrogenase activity.

PMID- 8142858
TI  - [The effect of perindoprilat on the cardiovascular system of rats with heart
      failure].
AB  - The effect of intravenous perindoprilat, 0.5 mg/kg, on regional blood flow
      (radioactive microspheres, 15 microns), systemic hemodynamics, vein tone and
      cardiac functions was evaluated in conscious rats with congestive heart failure.
      Experimental heart failure was induced by embolization of coronary vessels with
      microspheres 21 days before the experiment. Perindoprilat reduced mean arterial
      pressure, total peripheral resistance, and end-diastolic left ventricular
      pressure. Perindoprilat induced an increase in cardiac index, stroke volume and
      heart rate. Blood flow in the renal, small intestinal and skin vascular beds was
      more profound in the heart failure group than in sham-operated animals.
      Perindoprilat unchanged the mean circulatory filling pressure in sham-operated
      animals and decreased it by 15% in rats with heart failure.

PMID- 8142857
TI  - [The effect of ethomersol on local cerebral blood flow and edema of the brain
      tissue in chronic ischemia].
AB  - The effects of ethomersole (50 mg/kg orally during 10 days) on local cerebral
      blood flow and cerebral tissue impedance were investigated in rats after left
      carotid artery ligation and right carotid artery narrowing (blood flow was
      decreased to 50%). Under these conditions, ethomersole accelerated the blood flow
      recovery, levelled blood flow asymmetry between the hemispheres, decreased the
      development of brain edema. In in vitro experiments ethomersole demonstrated a
      pronounced limitation of cerebral lipid peroxidation.

PMID- 8142859
TI  - [The antiarrhythmic activity of glycolysis and Krebs cycle intermediates in early
      occlusion and reperfusion arrhythmias in rats].
AB  - Acute experiments on unconscious rats have demonstrated that fructose-1,6
      diphosphate, phosphoenolpyruvate and malate of sodium produced a marked
      antiarrhythmic activity in acute occlusive and reperfusion arrhythmias, prevented
      the development of ventricular fibrillation and tachycardias, considerably
      reduced the duration of arrhythmia paroxysms, but they were ineffective in
      ventricular extrasystole.

PMID- 8142860
TI  - [The pharmacokinetic interaction of propranolol and nifedipine in patients with
      angina of effort].
AB  - A comprehensive study was undertaken to examine the pharmacokinetic and
      pharmacodynamic interaction of propranolol and nifedipine in 11 patients with
      stable angina of effort who were treated for a long time. It was shown that when
      the agents were given in combination, the patient's plasma generated the same
      profiles of their concentrations as used alone. This suggests that the
      propranolol + nifedipine combination is safe from the point of their
      pharmacokinetic interaction. The latter occurs at the level of their
      pharmacodynamic effects.

PMID- 8142862
TI  - [The mechanisms of the hepatotoxicity of complex platinum compounds].
AB  - Cisplatin and platin given in LD50 to mice caused significant changes in hepatic
      metabolism. There was enhanced lipid peroxidation with accumulation of malonic
      dialdehyde, dienic conjugates, Schiff bases, decreased antiradical activity and
      alterations in the fractional composition of phospholipids with higher
      concentrations of membranotoxic ingredients. There was also an increase in the
      serum activity of transaminases and alkaline phosphatase.

PMID- 8142861
TI  - [The effect of chenophalk on the liver function of intact animals and in
      experimental hepatitis].
AB  - Chenophalk (chenodeoxycholeic acid) was given to Wistar rats, including intact
      animals and those with chronic toxic hepatitis, in daily oral dose of 15 mg/kg
      body weight during 11 days. Chronic toxic hepatitis was induced by 7 subcutaneous
      injections of carbon tetrachloride (0.3 ml of 50% oil solution per kg body
      weight) each three days. Chenophalk was shown to impair bile crystallization. It
      enhanced demethylase activity, elevated the levels of cytochromes P-450 and b5 in
      the liver microsomal fraction, and decreased lipid peroxidation just after
      injection. The agent normalized oxygen tension in the liver tissue, which had
      been reduced by carbon tetrachloride. Chenophalk caused disturbances in the
      structure of the liver and in microcirculation early after injection, showing a
      tendency to normalize the histostructure of the liver.

PMID- 8142863
TI  - [Polypharmacotherapy: the risk of developing postoperative hemorrhages].
AB  - The impact of polypragmasy on the causes of endogenic heparinemia in the early
      postoperative period was studied in patients operated on the heart under
      extracorporeal circulation. It has been found that polypragmasy does not break
      down the heparin-protamine sulfate complex, but impairs the process of its
      formation to a certain degree. Ascorbic acid lowers the activity of heparin and
      hence it may be used as a hemostatic stabilizer during endogenous heparinemia.

PMID- 8142864
TI  - [The mechanism of the damaging action of hypoxia on the respiratory chain and the
      means for its pharmacological correction].

PMID- 8142865
TI  - [The specificity of the antioxidant protection systems of the organs and tissues-
      a basis for differentiated pharmacotherapy with antioxidants].

PMID- 8142866
TI  - [The characteristics of the pharmacological action of buspirone].
AB  - Some aspects of the anxiolytic action of buspirone were investigated by
      differentiating fear from anxiety. Buspirone showing anxiolytic and antineurotic
      action in the models of anxiety and conflicting situation was demonstrated to be
      inactive in the model of fear of falling down from the elevated cross-shaped
      labyrinth. The antiamnestic effect of buspirone was revealed in the electroshock
      amnesia model. It is assumed that serotonin receptors are possibly responsible
      both for the anxiety and for memory processes.

PMID- 8142867
TI  - [The effect of endogenous opioid peptides and their synthetic analogs on the
      activity of natural killer cells].
AB  - Met- and leu-enkephalins and their synthetic analogs DAGO, DADLE, and dalargin
      were tested for their effects on the activity of natural killer cells. The
      endogenous opioid peptides and dalargin were shown to be able to enhance the
      cytolytic activity of natural killer cells.

PMID- 8142868
TI  - [The effect of endogenous opioid peptides and their synthetic analogs on T-cell
      immunity].
AB  - The effects of the endogenous opioid peptides met- and leu-enkephalins and their
      synthetic analogs such as DAGO, DADLE, dalargin on the formation and activity of
      cytolytic T lymphocytes in response to alloantigen stimulation were studied in
      the unidirectional mixed culture of lymphocytes. It was shown that the maximum
      stimulating effect of the opioids manifested itself on their addition 24-48 hours
      after the initiation of incubation and on addition of suboptimal concentrations
      of an antigen to the culture. The selective opioid receptor ligands mu- and delta
      types + (DAGO and DADLE) have a heterodirectional effect on the formation of
      specific T killer cells in the mixed culture of lymphocytes.

PMID- 8142869
TI  - [Cyclic adenosine monophosphate metabolism in the peripheral blood lymphocytes of
      atopic patients exposed to histamine].
AB  - Radioisotopic assay has shown that in vitro histamine increases the metabolism of
      cyclic adenosine monophosphate (cAMP) through H-2 receptors in the peripheral
      blood lymphocytes of healthy individuals and patients with atopic bronchial
      asthma. In patients who have asphyxia the histamine-induced stimulation of the
      activity of cAMP phosphodiesterase metabolizing cAMP is considerably decreased.
      In is suggested that high cAMP metabolism may be a cause of desensitization of
      histaminic and adrenergic receptors in atopy whose aggravation is accompanied by
      histaminemia.

PMID- 8142870
TI  - [The dopaminergic mechanisms of the action of buspirone and its structural
      analogs].

PMID- 8142871
TI  - [The mechanism of the ulcerogenic action of nonsteroidal anti-inflammatory
      preparations].

PMID- 8142872
TI  - [Enkephalinase inhibitors--a new group of potential analgesics].

PMID- 8142873
TI  - [Prenatal exposure to sodium oxybutyrate prevents a disorder of general behavior,
      learning and memory in the progeny of rats subjected to chronic hemic hypoxia].
AB  - The hemic hypoxia caused by the methemoglobin-inducing agent sodium nitrite (40
      mg/kg intraperitoneally at days 10 to 19 of pregnancy) evokes a decrease in the
      birth and survival rates of pups, delayed disorders of motor coordination.
      Prenatal hypoxia was demonstrated to be able to disturb the habituation in the
      open field, learning and memory in passive avoidance paradigm, cognitive ability
      in the plus-maze extrapolative water escape test. The treatment of pregnant rats
      with sodium hydroxybutyrate (150 mg/kg orally 1-3 times daily at days 12 to 19 of
      pregnancy) normalizes offsprings' birth and survival rates, prevents the above
      mentioned neuropsychological disturbances and improves learning in the active
      avoidance test.

PMID- 8142874
TI  - Study of the retinal fiber layer in patients with acquired immunodeficiency
      syndrome.
AB  - A study using the monochromatic photography technique to examine the retina of a
      group of patients with human immunodeficiency virus (HIV) infections in different
      degrees of evolution and with no history of opportunistic retinal infection
      revealed the existence of lesions on the level of the retinal nerve fiber layer.
      The lesions detected included wide, slit-like defects; sector defects; and
      generalized diffuse atrophies. Both the sector defects and the diffuse atrophies
      appeared at times to be related to retinal cotton-wool exudates, but at other
      times they occurred in eyes with no observable retinal pathology. The results of
      this study can be interpreted as "in vivo" confirmations of the findings obtained
      by other authors in the postmortem study of optic nerves of patients with
      acquired immunodeficiency syndrome (AIDS), presenting a generalized degenerative
      process of the optic nerve with a loss of up to 40% of the axons of the retinal
      ganglion cells. In some cases, the results obtained in our study directly related
      the presence of cotton-wool exudates to the production of lesions in the retinal
      nerve fiber layer, whereas in other cases, the fiber lesions did not appear to be
      secondary to the cotton-wool exudates. Therefore, a primary lesion of the retinal
      ganglion cells or of the optic nerve fibers could be considered, as studies by
      other authors have suggested.

PMID- 8142875
TI  - Anterior proliferative vitreoretinopathy in trauma and complicated retinal
      detachment. A histopathologic study.
AB  - Anterior vitreoretinal proliferations are frequent sequelae of retinal detachment
      repair and severe trauma. Cellular proliferations can form membranes extending
      anteriorly from the peripheral retina. These membranes have the capability to
      contract and may lead to detachment of both the peripheral retina and, in more
      advanced stages, the ciliary body. Because the vitreous base and vitreous
      remnants are leading structures for cellular proliferation, complete removal of
      the anterior vitreous base in particular is important in cases of severe trauma
      or complicated retinal detachment. In 11 cases of anterior proliferative
      vitreoretinopathy examined histopathologically, we found overlying membranes and
      cellular infiltration of the vitreous in close correlation with the amounts of
      vitreous remnants present. Visualization of the peripheral retina and pars plana
      can rarely be accomplished in the presence of the crystalline lens or
      pseudophakia. Therefore, the removal of the anterior vitreous is often
      incomplete. To achieve complete dissection of the anterior vitreous, we remove
      even a clear lens during the first surgical intervention in selected cases.

PMID- 8142876
TI  - Evaluation of eyes harbouring perfluorocarbon liquid with standardized ophthalmic
      echography.
AB  - For the detection of perfluorocarbon liquid (PFCL) left in the globe after
      vitreoretinal surgery, the method of standardized ophthalmic echography proved to
      be very helpful and effective. Larger amounts as well as only a few remnant drops
      of PFCL are represented in standardized A-scans and in contact B-scans by typical
      acoustic signals caused mainly by the slow velocity of ultrasound in PFCL. A safe
      differentiation from other intraocular conditions can be made with standardized
      echography.

PMID- 8142877
TI  - Possible effects of radiobiological parameters on metastatic spread of uveal
      melanomas treated with 106Ru plaques.
AB  - We reviewed 184 cases of uveal melanoma treated with 106Ru eye plaques. The
      influences of the dose rate, the total dose and the initial tumour size on the
      incidence of metastases were of major interest in this retrospective analysis. It
      is widely accepted that the risk of metastatic spread increases with increasing
      tumour volume. However, for tumours measuring < 10 mm in basal diameter the dose
      rate in brachytherapy with 106Ru eye plaques might be important, since we
      observed a better prognosis for patients treated with plaques of relatively low
      activity.

PMID- 8142878
TI  - The photoreceptor cells and retinal pigment epithelium of normal and diseased
      human retinas express different glycoconjugates.
AB  - The photoreceptor cells and retinal pigment epithelium (RPE) represent a highly
      differentiated functional unit that may be disrupted in a variety of retinal
      diseases. We studied the localization and distribution of carbohydrate residues
      in normal and pathologically altered human retinas using lectin histochemical
      techniques. Paraffin-embedded tissue sections were investigated for binding sites
      with six lectins: concanavalin A (Con A), wheat germ agglutinin (WGA), Ricinus
      communis agglutinin (RCA I), peanut agglutinin (PNA), soybean agglutinin (SBA),
      and Ulex europaeus agglutinin (UEA I). Lectin binding to both the photoreceptor
      segments and the RPE was observed in the normal retina with Con A, WGA, RCA I,
      and PNA, particularly to the distal outer segments and to the apical portion of
      RPE cells. Disturbance of the photoreceptor-RPE cell complex occurred in eyes
      with damaged outer retinal layers and those with retinal detachment.
      Photoreceptor cells with a varying degree of inner and outer segment degeneration
      revealed an overall decrease in lectin-binding sites as well as alterations in
      their cellular topography. Reactive and proliferating RPE, however, showed a
      markedly increased reaction intensity for Con A, WGA, RCA I, and PNA as well as
      additional binding sites for SBA in macrophage-like variants. The data are taken
      as evidence that in the normal retina, a characteristic location and distribution
      of lectin-binding sites as well as correspondences in certain cellular
      glycoproteins of both photoreceptor cells and the RPE are indicative of
      structural and functional integrity. Disturbance of the photoreceptor-RPE cell
      complex is accompanied by changes in the expression of lectin-binding sites on
      both cell types.

PMID- 8142879
TI  - Angiotensin II-like immunoreactivity in the retina of some mammalian species.
AB  - The decapeptide angiotensin II (AngII) is a circulating hormone and the most
      important endogenous vasoconstrictor. In the central nervous system (CNS), AngII
      has been reported to have a transmitter-like function. In the retina angiotensin
      I (AngI), the precursor protein of AngII, and AngI-converting enzyme (ACE), the
      rate-limiting enzyme for AngII synthesis, are present. Both ACE inhibition and
      application of an AngII antagonist affect the b-wave of the electroretinogram. In
      the present study we used immunocytochemical techniques to identify putative
      AngII-containing cells in the bovine, cat, and rabbit retina. In the rabbit
      retina, faintly labeled amacrine cells were visible at the inner border of the
      inner nuclear layer. Preincubation with protease inhibitors (PI) resulted in an
      enhanced immunoreaction and in the labeling of ganglion cells and fibers in the
      inner plexiform layer. In the bovine retina, AngII-like immunoreactivity was
      detectable only after preincubation with PI. Under these conditions, ganglion
      cells and amacrine cells as well as cells in more distal parts of the inner
      nuclear layer were stained. In the cat retina, AngII-like immunoreactivity was
      detectable only after preincubation with PI and exogenous AngII. Photoreceptor
      and ganglion cells showed an enhanced AngII-like immunoreaction, and amacrine
      cells were stained preferably in clusters that were irregularly distributed
      within the retina. Our results demonstrate that AngII is a putative
      neurotransmitter in a subpopulation of mammalian amacrine cells.

PMID- 8142880
TI  - Fluctuations of visual field interpretation related to cluster and scotoma
      analysis by one interpreter.
AB  - A total of 189 numerical printouts of the visual fields of 189 eyes of
      individuals either suspected of or verified as having glaucoma and displaying
      varying degrees of glaucomatous visual field damage were analyzed by one expert
      interpreter. The amount of clusters (or scotomas) was counted and delineated in
      each visual field under both a more stringent and a more liberal criterion. The
      interpretations of the visual fields differed significantly in both groups, as
      did the subjective certainty the interpreter allotted to his assessment. In the
      group of certain decisions, only 144 defects were assessed as opposed to 364 when
      a more stringent rather than a more liberal criterion was adopted. In uncertain
      cases, a reverse trend was observed, since only 11 as opposed to 324 defects were
      assessed when a more liberal rather than a more stringent criterion was adopted.
      Both trends may be explained by an increase in sensitivity at the expense of
      specificity (i.e., a change in the receiver-operating characteristic of the
      expert when the latter is pressed to change the criterion in a subjective cluster
      or scotoma assessment task). The ambiguity of the task and the difference in the
      criterion adopted by the interpreter significantly influences the assessment of
      normality and pathology, in particular its extent and spatial distribution.

PMID- 8142881
TI  - Simultaneous measurement of ocular micro- and macrocirculation, intraocular
      pressure, and systemic functions.
AB  - SIMOMIMA (simultaneous measurement of ocular micro- and macrocirculation) is a 32
      channel system for display and analysis of biophysical data on ocular perfusion.
      Using SIMOMIMA in the real-time mode, several parameters of ocular perfusion and
      systemic functions were simultaneously measured noninvasively and stored during
      varying periods of measurement; including ocular macroperfusion (pulsed Doppler
      sonography: ophthalmic artery), ocular microperfusion (laser Doppler flowmetry;
      iris, ciliary body, choroid), intraocular pressure, cardiac pulse, respiration,
      and arterial blood pressure. All data were digitalized and stored by a
      microcomputer for further data processing. With SIMOMIMA in the off-line mode,
      several parameters of the ocular and systemic circulation may be examined and
      correlations between them may be calculated, including absolute values for the
      ophthalmic-artery blood velocity expressed in centimeters per second; the pulse
      wave velocity expressed in centimeters per second; relative values for the
      microcirculatory blood flow of the iris, ciliary body, or choroid; and absolute
      values for and the time course of the intraocular pressure, heart rate, and
      respiration rate. In contrast to the ophthalmic-artery pulse curve, the
      microcirculatory blood flow in the iris showed no obvious synchronization with
      the ECG or the respiration rate. The blood-cell velocity and the blood content in
      the iridal meshwork fluctuated with frequencies ranging between 0.5 and 4 Hz. By
      a special statistical procedure called averaging laser Doppler flowmetry (ALDF),
      the influence of the pulsations of the arterial blood pressure (diastolic
      systolic blood pressure) on the iridial blood flow becomes visible.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8142882
TI  - In vitro anti-human cytomegalovirus activity of liposome-encapsulated foscarnet.
AB  - Foscarnet is a pyrophosphate analogue that possesses substantial activity against
      human cytomegalovirus (HCMV) in patients with CMV retinitis. In this in vitro
      study we tested whether liposome encapsulation of foscarnet would provide the
      drug with anti-HCMV activity comparable with that of nonencapsulated foscarnet.
      The drug was entrapped in large unilamellar vesicles of homogeneous size at a
      concentration of 10 mg/ml. The vesicles were prepared by the method of fast and
      controlled dialysis of mixed detergent-lipid micelles using N-Octyl--D
      glucopyranoside as the detergent. The activity of drugs against two laboratory
      HCMV strains (AD169 and Towne) was tested in a plaque-reduction assay using
      monolayers of human foreskin fibroblasts. The dose of encapsulated or
      nonencapsulated foscarnet required for a 50% reduction in the number of plaques
      (IC50) for the AD169 strain was 106 and 113 mumol/l, respectively. For the HCMV
      Towne strain the dose was 112 and 109 mumol/l, respectively. Treatment with
      concentrations of up to 400 mumol/l (maximal concentration tested) demonstrated
      that foscarnet is released at efficient doses from liposomes and that it is not
      toxic in the range of concentrations tested.

PMID- 8142883
TI  - kappa-Immunoglobulin corneal deposits associated with monoclonal gammopathy.
      Immunohistochemical and electron microscopic findings.
AB  - A 62-year-old man had a 1-year history of bilaterally decreased visual acuity
      associated with irregular, patchy, grayish-white stromal infiltrates involving
      both corneas. As visualized by light microscopy, the keratectomy specimen showed
      numerous homogeneous, eosinophilic deposits located mostly within keratocytes in
      the posterior one-third of the stroma. The deposits stained reddish-brown with
      Masson's trichrome but were periodic acid/Schiff-negative. As visualized by
      electron microscopy, the intracytoplasmic deposits were located within dilated
      cisternae of rough-surfaced endoplasmic reticulum of keratocytes and disclosed a
      10-nm periodicity with a distinct lattice pattern. Immunoperoxidase strains
      confirmed that the deposits contained immunoglobulin (IgG-kappa). At 2 weeks
      following a histopathologic examination of the keratectomy specimen, serum
      protein analysis and immunoelectrophoresis with quantitation of immunoglobulins
      demonstrated an IgG-kappa monoclonal gammopathy. The abnormal corneal deposits
      may be the first clinical sign of a malignant lymphoproliferative process that
      may be associated with a monoclonal gammopathy.

PMID- 8142884
TI  - Analysis of crystalline lens coloration using a black and white charge-coupled
      device camera.
AB  - To analyze lens coloration in vivo, we used a new type of Scheimpflug camera that
      is a black and white type of charge-coupled device (CCD) camera. A new
      methodology was proposed. Scheimpflug images of the lens were taken three times
      through red (R), green (G), and blue (B) filters, respectively. Three images
      corresponding with the R, G, and B channels were combined into one image on the
      cathode-ray tube (CRT) display. The spectral transmittance of the tricolor
      filters and the spectral sensitivity of the CCD camera were used to correct the
      scattering-light intensity of each image. Coloration of the lens was expressed on
      a CIE standard chromaticity diagram. The lens coloration of seven eyes analyzed
      by this method showed values almost the same as those obtained by the previous
      method using color film.

PMID- 8142885
TI  - Retinal detachment in patients with acquired immunodeficiency syndrome.
AB  - Cytomegalovirus retinopathy is the most frequent opportunistic infection of the
      eye in patients with acquired immunodeficiency syndrome (AIDS). We studied 71
      patients with cytomegalovirus retinopathy (n = 69) or acute retinal necrosis (n =
      2) with respect to the frequency and management of retinal detachment. Retinal
      detachment was seen in 14 patients (relative frequency, 19.7%). In 2 patients,
      the retinal detachment was bilateral. In 5 patients, pars plana vitrectomy and
      silicone-oil tamponade was performed, and in 1 of these patients scleral buckling
      was applied before vitrectomy. In 3 other patients scleral buckling was
      performed, and 1 of these individuals had sulfur-hexafluoride injection. In 8
      eyes (6 patients), retinal detachment occurred in eyes with completely burned-out
      retinopathy without relevant function, and no surgical treatment was performed.
      Long-term retinal reattachment was seen in all 5 patients undergoing pars plana
      vitrectomy with silicone-oil tamponade. Visual acuity was preserved until the
      last follow-up in 4 of these 5 patients. In the patients undergoing a buckling
      procedure alone, no anatomic or functional success was observed. During
      vitrectomy, reduced retinal vascular perfusion and blood-flow sludging was
      observed in 2 patients. As the duration of survival of patients with AIDS and
      cytomegalovirus retinopathy or acute retinal necrosis is increasing, more cases
      of retinal detachment will be observed. Overall, 5% of patients with AIDS are
      expected to develop retinal detachment. In conclusion, treatment of
      cytomegalovirus-associated retinal detachment by pars plana vitrectomy with
      silicone-oil tamponade seems to be successful and safe and may maintain the
      patient's quality of life.

PMID- 8142886
TI  - Kinetics and thermodynamics of thermal denaturation in acyl carrier protein.
AB  - The denaturation of Escherichia coli acyl carrier protein (ACP) in buffers
      containing both monovalent and divalent cations was followed by variable
      temperature NMR and differential scanning calorimetry. Both high concentrations
      of monovalent salts (Na+) and moderate concentrations of divalent salts (Ca2+)
      raise the denaturation temperature, but calorimetry indicates that a significant
      increase in the enthalpy of denaturation is obtained only with the addition of a
      divalent salt. NMR experiments in both low ionic strength monovalent buffers and
      low ionic strength monovalent buffers containing calcium ions show exchange
      between native and denatured forms to be slow on the NMR time scale. However, in
      high ionic strength monovalent buffers, where the temperature of denaturation is
      elevated as it is in the presence of Ca2+, the transition is fast on the NMR time
      scale. These results suggest that monovalent and divalent cations may act to
      stabilize ACP in different ways. Monovalent ions may nonspecifically balance the
      intrinsic negative charge of this protein in a way that is similar for native,
      denatured, and intermediate forms. Divalent cations provide stability by binding
      to specific sites present only in the native state.

PMID- 8142887
TI  - On the rate of proton exchange with solvent of the catalytic histidine in
      flavocytochrome b2 (yeast L-lactate dehydrogenase).
AB  - The family of FMN-dependent, alpha-hydroxy acid-oxidizing enzymes catalyzes
      substrate dehydrogenation by a mechanism the first step of which is abstraction
      of the substrate alpha-proton (so-called carbanion mechanism). For
      flavocytochrome b2 and lactate oxidase, it was shown that once on the enzyme this
      proton is lost only slowly to the solvent (Lederer F, 1984, In: Bray RC, Engel
      PC, Mayhew SG, eds, Flavins & flavoproteins, Berlin: Walter de Gruyter & Co., pp
      513-526; Urban P, Lederer F, 1985, J Biol Chem 260:11115-11122). This suggested
      the occurrence of a pKa increase of the catalytic histidine upon enzyme reduction
      by substrate. For flavocytochrome b2, the crystal structure indicated 2 possible
      origins for the stabilization of the imidazolium form of His 373: either a
      network of hydrogen bonds involving His 373, Tyr 254, flavin N5 and O4, a heme
      propionate, and solvent molecules, and/or electrostatic interactions with Asp 282
      and with the reduced cofactor N1 anion. In this work, we probe the effect of the
      hydrogen bond network at the active site by studying proton exchange with solvent
      for 2 mutants: Y254F and the recombinant flavodehydrogenase domain, in which this
      network should be disrupted. The rate of proton exchange, as determined by
      intermolecular hydrogen transfer experiments, appears identical in the
      flavodehydrogenase domain and the wild-type enzyme, whereas it is about 3-fold
      faster in the Y254F mutant. It thus appears that specific hydrogen bonds to the
      solvent do not play a major role in stabilizing the acid form of His 373 in
      reduced flavocytochrome b2. Removal of the Y254 phenol group induces a pKa drop
      of about half a pH unit for His 373 in the reduced enzyme. Even then, the rate of
      exchange of the imidazolium proton with solvent is still lower by several orders
      of magnitude than that of a normally ionizing histidine. Other factors must then
      also contribute to the pKa increase, such as the electrostatic interactions with
      D282 and the anionic reduced cofactor, as suggested by the crystal structure.

PMID- 8142888
TI  - Positions of His-64 and a bound water in human carbonic anhydrase II upon binding
      three structurally related inhibitors.
AB  - The 3-dimensional structure of human carbonic anhydrase II (HCAII; EC 4.2.1.1)
      complexed with 3 structurally related inhibitors, 1a, 1b, and 1c, has been
      determined by X-ray crystallographic methods. The 3 inhibitors (1a = C8H12N2O4S3)
      vary only in the length of the substituent on the 4-amino group: 1a, proton; 1b,
      methyl; and 1c, ethyl. The binding constants (Ki's) for 1a, 1b, and 1c to HCAII
      are 1.52, 1.88, and 0.37 nM, respectively. These structures were solved to learn
      if any structural cause could be found for the difference in binding. In the
      complex with inhibitors 1a and 1b, electron density can be observed for His-64
      and a bound water molecule in the native positions. When inhibitor 1c is bound,
      the side chain attached to the 4-amino group is positioned so that His-64 can
      only occupy the alternate position and the bound water is absent. While a variety
      of factors contribute to the observed binding constants, the major reason 1c
      binds tighter to HCAII than does 1a or 1b appears to be entropy: the increase in
      entropy when the bound water molecule is released contributes to the increase in
      binding and overcomes the small penalty for putting the His-64 side chain in a
      higher energy state.

PMID- 8142889
TI  - Studies on the specificity of acetylaminoacyl-peptide hydrolase.
AB  - In a continuing attempt to explore the types of specificity determinants that may
      affect protein-protein (peptide) interactions, a number of short (2-5 residues)
      acetylated peptides have been compared as substrates for the enzyme
      acetylaminoacyl-peptide hydrolase (EC 3.4.19.1). The reference substrate was Ac
      AAAA, and most of the other substrates were derived from this basic structure by
      single amino acid substitutions. The Km and kcat for the different substrates
      were determined by standard steady-state kinetics, and the corresponding delta
      delta GT++ value derived from kcat/Km was used for the comparison, setting delta
      detal GT++ for Ac-AAAA equal to 0. The best substrates were found to be those
      containing negative charges (Asp > Glu) or aromatic residues in positions 1', 2',
      or 3' (delta delta GT++ values of 2-5 kJ); the negative charge provided by the C
      terminus of the substrate also appears to be important, since the amide and O-Me
      ester derivatives caused a change in delta delta GT++ values of -7 to -8 kJ from
      the reference peptide. The stimulating effect of the negative charges is
      consistent with the inhibitory effect of positive charges in similar peptides
      (Krishna RG, Wold F, 1992, Protein Sci 1:582-589), and the proposed active site
      model incorporates subsites for both charge-charge and hydrophobic interactions.
      In assessing all the data, it is clear that the properties of the individual
      substrates reflect the total make-up of each peptide and not only the effect of a
      single residue in a given position.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142890
TI  - Construction of an overproduction vector containing the novel srp (sterically
      repressed) promoter.
AB  - We report the design, synthesis, and evaluation of a novel Escherichia coli
      promoter intended for use in overproduction of proteins that are deleterious to
      the host. In this sterically repressed promoter (srp), the lac operator site is
      positioned between the -10 and -35 elements, where it can interfere sterically
      with RNA polymerase and thereby prevent assembly of a poised transcriptional
      complex. An srp-containing phagemid, pKEN1, and a tac-containing phagemid, pHN1,
      which has been widely used in protein overproduction but is often unstable, are
      compared with respect to levels of uninduced and induced protein expression. The
      level of uninduced protein synthesis by the srp promoter in vivo is approximately
      50% of that observed with tac, whereas the levels of induced protein synthesis
      with the 2 vectors are approximately equal. A remarkable increase in stability of
      overproduction and growth was observed when the toxic Ada protein was
      overproduced in pKEN1, demonstrating the potential utility of this vector in
      overproducing toxic proteins.

PMID- 8142891
TI  - Identification of succinimide sites in proteins by N-terminal sequence analysis
      after alkaline hydroxylamine cleavage.
AB  - Under favorable conditions, Asp or Asn residues can undergo rearrangement to a
      succinimide (cyclic imide), which may also serve as an intermediate for
      deamidation and/or isoaspartate formation. Direct identification of such
      succinimides by peptide mapping is hampered by their lability at neutral and
      alkaline pH. We determined that incubation in 2 M hydroxylamine, 0.2 M Tris
      buffer, pH 9, for 2 h at 45 degrees C will specifically cleave on the C-terminal
      side of succinimides without cleavage at Asn-Gly bonds; yields are typically
      approximately 50%. N-terminal sequence analysis can then be used to identify an
      internal sequence generated by cleavage of the succinimide, hence identifying the
      succinimide site.

PMID- 8142892
TI  - Investigation of the backbone dynamics of the IgG-binding domain of streptococcal
      protein G by heteronuclear two-dimensional 1H-15N nuclear magnetic resonance
      spectroscopy.
AB  - The backbone dynamics of the immunoglobulin-binding domain (B1) of streptococcal
      protein G, uniformly labeled with 15N, have been investigated by two-dimensional
      inverse detected heteronuclear 1H-15N NMR spectroscopy at 500 and 600 MHz. 15N
      T1, T2, and nuclear Overhauser enhancement data were obtained for all 55 backbone
      NH vectors of the B1 domain at both field strengths. The overall correlation time
      obtained from an analysis of the T1/T2 ratios was 3.3 ns at 26 degrees C.
      Overall, the B1 domain is a relatively rigid protein, consistent with the fact
      that over 95% of the residues participate in secondary structure, comprising a
      four-stranded sheet arranged in a -1, +3x, -1 topology, on top of which lies a
      single helix. Residues in the turns and loops connecting the elements of
      secondary structure tend to exhibit a higher degree of mobility on the picosecond
      time scale, as manifested by lower values of the overall order parameter. A
      number of residues at the ends of the secondary structure elements display two
      distinct internal motions that are faster than the overall rotational correlation
      time: one is fast (< 20 ps) and lies in the extreme narrowing limit, whereas the
      other is one to two orders of magnitude slower (1-3 ns) and lies outside the
      extreme narrowing limit. The slower motion can be explained by large-amplitude
      (20-40 degrees) jumps in the N-H vectors between states with well-defined
      orientations that are stabilized by hydrogen bonds.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8142893
TI  - The Northrop hypothesis and the origins of a virus-induced enzyme.

PMID- 8142894
TI  - Hydrogen bond interactions of G proteins with the guanine ring moiety of guanine
      nucleotides.
AB  - We have utilized Raman difference spectroscopy to investigate hydrogen bonding
      interactions of the guanine moiety in guanine nucleotides with the binding site
      of two G proteins, EF-Tu (elongation factor Tu from Escherichia coli) and the c
      Harvey ras protein, p21 (the gene product of the human c-H-ras proto-oncogene).
      Raman spectra of proteins complexed with GDP (guanosine 5' diphosphate), IDP
      (inosine 5' diphosphate), 6-thio-GDP, and 6-18O-GDP were measured, and the
      various difference spectra were determined. These were compared to the difference
      spectra obtained in solution, revealing vibrational features of the nucleotide
      that are altered upon binding. Specifically, we observed significant frequency
      shifts in the vibrational modes associated with the 6-keto and 2-amino positions
      of the guanine group of GDP and IDP that result from hydrogen bonding
      interactions between these groups and the two proteins. These shifts are
      interpreted as being proportional to the local energy of interaction (delta H)
      between the two groups and protein residues at the nucleotide binding site.
      Consistent with the tight binding between the nucleotides and the two proteins,
      the shifts indicate that the enthalpic interactions are stronger between these
      two polar groups and protein than with water. In general, the spectral shifts
      provide a rationale for the stronger binding of GDP and IDP with p21 compared to
      EF-Tu. Despite the structural similarity of the binding sites of EF-Tu and p21,
      the strengths of the observed hydrogen bonds at the 6-keto and 2-amino positions
      vary substantially, by up to a factor of 2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142895
TI  - G proteins: critical control points for transmembrane signals.
AB  - Heterotrimeric GTP-binding proteins (G proteins) that are made up of alpha and
      beta gamma subunits couple many kinds of cell-surface receptors to intracellular
      effector enzymes or ion channels. Every cell contains several types of receptors,
      G proteins, and effectors. The specificity with which G protein subunits interact
      with receptors and effectors defines the range of responses a cell is able to
      make to an external signal. Thus, the G proteins act as a critical control point
      that determines whether a signal spreads through several pathways or is focused
      to a single pathway. In this review, I will summarize some features of the
      structure and function of mammalian G protein subunits, discuss the role of both
      alpha and beta gamma subunits in regulation of effectors, the role of the beta
      gamma subunit in macromolecular assembly, and the mechanisms that might make some
      responses extremely specific and others rather diffuse.

PMID- 8142896
TI  - Structural analysis and localization of the carbohydrate moieties of a soluble
      human interferon gamma receptor produced in baculovirus-infected insect cells.
AB  - A soluble form of the human interferon gamma receptor that is required for the
      identification of interferon gamma antagonists was expressed in baculovirus
      infected insect cells. The protein carried N-linked carbohydrate and showed a
      heterogeneity on denaturing polyacrylamide gels. We investigated the utilization
      of the potential sites for N-linked glycosylation and the structure of the
      carbohydrate moieties of this soluble receptor. Amino acid sequence analysis and
      ion spray mass spectrometry revealed that of the five potential sites for N
      linked glycosylation, Asn17 and Asn69 were always utilized, whereas Asn62 and
      Asn162 were utilized in approximately one-third of the protein population. Asn223
      was never found to be glycosylated. The soluble receptor was treated with N
      glycosidase F and the oligosaccharides released were analyzed by matrix-assisted
      laser desorption mass spectrometry, which showed that the protein carried six
      types of short carbohydrate chains. The predominant species was a hexasaccharide
      of molecular mass 1,039, containing a fucose subunit linked to the proximal N
      acetylglucosamine residue: [formula: see text]

PMID- 8142897
TI  - Structural investigation of catalytically modified F120L and F120Y semisynthetic
      ribonucleases.
AB  - The structures of two catalytically modified semisynthetic RNases obtained by
      replacing phenylalanine 120 with leucine and tyrosine have been determined and
      refined at a resolution of 2.0 A (R = 0.161 and 0.184, respectively). These
      structures have been compared with the refined 1.8-A structure (R = 0.204) of the
      fully active phenylalanine-containing enzyme (Martin PD, Doscher MS, Edwards BFP,
      1987, J Biol Chem 262:15930-15938) and with the catalytically defective D121A
      (2.0 A, R = 0.172) and D121N (2.0 A, R = 0.186) analogs (deMel VSJ, Martin PD,
      Doscher MS, Edwards BFP, 1992, J Biol Chem 267:247-256). The movement away from
      the active site of the loop containing residues 65-72 is seen in all three
      catalytically defective analogs--F120L, D121A, and D121N--but not in the fully
      active (or hyperactive) F120Y. The insertion of the phenolic hydroxyl of Tyr 120
      into a hydrogen-bonding network involving the hydroxyl group of Ser 123 and a
      water molecule in F120Y is the likely basis for the hyperactivity toward uridine
      2',3'-cyclic phosphate previously found for this analog (Hodges RS, Merrifield
      RB, 1974, Int J Pept Protein Res 6:397-405) as well as the threefold increase in
      KM for cytidine 2',3'-cyclic phosphate found for this analog by ourselves.

PMID- 8142898
TI  - Structure of the membrane channel porin from Rhodopseudomonas blastica at 2.0 A
      resolution.
AB  - The crystal structure of a membrane channel, homotrimeric porin from
      Rhodopseudomonas blastica has been determined at 2.0 A resolution by multiple
      isomorphous replacement and structural refinement. The current model has an R
      factor of 16.5% and consists of 289 amino acids, 238 water molecules, and 3
      detergent molecules per subunit. The partial protein sequence and subsequently
      the complete DNA sequence were determined. The general architecture is similar to
      those of the structurally known porins. As a particular feature there are 3
      adjacent binding sites for n-alkyl chains at the molecular 3-fold axis. The side
      chain arrangement in the channel indicates a transverse electric field across
      each of the 3 pore eyelets, which may explain the discrimination against nonpolar
      solutes. Moreover, there are 2 significantly ordered girdles of aromatic residues
      at the nonpolar/polar borderlines of the interface between protein and membrane.
      Possibly, these residues shield the polypeptide conformation against adverse
      membrane fluctuations.

PMID- 8142899
TI  - Crystal structure of the unactivated ribulose 1,5-bisphosphate
      carboxylase/oxygenase complexed with a transition state analog, 2-carboxy-D
      arabinitol 1,5-bisphosphate.
AB  - The crystal structure of unactivated ribulose 1,5-bisphosphate
      carboxylase/oxygenase from Nicotiana tabacum complexed with a transition state
      analog, 2-carboxy-D-arabinitol 1,5-bisphosphate, was determined to 2.7 A
      resolution by X-ray crystallography. The transition state analog binds at the
      active site in an extended conformation. As compared to the binding of the same
      analog in the activated enzyme, the analog binds in a reverse orientation. The
      active site Lys 201 is within hydrogen bonding distance of the carboxyl oxygen of
      the analog. Loop 6 (residues 330-339) remains open and flexible upon binding of
      the analog in the unactivated enzyme, in contrast to the closed and ordered loop
      6 in the activated enzyme complex. The transition state analog is exposed to
      solvent due to the open conformation of loop 6.

PMID- 8142900
TI  - Solution structure of villin 14T, a domain conserved among actin-severing
      proteins.
AB  - The solution structure of the N-terminal domain of the actin-severing protein
      villin has been determined by multidimensional heteronuclear resonance
      spectroscopy. Villin is a member of a family of actin-severing proteins that
      regulate the organization of actin in the eukaryotic cytoskeleton. Members of
      this family are built from 3 or 6 homologous repeats of a structural domain of
      approximately 130 amino acids that is unrelated to any previously known
      structure. The N-terminal domain of villin (14T) contains a central beta-sheet
      with 4 antiparallel strands and a fifth parallel strand at one edge. This sheet
      is sandwiched between 2 helices on one side and a 2-stranded parallel beta-sheet
      with another helix on the other side. The strongly conserved sequence
      characteristic of the protein family corresponds to internal hydrophobic
      residues. Calcium titration experiments suggest that there are 2 binding sites
      for Ca2+, a stronger site near the N-terminal end of the longest helix, with a Kd
      of 1.8 +/- 0.4 mM, and a weaker site near the C-terminal end of the same helix,
      with a Kd of 11 +/- 2 mM. Mutational and biochemical studies of this domain in
      several members of the family suggest that the actin monomer binding site is near
      the parallel strand at the edge of the central beta-sheet.

PMID- 8142901
TI  - Two conformational states of Candida rugosa lipase.
AB  - The structure of Candida rugosa lipase in a new crystal form has been determined
      and refined at 2.1 A resolution. The lipase molecule was found in an inactive
      conformation, with the active site shielded from the solvent by a part of the
      polypeptide chain-the flap. Comparison of this structure with the previously
      determined "open" form of this lipase, in which the active site is accessible to
      the solvent and presumably the substrate, shows that the transition between these
      2 states requires only movement of the flap. The backbone NH groups forming the
      putative oxyanion hole do not change position during this rearrangement,
      indicating that this feature is preformed in the inactive state. The 2 lipase
      conformations probably correspond to states at opposite ends of the pathway of
      interfacial activation. Quantitative analysis indicates a large increase of the
      hydrophobic surface in the vicinity of the active site. The flap undergoes a
      flexible rearrangement during which some of its secondary structure refolds. The
      interactions of the flap with the rest of the protein change from mostly
      hydrophobic in the inactive form to largely hydrophilic in the "open"
      conformation. Although the flap movement cannot be described as a rigid body
      motion, it has very definite hinge points at Glu 66 and at Pro 92. The
      rearrangement is accompanied by a cis-trans isomerization of this proline, which
      likely increases the energy required for the transition between the 2 states, and
      may play a role in the stabilization of the active conformation at the
      water/lipid interface. Carbohydrate attached at Asn 351 also provides
      stabilization for the open conformation of the flap.

PMID- 8142902
TI  - Response of dynamic structure to removal of a disulfide bond: normal mode
      refinement of C77A/C95A mutant of human lysozyme.
AB  - In order to investigate the response of dynamic structure to removal of a
      disulfide bond, the dynamic structure of human lysozyme has been compared to its
      C77A/C95A mutant. The dynamic structures of the wild type and mutant are
      determined by normal mode refinement of 1.5-A-resolution X-ray data. The
      C77A/C95A mutant shows an increase in apparent fluctuations at most residues.
      However, most of the change originates from an increase in the external
      fluctuations, reflecting the effect of the mutation on the quality of crystals.
      The effects of disulfide bond removal on the internal fluctuations are almost
      exclusively limited to the mutation site at residue 77. No significant change in
      the correlation of the internal fluctuations is found in either the overall or
      local dynamics. This indicates that the disulfide bond does not have any
      substantial role to play in the dynamic structure. A comparison of the wild-type
      and mutant coordinates suggests that the disulfide bond does not prevent the 2
      domains from parting from each other. Instead, the structural changes are
      characteristic of a cavity-creating mutation, where atoms surrounding the
      mutation site move cooperatively toward the space created by the smaller alanine
      side chain. Although this produces tighter packing, more than half of the cavity
      volume remains unoccupied, thus destabilizing the native state.

PMID- 8142903
TI  - DNA bending by nuclear receptors.
AB  - Although steroid hormone receptors constitute an intensively studied family of
      ligand-regulated transcription factors, the mechanism by which these receptors
      activate transcription has not been defined. Evidence has accumulated from
      prokaryotic and eukaryotic systems that many transcription factors are capable of
      binding to their cognate recognition sequences and causing DNA to bend.
      Therefore, it has been hypothesized that DNA bending and transcription activation
      may be functionally coupled. We have utilized circular permutation analysis to
      examine the ability of the estrogen receptor DNA binding domain and the intact
      estrogen receptor to bend DNA fragments containing estrogen response elements
      (EREs). The DNA binding domain, which is a less potent activator of
      transcription, bent ERE containing DNA fragments less (34 degrees) than the
      intact estrogen receptor (56 degrees), which is a more potent activator of
      transcription. In addition, when two EREs were present in a DNA fragment, the
      degree of DNA bending observed was greater than when one ERE was present. These
      data suggest that DNA bending may play a role in transcription activation of
      estrogen responsive genes.

PMID- 8142904
TI  - Nuclear protein kinase C and signal transduction.
AB  - Protein kinase C (pKC) is a family of enzymes, consisting of ten isoenzymes. Some
      of the members of the pKC family are not dependent on calcium for their activity
      and also do not bind diacylglycerol. Protein kinase C is either translocated to
      the nucleus or present endogenously. Both calcium-dependent as well as calcium
      independent isoenzymes are located in the nucleus. Protein kinase C has specific
      functions in the events activated within the nucleus during signal transduction.
      Three lines of approach have been taken to discern the nuclear function of pKC:
      pathways of activation of cytosolic pKC regulating nuclear events; translocation
      of pKC to the nucleus from the cytosol, and activation of native pKC in isolated
      nuclei. Protein kinase C contains a nuclear targeting bipartite motif and has a
      role in the nuclear calcium signaling process. Targeting and binding of pKC to
      the sites of replicational and posttranscriptional activity may be one of the
      mechanisms of the pKC signaling process. Protein kinase C-mediated activation of
      nuclear phosphatases and dephosphorylation of target nuclear proteins are the
      areas where much less attention has been paid. Exploring these avenues may lead
      to new insights into the molecular mechanism of nuclear signal transduction.

PMID- 8142905
TI  - Nontranscriptional effects of steroid hormones.
AB  - A growing body of literature exists documenting the nonnuclear effects of steroid
      hormones, and in particular, binding of the lipophillic ligands to specific
      plasmalemmal recognition sites. This review compiles evidence supporting the
      presence of membrane receptors for extradiol 17 beta, progesterone,
      corticosteroids, thyroid hormone, and 1,25-dihydroxyvitamin D3. In addition, 1,25
      dihydroxyvitamin D3-mediated nonnuclear signal transduction mechanisms and
      physiological responses are discussed.

PMID- 8142906
TI  - Heat stressing stimulates nuclear protein kinase C raising diacylglycerol levels.
      Nuclear protein kinase C activation precedes Hsp70 mRNA expression.
AB  - Protein kinase C (pKC) activity has been studied in rat liver after subjecting
      animals to heat shocking. Nuclear pKC activity was stimulated owing to heat
      shocking without any change in the cytosolic enzyme activity. The nuclear
      diacylglycerol levels were raised owing to heat stress along with the stimulation
      of polarhead phospholipid hydrolysis. Kinetically, the Vmax of nuclear pKC was
      enhanced as a result of heat shocking, with no change in apparent Km and with
      concomitant phosphorylation of nuclear lamin B2. Western blot analysis as well as
      phorbol dibutyrate binding indicate that pKC protein levels did not change
      because of heat shocking. The stimulation of nuclear pKC under heat stress
      conditions represents an in vivo phenomenon and the enzymes stimulation precedes
      Hsp70 mRNA expression.

PMID- 8142907
TI  - Modeling of the lectin-homology domains of the human and murine low-affinity Fc
      epsilon receptor (Fc epsilon RII/CD23).
AB  - Models of the lectin-homology domains of the human and murine low-affinity
      receptors for IgE (Fc epsilon RII/CD23) were built on the basis of sequence
      similarity with rat mannose-binding protein, the structure of which is known. The
      sites on Fc epsilon RII/CD23 that are possibly involved in the interaction with
      IgE and with another ligand, CD21/CR2, are proposed. The models may assist the
      design of protein engineering experiments for the study of the reactivity of
      these molecules.

PMID- 8142908
TI  - Correlation of molecular shape with GPIIb-IIIa receptor antagonist activity in
      RGD peptides.
AB  - Arg-Gly-Asp-Ser (RGDS) 1, Arg-Val-Asp-Ser (RVDS) 2, Arg-dVal-Asp-Ser (R[d]VDS) 3,
      and a cyclic RGD peptide, cyclo S,R [H-Pen-Arg-Gly-Asp-Pen-Gly-OH] 4, were tested
      for their ability to antagonize GPIIb-IIIa function. The activities were found to
      fall in the order 4 >> 1 >> 3 > 2. Simulated annealing and molecular dynamics
      studies were carried out to estimate the most populated conformations of each
      molecule. The acyclic molecules 1-3 were found to populate a much wider range of
      conformations than the cyclic molecule 4. The backbones of all four molecules
      were found to approximate beta-turn structures in the most populated
      conformations. In 4 the beta-turn intramolecular hydrogen bond between C = O of
      the i residue (Arg) and NH of the i + 3 residue (Ser) did not appear to be
      present. The distance between the beta-carbons of the critical Arg and Asp groups
      was found to be shorter in 4 (average 7.98 A) than in the less active acyclic
      molecules (averages of 8.65-9.33 A).

PMID- 8142909
TI  - Health care reform: where will case management fit in?

PMID- 8142910
TI  - Service utilization among older people with AIDS: implications for case
      management.
AB  - People over 50 years of age have consistently comprised 10% of all cases
      diagnosed with AIDS in the United States. Older people with AIDS have been found
      to differ both in the clinical course of the disease as well as in their need for
      services. A comparison of 49 patients, 10 of whom were over age 50, revealed that
      older persons were more functionally impaired at the time of enrollment in a home
      care program than those under 50 years. Additionally, older individuals were less
      likely to utilize emotional support services commonly offered by the AIDS network
      than are their younger counterparts.

PMID- 8142911
TI  - Case management in two long-term-care populations: a synthesis of research.
AB  - This article synthesizes case management research for two long-term care
      populations and compares the implications for practice, program, and policy
      development. The two populations are chronically mentally ill adults and
      functionally limited older adults. The findings are a synthesis of 137 empirical
      investigations of case management. The synthesis distinguishes three major
      variables related to case management for these populations: (a) the goals or
      outcome variables for case management may affect the timing of case management
      services and the course of care for each population; (b) the availability and
      function of informal supports is developmentally different for the two groups;
      and (c) there is a need for varying constellations of services for different long
      term-care populations.

PMID- 8142912
TI  - Case management in Alzheimer's disease.
AB  - Patients with a diagnosis of Alzheimer's disease and their families need the
      assistance of a case manager to deal with the issues of long-term care. The case
      manager assists with education, planning, linking to formal and informal
      resources, and addressing emotional needs in the family unit. This article
      discusses specific suggestions to address problems in the three stages of
      Alzheimer's disease from the time of medical diagnosis to the end of life.

PMID- 8142913
TI  - Case management activities for the rural elderly: findings from a national study.
AB  - This article presents an overview of case management activities for rural elders
      in the United States through an analysis of data collected from 553 case
      management providers in late 1990. Information about the following areas is
      presented: type of organization; number of staff and its educational background;
      definitions and goals of case management; elements of the case management
      process; record keeping and quality assurance; client characteristics and program
      targeting; and program size and funding. Conclusions and policy issues supported
      by the data are noted as are future research areas.

PMID- 8142914
TI  - A college-managed nursing center offers training in case management for nursing
      students.
AB  - The College of Nursing, State University of New York Health Science Center at
      Brooklyn, operates a nursing center in conjunction with a nonprofit social work
      agency. Health support services are delivered to frail elderly individuals in
      their homes or at the Nursing Center, free of charge, using an interdisciplinary
      case management model. In this model, case management is provided by graduate
      students and faculty with undergraduate students forming part of the health care
      team. This article describes the model and provides two case study examples that
      demonstrate its interdisciplinary focus, value as a training mechanism, and scope
      of case management services.

PMID- 8142916
TI  - Immune ablation followed by allogeneic or autologous bone marrow transplantation:
      a new treatment for severe autoimmune diseases?

PMID- 8142915
TI  - Stem cell responses in myelosuppressed mice following sequential treatment with
      recombinant human interleukin 1 (rHuIL-1), recombinant murine interleukin 3
      (rMuIL-3) and recombinant human macrophage colony-stimulating factor (rHuM-CSF).
AB  - In vivo, recombinant human interleukin 1 alpha (rHuIL-1 alpha) + recombinant
      human macrophage colony-stimulating factor (rHuM-CSF) (IL-1 + M-CSF) effectively
      serves as a rescue agent for myelosuppression by enhancing the recovery of
      hematopoietic stem cell (HSC) subpopulations following treatment with 5
      fluorouracil (5-FU). Because in vitro studies have suggested that hematopoietic
      recovery in 5-FU-treated bone marrow (FUBM) may proceed from a 5-FU resistant,
      (IL-1 + IL-3 + M-CSF-responsive) high proliferative potential HSC subpopulation
      of colony forming cells (HPP-CFC), studies were carried out to determine whether
      the addition of recombinant murine interleukin 3 (rMuIL-3) (IL-3) to either IL-1
      or IL-1 + M-CSF would further enhance the recovery of HSC subpopulations in
      myelosuppressed C57Bl/6 mice. With the exception of the HPP-CFC, IL-3 dampened,
      rather than enhanced, the accelerated recovery of 8 d and 12 d colony forming
      units-spleen (8 d and 12 d CFU-S) and the committed macrophage progenitor (CFU-M)
      associated with in vivo treatment with IL-1 alone. Similarly, IL-3 interfered
      with the enhanced recovery of those HSC subpopulations in FUBM influenced by the
      synergistic interaction of IL-1 + M-CSF. This interference, however, was observed
      only when the rMuIL-3 was administered on day 2 or 3 of a four-day treatment with
      IL-1 + M-CSF. There was, however, no evidence that IL-3 exerted a negative
      influence on the restoration of granulocytes in the myelosuppressed animals.
      Moreover, sequencing studies provided data suggesting that the dampening effects
      of IL-3 on the synergistic interaction of IL-1 + M-CSF resulted from both an
      enhanced differentiation of the more primitive HSC subpopulations and a
      significant, but preferential, mobilization of the more mature 8 d CFU-S and CFU
      M to extramedullary organs and that the mobilization of these more mature HSC
      subpopulations was temporally linked to their generation from the recovering HPP
      CFC and 12 d CFU-S subpopulations.

PMID- 8142917
TI  - Predictive statistics and artificial intelligence in the U.S. National Cancer
      Institute's Drug Discovery Program for Cancer and AIDS.
AB  - The National Cancer Institute's drug discovery program screens more than 20,000
      chemical compounds and natural products a year for activity against a panel of 60
      tumor cell lines in vitro. The result is an information-rich database of patterns
      that form the basis for what we term an "information-intensive" approach to the
      process of drug discovery. The first step was a demonstration, both by
      statistical methods (including the program COMPARE) and by neural networks, that
      patterns of activity in the screen can be used to predict a compound's mechanism
      of action. Given this finding, the overall plan has been to develop three large
      matrices of information: the first (designated A) gives the pattern of activity
      for each compound tested against each cell line in the screen; the second (S)
      encodes any of a number of types of 2-D or 3-D structural motifs for each
      compound; the third (T) indicates each cell's expression of molecular targets
      (e.g., from 2-dimensional protein gel electrophoresis). Construction and updating
      of these matrices is an ongoing process. The matrices can be concatenated in
      various ways to test a variety of specific hypotheses about compounds screened,
      as well as to "prioritize" candidate compounds for testing. To aid in these
      efforts, we have developed the DISCOVERY program package, which integrates the
      matrix data for visual pattern recognition. The "information-intensive" approach
      summarized here in some senses serves to bridge the perceived gap between
      screening and structure-based drug design.

PMID- 8142918
TI  - The use of animal models in cancer drug discovery and development.
AB  - The process of searching for new cancer drugs has evolved from rational
      empiricism using high volume murine screens towards more targeted systems
      designed to discover agents which are specifically active against the common
      solid tumors of adulthood. Irrespective of the method of discovery, animal models
      are necessary in cancer drug development to answer fundamental questions of drug
      pharmacology and end organ toxicity. This knowledge is fundamental to the design
      of Phase I clinical trials. Increasingly, animal models are being utilized in the
      earliest stages of cancer drug discovery, as well as finding new uses guiding
      dose escalation in man. In addition, transgenic and SCID model systems have
      special applicability to the preclinical and clinical development of biological
      agents. This article reviews the emerging roles of animal models in cancer drug
      discovery and development.

PMID- 8142919
TI  - Anti-tumorigenic chalcones.
AB  - On the basis of our recent findings that licochalcone A isolated from Xin-jiang
      licorice showed anti-inflammatory and anti-tumorigenic activities, we synthesized
      more than 40 chalcone derivatives to examine their anti-tumorigenic activities.
      In vitro inhibitory activity against phosphorylation of phospholipids promoted by
      tetradecanoylphorbol-13-acetate (TPA) in HeLa cells was adopted as a screening
      test for anti-tumor-promoting effect. In vivo experimental mouse skin tumors
      initiated by dimethylbenz[a]-anthracene (DMBA) and promoted by TPA were used to
      test the anti-tumor-promoting effect of chalcones. In the results, 3'- and 4'
      methyl-3-hydroxychalcone showed the highest potency in inhibiting tumorigenesis.
      They also showed a remarkable inhibitory effect on the proliferation of HGC-27
      cells derived from human gastric cancer. We discuss the structure-activity
      relationship, including stereo-chemical phototransformation, of some chalcone
      derivatives with reference to their ultraviolet (UV) and nuclear magnetic
      resonance (NMR) spectroscopic data.

PMID- 8142920
TI  - Highlight on the studies of anticancer drugs derived from plants in China.
AB  - Recent progress on the study of anticancer drugs originating from plants in China
      is reviewed in this paper. Guided by the experience of traditional Chinese
      medicine, several new drugs have been found. Indirubin from Indigofera tinctoria
      is useful for the treatment of chronic myelocytic leukemia. Irisquinone from Iris
      latea pallasii and 10-hydroxy camptothecin from Camptotheca accuminata have
      exhibited definite activity on rodent tumors. Recent studies indicate that
      ginsenoside Rh2 is an inducer of cell differentiation in melanoma B-16 cells in
      vitro. Pharmacological studies have demonstrated that curcumin from Curcuma longa
      is an antimutagen as well as an antipromotor for cancer. Daidzein and acetyl
      boswellic acid have been shown to be effective inducers of cell differentiation
      in HL-60 cells. Guided by the chemotaxonomic principle of plants, harringtonine
      and homoharringtonine isolated from Cephalotaxus hainanesis have exhibited
      significant antileukemia activity and are widely used in clinics in China. Taxol
      from Taxus chinensis has been shown to be an important new anticancer drug with
      unique chemical structure and mechanism of action. The continuous search for new
      anticancer drugs from plants will be a fruitful frontier in cancer treatment and
      chemoprevention.

PMID- 8142921
TI  - Plant-derived drugs acting on cellular Ca2+ mobilization in vascular smooth
      muscle: tetramethylpyrazine and tetrandrine.
AB  - The pharmacological profiles of the active ingredients extracted and purified
      from two well-known Chinese traditional medicinal plants were reviewed. These
      herbal drugs include tetramethylpyrazine (TMP) and tetrandrine (TET); both have
      been clinically used in China for the treatment of cardiovascular diseases due to
      their vasodilatory actions. Studies from this laboratory have confirmed
      previously reported characteristics of TMP as a Ca2+ antagonist in vascular
      tissues. However, it also elicited inhibitory effects in response to a wide
      variety of receptor stimulations as indicated by functional studies and
      radioligand binding studies using isolated subcellular membranes. TET also
      inhibited the vascular contraction in response to depolarization by KCl and
      phenylephrine. It has been found to interact directly with the L-type Ca2+
      channel and alpha-adrenoceptor subtypes. Recently, its action on T-type Ca2+
      channels has also been demonstrated. These findings collectively suggest that
      studies of the vasodilatory and antihypertensive effects of these plant-derived
      drugs on the regulation of cytosolic Ca2+ in vascular smooth muscle are
      consistent with the current hypothesis of Ca2+ dysfunction as an important
      etiological factor for the pathogenesis of hypertension.

PMID- 8142922
TI  - Mass spectrometry in the development of drugs from traditional medicines.
AB  - The mass spectrometer ionizes molecules to separate and weigh the resulting
      molecular ions and their dissociation products. These product masses indicate
      directly the sequence of constituents of the original molecule, such as amino
      acids in proteins or bases in nucleotides. Because single ions can be detected,
      even subfemtomole sensitivities are possible. In tandem mass spectrometry
      (MS/MS), molecular ions from a mixture can be separated to isolate ions of a
      specific component, whose further dissociation can then give structural
      information on that component. Electrospray ionization and other recently
      developed methods make possible the ionization of biomolecules even larger than
      100 kDa. The Fourier-transfer mass spectrometer has unusual capabilities for
      measuring ions over a 100 kDa mass range simultaneously at unit resolution for
      MS/MS applications utilizing subfemtomole sample quantities.

PMID- 8142923
TI  - The design and synthesis of a new anticancer drug based on a natural product lead
      compound: from neplanocin A to cyclopentenyl cytosine (CPE-C).
AB  - In 1979, an unusual, carbocyclic nucleoside was discovered in a Japanese
      fermentation broth and designated neplanocin A. This compound is an analog of
      adenosine possessing a cyclopentene-containing "sugar" glycon. Although
      neplanocin A was biologically active, it was quite toxic. It therefore became a
      lead compound for analog synthesis in an attempt to maximize antitumor and
      antiviral activity while minimizing toxicity. First, a total synthesis of
      naturally occurring (-)-neplanocin A was accomplished using a new, versatile
      cyclopentenone carbocyclic "sugar" intermediate. This intermediate was then used
      to synthesize some 20 purine and pyrimidine analogs of neplanocin A which were
      evaluated for their antitumor and antiviral properties. Among the purine analogs,
      3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase,
      was found to have excellent antiviral activity both in vitro and in vivo.
      Cyclopentenyl cytosine (CPE-C) was found to be the most biologically active
      compound among the carbocyclic pyrimidine nucleosides. In addition to activity
      against over 20 viruses, this compound had excellent preclinical antitumor
      activity against both murine leukemias and human tumor xenografts. CPE-C is
      currently under clinical evaluation as an anticancer drug.

PMID- 8142924
TI  - Cytokines and oncogenes in cellular interactions of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic systemic disorder of unknown etiology.
      Most of its debilitation sequelae are derived from progressive destruction of
      joints. The affected joints exhibit inflammation, abnormal immune responses and
      synovial hyperplasia. Although growth factors and cytokines derived from
      macrophages and endothelial cells contribute to the perpetuation of the
      inflammatory process, activated transformed-appearing synovial fibroblasts
      mediate cartilage and bone destruction. Based on the observation that synovial
      hyperplasia is associated with a transformed-appearing phenotype and an
      upregulated expression of protooncogenes and matrix degrading enzymes, the
      present studies are designed to explore the role of a heretofore unknown (retro)
      virus-like particle in the pathogenesis of RA.

PMID- 8142925
TI  - Effects of gamma-irradiation on the M-CSF-promoter linked to a chloramphenicol
      aminoacyl transferase reporter gene expressed in a clonal murine bone marrow
      stromal cell line.
AB  - The effects of cytokines produced by bone marrow stromal cells on closely
      associated hematopoietic cells constitute a major component of the physiology of
      the hematopoietic microenvironment. A major cytokine produced by marrow stromal
      cells is macrophage colony-stimulating factor (M-CSF). To determine the effect of
      gamma-irradiation on the M-CSF promoter in bone marrow stromal cells, we selected
      a clonal cell line from the C3H/HeJ mouse marrow stromal cell line D2XRII and
      stably transfected a reporter construct containing the murine M-CSF-promoter
      linked to a chloramphenicol aminoacyl transferase (CAT) gene. CAT activity was
      measured at serial time points after gamma-irradiation in vitro to doses between
      500 and 10,000 cGy at a dose rate of 116 cGy/min. D2XRII marrow stromal cells
      treated with phorbol myristate acetate (40 micrograms/ml, four h), demonstrated a
      significant two-fold increase in CAT activity. In contrast, CAT activity measured
      immediately, 24 h, 72 h or 1 week after gamma-irradiation, showed no significant
      increase or decrease in CAT activity. An increase in CAT activity was detected 48
      h after irradiation with cells that received 5,000 cGy. Thus, single fraction
      gamma-irradiation of plateau phase bone marrow stromal cells did not decrease M
      CSF-promoter activity. These results are consistent with prior experimental data
      demonstrating stable levels of release of M-CSF protein following gamma
      irradiation of bone marrow stromal cells and imply that the stability of
      transcription of the gene for this important cytokine is protected from
      irradiation.

PMID- 8142926
TI  - [Free and bound forms of arachidonic acid in the pathogenesis of cerebral edema].

PMID- 8142927
TI  - [Increase in the degree of histone acetylation in the nucleosome sheath leads to
      unfolding of a 30-nm nucleosome fibril].

PMID- 8142928
TI  - [Protective effects of modified glycine in toxicogenic stress].

PMID- 8142929
TI  - [Comparative characteristics of electroretinograms caused by light and x-ray
      stimulation in various adaptation periods].

PMID- 8142930
TI  - [European drug policy].
AB  - The European harmonization of pharmaceutical legislation was completed in 1992,
      but the harmonization of marketing authorizations still requires the creation of
      an "European medicines evaluation agency", From january 1995, two complementary
      marketing authorization procedures will have to be established for human and
      veterinary medicines in the European Community: a decentralised procedure for
      most products, and a centralised procedure, only valid for innovative products.
      At the same time, a better coordination of the assessment of adverse drug
      reactions (pharmacovigilance) should be achieved.

PMID- 8142931
TI  - [Percutaneous transluminal coronary angioplasty].
AB  - Since a decade, new treatments have been developed in the field of Cardiology as
      thrombolysis in acute myocardial infarction, use of angiotension converting
      enzyme inhibitors in cardiac insufficiency, heart transplantation... Percutaneous
      transluminal coronary angioplasty has been developed since 1977. The aim of this
      new technology is to treat myocardial ischemia and appears complementary to
      coronary artery bypass graft.

PMID- 8142932
TI  - [Current clinical aspects of AIDS].
AB  - Our knowledge of the natural history of VIH infection has considerably increased
      during the last years. We know now that clinical evolution will depend of host
      factors as well as of viral characteristics. Among the host factors, the early
      specific cytotoxic response to VIH components plays a major role. Phenotypic
      variation of the virus (syncytium inducer mutants) and viral load in the lymph
      node and in the circulating CD4 cells play also an important role. As far as
      antiviral therapeutic is concerned, at the moment we know that monotherapy with
      nucleosides analogues is probably of limited efficacy because of emergence of
      resistance. Future perspectives include combination of antivirals aimed to
      prevent emergence of resistance and to reduce toxicity.

PMID- 8142933
TI  - Dental implants and human immunodeficiency virus disease.

PMID- 8142934
TI  - Bioactive glass particles of narrow size range: a new material for the repair of
      bone defects.
AB  - A clinical trial to treat dental osseous lesions with bioactive glass granules of
      narrow size range (300 to 360 microns) has been conducted since early spring
      1990. This study followed an animal study in which the osseous tissue repair
      properties of bioactive glass granules of narrow size range and hydroxyapatite
      granules were compared for up to 2 years of implantation. The therapeutic
      response to the bioactive glass material exceeded the response to the
      hydroxyapatite as evidenced by very extensive osteoconduction, as well as the
      capacity to cause differentiation of osteoprogenitor cells to osteoblasts. The
      clinical study was started by virtue of the bioactive glass granules of narrow
      size range eliciting expeditious bone tissue formation throughout a defect. In
      this clinical study 87 patients and 106 defects were treated. The indications
      selected were apical resection areas, cystic defects, extraction sites, and
      defects of the alveolar ridge due to surgery or resorption. After insertion, the
      particles remained well in place and only small changes in the contours of the
      restored defects were seen, at the most up to 2 months postinsertion. At 3 months
      the application sites had fully solidified. Radiographic analysis indicated that
      the material integrated into the bone tissue, and at 6 months any difference
      between glass particles and bone tissue had nearly disappeared. The few initial
      cases with limited clinical results were caused by factors unrelated to the glass
      granules, mostly the surgical technique. By adapting the surgical technique, no
      unfavorable clinical results were subsequently experienced.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8142935
TI  - Bone-grafting materials in implant dentistry.
AB  - There are three classes of bone-grafting materials based upon the mode of action.
      Autogenous bone is an organic material and forms bone by osteogenesis,
      osteoinduction, and osteoconduction. Allografts such as demineralized freeze
      dried bone are osteoinductive and osteoconductive and may be cortical and/or
      trabecular in nature. Alloplasts such as hydroxyapatite and tricalcium phosphate
      may be synthetic or natural, vary in size, and are only osteoconductive. They can
      be divided into three types based upon the porosity of the product and include
      dense, macroporous, and microporous materials. In addition, alloplastic materials
      may be crystalline or amorphous. These materials have different properties and
      therefore indications. The use of the three classes of materials in diverse
      combinations depends upon the size and topography of the bony defect. Small
      defects or defects with four walls of host bone can be repaired with alloplasts
      alone or allografts in combination with alloplasts. The loss of three or more
      bony walls mandates the addition of autogenous bone to the graft or the use of a
      small pore membrane. The larger the defect, the more autogenous bone is required.
      The different indications of bone substitutes are discussed as to their specific
      applications in implant dentistry.

PMID- 8142936
TI  - Finite element analysis of four-abutment Hader bar designs.
AB  - Three-dimensional finite element analyses were conducted on the four-abutment
      Hader bar to determine mechanical properties with respect to bar length,
      stiffener height, and material properties. Three stiffener heights (1, 2, and 3
      mm) were analyzed representing a clinical range of usage. Three material types
      were studied which represent a selection of alloys commonly used clinically. The
      model consisted of a representative Hader bar of 1.8-mm diameter with a 1-mm
      inferior stiffener. The ends of the bar were fixed to a 5-mm diameter coping
      which was attached to a 3.8-mm root form-type implant fixed in a representative
      block of bone. The bone was modeled as fixed at its distal end to eliminate rigid
      body motion. A 200 Newton occlusal force was imposed on the mesial bar and a 450
      Newton force on the distal bar for the three stiffener heights. The results of
      these analyses predicted yielding and fracture (failure) for all 1-mm stiffener
      height and type IV gold alloy cases studied. Stiffener height was found to play a
      strong role in the adequacy of the overall design as compared with changing
      material properties in the range of alloy stiffness tested. Factors of safety
      with respect to static yield strength ranged from 1.44 to 2.12 on the distal
      portion.

PMID- 8142937
TI  - Full arch implant reconstruction in an adolescent patient: clinical report.
AB  - Adolescent patients with partial anodontia can benefit from fixed implant
      treatment. Coordinated multispecialty treatment of a young patient is presented
      and treatment implications are discussed.

PMID- 8142938
TI  - Implant restoration of a hemisected molar: clinical report.
AB  - A retained root and a single root form implant were used to support individual
      crowns to restore a mandibular molar after hemisection. A favorable ratio was
      achieved between the restoration and the root form implant.

PMID- 8142939
TI  - Treatment of buccally placed implants in the edentulous mandible: clinical
      report.
AB  - The restoration of anterior buccally placed implants in an edentulous mandible,
      one of which extended into the movable mucosa of the patient's lip, is presented.
      CeraOne abutments and anterior Rothermann resilient overdenture attachments were
      used to retain the prosthesis.

PMID- 8142940
TI  - Rehabilitation of maxillofacial trauma patients with dental implants.
AB  - Maxillary and mandibular traumatic injuries are inevitable in our society. Dental
      implants can be considered for the replacement of teeth lost as a result of
      trauma, even in complicated cases where associated injuries, such as jaw
      fractures and bone loss, have occurred. Reimbursement for dental services by
      insurance companies in the case of traumatic injuries to the teeth and supporting
      structures is discussed.

PMID- 8142941
TI  - Inferior alveolar nerve repositioning in implant dentistry: clinical report.
AB  - Repositioning the inferior alveolar neurovascular bundle is a high risk procedure
      which can result in permanent damage. It must be justified by the need for
      posterior mandibular support to stabilize the dentition and provide function. A
      clinical report is presented.

PMID- 8142942
TI  - Implant-supported prosthesis between severely tipped teeth: clinical report.
AB  - A restorative solution is presented for dealing with two crowded root form
      implants. When crowding is unavoidable as a result of tipped teeth adjacent to an
      edentulous space, minor modifications in sequence and technique permit an
      otherwise dormant implant to be utilized.

PMID- 8142943
TI  - Validation of the Quality of Life in Depression Scale in a population of adult
      depressive patients aged 60 and above.
AB  - The aim of this study is to evaluate the validity of the Dutch version of the
      Quality of Life in Depression Scale (QLDS) in a population of depressive patients
      aged 60 years and over, who were seen on an outpatient basis by psychiatrists in
      the Flemish region of Belgium. A sample of severely depressive patients was
      followed during an eight-week medical treatment. During this period, each patient
      was evaluated four times with the Hamilton Rating Scale for Depression and with
      the QLDS. We observed that the QLDS was very sensitive to the failing of the
      quality of life in depressive states. The QLDS was also a very good measure of
      change during the improvement of depressives states. Furthermore, the scale
      appears to be very homogeneous across the depressive states range. The results
      are very encouraging, and constitute strong corroboration of the construct
      validity of the scale.

PMID- 8142944
TI  - Long-term pain relief during spinal cord stimulation. The effect of patient
      selection.
AB  - We reviewed our experience with spinal cord stimulation (SCS) in treating 116
      patients with pain in one or both legs. All these patients were selected for an
      initial week of trial stimulation by the criteria: pain due to a known benign
      organic cause, failure of conventional pain control methods and absence of major
      personality disorders. Selected patients included 78 with the Failed Back Surgery
      Syndrome (FBSS), in whom proven correlation existed between the clinical picture
      and the neuroradiological and electromyogram abnormalities. Eighty-four out of
      116 selected patients underwent definitive SCS implantation after 1 week of trial
      stimulation with excellent results (more than 75% pain relief). They were
      followed clinically every 3 months for a mean follow-up period of 47 months.
      Forty-five patients (54%) continued to experience at least 50% of pain relief at
      the latest follow up. Seventy-seven patients (91%) were able to reduce their
      medication intake and 50 patients (60%) reported an improvement in lifestyle.
      FBSS patients responded more positively to the trial stimulation than the other
      patients. However, the later outcome was not affected by patient selection as
      long-term benefit was similar in all definitive SCS patients irrespective of
      aetiology.

PMID- 8142945
TI  - Quality of life assessments in the evaluation of magnetic resonance imaging.
AB  - Health technology assessments incorporating measurement of quality of life are
      becoming increasingly common. In the evaluation of magnetic resonance imaging
      (MRI), the most widely used quality of life instrument has been the Rosser
      classification. The theoretical basis for incorporating such a measure in the
      evaluation of imaging technology is considered and several studies using this
      instrument are reviewed. Despite the obvious technical advances of MRI and its
      influence on clinical management, it has proved difficult to demonstrate that the
      use of this expensive new imaging technique contributes to improvement in health
      related quality of life. Some reasons why the expected improvement has not been
      demonstrated are discussed, as are the quality of life instruments which may be
      appropriate in this setting.

PMID- 8142946
TI  - Proceedings of the inaugural meeting of the International Health-related Quality
      of Life Society, 3-4 February 1994, Brussels, Belgium.

PMID- 8142947
TI  - Criterion validity and reliability of the SF-36 in a population sample.
AB  - This study aimed to determine the criterion validity of the Short Form 36 health
      survey questionnaire (SF-36) in a large community sample, and to explore the
      instrument's internal consistency and validity in groups reporting different
      levels of ill-health. A postal survey was undertaken using a questionnaire
      booklet, containing the SF-36 and a number of other items concerned with
      lifestyles and illness. The questionnaire booklet was sent to 13,042 randomly
      selected subjects between the ages of 18-64 years, drawn from Family Health
      Services Authority (FHSA) computerized registers for Berkshire, Buckinghamshire,
      Northamptonshire and Oxfordshire. This paper is based upon the 9332 (72%)
      responses gained. Scores for the functional status and well-being scales of the
      SF-36 were used as outcome measures. The response rate for the questionnaire
      booklet was 72%. Internal consistency of domains was found to be high, both for
      the sample as a whole, and when broken down by specific subgroups. Criterion
      validity was assessed by comparing scores for the seven multi-item dimensions
      assessing functional status and well being with a single global health question.
      The global question was the first item of the SF-36 and asks respondents to
      evaluate their health 'overall'. Statistically significant trends were observed
      for decreasing SF-36 scores (i.e., those indicating greater health problems) with
      worsening self-rated general health. These results provide further psychometric
      evidence for the use of the SF-36 when used with groups reporting varying extents
      of ill-health.

PMID- 8142948
TI  - Gene transfer efficiency during gestation and the influence of co-transfer of non
      manipulated embryos on production of transgenic mice.
AB  - Litter size of DNA microinjected zygotes is lower than for non-manipulated
      zygotes. The rate of embryonic and fetal survival in early, mid and late
      gestation was determined to assess whether DNA integration was responsible for
      embryonic losses. Also, the effect of including non-microinjected embryos with
      injected embryos on pregnancy rate and transgenic pup production was determined.
      In Experiment 1, one-cell embryos from immature CD-1 mice were microinjected with
      a whey acidic protein promoter-human protein C gene construct. One hour after
      microinjection embryos were transferred to pseudopregnant recipients (45
      transfers of 30 embryos each). Fifteen recipients were sacrificed on day 4, 12
      and 18 of gestation and the embryos/fetuses analysed for the transgene. The
      percentage of embryos or fetuses that were positive for the transgene was not
      significantly different at any day. However, the number of viable embryos at day
      4 was significantly greater than fetuses on days 12 or 18. In addition, a high
      degree of mosaicism was observed in day 18 fetuses and placentae recovered. In
      Experiment 2, one-cell embryos from CD-1 mice were microinjected and co
      transferred with non-manipulated embryos (C57BL/6). Pregnancy rate and the total
      number of pups born were improved by addition of non-injected embryos. However,
      the number of transgenic mice produced was similar whether non-injected embryos
      were included or not. There were 32.2% (15/46) transgenic pups when 0 non
      injected embryos were transferred compared with 15.1% (13/86) transgenic pups
      when 4 or 8 non-injected embryos were added to the transfers. In summary, a high
      degree of embryonic and fetal mortality occurs among microinjected
      embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8142949
TI  - Expression of a human S-adenosylmethionine decarboxylase cDNA in transgenic
      tobacco and its effects on polyamine biosynthesis.
AB  - S-adenosylmethionine decarboxylase (SAMDC; EC 4.1.1.50) is a key regulatory
      enzyme in the polyamine biosynthetic pathway. Numerous studies have shown that
      the enzyme activity and polyamine levels are generally correlated with cellular
      growth in plants, animals and bacteria. In order to gain more insight into the
      role of polyamines in plants, human SAMDC cDNA under control of 35S promoter of
      cauliflower mosaic virus, along with a neomycin phosphotransferase gene, was
      transferred to tobacco (Nicotiana tabacum cv.Xanthi) via Agrobacterium
      tumefaciens. Transgenic plants showed the presence of SAMDC mRNA and a 2-4-fold
      increase in SAMDC activity. In the transformed tissues, putrescine levels were
      significantly reduced, while spermidine content was 2-3 times higher than the
      control tissues. Cellular spermine content was either increased or remained
      unchanged. Excised leaf segments from transformed plants frequently produced
      shoots even on callus inducing medium.

PMID- 8142950
TI  - Opportunities for manipulating the seed protein composition of wheat and barley
      in order to improve quality.
AB  - Wheat and barley are the major temperate cereals, being used for food, feed and
      industrial raw material. However, in all cases the quality may be limited by the
      amount, composition and properties of the grain storage proteins. We describe how
      a combination of biochemical and molecular studies has led to an understanding of
      the molecular basis for breadmaking quality in wheat and feed quality in barley,
      and also provided genes encoding key proteins that determine quality. The control
      of expression of these genes has been studied in transgenic tobacco plants and by
      transient expression in cereal protoplasts, providing the basis for the
      production of transgenic cereals with improved quality characteristics.

PMID- 8142951
TI  - Expression of human lysozyme mRNA in the mammary gland of transgenic mice.
AB  - Owing to its inherent antimicrobial effect and positive charge, the expression of
      human lysozyme in bovine milk could be beneficial by altering the overall
      microbial level and the functional and physical properties of the milk. We have
      used transgenic mice as model systems to evaluate the expression of human
      lysozyme containing fusion gene constructs in the mammary gland. Expression of
      human lysozyme was targeted to the mammary gland by using the 5' promoter
      elements of either the bovine beta (line B mice) or alpha s1 (line H mice) casein
      genes coupled to the cDNA for human lysozyme. Expression of human lysozyme mRNA
      was not found in mammary tissue from any of line B mice. Tissues were analysed
      from six lines of H mice and two, H6 and H5, were found to express human lysozyme
      mRNA in the mammary gland at 42% and 116%, respectively, of the levels of the
      endogenous mouse whey acidic protein gene. At peak lactation, female mice
      homozygous for the H5 and H6 transgene have approximately twice the amount of
      mRNA encoding human lysozyme as hemizygous animals. Expression levels of human
      lysozyme mRNA in the mammary gland at time points representing late pregnancy,
      early, peak and late lactation corresponded to the profile of casein gene
      expression. Human lysozyme mRNA expression was not observed in transgenic males,
      virgin females or in the kidney, liver, spleen or brain of lactating females. A
      very low level of expression of human lysozyme mRNA was observed in the salivary
      gland of line H5.

PMID- 8142952
TI  - Tissue specific expression of an alpha-skeletal actin-lacZ fusion gene during
      development in transgenic mice.
AB  - Transgenic mice carrying a chimaeric transgene containing 730 bp of the 5'
      flanking sequences and the entire first intron of the rat alpha-skeletal actin
      gene fused to the lacZ reporter gene have been produced by microinjection. The
      lacZ reporter gene was used to verify the suitability of using the rat alpha
      actin promoter elements to target expression of genes of agricultural and
      therapeutic value exclusively to skeletal and heart muscle cells and fibres of
      transgenic mice. Expression of the transgene indicates a tightly regulated
      developmental and muscle specific control of the rat alpha-skeletal actin gene,
      making it a useful promoter for gene targeting to muscle tissues. The cells
      destined to form muscle tissues in these transgenic mice are readily visualized
      in intact embryos by staining for beta-galactosidase activity, making them a
      suitable animal model for studying the origin and development of skeletal and
      cardiac muscle tissues.

PMID- 8142953
TI  - [The hosts of Glossina fuscipes fuscipes Newstead, 1910 (Diptera: Glossinidae) in
      2 animal breeding zones in the Central African Republic].
AB  - From 1987 to 1993, a survey on the feeding behavior of Glossina fuscipes fuscipes
      was conducted in the Central African Republic. A total of 556 blood-meal samples
      was analyzed by ELISA. According to the results, the number of blood meals from
      cattle was rather low (12% on average). During the rainy season, this number
      increased significantly and varied according to the sampling area. Along the
      riverine forests, this amounted to 5%, while blood meals from wild ruminants
      amounted to 87%. In the neighborhood of watering-places, the number of cattle
      blood meals reached 9-22%. Reptiles were found to be important hosts (17-35%). In
      all cases, man presented a non-negligible host (4-14%), similar to suidae (2
      19%). The authors discuss the relevance of these results to risk of trypanosomes
      transmission.

PMID- 8142954
TI  - Coronavirus transmissible gastroenteritis virus-mediated induction of IFN alpha
      mRNA in porcine leukocytes requires prior synthesis of soluble proteins.
AB  - We studied the expression of interferon alpha (IFN alpha)-mRNA in porcine non
      adherent peripheral blood mononuclear cells (PBMC) after induction by the
      coronavirus transmissible gastroenteritis virus (TGEV). We found that protein
      synthesis inhibition by cycloheximide (CHX) blocked IFN alpha-mRNA expression,
      except when PBMC were preincubated with a conditioned medium as a potential
      source of cytokines. These data indicate that IFN alpha-mRNA induction by TGEV
      requires de novo synthesis of proteins. Moreover, they suggest that IFN alpha
      mRNA induction in porcine leukocytes by TGEV involves mechanisms identical to
      those described for the herpes simplex virus in humans. In addition, experiments
      performed with a TGEV mutant, dm 49-4, previously characterized for its low
      ability to induce IFN alpha, showed that addition of a conditioned medium could
      not normalize its IFN alpha-inducing ability. Therefore, the defect of the dm49-4
      mutant may be at the level of the final triggering signal to PBMC.

PMID- 8142955
TI  - [Homage to Paul Mornet].

PMID- 8142956
TI  - [Experimental infection of the mule duck by Eimeria mulardi sp. nov.: effects on
      body weight and modifications of different hematologic and biochemical
      parameters].
AB  - Eleven-day-old female Mule ducks (Cairina moschata x Anas platyrhynchos) were
      individually infected per os with a single inoculation containing 10(4), 10(5) or
      10(6) sporulated oocysts of E mulardi, or kept as uninfected controls. No
      mortality was observed. Growth rate was not modified at lower doses, but was
      reduced in the other 2 groups, with weight loss on d 7 post inoculation (PI).
      Blood was detected in feces by chemical characterization of hemoglobin as early
      as d 3 PI with the highest infecting dose, while oocyst excretion began on d 6 PI
      in all infected groups. With 10(5) and 10(6) oocysts, the authors observed a
      significant increase in sedimentation rate and a slight anemia. Total protein and
      lipid concentrations in the plasma decreased in the 3 infected groups. These
      results show the pathogenic effect of E mulardi in Mule duckling, with dose
      dependent changes. All parameters, except sedimentation rate, showed maximal
      variations during the acute phase of infection, between d 6 and d 9 PI, and
      returned to normal values early, in relation to the infecting dose, except that
      the weight remained lower than in the uninfected group at the final control (d 28
      Pl). These perturbations have been described in avian coccidiosis.

PMID- 8142957
TI  - Effects of glucagon on diuresis, renal plasma flow and glomerular filtration in
      sheep.
AB  - The effects of intravenous infusion of glucagon (100 ng.kg-1.min-1) on diuresis,
      renal plasma flow and glomerular filtration rate were studied in conscious sheep.
      Diuresis began to decrease upon initiation of glucagon infusion, down to 50% of
      its baseline value at the end of glucagon infusion. Glomerular filtration rate
      was also decreased by 75%. With regard to renal plasma flow, the decrease started
      at the beginning of glucagon infusion, but remained restricted. It was not
      possible, from these results, to explain the reduced diuresis by a decrease in
      renal plasma flow; the observed anti-diuretic effect could be the consequence of
      a modification of either the filtration coefficient or water tubular
      reabsorption.

PMID- 8142958
TI  - [Immunohistochemical localization in the intestine of swine of the cellular and
      humeral components of the immune response].
AB  - By immunohistochemistry, lymphocyte subsets of the swine gut were localized
      either in the epithelium or in the lamina propria. In addition, the distributions
      of class I and class II antigens were also characterized, using the streptavidin
      biotin-peroxidase complex as the revelator; the endogenous peroxidase activity
      was distinguished from the specific by cobalt chloride. The results show a
      compartmentalization in the distribution of lymphocytes: in the epithelium, all
      the cells were T lymphocytes, the majority of the CD8 phenotype; in contrast, in
      the lamina propria, T and B cells were represented in similar proportions: T
      cells were constituted of both CD4 and CD8 cells (with slightly more CD4 than CD8
      cells), while majority of B cells harboured the IgA isotype. Class I MHC was
      present on epithelium cells of both the villi and crypts. In contrast MHC class
      II was only present on epithelial cells of the villi. Both SC and IgA were
      localized in the epithelium cells of the crypt. Thus, this compartmentalization
      suggests the possibility of an immune response in the gut.

PMID- 8142959
TI  - Absence of protection against Eimeria ninakohlyakimovae after primo-infection
      with E ovinoidalis in new-born kids.
AB  - One group of kids (n = 23) was given 2 x 10(5) oocysts of Eimeria ovinoidalis
      (sheep coccidia) at birth; a second group (n = 23) was kept as an uninoculated
      control. Body weights, E ninakohlyakimovae oocyst output and serum coccidial
      antibody levels were monitored up to 77-102 d of age. No significant difference
      in any of these parameters was seen between the 2 groups, suggesting that no
      immune response to E ovinoidalis inoculation occurred. These results could be
      relevant to the absence of development of the endogenous stages of E ovinoidalis
      in kids and/or to the mode of inoculation (moderate and not repeated).

PMID- 8142960
TI  - Kinetic disposition of flunixin meglumine in the camel (Camelus dromedarius).
AB  - The kinetic disposition of flunixin meglumine was investigated in 5 camels after
      a single intravenous administration (1.1 mg/kg bwt). The plasma clearance was
      1.012 ml.min-1.kg-1, the steady-state volume of distribution 0.168 l/kg and the
      elimination half-life 2.51 h. The results are discussed and compared with those
      reported in cattle and horses.

PMID- 8142961
TI  - Pasteurella multocida: oropharyngeal carriage and antibody response in breeders.
AB  - The presence of Pasteurella multocida in the oropharynx of 58 pig, cattle or
      rabbit breeders whose livestock had suffered from pasteurellosis was investigated
      using a selective medium. Blood samples for serological studies were collected at
      the same moment. Nineteen breeders were found to host one P multocida subsp
      multocida strain. Oropharyngeal carriage of P multocida was found to be more
      frequent in pig breeders (42% of individuals) than in cattle (10%) or rabbit (0%)
      breeders. Genomic polymorphism among 10 D2 strains was found by restriction
      endonuclease analysis using pulsed-field gel electrophoresis (REA-PFGE).
      Antibodies to P multocida were found in the sera of 32 of these 58 breeders,
      whereas only 2 of the 70 controls had antibodies. These results, recorded from
      healthy individuals, show that P multocida, acting as an opportunistic bacterium,
      may be responsible for occupational diseases. Nevertheless, the strong prevalence
      of specific antibodies makes the presence of antibodies in the sera of these
      breeders an insufficient indication of a current patent infection.

PMID- 8142962
TI  - Managing early HIV infection. Agency for Health Care Policy and Research.
AB  - This Quick Reference Guide for Clinicians contains highlights from the Clinical
      Practice Guideline on Evaluation and Management of Early HIV Infection, which was
      developed by a private-sector panel of health care providers and consumers.
      Selected aspects of evaluating and managing patients, both adults and children,
      who are in the early stages of human immunodeficiency virus infection are
      presented. Topics covered include disclosure of HIV status, monitoring of CD4
      lymphocyte counts, prevention of Pneumocystis carinii pneumonia and infection
      with Mycobacterium tuberculosis, initiation of antiretroviral therapy, treatment
      of syphilis, eye and oral care, performance of Papanicolaou smears, diagnosis of
      HIV infection in infants and children, preventive therapy for PCP and assessment
      of neurologic problems in HIV-infected children, pregnancy counseling, and
      development of a comprehensive case management system. Algorithms are included
      that show the sequence of events related to evaluating and managing early HIV
      infection in adults and children, as well as drug dosing tables for
      antiretroviral, PCP, and M. tuberculosis therapies.

PMID- 8142963
TI  - [Experience with the surgical management of fractures of the tibial head].
AB  - In the Department of Traumatology of the "Kaposi Mor" County Hospital 213
      patients with the fracture of the proximal end of the tibia were treated during
      10 years (1980 + 89). 165 operated cases are analysed, 120 of them could be
      controlled 1.5-9 years after the operation. The importance of the reconstruction
      of the articular surfaces is stressed and attention is called to the increased
      possibility of infection in these operations.

PMID- 8142964
TI  - [A newly developed cementless elbow joint prosthesis].
AB  - Authors describe briefly the history of the development of elbow arthroplasty.
      They report on their experiences with the silicone, cementless, unconstrained
      elbow prosthesis developed by them and implanted in 23 cases during 3 years. The
      prosthesis is described, the operative indication and the problems of the
      operative technique are reviewed. On the basis of their results and the low
      number of complications this method of operation is suggested first of all for
      the successful treatment of elbows with rheumatoid arthritis.

PMID- 8142965
TI  - [Scintigraphy of the carpal joint].
AB  - Author performed scintigraphic examinations for the exclusion of navicular
      fracture, to follow the consolidation of the pseudarthrosis of the navicular bone
      and to demonstrate the osteoarthritis of the wrist joint. He states that bone
      scintigraphy is a help in the differential diagnosis of the fracture of the
      navicular. Conclusion may be drawn concerning the circulatory state of the bone.
      The consolidation of the pseudoarthrosis may be followed and the severity of the
      osteoarthritis of the carpal joint can be determined.

PMID- 8142966
TI  - [Synovitis and bone changes induced by silicone prosthesis].
AB  - Authors report on the clinico-pathological analysis of cases of silicon
      granuloma, developed 5-15 years after the insertion of the prosthesis. It is
      thought on the basis of histological and electron microscopic examinations that
      the process of granulation already started, is augmented by the granules, newly
      arising from the attrition. The silicon granuloma causes not only the damage of
      the synovia but the destruction of the surrounding soft parts and bones too.

PMID- 8142967
TI  - [Diagnostic procedures in cases of wrist pain following distortion of the wrist].
AB  - Behind the diagnosis of "distorsio carpi" frequently ligamental injuries with
      severe functional damage of the carpal joint are hidden. To clear these is, in a
      significant part of the cases, also in the outpatient department possible if both
      the clinical (physical) and radiological examinations are carried out with
      adequate accuracy. Author deals with the "algorithm", summarizing the sequence of
      these examinations. If, in major complaints, it was not possible to make a
      diagnosis, an arthroscopy of the carpal joint is suggested.

PMID- 8142968
TI  - [Results of the treatment of osteoblastomas].
AB  - Until now 19 patients were treated for osteoblastoma in our University
      Department. Operation was performed in every case and recurrence was found in one
      patient. The clinical-pathological characteristics of the benign, latent, active
      and aggressive osteoblastomas are discussed. In benign active process excision,
      in benign aggressive tumors, depending from the localization, resection en bloc
      is suggested. In cases localized near to the joint, weighing the damage of
      function in consequence of a possible resection and the increased risk too, a
      thorough excision is proposed completed with local adjuvant treatment and
      frequent control of the patient.

PMID- 8142969
TI  - [Functional treatment of humeral diaphyseal fractures using a Hungarian
      manufactured brace].
AB  - Authors suggest, in their paper, a new method in this country, the so called
      brace treatment for the functional treatment of the diaphyseal fractures of the
      humerus. A 2-4 fifth of the diaphyseal fractures of the humerus can be treated in
      the majority with this method. An other novelty of this treatment is the humerus
      brace developed and manufactured in Hungary. This fracture treatment has
      unequivocal advantages both for the health service and the patient for its
      shorter duration of healing and treatment.

PMID- 8142970
TI  - [Surgical treatment of hip dislocations in children and damages caused by
      conservative treatment methods].
AB  - For the major requirements of the operative technique and other special problems
      of operation it is reasonable to discuss among the questions of the reduction of
      CHD the reoperations and the reconstructive surgery of hips, badly damaged by the
      conservative treatment, separately. We have analysed the results of 19 own cases
      with an average follow up of 6.3 years (3-12 years). The average age of the
      patients was 4.8 years. In 7 patients only conservative treatment was carried out
      previously, the others were also operated. The Roentgenogram revealed severe
      ischaemic necrosis in 10 hips. The dislocation could be reduced in every case, to
      the reduction however it was obligatory to add femoral osteotomy and correction
      of the acetabulum. The later operation was performed frequently in the second
      sitting. As a direct result of the operation a state, corresponding to the II.
      degree of Severin's radiological classification was always reached, in cases of
      severe ischaemic necrosis however the result later grew worse and at the follow
      up it corresponded only to the degrees III. and IV. (mediocre, poor). Thus the
      circulatory damage, suffered during the early treatment determined the late
      results. This was the reason that the result of the follow up examinations were
      better in patients in whom early surgery was performed than in patients with
      forced conservative treatment. The results summarized fall far behind the results
      of the group with primary surgery of the CHD. Without the operations described
      these patients would live as limping cripples, with these operations however we
      have improved their state significantly for the time until TEP can be performed.

PMID- 8142971
TI  - [Substitution of the external malleolar ligament with a periosteal flap].
AB  - Substitution of lateral malleolar ligament with a periosteal flap Authors
      describe their operative procedure for chronic instability of the lateral
      malleolar ligament: substitution of this ligament with a periosteal flap. This
      operation is suitable, according to follow up examinations, both in isolated
      talofibular and talofibular-calcaneofibular ligamental deficiencies, for the
      stable restitution with good function of the talorural joint. The advantage of
      the operation is that less burden is imposed on the patient, the technique is
      relatively simple, and the need of instruments is minimal. Control examinations
      have shown very good or good results in the majority of 16-49 years old operated
      patients.

PMID- 8142972
TI  - [One-year follow-up experience in the rehabilitation of patients with femoral
      neck fractures].
AB  - Authors have followed 754 patients with hip fracture and have found that about 60
      per cent of them are alive after one year; their functional state further
      improved between 4 months and 1 year, it cannot be however considered as
      satisfactory even after one year. Analysing the operations performed in femoral
      neck and trochanteric fractures it should be stated that the operative
      indications are generally adequate and the conditions of further improvement are
      defined. More significant improvement of the lasting results can be expected from
      a well organized rehabilitation.

PMID- 8142973
TI  - [Symmetrical bone formation in the Achilles tendon].
AB  - Author reports on a case of ectopic bone formation in the Achilles-tendons and
      reviews the literature. The pathologic change was caused probably by the chronic
      mechanical irritation suffered during the conservative treatment of the club
      feet. The continuity of the ossified mass was interrupted similarly to a
      fracture; the function was restored after an "osteosynthesis".

PMID- 8142974
TI  - [Rehabilitation of knee joint instability caused by pseudarthrosis of the lateral
      femoral condyle].
AB  - Authors report on the successful operative treatment, 15 years after the
      development of a pseudarthrosis, following the fracture of the lateral femoral
      condyle and causing knee instability. In this case the refreshing of the
      avascular pseudarthrosis gap reduction and screw osteosynthesis were performed.
      The basic principles of the distribution and treatment of pseudarthrosis are
      reviewed. Attention is called to the importance of exact reduction and stable
      fixation and to the fact that reconstruction can be carried out even long after
      the injury.

PMID- 8142975
TI  - [Osteochondroma causing scapula alata].

PMID- 8142976
TI  - [Cases of traumatic (Putscher) retinopathy associated with severe facial
      injuries].
AB  - The author describes two men who suffered traffic accident that caused severe
      malar lesion, followed by unilater Purtscher's retinopathy. The prognosis of this
      rare retinopathy is good if the papillomacular arterial branches are not or only
      partially occluded, and the capillar perfusion is intact. He explains the
      hypothetic pathomechanism of the traumatic process, the therapeutic possibilities
      and their limitations. Last, he calls the attention of traumatologists to the
      possibility of vision-loss without any direct ocular lesions.

PMID- 8142977
TI  - [Successful operation of a stab-wound in the inferior vena cava].
AB  - Author describes the case of a 26 years old injured male patient in whom a
      permeating injury of the inferior vena cava was caused by a knife stab. The
      patient was treated successfully. The localization and the possibilities of
      treatment are described. To publish this case was found worth while as in the
      Hungarian literature only one similar case was found yet.

PMID- 8142978
TI  - Psychosocial impact of persistent trophoblastic disease.
AB  - The female identity of women who suffer from hydatidiform mole developing into
      persistent trophoblastic disease is threatened in two ways. The reproductive
      failure is shortly followed by a disease originating in the uterus requiring
      chemotherapy. Although somatic treatment results are excellent, the psychological
      effects may be severe and protracted. We conducted a study of 22 women who were
      between 6 months and 5 years after the end of successful treatment. It appeared
      that 19 women suffered from psychological sequelae. The three oldest women of the
      study group, 50 years or older, belonged to the group of women demonstrating
      signs of prolonged psychological effects.

PMID- 8142979
TI  - Psychosocial factors and intrauterine fetal growth: a prospective study.
AB  - This study focused on the possible role of psychosocial factors on intrauterine
      fetal growth. Pregnant women (n = 236) completed questionnaires on daily
      stressors and psychosomatic symptoms three times during pregnancy; in the 11-12th
      week, the 23-24th week and the 35-36th week. In addition, information was
      obtained on the quality of the marital relationship, social support, social
      class, physical work load, weight of the biological parents and life-style
      variables (including smoking, alcohol and coffee consumption). Birth weight
      corrected for gestational age, sex and parity was utilized as an index of
      intrauterine fetal growth. This dependent measure did not appear to be affected
      by exposure to daily stressors or disturbed maternal well-being on any of the
      measuring points. Smoking appeared to be the best predictor of fetal growth,
      together with maternal weight and the family's socioeconomic status. These
      variables accounted for 10.6% of the variance. It is postulated that the absence
      of a relationship between stressors and fetal development may be due to the
      buffering effects of adequate emotional support provided by the partners and the
      further social network.

PMID- 8142980
TI  - Menstrual cycle hormonal profiles of women with and without premenstrual
      syndrome.
AB  - This paper compares the urinary hormone profiles of estrogen and pregnanediol in
      women with documented premenstrual syndrome (PMS) (n = 65) and asymptomatic
      volunteers (n = 18). Daily 24-h urine samples were collected for an entire
      menstrual cycle. Subject groups did not differ significantly in menses length or
      in the day of the preovulatory estrogen peak. Cycle length was significantly
      shorter for the volunteers (p < 0.05). The day of the pregnanediol peak occurred
      significantly later for the PMS patient group than for the asymptomatic
      volunteers (p < 0.05). Split plot analysis of variance showed no significant
      differences overall between subject groups for levels of urinary estrogen or
      pregnanediol. This study did not find evidence of progesterone deficiency amongst
      sufferers of the premenstrual syndrome.

PMID- 8142981
TI  - Serum androgens and psychopathology in hirsute women.
AB  - Twenty consecutive women referred for evaluation and treatment of idiopathic
      hirsutism were evaluated with regard to levels of serum androgens, degree of
      hirsutism, nature and prevalence of psychological symptoms, and mood and affects.
      Androgens measured were total testosterone, free testosterone, biologically
      active testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and
      androstenedione. Psychological symptoms were quantified via the Derogatis Symptom
      Inventory, and mood and affects were measured by the Affects Balance Scale.
      Results revealed very significant correlations between unbound fractions of
      testosterone (i.e. free and biologically active testosterone) and both symptom
      and mood measures of depression (r = 0.60; p < 0.01). Significant inverse
      correlations were also observed between unbound fractions of testosterone and
      positive affects measures (e.g. 'contentment' r = -0.51; p < 0.05). Correlations
      between total testosterone and psychological variables were non-significant in
      all instances. Measures of degree of hirsutism correlated approximately zero (o)
      with psychological symptom and mood measures in this sample. When psychiatric
      'caseness' criteria were applied to the cohort, seven of the 20 women (35%) were
      found to be positive. Results are interpreted to suggest that depression among
      hirsute women appears more likely to have its basis in a deranged neuroendocrine
      mechanism than in psychosocial causes.

PMID- 8142982
TI  - Elective ovarian removal and estrogen replacement therapy--effects on sexual
      life, psychological well-being and androgen status.
AB  - Conflicting data have been reported on the psychosexual impact of hysterectomy
      combined with bilateral oophorectomy. Three age-matched, hysterectomized groups
      of women were investigated: Group A (n = 33): oophorectomized, not receiving
      estrogen replacement therapy (ERT); Group B (n = 33): oophorectomized, receiving
      ERT; and Group C (n = 35): ovaries preserved and not receiving ERT. The McCoy
      Sexual Rating Scale and the Psychological General Well-Being Index as well as a
      semi-structured interview were used to assess postoperative experience with
      respect to libido, vaginal lubrication, ability of getting pleasure from
      intercourse, and ability to achieve orgasm. Serum concentrations of total and
      free testosterone, insulin-like growth factor I (IGF-I), sex hormone binding
      globulin, dehydroepiandrosterone sulfate and 4-androstene-3,17-dione were
      determined. In oophorectomized women sexual life was impaired as compared to
      those with intact ovaries and these women complained about less pleasure from
      coitus, impaired libido and lubrication. Regardless of whether estrogens were
      administered or not a similar pattern was found, indicating that estrogens are of
      little value in treating these specific sexual dysfunctions. Oophorectomized
      women receiving ERT reported less anxiety and depression and more well-being
      similar to women whose ovaries had been preserved. No correlation was found
      between psychosexual variables and biochemical androgen markers. However, the IGF
      I levels were strongly correlated to sexual activity and responsiveness.

PMID- 8142983
TI  - The tyramine test is not a marker for postnatal depression: early postpartum
      euphoria may be.
AB  - Abnormally low tyramine test values are known to be markers for vulnerability to
      unipolar, but not bipolar, endogenous depression. In the present study, 37 women
      with recent postnatal depression (25 major, 12 minor) and 22 puerperal controls
      with no depressive disorder, all assessed by Schedule for Affective Disorder and
      Schizophrenia (SADS-L) interview, together with 17 other controls, underwent the
      test. No significant differences in tyramine sulfate output were demonstrated
      between the different groups. Those subjects with endogenous features according
      to Newcastle score (n = 7) or Research Diagnostic Criteria (RDC) (n = 6) also had
      normal output. Thus, the tyramine test does not appear to be a useful marker for
      vulnerability to postnatal depression. Over half the subjects recalled that their
      postnatal depression had started in the first 2 weeks postpartum. Of the total of
      62 postpartum subjects interviewed with the SADS-L, ten recalled a period of
      euphoria in the first postpartum week, which met RDC for hypomania and eight of
      them went on to become depressed postnatally. An additional patient from the
      total group was hospitalized with mania.

PMID- 8142984
TI  - Advances in the practice of assisted reproduction.

PMID- 8142985
TI  - Quality of parenting in families created by the new reproductive technologies: a
      brief report of preliminary findings.
AB  - The creation of families by means of the new reproductive technologies has raised
      important questions about the consequences for parent-child relationships,
      particularly where gamete donation has been used to conceive the child.
      Preliminary findings are presented of a study of the quality of parenting in
      families created as a result of the two most widely used reproductive
      technologies, in vitro fertilization and donor insemination, in comparison with a
      control group of families with a naturally conceived child and a control group of
      adoptive families. The quality of parenting was assessed using a standardized
      interview with the mother, and mothers and fathers completed questionnaire
      measures of stress associated with parenting. The results showed that the quality
      of parenting in families with a child conceived by assisted conception is
      superior to that shown by families with a naturally conceived child. The findings
      are discussed in terms of their implications for understanding the role of
      genetic ties in parent-child relationships.

PMID- 8142986
TI  - Children from anonymous donors: an inquiry into homosexual and heterosexual
      parents' attitudes.
AB  - This study compared two groups of homosexual and heterosexual parents with
      respect to their attitudes towards the donor-origin of their children. All
      couples had applied at the Fertility Clinic for artificial insemination with
      anonymous donor sperm (AID). Both groups had used anonymous donors in order to
      conceive. However, the sexual orientation of the parents and the presence or
      absence of a social father was different in the two groups. By comparing such
      different families it was hoped to obtain insight into those factors which
      influence parents' attitudes concerning donor insemination. Twenty-five lesbian
      and 25 heterosexual parents were interviewed. The open-ended questionnaires
      solicited information on the following issues: attitudes towards
      secrecy/disclosure of the use of a donor, views on anonymity/identity
      registration of the donor, parents' cognitive and emotional representation of the
      donor. Response rates differed between the groups: all homosexual parents
      consented to the interview and 44% of the heterosexual parents did so. Parents'
      attitudes depended on several variables. The different family structures were
      related to different motivations for AID treatment. For heterosexual couples, the
      use of a donor offered them the opportunity to become a 'normal family'. For
      homosexual couples, creating a two-mother family unit meant going one step
      further in 'being different'. Attitudes towards the use of a donor were
      consequently different: heterosexual couples chose secrecy and donor anonymity.
      Homosexual parents intended to inform their children. Of these homosexual
      parents, 40% would prefer the identity of the donor to be registered. This
      evolution towards removal of the anonymity seemed to be encouraged by the
      openness surrounding the use of a donor itself. In both groups it remained
      difficult to reduce the donor to an anonymous sperm cell, fantasies and questions
      about the donor continued to exist over the years.

PMID- 8142987
TI  - Screening in or out of the new reproductive options: who decides and why.
AB  - A lively controversy exists among infertility specialists about the value and
      necessity of screening candidates for inclusion into infertility programs.
      Advocates of screening argue that there is both a child advocacy and community
      welfare responsibility to evaluate prospective candidates (and donors) for the
      new assisted reproductive techniques. Opponents of screening argue that screening
      is costly and superfluous, since the majority of applicants are highly motivated
      and well-adjusted individuals who have the 'right' to pursue parenthood, if they
      choose. A pilot survey was undertaken to determine whether infertility programs
      currently have explicit policies regarding suspension or refusal of treatment on
      psychological grounds and to determine what would (or should) constitute grounds
      for denial of infertility treatment. A Treatment Refusal Questionnaire was mailed
      to all members of the Psychological Special Interest Group of the American
      Fertility Society. Forty-two responded (response rate of 47%). Results revealed
      that the majority of respondents did not have a formal policy regarding
      suspension or refusal of treatment, although they did have informal criteria.
      Four criteria were significantly endorsed as constituting 'red flags' for
      treatment rejection: substance abuse, physical abuse, severe marital strife, and
      coercion of one spouse by another. Furthermore, treatment decisions were modified
      by the type of intervention sought, so that for example, more stringent criteria
      were operative if clients sought ovum donation than if they sought ovulation
      induction. These and other findings are presented and discussed.

PMID- 8142988
TI  - The psychological impact of infertility: a comparison with patients with other
      medical conditions.
AB  - To compare the psychological symptoms of infertile women with patients with other
      chronic medical conditions, subjects completed the Symptom Checklist-90 (Revised)
      (SCL-90R), a standardized, validated and widely used psychological questionnaire,
      prior to enrolling in a group behavioral treatment program. All subjects were
      female and the totals in each program were as follows: 149 with infertility, 136
      with chronic pain, 22 undergoing cardiac rehabilitation, 93 with cancer, 77 with
      hypertension, and 11 with human immunodeficiency virus (HIV)-positive status. The
      infertile women had global symptom scores equivalent to the cancer, cardiac
      rehabilitation and hypertension patients, but lower scores than the chronic pain
      and HIV-positive patients (p < 0.0001 and p < 0.02 respectively). The anxiety and
      depression scores of the infertile women were significantly lower than chronic
      pain patients but not statistically different from the other groups. The results
      suggest that the psychological symptoms associated with infertility are similar
      to those associated with other serious medical conditions. Therefore, standard
      psychosocial interventions for serious medical illness should also be applied in
      infertility treatment.

PMID- 8142989
TI  - A follow-up study of 'successful' IVF/GIFT couples: social-emotional well-being
      and adjustment to parenthood.
AB  - Twenty couples who conceived their babies by in vitro fertilization/gamete
      intrafallopian transfer (IVF/GIFT) were seen between 15 and 27 months
      postdelivery in order to evaluate social-emotional well-being and parental
      functioning. Emotional health and marital adjustment were assessed by standard
      questionnaires and compared with general population norms. Questionnaires
      measuring quality of life, parents' feelings about their babies and child-rearing
      attitudes were also administered. Scores from these were compared with those
      obtained from a group of parents who had conceived without medical assistance.
      Results indicated that IVF/GIFT parents were undifferentiated from the general
      population with respect to emotional health and marital adjustment. Also,
      relative to non-IVF parents, they gave higher positive ratings for their feelings
      about their babies and for one aspect of quality of life (feelings of freedom).
      Parenting attitudes for the two groups differed in only one respect, IVF/GIFT
      parents reported being more overprotective.

PMID- 8142990
TI  - Long-term infertile couples: a study of their well-being.
AB  - The objective of the study was to investigate long-term infertile couples in
      regard to their well-being. The design of the study consisted of a structured
      questionnaire. Husband and wife answered a written questionnaire each in a
      different place in their home. Wives and husbands of 108 childless couples with a
      long-term infertility participated. Seven dimensions of (negative) well-being
      were measured: depression, anxiety, hostility, health complaints, guilt/blame,
      self-esteem and sexuality. Results showed that sexual behavior was (still) often
      ruled by the constraints of procreation. Also a third of the women reported as a
      consequence of infertility a low self-esteem concerning their womanhood.
      Infertile women were more anxious, more depressed, displayed more hostility and
      reported more health complaints. There was no similar difference between long
      term infertile men and men in general. In conclusion long-term infertile women
      showed a significantly-lower level of well-being compared with women in general.
      A third of the infertile women and a fifth of the infertile men had serious well
      being problems. This group can be considered as needing emotional help and
      counselling in learning to live with their childlessness.

PMID- 8142991
TI  - Priorities and research strategy in health economics for the 1990s.

PMID- 8142992
TI  - The costs and effects of open versus laparoscopic cholecystectomies.
AB  - The costs and effects of open versus laparoscopic cholecystectomies are compared,
      from the point of view of hospitals and patients, for a consecutive series of 47
      patients undergoing a cholecystectomy in the University Hospital Gasthuisberg, in
      Belgium. For the patients the laparoscopic technique is superior, since effects
      are better and direct costs are lower than for the open technique. From a
      financial viewpoint, hospitals have to weigh the higher costs of the laparoscopic
      equipment against the lower variable costs due to the shorter postoperative
      length of stay. Total hospital costs would be lower in case all cholecystectomies
      were performed with the laparoscopic rather than with the open technique if at
      least 140 cholecystectomies are done annually with the electrocautery technique,
      or 300 procedures with laser. However, more recent data reveal that the operating
      time reduces with the number of laparoscopic procedures (learning effects),
      implying that the laparoscopic electrocautery procedure would already be the
      cheaper alternative if more than 70 cholecystectomies are done annually, if
      disposables are used (or if 50 procedures are done with re-usables). It can be
      concluded that, once sufficient experience with laparoscopy has been achieved,
      most hospitals could realise cost savings by switching, as much as is medically
      justified, to laparoscopic procedures. This will also hold for hospitals
      performing few cholecystectomies, as long as re-usables and electrocautery are
      used.

PMID- 8142994
TI  - Monitoring health in Sweden: on the rationale for working environment
      regulations.
AB  - The quality of the working environment affects the health status of a population.
      In the absence of government intervention this quality would be determined by
      market forces, but the market outcome is generally not accepted. Instead public
      policy attempts to carefully monitor the level of occupational hazards, which are
      invariably subject to regulation in industrialized countries. However, this study
      demonstrates that the welfare implications of this monitoring of health are not
      self-evident. In the presence of a tax on labour and, for example, a tax-financed
      social insurance system, it is shown that market forces may lead either to
      excessive or to sub-optimal investments in injury prevention. Both private and
      (local) public safety goods are considered.

PMID- 8142995
TI  - Is malaria control a priority? Evidence from Nepal.
AB  - The research reported here assessed the value of malaria control through a cost
      effectiveness study of the vertically-organized malaria control programme in
      Nepal. It presents a methodological framework for analysing cost-effectiveness
      which includes resource-saving consequences as well as health consequences. The
      methods used to collect data on control costs, cases and deaths prevented,
      treatment costs averted and production gains are described and the assumptions
      required by the analysis are made explicit. A variety of cost-effectiveness
      ratios are calculated, sensitivity analysis applied and the policy implications
      of the results considered. The results from Nepal are compared to estimates for
      parasitic disease and other health programmes in other countries: it is concluded
      that the Nepalese programme appears no less cost-effective than many other health
      interventions. It can also be justified by reference to the population groups
      benefiting from malaria control.

PMID- 8142993
TI  - Reduced list costings: examination of an informed short cut in mental health
      research.
AB  - The demands for cost information in health services are many and various but the
      supply of such information is less than might be expected and is compounded by
      the expense of undertaking costs research. This paper examines a short cut to
      mental health research which, if certain rules and conventions are obeyed, can
      still produce valid costs data. By distilling evidence from previous research a
      reduced list of services is identified which accounts for the greater part of the
      total costs of care packages. By concentrating on these key services, 94 per cent
      of the total costs of care were predicted for discharged long-stay patients and
      no less than 91 per cent for people supported by community psychiatric nurses.
      The results suggest that this reduced list method can work well where the aim is
      to obtain broad orders of magnitude for the costs of care. By reducing the
      resources required for research, the approach could expand the current costs
      information base and move towards meeting the pressing practice demands for costs
      data.

PMID- 8142996
TI  - Measuring utility values for QALYs: two methodological issues.
AB  - Two methodological concerns in utility estimation, the development of health
      state descriptions (scenarios) and the interpretation of interval scale anchor
      points, are examined in the context of disease-specific cost utility analyses
      (CUA). It is contended that results in CUA can be fundamentally biased by: (i)
      how the information presented in a scenario is generated; and (ii) the
      researcher's 'definition' of anchor points, when these are used as bounds to the
      interval scale. A number of recommendations are made, in particular for a more
      explicit reporting of these issues in CUA, to facilitate greater consistency in
      the application of utility measurement techniques.

PMID- 8142997
TI  - The contingent valuation method--appraising the appraisers.
AB  - Morrison & Gyldmark (MG) in a recent issue of health economics reviewed the use
      of the contingent valuation (CV) method of measuring willingness to pay in the
      health area. Although it is useful to examine the appropriate role of the CV
      method in the health care field, the appraisal by MG has a number of limitations
      which are pointed out in this paper. These relate to some inaccuracies in the
      review of the literature, the limited nature of the criteria proposed by MG to
      evaluate CV studies, and finally I argue that the comparison between CV, QALYs,
      and HYEs is premature and confuses rather than clarifies the debate.

PMID- 8142998
TI  - Appraising the use of contingent valuation: a note in response.
AB  - This paper reviews the guidelines and recommendations propounded by Morrison and
      Gyldmark in relation to the use of contingent valuation (CV) to value health
      states. The issues raised are: that QALYs may not be sufficiently sensitive to
      changes in health thus requiring the use of CV formulation; the questionable
      practice of reinterpreting monetary values; and the possibility of income bias.
      It is concluded that further empirical research, at least, is needed to verify
      whether this approach should be rejected in favour of quality adjusted life years
      (QALYs) or healthy year equivalents (HYEs).

PMID- 8142999
TI  - Cost-effectiveness of endoscopic surgery.
AB  - Endoscopic surgery is a rapidly defusing treatment approach subject to continual
      technological advance. It offers great potential for economic benefits as well as
      health gains, but as shown in the article in this issue by Kesteloot and
      Penninckx, the relative cost of open versus endoscopic surgery is a quite complex
      issue. The main factors influencing the costs and effectiveness of endoscopic
      surgery are reviewed and the need for more and better evaluation studies
      highlighted.

PMID- 8143000
TI  - Stress and the residency program director.
AB  - A survey of pediatric program directors was performed to identify stressors on
      pediatric residents as perceived by the directors and to ascertain the
      relationship of stress experienced by house staff and faculty. Major stressors
      for pediatric residents were acuity/complexity of patient diseases and financial
      concerns. Major stressors for program directors were administrative duties.
      Although nearly three fourths of the program directors had completed a
      fellowship, only one half were on the tenured track. The majority of program
      directors believed that as resident working hours and stress decreased, faculty
      workload and stress increased. Stress experienced by faculty appears to require
      further investigation and remediation.

PMID- 8143001
TI  - Cow's milk is a good food for some and a poor choice for others: eliminating the
      hyperbole.

PMID- 8143002
TI  - Your child is poisoned: reflections on the new lead guidelines.

PMID- 8143003
TI  - Counseling parents about guns in the home.

PMID- 8143004
TI  - The changing of the guard.

PMID- 8143005
TI  - Sexual abuse, adolescent pregnancy, and child abuse. A developmental approach to
      an intergenerational cycle.
AB  - OBJECTIVE: To elucidate the relationship between childhood sexual abuse and
      adolescent pregnancy. DATA SOURCE: Articles published in English during the past
      two decades and pertaining to the sequelae of childhood sexual abuse or the
      antecedents of adolescent pregnancy. STUDY SELECTION: Studies that did not
      contain data pertinent to the relationship between childhood sexual abuse and
      adolescent pregnancy were excluded. RESULTS: Studies suggest that former victims
      of childhood sexual abuse may be at increased risk for conception during
      adolescence and that adolescent pregnancies that are antedated by childhood
      sexual abuse are often only one manifestation of socially deviant behavior.
      CONCLUSIONS: Experiences associated with childhood sexual abuse may affect the
      incidence and the outcome of adolescent childbearing. Identification and
      treatment of previously abused adolescent prenatal patients may break this
      vicious intergenerational cycle of violence.

PMID- 8143006
TI  - Diet therapy for hypercholesterolemia in children and adolescents. A follow-up.
AB  - OBJECTIVE: To determine the effectiveness and compliance of dietary restriction
      in a group of children and adolescents with hypercholesterolemia. RESEARCH
      DESIGN: Prospective clinical trial. SETTING: Pediatric hospital in Madrid, Spain.
      PARTICIPANTS: Four hundred fifty-one children and adolescents of both sexes aged
      2 to 18 years diagnosed as having hypercholesterolemia and treated with dietary
      restriction (American Heart Association Step-One and Step-Two Diets). The follow
      up period ranged from 6 months to 2 years and was performed by one pediatrician.
      RESULTS: Total cholesterol, low-density lipoprotein cholesterol, and
      apolipoprotein B-100 levels as well as the low-density lipoprotein
      cholesterol/high-density lipoprotein cholesterol ratio decreased significantly (P
      < .01) from the first month of dietary restriction, whereas the high-density
      lipoprotein cholesterol level increased (P < .01). The apolipoprotein A-I level
      increased significantly (P < .01) only after 6 months of diet therapy. After 12
      months of follow-up, 30.7% (58/189) of patients did not follow the diet strictly.
      In this group, significantly higher levels of total cholesterol, low-density
      lipoprotein cholesterol, and apolipoprotein B-100 were found. CONCLUSIONS: Diet
      therapy is effective in the treatment of hypercholesterolemia in children and
      adolescents. Dietary restriction has a beneficial effect not only on total
      cholesterol and low-density lipoprotein cholesterol levels but also on
      apolipoprotein A-I and B-100 levels.

PMID- 8143007
TI  - Imaging evaluation of artificial nipples during bottle feeding.
AB  - OBJECTIVES: To determine whether real-time ultrasonography can be used to
      directly visualize artificial nipples in vivo while an infant is sucking, to
      compare deformation differences of the artificial nipple with the human nipple
      during sucking, and to compare the suck mechanism used by the infant with four
      types of artificial nipples. DESIGN: Nonrandomized clinical study with a control
      group. SETTING: University-affiliated teaching hospital in Iowa City, Iowa.
      PARTICIPANTS: A volunteer sample of 35 healthy infants 6 to 12 weeks of age.
      INTERVENTION: None. MEASUREMENTS/MAIN RESULTS: Images produced by real-time
      ultrasound of infants during sucking using artificial nipples were measured to
      determine the percentage lengthening, the percentage lateral compression, and the
      percentage flattening of nipples. These results were compared with data obtained
      from studies using breast-fed infants. None of the artificial nipples lengthened
      like the human nipple. One artificial nipple was significantly more compressible
      than the human nipple and the remaining three artificial nipples. CONCLUSION:
      Real-time ultrasonography can be used to visualize artificial nipples in vivo
      during sucking.

PMID- 8143008
TI  - Midgut volvulus. An ever-present threat.
AB  - OBJECTIVE: To identify risk factors for midgut volvulus (MGV) and to seek clues
      to early diagnosis of MGV in children with malrotation. DESIGN: Retrospective
      patient series. SETTING: Academic medical center. PATIENTS: Sixty-eight
      consecutive children who had a Ladd operation performed between January 1970 and
      December 1991. Excluded were three patients whose records were unavailable and
      patients who had a Ladd operation during the course of repair of an abdominal
      wall defect or congenital diaphragmatic hernia. RESULTS: Forty of 68 patients had
      MGV at operation. There was an inverse correlation between age at onset of
      symptoms and the probability of MGV: 85% (29/34) of patients less than 1 month of
      age had MGV compared with 43% (10/23) of older children. Patients who had
      symptoms for less than 4 days were more likely to have MGV (88%; 30/34) than
      patients who had more chronic symptoms (43%; 10/23). Bilious (green) vomiting was
      more highly associated with MGV (80%; 35/44) than nonbilious vomiting (38%; 3/8)
      or pain (50%; 6/12). Roentgenograms of the upper gastrointestinal tract were very
      accurate for the diagnosis of malrotation but frequently failed to identify MGV
      (sensitivity, 54%; 13/24). Despite the high proportion of MGV, only three
      patients had gangrenous bowel. Of these three patients, one died and two have
      short-gut syndrome. CONCLUSION: Neonates with a short history of bilious vomiting
      are most likely to have MGV-complicating malrotation, but older children who have
      chronic intermittent symptoms are also at risk. Since there is no way to predict
      which patients will develop catastrophic bowel necrosis, early diagnosis and
      operation are necessary to prevent mortality and short-gut syndrome.

PMID- 8143009
TI  - Epiglottitis in children, 1979 through 1992. Effects of Haemophilus influenzae
      type b immunization.
AB  - OBJECTIVE: To examine secular trends in the epidemiology, bacteriology, and
      clinical presentation of acute epiglottitis in children in the years surrounding
      the introduction of vaccine against Haemophilus influenzae type b. DESIGN:
      Retrospective chart review of patient series. SETTING: Large, urban, tertiary
      care pediatric hospital. SUBJECTS: One hundred forty-two children with
      epiglottitis admitted during a 14-year period (1979 through 1992). MAIN RESULTS:
      The average annual incidence of epiglottitis declined from 10.9 per 10,000
      admissions before 1990 to 1.8 per 10,000 admissions from 1990 through 1992. The
      median age increased from 35.5 months in the earlier period to 80.5 months (P =
      .007). Overall, H influenzae type b was identified as the causative organism in
      76% of patients, but in only 25% of the cases since 1990 (P = .004). Of the eight
      cases from 1990 through 1992, three had group A beta-hemolytic streptococcus
      isolated from a surface culture of the epiglottis; three other cases of group A
      beta-hemolytic streptococcus were identified earlier. These patients were
      significantly older than those with H influenzae type b disease (117.5 vs 35
      months, P = .004). No important differences were found in any of a number of
      clinical characteristics based on causative organism or year of diagnosis.
      CONCLUSION: Acute epiglottitis has diminished in frequency since 1990. Patients
      whose conditions have been diagnosed since then tend to be older and to have
      disease caused by organisms other than H influenzae type b (particularly group A
      beta-hemolytic streptococcus). However, the clinical presentation appears to be
      similar to that seen previously.

PMID- 8143010
TI  - Eradication of Haemophilus influenzae type b disease in southern California.
      Kaiser-UCLA Vaccine Study Group.
AB  - OBJECTIVE: To assess the effects of Haemophilus influenzae vaccination of
      infants. RESEARCH DESIGN: We evaluated H influenzae type b (Hib) disease rates in
      Los Angeles County, California (population, 9 million; 1983 through 1992), and in
      the Southern California Kaiser Health Plan (2.5 million enrollees; 1988 through
      1992) during the past decade. Cases were obtained through active and passive
      disease surveillance in the two populations. The following vaccines were used
      during the study period (1983 through 1992): (1) Hib polysaccharide vaccine
      (polyribosyl ribitol phosphate) (used from 1985 through 1987 for children 24
      through 60 months of age); (2) Hib polysaccharide-diphtheria toxoid conjugate,
      Hib polysaccharide CRM197 mutant diphtheria toxoid conjugate vaccine, and Hib
      polysaccharide outer-membrane protein of group B meningococcus conjugate vaccine
      in older children (1988 through 1990; ages 15 through 60 months); and (3) Hib
      polysaccharide CRM197 mutant diphtheria toxoid conjugate vaccine and Hib
      polysaccharide outer-membrane protein of group B meningococcus conjugate vaccine
      used in infants (1991 through 1992). MEASUREMENTS AND RESULTS: Between 1983 and
      1988, the Hib disease incidence in Los Angeles County was unchanged (32.7 to
      42.5/100,000 person-years in children younger than 5 years). In 1989 through
      1990, before Hib conjugate licensure for infant use, Hib disease rates in all age
      groups declined. After licensure of Hib vaccines for infants in 1990, there was a
      further fivefold decrease in infants. More dramatic decreases occurred in the
      better-immunized Kaiser Health Plan children aged 0 through 60 months (53 cases
      in 1989, only two cases in 1992). CONCLUSIONS: The Hib disease has been nearly
      eradicated in a fully immunized population (Kaiser Health Plan), and significant
      reductions have also occurred in Los Angeles County.

PMID- 8143011
TI  - A search for persistent measles, mumps, and rubella vaccine virus in children
      with human immunodeficiency virus type 1 infection.
AB  - OBJECTIVE: To determine whether live measles, mumps, and rubella vaccine viruses
      persist after immunization of immunocompromised children with human
      immunodeficiency virus type 1 infection. METHODS: Ten children with symptomatic
      human immunodeficiency virus type 1 infection who received measles, mumps, and
      rubella immunizations were studied. Peripheral blood mononuclear cells,
      polymorphonuclear leukocytes, and plasma were cocultivated with primary African
      green monkey kidney tissue culture cells for detection of measles, mumps, and
      rubella viruses. Antibody to measles and mumps was determined by indirect
      fluorescent antibody and rubella was determined by enzyme-linked immunosorbent
      assay. Children seronegative to measles were revaccinated. RESULTS: Neither
      measles, mumps, nor rubella virus was recovered from peripheral blood mononuclear
      cells, polymorphonuclear leukocytes, or plasma in these children. No child
      experienced symptoms thought to be related to the vaccines. Humoral immunity
      after one or two immunizations was detected in 33% of the children. After
      vaccination, two of 10 children had IgG to measles; four of 10, to mumps; and
      four of 10, to rubella. CONCLUSIONS: In spite of an impaired humoral immune
      response, persistent viremia or infection did not occur after immunization with
      attenuated measles, mumps, and rubella vaccine viruses. These findings suggest
      that immunologic response to these viruses was sufficient to prevent persistent
      infection in these children immunocompromised by human immunodeficiency virus
      type 1 infection.

PMID- 8143012
TI  - Pathological case of the month. Subcutaneous fat necrosis of the newborn.

PMID- 8143013
TI  - Picture of the month. Fragile X syndrome.

PMID- 8143014
TI  - Radiological case of the month. Neonatal subgaleal hemorrhage.

PMID- 8143015
TI  - Decline of erythromycin resistance of group A beta-hemolytic streptococci in
      Japan. Comparison with worldwide reports.
AB  - OBJECTIVE: To determine the current prevalence of erythromycin resistance and
      penicillin tolerance of group A beta-hemolytic streptococci (GABHS) in Japan.
      RESEARCH DESIGN: One hundred four isolates of GABHS from the civilian community
      in Tokyo and 101 isolates from the military population at the US Air Force Base
      in Yokota, Japan, were tested for erythromycin susceptibility and penicillin
      susceptibility and tolerance. SETTING: US Army Medical Center. RESULTS: Of the
      Japanese civilian isolates, two were moderately susceptible and none were
      resistant to erythromycin; of the military isolates, none were moderately
      susceptible and one was resistant, for an overall resistance rate of 0.49%. All
      isolates were exquisitely susceptible to penicillin, and no evidence of
      penicillin tolerance was found. CONCLUSIONS: Comparison with similar studies
      world-wide shows that erythromycin susceptibility of GABHS in Japan is now among
      the lowest in the world, while just over a decade ago it was the highest. These
      observations mandate constant monitoring of erythromycin resistance of GABHS
      wherever this drug is used to treat patients with infections due to this
      organism.

PMID- 8143016
TI  - Lidocaine as a diluent for ceftriaxone in the treatment of gonorrhea. Does it
      reduce the pain of the injection?
AB  - OBJECTIVE: To compare the pain associated with ceftriaxone sodium injections by
      using two different diluents, ie, lidocaine hydrochloride and sterile water.
      DESIGN: Prospective study of adolescents who were culture positive for gonorrhea.
      Random selection of the diluent used for the intramuscular ceftriaxone therapy.
      SETTING: Urban, hospital-based adolescent medicine service. SUBJECTS: Thirty-nine
      adolescents and young adults, predominantly of black or Hispanic backgrounds,
      ranging in age between 14 and 23 years (mean age, 17.6 years; median age, 17
      years), of whom 27 were females. METHODS: Pain predictions were elicited from the
      adolescents before treatment. Pain ratings were obtained at five time intervals
      after the injections. All ratings were obtained by using a visual analog scale.
      RESULTS: No pain prediction differences before the injection were noted between
      the two groups. Individual t tests showed significant pain differences between
      the two groups at the time after the injection and at 10- and 20-minute and 6
      hour intervals. Repeated-measures analysis of variance models showed that the
      diluent effect on pain was significant. CONCLUSION: Lidocaine can reduce the
      amount of pain of an intramuscular injection of ceftriaxone when compared with
      sterile water as a diluent. These findings have implications not only for the
      treatment of gonorrhea but also for other situations where intramuscular
      injections utilizing a diluent may be necessary.

PMID- 8143017
TI  - A statewide evaluation of pediatric prehospital and hospital emergency services.
AB  - OBJECTIVE: To evaluate the extent of pediatric emergency training and the
      availability of pediatric equipment and patient care protocols in the prehospital
      and hospital settings. DESIGN: Statewide surveys developed by the North Carolina
      Provisional Committee on Pediatric Emergency Medical Services and by the Office
      of Emergency Medical Services. SETTING AND PARTICIPANTS: Surveys were mailed to
      all 572 prehospital Emergency Medical Service (EMS) agencies and separately to
      all 125 acute-care hospitals in North Carolina. INTERVENTIONS: None.
      MEASUREMENTS/MAIN RESULTS: Surveys were returned by 335 (58.6%) of the
      prehospital providers, including all 45 paramedic and 14 advanced-intermediate
      provider agencies. One hundred (80%) of the acute-care hospitals returned
      surveys. Only 10.8% of the prehospital EMS agencies provided more than 10 hours
      of basic training in pediatric emergency care; 18% provided more than 5 hours of
      continuing education in pediatric emergencies over a 3-year period. Pediatric
      specific equipment was available in many prehospital vehicles, although some
      deficiencies were noted. Written pediatric management, bypass, and helicopter
      transport protocols were absent in most prehospital programs. Paramedic programs
      generally were much better in all areas, although deficiencies were present. Only
      14% of the responding hospitals had more than 20 pediatric beds; 13% reported
      seeing more than 100 patients per day in the emergency department. Deficiencies
      were identified in pediatric patient care protocols, triage and transport
      agreements, pediatric training of nurses and physicians, and equipment. Equipment
      deficiencies were more marked in the intensive care units than in the emergency
      departments. CONCLUSIONS: These survey data are inexpensive to obtain and
      demonstrate EMS system deficiencies. The survey information provides a baseline
      measurement that can lead to measurable, targeted changes in the state's EMS
      system for children.

PMID- 8143018
TI  - Geographic patterns of fatal abuse or neglect in children younger than 5 years
      old, United States, 1979 to 1988.
AB  - OBJECTIVE: To examine geographic patterns of fatal child abuse or neglect (CAN)
      among children younger than 5 years old. DESIGN: A death certificate-based model
      to estimate the occurrence of fatal CAN. SETTING: United States, 1979 to 1988.
      PARTICIPANTS: The population of children younger than 5 years old. INTERVENTIONS:
      None. MAIN RESULTS: We estimate that from 868 to 1815 deaths annually occur among
      children younger than 5 years old from CAN. The lower figure is the estimate of
      confirmed CAN, and the higher is the estimate of the sum of confirmed, probable,
      and possible CAN. Death rates were highest in the South and West, intermediate in
      the North Central, and lowest in the Northeast. A threefold difference was noted
      between rates in the lowest- and highest-ranking states (ie, Connecticut, 2.9 to
      5.2 per 100,000, and Nevada, 6.7 to 15.4 per 100,000, respectively). When the 39
      largest metropolitan areas were ranked, a similar variation between the lowest
      and the highest was observed (ie, Boston, Mass, 2.7 to 5.5 per 100,000, and
      Phoenix, Ariz, 6.6 to 15.5 per 100,000, respectively). CONCLUSION: Understanding
      the sizable geographic variation in CAN deaths rates could lead to effective
      interventions. If the US fatality rate were reduced to that of Connecticut,
      between 434 and 908 fewer CAN deaths might occur annually.

PMID- 8143019
TI  - Termination of nutrition and hydration in a child with vegetative state.
AB  - A child in a vegetative state may present difficult decisions for physicians and
      families regarding the course of treatment. We report a case of a child who
      entered a prolonged vegetative state following status epilepticus. The child's
      parents requested termination of artificial means of nutrition and hydration.
      That request culminated in a complex legal intervention by multiple state
      agencies and attracted local media attention. This article presents the details
      of the case and discusses the medical and legal complexities encountered. The
      diagnosis and prognosis of the persistent vegetative state in children have
      recently been defined. Decision making in these circumstances should be based on
      adequate, careful clinical evaluation of the medical facts. Hospital ethics
      committees can provide an independent forum in which the diverse viewpoints in a
      case may be examined. Decision making should optimally be accomplished between
      families and caretakers.

PMID- 8143020
TI  - Athletic preparticipation examinations for adolescents. Report of the Board of
      Trustees. Group on Science and Technology, American Medical Association.
AB  - In response to a request from the House of Delegates to study the value of the
      preparticipation athletic examination for adolescents, the American Medical
      Association Board of Trustees prepared a report reviewing the current health
      status of adolescent athletes and the efficacy of trying to identify which
      athletes are at risk for injury and sudden death. It found that between 22% and
      39% of athletes sustain an injury that results in their not completing a practice
      or game or causes them to miss a subsequent practice or game. The existing state
      of information suggests that the preparticipation athletic examination is helpful
      in identifying adolescents at risk for orthopedic injury. The usefulness of the
      examination to identify adolescents at risk for sudden cardiac death or who have
      previously undiagnosed medical disorders is not substantiated by the research
      literature. The identification of orthopedic problems is maximized by the station
      approach. The guidelines developed in 1988 by the American Academy of Pediatrics
      provide the most current source on which conditions disqualify athletes from
      specific sports. Special care must be taken, however, to ensure that adolescents
      are not excluded unnecessarily from participation.

PMID- 8143021
TI  - Preparticipation physical examination. It should be required.

PMID- 8143022
TI  - [Impact of environmental pollution and smoking on the respiratory tract].

PMID- 8143023
TI  - [Comparison of the inhibition of the cutaneous histamine test by astemizole,
      loratadine, and terfenadine].
AB  - This article reviews a study which included 40 patients from the allergy out
      patient clinic and compared the reactions caused by three drugs in the dermal
      inhibition of histamine. All patients received subcutaneous histamine and were
      checked on different days. The size of the papule was compared before and after
      treatment. The reactions seen on day 20 were recorded and used for arriving at
      final conclusions. Astemizole showed better results than loratadine and
      terfenadine. Loratadine was seen to work better than terfenadine and the latter,
      better than the control group.

PMID- 8143024
TI  - [Cholera immunology and the molecular biology of cholera toxin. Recent progress
      and future prospects].
AB  - Cholera toxin (CT) and the analogous heat-labile enterotoxin (LT) from
      Escherichia coli have several immunomodulating effects that might explain their
      adjuvant action in stimulating secretory mucosal IgA after oral immunization. In
      mice experimental model, these effects include: enhanced antigen presentation by
      macrophages and other cell types; promotion of isotype differentiation in B cells
      leading to increased IgA formation; and other important effects on T cell
      proliferation and lymphokine production. The adjuvant activity is linked to the
      ADP-ribosylating action of CT with increased cyclic AMP formation in the affected
      cell, and thus it may be difficult to eliminate the enterotoxic activity without
      loss of adjuvanticity. However, both CT and its non-toxic B subunit moiety (CTB)
      have been shown to enhance the mucosal immune response to various epitopes or
      antigens covalently linked to these molecules. This now give promise that those
      antigens could become a useful vehicle to facilitate the induction of specific
      secretory IgA response to a broad range of antigens for human vaccination against
      cholera and other enteric infections.

PMID- 8143025
TI  - [Effect of occupational lead exposure on the immunoglobulin concentration and
      cellular immune function in man].
AB  - The evaluation of immunological conditions of 14 workers occupationally exposed
      to lead and comparison of these results with those of a non-exposed control group
      with similar age and sex were the aims of this study. It was determined the mean
      values of lead in blood. In exposed workers it was 46.9 ug/dl while in the
      control group it was 10.9 ug/dl. Levels of immunoglobulin decreasing while
      increasing lead concentration in blood were found in those exposed. It was also
      found a significant diminishment in the formation of rosette in relation to the
      control group.

PMID- 8143026
TI  - [Cellular immunity and vaccination against cutaneous leishmaniasis. Recent
      progress and prospects].
AB  - Review of leishmaniasis immunopathogenesis, the models in the laboratory animals,
      and the last advances in the experimental vaccine administration. In recent
      years, there have been important progresses that have contributed substantially
      to classify the role of the interleukins and other chemical mediators in the
      immunologic response. All these advances open the door to the production of
      better and more immunogenic vaccines, that in a near future will be employed
      advantageous in the human beings.

PMID- 8143027
TI  - Purification of tryptophan containing synthetic peptides by selective binding of
      the alpha-amino group to immobilised metal ions.
AB  - Immobilised metal ion affinity chromatography (IMAC) based on selective binding
      via the alpha-amino group to Cu2+ and Ni2+ ions has been used to purify
      tryptophan containing synthetic peptides. A free alpha-amino group, serving as an
      affinity handle, is present only in the target peptide when the peptides are
      synthesised by the solid-phase method and remaining amino groups after each
      coupling step are blocked by acetylation. A free alpha-amino group is necessary
      to retain the peptide on the column. The tryptophan residue may contribute to the
      binding only if the peptide is simultaneously anchored via the alpha-amino group.

PMID- 8143028
TI  - Application of gas chromatography-mass spectrometry and gas chromatography-tandem
      mass spectrometry to the analysis of chemical warfare samples, found to contain
      residues of the nerve agent sarin, sulphur mustard and their degradation
      products.
AB  - Samples of clothing, grave debris, soil and munition fragments, collected from
      the Kurdish village of Birjinni, were analysed by GC-MS with selected ion
      monitoring (SIM) for traces of chemical warfare agents and their degradation
      products. Positive analyses were confirmed, where possible, by full scan mass
      spectra, or at low concentrations by additional GC-MS-SIM analysis using chemical
      ionisation, by higher resolution GC-MS-SIM, and by GC-tandem mass spectrometry
      using multiple reaction monitoring. Sulphur mustard and/or thiodiglycol were
      detected in six soil samples; isopropyl methylphosphonic acid and
      methylphosphonic acid, the hydrolysis products of the nerve agent sarin, were
      detected in six different soil samples. Trace amounts of intact sarin were
      detected on a painted metal fragment associated with one of these soil samples.
      The results demonstrate the application of different GC-MS and GC-MS-MS
      techniques to the unequivocal identification of chemical warfare agent residues
      in the environment at concentrations ranging from low ppb to ppm (w/w). They also
      provide the first documented unequivocal identification of nerve agent residues
      in environmental samples collected after a chemical attack.

PMID- 8143029
TI  - Chromium determination by supercritical fluid chromatography with inductively
      coupled plasma mass spectrometric and flame ionization detection.
AB  - Supercritical fluid chromatography (SFC) has been investigated for the separation
      of a pair of beta-ketonate chromium compounds and a thermally labile
      organochromium dimer. A limited comparison between flame ionization detection
      (FID) and inductively coupled plasma mass spectrometric (ICP-MS) detection of
      these compounds is presented. The beta-ketonate complexes were observed with both
      detectors, while the thermally labile dimer was not observed with ICP-MS
      detection. Detection limits for these compounds with ICP-MS were in the range of
      0.9 to 3 pg with FID giving values between 10 and 250 pg. Reproducibility of the
      method is between 1 and 4% relative standard deviation (R.S.D.). The technique
      provided a linear response over approximately three orders of magnitude. The
      effect of two mobile phases (nitrous oxide and carbon dioxide) on the detection
      by each of the detectors are presented in a qualitative manner. Finally, the SFC
      ICP interface heating method and the manner in which the restrictor is heated in
      the FID system are compared and there effect on the chromatography discussed.

PMID- 8143030
TI  - Electrophoretically mediated microanalysis of calcium.
AB  - Electrophoretically mediated microanalysis (EMMA) was used for the determination
      of calcium. The faster analyte zone containing the calcium was injected spatially
      behind a slower zone of o-cresolphthalein complexone in a capillary
      electrophoresis based system. Upon application of the electric field the calcium
      zone was electrophoretically mixed with the reagent and product was formed. The
      bulk electroosmotic flow carried the product to the detector where the absorbance
      of the resulting complex at 575 nm was measured. Quantitation using an internal
      standard yielded a linear response with an R.S.D. of 8.1%. An inter-method
      comparison was performed with the standard bulk method and yielded results that
      did not significantly differ. The advantages of EMMA with respect to traditional
      methods were addressed.

PMID- 8143031
TI  - Competitive adsorption of alpha-lactalbumin and bovine serum albumin to a
      sulfopropyl ion-exchange membrane.
AB  - Breakthrough curves were measured for pure solutions of alpha-lactalbumin (ALA)
      and bovine serum albumin (BSA) individually, and for a binary mixture of the
      proteins, using a sulfopropyl ion-exchange membrane. The breakthrough curves were
      qualitatively consistent with local-equilibrium theory predictions. Competitive
      adsorption caused displacement of bound BSA monomer by the more strongly binding
      BSA dimer, illustrating that even apparently single-protein systems may display
      multicomponent competitive behavior. In the two-protein experiment, ALA was
      competitively displaced by the more strongly binding BSA monomer and dimer,
      indicating that the binding strength was in the order: BSA dimer > BSA monomer >
      ALA.

PMID- 8143032
TI  - Electroless plating--a new technique for the preparation of hard tissue specimens
      for scanning electron microscopy.
AB  - Specimens with complicated, intricate three-dimensional structures, which are
      otherwise difficult to coat adequately by conventional means (sputter or
      evaporative coating) for scanning electron microscopy, can quickly and simply be
      rendered conductive by electroless plating. The technique can be recommended only
      when studying specimens at low magnification because fine detail may be lost.

PMID- 8143033
TI  - The attachment of mineralised tissues to coverslips for observing dynamic events
      by confocal microscopy.
AB  - In confocal scanning optical fluorescence microscopy, using high-aperture oil
      immersion lenses, the best images are obtained for focus planes immediately under
      the coverslip, or under a continuation of the coverslip with a medium with the
      same, high refractive index. Therefore placing the coverslip with a layer of oil
      underneath it is an advantage if the sample will allow it. If experimental
      manipulations that can displace the coverslip are involved,--for example,
      attempts to make dynamic observation of fluid flow--the coverslip is best
      cemented to the sample with a high-index material. This report describes the use
      of adhesive systems developed for restorative dentistry to achieve a durable
      attachment of dental tissues to microscope coverslips. The technique described in
      this paper has been used for monitoring real-time fluid movement in dentine. The
      samples were examined with a high-frame-rate confocal microscope (a tandem
      scanning microscope). The adhesive technology also could be utilised in the
      microscopic preparation of other porous translucent materials.

PMID- 8143034
TI  - Effect of lung transplantation on right and left ventricular volumes and function
      measured by magnetic resonance imaging.
AB  - To evaluate the effect of lung transplantation on right ventricular (RV) and left
      ventricular (LV) volumes and function, magnetic resonance imaging (MRI) was
      performed in 11 patients before and 6 to 24 months after single (n = 7) or double
      (n = 4) lung transplantation as well as in 15 healthy control subjects. Prior to
      transplantation, RV end-diastolic (RVEDVI, ml/m2) and end-systolic (RVESVI,
      ml/m2) volume indices were significantly increased in patients compared with
      those in control subjects. RV ejection fraction (RVEF, %), although within the
      lower normal range, was significantly reduced. In contrast, LV volume indices
      (ml/m2) were significantly smaller in patients than in control subjects, whereas
      LV ejection fraction (LVEF, %) was not different from that in normal subjects.
      After lung transplantation, MRI revealed a significant reduction in RVEDVI from
      73 +/- 29 to 54 +/- 14 (p = 0.03) and RVESVI from 38 +/- 23 to 20 +/- 6 (p =
      0.01) with a concomitant significant increase in RVEF from 48 +/- 14 to 63 +/- 6
      (p = 0.01). Consecutively, the LV expanded to normal (LVEDVI from 49 +/- 12 to 65
      +/- 14, p = 0.01; LVESVI from 23 +/- 9 to 28 +/- 7, p = 0.05), whereas LVEF
      remained unchanged (55 +/- 9 versus 56 +/- 8).

PMID- 8143035
TI  - Fetal lung growth. Influence of pulmonary arterial flow and surgery in sheep.
AB  - Aberrant pulmonary arterial flow has been associated with pulmonary hypoplasia,
      which is a common cause of death in newborns. The current experiments were
      designed to confirm whether interruption of postductal main pulmonary artery
      (MPA) flow causes pulmonary hypoplasia. In addition, the effect of fetal surgery
      on lung growth was investigated. Fetal sheep, instrumented at 107 to 115 d
      gestation (MPA ligated [n = 5], sham operated [n = 3], and monitored [no
      thoracotomy, n = 5]), and unoperated twin fetuses (140-d controls, n = 5) were
      used for analysis of lung growth at 136 to 140 d gestation. Morphometric
      measurement of lung tissue volumes and assays of DNA, protein, and saturated
      phosphatidylcholine (SPC) were used to assess lung growth. MPA ligation
      significantly decreased lung growth and maturation as indicated by decreased
      surface area and volumes of fine nonparenchyma, future airspace, and parenchymal
      tissue, and by decreased lung weights, total DNA, protein, and SPC content. There
      was a significant increase in the volume percentage of coarse nonparenchyma and a
      decrease in the volume percentage of future airspace. The pattern of lung growth
      after MPA ligation suggests that growth of peripheral airspace and parenchymal
      tissue components does not occur, resulting in a significant decrease in the
      amount of new tissue formed and delayed tissue maturation. Fetal surgery
      significantly changed only DNA, protein, and SPC content. Studies of the
      regulation of lung growth must consider the role of pulmonary arterial flow and
      the smaller, but significant effects of fetal surgery.

PMID- 8143036
TI  - Airway effects of local challenge with hypertonic saline in exercise-induced
      asthma.
AB  - Hypertonicity of airway lining fluid has been suggested as the stimulus for
      bronchoconstriction in exercise-induced asthma. We explored the airway effects of
      delivering a direct hypertonic stimulus to asthmatic airways via a fiberoptic
      bronchoscope, comparing hypertonic saline challenge by direct instillation with
      local aerosol delivery. A group of 18 asthmatic subjects responsive to inhaled
      hypertonic saline with a history of EIA were studied; the first 9 subjects
      received local challenge with hypertonic saline by direct instillation, and the
      next 9 subjects were challenged by local aerosol delivery. A control challenge
      with isotonic saline by either instillation or aerosol was performed at a same
      bronchoscopy. Local challenge with hypertonic saline by aerosol delivery was
      found to be more effective in inducing local bronchoconstriction (8 of 9
      subjects) than instillation (2 of 6 subjects). Paired BAL fluid samples and
      bronchial biopsies were obtained in total of 11 and 9 subjects, respectively.
      Local challenge with hypertonic saline either by instillation or aerosol produced
      no significant change in histamine, tryptase, or PGD2 levels in BAL fluid or mast
      cell numbers and degranulation in bronchial biopsies. A significant correlation
      was observed between histamine levels in BAL fluid and airway responsiveness to
      inhaled hypertonic saline (rs = -0.59, p < 0.05). Bronchial biopsies showed
      evidence of extensive epithelial damage; however, this was not related to airway
      responsiveness to inhaled hypertonic saline.

PMID- 8143037
TI  - Infectious complications of Swan-Ganz pulmonary artery catheters. Pathogenesis,
      epidemiology, prevention, and management.

PMID- 8143038
TI  - Elevated levels of interleukin-8 and leukotriene B4 in pulmonary edema fluid of a
      patient with reexpansion pulmonary edema.
AB  - We experienced a case of reexpansion pulmonary edema (RPE) after surgical
      treatment of pneumothorax. In this case, protein leakage and polymorphonuclear
      leukocyte (PMN) accumulation were observed in the reexpanded lung. Interleukin-8
      and leukotriene B4 in edema fluid were increased at the onset of RPE. PMN
      elastase was also increased, though its peak was delayed. The plasma level of P
      selectin, which mediates adhesion between PMN and endothelium, was elevated. We
      speculate that some of these fluid mediators may play important roles in
      chemotaxis and activation of PMN in the development of RPE.

PMID- 8143039
TI  - Pulmonary Kaposi's sarcoma revealed by a solitary nodule in a patient with
      acquired immunodeficiency syndrome.
AB  - Kaposi's sarcoma is very common in patients with AIDS. Usually, skin lesions are
      associated with various visceral involvements. A homosexual patient with AIDS
      presented with cough and dyspnea, which were followed months later by hemoptysis.
      He had no skin lesions or endobronchial Kaposi's sarcoma at any time. His chest
      radiograph showed only an irregular solitary nodule. It exhibited very slow
      development over time. Surgery was performed, and this solitary nodule proved to
      be pulmonary Kaposi's sarcoma. Pulmonary Kaposi was the sole manifestation of
      this associated AIDS sarcoma. This very unusual case report of pulmonary Kaposi
      sarcoma indicates that this diagnosis should be considered in patients with AIDS
      presenting with a solitary pulmonary nodule.

PMID- 8143040
TI  - Noninvasive tests for acute venous thromboembolism.

PMID- 8143041
TI  - Mechanisms of disease: are oxygen-derived free radicals involved in diaphragmatic
      dysfunction?

PMID- 8143042
TI  - Role of hyperventilation in the pathogenesis of central sleep apneas in patients
      with congestive heart failure.

PMID- 8143043
TI  - Role of hyperventilation in the pathogenesis of central sleep apneas in patients
      with congestive heart failure.

PMID- 8143044
TI  - Bicarbonate does not increase left ventricular contractility during L-lactic
      acidemia in pigs.

PMID- 8143045
TI  - Blood gas monitors justifiable enthusiasm with a note of caution.

PMID- 8143046
TI  - Development of a patient-dedicated, on-demand, blood gas monitor.
AB  - A new monitor (CDI 2000) that brings blood gas measurements to the patient's
      bedside has been developed. To measure blood gases, blood is drawn into the
      patient's arterial pressure-monitoring line past in-line fluorescent-based
      sensors. After measurement, the blood is returned to the patient, avoiding blood
      loss and delays in sample turnaround and reducing the risk of infection to both
      patient and operator. We assessed this system's performance in vitro with
      tonometered bovine blood. Bias (mean difference between monitor and tonometered
      gas or measured pH values) +/- the standard deviation (SD) were 0.01 +/- 0.02 at
      pH = 7.39; 0.0 +/- 0.7 mm Hg at Pco2 = 39 mm Hg; and 2.4 +/- 3.2 mm Hg at a Po2 =
      100 mm Hg (n = 54). Changes in hematocrit, blood temperature, or serum sodium
      concentration did not have clinically significant effects on system performance.
      Studies in normal volunteers, in whom large changes in blood gases were induced,
      showed a bias (mean difference between monitor and IL 1306 values) +/- SD of 0.00
      +/- 0.02 for pH, -0.4 +/- 2.0 mm Hg for Pco2, and -3.6 +/- 7.7 mm Hg for Po2 (n =
      69). We conclude from the present study that the performance of this system is
      comparable to that of conventional blood gas analyzers.

PMID- 8143047
TI  - Bronchoalveolar lavage for diagnosing bacterial pneumonia in mechanically
      ventilated patients.
AB  - To assess the usefulness of BAL in diagnosing bacterial pneumonia in mechanically
      ventilated patients, 80 BAL fluid samples obtained from 72 patients with lung
      infiltrates were studied using the following parameters: infected cell count
      (polymorphonuclear leukocytes or macrophages with intracellular organisms),
      microscopic examination of stained smears, and quantitative culture with the
      determination of the simplified bacterial index (SBI) and the predominant species
      index (PSI). Of the 80 BAL samples studied, 56 were performed under antibiotic
      therapy. Bacterial pneumonia was the final diagnosis in 28 cases. The SBI is the
      sum of the whole numbers of each bacterial concentration expressed as a common
      logarithm. The PSI is the whole number of the predominant microorganism's
      concentration expressed as a common logarithm. The discriminative value of each
      test was assessed using a receiver operating characteristic (ROC) curve, whereby
      the possibility of establishing a cutoff value used to discriminate between the
      presence or absence of pneumonia is evaluated. The percentage of infected cells
      was higher in the pneumonia group (8.8 +/- 18.1 versus 0.4 +/- 1.1%, p < 10(-3),
      but no cutoff value could be proposed. Under microscopic examination, the
      presence of bacteria was noted with a significantly greater frequency in the
      pneumonia group (sensitivity 67.8% and specificity 82.7%). A total of 58 BAL
      samples were positive when cultured. The SBI was significantly higher in the
      pneumonia group (6.5 +/- 2.9 versus 1.6 +/- 1.7, p < 10(-4).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8143048
TI  - Increase in filtration coefficient from actions of melittin on neutrophils in
      isolated rabbit lungs.
AB  - Activation of neutrophils may contribute to lung injury in the adult respiratory
      distress syndrome. We added rabbit neutrophils to the pulmonary circulation of
      salt-perfused and ventilated isolated rabbit lungs. These neutrophils were
      activated by adding synthetically pure melittin to the perfusate. This led to
      lung injury as measured by filtration coefficient under no-flow conditions. We
      also activated neutrophils in vitro before addition to the pulmonary circulation.
      These preactivated neutrophils also produced lung injury, indicating a primary
      action of melittin on neutrophils rather than on lung. The injury was prevented
      by aristolochic acid, which is an inhibitor of phospholipase A2 (PLA2), and
      independently by catalase, which is scavenger of hydrogen peroxide (H2O2).
      Aristolochic acid also appeared to act primarily on neutrophils since addition to
      neutrophils in vitro prevented injury from in vitro activation by melittin.
      Aristolochic acid did not appear to act as a free radical scavenger since it did
      not prevent injury from neutrophils activated by phorbol myristate acetate (PMA).
      PMA is a direct activator of protein kinase C in neutrophils and leads to
      formation of H2O2 with consequent lung injury. We conclude that activation of
      neutrophils by melittin leads to oxidant lung injury possibly from activation of
      PLA2. Since PLA2 does not directly produce a second messenger, such as
      diacylglycerol or inositol triphosphate, it is likely that other actions of PLA2
      produce an intermediary mediator. We previously showed that an inhibitor of
      eicosanoid synthesis prevents lung injury from exogenous PLA2. This suggests that
      the formation of leukotriene B4 (LTB4), a 5-lipoxygenase product of arachidonic
      acid, may contribute to the oxidant lung injury from melittin.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8143049
TI  - Eicosanoids decrease with successful extracorporeal membrane oxygenation therapy
      in neonatal pulmonary hypertension.
AB  - Elevated concentrations of eicosanoids have been reported in bronchoalveolar
      lavage fluid (BALF) and blood of infants with persistent pulmonary hypertension
      (PPHN), thereby indicating their potential role in its pathophysiology.
      Extracorporeal membrane oxygenation (ECMO) has improved the outcome in selected
      infants with PPHN. We hypothesized that ECMO, by alleviating lung injury, would
      be associated with decreased eicosanoid production and clinical improvement.
      Twenty-two newborns with PPHN treated with either ECMO or conventional means were
      studied. Concentrations of TxB2, 6-keto-PGF1 alpha, PGD2, PGE2, LTB4, and LTE4
      were serially measured in BALF. Elevated concentrations of all eicosanoids
      measured were observed in all infants with PPHN at the initiation of ECMO.
      Eicosanoid concentrations decreased in all infants with a good clinical outcome
      after ECMO, but they remained elevated in those with a poor outcome. In patients
      with less severe PPHN, not requiring ECMO, lower concentrations of eicosanoids
      were observed at initiation of therapy. Eicosanoid levels increased or did not
      change over the course of conventional treatment. We conclude that eicosanoids
      are present in high concentrations in infants with PPHN. Iatrogenic factors,
      including oxygen and barotrauma, appear to correlate with their concentrations.
      Removal of these factors is associated with decreased production of mediators and
      clinical improvement.

PMID- 8143050
TI  - Nature of pulmonary hypertension in congestive heart failure. Effects of cardiac
      transplantation.
AB  - Pulmonary hypertension associated with congestive heart failure carries a risk of
      right ventricular failure after cardiac transplantation. Few data, however, are
      available on the hemodynamic behavior of the pulmonary circulation in these
      patients. We therefore studied mean pulmonary artery pressure minus left atrial
      pressure (estimated by pulmonary artery occluded pressure) versus cardiac output
      relationships in 20 patients with congestive heart failure evaluated for
      orthotopic cardiac transplantation, and we repeated this study either within the
      first 3 days postoperatively (n = 10) or 1 month postoperatively (n = 11).
      Cardiac output was increased by physical exercise or (in the early postoperative
      period) by an infusion of dobutamine. Reversibility of pulmonary hypertension was
      tested by an infusion of prostaglandin E1. At preoperative evaluation, the
      extrapolated pressure intercept of pulmonary vascular pressure:flow plots was
      negative in 10 of the patients, suggesting active exercise-induced pulmonary
      vasoconstriction. In the other 10 patients, the extrapolated pressure intercept
      was positive, suggesting that an increased closing pressure contributed to
      pulmonary hypertension. However, transplantation was constantly associated with
      proportional decreases of pulmonary artery pressure and left atrial pressure. On
      the other hand, pulmonary vascular pressure:flow plots were displaced to equal or
      lower pressures and to higher flows by prostaglandin E1 before as well as after
      transplantation. We conclude that in patients with congestive heart failure
      evaluated for cardiac transplantation, an increased pulmonary venous pressure
      more than a reversible increase in closing pressure determines the severity of
      pulmonary hypertension.

PMID- 8143051
TI  - Energy-dispersive X-ray analysis and scanning electron microscopy of pleura.
      Study of reference, exposed non-pneumoconiotic, and silicotic populations.
AB  - Inorganic element content in pleura and lung was studied by energy-dispersive X
      ray analysis (EDXA) and scanning electron microscopy (SEM) in reference, exposed
      non-pneumoconiotic, and silicotic populations. Samples of parietal pleura,
      visceral pleura, and lung in 11 subjects with no measurable exposure to inorganic
      dust and of visceral pleura and lung samples of 10 exposed non-pneumoconiotic
      individuals and eight silicotic patients were examined. Constant depositions of
      silicon and calcium were detected in visceral pleura, parietal pleura, and lung
      of the reference group and in visceral pleura and lung of the exposed non
      pneumoconiotic and silicotic groups. Other elements, such as aluminum and iron,
      were also detected in the exposed non-pneumoconiotic and silicotic patients and,
      less frequently, in the reference group. There was no difference in silicon
      content between parietal and visceral pleura in the reference group. Silicon
      content in silicotic patients was higher and more irregularly distributed in the
      pleura (p = 0.005 and p < 0.01, respectively) and in the lung (p = 0.005 and p <
      0.01, respectively) than in the reference group. Comparison of the silicon
      content in pleura between silicotic and exposed non-pneumoconiotic subjects
      showed a nonsignificant probability of difference (p = 0.052), whereas there were
      no differences with respect to the silicon content in lung. There were no
      differences in the pleural and lung silicon content between the exposed non
      pneumoconiotic and reference groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143052
TI  - Outcome of the treatment for sarcoidosis.
AB  - The clinical characteristics and pathology of sarcoidosis are well defined;
      however, the optimal therapy for this disorder remains unclear. Although patients
      respond, acutely, to corticosteroid therapy, it is not clear that these agents
      ultimately alter the natural history of this disease. These observations and that
      corticosteroids have significant side effects suggest that only patients who will
      clearly benefit from corticosteroid therapy should be treated. In a prospective
      study of patients' with sarcoidosis (n = 98), we limited our use of
      corticosteroids to those patients who had objective evidence of recent
      deterioration in lung function or serious extrapulmonary disease. All patients
      with sarcoidosis fulfilling these criteria were treated with corticosteroids.
      Patients were tapered off corticosteroids after they were treated for 1 yr. Of
      the 98 study subjects, 91 had not received therapy for the disease and 7 were on
      therapy before entry into the study. Of the 91 previously untreated patients, 55
      were observed without therapy and 36 were treated with corticosteroids. Of those
      who were observed off therapy, only eight deteriorated. Of these latter patients,
      six responded and stabilized with the administration of corticosteroids for
      treatment of the underlying disease, to antibiotics for an associated
      bronchiectasis, or to diuretics for treatment for congestive heart failure; two
      were lost to follow-up. None of these six patients deteriorated while receiving
      corticosteroids. Of the 36 patients who deteriorated and were treated with
      corticosteroids, 20 remained stable and 16 improved clinically. Of the 37
      patients who were eventually tapered off corticosteroids, five deteriorated and
      required reinitiation of corticosteroid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143053
TI  - Host determinants of cellular and biochemical constituents of bronchoalveolar
      lavage fluids. Implications for design of epidemiologic studies.
AB  - The effects of demographic characteristics, exercise, environmental exposures,
      and other host factors on cellular and biochemical constituents of human
      bronchoalveolar lavage (BAL) fluids were investigated by studying more than 300
      specimens obtained from normal volunteers and assayed in a single center. The BAL
      data demonstrated associations with race, smoking, exercise, skin-test reactions,
      and blood constituents, and weak or no associations with age, sex, pulmonary
      function tests (PFT), or ambient ozone exposure. The effect of exercise was
      relatively strong and more clearly characterized than in previous studies.
      Smoking effects were similar to those observed in other studies; our ability to
      study age and ambient ozone effects was greatly limited because of the
      homogeneity of the population under study. Blood constituents of the subjects
      also showed an association with level of exercise. Analysis of intraindividual
      and interindividual variability in BAL constituents results suggested that
      matching, although desirable, is not essential for the maintenance of adequate
      statistical power in BAL studies, so observational studies of the effects from
      air pollution on BAL fluids in humans could be effectively conducted using cross
      sectional designs.

PMID- 8143054
TI  - Efficacy of a Herbst mandibular advancement device in obstructive sleep apnea.
AB  - Treatment options for obstructive sleep apnea (OSA) may involve potential side
      effects or discomfort; nasal continuous positive airway pressure (CPAP) may not
      be tolerated by 25% of patients. We therefore sought to determine the efficacy of
      mandibular advancement as a treatment for OSA, and to investigate whether
      clinical and radiographic parameters can predict the response to this treatment.
      Sixteen male and 3 female subjects with documented OSA who had failed or been
      unable to tolerate nasal CPAP underwent baseline polysomnography and
      cephalometry, and were then fitted with a removable Herbst appliance to achieve
      forward mandibular advancement during sleep. All subjects then underwent a second
      cephalometric evaluation and polysomnography with the appliance in place.
      Fourteen of 15 subjects demonstrated significant improvement in the degree of
      OSA, based on the apnea-hypopnia index (AHI) (34.7 +/- 5.3 to 12.9 +/- 2.4
      events/h, p < 0.002). Comparison of pre- and posttreatment cephalometric values
      revealed no significant change in the posterior airway space (PAS) despite a
      reduction in mean AHI. There was a significant decrease in the mandible-hyoid
      distance (MP-H) with treatment for the group as a whole. When the study
      population was evaluated on the basis of a successful response to mandibular
      advancement (posttreatment AHI < 10), the baseline MP-H was found to be
      significantly shorter in the responders than in nonresponders. MP-H after
      mandibular advancement was likewise shorter in responders than in nonresponders.
      In addition, the soft palate length (PNS-P) showed a significantly greater
      shortening in responders after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143055
TI  - Role of adenosine in the depolarization of hypoxic hamster diaphragm membrane in
      vitro.
AB  - The resting membrane potential of in vitro hamster diaphragm muscle fibers is
      depolarized on exposure to hypoxia. It was hypothesized that this depolarization
      was mediated by adenosine. It was predicted that the treatment of well-oxygenated
      hamster diaphragm muscle strips in vitro with adenosine or adenosine agonists
      would depolarize the diaphragm fiber membrane. Furthermore, resting membrane
      potential of hypoxic diaphragm fibers would be repolarized by (1) the removal of
      adenosine by the enzyme adenosine deaminase (ADA), or (2) the addition of an
      adenosine antagonist, BW A1433. Adenosine (10(-4) M) depolarized the membrane by
      8 +/- 1 mV (p < 0.001). The adenosine agonist cyclopentyladenosine, which has
      predominantly A1 receptor affinity, depolarized the membrane from -75.4 +/- 5.6
      mV to -68.9 +/- 5.7 mV (p < 0.001). The A2 adenosine receptor agonist 5'-N
      ethylcarboxamide adenosine did not cause a significant depolarization. The
      addition of ADA (2 unit/ml) to hypoxic muscle returned the resting membrane
      potential to that of well-oxygenated fibers, p < 0.001 versus hypoxia. BW A1433
      (3 x 10(-7)) also restored the membrane potential of hypoxic muscle fibers from 
      72 +/- 1 mV to -79 +/- 1 mV (p < 0.001). These observations suggest that
      adenosine via the A1 adenosine receptor mediates the hypoxic depolarization of in
      vitro hamster diaphragm muscle. A direct effect of adenosine on muscle membrane
      has not been described previously.

PMID- 8143056
TI  - Inotropic effects of theophylline on foreshortened canine diaphragm.
AB  - We previously demonstrated that theophylline exerted greater inotropic effects on
      foreshortened canine diaphragm than on diaphragm placed at resting length in vivo
      (1). To ensure that these effects result from an effect on the muscle itself,
      they were examined in vitro. Thus, the effects of increasing doses of
      theophylline (20, 100, 200, and 400 mg/L) or addition of Krebs solution on twitch
      tension (Pt) of bundles placed at optimal length (Lo) and 70% Lo were compared.
      At Lo, compared with time-matched control, Pt significantly increased after
      theophylline (e.g., 37 +/- 32 versus -8 +/- 12% after 400 mg/L) except with 20
      mg/L. At 70% Lo, Pt increased with all theophylline concentrations in a dose
      related manner (e.g., 14 +/- 15 versus -6 +/- 7% and 114 +/- 57 versus -8 +/- 11%
      after 20 and 400 mg/L, respectively). Time to peak tension and half-relaxation
      time remained unchanged after theophylline both at Lo and 70% Lo. In addition,
      for a given concentration, twitch potentiation was significantly greater at 70%
      Lo than at Lo, the difference increasing with increasing concentration (e.g., 3
      times greater with 400 mg/L). We conclude that theophylline-induced inotropic
      effects on Pt were more pronounced on foreshortened canine diaphragm bundles than
      on bundles placed at Lo. These observations confirm that theophylline-induced
      inotropic effects on foreshortened muscle previously observed in vivo are likely
      to result from a direct effect on muscle contractility.

PMID- 8143057
TI  - Ventilatory load characteristics during ventilatory muscle training.
AB  - The response of skeletal muscle to training is influenced by both the intensity
      and nature of the training stimulus. In this study we investigated the
      characteristics of the ventilatory load applied to the ventilatory muscles during
      several different modes of ventilatory muscle training. Patients with chronic
      obstructive pulmonary disease (COPD) performed the following breathing maneuvers:
      (1) Unloaded hyperpnea (UH), (2) resistive breathing through a fixed orifice (0.5
      cm diameter) at frequencies of 15 and 30 breaths/min (RT15, RT30), (3) loaded
      breathing through a threshold valve set at 30% of the PImax at frequencies of 15
      and 30 breaths/min (TT15, TT30), and (4) repetitive maximal inspiratory maneuvers
      against a closed shutter (PImax). During these maneuvers were recorded airflow
      and pressures at the month and esophagus, and from these measurements we derived
      VE and the work of breathing (WOB), tension time index (TTI), and pressure time
      product (PTP). The VE during UH was significantly higher than all other modes (p
      < 0.01), whereas the Pesmax was significantly lower during UH than during the
      resistive and loaded maneuvers (p < 0.01). The WOB did not differ during UH,
      TT30, and RT30, but was significantly higher in all three modes than at TT15 and
      RT15 (p < 0.05). During RT30 the TTI was higher than during TT30, TT15, and RT15
      (p < 0.05), whereas the TTI during UH was significantly lower than during other
      maneuvers (p < 0.01). As expected, the highest Pesmax and PTP were found during
      the PImax maneuver. These data show that important qualitative differences in
      ventilatory muscle loading can be achieved by means of different devices and
      breathing strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143058
TI  - Anxiety and depression in relation to respiratory symptoms and asthma.
AB  - The aim of this investigation was to study the relationship between psychologic
      status and respiratory health. The study comprised 715 persons aged 22 to 44 who
      participated in the European Commission Respiratory Health Survey. The study
      included a structural interview, spirometry, methacholine challenge, peak flow
      diary, skin prick test, and measurement of eosinophil activity in peripheral
      blood. The psychologic status was assessed by means of the hospital anxiety and
      depression (HAD) scale questionnaire. A significant correlation was found between
      anxiety and depression and the report of asthma-related symptoms, such as attacks
      of breathlessness after activity and waking with attacks of breathlessness (p <
      0.01). However, there was no significant correlation between anxiety or
      depression and a self-reported diagnosis of asthma or objective asthma-related
      variables, such as peak flow variability or response to methacholine. When
      evaluating the combined influence of psychologic factors and objective variables,
      HAD score correlated independently with reported wheezing (p < 0.05), waking with
      attacks of breathlessness (p < 0.01), waking with chest tightness, attacks of
      breathlessness when at rest, and attacks of breathlessness after activity (p <
      0.001). We conclude that there is an association between reported respiratory
      symptoms and psychologic status. However, there was no evidence that patients
      with diagnosed bronchial asthma had more anxiety and depression than those
      without asthma. This result indicates that it may be valuable to include
      psychologic status indicators in respiratory symptom questionnaires.

PMID- 8143059
TI  - Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with
      asthma after aspirin challenge.
AB  - We have recently shown that oral aspirin provocation leads to an increase in LTE4
      and a reduction in 11-dehydro-TXB2 levels in urine of patients with aspirin
      induced-asthma (AIA). To test the hypothesis that cyclooxygenase inhibition and
      an enhancement of cysteinyl-leukotriene production occurs in the lungs of
      patients with AIA, we examined the eicosanoid levels in bronchoalveolar lavage
      fluid obtained 30 min after lysine-aspirin or placebo inhalation in 10 patients
      with AIA. Eosinophil cationic protein (ECP) levels were determined to evaluate
      eosinophil activation. Six asthmatics nonsensitive to aspirin (NA) underwent
      challenge with placebo. The dose of lysine-aspirin inhaled by patients with AIA
      was equal to that which had produced > or = 20% fall in FEV1. Compared with NA,
      patients with AIA had: (1) eicosanoid levels, particularly PGE2 and TXB2,
      elevated and (2) higher number of eosinophils and ECP. The overproduction of
      eicosanoids could be related to a distinct eosinophilic inflammation in airways
      of patients with AIA. Inhalation of lysine-aspirin had no effects on 12-HETE and
      15-HETE levels, but it markedly depressed cyclooxygenase products and
      significantly enhanced leukotriene production in the lungs of patients with AIA.

PMID- 8143060
TI  - Blood and bronchoalveolar lavage endothelin-1 levels in nocturnal asthma.
AB  - Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that was recently
      shown to exhibit bronchoconstrictive properties in vitro. In asthmatic patients,
      the expression of ET-1 peptide was also shown to be increased in endobronchial
      biopsies. Thus, we postulated that ET-1 could be higher in subjects with
      nocturnal asthma. Bronchoalveolar lavage (BAL) fluid levels of ET-1 were measured
      in 10 subjects with nocturnal asthma and 6 normal volunteers at 0400 h (nighttime
      groups) and in an additional 7 subjects with nocturnal asthma and 6 control
      subjects at 1600 h (daytime groups). ET-1 levels were significantly lower in the
      nighttime asthmatic group (median 39.3 pg/mg protein, 7.3 to 44.0 IQ) than in the
      nighttime control group (median 77.4 pg/mg protein, 46.8 to 121.9 IQ; p = 0.01)
      or the daytime asthmatic group (median 56.8 pg/mg protein, 51.6 to 97.4 IQ; p =
      0.04). ET-1 levels did not differ significantly between the daytime asthmatic and
      the daytime control groups or between control groups. Additionally, the overnight
      reduction in lung function was significantly correlated with lower BAL ET-1
      levels (r = 0.57, p = 0.05). These results suggest that ET-1 plays a role in the
      overnight worsening of asthma and perhaps is more tightly tissue bound, resulting
      in lower levels of BAL fluid.

PMID- 8143061
TI  - Effect of oral prednisone on airway inflammatory mediators in atopic asthma.
AB  - The mechanism of steroid action in asthma is unknown. Because steroids have
      effects in vitro on eicosanoid synthesis, we determined the effect of oral
      prednisone for 6 to 9 days on eicosanoid levels in bronchoalveolar lavage (BAL)
      fluid of 14 atopic asthmatic volunteers at baseline and after allergen
      instillation. We also determined the effect of prednisone on the ex vivo release
      of eicosanoids from macrophage-rich BAL-fluid cells. Prednisone reduced symptoms
      and inhaler use but had no significant effect on BAL-fluid eicosanoid levels. At
      baseline, prostaglandin D2 (PGD2) levels were 101 +/- 37 pg/ml in BAL fluid (mean
      +/- SEM), versus 66 +/- 18 pg/ml after prednisone; likewise, 5-hydroxy
      eicosatetraenoic acid (5-HETE) levels were 59 +/- 15 versus 78 +/- 21;
      leukotriene E4 (LTE4) levels were 35 +/- 13 versus 51 +/- 21, and 15-hydroxy
      eicosatetraenoic acid (15-HETE) levels were 29 +/- 8 versus 19 +/- 7. Allergen
      stimulated levels of PGD2 were 1274 +/- 565 versus 1468 +/- 679 after prednisone;
      likewise, allergen-stimulated 5-HETE levels were 95 +/- 21 versus 82 +/- 21;
      those of LTE4 were 54 +/- 20 versus 91 +/- 51; and those of 15-HETE were 63 +/-
      19 versus 60 +/- 25. Prednisone reduced the synthesis of eicosanoids in
      macrophage-rich BAL-fluid cells in vitro. LTB4 levels fell significantly from 35
      +/- 6.4 ng/10(6) BAL-fluid cells to 17 +/- 5.4 after prednisone; likewise, levels
      of thromboxane B2 (TXB2) fell from 35.7 +/- 7.5 to 20.7 +/- 6.6. Part of the
      action of steroids may involve alteration in macrophage eicosanoid synthesis.

PMID- 8143062
TI  - Chronic fenoterol exposure increases in vivo and in vitro airway responses in
      guinea pigs.
AB  - We tested the hypothesis that the regular inhalation of a beta 2-adrenergic
      receptor (beta 2AR) agonist increases airway responsiveness in guinea pigs. A
      potent beta 2AR agonist, fenoterol hydrobromide, in sublaryngeal doses equivalent
      to maximal doses used in the treatment of asthma on a weight basis (5.28
      micrograms/kg), was administered by nebulizer three times a day for 6 weeks to
      normal adolescent guinea pigs (FEN, n = 10) and to ovalbuminsensitized guinea
      pigs challenged twice weekly with ovalbumin (OA + FEN, n = 20), although not in
      the 12 h prior to or 4 h after antigen challenge. Controls included saline
      treated normal animals (CON, n = 10) and ovalbumin-sensitized animals treated
      with repeated antigen challenge and saline (OA, n = 20). At 72 h after the last
      administration of saline, fenoterol, and ovalbumin, the dose-response
      relationship between pulmonary resistance (RL) and nebulized acetylcholine (ACh)
      was measured. RLmax increased 2-fold and the ACh concentration causing a 10-fold
      increase in RL (PC10) decreased 4-fold in the FEN, OA, and OA + FEN groups as
      compared to the CON group. In the FEN, OA, and OA + FEN groups, in vitro tracheal
      smooth-muscle contractile responses to maximal concentrations of acetylcholine
      increased 2-fold, and this increase was not due to increased smooth-muscle mass.
      There was no evidence for beta 2AR desensitization as judged by in vitro tracheal
      smooth-muscle relaxant responses to fenoterol. These results suggest that chronic
      beta 2AR stimulation increases airway smooth-muscle contractility and in vivo
      airways responsiveness to a degree similar to that induced by chronic antigen
      exposure. A similar effect in human asthmatics may explain the adverse effects
      observed during prolonged treatment with these drugs.

PMID- 8143063
TI  - The proteinase-antiproteinase balance in alpha-1-proteinase inhibitor-deficient
      lung transplant recipients.
AB  - We examined the proteinase-antiproteinase balance in the bronchoalveolar lavage
      (BAL) fluid from alpha-1-proteinase inhibitor (alpha 1PI)-deficient lung
      transplant recipients to determine whether they would derive benefit from
      intravenous augmentation therapy with alpha 1PI. BAL fluid from 11 alpha 1PI
      deficient lung transplant recipients and eight control subjects was assayed for
      free neutrophil elastase activity, immunoreactive alpha 1PI, and elastase
      inhibitory capacity. Samples were obtained during intervals of health and
      respiratory illness. BAL fluid from healthy alpha 1PI-deficient lung transplant
      recipients had minimal or unmeasurable free elastase activity, which was not
      different from that of control subjects. alpha 1PI concentrations in BAL fluid
      from alpha 1PI-deficient lung transplant recipients were reduced when compared
      with those of control subjects. Despite this observation, all but one alpha 1PI
      deficient patient had the ability to inhibit exogenous elastase. During
      respiratory illness, however, three of seven alpha 1PI-deficient lung transplant
      recipients had measurable free elastase activity, which was inhibited ex vivo by
      addition of alpha 1PI. We conclude that alpha 1PI-deficient lung transplant
      recipients demonstrate free elastase activity in BAL fluid during severe lower
      respiratory tract inflammation, which is not present during health. Intravenous
      supplementation of alpha 1PI-deficient lung transplant recipients with exogenous
      alpha 1PI during respiratory tract inflammation may be indicated to inhibit
      elastase-mediated injury to the transplanted lung.

PMID- 8143064
TI  - Gamma-delta T cells in sarcoidosis. Correlation with clinical features.
AB  - This study investigated the relationship between the clinical features of
      sarcoidosis and the level of peripheral blood gamma-delta (gamma delta) T cells.
      Both the mean percentage of T cells and the mean cell number of gamma delta T
      cells in the peripheral blood were significantly higher in patients with
      clinically active sarcoidosis than in patients with inactive sarcoidosis or
      active tuberculosis and in normal subjects (active sarcoidosis: 18.9 +/- 17.2%,
      142 +/- 130.4 cells/microliters, n = 29; inactive sarcoidosis: 7.0 +/- 3.7%, 48.7
      +/- 35.0 cells/microliters, n = 16; active tuberculosis: 4.3 +/- 3.2%, 47.9 +/-
      36.6 cells/microliters, n = 19; control subjects: 5.0 +/- 1.9%, 77.6 +/- 37.7
      cells/microliters, n = 12). gamma delta T cells were significantly elevated in
      patients with sarcoidosis for 2 yr or more or those with Stage III radiographs.
      The level of gamma delta T cells, however, showed no correlation to the serum
      angiotensin-converting enzyme, a marker of active granuloma formation. gamma
      delta T cells were scarcely seen in bronchoalveolar lavages and in biopsy
      specimens, suggesting that these cells did not increase at the sites of
      inflammation. These findings suggest that increased levels of gamma delta T cells
      in the peripheral blood occur in active, long-term sarcoidosis, but that they are
      not directly related to granuloma formation.

PMID- 8143065
TI  - Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of
      interferon-gamma gene activation in pulmonary tuberculosis.
AB  - Mycobacterium-specific human helper T-cell clones produce a Th1 pattern of
      cytokines in vitro: interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), but
      little or no IL-4 or IL-5. To test the hypothesis that a similar Th1-like pattern
      of cytokine gene expression occurs in vivo in pulmonary tuberculosis we used in
      situ hybridization to detect cytokine mRNA expression by bronchoalveolar lavage
      cells from nine patients with microbiologically confirmed tuberculosis and nine
      control subjects. Because IFN-gamma may also originate from alveolar macrophages,
      simultaneous immunocytochemistry and in situ hybridization was applied to
      determine whether cytokine mRNA was localized to bronchoalveolar macrophages in
      addition to T-lymphocytes. When samples from patients with tuberculosis and
      control subjects were compared, there was a significant increase in numbers of
      IFN-gamma mRNA-positive BAL cells per 1,000 among patients with tuberculosis (p <
      0.01). Differences between the two groups in the proportions of cells expressing
      IL-2, IL-4, or IL-5 mRNA were not significant. Expression of IFN-gamma mRNA by
      macrophages was detected (median, 14.3% of IFN-gamma mRNA-positive BAL cells).
      However, the majority of IFN-gamma mRNA expressing BAL cells were T-lymphocytes
      (median, 80.7%). Activation of Th1-like bronchoalveolar T-lymphocytes, together
      with production of IFN-gamma by alveolar macrophages, may contribute to the local
      cellular immune response in pulmonary tuberculosis.

PMID- 8143066
TI  - Effect of glucocorticoids on collagen accumulation in pulmonary vascular
      remodeling in the rat.
AB  - Administration of corticosteroids may attenuate the development of pulmonary
      hypertension by inhibiting the cell proliferation and protein synthesis that
      occur in early pulmonary vascular remodeling. However, in vitro studies show that
      corticosteroids stimulate collagen synthesis in vascular smooth muscle cells, and
      corticosteroid administration may be deleterious in stimulating collagen
      deposition. To test whether corticosteroid treatment promotes vascular collagen
      production in vivo, we administered triamcinolone diacetate to rats exposed to
      10% O2 for 3 days and measured pro alpha 1(I) collagen mRNA and the
      hydroxyproline/protein ratio in the main pulmonary artery. Triamcinolone
      treatment (12 mg/kg intraperitoneally, once daily for 3 days) reduced mean right
      ventricular pressure (11 +/- 1 versus 14 +/- 1 mm Hg) and protein content of
      pulmonary arteries (1.8 +/- 0.1 versus 2.7 +/- 0.1 mg/vessel) (both p < 0.05).
      However, corticosteroid treatment produced a dose-related increase in pro alpha
      1(I) mRNA levels and increased the ratio of hydroxyproline/protein (47 +/- 2
      versus 38 +/- 3 micrograms/mg; p < 0.05). Thus, corticosteroid administration
      ameliorated the increase in pulmonary hypertension in early hypoxia, but
      increased the proportion of collagen in the vessel wall. Corticosteroid treatment
      in pulmonary vascular remodeling may be deleterious in increasing the
      concentration of collagen in the vessel wall.

PMID- 8143067
TI  - Recovery of motor skill following nervous system disorders: a behavioural
      emphasis.
AB  - Recovery of motor behaviour is, for a large part, the complex reintegration of
      sensory processes and motor output against the background of a decreasing
      cognitive involvement. Therefore, the measurement of motor output under simple
      and unperturbed conditions, isolated from these processes, reflects only a minor
      part of the recovery of skill. It is argued that there is an urgent need for
      procedures aimed at the objective study of behavioural recovery across time.
      Until now, these procedures have been lacking. This chapter provides a modest
      contribution to the development of these procedures.

PMID- 8143068
TI  - Mechanical methods of controlling ataxia.
AB  - Currently, the most effective and practical way of controlling ataxia which
      cannot be effectively treated with drugs, surgery or therapy is to use viscous
      damping. Devices are available commercially that have proved very effective in
      enabling people with ataxia to feed themselves and to use a computer, functions
      that they could otherwise not perform easily, if at all. For most people with
      severe ataxia this is very important. Being able to feed oneself is a very basic
      and important social and psychological function. Access to computers is extremely
      useful in this age, particularly for people with disabilities that prevent them
      from performing other functions. Provision of such devices can be one of the most
      effective ways of using resources to enrich the lives of people with ataxia.

PMID- 8143069
TI  - Towards a rational basis for physiotherapy in Parkinson's disease.

PMID- 8143070
TI  - Motor skill learning in cerebral palsy: movement, action and computer-enhanced
      therapy.
AB  - This chapter discusses the extent to which previous research into movement
      control can provide key principles on which to model therapy for individuals with
      severe cerebral palsy. It is suggested that the movement perspective has
      traditionally stressed the role of implicit knowledge of the dynamic
      characteristics of the body and that this provides support for the principles of
      biofeedback training. From a more ecological 'action' perspective, however, it is
      concluded that previous approaches to biofeedback have been too constrained and
      do not translate well to functional tasks. A variation of biofeedback training is
      proposed that provides real-time feedback to shape the subject's action, thereby
      guiding them through learning contexts that are moulded to fit the individual's
      capabilities. A pilot study of the efficacy of such an approach in adolescents
      with cerebral palsy is then presented. The potential of extending computer
      enhanced therapy into speculative areas such as virtual reality is also
      discussed.

PMID- 8143071
TI  - Pathogenesis of focal and segmental dystonias: implications for rehabilitation.

PMID- 8143072
TI  - Use of botulinum toxin in the treatment of cervical dystonia.
AB  - Idiopathic cervical dystonia, like other adult-onset focal dystonias, has been
      notoriously difficult to treat. Multiple approaches, including systemic drug
      treatment with anticholinergics, antidopaminergics, anticonvulsants, muscle
      relaxants and many other drugs as well as physiotherapy and psychotherapy,
      usually lead to only temporary amelioration in a minority of patients. Surgical
      selective EMG-controlled denervation of dystonic neck muscles produces better
      and, in the hands of some, lasting improvement. However, the procedure is
      invasive and as such less well accepted by patients. Local injections of
      botulinum toxin are strikingly successful in improving postural deviation and
      pain in about 80% of patients. They can be made on an outpatient basis and appear
      to be safe even over many repeat sessions. Dysphagia is potentially the most
      serious side-effect but can be decreased in incidence and severity by injecting
      lower doses, particularly into the sternomastoid. Major drawbacks at present are
      a lack of prospective data to establish optimal dosage and volume of injection
      guidelines to preserve good efficacy at a reduced risk of side-effects, and the
      need to continue indefinitely with repeat injections approximately every 3
      months.

PMID- 8143073
TI  - Physiotherapy for cerebral palsy: a historical review.
AB  - In view of the fact that brain damage cannot be reversed in cerebral palsy, it
      seems unlikely that there will be recovery other than maturation and compensatory
      movement. Therefore the two most important aims of treatment would appear to be
      to delay deformity and to promote the psychological well-being of the child
      within his or her own family unit. To facilitate these aims research needs to be
      undertaken by clinical scientists to assess the relative merits of the various
      approaches. Research methodologies used in psychology and the social sciences may
      well prove to be more useful for this purpose than those used in traditional
      medical research. To quote Harris (1989): 'Every discipline evolves its methods
      in response to the needs of the time and through the genius of its individual
      practitioners and we will learn how best to combine descriptive research with
      quantitative methods, with experiment and with techniques not yet invented'.

PMID- 8143074
TI  - Local treatment of spasticity.

PMID- 8143075
TI  - Intrathecal baclofen.
AB  - The intrathecal application of the GABA-B agonist baclofen has become more and
      more popular for severe spinal spasticity. Since it was first introduced in 1984
      more than 1000 patients worldwide have been treated by this method, using an
      implantable drug administration device. Clinical data from 48 patients are
      presented, as well as further experience from a multicentre trial conducted in
      Europe, in conjunction with a literature overview. The method is now generally
      accepted as a powerful treatment for spasticity due to spinal lesions of whatever
      aetiology; improvement in mobility and function as well as relief of spastic pain
      are the most obvious benefits for the patient. Bladder function is improved in
      terms of increased bladder volume and lowered residual volume. In patients with
      supraspinal lesions causing muscle hypertension, where several mechanisms usually
      contribute besides hyper-reflexia (spasticity), the response has been less
      pronounced, but intrathecal baclofen still seems to have clinical effects that
      are superior to those of any oral drug treatment. The initial technical and
      methodical problems have been solved and today the procedure is generally
      assessed as safe.

PMID- 8143076
TI  - Retaining and retraining balance after stroke.

PMID- 8143077
TI  - Utilization of an antibody specific for human dystrophin to follow myoblast
      transplantation in nude mice.
AB  - Human myoblasts were transplanted in nude mice. The efficacy of these
      transplantations was analyzed using a monoclonal antibody (NCLDys3) specific for
      human dystrophin. This antibody did not reveal any dystrophin in nude mice that
      did not receive a human myoblast transplantation. However, about 30 days after a
      human myoblast transplantation, dystrophin-positive muscle fibers were observed.
      They were not abundant, and were present either in small clusters or isolated.
      This technique follows the fate of myoblast transplantation in animals that
      already have dystrophin, and distinguishes between new dystrophin-positive fibers
      due to the transplantation and the revertant fibers in mdx mice. Moreover, this
      technique does not require any labelling of the myoblasts before transplantation.
      It can also be used to detect dystrophin produced following the fusion of
      myoblasts transfected with the human dystrophin gene.

PMID- 8143078
TI  - Islet cell mass and the longevity of islet grafts in diabetic rats.
AB  - In an attempt to demonstrate that a limited beta-cell mass is able to maintain
      normoglycemia in streptozocin-diabetic rats, two groups of inbred rats received
      transplants of 500 or 1000 neonatal islets (corresponding to 10 and 20% of total
      islet cell mass, respectively) into the spleen. A close correlation was found
      between the functional longevity of the islet graft, and the total beta-cell mass
      transplanted into the diabetic animals. Although euglycemia was maintained for 4
      12 mo, the islet transplants were insufficient to produce glucose tolerance tests
      equal to those observed in normal rats. Relapse of diabetes correlated with
      histological findings of distorted islet architecture containing vacuolated beta
      cells in the grafts. This condition was not reversed after a month of
      normoglycemia. Spontaneous recovery of beta-cell function in native islets was
      documented in 50% of the diabetic rats with prolonged normoglycemia following
      islet transplantation. This report shows that transplantation of as few as 500
      neonatal islets, the equivalent of 10% of total islet cell mass, is sufficient to
      maintain normoglycemia in diabetic rats, albeit temporarily. A close correlation
      was found between the transplanted islet cell mass and the functional longevity
      of the islet graft.

PMID- 8143079
TI  - Sertoli cell-enriched fractions in successful islet cell transplantation.
AB  - Prolonged survival of Islet- allo- and xenografts can be induced following
      implantation of the islets into the abdominal testis of diabetic rats. We
      previously showed that a factor released by Sertoli cells appears to be
      responsible for the protection of the intratesticular islet allo- and xenografts
      against rejection. The aim of this study was to examine whether an
      immunologically privileged site can be established in an organ site in vivo,
      other than the testis, such as the renal, subcapsular space, to make feasible the
      grafting of female recipients as well. A total of 36 male and 21 female,
      diabetic, PVG rats were divided into six different treatment groups: 1) Six male
      rats were grafted with islets from Sprague-Dawley (S-D) donor rats only. 2) Ten
      male rats were grafted with islets from (S-D) donors and were then given a short
      course of cyclosporine (CsA) posttransplantation. 3) Ten male rats were grafted
      with islets from (S-D) donors and with Sertoli cell-enriched fractions (SEF) from
      PVG donors but without CsA. 4) Ten male rats were grafted with a combination of
      islets from (S-D) and SEF from (PVG), donors, respectively, and CsA. 5) Ten
      female rats were given an identical combination of cells and CsA as depicted for
      group 5. 6) Ten female rats were grafted with a combination of islets and SEF,
      both cell types from S-D donors, and CsA. The results showed that 70% to 100% of
      the grafted rats in groups 1, 2, and 3 remained hyperglycemic.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8143080
TI  - In vitro labeling strategies for identifying primary neural tissue and a neuronal
      cell line after transplantation in the CNS.
AB  - Potential labels for identifying embryonic raphe neurons and a clonal, neuronally
      differentiating, raphe-derived cell line, RN33B, in CNS transplantation studies
      were tested by first characterizing the labels in vitro. The labels that were
      tested included 4',6-diamidino-2-phenylindole hydrochloride, 1,1'-dioctadecyl
      3,3,3'-tetramethylindocarbocyanine perchlorate, the Escherichia coli lacZ gene,
      Fast Blue, Fluoro-Gold, fluorescein-conjugated latex microspheres, fluorescein
      isothiocyanate-conjugated or nonconjugated Phaseolus vulgaris leucoagglutinin,
      methyl o-(6-amino-3'-imino-3H-xanthen-9-yl) benzoate monohydrochloride, or
      tetanus toxin C fragment. Subsequently, the optimal in vitro labels for embryonic
      raphe neurons and for RN33B cells were characterized in vivo after CNS
      transplantation. In vitro, 1,1'-dioctadecyl-3,3,3'-tetramethylindocarbocyanine
      perchlorate (DiI) optimally labeled embryonic neurons. The Escherichia coli lacZ
      gene optimally labeled RN33B cells. Most labels were rapidly diluted in cultures
      of embryonic astrocytes and proliferating RN33B cells. Some labels were toxic and
      were often retained in cellular debris. In vivo, DiI was visualized in
      transplanted, DiI-labeled raphe neurons, but not in astrocytes up to 1 mo
      posttransplant. DiI-labeled host cells were seen after transplantation of lysed,
      DiI-labeled cells. beta-Galactosidase was visualized in transplanted, Escherichia
      coli lacZ gene-labeled RN33B cells after 15 days in vivo. No beta-galactosidase
      was seen in host cells after transplantation of lysed, lacZ-labeled RN33B cells.
      The results demonstrate that labels for use in CNS transplantation studies should
      be optimized for the specific population of donor cells under study, with the
      initial step being characterization in vitro followed by in vivo analysis.
      Appropriate controls for false-positive labeling of host cells should always be
      assessed.

PMID- 8143081
TI  - Two PC12 pheochromocytoma lines sealed in hollow fiber-based capsules tonically
      release L-dopa in vitro.
AB  - Two PC12 cell-derived lines have been studied following encapsulation into
      polymer-based hollow fibers with respect to secreted catecholamines and their
      metabolites. Cellular encapsulation provides a chronic microperfusion environment
      within which basally secreted PC12 products can be readily measured. Encapsulated
      PC12 cells grown and held under the conditions specified in this report basally
      release amounts exceeding their total cellular stores of the dopamine precursor L
      DOPA and the electrochemically active dopamine metabolites DOPAC and HVA during
      45-min static incubations. Under these same conditions, these cells release less
      than 0.1% of their total cellular store of dopamine. Depolarizing incubations
      enhance dopamine secretion eightyfold and enhance secretion of L-DOPA, HVA, and
      DOPAC about twofold. The relative composition of products basally secreted
      differs between PC12-derived cell lines, and an inverse relationship exists
      between basal release of L-DOPA and total cellular store of dopamine. These
      results further indicate that selected PC12 cell lines are potentially a source
      of both dopamine and L-DOPA in therapeutic cellular replacement applications.

PMID- 8143082
TI  - Metabolic activity and proliferation of CHO cells in hydroxyethyl methacrylate
      methyl methacrylate (HEMA-MMA) microcapsules.
AB  - To better understand encapsulated cell behaviour, Chinese Hamster Ovary (CHO)
      fibroblasts were encapsulated in HEMA-MMA microcapsules and short-term (<2 wks)
      proliferation and changes in metabolic activity were investigated in vitro. CHO
      cells were observed to undergo rapid proliferation in the first week following
      encapsulation after which a growth arrest was obtained at approximately 3500
      cells/capsule. The cell growth was localized in aggregates in the capsule core,
      resulting in high local cell density but low cell density in the whole capsule
      interior (approximately 10(7) cells/mL). The total metabolic activity, as
      determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium)
      assay, within the microcapsules increased in the first week, with no significant
      change afterwards. A broad variation in metabolic activity among the individual
      capsules was obtained. Supplementing the cell suspension with 20% Ficoll 400
      during the encapsulation process resulted in significantly higher morphological
      uniformity among the individual capsules (with reduced capsule wall thickness and
      eccentricity); however, this did not change the extent of heterogeneity in
      metabolic activity. We conclude that viability and proliferation ability (at
      least to a limited extent) of CHO cells are maintained in HEMA-MMA microcapsules.
      The local cell growth and subsequent growth arrest remain issues to be addressed
      in order to obtain better utilization of the microcapsule core volume.
      Alternatively, small diameter (< 400 microns as opposed to the present
      approximately 750 microns diameter) capsules are necessary.

PMID- 8143083
TI  - Results of a triple blind clinical study of myoblast transplantations without
      immunosuppressive treatment in young boys with Duchenne muscular dystrophy.
AB  - The effects of myoblast transplantations without an immunosuppressive treatment
      on muscle strength, and the formation of dystrophin-positive fibers was studied
      in five young boys with Duchenne muscular dystrophy (DMD) using a triple blind
      design. Injections of myoblasts were made into one biceps brachii (BB), and the
      opposite BB, used as a control, was sham-injected; the experimenters and the
      patient were blind to the myoblast-injected side. At the same time, myoblasts
      were also injected in the left tibialis anterior (TA) of these patients. The
      strength developed during maximal static contractions of the elbow flexor and
      extensor muscles was measured with a Kin-Com dynamometer. No increase in static
      elbow flexion torque was measured at any time from 2 mo up to 18 mo after the
      transplantation. One month after the transplantation, the percentage of
      dystrophin-positive fibers in the myoblast-injected TA ranged from 0 to 36%,
      while it ranged from 0 to 4% on the control side. The expression of dystrophin in
      these fibers, however, was generally low, and most likely less than 10% of the
      normal level. In the biceps brachii of both sides 6 mo after the transplantation,
      less than 1.5% of dystrophin-positive fibers were detected. The injections also
      triggered a humoral immune response of the host. Antibodies were capable of
      fixing the complement, and of lysing the newly formed myotubes. One of the
      antigens recognized by this immune response is possibly dystrophin. These results
      strongly suggest that myoblast transplantations, as well as gene therapy for DMD,
      cannot be done without immunosuppression.

PMID- 8143084
TI  - Segregation of holocentric chromosomes at meiosis in the nematode, Caenorhabditis
      elegans.
AB  - The meiotic segregation of the holocentric chromosomes of Caenorhabditis elegans
      in both spermatogenesis and oogenesis is described. The extended kinetochore
      typical of the mitotic chromosome could not be differentiated on meiotic
      bivalents; instead microtubules appeared to project into the chromatin. The
      meiotic spindles formed during spermatogenesis contain centrioles and asters,
      while in oogenesis the spindles are acentriolar and barrel shaped. The formation
      of the acentriolar spindle was studied in fixed specimens by anti-tubulin
      immunofluorescence. Microtubule arrays were seen first to accumulate in the
      vicinity of the meiotic chromosomes prior to congression. At later stages,
      elongated spindle structures up to 13 mu in length were observed parallel to the
      surface of the embryo. Further development of the spindle appeared to involve its
      shortening into a barrel shape and rotation so that one spindle pole was opposed
      to the membrane. By anaphase the pole-to-pole spindle length reached a minimum of
      3-4 mu. One end of each chromatid in the meiotic bivalent was labelled by in situ
      hybridization of a probe DNA to show that in oogenesis the chromatids were
      associated end-to-end in the bivalent. Furthermore, either the right or the left
      ends of the homologues could be held in association. At metaphase I the bivalents
      were oriented axially, such that kinetic activity was restricted to one end of
      each pair of sister chromatids. At metaphase II the chromosomes were also aligned
      axially.

PMID- 8143085
TI  - A protein homologous to human Ku p70-protein is required for reconstitution of
      Xenopus sperm pronuclei.
AB  - The monoclonal antibody mAbH6, which recognizes one human Ku-protein (p70), cross
      reacted with the counterpart protein from Xenopus eggs. The Xenopus antigen
      purified with a mAbH6-Sepharose column was a complex of 88 kDa and 72 kDa
      proteins. The role of Ku protein in nuclear structure formation was studied using
      a cell-free nuclear assembly extract derived from Xenopus interphase eggs. The
      protein was distributed on the surface of demembranated sperm chromatin and in
      the membrane vesicle fraction of the nuclear assembly extract. Addition of mAbH6
      to the assembly extracts prevented the completion of reconstitution of pronuclei
      from demembranated sperm chromatins, although partial decondensation mediated by
      nucleoplasmin was not impeded. As a result, the sperm chromatin remained in
      partially swollen structures or formed round but small anomalous nuclei. Nuclear
      membranes were formed on the nuclei in mAbH6-inhibited extract systems, but DNA
      synthesis was largely decreased, suggesting the incomplete reconstitution of
      pronuclei. The incorporation of lamin to the nuclei was inhibited by mAbH6. It is
      suggested that the Xenopus Ku-homologous protein has a role in the formation of
      the lamin layer after nuclear membrane reconstitution.

PMID- 8143086
TI  - Meiotic synapsis of homogeneously staining regions (HSRs) in chromosome 1 of Mus
      musculus.
AB  - About 50 copies of a long-range repeat DNA family with a repeat size of roughly
      100 kb and with sequence homology to mRNAs are clustered in the G-light band D of
      chromosome 1 of the house mouse, Mus musculus. We studied amplified versions of
      the cluster which are found in many wild populations of M. musculus. They are
      cytogenetically conspicuous as one or two C-band positive homogeneously staining
      regions (single- and double band HSRs) which increase the mitotic length of
      chromosome 1. The double band HSR was phylogenetically derived from a single band
      HSR by a paracentric inversion. In homozygous condition, such HSRs contribute,
      albeit not as much as expected from their mitotic length, to the synaptonemal
      complex (SC) length of chromosome 1. In HSR heterozygous animals an elongation of
      the SCs was not noticeable. In single band HSR heterozygous males, synapsis
      proceeds regularly and continuously from the distal telomere towards the
      centromeric end without forming buckles. Thus, the single band HSR has no adverse
      effect on pairing. The same straight pairing behaviour was found in the majority
      of double band HSR heterozygous spermatocytes. This shows that extensive
      nonhomologous pairing can take place in the earliest phase of synapsis. Synapsis
      was discontinuous, leaving the central part of the bivalent 1 asynapsed, in only
      14.3% of double band HSR heterozygous cells. In such cells the chromosome 1 SC is
      completed at a later stage of meiosis. The delay is presumably an effect of the
      inversion that includes one HSR band and the segment between the two HSR bands.

PMID- 8143087
TI  - Direct detection of repetitive, whole chromosome paint and telomere DNA probes by
      immunogold electron microscopy.
AB  - Biotinylated repetitive, whole chromosome paint and telomere DNA probes were
      investigated at the electron microscope level after non-isotopic in situ
      hybridization and direct immunogold detection. The protocol described allowed the
      visualization of a biotinylated chromosome 1 specific satellite DNA probe in the
      light microscope without silver intensification. This sensitive method was
      exploited to analyse factors contributing to signal strength in immunogold
      chromosome painting. Furthermore, it allowed us to investigate the distribution
      of (TTAGGG)n telomere repeats in human metaphase chromosomes and interphase
      nuclei. Telomeric and internal (TTAGGG)n repeats were detected at high spatial
      resolution in human metaphase chromosomes. In the periphery of lymphocyte
      interphase nuclei, two types of telomere hybridization signals were observed.
      They differed remarkably in compactness, indicating two types of chromatin
      conformation present at the interphase telomeres in situ.

PMID- 8143088
TI  - Chromosome research--look forward to 2001.

PMID- 8143089
TI  - Aneuploidy, structural chromosome changes, and DNA amounts in the annual taxa of
      the Haplopappus spinulosus complex.
AB  - Haplopappus gracilis (n = 2), Haplopappus ravenii (n = 4), and Haplopappus
      wigginsii (n = 4) are isolated by F1 hybrid sterility due mainly to translocation
      heterozygosity. There is no evidence that this can be overcome at the diploid
      level so that introgression can occur among them. They are also separated
      geographically, but occasional populations of H. gracilis and H. ravenii may be
      brought together along roadways to form sterile hybrids. There were no
      statistically significant differences in nuclear DNA content among the same or
      structurally different aneuploid n = 2 and n = 3 chromosome races or ecotypes of
      H. gracilis. Some of the H. gracilis races were not significantly different from
      one race of the ancestral H. ravenii, and these samples of both species were from
      plants growing on poor soils in contrast to accessions from normal habitats. How
      much and which classes of DNA in these species are subject to changes induced by
      environmental effects is not known. There were no correlations between DNA
      amounts and altitude, latitude, and longitude. H. wigginsii had a greater amount
      of DNA per nucleus than either H. ravenii or H. gracilis, and its increased DNA
      content may reflect a more rapid accumulation of noncoding sequences due to
      facultative self-compatibility not found in the other two species.

PMID- 8143090
TI  - Multi-chromosomal location of ribosomal RNA genes and heterochromatin association
      in brown trout.
AB  - The ribosomal rRNA genes have been mapped by fluorescent in situ hybridization
      (FISH) to brown trout chromosomes. One major NOR chromosome pair and 8 novel
      minor NOR chromosome pairs have been found. Both major and minor NORs were
      closely related to polymorphic heterochromatin, as revealed by FISH and C
      banding. These results are discussed with respect to NOR expression, the
      relationship between rDNA and heterochromatin, and evolutionary aspects.

PMID- 8143091
TI  - Inverted and satellited Y chromosome in the orangutan (Pongo pygmaeus).
AB  - An inverted and satellited Y chromosome of almost acrocentric appearance was
      detected in seven of 14 male orangutans. In the remaining seven animals a
      submetacentric Y chromosome without NORs occurred. The high frequency with which
      the satellited Y chromosomes were associated with acrocentric autosomes and the
      positive AgNO3-staining of their satellite stalks clearly indicate the active
      state of the NOR on the Y chromosomes. DNA fingerprinting in two orangutan
      families showed that the inverted and satellited Y chromosomes in carrier
      orangutan males do not interfere with normal fertility. Within our sample of male
      orangutans studied, the inverted and satellited Y chromosome is restricted to
      Sumatran animals; all Bornean specimens possessed the submetacentric Y
      chromosome. The question arises whether these two kinds of Y chromosome differ
      constitutively between the Pongo pygmaeus subpopulations.

PMID- 8143092
TI  - Organization and molecular cytogenetics of a satellite DNA family from Hoplias
      malabaricus (Pisces, Erythrinidae).
AB  - The chromosomes of the primitive South American teleost fish Hoplias malabaricus
      have been analyzed by classical cytogenetic (C-, AgNOR-, Hoechst 33258-, and Q
      banding) techniques. A highly repetitive DNA family has been cloned and
      sequenced. It is a tandemly repeated sequence of about 355 bp, yielding an
      overall base pair composition of 67% AT with long runs of > 50% As and 70% Ts.
      Analysis of sequence variation has allowed the further categorization of Hoplias
      satellite DNA into two evolutionary related subfamilies A and B, distinguishable
      by characteristic insertions and deletions within this 355-bp monomer. Subfamily
      A satellite is found (in diverged form) at the centromeres of most H. malabaricus
      chromosomes. Sequence variants are clustered on specific chromosomal subsets.
      Subfamily B satellite is highly specific for the paracentromeric heterochromatin
      on one particular chromosome pair by fluorescence in situ hybridization. These
      results indicate that the Hoplias satellite DNA family has evolved in a concerted
      manner predominantly via recombination events involving homologous, rather than
      non-homologous chromosome regions. The clones isolated here may be useful for the
      molecular, genetic, and cytological analysis of the genus Hoplias.

PMID- 8143093
TI  - Scanning electron microscopy of synaptonemal complexes.
AB  - The novel application of scanning electron microscopy to study whole-mount
      surface-spread synaptonemal complex complements of rye (Secale cereale) and rat
      (Rattus norvegicus) is described. Scanning electron microscopy is able to resolve
      the third dimension in such preparations and improve the tracing of the
      continuity of lateral elements without losing information that could be obtained
      by conventional transmission electron microscopy. This improvement is likely to
      benefit detailed studies of chromosome synapsis and karyology, and may provide a
      means of circumventing technical obstacles inhibiting the use of surface-spreads
      as substrates for in situ hybridization under the electron microscope.

PMID- 8143094
TI  - Localization of seed protein genes on flow-sorted field bean chromosomes.
AB  - Chromosomes from reconstructed field bean (Vicia faba L.) karyotypes were flow
      sorted and the DNA was used for the physical localization of seed storage and
      nonstorage (USP) protein genes using PCR with sequence specific primers. The data
      were confirmed and refined by using DNA of microisolated chromosomes of other
      karyotypes as the target for PCR. The specificity of the PCR products was proved
      by restrictase digestion into fragments of predicted length or by reamplification
      using 'nested' primers. The genes are located within defined regions of
      chromosome I (USP = unknown seed protein genes), II (vicilin genes, legumin B3
      genes), III (legumin B4 genes), IV (pseudogenes psi 1) and V (legumin A genes and
      pseudogenes psi 1). Except for the pseudogene derived from the sequence of
      legumin B4 gene, all members of each gene family are located in one chromosome
      region exclusively. This approach proved to be useful for localizing genes that
      cannot be mapped genetically (due to the lack of allelic variants) and might be
      applied to integrate physical and genetic maps.

PMID- 8143095
TI  - Comparative mapping of SRY in the great apes.
AB  - Cytogenetic studies of the primate Y chromosomes have suggested that extensive
      rearrangements have occurred during evolution of the great apes. We have used in
      situ hybridization to define these rearrangements at the molecular level. pHU-14,
      a probe including sequences from the sex determining gene SRY, hybridizes close
      to the early replicating pseudoautosomal segment in a telomeric or subtelomeric
      position of the Y chromosomes of all great apes. The low copy repeat detected by
      the probe Fr35-II is obviously included in Y chromosomal rearrangements during
      hominid evolution. These results, combined with previous studies, suggest that
      the Y chromosome in great apes has a conserved region including the
      pseudoautosomal region and the testis-determining region. The rest of the Y
      chromosome has undergone several rearrangements in the different great apes.

PMID- 8143097
TI  - Hypercalcaemia: historical perspectives and present management.
AB  - Hypercalcaemia is a well-recognised complication in patients with several types
      of cancer. Since determination of the serum calcium has become routine
      particularly in hospital patients, the identification of hypercalcaemia
      associated with cancer has increased. Cancer is the most common cause of
      hypercalcaemia arising in hospitalised patients, and overall approximately one
      third of all patients presenting with hypercalcaemia have an underlying cancer.
      In Western countries, the common causes of hypercalcaemia are cancers of the lung
      and breast. The median survival of patients with hypercalcaemia and cancer is
      only 5 weeks, indicating that in many patients treating hypercalcaemia may not
      achieve prolonged survival, even if symptoms are palliated. The clinical
      presentations of hypercalcaemia are well known, encompassing gastrointestinal,
      neurological, cardiovascular and renal symptoms. Management approaches have
      evolved over the past few years from hydration and use of drugs that promote
      calcium excretion to new treatments that inhibit bone resorption.

PMID- 8143096
TI  - Evidence for a nuclear compartment of transcription and splicing located at
      chromosome domain boundaries.
AB  - The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome
      domains in various mammalian cell types are described. The visualization of
      splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed
      distinctly different distribution patterns in these cell types. Heat shock
      experiments confirmed that the distribution patterns also depend on physiological
      parameters. Using a combination of fluorescence in situ hybridization and
      immunodetection protocols, individual chromosome domains were visualized
      simultaneously with the Sm antigen or the transcript of an integrated human
      papilloma virus genome. Three-dimensional analysis of fluorescence-stained target
      regions was performed by confocal laser scanning microscopy. RNA transcripts and
      components of the splicing machinery were found to be generally excluded from the
      interior of the territories occupied by the individual chromosomes. Based on
      these findings we present a model for the functional compartmentalization of the
      cell nucleus. According to this model the space between chromosome domains,
      including the surface areas of these domains, defines a three-dimensional network
      like compartment, termed the interchromosome domain (ICD) compartment, in which
      transcription and splicing of mRNA occurs.

PMID- 8143098
TI  - Medical treatment of tumor-induced hypercalcemia and tumor-induced osteolysis:
      challenges for future research.
AB  - Tumor-induced hypercalcemia (TIH) and tumor-induced osteolysis (TIO) are
      essentially due to a marked increase in osteoclast-mediated bone resorption.
      Parathyroid-hormone-like protein plays an essential role in TIH, and maybe in
      TIO, but other substances, such as growth factors or cytokines, could contribute
      to the osteoclast activation and osteoblast inhibition secondary to the
      neoplastic infiltration of the skeleton. Treatment of TIH essentially consists of
      volume repletion and administration of potent anti-osteolytic drugs. Intravenous
      administration of the bisphosphonate clodronate or pamidronate is particularly
      useful for this. Pamidronate at a dose of 1.0-1.5 mg/kg as a single 4- to 24-h
      infusion can normalize serum calcium in about 90% of hypercalcemic cancer
      patients. The apparently low response rate of bone metastases to systemic
      antineoplastic therapy seems essentially to reflect the relative insensitivity of
      our current methods for assessing response in TIO. Quantitative evaluation of
      pain and of newly developed biochemical markers of bone turnover could be
      particularly useful for early assessment of response. Prolonged administration of
      oral pamidronate could reduce by almost one-half the complications of TIO, and
      iterative bisphosphonate infusions could induce a dramatic relief of bone pain in
      one-third and a sclerosis of lytic lesions in one-fourth of the cases. These data
      must, however, be confirmed in randomized blind trials and many questions remain
      unanswered concerning the optimal therapeutic schemes. Despite these limitations,
      medical therapy of TIO by non-cytotoxic means has already become a reality.

PMID- 8143099
TI  - Prospective multicentric study of the etiology of 1051 bacteremic episodes in 782
      cancer patients. CEMIC (French-Belgian Study Club of Infectious Diseases in
      Cancer).
AB  - A total of 1051 bacteremic episodes (782 patients) were prospectively recorded in
      10 cancer centers (9 French, 1 Belgian), with: patient's age (mean 53, range 1-89
      years), underlying cancer, neutropenia (< 1000 neutrophils/microliters; 233),
      signs and symptoms, type of i.v. line (percutaneous central: 534; peripheral:
      228; central implanted: 304), treatment, blood culture system, number of positive
      blood culture bottles/total obtained, time to growth. Of all episodes, 23.2%
      occurred within 48 h of admission. The patients were receiving systemic
      antibiotics at sampling (on AB) in 34.6% of cases. The 1147 pathogens isolated
      (86 polymicrobial) were: E. coli (10.7%), Klebsiella-Enterobacter-Serratia
      (6.1%), other enterobacteriaceae (2.2%), Pseudomonas aeruginosa (4.8%), other
      nonfermenters (4.7%), coagulase-negative staphylococci (CNS, 40.8%),
      Staphylococcus aureus (9.9%), streptococci (5.4%), enterococci (2.2%), anaerobes
      (3.4%), yeasts (3.5%), and other bacteria (6.9%). The CDC (Centers for Disease
      Control) criteria (1988) were used to assess significance: group 1: pathogenic
      species (616 episodes; 59%); group 2: clinical signs and isolation of a
      "contaminant" species (47; 4.5%); group 3: as in group 2 with an i.v. line and
      empiric antibiotic treatment (181 episodes including 176 CNS; 17%); group 4: non
      significant (207 episodes including 203 CNS; 20%). Groups 1-3, in which the
      episodes were considered to be significant (844 episodes; 80%) were compared with
      non-significant episodes (Fisher). Significant differences (P < or = 0.05) were
      seen in time to growth (median growth within 24 h vs 48 h), fever (86% vs 54%),
      chills (40% vs 3%), hypotension (10% vs 2%), septic shock (9% vs 1%),
      polymicrobial etiology (10% vs 0.5%), and initiation of empiric antibiotic
      treatment (71% vs 4%). Bacteremic episodes of CDC groups 1, 3 and 4 were further
      studied in episodes with a single isolate as a doubtful clinical significance
      (482 episodes) and episodes with > or = 2 bottles positive of probable clinical
      significance (569 episodes; 54%). In group 1 (218 doubtful, 398 probably
      significant episodes) significant differences were seen in chills (36% vs 52%),
      shock (7% vs 13%), polymicrobial (8% vs 17%), initiation of empiric antibiotic
      treatment (60% vs 72%); in group 3 (87 doubtful, 94 probably significant) in time
      to growth delay; in group 4 (177 doubtful, 30 probably significant) in proportion
      with implanted catheter (26% vs 52%), fever (62% vs 10%), and time to growth.
      This study confirms the predominant role of Gram-positive cocci in bacteremia
      occurring in cancer patients.

PMID- 8143101
TI  - Role of support groups in cancer care.
AB  - Support groups have been introduced in medicine since a number of years and
      several studies indicate that these groups can be beneficial for cancer patients.
      This article reviews the concept and types of support groups in cancer care. The
      demands on facilitators and patients in these groups are discussed and potential
      problems are emphasized. Ground rules for the establishment of a successful
      support group for cancer patients are described.

PMID- 8143100
TI  - Gram-negative bacteremia.
AB  - In the 1960s, almost all patients who developed gram-negative bacteremia during
      granulocytopenia died; death occurred before blood culture results were available
      in about 50% of cases; many patients received antibiotics that were, at best,
      suboptimal and frequently inactive against the invading pathogen. In the early
      1970s epidemiological studies demonstrated that more than 50% of gram-negative
      bacteremias were caused by hospital-acquired strains which colonized along the
      alimentary canal and caused infection in a limited number of locations,
      especially the pharynx, lungs, colon, and perianum. Surveillance culture studies
      have demonstrated that among acquired gram-negative bacilli, Pseudomonas
      aeruginosa will almost invariably proceed to bacteremia if the patient becomes
      profoundly neutropenic, with Escherichia coli and Klebsiella pneumoniae leading
      to bacteremia in only a moderate number of patients and other gram-negative
      bacilli rarely progressing to bacteremia despite colonization. Hence, the leading
      causes of bacteremia in the granulocytopenic patient are E. coli, K. pneumoniae
      and P. aeruginosa. Further investigations demonstrated that gram-negative bacilli
      were acquired from hands, food, and water, thus leading to approaches to
      infection prevention which included careful handwashing, low-microbial-content
      diet, and attention to water sources, including ice machines. Another basic
      approach to infection prevention has been to suppress gram-negative bacilli
      colonizing the alimentary canal with oral nonabsorbable antibiotics or, more
      recently and more effectively, with agents such as the fluoroquinolones which,
      unlike previous regimens, do not concurrently suppress the anaerobic flora, hence
      maintaining colonization resistance. The third basic approach to infection
      prevention is to improve the host defense factors, principally by a more rapid
      return of circulating granulocytes with the use of colony-stimulating factors
      such as granulocyte/macrophage colony-stimulating factor or granulocyte colony
      stimulating factor. As to therapy, the fundamental approach with presumed gram
      negative bacteremia is the prompt institution of empiric antibiotic therapy when
      fever first develops in the setting of granulocytopenia. There is a short "window
      of opportunity" after which no therapy will be effective. Combinations of
      antibiotics such as a beta-lactam and an aminoglycoside are used for multiple
      reasons: to afford coverage in the event the pathogen, proves resistant to one of
      the agents, to afford a synergistic activity thus improving and prolonging the
      serum bactericidal activity, and to reduce the development of resistance.
      However, patients can be divided into two risk groups: those with
      granulocytopenia and a regenerating bone marrow and those with an aplastic marrow
      who will have persistent, profound (< 100 microliters) granulocytopenia.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8143102
TI  - Preliminary results of a study assessing asthenia and related psychological and
      biological phenomena in patients with advanced cancer.
AB  - Asthenia is a very common symptom of patients with advanced cancer, but its
      investigation is hindered by a lack of suitable validated measuring instruments.
      The goal of the present study was to construct and validate a questionnaire for
      the study of asthenia in cancer patients, as well as to establish correlations
      with other symptoms and physiological and biochemical parameters. A group of 31
      patients with advanced cancer and a control group of 30 healthy volunteers were
      examined. The proposed questionnaire, based on visual analogue scales, questions
      with categorical answers and on the hospital anxiety and depression scale was
      validated by comparing results of the patient and control groups, by the
      test/retest method and by comparison with the evaluation of an observer.
      Correlation with various physiological and biochemical parameters was performed.
      The questionnaire distinguished well among the patients and control groups. VAS
      of asthenia proved quite stable over a period of 5 days. Correlations of asthenia
      with lack of appetite, the hospital anxiety and depression scale, weight, heart
      rate and serum cortisol levels could be established. No significant correlation
      between asthenia and various serum markers of inflammation and cytokines,
      including C-reactive protein, tumour necrosis factor, interleukin-1, and
      interleukin-2 receptors, could be found. The proposed questionnaire for
      evaluation of asthenia could be validated in a patient sample of limited size and
      a simplified questionnaire based on visual analogue scales is being developed for
      further investigations.

PMID- 8143103
TI  - Implantable subcutaneous infusion ports.
AB  - Limited vascular access hinders administration of chemotherapy, blood products
      and antibiotics in cancer patients. Repeated venous cannulation is often
      psychologically traumatic to patients. The use of a subcutaneous infusion port
      allows convenient vascular access. Twenty-two cancer patients had ports implanted
      for venous access (17 patients) and administration of regional chemotherapy (5
      patients). The period of indwelling ranged from 70 to 470 days (median 270 days).
      Two patients (9%) had wound dehiscence that required port revision. Despite this,
      the wound did not heal in 1 patient and the port had to be removed. Other
      complications included venous thrombosis (5%) and subcutaneous haematoma (5%).
      There was no catheter-related bacteraemia. The subcutaneous infusion port
      provides a suitable vascular access in cancer patients.

PMID- 8143104
TI  - Cancer pain assessment and treatment curriculum guidelines. Ad Hoc Committee on
      Cancer Pain of the American Society of Clinical Oncology.
AB  - More than 70% of patients with cancer develop significant pain at some time
      during their illness. Despite the general consensus that most cancer pain can be
      treated effectively, many patients receive inadequate treatment of their pain.
      One significant contributing factor is the failure of health care professionals
      to receive formal training in this important aspect of oncology. The "Cancer Pain
      Assessment and Treatment Curriculum Guidelines" reflect the American Society of
      Clinical Oncology's commitment to providing optimal pain relief to patients with
      cancer. These guidelines represent an effort to promote formal instruction on the
      assessment and treatment of cancer pain in training programs and continuing
      education courses. The curriculum is broad in scope and applicable to patients of
      all ages. The guidelines emphasize the need for (1) routine pain assessment, (2)
      proficiency in prescribing opioids, nonopioid analgesics, and adjuvant
      medications, and (3) an understanding of the potential benefits of
      antineoplastic, anesthetic, neurosurgical, and behavioral approaches, which often
      require a coordinated multidisciplinary approach. The curriculum should prove a
      valuable guide to those who wish further education on the optimal treatment of
      cancer pain.

PMID- 8143106
TI  - The information to the cancer patient: psychosocial and spiritual implications.
AB  - The issue of whether, how and how much to tell cancer patients about their
      diagnosis and prognosis is confronted in different ways in different countries.
      This paper reflects my direct experience as a medical oncologist both in the US
      and in Italy. It is an attempt to describe two different ways of dealing with
      truth-telling in oncology and to explore their reasons and consequences.

PMID- 8143105
TI  - Pain management: physiopathology, future research and endpoints.
AB  - In this article, first, the different stages of acquisition and processing of
      nociceptive information from peripheral receptor to brain are reviewed and the
      plastic changes that accompany tissue injury are underlined. For instance, the
      subclassification of peripheral receptors in nociceptors and non-nociceptors
      (e.g., mechanoreceptors, thermoreceptors) must be understood in the light of
      peripheral sensitization. This phenomenon is the probable explanation for primary
      hyperalgesia, the decrease in pain threshold at the site of injury. The
      observation that substance P enhances N-methyl-D-aspartate (NMDA)-elicited
      responses suggests that these two receptors may operate in concert to prolong and
      amplify the afferent input generated by peripheral tissue injury. Such afferent
      barrage induces a state of central sensitization. Second, the major problems in
      the management of cancer pain, i.e. the development of tolerance to opioids and
      opioid-insensitive pain, are discussed. The loss of drug effect observed after
      chronic exposure of the opioid receptor (tolerance) may be the consequence of the
      down-regulation or desensitization phenomenon (where the total number of
      receptors coupled to the second messenger is reduced). The agonist dose-response
      begins to shift to the right. The dramatic analgesic improvement obtained with
      subanaesthetic doses of ketamine, an NMDA receptor antagonist, in those of our
      cancer patients who have become resistant to morphine is intriguing. As shown for
      tolerance, insensitivity to opioids may represent a rightward shift in the opioid
      dose-response curve and the analgesic effect of ketamine the reversal of that
      shift.

PMID- 8143107
TI  - Hickman catheters in association with intensive cancer chemotherapy.
AB  - Hickman catheters were the major venous access devices utilized at the University
      of Maryland Cancer Center from November 1978 to 1987. This study provided an
      opportunity to standardize insertion technique, to manage catheter-related
      activities and daily maintenance procedures in order to examine the progression
      of Hickman-catheter-related problems, to identify those factors that may minimize
      them, and to develop guidelines for the management and prevention of
      complications and malfunctions. In all, 690 Hickman catheters (368 double lumens)
      were placed in patients with acute leukemia and other cancers: 401 catheters were
      placed in patients with leukemia; 269 were placed during neutropenia; and 230 at
      platelet counts of < 50,000/microliters. Two surgeons inserted 490 catheters, and
      the remaining 200 were placed by a group of rotating surgeons. All catheters were
      placed with the intention that they would remain in place as long as clinically
      necessary. Total Hickman catheter days were 134273. Infectious complications
      included exit site infections (160), tunnel infections (46) and bacteremias
      (397). There were 438 instances of noninfectious complications including
      thrombosis, lack of function, catheter migration, fracture and hemorrhage.
      Recommendations for prevention and treatment of Hickman-catheter-related
      complications include the development of a select group committed to placement,
      daily maintenance and management of problems; prompt removal of catheters with
      Candida sp. fungemia and bacteremia due to Bacillus sp. or a bacteremia that
      persists for > 48 h after initiation of appropriate antibiotics, tunnel
      infections or Hickman-catheter-associated thrombosis. The majority of bacteremias
      and exit site infections can be effectively treated with antibiotics and local
      care.

PMID- 8143108
TI  - A circadian distribution to febrile episodes in neutropenic patients.
AB  - Four-hourly temperature charts relating to 63 febrile neutropenic episodes in 32
      patients were assessed for a circadian distribution to the onset of fever (> 37.5
      degrees C) using the Edward's test. A highly significant distribution was found
      with the maximum incidence of febrile events between the hours of 5 p.m. and
      midnight (acrophase 9.30 p.m.). Patients were 5.53 times more likely to develop
      fever at 9.30 p.m. that 9.30 a.m.

PMID- 8143109
TI  - Trends in infection, virulence and pathogenesis.

PMID- 8143110
TI  - The fungal genus Cochliobolus and toxin-mediated plant disease.
AB  - Several times in this century, new and sometimes devastating diseases of cereal
      crops, caused by fungi in the genus Cochliobolus, have suddenly appeared. In many
      fungal diseases of plants the factors required for pathogenicity are unknown; in
      contrast, the key elements in each of several Cochliobolus diseases are known to
      be host-selective toxins. Recent research on these systems has given surprising
      insights into the genetic basis of fungal pathogenicity and plant susceptibility
      to disease.

PMID- 8143111
TI  - Viral acylproteins: greasing the wheels of assembly.
AB  - Viruses take advantage of the host's protein modification and targeting pathways
      to modify their own proteins and to ensure that they assume active configurations
      and locate appropriately for assembly. In many viruses, one recurrent theme in
      such processes is exploitation of cellular protein acylation pathways for the
      addition of myristic and palmitic acid to capsid or envelope proteins.

PMID- 8143112
TI  - The wily ways of a parasite: induction of actin assembly by Listeria.
AB  - The intracellular pathogen Listeria has a spectacular mode of transport within
      and between host cells. By inducing host cell actin to assemble from its surface,
      the bacterium forms a tail composed of many short, crossbridged actin filaments.
      With this tail Listeria is propelled across the cytoplasm like a comet streaking
      across the sky. Here we discuss the antics of Listeria and some of the bacterial
      genes instrumental in maintaining it in the host.

PMID- 8143113
TI  - Subversion of host immune responses by viral superantigens.
AB  - Recent experiments with mouse mammary tumor virus indicate that expression of a
      virally encoded superantigen by B cells and its subsequent recognition by T cells
      are essential steps for amplification of infection and virus transmission.
      Preliminary results suggest that superantigens may also be expressed during
      retroviral infection in humans.

PMID- 8143114
TI  - Do nonclassical, class Ib MHC molecules present bacterial antigens to T cells?
AB  - Immune responses to bacterial antigens that appear unrestricted by the MHC may
      involve oligomorphic MHC class Ib molecules. One example is H-2M3, which binds N
      formylated peptides and presents a Listeria peptide to cytotoxic T cells from
      infected mice. Lack of polymorphism makes these molecules a promising target for
      peptide vaccines.

PMID- 8143115
TI  - Uptake of iron-siderophore complexes across the bacterial outer membrane.

PMID- 8143116
TI  - The balance of power between HIV and the immune system.
AB  - There are several theories of the pathogenesis of HIV that attempt to explain the
      long and variable delay between infection and disease. Here, each theory is
      reviewed within the context of a simple mathematical model of the interactions
      between HIV and the immune system. From this model, a theoretical index of
      progression has been derived that combines elements from each proposed mechanism.

PMID- 8143117
TI  - Cell-to-cell movement of plant viruses.
AB  - To establish an infection, most plant viruses move from cell to cell in the
      plant. Virus-encoded movement proteins mediate this process and appear to use two
      mechanisms for transport. Both mechanisms involve interaction with and potential
      modification of plant intercellular connections, the plasmodesmata. Thus,
      although viral movement proteins are a diverse group, they share an ability to
      interact with specific plant components.

PMID- 8143118
TI  - Molecular mechanisms of isoniazid: a drug at the front line of tuberculosis
      control.
AB  - The resurgence of tuberculosis and emergence of multidrug-resistant isolates has
      focused attention on the need for an improved understanding of molecular aspects
      of the disease, and for elucidation of the factors responsible for drug action
      and resistance. Recent research has probed the mechanism of action of isoniazid
      (INH), a key drug in the chemotherapy of tuberculosis.

PMID- 8143119
TI  - Programmed cell death in infectious diseases.
AB  - Apoptosis plays an important role during normal animal development, and in
      proliferative and degenerative diseases. It is perhaps not surprising that
      apoptosis can be manipulated by infectious microorganisms to their own advantage,
      either to promote host cell immortality or to combat cells of the immune system.

PMID- 8143120
TI  - The role of CD8+ T cells in immunity to tuberculosis infection.

PMID- 8143121
TI  - Protease-dependent virus tropism and pathogenicity.
AB  - Viral tissue tropism in a susceptible host is often determined by virus-receptor
      interactions. Nevertheless, closely related viruses utilizing the same receptor
      molecules can display striking differences in tropism, or a virus can cause a
      localized infection despite the widespread occurrence of the receptor. These
      events are now explained by another mechanism of tropism, in which host proteases
      play a major role by activating viral fusion glycoproteins.

PMID- 8143122
TI  - Salicylic acid: a systemic signal in induced plant disease resistance.
AB  - Some plants respond to infection by pathogens with both localized and systemic
      resistance responses. These prevent the spread of the disease-causing organism
      and reduce the severity of a subsequent infection. Recent evidence suggests that
      systemic increases in the host's salicylic acid levels act as a signal for the
      activation of at least some of these induced defenses.

PMID- 8143123
TI  - DNA topology and bacterial virulence gene regulation.
AB  - The topology of bacterial DNA varies in response to extracellular environmental
      stimuli, providing a possible mechanism for environmental control of gene
      expression during bacterial pathogenesis. The contribution of DNA topology to the
      control of transcription is complex, but an appreciation of the distinction
      between local and global DNA topological effects is helping to clarify this
      complexity.

PMID- 8143124
TI  - Macrophage control of Brucella abortus: influence of cytokines and iron.
AB  - Brucella abortus is a facultative intracellular bacterium that can infect and
      replicate in mononuclear phagocytes. Recent work has elucidated the role of
      cytokines in activating macrophages to inhibit the intracellular replication of
      brucellae, and in recruiting macrophages to the site of infection in vivo. There
      is also evidence that iron increases the ability of cytokine-activated
      macrophages to control intracellular brucellae by mechanisms involving reactive
      oxygen intermediates.

PMID- 8143125
TI  - The class II MHC and HIV-1 binding surfaces of CD4.

PMID- 8143126
TI  - Ordered duplex RNA in an icosahedral virus.

PMID- 8143127
TI  - Targeting of viral glycoproteins to the Golgi complex.
AB  - Certain enveloped viruses are known to assemble on membranes of the Golgi
      complex. Intracellular budding is facilitated by targeting of the viral
      glycoproteins to this organelle. It is likely that these viral glycoproteins are
      retained in the Golgi by the same means as are endogenous Golgi proteins.
      Consequently, the study of Golgi-specific viral proteins has provided important
      clues to the nature of Golgi retention signals.

PMID- 8143128
TI  - HTLV-1 Tax: regulation of gene expression and disease.
AB  - The human T cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes adult
      T cell leukemia and the neurological disorder tropical spastic paraparesis.
      Pathology apparently results from the activities of the Tax protein, which trans
      activates the expression of viral and cellular genes by binding to various
      enhancer-binding proteins needed for transcription. This ultimately results in
      cell transformation, immortalization and disease.

PMID- 8143129
TI  - Nonhost resistance genes and race-specific resistance.
AB  - Apart from physical barriers, plants have two major types of defense against
      potential pathogens. In 'race-specific' resistance, plants match single mendelian
      resistance genes with the 'avirulence' genes possessed by races of a pathogen.
      Plants also employ the more complex and evolutionarily more robust system of
      'nonhost resistance' against a broad range of pathogenic species. In peas, both
      types of resistance are associated with the expression of a common group of
      'resistance response' genes.

PMID- 8143130
TI  - Acquisition and storage of inorganic iron and hemin by the yersiniae.
AB  - Pathogenic Yersinia express a complex array of iron-regulated functions and
      possess mechanisms for inorganic iron and hemin acquisition. These include a
      unique temperature-regulated hemin storage system, high-affinity transport
      processes for hemin and inorganic iron, and an iron-responsive regulatory system
      controlling gene expression. The genetic organization of these systems
      illuminates several aspects of iron metabolism in the yersiniae.

PMID- 8143131
TI  - Human endogenous retroviral elements and autoimmunity: data and concepts.
AB  - The human genome contains a complex variety of inherited endogenous retroviral
      sequences (ERSs), several of which are transcriptionally active and contain open
      reading frames. Aberrant expression of ERSs and generation of antibodies to ERS
      encoded proteins have recently been revealed in autoimmune disorders. Involvement
      of ERSs could explain both the familial aggregation and the detection of
      antiretroviral antibodies in autoimmune diseases.

PMID- 8143132
TI  - Frameshifting and antigenic variation in respiratory syncytial virus.
AB  - Recent studies have suggested that frameshift mutations in the attachment protein
      gene of respiratory syncytial (RS) virus may contribute to its variability. Many
      pathogens use several mechanisms for antigenic variation to elude their hosts'
      immune responses, and the frameshift mechanism is not unique to RS virus. Indeed,
      it may turn out to be a widespread genetic phenomenon among pathogens.

PMID- 8143133
TI  - Proteins with transcription regulatory properties encoded by human adenoviruses.
AB  - Of the more than 30 genes encoded by the adenovirus genome, no less than six have
      been shown to encode proteins that have transcription regulatory properties. None
      of them is a sequence-specific DNA-binding protein. They act to modulate the
      activity of cellular transcription factors by causing their phosphorylation or
      dephosphorylation, by physically interacting with them, or by dissociating
      transcription factor inhibitory protein complexes.

PMID- 8143134
TI  - Novel targets and catalytic activities of bacterial protein toxins.
AB  - Among bacterial protein toxins with intracellular targets, tetanus and botulinum
      toxins form a group with unique properties. They are absolutely neurospecific and
      act in the cytosol of neurons. Recent evidence indicates that they are zinc
      proteases specific for proteins of the neuroexocytosis apparatus.

PMID- 8143135
TI  - Conservation of secretion pathways for pathogenicity determinants of plant and
      animal bacteria.
AB  - Extracellular proteins of plant and animal bacteria are important in virulence.
      Many of these are secreted through the type I sec-independent and the type II sec
      dependent pathways. Recently, a third distinct pathway, involved in secretion of
      Yops, has been discovered in Yersinia. This pathway has homology with pathways in
      plant pathogenic bacteria that are putatively involved in the secretion of
      proteins active on plant cells, such as harpin and possibly some avr gene
      products

PMID- 8143136
TI  - Microbial recognition and activation of plant defense systems.
AB  - Molecules released or generated during microbial entry (elicitors) are recognized
      by components of plant cells, ultimately resulting in the induction of a battery
      of plant defense responses. The molecular mechanisms underlying these signaling
      systems, as well as the plant defense responses they control, are becoming
      increasingly well characterized.

PMID- 8143137
TI  - Calmodulin-activated bacterial adenylate cyclases as virulence factors.
AB  - Bordetella pertussis and Bacillus anthracis each produce a virulence-associated,
      calmodulin-dependent adenylate cyclase toxin, which generates increased levels of
      cyclic AMP in eukaryotic cells. The two proteins share sequence similarities in
      their catalytic domains. The remaining regions display different structural and
      functional organizations that account for the differences both in interaction of
      the two toxins with target cells and in the resulting disease symptoms.

PMID- 8143138
TI  - Attachment factors of Bordetella pertussis: mimicry of eukaryotic cell
      recognition molecules.
AB  - Bacteria localize to specific target organs during infection by recognizing
      eukaryotic cell surface addresses. This address system exists to facilitate
      normal trafficking of host cells such as leukocytes. The mechanisms by which
      bacteria subvert host targeting codes provide a unique link between microbial
      pathogenesis and eukaryotic cell trafficking, and can point to a new array of
      antibodies and peptides of potential therapeutic value.

PMID- 8143139
TI  - Fungal symbionts of grasses: evolutionary insights and agricultural potential.
AB  - Some filamentous fungal endophytes confer on their grass hosts important
      biological properties including resistance to grazing herbivores and resistance
      to nematodes and some fungal pathogens, as well as drought tolerance and greater
      field persistence. The production of alkaloids toxic to grazing animals is an
      undesirable aspect of the association in agronomic situations. Consequently,
      genetic strategies are being pursued to manipulate fungal endophytes and their
      hosts for agricultural benefit.

PMID- 8143140
TI  - Structural organization of TonB-dependent receptors.

PMID- 8143141
TI  - Beyond ACP Journal Club: how to harness MEDLINE to solve clinical problems.

PMID- 8143142
TI  - Scheduled replacement of central vascular catheters.

PMID- 8143143
TI  - Anatomical identification of a telencephalic somatosensory area in a reptile,
      Caiman crocodilus.
AB  - Telencephalic projections of a thalamic somatosensory area were investigated in a
      reptilian species, Caiman crocodilus, by means of horseradish peroxidase (HRP)
      neurohistochemistry. Injections of HRP into the medialis complex labeled axons
      that leave the ventral aspect of this nucleus to enter the dorsal peduncle of the
      lateral forebrain bundle where they ascend. These fibers course rostrally to
      enter the central portion of the lateral forebrain bundle. Here, axons turn
      dorsally, pass through, and probably synapse on, interposed neurons of the
      ventrolateral area, to end in a central portion of the dorsal ventricular ridge
      (DVR). These findings were confirmed by HRP injections into this somatosensory
      area of the DVR that retrogradely labeled neurons in the medialis complex. This
      telencephalic somatosensory area identified in transverse sections was then
      reconstructed onto a surface view of the DVR. The locus of this forebrain
      somesthetic region was then compared with the location of the DVR projection
      areas of auditory (nucleus reuniens) and visual (nucleus rotundus) thalamic
      nuclei. This analysis suggested two features. First, telencephalic terminal zones
      of dorsal thalamic nuclei were largely separate and non-overlapping. Second, the
      locus of termination in the DVR of each thalamic nucleus reflected each nucleus's
      topography in the dorsal thalamus. Additional parallels in the neural circuitry
      of auditory, visual, and somatosensory systems that synapse in the midbrain and
      project to the DVR are documented.

PMID- 8143144
TI  - GnRH cell size and number in a teleost fish with two male reproductive morphs:
      sexual maturation, final sexual status and body size allometry.
AB  - Gonadotropin releasing hormone-like immunoreactive (GnRH-ir) cells in both the
      ganglion of the terminal nerve (TN) and the preoptic area (POA) have been
      implicated in the development and maintenance of reproductive behavior and
      physiology in teleost fishes. One marine species, the plainfin midshipman,
      Porichthys notatus, exhibits two sexually mature male morphs (types I and II)
      which differ with respect to size at sexual maturation, gonad/body weight index,
      reproductive tactic and vocal motor traits. Type II males become reproductively
      active at a smaller body size than either females or type I males.
      Immunocytochemical techniques and quantitative analyses were used here to
      determine the size and number of GnRH-ir cells in the TN and POA amongst field
      collected juveniles, sexually mature females, and type I and II males. Mean GnRH
      ir cell size and number in the TN did not vary across the entire range of
      specimens. However, mean GnRH-ir cell size and number in the POA were 50-100%
      greater in sexually mature adults compared to juveniles. Analyses of covariance
      indicated that increases in cell number, but not cell size, could be explained
      solely on the basis of changes in body size. However, regression analyses showed
      that body size had a significant influence on increasing cell number only in the
      juvenile-type I male transition and the juvenile-female transition, not in the
      juvenile-type II male transition. The latter suggests that type II males, unlike
      the other adult morphs, have 'escaped' from a body size constraint imposed on
      increasing GnRH-ir cell number in the POA. There were also significant
      differences among the adult morphs in the size of GnRH-ir POA cells that could
      not be explained on the basis of differences in body size but, rather, appear to
      reflect differences in the temporal onset of sexual maturation. Together, the
      data suggest that the timing of changes in POA phenotype may provide a proximate
      mechanism permitting the development of alternative male reproductive morphs.

PMID- 8143145
TI  - Cell types in the mustached bat auditory cortex.
AB  - Cells in the auditory cortex of the mustached bat were studied with Golgi stains.
      No cell types appeared to be unique to the mustached bat auditory cortex or to
      specialized functional areas, but the laminar proportions and distributions of
      cell types were somewhat different from that reported for primary sensory cortex
      of other species. Two major cell types were distinguished, those with dendritic
      spines and those without spines. Non-spiny neurons were concentrated deep in
      layer III/IV and in layer V, and had three types of dendritic patterns,
      multipolar, bitufted and bipolar. Many of the non-spiny neurons were large; some
      nearly equaled the largest pyramidal neurons in size. Five types of spiny neurons
      were identified, pyramidal cells, extraverted pyramidal cells, 'spiny stellate
      like' neurons, and multiform cells. In the narrow, densely packed, 'accentuated'
      layer II, slightly more than half of the spiny neurons were extraverted pyramidal
      cells, which are characterized by multiple, widely diverging apical dendrites.
      The high concentration of layer II extraverted pyramidal neurons is consistent
      with descriptions of the 'accentuated' layer II previously reported in other bat
      species and 'basal' insectivores. The remaining spiny neurons in layer II, and
      the preponderance of spiny neurons in layers III-VI, were typical pyramidal
      neurons that had single apical dendrites and tufts of basal dendrites. The
      thalamic recipient zone (deep layer III/IV) contained few candidates for spiny
      stellate cells, so a major constituent of the thalamic recipient zone in primary
      sensory cortex of many species is only a minor cellular component in the
      mustached bat auditory cortex.

PMID- 8143146
TI  - Julia B. Platt (1857-1935): pioneer comparative embryologist and neuroscientist.
AB  - Julia Barlow Platt was a comparative embryologist and neurobiologist who was
      primarily interested in segmentation of the head in vertebrates. She was born on
      September 14, 1857 in San Francisco, California. Platt grew up in Burlington,
      Vermont, attended the University of Vermont and began graduate studies at Harvard
      University. Her nine years as a graduate student were spent on two continents
      with some of the most influential comparative zoologists of the time. Platt's
      remarkable scientific accomplishments over a ten year period include a
      description of axial segmentation currently used in the staging of chick embryos
      and the first description of a separate anterior head segment in Squalus embryos.
      Her most controversial study identified ectodermal cells in Necturus embryos that
      gave rise to head cartilage and dentine, a discovery which was the impetus for
      the reassessment and modification of the germ layer concept. She was one of the
      first women to 'matriculate' at a German university and receive a Ph.D. degree.
      Platt played a pioneer role in opening opportunities for other women who followed
      her. Platt was one of the first women neuroscientists. Among her contributions,
      she distinguished dorsolateral placodes, epibranchial placodes, and the first
      stages of lateral line organs in Necturus, and she described nerve fibers
      originating in the spinal cord and extending to the notochord in Branchiostoma (=
      Amphioxus). After receiving a Ph.D. degree in Freiburg, Germany in 1898, Platt
      was unable to secure a suitable teaching position and, as a result, her
      scientific career came to an end. She retired to Pacific Grove, California, where
      she pursued civic duty with the same vigor and energy she had dedicated to
      scientific research. We provide a sketch of her remarkable life and work as a
      comparative embryologist, neuroscientist and civic leader.

PMID- 8143147
TI  - STADEERS: a software package for the statistical design of experiments pertaining
      to the estimation of parameters in rate expressions that describe enzyme
      catalyzed processes.
AB  - This paper describes a computational algorithm (STADEERS--STAtistical Design of
      Experiments in Enzyme ReactorS) for the statistical design of biochemical
      engineering experiments. The type of experiment that qualifies for this package
      involves a batch reaction catalyzed by a soluble enzyme where the activity of the
      enzyme decays with time. Assuming that both the catalytic action and the
      deactivation of the enzyme obey known rate expressions, the present code is
      helpful in the process of obtaining estimates of the kinetic parameters by
      providing as output the times at which samples should be withdrawn from the
      reacting mixture. Starting D-optimal design is used as a basis for the
      statistical approach. This BASIC code is a powerful tool when fitting a rate
      expression to data because it increases the effectiveness of experimentation by
      helping the biochemical kineticist obtain data points with the largest possible
      informational content.

PMID- 8143148
TI  - ENVIRON: a software package to compare protein three-dimensional structures with
      homologous sequences using local structural motifs.
AB  - This work presents a method to compare local clusters of interacting residues as
      observed in a known three-dimensional protein structure with corresponding
      clusters inferred from homologous protein sequences, assuming conserved protein
      folding. For this purpose the local environment of a selected residue in a known
      protein structure is defined as the ensemble of amino acids in contact with it in
      the folded state. Using a multiple sequence alignment to identify corresponding
      residues in homologous proteins, a detailed comparison can be performed between
      the local environment of a selected amino acid in the template protein structure
      and the expected local environments at the sets of equivalent residues, derived
      from the aligned protein sequences. The comparison makes it possible to detect
      conserved local features such as hydrogen bonding or complementarity in residue
      substitution. A global measure of environmental similarity is also defined, to
      search for conserved amino acid clusters subject to functional or structural
      constraints. The proposed approach is useful for investigating protein function
      as well as for site-directed mutagenesis experiments, where appropriate amino
      acid substitutions can be suggested by observing naturally occurring protein
      variants.

PMID- 8143149
TI  - Enrichment of oligonucleotide sets with transcription control signals. III: DNA
      from non-mammalian vertebrates.
AB  - We studied the frequency distribution of 1,048,576 oligonucleotides 10 bp long in
      a sample of 1.072 x 10(6) bases of genes from non-mammalian vertebrates, made of
      322 sequences extracted from EMBL(R) 29.0, with the aim of detecting
      transcription control signals. Among all decamers, 2097 (0.2%) had a frequency 10
      times higher than the mean and were subjected to further statistical analysis.
      For each of the 2097 decamers (parents), we counted the individual frequencies of
      the 30 decamers differing from the parent by one base mutation (progeny) and we
      calculated two variance/mean chi squares for the progeny, with and without the
      parent decamer. By studying the distribution of the ratio between the two chi
      squares we observed that out of 2097 decamers that occurred > 10 times more
      frequently than average, 1017 had a chi square ratio of between 1 and 1.5; in
      this final set, which corresponds to < 0.097% of all possible decamers, 75
      decamers were found to contain 100 transcription control elements, like CCAAT and
      others. The final set contains a high excess of signals when compared to 100
      random sets of 1017 decamers. Some of the decamers selected with the procedure
      are members of consensus sequences rather than unique sequences.

PMID- 8143150
TI  - A consensus program for molecular sequences.
AB  - Although molecular biologists often calculate consensus sequences from aligned
      DNA or protein sequences, relatively little is known about the properties of many
      of the consensus methods being used. Consequently, we wrote a program, CONSENSUS,
      to analyze and compare methods of calculating a consensus result (a base, an
      ambiguity code or a subset of codes) at a position in an aligned set of molecular
      sequences. The program supports alphabets of up to four symbols (e.g. [R,Y] or
      [A,C,G,T]). The program's output makes it suitable for exploratory data analysis
      or for selecting values of thresholds or confidence levels in consensus methods
      having such parameters.

PMID- 8143151
TI  - Expertise in expert systems: knowledge acquisition for biological expert systems.
AB  - In this paper it is argued that an expert system requires more than factual
      knowledge before it can display expertise in a given domain. The additional
      knowledge consists of the heuristics or 'rules of thumb' used by an expert to
      manipulate and interpret the factual knowledge. The knowledge acquisition phase
      of an expert system project involves determining the factual knowledge (which may
      be obtained from published sources) and the heuristics used by an expert to
      manipulate that knowledge--these heuristics can only be obtained from an expert.
      In reviewing existing biological expert systems it is apparent that many contain
      only the factual knowledge relating to the domain, and lack the heuristics that
      enable such systems to show expertise. This paper reviews a number of knowledge
      acquisition techniques which could be used for acquiring heuristic knowledge and
      discusses when their use is appropriate. The knowledge acquisition techniques
      discussed are those suitable for the development of small-scale expert systems as
      these are most likely to be of interest to biologists. The techniques include the
      use of questionnaires, interview techniques and protocol analysis; particular
      emphasis is placed on a modification to the 'twenty questions' interview
      technique which was developed specifically to elicit taxonomic knowledge relating
      to water mite identification.

PMID- 8143152
TI  - OMEGA: a three-dimensional databank for protein structures (a complement to PDB).
AB  - OMEGA is a compilation of recent structural information on proteins derived from
      X-ray crystallography or NMR and published in journals referenced by Current
      Contents. To date, 401 entries have been included (334 X-ray, 28 NMR, 5 NMR + X
      ray, 5 electron microscopy, 3 neutron scattering, 2 neutron diffraction, 1
      electron microscopy + X-ray, 12 model, 11 miscellaneous), with 5-10 new proteins
      being added each week. OMEGA can be accessed on Macintosh and is interrogated
      through 32 key words (space group, resolution, secondary structure, number of
      residues, etc). This pool of proteins could be used for various purposes,
      including searches for proteins with a particular set of secondary structures.
      OMEGA will be continuously updated (every 6 months) and may later include all
      proteins already reported in the PDB, as well as structures reported in journals
      with smaller readerships.

PMID- 8143153
TI  - A hybrid method to cluster protein sequences based on statistics and artificial
      neural networks.
AB  - We have recently proposed a method, based on artificial neural networks (ANNs) to
      cluster protein sequences into families according to their degree of sequence
      similarity. The network was trained with an unsupervised learning algorithm,
      using, as inputs, matrix patterns derived from the bipeptide composition of the
      protein sequences. We describe here some further improvements to that approach.
      First, we propose a statistical method to cluster a set of bipeptidic matrices
      into families. It consists of three stages: (i) principal component analysis,
      (ii) determination of the optimal number M of clusters and (iii) final
      classification of the bipeptidic matrices into M clusters. Using a set of 444
      protein sequences, we show that the classification given by the statistical
      method is in agreement with biological knowledge. We also show that the resulting
      classification is very similar to the one previously obtained with the ANN
      approach. Finally, we propose a new hybrid method of the statistical and ANN
      approaches, in which the results of the statistical method are used to choose the
      number of neurons and inputs of the network. We show that a network built in this
      way, and fed with a few principal components of the set of bipeptidic matrices as
      input signals, can be trained in an extremely short computing time. The resulting
      topological maps do not essentially differ from the ones obtained with the
      initial ANN approach.

PMID- 8143154
TI  - FT3D: three-dimensional Fourier analysis on small Unix workstations for electron
      microscopy and tomographic studies.
AB  - FT3D is a self-contained package of tools for three-dimensional Fourier analysis,
      written in the C language for Unix workstations. It can evaluate direct
      transforms of three-dimensional real functions, inverse transforms, auto- and
      cross-correlations and spectra. The library has been developed to support three
      dimensional reconstructions of biological structures from projections obtained in
      the electron microscope. This paper discusses some features of the library, which
      has been implemented in such a way as to profit from the resources of modern
      workstations. A table of elapsed times for jobs of different dimensions with
      different RAM buffers is reported for the particular hardware used in the
      authors' laboratory.

PMID- 8143155
TI  - Potentially functional regions of nucleic acids recognized by a Kohonen's self
      organizing map.
AB  - Computer recognition of short functional sites on DNA, such as promoter regions
      or intron-exon boundaries, has recently attracted much interest. In this paper we
      have focused our attention on the automatic recognition of relevant features of
      human nucleic acid sequences by means of an unsupervised artificial neural
      network model. Sixty messenger RNA and 31 genomic DNA sequences were analysed.
      The results showed that in mRNA, the minimal similarity 60 base pattern was
      guanine- and cytosine-rich and located in most sequences in a range of 250 bases
      from either the middle point of the signal peptide coding region or from the
      start of the coding region. On DNA sequences a region defined by a cluster of
      minimal similarity patterns was present in many of the analysed genes. This zone
      may be related to alternative splicing and DNA methylation.

PMID- 8143156
TI  - APLOGEN: an object-oriented genetic algorithm performing Monte Carlo
      optimization.
AB  - Problem-solving and modelling within a biological context often need a level of
      descriptive accuracy that is unlikely to be capable of analytical treatment,
      especially if the mathematical background of the biologist is poor. Furthermore
      solver-model maintenance is often difficult without the availability of trained
      specialists. Better prospects are found in the genetic algorithm field. Genetic
      algorithms are a set of procedures formulated to solve complex problems without
      specifying rules for intermediate steps. This approach becomes feasible
      performing a Monte Carlo simulation of the natural evolution process, in which
      population improvement (search for solutions) in a considered environment (the
      specific problem domain) is achieved by following the genetic paradigm. Starting
      with a randomly constituted sample of individuals, drawn from the population of
      admissible values and expressed as binary strings, random mating brings about
      individuals of the next generation. Parents are chosen with a greater probability
      as the number of constraints violated by each individual becomes smaller. During
      the constitution of each generation the presence of some genetic operators causes
      the improvement of population diversity and its maintenance. Genetic operators
      are simple string transformation rules, generally independent of a specific
      context. We have developed the constant core of a minimal genetic algorithm, from
      which can be derived genetic problem-solvers in specific domains. An applicative
      example--a constrained matrix equation on signed integers--is also realized to
      show graphically the algorithm dynamics.

PMID- 8143157
TI  - SIMD parallelization of the WORDUP algorithm for detecting statistically
      significant patterns in DNA sequences.
AB  - The development of new techniques in sequencing nuclei acids has produced a great
      amount of sequence data and has led to the discovery of new relationships. In
      this paper, we study a method for parallelizing the algorithm WORDUP, which
      detects the presence of statistically significant patterns in DNA sequences.
      WORDUP implements an efficient method to identify the presence of statistically
      significant oligomers in a non-homologous group of sequences. It is based on a
      modified version of the Boyer-Moore algorithm, which is one of the fastest
      algorithms for string matching available in the literature. The aim of the
      parallel version of WORDUP presented here is to speed up the computational time
      and allow the analysis of a greater set of longer nucleotide sequences, which is
      usually impractical with sequential algorithms.

PMID- 8143158
TI  - Protein motif by computer: the perfect Greek key jellyroll designer.
AB  - A program that generates amino acid sequences that are compatible with the Greek
      key protein motif is presented. Using statistical data derived from the
      structures of molecules from the protein databank, the novel algorithm generates
      amino acid sequences compatible with an 8-stranded perfect Greek key jellyroll
      motif. In this motif, all hydrogen bonds present in the theoretical originating
      beta-hairpin stay in register as the whole 8-stranded domain folds at once in an
      anticlockwise swirl. Eight residues are generated per strand and 32 residues per
      sheet making 64 residues in the antiparallel beta-barrel. The seven loops between
      beta-strands contain an additional 27 residues. All recognized features of beta
      sheets and beta-strands, such as alternating hydrophobic, hydrophilic residues
      with hydrophobics on the narrow-hydrogen-bond-pair, concave side of the
      theoretical originating beta-ribbon; sheet twist, strand twist, side chain
      rotation about the strands; the theories of side chain packing between the
      sheets; an average 30 degrees rotation between beta-sheets; the theoretical
      anticomplementary patch residues of each sheet; and the anticomplementary,
      isotropically stressed hyperbolic parabloid shape of each sheet, are taken into
      account in the program. The sequences of the loops between strands are designed
      by turn type and strand twist is considered in the design of the motif's single
      beta-hairpin turn. Secondary structure parameters and between-strand amino acid
      pair correlations also figure importantly in the novel algorithm.

PMID- 8143159
TI  - Primary sequence analysis and representation techniques in carbohydrates.
AB  - Sequence similarity calculations of carbohydrates present several problems which
      must be addressed if a computer implementation is to be achieved. These problems
      range from the computational representation of the complex carbohydrate structure
      to the method by which the comparison of residue and linkage is to be made. This
      paper therefore discusses the form of this representation and how two or more
      carbohydrates can be meaningful compared. An example set of results using this
      approach is presented and discussed to illustrate how similarity comparison can
      show relationships between carbohydrates, features that are otherwise hidden by
      the sheer volume of data which must be considered.

PMID- 8143160
TI  - An efficient algorithm to locate all locally optimal alignments between two
      sequences allowing for gaps.
AB  - An efficient algorithm is described to locate locally optimal alignments between
      two sequences allowing for insertions and deletions. The algorithm is based on
      that of Smith and Waterman which returns the single best local alignment.
      However, the algorithm described here permits all non-intersecting locally
      optimal alignments to be determined in a single pass through the comparison
      matrix. The algorithm simplifies the location of repeats, multiple domains and
      shuffled motifs, and is fast enough to be used on a conventional workstation to
      scan large sequence databanks.

PMID- 8143161
TI  - CEDIT: a C interface and macro facility for protein sequence alignment editing in
      colour with Microsoft Word 5.0 for PCs.
AB  - CEDIT, a C interface and macro facility that provides for the colour editing of
      protein sequence alignments (up to 2000 sequences, 5000 residues each) using
      Microsoft Word 5.0 for PCs is presented. CEDIT uses the ability of MS-Word 5.0 to
      display letters with the desired colour to easily identify conservative
      homologies across the sequences. A glossary file with useful macros for the
      sequence editing is provided, along with several utilities programs for error
      checking, estimating sequence similarities and homology significance. CEDIT has a
      menu interface and a context sensitive help.

PMID- 8143162
TI  - Protein sequence alignments: a strategy for the hierarchical analysis of residue
      conservation.
AB  - An algorithm is described for the systematic characterization of the physico
      chemical properties seen at each position in a multiple protein sequence
      alignment. The new algorithm allows questions important in the design of
      mutagenesis experiments to be quickly answered since positions in the alignment
      that show unusual or interesting residue substitution patterns may be rapidly
      identified. The strategy is based on a flexible set-based description of amino
      acid properties, which is used to define the conservation between any group of
      amino acids. Sequences in the alignment are gathered into subgroups on the basis
      of sequence similarity, functional, evolutionary or other criteria. All pairs of
      subgroups are then compared to highlight positions that confer the unique
      features of each subgroup. The algorithm is encoded in the computer program AMAS
      (Analysis of Multiply Aligned Sequences) which provides a textual summary of the
      analysis and an annotated (boxed, shaded and/or coloured) multiple sequence
      alignment. The algorithm is illustrated by application to an alignment of 67 SH2
      domains where patterns of conserved hydrophobic residues that constitute the
      protein core are highlighted. The analysis of charge conservation across annexin
      domains identifies the locations at which conserved charges change sign. The
      algorithm simplifies the analysis of multiple sequence data by condensing the
      mass of information present, and thus allows the rapid identification of
      substitutions of structural and functional importance.

PMID- 8143163
TI  - A user-friendly Hypercard interface for human linkage analysis.
AB  - The availability of a large number of highly informative genetic markers has made
      human linkage analysis faster and easier to perform. However, current linkage
      analysis software does not provide an organizational database into which a large
      body of linkage data can be easily stored and manipulated. This manual entry and
      editing of linkage data is often time consuming and prone to typing errors. In
      addition, the large number of alleles in many of these markers must be reduced in
      order to perform linkage analysis with multiple loci across large genetic
      distances. This reduction in allele number is often difficult and confusing,
      especially in large pedigrees. We have taken advantage of the Macintosh-based
      Hypercard program to develop an interface with which linkage data can be easily
      stored, retrieved and edited. For each family, the components of the pedigree,
      including ID numbers, sex and affection status, only need to be entered once. The
      program (Linkage Interface) retrieves this information each time the data from a
      new polymorphic marker is entered. Linkage Interface has flexible editing
      capabilities that allow the user to change any portion of the pedigree, including
      the addition or deletion of family members, without affecting previously entered
      genotype data. Linkage Interface can also analyze both the pedigree and marker
      data and will detect any inconsistencies in inheritance patterns. In addition,
      the program can reduce the number of alleles for a polymorphic marker. Linkage
      Interface will then compare the 'reduced' data to the original marker data and
      assists in maintaining all informative meioses by pointing out which meioses have
      become non-informative.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143164
TI  - MacP12: a protein property multi-profile plot program for the Apple Macintosh.
AB  - MacP12, a program for the Apple Macintosh, allows simultaneous plotting of two
      protein property profiles selectable from 12 built-in amino acid property scales.
      Various parameters such as the region to be analyzed, the size of the sliding
      window, the weighting function and the size of the graphical output can be easily
      adjusted by the user, which makes this program appropriate for diverse research
      questions. Since built-in scales can be simply exchanged, MacP12 is adaptable to
      the specific needs of the individual user.

PMID- 8143165
TI  - [Advances in cardiovascular diseases in China].

PMID- 8143166
TI  - [Advances in hematologic diseases].

PMID- 8143167
TI  - [Advances in digestive system diseases].

PMID- 8143168
TI  - [Advances in endocrine diseases].

PMID- 8143169
TI  - [Advances in nephrology].

PMID- 8143170
TI  - [Advances in diabetes mellitus].

PMID- 8143171
TI  - [Advances in rheumatology].

PMID- 8143172
TI  - [Advances in abdominal surgery].

PMID- 8143173
TI  - [Advances in cardiovascular surgery].

PMID- 8143174
TI  - [Advances in orthopedics].

PMID- 8143175
TI  - [Advances in organ transplantation].

PMID- 8143176
TI  - [Advances in neurosurgery].

PMID- 8143177
TI  - [Advances in burns and plastic surgery].

PMID- 8143178
TI  - [Advances in gynecology].

PMID- 8143179
TI  - [Advances in perinatology].

PMID- 8143180
TI  - [Advances in family planning].

PMID- 8143181
TI  - [Advances in pediatrics].

PMID- 8143182
TI  - [Advances in oromaxillofacial surgery].

PMID- 8143183
TI  - [Advances in otorhinolaryngology].

PMID- 8143184
TI  - [Advances in dermatology].

PMID- 8143185
TI  - [Advances in psychiatry].

PMID- 8143186
TI  - [Advances in laboratory diagnosis].

PMID- 8143187
TI  - [Advances in radiology].

PMID- 8143188
TI  - [Advances in ultrasonics].

PMID- 8143189
TI  - [Advances in pathology].

PMID- 8143190
TI  - [Advances in nuclear medicine].

PMID- 8143191
TI  - [Advances in geriatrics].

PMID- 8143192
TI  - [Advances in medical genetics].

PMID- 8143193
TI  - [Nested-polymerase chain reaction in detection of Helicobacter pylori in human
      dental plaque].
AB  - A nested polymerase chain reaction (N-PCR) for the specific detection of
      Helicobacter pylori (H. pylori) was developed with two primer pairs derived from
      the urease gene A of H. pylori. The N-PCR was used to detect all 21 H. pylori
      strains, including 20 clinical isolates and 1 reference strain (NCTC 14126), but
      failed to detect 12 other bacterial species. It was shown that the PCR assay is
      100% specific. Tenfold serial dilution experiments revealed that N-PCR could
      detect as little as 0.1 fg DNA. Samples of dental plaque and stomach biopsies
      from 29 patients were collected. Gastric specimens were tested by N-PCR, and the
      results were compared with those of culture, urease test and histological
      examination (reference standard). H. pylori sequences were detected by PCR
      showing that 21 were positive. The dental plaque samples from 8 of the 21
      patients who tasted positive of gastric biopsies were positive by N-PCR. However,
      none of 8 dental plaque samples from the patients whose gastric samples were
      negative showed amplification. Dual therapy was given to two patients who were H.
      pylori positive in gastric mucosa and dental plaque. One month after treatment,
      H. pylori was eradicated from the gastric mucosa, but persisted in dental plaque.

PMID- 8143194
TI  - [Segregation ratio and heritability of lung cancer in Xuanwei County, China].
AB  - To determine the relation between genetic factor and lung cancer We selected 370
      lung cancer probands in Xuanwei county, Yunan Province China. The data on 370
      nuclear families were analysed. The segregation ratio of lung cancer was 0.15 and
      the genetic model of lung cancer belonged to polygenetics. The heritability of
      lung cancer was 24.6%, 14.6% for male and 37.8% for female. It is concluded that
      genetic factor is one of the risk factors for lung cancer is specially of
      importance for females, but it is not a main risk factor for lung cancer. Our
      results are helpful in complaining the high incidence of lung cancer in females
      in Xuanwei county.

PMID- 8143195
TI  - [Urine levels of soluble interleukin 2 receptor and free light chain
      immunoglobulins in lupus nephritis].
AB  - To find out the relationship between soluble interleukin 2 receptor (sIL-2R) or
      free light chain immunoglobulins (FLCI) and the activity of lupus nephritis (LN),
      we determined sIL-2R by ELISA and FLCI by immunodiffusion in the urine of 30
      patients with LN and 20 normal persons. We also studied the correlation of sIL-2R
      levels with clinical and serologic findings over 3 months in the patients. sIL-2R
      was significantly higher in the active LN patients (160 +/- 108U/ml) than in the
      normal controls (85 +/- 19U/ml, P < 0.01) and in the inactive LN patients (92 +/-
      23 U/ml, P < 0.05), but their serum complements did not change significantly. The
      positive rate of urine FLCI was higher in the active LN patients than in the
      inactive LN patients (77% to 15%, P < 0.01) and the normal controls (negative).
      These results suggest that the urine sIL-2R and FLCI are sensitive markers for
      disease activity in LN.

PMID- 8143196
TI  - [Retained copper needles for the treatment of cavernous hemangioma].
AB  - 8 cases of huge cavernous hemangioma (3 in hand, 2 in lip and buccal region, 1 in
      perineum and buttock and 2 in frontal region) were treated by retaining copper
      needles which were inserted into the blood-filled spaces and feeders with
      satisfactory results. Preparation of copper needles, the technique of insertion
      of needles, duration of treatment, local and systemic reactions after the
      treatment are described.

PMID- 8143197
TI  - [Therapeutic effect of local injection of corticosteroid hormone in the treatment
      of hemangioma in childhood and infancy].
AB  - Hemangioma is a common disease in infancy and childhood. From January, 1987 to
      January, 1992, the author had treated 11 out-patients of infants and children
      suffering from hemangioma with local injections of corticosteroid hormone and
      obtained an effective rate of 87.8% and cure rate of 51.2%. During the clinical
      observation, the author found that after injection, the hemangioma disappeared
      quickly without recurrence, infection, drug-induced side effects and other
      complications. It is considered that a mixture of corticosteroids is the first
      choice for local injection for the treatment of hemangioma in infancy and
      childhood. It is safe, effective and simple.

PMID- 8143198
TI  - [Restoration of opponens function with transplantation of free composites dorsal
      pedal skin flap containing m. extensor hallucis brevis].
AB  - Since 1983, we have used free dorsal pedal flaps with m. extensor hallucis brevis
      for two patients with serious thenar defects to restore their thumb function. The
      results were satisfactory, as most of oponens function was restored, however the
      power of the thumbs was inadequate. Functional restoration of the thumb after the
      loss of thenar muscles involves many aspects of microsurgery. This article
      discusses only the dissection of the muscle, the orientation of transferred
      muscle, etc.

PMID- 8143199
TI  - [Reconstruction of hand wound with skin flap containing supracarpal cutaneous
      branch of ulnar artery].

PMID- 8143200
TI  - [Reconstruction of external ear with double-lobe skin flap].
AB  - The authors reconstructed the external ear and external auditory canal in fifty
      patients using double-lobe skin flap and three-point landmark method. After
      operation the new auricle is natural in appearance and correctly located. The
      hearing ability is increased in a part of patients. This article describes the
      method and main features of the operation.

PMID- 8143201
TI  - [Allogeneic auricular cartilage framework for total reconstruction of the ear in
      8 patients].
AB  - This paper reports our experience in total reconstruction of the ear using
      allogeneic auricular cartilage framework in 8 patients. The allogeneic auricular
      cartilage framework has natural appearance, and no carving or fabrication is
      needed. The cartilage treated with glutaraldehyde firmly adhered to its
      surrounding tissue of the host in a short time. Good results were observed in 6
      month to 2-year follow-up, and no complications such as rejection, distortion and
      absorption occurred.

PMID- 8143202
TI  - [Microcirculation through a window on skin flap].

PMID- 8143203
TI  - [Experimental study of circulation of skin flap with subdermal vascular network].

PMID- 8143204
TI  - [Anatomic basis and clinical application of retrograde axial skin flap].
AB  - This study is an analysis of anatomic basis and clinical application of
      retrograde axial skin flap. The arterial supply of retrograde axial skin flap was
      classified into three types: (1) Arcuate artery; (2) Circular artery; (3)
      Arterial anastomosis branch. The venous return of retrograde axial skin flap was
      also divided into three types: (1) No venous valve; (2) Weak venous valve; (3)
      Venous anastomosis branch. 35 cases of soft tissue defect were repaired by
      retrograde axial skin flaps. The sizes of the flaps ranged from 4 x 2 cm to 18 x
      7 cm. All flaps survived with satisfactory results. Advantages and disadvantages,
      the donor area, the selection of vascular pedicle, and the precautions in the
      preparation of this flap were discussed.

PMID- 8143205
TI  - [Treatment of accessory nerve injury].
AB  - From 1975 through 1988, 11 cases with accessory nerve injury were admitted to our
      hospital. The etiology in 9 of these cases was inadvertent surgical injury during
      operation. In the other 2 cases it was injured in accidents. The typical clinical
      manifestations of paralysis of the trapezius muscle and disorder of the shoulder
      movement were all seen in our cases. The diagnostic features, indications for
      operation, surgical technics and criteria for efficacy assessment were discussed.
      The necessity of early operation was stressed, and either neurorrhaphy or
      neurolysis should be done.

PMID- 8143206
TI  - [1-stage repair of congenital blepharostenosis].
AB  - Nine cases of congenital blepharostenosis have been corrected by operation. The
      procedure included shortening of the ligaments of the inner canthus, correcting
      epicanthus, incision of the external canthus, and rectifying drooping of the
      upper lid in one stage. After operation, incision scar is not noticeable.

PMID- 8143207
TI  - [Blepharoplasty and oculocardiac reflex].
AB  - 100 patients have undergone electrocardiograph before and during blepharoplasty
      and after anaesthesia. The results show that the positive rate of oculocardiac
      reflex is 65%. The mechanism of occurrence of oculocardiac reflex is analysed. It
      has also been pointed out that great attention should be paid to the phenomenon
      and appropriate measures should be taken to prevent the occurrence of
      oculocardiac reflex.

PMID- 8143208
TI  - [Early repair of cleft palate in children. Report of 13 cases].
AB  - Thirteen cases of early repair of cleft palate in children are reported. The
      average age is 15 months. No anesthetic or early post-operative complications
      occurred. Follow-up examinations found the results satisfactory in 70% of the
      cases. The optimum age for repair, the relationship between the time of repair
      and effects on phonation, and the question of whether early repair would affect
      the growth of the palate are discussed in this paper.

PMID- 8143209
TI  - [Oxygen free radical injury after delayed fluid resuscitation in burn patients].
AB  - Sixty seven burn patients (TBSA > 30%) were entered in a prospective study. Among
      them, twenty seven experienced delayed fluid resuscitation (DFR group) and the
      rest had early resuscitation (non-DFR group). Oxygen free radical (OFR) content
      in the blood was measured with ESR technic, and levels of blood SOD, blood GSHpx,
      serum MDA were also determined. The results showed: 1 The morbidity and mortality
      of burn shock and MSOF were higher in DFR group as compared with non-DFR group. 2
      There was a significant increase of blood OFR content subsequent to resuscitation
      in DFR group as compared with that in non-DFR group. 3 The level of MDA in the
      serum of patients with burn shock was higher in DFR group than that in non-DFR
      group. 4 In DFR group, the level of serum MDA is higher in patients who developed
      MSOF as compared with that in patients who did not develop MSOF. The data
      indicated that DFR augmented the morbidity and mortality of burn shock and MSOF,
      in which OFR might play a role.

PMID- 8143210
TI  - [Application of tissue pressure measurement in circumferential burn of limb].

PMID- 8143211
TI  - [Injury score for deep burns--(1) Structure and functions of extremity].
AB  - The investigation of the structure, functions and functional loss ratio of the
      burn injuries was carried out in twelve cross sections of the extremities in this
      paper. The basic structure-function constants of the vessel, nerve, tendon,
      muscle, bone joint capsule and ligament were obtained from the investigation and
      converted into index. We hope that the index would provide a reliable numerical
      indication system for the early diagnosis and repair of the deep burn injuries.

PMID- 8143212
TI  - [Effect of arginine supplementation on T-lymphocyte function in burn patients].
AB  - It is well accepted that nutritional support improves the immunologic functions
      in burn patients. Arginine has been demonstrated to have tissue--specific
      properties which influence certain components of the immune system. A series of
      experiments were carried out in this study, in order to evaluate the immune
      effect of arginine on T lymphocyte functions in burn patients. Two groups of burn
      patients with comparable clinical protocol receiving same nutritional
      administration except the amount of arginine in the nutrients were studied. In
      one group, 2% of energy supplied by arginine was added in their nutrients, while,
      the control group received 2% of energy from amino acid compounds instead. The T
      lymphocyte immune parameters were determined on days 3, 7, 14, 21 and 28
      postburn. The data showed that the 2% of total energy supplied by arginine was
      found to significantly enhance the T lymphocyte response to PHA, CD4 phenotype
      expression, CD4/CD8 ratio, IL-2 production and IL-2 receptor expression, as
      compared with the control group. It suggests arginine should become one of the
      most important nutrients supplied to burn patients.

PMID- 8143213
TI  - [Influence of burn shock on the prognosis of burn wound sepsis in mice].
AB  - The influence of burn shock on the prognosis of burn wound sepsis was
      investigated in mice. Mice with full-thickness burn of 13% TBSA was injected
      subcutaneously under the burned area immediately after burning with 0.2ml P.
      aeruginosa (1 x 10(3)CFU/ml) or 0.2 ml K. pneumoniae (5 x 10(3)CFU/ml). The
      survival rate in P. aeruginosa burn wound sepsis was 49% in resuscitation group
      (n = 53) on 7 postburn day and 17% in non-resuscitation group (n = 24) (P <
      0.01). The mean survival time in dead mice of resuscitation group (n = 27) was
      4.2 +/- 1.7 days and 2.5 +/- 0.6 days in that of non-resuscitation group (n = 20)
      (p < 0.01). The survival rate in K. pneumoniae burn wound sepsis was 69% in
      resuscitation group (n = 26) on 7 postburn day and 15% in non-resuscitation group
      (n = 13) (P < 0.01). The mean survival time in dead mice of resuscitation group
      (n = 8) was 5 +/- 1.35 days and 2.1 +/- 0.3 days in that of non-resuscitation
      group (n = 11) (p < 0.01). These results indicated that burn shock might increase
      the mortality of burn wound sepsis and resuscitation could improve the prognosis
      of burn wound sepsis.

PMID- 8143214
TI  - [Cultivation of cicatricial fibroblasts and kinetics of growth].
AB  - The fibroblasts from normal skin, hypertrophic scar and keloid were cultured in
      vitro and their growth property was compared. The results showed that there was
      similar density-dependent inhibition in these three strains, and there were no
      morphological differences among them. But, in normal skin, fibroblasts were
      parallelly arranged, showing "fingerprint" and marked polarization, while that in
      hypertrophic scar and keloid presented crisscross and overlapping with less
      polarization. All of three strains had same growth kinetics, i.e. the cell growth
      curve, DNA synthesis and mitosis index were similar during their logarithmic
      phase.

PMID- 8143215
TI  - [Applied anatomic study of the posterior interosseous artery in forearm].
AB  - The posterior interosseous artery (PIA) is the nutritive artery of the dorsal
      forearm flap. This article describes the dissection study for PIA in 40 cases.
      The results are as follows: 1. PIA is classified into different types; 2. the
      external diameter of PIA at the inferior margin of the supinator, the length of
      PIA and the distance between the artery and external epicondyle of the humerus
      are described; 3. the course of the artery and its neighboring structures are
      defined. The above study provides the foundation of designing of the posterior
      forearm pedicled flap in the repair of defects situated on the forearm and hand.

PMID- 8143216
TI  - [Silicone gel in the treatment of burn and prevention of hypertrophic scar].

PMID- 8143217
TI  - The governments' decision on tobacco smuggling: a potential disaster.

PMID- 8143218
TI  - Canadian heart health care--product and cost.

PMID- 8143219
TI  - Continuous wave Doppler measurements of aortic bloodflow during exercise in
      patients with chronic heart failure.
AB  - OBJECTIVE: To assess the feasibility of obtaining continuous wave Doppler
      measurements of aortic bloodflow from the suprasternal notch during upright
      treadmill exercise as an objective adjunct to cardiac performance and functional
      capacity in heart failure. DESIGN: Prospective descriptive study. SETTING:
      University teaching hospital out-patient heart failure clinic. PATIENTS: Fifty
      three patients with New York Heart Association (NYHA) class II or III heart
      failure (left ventricular ejection fraction 9 to 37%) and 15 control subjects of
      similar age but without heart disease. INTERVENTION: Symptom-limited (or to
      completion of 22-min protocol) treadmill exercise using a modified Naughton
      protocol. RESULTS: Exercise duration was 11.3 +/- 0.6 mins for heart failure and
      20.5 +/- 0.6 mins for normals. Both within subject and interobserver variability
      for the Doppler derived variables were satisfactory. There were no significant
      differences at rest between groups for any of the measured Doppler variables. In
      heart failure patients compared with normals, significant reductions in stroke
      distance and peak velocity occurred during stage I and in peak acceleration
      during stage II and persisted throughout exercise with reductions in maximum
      achieved peak velocity (0.64 +/- 0.02 versus 0.97 +/- 0.05 m/s, P < 0.001), peak
      acceleration (19.0 +/- 0.9 versus 37.3 +/- 2.4 m/s2, P < 0.001) and stroke
      distance (7.5 +/- 0.3 versus 11.2 +/- 0.6 cm, P < 0.001). Receiver operator
      curves had very favourable discriminating characteristics. No significant
      differences in Doppler indices were observed between patients due to etiology of
      heart failure or NYHA functional class. CONCLUSION: Aortic bloodflow indices can
      be reliably measured from the suprasternal notch during upright treadmill
      exercise in the majority of heart failure patients. Since the indices were
      abnormal even at very early stages of exercise, further studies are required to
      define their usefulness as an adjunct in the assessment of heart failure patients
      whose maximum exercise tolerance is limited by other factors such as arthritis,
      intermittent claudication or lung disease.

PMID- 8143220
TI  - Sotalol in patients with implanted automatic defibrillators: effects on
      defibrillation and comparison with amiodarone.
AB  - OBJECTIVES: Although many patients receiving implanted cardioverter
      defibrillators receive concomitant antiarrhythmic therapy, the risks and benefits
      of different agents for such patients are not well understood. It was
      hypothesized that sotalol, a drug with beta-blocking and class II antiarrhythmic
      properties would be useful in these patients. DESIGN: Nonrandomized prospective
      cohort study of the effects of sotalol versus other antiarrhythmic therapy on
      defibrillation energy requirements. SETTING: Tertiary care referral centre.
      PATIENTS: Patients referred for management of life threatening ventricular
      arrhythmia in whom an implanted cardioverter defibrillator was indicated on
      standard clinical grounds. INTERVENTIONS: Intraoperative testing of
      defibrillation energy requirements, exercise testing, electrophysiological
      testing. MAIN RESULTS: Fifteen patients were treated with oral sotalol (173.3 +/-
      59.8 mg/day). Sotalol blunted maximal heart rate during treadmill exercise (120.9
      +/- 29.9 beats/min). Mean right ventricular effective refractory period increased
      from 251.7 +/- 21.7 to 276.7 +/- 25.7 ms (P = 0.05). All patients received one
      large (28 cm2) and one small (14 cm2) epicardial electrode patch. The lowest
      energy to defibrillate successfully from induced ventricular fibrillation (VF)
      was 5.9 +/- 3.7 J (median 4.1 J), with all patients defibrillated at 15 J or
      less. In a concurrent comparison group of 16 similar patients not treated with
      sotalol (13 on amiodarone and three on beta-blockers), with identical or larger
      patch size, and identical placement, the lowest successful energy to defibrillate
      from induced VF was significantly higher (16 +/- 8.8 J) (P < 0.05). Mean cycle
      length of VF from intracardiac recordings was 232 +/- 37 ms, and was
      significantly inversely correlated with lowest successful energy (r = 0.61, P <
      0.05). CONCLUSIONS: Oral sotalol may be useful in conjunction with an automatic
      defibrillator; it is associated with low defibrillation energy requirements in
      humans, and may alter VF.

PMID- 8143221
TI  - Effects of oxygen free radicals and scavengers on the cardiac extracellular
      collagen matrix during ischemia-reperfusion.
AB  - OBJECTIVE: Collagen is lysed early during ischemia-reperfusion, but whether this
      is due to ischemia or reperfusion injury is not known. The effect of oxygen free
      radicals and free radical scavengers on left ventricular hemodynamics, myocardial
      morphology and collagen content were studied in an isolated, Langendorff-perfused
      rat heart model of regional ischemia-reperfusion. METHODS: All hearts received
      left anterior descending coronary artery ischemia for 20 mins. Group 1 had
      ischemia only; group 2 had ischemia followed by reperfusion with oxygenated Krebs
      Henseleit buffer for 20 mins; group 3 had oxygen free radicals generated by
      hypoxanthine and xanthine oxidase during reperfusion; group 4 had free radical
      scavengers with superoxide dismutase plus catalase; group 5 had both oxygen free
      radicals and free radical scavengers during reperfusion. RESULTS: Left
      ventricular developed pressure decreased significantly in group 3 during ischemia
      followed by reperfusion (58 +/- 3.1 mmHg versus 42 +/- 2.4 mmHg, P = 0.004), but
      did not change significantly in any of the other groups. Necrosis score on
      pathology was highest in group 3; this score also was higher than that in group 5
      with free radical scavengers added (3.0 +/- 0.3 versus 2.0 +/- 0.4, P = 0.07) and
      higher than that of group 2 with reperfusion with buffer only (3.0 +/- 0.3 versus
      1.4 +/- 0.5, P < 0.05). Collagen content decreased significantly compared with
      control in group 3 only with ischemia followed by reperfusion with the addition
      of oxygen free radicals (18.4 +/- 1.5 versus 11.9 +/- 1.7 g/mg protein, P <
      0.05). The addition of free radical scavengers in group 5 mainly attenuated the
      collagen loss. Scanning electron microscopy revealed profound structural changes
      of the extracellular collagen matrix in numerous regions of 'stunning'
      independent of tissue necrosis. CONCLUSIONS: We conclude that: first, oxygen free
      radicals trigger significant collagen damage and left ventricular dysfunction
      during reperfusion; second, these changes extend beyond the ischemic damage
      alone; and third, free radical scavengers can effectively limit oxygen free
      radical-induced collagen loss and left ventricular dysfunction.

PMID- 8143222
TI  - Structural remodelling in heart failure: gelatinase induction.
AB  - OBJECTIVE: Rapid ventricular pacing in the dog produces severe congestive cardiac
      failure in association with neurohumoral activation and marked depression of
      cardiac function. This syndrome is associated with left ventricular dilation,
      significant wall thinning, assumption of a more globular shape and disruption of
      the cardiac collagen infrastructure, given that the fibrillar collagen network is
      a major determinant of cardiac architecture. The purpose of the present study was
      to investigate whether there was evidence of increased activity of matrix
      metalloproteinases. The authors speculated that it could play an important
      permissive role in myocyte realignment, thereby resulting in the changes in
      cardiac size and shape. DESIGN: Twenty-one male mongrel dogs underwent
      ventricular pacing and were allocated into one of three groups: early heart
      failure (n = 6), severe heart failure (n = 7) and recovered heart failure (n =
      8). Measurements included echocardiographic and hemodynamic parameters, plasma
      noradrenaline levels, left ventricular noradrenaline levels and matrix
      metalloproteinase activity. RESULTS: The study showed gelatinase activity present
      in normal left ventricular tissue predominantly attributable to a 72 kDa
      gelatinase (85%) and, to a much lesser extent, by a 92 kDa gelatinase (15%).
      Levels of 92 kDa gelatinase increased slightly within one week and reached
      maximal levels with severe heart failure, where it represented over one-half of
      the total gelatinase activity. In animals allowed to recover for four weeks, 92
      kDa gelatinase decreased significantly to approximately 50% of the levels
      observed at severe heart failure. The levels of 72 kDa gelatinase did not change
      significantly during any experimental condition. Significant correlations between
      92 kDa percentage activity and systolic and diastolic left ventricular areas
      across all time-points were evident (r = 0.59 and 0.63, respectively, P < 0.05
      for both). CONCLUSION: The association of 92 kDa gelatinase with changes in left
      ventricular area suggests a possible modulating role for this matrix
      metalloproteinase in disruption of the fibrillar components of the left
      ventricular extracellular matrix.

PMID- 8143223
TI  - Antioxidant status of Japanese quail: comparison of atherosclerosis-susceptible
      and -resistant strains.
AB  - OBJECTIVE: To compare levels of antioxidant components of blood and aortic tissue
      from two strains of Japanese quail showing high and low susceptibilities to
      atherosclerosis and receiving either control or cholesterol-enriched diets.
      ANIMALS: All experimental birds were placed on the control diet until eight weeks
      of age. Twenty males of each strain were then placed on the atherogenic diet
      (control diet supplemented with 1% cholesterol) and another 20 males of each
      strain were continued on the control diet for an additional 10 weeks. MAIN
      RESULTS: In the absence of cholesterol supplementation, plasma cholesterol and
      triglyceride and antioxidant enzyme profiles of aorta, red blood cells and plasma
      were comparable in the two groups of birds, with the exception of a small, but
      significant (P < 0.05), decrease in aortic glutathione reductase in susceptible
      animals (0.378 nmol/min/mg) relative to the resistant birds (0.441 nmol/min/mg).
      Cholesterol feeding produced larger increases in cholesterol and triglycerides
      and more extensive atherosclerotic plaque formation in susceptible compared with
      resistant quail. In the susceptible group, significant negative correlations were
      noted between severity of atherosclerotic lesions and aortic superoxide dismutase
      (correlation coefficient -0.752) and glutathione reductase (correlation
      coefficient -0.775) activities. Cholesterol feeding was associated with increased
      activity of plasma glutathione peroxidase and superoxide dismutase activities in
      both strains, although only the susceptible birds showed significant positive
      correlations of superoxide dismutase activities with plasma cholesterol
      (correlation coefficient +0.694) and triglycerides (correlation coefficient
      +0.669). Peroxide-induced depletion of glutathione in red blood cells was
      unaffected by cholesterol feeding, although red blood cell susceptibility to
      lipid peroxidation was decreased to an equivalent degree in both strains.
      CONCLUSIONS: Susceptible and resistant quail are biochemically distinct in terms
      of alterations in antioxidant components produced by dietary cholesterol
      supplementation. Results of the present study are consistent with the proposed
      involvement of oxidative processes in the pathogenesis of atherosclerosis.

PMID- 8143224
TI  - Postnatal maturation of baroreflex heart rate control in neonatal swine.
AB  - OBJECTIVE: Despite extensive knowledge about basic baroreceptor function, there
      continues to be controversy as to whether there is postnatal maturation of the
      cardiovascular baroreflex. DESIGN/ANIMALS: Acutely studied postnatal
      developmental changes in baroreflex sensitivity with a neonatal porcine model in
      28 chloralose-anesthetized piglets from birth to six weeks of age. INTERVENTIONS:
      Steady-state heart rate versus blood pressure response curves were generated by
      altering blood pressure with increasing doses of phenylephrine or nitroprusside.
      Data were fitted to the Hill equation for sigmoidal curves, and the maximum heart
      rate, maximum slope (sensitivity) and blood pressure at 50% maximal heart rate
      (P50) were calculated. MAIN RESULTS: Baroreflex sensitivity was found to increase
      from birth to six weeks of age (P < 0.0001), with the most rapid changes
      occurring after two weeks of age. Increasing age was accompanied by shift of the
      baroresponse curve to an increased range of heart rate changes at higher blood
      pressures. Maximal heart rates did not differ with advancing postnatal age.
      CONCLUSIONS: Swine baroreflex sensitivity increases from birth to six weeks of
      age, with higher blood pressures causing greater bradycardia in older piglets.
      These findings are consistent with postnatal maturation of the cardiovascular
      autonomic nervous system.

PMID- 8143226
TI  - Effect of cardiac filling pressures on the release of atrial natriuretic peptide
      during exercise in heart transplant recipients.
AB  - OBJECTIVE: To determine the influence of body posture and central hemodynamics on
      the plasma levels of immunoreactive atrial natriuretic peptide (irANP) during
      exercise in cardiac transplant patients. METHODS: Central hemodynamics, mixed
      expired gas and ventilatory measurements, and venous blood sampling (for irANP
      determination) were obtained in cardiac transplant patients at rest and during
      supine (n = 12) or upright (n = 12) graded cycle exercise. Cardiopulmonary and
      irANP responses to exercise were compared between the upright and supine
      postures. RESULTS: At rest (supine), irANP concentrations were similar in both
      groups (172 +/- 87 pg/mL supine and 182 +/- 72 pg/mL upright) and did not
      correlate with resting supine central hemodynamics. During exercise, central
      filling pressures increased in both groups but patients exercising in the supine
      position had a greater increase. Peak exercise right atrial pressure was 12 +/- 4
      mmHg supine versus 7 +/- 5 mmHg upright (P < 0.005). Peak exercise pulmonary
      capillary wedge pressure was 22 +/- 6 mmHg supine versus 14 +/- 5 mmHg upright (P
      < 0.005). At peak exercise, irANP levels were greater in the supine than upright
      position (419 +/- 166 pg/mL supine versus 277 +/- 40 pg/mL upright, P < 0.05).
      The change in irANP from rest to peak exercise correlated (P < 0.05) with changes
      in pulmonary capillary wedge pressure (r = 0.67), systolic pulmonary artery
      pressure (r = 0.78) and right atrial pressure (r = 0.53). There was, however, no
      correlation between change in irANP and peak oxygen consumption, change in heart
      rate or change in mean arterial blood pressure. CONCLUSIONS: In cardiac
      transplant recipients, exercise is a stimulus for ANP secretion, and augmentation
      in plasma irANP levels during exercise is modulated by changes in central
      hemodynamics.

PMID- 8143225
TI  - Sex differences in the use of invasive coronary procedures in Ontario.
AB  - OBJECTIVE: To determine whether sex differences exist in the use of coronary
      angiography, coronary artery bypass surgery (CABS) or percutaneous transluminal
      coronary angioplasty (PTCA) among persons recently diagnosed with an acute
      myocardial infarction (AMI) in Canada. BACKGROUND: A growing body of literature
      suggests that coronary artery disease in males is treated differently from
      females. Specifically, recent studies have indicated that sex may influence
      decisions about the use of invasive diagnostic and therapeutic coronary
      procedures in patients with suspected or proven coronary artery disease. PATIENTS
      AND METHODS: The study design is a population-based inception cohort study. The
      data source is hospital discharges from all acute care hospitals in Ontario. The
      study population consisted of 6949 men and women discharged with a principal
      diagnosis of AMI between April 1 and September 30, 1990, and followed through
      record linkage until March 31, 1991 to determine whether any invasive coronary
      procedures were performed after their AMI. Odds ratio estimates (OR) and 95%
      confidence intervals (95% CI) for use of coronary angiography, CABS and PTCA in
      men were compared with those in women. RESULTS: The adjusted OR for coronary
      angiography was 1.4 (95% CI 1.2 to 1.6), indicating that males were more likely
      to undergo angiography than females. A similar finding was seen for CABS (OR =
      1.6, 95% CI 1.2 to 2.1), but for PTCA, the sex difference was less pronounced (OR
      = 1.3, 95% CI 1.0 to 1.7). Cox proportional hazards regression also was used to
      test the hypothesis and showed similar results. CONCLUSIONS: Women suffering AMI
      undergo coronary angiography and CABS at a significantly lower rate than men in
      Ontario, with similar trends evident in use of PTCA.

PMID- 8143227
TI  - Atrioventricular nodal reentrant tachycardia in patients with ventriculo-atrial
      conduction block.
AB  - OBJECTIVE: To demonstrate the reversibility of retrograde ventriculo-atrial block
      by isoproterenol in patients with atrioventricular nodal reentrant tachycardia
      (AVNRT). DESIGN: Three case reports and their electrophysiological features.
      PATIENTS: Three patients with documented or suspected paroxysmal supraventricular
      tachycardia. INTERVENTIONS: At routine electrophysiology study, no
      supraventricular tachycardia was inducible in the baseline state. Infusion of
      isoproterenol (1 to 5 micrograms/min) was given and stimulation procedures were
      repeated. RESULTS: At baseline, all three patients had discontinuous antegrade
      atrioventricular (AV) nodal conduction, but very poor (two patients) or absent
      (one patient) ventriculo atrial conduction prevented induction of AVNRT. During
      infusion of isoproterenol, retrograde conduction was enhanced so that 1:1
      retrograde occurred to cycle lengths of 300, 340 and 260 ms. AVNRT was then
      inducible in all patients, reproducing their clinical symptoms. CONCLUSION:
      Absent or poor ventriculo-atrial conduction in patients with suspected AV node
      reentry does not preclude the development of tachycardia with sympathomimetic
      enhancement. Isoproterenol should be given to attempt reversal of retrograde
      block in these patients.

PMID- 8143228
TI  - Prognostic implications of transient left ventricular cavitary dilation during
      exercise and dipyridamole-thallium imaging.
AB  - OBJECTIVE: To determine the prognostic implication of exercise and dipyridamole
      induced transient left ventricular cavitary dilation (TLVD). DESIGN: TLVD was
      observed and a follow-up obtained in 61 patients after exercise and in 62
      patients following dipyridamole infusion. PATIENTS: There was no statistical
      difference between groups in terms of sex, history of hypertension, diabetes,
      renal failure, previous myocardial infarction, severity of angina syndrome,
      congestive heart failure, resting electrocardiographic (ECG) abnormalities,
      clinical or ECG signs of ischemia during stress, number of reversible perfusion
      defects on thallium images or duration of follow-up (21 months). RESULTS:
      Dipyridamole patients were slightly older (64 versus 57 years) and displayed more
      thallium redistribution (P = 0.002). After a mean follow-up of 21 months, both
      fatal and nonfatal (myocardial infarction or cardiac death) cardiac events were
      more frequent in the dipyridamole group (50% versus 9%, P = 0.0001). CONCLUSIONS:
      Patients with dipyridamole-induced TLVD are at greater risk than those with
      exercise-induced TLVD at the authors' institution.

PMID- 8143229
TI  - Intra-atrial course of the right coronary artery and its branches.
AB  - OBJECTIVE: To illustrate and describe an anomaly of right coronary artery (RCA)
      course. SETTING: Postmortem examination of cardiac tissue. DESIGN AND PATIENTS:
      Three cases where the RCA had an intracavitary position in the right atrium are
      described. Additionally, light microscopic analysis of random sections of
      posterior right atrium from 100 consecutive autopsy cases was undertaken. MAIN
      RESULTS: Each of the index cases was an incidental finding at autopsy. In two
      cases, the RCA, after passing the acute angle of the heart (epicardially),
      entered the right atrium posteriorly and ran subendocardially for distances of
      1.5 and 3.0 cm, respectively. In the third case, the RCA entered the right atrial
      cavity 2.5 cm from its origin and ran subendocardially for 2.0 cm. In all three
      cases, the RCA exited the atrial cavity and once again attained an epicardial
      course. In the first two cases, the RCA ran 1.0 cm above the atrioventricular
      groove, rather than in its normal location at the annulus. The random sections of
      right atrial wall showed that medium calibre arterial branches of the RCA also
      commonly run in subendocardial positions (29 of 100 cases) and sometimes project
      into the atrial cavity (five of 29 cases). CONCLUSIONS: The genesis of this
      epicardial coronary anomaly is unclear, but may relate to the 'higher' than
      normal course of the artery in these cases, in concert with the normal thinness
      of the right atrial wall, and the tendency for even medium calibre arteries to
      assume this subendocardial location. Despite the benign outcome of the index
      cases described here, the authors believe that this intracavitary course of the
      RCA could pose special technical problems during coronary artery catheterization
      and bypass grafting.

PMID- 8143230
TI  - Endothelium-derived relaxing factor participates in the transmural distribution
      of coronary bloodflow.
AB  - OBJECTIVE: To study the role of endothelium-derived relaxing factor (EDRF)--which
      participates in the regulation of coronary vascular tone, but has an unknown role
      in the transmural distribution of coronary flow--in transmural coronary flow
      distribution during steady basal flow and during reactive hyperemia in the left
      ventricular wall of the dog. DESIGN: Sixteen mongrel dogs of either sex weighing
      between 14 and 24 kg were anesthetized with sodium pentobarbital. The lungs were
      mechanically ventilated and the thoraces were opened. Circumflex coronary flow
      was measured with an electromagnetic flowmeter, and its transmural distribution
      across four layers of the left ventricular wall was measured with radioactive
      microspheres. Measurements were done during steady basal flow and during peak
      reactive hyperemia before and after the inhibition of the EDRF synthesis with N
      omega-nitro-L-arginine (NNLA). Mean aortic and systolic left ventricular
      pressures and heart rate were kept constant, and left ventricular end-diastolic
      pressure increased by only 3.3 mmHg during reactive hyperemia. MAIN RESULTS: NNLA
      produced a mean decrease of steady basal flow of 22.3 +/- 0.9% (P < 0.01). Flow
      decreased in all layers of the wall; the decrease, however, was proportionally
      less in the subendocardium (P < 0.05). During reactive hyperemia (before NNLA),
      flow was redistributed to the subendocardium (compared with steady basal flow).
      Administration of NNLA reduced the magnitude of peak reactive flow to all layers
      in the wall, showing a relative enhancement of flow in the subendocardium.
      CONCLUSIONS: These results suggest that the EDRF participates in the regulation
      of coronary bloodflow and its distribution across the left ventricular wall.

PMID- 8143231
TI  - Cardiac tamponade as the initial presentation of papillary thyroid carcinoma.
AB  - Hypothyroidism is a well known cause of pericardial effusions and cardiac
      tamponade; thyroid carcinoma metastatic to the heart and pericardium is rarely
      encountered in clinical practice. The authors report the case of a 68-year-old
      male who presented in acute distress from cardiac tamponade. Cytological
      examination of the pericardial and pleural fluid, and histological examination of
      a pericardial biopsy revealed a metastatic papillary carcinoma with psammoma
      bodies. Subsequent reexamination of the patient demonstrated a thyroid nodule and
      bilateral cervical lymphadenopathy. Fine needle aspiration of the thyroid nodule
      and cervical lymph nodes detected a papillary thyroid carcinoma with metastases
      to the lymph nodes. The literature relevant to hypothyroidism, thyroid malignancy
      and cardiac tamponade is briefly reviewed.

PMID- 8143232
TI  - Does endogenous zinc protoporphyrin modulate carbon monoxide formation from heme?
      Implications for long-term potentiation, memory, and cognitive function.
AB  - Carbon monoxide, which is formed endogenously from heme catabolism catalyzed by
      heme oxygenase and shares some of the chemical and biological properties of
      nitric oxide, may play a similar role as a widespread signal transduction
      mechanism for the regulation of cell function and communication. Zinc
      protoporphyrin, an inhibitor of heme oxygenase, prevents induction of long-term
      potentiation. Zinc protoporphyrin is an endogenous substance and we suggest that
      it has a physiological role, by modulating heme oxygenase activity and,
      therefore, formation of carbon monoxide from heme. This in turn would modulate
      long-term potentiation, memory, and cognitive function.

PMID- 8143233
TI  - Isoproterenol antagonizes drug-induced prolongation of action potential duration
      in humans.
AB  - The effects of an isoproterenol infusion on the duration of the human right
      ventricular endocardial monophasic action potential at 90% repolarization were
      recorded in the absence and in the presence of an antiarrhythmic drug regimen
      containing class III effects in two similar groups of patients. The drugs used
      were amiodarone (N = 3, 300 +/- 50 mg), sotalol plus quinidine (N = 11, 156 +/-
      13 mg sotalol, 1688 +/- 594 mg quinidine), and sotalol alone (N = 3, 300 +/- 20
      mg). All patients had underlying coronary disease but no evidence of inducible
      ischemia. In the absence of antiarrhythmic drug, isoproterenol did not
      significantly change the relationship of action potential duration at 90%
      repolarization to cycle length; there was a linear decrease in action potential
      duration by 19.8% between a paced cycle length of 600 and 300 ms. Isoproterenol
      did not significantly shorten the action potential duration at any cycle length.
      However, isoproterenol decreased the ventricular effective refractory period at
      400 ms drive from 240 +/- 5.0 to 225 +/- 6.0 ms (p < 0.05) accompanied by no
      change in the ratio of refractory period to steady-state action potential
      duration. In the presence of class III drug effects, the action potential
      duration was increased by an average of 9.2% at all paced cycle lengths longer
      than 300 ms (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143234
TI  - Developmental changes in the gonadotropin releasing hormone neuron of the female
      rabbit: effects of tamoxifen citrate and pregnant mare serum gonadotropin.
AB  - Developmental changes in immunostained gonadotropin releasing hormone neurons
      were demonstrated in female rabbits assigned to the following treatment groups:
      (i) tamoxifen citrate, 10 mg.kg-1 x day-1, in sesame seed oil (vehicle) (n = 24)
      or (ii) vehicle alone (control, n = 24) for 108 days; and (iii) 50 IU of pregnant
      mare serum gonadotropin on postnatal days 22 and 25 (n = 24) or vehicle on
      nontreatment days. Treatments had no effect on the total number of immunostained
      cells, but there was a significant (p = 0.0160) developmental shift from cells
      with smooth processes to rough. Group comparisons revealed that there was a
      significant (p < 0.001) age-related increase in the number of rough cells in
      pregnant mare serum treated rabbits between days 25 and 75, indicating an
      advancement in the shift from smooth to rough cells. Plasma gonadotropin levels,
      ovarian follicular development, and the developmental shift from smooth to rough
      cells were markedly suppressed by tamoxifen treatment compared with rabbits of
      the control group, while no difference in estradiol levels were found. Our
      results suggest that a developmental shift in gonadotropin releasing hormone cell
      morphology from smooth to rough precedes sexual maturity in the female rabbit.

PMID- 8143235
TI  - Peripheral modulation of duodenal and colonic motility and arterial pressure by
      neuropeptide Y, neuropeptide Y fragment 13-36, peptide YY, and pancreatic
      polypeptide in rats: cholinergic mechanisms.
AB  - The pancreatic polypeptide-fold (PP-fold) peptides neuropeptide Y (NPY), peptide
      YY (PYY), and pancreatic polypeptide (PP) (500 pmol/kg) increased duodenal and
      colonic intraluminal pressure of urethane-anesthesized rats following intravenous
      (i.v.) bolus injections. Increases in mean arterial pressure (MAP) accompanied
      the excitatory effects of NPY and PYY on gastrointestinal motility in these rats
      during the same time period. Atropine attenuated PYY's excitatory effect on
      duodenal pressure of rats. Excitatory effects of NPY, PYY, and PP (i.v.) on rat
      colon were not mediated via the muscarinic receptors. In the presence of
      hexamethonium, a nicotinic antagonist, PP (i.v.) increased colonic pressure to a
      greater extent than when administered alone. This observation suggested that PP
      had an inhibitory effect on colonic motility, which was not apparent as a result
      of the larger excitatory component. The nicotinic antagonist did not modulate the
      effects of peripherally administered NPY or PYY on duodenal or colonic motility
      in anesthetized rats. The Y2 receptor ligand, NPY (13-36) (i.v.) (500 pmol/kg),
      increased duodenal and colonic pressure in rats to the same extent as the full
      NPY molecule. Therefore, the peripheral effect of PYY and NPY on duodenal and
      colonic motility in rats may be mediated via Y2 receptors. NPY and PYY (i.v.)
      initially increased MAP, which then return to baseline values. Unlike NPY and PYY
      (i.v.) which produced short-term hypertensive effects PP (i.v. decreased MAP.
      Atropine did not attenuate the hypertensive effects of PYY and NPY (i.v.);
      however, the hypotensive effect of PP (i.v.) was blocked by atropine. The effects
      of the PP-fold peptides on MAP were not altered in the presence of
      hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143236
TI  - Ethanol neuro-behavioural teratogenesis in the guinea pig: behavioural
      dysfunction and hippocampal morphologic change.
AB  - Ethanol neuro-behavioural teratogenesis was studied in the guinea pig because of
      its extensive prenatal brain development. Our objective was to study, in the
      offspring of the guinea pig, behavioural and hippocampal morphologic effects
      produced by chronic maternal administration of 3 and 4 g ethanol.kg body weight-1
      x day-1. Pregnant guinea pig received one of the following chronic treatments via
      intubation into the oral cavity: 3 or 4 g ethanol.kg-1 x day-1 as two equally
      divided doses 2 h apart: isocaloric sucrose and pair feeding; or water. Five
      litters were obtained for each treatment. Locomotor activity rate was determined
      on postnatal days 10, 20, and 60, and testing of the spontaneous alteration task
      was conducted beginning on postnatal days 22 and 62. After behavioural testing,
      the hippocampus of the brain of randomly selected guinea pig offspring of each
      treatment group was assessed histologically by light microscopic examination of
      cresyl violet stained coronal sections. The 3 and 4 g ethanol.kg-1 x day-1
      regimens did not restrict maternal body weight gain or growth of the offspring.
      Both regimens increased locomotor activity rate in the offspring, which persisted
      into adulthood for the 4 g ethanol.kg-1 x day-1 regimen. Neither ethanol regimen
      impaired spontaneous alternation, but the 4 g ethanol.kg-1 x day-1 regimen
      increased the percent completed trials. Only the 4 g ethanol.kg-1 x day-1 regimen
      produced structural injury in the hippocampus, consisting of a 25% decrease in
      the number of CA1 pyramidal neurons. The data demonstrate that the 4 g ethanol.kg
      1 x day-1 regimen produces more behavioural dysfunction and hippocampal
      morphologic change compared with the 3 g ethanol.kg-1 x day-1 regimen.

PMID- 8143238
TI  - Chronic leukotriene inhibition in the rat fails to modify the toxicological
      effects of a cyclooxygenase inhibitor.
AB  - A 5-week study was carried out in rats using a leukotriene biosynthesis inhibitor
      (MK-886; 3-[1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl]-2,2-
      dimethylpropanoic acid) at a dose of 300 mg.kg-1 x day-1, this being sufficient
      to produce > 90% inhibition of ex vivo leukotriene B4 synthesis in rat blood, and
      a cyclooxygenase inhibitor (indomethacin, 4 and 6 mg.kg-1 x day-1) to ascertain
      whether inhibition of leukotriene biosynthesis would potentiate or inhibit the
      toxicity associated with the administration of nonsteroidal anti-inflammatory
      drugs (NSAIDs), in particular the gastrointestinal damage. Treatment with
      indomethacin alone or in combination with MK-886 resulted in the toxicity
      normally associated with NSAIDs, including gastrointestinal lesions. No toxicity
      was associated with the administration of MK-886 alone, and MK-886 had no
      significant effect on the incidence of gastrointestinal lesions produced by
      indomethacin. These results indicate that leukotrienes are not significant
      mediators of NSAID-induced gastroenteropathy in the rat.

PMID- 8143237
TI  - Blood pressure normalization in carotid barodenervated rats: role of cardiac
      output.
AB  - This study evaluated the role of sympathetic nervous system (SNS) activity,
      peripheral hemodynamic changes, and pressure diuresis in blood pressure (BP)
      normalization in carotid barodenervated rats. The acute and short-term effects of
      carotid barodenervation or sham operation on blood pressure, heart rate, cardiac
      output, stroke volume, total peripheral resistance, and plasma catecholamine
      levels were determined. Changes in plasma volume, urine output, and water and
      food intakes were also measured. Surgical denervation of the carotid
      baroreceptors resulted in rapid rises in blood pressure and heart rate in
      anesthetized rats. These changes were associated with significant increases in
      plasma catecholamine levels and total peripheral resistance whereas the cardiac
      index and stroke volume remained unchanged. After recovery from the anesthesia,
      the blood pressure of carotid barodenervated rats was still significantly higher
      than that of sham-operated rats at 3 and 24 h after denervation and returned to
      sham-operated levels by 48 h. Plasma catecholamine levels and total peripheral
      resistance were higher in carotid barodenervated than in sham-operated rats on
      the 2 days following surgery. On the other hand, cardiac index (32 +/- 1 vs. 40
      +/- 2 mL.min-1 x 100 g-1 body mass) and stroke volume (205 +/- 13 vs. 283 +/- 4
      microL/beat) were significantly lower on day 2 in carotid barodenervated than in
      sham-operated rats, which suggests a compensatory role for carotid output in
      blood pressure normalization after carotid barodenervation. Both carotid
      barodenervation and sham operation caused a reduction in water and food intakes
      but the responses were greater in carotid barodenervated rats.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8143239
TI  - Myocardial response to regional ischemia and reperfusion in vivo in rat heart.
AB  - Ischemia-reperfusion-induced myocardial oxidative changes were investigated in
      open-chest hearts of anesthetized rats. Surgical occlusion of the left anterior
      descending coronary artery for 30 min followed by 15 min reperfusion resulted in
      a significant decrease of reduced glutathione, an increase in glutathione
      disulfide, and an enhanced lipid peroxidation in rapidly frozen left ventricular
      tissues. Direct electron paramagnetic resonance spectroscopy revealed an increase
      in free radical concentration in ischemic cardiac tissues reperfused for 45 s,
      but the increase diminished at 15 min. these alterations were associated with
      decreased activities of myocardial glutathione peroxidase, glutathione reductase,
      and catalase. Ischemia resulted in a significant reduction of high-energy
      phosphate compounds and an accumulation of nucleotide degradation products,
      particularly adenosine, in the myocardium. Deterioration of cardiovascular
      function in reperfused animals was also evident. It is concluded that regional
      ischemia followed by reperfusion in situ can produce biochemical and
      physiological alterations consistent with free radical injury in rat hearts, and
      that an increased purine nucleotide degradation and a decreased antioxidant
      defense may be responsible for the observed changes.

PMID- 8143240
TI  - Characterization of endothelin receptors mediating contraction and relaxation in
      rabbit saphenous artery and vein.
AB  - The endothelin receptors in rabbit isolated rings of saphenous artery and
      saphenous vein have been characterized using endothelin-1, endothelin-2,
      endothelin-3, sarafotoxin S6c, and BQ123. Although artery rings were more
      sensitive than those from vein to the contractile action of phenylephrine,
      endothelin-1 was about three times more potent as a contractile agonist on vein
      than on artery. In rings precontracted with phenylephrine, carbachol was 10 times
      more potent in vein than in artery rings to induce endothelium-dependent
      relaxation. However, in rings precontracted to a similar tone by endothelin-1,
      the relaxation elicited by carbachol was reduced in the vein but remained
      unchanged in the artery. In endothelium-denuded saphenous artery, endothelin-1
      and endothelin-2 elicited contraction with equal potency, whereas endothelin-3
      and sarafotoxin S6c were weak agonists. In saphenous vein, the rank order of
      sensitivity was sarafotoxin S6c > endothelin-2 > or = endothelin-1 = endothelin
      3, whereas sarafotoxin S6c and, to a lesser extent, endothelin-3 act as partial
      agonists. The ETA receptor antagonist BQ123 shifted, to the right, the
      concentration-response curves of endothelin-1 on endothelium-denuded saphenous
      artery (pA2 = 7.25). In the endothelium-denuded saphenous vein, 10 microM BQ123
      shifted to the right only the response to high concentrations of endothelin-1. In
      vein but not in artery, endothelin-1 and sarafotoxin S6c induced an endothelium
      dependent relaxation, which was increased, in the case of endothelin-1, in the
      presence of BQ123.2+.

PMID- 8143241
TI  - Sexual differences in hypothalamic adenosine 3',5'-cyclic monophosphate content.
AB  - Hypothalamic adenosine 3',5'-cyclic monophosphate (cAMP) concentration was
      measured in the morning (10:00) and afternoon (16:00) in castrated and intact
      rats of both sexes to evaluate a possible sexual difference. Castration produced
      different effects on the hypothalamic cAMP concentration. In females, ovariectomy
      significantly reduced total hypothalamic cAMP concentration, whereas in males,
      orchidectomy elevated hypothalamic cAMP content. This observation was independent
      of the time of day at which the animals were killed. On the other hand,
      administration of the alpha-adrenoreceptor blocking agent phenoxybenzamine or the
      beta-adrenoreceptor blocker propranolol lowered the concentration of cAMP in the
      hypothalamus. However, this effect was selective and related to the time of day
      when the animals were killed. Phenoxybenzamine reduced the hypothalamic cAMP
      content in males killed in the afternoon, whereas the effect of propranolol was
      significant in males killed in the morning. These results indicate a response of
      hypothalamic cAMP to adrenoreceptor blockers in male rats opposite to that
      reported previously from our laboratory in female rats, suggesting that the
      functional behavior of the hypothalamic adrenergic response is strongly sex
      related.

PMID- 8143242
TI  - Role of gastric acid secretion and blood flow in the development of vagal
      stimulation induced gastric mucosal damage.
AB  - Vagal stimulation has been shown to result in the development of gastric mucosal
      erosions in the rat, although the mechanisms underlying the development of such
      erosions are not known. The effects of vagal stimulation on gastric acid
      secretion and mucosal blood flow were examined in urethane-anesthetized male
      Sprague-Dawley rats to determine whether changes in these factors correlate with
      the mucosal damage in response to vagal stimulation. Electrical stimulation (5
      Hz, 5 V, 1 ms for 60 min) of afferent or efferent components of the vagi was not
      found to induce any significant increase in the mean acid secretory rate compared
      with control animals (p > 0.05). In contrast, stimulation of intact vagus nerves
      induced a significant increase in the mean acid secretory rate compared with
      control and efferent- and afferent-stimulated groups (p < 0.01). Measurement of
      gastric blood flow with laser-Doppler flowmetry demonstrated intact vagal
      stimulation to have no significant effect on gastric blood flow. These data
      suggest that such vagal stimulation induced increases in acid secretion in
      urethane-anesthetized animals may represent a part of the integrated
      physiological response to such stimulation which leads to the development of
      gastric mucosal erosions within 60 min. Pretreatment with antisecretory agents
      such as cimetidine and interleukin-1 beta significantly reduce the gastric
      mucosal injury compared with untreated animals (p < 0.05), emphasizing the
      important role of acid secretion in the development of vagal-induced gastric
      damage.

PMID- 8143243
TI  - Phosphatidylcholine metabolism in hypoxic and phospholipase C exposed rat
      ventricular myocytes.
AB  - A phospholipase C specific for choline and ethanolamine acyl and plasmalogen
      glycerophospholipids (PC-PLC) has been described in myocardial tissue. In the
      present study we investigated whether an endogenous PC-PLC is activated in
      hypoxic, substrate-free incubations of rat ventricular myocytes. The
      phosphatidylcholine pool of the myocytes was prelabelled with [14C]choline during
      a 4-h preincubation (pulse) period. The myocytes were subsequently washed and
      incubated for another 2 h (chase period) in normoxic, hypoxic, or hypoxic buffer
      supplemented with PC-PLC from Bacillus cereus. We hypothesized that an increase
      in the total (intracellular plus extracellular) content of [14C]phosphocholine
      (one of the products resulting from PC-PLC action on phosphatidylcholine)
      throughout the chase period would indicate PC-PLC activity. Instead, an apparent
      decrease was observed for this parameter in all myocyte groups (17-29%), even in
      the one exposed to exogenous PC-PLC. However, 60 min after the start of the chase
      period, the level of total [14C]phosphocholine was higher in hypoxic (p = 0.022)
      and hypoxic + PC-PLC exposed (p = 0.013) myocytes compared with normoxic
      controls. The total content of [14C]choline increased significantly (p < 0.017)
      in all myocyte groups during the incubation period (98-153%) as a result of an
      increment of this metabolite in the buffer. Furthermore, the values measured in
      hypoxic and hypoxic + PC-PLC exposed myocytes during the first hour of the chase
      period were significantly (p < 0.017) higher than the corresponding values in
      normoxic myocytes. The present results do not allow firm conclusions regarding
      endogenous PC-PLC activation in energy-depleted rat cardiac myocytes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143245
TI  - Predicting submaximal oxygen consumption during treadmill running in mice.
AB  - Treadmill exercise is the most common form of exercise used in studies involving
      laboratory rodents. However, oxygen consumption (VO2) is not usually monitored
      since the measurement of this parameter is particularly difficult in small,
      exercising animals. The purpose of this study was to develop a regression
      equation for predicting submaximal VO2 in mice during treadmill running. Twenty
      female mice of three strains were tested, in an Oxyscan metabolic treadmill, on
      different days at running speeds of 10, 13, 15, 17, and 20 m/min at a 0% grade.
      Each mouse was placed in the treadmill chamber for a 10-min period before running
      commenced. Running speed was increased in 2-min intervals by 5 m/min until the
      assigned speed was reached. Each mouse then ran for 10 min to reach steady state,
      followed by another 20 min at the steady-state plateau. During this period a 30-s
      expired gas sample was collected every minute. Gas samples were analyzed for O2
      and CO2, using an Oxyscan gas analyzer. Trials were conducted during the
      nocturnal phase of the animals' photoperiod, and running speeds were assigned
      randomly to minimize order effects. This approach provided highly reliable
      measures of oxygen consumption (r = 0.96). By using the running speeds (10-20
      m/min) and the animal's body weight it was possible to predict the submaximal
      oxygen consumption (mL/min) during running with a high degree of accuracy (i.e.,
      R2 = 0.85). In an independent group of animals (n = 14) we compared the predicted
      VO2 with the measured VO2. This yielded a good correlation coefficient (r = 0.79)
      and a low prediction error (+2.4 +/- 2.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143244
TI  - Effects of the enantiomers of a new dihydropyridine derivative, S12968 and
      S12967, on renal functions in rats.
AB  - The aim of this study was to evaluate the effects of the two enantiomers of a new
      dihydropyridine, S12967 and S12968, on rat renal function. Male Wistar rats were
      injected intravenously with saline, S12967, or S12968 (0.1, 0.3, or 1 mg/kg body
      weight). Urinary flow, glomerular filtration rate, renal plasma flow, urinary
      sodium, potassium, and calcium excretions, mean arterial pressure, and renal
      vascular resistance were determined before and every 30 min up to 180 min after
      administration of the tested substance. The levogyre enantiomer S12968, at a dose
      of 0.3 mg/kg, induced a 4-fold increase in urinary sodium excretion, without
      significant or with minor changes in glomerular filtration rate, renal plasma
      flow, or renal blood flow. The hypotensive effect was small and nonsignificant.
      At 1 mg/kg, S12968 caused a profound hypotensive effect that impaired the renal
      function, induced marked oliguria, and decreased glomerular filtration rate and
      renal blood flow to almost negligible values. The dextrogyre enantiomer S12967
      had much less effect on renal function. These data showing specific
      stereoselective renal effects are in agreement with pharmacological studies that
      have demonstrated that S12968 possesses a higher affinity for the dihydropyridine
      binding site than its dextrogyre enantiomer, S12967.

PMID- 8143246
TI  - Reduced noradrenaline responsiveness of brown adipocytes isolated from estradiol
      treated rats.
AB  - High plasma levels of estradiol are known to reduce the GDP binding of brown
      adipose tissue. Since GDP binding depends on the level of sympathetic discharge
      to brown adipose tissue, we measured the responsiveness to noradrenaline of brown
      adipocytes isolated from female rats with high plasma levels of estradiol.
      Noradrenaline responsiveness was assessed by measuring the respiration rate of
      isolated brown adipocytes in the presence of different concentrations of
      noradrenaline. Both control and treated adipocytes showed the same basal
      respiratory rate (27 +/- 6 and 24 +/- 4 nmol O2.min-1.10(-6) cells,
      respectively). The presence of noradrenaline (0.1, 1, and 10 microM) in the
      medium increased the respiration rate of both kinds of adipocytes in a dose
      dependent manner. However, the response was markedly reduced in adipocytes
      isolated from estradiol-treated rats. These results suggest that estradiol
      impairs the responsiveness of brown adipose tissue to the sympathetic nervous
      system. Three possible mechanisms are suggested as accounting for the observed
      decreased responsiveness to noradrenaline, i.e., a direct action of estradiol in
      brown adipocytes, a modulatory role of estradiol in the central control of the
      sympathetic discharge to brown adipose tissue, and the interference of
      catecholestrogens with noradrenaline synthesis at the sympathetic terminals.

PMID- 8143247
TI  - Evaluation of abomasal outflow diversion as an experimental model of
      hypochloremic, hypokalemic metabolic alkalosis in lactating cows.
AB  - Four adult, lactating dairy cows were subjected to diversion (loss) of gastric
      contents through a T-shaped cannula placed in the cranial part of the duodenum
      just distal to the pylorus. Diversion was continued for 10 to 12 hours, at which
      point the cows were very weak and depressed. The volume of effluent during this
      period ranged from 37.3 to 46.8 L, with the largest volume being produced during
      the first four hours. All cows became dehydrated, with mean packed cell volume
      and total plasma protein concentration increasing 30% and 19.6%, respectively,
      but with only a slight increase in plasma creatinine concentration. Plasma Cl-
      concentrations decreased from a mean of 97.3 mEq/L at the beginning of diversion
      to a mean of 87.2 mEq/L at eight hours. This was followed by a plateau or slight
      increase in concentrations over the final hours of diversion. Plasma K+
      concentration followed a similar pattern, decreasing from a mean of 3.9 mEq/L to
      a mean of 2.94 mEq/L at six hours, followed by increasing values until
      termination of diversion. No changes in plasma Na+ concentration were noted,
      except for a mild decrease in one cow. Plasma calcium concentrations decreased
      significantly, reaching 6.6 +/- 0.6 mEq/L at the end of diversion. Venous pH,
      plasma HCO3- concentration, and plasma base excess concentration increased during
      the first four to eight hours of diversion, followed by a gradual decline.
      Although a mild hypochloremic metabolic alkalosis resulted from diversion of
      abomasal outflow in all cows, substantiated by a mild increase in plasma strong
      ion difference, the changes observed were not as great as expected.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143248
TI  - Immunohistochemical evidence for immunoglobulin and complement deposition in
      spinal cord lesions in degenerative myelopathy in German shepherd dogs.
AB  - The purpose of this study was to examine the distribution of immunoglobulin and
      complement component C3 in spinal cord tissues of dogs with degenerative
      myelopathy. Sections of formalin-fixed paraffin-embedded spinal cord from five
      German Shepherd dogs with clinical and histological features consistent with
      degenerative myelopathy (DM) and one normal dog were tested immunohistochemically
      for deposition of immunoglobulin G (IgG) and the third component of complement
      (C3). In all dogs there was staining associated with large and small blood
      vessels. In addition, in the dogs with DM there was focal staining for IgG and C3
      in spinal nerve tracts characteristically affected in DM. Deposition of IgG and
      C3 was found in histological lesions, and in addition, in other areas independent
      of visible lesions, suggesting that IgG and C3 deposition may precede
      histological evidence of spinal cord damage. These findings suggest a role for
      immune-mediated destruction of the spinal cord which may contribute to the
      pathogenesis of DM in German Shepherd dogs.

PMID- 8143249
TI  - Experimental model of swine pneumonic pasteurellosis using crude Actinobacillus
      pleuropneumoniae cytotoxin and Pasteurella multocida given endobronchially.
AB  - This study was designed to develop and characterize a swine pneumonic
      pasteurellosis model by concurrent introduction of Pasteurella multocida type A
      and Actinobacillus pleuropneumoniae crude cytotoxin. After a series of
      preliminary experiments, a combination of 4 x 10(9) P. multocida and 4,000 toxic
      units of A. pleuropneumoniae crude cytotoxin was determined to produce optimal
      results. A total of 48 pigs were divided into four groups of 12 pigs each. The
      control group received buffered saline only. Four pigs from each group were
      randomly selected for necropsy 3, 7 and 14 days postinoculation (PI). Inoculation
      of pigs with P. multocida and A. pleuropneumoniae cytotoxin (group 1) resulted in
      moderate to severe pneumonia. Pasteurella multocida was isolated from pneumonic
      lesions, grossly normal lung, and bronchial lymph nodes of all group 1 pigs
      throughout the 14 day experimental period. Pathological changes typical of field
      cases of swine pneumonic pasteurellosis were produced. Pigs inoculated with P.
      multocida alone (group 2) had pneumonic lesions and P. multocida was reisolated
      from lungs at three days PI. Pasteurella multocida was not isolated from these
      pigs at 7 and 14 days PI, except for one pig in which an abscess developed in the
      thorax. Pulmonary lesions induced by A. pleuropneumoniae crude cytotoxin alone
      (group 3) were transient and resolved by seven days PI. Group 1 pigs had
      significantly greater lung lesion volumes than group 2 and 3 pigs at 3, 7 and 14
      days PI. Statistical analysis indicated a significant interactive effect of P.
      multocida and A. pleuropneumoniae cytotoxin on the development of lung lesion
      volumes at 7 and 14 days PI (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143250
TI  - Passive immunity to Pasteurella haemolytica A1 in dairy calves: effects of
      preparturient vaccination of the dams.
AB  - Dairy cows from five herds were assigned to receive a commercial Pasteurella
      haemolytica vaccine or no vaccine at all, administered at six and three weeks
      before parturition. Vaccination was associated with increased leukotoxin
      neutralizing serum antibody titers in the dams (p < 0.001), and with increased
      titers in colostrum (p < 0.001). Vaccination of dams also had a significant
      association with increased passive leukotoxin neutralizing antibody titers in
      their calves (p < 0.001). Vaccination was also associated with increased indirect
      agglutinating antibody titers in serum of the dams (p < 0.001). In the analysis
      of agglutinating antibody titers in colostral whey the interaction
      "vaccination*herd" was found to be significant (p < 0.001), indicating that the
      effects of vaccination on colostral titers were not consistent from herd to herd.
      The analysis was repeated, stratifying by herd. Vaccination was associated with
      increased agglutinating antibody titers in colostrum (p < 0.05) in three herds of
      the five in the study. In two of these three herds there were significant
      increases in passive neonatal titers associated with vaccination. In the
      remaining herd the mean IgG1 level in the calves was consistent with failure of
      passive transfer of immunoglobulins (IgG1 < 8.0 g/L). These results suggest that
      preparturient vaccination of dairy cows can induce modest increases in passive
      antibody titers to antigens of Pasteurella haemolytica in their calves, but the
      antigen of interest and the population being studied can affect the outcome.

PMID- 8143251
TI  - A serological survey for bovine immunodeficiency-like virus in Ontario dairy
      cattle and associations between test results, production records and management
      practices.
AB  - A chemiluminescence Western blot analysis (WBA) for detecting antibovine
      immunodeficiency-like virus (BIV) antibodies, had good repeatability. The test
      was subsequently applied to a bank of serum samples from 928 adult cows from 265
      herds in Ontario; the number of cows sampled within each herd ranged from 1 to
      13. The overall prevalence of anti-BIV antibodies among cows was 5.5% with a 95%
      confidence interval of 4.2% to 7.2%. In contrast, 18.1% of herds had at least one
      reactor among cows tested, resulting in a herd-prevalence confidence interval of
      13.8% to 23.4%. These estimates of prevalence were in the same range as previous
      reports from the US and Europe. Bovine immunodeficiency-like virus may have a
      worldwide distribution. Unfortunately, BIV test sensitivity and specificity are
      difficult to estimate because virus isolation is inefficient. Therefore, the
      apparent prevalences could not be adjusted for test sensitivity and specificity,
      to estimate the true prevalence of infection. The serum samples had previously
      been tested for antibodies to bovine leukemia virus (BLV). There were no
      significant associations between BIV and BLV test results. Least squares
      regression was used to investigate potential associations between BIV test
      results and selected production indices.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143252
TI  - Interaction of bovine respiratory syncytial virus with bovine alveolar
      macrophages in vivo: effects of virus infection upon selected cell functions.
AB  - The effect of bovine respiratory syncytial virus (BRSV) upon alveolar macrophage
      (AM) function was investigated using an in vivo calf inoculation model. Alveolar
      macrophages were collected sequentially from live calves at multiple time points
      during the 14 day period following viral inoculation. Alveolar macrophages from
      bronchoalveolar lavage fluids were purified by density gradient centrifugation (>
      95% AM) prior to in vitro evaluation of cell functions. There were significant
      but variable and inconsistent differences in the functions of AM from the BRSV
      inoculated calves compared to the control calves. Fc-receptor mediated
      phagocytosis was either increased or unchanged by BRSV inoculation. Nonopsonized
      phagocytosis was decreased during the early postinoculation period and later
      increased. There was a variable effect on AM phagosome lysosome fusion with
      increased fusion activity on postinoculation days 2 through 5, 7 and 12 but
      reduced activity on days 6 and 10. The AM respiratory burst, as measured by
      nitroblue tetrazolium dye reduction, was essentially unaffected with a reduction
      in activity on day 10 only. In this model, BRSV inoculation of calves primarily
      resulted in an alteration of the membrane associated phagocytic functions of the
      alveolar macrophages (p < 0.05).

PMID- 8143253
TI  - Evaluation of the antibody response in pigs vaccinated against Streptococcus suis
      capsular type 2 using a double-antibody sandwich enzyme-linked immunosorbent
      assay.
AB  - A double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was
      standardized for the detection of specific antibodies following vaccination with
      Streptococcus suis capsular type 2 bacterins. No statistically significant
      increase of antibody titers was detected in vaccinated piglets compared to the
      nonvaccinated control group, even if a minority of piglets demonstrated an
      important postvaccinal response. Three of four vaccinated sows showed a low
      antibody response to vaccine and specific immunity was detected in piglets of
      only one litter of these three sows. Passive protection studies showed that none
      of the sera from vaccinated piglets were protective for mice whereas serum
      obtained from hyperimmunized pigs gave protection.

PMID- 8143254
TI  - Porcine reproductive and respiratory syndrome virus: morphological, biochemical
      and serological characteristics of Quebec isolates associated with acute and
      chronic outbreaks of porcine reproductive and respiratory syndrome.
AB  - Cytolytic and noncytolytic strains of the porcine reproductive and respiratory
      syndrome virus (PRRSV) were isolated in primary cultures of porcine alveolar
      macrophages (PAM) from lung homogenates of stillborn fetuses or blood samples of
      dyspneic piglets collected from Quebec pig farms having experienced acute or
      chronic outbreaks of PRRS. Serological identification of the virus was confirmed
      by indirect immunofluorescence and indirect protein A-gold immunoelectron
      microscopy using reference antiserum prepared from experimentally-infected
      specific pathogen free (SPF) piglets and monoclonal antibodies (MoAbs) directed
      against the p15 nucleocapsid (N) protein of the reference ATCC-VR2332 isolate.
      Intracytoplasmic enveloped viral particles that tended to accumulate into
      cytoplasmic vesicles were observed in the infected PAM; no budding was
      demonstrated at the level of the cytoplasmic membrane. The extracellular virions
      appeared as pleomorphic but mostly spherical enveloped particles, 50-72 nm in
      diameter (averaged diameter of 50 particles was 58.3 nm), with an isometric core
      about 25-30 nm. Buoyant density of the virus in CsCL density gradients was
      estimated to 1.18-1.20 g/mL. No hemagglutinating activity was demonstrated.
      Analysis of semipurified virions of isolate IAF-exp91 by radioimmunoprecipitation
      (RIPA) and Western immunoblotting experiments, using reference rabbit and porcine
      hyperimmune sera, revealed four major viral proteins, a predominant 15 kD N
      protein and three other proteins with predicted M(r_ of 19, 26 and 42 kD. Progeny
      viral particles produced in PRRSV-infected PAM in the presence of tunicamycin
      lacked the 42 kD protein, thus confirming its N-glycosylated nature.
      Immunoprecipitation experiments using the anti-ATCC-VR2332 MoAbs confirmed the
      close antigenic relationships between Quebec and American reference isolates of
      PRRSV.

PMID- 8143255
TI  - Echocardiographic evidence for myocardial failure induced by taurine deficiency
      in domestic cats.
AB  - Dietary taurine-deficiency is a cause of dilated cardiomyopathy (DCM) in cats.
      While the incidence of clinical cases of feline DCM has markedly decreased since
      the association between DCM and taurine-deficiency was first recognized, not all
      cats maintained on taurine-deficient diets develop DCM. The objective was to
      temporally evaluate left ventricular (LV) function using M-mode echocardiography
      in 23 cats maintained on a taurine-deficient diet; 20 time-matched, taurine
      supplemented cats served as controls. The duration of feeding trials ranged from
      6-15 months. No diminution of myocardial function was recorded in a small number
      of taurine-deficient cats whereas cardiac performance in some taurine-deficient
      cats diminished to levels characteristic of DCM. Of the taurine-deficient cats,
      17 (74%) experienced a greater than 25% reduction in fractional shortening and 21
      (91%) had a greater than 25% increase in LV end-systolic short-axis diameter. On
      average, LV end-systolic short-axis diameter increased by 70% and fractional
      shortening decreased by 37% in taurine-deficient cats. Mean velocity of
      circumferential fiber shortening was similarly reduced in taurine-deficient cats.
      The greatest rate of change in M-mode echocardiographic variables occurred during
      the first four months on the taurine-deficient diet. Dietary taurine deficiency
      leads to a spectrum of changes in myocardial function in domestic cats. While DCM
      is observed in some cats, decreased systolic pump function and increased LV end
      systolic short-axis diameter are more consistent findings.

PMID- 8143256
TI  - Restriction endonuclease analysis of a porcine isolate of bovine herpesvirus type
      1.
AB  - Deoxyribonucleic acid (DNA) was extracted from bovine herpesvirus type 1 (BHV-1)
      isolated from a stillborn porcine fetus, from the Cooper reference strain of BHV
      1, and from an Ontario bovine respiratory isolate. Each DNA was digested with the
      restriction endonucleases HindIII, EcoRI, HpaI and BamHI. Except for very minor
      differences in the patterns produced after digestion with EcoRI and HindIII, the
      DNA of the porcine isolate reacted in a similar manner to the bovine viruses, and
      it was concluded that the porcine virus is genetically similar to bovine isolates
      of BHV-1.

PMID- 8143257
TI  - Effect of repeated administration of tirilazad mesylate on healthy and
      endotoxemic calves: a pilot study.
AB  - Tirilazad mesylate (TM:U74006F), a nonglucocorticoid 21-aminosteroid (lazaroid),
      is beneficial in the treatment of experimentally-induced ischemic injury
      following brain and spinal cord trauma, subarachnoid hemorrhage, hypovolemic
      shock and endotoxemia. This study investigated the effects of TM following
      repeated administration in sixteen healthy and endotoxemic calves. Group A calves
      received TM 3 mg/kg IV; group B calves received Escherichia coli endotoxin in
      increasing doses (0.1 to 20 micrograms/kg IV); group C calves received TM and
      endotoxin and group D calves received sterile saline (10 mL). Endotoxin, TM and
      saline were given every eight hours for five days. Mild, transient tachypnea was
      observed following TM administration. The drug suppressed clinical signs of
      endotoxemia until larger doses of endotoxin were given. At necropsy no
      substantial lesions were observed in groups A and D. Groups B and C had lesions
      consistent with endotoxemia but only group C calves had evidence of abomasal and
      ruminal ulceration. Although TM may be of benefit in the treatment of
      endotoxemia, further studies are needed to determine the optimal dosage and
      potential side effects in the endotoxic bovine neonate.

PMID- 8143258
TI  - Monoclonal antibodies to bovine viral diarrhea virus: cross-reactivities to field
      isolates and hog cholera virus strains.
AB  - Monoclonal antibodies to bovine viral diarrhea virus (BVDV) were examined for
      binding with a large number of North American BVDV isolates and eight strains of
      the serologically related pestivirus, hog cholera virus (HCV). No single BVDV
      monoclonal antibody reacted with all BVDV isolates. The most cross-reactive
      monoclonal antibody was an anti-p80/p125 antibody which showed a positive
      reaction with 173 of 180 (96%) North American isolates. From a fewer number of
      isolates tested, one anti-gp53 monoclonal antibody also showed a high cross
      reactivity (94%). All BVDV isolates showed a positive reaction with at least one
      of the seven monoclonal antibodies in the panel. Thus, the results indicated that
      a pool of these monoclonal antibodies may be used in place of polyclonal antisera
      for the detection of BVDV contamination of cell lines or for virus isolation. For
      HCV, all three anti-p80/p125 monoclonal antibodies reacted positively with all
      eight virus strains. In contrast, none of the anti-gp53 monoclonal antibodies
      were reactive to HCV strains. Thus, the anti-gp53 monoclonal antibodies may be
      useful for distinguishing between usually innocuous BVDV infections and the
      highly significant HCV infections in swine for foreign animal disease
      surveillance.

PMID- 8143259
TI  - Chymotrypsin and trypsin sensitivities of avian reoviruses.
AB  - Experiments were undertaken to examine the chymotrypsin sensitivity and trypsin
      sensitivity of 13 avian reoviruses, and to determine if there was any correlation
      with pathogenicity of some chicken reoviruses. A wide variation in the degree of
      sensitivity of avian reoviruses to chymotrypsin and trypsin was observed.
      Overall, the infectivity of the 13 avian reoviruses for Vero cells was markedly
      reduced by treatment with 0.01% chymotrypsin (the lowest concentration tested)
      while 0.5% trypsin significantly reduced the infectivity of 9 of 13 strains.
      Comparison of four avian reoviruses, three resistant and one sensitive to
      trypsin, for pathogenicity in day old chicks following oral inoculation showed
      the strains that were resistant to trypsin to be more pathogenic. Tenosynovitis
      and virus persistence in intestines, liver, heart and hock joint tissues occurred
      only in chickens inoculated with the trypsin resistant strains. It is concluded
      that the degree of sensitivity to chymotrypsin and trypsin among avian reoviruses
      is heterogenous. Sensitivity to trypsin influenced the development of
      tenosynovitis based on microscopic lesions and virus persistence in tissues.

PMID- 8143260
TI  - Clinical features of atopic dermatitis.

PMID- 8143261
TI  - The immunologic basis of atopic dermatitis.

PMID- 8143262
TI  - The role of allergens in atopic dermatitis.
AB  - AD is a disorder that affects up to 12% of the pediatric population. This disease
      is multifactorial and encompasses a wide array of etiologic factors. Strong
      evidence has existed in the literature over the past century for the role of
      inhalant and food allergies in the pathogenesis of AD. Much work is currently
      ongoing to delineate the role of individual cellular components, cytokines, and
      other mediators in the pathogenesis of AD. The answers to these questions, as
      well as a more comprehensive understanding of hereditary factors, will provide
      key information to our overall understanding of AD and our ability to treat
      patients with this disease more effectively in the future.

PMID- 8143263
TI  - The role of microorganisms in atopic dermatitis.

PMID- 8143264
TI  - Immunopharmacologic aspects of atopic dermatitis.

PMID- 8143265
TI  - New therapeutic approaches in atopic dermatitis.
AB  - Novel approaches to the therapy for atopic dermatitis (AD) can now be considered
      because of recent advances in the pathogenesis of the disease. Several of these
      concepts are being tested in clinical trials. The effectiveness of cyclosporin A,
      plus reports of adoptive transfer of AD, or its clearing, following bone marrow
      transplantation, verify the criticalness of immune cells in AD pathogenesis.
      Thus, there is renewed interest in immunosuppressives, such as azathioprine and
      methotrexate, as well as new adhesion molecule and T-cell activation inhibitors.
      Therapy with the T-cell lymphokine, interferon-gamma, or the thymic hormone,
      thymopentin, is designed to inhibit the IL-4-dominated response of AD T-cells.
      This approach, rather than directly suppressing all immune responsiveness,
      represents a more specific targeting to improve the balance of a chronically
      disordered immune response. Recent findings of a therapeutic advantage of longer
      wavelength phototherapy over UVB therapy may relate to specific immunologic
      events following UVB vs UVA photoinjury that are critical to the exacerbation of
      AD. Complex herbal mixtures used in traditional Chinese medicine are currently
      being evaluated, but toxicity and palatability may be limiting. Other dietary
      approaches, such as modifying the lipid balance, have generally not had much
      benefit. Because the safety and efficacy of the above treatments need further
      exploration, the physician must continue to utilize fundamental methods, such as
      mitigating trigger factors (i.e., microbes and stress, and certain foods in
      persons with documented sensitivity), on improving the abnormal epidermal lipid
      barrier to irritation, and on reducing cutaneous inflammation with mild topical
      steroids.

PMID- 8143266
TI  - Tetrasomy 8 as a clonal anomaly in myeloid neoplasias.
AB  - Tetrasomy of chromosome 8 as a sole anomaly is apparently extremely rare in acute
      non-lymphocytic leukemia (ANLL): Only two cases have been reported, one of ANLL
      (M5b) with this karyotype. Very recently, another case was reported of a
      myelodysplastic syndrome (MDS) with isolated tetrasomy 8. We report tetrasomy 8
      in four cases of ANLL, two of them with M5 and one with M1 subtype. Although in
      the latter case, tetrasomy 8 was evident in all karyotypes analyzed, in all other
      cases it constituted a subpopulation of cells other than those with trisomy 8 and
      those with a normal karyotype (in only one case another change was evident in the
      karyotype). Using fluorescence in situ hybridization (FISH), the proportion of
      tetrasomic cells was determined in interphase nuclei. By this technique, small
      cell populations (3-9%) were detected in three additional trisomy cases. An
      additional "control" group of five trisomy cases did not show a significant
      population of tetrasomic interphase nuclei. The data show that tetrasomy 8, if
      present as a sole anomaly in ANLL, may play a rather specific role for the
      subtype, and probably for the progression of myeloid neoplasia as well.

PMID- 8143267
TI  - Translocation (12;22)(p13;q12) as sole karyotypic abnormality in a patient with
      nonlymphocytic leukemia.
AB  - Cytogenetic analysis of unstimulated bone marrow (BM) and peripheral blood (PB)
      cells of a patient with clinical features of atypical chronic myeloid leukemia
      (CML) showed t(12;22)(p13;q12) as the sole karyotypic abnormality. Subsequent
      fluorescence in situ hybridization (FISH) with abl- and bcr-specific cosmids as
      well as chromosome 12- and 22-specific DNA libraries and Southern blot analysis
      confirmed that in this patient t(12;22) does not constitute a cryptic Ph variant.
      Recently, a few very similar cases were reported by other investigations. The
      possible significance of this translocation as a new cytogenetic marker for
      nonlymphocytic leukemia is discussed.

PMID- 8143268
TI  - Cytogenetic findings in primary uveal melanoma.
AB  - We analyzed cytogenetic abnormalities in 10 cases of primary uveal melanoma.
      Clonal chromosomal abnormalities were present in nine cases. Chromosome 6 was
      most commonly affected (seven cases) and included gain of material from 6 and/or
      loss of material from 6q. Trisomy of chromosome 8 or gain in material from 8q,
      mostly in the form of an i(8q) resulting in three to five copies of the 8q
      segment was seen in six cases. Monosomy of chromosome 3 and rearrangements of
      chromosome 9 were less frequent and were altered in three cases each. Clinical,
      histopathologic, and cytogenetic abnormalities are correlated.

PMID- 8143269
TI  - Karyotypic analysis of a heterogeneous human transitional cell carcinoma of the
      bladder.
AB  - The UCRU-BL-17 (BL-17) series of xenografts, tissue culture sublines, and cloned
      cell lines (Fig. 1) shows a range of heterogeneous growth characteristics both in
      vitro and in vivo (Table 1) and represents a model of human bladder cancer
      heterogeneity. Cytogenetic analysis was undertaken to determine if specific
      chromosome changes correlated with particular aspects of the heterogeneous
      phenotypes. The BL-17 sublines and cloned cell lines shared many common
      chromosome abnormalities. Indeed, the cloned cell lines showed nearly identical
      karyotypes despite their marked differences in growth characteristics. Karyotypic
      evolution with passage through the nude mice was apparent, however. This
      evolution occurred at the specific chromosome regions of 1p12, 3cen-3p21, and
      6cen-6q21. Whether the heterogeneity of karyotype between the BL-17 cell lines
      resulted from the existence of multiple clones in the original patient tumor or
      from karyotypic instability through passage in nude mice is uncertain, but in
      either case the specificity of karyotypic evolution observed suggests that 1p12,
      3cen-3p21, and 6cen-6q21 are hotspots for rearrangement in the BL-17 tumor. No
      specific correlations between chromosome abnormalities and biologic
      characteristics could be made, but several unique karyotypic features arose in
      the progression to two of the sublines, BL-17/23 alpha and BL-17/0/X2A,
      coinciding with a loss of anchorage-independent growth by BL-17/23 alpha and a
      change in growth in vivo from a solid tumor to a fluid-filled tumor by BL
      17/0/X2A.

PMID- 8143270
TI  - Cytogenetic analysis of a leiomyosarcoma of the kidney.
AB  - Nonepithelial malignant renal tumors are very rare, comprising approximately 2-3%
      of all malignant renal tumors. We were able to culture and subsequently karyotype
      a leiomyosarcoma (LMS) of the kidney that showed the following representative
      karyotype: 84,XY,add(X)(q25),-Y,add(1)(p11),dic(1;20) (p34;q13.3),-5,
      6,dup(6)(q24),i(7)(p10),add(8)(p11),-9,-11,add(13)(p11), -15,-15 ,
      add(17)(q24)x2,-18,-19,-21,-22,-22, +mar1(?hsr),+mar2,+2mar. A clonal add(1)(q11)
      was also evident. The DNA index was 1.9. Our results as compared with data from
      the literature suggest that LMS of the kidney has most cytogenetic aberrations
      reported to be characteristic of LMS, especially those located in the abdomen,
      and that different genetic mechanisms of initiation and progression appear to
      play a role in LMS of similar histology but from different anatomic sites.

PMID- 8143271
TI  - Analysis of oncogene expression in primary human gliomas: evidence for increased
      expression of the ros oncogene.
AB  - Expression of a panel of oncogenes and potential oncogenes was studied in normal
      human brain and in 17 human gliomas, including three low- and 14 high-malignancy
      grade tumors. PolyA RNA was isolated from glioma biopsies and used as template
      for reverse transcriptase-catalyzed synthesis of radioactively labeled cDNA.
      Labeled cDNA was then hybridized to filters to which probes for various oncogenes
      had been attached. Increased signal intensity, as compared with that of normal
      brain, was observed for the ros oncogene in six of 17 gliomas, including gliomas
      of both low and high malignancy grades. Increased ros expression was verified by
      Northern blot analysis in one tumor. These results suggest that increased ros
      expression may play a role in tumorigenesis in a significant proportion of
      gliomas. Increased expression of other genes, including the erbA2, mel, and ets
      oncogenes was observed in a smaller proportion of the gliomas tested, suggesting
      a possible role for these oncogenes in individual tumors but no generalized role
      in development or progression of human gliomas.

PMID- 8143272
TI  - Cytogenetic studies of four hemangiopericytomas.
AB  - We report cytogenetic studies on four hemangiopericytomas using in situ culture
      and robotic harvesting. Simple clonal chromosome abnormalities were observed in
      each of the three successful tumors. A cerebral tumor had a nonconstitutional
      46,XX,t(7;12)(p15;q15) karyotype. A recurrent cerebral tumor had two cell lines:
      one with a 46,XY,t(2;12)(p13;q24.1) karyotype and one with a
      46,XY,t(5;7)(q13;p15) karyotype. Each of the metaphases from a lung tumor had a
      46,Y,inv(X)(p22.3q13) karyotype. We conclude that simple nonconstitutional
      balanced chromosome anomalies of 7p15 and 12q are common in cerebral
      hemangiopericytomas. It is possible that balanced anomalies of these chromosome
      regions are related to the pathogenesis of this tumor type.

PMID- 8143273
TI  - Aberrations of chromosome 22 and polysomy of chromosome 8 as non-random changes
      in clear cell sarcoma.
AB  - Cytogenetic analysis was performed on a primary tumor and a metastatic lesion of
      a clear cell sarcoma of tendons and aponeuroses (CCS), a rare soft tissue
      neoplasm of uncertain histopathologic origin. Clonal chromosomal abnormalities
      resulting in two related clones were found in both tumors. The karyotype was near
      triploid with several structural and numerical changes, comprising a der(15;22)
      (q10;q10). Including the present case, 14 of 15 cases of CCS have had structural
      or numerical aberrations of chromosome 22 and nine of them (65%) displayed a
      similar or identical t(12;22)(q13-14;q12-13). Our findings suggest that in the
      absence of specific t(12;22), other abnormalities of chromosome 22 may be
      significant. In addition, increased doses of chromosome 8 found in 70% of the
      tumors strongly suggest a significant role for this chromosome in the development
      of clear cell sarcoma.

PMID- 8143274
TI  - Chromosome abnormalities in adenolipomas of the breast: karyotypic evidence that
      the mesenchymal component constitutes the neoplastic parenchyma.
AB  - Cytogenetic analysis of adenolipomas of the breast, a tumor type that has not
      been chromosomally characterized before, revealed the karyotypes 47,XX,
      +del(1)(p22) in one tumor and 46,XX, t(12;16)(q15;q24) in the other. Breast
      adenolipomas thus seem to be karyotypically identical to sporadic lipomas in
      other locations: rearrangements of 12q13-15 are the most common cytogenetic
      aberrations in lipomas, and also breaks in and around 1p22 have been reported in
      such tumors. The similarity with lipoma could be documented further in case 2, in
      which epithelial and mesenchymal cells were cultured separately; the t(12;16) was
      present in the latter but not in the former. This is evidence that the connective
      tissue is the neoplastic parenchyma in adenolipomas of the breast, whereas the
      glandular elements show concomitant but nonneoplastic proliferation.

PMID- 8143275
TI  - A new cytogenetic finding in an epithelioid sarcoma, t(8;22)(q22;q11).
AB  - We report a new translocation t(8;22)(q22;q11) in a single case of epithelioid
      sarcoma. The band involved in chromosome 22 is the same found in 70-80% of the
      case of Ewing's sarcoma/peripheral neuroepithelioma (PNET) with cytogenetic
      characterization. The histologic characteristics of this tumor were typical for
      epithelioid sarcoma. Immunohistochemical stains were also entirely consistent
      with this diagnosis, including non-reactivity with P30/32MIC2, a specific marker
      for Ewing's sarcoma/primitive neuroepithelioma.

PMID- 8143277
TI  - Double minute chromosomes in an invasive adenocarcinoma of the prostate.
AB  - Cytogenetic analysis of an uncultured, primary and invasive adenocarcinoma of the
      prostate showed several clonal abnormalities in a hyperdiploid karyotype,
      including double minute (dmin) chromosomes. The latter, although sporadic in this
      type of tumor, were previously reported in two cases of invasive prostatic
      cancer. This anomaly may therefore be associated with increased malignant
      properties.

PMID- 8143276
TI  - No rearrangements of the CHOP gene in malignant fibrous histiocytoma.
AB  - The human transcription factor gene, CHOP, which maps to 12q13, was recently
      shown to be disrupted by the t(12;16)(q13;p11) in myxoid liposarcoma. The most
      common soft tissue sarcoma, malignant fibrous histiocytoma (MFH)
      histopathologically may contain liposarcoma like areas and is often characterized
      by complex chromosome anomalies, which may include 12q13-15 aberrations, but
      never as t(12;16). By Southern blot technique, we detected no rearrangements of
      the CHOP gene in 41 MFH, including five with liposarcoma like areas. Thus,
      rearrangements of the CHOP gene appear to be specific for myxoid liposarcoma with
      t(12;16) and are not associated with lipoblastic differentiation.

PMID- 8143278
TI  - Nonrandom sex chromosome changes in brain tumors.

PMID- 8143279
TI  - An improved procedure for chromosome preparations from solid tumors.

PMID- 8143280
TI  - Trisomy 12 in chronic lymphocytic leukemia. An interphase cytogenetic study by
      fluorescence in situ hybridization.
AB  - B-cell chronic lymphocytic leukemia (CLL) is a rare disorder in the Chinese
      population. We evaluated the use of fluorescence in situ hybridization (FISH)
      with a chromosome 12-specific probe in the detection of trisomy 12 in interphase
      cell of 19 Chinese CLL patients. FISH successfully detected trisomy 12 in two
      cases, one of which had normal conventional cytogenetic findings, giving an
      incidence of 10%. The low incidence of trisomy 12 in our CLL patients may also
      reflect a biologic difference of this rare disorder in our population, compared
      to that of the West.

PMID- 8143281
TI  - Cytogenetic triclonality in acute myeloid leukemia: a morphologic, immunologic
      and in situ hybridization study.
AB  - Cytogenetically unrelated clones are uncommon in hematologic malignancies. We
      report a case of acute myeloid leukemia, which consisted morphologically of two
      populations of small and large blasts demonstrating immunophenotypic
      heterogeneity. Cytogenetic analysis showed 3 karyotypically abnormal clones:
      47,XY, +14/45,XY,dic(5;17)(q11;p11),14dmin, and a near-tetraploid clone. In situ
      hybridization showed that the near-tetraploid clone corresponded to the large
      blasts, and the near-diploid clones the small blasts, therefore demonstrating a
      direct relationship between cell size and DNA content. The diverse morphologic,
      immunologic and cytogenetic heterogeneity observed in our case suggested
      hematopoietic oligoclonality.

PMID- 8143282
TI  - Inversion (14)(q11q32) in childhood T-cell acute lymphoblastic leukemia.
AB  - Inversion (14)(q11q32) is a common cytogenetic aberration in T-cell chronic
      lymphoid malignancies but is rare in T-cell acute lymphoblastic leukemia (T-ALL).
      We describe two cases of childhood T-ALL in which inv(14)(q11q32) was present
      concomitantly with other karyotypic aberrations typical of T-ALL. The possible
      significance of inv(14) in these cases is also discussed.

PMID- 8143283
TI  - Granulomatous slack skin: cytogenetic and molecular analyses.
AB  - Granulomatous slack skin (GSS) is a rare disorder which is considered a slowly
      evolving T-cell lymphoma associated with granulomatous inflammation that mediates
      clastolysis. A combined cytogenetic, molecular, and cellular analysis was
      conducted on a clinically and histologically defined case of GSS. Cell cultures
      obtained from the skin biopsy showed trisomy of chromosome 8, and the DNA sample
      extracted from the skin biopsy showed a T-cell receptor beta-chain rearrangement.

PMID- 8143284
TI  - Mechanism of enzymic glycoside hydrolysis and of glycosyl transfer by
      glycosidases and glycosyltransferases.

PMID- 8143285
TI  - Synthesis and evaluation of diastereoisomeric alkylating pseudo-disaccharides as
      potential affinity reagents for trehalase.
AB  - Reaction of (+/-)-(3/4,5,6)-4-bromo-5,6-epoxy-3-hydroxycyclohexene with 2,3,4,6
      tetra-O-acetyl-1-thio-alpha-D-glucopyranose, followed by treatment of the
      resulting isolated diastereoisomeric 4-bromo-3,5-dihydroxycyclohexene 1
      thioglycoside derivatives with base under phase-transfer conditions, gave (R)-
      and (S)-(3,4,6/5)-3,4-epoxy-6-S-(1-thio-alpha-D-glucopyranosyl)-5-
      hydroxycyclohexene. None of them was substrate or inhibitor for cockchafer
      trehalase.

PMID- 8143286
TI  - Suicide-substrate inactivation of beta-galactosidase by diazomethyl beta-D
      galactopyranosyl ketone.
AB  - Diazomethyl beta-D-galactopyranosyl ketone (1) has been proven to be a mechanism
      based, irreversible (suicide-substrate) inactivator of Aspergillus oryzae beta-D
      galactosidase, but not an inactivator of E. coli lacZ beta-D-galactosidase.
      Compound 1 is stable in buffers of normal physiological pH. It is decomposed by
      H+, but not by nucleophiles. Inactivation of A. oryzae beta-D-galactopyranosyl
      ketone (2) nor diazomethyl alpha-D-galactopyranosyl ketone inactivated the enzyme
      and therefore inactivation is stereospecific, excess inhibitor could be separated
      from inactive enzyme without regain of activity and therefore it is bound
      irreversibly, and a second pulse of enzyme is inactivated at the same rate as
      enzyme inactivated to 95% activity by the first pulse. Diazomethyl beta-D
      glucopyranosyl ketone (2) inhibited sweet almond beta-D-glucosidase.

PMID- 8143287
TI  - Chemoenzymic synthesis of sialylated and fucosylated oligosaccharides having an N
      acetyllactosaminyl core.
AB  - Several sialylated and fucosylated oligosaccharides, based upon the N
      acetyllactosaminyl core structure, have been synthesized from a single
      trisaccharide glycoside, beta-D-GlcNAc-(1-->3)-beta-D-Gal-(1-->4)-beta-D-GlcNAc
      OCH2(CH2)++ +7CO2CH3, by the sequential use of several glycosyltransferases and
      one sialidase. In these chemoenzymic syntheses, selective internal
      monofucosylation of a dimeric N-acetyl-lactosaminyl tetrasaccharide is achieved
      via two routes. It is demonstrated that the pentasaccharide beta-D-Gal-(1-->4)
      beta-D-GlcNAc-(1-->3)-beta-D-Gal-(1-->4)-[alpha- L-Fuc-(1-->3)]-beta-D-GlcNAc
      OCH2(CH2)7-CO2CH3 is an acceptor for the rat liver beta-D-Gal-(1-->3/4)-D-Glc-NAc
      alpha 2,3- and beta-D-Gal-(1-->4)-D-GlcNAc alpha 2,6-sialyltransferases. Among
      the structures obtained is the terminal hexasaccharide of the CD-65/VIM-2
      epitope.

PMID- 8143288
TI  - Use of human-milk fucosyltransferase in the chemoenzymic synthesis of analogues
      of the sialyl Lewis(a) and sialyl Lewis(x) tetrasaccharides modified at the C-2
      position of the reducing unit.
AB  - Two series of trisaccharides, having the formulas alpha-Neu5Ac-(2-->3)-beta-D-Gal
      (1-->4)-beta-D-GlcZ-OR and alpha-Neu5Ac-(2-->3)-beta-D-Gal-(1-->3)-beta-D-GlcZ-OR
      [R = (CH2)8CO2CH3] respectively, in which the 2-deoxy substituent Z is azido,
      amino, propionamido, or acetamido, were prepared by chemical synthesis. Both
      types of modified trisaccharides are acceptors for a fucosyltransferase
      preparation obtained from human milk. Preparative fucosylations using this enzyme
      provided analogues of the sialyl Lewis(x) and sialyl Lewis(a) tetrasaccharide
      structures, which have been proposed to be ligands for cell-adhesion molecules.
      These syntheses further demonstrate the utility of glycosyltransferases in the
      preparation of oligosaccharide analogues.

PMID- 8143289
TI  - Synthesis and inhibition studies of C-(D-glycopyranosyl)methylamines.

PMID- 8143290
TI  - [Synthesis of 2-acetamido-1,4-imino-1,2,4-tridesoxy-D-galactitol and competitive
      inhibition of human lysosomal beta-hexosaminidase A].
AB  - The synthesis of 2-acetamido-1,4-imino-1,2,4-trideoxy-D-galactitol (1; 2
      acetamido-4-amino-1,4-anhydro-2,4-dideoxy-D-galactitol) by two different routes
      starting from 2-acetamido-2-deoxy-D-glucose is described. Compound 1 is a
      competitive inhibitor of human lysosomal beta-hexosaminidase A with K(i) values
      of 18 microM (beta-subunit) and 220 microM (alpha-subunit). Similar properties
      were found for the already known 2-acetamido-2-deoxy-D-gluco-hydroximo-1,4
      lactone.

PMID- 8143291
TI  - N-bromoacetyl-glycopyranosylamines as affinity labels for a beta-glucosidase and
      a cellulase.

PMID- 8143292
TI  - Hydrolysis of glycosylpyridinium ions by anomeric-configuration-inverting
      glycosidases.
AB  - The hydrolyses of five beta-D-xylopyranosylpyridinium ions by the beta-D
      xylosidase of Bacillus pumilus proceed with kcat values 10(8)-10(9)-fold larger
      than the rates of spontaneous hydrolysis of the same compounds. Log(kcat) values
      correlate well with aglycon pK(a) [B1g(V) = -0.52, r = 0.99], whereas the
      correlation of log(kcat/Km) is poor [r = 0.77; beta 1g(V/K) = approximately 
      0.6]. The (1-->3)-beta-D-glucanase of Sporotrichum dimorphosporum hydrolyses 4
      bromo-2-(beta-D-glucopyranosyl)isoquinolinium ion with a rate enhancement of
      10(8). The amyloglucosidase II of Aspergillus niger hydrolyses three alpha-D
      glucopyranosylpyridinium ions with rate enhancements of 10(5)-10(8). The
      efficient hydrolysis of glycosylpyridinium ions by these three inverting
      glycosidases, the catalytic mechanism of which is unlikely to involve a
      nucleophile from the enzyme, makes it improbable that the hydrolysis of
      glycosylpyridinium ions by retaining glycosidases, discovered some years ago, is
      initiated by addition of a catalytic nucleophilic carboxylate group of the enzyme
      to the pyridinium ring.

PMID- 8143293
TI  - Substrate recognition by amyloglucosidase: evaluation of conformationally biased
      isomaltosides.
AB  - Amyloglucosidase catalyzes the hydrolysis of methyl beta-maltoside (1) 30-50
      times more rapidly than methyl alpha-isomaltoside (2). It is established that OH
      6', OH-4', and OH-4 which are involved in key polar interactions with the enzyme
      in the case of isomaltoside. Conformational analyses based on HSEA calculations
      indicate that the dispositions in space of OH-3 of maltose relative to OH-4' and
      OH-6' in the preferred conformation for the maltoside (1) is energetically more
      readily achieved by methyl 6R-C-methyl-alpha-isomaltoside (3), than for its 6-S
      isomer (4). A kinetic evaluation of the hydrolysis in fact has shown that the R
      compound is more strongly bound by the enzyme (Km = 0.9 mM) than the parent
      isomaltoside (Km = 24.5 mM), whereas the S-compound has the weakest enzyme
      binding (Km = 90 mM). Since the kcat values were all within the range 0.85 +/-
      0.20 s-1, it is evident that the relative rates of hydrolysis are related to the
      relative ease for the compounds to achieve an interaction of a hydroxyl group in
      the aglycon of an alpha-D-glucopyranoside with the enzyme for the formation of
      the enzyme-substrate complex. The relative rates of hydrolysis of the alpha
      glucosides of the 1,3-dihydroxy-trans-decalins, 5 and 6, provide further support
      for this highly desirable but not necessary recognition for the orientation of
      the reducing glucose unit in the active site.

PMID- 8143294
TI  - Converting enzyme inhibitors in cardiovascular therapy: current status and future
      potential.

PMID- 8143295
TI  - Angiotensin converting enzyme inhibitors and cardiovascular remodelling.
AB  - Regional alterations in left ventricular function are generally present in
      patients who sustain an acute myocardial infarction. Segmental wall motion
      abnormalities in left ventricular systolic function can be identified in the
      hyperacute period and generally persist in patients with myocardial infarction.
      Through the process of infarct expansion, the infarcted territory may thin and
      lengthen in the short term following a myocardial infarction. Some infarct
      survivors are also prone to further progressive alterations in the shape and size
      of the left ventricle, a process that has been termed "postinfarction ventricular
      remodelling". Although a component of left ventricular remodelling appears to
      represent an adaptive process serving to preserve stroke volume and cardiac
      output following myocardial injury, the enlargement process may have undesirable
      long term effects on global left ventricular function and on clinical prognosis.
      Fortunately, recent experimental and clinical evidence shows that ventricular
      remodelling and its deleterious consequences may be preventable.

PMID- 8143296
TI  - Endothelial protection by converting enzyme inhibitors.

PMID- 8143297
TI  - Antiarrhythmic effects of ACE inhibitors: a matter of faith or reality?

PMID- 8143298
TI  - Cardioprotection by angiotensin converting enzyme inhibitors--the experimental
      evidence.

PMID- 8143299
TI  - Inhibition of ACE/kininase-II, acute myocardial infarction, and survival.
AB  - Three major trials, in patients with chronic heart failure, have shown that
      treatment with an ACE inhibitor reduces mortality. However, at the time of
      writing this review there continue to be strong grounds for uncertainty as to the
      role of these drugs after acute myocardial infarction in man. This uncertainty is
      exemplified by the findings of two recently published mortality trials, the
      CONSENSUS II and the SAVE investigations. Despite virtually identical premises,
      though widely differing therapeutic approaches, the observations reported in
      these two papers contrast markedly. In this review we have sought to analyse the
      possible reasons why the findings of the two trials differ. In our attempt to
      understand this important issue we have necessarily turned to smaller clinical
      studies, and also to investigations performed in animals. Furthermore, we review
      the investigational strategies which have been employed by other, currently
      unreported, large scale survival studies, as these will certainly hold many of
      the answers to the questions which the SAVE and CONSENSUS II trials have raised.

PMID- 8143300
TI  - Inhibition of ACE/Kininase-II after myocardial infarction--addendum.

PMID- 8143301
TI  - Fosinoprilate prolongs the action potential: reduction of iK and enhancement of
      the L-type calcium current in guinea pig ventricular myocytes.
AB  - OBJECTIVE: The aim was to study the effect of fosinoprilate, a new ACE inhibitor,
      on the action potential and plateau currents of cardiac muscle. METHODS: Whole
      cell patch technique was used to record action potentials (n = 6), the L-type iCa
      (iCaL; n = 5), in some cases (n = 4) also using Cs+ loaded pipettes; with 5 mM
      Co2+, the time dependent K+ current (IK) underlying delayed rectification was
      analysed in guinea pig ventricular myocytes (n = 3). RESULTS: Fosinoprilate
      prolonged the 50% repolarisation (APD50) from 440(SEM 50) ms to 485(48) ms (0.1
      microM), to 525(46) ms (0.3 microM), to 632(58) ms (1 microM), and to 702(69) ms
      (3.0 microM). The APD90 was delayed from 510(63) ms to 540(45) ms (0.1 microM),
      to 583(42) ms (0.3 microM), to 702(62) ms (1.0 microM), and to 765(72) ms (3.0
      microM). Higher concentrations (10-100 microM) caused early afterdepolarisations,
      very long action potentials, and irregular oscillations. ICaL was enhanced by up
      to 183%, showing a Kd of 0.2 microM; in contrast to the steady state activation
      (d infinity), the inactivation curve f infinity was shifted in the depolarising
      direction, considerably enlarging the Ca2+ window. Slow inactivation time course
      was unchanged, whereas the fast time constant (tau f) was accelerated.
      Fosinoprilate reduced the outward current during depolarising clamps from
      1.7(0.2) nA to 1.41(0.11) nA with a 0.1 microM dose, and to 0.54(0.14) nA with a
      1.0 microM dose; the tails were decreased from 0.39(0.03) nA to 0.27(0.03) nA
      with 0.1 microM and to 0.13(0.02) nA with 1.0 microM. Kinetics of IK were
      unaltered. Computer simulations based on these data using the OXSOFT-HEART
      program mimicked the results rather closely. CONCLUSIONS: The results suggest
      that fosinoprilate prolongs the plateau due to a partial block of iK and an
      extension of the Ca2+ window by 10 mV, causing a class III antiarrhythmic effect.
      High concentrations further open the Ca2+ window resulting in early
      afterdepolarisations and plateau oscillations and may cause an inward transport
      of Ca2+ ions by the Na-Ca exchange.

PMID- 8143302
TI  - Endothelium dependent vasomotor responses to endogenous agonists are potentiated
      following ACE inhibition by a bradykinin dependent mechanism.
AB  - OBJECTIVE: The aim was to investigate the effects of angiotensin converting
      enzyme inhibition on agonist induced endothelium dependent vasodilatation in
      vivo. METHODS: Chronically instrumented conscious dogs (n = 8) were prepared for
      the measurement of coronary blood flow, diameter of the left circumflex coronary
      artery, mean arterial blood pressure, and heart rate. Intracoronary infusions of
      acetylcholine, adenosine, and bradykinin that induced dose dependent increases in
      coronary blood flow and diameter were performed with and without intracoronary
      administration of captopril (1 mg.kg-1) and enalapril (0.4 mg.kg-1). The effects
      were studied of concomitant inhibition of bradykinin actions by the specific B2
      kinin antagonist HOE-140 (10(-7) M), NO-synthesis by NG-nitro-L-arginine-methyl
      ester (L-NAME, 2 x 10(-5) M), or cyclo-oxygenase by indomethacin (10(-7) M) (all
      intracoronary). RESULTS: Neither captopril nor enalapril had significant
      vasodilating effect on the coronary vasculature when given alone. In contrast,
      both ACE inhibitors potentiated the agonist induced increases in coronary blood
      flow by bradykinin and acetylcholine (p < or = 0.01). HOE-140 strongly
      antagonised the effects of infused bradykinin and prevented the potentiation of
      acetylcholine responses by ACE inhibition. L-NAME caused hypertension and
      bradycardia and abolished the responses to acetylcholine and adenosine, but only
      partially attenuated the bradykinin induced increases in coronary blood flow.
      Simultaneous ACE inhibition reduced the hypertensive effect of L-NAME and
      partially restored the responses to bradykinin. Indomethacin reduced the
      responses to bradykinin but did not affect acetylcholine and adenosine induced
      coronary vasodilatation. The potentiation of the response to acetylcholine
      induced by ACE inhibition was, however, diminished by indomethacin. CONCLUSIONS:
      In the coronary vasculature of the dog, ACE inhibitors enhance vasomotor
      responses to endothelium dependent agonists by facilitating the release of both
      NO and PGI2, a mechanism which is coupled to endogenously formed bradykinin. ACE
      inhibitors may thus mediate their effects in vivo partly by increasing the
      capacity of the endothelium to release autacoids.

PMID- 8143303
TI  - Decreased lumen size after balloon injury despite inhibition of neointimal
      thickening and antivasospastic treatment.
AB  - OBJECTIVE: Both calcium antagonists and angiotensin converting enzyme (ACE)
      inhibitors are known to diminish the development of intimal thickening after a
      balloon catheter lesion. It was previously shown that narrowing of carotid artery
      lumen induced by balloon injury was not influenced by treatment, even though the
      two ACE inhibitors used inhibited neointimal thickening. The aim of the present
      study was to include a calcium antagonist as well, in order to investigate
      whether vasospasm contributes to the persistence of lumen narrowing in ACE
      inhibitor treated rats after a balloon lesion. METHODS: Six groups of 10 rats
      were subject to balloon lesion of the left carotid artery. They received
      spirapril (10 mg.kg-1 x d-1) or isradipine (30 or 100 mg.kg-1 x d-1) or both,
      given throughout the study in the food. Controls received no drug. Neointimal
      thickening was measured histologically two weeks after injury. The cross
      sectional carotid lumen area was measured in vivo by nuclear magnetic resonance
      imaging, both before and two weeks after balloon injury, and also postmortem by
      histological techniques. RESULTS: Two weeks after injury, the lumen area of the
      left carotid artery was significantly reduced following balloon injury, as
      measured by both techniques. Treatment did not modify the stenosis process as
      assessed by either method for measuring lumen size. Neointimal thickening,
      however, was inhibited by between 4% (low dose isradipine) and 59% (combined
      spirapril + high dose isradipine) in the various treatment groups. CONCLUSIONS:
      Since calcium antagonist treatment was not able to influence the reduction of
      lumen size, it is unlikely that the narrowing is due to reversible spasm of the
      carotid artery in the first two weeks after inducing a balloon lesion.
      Alternatively, chronic vasospasm of neointimal smooth muscle might not be very
      sensitive to calcium antagonists.

PMID- 8143304
TI  - Prolongation by captopril of action potential duration in the normal and
      hypertrophied rat ventricle: direct action or inhibition of the local angiotensin
      converting enzyme?
AB  - OBJECTIVE: The aims were: (1) to study the acute effects of captopril on the
      action potential characteristics of ventricular fibres from the normal rat, (2)
      to compare the effects of captopril with those of perindoprilat, a non-thiol
      angiotensin I converting enzyme (ACE) inhibitor, (3) to determine the
      electrophysiological properties of the peptide substrates of converting enzyme,
      bradykinin and angiotensin I, and (4) to investigate whether the effects of
      captopril occurring in the healthy heart also occur in two models of ventricular
      hypertrophy. METHODS: Action potentials were recorded with the standard glass
      microelectrode technique in right ventricular preparations excised from rat
      hearts and superfused under baseline conditions and with drug containing or
      peptide containing Tyrode solution. Ventricular hypertrophy was induced in
      response to hypertension (unilaterally nephrectomised, DOCA-salt model) or 4 week
      old left ventricular infarction. RESULTS: In preparations from normal rat hearts,
      captopril increased action potential duration in a concentration dependent
      fashion [EC50 = 3.5 x 10(-8) M; maximum effect = 44(SEM 5.1)% prolongation at 10(
      5) M for action potential duration at 90% repolarisation, APD90]. Perindoprilat
      similarly caused a dose dependent increase in action potential duration, but with
      100 times greater potency [EC50 = 3.1 x 10(-10) M; maximum effect = 71(11)%
      prolongation at 10(-5) M for APD90]. SQ 14,534, a stereoisomer of captopril with
      one hundredth the ACE inhibitor potency, had no significant effect on action
      potential duration at 10(-5) M. Angiotensin I and bradykinin caused concentration
      dependent prolongation of action potential, but angiotensin II (10(-6) M) had no
      effect. Captopril (10(-5) M) had no significant effect in the hypertrophied right
      ventricle from DOCA-salt hypertensive rats, but significantly increased APD90
      [39(4.9)%] in right ventricular preparations from rats with 4 week old anterior
      left ventricular infarction. CONCLUSIONS: In the rat, captopril prolongs action
      potential duration, an effect possibly due to local accumulation of bradykinin
      and angiotensin I.

PMID- 8143305
TI  - Accounting for the Gregg effect in tetanised coronary arterial pressure-flow
      relationships.
AB  - OBJECTIVE: Myocardial contraction shifts the diastolic coronary pressure-flow
      relationship to lower flows at any given pressure, the amount of shift being
      determined primarily by the contractile level. A portion of this shift may be
      attributable to the Gregg effect. The purpose of this study was to quantify the
      influence of the Gregg effect and thereby demonstrate the pure effect of
      activation at a constant contractile level on the pressure-flow relationships.
      METHODS: It was first shown in beating canine interventricular septa that
      transverse stiffness induced by small high frequency indentations transverse to
      the plane of the tissue was an index of contractility. At constant perfusion
      pressure and preload, there was an inverse relationship between peak transverse
      stiffness and contractile level (induced by graded doses of 2,3-butanedione
      monoxime) for both isotonic and auxotonic contractions. A Gregg effect was next
      verified by showing a linear dependence between transverse stiffness and
      perfusion pressure during ryanodine induced tetanizations. Finally, the
      relationship between changes in flow and transverse stiffness was determined from
      diastole to tetany at two contractile levels. These relationships suffice to
      quantify the Gregg effect. RESULTS: Correcting for the Gregg effect from the
      transverse stiffness measurements obtained concomitantly with previously reported
      pressure-flow data in six specimens showed the following: using a linear fit to
      the pressure-flow data, the mean slope of the diastolic pressure-flow
      relationships decreased from 0.88 to 0.81 and 0.74 ml.min-1 x mmHg-1 during
      tetanisation at normal and reduced contractile levels, respectively. Correcting
      for the Gregg effect decreased the tetanised slopes to intermediate values of
      0.85 and 0.79 ml.min-1 x mmHg-1, respectively. CONCLUSIONS: A small but clearly
      discernible portion of the shift in tetanised pressure-flow relationships is
      attributable to the Gregg effect. Similar conclusions pertained when quadratic
      regressions were fitted to the pressure-flow data.

PMID- 8143306
TI  - Beneficial effects of MDL 74,405, a cardioselective water soluble alpha
      tocopherol analogue, on the recovery of function of stunned myocardium in intact
      dogs.
AB  - OBJECTIVE: Postischaemic myocardial dysfunction ("stunning") is caused in part by
      the generation of reactive oxygen species resulting in oxidant stress. The aim of
      this study was to test the hypothesis that the systemic administration of MDL
      74,405, a hydrophilic cardioselective alpha tocopherol analogue, is beneficial in
      attenuating myocardial stunning. METHODS: Open chest dogs undergoing a 15 min
      coronary artery occlusion and 4 h of reperfusion received an intravenous infusion
      of either saline (controls, n = 9) or MDL 74,405 (n = 8) at a dose of 0.3 mg.kg-1
      x h-1 starting 30 min before coronary occlusion and ending 60 min after reflow.
      RESULTS: Regional myocardial function (assessed as systolic wall thickening) was
      similar in control and treated groups at baseline and during ischaemia. Following
      reperfusion, however, the dogs treated with MDL 74,405 had significant
      improvement in the recovery of function, which was evident 2 h after restoration
      of flow and was sustained throughout the rest of the reperfusion phase. Analysis
      of covariance showed that the differences in wall thickening after reperfusion
      between the two groups were independent of collateral flow during occlusion.
      Furthermore, the enhanced recovery effected by MDL 74,405 could not be attributed
      to non-specific factors such as coronary flow after reperfusion, arterial
      pressure, heart rate, or other haemodynamic variables. Measurements of MDL 74,405
      showed that the myocardial content of the antioxidant at 4 h of reperfusion was
      approximately 30 times greater than the plasma concentration at 1 h of
      reperfusion, suggesting preferential cardiac accumulation of this drug.
      CONCLUSIONS: This study shows (1) that systemic administration of the alpha
      tocopherol analogue MDL 74,405 in the setting of myocardial ischaemia and
      reperfusion does not result in adverse cardiovascular effects, at least in the
      first few hours after injection; (2) that the drug accumulates in myocardial
      tissue at concentrations much higher than in the plasma; (3) that intravenous
      infusion of MDL 74,405 produces an attenuation of myocardial stunning comparable
      to that previously observed with intracoronary administration of other
      antioxidants; and (4) that this beneficial effect is independent of non-specific
      actions on haemodynamic variables or coronary flow. The results suggest that the
      systemic administration of hydrophilic, cardioselective alpha tocopherol
      analogues represents an effective therapeutic approach to the alleviation of
      postischaemic dysfunction.

PMID- 8143307
TI  - Series coupled non-contractile elements are functionally unimportant in the
      isolated heart.
AB  - OBJECTIVE: In order to evaluate possible artefact in interpretations of
      contractile behaviour in isolated heart experiments, the relative elastances of
      series coupled non-contractile and contractile components of the left ventricle
      of the isolated heart were evaluated. METHODS: Hearts were isolated from ferrets
      and rabbits and mounted on a servo-controlled volume regulation device. These
      hearts were made to beat isovolumetrically until a selected volume perturbation
      was introduced. Constant flow volume withdrawals at two flow values were
      performed over a period of < 20 ms centred around the time of peak isovolumetric
      pressure. Three levels of isovolumetric pressure were produced using basal,
      extrasystolic, and potentiated beats. Pressure responses to volume withdrawals at
      two flows and three isovolumetric pressures were then analysed using a
      mathematical model to evaluate relative values of series coupled contractile and
      non-contractile elastances. To validate the analysis procedure, a non-contractile
      series artefact with known elastance was coupled to the left ventricle; volume
      perturbations were then applied to the coupled left ventricle-artefact system;
      responses were analysed and the estimate of series coupled non-contractile
      elastance was compared to the known elastance of the added artefact. RESULTS: A
      wide range of isovolumetric pressures [208(SD 40) mmHg] was produced in the
      ferret with basal, extrasystolic, and potentiated beats. A lesser range of
      isovolumetric pressures [50(15) mmHg] was produced in the rabbit. The
      mathematical model fitted the data very well in both the ferret and rabbit. The
      elastance of the series coupled non-contractile component could be estimated only
      in some ferrets. When estimated in the ferret, the elastance of the series
      coupled non-contractile component was never less than 4x that of the contractile
      component. When a series artefact of sufficiently low value was coupled with the
      native left ventricle, the elastance of the non-contractile component could be
      reliably estimated in both ferrets and rabbits and the estimated value
      approximated that of the added artefact. This indicated that the elastance of the
      series coupled non-contractile component of the native left ventricle was much
      higher than that of the added artefact. CONCLUSIONS: The series coupled non
      contractile component of the isolated heart possesses a very much higher
      elastance than the contractile component. In fact, the elastance of the non
      contractile component is so great that it contributes very little to the dynamic
      behaviour of the left ventricle. Virtually all of the elastance of the left
      ventricle of the isolated heart is due to the contractile component.

PMID- 8143308
TI  - Conductance catheter measurements of left ventricular volume in the intact dog:
      parallel conductance is independent of left ventricular size.
AB  - OBJECTIVE: It has recently been suggested that conductance catheter parallel
      conductance (alpha Vc) is a function of left ventricular volume. To confirm this,
      alpha Vc was measured in this study over a wide range of steady state volumes. In
      addition, conductance derived volumes were compared to those obtained by
      radionuclide angiography to determine if the conductance catheter can be used to
      measure absolute left ventricular volume accurately in the intact dog heart.
      METHODS: Seven dogs were anaesthetised and instrumented with left ventricular
      conductance and pressure tip catheters, a flow through rho cuvette to continually
      measure blood resistance, a thermodilution catheter, and a venous catheter for
      volume infusion/withdrawal. Conductance and angiographic data were acquired at
      8(SD 1) variably loaded states. Parallel conductance was measured twice at each
      state using a saline dilution technique and a new non-linear algorithm that
      allows variability in the observations of both maximum and minimum conductance
      volumes. RESULTS: The mean value of alpha Vc was 89.1(18.0) ml (71.8 to 111.3 ml)
      with a mean within-animal coefficient of variation of 7.3(3.4)%. Multiple linear
      regression using dummy variables to account for the large interanimal variability
      did not reveal any relationship between alpha Vc and either maximum or minimum
      left ventricular volume. Furthermore, no difference was found when alpha Vc
      values measured at the lowest and highest loading levels in each dog were
      compared. Linear regression showed good agreement between conductance and
      radionuclide derived end diastolic volumes (slope = 0.94, R = 0.9, p < 0.001).
      CONCLUSIONS: While alpha Vc varies between animals, it remains constant within
      any given animal over a broad range of left ventricular volumes. Thus the
      conductance catheter can provide reliable absolute left ventricular volume
      measurements under steady state conditions.

PMID- 8143309
TI  - Identification of conduction block in cardiac muscle: in vitro observations in
      canine epicardium.
AB  - OBJECTIVE: The aim was to examine the ability of several previously proposed
      criteria and of "vector mapping" to distinguish slow conduction from conduction
      block in canine myocardium. METHODS: Two different in vitro preparations of
      canine epicardium were used. In 10 tissues, an anatomical barrier was simulated
      by a cut (five longitudinal and five transverse to fibre orientation). Eleven
      tissues removed two weeks after occlusion-reperfusion infarction were also
      studied. Isochronal activation maps were constructed from extracellular and
      intracellular recordings and vector loops formed by summing two orthogonally
      recorded bipolar electrograms were used to indicate the direction of cardiac
      activation. RESULTS: In the cut model, electrograms recorded from over the
      anatomical barrier were usually normal or showed double potentials but could
      occasionally be fractionated. Isochronal activation maps obtained from
      extracellular recordings were able to identify five of five anatomical barriers
      transverse to, but only one of five barriers longitudinal to, fibre orientation.
      The direction of cardiac activation indicated by vector loops identified
      conduction block in all 10 preparations. In 11 tissues removed from canine
      ventricles with experimental myocardial infarction, microelectrode recordings
      were used to characterise regions as either slow conduction or conduction block.
      Isochronal activation patterns obtained from extracellular recordings generally
      showed impulses proceeding through zones of conduction and around zones of
      conduction block but disagreed with the results of microelectrode impalements in
      two of 11 cases. Electrogram morphology was also not always able to distinguish
      slow conduction from block. The direction of cardiac activation determined by
      vector mapping accurately characterised all regions of tissue as showing either
      slow conduction or conduction block. CONCLUSIONS: Limited regions of conduction
      block or slow conduction are frequently present in epicardial tissues removed
      from experimental myocardial infarction. The morphology of extracellular
      electrograms and isochronal activation mapping performed from extracellular
      recordings is often but not always able to distinguish slow conduction from
      conduction block. Vector mapping is useful in distinguishing slow conduction from
      conduction block in these situations and may help evaluate myocardial conduction
      patterns.

PMID- 8143310
TI  - A1 receptor mediated myocardial infarct size reduction by endogenous adenosine is
      exerted primarily during ischaemia.
AB  - OBJECTIVE: The aim was to test the hypothesis that A1 receptor mediated
      cardioprotection by endogenous adenosine is exerted during ischaemia rather than
      reperfusion. METHODS: Anaesthetised open chest rabbits were subjected to 30 min
      regional ischaemia and 120 min reperfusion, and randomised to one of six groups:
      group I--saline vehicle (VEH) (n = 12) to allow A1 and A2 adenosine receptor
      interactions during ischaemia and reperfusion; group II--both A1 and A2 receptors
      were antagonised during ischaemia and reperfusion with 8-p
      sulphophenyltheophylline (SPT) (10 mg.kg-1) (SPTIR, n = 14); groups III and IV-
      the selective A1 adenosine receptor antagonist 8-(3-noradamantyl)-1,3
      dipropylxanthine (KW-3902) was given during ischaemia-reperfusion in low dose (1
      mg.kg-1, LA1-IR, n = 11) and higher dose (2 mg.kg-1, HA1-IR, n = 6); group V--KW
      3902 (1 mg.kg-1) was given only during reperfusion (A1-R, n = 12); group VI--SPT
      was given only at reperfusion (SPTR, n = 11). RESULTS: In in vitro studies, (1)
      KW-3902 completely inhibited negative inotropic effects of the A1 agonist R(-)N6
      (2-phenylisopropyl) adenosine (R-PIA) in catecholamine stimulated papillary
      muscles, and (2) had no effect on concentration dependent vasorelaxation to
      adenosine or R-PIA. In in vivo studies, transmural myocardial blood flow in the
      area at risk (determined using 15 microns radiolabelled microspheres) was reduced
      by 98% in all groups from 139(SEM 15.8) to 2.7(1.1) ml.min-1 x 100 g-1 (p <
      0.001). At 120 min of reperfusion, blood flow in the area of necrosis was
      significantly less in groups LA1-IR [48.6(6.2)], HA1-IR [36.1(7.1)], SPTIR
      [35.9(6.4)], and SPTR [25.1(5.4)] compared to groups VEH [69.1(15.8)] and A1-R
      [77.2(11.8)]. The area at risk (Ar) was equivalent among groups. SPT treatment
      during ischaemia-reperfusion in the SPTIR group increased the area of necrosis
      (An, assessed by triphenyltetrazolium chloride) relative to Ar (An/Ar) to
      51(1.9)% v 26.0(1.7)% in VEH group. KW-3902 in LA1-IR and HA1-IR during both
      ischaemia and reperfusion increased An/Ar to 35.2(2.5)% and 35.2(2.1)% of area at
      risk, respectively, both of which were significantly less than the SPTIR group.
      With A1 blockade at reperfusion (A1-R), An/Ar was equivalent to that in VEH
      [27.0(1.9)%], while an infarct size of 46.7(2.1)% was still observed in SPTR.
      CONCLUSIONS: While adenosine exerts its predominant modulation of infarct size
      during reperfusion, the cardioprotection mediated by A1 receptor mechanisms is
      modest and exerted principally during the ischaemic time period.

PMID- 8143311
TI  - How to isolate cardiac myocytes.
AB  - A complete technique is described for the isolation of myocytes from mammalian
      hearts using the Langendorff perfusion technique. The use of calcium-free
      solution containing collagenase and protease, followed by low calcium solution,
      consistently results in a large number of calcium tolerant myocytes which are
      well suited for long periods of electrophysiological recording.

PMID- 8143312
TI  - Drugs that alter nitric oxide homeostasis: a reply.

PMID- 8143313
TI  - Heart rate and athletic training.

PMID- 8143314
TI  - Effect of reperfusion on 111In-antimyosin monoclonal antibody uptake.

PMID- 8143315
TI  - Therapeutic modulation of ATP sensitive potassium channels in ischaemia.

PMID- 8143316
TI  - [The survey on arsenism caused by drinking water].
AB  - This paper reports the epidemiologic and clinical observations on arsenism caused
      by drinking water in Zhi Ji Liang and Tie Men Gen, Huhhot. Results showed that
      the content of arsenic in drinking water was eleven times as much as that of the
      national standard. The incidence rate of arsenism increased with the rise of
      arsenic content in water. In contrast to the high As content, the contents of Pb,
      Zn, Se were low in water and the pH value was slightly acidic. Arsenic contents
      in hair, fingernails and urine were all higher than those of the control.
      Patients with arsenism showed symptoms of anaemia.

PMID- 8143317
TI  - [Application of HBV gene subtyping method in study on familial transmission].
AB  - A cross-section epidemiological study for hepatitis B was conducted in the
      population of a village in Hebei Province. The prevalence rate of HBsAg was 3.75%
      (22/586), and HBV infection rate, 27.65% (162/586), without significant
      difference between males and females; and increasing with age. This village
      belongs to a low HBV incidence region in China. This phenomenon might possibly be
      related to the characteristic of the population (mostly blood donors) and high
      incidence of HCV (prevalence rate of anti-HCV was 10.31%, 59/572). The anti-HBc
      and overall HBV infection rate showed family clustering by binomial distribution
      analysis. The family clustering of HBV infection resulted mainly from the
      transmission from parents to their children and among the children. The overall
      positivity rate of HBV DNA was 24.77% (27/109), and the majority of the family
      members belonged to the same subtypes (72.22%). On the basis of HBV subtyping,
      familial transmission of HBV was classified into six types, ie. generational,
      horizontal, recessive, intra- and extra-familial, non-familial and undetermined
      ones.

PMID- 8143318
TI  - [Evaluation of surveillance on the case fatality rates in patients with severe
      hepatitis and of its clinical application].
AB  - The prognosis of patients with severe hepatitis is related to the severity of the
      disease when they are admitted to hospital. We retrospectively analyzed the
      clinical and laboratory data of 201 cases of severe hepatitis with the method of
      logistic regression and had obtained 8 independent variables strongly affecting
      the prognosis to form the multiple regression discriminant equation. The eight
      independent variables are Pa, A/G, SB, BUN, Cr, hepatic encephalopathy, infection
      and digestive tract bleeding. We can get the values of care fatality rates from
      the equation. The degree of severity can be classified with the value. Treatment
      plans can be drawn out and clinical research grouping can be improved on the
      basis of the values.

PMID- 8143319
TI  - [An epidemiologic study on the etiology of primary hepatocellular carcinoma in
      Shaanxi].
AB  - The result of a matched case-control study on 110 cases of primary hepatocellular
      carcinoma (PHC) in Shaanxi is reported. It was shown that HBV was closely
      associated with PHC. Besides, psychosocial and genetics factors could be risk
      factors. Vegetables and fruits might be protective factors. Synergistic action
      between HBV and inheritance and foods was observed. Logistic regression analysis
      showed that HBV infection and negative events were possibly the risk factors,
      while vegetables and fruits were probably the protective factors.

PMID- 8143320
TI  - [The significance of multiple infections with HBV, HCV and HDV in patients with
      chronic liver diseases].
AB  - Serum samples from 127 patients with chronic liver diseases (CLD) were tested for
      HBV markers, anti-HCV and HDV markers by enzyme-linked immunosorbent assay
      (ELISA). The serum samples from some patients were detected for HCV-RNA by
      reverse transcription and polymerase chain reaction (RT-PCR) technique. The
      results showed that 85.7% of chronic persistent hepatitis (CPH), 71.0% of chronic
      active hepatitis (CAH) and 73.9% of liver cirrhosis (LC) were caused by HBV
      infection only. In 127 patients with CLD, 37 (29.1%) were multiple infections
      with HBV, HCV and HDV. The incidence of patients with chronic severe hepatitis
      (CSH) was significantly higher in multiple infections than in HBV infection only
      (P < 0.05). 74.2% of CSH were caused by multiple infections. The average levels
      of serum bilirubin and prothrombin time in patients with CSH caused by multiple
      infections were significantly higher than those in patients caused by HBV
      infection only (P < 0.05). The mortality rate of patients with CSH caused by
      multiple infections was significantly higher than that of cases by HBV infection
      only (P < 0.05). Based on our data, it is concluded that multiple infections with
      HBV, HCV and HDV might be the major factor leading to the aggravation of CLD. The
      general condition and prognosis of patients with CSH caused by multiple
      infections were much worse than those of cases caused by HBV infection only. In
      China, HBV is a major agent of chronic hepatitis and liver cirrhosis.

PMID- 8143321
TI  - [Effect of population immunity against hepatitis A in day-care centers].
AB  - The authors investigated 21 groups with hepatitis A (HA) introduction into 16 day
      care centers in a district of Xi'an, studied the infection condition and the
      effect of population immunity against HA on the HA transmission. The results
      showed that when the level of population immunity prior to HA introduction was
      below 50 percent, population immunity played no significant role in the HA
      transmission.

PMID- 8143322
TI  - [Molecular epidemiologic investigation on HSV infection among married women at
      childbearing age].
AB  - By PCR and ELISA, an investigation on HSV infection of cervix was carried out
      among 120 married women. The results indicated that the total infection rate was
      23.3% (28/120). In HSV infection of cervix, HSV-2 constituted 89.3%. The positive
      rate of HSV in the cervicitis group and normal control group was 28.9% (26/90)
      and 6.7% (2/30), respectively, showing a marked difference: the positive rate in
      the group from 21 to 30 years old was 16.7% (7/43), from 31 to 40 was 34.6%
      (9/26); the positive rate in the group from rural areas was 30.8% (16/52), in the
      group from city was 17.6% (2/18).

PMID- 8143323
TI  - [Analysis of human plague episodes in Qinghai from 1958 to 1991].
AB  - One hundred and sixty four episodes of human plague including a total of 387
      cases occurred in Qinghai Province from 1958 to 1991. The average yearly number
      of episodes of plague and case fatality rate were 5 including 11.7 cases and
      54.26%, respectively. The sources of infection were Himalayan Marmota in 73.17%
      and non-rodent animal hosts in 15.85% Pneumonic type, simple bubonic type and
      septicemic type of plague accounted for 57.88%, 23.26% and 16.27%, respectively.
      However, the first case in each episode manifesting as bubonic type of plague
      accounted for 87.80%. Cases of plague appeared in April, then its number
      increased with months, and reached the peak in August. A few cases could still be
      seen in December.

PMID- 8143324
TI  - [Investigation on the correlation between the mortality of cerebrovascular
      diseases and the meteorological factors in Zhanjiang City].
AB  - The correlation of the mortality of cerebrovascular diseases in more than 1
      million population from 1987 to 1989 with meteorologic phenomena (air
      temperature, atmospheric pressure, relative humidity) was studied using
      computering simple correlation analysis in Zhanjiang City which is located in
      subtropical area, with an average air temperature between 15 degrees C and 18
      degrees C in winter. The results showed that the mortality of cerebrovascular
      diseases in winter was the highest. Mortality was in significant negative
      correlation with air temperature (r = 0.7785, P < 0.01), in significant positive
      correlation with atmospheric pressure (r = 0.7511, P < 0.01), and in no
      significant correlation with relative humidity (r = 0.1413, P > 0.05). It
      suggested that the mortality of cerebrovascular diseases in Zhanjiang City would
      significantly increase in the condition that the average air temperature is 15
      degrees C-18 degrees C, and the average atmospheric pressure is 1014-1020
      millibar in winter.

PMID- 8143325
TI  - [Detection of Helicobacter pylori in human saliva by using nested polymerase
      chain reaction].
AB  - Epidemiologic studies suggest person to person spread of Helicobacter pylori (H.
      pylori), but the exact mechanism is unknown. Spread through oral secretions has
      been suggested, however, it has proved very difficult to grow the organism from
      areas outside the stomach. A nested polymerase chain reaction (N-PCR) for the
      specific detection of H. pylori was developed with two primer pairs (nested
      primers) derived from the urease gene A of H. pylori. The N-PCR could detect all
      21 H. pylori strains, including 20 isolated strains and 1 reference strain NCTC
      14126, but could not detect other bacterial species, showing the N-PCR assay to
      be 100% specific. Tenfold serial dilution experiments revealed the detection of
      as little as 0.1 fg DNA by N-PCR. To evaluate the PCR assay for clinical samples,
      gastric biopsy and aspirate specimens were tested by N-PCR, and the results were
      compared with those of culture, urease test and histologic examination (reference
      standard, RS). Among 57 biopsy specimens, H. pylori sequence was detected by PCR
      in 39 of 39 (100%) positive tissues and in none of 18 negative tissues. H-pylori
      was detected in saliva of 11 out of 19 cases in which H. pylori was positive in
      gastric mucosa by PCR. Whereas, PCR was positive in saliva of only one out of 8
      cases in which H. pylori was negative in gastric mucosa. Six gastric aspirate
      specimens were positive by N-PCR. PCR is an accurate and sensitive method that
      can detect the presence of H. pylori without the need of culture.

PMID- 8143326
TI  - [Epidemiologic study of liver cancer in the past 20 years].

PMID- 8143327
TI  - [The effect of butylhydroxyanisole, an antioxidant, on oxidative phosphorylation
      of myocardial mitochondria in experimental ischemia].
AB  - The present paper evaluated the effect of the antioxidatively acting agent
      butylhydroxyanisole (BHA) on the oxidative and energetic processes in the
      mitochondria of the myocardium, both normal and damaged with isoprenaline. BHA
      was administered for 20 days in a daily dose of 10 mg.kg-1. Experimental necrosis
      of the myocardium was induced by a single-dose administration of a dose of 25
      mg.kg-1 s.c. The results shown in Graphs 1-7 indicate that BHA in the above
      mentioned concentration did not act protectively on the metabolic processes
      taking place in the mitochondria during experimentally induced necroses of the
      myocardium.

PMID- 8143328
TI  - [Review of studies in analytical chemistry of antidepressive agents].
AB  - The present paper summarizes the methods of determination of
      psychopharmaceuticals in body fluids, tablets and injections using the techniques
      not presented in PhBs 4. The methods reported in the present paper increase
      sensitivity, shorten the time of analysis, decrease the detection limit, and very
      often eliminate a complicated pretreatment of the sample.

PMID- 8143329
TI  - [Antibiotic activity of cortalcerone and its 7-diphenylhydrazone derivative].
AB  - The present paper investigates the antibiotic properties of the novel antifungal
      antibiotic agent cortalceron and its semisynthetic derivative cortalceron 7
      diphenylhydrazone. The MIC values were assayed by the agar diffusion method.
      Cortalceron was found to weakly inhibit the growth of E. coli and B. subtilis.
      The growth of yeast was not influenced. On i.v. administration to mice
      [correction of rats], the agent produced breathing disorders and convulsions
      which later disappeared. The diphenylhydrazine derivative of cortalceron
      inhibited the growth of most yeasts tested as well.

PMID- 8143330
TI  - Improving child survival through immunisation.

PMID- 8143331
TI  - Should we continue to use benzathine penicillin for rheumatic fever prophylaxis?

PMID- 8143332
TI  - Effect of drug treatment on electroneurological measures of peripheral nerve
      function in leprosy patients.
AB  - OBJECTIVE: To investigate whether drug treatment improves the electroneurological
      measures of affected peripheral nerve function in leprosy patients. DESIGN:
      Clinical status of patients determined on the first visit by an investigator
      administered, pre-designed questionnaire, followed by measurement of motor
      conduction velocity (MCV) and distal latency (DL) of ulnar, median, common
      peroneal and posterior tibial nerves bilaterally in patients referred
      consecutively from the dermatology unit and leprosy clinic, Teaching Hospital,
      Galle. MCV and DL measurements were repeated after 6 to 12 months of treatment.
      SETTING: Department of Physiology, Faculty of Medicine, University of Ruhuna,
      Galle. SUBJECTS: 24 diagnosed leprosy patients; tuberculoid, lepromatous and
      borderline in clinical type. INTERVENTIONS: Based on clinical typing. Tuberculoid
      (paucibacillary) type rifampicin 600 mg monthly and dapsone 100 mg daily for six
      months. Lepromatous and borderline (multibacillary) type rifampicin 600 mg and
      clofazimine 300 mg monthly and dapsone 100 mg and clofazimine 50 mg daily for 24
      months. RESULTS: DL in all 4 nerves and MCV in 3 nerves tested were significantly
      different (p > 0.001) to those for the normal population and remained so after 6
      to 12 months of treatment. The DL in the ulnar nerve showed significant
      improvement (p < 0.05) after treatment. When analysed in each patient
      individually, before and after treatment, the MCV showed an improvement in 48 to
      72% of patients and the DL in 41 to 59%, but differences were not significant.
      CONCLUSIONS: Electroneurological recovery (return to normal state) of the
      affected peripheral nerves of leprosy patients does not occur after 6 to 12
      months of drug treatment. The significant (p < 0.05) improvement (becoming
      better) of ulnar nerve DL indicates that, if at all, electroneurologically
      detectable improvement of nerve function occurs in the early stages of nerve
      damage, and that it may take longer than one year after starting treatment.

PMID- 8143333
TI  - A case control study to assess the efficacy of measles vaccine.
AB  - OBJECTIVE: To measure the efficacy of measles vaccination in a given geographical
      area. DESIGN: Population based case control study. SETTING: Medical Officer of
      Health area, Kotte. SUBJECTS: All children born after January 1985 and registered
      by the midwives of the area. RESULTS: Vaccine efficacy was 88.9%, the 95%
      confidence limits being 65.21% to 96.5%. CONCLUSION: The method described is a
      suitable alternative to the more expensive serological estimates of vaccine
      efficacy.

PMID- 8143335
TI  - Parasitic zoonoses in Sri Lanka (Part 2).

PMID- 8143334
TI  - Hyperprolactinaemia and reproductive failure.
AB  - 63 cases of hyperprolactinaemia (55 women and 8 men) were studied. Of the 55
      women, 39 presented with infertility, while five were unmarried and had menstrual
      abnormalities. All eight men were partners of an infertile union. The principal
      modes of presentation of hyperprolactinaemia in women were infertility (74.6%)
      and menstrual disorders (27.6%). Galactorrhoea was evident in 28.6% and 10.7% had
      headache. There was no significant correlation between the level of prolactin and
      the duration of amenorrhoea. Changes in pituitary gonadotrophin levels were
      observed in 30.2% of cases, the common feature being an elevated LH level.
      Treatment with bromocriptine restored normal cycles, and the incidence of
      pregnancies was 38.5%. 14 normal infants were born and one patient miscarried.

PMID- 8143336
TI  - Role of infection and exchange transfusion in fulminant hepatic failure.
AB  - We report three patients with fulminant hepatic failure following sepsis managed
      by exchange transfusion. The literature on the role of infection in the
      pathogenesis of fulminant liver failure and of exchange transfusions in its
      management is reviewed.

PMID- 8143337
TI  - Ocular injuries from flying bottle caps.
AB  - Three cases of serious eye injury are described from flying metal caps of
      carbonated drink bottles. The injuries occurred while attempting to open the
      bottle in an unconventional and dangerous way. Though injuries from flying bottle
      caps have been described before, they have occurred when the bottle exploded.
      This is the first report of eye injuries caused by bottle caps while opening and
      are similar to the injuries caused by champagne corks.

PMID- 8143338
TI  - A metal syringe holder for aspiration or injection.

PMID- 8143339
TI  - Malted milks and sugar babies.

PMID- 8143340
TI  - Levodopa, rice eating and on-off phenomenon.

PMID- 8143341
TI  - Dual specificity kinases--a new family of signal transducers.
AB  - Phosphorylation/dephosphorylation reactions are one of the dynamic mechanisms
      through which cells modulate protein activity in response to environmental
      stimuli. The eukaryotic molecules which are responsible for the phosphorylation
      of serine, threonine and tyrosine residues appear to have co-ordinately evolved
      from simple prokaryotic enzymes which primarily respond to nutritional cues. In
      multicellular eukaryotes the complexity of data transfer greatly exceeds that of
      simple bacteria. The eukaryotic cell needs to exchange information with
      neighbouring and distant sister cells. Positional, nutritional and hormonal data
      are transmitted from the extracellular milieu across the plasma membrane and into
      the cytoplasm. In certain cases the signal must pass into the nucleus or other
      subcellular organelles where it is decoded and the proper cellular response
      initiated. All of these events have been shown to have a protein kinase component
      and it seems likely that in mammalian cells over 1,000 different kinase molecules
      have evolved to form the requisite signal transducing networks. In this review we
      describe a previously unappreciated family of protein kinases, the dual
      specificity or DSK kinases, which play important roles in the regulation of
      normal cellular growth and differentiation.

PMID- 8143342
TI  - Signal transduction pathways involving the Raf proto-oncogene.
AB  - The raf genes encode for a family of cytoplasmic proteins (A-raf, B-raf and c-raf
      1) with associated serine/threonine kinase activities. Raf-1 is an important
      mediator of signals involving cell growth, transformation and differentiation. It
      is activated in response to a wide variety of extracellular stimuli such as
      insulin, nerve growth factor (NGF), platelet derived-growth factor (PDGF), and in
      response to expression of oncogenes, v-src and v-ras, in a cell-specific manner.
      Recently, the first physiological substrate for Raf-1 protein kinase was
      identified. Raf-1 was found to phosphorylate and activate Mitogen-Activated
      Protein Kinase Kinase (MEK), an activator of MAP kinase, thus linking the Raf-1
      signaling pathway with that of MAP kinase. Cell specific differences in
      signalling pathways involving Raf-1 and MAP kinase have also been discovered.
      Accumulating evidence indicates that membrane tyrosine kinases, ras, Raf-1, MEK
      and MAP kinase are interconnected via a complex network rather than via a linear
      pathway involving multiple substrates and feedback loops.

PMID- 8143343
TI  - Signal transduction by integrins and its role in the regulation of tumor growth.
AB  - It has become clear that integrins have effects on tumorigenesis that are in
      addition to their role in mediating cell adhesion during invasive and metastatic
      processes. Integrins can transduce signals from the extracellular matrix to cell
      interior, via tyrosine kinases, and possibly by other mechanisms as well. These
      integrin mediated signals contribute to control of gene expression, to regulation
      of anchorage-dependence, to cell cycle transit, and to the control of tumor
      growth.

PMID- 8143344
TI  - Calcium-mediated signal transduction: biology, biochemistry, and therapy.
AB  - The process of proliferation, invasion and metastasis is a complex one which
      involves both the autonomy of the malignant cells and their interaction with the
      cellular and extracellular environments. The way in which the tumor cells respond
      to cellular and extracellular stimuli is regulated through transduction of those
      signals and translation into cellular activity. Transmembrane signal transduction
      involves three major categories of events: ion channel activation, transmission
      through guanine nucleotide binding protein intermediates with production of
      second messengers, and phosphorylation events. A frequent common denominator of
      these different pathways is a cellular calcium homeostasis. Calcium may be both a
      result of and a regulator of many of these signal transduction pathways and has
      been shown to have a role in the regulation of proliferation, invasion, and
      metastatic potential. The understanding and application of the basic tenets of
      these pathways to tumor cell proliferation, invasion, and metastases opens a new
      target for therapeutic intervention. We have identified a novel agent, CAI, which
      through inhibition of stimulated calcium influx inhibits proliferation and
      migration in vitro, and growth and dissemination in human cancer xenografts in
      vivo. CAI offers a new approach to cancer therapy, signal transduction therapy.

PMID- 8143345
TI  - The cell cycle and the retinoblastoma protein family.
AB  - Tumor formation results from alterations in the control of normal cell
      proliferation. To further our understanding of the molecular mechanisms
      underlying the deregulation of cell proliferation much attention, over the past
      decade, has been focused on the function of proto-oncogenes. Cellular oncogenes
      are thought to be growth promoting. More recently, a class of genes known as
      tumor suppressors have come under intense study. Tumor suppressors are largely
      thought to restrain cell proliferation. The retinoblastoma protein (Rb) is one of
      a growing list of tumor suppressors. Concurrent with the study of tumor
      suppressor genes has been a rapid increase in our understanding of the cell cycle
      at the molecular level. Rb and a related protein p107 are involved in the
      processes of cell proliferation and differentiation. Each functionally interacts
      with and affects the activity of the transcription factor E2F as well as other
      transcription factors involved in cell proliferation and differentiation.
      Additionally, Rb and p107 are modified by, and/or form specific complexes with,
      several elements of the basic cell cycle machinery. Specifically, Rb and p107
      interact with and are modified by various cyclins and cyclin dependent kinases
      (cdk), some of which have been shown to be essential for cell cycle progression
      and in some cases their deregulation has been implicated in the development of
      cancer. This review will attempt to convey our current functional and mechanistic
      understanding of the biological roles Rb and p107 play in proliferation,
      development and differentiation. A knowledge of the interplay between these
      positive and negative regulators of cell proliferation and differentiation, noted
      above, is central to our understanding of human cancer.

PMID- 8143349
TI  - Ketoisocaproate infusion improves survival from experimental sepsis by an
      antioxidant mechanism.
AB  - Sepsis was induced in rats by cecal ligation and puncture. A nutrient mixture was
      infused that also contained either (A) sodium 2-ketoisocaproate (NaKIC) or (B)
      NaHCO3, at 18.75 mmol kg/day. In group A, 34 of 43 rats (79%) survived, while
      only 24 of 44 rats (55%) in group B survived (P < 0.02). In a second experiment,
      cecal ligation and puncture were performed 1 week after bilateral adrenalectomy
      or sham adrenalectomy. All adrenalectomized rats died within 2 days of CLP,
      whether corticosterone replacement level was low, normal, or high. Four of eight
      sham-adrenalectomized rats receiving NaHCO3 died, but none of seven receiving
      NaKIC died. Combining both experiments by ANOVA, the effect of KIC on survival in
      adrenal-intact animals is highly significant (P = 0.002). In NaKIC-infused rats,
      blood level of pyruvate was higher on day 5 (P < 0.01), and plasma as well as
      blood levels of oxidized glutathione and ratio of oxidized/reduced glutathione
      were significantly lower. We conclude that KIC infusion improves survival of
      septic rats by an antioxidant mechanism, probably involving reaction with
      hydrogen peroxide.

PMID- 8143346
TI  - The Ras signal transduction pathway.
AB  - Considerable progress has been made over the past year in elucidating the
      mechanisms by which extracellular signals are transduced via cell surface
      receptors to trigger changes in gene expression which determine the growth and
      differentiated state of a cell. In particular, Ras proteins have been implicated
      as key intermediates that mediate the signal from upstream tyrosine kinases to a
      downstream cascade of serine/threonine kinases, which then activate nuclear
      factors that control gene expression and protein synthesis. How Ras proteins
      function is regulated in this role as a molecular switch, and how the signal is
      transmitted between the various components of the pathway, are now being
      determined. Finally, the Rho family of Ras-related proteins, which regulate the
      actin cytoskeleton, have also been implicated as mediators of oncogenic Ras
      transformation. The brisk pace at which the key components of Ras-mediated signal
      transduction pathways are being identified hold great promise that new targets
      for therapeutic intervention in cancer may now be identified.

PMID- 8143347
TI  - Focal adhesion as a signal transduction organelle.

PMID- 8143350
TI  - Systemic and regional hemodynamic changes during endotoxin or platelet activating
      factor (PAF)-induced shock in rats.
AB  - To evaluate the role of platelet activating factor (PAF) during endotoxin shock,
      we compared its effects with those of endotoxin. We measured arterial pressure
      (MAP), heart rate (HR), cardiac output (CO; thermodilution), arterial lactate
      (Calact), organ blood flow (radioactive microspheres), and organ vascular
      resistance in four groups of anesthetized (pentobarbital) male Wistar rats (n = 7
      per group), infused from t = 0 to t = 60 min with saline (group C: time matched
      control), endotoxin Escherichia coli O127:B8, 8 mg.kg-1 (group E), a "low PAF
      dose" (1 microgram.kg-1) to cause the same decrease in MAP as in group E (group
      PL), or a "high PAF dose" (3 micrograms.kg-1) to cause the same decrease in CO as
      in group E (group PH). At t = 60 min, MAP had decreased by 33% in E and PL, and
      by 55% in PH group. CO had decreased by 41% in the E and PH group. Calact had
      increased in the E and PH group by 300 and 200%, respectively. In the E, PL and
      PH group, coronary vascular resistance decreased. In the splanchnic organs,
      endotoxin caused a decrease in blood flow due to vasoconstriction, whereas PAF
      (both concentrations) caused vasodilation (except for spleen). Renal vascular
      resistance decreased (P < 0.05) in the PL group. In all groups, vascular
      resistance had increased (P < 0.05) in skin, and not changed in skeletal muscle
      (P < 0.05). Thus, hemodynamic changes after PAF infusion were partially similar
      to those after endotoxin infusion (coronary vasodilation and vasoconstriction in
      spleen and skin).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143351
TI  - Electrophysiologic properties of isolated adult cardiomyocytes from septic rats.
AB  - In this study, we examined the effect of sepsis on the electrical properties of
      isolated ventricular myocytes. Sepsis was induced by cecal ligation and puncture
      (CLP). The control rats were sham-operated. Membrane potentials and ionic
      currents in isolated cardiac myocytes were measured by the tight-seal, whole-cell
      patch-clamp technique. The results show that the resting membrane potentials of
      heart cells were significantly lower in the septic group (18 hr post-CLP) than
      those in the control group. However, there was no significant difference in
      action potential duration of 50% and 90% repolarization between the two groups of
      cells. In voltage-clamp experiments, isoproterenol (10 nM), a beta-adrenergic
      agonist, caused an increase in L-type calcium current (ICa,L) in a similar
      magnitude in myocytes isolated from the control and septic rats. Furthermore,
      isoproterenol failed to modify the time constants for ICa,L inactivation and the
      overall shape of current-voltage relationship for both groups of cells. These
      results indicate that formation of a G omega seal and subsequent tight-seal whole
      cell recording with patch-clamp technique can be performed in heart cells derived
      from CLP-induced septic rats, and that septic rat heart is capable of responding
      effectively to beta-adrenergic stimulation.

PMID- 8143348
TI  - Inhibitors of phosphatidylinositol signalling as antiproliferative agents.
AB  - Intracellular signalling pathways mediating the effects of oncogenes on cell
      growth and transformation offer novel targets for the development of anticancer
      drugs. With this approach it may be sufficient to target a component of the
      signalling pathway activated by the oncogene rather than the oncogene product
      itself. Phosphatidylinositol (PtdIns) is a key component of two growth factor
      signalling pathways. It acts as a substrate for PtdIns specific phospholipase C
      (PtdInsPLC) and for PtdIns-3-kinase. In this review the antiproliferative
      properties of some inhibitors of PtdInsPLC and PtdIns-3-kinase are considered.
      There are some compounds already in clinical trial as anticancer drugs that may
      act by inhibiting PtdIns signalling, as well as several compounds in preclinical
      development. Some problems that may be encountered in developing this new class
      of anticancer drugs are discussed.

PMID- 8143352
TI  - Macrophage treatment in suckling rat endotoxic shock.
AB  - Gram-negative sepsis/septic shock in the human newborn continues to be a severe
      medical problem because of significant mortality and morbidity. Since macrophages
      detoxify endotoxin, a decreased number of macrophages may contribute to the
      newborn's sensitivity to endotoxin. In this study, peritoneal macrophages were
      used for the treatment of endotoxic shock in 10-day-old rats, and 24-hr
      mortality, plasma glucose, and lactate concentrations were monitored. Peritoneal
      macrophages were harvested from adult or 10-day-old rats. Caseinate-stimulated
      macrophages from adult and 10-day-old rats significantly decreased the mortality
      of 10-day-old rat endotoxic shock from 90% to 37.5% and 44.4%, respectively.
      Resident macrophages from adult and 10-day-old rats also decreased the mortality
      from 90% to 12.5% and 45.4%, respectively. Peritoneal macrophages from adult rats
      significantly ameliorated hypoglycemia during endotoxic shock in a dose-dependent
      manner. Macrophage treatment decreased plasma endotoxin concentration (P < 0.05).
      Macrophage treatment was important for host defense.

PMID- 8143353
TI  - Subcutaneous and gut tissue perfusion and oxygenation changes as related to
      oxygen transport in experimental peritonitis.
AB  - Peritonitis and septic shock may lead to tissue hypoxia, but this risk is not
      identical in all organ systems. This study was undertaken to measure changes in
      tissue oxygenation and perfusion in the gut wall and subcutaneous tissue,
      respectively, and to examine their relation to oxygen delivery and consumption.
      Twelve pigs were anesthesized and mechanically ventilated. An ultrasonic flow
      probe was placed around the superior mesenteric artery for registration of blood
      flow. A mesenteric vein was cannulated for blood sampling. For calculation of gut
      intramural pH (pHi), a Silastic balloon (Tonomitor) was placed in the lumen of
      the midileum. pHi was calculated from tonometrically measured PCO2 and arterial
      bicarbonate concentration. The subcutaneous PO2 was measured by means of an
      oxygen-permeable Silastic tube implanted in the subcutis of the abdominal wall.
      Oxygen delivery (DO2) and consumption (VO2) were determined for the gut as well
      as for the whole body. In six randomly allocated animals, peritonitis was induced
      after a stabilization period of at least 1 hr, by instillation of autologous
      faeces into the abdominal cavity, while the other six animals served as controls.
      The animals were then followed for 5 hr. pHi remained stable in the control
      group, whereas a drop from 7.37 to 7.02 took place in the peritonitis group. In
      the test group, subcutaneous oxygen tension (PscO2) already began to fall 1 hr
      after the induction of peritonitis, and gained the minimum at the end of the
      study. In peritonitis, a moderate correlation was seen between pHi and DO2 (r =
      0.51 +/- 0.16); no statistical difference was noted if pHi was correlated to gut
      DO2 (r = 0.56 +/- 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143354
TI  - Increase in the plasma concentration of reduced glutathione observed in rats with
      liver damage induced by lipopolysaccharide/D-galactosamine: effects of
      ulinastatin, a urinary trypsin inhibitor.
AB  - The changes in plasma concentrations of reduced glutathione were investigated in
      rats with endotoxin hepatitis. An increase in serum alanine aminotransferase
      activity and in serum total bilirubin concentration was observed 12 hr after the
      intraperitoneal co-administration of small doses of Escherichia coli
      lipopolysaccharide and D-galactosamine in starved rats. At the same time, an
      increase in the plasma concentration of reduced glutathione was also observed.
      The increase in reduced glutathione from 14 +/- 2 to 20 +/- 9 microM (n = 11, P <
      0.05) correlated well with that in serum alanine aminotransferase activity.
      Ulinastatin, a potent inhibitor of polymorphonuclear leukocyte elastase,
      partially counteracted all of these changes. Ulinastatin also reduced
      histological liver damage induced by endotoxin. We conclude that the increase in
      the plasma concentration of reduced glutathione reflects hepatocellular damage
      associated with endotoxin hepatitis. The partial reversal of the damage by
      ulinastatin is consistent with the proposal that the activation of
      polymorphonuclear leukocytes is involved in endotoxin hepatitis.

PMID- 8143355
TI  - Comparative drug influence on peroxide mediated increase of cytosolic calcium in
      human endothelial cells.
AB  - The increase of cytosolic free calcium in human umbilical vein endothelial cells
      caused by peroxides was used as a model to determine and compare the putative
      cytoprotective properties of substances known to interfere with the generation or
      metabolism of reactive oxygen species. Hydrophilic hydrogen peroxide and
      lipophilic cumene hydroperoxide were used as sources of reactive oxygen. [Ca2+]i
      in endothelial cells was measured by the FURA method and the resting level was
      found to be 129.3 +/- 14.1 nM. Both peroxides were found to increase cytosolic
      calcium with dependence on the concentration and on the presence of extracellular
      calcium. Among the substances tested, only catalase and N-acetyl-cysteine were
      able to exhibit a significant cytoprotective effect.

PMID- 8143356
TI  - Bilirubin inhibits protein kinase C activity and protein kinase C-mediated
      phosphorylation of endogenous substrates in human skin fibroblasts.
AB  - The primary target and molecular basis of bilirubin toxicity to cellular function
      are not known. We have studied the effect of bilirubin on protein kinase C
      activity in subcellular fractions of human skin fibroblasts and on protein kinase
      C-mediated phosphorylation of endogenous substrates. Bilirubin inhibited the
      kinase activity in a concentration-dependent manner: a 50% inhibition was
      achieved by 45 mumol/l in the homogenate and 75 mumol/l in both the cytosolic and
      membranous fractions. Inhibition of protein kinase C activity by bilirubin was
      reversed by increasing the concentrations of activating lipids in both the
      cytosolic and membranous fractions. Bilirubin-induced inhibition of
      phosphorylation of endogenous proteins, in both fractions, was noted in the
      presence of calcium and the activating lipids, but not in the absence of the
      activators. This inhibition may play a role in the pathogenesis of bilirubin
      toxicity.

PMID- 8143357
TI  - Lipoprotein composition in the insulin-deficient non-acidotic phase of type I
      diabetic patients and early evolution after the start of insulin therapy.
AB  - Lipoproteins, including intermediate density lipoproteins and lipoprotein(a), and
      apolipoproteins A-I, B, C-II, C-III and E, were studied in 13 newly-diagnosed
      type I diabetic patients with severe insulinopenia without dehydration or
      acidosis. At baseline, the main finding was a significant increase in serum
      triglycerides due to raised triglyceride concentrations in all lipoproteins,
      particularly triglyceride-rich lipoproteins. Cholesterol concentrations were
      slightly increased in lipoproteins and led to a significant increase in serum
      cholesterol. Two days after the start of insulin therapy, lipoprotein profiles
      had normalized except for the LDL triglyceride contents, which remained
      significantly increased on the fifth day of treatment. No significant
      modifications were observed in lipoprotein(a), apolipoproteins A-I and E
      concentrations throughout the study. However, serum apolipoproteins B, C-II and C
      III were increased at baseline and fell to normal levels 2 days after the start
      of insulin therapy. On the other hand, apolipoprotein C-II/C-III ratios in high
      and very low density lipoprotein, showed no significant differences at baseline
      compared with controls, suggesting that an apolipoprotein C-II deficiency or
      apolipoproteins Cs imbalance can be ruled out. In conclusion, significant
      lipoprotein abnormalities were observed in the insulin-deficient state of type I
      diabetes mellitus; insulin therapy normalizes the lipoprotein profile in two
      days, except for low density lipoprotein triglyceride contents which remain
      increased at the fifth day.

PMID- 8143358
TI  - Lipoprotein(a) serum concentration in familial combined hyperlipidemia.
AB  - The lipoprotein(a) (Lp(a) concentrations in serum were measured by an ELISA
      technique in 53 subjects affected by familial combined hyperlipidemia (FCHL) and
      in 347 healthy individuals. Lp(a) geometric means did not differ significantly
      between the two groups despite the different distributions. In hyperlipidemic
      subjects, the distribution was markedly shifted to the right (median 17 mg/dl)
      while in controls it was highly skewed to the left (median = 11 mg/dl). In FCHL,
      Lp(a) serum levels did not differ between patients with or without coronary heart
      disease (CHD). It was concluded that, differently from familial
      hypercholesterolemia (FH), in FCHL Lp(a) may not be elevated in comparison with
      an adequate control population.

PMID- 8143359
TI  - Effect of bone resorbing factors on u-PA and its specific receptor in
      osteosarcoma cell line.
AB  - This study investigated the effect of bone resorbing factors on the pericellular
      fibrinolytic system of osteosarcoma NY cells. Parathyroid hormone (PTH),
      prostaglandin E2, (PGE2) or tumor necrosis factor alpha (TNF-alpha) enhanced the
      secretion of urokinase-type plasminogen activator (u-PA) antigen and suppressed
      the secretion of plasminogen activator inhibitor-1 (PAI-1) antigen to the
      conditioned medium. The former two factors also increased u-PA antigen in the
      cell surface. Transforming growth factor beta (TGF-beta) enhanced u-PA antigen,
      but its activity was suppressed due to the increased secretion of PAI-1. The
      binding assay of [125I]DFP-u-PA to NY cells revealed the presence of a single
      class of binding sites with a Kd of 5.51 nM and Bmax of 0.92 x 10(5) binding
      sites/cell. PTH or PGE2 increased Bmax 1.4-fold and enhanced the u-PA receptor (u
      PAR) mRNA level 1.4-fold or 2.4-fold, respectively. However, TGF-beta did not
      alter either the Kd or u-PAR mRNA level. Thus, pericellular fibrinolytic activity
      by u-PA/u-PAR and PAI-1 is modulated by bone resorbing factors.

PMID- 8143360
TI  - Extremely high HDL levels in a patient with multiple symmetric lipomatosis.
AB  - An extreme form of hyperalphalipoproteinemia was studied in a patient affected by
      multiple symmetric lipomatosis (MSL); four relatives and three MSL controls were
      also evaluated. Plasma lipids and apolipoproteins were measured and overall
      lipoprotein profile was assessed by density gradient ultracentrifugation. The
      patient showed a plasma HDL-cholesterol of 138 mg/dl and an apo A-I of 218 mg/dl;
      moreover significantly high HDL levels were found in two unaffected relatives.
      The hypobetalipoproteinemia trait was also found both in the patient and in one
      of his daughters. We suggest that some pre-existing conditions may enhance
      lipoprotein metabolism alterations in this lipid storage disease.

PMID- 8143361
TI  - An enzymatic assay of inorganic phosphate in serum using nucleoside phosphorylase
      and xanthine oxidase.
AB  - We have developed a new enzymatic assay for the determination of inorganic
      phosphate (Pi) in serum, using nucleoside phosphorylase (NP) and xanthine oxidase
      (XOD). Pi and inosine react to form hypoxanthine and ribose-1-phosphate. The
      hypoxanthine is oxidized to xanthine, which is further oxidized to uric acid. In
      these two reactions 2,6-dichlorophenol-indophenol (DCIP) is reduced to a
      colourless compound and the decrease in colour is measured spectrophotometrically
      at 600 nm. The assay is automated with an RA-XT analyser. The precision of the
      automated assay is acceptable (C.V. < 3.5%) and results are accurate and linear
      across a range of values from 0.2-2.5 mmol/l. The assay correlates well with
      molybdate methods carried out on SMAC III and RA-XT analysers (r values 0.99 and
      0.98, respectively), and seems to be less prone to non-specific sample
      interference than the usual RA-XT method. The enzymatic assay described seems to
      be suitable for the routine determination of serum Pi.

PMID- 8143362
TI  - Free thyroxine measured in undiluted serum by dialysis and ultrafiltration:
      effects of non-thyroidal illness, and an acute load of salicylate or heparin.
AB  - In vitro dilution of serum during processing of a free T4 assay explains to some
      extent the divergent results obtained in non-thyroidal illness. If serum from
      such patients contains low affinity T4 protein binding inhibitors, as has been
      suggested, in vitro dilution will result in spuriously reduced serum free T4
      measurements. If these inhibitors cross the dialysis membrane in an equilibrium
      dialysis assay, their inhibitory effect will be weakened, and in vitro free T4
      levels will decrease, even in undiluted serum. In contrast, ultrafiltration
      methods on undiluted serum seem accurate. We have compared a new, commercially
      available dialysis technique with an in-house ultrafiltration method for free T4
      measurements in undiluted serum. Control subjects (n = 41) had 14% higher free T4
      (P < 0.02) by ultrafiltration. Non-thyroidally ill patients not receiving
      glucocorticoids or dopamine (n = 54) had unaltered free T4 levels, 28.4 +/- 10.3
      pmol/l (dialysis) and 31.0 +/- 10.3 pmol/l (ultrafiltration). Dopamine infusion
      in somatic ill patients (n = 11) resulted in reduced free T4 in both assays but
      only significantly for dialysis, and subjects with familial dysalbuminemic
      hyperthyroxinemia (n = 8) had unaltered free T4 levels in both assays. Salicylate
      (1.5 g) given orally 09:00 h. (n = 5) resulted within 30 min, in increased (P <
      0.01) free T4 as measured by both techniques, although more pronounced and
      sustained as measured by ultrafiltration. Serum TSH decreased concomitantly (P <
      0.01). These findings were confirmed when salicylate was administered at 13:00 h.
      (n = 8). The dialysis procedure resulted in a decrease in serum salicylate of 14%
      (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143363
TI  - Total pancreatic and salivary serum iso-amylase activities in alcohol misusers in
      relapse and remission and in alcoholic liver disease.
AB  - By means of immunoinhibition by specific salivary monoclonal antibodies in
      combination with a chromogenic substrate, assays of serum amylase were performed
      in control subjects, in chronic alcohol misusers in relapse or remission and in
      patients with alcoholic liver disease (ALD). There was a selective increase in
      the salivary isoenzyme in the ALD group. There were no significant changes in
      either of the alcohol misusing groups, compared with control subjects. It is
      suggested that the increase in salivary iso-amylase observed in patients with ALD
      is related to the previously reported functional and histological abnormalities
      in the parotid glands of this group of patients. It is also suggested that assay
      of pancreatic iso-amylase may be more discriminatory than total amylase levels in
      detecting pancreatic disease in patients with alcoholic cirrhosis.

PMID- 8143364
TI  - Prenatal screening for Down's syndrome and human chorionic gonadotropin isoforms.

PMID- 8143365
TI  - Stability of human plasma atrial natriuretic peptide during storage at -80
      degrees C.

PMID- 8143366
TI  - Pedigree of serum extracellular-superoxide dismutase level.

PMID- 8143367
TI  - The molecular mass and concentrations of protein 1 or Clara cell protein in
      biological fluids: a reappraisal.

PMID- 8143368
TI  - Immunonephelometric/turbidimetric apolipoprotein B assays for the clinical
      laboratory.
AB  - Because apolipoproteins are a part of complex macromolecular particles,
      modifications to the assay system may substantially alter results of
      immunological measurement. Accuracy as analytical recovery cannot be effectively
      determined by adding exogenous apolipoproteins because antibody access differs
      from access to endogenous apolipoproteins. Clinical studies are essential for
      determining accuracy in terms of clinical effectiveness. Since different kit
      methods use different reagent systems, the purpose of the present study was to
      compare total cholesterol and LDL cholesterol as markers for coronary artery
      disease with apo B by automated rate nephelometric, end-point nephelometric and
      turbidimetric kit methods. The subjects were age matched, male patients with and
      without angiographically documented coronary artery disease. High correlation
      coefficients (0.95-0.96) between the assays for both the normal and disease
      groups indicate that the methods are providing similar information: apo B was a
      better marker for coronary artery disease (CAD) than total or LDL cholesterol on
      the basis of univariate, multivariate and Bayesian statistics and correlated best
      with non-HDL cholesterol. Apo B along with HDLC could explain the variability
      between the CAD and normal groups without LDLC, total C, or triglycerides.

PMID- 8143369
TI  - Effect of tamoxifen on serum cholesterol and lipoproteins during chemohormonal
      therapy.
AB  - The effect of tamoxifen on serum cholesterol, high density lipoprotein
      cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL
      cholesterol) and the ratio of LDL-cholesterol to HDL-cholesterol (LDL-C/HDL-C)
      was investigated in breast cancer patients undergoing therapy for advanced
      disease. Longitudinal studies in 24 patients treated with tamoxifen (10 mg, twice
      daily) indicated average decreases in total serum cholesterol (17%) and LDL
      cholesterol (27%), whereas the effect of tamoxifen on HDL-cholesterol varied with
      the individual patient. There was a significant decrease in the LDL-C/HDL-C ratio
      (33%) consistent with a decreased risk for coronary artery disease. This
      beneficial influence of tamoxifen on risk factors associated with cardiovascular
      disease was evident in both premenopausal and postmenopausal patients whether
      tamoxifen was administered alone or in combination with cytotoxic chemotherapy.

PMID- 8143371
TI  - Lactate dehydrogenase isoenzyme patterns in blood cells from histiocytosis X
      children.
AB  - To find a clinical assay for histiocytosis X (HX) diagnosis, measurements were
      made of both activity and isoenzyme distribution of lactate dehydrogenase (LDH;
      EC 1.1.1.27) from the blood cells of 6 acute phase and 9 remission patients. A
      significant increase in the LDH activity measured in the monocytes and
      lymphocytes isolated from the blood of the acute phase patients was found. The
      increased activity was due to an enhancement of the normal pattern of LDH
      isoenzymes in these cells and not to a change in isoenzyme distribution. No
      increase was found in monocyte LDH isoenzymes from the patients in remission.

PMID- 8143370
TI  - Cholesterol in remnant-like lipoproteins in human serum using monoclonal anti apo
      B-100 and anti apo A-I immunoaffinity mixed gels.
AB  - We have developed a simple, rapid assay method for apo E-rich lipoproteins (d <
      1.006 g/ml), using an immunoaffinity gel mixture of anti apo B-100 and apo A-I
      antibodies coupled to Sepharose 4B. The immunoaffinity mixed gels adsorb normal
      lipoproteins containing apo A-I quantitatively as well as most lipoproteins
      containing apo B-100. Unbound lipoproteins are quantified by assay of
      cholesterol. Characterization of the unbound lipoproteins of d < 1.006 g/ml (J
      Lipid Res 1992; 33: 369-380) has shown that they represent chylomicron and VLDL
      remnant-like particles (RLP). RLP-Cholesterol(C) levels in plasma have been
      determined in 363 male and female normolipidemic subjects (mean +/- S.D.: 72 +/-
      16 mg/l) and have been found to be higher in patients with coronary heart disease
      and familial dysbetalipoproteinemia. Triglyceride-rich lipoproteins may well
      contain both atherogenic and non-atherogenic particles that can be separated by
      this simple immunoadsorption assay.

PMID- 8143372
TI  - Metabolites of dietary (soya) isoflavones in human urine.
AB  - This study was undertaken to better understand the metabolic fate of dietary
      isoflavones in humans. Twelve volunteers were challenged with soya flour and
      urinary diphenol levels were then determined by gas chromatography (GC) and gas
      chromatography-mass spectrometry (GC-MS). The presence of previously described
      urinary diphenols was confirmed, i.e. the isoflavones, daidzein and genistein;
      the isoflavonoid metabolites, equol, dihydrodaidzein (Int-O-D), O-desmethyl
      angolensin (O-Dma); the lignan, enterolactone. Diphenols detected for the first
      time were the isoflavone, glycitein and five novel isoflavonoid metabolites which
      are tentatively identified as 6'-hydroxy-O-desmethylangolensin (6' OH-O-Dma),
      dihydrogenistein (Int-O-G), dehydro-O-desmethylangolensin (dehydro-O-Dma) and two
      isomers of tetrahydrodaidzein. Urinary excretion rates of the three isoflavones
      (daidzein, genistein, glycitein) over a 3-day period following soya challenge
      showed moderate variation (4x, 6x and 12x, respectively) between the 12
      individuals suggesting some individual variabilities in ability to deconjugate
      and to absorb dietary isoflavones. However, urinary excretion rates of each of
      three major isoflavonoid metabolites (equol, O-Dma, 6' OH-O-Dma) showed more
      marked variation (922x, 17x, 15x, respectively); while some of this variability
      may reflect varying individual ability to ferment dietary isoflavones per se, an
      inverse relationship was found between urinary levels of equol and both O-Dma and
      6' OH-O-Dma suggesting individual variability in the preferred metabolic pathways
      of dietary isoflavones.

PMID- 8143374
TI  - Laboratory techniques used in the diagnosis of chancroid, granuloma inguinale,
      and lymphogranuloma venereum.
AB  - The preceding discussion summarized the historical, modern, and evolving
      laboratory techniques for the diagnosis of chancroid, GI, and LGV. The correct
      diagnosis of these sexually transmitted diseases, which are uncommon in the
      United States and Europe but often endemic in Africa, Asia, and South American,
      can usually be made if appropriately selected laboratory techniques are used to
      confirm the presumptive clinical impression.

PMID- 8143373
TI  - High adenosine content in human uterine smooth muscle compared with striated
      skeletal muscle.
AB  - We determined the concentrations of adenosine and some of its catabolic products
      in biopsy specimens from predetermined loci of human myometrium under different
      functional conditions to compare uterine muscle with rectus abdominis muscle from
      the same individuals. In order to achieve a good resolution in the separation of
      nucleosides and purine bases, a preseparation procedure was developed prior to
      analysis of these compounds on high performance liquid chromatography. Adenosine
      occurred in a nearly 70-fold higher concentration in smooth uterine muscle in
      comparison with striated skeletal muscle. Similarly, myometrial inosine and
      hypoxanthine were 7- and 2.4-times in excess over the rectus muscle, whereas
      xanthine was scarcely and rather evenly represented in the two types of muscles.
      The uterine content of adenosine and inosine was distinctly higher in pregnant
      women compared to non-pregnant ones. A regional difference existed for adenosine,
      with 3.3 times higher concentration in fundus uteri compared to the isthmic part.
      A reverse pattern was observed for hypoxanthine and inosine, being 2-3 times more
      frequent in the isthmic part. The orthophosphate concentration was not
      stoichiometrically related to the adenosine concentration in a simple way, being
      2-3 times lower in uterine muscle compared to the skeletal muscle. A significant
      correlation existed between uterine contents of AMP and adenosine and similarly,
      significant inverse correlations were apparent between uterine ATP and ADP
      contents and energy charge on one hand and adenosine content on the other.

PMID- 8143375
TI  - Laboratory evaluation of the child with recalcitrant eczema.
AB  - This article discusses many of the more common diagnoses that should be
      considered when managing a child with nonresponsive excema. Some of these
      possible diagnoses are infectious and parasitic disorders, psoriasis, heritable
      disorders, Langerhans cell histiocytosis, and syndromes with altered immunity and
      eczematous skin changes. This overview of diagnostic and laboratory evaluations
      of the child with eczema who fails standard therapy is presented as a useful
      guide in evaluating these patients.

PMID- 8143376
TI  - Laboratory tests for epidermolysis bullosa.
AB  - Determination of the correct diagnosis and subclassification of inherited and
      acquired forms of epidermolysis bullosa (EB) can be exceedingly challenging
      because the clinical morphologic findings and routine histology are frequently
      nonspecific. The most precise means of diagnosing inherited EB involves the
      assessment of a combination of ultrastructural and antigenic features by
      transmission electron microscopy, immunofluorescence antigenic mapping, and EB
      related monoclonal antibody studies. Acquired EB can usually be diagnosed by
      split skin indirect or direct immunofluorescence. When necessary, immunoelectron
      microscopy, immunoprecipitation, and immunoblot can be used.

PMID- 8143377
TI  - Update on immunofluorescent testing in bullous diseases and lupus erythematosus.
AB  - One of the earliest methods for investigating the immunologic basis of disease
      was the use of immunofluorescence (IF) on skin biopsy specimens and serum. IF can
      be used to detect immunoglobulins, complement components, and fibrin. In some
      diseases, the IF findings are disease specific and diagnostic, especially in
      certain bullous diseases. The use of IF testing has increased with the recent
      development of the salt split skin technique. The newer IF findings in some well
      established immunodermatologic diseases and several recently described diseases
      are discussed. A brief description of the techniques involved in direct and
      indirect IF is also presented.

PMID- 8143378
TI  - Diagnostic electron microscopy in dermatology.
AB  - The diagnostic use of electron microscopy has greatly diminished since the advent
      of sophisticated immunohistochemistry, which is faster and cheaper. In several
      skin diseases, however, electron microscopy is still the test of choice. This
      article presents a discussion of some of the diseases diagnosed through the use
      of electron microscopy.

PMID- 8143379
TI  - Serologic tests for connective tissue diseases and the primary vasculitides.
AB  - This article provides a brief historical perspective on the development of tests
      for antiphospholipid antibodies, antinuclear antibodies, myositis-specific
      antibodies, and antineutrophil cytoplasmic antibodies in the clinical laboratory.
      Tests presently available in most clinical laboratories that are used in the
      diagnosis and treatment of the connective tissue diseases and the vasculitides
      are discussed. Mention is made of antibodies under study in the research
      laboratories.

PMID- 8143380
TI  - Vascular studies of the legs for venous or arterial disease.
AB  - The basis of in-office evaluation of leg vascular disease involves Doppler
      ultrasound to estimate flow in arteries and veins. Arterial evaluation localizes
      sites of obstruction by segmental pressures obtained by Doppler signal assessment
      using pressure cuffs. Ankle compared with brachial arterial pressure is the most
      rapid screening test. Plethysmography permits more automated and sensitive
      analysis of pressure waveforms. Venous evaluation identifies sources of increased
      pressure transmitted by incompetent valves to surface veins causing varicosities
      and telangiectases. Doppler ultrasound permits sites of reverse flow (incompetent
      valves) to be localized, whereas plethysmography enables physiologic consequences
      of incompetent valves to be analyzed. Plethysmography with pressure cuff
      placement localizes deep system disease versus superficial disease, and rules out
      deep malfunction. When in-office diagnostic tests are equivocal, duplex
      ultrasound or more invasive tests should be considered.

PMID- 8143381
TI  - Laboratory tests for Lyme disease.
AB  - The laboratory diagnosis of Lyme disease has been problematic because of the lack
      of sufficient sensitivity and specificity of the many tests used as well as the
      lack of interlaboratory standardization in the performance of these tests.
      Although helpful, the laboratory tests can only serve to support the clinical
      findings in making the diagnosis of active Lyme disease, the exception being a
      positive culture of Borrelia Burgdorferi.

PMID- 8143382
TI  - Treatment of cutaneous lesions in patients with lupus erythematosus.
AB  - After proper classification of cutaneous lesions in LE patients and extensive
      evaluation, we can begin to approach effective therapy. Patients with CLE (DLE or
      SCLE) generally have a favorable prognosis and can be managed with safe yet
      effective therapy. Sunscreens are the most important topical therapy.
      Intralesional corticosteroids are an effective local adjunctive therapy, useful
      in bringing lesions under control. Systemic therapy with antimalarials, either
      used singly or in combination, is usually effective. When "standard" therapy
      fails, azathioprine, retinoids, or occasionally dapsone may be effective.

PMID- 8143383
TI  - Diagnostic tests for Rocky Mountain spotted fever and other rickettsial diseases.
AB  - Rickettsial diseases continue to confound physicians because of their usually
      sporadic occurrence and nonspecific clinical presentation. In past years,
      diagnosis was confirmed only during convalescence; however, newer, more widely
      available methods, such as antigen detection and improved in vitro cultivation,
      have enabled a diagnosis at a time when therapeutic decisions are made. Molecular
      nucleic acid-based techniques have also expanded the spectrum of etiologic agents
      and illnesses caused by rickettsiae.

PMID- 8143384
TI  - Laboratory tests for the diagnosis and evaluation of leishmaniasis.
AB  - This article presents various methods used in the diagnosis and evaluation of
      leishmaniasis. Because therapy is prolonged and potentially toxic, confirmation
      of the diagnosis is desirable. This is especially true in areas where disease is
      not endemic or where clinical presentation is not typical.

PMID- 8143385
TI  - Tests for detecting herpes simplex virus and varicella-zoster virus infections.
AB  - Several laboratory diagnostic methods are available for the diagnosis,
      differentiation, and subtyping of HSV and VZV infections. In the office or at the
      bedside of a hospitalized patient, a positive Tzanck smear preparation is an
      inexpensive, rapid, and morphologic technique for confirming a suspected
      diagnosis of a herpesvirus infection. An expedient, slightly more expensive,
      reliable technique for establishing a HSV infection, yet not able to
      differentiate the subtype of that infection, is a recently marketed monoclonal
      antibody-based filtration type enzyme immunoassay (Kodak SureCell Herpes Test
      Kit). Serologic tests traditionally do not have a major role in the diagnosis of
      HSV infection; yet, new type-specific methods using Western blot assays may be
      useful for confirming the presence of unrecognized, subclinical HSV2 infections
      that are presently being underdiagnosed by current procedures. The gold standard
      for establishing the diagnosis of HSV infection has been the viral tissue
      culture. The fluorescent antibody to membrane antigen test and viral tissue
      culture have been the principal methods for diagnosing VZV infection.
      Immunomorphologic techniques have been useful adjuvant methods for both the
      diagnosis and the differentiation of HSV and VZV infections. Molecular virology
      techniques (particularly those using PCR) are likely to become the diagnostic
      methods of choice for both HSV infection and VZV infection once these tests
      become commercially available.

PMID- 8143386
TI  - Laboratory testing in patients with morbilliform viral eruptions.
AB  - The explosion of immunologic testing capabilities over the past 20 years has
      enabled clinicians to accurately diagnose many conditions that previously were
      very difficult to identify solely on a clinical basis. Among these disorders are
      the viral exanthems. Infections with some of these viruses are of relatively
      little import (erythema infectiosum), whereas others have more significant
      consequences (HIV, cytomegalovirus). Clinical suspicions may be pursued more
      fully now, sometimes even in an office setting.

PMID- 8143387
TI  - Obtaining a skin biopsy specimen and interpreting the results.
AB  - Skin biopsy specimens are interpreted by general pathologists and dermatologists,
      as well as by devoted dermatopathologists. Pitfalls of obtaining the biopsy
      specimen, grossing the specimen, evaluating the sections, and reporting the
      results are discussed on an advanced level. Controversial economic issues and
      government regulations are tackled, with respect to how they affect the final
      result. Last, several stereotypes of prototypical dermatologic surgeons and
      dermatopathologists are used to illustrate how practice patterns affect the
      accuracy of subjective skin biopsy specimen reports.

PMID- 8143388
TI  - Testing for syphilis.
AB  - Syphilis remains an important public health problem of growing proportions
      despite effective means of prevention and therapy. Clinical staging is difficult.
      The diagnosis is complicated by the lack of an easy culture method. History,
      clinical findings, and the detection of spirochetes in tissue serve as the basis
      for diagnosis. Simple nontreponemal tests are available for screening, and more
      difficult treponemal tests are used for confirmation. False-positive test results
      are more common with the reaginic tests but are also seen with the specific
      antitreponemal tests. The diagnosis of central nervous system syphilis is
      imprecise and is of particular importance in HIV-positive individuals. HIV
      infection has complicated the diagnosis of syphilis with serologic testing,
      although the current tests are generally adequate. Follow-up testing after
      treatment is used to confirm a therapeutic response. New diagnostic tests,
      including monoclonal antibody staining and the polymerase chain reaction, may
      ultimately assist in the diagnosis of this ancient disease that still has major
      health implications in the modern world.

PMID- 8143389
TI  - The Pinocchio factor.

PMID- 8143390
TI  - Centers for education and research in therapeutics.

PMID- 8143392
TI  - Pharmacokinetics and pharmacodynamics of (+)-threo-methylphenidate enantiomer in
      patients with hypersomnia.
AB  - The pharmacokinetics of (+)-methylphenidate after oral administration of 20 mg
      racemic methylphenidate hydrochloride and the relationship between clinical
      effects of plasma (+)-methylphenidate concentration were investigated in 15
      patients with hypersomnia and four healthy volunteers. The elimination half-life
      of (+)-methylphenidate in patients was within the range of 2.6 to 3 hours, and
      the time to reach the peak concentration ranged from 1 to 3 hours. The values of
      half-life and time to reach the peak concentration in the patients were almost
      the same as the values in healthy subjects. The plasma (+)-methylphenidate
      concentration profiles after repeated administration of racemic methylphenidate
      were similar to those after single administration. No correlation was observed
      between the plasma (+)-methylphenidate concentration and the subjective
      sleepiness as measured by Stanford Sleepiness Scale. On the other hand, a
      significant correlation was found between the sleep latency as measured by the
      multiple sleep latency test and the plasma concentrations of (+)-methylphenidate
      (r = 0.850). The time course of the sleep latency after repeated administration
      was similar to that after single administration. The sleep latency of more than
      10 minutes was achieved by maintaining the plasma (+)-methylphenidate
      concentrations above 3 ng/ml.

PMID- 8143391
TI  - Variable disposition kinetics and electrocardiographic effects of flecainide
      during repeated dosing in humans: contribution of genetic factors, dose-dependent
      clearance, and interaction with amiodarone.
AB  - We studied the influence of cytochrome P450 2D6 (CYP2D6) on the steady-state
      disposition kinetics and the electrocardiographic effects of flecainide at two
      doses and during combination with amiodarone. Seven extensive and five poor
      metabolizers of dextromethorphan were studied during a three-period crossover
      study. All subjects received 50 mg flecainide every 12 hours, alone or together
      with 200 mg amiodarone every 12 hours, and 100 mg flecainide every 12 hours for 5
      days. Mean steady-state plasma concentration of flecainide and QRS change from
      predrug value did not differ significantly among extensive and poor metabolizer
      subjects during each study period. Except for a shortened elimination half-life
      and nonlinear kinetics in extensive metabolizer subjects, phenotype had no
      significant influence on flecainide pharmacokinetics. Combination with amiodarone
      resulted in an increase in mean flecainide plasma concentration and effect in
      subjects with both phenotypes. Our findings indicate that CYP2D6 phenotype
      predicts flecainide nonlinear kinetics and flecainide half-life but has no
      influence on electrocardiographic effects during repeated administration of
      flecainide or on the extent of the amiodarone-flecainide interaction.

PMID- 8143393
TI  - Choline pharmacokinetics during intermittent intravenous choline infusion in
      human subjects.
AB  - A study of choline pharmacokinetics was undertaken in four patients receiving
      long-term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol
      choline chloride were intravenously infused over a 12-hour period in each
      subject. The choline concentration was determined in plasma at baseline, 1/4, 1,
      3, 6, and 12 hours, and 3 and 12 hours after the infusion ended, and in daily 24
      hour urine collections. Analysis of variance showed the data fit a two
      compartment model in which elimination from the central compartment was saturable
      significantly better than a one-compartment model in all four subjects (p < 10(
      8) in all cases), and significantly better than a nonsaturating model in three of
      the four subjects (p = 1.0 x 10(-9), 7.5 x 10(-6), 9.4 x 10(-11), respectively).
      The model allowed estimates of the rate constant for choline elimination at
      ambient levels, first-order rate constants for transfer between central and
      peripheral compartments, the dissociation constant for the saturable elimination
      process, the apparent volume of distribution in the central compartment, the
      steady-state volume of distribution, and the quantities of choline in the central
      compartment and in the readily exchangeable pool.

PMID- 8143394
TI  - Comparative tear concentrations over time of ofloxacin and tobramycin in human
      eyes.
AB  - The pharmacokinetic profiles of 0.3% ofloxacin and 0.3% tobramycin ophthalmic
      solutions after multiple administrations in the eyes of 160 healthy volunteers
      were evaluated. In human tears, ofloxacin and tobramycin were found to have
      terminal half-lives of 226 and 154 minutes, respectively. The mean residence time
      in the ocular tear fluid was 326 minutes for ofloxacin and 106 minutes for
      tobramycin. The mean duration of time that ofloxacin remained above the MIC90
      value for five bacterial species evaluated was 605 minutes, compared with 251
      minutes for tobramycin. The mean area under the inhibitory curve for the five
      bacterial species evaluated was greater for ofloxacin (2224) compared with
      tobramycin (1549). The duration of time above the MIC90 for ofloxacin was longer
      compared with tobramycin for gram-positive isolates. Overall, the pharmacokinetic
      and pharmacodynamic profiles of ofloxacin were superior to those of tobramycin
      for most parameters studied.

PMID- 8143395
TI  - Caffeine metabolism in a healthy Spanish population: N-acetylator phenotype and
      oxidation pathways.
AB  - We studied the oxidative and N-acetylator caffeine metabolic profile in 107
      healthy Spanish volunteers. Smokers had significantly higher N-1- and N-3
      demethylations activities than nonsmokers (p = 0.03 and p = 0.02, respectively),
      and the three caffeine demethylations indexes were strongly correlated with each
      other (r > 0.7; p < 0.001). Our in vivo studies suggest that CYP1A2 is involved,
      at least in part, in the primary N-demethylations of caffeine. A non-normal and
      possibly bimodal distribution was detected in the xanthine oxidase activity (p =
      0.04), with about 4% of subjects deficient of this metabolic activity. The
      population exhibited a trimodal distribution of acetylator phenotype determined
      by use of the 5-acetylamino-6-amino-3-methyluracil/1-methylxanthine ratio
      (normality test; p = 0.004). Seventy subjects (65.4%) were phenotyped as slow
      acetylators. The mutated gene frequency was 0.81, which is similar to other white
      populations.

PMID- 8143396
TI  - Concomitant etodolac affects neither the unbound clearance nor the pharmacologic
      effect of warfarin.
AB  - Potential interactions between the nonsteroidal anti-inflammatory etodolac and
      the anticoagulant warfarin were studied in 18 healthy subjects by use of a
      randomized, three-period crossover design. Each treatment lasted 2 1/2 days and
      consisted of warfarin, etodolac, or both drugs. Prothrombin time was determined
      daily during each warfarin period to measure pharmacologic effect. Total serum
      concentration and unbound fraction of both drugs were determined over the dose
      interval after the last dose of the study drug(s). Concomitant etodolac did not
      affect the prothrombin time response or the unbound clearance of warfarin. During
      concomitant etodolac administration, the median peak concentration of total
      warfarin was significantly decreased by 19% (p = 0.005), median total clearance
      was significantly increased by 13% (p = 0.0123), and the unbound fraction tended
      to increase (median unbound fraction of warfarin, 1.245% with etodolac and 1.045%
      without etodolac; p = 0.0979; not statistically significant). These observations
      suggest a small displacement of warfarin from serum protein by etodolac or a
      metabolite of etodolac. No etodolac pharmacokinetic parameter was significantly
      affected by concomitant warfarin administration. Thus etodolac does not appear to
      alter the unbound clearance of warfarin or augment its pharmacologic effect.
      Nevertheless, it is prudent that clinical monitoring be done for individuals
      taking these two compounds concomitantly.

PMID- 8143397
TI  - The concentration-effect relationship of quinine-induced hearing impairment.
AB  - Quinine-induced reversible hearing impairment at the frequencies of 1000 and 2000
      Hz was investigated in healthy volunteers to analyze the plasma concentration
      effect relationship of the drug. Six subjects were given two identical oral doses
      of quinine and a constant rate infusion of quinine over 6 hours (15 mg.kg-1) on
      three separate occasions. A simple pharmacodynamic model, E = k.C gamma (in which
      E is effect, k is a proportionality constant, C is drug concentration, and the
      exponent gamma is a fitting parameter), was found to describe well the
      relationship between hearing impairment and quinine concentrations in a
      hypothetical effect compartment. No statistical differences were found in the
      estimated parameters when the three dosings were compared, indicating that
      quinine-induced hearing impairment is independent of route of administration. The
      first-order rate constant (keo), linking plasma concentrations to the
      concentrations in the effect compartment, was (mean +/- SD) 0.71 +/- 0.19 and
      0.99 +/- 0.37 hr-1 for 1000 and 2000 Hz, respectively. The corresponding values
      of k were 0.15 +/- 0.10 and 0.12 +/- 0.19 and the values of gamma were 2.13 +/-
      0.57 and 3.44 +/- 1.04 for 1000 and 2000 Hz, respectively. Effect was also
      analyzed by semiparametric pharmacodynamic modeling, which gave results
      comparable to those obtained with the link model. We conclude that a simple power
      function is a reliable pharmacodynamic model for describing quinine-induced
      hearing impairment in healthy subjects.

PMID- 8143398
TI  - Short-term effects of smoking marijuana on balance in patients with multiple
      sclerosis and normal volunteers.
AB  - A double-blind randomized placebo-controlled study of inhaled marijuana smoke on
      postural responses was performed in 10 adult patients with spastic multiple
      sclerosis (MS) and 10 normal volunteers matched as closely as possible for age,
      sex, and weight. A computer-controlled dynamic posturographic platform with a
      video line scan camera measured shoulder displacement in response to pseudorandom
      platform movements. Premarijuana smoking patient tracking was inferior to that of
      the normal volunteers as indicated by the higher noise variance of the former.
      Smoking one marijuana cigarette containing 1.54% delta 9-tetrahydrocannabinol
      increased postural tracking error in both the patients and normal control
      subjects with both eyes open and closed; this untoward effect was greatest for
      the patients. The tracking error was also accompanied by a decrease in response
      speed for the patients with their eyes closed. Marijuana smoking further impairs
      posture and balance in patients with spastic MS.

PMID- 8143399
TI  - Extended-release felodipine in patients with mild to moderate hypertension.
      Felodipine ER Dose-Response Study Group.
AB  - Two hundred eighty-six patients with mild to moderate hypertension who had
      untreated diastolic blood pressure while seated of 95 to 115 mm Hg were
      randomized to receive placebo or once-daily doses of 2.5, 5, or 10 mg of the
      dihydropyridine calcium channel blocker felodipine extended release (ER). Blood
      pressure was measured 24 hours after dosing (at trough). Mean reductions in
      diastolic blood pressure after 8 weeks of double-blind treatment were
      significantly greater in each of the ER felodipine treatment groups (2.5, 5, and
      10 mg ER felodipine: -7.8, -9.5, and -11.3 mm Hg, respectively) than in the
      placebo group (-5.3 mm Hg). The effect was dose dependent for both diastolic and
      systolic blood pressure. Moreover, much of the peak antihypertensive effect was
      still present at trough, confirming the 24-hour efficacy of the drug. Felodipine
      was well tolerated.

PMID- 8143400
TI  - A concurrent audit of high digoxin plasma levels.
AB  - A concurrent audit was made of 92 patients with plasma or serum digoxin levels of
      3.0 ng/ml or more. Evidence of digoxin toxicity was present in 44 of these
      patients, and premature blood sampling accounted for the high levels in 30
      nontoxic patients. Another 14 patients tolerated high digoxin levels without
      apparent adverse effects. Impaired renal function appeared to increase the risk
      of digoxin toxicity, even though digoxin levels were similar in patients with and
      without toxicity. Pharmacokinetic predictions based on patient weight and
      creatinine clearance often deviated considerably from measured digoxin levels
      even when these were drawn appropriately.

PMID- 8143401
TI  - Effect of advanced age on the pharmacodynamics of doxacurium.

PMID- 8143402
TI  - Staging of lymphoma in adults.

PMID- 8143403
TI  - Expandable metal stents for tracheobronchial obstruction.
AB  - We report our experience of the use of endoscopically inserted expanding
      stainless steel stents in 18 patients over a period of 31 months. Twelve patients
      had stents inserted for malignant disease causing narrowing of the
      tracheobronchial tree, and six for airway complications following heart-lung,
      single lung or double lung transplantation. In all but one case, stents were
      satisfactorily positioned, and there were no complications related to stent
      insertion. Seven patients were alive at follow-up, three of whom had stents
      inserted for malignancy and four as a result of complications following
      transplantation.

PMID- 8143404
TI  - Hodgkin's disease of the gastrointestinal tract.
AB  - Hodgkin's disease (HD) is rarely considered in the differential diagnosis of
      gastrointestinal (GI) disorders. We report eight cases of GI HD. The patients,
      ages 16-64, all with stage IV disease of varied histologic subtypes and GI
      symptoms including pain, upper or lower GI bleeding and/or obstruction. There was
      diffuse gastric fold thickening in one case, a large submucosal mass along the
      proximal greater curvature in another case, and a large ulcerating mass along the
      lesser curvature in the third case. Two cases of jejunal disease manifested as
      either a short or long segment of luminal narrowing with prominent mucosal
      nodularity. Another case exhibited a short area of complete mucosal destruction,
      irregular cavitation and intraluminal filling defect. In one additional case
      there was diffuse jejunal nodularity. Colonic involvement (two cases) presented
      as a solitary polypoid mass in transverse colon in one patient and severe
      narrowing of the descending colon with adjacent mesenteric mass on CT in another.
      We conclude that although rare in Hodgkin's disease, GI involvement should be
      considered, particularly in patients with stage IV disease.

PMID- 8143405
TI  - Colon cancer detection: an algorithm using endoscopy and barium enema.
AB  - A review of findings on flexible sigmoidoscopy (FS), colonoscopy and selected
      double-contrast barium enema (DCBE) radiographs from a group of 66 patients with
      rectal bleeding was performed to test the value of an algorithm in the detection
      of colonic cancers and polyps. In this algorithm the FS findings would direct
      patients either to colonoscopy or to a modified DCBE which focused attention on
      the colon proximal to the sigmoid. Only patients with neoplasms diagnosed by FS,
      or by MDCBE after negative FS, would proceed to colonoscopy. The study population
      contained four cancers, 11 polyps > 5 mm and 11 polyps < or = 5 mm; FS+MDCBE
      missed four polyps, all < 5 mm. For polyps > 5 mm and cancer, FS+MDCBE had a
      sensitivity of 100%, a specificity of 82%, a negative predictive value of 1.0 and
      a positive predictive value of 0.62. Using the algorithm, 24 patients (36%) would
      have required colonoscopy. The results suggest that FS+MDCBE is a potentially
      valuable method for screening patients for colonic neoplasia.

PMID- 8143406
TI  - Enteroclysis--the influence of tube design.
AB  - The performance of three 10F enteroclysis tubes with different tip designs (E.
      Merck Ltd) was assessed using double-contrast, gravity infusion enteroclysis,
      with methylcellulose solution as negative contrast. Intubation times, screening
      times, patient tolerability and examination quality were compared. The results
      show that a streamlined tip design facilitated passage through the nose. None of
      the tubes provided consistently reliable results due to inadequate flow rates.
      The Corsafe tube transmits a higher flow rate of methylcellulose and produced
      satisfactory examinations more frequently. Mechanically assisted infusion of
      methylcellulose is recommended when using 10F enteroclysis tubes.

PMID- 8143407
TI  - Benefit of intravenous muscle relaxants during barium follow through.
AB  - The value of an intravenous (i.v.) smooth muscle relaxant during barium follow
      through (BaFT) examination has been evaluated in a prospective study of 51
      patients. Spot compression films pre- and post-relaxant were compared. Relaxant
      induced hypotonia improved image quality in 33 (64.8%) patients by facilitating
      bowel loop separation and/or graded compression. Additional diagnostic
      information was obtained in 14 (27.5%), and reporting confidence was improved in
      19 (37.3%) patients. A marked analgesic effect occurred in seven patients with
      Crohn's disease, ameliorating pain that otherwise prevented full compression.
      Intravenous relaxants are recommended when high tone makes compression difficult,
      to help separate overlying loops and where pain in Crohn's disease prevents
      adequate compression.

PMID- 8143408
TI  - Ischaemic colitis in association with sigmoid carcinoma: a report of two cases.
AB  - The association of ischaemic colitis with a distal obstructing carcinoma is
      described in two patients. When a segment of colonic ischaemia is demonstrated on
      barium enema, it is important to consider an association with a distal tumour.

PMID- 8143409
TI  - Mammographic appearances in Paget's disease of the breast.
AB  - The mammographic appearances in 17 patients with Paget's disease of the breast
      were retrospectively reviewed. Appearances were normal in only five cases.
      Microcalcification was present in 10 including one where it encircled the nipple.
      A radiologically-visible tumour was seen in nine breasts with carcinoma being
      diagnosed in a further three by the pattern of calcification alone. Multifocal
      tumours were present in four breasts but no lymphadenopathy or contralateral
      tumours were seen. Despite high quality radiography a tumour was only detected in
      71% of cases of Paget's disease and radiographers should be trained to recognize
      the condition clinically. Patients without a visible tumour may be suitable for
      radiotherapy.

PMID- 8143410
TI  - Colour Doppler studies of axillary node metastases in breast carcinoma.
AB  - Colour Doppler scans were carried out on 80 patients with breast carcinoma. Both
      the tumour and the lower axilla were scanned in all 80 patients. Seventy-five
      patients subsequently underwent axillary lymph node dissection and histological
      examination. The sensitivity of colour Doppler scanning for axillary node
      involvement was 70%, with a specificity of 98% and a positive predictive value of
      96%.

PMID- 8143411
TI  - The utility of nasal bone radiographs in nasal trauma.
AB  - A prospective study was performed to assess the value of nasal bone radiographs
      taken in the accident and emergency department. The study population consisted of
      100 consecutive patients who had nasal bone radiographs in our accident and
      emergency (A&E) department following trauma. We looked at the casualty officers',
      radiologists' and ENT surgeons' assessment of the cases. Thirty months later we
      reviewed the patients' notes to identify the number who sought medico-legal
      reports on their injury in that interval. We found sporting injuries to be the
      commonest mechanism of injury, followed closely by accidental falls. The
      remaining third was made up predominantly of cases of personal assault and road
      traffic accidents. Only two patients had a naso-pharyngeal history recorded on
      their visit to A&E. Thirty-five patients were referred to ENT out-patients, only
      24 kept their appointment. Thirty-one of the 35 ENT referrals were felt to have a
      fracture demonstrated on their radiographs. However, 19 of those discharged were
      also thought to have an X-ray-proven fracture. Thirty months later only two
      patients had requested a medico-legal report. We demonstrate that the decisions
      regarding treatment of nasal trauma are based on clinical findings and that nasal
      bone radiography has no place in the decision making process and should therefore
      be abandoned.

PMID- 8143412
TI  - Mucosal antral cysts observed within a London inner-city population.
AB  - Mucosal antral cysts(MACs) appear as dome-shaped soft-tissue opacities and have
      prevalences of between 1.6% and 8.7% on otherwise normal panoramic radiographs.
      The aim of this survey was to define the prevalence in the inner-city population
      in London. A 14% prevalence for MACs was observed in the panoramic radiographs of
      1000 consecutive patients attending King's College Hospital dental casualty
      department sited in inner London, which is higher than those reported for other
      populations. MACs were not significantly associated with the presence of signs
      and symptoms of periapical areas of bone loss. The differential diagnosis and
      management of these lesions are discussed.

PMID- 8143413
TI  - Should we have confidence in radiology papers?
AB  - This study aims to assess whether Confidence Intervals are used appropriately in
      papers published in Clinical Radiology, and compares 50 consecutive papers in
      this journal with similar samples in Radiology and the British Medical Journal
      (BMJ). The utilization or omission of Confidence Intervals and statistical
      hypothesis testing is analysed. The results are discussed using chi 2 tests and
      95% Confidence Intervals for the difference between proportions. This illustrates
      the important additional quantitative information that Confidence Intervals can
      convey, particularly when evaluating the degree of uncertainty related to a
      result from a small sample or subgroup in a study.

PMID- 8143414
TI  - Superior vena caval obstruction managed by the Gianturco Z Stent.
AB  - Twenty patients with superior vena caval obstruction (SVCO) due to malignancy
      were managed using the Gianturco Z Stent. Three patients had adjunctive
      thrombolysis. The primary clinical success was 90% (18/20 patients). Thirteen
      patients were free of SVCO to death or follow-up without re-intervention (primary
      patency = 65%). Three patients had re-intervention for recurrent symptoms, two
      successfully (secondary long-term patency = 75%). Stenting of the SVC is a
      valuable, under-used technique for the symptomatic relief of superior vena caval
      obstruction.

PMID- 8143415
TI  - Technical report: prone scanning in the CT assessment of oesophageal carcinoma.
AB  - The use of scanning in the prone position is described in the computed
      tomographic staging of oesophageal carcinoma. Examples are provided to illustrate
      how this technique may be of assistance in assessing local tumour invasion.

PMID- 8143416
TI  - Case report: ossifying fibromatosis of the breast.
AB  - We report the first described case of ossifying fibromatosis of the breast. This
      condition warrants consideration as a rare differential diagnosis of carcinoma of
      the breast and dense calcification on mammography.

PMID- 8143417
TI  - Case report: metastatic renal cell carcinoma presenting as intracerebral
      haemorrhage.
AB  - Cerebral haemorrhage is a well-established, albeit rare, complication of
      intracranial tumours. An autopsy series of 461 cerebral tumours revealed
      haemorrhage into only 2%. A case is described of intracerebral haemorrhage which
      complicated a metastatic renal cell carcinoma. There are four previous cases
      reported in the literature with this presentation, but this case differs in that
      the diagnosis was by cerebral angiography and at a site distant to the original
      haemorrhage.

PMID- 8143418
TI  - Case report: giant tuberculous cystic lymphangioma of posterior mediastinum,
      retroperitoneum and groin.
AB  - Cystic lymphangioma is a very rare condition of unknown aetiology. It is
      generally regarded as a developmental malformation in which obstruction or
      agenesis of lymphatic tissue results in lymphangiectasia secondary to lack of
      normal communication of the lymphatic system. Most lymphangiomas occur in the
      neck (75%) and axillary region (20%). Lymphangiomas may rarely occur in the
      retroperitoneum, mediastinum, mesentery, omentum, colon, pelvis, groin, spleen,
      bone and skin. We present a case of multicompartmental tuberculous lymphangioma
      extending continuously from the superior posterior mediastinum through the
      retroperitoneum to the right groin, which responded to needle aspiration and
      antituberculosis drug therapy.

PMID- 8143420
TI  - Image processing of fluoroscopic examinations.

PMID- 8143419
TI  - Case report: extravasation of lipiodol--a complication of dacryocystography.
AB  - We describe the occurrence of a significant cosmetic blemish in the cheek of a
      young girl which was caused by extravasation of 'Lipiodol' from the lacrimal
      canaliculus. Erythema and swelling lasted for several months before resolving
      completely. This complication has not been reported in the English literature
      before.

PMID- 8143421
TI  - Needle drainage of pelvic sepsis.

PMID- 8143422
TI  - Nutritional pharmacology: effects of L-arginine on host defences, response to
      trauma and tumour growth.

PMID- 8143423
TI  - Secretion of ions and pharmacological responsiveness in the mouse paw sweat
      gland.
AB  - 1. Some of the basic functional features of the mouse paw eccrine sweat gland
      were delineated to allow comparison with those of transgenic mice in the future.
      2. The mouse sweat secretory coil responds to methacholine, elaborating a K(+)
      rich (> 120 mmol/l), Na(+)-poor (< 70 mmol/l) primary fluid as does the rat paw
      sweat gland, as previously reported. The methacholine-induced sweat rate
      increases with age in parallel with the growth of the sweat gland over the first
      6 weeks of life. 3. The sweating response to cyclic AMP-elevating agents, such as
      isoprenaline or forskolin, is as much as 40% of the methacholine-induced sweat
      rate at 1 week of age, but falls to 10% by 6 weeks of age despite the fact that
      the agonist-induced tissue accumulation of cyclic AMP expressed on a per
      microgram of protein basis triples with age over the same period. 4. A marked K+
      outflux was also noted in response to methacholine and a small K+ outflux was
      seen in response to cyclic AMP-elevating agonists in superfused adult mouse
      secretory coils in vitro. 5. Since sweat secretion is usually associated with
      activation of either K+ channels or Cl- channels or both, and since the sweating
      occurred in response to cyclic AMP-elevating agonists, we speculate that the
      cyclic AMP-activated Cl- channels (the mouse version of the cystic fibrosis
      transmembrane conductance regulator) may also occur in the mouse sweat gland, but
      that the degree of their expression may be influenced by the age of the mice.

PMID- 8143424
TI  - Insulin-like growth factor-I is partially responsible for fibroblast
      proliferation induced by bronchoalveolar lavage fluid from patients with systemic
      sclerosis.
AB  - 1. Interstitial lung disease is a common complication of systemic sclerosis. The
      mechanism by which excess collagen is deposited in the lung is poorly understood,
      but is thought to involve release of mediators which activate lung fibroblasts.
      In this study we investigated and partially characterized the fibroblast
      proliferative activity of bronchoalveolar lavage fluid from 29 patients with
      systemic sclerosis, 19 with and 10 without evidence of lung disease assessed by
      thin-section computed tomography. 2. Bronchoalveolar lavage fluid from both
      groups of patients stimulated fibroblast proliferation compared with control
      subjects: systemic sclerosis with normal computed tomography, 27.7 (range 10.5
      57.9)% above control; systemic sclerosis with abnormal computed tomography, 26.7
      (range 5.0-47.8)% above control, P < 0.02 in both cases. 3. The activity was
      reduced by about one-third by neutralizing antibodies to insulin-like growth
      factor-1 but not platelet-derived growth factor. Levels of insulin-like growth
      factor-1 of bronchoalveolar fluid were increased in patients with systemic
      sclerosis [2.10 (range 1.10-3.48) ng/ml of bronchoalveolar lavage fluid] compared
      with controls [1.45 (range 1.10-2.05) ng/ml; P < 0.01]. When patients were
      subdivided into those with abnormal computed tomography [2.10 (range 1.20-3.48)
      ng/ml] and those with normal computed tomography [1.85 (range 1.10-2.90) ng/ml]
      only the values for the group with evidence of lung disease were increased
      compared with control subjects (P < 0.02). Platelet-derived growth factor could
      not be detected in bronchoalveolar lavage fluid from any group. Fractionation of
      bronchoalveolar lavage fluid demonstrated activity in several fractions
      consistent with the molecular masses of insulin-like growth factor-1 associated
      with binding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143425
TI  - Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid:
      properties, relationship to central noradrenergic neuronal activity and variation
      in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency.
AB  - 1. Dopamine beta-hydroxylase is stored and released with catecholamines by
      exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells.
      Although dopamine beta-hydroxylase enzymic activity is measurable in
      cerebrospinal fluid, such activity is unstable, and its relationship to central
      noradrenergic neuronal activity in humans is not clearly established. To explore
      the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a
      homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal
      fluid, in order to characterize the properties and stability of cerebrospinal
      fluid dopamine beta-hydroxylase, as well as its relationship to central
      noradrenergic neuronal activity and its variation in disease states such as
      hypertension, renal failure, Parkinsonism and congenital dopamine beta
      hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-hydroxylase
      immunoreactivity was present in normal human cerebrospinal fluid at a
      concentration of 31.3 +/- 1.4 ng/ml (range: 18.5-52.5 ng/ml), but at a 283 +/- 27
      fold lower concentration than that found in plasma. Cerebrospinal fluid and
      plasma dopamine beta-hydroxylase concentrations were correlated (r = 0.67, P =
      0.001). Some degree of local central nervous system control of cerebrospinal
      fluid dopamine beta-hydroxylase was suggested by incomplete correlation with
      plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal
      disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta
      hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta
      hydroxylase was not changed by the central alpha 2-agonist clonidine at a dose
      that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid
      dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid
      concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus,
      cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely
      linked either pharmacologically or biochemically to central noradrenergic
      neuronal activity. 4. Cerebrospinal fluid dopamine beta-hydroxylase was not
      changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid
      dopamine beta-hydroxylase was markedly diminished (16.3 +/- 2.9 versus 31.3 +/-
      1.4 ng/ml, P < 0.001) and rose by 58 +/- 21% (P = 0.02) after adrenal-to-caudate
      chromaffin cell autografts. In congenital dopamine beta-hydroxylase deficiency,
      lack of detectable dopamine beta-hydroxylase immunoreactivity in cerebrospinal
      fluid or plasma suggests absent enzyme (rather than a catalytically defective
      enzyme) as the origin of the disorder. 5. We conclude that cerebrospinal fluid
      dopamine beta-hydroxylase immunoreactivity, while not closely linked to central
      noradrenergic neuronal activity, is at least in part derived from the central
      nervous system, and that its measurement may be useful in both the diagnosis and
      treatment of neurological disease.

PMID- 8143426
TI  - Increase in muscle nerve sympathetic activity in humans after food intake.
AB  - 1. The influence of the intake of different nutrients on muscle nerve sympathetic
      activity was studied by use of microneurography. Muscle nerve sympathetic
      activity, heart rate, blood pressure and the insulin response were monitored for
      90 min in 39 healthy, lean, normotensive subjects (mean age 26 years) who
      received 100 g of glucose in 300 ml of water (n = 8), 50 g of fat in 250 ml of
      water (n = 8), 100 g of lean meat corresponding to 40 g of protein with 250 ml of
      water (n = 8), 300 ml of water only (n = 7) or a mixed meal (1750 kJ) (n = 8). 2.
      All types of food evoked an increase in muscle nerve sympathetic activity whereas
      water caused no change. The increase in muscle nerve sympathetic activity was
      already significant at 15-30 min and was still strongly significant at 90 min.
      The effect of glucose was significantly greater than that of fat and protein; the
      mixed meal caused an intermediate response. Blood pressure changes were minor. 3.
      It is concluded that a sustained increase in muscle nerve sympathetic activity
      occurs regularly after any type of food intake. A rise in muscle nerve
      sympathetic activity takes place in the absence of an insulin response, and
      insulin contributes to only part of the increase after ingestion of glucose or a
      mixed meal. The muscle nerve sympathetic activity response is thought to be of
      importance for the redistribution of blood to the splanchnic region after a meal.
      Lack of this response is likely to explain postprandial hypotension in autonomic
      failure.

PMID- 8143427
TI  - Forearm substrate utilization during exercise after a meal containing both fat
      and carbohydrate.
AB  - 1. Whilst the provision of exogenous carbohydrate has been shown to be beneficial
      to endurance exercise performance, little attention has been paid to the
      possibility of dietary manipulation of the availability of fat. 2. Ten normal
      subjects were studied on two occasions: after an overnight fast (postabsorptive
      state) and after a meal containing 80 g of fat and 80 g of carbohydrate (fed
      state). Forearm substrate exchange was studied during 60 min of isometric forearm
      exercise (5 s contraction, 5 s relaxation). 3. In the fed state concentrations of
      plasma triacylglycerol (1510 +/- 150 versus 850 +/- 80 mumol/l, P < 0.01), blood
      ketone bodies (151 +/- 21 versus 80 +/- 10 mumol/l, P < 0.01) and plasma insulin
      (17 +/- 3 versus 7 +/- 1 m-units/l, P < 0.01) were elevated compared with the
      postabsorptive state; plasma glucose and non-esterified fatty acid concentrations
      were not significantly different. 4. Forearm blood flow and O2 consumption each
      increased about 6-fold during exercise, with no differences between the two
      nutritional states. The potential contribution of individual substrates to
      forearm O2 consumption (a calculation which is independent of blood flow) was
      assessed: for triacylglycerol it was significantly greater in the fed state (P <
      0.01). The sum of the potential contributions of triacylglycerol, non-esterified
      fatty acids, glucose and ketone bodies to forearm O2 consumption was
      significantly greater, both before and during exercise, in the fed than in the
      postabsorptive state (P < 0.05), implying the sparing of endogenous (forearm)
      fuels. 5. These studies highlight the potential for manipulation of substrate
      supply during exercise by feeding meals containing both carbohydrate and fat.

PMID- 8143428
TI  - Effect of noradrenaline on glycerol turnover and lipolysis in the whole body and
      subcutaneous adipose tissue in humans in vivo.
AB  - 1. The effect of infusion of noradrenaline (0.42 mumol min-1 kg-1) on the
      exchange of nonesterified fatty acids, glycerol and other metabolites across
      subcutaneous abdominal adipose tissue was investigated in five healthy subjects
      using an arteriovenous catheterization technique and measurement of adipose
      tissue blood flow using the 133Xe clearance technique. At the same time, the net
      rate of fat oxidation in the whole body was assessed by indirect calorimetry, and
      the turnover of glycerol in the whole body and in subcutaneous adipose tissue was
      estimated using [5-2H]glycerol, which was administered as a primed constant
      infusion for 1 h before (basal turnover) noradrenaline administration and
      continued during the 1 h of noradrenaline infusion. 2. The noradrenaline infusion
      increased the plasma noradrenaline concentration from a basal value of 0.9 +/-
      0.1 to 12.6 +/- 1.2 nmol/(mean +/- SEM) at 60 min. It also increased the
      arterialized concentration of glycerol by 50% (basal value 81 +/- 11 mumol/l-1)
      and that of plasma non-esterified fatty acids three-fold (basal value 357 +/- 86
      mumol/l). 3. Noradrenaline increased the net release of glycerol by adipose
      tissue three-fold and that of non-esterified fatty acids three- to four-fold.
      Although the ratio of non-esterified fatty acid to glycerol release by adipose
      tissue increased in all subjects from a mean value of 2.7 in the basal period to
      3.6 and 3.9 at 50 and 60 min of the noradrenaline infusion, respectively (P <
      0.02), at no time point did the ratio differ significantly from 3.0.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143429
TI  - Nitrogen homoeostasis in man: diurnal changes in nitrogen excretion, leucine
      oxidation and whole body leucine kinetics during a reduction from a high to a
      moderate protein intake.
AB  - 1. The adaptation of the diurnal cycle of nitrogen (N) homeostasis during a
      change in protein intake was investigated with diurnal measurements of N and
      leucine balance and turnover during a reduction from a high to a moderate protein
      intake in normal adults. 2. In experiment 1, during a 9 day period after a
      reduction from 1.82 to 0.77 g of protein day-1 kg-1, N excretion fell slowly at a
      similar rate in fed and fasted states so that the lowered intake was unable to
      replete any of the postabsorptive losses for 3 days. There was a marked negative
      N balance, which persisted throughout the study, although with a significant
      reduction in N losses in both fed and fasted states on day 4, balances during
      days 4-9 (-32.8 +/- 28.3 mg of N day-1 kg-1) were less negative than during days
      1-3 (-79.1 +/- 60.4 mg of N day-1 kg-1). 3. In experiment 2, during a 14 day
      period after a reduction from 1.89 to 0.77 g of protein day-1 kg-1, [1
      13C]leucine oxidation and turnover were measured by primed intravenous infusion,
      during fasting and feeding in subjects before and on days 3, 7 and 14 after the
      dietary change. Leucine oxidation fell by 32% (P < 0.05) on day 3 in the fed
      state and by 12% (P < 0.05) during fasting, falling further in each case by day 7
      with improved balance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143430
TI  - Effects of nitric oxide donors in vitro on the arachidonic acid-induced platelet
      release reaction and platelet cyclic GMP concentration in pre-eclampsia.
AB  - 1. Platelet activation in vivo occurs in healthy pregnancy and is more pronounced
      in pre-eclampsia. 2. This study has investigated: (i) the inhibitory potency of
      the nitric oxide donors 3-morpholinosydnonimine and sodium nitroprusside, on the
      platelet release reaction in vitro in non-pregnant, healthy pregnant and pre
      eclamptic women; (ii) the concentration of cyclic GMP during incubation of washed
      platelets with sodium nitroprusside in a separate group of non-pregnant, healthy
      pregnant and pre-eclamptic women. 3. The half-maximal inhibitory concentration of
      sodium nitroprusside, in the presence of a phosphodiesterase inhibitor, for
      inhibition of the platelet release reaction was lower in the pre-eclamptic
      subjects than in the non-pregnant subjects (P < 0.05). 4. Several of the pre
      eclamptic women were studied again postnatally. The half-maximal inhibitory
      concentrations of sodium nitroprusside and 3-morpholinosydnonimine were higher in
      the postnatal than in the antenatal sample (P < 0.02). 5. Peak platelet cyclic
      GMP responses to sodium nitroprusside were significantly higher in the pre
      eclamptic women than in the healthy pregnant and non-pregnant women. 6. These
      results suggest that platelets are more sensitive to the inhibitory effects of
      nitric oxide donors in pre-eclampsia.

PMID- 8143431
TI  - Altered dynamics of the circadian relationship between systemic arterial pressure
      and cardiac sympathetic drive early on in mild hypertension.
AB  - 1. This study was designed to test the hypothesis that simultaneous non-invasive
      assessment of the circadian variations in both intermittent arterial pressure and
      the continuous 24 h changes of spectral markers of cardiac neural control could
      provide new information on cardiovascular regulatory mechanisms, in hypertensive
      patients and normotensive subjects. To test this hypothesis we studied 18
      subjects with mild hypertension and 11 normotensive subjects in whom we recorded
      simultaneously non-invasive intermittent arterial pressure and Holter
      electrocardiogram for 24 h. We also studied the same subjects during resting and
      standing conditions in the clinical laboratory. 2. The normalized power of the
      low-frequency (approximately 0.1 Hz) spectral component of R-R interval
      variability, considered mainly a marker of sympathetic drive to the sino-atrial
      node, was, at rest, significantly higher in the hypertensive than in the
      normotensive subjects, as already reported. Moreover, the values of the low
      frequency component at rest recorded in the clinical laboratory were
      significantly correlated with those obtained from ambulatory recording during
      night rest. The decrease in the values of arterial pressure during the night-time
      was accompanied by a reduction in the power of the low-frequency component only
      in the case of normotensive subjects. Accordingly, the slope of the regression of
      the low-frequency component as a function of systolic arterial pressure during
      ambulatory recordings was steep in normotensive subjects and flat in hypertensive
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143432
TI  - Increased systolic blood pressure in adult rats induced by fetal exposure to
      maternal low protein diets.
AB  - 1. Possible associations between maternal nutrition in pregnancy and non
      communicable diseases of adulthood were assessed using a rat model. Rats were
      habituated to diets containing a range of protein levels (18, 12, 9 and 6% by
      weight), over a 14 day period, before mating. The low protein diets were
      maintained throughout pregnancy. Lactating mothers and their offspring were
      transferred to a standard chow diet (20% protein). 2. Pregnant rats demonstrated
      a graded response to the diets, with those fed 9 and 6% protein tending to
      consume less energy and gain less weight than 18% protein fed controls. Litter
      size and newborn death rates were not significantly altered by the low protein
      diets. 3. Offspring of 12 and 9% protein fed dams were grossly normal, gaining
      weight at a similar rate to those born to 18% protein fed control rats. Offspring
      of the 6% protein fed dams were smaller than pups from all other groups, over a
      21 week period. 4. At 9 weeks of age, systolic blood pressure was determined in
      the offspring. All offspring from the three low protein groups were found to have
      significantly elevated blood pressure (15-22 mmHg) relative to the control group.
      An inverse relationship between maternal protein intake and the systolic blood
      pressure of the offspring was observed. Blood pressure remained elevated in the
      offspring of the 9 and 6% protein fed dams until 21 weeks of age. The observed
      hypertension was associated with increased pulmonary angiotensin-converting
      enzyme activity in the low protein groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143433
TI  - Effect of citrate infusion on urinary aluminium excretion in the rat.
AB  - 1. Seven pairs of rats received 1 mmol/l aluminium citrate in their drinking
      water 5 days before the experiments. Five additional rats were treated
      identically. Six rats received the same food but drank distilled water. 2. After
      a 6 h fast, the animal was anaesthetized, the jugular vein and femoral artery
      were cannulated and the bladder was catheterized, after which an intravenous
      infusion of Hartmann's solution containing [14C]inulin was begun. The urine was
      collected at 20 min intervals and 1 ml of arterial blood was obtained before the
      end of each collection. After at least two basal collections, the infusion was
      modified to contain, in addition, 5 mmol/l NaHCO3 (control) or 5 mmol/l sodium
      citrate (experimental). The infusion rate, constant in each pair, differed
      between pairs across the range 60-125 mumol/min. 3. A total of eight collections
      was made per animal and urine flow, glomerular filtration rate, plasma and
      urinary aluminium and citrate were measured. 4. Control and experimental rats had
      a higher mean basal plasma aluminium level (0.39 +/- 0.21 mumol/l) than the six
      rats receiving distilled water (0.16 +/- 0.14 mmol/l, P < 0.001). The
      corresponding urinary aluminium excretion rates were similar (46 +/- 31 and 47 +/
      23 pmol/min, respectively). There was no significant difference between the
      basal values of any variable in the control and experimental rats. No significant
      change was observed in any variable during the infusion of NaHCO3 (controls).
      Among the experimental rats, there was no significant change in urine flow,
      glomerular filtration rate or plasma aluminium level.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8143434
TI  - Gender differences in urinary kallikrein excretion in man: variation throughout
      the menstrual cycle.
AB  - 1. Urinary kallikrein excretion was measured in healthy male subjects and in
      healthy pre- and post-menopausal females. 2. Urinary kallikrein excretion was
      shown to be constant throughout a 24 h period. Individual male subjects showed
      little fluctuation in urinary kallikrein excretion; within-subject variance
      accounted for 1.65% of the total. 3. Female subjects with ovulatory menstrual
      periods excreted significantly more kallikrein than post-menopausal females and
      males. 4. Pre-menopausal females showed a much greater within-subject variation
      in urinary kallikrein excretion and this could be related to the stage of the
      menstrual cycle, with significantly greater urinary kallikrein excretion in the
      luteal phase than in the follicular phase. 5. Plasma renin activity and plasma
      aldosterone concentration also showed a menstrual variation, with concentrations
      in the luteal phase being significantly higher than those in the follicular
      phase. 6. The rise in urinary kallikrein excretion in the luteal phase could be
      abolished by oral administration of the aldosterone antagonist spironolactone. 7.
      Urinary kallikrein excretion in post-menopausal females was similar to the range
      found in males, and showed no cyclic changes over a 4 week period. 8. Gender and
      menstrual status should be taken into account in studies of the physiological
      role of tissue kallikreins.

PMID- 8143435
TI  - Fluoride varnishes (Duraphat): a meta-analysis.
AB  - In the present article we analyze a series of studies designed to detect the
      caries preventive effect of Duraphat by means of meta-analysis. Meta-analysis is
      a collection of statistical methods designed to investigate and to summarize a
      series of investigations. It may be a valuable tool to complement traditional
      narrative reviews. During the last years meta-analysis has attracted increasing
      interest in sociology, psychology and medicine. In order to find previous studies
      concerned with the clinical effects of Duraphat we applied a systematic
      literature search. Papers were included independent of results when they
      fulfilled a checklist of well defined methodological selection criteria. In order
      to aggregate the results of the Duraphat-studies we used different complementary
      statistical approaches: Firstly, the so-called file drawer problem is considered.
      This may help to get a better insight into the problem of underreporting non
      significant results or publication bias. It was found to be very unlikely that
      underreporting of non-significant results could reverse the conclusion into an
      overall null-result. After that, the inhomogeneity between studies is
      investigated. The overall variation of caries reduction R is separated into two
      components: A between study component of variance and a variance pertaining to
      the individual studies (random effects model). It was found that the overall
      variation is dominated by the between studies variation and not by the sampling
      variation. Due to the pronounced variation between studies the confidence
      interval of the overall effect size (R = 0.38) is quite large (95%-Cl: 0.19
      0.57).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143436
TI  - Epidemiologic study of sound surface trends in a 10-year longitudinal study.
AB  - Longitudinal data of 589 men aged 30-65 yr, each followed for 10 yr, were
      analyzed to identify variables which may be associated with healthy tooth surface
      loss. A longitudinal linear growth curve model was used. As expected, older
      cohorts tended to have fewer sound surfaces (P < 0.02), but they also tended to
      have greater rates of sound surface loss (P < 0.01). Age, bone loss, number of
      teeth at baseline, gingivitis, pocket depth and calculus were individually
      correlated (P < 0.05) with the rate of sound surface loss. The number of filled
      or diseased surfaces at baseline was also marginally correlated (P < 0.06) with
      rate of sound surface loss.

PMID- 8143437
TI  - Comparison of glass-ionomer and resin-based fissure sealants: a 2-year clinical
      trial.
AB  - In recent years, the interest in the use of glass-ionomer materials as fissure
      sealants has increased. The aim of this study was to compare the retention and
      caries-preventive effect of glass-ionomer (Fuji III) and resin-based light-cured
      (Delton) fissure sealants. Three health center dentists applied the sealants to
      166 children; glass-ionomer sealants on one side and resin-based sealants on the
      contralateral side of the mouth. After 2 yr, one pair of molar teeth in the
      mouths of 151 children was compared. Twenty-six percent of glass-ionomer and 82%
      of resin-based sealants were totally present (P < 0.001). During the 2 yr, in
      both groups 4.6% of the sealed surfaces became carious. The results show that the
      retention of glass-ionomer sealants is markedly inferior to the resin-based
      sealants. In this study, however, no difference in caries increment on the sealed
      surfaces was observed. This may be due to the different mechanism of caries
      prevention for the sealant materials, or to the overall low caries activity of
      the participants.

PMID- 8143438
TI  - Dental caries and social factors in 12-year-old South African children.
AB  - Dental caries prevalence (percentage caries-free) and experience (DMFS) were
      recorded, in 414 12-yr-old Indian and 401 white children living in adjacent urban
      communities with the same fluoride concentration in the drinking water (0.21-0.33
      ppm) using WHO (11) criteria. Details of social factors: education level, family
      income, home space and occupants and parental occupation were obtained by
      questionnaire. Dental caries was significantly worse in the Indian children with
      regard to numbers caries-free (30%--white and 40%--Indian) and DMFS mean (sd)
      (3.65 (3.98) and 2.66 (3.49) working group, respectively). Social class, white or
      blue collar, family income and room to person ratio were significantly associated
      with dental caries in the white children but there were no significant
      associations in the Indian children. Multiple regression analysis showed race and
      sex to be significant factors.

PMID- 8143439
TI  - Factors affecting caries experience in French adolescents.
AB  - Three hundred French 14-15-yr-old adolescents were randomly selected. They were
      examined clinically and caries experience was determined by using the DMFS index.
      The aim of this investigation was to evaluate children's habits using a self
      administered questionnaire, to clarify the actual influence of well-known factors
      such as fluoride exposure, diet, oral hygiene and socioeconomic factors on caries
      experience and to stress those factors of primary importance. A multiple
      regression analysis revealed the variables which significantly contributed to
      explain DMFS scores in a final model: Age, sex, frequency of sweet consumption,
      use of standard or high fluoride toothpastes, bleeding during toothbrushing,
      living in St Yorre (F- = 0.45 mg/l). At a time when caries experience is
      decreasing, it seems that fluoride supply, snacking and oral hygiene are still
      independent and significant determinants of caries experience in French
      adolescents.

PMID- 8143440
TI  - Dental health habits of young families from southwestern Finland.
AB  - The dental care habits of parents and children as well as the associations of
      these habits were investigated in a follow-up study conducted in the Southwest of
      Finland. The background factors of the child's use of night-time juice were also
      studied. The families of the study were a representative sample of local young
      families with their first child. The study sample was obtained using stratified
      randomized cluster sampling and confidential questionnaires. Both the mother's
      and the father's toothbrushing habits were significantly associated with the
      child's toothbrushing habits with a cumulative effect. The mother's use of sugar
      was significantly associated with the child's sugar use habit. Infectious
      diseases at the age of 9-17 months had an increasing effect on the use of juice
      at night. Fathers and the youngest mothers, especially, need additional support
      not only for the demanding task of the upbringing of their child but also for the
      care of their own teeth.

PMID- 8143441
TI  - Effect of two preventive programs on oral health knowledge and habits among
      Brazilian schoolchildren.
AB  - The effect upon dental health knowledge and dental health behavior of a
      comprehensive and a less comprehensive preventive program was compared in a 3-yr
      follow up study. The comprehensive program included active participation of the
      students and parental involvement. The study group consisted of 186 Brazilian
      schoolchildren 13 yr of age at the start of the program. A reference group from
      another school of similar socioeconomic level was included in the analyses. The
      data were collected from questionnaires filled in by the children under
      surveillance after the completion of the program. Significant differences in
      knowledge as well as in reported behavior were observed. The children enrolled in
      the comprehensive program in general scored higher in dental health knowledge
      than did those in the less comprehensive program. However, the latter group of
      children seemed to have acquired more correct knowledge during the period than
      had the control and reference children. Similar results were obtained concerning
      reported dental health behavior.

PMID- 8143442
TI  - Social factors and self-assessed oral health in South Africa.
AB  - The question of what determines the dental needs of a population has been widely
      debated in the dental literature. Although there is no full agreement, the
      consensus is that substantial consideration should be given to the people's
      perceptions of what their needs are, based on self-assessment of their oral
      health and satisfaction with the appearance of their teeth. These perceptions
      (self-assessments) are likely to be shaped by their previous experiences with the
      dental service, their understanding of "normally" and knowledge of oral care,
      which are determined by social factors such as culture, class and race. The
      purpose of this paper is to examine self-assessed oral health in South Africa
      according to relevant social factors. In 1988/89 a National Oral Health survey,
      which included a social survey, was conducted. The data were collected by means
      of a structured interview, based on a questionnaire, with a sample of 4652 adults
      aged 20-64 yr. The variables examined in this paper formed part of the items in
      the questionnaire. There is a higher level of identification that "something is
      wrong with teeth" in (a) lower educational levels (53%-no formal education; 20%
      standard 10+); (b) lower income categories (43%-lowest; 16%-highest); (c) among
      Xhosa (66%), S. Sotho (58%) and Zulu (53%) speaking groups and (d) among Black
      people (54%). Similar trends are evident in the degree of satisfaction with the
      appearance of teeth. The results reveal differences in self-assessed oral health
      among people with different educational standards, income levels,
      linguistic/cultural characteristics as well as racial groups as defined by the
      Population Registration Act of 1950.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143443
TI  - Public knowledge/perceptions about AIDS transmission: concerns about use of
      dental services.
AB  - This telephone survey of 739 adults living in the State of Maryland (response
      rate 68.9%) examined the association between public perceptions and knowledge
      about the routes of transmission of AIDS, and concerns about contracting AIDS in
      a dental office and attitudes toward confidentiality of AIDS infected dentists
      and patients. The greatest areas of inaccuracies related to the risk of giving
      and receiving blood. Associations were demonstrated between public knowledge and
      concern about AIDS. Racial differences were found in both knowledge and concerns.
      Accurate dissemination of information to the public about AIDS is essential for
      the maintenance of public confidence and trust in the safety of dental offices
      and dental treatment.

PMID- 8143444
TI  - Age and order of eruption of primary teeth in Spanish children.
AB  - A longitudinal study on primary tooth eruption was performed in 114 Spanish
      children in two Primary Care Centers over 3 yr. Data from periodic observations
      and data collected by previously instructed parents was studied. Ages of tooth
      eruption were calculated for both sexes. Comparison between the two sides of the
      jaws showed a nonsignificant tendency towards earlier left side eruption.
      Comparison between maxillary and mandibular showed a significant earlier
      mandibular eruption for central incisors and second molars and a significant
      earlier maxillary eruption for lateral incisors. Comparison between sexes showed
      a tendency towards earlier eruption in boys for all teeth, significant only for
      mandibular central incisors, maxillary and mandibular lateral incisors and
      mandibular canines. Order of tooth eruption and its most frequent changes were
      also studied. When these findings were compared to studies performed in other
      populations it was concluded that ages and order of primary tooth eruption in
      Spanish children are similar to those found in other populations.

PMID- 8143445
TI  - A note concerning the caries preventive effect of Duraphat.
AB  - In a previous article (1) we analyzed a series of eight studies concerned with
      the effect of Duraphat in the prevention of dental caries by means of meta
      analysis. A random effects model was used to estimate an overall effect size of
      caries reduction R and the corresponding confidence interval. In the present
      short communication we complement this previous study by neglecting the within
      study variation to the overall variation which is dominated by between study
      variation. This allows us to include a larger number of studies and thus make
      fuller use of the available information. We estimate nonparametrical confidence
      intervals for effect sizes (caries reduction) by means of the "bootstrap method".
      The overall caries reduction R on permanent teeth (14 studies) was estimated to
      be: R = 0.38 (95%-CI: 0.25-0.50).

PMID- 8143446
TI  - Low levels of destructive periodontal disease in a rural population in west
      Bengal, India.

PMID- 8143447
TI  - Caries prevalence and treatment need amongst children of Dharavi, Bombay, India.

PMID- 8143448
TI  - Four-year study of caries inhibition of intensive Duraphat application in 11-15
      year-old children.
AB  - The purpose of the study was to evaluate the caries preventive effect and cost of
      an intensive application of Duraphat varnish, added to the regular preventive
      program for 11-15-yr-old children in a Swedish Dental Community Clinic. In 1987,
      the 134 11-yr-old children in Floda were divided into two groups, every second
      child to each. Children with fixed orthodontic appliances were excluded. The test
      group received three applications of Duraphat varnish during 1 week, once a year,
      by a dental nurse. The control group received one application at the annual check
      up. Both groups were included in the regular preventive program at the clinic.
      The total time cost for the clinic was estimated and used to calculate the cost
      per hour for dentists and nurses. The caries increment and progression were
      estimated both by routine diagnosis and by a careful study of radiographs taken
      at the beginning and end of the study period. There was a small caries increment
      and progression in the test group as compared to the control group. The
      difference was statistically significant for all aspects studied. The costs were
      about the same in both groups but more time was used in the test group. The
      administrative effort for the staff was considerable for the intensive Duraphat
      application.

PMID- 8143449
TI  - Misoprostol: the experience of women in Fortaleza, Brazil.
AB  - Misoprostol is used by women in Brazil in case of unwanted pregnancy to attempt
      abortion. This paper reports the characteristics, pattern of misoprostol use and
      opinions of a group of 102 women (median age 25 years, range 16-49 years), from
      Fortaleza, capital of Ceara state, who had used misoprostol to attempt abortion.
      Seventy-five percent were women of lower social class, 58% had less than 8 years
      of education and 46% were never married. Misoprostol was used for the first
      induced abortion by 65 women. Modal dose was 4 tablets--200 micrograms of
      misoprostol each--most frequently 2 tablets by oral route and 2 tablets by
      intravaginal route. This pattern of use was associated with the highest rate of
      abortion, mainly at 9-12 weeks of amenorrhea. Fifty-five percent of women had no
      pregnancy test; 41% had 8 weeks or less of amenorrhea. Curettage was performed in
      49 of 84 women who reported abortion and in 41 of 43 women who entered the
      hospital. Infection and uterine perforation were the complications described.
      Seventy-two percent of women were in favor of legalization of abortion, but 52%
      were also in favor of the prohibition of misoprostol sales; 66% would not repeat
      misoprostol use and 53% would not suggest it to a friend. The poorest women were
      less favorable to misoprostol ban. Despite the current lack of safer
      alternatives, misoprostol does not seem a satisfactory solution to illegal
      abortion in Brazil.

PMID- 8143450
TI  - Early induction of abortion by a combination of oral mifepristone and misoprostol
      administered by the vaginal route.
AB  - Medically induced abortion using a new regimen of oral mifepristone 600 mg and
      vaginal misoprostol 800 micrograms (PGE1 analogue) was carried out in 100 women.
      Abortion occurred in all patients without resort to surgery. In 99 women, the
      abortion occurred within 4 hours of the administration of the prostaglandin.
      Sixty-seven patients did not request any form of analgesia. This regimen is
      highly effective, has a low incidence of side effects (mainly gastrointestinal)
      and appears to be highly acceptable to women.

PMID- 8143451
TI  - Cervical smooth muscle contractile activity after treatment with mifepristone and
      progesterone.
AB  - Contractile activity of the uterine cervix in vitro was studied in women
      pretreated with mifepristone 200 m chi 2 or progesterone suppositories 100 mg
      before cervical dilatation and vacuum aspiration in the first trimester.
      Mifepristone increased the dilatation of the cervix as measured prior to
      operation whereas progesterone had no effect. Spontaneous muscle activity and
      contraction frequency were not affected by either drug. Neither the inhibitory
      response to PGE2 nor the excitatory response to noradrenaline were significantly
      different from that in placebo-treated women. It is concluded that the cervical
      smooth muscle has no major role in the dilatatory effect of mifepristone in the
      cervical canal.

PMID- 8143452
TI  - Carbohydrate metabolism studies after one year of using an oral contraceptive
      containing gestodene and ethinyl estradiol.
AB  - The objective of the study is to evaluate the effects of a gestodene-containing
      oral contraceptive on carbohydrate metabolism. The design of the study is
      prospective. The setting is at University of South Florida Outpatient Unit. The
      patients consisted of twenty-three normal women desiring contraception. Serum
      glucose and insulin levels were measured during a three-hour glucose tolerance
      test at control time and after one year of drug use. RESULTS: All of the one-year
      glucose values were significantly elevated as well as the fasting and three-hour
      insulin values. These changes were mostly confined to women over 26 years of age
      and not in the younger 18 to 23 year olds. An oral contraceptive containing 75
      micrograms of gestodene and 30 micrograms of ethinylestradiol can significantly
      alter carbohydrate metabolism in older women.

PMID- 8143453
TI  - Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing
      levonorgestrel at a rate of 27 micrograms/24 hours: a pilot study.
AB  - The pharmacokinetic and pharmacodynamic effects of vaginal rings releasing
      levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24 h were studied in a
      group of 12 normally menstruating women during 90 days of continuous use (i.e.,
      during three 30-day treatment segments). Blood samples were drawn immediately
      before insertion, 15 and 30 min, as well as 1, 2, 4, 8, 12 and 24 h after
      insertion of the rings, and thereafter three times weekly throughout the study
      for the analysis of L-NOG, estradiol, progesterone and sex hormone-binding
      globulin (SHBG). Endometrial biopsies were obtained for a morphometric analysis
      in a pre-treatment (control) cycle and in the 6th and 10th weeks of treatment.
      The peak of average L-NOG levels was reached within two hours after the insertion
      of rings. Until 24 h after insertion, the levels did not change significantly.
      Thereafter, a decrease at a rate of 0.2% per day was initiated. The L-NOG and
      SHBG levels were highly correlated. This was seen for both the pre-treatment SHBG
      vs L-NOG (r = 0.96) and the treatment SHBG vs L-NOG levels (r = 0.92). There was
      a significant (p < 0.001) decrease of SHBG levels due to treatment. During the
      total of 36 treatment segments, a normal ovarian function was seen in 47% of the
      segments. The women were anovulatory and had an inadequate lutal function in 28%
      and 25% of segments, respectively. No correlation between the L-NOG levels and
      ovarian reaction to treatment was found. The use of L-NOG induced significant
      changes in the endometrium; the number of glands/mm2 decreased after 6 (p < 0.02)
      and 10 weeks of use (p < 0.01). Also, the diameter of glands and the occurrence
      of vacuolated cells decreased significantly (p < 0.02 and p < 0.005,
      respectively). None of the endometrial parameters or dating was correlated with
      the ovarian reaction to treatment, indicating independent endometrial effects of
      L-NOG.

PMID- 8143454
TI  - A comparative study of the properties between human fibronectin isolated from
      placenta of early and term pregnancy.
AB  - Fibronectin from human early pregnancy (5-8 weeks) placenta (epFN) has been
      isolated by 2M urea-PBS extraction and purified by heparin-Sepharose 4B affinity
      chromatography followed by Sepharose CL-6B gel filtration, and compared with that
      of term placenta (tpFN). According to the analysis on SDS-polyacrylamide gel
      electrophoresis (SDS-PAGE) and Western-blots, epFN was similar to tpFN; both are
      composed of two 250 KD subunits, larger than 220 KD subunits of plasma
      fibronectin (pFN). They reacted with antibodies against pFN and monoclonal
      antibodies (mAbs) raised against three mainly functional domains of amniotic
      fluid fibronectin (amFN), respectively. However, the affinity of epFN with mAb
      against heparin-binding domain was stronger than that with mAb against gelatin
      binding domain; this phenomenon could not be observed with tpFN and pFN. The
      results of lectin-binding capacity indicated that epFN was not only distinct from
      pFN but also from tpFN on its carbohydrate composition. We also found there were
      much more FN-binding proteins in early placenta than in term placenta. The
      significance of these results are discussed.

PMID- 8143455
TI  - Long-term contraceptive effects of intrauterine neem treatment (IUNT) in bonnet
      monkeys: an alternate to intrauterine contraceptive devices (IUCD).
AB  - Antifertility effects of intrauterine neem treatment (IUNT) was studied in bonnet
      monkeys. A single administration of 1 ml of neem oil by an intrauterine
      insemination catheter blocked fertility for 7 to 12 months. The effect was,
      however, reversible as all the animals became pregnant subsequently and delivered
      normal babies. The neem oil treatment had no adverse effect on menstrual
      cyclicity and ovarian functions. The uterus of neem-treated animals showed normal
      morphology. Immunohistological studies, however, demonstrated a significant
      increase in the number of MHC-II antigen-positive cells in the uterine
      endometrium following neem treatment, indicating enhanced antigen-presenting
      ability of the uterus; a feature that may be related to the observed
      antifertility effect of neem oil. The present investigation demonstrates that an
      IUNT can be used for long-term, reversible contraception, without any apparent
      side effects, and that the method could provide an alternate to currently used
      intrauterine contraceptive devices (IUCD).

PMID- 8143456
TI  - Introducing the low-dose pill to Bangladesh; issues of continuation and failure.
AB  - In response to government plans to introduce a low-dose pill to the national
      family planning program of Bangladesh, a comparison of the performance of low
      dose and standard-dose pills among a rural Bangladeshi population was conducted.
      Continuation rates were found to be better among users of the low-dose pill and
      there was no evidence that failure rates were higher. The relative risk (standard
      dose vs. low-dose) over the first 30 months following adoption was 1.25 for first
      method continuation, and 1.29 for extended use failure. This paper, thus,
      provides evidence that low-dose pills may be a suitable method of contraception
      for rural Bangladeshi women.

PMID- 8143457
TI  - Antiendotoxin approaches to septic shock therapy.

PMID- 8143458
TI  - Ribavirin in severe respiratory syncytial virus infection.

PMID- 8143459
TI  - Pulmonary artery catheterization--at the crossroads?

PMID- 8143460
TI  - Evaluation of blood gas monitors: performance criteria, clinical impact, and
      cost/benefit.

PMID- 8143461
TI  - Monitoring and therapy for young trauma patients.

PMID- 8143462
TI  - Importance of interleukin-8 and chemokines in organ injury and shock.

PMID- 8143463
TI  - Human neutrophil bactericidal/permeability-increasing protein reduces mortality
      rate from endotoxin challenge: a placebo-controlled study.
AB  - OBJECTIVES: To study the toxicology and pharmacology of the endotoxin
      neutralizing agent, bactericidal/permeability-increasing protein. DESIGN:
      Prospective, randomized, placebo-controlled laboratory study. SETTING: Academic
      research laboratory. SUBJECTS: CD-1 mice (n = 259); Sprague Dawley rats (n = 26);
      New Zealand White rabbits (n = 19). INTERVENTIONS: Pharmacokinetics of
      intravenously injected bactericidal/permeability-increasing protein was assessed
      in mice. Toxicology was tested in mice and rats. Efficacy of intravenously
      administered bactericidal/permeability-increasing protein as an endotoxin
      neutralizing agent was tested in mice, rats, and rabbits. MEASUREMENTS AND MAIN
      RESULTS: Administration of a single 10-mg/kg bolus injection of
      bactericidal/permeability-increasing protein resulted in no alterations in
      hematologic, renal, or hepatic function, activity level, or weight gain in
      animals observed over a 7-day study period. A single bolus injection (10 mg/kg)
      of bactericidal/permeability-increasing protein protected 15 of 16 mice from a
      lethal endotoxin challenge (mortality rate 1/16 [6.25%]) compared with a 100%
      (16/16) mortality rate in the saline-treated controls (p < .001).
      Bactericidal/permeability-increasing protein administered up to 1 hr after
      endotoxin provided significant protection against lethal endotoxin challenge.
      Furthermore, bactericidal/permeability-increasing protein reduced the induration
      and dermal necrosis observed in the localized dermal Shwartzman reaction.
      CONCLUSIONS: Bactericidal/permeability-increasing protein is a potent
      antiendotoxin that neutralizes endotoxin in vivo and prevents mortality in animal
      models of lethal endotoxemia.

PMID- 8143464
TI  - Endotoxin-binding and -neutralizing properties of recombinant
      bactericidal/permeability-increasing protein and monoclonal antibodies HA-1A and
      E5.
AB  - OBJECTIVE: To compare the endotoxin-binding and -neutralizing properties of
      bactericidal/permeability-increasing protein, the human monoclonal antiendotoxin
      antibody HA-1A, and the murine antiendotoxin antibody E5. DESIGN: Prospective,
      randomized, placebo-controlled laboratory study. SETTING: Biotechnology company
      research laboratory. SUBJECTS: Female CD-1 mice. INTERVENTIONS: Recombinant
      bactericidal/permeability-increasing protein, HA-1A, a human immunoglobulin M
      monoclonal antibody raised against Escherichia coli J5 (Rc) endotoxin, and E5, a
      murine immunoglobulin M monoclonal antibody raised against E. coli J5 endotoxin,
      were compared in the following assays: a) binding to rough lipopolysaccharide
      immobilized onto microtiter plates; b) inhibition of lipopolysaccharide activity
      in the limulus amebocyte lysate assay; c) inhibition of lipopolysaccharide
      induced cytokine release in whole blood; and d) protection against lethal
      endotoxin challenge in CD-1 mice. MEASUREMENTS AND MAIN RESULTS: The binding
      affinity of bactericidal/permeability-increasing protein for immobilized
      lipopolysaccharide is apparently greater than the binding affinity of HA-1A or
      E5. Bactericidal/permeability-increasing protein neutralized lipopolysaccharide
      activity in the chromogenic limulus amebocyte lysate assay, while neither
      monoclonal antibody inhibited lipopolysaccharide activity. Similarly,
      bactericidal/permeability-increasing protein reduced lipopolysaccharide-mediated
      tumor necrosis factor production in human whole blood in vitro, whereas
      monoclonal antibodies had slight (HA-1A) or no (E5) effect on lipopolysaccharide
      activity in this system. Administration of bactericidal/permeability-increasing
      protein gave > 90% protection against an LD60 dose of endotoxin in CD-1 mice,
      while treatment with HA-1A or E5 did not improve survival rate. CONCLUSIONS:
      Neither monoclonal antibody was as effective as bactericidal/permeability
      increasing protein at binding or neutralizing endotoxin in vitro or in vivo. The
      potent endotoxin-binding and -neutralizing properties of
      bactericidal/permeability-increasing protein indicate that it might be useful in
      the treatment of endotoxin-related disorders in humans.

PMID- 8143465
TI  - Aerosolized ribavirin in mechanically ventilated children with respiratory
      syncytial virus lower respiratory tract disease: a prospective, double-blind,
      randomized trial.
AB  - OBJECTIVE: To study the effect of ribavirin aerosol therapy on the immediate
      clinical course of mechanically ventilated children with respiratory syncytial
      virus lower respiratory tract disease. DESIGN: Prospective, randomized, double
      blind, placebo-controlled study. SETTING: Pediatric intensive care unit (ICU) of
      a university teaching hospital. PATIENTS: Forty-one children requiring mechanical
      ventilation for respiratory syncytial virus lower respiratory tract disease.
      INTERVENTIONS: Patients were stratified by the presence or absence of and
      underlying disease and then randomized to receive aerosolized ribavirin (20
      mg/mL) or saline for 18 hrs/day for 5 days or until endotracheal extubation,
      whichever came first. MEASUREMENTS AND MAIN RESULTS: Dependent variables included
      the time course of the illness and the change in FIO2, ventilatory rate,
      PaO2/FIO2 ratio, and ventilatory-efficiency index of patients while they received
      aerosol therapy. Ribavirin- and placebo-treated patient groups were not
      significantly different in the number of ventilator days (6.4 +/- 6.9 vs. 8.2 +/-
      10.1; p = .5), oxygen days (10.8 +/- 7.7 vs. 12.2 +/- 11.8; p = .9), ICU days
      (7.9 +/- 7.0 vs. 10.3 +/- 11.0; p = .7), or hospital days (12.9 +/- 9.7 vs. 16.2
      +/- 14.0; p = .6) after the initiation of aerosol therapy. The change in FIO2,
      ventilatory rate, PaO2/FIO2 ratio, or ventilatory-efficiency index did not differ
      between the two groups. No ventilator malfunction was observed. There were six
      deaths caused by intractable hypoxemia in patients with underlying
      cardiopulmonary disease. Four of these deaths were in the placebo group and two
      in the ribavirin group (p = .5). CONCLUSIONS: Ribavirin aerosol therapy can be
      safely administered to mechanically ventilated children with severe respiratory
      syncytial virus lower respiratory tract disease. However, this therapy does not
      appear to affect immediate clinical outcome in such patients.

PMID- 8143466
TI  - Pulmonary artery catheterization in critically ill patients: a prospective
      analysis of outcome changes associated with catheter-prompted changes in therapy.
AB  - OBJECTIVE: To evaluate physician accuracy in predicting patients' hemodynamic
      profiles, associated morbidities, rates of change in therapy resulting from
      catheterization, and the outcome variations associated with such change before
      the insertion of a pulmonary artery catheter. DESIGN: Prospective, descriptive,
      cohort study with no interventions. SETTING: Medical intensive care unit (ICU) of
      a university hospital. PATIENTS: One hundred twelve catheterizations performed in
      112 patients without acute myocardial infarction. In 43 cases, catheterizations
      were indicated because of circulatory shock that was unresponsive to two standard
      therapeutic measures. MEASUREMENTS AND MAIN RESULTS: Before catheterization,
      physicians were asked to predict the hemodynamic profile of the patients who were
      to be catheterized, and to provide a plan for therapy. After catheterization,
      each patient's chart was reviewed and compared with precatheterization
      predictions. Hemodynamic profiles were correctly predicted in only 56% of the
      cases. Information obtained from pulmonary artery catheters prompted changes in
      therapy in 58% of all cases and in 63% of patients in shock who were unresponsive
      to standard therapy. Modifications varied among hemodynamic profiles, from 33%
      (fluid overloaded) to 87% (hypovolemia). Complications occurred in 11
      catheterizations, but only two complications required therapy (pneumothorax [n =
      1] and one episode of arrhythmia). No systemic infection occurred, and all blood
      cultures sampled through catheters before the catheters were withdrawn were
      sterile. In the entire group of patients, those patients in whom catheterization
      induced a change in therapy and those patients in whom no change in therapy
      occurred had similar precatheterization characteristics and mortality rates.
      However, in the subgroup of patients in shock that was unresponsive to standard
      therapy, the mortality rate was significantly lower when the assessment of
      hemodynamic data led to a change in therapy (59% vs. 100%, p = .009), despite
      identical precatheterization characteristics. CONCLUSIONS: Prompted by assessment
      of pulmonary artery catheter measurements in patients with circulatory shock who
      were unresponsive to standard therapeutic measures, a change in therapy for these
      patients was associated with an improved prognosis, independent of other
      variables influencing outcome.

PMID- 8143467
TI  - Continuous intra-arterial blood gas and pH monitoring in critically ill patients
      with severe respiratory failure: a prospective, criterion standard study.
AB  - OBJECTIVE: To evaluate the routine clinical performance of a new intra-arterial
      fiberoptic blood gas sensor that provides continuous PO2, PCO2, and pH
      monitoring. DESIGN: Criterion standard study under routine clinical conditions.
      SETTING: Intensive care unit (ICU) in a university hospital. PATIENTS: Twenty-two
      sensors were tested in 13 patients with acute respiratory failure, including two
      patients receiving veno-venous extracorporeal lung assist. Patient selection was
      based on the necessity of frequent blood gas monitoring. MEASUREMENTS: Sensor
      deprived PO2, PCO2, and pH values were compared with values obtained using two
      different conventional laboratory blood gas analyzers located in the ICU. The
      median study period was 72 hrs per sensor (range 8 to 170 hrs). The quality of
      blood pressure readings with the sensor introduced through the arterial catheter
      was assessed by a grading system. RESULTS: Mean differences between sensor
      derived values and the average values of the two conventional blood gas analyzers
      were as follows: PO2 -2.4 +/- 6.5 (SD) torr (-0.3 +/- 0.9 kPa), PCO2 -2.9 +/- 3.9
      torr (-0.4 +/- 0.5 kPa), and pH -0.04 +/- 0.03. Correlation coefficients were
      0.99 (PO2), 0.94 (PCO2), and 0.89 (pH), respectively. The agreement between the
      two methods for PO2 measurement was better for the clinically important range of
      values (PO2 < 150 torr [< 20 kPa]) than for all measured PO2 values (range 30 to
      522 torr [4 to 69.6 kPa]). Blood withdrawal and pressure readings were not
      adversely affected by the sensor. No side effects due to the insertion of the
      sensor were observed. CONCLUSIONS: The degree of agreement of intra-arterial
      blood gas sensor values with conventional blood gas analysis is within an
      acceptable range for routine clinical purposes. Acute changes in measured values
      are detected reliably. Continuous intra-arterial blood gas analysis can add
      substantially to the safety of patients with acute respiratory failure and can
      reduce blood sampling requirements for blood gas analysis.

PMID- 8143468
TI  - A multiparameter sensor for continuous intra-arterial blood gas monitoring: a
      prospective evaluation.
AB  - OBJECTIVE: To compare measurements of arterial blood gases made by a new
      continuous intra-arterial blood gas monitor with measurements in a standard blood
      gas analyzer in patients in the general and cardiac intensive care units. DESIGN:
      Criterion standard study. SETTING: The cardiac surgical and the general medical
      intensive care units of a tertiary referral center. PATIENTS: Thirteen
      consecutive patients requiring mechanical ventilation and blood gas monitoring.
      INTERVENTIONS: All patients had a blood gas sensor placed through a 20-gauge
      cannula inserted into the radial artery. The duration of monitoring ranged from
      9.42 to 117.45 hrs. MEASUREMENTS AND MAIN RESULTS: A total of 158 simultaneous
      measurements of pH, PCO2, and PO2 were made from the sensor and the blood gas
      analyzer, and the bias and precision were calculated on all measured parameters.
      The overall bias +/- precision values were 0.01 +/- 0.06 for pH, 1.4 +/- 4.8 torr
      (0.2 +/- 0.7 kPa) for PCO2, and 2.8 +/- 25.6 torr (0.4 +/- 3.4 kPa) for PO2. The
      bias and precision for PO2 measurements that were < 150 torr (< 20 kPa) were 0.45
      +/- 20.7 torr (0.1 +/- 2.8 kPa). The bias and precision for values of PO2 that
      were > 150 torr (> 20 kPa) were -8.1 +/- 28 torr (-1.1 +/- 3.8 kPa). The mean in
      vitro 90% response times of pH, PCO2, and PO2 sensors were found to be 78, 143,
      and 70 secs, respectively. There were no instances of any complications
      attributable to the sensor. CONCLUSIONS: The continuous intra-arterial blood gas
      monitor tested in this study measures and trends arterial blood gases with an
      acceptable level of clinical accuracy. Longevity and safety of sensor function
      have also been demonstrated.

PMID- 8143469
TI  - Use of arterial blood with bedside glucose reflectance meters in an intensive
      care unit: are they accurate?
AB  - OBJECTIVE: To compare blood glucose values obtained from two different sampling
      sites (arterial catheter and capillary from finger puncture), which were analyzed
      by a bedside reflectance meter. A sample was also analyzed by standard methods
      (oxygen electrode oxidation in the laboratory). DESIGN: Prospective, cross
      sectional clinical study. SETTING: Cardiovascular intensive care unit (ICU)
      designed for postoperative open-heart surgery patients in a 1,100-bed medical
      center. PATIENTS: Sequential sample of 50 patients immediately after open-heart
      surgery. MEASUREMENTS AND MAIN RESULTS: The blood glucose concentration of each
      patient was analyzed on the patient's arrival to the ICU (immediately
      postoperatively) by three methods: one blood specimen was obtained from an
      arterial catheter, divided and analyzed either at the bedside by a reflectance
      meter (glucose method 1) or in the hospital laboratory (glucose method 2);
      another sample was obtained by lancing the fingertip and the glucose
      concentration was analyzed at the bedside in the same reflectance meter (glucose
      method 3). Using paired analyses to compare the mean glucose values of the
      bedside arterial whole blood sample (method 1) with the arterial serum sample
      (method 2) demonstrated that the glucose concentration in the arterial whole
      blood sample (method 1) was significantly (p < .001) higher. For 46 of 50
      comparisons, the glucose value in the arterial whole blood sample (method 1) was
      higher, with a mean difference of 30 mg/dL (1.7 mmol/L). Although the mean
      difference was reduced to 10 mg/dL (0.6 mmol/L) when the arterial whole blood
      sample (method 1) was corrected for the hematocrit (i.e., < 35% [< 0.35]), the
      mean glucose concentration in the arterial whole blood samples (method 1)
      remained statistically higher (p < .05). The glucose concentration in the
      arterial serum sample (method 2) was significantly higher than the value
      determined from the bedside capillary sample (method 3) before (p < .05) and
      after (p < .001) correction for hematocrit. The difference in mean glucose
      concentrations between the arterial serum sample (method 2) and bedside capillary
      sample (method 3) was 9 mg/dL (0.5 mmol/L) when the capillary specimen (method 3)
      was not corrected for hematocrit. This difference increased to 21 mg/dL (1.2
      mmol/L) when low hematocrit values were considered and appropriate adjustments of
      the glucose values were made. At the bedside, one can accurately correct arterial
      whole blood glucose values to correspond to laboratory values by the following
      formula: (0.94 x arterial whole blood glucose) + (4.6 x hematocrit) + (-16.5 x
      [37 degrees C--patient's temperature])--132 = laboratory glucose value.
      CONCLUSIONS: Since arterial whole blood samples give higher glucose results than
      arterial serum, the use of arterial whole blood in combination with reflectance
      meters must be recommended with caution. This caution is especially advised if
      the glucose values obtained with arterial whole blood are used in conjunction
      with a sliding scale of insulin, which depends on threshold concentrations of
      glucose. In our hospital, use of arterial whole blood in combination with
      reflectance meters could have resulted in an incorrect dose of insulin in 31 of
      50 patients.

PMID- 8143470
TI  - Efficacy of albumin supplementation in the surgical intensive care unit: a
      prospective, randomized study.
AB  - OBJECTIVE: To determine the efficacy of supplemental 25% albumin in reducing
      morbidity and mortality rates in the surgical intensive care unit (ICU). DESIGN:
      Prospective, randomized, unblinded clinical study. SETTING: Surgical ICU in a
      community hospital. PATIENTS: Two hundred nineteen patients with admission
      circulating albumin concentrations of < 3.0 g/dL (< 30 g/L). The groups were well
      matched regarding age, sex, Acute Physiology and Chronic Health Evaluation II
      scores and initial circulating albumin concentrations. INTERVENTIONS: The
      treatment group (n = 116) received 37.5 g/day of albumin until the circulating
      albumin concentration increased to > 3.0 g/dL (> 30 g/L). The control group (n =
      103) received no supplemental albumin. Both groups received standard nutritional
      support. MEASUREMENTS AND MAIN RESULTS: The complication rate was 44% in the
      albumin group vs. 36.9% in the controls (p = .29). The albumin patients had a
      mortality rate of 10.3% vs. 5.8% in the control group (p = .22). There were no
      significant differences between the groups in the number of days spent receiving
      mechanical ventilation or in the tolerance to tube feedings. CONCLUSIONS: Routine
      supplemental administration of 25% albumin is expensive and offers no apparent
      outcome advantage and should be abandoned in the treatment of patients in the
      surgical ICU.

PMID- 8143471
TI  - Alveolar-arterial oxygen gradients before extracorporeal life support for severe
      pediatric respiratory failure: improved outcome for extracorporeal life support
      managed patients?
AB  - OBJECTIVE: Recent reports have described the usefulness of the alveolar-arterial
      oxygen tension difference (P[A-a]O2) in predicting mortality in children with
      acute respiratory failure managed with mechanical ventilation. We reviewed our
      experience with extracorporeal life support for acute pediatric respiratory
      failure and specifically examined P(A-a)O2 measurements during the 24 hrs before
      extracorporeal life support to determine if defined cutoffs established with
      conventional mechanical ventilation were applicable to extracorporeal life
      support survival. DESIGN: Retrospective, case-series chart review. SETTING: A
      university tertiary medical center. PATIENTS: Infants and children (n = 36), one
      month to 18 yrs of age, with severe life-threatening respiratory failure who were
      believed to have failed conventional mechanical ventilatory support.
      INTERVENTIONS: Veno-venous or veno-arterial extracorporeal life support.
      MEASUREMENTS AND MAIN RESULTS: From 1982 to 1992, we managed 36 pediatric
      patients with severe respiratory failure using extracorporeal life support. We
      identified 28 patients who had P(A-a)O2 values of > 400 torr (> 53.3 kPa) for the
      24-hr time period before placement on bypass. At the time of bypass initiation,
      all blood gas and mechanical ventilator parameters except PaCO2 showed trends of
      worsening pulmonary function, compared with measurements done 24 hrs before
      bypass initiation. Oxygenation-related variables showed statistically significant
      worsening trends when measured 24 hrs before bypass, compared with the time of
      bypass: P(A-a)O2 539 vs. 582 torr (71.9 vs. 77.6 kPa), p < .01; PaO2/FIO2 ratio
      70 vs. 57 torr (9.3 vs. 7.6 kPa), p < .05; oxygenation index 32 vs. 47 cm
      H2O/torr, p < .01; and FIO2 0.94 vs. 0.98, p < .05. Sixty-one percent of
      extracorporeal life support-managed patients (17 of 28) survived their life
      threatening respiratory illness to be discharged home. CONCLUSIONS: Based on
      previous reports of the utility of P(A-a)O2 measurements to predict mortality,
      our preliminary evidence suggests that extracorporeal life support results in 62%
      survival for pediatric respiratory failure patients predicted to have no chance
      of survival using conventional mechanical ventilation. Prospective, randomized
      trials of children with severe acute respiratory failure managed with mechanical
      ventilation vs. extracorporeal life support may be indicated.

PMID- 8143472
TI  - Use of pulse oximetry to monitor venous saturation during extracorporeal life
      support.
AB  - OBJECTIVE: To assess the ability of two different pulse oximeters to display
      continuous venous oxygen saturation through an extracorporeal bypass circuit with
      a degree of accuracy comparable to direct in-line oximetry. DESIGN: Prospective,
      comparison study of pulse oximeters (test oximeter 1 or test oximeter 2) and an
      in-line oximeter (test oximeter 3). SETTING: A tertiary care neonatal intensive
      care unit. PATIENTS: Sixty-five consecutive neonates with severe
      cardiorespiratory failure undergoing extracorporeal life support. INTERVENTIONS:
      The accuracy of the oximeters was determined by simultaneously comparing the
      saturation displayed by the pulse oximeters (test oximeters 1 and 2) and/or the
      in-line oximeter (test oximeter 3) with the measured fractional venous oxygen
      saturation obtained at regular intervals from the extracorporeal circuit. MAIN
      OUTCOME MEASURES: Venous oxygen saturation was the criterion standard used to
      determine accuracy. Bias was defined as the mean difference between observed
      pulse oximeter or in-line oximeter values and the measured venous oxygen
      saturation. Mean biases were calculated for venous oxygen saturation measurements
      between 55% and 99% at intervals of 10%. Precision (the standard deviation of the
      bias) was calculated for low (55% to 75%), medium (76% to 81%), and high (82% to
      99%) venous oxygen saturation values. A total of 983 venous oxygen saturation
      measurements were made and compared with simultaneous oximeter readings from test
      oximeter 1 (n = 600), test oximeter 2 (n = 478), and test oximeter 3 (n = 587).
      RESULTS: Test oximeter 1 was the most precise instrument at each level of venous
      oxygen saturation (SD, 4.0 to 4.8). Test oximeter 3 demonstrated the most
      consistent mean bias (range, 8), but was the most inaccurate oximeter across all
      levels of venous oxygen saturation. CONCLUSIONS: In addition to its known
      clinical usefulness, pulse oximetry may serve as an adequate substitute for in
      line oximetry during extracorporeal life support.

PMID- 8143473
TI  - Hemodynamic responses to shock in young trauma patients: need for invasive
      monitoring.
AB  - OBJECTIVE: To determine whether early invasive monitoring is necessary in young
      trauma patients. DESIGN: A prospective study. SETTING: Surgical intensive care
      unit (ICU) at an inner-city, Level I trauma center. PATIENTS: Thirty-nine
      patients < 40 yrs of age, who required operative therapy for penetrating trauma
      and who received > 6 units of intraoperative blood. INTERVENTIONS: Invasive
      hemodynamic monitoring, with percutaneous insertion of arterial and pulmonary
      artery catheters. Vital signs, hemodynamic and oxygen transport values, and
      laboratory tests were obtained at 1, 8, and 24 hrs postoperatively. Oxygen
      delivery was increased until a normal serum lactate concentration and a state of
      nonflow-dependent oxygen consumption were achieved. MEASUREMENTS AND MAIN
      RESULTS: Despite normal heart rate, blood pressure, and urine output, only five
      (15%) patients achieved an optimized state at 1 hr postoperatively. Of the other
      34 patients, two patients achieved an optimized state with volume infusion alone
      and 32 (82%) patients required inotropes. Five (12%) patients never achieved an
      optimized state and died within hours of their arrival to the ICU. Two other
      patients achieved an optimized state but died of sepsis and organ failure. The
      other 32 (82%) patients achieved an optimized state within 24 hrs and survived.
      The hemodynamic values of survivors at 1 hr postoperatively showed a
      significantly lower pulmonary vascular resistance and serum lactate
      concentration, and a significantly higher oxygen delivery and mixed venous oxygen
      saturation, when compared with the values of nonsurvivors. At 24 hrs
      postoperatively, survivors also had a significantly lower pulmonary vascular
      resistance and serum lactate concentration, and significantly higher oxygen
      delivery than nonsurvivors. Survivors' oxygen consumption was also higher than
      the oxygen consumption of nonsurvivors. CONCLUSIONS: Our data demonstrate that
      young trauma patients have substantial but clinically occult myocardial
      depression after shock, and most of these patients require inotropes to optimize
      and clear circulating lactate. Early invasive monitoring is necessary to
      precisely define the adequacy of the cardiac response and to individually tailor
      therapy. Patients who do not optimize and clear their lactate within 24 hrs may
      not survive.

PMID- 8143474
TI  - Skeletal muscle partial pressure of oxygen in patients with sepsis.
AB  - OBJECTIVE: In order to obtain direct evidence for tissue hypoxia in patients with
      sepsis oxygen, partial pressure was measured within skeletal muscle. Furthermore,
      serial intermittent and continuous measurements of skeletal muscle PO2 in
      patients with sepsis were used to find out whether skeletal muscle oxygenation
      may change in the course of sepsis and depends on the severity of sepsis. DESIGN:
      Prospective study. SETTING: Intensive care unit of a university hospital.
      PATIENTS: Intensive care patients (n = 98) with sepsis (group 1, n = 39; group 4,
      n = 28), limited infection (group 2, n = 16), and cardiogenic shock (group 3, n =
      15). INTERVENTIONS: Pulmonary artery catheterization; standard antibiotic therapy
      and volume replacement. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle PO2 was
      determined by polarographic needle electrodes or catheter probes. In patients
      with sepsis (n = 67), no evidence for skeletal muscle hypoxia was obtained from
      the PO2 distribution within biceps muscle. Mean skeletal muscle PO2 was increased
      in patients with sepsis (group 1, 48 torr [6.4 kPa]) compared with patients with
      limited infection (group 2, 28 torr [3.7 kPa]), p < .001) and with patients with
      cardiogenic shock (group 3, 22 torr [2.9 kPa], p < .001). Serial measurements of
      the PO2 distribution during seven consecutive days in another 28 patients (group
      4) with sepsis showed that a more severe degree of sepsis was associated with an
      increase of mean skeletal muscle (p < .001). These results were confirmed by
      continuous measurements of mean skeletal muscle PO2, using PO2 catheters.
      CONCLUSIONS: In patients with sepsis, oxygen transport to skeletal muscle was not
      critically reduced. Serial intermittent and continuous measurements of skeletal
      muscle PO2 showed that skeletal muscle PO2 increased in relation to the severity
      of the stage of sepsis. Our findings suggest that oxygen utilization within
      skeletal muscle decreased with deterioration of sepsis, thereby increasing
      skeletal muscle PO2.

PMID- 8143475
TI  - Closed versus open endotracheal suctioning: costs and physiologic consequences.
AB  - OBJECTIVE: To examine the physiologic consequences and costs associated with two
      methods of endotracheal suctioning: closed vs. open. DESIGN: A prospective,
      randomized, controlled study. SETTING: An eight-bed trauma intensive care unit
      (ICU) in a 460-bed level I trauma center. PATIENTS: The study included 35
      trauma/general surgery patients (16 in the open suction group, 19 in the closed
      suction group) who were treated with a total of 276 suctioning procedures (127
      open, 149 closed). MEASUREMENTS AND MAIN RESULTS: Physiologic data collected
      after hyperoxygenation, immediately after suctioning, and 30 secs after
      suctioning, were compared with baseline values. Open endotracheal suctioning
      resulted in significant increases in mean arterial pressure throughout the
      suctioning procedure. Both methods resulted in increased mean heart rates.
      However, 30 secs after the procedure, the open-suction method was associated with
      a significantly higher mean heart rate than was the closed method. Closed
      suctioning was associated with significantly fewer dysrhythmias. Arterial oxygen
      saturation and systemic venous oxygen saturation decreased with open suctioning.
      In contrast, arterial oxygen saturation and systemic venous oxygen saturation
      increased with the closed suction method. There was no difference between the two
      methods in the occurrence of nosocomial pneumonia. Open endotracheal suctioning
      cost $1.88 more per patient per day and required more nursing time. CONCLUSIONS:
      The closed suction method resulted in significantly fewer physiologic
      disturbances. Closed suctioning appears to be an effective and cost-efficient
      method of endotracheal suctioning that is associated with fewer suction-induced
      complications.

PMID- 8143476
TI  - Inflammatory markers: superior predictors of adverse outcome in blunt trauma
      patients?
AB  - OBJECTIVE: To assess whether variables reflective of early metabolic responses to
      injury are predictors of outcome in critically ill trauma patients. DESIGN:
      Clinical inception cohort study comparing conventional measures of injury
      severity with early host response markers for the correlation of each with
      outcome. These data are prospectively collected in a group of patients being
      evaluated in a nutritional support investigation. SETTING: Intensive care unit
      (ICU) of a major Level I trauma center. PATIENTS: Seventeen blunt trauma
      patients, aged 18 to 60 yrs with an Injury Severity Score of > or = 15, requiring
      early mechanical ventilation. INTERVENTIONS: Blood and urine samples were
      routinely obtained from patients undergoing nutritional support by one of three
      routes. MEASUREMENTS AND MAIN RESULTS: Conventional assessment was consistent
      with moderate severity and variation: Injury Severity Score, 41 +/- 15; Glasgow
      Coma Score, 11 +/- 4; admission circulating lactate concentration, 4.8 +/- 2.2
      mmol/L; and first 24-hr transfusion requirement, 3.1 +/- 2.9 L. The mean
      concentrations of inflammatory marker during the first week were: cholesterol,
      2.67 +/- 0.80 mmol/L (103.2 +/- 31 mg/dL); C-reactive protein, 23 +/- 11 mg/dL;
      transferrin, 1.44 +/- 0.47 g/L; glucose, 9.21 +/- 2.27 mmol/L (166 +/- 41 mg/dL);
      albumin, 26 +/- 5 g/L; and nitrogen loss, 24 +/- 9 g/d. Hospital outcome
      variables were: ventilator days, 17 +/- 7; ICU days, 26 +/- 10; hospital days, 38
      +/- 15; occurrence rate of adult respiratory distress syndrome (ARDS), 35%;
      infections, 82%; multiple organ failure, 71%; and total of hospital plus
      professional charges, $125,000 +/- $56,000. A significant (p < .05), but weak,
      correlation existed between all seven outcome variables and the inflammatory
      markers: ventilator days with cholesterol and C-reactive protein; ICU days with
      transferrin; total stay with cholesterol; ARDS with C-reactive protein;
      infections with glucose, cholesterol, and nitrogen loss; multiple organ failure
      with albumin and C-reactive protein; and financial charges with glucose. However,
      a significant correlation existed between only two of seven outcome variables and
      conventional measures of severity: multiple organ failure with lactate and
      financial charges with transfusion requirement. CONCLUSION: Readily obtainable
      inflammatory marker measurements may better reflect the summation effects of the
      early perfusion deficit and tissue injury in the blunt trauma patient compared
      with conventional measures of injury severity.

PMID- 8143477
TI  - Circulating interleukin-8 concentrations in patients with multiple organ failure
      of septic and nonseptic origin.
AB  - OBJECTIVES: Interleukin (IL)-8, a pro-inflammatory cytokine, is a potent
      chemoattractant factor and an activator of neutrophils produced by many cell
      types after stimulation by IL-1, tumor necrosis factor (TNF), or microbial
      products such as endotoxins. We investigated whether the presence of measurable
      IL-8 in plasma was associated with the clinical status of severely ill septic or
      nonseptic patients susceptible to the development of multiple organ failure.
      DESIGN: Cohort study. SETTING: A collaborative study between an intensive care
      unit and a research laboratory. SUBJECTS: Circulating IL-8 concentrations were
      measured in the plasma of 27 patients with sepsis syndrome and in 16 patients
      with noninfectious shock because these two conditions put patients at risk for
      the development of multiple organ failure. Sixteen of 27 patients with severe
      infection and 13 of 16 patients with noninfectious pathologies developed multiple
      organ failure. MEASUREMENTS AND MAIN RESULTS: A specific enzyme-linked
      immunosorbent assay (ELISA) for IL-8 was set up with a monoclonal and a rabbit
      polyclonal antihuman IL-8 using a sandwich technique. High concentrations of
      circulating IL-8 were found in the plasma of patients with sepsis syndrome. Among
      septic patients, a significant difference was observed between concentrations of
      IL-8 in survivors (n = 16) and nonsurvivors (n = 11) (81 +/- 13 pg/mL vs. 3326 +/
      1219 pg/mL, respectively; p = .001). A correlation was noticed between plasma IL
      8 and IL-6 concentrations (r2 = .42; p = .001), while no correlation was observed
      between IL-8 and TNF-alpha values, or between IL-8 and IL-1 beta. Although the
      mortality rate of nonseptic, multiple organ failure patients was 92%, low plasma
      concentrations of IL-8 were found (78 +/- 34 pg/mL), while high plasma
      concentrations were measured in septic, multiple organ failure patients
      (mortality rate 69%) who were sampled at a similar stage. By contrast, increased
      IL-6 values were observed in both septic and nonseptic, multiple organ failure
      patients. CONCLUSIONS: In septic patients, high amounts of circulating IL-8
      concentrations correlate with fatal outcome, whereas only low plasma
      concentrations of IL-8 are present in patients with nonseptic, multiple organ
      failure. This finding suggests that the signals involved in the exacerbation of
      IL-8 production are different, depending on infectious or noninfectious etiology.

PMID- 8143479
TI  - Bacterial translocation in burned mice after administration of various diets
      including fiber- and glutamine-enriched enteral formulas.
AB  - OBJECTIVE: Severe burn injury can produce acute gastrointestinal derangements
      which may facilitate bacterial translocation to mesenteric lymph nodes. We
      studied the effects of feeding different dietary formulations on bacterial
      translocation in burned mice. DESIGN: Prospective, blinded, nonrandomized
      laboratory study. SETTING: Research laboratory. SUBJECTS: One hundred sixty-nine
      female, outbred, CF-1 mice, 8 to 12 wks of age. INTERVENTIONS: Anesthetized mice
      received a 32% total body surface area, full-thickness burn injury. Mice were
      then fed with: a) mouse chow; b) a low-residue enteral formula; c) a high
      protein, high-fat enteral formula; d) an enteral formula with high concentrations
      of supplemental glutamine; or e) an enteral formula that contains soy fiber.
      MEASUREMENTS AND MAIN RESULTS: Burned mice that were fed the low-residue enteral
      formula demonstrated increased mortality rate (21.2%, p = .05) compared with chow
      fed mice in the 2-day postburn period (0 mortality); other burn-diet groups had
      intermediate mortality rates. In surviving mice, bacterial translocation was
      found to be: a) lowest in the group fed chow (31.0%) and the high glutamine
      formula (30.8%); b) intermediate in the group fed formula and soy fiber (44.8%,
      NS compared with burn-chow group); and c) highest in the group receiving the low
      residue enteral formula (73.1%, p < .005) and high-protein, high-fat enteral
      formula (59.3%, p < .05). CONCLUSIONS: Dietary composition markedly affects
      bacterial translocation in this animal burn model. Commercial enteral diets
      containing fiber and high concentrations of glutamine provide protection for the
      gut after burn injury and reduce the occurrence of bacterial translocation in
      this animal model.

PMID- 8143478
TI  - A perfluorochemical emulsion for prehospital resuscitation of experimental
      hemorrhagic shock: a prospective, randomized, controlled study.
AB  - OBJECTIVE: To evaluate the efficacy of a novel, oxygen-transporting
      perfluorochemical emulsion as a prehospital therapy, using a canine hemorrhagic
      shock model based on compromised tissue oxygenation. DESIGN: Prospective,
      randomized, controlled study. SETTING: HemaGen animal laboratory. SUBJECTS:
      Sixteen healthy, adult male grade beagles (weight 8 to 14 kg). INTERVENTIONS:
      Administration of lactated Ringer's solution (n = 8), 15 mL/kg and
      perfluorochemical emulsion admixed with physiologic salts (n = 8), 15 mL/kg.
      MEASUREMENTS AND MAIN RESULTS: PaO2 increased significantly (p < .01) in the
      perfluorochemical-treated animals for 2 hrs after resuscitation. Mixed venous PO2
      returned to preshock values in the perfluorochemical-treated dogs for 60 mins
      after fluid administration (p < .01). Normalization of hemodynamic variables was
      not observed in either group. Although not statistically significant, survival of
      the lactated Ringer's solution-treated animals was 63% compared with 100% for the
      perfluorochemical-treated dogs at 3 hrs after resuscitation. CONCLUSIONS:
      Resuscitation with a perfluorochemical emulsion augmented oxygen transport and
      restored global tissue oxygenation after massive hemorrhage, which translated
      into improved survival when compared with the group receiving an equal volume of
      lactated Ringer's solution.

PMID- 8143480
TI  - Effect of calcium to reverse the electrocardiographic effects of hyperkalemia in
      the isolated rat heart: a prospective, dose-response study.
AB  - OBJECTIVES: To determine: a) any heart site or tissue-specific differences in the
      response to increased perfusion potassium concentrations, and b) the cellular
      site (intracellular vs. extracellular) of the effect of calcium on reversing
      electrocardiographic effects of hyperkalemia. DESIGN: In vitro prospective,
      repeated-measures, dose-response study. SETTING: University/medical school
      experimental physiology laboratory. SUBJECTS: Adult male Sprague-Dawley rats
      whose hearts were studied in an in vitro perfusion preparation. INTERVENTIONS:
      One group of hearts was perfused with modified Krebs-Henseleit physiologic salt
      solution onto which were superimposed infusions of concentrated potassium and/or
      calcium solutions. Infusion rates increased stepwise the respective ions in order
      to calculate increased concentrations through the course of the experiment.
      Calcium concentration was at either 4.0 or 5.4 mEq/L (2.0 or 2.7 mmol/L);
      potassium concentration was increased from 5.8 to 7.3, 8.0, 8.8, 10.2 and 11.8
      mmol/L. Two more groups of hearts were perfused with Krebs-Henseleit solution
      containing the lower calcium concentration to which was added the calcium
      ionophore A23187 in one of two doses. A fourth group of hearts was perfused with
      Krebs-Henseleit solution containing the higher calcium concentration to which was
      added the a single dose of the calcium-channel blocking agent verapamil.
      MEASUREMENTS AND MAIN RESULTS: We tested the effects of a series of ion and drug
      concentrations on epicardial EKG variables (atrial and ventricular rates, P-wave
      amplitude, PR interval, QRS complex amplitude and duration, and T-wave amplitude
      and duration). The effects of these variables were tested by increasing the
      ionized calcium in the perfusate of isolated rat hearts from 4.0 mEq/L (2.0
      mmol/L) to 5.4 mEq/L (2.7 mmol/L) as perfusate potassium was increased stepwise
      from normal (5.8 mEq/L or mmol/L) to as high as 11.8 mEq/L (mmol/L). In addition,
      we studied the effect of adding the calcium ionophore A23187 to the perfusate
      with the lower ionized calcium concentration, and we also studied the effect of
      adding the calcium-channel blocking agent verapamil to the perfusate containing
      the higher ionized calcium while increasing the perfusate potassium concentration
      in a stepwise manner in each of the series. The higher calcium concentration (5.4
      mEq/L or 2.7 mmol/L) prevented most of the adverse effects of the highest
      potassium concentration in the first drug-free series of experiments. When the
      calcium ionophore A23187 was added to the perfusate, most electrocardiographic
      variables remained normal even in the presence of a lower ionized calcium
      concentration. However, the higher ionized calcium concentration was not able to
      prevent electrical abnormalities in hearts perfused with high potassium when
      verapamil was in the solution. CONCLUSIONS: We conclude that the mechanism
      whereby calcium reverses the clinically observable electrocardiographic effects
      of hyperkalemia is an intracellular one.

PMID- 8143481
TI  - Improvised automatic lung ventilation for unanticipated emergencies.
AB  - OBJECTIVES: To design an improvised circuit that can be used to extend the
      capability of a single ventilator to ventilate two or more patients and that can
      be assembled from readily available parts in times of unanticipated emergency.
      DESIGN: Research and development, followed by technical analysis and evaluation.
      SETTING: Biomedical laboratory. MEASUREMENTS AND MAIN RESULTS: We describe two
      circuits that can be assembled from readily available inexpensive components to
      function as improvised ventilators. One circuit requires only a central mushroom
      valve driver and an additional source of fresh gas for each patient. The other
      circuit is configured as a number of secondary circuits in parallel, connected to
      a single ventilator. We constructed and tested the circuits using mechanical lung
      simulators. The secondary circuit configuration was more efficient in terms of
      fresh gas usage, but was more complex regarding operation and trouble-shooting.
      CONCLUSIONS: These two improvised circuits can extend the capability of a
      standard volume-cycled ventilator to provide automatic ventilation of the lungs
      in times of disaster.

PMID- 8143482
TI  - Disadvantages of prolonged propofol sedation in the critical care unit.

PMID- 8143483
TI  - Successful treatment of Candida prosthetic valve endocarditis with a combination
      of fluconazole and amphotericin B.

PMID- 8143484
TI  - Removal of cytokines in septic patients using continuous veno-venous
      hemodiafiltration.

PMID- 8143485
TI  - Removal of cytokines in septic patients using continuous veno-venous
      hemodiafiltration.

PMID- 8143486
TI  - Removal of cytokines in septic patients using continuous veno-venous
      hemodiafiltration.

PMID- 8143487
TI  - Removal of cytokines in septic patients using continuous veno-venous
      hemodiafiltration.

PMID- 8143488
TI  - Knowledge-based protein modeling.
AB  - Knowledge, both from the three-dimensional structures of homologous proteins and
      from the general analysis of protein structure, is of value in modeling a protein
      of known sequence but unknown structure. While many models are still constructed
      at least in part by manual methods on graphics devices, automated procedures have
      come into greater use. These procedures include those that assemble fragments of
      structure from other known structures and those that derive coordinates for the
      model from the satisfaction of restraints placed on atomic positions.

PMID- 8143489
TI  - Cutaneous melanoma: current practice and surgical controversies.

PMID- 8143490
TI  - Temporary arterial occlusion during intracranial aneurysm surgery.
AB  - Temporary arterial occlusion during intracranial aneurysm surgery is a safe and
      effective modality. It is not only an emergency measure for controlling
      aneurysmal bleeding, but also a helpful means for accurate and meticulous
      dissection and clipping of an intracranial aneurysm with the advantage of
      minimizing the chance of its premature rupture or causing damage to the vital
      neurovascular structures. This technique is especially useful for treating large
      or giant aneurysms, carotid-ophthalmic arterial aneurysms, or thin-walled and
      complicated aneurysms tightly adherent to their surrounding tissues. A series of
      52 patients with temporary clipping of the involved arteries during intracranial
      aneurysm surgery were reviewed retrospectively, which represented 37.1% of all
      aneurysms operated on in Huashan Hospital, Shanghai Medical University during the
      same period (from 1980 to 1990). Of them, one died (1.9%), 10(19.2%) had
      immediate or early neurological deficits which were mostly resolved later. A
      follow-up study with an average time of 3.8 years showed that 98% of patients had
      an excellent and good recovery without significant deficits. Comparing these
      results with those in 88 patients with aneurysms operated on over the same period
      in which temporary clips were not used, there is clearly no significant
      difference. The use of brain protectors, barbiturates, hypothermia and some
      monitoring systems can increase the safe coefficient to the brain and reduce the
      occurrence of ischemic complications during the application of temporary arterial
      occlusion. However, there is so far neither an absolute reliable medication or
      monitor, nor a well accepted safe time-limits to vascular occlusion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143491
TI  - Classification of pulse waveform of cerebral spinal fluid during intracranial
      pressure monitoring.
AB  - Cerebral spinal fluid (CSF) pulse waveform basing on 899 records was classified.
      Eleven types of CSF pulse waveform were further classified according to the
      harmonic wave relation and the configuration of the pulse waveform. The
      characteristic features of various types of CSF pulse waveform were considered to
      reflect certain intracranial pathophysiological conditions including cerebral
      compliance, cerebral vasomotor reactivity and intracranial elastance.

PMID- 8143492
TI  - Experimental and clinical studies on one-stage arterialization of the venous
      channels for revascularization of severely ischemic limbs.
AB  - A new approach to perfuse arterial blood through venous channels for
      revascularization of severely ischemic limbs is reported. The procedure studied
      and used consists of creating an arteriovenous fistula between the normal
      arterial trunk proximal to the occlusion and the deep venous trunk of the
      diseased limb, constricting the venous trunk proximal to the anastomosis to one
      third of its lumen diameter, ligating the communicating and small tributary veins
      distal to the constriction in the operative field. The results of the
      experimental and clinical studies have shown that the treated ischemic limb was
      quickly revascularized without undesirable influence on cardiac function. This
      new approach has been used in the treatment of severe ischemia involving total
      212 limbs in 156 patients, and the results appeared more satisfactory than those
      treated with staged arteriovenous reversal.

PMID- 8143493
TI  - Anti-CD3 and -CD4 monoclonal antibody in the treatment of steroid-resistant renal
      allograft rejection.
AB  - Between November 1987 and October 1991, 40 consecutive cadaveric renal recipients
      immunosuppressed with cyclosporine (CsA) who developed renal allograft rejection
      were treated with domestically prepared muromonab CD3 (Wu 338) and CD4 (Wu167).
      CD3 and CD4 monoclonal antibodies (McAb) as rescue treatment (n = 34)
      successfully reversed 29 cases of (85.3%) intractable renal allograft rejection
      (steroid resistant rejection 32 and anti-human thymocyte globulin [AHTG]
      resistant rejection 2) and completely reversed 4 cases of acute renal rejection
      episodes CD3 McAb as first-line treatment (n = 4). Two cases of chronic rejection
      failed in the treatment of McAb. Rejection episodes were reversed from 4 to 11
      days (mean 6 days). Combined use of CD3 and CD4 McAb seemed to yield better
      results. Peripheral blood T lymphocyte subsets showed that CD3+, CD4+ and CD8+
      decreased significantly after the treatment of McAb. No severe side-effects were
      observed in the treatment of McAb. The McAb could be administered safely.
      Pulmonary infection rate was 15%. The yearly graft survival rate was increased
      significantly (87.8% vs 80.0%).

PMID- 8143494
TI  - Effects of osteogenesis on dermal fibroblasts cultured in vitro.
AB  - Fibroblast were harvested from in vitro culture of split-thickness skin of New
      Zealand rabbit. Some opaque bone nodules were found in the culture flasks when
      the fibroblasts underwent subculture for 8 days. After a 37-day subculture of
      fibroblasts, some of the nodules might enlarge extend and form trabecular-like or
      flake-like structures. The above-mentioned structures revealed golden-yellow
      fluorescence under the blueviolet light fluorescence microscope when the
      specimens were labeled with tetracycline intravitally, denoting that they were
      newly formed bone tissues. Both calcium salt and collagen stainings for these
      structures showed positive reaction, fully reflecting the calcium and collagen
      composition. Osteogenesis caused by dermal fibroblast cultured in vitro was thus
      verified.

PMID- 8143495
TI  - Immunohistochemical and histological studies on internal derangement and organic
      disturbance of temporomandibular joint.
AB  - The study examined the articular cartilages of 14 patients who suffered from
      temporomandibular joint disturbance syndrome (TMJDS) and 3 healthy fresh cadavers
      by light microscopy and immunofluorescence, and assayed 14 patients' synovial
      fluids and sera with indirect hemoagglutination. The results showed that there
      were antibodies to type II collagen in synovial fluids in 5 of 14 patients and
      there were some immune complexes in cartilage. So, the authors think that there
      are autoimmune reactions in the articular tissues in TMJDS because of the
      exposure of some sequestered antigens.

PMID- 8143496
TI  - Recurrent parotitis in adults. Report of 35 cases.
AB  - Clinical, laboratory and sialographic findings were studied in 35 adult patients
      with recurrent parotitis. The patients were followed up for 0.5-23 years. The
      results showed that sialographic recovery occurred 3-5 years after disappearance
      of clinical symptoms. Recurrent parotitis is not a autoimmune disease, and
      remission may take place spontaneously, including clinical and sialographic
      healing. However, marked degeneration of the parotid gland or chronic obstructive
      parotitis may develop consequently. The differential diagnosis of recurrent
      parotitis in adults is also discussed.

PMID- 8143497
TI  - Guillain-Barre syndrome and Campylobacter jejuni infection. A study on the
      etiological characteristics of Guillain-Barre syndrome in China.
AB  - Fecal culture for Campylobacter jejuni with the method of Skirrow and serum class
      specific antibodies (IgG, IgM, IgA) against Campylobacter jejuni using a solid
      phase enzyme linked immunosorbent assay were performed in 17 cases of Guillain
      Barre Syndrome, 17 other neurological disease controls, and 33 normal controls.
      The results revealed: 1. the incidence of Campylobacter jejuni infection,
      especially the recent one in Guillain-Barre Syndrome was much higher than in the
      other two groups; 2. the recent incidence of infection in those below 30 years
      old and those within the period of summer and autumn was higher than that above
      30 years old and that in the other seasons. The results suggested that
      Campylobacter jejuni infection might be one of the important precipitating
      factors of Guillain-Barre syndrome and might play an important role in the
      epidemiological pattern of Guillain-Barre Syndrome in China.

PMID- 8143498
TI  - Study on cytomegaloviral infection in acute leukemia patients by polymerase chain
      reaction.
AB  - Polymerase chain reaction (PCR) and blot hybridization by probe labelled with
      digoxin were used to detect human cytomegalovirus (HCMV) DNA in 31 patients with
      acute leukemia and 20 controls. The positive rate detected by PCR in acute
      leukemia was 74.2% and 15.0% in the controls. The difference was statistically
      significant. The results suggest that acute leukemia patients are the high risk
      population with high infection rate of HCMV. The positive rate detected by
      digoxin method in acute leukemia was 58.1%. Six patients showed negative results
      by digoxin method, but positive by PCR. It was demonstrated that PCR was superior
      to digoxin method in sensitivity. Anti-HCMV IgM in serum of patients was detected
      at the same time, the positive rate was 16.1%. Only 6 of the 23 PCR positive
      patients showed positive anti-HCMV IgM. It suggests that the immune response is
      weak in acute leukemia patients and HCMV recently infected could not be excluded
      in the anti-HCMV IgM negative cases.

PMID- 8143499
TI  - Combined endovascular embolization of large intracranial arteriovenous
      malformations and their subsequent surgical resection.
AB  - Twelve patients with large arteriovenous malformations (AVMs) were subjected to
      endovascular embolization followed by surgery. Of the 12 patients, 9 were males
      and 3 females. Their age ranged from 11 to 37 years. Eleven AVM nidi were more
      than 6 cm in diameter and one AVM, located in a crucial brain area, was 4 cm in
      diameter. More than 70% of the AVM masses were excised in 11 of the patients,
      while under 50% was excised in the remaining patient. Complete excisions of the
      lesions were achieved in all 12 patients 7-10 days after endovascular
      embolization. No new major neurological deficits occurred. The results showed
      that the cerebral AVMs can be effectively operated on after endovascular
      embolization.

PMID- 8143500
TI  - Double-valve replacement in a case of isolated dextrocardia and corrected
      transposition of great arteries.

PMID- 8143501
TI  - Systemic fibrous dysplasia involving multiple bones in human body. Report of 4
      cases.
AB  - Four cases of systemic fibrous dysplasia were selected from 356 cases of fibrous
      dysplasia. All of them were verified pathologically. In these 4 cases, the long,
      short, flat and irregular bones were involved. Some of the changes were
      characteristic in comparison with those of the monostotics or regional types.
      This disorder was often seen clinically in females, started in early childhood
      and exacerbated during puberty. Its main symptoms were primary or secondary
      deformities. Radiologically, the main changes were diffuse and uniform expansion
      and developmental disturbances of the bones and joints.

PMID- 8143502
TI  - Combination chemotherapy with DATV regimen in treatment of adult acute
      nonlymphocytic leukemia.

PMID- 8143503
TI  - Computer assisted analysis of leukocyte rheological behavior in microvasculature.
AB  - A new approach called Time-Space Scheme has been recommended for measuring the
      velocity of moving blood cells in the microvasculature. In each sampling time,
      the data are put into a row, then rows are integrated in sequential times as
      sequential rows. The motion of various objects in the field of microcirculation
      can be analyzed from the time-space image. In the time-space image RBC's flow
      appears as a diagonal dark stripe and WBC's flow as a bright stripe. The slope at
      different points on those stripes reflects the local velocity of RBCs and WBCs.
      Using the time-space image analyzing method, the velocities of erythrocyte and
      leukocyte in microcirculation are measured simultaneously by a self-designed
      interactive image processing system. According to characteristic of leukocyte
      flowing movement, leukocytes in microvasculature are divided into the three
      kinds: central axial-flowing leukocyte, rolling leukocyte and adhesive leukocyte.
      On this basis, we introduce the leukocyte-endothelium contact time as a
      quantitative index for leukocyte-endothelium interaction. During hemorrhagic
      shock, the phenomenon of leukocyte-endothelium adhesion has been observed by this
      system, which suggests that the method is effective and useful for the research
      of microcirculation.

PMID- 8143504
TI  - Gene expression of Na+/Ca2+ exchanger in brain ischemia.
AB  - It is known that intracellular Ca2+ is overloaded during ischemia as a result of
      the altered activity of the Na+/Ca2+ exchanger, one of the major pathways of Ca2+
      efflux. But the molecular mechanism of the alteration is still unknown. We cloned
      a -500bp cDNA fragment of rat cerebellar Na+/Ca2+ exchanger gene. Using this cDNA
      fragment as the probe, we found that the Na+/Ca2+ exchanger mRNA is widely
      distributed in rat central and peripheral nervous system such as in cerebra,
      heart, lung and kidney. Using focal cerebral ischemic model, we detected the gene
      expression of Na+/Ca2+ exchanger in ischemic brain by Northern bolt and in situ
      hybridization, and found that in ischemic tissues, the mRNA level of Na+/Ca2+
      exchanger is lowered.

PMID- 8143505
TI  - Expression levels of IL-6 mRNA in PBMNCs from patients with IDDM, NIDDM and
      normals by RT-PCR procedure.
AB  - Although it has been confirmed that insulin dependent diabetes mellitus (IDDM) is
      a kind of autoimmune disease, islet cell autoantibodies (ICAs), insulin
      autoantibodies (IAA) and anti-GAD-glutamic acid decardaxylase antibodies have
      been found in the sera of patients with IDDM and immunotherapies have been used
      in some patients with IDDM, yet the manner in which the dysfunctional
      immunosystem acts on beta cells and causes damage to them remains to be
      clarified. Recently, possible involvement of the abnormal production of IL-6 in
      autoimmune symptoms was suggested in patients with cardiac myxomas, Castleman's
      disease and rheumatoid arthritis. However reports of IL-6 abnormal production in
      patients with IDDM are rare. In the present study, we examined whether or not an
      abnormal expression of IL-6 mRNA was present in mononuclear cells (PBMNCs) of the
      peripheral blood of patients with IDDM. We devised a highly sensitive, specific
      and semiquantitative protocol, ie, reverse transcription and polymerase chain
      reaction (RT-PCR). We have used such an assay to measure the relative expression
      levels of IL-6 mRNA in PBMNCs from 12 early IDDM patients (duration < 6 mon, 8.20
      +/- 3.85 yr), 29 newly-diagnosed NIDDM patients (54.85 +/- 9.12 yr), 23 normal
      children (8.20 +/- 3.26 yr) and 12 normal adults (31.92 +/- 11.22 yr). In this
      assay significantly high expression levels of IL-6 mRNA were found in PBMNCs from
      patients with IDDM (P < 0.05). The relative levels were 0.91 +/- 0.19; 0.10 +/-
      0.06; 0.43 +/- 0.08; 0.10 +/- 0.07, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8143506
TI  - Contribution of differences in plasma binding of propranolol to ethnic
      differences in sensitivity. Comparison between Chinese and Caucasians.
AB  - Chinese are more sensitive to the beta-blocking and hypotensive effects of
      propranolol than Caucasians. To determine the contribution of ethnic differences
      in the plasma binding of propranolol to the differences in sensitivity, 8
      Caucasians (22.8 +/- 1.5 yr) and 8 Chinese (31.8 +/- 2.1 yr) were studied
      following single doses of 0, 10, 20, 40 and 80 mg propranolol orally. The binding
      of propranolol in plasma was determined by equilibrium dialysis after addition of
      300 mg racemic propranolol to the plasma. The concentrations of free and bound
      (+) and (-)-propranolol were determined by stereospecific high performance liquid
      chromatography (HPLC). Dosage had no influence on the plasma binding of either
      enantiomer. The unbound fractions of both (-)-propranolol (16.06 +/- 0.79% vs
      12.41 +/- 0.93%, P < 0.05) and (+)-propranolol (17.73 +/- 0.81% vs 14.33 +/-
      0.89%, P < 0.01) were greater in Chinese than Caucasians, respectively. In both
      groups, the ratio of unbound (-) to (+)-propranolol was less than 1 (P < 0.01)
      and was greater in Chinese (0.91 +/- 0.01 vs 0.88 +/- 0.01) (P < 0.01), implying
      that in Chinese less isomers of both types were bound and there was a greater
      unbound proportion of the pharmacologically active (-)-propranolol which may
      contribute to their increased sensitivity to propranolol. It is demonstrated that
      ethnic differences in stereoselective protein binding may be an important
      variable in interindividual determinants of drug response.

PMID- 8143507
TI  - Effect of captopril cardioplegia on renin-angiotensin system, prostaglandins,
      free radicals and electrolytes in the isolated hypothermic ischemic and
      reperfusion rabbit hearts.
AB  - The effect of captopril cardioplegia on ischemic and reperfusion myocardium after
      3 hours of hypothermic (13 +/- 1 C) arrest and 35 minutes of reperfusion was
      studied in the isolated working rabbit heart. In comparison with the control
      group, captopril cardioplegia reduced the content of angiotensin II (381 +/- 56
      vs 507 +/- 84 pg/g wt of the control group, P < 0.01) and MDA (50.0 +/- 9.2 vs
      85.1 +/- 16.1 pmol/mg pr, P < 0.01) in the reperfusion myocardium; augmented the
      renin activity of ischemic (1050 +/- 353 vs 669 +/- 301 pg/g wt/h, P < 0.05) and
      reperfusion myocardium (1261 +/- 421 vs 498 +/- 353 pg/g wt/h, P < 0.01)
      increased the 6-K-PGF1 alpha/TXB2 ratio in the reperfusion myocardium (by 48.1%
      of the control group). Meanwhile, captopril cardioplegia could also decrease the
      content of calcium (0.027 +/- 0.015 vs 0.045 +/- 0.014 microM/mg pr, P < 0.05)
      and sodium (0.54 +/- 0.26 vs 0.82 +/- 0.15 microM/mg pr, P < 0.05) in the
      reperfusion myocardium, but had no effect on the potassium content. The results
      show that the protective effect of captopril on hypothermic myocardium may be
      related to the free radical scavenging action, inhibition of angiotensin II
      production, improvement of PGI2/TXA2 ratio and decrease of calcium and sodium
      overload in the myocardium.

PMID- 8143508
TI  - Homotransplantation of testis. A report of 11 cases.
AB  - Testis homotransplantation has been carried out in 11 patients since 1986. Of
      them, 8 suffered from congenital testicular dysplasia and the other 3 from
      orchiatrophy as a result of orchitis. Preoperatively, manifestations were a small
      penis, small testes, sexual dysfunction, indistinct secondary sex characteristics
      and low serum testosterone (1.7-7.35 mmol/L). Three cases had cadaver transplants
      and 8 had living relatives' transplants. The patients were followed up for 7
      months to 4 years. The secondary sex characteristics and sexual function were
      improved remarkably after transplantation. Serum testosterone increased up to
      12.8-18.2 mmol/L. All of 5 married patients resumed sexual intercourse
      satisfactorily. Three others got married after transplantation and have enjoyed
      normal sexual functions. Spermatozoa have been found in the semen in 3 of the
      cases.

PMID- 8143509
TI  - Increased plasma endothelin-1 concentration in patients with acute cerebral
      infarction and actions of endothelin-1 on pial arterioles of rat.
AB  - In acute cerebral ischemia there are severe damages of endothelium which have
      been recognized as the stimuli to secrete endothelin-1, an endothelium-derived
      peptide and the most potent vasoconstrictor ever known. This study was to measure
      plasma endothelin-1 level in patients with cerebral infarction and explore the
      relationship between endothelin-1 and ischemic stroke. The possible involvement
      of endothelin-1 in local regulation of cerebral arterioles was also investigated.
      Plasma levels of endothelin-1 were measured by radioimmunoassay in 21 patients.
      Using a micro-video system, the endothelin-1 actions were also observed on rat
      pial arterioles in vivo, and with incomplete cerebral ischemia model (rat),
      effect of ischemia affects the endothelin-1 action. There was a marked increase
      in plasma endothelin-1 level in the patients and the elevation persisted during
      the acute and subacute period of stroke. There was a positive correlation between
      the peptide concentration and infarct size (r = 0.655, P < 0.01). In rats,
      endothelin-1 (dose range: 10(-10) mole/L-10(-7) mole/L) induced a dose-dependent
      arteriole contraction after subdural administration. Arteriole calibers were
      decreased by 27.7% +/- 3.8% (10(-9) mole/L), 46.8% +/- 4.9% (10(-8) mole/L) and
      78.5% +/- 4.7% (10(-7) mole/L), respectively. Cerebral ischemia significantly
      enhanced the action of endothelin-1 (96.4% +/- 7.2% vs 58.2% +/- 6.8%).
      Endothelin-1 plays an important role in regulating local circulation of ischemic
      brain. The notable and lasting increase in plasma level of endothelin-1 are
      associated with cerebral ischemia and infarction.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8143510
TI  - Evidence of compromised circulation in the pathogenesis of optic nerve damage in
      chronic glaucomatous rabbit.
AB  - The protective effect of improving the microcirculation on the retinal ganglion
      cells (RGC) and the ultrastructure of the optic nerve after intravenous (i.v.)
      use of Salviae miltiorrhiza (SMR) was studied in a chronic intraocular
      hypertension model in 36 rabbits. These rabbits were treated with topical 0.5%
      timolol, or i.v. SMR or i.v. 0.9% saline for 1, 3, 5 or 8 weeks. The intraocular
      pressure (IOP) was 19.6 +/- 2 mmHg and the RGC density was 1140 +/- 121.2/mm2 in
      control rabbits. After one week of intraocular hypertension (IOP between 30 and
      40 mmHg), the RGC densities decreased to between 650 and 820/mm2. Following the
      use of timolol for 1 to 8 weeks, IOP returned to control level and the RGC
      density increased to 1015 +/- 7/mm2. After treatment with i.v. saline for 8
      weeks, the RGC density decreased progressively from 651 +/- 1/mm2 at the
      beginning of treatment to 83 +/- 3/mm2. The RGC density of those rabbits treated
      with i.v. SMR for 8 weeks remained virtually unchanged (658 +/- 5/mm2) compared
      to the RGC density at the beginning of the treatment. Severe ultrastructural
      damage of optic nerve and collapsed capillaries were found in rabbits treated
      with saline while these findings were mild in rabbits treated with SMR. During
      these periods of treatment, the intraocular hypertension did not decrease in
      rabbits treated with either saline or SMR. From these findings and the fact that
      SMR improves local microcirculation, it is considered that the compromised
      microcirculation is one of the mechanisms in the pathogenesis of optic nerve
      damage in chronic glaucoma.

PMID- 8143511
TI  - Syndrome of hypertension and hyperkalemia with normal GFR (Gordon's syndrome:
      pseudohypoaldosteronism type II).

PMID- 8143512
TI  - [An observation on the regularity of mould invasion into sugarcane and its
      prevention].
AB  - The factors that influence mould invasion into sugarcane were investigated.
      Results showed sales pattern, storage condition, and duration of storage for
      sugarcane were the major influential factors to its mildew. Antiseptic agents had
      no obvious protective effects on mould invasion. According to authors'
      experiments, sugarcane can be stored for no more than 3 weeks to prevent from
      mildew. The outward appearance of sugarcane changed with its contamination of 3
      NPA. A simple method for detecting mildew in sugarcane was also described in the
      paper.

PMID- 8143513
TI  - [The inhibitory effects of epicatechin complex on diethylnitrosamine induced
      initiation of hepatocarcinogenesis in rats].
AB  - The inhibitory effects of epicatechin complex (ECC) on diethylnitrosamine (DEN)
      initiation of carcinogenesis and influences of ECC on the phenotypic changes and
      the levels of oncogene N-ras expression were studied in rats model with multiple
      small dose DEN induced liver precancerous lesion. Results showed ECC can markedly
      inhibit DEN induced variant cell foci and nodes, particularly OCT altered and
      multiple enzyme altered foci and nodes. The dot blot hybridization of the total
      RNA extracted from liver tissue with 32P-labelled N-ras cDNA probe showed N-ras
      expression decreased more in ECC treated animals than that in untreated ones. N
      ras cDNA-mRNA in situ hybridization in liver sections indicated ECC can markedly
      inhibit the size of DEN induced variant cell foci and decrease the number of N
      ras over expression lesions. Histochemical study showed that the N-ras over
      expression foci were corresponding to the multiple enzyme and/or OCT altered
      lesions. The above results showed ECC can apparently inhibit DEN induced
      initiation of hepatocarcinogenesis in rats.

PMID- 8143514
TI  - [An analysis on the reported values of trace elements in human serum].
AB  - Statistical analysis on the data of trace element contents in human serum,
      published in the past 30 years, indicated the reported values for the majority of
      trace elements tended to decrease, even by magnitude of two orders, with the
      rapid development in analytical techniques and the effective control of
      contamination of samples during their collection, treatment and analysis. While
      the reported values approached their true ones, they would change to follow a
      normal distribution from a log normal one, with relative standard deviation and
      geometric deviation diminishing and, arithmetic mean approaching geometric mean.
      On the basis of the above results, the author presents the normal values, the
      best estimated normal values and the best literature values for Cu, Zn, Se, Co,
      Mo, Mn, Cr, Ni, As, Rb, Br, Cs, and Al.

PMID- 8143515
TI  - [Biological monitoring of workers exposed to nitrofen and experimental study on
      its skin permeability].
AB  - Eleven packing workers in a nitrofen manufacturer were selected in a three
      consecutive day field study, Skin contamination, urine excretion, and air
      concentration of nitrofen before and after workshift were monitored with GC-ECD
      method. Results showed air nitrofen concentrations in the workplace were
      extremely high, ranging from 5.12 to 21.60 mg/m3 (TWA). The hand and forehead in
      workers, who handled wettable nitrofen powder with bare hands, were contaminated
      by nitrofen with levels of 5.80 and 1.15 micrograms/cm2, respectively. Nitrofen
      excretion in urine increased after workshift and reached the highest in 10 hours,
      with a half excretion time of 13 hours. Permeability study with a flow-through
      diffusion cell in vitro showed nitrofen could easily penetrate human skin in
      different location of the body, and the permeability in forearm skin was stronger
      than that in thigh, and much more than that in abdomen skin. Nitrofen amount
      penetrated increased greatly as the skin barrier was damaged. Both the skin and
      respiratory absorption could be the important routes for nitrofen uptake. It was
      imperative to protect the skin from contamination while to strengthen respiratory
      protection. Results also suggested nitrofen level in urine could be used to
      indicate the body uptake through different routes.

PMID- 8143516
TI  - [The relationship between concentrations of B(a)P in blood, urine and immune
      function of coking workers].
AB  - The surroundings of a coking plant were contaminated with benzo(a)pyrene [B(a)P]
      in various degrees. B(a)P in urine and blood of the coking workers was detected,
      and levels of B(a)P in urine and blood showed correlated. Also, the relationship
      between the contents of B(a)P in urine and the surroundings of the plant was
      found. The levels of immunoglobulin (IgG, IgA, IgM) and complement C3 in serum of
      the coking workers decreased. The levels of IgG and C3 in the workers were
      significantly different from those in controls. And, the serum contents of B(a)P
      in the workers also correlated with their immune function.

PMID- 8143517
TI  - [VDT pulse magnetic field enhances teratogenic effect of ara-c in mice].
AB  - Impregnated NIH mice were irradiated 4 hrs daily on days 16th-17th of gestation
      with 15.6 kHz pulse magnetic field at 40 microT peak to peak. Significant
      enhancement of ara-c induced teratogenic potency by the magnetic field can be
      observed. The incidence of harelip fetuses bearing harelip and/or cleft palate
      was significantly higher in the combined exposure group, in which mice were
      exposed to the magnetic field and given an intraperitoneal injection of ara-c on
      the 9th day of gestation, than that of mice treated with ara-c alone.

PMID- 8143518
TI  - [Study on the relationship between dietary aflatoxin B1 levels in foods and
      aflatoxin M1 excretion levels in children's urine in Guangxi].
AB  - 617 children in high and low liver cancer incidence areas of Guangxi were
      observed for a study on the relationship between the dietary Aflatoxin B1 (AFB1)
      levels and Aflatoxin M1 (AFM1) excretion amounts in urine. The average amount of
      Aflatoxin B1 absorbed by children within 24 hours was 0.0883 x 10(-9) micrograms,
      (0.1232 x 10(-9)) in high liver cancer incidence area (LCIA), and 0.0306 x 10(-9)
      in low LCIA (P < 0.001). The average amount of AFM1 excreted in the children's
      urine within 24 hours was 0.0020 x 10(-9) micrograms, (0.0027 x 10(-9) in high
      LCIA, and 0.0010 x 10(-9) in low LCIA (P < 0.001). The conversion ratio from AFB1
      to AFM1 excreted from urine was 2.27% in 24 hours after the children consumed
      AFB1 from foods. The ratio of conversion was 2.19% and 3.27% for the children who
      life in high and low LCIA respectively, it was 1.75% for the boys, 2.97% for the
      girls.

PMID- 8143519
TI  - [Determination of acrylamide metabolite, mercapturic acid by high-performance
      liquid chromatography].
AB  - A high performance liquid chromatography (HPLC) Assay was developed to identify
      and measure the metabolite of acrylamide, mercapturic acid, N-Acetyl-s
      (propionamide) cysteine (APC) in urine. O-phthalaldehyde (OPA) was utilized as a
      pre-column derivative agent in the assay. This derivative was isolated with a
      good selectivity by ODS columns. The quantitation of the mercapturic acid
      derivative was reproducible and with a detection limit of 1 pmol. The average
      coefficient of variation for the runs carried out on the same day was
      approximately 4.6% at the range of 80-160 mumol/L of APC, and the mean analytical
      recovery from urine samples was 94%. The metabolite of urine of workers exposed
      to acrylamide was identified as APC by HPLC and fluorescence scan and HPLC-Mass
      spectra. All results were identical with the authentic synthesized compound.

PMID- 8143520
TI  - [Mercury concentration in fish taken from the second Songhua River and mercury
      intake by fish-consumers].
AB  - Dynamic changes of standardized mercury concentration in fish taken from the
      Second Songhua River were evaluated from 1973 to 1991. It decreased 82.6% during
      this period. And, mercury intake of fish-consuming population and its source were
      studied. The results proved mercury concentration accumulated in some of the high
      risk population in 70's came up to and exceeded the threshold for chronic
      methylmercury poisoning. But, since 1983 mercury level in human body has been
      dropping greatly, and now falls down below the safety limit. The above facts
      showed mercury contamination in the Second Songhua River has been under control.
      But, fish intake should be still limited to appropriate amount to prevent from
      risk of poisoning.

PMID- 8143521
TI  - [Pseudomonas contamination of Chinese herbal drug. Tremella fuciformis].

PMID- 8143522
TI  - [Analysis of familial aggregation of lung cancer in Xuanwei].
AB  - Lung cancer aggregation was analyzed in relatives of the proband compared with
      those of his/her spouse in 370 nuclear families. Results showed the relatives of
      the proband had a greater risk of lung cancer compared with those of his/her
      spouse with an OR of 1.85 (P < 0.01). Even more, female relatives of the proband
      had much greater risk of lung cancer than those of his/her spouse with and OR of
      2.64 (P < 0.01). It suggested relatives of the proband are more vulnerable to
      lung cancer than those of his/her spouse and genetic factor may contribute to
      pathogenesis of lung cancer.

PMID- 8143523
TI  - [Effects of purified VLDL injection on experimental hyperlipidaemia].
AB  - Forty-two neonate NZW rabbits were randomly allocated to two experimental groups
      (II and III) and a control group (I). Groups II and III were intraperitoneally
      injected with purified VLDL 0.5mg and 1.0mg, respectively within 12 hours after
      their birth, and then were repeated with same doses twice on the 7th and 15th
      day, respectively. From the 18th day of their life, all the rabbits were fed with
      high cholesterol forage to establish atherosclerosis models. Serum levels of TG,
      TCh, and HDL-C were determined in the 17th, 30th, and 40th week of their life.
      Serum levels of TG in Groups II and III were much lower than those in Group I in
      the 17th week. Serum levels of TG and ratio of LDL-C to HDL-C were significantly
      lower and of HDL-C much higher in Groups II and III than those in Group I in the
      30th week. The results determined in the 40th week were the same as above, and
      serum levels of TCh in Groups II and III were significantly lower than those in
      Group I. There Were no significant differences in serum levels of LDL-C and TCh
      among the three groups. The results suggested peritoneal injection of purified
      VLDL into rabbits in their earliest stage of life had effects on the formation of
      hyperlipidaemia, and could Prevent them from atherosclerosis. Its mechanism was
      briefly discussed in the paper.

PMID- 8143524
TI  - [Influence of smoking on red cell immune functions in highland adult men].
AB  - Formations of red cell C3b receptor rosette, red cell immune complex and helping
      tumour red cell rosette were assayed in 194 smokers and 66 non-smokers. Results
      showed red cell C3b receptor rosette and helping tumour red cell rosette
      formation in smokers was lower than in non-smokers (P < 0.01 and P > 0.05,
      respectively), but red cell immune complex formation in smokers was higher than
      in non-smokers. Red cell C3b rosette formation decreased with the quantity and
      duration of smoking. It suggested heavily smoking for a long period could
      influence the capabilities of red cell to clear out immune complex and to adhere
      and attack the tumour cells.

PMID- 8143525
TI  - [Further studies on the factors influencing the onset of acute myocardial
      infarction].
AB  - Distribution of hospitalized cases of acute myocardial infarction (AMI) in ten
      major hospitals in Shanghai during the period of 1970-1989 was studied. A
      definite seasonal trend in admission rates of AMI was found, with the lowest in
      July and August and the peak in January, which suggested a negative relationship
      between number of admissions and average air temperature of the month. Onset of
      AMI occurred most at 6-12 o'clock in the morning, with the peaks at 8 in the
      morning, 2 afternoon, and 8 evening. Precipitating factors, such as physical
      exertion, emotional upset, could be identified in 42.03% of the patients, and
      existed more frequently in those occurred during the day than during the night.
      Based on the above findings, ways to prevent the onset of AMI were discussed in
      the paper.

PMID- 8143526
TI  - [Relationship between air pollution and mortality in Dongcheng and Xicheng
      Districts, Beijing].
AB  - Relationship between air pollution and mortality in 1989 was studied in two
      residential areas in Beijing (Dongcheng District and Xicheng District). The daily
      number of death was regressed on the logarithmic air levels of sulphur dioxide
      (SO2) and/or total suspended particulate (TSP) on the same day with Poisson
      regression method. A highly significant association was found between logarithmic
      levels of air SO2 and daily number of death adjusted for the influence of
      temperature and humidity. The stronger effects of them were seen on the death
      caused by chronic bronchitis, chronic obstructive pulmonary disease and cor
      pulmonale.

PMID- 8143527
TI  - [Detection of DNA adducts and their persistence in leucocytes of benzene-exposed
      mice].
AB  - DNA adducts in peripheral leucocytes of mice injected intraperitoneally with
      benzene were assayed by 32P-postlabelling technique. Results showed two kinds, at
      least, of DNA adducts could be formed in the mice, and they could still be
      detected 3 weeks after exposure. It laid a preliminary basis for further studies
      on the DNA adducts as biological markers for monitoring occupational exposure to
      benzene.

PMID- 8143528
TI  - [Effects of mercury exposure on reproduction in female workers].
AB  - Reproductive hazards in 704 female workers exposed to low-level metallic mercury
      and 583 controls were investigated. Females exposed to low-level mercury for a
      long term mainly manifested dysmenorrhoea, and the incidence of dysmenorrhoea
      increased with exposure dose, suggesting a dose-response relationship. At a level
      over 0.06 mg/m3 of mercury, incidence of hypomenorrhea significantly increased,
      and in general, at a level below 0.06 mg/m3, menstrual cycles, quantity and
      duration of menstrual flow did not change significantly. Differences in
      incidences of preterm delivery, spontaneous abortion, fetal death, still birth,
      and complications of pregnancy between the group exposed to 0.06-0.1 mg/m3 of
      mercury and the control group did not reach a significant level. Incidences of
      birth defect, neonatal asphyxia, neonatal death, infant infection, low birth
      weight, retardation on physical and mental development in offsprings of the
      exposed females were not significantly higher than in those of controls.

PMID- 8143529
TI  - [Experimental study on extract of Dunaliella salina in preventing NSAR-induced
      cancer of proventriculus in mice].
AB  - The preventive effect of the extracts of Dunaliella Salina (EDS) on NSAR-induced
      squamous cell cancer of proventriculus in mice was investigated. Results showed
      beta-carotene (BC) and DEC could significantly inhibit NSAR-induced
      carcinogenesis. The greatest inhibition effect was achieved in high-does- EDS
      group, with an inhibitory rate of 55.6%, but not significantly different from
      that in BC group (P > 0.05). The proliferation of spleen cells and production of
      tumour necrosis factor (TNF) by the peritoneal macrophages markedly enhanced in
      both BC and EDS groups of mice. These findings suggested the prevention of NSAR
      induced cancer of proventriculus in mice may be resulted from enhancement of cell
      immunity.

PMID- 8143530
TI  - [Advances in research on childhood injuries].

PMID- 8143531
TI  - Diagnosis of palpable breast cancer by FNA: a changing role?

PMID- 8143532
TI  - Occult breast lesions and aspiration biopsy: a new challenge.

PMID- 8143533
TI  - Cytometric validation of immunocytochemical observations in developing lung
      cancer.
AB  - Video-enhanced optical microscopy objectively confirms that immunocytochemical
      biomarker supplementation of routine cytology permits separation of (1) "pre"
      cancer epithelial cells from JHLP screened individuals who subsequently developed
      lung cancer from (2) similarly atypical epithelial cells from JHLP participants
      who did not. The establishment of a bank of sputum cytology specimens along with
      a data respository of 5-yr follow-up and clinical outcome had permitted banked
      specimens to be immunostained and scored against a gold standard of subsequent
      histologic lung cancer. A highly skilled cytopathologist, interpreting
      immunostained screening sputum specimens and blinded to the clinical outcome,
      originally was able to correctly predict clinical outcome with 88.7% accuracy
      compared to this "gold standard" (Tockman et al., J Clin Oncol 1988;6:1685-1693).
      This study presents an independent confirmation of that earlier
      immunocytochemical classification through feature extraction of digitally
      recorded, transmission optical microscope video images of immunostained,
      moderately atypical sputum cells from the original slides.

PMID- 8143534
TI  - Intraoperative cytology in breast cancer diagnosis: comparison between cytologic
      and frozen section techniques.
AB  - The diagnostic accuracy of frozen section (FS) examination and intraoperative
      cytology (IOC) has been compared in two different series of breast biopsies in
      which only one of the two methods has been used. The intraoperative results have
      been compared with the final histological diagnoses. Five-hundred-ten cases have
      been investigated by using FS only, and 407 by means of IOC. The two series were
      comparable because they included the same pathologies; moreover we have
      subdivided each series into four groups of pathologies to better evaluate the
      diagnostic accuracy of two methods. The total diagnostic accuracy of FS has been
      93.13% vs. 95.33% of IOC. The value of diagnostic accuracy of FS and IOC in the
      four sub-groups substantially overlapped; there was only a little difference in
      the group of "various lesions" in which the diagnostic accuracy of IOC was
      higher. No false positive has been observed in IOC. FS have produced one false
      positive (0.19%), whereas false negatives have amounted to 1.77% for IOC and to
      1.72% for FS. Deferred diagnoses have been 2.95% in IOC and 4.90% in FS
      examination. For both methods according to Galen and Gambino the following values
      have been calculated: sensitivity, specificity, efficiency, and predictive value.
      By comparing the data, the value of the cytological examination in the
      intraoperative diagnoses results is evident mainly when the latter is coupled
      with the gross observation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143535
TI  - Cytology of malignant melanoma of soft parts: fine-needle aspirates and
      exfoliative specimens.
AB  - We describe the morphologic features of 25 cytology specimens (13 fine-needle
      aspirates and 12 exfoliative specimens) obtained from nine patients with
      malignant melanoma of soft parts (MMSP). Analysis of the fine-needle aspirates
      and exfoliative specimens revealed primarily a dispersed cell population with
      occasional cell clustering. Tumor cells were round to polygonal with moderately
      abundant cytoplasm and had round nuclei with prominent nucleoli. In two cases, an
      initial definitive diagnosis of MMSP was rendered on material obtained by fine
      needle aspiration with the aid of immunocytochemical and ultrastructural studies.

PMID- 8143536
TI  - Fine-needle aspiration cytology diagnosis of non-Hodgkin lymphoma of thyroid: a
      report of four cases.
AB  - Four cases of non-Hodgkin lymphoma of thyroid, diagnosed by fine-needle
      aspiration (FNA) cytology during a period of 3 1/2 yr constituted 0.2% of 1,716
      thyroid FNAs and 3.4% of 118 thyroid neoplasms. The age of the patients ranged
      from 42 to 78 yr with an average of 63 yr and all were females. Three cases had
      thyroid swellings, and one case had cervical lymphadenopathy and fullness in the
      thyroid region. The lymphomas were categorized as mixed small and large cell
      lymphomas, large cell lymphoma, small noncleaved lymphoma (non-Burkitt-type), and
      plasmacytoid lymphoma. Histopathology as well as immunohistochemistry confirmed
      the cytodiagnosis of lymphoma in the first and fourth cases. In the second case
      where possibility of anaplastic carcinoma could not be ruled out altogether at
      initial cytologic examination, the histopathology report was undifferentiated
      carcinoma but immunohistochemically it was proved to be a B-cell neoplasm.

PMID- 8143537
TI  - Value of repeat cervical smears at the time of colposcopic biopsy.
AB  - At our institution, gynecologists perform Pap smears not only as an initial
      screening procedure but also at the time of colposcopy and biopsy. We compared
      the results of initial Papanicolaou (Pap) smears with those taken at colposcopic
      biopsy to determine if repeating the Pap smear at the time of colposcopy
      contributed to patient management. We found that repeat colposcopic smears often
      agreed with the referral smears and biopsies. When there was disagreement, the
      colposcopic smear was more often a lower grade than the referral smear and
      correlated best with the biopsy. Both referral and colposcopic smears
      underestimated the severity of cervical lesions with the same frequency. We could
      document only 5/414 (1.2%) colposcopic smears that contributed to patient care.

PMID- 8143538
TI  - Diagnosis of pulmonary toxoplasmosis by bronchoalveolar lavage in cardiac
      transplant recipients.
AB  - We report two cases of fatal, clinically unsuspected disseminated toxoplasmosis
      that developed following orthotopic cardiac transplantation. Toxoplasma gondii
      trophozoites, pseudocysts, and cysts were best visualized on hematoxylin and
      eosin and Giemsa-stained cytospin preparations of bronchoalveolar lavage fluid.
      Post-mortem examination in both cases revealed disseminated toxoplasmosis with
      extensive involvement of the lungs and heart. The patients, who were seronegative
      for antibody to T. gondii prior to transplantation, received organs from donors
      whose serology status was unknown. Demonstration of anti-toxoplasma antibodies
      post-transplantation occurred in both cases. Bronchoalveolar lavage may be useful
      in diagnosis of pulmonary toxoplasmosis. Clinicians, pathologists, and
      cytopathologists must consider T. gondii in the differential diagnosis of
      pneumonia in the immunocompromised patient, especially cardiac transplant
      patients.

PMID- 8143539
TI  - Benign and malignant neoplasms of myoepithelial cells: cytologic findings.
AB  - We report two myoepithelial cell neoplasms; a salivary gland tumor was malignant
      and a breast neoplasm was benign. Both were studied histologically,
      immunohistochemically, cytologically, and ultrastructurally. The malignant
      myoepithelioma recurred twice and metastasized to one regional lymph node. This
      tumor was infiltrative with areas of necrosis and hemorrhage. It was composed of
      malignant-appearing spindle and plasmacytoid cells. Both types of cells were
      immunoreactive to muscle specific actin, S-100 protein, cytokeratin, vimentin,
      and neuron-specific enolase. Ultrastructurally, features of myoepithelial cells
      were seen. Fine-needle aspirate smears showed spindle and plasmacytoid cells,
      numerous mitoses, and malignant-appearing nuclei. Spindle-cell
      adenomyoepithelioma of the breast, a small well-circumscribed firm nodule,
      featured multiple lobules of spindle cells associated with clear-cell glands at
      the lobular periphery. Histologically and cytologically, the lesion was cellular
      but appeared benign. The differential diagnosis of myoepithelial neoplasms is
      discussed.

PMID- 8143540
TI  - Cytology of cardiac myxomas: presence of Ulex europaeus agglutinin-I (UEA-I)
      lectin by immunoperoxidase staining.
AB  - Cytological findings are presented of seven cases of cardiac myxomas. Avidin
      biotin-peroxidase complex (ABC) method was employed to demonstrate Ulex europaeus
      agglutinin-I (UEA-I) lectin in imprint smears as well as in paraffin-embedded
      tissue sections in cardiac myxomas. The cytology was characterized by tumor cells
      with polyhedral or stellate and mucinous background with lymphocytes,
      neutrophils, and hemosiderin-laden macrophages. In smears as well as tissue
      sections, UEA-I lectin was detected throughout the cytoplasm of myxoma cells.
      This study established the applicability of the immunoperoxidase staining for
      cardiac myxoma as an aid in cytopathological diagnosis.

PMID- 8143541
TI  - Imprint cytology of low-grade B-cell lymphoma of mucosa-associated lymphoid
      tissue arising in the thymus: a case report.
AB  - Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in
      the thymus is a very rare tumor with characteristic morphologic features. We
      describe a case of thymic low-grade B-cell MALT lymphoma occurring in a 59-yr-old
      woman with Sjogren's syndrome, in whom the definite diagnosis was difficult at
      the time of surgery. An immunohistologic and genotypic study, however, was
      diagnostic of lymphoma. A review of cytologic material was undertaken, and it was
      felt that the cytologic features in Giemsa-stained preparations in imprint smears
      were present that initially should have enabled the correct cytodiagnosis and
      distinction from the other thymic lesions. The findings presented in this study
      were considered to contribute to the cytodiagnosis of a thymic lesion, which
      might, in the past, have been erroneously interpreted as another
      lymphoproliferative disorder.

PMID- 8143542
TI  - Fine-needle aspiration cytology of a membranous basal cell adenoma arising in an
      intraparotid lymph node.
AB  - The so-called membranous basal cell adenoma is a rare subtype of monomorphic
      adenomas that usually presents in the parotid gland. The cytologic, histologic,
      and immunohistochemical findings of an example of this entity, arising in an
      intraparotid lymph node of a 75-yr-old woman, are reported. Only 7 cases of this
      tumor have been published in such a peculiar location. As far as we know, fine
      needle aspiration cytology has never been performed.

PMID- 8143543
TI  - Leishmania lymphadenitis diagnosed by fine-needle aspiration biopsy.
AB  - A case of Leishmania lymphadenitis which presented clinically as an isolated left
      laterocervical lymph node is described. Diagnosis was made by fine-needle
      aspiration biopsy (FNAB), as in other cases previously reported. The material
      obtained yielded abundant histiocytes, multinucleated giant cells, and
      epithelioid microgranulomas with Leishman-Donovan pathognomic bodies in the
      cytoplasm of cells, together with free forms of the parasite. This paper comments
      on the main differential diagnoses to be considered in our region when faced with
      granulomatous adenitis and the role of FNAB in the identification of this
      parasite in endemic areas.

PMID- 8143544
TI  - Fine-needle aspiration of epithelioid sarcoma.
AB  - The cytologic appearance of epithelioid sarcoma in fine-needle aspiration biopsy
      (FNAB) has not been extensively described. The authors report the cytologic
      findings in one case that metastasized to a lymph node. The cells are
      characterized by irregular nuclei, nuclear folds, macronucleoli, and a high
      nucleus-cytoplasm ratio. The cells vary in shape and occur singly and in clusters
      where intercellular spaces are uncommon. The findings allow the diagnosis of
      malignancy but are nonspecific. History, immunocytochemistry, and tissue cores
      are helpful in the differential diagnosis.

PMID- 8143545
TI  - Cytodiagnosis of pseudomyxoma peritonei in cases suspected of ovarian tumours.
AB  - The cytologic features in four cases of pseudomyxoma peritonei are described in
      ascitic fluid specimens which were received from female patients suspected of
      ovarian masses. The findings in the fluid included cells of mesothelial origin
      and spindle-shaped fibroblasts with a significant amount of background mucin.
      This was confirmed by mucicarmine and Alcian blue stains. A cytologic diagnosis
      of pseudomyxoma peritonei was possible in all four cases. The above findings were
      further substantiated since mucinous ovarian neoplasms were found in all the
      cases.

PMID- 8143546
TI  - Quantitative analysis of mast cells in testicular aspiration cytology smears in
      azoospermic males.
AB  - Quantitative estimation of mast cells was done in testicular aspiration cytology
      smears of 90 azoospermic males. Cases included normal spermatogenesis (32),
      Sertoli cell only (38), late maturation arrest (16), and early maturation arrest
      (4). The pooled number of mast cells in 20 standard fields in Sertoli cell only
      and late maturation arrest cases were significantly higher than that of normal
      spermatogenesis (P < .001 and P < .01 respectively). Aggregates of mast cells
      were found around the seminiferous tubules in Sertoli cell only cases. The
      findings suggest that increased number of mast cells may be the cause or effect
      of testicular damage in idiopathic male infertility.

PMID- 8143547
TI  - Fine-needle aspiration cytology of diabetic fibrous mastopathy.
AB  - Diabetic fibrous mastopathy, also known as lymphocytic mastitis, is an uncommon
      lesion of the breast that occurs in women with long-standing insulin-dependent
      diabetes mellitus (IDDM). To my knowledge, the fine-needle aspiration findings of
      a histologically confirmed case of diabetic fibrous mastopathy have not been
      previously described and illustrated in the cytology literature.

PMID- 8143548
TI  - Fine-needle aspiration cytology of the male breast in a cancer center.
AB  - All fine-needle aspirates (FNA) performed on the male breast at The University of
      Texas M. D. Anderson Cancer Center from 1985 to 1992 were reviewed, totaling 64.
      The patients' ages ranged from 19 to 86 years, with a mean of 56 years. Thirty
      three patients had a history of an extramammary malignancy. The diagnoses
      established by FNA were gynecomastia (45), mammary carcinomas (6), neoplasms
      metastatic to the breast (5), suspicious for carcinoma (1), intra-mammary lymph
      node (1), and lipoma (1). In five cases the aspirates were nondiagnostic. Two of
      these proved to be gynecomastia on subsequent histologic examination. Of the six
      FNA cases initially thought to represent primary breast carcinomas, two were
      found to be secondary because of involvement of the underlying chest wall by
      mesothelioma (1), and mucinous adenocarcinoma, unknown primary (1). No false
      positive diagnosis was rendered. We conclude that fine-needle aspiration of the
      male breast is a reliable means of assessment; however, unique problems may be
      encountered compared with aspiration of the female breast. These include the
      epithelial hyperplasia frequently associated with gynecomastia, the relatively
      equal frequency of primary and metastatic breast lesions when a malignant process
      is discovered, and chest wall lesions masquerading as breast lesions.

PMID- 8143549
TI  - Malacoplakia and Rosai-Dorfman disease: two entities of histiocytic origin
      infrequently localized in the female breast--the cytologic aspect in aspirates
      obtained via fine-needle aspiration cytology.
AB  - We describe one case of Rosai-Dorfman disease (RDD) localized in the breast and
      one case of breast malacoplakia (MPK) both diagnosed by fine-needle aspiration
      cytology (FNAC). In RDD the cytologic features were lymphocytophagocytosis, large
      histiocytes with slight nuclear atypia, and lymphohistiocytic aggregates in a
      polymorphous background which included frequent plasma cells. In MPK the key
      diagnostic feature was the presence of Michaelis-Gutmann bodies (M-G bodies), in
      various stages of evolution, intermingled with vacuolized medium-sized
      histiocytes, other inflammatory cells, and debris. Pap staining is the technique
      of choice to show lymphocytophagocytosis and M-G bodies and there is no need to
      resort to special staining methods. RDD and MPK share a common cytologic
      background: the presence of numerous benign reactive histiocytes, either
      engulfing apparently intact lymphocytes, or phagocytizing M-G bodies. The
      cytologic findings seen in both cases suggest that the presence of histiocytes in
      a breast aspirate is far from being nonspecific and can represent an important
      lead to disparate diseases such as RDD and MPK.

PMID- 8143550
TI  - Aspiration cytology of clear-cell lesions of the parotid gland: morphologic
      features and differential diagnosis.
AB  - Clear-cell lesions of the parotid gland are uncommon but when studied by fine
      needle aspiration may result in a clinically important but cytologically
      difficult differential diagnosis. Clear-cell lesions involving the parotid
      include acinic cell neoplasm, clear cell oncocytoma, mucoepidermoid carcinoma,
      primary clear-cell carcinoma, epithelial-myoepithelial carcinoma, and metastatic
      renal cell carcinoma. Accurate diagnosis is achieved by assessment of nuclear
      features, other cell populations present, and clinical data including
      radiographic studies.

PMID- 8143551
TI  - Can FNA biopsy separate atypical hyperplasia, carcinoma in situ, and invasive
      carcinoma of the breast?: Cytomorphologic criteria and limitations in diagnosis.

PMID- 8143552
TI  - Tissue salvage from aspirate smears.

PMID- 8143553
TI  - Obstructive sleep apnea.
AB  - The high prevalence of obstructive sleep apnea (OSA) has only recently been
      appreciated, in part because the symptoms and signs of chronic sleep disruption
      are often overlooked in spite of their debilitating consequences. They typically
      develop insidiously during a period of years. We now know that the lives of
      millions of people each year are significantly impaired by the sequelae of OSA.
      Many of these patients go unrecognized, with tremendous medical and economic
      consequences for individual patients and for society. Evidence indicates that
      chronic, heavy snoring may be associated with increased long-term cardiovascular
      and neurophysiologic morbidity. Therefore considerable interest lies in the study
      of the epidemiology and the natural history of these related disorders. The
      fundamental problem in OSA is the periodic collapse of the pharyngeal airway
      during sleep. The pathophysiology of this phenomenon is reviewed in some detail.
      During apneas caused by obstruction, airflow is impeded by the collapsed pharynx
      in spite of continued effort to breathe. This causes progressive asphyxia, which
      increasingly stimulates breathing efforts against the collapsed airway, typically
      until the person is awakened. Hypopneas predominate in some patients and are
      caused by partial pharyngeal collapse. The clinical sequelae of OSA relate to the
      cumulative effects of exposure to periodic asphyxia and to sleep fragmentation
      caused by apneas and hypopneas. Some patients with frequent, brief apneas and
      hypopneas and normal underlying cardiopulmonary function may have considerable
      sleep disruption without much exposure to nocturnal hypoxia. Patients with sleep
      apnea often have excessive daytime sleepiness. As the disorder progresses,
      sleepiness becomes increasingly irresistible and dangerous, and patients develop
      cognitive dysfunction, inability to concentrate, memory and judgment impairment,
      irritability, and depression. These problems may lead to family and social
      problems and job loss. Cardiac and vascular morbidity in OSA may include systemic
      hypertension, cardiac arrhythmias, pulmonary hypertension, cor pulmonale, left
      ventricular dysfunction, stroke, and sudden death. The challenge for the
      clinician is to routinely consider the diagnosis and to incorporate several basic
      questions in the historical review of systems regarding daytime or inappropriate
      sleepiness. The diagnosis of OSA is made with polysomnography, and the decision
      to treat is based on an overall assessment of the severity of sleep-disordered
      breathing, sleep fragmentation, and associated clinical sequelae. The therapeutic
      options for the management of OSA are reviewed. Recognition and appropriate
      treatment of OSA and related disorders will often significantly enhance the
      patient's quality of life, overall health, productivity, and safety on the
      highways.

PMID- 8143554
TI  - [The results of percutaneous diskectomy. The course of pain, work capacity and
      therapy failure].
AB  - In a prospective study extending from November 1989 to December 1992 percutaneous
      discectomy was carried out in 50 patients (26 men, 24 women, mean age 41 [19-73]
      years). The aim of the study was to ascertain the efficacy of this new mode of
      treatment, and its indications. The patients selected for the procedure had
      chronic, therapy-resistant lumboradicular pain syndrome of at least six weeks'
      duration; imaging procedure had to show a "bulging disc" and neurological
      deficits had to be no more than minor. During the subsequent follow up period of
      22 +/- 9.6 months 35 of the 50 patients did not require any further surgery; 24
      of them (69%) resumed full work while seven (20%) regained partial (50%) working
      capacity. However, the operation proved ineffective in four of these 35 patients
      (11%). Fourteen of the 50 patients (28%) had persistent pain and required
      revision by open classical discectomy; seven of them resumed full work and one
      regained 50% working capacity. The most frequent findings at this revision were
      stenosis of the subarticular recess in combination with persistent forward
      bulging of the longitudinal ligament and anulus fibrosus (n = 7), calcification
      of the posterior longitudinal ligament (n = 1) and an intervertebral disc
      sequestrum which gave a false negative results on discography (n = 2). In another
      case there was a genuine recurrence 35 months after a successful percutaneous
      procedure; this was treated successfully by open operation. When performed at the
      level L5/S1, the procedure gave unsatisfactory results in five out of six
      cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143555
TI  - [The treatment of type-1 diabetics with insulin-induced lipohypertrophy by
      liposuction].
AB  - Extensive areas of lipohypertrophy at the insulin injection sites on both thighs,
      upper arms and buttocks had developed in a 22-year-old woman with type 1
      diabetes. Tissue biopsy showed fat cells of normal size, while the stromal cells
      in primary culture from the lipohypertrophy tissue demonstrated a greater degree
      of new fat-cell formation than normal fat tissue, i.e. there was fat-cell
      hyperplasia. Although the patient avoided these sites for insulin injection
      during the subsequent 18 months, the amount of excessive fat tissue did not
      decrease. As the very obvious fat pads distressed the patient, local liposuction
      was applied without complication at the six affected sites, removing a total of
      2,000 ml of fat.-Liposuction is a low-risk curative procedure for removing
      extensive insulin-induced lipohypertrophic tissue and quickly achieves a
      cosmetically satisfactory result.

PMID- 8143556
TI  - [Rickettsiosis of the typhus fever type. Its joint appearance with a left
      ventricular thrombus and single-vessel coronary disease].
AB  - A 44-year-old German fell ill in Libya, where he had been living for 10 years,
      with high fever, rigor and a nonitching centrifugally spreading macular rash,
      which had spared the head, hands and soles. In addition, a systolic cardiac
      murmur was heard. The Weil-Felix reaction had a titre rising within 3 days from
      1:160 to 1:640, confirming the diagnosis of rickettsial disease, the total
      clinical picture indicating typhus. On treatment with chloramphenicol (1 g three
      times daily i.v.) the fever subsided within 5 days. On the ninth day treatment
      was changed to oral doxycyclin, 200 mg daily for 3 weeks. Echocardiography
      surprisingly revealed a floating thrombus, about 4 x 8 cm, attached to the hypo-
      and even akinetic apex of the left ventricle. In addition there was single-vessel
      coronary disease. Since the segmental contraction abnormality persisted after the
      typhus had been cured, a causal connection with the rickettsial disease is
      unlikely. The thrombus was removed at the time of a aortocoronary bypass
      operation: his course has been unremarkable since then.

PMID- 8143557
TI  - [The rational diagnosis of HIV infection].

PMID- 8143558
TI  - [The fibromyalgia syndrome. A neuroendocrinological autoimmune disease?].

PMID- 8143559
TI  - [The premature hospital release of suicide-prone patients].

PMID- 8143560
TI  - [A heparin bolus in acute myocardial infarct?].

PMID- 8143561
TI  - [Ketamine in emergency medicine].

PMID- 8143562
TI  - [The control of feeding tubes].

PMID- 8143563
TI  - [Polyostotic fibrous dysplasia of the spinal column and ribs].

PMID- 8143564
TI  - [The coagulation parameters in high-dosage intravenous heparin therapy].

PMID- 8143566
TI  - [Chronic liver diseases and hepatocellular carcinoma].

PMID- 8143565
TI  - [The diagnosis and therapy of pancreatic carcinoma].

PMID- 8143567
TI  - Pulsed ultrasound and electrocortical activity in fetal sheep.
AB  - The aim of this study was to determine if low intensity ultrasound affects
      electrocortical activity in chronically instrumented fetal sheep. A 3.5-MHz
      transducer was attached to each fetal skull (n = 9) and activated periodically to
      emit pulses of 5.8 microseconds duration at a repetition rate of 2 kHz generating
      a power output of 60 mW. The power supply was activated in 30-s bursts every 180
      s but random electronic switching energized the transducer with 50% of bursts. On
      average, 175 bursts of ultrasound were delivered to the fetus over 19.5 h.
      Blinded analysis of continuous recordings of electrocortical activity showed it
      to be unaffected by the ultrasound exposures. Therefore, it is unlikely that
      ultrasonic examination of human fetuses will affect normal cyclical
      electrocortical activity.

PMID- 8143568
TI  - Effects of nonrigid reclining infant seat on preterm behavioral states and motor
      activity.
AB  - Twenty preterm neonates in an intensive care unit (mean gestational age, 30
      weeks; mean birthweight, 1375 g) were randomly assigned to an experimental or a
      control group. The experimental infants were placed twice a day (for 3-h
      sessions) in a nonrigid reclining seat for a 6- to 7-week period. Before
      discharge from intensive care, the behavioral states and motor activity of the
      neonates were monitored during sleep-wake behavior observations (2 h). The
      experimental group subjects slept more, were quieter, and made fewer movements
      such as cloni, contraction and startles. The discussion centers on the distinct
      advantages of using nonrigid infant seats in a reclining position in intensive
      care units.

PMID- 8143569
TI  - There are no rest-activity dependent changes in fetal ductus arteriosus flow
      velocity patterns at 27-29 weeks of gestation.
AB  - Blood flow velocity waveforms recorded in the fetal ductus arteriosus were
      related to fetal heart rate pattern (FHRP) in 13 normal pregnancies at 27-29
      weeks of gestation. Recording time was always 65 min or more. In three women no
      low fetal heart rate (FHRP-A) variability was present, in the remaining 10 women
      high fetal heart rate (FHRP-B) variability was established in 80% of the
      recording time. There was no statistically significant difference between FHRP-A
      and FHRP-B pattern for all ductal flow velocity parameters, indicating rest
      activity state independency in late second and early third trimester pregnancy.

PMID- 8143570
TI  - Pancreatic exocrine function and necrotising enterocolitis.
AB  - Pancreatic protease deficiency may be an aetiological factor in enteritis
      necroticans, a disease sharing some features of necrotising enterocolitis (NEC).
      Using faecal chymotrypsin measurement we have prospectively studied pancreatic
      exocrine function in infants at risk of NEC. No significant difference was found
      comparing those infants who subsequently developed NEC and those who did not.

PMID- 8143571
TI  - Congenital adrenal hyperplasia (CAH)--the place for prenatal treatment and
      neonatal screening.
AB  - What are the respective places for prenatal treatment and neonatal screening in
      21 hydroxylase deficiency, (21OHD) CAH? Current diagnostic procedures for 21OHD
      CAH do not prevent potential or actual morbidity and mortality from salt wasting
      and hypoglycaemia, ambiguous genitalia and late diagnosis. Presentation is with
      life-threatening illness or virilisation with long-term physical, psychological
      and psychosexual sequelae. Screening the whole newborn population would add only
      a very small additional unit cost in the screening laboratory already measuring
      TSH and phenylalanine. There are still few data on which to base an assessment of
      the efficacy of neonatal screening in reducing morbidity and mortality. Screening
      should now be adopted on a regional, or national, basis to assess both efficacy
      and cost-effectiveness. Although more (uncontrolled) data are now available
      concerning prenatal dexamethasone therapy, the degree of benefit in terms of
      reduced virilisation in relation to potentially significant maternal side effects
      is unclear and possible long term childhood side effects have not been studied.
      At present, therefore, there is insufficient evidence regarding the safety of
      mother and fetus to recommend the general use of dexamethasone outwith the
      context of controlled scientific studies. There is an urgent need for prospective
      controlled studies to be undertaken which would, in time, resolve both questions.

PMID- 8143572
TI  - Predictive value of general movements in asphyxiated fullterm infants.
AB  - The developmental course of spontaneous motility was investigated in a group of
      26 fullterm infants, affected by mild to severe hypoxic-ischaemic encephalopathy.
      Serial 1-h videorecordings were carried out from birth to 15-22 weeks and a
      quality assessment of general movements (GMs) was made from a replay of the
      videos. Neurological follow-up of the infants were continued until at least 18
      months of age; neonatal EEG and neuro-imaging techniques (US-scan, CT or MRI)
      were also carried out in all cases. The results indicate that perinatal asphyxia
      has important effects on the spontaneous motility of fullterm infants.
      Hypokinesis occurred very frequently during the first days of life, followed by a
      transient or prolonged (lasting longer than 15-22 weeks) abnormal quality of GMs.
      In the first 2 weeks the results of GM assessment did not correlate with the
      simultaneous findings of neurological examination, neuro-imaging and EEG, whereas
      they did when the results at 15-22 weeks were considered. The changes in
      spontaneous motility and especially GM developmental trajectories were good
      predictors of the neurological outcome. The predictive value of GM assessment was
      found to be similar to that of EEG and neuro-imaging, and better than
      neurological examination.

PMID- 8143573
TI  - Methods for removing metal obstructions from the root canal.
AB  - The removal of metallic obstructions is an important part of endodontic
      retreatment procedures and encounters a number of serious problems. Sometimes
      removal procedures are extremely easy and can be performed in rather short time,
      but often it is a very tedious and time-consuming operation with a high number of
      failures, especially with fractured instruments. Using special devices such as
      the Masserannkit, the Canal-Finder-System, or ultrasonic systems some fractured
      instrument cases can be managed successfully. The retreatment of dowel-obturated
      root canals or failing silver cone cases has a good prognosis and a fairly good
      success rate. The Masserannkit, post pullers, the Canal-Finder-System and
      ultrasonic systems have been shown to be helpful devices in removal of root posts
      and silver cones. Additionally a large number of special devices and techniques
      for the removal of metal obstructions from the root canal have been described in
      the literature and will be critically reviewed.

PMID- 8143574
TI  - Partial pulpotomy in young permanent teeth with deep carious lesions.
AB  - The material comprised 37 young posterior teeth with deep carious lesions and
      exposed pulps, treated with partial pulpotomy and dressed with calcium hydroxide.
      The teeth were divided into two groups. Group 1 consisted of 31 teeth with no
      clinical or radiographic symptoms before treatment, Group 2 of 6 teeth with
      temporary pain, widened periodontal space periapically and/or productive
      osteitis, i.e. increased density of the surrounding alveolar bone. After an
      observation time of 24 to 140 months (mean = 56 months), healing had occurred in
      29 of 31 teeth in Group 1 (93.5%) and in 4 of 6 teeth in Group 2. It was
      concluded that the present, as well as previously reported results indicate that
      partial pulpotomy may be an adequate treatment for young permanent molars with a
      carious exposure, although more studies are needed before the treatment can be
      recommended for routine clinical use.

PMID- 8143575
TI  - Efficacy of chlorhexidine in disinfecting dentinal tubules in vitro.
AB  - Solutions of 0.2% and 2% chlorhexidine, 0.2% and 2% sodium hypochlorite (NaOCl)
      and normal saline were tested for their efficacy in disinfecting dentinal tubules
      following root canal irrigation in vitro. Freshly extracted bovine incisor roots
      were prepared as cylindrical shapes, 4 mm high and 5 mm wide with a lumen 2.1 mm
      wide. After mechanical removal of the cementum and elimination of the smear layer
      on the dentine surface with EDTA and NaOCl, the root sections were autoclaved and
      the dentinal tubules infected with E. faecalis (NCTC 775) by incubating in yeast
      extract glucose broth for 1 week. The root canals were irrigated with 20 ml of an
      irrigant solution using a syringe. Each irrigant was used in six specimens.
      Dentine was removed from the canal wall by sterile burs of increasing diameter to
      give samples 100, 100-300 and 300-500 microns deep. The dentine samples were then
      cultured to determine the presence and quantity of remaining micro-organisms. The
      results indicated that chlorhexidine and NaOCl were equally effective
      antibacterial agents at similar concentrations against the test microorganism.
      They significantly reduced the bacterial counts in the first 100 microns of
      dentinal tubules, however up to 50% of dentine samples remained infected
      following use of both agents.

PMID- 8143576
TI  - In vitro evaluation of the effectiveness of calcium hydroxide and
      paramonochlorophenol on anaerobic bacteria from the root canal.
AB  - The effectiveness of calcium hydroxide and paramonochlorophenol (PMCP) was tested
      on anaerobic bacteria isolated from infected root canals, at time intervals 5,
      15, 30 and 60 min. The experimental method used was similar to that proposed by
      the German Society of Hygiene and Microbiology (DGHM), with slight modifications.
      Testing revealed that calcium hydroxide was significantly more effective than
      PMCP against the total number of anaerobes. Additionally, it was proved to be
      quickly and highly effective against some microorganisms related to severe
      clinical symptoms, such as B. melaninogenicus and P. gingivalis, as well as
      against actinomyces species.

PMID- 8143577
TI  - Root canal therapy of an anomalous maxillary central incisor: a case report.
AB  - A case of endodontic conservative treatment of a maxillary central incisor with
      an atypical crown and Type III dens invaginatus is presented. The greatest
      difficulty was to locate the root canals due to the atypical internal anatomy.
      There were not two clear canals, but the coronal pulp chamber showed two
      entrances to the root canal. The tooth presented a distal periodontal pocket and
      various lingual radicular grooves. The appearance of the crown was improved by
      alteration of its dimension using diamond rotary instruments and correction with
      photopolymerized resin.

PMID- 8143578
TI  - Prevention of environmental pollution: good for our health.

PMID- 8143579
TI  - Asbestos findings questioned.

PMID- 8143580
TI  - Methyl ethyl ketone and methyl isobutyl ketone not carcinogenic.

PMID- 8143581
TI  - Breast cancer and menarche in Asian women.

PMID- 8143582
TI  - CDC's new chief.

PMID- 8143583
TI  - Look Ma--no cancer.

PMID- 8143584
TI  - Pollution plagues NAFTA south of the border.

PMID- 8143585
TI  - Feds to clean up their acts.

PMID- 8143586
TI  - Biodiversity blind.

PMID- 8143587
TI  - Dioxin and endometriosis.

PMID- 8143588
TI  - University of Rochester--leaders in heavy metals.

PMID- 8143589
TI  - Are pesticides a problem?

PMID- 8143590
TI  - Signs of an olive branch: confronting the environmental health consequences of
      the Midwestern floods.

PMID- 8143591
TI  - Natural disasters and man-made responses: are we protecting environmental health?

PMID- 8143592
TI  - Using the techniques of molecular biology to search for novel insecticides.

PMID- 8143594
TI  - Inuit exposure to organochlorines through the aquatic food chain in arctic
      quebec.
AB  - Inuit people (Eskimos) are likely exposed to persistent organochlorine compounds
      because their traditional diet includes fatty tissues of the arctic marine biota.
      Here we present the results of organochlorine compound analysis in milk fat
      samples from arctic Quebec Inuit women and in fat tissues from various animal
      species inhabiting that region. The total concentration of polychlorinated
      biphenyl congeners in Inuit milk fat was similar to that of the beluga, while the
      profile of the 10 congeners resembled that of the polar bear. Mean concentrations
      of various organochlorines in milk-fat samples from Inuit women were between 2
      and 10 times greater than those found in samples previously collected from
      southern Quebec women. The Inuit mothers exhibit the greatest body burden known
      to occur from exposure to organochlorine residues present in the environment by
      virtue of their location at the highest trophic level of the arctic food web.

PMID- 8143593
TI  - An age-specific kinetic model of lead metabolism in humans.
AB  - Although considerable progress has been made in recent years in reducing human
      exposures to lead, the potential for high intake of this contaminant still exists
      in millions of homes and in many occupational settings. Moreover, there is
      growing evidence that levels of lead intake considered inconsequential just a few
      years ago can result in subtle, adverse health effects, particularly in children.
      Consequently, there have been increased efforts by health protection agencies to
      develop credible, versatile methods for relating levels of lead in environmental
      media to levels in blood and tissues of exposed humans of all ages. In a parallel
      effort motivated largely by the Chernobyl nuclear accident, the International
      Commission on Radiological Protection (ICRP) is assembling a set of age-specific
      biokinetic models for calculating radiation doses from environmentally important
      radionuclides, including radioisotopes of lead. This paper describes a new age
      specific biokinetic model for lead originally developed for the ICRP but expanded
      to include additional features that are useful for consideration of lead as a
      chemical toxin. The model is developed within a generic, physiologically
      motivated framework designed to address a class of calciumlike elements. This
      framework provides a useful setting in which to synthesize experimental,
      occupational, and environmental data on lead and exploit common physiological
      properties of lead and the alkaline earth elements. The modular design is
      intended to allow researchers to modify specific parameter values or model
      components to address special problems in lead toxicology or to incorporate new
      information. Transport of lead between compartments is assumed to follow linear,
      first-order kinetics provided the concentration in red blood cells remains below
      a nonlinear threshold level, but a nonlinear relation between plasma lead and red
      blood cell lead is modeled for concentrations above that level. The model is
      shown to be consistent with data on human subjects exposed to lead under a
      variety of experimental and natural conditions.

PMID- 8143595
TI  - Influence of pentachlorophenol on light emission from single barnacle muscle
      fibers preloaded with aequorin.
AB  - Experiments show that the resting ouabain-insensitive sodium efflux in giant
      fibers from the barnacle Balanus nubilus is stimulated by external application of
      pentachlorophenol (PCP). This work has now been extended to include a study of
      muscle fibers preloaded with the Ca2+ indicator aequorin to determine whether PCP
      is able to increase light emission; and whether its potency depends on the number
      of chlorine atoms and external pH. The results obtained are as follows: 1) PCP
      causes a dose-dependent, multiphasic rise in light emission; the threshold
      concentration in fibers not poisoned with ouabain was in the low micromolar
      range. 2) The efficacy of PCP is considerably greater than that of less
      chlorinated phenols and phenol. 3) The response to PCP is a sigmoidal function of
      external pH both in unpoisoned and ouabain-poisoned fibers. Reducing external pH
      potentiates its efficacy. 4) The response to PCP depends on the external Ca2+
      concentration, and the requirement for Ca2+ is usually absolute.

PMID- 8143596
TI  - Identification and characterization of populations living near high-voltage
      transmission lines: a pilot study.
AB  - Populations living close to high-voltage transmission lines often have
      residential magnetic field exposures in excess of 1 microT, and sometimes over 2
      microT. Yet, populations studied in most epidemiologic investigations of the
      association between residential magnetic field exposure and cancer typically have
      exposures below 1 microT and frequently below 0.5 microT. To improve statistical
      power and precision, it would be useful to compare high exposure populations with
      low exposure populations rather than only studying small differences within low
      exposure populations. Toward this end, we have developed an automated method for
      identifying populations living near high-voltage transmission lines. These
      populations likely have more highly exposed individuals than the population at
      large. The method uses a geographic information system (GIS) to superimpose
      digitized transmission line locations on U.S. Census block location data and then
      extract relevant demographic data. Analysis of data from a pilot study of the
      populations residing within 100 m of a 29-km segment of one 230-kV line in New
      Jersey shows that when compared to populations in the surrounding census blocks
      farther than 100 m from this line, those populations close to the line have
      similar demographics but differ in terms of perceived housing value variables. We
      believe that the approach we have developed will enable investigators to rapidly
      identify and characterize populations living near high-voltage transmission lines
      on a statewide basis for considering the impact of exposures and for public
      policy and that these populations also can be used for epidemiologic study.

PMID- 8143598
TI  - The fourth United States-Japan meeting on the toxicological characterization of
      environmental chemicals.

PMID- 8143597
TI  - Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with
      DEN: histologic, biochemical, and cell proliferation endpoints.
AB  - The present study examines the dose-response relationship for 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical
      parameters by using a two-stage model for hepatocarcinogenesis in female Sprague
      Dawley rats initiated with a single intraperitoneal dose of 175 mg of
      diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after
      initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil
      once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg
      body weight/day. A significant body weight reduction was present in the
      noninitiated group that received 125 ng TCDD. Relative liver weight was
      statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in
      noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of
      cytotoxicity was dose-related in all TCDD-treated groups. There was a
      statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase
      labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally
      significant trend in the saline-treated rats (p = 0.10), but proliferating cell
      nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed
      no increase. Among the DEN-initiated groups there was a significant increase in
      glutathione S-transferase altered hepatic foci stereological parameters in the
      125 ng TCDD group. This study demonstrates that dose-response relationships for
      TCDD's effects on cell proliferation growth of altered hepatic foci are different
      from previously reported effects on P450 gene expression, indicating that
      different biological or biochemical responses may exhibit different dose-response
      relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143599
TI  - The cytokinesis-block micronucleus technique and its application to genotoxicity
      studies in human populations.
AB  - The development of the cytokinesis-block (CB) technique has made the human
      lymphocyte micronucleus assay (MN) a reliable and precise method for assessing
      chromosome damage. Recent studies in our laboratory have confirmed that this
      method is a sensitive indicator of in vivo radiation exposure in patients
      undergoing fractionated partial-body radiotherapy and rodents exposed to uniform
      whole-body irradiation, thus supporting the application of the cytokinesis-block
      micronucleus (CBMN) assay for biological dosimetry. To further define the use of
      this assay in biomonitoring, we have also undertaken extensive studies to
      determine the spontaneous level of MN in normal human populations and its
      relationship to various lifestyle factors. During the past year, we have also
      developed a new variation to the CBMN assay that enables the conversion of
      excision-repairable lesions to MN within one cell-cycle using cytosine
      arabinoside. With this method the slope of the in vitro dose-response curves was
      increased by a factor of 1.8 for X-rays, 10.3 for ultraviolet (254 nm) radiation,
      and approximately 40-fold for methylnitrosourea. Consequently, the CBMN assay can
      now be used not only to measure whole chromosome loss or chromosome breaks but
      also excision repair events. The versatility and simplicity of the CBMN assay
      together with new developments in automation should enable its successful
      application in monitoring exposed populations as well as identifying mutagen
      sensitive individuals within a population.

PMID- 8143600
TI  - Using the micronucleus assay to detect genotoxic effects of metal ions.
AB  - The lymphocyte micronucleus assay was used to measure the average frequency of
      micronuclei in a population and thus assess genotoxic effects. Data from 174
      persons give an average value of 16.4 +/- 7.3, and a slight age-dependence was
      observed. To detect combined environmental mutagen injuries the micronucleus
      assay was used to study the effects of metal compounds. Cadmium ions increased
      the micronucleus frequency linearly after incubation with whole blood in vitro
      with 10(6)-10(-3) M concentrations for 30 min. Similarly, a linear increase in
      micronucleus frequency was detected with 10(-3)-10(-1) M mercury ions. Concerning
      the biological effect of selenium, it was found that neither sodium selenite nor
      selenium dioxide induced increases at concentrations of 10(-7)-10(-6) M; 10(-5) M
      caused a slight increase; 10(-4) M, however, destroyed the cells. These results
      suggest that the human lymphocyte micronucleus test can be used to assess
      genotoxic injuries due to environmental effects in human lymphocytes.

PMID- 8143601
TI  - Radium-226-contaminated drinking water: hypothesis on an exposure pathway in a
      population with elevated childhood leukemia.
AB  - A recent epidemiological survey on childhood malignant disease in the region of
      Ellweiler, Rheinland-Pfalz, Germany, revealed a significantly increased incidence
      of childhood leukemia, but observed incidences of lymphoma and solid tumors were
      normal. Established risk factors such as individual exposure to chemicals as well
      as hereditary genetic disorders were ruled out in interviews with the patients or
      their families. The general population in the region, however, is subjected to
      considerable doses of ionizing radiation due to high levels of external gamma
      radiation and high activities of indoor radon. Radiation-specific chromosome
      aberrations were found in one of two healthy siblings and one father of leukemia
      patients as well as in any of three probands living in houses with high indoor
      radon activities. Radon and natural gamma radiation, however, cannot explain the
      geographical pattern of the cases. Four out of seven cases were observed in two
      particular villages near a uranium processing plant. The drinking water of these
      villages partly came from a small river that was contaminated with radium-226
      washed out from the dumps of the uranium plant. Only sparse measurements of 226Ra
      are available, but derived red bone marrow doses for children in the two villages
      obtained from a simple radio-ecological model show the significance of the
      drinking water pathway. Prenatal 226Ra exposure of fetuses due to placental
      transfer and accumulation may have led to significant doses and may explain the
      excess cases of childhood leukemia in the region even in quantitative terms.

PMID- 8143602
TI  - New opportunities in cancer risk evaluation using PCR-based DNA analysis for
      CYP2D6.
AB  - Genetic polymorphisms of drug-metabolizing enzymes, principally CYP2D6
      (debrisoquine 4-hydroxylase), have long been considered influential on host
      responsiveness to environmental carcinogens. In several independent studies, lung
      cancer cases are more frequently associated with the extensive metabolizer
      phenotype of CYP2D6. However, assignment of phenotype has traditionally involved
      administration of debrisoquine and analysis of drug and metabolite concentrations
      in patient urine and is thus potentially confounded by concomitant drug therapy
      and the presence of the tumor itself. The development of molecular genotyping
      methods offers unique opportunities to obviate these problems and to ascertain
      the relationship between the presence of individual alleles and disease risk.
      Preliminary data are presented that indicate that the CYP2D6 wild-type allele may
      be a predisposing factor in lung cancer.

PMID- 8143603
TI  - Measurement of chromosomal aberrations, sister chromatid exchange, hprt
      mutations, and DNA adducts in peripheral lymphocytes of human populations at
      increased risk for cancer.
AB  - Using a multidisciplinary approach, we have measured various indicators of DNA
      damage in peripheral lymphocytes of human populations potentially at increased
      risk for cancer. Sister chromatid exchanges (SCE) and polycyclic aromatic
      hydrocarbon (PAH)-DNA adducts were evaluated in a group of firefighters;
      chromosomal aberrations and hprt mutations were evaluated in a group of cancer
      patients undergoing radioimmunoglobulin therapy (RIT); SCE and acrolein-modified
      DNA were measured in cancer chemotherapy patients and in pharmacists preparing
      chemotherapy prescriptions; and SCE and PAH-DNA adducts are being measured in
      U.S. army troops stationed in Kuwait. Our results indicate that both SCE and PAH
      DNA adduct levels were not elevated in firefighters, but that other factors such
      as smoking status and race were risk factors for increased SCE and PAH-DNA
      adducts. RIT was found to increase background rates of chromosome-type
      aberrations and frequencies of hprt mutations and there was a strong correlation
      between levels of therapy-induced chromosome damage sustained in vivo and in
      vitro sensitivity to radiation-induced chromosome damage. Peripheral blood
      lymphocytes of cancer patients treated with cyclophosphamide showed higher levels
      of SCE and had a higher incidence of acrolein adducts in DNA. Lymphocytes from
      pharmacists preparing antineoplastic drugs were found to acquire increased in
      vitro sensitivity to SCE induction by phosphoramide mustard with increased
      lifetime duration of drug handling. A prospective, longitudinal study was
      performed to identify environmental factors that modulate genetic damage in
      breast cancer patients. Women with benign breast masses and no apparent disease
      served as controls. Mutant frequency, cloning efficiency, and chromosomal
      aberration frequency did not differ significantly among the three
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143604
TI  - Biomonitoring exposure to metal compounds with carcinogenic properties.
AB  - Several metals such as arsenic, beryllium, chromium and nickel are carcinogenic
      to man when they occur in certain well-defined physicochemical forms. The
      carcinogenic potential of these metals is linked to their mutagenic properties.
      The determination of the metal or possibly of its metabolites in biological media
      and the cytogenetic examination of somatic cells are two methods that can
      currently be used to monitor exposure of populations at risk. Due to the use of
      inappropriate methodology, the value of the positive cytogenetic results
      published so far appears questionable. By contrast, the concentrations of metals
      in blood, urine, or other biological materials can be determined with accurate
      and precise methods. Although it does not permit a direct assessment of the
      carcinogenic risk, this approach is currently the most suitable for monitoring
      exposed populations.

PMID- 8143605
TI  - The HPRT short-term assay in monitoring individuals exposed to genotoxic agents.
AB  - This paper reviews several monitoring studies where the short-term HPRT assay has
      been applied. The original method uses autoradiography to detect 3H-thymidine
      incorporation in variant cells that have undergone DNA synthesis; the
      bromodeoxyuridine modification employs this thymidine analog and fluorescence
      plus Giemsa staining. The studies discussed here were accomplished with either of
      these methods. methods. Exposures analyzed include radiation and chemotherapy as
      medical treatments and accidental exposures to radiation; these studies have been
      useful in the validation of the assay because radiation and anticancer drugs are
      well-known mutagens. Other potential mutagens such as environmental arsenic and a
      parasitic infection and praziquantel, used for its treatment, have also been
      monitored for hprt locus mutation. An overview of the results obtained with
      different agents and routes of exposure is presented here as well as some
      methodological aspects for the optimization of the assay for monitoring studies.

PMID- 8143606
TI  - Micronucleus assay in lymphocytes as a tool to biomonitor human exposure to
      aneuploidogens and clastogens.
AB  - The analysis of micronuclei (MN) in cultured human lymphocytes is, in principle,
      able to detect exposure to clastogens and aneuploidogens alike. There is,
      however, no clear evidence from human biomonitoring studies or animal experiments
      showing that in vivo exposure of resting lymphocytes to an aneuploidogen could
      actually be expressed as MN in cultured lymphocytes. In vitro, a pulse treatment
      of human lymphocytes with vinblastine, an aneuploidogen, did result in MN
      induction even if performed before mitogen stimulation, although a much more
      pronounced effect was obtained in actively dividing lymphocyte cultures. On the
      other hand, it is probable that a considerable portion of "spontaneous" MN
      contain whole chromosomes, their contribution increasing with age. It also seems
      that cytochalasin B, used for the identification of second cell cycle interphase
      cells in the MN assay, is able to slightly increase the level of MN with whole
      chromosomes. If MN harboring chromosome fragments represent a minority of the
      total MN frequency, there may be difficulties in detecting a weak effect in this
      fraction of MN against the background of MN with whole chromosomes. This would
      reduce the sensitivity of the assay in detecting clastogens, unless MN with whole
      chromosomes and chromosome fragments are distinguished from each other. That a
      problem may exist in sensitivity is suggested by the difficulty in demonstrating
      MN induction by smoking, an exposure capable of inducing chromosome aberrations.
      The sensitivity of the lymphocyte MN assay could be increased by detecting
      kinetochore or centromere in MN, or by automation, allowing more cells to be
      analyzed.

PMID- 8143607
TI  - Analysis of cigarette-smoke-induced DNA adducts by butanol extraction and
      nuclease P1-enhanced 32P-postlabeling in human lymphocytes and granulocytes.
AB  - In an earlier study, we analyzed the aromatic DNA adducts separated from
      lymphocytes and granulocytes of smokers and nonsmokers using the nuclease P1
      enhanced 32P-postlabeling assay. Here we compare the butanol extraction and
      nuclease P1-enhanced procedure on the same kind of samples. The DNA adducts of 42
      per 10(8) nucleotides from smokers' lymphocytes were statistically higher (p <
      0.05) than those of 11 from nonsmokers', when analyzed by the nuclease P1
      treatment, but not by the 1-butanol extraction. The radioactivity obtained from
      the DNA digests on the TLC plates was lower in butanol-treated DNA samples when
      compared to those of nuclease P1 digestion. Lymphocytes appear to be a suitable
      test tissue for determining aromatic carcinogen exposure when detecting smoking
      related DNA adducts by the nuclease P1-enhanced 32P-postlabeling analysis.

PMID- 8143608
TI  - Multiple end point procedure to evaluate risk from pesticides.
AB  - Because of the potential environmental impact of pesticides and the large
      population potentially exposed, the effects of chronic exposure to pesticides
      need to be determined. Mutagenicity studies have been used to identify specific
      agents as potential carcinogens or other human health hazards. However, short
      term tests are only theoretically correlated to carcinogenesis because their end
      points can measure only the genotoxic potential of chemicals, i.e., their
      activities as initiating agents in multistep carcinogenesis. The objective of our
      research presented here is to provide a comprehensive examination of the
      mechanism of toxicity of a series of pesticides. These are substances for which
      toxicity, at both the genetic and metabolic level, has not been adequately
      described. Preliminary results on a broad series of compounds belonging to
      different biological classes (herbicide, insecticide, fungicide) seem to indicate
      that pesticides are toxic but are poor initiating agents, as shown by negative or
      weak positive results on different genetic end points (gene mutations, DNA
      effects, and chromosome aberrations in vitro and in vivo). Immunochemical and
      biochemical studies, however, seem to indicate the cocarcinogenic and promoting
      potential of these chemicals. As an example, the genotoxic and biochemical
      effects induced by Fenarimol (a fungicide) are discussed. The results reported
      stress the importance of identifying chemicals that act at different levels of
      the multistep carcinogenesis process to ascertain the risk associated with
      exposure.

PMID- 8143609
TI  - Noninvasive methods for measuring DNA alkylation in experimental animals and
      humans.
AB  - Alkylpurines are liberated from alkylated DNA by glycosylase repair enzymes and,
      in most cases, excreted in urine without further metabolism. This phenomenon
      forms the basis of noninvasive methods to measure DNA alkylation in vivo. In the
      case of methyl adducts, such as 7-methylguanine (7-MeGua), natural backgrounds
      exist due to RNA turnover. However, deuterated (d3) methylating agents or
      precursors give rise to d3-7-MeGua and d3-3-methyladenine (3-MeAde), which can be
      readily quantitated using gas chromatography-mass spectrometry (GC-MS). A
      deuterated probe drug, such as d6-aminopyrine, can be used to measure endogenous
      nitrosation levels in experimental animals. In contrast, for higher alkyl
      homologues of alkylpurines, natural backgrounds are low or nonexistent and can be
      directly measured by GC-MS using stable isotope labeled internal standards. For
      example, increased levels of urinary 3-ethyladenine were observed in cigarette
      smokers. Due to recent advances in analytical methodology, notably immunoaffinity
      cleanup of urine, measurements of excreted DNA adducts can be used in studies in
      human populations exposed to low levels of alkylating carcinogens.

PMID- 8143610
TI  - Monitoring genotoxic exposure in uranium mines.
AB  - Recent data from deep uranium mines in Czechoslovakia indicated that mines are
      exposed to other mutagenic factors in addition to radon daughter products.
      Mycotoxins were identified as a possible source of mutagens in these mines.
      Mycotoxins were examined in 38 samples from mines and in throat swabs taken from
      116 miners and 78 controls. The following mycotoxins were identified from mines
      samples: aflatoxins B1 and G1, citrinin, citreoviridin, mycophenolic acid, and
      sterigmatocystin. Some mold strains isolated from mines and throat swabs were
      investigated for mutagenic activity by the SOS chromotest and Salmonella assay
      with strains TA100 and TA98. Mutagenicity was observed, especially with metabolic
      activation in vitro. These data suggest that mycotoxins produced by molds in
      uranium mines are a new genotoxic factor for uranium miners.

PMID- 8143611
TI  - A study of sister chromatid exchange and somatic cell mutation in hospital
      workers exposed to ethylene oxide.
AB  - To investigate the risks of exposure to ethylene oxide (EO) at current
      permissible levels and at past higher levels, an inception cohort of sterilizer
      operators and supervisors from the Central Processing Department (CPD),
      respiratory therapists, and engineers exposed to EO were identified at the
      McMaster University Medical Centre. A comparison group from Nutrition Services
      (NUTR) were matched with the CPD workers on the basis of sex, age, and smoking
      habit. The present report is based on genetic test results for the 94 CPD and
      matched NUTR workers only. Statistical analysis based on the mean SCE frequency
      in the top 5, top 10, and all cells (50 cells scored per individual) and high
      frequency cells (HFC) based on the 95th percentile for nonsmoking control
      subjects showed a direct association with current smoking but not with EO
      exposure. Similarly, statistical analysis of the somatic cell mutation (SCMT)
      variant frequencies did not demonstrate an association with EO exposure, nor with
      smoking. Regression analysis indicated that sex was the only other covariate that
      significantly affected SCE. Age was weakly associated with SCMT. A statistically
      significant interaction between occupational exposure and smoking habits was
      observed only for the mean SCE frequency of the top 5 and top 10 cells when the
      11 current CPD/NUTR pairs were not included. Thus, this interaction should be
      interpreted with caution.

PMID- 8143612
TI  - Global problems from exposure to asbestos.
AB  - Considerable human-derived data the health consequences of asbestos exposure are
      available. Usually, less information is available from laboratory models of
      asbestos-related health effects. Animal data mirror the experience in man, and
      cellular studies help in to understand the mechanistic changes related to
      asbestos. Although it is clearly carcinogenic, asbestos has shown much
      variability when examined for its mutagenic activity. Asbestos, a commercial term
      referring to a family of six naturally occurring mineral fibers, has been widely
      used around the world. Disease has been recognized into the last century, and at
      this time every occupational group that has been examined for possible asbestos
      related disease has demonstrated it. Disease associated with asbestos makes no
      distinction based on race or geography, and wherever asbestos is handled it
      produces disease. With shifting global commercial patterns, disease patterns can
      be expected to shift also.

PMID- 8143613
TI  - Mutagenesis after cancer therapy.
AB  - A subset of Hodgkin's disease (HD) and breast cancer patients have been reported
      to have elevated hprt mutant frequencies in peripheral blood lymphocytes after
      cessation of therapy. A subset of these patients are also known to develop second
      therapy-related malignancies. Therefore, it is clearly important to determine if
      these elevations in mutant frequency represent true, persistently elevated
      mutation frequencies. As a follow-up to our study of patients previously treated
      for HD, we recruited for a prospective study six previously treated HD patients
      and five patients who had been treated for squamous cell carcinoma of the head
      and neck. These individuals were studied several times over a 6-7 months. The
      results confirmed that a subset of patients have persistently high mutant
      frequencies when compared to 71 previously studied controls. The study was
      designed to determine if the elevated mutant frequencies of treated patients
      represented independent mutations or resulted from the in vivo expansion of
      single mutant cells. We used the polymerase chain reaction to examine DNA single
      strand conformation polymorphisms at the T-cell receptor-gamma locus of
      individual mutant clones. This analysis showed that 20.1% of the mutants from
      Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma
      patients were siblings. The sibling mutants generally did not persist over time.
      However, one patient had one mutant clone that persisted, but slowly decreased in
      prevalence over a 7 month sampling period. The data demonstrate that treatments
      for cancer result in persistently elevated mutation frequencies at the hprt locus
      in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143614
TI  - K-ras oncogene codon 12 point mutations in testicular cancer.
AB  - A significant association between N-ras oncogene activating point mutations and
      testicular cancer has recently been reported. We have studied DNA samples from
      the blood and fresh tumor tissues of 17 Norwegian testicular cancer patients (11
      seminomas/6 nonseminomas). Point mutations in K-ras-2 and N-ras exons 1 and 2
      were studied by denaturing gradient gel electrophoresis (DGGE) and by
      oligonucleotide hybridization. No N-ras mutations were detected in these tumor
      samples, but two K-ras-2 exon 1 mutations were found in two of the seminoma
      tumors (stage I and II tumors) using the DGGE technique. The mutations were
      confirmed by dot blotting and oligonucleotide hybridization and identified as a G
      ->T and a G-->A point mutation in K-ras-2 codon 12, leading to a valine and a
      serine substitution, respectively. All the white blood cell DNAs were negative.
      As a positive control for DGGE screening, we ran two plasmid constructs carrying
      human N-ras exon 2 sequences with mutations. To study the role of ras gene
      activation in testicular cancer, a larger tumor sample population will be
      investigated.

PMID- 8143615
TI  - Interaction between smoking and asbestos in human lung adenocarcinoma: role of K
      ras mutations.
AB  - To investigate the role of tobacco smoking and asbestos fibers in the etiology of
      human lung cancer, we examined the activating point mutations in the K-ras
      oncogene in DNA samples from 49 patients. Mutations were found more often in
      tissue from adenocarcinomas (12/21) than in tissue from tumors other than
      nonadenocarcinomas of the lung (3/28). Among the adenocarcinoma patients,
      asbestos exposure was predictive of K-ras mutation (odds ratio, 4.9; 95%
      confidence interval, 0.7-34.3); in patients with other types of lung cancer, the
      relation appeared to be an inverse one, but the numbers were small. The
      proportion of heavy smokers (over 50 pack-years) was 60% among people with K-ras
      mutations and 35% among the K-ras-negative subjects, suggesting that smoking
      causes K-ras mutations. If mutations in K-ras genes are caused by smoking,
      asbestos would act as a promoting agent by conferring selective growth conditions
      for clonal expansion on these mutated cells. Asbestos may favor recruitment of
      (initiated) K-ras mutation-positive cells in the multistage process of
      carcinogenesis by stimulating cellular growth.

PMID- 8143616
TI  - Somatic cell gene mutations in humans: biomarkers for genotoxicity.
AB  - Somatic cell gene mutations arising in vivo in humans provide biomarkers for
      genotoxicity. Four assays, each measuring changes in a different "recorder" gene,
      are available for detecting mutations of the hemoglobin (Hb) and glycophorin A
      (gpa) genes in red blood cells and the hypoxanthine-guanine
      phosphoribosyltransferase (hprt) and HLA genes in T-lymphocytes. Mean adult
      background mutant frequencies have been established; i.e., approximately 4 x 10(
      8) (Hb), 5-10 x 10(-6) (hprt), 10-20 x 10(-6) (gpa) and 30 x 10(-6) (HLA). All
      the assays have now been used in studies of individuals exposed to physical
      and/or chemical genotoxic agents, and all have shown elevated values following
      exposures; examples are presented. In addition to quantitation, the lymphocyte
      assays allow molecular analyses of in vivo mutations, the definition of
      background and induced mutational spectra, and the search for unique changes for
      characterizing specific mutagens. The HPRT system currently has the largest
      database in this regard. Approximately 15% of adult background hprt mutations are
      due to gross structural alterations (primarily deletions) having random
      breakpoints; 85% result from "point" changes detected only by sequencing. In
      contrast, a specific intragenic deletion due to DNA cleavage at specific sites
      characterizes fetal hprt mutations, implicating a developmental mistake in their
      genesis. (This kind of developmental mistake in other genes is frequently
      observed in lymphoid malignancies.) Mutational spectra are just beginning to be
      defined for induced hprt mutations, e.g., ionizing radiation produces large
      deletions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143617
TI  - Chemical interaction: enhancement and inhibition of clastogenicity.
AB  - Most environmental exposures involve concurrent or sequential exposure to
      multiple chemicals in air, water, and food. Interactive effects in carcinogenesis
      have been described for certain combinations of agents. They are described in
      terms of enhancement or inhibition of carcinogenesis. Enhancement effects have
      been documented for cigarette smoking in combination with exposure to asbestos,
      radon, alcohol, or other exposures. A variety of inhibitors of carcinogenesis
      have also been described. They are classified into agents preventing formation of
      carcinogens; blocking agents; and suppressing agents. Assessment of risk from
      exposure to multiple agents can be derived either from epidemiological studies in
      relation to actual exposure or from laboratory studies after controlled exposure
      to different agents. Prediction of how toxic components of mixtures will interact
      should be based on an understanding of the mechanisms of such interactions.
      Compounds may interact chemically, yielding new toxic components or causing a
      change in the biological availability of the existing components or metabolites.
      In humans, great individual variability in response is to be expected because of
      genetic heterogeneity or acquired host susceptibility factors. Interaction is
      thus a key component in the risk assessment process. In this paper, the
      definition of interaction and the theoretical basis for different types of
      interaction in cancer causation are reviewed. Epidemiological and experimental
      studies showing interactive effects of two chemical carcinogens are also
      presented.

PMID- 8143618
TI  - Molecular analysis of mutations induced at the hisD3052 allele of Salmonella by
      single chemicals and complex mixtures.
AB  - More single chemicals and complex environmental mixtures have been evaluated for
      mutagenicity at the hisD3052 allele of Salmonella, primarily in strain TA98, than
      in any other mutation assay. The development of colony probe hybridization
      procedures and the application of the polymerase chain reaction and direct DNA
      sequencing has permitted rapid molecular access to this allele. We discuss these
      techniques and the resulting mutation spectra that have been induced by a variety
      of environmental mutagens and complex mixtures. A common GC or CG deletion within
      a hot-spot region of the sequence dominates most of the spectra. In addition to
      this two-base deletion, we have recovered about 200 other types of mutations
      within the 72-base target for reversion of the hisD3052 allele. These include a
      variety of deletions (as large as 35 bases), duplications (as large as 46 bases),
      and complex mutations involving base substitutions. The quasipalindromic nature
      of the target sequence and its potential to form DNA secondary structures and
      slippage mismatches appear to be an important basis for the mutability of this
      allele.

PMID- 8143619
TI  - Mutagenicity testing of 9-N-substituted adenines and their N-oxidation products.
AB  - Adenine together with certain 9-N-substituted derivatives such as 9-methyl, 9
      benzyl, 9-benzhydryl, and 9-trityl were tested against Salmonella typhimurium
      strains TA97, TA98, and TA100 in the absence and presence of rat hepatic S9
      prepared from Aroclor 1254 pretreated rats. All compounds were positive toward
      TA98 in the presence of the metabolic activating system, whereas they all lacked
      mutagenic activity in the absence of S9, and toward TA97 and TA100 with or
      without S9 when tested at 100 ng/plate. A similar pattern was observed for the
      corresponding 1-N-oxides. 6-Hydroxylaminopurine was not mutagenic toward TA100 at
      100 ng/plate, whereas it was toxic toward TA97 and TA98 at this level. When
      tested at 1 ng/plate, hydroxylaminopurine was still toxic to TA98 but produced
      twice the spontaneous reversion rate to TA97 without metabolic activation.
      Surprisingly, 9-methyl-6-hydroxylaminopurine was only active toward TA98 in the
      presence of S9, whereas 9-benzyl-6-hydroxylaminopurine was highly active toward
      TA97 and TA100 in the absence of S9 and even more active in the presence of S9.
      This compound was inactive toward TA98 in the absence of S9. The results
      generally support the concept that nuclear N-oxidation of aminoazaheterocycles is
      a detoxication process, whereas N-hydroxylation of the exo amino group is a
      toxication reaction.

PMID- 8143620
TI  - Quantitative and molecular analyses of genetic risk: a study with ionizing
      radiation.
AB  - Mammalian cells in culture have been used to study the genetic effects of
      physical and chemical agents. We have used Chinese hamster ovary (CHO) cells,
      clone K1-BH4, to quantify mutations at the X-linked, large (35 kb) hypoxanthine
      guanine phosphoribosyltransferase (hprt) locus (the CHO/HPRT assay) induced by
      environmental agents. By transfecting an hprt-deletion mutant CHO cell line with
      the plasmid vector pSV2gpt, we isolated a transformant, AS52. AS52 cells carry a
      single functional copy of an autosomal, small (456 bp) xanthine-guanine
      phosphoribosyltransferase (gpt) gene (the bacterial equivalent of the mammalian
      hprt gene; AS52/GPT assay). We found that ionizing radiations such as X-rays and
      neutrons and oxidative genotoxic chemicals such as Adriamycin, bleomycin,
      hydrogen peroxide, and potassium superoxide are much more mutagenic to the gpt
      gene in AS52 cells than to the hprt locus in K1-BH4 cells. The hypermutability of
      the gpt gene probably results from a higher recovery of multilocus deletion
      mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced
      mutants. These results demonstrate that the use of the hprt locus alone could
      lead to an underestimate of the genetic risk of these agents. Analyses of the
      mutation spectrum using a polymerase chain reaction-based deletion screening and
      DNA sequencing procedure showed that a high proportion of HPRT- and GPT- mutants
      induced by X-rays carry deletion mutations. Thus, both the mutant frequency and
      mutation spectrum need to be considered in assessing the genetic risk of ionizing
      radiation and oxidative genotoxic chemicals.

PMID- 8143621
TI  - Quantification and molecular characterization of hprt mutants of human T
      lymphocytes.
AB  - Somatic mutations have been implicated as critical early events in
      carcinogenesis. Point mutations, deletions, and translocation events have been
      shown to activate oncogenes or inactivate suppressor oncogenes. In human
      population monitoring, quantitative analysis of mutation events that affect gene
      function is limited to those genes whose cellular phenotypes can be identified by
      selection procedures and to those tissues (like blood) that are accessible for
      analysis. In an effort to determine the frequency and types of mutations that can
      be detected at the hypoxanthine guanine phosphoribosyltransferase (hprt) gene, we
      have used the T-cell cloning assay and have developed a strategy to propagate
      mutants and screen for point mutations and breakage events. Early in the clonal
      expansion of mutants, 1-2 x 10(4) cells are prepared as a crude cell lysate, and
      a sample is analyzed using the multiplex polymerase chain reaction (PCR). Those
      mutants that yield altered DNA fragments are then expanded for Southern blot
      hybridization, PCR, flanking probe isolation, and DNA sequencing. To date we have
      found presumed point mutations, intragenic deletions, and deletions that extend
      outside of the hprt gene. By analyzing mutations in selectable, nonessential gene
      markers, it should be possible to understand mechanisms of both spontaneous and
      induced genetic damage. An association of these specific genetic events with
      human diseases and the evaluation of the ability of environmental chemicals to
      induce these specific types of mutations will lead to a rational basis for
      evaluating risks from various chemical exposures.

PMID- 8143622
TI  - Mechanisms for induction of mutations and chromosome alterations.
AB  - Genotoxic agents induce chromosomal alterations, such as aberrations,
      micronuclei, and sister chromatid exchanges as well as mutations both in vivo and
      in vitro. Ionizing radiation and typical radiomimmetic agents such as bleomycin
      are very efficient inducers of chromosomal aberrations. The type of aberrations
      induced by these agents are cell-cycle dependent, i.e., chromosome type in pre
      replication stages and chromatid type in post-replication stages of the cell
      cycle. Under optimal DNA repair conditions, DNA double-strand breaks (DSBs)
      appear to be the most important lesion responsible for the production of
      aberrations. In human lymphocytes, fast-repairing DSBs lead to exchange-type
      aberrations. The fact that the dose-response curves for induction of exchange
      aberrations induced by ionizing radiation are similar in vitro and in vivo allows
      one to use the yield of induced aberrations to estimate absorbed radiation dose
      in the case of accidents. In this respect, frequencies of translocations detected
      by the chromosome painting technique appear to be more sensitive. Mutations do
      not express immediately after exposure and require an expression time before they
      can be detected. In humans, it is estimated that for the mutations induced in
      bone marrow, it takes about 2 months for them to express and to be detected in
      peripheral blood lymphocytes. Hence, frequency of mutations is of limited value
      for estimating radiation doses immediately after an accident. This holds true for
      chemical exposure as well.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143623
TI  - A perspective on nonmutagenic mechanisms in carcinogenesis.
AB  - Although there is compelling evidence for multiple mutagenic events in the
      induction of cancers, there is also substantial evidence in support of
      nonmutagenic mechanisms. It is proposed that the genetic basis of noninduced or
      spontaneous tumors, as well as cancers induced by nonmutagens, involves heritable
      changes in the regulation of gene expression.

PMID- 8143624
TI  - Molecular mechanisms in cancer induction and prevention.
AB  - Chemical and physical carcinogens, present in our environment and encountered in
      a variety of occupations, produce damage to DNA. X-rays produced direct
      ionizations and indirect hydroxyl radical attack. UV light in the short
      wavelength is specifically absorbed by unsaturated bonds in DNA, RNA, and
      proteins. There are a number of genetic sites that are specifically affected by
      environmental agents, and an increased sensitivity is found in certain genetic
      diseases. The development of a fully malignant tumor involves the activation or
      altered expression of oncogenes or the inactivation of tumor-suppressor genes
      that control normal cellular development. Mutations in the p53 tumor-suppressor
      gene are common in diverse types of cancer and could perhaps provide clues to the
      etiology of some cancers and to the effect of various environmental and
      occupational carcinogens in cancer development. The fact that environmental
      factors are involved to a great extent in cancer suggest that cancer may be
      preventable. Experimental as well as epidemiological data indicate that a variety
      of nutritional factors can act as anticarcinogens and inhibit the process of
      cancer development and reduce cancer risk. The interaction of cells with a number
      of environmental and occupational genotoxic substances such as X-rays, UV light,
      and a variety of chemicals including ozone results in an enhanced generation of
      free oxygen radicals and in modified pro-oxidant states. A number of nutritional
      factors such as vitamins A, C, E, beta-carotene, and micronutrients such as
      selenium act as antioxidants and anticarcinogens. Certain hormones such as
      thyroid hormones enhance oxidative processes and act as a co-transforming factor
      in carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143625
TI  - Antimutagenic and mutagenic potentials of Chinese radish.
AB  - The edible part of fresh Chinese radish was chopped into small pieces,
      lyophilized, and then extracted sequentially with hexane, chloroform, and
      methanol. The solvent in each fraction was removed by evaporation under reduced
      pressure at 50-55 degrees C, and the residue was dissolved in dimethylsufoxide
      just before being tested for antimutagenicity as well as mutagenicity using the
      Salmonella/mammalian microsome mutagenicity test. We found that none of the three
      fractions exhibited any mutagenicity toward S. typhimurium strains TA98 and TA100
      when tested either in the presence or absence of S-9 mix. Interestingly, however,
      hexane and chloroform extracts could strongly inhibit the mutagenicities of both
      direct mutagens (e.g., 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide and sodium
      azide) and indirect mutagens (e.g., aflatoxin B1). In contrast, however, these
      two fractions did not inhibit the mutagenicity of benzo[a]pyrene, which is also
      an indirect mutagen. Both hexane and chloroform extracts could also markedly
      inhibit the activities of rat liver aniline hydroxylase and aminopyrine
      demethylase. The methanol fraction could inhibit neither the mutagenicities of
      direct or indirect mutagens tested nor the activities of those two rat liver
      enzymes. Results of the present study demonstrate that Chinese radish may not
      contain any mutagenic compound but does contain some nonpolar compounds with
      antimutagenic activity toward both direct and indirect mutagens. In addition, the
      antimutagenic activity toward aflatoxin B1 may be partly due to the inhibition of
      enzymes necessary for activation of this mutagen.

PMID- 8143626
TI  - Genetic alterations in carcinogenesis and chemoprevention.
AB  - Laboratory and clinical studies suggest that genetic change is intrinsically
      involved in the development of cancer and that this change occurs in humans
      throughout carcinogenesis, in both early and late stages. Therefore, the
      quantification of the level of genetic change in human epithelial tissues may
      serve as a marker for cancer risk. The micronucleus test has been used to
      quantify the level of site-specific chromosomal breakage occurring in epithelial
      tissues of individuals at elevated risk for cancer. These studies include
      individuals exposed to carcinogens, patients who have chromosome-breakage
      syndromes, and individuals with premalignant lesions. As a counterpart to this
      approach, the assay has been used to study the suppression of this breakage with
      chemopreventive agents, some of which occur naturally in the diet. These agents
      include beta-carotene, retinyl palmitate, 13-cis-retinoic acid, riboflavin,
      canthaxanthin, and folic acid. Not all of these agents were effective. The
      success of the treatment depended on both the agent being used and the population
      being studied. The results of these studies suggest that successful intervention
      with chemopreventive agents will depend on tailoring treatment regimens to
      specific populations. The micronucleus test can be used along with other
      biological end points to obtain an early indication of the efficacy of
      chemopreventive agents in altering biological changes associated with
      carcinogenesis in tissues of high-risk individuals.

PMID- 8143627
TI  - Genetic effects of dioxins in the spot test with mice.
AB  - More than any other environmental chemicals, dioxins have been in the limelight
      of public interest for about 10 years. In addition to carcinogenicity, genetic
      risk is a cause for concern. Mutagenicity tests performed so far do not give a
      clear picture. The mutagenic potential of dioxins has to be considered weak or
      absent. Therefore, it seemed profitable to investigate comutagenicity and co
      recombinogenicity of dioxins more thoroughly. The only useful method for
      investigating comutagenicity and co-recombinogenicity of dioxins in vivo is the
      spot test with mice. In this test system, a number of cocarcinogens and tumor
      promoters have shown comutagenic or co-recombinogenic effects. In the present
      study, tetrachlorodibenzo-p-dioxin (TCDD) and two environmental dioxin mixtures
      [pentachlorodibenzodioxin (PCDD) 1 and 2] were tested for genetic activity. Given
      alone, no mutagenic or recombinogenic effects could be observed. In combination
      with the carcinogenic mutagen ethyl nitrosourea (ENU) at concentrations of 128
      micrograms/kg for PCCD 2, 314 micrograms/kg for PCDD 1, and 3 micrograms/kg for
      TCDD, a doubling of the genetic effectiveness of ENU was observed. The genetic
      risk can roughly be considered as 1:0.02 for TCDD:PCDD 2 and 1:0.01 for TCDD:PCDD
      1. While PCDD 1 and 2 seem to enhance the mutagenic as well as the recombinogenic
      potential of ENU, TCDD showed mainly co-recombinogenic and antimutagenic
      activity. This characteristic indicates that TCDD is mainly a tumor promoter.

PMID- 8143628
TI  - Genetic effects from exposure to hazardous agents.
AB  - Mammalian germ cell stages exhibit differences in DNA synthesis activity,
      capability to repair DNA damage, and chromosome-associated proteins. The
      sensitivity to mutation induction may be influenced by such factors as the
      accessibility of DNA to chemical mutagens, the interval between DNA damage
      induction and the next round of DNA replication, and the repair of DNA damage.
      Such qualitative and quantitative differences indicate the complexities of
      mutation induction in vivo and emphasize that no single in vitro test system can
      adequately represent the in vivo situation. Therefore, germ-cell mutagenesis in
      humans can most adequately be represented by an in vivo mammalian germ-cell test
      system. Information regarding the mechanisms of mutation induction in germ cells
      of the mouse, appropriate mutation test systems available in the mouse, as well
      as principles of chemical mutagenesis in the mouse and their implications for an
      adequate human genetic risk estimation will be discussed.

PMID- 8143629
TI  - Maternal factors, medications, and drug exposure in congenital limb reduction
      defects.
AB  - As part of an ongoing study on all limb reduction defects occurring among
      1,213,913 consecutive live births in the province of British Columbia, Canada,
      during 1952-1984, cases with documented maternal drug exposure and chronic
      maternal diseases were analyzed separately. This population-based study was made
      possible through the existence of an ongoing Health Surveillance Registry, which
      documents all infants born with congenital, genetic, or chronically handicapping
      conditions in the province of British Columbia. Strict rules of confidentiality
      are obeyed. For this part of the analysis of limb reduction defects, cases with
      documented maternal illness, drug abuse, and exposure to environmental hazards
      early in pregnancy were analyzed as a separate group to identify specific,
      recurring patterns of anomalies. A total of 51 cases with possibly related
      maternal factors were identified. Among them were five cases with maternal
      epilepsy, four cases with documented maternal diabetes, and three cases with
      uterine anomalies. Three infants, all born in 1962, had documented thalidomide
      exposure. It is rarely possible to identify particular teratogenic factors or
      specific maternal factors as etiologically related to the pattern of limb
      reduction defects or a spectrum of congenital malformations. Exposure to
      environmental factors during pregnancy is not reliably registered and can thus
      only occasionally be ascertained in retrospective studies. This means that very
      large numbers of cases and cross-referencing to other family members are required
      to assess whether a potential teratogen is related to limb defects or not.

PMID- 8143630
TI  - Metabolism of 2-aminofluorene by human polymorphonuclear leukocytes: more
      evidence for the association between inflammation and cancer.
AB  - Recent investigations have demonstrated the ability of leukocytes to metabolize
      promutagens or procarcinogens into their genotoxic forms. As a possible
      explanation for the association between inflammation and cancer, we and others
      have hypothesized that local accumulations of leukocytes could take up nearby
      promutagens, metabolize them, and release genotoxic agents that may cause damage
      in the surrounding tissue. Using a modified, two-step preincubation protocol with
      Salmonella, we have tested this hypothesis. We have shown that total human
      peripheral blood leukocytes, cultured in the presence of 2-aminofluorene for 18
      hr, can metabolize 2-aminofluorene into agents mutagenic to Salmonella
      typhimurium strain TA98. Furthermore, experiments in which polymorphonuclear
      leukocytes were separated from mononuclear leukocytes demonstrated that the PMNs
      metabolized 2-aminofluorene to a much greater extent than the MNs.

PMID- 8143631
TI  - Birthweight below the tenth percentile: the relative and attributable risks of
      maternal tobacco consumption and other factors.
AB  - Analysis of 7776 singleton births defined a cohort of babies with birthweight
      below the 10th percentile after adjusting for gestational age and sex. The
      relative risk of a baby being small for gestational age in respect to a number of
      factors, such as parental anthropometry, demographic factors, behavior patterns
      (tobacco, cannabis, alcohol, and caffeine consumption), maternal pathology, and
      fetal abnormality, was calculated. The highest relative risks are associated with
      severe antepartum hemorrhage, severe pre-eclampsia, and severe fetal abnormality.
      As these are relatively rare events, a more accurate calculation of overall risk
      to the population as opposed to the individual can be obtained by studying the
      percent attributable risk of each of the factors. This demonstrates that maternal
      tobacco consumption is the major environmental risk factor in our population.

PMID- 8143632
TI  - Epidemiological studies in monitoring reproductive effects.
AB  - The possible hazards of occupational exposure on the reproductive health of
      workers is of great interest. In this review, epidemiological study designs
      suitable for reproductive studies and sources of outcome and exposure data are
      described with a few examples. Studies have been conducted on hormonal changes,
      semen quality, fertility, and various outcomes of pregnancy, e.g., spontaneous
      abortion, congenital malformations, perinatal mortality, birth weight, and health
      and development of the children. Also, sex distribution of children has been
      investigated as a possible risk indicator in some recent studies. In
      epidemiological studies, retrospective or prospective cohort design, case
      referent and nested case referent designs have been used. The validity of
      epidemiological studies depend on reliable data on the health effect and the
      exposure. The registers on congenital malformations and on births and other
      outcomes of pregnancy are useful sources of data for epidemiological studies. The
      coverage of the register and the accuracy of its contents should be known if the
      register is used for research. Personal interview of the worker is an important
      source of information, although recall problems may weaken the quality of the
      data. The reliability of the answers may be increased by using a few
      complementary questions on possible medical confirmation of the event. If both
      the interview and register data are available, the reliability of the information
      increases, the same concerns exposure information also. Examples of some
      conducted studies are given.

PMID- 8143633
TI  - Primary and secondary risk factors for birth defects.
AB  - Birth defects may be inherited in the germ line or may result primarily from a
      wide spectrum of predictable physical, chemical, and infectious processes that
      can operate in the mother, the father, or in the zygote. The systematic
      consideration of these mechanisms can lead to a fresh awareness of risk and
      possible strategies toward recognizing and avoiding such risks. Birth defects
      also depend heavily on secondary factors that may even be of greater concern than
      any single primary insult because they may simultaneously affect the consequences
      of more than one primary exposure. Under the influence of secondary factors, the
      frequency, timing, and intensity of developmental deficiencies can be quite
      varied. It is particularly interesting that expression can be delayed until quite
      late in life, and deficiencies may occur or be expressed only in response to the
      appropriate environmental stress or functional demand. Any discussion of
      teratogenic mechanisms, therefore, is not complete without taking into account
      the important concept of co-teratogenesis, or the operation of secondary risk
      mechanisms. The principle of secondary risk or co-teratogenesis has been
      demonstrated by means of enhancement of radiation-induced terata by the
      administration of drugs that inhibit DNA repair. An example of late-onset
      expression of prenatal damage was illustrated with postnatal retinal degeneration
      occurring after prenatal damage to the developing retina. It is suggested that a
      systematic consideration of primary and secondary risk mechanisms can lead to a
      better understanding of the problem of birth defects.

PMID- 8143634
TI  - Risk and benefit evaluation in development of pharmaceutical products.
AB  - Pharmaceutical products are intended to cure disease, reduce pain and suffering,
      prolong life, and correct metabolic deficits in patients. However, the potential
      patient population is intrinsically genetically heterogenous, and this factor
      complicates the evaluation of data on all aspects of safety evaluation of new
      drugs. Often the genetic heterogeneity is related to drug metabolizing capacity,
      but recent evidence suggests that heterogeneity in repair capacity as well as
      structural integrity of the chromatin (fragile X) have been shown to be relevant.
      Because drugs are biologically active and may have more than one type of effect,
      the evaluation of a large number of parameters is necessary in arriving at a
      rational estimate of potential risk. In this paper, several specific examples of
      risk assessments and some generic genotoxicity questions that are recurrent,
      including the question of the relevance of in vitro chromosomal aberration
      induction at high dose/sampling time, are raised. Other examples of the kinds of
      concerns from the safety evaluation of U-48753E, U-54461, and U-68,553B are
      discussed. The drug U-48753E was discovered to be slightly mutagenic in the AS52
      assay, and significant efforts were expended in evaluation of the metabolism
      based generation of a reactive intermediate. The drug U-54,461 was shown to be
      capable of breaking chromosomes in vitro but extensive in vivo data as well as a
      variety of other studies served to reduce the level of concern
      substantially.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143635
TI  - Human health risks due to consumption of chemically contaminated fishery
      products.
AB  - A small proportion of fishery products contaminated with appreciable amounts of
      potentially hazardous inorganic and organic contaminants from natural and
      environmental sources seem to pose the greatest potential for toxicity to
      consumers of fishery products in the United States. Health risks due to chemicals
      (e.g., modest changes in the overall risk of cancer, subtle deficits of
      neurological development in fetuses and children) are difficult to measure
      directly in people exposed to low levels. Immunocompetence may increase cancer
      risk. Inferences about the potential magnitude of these problems must be based on
      the levels of specific chemical present, observations of human populations and
      experimental animals exposed to relatively high doses, and theories about the
      likely mechanisms of action of specific intoxicants and the population
      distribution of sensitivity of human exposure. Lognormal distributions were found
      to provide good descriptions of the pattern of variation of contaminant
      concentrations among different species and geographic areas; this variability
      offers a solution for reduction of exposure through restricting harvest of
      aquatic animals from certain sites and by excluding certain species. Available
      information suggest that risks are not generally of high magnitude; nevertheless,
      their control will significantly improve public health.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8143636
TI  - Abnormal chromosome repair and risk of developing cancer.
AB  - Several scientists have proposed that DNA repair deficiencies and the induction
      of a mutator phenotype are responsible for the generation of multiple mutagenic
      alterations in cancer cells. I propose that exposure to environmental carcinogens
      can induce DNA lesions, elicit infidelity of DNA repair, and cause the
      instability phenomenon and the subsequent consequences. Using cell lines derived
      from mammary glands of irradiated mice, my laboratory conducted sequential
      studies to document genetic events leading to the development of malignant cells
      in vitro. We found that aneuploidy and extensive chromosome breaks and
      rearrangements occurred early. This is followed by inactivation of the
      retinoblastoma tumor-suppressor gene, amplification of the myc oncogene, and
      expression of the tumorigenic phenotype. Our observation of chromosome
      instability at the early phase of transformation is consistent with the mutator
      phenotype. We suggest that a cause of the instability is infidelity of DNA
      repair, and we have developed a challenge assay to elucidate this phenomenon. In
      this assay, cells are challenged to repair radiation-induced DNA lesions. In one
      of our studies, lymphocytes from cigarette smokers and nonsmokers were exposed to
      gamma rays in vitro. Cells from smokers had significantly more rearranged
      chromosomes than cells from nonsmokers after the challenge. These data suggest
      that smokers have infidelity of DNA repair and that this repair problem is a
      cause of health effects in smokers. In an in vitro study, lymphocytes were
      exposed to mitomycin C or to nickel acetate and then irradiated with gamma rays.
      Significantly increased frequencies of rearranged chromosomes were detected with
      low doses of mitomycin C and nickel, which do not cause chromosome damage by
      themselves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143637
TI  - Nitrated polycyclic aromatic hydrocarbons: a risk assessment for the urban
      citizen.
AB  - Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are formed during
      incomplete combustion. Sources include emissions from vehicles (mainly diesel
      vehicles), heating, smoking, certain types of food processing, and incomplete
      combustion in general. Nitro-PAHs are direct-acting mutagens, and a number of
      them have been shown to be carcinogens. 2-Nitrofluorene (NF) represents a model
      substance for the nitro-PAHs. An attempt has been made to calculate the human
      cancer risk due to exposure to nitro-PAHs by two different models. In the first
      model, genotoxic lesions were transferred to units of Gray (gamma-irradiation),
      and in the second model a mega study (24,000 animals) on the carcinogenicity of
      one metabolite of NF was used to elucidate the risk. Gamma-irradiation of the rat
      liver gave rise to preneoplastic foci in a dose-dependent manner, which was
      statistically significant. The Gray-equivalents of chemically (NF) induced foci
      were calculated, and from the human nitro-PAH exposure, expressed in Sievert, a
      human risk estimate was calculated. In the second model, an extrapolation from
      laboratory animals to man was performed because tumor data on 2
      acetylaminofluorene (AAF), a major metabolite of NF, were available in the
      literature. The tumor dose-response data on AAF was linear for tested lifetime
      doses. The results of both models agreed, with a risk range of 0.15-49 x 10(-6)
      on human cancer risk for an urban citizen.

PMID- 8143638
TI  - Development of bioassays and approaches for the risk assessment of 2,3,7,8
      tetrachlorodibenzo-p-dioxin and related compounds.
AB  - Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans
      (PCDFs), and related halogenated aromatic hydrocarbons (HAHs) are industrial
      compounds or by-products that have been identified as contaminants in almost
      every component of the global ecosystem. 2,3,7,8- Tetrachlorodibenzo-p-dioxin
      (TCDD) is the most toxic HAH, and studies in rodents have shown that this
      compound is a carcinogen. Analysis of environmental samples for HAHs has shown
      that these extracts contain complex mixtures of isomers and congeners, and this
      greatly complicates risk assessment due to the paucity of data available for most
      of the individual compounds. Extensive research has demonstrated a common
      receptor-mediated mechanism of action for TCDD and related toxic HAHs, and this
      has led to the development of a mechanism-based risk assessment approach for
      HAHs. Toxic equivalency factors (TEFs; relative potency compared to TCDD) have
      been developed for selected HAH congeners, and the TEF values can be used to
      determine "toxic equivalents" (TEQs) for HAH mixtures. In addition, several
      bioassays that use receptor-mediated end points have been developed and can be
      used directly to determine the TEQs for HAH mixtures. The applications of the
      TEF/TEQ approach for the risk assessment of HAHs are considerable, particularly
      with the conversion of complex analytical data into TEQs. However, there appear
      to be several limitations to this approach, particularly with PCBs because their
      potential nonadditive (antagonistic), interactive effects with "2,3,7,8-TCDD
      like" compounds may invalidate the use of the risk assessment procedure for some
      environmental matrices.

PMID- 8143639
TI  - Approaches to assessing genetic risks from exposure to chemicals.
AB  - An effort to assess and quantify genetic risks from human exposure to mutagenic
      chemicals is urgently needed; otherwise genetic toxicology may well lose its
      credibility. Genetic biomonitoring provides us with an indication of mutagenic
      effectiveness in human somatic cells. The populations and chemicals selected for
      such studies form a useful database for genetic risk-assessment studies.
      Extrapolation to what can be expected in germ cells of exposed individuals should
      be possible by using good dosimetry (adducts) and a parallelogram approach. The
      principle is that genetic damage in the inaccessible human germ cells can be
      estimated by determining the effects on lymphocytes (or other somatic cells) from
      humans and mice and in germ cells of mice. Worldwide, opportunities for the
      costly mouse germ cell studies are limited. Knowledge of type of DNA adducts,
      their persistence and/or removal and dominant lethal studies, will be helpful in
      predicting stage sensitivity. Extrapolation from a lowest effective dose level is
      proposed. The available data for ethylene oxide and benzene are reviewed. The
      risk of heritable translocations in progeny of populations exposed to ethylene
      oxide is so high that more precise estimates seem desirable. In discussing the
      expression of the induced mutations, the importance of dominant mutations and of
      heterozygous effects of deletions and other recessives is pointed out. The
      molecular changes underlying dominant mutations in man are more limited than is
      the case for recessive mutations. This raises the question whether mutagenic
      agents can produce the specific changes leading to recoverable, dominant
      mutations. Extrapolation from increased mutation rates to predictable increases
      of human disease, whether by doubling dose or direct methods, have been
      criticized.

PMID- 8143640
TI  - Evaluation of mutagenicity testing with Salmonella typhimurium TA102 in three
      different laboratories.
AB  - Thirty compounds of various chemical classes were investigated for mutagenicity
      in a collaborative study (three laboratories) using Salmonella typhimurium TA102.
      With five compounds, hydrazine sulfate, phenylhydrazine, hydralazine,
      glutardialdehyde, and glyoxal, mutagenicity was detected by all laboratories.
      Formaldehyde was assessed as weakly mutagenic in only one of three laboratories.
      The remaining 24 agents were uniformly described as non-genotoxic in TA102. In
      spite of the overall good qualitative agreement in the mutagenicity results
      between the three laboratories, some quantitative discrepancies occurred in the
      dose response of the mutagenic compounds. Varying inter- and intralaboratory
      differences in the spontaneous rate of revertants were obtained. The usefulness
      of the tester strain TA102 in routine mutagenicity testing is discussed.

PMID- 8143641
TI  - Genetic toxicology in developing countries: comments and recommendations.

PMID- 8143642
TI  - Peculiarities of carcinogenesis under simultaneous oral administration of
      benzo(a)pyrene and o-cresol in mice.
AB  - A modifying influence of ortho-cresol (o-cresol) on the carcinogenic effect of
      benzo(a)pyrene (BaP) with combined oral administration to CC57Br mice had been
      found. During simultaneous administration of o-cresol (1 mg) and BaP (1 mg), the
      incidence of tumors, the multiplicity of tumors, and the degree of malignancy all
      increased, but the latency was shortened. When o-cresol was administered before
      or after BaP (in identical doses), the carcinogenic effect was weakened. When o
      cresol (10 mg) and BaP (5 mg) were administered simultaneously, the incidence of
      malignant tumors was similar to controls receiving BaP only (13.8%), indicating
      inhibition of carcinogenesis.

PMID- 8143643
TI  - Quantitative and temporal relationships between DNA adduct formation in target
      and surrogate tissues: implications for biomonitoring.
AB  - DNA-carcinogen adducts offer a potential dosimeter for environmental
      genotoxicants reaching the exposed individual. Because the target tissues for
      many chemical carcinogens are not readily accessible for monitoring adducts in
      humans, peripheral blood lymphocytes (PBLs) have served as surrogate sources of
      exposed DNA. Both benzo[a]pyrene (BaP) and benzo[b]fluoranthene (BbF) are widely
      distributed in the environment as components of complex mixtures, such as
      automobile exhaust, cigarette smoke, foods, water, and urban air. Thus, human
      exposure to these chemicals is widespread, and they probably contribute to
      overall human lung cancer risk. The interpretation of the results of such studies
      would be enhanced by an understanding of the pharmacokinetics of specific DNA
      adduct formation and persistence in both target and surrogate tissues. Polycyclic
      aromatic hydrocarbons (PAHs) were administered to male Sprague-Dawley rats IP at
      100 mg PAH/kg body weight. Lung, liver, and PBL tissues were harvested 1, 3, 7,
      14, 28, and 56 days after treatment. DNA was extracted from each tissue and 32P
      postlabeling analysis of DNA adducts with nuclease P1 enhancement was conducted.
      In all three tissues, BaP-DNA adducts exhibit a similar pattern, reaching a
      maximum at 3-4 days, followed by a decrease to 56 days. For BbF, the maximum DNA
      adduct levels in each tissue were between 5 and 14 days after injection. By 56
      days after administration, the total adducts remaining in all tissues were
      measurable. Correlation analyses of the amount of DNA adducts in lung or liver
      compared to those found in the PBL of the same animals suggest a range of
      correlations (R2 = 0.67-0.83).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143644
TI  - Dip-strip method for monitoring environmental contamination of aflatoxin in food
      and feed: use of a portable aflatoxin detection kit.
AB  - Aflatoxin contamination of food and feed have gained global significance due to
      its deleterious effect on human and animal health and its importance in the
      international trade. The potential of aflatoxin as a carcinogen, mutagen,
      teratogen, and immunosuppressive agent is well documented. The problem of
      aflatoxin contamination of food and feed has led to the enactment of various
      legislation. However, meaningful strategies for implementation of this
      legislation is limited by nonavailability of simple, cost-effective method for
      screening and detection of aflatoxin under field conditions. Keeping in mind the
      analytical constraints in developing countries, a simple-to-operate, rapid,
      reliable, and cost-effective portable aflatoxin detection kit has been developed.
      The important components of the kit include a hand-held UV lamp (365 nm, 4 W
      output), a solvent blender (12,000 rpm) for toxin extraction, and adsorbent
      coated dip-strips (polyester film) for detecting and quantifying aflatoxin.
      Analysis of variance indicates that there were no significant differences between
      various batches of dip-strips (p > 0.05). The minimum detection limit for
      aflatoxin B1 was 10 ppb per spot. The kit may find wide application as a research
      tool in public health laboratories, environmental monitoring agencies, and in the
      poultry industry.

PMID- 8143645
TI  - European Community research on environmental mutagenesis and carcinogenesis.
AB  - Within the 12 Member States of the European Community (EC), environmental policy
      is now formulated primarily at Community level. As a result, the EC has important
      regulatory responsibilities for the protection of workers, consumers, and the
      general public from risks that may arise from environmental chemicals, foremost
      among them potential carcinogens and mutagens. An important part of EC
      environmental research and development is intended to provide a scientific basis
      for these regulations as well as increasing understanding of the basic mechanisms
      involved in environmental carcinogenesis and mutagenesis. This paper contains a
      brief introduction to EC environment policy and research, followed by an overview
      of EC chemicals control activities that are of particular relevance to the
      research and development program. Community-level research on environmental
      mutagenesis and carcinogenesis is then reviewed in some detail, including the
      achievements of recent projects, the scientific content of the current program,
      and perspectives for the future.

PMID- 8143646
TI  - Development of screening tests for aneuploidy induction by environmental
      pollutants.
AB  - When legally required mutagenicity testing of chemicals is undertaken, the
      important genetic end point of aneuploidy is not included because validated test
      methods are lacking. Therefore, the Commission of the European Communities (CEC)
      has funded a research program to develop and validate tests for aneuploidy
      induction. Ten chemicals, selected on the basis of their ability to interact with
      cell organelles relevant for aneuploidy induction, were tested in 11
      laboratories. The assays ranged from in vitro tubulin assembly studies to in vivo
      germ-cell tests. The results allow several conclusions: a) Fungal aneuploidy
      tests are not capable of detecting inhibitors of mammalian tubulin polymerization
      such as colchicine and vinblastine. Therefore, they will not play a role in
      screening for aneuploidy but are of value for studying the relationship between
      induced aneuploidy and recombination. b) Chemicals that induce aneuploidy in
      mammalian germ cells are readily detected in the in vitro mammalian cell systems.
      Some chemicals such as thiabendazole and thimerosal induce aneuploidy in vitro
      but do not appear to be very effective in vivo. c) Cell division aberrations
      induced in mammalian cells in vitro seem to be predictive for aneuploidy
      induction in the same cell type. Likewise, c-mitotic effects and cell cycle delay
      in vivo in mitotic and meiotic cells correlate with aneuploidy induction in the
      respective tissue. A second CEC Aneuploidy Program has started recently to refine
      the most promising test protocols, to provide understanding of variety of
      mechanisms by which chemicals induce aneuploidy, and to establish a data base for
      aneugens among environmental pollutants.

PMID- 8143647
TI  - Mutagenicity and human chromosomal effect of stevioside, a sweetener from Stevia
      rebaudiana Bertoni.
AB  - Leaves of Stevia rebaudiana Bertoni have been popularly used as a sweetener in
      foods and beverages for diabetics and obese people due to their potent sweetener
      stevioside. In this report, stevioside and steviol were tested for mutagenicity
      in Salmonella typhimurium strains TA98 and TA100 and for chromosomal effects on
      cultured human lymphocytes. Stevioside was not mutagenic at concentrations up to
      25 mg/plate, but showed direct mutagenicity to only TA98 at 50 mg/plate. However,
      steviol did not exhibit mutagenicity in either TA98 or TA100, with or without
      metabolic activation. No significant chromosomal effect of stevioside and steviol
      was observed in cultured blood lymphocytes from healthy donors (n = 5). This
      study indicates that stevioside and steviol are neither mutagenic nor clastogenic
      in vitro at the limited doses; however, in vivo genotoxic tests and long-term
      effects of stevioside and steviol are yet to be investigated.

PMID- 8143648
TI  - Computerized image analysis for determining micronucleus frequency.
AB  - A method for the computerized automation of micronucleus scoring is presented.
      The task is to identify the cultured, cytokinesis-blocked peripheral lymphocytes
      (CB cells) and their micronuclei (MN). The main parts of the hardware are the
      video camera attached to the microscope, the IBM-compatible personal computer
      with the video digitizer card, and the computer-controlled stage movement unit.
      The computerized image processing is based on determination and interpretation of
      contour lines of the CB cells, nuclei, and MN. The BNCTEST image processing
      software has been developed up to the demonstration phase, and now it has been
      prepared for the testing period of image series on a large scale.

PMID- 8143649
TI  - Hazard identification: efficiency of short-term tests in identifying germ cell
      mutagens and putative nongenotoxic carcinogens.
AB  - For more than a decade, mutagenicity tests have had a clearly defined role in the
      identification of potential human mutagens and an ancillary role in the
      identification of potential human carcinogens. The efficiency of short-term tests
      in identifying germ cell mutagens has been examined using a combined data set
      derived from the U.S. Environmental Protection Agency/International Agency for
      Research on Cancer Genetic Activity Profile (EPA/IARC GAP) and EPA Gene-Tox
      databases. Our review of these data indicates adequate sensitivity of batteries
      of in vitro short-term mutagenicity tests in identifying germ cell mutagens. The
      analysis also supports the inclusion of an in vivo assay as suggested in proposed
      regulatory testing guidelines. In the context of carcinogenicity testing, the
      ability of short-term bioassays to detect genotoxic or mutagenic carcinogens is
      well established. Such tests are not considered to be as sensitive to
      nongenotoxic or nonmutagenic carcinogens. However, analyses presented in this
      report using the EPA/IARC GAP database demonstrate that many putative
      nongenotoxic carcinogens that have been adequately tested in short-term genetic
      bioassays induce gene or chromosomal mutation or aneuploidy. Further
      investigation should reveal whether the mutagenicity of these agents plays an
      important mechanistic role in their carcinogenicity.

PMID- 8143650
TI  - Indications of repair of radon-induced chromosome damage in human lymphocytes: an
      adaptive response induced by low doses of X-rays.
AB  - Naturally occurring radon is a relatively ubiquitous environmental carcinogen to
      which large numbers of people can be exposed over their lifetimes. The
      accumulation of radon in homes, therefore, has led to a large program to
      determine the effects of the densely ionizing alpha particles that are produced
      when radon decays. In human lymphocytes, low doses of X-rays can decrease the
      number of chromatid deletions induced by subsequent high doses of clastogens.
      This has been attributed to the induction of a repair mechanism by the low-dose
      exposures. Historically, chromosome aberrations induced by radon have been
      considered to be relatively irreparable. The present experiments, however, show
      that if human peripheral blood lymphocytes are irradiated with low doses of X
      rays (2 cGy) at 48 hr of culture, before being exposed to radon at 72 hr of
      culture, the yield of chromatid deletions induced by radon is decreased by a
      factor of two. Furthermore, the numbers of aberrations per cell do not follow a
      Poisson distribution but are overdispersed, as might be expected because high
      linear energy transfer (high LET) alpha particles have a high relative biological
      effectiveness compared to low-LET radiations such as X-rays or gamma rays.
      Pretreatment with a low dose of X-rays decreases the overdispersion and leads to
      a greater proportion of the cells having no aberrations, or lower numbers of
      aberrations, than is the case in cells exposed to radon alone.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8143651
TI  - Enhancement of chromosomal damage by arsenic: implications for mechanism.
AB  - Arsenic is a naturally occurring metalloid that has been associated with
      increased incidence of human cancer in certain highly exposed populations.
      Arsenic is released to the environment by natural means such as solubilization
      from geologic formations into water supplies. It is also released to occupational
      and community environments by such activities as nonferrous ore smelting and
      combustion of fuels containing arsenic. Several lines of evidence indicate that
      arsenic acts indirectly with other agents to ultimately enhance specific
      genotoxic effects that may lead to carcinogenesis. Work described here indicates
      that arsenite specifically potentiates chromosomal aberrations induced by a DNA
      crosslinking agent, 1,3-butadiene diepoxide, but does not effect the induction of
      sister chromatid exchanges under the same treatment conditions. It is proposed
      that the specific co-clastogenic effects of arsenite seen here may be mediated by
      its interference with DNA repair activities. Further understanding of the
      mechanism by which arsenic interacts with other environmental agents will result
      in more accurate estimates of risk from exposure to arsenic.

PMID- 8143652
TI  - Variability in chromosome aberrations, sister chromatid exchanges, and mitogen
      induced blastogenesis in peripheral lymphocytes from control individuals.
AB  - Confidence in results from monitoring genetic end points in environmentally or
      occupationally exposed individuals can be improved with knowledge of the normal
      variability of changes in genetic end points in the general population.
      Confounding effects can be determined, and study interpretation can be improved
      by correlation of this variability with various lifestyle factors such as sex and
      age, smoking and drinking habits, viral infections, exposure to diagnostic X
      rays, etc. Eight blood samples were taken from each of 24 male and 24 female
      volunteers over a period of 2 years. Questionnaires pertaining to lifestyle were
      completed at the time of each sampling. Whole blood was cultured and slides
      prepared for chromosome aberration (CA) or sister chromatid exchange (SCE)
      analysis. Separated mononuclear cells were cultured with a range of
      phytohemagglutinin concentrations, and the maximum level of mitogen-induced
      blastogenesis was determined by measurement of [3H]thymidine uptake. There was a
      significant effect of both year and season of sampling for all three end points.
      Because there was no consistent pattern in 2 successive years, effects were
      thought to be independent of season. No significant effects in any of the three
      end points were found with respect to sex or age nor any of the other lifestyle
      factors, although SCE frequency and mitogen-induced blastogenesis were nearly
      always higher in females than in males. These results point to the need for
      concurrent sampling of controls with exposed populations.

PMID- 8143653
TI  - Monitoring human exposure to urban air pollutants.
AB  - A multidisciplinary study on a general population exposed to vehicle exhaust was
      undertaken in Pisa in 1991. Environmental factors such as air pollution and those
      associated with lifestyle were studied. Meanwhile, biological and medical
      indicators of health condition were investigated. Chromosomal aberrations, sister
      chromatid exchanges (SCEs), and micronuclei in lymphocytes were included for the
      assessment of the genotoxic risk. Because of the large number (3800) of subjects
      being investigated, standardization of protocols was compulsory. The results on
      data reproducibility are reported. To assess the reliability of the protocol on a
      large scale, the population of Porto Tolle, a village located in northeast Italy,
      was studied and compared to a subset of the Pisa population. Preliminary results
      showed that probable differences between the two populations and individuals were
      present in terms of SCE frequencies. The study was potentially able to detect the
      effects of several factors such as age, smoking, genetics, and environment. The
      in vitro treatment of lymphocytes with diepoxybutane confirmed the presence of
      more responsive individuals and permitted us to investigate the genetic
      predisposition to genetic damage. The possible influence of environmental factors
      was studied by correlation analyses with external exposure to air pollutants as
      well as with several lifestyle factors.

PMID- 8143654
TI  - Sensitivity of lymphocytes from vulcanizers to the in vitro induction of sister
      chromatid exchanges.
AB  - Spontaneous frequencies of sister chromatid exchanges (SCEs) and SCEs induced in
      vitro by chemicals with different mechanisms of action such as mitomycin C, 4
      nitroquinoline oxide, and 3-aminobenzamide were examined in phytohemagglutinin
      stimulated peripheral blood lymphocytes from a group of workers in a rubber plant
      and a control group, both of which had been analyzed for levels of spontaneous
      SCEs 2 years earlier. An interindividual variability in the induction of SCEs was
      found after in vitro treatments with the different mutagens, which did not
      correlate with occupational exposure. This variability in the sensitivity to the
      induction of SCEs might be correlated to genetic differences among individuals,
      which have to be taken into account in environmental monitoring programs.

PMID- 8143655
TI  - Rhodococcus equi vertebral osteomyelitis in foals.

PMID- 8143656
TI  - Epidemiology of equine Cryptosporidium and Giardia infections.
AB  - Prevalence and infection patterns of Cryptosporidium and Giardia infections in
      horses were studied by a direct immunofluorescence staining method. Faecal
      examinations of 222 horses of different age groups revealed Cryptosporidium
      infection rates of 15-31% in 66 foals surveyed in central Ohio, southern Ohio and
      central Kentucky, USA. Only 1 of 39 weanlings, 0 of 46 yearlings, and 0 of 71
      mares were positive. Giardia infection was found in all age groups, although the
      infection rates for foals were higher (17-35%). Chronological study of infection
      in 35 foals showed that foals started to excrete Cryptosporidium oocysts between
      4 and 19 weeks and Giardia cysts between 2 and 22 weeks of age. The cumulative
      infection rates of Cryptosporidium and Giardia in foals were each 71%. Some foals
      were concurrently infected with both parasites and excretion of oocysts or cysts
      was intermittent and long-lasting. The longest duration of excretion was 14 weeks
      for Cryptosporidium and 16 weeks for Giardia. Excretion of Cryptosporidium
      oocysts stopped before weaning, while excretion of Giardia cysts continued
      thereafter. Infected foals were considered the major source of Cryptosporidium
      infection in foals, whereas infected mares were deemed the major source of
      Giardia infection in foals. The high infection rate of Giardia in nursing mares
      suggested a periparturient relaxation of immunity. The results indicated that
      Cryptosporidium and Giardia infections are common in horses.

PMID- 8143657
TI  - An analysis of 75 cases of intestinal obstruction caused by pedunculated lipomas.
AB  - A retrospective study of 75 cases of pedunculated lipoma obstruction (PLO) of the
      intestine was conducted. Age, breed and sex distributions were compared to the
      non-PLO colic population. Horses in the PLO group were significantly older than
      in the non-PLO colic group (P < 0.001). A significant increase in risk of PLO was
      associated with geldings (O.R. 2.32) and with ponies (O.R. 3.75). Of the 75 PLO
      cases analysed, 69 were strangulating, 70 involved small intestine and 5 involved
      small colon. Cases of strangulation obstruction tended to have lipomas
      originating distant to the mesenteric border of the intestine. The short-term
      survival rate for PLO cases was 48%. Long-term survival rate was 38%. Lipoma
      weight of some of the PLO group was compared with that from an asymptomatic
      pedunculated lipoma (APL) group. The two weight distributions were significantly
      different (P < 0.001).

PMID- 8143658
TI  - Susceptibility of ponies to infection with Streptococcus pneumoniae (capsular
      type 3)
AB  - Welsh Mountain ponies were inoculated with an isolate of Streptococcus
      pneumoniae, SPE 1618 (capsular type 3) recovered from the equine respiratory
      tract: 10 ml of a suspension of 10(8) or 10(9) cfu/ml were instilled
      intratracheally. Fever was observed after either dose but the greater
      concentration also produced coughing, ocular and nasal discharge, depression and
      enlargement of submandibular lymph nodes. Cytological evidence of infection was
      also observed in tracheal washings during the first week after inoculation and
      corresponded with isolation of S. pneumoniae from the washes. Morbid anatomical
      and histopathological examinations of selected animals revealed focal pneumonia
      affecting the ventral lung, especially the cardiac area and accessory lobe, with
      a propensity to affect the right lung. S. pneumoniae was isolated directly in
      pure culture from these lesions or was demonstrable by immunostaining of
      macrophages bearing specific capsular type 3 antigen. By 10 days after
      inoculation, the ponies were healthy and had developed antibodies to S.
      pneumoniae. S. pneumoniae was therefore a primary pathogen in the horse under the
      conditions of the challenge.

PMID- 8143659
TI  - Quantitative analysis of cyanogen bromide-cleaved peptides for the assessment of
      type I: type II collagen ratios in equine articular repair tissue.
AB  - Cyanogen bromide was used to solubilise and specifically fragment purified equine
      Type I and II collagen and equine articular surface repair tissue. The resultant
      peptides were separated by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis and quantified by densitometric scanning. Measurement of the
      relative amounts of the peptides alpha 2(I) CB3, 5 and alpha 1(II)CB10 provided
      an accurate method of establishing the ratio of Type I to Type II collagen in
      mixtures of purified equine collagens. The method was sensitive to 6% Type II
      collagen when the band areas were corrected for peptide molecular weight and the
      number of chains in the parent tropocollagen molecule which contain that
      particular peptide. Use of this technique showed that repair tissue in full
      thickness osteochondral defects in the dorso-distal margins of the intermediate
      carpal bones of ponies did not contain detectable amounts of Type II collagen 11
      weeks after defect induction.

PMID- 8143660
TI  - Effect of central or marginal location and post-operative exercise on the healing
      of osteochondral defects in the equine carpus.
AB  - The effects of osteochondral defect location and post-operative walking exercise
      on structural repair and recovery of joint function were examined in the
      midcarpal joints of ponies. Functional recovery was monitored by measuring ground
      reaction forces using a force plate. Structural repair was evaluated
      histologically and by measuring the total collagen and uronic acid content and
      relative proportions of Type I and II collagen in the repair tissue. Central
      defects tended to cause a more marked functional disturbance but were repaired
      with fibrocartilage rather than fibrous tissue in 3 out of 6 ponies while
      marginal defects were repaired almost exclusively with fibrous tissue. There was
      no significant difference between defect locations with regard to the biochemical
      measures evaluated. Exercise produced no beneficial effect on structural repair
      of the defects. Secondary 'kissing' lesions in the third carpal bones opposite
      the defects appeared grossly more severe in the exercised ponies which also
      showed a trend to more marked functional disturbance.

PMID- 8143661
TI  - Parasitic protozoa of horses: a subject of burgeoning concern.

PMID- 8143662
TI  - Influence of intra-articular sodium hyaluronate and polysulphated
      glycosaminoglycans on the biochemical composition of equine articular surface
      repair tissue.
AB  - The influence of repeated intra-articular injections of sodium hyaluronate and
      polysulphated glycosaminoglycan on the repair of full-thickness osteochondral
      defects was examined in the midcarpal joints of ponies. The study showed no
      significant difference between treated and control groups with regard to total
      collagen content, uronic acid content or the relative proportions of Type I and
      Type II collagen in the repair tissue, indicating that the drugs did not affect
      the biochemical composition of the repair tissue 11 weeks after defect induction.

PMID- 8143663
TI  - Cellular sources of proteolytic enzymes in equine joints.
AB  - Isolated equine blood and articular cells were investigated for proteolytic
      enzyme production by means of gel filtration and analysis on 14C-acetylated
      collagen and casein substrates. Significant amounts of collagenase and caseinase
      activity were produced by cultured synoviocytes stimulated with equine
      interleukin 1, although large amounts of collagenase also originated from
      neutrophils.

PMID- 8143664
TI  - Proteolytic enzymes in equine joints with infectious arthritis.
AB  - Significant amounts of collagenase and caseinase activity were detected in
      infected synovial fluid samples. Partial characterisation of the enzymes by gel
      filtration suggested that synovial fluid from cases of infectious arthritis may
      contain enzymes from both the synovial cells and neutrophils. This finding was
      also supported by analysis of sequential synovial fluid samples from 4 infected
      joints. In 3 joints the concentration of caseinase and in 1 joint collagenase
      paralleled the decline in total nucleated cell count. However, in 3 joints the
      concentration of collagenase remained high after the total nucleated cell count
      had returned to normal, suggesting that this enzyme originated from resident
      articular cells.

PMID- 8143665
TI  - Streptococcus pneumoniae and equine disease.

PMID- 8143666
TI  - Frusemide attenuates the exercise-induced rise in pulmonary capillary blood
      pressure in horses.
AB  - Catheter mounted micro-tip-manometers (the signals from which were matched with
      fluid-filled pressure signals from same cardiovascular sites and zeroed at the
      point of the shoulder), were used to study pulmonary haemodynamics in 8 healthy
      sound horses at rest and during exercise performed at 8, 10, 12 and 14 m/s on a
      treadmill. Measurements were made without frusemide (control) and 4 h after iv
      administration of 250 mg frusemide. Post-frusemide data were also obtained on a
      separate day, and these observations were not significantly different from those
      made on the same day as controls. Pre-frusemide values of heart rate, mean right
      atrial pressure, mean pulmonary artery pressure, mean pulmonary artery wedge
      pressure and mean pulmonary capillary pressure at 14 m/s were 214 +/- 5
      beats/min, 54 +/- 4, 92 +/- 4, 65 +/- 6 and 79 +/- 5 mmHg, respectively. Exercise
      at 14 m/s after frusemide resulted in a similar heart rate (216 +/- 4 beats/min),
      but the mean right atrial, pulmonary arterial, pulmonary artery wedge and
      pulmonary capillary pressures were all significantly lower, i.e. 34 +/- 5, 79 +/-
      4, 45 +/- 4, and 62 +/- 3 mmHg, respectively. Attenuation, by frusemide, of the
      exercise-induced rise in pulmonary capillary pressure would lower the magnitude
      of the transmural force exerted on the pulmonary capillaries. If, therefore,
      exercise-induced pulmonary haemorrhage (EIPH) is caused by stress failure of
      pulmonary capillaries, frusemide pretreatment has the potential for
      reducing/limiting the extent of EIPH.

PMID- 8143667
TI  - Measurements of urethral pressure profiles in the male horse.
AB  - Urinary tract pressure profiles were evaluated in 6 clinically normal geldings
      over 3 consecutive days. This was performed by introducing a 1.3 m-long cuffed
      catheter into the urinary tract, under xylazine sedation (0.8 mg/kg, iv). The
      method was reproducible. The mean (+/- sd) intra-vesicular pressure (IVP) and
      maximal urethral closure pressures (MUCP) were 10.3 (+/- 1.7) and 129.8 (+/-
      19.6) cmH2O, respectively, and the ratio between MUCP and IVP was 13.2 (+/- 2.5).
      A gelding with urinary incontinence showed a significantly lower MUCP (73.4
      cmH2O), and an MUCP to IVP ratio of 8.0. It was concluded that the day-to-day
      variation was non-significant, and that the technique may be useful in the
      differential diagnosis of urinary incontinence in male horses.

PMID- 8143668
TI  - Ultrasonographic assessment of the proximal digital annular ligament in the
      equine forelimb.
AB  - Ultrasonography was used with 6 normal cadaver forelimbs of Dutch Warmblood
      horses to delineate the ultrasonographic anatomy of the palmar pastern region,
      with emphasis on the proximal digital annular ligament. Using a 5.5 MHz sector
      scanner, the thin proximal digital annular ligament was not visible on offset
      sonograms. Only if the digital sheath in the normal limb was distended was the
      distal border of this ligament outlined. In all normal limbs the palmarodistal
      thickness of the combined skin-proximal digital annular ligament layer in the mid
      pastern region was 2 mm. The flexor tendons and distal sesamoidean ligaments were
      easily identified as hyperechoic structures. Distension of the digital sheath in
      the normal limbs clearly outlined the anechoic digital sheath pouches. In 4 lame
      horses ultrasonography aided the diagnosis of functional proximal digital annular
      ligament constriction. In all 4 diseased forelimbs ultrasonography demonstrated
      thickening of the skin-proximal digital annular ligament layer and distension of
      the digital sheath. In one of these limbs the distended digital sheath was also
      thickened. The flexor tendons and distal sesamoidean ligaments were normal. There
      was no radiographic evidence of additional bone or joint lesions.

PMID- 8143669
TI  - Evaluation of myeloperoxidase concentrations in experimentally induced equine
      colonic ischaemia and reperfusion.

PMID- 8143670
TI  - Indirect Doppler ultrasonic measurement of arterial blood pressure results in a
      large measurement error in dorsally recumbent anaesthetised horses.

PMID- 8143671
TI  - Rhodococcus equi vertebral osteomyelitis in 3 quarter horse colts.

PMID- 8143672
TI  - Vertebral body osteomyelitis due to Rhodococcus equi in two Arabian foals.

PMID- 8143673
TI  - Myelodysplastic syndrome in a quarter horse gelding.

PMID- 8143674
TI  - Review of equine Cryptosporidium infection.

PMID- 8143675
TI  - The determination of cocaine and related substances by micellar electrokinetic
      capillary chromatography.
AB  - A quantitative method for the determination of cocaine and related substances by
      micellar electrokinetic capillary chromatography (MECC) is described.
      Quantitative results obtained for both monitor materials and a number of actual
      drug seizures by this new capillary electrophoretic method are comparable to a
      gas chromatography (GC) run in parallel, both in the values and coefficient of
      variation achieved. The advantages of this new method include minimal use of
      solvents, the ability to readily automate the procedure and the ability to
      quantitate illicit heroin seizures under the same conditions with the exception
      of detector wavelength alteration. The method has proved rugged and reliable for
      both heroin and cocaine in a number of inter-laboratory proficiency studies.

PMID- 8143676
TI  - Characterization of proteins by capillary electrophoresis in fused-silica
      columns: review on serum protein analysis and application to immunoassays.
AB  - Protein mixtures can be characterized in terms of their separations by capillary
      electrophoresis (CE). The separation of proteins by CE is performed in untreated
      fused-silica columns. Model proteins and complex protein mixtures with pI values
      ranging from 4.0 to 11.0 are separated in such columns in less than 10 min in the
      presence of phosphate buffer with a pH between 4.0 and 9.0. The application of CE
      separation procedures for routine analysis of protein in serum, urine, and
      cerebrospinal fluid in borate-based buffer is also demonstrated. The detection of
      protein in CE is usually based on the intrinsic ultraviolet (UV) absorbance of
      the peptide bond at or near 200 nm, which provides a detection limit of about 10(
      5) M. The same protein separation procedures can also be applied to
      immunochemical reaction systems in which one component is labeled. Thus, an
      antigen analyte, or the antibody to the analyte, may be labeled with a fluor and
      detected by laser-induced fluorescence (LIF). With a fluorescent-labeled
      reactant, the use of LIF detection further extends the detection limit to 10(-11)
      M. The CE separation technique for proteins provides a means to separate the
      bound and free species of the labeled antigen or antibody without the use of a
      solid support. The application of these separation techniques in conjunction with
      laser-induced fluorescence detection to make possible the homogeneous
      immunochemical measurement of species at concentrations in the range of 10(-9) to
      10(-10) M is shown.

PMID- 8143677
TI  - Clinical and forensic applications of capillary electrophoresis.
AB  - This survey is aimed at giving the readers a short overview of the present state
      of the art of clinical and forensic applications of capillary electrophoresis.
      First, the principles associated with electrokinetic capillary separations and
      instrumentation, sample preparation and solute quantitation are briefly
      discussed. This is followed by chapters describing the determination of
      endogenous and exogenous compounds in body fluids and tissue extracts. Finally, a
      survey of major achievements including reference to fully developed
      electrokinetic capillary assays is provided. The paper concludes with a brief
      outlook.

PMID- 8143678
TI  - Analysis of lipoproteins with analytical capillary isotachophoresis.
AB  - An analytical free flow capillary isotachophoresis procedure, with a
      discontinuous electrolyte system, for the detailed analysis of lipoproteins in
      human body fluids has been developed. The technique is based on prestaining whole
      serum lipoproteins with a lipophilic dye before separation. Human serum
      lipoproteins are separated into 14 well-characterized subfractions according to
      their electrophoretic mobility. High density lipoproteins (fraction 1 to 6) are
      separated into three major subpopulations, the fast migrating high density
      lipoprotein (HDL) subpopulation, containing mainly apo AI and
      phosphatidylcholine, the subpopulation with intermediate mobility, consisting of
      particles rich in apo AII, apo E, and C apolipoproteins, and the slowly migrating
      HDL subfraction, containing mainly particles rich in apo AI, apo AIV, and
      lecithin: cholesterol acyltransferase (LCAT) activity. The apo B containing
      lipoproteins (fraction 7 to 14) can be subdivided into four major functional
      groups. The first represents chylomicron derived particles and large triglyceride
      rich very low density lipoproteins (VLDL). The second group consists of small
      VLDL and intermediate density lipoprotein (IDL) particles, anf the third and
      fourth group represent the low density lipoproteins. The isotachophoretic
      analysis of human serum samples obtained from patients with hyperlipoproteinemias
      is compatible with the classification according to the Frederickson phenotypes
      and reflects the respective biochemical abnormalities. Furthermore, several
      genetic disorders of lipid and lipoprotein metabolism like HDL deficiency
      syndromes, familial LCAT deficiency, Fish eye disease, hypobetalipoproteinemia
      and abetalipoproteinemia can be well characterized by analytical capillary
      isotachophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143679
TI  - Determination of 2-5A synthetase and 2-5A phosphodiesterase in neuroblastoma
      cells by analytical capillary isotachophoresis: effects of cytokines and
      comparison with radioenzymatic methods.
AB  - 2-5A Synthetase and 2-5A phosphodiesterase were determined by analytical
      capillary isotachophoresis in comparison to radioenzymatic methods. By means of
      isotachophoretic analysis, a frequently used radioenzymatic 2-5A synthetase assay
      was optimized and the results of both assays were compared. Using the
      isotachophoretic assay the influence of interferon-related cytokines (tumor
      necrosis factor-alpha and interleukin-2) on 2-5A synthetase induction in
      neuroblastoma cells was estimated. In contrast to mononuclear blood cells, the
      tumor necrosis factor induced 2-5A synthetase in these cells. 2-5A
      Phosphodiesterase was determined using an isotachophoretic assay and a
      radioenzymatic method. Degradation of A2'p5'A2'p5'A (trimeric form of 2-5A core)
      was measured by isotachophoresis whereas degradation of a mixture of phosphorus
      32 labeled 2-5A cores was registered by radioenzymatic assay. Activity of 2-5A
      phosphodiesterase was only insignificantly enhanced by interferon in mononuclear
      blood and neuroblastoma cells. In contrast to the radioenzymatic assays, an
      accurate determination of 2-5A synthetase as well as of 2-5A phosphodiesterase is
      possible using the isotachophoretic method because the reactions are followed by
      measuring the substrates ATP and A2'p5'A2'p5'A, respectively.

PMID- 8143680
TI  - Detection of neurotensin in tissues by capillary zone electrophoresis.
AB  - An electrophoretic method for detecting neurotensin in tissues was developed.
      Homogenates of rat duodenum and adrenal glands were first extracted by solid
      phase extraction and purified by reversed-phase high-performance liquid
      chromatography. The neurotensin-rich fraction was further analyzed by capillary
      zone electrophoresis (CZE) using a commercial instrument with UV detection. A
      minor peak was detected as neurotensin and its identity was further confirmed by
      performing several CZE analyses at different pH values. Such an approach could be
      used to analyze with good molecular specificity the neuropeptides in some human
      tissues.

PMID- 8143681
TI  - Factors affecting the determination of drugs and endogenous low molecular mass
      compounds in human serum by micellar electrokinetic capillary chromatography with
      direct sample injection.
AB  - Factors influencing the establishment of an analytical window in front of the
      solubilized proteins in micellar electrokinetic capillary chromatography (MECC)
      with direct serum injection (DSI) are discussed. Both drugs and endogenous low
      molecular mass compounds eluting within the analytical window are identified
      concurrently by multi-wavelength absorption detection. Variables such as the
      concentration of the micelle forming substance, ionic strength, applied voltage,
      initial sample zone length, capillary length, selected buffer additives,
      insufficient renewal of the buffer in the anodic buffer vial and sample matrix
      are shown to impact MECC of endogenous compounds and model drugs, such as
      antiepileptics. For two drugs eluting within the analytical window, phenobarbital
      and ethosuximide, serum levels determined by DSI with external calibration are
      shown to compare well with levels obtained after liquid-liquid extraction and
      internal calibration (use of an internal standard). In addition, reproducibility
      of both assays is excellent. The limit of employing DSI is demonstrated with the
      determination of the hydrophobic drug phenytoin. Using an automated, commercial
      instrument and naproxen as model drug, high-speed MECC separations of high
      reproducibility and with a throughput of 12-15 samples per h are presented.

PMID- 8143682
TI  - Investigation of drug metabolism using capillary electrophoresis with photodiode
      array detection and online mass spectrometry equipped with an array detector.
AB  - The application of capillary electrophoresis (CE) with photodiode array detection
      (DAD) and on-line CE-mass spectrometry (CE-MS) equipped with a position and time
      resolved (PATRIC) focal plane detector for analysis of both in vitro and in vivo
      drug metabolism is demonstrated. Separation of metabolites derived from the
      neuroleptic drug haloperidol, by CE, using a simple, volatile run buffer
      containing 50 mM ammonium acetate with 10% methanol and 1% acetic acid is
      reported. The potential utility of CE-DAD for screening drug metabolite mixtures
      derived from hepatic microsomal incubations is demonstrated for haloperidol
      (HAL). Also the potential problems associated with using this technology to
      screen human urine samples for HAL metabolites is discussed. Furthermore, the
      usefulness of CE-MS and CE-electrospray ionization skimmer collision induced
      dissociation-MS (CE-ESI-CID-MS) in identification and structure elucidation of
      HAL metabolites derived from both a guinea pig hepatic microsomal incubation and
      urine from a patient treated with 0.5 mg/day of HAL is shown. The utility of such
      an approach in the general area of clinical pharmacology is also discussed.

PMID- 8143683
TI  - Micellar electrokinetic capillary chromatography of benzodiazepines in human
      urine.
AB  - The determination of the major urinary compounds of eight common benzodiazepines,
      flunitrazepam, diazepam, midazolam, clonazepam, bromazepam, temazepam, oxazepam,
      and lorazepam, by micellar electrokinetic capillary chromatography (MECC) is
      shown to be a simple and attractive approach for confirmation testing of these
      drugs in human urine. After enzymatic hydrolysis and extraction using mixed-mode
      solid-phase cartridges and a two-step elution protocol, fractions were analyzed
      in a phosphate/borate buffer (pH 9.3) containing 75 mM sodium dodecyl sulfate and
      small amounts of isopropanol, methanol and/or acetonitrile using an instrument
      with on- column multi-wavelength detection. The presence of these compounds could
      unambiguously be confirmed in patient urines which tested positive for
      benzodiazepines using a commercial enzyme multiplied immunoassay screening
      technique (EMIT). The sensitivity of the MECC assay is demonstrated to be better
      than that of EMIT. MECC analysis of one patient urine which tested negatively
      employing EMIT revealed the presence of lorazepam, this demonstrating that false
      negative results from the initial immunological screening process can be
      recognized using MECC. For one example, 7-aminoflunitrazepam, the MECC data are
      shown to agree well with those obtained by gas chromatography/mass spectrometry.

PMID- 8143684
TI  - Pharmaceutical and biomedical applications of capillary
      electrophoresis/electrochemistry.
AB  - The use of capillary electrophoresis/electrochemistry (CEEC) for the analysis of
      microdialysis samples obtained for pharmacokinetic and neurochemical studies is
      described, as well as the development of new types of electrodes and waveforms
      which increase the selectivity of this technique for specific classes of
      analytes. CEEC with a carbon fiber electrode was employed for the analysis of
      microdialysis samples. Microdialysis is an in vivo sampling technique that yields
      very small samples for analysis (less than 1 microL). Therefore, capillary
      electrophoresis, with its small volume requirements, is an excellent choice for
      the analytical method. CEEC was used to study the pharmacokinetics of L-dopa and
      the release of aspartate and glutamate following a high K+ infusion in the brain.
      Several modified electrodes which increase the applicability of CEEC in
      pharmaceutical and biomedical analysis are described. One of these is a
      gold/mercury electrode which is highly selective for thiols and was used for the
      determination of glutathione in a rat brain. An alternative method for the
      detection of thiols employed a chemically modified electrode containing cobalt
      phthalocyanine. In this case, an electrocatalyst reduces the overpotential of
      thiols at the carbon electrode and makes it possible to detect them at a much
      lower and more selective oxidation potential. This electrode was used for the
      detection of cysteine in urine. The development of pulsed amperometric detection
      for capillary electrophoresis is also described and is demonstrated by the
      detection of glucose in blood. Lastly, a method for the detection of peptides
      based on the formation of a copper complex and detection at a carbon fiber
      electrode is discussed.

PMID- 8143685
TI  - Analysis of mephenytoin, 4-hydroxymephenytoin and 4-hydroxyphenytoin enantiomers
      in human urine by cyclodextrin micellar electrokinetic capillary chromatography:
      simple determination of a hydroxylation polymorphism in man.
AB  - Using cyclodextrin micellar electrokinetic capillary chromatography (CD-MECC),
      baseline separation of mephenytoin, 4-hydroxymephenytoin and 4-hydroxyphenytoin
      enantiomers in urine was effected with beta-cyclodextrin. After single-dose
      administration of 100 mg of racemic mephenytoin, the 0-8 h urine was collected,
      and enzymatically hydrolyzed urine specimens were applied. For extensive
      metabolizers, a single peak for 4-hydroxymephenytoin was detected corresponding
      to the S-enantiomer. This peak was either very small or undetectable in samples
      of poor metabolizers. Typically, mephenytoin could not be detected in these
      samples. However, application of undeglucuronidated extracts revealed the
      presence of free S-4-hydroxymephenytoin and R,S-mephenytoin and thus permitted
      phenotyping via both the urinary S:R enantiomeric ratio of mephenytoin and the
      hydroxylated metabolite. Application of enzymatically hydrolyzed and extracted
      urines after phenytoin administration (100 mg; 0-8 h urine collection) revealed
      the presence of S-4-hydroxyphenytoin. Thus, CD- MECC is shown to be a simple and
      attractive approach for (i) the confirmation of the stereoselectivity of the
      aromatic hydroxylation of mephenytoin and phenytoin, (ii) the simple and rapid
      differentiation between extensive and poor metabolizers for mephenytoin, and
      (iii) assessment of compliance.

PMID- 8143686
TI  - Capillary zone electrophoresis determination of phenylalanine in serum: a rapid,
      inexpensive and simple method for the diagnosis of phenylketonuria.
AB  - A simple, rapid, and quantitative capillary zone electrophoresis method for
      phenylalanine analysis in serum has been developed, with the aim of providing an
      analytical tool, as an alternative to liquid and gas chromatography, for the
      routine laboratory diagnosis of phenylketonuria. Electrophoresis was carried out
      in a 65 cm long, 50 microns wide bare silica capillary, using 0.025 M borate
      (adjusted to pH 10 with 1 M NaOH) at a potential of 20 kV, with in-column UV
      detection at 214 nm. Under these conditions, the three aromatic amino acids
      (tryptophan, phenylalanine and tyrosine) migrated according to the pKs of the
      respective amine (and hydroxyl) groups. The efficiency of separation was about
      150,000 plates/column for phenylalanine. Diprophylline was adopted as internal
      standard. The injection of ethanol-deproteinized normal control serum gave rise
      to only a few major peaks not interfering with phenylalanine; phenylalanine in
      serum at normal concentrations appeared in a clean region of the electropherogram
      as a symmetrical peak with a migration time of about 11 min. The sensitivity was
      > or = 3 micrograms/mL, with s/n ratio = 3. The linearity, in the range of 5-175
      micrograms/mL, was described by the equation y = 1.407-0.583 x, r2 = 0.9998.
      Accuracy and precision were satisfactory, with intra-day and inter-day
      coefficients of variation lower than 4% and 7%, respectively. The injection of
      sera from five phenylketonuria patients gave electropherograms clearly showing
      huge peaks of phenylalanine, thus allowing an easy laboratory diagnosis of
      phenylketonuria.

PMID- 8143687
TI  - Application of micellar electrokinetic capillary chromatography for monitoring of
      hippuric and methylhippuric acid in human urine.
AB  - The factors affecting micellar electrokinetic capillary chromatographic
      separation of hippuric and o-, m-, p-methylhippuric acid were investigated by
      changing the species of micelles, and adding urea to the micellar solution. The
      analysis of hippurates in human urine is demonstrated under optimum conditions
      using 20 mM phosphate buffer (pH 8.0) containing 100 mM dodecyltrimethylammonium
      bromide and 4 M urea at -22 kV applied voltage. This method proved suitable for
      the screening of hippurates in human urine following occupational exposure to
      toluene and xylene.

PMID- 8143688
TI  - Evaluation of serum lactate dehydrogenase activity for estimation of energy
      expenditure in human subjects.
AB  - We investigated the relationship between serum lactate dehydrogenase (LDH)
      activity and energy expenditure in young adults, evaluating their serum LDH
      activities in order to develop an index of energy expenditure. The results
      obtained were as follows. (1) There were significant correlations between the
      serum LDH activity and energy expenditure/day, energy expenditure/body weight/day
      and daily activity index in men. (2) There were significant correlations between
      the serum LDH activity and energy expenditure/day and daily activity index in
      women. (3) A group of men who 'rarely' exercised had lower levels of serum LDH
      activity than those who exercised 'sometimes' or 'usually', but little difference
      was noted between similar groups of women.

PMID- 8143689
TI  - Using computer-based models for predicting human thermal responses to hot and
      cold environments.
AB  - Four influential models, capable of predicting human responses to hot and cold
      environments and potentially suitable for use in practical applications, were
      evaluated by comparing their predictions with human data published previously.
      The models were versions of the Pierce Lab 2-node and Stolwijk and Hardy 25-node
      models of human thermoregulation, the Givoni and Goldman model of rectal
      temperature response, and ISO/DIS 7933. Experimental data were available for a
      wide range of environmental conditions, with air temperatures ranging from -10 to
      50 degrees C, and with different levels of air movement, humidity, clothing and
      work. The experimental data were grouped into environment categories to allow
      examination of the effects of variables, such as wind or clothing, on the
      accuracy of the models' predictions. This categorization also enables advice to
      be given regarding which model is likely to provide the most accurate predictions
      for a particular combination of environmental conditions. Usually at least one of
      the models was able to give predictions with an accuracy comparable with the
      degree of variation that occurred within the data from the human subjects. The
      evaluation suggests that it is possible to make useful predictions of deep-body
      and mean skin temperature responses to cool, neutral, warm and hot environmental
      conditions. The models' predictions of deep-body temperature in the cold were
      poor. Overall, the 25-node model provided the most consistently accurate
      predictions. The 2-node model was often accurate but could be poor for exercise
      conditions. The rectal-temperature model usually overestimated deep-body
      temperature, although its predictions for very hot or heavy exercise conditions
      could be useful. The ISO model's allowable exposure times would not have
      protected subjects for some exercise conditions.

PMID- 8143690
TI  - Assessment of the relative effects of alcohol on different types of job
      behaviour.
AB  - A study was conducted to determine the effects of alcohol ingestion on
      performance on the four behavioural processes that constitute most industrial
      tasks; perception, mediation, communication, and motor control. In this research,
      a single task that incorporated all four of the behavioural processes was
      designed, so that the relative effects of alcohol on the processes could be
      studied. Regression equations were developed which provide a model for the
      assessment of the impact of alcohol ingestion on industrial task performance.

PMID- 8143691
TI  - Carpal tunnel syndrome: a products liability prospective.

PMID- 8143692
TI  - Electromyographic activity during typewriter and keyboard use.
AB  - This study investigated how ergonomic design influences neck-and-shoulder muscle
      strain, through keyboard assessment. Muscular activity was measured
      electromyographically (EMG) from six muscles in the forearm and shoulders of
      eight experienced typists using each of five different types of keyboard: one
      mechanical, one electromechanical, and one electronic typewriter; one personal
      computer/word processor (PC-XT) keyboard; and one angled at 20 degrees in the
      horizontal plane. The impact on muscular activity of using a palmrest was also
      studied. The mechanical typewriter induced a higher strain in the forearm and
      finger muscles than did the modern typewriters and keyboards. These induced no
      different strain on the neck-and-shoulder muscles, except for the right shoulder
      muscle, which was more active with the electronic typewriter than with the other
      machines. Using a palmrest did not decrease the strain on the muscles
      investigated. Use of the 'angled' PC-XT keyboard did not influence the measured
      muscular load on the forearm and finger muscles compared to typing on an ordinary
      PC-XT keyboard, but decreased the extensor muscular strain compared to the
      electronic typewriter.

PMID- 8143693
TI  - A rapid appraisal of occupational workload from a modified scale of perceived
      exertion.
AB  - A simple and rapid method of determining occupational workload among Indian women
      performing manual activities was developed based on the strong relationship
      between physiological responses and subjective feeling of exertion. A modified
      five point scale of perceived exertion, sequentially numbered 1 to 5, was created
      to simplify the complicated and time-consuming procedures using conventional
      methods of measuring energy expenditure, or even heart rate responses, during
      work of very short duration, especially in field situations. The scale denotes
      physiological workload: 1: very light; 2: light; 3: moderately heavy; 4: heavy;
      and 5: very heavy. A job-classification table based on energy expenditure and
      heart rate responses is also proposed, and different household activities such as
      grinding masalas, dish washing, sweeping, mopping, ironing, storing water, etc.
      have been graded accordingly.

PMID- 8143694
TI  - The three-dimensional measurement of unconstrained motion using a model-matching
      method.
AB  - The measurement of motion is a basic technique for the quantitative mechanical
      analysis of human movement. However, previous methods of motion measurement using
      goniometry and surface markers have several associated problems: goniometers
      constrain human motion; and surface markers are missed, etc. To resolve these
      problems, a new technique of motion measurement using image processing is
      proposed. In this method, movements of the whole body are captured as image
      information, and a geometric model of a human body is fitted onto the contours of
      the image sequences. The joint angles are then estimated from the model. Usually,
      every segment has to be coloured separately so as to fit the geometric model
      automatically into the images; furthermore, this takes a very long time to
      process. Therefore, we reduced the processing time using the information in the
      overlap area between the models and images, instead of contour information. We
      estimated the joint angles of hidden segments with the grey scale image
      information. Thus there is no need to colour segments and attach surface markers;
      and unconstrained motion can be measured. Using the method developed, three
      dimensional motion of the fingers including 21 segments was measured in 3-5 min
      per frame by a personal computer. The errors are 2 degrees maximally.

PMID- 8143695
TI  - Workload and psychophysiological stress reactions in air traffic controllers.
AB  - Interactions between workload and psychophysiological stress symptoms were
      investigated in a population of 205 predominantly male air traffic controllers
      (ATCs) from the area control centre (ACC) and the airport control tower (TWR) in
      Zurich and Geneva. Each subject completed two questioning sessions and two
      working sessions, the first time during a period of low traffic and the second
      time during a period of high traffic. For the questioning sessions standardized
      questionnaires were used. For all investigated working sessions, different
      aspects of the subjective and objective workload were recorded. Before and after
      each session, a saliva sample for assessing the concentration of secreted
      cortisol was taken. The questionnaire parameters represented psychological stress
      symptoms, such as complaints of physical discomfort, depression, negative self
      communication, work-increased anxiety, coping behaviour and subjective rating,
      and interpretation of various aspects of the working situation. The mean values
      measured were within the normal range, and only a few significant differences
      between the two questioning sessions were found. However, about 10 to 15% of the
      ATCs showed elevated values in psychological stress symptoms to an extent
      indicating that they might have serious stress problems at work and/or in their
      private life. The investigated working sessions showed that the ATCs' subjective
      ratings correspond clearly to their cortisol response and the objective workload.
      Thus, ATCs' complaints regarding excess work stress should be taken seriously.

PMID- 8143696
TI  - The effects of variation in body temperature on the preferred water temperature
      and flow rate during showering.
AB  - The purpose of this study was to investigate the effects of body temperature
      variations on subjects' preferred water temperature and flow rate during showers.
      Nine healthy women students took a shower before and after physical exercise
      (running on a treadmill for 30 min) and water immersion (immersing in the water
      of 25 degrees C temperature for 30 min). During each shower, the subject was
      instructed to adjust both the water temperature and flow rate of a shower to suit
      their comfort. Rectal temperature and skin temperatures of the subjects, water
      temperature, and flow rate of the shower were measured during the experiments.
      The means of preferred water temperature during showers were 40.2 degrees C and
      43.8 degrees C before and after water immersion respectively, which were
      significantly different. On the other hand, there was little difference in the
      preferred water temperature between before and after the treadmill exercise.
      There were no significant differences in the flow rates between before and after
      both water immersion and the treadmill exercise. A significant negative
      relationship was observed between the mean body temperature (Tb) and the
      preferred water temperature during showers (r = -0.439). On the other hand, no
      significant relationship was found between Tb and the preferred flow rate.
      Moreover, a significant negative relationship was observed between the preferred
      water temperature and the flow rate during showers (r = -0.528).

PMID- 8143697
TI  - Assay by inhibition of repair to measure O6-methylguanine in DNA.
AB  - A procedure for measuring the level of O6-methylguanine (O6-meG) in DNA is
      described. Repair of 32P-oligodeoxynucleotides containing O6-meG adducts by O6
      alkylguanine alkyltransferase (AGT) was performed in the presence of different
      quantities of DNA containing unknown concentrations of O6-meG. Each methylated
      DNA sample inhibited the repair of oligodeoxynucleotide substrate to an extent
      dependent upon O6-meG concentration. Each DNA sample tested at different
      concentrations in the assay therefore had a characteristic inhibition curve and
      could be compared to the curves generated using reference DNA samples of known O6
      meG concentration. We report the method of calculation of the O6-meG level in a
      given DNA sample by comparison of its inhibition curve with that of reference
      DNAs. This method of calculation does not require a knowledge of the exact
      quantity of the labelled substrate or AGT used. The method requires only 0.1-10
      micrograms of DNA, with a limit of detection of 0.8 fmol of O6-meG per microgram
      of DNA.

PMID- 8143698
TI  - Differential effects of luminol, nickel, and arsenite on the rejoining of
      ultraviolet light and alkylation-induced DNA breaks.
AB  - When Chinese hamster ovary cells were treated with ultraviolet (UV) light or
      methyl methanesulfonate (MMS), a large number of DNA strand breaks could be
      detected by alkaline elution. These strand breaks gradually disappeared if the
      treated cells were allowed to recover in a drug-free medium. The presence of
      nickel or arsenite during the recovery incubation retarded the disappearance of
      UV-induced strand breaks, whereas the disappearance of MMS-induced strand breaks
      was retarded by the presence of arsenite or of luminol, a new inhibitor for
      poly(ADP-ribose) synthetase. Luminol, however, had no apparent effect on the
      repair of UV-induced DNA strand breaks, and nickel had no effect on the repair of
      MMS-induced DNA strand breaks. When UV- or MMS-treated cells were incubated in
      cytosine arabinofuranoside (AraC) plus hydroxyurea (HU), a large amount of low
      molecular weight DNA was detected by alkaline sucrose sedimentation. The
      molecular weight of these DNAs increased if the cells were further incubated in a
      drug-free medium. This rejoining of breaks in cells pretreated with UV plus AraC
      and HU was inhibited by nickel and by arsenite, but not by luminol. The rejoining
      of breaks in cells pretreated with MMS plus AraC and HU was inhibited by luminol
      and by arsenite, but not by nickel. These results suggest that different enzymes
      may be used in DNA resynthesis and/or ligation during the repairing of UV- and
      MMS-induced DNA strand breaks, and that nickel, luminol, and arsenite may have
      differential inhibitory effects on these enzymes.

PMID- 8143699
TI  - 32P-postlabelling analysis of DNA adducts in white blood cells of humans exposed
      to residential wood combustion particulate matter.
AB  - Residential wood combustion (RWC) in open fireplaces poses a possible health risk
      because of the emission into the indoor air of mutagenic and carcinogenic
      compounds. In the present report it was investigated whether this emission leads
      to enhanced levels of DNA adducts in white blood cells (WBC) of exposed subjects.
      Under conditions that most likely reflect the Dutch pattern of use of open
      fireplaces, RWC increased both indoor air mutagenicity and levels of
      benzo(a)pyrene (B(a)P) and pyrene. The indirect mutagenicity showed a stronger
      increase than the direct mutagenicity. The increase in indirect mutagenicity was
      not directly correlated with the increase in the levels of B(a)P and pyrene. 32P
      postlabelling analysis of DNA adducts following nuclease P1 enrichment or butanol
      extraction revealed low adduct levels. No combustion-related increase in the
      amount of adducts was observed. Possible explanations for the lack of correlation
      between air monitoring data and WBC DNA adduct levels are discussed.

PMID- 8143700
TI  - Negative dose-response relationship for radiation-induced micronuclei in
      polychromatic erythrocytes of mice.
AB  - Micronuclei were assessed among the bone marrow PCEs of mice 28 hr after
      exposures to 1 to 8 Gy of X-rays and at 6-hr intervals from 12-60 hr after
      exposures to 2 or 6 Gy. At 28 hr, the frequency of micronuclei declined as the
      exposure level increased from 1 to 8 Gy. The peak proportion of micronucleated
      PCEs appeared much later following 6 Gy than after 2 Gy exposures, implicating
      cell cycle delay as the cause of the negative dose-response relationship.

PMID- 8143701
TI  - Lack of chloroform-induced DNA repair in vitro and in vivo in hepatocytes of
      female B6C3F1 mice.
AB  - Chloroform has been shown to induce hepatocellular carcinomas in female B6C3F1
      mice when administered by gavage, but not when given in drinking water. When
      administered in corn oil at the carcinogenic doses of 238 and 477 mg/kg,
      chloroform induced necrosis and sustained regenerative cell proliferation in the
      liver. To investigate the mode of action of tumor induction in the target cells,
      the ability of chloroform to induce unscheduled DNA synthesis (UDS) was examined
      in the in vitro and in vivo hepatocyte DNA repair assays. In the in vitro assay,
      primary hepatocyte cultures from female B6C3F1 mice were incubated with
      concentrations from 0.01 to 10 mM chloroform in the presence of 3H-thymidine. UDS
      was assessed by quantitative autoradiography. No induction of DNA repair was
      observed at any concentration. In the in vivo assay, animals were treated by
      gavage with 238 and 477 mg/kg chloroform in corn oil. Primary hepatocyte cultures
      were prepared 2 and 12 hr later, incubated with 3H-thymidine, and assessed for
      induction of UDS as above. No DNA repair activity was seen at either dose or at
      either timepoint. These negative results in the target organ are consistent with
      the concept that neither chloroform nor its metabolites are directly DNA reactive
      and that the carcinogenicity of chloroform is secondary to induced cytolethality
      and regenerative cell proliferation.

PMID- 8143702
TI  - Chromosome aberration, sister-chromatid exchange, proliferative rate index, and
      serum thiocyanate concentration in smokers exposed to low-dose benzene.
AB  - Cytogenetical endpoints, i.e., chromosome aberration (CA), sister-chromatid
      exchange (SCE), and proliferative rate indexes (PRI), were measured in peripheral
      blood lymphocytes (PBL) of 42 workers exposed occupationally to low-dose benzene,
      and of 42 controls. The role of smoking habit as a confounding factor of
      genotoxic effects caused by occupational low-dose benzene exposure was also
      studied. The benzene concentrations in the ambient air samples varied from 3 to
      20 mg/m3 (mean: 7 mg/m3). The continuous low-dose benzene exposure significantly
      increased the CA and SCE frequencies, but did not influence PRI. Smoking levels
      were characterized by subjective accounts and by serum thiocyanate concentrations
      (SCN). CA and SCE were not significantly increased in smokers compared to
      nonsmokers, but the differences were expressed to a greater extent in the case of
      measurement of SCN concentrations. Determination of SCN proved to be more
      objective in the assessment of genotoxic effects of smoking as a confounding
      factor of occupational low-dose benzene exposure.

PMID- 8143703
TI  - Studies on cytotoxic and genotoxic effects of cadmium nitrate and lead nitrate in
      Chinese hamster ovary cells.
AB  - Cadmium nitrate decreased the viability of Chinese hamster ovary (CHO) cells in a
      concentration-dependent manner; 50% inhibition (IC50) was achieved at 0.015 mM.
      In contrast, lead nitrate appeared to be less toxic. Neither cadmium nitrate nor
      lead nitrate significantly increased frequencies of binucleated CHO cells with
      micronuclei (MN). However, both cadmium nitrate and lead nitrate could augment
      sister chromatid exchanges (SCEs). Cadmium nitrate induced SCEs with a potency
      approximately equal to that of mitomycin C and more than 10 times higher than
      lead nitrate. Cadmium nitrate also increased chromosome aberrations (CAs), which
      included breaks, acentrics, interchanges, and dicentrics of chromosomes. In
      addition, cadmium nitrate induced a decrease in the mitotic index (MI), but lead
      nitrate increased it. In summary, it appears that both of these two heavy metal
      salts have cytogenetic toxicities with different degrees of effects on the
      cytotoxicity, MN, CAs, and SCEs in CHO cells. However, SCE was the most sensitive
      endpoint for indicating mutagenetic effects of cadmium and lead in the present
      study.

PMID- 8143704
TI  - Procedure for reduction of test chemical requirement in preliminary assays using
      the L5178Y TK+/- mouse lymphoma forward mutation assay.

PMID- 8143705
TI  - Mutant alleles of tRNA(Thr) genes suppress the hisG46 missense mutation in
      Salmonella typhimurium.
AB  - Extragenic suppressors of the hisG46 missense mutation were mapped to the 71 and
      88 min regions of the Salmonella typhimurium chromosome, positions that in
      Escherichia coli contain the thrV (tRNA(Thr1)) and thrT (tRNA(Thr3)) genes,
      respectively. The suppressor loci were identified as mutant alleles of thrV and
      thrT, using allele-specific colony hybridization. An oligomer, based on the
      conserved 5' sequence of the thrT and thrV genes in E. coli and designed to
      contain the putative mutant anticodon, discriminated between suppressor
      containing and wild-type strains. Similarly, probes specific for the thrV[SuGGG]
      and thrT[SuGGG] were used to differentiate the two suppressors. To date, all
      extragenic suppressors of hisG46 have been identified as either thrV[SuGGG] or
      thrT[SuGGG]. A near equal distribution of thrV[SuGGG] and thrT[SuGGG] suppressors
      was found among 29 spontaneous and 43 mutagen-induced hisG46 extragenic
      suppressor revertants. It was concluded, therefore, that mutant alleles of thrV
      and thrT are predominantly, if not solely, responsible for intergenic suppression
      of the hisG46 mutation.

PMID- 8143706
TI  - Multiplex PCR analysis of in vivo-arising deletion mutations in the hprt gene of
      human T-lymphocytes.
AB  - A multiplex polymerase chain reaction (PCR) procedure was adapted for the rapid
      and efficient evaluation of deletions of the hypoxanthine guanine
      phosphoribosyltransferase (hprt) gene in human T-lymphocytes. The hprt clonal
      assay was used to isolate in vivo-arising hprt-deficient T-cells from six healthy
      males. Mutant frequencies ranged from 9-27 x 10(-6). Simple crude cellular
      extracts from 223 mutants were analyzed for hprt gene deletion. Sixteen (7.2%)
      were found to be due to total gene deletion and 22 (9.9%) were due to partial
      gene deletion. The relatively high frequency of total gene deletions was caused
      by replicate isolates of a single mutational event as shown by single-strand
      conformation polymorphism (SSCP) analysis of rearranged T-cell receptor (TCR)
      gamma genes. Eighteen of the 22 partial hprt gene deletion mutants were
      determined to be of independent origin based on a unique hprt mutation or SSCP
      TCR -gamma pattern. One-half (9/18) of the partial deletion mutants involved all
      or part of exon 4 alone, suggesting that this region of the hprt gene is prone to
      deletion. The small deletions effecting exon 1 (1 mutant), exon 2 (2 mutants),
      and exon 4 (6 mutants) would not have been detected by conventional Southern blot
      analysis and may represent a new, previously unrecognized class of mutations. The
      ready isolation of such intragenic deletions will allow the characterization of
      breakpoint junctions and may provide insights into the important processes of DNA
      breakage and rejoining.

PMID- 8143708
TI  - Mechanical ventilation in acute respiratory failure.

PMID- 8143707
TI  - Mutational spectrum of ICR-191 at the hprt locus in human lymphoblastoid cells.
AB  - Human TK6 lymphoblasts were treated with the acridine derivative ICR-191, and
      mutants at the hprt locus were isolated. Mutant hprt cDNA was reverse-transcribed
      from mRNA, amplified by polymerase chain reaction (PCR), and sequenced. Additions
      of single G:C base pairs (+1 frameshift mutations) in repetitive G:C sequences
      were found in 82% (32/39) of the mutants. Sixteen of the +1 frameshifts analyzed
      were located in a single sequence of six consecutive guanine bases in exon 3. The
      remaining +1 frameshifts occurred at six different GGG sequences (14 mutants) and
      a single GGGG sequence (2 mutants) in other hprt exons. The repetitive guanine
      sequences that underwent frameshift mutagenesis were located in both the
      transcribed and nontranscribed strands of hprt. No single base deletions (-1
      frameshift mutations) were observed. Base substitutions were observed in 13%
      (5/39) of the clones analyzed and occurred at both G:C and A:T bases. Loss of
      exon 4 from the cDNA was also observed in 5% (2/39) of the mutants. Hprt mutants
      containing seven consecutive guanines (produced from a +1 frameshift in a GGGGGG
      sequence) were treated with ICR-191 and wild-type revertants selected in CHAT
      medium. Revertants were recovered at a frequency of approximately 10(-7) and
      contained the wild-type sequence (GGGGGG) in all clones analyzed. The observed
      frequency of ICR-191-induced-1 frameshift reversion in the GGGGGGG sequence was
      approximately 500-fold lower than the estimated frequency of +1 frameshifts
      observed in the wild-type GGGGGG sequence following the same ICR-191 treatment.
      These results suggest that ICR-191 produces predominantly +1 frameshift mutations
      at the hprt locus in human cells.

PMID- 8143709
TI  - Basic mechanisms and clinical consequences of cyclic changes in pulmonary blood
      flow and blood volume during mechanical ventilation.
AB  - One of the main functions of the pulmonary circulation is its capacity function,
      including its function as a reservoir of blood. Changes in pulmonary blood volume
      occur if the input (right ventricular output) and the output (left ventricular
      output) of the pulmonary circulation are different. Transient differences between
      the input and the output occur during each ventilatory cycle of mechanical
      ventilation due to changes in intrathoracic pressure and consequent changes in
      central venous pressure. The haemodynamic effects of these transient changes in
      input and output and their dependence on the volaemic condition have been reduced
      to basic physiological mechanisms. The consequences have been extrapolated to
      clinical conditions.

PMID- 8143710
TI  - Dynamic hyperinflation and intrinsic PEEP during mechanical ventilation.
AB  - Dynamic hyperinflation, also called intrinsic PEEP (PEEPi,) occurs particularly
      when high tidal volumes or high respiratory rates are used during mechanical
      ventilation, although the phenomenon does occur at normal tidal volumes. It is
      not identified using existing monitoring such as the airway pressure but can be
      identified by occlusion of the expiratory port before the onset of the next
      positive pressure breath. Many factors contribute to PEEPi which has unfavourable
      effects on respiratory muscle activity. Inhomogenicity of the time constants is a
      major aetiological factor. Fine tuning of positive pressure ventilation, using
      low tidal volumes, short inspiratory times and adequate inspired oxygen are
      required. External PEEP, up to but not exceeding PEEPi, may be advisable. PEEP
      may be used therapeutically to improve gas exchange by inverse ratio ventilation
      or high frequency jet ventilation.

PMID- 8143711
TI  - Inspiratory pressure support.
AB  - Inspiratory pressure support is a mode of partial ventilatory support which can
      be defined as patient-initiated, pressure-targeted and patient-interrupted.
      Addition of pressure support to a spontaneously breathing patient results in a
      reduction of respiratory rate and an increase in tidal volume. It corrects
      arterial blood gas abnormalities resulting from rapid shallow breathing and
      reduces the work of breathing. The synchrony between the patient's demand and
      ventilator assistance is optimized and allows an improvement in the efficiency of
      the spontaneous effort of the patient. Since it is not volume-targeted, variation
      in delivered ventilation may occur in unstable patients or in patients with
      fluctuations in respiratory drive. Clinical advantages have been found using
      pressure support during the process of weaning from mechanical ventilation in
      patients with prolonged difficulty in tolerating discontinuation from mechanical
      ventilation. Lastly, it can be delivered via a face-mask to avoid the need for
      endotracheal intubation in patients with hypercapnic respiratory failure.

PMID- 8143712
TI  - Biphasic positive airway pressure (BIPAP)--a new mode of ventilatory support.
AB  - Biphasic Positive Airway Pressure (BIPAP) can be described as pressure controlled
      ventilation in a system allowing unrestricted spontaneous breathing at any moment
      of the ventilatory cycle. It can also be described as a Continuous Positive
      Airway Pressure (CPAP) system with a time-cycled change of the applied CPAP
      level. As with a pressure controlled, time-cycled mode, the duration of each
      phase (T(high), T(low)) as well as the corresponding pressure levels (P(high),
      P(low)) can be adjusted independently. Depending on the spontaneous breathing
      activity, BIPAP can be subdivided into: no spontaneous breathing: CMV-BIPAP;
      spontaneous breathing at the lower pressure level: IMV-BIPAP; spontaneous
      breathing at the upper pressure level: APRV-BIPAP; spontaneous breathing at both
      CPAP levels: genuine BIPAP. Since it enables progressive transition from
      controlled to all levels of augmented mechanical ventilation, BIPAP appears to be
      a suitable mode for the entire period of mechanical ventilation of the patient.
      There are difficulties neither in choosing the correct moment for switching nor
      the further respiratory management of the ventilated patient under BIPAP. The
      necessary adaptation (ventilation, oxygenation) can be individualized on the
      basis of blood gas analyses. An increase or reduction of the invasivity of
      ventilation can be attained without any problems with BIPAP. Furthermore,
      spontaneous breathing of the patient does not necessitate any switching of the
      mode of ventilation. The transition from controlled to augmented ventilation is
      smooth. BIPAP enables the therapist to let the patient breathe freely even under
      the most invasive ventilation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143713
TI  - Inhalation of nitric oxide--a new approach in severe ARDS.
AB  - Pulmonary hypertension due to increased pulmonary vascular resistance, and
      hypoxaemia based on an elevated intrapulmonary shunt are important
      pathophysiological features of the adult respiratory distress syndrome (ARDS).
      Systemically infused vasodilators reduce pulmonary hypertension but also decrease
      mean systemic arterial pressure and impair pulmonary gas exchange because of
      their global vasodilatory effects on the systemic and pulmonary circulation.
      Recently, inhaling low concentrations of the gas nitric oxide (NO), an important
      endothelium-derived relaxing factor which is rapidly inactivated by binding to
      haemoglobin, has been shown to induce selective vasodilation of ventilated lung
      regions. Thus, inhaled NO reduces pulmonary hypertension in severe ARDS and
      improves arterial oxygenation by redistributing blood flow away from areas with
      intrapulmonary shunt to areas with a normal ventilation/perfusion ratio.

PMID- 8143714
TI  - Pulmonary gas exchange in acute respiratory failure.
AB  - The principal function of the lung is to facilitate the exchange of the
      respiratory gases, oxygen (O2) and carbon dioxide (CO2). When the lung fails as a
      gas exchanger respiratory failure ensues. Clinically, it is generally accepted
      that an arterial oxygen tension (PaO2) of less than 60 mmHg or a PaCO2 of greater
      than 50 mmHg, or both, whilst breathing room air are values consistent with the
      concept of respiratory failure. This article will deal, firstly, with some basic
      aspects of the physiology of pulmonary gas exchange and more specifically on the
      measurement of ventilation-perfusion (VA/Q) relationships, the most influential
      factor determining hypoxaemia. The second part highlights the most important
      findings on pulmonary gas exchange in the adult respiratory distress syndrome
      (ARDS) and other common acute respiratory failure conditions, such as pneumonia,
      acute exacerbation of chronic obstructive pulmonary disease (COPD) and status
      asthmaticus, based on the data obtained by means of the multiple inert gas
      elimination approach, a technique which gives a detailed picture of VA/Q ratio
      distributions.

PMID- 8143715
TI  - Artificial ventilation: some unresolved problems.
AB  - In acute respiratory failure interstitial oedema, alveolar collapse, and multiple
      atelectasis are the main mechanisms which lead to increased venous admixture and
      impaired oxygenation. Thus the lung volume available for pulmonary gas exchange
      is considerably reduced. Since there is strong evidence that alveolar
      overdistension causes lung damage ('barotrauma/volutrauma') large tidal volumes
      and high airway pressures in mechanical ventilation have to be strictly avoided,
      even allowing hypoventilation ('permissive hypercapnia'). Recruitment of the
      collapsed alveoli by external or intrinsic PEEP, or by changing body position, is
      often possible. However, alveolar recruitment takes much longer than previously
      assumed: instead of occurring within one respiratory cycle ('inflection point'),
      it seems to take hours. This slow recruitment process can be effectively
      supported by a deliberate use of intrinsic PEEP as with inverse ratio
      ventilation, either in volume or pressure controlled mode. Assisted spontaneous
      breathing makes ventilatory support less invasive and offers considerable
      advantages for many patients, but there are still some restrictions. Individual
      adaptation may be difficult in some patients. New principles of assistance
      control ('proportional assist ventilation') may improve individual adaptation.
      New concepts for weaning in COPD patients seem to offer better clinical
      strategies.

PMID- 8143716
TI  - All potential glycosylation sites of the nicotinic acetylcholine receptor delta
      subunit from Torpedo californica are utilized.
AB  - All possible N-glycosylation sites of the delta subunit of the nicotinic
      acetylcholine receptor from Torpedo californica electric tissue are utilized. By
      a combination of microsequencing and mass spectrometry, it was shown that a high
      mannose-type oligosaccharide is bound at Asn143 of the delta subunit. The
      oligosaccharides at positions Asn70 and Asn208 of the delta subunit are probably
      of the complex type. The utilized glycosylation sites pose restrictions on
      possible transmembrane folding models of the subunit.

PMID- 8143717
TI  - Photolabeling of soybean microsomal membrane proteins with photoreactive acyl-CoA
      analogs.
AB  - Synthesis of 32P-labeled 12-azidooleoyl-CoA and 125I-labeled 12
      [(azidosalicyl)amino]dodecanoyl-CoA (ASD-CoA) was achieved. The synthesized
      radioactive, photoreactive reagents were tested as photoaffinity labels for acyl
      CoA:lysophosphatidylcholine acyltransferase from the microsomal membranes of
      developing soybean cotyledons. When a mixture of microsomal membranes and the
      azidooleoyl-CoA or ASD-CoA were incubated in the dark, the analogs were
      recognized as substrate and competitive inhibitor, respectively. The enzyme
      preferentially utilizes unsaturated acyl-CoAs rather than saturated acyl-CoAs.
      Incubation of microsomal membranes with acyl-CoA analogs and immediately followed
      by photolysis resulted in an irreversible inhibition of lysophosphatidylcholine
      acyltransferase activity. Analysis of photolyzed microsomal membranes by SDS/PAGE
      and autoradiography revealed that azidooleoyl-CoA preferentially labeled eight
      acyl-CoA binding proteins, but ASD-CoA labeled only three polypeptides with
      molecular masses of 110, 90 and 32 kDa that are commonly labeled by both the
      analogs. Oleoyl-CoA and dodecanoyl-CoA protect the enzyme against
      photoinactivation by azidooleoyl-CoA and ASD-CoA, respectively. The protection
      was profound in 110-kDa polypeptide indicating that this protein could be
      lysophosphatidylcholine acyltransferase. These results demonstrate that the
      photoaffinity of acyl-CoA analogs makes them potential probes to identify and
      characterize lipid biosynthetic enzymes.

PMID- 8143718
TI  - Phospholipid binding and transfer by the nonspecific lipid-transfer protein
      (sterol carrier protein 2). A kinetic model.
AB  - The nonspecific lipid-transfer protein (nsL-TP) from bovine liver was studied by
      measuring the binding and transfer of the fluorescent phospholipid 1-palmitoyl-2
      [6-(1-pyrenyl)-hexanoyl]-sn-glycero-3-phosphocholine (PamPryGroPCho). A kinetic
      model is presented involving three steps: (a) interaction of nsL-TP with a
      membrane surface; (b) equilibration of PamPyrGroPCho monomers between the
      membrane and nsL-TP; and (c) dissociation of the nsL-TP/PamPyrGroPCho complex
      from the membrane surface. Steady-state analysis of the model yielded theoretical
      equations describing both binding and transfer kinetics. Computer analysis, using
      these equations, showed good fits with the experimental results and several
      kinetic constants could be calculated. From these constants it was inferred that
      incorporation of acidic phospholipids into vesicles enhanced the interaction of
      nsL-TP with the membrane interface (step a), without affecting the equilibrium
      binding of phospholipid monomers to nsL-TP (step b). As a result, the rate of nsL
      TP-mediated PamPyrGroPCho transfer from donor to acceptor vesicles was greatly
      affected. Under the conditions of incubation, incorporation of the acidic lipids
      in the donor membrane vesicles stimulated transfer, whereas incorporation of
      these lipids in the acceptor membranes could lead to a virtually complete
      inhibition of transfer. From the results it is concluded that the formation of a
      soluble lipid-nsL-TP complex is the key step in nsL-TP-mediated phospholipid
      transfer.

PMID- 8143719
TI  - Regulation of the erythrocyte Ca(2+)-ATPase at high pH.
AB  - The activation of the Ca(2+)-ATPase from erythrocyte membranes at high pH has
      been investigated. Following alkalinization and in the absence of regulators, the
      enzyme exhibits a very high affinity for Ca2+ and a decreased maximal velocity.
      Either addition of calmodulin, addition of acidic phospholipids, or controlled
      trypsinization decreases the concentration of effector required to elicit half
      maximal activation of the enzyme for calcium to similar values. The increase in
      affinity for Ca2+, however, is smaller than that observed at neutral pH. The
      maximal velocity at high pH becomes insensitive to both calmodulin and controlled
      proteolysis, although calmodulin binds to the protein with similar affinities at
      pH 7.0 and 8.0, as indicated by similarity in binding to a calmodulin-Sepharose
      resin and in dependence on calmodulin concentrations when the pH is increased. In
      contrast to the attenuated effects of calmodulin and proteolysis, at pH 8.0 the
      enzyme is susceptible to stimulation by phospholipids, indicating that the
      pathway for transduction of the signal from phospholipids is distinct from that
      pathway engaged by calmodulin and/or trypsinization. At pH 8.0,
      phosphatidylinositol induces the modulatory effect of ATP at the regulatory site
      but calmodulin does not. We suggest that the intraenzymic connection between the
      calmodulin-binding, autoinhibitory peptide and the nucleotide domain of the
      enzyme is impaired upon alkalinization, which would account for the differing
      abilities of the activators to modulate the ATP effects.

PMID- 8143721
TI  - Evidence that the recently discovered high-energy nucleotide derivative,
      oligo(phosphoglyceroyl-ATP) forms the end chains of purinogen, a complex
      polymeric major storage form of adenine nucleotide and phosphate in heart.
AB  - Previous work in our laboratory has shown that free adenine nucleotides in heart,
      liver and kidney exchange rapidly with a major acid-insoluble species which we
      have characterised as oligo[3-phospho-glyceroyl-gamma-
      triphospho(5')adenosine(3')], abbreviated to (PG-ATP)n. This has been found in
      liver and in heart to be complexed to a specific 3'-phosphodiesterase which
      releases PG-ATP monomers and is located in mitochondrial inter-membrane space. In
      [14C]adenosine-perfused hearts, (PG-ATP)n has been shown to reach specific
      radioactivity equilibrium with free ATP within 30 min. Attempts to estimate the
      quantities of nucleotide in (PG-ATP)n and free nucleotides in response to a
      variety of stimuli using previously labelled hearts showed by contrast that the
      free and sequestered nucleotide pools were not at equilibrium. Re-examination of
      the rapidly labelled acid-insoluble species led to the recognition of radioactive
      inhomogeneity and of three additional nucleotide components. Perfusion of hearts
      with phosphate-free medium increased the proportion of 14C incorporated into the
      sequestered from by 70% and caused the net transfer of 0.9 mumol.g-1 of purine
      from free adenine nucleotides to the sequestered form. The findings point to the
      existence of a more complex polymer whose rapidly exchanging end chains we had
      previously isolated and characterised as (PG-ATP)n; we suggest the name purinogen
      for this polymer and show that it can contain between 25% and 55% of the tissue
      nucleotide pool in rat heart.

PMID- 8143720
TI  - X-ray crystal structures of cytosolic glutathione S-transferases. Implications
      for protein architecture, substrate recognition and catalytic function.
AB  - Crystal structures of cytosolic glutathione S-transferases (EC 2.5.1.18),
      complexed with glutathione or its analogues, are reviewed. The atomic models
      define protein architectural relationships between the different gene classes in
      the superfamily, and reveal the molecular basis for substrate binding at the two
      adjacent subsites of the active site. Considerable progress has been made in
      understanding the mechanism whereby the thiol group of glutathione is
      destabilized (lowering its pKa) at the active site, a rate-enhancement strategy
      shared by the soluble glutathione S-transferases.

PMID- 8143722
TI  - Redox control of beta-oxidation in rat liver mitochondria.
AB  - Coupled rat liver mitochondria were incubated with [U-14C]hexadecanoate and
      carnitine which resulted in the formation of acyl-, 2-enoyl- and 3-hydroxyacyl
      CoA and carnitine esters. The production of 2-enoyl-CoA and 3-hydroxyacyl-CoA
      esters was associated with a significant lowering of the NAD+/NADH ratio, in
      contrast to rat muscle mitochondria [Eaton, S., Bhuiyan, A. K. M. J., Kler, R.
      S., Turnbull, D. M. & Bartlett, K. (1993) Biochem. J. 289, 161-172], suggesting
      that control by the respiratory chain is important under normal conditions. When
      NAD+/NADH ratios were held low by succinate-induced reverse electron flow, 3
      enoyl-CoA esters were also detected, probably formed by the action of 3,2-enoyl
      CoA isomerase. Measurement of the flux of beta-oxidation at different
      osmolalities showed that flux was strongly dependent on osmolality changes in the
      physiological range. Measurement of the CoA and carnitine esters resulting from
      incubations made at different osmolalities showed that there was an increase in
      the amounts of the saturated acyl-CoA esters with respect to 2-enoyl-CoA and 3
      hydroxyacyl-CoA esters, consistent with control by the electron-transfer
      flavoprotein-ubiquinone segment [Halestrap, A. P. & Dunlop, J. L. (1986) Biochem.
      J. 239, 559-565]. This however could not be the only factor operating as
      indicated by the continued presence of 2-enoyl-CoA and 3-hydroxyacyl-CoA esters
      at high osmolalities.

PMID- 8143723
TI  - Regulation of transferrin receptor mRNA expression. Distinct regulatory features
      in erythroid cells.
AB  - In proliferating non-erythroid cells, the expression of transferrin receptors
      (TfR) is negatively regulated by the amount of intracellular iron. Fe-dependent
      regulation of TfR occurs post-transcriptionally and is mediated by iron
      responsive elements (IRE) located in the 3' untranslated region of the TfR mRNA.
      IREs are recognized by a specific cytoplasmic binding protein (IRE-BP) that, in
      the absence of Fe, binds with high affinity to TfR mRNA, preventing its
      degradation. While TfR numbers are positively correlated with proliferation in
      non-erythroid cells, in hemoglobin-synthesizing cells, their numbers increase
      during differentiation and are, therefore, negatively correlated with
      proliferation. This suggests a distinct regulation of erythroid TfR expression
      and evidence, as follows, for this was found in the present study. (a) With
      nuclear run-on assays, our experiments show increased TfR mRNA transcription
      following induction of erythroid differentiation of murine erythroleukemia (MEL)
      with Me2SO. (b) Me2SO treatment of MEL cells does not increase IRE-BP activity
      which is, however, increased in uninduced MEL cells by Fe chelators. (c)
      Following induction of MEL cells, there is an increase in the stability of TfR
      mRNA, whose level is only slightly affected by iron excess. (d) Heme-synthesis
      inhibitors, such as succinylacetone and isonicotinic acid hydrazide, which
      inhibit numerous aspects of erythroid differentiation, also inhibit TfR mRNA
      expression in induced MEL cells. However, heme-synthesis inhibition does not lead
      to a decrease in TfR mRNA levels in uninduced MEL cells. Thus, these studies
      indicate that TfR gene expression is regulated differently in hemoglobin
      synthesizing as compared to uninduced MEL cells.

PMID- 8143725
TI  - Thermodynamic stability and solution conformation of tandem G.A mismatches in RNA
      and RNA.DNA hybrid duplexes.
AB  - G.A mismatches form a variety of hydrogen-bonded structures in DNA, most of which
      destabilise the duplex. Tandem G.A mismatches in the context YGAR (Y =
      pyrimidine, R = purine), however, form base pairs using the amino group of the
      guanine residue [Li, Y., Zon. G. & Wilson, W.D. (1991) Proc. Natl Acad. Sci. USA
      88, 26-30], which permits extensive base-base stacking, leading to a slight
      stabilisation of the helix [Ebel, S., Lane, A. N. & Brown, T. (1992) Biochemistry
      31, 12083-12086]. We have measured the thermodynamic stability of several RNA and
      RNA.DNA hybrid duplexes containing tandem G.A mismatches. The RNA duplexes are
      intrinsically much more stable than the corresponding DNA duplexes and the
      mutations are destabilising in all cases. NOE and coupling-constant data show
      that all of the sugars are in the C3'-endo range of conformations, and glycosidic
      torsion angles are in the range -160 degrees to -180 degrees in [sequence: see
      text]. Both sequential NOE intensities and circular-dichroism measurements
      indicate that the global conformation of the mismatched RNA is A-like. The N1H
      group of the mismatched guanine residue is not involved in hydrogen bonding with
      the adenine residue, indicating the presence of the amino-pairing scheme.
      Determination of the structure using 'loose' NMR-derived constraints shows that
      the potential energies of the imino-paired and amino-paired forms are similar,
      but substantially higher than energy-minimised RNA. Using tighter constraints
      derived from more extensive analysis of one-dimensional and two-dimensional NOE
      data showed that the amino-paired structure agrees with the constraint data
      better than the imino-paired structure, and also accounts for unusual chemical
      shifts and the lack of hydrogen bonding of the guanine N1H group. Resulting
      molecular models show that the amino-paired mismatches are not as extensively
      stacked on the neighbouring part of the duplex as in the B-DNA analogues, largely
      accounting for the lower thermodynamic stability in the RNA duplexes.

PMID- 8143724
TI  - Isolation and expression of a gene specifying a cdc2-like protein kinase from the
      human malaria parasite Plasmodium falciparum.
AB  - A partially redundant oligonucleotide based on conserved protein sequences of cdk
      and cdc2-like proteins was used to isolate from genomic libraries of Plasmodium
      falciparum fragments of chromosome XIII carrying a 288-residue open-reading frame
      encoding a protein kinase sharing 57-58% identity with yeast p34cdc2. Based on
      sequence data, base composition and the striking similarity with other cdk and
      related proteins, four intervening sequences were identified. Their removal in
      vitro allowed expression of the gene, designated PfPK5, in Escherichia coli, the
      resulting product having kinase activity against casein and histone H1. Western
      blotting using a polyclonal antibody raised against the expressed protein showed
      that the kinase was located in the parasite's cytosol and was present in
      approximately constant amounts throughout the intra-erythrocytic asexual
      reproductive stage of the life cycle. The PSTAIRE region of the PfPK5 protein
      differs at three sites from that of p34cdc2, and the gene failed to complement
      cdc2/28 yeast mutants. However, Western blotting showed that the gene was not
      expressed in yeast, so this does not eliminate the possibility that it is the
      malarial version of cdc2.

PMID- 8143726
TI  - Properties of multiple G.A mismatches in stable oligonucleotide duplexes.
AB  - The solution structure of the deoxydecanucleotide [sequence: see text] has been
      determined by NMR methods. This duplex, which contains six G.A mismatches and
      four Watson-Crick base pairs, is thermodynamically more stable than a decamer
      where T.A base pairs are substituted for the G.A mismatches, and is less stable
      than the duplex that contains G.C base pairs. Circular-dichroism spectroscopy
      indicates an overall B-like conformation for the decamer, but stronger than usual
      base stacking. 1H-NMR spectroscopy revealed that the N1H groups of the mismatched
      guanine residues are not hydrogen bonded, and 31P-NMR showed the presence of BII
      phosphate conformations for the GpA steps. Detailed analysis of the NMR data
      showed that all nucleotides have anti glycosidic torsion angles and S type sugar
      puckers. The G.A mismatches pair in the amino form as originally proposed by Li
      et al. [Li, Y., Zon, G. & Wilson, W. D. (1991) Proc. Natl Acad. Sci. USA 88, 26
      30], which results in extensive base-base stacking between the tandem G.A base
      pairs and their nearest neighbours. The terminal G.A base pairs are less stable
      than the central base pairs and show evidence of an equilibrium between two
      conformations, one involving BII phosphate.

PMID- 8143727
TI  - Heterogeneity of the rat NADH-cytochrome-b5-reductase transcripts resulting from
      multiple alternative first exons.
AB  - In order to understand the mechanisms responsible for the generation of different
      isoforms (membrane-bound and soluble) of NADH-cytochrome b5 reductase, and the
      different clinical forms of recessive congenital methemoglobinemia due to the
      deficiency of this enzyme in humans (type I, without mental retardation; type II,
      with mental retardation), we have looked for mRNA heterogeneity in various rat
      tissues. We have found four types of mRNAs, each with a different first exon (1L,
      1R, 1X and 1Y), all of which were precisely spliced to join the common second
      exon. Our results are consistent with a 5'-->3' 'scanning' mechanism for splice
      site selection. The previously characterized 1L and 1R transcripts arise from the
      alternative use of either a ubiquitous promoter (Pr-L) or an erythroid-specific
      promoter (Pr-R). In addition, the X and Y RNA species are novel transcripts which
      are expressed ubiquitously and at a relatively low level. The first alternative
      exons 1X and 1Y are noncoding, such that the AUG codon present in the common
      second exon is functional, as it is in the R mRNA. Thus, the X and Y mRNAs are
      expected to be translated in vivo into a ubiquitous soluble enzyme. Consequently,
      the rat NADH-cytochrome-b5-reductase gene is expressed through the use of at
      least four different promoters, which are probably subjected to different forms
      of regulation. This model of gene expression in rat could be important in
      understanding the basis for the different types of the NADH-cytochrome-b5
      reductase enzyme and their deficiency in man.

PMID- 8143728
TI  - Escherichia coli elongation-factor-Tu mutants with decreased affinity for
      aminoacyl-tRNA.
AB  - The two evolutionary well-conserved histidine residues, His66 and His118, of
      Escherichia coli elongation factor Tu have been subjected to mutational analysis.
      The two histidines have each been replaced by alanines, denoted H66A and H118A,
      respectively. His118 has also been substituted by glutamate, H118E. The three
      mutants have been characterized with respect to thermostability, GTPase activity
      and affinity for aminoacylated tRNA. Most conspicuously, the tRNA affinity is
      reduced or almost abolished. k-1 for dissociation of the ternary complex
      increases by factors of 14, 40 and 48 for H66A, H118A and H118E, respectively,
      when compared to the wild type. The half-lives for the non-enzymic deacylation of
      aminoacylated tRNA in the ternary complex are 391, 107, 69, 54 and 61 min for
      wild type, H66A, H118A, H118E and free aminoacylated tRNA, respectively. The Kd
      is about 20-times higher for H66A compared to wild type. Our results strongly
      suggest that His66 and His118 play major roles in stabilization of the ternary
      complex.

PMID- 8143729
TI  - Threonyl-tRNA synthetase from yeast. Discrimination of 19 amino acids in
      aminoacylation of tRNA(Thr)-C-C-A and tRNA(Thr)-C-C-A(2'NH2).
AB  - For discrimination between threonine and 18 other naturally occurring non-cognate
      amino acids by the class II aminoacyl-tRNA synthetase specific for threonine,
      discrimination factors (D) have been determined from Kca and Km values. The
      lowest values were found for Cys, Met, Val (D = 70-280), indicating that
      threonine is only 70-280-times more often esterified to tRNA(Thr)-C-C-A than are
      these non-cognate compounds at the same amino acid concentrations. The highest D
      values have been observed for Gly, Pro, Gln, Leu, Phe, and Lys (D = 1000-2000),
      for the other non-cognate amino acids D values are in the medium range 300-1000.
      Generally, threonyl-tRNA synthetase is less specific than the class I enzymes
      specific for Ile, Val, Tyr, Arg, but more specific than the only investigated
      class II enzyme specific for Lys. In aminoacylation of tRNA(Thr)-C-C-A(2'NH2)
      discrimination factors D1 are in the range 2-170. From D1 values and AMP
      formation stoichiometry, pre-transfer proof-reading factors II1, were determined;
      post-transfer proof-reading factors II2 were determined from D values and AMP
      formation stoichiometry in acylation of tRNA(Thr)-C-C-A. II1 values are in the
      range 1.8-33, II2 values in the range 1.4-22, thus threonyl-tRNA synthetase shows
      the highest post-transfer proof-reading activity of six investigated synthetases
      (specific for Ile, Val, Tyr, Arg, Lys). Initial discrimination factors caused by
      differences in Gibbs free energies of binding between threonine and non-cognate
      amino acids have been calculated from discrimination and proof-reading factors.
      Assuming a two-step binding process, two factors (I1 and I2) have been determined
      which can be related to hydrophobic interaction forces depending on accessible
      surface areas of the amino acids. The threonine side chain must be bound by
      hydrophobic forces and two hydrogen bonds. In contrast to proof-reading factors
      obtained with the synthetases specific for Ile, Val, Tyr, Arg, and Lys, proof
      reading factors II1 and II2 obtained with threonyl-tRNA synthetase are also
      related to hydrophobic interaction of the amino acid side chains and the enzyme.
      Threonyl-tRNA synthetase examines side chain structures of amino acids in the
      four postulated recognition steps, for each step the enzyme uses special distinct
      structures or conformations of the binding cleft.

PMID- 8143730
TI  - The nuclear-magnetic-resonance solution structure of the mutant alpha-amylase
      inhibitor [R19L] Tendamistat and comparison with wild-type Tendamistat.
AB  - The recombinant mutant alpha-amylase inhibitor [R19L]Tendamistat, with Arg19
      replaced by Leu, was prepared and its NMR solution structure determined. Based on
      complete sequence-specific 1H-NMR assignments, 845 nuclear Overhauser effect
      upper-distance constraints and 156 dihedral angle constraints were collected
      using two-dimensional homonuclear 1H-NMR experiments. The structure was
      calculated with the program DIANA, using the redundant dihedral angle constraints
      strategy for improved convergence. For restrained energy minimization, the
      programs FANTOM and AMBER were used. The wild-type NMR solution structure was
      similarly recalculated from the previously published input of conformational
      constraints [Kline, A., Braun, W. & Wuthrich, K. (1988) J. Mol. Biol. 204, 675
      724]. For each protein a group of 20 conformers represents a well-defined
      solution structure, with average root-mean-square-distance values for the
      backbone atoms of the individual conformers relative to the mean coordinates of
      50 pm. The two structures are nearly identical to each other and to the
      previously published Tendamistat structures in solution and in crystals. The only
      significant difference is strictly localized near the single amino acid
      substitution in the presumed active site -Trp18-Arg(Leu)-Tyr-, i.e. Leu19 and
      Tyr20 are more precisely defined in the solution structure of [R19L]Tendamistat
      than the corresponding residues Arg19 and Tyr20 in wild-type Tendamistat.

PMID- 8143731
TI  - Human tumor necrosis factor mutants with preferential binding to and activity on
      either the R55 or R75 receptor.
AB  - Previously, we reported that the cytotoxic activity of human (h) tumor necrosis
      factor (TNF) on murine (m) L929 cells requires the integrity of three loops
      (positions 30-36, 84-88 and 138-150) which cluster around the interface between
      each two subunits of the trimeric hTNF structure. The collection of hTNF mutants
      was further characterized by their activity on various human cell systems as well
      as by their binding to the two types of hTNF receptor (R), R55 and R75. It turned
      out that two amino acids (Leu29 and Arg32) were specifically involved in hR75
      binding, as Leu29-->Ser (L29S) and Arg32-->Trp (R32W) mutant molecules had
      largely lost binding to hR75, but not to hR55. In order to screen for more highly
      R55-specific mutants, nine other amino acids were inserted at these two
      positions; only the substitutions L29G and L29Y showed an increased differential
      binding as compared to L29S, while no further improvement was found with
      mutations at position 32 compared to R32W. Biological assays mediated either by
      hR55 or hR75 confirmed the results obtained by physical binding to purified
      receptors. A similar substitution in mTNF, Arg32-->Tyr, also resulted in a
      preferential loss of binding to hR75 and a large decrease in mR75-mediated
      bioactivity. Except for the double mutant L29S-R32W, all other tested amino acid
      substitutions in the loops at positions 30-36 or 84-88 of hTNF led to a
      substantial loss of affinity for both receptors and a concomitant reduction of
      biological activity. In the loop at positions 138-150, the non-conservative
      replacement of Glu by Lys at position 146 (E146K) resulted in an even lower
      binding to R75 as compared to R32W, while binding on and bioactivity through R55
      was only slightly reduced. Remarkably, a reversed differential binding was
      observed after substitution at position 143 in hTNF; replacing Asp by non
      conservative residues such as Tyr, Phe or Asn resulted in a much larger decrease
      in binding to R55 than to R75. In conclusion, receptor-specific mutants such as
      R32W, E146K and D143N can be used to study the function either of R55 or R75 on
      different human cell types. In vivo, we presume that the R55-specific mutants
      will retain antitumor activity in the absence of R75-dependent, severe side
      effects.

PMID- 8143732
TI  - pH-induced structural changes in human serum apotransferrin. pKa values of
      histidine residues and N-terminal amino group determined by 1H-NMR spectroscopy.
AB  - The binding of apotransferrin (80 kDa) to the transferrin receptor is known to be
      highly pH-dependent. We have investigated pH-induced structural changes in human
      serum apotransferrin over the pH* (meter reading in D2O solutions) range 2.5-11
      using 1H-NMR spectroscopy. The pKa values of 14 (possibly 15) of the 19 His
      residues in the protein have been determined as well as that of the terminal
      amino group (Val1, 7.75). About eight His residues deprotonate when the pH* is
      raised from the endosomal value of about 5.5 to the blood plasma value (7.4).
      Four His residues have pKa < 6. Sharp discontinuities in the His titration curves
      were observed below pH 4.3 and at pH 3.5 molten globule states were detected.

PMID- 8143733
TI  - Purification and partial characterization of a putative thymidylate synthase from
      Methanobacterium thermoautotrophicum.
AB  - A protein catalyzing the tritium exchange of [5-3H]deoxyuridine monophosphate ([5
      3H]dUMP) for solvent protons and the dehalogenation of 5-bromo-deoxyuridine
      monophosphate (Br-dUMP) has been isolated from the methanogenic archaea
      Methanobacterium thermoautotrophicum. These two activities are well-established
      side reactions of thymidylate synthase and do not require cofactors. Sodium
      dodecylsulfate/polyacrylamide gel electrophoresis of the purified enzyme showed a
      single band with a molecular mass of 27 kDa. The suggested molecular mass of the
      native protein calculated from sedimentation equilibrium experiments was 33.5
      kDa, indicating that the enzyme is a monomer. The pH optima were 9.0 and 7.0 for
      the exchange reaction and the dehalogenation, respectively. The effects of
      temperature, salt, reducing agent and inhibitors were determined. The apparent Km
      for the tritium exchange from [5-3H]dUMP was 7 microM and for the dehalogenation
      of Br-dUMP was 14 microM. However, thus far, the conditions for dTMP synthesis
      from dUMP have not yet been established. Incubation of the enzyme with dUMP,
      tetrahydromethanopterin, a folate analog present in methanogens, and formaldehyde
      did not yield dTMP. The first 30 amino acids of the amino terminus have been
      sequenced. However, there is no similarity with any of the thymidylate synthases.
      Surprisingly, the protein from M. thermoautotrophicum appears to be related to
      chitin synthases from several organisms.

PMID- 8143734
TI  - In vivo and in vitro photoinhibition reactions generate similar degradation
      fragments of D1 and D2 photosystem-II reaction-centre proteins.
AB  - Isolation of photosystem-II reaction centres from pea leaves after
      photoinhibitory treatment at low temperature (0-1 degrees C) has provided
      evidence for the mechanism of degradation of the D1 protein in vivo. These
      isolated reaction centres did not appear to be spectrally distinct from
      preparations obtained from control leaves that had not been photoinhibited.
      Breakdown fragments of both the D1 and D2 proteins were, however, found in
      preparations isolated from photoinhibited leaves, and showed similarities with
      those detected when isolated reaction centres were exposed to acceptor-side
      photoinhibition. Analyses of the origin of D1 fragments indicated that the
      primary cleavage site of this protein was between transmembrane helices IV and V
      indicative of the acceptor-side mechanism for photoinhibition. The origins of
      other D1 protein fragments indicate that some donor-side photoinhibition may also
      have occurred in vivo under the conditions employed. We have shown that the
      spectral and functional integrating of the isolated photosystem II reaction
      centre complex is resistant to proteolytic cleavage by trypsin. Use of a more non
      specific protease (subtilisin), however, caused significant destabilisation of
      the special pair of chlorophylls constituting the primary electron donor, P680,
      with a consequential loss of functional activity. Thus, it is possible that
      specific cleavage of photosystem-II reaction-centre proteins may occur in vivo
      following photoinhibitory damage without a significant change in structural
      integrity, a conclusion supported by the finding that photodamaged and normal
      reaction centres were isolated together.

PMID- 8143735
TI  - Human beta 1,4 galactosyltransferase and alpha 2,6 sialyltransferase expressed in
      Saccharomyces cerevisiae are retained as active enzymes in the endoplasmic
      reticulum.
AB  - Biosynthesis and intracellular transport of recombinant human full-length beta
      1,4 galactosyltransferase (GT) and full-length alpha 2,6 sialyltransferase (ST)
      were investigated in Saccharomyces cerevisiae. Recently, enzymic activity of
      recombinant GT (rGT) in crude homogenates of S. cerevisiae could successfully be
      demonstrated [Krezdorn, C., Watzele, G., Kleene, R. B., Ivanov, S. X. & Berger,
      E. G. (1993) Eur. J. Biochem. 212, 113-120]. In the present work, we show that,
      in yeast strains transformed with plasmid pDPSIA containing the cDNA coding for
      human ST, rST enzymic activity using asialo-fetuin or N-acetyllactosamine as
      acceptor substrates could readily be detected. Analysis by 1H-NMR spectroscopy of
      the disaccharide product of rGT, as recently reported, and the trisaccharide
      product of rST demonstrated that only the expected glycosidic linkages were
      formed. Following mechanical disruption of yeast cells, both enzymes sedimented
      with a fraction enriched in membranes of the endoplasmic reticulum (ER) and were
      activated by Triton X-100 3-5-fold. rGT and rST could be immunoprecipitated from
      their [35S]Met-labelled transformed yeast extracts using polyclonal antibodies
      raised against fusion proteins consisting of beta-galactosidase-GT or beta
      galactosidase-ST, respectively, expressed in Escherichia coli. For rGT a single
      glycosylated form of apparent molecular mass 48 kDa was reported, but for rST two
      main bands corresponding to apparent molecular masses of 48 kDa and 44 kDa,
      respectively, were detected. Immunoprecipitation from either tunicamycin-treated
      [35S]Met-labelled transformed yeast cells or labelling with radio-active sugars
      both indicated that the 44-kDa form of rST was non-glycosylated and that the 48
      kDa form of rST was core N-glycosylated. In addition, core glycosylation of both
      recombinant enzymes demonstrated that they were competent for translocation
      across the ER membranes. However, the 44-kDa form of rST was converted to the 48
      kDa glycosylated form only slowly, suggesting a mechanism of posttranslational
      translocation. Absence of hyperglycosylation of rST and rGT in wild type and lack
      of the Golgi-specific man-alpha 1,6-man epitope suggest that the recombinant
      enzymes did not enter the yeast Golgi apparatus. These results indicated that
      both rGT and rST are retained as enzymically active enzymes in the ER of yeast
      and suggest a ribonucleoprotein-independent import of rST into the ER.

PMID- 8143736
TI  - The type-III Fc receptor from Streptococcus dysgalactiae is also an alpha 2
      macroglobulin receptor.
AB  - We have cloned and sequenced the gene for a type-III Fc receptor from a
      Streptococcus dysgalactiae strain isolated from bovine mastitis and report here
      the complete sequence of the gene. The 1992-nucleotides-long open reading frame
      codes for a protein of 664 amino acids with a predicted molecular mass of 72 kDa
      (including the signal peptide). The C-terminal part of the protein is very
      similar to other streptococcal type-III receptors but contains five homologous
      IgG-binding domains compared to two or three in earlier reported Fc receptors of
      this type. Upstream of the IgG-binding domains, there is a unique sequence
      containing short repeated motifs. Subcloning different parts of the gene and
      expressing them as maltose-binding fusion proteins revealed that the upstream
      part is mediating binding to the plasma proteinase inhibitor alpha 2
      macroglobulin after its complex formation with proteases. In contrast to earlier
      described type-III Fc receptors, this molecule does not bind human serum albumin.

PMID- 8143737
TI  - Mossbauer and magnetic susceptibility studies on iron(II) metallothionein from
      rabbit liver. Evidence for the existence of an unusual type of [M3(CysS)9]3-
      cluster.
AB  - The magnetic properties of the Fe(II)-binding sites in Fe(II)7-metallothionein
      (MT) have been studied using Mossbauer spectroscopy and magnetic-susceptibility
      measurements. In agreement our previous results, simulation of the Mossbauer
      spectra showed the presence of paramagnetic and diamagnetic subspectra in the
      ratio 3:4. By comparison with Mossbauer spectra of the inorganic adamantane-like
      (Et4N)2[Fe4(SEt)10] model compound, the diamagnetic component in Fe(II)7-MT has
      been assigned to a four-metal cluster in which there is antiferromagnetic
      coupling between the high-spin Fe(II) ions. It is suggested that the organization
      of this cluster is similar to that determined in the three-dimensional structure
      of the protein, containing diamagnetic Zn(II) and/or Cd(II) ions. From magnetic
      susceptibility studies, an average magnetic moment of approximately 8.5 microB
      was obtained for the three remaining bound Fe(II) ions, responsible for the
      paramagnetic component observed in the Mossbauer studies. This value is slightly
      lower than that for three completely uncoupled Fe(II) ions, suggesting the
      existence of a three-metal cluster within which there is weak exchange coupling
      between adjacent Fe(II) ions. The spin-Hamiltonian formalism including, besides
      zero-field and Zeeman interaction, also exchange interaction among the three
      Fe(II) ions in the three-metal cluster, H = -J12 (S1.S2)-J23 (S2.S3)-J13 (S1.S3),
      was applied to simulate both magnetic-Mossbauer and magnetic-susceptibility data.
      Reasonable fits were achieved only with values magnitude of J12 = magnitude of
      J23 = magnitude of J13 = magnitude of J < 1 cm-1. Such a situation could not be
      reconciled with the chair-like geometry of the [M3(CysS)9]3- cluster determined
      with paramagnetic metal ions, where significantly stronger coupling would be
      anticipated (magnitude of J = 50-70 cm-1). However, modest exchange-coupling
      properties have been reported for a number of crystallographically characterized
      trinuclear [Fe3(SR)3X6]3- clusters (X = Cl, Br; R = Phe, p-tolyl, 2,6-Me2C6H3)
      distinguished by the preferential formation of a planar Fe3(mu 2-SR)3 ring
      [Whitener, M. A., Bashkin, J. A., Hagen, K. S., Girerd, J.-J., Gamp, E.
      Edelstein, N. & Holm, R. H. (1986) J. Amer. Chem. Soc. 108, 5607-5620]. It is
      therefore more likely that a pseudo-planar geometry rather than a chair-like
      geometry is present in the Fe3 cluster of Fe(II)7-MT. This would represent the
      first example of structural differences on binding divalent metal ions to this
      protein.

PMID- 8143738
TI  - Isolation of transcription factor IIIC from Dictyostelium discoideum.
AB  - Transcription factor IIIC (TFIIIC) binds in a sequence-specific manner to RNA
      polymerase-III-transcribed genes (e.g. tRNA genes). It sequesters other
      transcription factors into the preformed complex, thereby activating
      transcription by RNA polymerase III. The Dictyostelium discoideum homologue of
      TFIIIC was highly purified by affinity chromatography based on its tDNA-binding
      activity. This TFIIIC homologue is a multicomponent factor (molecular mass 380
      kDa), which binds to the B-box element of the internal tRNA gene promoter without
      significant A-box interaction. Partially purified D. discoideum TFIIIC is able to
      functionally complement a human RNA polymerase III in vitro transcription system
      depleted of human TFIIIC. We provide evidence that partially purified D.
      discoideum TFIIIC interacts in vitro with gene-external B-box elements present
      down-stream of many D. discoideum tRNA genes.

PMID- 8143739
TI  - The I-CeuI endonuclease: purification and potential role in the evolution of
      Chlamydomonas group I introns.
AB  - During genetic crosses between the interfertile green algae Chlamydomonas
      eugametos and Chlamydomonas moewusii, the I-CeuI endonuclease encoded by the
      fifth group I intron (CeLSU.5) in the C. eugametos chloroplast large subunit rRNA
      gene mediates the mobility of this intron by introducing a double-strand break
      near the insertion site of the intron in the corresponding C. moewusii intronless
      allele. To characterize the biochemical properties of this endonuclease, we have
      purified I-CeuI and determined the optimal reaction conditions for cleavage. I
      CeuI activity is maximal at 50 degrees C, pH 10.0, 2.5 mM MgCl2 and in the
      absence of NaCl. Unlike the well-characterized I-SceI endonuclease, I-CeuI
      remains stable following preincubation in the absence of substrate. We discuss
      the role that homing endonucleases may have played in the evolution of
      Chlamydomonas chloroplast group I introns.

PMID- 8143740
TI  - Possible kinetic mechanism of human placental alkaline phosphatase in vivo as
      implemented in reverse micelles.
AB  - Human placental alkaline phosphatase is an integral membrane protein. It
      catalyzes the hydrolysis of phosphoester linkage of a broad-range substrate. We
      have embedded the enzyme in a reverse micellar system prepared by dissolving the
      surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane. Linear
      Lineweaver-Burk and Eadie-Hofstee plots for the substrate and linear Arrhenius
      plot for the temperature-dependent enzyme reaction were obtained in reverse
      micelles suggesting that the substrate diffusion limitation was not a rate
      limiting step in the system and exchange of materials between reverse micelles
      was very rapid. The catalytic constant (kcat) of the enzyme was decreased, and
      the Km for the substrate was increased in reverse micelles, both in an
      exponential way with the [H2O]/ AOT] ratio (omega O). The enzyme was more stable
      in reverse micelles than in aqueous solution at 30 degrees C but was unstable at
      higher temperature (65 degrees C). The activation energy of the enzyme in reverse
      micelles was 46.5 +/- 2.6 kJ/mol, which was about 20 kJ/mol higher than that in
      aqueous solution and reflected in the lower Kcat value at low omega O. The
      binding affinity between the substrate 4-nitrophenyl phosphate and the enzyme in
      reverse micelles was decreased as implemented by the higher Km and higher Ki for
      phosphate values. In aqueous solution, the log kcat/pH plot suggested that amino
      acid residues with pKa values of 9.03 +/- 0.03 and 11.37 +/- 0.10 are involved in
      catalysis. The former should be deprotonated and the latter should be protonated
      for the reaction to proceed. In reverse micelles, both the above-mentioned pKa
      values were detected. However, both groups have to deprotonated to give the
      optimum catalytic function. In aqueous solution, the enzyme's specificity was
      highly dependent on pH and buffer. The pKa value of the amino acid residues
      involved in substrate binding was found to be 8.69 +/- 0.07 in carbonate buffer,
      but changed to 9.80 +/- 0.06 in Tris buffer. Our results suggested that the rate
      limiting step of the enzyme-catalyzed reaction may be changed from phosphate
      releasing in aqueous solution to another critical step in the reverse micelles.

PMID- 8143741
TI  - Direct analysis and significance of cardiolipin transverse distribution in
      mitochondrial inner membranes.
AB  - The distribution of cardiolipin across the inner mitochondrial membrane was
      directly determined by using the ability of the fluorescent dye 10-N-nonyl-3,6
      bis(dimethylamino)acridine (10-N-nonyl acridine orange) to form dimers when it
      interacts with the diacidic phospholipid. Two independent methods were employed:
      (a) a spectrophotometric measurement of 10-N-nonyl acridine orange binding to
      isolated rat liver mitochondria, mitoplasts and inside-out submitochondrial
      particles, and (b) a flow-cytometric analysis of specific red fluorescence,
      emitted when two dye molecules are bound to one membrane cardiolipin; the
      stoichiometry of 10-N-nonyl acridine orange binding to phosphatidylserine and
      phosphatidylinositol, 1 mol dye/mol phospholipid, prevented dye dimerisation and
      subsequent red-fluorescence appearance. 57% total cardiolipin was present in the
      outer leaflets of inner membranes of isolated organelles, a distribution
      confirmed by saturation measurements for mitoplasts and inside-out
      submitochondrial particles. The same asymmetry was directly observed in situ with
      mitochondrial membranes of quiescent L1210 cells, and with mitochondrial
      membranes of respiring yeasts. Nevertheless, alterations in ATP synthesis and
      inhibition of mitochondrial protein synthesis revealed that cardiolipin
      distribution was apparently tightly correlated with mitochondrial membrane
      assembly and activity.

PMID- 8143742
TI  - Structural analysis of the functional gene and pseudogene encoding the murine
      granulocyte colony-stimulating-factor receptor.
AB  - Granulocyte colony-stimulating factor is a cytokine which specifically regulates
      the production of neutrophilic granulocytes. The granulocyte colony-stimulating
      factor receptor (GCSFR) is mainly expressed in neutrophils and their precursor
      cells. In this study, we isolated the chromosomal gene for murine GCSFR and
      determined its structure. Like the human GCSFR gene homolog, it consists of 17
      exons. The exon-intron organization of the murine and human GCSFR-encoding genes
      are very similar, except that exon 14 and exon 15 in the murine gene are
      interrupted by a larger intron (greater than 10 kbp) than that found in the human
      gene (128 bp). This GCSFR-encoding functional gene (Csfgr) was localized to the
      distal region of murine chromosome 4 by interspecific backcross mapping. A
      comparison of the 5' flanking sequence of murine and human Csfgr revealed that a
      sequence of approximately 300 bp upstream from the cap site is highly conserved.
      Within this region, an 18-nucleotide element conserved in the promoter of the
      genes for neutrophil-specific enzymes, was found approximately 140 bp upstream
      from the cap site, suggesting an involvement of this element in the specific
      expression of GCSFR in neutrophilic granulocytes. In addition to the functional
      GCSFR-encoding gene, we isolated a pseudogene for GCSFR, which is flanked by a 15
      bp direct repeat at the 5' and 3' ends, and lacks all introns, exons 1-3 and
      exons 7-8 of the functional gene. The processed pseudogene has, in its most 5'
      region, a sequence of approximately 200 bp that is highly related to the DNA
      sequence approximately 1.2 kbp upstream of the cap site of the functional gene.

PMID- 8143743
TI  - Translocation and processing of various human parathyroid hormone peptides in
      Escherichia coli are differentially affected by protein-A-signal-sequence
      mutations.
AB  - Two staphylococcal protein-A signal sequences were constructed and tested for
      function in Escherichia coli, after being linked to human parathyroid hormone
      (hPTH) cDNAS representing the intact form (1-84 amino acids) and two N-terminal
      (1-37 and 1-7 amino acids) peptides. One signal sequence was identical to the
      wild type, and the other signal contained a deletion of 12 bp at the 3' end. The
      truncated hPTH cDNAs were fused at their 3' ends to IgG-binding domains (ZZ)
      derived from protein A in order to facilitate purification and characterization.
      The expression plasmid pSPTH, containing the wild-type signal sequence, secreted
      efficiently the intact recombinant hPTH (1-84) into the medium. Plasmids
      containing the truncated hPTH genes after the wild-type signal, gave rise to hPTH
      ZZ hybrid proteins which were correctly processed at the N-terminal, but the
      major fractions appeared in the periplasmic compartment. In contrast, the plasmid
      pS'PTH which harboured the 4-amino-acid signal deletion did not promote a uniform
      secretion of intact hPTH (1-84) to the medium, but released a non-processed form
      both into the periplasmic compartment and to the medium. The related plasmids
      pS'PTH37ZZ and pS'PTH7ZZ with the mutated signal sequence gave rise to small or
      trace amounts of unprocessed forms of fusion proteins in the medium and
      periplasm, thus the secretion competence was markedly reduced. Thus, for correct
      N-terminal processing, we conclude that the amino acid sequence in the signal
      adjacent to the expressed protein, is a key determinant. However, release into
      the medium or periplasmic space appeared to be dependent also on protein folding,
      irrespective of signal-sequence cleavage. Furthermore, we observed that the
      peptides with the wild-type signal sequence and correct N-terminal processing,
      were the only forms that showed internal cleavage of hPTH. Uncleaved signals may
      contribute to folding characteristics of the ensuing protein and e.g., prevent
      internal proteolysis.

PMID- 8143744
TI  - Molecular cloning and sequence analysis of the gene of the molybdenum-containing
      aldehyde oxido-reductase of Desulfovibrio gigas. The deduced amino acid sequence
      shows similarity to xanthine dehydrogenase.
AB  - In this report, we describe the isolation of a 4020-bp genomic PstI fragment of
      Desulfovibrio gigas harboring the aldehyde oxido-reductase gene. The aldehyde
      oxido-reductase gene spans 2718 bp of genomic DNA and codes for a protein with
      906 residues. The protein sequence shows an average 52% (+/- 1.5%) similarity to
      xanthine dehydrogenase from different organisms. The codon usage of the aldehyde
      oxidoreductase is almost identical to a calculated codon usage of the
      Desulfovibrio bacteria.

PMID- 8143745
TI  - Comparative studies on the primary structures and inhibitory properties of
      subtilisin-trypsin inhibitors from Streptomyces.
AB  - Three novel proteinaceous inhibitors of serine proteases which had been
      identified as Streptomyces subtilisin inhibitor-like (SIL) inhibitors were
      isolated from culture supernatant of Streptomyces; SIL2 from Streptomyces
      parvulus, SIL3 from Streptomyces coelicolor and SIL4 from Streptomyces
      lavendulae. They exhibited not only strong inhibitory activity toward subtilisin
      BPN' but also less strong inhibition of trypsin. Their primary sequences were
      determined by sequence analysis of peptides obtained by specific cleavage at the
      reactive site and subsequent proteolytic digestion. Each inhibitor consisted of
      about 110 amino acids, and was considered to form a dimer. The reactive site of
      the inhibitors was identified as Arg-Glu for SIL2 and SIL3, and Lys-Leu for SIL4,
      from sequence analysis of modified forms of the inhibitors produced from the
      inhibitor-subtilisin complex under acidic conditions. The presence of an
      arginine/lysine residue at the P1 site was in agreement with their trypsin
      inhibition property. Sequence comparison with other members of the Streptomyces
      subtilisin inhibitor family revealed that amino acid replacements in the three
      isolated SIL inhibitors were frequently localized on the surface region, and many
      of the amino acid residues in beta-sheets and the hydrophobic core were highly
      conserved. Values of the inhibitor constant (Ki) toward subtilisin BPN' and
      trypsin were also measured, and the differences were discussed on the basis of
      the determined structures of the inhibitors.

PMID- 8143746
TI  - Characterization of a membrane glycoprotein having pharmacological and
      biochemical properties of an AT2 angiotensin II receptor from human myometrium.
AB  - The angiotensin II receptors of human myometrial tissue were characterized using
      ligand binding, cross-linking with radioactive label, detergent solubilization
      and partial purification by lectin-affinity chromatography. Human myometrial
      membrane preparations contained variable amount (5-650 fmol/mg protein) of high
      affinity (Kd = 44-65 pM) binding sites for 125I-CGP42112, a ligand specific for
      the AT2 subtype of angiotensin II receptors. Competition studies with AT1
      specific and AT2-specific compounds indicated that angiotensin II receptors on
      these membranes were exclusively of the AT2 subtype. The binding sites for 125I
      CGP42112 were efficiently solubilized by the detergent Chaps, albeit with a
      marked decrease in affinity (Kd = 1.2 nM). The proteins in the myometrial
      membrane preparation were cross-linked to 125I-[Sar1, Ile8]angiotensin II
      (Sarile) with disuccinimidyl suberate. When low concentrations of cross-linker
      were used, a single radiolabelled band of about 66-70 kDa was revealed on
      SDS/PAGE. At higher concentrations additional bands of about 105-120 kDa and 200
      kDa were labelled. The 66-70-kDa and 105-120-kDa bands were separated by
      electroelution of SDS/PAGE gel slices and submitted to trypsin cleavage. The
      tryptic-peptide maps were identical for both products, suggesting that the
      additional bands are homodimers and trimers of the labelled polypeptide. The
      Chaps-solubilized receptor was retained on wheat-germ-agglutinin-Sepharose and
      specifically eluted by the competing sugar triacetylchitotriose, leading to a
      fivefold purification factor. Treatment of the 125I-Sarile-labelled protein with
      N-glycanase caused a shift in its apparent molecular mass on SDS/PAGE from 66-70
      kDa to 33 kDa.

PMID- 8143747
TI  - Characterisation and mode of in vitro replication of pea chloroplast OriA
      sequences.
AB  - A partially purified replicative system of pea chloroplast that replicates
      recombinant DNAs containing pea chloroplast origin sequences has been
      characterised. Polymerisation by this system is very fast and insensitive to
      chain terminators like dideoxynucleotides, arabinosylcytosine 5'-triphosphate,
      etc. Both strands of template DNA are synthesized and single-stranded DNA
      templates undergo more than one round of replication. When sequences of either of
      the two chloroplast origins of replication (OriA or OriB) are used as templates,
      the replicative intermediates are found to have sigma structures. Electron
      microscopic analysis of the sigma structures restricted with various enzymes
      reveals that the initiation site of in vitro replication maps near the
      displacement-loop regions where replication initiates also in vivo. Although the
      observed replication initiation in the OriA recombinant template is chloroplast
      DNA-specific, the mode of replication is different from that observed in vivo
      with intact ctDNA. However, when the template DNA contains both the OriA and OriB
      sequences, the in vitro replication proceeds in the theta mode, the mode of
      replication usually observed in vivo.

PMID- 8143748
TI  - Purification of 1,3-beta-D-glucan synthase activity from pea tissue. Two
      polypeptides of 55 kDa and 70 kDa copurify with enzyme activity.
AB  - From pea plasma membranes isolated by aqueous polymer two-phase partitioning we
      have purified 1,3-beta-D-glucan synthase [glucan synthase-II (GS-II) or callose
      synthase], an enzyme that several reports have suggested consists of between six
      and nine different subunits. The procedure involves (a) preliminary removal of
      peripheral proteins by 0.1% digitonin; (b) solubilization of GS-II with 0.5%
      digitonin; (c) precipitation of activity-irrelevant proteins from the digitonin
      extract by Ca2+, spermine and cellobiose, which are GS-II effectors needed in
      step (d); (d) product entrapment by formation of 1,3-beta-D-glucan from UDP-Glc
      by GS-II in the presence of the mentioned effectors, followed by centrifugal
      sedimentation of product micelles and elution of proteins therefrom with buffer;
      (e) preparative isoelectric focusing (IEF) of product-entrapped proteins; and (f)
      glycerol gradient centrifugation of the fractions of peak GS-II activity from
      IEF. The procedure yields 300-fold enrichment of GS-II specific activity over
      that in isolated plasma membranes, and 5500-fold over that in the original
      homogenate. Out of approximately six principal polypeptides that occur after the
      product entrapment step, the glycerol gradient GS-II activity peak contains only
      two major polypeptides, one of 55 kDa and another of 70 kDa, plus minor amounts
      of one or two others whose distribution and occurrence indicate are not
      responsible for GS-II activity. Antisera against either the 55-kDa or the 70-kDa
      polypeptide adsorb more than 60% of the GS-II activity from a product-entrapped
      preparation. After native gel electrophoresis, GS-II activity is associated with
      a single protein band of very large molecular mass, whose principal components
      are the 55-kDa and 70-kDa polypeptides, accompanied by minor amounts of a few
      other polypeptides most of which do not occur in enzyme preparations purified by
      the previously described procedure. The 55-kDa but not the 70-kDa component can
      be labeled by ultraviolet irradiation of the plasma membranes in the presence of
      [alpha-32P]UDP-Glc under GS-II assay conditions. It seems likely, therefore, that
      the 55-kDa and 70-kDa polypeptides form a large catalytic complex of which the 55
      kDa component is the UDP-Glc-binding subunit.

PMID- 8143749
TI  - Coordination of catalytic activities within enzyme complexes.
AB  - If two enzymes are physically and permanently associated as a bi-enzyme complex
      and if these enzymes catalyze non-consecutive chemical reactions, either of these
      reactions may inhibit or activate the other. If these reactions belong to two
      different metabolic cycles, the functioning of one of these cycles will control
      the fine tuning of the other. Thus simple kinetic considerations lead to the
      conclusion that, owing to the spatial organization of enzymes as multimolecular
      complexes, a fine tuning and a coordination of different metabolic networks, or
      cycles, may be exerted. It thus appears that channelling of reaction
      intermediates within a multienzyme complex does not represent the only functional
      advantage brought about by this type of spatial molecular organization.

PMID- 8143750
TI  - Activation of the retinal cGMP-specific phosphodiesterase by the GDP-loaded alpha
      subunit of transducin.
AB  - The interaction of the GDP-bound form of the alpha-subunit of transducin (T alpha
      GDP) with the cGMP-specific phosphodiesterase, the effector enzyme in the visual
      system, has been studied. T alpha GDP is demonstrated to be able to activate the
      phosphodiesterase: (a) the basal activity in suspensions of dark-adapted retinal
      rod outer segments, examined in the absence of GTP, was found to be inhibited by
      binding of transducin to activated rhodopsin (Rh*) and by the complex of the beta
      and gamma-subunits of transducin (T beta gamma); (b) purified T alpha GDP is
      able to activate phosphodiesterase in the presence of membranes; (c) no
      activation is obtained either with holotransducin (T alpha GDP T beta gamma) or
      with T alpha GDP in the presence of excess T beta gamma to prevent dissociation
      of TGDP. The maximal level of phosphodiesterase activation reached with T alpha
      GDP (about 1500 mol cGMP/mol phosphodiesterase-1.s-1) is similar to that obtained
      through the 'classical' activation by T alpha GTP whereas the apparent affinity
      of T alpha GDP for phosphodiesterase (Kd about 50 microM) is much lower than that
      of T alpha GTP. Our data suggest that GTP hydrolysis itself does not inactivate T
      alpha. The role of T beta gamma to sequester T alpha is therefore of critical
      importance for phosphodiesterase inactivation. Our results support observations
      on the regulation of adenylyl cyclase by G-proteins, which suggested the ability
      of the free alpha-subunits loaded with GDP to activate their effectors.

PMID- 8143751
TI  - Protein stabilization by hydrophobic interactions at the surface.
AB  - The contribution of the solvent-exposed residue 63 to thermal stability of the
      thermolysin-like neutral protease of Bacillus stearothermophilus was studied by
      analyzing the effect of twelve different amino acid substitutions at this
      position. The thermal stability of the enzyme was increased considerably by
      introducing Arg, Lys or bulky hydrophobic amino acids. In general, the effects of
      the mutations showed that hydrophobic contacts in this surface-located region of
      the protein are a major determinant of thermal stability. This observation
      contrasts with general concepts concerning the contribution of surface-located
      residues and surface hydrophobicity to protein stability and indicates new ways
      for protein stabilization by site-directed mutagenesis.

PMID- 8143752
TI  - Primary sequence, oxidation-reduction potentials and tertiary-structure
      prediction of Desulfovibrio desulfuricans ATCC 27774 flavodoxin.
AB  - Flavodoxin was isolated and purified from Desulfovibrio desulfuricans ATCC 27774,
      a sulfate-reducing organism that can also utilize nitrate as an alternative
      electron acceptor. Mid-point oxidation-reduction potentials of this flavodoxin
      were determined by ultraviolet/visible and EPR methods coupled to potentiometric
      measurements and their pH dependence studied in detail. The redox potential E2,
      for the couple oxidized/semiquinone forms at pH 6.7 and 25 degrees C is -40 mV,
      while the value for the semiquinone/hydroquinone forms (E1), at the same pH, -387
      mV. E2 varies linearly with pH, while E1 is independent of pH at high values.
      However, at low pH (< 7.0), this value is less negative, compatible with a redox
      linked protonation of the flavodoxin hydroquinone. A comparative study is
      presented for Desulfovibrio salexigens NCIB 8403 flavodoxin [Moura, I., Moura,
      J.J.G., Bruschi, M. & LeGall, J. (1980) Biochim. Biophys. Acta 591, 1-8]. The
      complete primary amino acid sequence was obtained by automated Edman degradation
      from peptides obtained by chemical and enzymic procedures. The amino acid
      sequence was confirmed by FAB/MS. Using the previously determined tridimensional
      structure of Desulfovibrio vulgaris flavodoxin as a model [similarity, 48.6%;
      Watenpaugh, K.D., Sieker, L.C., Jensen, L.H., LeGall, J. & Dubourdieu M. (1972)
      Proc. Natl Acad. Sci. USA 69, 3185-3188], the tridimensional structure of D.
      desulfuricans ATCC 27774 flavodoxin was predicted using AMBER force-field
      calculations.

PMID- 8143754
TI  - A new method for the determination of the cytotoxicity of bile acids and aqueous
      phase of stool: the effect of calcium.
AB  - Soluble secondary bile acids in the colon are supposed to be cytotoxic for normal
      colonic cells, resulting in an increased compensatory proliferation of colonic
      crypt cells, which is associated with an increased risk for colonic cancer. We
      developed a sensitive method to determine cytotoxicity of bile acids in the HT-29
      colon cancer cell line, using a tetrazolium-based colorimetric assay. Only in
      vital cells, tetrazolium-salts are converted into formazan, which can be measured
      easily. Chenodeoxycholic acid and deoxycholic acid (DCA) were cytotoxic in
      concentrations above 100 microM, which is in the physiological range for soluble
      DCA in faeces. Conjugation of bile acids diminished cytotoxicity 7-10 fold. In
      this concentration range, no effect of calcium or calcium phosphate was
      demonstrated, suggesting that the effect of calcium on colonic proliferation is
      not mediated by a precipitation of soluble bile acids in the large bowel.
      Finally, we could demonstrate a significant correlation between the cytotoxicity
      of the aqueous phase of faeces and the soluble DCA concentration.

PMID- 8143753
TI  - Analysis of genes encoding highly conserved lysine-rich proteins in Aplysia
      californica and Saccharomyces cerevisiae.
AB  - To isolate a gene that can be used as an internal control in studies on gene
      expression in Aplysia californica neurons, we have characterized a cDNA clone
      (pKRP-A) isolated on the basis of its high expression in A. californica neurons.
      This cDNA is of 850 nucleotides and codes for a putative 29-kDa lysine-rich
      protein. Blotting experiments revealed that the gene is expressed in all tested
      A. californica tissues, and in individually identified neurons of the abdominal
      ganglion, suggesting that this gene can be efficiently used as internal control
      in studies of gene expression. We have also isolated one cDNA and two different
      genomic clones from yeast libraries that show 59% identity with pKRP-A. Sequence
      comparison of genomic clones, as well as PCR and Southern blotting experiments,
      revealed that at least two homologous genes are present in yeast. Northern
      blotting experiments revealed that the expression of the gene is strongly
      repressed at 39 degrees C.

PMID- 8143755
TI  - Lymphatic clearance of synovial fluid in conscious pigs: the aminoterminal
      propeptide of type III procollagen.
AB  - The aminoterminal propeptide of type III procollagen (PIIINP) in serum is
      employed as a direct marker of fibrillogenesis. The balance between local
      fibrillogenesis and serum PIIINP is governed by the transport and possible
      degradation en route from tissue to circulation. In conscious pigs, we
      investigated the transport of PIIINP from the knee cavity into the circulation
      after intra-articular injection of radiolabelled PIIINP followed by sequential
      sampling of thoracic duct lymph, serum and urine. Clearance from the joint space
      was evaluated by external detection of 131I-HSA, used as co-tracer. Lymph samples
      were gel filtrated to assess possible lymphatic degradation of the intact PIIINP.
      125I-PIIINP and 131I-HSA were found in thoracic duct lymph within 20 min of the
      intra-articular injection. Both isotopes had a biphasic appearance, with the
      first peak after 60 min and a larger peak after 150 min. During the 6 h
      observational period 18% of the injected PIIINP was found in the lymph. Gel
      chromatography of lymph showed the fast formation of a small fraction with a
      lower MW than that of PIIINP, which suggests that some degradation of PIIINP may
      occur through the lymphatics. The half-life of the joint clearance of HSA by bulk
      flow was assessed to be 8.3 h. The clearance of PIIINP from the joint was
      estimated to be equal to that of HSA, which indicates that PIIINP leaves the
      joint space by bulk flow as has been proposed for HSA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8143756
TI  - Ursodeoxycholic acid improves ethinyl estradiol-induced cholestasis in the rat.
AB  - The effect of oral chronic administration of ursodeoxycholic acid has been
      examined in rats with cholestasis induced by ethinyl estradiol. Ursodeoxycholic
      acid at the dose of 25 mg kg-1 per day during 4 days, did not improve the
      decrease in basal bile flow and bile acid secretion induced by ethinyl estradiol
      alone. In contrast, when ursodeoxycholic acid was given at the same dose during
      10 days, basal bile flow was significantly improved and basal bile acid secretion
      was restored to control values. When ursodeoxycholic acid was given at the dose
      of 500 mg kg-1 per day, basal bile flow and bile acid output were not further
      improved. However, bile flow and bile acid output under taurocholate infusion
      were restored to control values. Bile of rats treated with ursodeoxycholic acid
      was enriched with this bile acid. These results show a significant improvement of
      ethinyl estradiol-induced cholestasis in rats after chronic administration of
      ursodeoxycholic acid and support the use of this bile acid in intrahepatic
      cholestasis in man.

PMID- 8143757
TI  - Decreased sensitivity to adenosine in platelets from patients with familial
      hypercholesterolaemia--a change reversed by cholestyramine treatment.
AB  - Platelet-rich plasma was obtained from patients with untreated heterozygous
      familial hypercholesterolaemia (FH), from FH patients treated with cholestyramine
      and from control subjects. Responsiveness of platelets to the aggregation
      inhibitors adenosine, its analogue N-ethylcarboxamidoadenosine (NECA) and
      prostaglandin I2 was decreased in FH. Patients on cholestyramine therapy showed
      normal responsiveness to adenosine and NECA. There were only minor changes in the
      binding of [3H]NECA to high-affinity binding sites on platelet membranes from
      untreated FH or cholestyramine-treated FH patients. The initial rate of cyclic
      AMP formation in response to a high concentration of NECA was severely decreased
      in platelets from FH patients. By contrast, the rate of cyclic AMP formation in
      response to forskolin or a high concentration of prostaglandin I2 was unchanged.
      These data point to a defect in the coupling of the platelet A2 adenosine
      receptor to adenylyl cyclase in untreated FH patients.

PMID- 8143759
TI  - Comparison of intestinal absorption of cholesterol with different plant sterols
      in man.
AB  - Intestinal absorption of cholesterol, campesterol, campestanol, stigmasterol and
      sitosterol were measured in 10 healthy subjects by an intestinal perfusion
      technique over a 50 cm segment of the upper jejunum using sitostanol as non
      absorbable marker. Cholesterol absorption was highest and averaged 33%., whereas
      the absorption rate of sitosterol averaged 4.2% and of stigmasterol 4.8%. Higher
      absorption rates were found for campesterol (9.6%). Campestanol, the 5 alpha
      saturated derivative of campesterol, showed the highest absorption rate (12.5%)
      of all plant sterols. A positive correlation between the absorption rate of
      cholesterol and campesterol was established. In addition, there was a negative
      correlation between the ratio of sitosterol to cholesterol and the mass of
      cholesterol absorption. These results are in agreement with previous observations
      in animal studies, namely, that increasing the length of the side-chain of
      cholesterol decreases the absorbability of the sterol. Surprisingly, campestanol,
      the 5 alpha saturated derivate of campesterol, was shown to have higher
      absorbability compared with its unsaturated compound. This finding is in contrast
      to previous assumptions, that hydrogenisation of the nucleus double bond of a
      sterol causes a decrease of absorbability, as has been demonstrated for
      cholesterol/cholestanol and sitosterol/sitostanol.

PMID- 8143758
TI  - Changes in lipoprotein(a), LDL-cholesterol and apolipoprotein B in homozygous
      familial hypercholesterolaemic patients treated with dextran sulfate LDL
      apheresis.
AB  - We evaluated the effect of periodical treatment with LDL-apheresis by adsorption
      to dextran sulfate (Liposorber LA-15) on several aspects related to LDL and
      Lipoprotein(a) metabolisms, in three homozygous familial hypercholesterolaemic
      patients with LDL receptor deficiency. The dextran sulfate columns retained
      apolipoprotein B-containing particles with high affinity and capacity, in such a
      way that the treatment of a volume of plasma equivalent to three times the
      patient plasma volume resulted in an 85% decrease of circulating LDL-cholesterol
      and Lipoprotein(a). The continuous treatment with LDL-apheresis was highly
      beneficial for these patients since an average plasma concentration lower than
      200 mg dl-1 for LDL-cholesterol, and lower than 25 mg dl-1 for Lipoprotein(a)
      could be achieved by treating the patients once a week. After each apheresis
      treatment, plasma concentrations of these metabolites progressively returned to
      the pretreatment, steady-state, levels. The analysis of the rates of return
      allowed us to estimate the fractional catabolic rates. FCRs of LDL-cholesterol
      were 0.052, 0.049 and 0.047 pools day-1, and those of apolipoprotein B, 0.065,
      0.045 and 0.050 pools day-1 in the three subjects, respectively. These values are
      much lower than those in normolipidaemic individuals as observed by others, and
      are in accordance with the LDL-receptor deficiency condition of our patients. Two
      of them had highly elevated Lipoprotein(a) plasma concentrations, and their FCRs
      of Lipoprotein(a) were calculated to be 0.112 and 0.066 pools day-1.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143760
TI  - Influence of insulin on glucose metabolism and lipolysis in adipose tissue in
      situ in patients with liver cirrhosis.
AB  - The influence of insulin on lipolysis and glucose metabolism in abdominal adipose
      tissue was studied in situ with the microdialysis technique during a euglycaemic
      insulin clamp (1 mU kg-1 min-1) in nine cirrhotic patients and 10 controls. The
      cirrhotic patients displayed a 50% decrease in glucose utilization rate during
      the clamp (P < 0.001). Dialysate glucose levels decreased similarly by 20-30%.,
      in patients and controls, which in the presence of unchanged local blood flow in
      the adipose tissue in response to insulin, is at hand with a glucose uptake into
      the adipocytes of similar magnitude in both groups. Before and during the clamp,
      the arterial and dialysate levels of glycerol were higher in the patients than in
      the control subjects (ANOVA P = 0.001 and 0.048 in arterial blood and dialysate,
      respectively). In relative terms, however, insulin induced a 70% reduction of
      arterial and dialysate glycerol in both groups. The concentrations of lactate and
      pyruvate in the dialysate and blood increased in a similar way in both groups
      during hyperinsulinaemia. The results suggest an increased rate of lipolysis in
      cirrhotic patients. Insulin cannot lower it to normal, although it is still
      capable of achieving a relative reduction. No explanation was found in the
      adipose tissue to the insulin resistance to whole-body glucose utilization that
      was noted in the patients with cirrhosis.

PMID- 8143761
TI  - The effects of hydrocortisone on in vitro lymphocyte proliferation and
      interleukin-2 and -4 production in corticosteroid sensitive and resistant
      subjects.
AB  - Corticosteroids (CS) are potent immunosuppressive and anti-inflammatory agents
      which are frequently used to treat a number of conditions such as rheumatoid
      arthritis (RA), asthma, and renal allograft rejection. Patients taking
      corticosteroids can be divided into 'steroid-sensitive' (SS) and 'resistant' (SR)
      groups on clinical and laboratory criteria. Corticosteroid 'resistance' has been
      extensively documented in asthma and renal allografting. The underlying
      mechanisms are unknown. Using the inhibition by hydrocortisone of concanavalin-A
      induced lymphocyte proliferation in vitro, we have divided rheumatoid arthritis
      patients (RA) and normal controls (HC) into SS and SR groups. The SS and SR
      phenotypes were stable over several months in RA and HC subjects. Inhibition of
      Con-A induced production of interleukin-2 and -4 by corticosteroids in vitro
      correlated with the in vitro defined SS and SR phenotype. When highly purified T
      cells were stimulated via the CD3 and CD28 receptor pathways, corticosteroids did
      not inhibit cell proliferation in SS and ST subjects. It may be concluded that
      the SS and SR phenomenon is a stable intrinsic property of the individual which
      is dependent primarily on the inhibitory effects of corticosteroids on accessory
      cell function and only secondarily on T-cell function. This is a novel
      observation for the inhibitory effects of corticosteroids on T-lymphocytes.

PMID- 8143762
TI  - CETP-catalysed transfer of cholesterylesters from HDL to apo B-containing
      lipoproteins in plasma from diabetic patients.

PMID- 8143763
TI  - Extracellular matrix components regulating glandular differentiation and the
      formation of basal lamina of a human pancreatic cancer cell line in vitro.
AB  - The interaction between the extracellular matrix and human tumor-cell clones S2
      013 and S2-020, derived from a pancreatic cancer cell line (SUIT-2), was examined
      in vitro, using various cell differentiation-promoting matrices in two- and three
      dimensional cultures. S2-013 cells (well-differentiated tubular adenocarcinoma in
      xenografts in nude mice) cultured in Matrigel formed glandular structures.
      Ultrastructural observation revealed a morphological polarity of cells and a
      distinct basal lamina. On the other hand, S2-020 cells (poorly differentiated
      tubular adenocarcinoma in xenografts) cultured in Matrigel formed neither
      glandular structures nor a basal lamina, but only cell aggregates. The morphology
      of these two sublines cultured in Matrigel expressed the histological degree of
      differentiation which they presented in nude mice. In contrast, in type I
      collagen gel, S2-013 cells formed glandular structures without a basal lamina,
      and in soft agar, they were able to form neither glandular structures nor a basal
      lamina. S2-020 cells cultured in type I collagen gel or soft agar formed the same
      simple cell aggregates as in Matrigel. Matrices used in a three-dimensional
      culture influenced the degree of differentiation in S2-013 cells but had no
      effect on the morphological differentiation in S2-020 cells. To detect the
      factors which induce basal lamina formation, S2-013 cells were cultured on a
      microporous membrane coated with extra-cellular matrix components such as
      laminin, type IV collagen, and fibronectin. S2-013 cells formed a basal lamina
      only on the laminin. These cell lines may be useful in investigating the
      mechanisms regulating the formation of glandular structures and basal lamina.

PMID- 8143764
TI  - Chemical induction of stress proteins does not induce splicing thermotolerance
      under conditions producing survival thermotolerance.
AB  - Cell survival during a severe heat stress can be enhanced when heat shock
      proteins are induced prior to the severe heat treatment. Induction can be
      accomplished either by heat or chemical treatments. The increase in survival at
      these severe elevated temperatures after pretreatment has been referred to as
      thermotolerance, which we now refer to as survival thermotolerance. It has also
      been shown previously that mild heat treatment allows splicing in cells subjected
      to a severe heat treatment, now referred to as splicing thermotolerance. The
      experiments shown here demonstrate that even though chemical induction of the
      heat shock proteins leads to survival thermotolerance, this same treatment does
      not induce splicing thermotolerance. These are the first results that demonstrate
      at least two distinct aspects of thermotolerance.

PMID- 8143765
TI  - Expression of growth arrest-specific (gas) genes in senescent murine cells.
AB  - The growth arrest-specific (gas) genes were initially identified on the basis of
      their preferential expression in mouse fibroblasts during quiescence, followed by
      down-regulation upon reentry into the cell cycle. We here report studies on the
      expression of these genes in murine fibroblasts undergoing replicative senescence
      in vitro. Our results indicate a different behavior between senescent and GO
      arrested quiescent fibroblasts. Expression of the gas1 and 6 genes was
      dramatically reduced in senescent cells. Only basal levels of gas2, 3, and 5
      genes were detected in senescent fibroblasts, and they were independent of the
      growing conditions of the cultures. Down-regulation of the gas1 gene expression
      in senescent cells was apparently due to reduced transcription of the gas1 gene.
      This correlates with an altered pattern of factors that bind to the promoter
      region of the gas1 gene, as measured by band shift assay with nuclear extracts of
      senescent fibroblasts.

PMID- 8143766
TI  - Characterization of the function of the NIN1 gene product of Saccharomyces
      cerevisiae.
AB  - The nin1-1 mutant has been isolated as a temperature-sensitive mutant whose
      nucleus arrested at G2 phase and eventually disintegrated upon temperature
      upshift. In this study, a genetic event occurring in the nin1-1 mutant was found
      to be a frameshift mutation, resulting in a truncated protein smaller than the
      wild-type Nin1 protein. We found new phenotypes associated with the nin1-1
      mutation: (i) rates of mitotic recombination and chromosome/plasmid loss in the
      nin1-1 strain were higher than those in the wild-type strain, and (ii) the mutant
      was more sensitive to UV irradiation than the wild-type strain. We found dotted
      structures in the cytoplasm of the wild-type cells by indirect immunofluorescence
      microscopy using the anti-Nin1 antibody. Similar results were obtained when we
      analyzed the localization of Nin1-beta-galactosidase fusion protein formed in the
      cells expressing the NIN-lacZ fusion gene, which is active as NIN1, with anti
      beta-galactosidase antibody. The subcellular fractionation method revealed that
      Nin1 protein was not localized in a particular fraction of the cell lysate.

PMID- 8143767
TI  - Constitutive activation of the collagenase promoter in recessive dystrophic
      epidermolysis bullosa fibroblasts: role of endogenously activated AP-1.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is a mutilating disease of the
      skin characterized by recurrent blistering and erosions that result from
      compromised integrity of the basement membrane zone. In this study, fibroblasts
      derived from the skin of RDEB patients were characterized for expression of the
      major metalloproteinases, particularly interstitial collagenase. Consistent with
      previous reports on increased collagenase protein levels in fibroblasts from some
      RDEB patients, we found that steady-state levels of collagenase mRNA were
      significantly increased in fibroblast strains derived from three of five RDEB
      patients compared to fibroblasts obtained from normal donors. Stromelysin mRNA
      was elevated in the same three fibroblast strains, whereas expression of neither
      the 72- nor the 92-kDa type IV collagenases was different from that of controls.
      Tissue inhibitor of metalloproteinases was expressed in RDEB fibroblasts at
      levels similar to those observed in normal fibroblasts. To investigate the
      mechanism behind the steady-state elevation in collagenase and stromelysin
      expression, AP-1 expression and activation were studied. Although levels of Jun
      expression were not different from those seen in normal fibroblasts, AP-1
      activity, as assessed by ability to bind to a TPA response element-containing
      oligonucleotide, was endogenously elevated in RDEB fibroblasts compared to normal
      fibroblasts. Transfection studies using a plasmid construct containing the
      collagenase promoter linked to a CAT reporter gene demonstrated that RDEB
      fibroblasts were able to support active transcription of the promoter compared to
      normal fibroblasts. These studies support the hypothesis that RDEB fibroblasts
      contain chronically activated AP-1, and perhaps other transactivating factors,
      that contribute to the cellular phenotype of collagenase and stromelysin
      overexpression.

PMID- 8143768
TI  - Cisplatin induces apoptosis in a human ovarian carcinoma cell line without
      concomitant internucleosomal degradation of DNA.
AB  - After treatment of the human ovarian carcinoma cell line, CH1, with cisplatin,
      cells detached from the culture dish in a time- and dose-dependent fashion. These
      cells showed morphological changes indicative of apoptosis. Their DNA had not
      been degraded into oligonucleosomal fragments, but the DNA had been cut into
      larger fragments (30 kbp) of a size associated with chromatin loops. We conclude
      that cisplatin killed these ovarian cells by inducing apoptosis. However, in
      these cells, apoptosis was not accompanied by internucleosomal degradation of
      DNA. Our data are consistent with the hypothesis that the introduction of a
      double-strand break at a specific site in the chromatin loops is an early event
      in apoptosis. This degradation is accompanied by morphologically observable
      changes in chromatin structure. Internucleosomal degradation, when it occurs, is
      a late event.

PMID- 8143769
TI  - Insulin-like growth factor I regulation of Swarm rat chondrosarcoma chondrocytes
      in culture.
AB  - Insulin-like growth factor I (IGF-I) is anabolic for chondrocytes and is thought
      to be important in regulating such normal cartilaginous tissues as the epiphyseal
      growth plate. In the present studies, we have investigated the role of IGF-I in
      the regulation of neoplastic cartilage. Chondrocytes cultured from a
      transplantable rat chondrosarcoma were analyzed for responsiveness to IGF-I with
      respect to DNA and glycosaminoglycan synthesis as determined by labeling with
      radioactive thymidine and sulfate, respectively. Stimulation of [3H]thymidine and
      [35S]sulfate incorporation by IGF-I was two to four times that in serum-free
      controls, with half-maximal stimulation at 1 x 10(-9) M. The efficacy of IGF-I
      was approximately one-half of that of serum in stimulating [3H]thymidine
      incorporation and was comparable to that of serum for [35S]sulfate incorporation.
      When Swarm rat chondrosarcoma chondrocytes were cultured in the presence of IGF-I
      and exposed to graded concentrations of anti-IGF-I antibody, [3H]thymidine
      incorporation and [35S]sulfate incorporation were attenuated in a dose-dependent
      fashion to 29 and 25% of antibody-free controls, respectively. Nonspecific
      antibody not raised against IGF-I was not inhibitory. These observations suggest
      that the majority of IGF-I action on these cells is susceptible to
      immunoinhibition. To estimate the contribution of IGF-I to the regulation of
      these cells by serum, Swarm rat chondrosarcoma chondrocytes were cultured with
      graded concentrations of either calf serum or fetal calf serum in the presence of
      anti-IGF-I antibody, nonspecific antibody, or no other additives. Specific
      antibody attenuated the effect of calf serum on both [3H]thymidine and
      [35S]sulfate incorporation with overall inhibition of 52% (P < 0.01) and 48% (P <
      0.001), respectively. Nonspecific antibody super-imposed small, variably
      stimulatory or inhibitory effects on those of calf serum. When chondrosarcoma
      chondrocytes were incubated with fetal calf serum, anti-IGF-I antibody exerted a
      minimal inhibitory effect, reducing both [3H]thymidine and [35S]sulfate
      incorporation by less than 25%. The immunoinhibition of both pre- and postnatal
      serum could be overcome in a dose-dependent fashion by increasing serum
      concentrations. These results suggest that the factors influencing Swarm rat
      chondrosarcoma chondrocytes may be developmentally regulated and that the
      contribution of IGF-I to the action of serum increases between fetal and post
      natal life. These data support the hypothesis that chondrosarcoma is a
      somatomedin-responsive neoplasm and suggest that this tumor may be susceptible to
      interventions directed toward mechanisms that block insulin-like growth factor
      action.

PMID- 8143770
TI  - Anchorage-independent culture of bovine granulosa cells: the effects of basic
      fibroblast growth factor and dibutyryl cAMP on cell division and differentiation.
AB  - During ovarian folliculogenesis granulosa cells divide while in contact with
      stromal cells and other granulosa cells. Following ovulation, however, they cease
      dividing and differentiate into large luteal cells. When cultured in monolayer,
      granulosa cells spontaneously differentiate into luteal cells, thus confounding
      the study of the follicular functions of granulosa cells in vitro, such as cell
      division. We have found that bovine granulosa cells were able to divide in an
      anchorage-independent culture system consisting of soft agar and an overlay of
      methylcellulose. The cells grew in colonies and retained the ultrastructural
      features of follicular granulosa cells. They also secreted an extracellular
      matrix with features of basal lamina. The granulosa cells responded to basic
      fibroblast growth factor (bFGF) in a dose- and time-dependent manner, with a
      three- to five-fold increase (at 50 ng bFGF/ml for 14 days) in the level of DNA
      per dish. This mitogenic effect was inhibited by dibutyryl cAMP (dbcAMP) (1 mM).
      In the presence of dbcAMP the cells hypertrophied considerably, did not secrete
      extracellular matrix, and developed the ultrastructural features of luteal cells.
      They also secreted threefold more progesterone. This system offers the ability to
      study the follicular functions of granulosa cells in culture.

PMID- 8143771
TI  - Transforming growth factor-beta 1 differentially regulates proliferation,
      morphology, and extracellular matrix expression by three neural crest-derived
      neuroblastoma cell lines.
AB  - We reported previously (S. L. Rogers, P. J. Gegick, S. M. Alexander, and P. G.
      McGuire, Dev. Biol. 151, 191-203, 1992) that transforming growth factor-beta 1
      (TGF beta 1) inhibited proliferation, up-regulated fibronectin synthesis, and
      suppressed melanogenesis in a population of quail neural crest cells in vitro.
      Here, we report that cell lines derived from the parent SK-N-SH neuroblastoma
      line (R. A. Ross, B. A. Spengler, and J. L. Biedler, J. Natl. Cancer Inst. 71,
      741-747, 1983) respond differentially to TGF beta 1, and their responses provide
      further insights into the actions of this growth factor on neural crest
      subpopulations. The SH-EP cell line exhibits primarily nonneuronal traits and
      responded to TGF beta 1 with increased thymidine uptake after 6 days of culture,
      increased expression of fibronectin mRNA and protein, and decreased laminin
      synthesis. Many SH-EP cells also acquired a dramatically elongated morphology,
      reminiscent of Schwann cells in culture. Thymidine uptake by the neuronal SY5Y
      cell line was not substantially altered. Neither fibronectin mRNA nor protein was
      detectable in either TGF beta 1-treated or untreated cultures, although laminin
      synthesis was upregulated by the growth factor. In TGF beta 1-treated cultures of
      the intermediate SH-IN cell line, which has been reported to display both
      neuronal and nonneuronal characteristics, there was marked flattening of many
      cells, a steady decrease in thymidine uptake, and increased expression of both
      fibronectin and laminin. The observed responses of SH-IN cells mimic those
      observed in primary neural crest cultures and appear to represent similar
      differentiation toward a mesenchymal phenotype. These results substantiate the
      idea that closely related but diverging neural crest-derived cell types respond
      selectively to TGF beta 1 and demonstrate that these SK-N-SH-derived cell lines
      will be useful in experimental approaches that will allow us to infer mechanisms
      underlying regulation of neural crest differentiation.

PMID- 8143772
TI  - Maturation of myogenic and chondrogenic cells in the presomitic mesoderm of the
      chick embryo.
AB  - The establishment of cells with myogenic or chondrogenic potential is temporally
      and spatially separated from terminal differentiation in the developing chick
      embryo. Both cell types arise from tissue adjacent to the neural tube and
      notochord, the paraxial mesoderm. A cell culture system was developed in order to
      study the maturation and differentiation of myogenic and chondrogenic cells along
      the length of the paraxial mesoderm at different stages of development. Somite
      and segmental plate cells obtained from 36- to 52-h (stages 10-15) embryos were
      plated as a monolayer on substrata of gelatin, fibronectin, or laminin. A
      substratum of gelatin plus fibronectin was most effective in supporting adhesion
      and differentiation. Maximal increase in number of cells in somite cultures
      occurred 24 h earlier than that in segmental plate cultures. Fewer skeletal
      muscle cells and chondroblasts were present in cultures prepared from
      progressively more caudal regions of the paraxial mesoderm and from younger
      embryos. Some cells present within the somites and the rostral two-thirds of the
      stage 13 segmental plate differentiated without replication after placement in
      culture. Only the progeny of cells from its caudal third, and from stage 10
      somites and segmental plates, differentiated under these conditions. The results
      suggest that some myogenic and chondrogenic cells obtain the ability to
      differentiate under these in vitro conditions after stage 10 of development, as
      they occupy more rostral positions within the segmental plate relative to the
      addition of cells at its caudal end. Although some stage 13 segmental plate cells
      form skeletal muscle and cartilage directly after removal from the embryo,
      differentiation is not observed in ovo until these cells are incorporated into
      somites, a minimum of 10 h later. Three-dimensional tissue interactions, and/or
      cell-cell interactions, while not required for segmental plate cells to undergo
      myogenesis and chondrogenesis, may play a role in regulating the timing of
      terminal differentiation within the embryo.

PMID- 8143773
TI  - Cyclin B1 expression in HeLa S3 cells studied by flow cytometry.
AB  - Using a procedure to stain cells simultaneously for cyclin B1 protein and DNA, we
      have examined cyclin B1 expression by flow cytometry in human cells under a
      variety of perturbing and nonperturbing conditions. The method described is
      useful for measuring relative differences in cyclin B level (immunochemically
      detectable epitope) as a function of cell cycle position on an individual cell
      basis and thus to examine cell cycle-related changes in cyclin B expression
      without prior cell synchronization. We show that in HeLaS3 cells, cyclin B1
      accumulates in cells only after they become 4C and have resided in G2 for a short
      period of time. During colcemid-induced mitotic arrest cyclin B1 continues to
      accumulate in HeLa S3 cells, and under specific conditions of aphidicolin-induced
      unbalanced cell growth induced, cyclin B accumulates to supranormal levels prior
      to mitosis. Flow cytometric analysis of cyclin B expression and DNA content
      permits detailed examination of the effects of cell cycle perturbations on cyclin
      B expression under a variety of conditions.

PMID- 8143774
TI  - Interphase AgNOR quantity is not related to DNA content in 11 established human
      cancer cell lines.
AB  - The relationship between interphase AgNOR quantity and DNA ploidy was evaluated
      in 11 cell lines derived from human tumors of different origin. Interphase AgNOR
      quantity was measured by morphometric image analysis and DNA content by
      cytofluorometry. The mean interphase AgNOR area ranged from 5.56 to 21.12 microns
      2 and DNA ploidy from 2.05 to 3.30c. The interphase AgNOR value and DNA content
      were not significantly related (r = 0.23, P = 0.52). No significant correlation
      was found between DNA content and cell doubling time, whereas a strict
      relationship was confirmed to exist between interphase AgNOR quantity and
      rapidity of cell proliferation.

PMID- 8143775
TI  - Comparison of PDGF-AA- and PDGF-BB-induced phosphoinositide formation in human
      and mouse fibroblasts.
AB  - In certain cells, such as human fibroblasts (AG 1523), there is a clear
      difference in the cell motility response induced by the different isoforms of
      platelet-derived growth factor (PDGF). PDGF-BB induces extensive actin
      reorganization and is a potent chemotactic agent, whereas PDGF-AA has a limited
      effect on actin reorganization and is not chemotactic. In the present study, we
      wanted to compare these effects on cell motility with the effects of the PDGF
      isoforms on phosphoinositide (PtdIns) turnover. We find that stimulation of serum
      starved AG 1523 cells with PDGF-AA or PDGF-BB caused an initial increase of the
      phosphatidylinositol phosphate and bisphosphate (PtdInsP and PtdInsP2) pools,
      suggesting that activation of the phosphoinositide kinases is an initial response
      to PDGF stimulation. Despite a lower number of PDGF alpha-receptors than beta
      receptors on these cells, the initial formation of PtdInsP and PtdInsP2 appears
      to be stimulated to a similar degree by the two PDGF isoforms. In contrast,
      PtdInsP2 hydrolysis, indirectly measured as formation of phosphatidic acid, was
      correlated to the number of receptors. During prolonged exposure to PDGF-BB the
      stimulated PtdIns turnover remained at a high level, whereas the effect of PDGF
      AA appeared more transient. A marked increase in the synthesis of a component
      migrating as phosphatidylinositol trisphosphate (PtdInsP3) was also detected
      after stimulation with PDGF-BB for 5 min. With PDGF-AA minor amounts were found,
      indicating that activation of the PtdIns 3'-kinase occurs also via the PDGF alpha
      receptor. Stimulation with PDGF-BB, but not -AA, also induced a 50% decrease in
      lyso-PtdIns. In murine fibroblasts (Swiss 3T3), where the two PDGF isoforms have
      a similar effect on cell motility, the two PDGF isoforms also similarly induced
      PtdIns turnover, PtdInsP3 formation, and a decrease in lyso-PtdIns. Thus, there
      seems to be a correlation between PDGF-induced PtdIns turnover and PDGF-induced
      actin reorganization. This is compatible with previous evidence suggesting the
      microfilament formation is directly linked to an increased turnover of
      polyphosphoinositides in stimulated cells.

PMID- 8143776
TI  - Apoptosis is induced at nonpermissive temperature by a transient increase in p53
      in cell lines immortalized with temperature-sensitive SV40 large T-antigen gene.
AB  - Hepatocyte (TLR2) and kidney tubule (TKC2) cell lines established from
      temperature-sensitive (ts) SV40 T-antigen gene transgenic mice not only were
      arrested in growth, but also exhibited cell death at nonpermissive temperature
      (39 degrees C). The cell death was determined to be caused by apoptosis from
      observations of nuclear fragmentation and DNA fragmentation. These cell lines
      contained relatively high levels of wild-type p53 which formed complexes with T
      antigen at permissive temperature (33 degrees C), but after shift to a
      nonpermissive temperature, the inactivation of T-antigens led to the liberation
      of an abundance of p53 proteins from the complexes, apparently inducing
      apoptosis.

PMID- 8143777
TI  - Dexamethasone enhancement of betaglycan (TGF-beta type III receptor) gene
      expression in osteoblast-like cells.
AB  - Betaglycan (type III transforming growth factor-beta (TGF-beta) receptor) is a
      cell surface heparan/chondroitin sulfate proteoglycan that binds TGF-beta via its
      core protein and is abundantly expressed in osteoblastic cells. A previous report
      (Centrella et al., Mol. Cell. Biol. 11, 4490-4496, 1991) showed post
      translational enhancement by glucocorticoid of TGF-beta binding to betaglycan.
      Upon the availability of the betaglycan cDNA, we investigated the effects of a
      glucocorticoid analogue, dexamethasone, on the regulation of betaglycan
      expression in osteoblast-like cells. Betaglycan mRNA was expressed as an
      approximately 6-kb band in MC3T3-E1 cells. The betaglycan mRNA level was enhanced
      severalfold by dexamethasone in these cells. The effect of dexamethasone on the
      betaglycan mRNA level was observed within 9 h and was sustained at least up to 48
      h. The dexamethasone effect was dose-dependent, with a saturation concentration
      at 10(-7) M. Among the steroid hormones examined, dexamethasone exhibited the
      most potent effect on betaglycan mRNA expression, while retinoic acid also
      enhanced it moderately. Dexamethasone enhancement of betaglycan mRNA expression
      was blocked by actinomycin D, but it was not blocked by cycloheximide. Cross
      linking experiments showed that dexamethasone treatment increased the binding of
      radiolabeled TGF-beta 1 to betaglycan, but did not affect binding to the type II
      receptor. A similar dexamethasone enhancement of betaglycan mRNA expression was
      also observed in a preosteoblast-like cell line, RCT1. These results suggest that
      dexamethasone enhances betaglycan expression at least in part via transcriptional
      events in osteoblasts and this would be one of the target points of
      glucocorticoid regulation of bone metabolism.

PMID- 8143778
TI  - Generation and immunohistological characterization of monoclonal antibodies
      against rat ovarian antigens.
AB  - Hybridoma cell lines were obtained from mouse splenocytes sensitized to granulosa
      cells and oocytes collected from rat ovaries at the time of gonadotropin
      stimulation. Each of the Mabs was characterized by its cell type-specific binding
      reaction using immunofluorescence, avidin-biotin-peroxidase complex, immunogold
      silver staining, and some of the Mabs were characterized by electron microscopic
      immunocytochemistry. Mabs were divided into four classes. On the basis of the
      immunohistochemical results and a secondary assay, ELISA with conditioned medium
      containing granulosa cell-secreted proteins (GSPs) we have concluded: (a) The
      Mabs (Class 1) reacted with GSPs and recognized antigens located on the plasma
      membrane of granulosa cells. The reaction depends both on the degree of
      follicular development and on the position of the cells within the follicles. (b)
      The general pattern of binding of Mab 2E9 (Class 2) was restricted only to the
      germinal vesicles of oocytes in antral and Graafian follicles. This result
      indicated a nuclear modification during the progressive phases of oocyte growth.
      (c) Same antigens recognized by Mabs from Class 3 and 4 were distributed in the
      cytoplasm of the oocytes and are a constant feature of all growing oocytes
      displaying a redistribution during meiotic maturation.

PMID- 8143779
TI  - Induction of a common pathway of apoptosis by staurosporine.
AB  - The present observations show that staurosporine can rapidly trigger both the
      morphological changes and intranucleosomal DNA fragmentation typical of
      apoptosis. This occurred in a number of cell lines from various origins
      regardless of the state of differentiation and cell cycle phase, suggesting the
      presence of a common inducible suicide pathway. The broad apoptotic activity of
      staurosporine appears to be unique among other protein kinase or phosphatase
      inhibitors we tested. Results obtained in a cell-free assay suggest that
      cytoplasmic proteins directly modulated by staurosporine may be involved in a
      ubiquitous signal for the induction of DNA fragmentation and apoptosis.

PMID- 8143780
TI  - Lithium induces apoptosis in immature cerebellar granule cells but promotes
      survival of mature neurons.
AB  - Lithium (Li+) has been used in the treatment of manic-depressive disorders for
      several decades. More recently, Li+ has been shown to affect the signaling
      pathway of various neurotransmitters and growth/neurotrophic factors. We examined
      the effect of Li+ on the survival of cerebellar granule neurons in culture.
      Treatment of immature granule cells with Li+ resulted in programmed cell death
      (apoptosis). The death process is accompanied by DNA fragmentation, a hallmark of
      apoptosis. Following maturation in vitro, granule neurons are dependent on
      elevated concentrations of extracellular potassium ([K+]o) for survival. Lowering
      of [K+]o to physiological levels induces apoptosis. Surprisingly, Li+ prevents
      death of mature neurons caused by low [K+]o. Moreover, the concentration range at
      which Li+ exerts its protective effect is the same as that at which it induces
      apoptosis in immature neurons. Thus, a single agent under similar extracellular
      conditions has opposing effects on survival, depending on the developmental
      status of the neuron.

PMID- 8143781
TI  - Apoptosis is dependent on intracellular zinc and independent of intracellular
      calcium in lymphocytes.
AB  - Changes in intracellular Ca2+ concentration ([Ca2+]i) are believed to have a
      crucial role in triggering apoptosis, the process whereby cells are eliminated
      during tissue turnover, hormone-mediated tissue reabsorption, clonal selection in
      the thymus, T cell-mediated cytotoxic reactions, and many other physiological and
      pathological processes. In the present report we have explored the role of
      intracellular Ca2+ and Zn2+ in the regulation of apoptosis in peripheral blood
      lymphocytes (PBL). Unless they were stimulated by a mitogen, e.g.,
      phytohemagglutinin (PHA), PBL showed typical apoptotic changes (nuclear
      condensation and DNA fragmentation) after a 48- to 72-h culture. Neither a
      sustained nor a transient increase in [Ca2+]i induced by the Ca2+ ionophore
      ionomycin in the presence or absence of extracellular Ca2+, respectively, was
      able to trigger DNA fragmentation. On the contrary, [Ca2+]i chelation to a level
      10- to 20-fold lower than physiological resting levels induced DNA cleavage into
      nucleosome-size DNA fragments. DNA cleavage was also induced by incubation in the
      presence of the intracellular, membrane-permeant Zn2+ chelator N,N,N',N'
      tetrakis(2-pyridyl-methyl)ethylenediamine. Total intracellular Zn2+ content was
      increased by mitogenic stimulation with PHA and decreased by treatment of PBL
      cultures with dexamethasone or extracellular ATP, stimuli known to trigger
      apoptosis in lymphocytes. Our results suggest that Zn2+ rather than Ca2+ could be
      a key intracellular regulator of apoptosis.

PMID- 8143782
TI  - Phenomena of spontaneous proliferation, differentiation, and apoptosis in primary
      culture of leukemic lymphocytes.
AB  - The proliferative capacity of lymphocytes from peripheral blood of bovine with
      chronic lymphocytic leukemia (CLL) in vitro was investigated. We have shown
      earlier that CLL cells spontaneously proliferate in serum-free medium in the
      absence of added growth factors and mitogenic stimulation; autocrine growth
      factors provide the growth-initiating signal for CLL cells. The results of the
      present study showed that bovine serum albumin or fetal calf serum greatly
      enhanced the number of CLL cells incorporating [3H]thymidine. Although some CLL
      cells proceeded through more than one cell cycle, proliferation of CLL cells in
      culture was temporary. On the other hand, it was shown that CLL cells
      differentiated spontaneously in culture. This differentiation was characterized
      by the appearance of plasmacytoid cells possessing cytoplasmic immunoglobulins
      that coincided with the cessation of cell proliferation. Moreover, together with
      spontaneous proliferation and differentiation, the phenomenon of programmed cell
      death (apoptosis) was found, as was evidenced by the appearance of apoptotic
      bodies as well as DNA fragmentation. The findings indicate that the loss of
      proliferative potential of CLL cells in culture may be a consequence of their
      differentiation and/or apoptosis in vitro. CLL cells, with an autocrine growth
      mechanism, spontaneous differentiation, and apoptosis in vitro, provide a new
      model system for studies of the relationship between cellular proto-oncogene
      expression and inhibition of growth and/or induction of differentiation.

PMID- 8143783
TI  - Expression of functional growth hormone receptor in a mouse L cell line infected
      with recombinant vaccinia virus.
AB  - The growth hormone receptor is a member of a large family of receptors including
      the receptors for prolactin and interleukins. Upon binding to one molecule of
      growth hormone two growth hormone receptor polypeptides dimerize. We have
      expressed the rabbit growth hormone receptor DNA in transfected mouse L cells
      infected with polymerase T7-producing vaccinia virus. The growth hormone receptor
      was synthesized as a 85-kDa protein and transported to the cell surface. Western
      blotting and metabolic labeling combined with immunoprecipitation using a rabbit
      antibody probably directed against the cytosolic domain of the receptor showed
      that its expression was dependent on both transfection of the growth hormone
      receptor DNA and vaccinia infection. Binding studies with 125I-labeled growth
      hormone demonstrated specific binding sites at the cell surface 20 h after
      transfection. Permeabilization with saponin showed that the growth hormone
      receptor binding sites were almost exclusively present at the cell surface with
      little intracellularly. Chemical crosslinking of the 125I-growth hormone complex
      resulted in a 180-kDa complex which could specifically be immunoprecipitated with
      the antiserum. Electron microscopic immunocytochemistry confirmed the presence of
      growth hormone receptor at the cell surface. Furthermore, specific growth hormone
      receptor antigen was also associated with intracellular membranes. These results
      thus show that this transient transfection system will be useful for cell
      biological studies of growth hormone receptor regulation.

PMID- 8143784
TI  - The alpha 6 beta 4 integrin is a receptor for both laminin and kalinin.
AB  - Previously, we have establish K562 transfectants that express either alpha 6A
      beta 1 or alpha 6B beta 1 (K alpha 6A or K alpha 6B) on their surface. Both cell
      lines bind to laminin and kalinin after treatment with the beta 1-stimulatory
      antibody TS2/16. Here we introduce the full-length beta 4 cDNA into the alpha 6A-
      and alpha 6B-expressing K562 cells and selected stably transfected cells. The
      beta 4 subunit was expressed on the surface of both transfectants and it formed
      dimers with the alpha 6A or alpha 6B subunits. Immunoprecipitation and
      preclearing analyses revealed that both transfectants expressed alpha 6 beta 1,
      in addition to alpha 6 beta 4. While K alpha 6A and K alpha 6B cells required
      TS2/16 stimulation for binding to laminin or kalinin, adhesion of the
      unstimulated beta 4-transfected K alpha 6A and K alpha 6B cells to these matrix
      components was already substantial. This adhesion was mediated by both alpha 6
      beta 1 and alpha 6 beta 4 since it was completely blocked by an alpha 6-specific
      antibody or by a combination of anti-beta 1 and anti-beta 4 antibodies, but only
      partially by either of these latter two antibodies alone. Adhesion to laminin was
      completely blocked by an antiserum to laminin fragment E8 as was the adhesion to
      kalinin by an antibody to kalinin, demonstrating the specificity of adhesion.
      Both transfectants always adhered more strongly to kalinin than to laminin.
      Furthermore, binding to kalinin was less well blocked by antibodies to beta 4
      than binding to laminin, indicating that the affinity of alpha 6 beta 4 for
      kalinin is higher than that for laminin. The fact that alpha 6 beta 1 mediated
      adhesion without TS2/16 stimulation on the beta 4-transfected K alpha 6A and K
      alpha 6B cells suggests that some activation of alpha 6 beta 1 had occurred in
      these cells, even though binding was increased when they were actively stimulated
      by the antibody TS2/16. Finally, we show that Mn2+ induced binding of solubilized
      alpha 6 beta 4 to matrix containing kalinin, deposited by the murine cell line
      RAC-11P/SD. This binding was inhibited by the anti-alpha 6 mAb GoH3. Together,
      these results indicate that both alpha 6 beta 1 and alpha 6 beta 4 are receptors
      for laminin and kalinin and that there are no differences in ligand specificity
      between the A and B variants of the alpha 6 subunit when associated with either
      beta 1 or beta 4.

PMID- 8143785
TI  - Thrombin stimulates fibroblast-mediated collagen lattice contraction by its
      proteolytically activated receptor.
AB  - Fibroblast contraction is proposed to play an important role in tissue
      contraction during events such as wound healing. Thrombin has been implicated to
      promote force generation in fibroblasts; however, its extracellular mode of
      action is unclear. The purpose of this study was to determine the role thrombin
      and the activation of its receptor plays in promoting the contraction of human
      fibroblasts in an in vitro collagen lattice contraction assay. Human alpha
      thrombin promoted fibroblast contraction in a dose-dependent manner with maximal
      activity at 0.2 nM. In contrast, both hirudin-alpha-thrombin and D-phenylalanyl-L
      propyl-L-arginyl chloromethyl ketone-alpha-thrombin, which lack enzymatic
      activity, failed to elicit fibroblast contraction. Thus, the enzymatic activity
      of thrombin appears to be necessary for promotion of fibroblast contraction.
      Northern analysis confirmed that these human fibroblasts expressed mRNA for the
      human alpha-thrombin receptor. Moreover, the synthetic peptide (SFLLRNPND-KYEPF)
      representing the "tethered ligand" portion of the activated alpha-thrombin
      receptor promoted fibroblast contraction, while a control isomer peptide, in
      which the first two amino acids were reversed, failed to elicit this response.
      These findings indicate that alpha-thrombin promotes the contraction of adult
      human fibroblasts and that cleavage of the human alpha-thrombin receptor is
      sufficient to produce this response.

PMID- 8143786
TI  - Platelet-derived growth factor increases the activity of the promoter of the
      insulin-like growth factor-1 (IGF-1) receptor gene.
AB  - Stimulation by platelet-derived growth factor (PDGF) is known to increase the
      number of IGF-I binding sites in cells in culture. We show here that PDGF also
      increases the levels of IGF-1 receptor mRNA. Using cell lines stably transfected
      with an expression plasmid in which the reporter luciferase gene is under the
      control of the rat IGF-1 receptor gene promoter, we find that PDGF increases the
      activity of this promoter. A short IGF-1 receptor gene promoter, comprising about
      100 base pairs of the sequence immediately upstream of the initiation of
      transcription site, is sufficient for a response to the stimulatory action of
      PDGF. These results suggest that an increase in RNA levels and in promoter
      activity may play an important role in the increase in IGF-1 receptor levels that
      occurs after stimulation by PDGF.

PMID- 8143787
TI  - Identification of a 115-kDa protein from muscle tissues: expression of a novel
      nonmuscle alpha-actinin in vascular endothelial cells.
AB  - A novel nonmuscle alpha-actinin from chicken lung tissue is distinct from
      reported nonmuscle and muscle alpha-actinins in its mobility on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the presence of 6 M urea
      (apparent molecular mass is 115 kDa) and its Ca(2+)-sensitivity in actin binding
      (M. Imamura and T. Masaki, J. Biol. Chem. 267, 25927-25933, 1992). SDS-PAGE
      analysis of extract from chicken gizzard smooth muscle tissue in the presence of
      urea showed the existence of a protein migrating at 115 kDa. Analyses of
      proteolytic digestion and partial amino acid sequence revealed that the latter
      115-kDa protein is identical or very similar to the Ca(2+)-insensitive lung alpha
      actinin. We prepared an antibody specific for the 115-kDa protein by affinity
      column coupled with the purified lung alpha-actinin, and the expression and
      distribution of the 115-kDa protein in muscle tissues were examined.
      Immunoblotting and immunofluorescence microscopy demonstrated that the 115-kDa
      protein was expressed in heart and pectoralis muscle tissues as well as in
      gizzard. Double-fluorescence staining with the anti-115-kDa protein antibody and
      anti-muscle alpha-actinin antibody indicated that the 115-kDa protein was
      localized in tubular structures along the axes of muscle fibers, whose diameter
      was 3.5-5 microns. The tubular structure did not respond to the muscle cells.
      Vascular-labeling analysis with carbon dye showed that the staining with anti-115
      kDa protein antibody was located along the inside of the vascular wall. These
      results indicated that the Ca(2+)-insensitive alpha-actinin was expressed in
      vascular endothelial cells and suggested that its Ca(2+)-sensitivity was related
      to the function of the endothelial cells.

PMID- 8143788
TI  - Identification of the ubiquitous human desmoglein, Dsg2, and the expression
      catalogue of the desmoglein subfamily of desmosomal cadherins.
AB  - Desmosomes are junctions between epithelial, myocardiac, and certain other kinds
      of cells. They represent plasma membrane domains enriched in specific
      transmembrane glycoproteins, notably desmoglein (Dsg) and desmocollin (Dsc), both
      of which have recently been identified as members of the larger family of Ca(2+)
      dependent cell adhesion molecules, the cadherins. Previously described forms of
      desmoglein have been isolated as proteins and cloned as cDNAs from epidermis and
      related stratified epithelia but have not been detected in the majority of other
      desmosome-containing tissues and cell culture lines. Here we present the complete
      cDNA-derived amino acid (aa) sequence of a different desmoglein polypeptide,
      termed Dsg2 (1069 aa, mol wt 116,760) and its precursor molecule (1117 aa, mol wt
      122,384), which occurs in all human and bovine desmosome-producing tissues,
      tumors, and cell lines examined, epithelial as well as nonepithelial ones. We
      conclude that Dsg2, the largest molecule in this protein family, is the
      fundamental desmoglein common to all desmosome-possessing tissues, including
      simple epithelia and myocardium, and many cell cultures. Furthermore, in several
      tissues and cell lines Dsg2 is the only Dsg isoform detected so far. By contrast,
      the epidermal isoforms Dsg1 and Dsg3 are restricted to certain specialized
      epithelia, mostly stratified squamous ones. The importance of the junction
      specific cadherin Dsg2 in tissue formation and carcinogenesis as well as in the
      development of autoimmune diseases of the Pemphigus type is discussed. In
      addition, we propose to use Dsg2 as a general marker common to all epithelial
      cells and tumors and to use the specific pattern of occurrence of Dsg and Dsc
      isoforms as an additional criterion for cell typing in tumor diagnosis.

PMID- 8143789
TI  - Combinatorial action of cAMP and phorbol ester on synergistic expression of the
      human activin A gene.
AB  - A number of synergistic effects of cAMP and 12-O-tetradecanoylphorbol 13-acetate
      (TPA) that mimic diacylglycerol function on transcription have been studied,
      implying the existence of "cross-talk" regulation. However, there is still less
      information available on the combinatorial action of such signal transduction
      convergence on cellular gene expression. In the present study, we have first
      examined the synergistic effects of cAMP and TPA on the gene expression of
      activin A, an important regulator of cell growth and differentiation, and next we
      revealed their ordered action in HT1080 cells. A combined treatment of these
      cells with cAMP and TPA synergistically increased accumulation of the activin A
      mRNA. Interestingly, this synergistic response also occurred when cells were
      treated with cAMP following short preexposure to TPA. In contrast, the increase
      in activin A mRNA levels in those cells preexposed to cAMP with subsequent
      treatment by TPA was limited to that caused by TPA alone, suggesting an
      importance of ordered stimulation. Addition of cycloheximide (CHX), an inhibitor
      of protein synthesis, to cultures led to superinduction of activin mRNA
      transcripts regardless of TPA exposure, but significantly attenuated the cAMP
      induced mRNA levels. Moreover, the observed synergism between TPA and cAMP was
      not inhibited by CHX, showing that de novo protein synthesis was required for the
      mRNA induction by cAMP but not for those induced by TPA or those induced by both.
      These results demonstrated that transient stimulation of HT1080 cells by TPA with
      subsequent exposure to cAMP is sufficient for the synergistic induction of the
      activin A gene expression and suggested that the combinatorial action of TPA
      followed by cAMP stimulation plays an important role in regulating activin
      synthesis in these cells.

PMID- 8143790
TI  - Is the coiled body involved in nucleolar functions?
AB  - Coiled bodies (CBs) are structural constituents observed in nuclei of most
      eukaryotic cells. They usually occur in the nucleoplasm as well as in contact
      with the nucleolar surface. In this work we studied the hepatocyte nuclei of
      hibernating dormice in order to investigate possible modifications of CBs along
      the seasonal cycle. CBs were abundant during hibernation and rapidly disappeared
      upon arousal from hibernation. Moreover, CBs were frequently found to be
      integrated into the nucleolar body. Immunocytochemical analyses showed that CBs
      contain nucleoplasmic as well as nucleolar RNA-processing factors, suggesting an
      "ambiguous" role for this organelle in the nuclear functions.

PMID- 8143791
TI  - Selective hypermethylation of transcribed nucleosomal DNA by sodium butyrate.
AB  - Previous studies have shown that treatment of cultured fibroblasts with
      millimolar concentrations of sodium butyrate results in increased methylation of
      cytosine residues in DNA. In this study, active nucleosomes were fractionated
      from the inactive ones by organomercurial agarose column chromatography. DNA in
      each fraction was hydrolyzed to its constituent bases and subjected to HPLC
      analysis in order to determine the 5-methylcytosine content. In control cells,
      the active nucleosomal DNA was hypomethylated (0.97 +/- 0.27% 5-methyleytosine)
      when compared with the inactive DNA fraction (1.61 +/- 0.15%). This result was
      not unexpected since DNA hypermethylation is generally associated with gene
      inactivation. Treatment of cells with sodium butyrate, however, resulted in
      increased methylation of the active nucleosomal DNA such that it was comparable
      to that of the inactive fraction of control cells (1.73 +/- 0.02% 5
      methylcytosine). A much smaller increase in 5-methylcytosine content was detected
      in the inactive DNA fraction of sodium butyrate-treated cells (from 1.61 to
      1.89%). Removal of the sodium butyrate followed by a chase in butyrate-free
      medium for up to 120 h failed to reverse the butyrate-induced hypermethylation.
      Reversal was achieved only after continuous culture in butyrate-free medium for
      10 days.

PMID- 8143792
TI  - Homologous recombination.

PMID- 8143793
TI  - Structure and function of RecA-DNA complexes.
AB  - While the E. coli RecA protein has been the most intensively studied enzyme of
      homologous recombination, the unusual RecA-DNA filament has stood alone until
      very recently. It now appears that this protein is part of a universal family
      that spans all of biology, and the filament that is formed by the protein on DNA
      is a universal structure. With RecA's role in recombination given new and greatly
      increased significance, we focus in this review on the energetics of the RecA
      mediated strand exchange and the relation between the energetics and
      recombination spanning heterologous inserts.

PMID- 8143794
TI  - In vitro reconstitution of homologous recombination reactions.
AB  - The proteins essential to homologous recombination in E. coli have been purified
      and their individual activities have been identified, permitting biochemical
      reconstitution of steps that comprise the cellular recombination process. This
      review focuses on the biochemical events responsible for the initiation and
      homologous pairing steps of genetic recombination. The properties of an in vitro
      recombination reaction that requires the concerted action of recA, recBCD, and
      SSB proteins and that is stimulated by the recombination hotspot, Chi(chi), are
      described. The recBCD enzyme serves as the initiator of this reaction; its DNA
      helicase activity produces single-stranded DNA that is used by the recA protein
      to promote homologous pairing and DNA strand invasion of supercoiled (recipient)
      DNA. The SSB protein acts to trap the single-stranded DNA produced by recBCD
      enzyme and to facilitate pairing by the recA protein. The chi regulatory sequence
      acts in cis by attenuating the nuclease, but not the helicase, activity of recBCD
      enzyme. This attenuation assures the preservation of ssDNA produced by the DNA
      helicase activity and is responsible for the simulation in vitro and, presumably,
      in vivo. The attenuation of nuclease activity by chi results in the loss or
      functional inactivation of the recD subunit.

PMID- 8143795
TI  - Processing of Holliday junctions by the Escherichia coli RuvA, RuvB, RuvC and
      RecG proteins.
AB  - Recent work has led to significant advances in our understanding of the late
      steps of genetic recombination and the post-replicational repair of DNA. The RuvA
      and RuvB proteins have been shown to interact with recombination intermediates
      and catalyse the branch migration of Holliday junctions. Although both proteins
      are required for branch migration, each plays a defined role with RuvA acting as
      a specificity factor that directs RuvB (an ATPase) to the junction. The RuvB
      ATPase provides the motor for branch migration. The next step is catalysed by
      RuvC protein which recognises Holliday junctions and promotes their resolution by
      endonucleolytic cleavage. New data indicates an alternative pathway for Holliday
      junction processing. This pathway involves RecG, a branch migration protein which
      is functionally analogous to RuvAB, and a protein (activated by a rus mutation)
      which works with RecG to process intermediates independently of RuvA, RuvB and
      RuvC.

PMID- 8143796
TI  - The search for the right partner: homologous pairing and DNA strand exchange
      proteins in eukaryotes.
AB  - Finding the right partner is a central problem in homologous recombination.
      Common to all models for general recombination is a homologous pairing and DNA
      strand exchange step. In prokaryotes this process has mainly been studied with
      the RecA protein of Escherichia coli. Two approaches have been used to find
      homologous pairing and DNA strand exchange proteins in eukaryotes. A biochemical
      approach has resulted in numerous proteins from various organisms. Almost all of
      these proteins are biochemically fundamentally different from RecA. The in vivo
      role of these proteins is largely not understood. A molecular-genetical approach
      has identified structural homologs to the E. coli RecA protein in the yeast
      Saccharomyces cerevisiae and subsequently in other organisms including other
      fungi, mammals, birds, and plants. The biochemistry of the eukaryotic RecA
      homologs is largely unsolved. For the fungal RecA homologs (S. cerevisiae RAD51,
      RAD55, RAD57, DMC1; Schizosaccharomyces pombe rad51; Neurospora crassa mei3) a
      role in homologous recombination and recombinational repair is evident. Besides
      recombination, homologous pairing proteins might be involved in other cellular
      processes like chromosome pairing or gene inactivation.

PMID- 8143797
TI  - Hotspots of homologous recombination.
AB  - Homologous recombination occurs at higher than average frequency at and near
      hotspots. Hotspots are special nucleotide sequences recognized by proteins that
      promote, directly or indirectly, a rate limiting step of recombination. This
      review focuses on two well-studied examples, the Chi sites of the bacterium
      Escherichia coli and the M26 site of the fission yeast Schizosaccharomyces pombe.
      Chi, 5' G-C-T-G-G-T-G-G 3', is recognized by the RecBCD enzyme, which nicks the
      DNA near Chi and produces a 3'-ended single-stranded DNA 'tail'; this tail is a
      potent substrate for homologous pairing by RecA and single-stranded DNA binding
      proteins. M26, 5' A-T-G-A-C-G-T 3', is recognized by a heterodimeric protein and
      stimulates, by an as-yet-unknown mechanism, meiotic recombination at and near the
      ade6 gene. Additional hotspots in bacteria, fungi, and mammals enhance
      recombination directly or indirectly via a variety of mechanisms. Although
      hotspots are widespread among organisms, the biological role of their localized
      enhancement of recombination remains a matter of speculation.

PMID- 8143798
TI  - Polarity of meiotic gene conversion in fungi: contrasting views.
AB  - The frequency of meiotic gene conversion often varies linearly from one end of
      the gene to the other. This phenomenon has been called 'polarity'. In this
      review, we will primarily studies of polarity that have been done in the yeast
      Saccharomyces cerevisiae (ARG4 and HIS4 loci) and in Ascobolus (b2 locus) with an
      emphasis on possible mechanisms. The genetic and physical data obtained at these
      'hotspots' of recombination strongly suggests that the formation of a polarity
      gradient reflects both the frequency of heteroduplex formation and the processing
      of this recombination intermediate by mismatch-repair-dependent processes.

PMID- 8143799
TI  - Some features of base pair mismatch repair and its role in the formation of
      genetic recombinants.
AB  - For the formation of recombinants involving closely linked markers, two distinct
      processes play a role. The recombinational interaction between homologous DNA
      molecules results in the presence of heteroduplex DNA joining the parental
      components of the recombinant. The presence of markers distinguishing the parents
      in the region of heteroduplex DNA can result in base pair mismatches. The post
      recombination repair of such mismatches can contribute to the separation of
      closely linked markers. The processes responsible for such repair also play roles
      in mutation avoidance. The specificities, functions and contribution to the
      formation of recombinants for closely linked markers of the processes in
      Escherichia coli are described.

PMID- 8143801
TI  - Gene conversion in the chicken immunoglobulin locus: a paradigm of homologous
      recombination in higher eukaryotes.
AB  - Gene conversion was first defined in yeast as a type of homologous recombination
      in which the donor sequence does not change. In chicken B cells, gene conversion
      builds the antigen receptor repertoire by introducing sequence diversity into the
      immunoglobulin genes. Immunoglobulin gene conversion continues at high frequency
      in an avian leukosis virus induced chicken B cell line. This cell line can be
      modified by homologous integration of transfected DNA constructs offering a model
      system for studying gene conversion in higher eukaryotes. In search for genes
      which might participate in chicken immunoglobulin gene conversion, we have
      identified chicken counterparts of the yeast RAD51, RAD52, and RAD54 genes.
      Disruption and overexpression of these genes in the chicken B cell line may
      clarify their role in gene conversion and gene targeting.

PMID- 8143800
TI  - Transcription, topoisomerases and recombination.
AB  - Transcription, DNA topoisomerases and genetic recombination are interrelated for
      several structural reasons. Transcription can affect DNA topology, resulting in
      effects on recombination. It can also affect the chromatin structure in which the
      DNA resides. Topoisomerases can affect DNA and/or chromatin structure influencing
      the recombination potential at a given site. Here we briefly review the extent to
      which homologous direct repeat recombination and site-specific recombination in
      eukaryotes are affected by transcription and topoisomerases. In some cases,
      transcription or the absence of topoisomerases have little or no effect on
      recombination. In others, they are important components in the recombinational
      process. The common denominator of any effects of transcription and
      topoisomerases on recombination is their shared role in altering DNA topology.

PMID- 8143802
TI  - Cytological aspects of meiotic recombination.
AB  - This article reviews current views on the mechanisms of meiotic homology
      searching and recombination. It discusses the relationship between molecular
      events at meiotic prophase and concomitant cytological processes. The role of the
      synaptonemal complex and other meiosis-specific structures is discussed. Whereas
      the relationship of crossovers, late recombination nodules, and chiasmata is well
      established, there is still some controversy about the temporal and causal
      relationships between double strand breaks, homologue recognition,
      heteroduplexes, early nodules and presynaptic alignment.

PMID- 8143805
TI  - Compendium of food additive specifications. Addendum 2. Joint FAO/WHO Expert
      Committee on Food Additives 41st Session.

PMID- 8143806
TI  - "Occupational asthma": a matter of concern.

PMID- 8143804
TI  - Gene inactivation triggered by recognition between DNA repeats.
AB  - This chapter focuses on phenomena of gene inactivation resulting from the
      presence of repeated gene copies within the genome of plants and fungi, and on
      their possible relationships to homologous DNA-DNA interactions. Emphasis is
      given to two related premeiotic processes: Methylation Induced Premeiotically
      (MIP) and Repeat-Induced Point mutation (RIP) which take place in the fungi
      Ascobolus immersus and Neurospora crassa, respectively. The relationships between
      these processes and genetic recombination are discussed.

PMID- 8143803
TI  - Homologous recombination in fission yeast: absence of crossover interference and
      synaptonemal complex.
AB  - The study of homologous recombination in the fission yeast Schizosaccharomyces
      pombe has recently been extended to the cytological analysis of meiotic prophase.
      Unlike in most eukaryotes no tripartite SC structure is detectable, but linear
      elements resembling axial cores of other eukaryotes are retained. They may be
      indispensable for meiotic recombination and proper chromosome segregation in
      meiosis I. In addition fission yeast shows interesting features of chromosome
      organization in vegetative and meiotic cells: Centromeres and telomeres cluster
      and associate with the spindle pole body. The special properties of fission yeast
      meiosis correlate with the absence of crossover interference in meiotic
      recombination. These findings are discussed. In addition homologous recombination
      in fission yeast is reviewed briefly.

PMID- 8143807
TI  - Two family outbreaks of Chlamydia pneumoniae infection.
AB  - During autumn 1992, we observed two unrelated family outbreaks of Chlamydia
      pneumoniae infection. Family A consisted of grandmother (aged 77 yrs), father
      (aged 41 yrs), mother (aged 38 yrs), daughter (aged 10 yrs), and two sons (aged 6
      yrs and 3 months, respectively). The grandmother and daughter suffered from
      pneumonia, father from pharyngitis and bronchitis and the older son from mild
      bronchitis. No symptoms were recorded in the mother and younger son. Symptomatic
      subjects showed a fourfold increase in immunoglobulin G (IgG) titre for Chlamydia
      pneumoniae, determined by a microimmunofluorescence test with specific antigen
      (TW-183). Other serological studies against Mycoplasma pneumonia, Legionella
      pneumophila, influenza virus type A and B, adenovirus and respiratory syncytial
      virus (RSV) were negative. Sputum culture gave a positive result for Haemophilus
      influenzae, colony forming units (cfu) = 10(4).ml-1 in the grandmother. No serum
      positivity was recorded in the mother and younger son, who remained asymptomatic.
      All symptomatic patients were successfully treated with macrolides. Family B
      consisted of mother (aged 63 yrs) and daughter (aged 36 yrs). Both suffered from
      Chlamydia pneumoniae pneumonia. Diagnosis was made by means of serological
      microimmunofluorescence test, and direct identification using an indirect
      immunofluorescence test on pharyngeal swab. Sputum culture and other serological
      tests remained negative. Both patients were successfully treated with macrolides.
      These observations emphasize the relevance of Chlamydia pneumoniae in family
      cluster respiratory infections.

PMID- 8143808
TI  - A comparison of respiratory function in Afro-Caribbean and Caucasian infants.
AB  - Race is recognized as an important determinant of lung function in children and
      adults, but limited data exist for infants. Accurate interpretation of lung
      function tests during the neonatal period may depend on appropriate values for
      predicting normality. The aim of this study was to compare tidal breathing
      parameters, Hering-Breuer reflex (HBR) activity, and total respiratory compliance
      (Crs) in healthy newborn caucasian (white) and Afro-Caribbean (black) infants, to
      determine whether separate reference values were required for these two ethnic
      groups. Respiratory function was measured in 33 healthy black infants, 18 of whom
      were premature, and 33 healthy white infants matched for sex, gestational age,
      weight, postnatal age, and maternal smoking during pregnancy. There were no
      significant paired differences between black and white infants with respect to
      minute ventilation, respiratory frequency, the ratio of time to reach peak
      expiratory flow to total expiratory time, or HBR activity. Values of Crs were
      similar in black and white full-term infants (37.5 (SD 9.0) versus 35.0 (6.3)
      ml.kPa-1, respectively) suggesting that, in the immediate newborn period,
      separate reference values are not necessary for these parameters. However, Crs
      was somewhat lower in black than white preterm infants (26.0(5.2) versus
      29.5(7.2) ml.kPa-1, this difference reaching statistical significance if results
      were expressed in relation to body weight (95% confidence interval of within-pair
      differences -4.0 to -0.02 ml.kPa-1 x kg-1; p < 0.05). We conclude that no
      separate reference values for tidal breathing, Hering-Breuer reflex activity or
      total respiratory compliance are required for white and black babies in the
      immediate newborn period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143809
TI  - Bronchoalveolar lavage during neutropenic episodes: diagnostic yield and cellular
      pattern.
AB  - Few data are available concerning the relationship between alveolar and blood
      cell populations during neutropenia. We wanted to compare the value of pulmonary
      endoscopic procedures with lavage in neutropenic (polymorphonuclear (PMN) count <
      or = 1,000.mm-3) and non-neutropenic settings. We therefore, retrospectively,
      reviewed the results of 118 investigations for pneumonia in patients with
      malignant haematological diseases. All had bronchoalveolar lavage (BAL), and some
      had additional studies with protected bacteriological samples. Each BAL specimen
      was studied after cytocentrifugation by cytological examination for opportunistic
      infections, haemorrhage, virus, legionellae, and bacteriological cultures. The
      diagnostic yield of all endoscopic procedures (BAL, telescoping plugged catheter
      and protected specimen brush) was 53% in neutropenic (Group 1) and 61% in non
      neutropenic (Group 2) patients. The aetiological pattern of pneumonia was nearly
      the same in the two groups, except for more alveolar proteinosis in Group 1 and
      more cytomegalovirus (CMV) in Group 2. The absolute number of alveolar cells
      recovered through BAL (total number, macrophages, lymphocytes and PMNs) was
      significantly lower in neutropenic patients. We conclude that: 1) neutropenic
      patients with pneumonia require the same investigative approach as non
      neutropenic patients; 2) profound neutropenia may be concomitant with a decreased
      cellularity of alveoli, which may reflect the consequences of marrow aplasia on
      the pulmonary cell population and/or direct effect of chemotherapy on the lung.

PMID- 8143810
TI  - Altered bactericidal activity against Staphylococcus aureus in tuberculous
      bronchoalveolar lavage fluids.
AB  - We wished to evaluate the pulmonary defence capacity against common bacterial
      infections in patients with pulmonary tuberculosis. Bactericidal activity against
      Staphylococcus aureus of bronchoalveolar lavage fluids (cell-free supernatants)
      of patients with active (n = 13) and inactive pulmonary tuberculosis (n = 8), and
      normal individuals (n = 6), were studied. The 2 and 4 h bactericidal activities
      were higher than the 0 h activity in lavage fluids of healthy subjects and
      patients with inactive pulmonary tuberculosis. Active tuberculous lavage fluids
      were equally competent in their bactericidal activity against S. aureus at 0 and
      2 h, but a reduced S. aureus killing was seen at 4 h of incubation. Estimation of
      total phospholipid levels revealed no significant difference between the various
      lavage fluids. This reduced killing of S. aureus showed a relationship with the
      cellular components (lymphocytes and macrophages) of active tuberculous lavage
      fluids. A reduced killing was associated with no lymphocytic alveolitis, and an
      increased killing with lymphocytic alveolitis. This study suggests that alveolar
      lining material of patients with active pulmonary tuberculosis has less
      bactericidal activity against bacterial infections, such as S. aureus.

PMID- 8143811
TI  - Characterization of protein-antiproteinase imbalance in bronchoalveolar lavage
      from patients with pneumonia.
AB  - In order to clarify the mode of inactivation of alpha1-proteinase inhibitor
      (alpha 1-PI) in pneumonia, 21 immunocompetent patients and 19 immunocompromised
      patients with acute pneumonia (Groups I and II) were studied. Nine patients
      successfully treated for pneumonia and 10 healthy volunteers served as controls
      (Groups III and IV, respectively). The concentrations of alpha 1-PI, elastase and
      myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) were determined
      using a luminometric assay. Elastase inhibition capacity was determined using a
      colorimetric assay. Thus, the functional activity of alpha 1-PI was calculated.
      Both elastase and MPO were significantly higher in group I, when compared with
      the other groups. The mean concentration of alpha 1-PI was significantly higher
      in patients with acute pneumonia (Group I 13 mg.l-1, Group II 4.22 mg.l-1) than
      in Groups III and IV (2.65 and 0.33 mg.l-1, respectively), whereas, the
      proportion of active alpha 1-PI was significantly lower in Group I than in the
      other groups. Only a small proportion was present as a complex with elastase (ca.
      5.9%) or in oxidised form (ca. 4.8%), 85% of alpha 1-PI was irreversibly
      proteolyzed. This resulted in free elastase activity in 7 of the 40 patients
      (18%) with acute pneumonia. We conclude that functional activity of alpha 1-PI is
      markedly impaired due to irreversible proteolysis in acute pneumonia, despite
      high immunological concentrations.

PMID- 8143812
TI  - Lung cavitation associated with Pneumocystis carinii infection in the acquired
      immunodeficiency syndrome: a report of six cases and review of the literature.
AB  - Lung cavitation in patients with the acquired immune deficiency syndrome (AIDS)
      and Pneumocystis carinii pneumonia (PCP) has mainly been reported as single case
      studies. Among 160 episodes of PCP seen in a 1,000 bed teaching hospital and a
      600 bed teaching hospital from 1985-1992, we found six cases presenting with lung
      cavitation and documented Pneumocystis carinii infection. In the cases we report,
      as well as in the cases reviewed, cavities appear either alone or within an area
      of pulmonary consolidation, a mass or a nodule. They may present with
      haemoptysis, show unusual locations, and, most importantly, may frequently be
      misdiagnosed by bronchoalveolar lavage.

PMID- 8143813
TI  - Increased gamma/delta-positive T-cells in blood and bronchoalveolar lavage of
      patients with sarcoidosis and hypersensitivity pneumonitis.
AB  - A small population of T-cells does not express the conventional T-cell receptor
      (TCR), characterized by the alpha and beta polypeptide chains (alpha/beta TCR)
      but two polypeptides termed gamma and delta (gamma/delta TCR). Changes in
      gamma/delta TCR expression may be relevant as the cause or consequence of several
      diseases. Our study was undertaken to determine and compare the distribution of T
      cells expressing gamma/delta TCR in blood and bronchoalveolar lavage (BAL) of
      patients with sarcoidosis, hypersensitivity pneumonitis (HP), idiopathic
      pulmonary fibrosis (IPF), and of healthy controls. In addition, the association
      between gamma/delta TCR of blood T-lymphocytes and accessory molecules was
      analysed. Using direct immunofluorescence with the anti-gamma/delta TCR and anti
      CD3 monoclonal antibodies (MoAbs) followed by flow cytometric analysis, the blood
      of patients with pulmonary sarcoidosis, HP, IPF and of healthy controls was
      analysed. To reveal the association between gamma/delta TCR of blood T
      lymphocytes and the accessory molecules, expression of CD4, CD8 and CD25 were
      determined. Calculating the percentage and the total number of CD3+ gamma/delta
      TCR cells in blood, the data indicated a significant increase of gamma/delta T
      cells in individuals with pulmonary sarcoidosis and HP, compared to healthy
      controls and IPF patients. In sarcoidosis patients with elevated CD3+ gamma/delta
      TCR levels, significantly lower CD4/CD8 ratios were observed. In addition, our
      data demonstrate a correlation between the decrease of CD4+ cells in blood and
      the amplified appearance of gamma/delta TCR expression in sarcoidosis patients,
      but not in HP patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143814
TI  - Medical treatment of pulmonary hypertension in chronic lung disease.
AB  - In chronic respiratory diseases, especially chronic obstructive pulmonary disease
      (COPD) pulmonary arterial hypertension is generally mild to moderate and the
      necessity for treating it can, therefore, be questioned. In fact, pulmonary
      hypertension, even when modest, may worsen markedly during acute episodes,
      exercise and sleep. These acute increases in mean pulmonary artery pressure (PAP)
      could contribute to the development of right heart failure. Therefore, the
      medical treatment of pulmonary hypertension is justified. There are, at the
      present time, no selective pulmonary vasodilators, with the exception of inhaled
      nitric oxide. Indeed, vasodilators appear less effective in COPD compared to
      primary pulmonary hypertension. Thus, there is, at present, no justification for
      the long-term use of vasodilators in COPD patients. Long-term oxygen therapy
      (LTOT) attenuates and sometimes reverses the progression of pulmonary
      hypertension, although the condition rarely returns to normal. We do not know
      whether the structural changes of the pulmonary vasculature in COPD patients are
      potentially reversible with LTOT. The longer the daily duration of LTOT the
      better are the haemodynamic results. At present, LTOT remains the best treatment
      for pulmonary hypertension in COPD patient. In the future, treatment of this
      condition in COPD patients could combine LTOT and specific vasodilators.

PMID- 8143815
TI  - Definition and diagnosis of occupational asthma.
AB  - Asthma is the most frequent occupational lung disease. The diagnosis of
      occupational asthma, defined as variable airways narrowing, causally related to
      exposure in the working environment to specific airborne dusts, gases, vapours or
      fumes, needs to be confirmed by objective means. This article reviews the
      different steps of investigation which are: history, pulmonary function tests,
      immunological tests, monitoring of peak expiratory flows and nonallergic
      bronchial responsiveness and, finally, the gold standard, specific bronchial
      provocation.

PMID- 8143816
TI  - The epidemiology of occupational asthma.
AB  - With the accelerating pace of new knowledge about occupational asthma, systematic
      epidemiological approaches have yielded important new insights into its clinical
      characteristics. Such questions as "what proportion of all cases of asthma are
      caused by occupational exposures?" and "is occupational asthma incidence rising?"
      can now be answered. Surveillance programmes estimate the number of exposed
      individuals and the number of incident cases, allowing us to perceive the
      magnitude of the health problem. Although occupational asthma is a relatively
      common illness, very little is known about quantitative exposure-response
      relationships. Epidemiological techniques can quantify the importance of
      predisposing factors, such as atopy or cigarette smoking, in determining
      individual risk factors for occupational asthma. Still to be determined are the
      major, possibly genetic factors which make occupational asthma an "idiosyncratic"
      illness, affecting only a minority of those with equivalent exposures in the
      workplace. The goal of applying epidemiological techniques to the study of
      occupational asthma is ultimately to identify more effective means to prevent its
      occurrence.

PMID- 8143817
TI  - Aluminium potroom asthma: the Norwegian experience.
AB  - Work-related asthma in aluminium potroom workers, is reviewed and discussed,
      mainly on the basis of own investigations. The occurrence of work-related asthma
      has been shown to be associated with the duration of potroom employment, although
      the prevalence of asthmatic symptoms is not significantly different from that of
      the general population. Typical manifestations of occupational asthma are
      described in potroom workers, and a close relationship between the levels of
      fluoride exposure and work-related asthmatic symptoms has been observed. The
      existence of occupational asthma in aluminium potroom workers has been confirmed
      by characteristic patterns of repeated peak flow measurements, supported by
      changes in methacholine responsiveness in workers with suspected work-related
      asthma. However, no immunological test is available to establish the diagnosis.
      Methacholine challenge appears to be inappropriate for screening aluminium
      potroom workers in order to detect work-related asthma. Current smoking, but not
      self-reported allergy, is a risk factor for potroom asthma. A family history of
      asthma and previous occupational exposure may have some effect on the risk of
      developing symptoms. The prognosis of potroom asthma seems to depend on early
      replacement to unexposed work. The pathogenetic mechanisms are unknown, although
      some studies indirectly imply a hypersensitivity reaction. Future studies
      involving specific bronchial challenge appear to be necessary to find the causal
      agent(s) of aluminium potroom asthma.

PMID- 8143818
TI  - Breathing pattern, ventilatory drive and respiratory muscle strength in patients
      with chronic heart failure.
AB  - The purpose of this study was to evaluate whether chronic heart failure (CHF) may
      induce changes in breathing pattern and ventilatory neural drive. We studied 45
      male inpatients with CHF, (25 patients in NYHA class II, 20 in class III) and 22
      sex-matched post myocardial infarction patients without left ventricular
      dysfunction who served as controls. CHF patients underwent right heart
      catheterization and assessment of cardiac output by thermodilution technique.
      Patients and controls underwent evaluation of left ventricular ejection fraction
      by 2D echocardiography, spirometry, diffusion capacity, blood gases, breathing
      pattern, mouth occlusion pressure and respiratory muscle strength determination.
      Results of CHF patients were compared to controls and evaluated for differences
      according to the degree in severity of functional impairment. CHF patients showed
      a slight reduction in lung volumes and in diffusion capacity. In CHF neural
      drive, as assessed by mouth occlusion pressure (P0.1), was significantly
      increased in comparison to controls (P0.1 = 1.86 (0.7) and 1.4 (0.6) cmH2O in CHF
      and controls respectively). Analysis of breathing pattern showed only a slight
      yet significant increase in respiratory frequency while respiratory muscle
      strength, as assessed by measurement of maximal inspiratory and expiratory
      pressures (MIP and MEP respectively) was slightly reduced (MIP = 79(27) and
      104(28); MEP = 111(32) and 142(33) cmH2O respectively). Observed changes were
      more relevant in patients with advanced NYHA functional classes whereas no
      relationship among indices of cardiac and respiratory function was found. We
      conclude that chronic heart failure induces changes in neural ventilatory drive
      and respiratory muscle strength related to the severity of the disease.

PMID- 8143819
TI  - Exposure to environmental tobacco smoke and adult non-neoplastic respiratory
      diseases.
AB  - Exposure to environmental tobacco smoke (ETS) is widespread in European
      countries, the most serious exposures occurring at home and in the workplace.
      Epidemiological studies have, essentially, addressed the association between ETS
      exposure and respiratory health in children, and increased risk of lung cancer
      among adult nonsmokers. Relatively few studies have been reported on ETS and
      adult non-neoplastic respiratory diseases. On the basis of the available data, no
      definite conclusion (excluding the acute irritating effect of ETS on respiratory
      mucous membranes) can be drawn. Although biologically plausible, it remains
      controversial whether ETS exposure is associated with chronic respiratory
      symptoms and occurrence of chronic obstructive pulmonary disease, including
      asthma. Most of the studies that have used the most sensitive indicators of
      pulmonary function have suggested a negative impact of ETS exposure. However, if
      really present, the physiological significance of such small changes is unclear,
      and the relationship to long-term changes in lung function is not established.
      Moreover, the possibility of bias and confounding factors must be taken into
      account. Thus, there is a need for further epidemiological studies on ETS
      exposure and adult non-neoplastic respiratory disorders.

PMID- 8143821
TI  - Prevention of thermal and condensation errors in pneumotachographic recordings of
      the maximal forced expiratory manoeuvre.
AB  - When recording respiratory manoeuvres using a pneumotachograph (PT), it is
      customary to heat the pneumotachograph head to avoid condensation errors. It is
      technically demanding to heat the PT correctly, and this increases the complexity
      of the equipment. We have studied whether a simpler method can eradicate
      condensation errors and preserve thermal stability of the PT. We tested the
      accuracy of a PT by recording the discharge of 1,000 ml of air through the PT
      before and after a subject had blown through it, thus causing both condensation
      within the PT and a rise in its temperature. We then determined whether the
      thermal and condensation errors could be avoided by placing the PT, between
      blows, on a fan that was blowing air at a constant 1.65 l.s-1. With ambient
      temperature at 20 degrees C, a single blow through the PT was found to cause a
      subsequent 4% over-reading in volume, due to condensation and temperature changes
      in the PT. After five consecutive blows the error was 7%. Placing the PT on the
      fan for 15 s after a single blow abolished these errors, whereas a wait of 15 s
      did not. At an ambient temperature of 14 degrees C there was a 5% over-reading of
      volume after a single blow, and an over-reading of 9% after five blows. At an
      ambient temperature of 26 degrees C these errors were 3 and 5%, respectively. All
      of these errors were abolished by placing the PT on the fan for 15 s and 30 s,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143820
TI  - Serum tumour markers in lung cancer: history, biology and clinical applications.
AB  - The association of biological markers with cancer has been recognized for many
      decades. Current interest in markers for cancer arose in the mid 1960s, with the
      discoveries of alpha-fetoprotein and carcinoembryonic antigen. They were called
      oncofetal proteins, because of their presence in high concentrations during
      embryonic development, their virtual disappearance in the neonatal period, and
      their reappearance with cancers of specific cell types. Essentially, any
      molecular species may be produced in abnormal amounts or under abnormal
      circumstances by a tumour, and thereby become useful as a tumour marker. Several
      tumour markers have been studied in lung cancer. Unfortunately, none of these
      appear to be sufficiently sensitive and specific to be reliable for screening and
      diagnostic purposes. However, there is a body of evidence which proves that at
      least some of these substances may be useful in the evaluation of the course and
      prognosis of the disease. This review presents data concerning the most studied
      and interesting tumour markers in lung cancer.

PMID- 8143822
TI  - Respiratory effects of diving.

PMID- 8143823
TI  - A bronchial butterfly.
AB  - We report on an asthmatic patient who accidentally inhaled the small metal
      backing ("butterfly") of a nose stud, which she wore daily. Despite
      administration of nebulized salbutamol, postural drainage, and the use of rigid
      and fibreoptic bronchoscopes, attempted removal of the butterfly remained
      unsuccessful. Spontaneous expulsion of the butterfly occurred two months
      following inhalation. We suggest that consideration should be given by nose stud
      jewelry manufacturers to a more secure fixing device.

PMID- 8143824
TI  - Bochdalek hernia: a rare cause of pleural empyema.
AB  - This case report describes pleural empyema, caused by an intrathoracic ruptured
      stomach, in an adult patient with Bochdalek hernia. The possible complications
      and difficulties in diagnosing Bochdalek hernia in the adult are discussed.

PMID- 8143825
TI  - Lipoma of the external thoracic wall.
AB  - We report the case history of an external thoracic wall lipoma, which was noticed
      incidentally on a chest roentgenogram because of its calcification. A probable
      diagnosis was made by computer tomography. Because of the increase in size of the
      tumour it was removed surgically, but no evidence of malignant degeneration was
      found.

PMID- 8143826
TI  - Cystic pulmonary lesion in a 6 year old girl.

PMID- 8143827
TI  - Respiratory muscle function and exercise capacity in multiple sclerosis.
AB  - Patients with multiple sclerosis (MS) show a poor exercise tolerance. A reduction
      in respiratory muscle strength has also been reported. The purpose of this study
      was to evaluate whether reduction in exercise tolerance was related to
      respiratory muscle dysfunction. Twenty four multiple sclerosis patients (mean +/-
      SD age: 48 +/- 9 yrs, duration of illness 12.2 +/- 6 yrs, severity of illness as
      assessed by Expanded Disability Scale Score (EDSS) 5.3 +/- 2), underwent detailed
      evaluation of lung function tests, arterial blood gas analysis, respiratory
      muscle strength and endurance, and exercise test on an arm ergometer. Sixteen of
      the 24 patients were able to perform the exercise test (Group I), whilst the
      other eight were not (group II). Arterial blood gases and lung function tests
      were normal for both groups. Respiratory muscle strength as assessed both by
      maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) was
      significantly reduced (MIP 18-76 cmH2O; MEP 16-82 cmH2O) compared to predicted
      values. Inspiratory muscle endurance time was significantly reduced in Group II
      in comparison to Group I (247 +/- 148 vs 397 +/- 154 s, respectively). Both MIP
      and MEP were significantly related to inspiratory muscle endurance time.
      Endurance time, MIP and MEP were inversely significantly related to duration of
      illness, whilst only endurance time was significantly related to Expanded
      Disability Scale Score.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143828
TI  - Validity of ECSC prediction equations for spirometric indices in Dutch
      conscripts.
AB  - A study was performed to determine whether prediction equations issued by the
      European Community for Steel and Coal (ECSC) and the European Respiratory Society
      (ERS) fit spirometric data in young adult males. The study comprised 246 randomly
      selected Dutch conscripts, who participated in the study on the basis of informed
      consent. A questionnaire was used to assess respiratory symptoms and smoking
      habits. Maximal expiratory flow-volume curves were obtained with a rolling seal
      spirometer, and summary statistics selected according to ECSC/ERS
      recommendations. In addition, standing height and body weight were obtained. We
      analysed the data of 100 conscripts of European descent, with no history of
      respiratory symptoms. They were all life-long nonsmokers. Their mean (SD) age was
      18 (0.12) yrs (range 17.9-19.0 yrs), with a mean (SD) standing height of 1.84
      (0.06) m (range 1.68-2.00 m). The data for forced vital capacity (FVC), forced
      expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MMEF)
      agreed well with ECSC predictions; 95% confidence intervals (95% CI) of
      differences between measured and predicted values were -0.174 to 0.044 l, -0.012
      to 0.174 l.s-1 and -0.114 to 0.302 l.s-1, respectively. Peak expiratory flow was
      systematically larger than predicted, as was FEV1 % FVC (95% CI 0.74 to 1.31 l.s
      1 and 2.50 to 5.24%, respectively), due to the intercept being inappropriate. The
      residual standard deviation in the conscripts was somewhat less than in the
      ECSC/ERS predictions equations, except for peak expiratory flow (PEF).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143829
TI  - Respiratory health screening using pulmonary function tests and lung sound
      analysis.
AB  - Lung sounds (LS) analysis is a potential source of additional objective,
      noninvasive and quantitative information on the status of the pulmonary system.
      We have examined the hypothesis that the addition of lung sounds analysis to
      spirometry increases the sensitivity of objective population screening, as
      compared to the use of spirometry alone. Questionnaires, spirometry and lung
      sounds were obtained in 493 active workers. Lung sounds analysis consisted of the
      averaged power spectra of breath sounds, measured separately during inspiration
      and expiration at four standard locations over the trachea and the chest-wall. Of
      the 493 subjects, 91 had an obstructive lung disease, including 27 with chronic
      bronchitis identified by a history of prolonged cough and sputum production but
      with normal spirometry. Twelve additional workers had a restrictive lung disease.
      Abnormal spirometric results were found in 74 of the patients. Abnormal lung
      sounds analyses were found in 54 patients, including 14 of the chronic bronchitis
      cases, so that the overall sensitivity of objective screening tests increased
      from 71% to 87% by combining the two tests. Thirty three of the subjects
      considered normal by evaluation of their questionnaire and spirometry had
      abnormal lung sounds. Of the twenty four who were re-evaluated 12-18 months after
      the first tests, three had developed a lung or heart disease. We conclude that
      the combination of spirometry and lung sounds analysis significantly increased
      the sensitivity of detection of pulmonary diseases by objective tests, and
      provided an early sign of lung disease that was not detected by spirometry alone.

PMID- 8143830
TI  - Mechanisms of reduced pulmonary function after a saturation dive.
AB  - Deep saturation diving has been shown to have prolonged effects on pulmonary
      function. We wanted to assess the relative contribution of various factors that
      could contribute to these effects. Pulmonary function was, therefore, measured
      before and after 17 different saturation diving operations to depths of 5-450 m
      of sea water, corresponding to absolute pressures of 0.15-4.6 MPa. Four to
      fifteen divers participated in each operation. The measurements included static
      and dynamic lung volumes and flows, transfer factor of the lungs for carbon
      monoxide (TLCO), and closing volume. The dives were characterized by the
      cumulative hyperoxic and hyperbaric exposures, and the load of venous gas
      microemboli encountered during decompression was measured in 41 divers in three
      dives to 0.25, 1.2 and 3.7 MPa. TLCO was reduced by 8.3 +/- 7.0% mean +/- SD
      after the dives, this correlated with cumulative hyperoxic exposure and load of
      venous gas microembolism, independently of each other. Closing volume was
      increased and forced mid-expiratory flow rate reduced, in correlation with
      cumulative hyperoxic exposure. An increase in total lung capacity correlated with
      cumulative hyperbaric exposure. We conclude that hyperoxia, hyperbaria, and
      venous gas microembolism all contribute to the changes in pulmonary function
      after a single saturation dive, and all may explain some of the long-term effects
      of diving on pulmonary function.

PMID- 8143831
TI  - An exercise challenge protocol for epidemiological studies of asthma in children:
      comparison with histamine challenge.
AB  - We investigated whether an exercise challenge protocol is suitable for measuring
      bronchial responsiveness in epidemiological studies of asthma in children, and
      determined its comparability with histamine challenge. The exercise challenge was
      6 minutes of outdoor, free-range running at 85-90% of maximum heart rate,
      measured by heart rate monitor. Nose clips were worn. Distance run was measured
      to estimate oxygen consumption. Water content of the inspired air was < 10 mg
      H2O.l-1. Histamine challenge was by the rapid method. We used questionnaires to
      measure respiratory symptoms and skin prick tests to measure atopy. A total of 96
      children aged 8-11 years were studied. Bronchial hyperresponsiveness (BHR) to
      exercise challenge was defined as a fall in forced expiratory volume in one
      second (FEV1) of 13% of greater. Eleven children had a positive response to
      exercise challenge and 11 to histamine challenge but 12 responded to one
      challenge and not to the other. The correlation coefficient between the two tests
      was 0.65 (p = 0.0001). Exercise challenge thus proved to be a practical
      epidemiological tool for objective measurements of bronchial responsiveness in
      children. In this sample, some children responded to one challenge and not to the
      other which suggests that the two challenges identify different abnormalities of
      the airways.

PMID- 8143832
TI  - Refractoriness to inhaled sodium metabisulphite in subjects with mild asthma.
AB  - Refractoriness occurs after challenges causing mediator release in asthma, by a
      mechanism which may involve inhibitory prostaglandins. Bronchoconstriction due to
      inhaled sodium metabisulphite is thought to involve neural pathways and to be
      independent of mediator release; whether it shows refractoriness is uncertain. We
      have sought evidence of refractoriness to the bronchoconstrictor response to
      inhaled sodium metabisulphite in subjects with mild asthma, and have tested the
      hypothesis that the development of refractoriness involves inhibitory
      prostaglandins. Twelve subjects were challenged twice with a dose of sodium
      metabisulphite, previously shown to cause a 20% fall in forced expiratory volume
      in one second (FEV1); the second challenge proceeded after recovery from the
      first. The response to sodium metabisulphite was expressed as the maximum % fall
      in FEV1 and area under the change in FEV1 curve over 20 min (AUC). Nine subjects
      were studied after double-blind treatment with oral indomethacin, 50 mg t.d.s.,
      or placebo, for 3 days. The second sodium metabisulphite challenge caused
      significantly less bronchoconstriction than the first (mean maximum fall in FEV1
      13.1 and 24.3%, respectively). Nine subjects showed a greater than 50% reduction
      in the response to the second challenge (mean reduction in AUC 73.7%). In these
      subjects, indomethacin did not alter the response to the first sodium
      metabisulphite challenge, or the mean maximum fall in FEV1 in response to the
      second challenge (placebo 9.7%, indomethacin 11.2%), but significantly increased
      the AUC of the second challenge (placebo 55, indomethacin 114). The mean
      reduction in AUC from first to second challenge was 78% with placebo and 48% with
      indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143833
TI  - Quality of life, symptoms and pulmonary function in asthma: long-term treatment
      with nedocromil sodium examined in a controlled multicentre trial. Nedocromil
      Sodium Quality of Life Study Group.
AB  - This study was designed to measure improvement in quality of life of patients
      with asthma, using a standardized disease-specific questionnaire, the St George's
      Respiratory Questionnaire, in a year long double-blind, placebo-controlled, group
      comparative study with nedocromil sodium. Two other questionnaires were used: the
      Sickness Impact Profile (a measure of general health) and the Hospital Anxiety
      and Depression Scale. Measurements were made at baseline and following 24 and 48
      weeks of treatment. Response to therapy was also evaluated using daily diary card
      and peak flow measurements, clinic assessments and spirometry. Following a 4 week
      baseline, 719 adult asthmatics were randomized to treatment with 4 mg nedocromil
      sodium or placebo. Patients currently maintained on inhaled corticosteroids
      received treatments four times daily, those on bronchodilator alone received
      treatments twice daily. The Impacts component of the St George's Respiratory
      Questionnaire was significantly improved in patients receiving nedocromil sodium,
      as were night-time asthma, asthma severity at clinic, and daytime inhaled
      bronchodilator use. In patients receiving placebo, most of the traditional
      variables improved, and all three questionnaires recorded significant
      improvements in health. Patients and clinicians judged nedocromil sodium more
      effective than placebo. The improvement in St George's Questionnaire score in the
      nedocromil sodium treated patients was approximately double the change considered
      to be clinically significant. The study has shown that improvements in health
      with prophylactic therapy for asthma may be quantified by the use of a
      standardized disease-specific questionnaire.

PMID- 8143834
TI  - Lung deposition of budesonide inhaled via Turbuhaler: a comparison with
      terbutaline sulphate in normal subjects.
AB  - We wanted to evaluate whether lung deposition of budesonide and terbutaline
      sulphate differs, and to determine lung deposition of budesonide inhaled at
      different peak inspiratory flows, through Turbuhaler. Lung deposition of
      budesonide, a lipophilic substance, and of terbutaline sulphate, a hydrophilic
      substance, was therefore compared, after administration via an inspiratory flow
      driven, multi-dose, powder inhaler (Turbuhaler, Astra Draco AB) to 10 healthy
      volunteers. The radionuclide 99mTc was used to label drug particles, and
      radioactivity, indicating drug deposition, was measured using a gamma camera.
      Budesonide was inhaled at a normal flow of 58 l.min-1 and at a slow flow of 36 l
      min-1. At the faster flow, a mean +/- SD 27.7 +/- 9.5% of the metered dose was
      deposited in the lung and at the slower flow 14.8 +/- 3.3% was deposited (p <
      0.001). Mean lung deposition of terbutaline sulphate inhaled at 57 l.min-1 was
      27.0 +/- 7.7%. We conclude that inspiratory flow has an important effect on lung
      deposition, but water solubility appears to have no effect.

PMID- 8143835
TI  - Gamma-interferon modifies guinea pig airway functions in vitro.
AB  - Cytokines produced by T-lymphocytes may have significant roles in the airway
      inflammation seen in bronchial asthma. Gamma interferon (IFN-gamma), a T-cell
      derived cytokine, is known to modify functions of both immune and non-immune
      cells. In this study, we investigated whether IFN-gamma can modify guinea pig
      airway functions in vitro. The isometric tension of guinea pig airway strips was
      measured in a tissue bath filled with Krebs-Henseleit solution. Contracting
      responses to carbachol and KCl, and the relaxing response to isoproterenol (ISO)
      were examined. Effects of IFN-gamma were examined by comparing responses of the
      strips incubated with or without IFN-gamma (1000 U.ml-1; 25,000 U.ml-1).
      Contracting responses to carbachol and KCl were not affected by the incubation
      with IFN-gamma other than slight increased in maximum contraction by carbachol
      after 5 hours incubation with 25,000 U.ml-1 of IFN-gamma. Both 1 and 5 h
      incubation of strips with 25,000 U.ml-1 IFN-gamma significantly increased the
      sensitivity to ISO (p < 0.01 and p < 0.05, respectively) without affecting
      maximum relaxation. The effect of IFN-gamma on ISO relaxation was abolished by
      the denudation of airway epithelium from strips, indomethacin (2 microM), and
      cycloheximide (70 microM) but not by N omega-nitro-L-arginine methyl ester (30
      microM). In addition, heat-inactivated IFN-gamma and bacterial endotoxin (LPS,
      0.625 pg.ml-1) had no effect on ISO relaxation. These results suggest that IFN
      gamma is able to modify airway smooth muscle response to beta-adrenergic agonist
      by inducing release of prostanoids from airway epithelium.

PMID- 8143836
TI  - Mucolytic treatment with N-acetylcysteine L-lysinate metered dose inhaler in
      dogs: airway epithelial function changes.
AB  - N-acetylcysteine L-lysinate Nacystelyn (L-NAC) is a newly synthesized mucolytic
      agent, of which the action in vivo has not been well defined. In six healthy
      mongrel dogs, the rheological properties of mucus, its mucociliary and cough
      clearability, and the transepithelial potential difference (PD) of the
      tracheobronchial epithelium were evaluated after placebo and L-NAC metered dose
      inhaler (MDI) aerosols. The principal index of mucus rigidity, log G*, decreased
      at all airway sites with L-NAC administration, i.e. the mucus became less rigid
      and more deformable (the overall change in G* was 0.29 log units, i.e. ca.
      twofold decrease). The viscoelasticity-derived mucus transportability parameters,
      mucociliary (MCI) and cough (CCI) clearability indices, increased with L-NAC MDI,
      particularly CCI, which predicts the effect of mucus rheology on cough
      clearability. PD increased significantly with L-NAC administration at all
      measurement sites, which appears to be a novel effect for a direct acting
      mucolytic agent. Tracheal mucus linear velocity (TMV) increased after L-NAC
      compared with placebo, as did the normalized frog palate transport rate (NFPTR).
      The increase in NFPTR was greater than that predicted from the mucus rheological
      properties alone, suggesting that L-NAC still resident in the collected mucus
      stimulated the frog palate cilia. The index of mucus flux, the collection rate in
      mg.min-1, was higher with L-NAC compared with placebo. From our results, we
      conclude that L-NAC shows potential benefit in terms of improving mucus
      rheological properties and clearability. It may act, in part, by stimulating the
      fresh secretion of mucus of lower viscoelasticity. The stimulation of mucociliary
      clearance could be related to ion flux changes, as indicated by the increase in
      PD.

PMID- 8143837
TI  - A non-glycosylated form of pulmonary surfactant protein A appears in rat amniotic
      fluid.
AB  - Surfactant protein A (SP-A) is a family of glycoproteins that have a triplet with
      26, 32 and 36 kDa under reducing conditions in rat lung. We wanted to evaluate
      the SP-A forms in amniotic fluid of pregnant rats compared to those found in rat
      lungs. By Western blot analysis, glycosylated SP-A, was not found in the amniotic
      fluid in contrast to the pulmonary surfactant triplet SP-A, which comprises a 26
      kDa protein and its glycosylated 32 and 36 kDa forms. The SP-A concentration in
      amniotic fluid was barely detectable at 18 days of gestation (20 +/- 12 ng.ml-1),
      and then increased and reached 700 +/- 333 ng.ml-1 at the final gestational day
      21, as determined by an enzyme-linked immunoabsorbent assay.
      Immunohistochemically, SP-A was found in some epithelial cells of larger
      respiratory bronchi, but not, or to a lesser degree, in smaller respiratory
      bronchi at gestational day 18. At 21 days of gestation, SP-A was detected in
      bronchial and bronchiolar nonciliated epithelial Clara cells, alveolar epithelial
      type II cells and some alveolar macrophages. The ratio of the 26, 32 and 36 kDa
      SP-A forms in bronchoalveolar, bronchobronchiolar and tracheal lavage fluids
      prepared from adult rats was 6:29:65, 84:5:11 and 100:0:0, respectively. These
      findings show the presence of a non-glycosylated SP-A in rat amniotic fluid. This
      may reflect the increased ratio of non-glycosylated SP-A to bronchoalveolar,
      bronchobronchiolar and tracheal lavage fluids, respectively.

PMID- 8143838
TI  - The intrabronchial microbial flora in chronic bronchitis patients: a target for N
      acetylcysteine therapy?
AB  - Chronic bronchitis is common among smokers, often together with recurrent
      infectious exacerbations. Streptococcus pneumoniae and Haemophilus influenzae are
      the pathogens traditionally considered most important. N-acetylcysteine (NAC)
      treatment has been shown to reduce the number of infectious exacerbations in
      patients with chronic bronchitis. The mechanism behind this is unknown. We
      attempted to characterize the intrabronchial bacterial flora in patients with
      chronic bronchitis in an infection-free interval, and to determine whether
      pharmacological and immunological factors effected the bacterial occurrence.
      Twenty two smokers with non-obstructive chronic bronchitis, 19 smokers with
      chronic bronchitis and chronic obstructive pulmonary disease (COPD) and 14
      healthy nonsmokers underwent bronchoscopy. To obtain uncontaminated
      intrabronchial samples, a protected specimen brush was used. Quantitative
      bacterial cultures and virus isolations were performed. Significantly positive
      bacterial cultures (> 1,000 colony-forming units (cfu).ml-1) were found only in
      the patients. S. pneumoniae and H. influenzae were found in five patients, and
      only in the patients without NAC treatment. The most common bacterium was alpha
      haemolytic streptococcus. Negative cultures were more common in the healthy
      controls. Of the various factors examined, only NAC medication had an influence
      on bacterial numbers. Significantly fewer patients with NAC medication had
      positive cultures (3 out of 16) than in the group of patients without NAC therapy
      (15 out of 21). Our results confirm that chronic bronchitis in smokers leads to
      increased intrabronchial bacterial colonization. We could also confirm that 1,000
      cfu.ml-1 is an adequate cut-off level for significant bacterial growth when using
      the protected specimen brush. NAC medication was associated with low bacterial
      numbers.

PMID- 8143839
TI  - Rapid validation of molecular structures of biological samples by electrospray
      mass spectrometry.
AB  - A short account is presented of the method of measuring molecular masses (M(r))
      of pure biological samples by electrospray ionisation mass spectrometry. It is
      demonstrated that the technique yields M(r) values with an effective accuracy
      equal to or better than 0.008% of the calculated M(r), provided that the correct
      molecular structure is employed in the calculation. It is therefore recommended
      that this method of measuring M(r)'s should be considered to form an essential
      part of all studies aimed at elucidating the molecular structure of purified
      biological macromolecules or for confirming the identity of labelled samples of
      such molecules.

PMID- 8143840
TI  - An endothelin B receptor-selective antagonist: IRL 1038, [Cys11- Cys15]
      endothelin-1(11-21)

PMID- 8143841
TI  - Three-dimensional crystal structure of recombinant erabutoxin a at 2.0 A
      resolution.
AB  - Recombinant erabutoxin a (Ea(r)) has been crystallized by vapour diffusion in
      hanging drops. The crystals belong to space group P2(1)2(1)2(1) with cell
      dimensions a = 55.8 A, b = 53.4 A, c = 40.8 A. Diffraction data have been
      recorded on a FAST detector up to 2.0 A. The atomic crystal structure of Ea(r)
      has been determined by initial refinement of the structure of the isotoxin
      erabutoxin b (Eb) the crystals of which were grown under identical conditions.
      The R-factor was 23% at 2.0 A resolution. The secondary and tertiary structures
      of Ea(r) are shown to be identical with that of wild-type Eb, within the
      experimental error.

PMID- 8143842
TI  - Fc gamma receptor II stimulated formation of inositol phosphates in human
      platelets is blocked by tyrosine kinase inhibitors and associated with tyrosine
      phosphorylation of the receptor.
AB  - We report that activation of phospholipase C (PLC) by cross-linking of the
      platelet low-affinity Fc gamma receptor II (Fc gamma RII) is inhibited by two
      structurally distinct tyrosine kinase inhibitors, staurosporine and ST271. This
      contrasts with PLC activation induced by thrombin and U46619, a thromboxane
      mimetic, whose receptors have seven transmembrane domains characteristic of G
      protein coupled receptors. Several proteins undergo phosphorylation on tyrosine
      on Fc gamma RII cross-linking upstream of protein kinase C (PKC), Ca2+ and
      aggregation, including the Fc gamma RII itself. The role of Fc gamma RII
      phosphorylation in the regulation of PLC is discussed.

PMID- 8143843
TI  - Expression of alpha-1,3 linkage-containing oligomannosyl residues in a cell-wall
      mannan of Candida tropicalis grown in yeast extract-Sabouraud liquid medium under
      acidic conditions.
AB  - We investigated the cell-wall mannan obtained from Candida tropicalis IFO 1647
      strain cells grown in yeast extract-Sabouraud medium at pH 3.0 by two-dimensional
      homonuclear Hartmann-Hahn spectroscopy. The results indicate that the phosphate
      group and the side chains containing a beta-1,2-linked mannopyranose unit
      decreased compared to those of mannan from cells grown under conventional
      conditions (pH 5.9) with concomitant expression of alpha-1,3 linkage-containing
      oligomannosyl side chains. The results of acetolysis of these mannans indicated
      that the presence of alpha-1,3-linked mannopyranose unit existed in side chains
      corresponding to pentaose and hexaose, Manp alpha 1-3 Manp alpha 1-2Manp alpha 1
      2 Manp alpha 1-2Man, and Manp alpha 1-2Manp alpha 1-3Manp alpha 1-2Manp alpha 1
      2Manp alpha 1-2Man, in the mannan from cells grown at pH 3.0.

PMID- 8143844
TI  - Dual pertussis toxin-sensitive pathway of zymosan-induced activation in guinea
      pig macrophages. An anti-CR3 antibody-inhibitable stimulation of phagocytosis and
      -resistant stimulation of O2- production and arachidonate release.
AB  - Complement receptor type 3 (CR3)-mediated cellular responses in guinea pig
      macrophages were investigated by using zymosan and serum-opsonized zymosan (SOZ)
      as the multivalent ligand for CR3. The ingestion of zymosan and SOZ was
      accompanied by O2- generation and arachidonate release. These responses were
      suppressed by prior exposure of macrophages to pertussis toxin (PT). Opsonization
      of zymosan gave rise to more than 6-fold activation of the ingestion, whereas the
      magnitude of either arachidonate release or O2- generation was unchanged. The
      Fab' fragment of anti-Z-1, a monoclonal antibody specific for the alpha chain of
      guinea pig CR3, inhibited the ingestion of zymosan by 60% without affecting
      zymosan-induced arachidonate release and O2- generation. These data suggested
      that there might be at least two functionally distinct binding sites for zymosan.
      O2- generation and arachidonate release might be regulated through one site and
      phagocytosis another. Both sites should be coupled to PT-sensitive GTP binding
      protein.

PMID- 8143845
TI  - Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or
      aspirin acetylation of this residue stimulates 15-R-HETE synthesis.
AB  - Prostaglandin G/H synthase (PGHS) is a key enzyme in cellular prostaglandin (PG)
      synthesis and is the target of non-steroidal anti-inflammatory agents. PGHS
      occurs in two isoforms, termed PGHS-1 and PGHS-2. These isoforms differ in
      several respects, including their enzymatic activity following acetylation by
      aspirin. While PG synthesis by both isoforms is inhibited by aspirin, 15-R
      hydroxyeicosatetraenoic acid (15-R-HETE) synthesis by PGHS-2, but not PGHS-1, is
      stimulated by preincubation with aspirin. We have mutated the putative aspirin
      acetylation site of hPGHS-2, and expressed the mutants in COS-7 cells using
      recombinant vaccinia virus. Enzyme activity and inhibitor sensitivity studies
      provide evidence that Ser516 is the aspirin acetylation site of human PGHS-2 and
      that substitution of a methionine residue at this position can mimic the effects
      of aspirin acetylation on enzyme activity.

PMID- 8143846
TI  - Tyrosine-194 of glycogenin undergoes autocatalytic glucosylation but is not
      essential for catalytic function and activity.
AB  - Glycogenin is the protein primer for glycogen synthesis. By autocatalytic
      transglucosylation from UDPglucose, it creates a malto-octaose chain attached to
      its Tyr-194. It has been uncertain whether the autocatalysis includes the
      addition of the first glucose residue to Tyr-194. We now show this to be the
      case. However, we also demonstrate, contrary to a claim by others, that Tyr-194
      is not necessary for the catalytic function and activity of glycogenin.

PMID- 8143847
TI  - In vitro binding of the two-finger repressor CreA to several consensus and non
      consensus sites at the ipnA upstream region is context dependent.
AB  - The two zinc-fingers of the Aspergillus nidulans repressor CreA recognize the
      consensus hexanucleotide 5'-SYGGRG-3'. We have determined all the CreA binding
      sites in a approximately 2 kb region upstream the ipnA gene. Our analysis shows
      that (i) CreA binds to certain consensus sites in a context-dependent manner;
      (ii) five non-consensus 6-bp sequences are also recognized by CreA; this non
      canonical binding correlates with the presence of a second, neighbouring CreA
      binding site, suggesting that recognition of two linked sites stabilizes CreA
      binding. Our results suggest that the binding possibilities of CreA might be more
      complex than originally envisaged.

PMID- 8143848
TI  - Peroxynitrite releases copper from caeruloplasmin: implications for
      atherosclerosis.
AB  - Peroxynitrite may be formed in the vasculature by the reaction of superoxide with
      nitric oxide. When the blue copper-containing protein, caeruloplasmin, is
      incubated with peroxynitrite, copper is released, and ferroxidase activity and
      the blue colouration are lost. When plasma from normal subjects is incubated with
      peroxynitrite, the oxidant reacts with numerous plasma constituents but is still
      able to release copper from caeruloplasmin. As the ferroxidase activity of
      caeruloplasmin is lost in plasma in the presence of peroxynitrite, a second
      ferroxidase activity associated with peroxidised lipids, and not inhibited by
      azide, is formed.

PMID- 8143849
TI  - Purification and characterization of a ubenimex (Bestatin)-sensitive
      aminopeptidase B-like enzyme from K562 human chronic myeloid leukemia cells.
AB  - A ubenimex-sensitive aminopeptidase B-like enzyme was purified from the non
      membrane-bound fraction of K562 cells by a series of chromatographic procedures
      and slab-gel electrophoresis. The apparent molecular mass of the enzyme was
      estimated to be 73 kDa by SDS-PAGE. The aminopeptidase activity was activated by
      chloride ions and inhibited by Zn2+, Cu2+, Cd2+, and p-chloromercuribenzoic acid.
      Ubenimex was a potent inhibitor of this aminopeptidase in the nanomolar range.
      The sequence of the N-terminus of the protein was not determined. Partial amino
      acid sequencing revealed that the N-terminus of this aminopeptidase B-like enzyme
      was blocked by acylation. The partial sequences of the two fragments produced by
      CNBr cleavage and an acylamino acid-releasing reaction showed this enzyme to be a
      new aminopeptidase.

PMID- 8143850
TI  - Alteration of the specificity of ecotin, an E. coli serine proteinase inhibitor,
      by site directed mutagenesis.
AB  - The gene of ecotin, an E. coli proteinase inhibitor, was cloned, and by site
      directed mutagenesis the active site residue of the protein, Met84, was mutated
      to Lys, Arg and Leu. The recombinant wild-type and mutant inhibitors were
      overexpressed in E. coli, purified to homogeneity and their inhibitory effects on
      trypsin, chymotrypsin and elastase were compared. Of these serine proteinases
      trypsin is the most strongly inhibited by wild type ecotin and its mutants.
      According to our results the character of residue 84 of ecotin significantly but
      not dramatically modifies the specificity of the inhibitor.

PMID- 8143851
TI  - Localization of an arginine-specific mono-ADP-ribosyltransferase in skeletal
      muscle sarcolemma and transverse tubules.
AB  - The precise localization of a membrane-bound, arginine-specific mono-ADP
      ribosyltransferase (mADP-RT) was assessed in rabbit skeletal muscle by studying
      membrane fractions isolated by successive sucrose density gradient
      centrifugations. mADP-RT activity was 10-fold enriched in sarcolemmal and T
      tubular membranes. The catalytic activity, determined in preparations with mainly
      right-side-out vesicles, was found to be on the cytoplasmic face. As revealed by
      SDS-PAGE and autoradiography endogenous mADP-RT activity labeled several proteins
      in the range between 15 kDa and 250 kDa. T-tubules contained the highest number
      of [32P]ADP-ribose-labeled proteins.

PMID- 8143852
TI  - Two hypotheses--one answer. Sequence comparison does not support an evolutionary
      link between halobacterial retinal proteins including bacteriorhodopsin and
      eukaryotic G-protein-coupled receptors.
AB  - The structure of bacteriorhodopsin (BR) of Halobacterium halobium is known.
      Despite the lack of sequence similarities it is often taken as a model for
      eukaryotic G-protein-coupled receptors (GPCRs). Recently two hypotheses were used
      to support the homology of BR and GPCRs, namely evolution by exon shuffling and
      evolution by gene duplication. BR is a member of a family of halobacterial
      retinal proteins. The sequences of eight members of this family were used to test
      the two hypotheses. Based on sequence comparison, no indication for an
      evolutionary linkage between the two protein families could be found.

PMID- 8143853
TI  - Regulatory sequences required for hst-1 expression in embryonal carcinoma cells.
AB  - The hst-1 gene, which is implicated in mammalian embryonic development and
      morphological transformation of NIH3T3 cells, is expressed in undifferentiated F9
      cells, but not in differentiated F9 and other well-differentiated cells, such as
      PYS-2, NIH3T3 and HeLa cells. An octamer element present in the 3' untranslated
      region acts as an enhancer. Although Oct3 is down-regulated when F9 cells are
      differentiated, transient expression of Oct3 did not enhance the hst-1 promoter
      activity in HeLa, NIH3T3 or PYS-2 cells. Thus, the role of Oct3 on hst-1
      expression remains elusive, and an additional transcription factor which
      interacts may regulate hst-1 transcription in association with Oct1, Oct3 or
      both.

PMID- 8143854
TI  - Expression of protein kinase C isoforms in smooth muscle cells in various states
      of differentiation.
AB  - We analysed the expression of protein kinase C (PKC) isoforms in smooth muscle
      cells (SMC) in various states of differentiation, using Western blots and
      thermocycle amplification of mRNA. SMC isolated from intact tissues express three
      isoforms of PKC, namely alpha, delta, and zeta. Following cell culture, SMC
      additionally express mRNA for PKC-epsilon, but significant amounts of the
      corresponding protein were not detected. Transformed SMC, such as the cell line
      DDT1 MF-2, express both mRNA and protein for PKC-epsilon, lack the delta
      isoenzyme, whilst maintaining the expression of the alpha and zeta isoforms. Thus
      PKC-delta and epsilon isoenzyme expression appears to vary with the state of
      differentiation of these cells, with PKC-epsilon expression increasing as the
      cells become proliferative.

PMID- 8143855
TI  - Mutation of a putative ADP-ribosylation motif in the Pasteurella multocida toxin
      does not affect mitogenic activity.
AB  - Pasteurella multocida toxin (PMT) is a potent mitogen for Swiss 3T3 fibroblasts
      and cytotoxic to embryonic bovine lung cells. Site-directed mutagenesis was used
      to investigate the functional significance of a three amino acid motif in PMT
      that is present in five other bacterial protein toxins which exhibit ADP-ribosyl
      transferase activity. Crude lysates of mutant clones were fully cytotoxic for
      embryonic bovine lung cells. Purified mutant toxin was also as effective at
      stimulating inositol phosphate turnover and nucleic acid synthesis as wild type
      toxin. We conclude that this motif has no functional significance in Pasteurella
      multocida toxin.

PMID- 8143856
TI  - Cloning and functional characterization of the human 5-HT2B serotonin receptor.
AB  - Recently, we have reported the cloning of the rat 5-HT2B receptor cDNA. This
      receptor is particularly interesting since it may be involved in diseases such as
      migraine. Here, we describe the isolation of a human 5-HT2B receptor clone from a
      cDNA library derived from SH-SY5Y cells. Although the receptor sequence was only
      80% homologous to the rat sequence, the exon-intron distribution was conserved
      between the two species. In the human body, the receptor mRNA was detected in
      most peripheral organs. Only low expression levels were found in the brain. After
      expression in HEK 293 cells, activation of the receptor stimulated the production
      of phosphatidylinositol. The pharmacology of this functional response correlated
      well with that of the rodent receptor.

PMID- 8143857
TI  - Lactosylceramide is synthesized in the lumen of the Golgi apparatus.
AB  - Recently, synthesis of lactosylceramide has been described to occur on the
      cytosolic face of the Golgi [(1991) J. Biol. Chem. 266, 20907-20912]. The
      reactions following in the biosynthesis of higher glycosphingolipids are known to
      take place in the lumen of the Golgi. For our understanding of the functional
      organization of the multiglycosyltransferase system of glycosphingolipid
      synthesis in the Golgi, the knowledge of the topology of individual reactions is
      a prerequisite. We have developed a simple and quick assay system for
      sphingolipid biosynthesis and have obtained evidence that lactosylceramide is
      synthesized in the lumen of the Golgi. Because lactosylceramide is generated by
      galactosylation of glucosylceramide which, in turn, is synthesized from ceramide
      and UDP-Glc on the cytosolic surface of the Golgi apparatus, further efforts will
      be directed to the characterization of a glucosylceramide-translator in the Golgi
      membranes rather than a lactosylceramide-translocator.

PMID- 8143858
TI  - Cloning and expression of the vesamicol binding protein from the marine ray
      Torpedo. Homology with the putative vesicular acetylcholine transporter UNC-17
      from Caenorhabditis elegans.
AB  - Complementary DNA clones corresponding to a messenger RNA encoding a 56 kDa
      polypeptide have been obtained from Torpedo marmorata and Torpedo ocellata
      electric lobe libraries, by homology screening with a probe obtained from the
      putative acetylcholine transporter from the nematode Caenorhabditis elegans. The
      Torpedo proteins display approximately 50% overall identity to the C. elegans unc
      17 protein and 43% identity to the two vesicle monoamine transporters (VMAT1 and
      VMAT2). This family of proteins is highly conserved within 12 domains which
      potentially span the vesicle membrane, with little similarity within the putative
      intraluminal glycosylated loop and at the N- and C-termini. The approximately 3.0
      kb mRNA species is specifically expressed in the brain and highly enriched in the
      electric lobe of Torpedo. The Torpedo protein, expressed in CV-1 fibroblast
      cells, possesses a high-affinity binding site for vesamicol (Kd = 6 nM), a drug
      which blocks in vitro and in vivo acetylcholine accumulation in cholinergic
      vesicles.

PMID- 8143859
TI  - Synthetic melanin and ferric ions promote superoxide anion-mediated lipid
      peroxidation.
AB  - In this study, we demonstrate that synthetic dopa-melanin produced superoxide
      anions and promoted the peroxidative cleavage of phospholipids in the presence of
      Fe(3+)-ADP complexes. SOD significantly suppressed this lipid peroxidation, while
      catalase or sodium benzoate did not. During the reaction, MCLA-dependent
      chemiluminescence was detected, and this was suppressed to the control level by
      the addition of SOD. Melanin has been postulated to be toxic to tissues because
      of its interaction with redox-active paramagnetic metal ions, and these findings
      suggest that superoxide anion-mediated lipid peroxidation is induced by melanin
      in the presence of iron.

PMID- 8143860
TI  - A comparison of demethoxyviridin and wortmannin as inhibitors of
      phosphatidylinositol 3-kinase.
AB  - The mammalian Ptdlns 3-kinase is shown to be inhibited by low nanomolar
      concentrations of demethoxyviridin, an antifungal agent structurally related to
      wortmannin. The inhibitory potency of both compounds could be observed in
      purified Ptdlns 3-kinase whether or not the regulatory subunit (p85 alpha) was
      present, suggesting that the inhibitors bind to the catalytic subunit (p110) of
      the Ptdlns 3-kinase. These inhibitors also show similar potency against the
      intrinsic p85-phosphorylating activity of the p110-kinase. However, the
      structurally related Ptdlns 3-kinase from Saccharomyces cerevisiae (Vps34p) is
      not inhibited by either compound. Both inhibitors target the mammalian Ptdlns 3
      kinase in vitro and in vivo, implying that these compounds should be useful in
      suppressing Ptdlns 3-kinase in mammalian systems. The inhibitors did not affect
      the mammalian Ptdlns 4-kinase, but they are able to inhibit a membrane-associated
      Ptdlns 4-kinase from Schizosaccharomyces pombe.

PMID- 8143861
TI  - Differential response of NF-kappa B1 p105 and NF-kappa B2 p100 to HTLV-I encoded
      Tax.
AB  - In a previous study we found that HTLV-I encoded Tax transactivator, which binds
      to NF-kappa B1 p105, suppresses p105-mediated I kappa B activity, thereby
      allowing entry of NF-kappa B p65 (RelA) and p50 into the nucleus. In the present
      report, we compared the effect of Tax on NF-kappa B2 p100, which also binds to
      Tax, with that of p105 in transfected COS7 cells. While p105 is processed to the
      DNA binding form, p50, processing of p100 was much less efficient both in the
      presence and absence of Tax. Both p105 and p100 showed I kappa B activity in
      sequestering NF-kappa B p65 into the cytoplasm. However, only p105-mediated I
      kappa B activity, and not that of p100, was inhibited by Tax. Chimeric molecules
      between p100 and p105 suggested that inefficient processing of p100 can be
      attributed to the Rel homologous domain, rather than to the ankyrin repeat
      domain. p100, but not p105, potently suppressed Tax- and p65-induced transaction
      of a GM-CSF promoter in Jurkat cells. Taken together, these results suggest that
      p105 and p100 may have distinct effects on Tax-induced transactivation events.

PMID- 8143862
TI  - Regulation of the cloned L-type cardiac calcium channel by cyclic-AMP-dependent
      protein kinase.
AB  - Hormones can regulate cardiac L-type Ca2+ channels via cAMP-dependent protein
      kinase (PKA) phosphorylation. However, regulation of the cloned L-type Ca2+
      channel has been difficult to demonstrate conclusively. We stably transfected a
      human embryonic kidney (HEK-293) cell with the cardiac alpha 1 and beta 2
      subunits, then examined PKA modulation of the Ca2+ current. Although forskolin
      did not increase basal Ca2+ current, the PKA inhibitors, H-89 and Rp-cAMPS, could
      inhibit basal current. We reversed H-89 inhibition with either forskolin or
      okadaic acid. We conclude that the channel was phosphorylated under basal
      conditions, and that inhibition of PKA allowed dephosphorylation. These studies
      demonstrate that reversible PKA regulation of cloned Ca2+ channels can be studied
      in HEK-293 cells.

PMID- 8143863
TI  - Molecular cloning of rat JAK3, a novel member of the JAK family of protein
      tyrosine kinases.
AB  - We have cloned and sequenced a cDNA (JAK3) encoding a novel member of the JAK
      family of protein tyrosine kinases. JAK3 was identified by RT-PCR of rat
      mesangial cells using degenerate oligonucleotide primers, and a full-length clone
      was isolated from a rat spleen cDNA library. The primary structure of JAK3 showed
      cDNA with an open reading frame of 1,100 amino acids which comprises the PTK
      catalytic domain and a second kinase-related domain characteristic for JAK
      kinase. JAK3 was phylogenetically shown to be most closely related to JAK2 among
      the previously known JAK family members, JAK1, JAK2 and Tyk2. Southern analysis
      revealed that JAK3 is a single copy gene and well conserved in the vertebral
      genome. Northern analysis indicated that the 4.0 kb mRNA was transcribed in a
      variety of tissues including spleen, lung, kidney and intestine.

PMID- 8143864
TI  - Restoration of normal ultrastructure after expression of the alpha 1 subunit of
      the L-type Ca2+ channel in dysgenic myotubes.
AB  - Muscular dysgenesis (mdg) is a spontaneous mutation affecting the alpha 1 subunit
      of the skeletal L-type Ca2+ channel. mdg/mdg mice suffer from a skeletal muscle
      disease characterised by low levels of the slow Ca2+ current, lack of contractile
      activity, and immature organisation of skeletal muscle. Microinjections of a cDNA
      encoding alpha 1 into mutant myotubes restore excitation-contraction coupling. We
      checked here that dysgenic myotubes transfected with expression vectors,
      including a full-length alpha 1 cDNA, also recover normal ultrastructural
      features. Transfection of alpha 1 cDNA partially deleted on the 5' end leads to
      the recovery of a good structural organisation without any improvement in the
      mutant physiological phenotype. These results suggest that: (i) the proper
      expression of alpha 1 is required for the full muscle differentiation of muscular
      dysgenesis myotubes, and (ii) portions of the alpha 1 molecule may be involved in
      the structural organisation of a muscle fiber, independent of its known
      functional properties.

PMID- 8143865
TI  - W-7, a calmodulin antagonist, primes the stimulation of human neutrophil
      respiratory burst by formyl peptides and platelet-activating factor.
AB  - Low concentrations of the calmodulin antagonist W-7 (1-10 microM) enhanced the
      respiratory burst (RB) of human polymorphonuclear leukocytes (PMN) stimulated by
      N-formyl-methionyl-leucyl-phenylalanine, whereas high drug concentrations (above
      20 microM) depressed it. The maximal increase obtained with 5-10 microM W-7
      affected both initial rate (50%) and total superoxide anion production (150%). W
      7 also primed both parameters of the RB mediated by platelet-activating factor,
      although higher drug concentrations were required (15-50 microM). By contrast, W
      7 depressed the RB induced by the calcium ionophore A23187 and by a protein
      kinase C activator, phorbol myristate acetate, with an IC50 of approximately 20
      and 8 microM, respectively. These data show the enhancing effect of W-7 on
      chemoattractant-mediated RB and suggest that RB priming may involve calmodulin
      dependent regulation of chemoattractant-mediated early signalling events.

PMID- 8143866
TI  - Purification and characterisation of dRP-A: a single-stranded DNA binding protein
      from Drosophila melanogaster.
AB  - Replication protein A (RP-A) is an essential single-stranded DNA binding protein
      (SSB) involved in the initiation and elongation phases of eukaryotic DNA
      replication. It has the ability to bind single-stranded DNA extremely tightly and
      possesses a characteristic hetero-trimeric structure. Here we present a method
      for the purification of RP-A from Drosophila melanogaster embryos. Drosophila RP
      A (dRP-A) has subunits of about 66, 31 and 8 kDa, in line with analogues from
      other species. It binds single-stranded DNA very tightly via the large subunit.
      The complete protein has at least a 10- to 20-fold preference for single-stranded
      DNA over double-stranded DNA and it appears that binding is only weakly co
      operative. Band shift experiments suggest that it has an approximate site
      covering the size of 16 nucleotides or less, however, it shows a greater affinity
      for long oligonucleotides than for short ones. We also demonstrate that dRP-A can
      stimulate the activity of its homologous DNA polymerase alpha in excess of 20
      fold. Analysis of the protein's abundance during embryo development indicates
      that it varies in a manner akin to other replication proteins.

PMID- 8143867
TI  - Changing root system architecture through inhibition of putrescine and feruloyl
      putrescine accumulation.
AB  - Plant roots provide anchorage and absorb the water and minerals necessary for
      photosynthesis in the aerial parts of the plant. Since plants are sessile
      organisms, their root systems must forage for resources in heterogeneous soils
      through differential branching and elongation [(1988) Funct. Ecol. 2, 345-351;
      (1991) Plant Roots: The Hidden Half, pp. 3-25, Marcel Dekker, NY]. Adaptation to
      drought, for instance, can be facilitated by increased root growth and
      penetration. Root systems thus develop as a function of environmental variables
      and the needs of the plant [(1988) Funct. Ecol. 2, 345-351; (1986) Bot. Gaz. 147,
      137-147; (1991) Plant Roots: The Hidden Half, pp. 309-330, Marcel Dekker, NY]. We
      show, in a model system consisting of excised tobacco roots, that both alpha-DL
      difluoromethylornithine (an inhibitor of putrescine biosynthesis) and the rolA
      gene (from the root-inducing transferred DNA of Agrobacterium rhizogenes)
      stimulate overall root growth and cause a conversion in the pattern of root
      system formation, producing a dominant or 'tap' root. These morphological changes
      are correlated with a depression in the accumulation of polyamines and their
      conjugates.

PMID- 8143868
TI  - Phospholipase D activation in fibroblast membranes by the alpha and beta isoforms
      of protein kinase C.
AB  - The regulation of phosphatidylcholine-hydrolyzing phospholipase D (PLD) by
      protein kinase C (PRC) in membranes of Chinese hamster lung fibroblasts (CCL39)
      was studied using conventional PKC isoforms alpha, beta and gamma isolated from
      rat brain and recombinant PKC isoforms. Cells were incubated with [14C]choline to
      label endogenous phosphatidylcholine before membranes were prepared and assayed
      for release of [14C]choline. PKC alpha was the most potent activator of PLD,
      producing a maximal effect at approximately 0.1 microgram/ml. PKC beta also
      stimulated PLD but was less potent and less efficacious, whereas PKC gamma was
      ineffective. Stimulation required addition of a PKC activator, but the isoform
      specificity was the same whether phorbol 12-myristate 13-acetate (PMA) or Ca2+
      was used. Recombinant Ca(2+)-independent PKC isoforms delta, epsilon, and zeta
      failed to stimulate PLD, but recombinant PKC beta 1 stimulated PLD in a manner
      similar to the purified brain PKC beta. Immunoblot analysis of the soluble
      fraction of CCL 39 fibroblasts detected only the alpha and zeta isoforms of PKC.
      The results suggest that PKC alpha and beta are activators of PLD and that PKC
      alpha is responsible for the activation in these fibroblasts.

PMID- 8143869
TI  - Crystal structure of momordin, a type I ribosome inactivating protein from the
      seeds of Momordica charantia.
AB  - A type I ribosome-inactivating protein, extracted and purified from M. charantia
      seeds, was crystallised by vapour diffusion with polyethylene glycol at pH 7.2. X
      ray data were collected to 2.1 A resolution and the structure solved by molecular
      replacement using the A-chain coordinates of ricin. The overall fold of the
      protein is similar to ricin but there are differences in secondary structure, on
      the surface and in the active site cleft. These differences are probably due in
      part to the evolution of the protein without a B-chain partner. The most
      extensive reorganisation occurs at the C-terminus whereas Tyr70 shows the
      greatest change in the active site cleft.

PMID- 8143870
TI  - Evidence for Rap1 in vascular smooth muscle cells. Regulation of their expression
      by platelet-derived growth factor BB.
AB  - The effect of platelet-derived growth factor (PDGF) on Rap1 expression was
      investigated in rat vascular smooth muscle cells (SMC). First, evidence for Rap1
      proteins was shown by their: (i) detection in membranes using a specific anti
      Rap1 antibody, (ii) typical shift in electrophoretic mobility as a consequence of
      reduction, and (iii) cAMP-induced phosphorylation and immunoprecipitation. Then,
      the mitogenic activity of 10 ng/ml PDGF AA and BB for 48 h, resulting in a 2- and
      5-fold increase in [3H]thymidine incorporation, was correlated with that of total
      Rap1 protein expression which was found to be 99% +/- 36% and 260% +/- 70%,
      respectively. Further time-course studies established that this up-regulation of
      Rap1 proteins was only observed after 48 h of PDGF BB treatment. Lastly,
      comparative RT-PCR of both rap1a and rap1b mRNAs showed that PDGF BB also up
      regulated the rap1a mRNA species, which was 1.5-fold increased in contrast with
      the rap1b mRNA species. It is concluded that the PDGF BB-induced SMC
      proliferation is associated with an up-regulation of Rap1a protein.

PMID- 8143872
TI  - Oxidation of LDL by nitric oxide and its modification by superoxides in
      macrophage and cell-free systems.
AB  - Oxidative modification of low density lipoproteins (LDL) can increase the
      atherogenicity of LDL. Here we demonstrate the potential role of nitric oxide
      (NO) in LDL modification. Dose-dependent alterations of LDL including an increase
      in electrophoretic mobility, generation of peroxides and degradation of
      apoprotein B occurred during incubation with NO. Sodium nitroprusside was also
      shown to increase the electromobility of LDL. Superoxide dismutase (SOD) and
      catalase did not affect this result. NO treatment also increases the negative
      charges on other lipoproteins. In addition, we have demonstrated that NO plays a
      protective role in macrophage or superoxide-induced LDL modification through its
      neutralizing action.

PMID- 8143871
TI  - The expression of PDGF-alpha but not PDGF-beta receptors is suppressed in
      Swiss/3T3 fibroblasts over-expressing protein kinase C-alpha.
AB  - The generation and characterization of Swiss/3T3 cells which stably over-express
      protein kinase C (PKC)-alpha were previously described by us. In these cells over
      expression of PKC-alpha reduced the expression of epidermal growth factor (EGF)
      receptor molecules [(1990) J. Biol. Chem. 265, 13290-13296]. Here we show that
      the expression of PDGF-alpha receptors, but not PDGF-beta receptors, was
      specifically decreased in these cells. Not only were the levels of PDGF-alpha
      receptor mRNA transcript and protein significantly diminished in the PKC-alpha
      over-producing cells, but their ability to respond to short- and long-term growth
      factor signals was appropriately compromised. This was reflected in a reduced
      tyrosine autophosphorylation signal in response to PDGF-AA, as well as in
      decreased growth rates of PKC-alpha over-expressing cells when supplied with
      external PDGF-AA. A similar decrease in PDGF-alpha receptors was also
      demonstrated in parental Swiss/3T3 cells treated with phorbol esters. Our studies
      imply that PKC-alpha is involved in a cellular mechanism suppressing the
      expression of PDGF-alpha receptors in Swiss/3T3 cells. Hence, activation of PKC
      alpha or alterations in its cellular levels may affect, in turn, the expression
      of a specific set of cell surface receptors and their responses to external
      growth factors.

PMID- 8143873
TI  - Localization of phospholipid-binding sites of caldesmon.
AB  - The interaction of phosphatidylserine with intact smooth muscle caldesmon and
      caldesmon fragments obtained by bacterial expression was investigated by means of
      light scattering. Among these fragments only those derived from the C-terminal
      part of caldesmon (so-called domain 4) were able to interact with phospholipids.
      Fragments 606C (residues 606-756), H7 (566-710) and H2 (626-710) form tight
      complexes with phosphatidylserine, whereas fragments H8 (658-737), H9 (669-737)
      and fragment H4 (566-624) interact with phospholipids less effectively. It is
      concluded that the phospholipid-binding site is located in the sequence 626-710
      of caldesmon. This sequence contains calmodulin-binding sites and serine residues
      phosphorylated by protein kinase C and pro-directed protein kinases. This could
      explain the effects of calmodulin and phosphorylation on the caldesmon
      phospholipid interaction described earlier.

PMID- 8143874
TI  - Biochemical, pharmacological and genomic characterisation of Ts IV, an alpha
      toxin from the venom of the South American scorpion Tityus serrulatus.
AB  - The venom of the scorpion, Tityus serrulatus, was fractionated to investigate the
      chemical and pharmacological properties of its alpha-toxin content. Three alpha
      toxins (Ts III, Ts IV and Ts V) were purified by conventional chromatography (gel
      filtration and ion-exchange chromatography), followed by immunoaffinity
      chromatography. Competition experiments using reference alpha- and beta-toxins
      suggested that these alpha-toxins were contaminated with around 0.01% of beta
      toxin. The sequence of the first 30 amino acids of Ts IV was established. Using
      an oligonucleotide probe, a cDNA encoding its precursor was cloned from a venom
      gland cDNA library. The primary structure deduced from the cDNA nucleotide
      sequence provides possible explanations for the polymorphism of these three
      molecules.

PMID- 8143875
TI  - Biochemical properties of attachment region binding protein ARBP.
AB  - ARBP (attachment region binding protein) is an abundant nuclear protein that
      specifically binds to matrix/scaffold attachment regions (MARs/SARs). Here we
      show by gel filtration and gradient sedimentation that ARBP has an elongated
      shape. The sedimentation coefficient was determined as only 2.1 S. Furthermore,
      limited proteolysis of ARBP in situ (in isolated nuclei) with several proteases
      generated limiting resistant peptides from 14.5 to 18 kDa, that retained the
      ability to bind MARs specifically. This indicates that these peptides encompass
      the DNA binding domain of ARBP.

PMID- 8143876
TI  - Achievement of renaturation of subtilisin BPN' by a novel procedure using organic
      salts and a digestible mutant of Streptomyces subtilisin inhibitor.
AB  - The pro-sequences of proteases have been considered to be required for the
      refolding of denatured proteases. However, here we report achievement of almost
      complete restoration of enzymatic activity of subtilisin BPN' in the absence of
      its pro-sequence. The presence of 2 M potassium acetate in the folding medium
      enhanced the refolding efficiency of guanidine hydrochloride (GdnHCl)-denatured
      subtilisin BPN' by up to 28%, and other organic salts were also found to be
      useful, suggesting that general contribution of the bulky hydrophobic moieties of
      the salts to the formation of a favorable environment required for folding. This
      finding will provide new insights into the folding mechanisms not only of
      proteases but also of various other proteins. Almost complete restoration of
      enzymatic activity of denatured subtilisin in the organic salt solution was
      accomplished by further addition of mutated Streptomyces subtilisin inhibitor
      (SSI), which had been converted to a digestible temporary inhibitor by removal of
      the disulfide bridge near the reactive site.

PMID- 8143877
TI  - The actin binding site in the tail domain of Dictyostelium myosin IC (myoC)
      resides within the glycine- and proline-rich sequence (tail homology region 2).
AB  - The majority of protozoan myosins I possess tail domains composed of three
      distinct and conserved regions of sequence, referred to as tail homology regions
      1, 2 and 3 (TH.1, TH.2 and TH.3). While the N-terminal approximately half of the
      tail (corresponding to TH.1) has been implicated in membrane binding, all or some
      portion of the C-terminal approximately half of the tail (corresponding to TH.2
      plus TH.3) has been implicated in binding to F-actin in a nucleotide-insensitive
      fashion. Here we show, using fusion proteins containing portions of the
      Dictyostelium myosin IC (myoC) tail domain and F-actin sedimentation assays, that
      the ability of the myoC tail to bind to actin resides entirely within the glycine
      and proline-rich TH.2 domain. The src-like TH.3 domain does not bind to actin,
      nor does it augment the binding properties of the TH.2 domain. In addition to
      defining more precisely the location of the actin binding site in the tail domain
      of a protozoan myosin I, these results have implications for the function of the
      src-like TH.3 domain in myosins I and other proteins.

PMID- 8143878
TI  - Identification of the 23 kDa subunit of tau protein kinase II as a putative
      activator of cdk5 in bovine brain.
AB  - Tau protein kinase II (TPKII) was reported previously to be composed of a neuron
      rich cdc2-related kinase (PSSALRE/cdk5) and 23 kDa subunit. Here we show that the
      23 kDa subunit is a putative activator for the kinase activity. Amino acid
      sequence analysis revealed that the protein was novel and included a partial
      similarity of amino acids to a cyclin box important for the interaction with cdc2
      related kinase. These results suggest that the 23 kDa subunit, but not cyclin,
      activates cdk5 in neuronal cells, which no longer exhibit cell cycling but are
      terminally differentiated cells.

PMID- 8143879
TI  - Cardiac L-type Ca2+ channel triggers transmitter release in PC12 cells.
AB  - Among the various voltage-sensitive Ca2+ channels present in PC12 cells are the
      dihydropyridine (DHP)-sensitive L-channel, the omega-conotoxin (omega-CgTx)
      sensitive N-channel, and an atypical omega-CgTx/DHP-insensitive Ca2+ channel.
      Depolarization-evoked Ca2+ entry and [3H]dopamine release is mediated by L-type
      Ca2+ channels determined by the use of Ca2+ channel antagonists, and a single
      protein of 250 kDa is recognized by L-type-specific antibodies. Screening of a
      PC12 cDNA library revealed two types of Ca2+ channels which were identified by
      partial sequencing. A pc12-L clone displayed virtually identical sequence
      homology to the cardiac L-type channel. The identical sequence homology of the
      single alternative splicing region confirmed clone pc12-L as the rbC-I
      transcript, a cardiac-neuronal alpha 1 subunit expressed in rat brain. Clone pc12
      N displayed identical sequence homology to rbB-I, a neuronal alpha 1 subunit of
      the N-type Ca2+ channel expressed in rat brain; Northern blot analysis identified
      RNA of a size similar to that previously described for rat brain.

PMID- 8143880
TI  - An isoform of the human calcitonin receptor is expressed in TT cells and in
      medullary carcinoma of the thyroid.
AB  - We amplified, using the polymerase chain reaction and calcitonin receptor (CTR)
      specific primers, RNA extracted from medullary thyroid carcinoma (MTC) and the
      derived TT cell line. Both secrete large amounts of calcitonin. Electrophoresis
      of amplification products revealed, in both cases, an ethidium bromide-stained
      band that hybridized to a CTR probe. Sequencing the band amplified from TT cells
      revealed an open reading frame identical to the sequence of H-CTR but lacking 16
      amino acids in the first intracellular loop. This demonstrates the existence of
      an mRNA coding for a subtype of H-CTR which is expressed in TT cells and MTC.

PMID- 8143881
TI  - Identification of axial ligands of cytochrome c552 from Nitrosomonas europaea.
AB  - Cytochrome c552 from Nitrosomonas europaea was analyzed by visible, EPR and MCD
      spectroscopies. The visible and MCD data show that histidine and methionine are
      the axial ligands to the heme iron of the ferric protein. The EPR spectrum of the
      cytochrome shows an atypical highly axial low spin (HALS) type signal with g
      values that make it difficult to identify the axial ligands. These results
      reinforce the value of near-infrared MCD spectroscopy for assigning ligands in
      ferric heme systems and point out the difficulties in using only EPR spectroscopy
      for the same purpose. The description of another c-cytochrome exhibiting a HALS
      type EPR signal will eventually be helpful in explaining the physical basis for
      this unusual signal.

PMID- 8143882
TI  - Purification, inhibitory properties, amino acid sequence and identification of
      the reactive site of a new serine proteinase inhibitor from oil-rape (Brassica
      napus) seed.
AB  - A new serine proteinase inhibitor, rapeseed trypsin inhibitor (RTI), has been
      isolated from rapeseed (Brassica napus var. oleifera) seed. The protein inhibits
      the catalytic activity of bovine beta-trypsin and bovine alpha-chymotrypsin with
      apparent dissociation constants of 3.0 x 10(-10) M and 4.1 x 10(-7) M, at pH 8.0
      and 21 degrees C, respectively. The stoichiometry of both proteinase-inhibitor
      complexes is 1:1. The amino acid sequence of RTI consists of 60 amino acid
      residues, corresponding to an M(r) of about 6.7 kDa. The P1-P1' reactive site
      bond has been tentatively identified at position Arg20-Ile21. RTI shows no
      similarity to other serine proteinase inhibitors except the low molecular weight
      mustard trypsin inhibitor (MTI-2). RTI and MTI-2 could be members of a new class
      of plant serine proteinase inhibitors.

PMID- 8143883
TI  - [Knowledge about and attitude to HIV/AIDS among dentists and dental assistants in
      Budapest, November 1992].
AB  - 118 Dentists and 115 Dental Nurses opinion was evaluated about their knowledges
      and attitudes to HIV/AIDS problem in Budapest (Hungary) 1992 November. The
      frequency of false knowledges about the transmission was 5-10%. More than 70% of
      the asked persons changed their habits in working place and 62% of dentists and
      78% of nurses uses rubber gloves. 2.5% of the dentists and 7.8% of nurses thinks
      they will refuse the treatment of a HIV/AIDS patient. Most informations collected
      the doctors from professional literature and the nurses from mass medias, the
      mention of postgraduate trainings was low. Above data are valid for those persons
      who are working in the state health care system. Data of the private practice
      will be collected and analysed in the future.

PMID- 8143884
TI  - [Dental status of 14-18-year old secondary school students in Budapest (VIII.
      District) in 1991. (Implications of a dental-sociological study)].
AB  - In this dento-sociological examination the dental status of 1623 secondary-school
      students living in the capital of Hungary, was found better than that of the same
      aged students examined previously. The number of decayed teeth was higher than
      the number of filled teeth. The average level of oral hygiene was found between
      "good" and "middle" levels. Among the three types of secondary schools the best
      oral hygiene status was found in the secondary grammar school.

PMID- 8143885
TI  - Possible mechanisms of alteration in the capacities of carcinogen metabolizing
      enzymes during schistosomiasis and their role in bladder cancer induction.
AB  - Carcinoma of the urinary bladder is the most common malignancy in many tropical
      and subtropical countries. There is a well documented association with chronic
      urinary schistosomal infection, and bladder cancer associated with
      schistosomiasis is a major cause of morbidity and mortality in the endemic areas.
      Many factors have been suggested as possible causative agents in schistosome
      associated bladder carcinogenesis but theories concerning the possible role of
      schistosomal infection in altering host metabolism of chemical carcinogens have
      received most attention. In experimental schistosomiasis there is a common
      pattern of changes in the activities of several hepatic Phase I and Phase II
      enzymes. Phase I enzymes show increased activities in the early stages of
      infection but these activities are reduced to below their preinfection levels in
      the intermediate and late chronic stages of the disease. The activities of Phase
      II enzymes are altered in favour of the deconjugation pathways in the later
      stages of the disease. The possible basic mechanisms that might be involved in
      such changes during parasitism and their potential role in the induction of
      bladder neoplasia are discussed.

PMID- 8143886
TI  - Pilot controlled double-blind study of the hypnotic effects of zolpidem in
      patients with chronic 'learned' insomnia: psychometric and polysomnographic
      evaluation.
AB  - In a pilot double-blind trial in 21 patients with learned or idiopathic insomnia
      (DSM-IIIR), patients received placebo for 1 week (nights 1-7), either active
      (zolpidem, 10 mg) or placebo treatment for 2 weeks (nights 8-21) and then placebo
      for a further week (nights 22-28). Variables to measure efficacy, rebound and
      withdrawal were assessed daily from day 1 to day 28. Polysomnographic recordings
      together with sleep cycle analysis were performed on nights 7, 21 and 28.
      Patients treated with 10 mg zolpidem for 2 weeks had significantly improved sleep
      efficiency at the end of the randomised double-blind phase compared with the
      placebo group. Fractionated sleep-cycle analysis showed an increase in slow-wave
      sleep during the first 2-hour cycle after sleep onset. During the withdrawal
      placebo week, most of the main sleep variables remained relatively stable in the
      zolpidem group (nights 22-28), and deteriorated further in the placebo group. At
      the end of the withdrawal phase, there was a statistically significant difference
      between groups, in favour of the zolpidem treatment, in sleep efficiency, total
      sleep time, absolute and percentage of time awake, and percentage of REM sleep.
      REM sleep, which was normal in both groups at baseline, decreased significantly
      in the placebo group between nights 22 and 28 (during the withdrawal placebo
      week) compared with the zolpidem treatment group, and the number of periods of
      time awake increased. Minor subjective complaints were recorded under zolpidem
      and were comparable with those under placebo. Zolpidem seemed to improve some
      important sleep variables, when assessed both objectively and subjectively. The
      sleep cycle analysis suggested a possible shift of slow-wave sleep to an earlier
      period of the night, with a more physiological sleep structure. There was no
      evidence for withdrawal or rebound after stopping the 2 weeks of zolpidem
      treatment, but rather signs that the effect of zolpidem outlasted active
      treatment. The present pilot study justifies a prospective confirmatory
      comparison of zolpidem with benzodiazepines in an adequate number of patients and
      withdrawal after 6-8 weeks of treatment.

PMID- 8143887
TI  - Effects of tropisetron, a 5-hydroxytryptamine type 3 receptor blocker, on
      intestinal secretion induced by cholera toxin or deoxycholic acid in rabbits in
      vivo.
AB  - It has been suggested that 5-hydroxytryptamine is involved in the pathogenesis of
      various intestinal hypersecretory states including cholera. In this study, the
      effect of tropisetron (ICS 205-930), a specific 5-hydroxytryptamine type-3
      receptor blocker, on jejunal and colonic fluid secretion induced respectively by
      cholera toxin and deoxycholic acid was investigated in rabbits using isolated
      loops of intestine in vivo. Marked fluid accumulation in both the jejunal and
      colonic loops was observed after exposure to cholera toxin and deoxycholic acid
      respectively. Elevation of jejunal and colonic mucosal cyclic adenosine
      monophosphate concentrations was also noted. Intraperitoneal administration of
      tropisetron dose-dependent inhibited jejunal secretion induced by cholera toxin.
      In contrast, no significant anti-secretory effect of tropisetron was observed
      against colonic secretion induced by deoxycholic acid. Tropisetron did not affect
      elevated mucosal cyclic adenosine monophosphate concentrations. The inhibitory
      effect of tropisetron on intestinal secretion induced by cholera toxin, which was
      independent of cyclic adenosine monophosphate formation, suggests that 5
      hydroxytryptamine plays an important role in this type of secretion.

PMID- 8143888
TI  - Accumulation of new quinolones in the blood of elderly patients.
AB  - The correlation between serum levels of five new quinolones (norfloxacin,
      ofloxacin, enoxacin, ciprofloxacin and lomefloxacin), age and 24 h creatinine
      clearance was studied in 180 patients. One of five new quinolones was orally
      administered, before transurethral resection of the prostate, at the dosage of
      200 mg three times daily for 3 consecutive days. Serum levels were checked 5.5 h
      or about 17 h after the final administration. Creatinine clearance was found to
      be negatively correlated with aging (P < 0.001). After oral administration, the
      level of certain accumulated new quinolones in serum increased with the age of
      patients (P < 0.001-0.1). This tendency was more marked for ofloxacin,
      lomefloxacin and enoxacin than for ciprofloxacin and norfloxacin. The
      investigators concluded that the level of accumulated new quinolones in serum
      with aging is correlated to the 24 h urinary excretion rate of each new
      quinolone. These results indicate that ofloxacin, lomefloxacin and enoxacin,
      which have higher 24 h urinary excretion rates, should be administered at lower
      doses according to the age of the patient, in order to prevent adverse reactions.

PMID- 8143889
TI  - Interactions between glucocorticoids and mineralocorticoids in the regulation of
      renal electrolyte transport.
AB  - The enzyme 11 beta-hydroxy steroid dehydrogenase (11 beta-OHSD) was described and
      its location in various organs noted more than 30 years ago (Mahesh and Ulrich,
      1960; Jenkins, 1966). 11 beta-OHSD inactivates circulating glucocorticoids by
      transforming the hydroxyl group at the 11-carbon to a keto group. This chemical
      reaction has taken on a greater degree of physiologic and clinical significance
      in recent years. It has been suggested that 11 beta-OHSD, present in
      mineralocorticoid target tissues, can act as a 'guardian' over the
      mineralocorticoid receptor by transforming circulating endogenous glucocorticoids
      to their respective 'biologically inert' 11-dehydro derivatives (Edwards et al.,
      1988; Funder et al., 1988). These derivatives do not bind to mineralocorticoid
      receptors (MR) while both their parent compounds and mineralocorticoids bind to
      cloned MR with equal affinity (Arriza et al., 1987). 11 beta-OHSD has generated a
      growing sense of scientific excitement since this enzyme may represent one of a
      family of metabolic pathways or mechanisms which can regulate steroid induced
      renal reabsorption of sodium. Such 'protective' enzymatic pathways, present in
      the kidney and elsewhere, may not only control the access of glucocorticoids to
      MR, but control the access of glucocorticoids to glucocorticoid receptors (GR)
      (Teelucksingh et al., 1990; Monder, 1990) as well as access of mineralocorticoids
      to their own receptors. This review will focus on this concept of a family of
      protective enzymatic pathways and the possible physiological implications.

PMID- 8143890
TI  - Exon-specific northern analysis and rapid amplification of cDNA ends (RACE)
      reveal that the proximal promoter II (PII) is responsible for aromatase
      cytochrome P450 (CYP19) expression in human ovary.
AB  - Estrogens are synthesized from C19 steroids by a unique form of cytochrome P450,
      aromatase cytochrome P-450 (P-450AROM; the product of the CYP19 gene). We have
      shown that tissue-specific expression of human P-450AROM is determined, in part,
      by the use of alternative promoters. Previous methods of analysis for determining
      the specific 5'-termini of the different transcripts included S1 nuclease
      protection, primer extension, and Northern analysis. In the present study we have
      used the RACE procedure (rapid amplification of cDNA ends) to amplify and clone
      the 5' termini of P-450AROM transcripts expressed in human corpus luteum (CL).
      Sequencing of the resulting clones supports the results of the previously
      performed studies. Specifically, the proximal promoter, PII, is the predominant
      promoter utilized in CL, such that the start of transcription occurs 26 bp
      downstream of the putative TATA sequence. A minority of the clones possess an
      alternative 5'-end, namely I.3. Exon-specific Northern analysis confirms that the
      majority of the P-450AROM transcripts in CL tissue contain sequence specific for
      promoter II. Similarly, exon-specific Northern analysis indicates that
      transcripts in human follicles, as well as granulosa cells in culture, contain
      primarily sequence specific for promoter II.

PMID- 8143891
TI  - Steroidogenic enzyme activity after acute activation of protein kinase (PK) A and
      PKC in ovine small and large luteal cells.
AB  - Intracellular effector systems which utilize PKA and PKC can be pharmacologically
      activated by forskolin and phorbol 12-myristate 13-acetate (PMA) and appear to be
      important for regulation of steroidogenesis by cells of the corpus luteum. In
      this study the effect of pharmacologic activation of PKA (forskolin) or PKC (PMA)
      on the activity of adenylate cyclase, cholesterol esterase, P450 cholesterol side
      chain cleavage (P450scc) and 3 beta-hydroxysteroid dehydrogenase/delta 5, delta 4
      isomerase (3 beta HSD) was determined. Basal adenylate cyclase activity (as
      measured by intracellular and secreted cAMP) was extremely low in both large and
      small luteal cells. Forskolin stimulated adenylate cyclase activity in both large
      and small luteal cells but progesterone production was increased only in small
      cells. PMA inhibited progesterone production by large and forskolin-stimulated
      small cells without altering adenylate cyclase activity. Basal cholesterol
      esterase activity was greater in small than in large cells and was stimulated by
      forskolin only in small cells. PMA did not significantly alter cholesterol
      esterase activity in either cell type. Activity of P450scc or 3 beta HSD was
      measured by conversion of hydroxylated cholesterol derivatives (P450scc) or
      pregnenolone (3 beta HSD) to progesterone. Although basal progesterone production
      was 47 times greater in large than small cells, there was only 5.1 (P450scc) and
      6.4 (3 beta HSD) times greater enzyme activity in large than in small luteal
      cells. Activation of PKA and/or PKC did not alter the activity of P450scc or 3
      beta HSD in either cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143892
TI  - Basic fibroblast growth factor-induced increase in 125I-human chorionic
      gonadotropin binding to luteinizing hormone receptors in cultured immature Leydig
      cells is mediated by binding to heparan sulfate proteoglycans.
AB  - Previous studies have shown that basic fibroblast growth (bFGF) has a biphasic
      effect on 125I-hCG binding to LH receptors in cultured Leydig cells from immature
      rats. Low concentrations of bFGF (0.1-1.0 ng/ml) progressively decreased binding,
      while higher concentrations (10-100 ng/ml) progressively increased binding above
      nadir levels. In the present studies, treatment of cultured immature Leydig cells
      with heparinase I and/or heparinase III, which enzymatically remove heparan
      sulfate proteoglycans, had no effect on basal binding of 125I-hCG to LH receptors
      or the decrease in binding due to treatment with low bFGF concentrations;
      however, this treatment dramatically reduced the secondary increase in binding
      following the addition of higher bFGF concentrations. These results strongly
      support the idea that the secondary increase in 125I-hCG binding to LH receptors
      elicited by treatment with higher bFGF concentrations is mediated by bFGF binding
      to heparan sulfate proteoglycans associated with the plasma membrane and/or
      extracellular matrix.

PMID- 8143893
TI  - Regulation of the levels of three transforming growth factor beta mRNAs by
      estrogen and their effects on the proliferation of human breast cancer cells.
AB  - Transforming growth factor (TGF) beta is a potent regulator of cell proliferation
      and may play a role in breast cancer cell growth. We have evaluated the
      regulation of TGF beta 1, TGF beta 2, and TGF beta 3 mRNAs by 17 beta-estradiol
      (E2) and 4-hydroxytamoxifen (MOH) in estrogen receptor-positive (ER(+)) MCF-7 and
      estrogen receptor-negative (ER(-)) MDA-MB-231 human breast cancer cells. We also
      determined the effect of TGF beta 1, TGF beta 2, and TGF beta 3 on the
      proliferation of these cells. Cells were deprived of estrogen before the addition
      of hormones, and mRNA was measured by Northern blot analysis. We found that MCF-7
      cells expressed mRNAs of all three TGF beta species. Treatment of MCF-7 cells
      with 10(-10) M E2 for 7 days resulted in a dramatic decrease in the TGF beta 2
      and TGF beta 3 mRNA levels, but not in the TGF beta 1 mRNA level. MOH was found
      to block these effects. In addition, the regulation of TGF beta 2 and beta 3 gene
      expression occurs at both transcriptional and post-transcriptional levels. There
      is an inverse correlation between E2-induced growth and levels of TGF beta 2 and
      TGF beta 3 mRNA. In contrast to MCF-7 cells, MDA-MB-231 cells expressed TGF beta
      1 and TGF beta 2 mRNAs but TGF beta 3 mRNA was not detected, and the TGF beta 1
      and TGF beta 2 mRNAs were not regulated by estrogens or antiestrogens.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143894
TI  - Discrete stimulatory effects of platelet-derived growth factor (PDGF-BB) on
      Leydig cell steroidogenesis.
AB  - The effect of platelet-derived growth factor-BB on adult rat Leydig cell
      steroidogenesis has been determined using culture conditions which maintain
      testosterone production and responsiveness to luteinising hormone for 3 days. A
      significant stimulation of testosterone levels was observed in acute response to
      a maximally stimulating dose (8 ng/ml) of rat luteinising hormone on the third
      day of culture, but was dependent on pre-exposure of the Leydig cells to PDGF-BB
      for 2 days, whilst maintained in the presence of a minimum dose (0.1 ng/ml) of
      rat luteinising hormone. These data demonstrate a very discrete action of PDGF-BB
      on adult rat Leydig cell steroidogenesis in vitro, but whether or not this
      constitutes a significant paracrine effect in vivo remains to be established.

PMID- 8143895
TI  - Site-directed mutagenesis of hGH at the 54-74 loop selectively modifies its
      lactogenic receptor-mediated biological activity.
AB  - Four analogues of human growth hormone (hGH) mutated by site-directed mutagenesis
      at the 54-74 loop-Met-hGH(P59A), Met-hGH(P61A), Met-hGH(P59A,P61A) and Met
      hGH(Des 62-67) were analyzed for: (1) their biological activity mediated through
      lactogenic receptors using rat lymphoma Nb2-11C cell proliferation and mouse
      mammary gland HC-11 cell beta-casein synthesis bioassays and (2) their ability to
      interact with recombinant hGH binding protein (hGHBP). The analogues Met
      hGH(P59A), Met-hGH(P61A) and Met-hGH(P59A,P61A) partially lost their activity
      relative to native hGH in the HC-11, but not in the Nb2-11C cell bioassay. These
      analogues were nevertheless capable of forming a 1:2 complex with a recombinant
      hGH binding protein (hGHBP), despite the fact that the affinity of Met-hGH(P61A)
      and Met-hGH(P59A,P61A) analogues had decreased 8- and 14-fold, respectively. Met
      hGH(Des 62-67) failed to form 1:1 or 1:2 complexes with hGHBP and did not compete
      with [125I]hGH for binding to hGHBP. It lost all biological activity in HC-11
      cells, but retained 0.4% of its activity, in the Nb2-11C cell proliferation
      bioassay. These results confirm the involvement of Pro-61 in the hGH binding and
      activity mediated through somatogenic receptors, while the activity mediated
      through two different types of lactogenic receptors was selectively modified.
      These findings emphasize the fact that lactogen receptors in different species or
      organs are not identical.

PMID- 8143896
TI  - Temporal and spatial localization of steroidogenic enzymes in premenopausal human
      ovaries: in situ hybridization and immunohistochemical study.
AB  - In situ hybridization and immunohistochemical localization of cytochrome P450
      cholesterol side-chain cleavage (P450scc), 3 beta-hydroxysteroid dehydrogenase (3
      beta HSD), cytochrome P450 17 alpha-hydroxylase (P450c17) and cytochrome P450
      aromatase (P450arom) was performed in 50 morphologically normal human
      premenopausal ovaries, and correlated these findings with their endometrial
      phase. In general, mRNA expression of these enzymes examined by in situ
      hybridization were in good agreement with immunolocalization examined by
      immunohistochemistry. Expression of P450scc, 3 beta HSD and P450c17 was observed
      in large-sized preantral follicles, consisting of more than five layers of
      granulosa cells, preovulatory follicles, corpora lutea, and some degenerating
      corpora lutea and atretic follicles in all endometrial phases. Several follicles
      and/or corpora lutea positive for these enzymes were observed in the same ovary.
      Expression of P450arom was generally observed in only one follicle (antral or
      preovulatory follicle) or corpus luteum per case in mid proliferative to
      premenstrual phase, and was not observed in menstrual to early proliferative
      phase. These findings indicated that (1) expression of steroidogenic enzymes was
      associated with the continual human ovarian process including follicular
      development and atresia, and (2) especially, P450arom expression may occur only
      in a selected antral follicle and may have an important role in dominant
      follicular development.

PMID- 8143897
TI  - Competitive inhibition of thyroid hormone uptake into cultured rat brain
      astrocytes by bilirubin and bilirubin conjugates.
AB  - Thyroid hormone (TH) metabolism is altered in cases of unconjugated
      hyperbilirubinemia. These effects might involve inhibition of TH uptake by their
      target cells. Astrocytes, which are in close contact with the membranes of brain
      capillaries, might be the first brain cells to come into contact with bilirubin.
      Cultured rat brain astrocytes were used as a model to study the effects of
      bilirubin and bilirubin analogues on TH uptake. The initial uptake of [125I]T3
      and [125I]T4 was inhibited by unconjugated bilirubin, biliverdin,
      ditaurobilirubin and bilirubin glucuronides. The inhibition of T3 uptake by the
      bilirubin analogues was competitive. The Ki values were: unconjugated bilirubin
      (31 microM), biliverdin (48 microM), ditaurobilirubin (2.5 microM) and bilirubin
      glucuronides (1.2 microM). This last value is similar to the Km of T3 transport
      (0.4 microM), indicating that bilirubin glucuronides have a high affinity for the
      TH transport system. By contrast, the uptakes of [3H]tryptophan and ]3H]glutamine
      were not inhibited. These results suggest that the astrocyte plasma membrane
      bears specific bilirubin-interaction sites that are closely related to the TH
      transport system. However, uptake of [14C]bilirubin by cultured astrocytes was a
      non-saturable process. Binding of bilirubin to the astrocyte plasma membrane may
      inhibit the TH uptake and impair their metabolism and their action on the
      intracellular targets.

PMID- 8143898
TI  - Competitive PCR for quantitation of gonadotropin-releasing hormone mRNA level in
      a single micropunch of the rat preoptic area.
AB  - A competitive polymerase chain reaction (PCR) for quantitating gonadotropin
      releasing hormone (GnRH) mRNA level in a single micropunch of the rat preoptic
      area (POA) is described. The POA (600 microns in depth) was micropunched from
      frozen rat brain slices and used for mRNA isolation using Dynabeads-oligo(dT)
      magnetic separation technique. The target RNA combined with a synthetic, deletion
      mutant GnRH cRNA as an internal standard, is co-reverse transcribed, and their
      cDNAs are subsequently co-amplified by Taq DNA polymerase in the same tube in
      which the same GnRH primers are used. This PCR protocol is sensitive enough to
      detect GnRH mRNA level in a single POA micropunch derived from an individual rat.
      There is a linear increase of the amount of GnRH PCR products as a function of
      input RNA and of the number of PCR cycles. Addition of mutant GnRH cRNA as an
      internal standard allows us to quantitate GnRH mRNA level in biological samples
      and to compensate variations of PCR reaction between samples. Following preoptic
      treatment with 5'-ADMP, which depletes selectively norepinephrine (NE), GnRH mRNA
      level was significantly reduced. This simple, yet highly sensitive PCR method
      appears to be a valuable tool for the study of the cellular and molecular
      regulation of GnRH gene expression in a variety of experimental models.

PMID- 8143899
TI  - Expression of the genes encoding bombesin-related peptides and their receptors in
      anterior pituitary tissue.
AB  - The bombesin-related peptides gastrin-releasing peptide (GRP) and neuromedin B
      (NMB) have been demonstrated in the anterior pituitary (AP) on an immunological
      basis. We studied the presence of mRNAs for these peptides and for their
      receptors by RNAse protection assay using fresh adult male rat AP, AP cell
      reaggregates cultured in the presence of estradiol and the rat AP derived GH3
      cell line. In total RNA from fresh AP we detected high amounts of NMB mRNA and
      much smaller amounts of GRP mRNA, while finding a weak signal for GRP-receptor
      (GRP-R) and NMB-receptor (NMB-R) mRNAs. In total RNA from the reaggregate cell
      cultures we detected high levels of NMB mRNA as well as a strong signal for GRP-R
      mRNA. Finally, in GH3 cells, high levels of NMB mRNA and GRP-R mRNA were found,
      while GRP mRNA and NMB-R mRNA remained undetectable even in high amounts (200
      micrograms) of total RNA. We conclude that mRNAs encoding both bombesin-related
      peptides and each of the mRNAs encoding their receptors are expressed in rat AP
      tissue. NMB mRNA is more prominent than GRP mRNA in all AP-like tissues examined
      (fresh AP, estradiol-treated reaggregate AP cell cultures and GH3 cells). NMB-R
      mRNA and GRP-R mRNA are both present in low levels in fresh AP whereas the GRP-R
      mRNA is predominant in GH3 cells and estradiol treated AP reaggregate cell
      cultures. Compared to fresh AP tissue, NMB mRNA and GRP-R mRNA expression is
      enhanced in estradiol-treated reaggregate cell cultures.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8143900
TI  - Characterization of a corticotropin releasing hormone responsive region in the
      murine proopiomelanocortin gene.
AB  - The most potent, physiologic activator of proopiomelanocortin (POMC) gene
      transcription is corticotropin releasing hormone (CRH) and increased
      intracellular cAMP is critical for this effect. The 5'-flanking region of the
      murine POMC gene has several potential binding sites for regulatory proteins. To
      characterize the region between nucleotides -141 and -106, which includes a TRE
      like site and an adjacent AP-2 consensus sequence, and to study its role in
      signal-transcription coupling, gel mobility shift assays and transient expression
      of CAT chimeras were performed. In transient transfections of AtT-20 cells with
      pCATp-141/-106, CRH treatment led to significant increases in CAT expression
      compared with CRH treatment of cells transfected with the enhancerless vector.
      However, no response to direct activation of cAMP dependent protein kinase or
      protein kinase C was detected. Despite the high homology of the sequence -137/
      131 to the consensus AP-1 binding site (TRE), the nuclear factor(s) in AtT-20
      cells binding to this region appears to be different than authentic AP-1 since
      neither a competitor oligonucleotide having the authentic TRE sequence nor
      antibodies against Jun or Fos affected the gel shift pattern of a probe having
      the -137/-131 sequence. We conclude that the -141 to -106 region of the murine
      POMC gene contains a functional CRH responsive element and that second messenger
      systems that transduce the CRH signal to this element do not exert their actions
      solely through activation of PKA or PKC.

PMID- 8143901
TI  - A receptor binding site identified in the region 81-95 of the beta-subunit of
      human luteinizing hormone (LH) and chorionic gonadotropin (hCG).
AB  - Two series of overlapping peptides comprising the entire sequences of the beta
      subunits of human lutropin (LH) and choriogonadotropin (hCG) were prepared by a
      comprehensive synthetic strategy in order to identify all linear regions of the
      subunit that may participate in binding of the hormone to its receptor. Each
      series of peptides (15 residues in length) spanned the entire amino acid
      sequences of the two beta-subunits. The peptides were tested for their ability to
      inhibit the binding of 125I-labeled hCG or LH to rat ovarian membranes and for
      their ability to inhibit hCG-stimulated progesterone production in a Leydig cell
      bioassay. The most potent inhibitor of LH/hCG binding was a peptide containing
      the sequence beta 81-95, a receptor binding site of the LH/hCG beta subunit not
      previously described. The concentration at which LH/hCG binding was inhibited at
      50% (IC50) was 20 microM and 30 microM for hCGbeta 81-95 and LH beta 81-95,
      respectively. These peptides also inhibited the stimulation of progesterone
      production by hCG in Leydig cell bioassays. In order to determine important
      residues that inhibit binding within this region, a third set of peptides was
      synthesized in which each residue of hCG beta 81-95 was sequentially replaced
      with the residue L-alanine. Five residues (Leu-86, Cys-88, Cys-90, Arg-94, and
      Arg-95) were critical for maximal inhibition of hCG binding by CG beta 81-95. In
      addition to site beta 81-95, other sites that inhibited hCG/LH binding but with
      significantly lower potencies included hCG beta 1-15, LH beta 41-55, and LH beta
      91-105.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143902
TI  - The effects of follistatin, activin and inhibin on steroidogenesis by bovine
      thecal cells.
AB  - The paracrine actions of bovine follistatin (FS), human recombinant activin A and
      bovine inhibin on progesterone (P), androstenedione (A4) and inhibin production,
      were investigated using LH-stimulated immature bovine thecal cells. The presence
      of FS (3-100 ng/ml) alone caused a dose-dependent stimulation of P production by
      thecal cells induced by bovine LH (10 ng/ml). The stimulatory effect of FS on P
      production at 10 or 30 ng/ml was reversed to control levels with the addition of
      activin (10 or 30 ng/ml). Treatment with FS did not significantly effect on A4
      production. Activin alone had no consistent effect on A4 production (measured
      using two different antibodies), but had a dose-dependent inhibitory effect on P
      production. Treatments of cells with inhibin had no significant effect on the LH
      induced production of either P or A4. Testosterone production in FS; activin- or
      inhibin-treated cells was not different from controls. Northern analysis showed
      that inhibin beta subunit was not detected in thecal mRNA, whereas there were
      very faint bands of inhibin alpha subunit and FS which were attributed to
      contamination of granulosa cells (GC). We conclude that FS in vitro has a
      stimulatory effect on P production by bovine thecal cells, and that activin has
      the ability to reverse the stimulatory effect of P production. Unlike the rat and
      human thecal cells, activin and inhibin had no significant effect on LH-induced
      androgen synthesis by bovine thecal cells. We propose that FS secreted by the GC
      acts as a paracrine modulator upon thecal cells to directly stimulate the
      production of P independently of activin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143903
TI  - Expression of the IGF system in primary and immortalized porcine ovarian
      granulosa cells.
AB  - We have established a novel granulosa cell line derived from porcine ovarian
      follicles (4-6 mm in diameter). This cell line, MDG2.1, was obtained by
      transfection of freshly cultured cells with the plasmid pSV3neo. Doubling time
      for MDG2.1 cells is 24-36 h. Northern analysis for RNAs of the insulin-like
      growth factor (IGF) regulatory system indicates that RNAs for IGF-I, IGF-I
      receptor, and IGF binding proteins (IGFBP) 2-6, but not IGFBP-1, are expressed in
      MDG2.1 cells. The secretion of IGFBPs from MDG2.1 cells shows > 10-fold levels of
      the 24 kDa form, reduced secretion of other IGFBPs, with no change in the total
      amount of IGFBP secreted, as compared to primary cells cultured under identical
      conditions. Use of endoglycosidase F indicated that several IGFBPs are
      posttranslationally modified. This cell line is a useful model and plasmid
      transfection target system to investigate IGFBP action in ovarian granulosa
      cells.

PMID- 8143904
TI  - Involvement of protein kinase C and protein tyrosine kinase pathways in tumor
      necrosis factor-alpha-induced clustering of ovarian theca-interstitial cells.
AB  - Tumor necrosis factor-alpha (TNF) induces clustering of theca-interstitial cells
      (TIC) isolated from immature, hypophysectomized rats, while inhibiting
      luteinizing hormone (LH)-stimulated androstenedione in vitro. Stimulators of PKC,
      1-oleoyl-2-acetyl-sn-glycerol (OAG, 50 and 100 microM) and phorbol-12-myristate
      13-acetate (PMA, 50 nM), caused TIC clustering by 6 days in vitro. Clustering
      induced by these compounds resembled that induced by TNF. The protein kinase
      inhibitor, staurosporine at 1 and 10 nM, impaired TNF-induced TIC clustering for
      6 days, as did the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2
      methylpiperizine dihydrochloride (H-7); conversely, the protein kinase inhibitor,
      chelerythrine chloride (0.1, 1.0 or 10 microM), did not attenuate TNF-directed
      clustering. The protein kinase inhibitors did not reverse the suppression of LH
      stimulated androstenedione by TNF. Inhibitors of the EGF receptor PTK, A23 (10,
      50, or 100 microM) and A46 (0.1, 1.0, 10, or 50 microM), impaired TNF-induced TIC
      clustering, while TNF suppression of LH-directed androstenedione was unaffected.
      EGF-induced TIC clustering was also impaired by A46, while A23 was less
      effective. Both A23 and A46 blocked EGF attenuation of LH-directed
      androstenedione after 4 days. When challenged with TNF (1 ng/ml) or PMA (50 nM),
      PKC activity increased in TIC. A23 (50 microM) and A46 (10 microM) each alone
      blocked the TNF-associated increase in PKC activity; however, PKC activity
      attributable to PMA was unaffected by A46. Together, these results suggest that
      TNF-induced TIC clustering involves activation of PTK which directs subsequent
      increases in PKC activity; however, mechanisms by which TNF inhibits LH
      stimulated steroidogenesis remains elusive.

PMID- 8143905
TI  - Hormonal storage patterns and morphological heterogeneity of porcine gonadotrope
      cells during postnatal development.
AB  - Previous reports indicate that gonadotrope cells of the porcine pituitary gland
      can be separated into three subpopulations of low- (1.049 g/cm3), middle- (1.062
      g/cm3) and high- (1.087 g/cm3) density in a continuous Percoll density gradient.
      The aim of this work was to study the hormonal storage patterns and morphological
      features of these subpopulations at three representative ages of the postnatal
      development: neonatals (30-day-old animals), prepubertals (5-6-month-old animals)
      and matures (16-18-month-old animals). The low-density subpopulation, present at
      the three ages studied, was mainly composed of bihormonal LH/FSH cells in
      neonatal and monohormonal LH cells in prepubertal and mature animals. On the
      other hand, middle- (only present in prepubertal and mature animals) and high
      density subpopulations (only present in neonatal and prepubertal animals) were
      mainly composed of bihormonal LH/FSH gonadotropes. In ultrastructural terms,
      these subpopulations exhibit a correlation between density and morphology
      irrespective of the animal's age. The low-density subpopulation was composed of
      poorly granulated cells with highly developed biosynthetic machinery (rough
      endoplasmic reticulum and Golgi complex), while high-density cells were of
      opposite morphology, with a highly granulated cytoplasm and poorly developed
      rough endoplasmic reticulum and Golgi complex. The middle-density subpopulation
      was composed of poorly granulated cells with scarcely developed biosynthetic
      machinery. In conclusion, these results indicate that porcine gonadotrope cells
      during postnatal development are composed of three subpopulations of different
      hormonal storage patterns and morphology. The presence of these subpopulations at
      the different stages of postnatal development strongly suggests that their
      proportions may play a major role in the endocrine control process.

PMID- 8143906
TI  - Calbindin-D9k gene expression during the perinatal period in the rat: correlation
      to estrogen receptor expression in uterus.
AB  - Calbindin-D9k (CaBP-9k) is a cytosolic calcium binding protein mainly expressed
      in duodenum, placenta and uterus. The gene encoding the rat CaBP-9k is subject to
      tissue specific induction by 1,25 dihydroxyvitamin D3 (intestine) and estradiol
      (E2) (uterus). Control of placental expression remains unknown. The expression of
      CaBP-9k mRNA during the perinatal period was studied (pregnancy day 21 (P21)
      lactation day 4 (L4)). In uterus, maximal expression levels were found at P21 and
      maintained until L1. With the transition to L2, the CaBP-9k mRNA concentration
      dropped drastically below the detection limit as quantitated by Northern blot
      analysis. Measurements of E2 and progesterone (P) levels showed a gradual
      decrease at late pregnancy (P21; birth). Post partum E2 levels continued to
      decline and P concentrations increased slightly. Uterine estrogen receptor (ER)
      mRNA levels determined by cDNA/PCR analysis revealed close correlation between
      expression of ER and CaBP-9k mRNAs. ER mRNA levels were maximal at P22 and
      declined at parturition and with onset of lactation. At L2 and L3 ER mRNA levels
      were minimal and had decreased 5-fold compared to late pregnancy. CaBP-9k protein
      concentrations fluctuated only slightly dependent on the stage of the estrous
      cycle: estrus > proestrus > diestrus. During the perinatal period CaBP-9k
      concentration was overall lower than in non-pregnant uterus and revealed only a
      moderate increase at birth and decrease in early lactation. Similar to the
      uterine levels, placental CaBP-9k mRNA was highest at P21 and remained high until
      birth. Fetal duodenal CaBP-9k rose sharply just prior to birth and plateaued in
      the early postpartal period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143907
TI  - Mode of action of prostaglandin F2 alpha in human luteinized granulosa cells:
      role of protein kinase C.
AB  - It is well documented that prostaglandin F2 alpha (PGF2 alpha) inhibits
      progesterone production in luteal cells, but its mode of action is uncertain. It
      has recently been suggested that PGF2 alpha acts by activating the calcium and
      phospholipid-dependent protein kinase, protein kinase C (PKC). This hypothesis
      has been tested by comparing the site and mode of action of PGF2 alpha, a PGF2
      alpha analogue (cloprostenol) and the PKC activator phorbol myristate acetate (4
      beta PMA) in human granulosa-lutein cells. PGF2 alpha and cloprostenol exerted
      similar concentration-dependent inhibitory actions on gonadotrophin-stimulated
      cyclic AMP (cAMP) accumulation and progesterone production by human granulosa
      lutein cells. The similarity in the actions of PGF2 alpha and cloprostenol in
      human granulosa-lutein cells suggests that they can be used interchangeably to
      study the role of PGF2 alpha in the regulation of steroidogenesis in the human
      ovary. Gonadotrophin-stimulated cAMP accumulation and progesterone production was
      also concentration-dependently inhibited by 4 beta PMA. In addition, cloprostenol
      and 4 beta PMA also inhibited dibutyryl cAMP-stimulated progesterone production,
      suggesting that these compounds inhibit LH action at sites before and after the
      generation of cAMP. The pre-cAMP site of action can be localised to the
      stimulatory G-protein (Gs) as both compounds inhibited cholera toxin-stimulated
      cAMP accumulation without affecting forskolin-stimulated cAMP accumulation. The
      post cAMP site of action can be localised to actions on cholesterol side chain
      cleavage enzyme, as both cloprostenol and 4 beta PMA inhibited 22R
      hydroxycholesterol-supported progesterone production without affecting
      pregnenolone-supported progesterone production. The finding that cloprostenol and
      4 beta PMA interact with the steroidogenic cascade in a similar manner is
      indicative of a shared common mediator of their actions in human granulosa-lutein
      cells, i.e. PKC. The inhibitory actions of PGF2 alpha and 4 beta PMA on hLH
      stimulated progesterone production were abolished in the presence of the PKC
      inhibitor, staurosporine. In addition, in PKC-depleted cells (achieved by
      exposure to 4 beta PMA for 20 h) the inhibitory actions of PGF2 alpha and 4 beta
      PMA were abolished. These results support the hypothesis that the inhibitory
      actions of PGF2 alpha are mediated by PKC in human granulosa-lutein cells.

PMID- 8143908
TI  - Hepatic tyrosine-phosphorylated proteins identified and localized following in
      vivo inhibition of protein tyrosine phosphatases: effects of H2O2 and vanadate
      administration into rat livers.
AB  - Injection of a combination of H2O2 and vanadate (H/V) into the portal vein of rat
      livers resulted in inhibition of protein tyrosine phosphatase activity and led to
      a dramatic enhanced in vivo protein tyrosine phosphorylation. Some of the
      phosphorylated proteins were identified as the beta-subunit of the insulin
      receptor, the insulin receptor substrate 1 (pp185), PLC-gamma (pp145), and a 100
      kDa PLC-gamma-associated protein. Immunofluorescense and immune electron
      microscopy of frozen liver sections with anti-P-Tyr antibodies revealed that most
      of the tyrosine-phosphorylated proteins are localized in close proximity to the
      plasma membrane in intercellular adherence junctions and tight junction regions.
      This close in vivo association between membranal protein tyrosine kinases, their
      target proteins, and cytoskeletal elements could enable formation of 'signaling
      complexes' which may play a role in transmembrane signal transduction. By
      affinity chromatography over immobilized anti-P-Tyr antibodies, a large number of
      these tyrosine-phosphorylated proteins were partially purified.

PMID- 8143909
TI  - Characteristics of a membrane-associated antilactogen binding site for tamoxifen.
AB  - The antilactogen binding site (ALBS) is a membrane associated protein to which
      tamoxifen (TAM) and related non-steroidal antiestrogens, but not estrogen, bind.
      It is through this site that TAM inhibits lactogen binding to the prolactin (Prl)
      receptor and subsequent Prl induced growth and differentiation in target tissues.
      Binding of lactogens to the Prl receptor is inhibited by TAM or 4-hydroxy-TAM at
      4 degrees C as well as room temperature, thus suggesting that the ALBS is not an
      enzyme. TAM acts by inhibiting the binding of lactogens to the receptor rather
      than promoting dissociation of the hormone-receptor complex. Lactogens bind to
      mammary gland membranes with an Kd of 4.3-8.2 x 10(-10) M. In the presence of 10(
      7) M TAM the affinity decreased to a Kd of 0.8-1.6 x 10(-9) M. Binding of 3H-TAM
      to mammary gland membranes was effectively inhibited by an anti-Prl receptor
      antibody, thus suggesting a close relationship between the Prl receptor and the
      ALBS. Separate affinity purification of the ALBS and the Prl receptor resulted in
      peak fractions demonstrating specific binding activity for both TAM and
      lactogenic hormones. Re-isolation of the affinity purified Prl receptor on a TAM
      Sepharose affinity resin again resulted in co-elution of both binding activities.
      The isolates from both affinity resins contained primarily a single band with an
      apparent molecular mass of 90 kDa. This band was precipitated with the anti-Prl
      receptor antibody and specifically bound the affinity label ring-3H-TAM
      aziridine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143910
TI  - Inhibition by genistein of prolactin-induced Nb2 lymphoma cell mitogenesis.
AB  - Tyrosine kinase activation in mediating the mitogenic action of prolactin (PRL)
      has been evaluated. Use was made of genistein, a tyrosine kinase antagonist, and
      cultured rat Nb2 lymphoma cells, i.e. the lactogen-dependent Nb2-11 line and a
      lactogen-independent subline, Nb2-SFJCD1. Genistein was found to be a potent
      growth-inhibitor for both lines, inhibiting 3H-thymidine incorporation in Nb2-11
      and Nb2-SFJCD1 cells with IC50s of 4.2 and 6.7 micrograms/ml, respectively.
      Genistein also inhibited expression and translation of the heat shock protein 70
      gene and pp40 protein substrate phosphorylation which, in Nb2-11 cells, followed
      PRL addition within minutes. Genistein inhibition of DNA synthesis in G1-arrested
      Nb2-11 cells was most pronounced if the agent was added within 1 h of PRL
      treatment. The results indicate that, while both Nb2 cell lines have a general
      growth requirement for tyrosyl phosphorylation, the early, PRL-induced tyrosine
      kinase activation is a component of the PRL mitogenic signal transduction
      pathway.

PMID- 8143911
TI  - Spi-1: an hepatic serine protease inhibitor regulated by GH and other hormones.
AB  - A sensitive RNAse protection method was used to show that serine protease
      inhibitor-1 (Spi-1) is expressed in rat liver and heart, but not in kidney or
      brain. Bovine somatotropin (bGH) and placental lactogen (bPL) induced rat
      hepatocyte cultures to express both Spi-1 and IGF-1 mRNA, with bPL approximately
      100-fold more potent than bGH. Bovine prolactin (bPrL) did not induce hepatocyte
      Spi-1 mRNA, demonstrating lack of involvement of lactogenic receptors. Albumin
      mRNA levels were stable during hepatocyte culturing and were unaffected by growth
      hormone (GH) treatment, showing that neither culture conditions nor GH treatment
      affected cellular differentiation. Eliminating serum-free medium hormone
      supplements one at a time, estradiol, testosterone and T3 were shown to be
      unnecessary for GH induction of Spi-1, while dexamethasone removal decreased Spi
      1 mRNA levels to 10% of GH-stimulated controls. bGH induction of Spi-1 mRNA in
      the presence of only dexamethasone and glucagon was 75% higher (p < 0.01) than
      levels seen with insulin also present.

PMID- 8143912
TI  - Physiological regulation of melatonin receptors in rat suprachiasmatic nuclei:
      diurnal rhythmicity and effects of stress.
AB  - A marked diurnal variation in high-affinity binding of 2-[125I]iodomelatonin
      ([125I]MEL) in rat brain sections containing the suprachiasmatic nuclei (SCN) was
      observed. Binding was highest late in the light phase and lowest during darkness,
      in inverse correlation to the serum melatonin rhythm. Interestingly, only high
      affinity sites were present during most of the light phase while both high- and
      low-affinity sites were detected just before and during darkness. Guanosine
      triphosphate (GTP) in combination with sodium converted all high affinity sites
      to a low affinity state suggesting that the two sites observed during darkness
      represent the two states of the melatonin receptor. Acute swim-stress caused a
      significant elevation of serum melatonin, together with a decrease in the density
      of [125I]MEL binding in the SCN. The inverse relationship between circulating
      melatonin levels and binding, under two different physiological conditions,
      indicates that this hormone is involved in regulating its own receptors in the
      SCN.

PMID- 8143913
TI  - Tissue-specific expression of heat shock proteins 70 and 90: potential
      implication for differential sensitivity of tissues to glucocorticoids.
AB  - Heat shock proteins (hsps) and glucocorticoids are key elements of the organism's
      adaptive response to adverse physiological conditions. Glucocorticoids are
      pleiotropic hormones acting through receptor-mediated processes and eliciting
      tissue-specific biologic effects. The inactive form of the glucocorticoid
      receptor (GR) in the cytoplasm appears to be bound to hsps of the 90K family
      (hsp90 alpha and hsp90 beta). This interaction facilitates binding of
      glucocorticoid to its receptor, and depends on the relative amounts of the
      interacting components, GR and hsp90. To gain insight into the mechanisms of
      glucocorticoid regulation in a physiological context, the level of the hsp70/90
      system in a panel of tissues, including testis, spleen, liver, thymus, pituitary,
      hypothalamus, hippocampus, brain cortex, pineal and adrenal, was examined by
      Western blotting. The hsp90 component showed greater variation (up to about forty
      fold) relative to the less variable (up to about three-fold) hsp70 component of
      the system. The relative distribution of the hsp90 alpha and beta forms in the
      various tissues was also examined by a combination of Western and Northern
      blotting techniques. It was found that the alpha form predominated in the brain
      and the testis and the beta form predominated in the other peripheral organs.
      There was no relation between tissue hsp90 content and differential expression of
      either form. These findings suggest that tissue hsp90 content, an important
      physiological parameter of cellular homeostasis, may confer tissue specificity
      and sensitivity to glucocorticoids.

PMID- 8143914
TI  - Effects of transforming growth factor beta and epidermal growth factor on steroid
      5 alpha-reductase activity in genital skin fibroblasts.
AB  - Regulation of steroid 5 alpha-reductase (5 alpha R) activity and
      dihydrotestosterone (DHT) formation is central to prostate and sexual skin (hair)
      growth and cell function. Transforming growth factor-beta 1 (TGF-beta 1) is a
      ubiquitous peptide present in skin and scrotal tissue and its receptor is
      universally expressed. We have explored the role of TGF-beta 1 and -beta 2 on
      androgen formation in skin. Rat or human sexual skin fibroblasts were grown in
      primary cultures (passage 3-7). 5 alpha-Reductase activity was measured by the %
      conversion of tracer 3H-testosterone to dihydrotestosterone over a 4 h period.
      Incubation of scrotal fibroblasts (2 x 10(5) cells) in serum and growth factor
      free media with androgen, such as DHT for two days significantly stimulates 5
      alpha R in these cells (1.6-fold, p < 0.05 vs control). TGF-beta 1 alone at
      picomolar concentrations (2 x 10(-11) M to 2 x 10(-10) M) was a potent inducer of
      5 alpha R activity in both rat (1.8-fold and 2.8-fold, respectively, p < 0.001 vs
      control at both doses) and human cells (TGF-beta 1 2 x 10(-10) M 3.3-fold, p <
      0.001 vs control). Combined exposure of these fibroblasts to TGF-beta 1 (2 x 10(
      10) M) and androgen (10(-7) M) further potentiated 5 alpha R activity (rat cells
      6.5-fold, human cells 6.4-fold, p < 0.001 vs DHT or TGF-beta 1 alone).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8143915
TI  - The human vasopressin-oxytocin gene family: no evidence for additional
      neurophysin-related genes.
AB  - Over the last 20 years several observations at the peptide level have indicated
      the possible existence of additional members of the vasopressin (VP)-oxytocin
      (OT) gene family in mammals. In this study, the human genome was analyzed for the
      existence of genes structurally related to the VP and OT genes. Human genomic
      blots probed under low stringency conditions with exon B of the human OT gene,
      that codes for the conserved constant region of neurophysin, revealed the
      presence of two distinct bands in addition to the known VP and OT gene fragments.
      Five clones were obtained from a library of genomic EcoRI fragments ranging from
      4-8 kb, that comprised both low stringency signals, by low stringency
      hybridization with the OT exon B probe. One clone of 7 kb hybridized at high
      stringency conditions to bands of the same size as previously detected with OT
      exon B on a human genomic blot. However, no similarity was observed between the
      open reading frames of this clone and the neurophysin portion of the OT gene.
      Another clone of 4.8 kb was identical to a fragment of the gene for the human
      bone morphogenetic factor hBMP-6, a member of the TGF-beta family. The hBMP-6
      gene was not detected by low stringency hybridization of the human genomic blot
      with the OT exon B probe. No significant similarity was found between the amino
      acid sequences of human OT neurophysin and hBMP-6. Therefore, no evidence can be
      provided that the human genome contains additional neurophysin-related
      genes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143916
TI  - Differential effects of prepubertal rat Sertoli cell secreted proteins on somatic
      testicular and nontesticular cells.
AB  - There is little information on the mitogenic and immunoregulatory activities of
      proteins, secreted by prepubertal Sertoli cells during the stage of meiosis
      initiation and before creation of the blood-testis barrier. We have previously
      demonstrated dose-dependent and age-related stimulation of BALB/c 3T3 fibroblasts
      and quiescent rat prespermatogonia (Kancheva et al., 1990) as well as inhibition
      of natural killer cell activity of mice, guinea pigs and human lymphocytes
      (Nikolova et al., 1992) by Sertoli cell-conditioned medium derived from 12-day
      old rats. In the current study, using splenic lymphocytes stimulated by PHA, LPS
      and Con A, we have shown a dose-dependent inhibition of T and B lymphocyte
      proliferation by prepubertal Sertoli cell-secreted proteins (pSCSP). These
      results suggest that by the time the blood-testis barrier had been formed,
      Sertoli cell in rat testis had already synthesized immunoregulatory proteins. In
      addition we have found that pSCSP stimulate the proliferation of TM3 Leydig but
      not TM4 Sertoli cells. The differential effect of pSCSP is an expression of the
      different balance between growth factors secreted by Sertoli cells, which in turn
      is dependent on the requirements of the cell types at each stage of testicular
      development.

PMID- 8143917
TI  - Evidence that both receptor- and heparan sulfate proteoglycan-bound basic
      fibroblast growth factor are internalized by cultured immature Leydig cells.
AB  - The present studies examined how 125I-labeled basic fibroblast growth factor
      (bFGF) bound to high affinity receptors and with lower affinity to heparan
      sulfate proteoglycans (HSPG) of cultured immature rat Leydig cells was processed.
      Following incubation for 2 h at 4 degrees C with 125I-bFGF, cells were washed to
      remove unbound radioactivity. Fresh medium was added, and cells were incubated at
      4 degrees and/or 37 degrees C. At time zero and at specific intervals over the
      next 6 h, the incubation medium was saved and cells washed to quantitate 125I
      bFGF released into the medium, associated with HSPG of the cell surface or
      extracellular matrix (radioactivity released by washing cells with 2 M NaCl, pH
      7.4), associated with cell surface receptors (radioactivity released by washing
      cells with 2 M NaCl, pH 4.0) or internalized (radioactivity resistant to high
      salt and acid washes, and solubilized with 0.5 M NaOH). Radioactivity released
      into the initial medium and the pooled washes was further divided into a
      trichloroacetic acid (TCA)-precipitated form (radioactivity precipitated by 10%
      TCA) and a TCA-soluble form (radioactivity remaining in the TCA supernatant).
      125I-bFGF associated with both HSPG and surface receptors declined progressively
      during the first 4 h of incubation before stabilizing when cells were transferred
      to 37 degrees C. These declines were associated with a corresponding increase in
      intracellular 125I-bFGF. These changes were blocked by maintaining cells at 4
      degrees C. The majority of internalized 125I-bFGF appeared to originate from the
      HSPG-bound fraction as there was a greater decline in HSPG-associated
      radioactivity and most of the increase in internalized radioactivity could be
      blocked by the inclusion of 10 micrograms/ml heparin (which mainly blocks 125I
      bFGF binding to HSPG but not to high affinity receptors) during the initial
      incubation with 125I-bFGF for 2 h at 4 degrees C. Furthermore, HSPG-mediated
      internalization appeared to have two components: the major fraction was blocked
      by the inclusion of 10 micrograms/ml heparin, while a heparin-resistant fraction,
      appeared to be closely linked both quantitatively and temporarily to receptor
      mediated internalization. A minor fraction of internalized 125I-bFGF was
      metabolized in lysosomes, as the inclusion of 50 microM chloroquine during the 6
      h incubation at 37 degrees C inhibited most of the increase in TCA-soluble
      radioactivity appearing in the incubation medium.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8143918
TI  - Reconstitution of protein kinase C alpha function by the protein kinase C beta-I
      carboxy terminus.
AB  - The Ca(2+)- and phospholipid-dependent Ser/Thr kinase protein kinase C (PKC)
      plays important roles in the transduction of cellular signals. Various PKC
      isoforms exist in mammalian cells which share conserved and variable regions as
      defined by cDNA sequence comparisons. To test whether carboxyl (C) terminal
      sequences of distinct isoforms can complement each other to yield functional
      chimeric molecules, we have constructed a PKC chimera in which amino acids 595
      672 at the C-terminus of bovine PKC alpha (a) were replaced with the
      corresponding C-terminal amino acids (598-671) of rat PKC beta-I (b) to yield the
      chimera alpha/beta-I (ab). The chimera was then characterized biochemically and
      functionally, and compared with the parental isoforms. Since structure/function
      analysis of PKC in mammalian experimental systems is complicated by multiple PKC
      isoforms and by cellular complexity, we stably introduced the PKC constructs into
      the yeast Saccharomyces cerevisiae, a simple, lower eukaryote with a short
      doubling time and well established molecular genetics. In yeast, the faithfully
      expressed PKCab chimera and normal PKC isoforms bound radiolabelled phorbol ester
      and were recognized on immunoblots by PKC-specific antibodies. The chimera
      phosphorylated substrate peptides in a PMA- and Ca(2+)-dependent manner, and,
      upon activation, increased the cell doubling time and the rate of Ca2+ uptake
      into cells. In addition, PKCab displayed characteristics distinct from normal
      PKCb, but virtually indistinguishable from normal PKCa. Our findings indicate the
      reconstitution of PKCa function by the PKCb carboxyl terminus.

PMID- 8143919
TI  - Sheep thyroxine-binding globulin: cDNA sequence and expression.
AB  - A full-length thyroxine-binding globulin clone was isolated from a sheep liver
      cDNA library. The nucleotide sequence consisted of 1379 nucleotides and contained
      the coding region of 1236 nucleotides. The deduced sequence of the mature protein
      was 396 amino acids long. The similarity of the sheep thyroxine-binding globulin
      amino acid sequence with those of human and rat were 80% and 76%, respectively.
      Expression of the thyroxine-binding globulin gene was investigated by Northern
      analysis. The gene was not expressed in choroid plexus nor at other extrahepatic
      sites. The expression of the thyroxine-binding globulin gene was also studied
      during sheep foetal development. Thyroxine-binding globulin mRNA was already
      detected in livers of 1 cm long foetuses and levels similar to those found in
      liver from adult sheep were reached half way through pregnancy.

PMID- 8143920
TI  - The biology and medicine of calcium signalling.
AB  - Calcium is a second messenger responsible for regulating a wide range of cellular
      processes. It is normally presented as brief spikes even in non-excitable cells.
      The necessity of limiting the period of calcium stimulation to brief bursts may
      depend upon the fact that prolonged elevation of calcium can be toxic. It can act
      on endonucleases in the nucleus to trigger programmed cell death. It will be
      argued that non-lethal effects of elevated calcium can lead to a variety of
      pathological conditions including hypertension, atherosclerosis, transformation,
      malignant hyperthermia and possible neural disorders such as spreading depression
      and manic-depressive illness.

PMID- 8143921
TI  - Cyclic ADP-ribose, the ADP-ribosyl cyclase pathway and calcium signalling.
AB  - Cyclic adenosine diphosphate-ribose, an endogenous metabolite of nicotinamide
      adenine dinucleotide was first characterized as a potent Ca2+ mobilizing agent in
      sea urchin eggs. Mounting evidence points to it being an endogenous activator of
      Ca(2+)-induced Ca2+ release by non-skeletal muscle ryanodine receptors in several
      invertebrate and mammalian cell types. Cyclic adenosine diphosphate-ribose is
      synthesized by adenosine diphosphate-ribosyl cyclases, which have been found to
      be widespread enzymes. Recent data suggests that cyclic adenosine diphosphate
      ribose may function as a second messenger in sea urchin eggs at fertilization and
      in stimulus secretion coupling in pancreatic beta-cells. A second messenger role
      for cyclic adenosine diphosphate-ribose requires that its intracellular levels be
      under the control of extracellular stimuli. Another second messenger, cGMP,
      stimulates the synthesis of cyclic adenosine diphosphate-ribose from nicotinamide
      adenine dinucleotide by activating the adenosine diphosphate-ribosyl cyclase
      pathway in sera urchin eggs and egg homogenates, suggesting that cyclic adenosine
      diphosphate-ribose may be an intracellular messenger for cell surface receptors
      or nitric oxide, which activate cGMP-producing guanylate cyclases. Cyclic
      adenosine diphosphate-ribose may have a similar role to inositol trisphosphate in
      controlling intracellular calcium signalling with these two calcium-mobilizing
      second messengers activating ryanodine receptors and inositol trisphosphate
      receptors respectively.

PMID- 8143922
TI  - The inositol 1,4,5-trisphosphate receptor: kinetic properties and regulation.
AB  - Inositol 1,4,5-triphosphate (InsP3) is a second messenger responsible for the
      mobilization of intracellular Ca2+ after receptor-mediated hydrolysis of
      phosphatidylinositol 4,5-bisphosphate. InsP3 binds to a specific receptor located
      on the membrane of an intracellular compartment and opens a Ca2+ channel causing
      the cytosolic Ca2+ concentration to increase. Measurement of radiolabelled InsP3
      binding and InsP3-induced Ca2+ release in parallel experiments indicated that the
      liver InsP3 receptor exists in two main states: an active state (A) and an
      inactive one (I). The "I" form of the receptor is found in the presence of high
      Ca2+ concentrations (above 1 microM). The binding properties of the "A" and the
      "I" states of the receptor have been characterized by analysing a membrane
      fraction enriched in InsP3 receptors. The inactive "I" state displays a high
      affinity (Kd = 2 nM) and slow rates of association and dissociation. The active
      state "A" of the receptor displays complex kinetic properties. The rate of
      association and the rate of dissociation of labelled InsP3 are rapid phenomena
      probably involving several components. The apparent Kd for the InsP3 binding is
      about 40 nM in a low Ca2+ medium. The affinity of the "A" state of the receptor
      is increased by Ca2+ (at concentrations lower than 0.5 microM) and by thiol
      reagents. The increase of the affinity of the receptor is due to a decrease of
      the dissociation rate constants. This lowers the threshold such that Ca2+ is
      released at lower concentrations of InsP3. These data indicate that the binding
      of InsP3 to its receptor is a complex phenomenon involving the transition among
      several states.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143923
TI  - Feedback control of inositol trisphosphate signalling bycalcium.
AB  - Inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release depends on the
      cytoplasmic concentration of Ca2+ in a biphasic manner: activated with the
      increase in Ca2+ up to approximately 300 nM and inhibited by its further
      increase. Kinetic studies of the Ca2+ release with rapid increase in Ca2+ or
      InsP3 using respective caged compounds indicated that the effects of Ca2+ appear
      immediately upon change in the Ca2+ concentration. Recovery from the Ca(2+)
      dependent inhibition seemed also rapid after reduction in the Ca2+ concentration.
      These results indicate that there is a Ca(2+)-mediated positive feedback control
      of InsP3-induced Ca2+ release below 300 nM Ca2+. This feedback control seems to
      explain, at least partly, the phenomenon that InsP3 is more effective in the Ca2+
      stores with greater Ca2+ loading. The Ca(2+)-mediated feedback control is also
      expected to give rise to temporally or spatially confined Ca2+ release as well as
      Ca2+ wave within the cells.

PMID- 8143924
TI  - Partial calcium release in response to submaximal inositol 1,4,5-trisphosphate
      receptor activation.
AB  - Even a prolonged application of a submaximal dose of Ins(1,4,5)P3 is unable to
      release the same amount of Ca2+ from the Ins(1,4,5)P3-sensitive store as a higher
      dose of Ins(1,4,5)P3. Low doses of Ins(1,4,5)P3 therefore only induce a partial
      release of the stored Ca2+. In this review, we will focus on the mechanisms that
      may contribute to this behaviour. Molecular heterogeneity of the Ins(1,4,5)P3
      receptor can contribute to such behaviour if all the gene products and
      alternatively spliced isoforms would have different functional properties and be
      located in different store units. We will show that the control of the
      Ins(1,4,5)P3 receptor by by luminal Ca2+ also contributes to the partial release
      behaviour; it can set the sensitivity of the Ins(1,4,5)P3 receptor and the
      decreasing luminal Ca2+ concentration may inhibit further release while some Ca2+
      is still left in the store. It is finally possible that the Ins(1,4,5)P3 receptor
      may adapt to a maintained stimulus.

PMID- 8143925
TI  - Quantal Ca2+ release from InsP3-sensitive intracellular Ca2+ stores.

PMID- 8143926
TI  - The control of intracellular signal molecules at the level of their hydrolysis:
      the example of inositol 1,4,5-trisphosphate 5-phosphatase.

PMID- 8143927
TI  - Mechanisms and function of intercellular calcium signaling.
AB  - Intercellular Ca2+ waves initiated by mechanical or chemical stimuli propagate
      between cells via gap junctions. The ability of a wide diversity of cells to
      display intercellular Ca2+ waves suggests that these Ca2+ waves may represent a
      general mechanism by which cells communicate. Although Ca2+ may permeate gap
      junctions, the intercellular movement of Ca2+ is not essential for the
      propagation of Ca2+ waves. The messenger that moves from one cell to the next
      through gap junctions appears to be IP3 and a regenerative mechanism for IP3 may
      be required to effect multicellular communication. Extracellularly mediated Ca2+
      signaling also exists and this could be employed to supplement or replace gap
      junctional communication. The function of intercellular Ca2+ waves may be the
      coordination of cooperative cellular responses to local stimuli.

PMID- 8143928
TI  - Expression of transforming growth factor-beta 2 and beta 3 mRNAs and proteins in
      the developing chicken embryo.
AB  - Specific cDNA probes and antibodies for chicken transforming growth factor (TGF)
      beta 2 and beta 3 were used to study expression of TGF-beta 2 and beta 3 mRNAs
      and proteins in the developing chicken embryo. Expression of the mRNAs for both
      TGF-beta isoforms was detected by day 1.5 of incubation (Hamburger and Hamilton
      stage 10) by RNA Northern blot analysis and increased with developmental age.
      Expression of TGF-beta 2 and beta 3 mRNAs was detected in every embryonic tissue
      examined, with the level of expression of both isoforms being high in heart,
      brain and muscle and low in kidney and liver. Coordinate unidirectional
      upregulation of expression of TGF-beta 2 and beta 3 mRNAs occurred in most
      embryonic tissues with development except the heart, where the steady-state level
      of expression of TGF-beta 2 mRNA decreased with age, while that of TGF-beta 3
      mRNA increased. In situ hybridization analysis detected TGF-beta 2 and beta 3
      mRNAs as early as the definitive primitive streak stage (stage 4). During
      neurulation (stage 10), TGF-beta 2 and beta 3 mRNAs were detected in cells of all
      three germ layers; TGF-beta 3 mRNA was detected in neurectoderm as well.
      Following neurulation, TGF-beta 3 mRNA was detected in the neural tube,
      notochord, ectoderm, endoderm, sclerotome and dermomyotome at stage 16;
      expression of TGF-beta 2 mRNA was not as prominent as TGF-beta 3 mRNA in these
      structures. By stage 29, both TGF-beta 2 and beta 3 mRNAs were localized in
      several tissues including heart, lung, gizzard and feathers. Immunohistochemical
      staining analysis detected immunoreactive TGF-beta 2 and beta 3 proteins in all
      three germ layers of stage 4 embryos. Staining for TGF-beta 2 and beta 3 proteins
      was detected in several cell types and tissues in the early developing embryo
      frequently in the same locations as TGF-beta 2 and beta 3 mRNAs, with staining
      for TGF-beta 2 being less intense than TGF-beta 3. However, in some cases,
      localization of TGF-beta 2 and beta 3 proteins was different from that of the
      mRNAs, indicating that a complex mechanism of transcription, translation and
      secretion exits during chicken embryogenesis. These and other results suggest
      that TGF-beta 2 and beta 3 may play important roles and act through both
      autocrine and paracrine mechanisms in the development of many tissues in the
      chicken.

PMID- 8143929
TI  - Synthesis, characterization and hormonal regulation of epididymal proteins during
      postnatal development of the mouse.
AB  - Maturation of mammalian spermatozoa depends on their interactions with epididymal
      proteins. The incorporation of 35S-methionine into these proteins was
      investigated by in vitro incubation of tissue minces from the mouse epididymis at
      different ages of postnatal development. The greatest amount of incorporation per
      wet weight of tissue was seen in 7 to 21-day-old mice. It decreased progressively
      during development while the rate of proteins released into the medium remained
      almost constant until the adult state. Separation of labeled proteins on sodium
      dodecyl sulphate polyacrylamide gels followed by fluorography showed that the
      great majority of secretory proteins synthesized in adult mouse epididymis could
      be recovered already from 7-day-old animals. Regional differences appeared at 21
      days of age. These were marked by the secretion of proteins characteristic of the
      proximal (26, 25, 20, 19 kDa) and distal (44, 29 kDa) epididymis. Analysis of
      cytosol and luminal fluid proteins from prepubertal and adult epididymis revealed
      a number of proteins of the same mobility as those synthesized and secreted in
      vitro. Among the luminal proteins which showed variations during development and
      regional differences, four (29, 26, 20, 19 kDa) were characteristics of the
      epididymis and three (88, 34, 13 kDa) comigrated with testicular components.
      Castration or estrogen treatment of prepubertal mice for 4, 3 and 2 weeks
      inhibited or reduced the synthesis of the luminal proteins which appeared during
      postnatal development and/or presented regional differences. Testosterone
      replacement of castrated mice reversed this effect and induced the secretion of
      new proteins (37, 24 kDa).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8143930
TI  - Cells within the bulge region of mouse hair follicle transiently proliferate
      during early anagen: heterogeneity and functional differences of various hair
      cycles.
AB  - Based on cell kinetic, morphological and several biological considerations, we
      have recently proposed that hair follicle stem cells reside in the bulge area of
      the upper follicle. We predicted that during early anagen the normally slow
      cycling bulge stem cells may be activated by the abutting dermal papilla cells to
      undergo transient proliferation giving rise to keratinocytes of the lower
      follicle. In the present work, we performed tritiated thymidine-labeling of DNA
      synthesizing cells and colcemid-arrest of mitotic figures on the skins of 20-23
      and 75-80 day old SENCAR mice, when the follicles entered the anagen phase of the
      2nd and 3rd hair cycles. The results clearly indicate that the normally slow
      cycling bulge cells indeed undergo transient proliferation during early anagen.
      Similar results were obtained when the telogen follicles are experimentally
      induced to enter the 3rd hair cycle by plucking and by topical applications of
      phorbol ester or tretinoin. These results support the notion that bulge cells are
      follicular stem cells, and that transient proliferation of these cells is a
      critical feature of early anagen. However, the long duration of the 2nd telogen
      (> 30 days in mouse) suggests that a new anagen phase does not automatically
      result from the physical proximity of dermal papilla to the bulge cells, and that
      another 'factor' is required for the initiation of the 3rd anagen. The tremendous
      difference in the durations of the first and second telogen (lasting for 2-3 days
      and > 50 days, respectively) suggests that follicles can exist in a non-cycling
      state that may be conceptually equivalent to the G0 state of the cell cycle. Our
      results also underscore the fact that the first hair cycle is distinct from all
      the subsequent hair cycles in their cellular origin and morphological sequence,
      and thus should be regarded as a neogenic event.

PMID- 8143932
TI  - Effects of transforming growth factor beta (TGF beta) and 1,25 dihydroxyvitamin
      D3 on the function, cytochemistry and morphology of normal human osteoblast-like
      cells.
AB  - Individually, transforming growth factor beta (TGF beta) and 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) alter the growth and differentiation of normal
      and transformed osteoblast-like (OB) cells. Although recent evidence suggests
      interactions between TGF beta and 1,25(OH)2D3 may occur, little is known of the
      individual or combined effects of these hormones on the expression of the
      osteoblast phenotype at the cytochemical and biochemical levels in normal human
      OB (hOB) cells. Primary cultures of hOBs were treated with TGF beta (0.001-10
      ng/ml) and 1,25(OH)2D3 (0.1 pM-100 nM) either alone or in combination. TGF beta
      and 1,25(OH)2D3 stimulated spindle-shaped cells to become stellate in appearance
      and increased the number of cytoplasmic processes. TGF beta increased 3H
      thymidine incorporation and 1,25(OH)2D3 reduced this effect. Conversely,
      procollagen type-I synthesis and secretion were increased in a dose-dependent
      manner in the presence of TGF beta but were not significantly affected in the
      presence of 1,25(OH)2D3. TGF beta and 1,25(OH)2D3 each marginally increased
      alkaline phosphatase (ALP) activity, but the combination synergistically
      increased ALP activity in a dose- and time-dependent manner at the cytochemical
      and biochemical level (three to tenfold over vehicle controls; n = 12). In
      contrast, TGF beta reduced 1,25(OH)2D3-stimulated osteocalcin secretion. These
      data suggest that TGF beta stimulates hOB cells to actively produce collagen
      matrix and proliferate. The combination of TGF beta and 1,25(OH)2D3, however,
      produces a synergistic increase in ALP activity and maintenance of collagen
      synthesis. 1,25(OH)2D3 stimulation may induce cells to advance to an endstage
      where cell proliferation is reduced and osteocalcin expression is promoted.
      Interactions between TGF beta and 1,25(OH)2D3 may represent important steps in
      the regulation of osteoblast differentiation and matrix production.

PMID- 8143931
TI  - All-trans-retinoic acid and hexamethylene bisacetamide (HMBA) regulate TGF-alpha
      and Hst-1/kFGF expression in differentiation sensitive but not in resistant human
      teratocarcinomas.
AB  - The multipotent human teratocarcinoma (TC) cell NTera-2 clone D1 (abbreviated
      NT2/D1) differentiates into a neuronal lineage after retinoic acid (RA) treatment
      and a distinct phenotype after hexamethylene bisacetamide (HMBA) treatment. We
      previously reported that RA treatment of NT2/D1 cells reduces cellular cloning
      efficiency and nude mouse tumorigenicity. This accompanied a loss of mRNA
      expression of transforming growth factor-alpha (TGF-alpha) and the fibroblast
      growth factor kFGF, also known as hst-1 (abbreviated hst-1/kFGF). This study
      extends prior work by reporting that the distinct phenotype induced by HMBA also
      decreases cloning efficiency, tumorigenicity, and TGF-alpha and hst-1/kFGF mRNA
      expression in NT2/D1 cells. These RNA findings were confirmed by measurements of
      growth factor protein in the conditioned media of inducer-treated and untreated
      NT2/D1 cells. In two established human TC lines refractory to the actions of RA,
      N2102ep and Tera-1, RA fails to decrease expression of either growth factor
      despite induction of its nuclear receptor, RAR-beta. However, HMBA induces
      morphologic maturation and down-regulation of these growth factors in N2102ep
      cells. This indicates that the loss of TGF-alpha and hst-1/kFGF expression serves
      as a new marker of differentiation in human TCs. To explore the effects of these
      growth factors on growth and differentiation of NT2/D1 cells, TGF-alpha or hst
      1/kFGF protein was added following inducer treatment or no treatment. Neither
      growth factor blocked immunophenotypic differentiation, but both promoted the
      growth of uninduced NT2/D1 cells in cloning assays.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8143933
TI  - Redundant regulatory elements account for the developmental control of a
      ribosomal protein gene of Dictyostelium discoideum.
AB  - In Dictyostelium discoideum, ribosomal protein genes along with other growth
      specific genes appear to be coordinately regulated, primarily in response to
      differences in the translational capacity of developing versus growing cells. In
      particular, expression of the members of this large class of genes is rapidly and
      dramatically deactivated when the developmental program is initiated and growth
      and division cease. In order to understand the mechanisms behind the deactivation
      event and how it is coupled to the transition from growth to development, we have
      analyzed the promoter of the V18 gene, a ribosomal protein gene characteristic of
      this class of growth specific genes. We have delineated three discrete regions
      involved in the transcription and regulation of the V18 gene. A initiator region
      which appears to function in a TATA-independent manner was required for
      transcription and for establishing start site utilization. Two regions upstream
      of this were defined, both of which were found to independently confer proper
      developmental regulation.

PMID- 8143934
TI  - Toward enhanced symbiosis of chemistry and biology.

PMID- 8143935
TI  - Oxalate, germin, and the extracellular matrix of higher plants.
AB  - The article assembles and elaborates evidence which indicates that an 'old'
      enzyme, oxalate oxidase, and an even 'older' substrate, calcium oxalate, have
      significant and previously uncontemplated roles in the biochemistry of the
      extracellular matrix (ECM) of higher plants. These possibilities emerged by
      chance, but not really by chance, when computerized comparisons of amino acid
      sequences inevitably led to the discovery that germin, long known to be a protein
      marker of the onset of growth in germinating wheat, and later known to be an ECM
      protein, is an oxalate oxidase [J. Biol. Chem. 268, 12239-12242 (1993)].
      Dissolution of calcium oxalate, and germin-induced degradation of the resulting
      soluble oxalate, can release Ca2+ and H2O2, both of which are known to have
      central roles in the biochemistry of the ECM in higher plants. It is therefore
      timely to survey the implications of the recent finding that germin is an oxalate
      oxidase in the context of how oxalate may participate not only in the
      biochemistry of the ECM, but in the development of higher plants. The findings
      about oxalate, as a source of H2O2, are a complement to Varner's contemporaneous
      advocacy of a central role for H2O2 in the development, differentiation,
      vascularization and signaling processes of higher plants.

PMID- 8143936
TI  - Appetite and the regulation of body composition.
AB  - Stability of body composition requires that energy intake equals energy
      expenditure when integrated over prolonged periods. As recent human studies have
      failed to demonstrate active changes in energy expenditure with changes in body
      composition, it is likely that energy intake is continually adjusted to preserve
      a constant total adipose tissue mass. If adipose tissue mass is regulated
      directly, then there must be some input reflecting this quantity to the central
      nervous system for the purpose of making corrective changes in appetite when
      total body fat content fluctuates. The nature of this input has been examined in
      a variety of animal experiments involving induced weight change, lipectomy,
      plasma transfer from obese or satiated animals to hungry animals, and parabiosis
      between obese and lean animals. The bulk of evidence suggests that the plasma
      level of one or more currently unidentified stable circulating molecules
      increases in proportion to total body fat content and augments the effect of meal
      related satiety signals in the central nervous system. The implications of this
      adipose tissue-related satiety factor for the pathogenesis of obesity, and the
      possible nature of the factor are discussed.

PMID- 8143937
TI  - What is special about smooth muscle? The significance of covalent crossbridge
      regulation.
AB  - Knowledge of the molecular mechanisms involved in chemomechanical transduction
      and the regulatory elements determining contraction and relaxation are largely
      derived from cross-striated muscle. However, it has become clear that vertebrate
      smooth muscles have features lacking in striated muscle. These derive from
      regulated crossbridge cycling rates observed as variable shortening velocities
      and ATP consumption rates. The special properties of smooth muscle are associated
      with differences in the physiological roles of muscle in the walls of hollow
      organs and reflect a common molecular motor governed by different regulatory
      mechanisms. A remarkably simple scheme involving Ca(2+)-dependent phosphorylation
      of crossbridges in smooth muscle can predict much of the mechanical and
      energetics behavior characterizing the muscle of hollow organs. Nevertheless,
      many unresolved issues are identified that are the focus of current research
      efforts.

PMID- 8143938
TI  - Extracellular ATP in the regulation of renal microvascular function.
AB  - Considerable attention has been focused on the purine nucleoside, adenosine, in
      the control of renal blood flow, epithelial transport, and renin secretion;
      however, surprisingly little attention has been directed toward the renal effects
      of purine nucleotides such as adenosine triphosphate (ATP). Recent studies
      utilizing in vivo micropuncture and in vitro techniques have demonstrated that
      renal vascular, epithelial, and mesangial cells respond to extracellular ATP via
      mechanisms distinct from those elicited by adenosine. ATP vasoconstricts afferent
      but not efferent arterioles whereas adenosine vasoconstricts both vascular
      segments. Adenosine-mediated afferent arteriolar vasoconstriction is abolished by
      adenosine receptor antagonists, whereas the response to ATP is enhanced. ATP
      mediated vasoconstriction reaches a maximum within seconds of exposure while the
      vasoconstriction induced by adenosine develops more slowly. L-type calcium
      channel antagonists such as diltiazem or felodipine prevent the sustained
      afferent vasoconstriction produced by ATP. Data from micropuncture experiments
      indicate that peritubular capillary infusion of ATP reduces glomerular pressure
      and results in marked attenuation of the tubuloglomerular feedback mechanism,
      which transmits signals from the macula densa to the afferent arteriole. These
      data support the existence of ATP-sensitive P2 purinoceptors in the preglomerular
      microvasculature that contribute to the control of renal vascular function via
      activation of calcium channels.

PMID- 8143939
TI  - Structures and functions of collagens in Caenorhabditis elegans.
AB  - Two types of collagens have been identified in Caenorhabditis elegans
      corresponding to two types of extracellular matrix, the cuticle and basement
      membranes. Cuticle collagens are encoded by a developmentally regulated family of
      approximately 100 genes. Mutations in cuticle collagens can produce animals that
      are longer or shorter than normal and/or that are helically twisted. Mutations in
      different collagens can cause different morphological abnormalities, as can
      different mutations in the same collagen. Genetic interactions between collagen
      genes have been described and may identify collagens that interact to form the
      cuticle. Two basement membrane (type IV) collagen genes have been identified in
      C. elegans. They encode proteins similar in structure to vertebrate type IV
      collagen. One of the genes produces two alternatively spliced forms, one
      predominantly expressed in embryos and the other in larvae and adults, suggesting
      that embryonic basement membranes may have unique properties. Most mutations in
      the type IV genes cause embryonic lethality, indicating that normal basement
      membranes are required for embryogenesis. Temperature-sensitive mutations have
      been used to show that type IV collagen function is also required for larval
      development and adult fertility.

PMID- 8143940
TI  - Modulation of steroid receptor-mediated gene expression by vitamin B6.
AB  - Gene transcription mediated by steroid hormones has become one of the most
      extensively characterized model systems for studying the regulation of gene
      expression in eukaryotic cells. However, specific details of gene regulation by
      steroid hormones are often complex and may be unique in specific cell types.
      Diverse regulatory mechanisms leading to either activation or repression of
      particular genes frequently involve interactions between steroid hormone
      receptors and other ubiquitous and/or cell-specific transcription factors that
      act on the complex promoter of the regulated gene. Interplay between steroid
      receptor-mediated and other signal transduction pathways may also be involved. In
      addition, recent novel results indicate that moderate variations in the
      intracellular concentration of pyridoxal 5'-phosphate (PLP), the biologically
      active form of vitamin B6, can have pronounced modulatory effects on steroid
      induced gene expression. Specifically, elevation of intracellular PLP levels
      leads to decreased transcriptional responses to glucocorticoid, progesterone,
      androgen, or estrogen hormones. Conversely, cells in a vitamin B6-deficient state
      exhibit enhanced responsiveness to steroid hormones. One aspect of the mechanism
      by which these transcriptional modulatory effects of PLP occur has recently been
      shown to involve interruption of functional interactions between steroid hormone
      receptors and the nuclear transcription factor NF1. These findings--that the
      vitamin B6 nutritional status of cells modulates their capacity to respond to
      steroid hormones--impose an additional level of cell-specific control over
      steroid hormone regulation of gene expression and will serve as the focal point
      for this review.

PMID- 8143941
TI  - Role of the mouse in the delineation of the anabolic-androgenic action of
      steroids.

PMID- 8143942
TI  - [Endoscopy, treatment of the future in chronic pancreatitis?].

PMID- 8143943
TI  - Effects of proglumide and enprostil on omeprazole-induced fundic endocrine cell
      hyperplasia in rats.
AB  - Long-term treatment with omeprazole induces hyperplasia of enterochromaffin-like
      cells, closely related to hypergastrinemia. We studied whether proglumide, an
      antagonist of gastrin/CCK receptor, and enprostil, a synthetic prostaglandin E2
      derivative, might inhibit this hyperplasia. Six groups of 8 rats were treated for
      10 weeks: a) untreated controls; b) omeprazole 10 mumol/kg; c) proglumide 500
      mg/kg; d) enprostil 30 micrograms/kg; e) association of omeprazole and
      proglumide; f) association of omeprazole and enprostil. Serum gastrin levels were
      measured at different times during treatment. After sacrifice, fundic argyrophil
      cells were assessed by Grimelius' staining. Serum gastrin levels and argyrophil
      cell density were not modified in proglumide- and enprostil-treated groups, as
      compared with controls. Omeprazole increased significantly these two parameters.
      When given with omeprazole, proglumide decreased significantly serum gastrin
      levels and argyrophil cell density, as compared to omeprazole alone, while
      enprostil did not modify significantly these two parameters. These results
      indicate that proglumide, but not enprostil, can counteract the omeprazole
      induced argyrophil cell hyperplasia in rats.

PMID- 8143944
TI  - [Endoscopic treatment and extracorporeal lithotripsy in chronic calcifying
      pancreatitis. Preliminary results in 16 patients].
AB  - A new therapeutic approach has been recently proposed in the management of
      chronic pancreatitis, including pancreatic endoscopic papillotomy and
      extracorporeal shock wave lithotripsy. The aim of this study was to assess the
      feasibility and the short--and long-term results of these procedures in a series
      of 16 patients aged 48.9 +/- 14 years. The indication for endoscopic treatment
      was pain in 15 cases and steatorrhea in one case. Pancreatic duct abnormalities
      included main pancreatic duct stenosis with calculi (9 cases), communicating
      pseudocysts upstream to a ductal stenosis or obstruction by calculi (4 cases),
      and isolated calculi (4 cases). Clinical response and morphologic parameters were
      used for analysis. Mean follow-up was 18.6 months (3.5 months to 7 years).
      RESULTS: a) pancreatic endoscopic papillotomy, stents placement, and
      extracorporeal shock wave lithotripsy were successfully performed in 15 out of 16
      cases, 1 out of 4 cases and 8 out of 8 cases, respectively; b) symptomatic
      improvement was observed in 11 of 15 patients with painful pancreatitis as relief
      was complete in 8, and partial in 3 cases. Pain relapse occurred in these latter
      3 patients 4, 18 and 48 months after treatment; diabetes mellitus remained
      unchanged in all cases; c) diameter of the main pancreatic duct and pancreatic
      calcifications decreased in 8 of 15 cases and in 10 of 15 cases, respectively;
      pseudocyst disappeared in 2 of 4 cases; clinical improvement was significantly
      correlated with pancreatic morphology improvement. Clinical relapse was
      associated with calculi recurrence in every case. No complication was observed.
      Endoscopic papillotomy and extracorporeal shock wave lithotripsy are feasible in
      most cases of chronic pancreatitis. Relief of pain is obtained rapidly after
      treatment and seems to be correlated with the quality of pancreatic drainage.

PMID- 8143945
TI  - [Endoscopic drainage of pseudocysts of the pancreas. Study of 26 cases].
AB  - Endoscopic drainage of pancreatic pseudocysts has been proposed for several years
      as an alternative to surgical treatment. We report the results of 26 endoscopic
      cystostomies of pancreatic pseudocysts (13 cystoduodenostomies, 13
      cystogastrostomies) performed in two specialized centres, from 1985 to 1991. The
      patients were divided into 3 groups (I, II, III) according to the pseudocysts'
      clinical presentation. The opening of the collection into digestive lumen was
      achieved in 22 cases; there were 3 puncture failures and 1 cystostomy was not
      performed because of a prior haemorrhagic puncture. Pain relief was obtained
      rapidly after cystodigestive drainage in 13 out of the 14 symptomatic patients.
      Three complications required surgery: 1 bleeding after cystoduodenostomy, 1
      perforation and 1 peritonitis after cystogastrostomies. Two of them occurred
      after recutting a cystostomy. Two pseudocyst surinfections healed with antibiotic
      therapy. No deaths occurred due to the procedure. Among the 18 long-term followed
      up patients (average = 33 months), 4 required surgery for persistence or relapse
      of pseudocysts. The results were excellent for the 14 other patients without any
      difference between cystoduodenostomies and cystogastrostomies, neither between
      the I, II and III groups. Each of the 5 cases with a digestive lumen-pseudocyst
      cavity thickness above 1 cm (measured on 20 CT scans) failed: 1 puncture failure,
      3 complications, 1 relapse.

PMID- 8143946
TI  - [What is the prognosis in unclassified colitis? Results of a cohort study of 104
      patients in the Northern-Pas-de-Calais region].
AB  - Acute unclassified colitis could be the first attack of inflammatory bowel
      disease, particularly chronic ulcerative colitis or acute non specific colitis
      regarded as being of infectious origin without recurrence. The aim of this work
      was to determine the outcome of 104 incidental cases of acute unclassified
      colitis diagnosed during the year 1988 at a census point made 2.5 to 3 years
      later and to search for demographic and clinical discriminating data for final
      diagnosis. Thirteen patients (12.5%) were lost to follow up. Another final
      diagnosis was made in three other patients: two had salmonellosis and one
      diverticulosis. Of the remaining 88 patients, 46 (52.3%) relapsed and were
      subsequently classified as inflammatory bowel disease: 54% ulcerative colitis,
      33% Crohn's disease and 13% chronic unclassified colitis. Forty-two (47.7%) did
      not relapse and were considered to have acute non specific colitis. The mean age
      at onset was significantly lower in patients with inflammatory bowel disease
      (32.3 years) than in patients with acute non specific colitis (42.6 years) (P <
      0.001). No clinical data (diarrhea, abdominal pain, bloody stool, mucus discharge
      fever, weight loss) was predictive of the final diagnosis. In this series, 52.3%
      of patients initially classified as having an acute unclassified colitis had a
      final diagnosis of inflammatory bowel disease after a 2.5-3 years follow-up.
      These data warrant a thorough follow up of acute unclassified colitis, especially
      when it occurs in patients < 40 years.

PMID- 8143947
TI  - [Treatment of exocrine pancreatic insufficiency: what gastroprotection do
      pancreatic enzymes provide?].

PMID- 8143948
TI  - [Shortage of hepatic grafts: which solutions to face the unavoidable?].

PMID- 8143949
TI  - [Indications and results of liver transplantation for hepatocellular carcinoma.
      Retrospective study in 17 patients].
AB  - Orthotopic liver transplantation has been considered as one of the therapeutic
      tools in certain patients with hepatocellular carcinoma. In our liver Unit in
      Besancon, 17 patients with hepatocellular carcinoma were treated by orthotopic
      liver transplantation between March 1986 and December 1991. This series included
      14 men and 3 women. The mean age was 51 years (range: 36-62). In 11 cases,
      hepatocellular carcinoma was multifocal and larger than 5 cm, in 6 cases, the
      tumor was encapsulated, and was well differentiated in 11 cases. Lymph node
      invasion was observed in 2 cases and the portal vein was invaded in 5 cases.
      Before orthotopic liver transplantation, alpha foetoprotein was increased in 10
      cases. Kaplan-Meier actuarial survival was 76%, 53%, 40%, at one, two and three
      years, respectively, and remained unchanged at four years. There were 9
      recurrences of hepatocellular carcinoma. There were 8 deaths, 4 due to a tumor
      recurrence. A tumor larger than 5 cm was the only parameter statistically
      associated with recurrence in this study.

PMID- 8143950
TI  - [Elective cholecystectomy by celioscopy versus subcostal approach
      cholecystectomy. Comparative study of postoperative pain and discomfort].
AB  - The aim of this prospective study was to evaluate postoperative pain and
      discomfort in 70 patients undergoing cholecystectomy. The choice of surgical
      approach was left to the surgeon. Accordingly, these patients were then divided
      in two groups: laparoscopic cholecystectomy (group I; n = 37); classic
      cholecystectomy (subcostal incision) (group II; n = 33). There was no significant
      difference between these groups concerning weight/height ratio, size and number
      of stones. Patients in group II were older (55 +/- 16 years) than those in group
      I (46 +/- 11 years) (P < 0.01). The mean duration of surgery was shorter in group
      II (96 +/- 31 min) than in group I (119 +/- 49 min) (P < 0.01). Postoperative
      discomfort was evaluated by (group I versus group II respectively): a) the mean
      length of hospital stay after surgery (3.7 +/- 1.5 versus 6.7 +/- 1.1 days, P <
      0.02); b) the mean delay to return of intestinal motility (1.5 +/- 0.6 versus 2.0
      +/- 0.6 days, P < 0.001); c) the mean perfusion time (1.4 +/- 0.6 versus 2.6 +/-
      0.8 days, P < 0.001); d) intensity of postoperative pain which was evaluated
      daily. There was no significant difference between these two groups concerning
      the use of analgesics; however, a statistically significant difference was found
      in the visual and verbal scales, starting on the second postoperative day and in
      autonomy as early as the first postoperative day.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8143951
TI  - [Ultrasound study of gallbladder motility in healthy subjects. Reproducibility of
      the method and effect of alcohol].
AB  - The protective effect of alcohol against cholesterol cholelithiasis has been
      established in several epidemiologic studies. An impairment of gallbladder
      motility in gallstone disease has been demonstrated in animals and in man. At a
      daily dose of 39 g, alcohol reduces the lithogenic index of bile, but its effect
      on gallbladder motility is still debated. To test this potential mechanism, the
      effect of 20 g of alcohol on gallbladder motility was studied, using an
      ultrasonographic ellipsoid method in 16 healthy male subjects. The stimulus for
      gallbladder contraction was a Lundh test meal. Using a cross over method, this
      meal was ingested by each subject once with water and once with alcohol. A third
      set of measurements was taken in each subject after ingestion of a Lundh meal and
      water to test the reproducibility of the sonographic method. The gallbladder
      kinetics were studied for 90 minutes following ingestion of the test meal and
      beverage. Alcohol stimulated rapid post prandial gallbladder emptying, and
      accelerated gallbladder filling. This second action could result from sphincter
      of Oddi pressure enhancement and, perhaps, decrease of gallbladder absorption by
      Na+ K+ ATPase inhibition. The reproducibility of the method was good. With a
      decrease of lithogenic bile index, the protective effect of alcohol against
      biliary cholesterol cholelithiasis could be due either to stimulation of
      gallbladder emptying and/or acceleration of gallbladder filling.

PMID- 8143952
TI  - [All out search of graft for liver transplantation].

PMID- 8143953
TI  - [Pseudotumoral hyperplasia of Brunner's glands].
AB  - Hyperplasia of Brunner's glands is a dysembryoplastic or hyperplasic lesion with
      an elective location of the proximal duodenum. Symptoms are often non-specific
      but severe manifestations can occur (haemorrhage, duodenal obstruction). Two
      cases of hyperplasia of Brunner's glands were reported due to their particularly
      large size and a misguiding clinical appearance. Difficulties in diagnosis due to
      this rare benign entity were discussed.

PMID- 8143954
TI  - [Ileocolitis caused by Herpes simplex virus type 2].
AB  - The authors report the case of a 51-year-old woman who was hospitalized for
      severe acute colitis. Sub-total colectomy was performed, due to clinical
      deterioration and resistance to treatment. The examination of the surgery
      specimen revealed a herpes-virus type 2 as the responsible pathogen agent.
      Complementary aciclovir treatment cured the patient.

PMID- 8143955
TI  - [Ciliated cysts of the liver. 2 cases].
AB  - We report herein two cases of ciliated hepatic cysts. These exceptional lesions
      belong to the category of solitary nonparasitic cysts. They are probably
      dysembryoplastic and appear to derive from the embryonic foregut. Diagnosis is
      based on microscopic examination of the surgical specimen. The role of aspiration
      cytology in the preoperative diagnosis of this lesion has not yet been defined.

PMID- 8143956
TI  - [Veno-occlusive disease after liver transplantation. Association of acute
      cellular rejection and toxicity of azathioprine].
AB  - Azathioprine vascular hepatotoxicity has been described mainly after renal
      transplantation. We report a new case in a patient who developed veno-occlusive
      disease of the liver 3 weeks after liver transplantation; regression of lesions
      were observed after discontinuation of azathioprine therapy. In this case,
      azathioprine hepatotoxicity may have been enhanced by a previous episode of
      severe, acute rejection prevailing in the hepatic veins. After liver
      transplantation, the diagnosis of azathioprine hepatotoxicity is difficult but
      should be suspected in the presence of non-inflammatory small hepatic veins
      lesions. Early withdrawal of the drug is mandatory for complete recovery.

PMID- 8143957
TI  - [Esophageal mycosis during primary human immunodeficiency virus infection].

PMID- 8143958
TI  - [Endoscopic injections of ethanol in the treatment of dysphagia related to
      esophageal carcinoma: efficacy and tolerance in 16 patients].

PMID- 8143959
TI  - [Treatment by extracorporeal lithotripsy of a patient with chronic pancreatitis].

PMID- 8143960
TI  - [Rectovaginal fistula after prolonged intake of suppositories containing
      dextropropoxyphene and paracetamol (Di-Antalvic)].

PMID- 8143961
TI  - [Bilioportal fistula caused by closed trauma of the liver].

PMID- 8143962
TI  - [Icterus and irrepressible vomiting during pregnancy].

PMID- 8143963
TI  - [Spontaneous infection of ascitic fluid caused by Yersinia pseudotuberculosis
      revealing probable genetic hemochromatosis].

PMID- 8143964
TI  - [Diffusion of cefpirome in ascitic fluid].

PMID- 8143965
TI  - [Is the therapeutic combination of pancreatic endoscopic sphincterotomy and
      extracorporeal lithotripsy effective in the treatment of calculi of Wirsung's
      duct?].

PMID- 8143966
TI  - [Cancer of the gallbladder: status of 1977-1986].

PMID- 8143967
TI  - A long-term follow-up study of asymptomatic hepatitis B surface antigen-positive
      carriers in Montreal.
AB  - BACKGROUND/AIMS: Prospective studies from the Far East and Alaska have shown an
      increased mortality from cirrhosis and/or hepatocellular carcinoma in
      asymptomatic hepatitis B virus (HBV) carriers. The magnitude of this risk in
      apparently healthy North American carriers remains undefined. METHODS: The
      outcomes of 317 asymptomatic hepatitis B surface antigen-positive carriers from
      the Montreal area were examined after 16 years of follow-up. A majority of
      carriers were of French Canadian origin, were positive for antibody to hepatitis
      B e antigen, and had normal serum transaminase levels; institutionalization in
      orphanages as infants or children was the most important epidemiological risk
      factor, suggesting horizontal transmission of HBV during childhood. RESULTS: At
      follow-up, mean age was 46 +/- 8 years; 3 carriers had died of HBV-related
      cirrhosis, 1 of alcoholic cirrhosis, and 9 of causes unrelated to liver disease.
      No carrier died of hepatocellular carcinoma; had the risk of hepatocellular
      carcinoma been similar to that reported from the Far East and Alaska, 17 cases of
      hepatocellular carcinoma-related deaths would have been expected. During follow
      up, the annual negativation rate for hepatitis B surface antigen was 0.7%.
      CONCLUSIONS: In asymptomatic HBV carriers from Montreal, a majority are "healthy"
      carriers and remain asymptomatic after 16 years of follow-up and the risk of
      death from HBV-related cirrhosis and/or hepatocellular carcinoma is low.

PMID- 8143968
TI  - Altered control of vascular tone by adenosine triphosphate-sensitive potassium
      channels in rats with cirrhosis.
AB  - BACKGROUND/AIMS: Because the activation of arterial adenosine triphosphate (ATP)
      sensitive potassium (KATP) channels is known to induce vasodilation, these
      channels may contribute to baseline vasodilator tone in cirrhosis. This study
      aimed to examine hemodynamic responses to glibenclamide, a KATP channel blocker,
      and to aprikalim, a vasodilator activating KATP channels, in normal and cirrhotic
      rats. METHODS: Splanchnic and systemic hemodynamic responses to glibenclamide
      (2.5, 5, 20, 30 mg/kg, intravenously) were studied. The arterial pressure
      response to aprikalim (200 mu/kg, intravenously) was studied with and without
      glibenclamide pretreatment (20 mg/kg). RESULTS: In cirrhotic rats, glibenclamide
      (5, 20, 30 mg/kg but not 2.5 mg/kg) significantly increased vascular resistance
      in portal and systemic territories. In normal rats, the latter effects occurred
      with 20 and 30 mg/kg of glibenclamide only. Aprikalim-induced arterial
      hypotension was significantly less marked in cirrhotic than in normal rats.
      Following glibenclamide, aprikalim-induced arterial hypotension was significantly
      less marked in cirrhotic than in normal animals. CONCLUSIONS: In rats with
      cirrhosis, the glibenclamide-induced vasoconstriction indicates that a
      vasodilator tone due to KATP channel opening existed under baseline conditions.
      Moreover, this study suggests that the control of vascular tone by KATP channels
      is altered in cirrhosis.

PMID- 8143969
TI  - Increased spermidine or spermine level is essential for hepatocyte growth factor
      induced DNA synthesis in cultured rat hepatocytes.
AB  - BACKGROUND/AIMS: Hepatocyte growth factor is a potent mitogen for mature
      hepatocytes and seems to act as a trigger for liver regeneration. Hepatocyte
      growth factor was first purified from human and rabbit plasma and rat platelets.
      Additionally, putrescine, spermidine, and spermine are widely distributed in many
      different cells; intracellular concentrations of these polyamines are closely
      related to cell proliferation. The present study examined whether polyamine
      metabolism is involved in hepatocyte growth factor-induced DNA synthesis in
      primary cultured rat hepatocytes. METHODS: Hepatocytes were isolated from rats by
      the collagenase perfusion method. Ornithine decarboxylase and S
      adenosylmethionine decarboxylase activities were measured as the release of 14CO2
      from L-[1-14C]ornithine and S-adenosyl-L-[carboxyl-14C]methionine, respectively.
      RESULTS: alpha-Difluoromethylornithine inhibited hepatocyte growth factor-induced
      DNA synthesis by only 21%. On the other hand, methylglyoxal bis(guanylhydrazone)
      completely inhibited hepatocyte growth factor-induced DNA synthesis to nontreated
      control level. The inhibitory effect of methylglyoxal bis(guanylhydrazone) on
      hepatocyte growth factor-induced DNA synthesis was reversed by exogenously added
      spermidine or spermine. CONCLUSIONS: Spermidine or spermine is essential for
      hepatocyte growth factor-induced DNA synthesis in primary cultured rat
      hepatocytes.

PMID- 8143970
TI  - The changing scene of hepatic vein thrombosis: recognition of asymptomatic cases.
AB  - BACKGROUND/AIMS: Hepatic vein thrombosis is thought to be manifested by ascites,
      abdominal pain, and hepatomegaly, with a uniformly poor prognosis. However, new
      imaging techniques allow for the diagnosis of hepatic vein thrombosis in
      asymptomatic cases. The aim of our study was to re-evaluate symptoms and
      prognosis in patients with hepatic vein thrombosis. METHODS: Eighty-one patients
      with hepatic vein thrombosis were analyzed. Forty-seven patients were admitted
      from 1970 to June 1987 (group I, before Doppler ultrasonography and magnetic
      resonance imaging were introduced at our hospital) and 34 from July 1987 to June
      1991 (group II). RESULTS: When comparing the two groups, age, sex ratio, and
      causes of hepatic vein thrombosis did not differ. Eight group II patients
      (asymptomatic patients) had no ascites, hepatomegaly, or abdominal pain. One
      major hepatic vein remained patent in 41% of group II patients, compared with 12%
      in group I (P < 0.05). Intrahepatic collaterals were seen in 79% of group II
      patients, compared with 21% of group I patients (P < 0.01). All asymptomatic
      patients had large intrahepatic and portasystemic collaterals. At 3 years, death
      occurred in 22% of group II patients and in 45% of group I patients. No
      asymptomatic patient died. CONCLUSIONS: Asymptomatic hepatic vein thrombosis is
      associated with the spontaneous development of large intrahepatic and
      portosystemic collaterals. In asymptomatic patients, prognosis at 3 years seems
      to be good, and surgical therapy may not be required.

PMID- 8143971
TI  - Displacement of hepatitis B virus by hepatitis C virus as the cause of continuing
      chronic hepatitis.
AB  - BACKGROUND/AIMS: It has been shown that hepatitis C virus (HCV) superinfection
      may suppress hepatitis B virus (HBV) leading to hepatitis B surface antigen
      (HBsAg) clearance and that hepatitis may persist after HBsAg clearance in a few
      patients. The role of HCV in continuing hepatitis after termination of chronic
      HBsAg antigenemia remains to be explored in a series of patients. METHODS: HCV
      markers were studied using second generation enzyme immunoassay and polymerase
      chain reaction with reverse transcription and were compared between 41 patients
      with persistent alanine aminotransferase (ALT) elevation (hepatitis group) and 82
      age/sex-matched patients with normal ALT (control group) after HBsAg clearance.
      RESULTS: Twenty-six (63%) of the 41 hepatitis group patients were seropositive
      for antibodies to HCV (anti-HCV) compared with only 4 (5%) of 82 controls (P <
      0.0001). Six patients of the hepatitis group and 1 control had an episode of
      acute hepatitis C with seroconversion of anti-HCV 1-68 months before HBsAg
      clearance. Of those seropositive for anti-HCV, serum HBV DNA was not detectable,
      and serum HCV RNA was detected in 23 (88.5%) of the 26 hepatitis patients but
      none of the 4 controls (P < 0.001). Liver biopsy in 6 anti-HCV positive patients
      with continuing hepatitis showed features compatible with chronic hepatitis C.
      HCV RNA, but not HBV DNA, was detected in liver tissues of these 6 patients.
      CONCLUSIONS: The results suggest that HCV may usurp the role of HBV in chronic
      hepatitis and act as the major cause of continuing hepatitis or ALT elevation
      after HBV/HBsAg clearance.

PMID- 8143972
TI  - Altered expression of MUC2, MUC4, and MUC5 mucin genes in pancreas tissues and
      cancer cell lines.
AB  - BACKGROUND/AIMS: Neoplastic transformation of epithelial cells is commonly
      associated with altered synthesis and structure of mucin glycoproteins. The aim
      of the study was to determine if altered mucin gene expression takes place in
      pancreas cancer. METHODS: To examine mucin gene expression in normal pancreas and
      pancreas cancer, antibodies detecting the MUC1, MUC2, MUC5B, and MUC5C apomucins
      were used in immunohistochemical techniques and complementary DNA probes specific
      for the MUC1-MUC5 genes were used in Northern blots. RESULTS: MUC1 is the major
      apomucin expressed in normal pancreas, whereas MUC2-MUC5 are weakly expressed or
      undetectable. In pancreas cancer tissues and cell lines, increased expression of
      MUC2, MUC4, and MUC5C is shown. The cytoplasmic expression of MUC2 and MUC5C in
      tumor cells suggests that these apomucins are underglycosylated and abnormally
      compartmentalized. CONCLUSIONS: Enhanced expression of MUC2, MUC4, and MUC5C
      genes is a frequent event in pancreas cancer and may contribute to the
      alterations in the biochemical structure of pancreas cancer mucins.

PMID- 8143973
TI  - Diagnosis of choledocholithiasis by endoscopic ultrasonography.
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography is a promising procedure for the
      diagnosis of extrahepatic cholestasis. Accuracy for the diagnosis of
      choledocholithiasis by ultrasonography and computed tomography were prospectively
      compared with endoscopic ultrasonography in 62 consecutive patients. METHODS:
      Final diagnosis was determined by endoscopic retrograde cholangiography with or
      without sphincterotomy or intraoperative cholangiography with or without
      choledochoscopy. All of the patients had abdominal ultrasonography, computed
      tomography, endoscopic ultrasonography, and either an endoscopic retrograde (n =
      40) or intraoperative cholangiography (n = 32) performed. RESULTS:
      Choledocholithiasis was confirmed in 22 patients. Thirteen patients had a stone
      with a diameter < 1 cm, and 14 had a nonenlarged common bile duct. Endoscopic
      ultrasonography was more sensitive (97%) than ultrasonography (25%; P < 0.0001)
      and computed tomography (75%; P < 0.02). Specificity and positive predictive
      value were not significantly different. Negative predictive value of endoscopic
      ultrasonography (97%) was better than that of ultrasonography (56%; P < 0.0001)
      and computed tomography (78%; P < 0.02). Results were unchanged after six
      patients in whom the absence of choledocholithiasis was considered probable after
      follow-up were excluded. Endoscopic ultrasonography results did not depend on
      stone diameter or common bile duct dilatation. CONCLUSIONS: Endoscopic
      ultrasonography appears to be the best diagnostic tool for the diagnosis of
      choledocholithiasis compared with other noninvasive procedures.

PMID- 8143974
TI  - Dystonia, hyperintense basal ganglia, and high whole blood manganese levels in
      Alagille's syndrome.
AB  - Hyperintensity of the globus pallidus on T1-weighted magnetic resonance imaging
      (MRI) has been reported in patients with chronic liver disease. This abnormality
      has been associated with the severity of liver disease and tremor, but its cause
      is unknown. Similar MRI signal abnormalities have been reported in experimental
      models of manganese neurotoxicity. This case report describes a child with
      Alagille's syndrome and end-stage liver disease who developed dystonia and tremor
      associated with an elevated whole blood manganese level and symmetric
      hyperintense globus pallidi and subthalamic nuclei on T1-weighted but not T2
      weighted MRI. Liver transplantation was performed; 2 months later, neurological
      function was improved, manganese levels were normal, and the MRI signal
      abnormality had completely resolved. This child had neurological findings
      described in manganese neurotoxicity with compatible laboratory and radiological
      findings. Manganese is excreted by the liver in bile, and toxicity may have
      resulted from the inadequacy of this mechanism, subsequently corrected by liver
      transplantation.

PMID- 8143975
TI  - Hypervariable region of hepatitis C virus envelope glycoprotein (E2/NS1) in an
      agammaglobulinemic patient.
AB  - In an agammaglobulinemic patient with chronic hepatitis C, a previously
      identified hypervariable region of the major envelope glycoprotein remained
      unchanged for 2.5 years. Serum-derived RNA amplified by reverse transcription
      polymerase chain reaction was cloned in a bacterial vector, and a minimum of
      three independent clones were sequenced by dideoxy chain termination reaction.
      Comparison of consensus sequences from three different time points during the
      chronic phase of infection showed absolute homology at both amino acid and
      nucleotide levels. This finding provides support for the role of antibody
      selection in generating genetic variation and viral persistence; also, it is
      consistent with the hypothesis that an epitope within this region is the site of
      virus neutralization. The observations show that the hepatitis seen in hepatitis
      C virus infection is not dependent on the humoral immune response.

PMID- 8143976
TI  - Gene therapy: applications to the treatment of gastrointestinal and liver
      diseases.
AB  - There has been much progress in our understanding of molecular mechanisms in the
      pathogenesis of inherited metabolic disorders. In addition, powerful new
      molecular techniques have made possible phenotypic alterations by delivery of
      foreign genes to target cells. As a result, concepts and methods that would have
      been considered purely science fiction 10 years ago can now be found in human
      clinical trials engaged in the treatment of these disorders. In this review, we
      have attempted to provide an introduction and survey of the topic of gene
      therapy, with specific examples of laboratory and clinical achievements to date,
      and highlights on potentials for applications in digestive diseases.

PMID- 8143977
TI  - Alcohol and the liver: 1994 update.
AB  - This article reviews current concepts on the pathogenesis and treatment of
      alcoholic liver disease. It has been known that the hepatotoxicity of ethanol
      results from alcohol dehydrogenase-mediated excessive generation of hepatic
      nicotinamide adenine dinucleotide, reduced form, and acetaldehyde. It is now
      recognized that acetaldehyde is also produced by an accessory (but inducible)
      microsomal pathway that additionally generates oxygen radicals and activates many
      xenobiotics to toxic metabolites, thereby explaining the increased vulnerability
      of heavy drinkers to industrial solvents, anesthetics, commonly used drugs, over
      the-counter medications, and carcinogens. The contribution of gastric alcohol
      dehydrogenase to the first-pass metabolism of ethanol and alcohol-drug
      interactions is discussed. Roles for hepatitis C, cytokines, sex, genetics, and
      age are now emerging. Alcohol also alters the degradation of key nutrients,
      thereby promoting deficiencies as well as toxic interactions with vitamin A and
      beta carotene. Conversely, nutritional deficits may affect the toxicity of
      ethanol and acetaldehyde, as illustrated by the depletion in glutathione,
      ameliorated by S-adenosyl-L-methionine. Other "supernutrients" include
      polyunsaturated lecithin, shown to correct the alcohol-induced hepatic
      phosphatidylcholine depletion and to prevent alcoholic cirrhosis in nonhuman
      primates. Thus, a better understanding of the pathology induced by ethanol is now
      generating improved prospects for therapy.

PMID- 8143978
TI  - Accelerated healing of duodenal ulcers by oral administration of a mutein of
      basic fibroblast growth factor in rats.
AB  - BACKGROUND/AIMS: Human basic fibroblast growth factor (bFGF) is an endothelial
      mitogen that stimulates angiogenesis and proliferation of other cells such as
      fibroblasts and smooth muscle cells. After this peptide was stabilized to acid
      and pepsin by site-specific mutagenesis, it was tested whether bFGF might
      accelerate the healing of experimental duodenal ulcers. METHODS: This mutein
      peptide (bFGF-CS23) was administered orally in comparison with cimetidine to rats
      with chronic duodenal ulcers previously induced by cysteamine. RESULTS: Oral bFGF
      CS23 therapy maintained for 21 days at 100 ng/100 g twice daily resulted in (1)
      significant acceleration of healing of duodenal ulcers, i.e., reduction of mean
      ulcer area by 83% in the bFGF-CS23-treated rats compared with only 61% for
      cimetidine therapy and 40% for untreated controls; (2) complete healing with no
      residual ulcer in 62% of the bFGF-CS23-treated rats compared with only 7% of
      untreated rats; and (3) a ninefold increase in angiogenesis in the ulcer bed
      compared with untreated controls. A single dose of the bFGF-CS23 mutein had no
      effect on gastric output of hydrochloric acid or pepsin, but daily treatment for
      2 or 3 weeks resulted in enhanced acid and pepsin outputs. CONCLUSIONS: Chronic
      duodenal ulcers can be healed rapidly by stimulating angiogenesis and other wound
      healing processes in the ulcer bed without reduction of gastric acid.

PMID- 8143979
TI  - The clinical pharmacology of motility disorders: the perils (and pearls) of
      prokinesia.

PMID- 8143980
TI  - Functional gastrointestinal disease and the autonomic nervous system: a way
      ahead?

PMID- 8143981
TI  - Hepatitis C virus pathogenicity: the corner pieces of the jigsaw puzzle are
      found.

PMID- 8143982
TI  - Big and tall: protective against colorectal cancer?

PMID- 8143983
TI  - Specific regulation of a mucosal addressin.

PMID- 8143984
TI  - Role of cathepsin B in the pathogenesis of acute pancreatitis.

PMID- 8143985
TI  - Dysplastic Barrett's: is continued surveillance appropriate?

PMID- 8143986
TI  - Surveillance for ulcerative colitis does not and cannot work.

PMID- 8143987
TI  - Low-dose captopril for patients with liver cirrhosis: what is low?

PMID- 8143988
TI  - Can esophageal physiology predict anatomy?

PMID- 8143989
TI  - Reciprocal expression of laminin A-chain isoforms along the crypt-villus axis in
      the human small intestine.
AB  - BACKGROUND/AIMS: Intestinal epithelial cell proliferation, migration, and
      differentiation are susceptible to various influences along the crypt-villus axis
      including compositional changes in the basement membrane and differential
      expression of receptors for these components. However, laminin has been
      consistently detected at the epithelial basement membrane without significant
      variation in relation to the crypt-villus functional unit. The aim of this study
      was to examine the distribution of individual laminin chains. METHODS: The
      patterns of distribution of laminin A, M (an A-chain variant), B1, and B2 chains
      as well as the integrins alpha 6 beta 1 and alpha 6 beta 4, two laminin
      receptors, were determined by indirect immunofluorescence in the adult human
      small intestine. RESULTS: Markedly distinct patterns of laminin chain expression
      were observed along the crypt-villus axis. The A chain was found predominantly
      associated with the differentiated epithelial cells on the villus whereas the M
      chain was restricted to the basement membrane of crypts. However, both B1 and B2
      chains were detected all along the intestinal basement membrane. Furthermore,
      alpha 6 beta 1 and alpha 6 beta 4 integrins were found to be expressed by all
      enterocytes. CONCLUSIONS: These observations show a reciprocal expression of
      laminin isoforms along the crypt-villus axis and support the concept that the
      intestinal epithelial basement membrane is subjected to intricate compositional
      changes.

PMID- 8143990
TI  - Platelets circulate in an activated state in inflammatory bowel disease.
AB  - BACKGROUND/AIMS: Platelets show proinflammatory as well as prothrombotic
      properties. Patients with inflammatory bowel disease are at increased risk of
      systemic thromboembolism, and multifocal microvascular infarction has been
      proposed as a pathogenetic mechanism in Crohn's disease. The aim of this study
      was to determine if inflammatory bowel disease is associated with abnormal
      platelet behavior. METHODS: Platelet activation and aggregability were assessed
      using flow cytometry, Born aggregometry, and the modified method of Wu and Hoak.
      Serum beta-thromboglobulin was measured in patients with Crohn's disease and
      ulcerative colitis and, as controls, in healthy volunteers and patients with
      active rheumatoid arthritis. RESULTS: Platelet surface expression of P-selectin
      and GP53 (markers of activation) were increased in Crohn's disease (13 of 30
      patients abnormal for P-selectin; 9 of 28 abnormal for GP53) (P < 0.01) and
      ulcerative colitis (9 of 21 for P-selectin; 10 of 21 for GP53) (P < 0.01)
      compared with healthy controls. Increased circulating platelet aggregates (15 of
      24 patients with Crohn's disease and 8 of 16 with ulcerative colitis) (P < 0.01),
      platelet aggregability in vitro, and serum beta-thromboglobulin were detected in
      active inflammatory bowel disease compared with healthy controls. Platelet
      behavior in active rheumatoid arthritis resembled that in healthy controls.
      CONCLUSIONS: Increased platelet activation and aggregation are features of
      inflammatory bowel disease and may contribute to the risk of systemic
      thromboembolism and the pathogenesis of mucosal inflammation. Therefore,
      antiplatelet agents may be valuable in the management of inflammatory bowel
      disease.

PMID- 8143991
TI  - Gastrointestinal lymphoma in adults: clinical features and management of 300
      cases.
AB  - BACKGROUND/AIMS: Gastrointestinal lymphoma is a rare disease. A study was
      conducted to assess its prevalence and clinical features in adult patients with
      lymphoma. METHODS: Retrospective analysis of 1352 patients with adult non
      Hodgkin's lymphoma showed 300 (22%) cases with gastrointestinal involvement at
      initial presentation. RESULTS: Of the 185 patients with primary gastrointestinal
      lymphoma, 94 (51%) had gastric primary lymphoma and the rest (49%) had a lymphoma
      of intestinal origin. Patients with intestinal lymphoma were considerably younger
      (median age, 35.0 years), frequently had multifocal disease (14%), and had a 10
      year survival rate of 48%. Cases with gastric primary lymphoma had a median age
      of 54.5 years (P < 0.001) and rarely had multifocal disease (1%; P < 0.001) but
      had an equal 10-year survival rate of 53% (P = 0.431). For both groups, the
      combined surgical resection followed by chemotherapy led to better 10-year
      survival (45%) compared with either modality used alone (0% and 35%,
      respectively; P < 0.05). Better survival was also noted in ambulatory patients,
      younger patients, those with localized disease, and those without intestinal
      perforation. Another 115 patients had gastrointestinal involvement secondary to
      disseminated disease with frequent high-grade histology (29%) and a poor 10-year
      survival rate of 22%. CONCLUSIONS: Gastrointestinal involvement is relatively
      common in patients with adult lymphoma. Multimodality treatment appeared superior
      to therapy with either surgery or chemotherapy used alone.

PMID- 8143992
TI  - Premicellar taurocholate enhances calcium uptake from all regions of rat small
      intestine.
AB  - BACKGROUND/AIMS: The specific components of bile, which is necessary for normal
      calcium absorption, are unknown. We have previously shown that Ca2+ is bound with
      high affinity by premicellar taurocholate. The current studies examined the
      effects of taurocholate on intestinal calcium transport. METHODS: Intestinal Ca2+
      uptakes were measured from proximal, mid, and distal small intestinal segments
      perfused with solutions containing 45CaCl2 (0.1-1 mmol/L), taurocholate (0-10
      mmol/L), trihydroxymethylaminomethane buffer (pH 7), phenolsulfonpthalein
      (nonabsorbable marker), and NaCl (total ionic strength, 0.16 mol/L) for four
      randomized perfusion periods. In other studies, the proximal small intestine was
      divided into two equal segments and perfused with either 45CaCl2 or 45CaCl2 plus
      taurocholate (2.5-5 mmol/L). Calcium absorption was measured from the difference
      in uptake and calcium concentration retained in mucosa. Finally, effects of
      taurocholate on Ca2+ uptake across isolated brush border membrane vesicles were
      measured. RESULTS: Premicellar taurocholate produced an approximately 1.7-2-fold
      enhancement (P < 0.01) in Ca2+ uptake in all regions, with lesser contributions
      from micellar taurocholate. These effects resulted in a net increase in calcium
      absorption. Premicellar taurocholate also significantly increased calcium uptake
      across brush border vesicles. CONCLUSIONS: Premicellar taurocholate significantly
      enhances calcium uptake into, and absorption across, enterocytes. The mechanisms
      remain to be experimentally verified.

PMID- 8143993
TI  - Failing deglutitive inhibition in primary esophageal motility disorders.
AB  - BACKGROUND/AIMS: Primary esophageal motility disorders (achalasia, diffuse
      esophageal spasm, and intermediate forms) are suggested to be caused by different
      degrees of inhibitory dysfunction; however, direct evidence for this hypothesis
      has never been presented in humans. The aim of this study was to measure the
      degree of inhibition that precedes deglutitive contractions in patients with
      primary motility disorders. METHODS: Deglutitive inhibition was examined in
      patients with primary motility disorders: 9 with achalasia, 6 with symptomatic
      diffuse esophageal spasm, and 5 with intermediate forms. An artificial high
      pressure zone was created in the esophageal body by inflating a balloon to a
      critical level, and pressure changes were measured at the interface between the
      balloon and esophageal wall. Inhibition was visualized as a relaxation of the
      artificial high-pressure zone. RESULTS: An inverse relationship was found between
      the degree of inhibition and the propagation velocity of the deglutitive
      contraction (r = 0.75; P < 0.001). Normally propagated contractions were preceded
      by an inhibition of 84.2% +/- 3.6%; fast-propagating contractions were preceded
      by partial inhibition of 40.6% +/- 6.2%; and, in case of simultaneous
      contractions, inhibition was absent, i.e., 2.6% +/- 1.6%. CONCLUSIONS: The
      spectrum of primary motility disorders is an expression of a progressively
      failing deglutitive inhibition.

PMID- 8143994
TI  - Biochemical epidemiology of colon cancer: effect of types of dietary fiber on
      colonic diacylglycerols in women.
AB  - BACKGROUND/AIMS: In view of the potential significance of dietary fat and fiber
      in colon cancer and the possible indirect involvement of diacylglycerols (DAGs)
      in the pathogenesis of colon cancer, the effect of types of dietary fiber on
      fecal DAG in premenopausal women was investigated. METHODS: Forty-eight women
      consuming a typical western diet provided two 24-hour stool specimens and two
      sets of preintervention 4-day food records. They were randomly assigned to one of
      the fiber groups, namely, a wheat, oat, or corn bran supplement. They consumed
      their control diet plus 13-15 g of dietary fiber from each source for 8 weeks. At
      the end of the fiber period, each subject provided two 24-hour stool specimens
      and 4-day food records. Stool samples collected during the two periods were
      analyzed for total fat and DAG fatty acids. RESULTS: All sources of dietary fiber
      increased the amount of fecal fat excreted. Dietary wheat bran decreased the
      concentrations of total DAG and DAG containing lauric acid, myristic acid,
      palmitic acid, stearic acid, and linoleic acid, whereas oat bran increased the
      DAG composed of oleic acid and linoleic acid compared with the control diet. Corn
      bran decreased the DAG containing stearic acid. CONCLUSIONS: These results show
      that the modifying effect of dietary fiber on DAG depends on the type of fiber
      consumed.

PMID- 8143995
TI  - Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer.
AB  - BACKGROUND/AIMS: Colon cancer is one of the major health problems in
      industrialized countries, and its incidence appears to be increasing. Surgical
      resectability is the most important prognostic determinant, although despite
      apparently curative surgery, recurrent tumors are common. Metastatic disease
      cannot be cured, and thus, there is a need for better adjuvant therapies.
      METHODS: Two hundred and thirty-nine patients with surgically resected colon
      cancer in Dukes' stage B2 or C were randomly assigned to chemotherapy or
      observation alone to determine whether adjuvant chemotherapy could effectively
      reduce the rate of cancer recurrence. One hundred and twenty-one patients in
      stage B2 and 118 patients in stage C were enrolled in the study. Adjuvant
      treatment consisted of folinic acid 200 mg/m2, intravenously, plus 5-fluorouracil
      400 mg/m2, intravenously, on days 1-5 every 4 weeks for 12 cycles. RESULTS: In
      stage B2, no significant difference between the adjuvant arm and the observation
      arm was noted. In stage C, adjuvant chemotherapy produced an advantage over
      observation in terms of a reduction in cancer recurrence rate with prolongation
      of a disease-free interval (P = 0.0016) and an improvement in overall survival (P
      = 0.0025). CONCLUSIONS: This study shows that folinic acid plus 5-fluorouracil
      adjuvant chemotherapy is effective in patients with surgically resected Dukes'
      stage C colon carcinoma.

PMID- 8143996
TI  - Determinants of response to a prokinetic agent in neuropathic chronic intestinal
      motility disorder.
AB  - BACKGROUND/AIMS: Reasons for the variable efficacy of prokinetic agents in the
      treatment of chronic intestinal motility disorders are unclear. The aim of this
      study was to assess the influence of extrinsic autonomic neuropathy and motility
      patterns on the symptom response to cisapride in 42 such patients. METHODS: A
      randomized, double-blind, placebo-controlled, two-dose (10 and 20 mg, three times
      daily), 12-week study included (1) measurement of autonomic (including abdominal
      vagal) function; (2) standardized 5-hour upper gastrointestinal manometry; and
      (3) assessment of symptoms based on visual analog scale at baseline and 6 and 12
      weeks. Statistical analysis compared symptom response among treatment and
      autonomic dysfunction groups and assessed the influence of absence of migrating
      motor complexes and presence of postprandial antral hypomotility on symptomatic
      responses to cisapride. RESULTS: There was no significant overall effect of
      cisapride in the entire group of 42 patients. Generalized sympathetic and vagal
      dysfunctions influence the response of patients with neuropathic chronic
      intestinal motility disorder to two doses of cisapride. CONCLUSIONS: Idiopathic
      intestinal motility disorder, unassociated with abdominal vagal dysfunction, is
      more likely to respond to cisapride. Detailed characterization of patient
      subgroups is crucial to designing treatment trials in patients with small bowel
      motility disorders.

PMID- 8143997
TI  - Small bowel motility following major intra-abdominal surgery: the effects of
      opiates and rectal cisapride.
AB  - BACKGROUND/AIMS: Human small bowel motility is altered after laparotomy. Opiate
      analgesia is a possible cause of these alterations, and cisapride is a potential
      therapy. METHODS: Continuous proximal small bowel manometry was performed for up
      to 92 hours in 23 patients after major intra-abdominal surgery. They were treated
      with rectal cisapride (30 mg three times daily) or placebo until the clinical
      resolution of ileus. Small bowel manometry was performed for 30 hours in 5
      volunteers receiving 1 mg/kg meperidine over 3 hours. RESULTS: Phase III activity
      was present within 3 hours of the end of surgery in all patients. Initially, the
      migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but
      gradually increased. Phase II activity was absent until a median of 40 hours had
      elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum,
      in contrast to that in the duodenum, presumably as a result of dilatation and/or
      altered tone, increasing to normal by 72 hours. In the volunteer group, although
      the MMC period was reduced by meperidine, it remained significantly greater than
      that of the placebo patient group for approximately 48 hours and phase II was
      reduced but not eliminated. Cisapride induced some changes in motor activity but
      did not accelerate the recovery of normal motility. Clinical outcome, assessed by
      the return of bowel sounds and passage of flatus, was accelerated by cisapride,
      but the trend was not significant (P = 0.11). CONCLUSIONS: This is the first
      published study using prolonged manometry to show the gradual evolution of small
      bowel motor activity after major intra-abdominal surgery. The findings suggest
      that surgery decreases the MMC period to the equivalent of the absolute
      refractory period, thereby eliminating phase II, which returns as the MMC period
      lengthens. Cisapride, at the dosage given, confers only modest benefit.

PMID- 8143998
TI  - Increased chemocytotoxicity to colon cancer cells by shock wave-induced
      cavitation.
AB  - BACKGROUND/AIMS: Cavitation has been shown to hinder colon cancer cell
      proliferation in vitro. This study aimed at investigating the interest of
      combining cavitation and cytotoxic drugs in vitro. METHODS: HT-29 cells were
      exposed in suspension to cavitation (shock waves plus bubbles) before 5
      fluorouracil (FUra) administration. Cytotoxicity was studied by means of
      clonogenic survival, cell proliferation by [3H]deoxyuridine ([3H]dUdR)
      incorporation, and influence of the treatments on the cell cycle by
      cytofluorimetry; the effects of cavitation on RNA incorporation of FUra, cell
      permeability, and activity of thymidilate synthetase (TS) were also studied.
      RESULTS: A preliminary exposure to cavitation (as compared with FUra alone)
      induced decreased colony formation (by up to 2 log in certain conditions) and
      colony size. Cavitation alone induced increased incorporation of [3H]dUdR during
      48 hours and stimulated TS activity, but in the presence of FUra, the
      concentration of the drug that causes 50% inhibition of control cell growth for
      [3H]dUdR incorporation was reduced by up to 1 log, and TS inhibition was
      increased after cavitation as compared with FUra alone. RNA incorporation of
      [14C]FUra was increased by cavitation, as a consequence of altered cell
      permeability rather than a direct RNA effect. Seventy-two hours after treatment,
      cavitation plus FUra decreased by more than 50% the S-phase fraction and also
      inhibited mitosis. CONCLUSIONS: Submitting HT-29 cells to cavitation before
      treatment by FUra significantly increases the effects of the drug. The action of
      both agents appears to be partially synergistic with a cycle specificity.

PMID- 8143999
TI  - Predominant symptoms in irritable bowel syndrome correlate with specific
      autonomic nervous system abnormalities.
AB  - BACKGROUND/AIMS: Irritable bowel syndrome may be influenced by the autonomic
      nervous system. Abnormalities in autonomic function, colon transit time, and
      psychological profiles in 21 patients were assessed. METHODS: Using modified
      Manning criteria for irritable bowel syndrome, patients were classified as
      constipation-predominant or diarrhea-predominant. Autonomic function was
      determined by one vagal cholinergic and two sympathetic adrenergic measures.
      Colon transit was assessed by radiopaque markers, and psychological profiles were
      determined by three inventories. RESULTS: Autonomic function tests showed that
      diarrhea-predominant subgroup values for one sympathetic adrenergic measure
      (postural adjustment ratio) were significantly different from controls (P <
      0.01). Constipation-predominant subgroup values were significantly lower for the
      vagal cholinergic measure R-R interval (P < 0.05). Colon transit measures
      differed by subgroup in left, right, rectosigmoid, and total colon transit times.
      Both subgroups differed significantly from controls on psychological measures;
      the constipation subgroup showed more psychological distress. CONCLUSIONS:
      Irritable bowel syndrome specific-symptom subgroups had different patterns of
      autonomic functioning, colonic transit, and psychological measures. The
      constipation subgroup is associated with a cholinergic abnormality and the
      diarrhea-predominant subgroup with an adrenergic abnormality. These findings
      suggest specific associations between the autonomic nervous system, predominant
      physical symptoms, colon transit time, and psychological factors in patients with
      irritable bowel syndrome.

PMID- 8144000
TI  - Intestinal vessels express a high density of somatostatin receptors in human
      inflammatory bowel disease.
AB  - BACKGROUND/AIMS: The neuropeptide somatostatin exerts multiple functions in the
      gastrointestinal tract and may also play a regulatory role in inflammatory bowel
      disease, as several other neuropeptides do, e.g., substance P or calcitonin gene
      related peptide. Therefore, the expression of somatostatin receptors was
      evaluated in tissue sections of diseased intestines and compared with controls.
      METHODS: Somatostatin receptors were measured in intestinal samples of 6 patients
      with Crohn's disease, 3 with ulcerative colitis, and 7 controls using
      somatostatin receptor autoradiography with 125I-[Tyr3]-octreotide or 125I-[Leu8,D
      Trp22,Tyr25]-somatostatin-28 as radioligands. Substance P receptors were measured
      similarly on adjacent sections. RESULTS: Somatostatin receptors are present in
      high density in most intramural veins, but not in arteries, of intestines in
      florid Crohn's disease or ulcerative colitis. The receptors are specific and of
      high affinity for somatostatin-14 and -28, as well as for octreotide.
      Somatostatin receptors remain undetectable in the veins of noninflamed control
      intestine. Substance P receptors are identified in the somatostatin receptor
      positive veins and also in arteries. CONCLUSIONS: The expression of receptors for
      somatostatin in veins of inflamed intestines suggests an active involvement of
      this peptide in the pathophysiology of inflammatory bowel disease and perhaps of
      inflammation in general.

PMID- 8144001
TI  - Tissue interleukin 1 and interleukin-1 receptor antagonist expression in
      enterocolitis in resistant and susceptible rats.
AB  - BACKGROUND/AIMS: Subserosal injection of purified group A streptococcal
      peptidoglycan-polysaccharide (PG-APS) induces chronic relapsing granulomatous
      enterocolitis and systemic inflammation in susceptible inbred Lewis rats but only
      transient intestinal injury in Buffalo and Fischer rats. Cecal interleukin 1 (IL
      1) and IL-1 receptor antagonist (IL-1ra) expression was measured in inbred rats
      displaying differential susceptibility to experimental enterocolitis. METHODS:
      The ileum and cecum of Lewis, Buffalo, and Fischer rats were subserosally
      injected with purified PG-APS or albumin. IL-1 and IL-1ra messenger RNA (mRNA)
      and protein (IL-1 only) were measured 1 or 27 days later. PG-APS-injected Lewis
      rats were treated with recombinant human IL-1ra. Kinetics of IL-1 and IL-1ra mRNA
      expression were studied in peritoneal cells. RESULTS: All rats strains developed
      acute inflammation with increased cecal concentrations of IL-1 beta and IL-1ra
      mRNA. Lewis rats developed chronic enterocolitis and had higher IL-1 and IL-1ra
      mRNA tissue levels than Buffalo or Fischer rats, which displayed no chronic
      inflammation. IL-1 beta and IL-1ra were produced by submucosal granulomas and
      correlated with inflammation. IL-1 alpha protein levels paralleled IL-1 beta mRNA
      expression. IL-1ra treatment attenuated acute and chronic enterocolitis,
      adhesions, and arthritis. PG-APS induced IL-1 and IL-1ra expression in peritoneal
      cells from Lewis and Fischer rats. CONCLUSIONS: Bacterial cell wall polymers
      stimulate IL-1 and IL-1ra expression in vivo and in vitro. These counterbalancing
      cytokines are increased in experimental enterocolitis and have important
      immunoregulatory roles in intestinal inflammation.

PMID- 8144002
TI  - Human esophageal secretion: mucosal response to luminal acid and pepsin.
AB  - BACKGROUND/AIMS: Although esophageal histology in humans reveals numerous
      submucosal mucous glands, their secretion has never been explored. Therefore, we
      have studied the chemical composition and physical characteristics of esophageal
      secretion under the impact of luminal saline, acid, and acid/pepsin solutions.
      METHODS: The esophageal lumen in 21 healthy volunteers was continuously perfused
      with saline, HCI, or HCI/pepsin. Perfusates were assayed for mucin, protein, and
      viscosity. In addition, analysis of amino acid and sugar composition of purified
      esophageal mucin was performed. RESULTS: Esophageal perfusion with saline
      resulted in luminal release of mucin at the rate of 0.23 +/- 0.03 mg.cm-2 x min
      1. Acid/pepsin solution significantly enhanced luminal release of mucin (0.32 +/-
      0.03 mg.cm-2 x min-1; P < 0.01). HCI/pepsin solution also significantly increased
      the luminal output of protein (P < 0.01) and significantly impaired the viscosity
      of the esophageal perfusate (P < 0.05). Threonine, serine, and proline were the
      major amino acids within the esophageal mucin, whereas galactose was the
      predominant carbohydrate. CONCLUSIONS: Luminally released esophageal mucin, shown
      for the first time in humans, contributes significantly to maintaining the high
      viscosity of esophageal secretions. Significant increase in the luminal release
      of mucin under the impact of acid and pepsin, with subsequent decline of the
      perfusate viscosity, may indicate that mucin is the major target for gastric acid
      and pepsin, absorbing the deleterious impact of the gastroesophageal refluxate.

PMID- 8144003
TI  - Circadian variations of epithelial cell proliferation in human rectal crypts.
AB  - BACKGROUND/AIMS: Evidence (almost exclusively from animal studies) suggests that
      proliferation within the colorectal mucosa undergoes circadian variations. The
      epithelial cells that line the human colorectal crypt occupy definite positions
      along the longitudinal axis according to their proliferative potential and degree
      of differentiation. Thus, circadian rhythmicity was investigated in humans to
      locate the areas along the longitudinal crypt axis in which diurnal fluctuation
      might occur. METHODS: Rectal mucosal biopsy specimens were obtained every 4 hours
      for a 24-hour span from each of 23 subjects (8 healthy volunteers and 15 with
      histories of sporadic adenomatous polyps). [3H]thymidine histoautoradiography was
      used to determine ratios of S-phase to total cells (total labeling index) in the
      crypt. Glands were also divided into 5 equal compartments from base (compartment
      1) to mouth (compartment 5), and labeling indices were calculated for each.
      RESULTS: Important temporal variations were confined to compartment 2 (F = 5.15,
      P = 0.0003) and total labeling indices (F = 3.57, P = 0.005). Despite individual
      variations, proliferation was generally higher at night and lower during
      afternoon. Upper-crypt proliferative rates (compartments 4 and 5) remained
      decidedly stable (F = 0.5, P = NS). Normal subjects and patients with polyps
      displayed similar circadian behaviors. CONCLUSIONS: Circadian fluctuation in
      proliferation is confined to the area of the crypt normally associated with
      replication. Upper-crypt indices, including those that were higher than normal (a
      colon-cancer risk marker) are stable over 24 hours. These findings should be
      useful in planning chemoprevention trials and chemotherapeutic regimens.

PMID- 8144004
TI  - Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats.
AB  - BACKGROUND/AIMS: Gastric microcirculatory disturbances are involved in the
      pathogenesis of stress ulcers; however, vasomodulators regulating this process
      are not fully understood. This study was conducted to investigate the role of
      endothelin 1 (ET-1) in hemorrhagic shock-induced gastric mucosal damage in rats.
      METHODS: ET-1 contents in plasma and gastric mucosa were measured and gastric
      mucosal damage was evaluated during a control period, 60 minutes of ischemia, 15
      minutes of reperfusion, and 30 minutes of postreperfusion. Next, effects of BQ
      123, an endothelinA receptor antagonist, on the gastric mucosal damage and
      hemodynamics were studied. RESULTS: Both plasma and mucosal ET-1 significantly
      increased after ischemia and reperfusion compared with the control values, but
      only mucosal ET-1 continued to increase after reperfusion, leading to the
      development of gastric mucosal damage. BQ-123, administered just before
      reperfusion, reduced mucosal damage in the postreperfusion period dose
      dependently and improved mean gastric mucosal blood flow and mucosal hemoglobin
      oxygen saturation during the 30-minute postreperfusion period. CONCLUSIONS: These
      results suggest that endogenous ET-1 plays an important role in the pathogenesis
      of hemorrhage shock-induced gastric mucosal damage through impairment of mucosal
      microcirculation. Further, endothelinA antagonists may have therapeutic benefits
      for shock-induced gastric mucosal damage.

PMID- 8144005
TI  - Quantitation of hepatitis C virus RNA in liver transplant recipients.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is common in liver transplant
      recipients, yet the effects of immunosuppression on HCV RNA levels and the
      relationship of HCV RNA levels to hepatic damage have not been studied. METHODS:
      To explore these issues, we measured HCV RNA in serum by polymerase chain
      reaction amplification and branched DNA assay from 100 HCV-infected patients
      undergoing liver transplantation. RESULTS: Mean posttransplant levels were 16
      fold higher than pretransplant values (7,935,000 and 496,000 Eq/mL, respectively;
      n = 65; P < 0.0001). Patients with high pretransplant levels had higher mean
      posttransplant levels than those with low pretransplant levels (17,119,000 and
      6,504,000 Eq/mL, respectively; P = 0.064). Posttransplant levels were similar in
      patients with recurrent and acquired infection and were independent of time of
      sampling. Fifty percent of patients with HCV infection had normal liver biopsy
      specimens, and there was no strong relationship between level of viremia and
      degree of hepatic damage. CONCLUSIONS: HCV RNA levels increase markedly following
      liver transplantation. The frequent finding of viremia in the absence of
      histological hepatitis suggests that a "carrier state" is common. Absence of
      allograft damage in some (despite high levels of viral RNA) suggests that in
      immunosuppressed patients, HCV infection may be tolerated without direct hepatic
      damage.

PMID- 8144006
TI  - [Clinical value of fractionation of peripheral erythrocyte pool in various anemic
      syndromes].
AB  - An original method is suggested for assessment of the profile of specific weight
      of peripheral blood red cell pool cells based on fractionation of washed red
      cells in verograffin discrete density gradients with due consideration for
      osmotic reactivity of verograffin solutions. Fifty-five donors and 90 patients
      with various anemic syndromes (iron-deficiency anemia, paroxysmal nocturnal
      hemoglobinuria, autoimmune hemolytic, B12-deficiency, and hypoplastic anemias,
      acute leukemia) were examined. Analysis of peripheral red cell pool helped
      specify the disease severity, monitor the adequacy of therapy, verify a
      remission, and predict the process recurrences. Moreover, study of red cell pool
      fraction composition permits assessment of the individual normal level of red
      cells and Hb in human blood, which is significant when making a person's "health
      passport".

PMID- 8144007
TI  - [Iron reserves in the female body and susceptibility to colds].
AB  - Levels of temporary invalidity because of catching cold were analyzed in 101
      working women over two years and these women's levels of serum iron, total iron
      binding capacity of the serum, transferrin saturation with iron, serum ferritin,
      and red cell ferritin measured. Women with stable iron reserves in the body
      virtually have no sick leaves because of catching cold, whereas in those with
      iron deficiency susceptibility to catching cold is increased, and if iron
      metabolism intensity in the body grows, invalidity periods are much longer.
      Normalization of not only iron reserves in the body, but correction of iron
      metabolism as well should be regarded as a factor exerting a favorable effect on
      body resistance to catching cold.

PMID- 8144008
TI  - [Disturbances of hemostasis and the genesis of hemorrhagic diathesis in patients
      with dysplastic scoliosis].
AB  - Dysplastic scoliosis often occurs with parallel hemostasis disorders and is
      fraught with the risk of intra- or postoperative risk of hemorrhagic
      complications. For early correction of hemostasis and adequate management of the
      patients, hemostasis parameters should be found out. Administration of indirect
      action anticoagulants is risky. The use of heparin or fraxiparin is more valid.
      The latter of them maintains the threat of postoperative hemorrhage onset in the
      least degree.

PMID- 8144009
TI  - [Tissue destruction as a mechanism initiating an external pathway of hemostasis].
AB  - Human and bovine brain tissues were used as a model to study phasic pattern and
      dynamic properties of lipid and protein components of damaged biological
      membranes as well as the relationships of this process with initiation of
      hemostasis external pathway. It was established that thromboplastic reaction is
      initiated by factor VII contact with the surface of apoprotein III-containing
      membrane. Enhanced mobility of borderline lipids correlated with thromboplastic
      activation of the membrane. The study made use of 1H, 31P-NMR and the test system
      specifically sensitive to apoprotein III.

PMID- 8144010
TI  - [Pathogenesis and therapy of joint inflammation in patients with hemophilia].
AB  - This study was aimed at investigation of immune status in patients with
      hemophilic arthropathies and design of optimal therapeutic programs for them. 103
      hemophiliacs were examined. Of them 56 patients had chronic productive synovitis
      and 47 osteoarthrosis. All the patients displayed higher levels of CIC and
      immunoglobulins than normal subjects, the highest values being registered in
      synovitis. Synovial fluid in them contained CIC and IgG, IgA, IgM. The findings
      suggest that immune disorders are actively involved in pathogenesis of hemophilic
      arthropathies. Programs of immunocorrecting therapy of synovitides and
      osteoarthroses including plasmapheresis and intraarticular administration of
      hormonal and cytostatic drugs produced a clinical response in 80% of the cases.
      The remission lasted up to 1 year.

PMID- 8144011
TI  - [Rheologic properties of the blood in infants with complicated pneumonia].
AB  - Blood rheology was assessed in 23 infants with acute pneumonia complicated with
      respiratory infectious toxicosis during hospitalization to intensive care wards,
      a control group consisted of 19 healthy infants. Plasma viscosity, red cell
      deformability, surface architectonics, and aggregation were studied. Patients
      developed increased plasma viscosity, marked reduction of red cell deformability,
      and increased aggregation index parallelled by reduced rate of aggregate
      formation. Changed red cell surface architectonics was associated with a reduced
      count of discocytes and parallel increase of echinocytes and cupola-like red cell
      forms. These data evidence marked disorders of blood rheology which should be not
      disregarded when choosing therapeutic policy.

PMID- 8144012
TI  - [Gas exchange and transport in the body during acute anemia correction by
      modified hemoglobin solution or attributed to inhalation of a hyperoxic gas
      mixture].
AB  - Total and specific characteristics of changes in gas exchange and transport,
      tissue oxygenation, circulatory and respiratory compensatory reactions were
      examined in three groups of necrotized Wistar rats during acute anemia correction
      by two methods, replacement of red cell mass loss with modified hemoglobin
      solution (Hb 4.4 g/dl, P50 21.5 mm Hg) or respiration with a hyperoxic mixture
      (90% of oxygen in nitrogen). In control animals anemia was induced with blood
      replacement with 6% albumin solution during atmospheric air inhalation. The
      studied methods for anemia correction were found to increase oxygen levels in
      arterial blood and similarly effective in total gas exchange maintenance; however
      the mechanisms of oxygen delivery from arterial blood to tissues being quite
      different, use of hemoglobin solution was associated with a number of adverse
      features in gas transport system, acid-base balance, reactions of minute volumes
      of circulation and respiration which were caused by changed oxygen-binding
      characteristics of modified hemoglobin and the presence of high concentrations of
      free hemoglobin in blood plasma.

PMID- 8144013
TI  - [Quantitative and functional characteristics of T-lymphocytes and monocytes in
      lymphosarcoma patients at various stages of the neoplastic process].
AB  - IKO monoclonal antibodies were used to study peripheral blood mononuclear types
      in 92 patients with various histomorphological types of diffuse lymphosarcoma at
      various stages of tumorous process. Absolute counts of CD7 and CD5 cells (T
      cells) were found reducing as was CD4 cell (T helpers) level as the disease
      progressed. CD8 cell (T suppressors) count reliably increased only in the phase
      of lymphoblastic lymphosarcoma leukemic degeneration. A group of patients with
      stage IV lymphoblastic lymphosarcoma was detected with drastically increased
      counts of mononuclears carrying mature T cell markers. Clinical course of the
      disease in these patients was characterized by the highest malignancy degree and
      metastatic involvement of the central nervous system. Examination of peripheral
      blood monocyte/macrophage ratio in the same patient population (n = 26) revealed
      reduced Fc receptor expression, EA phagocytosis, and increased levels of
      circulating immune complexes, these shifts augmenting with the tumor progress.
      The results may be valuable for prediction of lymphosarcoma course and for
      immunocorrection.

PMID- 8144014
TI  - [Interaction of human serum albumin with bilirubin in solution and in suspensions
      containing bile pigment of membranous particles].
AB  - Spectrophotometrically measured in homogeneous aqueous medium association
      constants for the formation of bilirubin--human human serum albumin complex did
      not correlate with the intensity of the same complex formation as a result of
      bilidiene release from nerve cell plasma membrane particles containing biliary
      pigment in aqueous medium during changed hydrogen parameter and ionic strength of
      the medium (pH22 degrees 6.8, 7.2, or 7.5 and NaCl concentration in the medium
      0.135, 0.150, or 0.165 M), such changes being compatible with normal mammalian
      cellular and tissue vital activity, the rest conditions being compatible. Study
      of the time course of the said complex formation in membranous particle
      suspension seems to be more adequate and therefore more reliable for organic
      anions (e.g. bilirubin) transport related assessment of detoxifying activity of
      infused human serum albumin preparations than measurement of the said association
      constants in a homogeneous aqueous medium.

PMID- 8144015
TI  - [Peripheral blood cells in clean-up workers of the Chernobyl nuclear power plant
      accident after a five-year follow-up].

PMID- 8144016
TI  - [Study of neutrophil function in clinical medicine. II. Adhesion, phagocytosis
      and bactericidal activity].

PMID- 8144017
TI  - [Pathogenetic mechanisms of efferent therapy (extracorporeal detoxification].

PMID- 8144018
TI  - [Rhesus system: in whom and how to determine Rhesus-identity?].

PMID- 8144019
TI  - [Change in iron metabolism as affected by ionizing radiation].
AB  - Iron metabolism parameters (increased level of serum ferritin, appearance of an
      iron pool specifically unrelated to transferrin, reduced ceruloplasmin level,
      etc.) were found changed in subjects who participated in liquidation of Chernobyl
      power plant accident aftereffects. These shifts in iron metabolism are explained
      by reduced antioxidant activity of plasma and indicative of mononuclear phagocyte
      dysfunction, thus necessitating a dynamic monitoring of this population.

PMID- 8144020
TI  - [Dynamics of iron metabolism in patients with homozygotic beta-thalassemia after
      splenectomy].
AB  - Iron metabolism was followed up in patients with homozygotic beta-thalassemia
      after 6 to 18 months, 2-3 years, and 4 to 12 years after splenectomy. Iron
      reserves of the body were found gradually increasing with time, this being
      expressed in very high values of serum and red cell ferritins and serum iron.
      Noteworthy is also an increase of circulating immune complex levels and
      appearance of a "free" pool of iron. This necessitates regular check-ups of iron
      metabolism parameters and timely correction of desferal dose.

PMID- 8144021
TI  - Mutational analysis of a baculovirus major late promoter.
AB  - We have used a linker-scan mutation strategy to analyze Pcap99, the proximal
      promoter of the Autographa californica nuclear polyhedrosis virus (AcMNPV) gene
      encoding the major capsid protein. A series of recombinant viruses expressing the
      cat reporter gene under the control of selected mutants of this promoter was
      constructed. Only mutations that altered bases within a region extending from 8
      bp upstream to 6 bp downstream from a TAAG sequence had a significant effect on
      expression from the late gene promoter. A synthetic promoter consisting of only
      these 18 bp (Pcapmin) was sufficient to direct late expression. Aside from this
      small region surrounding the TAAG, no evidence for distinct late activating or
      repressing sequence elements was obtained. Experiments comparing and combining
      late and very late gene promoter sequences suggest that late expression is
      intrinsically determined by the presence and immediate context of a TAAG sequence
      and that very late expression [as previously shown in Ooi et al., J. Mol. Biol.
      210 (1989) 721-736] results from additional modulation of TAAG-dependent
      expression by downstream promoter elements placed in an appropriate context. A
      compact combination promoter (95 bp), constructed by fusing Pcapmin to a linker
      modified very late polyhedrin promoter, directs strong expression at late and
      very late times post-infection.

PMID- 8144022
TI  - Cloning and characterization of a cDNA encoding elongation factor 1 alpha from
      chicken cells devoid of mitochondrial DNA.
AB  - Using a subtractive hybridization procedure, we isolated a cDNA clone encoding
      elongation factor 1 alpha (EF-1 alpha) from chicken cells devoid of mitochondrial
      (mt) DNA (rho0). The sequence encodes 1691 nucleotide (nt) residues and contains
      an open reading frame of 463 codons. Compared with the sequences from human,
      mouse and Xenopus laevis, the highest degree of sequence identity is detected in
      the 3' untranslated (> 90%) and coding (> 85%) regions. The gene evolved mainly
      by transitions occurring at the third codon position. Most transitions are silent
      and amino acid (aa) sequence identities are greater than 95%. Comparison of the
      protein domains interacting with cellular components (GTP/GDP, tRNAs and beta
      actin) reveals that they are highly conserved in species belonging to the four
      traditional eukaryotic kingdoms. The expression of the EF-1 alpha transcript is
      elevated in chicken rho0 cells. A single RNA band at 1800 nt is observed in both
      parental and rho0 cells. Southern blot analysis of restricted DNA from chick
      embryo fibroblasts (CEF) suggests that only one gene encoding EF-1 alpha exists
      in the chicken genome.

PMID- 8144023
TI  - Characterization of the chicken osteopontin-encoding gene.
AB  - A genomic clone of the chicken osteopontin-encoding gene (opn) was isolated and
      found to be organized as follows: an untranslated 5' exon; a signal peptide; a
      recognition sequence for phosphorylation by casein kinase II; a domain containing
      a possible O-linkage site for glycosylation; a second casein kinase II
      phosphorylation site; an exon containing three functional regions, the poly-Asp
      sequence of seven consecutive Asp residues, the RGD integrin recognition site and
      a potential N-linkage site for glycosylation; and a large C-terminal exon which
      also contains a potential N-linkage site for glycosylation. Primer extension
      analysis demonstrated only one strong transcriptional start point (tsp) in mRNAs
      prepared from embryonic bone and cultured osteoblasts. Analysis of the 5'
      flanking region identified a TATA sequence at -31, an inverted CAAT motif at -57,
      an AP1-recognition sequence at -84 and a putative vitamin-D-response element
      (VDRE) sequence at -474. Three plasmid constructs containing 963, 561 and 368 bp
      of 5' flanking sequence of the avian promoter were used to drive expression of
      bacterial cat. Comparison of the relative promoter activities of these constructs
      was carried out in MC3T3/E1 cells, a murine osteoblast cell line. All of the
      constructs showed approximately 20-fold the levels of expression over background
      activity of the cat gene without a promoter. Each construct also demonstrated a
      strong induction with phorbol-12-myristyl-13-acetate (PMA). In contrast,
      dihydroxycholecalciferol [1,25(OH)2D3] had neither a positive nor a negative
      effect on the 368- and 936-bp constructs, but was stimulatory for the 561-bp
      construct.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144024
TI  - Mouse erythroid cells express multiple putative RNA helicase genes exhibiting
      high sequence conservation from yeast to mammals.
AB  - RNA secondary structure is a critical determinant of RNA function in ribosome
      assembly, pre-mRNA splicing, mRNA translation and RNA stability. The 'DEAD/H'
      family of putative RNA helicases may help regulate these processes by utilizing
      intrinsic RNA-dependent ATPase activity to catalyze conformational changes in RNA
      secondary structure. To investigate the repertoire of DEAD/H box proteins
      expressed in mammals, we used PCR techniques to clone from mouse erythroleukemia
      (MEL) cells three new DEAD box cDNAs with high similarity to known yeast
      (Saccharomyces cerevisiae) genes. mDEAD2 and mDEAD3 (mouse DEAD box proteins) are
      > 95% identical to mouse PL10 but exhibit differential tissue-specific expression
      patterns; mDEAD2 and mDEAD3 are also approx. 70% identical (at the aa level) to
      yeast DED1 and DBP1 proteins. Members of this DEAD box subclass contain C
      terminal domains with high content of Arg, Ser, Gly and Phe, reminiscent of the
      RS domain in several Drosophila and mammalian splicing factors. mDEAD5 belongs to
      a second class related to translation initiation factors from yeast (TIF1/TIF2)
      and mammals (eIF-4A); this class contains a novel conserved peptide motif not
      found in other DEAD box proteins. Northern blotting shows that mDEAD5 is
      differentially expressed in testis vs. somatic tissues. Thus, mouse erythroid
      cells produce two highly conserved families of putative RNA helicases likely to
      play important roles in RNA metabolism and gene expression.

PMID- 8144025
TI  - Structural organisation of the rat genes encoding liver- and heart-type of
      cytochrome c oxidase subunit VIa and a pseudogene related to the COXVIa-L cDNA.
AB  - To study the tissue-specific expression of the heart(H)- and liver(L)-type of rat
      cytochrome-c oxidase subunit VIa (rCOXVIa), we have screened and sequenced the
      genes for the two isoforms. Both genes contain three exons and two introns,
      spanning 880 bp (rCOXVIa-H) and 3089 bp (rCOXVIa-L), respectively. In both genes,
      exon I codes for the whole leader sequence comprising 12 (rCOXVIa-H) or 26
      (rCOXVIa-L) amino acids and for 12 (rCOXVIa-H) or 10 (rCOXVIa-L) amino acids of
      the corresponding mature protein, while the remaining amino acids for the mature
      proteins are encoded by exons II and III. The 5' region of the genes lack both
      TATA and CAAT boxes, but show a high G+C content in the early 5'-upstream region.
      We have identified in upstream regions and in the introns of both genes several
      putative binding sites associated with respiratory function, muscle gene
      activation and housekeeping function. In rCOXVIa-H, we identified a CCAC/Myo-D
      motif, known to be required for muscle-specific expression of the human myoglobin
      encoding gene, which is not present in rCOXVIa-L. In addition, we have analyzed a
      pseudogene, showing 84% homology to the COXVIa-L cDNA sequence.

PMID- 8144026
TI  - An enhancer in the first intron of the human purine nucleoside phosphorylase
      encoding gene.
AB  - In previous studies characterizing intron-dependent expression of the human
      purine nucleoside phosphorylase-encoding gene (PNP), we identified a putative
      enhancer sequence in the first intron which was capable of mediating increased
      cat reporter gene expression in transfected murine NIH 3T3 cells in a position-
      and orientation-independent manner. In order to further characterize this
      enhancer activity, the nucleotide sequence was determined for the region of
      intron 1 to which this activity was originally ascribed. The sequence was
      analyzed for the presence of binding sites for known transcription factors, but
      none were identified. A 444-bp downstream portion of the intron-1 sequence
      enhanced cat expression either in conjunction with a human PNP promoter sequence
      or with a 105-bp heterologous herpes simplex virus thymidine kinase (TK)
      promoter. Nested deletions of the downstream intron-1 sequence fused to a TK::cat
      fusion gene localized the enhancer activity to a 170-bp sequence in intron 1. A
      154-bp HgiAI fragment (bp 424 to 577 of intron 1) excised from this region
      contained enhancer activity which varied directly with the number of fragments
      inserted upstream from the TK::cat fusion gene. However, inversion of the HgiAI
      fragment in a PNP abbreviated gene, or relocation of the HgiAI fragment from
      intron 1 to a position upstream from the PNP promoter, reduced or eliminated PNP
      expression. The effect of the intron-1 enhancer element on PNP expression is thus
      maximized in a position- and orientation-dependent manner.

PMID- 8144027
TI  - A negative cis-acting G-fer element participates in the regulation of expression
      of the human H-ferritin-encoding gene (FERH).
AB  - Ferritin (Fer) is the major iron storage protein in man. Its synthesis is
      regulated both at the translational and transcriptional levels. In previous
      studies on transcriptional regulation of the human H-ferritin-encoding gene
      (FERH), a 160-bp promoter segment was analyzed [Bevilacqua et al., Gene 111
      (1992) 255-260]. In order to obtain a more complete view of the elements involved
      in the transcriptional regulation of FERH, we have studied, in a further upstream
      region of the human FERH promoter (pFERH), a sequence between -272 and -291,
      named G-fer, because it contains a stretch of ten G, which binds a nuclear factor
      present in different cell types. DNA-binding assays and competition experiments
      suggest that the factor binding to G-fer has binding properties very similar to
      inhibitory factor-1 (IF-1), an ubiquitous factor that interacts with G-rich
      elements in the promoters of the mouse type-I collagen genes. DNA transfection
      experiments in HeLa cells, using either a wild-type or mutated pFERH fused to a
      reporter gene, showed that a 3-bp substitution mutation, that abolished the
      binding of the specific factor to G-fer, increased the promoter activity, thus
      suggesting an inhibitory role for the G-fer element and its cognate trans-acting
      factor.

PMID- 8144029
TI  - Sequence analysis and compositional properties of untranslated regions of human
      mRNAs.
AB  - A detailed computer analysis of the untranslated regions, 5'-UTR and 3'-UTR, of
      human mRNA sequences is reported. The compositional properties of these regions,
      compared with those of the corresponding coding regions, indicate that 5'-UTR and
      3'-UTR are less affected by the isochore compartmentalization than the
      corresponding third codon positions of mRNAs. The presence of higher functional
      constraints in 5'-UTR is also reported. Dinucleotide analysis shows a depletion
      of CpG and TpA in both sequences. A search for significant sequence motifs using
      the WORDUP algorithm reveals the patterns already known to have a functional role
      in the mRNA UTR, and several other motifs whose functional roles remain to be
      demonstrated. This type of analysis may be particularly useful for guiding site
      directed mutagenesis experiments. In addition, it can be used for assessing the
      nature of anonymous sequences now produced in large amounts in megabase
      sequencing projects.

PMID- 8144028
TI  - The human glucagon receptor encoding gene: structure, cDNA sequence and
      chromosomal localization.
AB  - Characterization of the human glucagon-receptor-encoding gene (GGR) should
      provide a greater understanding of blood glucose regulation and may reveal a
      genetic basis for the pathogenesis of diabetes. A cDNA encoding a complete
      functional human glucagon receptor (GGR) was isolated from a liver cDNA library
      by a combination of polymerase chain reaction and colony hybridization. The cDNA
      encodes a receptor protein with 80% identity to rat GGR that binds [125I]glucagon
      and transduces a signal leading to increases in the concentration of
      intracellular cyclic adenosine 3',5'-monophosphate. Southern blot analysis of
      human DNA reveals a hybridization pattern consistent with a single GGR locus. In
      situ hybridization to metaphase chromosome preparations maps the GGR locus to
      chromosome 17q25. Analysis of the genomic sequence shows that the coding region
      spans over 5.5 kb and is interrupted by 12 introns.

PMID- 8144030
TI  - Cloning and functional expression of a cDNA encoding coffee bean alpha
      galactosidase.
AB  - Purified coffee bean alpha-galactosidase (alpha Gal) has been used for removing
      terminal alpha-galactose residues from the glyco-conjugates at the red cell
      surface, in studies of blood group conversion. Here, we report the isolation and
      sequence of the full-length clone for coffee bean alpha Gal by using the
      polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE)
      techniques. The cDNA clone (1.4 kb) contains a single open reading frame which
      encodes a protein of 378 amino acids (aa). Its authenticity is confirmed by
      perfect alignment of aa sequences obtained from purified coffee bean alpha Gal,
      and by immune reaction with the antibody raised against the enzyme. Furthermore,
      the protein produced in insect cells shows enzymatic activity towards a synthetic
      alpha Gal substrate, p-nitro-phenyl-alpha-galactopyranoside.

PMID- 8144031
TI  - Pausing of simian virus 40 DNA replication fork movement in vivo by (dG-dA)n.(dT
      dC)n tracts.
AB  - We have earlier demonstrated that a sequence bordering an amplified DNA segment
      and containing the unusual sequence (dG-dA)n.(dT-dC)n could slow replication fork
      movement [Rao et al., Nucleic Acids Res. 16 (1988) 8077-8094]. This was done by
      cloning the unusual sequence in simian virus 40 (SV40) and following the rate of
      incorporation of radioactively labeled nucleotides into various regions of the
      SV40 genome. In the present study, we have analyzed the in vivo replicative
      intermediates of the SV40 variants containing the unusual sequences by a two
      dimensional gel electrophoretic technique. We found that the technique can be
      used to detect minor pauses in DNA replication and demonstrated that the cloned
      (dG-dA)n.(dT-dC)n tracts, that can potentially adopt triplex structures, could
      slow DNA replication fork movement. A sequence from the plasmid pUC18 did not
      slow fork movement when cloned in the same locus of SV40. The pause caused by the
      alternating guanosine-adenosine repeats might play a role in the regulation of
      DNA replication and gene amplification in vivo.

PMID- 8144032
TI  - Isolation and characterization of the Drosophila melanogaster eIF-2 alpha gene
      encoding the alpha subunit of translation initiation factor eIF-2.
AB  - Genomic and cDNA clones encoding the Drosophila melanogaster alpha-subunit of
      translational initiation factor 2 (eIF-2 alpha) were isolated. The D.
      melanogaster eIF-2 alpha gene encodes a 341 amino-acid (aa) protein that shares
      57 and 44% identity to its human and yeast homologues, respectively. The
      regulatory phosphorylation site at Ser50 is embedded in a segment of 19 conserved
      aa residues. Analysis of the genomic DNA and cDNA clones indicated that eIF-2
      alpha is a single-copy gene and its coding region is interrupted by a 260-bp
      intron. The D. melanogaster eIF-2 alpha mRNA is 1350 nt in length and is
      expressed throughout development.

PMID- 8144033
TI  - Polymorphic arylamine N-acetyltransferase encoding gene (NAT2) from homozygous
      rapid and slow acetylator congenic Syrian hamsters.
AB  - The nucleotide (nt) and deduced amino acid (aa) sequences were determined for
      polymorphic arylamine N-acetyl-transferase (NAT2) and its gene, NAT2, from
      homozygous rapid and slow acetylator congenic Syrian hamsters. The slow
      acetylator (NAT2s) allele contained three point mutations which differed from the
      rapid acetylator allele (NAT2r); two mutations were silent, and the third
      mutation resulted in a premature stop codon. The NAT2s allele contained a
      truncated open reading frame of 726 nt encoding a 242-aa protein, which is 48-aa
      shorter than NAT2r.

PMID- 8144034
TI  - Nucleotide sequence of the bovine vimentin-encoding cDNA.
AB  - Using reverse transcription-polymerase chain reaction (RT-PCR), we have amplified
      vimentin (Vim)-encoding sequences from both total and polyadenylated bovine lens
      RNA. The amplified products were cloned and the nucleotide sequences determined.
      The amino-acid sequence of bovine vimentin shows 97.2, 96.8, 96.3 and 84.9%
      homology with reported aa sequences of human, mouse, hamster and chicken Vim,
      respectively.

PMID- 8144035
TI  - The porcine thromboxane synthase-encoding cDNA: sequence, mRNA expression and
      enzyme production in Sf9 insect cells.
AB  - A full-length cDNA encoding porcine thromboxane synthase (TS) was isolated and
      sequenced. The open reading frame encodes a 534-amino acid (aa) protein (M(r)
      60,451) which shares more than 75% identity with TS from other species and is 30%
      homologous to several enzymes of the cytochrome P-450 III family. Sequence
      comparison among porcine (p), human (h), and murine (m) TS indicated conservation
      of eight Cys residues and one putative N-glycosylation site. Several highly
      conserved regions were identified at the near N terminus, middle and C terminus.
      The most divergent region lies at aa residues 290-325, within which a Lys308
      residue was unique to pTS. Between aa residues 70 and 90, considerable divergence
      was observed in mTS. Northern analysis showed that the pTS gene was expressed as
      a 2.3-kb transcript primarily in lung, kidney and thymus. A high-titer
      recombinant (re-) baculovirus containing pTS cDNA was developed to conduct a time
      course study of enzyme production in Spodoptera frugiperda (Sf9) cells. TS
      activity was detectable in the microsomes of Sf9 cells 12-h post-infection and
      reached maximum by 48 h. The produced TS resembles purified pTS in catalysis, as
      well as inhibition by a substrate analog inhibitor.

PMID- 8144036
TI  - Human monocyte chemoattractant protein-1 expressed in a baculovirus system.
AB  - Human monocyte chemoattractant protein-1 (hMCP-1) was produced using a
      baculovirus system. The hMCP-1 cDNA was inserted into the genomic DNA of
      Autographa californica nuclear polyhedrosis virus (AcNPV) using a transfer
      vector, pJVP10Z. Spodoptera frugiperda insect cells, which were infected with
      this recombinant virus, secreted recombinant hMCP-1 (re-hMCP-1) at the level of
      10-20 micrograms/ml of culture medium. This product was shown to chemoattract
      monocytes. Three distinct bands of 11, 11.5 and 12 kDa were revealed by
      immunoblotting analysis, and this heterogeneity was assigned to differences in
      carbohydrate processing. N-terminal amino-acid sequence analysis of the purified
      product revealed identity with hMCP-1. Thus, in this system, re-hMCP-1 was
      produced in large quantities and modified in a manner similar to native hMCP-1.

PMID- 8144037
TI  - Genomic cloning of human thioredoxin-encoding gene: mapping of the transcription
      start point and analysis of the promoter.
AB  - Thioredoxin (TR) is a small ubiquitous dithiol-reductase enzyme first identified
      in bacteria and plants. In recent years, this protein has been recognized as
      playing an important role in the growth control of eukaryotic cells, especially
      in lymphocytes. It was first cloned from a human Epstein-Barr virus-transformed
      lymphoblastoid B-cell line by our group in 1988 [Wollman et al., J. Biol. Chem.
      263 (1988) 15506-15512] and localized on chromosome 3 p11-p12 by in situ
      hybridization [Lafage-Pochitaloff-Huvale et al., FEBS Lett. 255 (1989) 89-91].
      The present work was performed to study the genomic organization of the human
      thioredoxin (hTR)-encoding gene (hTR). The screening of a human genomic library
      in lambda EMBL4 phage led to the identification of two genomic clones which
      encompassed the entire gene, including the promoter region. The coding region of
      hTR spans over 13 kb and is organized into five exons separated by four introns
      which were 60% sequenced. We determined the transcription start point (tsp) by
      primer extension. This tsp located, in lymphocytes, 22-bp downstream from a TATA
      box (TATAA) defines a 5' untranslated region of 74 bp. We analyzed 2149-bp
      upstream from the promoter for sequence motifs which could bind regulatory
      proteins. This promoter contains many possible regulatory elements compatible
      with both a basal constitutive expression and a regulated inducible
      transcription, especially by cytokines such as interleukin-6 and interferons.
      Finally, Southern hybridization of genomic DNAs from several donors detected only
      one active gene encoding hTR.

PMID- 8144038
TI  - The thiol-specific antioxidant protein from human brain: gene cloning and
      analysis of conserved cysteine regions.
AB  - The complete cDNA encoding human thiol-specific antioxidant protein (PRP) was
      isolated from a human brain cDNA library in the lambda Zap expression vector. An
      open reading frame (ORF) was identified and found to encode a polypeptide of 197
      aa with a M(r) of 21,729. The cDNA contained 98 bp of 5'-untranslated sequence
      (UTR) and 259 bp of 3'-UTR containing a poly(A) signal, AATAAA. Expression of the
      human PRP cDNA in Escherichia coli yielded a functionally active protein. The
      observed local sequence homologies between human PRP and other homologous
      proteins whose functions have not yet been defined give important insight into
      elucidating the biochemical function of a new protein family which has highly
      conserved regions containing cysteine.

PMID- 8144039
TI  - Repetitive DNA in and around translocation breakpoints of the Philadelphia
      chromosome.
AB  - This paper describes systematic sequence studies of repetitive DNA in and around
      translocation breakpoints on chromosomes 9 and 22, which are involved in the
      formation of the Philadelphia chromosome in acute leukemias. In addition to Alu
      repeats described in previous studies, the breakpoint regions appear to contain
      many other repetitive elements, including a member of a new repetitive family
      (MER34) reported in this paper. Identification of these repeats broadens current
      studies on the possible involvement of repetitive DNA in this intensely studied
      chromosomal translocation.

PMID- 8144040
TI  - The murine glutamine:fructose-6-phosphate amidotransferase-encoding cDNA
      sequence.
AB  - Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the rate-limiting
      enzyme in hexosamine synthesis and has been implicated in the control of growth
      factor gene expression. We cloned a mouse cDNA which is 91% homologous to the
      human sequence. The deduced amino-acid sequence shows 98.6% identity to human
      GFAT. The cDNA is derived from a 7-kb mRNA in the mouse, while there are multiple
      sized human mRNAs.

PMID- 8144041
TI  - Cloning and sequencing of a cDNA encoding the rat Bcl-2 protein.
AB  - A rat cDNA encoding the Bcl-2 protein was cloned and sequenced. The primary amino
      acid sequence deduced from the nucleotide sequence reveals a 236-aa protein
      having extensive homology with the mouse (95%), human (87%) and chicken (71%) Bcl
      2 proteins.

PMID- 8144042
TI  - A human cDNA sequence homologue of bovine phosphatidylethanolamine-binding
      protein.
AB  - Sequencing of about 1000 3'-directed cDNA clones from the human HepG2 cell line
      revealed that about half of them represent transcripts of abundantly or
      moderately expressed genes, about 70% of which are novel. We identified one of
      these clones as encoding the human homologue of bovine phosphatidylethanolamine
      binding protein.

PMID- 8144043
TI  - Identification of an active gene by using large-scale cDNA sequencing.
AB  - A 3'-directed partial cDNA clone that matches exactly a genomic sequence in
      GenBank was isolated while collecting transcribed sequences from adult lung by a
      random approach. This is the first report of active gene identification on
      genomic sequence without the aid of Northern hybridization.

PMID- 8144044
TI  - Cerebral metabolic responses to meta-chlorophenylpiperazine are reduced during
      its chronic administration to young and aged rats.
AB  - The effects of the 5-HT agonist meta-chlorophenylpiperazine (MCPP) on regional
      cerebral metabolic rates for glucose (rCMRglc) were measured in 3- and 24-month
      old rats that were not pretreated or were pretreated for 2 weeks with continuous
      infusion of saline or MCPP. rCMRglc were measured using the quantitative
      autoradiographic [14C]2-deoxy-D-glucose technique in 71 brain regions at 15 min
      after acute administration of MCPP 2.5 mg/kg. In the absence of chronic
      pretreatment, intraperitoneal MCPP 2.5 mg/kg produced widespread rCMRglc
      reductions (41 brain areas) in 3-month-old rats and more limited rCMRglc
      decreases (8 brain areas) in 24-month-old rats. After chronic treatment, MCPP
      failed to reduce rCMRglc in any region of either group of rats. These findings
      indicate that mechanisms of downregulation of response to MCPP are functional in
      young and aged rats and suggest that the age-related reduction in rCMRglc
      responses to acute MCPP in non-pretreated animals may be due to compensation for
      age-related losses of 5-HT terminals.

PMID- 8144045
TI  - Effects of a whole-body resistive training regimen in the elderly.
AB  - Twenty active elderly subjects (mean age = 66.4 years, range 51-81) participated
      in a 12-week weight-training program to determine the possibility of increasing
      muscular strength and lean body weight. The training utilized variable resistance
      weight machines which trained the major muscle groups. The male subjects (n = 11)
      experienced an average increase of 66.1% (SD = 19.39, p < 0.00001) in total
      maximum weight lifted while the females (n = 9) showed an average increase of
      72.2% (SD = 33.44, p < 0.001). Lean body weight, which was calculated by skinfold
      measurements for each group did increase, but was not statistically significant
      (males p < 0.11, females p < 0.18). The study demonstrated the positive effects a
      weight-training regimen can have on an elderly population.

PMID- 8144046
TI  - Effects of age and gender on functional rotation and lateral movements of the
      neck and back.
AB  - Using two-dimensional video analysis, the effects of age and gender on functional
      rotation and lateral flexion of the back and neck were examined in 110 subjects.
      Equal numbers of male and female subjects were blocked into five age groups for a
      lifespan analysis: 6-8, 12-15, 20-30, 40-50, 60-80 years. Each subject performed
      three movements: a neck rotation, neck and back rotation, and a neck and back
      lateral flexion. The degree of movement was determined by the Peak Two
      Dimensional Motion Measurement Analysis System. No significant gender difference
      was found for any of the movements tested though spinal mobility decreased
      significantly with age and became more variable. The oldest age group was
      significantly less flexible than all younger age groups on all three movements.
      Significant differences were also found between the youngest age group and the
      middle adults on all movements.

PMID- 8144047
TI  - Delayed recovery of lymphocyte beta-adrenoceptors in thyroidectomized aging
      patients.
AB  - We previously found that the beta-adrenoceptor (beta AR) density of lymphocytes
      from thyroidectomized adult women shows a significant decrease early after
      surgery, followed by a slower recovery kinetics. In the present article, we posed
      the question whether the kinetics of lymphocyte beta ARs from thyroidectomized
      patients could be dependent upon the age of the donors. Thus, postsurgical
      decrease and the following recovery of beta AR density were studied in
      thyroidectomized female patients of different ages, along with the time course of
      triiodothyronine (T3) and thyroxine (T4) levels. The kinetics were analyzed using
      a mathematical model fitting experimental data. Results show that parallel
      statistically significant falls in beta AR density and T3 levels are present in
      every age group tested from 1 to 3 days following surgical intervention. No
      statistically significant changes have been observed in T4 levels. The recovery
      of beta AR density shows progressively slower kinetics with increasing patient
      age. In particular, a parameter estimating the time required to regain 50% of the
      fall in beta AR density increases exponentially with advancing age. T3 levels
      show a recovery trend quite similar to that of beta AR density, but the kinetics
      is slower and does not present any statistically significant age-related changes.
      The kinetics of T4 levels are completely different, showing a continuous slowly
      decreasing trend. Thus, the beta AR fall can be accounted for only by a decrease
      in T3 levels. On the contrary, the comparison of T3 and beta AR kinetics suggests
      that receptor recovery is also mediated by other regulatory factors. T4 levels do
      not appear to have any direct role in both fall and recovery of beta ARs.

PMID- 8144048
TI  - Association between high concentration of antibodies to insulin and some diseases
      common in the elderly.
AB  - Antibodies to insulin (IA) were measured by graded hemagglutination in 164
      patients and in 90 control subjects aged 18-65 years. The greatest prevalence of
      these antibodies was found in patients with the organic mental syndrome, of whom
      70% (n = 110) had an antibody concentration above the normal 95th percentile.
      Among patients with diabetes, hypertension and cerebrovascular accidents, 42% had
      a high concentration of IA, while in all other geriatric patients (n = 21) the
      concentration of these antibodies was within the normal range.

PMID- 8144049
TI  - Spontaneous bile reflux in the elderly.
AB  - Duodenogastric bile reflux is common in postoperative stomach but has been
      reported in intact stomachs. Spontaneous bile reflux in the elderly has not been
      studied before. This has been assessed in dyspeptic elderly and young patients.
      Total bile acid (TBA) levels and pH were measured in the samples of fasting
      gastric juice. Antral biopsies were taken for histological examination including
      Helicobacter pylori identification. TBA levels were significantly higher in
      elderly patients with gastritis in comparison to elderly and young normal groups.
      Only 10% of elderly patients with gastritis and 7% with gastric ulcer has
      abnormal TBA (> 1 mmol/l). There was some correlation between the pH and TBA but
      a significant proportion of elderly patients has pH > 4 with a normal TBA. TBA
      levels were not significantly different in H. pylori +ve and H. pylori -ve
      patients. Nineteen elderly patients had evidence of reactive gastritis. Five of
      these patients had raised TBA levels with severe H. pylori infection. The
      remaining 15 patients had normal TBA. These patients were on NSAIDs and 4 of them
      had H. pylori infection. We conclude that spontaneous bile reflux in the elderly
      is uncommon. Hypochlorhydria which is observed in the elderly is not caused by
      alkaline bile reflux. The main cause of reactive gastritis in the elderly is
      NSAIDs ingestion.

PMID- 8144050
TI  - The role of anthropometry in the assessment of malnutrition in the hospitalized
      frail elderly.
AB  - Although common among the hospitalized frail elderly, malnutrition is often
      unrecognized by clinicians, and its identification is fought with difficulty due
      to inadequate nutritional assessment methods and standards. This study compared
      the use of percent ideal body weight (%IBW) and anthropometry in the assessment
      of malnutrition in the hospitalized frail elderly. Approximaty 45% of patients
      studied had at least two anthropometric measurements below the 5th percentile, a
      level reflecting severe malnutrition. However, only 28% of patients were found to
      be less than 90% IBW, a level reflecting only mild to severe changes in body
      weight. Serum albumin was below normal (< 35 g/l) in 30% of patients. The total
      lymphocyte count was below normal (< 1,500 cells/mm3) in 53%, and was severely
      depressed (< 800 cells/mm3) in 24%. Thus, despite the use of stringent
      anthropometric criteria indicating severe malnutrition, anthropometry appeared
      more sensitive than %IBW as a measure of malnutrition in the hospitalized frail
      elderly. Furthermore, acute illness causes changes in commonly employed blood
      measures which make them unreliable in the assessment of malnutrition in this
      population. Anthropometry may prove to be the most stable, easily performed, and
      sensitive measure of malnutrition in the hospitalized frail elderly. However,
      further studies are clearly needed, including the development of appropriate
      anthropometric reference standards for the very old, a population that commonly
      suffers malnutrition.

PMID- 8144051
TI  - [Effect of aminophylline on frequency of blood flow in utero-placental and fetal
      circulation, on arterial blood pressure and on cardiotocography].
AB  - Aminophylline was given (125 mg i.v.) in 24 cases with fetal hypotrophy. Blood
      flow was measured (Doppler technique) before aminophylline injection, 30 min. and
      3-4 hours after. Blood pressure was monitored continuously, CTG was performed
      many times before and after administration of aminophylline. After administration
      of aminophylline diastolic blood pressure decreased during 3-4 hours and blood
      flow in the arcuate artery increased. There were no changes in the blood flow in
      the umbilical artery and fetal aorta after administration of aminophylline. We
      didn't observe any changes in CTG before and after administration of
      aminophylline.

PMID- 8144052
TI  - [Urinary tract infections in newborns].
AB  - The retrospective analysis had been performed on 3480 newborns weighted more than
      1001 g, over the period of thirty one months. There was evaluated the frequency
      (1.25%), and clinical manifestation of the disease in newborns. Male and full
      term infants suffered from the disease more frequently then other evaluated
      infants. About half of cases were asymptomatic in the beginning of disease, and
      in the majority part of them, course of illness were non-characteristic. There
      was observed generalised oedema and swellings, irritability, intensive jaundice,
      dehydration, fever and poor peripheral perfusion. Laboratory findings manifested:
      anemia, hypoglycemia, higher WBC, metabolic acidosis, and especially
      hyperbilirubinemia, and in urine: pyuria and proteinuria mainly. In most cases of
      the disease urea and creatinine level in the serum were normal. The most dominant
      pathogenic agent was E. coli (above 72%).

PMID- 8144053
TI  - [Usefulness of transvaginal ultrasound and hysteroscopy in diagnosing endometrial
      hyperplasia and endometrial carcinoma].
AB  - Modern methods enabling evaluation of endometrium in all phases of the menstrual
      cycle were presented. Transvaginal ultrasound does not give characteristic
      pictures. The most frequently observed sonographic features in endometrial
      hyperplasia and endometrial carcinoma were compared. Most frequently, in 29% we
      observed the thickening of the endometrium. The enlargement of the uterine body
      was detected in 27%. The dominant feature in endometrial carcinoma was distortion
      or lack of medium-focus echo-90%. Different echogenicity was observed in 69% of
      all cases. Application of hysteroscopy enables us to visualize changed
      endometrium and also to sample focal lesions for histopathological examination.
      Endometrial carcinoma was detected in all analyzed cases with application of
      hysteroscopy and ultrasound. Pathological endometrial hyperplasia was diagnosed
      by ultrasound only in 44% and with application of hysteroscopy in 84% of all
      material.

PMID- 8144054
TI  - [Side effects of drug treatment for ovarian cancer after administration of
      antiemetic drugs].
AB  - The occurring frequency of 14 most common chemotherapy and anti-nausea drug side
      effects was examined. The studies were performed on 29 women with ovarian cancer
      treated by total number of 125 chemotherapy courses (schedule PAC and Acy) and
      additionally, in order to eliminate nausea caused by the chemotherapy, by anti
      nausea drugs (Zofran, Solu-Medrol, Droperidol, Metoclopramide + Fenactil,
      Torecan). Zofran caused the fewest number of side-effects, solu-medrol inhibited
      nausea and vomiting significantly, however it caused many side-effects such as
      flush on a face, restlessness, incitement and headaches. Torecan did not prevent
      patients from vomiting. The greatest number of side-effects was observed after
      droperidol and metoclopramide + fenactil treatment.

PMID- 8144055
TI  - [Formation of an artificial vagina using Vecchietti's method].
AB  - In our report we present the use of the Vecchietti method in our modification to
      form an artificial vagina in women with Rokitansky-Kuster-Hauser syndrome. Five
      surgical procedures were carried out and expected therapeutic result was obtained
      in the all cases. This method was estimated as very safe. No side effects were
      observed.

PMID- 8144056
TI  - [Uterine endoscopy. I. Role of hysteroscopy in gynecologic oncology].
AB  - The historical sketch of development of hysteroscopy is presented. At the present
      time instrumentation consists of the set of precision lenses system, with "cold
      light" source and the light conveying glass fibre. In order to obtain good
      visibility and ability to perform surgeries one uses various media for distention
      of the uterine walls. For diagnostic hysteroscopy the most commonly used medium
      is carbon dioxide. The most advantageous substances when performing intrauterine
      procedures are liquid media such as: HYSKON, MANNITOL and GLUCOSE SOLUTION.
      Indications for hysteroscopy are numerous and they divide into diagnostic and
      surgical. Hysteroscopy is a very useful procedure in diagnosis and therapy of
      sterility and diagnosis and therapy of hyperplastic changes of the endometrium.
      Introduction of resection of the endometrium to hysteroscopy allows us, in
      certain situations to limit the number of laparatomies. Complications after
      hysteroscopy do not differ from complications following other gynecological
      surgeries.

PMID- 8144057
TI  - [Ectopic pregnancy in the stump of the uterine tube after in vitro
      fertilization].
AB  - A rare case of ectopic pregnancy in stump of uterine tube after IVF, which was
      done after bilateral removal of uterine tubes, caused by uterine tube pregnancies
      was described. Diagnostic difficulties were shown in that case.

PMID- 8144058
TI  - [Prophylactic and theoretic psycho-medicine during 40 years of university
      activity].

PMID- 8144059
TI  - The regulation of hypothalamic CRH: impact of in vitro studies on the central
      control of the stress response.

PMID- 8144060
TI  - Auditory and visual event-related potentials in patients suffering from
      Alzheimer's dementia and multiinfarct dementia, before and after treatment with
      piracetam.
AB  - We have done a study on 7 subjects suffering from Alzheimer's dementia (AD) and
      15 subjects suffering from multiinfarct dementia (MID) to see whether they
      manifest any changes of amplitudes or latencies concerning event-related
      potentials (ERP) compared to a group of normal controls and how three months of
      treatment with piracetam affects those changes. We found that the latencies of
      all waves are longer in the groups of subjects suffering from AD and MID compared
      to the normal controls, except for the N100 wave, which showed shorter latency in
      the AD group. Amplitudes were lower in the groups of patients suffering from AD
      and MID. These changes were most prominent for the P300 wave. Treatment with
      piracetam reduced those changes in the precognitive part, though it seemed to
      have no effect on the cognitive part.

PMID- 8144061
TI  - A new look at sleep position via head slant.
AB  - We investigated whether the degree of plagiocephaly (P) (head slant) would
      predict the particular "position of comfort" adopted prior to sleep. A marked
      flattening of the right occipital bone (left-dominant occipital plagiocephaly)
      was noted for the majority of our subjects, coupled with a tendency to prefer a
      right-sided "position of comfort". Two subjects exhibiting right-dominant
      occipital P adopted an extreme left-sided sleep position, providing further
      support for this relationship. We call attention to the possibility that the
      "position of comfort" adopted prior to sleep, may be a variable of relevance for
      the entire sleep cycle.

PMID- 8144062
TI  - Transient ischemic attacks associated with amfepramone therapy: a case report.
AB  - A 33-year-old man was prescribed amfepramone 75 mg o.i.d. for the treatment of
      obesity. One week after onset of therapy, he suddenly became agitated and aphasic
      for several h. A CT scan of the brain was normal. Amfepramone was discontinued.
      Three days later, there was a second period of agitation and aphasia with a
      discrete right hemiparesis lasting 12 h. A repeat CT scan and a MRI of the brain
      were normal. On EEG and brain mapping, alpha-activity was absent over the left
      hemisphere and a left fronto-temporal delta-focus was found. A Tc-99m HMPAO brain
      SPECT showed a severe hypoperfusion of the left hemisphere. The next day, the
      neurological examination was completely normal. Two weeks later, EEG and SPECT
      had completely normalized. Transient ischemic attacks due to vasospasm were
      considered to be the most probable clinical diagnosis.

PMID- 8144063
TI  - Lactobacillus casei endocarditis in an intravenous heroin drug addict: a case
      report.
AB  - A 24-year-old HIV negative unemployed intravenous heroin addict with teeth in
      poor condition was admitted to hospital with left hemiparesis; CT scan of the
      brain revealed a hypodense area in the right parietal region. He was apyrexial
      with marked leukocytosis and raised ESR, had an aortic diastolic murmur and an
      echocardiogram showed marked aortic insufficiency with possible small vegetations
      on the anterior leaflet of the mitral valve. Lactobacillus Casei was isolated
      from repeated blood cultures. Therapy with penicillin G together with netilmicin
      for 6 weeks led to improvement of his clinical status and an echocardiogram on
      discharge showed clear improvement. Regression of the cerebral lesions was also
      demonstrated on CT scan. We conclude that lactobacillus species should be sought
      in all haemoculture negative endocarditis in the presence of tooth disease.

PMID- 8144064
TI  - Short temperament questionnaire for children aged 8-12 years in the city of Rome.
AB  - The assessment of temperament is usually measured by means of parental
      questionnaires. Since temperament questionnaires in children aged 8-12 years do
      not exist in Italy we planned a study to develop an Italian questionnaire.
      Initially we tried to adapt Hegvik et al.'s questionnaire and delivered 389
      questionnaires to the mothers of children aged 8-12 years, but most of them were
      given back uncompleted, essentially because they often described behavior not
      usually observed in Italian children. Then we prepared a new, short (30 items)
      questionnaire which we distributed to 431 mothers of children aged 8-12 years.
      This new questionnaire was completed by 98.76% of mothers and a high three week
      rating-re-rating reliability for the different temperamental characteristics
      under assessment was proved. We believe that this new questionnaire is reliable
      for temperament assessment in Italian children aged 8 to 12 years, living in a
      big city environment in Central Italy.

PMID- 8144065
TI  - Re: Thallium-201 spect in cerebral lymphoma.

PMID- 8144066
TI  - [Intraosseous ganglion of the scaphoid bone--a case report].
AB  - This is a case report of a 21-year-old male who suffered from wrist pain. X-rays
      showed a bone cyst of the scaphoid. Intraoperatively, an intraosseous ganglion of
      the scaphoid with articular communication was found. Symptoms and clinical
      characteristics of the intraosseous ganglion are discussed and recent literature
      reviewed.

PMID- 8144067
TI  - [Retinaculum-plasty in dorsal wrist ganglion].
AB  - Pathogenesis and clinical manifestations are described. Ganglion extirpation
      often leaves larger defects in the joint capsule of the wrist, causing problems.
      A flap using parts of the retinaculum extensorum provides a reliable closure of
      the joint capsule defect and may reduce the risk of ganglion recurrences.

PMID- 8144068
TI  - [Closure of rheumatic palmar perforations of the wrist capsule with a flap of
      retinaculum flexorum].
AB  - In 53 hands with rheumatoid arthritis, bony spurs of the scaphoid and trapezium
      were found perforating the capsule of the radial wall of the carpal tunnel. After
      removal of the spurs, the remaining capsular defect was covered by a flap of the
      flexor retinaculum. The flap is raised from the flexor retinaculum in a width of
      approximately 15 mm by parallel transverse incisions and is based radially. Then
      it is brought down to the defect and sutured to the local ligaments. The blood
      supply of the retinacular flap is well preserved. The flap provides a reliable
      cover of the capsular defect as well as a smooth gliding surface for the flexor
      tendons.

PMID- 8144069
TI  - [Synovial flap repair in treating recurrent carpal tunnel syndrome].
AB  - In 1980, we presented the synovialis flap plasty for the treatment of carpal
      tunnel syndrome recurrence. Since May 1979, we performed 41 secondary procedures,
      and among them 14 synovialis flap plasties. The results were very good in three
      patients, good in eight, satisfactory in two, and poor in one, but this patient
      with the poor result reported subjective improvement.

PMID- 8144070
TI  - [Experience with stemless proplast as trapezium prosthesis].
AB  - From 1985 to 1991, we performed 58 trapezium implantations using porous proplast
      surrounded by a silastic cylinder. This stemless proplast prevents
      proximalisation of the thumb as well as the diminution of strength after removal
      of the trapezium. Contrary to the Swanson-implants, we did not find a radio
      dorsal dislocation in our patients. The operative technique is very simple. With
      the tissue growing into the proplast, a secondary dislocation, especially while
      loading, is avoided. So far, all patients are satisfied with the result of the
      operation. Our youngest patient is 31 years old. Ten weeks after bilateral
      trapezium-implantation he went back to his full-time job as a construction
      worker.

PMID- 8144071
TI  - [Swanson prosthesis or resection arthroplasty? A comparative study].
AB  - Two different surgical methods for basal joint arthrosis (implantation of a
      Swanson condylar prosthesis and resection arthroplasty) are compared. The medium
      term results are roughly comparable. However, the indication for prosthesis
      implantation is much more limited than that of resection arthroplasty.

PMID- 8144072
TI  - [Abductor pollicis longus-repair in treating basal thumb joint arthrosis].
AB  - Between 1987 and 1990, we operated 32 hands of 30 patients for basal joint
      arthrosis. After extirpation of the trapezium, a part of the abductor pollicis
      longus is pulled through and wrapped around the flexor carpi radialis, similar to
      the Lundborg method. This creates a tendinous web, which supports the first
      metacarpal bone. Patient assessment revealed good to very good results with only
      one dissatisfied patient; the objective evaluation showed two thirds good and one
      third poor results, comparable to those of alternative methods of creation of a
      tendon web with the flexor carpi radialis (Weilby) or the extensor carpi radialis
      longus (Necking and Eiken). The essential point is a permanent distance between
      the base of the first metacarpal bone and both the scaphoid and the base of the
      second metacarpal bone under normal conditions as well as under loading.

PMID- 8144073
TI  - [Initial experience with the Meuli cementless total endoprosthesis of the wrist
      joint].
AB  - The indications and the technique of implantation will be shown, and the results
      concerning function, pain reduction, and manual strength three years after
      surgery presented. Complications arose in cases with poor fixation of the cup
      prosthesis due to poor bone quality of the carpus. Operative salvage procedures
      are still possible.

PMID- 8144074
TI  - [A simple external fixator of Kirschner wires and electric clips for use on
      fingers].
AB  - A simple external fixator is introduced made of Kirschner wires and electric
      clips. This external fixator has been used for fifteen years and has a number of
      indications: phalangeal fractures, infections, and cross-finger flaps.

PMID- 8144075
TI  - [A new external fixator for treatment of unstable distal radius fracture].
AB  - Unstable distal radius fractures cannot be immobilized in a plaster cast: mal
      unions (and later arthrosis of the wrist) are the result. Most symptoms are
      attributable to the shortening of the radius. Retention by means of an external
      fixator is the therapy of choice in such cases. Various fixator systems have
      become known. In this paper, a new fixator is presented which has the following
      advantages: It is very mobile and adaptable, and corrections are possible after
      attachment of the fixator. The screws can be inserted depending on the anatomical
      situation. The fixator is handy and light. The fixator has proved its
      effectiveness for a long time and is also suitable for complicated wrist
      injuries.

PMID- 8144076
TI  - [New osteosynthesis material in hand surgery].
AB  - Stable internal fixation is an important principle of treatment in hand surgery.
      Titanium implants have proven themselves suitable and successful. Form and
      variety of implants satisfy all the demands for internal fixation. A recently
      developed "osteo-chip-system" will simplify handling.

PMID- 8144077
TI  - [Results of follow-up examinations of treatment of Mantero flexor tendon injury
      in zone 1 and distal zone 2].
AB  - We did follow-up examinations of flexor tendon sutures of 161 digits in 151
      patients treated according to the Mantero-technique. They revealed that the
      urgence differee still has its merits today. The results of the sutures in zone 2
      correspond to those of zone 1, if only one tendon is affected (zone 2.1), while
      they are clearly inferior, when two tendons are involved (zone 2.2).

PMID- 8144078
TI  - [Slowly progressive aphasia].

PMID- 8144079
TI  - [Effects of corticosteroids on the metabolism of the trace element chromium].

PMID- 8144080
TI  - [Nobel prize winners in medicine--1993].

PMID- 8144081
TI  - [Laparoscopic-assisted colectomy].
AB  - After gaining experience in laparoscopic cholecystectomy, laparoscopic
      appendectomy and other laparoscopic procedures, we decided to perform
      laparoscopic-assisted colectomy. During July 1992 to February 1993 we performed
      14 such procedures. Ages ranged from 46-83 years (mean, 68). In all cases the
      indication for surgery was neoplasm of the colon. 8 of the tumors were located in
      the right colon and 6 in the sigmoid. Procedures performed were laparoscopic
      assisted right hemicolectomy with a biofragmentable anastomotic ring or
      laparoscopic-assisted sigmoidectomy with end-to-end anastomosis. In 1 operation
      we combined laparoscopic cholecystectomy with laparoscopic right hemicolectomy.
      Operation time varied from 90-130 min (mean, 100 min). In our opinion the
      procedure is as radical as standard laparotomy with the number of lymph nodes per
      specimen ranging from 4-10 (mean, 7); the surgical margins were free of tumor in
      all cases. There was less pain in the postoperative period than with the standard
      procedure and the average time from operation to discharge was 7 days (range, 5
      9). Complications included 1 fatality due to postoperative myocardial infarction,
      and 1 case of duodenal perforation which was sutured during the operation. We
      conclude that laparoscopic-assisted right hemicolectomy and laparoscopic
      sigmoidectomy are feasible for carcinoma, and that recovery is quicker and with
      less pain. However, we need a larger series and long-term follow-up to conclude
      whether the laparoscopic assisted technic is an adequate operation in cases of
      cancer.

PMID- 8144082
TI  - [Intra-operative cholangiography in laparoscopic cholecystectomy].
AB  - Intraoperative cholangiography (IC) in laparoscopic cholecystectomy is a
      controversial issue. According to traditional teaching, the purpose of
      cholangiography in gallbladder surgery is to discover previously undiscovered
      common bile duct stones. This examination was extremely important in the era
      before ERCP. IC enabled surgeons to find stones and remove them at the same
      operation. With progress in ERCP, the importance of intraoperative
      cholangiography has diminished. A stone missed during surgery can most often be
      dealt with by the less invasive ERCP and papillotomy. There has been a difference
      of opinion in the literature as to whether to perform cholangiography routinely
      during gallbladder operations or only in cases in which there is a specific
      indication, such as an enlarged common bile duct, a history of pancreatitis, or
      elevated enzymes. Routine operative cholangiography prolongs operative time and
      carries its own inherent risks, such as injury to the bile ducts. The likelihood
      of stones is not high and over-diagnosis of stones would result in unwarranted
      common bile duct exploration and the danger of complications from the procedure.
      The tendency today is towards a more selective approach. In this era of
      laparoscopic gallbladder surgery, the controversy has come to the fore again, and
      there is now an additional aspect. In laparoscopic gallbladder surgery there is
      greater significance to the "road map" provided by X-rays. We rely mainly on the
      visual sense and have forgone the tactile sense. Therefore, any added visual
      input in this operation helps avoid the danger of injuring the main bile ducts.
      It is our contention that the indications for operative cholangiography in
      laparoscopic cholecystectomy should again be broadened.

PMID- 8144083
TI  - [Effect of pterygium excision on keratometric readings].
AB  - A pterygium is a triangular, fibrovascular connective tissue overgrowth of bulbar
      conjunctiva onto the cornea. A pterygium may grow into the visual axis and thus
      obstruct vision. It may also have an effect on corneal curvature and cause
      irregular astigmatism or formation of dellen. No study of these effects after
      surgical treatment has been published, to the best of our knowledge. In this
      study an attempt was made to find out whether corneal curvature is affected as a
      result of the surgery. The results of 28 pterygium operations performed between
      1989-1990 were analyzed as regards k-readings before and 4 months after operation
      (1 month after discontinuance of thiotepa drops). It was found that excision of
      the pterygium by the bare sclera technique, together with the use of steroids and
      thiotepa drops, had no effect on the corneal k-readings made 4 months after
      operation.

PMID- 8144084
TI  - [Adamantinoma of the tibia].
AB  - Adamantinoma of the tibia is a rare, malignant growth originating in epithelial
      fetal cells. We present a 17-year-old girl who had prolonged pain in her right
      calf for 6 years. X-ray showed a growing malignant lesion whose nature was
      confirmed by biopsy. After planning the anatomical and functional aspects, the
      tibia was excised in its diaphyseal part, which included the growth with wide
      margins. Iliac bone was implanted in place of excised tibial bone. After 1 year
      the implant showed complete healing and had grown to impressive size, ensuring
      safe carrying of body weight, and the length and function of the limb were
      completely normal. 4 years postoperatively no pathologic lesion was noted on
      clinical examination, in X-rays nor in another biopsy of the implanted bone and
      the surrounding soft tissues.

PMID- 8144085
TI  - [Obstruction of the prostatic urethra by villous adenoma].
AB  - We report a case of a benign villous adenoma of the prostatic urethra causing
      urethral obstruction in a 45-year-old man. Villous adenoma of the prostatic
      urethra is rare. Hematuria was the presenting sign in most reported cases.
      However, some lesions were discovered unexpectedly on endoscopic examinations for
      the assessment of lower urinary tract disease. Villous adenoma of the urethra is
      composed of prostatic type tissue. The presence of the PSA marker in its
      epithelium indicates a common embryologic origin with the prostate.

PMID- 8144086
TI  - [Brucella orchitis].
AB  - Brucellosis is a multi-organ infectious disease which affects the genito-urinary
      system in 2-10% of cases, mainly as orchitis. There have been very few reports in
      Israel of genito-urinary system involvement in patients with brucellosis,
      possible due to a low index of suspicion. Identification of brucella orchitis
      would result in proper medical treatment, thus preventing unnecessary surgery. We
      present a case of brucella orchitis, highlighting the place of brucellosis in the
      differential diagnosis of orchitis.

PMID- 8144087
TI  - [Tetanus--the forgotten disease].
AB  - Tetanus is preventable by proper immunization, which has almost eradicated the
      disease in countries with a high standard of living. However, the disease is
      still prevalent even in the most advanced countries and it often appears in the
      elderly. We emphasize this fact and alert primary care physicians, and duty
      physicians in emergency rooms, to the possibility of tetanus developing in older
      patients. Because of their age, they often do not remember when they last had
      tetanus immunization, nor are records always adequate. We point out the necessity
      and feasibility of incorporating a special immunization review program for the
      elderly, including a cost-benefit analysis.

PMID- 8144088
TI  - [Prenatal diagnosis--update].

PMID- 8144089
TI  - [Recurrent abortions--update].

PMID- 8144090
TI  - [Electroconvulsive treatment: the right to accept versus the right to refuse:
      critique and suggestions for legislative changes].

PMID- 8144091
TI  - [Motor-evoked potentials].

PMID- 8144092
TI  - [Animal metamorphosis (lycanthropy) still exists].

PMID- 8144093
TI  - [General thoracic surgery--where to?].

PMID- 8144094
TI  - [The modern approach to the diagnosis and treatment of sinusitis].

PMID- 8144095
TI  - [Avoiding risks of unnecessary blood transfusion in surgical patients].

PMID- 8144096
TI  - Ensheathing cells in the nerve fiber layer of the olfactory bulb--a novel glial
      cell type.
AB  - Olfactory nerve ensheathing cells (ONECs) were originally described as Schwann
      cells of the olfactory nerve. More recent studies have suggested that these cells
      express features of astrocytes, including the lack of basal lamina and collagen
      fibrils and the failure to ensheath axons individually. Recently performed
      experimental studies showed that ONECs from the olfactory bulb represent a novel
      glial cell type.

PMID- 8144097
TI  - The number of mitral cells in the adult human olfactory bulb.
AB  - The number of mitral cells in layer III and IV was investigated in 8 olfactory
      bulbs removed from adult humans aged 21, 23, 41, and 42 years. This number was
      highest in male aged 23 years and in 41 and 43 years old specimens it decreased
      to the level found in 21 years old female.

PMID- 8144098
TI  - Ultrastructure of the ram pinealocytes during breeding season in natural short
      and in artificial long photoperiods.
AB  - The study was performed from 20th September to 20th October on eight Polish
      Longwool rams, variety Pomorska (Pomeranian), aged 33 months, which were divided
      into two equal groups. The animals of control group were kept in natural
      photoperiod. The experimental group was maintained during 30 days in controlled
      lighting conditions (16L: 8D). On the thirtieth day of the experiment the animals
      were slaughtered between 1000h and 1200h. The pineal glands were prepared for EM.
      Point count analysis was employed to estimate the relative volumes of pinealocyte
      organelles. The increase of relative volumes of mitochondria and lipid droplets
      in comparison to the control was observed in the experimental group. There were
      also some qualitative changes in organization of granular endoplasmic reticulum
      and microtubules.

PMID- 8144099
TI  - Types of interventricular septal branches of the anterior interventricular branch
      of the left coronary artery in human hearts.
AB  - The study aimed at determining types of interventricular septal branches stemming
      from the anterior interventricular branch of the left coronary artery. The
      studies were performed on 28 preparations of human heart aging 29 to 88 years.
      The technique of direct preparation was applied using a dissecting microscope.
      The conducted observations indicate that septal vessels of the anterior
      interventricular branch follow one of the three main patterns. Type I involves a
      dominant septal trunk, exhibiting its own branching and few fine septal branches,
      type II exhibits a single dominant unbranched ramus and multiple fine branches,
      while type III includes two dominant, unbranched septal rami of the septum and
      small number of fine septal branches. In the cases examined by us type III
      pattern was most frequent. No relationship was detected between the type of
      coronary vessels of the heart and the type of septal vessels of the anterior
      interventricular branch.

PMID- 8144100
TI  - Adrenergic and acetylcholinesterase-positive innervation of the bovine oviduct.
AB  - Adrenergic and cholinesterase-positive (AChE-positive) innervation of the bovine
      oviduct was studied using histochemical methods. Both subpopulations of the
      studied nerve fibres were found in the isthmus, ampulla and infundibulum where
      they were mainly related to the muscular coat or blood vessels of the organ. The
      adrenergic innervation was found to be much better developed than the cholinergic
      one. Adrenergic and cholinergic nerves were numerous in the isthmal port of the
      Fallopian tube, whereas these fibres were less numerous in the ampulla. The
      infundibulum contained the smallest number of adrenergic and ACHE-positive nerve
      fibres.

PMID- 8144101
TI  - Blood vessels of epineurium of ischaidic nerve in the man.
AB  - Blood vessels were examined within epineurium of 38 ischiadic nerves from corpses
      of men and women aging 26 to 65 years. The studies demonstrated that large
      eyeholed and fine meshed vascular plexuses are formed in both components of
      ischiadic nerve. The plexus maintain communication with axial arterial and venous
      vessels which run in the outer layer of epineurium and with interfascicular
      vessels located in connective tissue of interfascicular epineurium.

PMID- 8144102
TI  - [Effects of pranidipine (OPC-13340), a novel 1,4-dihydropyridine derivative Ca
      antagonist, on isolated porcine coronary contraction and acute myocardial
      ischemia in the pig].
AB  - Pranidipine (OPC-13340) is a novel, potent and long-acting 1,4-dihydropyridine
      derivative Ca-antagonist being developed for clinical use as an antihypertensive
      and antianginal drug. Pranidipine at concentrations of 10(-9) - 10(-6) M
      suppressed the contraction induced by serotonin (10(-8) - 10(-5) M) or histamine
      (10(-8) - 10(-4) M) in isolated porcine coronary arteries in a non-competitive
      and concentration-dependent manner. The potency of this effect of pranidipine was
      almost similar to that of nifedipine. In anesthetized open-chest pigs with
      coronary artery occlusion, pranidipine at a dose of 10 micrograms/kg, i.v.
      lowered blood pressure and increased heart rate, peak dP/dt and % segment
      shortening of the non-ischemic zone before occlusion. Pranidipine inhibited the
      ST elevation of the electrocardiogram and the increase in left ventricular end
      diastolic pressure during ischemia. These results suggest that pranidipine might
      relieve symptoms via inhibition of coronary spasm and reduce myocardial ischemia
      due to reduction of both preload (left ventricular end-diastolic pressure) and
      afterload (blood pressure).

PMID- 8144103
TI  - [Acidified aspirin-induced gastric lesion in rats with hepatic cirrhosis produced
      by N-nitrosodiethylamine or carbon tetrachloride. Effect of aldioxa on gastric
      lesions].
AB  - Gastric lesion was induced by the oral administration of acidified aspirin in
      rats with hepatic cirrhosis produced by N-nitrosodiethylamine (NDA) or carbon
      tetrachloride (CCl4). Gastric lesion by acidified aspirin was aggravated in NDA
      induced cirrhosis, but not in CCl4-cirrhotic rats. To clarify this difference in
      the susceptibility of the gastric mucosa, gastric mucosal blood flow and gastric
      emptying were measured by the hydrogen gas clearance method and beads method,
      respectively. Gastric mucosal blood flow was lower and gastric emptying was
      significantly delayed in NDA-induced cirrhotic rats as compared with the
      controls, but not in CCl4-induced cirrhotic rats. Gastric mucosal blood flow in
      NDA-induced cirrhotic rats was significantly decreased by the oral administration
      of acidified aspirin as compared with the controls. Aldioxa dose-dependently
      inhibited the gastric lesion formation by acidified aspirin and inhibited the
      decrease of gastric mucosal blood flow in NDA-induced cirrhotic rats. These
      results suggest that aggravation of gastric lesion induced by acidified aspirin
      in NDA-induced cirrhotic rats would be due to the decrease of gastric mucosal
      blood flow and delay of gastric emptying. In addition, aldioxa showed a
      protective effect against gastric lesions induced by acidified aspirin in NDA
      induced cirrhotic rats, suggesting that this compound would have an inhibitory
      effect on gastric lesions that are accompanied by hepatic cirrhosis.

PMID- 8144104
TI  - [Methods for studying an isolated renal microvessel].
AB  - Glomerular circulation is mainly regulated by two resistance arterioles, the
      afferent arteriole and the efferent arteriole. Many experimental findings show
      that each arteriole has a different sensitivity to various kinds of physiological
      stimuli and some vasoactive substances. Moreover, there is a regional
      heterogeneity of the glomerular microcirculation. Thus, many researchers have
      been challenged to develop direct studies that focus on the control of the renal
      microcirculation. The recent development of innovative in vivo and in vitro
      preparations provide the opportunity to directly study the renal
      microcirculation. In this article, we introduce the methods for isolation,
      cannulation and in vitro study of a single renal arteriole. The isolated renal
      microvessel technique permits direct in vitro assessment of single arteriolar
      responses in defined segments to vasoactive substances without the neurohumoral
      and parenchymal tissue environment. Intracellular ion concentration and
      functional change of the renal microvessel can be evaluated simultaneously using
      both this technique and fluorescent ion indicators. Accumulation of data that
      directly assesses the renal microcirculation may clarify mechanisms for the
      regulation of renal hemodynamics.

PMID- 8144105
TI  - [Bronchial hyperresponsiveness to histamine induced by intravenous administration
      of 13,14-dihydro-15-keto-prostaglandin F2 alpha in guinea pigs].
AB  - Prostaglandin F2 alpha (PGF2 alpha) has been suggested to play a role in the
      pathogenesis of bronchial asthma. In this study, the effects of intravenous
      administration of 13,14-dihydro-15-keto-PGF2 alpha, a stable metabolite of PGF2
      alpha, on bronchial smooth muscle in guinea pigs were investigated by measuring
      dynamic respiratory resistance using a formula that excludes the effects of
      differences in airway wall thickness. With this formula, the ratio of bronchial
      smooth muscle constriction by histamine can be estimated as an index of bronchial
      hyperresponsiveness. Administration of 13,14-dihydro-15-keto-PGF2 alpha did not
      induce airway wall edema. The ratio of bronchial smooth muscle constriction by
      histamine was significantly enhanced by the administration of 13,14-dihydro-15
      keto-PGF2 alpha. Moreover, TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited
      the effect of 13,14-dihydro-15-keto-PGF2 alpha administration. These results
      suggest that 13,14-dihydro-15-keto-PGF2 alpha can be important mediators
      affecting bronchial hyperresponsiveness, and TXA2 may play a part in the 13,14
      dihydro-15-keto-PGF2 alpha-induced bronchial hyperresponsiveness.

PMID- 8144106
TI  - Chemical composition of baboon plant foods: implications for the interpretation
      of intra- and interspecific differences in diet.
AB  - Information on the chemical composition of baboon foods from the Laikipia
      Plateau, Kenya, is presented. Despite some differences in methods, results of
      analyses performed on the same foods at different sites were found to be
      extremely consistent, encouraging the view that meaningful intra- and
      interspecific comparisons of diet selection are feasible. Contrary to assumptions
      in the literature, no relationship between the abundance of food types and their
      chemical composition was found, nor was the foliage eaten by the baboons found to
      be a low-quality or high-fibre item in comparison with fruits and storage organs.
      Emphasis is placed on the need for caution in the use of simplistic dietary
      taxonomies which imply phytochemical and ecological homogeneity within broad food
      categories. Comparisons between three species revealed marked differences in the
      chemical composition of their diets; in particular, baboon diets were found to be
      higher in protein and lower in fibre than those of either lowland gorillas or
      Malaysian leaf monkeys, and differences in condensed tannin levels were also
      found. The relationship between these differences and the socio-ecology of the
      three species is discussed.

PMID- 8144107
TI  - Ecology of female social relationships: Hanuman langurs (Presbytis entellus) and
      the van Schaik model.
AB  - The ecological model of Carel van Schaik provides clear predictions for female
      female relationships in relation to scramble or contest within-group competition
      and contest between-group competition. These predictions were applied to data
      from a 12-year field study on Hanuman langurs (Presbytis entellus) that ranged
      freely around Jodhpur (India). It appears that hierarchical relationships between
      females (unstable, inconsistent, individualistic, with low rates of agonistic
      coalitions) reflect scramble within-group competition. Such competition, however,
      results in individual evolutionary advantages (differential feeding time;
      differential reproductive success) so that dominance effects mirror contest
      within-group competition. Between-group contest competition at Jodhpur is strong
      (low predator pressure, high population density, good food defensibility,
      essential role of females during intergroup encounters, loud vocalization of
      males). The results are discussed in the light of langur feeding habits.

PMID- 8144108
TI  - Defining subgroup size in fission-fusion societies.

PMID- 8144109
TI  - Gut passage rate in guenons and mangabeys: another indicator of a flexible
      feeding niche?

PMID- 8144110
TI  - Hand preference in the use of nut-cracking tools by tufted capuchin monkeys
      (Cebus apella).

PMID- 8144111
TI  - Evolution of the sociosexual pattern of the stumptail macaque (Macaca arctoides).

PMID- 8144112
TI  - Promoting increased foraging behavior in caged stump-tailed macaques.

PMID- 8144113
TI  - Tail-wagging as a tension relief mechanism in pithecines.

PMID- 8144114
TI  - Bilateral retention of deciduous canines in an olive baboon.

PMID- 8144115
TI  - [Is ultrasound screening in pregnancy still valid? Doubt in recent studies].

PMID- 8144116
TI  - [Anticoagulation in non-rheumatic atrial fibrillation. Recommendations based on
      five prospective studies].
AB  - Atrial fibrillation is the second most common arrhythmia after ventricular
      premature beats. For years, prophylactic anticoagulation has been recommended in
      patients with atrial fibrillation in underlying rheumatic heart disease. With the
      aim of establishing the risk of embolism in non-rheumatic atrial fibrillation,
      and the justification for prophylactic anticoagulation therapy, five prospective
      studies were carried out. The results obtained indicate that all patients with
      chronic atrial fibrillation should receive anticoagulation therapy wherever
      possible (INR 2.0 to 3.0). The sole exception are patients aged under 55 years
      with no other organic heart disease. For this group, the risk of a stroke is
      appreciably reduced, so that treatment with ASA suffices.

PMID- 8144117
TI  - [Current developments in gastrointestinal endoscopy. Part 3: Small intestine-
      large intestine].

PMID- 8144118
TI  - [Prevention before foreign travel. Part 1: Vaccinations].

PMID- 8144119
TI  - [Successful combination therapy in bronchial asthma. Anti-obstructive and anti
      inflammatory treatment].
AB  - METHOD: In a post-marketing surveillance study, patient data were documented with
      the aim of assessing the effect of a combination of both anti-inflammatory and
      bronchodilatory treatment with inhaled beclomethasone dipropionate and a
      sustained-release theophylline preparation. A total of 2,166 patients with mild
      to-moderate bronchial asthma (FEV1 about 60%) were included in the multicenter
      open study. RESULTS: It was found that treatment with inhaled glucocorticoid and
      sustained-release theophylline resulted in a clear improvement in symptom scores.
      More than 90% of the physicians and patients rated the treatment "very good" or
      "good". Only 4.6% of the participants had side effects. CONCLUSION: It may be
      concluded that combination therapy with inhaled glucocorticoid and sustained
      release theophylline is a safe and effective form of treatment of mild-to
      moderate asthma.

PMID- 8144120
TI  - [What are the indications for proton pump inhibitors? R. Arnold, Marburg,
      elaborates on the clinical aspects of the controversy regarding lansoprazole.
      Interview by Gerrit Lichtenberg].

PMID- 8144121
TI  - [Controlling blood pressure by centrally acting drugs--still a topic?].

PMID- 8144122
TI  - [Bronchial hyperreactivity and obstructive respiratory tract diseases. A 2.8 year
      follow-up study].
AB  - BACKGROUND: Nonspecific bronchial hyperreactivity (BHR) is under discussion as a
      possible risk factor for the development of chronic obstructive pulmonary
      disease. METHOD: Within the framework of a prospective study, we investigated the
      course of the disease in 50 inpatients with BHR, and the clinical symptoms of
      airways disease (coughing, dyspnea and expectoration) with no manifest airways
      obstruction at rest (Rt < 3.5 cm H2O/l/s) on admission to the hospital. The
      unspecific inhalative provocation challenge was carried out with metacholine. The
      presence of BHR was assumed when the resting respiratory resistance (Rt) of < 3.5
      cm H2O/l/s increased to more than 6 cm H2O/l/s. On admission to hospital, all the
      patients were treated with inhalative bronchodilators and glucocorticosteroids.
      RESULTS: After an average period of 2.8 years, BHR was no longer measurable in
      only 7 of the patients (14%), while 28 patients (56%) continued to have a BHR
      with clinical symptomatology presenting. In 15 patients (30%), manifest airways
      obstruction at rest, with an average Rt of 6.4 cm H2O/l/s developed. In patients
      with an uncharacteristic cough, dyspnea and unremarkable lung function parameters
      at rest, a provocation test should be done to identify BHR. A prognosis can,
      however, not be established on the basis of a single demonstration of BHR, but
      only after observation over a longer period.

PMID- 8144123
TI  - [Virus infections--disease manifestations and laboratory diagnosis. Part 6: Mumps
      virus--respiratory syncytial virus (RSV)].

PMID- 8144124
TI  - [The nephroprotective effect of ramipril. Effect on blood pressure and metabolic
      control in insulin-treated patients with type-2 diabetes mellitus].
AB  - AIM: Investigation of the impact of blood pressure and metabolic control on the
      nephroprotective effect of ramipril in insulin-dependent diabetics. METHOD:
      Within the framework of an open prospective therapeutic trial, 18 hypertensive,
      insulin-treated diabetics received ramipril, 5 mg/day, for an average period of
      11 months. All the patients had previously received various forms of
      antihypertensive medication, and had microalbuminuria. RESULTS: Urinary excretion
      of albumin and N-acetyl-beta-D-glucosaminidase decreased in 13 patients (group
      1), but increased in the remaining five patients (group 2). Blood pressure
      clearly decreased in group 1, but remained constant in group 2. In terms of
      clinical and biochemical data, the group 2 patients differed from those in group
      1, having a lower age, a shorter history of diabetes and higher hemoglobin A1c
      levels despite higher doses of insulin. CONCLUSIONS: The present observations
      show that inadequate metabolic control and refractory hypertension in type 2
      diabetics accelerate progression of diabetic nephropathy, and may thus negate the
      nephroprotective effect of the converting enzyme inhibitor, ramipril.

PMID- 8144125
TI  - [Personality traits and vulnerability markers--problems of assessment].
AB  - Personality traits play an increasing role in research on the vulnerability to
      mental disorders. Problems of their assessment are dealt with here with special
      reference to work of our own in this area. Personality inventories for self
      rating or informants' rating are appropriate instruments for retrospective as
      well as prospective investigations. They should be short and, at the same time,
      suites for the assessment of the main dimensions of personality, the "Big Five".
      The Munich Personality Test (MPT) and the Six Factor Test (SFT) serve as examples
      in this context. They were already successfully applied in clinical and
      outpatient settings and in "high-risk" studies. In retrospective investigations,
      a newly developed method for the operationalized diagnosis of personality types
      from case history data can be used as well. On the basis of this approach, we
      have recently developed a Biographical Personality Interview (BPI) which, in
      combination with personality inventories, can be regarded an optimal device for
      the assessment of premorbid personality in psychiatric patients.

PMID- 8144126
TI  - [Modification of sexual functions by antidepressants].
AB  - Sexual dysfunctions appear to be frequently occurring adverse events in treatment
      with antidepressants. Due to methodological reasons, a reliable estimation of the
      frequency of such events is currently not yet possible. There is evidence, that
      antidepressants could be differentiated with respect to their potency and
      specificity for disturbances of certain sexual subfunctions according to their
      pharmacological profile. With SSRIs in particular impaired functions of orgasm
      and ejaculation can be observed. No deteriorations are reported for buproprion
      and an improvement of sexual dysfunctions within the course of treatment for
      moclobemide. Viloxazine and trazodone appear to possess marked stimulating
      effects on libido and erectile functions. Generally the incidence of sexual
      adverse events is underestimated, although there is a pronounced impact on
      patient compliance. Taking into account this well documented side effect, sexual
      impairments should be monitored carefully within antidepressive treatment.

PMID- 8144128
TI  - The association of myasthenia gravis and connective tissue diseases--the role of
      Sjogren's syndrome.
AB  - The symptoms of myasthenia gravis (MG) reflect the loss of neuromuscular
      transmission due to the functional loss of the acetylcholine receptor. We
      reviewed the reported association of MG and connective tissue diseases including
      rheumatoid arthritis, systemic lupus erythematosus, progressive systemic
      sclerosis (PSS), polymyositis and dermatomyositis, mixed connective tissue
      disease (MCTD) and Sjogren's syndrome (SjS). We found that the association of MG
      and MCTD or PSS is rare. We also reviewed the role of D-penicillamine, thymus
      abnormalities and the coexistence of SjS as one of the underlying pathological
      conditions for the association of MG and various connective tissue diseases.

PMID- 8144127
TI  - [Do estrogens have an antipsychotic action?].
AB  - Within the framework of our ABC study, an epidemiological study on schizophrenia
      (Hafner et al., 1989, 1991 a; Riecher et al., 1991), we were able to show that
      the mean age at onset of the disease is 3-4 years higher in women than in men and
      that women have a second peak of onsets after 45 years of age. In a systematic
      analysis we developed and tested different psychosocial and biological explantory
      hypotheses. The oestrogen hypothesis could be identified in the course of this
      analysis as the most plausible one. According to this hypothesis (Hafner, 1987)
      female sex hormones enhance the vulnerability threshold for schizophrenia. In
      this case women from puberty to (pre-)menopause would be protected from the
      outbreak of the disease to a certain extent by their high physiological
      oestradiol production; they would, however, later "draw level" in respect of
      morbidity risk. Animal experiments conducted to test this hypothesis and to
      explain the underlying pathophysiological mechanism implied that oestradiol can
      modulate the sensitivity of dopamine-D2-receptors in the brain (Hafner et al.,
      1991 b; Gattaz et al., 1992). In the clinical study presented, we examined the
      validity of the oestrogen hypothesis in humans. We tested, whether the acute
      symptomatology of schizophrenic patients fluctuates with oestradiol serum levels
      during the female menstrual cycle. We examined 32 acutely admitted schizophrenic
      women during their hospital stay by analysing hormonal parameters and applying
      various rating scales for psychopathology on certain days of the cycle. A
      significant association emerged between oestradiol levels on the one hand, and
      psychiatric symptomatology, behaviour on ward, paranoid tendencies and general
      well-being, on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144129
TI  - Detection of minimal residual disease in a patient with acute promyelocytic
      leukemia by RT-PCR: necessity of chemotherapy following ATRA therapy.
AB  - The PML/RAR alpha fusion gene resulting from the t (15;17) translocation is a
      specific marker for acute promyelocytic leukemia (APL). We examined bone marrow
      cells by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect
      residual PML/RAR alpha mRNA-containing cells following treatment with all-trans
      retinoic acid (ATRA) and cytotoxic chemotherapy in a patient with APL. This RT
      PCR assay can detect one leukemic cell in 10(2) normal cells in vitro. We show
      that PML/RAR alpha mRNA was still detectable despite clinical remission following
      ATRA treatment, but undetectable following consolidation with chemotherapy. These
      data show that this technique is useful for the identification of minimal
      residual disease in patients with APL and that cytotoxic chemotherapy following
      ATRA therapy is required for the elimination of APL cells.

PMID- 8144130
TI  - [Quantitative analysis of the binding of peptides to HLA molecules role of
      polymolphic HLA molecules in the immune response].
AB  - We established HLA-peptide binding assay system, using biotinylated peptide and
      HLA class II transfectants to make clear the interaction of peptides and HLA
      molecules. By using this system and T cell proliferation assay, we analyzed the
      effect of polymorphism of DR4 subtypes on responding to M12(4) peptide which
      derived from M12 protein of Streptococcus. We found amino acid residue which
      determines T cell recognition is DR beta-74 (Glutamate to Alanine) on this
      peptide. Using this system, we expect to understand the mechanisms of immune
      response associated with HLA class II molecules.

PMID- 8144131
TI  - Reinforced HEAV'D therapy for adult acute lymphoblastic leukemia: improved
      results and revised prognostic criteria.
AB  - Thirty-six adults with acute lymphoblastic leukemia (ALL) were treated with
      adriamycin, vincristine, prednisolone, and asparaginase for remission induction,
      followed by vincristine-adriamycin-cyclophosphamide consolidation courses,
      cranial irradiation, a short ara-C plus VM-26 pulse, and vincristine plus
      cyclophosphamide rotating weekly with ara-C plus VM-26 for three months
      (reinforced HEAV'D). Thirty-one patients achieved a complete remission (86 per
      cent). Compared with historical results from a prior study, age > 30 years,
      absolute blast count > 15 x 10(9)/l, and CD10-negative immunophenotype were not
      associated with higher relapse rate and shorter survival, suggesting a positive
      effect from intensification therapy with ara-C and VM-26 in these poor prognostic
      categories. However, patients with an abnormal karyotypic pattern or a positive
      molecular study for BCR-ABL rearrangement detecting t(9;22) had a far greater
      likelihood of treatment failure (probability of remission at 3 years 0.10) than
      those with normal karyotype or negative molecular study (probability 0.70), and
      those not studied or with insufficient methaphases (probability 0.50) (p < 0.05
      by log-rank test). These results underline the prognostic importance of
      chromosomal abnormalities and the usefulness of ara-C and VM-26 in the management
      of adult ALL.

PMID- 8144132
TI  - Recombinant interferon-alpha 2b and high dose methyl prednisolone in relapsed and
      resistant multiple myeloma.
AB  - Twenty-one patients with refractory myeloma (10 primary resistant and 11 relapsed
      resistant) were treated with a combination of high dose methyl prednisolone and
      recombinant interferon alpha 2b (IFN-alpha 2b). This treatment included three
      megaunits/m2 of IFN-alpha 2b three times a week for 12 weeks, plus 5-day pulsed
      high dose methyl prednisolone every 3 weeks for two courses. A partial response
      (more than 50 per cent reduction in paraprotein) was observed in six patients;
      two of these had a greater than 75 per cent reduction in paraprotein, and
      evaluation of bone marrow showed <5 per cent plasma cells. A minimal response
      (more than 25 per cent reduction in paraprotein) was seen in four patients,
      giving an overall objective response rate of 10/21 (48 per cent). Subjective
      response, in terms of subsidence of pain and improvement of performance status,
      was seen in all patients who had adequate therapy. The protocol was generally
      well tolerated with minimal side-effects. There were 4/21 (19 per cent) treatment
      related deaths which, though considerable, was anticipated in such a study
      population. The excellent subjective response seen supplements the objective
      response observed, and suggests a potential role for the combination of methyl
      prednisolone and IFN-alpha 2b in refractory myeloma.

PMID- 8144133
TI  - Infiltration of eosinophils in Hodgkin's disease involved lymph nodes predicts
      prognosis.
AB  - The number of infiltrating eosinophils were counted in tumour specimens from an
      unselected material of 140 cases of primary Hodgkin's disease (HD) and divided in
      three groups. Twenty-six cases (19 per cent) showed heavy infiltration (> 200
      eosinophils/10 vision fields (VF)), 51 (36 per cent) moderate infiltration (11
      200 eosinophils/10 VF and 63 virtually no infiltration (< 10 eosinophils/10 VF).
      The eosinophilic infiltration was significantly more pronounced in the nodular
      sclerosis subtype. Cases with heavy infiltration had a significantly worse
      disease-free survival compared to other cases. In a multivariate analysis, heavy
      eosinophilic infiltration was the most important factor for determining disease
      free survival in all patients and also when patients above and below 60 were
      analysed separately.

PMID- 8144134
TI  - Correlation of immunological surface antigens with survival in diffuse large cell
      lymphoma.
AB  - The prognostic value of immunophenotyping lymphomas with a panel of monoclonal
      antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases
      of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry
      after labelling by indirect immunofluorescence. Thirty-eight cases were
      demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis
      demonstrated that survival was significantly longer in patients expressing higher
      levels of HLA-DR (p = 0.01) and normal levels of CD8 (p = 0.04) but was not
      significantly associated with any of the other antigens. Our results support the
      possible value of HLA-DR in determining the prognosis of patients with diffuse
      large cell lymphoma.

PMID- 8144135
TI  - Current awareness in hematological oncology.

PMID- 8144136
TI  - Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type in Waldeyer's
      ring.
AB  - Amongst a total of 329 cases of low-grade B-cell lymphoma of Waldeyer's ring, we
      identified 12 cases that corresponded histomorphologically to low-grade B-cell
      lymphoma of mucosa-associated lymphoid tissue (MALT) type. These lymphomas are
      characterized by an extrafollicular growth pattern, often with a marginal zone
      like arrangement, and by the centrocyte-like morphology of the tumour cells. They
      have not been described previously in this location. They predominantly affected
      the palatine tonsil. Ten cases were primary lymphomas of Waldeyer's ring. In two
      cases there was a simultaneous high-grade component. Two cases showed regional
      spread to cervical lymph nodes, but there was no widespread nodal involvement at
      the time of diagnosis. Immunohistochemically, all cases displayed B-cell markers
      and light chain restriction. Tropism of tumour cells for the epithelium was a
      consistent finding. In two cases involvement of Waldeyer's ring was secondary; in
      one of them the primary tumour was a gastric low-grade B-cell lymphoma of MALT
      type and in the other a high-grade B-cell non-Hodgkin's lymphoma of the stomach.
      These findings indicate that low-grade B-cell lymphomas of MALT type occurring in
      Waldeyer's ring should be included amongst the tumours of the MALT system. We
      surmise that in Waldeyer's ring such tumours are derived from the marginal zone,
      as has already been postulated for similar gastric tumours.

PMID- 8144137
TI  - Histopathology of transcervical resection of the endometrium.

PMID- 8144138
TI  - The bone marrow trephine biopsy.

PMID- 8144139
TI  - Adenomatous hyperplasia of rete testis.

PMID- 8144140
TI  - Waldeyer ring lymphomas. A clinicopathological study of 79 cases.
AB  - Waldeyer ring lymphomas belong to a category of tumours which has not yet been
      fully defined. Their relation to mucosa-associated lymphoid tissue (MALT) and
      other extranodal lymphomas remains largely unknown. We performed a
      clinicopathological retrospective study of 79 patients, and compared them with a
      series of MALT and nodal lymphomas. Tumours from the nasopharynx and palatine
      tonsil showed similar histological profiles, with a predominance of large B
      cells. Centroblastic lymphomas constituted the largest group (n = 45), followed
      by those of centrocytic type (9) with smaller groups of centroblastic-centrocytic
      (5) and Hodgkin's lymphomas (2). Three monocytoid B-cell lymphomas were
      identified. Only one case could be classified as MALT lymphoma. The frequency of
      bcl-2 expression in large B-cell tumours of Waldeyer's ring has an intermediate
      range between large B-cell lymphomas occurring in mucosal and nodal locations.
      Epitheliotropism was present in all low-grade cases, and was therefore not a
      useful marker in the identification of potential MALT lymphomas in contrast with
      other mucosal sites. Comparative survival studies showed significant overall
      differences between Waldeyer ring lymphomas, MALT and nodal cases. These
      disappeared after taking stage and histological grade into account. We conclude
      that Waldeyer ring lymphomas show distinctive features, mainly in terms of
      histological distribution and immunophenotype. The key factor determining their
      behaviour could be their different spreading capability. These findings suggest
      that extranodal lymphomas are heterogeneous, and indicate the need for additional
      efforts to clarify this.

PMID- 8144141
TI  - Pathological prognostic factors in breast cancer. III. Vascular invasion:
      relationship with recurrence and survival in a large study with long-term follow
      up.
AB  - The invasion of vascular spaces (lymphatic and/or blood vessel) by tumour, as
      assessed on routine haematoxylin and eosin sections, was investigated in a
      consecutive series of 1704 women with primary operable invasive breast carcinoma.
      Strict morphological criteria were used. Patients were under 70 years of age and
      received definitive surgery with no adjuvant systemic therapies. Information from
      regular follow-up (range 3-17 years) was recorded on to a computer database.
      Definite vascular invasion was seen in 22.8% of cases and concurrence between
      pathologists was high. In univariate analyses, vascular invasion was strongly
      associated with lymph node stage (P < 0.0001), tumour size (P < 0.0001),
      histological grade (P < 0.0001) and type of tumour (P < 0.0001). In multivariate
      analyses vascular invasion was of independent prognostic significance for both
      survival and for local recurrence of tumour; patients with tumours showing no
      vascular invasion had a significant survival advantage and a reduced risk of
      local recurrence. No association with oestrogen receptor status or menopause
      status was seen. The results confirm that histological assessment of vascular
      invasion provides independent prognostic information in primary operable breast
      carcinoma which may be helpful in making clinical decisions.

PMID- 8144142
TI  - Immunocytochemical localization of oestrogen and progesterone receptors in
      primary adenocarcinoma of the cervix.
AB  - Archival material from 47 primary invasive adenocarcinomas of the uterine cervix
      was examined using an immunocytochemical technique for detection of oestrogen
      receptor and progesterone receptor in paraffin-wax embedded tissues.
      Immunostaining for oestrogen receptor was noted within tumour cells in 12
      cervical adenocarcinomas while 13 tumours contained progesterone receptor. Eleven
      cervical adenocarcinomas expressed both oestrogen and progesterone receptor
      simultaneously. There was no association between steroid receptor status and
      major histological subtype, grade of tumour, clinical stage or age of patient at
      presentation. However, oestrogen receptor immunoreactivity was associated with
      disease-free survival. This preliminary study raises the possibility that, as in
      breast carcinoma, steroid receptor status may be a useful prognostic factor in
      adenocarcinoma of the cervix.

PMID- 8144143
TI  - Immunocytochemical and serological expression of CA 125: a clinicopathological
      study of 40 malignant ovarian epithelial tumours.
AB  - Elevated serum levels of the tumour-associated antigen CA 125 occur in more than
      80% of cases of ovarian carcinoma. The antigen can be demonstrated in formalin
      fixed tissue using the monoclonal antibody OC 125, which localizes it to the
      surface membrane or cytoplasm. This study was performed to determine the
      relationship between pre-operative serum levels of CA 125 and the subsequent
      immunocytochemical findings in the surgical specimen. Paraffin-wax embedded
      sections from 40 consecutive borderline and frankly malignant ovarian epithelial
      tumours were stained with OC 125. The pattern and distribution of immunostaining
      were investigated in relation to histological appearances. Serous tumours showed
      a 100% correlation between immunocytochemical findings and elevated serum levels
      of CA 125. Amongst the other histological types, correlation was less good;
      mucinous tumours and undifferentiated carcinomas showed a poor correlation.
      Immunostaining within tumours was heterogeneous and only loosely related to
      morphological appearances. Our finding suggests that, with the exception of
      serous tumours, immunolocalization of CA 125 is insufficiently sensitive to
      provide reliable clinical guidance to the likely value of serum CA 125 monitoring
      on follow-up.

PMID- 8144144
TI  - Pathology of shigellosis and its complications.
AB  - One hundred and thirty-three colonic biopsies of proven cases of Shigella colitis
      were examined and post-mortem examinations were carried out on 29 fatal cases at
      the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)
      hospital between 1988 and 1992. The distribution of pathological lesions and the
      spectrum of histopathological changes in the intestinal tract of these patients,
      and the features of intestinal and extra-intestinal complications of shigellosis
      are presented. Septicaemia, hyponatraemia, hypokalaemia and hypoglycaemia were
      present in a high percentage of these cases. All but two patients were
      malnorished at the time of autopsy. Shigellosis patients rapidly became
      hypoproteinaemic and were susceptible to other infections including opportunistic
      infections. Mortality amongst shigellosis patients admitted to our hospital
      continues to be high in spite of adequate antibiotic and supportive therapy.

PMID- 8144145
TI  - Expression of BCL-2 in the developing human fetal and infant breast.
AB  - The expression of BCL-2 protein was analysed in 10 fetal and 45 infant breast
      specimens by immunocytochemical staining of methacarn-fixed, paraffin-embedded
      tissue. In the developing fetal breast bud, BCL-2 was expressed in the basal cell
      layer and in the surrounding mesenchyme. Basal cells of epithelial buds destined
      to become hair follicles also expressed BCL-2 while the basal cell layer of the
      epidermis was negative. In infant breasts studied (aged 0-2 years), there was
      heterogeneous staining of the luminal epithelial cells of the ducts and lobules
      and no staining of myoepithelial cells or fibroblasts. The intensity of staining
      had a strong positive correlation with the age of the infant. Although the
      function of the bcl-2 gene in epithelial cells is unknown, these findings suggest
      that bcl-2 has a role in the morphogenesis of the human breast, and may help to
      sustain active epithelial-mesenchymal interaction by inducing longevity of
      certain cells.

PMID- 8144146
TI  - Primary breast lymphoma with skin involvement arising in lymphocytic lobulitis.
AB  - Primary breast lymphoma is a rare tumour which has recently been associated with
      pre-existing lymphocytic lobulitis. We report a patient with lymphocytic
      lobulitis in whom the lymphoma recurred in the contra-lateral breast 5 years
      after the initial presentation, to be followed shortly afterwards by skin
      involvement. This progression illustrates the relationship between extra-nodal
      lymphomas and underlying autoimmune disease and the homing of lymphomas to
      related sites.

PMID- 8144147
TI  - Glandular inclusions in fetal myocardium.

PMID- 8144148
TI  - Acute isolated amoebic appendicitis.

PMID- 8144149
TI  - Laterocervical lymphadenitis caused by Pneumocystis carinii in a patient with
      AIDS.

PMID- 8144150
TI  - Adenomyoepithelioma of the breast with features of malignancy.

PMID- 8144151
TI  - Lymphomas of Waldeyer's ring.

PMID- 8144152
TI  - "My most humorous moment in nursing".

PMID- 8144153
TI  - Welcome to the "real" nursing world.

PMID- 8144154
TI  - Tony Rutherford.

PMID- 8144155
TI  - Cultural diversity in the workplace.

PMID- 8144156
TI  - Shouldering the responsibility for culturally sensitive and competent health
      care.

PMID- 8144157
TI  - Priorities in health care reform.

PMID- 8144158
TI  - Learning the ropes.

PMID- 8144159
TI  - How nurses and nursing students can become politically active.

PMID- 8144160
TI  - Resources for political involvement.

PMID- 8144161
TI  - Shifting from high stress to high energy.

PMID- 8144162
TI  - Getting organized.

PMID- 8144163
TI  - Becoming a leader.

PMID- 8144164
TI  - 1993 publishers directory. Resource books for nursing students.

PMID- 8144165
TI  - Plug into the future--the power to care.

PMID- 8144166
TI  - A regulatory apparatus with DNA looping.

PMID- 8144167
TI  - Denatured supercoiled DNA--structural and biological activity.
AB  - Supercoiled DNA on treatment with NaOH followed by neutralization produces a
      condensed structure (form Id). This structure does not split into topoisomers
      when run on long gel in presence of intercalating agents and the migration of
      this form does not change appreciably in presence or absence of ethidium bromide.
      Relaxation of form Id by topoisomerase I from pea chloroplast is facilitated more
      than form I. Single-stranded binding (SSB) protein binds more to form Id as
      evidenced from gel retardation study. Hydroxyl radical nicking is facilitated in
      this form. Compared to form I, this form produces half the number of
      transformants, but adsorption and penetration remain almost same in both the
      forms. Post-transformational growth using 32P labelled form I and form Id showed
      greater amount of degradation in form Id.

PMID- 8144168
TI  - A type 1 DNA topoisomerase from the kinetoplast hemoflagellate Leishmania
      donovani.
AB  - A type 1 DNA topoisomerase has been purified from the nuclei of the kinetoplast
      hemoflagellate Leishmania donovani using polyethylene glycol fractionation and
      chromatography on hydroxylapatite, phosphocellulose and phenylsepharose column.
      The relaxation activity is ATP independent. Mg2+ is an essential cofactor for the
      reaction with an optimum at 10 mM. Mg2+ can be substituted by Mn2+ at 5 mM
      concentration. The relaxation reaction exhibits a salt optimum at 100 mM KCl. The
      enzyme can not remove supercoils from positive superhelical DNAs nor can induce
      supercoiling of relaxed DNAs. The topoisomerase activity is associated with a
      polypeptide of molecular weight about 67 kDa as shown by sephacryl-S200 gel
      filtration and by electrophoresis on sodium dodecyl sulphate-polyacrylamide gels.

PMID- 8144169
TI  - Inactivation of glyceraldehyde-3-phosphate dehydrogenase with SH-reagents and its
      relationship to the protein quaternary structure.
AB  - Inactivation of mung bean glyceraldehyde-3-phosphate dehydrogenase (GPDH) with
      excess iodoacetate or N-ethylmaleimide exhibits pseudo-first order kinetics at pH
      7.3 and 8.6 in the absence and presence of NAD+, suggesting that all the reactive
      SH groups (four per tetrameric GPDH molecule) have equivalent reactivity towards
      these reagents. This is similar to the D2-symmetry conformation proposed on the
      basis of thermal inactivation data [Malhotra and Srinivasan, Arch. Biochem.
      Biophys. 236, 775-781 (1985)]. With p-chloromercury benzoate (p-CMB), the
      inactivation of GPDH is very fast and its kinetics can be monitored at low
      reagent concentration only. Keeping a high molar p-CMB: enzyme ratio (= 47), the
      kinetics were found to be biphasic, with half of the activity being lost in a
      fast and the remaining in a slow phase, characteristic of C2-symmetry
      conformation and half site reactivity. The p-CMB inactivation could be largely
      reversed on the addition of excess cysteine. A comparison of these data with
      literature reports on this and other GPDHs reveals that all reagents having large
      non-polar moieties exhibit half site reactivity with this enzyme.

PMID- 8144170
TI  - Photosynthetic carbon reduction cycle metabolites and enzymes of sucrose and
      starch biosynthesis in developing Brassica pods.
AB  - Rate of net CO2 exchange and activities of the key enzymes of fru-2,6-P2, sucrose
      and starch synthesis and levels of certain intermediates of Calvin cycle were
      determined in Brassica pods at different stages of their development. The rate of
      net CO2 exchange, activities of FBPase, UDPG-pyrophosphorylase and SPS, and the
      contents of 3-PGA, DHAP, RuBP and UDPG increased up to day 21 after anthesis
      followed by a continuous decrease thereafter. However the content of fru-6-P
      started decreasing only after 28 days of anthesis. Changes in the levels of fru
      2,6-P2 were closely associated with the changes in F6P 2-kinase activity rather
      than with F2,6-P2ase activity. Similarly, activities of ADPG-pyrophosphorylase
      and ADPG-starch synthetase closely followed the pattern of starch accumulation in
      pod tissues. These observations suggest that during the early phase of pod
      development (up to 21 days after anthesis), which is also the active phase for
      pod photosynthesis, carbon is mainly utilised for sucrose synthesis and that
      during the later phase of pod development (from day 21 to 42 after anthesis),
      there is shift in metabolic path of carbon from sucrose to starch.

PMID- 8144171
TI  - Lipid peroxidation in hepatic microsomal membranes isolated from mice in health
      and in experimental leishmaniasis.
AB  - Normal hepatic microsomal membranes when exposed in vitro to different free
      radicals, cause membrane damage by lipid peroxidation which could be monitored by
      the analysis of malonaldehyde formation and measurement of membrane
      microviscosity. Lipid peroxidation in vivo, when examined in hepatic microsomal
      membranes in experimental Leishmaniasis, reveals a direct relationship between
      membrane microviscosity and the extent of lipid peroxidation. Scavengers of free
      radicals and peroxides such as superoxide dismutase (SOD) for O2.-, mannitol for
      (OH.) and catalase for H2O2 in modest amounts were used for preventing the
      membrane damage caused by lipid peroxidation.

PMID- 8144172
TI  - Enzyme electrode based on oxalate oxidase immobilized in gelatin for specific
      determination of oxalate.
AB  - A biosensor for the specific determination of oxalate was developed using oxalate
      oxidase (EC 1.2.3.4) from barley (Hordeum vulgare) seedling roots in combination
      with a dissolved oxygen probe. Oxalate oxidase immobilized with gelatin using
      glutaraldehyde and fixed on pretreated teflon membrane served as an enzyme
      electrode. The electrode response was maximum when 50 mM succinate buffer was
      used at pH 3.2 and 35 degrees C. The biosensor response depends linearly on
      oxalate concentration between 5 x 10(-6)-2 x 10(-4) M with response time 30 sec
      and substrate specificity of the oxalate oxidase electrode of 100%. The sensor is
      stable for more than 3 months during which time more than 400 assays can be
      performed.

PMID- 8144173
TI  - Studies on nonesterified fatty acids in rat intestinal cell membranes.
AB  - Lipid composition of total membrane fractions prepared from scraped rat
      intestinal mucosa and isolated epithelial cells were compared. Membranes prepared
      from mucosa had four times higher nonesterified fatty acids (NEFA) as compared to
      the epithelial cell membranes. Cholesterol and phospholipid contents were similar
      in both the membrane preparations but triglyceride content was high and di- and
      monoglyceride were low in epithelial cell membranes as compared to the mucosal
      membranes. Inclusion of p-bromophenacyl bromide, a phospholipase inhibitor, in
      the intestinal lumen wash solution and homogenizing buffer did not reduce the
      NEFA content of the scraped mucosal membranes whereas inclusion of diethyl p
      nitrophenyl phosphate, a lipase inhibitor reduced it by 40%. These results
      suggest that NEFA are normal constituent of intestinal cell membranes.

PMID- 8144174
TI  - Ascorbate-dependent formation of hydroxyl radicals in the presence of iron
      chelates.
AB  - The autoxidation of L-ascorbate on incubation in saline phosphate buffer (pH 7.4)
      is accompanied by hydroxyl radical (.OH) generation. The metal chelator EDTA
      showed significant inhibition of ascorbate autoxidation and ascorbate-dependent
      .OH release. On the other hand, Fe2+ (EDTA) greatly augmented both ascorbate
      autoxidation and ascorbate-dependent .OH production. The biological iron
      chelating compounds such as ATP, ADP, citrate and pyrophosphate suppressed both
      ascorbate autoxidation and ascorbate-mediated .OH production, thereby indicating
      that these compounds suppress the activating effect of iron. Ascorbate
      autoxidation and ascorbate-dependent .OH formation, stimulated by Fe2+ (EDTA)
      were significantly inhibited by .OH scavengers, namely mannitol, thiourea and
      sodium formate, as well as by catalase and to a lesser extent by bovine serum
      albumin, superoxide dismutase (native and heat denatured) and heat denatured
      catalase.

PMID- 8144175
TI  - Status of nitric oxide free radicals in diabetic neutrophils: effect of diabetic
      serum factor on the generation of these species in normal neutrophils and their
      relation to lysosomal degranulation.
AB  - Normal polymorphonuclear leukocytes (PMNL) in contrast to diabetic PMNL,
      generated significant amounts of .NO and NO2 when challenged with opsonised
      zymosan. Diabetic neutrophils, on the other hand, responded either weakly or
      insignificantly to the same stimulants. However, in resting state the levels of
      .NO and NO2 were higher in diabetic as compared to normal PMNL. Diabetic serum
      factor (DSF) provoked a significant generation of .NO and NO2 in normal PMNL, a
      phenomenon found parallel to the enhancement in cytosolic cathepsin D activity in
      normal cells on insult with DSF.

PMID- 8144176
TI  - Interaction of amino acids and gelatin with urea.
AB  - The pH titration of nine amino acids (glycine, proline, valine, serine,
      glutamine, tryptophan, arginine, histidine and aspartic acid) in presence of urea
      in the concentration range 1-8 mole dm-3 has been performed. The results support
      suppression of the first dissociation constant (K1) of the amino acids and
      acceptance of H+ ions by the amide forming uronium ion (UH+). The second
      dissociation constant (K2) of the amino acids is affected relatively weakly by
      urea. Quantitative evaluation of different species existing in solution and the
      degree of dissociation of the acids as well as the degree of binding of H+ ion to
      the amide have been made. It has been found that the polarity of the aqueous-urea
      medium does not straight forwardly correlate with the altered pK1 of the amino
      acids. Urea can also affect the pH-titration behaviour of gelatin with an
      increase of the intrinsic pK of the acidic groups of the protein by 0.45 unit.

PMID- 8144177
TI  - Analysis of biexponential nuclear magnetic resonance relaxation curves: studies
      on simulated data.
AB  - Application of a Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence to a nuclear
      spin system consisting of two components, whose spins do not exchange or exchange
      slowly on the scale of the shorter time constant, results in the nuclear
      magnetization Mz of the spin system decaying according to the relation Mz = Ma
      exp(-t/Ta)+Mb exp(-t/Tb)+K+E where Ma,Ta are the intensity and transverse
      relaxation time of one component, Mb and Tb are the corresponding values for the
      second component, K is a constant and E is the contribution due to noise. Data
      simulation according to the above function was carried out with different values
      for the parameters Ma, Ta, Mb, Tb and K, the noise component being normally
      distributed with mean zero. For each set of parameters, the data generation was
      repeated a number of times with a different noise content and in each case, the
      parameters were estimated using a non-linear least square curve fitting
      procedure. The mean and percent coefficient of variation (CV) of each parameter
      was calculated. The value of CV is taken as a measure of the uncertainty in the
      estimated value of the parameter. It is found that the uncertainty in the
      estimated values of the parameters is due to the random noise. The range of data
      points is more critical than the number of data points used in curve fitting.
      Moreover, the uncertainty associated with each parameter increases with
      decreasing Ma/Mb ratio and increases with increasing Ta/Tb ratio. Higher signal
      to noise ratios will be required to analyse data with low Ma/Mb and high Ta/Tb
      ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144178
TI  - Influence of cyclic AMP on the biosynthesis of phosphatidylcholine in Microsporum
      gypseum.
AB  - The influence of intracellular cAMP on phosphatidylcholine biosynthesis in
      Microsporum gypseum has been examined using radiolabelled precursors. The
      incorporation of labelled choline, methionine and ethanolamine into total lipids,
      phospholipids and choline containing phospholipids increased in aminophylline and
      decreased in atropine grown cells as a result of rise and fall in cAMP levels in
      these cells. The enhanced uptake of labelled methionine and ethanolamine in
      comparison to labelled choline in choline containing phospholipids in
      aminophylline grown cells suggests that methylation pathway is more influenced by
      cAMP than CDP-choline pathway.

PMID- 8144179
TI  - [Current perspectives in medical virology].

PMID- 8144180
TI  - [Current perspectives in molecular virology].
AB  - For reproduction viruses depend on the metabolism of higher organisms that use a
      variety of different antiviral mechanisms for defense. Insights into virus-host
      cell interactions and in the strategies viruses employ to produce progeny virions
      were possible by sophisticated methods of modern virology. Knowing about the
      molecular mechanisms during infection and replication we have been able to
      counteract viral attacks on the molecular level by rationally designed vaccines.
      On the other hand these viruses can be used as molecular vector tools for
      treatment of e.g. genetically determined diseases. On the basis of new molecular
      biological methods the sensitivity of detection of infectious agents and
      diagnosis of diseases could be drastically improved.

PMID- 8144181
TI  - [The importance of the polymerase chain reaction in the diagnosis of viral
      infections].
AB  - This review summarizes the basics of PCR technology. Besides technical details
      for optimization of the procedure, PCR as a diagnostic tool for viral infections
      is described. In the second part of the article, different techniques for the
      detection of the PCR products are described and compared.

PMID- 8144182
TI  - [New developments in antiviral chemotherapy].

PMID- 8144183
TI  - [Current perspectives in virology: prevention].
AB  - A short review of deficiencies in immune reactions in older adults resulting in
      an increase of vaccine-preventable diseases (e.g. influenza) in this age group is
      presented. Reasons for so-called vaccine failures (primary, secondary) in persons
      previously vaccinated against measles are discussed. The immune status against
      poliomyelitis of the population in Germany, based on repeated serosurveillance
      studies is presented, the immunity of persons previously TOPV-vaccinated against
      a poliovirus type 3 variant (Finland) is demonstrated.

PMID- 8144184
TI  - [What kinds of species are in the conjunctiva?].
AB  - With suitable culture methods less than 5% of conjunctival fluid specimens remain
      negative. From approximately 95% of the swab cultures at least 65 bacterial
      species - although in low numbers - were recovered. Among the predominant
      organisms were gram-positive species like several coagulase-negative
      Staphylococcus spp., Propionibacterium spp., Corynebacterium spp. and members of
      the genera Peptostreptococcus, Streptococcus and Actinomyces. Among the
      frequently isolated gram-negative species were members of the genera Neisseria
      and Haemophilus as well as Enterobacteriaceae like Proteus spp.

PMID- 8144185
TI  - [Immunologic isolation of transplanted islets of Langerhans: microcapsules with
      defined molecular limits].
AB  - Immunoisolated transplantation of islets of Langerhans in barium alginate
      microcapsules is a promising therapeutic approach to cure diabetes. An improved
      membrane for the coating of barium alginate microcapsules has been developed.
      Chemically stable barium alginate microcapsules with a controlled molecular
      weight cutoff between 9400 and 40,500 D were obtained after coating of barium
      alginate capsules in Polybrene solutions. Microcapsules prepared by this new
      method were still freely permeable to low molecular weight substances.

PMID- 8144186
TI  - The effect of bryostatin on protein kinase C-regulated functions in human T
      lymphocytes and epidermal keratinocytes.
AB  - The bryostatin (Bryo) is a macrocyclic lactone that binds specifically to protein
      kinase C (PKC) thereby affecting cell growth and differentiation and inhibits
      phorbol ester-induced tumor promotion. We used human peripheral blood lymphocytes
      (PBL) and epidermal cells in order to analyze the action mechanism of Bryo and
      compare it with that of the phorbol ester PMA. Bryo and PMA activated PBL- or T
      cell-derived PKC in a similar dose-response and induced a similar time kinetic of
      cytosol-to-membrane translocation of enzymatically active and immunoreactive PKC.
      In addition, the 2 drugs induced similar patterns of protein phosphorylation and
      activated the c-fos and c-jun genes that their protein products regulate
      transcription of TRE-containing genes. In contrast, long-term (20 h) treatment of
      cells with Bryo resulted in a marked loss of both cytosolic- and membrane-bound
      PKC while PMA induced only a slight reduction in the amount of cellular PKC.
      Inhibition of PMA-induced human T-cell proliferation by Bryo correlated with a
      reduction in the amount of cellular PKC. An opposite effect was observed in human
      epidermal cells where Bryo augmented growth and proliferation while PMA induced
      terminal differentiation and cell death. We propose that at least some of the
      differences in the biological effects induced by Bryo and PMA are due to distinct
      regulations of PKC. Thus, although both agents can initially bind to and activate
      PKC at a later time (approximately 16 h), Bryo, but not PMA, induces rapid PKC
      degradation and inhibition of PKC-regulated biological responses that are
      dependent on the continuous presence and/or activation of the enzyme.

PMID- 8144187
TI  - The effect of H-ras expression on tumorigenicity and immunogenicity of Balb/c 3T3
      fibroblasts.
AB  - In an attempt to define immunological parameters affected by the H-ras oncogene,
      we have used Balb/c 3T3 cells transfected with either H-ras (98/6), H-ras+v-myc
      (98/4v) or plasmid only (98/1). We found that while control and oncogene
      transfected Balb/c 3T3 cells exhibit similar low sensitivity to lysis by natural
      killer (NK) cells, H-ras+v-myc-transfected cells could immunize syngeneic Balb/c
      mice and induce cytotoxic T cells (CTL) with broad specificity, that lysed all
      types of Balb/c 3T3 cells tested. Immunization of Balb/c mice with 98/4v cells
      prevented homologous tumor formation and partially inhibited the formation of
      tumors derived from H-ras-transfected cells. 98/6 cells were not immunogenic in
      vivo and did not protect the animals from a challenge of 98/6 cells. The results
      suggested that CTLs but not NK effector cells were important for eliciting in
      vivo tumor rejection of H-ras+v-myc-transfected cells. In contrast, antigens
      eliciting the cytotoxic T-cell response, and possibly also the in vivo tumor cell
      rejection response, were expressed on all cell types tested but were immunogenic
      only on the surface of 98/4v cells. We further determined major
      histocompatibility complex (MHC) class-I molecule expression on the outer cell
      surface and found that H-2K was down-regulated in H-ras-transfected cells. The
      results support the observation that oncogenes can down-regulate specific MHC
      antigens, thereby preventing presentation of tumor antigens and allowing tumor
      escape from immune recognition.

PMID- 8144188
TI  - Epidermal Langerhans cells and HIV-1 infection.
AB  - Originating from the bone marrow, Langerhans cells migrate into the peripheral
      epithelia (skin, mucous membranes) and play a key role in the immune surveillance
      system against foreign antigens. They act as antigen-presenting cells through a
      specific cooperation with CD4+ lymphocytes after migration to the proximal lymph
      nodes. As HIV-1-permissive cells, Langerhans cells in genital or rectal mucosa
      may be the first infected cell type and may be the vectors of infection for CD4
      positive T cells. It has been clearly demonstrated that Langerhans cells may be
      infected in HIV-1 sero-positive patients. Recently in vitro experimental
      infection of Langerhans cells was achieved using a co-culture assay with HIV-1
      infected cells. Investigation into the exact role of Langerhans cells in the
      course of HIV-1 infection will contribute greatly to our understanding of AIDS
      pathogenesis.

PMID- 8144189
TI  - Early events in the experimental interstitial lung disease induced in sheep by
      the Visna-maedi virus.
AB  - Visna-maedi virus is a lentivirus closely related to the human immunodeficiency
      virus type I (HIV-I). During spontaneous infection of sheep by Visna-maedi virus
      an interstitial lung disease is observed. It is characterized by an alveolitis,
      peribronchovascular lymphoid nodules, alveolar wall thickening and myomatosis. In
      order to decipher the pathology of this lentiviral infection we have induced this
      disease in colostrum-deprived newborn lambs.

PMID- 8144190
TI  - Cytokine-induced tumor immunogenicity: endogenous interleukin-1 alpha expressed
      by fibrosarcoma cells confers reduced tumorigenicity.
AB  - A direct correlation between the constitutive expression of IL-1 alpha and
      reduced tumorigenicity of fibrosarcomas was observed. This was established in
      fibrosarcoma cell lines which produce IL-1 alpha 'spontaneously', possibly as an
      aberration of oncogene-mediated transformation or upon IL-1 alpha gene transfer.
      In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed,
      whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the
      mechanisms of tumor regression of the IL-1 alpha-positive fibroblastoid cell
      lines indicated that IL-1 alpha potentiates the development of tumor cell
      specific CTLs, which are of importance for tumor eradication. Thus, IL-1 alpha
      induces enhanced helper T cell activity which provides auxiliary signals for the
      growth/development of CTLs. Non-adaptive effector cells, activated locally by IL
      1 alpha-expressing fibrosarcoma cells, also contribute to the eradication of IL-1
      alpha-expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen
      presentation, by the malignant fibroblasts as well as by tissue-resident antigen
      presenting cells, thus further potentiating anti-tumor immune responses. Mice, in
      which IL-1 alpha-producing tumors were regressed, developed an immune memory and
      rejected a challenge with an IL-1 non-producing violent tumor cell line.
      Endogenous IL-1 alpha activates a cytokine cascade (i.e., IL-6, CSF), produced by
      the malignant cells and possibly also by stromal cells. However, IL-1 alpha
      expression is essential for fibrosarcoma eradication, while other cytokines
      possibly amplify and sustain its action.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144191
TI  - Skewed distribution of TCR V alpha 7-bearing T cells within tumor-infiltrating
      lymphocytes of HLA-A24(9)-positive patients with malignant glioma.
AB  - The identification and propagation of T cells with anti-tumor reactivity is
      critical for understanding the human immune response to tumors, which may
      possibly be useful in the successful implementation of adoptive immunotherapy
      against cancer. In order to address this question, we examined the diversity of
      mRNA transcripts of T-cell receptor (TCR) V alpha and V beta genes in tumor
      infiltrating lymphocytes (TIL) of 12 glioma specimens obtained at surgery. Using
      the polymerase chain reaction (PCR) method and primers for 18 different human TCR
      V alpha and 22 V beta families to analyze TCR V-(D)-J-C gene rearrangements, we
      detected a limited expression of TCR variable region, V alpha genes and
      predominant usage of V alpha 7 within glioma TIL. TCR V beta gene usage was more
      diverse than that for V alpha, but TCR V beta 13.1 was dominantly expressed in 9
      out of 12 patients. In addition, we analyzed the percentage of each V alpha- and
      V beta-bearing T-cell subpopulation in TIL as well as in peripheral blood
      lymphocytes (PBL) quantitatively. The distribution of T-cell subpopulation
      bearing each V alpha or V beta subfamily was variable and uneven in all cases. In
      3 cases, the distribution of V alpha 7-bearing T cells in TIL was far higher than
      in PBL. This phenomenon was not found in T cells bearing TCR V beta 13.1. We also
      performed human leukocyte antigen (HLA) typing in these patients, and A24(9) was
      observed in 8 out of 11 patients. Among them all 3 patients who showed a skewed
      distribution of V alpha 7-bearing T cells in TIL expressed HLA-A24(9). There was
      no correlation between particular class I or II type and TCR V beta gene usage.
      From these results, it was strongly suggested that T cells bearing TCR V alpha 7
      might be targeted to antigenic determinants on glioma cells, and such T-cell
      population may be useful as effector cells for cancer immunotherapy.

PMID- 8144192
TI  - Amphiphilic detergents inhibit production of IgG and IgM by human peripheral
      blood mononuclear cells.
AB  - All types (cationic, anionic and non-ionic) amphiphilic detergents significantly
      inhibited the production of both IgG and IgM by human peripheral blood
      mononuclear cells after polyclonal activation in vitro. The most potent
      inhibitors were didodecyldimethylammonium bromide (DDAB) and (1
      methyldodecyl)dimethylamine N-oxide (2-ATDNO). They were able to suppress
      effectively the immunoglobulin production in 10(-3)-10(-8) M concentrations. A
      medium inhibitory effect was observed with Slovapon, sodium dodecyl sulphate
      (SDS) and Triton X-100, while Slovanik showed an inhibition only in
      concentrations higher than 10(-2)%. These results suggest that amphiphilic
      detergents may be characterized as potential immunotoxic substances with very
      negative effects on the immunoglobulin production.

PMID- 8144193
TI  - Novel autoimmune phenomena induced in vivo by a new DNA binding protein Nuc: a
      study on MRL/n mice.
AB  - We previously purified a 55 kDa protein that preferentially expands anti-DNA
      antibody production both in vitro and in vivo across the H-2 barrier from culture
      supernatants of KML1-7 cells, cloned from a lupus-prone MRL/lpr mouse. By using
      the purified protein, termed nucleobindin (Nuc), we cloned cDNA and produced
      recombinant(r) Nuc in Escherichia coli. To elucidate the function of rNuc in
      vivo, we initially injected intraperitoneally 5 micrograms of rNuc without
      adjuvant into female MRL/n mice at 8 weeks of age and continued injection twice a
      week. As early as 5 weeks after administration, all mice treated showed an
      increase in IgG anti-double stranded (ds) DNA antibodies accompanied by IgG
      hypergammaglobulinemia (HG). Of particular interest was that these mice also
      produced anti-U1RNP antibodies and rheumatoid factor (RF) of IgG class, but not
      anti-Sm antibodies. Histopathologically, hypercellularity with occasional
      crescents in the glomeruli was observed, but evidence for lupus nephritis was
      lacking, indicating that some factors other than Nuc are necessary for the
      development of a lupus syndrome observed in MRL/lpr mice. Similar administration
      of lipopolysaccharide into MRL/n mice failed to induce autoantibodies except for
      a slight increase in serum IgG, suggesting that these autoimmune responses are
      not due simply to polyclonal B-cell activation. The presence of rNuc will give us
      a clue for further understanding of autoimmunity.

PMID- 8144194
TI  - Mechanisms of cellular cytotoxicity mediated by a recombinant antibody-IL2 fusion
      protein against human melanoma cells.
AB  - Functional characteristics were established for a genetically engineered fusion
      protein between human IL2 and mouse/human chimeric mAb 225 directed against human
      epidermal growth factor receptor (EGFR), aberrantly expressed on human melanoma
      cells. The emphasis of these studies was on the mechanism(s) of action by which
      the ch225-IL2 fusion protein mediated cytotoxic killing of human melanoma cells
      by different human immune effector cells. Ch225-IL2 fusion protein bound to human
      EGFR with the high affinity of the parental antibody, and was as active as the
      equivalent amount of rhIL2. Ch225-IL2 enhanced cellular cytotoxicity mediated by
      freshly separated PBMC, isolated natural killer (NK) cells and activated T cells
      against melanoma cell lines. NK cells, which constitutively express both Fc gamma
      RIII and IL2R, interacted with ch225-IL2, mainly through Fc gamma RIII, while the
      involvement of IL2R was secondary. However, the effect of ch225-IL2 on activated
      T cells was most likely mediated through IL2R. These results suggest that the
      genetically engineered ch225-IL2 fusion protein may become a potent
      immunotherapeutic agent capable of stimulating various immune effector
      populations to effectively kill human melanoma cells.

PMID- 8144195
TI  - Serum IgA and IgG subclasses during treatment for acute respiratory exacerbation
      in cystic fibrosis: analysis of patients colonised with mucoid or non-mucoid
      strains of pseudomonas aeruginosa.
AB  - Patients with cystic fibrosis (CF) have a high prevalence of Pseudomonas
      aeruginosa infection which causes chronic infection of the mucosal surfaces of
      the lung. This results in recurrent immune stimulation and
      hypergammaglobulinemia. The present study examines the levels of circulating Ig
      classes, IgG and IgA subclasses in 13 adult patients with CF during acute
      pulmonary infection and post-exacerbation. Total serum IgG levels were raised in
      the patients during infection and post-treatment when compared to the normal
      range (mean +/- SEM: 17.21 +/- 1.4 g/l vs 16.45 +/- 1.5 g/l respectively; normal
      range 8-16 g/l). In contrast, total IgM (2.6 +/- 0.26 vs 2.69 +/- 2.74 g/l;
      normal range 0.6-2.8 g/l) and IgA levels (2.5 +/- 0.52 vs 2.41 +/- 0.48 g/l;
      normal range 0.5-4 g/l) remained unchanged when examined during all stages of the
      disease. Of the 13 patients studied, 69%, 39% and 31% had IgG, IgM and IgA levels
      respectively raised above the normal range values. The mean levels of individual
      IgG subclasses examined in this group of patients revealed values within the
      normal ranges, however IgG2 and IgG3 were increased in 31% and 46% of patients.
      Individual IgG3 levels fell in 77% (10/13) and IgG4 in 62% (8/13) of the patients
      post-exacerbation. With regard to IgA subclasses, significant reduction in the
      IgA1 levels were observed post treatment (3687 +/- 539 mg/l vs 2713 +/- 498 mg/l,
      p < 0.01). In contrast, IgA2 levels were increased from 279 +/- 49 mg/l to 421 +/
      69 mg/l, although statistical significance was not reached. Upon antibiotic
      treatment for infection, the findings in this study show that IgA1 which is
      susceptible to bacterial proteases is reduced with a concommitant increase in the
      protease resistant IgA2 subclass. Moreover, patients colonised with non-mucoid
      strains of P. aeroginosa had higher total IgA levels due to the raised IgA1
      subclass whereas they had lower IgG levels due to low IgG2 and IgG4 subclasses.

PMID- 8144196
TI  - Effect of anti-human sperm monoclonal antibodies on mouse in vitro fertilization.
AB  - We employed anti-human sperm monoclonal antibodies to investigate how sperm
      membrane antigens are involved in gamete interactions. We have produced seven
      monoclonal antibodies specific for human sperm antigens, that showed reaction
      with mouse sperm by ELISA and by immunofluorescence. These antibodies did not
      react with zona pellucida or any other somatic human tissue. Some degree of
      toxicity was detected for oocytes at high antibody concentration and this was
      correlated with their inhibitory effect on fertilization. Unrelated to the degree
      of antigen expression or localization on sperm membrane, the antibodies showed
      several degrees of inhibition. The participation in sperm-zona pellucida
      interaction for every antigen could be evidenced by the impaired penetration of
      sperm caused by the presence of several concentrations of antibody. Thus, DAN-2,
      MOU-8 and VAC-4 inhibit mouse in vitro fertilization.

PMID- 8144197
TI  - Expression of a recombinant sheep IgE gene.
AB  - An ovine cosmid library was screened with a bovine C epsilon gene probe. IgE and
      IgA constant region genes (C epsilon and C alpha, respectively) were isolated
      within a single 26 kb cosmid insert. The C epsilon gene was cloned into an
      expression vector which contained the rearranged VDJ genomic segment encoding an
      anti-(4-hydroxy-3-iodo-5-nitrophenyl) acetic acid (anti-NIP) VH chain. This
      chimeric construct was transfected into murine hybridoma cells producing L chain
      with anti-NIP antibody specificity and stable transfectomas secreting chimeric
      ovine-murine IgE anti-NIP antibodies were obtained. Chimeric antibody, affinity
      purified from culture supernatants of transfected cells on a NIP-sepharose
      column, was characterised by SDS-PAGE and shown to contain H and L chains of
      expected size. These experiments demonstrated the power of advanced molecular
      genetic techniques to generate immunological reagents against low abundance
      immunoglobulin isotypes thus facilitating monoclonal antibody production for
      further immunological studies.

PMID- 8144198
TI  - Complement dependent cytotoxicity of sensory ganglion neurons mediated by the
      gp120 glycoprotein of HIV-1.
AB  - Patients infected with HIV-1 frequently have a sensory neuropathy, but the cause
      is unknown. We found that the gp120 glycoprotein of HIV-1 bound to the surface of
      cultured rat dorsal root ganglia (DRG) neurons, and activated the complement
      cascade to lyse the neuronal cells. Cytotoxicity was measured by a 51Cr-release
      assay, and deposits of the C5b-9 complement complex were detected on the affected
      cells. As controls, gp120 or complement alone, or rgp120 plus deactivated
      complement, did not damage the neuronal cells, and fibroblasts were unaffected.
      The gp120 glycoprotein can thereby damage DRG neurons by complement dependent
      mechanisms. This interaction may contribute to the development of the sensory
      neuropathy in AIDS.

PMID- 8144199
TI  - HIV testing policies--an overview.

PMID- 8144200
TI  - Proposed national HIV testing policy.

PMID- 8144201
TI  - The management of HIV infection in India.

PMID- 8144202
TI  - Prevalence of HIV infection in pregnant women in Vellore region.
AB  - All pregnant women attending the antenatal clinic of a large hospital in Vellore,
      India (Christian Medical College Hospital) were screened for HIV infection
      between October 1987 and June 1992. A total of 36,953 blood samples were thus
      screened and 20 infected women were identified. Among these 18 women had acquired
      HIV infection from their husbands, who were also detected to be HIV infected.
      While these 18 women were monogamous, all the husbands had multiple sex partners.
      Two of the 20 women in this series were commercial sex workers. Among the 20, 17
      (85%) women belonged to low socio-economic status, while three were from well-to
      do families, with the husbands being businessmen or teachers. As the overall
      prevalence (0.054%) of HIV infection among pregnant women was relatively high and
      equal to or higher than many States in the USA and in areas outside London in the
      UK, the authors recommend that strict universal precautions be instituted in all
      obstetric practice in India.

PMID- 8144203
TI  - HIV screening & risk behaviour in psychoactive substance users.
AB  - Patients admitted to the Drug De-addiction and Treatment Centre, Postgraduate
      Institute of Medical Education & Research, Chandigarh, were screened for HIV
      antibodies. Out of 116 patients, 45 (39%) were injecting drug users (IDUs), 29
      (25%) were other drug users and 42 (36%) were primary users of alcohol. One IDU
      was HIV seropositive (2.2% of the IDUs). Analysis of HIV-related risk behaviour
      showed that the IDUs were at high risk, because of needle sharing as also because
      of having multiple sex partners. The potential for HIV infection in these persons
      practising high-risk behaviour calls for timely preventive measures.

PMID- 8144204
TI  - Estimation of immunisation coverages in children by WHO 30-cluster survey.
AB  - A WHO 30-cluster survey for estimating immunisation coverages in infancy was
      undertaken in each of 5 districts in Tamil Nadu, strictly according to the
      specifications laid out in the WHO manual. The main aim was to examine whether
      the technique would provide estimates with the required degree of precision under
      Indian conditions. Of 60 sample survey estimates, 57 had the targeted degree of
      precision (i.e., 95% confidence limits of +/- 10 percentage points), which is in
      excellent agreement with expectation. The proportions of infants on whom
      immunisation was initiated, were very high for DPT vaccine (88-99%) and polio
      vaccine (85-99%); however, of those who had received the first dose, 23-39 per
      cent did not complete the 3-dose schedule. Estimated coverage with measles
      vaccine ranged from 15 to 54 per cent, while BCG coverage ranged from 53 to 97
      per cent. Better health education regarding the need and correct age for
      immunisation, and more effective motivation at the time of administration of the
      first dose of DPT/polio vaccine, are recommended.

PMID- 8144205
TI  - Resistance of shigella to nalidixic acid & fluorinated quinolones.
AB  - It is known that nalidixic acid resistance is a relatively rare phenomenon among
      shigellae. Between June 1989 and May 1990, six strains of shigellae resistant to
      nalidixic acid were isolated. These strains also exhibited resistance to three
      newer fluoroquinolones, viz., ciprofloxacin, pefloxacin and enoxacin. In repeated
      experiments, nalidixic acid resistance did not transfer to a suitable recipient.

PMID- 8144206
TI  - Evaluation of enzyme-linked immunosorbent assay in the diagnosis of kala-azar in
      Malda district (West Bengal).
AB  - An immunological test based on indirect (plate) ELISA has been successfully
      standardized and modified using promastigote soluble antigen. The test carried
      out on 813 subjects from a kala-azar endemic area (including parasitologically
      confirmed patients, subjects presenting with clinical symptoms of visceral
      leishmaniasis and endemic controls) and a non-endemic area (with diseases other
      than kala-azar and apparently normal subjects) was found to detect, specifically,
      antileishmanial antibodies. The plate ELISA has been simplified to a more
      sensitive dot-ELISA where the results are read within 2-3 h. The antigen
      requirement is 250 ng per test. No cross-reactivity with sera from patients of
      malaria, tuberculosis, leprosy, amoebiasis and filariasis was observed. The
      follow up monitoring of antibodies in successfully treated kala-azar patients
      showed a decline of antibodies. A drop of blood taken on filter paper is
      sufficient to conduct the test. Dot ELISA therefore is a simple, inexpensive and
      stable test in serodiagnosis of visceral leishmaniasis.

PMID- 8144207
TI  - paragonimiasis in Manipur.
AB  - A survey was undertaken in the east district of Imphal valley of Manipur, India,
      using an intradermal test with saline extract of adult Paragonimus westermani as
      test antigen to find out the prevalence of paragonimiasis and some of the
      epidemiological factors attributable to it. A total of 3,467 individuals of both
      sexes aged five years and above were tested. A total of 2934 persons admitted
      eating crabs and among them 234 were found reactive to Paragonimus antigen. The
      prevalence rate observed was 6.7 per cent. The proportion of positive reactors
      (8.0%) among the crab eaters compared to 0.1 per cent among those who did not eat
      crabs was highly significant (P < 0.01). The difference in the prevalence rates
      in different age groups and different sexes was also found to be highly
      significant. The habit of eating raw and or undercooked crabs had significant
      correlation with skin reactivity. The intradermal test was found to be a good
      screening test for mass surveys due to its simplicity, low cost, high sensitivity
      and no known untoward reaction. Four persons among the skin positive reactors
      presented with cough, pain in the chest, recurrent haemoptysis as major clinical
      manifestations. Laboratory investigations revealed Paragonimus eggs in the sputum
      smears, raised erythrocyte sedimentation rate, and high absolute eosinophil count
      in their blood. Praziquantel, the drug of choice was given at a dose of 25 mg per
      kg body weight 3 times a day for three consecutive days to each patient for a
      cure.

PMID- 8144208
TI  - Angiotensin-converting enzyme inhibition improves cardiac function. Role of
      bradykinin.
AB  - The effect of chronic low- and high-dose treatment with the angiotensin
      converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day) on the
      development of hypertension and left ventricular hypertrophy as well as on
      functional and biochemical alterations of the heart was studied in stroke-prone
      spontaneously hypertensive rats treated prenatally and subsequently up to the age
      of 20 weeks. The contribution of endogenous bradykinin potentiation to the ACE
      inhibitor actions was assessed by cotreatment of rats with the bradykinin B2
      receptor antagonist Hoe 140 (500 micrograms/kg per day SC) from 6 to 20 weeks of
      age. High- but not low-dose ACE inhibitor treatment prevented the development of
      hypertension and left ventricular hypertrophy. Chronic bradykinin receptor
      blockade did not attenuate the antihypertensive and antihypertrophic actions of
      ramipril. High-dose ramipril treatment improved cardiac function, as demonstrated
      by an increase in left ventricular pressure (29.9%), dP/dtmax (34.9%), and
      coronary flow (22.1%), without a change in heart rate. The activities of lactate
      dehydrogenase and creatine kinase and lactate concentration in the coronary
      effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively. Myocardial tissue
      concentrations of glycogen and the energy-rich phosphates ATP and creatine
      phosphate were increased by 31.3%, 39.9%, and 73.7%, respectively, whereas
      lactate was decreased by 20.8%. Chronic low-dose ACE inhibitor treatment led to a
      pattern of changes in cardiodynamics and cardiac metabolism similar to that
      observed with the high dose. All ACE inhibitor-induced effects on cardiac
      function and metabolism were abolished by chronic bradykinin receptor
      blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144209
TI  - Increases in cardiac kinins as a new mechanism to protect the heart.

PMID- 8144210
TI  - Hypertension in the transgenic rat TGR(mRen-2)27 may be due to enhanced kinetics
      of the reaction between mouse renin and rat angiotensinogen.
AB  - The transgenic rat TGR(mRen-2)27, in which the Ren-2 mouse renin gene is
      transfected into the genome of the rat, develops severe hypertension with high
      adrenal renin and low kidney renin. These animals express both mouse and rat
      renin. To investigate the cause of hypertension in the TGR rat, we compared the
      kinetics of mouse renin acting on mouse and rat angiotensinogens. The optimum pH
      of the renin reaction in the Sprague-Dawley rat was 6.5, whereas the optimum pH
      of the reaction in the TGR rat was approximately 8.5. The optimum pH of the renin
      reaction in the DBA mouse was 6.0. Purified mouse Ren-2 renin acting on rat
      angiotensinogen showed a pH profile similar to that for the renin reaction in the
      TGR rat. The angiotensinogen concentration in pooled plasma from eight DBA mice
      was 104.5 ng angiotensin I/mL and was clearly lower than that in Sprague-Dawley
      rats (772.4 +/- 37.3 ng angiotensin I/mL, n = 4). The reaction of purified mouse
      Ren-2 renin with rat angiotensinogen was 10 times faster than with mouse
      angiotensinogen. Plasma renin activity in DBA mice increased dramatically on
      addition of rat angiotensinogen (from 253.4 +/- 66.7 to 225,000 +/- 48,000 ng
      angiotensin I/mL per hour). Intravenous injection of 2 or 10 microL of DBA mouse
      plasma into the nephrectomized Sprague-Dawley rat increased the mean arterial
      pressure of the rat by 27.7 +/- 4.7 and 61.8 +/- 2.7 mmHg, respectively, whereas
      injection of 200 microL of Sprague-Dawley rat plasma did not change the mean
      arterial pressure of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144211
TI  - Transgenes, hypotheses, and hypertension.

PMID- 8144212
TI  - Regional differences in mortality during 15-year follow-up of 11,936 hypertensive
      veterans.
AB  - Several different investigators have reported increased stroke mortality in the
      southeastern United States, leading to the introduction of the term "Stroke
      Belt." The results presented here from the Veterans Administration Hypertension
      Screening and Treatment Program (HSTP) demonstrate an increased all-cause
      mortality among hypertensive patients seen in HSTP clinics in the southeastern
      United States when compared with similar patients from other HSTP clinics.
      Several different groupings of southeastern states were examined and compared
      with nine states west of the Mississippi River. A total of 11,936 male veterans,
      5737 of whom were black, were identified as hypertensive during 1974-1976 in 32
      HSTP clinics. Their mean age was 52.4 +/- 10.4 years, and their mean pretreatment
      blood pressure was 153.8 +/- 19.1/100.4 +/- 9.8 mm Hg. During a minimum of 13.9
      years of follow-up, 5360 (44.9%) of these patients died. Proportional hazards
      modeling was used to fit a basic survival model with terms representing race,
      age, blood pressure, smoking, and obesity. Risk was increased with higher blood
      pressure, age, and smoking and with lower body mass index. For 6 HSTP clinics in
      an 11-state Stroke Belt (defined as states with stroke mortality > 10% above the
      United States average), the relative risk of death was 1.226 (95% confidence
      interval, 1.106-1.358) when compared with 9 states west of the Mississippi River.
      For two different groupings of southeastern states with 10 and 8 HSTP clinics the
      relative risk of death was 1.231 and 1.295.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144213
TI  - Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides.
AB  - We examined the dose-related effects of angiotensin-converting enzyme inhibitors
      on circulating and tissue levels of angiotensin and bradykinin peptides by
      administering perindopril or lisinopril to rats in drinking water for 7 days. A
      reduction in the ratio of plasma angiotensin II (Ang II) to Ang I was seen for
      0.006 mg/kg per day perindopril, with an increase in plasma renin and Ang I at
      0.017 mg/kg per day. Plasma Ang II levels did not decrease until 1.4 mg/kg per
      day perindopril, at which dose plasma Ang I levels reached a plateau of an
      approximate 25-fold increase. The effects of perindopril on Ang II and Ang I
      levels in heart, lung, aorta, and brown adipose tissue were parallel to those
      observed for plasma. By contrast, renal Ang I levels did not increase, and renal
      Ang II levels decreased by 40% at 0.017 mg/kg per day, the same threshold seen
      for the increase in plasma renin. Perindopril increased circulating bradykinin-(1
      9) levels approximately eightfold, with a threshold dose of 0.052 mg/kg per day,
      and increased bradykinin-(1-9) levels in kidney, heart, and lung in parallel with
      the changes observed for plasma. By contrast, aortic and brown adipose tissue
      bradykinin-(1-9) and bradykinin-(1-7) levels increased severalfold for
      perindopril doses as low as 0.006 mg/kg per day. Lisinopril also increased aortic
      bradykinin-(1-9) and bradykinin-(1-7) levels at doses below the threshold for the
      decrease in the ratio of Ang II to Ang I. These data indicate that renal Ang II
      levels and vascular bradykinin-(1-9) levels respond to low doses of converting
      enzyme inhibitor and may be important mediators of the effects of these
      compounds. The parallel increases in bradykinin-(1-9) and bradykinin-(1-7) levels
      in aorta and brown adipose tissue, at inhibitor doses below the threshold for
      inhibition of Ang I conversion, may result from a mechanism different from
      inhibition of "classic" angiotensin-converting enzyme.

PMID- 8144214
TI  - Kinins contribute to the improvement of insulin sensitivity during treatment with
      angiotensin converting enzyme inhibitor.
AB  - Although angiotensin converting enzyme inhibitors and alpha 1-blockers have been
      reported to improve insulin sensitivity, their mechanisms of action have not been
      elucidated. To investigate the role of kinins in insulin sensitivity, we treated
      4-week-old spontaneously hypertensive rats with either an angiotensin converting
      enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin
      II antagonist (losartan) for 3 weeks. A control group received no drugs. In
      addition, 18 rats treated with enalapril or doxazosin received a simultaneous
      administration of a kinin antagonist (Hoe 140). Glucose clamp testing was
      performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2
      mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg)
      (P < .01). The glucose requirement for the clamp test during the administration
      of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per
      minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute)
      (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin
      (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9
      mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure
      induced by enalapril. In addition, losartan decreased mean blood pressure but did
      not affect the glucose requirement. Thus, the improvement in insulin sensitivity
      produced by an angiotensin converting enzyme inhibitor is mostly dependent on
      kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves
      insulin sensitivity irrespective of kinins.

PMID- 8144215
TI  - High-fructose feeding elicits insulin resistance, hyperinsulinism, and
      hypertension in normal mongrel dogs.
AB  - To determine whether chronic high-fructose feeding causes insulin resistance and
      hypertension in normal dogs, we fed 10 male dogs a normosodic diet containing 60%
      of the calories as fructose for 20 to 28 days; a control group of 8 dogs was fed
      a similar diet containing dextrose instead of fructose. In the fructose-fed
      group, (1) fasting triglyceridemia increased from 35.3 +/- 0.63 to 91.9 +/- 11.55
      mg/dL after 25 days (P < .001); (2) fasting insulinemia increased from 19.0 +/-
      1.9 to 58.9 +/- 7.22 microU/mL after 25 days (P < .001); (3) insulin resistance,
      which was estimated by steady-state glycemia during an insulin suppression test,
      increased from 105.8 +/- 21.5 to 187.8 +/- 32.6 mg/dL after 15 days (P < .001),
      whereas steady-state insulinemia did not change; (4) mean arterial pressure
      increased from 100.4 +/- 1.6 to 122.6 +/- 2.3 mm Hg after 28 days (P < .01); and
      (5) cumulative sodium balance was increased on days 7 through 11 (111.60 +/- 4.44
      mEq on day 8, P < .01), returning to normal for the rest of the experiment. All
      these parameters were similar between the fructose-fed and dextrose-fed groups
      before the diets were started and remained constant in the dextrose-fed group.
      Neither group showed any change in body weight, fasting plasma glucose, atrial
      natriuretic factor, or endothelin-1 levels. We conclude that chronic high
      fructose feeding elicits hypertriglyceridemia, insulin resistance,
      hyperinsulinemia, hypertension, and a transient sodium retention in dogs without
      fostering fasting hyperglycemia or weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144216
TI  - Quantification of retinal capillary density and flow velocity in patients with
      essential hypertension.
AB  - Arterial hypertension is known to be an important risk factor for cerebral and
      cardiovascular disease. Previous studies in rats have demonstrated that changes
      in both capillary density and vessel diameter may contribute to increased
      vascular resistance in hypertension. In vivo studies of human subjects with
      essential hypertension revealed a reduction in the number of arterioles in the
      skin and conjunctiva; no other in vivo data are available from other tissues. By
      means of a new imaging technique, capillary density and capillary blood flow
      velocity can now be assessed in the human retina. We undertook the present
      investigation to determine whether patients with essential hypertension and only
      minor clinical retinal vascular alterations have decreased retinal capillary
      density and altered capillary flow velocity. Seventeen hypertensive patients with
      only minor retinal vascular alterations and 17 healthy volunteers matched for age
      were selected. All study participants underwent ophthalmologic examination and
      fluorescein angiographic studies by means of scanning laser ophthalmoscopy.
      Capillary density and capillary blood flow velocity in the perifoveal network
      were evaluated from the angiograms. The retinal microcirculation in the
      perifoveal capillary network of hypertensive patients showed significant
      alterations. Both the capillary density and capillary flow velocities were
      significantly reduced compared with the control group. For the first time
      alterations of capillary blood flow and capillary density in a vascular network
      very similar to that of the brain have been demonstrated in hypertensive patients
      in vivo. Further studies with this technique may help identify patients at high
      risk for cerebrovascular diseases.

PMID- 8144217
TI  - Effect of potassium on vasodilation to acetylcholine in essential hypertension.
AB  - Patients with essential hypertension show impaired endothelium-dependent
      vasodilation induced by acetylcholine. Because dietary potassium supplementation
      increases endothelium-dependent relaxations to acetylcholine in hypertensive
      rats, we designed the present study to investigate whether potassium increases
      endothelium-dependent vasodilation in essential hypertensive patients. Therefore,
      in patients with essential hypertension (n = 13) and in normotensive control
      subjects (n = 13) we evaluated the effect of intrabrachial potassium chloride
      (0.2 mmol/min) on forearm blood flow (strain-gauge plethysmography) modifications
      induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15
      micrograms/100 mL forearm tissue per minute). In both groups of patients,
      potassium chloride infusion augmented local plasma potassium concentrations.
      Furthermore, in essential hypertensive patients but not in normotensive subjects
      it increased the vasodilating effect of the first three infusion rates of
      acetylcholine. In contrast, in seven adjunctive essential hypertensive patients,
      potassium chloride did not alter intrabrachial sodium nitroprusside-induced
      forearm vasodilation (1, 2, and 4 micrograms/100 mL forearm tissue per minute).
      Finally, to evaluate the role of nitric oxide on potassium-dependent facilitation
      of acetylcholine-induced vasodilation in essential hypertension, we studied the
      effect of intrabrachial NG-monomethyl L-arginine (100 micrograms/100 mL per
      minute) in another group of seven hypertensive patients. Vasodilation to
      acetylcholine was again increased by potassium chloride; NG-monomethyl L-arginine
      slightly blunted the vasorelaxing effect of acetylcholine but abolished the
      potentiating effect of potassium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144218
TI  - Baroreflex failure in a patient with central nervous system lesions involving the
      nucleus tractus solitarii.
AB  - Animal studies have shown the importance of the nucleus tractus solitarii, a
      collection of neurons in the brain stem, in the acute regulation of blood
      pressure. Impulses arising from the carotid and aortic baroreceptors converge in
      this center, where the first synapse of the baroreflex is located. Stimulation of
      the nucleus tractus solitarii provides an inhibitory signal to other brain stem
      structures, particularly the rostral ventrolateral medulla, resulting in a
      reduction in sympathetic outflow and a decrease in blood pressure. Conversely,
      experimental lesions of the nucleus tractus solitarii lead to loss of baroreflex
      control of blood pressure, sympathetic activation, and severe hypertension in
      animals. In humans, baroreflex failure due to deafferentation of baroreceptors
      has been previously reported and is characterized by episodes of severe
      hypertension and tachycardia. We present a patient with an undetermined process
      of the central nervous system characterized pathologically by ubiquitous
      infarctions that were particularly prominent in the nucleus tractus solitarii
      bilaterally but spared the rostral ventrolateral medulla. Absence of a
      functioning baroreflex was evidenced by the lack of reflex tachycardia to the
      hypotensive effects of sodium nitroprusside, exaggerated pressor responses to
      handgrip and cold pressor test, and exaggerated depressor responses to meals and
      centrally acting alpha 2-agonists. This clinicopathological correlate suggests
      that the patient's baroreflex failure can be explained by the unique combination
      of the destruction of sympathetic inhibitory centers (ie, the nucleus tractus
      solitarii) and preservation of centers that exert a positive modulation on
      sympathetic tone (ie, the rostral ventrolateral medulla).

PMID- 8144219
TI  - Renal sodium handling in patients with untreated hypertension and white coat
      hypertension.
AB  - Renal tubular sodium handling was investigated prospectively in 48 normotensive
      subjects, 53 untreated hypertensive patients, and 13 patients with white coat
      hypertension using endogenous trace lithium as a marker of proximal sodium
      reabsorption. A 12-hour daytime ambulatory blood pressure recording was performed
      in all patients to confirm the diagnosis of hypertension. Patients were included
      in the white coat hypertension group if their office blood pressure was above
      160/90 mm Hg but the mean value of their 12-hour ambulatory recording was lower
      than 140/90 mm Hg. All participants were studied on their normal diet and ate
      salt freely. Fractional excretions of sodium (FENa), lithium (FELi), and
      potassium (FEK) were measured simultaneously before blood pressure recording.
      FENa was significantly higher in hypertensive patients (0.84 +/- 0.05%, P < .05)
      than in normotensive control subjects (0.60 +/- 0.06%), and FELi was comparable
      in the two groups (15.4 +/- 0.65% in hypertensive patients and 17.0 +/- 0.9% in
      control subjects). However, the relation between FENa and FELi was significantly
      different in normotensive subjects and hypertensive patients (P < .001), so that
      for a given increase in FENa a smaller increase in FELi was observed in
      hypertensive patients. In addition, the ratios of urinary lithium to sodium and
      urinary potassium to sodium were significantly reduced in hypertensive patients,
      suggesting an increased proximal reabsorption of sodium. Similar alterations in
      renal tubular sodium handling were observed in patients with white coat
      hypertension. These results suggest that an increased sodium reabsorption in the
      proximal tubule may contribute to the maintenance of hypertension and that white
      coat hypertension might represent a prehypertensive state.

PMID- 8144220
TI  - Regulation of intracellular pH in the spontaneously hypertensive rat. Role of
      bicarbonate-dependent transporters.
AB  - Previous studies that have evaluated the Na(+)-H+ antiporter in cells from
      hypertensive subjects were generally performed under conditions in which HCO3
      CO2, the physiological buffer system, was absent from the assay media. The
      objective of this study was to evaluate the activity of the Na(+)-H+ antiporter
      and that of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchangers in
      cells assayed in the presence of HCO3-CO2 in the media. Lymphocytes from 6- to 8
      week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY)
      rats were obtained from the thymus gland and assayed immediately after isolation.
      The activity of the Na(+)-H+ antiporter after stimulation by cell acidification
      (pHi approximately 6.4) was similar in SHR and WKY rats (18.67 +/- 1.03 and 16.12
      +/- 0.92 mmol H+/L per minute, respectively). Recovery from cell alkalinization
      was effected by an Na(+)-independent Cl(-)-HCO3- exchanger, with maximal activity
      at an alkaline pHi (approximately 7.7). The stimulated activity of this Na(+)
      independent Cl(-)-HCO3- exchanger was also not different between SHR and WKY
      cells (2.65 +/- 0.25 and 2.55 +/- 0.32 mmol H+/L per minute, respectively). Acute
      chloride removal produced a rise in pHi that was Na(+)-dependent and sensitive to
      4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) but resistant to
      ethylisopropylamiloride (EIPA), reflecting the activity of an Na(+)-dependent Cl(
      )-HCO3- exchanger. Unlike the Na(+)-H+ exchanger and the Na(+)-independent Cl(-)
      HCO3- exchanger, which had their highest activities at extremes of pHi (low pHi,
      Na(+)-H+ exchanger, and high pHi, Na(+)-independent Cl(-)-HCO3- exchanger), the
      Na(+)-dependent Cl(-)-HCO3- exchanger had its maximal activity near steady-state
      pHi (approximately 7.1). No significant differences were found in the stimulated
      activity of this exchanger between cells from SHR and WKY rats (2.23 +/- 0.26 and
      2.50 +/- 0.43 mmol H+/L per minute, respectively). The kinetic properties of the
      Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchanger, examined as a
      function of external Cl-, were also virtually identical in cells from SHR and WKY
      rats. We conclude that in lymphocytes from SHR and WKY rats, the activity of the
      two Cl(-)-HCO3- exchangers, like that of the Na(+)-H+ exchanger, is dependent on
      the prevailing pHi. The Na(+)-dependent Cl(-)-HCO3- exchanger has its highest
      activity near steady-state pHi, suggesting an important role in the cell defense
      against intracellular acidosis under physiological conditions.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8144221
TI  - Dietary calcium and blood pressure in experimental models of hypertension. A
      review.
AB  - More than 80 studies have reported lowered blood pressure after dietary calcium
      enrichment in experimental models of hypertension. The evidence presented here
      suggests that dietary calcium may act concurrently through a number of
      physiological mechanisms to influence blood pressure. The importance of any given
      mechanism may vary depending on the experimental model under consideration.
      Supplemental dietary calcium is associated with reduced membrane permeability,
      increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These
      results suggest that supplemental calcium may limit calcium influx into the cell
      and improve the ability of the VSMC to extrude calcium. This could be a direct
      effect of calcium on the VSMC or an indirect effect mediated hormonally. The
      calcium-regulating hormones have all been found to have vasoactive properties and
      therefore may influence blood pressure. Furthermore, CGRP and the proposed
      parathyroid hypertensive factor are both vasoactive substances that are
      responsive to dietary calcium. Therefore, diet-induced variations in calcium
      regulating hormones may influence blood pressure. Modulation of the sympathetic
      nervous system is another important way that dietary calcium can influence blood
      pressure. There is evidence of altered norepinephrine levels in the hypothalamus
      as a consequence of manipulations of dietary calcium as well as changes in
      central sympathetic nervous system outflow. Dietary calcium has also been shown
      to specifically modify alpha 1-adrenergic receptor activity in the periphery. In
      some experimental models of hypertension, dietary calcium may alter blood
      pressure by changing the metabolism of other electrolytes. For example, the
      ability of calcium to prevent sodium chloride-induced elevations in blood
      pressure may be attributed to natriuresis. However, natriuresis does not account
      for all of the interactive effects of calcium and sodium chloride on blood
      pressure. Sodium chloride-induced hypertension may be due in part to calcium
      wasting and subsequent elevation of calcium-regulating hormones. Chloride is an
      important mediator of this effect because it appears that sodium does not cause
      calcium wasting when it is not combined with chloride. More attention to the
      central nervous system effects of dietary calcium is needed. Not only can calcium
      itself influence neural function, but many of the calcium-regulating hormones
      appear to affect the central nervous system. The influence of calcium and calcium
      regulating hormones on central nervous system activity may have important
      implications for blood pressure regulation and also may extend to other aspects
      of physiology and behavior.

PMID- 8144222
TI  - Salt sensitivity in hypertension. Renal and cardiovascular implications.
AB  - The mechanisms responsible for the increase in blood pressure response to high
      salt intake in salt-sensitive patients with essential hypertension are complex
      and only partially understood. A complex interaction between neuroendocrine
      factors and the kidney may underlie the propensity for such patients to retain
      salt and develop salt-dependent hypertension. The possible role of vasodilator
      and natriuretic agents, such as the prostaglandins, endothelium-derived relaxing
      factor, atrial natriuretic factor, and kinin-kallikrein system, requires further
      investigation. An association between salt sensitivity and a greater propensity
      to develop renal failure has been described in certain groups of hypertensive
      patients, such as blacks, the elderly, and those with diabetes mellitus. Salt
      sensitive patients with essential hypertension manifest a deranged renal
      hemodynamic adaptation to a high dietary salt intake. During a low salt diet,
      salt-sensitive and salt-resistant patients have similar mean arterial pressure,
      glomerular filtration rate, effective renal plasma flow, and filtration fraction.
      On the other hand, during a high salt intake glomerular filtration rate does not
      change in either group, and effective renal blood flow increases in salt
      resistant but decreases in salt-sensitive patients; filtration fraction and
      glomerular capillary pressure decrease in salt-resistant but increase in salt
      sensitive patients. Salt-sensitive patients are also more likely than salt
      resistant patients to manifest left ventricular hypertrophy, microalbuminuria,
      and metabolic abnormalities that may predispose them to cardiovascular diseases.
      In conclusion, salt sensitivity in hypertension is associated with substantial
      renal, hemodynamic, and metabolic abnormalities that may enhance the risk of
      cardiovascular and renal morbidity.

PMID- 8144223
TI  - Counselling services for HIV: need of the hour.

PMID- 8144224
TI  - An epidemiological study of cannabis abuse among college students of Varanasi.
AB  - A study of 4326 students, selected by stratified random sampling and using a self
      administered questionnaire, revealed that overall cannabis abuse among them was
      4.5%. It amounted to a considerable decline in prevalence compared to 10.2%
      observed in 1976. However, it was noted that this reduction was mainly in
      occasional users and the proportion of regular users has actually increased in
      1986. The prevalence has also shown an increase among girl students. The regular
      users were mainly from professional colleges, hailing from metropolitan cities
      and with relatively higher amount of pocket money at their disposal. It was
      concluded that the observed trends could be due to peer pressures. It was also
      considered that health education of such students at entry point may help reduce
      the problem.

PMID- 8144225
TI  - Drug consumption pattern in low socio-economic group in an urban community.
AB  - 117 families, having a total population of 558 were studied regarding drug
      consumption pattern. It was found that the average no. of episodes per person was
      0.99 of which drugs were consumed for 72% of episodes. Significant difference was
      observed in consumption of drugs between males and females. Allopathic medicines
      were consumed for 93.3% of the episodes and the major source (53.8%) of medical
      care was from private practitioners. It was seen that the number of drugs
      consumed per episode of sickness rose as the per capita income increased.
      Vitamins and Minerals (22.3%) were the main group of drugs consumed. Drugs acting
      on the alimentary system (17.5%), Respiratory System (14.7%), Antimicrobials
      (14.6%) and Analgesics (10.8%) contributed to 80% of drug intake.

PMID- 8144226
TI  - A study on the impact of awareness programme imparted to in-service nursing staff
      on their knowledge regarding AIDS.
AB  - One hundred five In-service nursing personnel of West Bengal Health Service, who
      completed a two day's orientation training programme on AIDS were subjected to
      Pre and Post-training assessment of their knowledge relating to AIDS by the same
      written questionnaire. Significant improvement in percentage of subjects (from
      7.6% pre-training to 51.4% post-training) with desirable level of awareness and
      knowledge could be achieved by the programme. The importance of inclusion of
      study of AIDS in the pre- qualification curriculum and continuing education for
      nursing personnel is stressed.

PMID- 8144227
TI  - Infant feeding practices in a rural community of west Bengal.
AB  - A study on breast feeding and weaning practices was carried out in a sample of 57
      lactating mothers of rural community. Although early start and prolonged breast
      feeding was an universal practise, but timely weaning was neglected and offered
      to 54.5% of infants only. On the contrary, introduction of artificial milk to
      young infants was a culturally accepted baby feeding.

PMID- 8144228
TI  - Cutaneous leishmaniasis in domestic dogs.
AB  - Cutaneous leishmaniasis was clinically diagnosed by non-healing skin lesions
      present on dorsal surface of nose (Snout) and outer surface of ear and by making
      impression smear from lesions. One per cent Berberine sulphate inoculated
      intralesionally on four occasions at weekly interval was found to be highly
      effective against cutaneous leishmaniasis in domestic dogs.

PMID- 8144229
TI  - Development of epidemiological services and training in India.

PMID- 8144230
TI  - Biologic monitoring of chromium and nickel among stainless steel welders using
      the manual mental arc method.
AB  - Forty manual metal arc welders welding stainless steel (SS) were monitored for 1
      7 workdays measuring total chromium (Cr), water-soluble hexavalent CrVI, and
      nickel (Ni) in the working atmosphere, and Cr and Ni in blood and urine. The mean
      daily increase was 1.0 microgram Cr/l in plasma and 5.6 micrograms Cr/g
      creatinine in urine. There were significant correlations between total Cr and
      CrVI in air and the total Cr in biologic fluids. This was not the case for the
      corresponding correlations for Ni. The observed correlations between urinary and
      plasma Cr levels may permit interchange of these body fluids for biologic
      monitoring at high exposures. The results indicate that urine sampled after work
      is a body fluid versatile for routine monitoring of Cr in SS welders. Smokers had
      higher levels of Cr in biologic fluids than did nonsmokers at equivalent levels
      of air CrVI. The results also indicate that filter masks provide better
      protection against uptake of Cr in the airways than air-stream helmets.

PMID- 8144231
TI  - Association between blood polychlorinated biphenyl concentration and serum
      triglyceride level in chronic "Yusho" (polychlorinated biphenyl poisoning)
      patients.
AB  - The association between blood polychlorinated biphenyl (PCB) concentration and
      serum triglyceride level was investigated in 259 "Yusho" patients (PCB poisoning)
      who underwent health examinations for Yusho in 1988. Geometric means of PCB and
      triglyceride were 3.84 ppb (95% confidence interval: 3.54-4.17) and 114.3 mg/dl
      (106.6-122.6), respectively. Both correlation and multiple regression analyses
      showed a weak but statistically significant correlation between these two
      variables. The mean triglyceride level adjusted for age and sex was then
      calculated for comparison among four PCB levels, using analysis of covariance.
      This indicated a progressive increase with increasing PCB: 98.36, 117.78, 117.84,
      and 127.65 mg/dl at < 2.7, 2.7+, 4.1+, and 6.1+ ppb, respectively (F = 2.01, P =
      0.113). Comparing PCB levels, the difference in adjusted mean triglyceride levels
      was marginally significant between the first and second (P = 0.088), and the
      first and third quartiles (P = 0.066), and reached significance between the first
      and fourth quartiles (P = 0.021). Thus, a weak but significant association
      between blood PCB and serum triglyceride was observed in the patients 20 years
      after exposure, although their blood PCB and serum triglyceride were relatively
      close to the normal levels.

PMID- 8144232
TI  - Biological monitoring and possible health effects in workers occupationally
      exposed to methyl methacrylate.
AB  - Monitoring by means of blood and urine analysis for methanol was successfully
      applied in 32 male workers who were exposed to methyl methacrylate (MMA) monomer
      at 6 ppm as a geometric mean and at 112 ppm as the maximum. Measurement of time
      weighted average (TWA) intensity of the vapor exposure was successfully conducted
      with a diffusive sampler with activated carbon cloth as an adsorbent. Methanol
      concentrations in whole blood, serum, and urine samples were measured by
      headspace gas chromatography. The methanol concentrations in the three biological
      samples collected at the end of 8-h workshifts related linearly with the TWA MMA
      vapor concentrations, with correlation coefficients of 0.8-0.9. Quantitative
      evaluation of MMA in vapor and of methanol in urine suggests that only 1.5% of
      MMA inhaled will be excreted in urine as methanol. There were no significant
      clinical symptoms or abnormal hematological or serum biochemical findings at this
      exposure level, except that some workers complained throat irritation and
      frequent cough and sputa. The results indicate that biological monitoring by
      analysis for methanol is sensitive enough to detect MMA exposure at levels at
      which no serious health effects are to be expected.

PMID- 8144233
TI  - A short-term cross-over study on oral administration of soluble and insoluble
      cobalt compounds: sex differences in biological levels.
AB  - This paper describes a blind cross-over study on the gastrointestinal uptake of
      soluble and insoluble cobalt compounds (8.5 mumol/day) in 12 male and 11 female
      volunteers. In a controlled study it was found that the gastrointestinal uptake
      of the soluble cobalt compound cobalt chloride was considerably higher than the
      uptake of the insoluble cobalt compound cobalt oxide (urine ranges: < 0.17-4373
      and < 0.17-14.6 nmol/mmol creatinine, respectively). Surprisingly, it was shown
      that ingestion of controlled amounts of soluble cobalt compound resulted in
      significantly higher urinary cobalt levels (P < 0.01) in females (median: 109.7
      nmol/mmol creatinine) than in males (median: 38.4 nmol/mmol creatinine). The
      results suggest that the gastrointestinal uptake of cobalt is higher for females
      than males. The present study shows that the normal levels of cobalt in blood and
      urine in a non-random-selected group of Danes are low. As the fraction of values
      below the detection limit of the analytical method was 0.19 and 0.33 for urinary
      cobalt in females and males, respectively, distribution-free one-sided tolerance
      intervals were chosen to describe the values. The precision of the estimate of
      the tolerance intervals was expressed as coverage intervals. In females the 95%
      one-sided tolerance limit calculated for cobalt in blood and urine was 8.48 and
      55.10 nmol/l with coverage intervals of 90% +/- 6.5% and 95% +/- 4.2% at a
      probability of 0.95, respectively. Even though the studied groups of males and
      females were not representative for the general population, the study indicates
      that oral exposure may be important in occupational settings.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8144234
TI  - Urinary excretion of 1-pyrenol in automotive repair workers.
AB  - The urinary excretion of a pyrene metabolite was evaluated in 65 automotive
      repair workers whose skin was exposed to used mineral oils, and in 41 controls.
      Pyrene contents were determined in oily material taken from cloths used to clean
      various types of engines (n = 8) and were found to vary (mean +/- SD) from 2.8 +/
      0.4 ppm for dirty matter obtained from diesel truck engines to 9.3 +/- 8.2 ppm
      for that from petrol car engines. Tobacco smoking and polycyclic aromatic
      hydrocarbon (PAH)-rich diets were considered as confounding factors. At both the
      beginning and the end of the working week, the values of urinary 1-pyrenol were
      slightly higher in exposed subjects (0.178 +/- 0.150 and 0.194 +/- 0.135
      mumol/mol creatinine on Monday and Friday, respectively) than in controls (0.124
      +/- 0.090 mumol/mol creatinine) (Mann-Whitney test, z = 2.741, P < 0.01). The
      urinary 1-pyrenol values were higher in both smoking and non-smoking subjects
      than in controls. The highest values were found in urinary samples of smokers
      exposed to used mineral oils (0.259 +/- 0.201 mumol/mol creatinine). In non
      smoking workers (n = 40), post-shift 1-pyrenol values were 0.154 +/- 0.105
      mumol/mol creatinine, as against 0.083 +/- 0.042 mumol/mol creatinine for the 19
      non-smoking controls (Mann-Whitney test, z = 2.765, P < 0.01). In automobile
      repair workers, urinary 1-pyrenol values before the beginning of the weekly
      workshift did not differ substantially from those measured at the end of the
      week, not being related to the subjective degree of dirty skin as stated by
      workers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144235
TI  - High exposures to organic solvents among graffiti removers.
AB  - The exposure to organic solvents among 12 graffiti removers was studied. Health
      effects were also assessed by structured interview and a symptom questionnaire.
      Blood and urine samples were collected at the end of the day of air sampling. The
      concentrations of dichloromethane, glycol ethers, trimethylbenzenes and N-methyl
      2-pyrrolidinone in the breathing zone of each worker were measured during one
      working day. The 8-h time-weighted average exposure to dichloromethane ranged
      from 18 to 1200 mg/m3. The Swedish Permissible Exposure Limit value for
      dichloromethane is 120 mg/m3. The air concentrations of glycol ethers,
      trimethylbenzenes and N-methyl-2-pyrrolidinone were low or not detectable. No
      exposure-related deviations in the serum concentrations of creatinine, aspartate
      transaminase, alanine transaminase, gamma-glutamyl transpeptidase or hyaluronan
      or the urine concentrations of alpha 1-microglobulin, beta 2-microglobulin or N
      acetyl-beta-glucosaminidase were found. Irritative symptoms of the eyes and upper
      respiratory tract were more prevalent than in the general population. This study
      demonstrates that old knowledge about work hazards is not automatically
      transferred to new professions. Another aspect is that the public is also exposed
      as the job is performed during daytime in underground stations. At least for
      short periods, bystanders may be exposed to high concentrations of organic
      solvent vapours. People with predisposing conditions, e.g. asthmatics, may risk
      adverse reactions.

PMID- 8144236
TI  - Environmental stresses and strains in an extreme situation: the repair of
      electrometallurgy furnaces.
AB  - Whenever continuous casting furnace breaks down, the emergency intervention
      necessary to repair it has to be carried out under exceptional environmental
      conditions caused mainly by heat, as the furnace must be stopped for the shortest
      possible time. In this study, we aimed to evaluate the stresses and strains to
      which boilermakers are subjected during the replacement of an electrode element
      of a 20 MW furnace. The thermal stress was evaluated by the wet bulb globe
      temperature (WBGT) index. CO2 was measured continuously at the furnace periphery
      and sporadically in the center of the furnace using an electrochemical method,
      while CO was also measured in both areas, using Drager tubes. Dusts were sampled
      by a CPM3 (Andersen particle fractionating sampler) and a CIP10 (personal
      sampler). The strain was evaluated by continuous ECG recording with an Aclan IFC
      85, breathing performance was assessed with an HI 298 microspirometer, and blood
      oxygen saturation was evaluated using a Biox oximeter. Thermal stresses are
      extreme: WBGT was 55 degrees C in the furnace center and 34 degrees C in the
      furnace periphery. In spite of the ventilation, the reduction in heat during the
      6 h of the intervention was negligible and did not provide sufficient cooling.
      The analysis of gases and dusts were of minor interest, although the mean CO
      level at the furnace periphery was 40 ppm, with a peak level of 140 ppm in
      furnace center. CO2 and SO2 levels did not exceed TLV-TWA and TLV-Stel
      values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144237
TI  - After-effects of night work on physical performance capacity and sleep quality in
      relation to age.
AB  - The after-effects of night work on physical performance capacity and sleep
      quality were studied. Ten younger (age < or = 34 years) and eight older (age > 34
      years) experienced shift workers were examined. Subjects performed cycle
      ergometer tests at an exercise intensity requiring 70% of the individual maximal
      oxygen uptake. Two conditions were studied: a baseline condition, i.e. the last
      day of a 4 days-off period, and a recovery condition after a period of seven
      consecutive night shifts, i.e. the second day-off after the night-shift period
      (32 h after leaving the night-shift period). Sleep quality of the sleep period
      preceding the test was also measured for both conditions. During the recovery
      condition the endurance time (i.e. time to exhaustion) was reduced by an average
      of 20% (-160s, P < 0.05) for the older shift workers only. In both age groups
      exercise ventilation, heart rate, oxygen uptake, perceived exertion and sleep
      quality remained unaffected. These findings support the hypothesis that the aging
      shift worker is faced with increasing complaints, even after the night-shift
      period. However, to clarify the mechanisms responsible for these after-effects of
      night work, further extensive studies must be designed.

PMID- 8144238
TI  - A field study on the immediate effects of exposure to low-altitude flights on
      heart rate and arrhythmia in patients with cardiac diseases.
AB  - Noise from low-altitude military flights differs from most other sources of noise
      by virtue of its unpredictability in space and time, its very high maximal
      levels, and the fast increase in noise level at high flight speeds. While this
      makes low-altitude flights a frightening and annoying experience, the potential
      immediate health hazards for exposed individuals with preexisting cardiovascular
      disease are unclear. A field study on the immediate effects of exposure to low
      altitude flights on heart rate and arrhythmia was conducted among patients of a
      rehabilitation clinic for cardiac diseases in the summer of 1990 in Bad
      Rothenfelde, Germany. Twenty-four hour electrocardiograms of 68 patients taken on
      days when low-altitude overflights with peak sound pressure levels above 95 dB(A)
      were registered on the flat roof of the clinic were analyzed for changes in the
      heart rate or the occurrence of ventricular extrasystoles in four 2-min periods
      before, around, and after the overflights. Overall, 149 "overflight events" were
      included in the analysis. No major changes in the heart rate or in the frequency
      of ventricular extrasystoles were observed, but this could be partly due to
      problems inherent in the field approach. Nevertheless, the potential effects on
      heart rate and arrhythmia of low-altitude flights appear to be of limited
      magnitude compared to the potential effects of other factors, such as
      psychological or physical exposures, and they are probably too small to be proven
      under field conditions in an observational epidemiologic study in Germany
      following the limitations placed on the frequency and altitude of flights in
      September 1990.

PMID- 8144239
TI  - Asbestos exposure according to different exposure indices among Finnish lung
      cancer patients.
AB  - During a 6-month period all lung cancer patients in a university hospital chest
      clinic were investigated for asbestos exposure by means of personal interview,
      bronchoalveolar lavage (BAL), roentgenograms, lung function testing, histology
      and measurement of fibre concentrations in lung tissue samples using scanning
      electron microscopy (SEM). About one-third of the patients (33%) were classified
      as having been exposed to asbestos on the basis of the interview. BAL was
      performed and AB counts were done in 51 patients. Fourteen (27%) BAL specimens
      had AB counts of 1 or more AB/ml, which is the conventional limit for non-trivial
      asbestos exposure. For a subgroup of 25 operated lung cancer patients fibre
      analysis was also available. In six cases (30%) the asbestos-containing samples
      had asbestos fibre concentrations equal to or more than 1 million fibres/g dry
      lung. In eight (32%) of the operated lung cancer patients histopathologically
      confirmed fibrosis was seen; five of these patients were in the two highest
      exposure classes. Pleural plaques on X-ray films were seen in six (24%) of the
      operated cases. With each indicator of exposure about 30% of lung cancer patients
      were found to have been exposed, confirming the "one-third rule"; however, when
      all the information was collated there were three cases (12%) in which exposure
      was most obvious according to the different parameters used in this study. In
      these three cases the cancer could well be attributed to asbestos. Anthophyllite
      was present in all asbestos-containing samples and anthophyllite was the main
      fibre type in 61% of these samples.

PMID- 8144240
TI  - Biological monitoring of occupational exposure to n-hexane by exhaled air
      analysis and urinalysis.
AB  - To compare two methods of biological monitoring for the evaluation of risk of
      occupational exposure to n-hexane, we analyze the relationship between
      environmental exposure to this solvent and urinary excretion of 2,5-hexanedione
      and n-hexane in exhaled air in 69 workers employed in the shoe industry.
      Environmental exposure to the solvent was monitored with personal diffusive
      samplers, which were desorbed with carbon sulfide and analyzed by gas
      chromatography. To measure 2,5-hexanedione, urine was subjected to acid
      hydrolysis, separation in octadecyl silane columns, elution with 5% aqueous
      acetonitrile solution and extraction with dichloromethane, followed by gas
      chromatography. In exhaled air, n-hexane was measured with a sampling system that
      permitted concentration of aliquots of end-exhaled air (alveolar air) from one or
      more exhalations in a tube packed with activated charcoal, which was then
      desorbed with carbon sulfide and analyzed by gas chromatography. Concentrations
      of n-hexane in breathing zone air were significantly correlated with urinary
      concentrations of 2,5-hexanedione (r = 0.88) and with exhaled air n-hexane (r =
      0.86); in addition, the two biological indicators correlated significantly (r =
      0.70). Analyses in both exhaled air and urine were thus considered useful for
      biological monitoring of the risk of exposure to n-hexane.

PMID- 8144241
TI  - Factors influencing the success of conventional root canal therapy--a five-year
      retrospective study.
AB  - This retrospective study on the outcome of conventional root canal therapy was
      carried out on patients attending the Eastman Dental Hospital between 1970 and
      1982. A minimum follow-up period of 5 years was required for patients to be
      included in the survey. The characteristics of the resulting sample group, the
      techniques for canal preparation and obturation and the obturating materials used
      were analysed. The type of obturating material used had no demonstrable effect on
      success rate but sex, age, preoperative vitality and periapical pathology were
      associated with significantly differing success rates. Technique also influenced
      success rate; the method of canal preparation and the position of the apical seal
      relative to the radiographic apex were both found to be significant. The overall
      success rate was 84.29%, representing 692 of 821 teeth included in the survey.

PMID- 8144242
TI  - In vitro cleaning ability of root canal irrigants with and without endosonics.
AB  - A variety of methods have been used to evaluate the cleanliness of root canals
      after endodontic preparation and irrigation. Few irrigation agents other than
      sodium hypochlorite (NaOCl) have been tested in conjunction with endosonics. The
      purpose of this study was to examine the cleaning ability of water, NaOCl,
      Hibiscrub and a biological washing liquid when used as intracanal irrigants, with
      and without endosonics. Two methods of evaluation were employed to assess the
      root canal cleanliness after endodontic preparation. A total of 56 teeth, divided
      into eight groups, were prepared manually using the step-down technique. Each
      irrigating agent was used in two experimental groups, with and without
      endosonics. Two additional teeth which received neither instrumentation nor
      irrigation served as the controls. The teeth were split longitudinally and the
      state of cleanliness of the root canal was assessed by scoring the amount of
      stained organic debris and smear layer. It was demonstrated that the results of
      debris and smear layer scoring were significantly influenced by the type of
      irrigant and whether endosonics had been used. All agents exhibited similar
      cleaning ability when introduced manually. With endosonics, NaOCl yielded
      significantly less stainable debris (P < 0.05) than the other groups which showed
      no significant difference. The ability to remove the smear layer was enhanced,
      but at some distance short of the working length, by endosonics for all irrigants
      tested. None of the solutions tested was able to produce a canal wall that was
      free of smear layer.

PMID- 8144243
TI  - Presence of natural killer cells in human chronic periapical lesions.
AB  - Natural killer (NK) cells are lymphoid in nature and appear to kill target cells
      (neoplastic and virus-infected cells) without apparent prior immunization. Ten
      human chronic periapical lesions were examined for the presence of these cells.
      The lesions were collected, frozen in liquid nitrogen, and sectioned. They were
      then stained with an indirect immunoperoxidase procedure for the presence of
      human NK cells. Human tonsils and human periapical scar tissue were used as
      positive and negative controls. The results showed absence of NK cells in scar
      tissue and the presence of NK cells in tonsils and all samples of human
      periapical lesions. NK cells may play a defensive role in controlling root canal
      infections or, possibly, a role in its pathogenesis.

PMID- 8144244
TI  - A comparison of endodontic treatment results at two dental schools.
AB  - Endodontic treatment results were assessed in a controlled clinical study in
      Arhus. Undergraduate students used either Kloroperka or AH26 as sealer in a
      randomized fashion. The findings were compared with the results from a previous
      study of identical design in Oslo, which involved Kloroperka, AH26 and ProcoSol.
      While Kloroperka performed slightly, but significantly less well than AH26 or
      ProcoSol in the Oslo study, no difference was found between Kloroperka and AH26
      in the present study. The overall treatment results were poorer in Arhus than in
      Oslo, but this might be explained by a marked difference in the preoperative
      diagnoses and in the technical problems associated with the teeth selected for
      treatment. When results of endodontic treatment carried out at different
      locations are compared, variations in case selection and preoperative diagnoses
      must be corrected for in order to obtain an adequate basis for comparison.

PMID- 8144245
TI  - Antibacterial properties of eight dental cements.
AB  - The antibacterial action of a light-cured glass polyalkenoate Vitrebond and an
      adhesive resin luting agent Panavia Ex was investigated and compared with six
      previously tested dental cements. The bacterial cultures used were six strains of
      Streptococcus mutans, six of Streptococcus sanguis and six cultures of carious
      debris from carious lesions. A modification of the agar diffusion method was used
      to test the antibacterial action of freshly mixed cements. In addition the
      cements were allowed to set and their antimicrobial action was tested by
      incubation for 5 days in sucrose broth inoculated with the test cultures. All the
      freshly mixed materials had an antibacterial action. A two-way analysis of
      variance and Tukey-Student range analysis showed that Vitrebond had a
      significantly greater zone of inhibition than Aquacem, IRM, Dycal, Dycal VLC,
      Ceramco and GC Elite (P = 0.001). Freshly mixed Panavia Ex exhibited minimal
      antibacterial action. After 5 days the antibacterial properties of all the
      cements were reduced.

PMID- 8144246
TI  - Pulpal disease and bursts of periodontal attachment loss.
AB  - Progression of periodontitis is currently thought to occur during bursts of
      activity, followed by periods of remission, when healing may occur. This concept
      contrasts with the older hypothesis that periodontitis was continuously, but
      slowly, progressive throughout life. At present, there is no proof of the
      conventional (microbiological) hypothesis which gives a major role to site
      specific bacteria in the initiation of bursts of attachment loss. An alternative
      hypothesis is presented in this paper which accounts for periodontal attachment
      loss by pathways that are independent of plaque. Severe lesions of the
      periodontium caused by pulpal pathoses (apical and retrograde periodontitis) are
      known to form at any level of the periodontium, not only at the root apex. When
      these lesions cause destruction of the periodontal tissues at the alveolar crest,
      and when plaque, calculus and gingivitis are also present, an endodontic origin
      is rarely suspected. Three pathways are proposed to account for the development
      of localized periodontal attachment loss consequent to pulpal disease. This
      hypothesis accounts for the sudden deterioration of periodontal sites under
      regular review, the strict localization of alveolar defects with normal alveolar
      bone immediately adjacent, the presence of site-specific bacteria (secondary
      colonizers of deep pockets) which cannot cause disease when transferred to
      healthy sites, and the antibody responses directed against them.

PMID- 8144247
TI  - Root canal treatment on patients with HIV infection.
AB  - Patients attending a dedicated dental clinic during the previous 24 months were
      assessed for the success of root canal treatment. Two groups, totalling 48
      patients, had root canal treatment to 57 teeth performed by one operator. All
      treatment was carried out without antibiotic prophylaxis over two or more
      appointments. Patients with HIV infection had root canal treatment to 40 teeth.
      Sixteen patients in the control group had root canal treatment to 17 teeth. Short
      term success was determined by follow-up appointments 1-3 months following
      obturation. No complications were experienced in either group, except with one
      HIV infected patient. The results of this clinical study indicate that root canal
      treatment can be carried out following standard procedures and without antibiotic
      prophylaxis.

PMID- 8144248
TI  - Pediatric trauma in the 90s: an overview.

PMID- 8144249
TI  - Poisoning in the traumatized pediatric patient.

PMID- 8144250
TI  - Pediatric injury patterns.
AB  - Ten thousand pediatric deaths annually in the United States speak for themselves.
      There are distinctive patterns and peculiarities of pediatric injuries that are
      emerging mostly as a result of small epidemiological studies. Trauma research has
      been and continues to be grossly underfunded relative to its impact on society.
      Allocation of appropriate funding and the requisite tools must be made available
      so that targeted and effective prevention campaigns can be designed and
      vigorously implemented [50, 69-75]. We have started, but the bulk of the work
      remains to be done. In many instances we should look to other parts of the world
      for successful examples (United Kingdom, Germany, Australia) [37, 63, 76].
      Greater emphasis must be placed on basic science research applicable to trauma
      and on clinical research designed to improve the care not only of injured
      children but of all trauma patients. While the need for a comprehensive response
      to the worldwide trauma epidemic remains at a whisper, we have started shouting.

PMID- 8144251
TI  - Anesthesia and analgesia for minor injuries to children.
AB  - Today's children are rambunctious, playful, and aggressive and are provided
      through the miracles of modern technology with ample opportunities to injure
      themselves. As such, they are a source of both joy and terror to their parents.
      It is a "given" that many of them will injure themselves in the course of growing
      up. When they come to us in the ED waiting room, they are typically very
      frightened and usually in pain. We are fortunate that we have techniques and
      drugs to alleviate this pain and to attenuate their fear. It is our
      responsibility as anesthesiologists to ensure that these drugs and techniques are
      used appropriately and cause no further harm. We hope the information contained
      in this chapter may be of benefit in achieving this goal.

PMID- 8144252
TI  - Transport of the severely injured child.

PMID- 8144253
TI  - Airway management in the injured child.

PMID- 8144254
TI  - Initial resuscitation and vascular access.

PMID- 8144255
TI  - Blood, fluids, and electrolytes in the pediatric trauma patient.
AB  - Successful resuscitation of pediatric trauma patients begins with identification
      of the physiological abnormalities that require intervention. Health care
      practitioners in the prehospital, emergency room, and operating room settings
      must be familiar with normal physiological parameters to be able to recognize
      abnormalities and begin resuscitative efforts. Recognition of shock may be more
      subtle in the pediatric patient, because blood pressure can be maintained in the
      face of a marked decrease in circulating blood volume. Once recognized, shock
      requires aggressive treatment that must be aimed at supporting and stabilizing
      vital organ function. Obtaining adequate access to the vascular system to carry
      out resuscitation is challenging. The IO method of obtaining access is being used
      with greater frequency when time is critical for resuscitation, as is often the
      case in pediatric trauma. The area of fluid management and blood transfusion has
      undergone extensive change in the last decade but needs continued investigation
      in the pediatric trauma population. Studies targeting this population are
      limited, and current practices are based largely on extrapolation from adult
      experience and studies. The area continues to evolve, but further research is
      needed to improve resuscitation in the pediatric trauma patient.

PMID- 8144256
TI  - Introduction: social and cultural diversity of the oldest-old.
AB  - This introduction describes a volume devoted to a much neglected topic and
      population, the social and cultural diversity among individuals eighty-five years
      old and older. Four articles come from the San Francisco 85+ STUDY: 1)
      comparisons by Colleen Johnson between whites and African Americans in
      socioeconomic status, health, and other outcomes; 2) Barbara Barer's analysis of
      gender differences in the stressors faced in late-life; 3) Charlotte Perry and
      Colleen Johnson's examination of the families of oldest-old African Americans; 4)
      Lillian Troll's analysis of white families. The fifth article by Gloria Clayton
      on rural/urban differences comes from the Georgia Centenarian STUDY. Finally the
      volume concludes with a commentary by Leonard Pearlin that places these studies
      into the broader context of aging research.

PMID- 8144257
TI  - Differential expectations and realities: race, socioeconomic status and health of
      the oldest-old.
AB  - Comparisons by race indicate that African Americans are significantly more
      disadvantaged than whites in their socioeconomic status. Despite complaints about
      their situation, however, African Americans report that their situation is better
      than they had expected. Although they perceive their health as poorer than
      whites, they are no more disabled functionally, and they have significantly
      better morale. Within-group correlations find the predictable associations
      between socioeconomic status and physical, psychological, and social outcomes for
      both groups. Nevertheless, both qualitative and quantitative data indicate that
      economic well-being is related to the congruence between expectations and the
      realities of life in advanced old age, making objective and subjective factors of
      similar importance.

PMID- 8144258
TI  - Men and women aging differently.
AB  - Gender differences in health, socioeconomic status, and social resources persist
      into advanced old age and result in variations in life trajectories and responses
      to the challenges of longevity. The implications of these differences are
      examined in a sample of 150 community-dwelling white men and women. The majority
      are women, a high proportion of whom are unmarried, living alone, functionally
      impaired, and have reduced financial resources. Men, in contrast, have fewer
      decrements, they are more independent, and they exercise more control over their
      environment. However, their well-being may be undermined by some unanticipated
      events such as widowhood, caregiving, and relocation. Case examples illustrate
      how the timing of life course events differs among men and women and results in
      differences in the problems they face in late-late life.

PMID- 8144259
TI  - Families and support networks among African American oldest-old.
AB  - This article examines the demographic profile of oldest-old African-Americans who
      reside in the San Francisco Bay Area. Family life and social support available
      from adult children, relatives, and friends are explored as they vary by gender.
      Bivariate analyses indicate that females receive more help from relatives and
      friends, and males receive more help from immediate family members. Parent and
      childless respondents were compared for instrumental supports. The childless
      received support from a variety of helpers, whereas, the parents received help
      from family or the formal sector. Overall, fewer family members were available to
      assist the oldest-old with community living, although many were able to redefine
      relationships and increase the numbers of helpers available to assist them. These
      findings indicate that the principle of substitution operates among some segments
      of the older African American population, primarily those who are childless. This
      pattern was more evident among females than among males.

PMID- 8144260
TI  - Family-embedded vs. family-deprived oldest-old: a study of contrasts.
AB  - Most of the white oldest-old in San Francisco have at least one surviving
      relative, but only one-half have relatives available to them if they need help.
      The primary family resources are children, especially for women. They are closer
      to children than to grandchildren or other relatives. The respondents themselves
      are more passive and unemotional family members, however, rather than being
      active kinkeepers. They also seem to derive satisfaction from thinking about
      relatives now dead--men usually about their dead wives and women about their
      mothers and siblings. There is a sharp contrast in life style and feelings
      between those who are most embedded in their families and those at the other
      extreme, the "family deprived," with the embedded being much better off.

PMID- 8144261
TI  - The influence of rural/urban residence on health in the oldest-old.
AB  - Differences between rural (n = 18) and urban (n = 66) centenarians are examined
      across the following variables: physical health, activities of daily living,
      mental health, and life satisfaction. Results demonstrate higher levels of morale
      in rural residents and higher levels of functional health as exhibited by urban
      elders. Qualitative data support trends of increased degrees of independence
      among the rural participants. The absence of robust differences in rural and
      urban centenarians is discussed in terms of a leveling-off effect.

PMID- 8144262
TI  - The study of the oldest-old: some promises and puzzles.

PMID- 8144263
TI  - The alcohol-aggression stereotype: a cross-cultural comparison of beliefs.
AB  - University students (N = 1,008) in eight countries participated in a survey aimed
      at mapping cross-cultural alcohol expectancies. Multisample structured means
      analysis was applied to compare changes in aggressive behaviors believed to occur
      in connection with drinking after "many" alcoholic drinks. Most subjects
      expressed the belief that intoxication was associated with greater
      aggressiveness, but there were significant national differences unrelated to self
      reported alcoholic beverage preference, frequency of drinking to intoxication, or
      rates of personal involvement in episodes of alcohol-related aggression. Thus,
      the expectation that drinking leads to aggression may be determined to a
      significant extent by contextual factors and cultural traditions related to
      alcohol use.

PMID- 8144264
TI  - Predicting attrition from substance misuse treatment using the Inventory of
      Interpersonal Problems.
AB  - A simple, self-report scale to predict who would leave substance misuse treatment
      against medical advice was developed and tested. Scale items were drawn from the
      Inventory of Interpersonal Problems which measures interpersonal distress in the
      same format that the SCL-90-R uses to measure personal distress. Potential items
      were selected using data from an initial sample of 66 patients at a substance
      misuse clinic. Factor analytic techniques were then used to decide which of these
      items to include in the scale. It was tested using 98 patients not included in
      the initial sample. Logistic regression analysis confirmed that patients with
      high scores on the scale were significantly more likely to leave treatment than
      were patients with low scores.

PMID- 8144265
TI  - Treatment of female addicts: the importance of relationships to parents,
      partners, and peers for the outcome.
AB  - In an intensive case study, a representative sample of female addicts (n = 13)
      were followed through the total program of a hierarchical TC and again 2 months
      later. The type of relationship to parents was repeated in partner and peer
      relationships, which were strongly related to outcome. All women in the
      nonsuccessful group entered into destructive relationships to male coresidents in
      the outpatient period, while none of the women in the successful group did so.
      Parents, partners, and peer relationships should therefore be in focus during
      treatment, and one should consider whether women should have separate treatment
      programs.

PMID- 8144266
TI  - Effects of alcohol on self-appraisal.
AB  - The present study explored the effects of alcohol on the content of a self
      disclosing speech. Subjects were male social drinkers who received either a 0.85
      g/kg dose of alcohol or a placebo. Subjects presented a 3-minute speech about
      what they liked and disliked about their physical appearance. Audiotapes of these
      speeches were rated by two raters for number and duration of positive and
      negative items disclosed during the speech. Intoxicated subjects disclosed fewer
      negative items than sober subjects. In addition, intoxicated subjects were more
      likely to present negative attributes in a manner that was isolated from their
      self-concept than sober subjects. Alcohol did not affect disclosures of positive
      items. These results suggest that one negatively reinforcing effect of
      intoxication may be the strengthening of self-protective biases.

PMID- 8144267
TI  - Alcohol consumption and correlates among children in the European Community.
AB  - The first survey on adolescent drinking in the European Community in 1990 showed
      that differences in the prevalences of weekly drinkers by country are large.
      Prevalences in Italy and Greece are more than twice the average on the one hand,
      and hardly any child drinks weekly in Ireland on the other. Explanatory variables
      from three scientific domains, i.e., drinking among friends, drinking by parents,
      alcohol permissiveness by parents, pocket money, weekly smoking, and disco
      visits, are related with weekly drinking, confirming the theory of different
      mechanisms.

PMID- 8144268
TI  - Drinking-induced blackouts among young adults: results from a national
      longitudinal study.
AB  - Amnesia drinking episodes among a national probability sample of 12,686 young
      adults are examined at two points in their lives: when they were ages 19 to 26 in
      1984 and 23 through 30 in 1988. Prospective blackout patterns of early onset,
      late onset, chronicity, and remission were analyzed using logistic regression
      statistical models. Results indicate that the relative risk of short-term memory
      loss while drinking is significantly associated with increased alcohol
      consumption, age of drinking onset, the number of alcoholic relatives, and,
      principally, with the individual's capacity to control drinking behavior. It is
      concluded that the blackout remission rate observed among a substantial
      proportion (68%) of young adults may not fit the progressive, irreversible model
      of alcoholism.

PMID- 8144269
TI  - Drug dependence treatment within the Department of Veterans Affairs: emerging
      issues.
AB  - The Department of Veterans Affairs is the largest provider of drug dependence
      treatment services in the United States. However, a national evaluation of
      primarily drug-dependent veterans has never been reported. Findings from the Drug
      Abuse Treatment Services Evaluation Project, a three-year investigation of drug
      dependence treatment within the Department of Veterans Affairs, are discussed.
      Demographic and diagnostic data are presented for the population of 46,047
      inpatients discharged with drug dependence diagnoses in Fiscal Year 1991. Patient
      subtypes and clinical issues of growing relevance to the treatment of drug
      dependent veterans are discussed.

PMID- 8144270
TI  - Psychometric analyses of the Alcohol Dependence Scale among United States and
      Russian clinical samples.
AB  - This project explores the cross-national construct validity of the Alcohol
      Dependence Syndrome. The investigation also examines basic psychometric
      properties of the Alcohol Dependence Scale (ADS), an instrument commonly employed
      to measure dependence. Subjects consisted of inpatients and outpatients in
      American and Russian alcoholism treatment programs. Despite some variations, an
      orthogonal four factor structure of the ADS appears similar across the two
      cultural samples, thus lending support to the alcohol dependence construct.
      Analyses of psychometric properties of the Scale generally support its value in
      future cross-cultural research on alcohol dependence.

PMID- 8144272
TI  - Phases of treatment: a practical approach to methadone maintenance treatment.
AB  - There has been an on-going controversy in the United States as to whether
      methadone should be used in the treatment of opiate addiction as a long-term
      pharmacological treatment or as a short-term medical intervention to help addicts
      attain an opiate-free state. This article describes a practical treatment
      approach which resolves this dichotomy and presents a clinical framework for the
      variable use of methadone to effectively meet the needs of each individual
      patient. The therapeutic process is highly structured and is divided into several
      phases of treatment for opiate addiction. The article describes each of these
      phases and illustrates how they can be translated into clinical/medical practice.
      Some of the issues regarding medical maintenance, as well as methadone tapering
      and maintaining subsequent abstinence, are also addressed.

PMID- 8144271
TI  - Parental drinking and gender factors in the prediction of early adolescent
      alcohol use.
AB  - This study examines the relationship between children's reports of their parents'
      drinking patterns, and the child's alcohol misuse and heavy alcohol use in early
      adolescence. Subjects were 2,213 fifth and sixth grade students. Data on the
      child's alcohol use and misuse, and parent alcohol use, were derived from
      classroom-administered questionnaires. Increased reported level of drinking by
      mother or by father was significantly associated with increased odds of alcohol
      misuse and heavy alcohol use among the children; these results held for both boys
      and girls when examined separately. Examination for possible confounding effects
      of assortative mating by parental drinking suggests that reports of heavy
      drinking in either parent increases the risk of alcohol misuse and heavy alcohol
      use in children. Implications for prevention efforts are discussed.

PMID- 8144273
TI  - A processes of change model for weight control for participants in community
      based weight loss programs.
AB  - The processes of change model has been successful in predicting behavior change
      across a wide range of both addictive and nonaddictive problem behaviors. This
      study was designed to examine the application of the processes of change model to
      weight control. Study participants included 285 women and men enrolled in three
      community-based weight loss programs. Results based on structural equation
      analyses showed that the processes of change model fit the data better than
      several plausible alternative models. In addition, structural analyses revealed
      the existence of two general (higher order) processes of change for weight
      control, the experiential and behavioral processes. These results are similar to
      those previously reported for eight other problem behaviors. Limitations of the
      current work and future directions for this line of research are discussed.

PMID- 8144274
TI  - Illicit drug injectors in three Texas cities.
AB  - In three Texas cities illicit drug injectors not in treatment were located by
      outreach and interviewed with a standard questionnaire. In all the cities the
      drug injectors were predominantly undereducated and unemployed young men from
      minority groups. In Dallas and Houston most were Black, while in San Antonio most
      were Hispanic. The most frequently reported primary drug in Houston was cocaine,
      but in Dallas and San Antonio it was heroin. The high needle risk for AIDS and
      the low rates of positive HIV antibody tests in these samples present a special
      window of opportunity for prevention of AIDS.

PMID- 8144275
TI  - The role of marijuana in homicide.
AB  - In this paper we examine the relationship between marijuana use and homicide.
      Data derive from interviews with 268 individuals incarcerated in New York State
      correctional facilities for homicides that occurred in 1984. We found that in
      terms of lifetime use, marijuana was the most commonly used illicit drug in this
      sample; that about one-third of respondents who had ever used marijuana used the
      drug in the 24-hour period before the homicide; and that almost three-quarters of
      those respondents were experiencing some type of effect from the drug when the
      homicide occurred. A total of 18 respondents (7% of the total sample) said that
      the homicide was related to their marijuana use. We examine the reasons these
      respondents gave for this relationship and the other substances they reported
      using at the time of the homicide. We also demonstrate that from the perspective
      of a conceptual framework that specifies the ways that drugs and violence may be
      linked, there are various nuances in the ways that marijuana and homicide are
      related. We discuss the implications and limitations of using self-report data
      from perpetrators of violence for our understanding of the drugs-violence
      connection.

PMID- 8144276
TI  - Risk factors for drug misuse in Pakistan.
AB  - While a number of risk factors have been identified for drug misuse in the United
      States, little evidence is available about such factors in other societies. This
      study attempted to identify risk factors in Pakistan. Ten of 11 sociodemographic
      variables which had previously been identified as predictors in the United States
      successfully differentiated groups of addicts and controls in Pakistan. About 97%
      of the 60 addicts studied were at risk on four or more factors; 100% of controls
      were at risk on four or fewer factors. It appears that the precursors for misuse
      cut across cultural lines.

PMID- 8144277
TI  - Perceptions and attitudes with respect to drug use among grades 4 to 6 students:
      1992.
AB  - Over 2,600 students in Grades 4 to 6 participated, over a 1-year period ending
      June 30, 1992, in a survey to determine perceptions and attitudes of drug use.
      While the majority of students did not use drugs, the survey revealed some
      interesting perceptions. Not all students were aware drugs could be harmful to
      their health. They indicated using drugs makes you look older, feel good, and get
      attention. Some felt drugs might be used to be like their friends. This age group
      of students are obviously very aware of the "drug scene." It is imperative that
      education start at a very young age.

PMID- 8144278
TI  - Childhood victimization and risk for alcohol and drug arrests.
AB  - Using data from a prospective cohorts design study, this paper examines the
      relationship between early childhood victimization and subsequent arrest for
      alcohol- and/or drug-related offenses. Complete official criminal histories are
      compared for cases of childhood physical and sexual abuse and neglect (n = 908)
      and a control sample (n = 667). After controlling for relevant demographic
      characteristics, logistic regression analyses indicate that childhood
      maltreatment is a significant predictor of adult, but not juvenile, arrests for
      alcohol- and/or drug-related offenses. Differential responses to maltreatment by
      race and gender are discussed as well as limitations of the findings and future
      directions for research.

PMID- 8144279
TI  - Sex differences in self-report of physical health by injection drug users.
AB  - Through heterosexual contact, injection drug users (IDUs) put others at risk of
      contracting Human Immunodeficiency Virus (HIV) disease. Self-report of health was
      compared among IDUs in Laredo, Texas, San Diego, California, and San Juan, Puerto
      Rico, and in a subsample which contained HIV positive subjects from these cities.
      These data were compared with similar National Opinion Research Center data and
      indicated that IDUs do not report their health to be different from that of the
      general public. Previous research has reported sex differences in morbidity and
      mortality in the non-IDU population. This study found sex differences in
      perception of health by IDUs in Laredo and San Diego.

PMID- 8144280
TI  - The influence of medical conditions associated with hormones on the risk of
      breast cancer.
AB  - Medical conditions related to hormonal abnormalities were investigated in a case
      control study of breast cancer among women who attended a screening centre.
      Information was obtained by telephone interview regarding physician-diagnosed
      medical conditions such as thyroid or liver diseases, diabetes, and hypertension,
      as well as hirsutism, acne, galactorrhoea, and reproductive, menstrual, and
      gynaecological factors. Results are presented for 354 cases and 747 controls.
      Women with fertility problems who never succeeded in becoming pregnant were at
      significantly increased breast cancer risk (adjusted odds ratio [OR] = 3.5; 95%
      confidence interval [CI]:1.1-10.9). An elevated cancer risk was also associated
      with having excess body hair (OR = 1.5; 95% CI:1.0-2.3), or having excess body
      hair in addition to persistent adult acne (OR = 6.8; 95% CI:1.7-27.1). Recurrent
      amenorrhea (OR = 3.5; 95% CI:1.1-11.5), and a treated hyperthyroid condition (OR
      = 2.2; 95% CI:1.1-4.4) were significantly associated with risk. A non-significant
      elevation of risk was present for endometrial hyperplasia (OR = 1.8; 95% CI: 0.8
      4.0). There was a suggestion of an association between a history of galactorrhoea
      and breast cancer risk (OR = 2.0; 95% CI:0.8-4.9) among premenopausal women. No
      associations were found with other medical or gynaecological factors. The
      possibility that some of these findings are due to chance cannot be excluded
      because of the problem of multiple comparisons.

PMID- 8144281
TI  - Cancer in a young population in a dioxin-contaminated area.
AB  - An industrial accident in Seveso, Italy, in 1976, caused contamination of the
      residential community with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We
      investigated cancer occurrence in the first post-accident decade (1977-1986)
      among nearly 20,000 subjects aged 0-19 years. People who left the area were
      actively followed with a 99% follow-up rate. For reported cancer cases
      confirmation was obtained through consultation with original medical records. Two
      ovarian cancers were observed versus none expected. A suggestive increase was
      seen for Hodgkin's lymphoma (relative risk [RR] = 2.0; 95% confidence interval
      [CI] = 0.5-7.6). Myeloid leukaemia showed a clear, but not statistically
      significant increase (RR = 2.7; 95% CI = 0.7-11.4). The most prominent result
      concerned thyroid cancer, not just for the magnitude of the increase (two cases,
      RR = 4.6; 95% CI = 0.6-32.7), but also for its consistency with experimental
      findings and previous observations in humans. Any conclusive interpretation would
      be premature because of the short time since initial exposure, ecological
      definition of exposure status, and limited number of events.

PMID- 8144282
TI  - Diet and heart disease risk factors in adult American men and women: the
      Framingham Offspring-Spouse nutrition studies.
AB  - The 1984-1988 dietary and cardiovascular disease risk factor profiles of the
      Framingham Offspring-Spouse population (n = 3787 Framingham males and females, 22
      79 years) were compared to earlier estimates from the 1976-1980 NHANES II and
      1977-1978 USDA Nationwide Food Consumption surveys. The goals were to assess
      whether differences exist among population estimates, to determine whether
      national population-based nutrition recommendations for cardiovascular disease
      risk reduction are appropriately targeted, and to identify focus areas for future
      preventive nutrition interventions. Overall, population mean levels of
      cardiovascular disease risk factors were high but mean total cholesterol and
      blood pressure levels and rates of dyslipidaemia were lower in Framingham men and
      women and hypertension appeared higher in Framingham compared with NHANES II.
      Severe overweight appeared more prevalent in Framingham men but similar in
      Framingham women in comparison with NHANES. Population estimates of total fat (36
      41% of calories) and saturated fat (12.5-13.7% of calories) intakes were higher
      and carbohydrate intakes were lower (40-46% of calories) than current recommended
      levels. Dietary cholesterol and sodium intakes in Framingham women appeared to
      have reached recommended levels but were high in men. While the goals of current
      nutrition recommendations remain appropriate, future population-based preventive
      nutrition interventions to lower cardiovascular disease risk need to emphasize
      weight reduction, lowering intakes of foods rich in animal and plant fats,
      increases in dietary sources of complex carbohydrates, fibre and micronutrients,
      and lower sodium intakes, particularly in adult men.

PMID- 8144283
TI  - Changing social patterns of risk factors for cardiovascular disease in a Swedish
      community intervention programme.
AB  - Since 1985 a small-scale community-based cardiovascular disease (CVD) preventive
      programme has been in operation in an inland municipality, Norsjo, in Northern
      Sweden. The aim of this study was to assess the development of the relationship
      between social position and CVD risk factors in repeated cross-sectional surveys
      (1985-1990) among all men and women aged 30, 40, 50 and 60 years in the study
      area, using an age-stratified random sample from the Northern Sweden MONICA Study
      of 1986 and 1990 as reference population. These multiple cross-sectional surveys
      comprised a self-administered questionnaire and a health examination. Of the
      study population 95% (n = 1499) and 80% of those in the reference area (n = 3208)
      participated. Subjects were classified with regard to demographic, structural and
      social characteristics in relation to CVD risk factors and self-reported health
      status. Time trends in classical risk factor occurrence were assessed in terms of
      age- and sex- adjusted odds ratios using Mantel-Haenszel procedures. When
      simultaneously adjusting for several potential confounders we used a logistic
      regression analysis. Initially, more than half of the study population, both
      males and females, had and elevated (> or = 6.5 mmol/l) serum cholesterol level.
      After adjustments had been made for age and social factors it was found that the
      relative risk of hypercholesterolaemia dropped substantially and significantly
      among both sexes during the 6 years of CVD intervention in the study area.
      However, the probability of being a smoker was significantly reduced only in
      highly educated groups. Among other risk factors no single statistically
      significant change over time could be found. In the reference area there were no
      changes over time for the selected CVD risk factors. People in the study area had
      a less favourable perception of their health than those in the reference area.
      Social differences were found when perceived good health was measured, especially
      in variables indicating emotional and social support. When sex, age and social
      factors had been accounted for there was not clear change over the years in
      perceived good health.

PMID- 8144284
TI  - Changes in total serum cholesterol and other risk factors for cardiovascular
      disease in Japan 1980-1989.
AB  - To monitor recent changes in Japan in diet and risk factors for cardiovascular
      disease (CVD), in the light of the decline on coronary heart disease, total serum
      cholesterol levels and other risk factors were compared between two nationwide
      health surveys in 1980 and 1989 conducted in the same population as the annual
      National Nutrition Surveys. Between 1980 and 1989, age-adjusted total serum
      cholesterol levels increased from 4.84 to 5.22 for men and from 4.91 to 5.24
      mmol/l for women. Prevalence of age-adjusted hypercholesterolaemia of > or = 5.68
      mmol/l (220 mg/dl) increased from 15.8% to 29.4% for men and from 18.4% to 30.6%
      for women. Decline in blood pressure was observed for both sexes. Prevalence of
      smoking decreased from 64.7% to 58.7% in men while prevalence in women remained
      low (from 10.1 to 9.9%). Considerable increases in total serum cholesterol levels
      do not offer an explanation of the recent decline in mortality from coronary
      heart disease in Japan. This may, in part, be related to a decline in blood
      pressure levels.

PMID- 8144285
TI  - Cardiovascular risk factors in the Republic of Karelia, Russia, and in North
      Karelia, Finland.
AB  - Cardiovascular disease risk factors were measured in a population survey in
      Pitkaranta District in the Republic of Karelia and in North Karelia in Finland in
      spring 1992. According to official statistics the cardiovascular mortality in the
      Republic of Karelia is somewhat higher, and total mortality and cancer mortality
      considerably higher than in North Karelia. A random sample of the population,
      aged 25-64 years, was taken in Pitkaranta (n = 1000) and in North Karelia (n =
      2000). The participation rates were 84% and 74% respectively. The mean total
      serum cholesterol among men was 5.2 mmol/l in Pitkaranta and 5.8 mmol/l in North
      Karelia (P < 0.001) and among women 5.3 mmol/l and 5.6 mmol/l (P < 0.001),
      respectively. The mean high density lipoprotein (HDL) cholesterol levels among
      men were 1.4 mmol/l and 1.3 mmol/l (P < 0.001), and among women 1.4 mmol/l and
      1.5 mmol/l (P < 0.001), respectively. There were no significant differences in
      blood pressure among men, but women in Pitkaranta had higher blood pressure than
      women in North Karelia. The mean body mass index in Pitkaranta was higher among
      women, 28.0 versus 26.5 (P < 0.001) and lower among men, 25.2 versus 27.0 (P <
      0.001) than in North Karelia. Smoking was much more common among men (65% versus
      31%) but less common among women (10% versus 16%) in Pitkaranta than in North
      Karelia. The general level of the risk factors, and especially the higher
      prevalence of smoking among men could explain the high mortality rates in
      Pitkaranta, and in particular the high cancer mortality.

PMID- 8144286
TI  - Gender differential in all-cause and cardiovascular disease mortality.
AB  - The gender differential in mortality from all causes, cardiovascular disease
      (CVD), ischaemic heart disease (IHD) and stroke during the mean follow-up of 11.6
      years (range 10-14) was examined among 4696 men and 5714 women aged 45-64 at
      entry in West of Scotland. Overall mortality was 19.4/1000 person-years of
      observation among men and 10.8/1000 person-years among women. A multiple logistic
      regression model was used to control the influence of gender, along with seven
      other cardiovascular risk factors simultaneously. The risk factors considered
      were age, systolic (SBP) and diastolic blood pressure (DBP), serum cholesterol,
      causal blood glucose, body mass index (BMI) and cigarette smoking. Both the
      prevalence of risk factors and relative mortality risk associated with them
      differed by gender. Adjustment slightly reduced the gender differential in
      overall mortality from 2 to 1.9 and from 1.5 to 1.4 for stroke deaths. Multiple
      logistic regression increased minimally the gender differential for mortality
      from 2.4 to 2.8 for CVD and from 2.8 to 3.4 for IHD, suggesting that these
      cardiovascular risk factors do not account for the overall gender difference in
      mortality rates. Age, SBP, DBP, blood glucose and cigarette smoking were
      significant predictors of mortality for both genders. Serum cholesterol was a
      statistically significant predictor of CVD death only for men.

PMID- 8144287
TI  - Consistency in children's recall of age of initiating smoking.
AB  - Studies of the accuracy of long-term recall for information about smoking status
      have tended to conclude that this information is consistent and reliable.
      Estimation of consumption levels have been found to be less reliable and can be
      influenced by current consumption levels. Results of this longitudinal study
      indicated that children's and adolescents' 2-year recall of smoking status was
      inconsistent and that children's reports of age of initiating smoking showed an
      unacceptably high level of misclassification, particularly if they had not smoked
      in the last 2 years. Children's and adolescents' 2-year recall for the age at
      which they first smoked were imprecise and suggested that those who had smoked in
      the last 2 years retained a perspective as they grew older of having started in
      the last few years. It is recommended that the period of recall for children and
      adolescents be restricted to no more than 1 year.

PMID- 8144288
TI  - Issues of rescue and medical care following the 1988 Armenian earthquake.
AB  - On-site emergency care and rescue efforts may be critical in preventing
      disability and other serious consequences of disasters. In this report we compare
      efforts used in the rescue and emergency medical care of 189 people (case
      subjects) from Kumairy (Leninakan), Armenia, who were hospitalized with serious
      injuries following the Armenian earthquake of 7 December 1988, with efforts used
      in helping 68 people (controls) from Kumairy with mild injuries who were not
      hospitalized. We used a standardized interview questionnaire to ascertain the
      circumstances of entrapment, the rescue process used, the injuries the victims
      sustained, and the medical care they received. Case and control subjects shared
      similar social and demographic characteristics; however, case subjects waited
      longer to be rescued and to receive medical care than did control subjects. Of
      the people who said they were trapped, 66.2% of the case subjects and 41.2% of
      the control subjects said that they were trapped for > 1 hour (odds ratio [OR] =
      2.79, 95% confidence interval [CI]: 1.52-5.13) whilst the OR for > 6 hours of
      entrapment was 3.88 (95% CI: 1.69-9.10). Of those requiring medical care, 28.6%
      of people who were hospitalized waited > 1 hour after rescue to receive medical
      care, compared with only 14.7% of the control subjects (OR = 2.32, 95% CI: 1.05
      5.23). In addition to the case-control study, we collected data on general
      characteristics of the rescue and emergency medical care process. We found that
      most of the trapped people were rescued by untrained local inhabitants who most
      often used their hands or simple tools.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144290
TI  - The epidemiology of peptic ulcer mortality 1953-1989: a birth cohort analysis.
AB  - Peptic ulcer (PU) disease is the cause of substantial morbidity and mortality in
      a number of countries including Australia. Despite diagnostic and treatment
      advances, sustained mortality from PU disease has been reported. To understand
      this problem a birth cohort analysis using the Median Polish Technique (MPT) was
      performed on 36 years of mortality data from New South Wales, Australia. The MPT
      allows cohort effects to be quantified, yet has rarely been applied to mortality
      data. Birth cohort effects detected using graphical presentation of mortality
      data for duodenal (DU) and gastric ulcer (GU) mortality data for both males and
      females, were supported by the results obtained using the MPT. The DU mortality
      rates for females increased significantly over the 36-year period. This increase
      can be explained by the presence of a birth cohort effect, with women born
      between 1898 and 1913 having a greater risk of dying from DU than preceding or
      subsequent generations. Cohort effects in GU and DU mortality data for males and
      in GU mortality for females were also present, although these were masked by the
      overall decline in PU mortality rates. The results support the findings of other
      studies of birth cohort effects in PU mortality data from England, Europe and
      Japan, and provide support for the existence of environmental factors which
      resulted in increased PU mortality among specific birth cohorts. Demonstration of
      these birth cohort effects should influence the theories of PU disease aetiology
      and prevention and should be considered in developing approaches for further
      research.

PMID- 8144289
TI  - Mortality among people affected by toxic oil syndrome.
AB  - The authors conducted a mailed questionnaire survey of a 5% sample of the cohort
      of 20,643 people officially recognized by the Spanish government as having had
      toxic oil syndrome, a previously undescribed illness that was epidemic in Spain
      in 1981. After three mailings of a letter and questionnaire, responses for only
      66% of the sample had been received. Nevertheless, responses were obtained from
      virtually all remaining patients (or surrogates for them in the cases of patients
      that had died) when they were sought by telephone. In 1981, there was clear-cut
      excess mortality in the cohort (standardized mortality ratio [SMR] 6.51; 95%
      confidence interval [CI]: 3.92-10.17). During the period January 1982 through 7
      March 1988, there was no statistically significant overall mortality excess
      except during the period 1982-1983 among people aged < 65 years (SMR 2.26; 95%
      CI: 1.03-4.29). Toxic oil syndrome substantially altered the patterns of
      mortality among affected people. Analysis of deaths by cause among the TOS cohort
      will be useful for further evaluation of the long-term impact of the TOS
      epidemic.

PMID- 8144291
TI  - Abdominal symptom associations in a longitudinal study.
AB  - The aim of the study was to assess the association of abdominal symptoms in a
      random sample of a general population and to find whether the associations could
      be confirmed at follow-up 5 years later. The study population was a sex- and age
      stratified random sample of people living in the western part of Copenhagen
      County, Denmark. Of 4807 eligible subjects 79% attended the study and filled in a
      questionnaire on abdominal symptoms. Five years later the study was repeated and
      85% of the survivors participated. Data from both studies were analysed
      separately for sex, age group and the following pain variables: unspecified
      abdominal pain, pain located to the epigastrium, pain provoked by stress or
      hunger, pain relieved by eating and pain relieved by defecation. Three clusters
      of symptoms occurred in all the analyses: borborygmi/altering stool
      consistency/distension; acid regurgitation/heartburn and nausea/vomiting.
      Unspecified pain was associated with all three clusters, pain provoked by stress
      or hunger and pain relieved by defecation associated with the borborygmi/altering
      stool/distension cluster, whereas pain in the epigastrium and pain relieved by
      eating did not show consistent relationships to any of the clusters.
      Additionally, the clusters associated with each other more often than could be
      expected by chance. As a consequence of our findings we suggest that the three
      clusters of symptoms constitute three common abdominal syndromes.

PMID- 8144292
TI  - Use of oral moist snuff and inflammatory bowel disease.
AB  - We examined the association between oral moist snuff use and inflammatory bowel
      disease in a case-control study based on the population in Stockholm County. The
      relative risk (RR) associated with ever use of moist snuff was 2.1 (95% CI: 1.0
      4.6) for Crohn's disease, and 2.2 (95% CI: 1.1-4.4) for ulcerative colitis.
      Cigarette smoking indicated a synergistic relation with moist snuff: the RR
      estimate of Crohn's disease was 3.7 (95% CI: 1.1-13.1) and of ulcerative colitis
      3.3 (95% CI: 1.0-10.9) for snuff dippers who were also current cigarette smokers,
      but only 0.9 and 1.1 respectively for snuff dippers who had never smoked.

PMID- 8144293
TI  - Child morbidity patterns in two tropical seasons and associated mortality rates.
AB  - Cross-sectional morbidity recorded during two successive quarterly survey rounds
      and subsequent 27-months mortality were studied in a random sample of 4238
      preschool children in a rural Zairian area. Analysis focuses on morbid patterns,
      i.e. any combination of the principal signs and symptoms encountered in tropical
      areas (oedema, marasmus, cough, fever, diarrhoea and tachypnoea). Almost half the
      children (45-48%) had signs of morbidity, a very high rate. The 3-6 month age
      group emerged as particularly vulnerable with the highest prevalences of all
      morbid patterns except for isolated fever. Isolated cough was more prevalent in
      the dry season probably as an effect of nightly indoor woodburning. All other
      morbid patterns were significantly more prevalent in the rainy season. Diarrhoea
      with cough was found to constitute half of all cases of diarrhoea. The results
      show that with a few simple questions on major symptoms and a brief examination
      by paramedical health workers, children with an increased risk of death can be
      identified. The method can be applied at under-5 clinics. Prognosis is
      particularly bad in severe malnutrition, especially when associated with
      diarrhoea, in diarrhoea with cough, cough with fever/tachypnoea and for children
      who are found sick both in the rainy and the subsequent dry season.

PMID- 8144294
TI  - Evaluation of indicators for use in vitamin A intervention trials targeted at
      women.
AB  - This paper examines the ability of three indicators to detect changes in women's
      vitamin A status. Serum retinol concentration, milk vitamin A concentration, and
      milk vitamin A per gram milk fat were used to assess the vitamin A status of
      mildly deficient Indonesian women before and after supplementation in a
      randomized intervention trial. Choice of indicator made a fourfold difference in
      the sample size required to measure a statistically significant change in vitamin
      A status. Milk vitamin A per gram milk fat was the best indicator of response,
      milk vitamin A concentration was intermediate, and serum retinol concentration
      performed most poorly. Serum retinol concentration was equally responsive across
      the range of vitamin A status in this population. The milk indicators were more
      responsive among women of lower status than women of higher status. Milk vitamin
      A is an efficient indicator for monitoring the effects of vitamin A interventions
      in women.

PMID- 8144295
TI  - Determinants of night blindness in Bangladesh.
AB  - A cross-sectional study was conducted to evaluate the effect of a community-based
      health education intervention programme and to study the determinants of night
      blindness in Bangladesh. The intervention programme was implemented to reduce the
      morbidity of nutritional blindness (night blindness) in the northern part of
      Bangladesh (Ranjpure district) during 1986-1989. A baseline study in 1986 covered
      2010 households with a total population of 11,600, and the evaluation study in
      1989 covered 2011 households with a total population of 10,456. Prevalence of
      night blindness was studied among children aged < 9 years in these households.
      The prevalence of night blindness per 1000 children was reduced significantly
      during the intervention period from 50.7 in 1986 to 26.7 in 1989. However, the
      post-intervention prevalence varied significantly between areas. Multivariate
      analyses showed that consumption of fish, meat, milk or eggs, dark green leaf
      vegetables, yellow fruits and vitamin A capsules were significant predictors of
      night blindness. In addition, family income, mother's literacy, family size and
      area of residence exhibited strong and statistically significant associations
      with night blindness in the 1989 cross-sectional study. The prevalence of night
      blindness was highest among 4-6 year old girls and 7-8 year old boys. The sex
      difference was, however, not statistically significant.

PMID- 8144296
TI  - Geographical variation of Legionnaires' disease: a critique and guide to future
      research.
AB  - This review considers the value of the observation that Legionnaires' disease
      varies geographically. Estimates of disease incidence, derived from case
      registers and from studies measuring the proportion of cases of pneumonia which
      are Legionnaires' disease, and of the prevalence of the population with antibody,
      show that there is geographical variation in disease frequency. Much, but not
      all, of this variation is artefact due to differences in definitions, diagnostic
      methods, surveillance systems and data presentation. Some of the variation is
      attributed to publication bias, e.g. in 10 small studies (< 100 patients) 13.2%
      of pneumonia patients had Legionnaires' disease but in five large studies (> or =
      500 patients) the figure was 3.6%. Research to explain variations has been
      neglected but a few studies have provided important insights into disease
      transmission. Future studies should: be based on agreed disease definitions and
      data collection and analysis methods; analyse subgroups separately; and collect
      data to develop explanations for geographical variation.

PMID- 8144297
TI  - Cross-sectional household surveys of diarrhoeal diseases--a comparison of data
      from the Control of Diarrhoeal Diseases and Demographic and Health Surveys
      programmes.
AB  - Cross-sectional household surveys are extensively used for data collection,
      priority setting and programme evaluation in developing countries. They are now
      being promoted to assess a number of health care interventions such as Control of
      Diarrhoeal Diseases (CDD), Expanded Programme on Immunization (EPI), AIDS control
      and child survival programmes. Few field studies of the validity and precision of
      data generated from these surveys have been carried out, in part because such
      work is rather demanding of resources. The purpose of this study was to draw
      conclusions on validity and reliability of data from household surveys through a
      comparison of results from large-scale surveys on diarrhoea conducted by CDD and
      Demographic and Health Surveys (DHS) programmes in developing countries.
      Diarrhoea prevalence and treatment were compared for nine surveys for which
      little time had passed in between the CDD and DHS survey. The variation in
      results between the surveys was in many instances too large to be explained only
      by a true variation in the variable studied. A literature review suggested that
      validity problems could be due to response and recall errors. The authors caution
      the use of frequent household surveys for programme impact evaluation. Their cost
      effectiveness should be carefully assessed, especially when services' evaluations
      already have provided evidence that a programme has had a positive effect on the
      behaviour of health workers and target groups in the community. It is recommended
      that more research be carried out on how selection and training of surveyors can
      be improved to make the quality of household surveys in developing countries
      better.

PMID- 8144298
TI  - Factors affecting immunization coverage levels in a district of India.
AB  - Immunization coverage is measured to assess the performance of the Expanded
      Programme on Immunization. In 1988 we conducted a coverage survey among 12-23
      month-old children in the North Arcot District (population 5,007,746) in southern
      India. In each of the 12 towns a 30-cluster sample survey was conducted. In the
      35 rural blocks with 1590 panchayats, 159 were selected systematically and all
      children (n = 7300) were surveyed. In the towns, coverage ranged for measles
      vaccine from 29 to 53%, BCG from 65 to 91% and OPV and DPT third dose from just
      over 60% to just over 80%. In the rural areas, coverage ranged for measles
      vaccine from 10.8 to 19.3%, BCG 25.1-34.1%, DPT third dose 42.2-50.4% and OPV
      third dose 39.6-48%. In the towns, 25, 66, 67 and 59% of BCG, DPT, OPV and
      measles vaccines had been provided by private agencies showing that availability
      of vaccines throughout the week and easy access even in payment terms played an
      important role in achieving higher levels of coverage compared with rural areas
      where all vaccines are given by Government agencies, free of charge. In the rural
      areas, significantly large variations in coverage were seen among panchayats-
      large and peri-urban panchayats had significantly better coverage than small and
      more rural panchayats. Within any given block (the population unit consisting of
      30-40 panchayats served by a Primary Health Centre), there were large variations
      in the levels of immunization coverage between panchayats.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8144299
TI  - Protective effect of BCG against tuberculous meningitis and miliary tuberculosis:
      a meta-analysis.
AB  - The protective effect of BCG against tuberculosis (TB) estimated in randomized
      controlled trials and observational studies ranges from negative to close to a
      100%. One of the many explanations offered for this is that different
      immunological mechanisms may be associated with protective effect against
      different forms and sites of disease. In this investigation, we recalculated
      vaccine protective effect separately for pulmonary disease and for
      meningeal/miliary disease in randomized controlled trials and case-control
      studies, tested for heterogeneity in site-specific estimates of protective effect
      and calculated a summary measure when appropriate. We found protective effect
      against pulmonary disease to be heterogeneous to a statistically significant
      degree, and thus we did not calculate a summary measure of protection. Protective
      effect against meningeal and miliary TB was higher than against pulmonary disease
      and, except for a single study with two cases only, appeared to be homogenous.
      Summary BCG protective effect against miliary or meningeal TB in randomized
      controlled trials was 86% (95% confidence interval [CI] 65, 95) and in case
      control studies 75% (95% CI: 61, 84). The fact that protective effect appeared to
      be homogeneous against meningitis and miliary TB but not against pulmonary
      disease may result from the fact that patients with meningitis are on average
      younger and thus less likely to have been exposed to atypical bacteria; to a
      waning of the protective effect of BCG; or from the diversity of mechanisms of
      pathogenesis of pulmonary disease, which can originate from reinfection,
      reactivation or primary progression.

PMID- 8144300
TI  - HIV-1 infection as a risk factor for the development of tuberculosis: a case
      control study in Tanzania.
AB  - A population-based case-control study was carried out in Mwanza Region, Tanzania,
      to determine the relative and population attributable risk of human
      immunodeficiency virus type 1 (HIV-1) infection for developing active
      tuberculosis. Cases were 441 consecutively diagnosed patients with tuberculosis
      (all types), aged 15-54 years. Controls were a representative population sample
      of 4161 people, drawn in a stratified cluster sample from urban areas, roadside
      settlements, and rural villages. HIV-1 infection was determined by ELISA and if
      the ELISA result was indeterminate by Western Blot. The HIV-1 prevalence in cases
      was 23.0% in rural, 32.1% in roadside, and 54.1% in urban areas, while in
      controls these prevalences were 3.4%, 7.2% and 12.1% respectively. The relative
      risk (RR) of HIV-1 infection for the development of active tuberculosis was
      estimated to be 8.3 (95% confidence interval [CI] 6.4-11.0). This risk varied
      little by sex or residence, but appeared to be more pronounced in the age group
      25-34 years. The case detection rate of tuberculosis in those aged 15-54 years
      was 125/100,000 people per year. The population attributable risk was 36/100,000
      people per year, implying that 29% of tuberculosis cases at present may be
      attributable to HIV-1 infection. It is concluded that HIV-1 infection is a major
      contributing factor to the increased case detection rate of tuberculosis observed
      over the past 10 years in Mwanza Region. If the prevalence of HIV-1 continues to
      increase, the incidence of tuberculosis will continue to rise as well.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8144301
TI  - Caretaker recognition of respiratory signs in children: correlation with physical
      examination findings, x-ray diagnosis and pulse oximetry.
AB  - Caretaker recognition of clinical utility of respiratory signs and symptoms in
      the prediction of pneumonia was examined in a prospective study of infants and
      children in four cities in Egypt. In all 688 children aged 2 months-5 years
      presenting with a history and/or physical examination findings of cough and
      difficult or fast breathing were recruited from out-patient health facilities.
      The validity of caretaker terms was determined using paediatrician observation of
      standard respiratory signs and symptoms, x-ray diagnosis and pulse oximetry as
      standards. The sensitivity of 'nahagan' (Egyptian Arabic for fast breathing) for
      identifying elevated respiratory rate was 78% +/- 4, and was slightly higher for
      < 12 month olds (85% +/- 5) versus children aged 1-5 years (74% +/- 5). 'Sedro
      tale nazel', which describes the chest as moving up and down, was a sensitive
      (86% +/- 3) and specific (60% +/- 4) indicator of chest indrawing. 'Tazyeek'
      (wheeze) had a sensitivity of 75% +/- 3 and specificity of 66% +/- 4 when
      compared to paediatrician assessment of wheezing during physical examination.
      Although not specific, the caretaker terms, 'nahagan' or 'nafas seria' (fast
      breathing) and 'sedro tale nazel' (chest indrawing), either spontaneously or
      after asking, were sensitive (> 71%) indicators of radiologic pneumonia and
      oxygen desaturation, and therefore can be used to prompt timely health seeking
      behaviour in these settings.

PMID- 8144303
TI  - Q fever: prevalence of antibodies to Coxiella burnetii in the Basque country.
AB  - The aim of this study was to ascertain the prevalence of Coxiella burnetii
      infection in the Basque population. To this end a stratified sampling was carried
      out taking as a criterion the size of the population in a given area of
      residence. Residents in sparsely populated areas were found to have a prevalence
      of 38.5%, significantly greater than in highly populated areas (odds ratio [OR] =
      1.56; 95% confidence interval [CI]: 1.08-2.27 and OR = 1.58; 95% CI: 1.09-2.30).
      The prevalence was significantly higher in males (36.3%) than in females (29%),
      and was found to increase significantly with age. Current or previous
      participation in activities relating to agriculture and/or livestock farming or
      even having contact with cattle, goats or sheep were also found to be risk
      factors for the infection. A fuller study of the determinants of chronic Q fever
      should be initiated.

PMID- 8144302
TI  - Risk factors for mortality from acute lower respiratory tract infections in young
      Gambian children.
AB  - A case-control study has been undertaken in a rural area of The Gambia to
      evaluate risk factors for death from acute lower respiratory tract infections
      (ALRI) in young children. On the basis of a post-mortem interview 129 children
      aged < 2 years were thought to have died from ALRI. These cases were each matched
      according to age, sex, ethnic group, time and place of death with a child who had
      died from a cause other than an ALRI and with two live control children. Cases
      and controls were well matched. Comparison of cases and live controls suggested
      that exposure to smoke during cooking, parental smoking and exclusive, prolonged
      breastfeeding were associated with an increased risk of death from ALRI whilst
      sharing a bed with siblings, use of antenatal and welfare clinics and
      immunization were associated with a reduced risk of death from ALRI. No
      associations were found between mortality from ALRI and maternal education and
      literacy, socioeconomic status or with the age of the mother. Comparison of
      children who died from causes other than ALRI with the live controls showed a
      similar pattern of associations and no significant differences were found in any
      of the risk factors studied between children whose deaths were attributed to ALRI
      and those whose death was attributed to another cause. Association of death with
      exposure to smoke during cooking was the strongest risk factor identified. This
      risk might be altered by reducing smoke exposure during cooking.

PMID- 8144304
TI  - What does the odds ratio estimate in a case-control study?
AB  - The use of the term 'odds ratio' in reporting the findings of case-control
      studies is technically correct, but is often misleading. The meaning of the odds
      ratio estimates obtained in a case-control study differs according to whether
      controls are selected from person-time at risk (the study base), persons at risk
      (the base-population at risk at the beginning of follow-up), or survivors (the
      population at risk at the end of follow-up). These three methods of control
      selection correspond to estimating the rate ratio, risk ratio, or the odds ratio
      respectively, by means of calculating the odds ratio in the subjects actually
      studied. None of these estimation procedures depends on any rare disease
      assumption. Where the rare disease assumption is relevant is whether the effect
      which is estimated (e.g. the odds ratio) is approximately equal to some other
      effect measure of interest (e.g. the risk ratio or rate ratio) in the underlying
      study base. To avoid confusion on this issue, authors should be encouraged to not
      only specify the manner in which controls have been selected (e.g. by density
      sampling) but also the corresponding effect measure which is being estimated
      (e.g. the rate ratio) by the 'odds ratio' which is obtained in a case-control
      analysis.

PMID- 8144305
TI  - Spatial correlation in ecological analysis.
AB  - This paper presents a statistical approach, originally developed for mapping
      disease risk, to ecological regression analysis in the presence of spatial
      autocorrelated extra-Poisson variation. An insight into the effect of allowing
      for spatial autocorrelation on the relationship between disease rates and
      explanatory variables is given. Examples based on cancer frequency in Scotland
      and Sardinia are used to illustrate the interpretation of regression coefficient
      and further methodological issues.

PMID- 8144306
TI  - Cancer mortality and electric transmission equipment.

PMID- 8144307
TI  - Risk factors for drug overdose mortality.

PMID- 8144308
TI  - Occupation and cancers of the lung and bladder: a case-control study in Bombay.

PMID- 8144309
TI  - Mortality in a rural South African mission, 1837-1909: an historical cohort study
      using church records.
AB  - Three decadal birth cohorts (1837-1846), 1870-1879 and 1900-1909) each of
      approximately 500 individuals, were constructed retrospectively through the
      parish records of the Moravian Mission at Mamre in the Western Cape region of
      South Africa. Nominative data collection techniques were used to determine the
      infant mortality rates (IMR), quinquennial mortality rates (QMR) and life
      expectancies of the three cohorts. The quality of the data was investigated,
      specifically non-registration and attrition. Overall, male registration coverage
      was substantially better than that for females. Birth registration was best for
      the 1837-1846 cohort for males and females, with the 1900-1909 registration being
      next best. Infant death registration was most complete for males in these two
      cohorts, but was poor for females. Based on these data, the IMR for the cohorts
      born in 1837-1846, 1870-1879 and 1900-1909 (196, 182 and 128 per 1000
      respectively for males and 160, 172 and 97 per 1000 respectively for females)
      appeared to be underestimates. There was some evidence of a downward trend for
      the IMR with time for males, but this was not statistically significant. For the
      three cohorts QMR did not differ statistically for males, but for females the
      third cohort was consistently lower than the other cohorts. The difference was
      small (well within the 95% confidence interval) but the third cohort ranked
      consistently below the other two. The life expectancies did not differ
      significantly between cohorts. The life expectancies at birth (range 34-40 years
      for males and 32-45 years for females) were probably overestimates due to biased
      IMR. The life expectancies at age 1 (range 41-44 for males and 37-49 for females)
      were considered to be more representative figures. Life expectancies at age 20
      (37-45 years) were fairly stable over time except for females in the 1900-1909
      cohort whose life expectancies were substantially higher than the figures for the
      earlier cohorts. All mortality indices investigated in this study consistently
      showed a lighter burden of mortality in historical Mamre compared to 'coloureds'
      in the Cape Colony at the turn of the century. This is probably the result of the
      better housing, environmental, social, economic and educational conditions on the
      missions relative to the rest of the Colony in the century after the emancipation
      of slaves.

PMID- 8144310
TI  - Cancer incidence among 78,000 asthmatic patients.
AB  - The risk of cancer was evaluated among 77,952 asthma patients with bronchial
      asthma. The series was obtained through linkage of two registers: the Finnish
      Social Insurance Institution's file of asthma patients and the Finnish Cancer
      Registry. There was a significant excess risk of lung cancer in both sexes, the
      standardized incidence ratio (SIR) being 1.32 among men and 1.66 among women. In
      women, the risk of cancer of the rectum was significantly increased (SIR 1.42),
      whereas the risks of cancer of the corpus uteri and multiple myeloma were lower
      than expected (SIR 0.76 and 0.53, respectively). In men, the incidence of cancer
      of the larynx was significantly reduced (SIR 0.63) and that of the bladder
      increased (SIR 1.25). When both sexes were combined, cancers of the colon (SIR
      1.17) and rectum (SIR 1.28) also showed a significantly elevated risk. A
      reduction in risk was seen in stomach cancer (SIR 0.88) and lymphatic leukaemia
      (SIR 0.55). The increased lung cancer risk may be due to local inflammatory
      changes. It is possible that differences in the immune system, e.g. natural
      killer cell activity, explain some of the reduced cancer risks.

PMID- 8144311
TI  - Nutrient intake and gastric cancer risk: a case-control study in Spain.
AB  - A case-control study of dietary factors and gastric cancer was conducted between
      September 1986 and March 1989 in the Barcelona metropolitan area, Spain. In all
      117 cases with histologically confirmed diagnosis of gastric adenocarcinoma were
      matched on sex, age and possession of a telephone to 234 population controls. Of
      the controls 188 (80.3%) were selected by random digit telephone dialing and 46
      (19.7%) by neighbourhood of residence. Information about frequency and amount of
      consumption of 89 alimentary items was gathered by questionnaire, and cases and
      controls were interviewed in their homes by trained interviewers. The gastric
      cancer risk decreased in proportion to vitamin C intake. In multivariate analysis
      adjusting for major covariables, energy and vitamin A intake, the estimated odds
      ratio (OR) for the upper quartile of vitamin C intake was 0.3 (95% confidence
      interval [CI]: 0.1-0.8). After adjustment for major covariables, calories and
      vitamin C intake, vitamin A did not show significant association with the gastric
      cancer risk. Our findings are consistent with previous case-control studies and
      with the hypothesis that vitamin C may inhibit the intragastric nitrosation
      process.

PMID- 8144313
TI  - Acemetacin and indomethacin: differential inhibition of constitutive and
      inducible cyclo-oxygenases in human gastric mucosa and leucocytes.
AB  - Cyclo-oxygenase, a key enzyme in prostaglandin production, is mainly in the
      constitutive form (COX-1) in gastric mucosa, whereas leucocytes have an inducible
      enzyme (COX-2). We report that indomethacin and its glycolic acid ester
      acemetacin have quantitatively different effects on prostanoid synthesis in these
      tissues. Human gastric mucosa (fresh operation specimens, cut finely and washed),
      and 1-1.5 x 10(6) human blood leucocytes stimulated with lipopolysaccharide (5
      micrograms/ml), were incubated with acemetacin or indomethacin (0.1, 1, 10, 100
      micrograms/ml). Eicosanoids in the medium were measured by radioimmunoassay
      (RIA). In leucocytes, acemetacin and indomethacin were more potent cyclo
      oxygenase inhibitors than in the gastric mucosa, and both reduced the PGE levels
      to similar extents (70-98% and 72-100% respectively, n = 5). LTB4 was reduced
      only at 100 micrograms/ml of either drug. In gastric mucosal incubates,
      acemetacin was less potent than indomethacin in causing a concentration-related
      inhibition of PGE accumulation (19-74% vs 34-84%; n = 6, p < 0.05). Acemetacin
      was also less potent than indomethacin in reducing gastric 6-keto-PGF1 alpha and
      TXB2 (by 11-79% vs 45-72%, and 0-80% vs 29-80% respectively, p < 0.05). The
      finding that acemetacin is equipotent to indomethacin on leucocyte cyclo
      oxygenase (inducible enzyme, COX-2) but less active on the gastric mucosa (COX-1)
      is consistent with an effective analgesic and anti-inflammatory activity of
      acemetacin coupled with better gastric tolerance than that to indomethacin.

PMID- 8144312
TI  - Nutritional profile of women with fibrocystic breast disease.
AB  - The relationship between nutritional factors including eating habits and the
      presence or absence of fibrocystic breast disease (FBD) with regard to other
      known risk factors has been investigated in women participating in the National
      Breast Screening Study (NBSS) in Montreal, Canada. Included in this case-control
      study were 334 patients with FBD aged 40-59 years at entry to NBSS and 340
      controls. Personal and family history was collected from medical records and by
      interview conducted by a research nurse. Nutritional assessment was done by 24
      hour dietary recall, by a food frequency questionnaire and by identification of
      changes in eating habits 5 years prior to diagnosis. Women > or = 50 years with
      FBD had higher intake of energy, carbohydrate, fibre, vitamin D, free folacin,
      calcium, sodium, potassium and magnesium but lower intake of cholesterol than
      controls. In women < 50 years body mass index and lower protein, niacin and zinc
      intake, were associated with FBD. In logistic regression analysis, breast pain
      and education > 12 years were among the most important predictive variables for
      FBD. The use of oral contraceptives, cholesterol intake > or = 300 mg/day, the
      proportion of energy provided by fat and saturated fatty acid intake above 10% of
      energy had a protective effect. The comparison of FBD patients diagnosed by
      biopsy and those by clinical examination indicated that increasing age had a
      significant association with the risk of biopsy and a rather weak association
      with the percentage of energy supplied by fat.

PMID- 8144314
TI  - Similarities and differences between the interleukin-1 induction and action
      pathways in human macrophages.
AB  - Cyclic AMP, protein kinase A and NF kappa B have been implicated as second
      messengers in the interleukin-1 (IL-1) action pathway. Since IL-1 induces more IL
      1 release, the IL-1 action pathway may share some common second messengers with
      the IL-1 induction pathway. Therefore, we investigated whether cyclic AMP,
      protein kinase A and NF kappa B are involved in the induction of IL-1 beta
      release by human peripheral blood monocyte-derived macrophages (HPBM) stimulated
      with a specific IL-1 beta inducer, 9-hydroxyoctadecadienoic acid (9-HODE). With
      regard to cyclic AMP, it peaked 30 min after 9-HODE stimulation. A role for
      cyclic AMP in IL-1 beta induction was suggested since forskolin was sufficient to
      induce IL-1 beta release from HPBM. 9-HODE stimulation of HPBM also activated an
      early peak of protein kinase A activity. A requirement of protein kinase A in IL
      1 beta induction was suggested since 9-HODE-induced IL-1 beta release was
      inhibited with a selective protein kinase A inhibitor, Rp-isomer (IC50:5 microM).
      Lastly, to examine the role of NF kappa B, incubation of HPBM with a double
      stranded oligodeoxyribonucleotide (ds-oligo) bearing the NF kappa B consensus
      sequence produced a dose-dependent enhancement of 9-HODE-induced IL-1 beta
      release, whereas a ds-oligo containing an unrelated Oct-1 motif had no effect.
      These results suggest that NF kappa B plays a negative role in the IL-1 beta
      induction pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144315
TI  - Inhibition of neutrophil function in vitro by heparan sulfate.
AB  - The profibrinolytic and antithrombotic glycosaminoglycan heparan sulfate (HS) was
      tested in vitro on some neutrophil functions induced by several stimuli. HS 1-500
      micrograms/ml was able to significantly inhibit, in a dose-dependent fashion,
      superoxide anion generation, lysozyme and beta-glucuronidase release from
      neutrophils stimulated with the formylated oligopeptide fMLP, the ionophore
      A23187, and Platelet Activating Factor. Such an effect could represent an
      additional therapeutical benefit in those pathological conditions in which
      neutrophil activation contributes to tissue injury and vascular damage.

PMID- 8144316
TI  - Heparan sulfate fractions: pharmacological properties and effect on smooth muscle
      cell proliferation in vitro.
AB  - In this study we have evaluated the effect of heparan sulfate fractions with
      different molecular weights on the growth of aortic smooth muscle cells (SMC) of
      rat in vitro. These fractions were obtained from unfractionated heparan sulfate
      by a gel filtration technique. The fraction having a molecular weight of 25.5 kDa
      showed a significant antiproliferative activity only at higher concentrations,
      while the fractions with molecular weight ranging from 10.7 kDa to 6.8 kDa were
      effective in reducing cell proliferation at very low concentrations (10(-5) nM
      and 10(-4) nM). The dose-effect curves are characterized by an initial plateau
      followed by an increase in effectiveness at the highest concentration. The
      relationship between molecular weight and antiproliferative activity is
      discussed.

PMID- 8144317
TI  - Ischaemia and reperfusion-induced injury in rat retina obtained from normotensive
      and spontaneously hypertensive rats: effects of free radical scavengers.
AB  - The authors have studied the effects of free radical scavengers, superoxide
      dismutase (SOD) and extract of Ginkgo biloba (EGb 761, flavone-rich extract) on
      ion shifts (Na, K and Ca) induced by ischaemia and reperfusion in rat retina
      obtained from normotensive and spontaneously hypertensive rats. Eyes were
      subjected to 90 min of ischaemia by occlusion of the retinal artery, followed by
      4 and 24 hours of reperfusion. SOD (15,000 U/kg, i.v.) or EGb 761 (50 mg/kg, per
      os) was administered in a daily dose for 10 days. In the drug-free control
      groups, 90 min of ischaemia significantly increased tissue Na gains from their
      pre-ischaemic control values of 63 +/- 7 microM/g dry weight (in retina obtained
      from normotensive rats) and 76 microM/g dry weight (in retina obtained from
      hypertensive rats) to 89 +/- 9 microM/g dry weight and 101 +/- 7 microM/g dry
      weight, respectively. During reperfusion, a further elevation was found in
      retinal Na in both the normotensive and hypertensive groups. Probably, because of
      the ischaemia-induced inhibition of Na-K-ATPase, retinal K loss was detected
      after ischaemia and reperfusion, respectively. An accumulation of retinal Ca was
      measured after ischaemia and reperfusion in the normotensive and spontaneously
      hypertensive groups. Both free radical scavengers significantly reduced the
      maldistribution of ions induced by ischaemia and reperfusion, but the
      effectiveness of drugs was more evident in normotensive than hypertensive
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144318
TI  - [The epidemiology of pain].

PMID- 8144319
TI  - [Pain therapy in chronic headache and migraine].

PMID- 8144320
TI  - [Pain therapy of acute and chronic spinal cord diseases].

PMID- 8144321
TI  - [Therapeutic pain centers. Pain clinic--ambulatory pain management--general
      practice in pain therapy].

PMID- 8144322
TI  - [Eosinophilic fasciitis (Shulman syndrome). Differential diagnosis of chronic
      eosinophilia-myalgia syndrome after L-tryptophan administration].

PMID- 8144323
TI  - [43-year-old patient with fever, pharyngitis and polyarthralgia].

PMID- 8144324
TI  - [15th Congress of the European Society of Cardiology].

PMID- 8144325
TI  - [Position of the German Society of Internal Medicine on the "Recommendations for
      the curriculum of medical education by the Expert Committee on the Topic of
      Reorganization of Medical Education" by the Federal Health Office 12 November
      1992].

PMID- 8144326
TI  - [Comments on the contribution by M. Stille-Siegener et al. Myocarditis].

PMID- 8144327
TI  - [Roentgen findings in heart diseases].

PMID- 8144328
TI  - Funding opportunities for young investigators in radiology.

PMID- 8144329
TI  - A survey of radiology clerkships at teaching hospitals in the United States.
AB  - RATIONALE AND OBJECTIVES: The nature and extent of medical school radiology
      clerkships were qualified. METHODS: Questionnaires were sent to 126 medical
      school radiology departments in the United States. Queries were made regarding
      length and requirements for clerkships, methods of teaching, methods of student
      evaluation, and responsibility for these functions. RESULTS: Fifty-seven
      responses (45%) were received. Methods of student teaching varied, but most
      departments relied on readout sessions, watching procedures, "show-and-tell"
      sessions, didactic slide and film presentations, and various other methods.
      Emphasis of most student clerkships was placed on teaching imaging disease
      processes rather than on how to read x-rays. A written examination was most
      commonly used to evaluate student performance. Most teaching was done by full
      time faculty, with lesser contributions from part-time faculty, fellows, and
      residents. CONCLUSIONS: The nature and extent of medical school radiology
      clerkships in departments responding to the survey varied, but most conformed, at
      least in part, to standards based on survey results and the published literature.

PMID- 8144330
TI  - Trends in European radiologic education in 1993.

PMID- 8144331
TI  - Child with intractable seizures and cranial asymmetry.

PMID- 8144332
TI  - Fractal analysis of renal cortical perfusion.
AB  - RATIONALE AND OBJECTIVES: Contrast-enhanced computed tomography (CT) images of
      canine renal cortex were analyzed to determine if the heterogeneous pixel
      intensity patterns met the requirements for fractal analysis and if the
      heterogeneity could be quantified by a fractal dimension, Df. METHODS: Contrast
      enhanced CT images were obtained after injection of iodipamide ethyl ester (IDE),
      a vascular marker, or iohexol, a freely filtered interstitial marker, into the
      catheterized renal artery of an anesthetized dog. Images were mounted on a
      graphics workstation for analysis. A computer program was written to determine
      the fractal dimension of the pixel-intensity pattern within selected regions.
      RESULTS: All regions of renal cortex examined met the requirements for fractal
      analysis. Three seconds after injection of IDE, the mean fractal dimension
      decreased significantly from 1.21 +/- 0.05 to 1.12 +/- 0.06 (P < .05). Although
      the mean fractal dimensions were not significantly different, the variation in
      the fractal dimension around the renal cortex was significantly different with
      IDE as compared with iohexol at 3 seconds (P < .05). Differences in the change in
      fractal dimension over time were also observed with IDE as compared with iohexol.
      CONCLUSIONS: Fractal dimension measurement provides a new means to examine the in
      vivo organization of renal vascular perfusion by quantifying pixel heterogeneity
      in contrast-enhanced CT. This may prove useful in understanding and quantifying
      the pathophysiologic changes in renal disease.

PMID- 8144333
TI  - Measurement of lactate in acutely ischemic rat kidneys using magnetic resonance
      spectroscopy.
AB  - RATIONALE AND OBJECTIVES: Quantification of lactate in the kidney by 1H magnetic
      resonance spectroscopy (MRS) is a difficult task because of the presence of large
      amounts of peri-renal fat. When an editing scheme is used to detect lactate that
      filters out all resonances except lactate, there is no suitable metabolite to
      serve as an internal standard. In this study, the authors evaluate the potential
      of MRS to measure the absolute lactate concentration in rat kidneys during acute
      ischemia using MRS. MATERIALS AND METHODS: The authors propose a method based on
      a double resonance lactate editing scheme used in combination with the fully
      relaxed water peak as an internal standard. Experiments were performed on the
      left kidney rendered ischemic in eight rats. RESULTS: Renal lactate
      concentrations measured by MRS were compared with values derived from chemical
      analysis. The mean (+/- standard deviation) renal lactate concentrations measured
      by MRS and determined chemically were 12 +/- 1.2 umol/g, and 12.94 +/- 1.07
      umol/g wet weight, respectively. The coefficient of variation for paired
      observations was 2.96%, indicating excellent agreement between the two methods
      used for measuring lactate. DISCUSSION: The study results demonstrate that it is
      possible to assess the lactate concentration in a rat model of ischemic kidney
      with MRS and suggest that the total lactate pool is detectable by this method
      under these experimental conditions.

PMID- 8144334
TI  - Comparison of angiographic opacification of ioxaglate and iodixanol by digital
      region-of-interest processing technique in an experimental circulation model.
AB  - RATIONALE AND OBJECTIVES: By using digital ROI (region of interest) processing
      techniques, we measured and compared directly the angiographic opacification of
      ioxaglate and iodixanol in an experimental circulation model. METHODS: A
      pulsatile pump circulated water into a 2-mm plastic tube for digital subtraction
      angiography (DSA). Altogether, 90 digital imaging series were registered during
      injections of two contrast media with 320, 300, and 270 mg/mL iodine
      concentrations. By selecting a "vessel" ROI and a subtracted background ROI, a
      time-density curve (TDC) was created. From the TDC, the average density of
      contrast media and the appearance time of contrast media into the selected ROI
      were measured. RESULTS: The average density was statistically different (P < .01)
      among three various iodine concentrations of the contrast media, but no
      difference was found between the two contrast media. The appearance times of
      ioxaglate with 320 mg/mL iodine concentration were statistically shorter (P <
      .01) than those of iodixanol. In both contrast medium groups, the appearance
      times were statistically shorter (P < .05) with 270 mg/mL iodine concentration
      than with two higher iodine concentrations. CONCLUSION: The current experimental
      set-up facilitates reproducible measurement of angiographic opacification during
      the injection of contrast media. The average densities between ioxaglate and
      iodixanol are the same, but are significantly different among three iodine
      concentrations. The different appearance times of the two CM and the three iodine
      concentrations may be caused by the various viscosities of the contrast media.

PMID- 8144335
TI  - Magnetic resonance imaging of bone marrow changes after irradiation.
AB  - RATIONALE AND OBJECTIVES: Signal changes of irradiated bone marrow are thought to
      represent fatty change. However, more recent studies have indicated that other
      factors may contribute to these signal changes. We performed animal studies to
      investigate magnetic resonance (MR) signal change factors in correlation with
      histologic findings. MATERIALS AND METHODS: Forty-two male Wistar rats were given
      single doses (3, 8, and 20 Gy) of irradiation. Magnetic resonance imaging (1.5 T)
      was performed using spin-echo technique. RESULTS: In the acute phase (days 1-3),
      the T1 time was prolonged, probably secondary to decreased cellularity and edema.
      After this phase, the irradiated marrow showed marked T1 and T2 shortening that
      correlated with hemorrhage. In the chronic phase (after day 10), fatty
      replacement, fibrosis, and regeneration were observed. T2 times were stable in
      spite of regeneration because of the susceptibility effect of hemosiderin.
      CONCLUSION: The MR signal changes of irradiated marrow reflect not only fatty
      replacement, but hemorrhage as well.

PMID- 8144336
TI  - Subjective evaluations of mammographic accreditation phantom images by three
      observer groups.
AB  - RATIONALE AND OBJECTIVES: Mammography providers are under increasing pressure to
      become certified by the American College of Radiology (ACR). Successful
      accreditation is contingent on passing a phantom image quality test. This study
      was undertaken to evaluate viewer performance with the phantom image evaluation
      process and to determine any observer group differences. METHODS: A series of
      standard phantom images were viewed by 30 medical physicists, 30 diagnostic
      radiologists, and 30 inexperienced observers. From the responses, object
      detection rates and passing rates according to the ACR criteria were established.
      These responses were analyzed with standard nonparametric tests to assess the
      degree of variability, correlation, and agreement among different observer
      groups. RESULTS: Median passing scores were similar for the radiologists and
      untrained readers, but the medical physicists appear to differ from the other two
      groups. There was not sufficient evidence to indicate that special training among
      physicists made a significant difference in median passing scores or mass
      detection rates. However, such training appeared to significantly affect the
      detection of microcalcification and fibril test patterns among the physicists'
      subgroups. Agreement among observer groups was high for all groups, but tended to
      be lower for overall passing rates than for any of the individual test objects.
      Agreement among physicists was affected by their subspecialty, presumably caused
      by their levels of specific training for these visual tasks. CONCLUSIONS: The
      authors conclude that choosing medical physicists to evaluate mammographic
      phantom films appears to be a good choice among potential observer groups, and
      that special training for reading these images affects their detection abilities
      and consistency. However, because passing rates did not appear to be affected by
      special training and given the current rapid degree of change in this area, more
      testing of medical physicists is desirable to examine these effects over time,
      and to study the effect of developing standards for training.

PMID- 8144337
TI  - The practice of chest radiology in departments with residency programs.
AB  - OBJECTIVES: The authors assessed to what extent radiology teaching programs
      employed dedicated chest radiologists and their functions. METHODS: Information
      regarding the clinical, teaching, and research role of the chest radiologist was
      available from responses to a survey of radiology departments with residency
      training programs in the United States and Canada. Emphasis was placed on the
      role of chest subspecialists, "dedicated chest radiologists" (DCRs), who spent at
      least two thirds of their clinical time interpreting and directing chest-related
      imaging studies and procedures. RESULTS: Among the 171 residency programs that
      responded, 118 had DCRs. There were 262 full-time and 233 part-time DCR
      positions, of which 43 were not filled. Among departments with DCRs, 66% were
      medical school programs while the remaining 34% were independent or medical
      school-affiliated programs; 30% were organized by organ system, 5% by technology,
      and 65% had a combination of both; and 78% had more than 12 residents. DCRs
      interpreted routine chest radiographs in 96%, critical care radiographs in 94%,
      chest computed tomography (CT) studies in 72%, and chest magnetic resonance
      imaging (MRI) studies in 44% of their departments. Departments without DCRs were
      usually smaller, 70% having 12 or fewer residents. Their designated chest
      radiologists interpreted all chest radiographs in 21%, all critical care
      radiographs in 19%, all chest CT studies in 13% and all chest MRI studies in 8%
      of these departments. CONCLUSIONS: Dedicated chest radiologists were more
      involved than non-DCRs in all aspects of chest imaging, teaching, and research
      including analysis of image quality and acquisition of new technology. The
      highest quality of chest radiology training, defined as programs in which the
      chest fellowship positions were filled in 1991, was found in departments in which
      DCRs interpreted all chest radiographs, all chest CT studies, and most MRI
      studies.

PMID- 8144338
TI  - Effect of noise on the detection of rib fractures by residents.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the effect of noise on the
      detectability of rib fractures by residents. METHODS: Eight radiology residents
      read chest posterior-anterior radiographs of 92 subjects with rib fracture(s) and
      28 normal subjects to detect rib fracture(s) according to a five-point scale of
      confidence, under quiet and "noisy" conditions. Each individual's attitude toward
      noise was measured by a multiple-choice questionnaire. RESULTS: The readers were
      divided into two groups depending on the questionnaire result: group A readers
      were accustomed to a quiet environment, and group B readers were accustomed to
      noisy environments or were unaffected by noise. Group A's performance, measured
      by the area (Az) under the receiver operating characteristic (ROC) curve, was
      better in quiet conditions when compared with their performance in noisy
      conditions; however, the opposite tendency was observed for group B. There was a
      significant individual difference of performance in response to noise.
      CONCLUSION: Effect of noise on the detection of rib fractures depends on an
      individual's attitude toward sound and noise.

PMID- 8144339
TI  - Dosimetric consequences of radiopharmaceutical infiltrations.
AB  - RATIONALE AND OBJECTIVES: Little is known about the time-related biologic
      behavior of radiopharmaceutical misinjections. Such inadvertent tissue
      infiltration of such injections may not only adversely affect a scheduled test or
      cause some discomfort, but potentially could produce tissue damage.
      Radiopharmaceutical infiltrations were assessed in a rat model. METHODS:
      Particulate and nonparticulate radiopharmaceuticals were injected subcutaneously
      or intradermally into an anesthetized shaved rat model. The rate of release of
      the nine infiltrations per radiopharmaceutical per injection type were measured
      from computer data acquired with a gamma camera up to 24 hours after
      administration. These data were used for dosimetry determinations. RESULTS: When
      injected subcutaneously, the particulate radiopharmaceutical, technetium 99m
      (99mTc) albumin microspheres, exhibited essentially no movement, and the soluble
      agents showed a biexponential release pattern. The rate of release was similar
      for 99mTc methylene diphosphonate (99mTc MDP) and for 67Ga citrate (67Ga),
      whereas thallous chloride (201Tl) exhibited the slowest release pattern. The
      average effective half-lives (T1/2 av-eff) were 78.3 minutes, 76.1 minutes, and
      268.4 minutes, respectively. When injected intradermally, the nonparticulates
      exhibited a triexponential release pattern; MDP showed a more rapid release (T1/2
      av-eff, 50 minutes) and 201Tl showed the slowest (T1/2 av-eff, 491.2 minutes).
      Absorbed doses were calculated using conventional medical internal radiation dose
      (MIRD) methodology for small unit density spheres. The absorbed dose was greatest
      for a 201Tl infiltration. A 201Tl infiltrate of 1 mCi per gm of tissue is capable
      of producing radiation-absorbed doses greater than 500 rads. Additional studies
      were performed with heat, hyaluronidase, and volume dilution in an attempt to
      accelerate the rate of release of 201Tl. Local heat application proved to be more
      efficient than volume change or hyaluronidase application. CONCLUSION: These data
      indicate an insignificant skin radiation burden from the majority of
      nonparticulate infiltrated radiodiagnostic agents. Thallium 201, however, has the
      potential to produce significant radiation burdens when infiltrated at high
      specific activity. Actual human infiltration release rates may differ because of
      variants in blood flow and assumed infiltration volume relative to the animal
      model.

PMID- 8144340
TI  - The effect of radiographic contrast media on leukocyte motility.
AB  - RATIONALE AND OBJECTIVES: Studies describing the effects of radiographic contrast
      media (RCM) in leukocyte chemotaxis have been contradictory. No studies have been
      performed after in-vivo exposure. The authors assess the effect of RCM on
      leukocytes following in-vivo exposure. METHODS: Seventeen patients were studied
      after intraarterial bolus injection of 75 mL of iohexol (300 mg/mL) or iotrolan
      (300 mg/mL), 30 minutes and 24 hours postinjection; chemotaxis was assessed using
      an ex-vivo whole-blood under-agarose method. RESULTS: With iohexol, there was a
      profound reduction in chemotaxis compared with the preinjection state (P = .001)
      at 30 minutes. No effect, however, was seen at 24 hours. With iotrolan, no
      significant reduction in chemotaxis was seen at 30 minutes or at 24 hours.
      CONCLUSIONS: Radiographic contrast media have differing effects on leukocyte
      chemotaxis. This may be of significance in the selection of appropriate RCM in
      certain patients.

PMID- 8144341
TI  - Effect of radiographic contrast media on granulocyte phagocytosis of Escherichia
      coli in a whole blood flow cytometric assay.
AB  - RATIONALE AND OBJECTIVES: Earlier studies have demonstrated an adverse effect of
      radiographic contrast media (CM) on granulocyte phagocytosis. Most studies in the
      past have depended on granulocyte separative procedures that may themselves
      affect granulocyte functions. This study was performed to evaluate the effect of
      CM on phagocytosis using a flow cytometric assay allowing more physiological
      assay conditions. METHODS: Twenty consecutive patients were blindly randomized to
      receive the nonionic ratio 3.0 CM iohexol or the ionic ratio 3.0 CM ioxaglate for
      intravenous urography. Granulocyte phagocytic potential was measured before and
      at 1, 5, and 20 minutes after CM administration with a flow cytometric whole
      blood method evaluating the ingestion of complement- and immunoglobulin G (IgG)
      opsonized fluorescent Escherichia Coli bacteria. RESULTS: The ability of
      granulocytes to phagocytize opsonized E. Coli was adversely affected by both CM
      used. Compared with baseline values, significantly decreased phagocytic activity
      was observed for iohexol at 1, 5, and 20 minutes and for ioxaglate at 1 and 5
      minutes. The largest decrease with ioxaglate was from 85.3 +/- 10.5 to 69.3 +/-
      16.3 (5 minutes), and the largest change with iohexol was from 87.1 +/- 8.5 to
      74.5 +/- 15.9 (5 minutes). CONCLUSION: These results confirm earlier reports that
      ionic and nonionic CM adversely affect the phagocytic ability of granulocytes
      after intravenous administration.

PMID- 8144342
TI  - Physicochemical parameters of x-ray contrast media.
AB  - RATIONALE AND OBJECTIVES: Osmolality, including "dynamic osmolality," which is
      observed during dilution in the plasma, viscosity, density, and partition
      coefficient of 11 commercially available contrast media and two new nonionic
      monomers were determined. METHODS: Osmolality was measured by vapor pressure
      osmometry, viscosity by determining flow in microcapillaries, and partition
      coefficient in n-octanol or n-butanol/water mixtures by inductively coupled
      plasma mass spectroscopy or x-ray fluorescence analysis of iodine concentrations.
      RESULTS: For the commercially available contrast media, the following
      statistically significant ranking of osmolality was obtained at 300 mg iodine/mL:
      iotrolan << ioxaglate < iopromide < iopamidol < ioversol = iohexol < iopentol <<
      meglumine diatrizoate. The novel nonionic monomers, ZK 119095 and ZK 139129, had
      very low osmolalities, and ZK 139129 was isotonic to blood. The partition
      coefficient for the system n-octanol/water was lowest for the ionic compounds
      ioxaglate and diatrizoate followed by the nonionic dimer iotrolan. In n-butanol,
      iotrolan showed the lowest partition coefficient. CONCLUSION: "Dynamic
      osmolalities" of contrast media may differ from static values possibly because of
      the formation of "quasi-oligomers." Especially for ZK 139129, disaggregation
      occurred during dilution and the osmolality increased slightly. However,
      osmolality was lower than for any other monomer during the whole dilution
      process.

PMID- 8144343
TI  - Optimization of an oral magnetic particle formulation as a gastrointestinal
      contrast agent for magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: Magnetically susceptible iron oxide (MSIO) contrast
      agents for magnetic resonance imaging (MRI) of the gastrointestinal (GI) tract
      are limited because they produce magnetic susceptibility artifacts. To determine
      whether oral magnetic particles (WIN 39996) can be an effective MRI contrast
      agent without producing induced image artifacts, we optimized a liquid
      formulation of WIN 39996. METHODS: A range of concentrations (25-250 micrograms
      iron/mL) and viscosities (1-600 cP) was imaged in a phantom at 1.5 T using
      conventional spin-echo and gradient-recalled echo pulse sequences. Some
      formulations also contained titanium. RESULTS: All concentrations of WIN 39996 at
      1 cP produced susceptibility artifacts. For formulations in the 150 to 600 cP
      range, the 125 to 150 micrograms/mL concentrations produced signal blackening and
      magnetic susceptibility image distortion comparable to an air control.
      Concentrations greater than 150 micrograms/mL were unacceptable because they
      produced significant susceptibility artifacts, while concentrations less than 125
      micrograms/mL were undesirable because they produced insufficient signal
      blackening. CONCLUSIONS: These preliminary in-vitro studies suggest that an
      optimized liquid formulation of WIN 39996 can be produced that yields excellent
      negative contrast without producing image artifacts.

PMID- 8144344
TI  - Diagnostic performance of magnetic resonance imaging for the diagnosis of rotator
      cuff tears using supplemental images in the oblique sagittal plane.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the diagnostic utility of
      supplemental imaging in the oblique sagittal (OS) plane for the magnetic
      resonance imaging (MRI) diagnosis of rotator cuff tears. METHODS: Two
      radiologists with varying levels of MRI experience blindly reviewed shoulder MR
      examinations of 50 patients for rotator cuff tears. Shoulder examinations were
      interpreted twice, initially using only double-echo spin-echo images obtained in
      the oblique coronal (OC) plane and later using double-echo spin-echo images
      obtained in the both the OC and OS planes. Tears were characterized according to
      size, location, and extent, and levels of diagnostic confidence were evaluated.
      RESULTS: Sensitivity and specificity of MR for the diagnosis of rotator cuff tear
      was 85% and 80%, respectively, with the OC series increasing to 95% and 93%,
      respectively with OCOS scans. However, these increases were not statistically
      significant. Receiver operating characteristic (ROC) curves suggest a trend
      toward increased diagnostic confidence when supplemental OS scans are available,
      especially for the less experienced reader. Characterization of rotator cuff
      tears was not improved with additional OS images. CONCLUSIONS: Supplemental OS
      scans did not demonstrate a definite improvement in diagnostic accuracy for
      rotator cuff tears compared to OC scans alone. Estimations based on sample size
      calculations indicate that a much larger population of patients would be needed
      to show a statistically significant difference.

PMID- 8144345
TI  - Contrast-enhanced magnetic resonance imaging of the breast.

PMID- 8144346
TI  - Cell cycle and growth regulation in RAS2 mutant cells of Saccharomyces
      cerevisiae.
AB  - Yeast cells carrying ras2 temperature-sensitive mutations undergo a specific
      arrest in the prereplicative unbudded phase of the cell cycle when they are
      shifted to non-permissive temperatures. At 36.5 degrees C, in spite of their
      abnormally large cell size, bulk protein synthesis and accumulation rates are
      depressed in ras2 temperature-sensitive cells in comparison with isogenic wild
      type. At the same temperature, total RNA synthesis and accumulation rates are
      much more inhibited, suggesting that a defective Ras2/cAMP pathway alters the
      coordination between RNA and protein synthesis rates. The preferential RNA
      synthesis inhibition is correlated to a specific inhibition of the synthesis of
      the 35S rRNA precursor. These findings, taken together with the results of
      previous analyses, are in favour of a control by the cAMP pathway on rRNA
      biosynthesis.

PMID- 8144347
TI  - Persistent postoperative ventricular tachycardia treatment by using external
      cardiopulmonary support.
AB  - Drug-resistant incessant ventricular tachycardia (DRIVT) after cardiac surgery is
      a rare but almost always fatal event. Antiarrhythmic therapy seems to be
      ineffective and electrical cardioversion is of limited value when these patients
      present themselves with recurrent, sustained ventricular tachycardia. A patient
      with DRIVT in whom external cardiopulmonary support finally succeeded in bringing
      about resuscitation will be described in this article. The use of external
      cardiopulmonary support (CPS) should be considered in patients with this kind of
      malignant arrhythmia.

PMID- 8144348
TI  - Retinopathy of prematurity: incidence and severity in Hawaii.
AB  - Because survival of low birth-weight infants requiring intensive care has
      improved recently, particularly since the advent of exogenous surfactant therapy,
      we reviewed our experience at Kapiolani Medical Center for Women and Children
      (KMCWC) from 1989 to 1991 to determine if the incidence of retinopathy of
      prematurity (ROP), a serious long-term complication, had also increased. During
      this 3-year period, threshold disease, the ROP stage in which cryosurgery is
      recommended, occurred only in infants < or = 1000 grams. Seventy-four infants <
      or = 1000 grams were diagnosed with ROP of any stage. Sixteen eyes (9 infants)
      reached threshold; 14 were treated with cryosurgery. Six of these eyes have
      useful vision on follow up; 8 do not. Exogenous surfactant therapy had no
      significant effect on ROP incidence or severity in our series. Although ROP
      incidence did not increase during this review period, it remains a serious
      problem in high-risk premature infants in our Newborn Intensive Care Unit.

PMID- 8144349
TI  - Ethnic differences in the recurrence of adenomatous polyps after colonoscopic
      polypectomy.
AB  - A retrospective study was done of polyp recurrence rates following an initial
      clearing colonoscopy for adenomatous polyps. The intent of the study was to
      identify risk factors that would predict a greater risk for recurrence in
      Hawaii's ethnically diverse population. When the initial exam detected multiple
      polyps, a higher recurrence rate was found in Caucasian patients.

PMID- 8144350
TI  - Blood transfusion: the risks and benefits.
AB  - As greater attention is focused on medical and legal risks of the transfusion
      process, physicians ordering a blood transfusion must advise their patients
      thoroughly and clearly of the potential risks involved. Physicians must explain
      clearly to patients that a zero-risk blood supply is impossible to achieve;
      patients must understand that all necessary steps practicable have been taken to
      ensure the safest possible supply.

PMID- 8144351
TI  - Hb Sinai-Baltimore or alpha 2 beta (2)18(A15)Val->Gly, a silent, mildly unstable
      beta chain variant detected by isoelectrofocusing and high performance liquid
      chromatography.
AB  - Isoelectrofocusing and high performance liquid chromatographic methods were used
      to study an abnormal hemoglobin present in a Black male infant and his mother.
      The variant, named Hb Sinai-Baltimore, focused slightly behind Hb A and separated
      incompletely from Hb A by cation exchange high performance liquid chromatography,
      while the separation of the beta A and beta X chains by reversed phase high
      performance liquid chromatography was complete. The variant was identified
      through an analysis of peptides in a tryptic digest of the isolated beta X chain
      and by sequencing of amplified DNA which included the beta-globin gene. The Val
      >Gly replacement at position beta 18 (codon 18; GTG->GGG) or at the last position
      of the A helix decreases the stability of the variant without affecting the
      hematological parameters of its carrier. The propositus was a compound
      heterozygote for Hb Sinai-Baltimore and Hb S; the relative quantities of the two
      variant chains were somewhat different from those of the beta X and beta A chains
      in the mother with the simple Hb Sinai-Baltimore heterozygosity. An uncertainty
      about the alpha-globin gene status in the child prevented a further evaluation of
      these differences.

PMID- 8144352
TI  - Hb Howick [beta 37(C3)Trp-->Gly]: a new high oxygen affinity variant of the alpha
      1 beta 2 contact.
AB  - Hb Howick or beta 37(C3) Trp-->Gly is a newly described hemoglobin variant found
      in an adult male. Hematological data and stability by the isopropanol stability
      test were normal. The abnormal variant comprised 29% of total hemoglobin and
      migrated in the Hb D position on cellulose acetate at pH 8.6, and in the Hb F
      position on citrate agar (pH 6.0). Oxygen dissociation studies on the whole blood
      showed the variant to have a higher oxygen affinity than normal, with a P50 of
      19.8 mm Hg (normal, 26 mm Hg). There were also significant differences in the
      saturation curve. The variant showed a reduced Bohr effect which was manifested
      as very high oxygen affinity at low pH and saturation. The beta 37 residue is an
      alpha 1 beta 2 contact site and the substitution of the tryptophan for a glycine
      would be expected to result in a destabilization of the deoxy-hemoglobin form
      because of the reduced number of hydrogen bonds, salt bridges and van der Waal
      contacts between the alpha 1 and beta 2 chains.

PMID- 8144353
TI  - The beta-thalassemia frameshift at codon 8 (-AA) observed in four Chinese of the
      Uygur nationality.
AB  - During a survey for beta-thalassemia in Kashi City, Xinjiang Province, P.R.
      China, four unrelated Uygur students were identified as heterozygotes for the
      beta-thalassemia frameshift at codon 8 (-AA). Detection was with the polymerase
      chain reaction combined with allele-specific oligonucleotide hybridization. This
      beta-thalassemia allele has not been observed in the Chinese population before
      and might be rather specific for the Uygur nationality.

PMID- 8144354
TI  - Hb San Diego [beta 109(G11)Val-->Met] in an Iranian: further evidence for a
      mutational hot spot at position 109 of the beta-globin gene.

PMID- 8144355
TI  - Hb F-Saskatoon or alpha 2G gamma (2)21(B3)Glu-->Lys observed in a North American
      Indian newborn.

PMID- 8144356
TI  - A novel 13 Bp deletion in the 3'UTR of the beta-globin gene causes beta
      thalassemia in a Turkish patient.

PMID- 8144357
TI  - A novel initiation codon mutation (ATG-->ATT) in a beta-thalassemia patient.

PMID- 8144358
TI  - A novel beta-thalassemia mutation [IVS-II-5 (G-->C)] in a Chinese family from
      Guangxi Province, P.R. China.

PMID- 8144359
TI  - Analysis of the gonadal sex of five intersex pigs using Y chromosomal markers.
AB  - DNA isolated from gonadal tissue of five intersex pigs was analyzed for the
      presence of the Y chromosomal markers ZFY and DYZ1. Four cases showed no
      detectable male-specific DNA-sequences. The fifth case exhibited a weak male
      specific band at Southern blot analysis with the human ZFY probe and showed a
      male-specific PCR-product with DYZ1 primers, indicating an XX/XY gonadal chimera.

PMID- 8144360
TI  - Position-effect variegation and z1 mediated white repression in the In(1)wis
      system in Drosophila melanogaster.
AB  - We have characterized a new X-chromosomal inversion in Drosophila melanogaster,
      extending from just distal of white to just proximal of the bb locus. The
      inversion places the w-isoxanthopterinless (wis) allele close to heterochromatin
      and under the influence of position-effect variegation (PEV). The wis gene
      activity is also regulated by chromosome pairing-dependent z1-mediated
      repression. By changing the environment, using specific second site modifiers,
      altering the amount of heterochromatin, and disturbing the chromosome pairing, we
      have been able to separately affect the two regulatory phenomena and analyse
      their respective impact on the wis regulation. We provide evidence that under
      normal conditions PEV and z1 mediated white repression are additive. However, at
      extreme levels of wis repression by PEV, changes in the z1-mediated interactions
      are not observable. This indicates that PEV is epistatic to z1-mediated
      regulation of wis. We also show that deficiencies in the short arm of Y act as
      suppressors of the z1-mediated white repression. This suppression does not
      influence PEV and is thus not due to the lower amount of heterochromatin. We
      propose that nonhomologous chromosome pairing between X and Y is important for
      the synapsis-dependent z1-mediated repression of white transcription activity in
      this system.

PMID- 8144361
TI  - Frequency and distribution of rob (1;29) in three Portuguese cattle breeds.
AB  - Representative samples of Portuguese cattle from Barrosa, Maronesa, and Mirandesa
      breeds underwent cytogenetic investigation. Banding showed that 134 (65.0%)
      Barrosas, 74 (40.2%) Maronesas and 4 (1.6%) Mirandesas carried rob (1;29). The
      frequency of this translocation in the three breeds (39% in Barrosas, 23% in
      Maronesas, and 1% in Mirandesas) was in a genetic Hardy-Weinberg equilibrium for
      the three karyological forms (2n = 60, 2n = 59 and 2n = 58), strongly supporting
      the hypothesis for an ancient origin of this translocation and the hypothesis of
      the origin of Maronesas from Barrosa and Mirandesa cross-breeding.

PMID- 8144362
TI  - A new centric fusion translocation in cattle, rob(16;18).
AB  - A Barrosa bull (Portugal) has been found to carry a new Robertsonian
      translocation involving chromosomes 16 and 18 of standard cattle karyotype, as
      demonstrated by GBG- and RBG-banding techniques. C-banding patterns revealed the
      dicentric nature of this translocation. A comparison between normal cattle
      chromosome 16 and the q-arms of translocation chromosome and river buffalo
      chromosome 5 revealed the same G- and R-banding patterns, with only exception of
      a pericentromeric G-positive band which has been lost in river buffalo 5q and
      conserved in normal cattle chromosome 16 and rob(16;18) q-arms.

PMID- 8144363
TI  - Mapping of glutathione transferase (GST) genes in the rat.
AB  - Glutathione transferases (GST) make up a large group of related enzymes in
      mammalian tissues. The enzyme molecules are dimeric and at least 13 different
      subunits occur in the rat. Each subunit appears to be coded for by a distinct
      gene, and thus there is a large GST gene family in the rat. Recently, there have
      been several reports of the mapping of rat GST genes. In the present
      communication we confirm the previous assignments and extend the data with the
      mapping to rat chromosome 2 of a previously unmapped GST gene (Gstm1), and with
      the regional mapping of seven Gstp genes. These mappings provide further evidence
      for conservation of syntenic gene relationships among mammals. The human homologs
      of Gstm1 map to chromosome 1, and belong to a group of 9 genes that show
      conserved synteny on rat chromosome 2. The corresponding murine genes in most
      cases map to mouse chromosome 3. Similarly, the human homolog of Gstp maps to
      chromosome 11, and is one of 10 genes that exhibit conserved synteny on rat
      chromosome 1. The corresponding mouse genes map to mouse chromosome 7. Previously
      only one gene on rat chromosome 8 had a human homolog on chromosome 6, and rat
      Gsta1 is the second instance. Based on these mappings it appears that a new group
      of genes will exhibit conserved synteny on rat chromosome 8, human chromosome 6
      and mouse chromosome 9. Interestingly, each of the three groups of conserved
      synteny seems to span the region across the centromeres of the human chromosomes.

PMID- 8144364
TI  - Expression of an endopolygalacturonase gene during growth and abscission of peach
      fruits.

PMID- 8144365
TI  - Irradiation: knowledge leads to support.

PMID- 8144366
TI  - Irradiation found to kill harmful bacteria in beef.

PMID- 8144367
TI  - USDA inspection system scrutinized by congressional leader.

PMID- 8144368
TI  - USDA continues push for safe handling labels.

PMID- 8144370
TI  - Czech swine producers capitalize on window of opportunity.

PMID- 8144369
TI  - Compendium of animal rabies control, 1994. National Association of State Public
      Health Veterinarians, Inc.

PMID- 8144371
TI  - Clarification on earlier letters regarding animal rights.

PMID- 8144372
TI  - Communication skills in veterinary education.

PMID- 8144373
TI  - Sins of veterinary marketing.

PMID- 8144374
TI  - A retrospective on 35 years in the animal health industry.

PMID- 8144375
TI  - Why teach production medicine to veterinary students?

PMID- 8144376
TI  - The human side of veterinary medicine. How are you managing change?

PMID- 8144377
TI  - Clinical approach to control of bovine paratuberculosis.

PMID- 8144378
TI  - What is your diagnosis? Bone tumor of the proximal portion of the humerus in a
      dog.

PMID- 8144379
TI  - Septicemic listeriosis, thrombocytopenia, blood parasitism, and hepatopathy in a
      llama.

PMID- 8144380
TI  - Employment of 1993 male and female graduates of US veterinary medical colleges.

PMID- 8144381
TI  - Is your hospital really safe?

PMID- 8144382
TI  - Intralesional implant for treatment of primary oral malignant melanoma in dogs.
AB  - The feasibility, safety, and efficacy of a new method of local, sustained-release
      chemotherapy by use of intralesional cisplatin implants were evaluated in the
      treatment of oral malignant melanoma. The implant is an injectable viscous gel
      composed of a protein carrier matrix, a vasoactive modifier, and a
      chemotherapeutic drug. Twenty dogs with biopsy-proven melanomas were treated at 1
      to 2-week intervals by injection with cisplatin implant. Tumors were treated
      until they resolved or were judged to be unresponsive. In 3 dogs with tumors
      unresponsive to cisplatin implants, methotrexate implants were used, and in 2 of
      these dogs, carmustine implants followed the methotrexate. Tumor responses were
      evaluated by sequential measurements. Melanomas in 14 (70%) of 20 dogs had a >
      50% decrease in volume, and in 11 (55%) of these dogs, had a complete response.
      Tumors with complete responses received a mean cisplatin dose of 11.7 +/- 1.8 mg,
      delivered in a mean of 2.6 treatments. Two of the dogs with complete response
      also were treated with methotrexate and carmustine. Implants were well tolerated.
      Local necrosis, limited to the treatment site, developed in most tumors (17/20)
      and was associated with tumor response. Systemic toxicosis was minimal; renal
      insufficiency after cisplatin implants was not evident. Median survival times of
      dogs with complete tumor response (51 weeks) was substantially greater than that
      of dogs without local tumor control (10.5 weeks). Recursive partitioning analysis
      of variables indicated that mandibular tumors of short duration were associated
      with a positive outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144383
TI  - Receiver operating characteristic curve analysis of the performance of various
      radiographic protocols when screening dogs for pulmonary metastases.
AB  - Five radiographic protocols for detecting pulmonary metastases in dogs were
      compared by analyzing receiver operating characteristic curves for the protocols.
      Protocols compared were a right lateral view only, a left lateral view only,
      right lateral and dorsoventral views, both lateral views, and all 3 views. Three
      radiologists used each of the protocols to evaluate 99 sets of thoracic
      radiographs. Fifty-two sets of radiographs were from dogs confirmed
      histologically to have pulmonary metastases and 47 were from dogs proven at
      necropsy to be free of pulmonary metastases. Results of the 5 protocols were not
      statistically different. We concluded that a third view is not necessary when
      routinely screening dogs with cancer for pulmonary metastases and that the
      standard 2-view thoracic examination should be adequate. However, in individual
      cases, a third view may be the determining factor in establishing a radiographic
      diagnosis and should be obtained if any suspicious areas are seen.

PMID- 8144384
TI  - Globule leukocyte tumor involving the small intestine in a cat.
AB  - Globule leukocyte tumor involving the distal portion of the jejunum and proximal
      portion of the ileum caused chronic vomiting and weight loss in a 3-year-old cat.
      The intestinal mass was resected during exploratory laparotomy. The histologic
      appearance of the mass was characterized by inclusion of numerous
      intracytoplasmic eosinophilic granules. Similar cells were found in the
      mesenteric lymph node and were suggestive of metastasis. Tumor recurrence was not
      detected until 13.5 months after the surgery. The malignant but slow-growing
      nature of this tumor allowed a disease-free interval that exceeded 1 year,
      despite incomplete tumor resection.

PMID- 8144385
TI  - Effect of oxytetracycline on metacarpophalangeal and distal interphalangeal joint
      angles in newborn foals.
AB  - Thirty-five newborn foals were assigned to 1 of 3 groups and treated with 0.9%
      NaCl solution (saline; group 1; n = 12), oxytetracycline (44 mg/kg of body
      weight; group 2; n = 12), or 2-pyrrolidone (oxytetracycline vehicle; group 3; n =
      11) in saline solution during the first 36 hours after birth. Serum biochemical
      analyses were performed on samples obtained from group-1 and group-2 foals before
      treatment and 24 and 96 hours after treatment. Lateral to medial radiographic
      views of the forelimbs were obtained before treatment and 24 and 96 hours after
      treatment in all foals. Metacarpophalangeal and distal interphalangeal joint
      angles were measured from the radiographic images. Significant changes in blood
      chemistry values, other than those typically observed in newborn foals, were not
      detected. A significant decrease in mean metacarpophalangeal joint angle was
      observed in foals 24 hours after treatment with oxytetracycline, compared with
      that in foals of groups 1 and 3. The mean metacarpophalangeal joint angle
      returned to pretreatment values by 96 hours. Oxytetracycline appears to be an
      effective method for obtaining a short-term moderate decrease in
      metacarpophalangeal joint angle in newborn foals.

PMID- 8144386
TI  - Prevalence and factors associated with development of laminitis in horses with
      duodenitis/proximal jejunitis: 33 cases (1985-1991).
AB  - Medical records of 116 horses admitted to the Texas Veterinary Medical Center
      between Jan 1, 1984 and Dec 31, 1991 with duodenitis/proximal jejunitis (DPJ)
      were reviewed. The prevalence of laminitis was 28.4% (33/116; 95% confidence
      interval: 20.2 to 36.6%). The prevalence of DPJ and DPJ-associated laminitis did
      not appear to vary significantly by year during the study period. Anamnesis,
      physical examination, clinicopathologic data, and initial treatment recorded at
      the time of admission were reviewed to determine risk factors associated with
      development of laminitis associated with DPJ. A trend of increasing prevalence of
      laminitis with increasing weight was observed. Using a multiple logistic
      regression model, horses weighting > or = 550 kg were approximately twice as
      likely to develop laminitis than horses weighting < 550 kg (P = 0.048). Horses
      with hemorrhagic reflux observed at the time of admission were nearly twice as
      likely to develop laminitis than horses without hemorrhagic reflux (P = 0.022).
      Treatments administered prior to admission or at our clinic did not significantly
      affect development of laminitis, except for administration of heparin to prevent
      laminitis. Of 33 horses that developed laminitis associated with DPJ, 2 had
      laminitis at the time of admission. These 2 horses were excluded from analysis of
      the effects of heparin administered as prophylaxis for laminitis; neither horse
      was treated with heparin. The proportion of horses that developed laminitis among
      horses that received heparin (0.0%; 0/12) was significantly (P = 0.018) less than
      that among horses that did not receive heparin (29.8%; 31/104).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8144387
TI  - Comparison of microbiologic culture, an enzyme-linked immunosorbent assay, and
      determination of somatic cell count for diagnosing Staphylococcus aureus mastitis
      in dairy cows.
AB  - Results of using microbiologic culture of a single milk sample, determination of
      somatic cell count (SCC), an ELISA, and a combination of determination of SCC and
      ELISA to diagnose Staphylococcus aureus mastitis in dairy cattle were compared.
      Cows were considered to have S aureus intramammary infections if microbiologic
      culture of at least 2 of 3 consecutive sets of milk samples yielded growth of the
      organism. Data were analyzed from milk samples collected over a 4-month period
      from 185 cows in 5 herds. Sensitivity, specificity, and likelihood ratio of a
      positive test result for microbiologic culture of a single milk sample were 93%,
      99%, and 93.0, respectively. Sensitivity, specificity, and likelihood ratio of a
      positive test result for ELISA were 69%, 61%, and 1.8, respectively, and for
      determination of SCC, they were 79%, 72%, and 2.9, respectively. Combination of
      determination of SCC and ELISA had sensitivity, specificity, and likelihood ratio
      of a positive test result of 80%, 62%, and 3.4, respectively. Results from
      microbiologic culture of consecutive milk samples were more consistent than
      results of ELISA performed on consecutive samples. These data suggest that
      microbiologic culture of a single milk sample is the best of the 3 tests studied
      for diagnosing S aureus intramammary infection.

PMID- 8144388
TI  - Infertility associated with Eperythrozoon wenyonii infection in a bull.
AB  - A 16-month-old Charolais bull was examined because of acute onset of scrotal and
      hind limb edema, fever, tachycardia, tachypnea, anorexia, and lethargy. Scrotal
      circumference on initial examination was 48 cm. Clinicopathologic abnormalities
      included microcytic, normochromic anemia and numerous Eperythrozoon organisms in
      blood smears. Results of immunohistochemical staining of a skin biopsy specimen
      suggested that the edema was the result of an Arthus-type reaction. Semen quality
      deteriorated rapidly, and the bull was aspermic within 7 days. The bull was
      treated with oxytetracycline, and the anemia and edema gradually subsided.
      Eperythrozoon organisms were not detected in blood smears after 3 days. Six
      months after initial examination, results of physical examination and semen
      evaluation were normal. We hypothesize that scrotal edema caused failure of
      testicular thermoregulation, resulting in transient production of abnormal sperm
      and infertility.

PMID- 8144389
TI  - Rochalimaea henselae infections: newly recognized zoonoses transmitted by
      domestic cats.

PMID- 8144390
TI  - Nucleotide excision repair genes involved in xeroderma pigmentosum.

PMID- 8144391
TI  - Detection of guanine-C8-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine adduct as
      a single spot on thin-layer chromatography by modification of the 32P
      postlabeling method.
AB  - N-(Deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8
      PhIP) has been shown to be a major adduct in DNA of rats given [3H]PhIP. However,
      when DNA from organs of rats fed PhIP was analyzed by the 32P-postlabeling method
      under standard and adduct-intensification conditions, four adduct spots were
      observed, and 3',5'-pdGp-C8-PhIP was detected as a minor, not a major, adduct
      spot. Since the three other major adduct spots were suspected to be those of
      adducted di- or oligo-nucleotides, the 32P-labeled samples were further treated
      with nuclease P1 and phosphodiesterase I and found to yield only a single adduct
      spot. The material in this adduct spot was confirmed to be 5'-pdG-C8-PhIP. Thus,
      using this newly modified 32P-postlabeling method, dG-C8-PhIP was detected as a
      major adduct in DNA of rats given PhIP.

PMID- 8144392
TI  - Expression of cripto in human pancreatic tumors.
AB  - The expression of cripto gene product was examined immunohistochemically in 45
      surgically resected pancreatic tumors, including 32 invasive ductal carcinomas, 4
      intraductal papillary adenocarcinomas, 4 intraductal papillary adenomas, 2
      mucinous cystadenomas, 2 islet cell tumors, and one solid and cystic tumor, and
      compared with that in 32 areas of accompanying chronic pancreatitis present in
      the cases of invasive ductal carcinomas and 5 non-tumorous areas of pancreas
      without pancreatitis. All pancreatic ductal tumors including adenomas and
      carcinomas showed positive staining with no difference in terms of staining
      intensity among intraductal tumors and invasive carcinomas with or without mucin
      hypersecretion. Islet cell tumors were positively stained but the solid and
      cystic tumor was negative. Duct epithelial cells and acinar cells were negative
      but islet cells were positive in the pancreas tissues without pancreatitis. Cells
      arranged in duct-like structures in areas of accompanying chronic pancreatitis
      were positively stained. The results suggest that cripto expression might be
      associated with a growth advantage of tumor cells and also with differentiation
      to form duct-like structures.

PMID- 8144393
TI  - Increased expression of trk proto-oncogene by gamma-interferon in human
      neuroblastoma cell lines.
AB  - Three human neuroblastoma cell lines were examined to determine the effect of
      recombinant gamma-interferon (IFN-gamma) treatment on the expression of trk proto
      oncogene. Increased levels of trk proto-oncogene mRNA were observed in two
      neuroblastoma cell lines (KP-N-RT and KP-N-SI(FA)) after IFN-gamma treatment. The
      levels of trk mRNA increased with growth inhibition and morphological change in a
      time- and dose-dependent manner. The decreased level of N-myc mRNA after IFN
      gamma treatment in KP-N-RT was inversely correlated with trk mRNA. Our results
      suggest that IFN-gamma can modulate the signal transduction of nerve growth
      factor in human neuroblastoma cells.

PMID- 8144394
TI  - Circumvention of atypical multidrug resistance with tumor necrosis factor.
AB  - Some "multidrug-resistant" (MDR) cell lines are not associated with a defect in
      drug accumulation or with the overexpression of P-glycoprotein. These cell lines
      are defined as "atypical MDR" (at-MDR) and they often express altered or mutated
      topoisomerase II. We investigated the ability of tumor necrosis factor to reverse
      at-MDR (in the human ovarian cancer cell line A2780 DX3) on the basis of its
      efficacy in potentiating in vitro topoisomerase II-targeted drugs, and because
      there is convincing evidence that the synergy is due to an increased number of
      topoisomerase-associated strand-breaks as well as to an increased level of
      extractable topoisomerase.

PMID- 8144395
TI  - Incidence of childhood cancer in Osaka, Japan, 1971-1988: reclassification of
      registered cases by Birch's scheme using information on clinical diagnosis,
      histology and primary site.
AB  - In 1971-1988, 4,021 malignant tumors occurring among children under 15 years of
      age were registered in the Osaka Cancer Registry, a population-based registry
      which covers Osaka Prefecture, Japan. These patients were reclassified into 12
      diagnostic groups by Birch's scheme using information on clinical diagnosis,
      histology and primary site. The annual age-standardized incidence rate for
      childhood cancer per million children was 130.3 for males and 104.9 for females
      in 1971-88. Comparing the incidence rates for both sexes in 1981-88 with those in
      1971-80 in Osaka, we observed a significant decrease of acute non-lymphocytic
      leukemia (ANLL) and a significant increase of all cancers, acute lymphocytic
      leukemia, non-Hodgkin lymphoma, sympathetic nervous system tumors, soft-tissue
      sarcomas, and gonadal and germ-cell tumors. Age-standardized incidence rates in
      around 1971-80 of the above-mentioned diagnostic groups were compared among 4
      population-based registries; Osaka, Miyagi (Japan), SEER (U.S.), and the National
      Registry of Childhood Tumors (England and Wales). Rates for ANLL and gonadal and
      germ-cell tumors were higher and those for other diagnostic groups were lower in
      Osaka, especially for Hodgkin's disease. Thus, in 1980-88 in Osaka, rates for
      Hodgkin's disease remained low and rates for gonadal and germ-cell tumors
      increased, though rates for other cancers appeared to resemble the levels in
      caucasian populations. The incidence of childhood cancer in Japan was estimated
      according to the diagnostic groups in Birch's scheme.

PMID- 8144396
TI  - Lower incidence of K-ras codon 12 mutation in flat colorectal adenomas than in
      polypoid adenomas.
AB  - In order to clarify genetic changes in flat adenomas, K-ras codon 12 point
      mutations were examined in 56 flat adenomas, 81 polypoid adenomas and 42 cancers
      of colon and rectum. The mutation frequency in flat adenomas was 23% (13/56),
      significantly lower than that in polypoid adenomas (67%: 54/81) and cancers (76%:
      32/42). Even mildly dysplastic adenomas or small (less than 5 mm) adenomas showed
      higher mutation incidence in polypoid type (62%, 57%) than in flat type (23%,
      19%). Among flat adenomas, flat elevated lesions exhibited relatively higher
      mutation frequency than completely flat or depressed ones. As for cancers, 14
      tumors (33%) contained mutations only in a minor tumor cell population,
      indicating that these mutations occur at a late stage of tumorigenesis. These
      results suggest that the adenoma-carcinoma sequence through flat adenomas may be
      different from that through polypoid adenomas, and genetic changes may be
      heterogeneous in colorectal carcinogenesis.

PMID- 8144398
TI  - In vivo efficacy of neocarzinostatin coupled with Fab human/mouse chimeric
      monoclonal antibody A7 against human colorectal cancer.
AB  - The anticancer polypeptide neocarzinostatin (NCS) was covalently coupled to a
      human/mouse chimeric Fab A7 monoclonal antibody (chFabA7) and the in vivo
      efficacy of this conjugate was examined. NCS concentration assay was carried out,
      and acute toxicity and tumoricidal effects were examined. The concentration
      assay, using anti-NCS monoclonal antibody, revealed that administration of the
      chA7Fab conjugate leads to a greater blood retention and a higher tumor
      accumulation of NCS, when compared to free NCS administration. The tumoricidal
      effect of chA7Fab-NCS was higher than that of either free NCS or the saline
      control, against antigen-positive tumors. In antigen-negative tumors there was no
      difference in toxic effect among the three preparations. Values of LD50,
      reflecting acute toxicity, were 5050 U/kg and 3600 U/kg for the chA7Fab-NCS and
      the free NCS, respectively. These results suggest that chFabA7-NCS may be a
      promising tool for targeting cancer chemotherapy.

PMID- 8144397
TI  - Regulation of gelatinase production in metastatic renal cell carcinoma by organ
      specific fibroblasts.
AB  - We have recently established a human renal cell carcinoma KG-2 line that is
      tumorigenic in the subcutis (ectopic) and kidney (orthotopic) of nude mice but
      spontaneously metastasizes to the lung only after orthotopic implantation. KG-2
      cells growing in the kidney (orthotopic) and lung metastases secreted higher
      levels of gelatinase than did cells growing in the subcutis (ectopic). We
      examined whether organ-specific fibroblasts play a role in the regulation of
      gelatinase production and invasion by renal carcinoma cells. The gelatinase level
      in the culture supernatants of KG-2 cells was increased by their cultivation with
      mouse kidney or lung fibroblasts. In contrast, cocultivation of KG-2 cells with
      mouse skin fibroblasts resulted in a significant reduction of gelatinase
      activity. Similar results were obtained by culturing KG-2 cells in the media
      conditioned by the different mouse fibroblasts. We, therefore, investigated
      effects on KG-2 cells of cytokines and growth factors known to be produced by
      fibroblasts of various origins. Of ten cytokines and growth factors tested, basic
      fibroblast growth factor, hepatocyte growth factor, and transforming growth
      factor-beta 1 (TGF-beta 1) stimulated gelatinase expression by the cultured KG-2
      cells. Parallel immunohistochemical analyses revealed that mouse kidney and lung
      fibroblasts produced higher levels of TGF-beta 1 than did skin fibroblasts. These
      results indicate that gelatinase production by KG-2 renal cell carcinoma cells is
      influenced by the organ microenvironment. Specifically, organ-specific
      fibroblasts regulate the production of degradative enzymes by KG-2 cells and,
      hence, profoundly influence their invasive and metastatic capacity.

PMID- 8144399
TI  - Autonomous expressions of cytokine genes by human lung cancer cells and their
      paracrine regulation.
AB  - Cell-to-cell interaction between tumors and host inflammatory cells is important
      for the subsequent cancer progression or regression. We examined the expressions
      of mRNAs for various proinflammatory cytokines by nine human lung cancer cell
      lines and the influences of cytokines on their gene expressions. The cytokines
      used were interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis
      factor alpha (TNF-alpha), granulocyte-macrophage colony stimulating factor (GM
      CSF) and monocyte chemotactic and activating factor. Gene expressions of
      cytokines were measured by Northern blot analysis. Substantial expressions of
      cytokine genes were detected in several lung cancer cell lines such as RERF-LC
      MS, RERF-LC-OK and VMRC-LCD, although the levels of expression of each cytokine
      varied in different cell lines. Four lung cancer cell lines (RERF-LC-MS, RERF-LC
      OK, A549 and YO-88) were used to examine the effects of exogenous cytokines (IL-1
      beta, TNF-alpha and GM-CSF) on cytokine gene expressions by the cells. TNF-alpha
      and IL-1 beta caused significant changes in the levels of mRNA expressions of
      certain cytokines. Moreover, on stimulation with TNF-alpha, RERF-LC-OK cells
      produced IL-6 extracellularly. These extensive differences in the levels of gene
      expressions and productions of cytokines could have profound effects on the
      interactions between human lung cancer cells and the corresponding host cells.

PMID- 8144401
TI  - Flow cytometric detection of proliferative cells in leukemias.
AB  - We studied the proliferative activity of leukemic cells obtained from the
      peripheral blood and bone marrow of 34 patients; 30 with acute leukemia and 4
      with chronic myelogenous leukemia in blastic crisis. Flow cytometry was performed
      using monoclonal antibody against DNA polymerase alpha. Since fresh and frozen
      cells showed virtually identical DNA polymerase alpha-positive populations and
      flow cytometric histograms, 52 cryopreserved samples (25 from peripheral blood
      and 27 from bone marrow) were used in this study. The DNA polymerase alpha
      positive population ranged from 20.4% to 84.7% in peripheral blood, and from 6.5%
      to 92.1% in bone marrow. A positive correlation (r = 0.76, P < 0.01) was found
      between DNA polymerase alpha-positive populations in peripheral blood and bone
      marrow from the same patient. This suggests that the DNA polymerase alpha
      positive population in the bone marrow can be estimated from that in peripheral
      blood. No relationship was observed between the positive population and the
      response to chemotherapy. Statistical analyses for all cases showed no
      relationship between the DNA polymerase alpha-positive population and either the
      tumor cell count or time to reach a nadir. However, a negative correlation was
      observed between the positive population in bone marrow samples and the time to
      reach a nadir (r = -0.64, P < 0.05) in those patients who achieved a complete
      response. In addition, in the cases of acute non-lymphocytic leukemia who did not
      respond to chemotherapy, a positive correlation was observed between the tumor
      cell count in bone marrow and the DNA polymerase alpha-positive population (r =
      0.93, P < 0.01). Thus, the method described here provides a simple and time
      efficient means of detecting the proliferative activity of leukemic cells, which
      is a useful parameter in the treatment of leukemia.

PMID- 8144400
TI  - Different modes of cell-killing action between DNA topoisomerase I and II
      inhibitors revealed by kinetic analysis.
AB  - We compared the modes of cell-killing by DNA topoisomerase I and II inhibitors.
      The effects of camptothecin (CPT), KT-6528 and UCE6 upon colony formation by
      inhibiting DNA topoisomerase I, and of etoposide (VP-16), teniposide, amsacrine
      and UCT4-A as inhibitors of DNA topoisomerase II were analyzed based upon a
      kinetic method that distinguishes between cell cycle phase-specific and 
      nonspecific agents. Human colorectal cancer WiDr cells were exposed to several
      concentrations of each agent for various periods and 90%-inhibitory
      concentrations (IC90) at each time were determined by means of a clonogenic
      assay. When exposure times and corresponding IC90s were plotted on a log-log
      scale, all inhibitors of DNA topoisomerase II gave curves including a linear
      portion with a slope of -1, which is characteristic of cell cycle phase
      nonspecific agents. In contrast, the curves for all inhibitors of DNA
      topoisomerase I had a much steeper slope than -1, which is typical of cell cycle
      phase-specific agents. In agreement with this finding, the cells were remarkably
      accumulated in the G2-M phase when exposed to VP-16, but in late S-phase when
      exposed to CPT as determined by a flow cytometric assay. These results indicated
      that the two classes of agents kill cells in a quite different manner although
      they are inhibitors of similar enzymes.

PMID- 8144402
TI  - A new serum tumor marker, CAM 123-6, highly specific to pulmonary adenocarcinoma.
AB  - KL-6, a circulating mucin-like glycoprotein, is a pulmonary adenocarcinoma
      associated antigen and is also regarded as an indicator of disease activity of
      interstitial pneumonitis. KL-6 has extensive heterogeneous antigenic determinants
      and consists of multiple heterogeneous antigen molecules. We have searched for
      circulating KL-6-associated glycoproteins with superior diagnostic value to KL-6
      as a tumor marker for pulmonary adenocarcinoma. A new murine monoclonal antibody
      EH-123 reacting with an asialosugar chain on KL-6 was established. A new KL-6
      associated molecule detected by a bimonoclonal bideterminant sandwich assay using
      the EH-123 antibody as a catcher and horseradish peroxidase-labeled KL-6 as a
      tracer was designated as CAM 123-6. In 59% (22 of 37) of patients with pulmonary
      adenocarcinoma, serum levels of CAM 123-6 were abnormally elevated and the
      positive rate increased with the progression of clinical stage. Elevated levels
      were not detected in normal individuals or in patients with benign lung diseases,
      other histologic types of lung cancer, gastric cancer, colon cancer or breast
      cancer. CAM 123-6 was more specific to pulmonary adenocarcinoma than
      carcinoembryonic antigen (CEA), but the sensitivity of CAM 123-6 for pulmonary
      adenocarcinoma was similar to that of CEA. CAM 123-6 is a promising candidate as
      a serum tumor marker for pulmonary adenocarcinoma.

PMID- 8144403
TI  - Bactericidal activity in the pig roundworm Ascaris suum.
AB  - A potent, humoral, bactericidal activity against Micrococcus luteus was
      discovered in pseudocoelomic fluid of the pig roundworm, Ascaris suum. The
      activity, which was not bacteriolytic, was not due to lysozyme or to a dietary
      antibiotic. It was not inactivated by exposure to 100 degrees C, to low or high
      pH, or to ethanol. Dialysis, electrophoresis and agar-diffusion experiments
      suggested that the main antibacterial activity in the fluid was associated with a
      basic substance of molecular weight somewhat less than 14,000 Da. Two other Gram
      positive organisms, Bacillus megaterium and Staphylococcus aureus, were also
      killed by the Ascaris fluid, but the Gram-negative Escherichia coli, Proteus
      vulgaris and Bordetella bronchiseptica were insensitive.

PMID- 8144404
TI  - An in-vitro meat model for the immediate bactericidal effect of lactic acid
      decontamination on meat surfaces.
AB  - An in-vitro model of the lactic acid decontamination (LAD) of meat is described.
      As LAD is a disinfection rather than a preservation process the model is based on
      the inactivation kinetics of bacteria in a suspension of pork skin. The model
      takes account of interfering factors present in nature, such as microbial
      interactions, leaching of organic material from the meat surfaces and buffering
      activity.

PMID- 8144405
TI  - Personal recollections of developments in food microbiology.

PMID- 8144406
TI  - Competition between reductive acetogenesis and methanogenesis in the pig large
      intestinal flora.
AB  - Washed bacterial suspensions obtained from the pig hindgut were incubated under
      13CO2 in a buffer containing NaH13CO3 and carbohydrates. Incorporation of 13C
      into short chain fatty acids was assayed by quantitative nuclear magnetic
      resonance. The effects of different levels of H2 added to the gas phase (0, 20
      and 80% v/v) and of the specific methanogenesis inhibitor 2-bromoethane-sulphonic
      acid (BES) were determined. In control incubations increasing the concentration
      of H2 markedly increased methane production. Single- and double-labelled acetate
      and butyrate were formed in all incubations. In the absence of BES, increasing H2
      significantly increased the incorporation of 13CO2 into butyrate and the
      proportion of double-labelled acetate in total labelled acetate. The addition of
      BES proved to be very successful as a methane inhibitor and greatly enhanced the
      amount of mono- and double-labelled acetate, especially at the highest H2 partial
      pressure. The results suggest that methanogenesis inhibited both routes of
      reductive acetogenesis, i.e. the homoacetate fermentation of hexose (represented
      for the most part by single labelling) and the synthesis of acetate from external
      CO2 and H2 (represented mostly by double labelling). A highly significant
      interaction between BES and H2 concentration was observed. At the highest pH2 BES
      increased the proportion of labelled acetate in total acetate from 17.1% for the
      control to 50.9%. It was concluded that although acetogenesis and methanogenesis
      can occur simultaneously in the pig hindgut, reductive acetogenesis may become a
      significant pathway of acetate formation in the absence of methanogenesis.

PMID- 8144407
TI  - The use of impedance for preservative efficacy testing of pharmaceuticals and
      cosmetic products.
AB  - Impedance was investigated for its applicability to preservative efficacy testing
      of pharmaceuticals and cosmetics. A good correlation between impedance detection
      time (Td) and total colony counts (colony-forming units (cfu)) was obtained for
      untreated suspensions of Staphylococcus aureus, Candida albicans, Aspergillus
      niger and Pseudomonas aeruginosa in phosphate-buffered saline (PBS). A good
      correlation between Td and the number of cfu was also obtained for suspensions of
      test organisms treated for varying contact periods with selected concentrations
      of chlorhexidine, methyl paraben and phenoxyethanol in PBS, and methyl paraben in
      cetomacrogol cream, but these correlations were significantly different from
      those for untreated suspensions. It was found that for any given number of cfu
      the Td for preservative treated cells was extended. It is concluded that
      impedance represents a valid method for preservative efficacy testing of
      pharmaceuticals and cosmetics which could be used to achieve more comprehensive
      but economic screening of formulations against a wider range of preservative
      systems and concentrations than is the current approach where only a limited
      range of systems are tested because of the workload involved.

PMID- 8144408
TI  - Detection of toxigenic isolates of Aspergillus flavus and related species on
      coconut cream agar.
AB  - A new readily-prepared medium, coconut cream agar, was developed for the
      detection of aflatoxin production by isolates of Aspergillus flavus and related
      species. Coconut cream agar, which comprised coconut cream (50%) and agar (1.5%),
      detected isolates of A. flavus more effectively than the synthetic media tested
      and was as effective as media containing desiccated coconut. Fluorescence
      colouring of colonies grown on coconut cream agar could be used to differentiate
      A. flavus from A. parasiticus and A. nomius. In addition, conidial colour of A.
      flavus and A. nomius was quite distinct from that of A. parasiticus.

PMID- 8144409
TI  - A set of keys for biochemical identification of environmental Vibrio species.
AB  - A set of biochemical keys which provide fast and presumptive identification for
      Vibrio spp. is presented. They have been specially designed for environmental
      isolates, and can be used for strains that are Gram-negative, give a positive
      oxidase test, grow on TCBS medium and are facultative anaerobes. The keys are
      constituted by 28 tests and a maximum of 10 tests are needed for the most
      complicated identification. They have been designed for routine purposes,
      especially for studies with a high number of isolates. Some tests are included in
      enzyme-activity based kits that could be used with these keys through certain
      results, principally for environmental isolates, should be confirmed by standard
      methods.

PMID- 8144410
TI  - An evaluation of the repeatability and reproducibility of a surface test for the
      activity of disinfectants.
AB  - A collaborative study was carried out to determine the precision of a
      disinfectant surface test method which is currently under consideration for
      development as a harmonized European standard surface test. Results indicate that
      significant variation in microbicidal effect occurs both within and between test
      laboratories despite careful standardization of test conditions, but that the
      variability may be less than that associated with suspension tests. Indications
      are that much of this variability derives from random variations in the
      resistance of the test strains from day to day and, most particularly, from test
      period to test period both within as well as between laboratories. It is
      concluded that although the test may be sufficiently reliable to be used as a
      standard method, adequate replication must be specified to distinguish borderline
      pass from borderline fail concentrations.

PMID- 8144412
TI  - Unmodified and recombinant strains of Lactobacillus plantarum are rapidly lost
      from the rumen by protozoal predation.
AB  - A genetically-manipulated strain of Lactobacillus plantarum and the unmodified
      parent strain were introduced into the rumen of sheep at an initial inoculum
      level of 1 x 10(7) cfu ml-1 of rumen fluid. There were no significant differences
      between the viable counts of the two inoculants throughout a 24 h sampling
      period. The rates of loss were 0.36 and 0.29 h-1 (proportion of colony-forming
      units lost, measured over the first 2 h) for the parent strain and recombinant
      strain respectively, and within 24 h of inoculation neither of the strains were
      detectable in rumen fluid. Further experiments in vitro revealed that the
      inoculants persisted in sterile rumen fluid with a loss rate of 0.044 and 0.057 h
      1 for the parent strain and the recombinant strain respectively. Incubations with
      rumen fluid alone, protozoa-free rumen fluid and protozoa-enriched rumen fluid
      revealed that protozoal predation was the most significant factor in the loss of
      the introduced population. The loss rates from protozoa-free rumen fluid were not
      significantly different (P < 0.05) from those observed in sterile rumen fluid.

PMID- 8144411
TI  - Bacteriological indicators of faecal contamination: result of a loading
      experiment with untreated urban wastewater.
AB  - Some observations were made on the behaviour of total coliforms, faecal
      coliforms, enterococci, numbers of aerobic bacteria, salmonellas and sulphur
      reducing clostridia as bacterial indicators of faecal contamination of
      groundwater. A controlled irrigation experiment was carried out with untreated
      residual water in the alluvial aquifer of the Vega of Granada (Spain). The
      results obtained confirm the value of these parameters are useful indicators of
      very recent faecal contamination; and changes were detected as the level of the
      freatic layer increased and the chemical composition of the groundwater changed.
      These groups of micro-organisms persisted for about 200 h, with the exception of
      the aerobes which survived for much longer. Salmonellas were present at levels
      too low to calculate the extent of faecal contamination and sulphur-reducing
      clostridia were not detected. The results obtained show that irrigation with
      untreated wastewater offers a lower risk of microbiological contamination of
      groundwater compared with the direct addition of waters decanted and/or
      previously filtered.

PMID- 8144413
TI  - Isolation from food sources, of lactic acid bacteria that produced
      antimicrobials.
AB  - The potential of lactic acid bacteria, isolated from a variety of foods, to
      inhibit indicators representative of spoilage and pathogenic bacteria associated
      with food products was examined. Fruit and vegetables were a poor source of
      lactic acid bacteria but large numbers were readily isolated on MRS agar from
      cheese, milk and meat samples. Approximately 1000 isolates from each of the food
      samples were examined by the deferred antagonism procedure to determine their
      ability to inhibit Staphylococcus aureus, Listeria innocua and Pseudomonas fragi.
      Listeria innocua was the bacterium predominantly inhibited by isolates from the
      cheese, milk and meats, but antagonism was also observed to a lesser extent
      against the other indicators. The only inhibition observed for isolates from
      vegetable material was directed against Staph. aureus. The majority of inhibitor
      producers were effective against only one of the indicators but a small number
      were isolated which inhibited two or three.

PMID- 8144414
TI  - Rapid identification using pyrolysis mass spectrometry and artificial neural
      networks of Propionibacterium acnes isolated from dogs.
AB  - Curie-point pyrolysis mass spectra were obtained from reference Propionibacterium
      strains and canine isolates. Artificial neural networks (ANNs) were trained by
      supervised learning (with the back-propagation algorithm) to recognize these
      strains from their pyrolysis mass spectra; all the strains isolated from dogs
      were identified as human wild type P. acnes. This is an important nosological
      discovery, and demonstrates that the combination of pyrolysis mass spectrometry
      and ANNs provides an objective, rapid and accurate identification technique.
      Bacteria isolated from different biopsy specimens from the same dog were found to
      be separate strains of P. acnes, demonstrating a within-animal variation in
      microflora. The classification of the canine isolates by Kohonen artificial
      neural networks (KANNs) was compared with the classical multivariate techniques
      of canonical variates analysis and hierarchical cluster analysis, and found to
      give similar results. This is the first demonstration, within microbiology, of
      KANNs as an unsupervised clustering technique which has the potential to group
      pyrolysis mass spectra both automatically and relatively objectively.

PMID- 8144415
TI  - Antimicrobial activity of shredded carrot extracts on food-borne bacteria and
      yeast.
AB  - Purified ethanolic extracts of peeled and shredded carrots showed an
      antimicrobial effect against a range of food-borne micro-organisms. The minimum
      inhibitory concentration, expressed as mg ml-1 dried carrot material used for the
      extraction were: Leuconostoc mesenteroides, 27; Listeria monocytogenes, > 27 <
      55; Staphylococcus aureus, > 27 < 55; Pseudomonas fluorescens, > 55 < 110;
      Candida lambica, > 55 < 110; Escherichia coli, > 110 < 220. The antimicrobial
      activity was not linked to phenolic compounds but was presumably due to apolar
      components. Free saturated fatty acid (dodecanoic acid) and methyl esters of
      saturated fatty acids (of dodecanoic and pentadecanoic acids) were identified in
      purified active extracts of carrots by gas chromatography coupled to mass
      spectrometry and could be responsible for the antimicrobial activity. This effect
      did not seem to play a role in the resistance of shredded carrots to microbial
      spoilage, although the antimicrobial activity was present in fresh carrots at
      concentrations sufficient to inhibit spoilage bacteria.

PMID- 8144416
TI  - Adaptation of a strain of Spirulina platensis to grow in cobalt- and iodine
      enriched media.
AB  - Cobalt- and iodide-enriched (adapted, tolerant) strains of the protein-rich
      cyanobacterium, Spirulina platensis, were produced by repeated sub-culturing in
      increasing concentrations of the two trace elements. The strains enriched with
      cobalt and iodide showed higher uptake of these elements than the controls. The
      LD50 values for the parent and cobalt-adapted strains were 95 and 231 mumol l-1
      CO2+, respectively. Likewise, the LD50 values for parent and iodide-adapted
      strains were 12 and 42 mmol l-1 I-. The carotenoid:chlorophyll a ratio of the
      parent strains increased after cobalt addition. The cobalt-adapted strain showed
      a much higher ratio than the cobalt-grown parent (sensitive) cells which remained
      unchanged after cobalt addition. Intracellular CO2+ uptake by the cells was
      concentration-dependent and followed Michaelis-Menten kinetics with saturation in
      uptake occurring in the parent and adapted strains at 126 and 189 mumol l-1 Co2+,
      respectively. At saturating concentrations, the maximum CO2+ uptake was 39.73 and
      158.43 nmol CO2+ mg-1 protein, respectively for the parent and adapted strains.
      The adapted strain also showed greater cobalt adsorption. The Km of intracellular
      CO2+ uptake was lower in the case of adapted cells as compared with the parent,
      whereas Vmax showed an opposite trend. Thus, the adapted cells appear to be more
      efficient than the parent strain in intracellular uptake of cobalt. Differences
      between kinetic constants of both the strains suggest that the strains may be
      physiologically different. Likewise, iodide uptake was significantly higher in
      iodide-adapted cells than in controls.

PMID- 8144417
TI  - Isolation of Legionella from water samples using various culture methods.
AB  - The efficacy of a non-selective medium and two selective media were compared for
      the isolation of legionellas from water samples. The effect of acid wash
      treatment for decontamination of the water samples on the isolation frequency of
      legionellas was also studied. The 236 samples were taken from cooling,
      humidifying and drinking water systems; 21% were legionella-positive when
      inoculated directly on modified Wadowsky-Yee (MWY) medium and 26% were positive
      when concentrated (x 200) before cultivation on MWY or CCVC media. Inoculation on
      MWY medium after concentration followed by decontamination by the acid-wash
      technique gave the highest isolation frequency (31%). The lowest frequency (8%)
      was found with the non-selective BCYE alpha medium. An isolation frequency of 28%
      was achieved with the BCYE alpha medium after concentration and acid-wash
      treatment of the samples. Forty per cent of the samples were positive for
      legionellas when the results from all the culture methods were combined. Not all
      the legionella-positive samples were identified by a single culture method.
      Ninety-three of the 95 positive samples were detected with the two best
      combinations of three culture methods. The best culture method for detecting
      legionellas depended on the source of the water sample. Some water quality
      characteristics, like temperature and organic matter content, affected the
      isolation frequency of Legionella spp.

PMID- 8144418
TI  - Storage of poultry meat under modified atmospheres or vacuum packs: possible role
      of microbial metabolites as indicator of spoilage.
AB  - The effect of carbon dioxide (100%), nitrogen (100%), carbon dioxide/oxygen
      (20%:80%) or vacuum pack at 3 and 10 degrees C was studied on the microbial
      flora, in skinless poultry breast fillets or thigh meat. Lactic acid bacteria and
      Brochothrix thermosphacta were the predominant organisms in samples stored in
      vacuum packs, carbon dioxide and nitrogen. Pseudomonads grew only in
      oxygen/carbon dioxide packaging systems. The concentration of lactate diminished
      in both thigh and breast meat during storage at 3 and 10 degrees C. This decrease
      was more pronounced in thigh meat stored under 20%:80% carbon dioxide/oxygen.
      Acetate increased to varying degrees in all samples regardless of the storage
      conditions.

PMID- 8144419
TI  - Dosage recommendations for teicoplanin.

PMID- 8144420
TI  - In-vitro activities of quinolones against mycobacteria.
AB  - From the results of recently-published in-vitro studies, we have reviewed the
      activities of novel quinolones which are currently available, either commercially
      or for investigative purposes, against Mycobacterium tuberculosis, the atypical
      mycobacteria (principally the Mycobacterium avium complex, Mycobacterium
      chelonae, Mycobacterium xenopi, Mycobacterium marinum and Mycobacterium
      fortuitum) and Mycobacterium leprae. We have also evaluated the effects of the
      various methods for determining the susceptibilities of the mycobacteria on the
      in-vitro activities of these agents. Sparfloxacin, Win-57273, ciprofloxacin and
      ofloxacin were the most active agents overall. The in-vitro activities,
      efficacies in animal models, tissue and cell penetration and results of
      preliminary clinical investigations suggest that some of the newer quinolones
      might be effective alternatives to standard anti-tuberculous agents for the
      treatment of patients with infections caused by mycobacteria, particularly when
      there is resistance to the latter group of drugs.

PMID- 8144421
TI  - Evaluation of five different methods to prepare bacterial extracts for the
      identification of beta-lactamases by isoelectric focusing.
AB  - The X-PRESS, osmotic shock, chloroform treatment, lysozyme treatment and
      ultrasonic disruption methods to release five different plasmid-mediated beta
      lactamases from Escherichia coli and one chromosomal beta-lactamase from
      Enterobacter cloacae were compared. The main activities of TEM-1, SHV-1, OXA-1,
      OXA-2, PSE-4 and chromosomal P99 beta-lactamases were found at the same
      isoelectric point irrespective of the method used. However, additional satellite
      bands were found with TEM-1, OXA-1, OXA-2 and PSE-4 beta-lactamases released by
      the lysozyme method. In addition, beta-lactamase released by osmotic shock
      treatment was found to be unstable during storage at -20 degrees C or during the
      18 h period of iso-electric focusing at +4 degrees C. Chloroform treatment
      produced similar band patterns and at least as good an enzyme yield as ultrasonic
      disintegration and was equally simple and fast to perform.

PMID- 8144422
TI  - In-vitro activity of the new triazole D0870 compared with amphotericin B and
      itraconazole against Aspergillus spp.
AB  - The in-vitro activity of D0870, a new triazole, was compared with amphotericin B
      (AMP B) and itraconazole (ITZ) against 40 Aspergillus isolates, which included 25
      isolates of Aspergillus fumigatus, using a broth macro-dilution method at 37
      degrees C. Minimum inhibitory concentration (MIC) and minimum fungicidal
      concentration (MFC) (killing of > or = 98%) were measured. For 40 isolates,
      geometric mean (GM) MIC values and ranges were D0870 10.55 and 2-32, ITZ 2.26 and
      0.5-64, AMP B 2.42 and 1-64 mg/L. Differences in susceptibilities between species
      were apparent with Aspergillus flavus (n = 5) being the most susceptible to D0870
      (GM 2.64, range 2-8 mg/L). MFC values were within one dilution of the MIC value
      for 90% of isolates (D0870 and ITZ) and 95% of isolates (AMP B). In
      reproducibility studies, seven, eight and four of eight isolates retested gave
      MIC results within one dilution for D0870, AMP B, and ITZ, respectively.
      Therefore, in-vitro mould testing with D0870 is feasible and reproducible with
      clear MIC and MFC end-points. D0870 is active against most Aspergillus spp., but
      at higher concentrations than either ITZ or AMP B.

PMID- 8144423
TI  - The in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis.
AB  - The in-vitro activity of a group of antifungal compounds known to inhibit
      ergosterol synthesis was investigated against Leishmania donovani grown as
      intracellular amastigotes in the human leukaemia monocyte cell line, THP-1.
      Toxicity on the host cells was assessed using the colorimetric MTT assay.
      Compounds inhibiting 2,3 oxidosqualene lanosterol cyclase; RO 43-3815, RO 43
      5955, RO 43-8208, RO 42-6589 and RO 43-0688 displayed high activity with a median
      effective dose (ED50) of 0.6, 0.9, 3.5, 2.2 and 0.7 mg/L respectively. Of the
      azole compounds, oxiconazole had an ED50 value of 3.3 mg/L while ketoconazole
      showed the least activity. The delta-14-reductase and delta-8-delta-7 isomerase
      inhibitor, amorolfine, gave the highest therapeutic index with an ED50 value of
      1.6 mg/L. Most compounds tested had a lower ED50 value than the standard
      antileishmanial drugs, sodium stibogluconate (5.5 mg Sbv/L) and meglumine
      antimoniate (3.0 mg Sbv/L) indicating the clean potential of these antifungal
      compounds in treating leishmaniasis.

PMID- 8144424
TI  - Influence of the pre-treatment duration of infection on the efficacies of various
      antibiotic regimens in experimental streptococcal endocarditis.
AB  - The influence of the pre-treatment duration of infection on the efficacies of
      three different antibiotic regimens was investigated in a rabbit model of
      subacute endocarditis caused by a novel, nutritionally-variant species,
      Streptococcus adjacens strain GaDT. Treatment was initiated either 6 or 10 days
      after bacterial inoculation (days 7 and 11 respectively) and comprised procaine
      penicillin (150,000 IU/kg bd), alone or combined with tobramycin (12 mg/kg od),
      teicoplanin (10 mg/kg bd), all administered by the intramuscular route for 4
      days. The MICs and MBCs of penicillin, tobramycin and teicoplanin were 0.015 and
      1 mg/L, 8 and 16 mg/L and 0.25 and 256 mg/L respectively. In the control rabbits,
      the mean (+/- S.D.) weights of the vegetations were 25 +/- 16 mg on day 7 and 45
      +/- 34 mg on day 11 (P = 0.06). The mean (+/- S.D.) reductions in the number of
      cfu in the vegetations of the treated groups of animals after completion of
      therapy which had been started on days 7 and 11, compared with the mean numbers
      of cfu in the vegetations of the untreated controls on days 7 and 11 (delta log10
      cfu/g), were 4.0 +/- 1.3 and 2.1 +/- 1.5 respectively for penicillin (P < 0.05),
      3.2 +/- 1.8 and 2.4 +/- 1.8 respectively for teicoplanin and 5.4 +/- 1.2 and 5.2
      +/- 1.2 respectively for the combination of penicillin and tobramycin. The
      increase in the size of the vegetations and changes in the metabolism of the
      bacteria within the vegetations between days 7 and 11, as demonstrated by
      electron microscopy, might explain why penicillin was more effective earlier in
      the course of the disease and why the influence of the duration of infection
      before treatment was initiated, varied according to the antibiotic regimen. These
      results suggest that the use of bactericidal regimens, such as the combination of
      penicillin and tobramycin, which are equally effective in reducing the bacterial
      counts in vegetations which have been infected for both long and short periods
      could minimize the risk of relapse in patients with endocarditis in whom there
      have been long delays before initiating treatment and/or who have large
      vegetations.

PMID- 8144425
TI  - The pharmacokinetics, tissue penetration and in-vitro activity of loracarbef, a
      beta-lactam antibiotic of the carbacephem class.
AB  - The pharmacokinetics of loracarbef in plasma and a mild inflammatory exudate were
      studied in human volunteers. After a single oral dose of 400 mg, a mean maximum
      drug concentration (Cmax) of 17.8 mg/L was achieved in the plasma at 1.2 h (mean
      Tmax). The mean plasma elimination half-life (T1/2) was 1.3 h. In the
      inflammatory exudate the mean Cmax was 8.9 mg/L at a mean Tmax of 2.0 h and with
      a mean T1/2 of 1.7 h. The mean penetration into the inflammatory exudate was
      90.1%. The in-vitro activity of loracarbef was determined against Haemophilus
      influenzae and Moraxella catarrhalis (MIC90s of 4 mg/L and 1 mg/L respectively,
      regardless of beta-lactamase production), as well as Streptococcus pneumoniae
      (MIC90 of 2 mg/L). Loracarbef was also active against Escherichia coli, Proteus
      mirabilis and Klebsiella pneumoniae (MIC90s of < or = 2 mg/L). The in-vitro
      activity and pharmacokinetics of loracarbef suggest that it would be efficative
      therapy for patients with community-acquired respiratory and urinary tract
      infections caused by the most frequently-encountered bacterial pathogens.

PMID- 8144426
TI  - The penetration of rufloxacin into sites of potential infection in the
      respiratory tract.
AB  - The concentrations of rufloxacin in the bronchial mucosal, pulmonary epithelial
      lining fluid and alveolar macrophages were determined in specimens obtained at
      fibreoptic bronchoscopy. A single oral dose of rufloxacin 400 mg was administered
      and the samples obtained in the following 72 h. The mean peak serum concentration
      was 3.56 mg/L, yet the agent was concentrated 1.8-fold in bronchial mucosa, 21.6
      fold in alveolar macrophages and 7.7-fold in epithelial lining fluid (as measured
      by AUC ratios).

PMID- 8144427
TI  - The early bactericidal activity of rifabutin in patients with pulmonary
      tuberculosis measured by sputum viable counts: a new method of drug assessment.
AB  - The activity of rifabutin and rifampicin against rapidly growing, extra-cellular
      Mycobacterium tuberculosis in cavity walls was measured by counting colony
      forming units (cfu) in the sputum of 74 patients with newly diagnosed, severe
      pulmonary tuberculosis during the first 2 days of daily chemotherapy. The fall in
      counts, (log10 cfu/mL sputum/day), was termed the early bactericidal activity
      (EBA). The EBA, a highly reproducible measure within groups of 10-13 patients,
      was -0.015 for a low EBA reference group (who received no chemotherapy) and 0.495
      for a high EBA reference group (who received 300 mg isoniazid daily). The EBAs in
      patients receiving 300 and 600 mg rifabutin were 0.014 and 0.075, and for those
      taking 150, 300 and 600 mg rifampicin 0.021, 0.150 and 0.204, respectively.
      Weight-for-weight, the ratio rifabutin to rifampicin producing the same EBA was
      estimated to be 2.73 (95% confidence limits 1.96-3.78). Determination of the EBA
      is a rapid and economical method of comparing the potency in human lesions of
      drugs of the same type before embarking on a conventional clinical trial.

PMID- 8144429
TI  - Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in
      Finland.

PMID- 8144428
TI  - In-vitro comparison of DU-6859a, a novel fluoroquinolone, with other quinolones
      and oral cephalosporins tested against 5086 recent clinical isolates.

PMID- 8144430
TI  - Netilmicin cerebrospinal fluid concentrations after an intravenous infusion of
      400 mg in patients without meningeal inflammation.

PMID- 8144431
TI  - Safety profile of ciprofloxacin during long-term therapy for pulmonary
      tuberculosis.

PMID- 8144432
TI  - Antimicrobial activities of N-acetylcysteine and some non-steroidal
      antiinflammatory drugs.

PMID- 8144433
TI  - Endotoxin release and TNF production: a reappraisal.

PMID- 8144434
TI  - Intravascular catheters impregnated with benzalkonium chloride.

PMID- 8144435
TI  - Campylobacter spp antibiotic susceptibility.

PMID- 8144436
TI  - In-vitro susceptibility of Alcaligenes faecalis compared with those of other
      Alcaligenes spp. to antimicrobial agents including seven beta-lactams.

PMID- 8144437
TI  - Early susceptibility test results with the Bacteroides fragilis group.

PMID- 8144438
TI  - In-vitro antimicrobial studies with the combination of cefoperazone and
      sulbactam.

PMID- 8144439
TI  - Synergy testing of macrolide combinations using the chequerboard technique.

PMID- 8144440
TI  - Postantibiotic effects of E-4868 and OPC-17116.

PMID- 8144441
TI  - In-vivo and in-vitro study of the postantibiotic effect of meropenem.

PMID- 8144442
TI  - Activity of beta-lactam antibiotics in an animal model against methicillin
      resistant Staphylococcus aureus.

PMID- 8144443
TI  - Correlation of vancomycin clearance and creatinine clearance: unreliability for
      predicting initial dosing in neutropenic haematological patients.

PMID- 8144444
TI  - Meropenem treatment of post-traumatic meningitis due to Pseudomonas aeruginosa.

PMID- 8144445
TI  - D-loops and R-loops: alternative mechanisms for the initiation of chromosome
      replication in Escherichia coli.

PMID- 8144446
TI  - Interactions between a Bacillus subtilis anti-sigma factor (RsbW) and its
      antagonist (RsbV).
AB  - The activity of sigma B, a secondary sigma factor of Bacillus subtilis, is
      primarily controlled by an anti-sigma factor protein (RsbW) that binds to sigma B
      and blocks its ability to form an RNA polymerase holoenzyme (E-sigma B).
      Inhibition of sigma B by RsbW is counteracted by RsbV, a protein that is
      essential for the activation of sigma B-dependent transcription. When crude B.
      subtilis extracts were fractionated by gel filtration chromatography or
      electrophoresis through nondenaturing polyacrylamide gels, a complex composed of
      RsbW and RsbV that is distinct from the previously observed RsbW-sigma B complex
      was detected. In analogous experiments, RsbX, an additional regulator of sigma B
      dependent transcription that is thought to act independently of RsbV-RsbW, was
      not found to associate with any of the other sigB operon products. Two forms of
      RsbV were visualized when crude cell extracts of B. subtilis were subjected to
      isoelectric focusing (IEF), with the more negatively charged RsbV species absent
      from extracts prepared from RsbW- strains. In vitro, RsbV became phosphorylated
      when incubated with ATP and RsbW but not with ATP alone. The phosphorylated RsbV
      species comigrated during IEF with the RsbW-dependent form of RsbV found in crude
      cell extracts. These results suggest that the modified RsbV, present in crude
      cell extracts, is phosphorylated. When gel filtration fractions containing RsbV
      RsbW complexes or RsbV alone were subjected to IEF, only the unmodified form of
      RsbV was found associated with RsbW. The presumed phosphorylated variant of RsbV
      was present only in fractions that did not contain RsbW. The data support a model
      whereby RsbV binds directly to RsbW and blocks its ability to form the RsbW-sigma
      B complex. This activity of RsbV appears to be inhibited by RsbW-dependent
      phosphorylation.

PMID- 8144447
TI  - Pseudomonas aeruginosa AlgG is a polymer level alginate C5-mannuronan epimerase.
AB  - Alginate is a viscous extracellular polymer produced by mucoid strains of
      Pseudomonas aeruginosa that cause chronic pulmonary infections in patients with
      cystic fibrosis. Alginate is polymerized from GDP-mannuronate to a linear polymer
      of beta-1-4-linked residues of D-mannuronate and its C5-epimer, L-guluronate. We
      previously identified a gene called algG in the alginate biosynthetic operon that
      is required for incorporation of L-guluronate residues into alginate. In this
      study, we tested the hypothesis that the product of algG is a C5-epimerase that
      directly converts D-mannuronate to L-guluronate. The DNA sequence of algG was
      determined, and an open reading frame encoding a protein (AlgG) of approximately
      60 kDa was identified. The inferred amino terminus of AlgG protein contained a
      putative signal sequence of 35 amino acids. Expression of algG in Escherichia
      coli demonstrated both 60-kDa pre-AlgG and 55-kDa mature AlgG proteins, the
      latter of which was localized to the periplasm. An N-terminal analysis of AlgG
      showed that the signal sequence was removed in the mature form. Pulse-chase
      experiments in both E. coli and P. aeruginosa provided evidence for conversion of
      the 60- to the 55-kDa size in vivo. Expression of algG from a plasmid inan algG
      (i.e., polymannuronate-producing) mutant of P. aeruginosa restored production of
      an alginate containing L-guluronate residues. The observation that AlgG is
      apparently processed and exported from the cytoplasm suggested that it may act as
      a polymer-level mannuronan C5-epimerase. An in vitro assay for mannuronan C5
      epimerization was developed wherein extracts of E. coli expressing high levels of
      AlgG were incubated with polymannuronate. Epimerization of D-mannuronate to L
      guluronate residues in the polymer was detected enzymatically, using a L
      guluronate-specific alginate lyase of Klebsiella aerogenes. Epimerization was
      also detected in the in vitro reaction between recombinant AlgG and poly-D
      mannuronate, using high-performance anion-exchange chromatography. The
      epimerization reaction was detected only when acetyl groups were removed from the
      poly-D-mannuronate substrate, suggesting that AlgG epimerization activity in vivo
      may be sensitive to acetylation of the D-mannuronan residues. These results
      demonstrate that AlgG has polymer-level mannuronan C5-epimerase activity.

PMID- 8144448
TI  - Regulation of the Escherichia coli lrp gene.
AB  - Lrp (leucine-responsive regulatory protein) is a major Escherichia coli
      regulatory protein which regulates expression of a number of operons, some
      negatively and some positively. This work relates to a characterization of lrp,
      the gene encoding Lrp. Nucleotide sequencing established that the coding regions
      of lrp and trxB (encoding thioredoxin reductase) are separated by 543 bp and that
      the two genes are transcribed in opposite directions. In addition, we used primer
      extension, deletion analyses, and lrp-lacZ transcriptional fusions to delineate
      the promoter and regulatory region of the lrp operon. The lrp promoter is located
      267 nucleotides upstream of the translational start codon of the lrp gene. In
      comparison with a wild-type strain, expression of the lrp operon was increased
      about 3-fold in a strain lacking Lrp and decreased about 10-fold in a strain
      overproducing Lrp. As observed from DNA mobility shift and DNase I footprinting
      analyses, Lrp binds to one or more sites within the region -80 to -32 relative to
      the start point of lrp transcription. A mutational analysis indicated that this
      same region is at least partly required for repression of lrp expression in vivo.
      These results demonstrate that autogenous regulation of lrp involves Lrp acting
      directly to cause repression of lrp transcription.

PMID- 8144449
TI  - Cloning, sequencing, and overexpression in Escherichia coli of the alpha-D
      glucose-1-phosphate cytidylyltransferase gene isolated from Yersinia
      pseudotuberculosis.
AB  - A clone of Yersinia pseudotuberculosis DNA carrying the ascA gene was
      constructed, and the corresponding protein was successfully overexpressed in
      Escherichia coli. A protocol consisting of DEAE-cellulose and Sephadex G-100
      column chromatography was developed and led to a nearly homogeneous purification
      of the ascA product. Initial characterization showed that the ascA-encoded
      protein is actually the alpha-D-glucose-1-phosphate cytidylyltransferase which
      catalyzes the first step of the biosynthesis of CDP-ascarylose (CDP-3,6-dideoxy-L
      arabino-hexose), converting alpha-D-glucose-1-phosphate to CDP-D-glucose. In
      contrast to early studies suggesting that this enzyme was a monomeric protein of
      111 kDa, the purified cytidylyltransferase from Y. pseudotuberculosis was found
      to consist of four identical subunits, each with a molecular mass of 29 kDa. This
      assignment is supported by the fact that the ascA gene, as a part of the
      ascarylose biosynthetic cluster, exhibits high sequence homology with other
      nucleotidylyltransferases, and its product shows high cytidylyltransferase
      activity. Subsequent amino acid comparison with other known
      nucleotidylyltransferases has allowed a definition of the important active-site
      residues within this essential catalyst. These comparisons have also afforded the
      inclusion of the cytidylyltransferase into the mechanistic convergence displayed
      by this fundamental class of enzyme.

PMID- 8144450
TI  - Analysis of the binding site of the LysR-type transcriptional activator TcbR on
      the tcbR and tcbC divergent promoter sequences.
AB  - The TcbR transcriptional activator protein, which is encoded by the tcbR gene of
      Pseudomonas sp. strain P51 (J. R. van der Meer, A. C. J. Frijters, J. H. J.
      Leveau, R. I. L. Eggen, A. J. B. Zehnder, and W. M. de Vos, J. Bacteriol.
      173:3700-3708, 1991), was purified from overproducing Escherichia coli cells by
      using a two-step chromatographic procedure. Subsequent use of TcbR in gel
      mobility shift assays with progressively shortened portions of a DNA fragment
      containing the divergent promoter sequences of the tcbR gene and the tcbCDEF
      operon showed that the direct binding site of TcbR is located between positions 
      85 to -40 relative to the tcbCDEF transcriptional start site, containing a LysR
      type recognition sequence motif (T-N11-A). DNase I footprinting experiments
      revealed that TcbR protected an area on both strands of the intercistronic region
      which was actually larger than this binding site (from positions -74 to -24).
      This stretch of protected DNA was interrupted by a region (positions -52 to -37)
      which became strongly hypersensitive to DNase I digestion upon addition of TcbR,
      suggesting that TcbR induces a bend in the DNA at this site.

PMID- 8144451
TI  - Role of signal peptides in targeting of proteins in cyanobacteria.
AB  - Proteins of cyanobacteria may be transported across one of two membrane systems:
      the typical eubacterial cell envelope (consisting of an inner membrane,
      periplasmic space, and an outer membrane) and the photosynthetic thylakoids. To
      investigate the role of signal peptides in targeting in cyanobacteria,
      Synechococcus sp. strain PCC 7942 was transformed with vectors carrying the
      chloramphenicol acetyltransferase reporter gene fused to coding sequences for one
      of four different signal peptides. These included signal peptides of two proteins
      of periplasmic space origin (one from Escherichia coli and the other from
      Synechococcus sp. strain PCC 7942) and two other signal peptides of proteins
      located in the thylakoid lumen (one from a cyanobacterium and the other from a
      higher plant). The location of the gene fusion products expressed in
      Synechococcus sp. strain PCC 7942 was determined by a chloramphenicol
      acetyltransferase enzyme-linked immunosorbent assay of subcellular fractions. The
      distribution pattern for gene fusions with periplasmic signal peptides was
      different from that of gene fusions with thylakoid lumen signal peptides. Primary
      sequence analysis revealed conserved features in the thylakoid lumen signal
      peptides that were absent from the periplasmic signal peptides. These results
      suggest the importance of the signal peptide in protein targeting in
      cyanobacteria and point to the presence of signal peptide features conserved
      between chloroplasts and cyanobacteria for targeting of proteins to the thylakoid
      lumen.

PMID- 8144452
TI  - Cloning, characterization, and nucleotide sequence analysis of the argH gene from
      Campylobacter jejuni TGH9011 encoding argininosuccinate lyase.
AB  - The complete structural gene for argininosuccinate lyase (argH) from
      Campylobacter jejuni TGH9011 has been cloned into Escherichia coli by
      complementation of an E. coli argH auxotrophic mutant. The gene has been
      subcloned for sequencing on a 4.1-kb DNA segment and localized by the
      complementing activity of deletion mutants. The complete DNA sequence of the C.
      jejuni argH gene was determined. The transcription start point for argH mRNA was
      determined by primer extension analysis and found to be within the coding
      sequence of the upstream gene, identified as the phosphoenolpyruvate
      carboxykinase gene (ppc). The argininosuccinate lyase and the phosphoenolpyruvate
      carboxykinase reading frames overlap by one base, the second example of this
      phenomenon in C. jejuni chromosomal genes. The enzyme has a deduced subunit
      molecular weight of 51,831. Recombinant plasmids containing the argH gene
      generate a 56-kDa protein and a 43-kDa protein in E. coli maxicells. An alternate
      translation initiation producing a polypeptide with a deduced molecular mass of
      42 kDa may account for the smaller protein observed in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The C. jejuni argH gene shows nucleotide
      homology to both yeast and human argininosuccinate lyase genes, and conserved
      amino acid domains are evident between the corresponding proteins.

PMID- 8144453
TI  - Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: analysis of
      the genes in the FUN38-MAK16-SPO7 region.
AB  - Transcribed regions on a 42-kb segment of chromosome I from Saccharomyces
      cerevisiae were mapped. Polyadenylated transcripts corresponding to eight
      previously characterized genes (MAK16, LTE1, CCR4, FUN30, FUN31, TPD3, DEP1, and
      CYS3) and eight new genes were identified. All transcripts were present at one to
      four copies per cell except for one which was significantly less abundant. This
      region has been sequenced, and the sizes, locations, and orientations of the
      transcripts were in nearly perfect agreement with the open reading frames.
      Disruptions in eight genes identified solely on the basis of a transcribed
      region, FUN38, FUN25, FUN26, FUN28, FUN30, FUN31, FUN33, and FUN34, indicated
      that all were nonessential for growth on rich medium at 30 degrees C. Disruption
      of FUN30, a gene closely related to RAD16 and RAD54, surprisingly resulted in
      increased resistance to UV irradiation. No additional phenotypes, other than slow
      growth, were observed for all other mutants. The distribution of essential genes
      on chromosome I is discussed.

PMID- 8144454
TI  - Circadian rhythms of cyanobacteria: monitoring the biological clocks of
      individual colonies by bioluminescence.
AB  - Reproducible circadian rhythms of bioluminescence from individual colonies of
      cyanobacteria (Synechococcus sp. strain PCC 7942) has been observed. Phenotypic
      monitoring of colonies on agar plates will enable us to genetically analyze the
      molecular mechanism of the circadian clock of cyanobacteria by screening for
      clock mutants. By the introduction of a bacterial luciferase gene, we previously
      developed a transformed cyanobacterial strain (AMC149) that expresses luciferase
      as a bioluminescent reporter of the circadian clock. In liquid culture, AMC149
      expresses a rhythm of bioluminescence that displays the same behavior as
      circadian rhythms in higher eukaryotes. Improvements in the technique for
      administering the reporter enzyme's substrate (decanal) and a highly sensitive
      photon-counting camera allow monitoring the bioluminescence of single colonies.
      Individual colonies on agar plates displayed a rhythmicity which is essentially
      the same as that previously reported for liquid cultures.

PMID- 8144455
TI  - Catabolite repression of the Bacillus subtilis hut operon requires a cis-acting
      site located downstream of the transcription initiation site.
AB  - Expression of the Bacillus subtilis hut operon is subject to regulation by
      catabolite repression. A set of hut-lacZ transcriptional fusions was constructed
      and used to identify two cis-acting sites involved in catabolite repression. The
      hutOCR1 operator site lies immediately downstream of the hut promoter and weakly
      regulates hut expression in response to catabolite repression. The downstream
      hutOCR2 operator site lies within the hutP gene, between positions +203 and +216,
      and is required for wild-type levels of catabolite repression. Both the hutOCR1
      and hutOCR2 operators have sequence similarity to the sites which mediate
      catabolite repression of several other B. subtilis genes. Two mutations which
      relieve catabolite repression of hut expression were found to alter the
      nucleotide sequence of the hutOCR2 operator. Catabolite repression of hut
      expression was partially relieved in strains containing the ccpA mutation but not
      in strains containing either the pai or hpr mutation.

PMID- 8144456
TI  - Modulation of Bacillus subtilis catabolite repression by transition state
      regulatory protein AbrB.
AB  - The first enzyme of the Bacillus subtilis histidine-degradative (hut) pathway,
      histidase, was expressed at higher levels during the onset of the stationary
      growth phase in nutrient sporulation medium in early-blocked sporulation mutants
      (spo0A) than in wild-type strains. Histidase expression was also elevated in
      spo0A mutant cultures compared with wild-type cultures during the logarithmic
      growth phase in minimal medium containing slowly metabolized carbon sources.
      Histidase expression was not derepressed in spo0A abrB mutant cultures under
      these growth conditions, suggesting that the AbrB protein is responsible for the
      derepression of histidase synthesis seen in spo0A mutant cultures. spo0A mutants
      contain higher levels of the AbrB protein than do wild-type strains because the
      Spo0A protein represses AbrB expression. A direct correlation between the levels
      of abrB transcription and histidase expression was found in spo0A mutant
      cultures. The hutOCR2 operator, which is required for wild-type regulation of hut
      expression by catabolite repression, was also required for AbrB-dependent
      derepression of hut expression in spo0A mutants. Purified AbrB protein bound to
      the hutOCR2 operator in vitro, suggesting that AbrB protein alters hut expression
      by competing with the hut catabolite repressor protein for binding to the hutOCR2
      site. During the logarithmic growth phase in media containing slowly metabolized
      carbon sources, the expression of several other enzymes subject to catabolite
      repression was elevated in spo0A mutants but not in spo0A abrB mutants. This
      suggests that the AbrB protein acts as a global modulator of catabolite
      repression during carbon-limited growth.

PMID- 8144457
TI  - Root colonization and systemic spreading of Azoarcus sp. strain BH72 in grasses.
AB  - The invasive properties of Azoarcus sp. strain BH72, an endorhizospheric isolate
      of Kallar grass, on gnotobiotically grown seedlings of Oryza sativa IR36 and
      Leptochloa fusca (L.) Kunth were studied. Additionally, Azoarcus spp. were
      localized in roots of field-grown Kallar grass. To facilitate localization and to
      assure identity of bacteria, genetically engineered microorganisms expressing
      beta-glucuronidase were also used as inocula. beta-Glucuronidase staining
      indicated that the apical region of the root behind the meristem was the most
      intensively colonized. Light and electron microscopy showed that strain BH72
      penetrated the rhizoplane preferentially in the zones of elongation and
      differentiation and colonized the root interior inter- and intracellularly. In
      addition to the root cortex, stelar tissue was also colonized; bacteria were
      found in the xylem. No evidence was obtained that Azoarcus spp. could reside in
      living plant cells; rather, plant cells were apparently destroyed after bacteria
      had penetrated the cell wall. A common pathogenicity test on tobacco leaves
      provided no evidence that representative strains of Azoarcus spp. are
      phytopathogenic. Compared with the control, inoculation with strain BH72
      significantly promoted growth of rice seedlings. This effect was reversed when
      the plant medium was supplemented with malate (0.2 g/liter). N2 fixation was
      apparently not involved, because the same response was obtained with a nifK
      mutant of strain BH72, which has a Nif- phenotype. Also, Western blot
      (immunoblot) analysis of protein extracts from rice seedlings gave no indication
      that nitrogenase was present. PCR and Western immunoblotting, using primers
      specific for eubacteria and antibodies recognizing type-specific antigens,
      respectively, indicated that strain BH72 could colonize rice plants systemically,
      probably mediated by longitudinal spreading through vessels.

PMID- 8144458
TI  - The nature of the traK4 mutation in the F sex factor of Escherichia coli.
AB  - The sequence of traK gene of the F sex factor of Escherichia coli is presented;
      the traK gene product is predicted to be a protein of 25,627 Da with a signal
      sequence of 21 amino acids to give a mature protein of 23,307 Da. The traK4
      mutation is an extremely polar mutation in the F plasmid that affects F pilus
      synthesis and plasmid transfer. traK genes carrying the traK4 mutation and a
      nonpolar mutation traK105 were cloned, sequenced, and identified as an amber
      nonsense and a frameshift mutation, respectively. The traK4 mutation occurred
      within one predicted rho-dependent transcription termination element (TTE) and
      immediately upstream of another, while the traK105 mutation occurred after the
      two potential TTEs within the traK gene. S1 nuclease protection analysis and
      Northern (RNA) blot analysis were used to confirm that the traK4 mutation, but
      not the traK105 mutation, caused premature termination of transcription. Computer
      analysis of the F transfer region suggested the presence of TTE motifs at regular
      intervals throughout the 33.4-kb sequence.

PMID- 8144459
TI  - Independent phylogenetic origins of methanotrophic and chemoautotrophic bacterial
      endosymbioses in marine bivalves.
AB  - The discovery of bacterium-bivalve symbioses capable of utilizing methane as a
      carbon and energy source indicates that the endosymbionts of hydrothermal vent
      and cold seep bivalves are not restricted to sulfur-oxidizing chemoautotrophic
      bacteria but also include methanotrophic bacteria. The phylogenetic origin of
      methanotrophic endosymbionts and their relationship to known symbiotic and free
      living bacteria, however, have remained unexplored. In situ localization and
      phylogenetic analysis of a symbiont 16S rRNA gene cloned from the gills of a
      recently described deep-sea mussel species demonstrate that this symbiont
      represents a new taxon which is closely related to free-living, cultivable Type I
      methanotrophic bacteria. This symbiont is distinct from known chemoautotrophic
      symbionts. Thus, despite compelling similarities between the symbioses,
      chemoautotrophic and methanotrophic symbionts of marine bivalves have independent
      phylogenetic origins.

PMID- 8144460
TI  - Rapid viability loss on exposure to air in a superoxide dismutase-deficient
      mutant of Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis, an obligate anaerobe, exhibits a relatively high degree
      of aerotolerance and possesses superoxide dismutase (SOD) which is induced by
      exposure to air. To clarify roles for SOD in this organism, the gene encoding SOD
      (sod) on the P. gingivalis chromosome was disrupted in a gene-directed way by use
      of a suicide plasmid containing a mutated sod. A sod mutant thus obtained showed
      no SOD activity in crude extracts and exhibited a rapid viability loss
      immediately after exposure to air, whereas the wild-type parent showed no
      decrease in viability for at least 5 h under aerobic conditions. These results
      clearly indicate that SOD is essential for aerotolerance in P. gingivalis.

PMID- 8144461
TI  - Expression of the Prevotella loescheii adhesin gene (plaA) is mediated by a
      programmed frameshifting hop.
AB  - The 2.4-kb plaA gene, which encodes a Prevotella loescheii galactoside-specific
      adhesin, contains a programmed frameshifting hop. The frameshift region consists
      of two UAA termination codons, two repeats of four identical bases between the
      terminators, and a stem-loop structure that has the potential to form a
      pseudoknot located downstream from the second UAA. The stem-loop and pseudoknot
      are features found in a number of retroviruses where frameshifting is a more
      common occurrence. The terminators, sequence repeats, and secondary structures
      were identified in both the P. loescheii plaA gene and the mRNA transcript. An in
      frame fusion of the entire plaA frameshift region between codons 9 and 10 of the
      lacZ gene permitted relatively efficient expression (4 to 25% of that of the
      control) of beta-galactosidase in Escherichia coli.

PMID- 8144462
TI  - The lipA gene of Serratia marcescens which encodes an extracellular lipase having
      no N-terminal signal peptide.
AB  - The lipA gene encoding an extracellular lipase was cloned from the wild-type
      strain of Serratia marcescens Sr41. Nucleotide sequencing showed a major open
      reading frame encoding a 64.9-kDa protein of 613 amino acid residues; the deduced
      amino acid sequence contains a lipase consensus sequence, GXSXG. The lipase had
      66 and 56% homologies with the lipases of Pseudomonas fluorescens B52 and P.
      fluorescens SIK W1, respectively, but did not show any overall homology with
      lipases from other origins. The Escherichia coli cells carrying the S. marcescens
      lipA gene did not secrete the lipase into the medium. The S. marcescens lipase
      had no conventional N-terminal signal sequence but was also not subjected to any
      processing at both the N-terminal and C-terminal regions. A specific short region
      similar to the regions of secretory proteins having no N-terminal signal peptide
      was observed in the amino acid sequence. Expression of the lipA gene in S.
      marcescens was affected by the carbon source and the addition of Tween 80.

PMID- 8144463
TI  - Genetics of the serine cycle in Methylobacterium extorquens AM1: identification
      of sgaA and mtdA and sequences of sgaA, hprA, and mtdA.
AB  - In a previous paper, we reported identification of the 5' part of hprA of
      Methylobacterium extorquens AM1, which encodes the serine cycle enzyme
      hydroxypyruvate reductase (L. V. Chistoserdova and M. E. Lidstrom, J. Bacteriol.
      174:71-77, 1992). Here we present the complete sequence of hprA and partial
      sequence of genes adjacent to hprA. Upstream of hprA, the 3' part of an open
      reading frame was discovered, separated from hprA by 263 bp. This open reading
      frame was identified as the gene encoding another serine cycle enzyme, serine
      glyoxylate aminotransferase (sgaA). Cells containing an insertion mutation into
      sgaA were unable to grow on C1 compounds, demonstrating that the gene is required
      for C1 metabolism. Sequencing downstream of hprA has revealed the presence of
      another open reading frame (mtdA), which is probably cotranscribed with hprA.
      This open reading frame was identified as the gene required for the synthesis of
      5,10-methylenetetrahydrofolate dehydrogenase. Our data suggest that this enzyme
      plays an integral role in methylotrophic metabolism in M. extorquens AM1, either
      in formaldehyde oxidation or as part of the serine cycle.

PMID- 8144464
TI  - FixL of Rhizobium meliloti enhances the transcriptional activity of a mutant
      FixJD54N protein by phosphorylation of an alternate residue.
AB  - In Rhizobium meliloti, transcription of nitrogen fixation genes is induced in
      oxygen-depleted conditions under the control of the two-component regulatory
      system FixLJ. FixJ is a transcriptional activator whose activity is dramatically
      enhanced by phosphorylation, whereas FixL is a hemoprotein kinase that controls
      the level of phosphorylated FixJ in response to oxygen availability. We have
      found that a mutant FixJ protein, FixJD54N, in which the presumed site of
      phosphorylation (aspartate 54) was changed to an asparagine, is strongly affected
      for phosphorylation by FixL and is not detectably phosphorylated from the low
      molecular-weight phosphate donor, acetyl-phosphate. Unexpectedly, FixL strongly
      enhances the transcriptional activity of the FixJD54N protein both in vivo and in
      vitro. We present evidence that FixJD54N transcriptional activity is enhanced by
      phosphorylation of an alternate residue in a reaction that requires FixL and ATP
      and is not affected by oxygen. We also demonstrate the key role of Asp-54 of FixJ
      in oxygen signal transduction.

PMID- 8144466
TI  - Competition between Vibrio fischeri strains during initiation and maintenance of
      a light organ symbiosis.
AB  - Colonization of the light-emitting organ of the Hawaiian squid Euprymna scolopes
      is initiated when the nascent organ of a newly hatched squid becomes inoculated
      with Vibrio fischeri cells present in the ambient seawater. Although they are
      induced for luminescence in the light organ, these symbiotic strains are
      characteristically non-visibly luminous (NVL) when grown in laboratory culture.
      The more typical visibly luminous (VL) type of V. fischeri co-occurs in Hawaiian
      seawater with these NVL strains; thus, two phenotypically distinct groups of this
      species potentially have access to the symbiotic niche, yet only the NVL ones are
      found there. In laboratory inoculation experiments, VL strains, when presented in
      pure culture, showed the same capability for colonizing the light organ as NVL
      strains. However, in experiments with mixed cultures composed of both VL and NVL
      strains, the VL ones were unable to compete with the NVL ones and did not persist
      within the light organ as the symbiosis became established. In addition, NVL
      strains entered light organs that had already been colonized by VL strains and
      displaced them. The mechanism underlying the symbiotic competitiveness exhibited
      by NVL strains remains unknown; however, it does not appear to be due to a higher
      potential for siderophore activity. While a difference in luminescence phenotype
      between VL and NVL strains in culture is not likely to be significant in the
      symbiosis, it has helped identify two distinct groups of V. fischeri that express
      different colonization capabilities in the squid light organ. This competitive
      difference provides a useful indication of important traits in light organ
      colonization.

PMID- 8144465
TI  - Gene expression in single cells of Bacillus subtilis: evidence that a threshold
      mechanism controls the initiation of sporulation.
AB  - Early during endospore formation in the bacterium Bacillus subtilis, two distinct
      cell types are formed. The initiation of this developmental pathway requires
      several physiological conditions (e.g., nutrient deprivation) and is controlled
      by the Spo0A transcription factor. We have found that in a culture of sporulating
      cells, there are two subpopulations, one that has initiated the developmental
      program and activated the expression of early developmental genes and one in
      which early developmental gene expression remains uninduced. We measured the
      expression of developmental (spo) genes in single cells of B. subtilis by using
      spo-lacZ fusions. Cells containing a spo-lacZ fusion were stained with a dye that
      fluoresces upon hydrolysis by beta-galactosidase, and the fluorescence in
      individual cells was measured with a flow cytometer. For Spo+ cells, we found
      that the proportion of the population expressing early developmental genes
      correlates well with the fraction of the population that eventually produces
      spores. In addition, mutations that cause a decrease in the amount of activated
      (phosphorylated) Spo0A transcription factor cause a decrease in the size of the
      subpopulation expressing early developmental genes that are directly activated by
      Spo0A approximately P. Again, the size of the subpopulation correlates well with
      the fraction of cells that produce spores. These results indicate that a
      threshold level of activated Spo0A (Spo0A approximately P) or of a component of
      the phosphorylation pathway must accumulate to induce sporulation gene expression
      and that most of the cells that are able to induce the expression of early genes
      that are directly activated by Spo0A approximately P go on to produce mature
      spores.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144467
TI  - Mutations which alter the kinetics of calcium transport alter the regulation of
      competence in Streptococcus pneumoniae.
AB  - In Streptococcus pneumoniae, Ca2+ induces a stress response which is regulated by
      a proteic activator known as competence factor (CF). This stress response is
      expressed as the induction of competence for DNA uptake and genetic
      transformation in exponentially growing cultures and by autolysis in late
      exponential phase. DNA transport during competence can be described as a
      homeostatic response that prevents autolysis of the cultures. Electrogenic and
      cooperative calcium transport with a Hill number (nH) of 2 appears to mediate
      this Ca2+ response. Mutant strains altered in their kinetics for Ca2+ transport,
      with nHs of 1 and 4, were isolated and characterized in order to address the role
      of the kinetics of Ca2+ transport in the Ca2+ response. The reduced cooperativity
      of Ca2+ uptake in mutant strain Cp2200 was associated with an absolute
      requirement for added CF to develop competence and with resistance to autolysis.
      The enhanced cooperativity of Ca2+ uptake in mutant strain Cp3300 was associated
      with facilitated competence and hypersensitivity to autolysis. Moreover, the
      mutation carried by strain Cp3300 increases the CF response of previously
      described competence-defective mutants. The pleiotropic mutants Cp2200 and Cp3300
      allowed us to demonstrate that cooperativity of transport determines the Ca2+
      response in S. pneumoniae.

PMID- 8144468
TI  - Detailed structural characterization of succinoglycan, the major
      exopolysaccharide of Rhizobium meliloti Rm1021.
AB  - The detailed structure of the symbiotically important exopolysaccharide
      succinoglycan from Rhizobium meliloti Rm1021 was determined by mass spectrometry
      with electrospray ionization and collision-induced dissociation of the octameric
      oligosaccharide repeating unit. Previously undetermined locations of the succinyl
      and acetyl modifications were determined, in respect to both residue locations
      within the octamer and the carbon positions within the pyranose ring. Glycosidic
      linkages determined previously by methylation analysis were also verified.

PMID- 8144469
TI  - Cloning and characterization of spoVR, a gene from Bacillus subtilis involved in
      spore cortex formation.
AB  - Screening for sigma E-dependent promoters led to the isolation of a gene from
      Bacillus subtilis, designated spoVR, which appears to be involved in spore cortex
      formation. Cultures of strains carrying mutations in spoVR had an increased
      proportion of phase-dark spores, which correlated with an increased proportion of
      cortexless spores seen by electron microscopy. The numbers of heat- and
      chloroform-resistant phase-bright spores produced by these mutants were decreased
      by about 3- to 10-fold, and accumulation of dipicolinate was decreased by more
      than 3-fold. The spoVR gene was located on the B. subtilis chromosome immediately
      upstream from, and in the opposite orientation of, the phoAIV gene. Expression of
      spoVR was initiated at the second hour of sporulation from a sigma E-dependent
      promoter, and this expression did not require any of the other known mother-cell
      specific transcriptional regulators. The spoVR gene was predicted to encode a
      product of 468 residues.

PMID- 8144470
TI  - Evidence that asgB encodes a DNA-binding protein essential for growth and
      development of Myxococcus xanthus.
AB  - The asg mutants of Myxococcus xanthus are defective in production of
      extracellular A-signal, which serves as a cell density signal for fruiting-body
      development. The DNA sequence of asgB, one of the three asg genes, was
      determined. The deduced amino acid sequence of AsgB contains a DNA-binding helix
      turn-helix motif near the C terminus. This putative helix-turn-helix is highly
      similar to the helix-turn-helix in region 4.2 of major sigma factors, which is
      the region that recognizes and interacts with -35 sequences of promoters. We
      propose that AsgB is a transcription factor that binds to DNA sequences similar
      to the -35 hexamer, TTGACA. Analyses of asgB RNA levels and expression of an asgB
      lacZ translational fusion indicate that expression of asgB remains fairly
      constant during the transition from growth into early development. The mutation
      within the asgB480 allele was identified as an A-to-G transition that results in
      a threonine-to-alanine substitution in the predicted protein product. Attempts to
      replace the wild-type copy of asgB with a null allele failed, indicating that
      asgB may be essential for growth.

PMID- 8144471
TI  - Rhizobium meliloti contains a novel second homolog of the cell division gene
      ftsZ.
AB  - We have identified a second homolog of the cell division gene, ftsZ, in the
      endosymbiont Rhizobium meliloti. The ftsZ2 gene was cloned by screening a genomic
      lambda library with a probe derived from PCR amplification of a highly conserved
      domain. It encodes a 36-kDa protein which shares a high level of sequence
      similarity with the FtsZ proteins of Escherichia coli and Bacillus subtilis and
      FtsZ1 (Z1) of R. meliloti but lacks the carboxy-terminal region conserved in
      other FtsZ proteins. The identity of the ftsZ2 gene product was confirmed both by
      in vitro transcription-translation in an R. meliloti S-30 extract and by
      overproduction in R. meliloti cells. As with Z1, the overproduction of FtsZ2 in
      E. coli inhibited cell division and induced filamentation, although to a lesser
      extent than with Z1. However, the expression of ftsZ2 in E. coli under certain
      conditions caused some cells to coil dramatically, a phenotype not observed
      during Z1 overproduction. Although several Tn3-GUS (glucuronidase) insertions in
      a plasmid-borne ftsZ2 gene failed to cross into the chromosome, one interruption
      in the chromosomal ftsZ2 gene was isolated, suggesting that ftsZ2 is nonessential
      for viability. The two ftsZ genes were genetically mapped to the R. meliloti main
      chromosome, approximately 100 kb apart.

PMID- 8144472
TI  - Isolation and characterization of a regulatory gene affecting rhamnolipid
      biosurfactant synthesis in Pseudomonas aeruginosa.
AB  - A mutant strain (65E12) of Pseudomonas aeruginosa that is unable to produce
      rhamnolipid biosurfactants and lacks rhamnosyltransferase activity was
      genetically complemented by using a P. aeruginosa PG201 wild-type gene library. A
      single complementing cosmid was isolated on the basis of surface tension
      measurements of subcultures of the transconjugants by using a sib selection
      strategy. The subcloning of the complementing cosmid clone yielded a 2-kb
      fragment capable of restoring rhamnolipid biosynthesis, rhamnosyltransferase
      activity, and utilization of hexadecane as a C source in mutant 65E12. The
      nucleotide sequence of the complementing 2-kb fragment was determined, and a
      single open reading frame (rhlR) of 723 bp specifying a putative 28-kDa protein
      (RhlR) was identified. Sequence homologies between the RhlR protein and some
      regulatory proteins such as LasR of P. aeruginosa, LuxR of Vibrio fischeri, RhiR
      of Rhizobium leguminosarum, and the putative activator 28-kDa UvrC of Escherichia
      coli suggest that the RhlR protein is a transcriptional activator. A putative
      target promoter which is regulated by the RhlR protein has been identified 2.5 kb
      upstream of the rhlR gene. Multiple plasmid-based rhlR gene copies had a
      stimulating effect on the growth of the P. aeruginosa wild-type strain in
      hexadecane-containing minimal medium, on rhamnolipid production, and on the
      production of pyocyanin chromophores. Disruption of the P. aeruginosa wild-type
      rhlR locus led to rhamnolipid-deficient mutant strains, thus confirming directly
      that this gene is necessary for rhamnolipid biosynthesis. Additionally, such
      PG201::'rhlR' mutant strains lacked elastase activity, indicating that the RhlR
      protein is a pleiotropic regulator.

PMID- 8144473
TI  - Locations of genetic markers on the physical map of the chromosome of Neisseria
      gonorrhoeae FA1090.
AB  - To increase the utility of the previously constructed physical map of the
      chromosome of Neisseria gonorrhoeae FA1090, 28 additional genetic markers were
      localized on the map. Cloned gonococcal genes were used to probe Southern blots
      of restriction enzyme-digested DNA separated on pulsed-field gels, thus
      identifying the fragment in each of several digests to which the probe hybridized
      and the map location of each gene. The addition of the new markers brings the
      total number of mapped loci for this strain to 68; the locations of all of those
      markers on the updated map are shown.

PMID- 8144474
TI  - Role for 10Sa RNA in the growth of lambda-P22 hybrid phage.
AB  - Certain lambda-P22 hybrids, providing that they express the P22 C1 protein, fail
      to grow in Escherichia coli with the sipB391 mutation. We show that sipB391,
      previously located to the 57-min region of the E. coli chromosome, is a large
      deletion that extends into the 3' end of ssrA, a gene encoding the small stable
      10Sa RNA. This deletion, apparently created by the excision of a cryptic
      prophage, CP4-57 (identified by Kirby et al. [J. E. Kirby, J. E. Trempy, and S.
      Gottesman, J. Bacteriol. 176:2068-2081]), leaves most of ssrA intact but removes
      the sequence encoding the 3' end of the precursor form of 10Sa RNA. The lack of
      functional 10Sa RNA, resulting from either the excision of CP4-57 or insertional
      inactivation of ssrA, appears to be responsible for the inhibition of lambda-P22
      growth in E. coli with the sipB391 mutation. We propose that 10Sa RNA acts either
      directly or indirectly to facilitate removal of C1 protein from its DNA target
      site.

PMID- 8144475
TI  - Development of a gene cloning system for Streptomyces hygroscopicus subsp.
      yingchengensis, a producer of three useful antifungal compounds, by elimination
      of three barriers to DNA transfer.
AB  - Streptomyces hygroscopicus 10-22 could not be transformed with any of the
      commonly used Streptomyces plasmid vectors and was resistant to plaque formation
      by the Streptomyces phages phi C31 and R4. Repeated selection resulted in the
      isolation of derivatives of S. hygroscopicus 10-22 that could be transformed with
      pIJ101- and pJV1-derived cloning vectors and of restriction-deficient derivatives
      that could accept DNA propagated in Streptomyces lividans 66. These new strains,
      which include three that still produce the original antibiotics, can be used as
      hosts for gene cloning. Insertion of nonreplicating vectors by homologous
      recombination and transposition of Tn4560 were demonstrated in S. hygroscopicus
      10-22.

PMID- 8144476
TI  - Characterization of phi HAU3, a broad-host-range temperate streptomyces phage,
      and development of phasmids.
AB  - phi HAU3 is a temperate Streptomyces phage with cohesive ends and a broad host
      range that includes Streptomyces hygroscopicus 10-22, a producer of antifungal
      compounds, but it fails to grow on Streptomyces lividans 66. Two phasmid
      derivatives were constructed that function as lambda cosmid vectors in
      Escherichia coli and as phages in Streptomyces spp.

PMID- 8144477
TI  - Riboflavin synthesis genes are linked with the lux operon of Photobacterium
      phosphoreum.
AB  - Four genes immediately downstream of luxG in the Photobacterium phosphoreum lux
      operon (ribEBHA) have been sequenced and shown to be involved in riboflavin
      synthesis. Sequence analyses and complementation of Escherichia coli riboflavin
      auxotrophs showed that the gene products of ribB and ribA are 3,4-dihydroxy-2
      butanone 4-phosphate (DHBP) synthetase and GTP cyclohydrolase II, respectively.
      By expression of P. phosphoreum ribE in E. coli using the bacteriophage T7
      promoter-RNA polymerase system, ribE was shown to code for riboflavin synthetase,
      which catalyzes the conversion of lumazine to riboflavin. Increased thermal
      stability of RibE on expression with RibH indicated that ribH coded for lumazine
      synthetase. The organization of the rib genes in P. phosphoreum is quite
      distinct, with ribB and ribA being linked but separated by ribH, whereas in E.
      coli, they are unlinked and in Bacillus subtilis, RibB and RibA functions are
      coded by a single gene.

PMID- 8144478
TI  - Autoradiographic study of hyphal growth during aerial mycelium development in
      Streptomyces antibioticus.
AB  - The pattern of growth of aerial mycelium in Streptomyces species was investigated
      by autoradiography. Colonies of Streptomyces antibiotics were labeled with N
      acetyl-D-[1-3H] glucosamine to localize the sites of hyphal growth during the
      development of aerial mycelium. Autoradiographs obtained with sections of the
      colonies revealed that hyphal growth occurs not only at the top of the colony but
      also in the inner zones of the aerial mycelium.

PMID- 8144479
TI  - Inducible amber suppressor for Bacillus subtilis.
AB  - An amber suppressor variant of Bacillus subtilis tyrosyl-tRNA was constructed and
      placed under control of the isopropyl-beta-D-thiogalactopyranoside (IPTG)
      inducible Pspac promoter. Addition of IPTG resulted in a 50-fold increase in the
      expression of an rpsD-lacZ fusion containing a UAG amber codon. This system
      permitted isolation of a conditional lethal mutant which required IPTG for
      growth.

PMID- 8144480
TI  - Heat inactivation of Bacillus subtilis spores lacking small, acid-soluble spore
      proteins is accompanied by generation of abasic sites in spore DNA.
AB  - Previous work has shown that lethal heat treatment of Bacillus subtilis spores
      lacking the major DNA-binding proteins SASP-alpha and -beta (alpha-beta- spores)
      causes significant DNA damage, including many single-strand breaks. In this work
      we have used a reagent specific for aldehydes present in abasic sites in DNA to
      show that DNA from wild-type spores killed by heat treatment to levels of < 0.05%
      survival had at most two aldehydes (i.e., abasic sites) per 10(4) nucleotides,
      while DNA from alpha(-)beta- spores killed to similar levels had 7 to 20 times as
      many abasic sites per 10(4) nucleotides. These data were generally consistent
      with the level of single-strand breaks in DNA from these heated spores and
      strongly suggest that a major mechanism responsible for the heat killing of
      alpha(-)beta- (but not wild-type) spores is DNA depurination followed by strand
      breakage at the resultant abasic site. In contrast, hydrogen peroxide killing of
      alpha(-)beta - spores was not accompanied by generation of a high level of DNA
      aldehydes.

PMID- 8144481
TI  - Transposition of IS2 into the hemB gene of Escherichia coli K-12.
AB  - Genetic studies of the hemB gene in Escherichia coli have resulted in the
      recovery of both stable and unstable mutant strains. The stable strains have been
      shown to result from large deletions. This study demonstrates that unstable
      strains result from the insertion of transposable element IS2 primarily into the
      5' region of the structural gene; the instability results from precise excision
      of the element, producing strains with both high and low frequencies of
      reversion. This first report of IS2 insertion into hemB suggests that this gene
      may be a preferred target for insertion of this transposable element.

PMID- 8144482
TI  - Efficient degradation of trichloroethylene by a hybrid aromatic ring dioxygenase.
AB  - Engineering of hybrid gene clusters between the toluene metabolic tod operon and
      the biphenyl metabolic bph operon greatly enhanced the rate of biodegradation of
      trichloroethylene. Escherichia coli cells carrying a hybrid gene cluster composed
      of todC1 (the gene encoding the large subunit of toluene terminal dioxygenase in
      Pseudomonas putida F1), bphA2 (the gene encoding the small subunit of biphenyl
      terminal dioxygenase in Pseudomonas pseudoalcaligenes KF707), bphA3 (the gene
      encoding ferredoxin in KF707), and bphA4 (the gene encoding ferredoxin reductase
      in KF707) degraded trichloroethylene much faster than E. coli cells carrying the
      original toluene dioxygenase genes (todC1C2BA) or the original biphenyl
      dioxygenase genes (bphA1A2A3A4).

PMID- 8144483
TI  - Fibrillarin-like proteins occur in the domain Archaea.
AB  - Fibrillarin is found in the nucleolus of Eucarya and associated with small
      nucleolar RNAs. It is involved in the processing of precursor rRNA. Two genes,
      encoding fibrillarin-like proteins from Methanococcus voltae and Methanococcus
      vannielii, have been isolated. The genes were named flpA (fibrillarin-like
      protein).

PMID- 8144484
TI  - Use of transcriptional fusions to monitor gene expression: a cautionary tale.
AB  - Gene fusions are frequently used to facilitate studies of gene expression and
      promoter activity. We have found that certain reporter genes can, themselves,
      influence promoter activity. For example, the commonly used luxAB reporter genes
      can activate or repress transcription from a subset of promoters, generating data
      apparently at odds with those obtained with other reporter genes. These effects
      are probably related to an intrinsically curved DNA segment in the 5' coding
      sequence of the luxA gene. Thus, caution must be observed when one is
      interpreting results obtained with a single reporter gene system such as luxAB.

PMID- 8144485
TI  - Reconstruction of glucose uptake and phosphorylation in a glucose-negative mutant
      of Escherichia coli by using Zymomonas mobilis genes encoding the glucose
      facilitator protein and glucokinase.
AB  - Expression of the Zymomonas mobilis glf (glucose facilitator protein) and glk
      (glucokinase) genes in Escherichia coli ZSC113 (glucose negative) provided a new
      functional pathway for glucose uptake and phosphorylation. Both genes were
      essential for the restoration of growth in glucose minimal medium and for acid
      production on glucose-MacConkey agar plates.

PMID- 8144486
TI  - Bacterial transport systems.

PMID- 8144487
TI  - Transport across the bacterial outer membrane.
AB  - Diffusion of small molecules across the outer membrane of gram-negative bacteria
      may occur through protein channels and through lipid bilayer domains. Among
      protein channels, many examples of trimeric porins, which produce water-filled
      diffusion channels, are known. Although the channels are nonspecific, the
      diffusion rates of solutes are often drastically affected by their gross
      physicochemical properties, such as size, charge, or lipophilicity, because the
      channel has a dimension not too different from that of the diffusing solutes. In
      the last few years, the structures of three such porins have been solved by X-ray
      crystallography. It is now known that a monomer unit traverses the membrane 16
      times as beta-strands, and one of the external loop folds back into the channel
      to produce a narrow constriction. Most of the static properties of the channel,
      such as the pore size and the position of the amino acids that produce the
      constriction, can now be explained by the three-dimensional structure.
      Controversy, however, still surrounds the issue of whether there are dynamic
      modulation of the channel properties in response to pH, ionic strength, or
      membrane potential, and of whether such responses are physiological. More
      recently, two examples of monomeric porins have been identified. These porins
      allow a very slow diffusion of solutes, but the reason for this low permeability
      is still unclear. Finally, channels with specific binding sites facilitate the
      diffusion of specific classes of nutrients, often those compounds that are too
      large to penetrate rapidly through the porin channels.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8144488
TI  - TonB protein and energy transduction between membranes.
AB  - TonB protein couples cytoplasmic membrane electrochemical potential to active
      transport of iron-siderophore complexes and vitamin B12 through high-affinity
      outer membrane receptors of Gram-negative bacteria. The mechanism of energy
      transduction remains to be determined, but important concepts have already begun
      to emerge. Consistent with its function, TonB is anchored in the cytoplasmic
      membrane by its uncleaved amino terminus while largely occupying the periplasm.
      Both the connection to the cytoplasmic membrane and the amino acid sequences of
      the anchor are essential for activity. TonB directly associates with a number of
      envelope proteins, among them the outer membrane receptors and cytoplasmic
      membrane protein ExbB. ExbB and TonB interact through their respective
      transmembrane domains. ExbB is proposed to recycle TonB to an active conformation
      following energy transduction to the outer membrane. TonB most likely associates
      with the outer membrane receptors through its carboxy terminus, which is required
      for function. In contrast, the novel proline-rich region of TonB can be deleted
      without affecting function. A model that incorporates this information, as well
      as tempered speculation, is presented.

PMID- 8144489
TI  - Mechanisms of TonB-catalyzed iron transport through the enteric bacterial cell
      envelope.
AB  - The recent solution of enteric bacterial porin structure, and new insights into
      the mechanism by which outer membrane receptor proteins recognize and internalize
      specific ligands, advocates the re-evaluation of TonB-dependent transport
      physiology. In this minireview we discuss the potential structural features of
      siderophore receptors and TonB, and use this analysis to evaluate both existing
      and new models of energy and signal transduction from the inner membrane to the
      outer membrane of gram-negative bacteria.

PMID- 8144490
TI  - The Escherichia coli mannitol permease as a model for transport via the bacterial
      phosphotransferase system.
AB  - The bacterial phosphoenolpyruvate-dependent carbohydrate phosphotransferase
      system (PTS) consists of several proteins whose primary functions are to
      transport and phosphorylate their substrates. The complexity of the PTS
      undoubtedly reflects its additional roles in chemotaxis to PTS substrates and in
      regulation of other metabolic processes in the cell. The PTS permeases (Enzymes
      II) are the membrane-associated proteins of the PTS that sequentially recognize,
      transport, and phosphorylate their specific substrates in separate steps, and the
      Escherichia coli mannitol permease is one of the best studied of these proteins.
      It consists of two cytoplasmic domains (EIIA and EIIB) involved in mannitol
      phosphorylation and an integral membrane domain (EIIC) which is sufficient to
      bind mannitol, but which transports mannitol at a rate that is dependent on
      phosphorylation of the EIIA and EIIB domains. Recent results show that several
      residues in a hydrophilic, 85-residue segment of the EIIC domain are important
      for the binding, transport, and phosphorylation of mannitol. This segment may be
      at least partially exposed to the cytoplasm of the cell. A model is proposed in
      which this region of the EIIC domain is crucial in coupling phosphorylation of
      the EIIB domain to transport through the EIIC domain of the mannitol permease.

PMID- 8144491
TI  - What's new with lactose permease.
AB  - The lactose permease of Escherichia coli is a paradigm for polytopic membrane
      transport proteins that transduce free energy stored in an electrochemical ion
      gradient into work in the form of a concentration gradient. Although the permease
      consists of 12 hydrophobic transmembrane domains in probable alpha-helical
      conformation that traverse the membrane in zigzag fashion connected by
      hydrophilic "loops", little information is available regarding the folded
      tertiary structure of the molecule. In a recent approach site-directed
      fluorescence labeling is being used to study proximity relationships in lactose
      permease. The experiments are based upon site-directed pyrene labeling of
      combinations of paired Cys replacements in a mutant devoid of Cys residues. Since
      pyrene exhibits excimer fluorescence if two molecules are within about 3.5A, the
      proximity between paired labeled residues can be determined. The results
      demonstrate that putative helices VIII and IX are close to helix X. Taken
      together with other findings indicating that helix VII is close to helices X and
      XI, the data lead to a model that describes the packing of helices VII to XI.

PMID- 8144492
TI  - The family of organo-phosphate transport proteins includes a transmembrane
      regulatory protein.
AB  - This review article briefly summarizes aspects of our current understanding of
      the Uhp sugar phosphate transport system in enteric bacteria, particularly the
      mode of genetic regulation of its synthesis. This regulation occurs by a process
      that involves an example of the very widespread and ever-growing group of so
      called two-component bacterial regulatory systems, a mechanism of response to
      environmental signals that employs phosphate transfer reactions between
      constituent proteins. Of emphasis here is the unusual involvement in
      transmembrane signaling of the UhpC protein which is related in sequence and
      structure to some transport proteins, including the very protein whose synthesis
      it helps regulate.

PMID- 8144494
TI  - Evidence for three different electrophoretic pathways in yeast mitochondria: ion
      specificity and inhibitor sensitivity.
AB  - We identified three electrophoretic pathways by spectrophotometrically following
      the swelling of isolated yeast mitochondria: An anion uniport whose activity
      could only be detected after depletion of divalent cations from the matrix by
      treatment with 1,10-phenanthroline. This uniport was inhibited by Mg2+ and
      dicyclohexylcarbodiimide. A K+ (Na+) uniport which was detected only when
      mitochondria were suspended at low pH and low temperature. This uniport was
      sensitive to ruthenium red and oleic acid. A K+ selective uniport which was
      activated by alkaline pH and ATP depletion. This pathway was sensitive to
      glibenclamide and to various amphiphilic cations. Similarities and differences
      between these three electrophoretic pathways and the electrophoretic systems
      described in mammalian and plant mitochondria are discussed.

PMID- 8144495
TI  - The TF1-ATPase and ATPase activities of assembled alpha 3 beta 3 gamma, alpha 3
      beta 3 gamma delta, and alpha 3 beta 3 gamma epsilon complexes are stimulated by
      low and inhibited by high concentrations of rhodamine 6G whereas the dye only
      inhibits the alpha 3 beta 3, and alpha 3 beta 3 delta complexes.
AB  - The ATPase activity of the F1-ATPase from the thermophilic bacterium PS3 is
      stimulated at concentrations of rhodamine 6G up to about 10 microM where 70%
      stimulation is observed at 36 degrees C. Half maximal stimulation is observed at
      about 3 microM dye. At rhodamine 6G concentrations greater than 10 microM, ATPase
      activity declines with 50% inhibition observed at about 75 microM dye. The ATPase
      activities of the alpha 3 beta 3 gamma and alpha 3 beta 3 gamma delta complexes
      assembled from isolated subunits of TF1 expressed in E. coli deleted of the unc
      operon respond to increasing concentrations of rhodamine 6G nearly identically to
      the response of TF1. In contrast, the ATPase activities of the alpha 3 beta 3 and
      alpha 3 beta 3 delta complexes are only inhibited by rhodamine 6G with 50%
      inhibition observed, respectively, at 35 and 75 microM dye at 36 degrees C. The
      ATPase activity of TF1 is stimulated up to 4-fold by the neutral detergent, LDAO.
      In the presence of stimulating concentrations of LDAO, the ATPase activity of TF1
      is no longer stimulated by rhodamine 6G, but rather, it is inhibited with 50%
      inhibition observed at about 30 microM dye at 30 degrees C. One interpretation of
      these results is that binding of rhodamine 6G to a high-affinity site on TF1
      stimulates ATPase activity and unmasks a low-affinity, inhibitory site for the
      dye which is also exposed by LDAO.

PMID- 8144496
TI  - Inhibition of membrane-bound succinate dehydrogenase by fluorescamine.
AB  - Fluorescamine rapidly inactivated membrane-bound succinate dehydrogenase. The
      inhibition of the enzyme by this reagent was prevented by succinate and malonate,
      suggesting that the group modified by fluorescamine was located at the active
      site. The modification of the active site sulfhydryl group by 5,5'-dithiobis(2
      nitrobenzoic acid) (DTNB) did not alter the inhibitory action of fluorescamine.
      However, the protective effect of malonate against fluorescamine inhibition was
      abolished in the enzyme modified at the thiol.

PMID- 8144493
TI  - Na+/H+ antiporters, molecular devices that couple the Na+ and H+ circulation in
      cells.
AB  - Na+/H+ antiporters are universal devices involved in the Na+ and H+ circulation
      of both eukaryotes and prokaryotes, thus playing an essential role in the pH and
      Na+ homeostasis of cells. This review focuses on the major impact of the
      application of molecular biology tools in the study of the antiporters. These
      tools permit the verification of the role of the antiporters and provide insights
      into their unique biology. A novel signal transduction to Na+ involving nhaR, a
      positive regulator, controls the expression of nhaA in E. coli. A "pH sensor"
      regulates the activity of Na+/H+ antiporters, both in eukaryotes and prokaryotes.
      A most intricate signal transduction to pH involving phosphorylation steps
      controls the activity of nhel in higher mammals. The identification of Histidine
      226 in the "pH sensor" of NhaA is a step forward towards the understanding of the
      pH regulation of these proteins.

PMID- 8144497
TI  - The cysteine-rich region of raf-1 kinase contains zinc, translocates to
      liposomes, and is adjacent to a segment that binds GTP-ras.
AB  - Different domains of the serine/threonine kinase, raf-1, were expressed as fusion
      proteins with glutathione S-transferase (GST) in Escherichia coli and purified to
      near homogeneity by affinity chromatography. A cysteine-rich domain of raf-1 was
      found to contain 2 mol of zinc (molar basis), similar to analogous cysteine-rich
      domains of protein kinase C. GST-fusion proteins, containing the cysteine-rich
      domain of raf-1, bound to liposomes in a phosphatidylserine-dependent manner. In
      contrast to protein kinase C, the translocation of raf-1 was not dependent upon
      diacylglycerol, phorbol ester, or calcium, nor did raf-1 bind phorbol esters. A
      GST-fusion protein encoding residues 1-147 of raf-1 bound to normal GTP-ras with
      high affinity, but not to mutant GTP-Ala35 ras; no binding was detected to GDP
      ras. The binding of a smaller fusion protein (residues 1-130 of raf-1) was about
      10-fold weaker, inferring that a 17-amino acid sequence represents a critical
      binding determinant in intact raf-1. These residues are adjacent to the amino
      terminal end of, and partially extend into, the cysteine-rich domain (amino acids
      139-184). A synthetic peptide corresponding to this 17-amino acid sequence
      blocked the interaction of raf-1 with ras. The function of the cysteine-rich
      region of raf-1 homologous to protein kinase C is to promote translocation of raf
      1 kinase to membranes and to form part of the high affinity binding site for GTP
      ras.

PMID- 8144498
TI  - Characterization of a novel high molecular mass protein with peptidase activity
      purified from the human erythrocyte membrane by calmodulin affinity
      chromatography.
AB  - A previously undescribed high molecular mass protein (HMP) from human erythrocyte
      membranes was solubilized by Triton X-100 and purified on a calmodulin-agarose
      column in the presence of Ca2+. It was shown to have a native molecular mass of
      522-560 kDa, comprised of a single subunit of a molecular mass of 28 kDa (p28).
      The protein is associated with the lipid bilayer rather than with the
      cytoskeletal component of the membrane. The purified HMP showed peptidase
      hydrolyzing activity toward substrates containing hydrophobic amino acids at the
      P1 position of the P2-P1 cleavage site. The activity was inhibited by serine
      proteinase inhibitors (leupeptin, phenylmethansulfonyl fluoride) and chymotrypsin
      inhibitors in particular (chymostatin, N-tosyl-L-phenylalanine chloromethyl
      ketone). The enzyme exhibited maximal activity at slightly alkaline pH (7.5-8.5)
      and at 37 degrees C and was stimulated over a narrow range of SDS concentrations
      (maximal at 0.05%). HMP was found to cross-react in Western blots with an
      antibody raised against the rabbit multicatalytic proteinase. The single subunit
      of HMP therefore contains both the catalytic activity and a sequence necessary
      for its association into a multimeric complex. The properties of the human
      erythrocyte membrane HMP described indicate that it is a novel peptidase related
      to the ubiquitous multicatalytic proteinase.

PMID- 8144499
TI  - Cytosine 73 is a discriminator nucleotide in vivo for histidyl-tRNA in
      Escherichia coli.
AB  - The acceptor helix of histidine tRNAs in Escherichia coli is capped by a unique
      base pair in which the cytosine at the discriminator position is paired with an
      extra guanosine at -1. In previous in vitro studies, the presence of the G-1:C73
      base pair was found to be required to obtain both optimal histidylation by
      histidyl-tRNA synthetase and accurate 5' processing by RNase P. We investigated
      the role of G-1:C73 in histidine tRNA identity and found that nucleotide
      substitutions conferred mischarging by other amino acids in a pattern that
      correlated with the discriminator base and not with the extra nucleotide at -1.
      As shown by primer extension experiments, the relatively minor role of the -1
      nucleotide in vivo could be attributed to altered RNase P processing. These
      studies show that interactions of tRNAs in vivo both with RNase P during tRNA
      biosynthesis and with the pool of aminoacyl-tRNA synthetases can modulate the
      effects of substitutions at recognition nucleotides, eliciting changes in
      transfer RNA identity.

PMID- 8144500
TI  - Cloning and expression of cDNA for a new type of Gal beta 1,3GalNAc alpha 2,3
      sialyltransferase.
AB  - Based on the sequences of the highly conserved segments in the previously cloned
      sialyltransferases, a cDNA encoding a new type of Gal beta 1,3GalNAc alpha 2,3
      sialyltransferase (ST3GalA.2) has been isolated from both mouse and rat brain
      cDNA libraries. The cDNA sequences included an open reading frame coding for 350
      amino acids, and the primary structure of this enzyme suggested a putative domain
      structure consisting of four regions, like that in other glycosyltransferases.
      The deduced amino acid sequence of ST3GalA.2 (mouse) showed 76% identity in the
      active domain with that of the previously cloned mouse Gal beta 1,3GalNAc alpha
      2,3-sialyltransferase (ST3GalA.1 (Lee, Y.-C., Kurosawa, N., Hamamoto, T.,
      Nakaoka, T., and Tsuji, S. (1993) Eur. J. Biochem. 216, 377-385)). Northern
      blotting indicated that the expression of ST3GalA.2 mRNA is tissue-specific, it
      being prominent in brain and liver, while that in the other tissues is very low.
      This enzyme expressed in COS-7 cells exhibited transferase activity only toward
      the disaccharide moiety of Gal beta 1,3GalNAc of glycolipids as well as
      glycoproteins and oligosaccharides like ST3GalA.1, but showed a difference in
      acceptor substrate preference, i.e. asialo-GM1 and GM1 were much more suitable
      substrates for ST3GalA.2 than for ST3GalA.1.

PMID- 8144501
TI  - Identification of the amino acids involved in the functional interaction between
      photosystem I and ferredoxin from Synechocystis sp. PCC 6803 by chemical cross
      linking.
AB  - Ferredoxin isolated from the cyanobacterium Synechocystis sp. PCC 6803 has been
      chemically cross-linked to purified photosystem I from the same organism. The
      reaction was catalyzed by N-ethyl-3-(3-dimethylaminopropyl)carbodiimide in the
      presence of N-hydroxysulfosuccinimide. A short reaction time and neutral pH
      values can be used in the presence of the two reagents, ensuring the integrity of
      both of the proteins and the iron-sulfur cluster of the ferredoxin. The only
      covalent complex detected comprised ferredoxin and the photo-system I (PSI)-D
      subunit, as identified by antibodies probing after electrophoresis. Electron
      paramagnetic resonance measurements of this covalent complex have shown that the
      cross-linked ferredoxin was entirely photoreducible by photosystem I and that the
      molar ratio of ferredoxin to PSI was close to 1. Extensive sequencing of the
      peptides obtained after proteolysis of the purified cross-linked product led to
      the identification of a covalent bond between glutamic acid 93 of ferredoxin and
      lysine 106 of the PSI-D subunit.

PMID- 8144502
TI  - Transient DNA demethylation in differentiating mouse myoblasts correlates with
      higher activity of 5-methyldeoxycytidine excision repair.
AB  - It has been recently shown that in developing chicken embryonic nuclear extracts
      there is a 5-methyldeoxycytidine excision repair activity (Jost, J. P. (1993)
      Proc. Natl. Acad. Sci. U. S. A. 90, 4684-4688). We show that in differentiating
      mouse myoblasts, a similar enzymatic reaction may be responsible for the genome
      wide DNA demethylation (up to 50% of all CmCGG) occurring between the 3rd and 5th
      days of differentiation. Furthermore, in differentiating myoblasts, there is
      first a 50% transient decrease in DNA methyltransferase activity and a 90% drop
      in the rate of DNA synthesis, followed by an increase in 5-methyl-CpG
      endonuclease and 5-methyldeoxycytidine excision repair activities. As tested in
      vitro, the maximal activity of the 5-methyldeoxycytidine excision repair
      coincides with the maximal in vivo genome-wide DNA demethylation. We also find
      that 3-aminobenzamide, a potent inhibitor of ADP-ribosyltransferase, blocks the
      differentiation of myoblasts, the 5-methyldeoxycytidine excision repair activity,
      and the genome-wide demethylation.

PMID- 8144503
TI  - Zeta PKC plays a critical role during stromelysin promoter activation by platelet
      derived growth factor through a novel palindromic element.
AB  - Stromelysin is a metalloproteinase with the widest substrate specificity that
      plays a critical role in the induction of the metastatic phenotype in cancer
      cells. The mechanisms whereby growth factors and oncogenes control stromelysin
      expression are beginning to be characterized. We have recently demonstrated that
      protein kinase C isotypes down-regulatable by chronic exposure to phorbol esters
      are not involved in stromelysin gene expression in response to platelet-derived
      growth factor, ras oncogene, and phosphatidylcholine-hydrolyzing phospholipase C.
      We also identified a region in the stromelysin promoter, distinct from the 12-O
      tetradecanoylphorbol-13-acetate-responsive element, responsible for the promoter
      activity in response to these stimulants. In this paper, we further characterize
      that promoter fragment and demonstrate that the region encompassing nucleotides 
      1218 to -1202, including the palindromic sequence ACTAGT, is necessary and
      sufficient for the control of stromelysin gene expression. The involvement of
      zeta-protein kinase C but not of c-raf in the stimulation of stromelysin promoter
      activity in response to platelet-derived growth factor is also demonstrated here.
      All these data suggest the existence of a bifurcation downstream of ras in the
      signaling mechanisms leading to stromelysin expression and DNA synthesis.

PMID- 8144504
TI  - Factor-dependent transcription termination by vaccinia RNA polymerase. Kinetic
      coupling and requirement for ATP hydrolysis.
AB  - Transcription termination during synthesis of vaccinia early mRNAs occurs
      downstream of a UUUUUNU signal in the nascent transcript and requires a virus
      encoded termination factor (VTF), which is identical with the vaccinia mRNA
      capping enzyme. Using purified transcription complexes halted at defined sites on
      linear DNA templates, we have examined the order and timing of events during a
      single round of elongation and termination. We find that although cap synthesis
      occurs by the time the nascent RNA is 31 nucleotides long, capping enzyme is not
      stably associated with the elongation complex at this stage. Stable interaction,
      defined by the formation of a termination-competent complex, requires a longer
      nascent RNA, e.g. 51 nucleotides, but does not depend on prior transcription of
      the termination signal. The acquisition of termination competence correlates
      temporally with the physical association of capping enzyme/VTF with the
      elongation complex, as revealed by UV cross-linking of the capping enzyme large
      subunit to the nascent RNA chain. Subsequent induction of termination and
      transcript release by capping enzyme requires energy, specifically the hydrolysis
      of ATP. The choice of termination site is flexible and is determined by a kinetic
      balance between the rate of polymerase elongation and the rate of signaling.
      Signaling rate is related directly to the concentration of hydrolyzable ATP. An
      apparent lower limit of 33 nucleotides between the 5' boundary of the termination
      signal and the most proximal termination site implies that the UUUUUNU signal
      must be extruded from the RNA polymerase before it can be acted upon by VTF.
      Similarities between VTF-dependent termination and rho-dependent termination
      underscore an evolutionarily conserved mechanism for RNA signal transduction to
      the elongating RNA polymerase.

PMID- 8144505
TI  - Intramolecular charge heterogeneity in purified major histocompatibility class II
      alpha and beta polypeptide chains.
AB  - Major histocompatibility (MHC) class II antigens are heterodimeric cell surface
      glycoproteins consisting of an alpha and a beta chain. Although one-dimensional
      SDS-polyacrylamide gel electrophoresis analysis of purified MHC class II antigens
      shows a single diffuse band for each chain, multiple spots of identical molecular
      size were observed for each chain when analyzed by two-dimensional
      electrophoresis. The basis of this heterogeneity has not been clearly defined and
      has been predicted partially to be due to glycosylation and/or phosphorylation of
      the mature protein. To investigate the role of the three N-linked
      oligosaccharides of the alpha and beta chains in determining the isoelectric
      point of each chain, affinity-purified MHC class II antigens from human and rat
      sources were deglycosylated using asparagine amidase. The complete enzymatic
      removal of all three N-linked oligosaccharides was confirmed by SDS
      polyacrylamide gel electrophoresis as well as by four different lectin-linked
      Western blot analyses. Two-dimensional gel analysis of the deglycosylated
      molecules shows no significant difference from the fully glycosylated chains. We
      have expressed truncated forms of the HLA DR2 chains which lack the transmembrane
      and cytoplasmically exposed regions in Escherichia coli. Two-dimensional
      electrophoresis of these single chains also reveal multiple banding patterns. The
      two-dimensional banding patterns described are unaffected by exposure to acidic
      or basic conditions, increased gel running time in the first dimension, treatment
      of the proteins with alkaline phosphatase to remove any potential
      phosphorylation, or preincubation in the presence of iodoacetamide. Multiple
      forms of recombinant alpha and beta chains were also observed in Tris-glycine
      urea gels which merged into a single band in the presence of SDS. In addition,
      partially fractionated bands from preparative isoelectric focusing gels, when
      refocused, showed an identical number of multiple spots spanning the same range
      of isoelectric points. These results together suggest that each polypeptide chain
      of MHC class II antigens may exist in multiconformational forms, and the observed
      charge heterogeneity is independent of glycosylation and phosphorylation of the
      proteins.

PMID- 8144506
TI  - Regulation of cholesterol 7 alpha-hydroxylase gene expression in Hep-G2 cells.
      Effect of serum, bile salts, and coordinate and noncoordinate regulation with
      other sterol-responsive genes.
AB  - Regulation of cholesterol 7 alpha-hydroxylase mRNA level in Hep-G2 cells was
      studied and compared with that of two other sterol-responsive genes, those for
      the low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase. In culture medium containing 10% fetal bovine
      serum (complete medium) for up to 24 h, the mRNA for cholesterol 7 alpha
      hydroxylase gradually increased to 2-fold of the time 0 control. Culture of Hep
      G2 cells in serum-free medium for 24 h resulted in stimulation of mRNA levels for
      LDL receptor (5-fold) and HMG-CoA reductase (6-fold). Surprisingly, the mRNA
      level for cholesterol 7 alpha-hydroxylase also increased 5-fold at 8 h and 4-fold
      at 24 h compared with the time 0 control. The addition of beta-migrating very low
      density lipoprotein (beta-VLDL) (40 micrograms/ml) and 25-hydroxycholesterol (5
      micrograms/ml) prevented the increase in mRNA level for the LDL receptor, and HMG
      CoA reductase and the levels were 10-26% of the control at 8 h. The effect with
      beta-VLDL was sustained for 24 h. With 25-hydroxycholesterol, both LDL receptor
      and HMG-CoA reductase mRNA returned to base line by 24 h. In contrast, beta-VLDL
      increased cholesterol 7 alpha-hydroxylase mRNA level above the serum-free control
      within 8 h (+32%), and this was sustained for 24 h (+47%). There was a slight
      induction of cholesterol 7 alpha-hydroxylase mRNA levels by 25-hydroxycholesterol
      at 8 h (+18%); but by 24 h, its level was below that of the control (-47%). There
      was no induction of cholesterol 7 alpha-hydroxylase mRNA levels by beta-VLDL or
      25-hydroxycholesterol when the cells were grown in complete medium. As determined
      by nuclear run-on assay, the increase in the transcriptional rate of the
      cholesterol 7 alpha-hydroxylase gene in cells grown in serum-free medium (3.9
      fold of the rate in complete medium) and incubated with beta-VLDL (+68% above
      serum-free control) at 8 h, was comparable with the increase in mRNA levels (3.5
      fold and +32%, respectively). When bile salts were added to serum-free medium and
      cells cultured for up to 24 h, chenodeoxycholate and glycochenodeoxycholate
      caused a marked suppression of the level of cholesterol 7 alpha-hydroxylase mRNA,
      while cholate and its conjugates did not.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8144507
TI  - Biochemical characterization of the developmental stage- and tissue-specific
      erythroid transcription factor, NF-E4.
AB  - Analysis of the nuclear factors responsible for erythroid gene regulation has led
      to the cloning of several transcriptional regulatory proteins with clear lines of
      evidence suggesting or demonstrating their roles in tissue-specific gene
      expression. However, the erythroid cell lineage-restricted proteins that have
      been characterized to date do not differ significantly in activity during the
      distinct developmental stages of erythropoiesis, a characteristic that might be
      expected for a nuclear factor that actively participates in the differential
      regulation of various alpha- or beta-type globin genes (called globin gene
      switching) at distinct stages of embryonic development. We reported previously
      the identification of such a differentially expressed DNA binding activity, which
      appeared to be present in mature definitive (adult) erythroid cells but absent in
      immature definitive or primitive (embryonic) erythroid cells. Here we detail the
      biochemical properties of this erythroid tissue- and developmental stage-specific
      DNA binding activity (called nuclear factor-erythroid 4; NF-E4), which contains
      characteristics of a molecule that may be intimately involved in globin gene
      switching.

PMID- 8144508
TI  - A mixture of Manduca sexta aminopeptidase and phosphatase enhances Bacillus
      thuringiensis insecticidal CryIA(c) toxin binding and 86Rb(+)-K+ efflux in vitro.
AB  - CryIA(c) delta-endotoxin, a member of the CryI family of Bacillus thuringiensis
      insecticidal proteins, specifically recognizes and binds with high affinity to
      target proteins in the midgut of susceptible insects. Protein blots of Manduca
      sexta brush-border membranes probed with 125I-CryIA(c) identify a major binding
      protein of 120 kDa and a minor binding protein of 65 kDa. Monoclonal antibodies
      were raised against the 120-kDa toxin binding protein. Using isoelectric focusing
      and monoclonal antibodies (2B3, 8G1, and 12B8) 120- and 65-kDa brush-border
      proteins were isolated. Labeled CryIA(c) and monoclonal antibodies probed to
      blots of the affinity-selected proteins recognized the 120- and 65-kDa proteins.
      When reconstituted into phospholipid vesicles, antibody-selected proteins
      increased toxin binding (35%) and enhanced toxin-induced 86Rb+ release up to 1000
      fold. The 120-kDa protein was identified as aminopeptidase N (EC 3.4.11.2). A
      CryIA(c)-sensitive phosphatase was also present in the 120/65-kDa protein
      mixture. These findings provide the first identification of B. thuringiensis
      toxin binding proteins, although confirmation is needed in vivo.

PMID- 8144509
TI  - The shape of high molecular weight kininogen. Organization into structural
      domains, changes with activation, and interactions with prekallikrein, as
      determined by electron microscopy.
AB  - Knowledge of the organization of the kininogen gene and protein structure and
      function correlations has allowed the development of a model of high molecular
      weight kininogen. Domains 1-3 on the heavy chain are evolutionarily related to
      cystatin and the latter two are inhibitors of cysteine proteases. Proteolytic
      cleavage in domain 4 to release bradykinin causes a conformational change,
      exposing a surface-binding region (domain 5) on the disulfide-linked light chain.
      The carboxyl-terminal domain 6 contains a zymogen binding sequence for factor XI
      and prekallikrein which, with domain 5, accounts for its cofactor activity. To
      explore further the domain structure, we have determined the shapes of high
      molecular weight kininogen and prekallikrein by electron microscopy of rotary
      shadowed preparations and computer image processing. High molecular weight
      kininogen appears to be a linear array of three linked globular regions about 16
      nm long, with the two ends also connected by another thin strand. Both
      prekallikrein and kallikrein have a compact globular shape, with a subdivision
      that is sometimes visible. Different functional domains of high molecular weight
      kininogen were identified by monoclonal antibodies against these regions, as well
      as ligand binding of prekallikrein. These studies indicate that one end globular
      region is the prekallikrein-binding domain, the other comprises the cysteine
      protease inhibitor domains and the smaller central nodule is the surface-binding
      domain. Cleavage of high molecular weight kininogen with plasma kallikrein to
      yield two-chain high molecular weight kininogen results in a striking change in
      conformation: the central surface-binding domain swings out so that it is still
      adjacent to the prekallikrein-binding domain but no longer in the middle. These
      structural studies provide insight into the interactions of these proteins and
      aspects of the mechanisms of their actions.

PMID- 8144510
TI  - Similarity of three-dimensional microcrystals of detergent-solubilized (Na+,K+)
      ATPase from pig kidney and Ca(2+)-ATPase from skeletal muscle sarcoplasmic
      reticulum.
AB  - Image analysis has been used to compare the projection structure of three
      dimensional crystals of (Na+,K+)-ATPase from pig kidney and the Ca(2+)-ATPase
      from rabbit muscle sarcoplasmic reticulum. These crystals, formed from detergent
      solubilized protein in the presence of 20% glycerol and at a low detergent to
      protein ratio, crystallize in nearly identical unit cells in the space group C2.
      Average cell dimensions for the Ca(2+)-ATPase were a = 166.8 +/- 4.5 A, b = 57.7
      +/- 4.4 A, gamma = 90 degrees while those for the (Na+,K+)-ATPase were a = 166.2
      +/- 3.8A, b = 54.25 +/- 3.5A, gamma = 90 degrees. Their projected structures at
      the resolution of 25-A resolution are indistinguishable. Thus, the (Na+,K+)
      ATPase crystals appear to contain only the alpha chain of the alpha beta
      heterodimer found in native membranes. We conclude from this that the three
      dimensional structure of the alpha chain of the (Na+,K+)-ATPase is very similar
      to that of the Ca(2+)-ATPase despite their relatively weak overall sequence
      homology.

PMID- 8144511
TI  - Constitutive endothelin-1 overexpression promotes smooth muscle cell
      proliferation via an external autocrine loop.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide originally purified from
      endothelial cell-conditioned medium. It has multiple biological activities and
      has been implicated in a number of human diseases, including hypertension and
      atherosclerosis. Contradictory reports have been published regarding whether ET-1
      is a mitogen for vascular smooth muscle cells (SMC); thus, this issue is
      presently unresolved. In this study, we demonstrate that rat aortic SMC express
      functional endothelin cell surface receptors but do not proliferate when ET-1 is
      added to serum-free culture medium on every other day for a period of 1 week. To
      determine whether ET-1 could function in an autocrine manner to promote SMC
      growth, we transfected this same cell line with an ET-1 expression plasmid.
      Several independent lines expressing variable levels of ET-1 mRNA and
      biologically active ET-1 were obtained. Cell proliferation assays indicated that
      the transfected SMC line secreting the highest level of ET-1 had an enhanced
      growth rate when compared with untransfected or vector-alone transfected cells.
      The growth rate of this SMC line, but not of untransfected cells, was
      significantly reduced when the ETA receptor subtype-selective antagonist BQ-123
      was included in the culture medium. These results indicate that constitutive ET-1
      overexpression can promote SMC proliferation. Therefore, it is possible that
      under certain conditions ET-1 could be an important factor controlling SMC
      replication in vivo.

PMID- 8144512
TI  - Molecular cloning of brevican, a novel brain proteoglycan of the
      aggrecan/versican family.
AB  - To clone novel brain proteoglycans, we employed a strategy based on polyclonal
      antisera that recognize multiple proteoglycan core proteins. By using an
      antiserum raised against a fraction enriched for proteoglycans, we isolated three
      groups of cDNAs from a bovine brain lambda gt11 library. One of the cDNA groups
      has been fully sequenced and shown to encode a novel proteoglycan core protein of
      the aggrecan/versican family. This proteoglycan, named brevican, carries
      chondroitin sulfate chains, and, like other members of the family, contains a
      hyaluronic acid-binding domain in its N-terminal region, an epidermal growth
      factor-like repeat, a lectin-like and a complement regulatory protein-like
      domains in its C-terminal region. In contrast, the central region of brevican is
      much shorter than that of aggrecan, versican, or neurocan, and shows little
      homology with these proteoglycans. Brevican core protein exists as a 145 kDa full
      length form and a 80 kDa N terminally truncated form. A significant amount of
      brevican devoid of any glycosaminoglycan chains is present in the brain,
      indicating that brevican is a "part-time" proteoglycan. Northern blot analysis
      reveals that a single 3.3-kilobase brevican transcript is present predominantly
      in the brain, and that it is expressed in primary cerebellar astrocytes but not
      in neurons.

PMID- 8144513
TI  - A role for Raf-1 in the divergent signaling pathways mediating insulin-stimulated
      glucose transport.
AB  - Downstream mediators of insulin signaling are thought to include multiple
      cytoplasmic serine/threonine kinases such as the product of the cellular proto
      oncogene c-raf-1. To investigate a role for the Raf-1 protein kinase in insulin
      stimulated glucose transport, a gene encoding an oncogenically activated Raf-1
      mutant was introduced into 3T3-L1 fibroblasts by retroviral gene transfer.
      Expression of activated Raf-1 in differentiated 3T3-L1 adipocytes markedly
      increases hexose uptake compared to control adipocytes or those infected with the
      retroviral vector. Basal 2-deoxyglucose uptake in adipocytes expressing activated
      Raf-1 is approximately 40-fold higher than in parental adipocytes, and insulin
      further increases uptake about 1.2-fold. As determined by the plasma membrane
      "sheet" assay, Raf-1-expressing adipocytes contain greatly elevated levels of the
      ubiquitous glucose transporter (GLUT1) on the cell surface in the absence or
      presence of insulin. Total cellular GLUT1 protein is increased about 5-fold. In
      contrast, activated Raf-1 affects neither the expression of the "insulin
      responsive" glucose transporter (GLUT4) nor its cellular distribution; GLUT4 is
      virtually undetectable on the plasma membrane in the absence of insulin and
      translocates normally following the addition of hormone. These data suggest that
      activation of Raf-1 mediates the chronic effect of insulin on hexose uptake but
      is not sufficient for the rapid translocation of GLUT4. Moreover, the
      differential effects of activated Raf-1 expression on the two transporter
      isoforms define divergent signaling pathways by which insulin regulates glucose
      transport in cultured adipocytes.

PMID- 8144514
TI  - An acrosomal protein, sp32, in mammalian sperm is a binding protein specific for
      two proacrosins and an acrosin intermediate.
AB  - An acrosomal protein, sp32, was completely purified from acid extracts of
      ejaculated porcine sperm. Purified sp32 gave a single 32-kDa protein band on SDS
      polyacrylamide gel electrophoresis and was characterized as a binding protein
      specific for 55-, 53-, and 49-kDa forms of (pro)acrosin. This protein was not
      capable of binding a 43-kDa acrosin intermediate and 35-kDa mature acrosin. sp32
      significantly accelerated autoactivation of proacrosin at a basic pH in vitro and
      affected the maturation pathway of proacrosin. In the presence of sp32, the 49
      kDa acrosin intermediate from the 55- and 53-kDa proacrosins was accumulated,
      instead of the 43-kDa acrosin intermediate. These results suggest that sp32
      interacts with both the amino- and carboxyl-terminal sequences of the 53-kDa
      proacrosin. The cDNA clones coding for porcine and guinea pig sp32 have been
      identified from testis cDNA libraries in lambda gt11. The deduced amino acid
      sequence indicates that sp32 is initially synthesized as a 61-kDa precursor
      protein with a putative signal peptide at the amino terminus. The carboxyl
      terminal half of the precursor molecule corresponds to the mature sp32. Thus,
      sp32 is produced by post-translational modification of the precursor. The binding
      of sp32 to proacrosin may be involved in packaging the acrosin zymogen into the
      acrosomal matrix.

PMID- 8144515
TI  - Detection of changes in near-membrane Ca2+ concentration using a novel membrane
      associated Ca2+ indicator.
AB  - A Ca2+ indicator has been synthesized and characterized which can be used to
      monitor rapid changes in the free Ca2+ concentration ([Ca2+]) immediately
      adjacent to cell membranes. This indicator, referred to as C18-Fura-2, consists
      of a Fura-2 molecule conjugated to a lipophilic alkyl chain which will insert
      into cell membranes. When associated with cell membranes in low concentrations,
      C18-Fura-2 exhibits an excitation spectrum with a large Stokes shift and a single
      isobestic point, thus [Ca2+] can be calculated ratiometrically. The apparent Ca2+
      dissociation constant of cell-associated C18-Fura-2 is around 150 nM. C18-Fura-2
      orients in the cell membrane so that the fluorophore is facing the side to which
      it was applied. C18-Fura-2 was used to record rapid changes in intracellular
      [Ca2+] which occurred in response to membrane depolarization in isolated smooth
      muscle cells. The initial rise of the [Ca2+] transient reported by C18-Fura-2 was
      four to six times faster than the rise of the [Ca2+] transient reported by
      cytosolic Fura-2. This result suggests that C18-Fura-2 was located at the plasma
      membrane near sites of Ca2+ influx and indicates that membrane-associated Ca2+
      indicators can be used to detect rapid, localized changes in [Ca2+] which are
      obscured in signals recorded using water-soluble, bulk cytosolic fluorescent Ca2+
      indicators.

PMID- 8144516
TI  - Two related proteolipids and dolichol-linked oligosaccharides accumulate in motor
      neuron degeneration mice (mnd/mnd), a model for neuronal ceroid lipofuscinosis.
AB  - In this study, we show that two biochemical markers of neuronal ceroid
      lipofuscinoses (NCLs) are present in a mutant mouse (mnd/mnd) that exhibits
      symptoms of the disease. Subunit c of the mitochondrial F1F0-ATP synthase, a
      proteolipid that accumulates in storage bodies of most forms of NCL and several
      animal models, is dramatically increased in mnd/mnd mouse brain, kidney, liver,
      heart, and pancreas. Interestingly, another related proteolipid, subunit c of the
      vacuolar H(+)-ATPase, also accumulates in several mnd/mnd tissues. The molar
      ratio of the vacuolar subunit c to the F1F0 subunit c is approximately one to two
      in enriched storage bodies from brain. The relative accumulation of the vacuolar
      subunit c correlates with its abundance in normal tissues. It appears in
      decreasing amounts in brain, kidney, and liver and is not detected in heart or
      pancreas. Aged mice and two mutant mouse lines, juvenile bare (jb) and
      mucopolysaccharidosis, type VII (gusmps), did not accumulate either of these
      proteolipids. Dolichol-linked oligosaccharides also accumulate in NCLs and are
      increased 17-fold in mnd/mnd mouse brain. Thus, mnd/mnd mice seem to be an
      excellent model for NCLs since they not only share clinical signs and
      histopathology, but also two biochemical markers. The accumulation of the
      vacuolar subunit c in this model may prove to be a marker for distinguishing
      different forms of NCLs.

PMID- 8144517
TI  - Matrix effects suggest an important influence of DNA-polyacrylamide interactions
      on the electrophoretic mobility of DNA.
AB  - The electrophoretic mobilities of 34 DNA fragments with a varied phasing of two A
      tract bends have been determined in different polyacrylamide gels. They are
      perfectly described by a cosine function. A systematic variation of the
      polyacrylamide gel matrix revealed that not only the absolute electrophoretic
      mobilities of these distance variants, but also their amplitudes and the
      positions of their extrema, depend on the polyacrylamide content. The
      displacement of the extrema with increasing polyacrylamide content is attributed
      to gel-induced unwinding of the DNA. None of these matrix effects can be
      explained by the change of the pore sizes, which is generally regarded as the
      central parameter determining electrophoretic mobility of DNA in gels. Instead,
      we hypothesize an interaction between the electrophoresed DNA and the
      polyacrylamide matrix and discuss a new qualitative model for electrophoresis of
      DNA in polyacrylamide gels which accounts for these observations.

PMID- 8144518
TI  - DNA strand exchange in the absence of homologous pairing.
AB  - The strand exchange reaction that is widely used for in vitro studies on
      recombination of DNA molecules is generally presumed to result from a preceding
      homologous pairing step. With the use of a single-stranded circular DNA and a
      short homologous linear duplex fragment as substrates in a model strand exchange
      reaction, it was found that modest concentrations of polyethylene glycol or salt
      promote formation of heteroduplex molecules and strand exchange. When the duplex
      fragment was partially resected with an exonuclease exposing a short single
      stranded stretch on the ends, the reaction was promoted by the addition of
      commercial bovine serum albumin. The transcription factor TFIIIA promoted strand
      exchange when the DNA substrates contained the cognate DNA binding sequence
      recognized by the protein. These observations suggest that detection of strand
      exchange in vitro does not necessarily imply a preceding homologous pairing step.

PMID- 8144519
TI  - Chromatin decondensation in Drosophila embryo extracts.
AB  - Decondensation of sperm chromatin in cell-free Drosophila embryo extracts was
      efficient, rapid, and synchronous. The decondensation activity was N
      ethylmaleimide-resistant, soluble, and heat-stable. Two specific proteins, X and
      Y, were removed selectively from Xenopus sperm coincident with morphological
      decondensation. A heat-stable protein, p22, was purified to apparent homogeneity
      from Drosophila melanogaster embryos by a procedure optimized for the
      purification of Xenopus laevis nucleoplasmin. Although itself capable of
      catalyzing decondensation of Xenopus sperm, the precise relationship of
      Drosophila p22 to Xenopus nucleoplasmin is unclear. Drosophila p22 and Xenopus
      nucleoplasmin were immunologically distinct. Moreover, p22 was present as a
      nuclear protein throughout Drosophila development as determined both by
      immunoblot and by indirect immunofluorescence analyses. Drosophila embryo
      extracts largely or completely immunodepleted of p22 lost some but not all heat
      stable decondensation activity. These observations lead to the conclusion that
      Drosophila embryo extracts contain at least two heat-stable sperm decondensation
      factors.

PMID- 8144520
TI  - Isolation and characterization of a platelet-derived macrophage-binding
      proteoglycan.
AB  - A macromolecule in human platelet secretory products was demonstrated previously
      to inhibit the binding and uptake of acetoacetylated (AcAc) low density
      lipoproteins (LDL) by scavenger receptors on mouse peritoneal macrophages. In the
      current study, this macromolecule was purified to apparent homogeneity by DEAE
      Sephacel chromatography, Sephacryl S-300 chromatography, and sucrose gradient
      centrifugation. SDS-polyacrylamide gel electrophoresis revealed a single band
      with an apparent molecular mass of approximately 120 kDa. Chemical analysis
      indicated that the macromolecule (designated platelet-derived macrophage-binding
      proteoglycan (PDMBP)) was a chondroitin 4-sulfate proteoglycan with an
      approximately 32-kDa core protein. A polyclonal antibody produced against this
      proteoglycan identified only PDMBP on Western blots of platelet secretory
      products and removed all ability of these products to inhibit the binding of AcAc
      LDL to macrophages. Treatment of purified PDMBP with protease or chondroitinase
      AC or ABC abolished the ability of the proteoglycan to inhibit the binding of
      AcAc LDL to macrophages. Binding studies using radiolabeled PDMBP demonstrated
      that the proteoglycan bound directly to the macrophage cell surface and was
      competitively inhibited by AcAc LDL, acetyl-LDL, fucoidin, and unlabeled PDMBP.
      PDMBP inhibited binding of 125I-labeled AcAc LDL to macrophages but had no effect
      on binding to endothelial cells. The finding that PDMBP binds to the scavenger
      receptor on macrophages suggests a mechanism for the inhibition of foam cell
      formation and suggests that the receptor could be involved in the plasma
      clearance of chondroitin sulfate proteoglycans.

PMID- 8144521
TI  - Glutathione-ascorbic acid antioxidant system in animals.

PMID- 8144522
TI  - A family of mitogen-activated protein kinase-related proteins interacts in vivo
      with activator protein-1 transcription factor.
AB  - The activator protein-1 (AP-1) transcription factor modulates expression of genes
      involved in growth regulation, differentiation, and neoplastic transformation.
      Several mitogen-activated protein kinases (MAP kinases) as well as other kinases
      phosphorylate c-Jun and c-Fos in vitro and are postulated to control AP-1
      activity. However, since many protein kinases phosphorylate substrates in vitro
      with which they have no association in vivo, we sought evidence for interaction
      in vivo between AP-1 and MAP kinase proteins. We now report detection of an
      association in vivo of MAP kinase-related proteins with c-Jun and AP-1 dimers by
      peptide mapping and two-dimensional electrophoretic analyses of proteins co
      immunoprecipitated with AP-1 antigens. Extracellular signal-regulated kinase-2
      and several apparently novel MAP kinase-related proteins are among the species
      that bind to AP-1. The large number of MAP kinase-related proteins associated
      with AP-1 implicates them on an important gene regulation pathway. Combinatorial
      association between MAP kinase-related proteins and AP-1 dimers could potentially
      create numerous distinct complexes that could regulate diverse genes.

PMID- 8144523
TI  - An amino-terminal fragment of apolipoprotein B binds to lipoprotein lipase and
      may facilitate its binding to endothelial cells.
AB  - Lipoprotein lipase (LPL), the principal enzyme which hydrolyzes triglycerides in
      circulating plasma lipoproteins, functions while bound to the luminal surface of
      endothelial cells. LPL is a heparin-binding protein and has been assumed to
      associate with endothelial cell heparan sulfate proteoglycans (HSPG). Recently,
      using ligand blotting and affinity chromatography we identified a 116-kDa heparin
      releasable LPL-binding protein (hrp-116) from endothelial cells which was not a
      HSPG (Sivaram, P., Klein, M. G., and Goldberg, I. J. (1992) J. Biol. Chem. 267,
      16517-16522). This suggested that, like a number of other heparin-binding
      proteins, LPL binding to cells also involves non-HSPG proteins. Using heparin
      agarose affinity chromatography, a 116-kDa LPL-binding protein was purified from
      endothelial cell extracts. Microsequencing of peptides generated by Lys-C
      protease digestion revealed complete homology with four different regions in the
      NH2-terminal part of human apolipoprotein B (apoB). Western blots using anti-apoB
      monoclonal antibodies (mAb) that recognize the NH2-terminal region of apoB
      confirmed that a 116-kDa fragment of apoB was present on endothelial cell
      membranes. Further evidence that LPL associates with the NH2-terminal region of
      apoB was obtained by showing 1) that an NH2-terminal fragment of apoB obtained
      from apoB-transfected CHO cells bound LPL on ligand blots and 2) that NH2
      terminal fragments of apoB generated by thrombin digestion of low density
      lipoprotein bind LPL. Evidence that the NH2-terminal region of apoB mediates LPL
      interaction with endothelial cells was obtained using monoclonal antibodies. mAb3
      and mAb19, which recognize epitopes near the NH2 terminus of apoB, inhibited 125I
      LPL binding to cells by 60-65%. In contrast, mAb47, which has determinants at the
      COOH-terminal end of apoB, inhibited LPL binding by only about 10%. The
      inhibitory effects of mAb3 and mAb19 were abolished following treatment of cells
      with heparin, which removes the 116-kDa LPL-binding protein. Furthermore,
      incubation of 125I-LPL in medium containing an NH2-terminal apoB fragment reduced
      LPL binding to cells. These data suggest that an NH2-terminal fragment of apoB
      that binds to endothelial surfaces facilitates LPL binding to cells.

PMID- 8144524
TI  - Human mast cell tryptase activates single-chain urinary-type plasminogen
      activator (pro-urokinase).
AB  - Human lung mast cell tryptase is a trypsin-like serine proteinase that is stored
      in mast cell granules and released by activated mast cells. Here we report that
      mast cell tryptase is a potent activator of single-chain urinary-type plasminogen
      activator (scu-PA, or prourokinase), the zymogen form of urinary-type plasminogen
      activator (u-PA). Activation was complete within 75 min using an enzyme:substrate
      molar ratio of 1:50 and was accompanied by cleavage of scu-PA at Lys158-Ile159,
      generating active two-chain u-PA. The reaction was dependent on enzyme
      concentration and obeyed Michaelis-Menten kinetics. Kinetic constants calculated
      for scu-PA activation by mast cell tryptase are Km = 34 microM, Vmax = 3.6 pmol
      of u-PA/min, and kcat = 0.08 s-1. These data suggest that tryptase from tumor
      associated mast cells may participate in the activation of scu-PA.

PMID- 8144525
TI  - Expression of NAD glycohydrolase activity by rat mammary adenocarcinoma cells
      transformed with rat T cell alloantigen RT6.2.
AB  - RT6.2 is a 26-kDa alloantigen expressed only on post-thymic T cells and attached
      to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. It has
      been reported that expression of RT6.2 in animal models may correlate with
      lymphopenia and genetically-induced insulin-dependent diabetes mellitus. Its
      physiological function is unclear. Since RT6.2 has significant amino acid
      identity with a GPI-anchored rabbit muscle NAD:arginine ADP-ribosyltransferase,
      RT6.2 was expressed in rat mammary adenocarcinoma cells and the ability of the
      expressed protein to catalyze ADP-ribose transfer reactions was examined. Cells
      transformed with the RT6.2 gene expressed NAD glycohydrolase activity that was
      released from intact cells by phosphatidylinositol-specific phospholipase C,
      consistent with its presence on the cell surface. A similar activity was not
      detected with vector-transformed cells. RT6.2 did not ADP-ribosylate simple
      guanidino compounds. The molecular weight of the phosphatidylinositol-specific
      phospholipase C-released NAD glycohydrolase, determined by SDS-polyacrylamide gel
      electrophoresis, was 22,000-24,000, in good agreement with that of native RT6.2.
      These results strongly suggest that the rat T cell alloantigen RT6.2 is a GPI
      anchored NAD glycohydrolase.

PMID- 8144526
TI  - Primary structural constraints of P-loop of mitochondrial F1-ATPase from yeast.
AB  - Nucleotide binding proteins, including ras, elongation factor Tu, adenylate
      kinase, and the mitochondrial F1-ATPase have a glycine-rich motif known as the P
      loop or the Walker A sequence (Walker, J. E., Saraste, M., Runswick, M. J., and
      Gay, N. J. (1982) EMBO J. 1, 945-951). The primary structural constraints have
      been determined in the P-loop located in the beta-subunit of the mitochondrial
      ATPase from yeast. The primary structural constraints were determined for 9
      residues that form the P-loop, 190Gly-Gly-Ala-Gly-Val-Gly-Lys-Thr-Val198. Each
      residue was tested individually for possible functional replacements while
      keeping the primary structure of the remainder of the molecule constant. This
      analysis indicates with greater than 95% confidence that Gly190,Gly195, and
      Lys196 are invariant and Thr197 can only be replaced with Ser. The most alterable
      residue is Gly191, where 10 replacements, even Phe, form a functional enzyme. The
      remaining positions allow some amino acid replacements while restricting others.
      The primary structural constraints of the P-loop of the mitochondrial F1 suggests
      that the three-dimensional structure of the P-loop is similar to that of ras.

PMID- 8144527
TI  - Interaction of a legume lectin with two components of the bacterial cell wall. A
      crystallographic study.
AB  - We describe herein the refined high resolution x-ray structures of two components
      of the bacterial cell wall, muramic acid and muramyl dipeptide complexed to
      isolectin I from Lathyrus ochrus seeds. In both complexes, only the ring hydroxyl
      oxygen atoms of the bound sugar establish direct hydrogen bonds with isolectin I,
      as in the case of all the previously determined monosaccharide-lectin complexes.
      In addition, the lactyl methyl of both components strongly interacts via
      hydrophobic contacts with the side chains of residues Tyr100 and Trp128 of
      isolectin I, which could explain the higher affinity of isolectin I for muramic
      acid as compared with glucose. These 2 residues, however, are not involved in the
      stabilization of the oligosaccharide-isolectin I complexes. The dipeptide (D-Ala
      D-iGln) of the second component is in stacking interaction with the N-acetyl
      group of glucose and with loop Gly97-Gly98 of isolectin I. In addition to these
      van der Waals' contacts, the dipeptide interacts with the lectin via well ordered
      water molecules also. Superposition of the structures of the muramyl dipeptide
      complex and of the muramic acid complex shows that the glucose ring in the
      dipeptide compound is tilted by about 15 degrees in comparison with that of
      muramic acid. The fact that the lactyl group has the same confrontation in both
      components reveals that the lectin is stereospecific and recognizes only
      diastereoisomer S of this group, which better fits the saccharide-binding site.

PMID- 8144528
TI  - Isolation and characterization of cDNA clones for chloroplast translational
      initiation factor-3 from Euglena gracilis.
AB  - A complete cDNA clone encoding Euglena gracilis chloroplast translational
      initiation factor 3 (IF-3chl) has been obtained. Analysis of the sequence
      indicates that the IF-3chl mRNA contains the spliced leader found at the 5' end
      of nuclear encoded mRNAs in E. gracilis. The open reading frame for IF-3chl
      encodes a 537-amino acid protein. IF-3chl appears to be divided into four
      domains. The first 140 amino acids correspond to a transit peptide required for
      the import of IF-3chl into the chloroplast. The mature form of IF-3chl
      encompasses domains 2-4 and is about twice the size of Escherichia coli IF-3. The
      second domain has no homology to other known proteins. It begins with a stretch
      of 35 residues, of which about 30% are proline. Downstream from this region is a
      stretch of about 25 amino acids with a repeating (GX)n motif followed by a very
      acidic region. The third domain comprises a region of about 175 residues and has
      between 31 and 37% homology to the IF-3s found in other organisms. The IF-3
      homology domain is followed by an acidic region which has no detectable homology
      to other sequences. Analysis of E. gracilis genomic DNA suggests that there are
      about four copies of the IF-3chl gene, one of which is probably a pseudogene. The
      activity of IF-3chl is inducible by light. However, the IF-3chl mRNA is present
      in approximately equal amounts in both dark- and light-grown cells, suggesting
      that the light-dependent induction of IF-3chl activity is post-transcriptional.

PMID- 8144529
TI  - Factor IXa protects factor VIIIa from activated protein C. Factor IXa inhibits
      activated protein C-catalyzed cleavage of factor VIIIa at Arg562.
AB  - Factor VIIIa is inactivated by both factor IXa and activated protein C. The
      latter protease rapidly attacked a site at Arg562 (A2 subunit), whereas both
      proteases slowly cleaved factor VIIIa at Arg336 (A1 subunit). Cofactor
      inactivation catalyzed by activated protein C was 8-fold faster than that
      catalyzed by factor IXa. Simultaneous reaction of factor VIIIa with the two
      enzymes resulted in a rate of inactivation intermediate to that observed for the
      individual proteases. Under these conditions, the activated protein C-catalyzed
      cleavage at Arg562 was inhibited such that cofactor inactivation resulted
      primarily from cleavage at Arg336. Substitution of factor IXa modified in its
      active site with 6-(dimethylamino)-2-naphthalenesulfonyl-glutamylglycylarginyl++
      + chloromethyl ketone (DEGR-IXa) for the native enzyme yielded a similar rate of
      activated protein C-catalyzed cleavage at the A1 site, whereas cleavage at the A2
      site was virtually eliminated. However, the inclusion of protein S resulted in a
      marked increase in cleavage at the A2 site that correlated with an increased rate
      of cofactor inactivation. Active site-modified activated protein C inhibited the
      factor IXa-dependent enhancement of factor VIIIa reconstitution from isolated
      subunits. In addition, the factor VIIIa-dependent fluorescence enhancement of
      DEGR-activated protein C was inhibited by EGR-IXa. These results indicate that
      factor IXa can reduce the rate of activated protein C-catalyzed cofactor
      inactivation by selectively blocking cleavage at the A2 domainal site, an effect
      reversed by protein S. One mechanism consistent with the reciprocal inhibitory
      effects of the proteases is that activated protein C and factor IXa occupy
      overlapping sites on the cofactor. Thus, factor IXa may protect factor VIIIa by
      preventing activated protein C binding.

PMID- 8144530
TI  - Operon of vacuolar-type Na(+)-ATPase of Enterococcus hirae.
AB  - The Gram-positive bacteria Enterococcus hirae expel sodium by two systems: a
      Na+/H(+)-antiporter and a vacuolar-type Na(+)-ATPase. We isolated a mutant,
      NalkA, defective in the Na(+)-ATPase. NalkA grew normally at neutral pH but was
      unable to grow in the presence of > 100 mM sodium at pH 9.5. By functional
      complementation at high pH, we cloned pES1, a plasmid from an E. hirae gene bank
      containing a 5.2-kilobase pair region of genomic DNA. The genomic DNA in pES1
      contains five complete open reading frames, ntpM, -N, -O, -P, and -Q, encoding
      proteins of 75, 16, 23, 38, and 11 kDa. A sixth incomplete open reading frame,
      ntp 'L, precedes ntpM. The 3'-end of the cloned DNA overlaps with a previously
      published sequence encoding the ntpA and ntpB subunits of the E. hirae Na(+)
      ATPase (Takase, K., Yamato, I., and Kakinuma, Y. 1993) J. Biol. Chem. 268, 11610
      11616). The insert of pES1 therefore represents the upstream region of the ntp
      operon that encodes the E. hirae Na(+)-ATPase. Complementation analysis with
      various deletions derived from pES1 suggest that the original mutation is in the
      ntpM gene. Of the new genes described here, three exhibited significant sequence
      similarity to known proteins; ntpM shares 24% identical amino acid residues with
      the "116-kDa" subunits of eukaryotic vacuolar ATPases, ntpN exhibits 28% sequence
      identity with the 16-kDa proteolipid of human vacuolar ATPase, and ntpO has
      sequence homology to the 31-kDa subunit of the bovine kidney vacuolar ATPase. No
      known proteins with sequence similarity to ntp'L, -P, or -Q could be identified.
      Disruption of either ntpM, -N, or -O in wild-type cells by cassette mutagenesis
      resulted in mutants unable to effect ATP-driven sodium extrusion. NtpM, -N, and 
      O therefore represent three new gene products involved in sodium extrusion by the
      vacuolar-type Na(+)-ATPase of E. hirae, and three more gene products, NtpL, -P,
      and -Q, may also be constituents of this enzyme. The ntp operon thus contains at
      least eight genes.

PMID- 8144531
TI  - The actin side-binding domain of gelsolin also caps actin filaments. Implications
      for actin filament severing.
AB  - Gelsolin is an actin filament-severing and -capping protein which is inhibited by
      polyphosphoinositides (PPI). Severing requires gelsolin binding to the side of
      the filaments through a site in segments 2 and 3 (S2-3) to position another site
      in segment 1 (S1) to sever filaments. In this paper, we report that S2-3, like
      S1, caps actin filaments. Since neither S1 and S2-3 caps as well as gelsolin, and
      neither severs actin filament, S2-3 may actively contribute to severing by
      capping filaments cooperatively with S1. We used deletional mutagenesis to locate
      the S2-3 sequence required for actin filament side binding, capping, and PPI
      binding and found that these sites are located close to the NH2 terminus of S2
      (residues 161-172). S3, a segment which has no known function up to now and does
      not by itself bind actin, contributes to stable capping and may contain an
      additional PPI-binding site.

PMID- 8144532
TI  - Incorporation of [32P]orthophosphate into inorganic polyphosphates by human
      granulocytes and other human cell types.
AB  - When human peripheral blood granulocytes were metabolically labeled at 37 degrees
      C with [32P]orthophosphate, inorganic polyphosphates became preferentially
      radiolabeled. Incorporation of radiolabel into the polymer appeared to be ATP
      independent. [32P]Polyphosphate was identified by its (i) characteristic lability
      to acid hydrolysis, (ii) insolubility in barium acetate (pH 4.5), (iii)
      conversion to [32P]trimetaphosphate, (iv) hydrolysis to [32P]orthophosphate by an
      exopolyphosphate (Saccharomyces cerevisiae scPPX1), and (v) conversion to a
      "phosphate ladder" which co-migrated on a polyacrylamide gel with a synthetic
      phosphate ladder. Also, indirect evidence suggested that the [32P]polyphosphate
      was strongly, noncovalently associated with another unknown molecule. Particulate
      fractions (13,000 x g) from lysates of human granulocytes, skin fibroblasts, HL
      60 and SK-N-SH cells, all demonstrated radiolabeling of polyphosphate when
      incubated at 37 degrees C with [32P]orthophosphate.

PMID- 8144533
TI  - Characterization of two different forms of mitogen-activated protein kinase
      kinase induced in polymorphonuclear leukocytes following stimulation by N
      formylmethionyl-leucyl-phenylalanine or granulocyte-macrophage colony-stimulating
      factor.
AB  - Incubation of polymorphonuclear leukocytes with chemoattractants, granulocyte
      macrophage colony-stimulating factor (GM-CSF), or phorbol 12-myristate 13-acetate
      (PMA) activated both mitogen-activated protein kinase kinase (MAPKK) and mitogen
      activated protein kinase (MAPK). Activation by chemoattractants was rapid and
      transient, being maximal by 1 min and decreasing by 10 min. The order of efficacy
      was formyl-met-leu-phe > C5a > > LTB4 > interleukin 8 > platelet-activating
      factor. In contrast, activation by GM-CSF or PMA was slow and sustained being
      maximal at 5 min and with little decrease by 30 min. Sustained MAPK activation
      required continuous activation of the MAPKK. The MAPKK induced by N
      formylmethionyl-leucyl-phenylalanine, GM-CSF, or PMA was resolved into two forms
      by anion exchange chromatography (Mono Q). Both corresponded to a 45-kDa MAPKK
      antigen by Western blotting and were inactivated by serine/threonine protein
      phosphatase 2A. Rechromatography of both forms after dephosphorylation resulted
      in the antigen's eluting slightly earlier on the Mono Q gradient than when in the
      active state. However, the two peaks remained separate, suggesting that they are
      not merely different phosphoforms of the same enzyme. The MAPK cascade is a
      signaling pathway common to many polymorphonuclear leukocyte stimulants, which
      may be activated transiently or in a sustained manner.

PMID- 8144534
TI  - ATP-dependent chaperoning activity of reticulocyte lysate.
AB  - We have developed an assay for chaperone-mediated protein renaturation using
      thermally denatured Firefly luciferase. Dilution of denatured luciferase (> 99%
      loss of activity) into reticulocyte lysate typically results in recovery of 5-15%
      activity. Addition of an ATP-regenerating system increases yields to > 60%, while
      heat shock or the addition of denatured proteins inhibits the chaperoning
      activity. Reticulocyte lysate contains abundant quantities of the heat shock
      proteins, hsp90 and hsp70, and a 60-kDa protein homologous to the yeast stress
      protein, STI1. Immune isolated samples of these three proteins support recovery
      of up to 35% of luciferase activity in an ATP-dependent manner, suggesting that
      these or associated proteins are involved in the renaturation of luciferase.
      Furthermore, we observed a correlation between luciferase renaturation activity
      and the levels of hsp70 and hsp90 in reticulocyte lysate preparations. Purified
      hsp90 and hsp70, along with an ATP-regenerating system, are able to renature
      luciferase to greater than 20% of its original activity. This renaturation is
      most efficient when hsp90 and hsp70 are at about a 2:1 ratio and at
      concentrations similar to those found in reticulocyte lysate. This study provides
      evidence for an ATP-dependent chaperoning activity in reticulocyte lysate that
      involves a cooperative action of hsp70 and hsp90.

PMID- 8144535
TI  - Nucleotide substitutions differentially affect direct repeat and palindromic
      thyroid hormone response elements.
AB  - Thyroid hormone receptors are transcription factors that bind to specific DNA
      sequences and regulate gene expression in a ligand-dependent manner. Thyroid
      hormone response elements can be composed of direct repeat or palindromic
      arrangements of half-sites. The traditional half-site has been considered to be
      the sequence 5'-AGGTCA, although we recently demonstrated that the optimal
      monomer-binding site is 2 base pairs larger, 5'-TAAGGTCA. It has generally been
      presumed that alterations in half-site sequence have commensurate effects on gene
      expression from direct repeat and palindromic response elements. However, in the
      present studies we demonstrate that palindromic elements are highly dependent on
      the presence of the two 5'-nucleotides (TA) for function, whereas this portion of
      the response element has minimal influence on hormone induction from direct
      repeat elements. Hormone induction correlates poorly with binding affinity for
      thyroid hormone receptor monomers, homodimers, or heterodimers with retinoid X
      receptors, either in the absence or presence of ligands. We speculate that the
      magnitude of hormone induction may reflect protein conformation differences
      induced by a combination of the presence of the appropriate 5'-nucleotides plus
      half-site orientation.

PMID- 8144536
TI  - Peroxisomal beta-oxidation of branched chain fatty acids in rat liver. Evidence
      that carnitine palmitoyltransferase I prevents transport of branched chain fatty
      acids into mitochondria.
AB  - Fatty acid beta-oxidation was investigated in highly purified mitochondrial and
      peroxisomal preparations from rat liver. Under isotonic conditions, pristanic and
      homophytanic acid beta-oxidation in purified peroxisomes was severalfold greater
      compared to the oxidation in purified mitochondria. Branched chain fatty acid
      beta-oxidation in purified mitochondria was very low, and the oxidation was not
      stimulated by exogenous L-carnitine or L-malate. In contrast, stearic acid beta
      oxidation by purified mitochondria depended upon exogenous L-carnitine, and the
      oxidation was stimulated by L-malate. Both mitochondrial and peroxisomal beta
      oxidation of branched chain fatty acids was strongly inhibited by fatty acid-free
      bovine serum albumin, whereas stearic acid oxidation was either unaffected or
      slightly inhibited by bovine serum albumin. The results presented clearly
      indicate that branched chain fatty acids are mainly degraded in peroxisomes in
      rat liver. Branched chain fatty acids were efficiently converted to coenzyme A
      thioesters by purified mitochondria, peroxisomes, and microsomes. Although
      pristanic and phytanic acids were rapidly converted to pristanoyl-CoA and
      phytanoyl-CoA, respectively, they were not converted to carnitine esters by
      mitochondrial outer membranes. The results indicate that acyl-CoA synthetase and
      carnitine acyltransferase located at the mitochondrial outer membranes regulate
      entry of branched chain fatty acids into mitochondria. Mitochondrial carnitine
      acyltransferase I appears to be highly specific for straight chain fatty acids
      and restricts entry of branched chain fatty acids into mitochondria. Thus,
      branched chain fatty acids which cannot be transported across the mitochondrial
      membranes via the carnitine acyltransferase system are directed to peroxisomes
      for beta-oxidation. The results reported indicate that phytanic acid, the fatty
      acid which can be initially degraded by alpha-oxidation due to the presence of a
      beta-methyl group in the molecule, cannot be transported across the mitochondrial
      membranes. The data presented strongly suggest that phytanic acid alpha-oxidation
      occurs in organelles other than mitochondria and possibly in peroxisomes.

PMID- 8144537
TI  - Vanadium activates or inhibits receptor and non-receptor protein tyrosine kinases
      in cell-free experiments, depending on its oxidation state. Possible role of
      endogenous vanadium in controlling cellular protein tyrosine kinase activity.
AB  - We have shown that vanadium mimics several insulin effects in rat adipocytes, via
      a staurosporine sensitive cytosolic protein tyrosine kinase (CytPTK; Shisheva,
      A., and Shechter, Y. (1993) J. Biol. Chem. 268, 6463). Here we demonstrate that
      vanadium effects on protein tyrosine kinases are preserved after cell
      disintegration. Vanadium inhibits or activates protein tyrosine kinases depending
      on its oxidation state and the tyrosine kinase studied. Vanadyl (4+) but not
      vanadate (5+) inhibits receptor tyrosine kinases such as the insulin receptor
      (IC50 value = 23 +/- 4 microM) and the insulin-like growth factor-I receptor
      (IC50 = 19 +/- 3 microM). Inhibition is non-competitive with respect to ATP,
      Mn2+, or substrate concentrations. Preincubation of adipocytes with vanadyl (0.4
      mM), and staurosporine (which arrests the cytosolic enzyme) substantially
      inhibited insulin-stimulated lipogenesis. Vanadyl is readily oxidized to vanadate
      by hydrogen peroxide. In contrast, CytPTKs were poorly inhibited by vanadyl, and
      vanadate stimulated several CytPTKs 2-6 fold. CytPTK derived from rat adipocytes,
      liver and brain were activated, and CytPTK from Nb2 lymphoma cells was not
      affected. CytPTK extracted from insulin-responsive tissues are more sensitive to
      vanadate activation (ED50 = 3 +/- 0.7 microM), whereas the brain enzyme is less
      sensitive (ED50 = 27 +/- 3 microM). Tungstate, molybdate, and phenylarsine oxide
      also stimulate CytPTK, suggesting that the vanadate effect is secondary to
      inhibiting protein phosphotyrosine phosphatases. This study supports a working
      hypothesis implicating the intracellular vanadyl pool in modulating CytPTK
      activity. Any physiological conditions converting vanadyl to vanadate (i.e. H2O2
      production) will activate CytPTK and consequently CytPTK-dependent bioeffects.

PMID- 8144538
TI  - Zinc destabilizes DNA Watson-Crick pairs at AGCT.
AB  - Zinc, a component of a large number of enzymes and an abundant and essential
      trace metal, alters the structure of AGCT sites in negatively supercoiled DNA.
      Related sequences show little or no effect. Cobalt and cadmium show reactivities
      similar to zinc. The conformational change in DNA was fine mapped with
      haloacetaldehydes using chemical cleavage or primer extension methods. Since a
      many fold excess of zinc to AGCT sites is required to saturate the reaction, we
      propose that the zinc-AGT complex is preferentially accessible to the
      haloacetaldehyde probes due to a conformational deformation. Hence, zinc is the
      smallest ligand (by approximately 500-fold) that causes a perturbation of a
      specific DNA sequence.

PMID- 8144539
TI  - Selection of antibody single-chain variable fragments with improved carbohydrate
      binding by phage display.
AB  - A single-chain variable fragment (Fv) version of a murine monoclonal antibody,
      Se155-4, specific for Salmonella serogroup B O-polysaccharide, was used as a
      model system for testing monovalent phage display as a route for enhancing the
      relatively low affinities that typify anti-carbohydrate antibodies. Random single
      chain Fv mutant libraries generated by chemical and error-prone polymerase chain
      reaction methods were panned against the serogroup B lipopolysaccharide. Panning
      of a randomly mutated heavy chain variable domain library indicated selection for
      improved serogroup B binders and yielded six mutants, five of which showed wild
      type activity by enzyme immunoassay. Two of these were apparently selected on the
      basis of better functional single-chain Fv yield in Escherichia coli. A heavy
      chain mutation (Ile77-->Thr) in one mutant, 3B1, appeared to have a particularly
      dramatic effect, resulting in yields of approximately 120 mg/liter of functional
      periplasmic product. The sixth mutant, 4B2, had complementarity determining
      region 1 (CDR1) and CDR2 mutations and demonstrated 10-fold improved binding, by
      enzyme immunoassay, relative to the wild type. Extensive analysis of antigen
      antibody interactions indicated that the improved binding properties of 4B2 were
      attributable to a higher association rate constant and interaction with an
      epitope that is larger than the trisaccharide recognized by the wild type. None
      of the mutations involved known trisaccharide contact residues; this was
      consistent with analysis of wild type and mutant single-chain Fvs by titration
      microcalorimetry. Examination of the structure indicated that two mutations in
      the heavy chain CDR2 provided improved surface complementarity between the
      protein and the extended epitope encompassing 2 additional hexose residues.
      However, introduction of only the CDR2 mutations into the wild type structure
      failed to confer the improved binding properties of 4B2, indicating an indirect
      effect by the more distant mutations. Panning of randomly mutated light chain
      variable domain and full-length single-chain Fv mutant libraries did not yield
      mutants with improved assembly or binding properties.

PMID- 8144540
TI  - The NH2-terminal fibrin-binding site of fibronectin is formed by interacting
      fourth and fifth finger domains. Studies with recombinant finger fragments
      expressed in Escherichia coli.
AB  - The NH2-terminal 29-kDa Fib-1 fragment consisting of the first five finger
      modules of fibronectin (F1-5) binds reversibly to fibrin and facilitates cross
      linking by Factor XIII. To narrow down the fibrin-binding site within this
      region, we have used recombinant technology to express a number of individual
      fingers, rF1, rF2, rF3, rF4, and rF5, and their pairs, rF1-2 rF2-3, and rF4-5, as
      fusion proteins in Escherichia coli. These recombinant fragments were separated
      from the carrier maltose-binding protein by digestion with human factor Xa or
      other proteases, and their structural integrity was confirmed by spectroscopic
      and calorimetric methods. The recombinant F1 and F4-5 exhibited fluorescence
      detected melting transitions of the same magnitude and with the same midpoint
      (Tm) as their natural analogues prepared from Fib-1 by proteolysis. Differential
      scanning calorimetry experiments further demonstrated that these fragments are
      properly folded and have compact structures identical to the natural ones.
      Isolated rF4 melts at a much lower temperature than rF5 or the bimodular fragment
      rF4-5, indicating the loss of a stabilizing interaction between fingers 4 and 5.
      Comparison of fluorescence spectra of individual rF4 and rF5 with that of rF4-5
      was also consistent with an interaction that affects the environment of Trp
      residue(s). rF2 also melts at a lower temperature than rF3 or rF2-3, suggesting a
      stabilizing interaction between the second and third fingers as well. When tested
      on fibrin-Sepharose, only the bimodular fragment rF4-5 was able to bind. All
      other fragments, including individual fingers 4 and 5, failed to bind. Thus,
      fibrin binding is not a common property of all fingers. The results indicate that
      a recognition site for fibrin is located within fingers 4 and 5. The interaction
      between these neighboring domains may play an important role in proper
      orientation of the residues forming this site.

PMID- 8144541
TI  - Methotrexate-resistant variants of human dihydrofolate reductase. Effects of
      Phe31 substitutions.
AB  - Substitution of glycine or alanine for phenylalanine 31 in human dihydrofolate
      reductase produces variants that are inhibited less by methotrexate (MTX) than
      the previously reported serine variant. The 100 times decrease in MTX affinity
      for the glycine variant is due to slower binding, and to inability of the initial
      complex to isomerize to a nondissociating conformer. A polar group at position 31
      is unnecessary for resistance, but residues larger than serine confer no
      resistance. The glycine variant best fulfills criteria for gene therapy: low Km
      for H2folate, high kcat, and good stability. Although kcat is unaltered by these
      mutations, the rate of hydride transfer is greatly decreased. Presteady-state
      measurements have enabled a complete catalytic scheme to be constructed for the
      glycine variant that predicts observed steady-state behavior. The crystal
      structures of inhibitor complexes of the serine, alanine, and glycine mutants and
      of the wild-type enzyme show that the mutations cause little perturbation of the
      protein backbone, of side chains of residues at the active site, or of the bound
      inhibitor. A molecule of bound water occupies the space vacated by the phenyl
      group.

PMID- 8144542
TI  - The prosequence of Rhizopus niveus aspartic proteinase-I supports correct folding
      and secretion of its mature part in Saccharomyces cerevisiae.
AB  - Extracellular Rhizopus niveus aspartic proteinase-I (RNAP-I) was secreted
      effectively by Saccharomyces cerevisiae when RNAP-I with its preprosequence was
      synthesized in this organism (Horiuchi, H., Ashikari, T., Amachi, T., Yoshizumi,
      H., Takagi, M., and Yano, K. (1990) Agric. Biol. Chem. 54, 1771-1779). Certain
      deletions (delta pro, delta 1, delta 2), and amino acid substitutions (M1) in the
      prosequence blocked secretion of RNAP-I, although the protease protection assay
      revealed that even delta pro could be translocated across the membrane of the
      endoplasmic reticulum. When delta pro or M1 was synthesized simultaneously with
      the wild-type preprosequence in S. cerevisiae, secretion of RNAP-I was recovered.
      Therefore, the physical linkage of the prosequence to the mature region is not a
      prerequisite for secretion of active RNAP-I. Purified RNAP-I with the prosequence
      once denatured in 6 M guanidine HCl could be renatured and activated to have its
      enzymatic activity by removing guanidine HCl in vitro, but RNAP-I without the
      prosequence could not. Furthermore, the wild-type prosequence helped the recovery
      of the activity of the denatured RNAP-I in trans, but the prosequences of M1 with
      which secretion of RNAP-I was not observed in vivo, did not. From these results
      we concluded that the prosequence of RNAP-I supports correct folding of RNAP-I in
      the endoplasmic reticulum lumen and its subsequent secretion in S. cerevisiae.
      The functional role of the prosequence of an aspartic proteinase was elucidated.

PMID- 8144543
TI  - Inhibition of histone phosphorylation by staurosporine leads to chromosome
      decondensation.
AB  - In mammalian cells, hyperphosphorylation of histone H1 and phosphorylation of
      histone H3 correlate well with the G2 phase to metaphase condensation of
      chromosomes, and these phosphorylations most probably have a role in initiating
      and controlling the entry into mitosis. The protein kinase inhibitor
      staurosporine has been used to examine the role of H1 and H3 phosphorylations in
      controlling chromosome condensation in the mouse FM3A cell line. We present
      evidence that (i) staurosporine inhibits the protein kinases that phosphorylate
      histone H1 during mitosis, (ii) staurosporine also inhibits the histone H3
      specific kinase, (iii) the inhibition of these kinase activities prevent cells
      from entering mitosis, and (iv) addition of staurosporine to cells already
      arrested at metaphase by nocodazole causes a rapid dephosphorylation of histones
      H1 and H3 and the decondensation of the metaphase chromosomes. The results show
      that the hyperphosphorylation of histone H1 and phosphorylation of histone H3 are
      required to maintain metaphase chromosomes in their condensed state.

PMID- 8144544
TI  - Purification and characterization of a novel species of ubiquitin-carrier
      protein, E2, that is involved in degradation of non-"N-end rule" protein
      substrates.
AB  - Ubiquitin-carrier proteins (E2s, ubiquitin-conjugating enzymes, UBCs) participate
      in proteolysis by catalyzing transfer of activated ubiquitin to the protein
      substrates, which are bound to specific ubiquitin-protein ligases (E3s). Yeast
      UBC2 (RAD6) and the mammalian E2(14kDa) bind to the ligase that recognizes and is
      involved in the degradation of certain free amino-terminal substrates ("N-end
      rule" substrates). As such proteins are rather scarce, the role of these E2s in
      general proteolysis is probably limited. Here, we report the purification and
      characterization of a novel 18-kDa species of E2 from rabbit reticulocytes.
      Unlike most members of the E2 family, this enzyme does not adsorb to anion
      exchange resin in neutral pH, and it is purified from the unadsorbed material
      (Fraction 1). Thus, it is designated E2-F1. Like all members of the E2 family, it
      generates a thiol ester with ubiquitin that serves as an intermediate in the
      conjugation reaction. Sequence analysis revealed a significant homology to many
      known species of E2s. The enzyme generates multiply ubiquitinated proteins in the
      presence of an E3 that has not been characterized yet. Most importantly, the
      ubiquitination via this E2 leads to the degradation of certain non-"N-end rule"
      substrates such as glyceraldehyde-3-phosphate dehydrogenase (Val at the NH2
      terminus) and to the ubiquitination and degradation of certain N-alpha-acetylated
      proteins such as histone H2A, actin, and alpha-crystallin. The enzyme is also
      involved in the conjugation and degradation of the tumor suppressor protein p53.

PMID- 8144545
TI  - Degradation of the tumor suppressor protein p53 by the ubiquitin-mediated
      proteolytic system requires a novel species of ubiquitin-carrier protein, E2.
AB  - The tumor suppressor protein p53 is extremely unstable in most cell lines. In
      contrast, many mutant and oncogenic species of the protein are stable. The
      degradation of p53 in vivo requires metabolic energy; however, the proteolytic
      system(s) involved have not been identified. The ubiquitin system has been
      implicated in the degradation of p53 in vitro. The degradation is stimulated
      significantly by the human papillomavirus (HPV) oncoprotein E6 that associates
      with p53 and facilitates conjugate formation and subsequent degradation. Complex
      formation between E6 and p53 is promoted by a cellular protein designated E6
      associated protein (E6-AP). Initial dissection of the conjugation process have
      demonstrated a role for the ubiquitin-activating enzyme, E1, but the ubiquitin
      carrier protein (E2, UBC) and the ubiquitin protein ligase, E3, have not been
      identified. In this study, we report that a novel species of ubiquitin-carrier
      protein designated E2-F1 (Blumenfeld, N., Gonen, H., Mayer, A., Smith, C.,
      Siegel, N.R., Schwartz, A.L., and Ciechanover, A. (1994) J. Biol. Chem. 269, 9574
      9581) is involved in the conjugation and degradation of p53. This E2 enzyme
      recognizes non-"N-end rule" protein substrates and appears to mediate their
      conjugation via a novel species of E3. The process of recognition appears to be
      selective; E2-F1 is not required for the conjugation and degradation of human N
      myc. The involvement of E2-F1 in the in vitro process appears to be
      physiologically meaningful and to reproduce the in vivo process; mutant species
      of p53 that do not interact with E6 and are stable in vivo are not recognized by
      the cell free system.

PMID- 8144546
TI  - Complementation of the interferon alpha response in resistant cells by expression
      of the cloned subunit of the interferon alpha receptor. A central role of this
      subunit in interferon alpha signaling.
AB  - A subunit of the interferon alpha receptor (IFN alpha R) that confers biologic
      response to and specific "binding" for IFN alpha 8 has recently been cloned. We
      have explored the biological consequences of expressing the cloned IFN alpha R
      subunit in human cells resistant to IFN alpha and in mouse cell lines
      nonresponsive to human IFN alpha. The expression of the cloned IFN alpha R
      subunit in the human IFN alpha-resistant K-562 cell line restored sensitivity to
      the antiviral effect of not only IFN alpha 8 but also IFN alpha 2 and IFN alpha
      Con1. In mouse L-929 cells the expression of the cloned receptor subunit markedly
      increased antiviral sensitivity to human type I IFNs. In either human K-562 or
      mouse L-929 cells these effects were observed without a detectable increase in
      the binding for any of the subtypes of IFN alpha tested. We propose that the
      cloned IFN alpha R subunit functions as a transducer subunit for the IFN alpha R.
      This concept is supported by the finding that the cloned receptor protein, when
      it is expressed in Cos cells, has an M(r) of 75 kDa, which is different from the
      main IFN alpha-binding proteins, the alpha and beta subunits of the IFN alpha R.
      This report also suggests that alterations at the receptor level could be
      involved in IFN alpha resistance in some cell lines.

PMID- 8144547
TI  - Transforming growth factor beta 1 stimulates type V collagen expression in bovine
      vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (SMCs) produce the bulk of the connective tissue of
      major arteries, including collagen types I, III, and V. Recently, we have shown,
      they also have the capacity to synthesize the alpha 1 chain of type XI, a
      collagen related to type V (Brown, K., Lawrence, R., and Sonenshein, G. (1991) J.
      Biol. Chem. 266, 23268-23273). Furthermore, expression of types V and XI collagen
      were coordinately regulated with respect to serum deprivation and cell density in
      a fashion distinct from that for types I and III. To begin to determine the
      factors that influence vascular SMC production of types V/XI collagen, we have
      examined the effects of transforming growth factor (TGF)-beta 1, a major
      modulator of connective tissue expression. In serum-deprived confluent cultures
      of bovine pulmonary artery SMCs, TGF-beta 1 treatment increased the steady-state
      levels of the mRNAs of collagen types V and XI, as well as of types I and III,
      elastin and fibronectin. The largest increase was seen for alpha 2(V)
      procollagen. The increase in alpha 2(V) mRNA was detectable by 12 h after
      addition of 2 ng/ml TGF-beta 1, and concentrations as little as 0.5 ng/ml were
      effective. A similar increase in alpha 2(V) mRNA levels was observed with SMCs
      derived from the aortic arch and carotid artery. Type V collagen protein was
      found to be elevated by TGF-beta 1 treatment in both the conditioned media and
      the cell layer associated fraction of pulse-labeled cultures. A slight decrease
      in SMC proliferation as judged by DNA content, [3H]thymidine incorporation, and
      steady-state levels of histone H3.2 mRNA resulted from TGF-beta 1 treatment.
      These results suggest that the elevated levels of TGF-beta 1 in the vessel wall
      during atherosclerosis may be, in part, responsible for the increase in type V
      collagen that typifies advanced fibrotic lesions.

PMID- 8144548
TI  - Membrane-induced helical conformation of an active candidacidal fragment of
      salivary histatins.
AB  - The conformational preference of the candidacidal C-terminal 16 residue fragment
      (9-24; G-Y-K-R-K-F-H-E-K-H-H-S-H-R-G-Y) of salivary histatin 5 was examined in
      water, methanol, and dimethyl sulfoxide solutions using 500 MHz two-dimensional
      NMR. Fourier transform infrared and CD spectroscopy were used to delineate its
      membrane-bound conformation in lipid vesicles. The peptide backbone and side
      chain proton resonance assignments were accomplished by two-dimensional total
      correlated and nuclear Overhauser effect (NOE) spectra. The coupling constant
      (JNH-C alpha H) values determined from the double quantum-filtered correlated
      spectra, temperature coefficients of NH chemical shifts (d delta/dT), 1H/2H
      exchange rates on amide resonances, and the set of NOE connectivities were used
      to delineate backbone conformational features. The high JNH-C alpha H values (>
      or = 7.4 Hz), absence of any characteristic NH-NH (i, i + 1) or C alpha H-C beta
      H (i, i + 3) NOE connectivities, high d delta/dT values (> or = 0.004), and the
      fast 1H/2H amide exchange suggest that the histatin peptide favors unfolded
      random conformations in aqueous solution at pH 3.8. In contrast, the JNH-C alpha
      H values (< or = 6.5 Hz), slow 1H/2H exchange, low d delta/dT values (< or =
      0.003) observed for amide resonances of residues 5-16, and the characteristic NH
      NH (i, i + 1), C alpha H-C beta H (i, i + 3) NOE connectivities, provide evidence
      for the presence of largely alpha-helical conformations in dimethyl sulfoxide,
      which mimics the polar aprotic membrane environment. In methanolic solutions,
      3(10)-helical conformations could exist as a minor population together with the
      major alpha-helical conformations. Fourier transform infrared spectroscopy and CD
      data indicate that lipid environments such as dimyristoylphosphatidylcholine
      vesicles could induce the peptide to fold into predominantly alpha-helical
      conformation. The results suggest that in dimethyl sulfoxide and
      dimyristoylphosphatidylcholine vesicles the candidacidal domain of salivary
      histatin 5 prefers a largely helical conformation, which could facilitate its
      interaction with the membrane of Candida albicans. The mechanism of antimicrobial
      action of this class of polypeptides appears to involve primarily electrostatic
      and hydrogen-bonding interaction of cationic and polar residues with the head
      groups of the plasma membranes of target cells.

PMID- 8144549
TI  - Regulation of heme oxygenase activity in Cyanidium caldarium by light, glucose,
      and phycobilin precursors.
AB  - Cyanobacteria, red algae, and cryptophytes contain phycobiliproteins which
      function as photosynthetic light-harvesting pigments. The chromophores of
      phycobiliproteins are phycobilins, open-chain tetrapyrroles that are synthesized
      from protoheme. The first step of phycobilin formation is the conversion of
      protoheme to biliverdin IX alpha in a reaction that is catalyzed by heme
      oxygenase. In the unicellular red alga, Cyanidium caldarium, light is required
      for the accumulation of phycobiliproteins. It has been reported previously that
      the synthesis of the apoprotein components of allophycocyanin and phycocyanin is
      induced by light in C. caldarium, that the phycobilin precursors, delta
      aminolevulinic acid (ALA), protoporphyrin IX, and protoheme can substitute for
      light, and that the regulation is exerted at the level of mRNA synthesis. We have
      determined that a key enzyme of phycobilin formation is induced by light in C.
      caldarium. Extractable heme oxygenase activity is low in dark-grown cells, and it
      increases approximately 6-fold during the first 24 h after the cells are
      illuminated. After 24 h, the activity decreases to a level approximately equal to
      the initial activity. Heme oxygenase is induced in unilluminated cells by
      administration of ALA. D-Glucose, which is known to inhibit phycocyanin
      accumulation in C. caldarium, inhibits the induction of heme oxygenase by light
      or ALA. Induction of heme oxygenase by light or ALA is blocked by cycloheximide,
      an inhibitor of cytoplasmic protein synthesis, but not by chloramphenicol, an
      inhibitor of chloroplast protein synthesis. Rifampicin, an inhibitor of algal
      chloroplast RNA synthesis, and gabaculine, a competitive inhibitor of ALA
      biosynthesis, block the induction of heme oxygenase by light but not by ALA.
      These results indicate that heme oxygenase in C. caldarium is induced by
      phycobilin precursors. The induction by light and the repression of the induction
      by D-glucose are probably indirect effects mediated by the effects of light and D
      glucose on phycobilin precursor formation. The results also indicate that heme
      oxygenase is encoded by a nuclear gene and is synthesized on cytoplasmic
      ribosomes.

PMID- 8144550
TI  - Single amino acid substitutions of alpha 1-antitrypsin that confer enhancement in
      thermal stability.
AB  - A recombinant alpha 1-antitrypsin variant which increased thermal stability was
      obtained from random mutagenesis followed by screening. The clone was identified
      as having a single mutation of Phe51-->Cys. Heat deactivation of purified
      recombinant alpha 1-antitrypsin produced in Escherichia coli revealed that the
      mutation slowed down the deactivation rate 10-fold at 57 degrees C, increasing
      thermal stability of recombinant protein to almost that of natural glycosylated
      plasma form. The mutant protein also exhibited increased stability against
      denaturant. The urea-induced unfolding monitored by the changes in fluorescence
      intensity at 360 nm showed that the mutation shifted midpoint of the transition
      from 1.9 M to 2.8 M. The mutation site is particularly interesting in that some
      genetic variants mapped at adjacent positions were shown previously to cause
      aggregation of the polypeptides, while the Phe51-->Cys mutation decreased
      aggregation rate significantly during heat deactivation. The association rate
      constant with porcine pancreatic elastase revealed that the mutation did not
      affect inhibitory activity significantly. The site identified may be critical for
      regulating stability of alpha 1-antitrypsin. Characterization of various single
      amino acid substitutions at position 51 suggests that volume and flexibility of
      hydrophobic side chain at the site are critical factors for enhancing the
      stability of alpha 1-antitrypsin.

PMID- 8144551
TI  - Cloning of the pka1 gene encoding the catalytic subunit of the cAMP-dependent
      protein kinase in Schizosaccharomyces pombe.
AB  - We have isolated Schizosaccharomyces pombe genes that confer sterility to the
      fission yeast cell when expressed from a multicopy plasmid. One of these genes
      strongly hybridized to a probe carrying the open reading frame of Saccharomyces
      cerevisiae TPK1, which encodes a catalytic subunit of the cAMP-dependent protein
      kinase (protein kinase A). This S. pombe gene, named pka1, has a coding potential
      of 512 amino acids, and the deduced gene product is 60% identical with the S.
      cerevisiae Tpk1 protein in the C-terminal 320 amino acids. Disruption of pka1
      slows cell growth but is not lethal. The resultant cells, however, are highly
      derepressed for sexual development, readily undergoing conjugation and
      sporulation in the absence of nitrogen starvation. They are, thus, phenotypically
      indistinguishable from the adenylyl cyclase-defective (cyr1-) cells previously
      characterized, except that the pka1- spores are retarded in germination, whereas
      the cyr1- spores are not. Disruption of pka1 is epistatic to a defect in cgs1,
      which encodes the regulatory subunit of protein kinase A. These results strongly
      suggest that the product of pka1 is a catalytic subunit of protein kinase A and,
      furthermore, that S. pombe has only one gene encoding it. This situation
      contrasts with the case of S. cerevisiae, in which three genes encode the
      catalytic subunits.

PMID- 8144552
TI  - Juvenile form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). A C-terminal
      extension causes instability but increases catalytic efficiency of arylsulfatase
      B.
AB  - A deficiency of the enzyme arylsulfatase B results in the lysosomal storage
      disorder Maroteaux-Lamy syndrome or mucopolysaccharidosis type VI. Severe,
      intermediate and mild forms of this autosomal recessively inherited disease can
      be clinically differentiated. To determine the molecular defect in a patient with
      the intermediate form of the disorder, DNA fragments generated from the patient's
      mRNA by reverse transcription and subsequent amplification by the polymerase
      chain reaction were subcloned and sequenced. The mRNA transcribed from one allele
      contains a 244-base pair deletion causing a frameshift and a truncation of the
      open reading frame. The C-terminal third of the encoded mutant polypeptide has a
      nonsense sequence. This mutation is due to a deletion of exon 5 in this allele. A
      silent A to G transition at nucleotide 1191 was present in the same allele, and
      the second allele was characterized by a T to C transition at nucleotide 1600
      causing a mutation of the translational stop codon to a glutamine codon (*534Q)
      and extending the encoded polypeptide by 50 amino acids. Stable expression of the
      *534Q allele in LTK- cells resulted in a mutant precursor 4 kDa larger than the
      wild-type precursor. The majority of the mutant precursor appears to be degraded
      before reaching the trans Golgi. This is consistent with an altered polypeptide
      structure, where a number of missing or masked epitopes were observed in an
      enzyme immunobinding assay using a panel of monoclonal antibodies.
      Immunoquantification analysis showed that epitopes were most likely masked, as
      missing epitopes could be reformed by binding the mutant protein to a polyclonal
      antibody of arylsulfatase B. It is suggested that the additional amino acids at
      the C terminus of the arylsulfatase B polypeptide induce a protein conformational
      change. *534Q mutant polypeptide escaping degradation is sorted to dense
      lysosomes. The mutant polypeptide has an approximately 9-fold higher catalytic
      efficiency than wild-type arylsulfatase B.

PMID- 8144553
TI  - Gelonin analogs with engineered cysteine residues form antibody immunoconjugates
      with unique properties.
AB  - We engineered the ribosome inactivating-protein gelonin (Gel) to generate a
      family of Gel analogs, each with a single unpaired cysteine residue. The cysteine
      sites coincide with surface-accessible loops in the probable three-dimensional
      structure of Gel, or with the positions of endogenous cysteine residues. In most
      cases, enzymatic activity in vitro was unaltered by this modification. The rGel
      analogs were conjugated via their unpaired cysteine residue to the anti-CD5
      antibody H65, or to H65 Fab and F(ab')2. Several rGel analogs formed
      immunoconjugates that were up to 6-fold more cytotoxic to antigen-bearing cells
      than those made with linker-modified rGel, whereas others were less potent. In
      the rat, the in vivo clearance rates of whole antibody conjugates correlated with
      their relative in vitro disulfide bond stability, and deconjugation to intact
      antibody and rGel was the predominant clearance mechanism. Fab conjugates to rGel
      analogs which differed in their in vitro disulfide bond stability had similar
      serum clearance rates, suggesting that clearance occurs mainly by removal of
      intact immunoconjugate from the serum, and is less dependent on deconjugation.
      Our results demonstrate that rGel analogs with a single cysteine at various
      positions on the solvent exposed surface are produced efficiently in Escherichia
      coli (>1 g/liter), and that the position of the cysteine greatly influences the
      potency and stability of the resulting immunoconjugates.

PMID- 8144554
TI  - Transport and accumulation of 1,5-anhydro-D-glucitol in the human erythroleukemia
      cell line K-562.
AB  - The transport and intracellular accumulation of 1,5-anhydro-D-glucitol (AG) was
      studied in the human erythroleukemia cell line K-562 by gas chromatography-mass
      spectrometry in conjunction with liquid scintillation spectrometry. K-562 cells
      contained 106 +/- 6 nM/10(6) cells of free AG, primarily in the cytosol. Addition
      of physiologic amounts of AG to the extracellular medium resulted in rapid
      intracellular incorporation of AG, with a half-saturation time of 5 s.
      Intracellular accumulation was linear for 2 h and subsequently reached
      saturation. AG uptake was temperature and concentration dependent with an
      apparent Km of 127 mM. AG uptake and accumulation was not inhibited by fructose,
      fucose, galactose, mannose, glucose, or 3-O-methyl-D-glucose and was less
      affected by cytochalasin B or phloretin than that of 2-deoxyglucose. Phloridzin
      did not affect AG uptake but did inhibit 2-deoxyglucose uptake. Efflux of AG from
      K-562 cells depended on external AG concentration alone and was not affected by
      extracellular glucose concentration. Intracellular AG concentration decreased
      rapidly and reached zero within 10 min following removal of AG from the external
      medium. We therefore propose that both transport and countertransport of AG in K
      562 cells are mediated by a specific carrier system.

PMID- 8144555
TI  - Transcriptional regulation of the C1 inhibitor gene by gamma-interferon.
AB  - Treatment of the hepatoma cell line, Hep3B, with gamma-interferon (IFN) enhanced
      expression of C1 inhibitor (C1INH) mRNA, primarily due to an enhanced
      transcription rate. Hep3B cells transfected with reporter constructs containing
      various regions of the C1INH gene between positions -1182 and +587, and
      stimulated with gamma-IFN, expressed increased levels of chloramphenicol
      acetyltransferase in the presence of the first intron and as few as 12 bases of
      the 5'-flanking region. However, a 66% reduction in the inducibility of the
      constructs was observed when the upstream region between -582 and -252 was
      eliminated. Successive deletions mapped the first intron IFN-responsive elements
      to a region between +368 and +410. The data indicate that both the upstream and
      the first intron sequences can independently enhance induction of C1INH gene
      expression. Examination of the immediate upstream sequence of the C1INH gene
      reveals the absence of a TATA box. The promoter of the C1INH gene was mapped to a
      region within 81 bases of the upstream sequence and the first exon. Further
      examination indicated two regions that were potentially important for promoter
      activity as follows: 1) a G-C-rich region from -81 to -49, and 2) an initiator
      element at -3 to +5. The results indicate that the upstream sequences including 
      81 to -49 and the H-DNA region between -48 and -17 are not necessary for promotor
      activity. The initiator element from -3 to +5 is sufficient and necessary for
      promoter function.

PMID- 8144556
TI  - Molecular characterization of the functionally distinct hemoglobins of the
      Antarctic fish Trematomus newnesi.
AB  - Antarctic fish of the family Nototheniidae usually have a single major hemoglobin
      (Hb 1), often a second, minor component (Hb 2, about 5% of the total), and traces
      of another component (Hb C, less than 1%). These are functionally similar Bohr
      and Root effect hemoglobins. All species of other highly endemic fish families so
      far investigated also have one single major hemoglobin. The hematological
      features of the nototheniid Trematomus newnesi are remarkably different. It is
      the only Antarctic species in which Hb 1 and Hb 2 display only a very weak Bohr
      effect and no Root effect. Perhaps consequentially, Hb C (the only component
      showing regulation of oxygen binding by protons and other effectors) is not
      present in traces but accounts for 20-25% of the total. The primary structure of
      the three hemoglobins of T. newnesi and of Root effect HbC present in trace
      amounts in another nototheniid (Pagothenia bernacchii) is discussed in
      relationship with oxygen binding and in terms of molecular and stereochemical
      models. The hemoglobin multiplicity, the oxygen binding features of Hb 1 and Hb
      2, and the presence of functionally distinct components, thus reveal that the
      oxygen transport of T. newnesi has unique characteristics.

PMID- 8144557
TI  - 3,5,3'-L-triiodothyronine (thyroid hormone)-induced protein-DNA interactions in
      the thyroid hormone response elements and cell type-specific elements of the rat
      growth hormone gene revealed by in vivo dimethyl sulfate footprinting.
AB  - The cell type-specific element and 3,5,3'-L-triiodothyronine (thyroid hormone)
      (T3) response element of the rat growth hormone gene act synergistically to
      produce cell type-specific, T3-regulated expression. Pit-1 is a pituitary cell
      type-specific transcription factor that binds the cell type-specific element and
      is essential to its activity. T3 receptors bind as homodimers and heterodimers to
      the T3 response element and are essential for its activity. Here, we report the
      use of ligation-mediated polymerase chain reaction in vivo dimethyl sulfate
      footprinting to study the effects of T3 on protein-DNA interactions in the rat
      growth hormone gene promoter in vivo. T3-responsive guanine methylation was
      detected only in and near the T3 response element and the Pit-1 binding sites.
      The results indicate that within 2 h, T3 induces occupancy of the T3 response
      element and Pit-1 sites by their respective trans-acting factors in vivo.

PMID- 8144558
TI  - Differential effects of translational inhibition in cis and in trans on the decay
      of the unstable yeast MFA2 mRNA.
AB  - Several observations in eukaryotic cells suggest that the processes of
      translation and mRNA turnover are interrelated. To understand this relationship,
      we examined the effects of translational inhibition on the decay of the unstable
      yeast MFA2 mRNA, which is degraded in a 5' to 3' direction following
      deadenylation (1). Although inhibition of translation in cis stabilizes several
      unstable mammalian transcripts, inhibiting translation of the MFA2 mRNA in cis,
      by the insertion of a large stem-loop structure in the 5'-untranslated region
      (UTR), did not affect the half-life, deadenylation rate, or appearance of
      specific decay intermediates. Therefore, efficient translational elongation on
      the MFA2 mRNA is not a requirement for the normal rate, or mechanism, of
      degradation of this transcript. In contrast, inhibition of translation in trans,
      by the addition of cycloheximide, stabilized the deadenylated form of MFA2 mRNA.
      Furthermore, the MFA2 transcripts that were not translated due to a stem-loop in
      the 5'-UTR were also stabilized in the presence of cycloheximide, suggesting that
      cycloheximide is likely to affect mRNA stability indirectly. These results
      suggest possible relationships between the mechanisms of mRNA decay and the
      translational process.

PMID- 8144559
TI  - Nuclear retention of the induced mRNA following amino acid-dependent
      transcriptional regulation of mammalian ribosomal proteins L17 and S25.
AB  - An amino acid starvation-induced mRNA, increased up to 4-fold in the absence of
      amino acids, was identified previously as rat 60 S subunit ribosomal protein L17.
      The data presented here demonstrate that among ribosomal proteins, L17, as well
      as the smaller subunit ribosomal protein S25, are uniquely regulated by amino
      acid deprivation of cells; the increase in L17 and S25 mRNA content in response
      to substrate starvation is not shared by the 11 other ribosomal proteins tested.
      When rat Fao hepatoma cells were incubated in the presence of actinomycin D, the
      L17 mRNA level decayed below the basal level, regardless of medium amino acid
      content, and nuclear run-off assays confirmed that nutrient starvation leads to
      enhanced transcription of the L17 ribosomal protein gene. Likewise, the induction
      of S25 mRNA also was prevented in the presence of actinomycin D. Furthermore, the
      induction of L17 and S25 mRNA content was blocked by cycloheximide, demonstrating
      the requirement for a newly synthesized protein in the signaling pathway.
      Northern analysis with RNA isolated from cytoplasmic, polysomal, and nuclear
      enriched fractions indicated that the starvation-dependent increase in the S25
      and L17 mRNAs is retained within the nucleus and not is available for
      translation. Amino acid refeeding of the cells caused the translocation of the
      stored nuclear mRNAs to the polysomal fraction.

PMID- 8144560
TI  - In vitro assembly of an anion-stimulated ATPase from peptide fragments.
AB  - The oxyanion-translocating ATPase encoded by the ars operon of plasmid R 773
      confers resistance to antimonials and arsenicals in Escherichia coli by extrusion
      of the oxyanions from the cells. The catalytic subunit, the ArsA protein, is an
      oxyanion-stimulated ATPase with two nucleotide binding consensus sequences, one
      in the N-terminal half and one in the C-terminal half of the protein. In this
      report subclones of the arsA gene were constructed to produce polypeptide
      fragments of the ArsA protein. By themselves none of the fragments exhibited
      anion-stimulated ATPase activity. Denaturation and renaturation of mixtures of N-
      and C-terminal polypeptides that between them comprised an entire ArsA protein
      resulted in active ATPase complexes.

PMID- 8144561
TI  - Expression of Escherichia coli folylpolyglutamate synthetase in the Chinese
      hamster ovary cell mitochondrion.
AB  - Chinese hamster ovary (CHO) cell transfectants expressing Escherichia coli
      folylpoly-gamma-glutamate synthetase (FPGS) activity solely in their cytosol lack
      mitochondrial folylpolyglutamates and are auxotrophic for glycine. Addition of a
      mammalian mitochondrial leader sequence targeted E. coli FPGS to the mitochondria
      of these cells. Mitochondrial expression of FPGS restored mitochondrial
      folylpolyglutamate pools and overcame the glycine requirement.
      Pteroyltriglutamates functioned as effectively as the longer glutamate chain
      length folates found in wild type CHO cells in the metabolic cycle of glycine
      synthesis provided they were located in the mitochondria. Although
      folypolyglutamates cannot enter the mitochondria, mitochondrial
      folylpolyglutamates can be released without prior hydrolysis and CHO
      transfectants expressing E. coli FPGS activity solely in the mitochondria
      possessed normal cytosolic folylpolyglutamate pools. The proportion of cellular
      folate in the mitochondrion is governed by competition between mitochondrial and
      cytosolic FPGS activities.

PMID- 8144562
TI  - Role of folylpolyglutamate synthetase in the metabolism and cytotoxicity of 5
      deazaacyclotetrahydrofolate, an anti-purine drug.
AB  - Chinese hamster ovary (CHO) cells expressing human and Escherichia coli
      folylpolyglutamate synthetase (FPGS) activities were used as models to study
      factors regulating the cytotoxicity and metabolism of 5
      deazaacyclotetrahydrofolate (DATHF), an anti-purine agent that requires
      conversion to polyglutamate forms to be a potent inhibitor of its target enzymes.
      The sensitivity of cells continuously exposed to DATHF was not influenced by FPGS
      activity. After short term exposure to DATHF, cells expressing higher levels of
      human FPGS were more sensitive to the drug while cells expressing low levels were
      resistant. Cells expressing E. coli FPGS solely in the cytosol were resistant to
      DATHF and accumulated only low levels of the drug. Expression of E. coli FPGS in
      the mitochondria of these cells restored drug sensitivity and cytosolic drug
      accumulation. DATHF is extensively metabolized in the mitochondria of mammalian
      cells and, despite an inability to enter the mitochondria, folylpolyglutamates
      and DATHF polyglutamates formed in the mitochondria are released into the cytosol
      without prior hydrolysis. DATHF was not solely an inhibitor of de novo purine
      biosynthesis but also inhibited glycine synthesis in the cell.

PMID- 8144563
TI  - Bactericidal potency of hydroxyl radical in physiological environments.
AB  - Rates of radiolytic inactivation of bacteria suspended in N2O-saturated solutions
      were dramatically increased over normal background levels when the media
      contained chloride or bicarbonate ions. The bacteria could be protected from this
      enhanced toxicity by the addition of free radical scavengers (ethanol, ascorbate,
      hydrogen peroxide, mannitol, glucose, EDTA, picolinic acid), indicating that the
      lethal reactions were extracellular in origin. Prior irradiation of chloride
      containing solutions led to formation of hypochlorous acid, which was identified
      by detection of ring-chlorinated products when reacted with fluorescein.
      Prolonged irradiation of other solutions did not lead to accumulation of
      bactericidal agents; however, irradiation of bicarbonate-containing solutions in
      the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) led to
      formation of the EPR-detectable DMPO.CO3- adduct. The results are interpreted in
      terms of formation of secondary radicals, among which the carbonate and chlorine
      radicals are uniquely toxic to bacteria. From rate comparisons of the solution
      components, it was concluded that the reactions involving chloride ion are
      unlikely to be expressed in biological environments, but that the CO3- radical
      could be an important intermediary oxidant in peroxide-inflicted cellular damage,
      particularly in spatially confined environments such as the leukocyte phagosome.

PMID- 8144564
TI  - Identification, partial purification, and characterization of a novel
      phospholipid-dependent and fatty acid-activated protein kinase from human
      platelets.
AB  - A novel lipid-dependent protein kinase in human platelets was partially purified
      and characterized. This enzyme was calcium-independent and was selective for
      phosphatidic acid as a cofactor/activator with initial activation observed at
      approximately 2 mol % and peak activity achieved at 4 mol % phosphatidic acid. In
      the presence of phosphatidylserine, enzyme activation was observed with
      concentrations of phosphatidic acid as low as 0.5 mol % with peak activity at 2
      mol %. Other anionic phospholipids also activated the enzyme but to a lesser
      extent and with less potency. Enzyme activity was independent of diacylglycerol
      or phorbol esters and the enzyme did not bind [3H]phorbol dibutyrate. In a
      soluble protein kinase assay, the enzyme was activated by cis-unsaturated fatty
      acids with maximum activation occurring at 5-10 microM sodium oleate. Western
      blot analysis showed that this enzyme did not cross-react immunologically with
      antibodies raised against the currently identified isoenzymes of protein kinase
      C. A number of additional biochemical criteria distinguished this enzyme from
      known isoenzymes of protein kinase C. These biochemical and immunologic data
      define a novel lipid-dependent protein kinase in human platelets. The role of
      this enzyme in signal transduction as a phosphatidic acid-activated enzyme and as
      a possible target for cis-unsaturated fatty acids is discussed.

PMID- 8144565
TI  - Characterization of the metal centers of the Ni/Fe-S component of the carbon
      monoxide dehydrogenase enzyme complex from Methanosarcina thermophila.
AB  - Methanosarcina thermophila contains a multienzyme complex called the carbon
      monoxide dehydrogenase complex, which has been resolved into a nickel/iron-sulfur
      and a corrinoid/iron-sulfur component. This complex plays a central role in
      acetoclastic methanogenesis. The Ni/Fe-S component catalyzes CO oxidation and has
      been proposed to be involved in cleavage of acetyl-CoA into its methyl, carbonyl,
      and CoA moieties. In the work reported here, three metal centers in the Ni/Fe-S
      component were characterized by electron paramagnetic resonance (EPR)
      spectroscopy and spectroelectrochemistry and pre-steady state kinetics. Center A
      contains nickel and iron and forms an EPR active adduct with CO, which is called
      the NiFeC species. The EPR spectrum of the NiFeC species has g values of 2.059,
      2.051, and 2.029 and is observable at temperatures as high as 150 K. This signal
      had previously been observed only in the carbon-monoxide dehydrogenase complex of
      M. thermophila and the acetyl-CoA synthase from acetate-producing bacteria.
      Incubation of the CO-reduced Ni/Fe-S component with acetyl-CoA resulted in an
      increase in intensity of the NiFeC signal, which supports a role for the
      component in the cleavage of acetyl-CoA. Generation of the NiFeC EPR signal
      occurs with a rate constant of 0.4 s-1, a result that demonstrates the kinetic
      competence of this species in the acetyl-CoA cleavage reaction but rules it out
      as the site of oxidation of CO to CO2. Center B is likely to be a [4Fe-4S]2+/1+
      center with g values of 2.04, 1.93, and 1.89 (gav = 1.95) and a standard
      reduction potential (E'0) of -444 mV. At potentials less than -500 mV, another
      EPR signal develops that appears to originate from another state of Center B.
      Center C is a fast relaxing center with g values of 2.02, 1.88, and 1.71 (gav =
      1.87) and an E'0 of -154 mV.

PMID- 8144566
TI  - Effect of ADP-ribosylation factor amino-terminal deletions on its GTP-dependent
      stimulation of cholera toxin activity.
AB  - It has been proposed that the amino-terminal domain of ADP-ribosylation factor
      (ARF) is critical for its stimulation of cholera toxin ADP-ribosyltransferase
      activity. In this study, recombinant ARF1 (rARF1), r delta 13ARF1 (recombinant
      ARF1 lacking the first 13 amino acids) and rPKA14ARF1 (recombinant ARF1 in which
      the first 14 amino acids were replaced by the first 7 amino acids of the cAMP
      dependent protein kinase catalytic subunit) were used to assess the effect of the
      amino terminus on the ability of ARF to enhance ADP-ribosylation of agmatine by
      the cholera toxin A subunit. The GTP-dependent ARF activities of r delta 13ARF1
      and rPKA14ARF1 were similar to that of rARF1, whereas the GTP requirement for
      half-maximal activation of cholera toxin A, was somewhat higher for rARF1 than it
      was for r delta 13ARF1 and rPKA14ARF1. These results are consistent with the view
      that the amino terminus of ARF1 is not critical for its action as a GTP-dependent
      activator of cholera toxin.

PMID- 8144567
TI  - Transport of the glutathione-methylmercury complex across liver canalicular
      membranes on reduced glutathione carriers.
AB  - Methylmercury transport across liver canalicular membranes into bile, a major
      route of excretion of this toxic compound, is dependent upon intracellular GSH,
      and a glutathione-methylmercury complex (CH3Hg.SG) has been detected in liver
      tissue and bile. To examine whether the CH3Hg.SG complex is itself transported
      across the canalicular membrane and to identify the transport system involved,
      studies were performed in isolated rat liver canalicular plasma membrane
      vesicles. Uptake of CH3(203)Hg.SG (10 microM) into an osmotically active space
      was temperature-sensitive and unaffected by either ATP (5 mM) or an inwardly
      directed Na+ gradient (100 mM); however, CH3Hg.SG uptake was enhanced by a
      valinomycin-induced K+ diffusion potential (inside-positive) indicating that its
      transport was electrogenic. Transport of CH3Hg.SG exhibited saturation kinetics
      with both high affinity (Km = 12 +/- 2 microM, Vmax = 0.23 +/- 0.02 nmol.mg-1.20
      s-1) and low affinity (Km = 1.47 +/- 0.22 mM, Vmax = 1.23 +/- 0.14 nmol.mg-1.20 s
      1) components. Uptake of this complex was inhibited by GSH, the GSH analog
      ophthalmic acid, S-methyl, S-ethyl, S-butyl, S-hexyl, S-octyl, and S
      dinitrophenyl glutathione, but not by GSSG, bile acids, amino acids, and P
      glycoprotein inhibitors. Furthermore, GSH competitively inhibited (Ki = 83
      microM) and trans-stimulated CH3Hg.SG uptake into the canalicular vesicles. These
      studies provide the first kinetic characterization of a transport system for
      glutathione-mercaptides and indicate that CH3Hg.SG is not a substrate for the ATP
      dependent, canalicular GSSG or glutathione S-conjugate carriers, but appears to
      be a substrate for canalicular carriers that also transport GSH. Because efflux
      systems for GSH are found in all mammalian cells, transport of glutathione-metal
      complexes by such carriers may be a common mechanism for the removal of
      methylmercury and possibly other metals from cells.

PMID- 8144568
TI  - Stabilization of an active dimeric form of the epidermal growth factor receptor
      by introduction of an inter-receptor disulfide bond.
AB  - Populations of the epidermal growth factor receptor (EGFR) with both high and low
      affinity for EGF are found on the surface of cells. It has been hypothesized that
      the high-affinity state of the EGFR represents the receptor dimer and that this
      is also the kinase-active form. We describe here studies aimed at addressing this
      question directly. To stabilize homodimers of EGFR, we have generated a mutated
      form of the receptor by inserting a cysteine residue in the extracellular
      juxtamembranous region, in order to cross-link the extracellular domains of two
      receptors via disulfide bond formation. The mutation resulted in ligand-induced
      appearance of covalently linked EGF receptor dimers and, in parallel, increased
      the number of high-affinity receptors present on the surface of cells expressing
      the mutated EGFR. Comparison of the tyrosine kinase activity of the covalently
      linked dimeric and the monomeric forms of the EGF receptor, separated by sucrose
      density gradient centrifugation, showed that the dimer was significantly more
      active than monomer in the phosphorylation of exogenous substrate. We conclude
      that the dimeric form of the EGF-receptor represents the active form, and that
      dimer formation is associated with the appearance of high-affinity binding EGF
      receptors on the cell surface.

PMID- 8144569
TI  - Specificity of the binding interaction between human serum amyloid P-component
      and immobilized human C-reactive protein.
AB  - C-reactive protein (CRP) and serum amyloid P-component (SAP) are two members of a
      group of plasma proteins termed pentraxins, which are composed of five identical
      noncovalently linked subunits that display Ca(2+)-dependent binding to a wide
      variety of substrates. Purified human SAP binds to CRP, only when the latter is
      immobilized, in a Ca(2+)-dependent manner under physiological conditions.
      Externally labeled SAP rapidly binds to two distinct forms of immobilized CRP
      (direct and phosphorylcholine captured) with a relatively high affinity (KD = 5
      nM) at a molar ratio of specifically bound SAP/CRP = 0.3. Studies of binding
      inhibition using monoclonal antibodies to CRP or synthetic peptides of CRP
      revealed that residues 134-148 and the COOH-terminal region (residues 191-206)
      were recognized by SAP. A fragment of CRP consisting of the COOH-terminal 60
      residues within each subunit was also selectively bound by SAP. The ability of
      immobilized CRP to bind SAP was distinguished from CRP's lectin-like binding
      reactivity since deglycosylated SAP retained its binding reactivity for CRP and
      sugars that inhibit CRP's lectin-like binding activity failed to inhibit binding.
      A peptide from trypsin digested SAP composed of residues 144-199 retained CRP
      binding activity, implicating the COOH-terminal region of SAP as the CRP
      recognition site.

PMID- 8144570
TI  - Differential regulation of cAMP-mediated gene transcription by m1 and m4
      muscarinic acetylcholine receptors. Preferential coupling of m4 receptors to Gi
      alpha-2.
AB  - We have used a luciferase reporter gene under the transcriptional control of a
      cAMP response element as a sensitive monitor of the regulation by muscarinic
      acetylcholine receptors (mAChRs) of intracellular cAMP levels and cAMP-regulated
      gene expression. Treatment with the muscarinic agonist carbachol results in an
      increase in luciferase activity in JEG-3 cells transiently transfected with mouse
      m1 (8-10-fold) and chick m4 (3-5-fold) mAChRs. Control experiments indicate that
      these responses are not due to a calcium-mediated pathway and are dependent upon
      a functional protein kinase A. The m1 and m4 responses are not sensitive to
      pertussus toxin and the m4 response was potentiated by it. Thus, these responses
      do not result from direct stimulation of adenylate cyclase by beta gamma subunits
      released from pertussis toxin-sensitive G-proteins. Atropine treatment of cells
      transfected with high levels of m4 mAChR, but not m1, causes an elevation in
      basal levels of cAMP response element-mediated luciferase expression in the
      absence of agonist. This suggests that the m4 receptor is spontaneously active
      and can cause constitutive inhibition of adenylyl cyclase that is relieved by
      atropine treatment. Surprisingly, the m4 receptor exhibits little if any agonist
      induced inhibition of luciferase expression at either low or high levels of
      receptor expression. JEG-3 cells express Gi alpha-1 and Gi alpha-3 but not Gi
      alpha-2. Cotransfection of Gi alpha subunits with m4 demonstrates that the m4
      receptor requires Gi alpha-2 for optimal agonist-mediated inhibition. Even in the
      presence of Gi alpha-2, high levels of receptor increased luciferase expression
      at high concentrations of agonist. Thus, the m4 mAChR can undergo a switch in
      functional coupling from inhibition to stimulation of adenylyl cyclase. This
      switch is dependent on the level of receptor expression, the subtypes of G
      proteins coexpressed with the receptor, and the concentration of agonist.
      Furthermore, we demonstrate that the Gi alpha-2 G-protein alpha subunit
      preferentially couples the m4 mAChR to inhibition of adenylyl cyclase in JEG-3
      cells.

PMID- 8144571
TI  - The upstream repression sequence from the yeast enolase gene ENO1 is a complex
      regulatory element that binds multiple trans-acting factors including REB1.
AB  - Cis-acting sequences that modulate ENO1 URS (upstream repression site) element
      activity were identified by base pair substitution mutagenesis. Base substitution
      mutations within three distinct regions of the 125-base pair URS element caused
      partial loss of URS activity in vivo. A URS element containing all three
      mutations was inactive. A binding site for the yeast REB1 protein was identified
      near the 5' terminus of the ENO1 URS element. Base substitution mutations that
      disrupted REB1 binding in vitro caused a 30% loss of URS activity in vivo. A
      second DNA binding activity was identified which also bound near the 5' terminus
      of the URS element. This latter binding activity was not antigenically related to
      REB1 nor was binding of this activity affected by base substitution mutations
      that abolished REB1 binding. Base substitution mutations within a second region
      of the ENO1 URS element caused a 38% loss of URS activity in vivo. The nucleotide
      sequence of this latter region is very similar to essential sequences within the
      URS elements from the yeast CAR1 and SSA1 genes, respectively. Base substitution
      mutations within a third region near the 3' terminus of the ENO1 URS element
      caused a 70% loss of URS activity in vivo. These latter sequences bound a
      partially purified factor that was distinct from REB1. These results showed that
      ENO1 URS element activity was modulated by multiple cis-acting sequences that
      bound distinct trans-acting factors.

PMID- 8144572
TI  - Differential regulation of Hsp70 subfamilies by the eukaryotic DnaJ homologue
      YDJ1.
AB  - In Saccharomyces cerevisiae Ydj1p, a DnaJ homolog, is localized to the cytosol
      with the Ssa and Ssb Hsp70 proteins. Ydj1p helps facilitate polypeptide
      translocation across mitochondrial and endoplasmic reticulum membranes (Caplan,
      A. J., Cyr, D. M., and Douglas, M. G. (1992) Cell 71, 1143-1155) and can directly
      interact with Ssa1p to regulate chaperone activity (Cyr, D. M., Lu, X., and
      Douglas, M. G. (1992) J. Biol. Chem. 267, 20927-20931). In this study, the role
      of Ydj1p in modulating ATP-dependent reactions catalyzed by Ssa and Ssb Hsp70
      proteins has been examined using purified components and compared with that of
      other Hsp70 homologs BiP and DnaK. Ssa1p, Ssa2p, and Ssb1/2p all formed stable
      complexes with the mitochondrial presequence peptide, F1 beta(1-51). ATP alone
      had only modest effects on polypeptide complex formation with Ssa1p and Ssa2p,
      but prevented the majority of polypeptide binding to BiP and DnaK. ATP by itself
      also reduced polypeptide binding to Ssb1/2p to a level that was intermediate
      between that observed for the Ssa Hsp70 proteins tested and BiP and DnaK. ATP
      hydrolysis by Ssa1p, Ssa2p, and Ssb1/2p occurred at similar rates. Ydj1p was a
      potent modulator of the both the ATPase and polypeptide binding activities of
      Ssa1p and Ssa2p. In contrast, Ydj1p had little effect on the ATPase and
      polypeptide binding activity of Ssb1/2p. Therefore the chaperone-related
      activities of Ssa and Ssb Hsp70 proteins exhibit significant differences in
      sensitivity to ATP and YDJ1p. These data indicate that regulation of Hsp70
      activity by DnaJ homologs can be specific. The specificity of interactions
      between Ydj1p and the Ssa and Ssb Hsp70 proteins observed could contribute in
      determining the functional specificity of these chaperones in the cytosol. In
      related experiments, F1 beta(1-51) was found to reduce the extent to which Ydj1p
      stimulated Ssa1p ATPase activity. This effect correlated with the formation of F1
      beta(1-51).Ssa1p complexes. We propose that intramolecular communication between
      the polypeptide binding, ATPase and DnaJ regulatory domains on Ssa1p plays a role
      in the regulation of chaperone activity.

PMID- 8144573
TI  - Human neutrophil phagocytic granules contain a truncated soluble form of the
      Alzheimer beta/A4 amyloid precursor protein (APP).
AB  - We have characterized the molecular species and subcellular distribution of
      Alzheimer beta/A4 amyloid precursor protein (APP) in neutrophilic granulocytes
      purified from human peripheral blood. APP was readily detectable in these cells.
      Immunochemical analysis with a panel of antibodies revealed that this APP species
      lacked the transmembrane and cytoplasmic domains previously demonstrated in cell
      associated APP. However, it contained a protease inhibitor domain of the Kunitz
      type, indicating that neutrophil APP is a potent inhibitor of certain serine
      proteases. Upon subcellular fractionation, APP was primarily localized to
      azurophilic granules, which are neutrophil-specific phagocytic organelles
      assigned to enzymatic digestion of invading microbes and dead or injured tissue.
      Apparently, in the neutrophil, a nonsecretory organelle stores truncated, soluble
      APP, a species previously found only in blood plasma and cerebrospinal fluid or
      in conditioned medium of cultured cells. Soluble APP in neutrophils may therefore
      have intracellular functions in addition to its previously described
      extracellular functions. These findings also indicate that there are previously
      uncharacterized cell-specific differences in processing, trafficking, and storage
      of the APP molecule. Finally, the precise subcellular localization of APP to
      neutrophil-specific phagocytic organelles is suggestive of a role for APP in the
      nonimmunological host defense.

PMID- 8144574
TI  - Hepatocyte growth factor specifically binds to sulfoglycolipids.
AB  - Hepatocyte growth factor (HGF) is a heparin-binding pleiotropic factor that acts
      on a variety of epithelial cells. The interaction of human HGF with glycolipids
      was studied by overlaying them with 125I-HGF on thin layer chromatograms and by a
      solid-phase assay using lipids adsorbed on microtiter plates. Among various
      glycolipids tested, HGF was found to bind to sulfoglycolipids, including
      galactosylceramide sulfate (SM4), lactosylceramide sulfate (SM3), and
      gangliotriaosylceramide bis-sulfate. In contrast, HGF failed to bind to
      gangliosides or neutral glycolipids. HGF binding to SM4 was strongly inhibited by
      dextran sulfate, heparin, and fucoidan, whereas neither keratan sulfate nor
      hyaluronic acid had any inhibitory activity. When glycolipids from a renal cancer
      cell line, SMKT-R3, which overexpresses sulfoglycolipids, were developed on a
      thin layer chromatogram, SM4 and SM3 were the only glycolipids that bound HGF. We
      further examined the effect of the incorporation of glycolipids into SMKT-R3
      cells on HGF binding to the cells. The incorporation of SM4 into the cells
      enhanced HGF binding to SMKT-R3 cells, while that of galactosylceramide, a
      precursor of SM4, had no effect. These observations indicated that SM4
      exogenously incorporated into the cell membranes could react with HGF and
      suggested that endogenous sulfoglycolipids on SMKT-R3 cells might function as
      reservoirs for HGF.

PMID- 8144575
TI  - Endocytosis and degradation of the yeast uracil permease under adverse
      conditions.
AB  - Yeast uracil permease follows the secretory pathway to the plasma membrane and is
      phosphorylated on serine residues in a post-Golgi compartment. The protein was
      found to be rather stable in growing cells, but its turnover rate (half-life of
      about 7 h) was much faster than that of most yeast proteins. Several adverse
      conditions triggered the rapid degradation of uracil permease, and so a loss of
      uracil uptake. Turnover was rapid when yeast cells were starved of either
      nitrogen, phosphate, or carbon, and as they approached the stationary growth
      phase. Rapid permease degradation was also promoted by the inhibition of protein
      synthesis. The degradation of uracil permease in response to several stresses was
      strikingly slower in the two mutants, end3 and end4, that are deficient in the
      internalization step of receptor-mediated endocytosis. Thus, internalization is
      the first step in the permease degradative pathway. Uracil permease is degraded
      in the vacuole, since pep4 mutant cells lacking vacuolar protease activities
      accumulated large amounts of uracil permease, which was located within the
      vacuole by immunofluorescence. We have yet to determine whether adverse
      conditions enhance permease endocytosis and subsequent degradation or divert
      internalized uracil permease from a recycling to a degradative pathway.

PMID- 8144576
TI  - Assembly of Bcl-2 into microsomal and outer mitochondrial membranes.
AB  - Bcl-2 is thought to associate spontaneously with membranes via a carboxyl
      terminal hydrophobic domain by a mechanism analogous to that of cytochrome b5. We
      have examined the association of Bcl-2 with a variety of highly purified
      intracellular membranes in vitro. Fusion proteins were used to assess directly
      the role of the carboxyl-terminal hydrophobic domain of Bcl-2 in membrane
      association. Although this domain of Bcl-2 was sufficient to promote the
      association of a normally cytosolic polypeptide with either microsomal or
      mitochondrial membranes additional nonhydrophobic amino-terminal residues were
      required for membrane integration. Furthermore, direct comparison of membrane
      binding of Bcl-2 and cytochrome b5 revealed that similar to cytochrome b5,
      membrane targeting of Bcl-2 was not dependent on protease-sensitive components of
      the recipient membranes. In competition experiments, cytochrome b5 demonstrated
      the expected preference for integration into endoplasmic reticulum membranes. In
      contrast, the data presented here suggest that Bcl-2 is targeted to the
      cytoplasmic surface of multiple intracellular membranes, both in vitro and in
      human leukemic cells.

PMID- 8144577
TI  - Functional effect of phosphorylation of the photoreceptor phosphodiesterase
      inhibitory subunit by protein kinase C.
AB  - In rod outer segments the light activation of cGMP phosphodiesterase (PDE alpha
      beta gamma 2) is accomplished by removal of the gamma inhibitory subunit (PDE
      gamma) from the PDE alpha beta catalytic subunits. A light activation of the
      inositol signaling pathway also occurs, but there is little information linking
      these two signal transduction pathways. Here we report that protein kinase C
      (PKC) purified from bovine rod outer segment phosphorylates the bovine PDE gamma
      with incorporation of 0.9 +/- 0.1 mol of phosphate/mol of PDE gamma.
      Phosphorylation of PDE gamma increases its ability to inhibit PDE alpha beta
      catalytic activity (trypsin-activated PDE, tPDE) with an IC50 for phosphorylated
      PDE gamma of 26 +/- 4 pM and an IC50 of 60 +/- 5 pM for unphosphorylated PDE
      gamma. Inhibition of tPDE by PDE gamma is characterized by two values of Kd, Kd1
      = 34 pM and Kd2 = 760 pM. Phosphorylation of PDE gamma by PKC eliminates the
      functional heterogeneity of the PDE gamma population resulting in a single value
      of Kd = 23 pM. Free PDE gamma (without PDE alpha beta catalytic subunits) is a
      better substrate for PKC than PDE gamma in a complex with PDE alpha beta.
      Phosphorylation of free PDE gamma by PKC is characterized by a value of Vmax =
      1,550 +/- 148 units/mg (Km = 21.0 +/- 1.9 microM). In contrast, phosphorylation
      of PDE gamma in PDE alpha beta gamma 2 complex has two values of Vmax, Vmax1 =
      0.3 +/- 0.1 units/mg of PDE gamma (Km1 = 0.4 +/- 0.2 microM) and Vmax2 = 0.7 +/-
      0.2 units/mg of PDE gamma (Km2 = 4.6 +/- 0.9 microM). ROS PKC phosphorylates
      Thr35 in PDE gamma. We have previously reported (Morrison, D. F., Rider, M. A.,
      and Takemoto, D. J. (1987) FEBS Lett. 222, 266-270; Lipkin, V. M., Udovichenko,
      I. P., Bodarenko, V. A., Yurovskaya, A. A., Telnykh, E. V., and Skiba, N. P.
      (1990) Biomed. Sci. (Lond.) 1, 305-308) that the central fragment of PDE gamma
      (24-45) is responsible for binding to PDE catalytic subunits. The new data
      suggests that this region of PDE gamma also includes the site for phosphorylation
      by PKC and that phosphorylation increases the ability of PDE gamma to inhibit PDE
      catalytic activity. This altered regulation of visual transduction may play a
      role in desensitization or light adaptation.

PMID- 8144578
TI  - The effects of deletion of the amino-terminal helix on troponin C function and
      stability.
AB  - Troponin C has a 14-residue alpha-helix at the extreme amino terminus (the N
      helix) which is absent in calmodulin. To learn the significance of this region in
      troponin C, residues 1-14 were deleted using site-directed mutagenesis. Analysis
      of the mutant troponin C (delta 14-TnC) showed that deletion of the N-helix did
      not alter the secondary structure of troponin C. Like wild type troponin C, it
      exhibited Ca(2+)-dependent conformational changes based on electrophoretic
      mobility and increases in alpha-helix content. The thermal stability of delta 14
      TnC, however, was 20 degrees C lower than wild type troponin C in the presence or
      absence of divalent cations because of destabilization of the amino-terminal
      domain. To determine the functional consequences of the deletion, its ability to
      relieve troponin I and IT inhibition of the actomyosin ATPase was assayed. The
      results show that the mutant could relieve troponin I inhibition in the presence
      and absence of Ca2+ but could relieve troponin IT inhibition only to 45-50% of
      the wild type level, even at high concentrations. Also, the calcium affinity of
      the low affinity sites is reduced as evidence by the 2.4-2.8-fold increase in
      Ca2+ concentration required to achieve half-maximal activation of the MgATPase
      and calcium titration of the metal-induced conformation monitored by far UV
      circular dichroism measurements. In addition, the N-helix is required for the
      full conformational change to take place upon the binding of Ca2+, but not Mg2+,
      to the high affinity sites. The results indicate that the N-helix of troponin C
      is important for the stability of troponin C and may play a vital role in the
      Ca(2+)-switching mechanism.

PMID- 8144579
TI  - Isolation of a mouse Golgi mannosidase cDNA, a member of a gene family conserved
      from yeast to mammals.
AB  - The amino acid sequence of the specific alpha-mannosidase involved in N
      oligosaccharide processing in Saccharomyces cerevisiae was found to have a high
      degree of similarity to the deduced amino acid sequence of a rabbit liver alpha
      mannosidase partial cDNA, demonstrating that processing mannosidases have been
      conserved through eukaryotic evolution. Regions of sequence identity were chosen
      to design degenerate oligonucleotide primers that can be used to prepare probes
      using the polymerase chain reaction (PCR) for cloning processing mannosidases
      from other eukaryotes. Using these primers for PCR with mouse liver cDNA as
      template, two related but distinct PCR products were obtained. The amino acid
      sequences of PCR1 and PCR2 were 88 and 65% identical with the corresponding
      sequence of the rabbit enzyme, respectively. Southern blot analysis of mouse
      genomic DNA using PCR1 and PCR2 as probes revealed that they are derived from two
      different genes, indicating the existence of a mammalian mannosidase gene family
      with at least two members. Using PCR2 as a probe, a novel mouse cDNA was isolated
      from a 3T3 cDNA library. It contains an open reading frame which encodes a type
      II membrane protein of 73 kDa with a cytoplasmic region of about 35 amino acids,
      a Ca2+ binding consensus sequence, and a single N-glycosylation site. Northern
      blot analysis of mouse tissues and L cells revealed tissue-specific expression of
      multiple transcripts, ranging in size from 4.2 to 8.5 kilobases, that suggests a
      complex pattern of gene regulation. Transient expression of the influenza
      hemagglutinin epitope-tagged cDNA in COS cells followed by indirect
      immunofluorescence with monoclonal antibody 12CA5 showed that the cloned
      mannosidase is primarily localized in a juxtanuclear position corresponding to
      the Golgi. The C-terminal domain lacking the putative transmembrane region was
      shown to have alpha-mannosidase activity when expressed in COS cells as a
      secreted Protein A fusion product.

PMID- 8144580
TI  - Isolation and expression of murine and rabbit cDNAs encoding an alpha 1,2
      mannosidase involved in the processing of asparagine-linked oligosaccharides.
AB  - We have isolated a full-length cDNA clone encoding a murine alpha 1,2-mannosidase
      involved in the processing of mammalian Asn-linked oligosaccharides.
      Oligonucleotide primers were designed based on peptide sequences derived from the
      purified rabbit liver enzyme and were used to generate a 1011-base pair probe
      using the polymerase chain reaction. This probe was used to isolate clones from
      rabbit and mouse cDNA libraries. The full-length murine cDNA clone encodes a 655
      amino acid type II transmembrane protein with a 43-amino acid cytoplasmic tail, a
      single transmembrane domain, and a large COOH-terminal catalytic domain
      containing two potential N-glycosylation sites. Stable transfection of the murine
      alpha 1,2-mannosidase cDNA into mouse L cells resulted in a approximately 22-fold
      overexpression of alpha 1,2-mannosidase activity. Three transcripts were detected
      in rabbit tissues, whereas two were found in rat and mouse tissues. The sequences
      of the rabbit and mouse cDNA clones indicate that the multiple transcripts differ
      in the length of their 3' sequences as a result of the use of multiple
      polyadenylation signals. Immunolocalization detected cross-reactive material in a
      juxtanuclear pattern consistent with the Golgi complex. The catalytic portion of
      the murine alpha 1,2-mannosidase was found to bear a strong similarity to the
      processing alpha 1,2-mannosidase from Saccharomyces cerevisiae.

PMID- 8144581
TI  - The endothelial cell binding site for advanced glycation end products consists of
      a complex: an integral membrane protein and a lactoferrin-like polypeptide.
AB  - Advanced glycation end products (AGEs), formed as the result of the extended
      interaction of proteins with ketoses, modulate central properties of endothelial
      cells and mononuclear phagocytes by interacting with a cell surface binding site
      comprised of a novel integral membrane protein (receptor for AGE = RAGE) and a
      lactoferrin-like polypeptide (LF-L), the latter having sequence identity to
      lactoferrin (LF). To further understand this cellular binding site, the
      interaction of RAGE with LF-L and LF was characterized. By ligand blotting and a
      solid state competitive binding assay, 125I-LF-L and 125I-LF bound to RAGE
      immobilized on nitrocellulose membranes or polypropylene tubes in a time
      dependent and reversible manner, demonstrating a high affinity component with Kd
      approximately 100 pM. The interaction of 125I-LF-L and 125I-LF with RAGE was
      independent of iron in LF and was competed by addition of an excess of unlabeled
      carboxyl-terminal portion of LF. Cross-linking studies with purified 125I-LF-L
      and RAGE, in the presence of disuccinimidyl suberate, showed a new, slowly
      migrating band, corresponding to a complex of RAGE and LF-L, and cross-linking on
      mouse aortic endothelial cells showed two new slowly migrating bands on
      immunoblotting visualized with both anti-RAGE IgG and anti-LF-L IgG. These data
      lead us to propose that the endothelial cell surface binding site for AGEs
      consists of LF-L bound noncovalently to RAGE anchored in the cell membrane.

PMID- 8144582
TI  - Enhanced cellular oxidant stress by the interaction of advanced glycation end
      products with their receptors/binding proteins.
AB  - Attack by reactive oxygen intermediates, common to many kinds of cell/tissue
      injury, has been implicated in the development of diabetic and other vascular
      diseases. Such oxygen-free radicals can be generated by advanced glycation end
      products (AGEs), which are nonenzymatically glycated and oxidized proteins. Since
      cellular interactions of AGEs are mediated by specific cellular binding proteins,
      receptor for AGE (RAGE) and the lactoferrin-like polypeptide (LF-L), we tested
      the hypothesis that AGE ligands tethered to the complex of RAGE and LF-L could
      induce oxidant stress. AGE albumin or AGEs immunoisolated from diabetic plasma
      resulted in induction of endothelial cell (EC) oxidant stress, including the
      generation of thiobarbituric acid reactive substances (TBARS) and resulted in the
      activation of NF-kappa B, each of which was blocked by antibodies to AGE receptor
      polypeptides and by antioxidants. Infusion of AGE albumin into normal animals led
      to the appearance of malondialdehyde determinants in the vessel wall and
      increased TBARS in the tissues, activation of NF-kappa B, and induction of heme
      oxygenase mRNA. AGE-induced oxidant stress was inhibited by pretreatment of
      animals with either antibodies to the AGE receptor/binding proteins or
      antioxidants. These data indicate that interaction of AGEs with cellular targets,
      such as ECs, leads to oxidant stress resulting in changes in gene expression and
      other cellular properties, potentially contributing to the development of
      vascular lesions. Further studies will be required to dissect whether oxidant
      stress occurs on the cell surface or at an intracellular locus.

PMID- 8144583
TI  - Enhanced synthesis of tumor necrosis factor-inducible proteins, plasminogen
      activator inhibitor-2, manganese superoxide dismutase, and protein 28/5.6, is
      selectively triggered by the 55-kDa tumor necrosis factor receptor in human
      melanoma cells.
AB  - We have demonstrated that A375 melanoma cells express mRNA for both types of
      tumor necrosis factor (TNF) receptors and receptor proteins on their plasma
      membranes. Specific agonist and blocking antibodies to either 55-kDa (TNF-R1) or
      75-kDa (TNF-R2) TNF receptors combined with two-dimensional gel analysis were
      employed to determine which receptor type is responsible for mediating the
      induction of individual melanoma proteins. Our results indicate that the enhanced
      synthesis of proteins 21/>7 (M(r)/pI), 28/5.6, and 41/5.7 is selectively induced
      through TNF-R1. TNF induces these proteins; antagonist antibody to TNF-R1
      prevents their induction by TNF, and TNF-R1 agonist induces them in the absence
      of TNF. Identification of these proteins by immunoblot analysis proved that 21/>7
      is manganese superoxide dismutase, protein 28/5.6 is unrelated to 27/28-kDa heat
      shock protein, and protein 41/5.7 is plasminogen activator inhibitor-2.
      Furthermore, TNF cytotoxicity for A375 cells is also mediated by TNF-R1. These
      studies indicate that TNF-R1 is a critical signaling receptor for TNF action on
      A375 cells and demonstrate the potential use of TNF-R1 antibodies to selectively
      block or enhance specific effects of TNF on melanoma cells.

PMID- 8144584
TI  - Lysine methylation of mitochondrial ATP synthase subunit c stored in tissues of
      dogs with hereditary ceroid lipofuscinosis.
AB  - Certain forms of ceroid lipofuscinosis, a hereditary degenerative disease, are
      characterized by accumulation of large amounts of subunit c of mitochondrial ATP
      synthase in lysosomal storage bodies of numerous tissues. The subunit c protein
      appears to constitute a major fraction of the total storage body protein. In
      previous studies it was demonstrated that hydrolysates of total storage body
      protein from affected humans and sheep contain significant amounts of epsilon-N
      trimethyllysine (TML). This finding suggested that one or both of the two lysine
      residues of subunit c might be methylated in the stored form of the protein. The
      normal subunit c protein from mitochondria does not appear to be methylated.
      Using a putative canine model for the juvenile form of ceroid lipofuscinosis,
      analyses were conducted to determine whether lysosomal storage of subunit c was
      accompanied by lysine methylation of this protein. In affected dogs, as in humans
      and sheep with hereditary ceroid lipofuscinosis, the storage bodies were found to
      contain large amounts of subunit c protein, as indicated by polyacrylamide gel
      electrophoresis and partial amino acid sequence analysis. The subunit c protein
      partially purified from isolated storage bodies was found to contain lysine and
      TML in an almost equimolar ratio. Normal subunit c contains 2 lysine residues,
      one at position 7 and the other at position 43. Removal of the first 7 residues
      of the partially purified protein through sequential Edman degradation resulted
      in a dramatic increase in the TML to lysine ratio in the residual protein. This
      suggests that lysine residue 43 is methylated. Confirmation that residue 43 of
      the stored protein is TML was obtained by amino acid sequence analysis after
      cleavage of the protein with trypsin. This finding strongly suggests that
      specific methylation of lysine residue 43 of mitochondrial ATP synthase plays a
      central role in the lysosomal storage of this protein.

PMID- 8144585
TI  - Ca(2+)-dependent phosphorylation of myosin light chain kinase decreases the Ca2+
      sensitivity of light chain phosphorylation within smooth muscle cells.
AB  - Myosin light chain kinase (MLCK) is phosphorylated in contracting smooth muscle.
      The rate of phosphorylation of MLCK is slower than the rates of increase in
      cytosolic Ca2+ concentrations and phosphorylation of the regulatory light chain
      of myosin in intact tracheal smooth muscle cells in culture. In permeable cells,
      increasing the Ca2+ concentration increased the extent of myosin light chain and
      MLCK phosphorylation. The Ca2+ concentration required for half-maximal
      phosphorylation was 500 nM for MLCK and 250 nM for myosin light chain. Addition
      of KN-62 or a synthetic peptide CK II, inhibitors of multifunctional
      Ca2+/calmodulin-dependent protein kinase II activity, abolished MLCK
      phosphorylation. Under these conditions, the Ca2+ concentration required for half
      maximal light chain phosphorylation decreased to 170 nM. Thus, the Ca2+
      concentrations required for MLCK phosphorylation are greater than those required
      for light chain phosphorylation in smooth muscle cells. Furthermore,
      phosphorylation of MLCK decreases the Ca2+ sensitivity of light chain
      phosphorylation. These results can be explained by a regulatory scheme in which
      calmodulin available for myosin light chain kinase activation is limiting. This
      is supported by the retention of calmodulin when tracheal smooth muscle cells and
      tissues are permeabilized in relaxing solution and by the low mobility of
      rhodamine-calmodulin in intact tracheal smooth muscle cells.

PMID- 8144586
TI  - Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride
      analogues.
AB  - Diamine oxidase (histaminase), an enzyme that oxidatively deaminates putrescine
      and histamine, was purified from human placenta and from pig kidney. Both NH2
      terminal sequences are highly homologous to the human kidney amiloride-binding
      protein, previously thought to be a component of the amiloride-sensitive Na+
      channel. Monoclonal antibodies raised against the pig kidney amiloride-binding
      protein immunoprecipitate a polypeptide with the same M(r) (105,000) as that of
      pig kidney diamine oxidase. That polypeptide has both diamine oxidase activity
      and the capacity to bind [3H]phenamil, a tritiated amiloride derivative. Cells
      stably transfected with human kidney amiloride-binding protein cDNA express a
      high diamine oxidase activity. In transfected cells as well as with the purified
      enzyme, this activity was inhibited by amiloride and by some of its derivatives,
      such as phenamil and ethylpropylamiloride. Amiloride inhibition seems to be due
      to drug binding at the active site of the enzyme. These data indicate that human
      placental diamine oxidase is identical to the human kidney amiloride-binding
      protein and that amiloride analogues may have wider physiological effects besides
      those on epithelial ion transport.

PMID- 8144587
TI  - Primary structures for a mammalian cellular and serum copper amine oxidase.
AB  - The 6-hydroxydopa quinone-containing active site peptide from bovine serum amine
      oxidase has been found to be highly homologous to a segment of a cloned human
      kidney amiloride-binding protein (Barbry, P., Champe, M., Chassande, O.,
      Munemitsu, S., Champigny, G., Lingueglia, E., Maes, P., Frelin, C., Tartar, A.,
      Ullrich, A., and Lazdunski, M. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7347
      7351). Additionally, a second 38-residue tryptic peptide (peptide XI) isolated
      from bovine serum amine oxidase shows 82% identity with a portion near the
      carboxyl terminus of the human kidney amiloride-binding protein. When an extended
      active site peptide was isolated from porcine kidney diamine oxidase (Janes, S.
      M., Palcic, M. M., Scaman, C. H., Smith, A. J., Brown, D. E., Dooley, D. M.,
      Mure, M., and Klinman, J. P. (1992) Biochemistry 31, 12147-12154), it was found
      to be fully contained in the human kidney amiloride-binding protein. Examination
      of amiloride binding to bovine serum amine oxidase and porcine kidney diamine
      oxidase reveals dissociation constants of 196 and 9.1 microM, respectively. Taken
      together, these findings indicate that the cDNA isolated for human kidney
      amiloride-binding protein encodes a human kidney diamine oxidase. Two
      oligonucleotides, based on the tryptic peptide XI and active-site peptide of
      bovine serum amine oxidase, were used to amplify a portion of cDNA from a
      commercial bovine liver cDNA library through the use of the polymerase chain
      reaction. A full-length clone (2.7 kilobase pairs) for bovine serum amine oxidase
      was subsequently obtained through screening of the same cDNA library with the
      amplified 0.7-kilobase pair cDNA. These studies provide the first primary
      sequences for a mammalian cellular and serum copper amine oxidase. Computer
      alignment of amine oxidase cDNA-derived protein sequences reveals three conserved
      histidine residues, which are likely to be ligands to copper.

PMID- 8144588
TI  - Purification of the Xenopus laevis double-stranded RNA adenosine deaminase.
AB  - A double-stranded RNA adenosine deaminase that catalyzes the conversion of
      adenosines to inosines in duplex RNA substrates was purified to near homogeneity
      from Xenopus laevis eggs. The final specific activity was approximately 2.0 nmol
      of inosine min-1 mg-1 at 25 degrees C and pH 7.9 with a 794-base pair RNA
      substrate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a
      single major approximately 120-kDa protein band by silver staining. The purified
      enzyme migrated with an apparent molecular mass of 90 +/- 10 kDa during high
      performance liquid chromatography. Gel filtration of the partially purified
      enzyme gave an apparent molecular mass of 210 +/- 20 kDa, suggesting that the
      enzyme may dimerize or associate with other cellular components. Substrate
      modification was inhibited by excess substrate, thiol reagents, heparin, and
      moderate concentrations of monovalent cations.

PMID- 8144589
TI  - Murine cerebellar neurons express a novel gene encoding a protein related to cell
      cycle control and cell fate determination proteins.
AB  - We cloned cDNAs of a novel protein (designated V-1) that has been identified from
      among the developmentally regulated proteins in the rat cerebellum. Protein
      sequencing analysis (Taoka, M., Yamakuni, T., Song, S.-Y., Yamakawa, Y., Seta,
      K., Okuyama, T., and Isobe, T. (1992) Eur. J. Biochem. 207, 615-620) and cDNA
      sequence analysis revealed that the V-1 protein consists of 117 amino acids and
      contains 2.5 contiguous repeats of the cdc10/SWI6 motif, which was originally
      found in the products of the cell cycle control genes of yeasts and the cell fate
      determination genes in Drosophila and Caenorhabditis elegans. In situ
      hybridization histochemistry revealed that the expression of the V-1 gene is
      transiently increased in postmigratory granule cells during postnatal rat
      cerebellar development and thereafter is markedly suppressed, whereas Purkinje
      cells constitutively express V-1 mRNA. In contrast, cerebellar granule cells of
      the staggerer mutant mouse continue to express the V-1 gene even when the granule
      cells of the normal mouse have ceased to express the V-1 gene, suggesting that
      the expression of the V-1 gene in granule cells is regulated through the
      interaction with Purkinje cells. On the basis of these results, we postulate that
      the V-1 protein has a potential role in the differentiation of granule cells.

PMID- 8144590
TI  - cDNA sequence, gene structure, and in vitro expression of ace-1, the gene
      encoding acetylcholinesterase of class A in the nematode Caenorhabditis elegans.
AB  - Three genes, ace-1, ace-2, and ace-3, encode three acetylcholinesterase classes
      (A, B, and C) in the nematode Caenorhabditis elegans. A fragment of genomic DNA
      was amplified by a polymerase chain reaction (PCR) using degenerate
      oligonucleotides based on sequences conserved in the cholinesterase family. This
      fragment mapped to chromosome X at a position that perfectly matched the location
      of ace-1 previously determined by genetic methods. Comparison of genomic and cDNA
      sequences showed that the open reading frame was interrupted by eight introns.
      The product of ace-1 (ACE-1, 620 amino acids) presented 42% identity with Torpedo
      and human acetylcholinesterases, 41% with human butyrylcholinesterase, and 35%
      with Drosophila acetylcholinesterase. The overall structure of cholinesterases
      was conserved in ACE-1 as indicated by the conserved sequence positions of Ser
      216, His-468, and Glu-346 (S200, H440, E327 in Torpedo (AChE) as components of
      the catalytic triad, of the six cysteines which form three intrachain disulfide
      bonds, and of Trp-99(84), a critical side chain in the choline binding site.
      Spodoptera Sf9 cells were infected by a recombinant baculovirus containing ace-1
      cDNA. The secreted enzyme was active and existed as hydrophilic 5 and 11.5 S
      molecular forms. It hydrolyzed both acetylthiocholine and butyrylthiocholine and
      was inhibited by acetylthiocholine above 10 mM.

PMID- 8144591
TI  - Recombinant human betacellulin. Molecular structure, biological activities, and
      receptor interaction.
AB  - Soluble forms of human betacellulin (BTC) were purified to homogeneity from the
      conditioned medium of mouse A9 cells transfected with the BTC precursor cDNA.
      Three types of soluble BTC, designated BTC-1a, BTC-1b and BTC-2, were resolved by
      cation-exchange and size-exclusion column chromatography. Physicochemical
      analysis has revealed that BTC-1a represents the glycosylated, intact molecule
      composed of 80 amino acid residues (Asp32 to Tyr111 of the precursor molecule).
      BTC-1b appears to be a truncated molecule lacking 12 amino acid residues from the
      amino terminus of BTC-1a. BTC-2 was found to be a 50-amino acid molecule (Arg62
      to Tyr111) that corresponds to the epidermal growth factor (EGF) structural unit.
      The biological activities of these BTC molecules were essentially identical as
      judged by their mitogenicity on Balb/c 3T3 fibroblasts. BTC and EGF were
      equipotent in stimulating Balb/c 3T3 cell proliferation and rat mesangial cell
      Ca2+ mobilization as well as in inhibiting the growth of human epidermoid
      carcinoma A431 cells. BTC and EGF antagonized each other with similar dose
      dependence for binding to A431 cells, indicating that these factors bind the same
      receptor molecules with equivalent avidity. The Kd value of EGF receptor (EGFR)
      and BTC is 0.5 nM as determined on Balb/c 3T3 cells. In addition, human mammary
      carcinoma MDA-MB-453 cells, which express multiple members of the EGFR family,
      were found to possess 2.7 x 10(3) BTC binding sites/cell, and the binding was
      readily quenched by EGF. These results suggest that the primary receptor for BTC
      is EGFR.

PMID- 8144592
TI  - The HBP-1 family of wheat basic/leucine zipper proteins interacts with
      overlapping cis-acting hexamer motifs of plant histone genes.
AB  - The type I element (CCACGTCANCGATCCGCG) is a cis-acting element that is essential
      for the transcriptional regulation of the wheat histone H3 (TH012) gene. The
      sequence CCACGTCA in the type I element resembles various plant regulatory
      elements that share an ACGT core sequence, which can be recognized by different
      basic/leucine zipper (bZIP) proteins. Here we describe the isolation and
      characterization of wheat cDNA clones encoding three novel bZIP proteins,
      designated HBP (histone promoter-binding protein)-1a(1), HBP-1a(c14), and HBP
      1b(c1). These proteins specifically bind to the ACGT core sequence and, together
      with previously identified HBP-1a(17) and HBP-1b(c38), constitute a protein
      family, named the HBP-1 family. Based on their structural characteristics and DNA
      binding specificities, members of the HBP-1 family can be grouped into HBP-1a and
      HBP-1b subfamilies. The HBP-1a isoforms are characterized by their N-terminal
      proline-rich domain and a C-terminal bZIP domain, which binds to the CCACGT
      motif. In contrast, the HBP-1b isoforms have a bZIP domain at the N terminus,
      which binds to the ACGTCA motif, and a glutamine-rich domain at the C terminus.
      All members of both subfamilies interact with the CCACGTCA sequence, but their
      DNA binding specificities and affinities differ. Since HBP-1a isoforms form
      heterodimers in all pairwise combinations, heterodimer formation among these bZIP
      proteins may generate an expanded repertoire of regulatory potential for gene
      expression in plants.

PMID- 8144593
TI  - Role of histidine 35 of the S1 subunit of pertussis toxin in the ADP-ribosylation
      of transducin.
AB  - Molecular modeling of the S1 subunit (S1) of pertussis toxin with other ADP
      ribosylating bacterial exotoxins predicted that histidine 35 (His-35) would
      residue within the active site of S1. Recombinant derivatives of S1 (rS1 and the
      C180 peptide) which contained either a H35Q or H35P mutation were analyzed to
      determine the role of His-35 in ADP-ribosylation. C180 peptide is a recombinant
      peptide composed of the amino-terminal 180 amino acids of S1. Under linear
      velocity conditions, C180H35Q possessed 2% of wild type C180 peptide activity and
      C180H35P possessed no detectable activity in the ADP-ribosylation of transducin.
      The H35Q mutation did not change the affinity of recombinant peptides for NAD or
      two targets for ADP-ribosylation, transducin, or alpha i3C20, but did lower the
      kcat in the NAD glycohydrolase and ADP-ribosyltransferase reactions. Neither the
      H35Q nor H35P mutation reduced the ability of recombinant proteins to be
      photocross-linked with NAD which was consistent with the His-35 mutations not
      reducing the affinity for NAD. These data indicate that His-35 does not reduce
      the affinity of S1 for NAD or transducin, but functions as a catalytic residue in
      the ADP-ribosylation reaction possibly in a hydrogen bonding capacity.

PMID- 8144594
TI  - Sorting of membrane proteins in the yeast secretory pathway.

PMID- 8144595
TI  - Differences between lumen targeting domains of chloroplast transit peptides
      determine pathway specificity for thylakoid transport.
AB  - Nuclear encoded thylakoid lumen proteins are imported into the chloroplast storma
      and further directed across thylakoid membranes by lumen targeting domains.
      Recently, we showed that there are two protein-specific pathways for transport
      into the lumen. This was unexpected in that lumen targeting domains have similar
      properties, all containing bacterial signal peptide motifs. Nevertheless,
      sequence homology analysis suggests that pathway specificity is determined by
      elements in the lumen targeting domain. To test this, we constructed and analyzed
      chimeric proteins in which transit peptides from proteins transported by one
      pathway were fused to the mature domains of proteins directed by the other. We
      also investigated the transport characteristics of a previously unexamined
      protein whose pathway was predicted by sequence similarity analysis. Our results
      confirm that lumen targeting domains contain pathway sorting elements and further
      indicate that distinct energy and stroma requirements for transport are pathway
      characteristics, unrelated to the passenger protein. These findings suggest the
      operation of two mechanistically different translocators.

PMID- 8144596
TI  - A conditionally lethal yeast mutant blocked at the first step in glycosyl
      phosphatidylinositol anchor synthesis.
AB  - Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of
      eukaryotic cells and may also serve as sorting signals on proteins and
      participate in signal transduction. We have isolated a Saccharomyces cerevisiae
      GPI anchoring mutant, gpi1, using a colony screen for cells blocked in
      [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in
      the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first
      intermediate in GPI synthesis, and is also temperature-sensitive for growth.
      Completion of the first step in GPI assembly is therefore required for growth of
      the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be
      exploited as a target for antifungal or antiparasitic agents.

PMID- 8144597
TI  - Macrophages adhere to glucose-modified basement membrane collagen IV via their
      scavenger receptors.
AB  - Scavenger receptors have been reported to mediate macrophage adhesion to serum
      coated plastic surfaces. We report here that scavenger receptors promote the
      divalent cation independent adhesion of human monocytes and macrophages to
      surfaces coated with non-enzymatically glycated collagen IV but not to surfaces
      coated with native collagen IV. Ligands for scavenger receptor types I and II
      blocked adhesion of monocytes and macrophages to non-enzymatically glycated
      collagen IV but had no effect on adhesion of these cells to albumin-coated
      surfaces. U937 human promonocyte-like cells transfected with cDNA encoding bovine
      scavenger receptor I or II adhered to surfaces coated with glycated-collagen IV
      but not to surfaces coated with native collagen IV. A synthetic peptide
      homologous to the domain of bovine scavenger receptor that binds modified low
      density lipoproteins (residues 327-343) inhibited the adhesion of U937 cells
      transfected with cDNA encoding bovine scavenger receptor II to glycated collagen
      IV, whereas a control peptide from the alpha helical domain of scavenger receptor
      II (residues 121-137) had no effect on adhesion of these cells. Macrophages
      plated on surfaces coated with glycated collagen IV were unable to endocytose
      acetylated low density lipoproteins from the medium, suggesting that their
      scavenger receptors were occupied in binding these cells to the substrate. These
      findings suggest new roles for scavenger receptors in the accelerated development
      of vascular lesions observed in diabetics.

PMID- 8144598
TI  - Racemization of Asp23 residue affects the aggregation properties of Alzheimer
      amyloid beta protein analogues.
AB  - The beta proteins in amyloid deposits of Alzheimer's disease have been found to
      be racemized and/or isomerized at their Asp residues (Roher, A. E., Lowenson, J.
      D., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zurcher
      Neely, H. A., Heinrikson, R. L., Ball, M. J., and Greenberg, B. D. (1993) J.
      Biol. Chem. 268, 3072-3083). To elucidate the effect of racemization on the
      aggregation properties of beta proteins, we synthesized four beta protein
      analogues in which D-Asp was substituted for L-Asp residues, i.e. normal beta 1
      35, [D-Asp7]beta 1-35, [D-Asp23]beta 1-35, and [D-Asp7,D-Asp23]beta 1-35. The
      aggregation and fibril formation of the peptides were examined by means of
      spectrophotometry, sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS
      PAGE), and electron microscopy. Of the four peptides, [D-Asp23]beta 1-35 showed
      the earliest increase in turbidity and appearance of a smear in SDS-PAGE. This
      was followed by [D-Asp7,D-Asp23]beta 1-35 and normal beta 1-35. [D-Asp7]beta 1-35
      was considerably delayed in showing these signs of aggregation. Corresponding
      with the increase in turbidity and the appearance of a smear in SDS-PAGE, fibril
      formation was observed in electron microscopy. These results reveal that the
      aggregation properties of beta 1-35 peptides are affected by racemization of
      their Asp residues depending on their position. Racemization at amino acid
      position 23 accelerated the peptide aggregation and fibril formation, while that
      at position 7 slowed down this reaction. This suggests that the site-specific
      racemization of beta protein may be involved in the amyloid fibril formation in
      Alzheimer's disease.

PMID- 8144599
TI  - Phospholipid-stimulated autophosphorylation activates the G protein-coupled
      receptor kinase GRK5.
AB  - G protein-coupled receptor kinases (GRKs) play an important role in mediating
      agonist-specific desensitization of numerous G protein-coupled receptors. GRK5, a
      recently identified member of the GRK family, undergoes a rapid phospholipid
      stimulated autophosphorylation to a stoichiometry of approximately 2 mol of
      phosphate/mol of GRK5. The ability of phospholipids to stimulate
      autophosphorylation is largely blocked by a glutathione S-transferase fusion
      protein containing the last 102 amino acids of GRK5 (amino acids 489-590),
      suggesting that this is a primary region involved in GRK5/phospholipid
      interaction. Phosphoamino acid determination and mutagenesis studies demonstrate
      that autophosphorylation of GRK5 occurs primarily at residues Ser-484 and Thr
      485. Expression and characterization of a mutant GRK5 that does not
      autophosphorylate (S484A and T485A) reveals that the mutant has a approximately
      15-20-fold reduced ability to phosphorylate the beta 2-adrenergic receptor and
      rhodopsin compared to wild type GRK5. These results suggest that phospholipid
      stimulated autophosphorylation may represent a novel mechanism for membrane
      association and regulation of GRK5 activity.

PMID- 8144600
TI  - Respective roles of glucose, fructose, and insulin in the regulation of the liver
      specific pyruvate kinase gene promoter.
AB  - The L-type pyruvate kinase (L-PK) is a key enzyme of the glycolytic pathway
      mainly expressed in the liver. Rat liver contains a regulatory protein that
      inhibits glucokinase (GK) activity. The effect of this protein is greatly
      reinforced by the fructose 6-phosphate and antagonized by the fructose 1
      phosphate (Van Schaftingen, E. (1989) Eur. J. Biochem. 179, 179-184). In
      hepatocytes, fructose in low concentrations is phosphorylated into fructose 1
      phosphate, and therefore is able to active GK in the absence of insulin via the
      regulatory protein in the liver. In primary culture of rat hepatocytes, 0.2 mM
      fructose in the presence of 20 or 40 mM glucose stimulated the activity of the L
      PK gene promoter fused with the chloramphenicol acetyltransferase reporter gene,
      regardless of the addition of insulin, through the glucose/insulin response
      element. A constitutive GK expression vector co-transfected with the L
      PK/chloramphenicol acetyltransferase construct is also able to confer an insulin
      independent glucose responsiveness in hepatocytes. Thus, the insulin effect on
      glucose-dependent activation of the L-PK promoter is, under these experimental
      conditions, to permit glucose phosphorylation through the stimulation of the GK
      synthesis. In the presence of glucose, the L-PK promoter can also be activated by
      a post-translational GK activation, mediated by a low concentration of fructose
      acting via the regulatory protein of glucokinase.

PMID- 8144601
TI  - Binding of G protein beta gamma-subunits to pleckstrin homology domains.
AB  - Ligand-induced activation of many receptors leads to dissociation of the alpha-
      and beta gamma-subunit complexes of heterotrimeric G proteins, both of which
      regulate a variety of effector molecules involved in cellular signaling
      processes. In one case, a cytosolic enzyme, the beta-adrenergic receptor kinase
      (beta ARK) binds to the dissociated, prenylated, membrane-anchored beta gamma
      subunits of heterotrimeric G proteins (G beta gamma) and is thereby targeted to
      its membrane-bound receptor substrate. Quite recently, numerous proteins involved
      in cellular signal transduction have been shown to contain sequences homologous
      with a "domain" originally identified in the protein "pleckstrin" (pleckstrin
      homology domain; PH domain) and subsequently found in the G beta gamma
      interaction region of the beta ARK sequence. Here we demonstrate that glutathione
      S-transferase-fusion proteins, containing sequences encompassing the PH domain of
      nine proteins from this group, bind G beta gamma to varying extents. Binding of G
      beta gamma to these fusion proteins was documented either by a direct binding
      assay or by ability to block G beta gamma-mediated membrane translocation of beta
      ARK1. G beta gamma binding to these fusion proteins was inhibited by the alpha
      subunit of Go (Go alpha), indicating that the binding of G beta gamma to G alpha
      and the PH domain-containing fusion proteins is mutually exclusive. Studies with
      a series of truncated PH domains derived from the Ras-guanine-nucleotide
      releasing factor indicate that the G beta gamma binding domain includes only the
      C-terminal portion of the PH domain and sequences just distal to this. Protein
      protein interactions between G beta gamma and PH domain-containing proteins may
      play a significant role in cellular signaling analogous to that previously
      demonstrated for Src homology 2 and 3 domains.

PMID- 8144602
TI  - DNA polymerase alpha overcomes an error-prone pause site in the presence of
      replication protein-A.
AB  - Eukaryotic DNA polymerase alpha pauses at some sites on the natural DNA template
      of M13mp2. Terminal misincorporations of dA or dG, in place of dT, by DNA
      polymerase alpha have been reported to be within one of the pause sites, pause
      site II (positions 6269 and 6270 (Fry, M., and Loeb, L.A. (1992) Proc. Natl.
      Acad. Sci. U.S.A. 89, 763-767)). The DNA products arrested within pause site II
      (position 6270) were separated, annealed with synthetic templates, and further
      elongated by DNA polymerase alpha. It was confirmed that a considerable amount of
      terminal misincorporation of dG in place of dT occurred at this position. When
      M13mp2 DNA was coated with various amounts of replication protein-A (RP-A),
      however, DNA polymerase alpha was able to overcome the pause site II, whereas
      pause bands at other sites barely decreased. In contrast, Escherichia coli single
      stranded DNA-binding protein did not specifically abolish the arrested band at
      pause site II, though it generally suppressed the reaction. Since RP-A hardly
      increased the elongation frequency from the primer carrying a 3'-mismatched
      terminal deoxynucleotide, the reduction of arrested products by RP-A may be
      attributed to the change in the incorporation mode from noncomplementary to
      complementary deoxynucleotides within pause site II and may not be due to the
      reinitiation from the mismatched 3'-terminal deoxynucleotide. To confirm this, we
      amplified the reaction products at pause site III by means of a polymerase chain
      reaction method and showed that the complementary strand to pause site II, which
      was elongated in the presence of RP-A, did not carry any detectable misinsertion.
      Therefore, the errorprone step of the DNA synthesis catalyzed by DNA polymerase
      alpha may be readily avoided by RP-A.

PMID- 8144603
TI  - Evidence for the involvement of Rab3A in Ca(2+)-dependent exocytosis from adrenal
      chromaffin cells.
AB  - Bovine chromaffin cells are nondividing primary secretory cells that store and
      secrete catecholamine and a variety of proteins including chromogranins, opiate
      peptides, and opiate precursors. A transient transfection technique based upon
      the expression of human growth hormone as a reporter for the regulated secretory
      pathway was used to study the role of a Ras-like, GTP-binding protein, Rab3a, in
      Ca(2+)-dependent exocytosis. Immunocytochemistry and flow cytometry revealed that
      growth hormone and Rab proteins were coexpressed in the same cells.
      Overexpression of the wild type protein and expression of a mutant protein
      Rab3aQ81L both inhibited nicotinic agonist-stimulated exocytosis in intact cells.
      Expression of Rab3aQ81L also inhibited Ca(2+)-dependent secretion from
      permeabilized cells. Two other mutants, Rab3aN135I and Rab3aT36N, which
      correspond to dominant acting mutants of Ras, caused limited and no inhibition,
      respectively, of agonist-stimulated exocytosis. These data provide direct
      evidence that Rab3a plays an important role in Ca(2+)-triggered exocytosis. We
      suggest that Rab3a is an inhibitor of secretion, perhaps as part of a pre-fusion
      complex with secretory vesicles. Elevated Ca2+ may trigger exocytosis by
      overcoming the inhibition by Rab3a.

PMID- 8144604
TI  - Protein kinase A phosphorylation and G protein regulation of purified renal Na+
      channels in planar bilayer membranes.
AB  - Purified bovine renal epithelial Na+ channels incorporated into planar lipid
      bilayer membranes were used to evaluate the biophysical consequences of its
      phosphorylation by protein kinase A (PKA). We also studied the effects of
      pertussis toxin-induced ADP-ribosylation on single channel activity of
      nonphosphorylated and PKA-phosphorylated channels. PKA-induced phosphorylation
      resulted in a significant increase in single channel open probability (Po) with
      no change in single channel conductance, as well as increased the probability of
      multiple channel openings in the bilayer. Further, PKA conferred a voltage
      sensitivity to channel gating without affecting open channel conduction
      properties. PKA-phosphorylated Na+ channels were inhibited by subsequent ADP
      ribosylation with pertussis toxin (PTX). Addition of guanosine 5'-3-O
      (thio)triphosphate reversed this inhibition. However, exposure of
      nonphosphorylated Na+ channels to PTX increased channel open probability by a
      factor of 3-5. These results demonstrate that a cAMP-dependent pathway is an
      important regulatory element for amiloride-sensitive Na+ channels and that the
      effects of PTX-induced ADP-ribosylation of the channel-associated Gi protein on
      function depend upon the previous phosphorylation state of the protein.

PMID- 8144605
TI  - The H(+)-ATPase from reticulocyte endosomes reconstituted into liposomes acts as
      an iron transporter.
AB  - The H(+)-ATPase from reticulocyte endosomes was purified and reconstituted into
      liposomes, and protein-dependent iron transport was observed. Reconstitution of
      the H(+)-ATPase into liposomes was performed by sonicating a lipid mixture, with
      a composition similar to the reticulocyte plasma membrane, in a buffer containing
      ferric citrate. The nonencapsulated iron:citrate was removed by gel filtration
      and the proteoliposomes diluted into 1 mM FerroZine. Upon addition of ascorbate,
      an initial efflux of 2.9 +/- 0.3 x 10(-2) mumol of iron/mg of ATPase/min and 56
      +/-7% of total internal Fe(II) was detected by formation of the Fe(II)-FerroZine
      complex with an absorbance at 562 nm or radioactivity of 59Fe(II)-FerroZine
      following separation using gel filtration. Both thiosulfate and ferrocyanide
      could substitute for ascorbate. Citrate or EGTA could substitute for FerroZine.
      The initial rate of Fe(II) efflux was decreased by 41 or 17% using 100 microM of
      the cation channel inhibitor N,N'-dicyclohexylcarbodiimide or 70 microM of the
      ATP hydrolysis inhibitor N-ethylmaleimide, respectively, but was unaffected by
      the presence of ATP. The amount of iron transported was decreased 51 or 39% by
      100 microM N,N'-dicyclohexylcarbodiimide or 70 microM of the ATPase inhibitor 7
      chloro-4-nitrobenz-2-oxa-1,3-diazole. The amount of Fe(III) transport was 80%
      lower than Fe(II) when reductants were not present internally or externally
      although the apparent rate constants were identical when ascorbate was externally
      present. These results suggest that this vacuolar H(+)-ATPase may transport iron.

PMID- 8144606
TI  - Characterization of an acetylcholine receptor alpha 3 gene promoter and its
      activation by the POU domain factor SCIP/Tst-1.
AB  - Genes encoding neuronal nicotinic acetylcholine receptors exhibit restricted
      patterns of expression in the nervous system. We are interested in elucidating
      the molecular mechanisms responsible for establishing these patterns of
      expression. This paper presents the characterization of regulatory elements
      upstream of the neuronal nicotinic acetylcholine receptor alpha 3 gene. We have
      identified a GC-rich multistart site promoter adjacent to the alpha 3 coding
      region. Similar alpha 3 start sites were identified in PC12 cells and sympathetic
      ganglion neurons, suggesting similar control mechanisms in the clonal line and
      peripheral neurons. The start site region lacks TATA-like sequences but does
      contain initiator-like sequences. We show, in transient transfection assays, that
      the POU domain transcription factor, SCIP/Tst-1, specifically activates alpha 3
      in a neural context. Other POU domain factors tested only weakly activated or
      repressed alpha 3. Unexpectedly, we found that alpha 3 basal activity and
      SCIP/Tst-1 activation of alpha 3 is not dependent on the SCIP/Tst-1 binding sites
      found upstream of the gene. In addition, mutations in the SCIP/Tst-1 coding
      region that prevent the factor from binding to DNA with high affinity do not
      obliterate alpha 3 activation. These results lead us to propose that alpha 3
      activation by SCIP/Tst-1 is achieved via protein-protein interactions between
      SCIP/Tst-1 and a specific complement of transcription factors that act directly
      on the promoter.

PMID- 8144607
TI  - The alpha/beta subunit interaction in H(+)-ATPase (ATP synthase). An Escherichia
      coli alpha subunit mutation (Arg-alpha 296-->Cys) restores coupling efficiency to
      the deleterious beta subunit mutant (Ser-beta 174-->Phe).
AB  - The Ser-beta 174 residue of the Escherichia coli H(+)-ATPase beta subunit has
      been shown to be near the catalytic site together with Gly-beta 149, Gly-beta
      172, Glu-beta 192, and Val-beta 198 (Iwamoto, A., Park, M.-Y., Maeda, M., and
      Futai, M. (1993) J. Biol. Chem. 268, 3156-3160). In this study, we introduced
      various residues at position 174 and found that the larger the side chain volume
      of the residue introduced, the lower the enzyme activity became. The Phe-beta 174
      mutant was defective in energy coupling between catalysis and transport, whereas
      the Leu-beta 174 mutant could couple efficiently, although both mutants had
      essentially the same ATPase activities (approximately 10% of the wild type). The
      defective energy coupling of the Phe-beta 174 mutant was suppressed by the second
      mutation (Arg-alpha 296-->Cys) in the alpha subunit. The Cys-alpha 296/Phe-beta
      174 mutant had essentially the same membrane ATPase activity as the Phe-beta 174
      single mutant when assayed under the conditions that stabilize the double mutant
      enzyme. These results indicate the importance of the alpha/beta interaction,
      especially that between the regions near Arg-alpha 296 and Ser-beta 174, for
      energy coupling in the H(+)-ATPase. The 2 residues (Ser-beta 174 and Arg-alpha
      296) may be located nearby at the interface of the two subunits. About 1 mol of N
      [14C]ethylmaleimide could bind to 1 mol of the alpha subunit of Cys-alpha 296/Phe
      beta 174 or Cys-alpha 296 mutant ATPase, but could not inhibit the enzyme
      activity. This is the first intersubunit mutation/suppression approach to ATPase
      catalysis and its energy coupling.

PMID- 8144608
TI  - Staurosporine induces the cell surface expression of both forms of human tumor
      necrosis factor receptors on myeloid and epithelial cells and modulates ligand
      induced cellular response.
AB  - Staurosporine, an inhibitor of protein kinase C, is commonly used to inhibit the
      growth factor-induced signal transduction pathway at the post-receptor level. In
      this report, we examined the effect of staurosporine on the constitutive
      expression of tumor necrosis factor (TNF) receptors in K562, a human
      erythroblastoid leukemic cell line. Exposure of these cells to staurosporine
      enhanced cell surface expression of TNF receptors by almost 7-fold in a dose- and
      time-dependent fashion. Maximum induction occurred at a concentration of 20 nM of
      the agent for 16 h at 37 degrees C. Induction of the TNF receptor was found to be
      temperature-dependent. No induction was observed at 22 or at 4 degrees C,
      suggesting the role of cell metabolism. Scatchard analysis indicated an increase
      in receptor number without any change in receptor affinity. TNF receptors were
      induced by staurosporine on a wide variety of human cells of both epithelial
      (primarily p60 receptors) and myeloid (mainly p80 receptor) origin. Receptor
      specific antibodies showed that both TNF receptors were induced. The induction
      was abolished by inhibitors of protein synthesis, thus suggesting the de novo
      synthesis of the receptor. Furthermore, we found that staurosporine had no effect
      on the internalization or shedding of the receptor, but it induced the mRNA for
      both forms of the TNF receptor. Inhibitors of tyrosine kinases had no effect on
      the induction of TNF receptors. Modulation of the receptor number by
      staurosporine correlated with the enhancement of antiproliferative effects of TNF
      against different tumor cells. Thus, overall these results indicate that protein
      kinase C may be involved in the signal transduction of TNF not only at the
      postreceptor level but also at the receptor level.

PMID- 8144609
TI  - Luminal communication between intracellular calcium stores modulated by GTP and
      the cytoskeleton.
AB  - The activation properties of inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+
      stores in permeabilized and intact hepatocytes were investigated by monitoring
      Mn2+ quench of fura-2 compartmentalized within these stores, as Mn2+ passed
      through InsP3-activated channels in a retrograde manner. In cells permeabilized
      in suspension the InsP3-sensitive pool size was dependent on InsP3 dose, and
      there was a large unresponsive compartment. By contrast, essentially all of the
      compartmentalized dye was accessible following activation of a small fraction of
      the InsP3 receptors in carefully permeabilized attached cells. After loading the
      cytosol of intact hepatocytes with Mn2+, both submaximal and maximal vasopressin
      doses caused complete quench of the entire intracellular pool of
      compartmentalized fura-2. Vasopressin-induced Mn2+ quench occurred in a stepwise
      manner at doses that gave cytosolic Ca2+ oscillations, reflecting periodic
      opening of intracellular Ca2+ channels. Pretreatment with thapsigargin to
      eliminate feedback effects of Ca2+ fluxes converted the steps to a continuous
      quench. The data suggest that Ca2+ stores in attached permeabilized and intact
      hepatocytes are luminally connected, making the entire store accessible to InsP3.
      In cells permeabilized in suspension, GTP increased InsP3-sensitive pool size,
      and this effect was inhibited by cytochalasin B. GTP did not change the initial
      rate of Mn2+ quench but increased the proportion of slowly accessible stores in
      the InsP3-sensitive compartment, apparently by recruitment of InsP3-insensitive
      stores. Preincubation on ice or with cytoskeletal inhibitors dissociated slowly
      accessible compartments from the InsP3-sensitive stores in both intact and
      subsequently permeabilized attached hepatocytes. Addition of GTP to permeabilized
      cells reversed this disruption of store continuity. It is suggested that GTP- and
      cytoskeleton-dependent luminal communication between Ca2+ stores is an important
      determinant of function, which could modulate the availability of Ca2+ for
      release.

PMID- 8144610
TI  - The influence of apolipoproteins on the structure and function of spheroidal,
      reconstituted high density lipoproteins.
AB  - This study investigates the influence of apolipoproteins on the structure and
      function of spheroidal, reconstituted high density lipoproteins (rHDL).
      Spheroidal rHDL containing apolipoprotein (apo) A-I, (A-I)rHDL, were prepared by
      incubating discoidal rHDL with low density lipoproteins and lecithin:cholesterol
      acyltransferase. Spheroidal rHDL containing apoA-II, (A-II)rHDL, were prepared by
      displacing apoA-I from (A-I)rHDL with apoA-II. When the (A-I)rHDL were subjected
      to agarose gel electrophoresis, their migration was retarded relative to native
      HDL. The (A-II)rHDL migrated slower than either the (A-I)rHDL or native HDL.
      Spectroscopic studies showed that the packing order of the rHDL phospholipids was
      independent of apolipoprotein composition and that the polarity, or hydration, of
      the lipid-water interface of the (A-I)rHDL was greater than that of the (A
      II)rHDL. When the rHDL were incubated with very low density lipoproteins (VLDL)
      and cholesteryl ester transfer protein, comparable amounts of cholesteryl ester
      (CE) were transferred from (A-I)rHDL and (A-II)rHDL to VLDL. The transfer of
      triglyceride (TG) from VLDL to (A-I)rHDL and (A-II)rHDL was also comparable.
      Similar results were obtained when Intralipid was substituted for VLDL. It is
      concluded that (i) apolipoproteins influence the surface charge of spheroidal
      rHDL, (ii) the hydration of the lipid-water interface of (A-I)rHDL is greater
      than that of (A-II)rHDL and (ii) cholesteryl ester transfer protein-mediated
      transfers of CE and TG between spheroidal rHDL and TG-rich particles are
      independent of rHDL apolipoprotein composition.

PMID- 8144611
TI  - Regulation of phosphoprotein p18 in leukemic cells. Cell cycle regulated
      phosphorylation by p34cdc2 kinase.
AB  - p18 is a phosphoprotein that is expressed at very high levels in leukemic cells,
      at moderately high levels in proliferating normal lymphocytes, and at low levels
      in quiescent lymphocytes. Induction of terminal differentiation of leukemic cells
      in culture results in a decrease in cellular proliferation. These phenotypic
      changes are associated with rapid phosphorylation of p18, followed by a more
      gradual decrease in the level of its mRNA expression. More than 12 different
      phosphorylation products of p18 have been identified in different cells by high
      resolution two-dimensional polyacrylamide gel electrophoresis. Previous studies
      have suggested that p18 may be a substrate for protein kinase C in some cellular
      processes and protein kinase A in others. In this report, we show that the
      phosphorylation of p18 increases as cells progress toward the G2-M phases of the
      cell cycle in proliferating leukemic cells. We have examined the hypothesis that
      the putative role of p18 in cellular proliferation may be mediated by its
      involvement in the p34cdc2 kinase signal transduction pathway. We have produced
      recombinant p18 in bacterial cells and shown that it can be phosphorylated in
      vitro by purified p34cdc2 kinase with a stoichiometry of 0.86 mol of PO4/mol of
      substrate. We have used site-directed mutagenesis to demonstrate that the site of
      p34cdc2 phosphorylation is the serine at position 38. This same site has
      previously been shown to be phosphorylated in vivo in bovine brain along with
      another serine at position 25. The observation that p18 gets phosphorylated in
      the G2-M phases of the cell cycle and the demonstration that p18 is
      phosphorylated efficiently by p34cdc2 kinase in vitro at a residue that is also
      phosphorylated in vivo support the hypothesis that p18 may be a physiologic
      substrate for p34cdc2 kinase in vivo. We have also examined the effect of
      inhibiting the expression of p18 on cell cycle progression. These experiments
      demonstrated that antisense inhibition of the expression of p18 in K562
      erythroleukemia cells is associated with a decrease in cellular proliferation and
      accumulation of cells in the G2-M phases of the cycle. The implications of these
      findings to the proposed role of p18 in the regulation of cellular proliferation
      are discussed.

PMID- 8144612
TI  - Lipoprotein lipase domain function.
AB  - Human lipoprotein lipase (LPL) monomer consists of two domains, a larger NH2
      terminal domain that contains catalytic residues and a smaller COOH-terminal
      domain that modulates substrate specificity and is a major determinant of heparin
      binding. Analyses of NH2-terminal domain function were performed after site
      directed mutagenesis of the putative active-site serine residue, while COOH
      terminal domain function was assessed following reaction with a monoclonal
      antibody. The native enzyme and mutant LPL in which serine 132 was replaced with
      alanine, cysteine, or glycine were transiently expressed in COS-7 cells. Mutant
      proteins were synthesized and secreted at levels comparable to native LPL;
      however, none of the mutants retained enzymatic activity. The mutant with alanine
      replacing serine 132 was purified and shown to be inactive with both esterase and
      lipase substrates; however, binding to a 1,2-didodecanoyl-sn-glycero-3
      phosphatidylcholine monolayer was comparable to native LPL. These results are
      consistent with a catalytic, and not a lipid binding, role for serine 132. To
      investigate the function of the smaller COOH-terminal domain, LPL lipolytic and
      esterolytic activities as well as heparin binding properties were determined
      after reaction with a monoclonal antibody specific for this domain. Lipolytic
      activity was inhibited by the monoclonal antibody, whereas esterolytic activity
      was only marginally affected, indicating that the LPL COOH-terminal domain is
      required for lipolysis, perhaps by promoting interaction with insoluble
      substrates. Also, the affinity of antibody-reacted LPL for heparin was not
      significantly different from that of LPL alone, suggesting that (i) the heparin
      binding site is physically distinct from the COOH-terminal domain region required
      for lipolysis and (ii) binding of antibody did not cause dimer dissociation. A
      model is proposed for the two LPL domains fulfilling different roles in the
      lipolytic process.

PMID- 8144613
TI  - Interaction of desacetamidocolchicine, a fast binding analogue of colchicine with
      isotypically pure tubulin dimers alpha beta II, alpha beta III, and alpha beta
      IV.
AB  - Desacetamidocolchicine (DAAC) is a colchicine analogue that lacks the acetamido
      side chain in the ring-B of colchicine. Unlike colchicine, it binds to tubulin
      very quickly, and yet it has powerful antimitotic properties. It has been
      demonstrated that the beta-tubulin isoforms differ significantly in their
      interactions with colchicine. In an effort to understand the role of the ring-B
      of colchicine, we have studied the interaction of DAAC with purified beta-tubulin
      isoforms. The association was studied fluorometrically using a stopped-flow
      instrument under pseudo-first-order conditions in the presence of a large excess
      of drug. The observed pseudo-first-order rate constants increased in a nonlinear
      way with the drug concentration, indicating that the binding of DAAC to tubulin
      isoforms occur in two steps as is true for the binding of colchicine to tubulin
      (Garland, D.L. (1978) Biochemistry 17, 4266-4272), [formula: see text] where the
      first step is a fast reversible binding and the second step is a slow
      conformational change leading to the formation of the stable complex (T.DAAC)*.
      Kinetic analysis shows that the tubulin isoforms exhibit very little differences
      in their K1 values, which are 5794 +/- 670, 7109 +/- 1800, and 8993 +/- 1780 M-1
      for alpha beta II, alpha beta III, and alpha beta IV, respectively. The k2 values
      for alpha beta II, alpha beta III, and alpha beta IV are 0.67 +/- 0.05, 0.05 +/-
      0.006, and 0.59 +/- 0.07 s-1, respectively. The apparent on-rate constants
      (k(on,app) = K1k2) for alpha beta II, alpha beta III, and alpha beta IV are 3907
      +/- 530, 376 +/- 80, and 5305 +/- 1200 M-1 s-1, respectively. The off-rate
      constants as measured by the loss of fluorescence of drug-tubulin complexes in
      the presence of a large excess of podophyllotoxin are 6.3 x 10(-4), 5.2 x 10(-4),
      and 5.7 x 10(-4) s-1, respectively, for alpha beta II, alpha beta III, and alpha
      beta IV. The affinity constants as determined by Scatchard analyses are 2.5 x
      10(6), 1.5 x 10(6), and 4 x 10(6) M-1 for alpha beta II, alpha beta III, and
      alpha beta IV, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8144614
TI  - Developmental expression of trout egg polysialoglycoproteins and the prerequisite
      alpha 2,6-, and alpha 2,8-sialyl and alpha 2,8-polysialyltransferase activities
      required for their synthesis during oogenesis.
AB  - The developmental expression of the alpha 2,6- and alpha 2,8-linked sialic acid
      (Sia) residues in trout egg polysialoglycoproteins (PSGPs) was studied by
      correlating the temporal expression of these sugar residues, and the prerequisite
      sialyltransferases responsible for their synthesis, during oogenesis. The
      following new findings are reported. 1) Disialylated glycoproteins were
      identified in ovaries 4-6 months prior to ovulation. Three months prior to
      ovulation, a second more highly sialylated glycoprotein appeared. Structural
      studies confirmed that the two glycoproteins were discrete molecular species,
      designated PSGP(low Sia) and PSGP(high Sia), which differed only in their Sia
      content. PSGP(low Sia) contained mostly disialyl (Sia alpha 2,8-Sia alpha 2,6-)
      side chains, whereas PSGP(high Sia) contained alpha 2,8-linked oligo/polySia side
      chains ranging in length from 2 to over 20 Sia residues. The average degree of
      polymerization ([DP]av) was 6. 2) Biosynthetic studies using CMP-[14C]Neu5Ac
      indicated that three sialyltransferase activities were responsible for synthesis
      of the polysialyl residues of PSGPs: (i) alpha-N-acetylgalactosaminide alpha 2,6
      sialyltransferase (alpha 2,6-ST), which catalyzed formation of the Sia residues
      alpha 2,6-linked to the proximal GalNAc residues in asialo-PSGP; (ii) alpha 2,6
      sialoside alpha 2,8-sialyltransferase (alpha 2,8-ST or "initiase"), which
      catalyzed transfer of the first alpha 2,8-Sia residue to the alpha 2,6-linked Sia
      residue; and (iii) an alpha 2,8-polysialyltransferase (alpha 2,8-polyST or
      "polymerase"), responsible for synthesis of the alpha 2,8-linked poly/oligo Sia
      chains in PSGP(high Sia). Expression of these enzyme activities increased in
      accordance with the developmental appearance of each PSGP. 3) Structural
      characterization of the [14C]Sia-labeled side chains of each PSGP at different
      stages of development confirmed that synthesis of the disialyl unit containing a
      single alpha 2,8-Sia residue occurred before alpha 2,8-polysialylation. 4) In
      ovaries, 96% of the sialyltransferase activities were found in the Golgi-derived
      immature cortical vesicles or as soluble enzymes released from the fragile
      vesicles. Less than 4% of the activities were localized in the membrane (Golgi)
      fraction. In mature eggs, the sialyltransferases were also detected as soluble
      enzymes, and within the cortical vesicles.

PMID- 8144615
TI  - Identification of a novel determinant for basic domain-leucine zipper DNA binding
      activity in the acute-phase inducible nuclear factor-interleukin-6 transcription
      factor.
AB  - Nuclear factor-interleukin-6 (NF-IL6), a member of the CCAAT box/enhancer-binding
      protein (C/EBP) family, contains a basic domain-leucine zipper (bZIP) DNA binding
      motif. Controlled protease digestion was used to probe free and DNA-complexed NF
      IL6 protein. Digestion with trypsin in the absence of DNA produced the leucine
      zipper domain (containing residues 303-345). In contrast, digestion of NF-IL6.DNA
      complexes produced a stable domain, spanning residues 266-345, termed the tryptic
      core domain (TCD). The NH2-terminal boundary of the TCD is longer than tryptic
      peptides reported from C/EBP alpha.DNA complexes. Digestion of NF-IL6 with
      endoprotease Asp-N produced a domain smaller than the TCD (NF-IL6 bZIP domains
      (NFBD) (272-345)), a domain identified either in the absence or the presence of
      DNA. Both recombinant peptides bind acute-phase response element DNA in a
      sequence-specific fashion. The equilibrium disassociation constant (Kd) for the
      TCD was 36 +/- 8 nM, whereas the Kd for NFBD (272-345) was 283 +/- 160 nM.
      Moreover, in comparison with the TCD, NFBD (272-345) formed unstable DNA
      complexes with a 15-fold faster off-rate. We conclude that the amino acids
      represented between 266 and 272 termed the complex stabilizing subdomain,
      influences DNA complex formation independent of DNA binding specificity, and may
      be one mechanism for heterogeneity of DNA interaction by C/EBP family members.

PMID- 8144616
TI  - Intracellular Mg2+ movement during muscarinic stimulation. Mg2+ uptake by the
      intracellular Ca2+ store in rat sublingual mucous acini.
AB  - The muscarinic agonist carbachol produces a sustained elevation in the cytosolic
      free Mg2+ concentration ([Mg2+]i) by mobilizing an intracellular Mg2+ pool in rat
      sublingual mucous acini (Zhang, G. H., and Melvin, J.E. (1992) J. Biol. Chem.
      267, 20721-20727). In the present study, we investigated the relationship between
      the agonist-induced mobilization of the intracellular Ca2+ store and Mg2+
      movement in acini loaded with the Ca(2+)-selective chelator bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) by monitoring [Mg2+]i
      using dual wavelength microfluorometry of the Mg(2+)-sensitive fluorescent
      indicator mag-fura-2. The resting [Mg2+]i in BAPTA-loaded acini was comparable to
      unloaded acini (0.36 +/- 0.01 mM (n = 29) versus 0.35 +/- 0.01 mM (n = 119)). In
      contrast to the > 40% sustained increase in [Mg2+]i in unloaded acini, carbachol
      stimulation of BAPTA-loaded acini induced a rapid transient [Mg2+]i decrease
      (approximately 30%), followed by a slower recovery to the prestimulated [Mg2+]i
      in 3-4 min. Furthermore, in Ca(2+)-free medium or when Ca2+ influx was blocked
      with La3+ or Ni2+, carbachol induced a sustained decrease in [Mg2+]i
      (approximately 40%). Reintroducing extracellular Ca2+ resulted in recovery of
      [Mg2+]i, even in the absence of extracellular Mg2+. 8-(Di-ethylamino)octyl 3,4,5
      trimethoxybenzoate, an inhibitor of the inositol 1,4,5-trisphosphate-sensitive
      intracellular Ca2+ release pathway, completely blocked the carbachol-induced
      decrease in [Mg2+]i, whereas thapsigargin, a Ca(2+)-ATPase inhibitor that empties
      the inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store, stimulated a
      decrease in [Mg2+]i. The thapsigargin-induced Mg2+ uptake was into the same
      intracellular pool as that activated by carbachol because stimulation with
      thapsigargin after carbachol did not induce a further decrease in [Mg2+]i. Taken
      together, these results strongly suggest that depletion of the inositol 1,4,5
      trisphosphate-sensitive Ca2+ store activates Mg2+ uptake, most likely to maintain
      charge balance of the intracellular Ca2+ pool.

PMID- 8144617
TI  - Subtype-specific signaling mechanisms of somatostatin receptors SSTR1 and SSTR2.
AB  - Somatostatin regulates diverse cellular effectors, including adenylyl cyclase,
      ion channels, and ion exchangers. We expressed two somatostatin receptor
      subtypes, SSTR1 and SSTR2, stably in mouse fibroblast Ltk- cells and transiently
      in human embryonic kidney HEK293 cells to investigate subtype-specific
      pharmacological and functional properties. The effects of GTP gamma S and
      pertussis toxin on [125I-Tyr11]somatostatin-14 binding indicated that SSTR2 may
      couple exclusively to pertussis toxin-sensitive G proteins, whereas SSTR1 may
      couple to both pertussis-sensitive and -insensitive G proteins. When expressed
      either stably or transiently, both receptor subtypes mediated somatostatin
      inhibition of cAMP accumulation by a pertussis toxin-sensitive mechanism. In
      contrast, only SSTR1 mediated somatostatin inhibition of Na(+)-H+ exchange
      activity, and this action was insensitive to pertussis toxin. We generated two
      chimeric receptors by replacing sequential residues of SSTR2 with cognate
      sequences of SSTR1 to identify molecular determinants unique to SSTR1 that may
      confer coupling to the exchanger. SSTCR4 included a SSTR1 segment encompassing
      determinants within the fifth and sixth hydrophobic domains and the entire third
      cytoplasmic loop, while SSTCR5 contained a SSTR1 segment spanning the second
      through sixth hydrophobic domains, including both second and third cytoplasmic
      loops. Although both chimeric receptors mediated somatostatin inhibition of cAMP
      accumulation, only SSTCR5 mediated the inhibition of Na(+)-H+ exchange activity,
      and this effect was pertussis-insensitive. These findings demonstrate both
      pharmacological and functional differences between SSTR1 and SSTR2. The ability
      of SSTR1 to selectively attenuate Na(+)-H+ exchange activity requires
      determinants outside the third cytoplasmic domain.

PMID- 8144618
TI  - Phenotypic alterations in fos-transgenic mice correlate with changes in Fos/Jun
      dependent collagenase type I expression. Regulation of mouse metalloproteinases
      by carcinogens, tumor promoters, cAMP, and Fos oncoprotein.
AB  - Using specific cDNAs isolated from mouse fibroblasts we determined tissue
      specific expression of different matrix metalloproteinase genes: both stromelysin
      1 and collagenase IV are highly expressed in heart and lung, whereas collagenase
      I is expressed most abundantly in skeletal muscle, kidney, and bone. High basal
      level expression of stromelysin-2 is found in heart and kidney. Like in man and
      rat, the expressions of collagenase I, stromelysin-1, and stromelysin-2 are
      regulated by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and by UV
      irradiation, but not by cAMP. In contrast, the expression of the 72-kDa
      collagenase IV is not affected by either stimuli. We and others have shown
      previously that under cell culture conditions, the regulation of human
      collagenase I is regulated by the transcription factor Fos/Jun (AP-1). Here we
      show that in c-fos transgenic mice transcription of collagenase I is induced in
      thymus, spleen, and, most dominantly, in bone upon overexpression of Fos. Neither
      collagenase IV nor stromelysin-1 or stromelysin-2 expression is affected by c
      Fos. The sites of induced collagenase I expression correlate with the sites of
      Fos-induced long-term cellular alterations in transgenic mice including bone
      remodeling and T cell development. In fact, in the developing bone tumors
      strongly enhanced levels of collagenase I transcripts were detectable. These
      results identify collagenase I as a Fos-regulated gene in vivo and suggest a
      possible role for Fos/Jun heterodimers in establishing the pathological phenotype
      of c-fos transgenic mice.

PMID- 8144619
TI  - Mutational analysis of the traffic ATPase (ABC) transporters involved in uptake
      of eye pigment precursors in Drosophila melanogaster. Implications for structure
      function relationships.
AB  - The white, brown, and scarlet genes of Drosophila melanogaster encode three
      proteins that belong to the Traffic ATPase superfamily of transmembrane permeases
      and are involved in the transport of guanine and tryptophan (precursors of the
      red and brown eye pigments). We have determined the nucleotide sequences of two
      mutant white alleles (wco2 and wBwx) that cause reduced red pigmentation but have
      no effect on brown pigmentation. In wco2 the effect is only observed when
      interacting with the bw6 allele or a newly isolated allele (bwT50). These alleles
      of the brown gene were cloned and sequenced. In wco2 the codon for glycine 588 is
      changed to encode serine; in wBwx the triplet ATC encoding isoleucine 581 is
      deleted; asparagine 638 is changed to threonine in bw6, and glycine 578 is
      changed to aspartate in bwT50. No other relevant changes to the gene structures
      were detected. P-element-mediated germline transduction was used to construct a
      fly strain containing a white gene with a mutation of the nucleotide binding
      domain. Such flies had white eyes, indicating that the mutated white gene was
      unable to support either guanine or tryptophan transport. The implications of
      these mutations are discussed in terms of a model of the Drosophila pigment
      precursor transport system.

PMID- 8144620
TI  - Expression in Escherichia coli of genes encoding the E1 alpha and E1 beta
      subunits of the pyruvate dehydrogenase complex of Bacillus stearothermophilus and
      assembly of a functional E1 component (alpha 2 beta 2) in vitro.
AB  - The E1 alpha and E1 beta subunits of the pyruvate decarboxylase (E1) component of
      the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus
      were produced from two genes overexpressed separately in Escherichia coli. A
      functional E1 enzyme was generated from disrupted mixtures of cells containing
      the separately overexpressed E1 alpha and E1 beta genes. The purified E1 enzyme
      exhibited an apparent molecular mass of 150,000 Da, consistent with an alpha 2
      beta 2 structure. The Km for pyruvate and kcat (30 degrees C) were found to be
      0.9 +/- 0.2 microM and 0.47 +/- 0.03 s-1, respectively. The purified E1 alpha
      subunit existed as a monomer (42,000 Da), whereas the E1 beta subunit existed
      mainly (95%) in a tetrameric form (145,000 Da). Mixing equimolar amounts of the
      pure recombinant E1 alpha and E1 beta subunits in vitro generated a functional E1
      enzyme with a molecular mass and an E1 activity similar to those of the E1(alpha
      2 beta 2) enzyme purified from disrupted mixtures of cells containing
      individually expressed subunits. Mixing individual subunits in vitro with one of
      the subunits in excess resulted in complete assembly of the lesser subunit into
      the intact E1 (alpha 2 beta 2) enzyme. Thus, no chaperonin is needed in vitro to
      promote the assembly of the separate subunits to form the E1 component of the
      pyruvate dehydrogenase multienzyme complex of B. stearothermophilus.

PMID- 8144621
TI  - The human chorionic somatomammotropin gene enhancer is composed of multiple DNA
      elements that are homologous to several SV40 enhansons.
AB  - Previous studies indicate that a human chorionic somatomammotropin (hCS) gene
      enhancer (CSEn) associated with the growth hormone (hGH) gene locus is involved
      in directing cell-specific expression of the hCS genes in placenta. In the
      current studies, we report a detailed structural analysis of this enhancer. CSEn
      stimulated transcription of a variety of promoters, including the hCS, human
      growth hormone, thymidine kinase, and Rous sarcoma virus promoters, in human
      choriocarcinoma cell lines (BeWo and JEG-3) but not HeLa cells or rat
      somatolactotrophes (GC). Maximal enhancer activity was confined to a 242-base
      pair DNA segment. Of several CSEn subfragments, only the En 57/242 subfragment
      retained activity (33.5% wild-type). The CSEn DNA sequence contained direct and
      inverted repeat motifs and sequences related to the SV40 enhansons, GT-IIC, GT-I,
      and SphI/SphII. DNase I footprint analysis revealed that most of these sites were
      protected by nuclear proteins derived from BeWo, JEG-3, HeLa, and GC cells. Site
      specific block mutation of the GT-IIC-related and inverted repeat motifs
      virtually abolished enhancer activity, and mutation of all but the GT-I-related
      motif resulted in significant loss (30-60%) of activity. These data demonstrate
      that the CS enhancer is comprised of multiple elements related to SV40 enhansons
      that interact cooperatively to generate enhancer function.

PMID- 8144622
TI  - Molecular mechanism of regulation of yeast plasma membrane H(+)-ATPase by
      glucose. Interaction between domains and identification of new regulatory sites.
AB  - The carboxyl terminus of yeast plasma membrane H(+)-ATPase is an autoinhibitory
      domain, and its effect is counteracted by modification of the enzyme triggered by
      glucose metabolism (Portillo, F., Larrinoa, I. F., and Serrano, R. (1989) FEBS
      Lett. 247, 381-385). To identify interacting domains involved in this regulation,
      we have performed intragenic suppressor analysis. A double mutation at the
      carboxyl terminus (S911A/T912A) results in no activation of the ATPase by glucose
      and lack of yeast growth on this sugar (Portillo, F., Eraso, P., and Serrano, R.
      (1991) FEBS Lett. 287, 71-74). Random in vitro mutagenesis of this mutant ATPase
      gene resulted in 29 revertants. Six corresponded to full revertants of the
      initial double mutation. Fourteen suppressor (second-site) mutations are located
      within three functional domains of the enzyme. Four mutations (A165V,
      V169I/D170N, A350T, and A351T) are localized at the cytoplasmic ends of predicted
      transmembrane helices 2 and 4; six mutations (P536L, A565T, G587N, G648S, P669L,
      and G670S) map within the proposed ATP binding domain, and the other four
      substitutions (P890opa, S896F, R898K, and M907I) are located at the carboxyl
      terminus. These results demonstrate the interaction, direct or indirect, between
      these three domains far apart in the linear sequence of the ATPase. All the
      second-site mutations caused constitutive activation of the ATPase in the absence
      of glucose metabolism. Second-site mutations at the carboxyl terminus were close
      to Ser-899 and suggested phosphorylation of this amino acid during glucose
      activation. Accordingly, the introduction of a negative charge, in a S899D mutant
      constructed by site-directed mutagenesis, partially mimics the glucose effect on
      the ATPase.

PMID- 8144623
TI  - The dephosphorylation reaction of the Ca(2+)-ATPase from plasma membranes.
AB  - The breakdown of phosphoenzyme (EP) of the Ca(2+)-ATPase from pig red blood cell
      membranes was studied at 37 degrees C by means of a rapid chemical quenching
      technique. When the enzyme was phosphorylated with [gamma-32P]ATP in media
      without added MgCl2, all the EP formed disappeared along two single exponential
      curves, a rapid one with k(app) = 90 +/- 10 s-1 and a slow one with k(app) = 0.7
      +/- 0.3 s-1. The amount of EP involved in each reaction was close to 50% of the
      EP present at the beginning. Only EP of rapid breakdown could account for the
      steady-state hydrolysis of ATP observed under the same experimental conditions.
      ADP accelerated the slow reaction 45-fold (k(app) = 31 +/- 9 s-1) with K0.5 = 740
      +/- 120 microM as if this reaction represented the decay of CaE1P, which donated
      its phosphate to water slowly in the forward direction and rapidly to ADP in the
      reverse direction of the cycle. Combination of Mg2+ with K0.5 = 26.3 +/- 5.0
      microM at a single class of site in E1 before phosphorylation increased EP of
      rapid breakdown at the expense of ADP-sensitive EP so that, at nonlimiting
      concentrations of Mg2+ in the phosphorylation media, all EP decomposed at high
      rate. Rapid decomposition was observed even with enough CDTA to chelate most of
      the Mg2+ remaining from phosphorylation, suggesting that the role of Mg2+ during
      dephosphorylation was to accelerate the transition CaE1P-->CaE2P, preparing EP
      for hydrolysis. The combination of ATP at a single class of site with Km = 845 +/
      231 microM accelerated the hydrolysis of CaE2P. Calmodulin alone had no effects
      on dephosphorylation but enhanced acceleration of hydrolysis of CaE2P by ATP
      making the decay of EP under these conditions the fastest among those measured.
      Comparison of the rates of dephosphorylation of EP made in the presence of Mg2+
      with those of steady-state Ca(2+)-ATPase activity with and without calmodulin
      showed that the transition CaE1P-->CaE2P and decomposition of CaE2P by hydrolysis
      are compatible with their role as obligatory intermediate reactions in the cycle
      of hydrolysis of ATP by the Ca(2+)-ATPase.

PMID- 8144624
TI  - Monoclonal antibodies FK1 and WF6 define two neighboring ligand binding sites on
      Torpedo acetylcholine receptor alpha-polypeptide.
AB  - Previous studies have identified the sequence region flanking the invariant
      vicinal cysteinyl residues at positions 192 and 193 of the nicotinic
      acetylcholine receptor alpha-subunit as containing major elements of the binding
      site for acetylcholine and its agonists and antagonists, including antibody WF6
      (Conti-Tronconi, B. M., Diethelm, B. M., Wu, X., Tang, F., Bertazzon, T.,
      Schroder, B., Reinhardt-Maelicke, A., and Maelicke, A. (1991) Biochemistry 30,
      2575-2584). Recently we have shown that the sequence region flanking lysine alpha
      125 contains elements of the binding site for physostigmine and related ligands,
      including antibody FK1 (Schrattenholz, A., Godovac-Zimmerman, J., Schafer, H.-J.,
      Albuquerque, E. X., and Maelicke, A. (1993) Eur. J. Biochem. 216, 671-677). Here
      we report the identification by enzyme-linked immunosorbent assay techniques,
      employing fragments of the Torpedo nicotinic acetylcholine receptor alpha-subunit
      N-terminal region and a panel of synthetic peptides matching in sequence
      preselected portions of this subunit, of the sequence regions alpha 118-145 and
      alpha 181-216 as contributing to the FK1 epitope. Of the synthetic peptides
      employed, alpha 118-137 displayed the highest affinity of FK1 binding. Binding of
      FK1 and WF6 to single residue-substituted analogs of the sequence alpha 181-200
      indicated that the two antibodies have different attachment point patterns within
      this sequence region. These results, and those of ligand competition studies,
      suggest that the binding sites for FK1 and physostigmine, and those of WF6 and
      acetylcholine, are within the same general region of the receptor's three
      dimensional structure. The sites neighbor each other, with limited overlap in the
      case of occupation by high molecular weight ligands.

PMID- 8144625
TI  - Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus
      melanoma cells and identification of a source for the physiological ligand.
AB  - The melanoma-inducing gene of Xiphophorus fish encodes the Xmrk receptor tyrosine
      kinase. Using a highly specific antiserum produced against the recombinant
      receptor expressed with a baculovirus, it is shown that Xmrk is the most abundant
      phosphotyrosine protein in fish melanoma and thus highly activated in the tumors.
      Studies on a melanoma cell line revealed that these cells produce an activity
      that considerably stimulates receptor autophosphorylation. The stimulating
      activity induces receptor down-regulation and can be depleted from the melanoma
      cell supernatant by the immobilized recombinant receptor protein. The fish
      melanoma cells can thus be considered autocrine tumor cells providing a source
      for future purification and characterization of the Xmrk ligand.

PMID- 8144626
TI  - Cloning the structural gene for the 49-kDa form of exoenzyme S (exoS) from
      Pseudomonas aeruginosa strain 388.
AB  - We report the purification and proteolytic characterization of the 49-kDa form of
      exoenzyme S and the cloning of the structural gene for the 49-kDa form of
      exoenzyme S (exoS). The 49-kDa form of exoenzyme S was purified from SDS
      polyacrylamide gels. Conditions were established that allowed efficient trypsin
      digestion of the 49-kDa form of exoenzyme S. Amino acid sequence determination of
      the amino terminus and tryptic peptides of the 49-kDa form of exoenzyme S allowed
      the generation of degenerate oligonucleotides, which were used to amplify DNA
      encoding an amino-terminal sequence and an internal sequence of the 49-kDa form
      of exoenzyme S. These DNA fragments were used to clone the entire structural gene
      for the 49-kDa form of exoenzyme S (exoS) from a cosmid library of Pseudomonas
      aeruginosa strain 388. The 49-kDa form of exoenzyme S (ExoS) is predicted to be a
      453 amino acid protein. The predicted amino acid sequence indicates that ExoS is
      secreted from Pseudomonas without cleavage of an amino-terminal sequence. BESTFIT
      analysis identified three regions of alignment between ExoS and the active site
      of Escherichia coli heat-labile enterotoxin. One region of homology appears to be
      shared among several members of the family of bacterial ADP-ribosyltransferases.

PMID- 8144627
TI  - cDNA cloning and sequencing of mouse mastocytoma glucosaminyl N-deacetylase/N
      sulfotransferase, an enzyme involved in the biosynthesis of heparin.
AB  - A 110-kDa protein involved in heparin biosynthesis in mouse mastocytoma cells was
      previously shown to express both glucosaminyl N-deacetylase and N
      sulfotransferase activity. In this study, the complete nucleotide sequence
      corresponding to this protein is reported. The mRNA, estimated to contain 3.9
      kilobases encodes a protein with an M(r) of 101,092. The predicted domain
      structure of the protein resembles those of previously characterized Golgi
      proteins with an N-terminal cytoplasmic tail, a single membrane-spanning domain,
      and a large catalytic domain linked to the transmembrane domain through a "stem
      region." Comparison of the deduced amino acid sequence of the mouse mastocytoma
      protein and a previously cloned similar enzyme from rat liver demonstrated that
      while large portions of the proteins, corresponding essentially to the putative
      catalytic domains, were closely related, other portions, in particular in the N
      terminal parts, were markedly different. The divergence was not due to species
      differences since two separate mouse transcripts could be identified that
      hybridized with probes specific for the two proteins. Also, functional
      differences were noted since the mastocytoma enzyme, contrary to the liver
      enzyme, requires a polycation cofactor for expression of N-deacetylase activity.
      The results are discussed in relation to the structural properties of heparin and
      heparan sulfate.

PMID- 8144628
TI  - The third helix of the Antennapedia homeodomain translocates through biological
      membranes.
AB  - The 60-amino acid long homeodomain of Antennapedia crosses biological membranes
      by an energy-independent mechanism, a phenomenon abolished by directed
      mutagenesis within the polypeptide C-terminal region. This finding led us to
      study the internalization of several chemically synthesized peptides derived from
      the third helix of the homeodomain. We report here that a polypeptide of 16 amino
      acids in length corresponding to the third helix of the homeodomain deleted of
      its N-terminal glutamate is still capable of translocating through the membrane.
      A longer peptide of 20 amino acids also translocates, whereas shorter peptides
      (15 amino acids) are not internalized by the cells. As is also the case for the
      entire homeodomain, the 20- and 16-amino acid long peptides are internalized at 4
      degrees C, suggesting an energy-independent mechanism of translocation not
      involving classical endocytosis. The two translocated peptides can be recovered,
      intact, within the cells, strongly suggesting that they are not targeted to the
      lysosomal compartment. Finally, substitution of two tryptophans by two
      phenylalanines strongly diminishes translocation, raising the possibility that
      the internalization of the third helix is not solely based on its general
      hydrophobicity.

PMID- 8144629
TI  - The sequences of human and bovine genes of the phosphate carrier from
      mitochondria contain evidence of alternatively spliced forms.
AB  - The sequences of the human and bovine genes for the phosphate carrier from the
      inner membranes of mitochondria have been determined. The genes have similar
      structures and each is divided into nine exons. In both genes, two exons, named
      IIIA and IIIB, are closely related, and they appear to the alternatively spliced.
      The human exon IIIB sequence is found in a published human heart cDNA sequence,
      and bovine exon IIIA forms part of a published bovine heart cDNA sequence. By
      further examination of the human heart cDNA library, sequences arising from both
      alternatively spliced forms of the phosphate carrier have been characterized.
      Both forms were also found in several bovine tissues, but the ratios of
      expression of the two forms varied. The form containing exon IIIA was expressed
      most highly in bovine heart and liver, less highly in brain and kidney, and only
      in low amounts in lung. The opposite hierarchy was found for the form containing
      exon IIIB; it was most highly expressed in lung and least in heart and liver. The
      alternative splicing mechanism affects amino acids 4-45 of the mature phosphate
      carrier protein, which is believed to form one of six transmembrane segments of
      the phosphate carrier and to emerge into a large extramembranous loop. The
      alternative splicing mechanism changes 13 and 11 amino acids in the human and
      bovine carrier proteins, respectively. As the function of this region of the
      phosphate carrier is not known, the effects of the changes on carrier function
      are not understood at present.

PMID- 8144630
TI  - Functional alpha-tropomyosin produced in Escherichia coli. A dipeptide extension
      can substitute the amino-terminal acetyl group.
AB  - Unlike the muscle protein, alpha-tropomyosin expressed in Escherichia coli does
      not bind actin, does not exhibit head-to-tail polymerization, and does not
      inhibit actomyosin ATPase activity in the absence of troponin. The only chemical
      difference between recombinant and muscle tropomyosins is that the first
      methionine is not acetylated in the recombinant protein (Hitchcock-De-Gregori,
      S.E., and Heald, R. W. (1987) J. Biol. Chem. 262, 9730-9735). We expressed three
      fusion tropomyosins in E. coli with 2, 3, and 17 amino acids fused to its amino
      terminus. All three fusions restored actin binding, head-to-tail polymerization,
      and the capacity to inhibit the actomyosin ATPase to these unacetylated
      tropomyosins. Unlike larger fusions, the small fusions of 2 and 3 amino acids do
      not interfere with regulatory function. Therefore the presence of a fused
      dipeptide at the amino terminus of unacetylated tropomyosin is sufficient to
      replace the function of the N-acetyl group present in muscle tropomyosin. A
      structural interpretation for the function of the acetyl group, based on our
      results and the coiled coil structure of tropomyosin, is presented.

PMID- 8144631
TI  - SH-PTP2/Syp SH2 domain binding specificity is defined by direct interactions with
      platelet-derived growth factor beta-receptor, epidermal growth factor receptor,
      and insulin receptor substrate-1-derived phosphopeptides.
AB  - Signaling by tyrosine kinases involves direct associations between proteins with
      Src homology 2 (SH2) domains and sites of tyrosine phosphorylation. Specificity
      in signaling pathways results in part from inherent selectivity in interactions
      between particular SH2 domains and phosphopeptide sequences. The cytoplasmic
      phosphotyrosine phosphatase SH-PTP2 (Syp, PTP 1D, PTP-2C) contains two SH2
      domains (N and C) which mediate its association with and activation by the
      platelet-derived growth factor (PDGF) and epidermal growth factor receptors and
      IRS-1. We have developed a competitive phosphopeptide binding assay to analyze
      specificity of the SH-PTP2 N-SH2 domain for phosphorylation sites of these
      phosphoproteins. The sequence surrounding Tyr1009 bound with greatest affinity
      (ID50 = 14 microM) of eight PDGF receptor-derived phosphopeptides tested. No
      peptides corresponding to known epidermal growth factor receptor phosphorylation
      sites bound with high affinity. However, an alternative sequence surrounding
      Tyr954 bound tightly (ID50 = 21 microM). Of the 13 IRS-1-related peptides
      analyzed, sequences surrounding Tyr546, Tyr895, and Tyr1172 bound with highest
      affinity (ID50 = 11, 4, and 1 microM, respectively). Alternative phosphopeptides
      generally bound with much weaker affinity (ID50 > 150 microM). These findings are
      consistent with recent mutational analyses of the PDGF receptor and predict site
      specific interactions between SH-PTP2 and each of these phosphoproteins.
      Comparisons between peptide sequences suggest that the N-terminal SH2 domain of
      SH-PTP2 binds with highest affinity to phosphotyrosine (pY) followed by a beta
      branched residue (Val, Ile, Thr) at pY+1 and a hydrophobic residue (Val, Leu,
      Ile) at pY+3 positions. Peptide truncation studies also indicate that residues
      outside of the pY-1 to pY+4 motif are required for high affinity interactions.

PMID- 8144632
TI  - Response of human fibroblasts to hypertonic stress. Cell shrinkage is
      counteracted by an enhanced active transport of neutral amino acids.
AB  - Regulatory volume increase (RVI) has been studied in cultured human fibroblasts
      (CHF) incubated in a complete hypertonic growth medium (400 mosmol/kg). After the
      initial cell shrinkage induced by hypertonic treatment, cells recover their
      volume almost completely within 3 h. This RVI response is associated with a
      marked increase of the cell content of free amino acids. The cell content of
      potassium increases only slightly. Chromatographic analysis of the intracellular
      amino acid pool shows that the RVI-associated increase in cell amino acids is
      mainly a result of changes in the L-glutamine content. The intracellular
      accumulation of the analog 2-methylaminoisobutyric acid, a specific substrate of
      transport system A, is increased in CHF undergoing RVI. Hypertonic treatment
      causes an immediate and sustained cell hyperpolarization, as demonstrated by
      changes in the trans-membrane distribution ratio of L-arginine and in the
      fluorescence of the potential-sensitive dye bis-1,3-diethylthiobarbiturate
      trimethineoxonol. Because of cell hyperpolarization, at the end of RVI the trans
      membrane gradient of the sodium electrochemical potential is higher than that of
      the control. The increase in the extracellular potassium concentration ([K+]out =
      40 mM) abolishes the hyperpolarization induced by hypertonic treatment and delays
      volume recovery. Cycloheximide suppresses RVI at a high but not at physiologic
      [K+]out. It is proposed that CHF counteract hypertonic shrinkage through an
      enhanced accumulation of substrates of transport system A sustained, initially,
      by an increase in the energy available for transport and, subsequently, also by
      the synthesis of new site A carriers.

PMID- 8144633
TI  - Asymmetrical topology of diether- and tetraether-type polar lipids in membranes
      of Methanobacterium thermoautotrophicum cells.
AB  - We investigated the distribution of diether polar lipids between the inner and
      outer leaflets of the membrane of Methanobacterium thermoautotrophicum comparing
      the orientation of tetraether polar lipids, which constitute a monolayer in the
      same membrane. Three kinds of reactions were employed for intact cells or
      protoplasts and unsealed membrane fragments prepared from the organism:
      glycosidase digestion for glycolipids, NaIO4 oxidation for glycolipids and
      inositol lipids, and trinitrophenylation for aminophospholipids. The results
      indicated that (a) most gentiobiose residues of both diether and tetraether polar
      lipids were exposed on the outside of the cells; (b) serine and inositol residues
      of both diether and tetraether polar lipids were mainly oriented to the
      cytoplasmic surface of the membrane; and (c) approximately 80% of
      archaetidylethanolamine (diether type) was distributed in the outer leaflet of
      the membrane bilayer, while only 25% of the ethanolamine residue of gentiobiosyl
      caldarchaetidylethanolamine (tetraether type) was oriented to the outer surface
      of the membrane. These results, except for ethanolamine lipids, are consistent
      with the hypothesis that the tetraether polar lipids are synthesized from the
      corresponding diether polar lipid precursors that have been already substituted
      by polar groups in the membrane by head-to-head condensation without
      rearrangement of lipids.

PMID- 8144634
TI  - Identification of protein receptor for Clostridium botulinum type B neurotoxin in
      rat brain synaptosomes.
AB  - The protein receptor for Clostridium botulinum type B neurotoxin was purified 340
      fold from rat synaptosomes by successive chromatography on DEAE-Sepharose, phenyl
      Toyopearl, and heparin-Toyopearl columns. 125I-Labeled neurotoxin bound to lipid
      vesicles containing the protein receptor and ganglioside GT1b or GD1a. The
      reconstituted receptor showed the same affinities as the native receptor on
      synaptosomes. Chemical cross-linking of 125I-toxin to the receptor in the
      presence of gangliosides resulted in formation of a cross-linked product of 161
      kDa under reducing conditions. Cross-linking was specific, as it was inhibited by
      the presence of excess unlabeled toxin. A monoclonal antibody against the
      purified 58-kDa receptor protein and a monoclonal antibody against the heavy
      chain (103 kDa) of the neurotoxin reacted with the cross-linked product of 161
      kDa in immunoblotting experiments. We determined partial amino acid sequences of
      the 58-kDa protein, which were identical to synaptotagmin, a synaptic vesicle
      membrane protein. In addition, the monoclonal antibody against the 58-kDa
      receptor protein recognized recombinant rat synaptotagmin. These results suggest
      that synaptotagmin in association with ganglioside GT1b or GD1a may be a natural
      receptor for C. botulinum type B neurotoxin at the nerve terminals.

PMID- 8144635
TI  - Spectroscopic properties of desulfoferrodoxin from Desulfovibrio desulfuricans
      (ATCC 27774).
AB  - Desulfoferrodoxin, a non-heme iron protein, was purified previously from extracts
      of Desulfovibrio desulfuricans (ATCC 27774) (Moura, I., Tavares, P., Moura, J. J.
      G., Ravi, N., Huynh, B. H., Liu, M.-Y., and LeGall, J. (1990) J. Biol. Chem. 265,
      21596-21602). The as-isolated protein displays a pink color (pink form) and
      contains two mononuclear iron sites in different oxidation states: a ferric site
      (center I) with a distorted tetrahedral sulfur coordination similar to that found
      in desulforedoxin from Desulfovibrio gigas and a ferrous site (center II)
      octahedrally coordinated with predominantly nitrogen/oxygen-containing ligands. A
      new form of desulfoferrodoxin which displays a gray color (gray form) has now
      been purified. Optical, electron paramagnetic resonance (EPR), and Mossbauer data
      of the gray desulfoferrodoxin indicate that both iron centers are in the high
      spin ferric states. In addition to the EPR signals originating from center I at g
      = 7.7, 5.7, 4.1, and 1.8, the gray form of desulfoferrodoxin exhibits a signal at
      g = 4.3 and a shoulder at g = 9.6, indicating a high-spin ferric state with E/D
      approximately 1/3 for the oxidized center II. Redox titrations of the gray form
      of the protein monitored by optical spectroscopy indicate midpoint potentials of
      +4 +/- 10 and +240 +/- 10 mV for centers I and II, respectively. Mossbauer
      spectra of the gray form of the protein are consistent with the EPR finding that
      both centers are high-spin ferric and can be analyzed in terms of the EPR
      determined spin Hamiltonian parameters. The Mossbauer parameters for both the
      ferric and ferrous forms of center II are indicative of a mononuclear high spin
      iron site with octahedral coordination and predominantly nitrogen/oxygen
      containing ligands. Resonance Raman studies confirm the structural similarity of
      center I and the distorted tetrahedral FeS4 center in desulforedoxin and provide
      evidence for one or two cysteinyl-S ligands for center II. On the basis of the
      resonance Raman results, the 635 nm absorption band that is responsible for the
      gray color of the oxidized protein is assigned to a cysteinyl-S-->Fe(III) charge
      transfer transition localized on center II. The novel properties and possible
      function of center II are discussed in relation to those of mononuclear iron
      centers in other enzymes.

PMID- 8144636
TI  - Protein kinase C alpha mediates phospholipase D activation by nucleotides and
      phorbol ester in Madin-Darby canine kidney cells. Stimulation of phospholipase D
      is independent of activation of polyphosphoinositide-specific phospholipase C and
      phospholipase A2.
AB  - Protein kinase C (PKC) has been implicated in the activation of phospholipase D
      (PLD) in a number of systems. By antisense technology, we have "knocked out"
      alpha and beta isoforms of PKC to study the role of these isoforms in PLD
      activation in Madin-Darby canine kidney (MDCK) cells. To this end, we have
      studied PLD activation by phorbol 12-myristate 13-acetate (PMA), ATP, UTP, and 2
      methylthio-ATP in cells labeled with [3H]palmitic acid. [3H]Phosphatidylethanol
      (PEt) production catalyzed by PLD in the presence of ethanol was time- and
      concentration-dependent in PMA- and nucleotide-stimulated cells. In Ca(2+)-free
      medium, [3H]PEt accumulation was diminished for all stimuli assayed. Treatment of
      cells with chelerythrine, an inhibitor of PKC, and phorbol ester down-regulation
      of PKC inhibited [3H]PEt production by both PMA and nucleotides. In cells
      transfected with antisense PKC alpha or both PKC alpha and PKC beta, PLD
      activation was inhibited by both PMA and nucleotides, whereas in cells
      transfected with antisense PKC beta, PLD activation was similar to that of
      control cells. Moreover, inhibition of polyphosphoinositide-specific PLC (by
      neomycin) or of release of arachidonic acid and arachidonic acid metabolites (by
      nordihydroguaiaretic acid or by indomethacin) failed to decrease [3H]PEt
      accumulation in PMA- and nucleotide-stimulated MDCK-D1 cells. From these data, we
      conclude that in MDCK-D1 cells PMA and nucleotide receptors utilize PKC alpha to
      regulate PLD activity and that PLD activation is independent of the activation of
      polyphosphoinositide-specific PLC and phospholipase A2-mediated release of
      arachidonic acid or arachidonic acid metabolites.

PMID- 8144637
TI  - Regulation of fluorescent fatty acid transfer from adipocyte and heart fatty acid
      binding proteins by acceptor membrane lipid composition and structure.
AB  - Adipocyte and heart fatty acid binding proteins (A-FABP and H-FABP) are closely
      related members of the FABP family. Unlike the more distantly related liver FABP,
      these FABP have been proposed to transfer free fatty acids to model membranes by
      a collisional mechanism (Wootan, M. G., Bernlohr, D. A., and Storch, J. (1993)
      Biochemistry 32, 8622-8627; Kim, H. K., and Storch, J. (1992) J. Biol. Chem. 267,
      20051-20056). Collisional transfer requires that the acceptor membranes interact
      with FABP during the transfer process. We, therefore, examined whether the
      acceptor membrane structure and lipid composition regulate the rate of
      anthroyloxy-labeled palmitate (2AP) transfer from A- and H-FABP, using a
      fluorescence resonance energy transfer assay. The results showed that 2AP
      transfer from A- and H-FABP was more rapid to acceptor vesicles containing acidic
      phospholipids and was slower to positively charged membranes. In addition, the
      rate of 2AP transfer from A- and H-FABP was enhanced by unsaturation of the
      phosphatidylcholine acyl chains and was slowed by the presence of cholesterol or
      sphingomyelin in the acceptor membranes. These latter changes were small but of a
      similar magnitude and together suggest that fatty acid transfer from A- and H
      FABP was slower to membranes of greater lipid order. Since transfer by an aqueous
      diffusion mechanism would be unaffected by acceptor membrane properties, these
      studies strengthen the hypothesis that free fatty acid transfer from A- and H
      FABP to membranes occurs via a collisional mechanism.

PMID- 8144638
TI  - Multiple forms of the human tyrosine phosphatase RPTP alpha. Isozymes and
      differences in glycosylation.
AB  - Among all the receptor-linked protein-tyrosine-phosphatase RPTP alpha clones
      described from mammalian tissues, one differed in that it encoded a 9-amino-acid
      insert 3 residues upstream from the transmembrane segment (Kaplan, R., Morse, B.,
      Huebner, K., Croce, C., Howk, R. Ravera, M., Ricca, G., Jaye, M., and
      Schlessinger, J. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 7000-7004). Using the
      polymerase chain reaction technique, simultaneous expression of both isoforms was
      demonstrated in human T-cell and vascular smooth muscle libraries, as well as in
      the A431 human epidermal cancer cell line. Following transient expression in COS
      1 cells, each isoform gave rise to two proteins of 100 and 130 kDa, respectively.
      Endoglycosidase treatment showed that the 100-kDa species corresponded to a
      molecule exclusively glycosylated on N-residues, whereas the 130-kDa species
      contained both, N- and O-linked carbohydrates. Pulse-chase experiments
      demonstrated that the smaller RPTP alpha protein is a precursor of the larger
      one. A high affinity antibody was generated that recognizes the immature protein
      only; however, both proteins can be detected by Western blot analysis after a
      simple chemical hydrolysis. Following Superose 12 chromatography, the 100- and
      130-kDa species of RPTP alpha emerged as 200- and 340-kDa proteins, respectively.
      Both species exhibited similar enzymatic activities as determined with a peptide
      substrate in immunoprecipitates.

PMID- 8144639
TI  - Identification of phosphorylation sites in rat liver CTP: phosphocholine
      cytidylyltransferase.
AB  - CTP:phosphocholine cytidylyltransferase (CT) is an important regulatory enzyme in
      phosphatidylcholine biosynthesis. The enzyme exists as a soluble, inactive form
      that is highly phosphorylated; activation of the enzyme is accompanied by
      dephosphorylation and translocation to the membrane. We have used a recombinant
      baculovirus clone to obtain CT labeled in vivo with 32PO4. The tryptic
      phosphopeptide pattern of the baculovirus-expressed CT was the same as for CT
      expressed in mammalian cells, indicating that insect cells modify the same
      phosphorylation sites as do mammalian cells. 32PO4-labeled, baculovirus-expressed
      CT was digested with trypsin and the peptides purified by reversed-phase high
      performance liquid chromatography. Phosphoamino acid analysis of the complete
      protein as well as individual peptides revealed that only serine residues were
      phosphorylated. Sequence analysis of purified radioactive peptides revealed that
      phosphorylation of CT was confined to the carboxyl-terminal region and that all
      or nearly all Ser residues from Ser315 to the carboxyl terminus were labeled.
      Ser315, Ser319, Ser329, Ser323, Ser331, Ser343, and Ser347 all reside in
      potential sites for proline-directed kinases. Two other phosphorylated serine
      residues, Ser315 and Ser333, are found within protein kinase C consensus
      phosphorylation sites. Ser321, Ser322, Ser333, Ser345, Ser346, Ser350, Ser352,
      and Ser362 were also found to be phosphorylated. Serine362 resides within a
      putative casein kinase II phosphorylation site, and there are five potential
      sites for phosphorylation by glycogen synthase kinase 3. Identification of these
      sites will allow investigations that focus on the establishment of the
      physiological function of phosphorylation at each site.

PMID- 8144640
TI  - Microsomal retinoic acid metabolism. Effects of cellular retinoic acid-binding
      protein (type I) and C18-hydroxylation as an initial step.
AB  - This report extends our observation that cellular retinoic acid-binding protein
      type I (CRABP) serves as substrate for retinoic acid metabolism by testis
      microsomes. Retinoic acid bound to excess CRABP was metabolized at 70% of the
      unbound retinoic acid rate with testis microsomes and at the same rates as
      unbound retinoic acid with kidney and lung microsomes. Chromatography of testis,
      lung, kidney, and liver microsomal incubations provided two sets of metabolites
      each, P1 and P2. The composition of P2 was characteristic of the individual
      tissue. CRABP had modest quantitative affects on P2 composition, but did not
      affect P2 qualitatively. Retinoids bound to CRABP, isolated from a testis
      microsomal incubation, consisted of 50% retinoic acid, 32% P1 and 17% P2,
      suggesting that CRABP may bind retinoic acid metabolites in vivo. The effect of
      CRABP on the rate of metabolism was retinoid specific. Two major components of
      P2, 4-hydroxy-retinoic acid and 4-oxo-retinoic acid, when bound to CRABP were
      metabolized slowly, if at all, by testis microsomes, in contrast to CRABP-bound
      retinoic acid which had an elimination t1/2 of 40 min. Unbound retinoic acid, 4
      hydroxy-retinoic acid, and 4-oxo-retinoic acid had elimination t1/2 values of 35,
      40, and 9 min, respectively. Reduced metabolism of CRABP-bound C4-derivatized
      retinoids suggests pathways of retinoic acid metabolism besides the one initiated
      by C4-hydroxylation. This was corroborated by identification of 18-hydroxy
      retinoic acid as a testis, lung, and liver microsomal retinoic acid metabolite.
      Ketoconazole inhibited the metabolism by testis microsomes of free and CRABP
      bound retinoic acid with IC50 values of 2 and 0.7 microM, respectively, denoting
      catalysis by cytochrome P-450. These results indicate that cloistering retinoic
      acid in CRABP, while permitting metabolism, may operate throughout CRABP
      expressing tissues as a mechanism of controlling the concentrations of free
      retinoic acid.

PMID- 8144641
TI  - Identification of a vitamin D-responsive element in the 5'-flanking region of the
      rat 25-hydroxyvitamin D3 24-hydroxylase gene.
AB  - The 5'-flanking region of the rat vitamin D3 24-hydroxylase (P450cc24) gene was
      examined and a vitamin D-responsive element (VDRE) responsible for the 1 alpha,25
      dihydroxyvitamin D3 (1,25-(OH)2D3) enhancement was identified. Unidirectional
      deletion analyses of the 5'-flanking region indicated that the region [-167/-102]
      is involved in vitamin D responsiveness. Further functional analyses showed that
      the segment [-204/-129] conferred the hormone responsiveness in an orientation
      independent manner when it was placed upstream to the heterologous thymidine
      kinase promoter or the rabbit beta-globin promoter. The segment [-204/-129]
      contained two direct repeat motifs homologous to other VDREs found in the
      osteocalcin and osteopontin genes. Synthetic oligonucleotides containing the
      putative VDRE were used for functional analyses and gel mobility shift assays.
      The proximal [-151/-137], but not the distal [-169/-155] direct repeat activated
      the transcription in response to 1,25-(OH)2D3 through the beta-globin promoter.
      Furthermore, the proximal direct repeat formed a complex with the vitamin D
      receptor and a nuclear accessory factor(s) from COS cells (or retinoid X
      receptor) in the presence of 1,25-(OH)2D3. These results indicate that a direct
      repeat motif, AGGTGAgt-gAGGGCG, located at -151 base pairs upstream in the
      antisense strand binds to a heterologous dimer consisting of the VDR occupied
      with 1,25-(OH)2D3 and the nuclear accessory factor and that it plays a critical
      role in mediating the vitamin D enhancement of the rat P450cc24 gene expression.

PMID- 8144642
TI  - Modulation of transforming growth factor beta receptors of rat lipocytes during
      the hepatic wound healing response. Enhanced binding and reduced gene expression
      accompany cellular activation in culture and in vivo.
AB  - Activation of lipocytes, characterized by increased proliferation and
      fibrogenesis, is a central feature of the hepatic wound healing response. We have
      examined whether modulation of receptors for transforming growth factor beta (TGF
      beta) contributes to the fibrogenic behavior of activated lipocytes. Isolated
      lipocytes were maintained in a quiescent state by culturing the cells in
      suspension, where they displayed minimal specific binding for TGF-beta 1 and only
      a small amount of type III (betaglycan) receptor by affinity labeling. In
      contrast, lipocytes activated by growth on uncoated plastic displayed saturable
      binding of TGF-beta 1 (Kd = 28 pM, 7,730 receptors/cell), and receptors types I,
      II, and III. Binding activity in quiescent and activated cells correlated with
      responsiveness to TGF-beta 1; TGF-beta 1 induced cellular fibronectin mRNA
      expression only in activated and not quiescent cells. Despite the absence of
      binding in quiescent cells, type II receptor was detectable by immunoblot. By
      RNase protection assay, mRNAs for receptor types II and III were greater in
      quiescent than activated cells. In freshly isolated lipocytes from animals with
      liver injury caused by the administration of carbon tetrachloride, a rapid but
      transient increase in mRNA for receptor types I (approximately 3.2-fold), II
      (approximately 1.5-fold), and III (approximately 3-fold) was observed with peaks
      at 12 h for type I receptor, 1 h for type II receptor, and 6 h for type III
      receptor; mRNA induction was followed by down-regulation for all receptors. The
      modest changes in mRNAs compared with marked alterations in binding activity
      during mesenchymal cell activation suggest that TGF-beta receptors may be
      regulated in vivo in part by a post-translational mechanism.

PMID- 8144643
TI  - Induction of dolichyl-saccharide intermediate biosynthesis corresponds to
      increased long chain cis-isoprenyltransferase activity during the mitogenic
      response in mouse B cells.
AB  - There are large increases in the rates of Glc3-Man9GlcNAc2-P-P-Dol (Oligo-P-P
      Dol) biosynthesis and protein N-glycosylation during the proliferative response
      of murine B lymphocytes (B cells) to bacterial lipopolysaccharide (LPS). To learn
      more about the regulation of dolichyl-saccharide biosynthesis, the possible
      relationships between developmental changes in specific steps in dolichyl
      phosphate (Dol-P) and N-acetyl-glucosaminylpyrophosphoryldolichol (GlcNAc-P-P
      Dol) biosynthesis and the induction of Oligo-P-P-Dol biosynthesis were
      investigated. These studies describe an impressive induction of long chain cis
      isoprenyltransferase (cis-IPTase) activity, an enzyme system required for the
      chain elongation stage in de novo Dol-P synthesis, which corresponded to the
      striking increase in the rate of Oligo-P-P-Dol biosynthesis in LPS-activated B
      cells. The cellular level and specific activity of cis-IPTase increase 15-fold in
      LPS-treated cells with relatively unaltered affinity for isopentenyl
      pyrophosphate. The rates of Dol-P and Oligo-P-P-Dol synthesis increased
      substantially when cis-IPTase activity was induced, suggesting a regulatory
      relationship between the level of cis-IPTase activity and lipid intermediate
      synthesis. Distinctly different developmental patterns were observed for cis
      IPTase and HMG-CoA reductase activity, and when sterol biosynthesis was
      drastically inhibited by lovastatin, the rate of synthesis of Dol-P was slightly
      higher in the presence of the drug. Modest elevations in the cellular levels of
      dolichol kinase, Dol-P phosphatase, and UDP-GlcNAc:Dol-P N
      acetylglucosaminylphosphoryltransferase (L-G1PT) activities were also observed,
      but these changes were relatively small compared with the increases in cis-IPTase
      activity and the rates of Dol-P, Gl-cNAc-P-P-Dol, and Oligo-P-P-Dol synthesis.
      The expression of the L-G1PT gene is an early event in the developmental program
      for Oligo-P-P-Dol synthesis, but GlcNAc-P-P-Dol formation is apparently not rate
      limiting. In summary, large increases in cis-IPTase activity and the rate of Dol
      P biosynthesis appear to play a key regulatory role in the induction of Oligo-P-P
      Dol biosynthesis during the proliferative response of B cells to LPS, and the
      biosynthetic pathways for Dol-P and cholesterol are regulated independently in
      dividing B cells.

PMID- 8144644
TI  - Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter
      pylori strains.
AB  - Approximately 50% of Helicobacter pylori isolates produce a cytotoxin in vitro
      that induces vacuolation of eukaryotic cells. Screening a lambda ZapII library of
      H. pylori 60190 chromosomal fragments permitted the identification of a 3864-base
      pair (bp) open reading frame (vacA) that encoded the vacuolating cytotoxin, and a
      > or = 567-bp upstream gene that was homologous to Escherichia coli cysteinyl
      tRNA synthetase. The sequence data suggest that a 33-amino-acid leader sequence
      and a C-terminal peptide are cleaved from a 139-kDa protoxin to yield the mature
      87-kDa cytotoxin. The vacA gene product contains a C-terminal motif that is
      present in several other bacterial proteins that undergo C-terminal cleavage,
      including IgA proteases of Haemophilus influenzae and Neisseria gonorrhoeae.
      Isogenic H. pylori mutants with insertional mutation of the vacA gene lacked
      vacuolating cytotoxin activity and failed to produce the 87-kDa protein. Southern
      analysis of naturally occurring tox-H. pylori strains with vacA probes indicated
      the presence of hybridizing bands, but both Southern analysis and polymerase
      chain reaction studies suggested that the vacA sequences of tox- strains differed
      from those of tox+ strains. Sequence analysis of a 1541-bp region of polymerase
      chain reaction-amplified vacA from tox- strain 87-203 indicated 64.8% amino acid
      identity with the corresponding region from tox+ strain 60190. Thus, sequence
      divergence in vacA genes may explain the lack of functionally active cytotoxin
      production by some H. pylori isolates.

PMID- 8144645
TI  - Misfolded human chorionic gonadotropin beta subunits are secreted from
      transfected Chinese hamster ovary cells.
AB  - There are six intramolecular disulfide (S-S) bonds that form during intracellular
      folding of the human chorionic gonadotropin (hCG)-beta subunit. Site-directed
      mutagenesis of every pair of Cys residues involved in the formation of each S-S
      bond was used to examine the roles that S-S bonds play in beta subunit folding
      and secretion. Tryptic maps of secreted hCG-beta showed that only one S-S bond
      formed in all S-S bond mutants that failed to fold from the earliest detectable
      beta folding intermediate, p beta 1, into a second major intermediate, p beta 2
      (C34A-C88A, C38A-C57A or C9A-C90A mutants), whereas all 5 remaining S-S bonds
      formed in mutants when p beta 1-->p beta 2 conversion occurred (C23A-C72A, C93A
      C100A, or C26A-C110A mutants). Nonreducing SDS-polyacrylamide gel electrophoresis
      showed that beta multimers were secreted from cells expressing S-S bond mutations
      where the folding of p beta 1-->p beta 2 was blocked. However, for mutations
      where p beta 1-->p beta 2 conversion was efficient, beta monomers rather than
      multimers were secreted. For all cell lines studied, secreted hCG-beta migrated
      as monomeric beta during reducing SDS-polyacrylamide gel electrophoresis,
      indicating that hCG-beta multimers formed via intermolecular cross-linking of
      unpaired thiols. Tryptic maps of hCG-beta isolated from mutants lacking the 34-88
      bond, where > 80% turnover occurs, showed that only the 38-57 S-S bond formed.
      beta Subunits lacking the 9-90 linkage also have only S-S bond 38-57 formed, but
      < 10% turnover of C9A-C90A hCG-beta occurs. Thus, subtle conformational
      differences between partially folded or misfolded beta subunits may determine
      whether hCG-beta is degraded, or undergoes intracellular translocation and
      secretion.

PMID- 8144646
TI  - Regulation by nerve growth factor and protein phosphorylation of Na/K/2Cl
      cotransport and cell volume in PC12 cells.
AB  - PC12 cells possess a bumetanide-sensitive Na/K/2Cl cotransport system similar to
      that found in other cell types. Between 10-15% of the total 86Rb influx in these
      cells is mediated by this pathway under normal conditions. The cotransporter has
      affinities of 16.5 mM for Nao and 0.7 mM for Ko, is absolutely dependent on Clo
      and is loop diuretic inhibitable (benzmetanide > bumetanide > piretanide >
      furosemide). The cotransporter can be activated (up to 8-fold) by cell shrinkage
      or (up to 4-fold) by treatment with the protein phosphatase inhibitors okadaic
      acid (EC50 approximately 650 nM) or calyculin A (EC50 approximately 8 nM). Cell
      shrinkage is followed by a bumetanide-sensitive regulatory volume increase as
      determined in cell sizing experiments. Calyculin A rapidly elevates normal cell
      volume in a diuretic-inhibitable manner. Cotransport activity and cell volume are
      also increased by nerve growth factor (NGF) treatment. The effect of NGF on
      cotransport rate is biphasic, with an initial rapid approximately 2.5-fold
      increase followed by a prolonged plateau, and is blocked by pretreatment of the
      cells with K252a (IC50 approximately 30 nM). By contrast, agents that raise cAMP
      or phorbol esters lead to an inhibition of cotransport, indicating that the NGF
      effect is not mediated by stimulation of either cAMP-dependent protein kinase or
      protein kinase C. Long term NGF treatment (> 2 days) leads to neurite formation
      and a maintained approximately 2-fold increase in cotransport activity.
      Bumetanide treatment does not affect the ability of cells to extend neurites, nor
      is the growth rate of cells in normal medium affected by the diuretic. These
      results suggest that the cotransport system in PC12 cells is acutely regulated by
      protein phosphorylation and dephosphorylation as well as cell shrinkage and that
      cotransport activity may be up-regulated during neuronotypic differentiation.

PMID- 8144647
TI  - Isolation and characterization of a mutant dihydrofolate reductase-thymidylate
      synthase from methotrexate-resistant Leishmania cells.
AB  - The MTX-resistant Leishmania major promastigote cell line D7BR1000 displays
      extrachromosomal amplified R-region DNA, which contains the gene for
      dihydrofolate reductase-thymidylate synthase (DHFR-TS) (Garvey, E. P., and Santi,
      D. V. (1986) Science 233, 535-540). Now we report that these methotrexate (MTX)
      resistant cells also possessed a structurally altered DHFR-TS. We have performed
      the cloning, expression, and characterization of the altered DHFR-TS gene. The
      DNA sequence of the altered DHFR-TS gene revealed a single base change in
      position 158 which resulted in the substitution of a methionine in position 53 of
      DHFR for an arginine. Steady-state measurements of the purified recombinant
      enzyme indicated that the mutation did not cause significant modifications in the
      Km for DHFR or TS substrates but lowered the kcat by 4-fold. Of greater interest,
      there was a modification in the effect on MTX inhibition of DHFR. The initial
      inhibition complex appeared to have been unaffected by the alteration, but the
      subsequent slow-binding step of inhibition in the wild-type enzyme is absent in
      the altered enzyme. Consequently, the overall Ki for MTX was 30-fold greater for
      the mutant than for the wild-type enzyme. Transfection of L. major with the
      mutant DHFR-TS gene gives parasites that are capable of growing in medium
      containing 10 mM methotrexate, showing that the altered DHFR gene is in itself
      capable of conferring MTX resistance in Leishmania.

PMID- 8144648
TI  - Selenophosphate synthetase. Enzyme properties and catalytic reaction.
AB  - Selenophosphate synthetase, the product of the selD gene, produces the
      biologically active selenium donor compound, monoselenophosphate, from ATP and
      selenide. Isolation of the enzyme and characterization of some of its physical
      and catalytic properties are described. Magnesium ion and a monovalent cation,
      K+, NH4+, or Rb+, are required for catalytic activity. Polyphosphates and other
      common nucleotide triphosphates do not replace ATP as substrate. The
      stoichiometry of the catalytic reaction (Reaction 1) was established using 31P
      NMR, anaerobic molecular sieve chromatography, and radiochemical labeling
      procedures. ATP+selenide+H2O-->selenophosphate+Pi+AMP. In the absence of
      selenide, ATP is converted completely to AMP and orthophosphate upon prolonged
      incubation with elevated levels of enzyme. AMP is a competitive inhibitor of ATP,
      Ki = 170 microM, whereas selenophosphate and orthophosphate are weak inhibitors
      indicating a multistep reaction. Attempts to obtain direct evidence for a
      postulated enzyme-pyrophosphate intermediate using several experimental
      approaches are described. No exchange of [14C]AMP with ATP could be detected
      after the enzyme was freed of traces of contaminating adenylate kinase by
      chromatography on phenyl-Sepharose.

PMID- 8144649
TI  - Mutation of the two carboxyl-terminal tyrosines in the insulin receptor results
      in enhanced activation of mitogen-activated protein kinase.
AB  - Activation of mitogen-activated protein (MAP) kinase represents an important
      mechanism in hormonal regulation. To clarify the role of MAP kinase activation in
      insulin action, we compared the activation of the enzyme in Rat-1 cells
      transfected with wild-type (Hirc) and mutant insulin receptors in which the 2
      carboxyl-terminal tyrosines were substituted with phenylalanine (Y/F2).
      Expression of the Y/F2 mutant receptor enhanced the responsiveness of MAP kinase
      to insulin. Moreover, the insulin responsiveness of the activator of this enzyme,
      MAP kinase kinase, was also increased in these cells. To explore the early
      signaling events that might account for this increase in responsiveness, we
      evaluated the tyrosine phosphorylation of the insulin receptor substrate, IRS-1,
      and its subsequent association with phosphatidylinositol (PI)-3 kinase. In both
      cell types, insulin led to a dose-dependent increase in the association of
      tyrosine phosphorylated IRS-1 with the SH2 domain of the p85 regulatory subunit
      of PI-3 kinase, and also increased the amount of PI kinase activity detected in
      anti-IRS-1 immunoprecipitates. The effect of insulin was significantly greater in
      Y/F2 cells, as determined in both assays. In previous studies, cells bearing this
      receptor mutant exhibited an identical metabolic response but enhanced mitogenic
      response to insulin when compared with wild-type receptor. These data provide
      further evidence for divergence of the mitogenic and metabolic signaling pathways
      at or near the insulin receptor.

PMID- 8144650
TI  - Positively charged side chains in the insulin-like growth factor-1 C- and D
      regions determine receptor binding specificity.
AB  - Human insulin-like growth factor-1 (hIGF-1) contains seven positively charged
      residues in the A-, C-, and D-regions that are not present in similar positions
      in insulin. To determine whether these residues contribute to receptor binding
      specificity for the insulin-like growth factor-1 receptor (IGF-1R) relative to
      the insulin receptor (IR) we examined the binding of hIGF-1 analogs in which
      these residues have been replaced with either alanine or the corresponding
      residue of insulin. To improve expression and facilitate purification we employed
      insulin-like growth factor (IGF-1) analogs modified with an N-terminal 8-amino
      acid epitope. This additional epitope did not alter receptor binding specificity.
      Alanine substitution for the positively charged residues in the C- and D-regions
      of IGF-1 led to 15- and 10-fold losses, respectively, in binding potency for the
      human IGF-1R, but they increased the potency of binding to the human IR 29- and 6
      fold, respectively. In contrast, substitution of the positively charged side
      chains in the A-region with the corresponding uncharged residues of insulin had
      little effect on binding to either receptor. These data suggest that the positive
      charges in the C- and D-regions of IGF-1 contribute significantly to the binding
      preference of the IGF-1R for IGF-1. In complementary experiments using chimeric
      receptors we have also shown that the IGF-1 receptor elements required to
      discriminate in favor of the positive charges in the C- and D-regions are
      contained in the N-terminal 283 amino acids of the alpha-subunit. Insulin
      receptor elements that discriminate against these charges are within the N
      terminal 225 amino acids of its alpha-subunit.

PMID- 8144651
TI  - Intestinal absorption of peptides by coupling to bile acids.
AB  - Poor intestinal absorption of peptides greatly limits their use as drugs for the
      treatment of chronic diseases. Since bile acids are efficiently absorbed by an
      active, Na(+)-dependent transport system in the ileum of mammals, model peptides
      of different chain length were attached to the 3-position of modified 3 beta
      (omega-amino-alkoxy)-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid. These
      peptide-bile acid conjugates inhibited Na(+)-dependent [3H]taurocholate uptake
      into brush-border membrane vesicles isolated from rabbit ileum in a concentration
      dependent manner. Furthermore, photoaffinity labeling of the bile acid-binding
      proteins of M(r) 93,000 and 14,000, identified as the protein components of the
      ileal Na(+)-dependent bile acid transport system in rabbit ileum (Kramer, W.,
      Girbig, F., Gutjahr, U., Kowalewski, S., Jouvenal, K., Muller, G., Tripier, D.,
      and Wess, G. (1993) J. Biol. Chem. 268, 18035-18046) by the photoreactive
      taurocholate analogue, (3,3-azo-7 alpha, 12 alpha-dihydroxy-5 beta [7 beta, -12
      beta-3H]cholan-24-oyl)-2-aminoethanesulfonic acid, was inhibited by the peptide
      bile acid conjugates. In contrast, the parent peptides and amino acids neither
      had a significant effect on [3H]taurocholate uptake by ileal brush-border
      membrane vesicles nor on photoaffinity labeling of the ileal bile acid-binding
      membrane proteins. The inhibitory effect of peptide-bile acid conjugates on
      [3H]taurocholate transport and photoaffinity labeling of the bile acid-binding
      proteins in rabbit ileal vesicles decreased with increasing chain length of the
      attached peptide radical. By in vivo ileum perfusion in anesthetized rats an
      intestinal absorption of the bile acid conjugate S3744 of the fluorescent
      oxaprolylpeptide 4-nitrobenzo-2-oxa-1,3-diazol-beta-Ala-Phe-5-Opr-Gly (S1037) and
      secretion of the intact compound into bile could be demonstrated, whereas the
      parent peptide S1037 or its t-butylester S4404 were not absorbed. The intestinal
      absorption of S3744 showed a similar temperature dependence as [3H]taurocholate
      absorption and was inhibited by the presence of taurocholate indicating a carrier
      mediated uptake of S3744 via the ileal bile acid transporter. In conclusion,
      these results indicate that oligopeptides can be made enterally absorable by
      coupling to modified bile acid molecules making use of the specific intestinal
      absorption pathway for bile acids. This finding may be of great importance for
      the design and development of orally active peptide drugs.

PMID- 8144652
TI  - The oligosaccharide binding specificities of CD22 beta, a sialic acid-specific
      lectin of B cells.
AB  - CD22 beta is a B cell surface glycoprotein involved in cell adhesion and
      activation. We previously reported that a recombinant soluble form termed CD22
      beta Rg is capable of binding alpha 2-6 sialylated complex N-linked
      oligosaccharides purified from lymphocyte glycoprotein ligands (Powell, L. D.,
      Sgroi, D., Sjoberg, E. R., Stamenkovic, I., and Varki, A. (1993) J. Biol. Chem.
      268, 7019-7027). Here, we utilize a number of naturally and enzymatically
      sialylated oligosaccharides and sialoglycoproteins to further define its lectin
      specificity and demonstrate that the minimal structure recognized is Neu5Ac alpha
      2-6Gal beta 1-4Glc(NAc). Reduction of the glucose residue of Neu5-Ac alpha 2-6Gal
      beta 1-4Glc diminishes the interaction, while truncation of the sialic acid side
      chain by mild periodate oxidation abolishes it. Branched oligosaccharides with
      two alpha 2-6-sialyl residues bind better, regardless of whether they were
      derived from N- or O-linked oligosaccharides or from gangliosides. alpha 2-3
      Sialyl residues have no effect on binding, whereas increasing the number of alpha
      2-6-sialyl residues on multiantennary oligosaccharides progressively improves
      binding. No specific feature of the core region affects binding, although the
      spacing of the alpha 2-6-sialyl residues on tetraantennary chains appears to have
      a significant effect. Of several model sialoglycoproteins examined, fetuin and
      transferrin had an apparent affinity no greater than that observed with free
      sialylated N-linked oligosaccharides. Some subfractions of these proteins
      displayed unexpectedly weak binding, suggesting that the protein backbone can
      exert a negative effect. In contrast, a subfraction of alpha 1-acid glycoprotein
      was identified as having a substantially higher apparent affinity than free
      oligosaccharides derived from it, indicating that multiple glycosylation sites
      may increase the apparent binding affinity. Thus, CD22 beta Rg contains a lectin
      activity specific for the minimal motif Neu5Ac alpha 2-6Gal beta 1-4Glc(NAc), and
      branched, multisialylated oligosaccharides are better ligands, regardless of the
      core sequences. Intact sialoglycoproteins can also interact, although with a
      variable affinity not directly predictable from the precise structure of their
      sialylated oligosaccharides chains. These data may help to explain why certain T
      and B cell surface sialoglycoproteins with the Neu5Ac alpha 2-6Gal beta 1
      4Glc(NAc) motif are superior ligands, capable of mediating CD22 beta-mediated
      adhesion and activation events.

PMID- 8144653
TI  - Cytokine-induced beta-galactoside alpha-2,6-sialyltransferase in human
      endothelial cells mediates alpha 2,6-sialylation of adhesion molecules and CD22
      ligands.
AB  - Sialic acids decorating blood and cell surface proteins can play important roles
      in various biological processes. The inflammatory cytokines tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1, as well as bacterial lipopolysaccharide, can
      activate vascular endothelium, increasing expression of several surface
      glycoproteins. Here we show that treatment of cultured human endothelial cells
      (HEC) with TNF-alpha, interleukin-1, or lipopolysaccharide causes increased
      expression of the enzyme beta-galactoside alpha-2,6-sialytransferase (alpha 2
      6STN). TNF-alpha was most effective, inducing a 3.5-fold enhancement of cell
      associated sialytransferase activity by 72 h. In addition, activated HEC secreted
      a large portion of the induced sialyltransferase activity into the medium.
      Analysis of labeled HEC showed both a relative and an absolute increase of alpha
      2,6-linked sialic acid on N-linked oligosaccharides after TNF-alpha stimulation.
      This coincided with increased expression of endothelial glycoproteins bearing N
      linked glycans with alpha 2,6-linked sialic acid detected by the lectin Sambucus
      nigra agglutinin. The cytokine-inducible endothelial cell adhesion molecules E
      selectin, ICAM-1, and VCAM-1 are among these glycoprotein substrates for alpha 2
      6STN. These changes also correlated with a substantial increase in binding sites
      for CD22 beta, a mammalian lectin known to recognize oligosaccharides carrying
      multiple copies of alpha 2,6-linked sialic acid. Northern analysis revealed
      increased levels of mRNA encoding alpha 2-6STN. Thus, activation of endothelial
      cells during inflammatory and immunological processes may induce alpha 2-6STN,
      which can participate in sialylation of other activation-dependent molecules.

PMID- 8144654
TI  - Factor X-activating glycoprotein of Russell's viper venom. Polypeptide
      composition and characterization of the carbohydrate moieties.
AB  - There is contradictory information regarding the molecular weight and polypeptide
      chain composition of RVV-X, a glycoprotein in Russell's viper venom that is
      capable of activating factor X to Xa. We show that RVV-X is a 92,880-Da
      glycoprotein. It consists of three disulfide-linked polypeptide chains, one heavy
      chain (alpha-chain, M(r) 57,600) and two light chains (beta- and gamma-chains,
      M(r) 19,400 and 16,400, respectively). The two light chains seen on SDS
      polyacrylamide gel electrophoresis under reducing conditions are two distinct
      components of the molecule, rather than a heterogeneous mixture of a single chain
      as previously reported (Takeya, H., Nishida, S., Miyata, T., Kawada, S., Saisaka,
      Y., Morita, T., and Iwanaga, S. (1992) J. Biol. Chem. 267, 14109-14117). The
      following evidence supports this conclusion. (i) The two light chains of RVV-X
      are present in equal proportion. (ii) The estimated molecular weight of an alpha
      1 beta 1 gamma 1-structure closely matches the molecular weight determined by
      matrix-assisted laser desorption mass spectrometry. (iii) The amino acid
      compositions and NH2-terminal sequences of the beta- and gamma-chains are
      different. (iv) Although both the beta- and gamma-chains contain one N-linked
      oligosaccharide chain each, they are glycosylated differentially. RVV-X contains
      six N-linked oligosaccharides, four in the alpha-chain and one in each of the
      beta- and gamma-chains. The carbohydrate structures are different from those
      known for other snake venom glycoproteins, and they resemble closely those in
      various mammalian glycoproteins. The majority of the oligosaccharides are complex
      bi-, tri-, and tetraantennary structures, with a small proportion of
      multiantennary and high mannose-type structures. Two notable structural features
      of RVV-X oligosaccharides are as follows. (i) Sialic acid residues are linked to
      beta-galactosyl residues solely by alpha 2,3-linkages, and (ii) bisecting N
      acetylglucosamine residues are present in the majority of the oligosaccharides.

PMID- 8144655
TI  - Structure and expression of the human slow twitch skeletal muscle troponin I
      gene.
AB  - The contractile protein troponin I is encoded by a multigene family whose members
      are expressed differentially in various classes of muscle fibers. In vertebrates,
      the "slow" isoform of troponin I is expressed during early heart and skeletal
      muscle development but is restricted to slow twitch skeletal muscle in the adult.
      This diverse expression pattern offers an opportunity to study the regulation of
      a single gene within different developmental contexts. To initiate such studies,
      we have cloned the gene encoding the human slow twitch skeletal muscle isoform of
      troponin I and have identified 5'-flanking sequences required for its expression
      in skeletal muscle cells. The slow troponin I gene spans 12.5 kilobases and is
      divided into nine exons. In contrast to many muscle-specific genes, the troponin
      I promoter does not contain consensus CCAAT or TATA elements. Moreover, the
      sequence from -9 to +11 resembles an "initiator element" previously shown to
      direct transcription of some tissue-specific genes lacking TATA boxes (Smale, S.
      T., and Baltimore, D. (1989) Cell 57, 103-113; Brand, N. J., Petkovich, M., and
      Chambon, P. (1990) Nucleic Acids Res. 18, 6799-6806; Weis, L., and Reinberg, D.
      (1992) FASEB J. 6, 3300-3309). A transcriptional fusion construct, comprising 4.2
      kilobases of troponin I 5'-flanking DNA linked to the bacterial chloramphenicol
      acetyl-transferase gene, exhibited cell type-specific and developmentally
      regulated expression. A muscle-specific enhancer regulated slow troponin I
      promoter activity.

PMID- 8144656
TI  - GATA-type zinc finger motif-containing sequences and chorion gene transcription
      factors of the silkworm Bombyx mori.
AB  - To characterize a DNA-binding protein, BCFI, which regulates the expression of
      silkmoth chorion genes through binding to gene promoter elements identical to
      those recognized by the GATA family of transcription factors, we have carried out
      polymerase chain reaction amplifications of Bombyx mori genomic DNA using
      degenerate primers derived from the conserved DNA binding domain of mammalian
      GATA factors. Two single copy genes, BmGATA alpha and BmGATA beta, were
      identified, which encode sequences containing GATA-type zinc finger motifs. The
      BmGATA beta gene is expressed in follicular and Bm5 tissue culture cells, the two
      cell types that contain BCFI. No BmGATA alpha gene transcripts were detectable in
      the tissues that were tested. Upon overexpression in Escherichia coli, a peptide
      encompassing the BmGATA beta zinc finger motif was able to bind specifically to
      the BCFI recognition motif of the chorion gene promoters. A polyclonal antibody
      directed against the zinc finger domain of BmGATA beta was also used in gel
      retardation assays to confirm that factor BCFI is indeed encoded by the BmGATA
      beta gene. Conceptual translation of a complete cDNA clone encoding the BmGATA
      beta protein revealed that this protein has a size similar to that of an
      immunoreactive protein, presumably BCFI, which is present in follicular cell
      extracts.

PMID- 8144657
TI  - Intermediate filament-like network formed in vitro by a bacterial coiled coil
      protein.
AB  - The TlpA protein encoded by the virulence plasmid of Salmonella enterica is an
      alpha-helical 371-amino acid protein possessing characteristics similar to
      eukaryotic coiled coil proteins (Koski, P., Saarilahti, H., Sukupolvi, S., Taira,
      S., Rikkonen, P., Osterlund, K., Hurme, R., and Rhen, M. (1992) J. Biol. Chem.
      267, 12258-12265). In this paper we have investigated inter- and intramolecular
      associations and the morphology of structures formed by TlpA. Dynamics and
      temperature stability of TlpA dimers were studied by examining the feasibility
      and conditions in which TlpA would form an artificial heterodimer with its
      truncated derivative. Formation of heterodimers, bridged by Cu(2+)-catalyzed air
      oxidation of adjacent Cys residues, showed that TlpA dimers are dynamic chain
      exchanging structures at 37 degrees C, whereas they were nonexchanging at room
      temperature or on ice. Chemical cross-linking suggested higher order interaction
      between TlpA dimers. Electron microscopy studies revealed two levels of TlpA
      organization in vitro: thin filaments and rods, 2-5 nm in diameter, and a higher
      ordered filament network consisting of tonofilament-like formations with a
      diameter of 8-15 nm. Electron microscopy of thin-sectioned Escherichia coli over
      producing TlpA showed an extraordinary intracellular assembly of proteinacious
      lamellae with a striated appearance and a 38-nm periodicity. This study describes
      for the first time a bacterial protein capable of organizing itself into an
      ordered and suspectedly dynamic intermediate filament-like architecture.

PMID- 8144658
TI  - Cloning and expression of a novel acidic calponin isoform from rat aortic
      vascular smooth muscle.
AB  - The actin-binding protein calponin has been implicated in the regulation of
      smooth muscle contraction. We have isolated cDNA clones encoding a novel acidic
      calponin isoform from rat aortic vascular smooth muscle cells. The initial 273
      residues of the deduced 330 amino acid polypeptide (M(r) 36,377) are highly
      homologous to basic smooth muscle calponin isoforms, but the remaining 57
      residues at the carboxyl terminus comprise a unique and strongly acidic domain.
      The sequence of the acidic domain shows high homology (93.3% identity) to the
      partial sequence of HUMXT01244, an unidentified human hippocampal gene product
      (Adams, M., Dubnick, M., Kerlavgne, A. R., Moreno, R., Kelly, J. M., Utterback,
      T. R., Nagle, J. W., Fields, C., and Venter, J. C. (1992) Nature 355, 632-634).
      Transcripts encoding acidic calponin are expressed in cultured rat aortic
      vascular smooth muscle cells and in non-muscle and smooth muscle tissues of adult
      rat. Based on its calculated M(r) and the tissue distribution of its expression,
      acidic calponin is an excellent candidate for a previously detected non-muscle
      calponin homolog (Takeuchi, K., Takahashi, K., Abe, M., Nishida, W., Hiwada, K.,
      Nabeya, T., and Maruyama, K. (1991) J. Biochem. (Tokyo) 109, 311-316). Like basic
      calponin isoforms, acidic calponin synthesized in a bacterial expression system
      bound F-actin. However, unlike basic calponin, the acidic isoform did not
      interact with Ca2+/calmodulin, indicating a functional distinction between the
      muscle and non-muscle forms.

PMID- 8144659
TI  - In vitro characterization of nonpeptide irreversible inhibitors of HIV proteases.
AB  - The irreversible inhibition of human immunodeficiency virus type 1 (HIV-1) and
      type 2 (HIV-2) proteases by 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) and eight
      haloperidol derivatives has been studied. EPNP specifically inhibits HIV-1 and
      HIV-2 proteases with a stoichiometry of one EPNP molecule/dimeric enzyme. The
      site of modification of HIV-2 protease by EPNP has been unambiguously identified
      as Asp-25 using high performance tandem mass spectrometry. The haloperidol
      derivatives assayed consist of epoxides, ynones, and alpha,beta-unsaturated
      ketones. The Kinact values for these haloperidol derivatives range from 10.7 to
      521 microM for HIV-1 protease and from 8.6 to 283 microM for the HIV-2 enzyme,
      being in some cases approximately 1000-fold more potent irreverisble inhibitors
      of HIV proteases than EPNP. This potency results from the haloperidol character
      of the compounds and the chemical reactivity of the groups capable of forming a
      covalent bond with the enzyme. Covalent modification of HIV-2 protease by a
      radiolabeled epoxide derivative of haloperidol, UCSF 84, is prevented by EPNP and
      the peptidomimetic transition state analog U-85548. In similar experiments,
      incorporation of UCSF 84 into HIV-1 protease is partially prevented by these
      active-site inhibitors. In contrast, a mutant HIV-1 protease, HIV-1 PR C95M, in
      which Cys-95 has been replaced by Met, is labeled 50% less than HIV-1 protease
      and is fully protected by EPNP and U-85548. These results indicate the presence
      of 2 reactive residues in HIV-1 protease: Cys-95 and another located in the
      active site of the enzyme. The alpha,beta-unsaturated ketone derivative of
      haloperidol, UCSF 191, which is stable over a broad pH range, was used to study
      the pH profile of inactivation of HIV-1 and HIV-2 proteases. Comparison of the
      profiles of inactivation of wild-type HIV-1 protease, HIV-1 PR C95M, and HIV-1 PR
      C67L as well as HIV-2 protease (which has no cysteine residues) reveals the
      contribution of Cys-95 to the reactivity of these irreversible inhibitors. The
      inhibitors UCSF 70, UCSF 84, UCSF 115, UCSF 142, and UCSF 191 reduce p55gag
      polyprotein processing when assayed in a mammalian cell line that produces HIV-1
      viral particles lacking the envelope.

PMID- 8144660
TI  - Clostridium difficile toxin B acts on the GTP-binding protein Rho.
AB  - Clostridium difficile toxin B exhibits cytotoxic activity that is characterized
      by the disruption of the microfilamental cytoskeleton. Here we studied whether
      the GTP-binding Rho protein, which reportedly participates in the regulation of
      the actin cytoskeleton, is involved in the toxin action. Toxin B treatment of
      Chinese hamster ovary cells reveals a time- and concentration-dependent decrease
      in the ADP-ribosylation of Rho by Clostridium botulinum C3 exoenzyme in the cell
      lysate. Disruption of the microfilament system induced by C. botulinum C2 toxin
      or cytochalasin D does not cause impaired ADP-ribosylation of Rho. Toxin B
      exhibits its effects on Rho not only in intact cells but also when added to cell
      lysates. Besides endogenous Rho, RhoA-glutathione S-transferase (Rho-GST) fusion
      protein added to cell lysate showed decreased ADP-ribosylation after toxin B
      treatment. Immunoblot analysis reveals identical amounts of Rho-GST and no change
      in molecular mass after toxin B treatment compared with controls. ADP
      ribosylation of Rho-GST purified from toxin B-treated cell lysate is inhibited,
      indicating a modification of Rho itself. Finally, transfection of rhoA DNA under
      the control of a strong promoter into cells protects them from the activity of
      toxin B. Altogether, the data indicate that C. difficile toxin B acts directly or
      indirectly on Rho proteins to inhibit ADP-ribosylation and suggest that the
      cytotoxic effect of toxin B involves Rho.

PMID- 8144661
TI  - High affinity interaction of dipteran high mobility group (HMG) proteins 1 with
      DNA is modulated by COOH-terminal regions flanking the HMG box domain.
AB  - The cells of the dipteran insects Chironomus and Drosophila contain high mobility
      group (HMG) 1 proteins that are homologous to the HMG1 protein of mammals but
      comprise one instead of two DNA-binding HMG boxes. Mobility shift assays have
      revealed that Chironomus cHMG1a and cHMG1b bind double strand and four-way
      junction DNA in a similar way at apparent dissociation constants in the range of
      7.5-20 x 10(-9) M. Both proteins are monomeric and highly asymmetric molecules in
      solution. cHMG1a and cHMG1b exhibit Stokes' radii of 2.4 and 2.3 nm,
      respectively, and both show a frictional ratio of 1.5. Despite these similarities
      in their hydrodynamic properties, the binding site of cHMG1a on DNA is
      approximately 1.5 of the size found for the cHMG1b. Enzymatically and chemically
      prepared peptides of cHMG1a as well as bacterially expressed cHMG1a with terminal
      deletions and point substitutions showed that sequences flanking the folded
      domain that constitutes the HMG box are essential for the interaction of the HMG
      box with DNA. In particular, changes in the number of positive and negative
      charges, respectively, within basic and acidic domains modulated the DNA binding
      affinity of the cHMG1a protein. The alteration of fluorescence of the Trp
      residues suggest that this modulation is due to interaction of the acidic domain
      with the positively charged HMG box.

PMID- 8144662
TI  - Shc is the predominant signaling molecule coupling insulin receptors to
      activation of guanine nucleotide releasing factor and p21ras-GTP formation.
AB  - Insulin stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS
      1) and She in Rat1 fibroblasts overexpressing wild type insulin receptors. We
      investigated the relative role of IRS-1 and She in insulin activation of guanine
      nucleotide releasing factor (GNRF) and p21ras-GTP formation. The time course of
      insulin-stimulated tyrosine phosphorylation of IRS-1 was rapid, whereas Shc
      phosphorylation was relatively slow. Growth factor receptor bound protein-2
      (Grb2) associated with IRS-1 rapidly and gradually dissociated after 5 min,
      whereas Grb2 association with Shc was slower and reached a maximum at 10 min
      after insulin stimulation. Thus, the kinetics of Grb2 association with IRS-1 and
      She corresponded closely to the time course of tyrosine phosphorylation of IRS-1
      and Shc, respectively. Importantly, 3-13-fold more Grb2 was associated with Shc
      than with IRS-1. In addition, the kinetics of insulin-stimulated GNRF activity
      and p21ras-GTP formation corresponded more closely to the time course of Shc
      phosphorylation than to the kinetics of IRS-1 phosphorylation. Furthermore,
      immunoprecipitation of Shc proteins from cell lysates of insulin-stimulated cells
      removed 67% of the GNRF activity, whereas precipitation of IRS-1 had a negligible
      effect on GNRF activity. Thus, although both IRS-1 and Shc associate with Grb2,
      the current results indicate that Shc plays a more important role than IRS-1 in
      insulin stimulation of GNRF activity and subsequent p21ras-GTP formation.

PMID- 8144663
TI  - Cytokines that associate with the signal transducer gp130 activate the interferon
      induced transcription factor p91 by tyrosine phosphorylation.
AB  - Interleukin-6, leukemia inhibitory factor, and oncostatin M exert a broad range
      of similar biological activities through association of their receptors with the
      signal-transducing component gp130. Although it is known that these cytokines
      trigger rapid tyrosine phosphorylation of a common set of cellular proteins as
      well as induction of several of the same early response genes, the mechanisms by
      which these genes are activated is not well understood. In this report, we show
      that interleukin-6, leukemia inhibitory factor, and oncostatin M stimulate the
      assembly of protein complexes that recognize conserved sequences within the
      enhancers of two genes (interferon regulatory factor 1 and Fc gamma receptor type
      I) that are rapidly activated by these cytokines. These enhancers are known to be
      required for transcriptional induction of these genes by interferon-gamma.
      Assembly of the DNA-binding protein complexes occurs within minutes after ligand
      addition and depends upon tyrosine phosphorylation. These complexes contain the
      p91 transcription factor, which is tyrosine-phosphorylated in response to these
      cytokines. An additional tyrosine-phosphorylated protein of 93 kDa can be
      coimmunoprecipitated with antibodies against p91. These findings further expand
      the network of cytokines known to activate p91 and, in addition, support the
      concept that sets of tyrosine-phosphorylated proteins may be responsible for the
      cytokine-regulated expression of early response genes.

PMID- 8144664
TI  - GTP hydrolysis by ADP-ribosylation factor is dependent on both an ADP
      ribosylation factor GTPase-activating protein and acid phospholipids.
AB  - ADP-ribosylation factor (ARF) is a 21-kDa GTP binding protein that regulates
      eukaryotic membrane traffic. Both the binding and hydrolysis of GTP by ARF have
      been shown to be necessary for this function. However, purified mammalian ARF
      lacks intrinsic GTPase activity (< 0.0015 min-1). We document the presence, in
      bovine brain extracts, of a protein with the predicted properties for an ARF
      GTPase-activating protein (ARF GAP). This activity was highly dependent on
      phospholipids. An acid phospholipid fraction from bovine brain (containing
      primarily phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4
      phosphate, phosphatidylinositol, and phosphatidylserine) had no effect on
      intrinsic GTPase activity of purified ARF but increased the ARF GAP activity of
      bovine brain homogenates about 8-fold. This dependence on acid phospholipids was
      retained after > 100-fold purification of ARF GAP, making it, likely, an inherent
      property of this reaction. PIP2 alone stimulated ARF GAP activity up to 30-fold
      with a half-maximal effect at 100-300 microM but had no effect on the GTPase rate
      of ARF alone. Phosphatidylinositol 4-phosphate was also active but had only 50%
      of the maximal effect and twice the EC50 of PIP2. Phosphatidylserine,
      phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, and
      diacylglycerol either alone or in the presence of ARF GAP do not stimulate ARF
      GTPase activity. ARF proteins have been identified recently as regulators of
      phospholipase D. The product of the phospholipase D reaction, phosphatidic acid,
      stimulated ARF GAP approximately 5-fold and reduced the PIP2 concentration needed
      for GAP stimulation about 6-fold. The substrate of phospholipase D,
      phosphatidylcholine, inhibited ARF GAP activity, but this inhibition seen with
      phosphatidylcholine was partially reversed by phosphatidic acid. A feedback loop
      for the coordinate regulation of phospholipase D and ARF activities is proposed.

PMID- 8144665
TI  - A mutational study of the C-terminal zinc-finger motif of the Escherichia coli
      UvrA protein.
AB  - The cysteine 763 residue in the C-terminal zinc-finger region of Escherichia coli
      UvrA protein was subjected to random mutagenesis, and the results suggested that
      the UvrA mutants with a small amino acid (Ser, Ala, or Gly) substituting for the
      cysteine 763 were almost as active as the wild-type in supporting nucleotide
      excision repair, but its replacement with a large, bulky amino acid (Tyr, Trp, or
      Phe) rendered the mutants inactive. The C763F mutant UvrA protein was purified
      for further characterization, and it was found this mutant UvrA protein lost its
      DNA binding (single-stranded or double-stranded DNA) activity and those other
      activities dependent on DNA binding, such as formation of damage-specific UvrA2B
      complexes and the supercoiling reaction. However, this mutant protein retained
      vigorous ATPase activity and was capable of negatively complementing the wild
      type UvrA in JM109 strain. The purified C763F mutant UvrA protein contains a
      single zinc ion/molecule, half that of the wild-type. It appears that the C763F
      mutation destabilizes the zinc-anchored structure in the C-terminal zinc finger
      region, and as a result, the C763F mutant UvrA protein lost its ability to bind
      DNA.

PMID- 8144666
TI  - Membrane cofactor protein (CD46) of complement. Processing differences related to
      alternatively spliced cytoplasmic domains.
AB  - Membrane cofactor protein (MCP, CD46), a widely distributed regulatory protein,
      inhibits complement activation on host cells and serves as a measles virus
      receptor. Most cells express four isoforms (with one of two cytoplasmic tails,
      CYT-1 or CYT-2). Previously, we noted that MCP precursors had variable
      intracellular processing. Therefore, we characterized the intracellular transport
      of individual MCP isoforms. Transfectants were used for pulse-chase analyses. MCP
      isoforms bearing CYT-1 chased into their mature, surface forms with a half-life
      (t1/2) of 10-13 min while those with CYT-2 required 35-40 min. The precursor of a
      tail-less mutant possessed a t1/2 of 160-165 min. Chimeras were constructed that
      added both tails in opposite orientation onto the isoform (i.e. CYT 1 + 2 or CYT
      2 + 1). Chimera 1 + 2 precursor processed with a t1/2 of 35-37 min, similar to
      CYT-2. Chimera 2 + 1 had a t1/2 of 15-19 min, more closely resembling CYT-1.
      Thus, in both cases the carboxyl-terminal tail controlled the processing rate.
      Deletions were made in the beginning, middle, and carboxyl terminus of CYT-1.
      Deletion of the first or middle six amino acids had no effect on the processing
      rate. However, deletion of the terminal tetrapeptide (FTSL) slowed the rate to 30
      32 min, suggesting that this sequence facilitates exit from the endoplasmic
      reticulum.

PMID- 8144667
TI  - Evidence that the cation occlusion domain of Na/K-ATPase consists of a complex of
      membrane-spanning segments. Analysis of limit membrane-embedded tryptic
      fragments.
AB  - Digestion of renal Na/K-ATPase with trypsin, in the presence of rubidium and
      absence of calcium ions, produces so-called "19-kDa membranes," containing a C
      terminal 19-kDa and smaller fragments (8-12 kDa) of the alpha chain, and a beta
      chain either intact or split into two fragments (Karlish, S. J. D., Goldshleger,
      R., and Stein, W.D. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 4566-4570). Cation
      occlusion is intact. The cation sites are thought to be located within trans
      membrane segments, but the identity and number of segments involved is unknown.
      Analysis of Ca(2+)-induced sensitization of 19-kDa membranes to proteolysis, and
      characterization of the limit membrane-embedded fragments, has provided some
      insight into this question. Calcium ions have been shown to compete with two
      rubidium ions for occlusion sites on 19-kDa membranes, with a high affinity (KD
      approximately 2.8 microM, pH 7.5, 20 degrees C). The kinetics of displacement of
      rubidium by calcium ions indicate that competition is direct and is not an
      allosteric antagonism. At 37 degrees C, reversible displacement of rubidium ions
      by calcium ions is followed by an irreversible thermal inactivation of rubidium
      occlusion. Calcium ions partially protect rubidium occlusion sites against
      modification by the carboxyl reagent, N,N'-dicyclohexylcarbodiimide. We propose
      that calcium ions, like rubidium ions, recognize carboxyl groups at the entrance
      to the cation sites, but the calcium ions do not become occluded and thus fail to
      protect 19-kDa membranes against further proteolysis or thermal inactivation.
      Upon displacement of occluded rubidium, trypsin digests the Ca(2+)-bound and
      thermally inactivated 19-kDa membranes, and all of the membrane-embedded
      fragments are truncated or are split in these conditions. A related finding is
      that the C-terminal sequence of the 19-kDa fragment (and alpha chain), E-T-Y-Y,
      is digested by carboxypeptidase Y only when the rubidium occlusion is
      inactivated. Identification of the limit tryptic fragments indicates that
      polypeptide loops and the C-terminal tail of the 19-kDa fragment, N and C termini
      of the smaller fragments of the alpha chain, and both N and C termini of a 16-kDa
      fragment of the beta chain are split by proteolytic enzymes upon displacement of
      occluded rubidium.4+ We conclude that all fragments of 19-kDa membranes form a
      complex, which is stabilized and protected against proteolytic enzymes upon
      occlusion of rubidium ions, and which relaxes upon displacement of occluded
      rubidium. The cation occlusion "cage" presumably consists of litigating groups
      from several trans-membrane segments.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8144668
TI  - Remodeling of the transmembrane segment in human glycophorin by aberrant RNA
      splicing.
AB  - This paper describes the identification in S-s-U-erythrocytes of a novel
      glycophorin (GP), He(P2), with structural variations in both its extracellular
      and transmembrane domains. In the exon II-intron 2 region, a sequence transfer
      from GPA to GPB, probably via the mechanism of gene conversion, was associated
      with the induction of multiple untemplated nucleotide replacements. These changes
      defined the sequence for the He epitope while concomitantly abolishing GPB
      associated N antigenicity. Moreover, the GPHe(P2) gene carries two splice site
      mutations that coordinately affect the processing of exon V coding for the
      transmembrane segment. The C-->G transversion at the 3' end of exon V created a
      cryptic acceptor splice site, whereas the G-->T transversion at the +5 position
      of intron 5 altered the consensus of the donor splice site. Transcript sequencing
      revealed that neither site was utilized in the splicing of GPHe(P2) pre-mRNA.
      Rather, complete skipping of exon V and subsequent joining of exon IV to exon VI
      caused a shift in the open reading frame, which remodeled GPHe(P2) with an
      elongated new hydrophobic sequence for membrane anchoring. As a result, GPHe(P2)
      does not display the S and U epitopes although it still contains an intact linear
      sequence for the two antigens. These findings illustrate how exon and intron
      sequences concertedly determine the specificity of in vivo splice site selection.
      In addition, they pinpoint the conformational dependence of the S, s, and U
      antigens and the importance of the hinge region for their presentation.

PMID- 8144669
TI  - Reciprocal interactions between protein kinase C and components of the NADPH
      oxidase complex may regulate superoxide production by neutrophils stimulated with
      a phorbol ester.
AB  - The 47-kDa subunit of the NADPH oxidase system (p47-phox) of neutrophils
      undergoes an association with proteins in the Triton X-100-insoluble fraction
      upon stimulation of the cells with 4 beta-phorbol 12-myristate 13-acetate. This
      fraction contains the assembled oxidase that catalyzes the generation of
      superoxide by stimulated cells. In this paper, we report that the addition of an
      inhibitor of protein kinases (1-(5-isoquinolinylsulfonyl-2-methylpiperazine) to
      neutrophils that are already stimulated results in the dissociation of p47-phox
      from this fraction. Antagonists of type 1 and 2A protein phosphatases (calyculin
      A, okadaic acid) prevented this phenomenon. In contrast, norokadanone, an
      inactive analog of okadaic acid, did not affect this response. These observations
      are correlated with previous studies on the phosphorylation of p47-phox and
      superoxide release. In addition, we show that protein kinase C (PKC) also
      undergoes an extensive redistribution to the Triton X-100-insoluble fraction in 4
      beta-phorbol 12-myristate 13-acetate-stimulated cells, the extent of which is
      diminished significantly in neutrophils from chronic granulomatous disease
      patients who lack either p47-phox or cytochrome b558. These studies strongly
      indicate that PKC and type 1 and/or 2A protein phosphatases are involved in a
      continuous phosphorylation reaction that maintains the oxidase in the
      assembled/active state. Moreover, components of the oxidase may target and
      facilitate the translocation of PKC to a cellular site in close apposition to the
      oxidase.

PMID- 8144670
TI  - A novel transcriptional suppressor located within a downstream intron of the BCR
      gene.
AB  - A reciprocal translocation between chromosomes 9 and 22 creates the Philadelphia
      (Ph1) chromosome in chronic myelogenous leukemia. This translocation results in
      the fusion of the ABL and the BCR genes to form a BCR/ABL fusion gene, the
      product of which has a greatly increased protein tyrosine kinase activity in
      comparison with the normal ABL protein. The chromosome 22 translocation
      breakpoints are concentrated within a 5.8-kilobase region named the major break
      point cluster region (Mbcr). Gel mobility shift and DNase I footprinting assays
      have defined binding sites for three proteins, BIF 1-3 (BCR intron factors 1-3),
      lying within a 427-base pair fragment of the Mbcr. This 427-base pair fragment
      functions as a transcriptional silencer with both the BCR as well as a
      heterologous promoter. The silencing is position- and orientation-independent.
      The transcriptional effects are greatest in chronic myelogenous leukemia cells,
      decreased in HeLa and B-cells, and absent in T-lymphocytes. Gel mobility shift
      assays show a corresponding difference in pattern when the T-lymphocyte nuclear
      extract is compared with other cell lines. The Mbcr appears to contain a novel
      group of transcriptional silencers that share a common binding motif with a
      recently described suppressor in the mouse Adh-1 gene.

PMID- 8144671
TI  - Evidence that an approximately 50-kDa mammalian plasma membrane protein with
      receptor-like properties mediates the amphiphilicity of specifically bound
      Clostridium perfringens enterotoxin.
AB  - Previous studies suggest that Clostridium perfringens enterotoxin (CPE) inserts
      into mammalian membranes. Using Triton X-114 phase separation analysis and charge
      shift electrophoresis, this study demonstrates that CPE exhibits the
      amphiphilicity required for membrane insertion, but this behavior develops only
      after exposure of CPE to membranes. This effect does not require proteolytic or
      covalent CPE modifications or formation of a previously reported 160-kDa CPE
      containing complex. A novel 90-kDa CPE-containing complex with amphiphilic
      properties was detected in intestinal brush-border membranes and in CPE
      sensitive, but not CPE-insensitive, cell lines using nondenaturing Triton X-100
      electrophoresis. Immunoprecipitation analysis suggested that the 90-kDa complex
      is composed of CPE and a 45-50-kDa membrane protein. Since the 90-kDa complex is
      formed only in cells that bind and respond to CPE, these results are consistent
      with the 45-50-kDa protein mediating CPE amphiphilicity and serving as a
      functional CPE receptor. A four-step model for CPE action is proposed. 1) CPE
      binds to the 45-50-kDa protein to form a 90-kDa complex. 2) The 90-kDa complex
      undergoes some physical change corresponding to insertion or a conformational
      change. 3) The 90-kDa complex and a 70-kDa membrane protein interact to form a
      160-kDa complex. 4) Formation of the 160-kDa complex leads to permeability
      alterations.

PMID- 8144672
TI  - Ranalexin. A novel antimicrobial peptide from bullfrog (Rana catesbeiana) skin,
      structurally related to the bacterial antibiotic, polymyxin.
AB  - Antimicrobial peptides comprise a diverse class of molecules used in host defense
      by plants, insects, and animals. In this study we have isolated a novel
      antimicrobial peptide from the skin of the bullfrog, Rana catesbeiana. This 20
      amino acid peptide, which we have termed Ranalexin, has the amino acid sequence:
      NH2-Phe-Leu-Gly-Gly-Leu-Ile-Lys-Ile-Val-Pro-Ala-Met-Ile-Cys-Ala-Val-Thr- Lys-Lys 
      Cys-COOH, and it contains a single intramolecular disulfide bond which forms a
      heptapeptide ring within the molecule. Structurally, Ranalexin resembles the
      bacterial antibiotic, polymyxin, which contains a similar heptapeptide ring. We
      have also cloned the cDNA for Ranalexin from a metamorphic R. catesbeiana tadpole
      cDNA library. Based on the cDNA sequence, it appears that Ranalexin is initially
      synthesized as a propeptide with a putative signal sequence and an acidic amino
      acid-rich region at its amino-terminal end. Interestingly, the putative signal
      sequence of the Ranalexin cDNA is strikingly similar to the signal sequence of
      opioid peptide precursors isolated from the skin of the South American frogs
      Phyllomedusa sauvagei and Phyllomedusa bicolor. Northern blot analysis and in
      situ hybridization experiments demonstrated that Ranalexin mRNA is first
      expressed in R. catesbeiana skin at metamorphosis and continues to be expressed
      into adulthood.

PMID- 8144673
TI  - An altered specificity mutation in the lambda repressor induces global
      reorganization of the protein-DNA interface.
AB  - The lambda repressor exhibits structural characteristics of lock and key
      complementary through the helix-turn-helix motif, and of induced fit by virtue of
      DNA-dependent folding of the N-terminal arm. In both cases, molecular recognition
      is mediated by direct contacts between amino acids and DNA bases. The extent to
      which such contacts function as discrete elements in a protein-DNA recognition
      code is not known. Because of the relevance of protein recognition to the broader
      issue of protein design, and because the lambda system serves as a prototype for
      gene regulation, we have employed laser Raman and 1H NMR spectroscopy to compare
      free and operator-bound structures of lambda repressor variants which are known
      to exhibit altered DNA-binding specificities. Experimental design is based upon a
      previous biochemical study of mutations in the repressor N-terminal arm (K4Q) and
      helix-turn-helix motif (G48S) (Nelson, H. C. M., and Sauer, R. T. (1986) J. Mol.
      Biol. 192, 27-38). These mutations, which were originally isolated by loss of
      function (K4Q) and second-site reversion (G48S), are of particular interest in
      light of their complex effects on sequence specificity at multiple positions in
      the operator site (Benson, N., Adams, C., and Youderian, P. (1992) Genetics 130,
      17-26). Laser Raman and 1H NMR spectra of repressor variants carrying one (G48S)
      or two mutations (K4Q/G48S) are similar to those of the native wild type
      repressor and are in accord with the x-ray crystal structure. Remarkably,
      however, the complexes of wild type and mutant repressors exhibit extensive
      differences both in the global DNA structure and in the environments of key
      functional groups along the major groove. By demonstrating that single amino acid
      substitutions can induce global reorganization of a protein-DNA interface, the
      present results establish that repressor-operator recognition in solution cannot
      be explained in terms of a simple recognition code.

PMID- 8144674
TI  - Specificity of coenzyme binding in thiamin diphosphate-dependent enzymes. Crystal
      structures of yeast transketolase in complex with analogs of thiamin diphosphate.
AB  - The three-dimensional structures of complexes of yeast apotransketolase with the
      coenzyme analogs 6'-methyl, N1'-pyridyl, and N3'-pyridyl thiamin diphosphate,
      respectively, were determined with protein crystallographic methods. All three
      coenzyme analogs bind to the enzyme in a fashion highly similar to the cofactor
      thiamin diphosphate. Thus, either one of the hydrogen bonds of the pyrimidine
      ring nitrogens to the protein is sufficient for proper binding and positioning of
      the cofactor. The lack of catalytic activity of the N3'-pyridyl analog is not due
      to incorrect orientation of the pyrimidine ring, but results from the absence of
      the hydrogen bond between the N1' nitrogen atom and the conserved residue Glu418.
      The structure analysis provides further evidence for the importance of this
      conserved interaction for enzymatic thiamin catalysis.

PMID- 8144675
TI  - The crystal structure of succinyl-CoA synthetase from Escherichia coli at 2.5-A
      resolution.
AB  - The x-ray crystal structure of succinyl-CoA synthetase (SCS) from Escherichia
      coli has been determined by the method of multiple isomorphous replacement to a
      resolution of 2.5 A. Crystals of SCS are tetragonal with a space group of P4(3)22
      and unit cell dimensions of a = b = 98.47 A and c = 400.6 A. One molecule of SCS
      (142 kDa) is contained in the asymmetric unit. The current model has been refined
      to a conventional R factor of 21.6% with root mean square deviations from ideal
      stereochemistry of 0.022 A for bond lengths and 3.25 degrees for bond angles. The
      quaternary organization of the E. coli enzyme is an alpha 2 beta 2
      heterotetramer. In this tetramer, the alpha-subunits interact only with the beta
      subunits, whereas the beta-subunits interact to form the dimer of alpha beta
      dimers. The two active site pockets are located at regions of contact between
      alpha- and beta-subunits. One molecule of coenzyme A is bound to each alpha
      subunit at a typical nucleotide-binding motif, and His-246 of each alpha-subunit
      is phosphorylated. This phosphohistidine, a catalytic intermediate, is stabilized
      by two helix dipoles (the "power" helices), one from each of the two subunit
      types. A short segment of the beta-subunit from one alpha beta-dimer is in close
      proximity to the CoA-binding site of the other alpha beta-dimer, providing a
      possible rationale for the overall tetrameric structure.

PMID- 8144676
TI  - Structure of the gene encoding the alpha subunit of the human granulocyte
      macrophage colony stimulating factor receptor. Implications for the evolution of
      the cytokine receptor superfamily.
AB  - The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is
      composed of at least two subunits, alpha and beta. In addition to the conserved
      cysteine residues and a "WSxWS" motif, the extracellular segments of both
      subunits have domains that are structurally related to a fibronectin type III
      domain. This structure is conserved in all members of the cytokine receptor
      superfamily. We isolated and characterized genomic DNA clones containing the
      entire coding sequences of the alpha subunit of the human GM-CSF receptor (hGMR
      alpha). The gene spans approximately 44 kilobases and has 13 exons. The major
      transcription initiation site was determined to be 195 base pairs upstream of the
      translation initiation site. The putative promoter region lacks a typical TATA
      motif and an Sp1 binding site, but contains a purine-rich stretch about 30 base
      pairs upstream of the transcription initiation site. This stretch is also found
      in the human interleukin 2 receptor gamma subunit and granulocyte colony
      stimulating factor receptor genes. We compared the exon-intron organization of
      the hGMR alpha gene with other members of the cytokine receptor superfamily and
      found the genomic organizations to be remarkably well conserved. On the basis of
      these observations, we propose a model for evolution of this gene family.

PMID- 8144677
TI  - Reconstitution of complete SV40 DNA replication with purified replication
      factors.
AB  - The identification and purification of human cell proteins required for the
      production of form I DNA following DNA replication from the simian virus 40
      (SV40) origin is described. Using these proteins, complete SV40 DNA replication
      was reconstituted with only purified DNA replication factors: SV40 large tumor
      antigen (TAg), replication protein A (RPA), DNA topoisomerases I and II, DNA
      polymerase alpha-primase, replication factor C (RFC), the proliferating cell
      nuclear antigen (PCNA), DNA polymerase delta, maturation factor 1 (MF1), and DNA
      ligase I. MF1, a 5' to 3' exonuclease and DNA ligase I were both identified as
      essential components for production of covalently closed circular relaxed (form
      I) DNA. MF1 is probably the same exonuclease previously shown by others to
      function during DNA synthesis on artificial DNA templates or in conjunction with
      DNA polymerase alpha from the SV40 origin. Combined with these previous studies,
      our results suggest that MF1 functions to remove an RNA primer attached to every
      Okazaki fragment during lagging strand DNA synthesis. Interestingly, whereas
      mammalian DNA ligase I functioned in the reconstituted replication system,
      mammalian DNA ligase III did not substitute and the phage T4 DNA ligase
      functioned inefficiently, suggesting that DNA ligase I has a specific role as a
      replicative DNA ligase in eukaryotic cells.

PMID- 8144678
TI  - Angiotensin II stimulates tyrosine phosphorylation of phospholipase C-gamma 1 in
      vascular smooth muscle cells.
AB  - The receptor for angiotensin II (Ang II) has recently been cloned; it is a
      receptor with seven transmembrane spanning domains that stimulates
      phosphoinositide hydrolysis upon ligand binding. The physiologic effects of Ang
      II are important in the regulation of vascular function. In this study, we
      examined the ability of Ang II to regulate the enzymatic activity of
      phospholipase C (PLC) in rat aortic vascular smooth muscle cells (VSMC). In
      cultured VSMC, PLC-gamma 1 and PLC-delta 1 isozymes, but not PLC-beta 1, were
      identified by Western analysis. Ang II (10(-7) M)-stimulated PLC-gamma 1
      phosphotyrosine phosphorylation with a maximum increase of 4.5-fold at 0.5 min.
      This followed the same time course as the Ang II-stimulated increase in inositol
      1,4,5-trisphosphate (1,4,5-IP3) levels. 1,4,5-IP3 formation was inhibited 75% by
      the tyrosine kinase inhibitor genistein (120 microM). Several growth factor
      receptors, such as the platelet-derived growth factor (PDGF) receptor are
      themselves tyrosine kinases and have been shown to phosphorylate PLC-gamma 1 and
      increase intracellular Ca2+ concentrations. The time course for PLC-gamma 1
      phosphorylation, IP3 formation, and Ca2+ mobilization by PDGF differed from Ang
      II in VSMC. The kinetics of the PDGF effects were slower in onset and more
      prolonged than those of Ang II. In summary, these findings show that Ang II
      stimulates VSMC phosphoinositide hydrolysis in association with tyrosine
      phosphorylation of PLC-gamma 1 and support the concept that Ang II-stimulated
      tyrosine phosphorylation is responsible for early signal transduction events.

PMID- 8144679
TI  - Interaction of the NH2- and COOH-terminal domains of the FLP recombinase with the
      FLP recognition target sequence.
AB  - The FLP protein that is encoded by the 2-microns plasmid of yeast Saccharomyces
      cerevisiae is a 45-kDa site-specific recombinase that belongs to the Int family
      of recombination proteins. FLP catalyzes a recombination event within the plasmid
      by binding specifically to each of three 13-base pair (bp) symmetry elements of
      the FLP recognition target (FRT). We have shown previously that partial
      proteolysis of the FLP protein by proteinase K resulted in a COOH-terminal
      fragment of size 32 kDa (P32) and an NH2-terminal fragment of 13 kDa (P13). In
      this study we have used footprinting with dimethyl sulfate to show that P32 binds
      specifically to the outer 9 bp of the 13 bp symmetry element. Binding of P13
      alone to the FRT site was not detectable in this assay. However, when P13 and P32
      were incubated together with the FRT site, protection of the remaining 4-bp
      region of the symmetry element was observed. To confirm these results we used
      bromodeoxyuridine (BrdU)-dependent UV cross-linking. P32 became cross-linked to
      the substrate that contained BrdU substitutions in the outer 9 bp of a 13-bp
      symmetry element, but not to one with the BrdU substitutions in the inner 4 bp.
      Reciprocally P13 cross-linked to the latter substrate but not the former. Cross
      linking was both BrdU and ultraviolet light-dependent. This study indicates that
      the COOH-terminal domain (P32) of FLP recognizes the outer 9 bp of the 13-bp
      symmetry element, whereas its NH2-terminal domain (P13) is needed for protection
      of the inner 4 bp of each symmetry element.

PMID- 8144680
TI  - Alternative splicing governs sulfation of tyrosine or oligosaccharide on
      peptidylglycine alpha-amidating monooxygenase.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal
      alpha-amidation of neuro-endocrine peptides through the sequential action of
      monooxygenase and lyase domains contained within this bifunctional protein.
      Alternative splicing leads to the expression of soluble and integral membrane
      bifunctional PAM proteins as well as a soluble monofunctional monooxygenase. In
      order to determine how alternative splicing affects post-translational
      modification of PAM proteins, we investigated the sulfation of PAM proteins
      expressed in stably transfected hEK-293 cells. Metabolic labeling with [35S]SO4(2
      ) or [35S]methionine and immunoprecipitation demonstrated that [35S]SO4(2-) was
      efficiently incorporated into PAM proteins that have the noncatalytic exon A
      region following the monooxygenase domain (PAM-1 and PAM-4) and into a soluble
      bifunctional PAM protein (PAM-3). Alkaline hydrolysis, radiosequencing, and
      deglycosylation experiments demonstrated the presence of a sulfated tyrosine
      (Tyr965) in the COOH-terminal domain of PAM-3 and multiple sulfated O-glycans in
      the exon A region of PAM-1 and PAM-4. A mutant PAM-3 protein in which Tyr965 was
      changed to Ala965 (PAM-3/Y965A) was not sulfated and exhibited monooxygenase and
      lyase activities similar to those of wild type PAM-3. Pulse-chase and temperature
      block experiments showed that the PAM-3/Y965A protein exits the trans-Golgi
      network faster than wild type PAM-3. Thus inclusion of exon A results in the
      sulfation of O-glycans, while elimination of the transmembrane domain results in
      the sulfation of Tyr965.

PMID- 8144681
TI  - Oncogenic activation of p59fyn tyrosine protein kinase by mutation of its
      carboxyl-terminal site of tyrosine phosphorylation, tyrosine 528.
AB  - As a result of alternative splicing, the Src-related tyrosine protein kinase
      p59fyn consists of two distinct isoforms termed FynB and FynT. Whereas the first
      product accumulates principally in brain, the second is expressed in hemopoietic
      cells, especially in T-lymphocytes. There is increasing evidence that the Fyn
      proteins are critical for normal functions of neuronal and lymphoid cells. To
      better understand the regulation of the catalytic function of p59fyn, we have
      tested the effects of mutating the major site of in vivo tyrosine
      phosphorylation, tyrosine 528, on the biological and biochemical properties of
      this enzyme. Our studies showed that a tyrosine 528-->phenylalanine (Y528F)
      mutation converted either Fyn isoform into a dominant oncoprotein, capable of
      full transformation of rodent fibroblasts. However, while both Y528F p59fynT and
      Y528F p59fynB were able to transform NIH 3T3 cells, activated FynT molecules were
      consistently more efficient at this process. It was also found that expression of
      wild-type p59fyn or kinase-defective Y528F Fyn molecules failed to provoke
      transformation of NIH 3T3 cells, implying that the transforming capabilities of
      Y528F Fyn relied on deregulated catalytic activity. Contrary to an earlier study
      (Cheng, S. H., Espino, P. C., Marshall, J., Harvey, R., Merrill, J., and Smith,
      A. E. (1991) J. Virol. 65, 170-179), these findings showed that mutation of the
      conserved carboxyl-terminal tyrosine residue markedly stimulated the catalytic
      function of p59fyn in vivo, implying that dephosphorylation of tyrosine 528 is
      sufficient to produce biologically relevant activation of the Fyn kinase.
      Moreover, our results provided further indication that the two Fyn isoforms
      possess distinct biochemical activities that may dictate functional differences
      in normal cell physiology.

PMID- 8144682
TI  - The active site substrate specificity of protein kinase C.
AB  - The active site substrate specificity of protein kinase C (PKC) has been
      evaluated. Like the cAMP-dependent protein kinase (PKA), PKC will efficiently
      phosphorylate achiral residues attached to an active site-directed peptide. In
      contrast, PKC exhibits behavior that is dramatically different from PKA with
      respect to the phosphorylation of alpha-substituted alcohols. Although PKA will
      only phosphorylate residues that contain the same stereochemistry as that found
      in L-serine, PKC will phosphorylate alpha-configurational isomers that correspond
      to both the L- and D-stereoisomers. The possible structural basis for the "dual
      specificity" of PKC is explored. In an analogous vein, although beta-substituted
      alcohols that serve as PKA substrates must contain the same stereochemistry as
      that present in L-threonine, PKC will phosphorylate configurational isomers which
      correspond to both L-threonine and L-allo-threonine. The implications of these
      observations with respect to protein kinase inhibitor design are discussed.

PMID- 8144683
TI  - Molecular sorting in polarized and non-polarized cells: common problems, common
      solutions.
AB  - We have been interested in determining how epithelial cells generate and maintain
      their characteristically polarized distributions of membrane proteins. Our
      efforts to date strongly indicate that the polarized transport in MDCK cells may
      be due to a set of discrete targeting determinants often found on a membrane
      protein's cytoplasmic domain. Surprisingly, these determinants are widely
      distributed and are not specific to proteins expressed in polarized cells. They
      also appear to function in controlling polarized transport along both the
      biosynthetic and the endocytic (or transcytotic) pathways. Signals for
      basolateral transport have been characterized and, like the cytoplasmic domain
      signal used by plasma membrane receptors for accumulation at clathrin-coated
      pits, they often involve a critical tyrosine residue. Although the basolateral
      and coated pit signals may also be co-linear, they are not identical. The
      basolateral and apical transport determinants are also hierarchically arranged.
      Although a single protein may contain one or more signals specifying basolateral
      transport, inactivation of these signals appears to reveal a determinant that
      directs efficient apical transport. Given that the sequence determinants
      responsible for polarized transport are not restricted to epithelial cells and
      are related to determinants commonly utilized in all cells, it is possible that
      non-polarized cells contain cognate apical and basolateral pathways that are
      responsible for 'constitutive' transport from the Golgi to the plasma membrane.
      The presence of two cognate pathways might confer a high degree of plasticity to
      pre-differentiated cells, allowing them rapidly to begin assuming a polarized
      phenotype in response to extracellular stimuli without requiring the synthesis of
      epithelial cell-specific transport machinery.

PMID- 8144684
TI  - Involvement of neurofilaments in motor neuron disease.
AB  - Motor neuron disease is clinically characterized by progressive muscle wasting
      leading to total muscle paralysis. A long history of pathological study of
      patients has firmly established that the primary lesion site is in spinal and
      cortical motor neurons. In addition to the wide-spread loss of these neurons,
      neuronal abnormalities including massive accumulation of neurofilaments in cell
      bodies and proximal axons have been also widely observed, particularly in the
      early stages of the disease. To test whether high accumulation of neurofilaments
      directly contributes to the pathogenic process, transgenic mice that produce high
      levels of neurofilaments in motor neurons have been generated. These transgenic
      mice show most of the hallmarks observed in motor neuron disease, including
      swollen perikarya with eccentrically localized nuclei, proximal axonal swellings,
      axonal degeneration and severe skeletal muscle atrophy. These data indicate that
      extensive accumulation of neurofilaments in motor neurons can trigger a
      neurodegenerative process and may be a key intermediate in the pathway of
      pathogenesis leading to neuronal loss.

PMID- 8144685
TI  - Ankyrin-binding activity of nervous system cell adhesion molecules expressed in
      adult brain.
AB  - A family of ankyrin-binding glycoproteins have been identified in adult rat brain
      that include alternatively spliced products of the same pre-mRNA. A composite
      sequence of ankyrin-binding glycoprotein (ABGP) shares 72% amino acid sequence
      identity with chicken neurofascin, a membrane-spanning neural cell adhesion
      molecule in the Ig super-family expressed in embryonic brain. ABGP polypeptides
      and ankyrin associate as pure proteins in a 1:1 molar stoichiometry at a site
      located in the predicted cytoplasmic domain. ABGP polypeptides are expressed late
      in postnatal development to approximately the same levels as ankyrin, and
      comprise a significant fraction of brain membrane proteins. Immunofluorescence
      studies have shown that ABGP polypeptides are co-localized with ankyrinB. Major
      differences in developmental expression have been reported for neurofascin in
      embryos compared with the late postnatal expression of ABGP, suggesting that ABGP
      and neurofascin represent products of gene duplication events that have
      subsequently evolved in parallel with distinct roles. Predicted cytoplasmic
      domains of rat ABGP and chicken neurofascin are nearly identical to each other
      and closely related to a group of nervous system cell adhesion molecules with
      variable extracellular domains, including L1, Nr-CAM and Ng-CAM of vertebrates,
      and neuroglian of Drosophila. A hypothesis to be evaluated is that ankyrin
      binding activity is shared by all of these proteins.

PMID- 8144686
TI  - Biogenesis of structural intercellular junctions during cleavage in the mouse
      embryo.
AB  - The preimplantation embryo differentiates the trophectoderm epithelium which,
      from the 32-cell stage, generates the blastocoel of the blastocyst and, after
      implantation, gives rise to most extraembryonic lineages of the conceptus.
      Trophectoderm differentiation begins at compaction (8-cell stage) when cell-cell
      adhesion, mediated by uvomorulin, and epithelial cell polarisation first occur.
      Here, we review our work on the biogenesis of tight junctions and desmosomes
      during epithelial differentiation. Tight junction construction begins at
      compaction and appears to be a gradual process, both at morphological and
      molecular levels. This maturation pattern may be due in part to sequential
      expression of tight junction constituents from the embryonic genome. Tight
      junction formation is dependent upon uvomorulin adhesion but can be inhibited by
      different means without apparently disturbing cell adhesion or polarisation. Cell
      interactions appear to regulate tight junction tissue specificity, in part by
      controlling the level of synthesis of constituents. Desmosome formation begins at
      the 32-cell stage, particularly as the embryo initiates blastocoel accumulation,
      and, in contrast with tight junction formation, does not appear to be a gradual
      process. Thus, nascent desmosomes appear mature in terms of their molecular
      composition. Desmosomal proteins are synthesised well in advance of desmosome
      formation but the synthesis of the principal glycoprotein components begins at
      the blastocyst stage and may regulate the timing of junction assembly.
      Implications of these differing patterns of biogenesis for the embryo are
      discussed.

PMID- 8144687
TI  - The making of a tight junction.
AB  - MDCK (epithelial cells from the dog kidney) plated at confluence, establish tight
      junctions in 12-15 hours through a process that requires protein synthesis,
      formation of a ring of actin filaments in close contact with the lateral membrane
      of the cells, calmodulin, and a Ca(2+)-dependent exocytic fusion of tight
      junction (TJ)-associated components. Monolayers incubated in the absence Ca2+
      make no TJs. Yet, if Ca2+ is added under these circumstances, TJs are made with a
      faster kinetics. Ca2+ is needed mainly at a site located on the outer side of the
      cell membrane, where it activates uvomorulin and triggers the participation of
      the cellular components mentioned above, via G-proteins associated with
      phospholipase C and protein kinase C. In principle, the sites of all these
      molecules and mechanisms involved in junction formation may be where a variety of
      agents (hormones, drugs, metabolites) act to produce epithelia with a
      transepithelial electrical resistance (TER) ranging from 10 to 10,000 omega.cm2.
      This range may be also due to a variety of substances found in serum and in
      urine, that increase the TER in a reversible and dose-dependent manner.

PMID- 8144688
TI  - Sorting of ion transport proteins in polarized cells.
AB  - The plasma membranes of polarized epithelial cells and neurons express distinct
      populations of ion transport proteins in their differentiated plasma membrane
      domains. In order to understand the mechanisms responsible for this polarity it
      will be necessary to elucidate the nature both of sorting signals and of the
      cellular machinery which recognizes and acts upon them. In our efforts to study
      sorting signals we have taken advantage of two closely related families of ion
      transport proteins whose members are concentrated in different epithelial
      plasmalemmal domains. The H+,K(+)-ATPase and the Na+,K(+)-ATPase are closely
      related members of the E1-E2 family of ion transporting ATPases. Despite their
      high degree of structural and functional homology, they are concentrated on
      different surfaces of polarized epithelial cells and pursue distinct routes to
      the cell surface in cells which manifest a regulated delivery pathway. We have
      transfected cDNAs encoding these pumps' subunit polypeptides, as well as chimeras
      derived from them, in a variety of epithelial and non-epithelial cell types. Our
      observations suggest that these pumps encode multiple sorting signals whose
      relative importance and functions may depend upon the cell type in which they are
      expressed. Recent evidence suggests that the sorting mechanisms employed by
      epithelial cells may be similar to those which operate in neurons. We have
      examined this proposition by studying the distributions of ion pumps and
      neurotransmitter re-uptake co-transporters expressed endogenously and by
      transfection in neurons and epithelial cells, respectively. We find that one of
      the classes of proteins we studied obeys the correlation between neuronal and
      epithelial sorting while another does not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144689
TI  - Gap junctions and tissue business: problems and strategies for developing
      specific functional reagents.
AB  - The complex and overlapping tissue distribution of different members of the gap
      junctional connexin protein family is reviewed. Intermixing of different
      connexins in the building of intercellular channels and translational and
      posttranslational regulation of gap junctional channels add additional challenges
      to the interpretation of the possible functions played by gap junction-mediated
      intercellular communication in tissue business.

PMID- 8144690
TI  - Epithelial cell adhesion and development of cell surface polarity: possible
      mechanisms for modulation of cadherin function, organization and distribution.
AB  - Epithelial cell adhesion is principally regulated by calcium-dependent cell
      adhesion proteins, termed cadherins. Recent studies indicate that cadherin
      function is modulated by a class of proteins, termed catenins, that bind to the
      cytoplasmic domain of cadherin. Here we review the evidence that catenins
      regulate cadherin function in cell-cell adhesion, and discuss their role in
      initiating cell surface polarity in epithelial cells.

PMID- 8144691
TI  - Characterization of recombinant E-cadherin (uvomorulin) expressed in insect
      cells.
AB  - Cadherins are Ca(2+)-dependent cell adhesion molecules that mediate cell adhesion
      by homophilic binding. Structural and functional analysis of the extracellular
      part of cadherins that mediates this binding has often been hampered by the
      availability of sufficient amount of protein. Therefore, we have expressed the
      extracellular region of E-cadherin (uvomorulin) using the baculovirus expression
      vector system (BEVS). A recombinant baculovirus was generated that encodes the
      signal peptide, the precursor region and the extracellular part of the mature
      protein, under the control of the promotor for polyhedrin. Infection of insect
      cells with recombinant virus led to the expression of about 40 mg of the E
      cadherin fragment per 2 x 10(9) infected cells. About half of the protein
      synthesized was secreted, either as mature protein or in its unprocessed form.
      The precursor peptide was removed by trypsin treatment in the presence of Ca2+
      and recombinant protein was purified to homogeneity. Biochemical characterization
      of the recombinant protein revealed a high degree of similarity with the mouse
      wild-type protein. Recombinant protein exhibited the known resistance to trypsin
      in the presence of Ca2+ and was recognized by two different conformation
      sensitive monoclonal anti-E-cadherin antibodies. Rabbit antibodies made against
      the recombinant protein recognized E-cadherin from different species. In spite of
      the high degree of structural resemblance recombinant E-cadherin was not able to
      inhibit E-cadherin mediated cell-cell adhesion.

PMID- 8144692
TI  - Catenins as mediators of the cytoplasmic functions of cadherins.
AB  - The catenins are polypeptides that bind to the conserved cytoplasmic tail of
      cadherins and are required for cadherin function. alpha-Catenin is related to
      vinculin and seems to be required for the interaction of cadherins with the actin
      cytoskeleton. beta-Catenin is homologous to armadillo, a segment polarity gene in
      Drosophila that participates in developmental signaling. Recent findings indicate
      that beta-catenin also participates in developmental signaling and embryonic
      patterning in Xenopus laevis. At least a portion of the electrophoretic band
      migrating at the position of gamma-catenin consists of plakoglobin, a desmosomal
      and zonula adherens protein that has high sequence similarity to beta-catenin and
      armadillo. The catenins may be involved in the regulation of cadherin function
      during tissue morphogenesis and tumorigenesis.

PMID- 8144693
TI  - Molecular mechanisms leading to loss of differentiation and gain of invasiveness
      in epithelial cells.
AB  - It has been realized for some time that the loss of epithelial differentiation in
      carcinomas, which is accompanied by higher mobility and invasiveness of the tumor
      cells, is a consequence of reduced intercellular adhesion. A variety of recent
      reports have indicated that the primary cause for the 'scattering' of the cells
      in invasive carcinomas is a loss of the integrity of intercellular junctions.
      Thus, defects in expression or structure of several components of the epithelial
      adherens junctions (e.g. E-cadherin, alpha-catenin) can occur, and our increased
      knowledge about the molecules of the junctions allows an explanation of these
      defects in molecular terms in some of the cases. Furthermore, tyrosine
      phosphorylation of junctional components (e.g. beta-catenin) appears to play a
      role in the assembly and disassembly of cell-cell contacts. Some of the effectors
      of epithelial junction formation are tyrosine protein kinases, e.g. the scatter
      factor/hepatocyte growth factor receptor c-Met, the FGF receptors and the pp60src
      kinase. The importance of tyrosine phosphorylation in junctions during tumor
      development is becoming increasingly evident.

PMID- 8144694
TI  - Patches and fences: probing for plasma membrane domains.
AB  - Cell plasma membranes appear to be composed of domains, patches whose composition
      and function differ from the average for an entire membrane surface. Proteins and
      lipids may be segregated into domains by different mechanisms. Some of these
      mechanisms are discussed, followed by a summary of the evidence for membrane
      domains obtained in my laboratory. This evidence is largely based on measurements
      of the lateral diffusion of membrane proteins and lipids. Recent new approaches
      to the interpretation of lateral diffusion measurements, consideration of so
      called fractal or long time-tails promise to give new insights into the stability
      and lifetime of membrane domains.

PMID- 8144695
TI  - Apical junctions and cell signalling in epithelia.
AB  - Genetic analysis in Drosophila has led to the identification of several proteins
      that mediate cell-cell interactions controlling the fate and proliferation of
      epithelial cells. These proteins are localized or enriched in the adherens and
      septate junctions at the apical end of the lateral membranes between cells. The
      proteins localized or enriched at adherens junctions include Notch, which is
      important for the cell interactions controlling neuroblast and bristle
      patterning; Boss and sevenless, which are required for the cell interaction that
      establishes the R7 photoreceptor cell; and Armadillo, required for the wingless
      dependent cell interactions that control segment polarity and imaginal disc
      patterning. Proteins localized at septate junctions include the product of the
      tumor suppressor gene dlg, which is required for septate junction formation,
      apical basal cell polarity, and the cell interactions that control proliferation.
      The results suggest that the cell signalling events important for cell fate
      determination and for cell proliferation control in epithelia occur at the apical
      junctions. The migration of the nucleus to the apical surface of the epithelium
      for mitosis may enable it to interact directly with the junction-associated
      signalling mechanisms.

PMID- 8144696
TI  - Responses to Wnt signals in vertebrate embryos may involve changes in cell
      adhesion and cell movement.
AB  - Wnt genes encode secreted glycoproteins, and, because of their homology with the
      Drosophila segment polarity gene wingless, are likely to play important roles as
      modulators of local intercellular signalling during embryonic development.
      Although little is known of the mechanisms by which Wnts signal in an autocrine
      or paracrine manner, it is increasingly clear that cells can respond rapidly to
      Wnt signals in the absence of transcription, and that these responses may include
      changes in cell adhesion and cell movement. We review recent evidence from
      studies on Xenopus laevis and other systems, which demonstrate that (1) a subset
      of Wnts modulate gap junctional permeability, which may be a reflection of
      changes in cadherin-mediated cell adhesion, (2) embryos express beta-catenin and
      plakoglobin, which are homologs of the armadillo gene products, known to be
      involved in the wingless signalling pathway, and known to be found at cell
      junctions, and (3) overexpression of specific Wnts in Xenopus embryos leads to
      clear changes in cell behavior and movement.

PMID- 8144697
TI  - The retinal pigment epithelium: a versatile partner in vision.
AB  - The retinal pigment epithelium (RPE) is a monolayer of cuboidal cells that lies
      in close association with the rod and cone photoreceptors. This epithelium has
      diverse features, three of which are discussed in some detail in this review,
      namely the daily phagocytosis of rod and cone outer segment fragments that are
      shed from their distal ends; the uptake, processing, transport and release of
      vitamin A (retinol) and some of its visual cycle intermediates (retinoids); and
      some of the aspects of its apical and basolateral membrane polarity that are the
      reverse of most other epithelia. Phagocytosis takes place at the apical surface
      via membrane receptor-mediated processes that are not yet well defined. Retinol
      uptake occurs at both the basolateral and apical surfaces by what appear to be
      separate receptor-mediated processes. The release of a crucial retinoid, 11-cis
      retinaldehyde (11-cis retinal), occurs solely across the apical membrane.
      Delivery of retinol across the basolateral membrane is mediated by a retinol
      binding protein (RBP) that is secreted by the liver as a complex with retinol
      (vitamin A). Within the cell, retinol and its derivatives are solubilized by
      intracellular retinoid binding proteins that are selective for retinol (cellular
      retinol binding protein, CRBP) and 11-cis retinoids (cellular retinal binding
      protein, CRALBP). Release of 11-cis retinal across the apical membrane and re
      uptake of retinol from the photoreceptors during the visual cycle is promoted by
      an intercellular retinoid binding protein (IRBP). Na,K-ATPase, the membrane
      integrated enzyme required to set up the ion gradients that drive other ion
      transporters, is largely localized to the apical membrane.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8144698
TI  - The role of transepithelial transport by M cells in microbial invasion and host
      defense.
AB  - Transepithelial transport of antigens by M cells in the epithelium associated
      with lymphoid follicles in the intestine delivers immunogens directly to
      organized mucosal lymphoid tissues, the inductive sites for mucosal immune
      responses. We have exploited M cell transport to generate and characterize
      specific monoclonal IgA antibodies that can prevent interaction of pathogens with
      epithelial surfaces. The relative protective capacities of specific monoclonal
      IgA antibodies have been tested in vivo by generation of hybridoma tumors that
      result in secretion of monoclonal IgA into the intestine. Using this method, we
      have established that secretion of IgA antibodies recognizing a single surface
      epitope on enteric pathogens can provide protection against colonization or
      invasion of the intestinal mucosa.

PMID- 8144699
TI  - Protein traffic in polarized epithelial cells: the polymeric immunoglobulin
      receptor as a model system.
AB  - As a model system to study protein traffic in polarized epithelial cells, we have
      used the polymeric immunoglobulin receptor. This receptor travels first to the
      basolateral surface, where it can bind polymeric IgA or IgM. The receptor is then
      endocytosed and delivered to endosomes. The receptor is sorted into transcytotic
      vesicles, which are exocytosed at the apical surface. The 103-amino acid
      cytoplasmic domain of the receptor contains several sorting signals. The 17
      residues closest to the membrane are an autonomous signal that is necessary and
      sufficient for basolateral sorting. For rapid endocytosis there are two
      independent signals, both of which contain critical tyrosine residues. Finally,
      transcytosis is signaled by phosphorylation of a particular serine.

PMID- 8144700
TI  - Epithelial polarity and differentiation in polycystic kidney disease.
AB  - Renal cysts are central pathological features in a number of human congenital and
      acquired diseases, and produce significant morbidity and mortality. This review
      describes our laboratory's efforts to identify specific alterations in epithelial
      cell polarity and differentiation associated with renal tubular cyst formation
      and progressive enlargement. Studies in a murine model of human autosomal
      recessive polycystic kidney disease, the C57BL/6J cpk/cpk (CPK) mouse have
      demonstrated quantitative (increased activity) and qualitative (apical membrane
      distribution) alterations in Na+,K(+)-adenosine triphosphatase activity that
      mediate tubular cyst formation. Proximal tubular cyst formation in CPK kidneys is
      characterized by increased activity of a basolateral Na+,K(+)-ATPase, which
      drives organic anion secretion and consequent tubular fluid secretion. In
      contrast, collecting tubule cyst formation is characterized by increased apical
      membrane Na+,K(+)-ATPase expression, which may be a marker of the relatively
      undifferentiated phenotype of cyst lining cells. If such apically expressed
      enzyme is active, it may have pathogenic import in collecting tubule cyst
      formation and enlargement by mediating net basal to apical vectorial solute and
      fluid transport.

PMID- 8144702
TI  - Role of heterotrimeric G proteins in polarized membrane transport.
AB  - MDCK cells maintain the polarized distribution of surface proteins mainly by
      sorting the newly synthesized proteins in the trans-Golgi network (TGN). In order
      to identify the components of the putative sorting machinery and to study factors
      that affect the sorting process, we have developed an in vitro system that
      reconstitutes the transport of viral glycoproteins from the TGN to the apical or
      basolateral surface. We have used this system to study effects of membrane
      impermeable reagents (such as peptides and antibodies) on the polarized
      transport. We observed that reagents affecting the stimulatory class (Gs) of
      heterotrimeric GTP binding proteins (G proteins) influenced the apical but not
      the basolateral transport. In contrast, reagents specific for the inhibitory
      class of G proteins (Gi) affected the basolateral but not the apical transport.
      These results show that the heterotrimeric G proteins differentially regulate the
      two pathways of polarized transport. The G proteins may regulate the process of
      polarized sorting of proteins in a fashion analogous to their role in signal
      transduction by providing a communication link with the cytosolic side of the
      membrane.

PMID- 8144701
TI  - Analysis of the trk NGF receptor tyrosine kinase using recombinant fusion
      proteins.
AB  - Nerve growth factor (NGF) represents a family of structurally related trophic
      factors, including brain-derived neurotrophin factor (BDNF), neurotrophin-3 (NT
      3), NT-4, and NT-5. These neurotrophin factors interact with two classes of
      receptors, the trk receptor tyrosine kinase family, and the low affinity p75
      neurotrophin receptor. To study potential ligand-receptor interactions,
      recombinant trk fusion proteins have been constructed, and pan-trk polyclonal
      antisera directed against the cytoplasmic tyrosine kinase domain have been
      generated. The recombinant proteins were assessed for in vitro kinase activity
      and for the ability of K-252a to inhibit phosphorylation. Antibodies made against
      the fusion protein recognize all trk family members, and are effective in
      immunoprecipitation of affinity-crosslinked receptors. Comparative crosslinking
      indicates that NGF can recognize all trk receptor members, illustrating the large
      number of potential ligand-receptor interactions between neurotrophins and their
      receptors.

PMID- 8144703
TI  - Distribution and role of heterotrimeric G proteins in the secretory pathway of
      polarized epithelial cells.
AB  - The movement of newly synthesized proteins in the constitutive secretory pathway,
      from their site of synthesis in the endoplasmic reticulum to the cell surface or
      to intracellular destinations, requires an orderly sequence of transport steps
      between membrane-bound compartments. Until recently, the trafficking and
      secretion of proteins through this pathway was thought to occur as a relatively
      automatic, unregulated series of events. Recent studies show that protein
      trafficking in the constitutive secretory pathway requires GTP hydrolysis by
      families of GTP-binding proteins (G proteins), which at multiple steps
      potentially provide regulation and specificity for protein trafficking. Many
      monomeric G proteins are known to be localized and functional on membrane
      compartments in the constitutive secretory pathway. Now, members of the
      heterotrimeric G protein family have also been localized on intracellular
      membranes and compartments such as the Golgi complex. We have studied the
      localization and targeting of G alpha subunits to distinct membrane domains in
      polarized epithelial cells. The distribution of different G alpha subunits on
      very specific membrane domains in cultured epithelial cells and in epithelial
      cells of the kidney cortex, is highly suggestive of roles for these G proteins in
      intracellular trafficking pathways. One of these G protein subunits, G alpha i-3,
      was localized on Golgi membranes. Studies on LLC-PK1 cells overexpressing G alpha
      i-3 provided evidence for its functional role in regulating the transport of a
      constitutively secreted heparan sulfate proteoglycan through the Golgi complex.
      Inhibition or activation of heterotrimeric G proteins by pertussis toxin or by
      aluminium fluoride respectively, have provided further evidence for regulation of
      intracellular transport by pertussis toxin-sensitive G proteins.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8144704
TI  - An electron microscopic study of TGN38/41 dynamics.
AB  - We have used electron microscopy to further characterize details of the dynamics
      of TGN38/41, a protein found to cycle between the trans-Golgi network and the
      plasma membrane. Immunogold-labeling of NRK cells under steady-state conditions
      shows the majority of TGN38/41 is localized to the trans-most Golgi cisternae and
      the trans-Golgi network. Small amounts of this molecule can be detected in early
      endosomes. Capture of cycling TGN38/41 molecules at the cell surface altered the
      steady state distribution. This was accomplished by binding TGN38/41 luminal
      domain antibodies to solid supports (beads), which were introduced to the culture
      media of cells. As increasing numbers of antigen-antibody complexes formed, the
      beads were internalized by the 'zippering mechanism' of phagocytosis. This
      provides a system that can address many questions related to the function of
      TGN38/41 and the trans-Golgi network itself.

PMID- 8144705
TI  - Endosomal pathways for water channel and proton pump recycling in kidney
      epithelial cells.
AB  - The plasma membrane composition of virtually all eukaryotic cells is maintained
      and continually modified by the recycling of specific protein and lipid
      components. In the kidney collecting duct, urinary acidification and urinary
      concentration are physiologically regulated at the cellular level by the
      shuttling of proton pumps and water channels between intracellular vesicles and
      the plasma membrane of highly specialized cell types. In the intercalated cell,
      hydrogen ion secretion into the urine is modulated by the recycling of vesicles
      carrying a proton pumping ATPase to and from the plasma membrane. In the
      principal cell, the antidiuretic hormone, vasopressin, induces the insertion of
      vesicles that contain proteinaceous water channels into the apical cell membrane,
      thus increasing the permeability to water of the epithelial layer. In both cell
      types, 'coated' carrier vesicles are involved in this process, but whereas
      clathrin-coated vesicles are involved in the endocytotic phase of water channel
      recycling, the transporting vesicles in intercalated cells are coated with the
      cytoplasmic domains of the proton pumping ATPase. By a combination of
      morphological and functional techniques using FITC-dextran as an endosomal
      marker, we have shown that recycling endosomes from intercalated cells are
      acidifying vesicles but that they do not contain water channels. In contrast,
      principal cell vesicles that recycle water channels do not acidify their lumens
      in response to ATP. These non-acidic vesicles lack functionally important
      subunits of the vacuolar proton ATPase, including the 16 kDa proteolipid that
      forms the transmembrane proton pore. Because these endosomes are directly derived
      via clathrin-mediated endocytosis, our results indicate that endocytotic clathrin
      coated vesicles are non-acidic compartments in principal cells. In contrast,
      recycling vesicles in intercalated cells contain large numbers of proton pumps,
      arranged in hexagonally packed arrays on the vesicle membrane. These pumps are
      inserted into the apical plasma membrane of A-type (acid-secreting) intercalated
      cells, and the basolateral plasma membrane of B-type (bicarbonate-secreting)
      cells in the collecting duct. Both apical and basolateral targeting of H(+)
      ATPase-containing vesicles in these cells may be directed by microtubules,
      because polarized insertion of the pump into both membrane domains is disrupted
      by microtubule depolymerizing agents. However, the basolateral localization of
      other transporting proteins in intercalated cells, including the band 3-like
      anion exchanger and facilitated glucose transporters, is not affected by
      microtubule disruption.

PMID- 8144706
TI  - Synaptic vesicle proteins and regulated exocytosis.
AB  - The recent identification of novel proteins associated with the membranes of
      synaptic vesicles has ignited the field of molecular neurobiology to probe the
      function of these molecules. Evidence is mounting that the vesicle proteins vamp
      (synaptobrevin), rab3A, synaptophysin, synaptotagmin (p65) and SV2 play an
      important role in regulated exocytosis, by regulating neurotransmitter uptake,
      vesicle targeting and fusion with the presynaptic plasma membrane.

PMID- 8144707
TI  - Membrane traffic in polarized neurons in culture.
AB  - Fetal hippocampal neurons develop axons and dendrites in culture. To study how
      neurons form and maintain different plasma membrane domains, hippocampal neurons
      were infected with RNA viruses and the distribution of the viral glycoproteins
      was analyzed by light and electron microscopy. Infection of hippocampal cells
      with vesicular stomatitis virus (VSV) and fowl plague virus (FPV) resulted in the
      polarized distribution of the newly synthesized viral glycoproteins. The VSV
      glycoprotein appeared firstly in the Golgi apparatus and then in the dendrites.
      In contrast, the hemagglutinin of FPV, after accumulation in the Golgi apparatus,
      moved to the axons. These results suggest that the mechanism of sorting of viral
      glycoproteins might be similar in neurons and MDCK cells, a cell line of
      epithelial origin. In these cells the VSV glycoprotein and the hemagglutinin of
      FPV distribute to the basolateral and apical membranes, respectively. Transport
      of viral glycoproteins to both neuronal domains was microtubule dependent.
      Nocodazole treatment of infected neurons inhibited the delivery of axonal and
      dendritic viral glycoproteins equally. To investigate if the analogy between
      epithelial cells and neurons extended to include an endogenous plasma membrane
      protein, the distribution of Thy-1, a GPI-linked protein, was analyzed. By
      immunofluorescence and immunoelectron microscopy, Thy-1 was found exclusively
      along the axonal surface. In epithelial cells GPI-anchored proteins are located
      apically. The existence of a barrier on the neuronal plasma membrane that would
      prevent intermixing of axonal and dendritic proteins was analyzed by a
      liposomefusion assay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144708
TI  - Polarity signals in epithelial cells.
AB  - In simple epithelia, specialized vectorial functions such as transport and
      secretion are made possible by the segregation of proteins and lipids into
      opposite surface domains. This polarized distribution results from selective
      delivery to and retention at the appropriate domain. In the case of direct
      delivery, the sorting site for apical and basolateral proteins is the trans-Golgi
      network (TGN) where they are incorporated into distinct apical and basolateral
      vesicles that are targeted to the respective surfaces. The machinery that
      controls this simple process is in fact rather complicated. It involves many
      different steps from the recognition event (between 'sorting signal(s)' and
      'sorting receptor(s)' to the formation of the vesicles, their budding, and the
      docking to the specialized plasma membrane domain. Here we summarize the latest
      developments in the sorting of apical and basolateral proteins, focusing in
      particular on the signals that are involved in this process and the current
      hypotheses about the mechanisms responsible for it, in both epithelia and in non
      polarized cells.

PMID- 8144709
TI  - Traffic of synaptic vesicle proteins in polarized and nonpolarized cells.
AB  - Neurons have at least two pathways of regulated secretion, which involve two
      classes of secretory organelles: typical synaptic vesicles (SVs) and large dense
      core vesicles. Large dense-core vesicles store and secrete peptide
      neurotransmitters and amines, and may be seen as the neuronal counterpart of
      secretory granules of endocrine cells. SVs are highly specialized secretory
      organelles, which store and secrete non-peptide hormones and play a dominant role
      in the fast, point-to-point signalling typical of the nervous system.
      Microvesicles that share a variety of biochemical and functional similarities
      with SVs (synaptic-like microvesicles) have recently been described in endocrine
      cells. SVs and synaptic-like microvesicles are closely related to vesicular
      carriers of the receptor-mediated recycling pathway. They undergo repeated cycles
      of exo-endocytosis, which are thought to involve endosomal intermediates. In
      mature neurons, SVs are concentrated in axon endings. To gain insight into the
      mechanisms responsible for SV targeting, we have studied the traffic of SV
      proteins in both endocrine cells and developing hippocampal neurons in primary
      culture at different stages of differentiation. Additionally, the distribution of
      the SV protein synaptophysin, when expressed by transfection in fibroblastic
      cells or in polarized epithelial cells (MDCK cells), was investigated. SV
      proteins are already present in developing neurons at stages preceding the
      establishment of neuronal polarity. As axons and dendrites form, SV proteins are
      found in both types of processes, although they become progressively more
      concentrated in the axon. Throughout these developmental stages SVs undergo
      active exo-endocytotic recycling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144710
TI  - Structure-activity relationships for skin sensitization potential: development of
      structural alerts for use in knowledge-based toxicity prediction systems.
AB  - The development of qualitative structure-activity relationships for the
      prediction of skin sensitization potential, based on structural alerts
      (substructures associated with a toxicological mechanism), and suitable for
      incorporation as rules into a knowledge-based system is described. The structure
      dependence of the skin sensitization mechanism may be largely defined in terms of
      the presence or metabolic/nonmetabolic formation of protein reactive functional
      groups on the test compound and by the physicochemical requirements of
      significant skin penetration. The proposed structural alerts were tested on a
      data set of diverse chemicals. The results showed that the alerts have potential
      as preliminary indicators of skin sensitization potential for a wide range of low
      molecular weight chemicals.

PMID- 8144711
TI  - SPROUT: recent developments in the de novo design of molecules.
AB  - SPROUT is a computer program for constrained structure generation. It is designed
      to generate molecules for a range of applications in molecular recognition. The
      program uses a number of approximations that enable a wide variety of diverse
      structures to be generated. Practical use of the program is demonstrated in two
      examples. The first demonstrates the ability of the program to generate candidate
      inhibitors for a receptor site of known 3D structure, specifically the GDP
      binding site of p21. In the second example, structures are generated to fit a
      pharmacophore hypothesis that models morphine agonists.

PMID- 8144712
TI  - Oh, yeah.

PMID- 8144713
TI  - The forgotten vital signs.

PMID- 8144714
TI  - Exertional dyspnea and headache in a 16-year-old girl.

PMID- 8144715
TI  - Idiopathic edema.

PMID- 8144716
TI  - PID prevention: clinical and societal stakes.
AB  - Pelvic inflammatory disease continues to take its physical, psychological, and
      financial tolls. Prompt treatment of symptomatic disease and screening of
      asymptomatic or mildly symptomatic women for the major causative organism-
      Chlamydia trachomatis--are the keys to preventing serious sequelae, such as
      chronic pelvic pain, ectopic pregnancy, and infertility.

PMID- 8144717
TI  - Case in point. Postinfectious acute glomerulonephritis.

PMID- 8144718
TI  - Secondary hypertension: workup and correction.
AB  - The three most common causes--renal artery stenosis, pheochromocytoma, and
      primary aldosteronism--are reviewed, including uncomplicated screening procedures
      to select candidates for a more intensive workup. The first two conditions are
      usually corrected by angioplasty or surgery, whereas aldosteronism may require
      both surgical and medical therapy or medication alone.

PMID- 8144719
TI  - Wound botulism.

PMID- 8144720
TI  - Marijuana has no medicinal value.

PMID- 8144721
TI  - Another cause of gynecomastia.

PMID- 8144722
TI  - Look in their eyes.

PMID- 8144723
TI  - Case in point. Menetrier's disease.

PMID- 8144724
TI  - Fever, leukocytosis, and an enlarging flank mass.

PMID- 8144725
TI  - Differentiating the diabetic neuropathies.

PMID- 8144726
TI  - Prehospital thrombolysis in myocardial infarction.
AB  - Studies comparing paramedic-initiated and hospital-initiated therapy show that
      the critical issue is not where or by whom thrombolysis is started but when it is
      started. Two of the greatest time-savers--and hence modifiers of infarct size and
      mortality--have been the introduction of the computer-interpreted ECG and simply
      alerting the hospital that a patient with a diagnosed acute MI will be arriving
      shortly.

PMID- 8144727
TI  - An irregular rhythm after cardioversion.

PMID- 8144728
TI  - Biliary extracorporeal shock-wave lithotripsy: an update.
AB  - Since the mid-1980s, numerous clinical studies, involving hundreds of patients,
      have attested to the safety and efficacy of this technique. There have been no
      deaths, and occasional soft tissue damage appears to be temporary.

PMID- 8144729
TI  - Microbiological and clinical effects of metronidazole and amoxicillin in
      Actinobacillus actinomycetemcomitans-associated periodontitis. A 2-year
      evaluation.
AB  - In this study, we evaluated the microbiological and clinical effects of
      mechanical debridement in combination with metronidazole and amoxicillin therapy
      in 48 patients with Actinobacillus actinomycetemcomitans-associated
      periodontitis, 3 months and at least 24 months after active treatment. The
      results of this study showed that 47 out of 48 patients were still negative for
      A. actinomycetemcomitans subgingivally, at the mucous membranes, the tonsillar
      area and in the saliva, 2 years after therapy. The clinical results showed that a
      reduction of probing pocket depth, probing attachment level, bleeding index and
      plaque index was not only seen in the time between baseline and 3 months after
      therapy, but further clinical improvement was observed between 3 and 24 months
      after active treatment. We conclude that combined mechanical debridement and
      metronidazole plus amoxicillin therapy is very effective in suppressing A.
      actinomycetemcomitans below cultivable levels over a long period of time,
      suggesting elimination of this organism, and that recolonization of A.
      actinomycetemcomitans seems to be a rare event. The elimination of A.
      actinomycetemcomitans is paralleled by a further improvement of the periodontal
      status of the patients, even up to 24 months after active treatment.

PMID- 8144730
TI  - Experiences with guided tissue regeneration in the treatment of advanced
      periodontal disease. A clinical re-entry study. Part I. Vertical, horizontal and
      horizontal periodontal defects.
AB  - The aim of this study was to evaluate the predictability of guided tissue
      regeneration (GTR), using ePTFE-membranes (Gore-Tex) in the treatment of advanced
      periodontal disease. The study presents long-term results for 88 teeth in 23
      patients at least 9 months after membrane surgery. The periodontal lesions
      included severe horizontal and/or vertical bone loss. The bone level (BL and BL')
      and the tissue level (TL), a new parameter between cemento-enamel junction and
      coronal margin of the tissue in the defect, were recorded during surgery:
      immediately before application of the membrane (BL), after membrane removal (TL)
      and during a re-entry procedure (BL') 9 to 12 months later. The average tissue
      gain in the periodontal defect (BL-Tl) at membrane removal was 65.7% (p < 0.001)
      and the average gain in mineralized tissue at re-entry (BL-BL'), 30.4%, meaning
      more than 46% of the gained tissue at removal was mineralized at re-entry. The
      decreased amount of mineralized tissue at re-entry in relation to the tissue gain
      at membrane removal might be due to formation of a so-called long connective
      tissue attachment or to mineralization-induced shrinkage of the new tissue and
      some surgical difficulties in coverage of the newly formed tissue. Nevertheless,
      an absolute gain of 31% mineralized tissue after GTR can provide a marked
      improvement in the prognosis of a periodontally severely damaged tooth.

PMID- 8144731
TI  - The relationship of beta-glucuronidase activity in crevicular fluid to clinical
      parameters of periodontal disease. Findings from a multicenter study.
AB  - Previous reports have suggested that persistently elevated levels of the acidic
      glycohydrolase beta-glucuronidase (beta G) in gingival crevicular fluid (GCF) can
      identify patients with chronic adult periodontitis who are at risk for future
      probing attachment loss (PAL). To comprehensively study beta G activity in GCF, a
      multicenter trial examining the relationship of the enzyme in GCF to traditional
      clinical parameters of periodontal disease and PAL was conducted. In this report,
      the baseline data was used to evaluate the relationship of beta G activity in GCF
      to traditional parameters of periodontal disease. The study group included 130
      patients who had been treated for periodontal disease and were on a regular
      recall schedule, and 10 patients with chronic adult periodontitis who had never
      received treatment. Upon entering the longitudinal trial, the patients were
      examined, and a standardized 30-s GCF sample was collected from the mesiobuccal
      crevice of all study teeth. As a control, GCF samples and clinical data were
      collected from 62 patients with a healthy periodontium or mild inflammatory
      gingivitis without loss of probing attachment. At baseline, beta G activity for
      the periodontitis patients ranged from 0 to 1704 Units (U), with a median of 32
      U. beta G could not be detected in 0.2% of samples (activity < or = 2.0 U). The
      90% cumulative relative frequency was 139 U. For the healthy/gingivitis subjects
      beta G activity ranged from 0 to 504 U, with a median of 22 U. Enzyme was not
      detectable in 0.4% of samples. Only 0.9% of samples contained greater than 139 U.
      beta G activity in GCF was not related to gender or age. For the periodontitis
      patients, elevated enzyme activity (> or = 140 U) was most often associated with
      molar teeth, followed by maxillary bicuspids. Maxillary central incisors, and
      mandibular central and lateral incisors displayed the lowest frequency of
      elevated enzyme activity. The relationship of beta G activity to the traditional
      parameters of probing depth and bleeding on probing was assessed. For shallow
      sites (1.0-1.5 mm, 2.0-2.5 mm probing depth), the large majority of GCF samples
      contained low enzyme activity (90% of samples < 50 U). Descriptive indicators
      demonstrated a trend of increased beta G activity with increased probing depth.
      The median beta G activity shifted from 15 U for the shallowest sites (1.0-1.5
      mm) to 127 U for the deepest sites (5-8 mm). However, this was due to a
      broadening of the distribution rather than representing a shift in the
      distribution profile.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8144732
TI  - Studies on the relationship between changes in radiographic bone height and
      probing attachment.
AB  - The aim of this investigation was to determine the relationship between loss of
      radiographic crestal bone height and probing attachment loss. As part of this
      aim, we are introducing a new method for determination of a threshold for
      significant probing attachment loss which takes into account the error
      contributed by alteration in tissue tone. 57 adults with established
      periodontitis were selected. Radiographs were taken using the Rinn alignment
      system. Crestal change was determined from bone height measurements on digitized
      images of pairs of radiographs using the "side-by-side" technique of analysis
      developed recently by us. Probing attachment loss was measured using the Florida
      electronic probe system. Radiographic and probing measurements were made at
      baseline and after 1 year. No treatment was given during this period. A direct
      and significant relationship was observed between radiographic bone loss and
      probing attachment loss on a site basis (p = 0.0001, r2 = 0.018) and between
      subject means (p = 0.0014, r2 = 0.16). Radiographic and probing attachment change
      at all categories of sites, dichotomously classified as to not changing or
      loosing indicated 13% of sites were loosing by measurement of radiographic change
      and 9.6% were loosing by measurement of attachment change. Concordance in
      radiographic and attachment level change was found in 82% of sites examined. The
      relative diagnostic import of change in probing attachment or change in
      radiographic bone height requires treatment outcome studies based on use of
      diagnostic information of the 2 measuring techniques used singly and in
      combination.

PMID- 8144733
TI  - A cohort study of radiographic alveolar bone loss during adolescence.
AB  - The aim of the present study was to assess the changes in prevalence of early
      radiographic alveolar bone loss in a birth cohort (all subjects born 1970) over a
      period of 8 years as related to sex, ethnic origin, orthodontic treatment and
      socio-economic status. In 1984, the target population consisted of 2767 subjects.
      In 1986, 1988 and 1992, sets of bite-wing radiographs were obtained from samples
      of the same population. Alveolar bone loss was recorded if the distance from the
      cemento-enamel junction to the alveolar crest exceeded 2 mm measured on posterior
      bite-wing radiographs. The frequency of subjects with radiographic alveolar bone
      loss increased significantly with age (p < 0.05). The number of subjects with 3
      or more lesions also increased with age. The demographic variables studied did
      not seem to influence the prevalence of bone loss significantly in the present
      cohort study.

PMID- 8144734
TI  - The long-term effect of an oscillating/rotating electric toothbrush on
      gingivitis. An 8-month clinical study.
AB  - The purpose of this study was to evaluate the safety and efficacy of the Braun
      Plak Control for the removal of supragingival plaque and improving gingival
      health in a long-term clinical trial, and to compare it to regular manual
      toothbrush. Assessed were plaque accumulation, amount of gingival inflammation,
      gingival bleeding on probing, and calculus. In total, 77 young individuals were
      selected on the basis of having 'moderate gingivitis'. They were monitored over 8
      months and divided among 2 groups; a control group that used a manual toothbrush
      and a test group that used the Braun Plak Control. The clinical assessments were
      repeated after 1, 2, 5, and 8 months. At baseline, subjects were handed their
      assigned toothbrushes together with written oral hygiene instructions. They were
      instructed to brush for at least 2 min. 1 month after baseline examinations, all
      subjects received a professional prophylaxis and oral hygiene instruction from an
      experienced dental hygienist. Plaque removal was reinforced at the 2-and 5-month
      examination. In conclusion, results indicate that the Braun Plak Control is a
      safe and efficient home care device. At the end of this trial, this electric
      toothbrush proved to be more effective than a regular manual toothbrush.

PMID- 8144735
TI  - Topical metronidazole as an adjunct to subgingival debridement in the treatment
      of chronic periodontitis.
AB  - The purpose of this study was to evaluate the clinical effects of a single
      application of a 5% metronidazole collagen device in periodontal pockets deeper
      than 5 mm, in association with debridement and without reinforcement of home care
      and hygiene as practiced by the patient at any time. Pocket depth, attachment
      level, bleeding on probing, gingival index and plaque index were assessed at
      baseline, and on days 15, 30 and 90. Analysis of data from 28 patients indicated
      that both debridement and metronidazole therapy decreased pocket depth, bleeding
      on probing and gingival index, but results were significantly better with
      metronidazole. These results indicate that topical metronidazole provides an
      effective adjunctive treatment of advanced periodontitis.

PMID- 8144736
TI  - Subgingival distribution of A. actinomycetemcomitans in periodontitis.
AB  - This investigation developed an experimental design that (1) detailed the
      distribution of A. actinomycetemcomitans in subgingival plaque related to the
      level of serum antibody to this pathogen; (2) used broad based subgingival plaque
      sampling to allow a definition of the distribution of A. actinomycetemcomitans
      infection in periodontitis patients; (3) described the distribution of A.
      actinomycetemcomitans serotypes in patients and within sites; and, (4) assessed
      how this infection impacted upon local clinical symptoms of disease. We noted a
      significant positive relationship between the level of IgG anti-A.
      actinomycetemcomitans antibody and the frequency of teeth infected until nearly
      13 teeth demonstrated an infection. Furthermore, the results showed a generally
      negative relationship between the antibody level and the burden of A.
      actinomycetemcomitans in the infected sites. Interproximal sites associated with
      first molar teeth were the predominant sites for subgingival colonization;
      incisors were also frequently infected in this population. The first molar teeth
      also exhibited the greatest level of A. actinomycetemcomitans, while the incisors
      demonstrated a high level of A. actinomycetemcomitans in individual sites. The
      results clearly indicated the majority of the sites sampled were colonized by a
      single serotype of A. actinomycetemcomitans. We detected A. actinomycetemcomitans
      nearly 2 x times more frequently and a significant increase in the proportion of
      A. actinomycetemcomitans was found in samples obtained from teeth with bleeding
      on probing. The results also showed a significant trend for both pocket depth and
      attachment levels to be related to the presence and proportion of A.
      actinomycetemcomitans in the subgingival plaque. These findings detail the
      microbiological, immunological and clinical characteristics of a unique subset of
      periodontitis patients that appear to exhibit disease associated (caused?) with
      A. actinomycetemcomitans infection irrespective of clinical categorization. The
      results support a unique distribution of this microorganism in the subgingival
      ecology that is related to active host immune responses and clinical presentation
      of the tooth.

PMID- 8144737
TI  - Prevalence of periodontitis and suspected periodontal pathogens in families of
      adult periodontitis patients.
AB  - The aim of the present study was to investigate the prevalence of
      periodontopathic microorganisms and periodontal destruction in the spouses and
      children of adult periodontitis patients. For this study, 24 families were
      selected on the basis of one parent with severe periodontal breakdown and the
      presence of Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis
      and/or more than 30% Prevotella intermedia subgingivally. The clinical
      examination of both parents and children included pocket depth and clinical
      attachment loss (CAL) measurements. Samples for bacterial examination were
      obtained from the mucous membranes, the saliva and pockets. Pocket selection was
      based on the most advanced periodontitis situation found in a subject. The
      samples were cultured for the detection of A. actinomycetemcomitans, P.
      gingivalis and P. intermedia. By phase-contrast microscopy, the % of spirochetes
      and motile microorganisms was assessed. The number of children within each family
      varied between 1 and 3. In total 49 children were investigated with a range in
      age of 3 months to 15 years. Results showed that under the age of 5 years, none
      of the children had CAL, whereas in the age group of 5-15 years, 26.5% had 1-5
      sites in the primary and/or permanent dentition with 1-3 mm CAL. 3 of the spouses
      had no interproximal CAL. 16 of the 24 spouses had a light to moderate form of
      periodontitis, with at least one site with 1 to 4 mm CAL and 5 spouses had severe
      periodontal breakdown with sites showing at least 8 mm CAL. Spirochetes, motile
      microorganisms and P. intermedia were frequently present in all family members.
      18 out of the 24 probands were positive for P. gingivalis. This organism was
      found once only in a 5-year-old boy and in 11 of the spouses. A.
      actinomycetemcomitans was detected in 13 probands; 5 children and 5 of the
      spouses were also positive for this bacterium. If a child harboured one of the
      periodontopathogens, at least 1 of the parents was also positive for that
      bacterium. This phenomenon may be due to transmission of microorganisms between
      family members. Comparison of the clinical data reported in the present study
      with similar clinical parameters from epidemiological studies of the Dutch
      population suggest that the spouses and children of adult periodontitis patients
      might be at relatively high risk of developing periodontal breakdown.

PMID- 8144738
TI  - Comparison of a manual and a new electric toothbrush for controlling plaque and
      gingivitis.
AB  - In the present clinical trial, the effect on existing plaque and gingivitis of a
      new electric toothbrush (ET) was compared to that of a manual toothbrush (MT). 40
      medical students, age 18-30 years, participated. Plaque index (PlI) and gingival
      index (GI) were recorded at 6 sites at all teeth. At baseline, a PlI and GI > 1
      were required. The participants were at random allocated to a group using either
      ET or MT and were instructed only to use the assigned toothbrush, brushing each
      morning and evening for 2 min. No oral hygiene instruction was given. Re
      examination was done after 1, 2 and 6 weeks. In the MT group, a minor decrease in
      mean PlI was found after 6 weeks (all sites: from 1.2 to 1.1, approximal sites:
      from 1.4 to 1.2). The corresponding figures in the ET group were: 1.2 to 0.6 and
      1.4 to 0.8. After 6 weeks, the % of sites with visible plaque with MT was: 24%
      (all sites) and 30% (approximal sites) and with ET 8% and 9%, respectively. With
      MT, mean GI was unchanged after 6 weeks compared to baseline, whereas with ET,
      the changes were from 1.1 to 0.9 (all sites) and from 1.1 to 1.0 (approximal
      sites). The % of sites with GI score > or = 2 had not changed after 6 weeks with
      MT (all sites: 11%, approximal sites: 13%). With ET, these results were 3% and
      4%, respectively.

PMID- 8144739
TI  - The effect of smoking on the response to periodontal therapy.
AB  - This study evaluated the effect of smoking on the clinical response to non
      surgical and surgical periodontal therapy. 74 adult subjects with moderate to
      advanced periodontitis were treated according to a split-mouth design involving
      the following treatment modalities: coronal scaling, root planing, modified
      Widman surgery, and flap with osseous resectional surgery. Clinical parameters
      assessed included probing depth, probing attachment level, horizontal attachment
      level in furcation sites, recession, presence of supragingival plaque and
      bleeding on probing. Data were collected: initially, 4 weeks following phase-I
      therapy, 10 weeks following phase-II therapy and on a yearly basis during 6 years
      of maintenance care. Data analysis demonstrated that smokers exhibited
      significantly less reduction of probing depth and less gain of probing attachment
      level when compared to non-smokers immediately following active therapy and
      during each of the 6 years of maintenance (p < 0.05). A greater loss of
      horizontal attachment level was evident in smokers at each yearly exam during
      maintenance therapy (p < 0.05). There were no differences between groups in
      recession changes. In general, these findings were true for the outcomes
      following all 4 modalities of therapy and were most pronounced in the deepest
      probing depth category (> or = 7 mm). Statistical analysis showed a tendency for
      smokers to have slightly more supragingival plaque and bleeding on probing. In
      summary, smokers responded less favorably than non-smokers to periodontal therapy
      which included 3-month maintenance follow-up.

PMID- 8144740
TI  - Microbial identification and antibiotic sensitivity testing, an aid for patients
      refractory to periodontal therapy. A report of 3 cases.
AB  - The importance of microbial surveillance is illustrated in 3 clinical cases. Each
      case demonstrated a continued lack of response to conventional periodontal
      treatment. Repeated bouts of periodontal abscess formation and bone loss occurred
      over a 3- to 4-year period, despite numerous surgeries supplemented with
      antibiotics. As a result, patients were termed refractory to treatment and
      extensive microbiological analysis and sensitivity testing was performed.
      Following institution of the appropriate antibiotic and conservative therapy
      consisting of several sessions of scaling and root planning, each of these cases
      demonstrated a dramatic remission of disease progression. No further breakdown
      has been seen for a minimum of 2 1/2 years. While anecdotal in nature, these
      cases support the usefulness of microbial identification coupled with antibiotic
      sensitivity as an adjunct to conventional conservative periodontal therapy.

PMID- 8144741
TI  - Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among cell
      morphology, intrinsic electrophysiological properties, and axon targets.
AB  - Previous work has established two structure/function correlations for pyramidal
      neurons of layer 5 of the primary visual cortex of the rat. First, cells
      projecting to the superior colliculus have thick apical dendrites with a florid
      terminal arborization in layer 1, whereas those projecting to the visual cortex
      of the opposite hemisphere have thinner apical dendrites that terminate below
      layer 1, without a terminal tuft (e.g., Hallman et al.: J Comp Neurol 272:149,
      '90). Second, intracellular recording combined with dye injection has revealed
      two classes of cells: the first has a thick, tufted apical dendrite and fires a
      distinctive initial burst of two or more impulses, of virtually fixed, short
      interspike interval, in response to current injection; and the other, with a
      slender apical dendrite lacking a terminal tuft, tends to have a longer membrane
      time constant and higher input resistance, and does not fire characteristic
      bursts (e.g., Larkman and Mason: J Neurosci 10:1407, '90). The present study
      combined intracellular recording in isolated slices of rat visual cortex and
      injection of carboxyfluorescein, to reveal soma-dendritic morphology, with prior
      injection of rhodamine-conjugated microspheres into the superior colliculus or
      contralateral visual cortex to label neurons according to the target of their
      axons. This permitted a complete correlation of morphology, intrinsic
      electrophysiological properties, and identity of the projection target for
      individual pyramidal cells. Neurons retrogradely labeled from the opposite visual
      cortex were found in all layers except layer 1 while those labeled from the
      superior colliculus lay exclusively in layer 5. Within layer 5 interhemispheric
      cells were more concentrated in the lower half of the layer but extensively
      overlapped the distribution of corticotectal cells. Every cell studied that
      projected to the superior colliculus was of the bursting type and had a thick
      apical dendrite with a terminal tuft. Every cell in this study projecting to the
      opposite visual cortex was a "nonburster" and had a slender apical dendrite with
      fewer oblique branches that ended without a terminal tuft, usually in the upper
      part of layer 2/3. Interhemispheric cells also had rounder, less conical somata
      and generally had fewer basal dendrites than corticotectal neurons. Many cells
      with the physiological and morphological characteristics of interhemispheric
      cells were not back-labeled from the opposite visual cortex, implying that
      pyramidal cells of this type can have other projection targets (e.g., other
      cortical sites in the ipsilateral hemisphere).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8144742
TI  - Pyramidal neurons in layer 5 of the rat visual cortex. II. Development of
      electrophysiological properties.
AB  - Two major classes of pyramidal neurons can be distinguished in layer 5 of the
      adult rat visual cortex. Cells of the "thick/tufted" type have stout apical
      dendrites with terminal tufts, and most of them project to the superior
      colliculus (Larkman and Mason: J Neurosci 10:407, '90; Kasper et al.: J Comp
      Neurol, this issue, 339:459-474). "Slender/untufted" cells have thinner apical
      trunks with no obvious terminal tufts, and a substantial proportion of them
      project to the contralateral visual cortex. These two types also differ in their
      intrinsic electrophysiological features. In this study we describe the postnatal
      maturation of the electrophysiological and synaptic properties of layer 5
      pyramidal neurons and relate these findings to the morphological development and
      divergence of the two cell types. Living slices were prepared from the visual
      cortex of rats aged between postnatal day 3 (P3) and young adults and maintained
      in vitro. Stable intracellular impalements were obtained from a total of 63
      pyramidal cells of layer 5 at various ages, which were injected with biocytin so
      that morphological and electrophysiological data could be obtained from the same
      cell. Before P15, injection of a single cell sometimes stained a cluster of
      neurons of similar morphology, probably as a result of dye coupling. The
      incidence of such clustering and the number of neurons within each cluster
      decreased with age. There was no obvious difference in electrophysiological
      properties between cells in clusters and age-matched, noncoupled neurons. From
      P5, the apical dendrites of neurons could easily be classified as "thick/tufted"
      or "slender/untufted." On average, the resting potential became more negative,
      and membrane time constant and input resistance decreased with age.
      Electrophysiological differences between the "thick/tufted" and
      "slender/untufted" cell types did not become apparent until the third postnatal
      week, after which the "thick/tufted" cells on average had lower input resistances
      and slightly faster time constants than "slender/untufted" cells. The current
      voltage relations of the neurons became progressively more nonlinear during
      maturation, with both rapid inward rectification and time-dependent rectification
      or "sag" becoming more prominent. There were also changes in the amplitude and
      waveform of action potentials, which generally approached adult values by 3 weeks
      of age. Action potential threshold became more negative, both in absolute terms
      and relative to the resting membrane potential. Action potentials became larger
      in peak amplitude and of shorter duration, with both rise and fall times
      decreasing progressively during development.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8144743
TI  - Pyramidal neurons in layer 5 of the rat visual cortex. III. Differential
      maturation of axon targeting, dendritic morphology, and electrophysiological
      properties.
AB  - This paper describes the early morphological and physiological development of
      pyramidal neurons in layer 5 of the rat visual cortex in relation to the targets
      chosen by their axons. Cells were prelabeled by retrograde transport from the
      superior colliculus or the contralateral visual cortex and intracellularly
      injected either in fixed slices or after recording in living slices. In the
      adult, corticotectal cells have thick apical dendrites with an extensive terminal
      arborization extending into layer 1, and fire characteristic bursts of action
      potentials when injected with a depolarizing current; interhemispheric cells have
      slender apical dendrites that terminate without a terminal tuft, usually in layer
      2/3, and they display a more regular firing pattern (Kasper et al.: J Comp
      Neurol, this issue, 339:459-474). At embryonic day E18 (when axons of the two
      classes of cells are already taking different routes towards their targets) and
      E21, pyramidal-like cells throughout the cortical plate all have similar soma
      dendritic morphology, with spindle-shaped cell bodies and few, short basal
      dendrites but apical dendrites that all end in distinct tufts in the marginal
      zone. At postnatal day P3, after the axons of both cell classes have reached
      their targets, all pyramidal neurons in layer 5 still have distinct terminal
      arborizations in layer 1, though they vary in complexity and extent. The somata
      are now more mature (round to ovoid in shape), and the basal dendritic tree has
      extended. As early as P5, all cells studied could be clearly classified as tufted
      or untufted (considerably earlier than previously reported; Koester and O'Leary:
      J Neurosci 12:1382, '92), and these features correlated precisely with the
      projection target, as in the adult. Measurement showed that although
      interhemispheric cells lose their terminal tufts, in general the trunks of their
      apical dendrites do not withdraw but continue to grow, at roughly the same rate
      as those of corticotectal cells. The two classes of layer 5 pyramidal neurons
      differentiate from each other in three distinct phases: pathway selection by
      axons precedes the loss of the apical tuft by interhemispheric cells, and these
      morphological characteristics are established 10 days before the onset of burst
      firing in corticotectal cells. These three steps may be guided by different
      molecular signals.

PMID- 8144744
TI  - Distribution of cytochrome oxidase and parvalbumin in the primary visual cortex
      of the adult and neonate monkey, Callithrix jacchus.
AB  - The anatomical distributions of the mitochondrial enzyme cytochrome oxidase (CO)
      and of the calcium binding protein parvalbumin (PV) were studied in the striate
      cortex of adult and neonate New World monkeys (Callithrix jacchus). In the adult
      marmoset, both proteins were found in laminar arrangements similar to those
      described for the macaque monkey, with prominent bands of PV-like immunoreactive
      (PV-LI) puncta in layers IV and IIIb, and fairly evenly distributed PV-LI
      nonpyramidal neurons. Furthermore, the pattern of CO activity in area 17 of the
      neonate marmoset was almost identical to the CO pattern described in neonate
      macaque and squirrel monkeys. It came, therefore, as a surprise to find that the
      adult pattern of PV-like immunoreactivity (PV-LI) in the marmoset striate cortex
      arises from a neonatal pattern strikingly different from that seen in any
      developmental stage of the macaque, or in any other mammal studied so far. In the
      deep layers IV through VI of the neonate marmoset, a large number of PV-LI
      neurons was stained in bandlike patterns, their number in layers IV and V
      exceeding the number of PV-LI neurons present in these layers of the adult
      marmoset area 17. Staining of layers IV and VI was restricted to area 17 and
      involved nonpyramidal cells and their processes. The stained band of layer V, in
      contrast, continued throughout most of the neocortex. In area 17, an estimated 10
      to 20% of the stained cells in layer V exhibited pyramidal shapes. The findings
      show that the expression of PV by visual cortical cells occurs before birth and
      suggest that the comparatively early onset of PV expression is not dependent on
      the onset of textured vision. The exuberant number of stained cells in some
      layers, and particularly the staining of pyramidal cells, in the neonate
      marmoset, suggest that a considerable number of cells possesses the stainability
      for PV-LI only transiently, i.e., in the marmoset, these cells have a specific
      demand for parvalbumin during this phase of their development.

PMID- 8144746
TI  - Quantitative aspects of the GABA circuitry in the primary visual cortex of the
      adult rat.
AB  - The number and size of synaptic contacts made by GABA-immunoreactive axonal
      boutons were estimated in each layer of the primary visual cortex (area Oc1M) of
      adult rats by using the dissector method. Immunoreactivity for GABA was detected
      with the postembedding immunogold technique on ultrathin sections. Targets of
      GABA synaptic contacts were also identified to predict the sites of GABA
      influence in the rat visual cortex. For the total cortical depth, 82 million out
      of an overall population of 666 million synaptic contacts per mm3 of tissue (or 1
      in 8 contacts, 12%) were GABA. Layer IV averaged 62% more GABA contacts per unit
      volume than did any other cortical layer. Consequently, these represented a
      larger proportion (1 in 6, 17%) of the overall population of layer IV synaptic
      contacts. This higher number of GABA contacts was not due to a greater density of
      GABA boutons, but to an increased number of contacts made by each layer IV GABA
      bouton (mean of 1.4 contacts per bouton compared to 1.1 in other cortical
      layers). The total area occupied by the contacts on an average GABA bouton was
      similar in all layers; the higher number of contacts per GABA bouton in layer IV
      being compensated for by their smaller size. This observed constancy in the area
      of synaptic contacts suggests the presence of one or more regulatory mechanisms
      maintaining optimal numbers of the different macromolecules forming the synaptic
      contacts. The increased density of GABA contacts in layer IV compared to other
      cortical layers was due to their greater number targeting distal regions of the
      dendritic tree. Since layer IV receives the vast majority of thalamocortical
      terminals and since these axons preferentially target dendritic spines, the
      specific arrangement of GABA synaptic contacts in this layer could be designed to
      exert a precise inhibition near the site of the thalamic input and thus serve as
      the structural basis for the strong GABA-related hyperpolarization that followed
      the excitatory response after physiological stimulations of the thalamocortical
      pathway.

PMID- 8144745
TI  - Light and electron microscopic analysis of synaptic development in Macaca monkey
      retina as detected by immunocytochemical labeling for the synaptic vesicle
      protein, SV2.
AB  - The development of synapses has been followed in Macaca monkey fetal and infant
      retina using immunocytochemical labeling for the transmembrane synaptic vesicle
      glycoprotein, SV2. Electron microscopy (EM) was used to verify the presence of
      morphological synapses at selected ages. EM immunocytochemical labeling in adult
      retina showed that all synaptic types contained SV2 in inner (IPL) and outer
      (OPL) plexiform layers. In fetal retina, SV2 expression and the appearance of
      morphological synapses were closely related in time, demonstrating that SV2 is a
      reliable marker for synaptogenesis. SV2 expression appears along a foveal to
      peripheral gradient. Both SV2 and synapses appear in the foveal IPL at Fd50-55,
      and reach the retinal edge by Fd90-103. Cone ribbon synapses and SV2 labeling are
      not present in the foveal OPL until Fd60. Photoreceptors in the far periphery
      contain SV2 by Fd119-125. This pattern demonstrates an "inner to outer" direction
      of synaptogenesis. Cones show SV2 labeling before rods at the same retinal
      eccentricity. In the cone-dominated fovea, SV2 labeling and bipolar cell ribbon
      containing terminals are present at Fd55 when amacrine cell conventional
      terminals are very scarce, indicating that bipolar synapses precede amacrine
      synapses in monkey foveal IPL. SV2 labeling and bipolar terminals appear first in
      the outer IPL which contains "OFF" ganglion and bipolar processes in the adult,
      suggesting that "OFF" midget bipolar cells may form the first synapses. Both SV2
      immunocytochemical labeling and EM morphology find that monkey retina follows a
      generalized inner before outer, and cone before rod synaptic developmental
      pattern, similar to that in other mammals. The cone-dominated fovea initiates
      synaptogenesis, and shows a different synaptic sequence from rod-dominated
      peripheral retina.

PMID- 8144747
TI  - Topography of neurons expressing luteinizing hormone-releasing hormone gene
      transcripts in the human hypothalamus and basal forebrain.
AB  - The distribution of neurons expressing luteinizing hormone-releasing hormone
      (LHRH) gene transcripts was mapped in the human hypothalamus and basal forebrain
      by in situ hybridization and computer-assisted microscopy. Hypothalamic blocks
      were dissected from five adult males and one adult female and snap frozen in
      isopentane. The blocks were serially sectioned either in the coronal or in the
      sagittal plane at a thickness of 20 microns. Approximately every twentieth
      section was incubated with a 35S-labeled cDNA probe complementary to LHRH mRNA.
      Specificity was confirmed by hybridization of adjacent sections with a probe
      targeted to the gonadotropin-associated protein (GAP) region of LHRH messenger
      ribonucleic acids (mRNA). Maps of neurons containing LHRH mRNA were manually
      digitized with the aid of an image-combining computer microscope system. We
      report a much wider distribution and greater numbers of LHRH neurons than have
      been previously described in the human brain. Three morphological subtypes were
      observed based on cell size and labeling density: 1) small, heavily labeled, oval
      or fusiform neurons, located primarily in the medial basal hypothalamus, ventral
      preoptic area, and periventricular zone; 2) small, oval, sparsely labeled neurons
      located in the septum and dorsal preoptic region and scattered from the bed
      nucleus of the stria terminalis to the amygdala ("extended amygdala"); and 3)
      large round neurons (> 500 microns 2 sectional profile area), intermediate in
      labeling density, scattered within the magnocellular basal forebrain complex,
      extended amygdala, ventral pallidum, and putamen. The pronounced differences in
      morphology, labeling density, and location of the three subtypes suggest that
      distinct functional subgroups of LHRH neurons exist in the human brain.

PMID- 8144748
TI  - Vestibulo-oculomotor connections in an elasmobranch fish, the Atlantic stingray,
      Dasyatis sabina.
AB  - In elasmobranch fishes, including the Atlantic stingray, the medial rectus muscle
      is innervated by the contralateral oculomotor nucleus. This is different from
      most vertebrates, in which the medial rectus is innervated by the ipsilateral
      oculomotor nucleus. This observation led to the prediction that the excitatory
      vestibulo-extraocular motoneuron projections connecting each semicircular canal
      to the appropriate muscle should use a contralateral projection from the
      vestibular nuclei to the motoneurons. This hypothesis was examined in the
      Atlantic stingray by injecting horseradish peroxidase unilaterally into the
      oculomotor nucleus. It was found that vestibulo-oculomotor projections arise from
      the ipsilateral anterior octaval nucleus and the contralateral descending octaval
      nucleus. The same pattern was observed when the trochlear nucleus was involved in
      the injection. There were no cells labeled in the region of the abducens nucleus,
      and no candidate for a nucleus prepositus hypoglossus was identified. The
      presence of compensatory eye movements, the directional sensitivity of the
      semicircular canals, the location of the motoneurons innervating each eye muscle,
      and our results indicate that the excitatory input to the extraocular motoneurons
      is derived from the contralateral descending octaval nucleus, and the inhibitory
      input is derived from the ipsilateral anterior octaval nucleus. The absence of
      both abducens internuclear interneurons and a nucleus prepositus hypoglossus
      suggests that eye movements, particularly those in the horizontal plane, are
      controlled differently in elasmobranchs than in other vertebrates examined to
      date.

PMID- 8144750
TI  - Context: the texture of nursing.

PMID- 8144749
TI  - Efficacy of Brahman breeding in the management of insecticide-resistant horn
      flies (Diptera: Muscidae) on beef cattle.
AB  - The efficacy of Brahman breeding used as an alternative tactic to manage
      insecticide-resistant populations of adult horn flies, Haematobia irritans
      irritans (L.), was determined. Concentration-mortality bioassays done at
      Booneville and Hope, AR, in 1988 and 1989, respectively, showed that horn fly
      populations were resistant to diazinon, pirimiphos methyl, tetrachlorvinphos, and
      methoxychlor. Data showed loss of field efficacy for coumaphos and delnav. Mean
      horn fly counts on Braham cows were significantly lower than on Angus cows for
      all sampling dates in 1989 and 1990. Mean fly counts on Brahman x Angus cows were
      approximately intermediate to the two purebred mean fly counts. Brahman breeding
      caused significant reductions in the number of organophosphate-resistant horn
      flies, which had been equal to or greater than that obtained from continued
      spraying with organophosphate insecticides. The Brahman x Hereford cows, which
      have one-eighth greater Brahman breeding than the Brangus cows, had fewer horn
      flies on 48 of 56 sampling dates in 1988-1990 and significantly fewer flies on 37
      sampling dates. The effectiveness of Brahman breeding in causing lower numbers of
      insecticide-resistant horn flies significantly increased as the percentage of
      Brahman breeding increased.

PMID- 8144751
TI  - Increasing minority participation in biomedical and nursing research.
AB  - There is an increased need for minority representation in biomedical and nursing
      research. Factors such as lack of suitable mentors, inadequate academic
      preparation, and poor self-image contribute to minorities not seeking graduate
      education and careers in research. This article presents an overview of a
      federally funded research project, Minority Biomedical Research Support (MBRS),
      that provided opportunities for Native Americans to participate in and gain
      experience with a research project. The project involved a qualitative study that
      investigated diabetes mellitus in the Navajo and Hopi peoples. Students were
      trained in all aspects of the research process including data collection and
      analysis and the preparation of final reports. Some of the perplexing issues and
      concerns that surround minority participation in research are discussed. MBRS
      programs can provide a model and means for nurse researchers to conduct
      worthwhile investigations and provide research training for minority students.
      The authors use their experience with this study to encourage more involvement by
      nursing programs in projects such as this, thus enhancing minority opportunities
      in nursing research.

PMID- 8144752
TI  - Good life, good death, and the right to die: ethical considerations for decisions
      at the end of life.
AB  - This article examines a range of ethically related concerns and considerations
      that must be addressed by health professionals and society as they grapple with
      how to make decisions about the type and degree of treatment to provide to
      patients at the ends of their lives. These considerations include (1) medical and
      nursing indications; (2) patient desires; (3) patient interests, including
      benefit/burden analysis and quality-of-life considerations; (4) family wishes and
      interests; and (5) costs. The article elaborates the ethical warrants and
      justifications for why these concerns need to be addressed in clinical decision
      making and in the development of a national health care policy. A substantial
      bibliography of current ethics literature on these issues is included.

PMID- 8144753
TI  - The uses of history--a Canadian case study.

PMID- 8144754
TI  - Looking through the constructivist lens: the art of creating nursing work groups.
AB  - Almost every facet of nursing requires some aspect of group work, and at some
      point in their career most nurse managers will organize or appoint a work group
      to carry out selected nursing activities. Group work can be challenging for
      members when work expectations are not clear. However, group outcomes can also be
      disappointing for the manager who appoints a group, if the group is unable to
      make decisions and accomplish the specified task or becomes enmeshed in
      tangential matters. Social constructivism, a recent addition to the family and
      group literature, provides a different perspective for understanding and
      facilitating group work. This article provides an overview of group work as seen
      through the lens of social constructivist thought. The intent of this article is
      to critique the linear paradigm that some managers use for appointing work
      groups, committees, and task forces, and to discuss constructivist-based
      approaches as more effective ways of promoting positive consensus, cohesion, and
      cooperation among nursing work groups.

PMID- 8144755
TI  - Alma-Ata, at last.

PMID- 8144756
TI  - Reporting of instrument validity and reliability in selected clinical nursing
      journals, 1989.
AB  - Before research findings are applied to practice, the quality of the research
      must be assessed so that flawed research does not lead inadvertently to flawed
      practice. Two critical indicators of research quality are the validity and
      reliability of the data collection instruments. This article summarizes the
      principles of instrument validity and reliability and identifies deviations from
      these principles in a random sample of 55 research studies published in 1989 in
      five refereed nursing journals targeted toward practicing clinicians. Using a
      valid and reliable instrument, the investigators found that even with a policy of
      giving authors "the benefit of the doubt," 47% of the research studies contained
      no evidence of validity for any data collection instruments and 36% had no
      evidence of reliability; 29% had no evidence of either validity or reliability.
      Content validity, a basic requirement for all research instruments, was addressed
      in only 27% of the studies. This article provides documentation, justification,
      and suggestions for nursing educators, journal editors, and researchers to take
      action to improve the reporting of instrument validity and reliability to help
      ensure the quality of the research on which nursing practice is based.

PMID- 8144757
TI  - Nursing and the euthanasia debate.

PMID- 8144758
TI  - A model for intervention and predicting success on the National Council Licensure
      Examination for Registered Nurses.
AB  - The purpose of this study was to examine the relationship of selected academic
      variables to National Council Licensure Examination for Registered Nurses (NCLEX
      RN) performance and determine a "best set" of indicators predictive of NCLEX-RN
      success. These variables could be used as early indicators of students at risk
      for failing the NCLEX-RN. The sample for this retrospective ex post facto study
      included 152 basic students who completed the baccalaureate nursing program
      between 1985 and 1987 at a large midwestern university. Data were analyzed by
      using multiple regression analysis to determine the strongest combination of
      variables predicting NCLEX-RN success. Pearson's Product Moment Correlation
      Coefficients were computed between interval level criterion and predictor
      variables. The best predictors were a sophomore nursing theory course (N205), a
      junior nursing theory course (N311), the junior year grade point average (JGPA),
      and a senior nursing theory course (N421). Results of this study indicated that
      selected nursing theory courses and the JGPA could be used in a statistical model
      to predict pass or fail on the NCLEX-RN.

PMID- 8144759
TI  - Culturally competent care and the school environment.

PMID- 8144760
TI  - Increasing minorities in higher education in nursing: faculty consultation as a
      strategy.
AB  - This article describes some of the issues surrounding cultural diversity in
      higher education in nursing. The representation of minority faculty in higher
      education in general, and in nursing education in particular, is inadequate to
      support the needs of students, faculties, and the institutions. Examples of
      common concerns and dilemmas faced by minority faculty demonstrate the urgent
      need for change to enhance the academic environment for minorities. Because the
      numbers of minority faculty in higher education are unlikely to change
      substantially within the next few years, the authors present faculty consultation
      as a strategy to support the cultural diversity mission of the college.

PMID- 8144761
TI  - Immediate coronary angioplasty versus intravenous streptokinase in acute
      myocardial infarction: left ventricular ejection fraction, hospital mortality and
      reinfarction.
AB  - OBJECTIVES: The purpose of the present study was to compare intravenous
      streptokinase therapy with immediate coronary angioplasty without antecedent
      thrombolytic therapy with regard to left ventricular function and hospital
      mortality and reinfarction. BACKGROUND: Despite the widespread use of intravenous
      thrombolytic therapy and immediate percutaneous transluminal coronary
      angioplasty, these two strategies to treat patients with an acute myocardial
      infarction have only recently been compared in randomized trials. Coronary
      angioplasty has been shown to result in a higher patency rate of the infarct
      related coronary artery, with a less severe residual stenotic lesion, compared
      with streptokinase therapy, but whether this more favorable coronary anatomy
      results in clinical benefit remains to be established. METHODS: We studied 301
      patients with acute myocardial infarction randomly assigned to undergo immediate
      coronary angioplasty without antecedent thrombolytic therapy or to receive
      intravenous streptokinase therapy. Before discharge left ventricular ejection
      fraction was measured by radionuclide scanning. RESULTS: The in-hospital
      mortality rate in the streptokinase group was 7% (11 of 149 patients) compared
      with 2% (3 of 152 patients) in the angioplasty group (p = 0.024). In the
      streptokinase group recurrent myocardial infarction occurred in 15 patients (10%)
      versus in 2 (1%) in the angioplasty group (p < 0.001). Either death or nonfatal
      reinfarction occurred in 23 patients (15%) in the streptokinase group and in 5
      patients (3%) in the angioplasty group (p = 0.001). Left ventricular ejection
      fraction was 44 +/- 11% (mean +/- SD) in the streptokinase group versus 50 +/-
      11% in the angioplasty group (p < 0.001). CONCLUSIONS: These findings indicate
      that immediate coronary angioplasty without antecedent thrombolytic therapy
      results in better left ventricular function and lower risk of death and recurrent
      myocardial infarction than treatment with intravenous streptokinase.

PMID- 8144762
TI  - Rapid diagnosis of coronary reperfusion by measurement of myoglobin level every
      15 min in acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to examine whether coronary reperfusion
      can be diagnosed rapidly and accurately by myoglobin measurements. BACKGROUND:
      When intravenous thrombolysis is used for acute myocardial infarction, it is
      important to determine coronary reperfusion rapidly and noninvasively so that
      further treatment can be initiated. METHODS: We determined myoglobin, creatine
      kinase (CK) and creatine kinase, MB fraction (CK-MB) isoenzyme levels in 63
      patients with acute myocardial infarction with total occlusion of the infarct
      related artery that was confirmed by coronary angiography. Myoglobin was measured
      by turbidimetric latex agglutination, which has an assay time of 10 min. We
      measured myoglobin, CK and CK-MB every 15 min in 45 patients with and 18 patients
      without reperfusion. The condition of the infarct-related artery was confirmed
      every 5 to 8 min by coronary angiography. RESULTS: The rate of increase in
      myoglobin, CK, and CK-MB at 15, 30, 45 and 60 min after treatment and reperfusion
      was significantly higher in the reperfused than in the nonreperfused group. In
      the reperfused group, the rate of increase in myoglobin was significantly higher
      than the corresponding rate of increase in CK and CK-MB at 15, 30 and 45 min
      after reperfusion. When reperfusion was evaluated on the basis of a cutoff level
      (myoglobin > or = 2.0, CK > or = 1.8, CK-MB > or = 1.5), the predictive accuracy
      of myoglobin (95%) was significantly higher than that of CK (68%) and CK-MB (73%)
      at 15 min after reperfusion. CONCLUSIONS: Coronary reperfusion can be rapidly and
      accurately detected by measurement of the plasma myoglobin every 15 min.

PMID- 8144763
TI  - Technetium-99m sestamibi myocardial perfusion imaging in the emergency room
      evaluation of chest pain.
AB  - OBJECTIVES: The purpose of this investigation was to evaluate the practicality
      and short-term predictive value of acute myocardial perfusion imaging with
      technetium-99m sestamibi in emergency room patients with typical angina and a
      normal or nondiagnostic electrocardiogram (ECG). BACKGROUND: Accuracy of
      emergency room chest pain assessment may be improved when clinical and ECG
      variables are used in conjunction with acute thallium-201 myocardial perfusion
      imaging. Technetium-99m sestamibi is a new radioisotope that is taken up by the
      myocardium in proportion to blood flow, but unlike thallium-201, it redistributes
      minimally after injection. Technetium-99m sestamibi can thus be injected during
      chest pain, and images acquired 1 to 2 h later (when patients have been
      clinically stabilized) will confirm whether abnormalities of perfusion were
      present at the time of injection. METHODS: One hundred two emergency room
      patients with typical angina (on the basis of a standardized angina
      questionnaire) and a normal or nondiagnostic ECG had a technetium-99m sestamibi
      injection during symptoms and were followed up for occurrence of adverse cardiac
      events (cardiac death, nonfatal myocardial infarction, coronary angioplasty,
      coronary surgery or coronary thrombolysis). RESULTS: Univariate predictors of
      cardiac events included the presence of three or more coronary risk factors (p =
      0.009, risk ratio 3.3) and an abnormal or equivocal acute technetium-99m
      sestamibi scan (p = 0.0001, risk ratio 13.9). Multivariate regression analysis
      identified an abnormal perfusion image as the only independent predictor of
      adverse cardiac events (p = 0.009). Of 70 patients with a normal perfusion scan,
      only 1 had a cardiac event compared with 15 patients with equivocal scans or 17
      patients with abnormal scans, with a cardiac event rate of 13% and 71%,
      respectively (p = 0.0004). CONCLUSIONS: Initial myocardial perfusion imaging with
      technetium-99m sestamibi when applied in emergency room patients with typical
      angina and a normal or nondiagnostic ECG appears to be highly accurate in
      distinguishing between low and high risk subjects.

PMID- 8144764
TI  - Cyclic flow variations after coronary angioplasty in humans: clinical and
      angiographic characteristics and elimination with 7E3 monoclonal antiplatelet
      antibody.
AB  - OBJECTIVES: We tested the hypothesis that cyclic alterations in coronary artery
      blood flow that occurred after coronary angioplasty could be attenuated or
      abolished by a monoclonal antibody to the platelet surface membrane GP IIb/IIIa
      receptor. BACKGROUND: Coronary artery cyclic flow variations may occur after
      coronary angioplasty in experimental animal models and humans. In animal models
      of coronary thrombosis, cyclic alterations in flow often have preceded thrombotic
      occlusion or reocclusion. Several agents that inhibit platelet function have been
      shown to attenuate or eliminate cyclic flow variations in these models. METHODS:
      We monitored coronary artery flow in 27 patients for 30 min after coronary
      angioplasty, using 0.018-in. (0.046 cm) coronary guide wires with pulsed wave
      Doppler ultrasound transducers on the distal tips. Clinical data were collected
      and quantitative analyses performed on coronary arteriograms made before and
      after the angioplasty procedures. We compared findings in patients with and
      without cyclic flow variations detected. RESULTS: There were 20 men and 7 women.
      Mean age was 58 years, and 63% had unstable angina. They received standard doses
      of nitrates, aspirin, heparin, calcium channel antagonists and other medications
      clinically indicated. Nevertheless, we detected cyclic flow variations in five
      patients (19%). Four of these patients had stable flow restored with intravenous
      injection of 0.25 mg/kg normal body weight of monoclonal antibody c7E3 Fab to the
      platelet GP IIb/IIIa receptor. In one patient, stable flow was restored by repeat
      dilation when an immediate angiogram revealed renarrowing. Patients developing
      cyclic alterations in flow had longer lesions (18.7 +/- 7.5 mm vs. 13.1 +/- 5.7
      mm, p < 0.05) that had responded less well to angioplasty (stenosis
      postangioplasty 47 +/- 13% vs. 33 +/- 15%, p < 0.05). CONCLUSIONS: Cyclic
      alterations in coronary artery blood flow may occur in some patients after
      coronary angioplasty, despite the use of standard antiplatelet, antithrombotic
      and antivasospastic medications. We found that they could be eliminated by this
      monoclonal antibody that blocks the final common event of platelet aggregation.

PMID- 8144765
TI  - Initial and long-term outcome of 83 patients after balloon angioplasty of totally
      occluded bypass grafts.
AB  - OBJECTIVES: This study was designed to evaluate the safety and short- and long
      term results of coronary angioplasty of totally occluded bypass grafts in
      patients with clinical conditions other than acute myocardial infarction.
      BACKGROUND: Total occlusion of bypass grafts after coronary artery surgery often
      causes recurrent ischemia. The safety and results of percutaneous transluminal
      coronary angioplasty in occluded bypass grafts are controversial. METHODS: All
      patients with dilation of a totally occluded bypass graft attempted between 1981
      and 1991 were retrospectively identified from a data base. Patients treated in
      the setting of an acute myocardial infarction were excluded. Eighty-three
      patients met these criteria and constitute the study group. Hospital records,
      office charts and procedural reports were reviewed in all patients to supplement
      details available in the data base. RESULTS: The time from bypass surgery to
      attempted coronary angioplasty ranged from 1 to 226 months (mean time 88 months).
      The mean (+/- SD) duration of graft occlusion was 31 +/- 46 days (range 1 to
      180). In 27 attempts the bypass graft was the only site dilated, and in 56
      attempts (68%) one to six other sites (n = 101) were dilated. Angiographic
      success (< or = 40% residual lumen stenosis) was achieved in 61 grafts (73%) and
      98 of the additional sites (97%) (p < 0.001). Major complications included one
      procedural death and two Q wave infarctions. Follow-up for a mean of 32 months
      demonstrated a 1- and 3-year actuarial survival rate of 94% and 80%,
      respectively. At 3 years, only 34% of patients were free of repeat angioplasty or
      surgery. CONCLUSIONS: Angioplasty of totally occluded bypass grafts can be
      successful in the majority of selected patients, although major complications can
      occur. Strategies for sustained patency are needed to improve the long-term
      results.

PMID- 8144766
TI  - Balloon angioplasty results in increased segmental coronary distensibility: a
      likely mechanism of percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVES: The purpose of this study was to evaluate the hypothesis that the
      increase in lumen area induced by percutaneous transluminal coronary angioplasty
      is secondary to a change in lesion (segmental) distensibility. BACKGROUND:
      Despite the widespread use of coronary angioplasty, the precise mechanism (or
      mechanisms) of lumen area improvement remains poorly understood. METHODS:
      Quantitative coronary angiography was used to measure the minimal (contrast agent
      filled) balloon diameters at 1 to 5 atm, inclusive, during the first and final
      balloon inflations in 24 lesions successfully treated with coronary angioplasty.
      To rule out possible confounding effects due to changes in balloon material
      distensibility during repeated inflations, five control balloons were studied ex
      vivo. In parallel, intravascular ultrasound imaging was utilized to compare the
      segmental distensibility (change in lumen area during the cardiac cycle) of eight
      disease-free and seven mildly diseased coronary segments and seven segments after
      successful balloon angioplasty. RESULTS: Minimal balloon diameters increased
      significantly between the first and final inflations (46%, 33%, 26%, 14% and 10%
      at 1, 2, 3, 4 and 5 atm, respectively, all p < 0.0001), demonstrating an increase
      in arterial distensibility after successful coronary angioplasty. No significant
      changes in balloon diameters were observed during sequential initial inflations
      at 1 and 2 atm (n = 5). Minimal increases in balloon diameters were observed
      during repeated balloon inflations in the ex vivo studies (4.9 +/- 1% [mean +/-
      SEM]). A distensibility index, derived from the intravascular ultrasound data,
      was not different between the balloon-dilated and the normal segments but was
      significantly lower in mildly diseased sites (14.7 +/- 2.2 vs. 12.9 +/- 1.2 vs.
      6.9 +/- 1.9, respectively, p < 0.05) despite a smaller plaque area (7.3 +/- 1 vs.
      11.3 +/- 1 mm2, proximal/nondilated vs. dilated segments, respectively, p <
      0.05). CONCLUSIONS: Coronary distensibility is significantly impaired in
      atherosclerotically diseased coronary segments and increases significantly after
      balloon angioplasty. This increase in segmental coronary compliance after
      coronary angioplasty may create a larger lumen area by allowing the vessel to
      distend in response to normal intraarterial pressure.

PMID- 8144767
TI  - Emergency coronary stenting for dissection during percutaneous transluminal
      coronary angioplasty: angiographic follow-up after stenting and after repeat
      angioplasty of the stented segment.
AB  - OBJECTIVES: The purpose of this study was to assess the angiographic results
      after emergency coronary stenting and after repeat angioplasty for restenosis
      within the stent. BACKGROUND: There is still little angiographic information
      about lumen renarrowing and its correlates after emergency stenting, and data
      with regard to the angiographic outcome of repeat angioplasty within the stent
      are almost nonexistent. METHODS: This study was based on the quantitative
      evaluation of angiograms performed before and immediately after intervention and
      at 6-month follow-up. The study included 164 of the 183 eligible patients with
      emergency Palmaz-Schatz stent implantation and 31 of those with restenosis within
      the stent who had repeat angioplasty. RESULTS: Stenting produced an improvement
      in minimal lumen diameter from 0.82 +/- 0.41 to 2.76 +/- 0.47 mm (mean +/- SD)
      and in diameter stenosis from 74.9 +/- 11.5% to 18.3 +/- 8.1%. Elastic recoil was
      0.51 +/- 0.34 mm, or 16%. At 6-month follow-up, 32.3% of the patients had
      restenosis (> or = 50% stenosis). Minimal lumen diameter decreased to 1.84 +/-
      0.78 mm, and diameter stenosis increased to 41.7 +/- 21.0%. The degree of lumen
      loss correlated significantly with the length of the original stenosis and the
      initial lumen gain achieved by stenting. Thirty-one patients with in-stent
      restenosis underwent repeat angioplasty. The primary success rate was 100%, and
      no abrupt vessel closure was verified. Minimal lumen diameter increased from 0.85
      +/- 0.35 to 2.18 +/- 0.39 mm, and diameter stenosis decreased from 69.7 +/- 12.9%
      to 28.6 +/- 9.4%. Elastic recoil was 0.82 +/- 0.38 mm, or 27%. At follow-up,
      38.5% of the patients had restenosis. Minimal lumen diameter was reduced to 1.72
      +/- 0.67 mm, and diameter stenosis increased to 42.4 +/- 18.1%. CONCLUSIONS:
      Angiographic results of emergency coronary stenting compare favorably with those
      of conventional angioplasty. In-stent balloon redilation in patients with
      restenosis is associated with excellent short-term results and a restenosis rate
      not different from that reported for nonstented vessels.

PMID- 8144768
TI  - Relation between procedural activated coagulation time and outcome after
      percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVES: The purpose of this study was to determine whether a low procedural
      activated coagulation time is associated with a high rate of in-hospital
      complications and to identify whether there is an activated coagulation time
      range that may be associated with a low rate of complications. BACKGROUND: In
      recent years the activated coagulation time has come into widespread use for
      monitoring anticoagulation in the catheterization laboratory. However,
      considerable controversy exists as to the standards by which to judge "adequate"
      anticoagulation for interventional procedures. METHODS: From a total of 1,469
      consecutive patients with percutaneous transluminal coronary angioplasty, we
      retrospectively identified 103 (Group I, 7% of the overall population) with major
      complications of death or emergency or urgent coronary artery bypass graft
      surgery and compared them with 400 patients without complications (Group II).
      Group I patients had more high risk clinical characteristics, such as type B and
      C lesions, class III and IV angina, recent myocardial infarction and recent
      thrombolytic treatment. Activated coagulation times were compared between Groups
      I and II at baseline, after administration of 10,000 U of heparin and at the end
      of the procedure. RESULTS: There were no differences in baseline activated
      coagulation times between Groups I and II. Group I had significantly lower
      activated coagulation times after heparin therapy and at the end of the
      procedure: 61% < 250 s, 20% between 250 and 275 s, 11% between 275 and 300 s and
      8% > 300 s; 279 of Group II had activated coagulation times 27% < 250 s, 17%
      between 250 and 275 s, 35% between 275 and 300 s and 21% > 300 s (p < 0.0001).
      Complications occurred in all patients with final activated coagulation times <
      250 s but in only 0.3% of patients with final activated coagulation times > 300
      s. CONCLUSIONS: A diminished activated coagulation time response to an initial
      bolus of heparin is associated with major in-hospital complications after
      coronary angioplasty, although patients with complications did have a higher risk
      before the procedure. It remains to be determined whether there is an ideal
      "target" activated coagulation time for interventional procedures.

PMID- 8144769
TI  - Percutaneous transluminal angioplasty of saphenous vein grafts for medically
      refractory unstable angina.
AB  - OBJECTIVES: We attempted to answer the question, Is balloon angioplasty a
      reasonable alternative to repeat coronary artery bypass graft surgery in patients
      with previous coronary bypass graft surgery, medically refractory unstable angina
      and vein graft lesions? BACKGROUND: Patients with medically refractory unstable
      angina need revascularization. Patients with previous coronary artery bypass
      graft surgery and medically refractory angina are at "high risk" for adverse
      outcomes with repeat coronary bypass graft surgery. Conversely, patients with
      angioplasty of old vein grafts are also at "high risk" for adverse outcomes.
      METHODS: Balloon angioplasty of 89 lesions in saphenous vein grafts was performed
      in 75 consecutive patients with medically refractory unstable angina. Of these 75
      patients, 24 (32%) had myocardial infarct within 30 days, 23 (31%) had left
      ventricular ejection fraction < 0.35, and 50 (67%) had major comorbidity.
      Patients underwent standard balloon angioplasty with aggressive use of
      intravenous and intracoronary heparin, urokinase, nitroglycerin, oral aspirin,
      calcium channel blocking agents and coumadin. RESULTS: Angiographic success
      (reduction of stenosis < or = 50% without major complication) was seen in 84 of
      89 lesions. Clinical success (angiographic success plus hospital discharge
      without major complication) was seen in 70 of 75 patients. During index
      hospitalization, two patients (3%) died, two (3%) had nonfatal infarcts, and one
      (1%) had emergency reoperation (coronary bypass graft surgery). In late follow up
      (3 to 66 months), 14 (20%) patients were lost to follow-up, 17 (23%) had repeat
      percutaneous transluminal coronary angioplasty, 2 (3%) had late bypass graft
      reoperation, 18 (25%) had late death, and 1 (< 1%) had a heart transplant. Of the
      41 patients alive after one or more angioplasties, 25 have little or no angina,
      and 16 have occasional or more angina. We compared long-term survival rate in
      these 75 patients with a cohort of patients with high risk, unstable angina from
      the Veterans Affairs Surgical Registry (2,570 patients). The 30-day survival rate
      was better in patients with coronary angioplasty (97% vs. 92%, p < 0.05), but by
      6 months there was no difference, and by 5 years a trend toward a higher survival
      rate with coronary artery bypass graft surgery was seen. CONCLUSIONS: Balloon
      angioplasty of saphenous vein grafts with aggressive adjunctive pharmacotherapy
      is a reasonable alternative to repeat coronary bypass graft surgery in patients
      with medically refractory unstable angina, previous coronary bypass graft surgery
      and saphenous vein narrowing.

PMID- 8144770
TI  - The role of percutaneous aortic balloon valvuloplasty in patients with
      cardiogenic shock and critical aortic stenosis.
AB  - OBJECTIVES: The goal of this study was to evaluate the role of percutaneous
      aortic valvuloplasty in patients with cardiogenic shock due to severe aortic
      stenosis and associated major comorbid conditions and to establish predictors of
      survival. BACKGROUND: The prognosis for patients in cardiogenic shock with severe
      aortic stenosis is poor. Aortic valve replacement can be lifesaving, but the
      presence of multiorgan failure precludes these patients from operation.
      Percutaneous aortic balloon valvuloplasty has been used in these patients with
      short-term improvement and could be an alternative therapeutic option. METHODS:
      Of 310 patients undergoing percutaneous aortic balloon valvuloplasty, 21 were in
      cardiogenic shock and were included in this study. All 21 patients had associated
      major comorbid conditions at the time of presentation. RESULTS: After
      percutaneous aortic balloon valvuloplasty, systolic aortic pressure increased
      from 77 +/- 3 (mean +/- SEM) to 116 +/- 8 mm Hg (p = 0.0001); aortic valve area
      increased from 0.48 +/- 0.04 to 0.84 +/- 0.06 cm2 (p = 0.0001); and cardiac index
      increased from 1.84 +/- 0.13 to 2.24 +/- 0.15 liters/min per m2 (p = 0.06). Nine
      patients died in the hospital, two during the procedure and seven after
      successful percutaneous aortic balloon valvuloplasty (five from multiorgan
      failure). Five patients had vascular complications. Stroke, cholesterol emboli
      and aortic regurgitation requiring aortic valve replacement occurred in one
      patient each. Twelve patients (57%) survived and were followed up for 15 +/- 6
      months; five patients subsequently died. The Kaplan-Meier survival curve showed a
      38 +/- 11% survival rate at 27 months. The only predictor for longer survival
      rate was the postprocedure cardiac index. CONCLUSIONS: 1) Emergency percutaneous
      aortic balloon valvuloplasty can be performed successfully as a lifesaving
      procedure. 2) Morbidity and mortality remain high despite successful percutaneous
      aortic balloon valvuloplasty. 3) For nonsurgical candidates, percutaneous aortic
      balloon valvuloplasty may be the only therapeutic alternative.

PMID- 8144771
TI  - Catheter balloon valvuloplasty for severe calcific aortic stenosis: a limited
      role.

PMID- 8144772
TI  - Composition of coronary atherosclerotic plaque in the intima and media affects
      intravascular ultrasound measurements of intimal thickness.
AB  - OBJECTIVES: The purpose of this study was to evaluate how intravascular
      ultrasound-determined thickness and reflectivity of the inner echogenic layer of
      coronary artery plaque is affected by changes in collagen, elastin, proteoglycan,
      calcium and lipid content in the intima and media. BACKGROUND: Coronary artery
      plaque often results in disruption of the internal elastic lamina and in
      increased collagen in the media as well as increased intimal lipid, calcium and
      proteoglycan content. How these factors affect intravascular ultrasound-derived
      measurements of intimal thickness are unknown. METHODS: Twenty-one coronary
      artery segments from 10 patients with varying degrees of coronary artery disease
      were obtained fresh and unfixed at autopsy. Intravascular ultrasound (30-MHz,
      3.5F catheter) was performed at regions in the vessel where a three-layered
      region was evident. Quantitative measurements of inner echogenic and deeper
      echolucent layer thickness were determined as well as estimates of ultrasound
      reflectivity and compared with histologic measurements of intimal and medial
      thickness and collagen, proteoglycan, lipid and calcium content. RESULTS: In
      plaque > 300 microns thick and equivalent histologic levels of collagen, inner
      echogenic layer reflectivity was greater in regions with a greater amount of
      calcium and proteoglycan and lesser amounts of lipid. Inner echogenic layer
      thickness correlated well with intimal thickness but had the best correlation
      with intimal and medial thickness when medial collagen content was increased (r =
      0.89). The median observed difference between intimal and inner echogenic
      thickness was 160 (p < 0.05 compared with zero), whereas the median observed
      difference between inner echogenic thickness and intimal plus medial thickness
      when medial collagen content was increased was 60 (not significantly different
      from zero). CONCLUSIONS: The inner echogenic layer of human coronary artery
      plaque may represent both intima and media. The echolucent layer by ultrasound
      may represent only the basal section of the media that does not contain high
      collagen content.

PMID- 8144773
TI  - High risk for vascular events in patients with protruding aortic atheromas: a
      prospective study.
AB  - OBJECTIVES: The purpose of this study was to prospectively evaluate the risk of
      vascular events in patients with protruding aortic atheromas. BACKGROUND:
      Protruding atheromas of the thoracic aorta have been shown to be associated with
      embolic disease in previous retrospective studies. METHODS: During a 1-year
      period, 521 patients had transesophageal echocardiography. Of these, 42 patients
      had protruding atheromas and no other source of emboli. They were followed up for
      up to 2 years (mean follow-up 14 months) and compared with a control group
      without atheromas, matched for age, gender and hypertension. RESULTS: Of 42
      patients with atheromas, 14 (33%) had 19 vascular events during follow-up (5
      brain, 2 eye, 4 kidney, 1 bowel, 7 lower extremity). Of 42 control patients, 3
      (7%) had vascular events (2 brain, 1 eye). Univariate analysis identified only
      protruding atheromas as significantly correlating with events (p = 0.003). There
      was no positive correlation of events with age, gender, hypertension, smoking,
      family history, atrial fibrillation, valve replacement, antithrombotic drug use,
      diabetes or coronary disease. Multivariate analysis showed that only protruding
      atheromas independently predicted events (p = 0.005, odds ratio 4.3, 95%
      confidence interval 1.2 to 15.0). Nine patients died in the atheroma group versus
      six in the control group, but this was not statistically significant (p = 0.39).
      CONCLUSIONS: Protruding atheromas seen on transesophageal echocardiography
      predict future vascular events.

PMID- 8144774
TI  - Long-term survival in patients with coronary artery disease: importance of
      peripheral vascular disease. The Coronary Artery Surgery Study (CASS)
      Investigators.
AB  - OBJECTIVES: The purpose of this study was to determine the importance of
      peripheral arterial disease in predicting long-term survival in patients with
      clinically evident coronary artery disease. BACKGROUND: Patients in the Coronary
      Artery Surgery Study (CASS) Registry were followed up for > 10 years. METHODS:
      Survival in 2,296 patients with peripheral arterial disease was compared with
      that of 13,953 patients without peripheral arterial disease using Kaplan-Meier
      survival curves. All patients had known stable coronary artery disease. Clinical,
      electrocardiographic (ECG), chest X-ray film and catheterization variables of the
      two groups were compared using the chi-square statistic or the two-sample t test.
      The independent effect of peripheral arterial disease (as well as other
      variables) on mortality was determined utilizing a Cox proportional hazards
      model. RESULTS: Patients with peripheral vascular disease were more likely to
      have hypertension, diabetes, family history of coronary artery disease, previous
      angina or myocardial infarction, previous coronary bypass surgery or to have
      smoked. They also had a higher incidence of congestive heart failure, ECG
      abnormality and modestly increased frequency of three-vessel disease. Independent
      correlates of long-term mortality for the entire cohort included age, smoking,
      diabetes, number of diseased coronary vessels, left ventricular function,
      hypertension, pulmonary disease, anginal class, previous myocardial infarction
      and peripheral vascular disease (all p < 0.001). At any point in time, patients
      with peripheral vascular disease had a 25% greater likelihood of mortality than
      patients without peripheral vascular disease (multivariate chi-square 25.83,
      hazard ratio 1.25, 95% confidence interval 1.15 to 1.36, p < 0.001). CONCLUSIONS:
      Peripheral vascular disease is a strong, independent predictor of long-term
      mortality in patients with stable coronary artery disease. Aggressive attempts at
      secondary disease prevention are warranted in this high risk group.

PMID- 8144775
TI  - Prognostic value of thallium-201 single-photon emission computed tomographic
      myocardial perfusion imaging according to extent of myocardial defect. Study in
      1,926 patients with follow-up at 33 months.
AB  - OBJECTIVES: This study was designed to assess the prognostic value of thallium
      201 single-photon emission computed tomographic (thallium SPECT) perfusion
      imaging in patients evaluated for stable angina pectoris and to examine the
      relation, if any, between the presence and extent of myocardial defect and future
      fatal or nonfatal cardiovascular events (revascularization, secondary myocardial
      infarction). BACKGROUND: Compared with planar scintigraphy, thallium SPECT
      enables better evaluation of the extent of myocardial perfusion defect. However,
      its prognostic value has not yet been studied in a large population of patients.
      METHODS: Between 1987 and 1989 we studied 3,193 patients. After exclusion of
      patients with unstable angina, myocardial infarction during the previous month or
      earlier revascularization, 1,926 patients were followed up for 33 +/- 10 (mean +/
      SD) months after stress thallium SPECT imaging (performed after exercise in
      1,121 patients or during dipyridamole infusion in 805 patients). Thallium SPECT
      imaging of the left ventricle was divided into six segments. RESULTS: After
      normal thallium SPECT imaging (715 patients), the annual total and cardiovascular
      mortality rates were, respectively, 0.42%/year and 0.10%/year and were
      significantly higher after abnormal thallium SPECT imaging (respectively, 2.1%,
      relative risk 5, p = 0.012; 1.5%, relative risk 15, p < 0.0001 [log-rank test]).
      There was a significant relation between the number of abnormal segments and
      cardiovascular mortality during follow-up (p < 0.02) or the occurrence of
      nonfatal events (p < 0.001). The extent of defect on the initial scan provided
      the best SPECT variable for long-term prognosis. Thallium SPECT imaging provided
      additive prognostic information compared with other clinical variables (gender,
      previous myocardial infarction) and exercise electrocardiogram. CONCLUSIONS: In
      patients with stable angina, normal thallium SPECT imaging indicates a low risk
      patient, and the extent of myocardial defect is an important prognostic
      predictive factor.

PMID- 8144776
TI  - Gated technetium-99m sestamibi for simultaneous assessment of stress myocardial
      perfusion, postexercise regional ventricular function and myocardial viability.
      Correlation with echocardiography and rest thallium-201 scintigraphy.
AB  - OBJECTIVES: This study compares technetium-99m sestamibi (sestamibi)
      electrocardiographic (ECG) gated single-photon emission computed tomography
      (gated SPECT) and echocardiography for the evaluation of myocardial function and
      assesses the feasibility of single-injection, single-acquisition stress
      perfusion/rest function technetium-99m sestamibi-gated SPECT as an alternative to
      conventional stress/rest imaging for assessment of myocardial perfusion and
      viability. BACKGROUND: Simultaneous assessment of stress perfusion and rest
      function is possible with gated SPECT acquisition of stress-injected technetium
      99m sestamibi. METHODS: Rest thallium-201 SPECT followed by stress sestamibi
      gated SPECT (acquired 0.5 to 1 h after sestamibi injection) was performed in 58
      patients. Echocardiography was performed immediately after or before gated SPECT
      in 43 of the patients. All studies were analyzed by semiquantitative visual
      scoring. Sestamibi-gated SPECT studies were read for stress perfusion and rest
      wall motion and thickening. Reversibility on sestamibi-gated SPECT was defined as
      the presence of a definite stress defect with normal or mildly impaired wall
      motion or thickening on gated SPECT: RESULTS: There was high segmental score
      agreement between gated SPECT and echocardiography for wall motion (91%, kappa =
      0.68, p < 0.001) and thickening (90%, kappa = 0.62, p < 0.001). Correlation for
      global wall motion (r = 0.98, p < 0.001) and thickening (r = 0.96, p < 0.001)
      scores between the two modalities was excellent. In 32 patients without previous
      myocardial infarction, there was excellent agreement for reversibility between
      stress sestamibi-gated SPECT and rest thallium-201/stress sestamibi (98%, kappa =
      0.93, p < 0.01). However, in 26 patients with previous infarction, discordance
      between the two approaches was frequent, with 26% (20 of 78) of nonreversible
      defects by stress sestamibi-gated SPECT being reversible by rest thallium
      201/stress sestamibi and 21% (23 of 112) of reversible defects by stress
      sestamibi-gated SPECT being nonreversible by rest thallium-201/stress sestamibi.
      CONCLUSIONS: Gated SPECT of stress-injected sestamibi correlates well with
      echocardiographic assessment of regional function and thus adds information to
      perfusion SPECT: In patients without previous myocardial infarction, a single
      injection stress perfusion/rest function approach using sestamibi-gated SPECT can
      substitute for conventional stress/rest myocardial perfusion imaging, adding a
      rest perfusion study only if there are nonreversible defects or consideration of
      attenuation artifacts. In patients with previous myocardial infarction, the gated
      SPECT approach does not replace the need for a rest perfusion study.

PMID- 8144777
TI  - Dipyridamole-dobutamine echocardiography: a novel test for the detection of
      milder forms of coronary artery disease.
AB  - OBJECTIVES: This study was designed to assess the clinical, hemodynamic and
      diagnostic effects of the addition of dobutamine to dipyridamole
      echocardiography. BACKGROUND: Pharmacologic stress echocardiography with either
      dipyridamole or dobutamine has gained acceptance because of its safety,
      feasibility, diagnostic accuracy and prognostic power. The main limitation of the
      two tests is a less than ideal sensitivity in some patient subsets, such as those
      with limited coronary artery disease. We hypothesized that two pharmacologic
      stresses might act synergistically in the induction of ischemia by combining the
      mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an
      increase in myocardial oxygen consumption (with dobutamine). METHODS: One hundred
      fifty patients (mean [+/- SD] age 51 +/- 11 years) referred for stress
      echocardiography were initially studied by dipyridamole-dobutamine
      echocardiography. The test was stopped during the dipyridamole step in 95
      patients for achievement of a predetermined end point (obvious dyssynergy induced
      by lower or higher dipyridamole dose), and dipyridamole-dobutamine tests were
      performed in 55 patients (negative dipyridamole echocardiographic test). In the
      same 150 patients the dobutamine echocardiographic test (up to 40 micrograms/kg
      body weight per min) was performed on a separate day. RESULTS: Significant
      coronary artery disease (> 50% diameter stenosis of at least one major coronary
      vessel by quantitative coronary arteriography) was present in 131 patients (one
      vessel in 115; two vessels in 10, three vessels in 6), with normal coronary
      arteriography in 19. The feasibility of the dipyridamole-dobutamine test was 96%.
      Self-limiting side effects occurred in 5% of patients. The peak rate-pressure
      product was lowest during the dipyridamole test (132 +/- 30) and was comparable
      during the dobutamine (186 +/- 59) and dipyridamole-dobutamine tests (179 +/- 45,
      p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for
      dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine
      echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine
      vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS),
      whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for
      dipyridamole-dobutamine echocardiography (p = NS for all). CONCLUSIONS: Routine
      dobutamine addition to dipyridamole stress testing is clinically useful and well
      tolerated. It expands the spectrum of the disease detectable by pharmacologic
      stress echocardiography and allows documentation of milder forms of coronary
      artery disease that can be missed by conventional dipyridamole or dobutamine
      stress echocardiography.

PMID- 8144778
TI  - Racial differences in myocardial ischemia and coronary flow reserve in
      hypertension.
AB  - OBJECTIVES: Using invasive measurements of endothelium-independent coronary flow
      reserve and stress thallium testing with or without dipyridamole, this study
      investigated racial differences in ischemia and coronary reserve in hypertensive
      left ventricular hypertrophy. BACKGROUND: African Americans compared with
      Caucasian Americans appear to have a higher case fatality from coronary heart
      disease but lesser amounts of atherosclerotic coronary artery disease. This
      paradox may be explainable by intrinsic or acquired racial differences in
      coronary arteriolar autoregulation and vasoreactivity. METHODS: The study
      enrolled 91 African and 81 Caucasian Americans referred for cardiac
      catheterization because of suspected myocardial ischemia but found to have no
      significant coronary stenosis. Patients were stratified by degree of left
      ventricular hypertrophy for comparison purposes after calculation of indexed left
      ventricular mass by means of echocardiographic M-mode measurements. Coronary flow
      reserve measurements were made using the intracoronary Doppler catheter and
      hyperemic doses of intravenous dipyridamole in 100 patients and intracoronary
      papaverine and adenosine in 72 patients. Seventy-seven percent of patients
      underwent adequate stress thallium testing with or without dipyridamole. RESULTS:
      In African Americans, mean (+/- SD) coronary flow reserve decreased from 4.4 +/-
      2.3 for 38 without mass hypertrophy to 3.2 +/- 1.3 for 53 with hypertrophy (p =
      0.005) to 2.7 +/- 1.1 for 12 with severe hypertrophy (p = 0.02). Thallium testing
      was abnormal in 31% of those without mass hypertrophy and 59% of those with
      hypertrophy. In Caucasian Americans, coronary flow reserve decreased from 4.1 +/-
      2 for 58 without hypertrophy to 3.6 +/- 1.5 for 23 with hypertrophy (p = NS) to 3
      +/- 1.5 for 6 with severe hypertrophy (p = NS). Thallium testing was abnormal in
      36% without mass hypertrophy and in 39% with hypertrophy. CONCLUSIONS: This study
      establishes that development of left ventricular hypertrophy in hypertension
      carries greater physiologic morbidity for African compared with Caucasian
      Americans, typified by marked reduction in endothelium-independent coronary flow
      reserve and increased frequency of abnormal thallium tests.

PMID- 8144779
TI  - New insights into the definition and meaning of proarrhythmia during initiation
      of antiarrhythmic drug therapy from the Cardiac Arrhythmia Suppression Trial and
      its pilot study. The CAST and CAPS Investigators.
AB  - OBJECTIVES: This study was undertaken to determine the characteristics of
      worsening ventricular arrhythmia during antiarrhythmic drug titration.
      BACKGROUND: Proarrhythmia is an evolving concept in cardiology. Its definition,
      incidence and clinical significance in various patient settings require
      refinement. METHODS: The impact of early proarrhythmia was analyzed in 3,840
      patients in the Cardiac Arrhythmia Suppression Trial (CAST). RESULTS: Drug
      therapy did not affect the incidence of new, sustained but nonfatal ventricular
      tachycardia (placebo 0.5%, active drug 0.4%). Nevertheless, there was a threefold
      increase in arrhythmic death (placebo 0.5% vs. active drug 1.6%). The incidence
      of increased ventricular premature depolarizations was equivalent (3% to 5%) for
      the three study drugs and indistinguishable from that seen with placebo. Patients
      with increased ventricular premature depolarizations on the first drug tested had
      fewer at baseline (65 +/- 94 vs. 137 +/- 260 per hour; mean +/- SD) (p < 0.01).
      When increased ventricular premature depolarizations occurred with the first
      drug, they were much more likely also to be present with the second drug (for
      example, 42% vs. 5%, p < 0.001). Increased ventricular premature depolarizations
      during initiation of therapy independently predicted increased risk of subsequent
      arrhythmic death (independent relative risk 2.34, p = 0.0053) in the absence of
      continued antiarrhythmic drug therapy. CONCLUSIONS: The overall incidence of
      early worsening of arrhythmia in the present study was low. In the absence of
      placebo control, the incidence of proarrhythmia will be overestimated. Increased
      ventricular premature depolarizations had characteristics that suggest they often
      represent spontaneous variability rather than proarrhythmia. The main finding is
      that markedly increased ventricular premature depolarizations during drug
      titration predict long-term increased risk of arrhythmic death in this patient
      population despite absence of long-term antiarrhythmic drug therapy.

PMID- 8144780
TI  - Double sequential external shocks for refractory ventricular fibrillation.
AB  - OBJECTIVES: A technique for terminating refractory ventricular fibrillation is
      described. BACKGROUND: Refractory ventricular fibrillation can occur in up to
      0.1% of electrophysiologic studies. Animal studies have shown that rapid
      sequential shocks may reduce ventricular fibrillation threshold. METHODS: Five
      patients of 2,990 consecutive patients in a 3-year period experienced refractory
      ventricular fibrillation during 5,450 routine electrophysiologic studies.
      Multiple shocks were delivered by means of a single defibrillator. Double
      sequential shocks were delivered externally 0.5 to 4.5 s apart by means of two
      defibrillators with separate pairs of electrodes. RESULTS: In all patients,
      standard defibrillation was unsuccessful, but all were successfully resuscitated
      using the double sequential shocks. CONCLUSIONS: This report stresses the
      importance of an additional defibrillator being readily available during
      electrophysiologic testing. This technique of rapid, double sequential external
      shocks may have general applicability, providing a simple and potentially
      lifesaving approach to refractory ventricular fibrillation.

PMID- 8144781
TI  - Late ventricular arrhythmia is rare after early repair of tetralogy of Fallot.
AB  - OBJECTIVES: This study was conducted to describe the incidence of ventricular
      arrhythmia during prospective long-term follow-up in a group of patients who had
      repair of tetralogy of Fallot during early childhood. BACKGROUND: Ventricular
      arrhythmia has been a common finding in patients who have undergone repair of
      tetralogy of Fallot in late childhood or as adults. Whether earlier repair lowers
      the incidence of late ventricular arrhythmia or late sudden death is unknown.
      METHODS: Twenty-nine asymptomatic patients who underwent repair at age 1.2 to 7.7
      years (mean [+/- SD] age 4 +/- 1.4 years) between 1979 and 1984 were studied.
      Twenty-one patients had simple repair (Group A), and eight had complex or
      multiple operations (Group B). All had ambulatory electrocardiographic monitoring
      preoperatively, postoperatively, at early follow-up (after 4.2 +/- 1.3 years) and
      again at late follow-up (after 11.8 +/- 1.3 years). At late follow-up, 28
      subjects also underwent echocardiography, and 26 had an exercise test. RESULTS:
      No patient had significant ventricular arrhythmia (> or = modified Lown grade 2)
      before or immediately after repair. There was no significant increase in the
      incidence of arrhythmia at early and late follow-up (14% to 28%), but at each of
      these periods the incidence of ventricular arrhythmia was higher in Group B
      patients (3 [43%] of 7 vs. 1 [5%] of 22 with early repair, p = 0.03; 6 [75%] of 8
      vs. 2 [10%] of 21 with late repair, p = 0.001). No patient had symptoms of
      arrhythmia, and there were no sudden deaths. Late ventricular arrhythmia did not
      correlate with estimated right ventricular systolic pressure, outflow tract
      gradient or degree of pulmonary incompetence or right ventricular dilation. On
      exercise, 5 (19%) of 26 patients had ventricular premature complexes at low
      levels of exercise that were suppressed at maximal exercise in all patients.
      CONCLUSIONS: Late ventricular arrhythmia is rare in patients with successful
      early correction of tetralogy of Fallot, unless complex or multiple operations
      are performed.

PMID- 8144782
TI  - Prognostic significance of ventricular arrhythmia after repair of tetralogy of
      Fallot: a 12-year prospective study.
AB  - OBJECTIVE: The aim of this study was to examine the prognostic significance of
      ventricular arrhythmia on the ambulatory electrocardiogram (ECG) after repair of
      tetralogy of Fallot. BACKGROUND: Ventricular arrhythmia is common after repair of
      tetralogy of Fallot and has been proposed as the basis for late sudden death. The
      prognostic significance of ventricular arrhythmia on ambulatory ECG and the
      indications for therapy are uncertain. METHODS: We performed a 48-h ambulatory
      ECG in 86 patients (3 to 45 years old [mean age 14 years]) after repair of
      tetralogy of Fallot. These patients were then followed up prospectively for 12
      years. RESULTS: At initial assessment in 1980, 47 patients (55%) had infrequent
      uniform ventricular extrasystoles (16 patients) or normal cardiac rhythm (31
      patients) Group 1), and 39 patients (45%) had frequent uniform ventricular
      extrasystoles (> 30/h, 2 patients), complex extrasystole (30 patients) or
      nonsustained ventricular tachycardia (7 patients) (Group 2). There were no
      significant clinical or hemodynamic differences between the groups. In addition,
      nine patients had supraventricular tachyarrhythmia. Antiarrhythmic therapy was
      prescribed only for the 10 patients who had symptoms attributable to arrhythmia.
      There were two sudden deaths in Group 1 (4%) and one nonsudden death in Group 2
      (2.5%). The absolute difference in mortality between groups was therefore 1.5%
      (95% confidence limits -6% to +9%), excluding a clinically significant difference
      in outcome. All but 1 of the 39 patients with complex ventricular arrhythmia are
      alive and well, including those with elevated (> or = 60 mm Hg) right ventricular
      pressure. CONCLUSIONS: Nonsustained ventricular arrhythmia on ambulatory ECG does
      not identify patients at high risk for sudden death after repair of tetralogy of
      Fallot. There does not appear to be any advantage in potentially dangerous long
      term antiarrhythmic therapy for asymptomatic postoperative patients.

PMID- 8144783
TI  - Acute rejection after heart transplantation: noninvasive echocardiographic
      evaluation.
AB  - OBJECTIVES: The purpose of this study was to assess the reliability of
      echocardiography in the noninvasive diagnosis of acute rejection in heart
      transplant recipients. BACKGROUND: Although echocardiographic results seem to
      correlate well with allograft rejection, published data are limited and
      contradictory. METHODS: In 130 transplant recipients, 1,400 serial
      echocardiograms were recorded within 24 h of endomyocardial biopsy. Increased
      wall thickness, myocardial echogenicity, pericardial effusion, shorter pressure
      half-time, isovolumetric relaxation time and a decrease in left ventricular
      ejection fraction were considered markers of rejection. RESULTS: The distribution
      of echocardiographic markers revealed highly significant differences between
      bioptically graded moderate, mild and no rejection and between untreated and
      treated rejection episodes (both chi-square test, p < 0.0001). Specificity was
      98.6% for two markers, but sensitivity was good (80%) for only moderate rejection
      because of the large number of false negatives in untreated patients with mild
      rejection. In untreated patients, there was a highly significant difference in
      the number of echocardiographic criteria between a benign and nonbenign outcome
      (chi-square test, p < 0.0001). In treated patients, the significant difference in
      the variation in echocardiographic criteria between favorable and unfavorable
      responses after 1 week was more pronounced after 2 weeks (t test, p < 0.01 vs. <
      0.001). Diastolic indexes and pericardial effusion at 2 weeks seemed to be
      predictive of therapeutic response. CONCLUSIONS: Poor sensitivity to mild
      rejection indicates that serial echocardiography cannot supplant endomyocardial
      biopsy in the early diagnosis of acute rejection, but it seems to be a reliable
      noninvasive means of identifying acute rejection requiring intensified
      immunosuppressive therapy and of evaluating outcome.

PMID- 8144784
TI  - Accumulation of T lymphocytes and expression of interleukin-2 receptors in
      nonrheumatic stenotic aortic valves.
AB  - OBJECTIVES: Cell-specific antibodies were used to identify immunocompetent cells
      in a comparison of valves from patients who had symptomatic tricuspid aortic
      stenosis with subjects who had no evidence of valvular heart disease. BACKGROUND:
      Nonrheumatic valvular aortic stenosis is the most common valvular heart disease
      among adults. The biologic processes involved in the development of this disease
      are poorly understood. METHODS: Tricuspid stenotic aortic valves were obtained
      from 19 patients undergoing surgery for nonrheumatic valvular aortic stenosis,
      and 10 control valves were collected at autopsy. The valves were fixed in
      formaldehyde, cryosectioned and stained with antibodies against fibroblasts,
      endothelial cells, macrophages, T lymphocytes and interleukin-2 receptors. A
      subset of valves were also analyzed with antibodies against T-helper cells and
      cytotoxic T cells. RESULTS: Stenotic valves were characterized by a basal
      accumulation of calcium deposits and a cell-rich subendothelial thickening. The
      immunohistologic analysis indicated that the cells in the subendothelial
      connective tissue were fibroblasts. T lymphocytes appeared to be the most common
      cell type in the vicinity of the calcium deposits and were also found close to
      the endothelial lining of the valves. T-helper cells were more frequent than
      cytotoxic T cells. Expression of interleukin-2 receptors occurred at the same
      location as T lymphocytes. Control valves lacked subendothelial thickening and
      contained only few cells reacting with antibodies against lymphocytes and
      macrophages. CONCLUSIONS: The presence of activated T lymphocytes in tricuspid
      stenotic valves suggests that immunologic mechanisms may be involved in the
      etiology of nonrheumatic aortic stenosis.

PMID- 8144785
TI  - Immunoscintigraphy using technetium-99m-labeled anti-NCA-95 antigranulocyte
      antibodies as an adjunct to echocardiography in subacute infective endocarditis.
AB  - OBJECTIVES: This study was performed to assess the clinical value of
      immunoscintigraphy in subacute infective endocarditis. BACKGROUND: Radiolabeled
      granulocytes can reveal inflammatory lesions. METHODS: Using technetium-99m
      labeled anti-NCA-95 anti-granulocyte antibodies, planar scintigraphy and single
      photon emission computed tomography of the thorax were performed in 72
      consecutive patients with suspected endocarditis. Each patient also underwent
      transthoracic and, if findings were negative, transesophageal echocardiography.
      RESULTS: Thirty-three patients were found to have endocarditis on the basis of
      clinical criteria (surgical confirmation in 17 patients), and the remaining 39
      served as control subjects. Initial scintigraphy was true positive in 26 patients
      (sensitivity 79%) and false positive in 7 (specificity 82%). Echocardiography was
      true positive in 29 patients (sensitivity 88%) and false positive in 1
      (specificity 97%). Scintigraphy was positive in the four patients with false
      negative echocardiography, and echocardiography was positive in the seven
      patients with false negative scintigraphy. Thus, the combination of scintigraphy
      and echocardiography yielded a sensitivity of 100% and a specificity of 82%. In
      10 of the 11 patients with two to three follow-up studies, scintigraphy became
      negative parallel to clinical improvement, indicating decreasing floridity of the
      inflammatory process. CONCLUSIONS: Immunoscintigraphy in patients with subacute
      infective endocarditis provides valuable diagnostic information in equivocal
      echocardiographic findings and may be used to monitor antibiotic therapy.

PMID- 8144786
TI  - Filling patterns in left ventricular hypertrophy: a combined acoustic
      quantification and Doppler study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the potential of acoustic
      quantification compared with Doppler echocardiography for assessment of left
      ventricular diastolic dysfunction. BACKGROUND: Diastolic dysfunction usually
      accompanies left ventricular hypertrophy. Although Doppler echocardiography is
      widely used, it has known limitations in the diagnosis of diastolic
      abnormalities. The ventricular area-change waveform obtained with acoustic
      quantification technology may provide an alternative to assess diastolic
      dysfunction. METHODS: Potential acoustic quantification variables (peak rate of
      area change and mean slope of area change rate during rapid filling, amount of
      relative area change during rapid filling and atrial contraction) were obtained
      and compared with widely used Doppler indexes of ventricular filling
      (isovolumetric relaxation time, pressure half-time, peak early diastolic
      velocity/peak late diastolic velocity ratio, rapid filling, atrial contribution
      to filling) in 16 healthy volunteers and 30 patients with left ventricular
      hypertrophy. RESULTS: Criteria for abnormal relaxation were present in 68% of
      patients by acoustic quantification and in 64% of patients by Doppler
      echocardiography. However, abnormal relaxation was identified in 80% of patients
      by one or both methods. Acoustic quantification indicated abnormal relaxation in
      the presence of completely normalized Doppler patterns and in patients with
      mitral regurgitation or abnormal rhythm with unreliable Doppler patterns.
      CONCLUSIONS: Acoustic quantification potentially presents a new way to assess
      diastolic dysfunction. This technique may be regarded as complementary to Doppler
      echocardiography. The combined use of the methods may improve the diagnosis of
      left ventricular relaxation abnormalities.

PMID- 8144787
TI  - Quantitation of absolute regional myocardial perfusion using cine computed
      tomography.
AB  - OBJECTIVES: The purpose of this study was to develop and test a method for
      quantitation of regional myocardial perfusion using cine computed tomography.
      BACKGROUND: Cine computed tomography is a relatively new cardiac imaging
      technique with excellent temporal and spatial resolution. Application of this
      technique to the study of human coronary circulation could substantially broaden
      our knowledge of human cardiac pathophysiology. This goal has been previously
      approached with some success. However, no method to date has shown validated
      accuracy of regional perfusion measurements over the entire range of
      physiologically important flow states. METHODS: Eight anesthetized dogs underwent
      thoracotomy for instrumentation. They were then studied during baseline flow
      conditions, after coronary vasodilation with intravenous dipyridamole and after
      coronary stenosis or occlusion. Regional myocardial perfusion was assessed by
      cine computed tomography using a method that includes estimates for myocardial
      blood volume and rate of myocardial enhancement after an aortic root contrast
      medium infusion. Measurements made nearly simultaneously by the radioactive
      microsphere method served as a reference standard. RESULTS: A total of 32
      perfusion conditions were studied with a range of 4 to 593 ml/min per 100 g.
      There was reasonable agreement between the two methods of measurement throughout
      the whole range of perfusion states: r = 0.97, regression slope 0.99, intercept 2
      ml/min per 100 g. In zones not subserved by a stenosed or occluded artery, cine
      computed tomography accurately depicted perfusion homogeneity with a coefficient
      of variation of 13 +/- 1% (mean +/- SE) versus 11 +/- 1% for the microsphere
      method (p = NS). CONCLUSIONS: Cine computed tomography is capable of providing
      accurate, quantitative assessment of regional myocardial perfusion over a broad
      range of perfusion states. This method, if extended to the study of humans, could
      enhance the understanding of disorders of the coronary circulation in human
      cardiovascular disease states.

PMID- 8144788
TI  - Ebstein's anomaly: outcome of pregnancy.
AB  - OBJECTIVES: The outcome of pregnancy in Ebstein's anomaly was studied in 72 such
      patients (44 women, 28 men) who had had pregnancies or fathered children.
      BACKGROUND: Patients with Ebstein's anomaly often reach childbearing age. Reports
      of the outcome of pregnancy in Ebstein's anomaly are available; however, the
      number of patients is small. METHODS: The medical and surgical data bases at the
      Mayo Clinic were reviewed, and 145 patients (62 men, 83 women) of childbearing
      age with Ebstein's anomaly were located. All patients were contacted, and 72
      patients (44 women, 28 men) with offspring were identified and reviewed in detail
      to assess the outcome of pregnancy. RESULTS: Forty-four women had 111 pregnancies
      resulting in 85 live births (76%). Seventy-six deliveries (89%) were vaginal, and
      nine (11%) were by cesarean section. Twenty-three deliveries were premature.
      There were 19 spontaneously unsuccessful pregnancies, 7 therapeutic abortions and
      2 early neonatal deaths. The mean birth weight of the infants born to cyanotic
      women was 2.53 kg, which was significantly lower than the mean birth weight of
      infants born to acyanotic women (3.14 kg [p < 0.001]). The overall incidence of
      congenital heart disease in the 158 offspring of parents with Ebstein's anomaly
      was 4% (6 of 158). The incidence of congenital heart disease was 6% (5 of 83) in
      the offspring of women with Ebstein's anomaly and 1% (1 of 75) in that of men.
      There was a 0.6% (1 of 158) incidence of familial Ebstein's anomaly. There were
      no serious pregnancy-related maternal complications, which included maternal
      death, stroke, congestive heart failure, arrhythmias or endocarditis.
      CONCLUSIONS: Pregnancy in women with Ebstein's anomaly is well tolerated. It is
      associated with an increased risk of prematurity, fetal loss and congenital heart
      disease in the offspring. In addition, a significantly lower birth weight is
      found in the offspring of cyanotic versus acyanotic women with Ebstein's anomaly.
      Paternal Ebstein's anomaly also seems to result in an increased risk of
      congenital heart disease in the offspring compared with the incidence in the
      general population.

PMID- 8144789
TI  - Implications of mitral valve prolapse in children with rheumatic mitral
      regurgitation.
AB  - OBJECTIVES: This study was conducted to determine the longterm prognosis of
      children with mitral valve prolapse associated with isolated rheumatic mitral
      regurgitation. BACKGROUND: Rheumatic fever may result in mitral valve prolapse,
      which sometimes leads to severe mitral regurgitation requiring surgical
      intervention during the active stage of rheumatic fever. However, the influence
      of mitral valve prolapse on the prognosis of patients with rheumatic mitral
      regurgitation remains largely unknown. METHODS: From 1971 to 1991, 181 children
      who fulfilled the revised Jones criteria of rheumatic fever were identified from
      a rheumatic fever prevention program. Of the 181 patients, isolated mitral
      regurgitation was diagnosed in 123 at age 4 to 12 years. The diagnosis of mitral
      valve prolapse was based on echocardiographic findings. Actuarial event-free
      curves for persistent murmur, cardiac improvement and surgical intervention were
      drawn according to the Kaplan-Meier nonparametric estimation. RESULTS: Evidence
      of mitral valve prolapse was shown in 37 (30%) of the 123 patients. Patients with
      mitral valve prolapse were more likely to have a larger cardiac size than those
      without mitral valve prolapse during the active stage of rheumatic fever.
      Although the cardiac status of patients with mitral valve prolapse may improve
      under adequate secondary prophylaxis, an actuarial analysis indicated that
      patients with mitral valve prolapse had a greater likelihood of murmur
      persistence and surgical intervention. This trend toward murmur persistence was
      observed even when patients with heart failure during the active stage of
      rheumatic fever were excluded from analysis. CONCLUSIONS: The presence of mitral
      valve prolapse in children with isolated rheumatic mitral regurgitation may
      predict a less favorable outcome.

PMID- 8144790
TI  - The neonatal heart has a relatively high content of total collagen and type I
      collagen, a condition that may explain the less compliant state.
AB  - OBJECTIVES: This study evaluated the extent of the collagen network in neonatal
      heart muscle and whether the type I/type III collagen ratio is the same as in the
      adult heart. BACKGROUND: The functional integrity and the stress-strain relation
      of heart muscle depends largely on the extracellular collagen matrix. The
      question therefore arises whether the altered compliance of the neonatal heart
      could relate to the developmental state of collagen and, in particular, the
      distribution of types I and III collagen. Type I collagen mainly provides
      rigidity and type III collagen elasticity. METHODS: Specimens from the left
      lateral wall of the left ventricle of human hearts (immature to full term, n =
      23; 3 weeks to 12 years, n = 17) were used to determine the total collagen
      amount, using the hydroxyproline assay. Similar left ventricular specimens of
      human hearts (fetal to mature, n = 20; 2 months to 1.5 years, n = 6) were fixed
      in formalin, paraffin embedded and stained with Sirius red F3BA for total
      collagen. The ratio of total collagen to total protein was quantified
      spectrophotometrically. Frozen sections of left ventricular myocardium (immature
      to mature, n = 17; 4 months to 12 years, n = 10) were stained with antibodies
      raised against types I and III collagen. Antibody titration was done on human
      leiomyoma tissue with a known type I/type III collagen ratio. The endomysial
      collagen types were quantified using a spectrophotometer and expressed as a
      ratio. Adult human myocardium (n = 10) was used as reference. RESULTS: The study
      showed that the total amount of collagen increases with age. However, the ratio
      of total collagen to total protein and the ratio of type I to type III collagen
      were very high in hearts of the very young. During development, a gradual
      decrease occurred, with the total collagen/total protein ratio reaching normal
      levels at approximately 5 months after birth and the type I/type III collagen
      ratio stabilizing at a much later age. CONCLUSIONS: These findings suggest that
      the relative high content of collagen, related to the myocytes, and the high
      ratio of type I to type III collagen provide the substrate for a rigid, less
      compliant heart in neonates.

PMID- 8144791
TI  - Management of atrial flutter after the Fontan procedure.
AB  - OBJECTIVES: The purpose of this study was to review the management of atrial
      flutter occurring after the Fontan procedure. BACKGROUND: Atrial flutter occurs
      frequently after the Fontan procedure and is often hemodynamically poorly
      tolerated. METHODS: The patients' charts were reviewed for relevant information.
      RESULTS: Between 1984 and 1992, 18 patients had atrial flutter after the Fontan
      procedure. The underlying heart defect was tricuspid atresia in nine, mitral
      atresia in six and double inlet left ventricle in three. All but three patients
      had undergone previous palliative surgery. The time interval from Fontan
      operation to atrial flutter was < 1 day to 16 years (mean 3.7 years). Seven had
      early atrial flutter before leaving the hospital. Electrophysiologic study in 15
      showed sinus node dysfunction in 12. Atrial flutter was inducible in all
      patients, and 13 had > 1 flutter configuration. Digoxin and a variety of other
      antiarrhythmic agents (mean 2.7 drugs/patient) were tried with poor results. Only
      digoxin, amiodarone, flecainide and propafenone showed some benefit when used
      alone or in combination. Antitachycardia pacemakers were implanted in 16 patients
      (endocardial 14, epicardial 2) and, with drugs, were useful in 8 (50%). Because
      atrial flutter was resistant to treatment, right atriectomy was performed in
      three patients (with benefit in two, one death), successful radiofrequency
      catheter His bundle ablation in one patient and catheter ablation of atrial
      flutter in three patients (two failed, one partial success). One patient
      underwent heart transplantation, and two died suddenly. Another died of
      complications after an elective epicardial pacemaker replacement procedure.
      CONCLUSIONS: Atrial flutter after the Fontan procedure is difficult to control.
      Aggressive drug and antitachycardia pacemaker therapy help about half of the
      patients. When these measures fail, other options, such as atriectomy, His bundle
      ablation or catheter ablation of atrial flutter, need consideration. The risk of
      sudden death justifies the use of such aggressive treatment methods.

PMID- 8144792
TI  - Hemodynamic vascular forces contribute to impaired endothelium-dependent
      vasodilation in reperfused canine epicardial coronary arteries.
AB  - OBJECTIVES: We studied canine coronary arterial vasoreactivity after occlusion
      and reperfusion to examine whether reduced flow or pressure contributed to the
      abnormalities observed. BACKGROUND: Ischemia and reperfusion alter endothelial
      and myocardial function. Causative factors may include altered flow, complement
      activation or free radical production by endothelial or white blood cells after
      reoxygenation and neutrophil activation. METHODS: The coronary arteries of
      anesthetized, open chest dogs were subjected to 90-min occlusion +/- 2 h of
      reperfusion. The effect of reperfusion on arterial responses to intracoronary
      acetylcholine, nitroprusside and phenylephrine was studied using in vivo
      ultrasound. Arterial segments were also harvested, perfused ex vivo with cell
      free buffer and exposed to potassium chloride, nitroprusside, acetylcholine and
      bradykinin. The effect of ex vivo flow cessation with or without maintained
      intralumen pressure was also studied. RESULTS: Results are expressed as mean
      value +/- SEM. In vivo arterial cross-sectional area increased during infusion
      with acetylcholine (10(-5) mol/liter [18.5 +/- 9%]) and nitroprusside (10(-5)
      mol/liter [22.5 +/- 10%]) and decreased with phenylephrine (10(-5) mol/liter [7.6
      +/- 7%]). After reperfusion, acetylcholine caused 13.5 +/- 9% vasoconstriction.
      Nitroprusside and phenylephrine responses were unchanged. Reperfused arterial
      segments also showed impaired vasodilation in response to 10(-6) mol/liter of
      acetylcholine (10.6 +/- 5.1% vs. 47.1 +/- 4.9% in control vessels) and 10(-8)
      mol/liter of bradykinin (4.4 +/- 6.7% vs. 27.9 +/- 8% in control vessels). Ex
      vivo flow cessation impaired acetylcholine-mediated vasodilation, but this
      abnormality was prevented when high intralumen pressure was maintained during the
      no-flow period. CONCLUSIONS: Reduction in flow and intralumen pressure contribute
      to the impaired acetylcholine-mediated vasodilation seen after coronary
      occlusion. This is prevented by maintaining high intralumen pressure during the
      no-flow period, suggesting that hemodynamic forces may change endothelial
      function independent of circulating complement or blood cell elements.

PMID- 8144793
TI  - Positive inotropic effects of the beta 2-adrenoceptor agonist terbutaline in the
      human heart: effects of long-term beta 1-adrenoceptor antagonist treatment.
AB  - OBJECTIVES: This study was conducted to determine whether activation of cardiac
      beta 2-adrenoceptors increases contractility in humans and whether this is
      affected by long-term beta 1-adrenoceptor antagonist treatment. BACKGROUND:
      Coexistence of beta 1- and beta 2-adrenoceptors in the human heart is generally
      accepted. The functional importance of cardiac beta 2-adrenoceptors for increases
      in contractility in humans, however, has not been completely established.
      METHODS: We studied 1) the beta-adrenoceptor subtype mediating positive inotropic
      effects of the beta 2-adrenoceptor agonist terbutaline in vitro (on right atrial
      and left ventricular preparations from nonfailing human hearts) and increases in
      contractility (by measurement of systolic time intervals) in vivo in seven
      healthy male volunteers; and 2) in vivo whether long-term treatment of volunteers
      with the beta 1-adrenoceptor antagonist bisoprolol affects terbutaline-induced
      increases in contractility. RESULTS: In vitro terbutaline caused a concentration
      dependent increase in atrial and ventricular adenylate cyclase activity and force
      of contraction. Terbutaline effects were antagonized only by the beta 2
      adrenoceptor antagonist ICI 118,551, indicating that they were mediated by beta 2
      adrenoceptor stimulation. In vivo intravenous infusions of terbutaline (dose
      range 25 to 300 ng/kg body weight per min for 15 min) dose dependently increased
      heart rate and shortened the pre-ejection period and heart rate-corrected
      electromechanical systole (QS2) time. These effects are mediated predominantly by
      beta 2-adrenoceptor stimulation because they were only marginally affected by the
      beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg orally), either given 2 h
      before infusion or long term for 3 weeks. CONCLUSIONS: Stimulation of cardiac
      beta 2-adrenoceptors in humans causes not only in vitro but also in vivo positive
      inotropic effects. Long-term beta 1-adrenoceptor antagonist treatment does not
      considerably affect beta 2-adrenoceptor-mediated in vivo increases in
      contractility. Thus, it may be possible to treat patients with chronic heart
      failure and long-term beta 1-adrenoceptor antagonist therapy with beta 2
      adrenoceptor agonists if immediate inotropic support is needed.

PMID- 8144794
TI  - Prospects for site-specific delivery of pharmacologic and molecular therapies.
AB  - The local delivery of therapeutic agents to the arterial wall represents a new
      strategy for the treatment of vascular diseases, including restenosis. Approaches
      for local, intravascular, site-specific delivery include 1) direct deposition of
      therapeutic agents into the vessel wall through an intravascular delivery system;
      2) systemic administration of inactive agents followed by local activation; and
      3) systemic administration of fusion toxins that have a specific affinity to
      proliferating smooth muscle cells at the angioplasty site. In addition to
      conventional drugs, new therapeutic agents based on molecular mechanisms,
      including recombinant genes and antisense oligonucleotides, are now under
      investigation. Although development of intravascular drug delivery devices,
      including those tailored to accommodate novel therapeutic agents, offers new
      treatment options for restenosis and other vascular diseases, certain issues that
      currently limit the safety and efficacy of these approaches remain to be
      addressed.

PMID- 8144795
TI  - Managed care involvement by cardiovascular specialists: prevalence, attitudes and
      influence on practice.
AB  - OBJECTIVES: The purpose of this study was to determine the involvement in and
      attitudes toward managed care by cardiovascular specialists and the influence of
      such programs on their practices. BACKGROUND: No in-depth study has measured the
      impact of managed care on cardiovascular specialists. Therefore, we conducted a
      mail survey to determine the prevalence of managed care arrangements among
      cardiovascular specialists and variations among pediatric and adult cardiologists
      and cardiovascular surgeons; the types of managed care arrangements in which
      cardiovascular specialists are engaged; the reasons why those not participating
      in managed care have chosen not to do so; and the general attitudes among
      cardiovascular specialists with regard to various aspects of managed care. In
      addition, we evaluated the impact of managed care among several aspects of
      cardiovascular practice. METHODS: A questionnaire was mailed in the spring of
      1993 to 4,577 practicing, domestic, American College of Cardiology (ACC) members
      selected at random from within each primary cardiovascular specialty group (adult
      cardiologists, pediatric cardiologists and cardiovascular surgeons). Additional
      data concerning practice characteristics were cross tabulated using results from
      the 1992 ACC membership profile survey. RESULTS: In total, 1,961 of the 4,577
      members responded to the survey, representing a 43% response rate. Of all survey
      respondents, 76% reported entering into at least one relationship with a health
      maintenance organization (HMO) or preferred provider organization (PPO). Of those
      not participating in managed care arrangements, the most frequently mentioned
      reason was "concern over the quality of care." This reason was cited by 51% of
      those not entering into HMO relationships and 41% of those not participating in
      PPOs. The majority of respondents indicated that they do not strongly object to
      the gatekeeper approach to managing nonemergent patients, although more than half
      indicated concern that gatekeepers may not be appropriate in the management of
      cardiac emergencies. In addition, cardiovascular specialists report that under
      managed care, referrals have not increased, income has decreased, and managed
      care formularies have not substantially affected their ability to prescribe
      appropriate medication to their patients. CONCLUSIONS: Despite concerns over the
      quality of care and contract requirements and general philosophical opposition of
      cardiovascular specialists, most are becoming integrated into managed care
      environments.

PMID- 8144796
TI  - Clinical competence in insertion of a temporary transvenous ventricular
      pacemaker. ACP/ACC/AHA Task Force on Clinical Privileges in Cardiology.

PMID- 8144797
TI  - Clinical competence in invasive cardiac electrophysiological studies ACP/ACC/AHA
      Task Force on Clinical Privileges in Cardiology.

PMID- 8144798
TI  - Convocation address. Cardiovascular medicine.

PMID- 8144800
TI  - 'Nutrition integrity' is needed to improve school meals.

PMID- 8144801
TI  - The seven personal habits of highly effective dietitians. Improving the quality
      of your self and your career.

PMID- 8144799
TI  - A pilot trial of recombinant desulfatohirudin compared with heparin in
      conjunction with tissue-type plasminogen activator and aspirin for acute
      myocardial infarction: results of the Thrombolysis in Myocardial Infarction
      (TIMI) 5 trial.
AB  - OBJECTIVES: The purpose of this study was to assess the value of recombinant
      desulfatohirudin (hirudin) as adjunctive therapy to thrombolysis in acute
      myocardial infarction. BACKGROUND: Failure to achieve initial reperfusion and
      reocclusion of the infarct-related artery remain major limitations of
      thrombolytic therapy despite aggressive regimens of heparin and aspirin. Hirudin,
      a direct thrombin inhibitor, has been shown in experimental models to enhance
      thrombolysis and reduce reocclusion. METHODS: The Thrombolysis in Myocardial
      Infarction (TIMI) 5 trial was a randomized, dose-ranging, pilot trial of hirudin
      versus heparin, given with front-loaded tissue-type plasminogen activator and
      aspirin to 246 patients with acute myocardial infarction. Patients received
      either intravenous heparin or hirudin at one of four ascending doses for 5 days.
      Patients underwent coronary angiography at 90 min and at 18 to 36 h, unless
      rescue angioplasty was performed. RESULTS: The primary end point, TIMI grade 3
      flow in the infarct-related artery at 90 min and 18 to 36 h without death or
      reinfarction before the 18- to 36-h catheterization was achieved in 97 (61.8%) of
      157 evaluable hirudin-treated patients compared with 39 (49.4%) of 79 evaluable
      heparin-treated patients (p = 0.07). All four doses of hirudin led to similar
      findings in the angiographic and clinical end points. At 90 min, TIMI grade 3
      flow was present in 105 (64.8%) of 162 hirudin-treated patients compared with 48
      (57.1%) of 84 heparin-treated patients (p = NS). Infarct-related artery patency
      (TIMI grade 2 or 3 flow) was similar in the two groups (82.1% and 78.6%,
      respectively). At 18 to 36 h, 129 (97.8%) of 132 hirudin-treated patients had a
      patent infarct-related artery compared with 58 (89.2%) of 65 heparin-treated
      patients (p = 0.01). Reocclusion by 18 to 36 h occurred in 2 (1.6%) of 123
      hirudin-treated patients versus 4 (6.7%) of 60 heparin-treated patients (p =
      0.07). Death or reinfarction occurred during the hospital period in 11 (6.8%) of
      162 hirudin-treated patients compared with 14 (16.7%) of 84 heparin-treated
      patients (p = 0.02). Major spontaneous hemorrhage occurred in 1.2% of hirudin
      treated patients versus 4.7% of heparin-treated patients (p = 0.09), and major
      hemorrhage at an instrumented site occurred in 16.3% and 18.6%, respectively (p =
      NS). CONCLUSIONS: Hirudin is a promising agent compared with heparin as
      adjunctive therapy with thrombolysis for acute myocardial infarction, and its
      evaluation in larger trials is warranted.

PMID- 8144802
TI  - What every RD should know about ATP II.

PMID- 8144803
TI  - Effective leadership begins with seven habits: an interview with Stephen R.
      Covey. Interview by Nancy I. Hahn.

PMID- 8144804
TI  - Attitudes and opinions of dietetics professionals toward cost-benefit and cost
      effectiveness analyses.
AB  - OBJECTIVE: To compare the attitudes and opinions of dietitians and dietary
      managers in regard to cost-benefit analysis (CBA) and cost-effectiveness analysis
      (CEA). DESIGN: A questionnaire was sent nationwide to a sample of 1,074
      dietitians and 454 dietary managers. SUBJECTS/SAMPLES: The dietitians were
      randomly selected from three dietetic practice groups of The American Dietetic
      Association that have practitioners with administrative responsibilities in
      health care: Clinical Nutrition Management, Consultant Dietitians in Health Care
      Facilities, and Management in Healthcare Systems. The random sample of dietary
      managers was drawn from the membership list of the Dietary Managers Association.
      MAIN OUTCOME MEASURES: We hypothesized that there would be a difference between
      the dietitians and dietary managers in their attitudes about, and experiences in
      conducting CBA and CEA. STATISTICAL ANALYSES: Data analysis incorporated
      frequencies, means, and standard deviations to describe the respondents.
      Pearson's pairwise correlations and analysis of variance examined the
      significance of the relationships among the variables of the study. Scheffe's
      test was conducted to identify which variables related closely to each other.
      RESULTS: Seven hundred twenty-two usable questionnaires were returned, which gave
      an overall response rate of 47%. Although both professional groups had experience
      with reducing costs at their jobs, they did not think it important to conduct CBA
      and CEA. Neither group could distinguish between CBA and CEA. Dietitians, who
      were more positive toward using CBA and CEA, saw them as important techniques
      that could justify the value of dietetics services. Dietitians were also more
      likely than the dietary managers to use the techniques in the future. Dietitians
      were beginning to explore the techniques, but they did not feel that good sources
      of information were available for conducting CBA and CEA studies.
      APPLICATIONS/CONCLUSIONS: Our findings suggest a strong need to educate
      dietitians and dietary managers in the techniques and proper use of CBA and CEA
      in practice settings. Dietitians need to be guided to appropriate teaching
      materials and educational programs, and dietary managers first have to be
      educated about the importance and the benefits of using the techniques.

PMID- 8144805
TI  - Strategies for increasing third-party reimbursement for nutrition counseling.
AB  - OBJECTIVE AND SETTING: The purpose of this two-phase project was to determine
      whether specific interventions would affect third-party reimbursement for
      outpatient nutrition services at the Nutrition Clinic of the Los Robles Regional
      Medical Center. DESIGN, SUBJECTS, AND INTERVENTION: In phase 1, the baseline
      reimbursement rate was determined by a questionnaire mailed to 191 clients seen
      in the clinic from January 1 to September 30, 1989. The survey was completed by
      115 clients (60%). In phase 2, two strategies were used to increase
      reimbursement: instructing clients about how to file claims and providing clients
      with form letters of medical necessity to submit with their claims. The
      strategies were applied to 76 new clients from March 15 to July 31, 1991. Five
      weeks later, 67 of the 76 clients (88%) were interviewed by telephone. OUTCOME
      MEASURES: The primary outcome measures were submission rates and reimbursement
      rates. RESULTS: The results showed that in phase 1 (before intervention), 75 of
      the 115 clients surveyed (65%) submitted claims to their insurance carriers, and
      12 of the 74 clients (15%) whose claims were acted on received reimbursement. In
      phase 2, 47 of the 67 clients (70%) submitted claims, and 15 of the 36 clients
      (42%) whose claims were acted on received reimbursement. Of the 20 clients who
      did not submit claims, 8 did not apply because of time constraints, and 5 did not
      apply because of low expectations of reimbursement. APPLICATIONS/CONCLUSIONS:
      Form letters of medical necessity increased the reimbursement rate, but client
      instruction did not increase the submission rate. Most of the clients who did not
      submit a claim said they did not have time to do so. Therefore, the Nutrition
      Clinic is attempting to submit insurance forms for the clients after clients have
      paid for the consultation. Other providers of outpatient nutrition counseling who
      follow this strategy may increase the reimbursement rate.

PMID- 8144806
TI  - Determining the complexity of patient satisfaction with foodservices.
AB  - OBJECTIVES: (a) To identify the psychological dimensions representing how
      patients perceive the quality of foodservice; (b) to identify which dimensions
      best explain variation in the satisfaction ratings of patients; and (c) to
      identify subgroups based on individual characteristics of patients and contextual
      factors. DESIGN: Survey questionnaire. SETTING: Patients of a specialized acute
      care urban hospital in Canada. SUBJECTS: One hundred thirty-two hospitalized
      patients (minimum stay of 5 days) who had not received nutrition counseling.
      Subjects excluded from the study were patients with notable physical, cognitive,
      or emotional limitations; patients receiving enteral or parenteral nutrition; and
      patients from long-term-care units. MAIN OUTCOME MEASURE: Overall satisfaction
      with meals and with foodservices, and satisfaction with 26 specific foodservice
      attributes. STATISTICAL ANALYSIS: Factor analysis followed by orthogonal rotation
      (varimax), stepwise multiple regression analysis, and one-way analysis of
      variance. RESULTS: Seven dimensions represented patients' perceptions of
      foodservice: food quality, service timeliness, service reliability, food
      temperature, attitude of the staff who deliver menus, attitude of the staff who
      serve meals, and customization. Food quality was the best predictor of patient
      satisfaction with meals and foodservice, followed by customization and attitude
      of the staff who deliver menus. Individual characteristics (gender, age,
      education, perception of degree of control over health, and belief that food
      influences one's health status) and contextual factors (normal or therapeutic
      diet, time spent at rest, and appetite) influenced patient satisfaction.
      IMPLICATIONS: The results emphasize the need for a comprehensive and
      differentiated approach in measuring and monitoring patient satisfaction with
      foodservices.

PMID- 8144807
TI  - Lipid levels in adults with cystic fibrosis.
AB  - OBJECTIVE: To examine the hypothesis that an energy-dense, high-fat diet, which
      is necessary to maintain weight in adults with cystic fibrosis, does not result
      in high serum cholesterol levels. DESIGN: Dietary, anthropometric, and
      biochemical data were correlated. SETTING: A cystic fibrosis center in
      Pittsburgh, Pa. SUBJECTS: Thirty-one adults with cystic fibrosis, 50 obligate
      carriers of the cystic fibrosis gene, and 26 controls who did not have cystic
      fibrosis. MAIN OUTCOME MEASURES: Adults with cystic fibrosis had a lower mean
      serum cholesterol level and higher mean intakes of energy and fat than controls.
      STATISTICAL ANALYSES PERFORMED: Student's t test was used to determine the
      statistical significance between two means. Univariate correlation coefficients
      were determined to measure the relative intensity of association between two
      variables. RESULTS: Mean total serum cholesterol levels in men with cystic
      fibrosis was 3.1 mmol/L vs 4.7 mmol/L in male controls (P < .001). Mean total
      serum cholesterol levels in women with cystic fibrosis was 3.2 mmol/L vs 4.3
      mmol/L in female controls (P < .001). Three adults with cystic fibrosis and no
      signs of pancreatic insufficiency had serum cholesterol levels in the high normal
      range. Carriers had serum lipid levels in the same range as the controls.
      CONCLUSIONS/APPLICATIONS: The findings indicate that a high-energy, high-fat diet
      does not raise serum lipid levels in those patients with cystic fibrosis and
      pancreatic insufficiency. However, those individuals with cystic fibrosis and
      normal pancreatic function may be at the same risk as the general population for
      developing high serum lipid levels. They should have their serum lipid levels
      monitored and be given appropriate dietary recommendations.

PMID- 8144808
TI  - Key modifiable factors in weight maintenance: fat intake, exercise, and weight
      cycling.
AB  - OBJECTIVE: This 6- to 42-month follow-up study of a 6-month worksite weight
      control intervention examined predictors of weight maintenance, with a focus on
      those that could be modified. SUBJECTS: Twenty-nine participants, 14 men and 15
      women, from a behavior modification program completed follow-up measurements.
      MAIN OUTCOME MEASURES: Height, weight, waist-to-hip ratio, food and beverage
      intake from a 3-day food record, weight history, social support and physical
      activity were the main outcome measures. RESULTS: One third of the participants
      maintained their weight losses within 2 kg at follow-up, although all had higher
      relative weights at follow-up than immediately after the program. High daily fat
      consumption (r = .40) and reduced time in physical activity (r = .34) correlated
      with increased relative weight at follow-up (P < .05). APPLICATION: Because
      previous weight cycling was so strongly related to weight loss maintenance (r =
      .55), potential weight program participants should learn and practice the weight
      maintenance behaviors of reduced dietary fat and regular exercise, independently
      of and before weight reduction attempts.

PMID- 8144809
TI  - Experience with enteral nutrition in a hospital population of acutely ill
      patients.
AB  - Enteral feeding has unique metabolic and immune advantages. This article
      describes the successful use of enteral nutrition, alone or in combination with
      parenteral feeding, in a tertiary-care hospital. Study participants were 89
      patients who received enteral feeding during a 6-month period. These critically
      ill patients (ranging in age from 55 to 71 years) had severity of illness levels
      of 7 to 25 according to the Acute Physiologic and Chronic Health Evaluation
      (APACHE II) system and lengths of hospital stay from 27 to 73 days. Mortality was
      as high as 50% in patients with liver disease (nonmalignant), 35% in patients
      with cardiothoracic and vascular diseases, and 17% in patients with cancer and
      other diseases. Despite the severity of illness, patients met their energy and
      protein intake goals through enteral or combined feeding with total parenteral
      nutrition. Serial weights (ie, obtained weekly) and serum albumin concentrations
      did not improve during hospitalization. Complications related to enteral feeding
      were minimal (< 17% incidence). Differences were noted between survivors and
      nonsurvivors: nonsurvivors had lower serum albumin concentrations at the time of
      admission, had longer hospitalizations, and required total parenteral nutrition
      for more days than the survivors. Nonetheless, even with extremely sick patients,
      provision of enteral nutrition can be successful using the administration
      techniques we describe. Enteral nutrition could best be provided by beginning at
      a slow rate (10 c3/hour), inserting the feeding tube past the pylorus, and
      feeding according to sensible energy goals (25 kcal/kg of body weight), and using
      elemental then polymeric formulas.

PMID- 8144810
TI  - Quality delegation grid: a decision tool for evaluating delegation of management
      tasks in hospital dietetics departments.
AB  - This research was designed to determine perceptions of the quality of task
      performance; identify personnel currently performing selected management and food
      production tasks in a hospital dietetics department; and develop a grid for
      examining delegation strategies. Information on task quality and delegation was
      obtained from 309 dietitians and 208 support personnel in 151 hospitals. This
      information was used to develop a quality delegation grid. The grid is divided
      into four quadrants: High Quality/High Delegation; High Quality/Low Delegation;
      Low Quality/High Delegation; and Low Quality/Low Delegation. The grid was used to
      evaluate the delegation of management tasks reported by participants in this
      study. Our results indicated that the majority of tasks were placed in the High
      Quality/High Delegation quadrant (28 tasks) and the Low Quality/Low Delegation
      quadrant (17 tasks), suggesting that delegation was appropriate for the quality
      expected if the task was delegated. Three tasks were placed in the Low
      Quality/High Delegation quadrant indicating that tasks were delegated even though
      quality of the completed task was perceived as low when delegated, suggesting
      that dietitians should have performed these tasks themselves. Four tasks were
      placed in the High Quality/Low Delegation quadrant indicating that dietitians
      were performing tasks that were perceived to have high quality when performed by
      support personnel, yet these tasks were rarely delegated. Foodservice directors
      could use the grid to identify training needs, differentiate perceptions between
      dietitians and support personnel, and evaluate current delegation patterns.

PMID- 8144811
TI  - Soluble fiber and serum lipids: a literature review.
AB  - Although fiber has been increasingly recognized as an important dietary
      constituent, controversy and confusion still exist about the physiologic effects
      of fiber. Specifically, the independent ability of dietary fiber to lower serum
      lipid levels is controversial. The purpose of this article is to review available
      evidence regarding the impact of soluble fibers on serum lipid levels. Soluble
      fibers appear to have a greater potential to alter serum lipid levels than do
      insoluble fibers. Significant reduction in the level of serum total cholesterol
      by soluble fiber was found in 68 of the 77 (88%) human studies reviewed. Of the
      studies measuring low-density lipoprotein cholesterol, 41 of 49 (84%) reported
      significant reductions. No significant changes were reported in 43 of the 57
      (75%) studies that reported high-density lipoprotein cholesterol and/or in 50 of
      the 58 (86%) studies that measured triglyceride levels.

PMID- 8144812
TI  - Evaluation of nutrition counseling in clinical settings: do we make a difference?

PMID- 8144813
TI  - Nutrition services in neonatal intensive care: a national survey.

PMID- 8144814
TI  - Dietary intake of adolescents with Crohn's disease.

PMID- 8144815
TI  - Providers of food to homeless and hungry people need more dairy, fruit,
      vegetable, and lean-meat items.

PMID- 8144816
TI  - Effects of nutrition education on calcium intake in the elderly.

PMID- 8144818
TI  - President's page: creating your future--career opportunities in an era of change.

PMID- 8144817
TI  - Position of the American Dietetic Association: nutrition care for pregnant
      adolescents.

PMID- 8144819
TI  - Is geriatrics a primary care or subspecialty discipline?
AB  - OBJECTIVE: To determine how much of the clinical care provided to older persons
      by geriatricians is primary versus consultative. DESIGN: National Survey.
      PARTICIPANTS: Candidates for the 1988 certifying examination in geriatrics,
      physicians who expressed interest in the examination but did not register for the
      examination, and physicians who expressed no interest in the examination
      (comparison group physicians). RESULTS: Based on a 72% response rate, 78% of the
      care rendered by certified internal medicine geriatricians and 90% of the care
      rendered by certified family practice geriatricians to older persons was primary
      care. Internal medicine geriatricians spent a greater percentage of their care of
      older persons providing primary care compared with internists with no interest in
      geriatrics. Although internist geriatricians who were formally trained or had
      additional subspecialty certification provided less of their care as primary care
      compared with geriatricians who had no formal training, the majority of care
      (approximately 70%) provided by each of these two subgroups was primary care.
      CONCLUSIONS: The vast majority of care provided to older persons by geriatricians
      is primary care, and these physicians should be considered as generalists for
      health policy and educational purposes.

PMID- 8144820
TI  - Nutrition and function: is there a relationship between body mass index and the
      functional capabilities of community-dwelling elderly?
AB  - OBJECTIVE: To determine if there is a relationship between body mass index and
      the ability to perform the usual activities of living in a sample of community
      dwelling elderly. DESIGN: Secondary data analysis of The National Health and
      Nutrition Examination Survey-I Epidemiologic Follow-up Study (1982-1984). Follow
      up home interview of a population-based sample originally interviewed between
      1971 and 1975 in the National Health and Nutrition Examination Survey-I (NHANES
      I). PARTICIPANTS: Survivors of the original NHANES-I cohort who were 65 years of
      age or older and who were living at home at the time of the second interview (n =
      3061). Excluded were those who could not be found, refused participation, or were
      institutionalized (n = 220), and those without complete height and weight data (n
      = 194). MAIN OUTCOME MEASURE: Functional status as measured by a 26-item battery.
      RESULTS: Bivariate analysis revealed a greater risk for functional impairment for
      subjects with a low body mass index or a high body mass index. The greater the
      extreme of body mass index (either higher or lower), the greater the risk for
      functional impairment. Logistic regression analysis indicated that both high and
      low body mass index continued to be significantly related to functional status
      when 22 other potential confounders were included in the model. CONCLUSION: The
      body mass index is related to the functional capabilities of community-dwelling
      elderly. The inclusion of this simple measurement in the comprehensive assessment
      of community-dwelling elderly is supported.

PMID- 8144821
TI  - The relationship between disease and function and perceived health in very frail
      elders.
AB  - OBJECTIVE: To study associations between disease and observed function and self
      perceived health in very frail elders. DESIGN AND SETTING: Cross-sectional survey
      of nine nursing homes in San Antonio, TX. PARTICIPANTS: 194 elderly long-stay
      nursing home residents dependent in at least two ADLs and without severe
      cognitive impairment. MEASURES: Burden of disease (BOD) was chart abstracted
      using a standardized protocol that assessed types and severities of 59
      categorizations of chronic and acute medical conditions. Observed function and
      self-perceived health status were assessed independently by the Katz Activities
      of Daily Living scale (ADL) and the Sickness Impact Profile (SIP), respectively.
      RESULTS: Summary BOD scores had a low, but statistically significant, univariate
      correlation with ADL scores (r = 0.21, P = 0.003) and no significant correlation
      with SIP scores (R = -0.008). Multiple linear regression analyses, including the
      24 most frequent disease categories, showed that disease explained significant
      amounts of ADL (r2 = 0.25, P = 0.001) and borderline significant amounts of SIP
      (r2 = 0.16, P = 0.11). Models including both disease and sociodemographic,
      cognitive, and affective variables showed disease added significant incremental
      explantation beyond the other factors to ADL (incremental r2 = 0.14, P = 0.04),
      but not to SIP (incremental r2 = 0.08, P > 0.10). CONCLUSIONS: Disease, observed
      function, and self-perceived health status are separate, but interrelated
      entities, with disease having a stronger relationship to observed function than
      self-perceived health. Comprehensive assessment of frail elders may need to
      include all three areas, and studies that focus on one area should take into
      account the other two as potential important covariates.

PMID- 8144822
TI  - Restraint reduction in a nursing home and its impact on employee attitudes.
AB  - OBJECTIVE: To reduce physical restraint use in a nursing home and increase
      employee support for the restraint-reduction program. DESIGN: A one-group pretest
      posttest design with repeated measures was used to determine changes in restraint
      use with participants over a 14-month interval. All individuals employed at the
      nursing home were surveyed at two time periods to determine their opinions on
      restraint use. SETTING: A 265-bed private, non-profit nursing home in Dallas,
      Texas. PARTICIPANTS: A restrained cohort of 170 residents with a mean age of 84
      years; 84% were female. A total of 182 employees participated in the first survey
      and 209 in the second. INTERVENTION: Formation of a project team that planned and
      supervised restraint removal. Inservice training on restraint use was conducted
      for all employees. MEASUREMENTS: Type and frequency of restraint use among the
      restrained cohort at four evaluation points within a 14-month interval. The
      frequency of restraint use in the nursing home population was also recorded.
      Survey measures included employee responses to a 16-item closed-end questionnaire
      before and after training. RESULTS: The mean number of restraints used with each
      resident in the restrained cohort decreased from 1.56 to 0.67. The number of
      residents on restraints in the nursing home was reduced during the course of the
      study (67.5% vs. 36.7%, P < 0.0001). Changes in employee opinions about restraint
      use were found after training. On the second survey, more than twice as many
      employees indicated that restraints should be removed from almost all residents
      who have them (15.2% vs 36.3%, P < 0.0001). CONCLUSION: A restraint-reduction
      program in a nursing home can produce positive results in terms of decreased
      restraint use and supportive employee attitudes. More practical alternatives to
      restraints need to be developed for application in the training of nursing home
      employees. Future studies on resident, employee, and family attitudes about
      restraint use are suggested.

PMID- 8144823
TI  - A longitudinal study of risk factors associated with the formation of pressure
      ulcers in nursing homes.
AB  - OBJECTIVE: To determine risk factors associated with the formation of stage II-IV
      pressure ulcers in nursing homes. DESIGN: Since the incidence rate for pressure
      ulcer formation varies among nursing homes, the homes were divided into tertiles
      based on these rates. Pooled logistic regression was used to model which factors
      are associated with the formation of pressure ulcers in both high and low
      incidence homes. SETTING: 78 National HealthCorp nursing homes. SUBJECTS: We
      studied 4232 nursing home residents free of pressure ulcers on admission to a
      nursing facility and at 3-months follow-up. All remained in the home for at least
      3 additional months to a maximum of 21 months. MEASUREMENTS: The effects of age,
      gender, race, antipsychotic drug use, urinary incontinence, fecal incontinence,
      body mass index, diabetes mellitus, disorientation, ambulation, physical
      restraints, activities of daily living of bathing, feeding, or transferring, and
      nursing home bed size on the formation of a stage II-IV pressure ulcer while the
      subject was a resident in the nursing home were studied. MAIN RESULTS:
      Significant factors associated with the formation of pressure ulcers in high
      incidence homes (21-month incidence = 19.3%) were ambulation difficulty (OR =
      3.3; CI = 2.0, 5.3), fecal incontinence (OR = 2.5; CI = 1.6, 4.0), diabetes
      mellitus (OR = 1.7; CI = 1.2, 2.5), and difficulty feeding oneself (OR = 2.2; CI
      = 1.5, 3.3). In the low incidence homes (21-month incidence = 6.5%), significant
      factors associated with pressure ulcer incidence were ambulation difficulty (OR =
      3.6; CI = 1.7, 7.4), difficulty feeding oneself (OR = 3.5; CI = 2.0, 6.3), and
      male gender (OR = 1.9; CI = 1.2, 3.6). CONCLUSIONS: Although low and high
      incidence homes share similar risk factors, such as ambulation and feeding
      activities of daily living, the main difference was that diabetes and fecal
      incontinence played a major role only in high risk homes, while male gender was
      an important discriminator only in low incidence homes. Yet, it is unclear if
      these factors explain the three-fold difference in the incidence rates for
      pressure ulcers in these facilities. Baseline or resident clinical characteristic
      differences of any one factor between the high and low incidence homes varied by
      no more than 5%. While we identified certain conditions which are associated with
      pressure ulcer formation, there may be unknown or unmeasured facility effects in
      addition to the characteristics of a given resident in a particular home.

PMID- 8144824
TI  - Seven consecutive days of exercise lowers plasma insulin responses to an oral
      glucose challenge in sedentary elderly.
AB  - OBJECTIVE: To assess the effects of 1 and 7 consecutive days of exercise on
      glucose and insulin responses to an oral glucose challenge. DESIGN: Intervention
      group assessed at baseline and after 1 and 7 days of exercise. SETTING: Academic
      medical institution. PARTICIPANTS: Nine healthy 60 to 80-year-old men and women.
      INTERVENTION: Seven days of 50 minutes of exercise at 70% VO2 max. MEASUREMENTS:
      Body weight, body composition, and glucose and insulin levels and responses to an
      oral glucose challenge at baseline and after 1 and 7 days of exercise. MAIN
      RESULTS: Fasting plasma insulin levels and plasma insulin responses to an oral
      glucose challenge were reduced by 15% and 20%, respectively, with 7 consecutive
      days of exercise that resulted in no change in body weight or body composition.
      No changes in glucose or insulin levels or responses to the oral glucose
      challenge were evident after a single day of exercise. CONCLUSION: The
      hyperinsulinemia associated with aging can be blunted significantly by repeated
      bouts of exercise in the elderly, independent of any changes in body composition.

PMID- 8144825
TI  - Arginine vasopressin and osmolality in the elderly.
AB  - OBJECTIVES: To evaluate the influence of age on plasma arginine vasopressin (AVP)
      concentrations and the relationship between plasma AVP and serum osmolality in
      younger and older subjects, and in the elderly, to assess the effect of gender on
      plasma AVP concentration and to determine the impact of prostaglandin blockade on
      renal responsiveness to AVP. DESIGN: Cross-sectional study; randomized, double
      blind, crossover, placebo-controlled study. SETTING: The Renal Laboratory, Royal
      North Shore Hospital (younger adults) and Clinical Room, St Vincents Hospital
      (elderly subjects). PARTICIPANTS: 45 younger adults (35 +/- 9 years), and 41
      elderly subjects (29 males, 12 females; 78 +/- 3 years). All subjects were
      healthy and non-institutionalized. The elderly subjects were screened to exclude
      significant pathology (clinical assessment, multiple investigations).
      INTERVENTION: Blood samples were drawn from all younger and elderly subjects. The
      elderly subjects were randomly allocated indomethacin or placebo for 1 month.
      Following a 1 to 2-week washout, the alternative was administered for a further 1
      month. MAIN OUTCOME MEASURES: Plasma AVP and serum osmolality and plasma AVP,
      serum, and urine osmolality at baseline were measured on indomethacin and
      placebo. RESULTS: In the elderly subjects, baseline plasma AVP concentration was
      significantly higher than in the younger subjects studied (4.7 +/- 0.7 vs 2.1 +/-
      0.2 pg/mL respectively; P = 0.0003). Plasma AVP was strongly correlated with
      serum osmolality in the younger subjects (r = 0.76, P = 0.0001) but not in the
      elderly cohort (r = -0.18, P = 0.26). No difference was found between the sexes
      in plasma AVP (P = 0.89), and indomethacin treatment did not alter the plasma
      AVP/urine osmolality ratio (P = 0.85) in the elderly subjects. In addition,
      changes in plasma AVP with indomethacin therapy did not correlate with changes in
      serum osmolality (r = 0.16, P = 0.09). CONCLUSIONS: Aging is accompanied by an
      increase in plasma AVP concentrations. In healthy, elderly subjects, plasma AVP
      is not dependent on serum osmolality and is not influenced by gender.
      Indomethacin has no effect on the renal responsiveness to plasma AVP.

PMID- 8144826
TI  - Comparison of static and dynamic posturography in young and older normal people.
AB  - OBJECTIVE: To measure sway velocity during static and dynamic posturography in
      "normal" older people and to determine which tests best distinguish young from
      older subjects. SUBJECTS: A sample of 30 young (18-39 years) and 82 community
      dwelling older (> 75 years) subjects who reported normal balance underwent a
      battery of balance tests. MEASUREMENTS: Velocity and frequency of sway, Tinetti
      gait and balance score, self-reported fear of falling and number of falls.
      RESULTS: Mean sway velocity and the ratio of high to low frequency sway velocity
      were significantly increased in older subjects compared with younger subjects for
      static and dynamic tests with eyes open and with eyes closed. Measures of
      anterior-posterior sway velocity during angular tilt of the platform with eyes
      closed best distinguished young from older subjects (almost three-fourths of
      older subjects had values greater than 2 standard deviations from the young
      normal mean). Older subjects who reported falls in the past year did not have a
      significantly higher sway velocity on static or dynamic tests compared with those
      who did not report falls. However, subjects who reported a fear of falling had
      significantly higher sway velocity on dynamic tests with eyes closed compared to
      those who did not report a fear of falling. CONCLUSIONS: On average, velocity of
      sway is higher in older subjects compared with younger subjects, and the
      difference between young and old is greater with dynamic posturography than with
      static posturography.

PMID- 8144827
TI  - The effects of the presence of a third person on the physician-older patient
      medical interview.
AB  - OBJECTIVE: To compare communication in triadic (three-person) and dyadic (two
      person) older patient medical interviews and to determine the influence of the
      presence of a third person on the physician-older patient relationship. DESIGN:
      Matched sample of dyadic and triadic audiotaped outpatient medical visits.
      Audiotapes were coded with the Multi-dimensional Interaction Analysis (MDIA)
      system. SETTING: Hospital-based medical primary care group practice in a major
      urban teaching institution. PARTICIPANTS: Patients 60 years and older who were
      making their first visit to study physicians. In a sample of 96 audiotaped
      initial medical visits, 15 encounters involved three persons. These 15 cases were
      matched with 15 dyadic interviews for gender and race of the patient and for
      gender and race of the physician. MAIN OUTCOME MEASURES: Content, interactional
      processes, and specific language and communication behaviors of older patients,
      physicians, and third persons in the medical encounter, as measured by the MDIA
      system. RESULTS: The specific content and the quality of interactional processes
      of physicians were not affected by the presence of a third person. However, older
      patients raised fewer topics in all content areas (medical, personal habits,
      psychosocial, and physician-patient relationship) in triads than in dyads.
      Overall, patients were less responsive (ie, the quality of their questioning,
      informing, and supportiveness was poorer) on patient-raised topics in triads than
      in dyads. Patients were rated as less assertive and expressive, and there was
      less joint decision-making and shared laughter in triads than in dyads. Patients
      were frequently excluded from conversations in visits in which a third person was
      present. CONCLUSIONS: The presence of a third person in the medical encounter
      changes the interactional dynamics of older patient medical interviews and may
      influence the development of a trusting and effective physician-older patient
      relationship.

PMID- 8144828
TI  - A prospective study of dehydroepiandrosterone sulfate and cognitive function in
      an older population: the Rancho Bernardo Study.
AB  - OBJECTIVE: To determine whether low plasma dehydroepiandrosterone sulfate (DHEAS)
      levels predict poor cognitive function in the elderly. DESIGN: A prospective,
      population-based study with periodic clinical evaluations and 100% follow-up for
      vital status. SETTING: Rancho Bernardo, California PATIENTS: 270 men and 167
      women (80% of surviving, local, age-eligible subjects) from the Rancho Bernardo
      cohort who had plasma obtained for DHEAS assays in 1972 to 1974 and screening for
      dementia in 1988 to 1991. MEASUREMENTS: DHEAS levels were measured by
      radioimmunoassay. There were five interviewer-administered standard screening
      tests of cognitive function: Mini-Mental Status Examination, Buschke selective
      reminding test, Trails B, category fluency, and Heaton Visual Reproduction test.
      RESULTS: DHEAS levels were higher in men than women and decreased with age in
      both sexes. There were no significant differences in age-adjusted DHEAS levels in
      the percent of men or women with categorically impaired performance on any test.
      When analyzed as a continuous variable, DHEAS levels were significantly
      correlated with only one test, the Bushke, and only in women. Low baseline DHEAS
      levels were not associated with any mention of dementia on death certificates or
      with non-participation of survivors. Low levels of DHEAS predicted mortality in
      men more than in women such that men were more likely to have died before
      cognitive function testing than women. CONCLUSION: The single DHEAS-memory
      association, restricted to women, is most likely to be spurious, consequent to
      multiple comparisons. We cannot exclude a true effect of low DHEAS, restricted to
      women and reflecting their better survival than men.

PMID- 8144829
TI  - Syncope in older persons.

PMID- 8144830
TI  - Early experiences of an ethics consult team.

PMID- 8144831
TI  - The death certificate.

PMID- 8144832
TI  - The older pedestrian.

PMID- 8144833
TI  - Report on public policy: geriatrics and the GME financing debate.

PMID- 8144834
TI  - Geriatric medicine: we are what we do.

PMID- 8144835
TI  - Geriatric medicine: is it primary care?

PMID- 8144836
TI  - On a geriatrician's role and responsibilities in the United States.

PMID- 8144837
TI  - Geriatrician and gerontologic nurse practitioner collaboration: a necessity or
      nice idea?

PMID- 8144838
TI  - Medical treatment preferences in nursing home residents.

PMID- 8144839
TI  - Effect of spectacle correction on the progression of myopia in children--a
      literature review.
AB  - BACKGROUND: Methods used to attempt to control childhood myopia progression have
      included various types of spectacle correction. The most commonly studied
      technique has been the use of bifocal lenses. METHODS: The literature on the
      effects of bifocals, undercorrection, and part-time wear of spectacles on the
      rate of myopia progression in children was reviewed. RESULTS: The data available
      on undercorrection and part-time wear of spectacles is limited. There have been
      several studies on the effects of bifocals. Some studies reported no effect with
      bifocals, some studies reported reduced rates with bifocals, and some noted lower
      rates with bifocals may be associated with particular ocular or visual findings.
      CONCLUSIONS: Critical analysis of the literature suggests that when the nearpoint
      phoria is eso, greater rates of progression occur, and that some degree of myopia
      control may be established by shifting the phoria into the normal range by
      spectacle corrections such as bifocals.

PMID- 8144840
TI  - Prevalence of refractive errors on a VOSH mission to Nicaragua.
AB  - BACKGROUND: Optometric services in many parts of the world are unavailable with a
      resultant lack of information on the epidemiology of visual problems in those
      countries as well. METHODS: A retrospective analysis was conducted on the records
      of 3,281 patients seen on a VOSH mission to Nicaragua. RESULTS: The mean
      spherical correction for each eye was a low hyperopic correction. For eyes having
      an astigmatism the mean cylinder correction was -1.00 and was usually oriented
      against the rule. CONCLUSION: There was a lower incidence of myopia in this
      population than for many others that have been studied. There was also a need for
      a presbyopic correction at an earlier age than for Mid-European populations. A
      very large number of spectacles must be donated in order to get a sufficient
      supply for a successful VOSH mission.

PMID- 8144841
TI  - Results of community-based vision screenings of older adults in the Birmingham,
      Alabama metropolitan area.
AB  - BACKGROUND: Two-hundred one adults age 65 and older underwent vision screening at
      community senior centers and nutrition sites in the Birmingham, Alabama
      metropolitan area. METHODS: Using a multiple-test format recommended by the
      American Optometric Association, 89 percent of those screened failed. Reduction
      in visual acuity associated with anterior segment abnormalities was the most
      common reason for failure. Almost half (48 percent) of the overall population had
      less than 20/50 distance acuity in both eyes. Median visual acuity for the
      population was 20/50. Median visual acuity decreased with age from 20/40 at age
      65 to 20/80 for those over the age of 85, while only 8 percent were legally
      blind. RESULTS: Results show that a large percentage of older adults have reduced
      vision without being legally blind and will fail vision screening. CONCLUSIONS:
      Given the high failure rate, the value of this type of vision screening is
      questionable.

PMID- 8144842
TI  - 6 x 1 = 1: "Really cool glasses".

PMID- 8144843
TI  - Health alliances: that's where the action will be.

PMID- 8144844
TI  - Healthy People 2000--health promotion and disease prevention, a new opportunity
      for optometrists.
AB  - The Healthy People 2000 objectives represent a major opportunity for optometry to
      expand its scope of practice, enhance its quality of patient care, and become
      involved in making policies and programs that will directly affect the services
      and patient care it provides. If optometrists take advantage of this opportunity
      they will: 1. Increase the visibility of optometry and enhance our image as the
      primary eye and vision care provider. 2. Increase the number of patients seen by
      optometrists. 3. Expand the number of organizations, policy makers and third
      party providers who understand the services optometrists provide and their
      importance in achieving the Healthy People 2000 objectives. 4. Increase the
      number of referrals from nontraditional sources. 5. Enhance the overall health of
      their patients. 6. Be recognized as the leader of health promotion and disease
      prevention activities involving eye and vision care. The question is, "Will
      optometrists become involved and use this opportunity?" We must look back from
      the perspective of the year 2000 and be able to answer this question with a
      definite YES!

PMID- 8144845
TI  - What is primary eye care?

PMID- 8144846
TI  - An historic overview of the American Public Health Association and optometric
      establishment of the Vision Care Section.

PMID- 8144847
TI  - Rationing the public's health and the optometric agenda.
AB  - BACKGROUND: Universal access to health care at an affordable price is a major
      issue on the current agenda of the nation's legislative, corporate and health
      care decision makers. METHODS: The current literature and prevailing ideologies
      on health service rationing and health care reform were reviewed and evaluated in
      the context of optometric practice. RESULTS AND CONCLUSION: The socio-political
      nature of the decision making process may lead to recommendations for reforms and
      market interventions that contravene the agenda of health care providers. To
      maintain quality of care and contain costs, and as a basis for allocation,
      judgments must be made about the value of specific services. Some services may be
      rationed according to the ratio of benefit to cost and their perceived net value
      to society. If rationing prevails, optometric services will be included in the
      process of prioritization and allocation.

PMID- 8144848
TI  - Combined treatment with growth hormone and luteinizing hormone releasing hormone
      analogue (LHRHa) of pubertal children with familial short stature.
AB  - We evaluated the 12 month growth of 18 pubertal children with familial short
      stature randomly assigned to clinical follow-up (group A), GH treatment alone
      (group B) and GH+LHRH analogue (LHRHa) treatment (group C). Height velocity
      increased significantly compared to baseline in groups A and B (4.7 +/- 0.4 vs
      6.6 +/- 0.6 and 4.4 +/- 0.3 vs 8 +/- 1 respectively), but not in C (5 +/- 0.5 vs
      6.5 +/- 0.4). Moreover in group B height and height prognosis standard deviation
      score SDS) also were higher (-2.2 +/- 0.2 vs -1.7 +/- 0.2 and 1.8 +/- 0.3 vs -1
      +/- 0.2, respectively). Comparisons among the groups showed a significant
      increase in group B vs the other groups of height velocity SDS (3.9 +/- 1.3 vs
      0.4 + 1 and 0.3 +/- 0.7) and of height prognosis SDS (-1 +/- 0.2 vs -2.4 +/- 0.3
      and -2.4 +/- 0.3). In conclusion, after one-year treatment, GH seems to be more
      effective in stimulating growth than GH +/- LHRHa, even if studies of longer
      duration and/or follow-up are needed.

PMID- 8144849
TI  - Catecholamines in hypothalamus, ovaries and uteri of rats with precocious
      puberty.
AB  - The concentration of catecholamines in the hypothalamus and reproductive organs
      of rats with hypothalamic lesions placed on the day of birth was investigated. In
      an attempt to contribute to the discussion concerning the role of catecholamines
      in regulation of puberty, the aim of this study was to examine the content of
      hypothalamic, ovarian and uterine catecholamines in female rats with precocious
      vaginal opening. The animals were sacrificed on the day of precocious puberty,
      which occurred at the age of 25.71 +/- 0.98 days. The data obtained were compared
      with intact (pubertal) controls obtained on the day of vaginal opening (40.13 +/-
      1.35 days) as well as in infantile intact controls of corresponding age of the
      lesioned animals. In the ovaries of both animals (i.e. lesioned and sacrificed on
      day of vaginal opening and the infantile controls of corresponding age), small
      and medium sized follicles were present. Ruptured follicles were evident only in
      the pubertal controls. The mass of ovaries and uteri from lesioned rats was also
      significantly lower than in the pubertal controls. Concentrations of
      norepinephrine in both ovaries and uteri on the day of vaginal opening of the
      animals with posterior hypothalamic lesions and of infantile controls, was
      significantly higher than in pubertal controls on the day of vaginal opening.
      Epinephrine was significantly higher in the uterine tissues of lesioned and
      infantile controls as compared to pubertal animals. The levels of dopamine and
      norepinephrine in the hypothalamus of lesioned and pubertal controls on the day
      of vaginal opening were significantly higher than in infantile controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8144850
TI  - Estrogenic suppression by different administration schedules of goserelin depot
      for treatment of endometriosis.
AB  - Eighteen patients affected by laparoscopically confirmed endometriosis were
      randomly assigned to three different schedules of treatment with gonadotropin
      releasing hormone agonist (GnRH-a) (goserelin depot formulation 3.6 mg) every 28
      days for 6 months. Six women received the first implant in early follicular
      phase, 4 in late luteal phase and 8 in 3rd and 17th day from onset of menses.
      Pretreatment and posttreatment laparoscopic score, performed according to the
      American Fertility Society scoring system, were compared; a significant reduction
      in the extent of disease was observed in each group investigated (A and C: p <
      0.01; B: p < 0.05). In each treatment group after the second GnRH-a implant the
      mean levels of estrone-3-glucuronide (E1-3G), daily measured in early morning
      urine specimens during the control cycle and the first three months of therapy,
      were suppressed to menopausal women range. In group B during the 2nd and 3rd
      month of therapy, the urinary mean levels of E1-3G were significantly lower than
      in group A and C. In conclusion the different goserelin depot administration
      schedules gave similar laparoscopic improvement, in spite of the first GnRH-a
      administration in luteal phase allowed a more marked estrogenic suppression.

PMID- 8144851
TI  - Vasoactive intestinal peptide-induced prolactin release in hypothyroid patients.
AB  - VIP is an established prolactin-releasing factor. VIP gene expression at the
      anterior pituitary level and the central nervous system is regulated by thyroid
      hormones. On the other hand, primary hypothyroidism leads in many cases to
      amenorrhea, galactorrhea and hyperprolactinemia. In this study we assessed
      prolactin responses to VIP (75 micrograms iv infusion over 12 min) in a group of
      six hypothyroid women (mean age +/- SE, 38.8 +/- 3.3 yr; serum TSH levels, mU/L,
      116.3 +/- 23.9), before treatment and after normalization of thyroid hormone
      levels during thyroxine (T4) replacement therapy (100-150 micrograms/day over 12
      16 weeks). Furthermore, we assessed if VIP infusion had any effects on serum GH
      levels in these patients. In hypothyroid women, VIP infusion increased serum
      prolactin concentrations with peak levels being attained at 15 min (28.8 +/- 3.4
      micrograms/L). The Area Under the Curve (AUC) was 1921 +/- 103 micrograms/L/2h.
      PRL responses to VIP were unchanged after T4 therapy, both in terms of peak
      levels (28.7 +/- 2.2 micrograms/L, NS) and of AUC (2079 +/- 261 micrograms/L/2h,
      NS). Serum GH levels were unaffected by VIP administration. In conclusion our
      study shows that, in hypothyroid patients, restoration of normal thyroid hormone
      levels by thyroxine replacement therapy does not affect lactotroph responsiveness
      to VIP. Therefore, our data do not support the hypothesis that VIP might
      contribute to the hypothyroid-induced hyperprolactinemia seen in man.

PMID- 8144853
TI  - New Gaba-containing analogues of human growth hormone-releasing hormone (1-30)
      amide: I. Synthesis and in vitro biological activity.
AB  - Analogues of human growth hormone-releasing hormone (1-30)-amide have been
      developed. All analogues have been modified in position 27 with Nle and with Gaba
      in position 30. Additional D-amino-acids have been inserted in the GHRH(1-30)-NH2
      sequence: A-1741: Nle27,Gaba30-GH-RH(1-30)-NH2 A-495: D-Ala2,Nle27,Gaba30-GH-RH(1
      30)-NH2 A-515: D Ala2,Leu15,Nle27,Gaba30-GH-RH(1-30)-NH2 A-527: D-Ala2,D
      Arg11,Leu15,Nle27,Gaba30-GH-RH(1-30)-NH2. Our analogues were synthesized by solid
      phase peptide synthesis and were tested is two different in vitro systems and in
      rat pituitary cell cultures. A-495 and A-1741 were found to be the most active in
      releasing GH, however they showed different activities in the two different test
      systems. A-495 exhibited higher potency in the superfusion system (1.63 fold
      potency of the GHRH (1-29)-amide), while A-1741 evoked higher GH release from
      cultured pituitary cells (1.5-2.5 times higher than the GH-RH(1-44)-amide). The
      other analogues (A-515 and A-527) were found to be equipotent to the standard
      molecule. We can conclude that Nle27 and Gaba30 substitutions appeared to be a
      good modification in in vitro test systems, and Gaba30 substitution served as a
      good spacer during the synthesis, since it made the coupling of the C-terminal
      amino acids easier and produced quantitative coupling. In addition to the
      advantageous properties in the synthesis these modifications with or without D
      Ala at the N-terminus increased the in vitro biological activity to 1.5-2.5 fold
      of the GHRH molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144852
TI  - Metyrapone induced increase in plasma corticotropin is not associated with
      changes in peripheral venous arginine vasopressin or corticotropin releasing
      factor.
AB  - The responses of the "stress hormones" cortisol, 11-deoxycortisol, ACTH,
      vasopressin (AVP), and corticotropin releasing factor (CRF) were studied in 6
      normal males in response to acute cortisol deficiency induced by the 11-beta
      hydroxylase inhibitor, metyrapone. A 750 mg dose was administered orally at 08:00
      h on day 1 and at 4 hourly intervals over a 24-h period. A 20 mg tablet of
      hydrocortisone or placebo was then given at 08:00 h on day 2, according to a
      randomized cross-over design. Each subject was restudied after an interval of at
      least one month. Blood samples were taken for all hormones at 08:00 h on day 1
      and at 04:00 h on day 2. Thereafter ACTH and AVP were sampled at 10-min
      intervals, CRF at 20-min intervals, and cortisol and 11-deoxycortisol at hourly
      intervals until 12:00 h on day 2. Cortisol (mean +/- SE) fell from 628 +/- 218
      nmol/l at 08:00 h (day 1) to a minimum of 230 +/- 78 nmol/l at 05:00 h on day 2.
      Plasma 11-deoxycortisol rose from 14.0 +/- 0.8 nmol/l to a maximum of 622 +/- 36
      nmol/l and plasma ACTH rose from 8.71 +/- 1.64 pmol/l to a maximum of 166.2 +/-
      57.5 pmol/l. Diurnal rhythmicity of plasma ACTH was maintained. There was no
      detectable change in plasma levels of AVP or CRF from baseline (AVP 2.5 +/- 0.8
      pmol/l, CRF 3.4 +/- 0.5 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144854
TI  - New Gaba-containing analogues of human growth hormone releasing hormone (1-30)
      amide: II. Detailed in vivo biological examinations.
AB  - Analogues of human growth hormone-releasing hormone-(1-30)-amide [GH-RH(1-30)
      amide] were tested for their ability to stimulate GH release in vivo by injecting
      the peptides intravenously (iv), subcutaneously (sc), and intramuscularly (im).
      The analogues involved derivatization with Nle27 and Gaba substituents at the C
      terminus with or without D-amino acid(s) in the peptide chain. The potency of the
      analogues was compared to that of GH-RH(1-29)-amid testing their ability to
      release GH at 5, 15 and 30 min after the administration. In iv test the potency
      of the analogues was 1.2-2 times higher than that of the GH-RH(1-29)-amide, and
      no significant differences were detected between the potencies of the analogues
      with or without D-amino acid. In the sc test the analogue with D-Ala2, Nle27, and
      Gaba30 substitutions expressed 8.0-51.7 times higher potency than the GH-RH(1-29)
      amide, however, the analogue with similar modifications but with L-Ala2 showed
      the same low potency (1.2-2.1) as in the iv test. Results from the im experiments
      were similar to those of SC test. The most potent analogues were those which had
      D-Ala2, Nle27, and Gaba30 substitutions with Gly15 or Leu15. Circular dichroism
      (CD) spectra of the analogues showed that Leu in position 15 increased the
      stability of the predominant alpha-helix conformation, which improved the
      absorption of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144855
TI  - Glycosylation of human prolactin regulates hormone bioactivity and metabolic
      clearance.
AB  - To analyze the role of individual glycosylation pattern on PRL biopotency,
      monomeric prolactin (PRL), secreted by human prolactinoma cells in culture, was
      isolated by gel filtration and separated by affinity chromatography on
      Concanavalin A-Sepharose or Lentil-Agarose. These lectins allowed the isolation
      of PRL glycoforms containing either biantennary, mannose-rich or fucosylated
      complex carbohydrate structures, respectively. Endoglycosidase treatment and
      carbohydrate content of PRL was found to be consistent with N-linked
      oligosaccharides of mannose-rich structure and complex units terminated in sialic
      acid. Mannose-rich PRL and PRL with biantennary oligosaccharides promoted cell
      growth of rat lymphoma cells to a diminished extent compared to non-glycosylated
      PRL (NG-PRL), indicating that the two major types of carbohydrate structure are
      able to decrease the intrinsic bioactivity of PRL. Metabolic clearance of the
      various forms of PRL in rats was also found to be highly dependent upon hormone
      glycosylation. The various glycosylated forms (G-PRLs) proved to be totally
      eliminated from the circulation within 60 min, faster than NG-PRL 10% of which
      was still present at that time. Mannose-rich or biantennary G-PRLs were
      differently cleared in a biphasial fashion with a similar rapid phase of about 2
      min followed by distinct slow phases of 12 and 27 min, respectively. The presence
      of fucose did not alter this distribution. In contrast, NG-PRL was eliminated
      with a half-time of approximately 5 min, followed by a very slow disappearance
      over several h. It thus appeared that glycosylation increased the metabolic
      clearance rate of PRL from 0.13 +/- 0.07 ml/min for NG-PRL to 0.47 +/- 0.12
      ml/min for PRL with biantennary carbohydrate chains and 0.8 +/- 0.2 ml/min for
      the hormone with mannose-rich oligosaccharides. The distribution of PRL to target
      and elimination organs was also found to be different according to the
      carbohydrate structure present in the hormone. NG-PRL and mannose-rich G-PRL
      showed higher incorporation in liver than biantennary G-PRL which was
      preferentially eliminated by the kidney. Altogether, the current data show that
      addition of oligosaccharides to PRL as well as carbohydrate structure contribute
      to modulate both the duration of the hormone in the blood and its distribution to
      different organs. It is proposed that glycosylation may selectively down-regulate
      PRL action at individual target tissues.

PMID- 8144856
TI  - A nonsecreting pheochromocytoma presenting as an incidental adrenal mass. Report
      on a case.
AB  - A 25 year old women presented an incidental adrenal mass which was diagnosed to
      be a pheochromocytoma before surgery by means of a positive 131-I-MIBG
      scintigraphy. Urinary vanilmandelic acid resulted repeatedly normal as well as
      basal plasma norepinephrine (NE), epinephrine (E) and dopamine (DA). Urinary
      homovannilic acid resulted in the normal range. Stimulation tests with iv
      glucagone, tyramine and metoclopramide evoked normal NE and E responses while a
      slight increase in plasma DA was observed after metoclopramide. Oral clonidine
      suppressed plasma catecholamines (CA) normally. Histologic and
      immunohistochemical studies confirmed that the tumor was a pheochromocytoma
      showing positivity for tyrosine hydroxylase but not for dopamine-beta-hydroxylase
      activity. This case is the first report on a completely asymptomatic
      pheochromocytoma presenting as an incidental adrenal mass which was investigated
      with repeated biochemical tests before surgery and demonstrates that, among the
      extremely variable functional attitudes of pheochromocytomas, a defect in CA
      synthesis and secretion is also to be included.

PMID- 8144857
TI  - Treatment of amiodarone iodine-induced thyrotoxicosis with plasmapheresis and
      methimazole.
AB  - The present report illustrates the clinical and biochemical outcome in two
      amiodarone iodine-induced thyrotoxicosis (AIIT) patients submitted to
      plasmapheresis. Amiodarone was discontinued, and treatment with MMI (40 mg/day)
      was started. In addition, patients were submitted to two sessions of plasma
      exchange, with a one-day interval between the two session. In both patients serum
      total T3 (TT3) and free T3 (FT3) concentrations decreased promptly but in
      contrast to the serum TT3, FT3 levels remained steadily above the normal range. A
      similar behaviour was observed for total T4 and free T4 plasma concentrations.
      Interestingly, a clearcut clinical amelioration was observed in both patients
      even before a reduction of circulating free thyroid hormone concentrations could
      be documented. In conclusion, our experience indicates that plasmapheresis may be
      useful in order to obtain a rapid amelioration of severe clinical picture of
      thyrotoxicosis, but cannot be considered as a definite therapy in AIIT. It should
      be considered that plasmapheresis is not devoid of risks and is also a very
      expensive procedure.

PMID- 8144858
TI  - Smoking a risk factor for hypothyroidism [correction of hyperthyroidism].

PMID- 8144859
TI  - Estrogen status and bone mass in the premenopausal period: is osteoporosis a
      developmental disease?

PMID- 8144860
TI  - Immunoscintigraphy with anti-chromogranin A antibodies in patients with
      endocrine/neuroendocrine tumors.

PMID- 8144861
TI  - Effects of hydroxyurea and cyclic adenosine monophosphate/protein kinase A
      inhibitors on the expression of the human chorionic gonadotropin alpha subunit
      and c-myc genes in choriocarcinoma.
AB  - We have previously shown that treatment of choriocarcinoma cells with
      methotrexate or hydroxyurea leads to both cessation of cell growth, accompanied
      by repression of c-myc oncogene expression, and induction of genes associated
      with the placental phenotype, including both subunits of human chorionic
      gonadotropin (hCG) and placental alkaline phosphatase. Since the genes induced by
      these antimetabolites are also cyclic AMP inducible, we hypothesized that these
      antimetabolites may cause activation of the cyclic AMP/protein kinase A pathway,
      suppressing genes associated with cellular proliferation and inducing placental
      gene expression. Three inhibitors of the cyclic AMP/protein kinase A pathway were
      assayed for their ability to inhibit the induction of the human chorionic
      gonadotropin alpha gene by hydroxyurea, and none of these inhibitors eliminated
      this induction. In addition, blockade of the cyclic AMP/protein kinase A pathway
      did not reverse the suppression of c-myc by hydroxyurea. The results of the
      inhibitor studies suggest that hydroxyurea acts independently of the protein
      kinase A pathway to stimulate gene expression, and that suppression of c-myc is
      insufficient to cause the induction of the human chorionic gonadotropin alpha
      gene by hydroxyurea.

PMID- 8144862
TI  - Short-term effects of somatostatin analogue (SMS 201-995) on left ventricular
      function in healthy persons: a scintigraphic study.
AB  - Since somatostatin has been reported to have a negative inotropic and
      chronotropic effect on atria and positive inotropic effect on ventricle, present
      study was designed to investigate the acute effects of somatostatin analogue SMS
      201-995 infusion on the left ventricular function in healthy volunteers. After
      labeling the autologous red blood cells with 750-1000 MBq 99mTc-pertechnetate,
      ECG-gated radionuclide ventriculography was performed. Using Fourier analysis of
      the left ventricular time-activity curve, ejection fraction (EF), peak ejection
      rate (PER), peak filling rate (PFR), time to end-systole (TES) and normalized
      TES/T values were calculated. Study group consisted of 12 healthy volunteers.
      Somatostatin analogue SMS 201-995 infusion was given at a rate of 100
      micrograms/h during 2h. Baseline, 1st, 2nd h and 4th h imagings were done using
      the same protocol. Simultaneously heart rate and blood pressure were recorded.
      The difference between parameters was tested using Kruskall-Wallis test. The mean
      heart rate, systolic and diastolic blood pressures and did not show any
      statistically significant change during the somatostatin analogue infusion and 2h
      later in comparison to baseline values. The mean PER and PFR had a slight
      decrease at the first hour of infusion, but the change was not significant.
      However, the significant correlation of PER values with heart rate, EF and TES
      observed at baseline study were disappeared during the infusion. These results
      indicate that somatostatin analogue infusion does not appear to change the left
      ventricular systolic and diastolic function in healthy persons significantly.

PMID- 8144863
TI  - Preventive effects of azathioprine (AZA) on the onset of diabetes mellitus in NOD
      mice.
AB  - We have studied the effects of long-term treatment with azathioprine (AZA) vs
      cyclosporin A (CSA) vs placebo (PL), in three groups of 10 week old, prediabetic
      NOD mice. One of 8 AZA, none of 8 CSA and 7 of 11 PL treated mice developed overt
      diabetes (IDDM). Quantitative morphometric analysis conducted on mouse pancreatic
      histologic sections documented that extent and degree of islet beta-cell damage
      were incomparably less severe in the mice that received AZA or CSA compared to
      those treated with PL. Since early and prolonged treatment with AZA seems to
      prevent the onset of DM in NOD mice as nearly effectively as CSA, AZA, which is
      significantly safer than CSA, could replace the latter as a potential approach
      for the immunotherapy of IDDM.

PMID- 8144864
TI  - Absence of clinically overt atherosclerotic vascular disease and adverse changes
      in cardiovascular risk factors in 70 patients with insulinoma.
AB  - Hyperinsulinemia has been assumed to contribute to the pathogenesis of
      atherosclerosis. To assess the reliability of such claim we planned a
      retrospective study on a cohort of patients with pancreatic insulin producing
      neoplasm. A correlation was sought between fasting insulin plasma levels and the
      metabolic profile emerging from those parameters known to be cardiovascular risk
      factors, i.e. plasma triglycerides and cholesterol, insulin resistance,
      hypertension. Special attention was paid to the duration of disease, because the
      time exposure to hyperinsulinemia could play an important role in developing
      cardiovascular disease. Seventy patients, 41 females and 29 males, aged 44.9 +/-
      1.96 yr (range 15-80), with surgically proved insulinoma were included in the
      study. Chronic exposure to hyperinsulinemia was documented through the
      measurement of insulin plasma levels either in the fasting state or post
      prandially, resulting in 44.7 +/- 3.28 and 149.9 +/- 12.22 microU/ml,
      respectively. Fasting glycemia in average was 45.3 +/- 1.34 mg/dl. Plasma
      triglycerides and cholesterol concentrations were 136.3 +/- 7.93 and 195.8 +/-
      5.18 mg/dl, respectively, their distribution overlapping that anticipated for the
      general population. No correlation arose between the degree of hyperinsulinemia
      and the lipidic profile. Preoperative blood pressure was 136.9 +/- 2.87 mmHg,
      systolic and 81.9 +/- 1.32 mmHg, diastolic. Hypertension was present in 5 (7.1%)
      out of 70 patients and persisted after tumor removal. A condition of insulin
      resistance (M = 4.06 +/- 0.4 mg/kg min vs 7.41 +/- 0.21) was documented through
      the euglycemic hyperinsulinemic clamp technique in 20 patients and showed a
      positive and significant correlation with fasting insulinemia.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8144865
TI  - Organ-specific autoimmunity in patients with premature ovarian failure.
AB  - The diagnosis of premature ovarian failure (POF) was made in 45 women (aged 14 to
      39 yr) with high concentrations of FSH and LH. Sera from these patients and a
      control group of 28 women were used to detect organ-specific autoantibodies.
      Eighteen patients with POF (40%) were positive for at least one autoantibody. In
      the control group only one woman (3.6%) showed autoimmunity. Antithyroid was the
      most representative autoimmunity (20%) in the POF group. By indirect
      immunofluorescence, only one patient was positive for antiovarian and antiadrenal
      antibodies. In summary, the results of this study are consistent with previous
      immunohistochemical data which indicate that autoimmune disorders are common in
      patients with POF. Furthermore, the detection of antiovarian antibodies in only
      one patient confirms that they are probably detectable in a short period of the
      disease.

PMID- 8144866
TI  - Growth hormone treatment in adults with GH deficiency: effects on new biochemical
      markers of bone and collagen turnover.
AB  - Serum bone Gla protein (BGP) and bone alkaline phosphatase (B-AP), markers of
      bone formation, carboxyterminal cross-linked telopeptide of type I collagen
      (ICTP), marker of bone resorption, and aminoterminal propeptide of type III
      procollagen (PIIINP) levels, index of collagen synthesis, were determined in 8
      adults (mean age +/- SE: 29.6 +/- 1.2 yr) with childhood onset GHD before and
      after 3 and 6 months of recombinant GH treatment (0.5 IU/kg/week). Before
      treatment, mean BGP (3.8 +/- .5 ng/ml) and B-AP (44.9 +/- 6.9 IU/L) were
      significantly (P < 0.001 and p < 0.05, respectively) lower than those recorded in
      normals (5.4 +/- 0.1 ng/ml and 61.8 +/- 1.9 IU/L, respectively), while serum ICTP
      and PIIINP levels were similar to those found in controls (ICTP: 4.7 +/- 0.8 vs
      4.1 +/- 0.3 ng/ml; PIIINP: 3.7 +/- 0.6 vs 3.2 +/- 0.2 ng/ml). BGP and ICTP levels
      significantly (p < 0.005) increased after 3 (28.4 +/- 5.3 ng/ml and 17.5 +/- 2.8
      ng/ml, respectively) and 6 months (25.1 +/- 5.0 ng/ml and 15.0 +/- 1.9 ng/ml,
      respectively) of recombinant GH treatment. B-AP levels significantly (p < 0.01)
      increased during the treatment (basal: 44.9 +/- 6.9 IU/L, 3rd month: 173.6 +/- 40
      IU/L, 6th month: 194.4 +/- 40 IU/L), while non B-AP levels remained similar to
      those recorded in basal condition. Serum PIIINP levels significantly (p < 0.0001)
      rose up after 3 (12.5 +/- 1.4 ng/ml) and 6 months (10.2 +/- 0.8 ng/ml). Serum BGP
      and ICTP levels were directly (r = 0.85, p < 0.001; r = 0.53, p < 0.01)
      correlated with serum IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8144867
TI  - Growth hormone response to oral clonidine test in normal and short children.
AB  - We evaluated the growth hormone (GH) response to an acute clonidine test (0.15
      mg/m2 po) in 30 normal prepubertal children (stature between the 3rd and 97th
      centile), in 29 short children (stature < 3rd centile for age) with height
      velocity (HV) > 10th centile and in 20 short children with HV < 10th centile. The
      three groups had comparable chronological ages. After clonidine administration
      mean peak GH levels were similar in the three groups (19.4 +/- 9.8, 17.7 +/- 8.8
      and 14.6 +/- 8.9 micrograms/l, mean +/- SD, respectively). By choosing 10
      micrograms/l as the limit for a normal response we found that stimulated GH
      levels had a sensitivity of 50% and a specificity of 83% in identifying children
      with suspected GHD (short children with subnormal HV). The diagnostic accuracy
      was almost superimposable, for cut-off values of 10 and 12 micrograms/l. Eight of
      the 10 children with subnormal HV and a GH peak < 10 micrograms/l had a GH peak <
      10 micrograms/l also after a second stimulation test. Six of the 29 short
      children with normal HV had a GH peak < 10 micrograms/l. Only one of them had a
      GH peak < 10 micrograms/l after a second stimulation test. Five of the normal
      children had peak GH levels < 10 micrograms/l. These results indicate that HV is
      a useful variable to predict the GH response to an acute GH stimulus, since the
      great majority of children with a normal growth rate had a normal GH response to
      at least one stimulation test.

PMID- 8144868
TI  - Two cases of Graves' disease with presentation of unilateral diffuse uptake of
      radioisotopes.
AB  - We present two cases of Graves' disease whose initial thyroidal scintiscan with
      99mTcO4- (Case 1) and 123I (Case 2) showed unilateral diffuse uptake of
      radioisotopes. Initial diagnosis was possibility of malignancy in Case 1 and
      Graves' disease or Plummer's disease in Case 2. Both cases underwent right
      hemithyroidectomy. Histopathology of the resected thyroid gland in both showed
      hyperplastic columnar epithelium and infiltrative lymphocytes which was
      compatible with Graves' disease. Twenty seven (Case 1) and eight months (Case 2)
      after operation, both presented with thyrotoxic symptoms associated with enlarged
      left lobe, increased serum free thyroid hormone concentrations, suppressed TSH
      concentration, increased thyroidal 123I uptake in the remaining left lobe, and
      positive thyrotropin receptor antibodies. Both cases were successfully treated
      with methimazole. It was concluded that initial radioisotope uptake as well as
      scintigram in rare subgroup of patients with Graves' disease could be similar
      with that of non-autoimmune autonomous goiter (Plummer's disease).

PMID- 8144869
TI  - Association of multinodular goiter with breast carcinoma: Cowden's disease.
AB  - Cowden's Disease or multiple hamartoma syndrome is an autosomal dominant
      genodermatosis associated with abnormalities of the breast, thyroid gland,
      gastrointestinal tract and genitourinary system. A large percentage of these
      patients have goiters or other thyroid abnormalities. Physicians should consider
      the diagnosis of Cowden's disease in patients presenting with thyroid disease and
      skin lesions such as papules or skin tags and if present these subjects should be
      screened for other malignancies associated with this disease.

PMID- 8144870
TI  - Molecular heterogeneity of a Graves' thyroid-infiltrating T cell population rich
      in CD8+ and gamma delta+ T cells.
AB  - We report here on the isolation and repertoire characterization of a Graves'
      thyroid T cell population which, unlike most Graves' thyroid T cell isolates
      reported before, was rich in CD4-CD8- T cells (16%, all TcR gamma delta+) and
      CD8+ T cells (75%) [TcR alpha beta+ (59%) and TcR gamma delta+ (16%)]. Only 7% of
      the isolated T cells were CD4+. By contrast, < 2% of peripheral blood mononuclear
      cells from the same patient were gamma delta+ and < 14% were CD8+. Sequence
      analysis of 18 TcR delta cDNAs prepared from these cells indicated the presence
      of at least 17 different gamma delta+ T cell clonotypes with molecularly
      heterogeneous antigen-binding site sequences. As opposed to most peripheral blood
      gamma delta+ T cells (express V delta 2 TcRs), 13 of the 17 different TcR delta
      clonotypes used a V delta 1 gene, although PCR amplification of TcR gamma- and
      TcR delta-specific cDNAs with V delta- and V gamma-gene family-specific
      oligonucleotides confirmed usage of all 4 V gamma and all 6 V delta families.
      Sequence analysis of 21 TcR alpha cDNAs from a TcR alpha-specific cDNA library
      indicated the presence of at least 12 different clonotypes, using 8 different V
      alpha gene families and heterogeneous antigen-binding site sequences. These
      results are in contrast with the selective V alpha gene usage reported for other
      intrathyroidal T cell subpopulations in autoimmune thyroid disease.

PMID- 8144872
TI  - Thymic nurse cells are sites of thymocyte apoptosis.
AB  - Thymic stromal cells play important roles in thymocyte differentiation and
      selection. Thymic nurse cells (TNC) are thymic epithelial stromal cells that
      envelop two to 200 CD4+CD8+ thymocytes (TNC-T). The mechanism by which TNC
      complexes form and their role in thymocyte development are unknown. TNC have been
      implicated as specialized microenvironments for proliferation, positive
      selection, negative selection, and apoptosis. Using TCR-gamma junctional sequence
      analysis of thymocytes within individual TNC, eight of ten TNC analyzed were
      polyclonal, and two showed evidence of oligoclonality. TCR-alpha beta expression
      was not detectable on most TNC-T and SCID mice, which do not express TCRs because
      of a defect in TCR gene rearrangement, had normal numbers of thymocyte-bearing
      TNC. Thus, TCR expression is not necessary for TNC formation. Treatment of mice
      with Abs to CD3 epsilon, which induces apoptosis in immature thymocytes, resulted
      in an eightfold increase in TNC per thymus with 95.5% apoptotic TNC-T. These
      results suggest that a function of TNC is the clearance of nonfunctional,
      nonselected, apoptotic thymocytes.

PMID- 8144871
TI  - Hirsutism and the effectiveness of spironolactone in its management.

PMID- 8144873
TI  - IFN-gamma, TNF, and IL-6 production by vaccinia virus immune spleen cells. An in
      vitro study.
AB  - The production of cytokines by virus immune spleen cells after in vitro
      restimulation was investigated. Vaccinia virus-primed spleen cells from CBA/H
      mice were stimulated in vitro with virus-infected UV-irradiated syngeneic cells.
      Both CD4+ and CD8+ T cell populations proliferated after restimulation. TNF, IL
      6, and IFN-gamma were detected within 12 h of restimulation with maximal levels
      reached by 24 h. Adherent cells were major producers of IL-6 and TNF, whereas IFN
      gamma production was dependent on CD4+ T cells and adherent cells. The IFN-gamma
      response was Ag specific, whereas the production of TNF and IL-6 was not.
      Stimulation with vaccinia virus constructs encoding IFN-gamma or TNF altered the
      levels of cytokines produced, in that IFN-gamma expression by stimulator cells
      led to increased IFN-gamma production, whereas TNF expression by stimulator cells
      augmented both TNF and IFN-gamma production by responder cells.

PMID- 8144874
TI  - Changes in glucose transport and transporter isoforms during the activation of
      human peripheral blood lymphocytes by phytohemagglutinin.
AB  - We have explored the mechanism of stimulation of glucose transport during PHA
      stimulation of human peripheral blood lymphocytes (HPBT) enriched in T cells.
      Equilibrium exchange flux of 3-O-methyl glucose (3-O-MG) was stimulated two- and
      fourfold at 24 and 48 h after PHA stimulation, respectively. The increase was
      transient in that the flux rate returned to control (unstimulated) levels by 96
      h. Immunoblotting and immunoprecipitation using specific Abs revealed that
      resting HPBT expresses glucose transporter isoforms GLUT-2 and GLUT-3 but not
      GLUT-1. After PHA stimulation, GLUT-1 expression was induced predominantly in the
      plasma membrane, whereas GLUT-3 expression was simultaneously down-regulated.
      GLUT-1 expression was detectable at 24 h, peaked at 48 h, and disappeared at 96
      h. The total number of glucose transporters per cell measured as the total
      capacity of D-glucose displaceable cytochalasin B binding did not change
      significantly at any time after PHA stimulation. PHA stimulation also caused
      expression of high affinity IL-2R and secretion of IL-2. The IL-2 secretion was
      transient, which peaked at 24 h, slightly preceding the GLUT-1 expression peak
      and disappeared at 72 h. In PHA-activated HPBT cells synchronized at G0-G1, GLUT
      1 was not expressed but was rapidly induced by exposure to IL-2. This induction
      did not occur in the presence of cyclosporin A, which inhibits IL-2 secretion.
      Based on these observations, we conclude that PHA stimulation increases glucose
      transport partly by inducing the expression of GLUT-1 instead of GLUT-3 and that
      GLUT-1 expression is induced by signals generated by IL-2 binding to its high
      affinity receptors.

PMID- 8144875
TI  - Expression of the NK-TR gene is required for NK-like activity in human T cells.
AB  - NK cells lyse target cells without previous immune sensitization. A small subset
      of T cells also exhibits NK-like activity, which is distinct from TCR-mediated,
      MHC-restricted, and MHC-unrestricted cytotoxicity. We recently cloned a gene, NK
      TR, which is postulated to be part of the NK target-recognition/triggering
      complex. To determine whether the NK-TR gene product is requisite for NK-like
      killing, stable antisense transfectants were generated by using a human T cell
      clone with NK-like activity. Two distinct antisense regions of the sequence were
      used to generate the transfectants alpha NK-TR and alpha Cyclo. Transfectants
      lost the ability to lyse NK-sensitive targets but did not lose lectin-mediated
      cytotoxic activity. This effect was not seen with the control vector transfectant
      cell line. The loss of NK-like activity by the antisense transfectant alpha NK-TR
      correlated with the specific decrease in endogenous NK-TR mRNA and protein. These
      results demonstrate the requirement for the NK-TR protein for NK-like killing.
      Moreover, the results have important implications for examining developmental
      relationship between T and NK cells and the possible roles for T cells with NK
      like activity in vivo.

PMID- 8144876
TI  - IL-4 is essential for the systemic transfer of delayed hypersensitivity by T cell
      lines. Role of gamma/delta cells.
AB  - Hapten (trinitrophenyl)-specific T cell lines were obtained by repeated
      stimulation of lymph node cells from immune mice with Ag in vitro. These T cell
      lines show phenotypic properties and a pattern of cytokine production typical of
      Th1 cells and consisted of more than 90% V beta 8.2+ T lymphocytes and 6 to 9%
      gamma/delta + T lymphocytes. The lines mediate a local passive transfer of DTH
      when injected at the site of Ag challenge but fail to mediate a systemic passive
      transfer of DTH when injected i.v. However, a successful systemic passive
      transfer of DTH was observed when IL-4 was given to recipient mice together with
      the T cell lines or when the T cell lines were incubated in vitro with IL-4. IL-4
      enables systemic, specific passive transfer of DTH at a dose of 10 pg/ml in vitro
      and at a dose of 10 pg/mouse in vivo; it is effective when injected 4 h before
      cell transfer but not when given 1 to 5 days earlier. Cytofluorimetric analysis
      shows that the gamma/delta + cells and not the V beta 8.2+ cells of the line
      express IL-4R and a good systemic transfer of DTH is observed when gamma/delta +
      cells are incubated in vitro with IL-4 and then injected together with V beta
      8.2+ cells into recipient mice. In contrast, injection of V beta 8.2+ cells
      treated with IL-4 together with gamma/delta + cells fails to transfer DTH.
      Overall, the present results show that IL-4 is an important mediator in the DTH
      reaction and that gamma/delta + cells are one of the targets of its action.

PMID- 8144877
TI  - Expression of functional trk tyrosine kinase receptors after T cell activation.
AB  - Increasing evidence indicates that nerve growth factor (NGF), in addition to its
      neurotrophic actions, exerts specific effects on cells of the immune system. This
      report show that the CD4-positive T cell line 9/6 expresses trk protooncogene,
      the signal transducing receptor unit for NGF, after TCR-mediated activation by Ag
      and APC. This receptor is of functional importance because interaction of NGF
      with Ag-stimulated 9/6 T cells induced the transcriptional activation of the c
      fos gene, a hallmark of the biochemical response to NGF. Our findings that
      neither mitogen nor Ag stimulation induced the expression of the low affinity NGF
      receptor in 9/6 T cells indicate that trk alone is sufficient to mediate biologic
      activity of NGF in T lymphocytes.

PMID- 8144878
TI  - Expression of v-src in T cells correlates with nuclear expression of NF-kappa B.
AB  - NF-kappa B is a rapidly inducible transcriptional activator that responds to a
      variety of signals and influences the expression of many genes involved in the
      immune response. Protein tyrosine kinases transmit signals from cytokine and
      immune receptors. Very little information exists linking these two important
      classes of signaling molecules. We now demonstrate that v-src expression
      correlates with nuclear expression of a kappa B binding complex similar to that
      induced by phorbol ester and ionomycin, as detected by electrophoretic mobility
      shift assay using a variety of kappa B sites. This complex was blocked by the
      tyrosine kinase inhibitor, herbimycin A. The v-src-induced complex comprised the
      p50 and p65 components of NF-kappa B, as determined by supershift and immunoblot
      analysis. As a functional correlate of this finding, transient co-transfection of
      HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src
      activated this promoter in a kappa B-dependent manner. We found that
      transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the
      proximal, rather than the distal, kappa B element. The implications for T cell
      receptor signaling and HIV-1 gene expression are considered.

PMID- 8144879
TI  - Antigen presentation in the central nervous system. The inhibitory effect of IL
      10 on MHC class II expression and production of cytokines depends on the inducing
      signals and the type of cell analyzed.
AB  - Cells of the macrophage lineage are required to cope with bacterial infection and
      to serve as APC for T lymphocytes. Among the regulatory factors limiting the
      macrophage response to infection and the expansion of Ag-specific T cells, IL-10
      has received recent attention. On monocytes/macrophages, IL-10 has been shown to
      inhibit the intracellular killing of bacteria, the secretion of cytokines, and
      the expression of MHC molecules. In the present study we have examined the effect
      of IL-10 on different APC obtained from the central nervous system. Both,
      astrocytes and microglial cells are in a resting state and require activation
      signals to express MHC class II and cytokine genes. Whereas IL-10 profoundly
      inhibits the IFN-gamma-induced expression of MHC class II Ag on microglial cells,
      it had no such effects on astrocytes. Nevertheless, IL-10 suppressed the MHC
      class II- and Ag-dependent proliferative response of T cells in the presence of
      both types of APC. As shown by the use of anti-IL-10 Abs, endogenously produced
      IL-10 influenced the function of microglia but not of astrocytes to serve as APC.
      IL-10 significantly inhibited the LPS-induced production of granulocyte
      macrophage-CSF, macrophage-CSF, and IL-6 by both astrocytes and microglial cells.
      In contrast, the secretion of these cytokines by the two glial cell population
      was not altered by IL-10 when IL-1 beta, TNF-alpha, or viruses were used as
      stimuli.

PMID- 8144880
TI  - HLA class I molecules are not transported to the cell surface in cells infected
      with herpes simplex virus types 1 and 2.
AB  - To assess the effect of herpes simplex virus (HSV) on assembly and transport of
      class I MHC molecules, we compared class I MHC immunoprecipitated from
      metabolically labeled infected and uninfected human dermal fibroblasts. The
      immunoprecipitates were analyzed by isoelectric focusing, allowing identification
      of individual class I alleles and assessment of transport through the Golgi
      apparatus by the sialation of carbohydrate residues. In cells infected with wild
      type HSV, class I synthesis was reduced or abolished because of the host protein
      synthesis shutoff function of the UL41 gene product. In cells infected with
      mutant viruses of both HSV-2 strain G and HSV-1 strain 17 that lack the UL41
      gene, class I HLA molecules failed to become sialated, suggesting that they were
      not transported to the Golgi apparatus. In contrast, transferrin receptor was
      normally sialated in both infected and uninfected cells. Drug treatments of cells
      to restrict viral gene expression suggested that an early gene or genes were
      responsible for the effect. A pulse chase showed that class I molecules were
      synthesized in normal amounts in infected cells, but that heavy chains were
      retained in a sialyl transferase negative compartment either stably associated
      with beta 2m or as free heavy chain in a pattern that is characteristic for each
      class I allele. HSV is thus the fourth example of a DNA virus that interferes
      with class I assembly or transport.

PMID- 8144881
TI  - Identification of a 52-kDa molecule (p52) coprecipitated with the Ig receptor
      related MB-1 protein that is inducibly phosphorylated by the stimulation with
      phorbol myristate acetate.
AB  - Triggering of the Ig receptor (IgR) induces the activation in multiple
      intracellular signal transduction reactions including protein tyrosine
      phosphorylation, activation of phospholipase C, increased inositoltriphosphate,
      increased diacylglycerol, intracellular Ca2+ mobilization, and activation of
      protein kinase C. The IgR-complex, composed of mu-chain, L chain, Ig-alpha (MB
      1), and Ig-beta (B29) proteins, is a functional unit both for expression of IgR
      and for signal transduction into cells, possibly by physical association with the
      down-stream functional molecules. An important functional motif ((D or E)-X7-(D
      or E)-Y-X3-L-X7-Y-X2-(L or I)) in the cytoplasmic domain of MB-1 molecule was
      shown to bind with several phosphoprotein components including src-type tyrosine
      kinases and phosphatidylinositol-3 kinase. To further study the functional
      components, we analyzed the phosphoprotein molecules coprecipitated with MB-1
      protein. We found that a 52-kDa protein is coprecipitated with MB-1 protein and
      is inducibly phosphorylated by the stimulation with PMA. A rat mAb, prepared by
      immunizing the 52-kDa protein purified from SDS-PAGE, could detect the similar 52
      kDa phosphoprotein (p52) expressed on the cell surface. In comparison with the 52
      kDa protein in the immunoprecipitate of MB-1, the p52 migrated to the same
      position on 2-D gel electrophoresis (nonequilibrium pH gradient gel
      electrophoresis/SDS-PAGE). An in vitro kinase reaction analysis demonstrated that
      the p52 is tightly associated with the tyrosine kinase molecule(s), one of which
      is an 80-kDa protein containing an apparent autophosphorylation activity. These
      molecules would provide the informations of the down-stream molecules in the
      cascade reactions of the IgR-mediated signal transduction.

PMID- 8144882
TI  - Generation and characterization of a monoclonal antibody that inhibits stromal
      cell-dependent B lymphopoiesis.
AB  - We generated a mAb, R4, against a stromal cell line, ST2, which is one of several
      stromal cell lines that can support in vitro B lymphopoiesis. Flow cytometry
      studies using R4 revealed that R4 reacted with several stromal, fibroblast, and
      some B cell lines, but not with freshly isolated bone marrow cells, splenocytes,
      thymocytes, or T cell lines. R4 could immunoprecipitate a M(r) = 24-kDa protein
      (p24) and a M(r) = 55-kDa protein (p55) from a stromal cell line and a B cell
      line, respectively. R4 inhibited the development of B cell progenitors from bone
      marrow cells in cultures supported by stromal cell lines, ST2, or op/op
      fibroblast line, but did not inhibit myelopoiesis supported by ST2. R4 also
      inhibited the growth of a stromal cell-dependent pre-B cell line, DW8, but not of
      two stromal cell-independent B cell lines, 70Z/3 and M12, despite the fact that
      R4 reacted all three of these lines. Because R4 inhibited B lymphopoiesis in the
      transwell culture where stromal cells are not allowed to contact pre-B cells, R4
      Ag may not directly affect cellular contact. In vivo treatment of pregnant mice
      with R4 caused a reduction in the number of B cell progenitors in the bone
      marrows of some of the newborn offspring.

PMID- 8144883
TI  - Role for MHC class I molecules in selecting and protecting high affinity peptides
      in the presence of proteases.
AB  - Ag fragments derived from the cytosol are transported into the endoplasmic
      reticulum (ER) lumen, where they bind to nascent MHC class I molecules. However,
      it is not known whether only high affinity peptides enter the ER, or whether ER
      proteases must trim longer precursor peptides down to optimal size. To evaluate
      the feasibility of proteolytic fine trimming in vitro, soluble Kd and Kb were
      preincubated with peptides that bind to Kd or Kb and the mixture was exposed to
      three different proteases. Class I protected allele-specific peptides against
      proteolysis, whereas the other peptides were degraded to the amino acid level.
      When a Kd/S11E (SYIPSAEYILE) complex was immunoprecipitated after incubation with
      carboxypeptidase, both S11E and the optimal sized S9I (SYIPSAEYI) were found to
      be specifically bound to Kd. However, only S91 was recovered if S11E, Kd and
      carboxypeptidase were mixed at the same time, and there was no fine-trimming of
      bound S11E if high protease concentrations and short proteolysis times were used,
      which suggests that trimming occurs only in the unbound state. The amount of
      peptide that immunoprecipitated with Kd increased after carboxypeptidase
      treatment of Kd/S11E, implying that the peptide affinity had increased. Kd also
      protected S9I against proteolysis by a lysed microsome preparation, demonstrating
      that class I could also protect high affinity peptides in vivo. These results
      suggest that class I participates in the selection of high affinity peptides in
      the ER, by sampling transported unbound peptides are degraded by ER proteases or
      efflux back to the cytosol.

PMID- 8144884
TI  - Differential activation of p21ras in CD45RA+ and CD45RO+ human T lymphocytes.
AB  - CD45RA+ and CD45RO+ human T cells differ in their functional responses to
      different forms of mitogenic stimulation. However, little is known about the
      intracellular signaling events related to the functional differences in these two
      subsets. In the present study, we examined the ability of different Abs to the
      TCR/CD3 complex to activate the p21ras proto-oncogene product in CD45RA+ and
      CD45RO+ T cells. Stimulation with soluble OKT3 anti-CD3 mAb induced activation of
      p21ras in CD45RA+ cells but not in CD45RO+ cells, although soluble anti-CD3 was
      able to induce both activation of CD3-associated kinases and IL-2 responsiveness
      in CD45RO+ cells. Similar results were obtained by using UCHT1, a different anti
      CD3 Ab. In contrast, cross-linked anti-CD3 or the combination of phorbol ester
      and ionomycin were found to activate p21ras equally in both T cell subsets. Our
      results demonstrate a selective inability of CD45RO+ human T cells to activate
      p21ras in response to soluble anti-CD3 mAb.

PMID- 8144885
TI  - Point mutations define a mIgM transmembrane region motif that determines
      intersubunit signal transduction in the antigen receptor.
AB  - Ag binding to the membrane Ig (mIg) substructure of the B cell Ag receptor leads
      to activation of cytoplasmic effector molecules including blk, fyn, lyn, and/or
      lck tyrosine kinases that are associated with receptor's dimeric Ig-alpha/Ig-beta
      transducer substructure. The structural basis of the apparent intermolecular
      transmission of this information within the receptor complex is unknown. Here we
      report that conservative point mutation of a sequence, S584-K597, at the
      cytoplasmic end of the predicted transmembrane spanning domain of the mIgM heavy
      chain (mu) ablates Ag-activated signal transduction, while having no detectable
      effect on association of mIgM with Ig-alpha/Ig-beta heterodimers. Specifically,
      mutation of serine584 to alanine, tyrosine587 to phenylalanine, threonine592 to
      valine, or lysine597 to isoleucine completely abrogated Ag-induced signal
      transduction leading to protein tyrosine phosphorylation and Ca2+ mobilization.
      Interestingly, mutants in the more peripheral of these residues, serine584 to
      alanine and lysine597 to isoleucine, remained responsive to a monoclonal
      antireceptor Ab (b-7-6) and all mutants remained responsive to polyclonal
      antireceptor Ab. These data implicate the polar sequence, -Y587STTVT592-, in
      transfer of information from ligand binding to transducer substructures within
      this heterooligomeric receptor complex. They further indicate that receptor
      activation by ligands that bind with high affinity and/or to constant region mIg
      epitopes is less dependent on the integrity of this motif.

PMID- 8144886
TI  - Cyclosporin A inhibits positive selection and delays negative selection in alpha
      beta TCR transgenic mice.
AB  - Cyclosporin A (CsA) is an immunosuppressive drug that inhibits TCR-mediated
      signal transduction. This drug has two major effects on developing alpha beta
      thymocytes in normal mice: it blocks the development of most mature CD4+8- and
      CD4-8+ thymocytes and inhibits the deletion of some but not all self-specific
      thymocytes. The latter effect may explain how CsA treatment can paradoxically
      induce autoimmunity in certain situations. Here we investigated the effects of
      CsA on thymocyte development in transgenic mice that express on most of their T
      cells an alpha beta TCR specific for male H-Y Ag bound to H-2 Db class I
      molecules, a model system in which positive and negative selection have been
      clearly defined. Positive selection occurs in female mice, resulting in the
      development of mature CD4-CD8+ T cells, whereas negative selection occurs in male
      mice, resulting in the deletion of self-reactive CD4+8+ thymocytes. CsA blocked
      positive selection, as evidenced by the finding that most of the cells present in
      the thymuses of CsA-treated female mice were functionally immature precursors
      that expressed heat-stable Ag. In male mice, CsA delayed but did not prevent the
      deletion of most CD4+8+ thymocytes. A few transgenic thymocytes, however, were
      not deleted and achieved the TCR+, CD4-8+ phenotype of positively selected cells.
      Therefore, for a small subset of thymocytes, CsA may convert a normally
      negatively selecting TCR signal to a positively selecting one.

PMID- 8144887
TI  - Gene required for normal MHC class II expression and function is localized to
      approximately 45 kb of DNA in the class II region of the MHC.
AB  - In certain mutant human B cell lines, MHC-encoded class II molecules displayed at
      the cell surface have an abnormal conformation and are unstable in the presence
      of SDS. The mutants cannot present exogenous protein Ags to T cells but elicit
      responses with exogenous antigenic peptides; thus, formation of intracellular
      complexes between antigenic peptides and class II molecules is impaired. Previous
      analysis of LCL deletion mutants, .82, .174, and 5.2.4, showed that genes needed
      for this function must be present in approximately 230 kb of DNA in the class II
      region of the MHC. We now describe a new deletion mutant, .61, which has normal
      class II-mediated Ag processing/presentation. The TAP1, TAP2, LMP2, and LMP7
      genes are deleted from .61, demonstrating that those genes are not needed for
      normal formation of intracellular class II/peptide complexes. The genes in
      question must be located in DNA that is present in .61 and .82 (both normal) and
      absent from .174 and 5.2.4. (both defective). Mapping of the deletion breakpoints
      indicates that genes needed for normal class II-associated Ag
      processing/presentation are either: 1) in an approximately 40 kb L DNA segment
      located between the DMB and LMP2 loci or 2) in an R region between the DQA2 and
      DQB1 loci and are completely included on a 5.1-kb fragment formed by joining of
      DNA that flanks the deletion in .61. The evidence favors location of the genes in
      the L DNA segment.

PMID- 8144888
TI  - Naturally processed peptides longer than nine amino acid residues bind to the
      class I MHC molecule HLA-A2.1 with high affinity and in different conformations.
AB  - An equilibrium binding assay was used to directly measure the relative affinities
      of naturally processed 9-mer, 10-mer, and 12-mer peptides for the human class I
      MHC molecule HLA-A2.1. The peptides exhibited a range of affinities with IC50
      values of 11 to 214 nM. The mode of interaction between these peptides and HLA
      A2.1 was examined using peptides in which Asp had been substituted for suspected
      anchor residues. Regardless of length, the previously identified Leu at position
      2 relative to the amino terminus was critical for peptide binding. While the
      carboxyl terminal residue was also critical for the binding of a 9-mer peptide,
      it was much less important in the binding of longer peptides. Additional residues
      close to the carboxyl terminus that contained aliphatic hydrocarbon side chains
      were of similar or greater importance in peptide binding. In addition, residue at
      position 3 also appeared to be important for the binding of longer peptides. The
      data suggest that different naturally occurring longer peptides can bind in
      different conformations to class I MHC molecules. While one of these is similar
      to the kinked conformation described by others, another conformation would
      involve an extension of the carboxyl terminus out of the class I binding site.
      The ability of MHC molecules to accommodate the same peptide in different
      conformations would appear to have distinct advantages to the immune system.

PMID- 8144889
TI  - Exploration of requirements for peptide binding to HLA DRB1*0101 and DRB1*0401.
AB  - The individual amino acid contacts responsible for peptide binding to DRB1*0101
      and/or DRB1*0401 were defined using a quantitative binding assay. The
      differential contribution of each amino acid in two well studied T cell
      determinants, HA307-319 and RMBP 90-102, was delineated by comparing the IC50
      values of analogues of varying length. This analysis confirmed the importance of
      a hydrophobic amino acid located near the amino-terminus for binding to both
      alleles and revealed that the contribution of the carboxyl-terminal amino acids
      differed between DRB1*0101 and DRB1*0401. Taking advantage of previous
      experiments demonstrating that all of the residues could be replaced with
      alanine, with the exception of the key hydrophobic amino acid, simplified
      analogues composed of polyalanines were used to prove 1) optimal binding depended
      on the position of the hydrophobic side chain relative to the amino- and carboxyl
      termini; 2) aromatic amino acids were superior to aliphatic side chains at this
      position; and 3) a significant amount of free energy of binding arises from
      hydrogen bonding between the class II binding site and the amide bonds of the
      ligand. The role of each carbonyl and amide nitrogen was measured by assaying
      analogues containing reduced peptide bonds or N-methyl amino acids. Serine, but
      not glycine, could be used as a framework amino acid for peptide ligands,
      indicating that the beneficial aspects of these simplified structures was the
      combination of retaining the correct orientation of the peptide bonds, the
      restriction of the conformational freedom by limiting the possible phi/psi angles
      of the peptide, and avoidance of deleterious side-chain contacts. Collectively,
      these data were consistent with the peptide binding in a nonrepeating
      conformation with the vast majority of the free energy of binding arising from
      hydrogen bonds with the peptide backbone and a single, key hydrophobic side chain
      interacting in a conserved pocket in both DRB1*0101 and DRB1*0401.

PMID- 8144890
TI  - Binding of C3b and C4b by the CR1-like site in murine CR1.
AB  - We determined whether the six short consensus repeats (SCRs) that are appended to
      the amino terminus of murine CR2 to form murine CR1 contain a binding site for
      C4b in addition to that for C3b, and whether these sites overlap or are distinct.
      Human K562 transfectant cell lines were established that stably expressed
      constructs encoding variable combinations of these six murine SCRs attached to
      the amino terminus of a truncated form of human CR2 lacking its iC3b/C3dg binding
      site. These cell lines, and two others expressing full-length human CR1 and SCRs
      lacking its iC3b/C3dg binding site. These cell lines, and two others expressing
      full-length human CR1 and SCRs 8-11 of the C3b binding site of human CR1,
      respectively, were assessed for their capacity to form rosettes with sheep E
      bearing rat C4b or guinea pig C3b. K562 cells with full length human CR1 formed
      rosettes with both EC3b and EC4b, and the cells expressing the construct with
      human CR1 SCRs 8-11 bound only EC3b. The murine CR1/human CR2 chimera containing
      murine SCRs 1-6 resembled the full length human CR1 in binding both EC3b and
      EC4b. Deletion of SCRs 5-6 from the murine CR1/human CR2 chimera diminished in
      parallel, but did not abolish, binding of EC3b and EC4b. Constructs containing
      SCRs 2-5, SCRs 3-6, or SCRs 2-6 lacked activity, indicating an absolute
      requirement for SCR-1 for binding of both C3b and C4b. Therefore, murine CR1
      binds both C3b and C4b, and the sites for these ligands have similar, if not
      identical, amino- and carboxyl-terminal boundaries.

PMID- 8144891
TI  - The transcription factor BSAP (NF-HB) is essential for immunoglobulin germ-line
      epsilon transcription.
AB  - Treatment of murine splenic B lymphocytes and certain B-lineage cell lines with
      mitogen (LPS) and the lymphokine IL-4 has been shown to induce expression of germ
      line epsilon transcripts (l epsilon transcripts) and class switching to the C
      epsilon gene. Three protein complexes, one of which (complex 3) is constitutively
      expressed, have been shown to bind to a 179-base pair LPS/IL-4-responsive l
      epsilon promoter (Rothman, P., S. C. Li, B. Gorham, L. Glimcher, F. W. Alt, and
      M. Boothby. 1991. Mol. Cell. Biol. 11:5551). Complex 3 is indispensable for this
      inducible promoter activity. In this report, we have used electrophoretic
      mobility shift assays (EMSA) to demonstrate that the early B cell-specific
      transcription factor (BSAP) is involved in the formation of complex 3. In
      addition, BSAP is implicated functionally in l epsilon transcription because a
      BSAP binding site either from a sea urchin histone promoter (H2A-2.2) or from 5'
      of murine immunoglobulin S gamma 2a can substitute for the epsilon-associated
      site (epsilon(foot), as assayed by transient transfection assays of the l
      epsilon:CAT reporter constructs into the M12.4.1 B cell line. Like the sea urchin
      histone BSAP site, the complex 3 binding site (epsilon(foot)) functions as an
      upstream promoter element when assayed in the OVEC vector. These results indicate
      that BSAP is an essential protein required for LPS/IL-4 induction of the l
      epsilon promoter. In addition, experiments showing that a BSAP binding site from
      5' of S gamma 2a also functions as an upstream promoter element in OVEC suggest a
      potential role for BSAP in regulation of the IgG2a isotype.

PMID- 8144892
TI  - Biased utilization of DHQ52 and JH4 gene segments in a human Ig transgenic
      minilocus is independent of antigenic selection.
AB  - We have assessed the effect of antigenic selection on human Ig heavy chain D and
      JH gene segment utilization in mice that contain transgenes composed of 2 VH (psi
      VH3-105 and VH5-251), 10 D, 6 JH, C mu, and C gamma 1 human gene segments. Human
      heavy chains using the functional VH5-251 gene segment are expressed in the serum
      and on the surface of murine B cells. The second VH gene segment (psi VH3-105) is
      not expressed as a protein but is rearranged and transcribed into mRNA. We
      previously reported that the functional VH5-251 mu transcripts preferentially
      used the DHQ52 and JH4 gene segments similar to their use in the human
      repertoire. Here, we demonstrate that the nonfunctional (psi VH3-105) gene
      segment shows the same bias in D and JH gene segment utilization. Because
      transcripts using the pseudo-VH gene segment cannot be subjected to antigenic
      selection, we conclude that the restricted repertoire observed is Ag independent.
      Analysis of pseudo VH gene segment recombination products reveals no bias in D
      gene segment reading frame utilization. Finally, we demonstrate that in the human
      transgene coding sequence complementarities can affect the recombination site and
      that D inversion is common.

PMID- 8144893
TI  - Intracellular infection by Leishmania donovani inhibits macrophage apoptosis.
AB  - The phagocytic macrophage plays a critical role in host immune responses to
      microbial infection, and represents a major source of inflammatory and growth
      cytokines. Intramacrophage infection by the protozoan parasite Leishmania
      donovani results in increased viability of the host cell in the absence of
      exogenous growth factor. We demonstrate that infection of bone marrow-derived
      macrophages (BMMs) by L. donovani promastigotes or treatment of BMMs with
      lipophosphoglycan LPG, the major surface molecule of the promastigote, inhibits
      apoptosis in the macrophage induced by the removal of macrophage (M)-CSF. This
      effect was also achieved by supernatants collected from L. donovani-infected
      macrophages, implicating the elaboration of a soluble factor by infected cells as
      the mediator of this inhibition. To identify candidate factors, reverse
      transcription PCR was employed to characterize the mRNA cytokine profile of
      infected macrophages. L. donovani infection of BMMs was found to induce gene
      expression for granulocyte-macrophage CSF, TNF-alpha, TGF-beta, and IL-6, but not
      M-CSF or IL-1 beta. Of the cytokines induced by L. donovani, rTNF-alpha and
      recombinant granulocyte-macrophage CSF were shown to inhibit apoptosis of BMMs
      induced by the removal of M-CSF. The amount of these cytokines in L. donovani
      infected cell supernatants was quantified by ELISA. The mechanism by which L.
      donovani may inhibit apoptosis is discussed.

PMID- 8144894
TI  - Membrane vesiculation of Naegleria fowleri amoebae as a mechanism for resisting
      complement damage.
AB  - Pathogenic and nonpathogenic Naegleria amoebae activate the alternative C
      pathway; however, only pathogenic amoebae are resistant to C-mediated damage. The
      present study was undertaken to determine the mechanism by which highly
      pathogenic N. fowleri amoebae resist C-mediated damage. Nomarski optics
      microscopy and electron microscopy of Naegleria amoebae revealed membrane
      blebbing on the surface of C-resistant N. fowleri, but not on C-sensitive N.
      gruberi, in response to incubation in normal human serum diluted 1:4 to 1:16.
      Immunofluorescent staining of pathogenic amoebae, by using antiserum to human C
      proteins comprising the membrane attack complex, C5b through C9, and FITC-labeled
      goat anti-rabbit IgG, confirmed that the membrane attack complex was concentrated
      on the membrane blebs. Binding studies with the use of radioiodinated C9
      demonstrated a decrease in the 125I-labeled C9 cpm associated with N. fowleri
      amoebae and an increase in the 125I-labeled C9 cpm associated with the released
      membrane vesicles after increasing incubation periods in normal human serum.
      Treatment of pathogenic, C-resistant N. fowleri with cytochalasin D or
      cytochalasin B to inhibit actin-dependent exocytic processes increased the
      susceptibility of the amoebae to C damage. In contrast, incubation of
      nonpathogenic, C-sensitive amoebae with cytochalasins did not alter their
      susceptibility to C lysis. These data indicate that pathogenic N. fowleri use
      membrane vesiculation to remove membrane-deposited C proteins, specifically the
      membrane attack complex (C5b-C9). The ability to remove surface-associated
      membrane attack complexes serves as one mechanism by which pathogenic N. fowleri
      resist C lysis.

PMID- 8144895
TI  - Neutralization of IL-8 inhibits neutrophil influx in a rabbit model of endotoxin
      induced pleurisy.
AB  - Although the potent neutrophil chemotaxin, IL-8, is a known product of endotoxin
      stimulated cells in vitro, the contribution of IL-8 to neutrophil recruitment in
      Gram-negative endotoxin inflammation in vivo is unknown. To determine whether
      neutralization of IL-8 would decrease endotoxin-induced neutrophil influx, we
      generated neutralizing mAbs to rabbit rIL-8 for use in our rabbit model of
      endotoxin-induced pleurisy. One mAb, ARIL8.2, specifically inhibited both rabbit
      rIL-8-induced chemotactic activity and activation of the rabbit IL-8 receptor
      transfected in 293 cells. Anesthetized rabbits with in-dwelling pleural catheters
      received either neutralizing mAb (ARIL8.2; 1 mg/kg) or irrelevant isotype-matched
      mAb (anti-HIV gp120) i.v. 1 h before as well as intrapleurally (20 micrograms/ml)
      at the time of intrapleural instillation of Escherichia coli endotoxin (200 ng
      bilaterally). ARIL8.2 blocked 77% of endotoxin-induced neutrophil influx (21 +/-
      2 (SE) x 10(6) (ARIL8.2) vs 91 +/- 15 x 10(6) (anti-gp120) (p < 0.0001)). By
      Western analysis, a band corresponding to rabbit IL-8 was detected in the pleural
      liquid of rabbits in both groups. By ELISA, however, the concentration of free,
      unbound IL-8 in the pleural liquid was significantly less in the ARIL8.2 group
      than in the anti-gp120 group for at least 4 h, confirming that ARIL8.2 bound the
      IL-8 generated in vivo during that time. We conclude that neutralization of IL-8
      profoundly inhibits neutrophil recruitment in endotoxin-induced pleurisy
      indicating that IL-8 is a major chemotactic factor in this model of acute
      inflammation.

PMID- 8144896
TI  - A humanized antibody specific for the platelet integrin gpIIb/IIIa.
AB  - C4G1, a murine mAb reactive with the platelet gpIIb/IIIa integrin, was humanized
      for potential treatment of thrombosis-related disorders. The variable regions of
      light- and heavy-chain cDNAs from the C4G1 hybridoma were first cloned and
      sequenced. Humanized C4G1 Ab of the IgG1 isotype was constructed by combining the
      complementarity-determining regions of C4G1 with human framework and constant
      regions. The human framework was chosen to maximize homology with the C4G1
      variable region sequence, and a computer model of C4G1 was used to aid design of
      the final framework sequence. Genetic constructs were also developed to produce
      Fab and F(ab')2 fragments of the humanized C4G1 Ab. The humanized IgG1 Ab as well
      as the Fab and F(ab')2 fragments showed equivalent binding affinities to their
      murine counterparts, indicating no loss in binding affinity during the
      humanization process. The humanized Ab and its fragments were also shown to
      inhibit platelet aggregation and to inhibit binding of fibrinogen to gpIIb/IIIa
      in vitro.

PMID- 8144897
TI  - Immunoreactivity and function of oligosaccharides in cobra venom factor.
AB  - Cobra venom factor (CVF) is the nontoxic C-activating glycoprotein in cobra
      venom. It is a structural and functional analogue of complement component C3.
      Previous work has established that the major oligosaccharide chain of CVF is a
      symmetric fucosylated biantennary complex-type N-linked chain containing an alpha
      galactosylated Le(x) antigenic epitope, Gal alpha 1-3Gal beta 1-4 (Fuc alpha 1-3)
      GlcNAc beta 1, a novel carbohydrate structure. We show that naturally occurring
      anti-alpha-Gal Ab present in normal human serum binds to CVF. In view of a
      possible human application of CVF, we studied the effect of this anti-alpha-Gal
      Ab on CVF function as well as the effect of oligosaccharide modification or
      removal on CVF activity and immunoreactivity with the anti-alpha-Gal Ab. The
      immunoreactivity of CVF with the anti-alpha-Gal Ab is abolished upon de-alpha
      galactosylation or complete deglycosylation. De-alpha-galactosylated CVF and
      deglycosylated CVF were found to be equally active in forming a stable C3/C5
      convertase with human factor B and in decomplementing human serum indicating that
      the oligosaccharide chains of CVF are not required for its C-activating function.
      Consistent with the unaltered functional activity, deglycosylation of the
      molecule caused only minor changes in secondary structure as judged by far UV
      circular dichroism analysis. However, the oligosaccharide chains appear to
      contribute to the thermal stability of CVF, because deglycosylation caused the
      molecule to be more sensitive to temperature. Inasmuch as rCVF produced in
      mammalian cells can be expected to contain sialylated oligosaccharide chains, we
      also prepared sialylated CVF by enzymatic sialylation of de-alpha-galactosylated
      and de-alpha-fucosylated CVF with 2,6-sialyltransferase. It was found that the
      secondary structure and the activity of sialylated CVF were unchanged compared to
      native CVF.

PMID- 8144898
TI  - Sublytic complement attack exposes C-reactive protein binding sites on cell
      membranes.
AB  - C-reactive protein (CRP) is an acute phase serum protein synthesized by the
      liver. CRP has been localized to acute inflammatory sites and has been postulated
      to facilitate the removal of damaged cells. CRP binds to a number of ligands that
      may be present in inflammatory sites, and the extent to which individual ligands
      are involved in its binding to tissue sites is unknown. Complement activation is
      important in the tissue damage in many inflammatory conditions causing cell
      membrane damage and recruitment of inflammatory cells. This paper describes the
      binding of CRP to complement-damaged cell membranes. Raji cells activate the
      alternative complement pathway resulting in the deposition of C3b and membrane
      attack complexes (MAC) on the cell membrane. However, Raji cells are relatively
      resistant to killing by human complement. Treatment of Raji cells with human
      serum led to calcium-dependent phosphocholine-inhibitable CRP binding. CRP
      binding was eliminated by depletion of C3, C5, or C8 and reduced by depletion of
      C9 from serum. CRP binding preceded cell death and co-localized with MAC on cell
      membranes. CRP binding to complement-treated liposomes required
      phosphatidylcholine in addition to the MAC indicating that membrane phospholipids
      rather than the MAC proteins provide the binding sites for CRP. However, for both
      liposomes and Raji cells disruption of the lipid bilayer by complement attack was
      required for CRP binding to occur. These results support the hypothesis that CRP
      binding at sites of inflammation may be mediated by exposed phospholipids on
      damaged cell membranes.

PMID- 8144899
TI  - Secretion of IL-4 from human basophils. The relationship between IL-4 mRNA and
      protein in resting and stimulated basophils.
AB  - Purified human basophils have been examined for secretion of IL-4 protein and
      expression of IL-4 mRNA after stimulation with several secretagogues. In general,
      these studies used a 15-min preincubation with IL-3, before challenge with
      secretagogues. Under these conditions, IL-4 release averaged 30 pg/10(6)
      basophils (range 4-70) after challenge with anti-IgE Ab. FMLP and C5a led to
      somewhat lower levels of secretion. A direct comparison of basophils at 88 to 99%
      purity with basophils from the same preparations, but at lower purities, showed
      that the amount of IL-4 secretion was proportional to the purity of the
      basophils. The presence of mRNA for IL-4 (as determined by reverse transcriptase
      PCR, competitive reverse transcriptase-PCR, or Northern blots) was also strictly
      related to the purity of the basophils. IL-4 mRNA was also found to be
      constitutively present and was increased after stimulation. The concentration of
      polyclonal anti-IgE Ab required for optimal IL-4 release was somewhat less than
      that required for optimal histamine release. IL-4 secretion was slower (t1/2 of
      1.5 h) than histamine release and was inhibited by cycloheximide. In a final
      series of studies, we found that IL-3 was not required for IL-4 secretion; a
      short 15-min preincubation with IL-3 resulted in the same or slightly less IL-4
      release than no treatment with IL-3. In contrast, an 18-h pretreatment with IL-3
      resulted in a nearly tenfold increase in IL-4 secretion. We conclude that human
      basophils secrete IL-4 in response to several secretagogues and that IL-3 priming
      is not necessary to observe IL-4 secretion.

PMID- 8144900
TI  - Correlations among tyrosine phosphorylation of Shc, p72syk, PLC-gamma 1, and
      [Ca2+]i flux in Fc gamma RIIA signaling.
AB  - Tyrosine phosphorylation plays a critical role in Fc gamma RIIA signaling. In a
      mouse macrophage cell line transfected with human Fc gamma RIIA, cross-linking Fc
      gamma RIIA led to the transient generation of inositol 1, 4, 5-trisphosphate
      (IP3), [Ca2+]i flux, and rapid tyrosine phosphorylation of cellular substrates,
      including Shc, PLC-gamma 1, and a tyrosine kinase p72syk. In addition, tyrosine
      phosphorylated Fc gamma RIIA was co-precipitated with activated PLC-gamma 1. In
      contrast, no tyrosine phosphorylation of Shc or PLC-gamma 1 was detected in cells
      transfected with mutant receptors that failed to trigger [Ca2+]i flux. PMA
      inhibits both tyrosine phosphorylation of Shc and IP3 production leading to
      [Ca2+]i flux. However, PMA does not affect tyrosine phosphorylation of PLC-gamma
      1 and p72syk. These results suggest that tyrosine phosphorylation of Shc and PLC
      gamma 1 is important for the initiation of [Ca2+]i flux, and that activation of
      protein kinase C may modulate the activity of PLC-gamma 1 through
      serine/threonine phosphorylation.

PMID- 8144901
TI  - Endogenous norepinephrine regulates tumor necrosis factor-alpha production from
      macrophages in vitro.
AB  - Evidence for the extraneuronal accumulation of norepinephrine has been
      demonstrated to occur in macrophage (M phi), yet the physiologic role of this
      system remains undefined. We have assessed the response of murine peritoneal M
      phi to adrenergic antagonists. We have also defined a physiologic role of a M phi
      associated pool of the nonspecific adrenergic agonist norepinephrine. We
      investigated the constitutive involvement of alpha-adrenergic and beta-adrenergic
      receptors in LPS-induced TNF-alpha production. CFA-elicited M phis were incubated
      with LPS (1 microgram/ml) in the presence or absence of adrenergic agonists
      and/or antagonists. Although stimulation of alpha-adrenergic receptors increased
      TNF production and gene expression, beta-adrenergic receptors decreased it.
      Interestingly, when adrenergic antagonists along with LPS alone were added to M
      phi, they generated the response opposite to that produced by their suitable
      agonist, suggesting a role for endogenous norepinephrine in M phi. Thus, although
      alpha 2-adrenergic antagonists attenuated TNF production, beta-adrenergic
      antagonists augmented TNF expression in a concentration-dependent manner.
      Norepinephrine and epinephrine were found in M phi as determined by HPLC and LPS
      stimulation induced a significant decrease in their content. M phis were also
      incubated with LPS or medium only, washed, and then challenged 12 h later with
      LPS. When given a second LPS stimulation, M phis were found to have an increased
      response to alpha 2-adrenergic agonists and decreased response to alpha 2
      adrenergic antagonists. Therefore, M phi-associated norepinephrine appears to
      regulate LPS-induced TNF production in an autocrine fashion.

PMID- 8144902
TI  - Complement inhibitor of rat cell membrane resembling mouse Crry/p65.
AB  - Neuraminidase-treated rat erythrocytes are resistant to homologous rat C although
      they are readily hemolyzed by heterologous serum C via the alternative pathway.
      We established a mAb, mAb512, which allows for hemolysis of neuraminidase-treated
      rat erythrocytes by homologous rat serum. mAb512 detected rat erythrocyte
      membrane components with molecular masses of 65 kDa and 55 kDa by Western
      blotting analysis. Furthermore, mAb512 caused C3b deposition on rat myeloma cells
      after treatment with rat serum. 512Ag was purified by use of an immunosorbent
      column prepared with mAb512. Partial sequencing of 512Ag peptides showed
      significant homology to mouse Crry/p65 indicating that 512Ag could be the rat
      counterpart of mouse Crry/p65.

PMID- 8144903
TI  - Regulation of putrescine export in lipopolysaccharide or IFN-gamma-activated
      murine monocytic-leukemic RAW 264 cells.
AB  - The regulation of putrescine/polyamine export out of the cell was investigated
      during activation of monocytic-leukemic RAW 264 cells with LPS and IFN-gamma. The
      RAW 264 cells exported putrescine constitutively at a significant rate into the
      culture medium. This export process appeared to be selective for putrescine in
      that only a small amount of other polyamines (spermidine and N1-acetylspermidine)
      was found in the culture medium. LPS and IFN-gamma alone and in combination
      markedly stimulated putrescine export and nitrite production throughout a 24-h
      period. The efflux of putrescine but not nitrite was further increased by the
      addition of ornithine (the amino acid precursor of putrescine) to the culture
      medium. LPS and ornithine also stimulated the intracellular accumulation of
      putrescine in primary inflammatory macrophages and the export of putrescine into
      the peritoneal exudate of the mouse. A detailed comparison of the steady state
      rates of accumulation of intracellular putrescine/polyamines and the rate of
      putrescine efflux from the cells constitutively and after LPS, IFN-gamma, and
      ornithine indicated that a surprisingly large fraction of total polyamine
      biosynthesis is comprised of exported putrescine. The observed dose-dependent
      inhibition of putrescine export with the drug verapamil implicated the
      involvement of a specific membrane transport system sensitive to calcium influx
      in this process. The data are discussed in regard to the potential involvement of
      putrescine export in the regulation of intracellular polyamine levels, cell
      differentiation, and macrophage-mediated cytotoxicity.

PMID- 8144904
TI  - Mast cell and neutrophil expression of dog mast cell protease-3. A novel tryptase
      related serine protease.
AB  - In previous work the primary structure of a previously unknown protease was
      deduced from the sequence of a dog mastocytoma cDNA. The predicted preproprotein
      shares some features with mast cell tryptases but is no more than 49% identical
      in sequence to known trypsin-like enzymes, including dog tryptase. This study
      explores the expression of this protein, termed dog mast cell protease-3 (dMCP
      3). A polyclonal Ab was raised to a peptide corresponding to residues 166-181 of
      the deduced sequence. Anti-dMCP-3(166-181) Ig recognizes dMCP-3 expressed as a
      CheY fusion protein in Escherichia coli and binds to a approximately 36-kDa
      protein in extracts of dog mastocytomas. The Ab does not recognize dog tryptase,
      dMCP-3s closest known relative in mastocytoma cells. When used with fluorescein
      conjugated and alkaline phosphatase-conjugated secondary Abs, anti-dMCP-3(166
      181) Ig yields punctate cytoplasmic staining in mastocytoma cells, suggesting
      localization to intracellular granules. Staining is greatly reduced by
      preincubation with synthetic dMCP-3 peptide, supporting the specificity of the
      Ab. Immunohistochemical staining of normal dog tissues reveals scattered dMCP-3
      reactive cells in skin, intestine, trachea, and lung parenchyma. Double staining
      with Ab and methylene blue shows that anti-dMCP-3(166-188) Ig recognizes
      extravascular mononuclear tissue cells with metachromatic granules. In addition,
      cytoplasmic staining is seen in polymorphonuclear leukocytes within vessels in
      tissue sections and in leukocytes harvested from blood. Hybridization of dMCP-3
      cDNA to dog skin RNA provides further evidence of dMCP-3 gene transcription in
      normal tissue. Thus, this study provides immunochemical evidence of dMCP-3
      expression in dog mast cell tumors, normal tissue mast cells, and neutrophils.

PMID- 8144905
TI  - A novel subpopulation of primed T cells in the human fetus.
AB  - Virgin and memory T cells reciprocally express high levels of the RA or the RO
      isoforms of CD45, respectively. In an examination of T cell expression of these
      two CD45 isoforms during human development, the RO+RA- "memory" T cells were
      infrequent in the newborn blood and spleen, but comprised approximately half of
      the T cells in adult tissues. These anticipated findings probably reflect the
      immunologic naivete of the newborn. Surprisingly, however, RO+RA- T cells were
      relatively abundant in fetal spleen and in cord blood samples from premature
      births, comprising approximately 25% and 10% of the T cells in these tissues,
      respectively. This early peripheral wave of RO+RA- T cells was composed of
      polyclonal T cells in both the CD4 and CD8 subpopulations. The fetal RO+ cells of
      CD4+ phenotype frequently expressed the CD25-alpha chain subunits that
      characterize high affinity IL-2 receptors, and were able to proliferate in
      response to exogenous IL-2. In further contrast with their RO+ memory T cell
      counterparts in adults, the fetal T cells were unresponsive to mitogenic anti-CD2
      and anti-CD3 antibodies. We conclude that the data suggest an embryonic
      population of autoreactive T cell clones with anergic characteristics.

PMID- 8144906
TI  - Rapamycin-induced long-term allograft survival depends on persistence of
      alloantigen.
AB  - In this study the mechanism of rapamycin-induced long-term allograft tolerance
      was investigated in a rat model. We have demonstrated that the tolerance is
      strain specific, but is not organ specific. The tolerized rats failed to generate
      high levels of donor-specific cytotoxic Ab and cytotoxic cells in vivo. Removal
      of the alloantigen from the tolerized rats with or without concomitant thymectomy
      could break down the status of tolerance, and the rats regained the capability to
      reject the grafts and to develop specific cytotoxic Ab and cytotoxic cells. These
      results clearly indicate that the maintenance of the rapamycin-induced long-term
      tolerance to allografts depends on the persistence of alloantigens.
      Mechanistically, we have shown that the reduced IL-2 production and the reduced
      antigenicity of the graft in the tolerized rat contribute to, but are not solely
      responsile for, the tolerance. The results of adoptive transfer experiments
      suggest that regulatory cells or suppressive serum factors are not involved in
      the tolerance. The fact that the removal of the alloantigen in the thymectomized
      rat could reverse the tolerance, indicates that there is no clonal deletion. We
      propose that chronic desensitization due to prolonged engagement of TCR by
      persistent alloantigens is the major mechanism at the late stage of the rapamycin
      induced allograft tolerance.

PMID- 8144907
TI  - Requirement of donor-derived stromal cells in the bone marrow for successful
      allogeneic bone marrow transplantation. Complete prevention of recurrence of
      autoimmune diseases in MRL/MP-Ipr/Ipr mice by transplantation of bone marrow plus
      bones (stromal cells) from the same donor.
AB  - MRL/MP-Ipr/Ipr (MRL/Ipr) mice possess radioresistant (9.5 Gy) abnormal stem cells
      and show a recurrence of autoimmune diseases within 5 mo of conventional
      allogeneic bone marrow transplantation. We recently have found that the MHC
      preference exists between hemopoietic stem cells and stromal cells; when bones
      are engrafted, donor-derived stromal cells present in the engrafted bones can
      migrate into the recipient bone marrows, which are replaced with both donor
      derived stromal cells and hematopoietic cells. Based on these findings, we
      attempted to prevent the recurrence of autoimmune diseases in MRL/Ipr mice by the
      transplantation of both bone marrow cells and bone (as a source of stromal
      cells). MRL/Ipr mice were irradiated (8.5 Gy) and then reconstituted with C57BL/6
      bone marrow cells plus bone grafts. The mice survived more than 48 wk after this
      treatment. Immunohistologic studies revealed that the mice were completely free
      from both lymphadenopathy and autoimmune diseases such as lupus nephritis and
      rheumatoid arthritis. Sera from these mice showed normal levels of circulating
      immune complexes and rheumatoid factors. Normal functions of both T cells and B
      cells were noted. Abnormal T cells such as Thy-1+B220+ cells present in
      nontreated MRL/Ipr mice could not be seen in the thus-treated mice. In addition,
      to our surprise, spleen cells from treated mice showed completely normal in vitro
      primary anti-SRBC responses. These results indicate that stromal cells in
      allogeneic bone marrow transplantation play a crucial role not only in the
      prevention of graft failure but also in the successful cooperation among APCs, T
      cells, and B cells. Although MRL/Ipr mice are radiosensitive and usually die of
      interstitial pneumonia or fatty liver due to the side effects of radiation, it
      should be noted that this strategy allows a reduction in the radiation dose (9.5
      Gy-->8.5 Gy), and that these mice can survive more than 48 wk without showing any
      symptoms of autoimmune diseases.

PMID- 8144909
TI  - Major histocompatibility complex class II gene disruption prevents experimental
      autoimmune myasthenia gravis.
AB  - To analyze the impact of lack of MHC class II gene expression, and to demonstrate
      the direct genetic evidence for the involvement of the MHC class II gene product
      in the development of experimental autoimmune myasthenia gravis (EAMG), MHC class
      II gene-disrupted C57BL6 mutant (-/-) and EAMG-susceptible MHC class II wild-type
      C57BL6 mice (+/+) were evaluated for the clinical and immunopathologic
      manifestations of EAMG. The deficiency of MHC class II, and therefore, CD4+ T
      cells, completely prevented the C57BL6 MHC class II mutant (-/-) mice from
      mounting an autoimmune response to the nicotinic acetylcholine receptor. Further,
      the mutant (-/-) mice failed to show any immunopathologic and clinical
      manifestations of EAMG. The data unequivocally provide direct genetic evidence
      for the essential role of MHC class II molecules in the induction of EAMG, and
      rule out any pathogenic effector role for MHC class I-restricted CD8+ T cells,
      gamma delta TCR-bearing cells, or NK cells, which are intact in the MHC class II
      mutant mice in the induction of EAMG.

PMID- 8144908
TI  - Structure of the VH and VL segments of monoreactive and polyreactive IgA
      autoantibodies to DNA in patients with systemic lupus erythematosus.
AB  - Anti-DNA IgA autoantibodies play an important immunopathologic role in SLE
      patients. To analyze the cellular origin and the VH and VL structure of anti-DNA
      IgA autoantibodies, we generated five IgA1 mAbs to DNA using B lymphocytes from
      three SLE patients. Two mAbs bound to ssDNA only and one to both ssDNA and dsDNA
      (monoreactive antibodies). The remaining two mAbs bound to DNA (one to ssDNA and
      the other to both ssDNA and dsDNA) and to other self and foreign Ag (polyreactive
      antibodies). The IgA mAb relative avidity for DNA ranged from 7.5 x 10(-8) to 8.0
      x 10(-10) g/microliters. The anti-DNA IgA mAb used VH segments of the VHI(VI-3b),
      VHII (VH2-MC2), VHIII (WHG16G and VH26c), and VHIV (V71-2) families in
      conjunction with V kappa I, V kappa IIIb, or V lambda I segments. All IgA mAb VH
      segments were juxtaposed with JH4b segments. The heavy chain CDR3 sequences were
      divergent in composition and length. When compared with those of the closest
      reported germ line genes, the IgA mAb VH and VL gene sequences displayed a number
      of differences. That these differences represented somatic point mutations was
      formally proved in both the monoreactive IgA mAb 412.67.F1.3 and the polyreactive
      IgA mAb 412.66.F1 VH segments by differential PCR amplification and cloning and
      sequencing of genomic DNA from the mAb-producing cell lines and autologous
      polymorphonuclear cells. The sequences of the germ line genes that putatively
      gave rise to the mAb 412.67.F1.3 and mAb 412.66.F1 VH segments were identical
      with those of the WHG16G and VH26c genes, respectively. In not only the
      monoreactive mAb 412.67.F1.3 but also the polyreactive mAb 412.66.F1 and mAb
      448.9G.F1 VH segments, the higher concentration of replacement (R) mutations and
      the higher R:S (silent) mutation ratios in the complementarity-determining region
      (infinity; 19:0) than in the framework region (1.0) (p = 0.00001, chi 2 test)
      were highly consistent with selection by Ag. In the five IgA mAb VH and VL
      segments, the putative and verified somatic point mutations yielded 68 amino acid
      replacements, of which 38 were nonconserved. Twenty of these yielded positively
      charged or polar residues that play a major role in DNA binding, including seven
      Arg, five Lys, three Tyr, two Gln, two His, and a Thr. The conserved amino acid
      changes included seven Asn. These findings suggest that anti-DNA IgA
      autoantibodies use a broad selection of VH and VL genes and enhance their fit for
      Ag by undergoing somatic hypermutation and Ag selection.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8144910
TI  - Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with
      systemic lupus erythematosus.
AB  - Endogenously activated CD8+ cells contribute to the aberrant immune regulation
      that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers
      release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum
      sCD8 content, its correlation with disease activity, and the in vitro release of
      sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients,
      were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE
      patients. sCD8 correlated positively with the clinical index for disease activity
      (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p < 0.0001), and
      negatively with serum C3 levels (r = -0.5, p < 0.04). Freshly isolated SLE PBMCs
      had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in
      vitro (p < 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be
      modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas
      anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched
      cultures. Moreover, sCD8 release increased significantly in PBMC cultures
      enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased
      sCD8 to original levels, but not after glutaraldehyde fixation, nor in the
      presence of anti-HLA mAb. Further, lectin-induced IgG production and
      proliferation were reduced in the presence of sCD8, suggesting that the soluble
      CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of
      active SLE likely reflect pathogenic cell activation, serum CD8 content may be an
      additional serologic activity marker, and its study could provide insights into
      mechanisms of disease.

PMID- 8144911
TI  - Idiotypic intravaginal vaccination to protect against candidal vaginitis by
      secretory, yeast killer toxin-like anti-idiotypic antibodies.
AB  - The principles of idiotypic (Id) vaccination were used to immunize against
      vaginitis caused by Candida albicans, a widespread and sometimes intractable
      disease in women. To this aim, a murine mAb (KT4, IgG1) neutralizing in vitro the
      anti-Candida activity of a yeast killer toxin (YKT) was used as an Id vaccine to
      elicit Abs with toxin-like activity in a rat vaginitis model. Nonimmunized and
      isotype-matched, irrelevant mAb-immunized rats served as controls. An effective
      protection was obtained in Id-vaccinated animals, as demonstrated by a highly
      significant decrease in vaginal Candida CFU compared with controls. The
      protection was associated with rising vaginal titers of anti-idiotypic Abs
      (IdAb), prevalently of the IgA isotype, that were able to passively transfer the
      protective state to nonimmunized animals. The vaginal IdAb possessed YKT-like
      activity because they were able to kill in vitro the challenging fungal cells,
      and this killing was neutralized by the mAb KT4. Overall, these data demonstrate
      that secretory IdAb elicited by intravaginal Id vaccination with mAb KT4
      protected the rats from the infectious challenge with Candida albicans by
      molecular mimicking YKT activity as its internal image.

PMID- 8144912
TI  - Islet cell antigen 512 is a diabetes-specific islet autoantigen related to
      protein tyrosine phosphatases.
AB  - Islet cell Ag 512 (ICA512) is a recombinant human Ag that was isolated from an
      islet cDNA expression library by screening with human insulin-dependent diabetes
      mellitus sera. Specificity of reaction with diabetic sera was demonstrated
      initially by immunoprecipitation with a small number of diabetic and normal serum
      samples. To permit quantitative and rapid serum testing, ICA512 was purified and
      adapted to an ELISA format. In this way, a sensitivity of 48% with newly
      diagnosed diabetic sera has been measured with a panel of 80 sera. DNA sequencing
      of ICA512-3, a cDNA that contains a 1644 bp open reading frame, suggests that it
      codes for a transmembrane protein having a single membrane-spanning segment and a
      cytoplasmic domain that is closely related to the first intracellular (catalytic)
      domain of the T cell protein tyrosine phosphatase, CD45. Northern blot analysis
      of poly(A)+ RNAs from several human tissues indicates that ICA512 mRNA is
      expressed in brain and pancreas.

PMID- 8144913
TI  - Induction of circulating antagonists to IL-1 and TNF by IL-2 administration and
      their effects on IL-2 induced cytokine production in vitro.
AB  - The objectives of this study were to determine whether intensive immunotherapy
      with IL-2 results in detectable levels of circulating IL-1 and TNF antagonists
      and whether the levels achieved in vivo are sufficient to affect the generation
      of secondary proinflammatory cytokines such as IL-1 beta and TNF-alpha. We also
      sought to determine the extent to which endogenous TNF mediates the generation of
      an IL-1 antagonist by IL-2-activated PBMCs. In patients undergoing high dose IL-2
      immunotherapy, plasma IL-1 receptor antagonist (IL-1ra) levels rose dramatically
      after the first IL-2 injection, reaching a plateau of 11.03 +/- 0.92 ng/ml within
      4 h. TNF-soluble receptor p55 (TNFsRp55) was also detected in the plasma shortly
      after initiating treatment, and the levels progressively increased throughout the
      treatment course. PBMCs exposed to IL-2 expressed IL-1ra mRNA and secreted the IL
      1ra protein, but neither PBMCs nor neutrophils shed TNFsRp55 in response to IL-2
      or supernatants from IL-2-activated PBMCs. IL-1ra at concentrations achieved in
      the plasma during IL-2 immunotherapy (approximately 10 ng/ml) inhibited the in
      vitro production of IL-1 beta and TNF-alpha by IL-2-activated PBMCs by 65% and
      30%, respectively. Although the monomeric receptor TNFsRp55 at concentrations
      achieved in the plasma had no effect on the in vitro production of IL-1ra, TNF
      alpha, or IL-1 beta, the bivalent TNFsRp75-Fc chimera suppressed the generation
      of TNF and IL-1. IL-1ra synthesis was unaffected. These results suggest that the
      amount of IL-1ra generated in response to IL-2 is most likely sufficient to down
      modulate the production of proinflammatory cytokines.

PMID- 8144914
TI  - Unique C1 inhibitor dysfunction in a kindred without angioedema. I. A mutant C1
      INH that inhibits C1-s but not C1-r.
AB  - We have described hereditary incomplete deficiency of the fourth component of
      complement (C4) in 10 members of a large kindred. C4 deficiency in this kindred
      is not linked to C4 loci in the HLA region. C4 synthesis is decreased, and C4
      catabolism is normal in kindred members with low serum C4 levels. We have
      discovered a uniquely dysfunctional C1 inhibitor in all C4-deficient members of
      this kindred. C1 inhibitor dysfunction is revealed by incubating sera of affected
      members with EDTA, which destroys all C4 activity in these sera, but not in
      normal sera or sera from individuals with partial C4 deficiencies. The M(r) of C1
      inhibitor purified from affected members is normal, but approximately 50% of this
      C1 inhibitor resists cleavage by trypsin (0.14 microM) at arg444, suggesting a
      substitution at this position. Moderate increases in trypsin, however, result in
      cleavage of the resistant molecules, which would not be expected if arg444 were
      the site of the mutation. All molecules in C1 inhibitor purified from affected
      members' plasma bind to activated C1s (C1-s), but approximately 50% of molecules
      in these preparations do not bind to activated C1r (C1r). These findings show
      that affected kindred members have a unique mutation in C1 inhibitor. The mutant
      C1 inhibitor does not prevent the activation of C1s by C1-r when serum Ca2+ is
      chelated by EDTA, but its inhibition of C1-s is normal in vivo, as shown by
      normal C2 levels, normal C4 catabolism, and absence of angioedema in C4-deficient
      members. The nature of the mutation, its selective failure to inhibit C1-r, and
      its relationship to decreased C4 synthesis remain to be defined.

PMID- 8144915
TI  - Class I-restricted cytotoxic T lymphocytes are directly cytopathic for their
      target cells in vivo.
AB  - Although CD8-positive, class I-restricted CTL play a critical role in viral
      clearance and immunopathology in many model systems, they have not been shown to
      directly kill their target cells in vivo at the single cell level. Using a
      hepatitis B surface Ag transgenic mouse model of class I-restricted, CTL-mediated
      liver disease, we now demonstrate that CD8-positive, Ld-restricted hepatitis B
      surface Ag-specific CTL bind and kill their target cells in vivo by triggering
      them to undergo degenerative cytologic changes compatible with apoptosis.
      Unexpectedly, the data also indicate that the pathologic consequences of this
      direct, Ag-specific CTL effect are much less severe than the cytodestructive, Ag
      nonspecific inflammatory response that they induce when they are activated by Ag
      recognition.

PMID- 8144916
TI  - Role of bcl-2 and IL-5 in the regulation of anti-IgM-induced growth arrest and
      apoptosis in immature B cell lines. A cooperative regulation model for B cell
      clonal deletion.
AB  - Recent studies of transgenic mice have confirmed that clonal deletion is involved
      in the development of B cells. However, little is known about intercellular and
      intracellular molecular events regulating B cell clonal deletion. We investigated
      the role of bcl-2 and cytokines in the regulation of B cell clonal deletion using
      anti-IgM-induced growth arrest and apoptosis in immature B cell lines as a model.
      We show here that overexpression of Bcl-2 protein in stably transfected immature
      B cells partially inhibits anti-Ig M-induced apoptosis but does not affect growth
      arrest. Similarly, IL-5 has a strong inhibitory effect on anti-IgM-mediated
      apoptosis but has a weak inhibitory effect on growth arrest. Finally, although
      both bcl-2 overexpression and exogenous IL-5 cooperate with bacterial LPS to
      block apoptosis, bcl-2 overexpression and exogenous IL-5 have no additive
      inhibitory effect on anti-Ig induced apoptosis. These findings indicate that anti
      IgM-induced apoptosis is independently regulated from growth arrest and is
      controlled by at least two independent pathways: One is regulated by either Bcl-2
      protein or IL-5 and the other is regulated by LPS. Activation of both the bcl
      2/IL-5 and LPS pathways is necessary for complete inhibition of apoptosis, and
      presumably, clonal selection of the immature B cells.

PMID- 8144917
TI  - Role of dermal cells from normal and ultraviolet B-damaged skin in induction of
      contact hypersensitivity and tolerance.
AB  - With conventional regimens for induction of contact hypersensitivity with highly
      reactive haptens, circumstantial evidence implicates both epidermal and dermal
      APC. However, similar applications of hapten to skin that has been treated with
      an acute, low dose UVB radiation protocol induce contact hypersensitivity only in
      certain genetically defined strains of mice, termed UVB-resistant. Moreover, mice
      that fail to acquire contact hypersensitivity when hapten is painted on UVB
      exposed skin display hapten-specific tolerance. In the present study, dermal cell
      suspensions have been prepared from normal and UVB-exposed mouse skin as a means
      of identifying the cell(s) that: 1) provide APC function after UVB radiation in
      UVB-resistant mice; and 2) confer tolerance after UVB radiation in UVB
      susceptible mice. The results confirm that the normal murine dermis contains Ia+
      cells that, when hapten-derivatized in vitro and injected s.c. into naive,
      syngeneic mice, possess typical Ag-presenting function. Cells with similar
      function are retained in the dermis of UVB-resistant mice after exposure to UVB
      radiation, whereas dermal cells of UVB-exposed skin of UVB-susceptible mice
      display no ability to induce contact hypersensitivity. Instead, the latter dermal
      cells, when hapten-conjugated and injected s.c., induce tolerance. Thus, doses of
      UVB radiation that deplete the epidermis of Langerhans cells do not deplete the
      dermis of UVB-resistant mice of contact hypersensitivity-inducing APC, but do
      confer upon cells within the dermis of UVB-susceptible mice the capacity to
      induce unresponsiveness.

PMID- 8144918
TI  - Gene transfer studies of T cell receptor-gamma delta recognition. Specificity for
      staphylococcal enterotoxin A is conveyed by V gamma 9 alone.
AB  - gamma delta T cells bearing the V gamma 9 gene segment have been shown to
      recognize staphylococcal enterotoxin A (SEA) and a range of other Ags including
      mycobacterial Ags. We have established an experimental system to analyze the
      recognition properties of human TCR-gamma delta on a molecular level by
      transferring the receptor from its original T cell into a Jurkat T cell host that
      does not express an endogenous TCR. Three groups of transfectants that express
      the same delta-chain, V delta 1, but different gamma-chains (V gamma 9-J2-C gamma
      2, V gamma 3-J2-C gamma 2, and V gamma 9-JP-C gamma 1) together with the
      endogenous CD3 were obtained. The transfectant T cells each expressing different
      gamma delta receptors all produced IL-2 after stimulation with plastic bound anti
      CD3 Ab, but only those expressing V gamma 9 responded to stimulation with SEA in
      the presence of an autologous lymphoblastoid B cell line. In addition,
      transfectants that expressed V delta 2 combined with V gamma 9 could also respond
      to SEA. These results indicate that the V gamma 9 portion of the receptor,
      independent of the J region and C region or the delta-chain, is responsible for
      recognizing SEA.

PMID- 8144919
TI  - Soluble and membrane-bound TNF-alpha are involved in the cytotoxic activity of B
      cells from tumor-bearing mice against tumor targets.
AB  - Splenic B cells from BALB/c mice bearing mammary adenocarcinomas are capable of
      performing Ab-dependent cellular cytotoxicity. Effector-target conjugation after
      18 h results in minimal cytoplasmic damage, whereas extensive nuclear
      disintegration is observed. To determine whether splenic B cells from tumor
      bearing mice can effect direct cytotoxicity against tumor cells, L929 and WEHI
      164 cells were used as targets. B lymphocytes from tumor-bearing mice, but not
      from normal animals, were capable of lysing these two types of tumor cells.
      However, only a low level of cytotoxicity could be detected when the
      nontumorigenic 3T3 cells were used as targets. To elucidate the mechanism of
      cytotoxicity of these killer B cells, RNase protection assays were performed
      using perforin, granzyme A, TNF-alpha, and lymphotoxin probes. No perforin,
      granzyme A, or lymphotoxin RNA could be detected in purified preparations of B
      cells from normal and tumor-bearing mice. B cells from normal mice did not have
      TNF-alpha RNA. In contrast, B cells from tumor bearers expressed TNF-alpha RNA.
      TNF-alpha could be detected in supernatants from both unstimulated and stimulated
      tumor bearers' splenic B cells, as measured by ELISA, and its lytic activity was
      neutralized by anti-TNF-alpha Ab. Western blots revealed the presence of TNF
      alpha on the surface of the killer B cells. Paraformaldehyde-fixed B cells from
      tumor-bearing mice but not from normal animals were able to lyse TNF-alpha
      sensitive tumor targets. This cytotoxicity was neutralized by anti-TNF-alpha Ab.
      These results suggest that TNF-alpha in soluble and membrane-bound forms may be
      involved in the mechanism of cytotoxicity exerted by B cells from tumor-bearing
      mice.

PMID- 8144920
TI  - T cell-induced Ig allotypic suppression in mice. Basis for emergence or
      tolerization, during the perinatal period, of natural T cells specific to the
      IgG2ab allotype.
AB  - We have previously described an anti-IgG2ab T cell activity in normal Igha/a
      mice. Their congenic partner at the Igh locus (Ighb/b) and Igha/b hybrids bred
      from them, do not display this T cell activity but express IgG2ab. As these mice
      are supposed to possess the same genetic elements related to this potential T
      cell repertoire, only somatic selection mechanisms could be responsible for their
      different behavior. In this study, we investigated the basis for the emergence
      (in Igha/a mice) or tolerization (in Ighb/b-congenic mice and in Igha/b hybrids)
      of these natural anti-IgG2ab T cells. Stringent perinatal B cell deprivation in
      Ighb/b and Igha/b mice resulted in the emergence of anti-IgG2ab T cells, as these
      individuals could be subjected to autoimmune, T cell-mediated IgG2ab suppression.
      Furthermore, the acquisition of anti-IgG2ab T cell activity was drastically
      reduced in Igha/a mice, perinatally exposed to IgG2ab; thus, the presence of this
      allotype leads to tolerization of these specific T cells.

PMID- 8144921
TI  - Clustering of class I HLA molecules on the surfaces of activated and transformed
      human cells.
AB  - We surveyed cells for the clusters of class I HLA molecules, HLA-I, which we have
      previously found on JY lymphoblasts. Two fluorescence techniques, fluorescence
      resonance energy transfer and electron exchange quenching, detected clustered HLA
      I molecules on activated normal B and T cells, on cells of B and T lymphoblast
      lines, and on transformed fibroblasts. No HLA-I clusters were detectable in the
      surfaces of resting B or T cells or normal fibroblasts. HLA clustering correlates
      perfectly with the presence of the HC-10 epitope of beta 2-microglobulin (beta
      2m)-free heavy chains at the cell surface although not with the amount of this
      epitope expressed. Clustering was reversed by exogenous beta 2m, but this did not
      change the amount of HC-10 bound. This suggests that a form of beta 2m-free heavy
      chain in equilibrium with both native HLA molecules and fully denatured HC-10
      positive heavy chains is involved in HLA-I cluster formation.

PMID- 8144922
TI  - Mice deficient in CD23 reveal its modulatory role in IgE production but no role
      in T and B cell development.
AB  - To assess roles of CD23 in lymphocyte development and immune function in vivo,
      CD23-deficient mice (CD23-/-) were generated. Mice heterozygous with respect to
      the defective allele (CD23+/-) display 50% reduced levels of CD23 expression on
      CD23+ cell types. This pattern is consistent with a lack of parental or tissue
      specific imprinting of the CD23 gene. Neither a 50% reduced level nor a complete
      lack of CD23 caused profound changes in lymphocyte compartments (thymocytes,
      peripheral T cells, and B-1 and B-2 B cells). The lack of CD23 also did not
      significantly alter in vitro the proliferative response of B cells triggered via
      the Ag receptor in combination with CD40 ligand, IL-2, and/or IL-4. Effects on
      polyclonal Ig production were tested in a Th2 cell-driven immune response in vivo
      after infection with Nippostrongylus brasiliensis, a parasite that dramatically
      enhances CD23 expression on B cells. In both primary and secondary immune
      responses, heterozygous CD23+/- mice developed slightly higher and CD23-/- mice
      similar serum IgE and IgG1 levels as compared with CD23+/+ (wild-type) mice. The
      increase in blood eosinophil counts was similar in all three types of mice. These
      findings show that after N. brasiliensis infection 1) a complete lack of CD23 in
      vivo neither prohibits nor significantly alters quantitatively polyclonal IgE
      levels in serum, and 2) a 50% reduction in cell-surface CD23 expression (CD23+/-
      mice) correlates with slightly increased serum IgE levels.

PMID- 8144923
TI  - Cyclic AMP inhibits phosphatidylinositol-coupled and -uncoupled mitogenic signals
      in T lymphocytes. Evidence that cAMP alters PKC-induced transcription regulation
      of members of the jun and fos family of genes.
AB  - T lymphocyte stimulation via the Ag receptor results in activation of
      phospholipase C gamma 1 that catalyses the hydrolysis of phosphatidylinositol
      (PI). The hydrolysis generates inositol phosphate and diacylglycerol, which in
      turn, increase intracellular Ca2+ concentration and activates protein kinase C,
      respectively. Agonists operating via the adenylate cyclase pathway or cell
      permeable cAMP analogues inhibit T cell activation by interfering with the PI
      turnover. We have shown that dbcAMP inhibits PI-independent mitogenic signals in
      T cells after stimulation with TPA plus ionomycin. dbcAMP inhibited the TPA plus
      ionomycin-induced transcription of IL-2 and IL-2R genes in EL4 cells, suggesting
      interference with biochemic events downstream to PI hydrolysis and upstream to
      transcription of early activation genes. Because many of the early genes
      operating in T cell mitogenesis possess a TPA-response element (TRE) in their
      promoter region, we tested the effect of cAMP on the TRE-binding protein, TPA
      response element (TRE) in their promoter region, we tested the effect of cAMP on
      the TRE-binding protein, AP-1. dbcAMP increased the binding activity of nuclear
      proteins consisting of Fos:Jun heterodimers to a TRE-containing oligonucleotide,
      but altered the composition of Jun proteins in the AP-1. Furthermore, the TPA
      plus ionomycin-induced transcription program of members of the jun and fos family
      of genes was altered by dbcAMP, suggesting that inhibition of T cell
      proliferation by dbcAMP is a consequence of intervention in transcriptional
      regulation by TRE-binding proteins.

PMID- 8144924
TI  - Mechanism involved in the systemic suppression of antigen-presenting cell
      function by UV irradiation. Keratinocyte-derived IL-10 modulates antigen
      presenting cell function of splenic adherent cells.
AB  - Exposure to UV radiation suppresses tumor rejection and delayed-in-time
      hypersensitivity reactions and depresses splenic APC function. Because almost all
      of the UV radiation is absorbed in the upper layers of the skin, it appears
      unlikely the direct irradiation of APC can account for the impaired ability of
      splenic adherent cells to present Ag after total-body UV exposure. Because UV
      irradiated keratinocytes release IL-10, and in light of the well-documented
      effects of IL-10 on Ag presentation, we tested the hypothesis that keratinocyte
      derived IL-10 is responsible for the systemic impairment of APC function
      following UV exposure. Injecting supernatants from UV-irradiated keratinocytes
      suppressed the ability of splenic adherent cells to present Ag. Treating the
      supernatants with anti-IL-10 mAb neutralized the suppressive effect. Similarly,
      when splenic adherent cells were isolated from mice exposed to UV radiation, APC
      function was suppressed. Injecting the UV-irradiated animals with anti-IL-10
      restored APC function. In addition, spleen cells from UV-irradiated mice did not
      efficiently present Ag to Th1 clones, and injecting anti-IL-10 after UV exposure
      restored APC function. The reverse was observed when spleen cells from UV
      irradiated mice were used to present Ag to Th2 clones; in which case, UV exposure
      enhances APC function, and anti-IL-10 reverses this effect. These findings
      suggest that UV-induced, keratinocyte-derived IL-10 can modulate splenic APC
      function.

PMID- 8144925
TI  - Age- and microenvironment-associated influences by platelet-derived growth factor
      on T cell function.
AB  - Platelet-derived growth factor (PDGF) is produced by numerous cell types in
      response to a variety of activation signals. Although the role of PDGF in
      cellular proliferation is well established, the immunomodulatory effects of this
      peptide growth factor are only now being delineated. We previously established
      that PDGF alters the profile of lymphokines produced by activated T cells
      obtained from the peripheral lymph nodes of adult mice. We now report that T
      cells residing in lymphoid organs that receive their major afferent lymphatic
      drainage from gut mucosa are relatively resistant to the effects of this growth
      factor. As the vast majority of peripheral T cells are in the recirculating T
      cell pool, these findings suggest that tissue-specific microenvironmental factors
      function to regulate the sensitivity of T cells to PDGF-mediated influences.
      Additional studies have determined that the normal process of aging is
      accompanied by a systemic loss in T cell responsiveness to PDGF. Although the T
      cells of immature (2-wk-old) and young adult mice are responsive to the
      immunomodulatory influences of PDGF, T cells of aged animals (> 100 wk) are
      relatively resistant to its effects. Some of the immune abnormalities noted to
      occur during the aging process appear to represent a consequence of the
      dysregulated production of IL-6. We therefore evaluated whether IL-6 was
      responsible for modifying the sensitivity of T cells to PDGF. Data presented
      herein demonstrate that IL-6 abrogates the ability of PDGF to modify lymphokine
      production by T cells after activation. Therapeutic measures capable of reducing
      spontaneous IL-6 production in aged mice restored the ability of their T cells to
      respond to PDGF, suggesting that the dysregulated production of IL-6 within the
      aged host interferes with the ability of PDGF to convey important
      microenvironmental information to T cells residing in peripheral lymphoid organs.

PMID- 8144926
TI  - Switch circles from IL-4-directed epsilon class switching from human B
      lymphocytes. Evidence for direct, sequential, and multiple step sequential switch
      from mu to epsilon Ig heavy chain gene.
AB  - Ig isotype switch via deletional recombination is accompanied by excision of the
      intervening DNA between the two switch regions. The excised DNA is looped out as
      extrachromosomal circular DNA or switch circle. Such switch circles have been
      isolated and characterized in mice. We investigated deletional recombination in
      human B cells undergoing Ig isotype switching to demonstrate whether switch
      circles are also excised, and to thereby gain insight into the processes involved
      in human isotype switching. We characterized the deleted switch circular DNA from
      IL-4 directed mu to epsilon switching in polyclonal human B lymphocytes. By using
      two sets of specially designed PCR primers, we amplified switch circle fragments
      representing switch circles resulting from mu to epsilon direct switching and mu
      gamma-epsilon sequential switching. The PCR-amplified products were subcloned by
      a TA cloning strategy and resulting clones were screened by hybridization with a
      5'S epsilon probe. Sequence analysis of the positive clones revealed that all
      clones representing mu to epsilon direct switching indeed had 5'S epsilon
      directly joined to 3' S mu. Most clones representing mu-gamma-epsilon sequential
      switching showed 5'S epsilon joined to 3' S gamma as expected. However, two
      clones contained S mu and S alpha 1 sequences interposed between 5'S epsilon and
      3'S gamma, respectively. These data demonstrate that switch circles are excised
      during human B cell isotype switching, and that IL-4 directed epsilon class
      switching is accomplished by 1) direct mu to epsilon switching, 2) sequential mu
      gamma-epsilon switching, and 3) double sequential mu-alpha-gamma-epsilon
      switching.

PMID- 8144927
TI  - Recognition of a single amino acid change on the surface of a major
      transplantation antigen is in the context of self peptide.
AB  - The transcripts encoding two strongly alloantigenic class I mutant molecules,
      Kdm4 and Kdm5, were characterized and found to encode products that differ from
      the parental Kd glycoprotein by single amino acid substitutions. The Kdm4
      molecule has an amino acid change at position 114, an integral component of a
      beta-sheet associated with pockets D and E of the peptide binding site. The basis
      for strong alloantigenicity of the variant molecule can be attributed to
      differences in peptide binding that were visualized by HPLC analysis of eluted
      peptides. In contrast, the Kdm5 molecule differs from the parent at position 158,
      a component of the alpha-helix that is not associated with any of the pockets of
      the peptide binding site. No differences in peptide binding by Kdm5 in comparison
      with the parent Kd molecule were seen by HPLC, suggesting that the variant and
      parent molecules bind the same set of peptides. The ability of (dm4 x dm5) F1
      hybrid mice to recognize and lyse BALB/c stimulator cells indicates that the
      alloantigenic properties determined by the 158 substitution result from the
      interactions of the alpha-helix regions (changed in dm5) with the pockets of the
      binding site (changed in dm4). We conclude that self peptides shared by the F1
      hybrid and the BALB/c stimulator cells are recognized in the context of
      structural features of the helices of the Ag-presenting molecule as alloantigenic
      determinants.

PMID- 8144928
TI  - Regulation of the murine Fc epsilon RII (CD23) gene. Functional characterization
      of an IL-4 enhancer element.
AB  - The murine B cell IgE receptor (Fc epsilon RII, CD23) has been implicated in
      various functions including IgE regulation, Ag presentation, and B cell
      differentiation/activation. We have undertaken a series of studies to identify
      promoter sequences that are important for the constitutive and IL-4-induced
      expression of the murine Fc epsilon RII in M12.4.5 B lymphoma cells. By use of
      RNase protection analysis it was established that murine splenic B cells and
      M12.4.5 cells predominantly express the Fc epsilon RIIa form and that this
      receptor subtype accounts for the vast majority of IL-4-induced Fc epsilon RII
      mRNA in B cells. A 101-bp segment of the murine Fc epsilon RII proximal promoter
      coupled to a heterologous SV40 promoter was found to impart IL-4 inducibility in
      reporter assays. Removal of either 10 bp from the 5' end or 17 bp from the 3' end
      of this 101-bp fragment substantially reduced the IL-4 response. Both of these
      terminal deletions removed sequences that share homology with established IL-4
      response elements of MHC class II and Ig (gamma 1 and epsilon) heavy chain genes.
      In addition, near the center of this 101-bp fragment lies a sequence that is
      highly homologous with NF-kappa B/LPS response elements previously identified
      upstream of the A alpha gene. DNA fragments containing this sequence together
      with one of the putative IL-4 response elements were able to impart a small
      LPS/IL-4 response in M12.4.5 cells. These results suggest that IL-4 and LPS
      induction of murine B cell Fc epsilon RII expression is mediated by a complex of
      transcription factors.

PMID- 8144929
TI  - Regulation of antibody specificity to Plasmodium falciparum merozoite surface
      protein-1 by adjuvant and MHC haplotype.
AB  - An effective malaria vaccine must be capable of eliciting a protective immune
      response in individuals of diverse genetic makeup. In this report, we describe
      the co-regulation of immune responsiveness to growth-inhibitory Plasmodium
      falciparum merozoite surface protein-1 (MSP-1) epitopes by MHC-linked immune
      response genes and by the adjuvant used in MSP-1 vaccine formulations. When
      congenic mice differing in MHC haplotype were immunized with MSP-1 either in CFA
      or incorporated into a synthetic monophosphoryl lipid A (LA-15-PH)-liposome
      formulation, mice of different haplotypes produced anti-MSP-1 Abs capable of
      inhibiting P. falciparum growth. Mice of H-2b and H-2ja haplotypes produced Abs
      possessing high levels of inhibitory activity upon immunization with MSP-1 in LA
      15-PH/liposomes whereas these haplotypes produced noninhibitory Abs when
      immunized with MSP-1 in CFA. Conversely, H-2d haplotype mice produced inhibitory
      Abs when immunized with MSP-1 in CFA but not when immunized with MSP-1 in LA-15
      PH/liposomes. The LA-15-PH/liposome adjuvant was more effective than CFA in
      inducing growth-inhibitory Abs. The level of parasite growth inhibition observed
      for a particular mouse strain correlated with Ab titers against conserved, C
      terminal MSP-1 epitopes, which appear to be important targets for Ab-mediated
      inhibition in mice immunized with both adjuvant formulations. Our results suggest
      that adjuvant formulation and MHC genes act in a reciprocal manner to control
      immune responsiveness to specific epitopes, and raise the possibility of
      manipulating genetically-controlled responsiveness to vaccine Ags by utilizing
      alternative adjuvants in vaccine formulations.

PMID- 8144930
TI  - Role of CD8+ T cells in host resistance to systemic infection with Histoplasma
      capsulatum in mice.
AB  - Histoplasma capsulatum is a facultative intracellular fungus that spreads
      lymphohematogenously to involve organ systems rich in mononuclear phagocytes. We
      explored herein the in vivo effect of anti-CD8 rat mAb on the course of murine
      disseminated histoplasmosis. Treatment with anti-CD8 mAb caused a selective
      depletion of CD8+ T cells in naive mice infected with H. capsulatum. The loss of
      CD8+ T cells was associated with an increased number of H. capsulatum CFU in
      spleens and livers of mice during the first 3 wk of infection. Transgenic beta 2
      microglobulin-deficient mice (beta 2 M-/-) that lack MHC class I Ag and CD8+ T
      cells or heterozygous littermates were injected with H. capsulatum. At wk 1 of
      infection, the number of CFU in livers and spleens of beta 2 M-/- mice was
      similar to that of littermates. At wk 2 and 3, however, the fungal burden in
      spleens and livers of beta 2 M-/- mice was larger than that of heterozygous
      littermates. H. capsulatum-immunized mice given anti-CD8 mAb manifested impaired
      clearance of H. capsulatum upon rechallenge with a large inoculum of yeasts when
      compared to immunized controls. Histopathologically, the inflammatory response in
      spleens and livers of CD8+ T cell-depleted mice was similar to that of mice given
      control Ab. The results indicate that CD8+ T cells are necessary for optimal
      clearance of the fungus from tissues of mice infected with H. capsulatum.

PMID- 8144932
TI  - Cooperation between staphylococcal enterotoxin B and low dose melphalan in the
      cure of mice bearing a large MOPC-315 tumor and extensive metastases.
AB  - We have recently demonstrated the importance of V beta 8+/CD8+ cells for the
      curative effectiveness of a suboptimal low dose (0.75 mg/kg) of melphalan (L
      phenylalanine mustard; L-PAM) for mice bearing a large s.c. MOPC-315 tumor and
      extensive metastases. Here we show that staphylococcal enterotoxin B (SEB), which
      is known to selectively stimulate T cells expressing members of the TCR-V beta 8
      gene family, substantially improved the curative effectiveness of the suboptimal
      dose of L-PAM for mice bearing a large MOPC-315 tumor. Moreover, treatment of
      mice with mAb F23.1 (anti-V beta 8) abrogated the in vivo therapeutic effect of
      SEB for low dose L-PAM-treated MOPC-315 tumor bearers (L-PAM TuB mice). Analysis
      of the effect of SEB on the tumor-infiltrating lymphocytes (TILs) demonstrated
      that the SEB-mediated therapeutic effect was associated with a significant
      increase in: 1) the percentage of V beta 8+ cells among the CD8+ T cells that
      accumulated in the s.c. tumor nodules, 2) the total number of V beta 8+/CD8+
      cells present per tumor on day 4 after low dose L-PAM therapy, and 3) the ability
      of the TILs to lyse MOPC-315 tumor cells in vitro in a short term assay.
      Furthermore, treatment of mice with mAb F23.1 abolished the ability of SEB to
      render the TIL population of L-PAM TuB mice more cytotoxic in vitro for MOPC-315
      tumor cells. Thus, the SEB-mediated improvement in the therapeutic outcome of low
      dose L-PAM therapy for mice bearing a large MOPC-315 tumor may be due in part to
      SEB-mediated increase in the contribution of the V beta 8+ T cells to tumor
      eradication through enhancement in the magnitude of the anti-MOPC-315 lytic
      activity exhibited by the TIL population.

PMID- 8144931
TI  - Treatment of established lung metastases with tumor-infiltrating lymphocytes
      derived from a poorly immunogenic tumor engineered to secrete human TNF-alpha.
AB  - The growth of a poorly immunogenic methylcholanthrene (MCA)-induced murine (m)
      sarcoma genetically engineered to secrete human (h) TNF-alpha (MCA-102-hTNF) was
      studied. MCA-102-hTNF tumor cells were implanted in animals bearing three- or 7
      day pulmonary metastases established with the parental line MCA-102-WT (wild
      type). This model approximates the clinical situation in which patients with
      metastatic cancer would be vaccinated with autologous tumor genetically modified
      to stimulate the host immune response. Reduction in the number of pulmonary
      metastases was occasionally seen but was not consistently reproducible. Other
      cytokine-producing tumors had either no effect on distant pulmonary metastases
      (mIL-4, IFN-gamma) or a mild, inconclusive effect similar to hTNF-alpha (mTNF
      alpha). Significant growth inhibition of MCA-102-hTNF was noted in animals
      bearing pulmonary metastases. This inhibition was: 1) tumor specific (regression
      occurred only in animals bearing pulmonary metastases from the same parental
      line), 2) TNF specific (it was inhibited by in vivo administration of anti hTNF
      mAbs), 3) dependent on cellular immunity (immune-depletion with anti-CD4 or CD8
      mAbs permitted growth). Tumor-infiltrating lymphocytes (TIL) could not be grown
      from MCA-102-WT or MCA-102-hTNF tumors nor from MCA-102-WT subcutaneous implants
      in mice bearing MCA-102-WT pulmonary metastases. However, TIL could be grown from
      hTNF-secreting tumors implanted in mice bearing MCA-102-WT metastases. These TIL
      were therapeutic against established lung metastases from the parental tumor in
      adoptive immunotherapy models. These studies suggest a strategy for using gene
      modified tumors for the therapy of established cancer.

PMID- 8144933
TI  - Biochemical and biologic characterization of murine monocyte chemoattractant
      protein-1. Identification of two functional domains.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine-beta (or
      C-C) family of cytokines. Murine MCP-1, first identified as the JE gene, differs
      from human MCP-1 in molecular size and extent of glycosylation. We have used
      Chinese hamster ovary cells to express recombinant murine MCP-1 and find that its
      predominant form is a microheterogeneous protein of M(r) approximately 25,000.
      Most of MCP-1's microheterogeneity is due to variable amounts of sialic acid that
      are terminally attached to a constant number of O-linked oligosaccharide chains
      per molecule. This carbohydrate, along with a small amount of N-linked
      carbohydrate, accounts for 50% of the apparent molecular size of murine MCP-1 and
      is not required for in vitro monocyte chemoattractant activity. Mutational
      analysis shows that most of the carbohydrate is added to a 49-amino acid C
      terminal domain that is not present in human MCP-1 and is not required for in
      vitro biologic activity, suggesting that murine MCP-1 consists of an N-terminal
      domain containing monocyte chemoattractant activity and a heavily glycosylated C
      terminal domain of as yet unknown function. MCP-1 produced in COS cells contains
      a small amount of sulfate, but Chinese hamster ovary-produced MCP-1 does not. The
      absence of sulfate does not alter MCP-1's in vitro chemoattractant properties. In
      vitro, highly purified murine MCP-1 attracts monocytes, but not neutrophils, with
      a specific activity similar to human MCP-1 (EC50 approximately 0.5 nM).
      Equilibrium binding experiments with human monocytes reveal the presence of
      approximately 3000 binding sites per cell with a Kd of 0.77 nM. In vivo,
      injection of up to 1 micrograms murine MCP-1 in a variety of murine strains
      induces the appearance of a sparse mixed inflammatory infiltrate. The disparity
      between MCP-1's in vitro and in vivo effects suggests that other factors may be
      required to elicit a full-blown monocyte chemotactic response to MCP-1 in vivo.

PMID- 8144934
TI  - TNF induces internalization of the p60 receptor and shedding of the p80 receptor.
AB  - As is true for other peptide hormones, TNF causes the down-modulation of its own
      receptor. The process by which down-regulation occurs and the particular role of
      each of two recently identified receptors, however, are not understood. In this
      report we used Abs specific to p60 and p80 TNFR types to examine the ligand
      induced down-regulation in histiocytic cell line U-937. These cells express both
      types of TNFRs, but the amount of p80 is two to three times greater than that of
      the p60 receptor. Treatment of U-937 cells with the ligand led to maximum down
      modulation of TNFR within 30 min, and this decrease was found to be a result of
      receptor number and not affinity. When examined for the receptor type,
      approximately 90% of the p60 receptor and 35% of the p80 receptor was down
      regulated by the cytokine. Rapid internalization of TNF in U-937 cells is
      mediated through p60, because this process was inhibited only by anti-p60 Ab and
      was also inhibited in cells (PMA-pretreated) that primarily express the p80
      receptor. In contrast to p60, we observed that the ligand-induced shedding of the
      p80 receptor into the medium results in the down-regulation. Interestingly,
      however, the signal for shedding of the p80 receptor appears to be mediated
      through the p60 receptor, because anti-p60 Ab inhibited the shedding. Overall,
      our results provide evidence that ligand-induced down-modulation of TNFR is a
      result of the internalization of p60 and of the shedding of the p80 receptor and
      that the signaling for both is mediated through the p60 receptor.

PMID- 8144935
TI  - Regulation of neutrophil-derived chemokine expression by IL-10.
AB  - In this study, we examined IL-10 regulation of polymorphonuclear leukocyte (PMN)
      derived chemokine expression. Studies demonstrated that IL-10 dose dependently
      suppressed the expression and production of PMN-derived macrophage inflammatory
      protein-1 alpha (MIP-1 alpha), MIP-1 beta, IL-8 mRNA, and protein. Although
      inhibition of protein synthesis was found to superinduce the expression of PMN
      derived chemokine steady-state mRNA, the inhibitory activity of IL-10 was
      completely abrogated in the presence of either cycloheximide or puromycin. These
      data suggest that the effect of IL-10 on PMN-derived chemokine expression was
      through the production of de novo repressor protein(s). Next, we examined the
      half-life (t1/2) of chemokine mRNA by LPS-treated PMNs in the presence or absence
      of IL-10. The t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated
      for 4 h with LPS before actinomycin-D (Ac-D) addition were approximately 40 min,
      1.7 h, and 2 h, respectively, whereas the t1/2 from PMNs stimulated for 8 h
      before Ac-D were 2, 2, and > 9 h, respectively. Interestingly, IL-10
      significantly accelerated the decay of all three of the above chemokine mRNA. The
      t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated with LPS plus IL
      10 compared with LPS alone was reduced by 62, 50, and 40%, respectively, at the 4
      h time point and by 50, 25, and 70%, respectively, at the 8-h time point. These
      findings support the notion that PMNs are an important cellular source of both C
      X-C and C-C chemokines, and that IL-10 regulates both inflammatory/immune
      responses by not only modulating the activities of T cell, B cell, and
      mononuclear phagocyte function, but also by inhibiting PMN-derived chemokine
      expression.

PMID- 8144936
TI  - Involvement of the cystine transport system xc- in the macrophage-induced
      glutamate-dependent cytotoxicity to neurons.
AB  - Macrophages have been found to release glutamate and thereby induce neuronal cell
      death by excitotoxicity, a mechanism that seems to be operative in various
      neurologic diseases. In this study, it is shown that the presence of both cystine
      and glutamine in the culture medium is indispensable for brain macrophages to
      release glutamate and to cause neuronal cell death. Furthermore, release of
      glutamate requires protein synthesis since cycloheximide prevented accumulation
      of the neurotoxic molecule in supernatants of microglial cell cultures.
      Aminoadipate, which was shown to inhibit the uptake of cystine by system xc- in
      fibroblasts, efficiently reduced the release of glutamate. The requirement of
      glutamine and cystine for the release of glutamate by microglial cells as well as
      the inhibitory effect observed with aminoadipate shows the transport system xc-
      to be essential for the release of the excitotoxin glutamate by microglial cells.
      Phagocytosis of zymosan particles and stimulation with different bacterial
      components, such as LPS, protein A, tuberculin, and Staphylococcus enterotoxin A
      increased glutamate release two- to threefold above basal values. In addition,
      the effect of bacterial components was mimicked by TNF-alpha, but not by IL-1 and
      IL-6. Cytokines known to deactivate macrophages, such as TGF-beta, IL-4, and IL
      10, did not affect the transport system xc- in microglial cells. However,
      dexamethasone suppressed the glutamate release up to 50%.

PMID- 8144937
TI  - Receptors and transduction pathways for monocyte chemotactic protein-2 and
      monocyte chemotactic protein-3. Similarities and differences with MCP-1.
AB  - MCP-2 and MCP-3 are recently identified members of the Cys-Cys chemokine family
      with high sequence similarity with MCP-1 (62% and 71%, respectively). The present
      study was aimed at defining receptor usage and signal transduction pathways of
      MCP-2 and MCP-3 in human monocytes in comparison with MCP-1. MCP-2 and MCP-3
      induced migration of monocytes with a typical bell-shaped curve and maximal
      response at 10 and 50 ng/ml, respectively. The maximal response elicited by MCP-2
      and MCP-3 was lower (approximately 60%) than that of MCP-1. Pertussis toxin
      (PTox) inhibited the chemotactic activity of MCP-3 and MCP-1 (IC50 = 6.2 and 4.4
      ng/ml, respectively), whereas cholera toxin (CTox) had little effect on these two
      chemokines (IC50 > 1000 ng/ml). In contrast, MCP-2-induced chemotaxis was blocked
      by CTox (IC50 = 75 ng/ml) and relatively unaffected by PTox. MCP-3 and MCP-1
      induced a rapid increase in intracellular Ca2+ concentration, whereas MCP-2, in
      the range of concentrations active on chemotaxis, did not. MCP-1-, MCP-2-, and
      MCP-3-induced chemotactic responses were blocked by C-I, a serine/threonine
      kinase inhibitor, and by genistein, a tyrosine kinase inhibitor, with the MCP-2
      response being more sensitive than those induced by MCP-1 and MCP-3. MCP-1 and
      MCP-3 rapidly induced arachidonic acid release whereas MCP-2 was ineffective. MCP
      1 and MCP-3 cross-desensitized with each other in terms of Ca2+ transients and
      displaced with a comparable efficiency labeled MCP-1 from human monocytes. On the
      other hand, MCP-2 did not cross-desensitize with MCP-1 and MCP-3 and only
      partially (20%) displaced labeled MCP-1. Thus, in spite of high sequence
      similarity, MCP-2 differed considerably from MCP-1 and MCP-3 in terms of
      sensitivity to CTox and PTox, arachidonate and calcium mobilization, and capacity
      to compete for labeled MCP-1.

PMID- 8144938
TI  - Induction of IL-8 gene expression in human polymorphonuclear neutrophils by
      recombinant IL-2.
AB  - Induction of IL-8 gene expression was investigated in IL-2-stimulated circulating
      peripheral blood polymorphonuclear neutrophils (PMN). Brief exposure of normal
      PMN to human rIL-2 enhanced both transcriptional and translational expression of
      IL-8. The IL-8 mRNA was first detectable by 3 h, followed by a continuous
      maintenance of high mRNA levels up to 18 h. Maximal transcription was obtained
      with 1000 U/ml of IL-2, which achieved the level observed with known neutrophil
      activating factors such as granulocyte macrophage-CSF and Candida albicans. The
      protein synthesis inhibitor, cycloheximide, had no detectable effect on levels of
      IL-8 mRNA expression in PMN incubated in medium alone; however, cycloheximide
      could selectively modulate IL-8 mRNA transcription in PMN, depending on the
      cytokine used. Cycloheximide did not affect or alter IL-8 mRNA induction in IL-2
      treated PMN but abrogated it in granulocyte macrophage-CSF-treated PMN and super
      induced the level of IL-8 mRNA in C. albicans-treated PMN. Of significance was
      the observation that IL-2 has no direct chemotactic effect on PMN, whereas the
      cell-free supernatants from IL-2-stimulated PMN show potent chemotaxis for
      freshly isolated PMN, which can be specifically blocked by anti-IL-8 Abs. These
      findings suggested that the induction of IL-8 gene expression in PMN by IL-2 may
      be involved in the recruitment of PMN into tissues during local IL-2 therapy in
      human cancer and in part contribute to tumor rejection.

PMID- 8144939
TI  - Regulatory mechanisms for the expression of type IV collagenases/gelatinases in
      murine macrophages.
AB  - The purpose of this study was to determine the regulation of type IV collagenase
      expression in murine peritoneal macrophages (PEM) after they are incubated with
      LPS. LPS stimulated the production of the latent forms of 92-kDa (MMP-9) and 72
      kDa (MMP-2) type IV gelatinases in a dose-dependent (> 10 ng/ml) and serum
      dependent manner. Time course analyses revealed that LPS regulated the expression
      of MMP-9 and MMP-2 via discordant kinetics. Prolonged treatment of PEM with LPS
      decreased MMP-9 but not MMP-2 activities. IFN-gamma decreased the production of
      both gelatinases by PEM responding to LPS. TGF-beta stimulated production of both
      matrix metalloproteinases but blocked the LPS-mediated secretion of MMP-9. LPS
      stimulated MMP-9 production was suppressed by genistein and tyrphostin, two
      specific tyrosine kinase inhibitors, as well as H-7, a serine/threonine protein
      kinase inhibitor, but not by HA1004, a relatively selective inhibitor for PKA and
      PKG. Our data demonstrate that the secretion of MMP-2 and MMP-9 by murine PEM is
      differentially regulated, suggesting a distinct in vivo role for these two
      otherwise analogous type IV gelatinases in macrophage-mediated connective tissue
      destruction at sites of immunologic challenges.

PMID- 8144940
TI  - Recombinant and native zymogen forms of human complement factor D.
AB  - We have expressed a full-length cDNA clone encoding human factor D by using a
      baculovirus expression system. The purified recombinant protein reacted with Ab
      against native factor D, but was hemolytically inactive and slightly larger than
      factor D. These results suggested that the recombinant protein was the elusive
      zymogen of factor D. Amino acid sequencing demonstrated that the recombinant
      factor D consisted of two proenzyme forms with respective activation peptides,
      AAPPRGR and APPRGR. Catalytic amounts of trypsin converted recombinant profactor
      D to its enzymatically active form, exhibiting SDS-PAGE mobility and specific
      hemolytic activity similar to those of native factor D. About 90% of trypsin
      activated recombinant profactor D had the same NH2-terminus as factor D. Human
      thrombin, kallikrein, and plasmin could also activate recombinant profactor D,
      but relatively high concentrations of these enzymes were required and the
      specific hemolytic activity of the "activated" profactor D was about one-third
      that of native factor D. Trypsin-activatable profactor D was also purified from
      the urine of a patient with Fanconi's syndrome. This native profactor D
      represented less than 1.0% of the total antigenic factor D in the patient's urine
      and had a Gly-Arg dipeptide as the activation peptide. Apparently, urine
      profactor D was produced by cleavage of pre-profactor D at Arg-(-3) by a serine
      protease with trypsin-like specificity, which probably is different from the
      putative leader peptidase that produces the recombinant profactor D. Urine
      profactor D was inhibited by diisopropyl fluorophosphate although the recombinant
      proenzyme was resistant to this inhibitor.

PMID- 8144941
TI  - Differential mycobacterial 65-kDa heat shock protein T cell epitope recognition
      after adjuvant arthritis-inducing or protective immunization protocols.
AB  - Immunization of Lewis rats with heat-killed Mycobacterium tuberculosis (Mt) in
      mineral oil induces adjuvant arthritis (AA), associated with T cell responses to
      residues 180-188 of the mycobacterial 65-kDa heat shock protein (hsp65).
      Preimmunization with hsp65 protects rats against AA and other forms of arthritis.
      Several explanations for these protective effects have been proposed, including
      enhanced responsiveness to protective epitopes in hsp65, down-regulation of T
      cell responses to the 180-188 epitope, and activation of self-hsp60-reactive T
      cells. To assess the potential of these hypotheses, we analyzed hsp65 T cell
      epitopes recognized after immunization of Lewis rats with Mt or hsp65. Here we
      identify nine RT1.B1-restricted T cell epitopes in hsp65. Mt immunization induced
      T cell responses in which the 180-188 epitope was dominant, whereas hsp65
      immunization resulted in a co-dominance of this and two further epitopes, 216-225
      and 226-235. Two minor epitopes were recognized after hsp65 but not Mt
      immunization. These results indicate that hsp65 preimmunization does not down
      regulate responses to the AA-associated epitope, but does enhance responses to
      several hsp65 epitopes that are minor or absent after the AA-inducing
      immunization protocol. Cross-reactive T cell recognition of hsp65 and rat hsp60
      was limited to a single epitope (256-265), recognized after hsp65 immunization,
      but poorly recognized after Mt immunization. This study provides the necessary
      basis for elucidating the T cell events involved in the protective effects of
      hsp65 preimmunization.

PMID- 8144942
TI  - In vivo or in vitro anti-CD3 epsilon chain monoclonal antibody therapy for the
      prevention of lethal murine graft-versus-host disease across the major
      histocompatibility barrier in mice.
AB  - We explored the use of a single in vivo dose of an anti-CD3 epsilon mAb for graft
      vs-host disease (GVHD) prevention in mice. Anti-CD3 epsilon (145-2C11) given on
      the day of bone marrow (BM) transplant was highly effective in preventing GVHD in
      a dose-dependent manner. However, mice experienced acute toxicity as measured by
      early post-BM transplantation mortality, severe weight loss, and cachexia, which
      is likely due to T cell-dependent lymphokine production. Donor T cells were
      partly responsible because toxicity still occurred in mice injected with an
      allelic specific anti-CD3 epsilon mAb that only reacted with the donor strain.
      Toxicity was also dependent on the number of radioresistant host T cells present
      at the time of transplant, because toxicity still occurred when recipients were
      depleted of mature T cells in vivo with anti-CD4+ anti-CD8 mAbs, and were given T
      cell-depleted BM from SCID mice. Toxicity was eliminated by treating BM with anti
      CD3 epsilon mAb in vitro before BM transplant instead of administering the mAb in
      vivo. However, GVHD protection was not complete. Direct comparison of the in vivo
      and in vitro approaches revealed that the in vivo administration of anti-CD3
      epsilon mAb was more effective for GVHD protection and that a combination of the
      approaches was not beneficial. Flow cytometry studies were performed to assess
      the degree of CD3 epsilon chain modulation and T cell depletion obtained with in
      vitro vs in vivo anti-CD3 epsilon chain mAb. In mice given syngeneic BM
      transplants to avoid the confounding effects of GVHD, we found that in vivo anti
      CD3 epsilon mAb administration induced a more prolonged period of CD3 epsilon
      chain modulation and/or T cell depletion than either the in vitro approach or a
      third approach that involved anti-CD3 epsilon F(ab')2 fragments administered in
      vivo. These data indicate that targeting the Ag-specific TCR, especially in such
      a way as to avoid toxicity associated with T cell activation, may provide an
      important key for developing future GVHD therapies.

PMID- 8144943
TI  - Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus
      erythematosus.
AB  - SLE is a disease characterized by the generation of an immune response to intact
      nuclear Ags, especially components of the nucleosome, histones and DNA. The
      process of programmed cell death, or apoptosis, is characterized by cleavage of
      chromatin into oligonucleosomes and release of these nucleosomes into the
      extracellular space. To address the question of whether altered apoptosis might
      provide a source of extracellular nuclear Ags in SLE, we have examined apoptosis
      of lymphocytes isolated from patients with SLE, patients with rheumatoid
      arthritis (RA), and normal controls. Apoptosis was measured by three independent
      methods and confirmed by gel electrophoresis. Freshly isolated lymphocytes (t0)
      showed low levels of apoptosis. However, lymphocytes from SLE patients
      demonstrated a significant increase in the number of apoptotic cells at t0
      compared with normal controls and RA patients. In tissue culture, lymphocytes
      from all patient groups underwent apoptosis, but the rate of apoptosis of
      lymphocytes derived from SLE patients was 2.35-fold faster than apoptosis of
      lymphocytes from normal controls or RA patients. The increased rate of apoptosis
      could not be accounted for by corticosteroid or cytotoxic medication. There was a
      significant correlation between SLE disease activity as measured by the systemic
      lupus activity measure and rate of apoptosis in vitro. The release of intact
      nucleosomes during apoptosis was measured by ELISA; lymphocytes from SLE patients
      released increased amounts of nucleosomal material into the extracellular space
      in direct proportion to the rate of apoptosis. Abnormal apoptosis of lymphocytes
      in SLE may provide a source of extracellular nuclear Ag to drive the immune
      response and to allow the formation of immune complexes. The demonstration of
      altered in vitro apoptosis of lymphocytes derived from SLE patients raises the
      possibility that abnormalities of apoptosis may contribute to the pathogenesis of
      SLE.

PMID- 8144944
TI  - A chimeric protein comprised of IL-4 and Pseudomonas exotoxin is cytotoxic for
      activated human lymphocytes.
AB  - IL4-Pseudomonas exotoxin (IL4-PE4E) is a chimeric molecule in which human IL-4 is
      genetically fused to the mutated binding domain of Pseudomonas exotoxin. This
      molecule binds specifically to human IL-4 receptor-bearing cells. IL4-PE4E was
      extremely cytotoxic to highly purified anti-CD3-activated CD8+ T lymphocytes. The
      cytotoxic activity of this molecule was dependent on the activation state of CD8+
      T cells: 3- and 4-day activated T cells were very susceptible to the cytotoxic
      activity of IL4-PE4E compared with 0- to 2-day activated cells. PHA-activated
      lymphocytes and PBL activated in mixed lymphocyte reaction were also highly
      sensitive to IL4-PE4E. CD16+ and/or CD56+ highly purified NK cells or highly
      purified, IL-2-activated NK cells were also very sensitive to the cytotoxic
      effect of IL4-PE4E. IL-2-activated LAK cells had little susceptibility after 1
      day but were very sensitive to IL4-PE4E after 3 days. The cytotoxic effects of
      IL4-PE4E were mediated through a ligand receptor interaction because excess rIL-4
      abrogated these effects as did a neutralizing Ab to human IL-4. A chimeric mutant
      protein that can bind to IL-4 receptors but lacks the ability to inhibit protein
      synthesis was not cytotoxic to activated lymphocytes. The IL4-PE4E-mediated
      cytotoxicity of activated T cells correlated with the level of expression of IL-4
      receptors on these cells. CD8+ T cells activated for 3 days expressed the highest
      density of IL-4 receptors compared with 1- or 2-day activated cells. Among two
      chimeric toxins tested only IL4-PE4E was cytotoxic to 2-day anti-CD3-activated
      CD8+ T lymphocytes, whereas IL6-PE4E was not active at all. These studies suggest
      that human IL4 toxin could be a potent agent for the elimination of activated
      lymphocytes in allograft rejection, some autoimmune diseases, or treatment of
      lymphomas and leukemias.

PMID- 8144945
TI  - Enkephalin-containing peptides processed from proenkephalin significantly enhance
      the antibody-forming cell responses to antigens.
AB  - Highly conserved enkephalin containing peptides (ECPs) are selectively processed
      from proenkephalin, which is synthesized in both the neuroendocrine and immune
      systems. The reported regulatory effects within the central nervous system and
      the biologic release patterns from both activated lymphocytes and stimulated
      adrenal chromaffin cells suggest the ECPs may act as regulatory factors of the
      immune system. We tested the effects of three of the ECPs, Peptides F, E, and B,
      on the in vitro Ab-forming cell (AFC) response murine splenocytes to antigenic
      challenge. In contrast to the immunosuppressive effects of the pentapeptide
      enkephalins, physiologic concentrations of the ECPs significantly enhanced the
      AFC response to both T cell-dependent and T cell-independent Ags. The effects are
      not sensitive to competition by the opiate receptor antagonist, naloxone,
      suggesting cell surface interactions that do not involve classical opiate
      receptors. These studies provide evidence that the effects are mediated through T
      cells rather than B cells. Peptide F-treated splenocytes also showed a
      significant enhancement of the AFC response to suboptimal Ag concentrations,
      suggesting a mechanism of action in which the ECPs may act to lower the threshold
      of activation of the effector cell. These results suggest that the ECPs are
      physiologically important modifiers of the humoral immune response. Given their
      release patterns and demonstrated action on the in vitro immune response, the
      proenkephalin-derived ECPs have the potential to be involved in both paracrine
      and autocrine regulatory networks within the immune system and as a positive
      immunoregulatory effect from the neuroendocrine system.

PMID- 8144946
TI  - Induction of B cell and T cell tolerance in vivo by anti-CD23 mAb.
AB  - T cell tolerance can be induced by B cell presentation of Ags to naive T cells.
      To further characterize this mechanism of T cell tolerance induction, we have
      investigated the effects of injecting mice with an intact rat IgG2a Ab, which
      binds to the B cell low-affinity Fc epsilon receptor (CD23), on the
      responsiveness of B cells and T cells to rat IgG2a. Our observations indicate
      that 1) intravenous, subcutaneous, or intraperitoneal injection of this Ab
      induces antigen-specific B cell and T cell tolerance; 2) both forms of tolerance
      are induced more completely by injection of rat IgG2a anti-CD23 mAb than by
      injection of an equal dose of a control rat IgG2a Ig; and 3) reduced
      responsiveness to Ag is seen as early as 1 to 3 days after anti-CD23 mAb
      injection and reaches maximum levels by 7 days after injection. Although
      tolerance induced by the injection of soluble proteins has been reported to be
      characterized by reduced production of IL-2 and IFN-gamma, but normal production
      of IL-4, injection of mice with rat IgG2a anti-mouse CD23 mAb greatly decreases
      the IL-4 response to a rat IgG2a immunogen that normally induces a large IL-4
      response.

PMID- 8144947
TI  - In vivo activation of naive T cells by antigen-presenting B cells.
AB  - In vivo experiments were performed to determine if the cross-linking of mlg on
      antigen-presenting B cells could induce them to present Ag to naive T cells in a
      stimulatory rather than a tolerogenic fashion. Mice were injected with a foreign
      mAb to a B cell Ag (Fc epsilon RII or CR1), and/or a self-anti-IgD mAb. Injection
      of either mAb alone failed to induce an Ab response; however, simultaneous
      injection of the foreign anti-B cell mAb plus the self-anti-IgD mAb stimulated a
      large response. Inasmuch as injection of the anti-IgD mAb should not have
      facilitated transfer of the foreign mAb to dendritic cells, this observation
      suggests that cross-linking of B cell mlg can induce B cells to acquire the
      ability to present Ag to naive T cells in an activating manner. Furthermore, when
      injected with anti-IgD mAb, both foreign anti-B cell mAbs were more potent in
      inducing Ab responses in this system than were isotype-matched control mAbs,
      consistent with the hypothesis that T cells were activated by Ag-presenting B
      cells. Results of dose-response and cell transfer studies, however, suggested
      that stringent cross-linking of B cell mlg on large numbers of B cells is
      required for B cell Ag presentation to induce T cell activation rather than
      tolerance. Therefore, these observations suggest that professional APCs usually
      are required to activate naive T cells, and that B cell Ag presentation can only
      activate naive T cells under unusual circumstances.

PMID- 8144948
TI  - Induction of allograft tolerance in rats by an HLA class-I-derived peptide and
      cyclosporine A.
AB  - T cell recognition of MHC molecules initiates a cascade of events resulting in
      allograft rejection. CTLs damage the graft by targeting nonself-MHC class I
      molecules. We and others have previously shown that small synthetic peptides
      corresponding to regions of certain MHC class I molecules can inhibit the CTL
      response against MHC class I alloantigens in vitro. Here we report that rat heart
      allografts survived survived indefinitely when transplanted into recipients
      treated with a synthetic peptide corresponding to residues 75-84 of (B7.75-84) in
      combination with a subtherapeutic dose of cyclosporine A. Furthermore, this
      treatment induced long-term donor-specific tolerance that was mediated by anergic
      cells, indicating that such peptides may have potential as therapeutics for human
      organ transplantation.

PMID- 8144949
TI  - Thymic CD45 tyrosine phosphatase regulates apoptosis and MHC-restricted negative
      selection.
AB  - The acquisition of immunologic self-tolerance is governed, in part, by selection
      mechanisms that occur during intrathymic T cell ontogeny. Although considerable
      data exist for the molecular basis of mature T cell signal transduction, the
      enzymes that participate in thymic TCR selection processes have remained
      unidentified. We report that augmented thymic expression of the CD45R0 protein
      tyrosine phosphatase increased the efficacy of TCR-mediated apoptosis and MHC
      restricted negative selection of HY TCRs in vivo. Additionally, augmented CD45R0
      expression resulted in the activation of endogenous p56lck tyrosine kinase in
      CD4+CD8+ thymocytes. These results identify a cellular enzyme, the CD45R0 protein
      tyrosine phosphatase, involved in the regulation of apoptosis and TCR selection
      mechanisms during CD4+CD8+ thymocyte differentiation.

PMID- 8144950
TI  - Human primary immune response in SCID mice engrafted with human peripheral blood
      lymphocytes.
AB  - Severe combined immune deficient (SCID) mice were engrafted with human peripheral
      blood lymphocytes (Hu-PBLs) after treatment with anti-asialo GM-1 antiserum and
      radiation. This pretreatment facilitates high level of Hu-PBL engraftment in the
      SCID mice spleen. The next day, the Hu-PBL-SCID mice were immunized with either
      keyhole limpet hemocyanin (KLH), or carbohydrate Ag STn (AcNeu-alpha 2-alpha 6
      Gal NAc-0) conjugated to KLH or protein of circumsporozoite malaria parasite
      (CSP), in a mixture of complete and incomplete Freund's adjuvant (1:10 v/v). The
      mice were bled 14 to 16 days after immunization, and the sera analyzed for STn-,
      KLH-, and CSP-specific human IgG and IgM Abs. The results showed that the
      immunized animals had a significantly higher titer of Ag-specific human IgG and
      IgM Abs compared to the control Hu-PBL-SCID mice. No significant Ab cross
      reactions were detected between sera from KLH-, STn-, and CSP-vaccinated Hu-PBL
      SCID mice. Depletion of either human CD4+ or CD8+ cells, in Hu-PBL-SCID mice,
      showed that CD4+ cells were essential for the primary immune response, but
      depletion of CD8+ cells had no influence on the titer of Ag-specific human IgG
      and IgM Abs.

PMID- 8144951
TI  - TCR cross-linking induces CTL death via internal action of TNF.
AB  - TCR-mediated stimulation can result in either activation or apoptosis, raising
      the question of what the mechanisms of these opposing effects might be. Here we
      demonstrate that microinjection of Ab specific for TNF inhibits activation
      induced cell death, implicating TNF in anti-CD3-induced apoptosis. Induction of
      CTL in the presence of antisense TNF oligodeoxynucleotides inhibits TNF secretion
      and cell death after stimulation with anti-CD3. Incubation of cells with IL-2 for
      48 h before stimulation protects from anti-CD3-induced death, whereas the
      presence of IL-2 during anti-CD3 treatment is without effect.

PMID- 8144952
TI  - Superantigen-like properties of an antibody bispecific for MHC class II molecules
      and the V beta domain of the T cell antigen receptor.
AB  - A working model for the action of superantigens (SAg) is that they are simple
      proteins having binding sites for both MHC class II molecules and the V beta
      domain of the TCR. Binding of a SAg to both molecules cross-links the TCR,
      inducing a biologic response. In this study, we have tested this working model
      using a SAg mimic consisting of a hybrid Ab bispecific for the murine MHC class
      II molecule I-E and the V beta 8 domain of the murine TCR. The bispecific Ab
      activates V beta 8-bearing T cells only in the presence of I-E molecules on APC
      when tested in vitro. The effect of the bispecific Ab in vivo revealed both
      clonal deletion and a reduction in the responsiveness of V beta 8-bearing T
      cells. Thus, the results suggest that molecules distinct from SAg that can bind
      to both MHC class II molecules and the V beta domain of the TCR can mimic the
      biologic actions of a SAg.

PMID- 8144953
TI  - TGF-beta mediates natural suppressor activity of IL-2-activated lymphocytes.
AB  - In addition to generating cells with non-MHC-restricted cytotoxic activity that
      is characteristic of lymphokine-activated killer (LAK) cells, in vitro cultures
      of lymphocytes with relatively high concentrations of IL-2 generate cells that
      simultaneously exhibit two distinct types of suppressor activities: veto, the
      ability of cells to specifically suppress generation of allo-CTL against their
      own histocompatibility Ags; and natural suppression, the ability of these same
      cells to nonspecifically suppress the generation of allo-CTL against both their
      own and unrelated cell surface Ags. In contrast to veto, which is known to
      require cell-cell contact between veto-active cells and precursors of CTL,
      natural suppression is known to be mediated by soluble factors. To identify and
      characterize suppressor factors that might mediate the natural suppressor
      activity of IL-2-activated lymphocytes, murine spleen cells were cultured with
      1000 U/ml IL-2, and, after varying periods of incubation, their LAK cytolytic
      activity and natural suppressor activity was determined and cell supernatants
      were collected and tested for their effects on mixed lymphocyte culture-induced
      generation of allo-CTL. Like the IL-2-activated lymphocytes themselves,
      supernatants of these cells nonspecifically inhibited mixed lymphocyte culture
      induced generation of allo-CTL. Rabbit anti-TGF-beta specifically neutralized the
      suppressive effects of both LAK cell supernatants and the IL-2-activated
      lymphocytes themselves. These findings indicate that TGF-beta is the primary
      mediator of the natural suppressor activity of IL-2-activated lymphocytes.

PMID- 8144954
TI  - Monomeric homologue of mammalian CD28 is expressed on chicken T cells.
AB  - A mAb recognizing a 40- to 44-kDa monomeric molecule on the surface of chicken T
      cells was used to screen a cDNA expression library made from Con A-stimulated
      chicken spleen cells. The sequence of the cDNA obtained encoded a molecule having
      50% amino acid sequence identity with mammalian CD28, but the cysteine residue
      involved in the inter-chain bridge of the mammalian CD28 homodimer was not
      conserved in the chicken sequence. The molecule produced in transfected COS-7
      cells was also recognized by another mAb that had previously been thought to
      recognize an avian homologue of CD2. The sequence data establish that this
      molecule is a homologue of mammalian CD28 in the strict evolutionary sense.

PMID- 8144955
TI  - Human CD45RC specificity. A novel marker for T cells at different maturation and
      activation stages.
AB  - The different isoforms of CD45 seem to play an important role in thymocyte
      maturation and T cell activation and function. To investigate the particular
      contribution of CD45-exon C (exon 6) to human T cell development, we first
      investigated the expression of the CD45-exon C isoforms on different human
      lymphoid cell populations. A wide panel of mAbs against the different isoforms of
      CD45 was generated by immunizing mice with purified human CD45. Two of these mAbs
      (RP1/12 and RP2/19) selectively recognized mouse 300-19 pre-B cells that had been
      transfected with CD45 cDNA that contained exon C, suggesting that epitopes
      recognized by these mAbs are dependent on the expression of exon C.
      Immunofluorescence analysis of PBLs showed that CD45RC is expressed at high
      levels on B, NK, and CD8+ T cells, although a subset of CD4+ T cells was found to
      be negative. Activation of PBMCs and purified NK cells resulted in down
      regulation of CD45RC, which took place in a coordinate manner involving both down
      regulation of the expression of CD45RA and CD45RB and up-regulation of CD45R0.
      Two-color immunofluorescence analyses showed that thymocytes expressing CD45RC
      were CD1-to lo, CD3hi and HLA class Ihi, typical markers of mature thymocytes.
      Accordingly, immunohistochemical analysis of a normal thymus showed that whereas
      the anti-CD45RA mAb stained only a subset of medullary thymocytes, the anti
      CD45RC mAb stained the majority of medullary thymocytes. Thymocytes that bear
      CD45RA also express CD45RC, but do not express CD45RO; a subset of CD45 RA- RO+
      thymocytes was also detected. Immunoprecipitation of CD45 molecules from both
      PBMC and thymocyte cell lysates with mAbs against the different specificities of
      this molecule revealed that the RC determinants are found on CD45 polypeptides of
      220 and 205 kDa that also bear RB or both RB and RA determinants, respectively.
      Together these results support both the existence of a tight regulation of the
      expression of CD45 specificities during lymphocyte activation and thymocyte
      maturation and also that CD45RC is selectively expressed by mature medullary
      thymocytes during T cell ontogeny.

PMID- 8144956
TI  - Association of human class I MHC alleles with the adenovirus E3/19K protein.
AB  - A panel of HLA-A and -B locus products was analyzed for their ability to
      associate with the adenovirus E3/19K (E19) protein in a co-immunoprecipitation
      assay. Three general categories of binding were identified. HLA-A2.1 and -B7 bind
      very well to E19. Compared with A2.1, 6- to 30-fold less E19 was associated with
      HLA-A3, -A1, and -Aw69; 50- to 150-fold less E19 was associated with HLA-Aw68, 
      B27, and -Bw58. Digestion with endoglycosidase H indicated that all levels of
      association resulted in inhibition of intracellular transport and processing,
      however, a fraction of Aw68, B27, and Bw58 escaped from intracellular retention.
      In contrast to the human class I molecules analyzed, transport of the murine H
      2Dd molecule was not inhibited in the presence of E19. Hybrid class I molecules,
      in which exons encoding domains of A2.1 and H-2Dd had been exchanged, were used
      to define the regions of A2.1 required for E19 association. The alpha 1 and alpha
      2 domains of A2.1 contain the minimum residues necessary for both stable
      association with E19 and subsequent inhibition of transport. A hybrid construct
      containing only the alpha 2 domain of A2.1 associated weakly with E19, but its
      post-translational processing was completely inhibited. In contrast, although a
      construct containing only the alpha 1 domain of A2.1 also associated weakly with
      E19, its intracellular transport was slowed rather than completely inhibited.
      Taken together, these results indicate that residues in both the alpha 1 and
      alpha 2 domains of A2.1 and Dd can influence stable binding of E19, with the
      phenotypic changes dominated by the origin of the alpha 2 domain.

PMID- 8144957
TI  - The regulatory complex of HLA class I promoters exhibits locus-specific
      conservation with limited allelic variation.
AB  - The extensive genetic polymorphism of the classical MHC class I molecules
      provides an important distinguishing feature of the host's immune system. They
      influence the selection and function of effector cells against tumor and virally
      infected cells. In these cells, class I molecules are often selectively
      suppressed. This suppression is locus specific and, in certain cases, allele
      specific. We analyzed the HLA class I promoter sequences that include class I
      regulatory complex (CRC) in a total of 41 well-characterized HLA homozygous B
      lymphoblastoid cell lines, using locus-specific oligonucleotide probes
      complementary to the overlapping CRC elements. These include kappa B1, kappa B2,
      IFN response sequence, the putative negative regulatory element, and the HLA
      counterpart of the H-2RII region that contains the retinoid x receptor beta
      binding motif. The CRC of HLA promoters displayed locus-specific conservation;
      however, limited allelic variation was observed in each of the cis elements. In
      some, variations were apparently generated by gene conversion. The palindromic
      kappa B1 site, which has an active role in enhancing promoter activity, was found
      to be conserved in almost all HLA-A and -B alleles, but not in HLA-C. The core
      DNA binding motif for retinoid x receptor beta was absent within the HLA CRC
      region. Sequence analysis of promoters from HLA-A31, -B13, and -Cw1 genomic
      clones, as well as pairwise interallelic and intra-allelic comparison with those
      of published alleles, showed that locus-specific conservation extended throughout
      the promoter sequences. Locus specificity and the allelic variation seen in the
      CRC regions may provide a structural basis for the selective modulation of HLA
      class I genes.

PMID- 8144959
TI  - CD3 delta enhancer. CREB interferes with the function of a murine CD3-delta A
      binding factor (M delta AF).
AB  - Tissue-specific expression of the murine TCR/CD3-delta gene is regulated by
      multiple factors. Earlier, we reported that this gene has a tissue-specific
      enhancer at its 3' end that consists of two cis-acting elements, M delta A and M
      delta B. This study demonstrates that at least two independent factors bind to
      the 22 nucleotide long M delta A element. A T cell-specific factor termed M delta
      AF recognizes a 10-bp sequence TTCCATGACA, whereas the cAMP response element
      binding protein (CREB) recognizes an overlapping sequence TGACATCA. In vitro
      studies indicated that the 135-kDa M delta AF and the 43-kDa CREB competed for
      binding to the M delta A element. To test this competition in vivo, murine T
      cells (EL4) were cotransfected with a CREB expression plasmid and a reporter
      plasmid containing the M delta A element. The presence of an excess of CREB
      protein in the cell inhibited the CAT activity completely. This inhibitory effect
      of CREB could be overcome by cotransfection of an additional vector containing
      the somatostatin CRE site that prevented the overexpressed CREB protein from
      binding to the M delta A element. It is possible that the murine CD3-delta gene
      in T cells is regulated by the relative levels of the T cell-specific DNA binding
      protein M delta AF and the ubiquitous CREB in conjunction with other factors.

PMID- 8144958
TI  - Proteolytic processing of ovalbumin and beta-galactosidase by the proteasome to a
      yield antigenic peptides.
AB  - The identification of genes in the class II region of the MHC that are homologous
      to genes encoding subunits of the proteasome has led to intense interest in the
      possible role of this enzyme in the proteolytic processing of polypeptide Ags. We
      have tested the ability of the 20S proteasome to produce peptides that can be
      presented by class I molecules as targets for killing by OVA-specific and beta
      galactosidase-specific CTL clones. Samples of intact OVA and beta-galactosidase
      were subjected to digestion in vitro by 20S proteasome purified from bovine red
      cells and the resulting peptide mixtures were fractionated by reverse-phase HPLC.
      The fractions were tested for their ability to sensitize appropriate mouse target
      cells for lysis by specific CTL clones. In both cases, components that under all
      chromatographic conditions eluted with retention times indistinguishable from
      synthetic peptides representing known epitopes of the naturally processed
      proteins were found to be able to sensitize the target cells. Moreover, in the
      case of OVA, the presence of the expected target peptides was demonstrated
      directly by amino acid sequence and mass spectrometric analysis. The results
      demonstrate that the pure 20S proteasome is capable of generating antigenic
      peptides from two proteins for presentation by class I molecules without the
      participation of additional components of the protein degradation system. This
      finding is consistent with the hypothesis of proteasome involvement in Ag
      processing in vivo.

PMID- 8144960
TI  - Definition of specific peptide motifs for four major HLA-A alleles.
AB  - Allele-specific motifs for the human MHC class I molecules, HLA-A1, A3, A11, and
      A24 were characterized by three complementary approaches. First, amino acid
      sequence analysis of acid eluted peptide pools from affinity purified class I
      molecules defined putative motifs 9 or 10 amino acids in length and bearing
      critical anchor residues at position 2 and at the COOH-terminal. These motifs
      were distinct, with the exception of the HLA-A3 and A11 motifs that were very
      similar to each other. Second, the correctness of these putative motifs was
      verified by analyzing the binding capacity of polyalanine peptide analogues to
      purified HLA-A molecules. Several alternative anchor residues that were not
      obvious from the pooled peptide sequencing analysis were identified. Third,
      sequences of individual peptides eluted from HLA-A1, A11, and A24 were determined
      by tandem mass spectrometry. Nonamers were the predominant species, although
      peptides of 8, 10, 11, and 12 amino acids in length were also identified. These
      peptides displayed anchor residues predicted by the specific motifs at position 2
      and at the COOH-terminal, regardless of peptide length. Synthetic versions of the
      naturally processed peptides were shown to bind to the appropriate HLA-A alleles
      with IC50 values in the 0.3- to 200-nM range. A rational approach to search Ags
      with known amino acid sequences for epitopes restricted by some of the most
      common HLA-A types and of potential clinical importance is now feasible.

PMID- 8144961
TI  - Ig heavy chain extracellular spacer confers unique glycosylation of the Mb-1
      component of the B cell antigen receptor complex.
AB  - A unique functional role for the B cell Ag receptor, IgD, has not yet been
      identified. A number of properties of IgD, such as distinct intron-exon
      organization and a conserved pattern of developmental expression, suggest a
      selective evolutionary advantage for this receptor isotype. To explore structural
      features of IgD that may confer unique functions, chimeric Ag receptors were
      generated in which small segments of the IgD heavy chain membrane proximal
      regions were substituted for corresponding segments of the IgM heavy chain.
      Polypeptides that associate with the Ig receptors were analyzed. Mb-1/Ig-alpha, a
      signal transduction molecule, is known to be glycosylated in a distinct manner
      when associated with IgD compared to when associated with other isotypes. We
      report that this differential glycosylation results because one N-linked
      carbohydrate on Mb-1 fails to be processed into an Endo-H-resistant form when
      associated with IgM or IgG, whereas both N-linked carbohydrates are processed on
      Mb-1 associated with IgD. By preparing chimeric IgM-IgD heavy chains,
      substitution of the IgD extracellular spacer segment alone was found to be
      necessary and sufficient to confer an IgD-type glycosylation pattern on the Mb-1
      molecule. This altered glycosylation pattern, however, did not confer a
      detectable difference in calcium mobilization or in protein tyrosine
      phosphorylation upon receptor stimulation. Interestingly, a similar altered
      glycosylation pattern has been reported for the T cell Ag receptor complex in
      which carbohydrates on the CD3 delta-chain are fully processed in gamma delta-T
      cell receptors but only partially processed in alpha beta-T cell receptors.

PMID- 8144962
TI  - Preferential VH gene usage in rabbit Ig-secreting heterohybridomas.
AB  - B cells from leukemic rabbits preferentially use a single VH gene, VH1, in their
      VDJ gene rearrangements. To determine whether Ig-secreting B cells from normal
      rabbits also preferentially use VH1, we generated rabbit X mouse heterohybridomas
      that stably secreted rabbit Ig that expressed VHa allotypic specificities and
      analyzed the VH genes used in their VDJ gene rearrangements. We cloned the VDJ
      genes from nine heterohybridomas, and by comparing the restriction map of the DNA
      immediately 5' of the translational start site of these VDJ genes to that of the
      same region 5' of VH1, we showed that eight of the nine heterohybridoma clones
      use VH1. Comparison of the nucleotide sequences of the eight VH1-using VDJ genes
      with the nucleotide sequence of germ-line VH1 showed that each of them had
      somatically diversified. The diversified regions included clustered nucleotide
      changes and codon insertions and deletions, such as would be expected if the
      diversification process involved somatic gene conversion. We searched our
      database of germ-line VH genes for genes that could serve as donors for the gene
      conversion events, and we identified potential VH donor genes for five regions of
      diversification. One of these regions of diversification spanned at least 132 bp
      and included a codon insertion as well as 15 nucleotide changes. The data confirm
      that Ab diversity may be generated by a somatic gene conversion-like mechanism.
      The results directly demonstrate that Ig-secreting B cells from normal rabbits
      preferentially use VH1 in their VDJ gene rearrangements.

PMID- 8144963
TI  - Molecular characterization of human Ig heavy chain DIR genes.
AB  - Antibody VDJ recombination is ensured by evolutionarily conserved recombination
      signals (RS). The 12/23 rule postulates that only gene segments with
      asymmetrically spaced RS recombine with one another. Two unusually long D genes
      (170 bp) with irregular RS (DIR) have been reported in humans and have been
      postulated to participate actively in VDJ recombination, thus frequently
      contributing to the Ab heavy chain third hypervariable region (CDR3). However,
      the limited sequence information retained in the CDR3 along with significant
      sequence diversity has precluded an accurate assessment of the actual role and
      genomic diversity of DIR genes. Furthermore, DIR genes pose an interesting puzzle
      in terms of their precise mechanism of recombination because they possess
      multiple and imperfect RS, often located up to 30 bp away from the recombining
      fragment within the DIR coding region. Here we present conclusive evidence for
      the existence of additional human germ-line DIR genes and preliminary evidence
      that suggests the absence of DIR-like sequences in nonprimate animals. We also
      show that DIR genes are under the transcriptional control of VH-independent
      promoters and have the potential to encode a D mu protein of 105 amino acids.
      Finally, DIR genes seem at least in early fetal life to recombine preferentially
      through the conventional 3' RS.

PMID- 8144964
TI  - CD8 cells play a critical role in delayed type hypersensitivity to intact
      Cryptococcus neoformans.
AB  - Although cell-mediated immunity is critical for optimal host defense to C.
      neoformans, the role of T lymphocyte subsets is complex and poorly understood.
      CD8 cells are important both for optimal host defense against C. neoformans, and
      for expression of delayed type hypersensitivity (DTH). Because host defense
      correlates with the ability to mount a DTH response to C. neoformans, the current
      studies were performed to determine the mechanism by which CD8 cells participate
      in DTH. Mice were immunized by the intratracheal route with live C. neoformans,
      or by the subcutaneous route with heat-killed C. neoformans. Mice were depleted
      of CD8 cells in vivo by administration of mAb. After challenge with soluble
      cryptococcal Ag, the DTH response was quantified as footpad swelling. We found
      that mice depleted of CD8 cells before immunization were unable to express DTH.
      Mice depleted of CD8 cells after immunization but before challenge also were
      unable to express DTH. Splenocytes of mice depleted of CD8 cells in vivo, before
      immunization, failed to transfer DTH to naive, undepleted mice. Immune
      splenocytes depleted of CD8 cells in vitro also failed to transfer DTH to naive,
      undepleted mice. These data indicate that CD8 cells were necessary during the
      challenge and immunizing phases of DTH, and were necessary for expression of DTH.
      However, CD8 cell depletion did not abrogate DTH in mice immunized with either
      soluble cryptococcal Ag in complete Freund's adjuvant, or sheep red blood cells,
      which are mediated by CD4 cells. These data suggest that CD8 cells play a
      critical role in the cell-mediated immune response to C. neoformans. Based on
      this information, it may be possible to protect hosts with deficiencies of CD4
      cells, such as in AIDS, by designing immunizing strategies for stimulating CD8
      cells.

PMID- 8144965
TI  - Contribution of antibody-secreting cells induced in mucosal lymphoid tissues of
      pigs inoculated with respiratory or enteric strains of coronavirus to immunity
      against enteric coronavirus challenge.
AB  - Two antigenically related porcine coronaviruses, transmissible gastroenteritis
      virus (TGEV) which infects primarily the intestinal tract and causes severe
      diarrhea, and porcine respiratory coronavirus (PRCV) which infects the
      respiratory tract and causes subclinical or mild respiratory infections,
      presented a unique opportunity to study the interrelationship of gut-(GALT) and
      bronchus-associated lymphoid tissues (BALT) and their contribution to protective
      immunity against TGEV infection. Pigs were inoculated oral-nasally with TGEV or
      with PRCV at eleven days of age and challenged 24 days later with TGEV. All pigs
      initially given TGEV developed diarrhea and were completely protected against
      disease upon challenge. In contrast, pigs given PRCV had no clinical disease and
      shed virus in nasal secretions only; after challenge, 5 of 12 pigs developed
      diarrhea. Virus-specific IgG and IgA Ab-secreting cells (ASC) were enumerated by
      ELISPOT in the mesenteric and bronchial lymph nodes, spleens, and gut lamina
      propria at challenge and various post challenge days. Before challenge, in pigs
      exposed to TGEV, IgA-ASC in the duodenum and jejunum constituted the major ASC
      response. Conversely, PRCV-exposed pigs had mainly IgG-ASC in bronchial lymph
      nodes, with low ASC responses in the gut. After challenge, numbers of IgG-ASC
      increased rapidly in the gut lamina propria and mesenteric lymph nodes of only
      PRCV-primed pigs. Our results suggest that virus-specific IgG-ASC precursors
      derived in BALT of PRCV-primed pigs may migrate to the gut in response to TGEV
      challenge and contribute to the partial protection observed. The presence of IgA
      ASC in the gut lamina propria of TGEV-primed pigs at the time of challenge
      correlated with complete protection against TGEV challenge. Thus a dichotomy
      exists in the BALT and GALT ASC responses; immunization via BALT induced a
      systemic type of response (IgG-ASC) and provided imperfect protection against an
      enteric pathogen, whereas immunization via GALT induced IgA-ASC and provided
      complete protection.

PMID- 8144966
TI  - Co-ligation of CD31 and Fc gamma RII induces cytokine production in human
      monocytes.
AB  - The CD31 (PECAM-1) cell surface glycoprotein is considered to be involved in
      intercellular recognition and adhesion. Cytokines play a major role in cellular
      interactions, and therefore it was of interest to study whether engagement of
      CD31 affects synthesis and release of proadhesive cytokines. Here we demonstrate
      that immobilized CD31 mAb 1B5 induces the release of TNF-alpha, IL-1 beta, and IL
      8 from human PBMCs. CD11b mAb VIM12 and HLA-D mAb VID1, both of which are of the
      same Ig subclass as mAb 1B5 (IgG1), as well as nonbinding isotype control mAb
      VIAP, were ineffective. That the effect was caused by the mAb, but not endotoxin
      contamination, was shown by negative Limulus amebocyte lysate tests and coculture
      with polymyxin B, which did not abolish TNF-alpha release. Cytokine production
      through intact mAb 1B5 was completely blocked by soluble F(ab) fragments of anti
      IgG Fc gamma RII mAb IV.3, suggesting a significant contribution of that FcR.
      Cross-linking of neither CD31 nor Fc gamma RII molecules with the respective
      F(ab) fragments induced TNF-alpha release, but nonbinding control IgG1 Ab was
      able to restore the response of PBMC to 1B5 F(ab) fragments, when both Ab
      preparations were coated concomitantly. Therefore, only coligation of CD31 and Fc
      gamma RII appears to transduce activation signals leading to cytokine production.
      Our findings thus indicate a novel functional aspect of CD31 molecules that might
      play an important role in the propagation of an ongoing immune response as well
      as in the regulation of cell-cell interactions during inflammatory reactions.

PMID- 8144967
TI  - Interaction of Staphylococcus aureus with human neutrophils and the down
      regulation of TNF receptors.
AB  - We have shown previously that pre-exposure of neutrophils to TNF significantly
      enhanced their killing of opsonized Staphylococcus aureus. We now demonstrate
      that the ability of TNF to enhance the bactericidal activity is dependent on
      preincubation time; enhancement was still evident when TNF and bacteria were
      added simultaneously to neutrophils but if TNF addition was delayed by 5 min, no
      enhancement was seen. Evidence is presented that suggests that this could be
      related to a down-regulation of TNF receptors by the bacteria, but in addition,
      the release of TNF receptor fragments may contribute to the inhibition observed.
      Scatchard analyses demonstrated a decrease from approximately 3000 TNF receptor
      (receptor binding) sites per cell to 450 following treatment with S. aureus, but
      essentially no change in receptor affinity. Using mAb directed against the type A
      (75 kDa) receptor (utr-1) and the type B (55 kDa) receptor (htr-9), it was found
      that the expression of both receptors was decreased following treatment with the
      bacteria. The time course of loss of these receptors showed that the surface
      expression of both molecules was markedly decreased by 5 min which correlated
      with the loss in ability of TNF to enhance the bactericidal activity. In contrast
      to changes seen in the binding of TNF, similarly treated neutrophils showed
      essentially no change in the binding of radiolabeled tripeptide FMLP and, if
      anything, an increase in the expression of the CD11b Ag (CR3 receptor). When
      another phagocytic stimulus was used, opsonized fungi (Torulopsis glabrata), a
      similar depression of TNF binding was also found, but opsonized sheep
      erythrocytes had no effect on the TNF binding, suggesting that the effects on the
      TNF receptor cannot be explained simply on the basis of particle phagocytosis.

PMID- 8144968
TI  - Cell-surface protein identified on phagocytic cells modulates the C1q-mediated
      enhancement of phagocytosis.
AB  - C1q, a subunit of the first component of the classical C pathway, binds to
      specific cells of the immune system, triggering a variety of cellular responses.
      To identify the functional C1qR on phagocytic cells, mAbs were generated by
      immunization with either C1q-binding proteins isolated from U937 cells or intact
      U937 cells. Immunoprecipitation followed by Western blot analysis demonstrated
      that three mAbs, designated R139 (IgG2b), R3 (IgM), and U40.3 (IgG1), recognize
      the same 100,000 M(r) protein (126,000 M(r) under reducing conditions). These
      mAbs also co-immunoprecipitate CD43 from detergent extracts of U937, consistent
      with the possibility that this C1qR is a multi-subunit structure. Two Abs, R3 and
      R139, but not U40.3, consistently inhibited the enhancement of phagocytosis by
      monocytes adhered to either C1q or the collagen-like fragment of C1q (C1q-CLF).
      Interestingly, binding inhibition studies demonstrated that neither R139 nor
      U40.3 blocked the binding of [125I]C1q-CLF to U937 cells, whereas R3 did inhibit
      35 to 45% of the binding of [125I]C1q-CLF to these cells. Thus, the three mAbs
      recognize distinct epitopes of a 100,000 M(r) polypeptide that is a component of
      the monocyte C1qR that modulates phagocytosis. All three mAbs recognize the
      extracellular domain of the molecule on neutrophils, monocytes, and U937 cells,
      but were not reactive with CEM or RAJI cells, T and B lymphoblastoid cell lines,
      respectively. Furthermore, none of these three mAbs inhibited or mimicked the C1q
      mediated stimulation of superoxide production by neutrophils, suggesting that the
      C1qR that mediates the enhancement of phagocytosis differs in at least some
      critical parameter from the C1qR that mediates superoxide generation by the
      neutrophil.

PMID- 8144969
TI  - Differential roles of two types of the TNF receptor in TNF-induced cytotoxicity,
      DNA fragmentation, and differentiation.
AB  - Two different types of TNF receptors, the p60 receptor with a molecular mass of
      60 kDa and the p80 receptor with a mass of 80 kDa, have been identified. TNF
      exhibits a wide variety of biologic actions, but which receptor is responsible
      for these biologic actions is not well characterized. In the present study, we
      examined the roles of the p60 and p80 receptors in three different TNF-induced
      biologic actions: 1) cytotoxicity; 2) DNA fragmentation; and 3) differentiation
      to macrophages. Analysis of TNF actions on various tumor cell lines revealed that
      TNF-induced cytotoxicity occurred in cells that expressed the p60 receptor,
      irrespective of expression of the p80 receptor. In contrast, DNA fragmentation
      and differentiation were observed only in cells that expressed both receptor
      types. Additionally, the specific Ab to each receptor were used to examine the
      roles of both receptors in the myelogenous leukemia cell line, ML-1a. Anti-p60 Ab
      alone showed cytotoxicity but little DNA fragmentation and differentiation, and
      anti-p80 Ab alone showed no effects. When these Abs were added in the presence of
      TNF, each independently, and almost completely, inhibited TNF-induced DNA
      fragmentation and differentiation. We also found that both Abs together
      synergistically induce differentiation and DNA fragmentation. These results
      indicate that signals through the p60 receptor are essential to induce
      cytotoxicity, but signals through both the p60 and p80 receptors are necessary,
      and act synergistically, for DNA fragmentation and differentiation.

PMID- 8144970
TI  - Slow release of soluble TNF receptors by monocytes in vitro.
AB  - In this study, we investigated the release of soluble(s) TNF-R by PBMC in vitro.
      T cell activation by mAb anti-CD3, as well as activation with phorbol esters
      (PMA), enhanced the release of both sTNF-R55 and sTNF-R75 by PBMC. In contrast to
      shedding of TNF-R by neutrophils upon activation, release of sTNF-R by PBMC
      proved to be a relatively slow process, reaching a plateau after 2 days of
      culture. Monocytes appeared to be the main source of the released sTNF-R, whereas
      activation of purified T cells induced only a minor release of sTNF-R as compared
      with the whole cell population. To unravel the mechanism, a number of cytokines
      were added during a 2-day culture of cells. IL-10 enhanced sTNF-R levels with
      similar kinetics as mAb anti-CD3 and PMA, whereas the other cytokines tested did
      not affect the release of sTNF-R by PBMC, pure T lymphocytes, or purified
      monocytes, either activated or not. Conversely, inhibitors of cytokines were
      added during the activation period to study the effect of endogenously produced
      cytokines on sTNF-R release. mAb anti-IL-10 and IL-1ra partly sTNF-R release,
      whereas other inhibitors did not affect the release. The results obtained in
      vitro may extend our insight in the mechanism via which sTNF-R are enhanced in
      vivo during inflammatory reactions.

PMID- 8144971
TI  - Determination of the primary structures of human skin chymase and cathepsin G
      from cutaneous mast cells of urticaria pigmentosa lesions.
AB  - This study establishes the primary structure of human skin chymase and provides
      further evidence for the presence of a cathepsin G-like proteinase within human
      mast cells. The amino acid sequence of human skin chymase was established by
      protein methods and by analysis of PCR amplification products obtained with cDNA
      derived from urticaria pigmentosa (UP) lesions. UP is a disease characterized by
      skin lesions containing high numbers of mast cells. Proteolytic digests of human
      chymase purified from normal skin yielded 10 resolvable peptides that were
      sequenced by automated Edman degradation. The amino acid sequences for these
      peptides combined with the sequence obtained for the protein's NH2-terminal
      region (35 residues) accounted for 137 residues of the human skin chymase
      sequence. This partial amino acid sequence corresponded to the sequence of human
      heart chymase, a proteinase isolated from heart tissue with immunologic and
      hydrolytic properties similar to skin chymase. PCR amplification of UP-derived
      cDNA with primers based on the cDNA structure of heart chymase demonstrated a
      single amplification product of expected size which was subcloned and sequenced.
      The amino acid sequence (135 residues) deduced from this product was identical to
      that of heart chymase in the region between the primers. This sequence, along
      with that established for the purified protein, constituted 99% of the heart
      chymase primary structure, strongly indicating that human skin and heart chymases
      have identical primary structures. Amplification of the same UP-cDNA with primers
      coding for the NH2- and COOH-terminal sequences of human neutrophil cathepsin G
      also produced a specific amplification product which was sequenced. The deduced
      amino acid sequence between the primers was identical to that reported for
      neutrophil cathepsin G, indicating that the protein of cutaneous mast cells
      previously shown to be immunologically cross-reactive with neutrophil cathepsin G
      has a comparable amino acid sequence. UP-cDNA demonstrating amplification
      products for cathepsin G did not demonstrate amplification products for human
      neutrophil elastase, suggesting that the cathepsin G PCR amplification product
      was not derived from neutrophils or monocytes possibly contaminating the lesion.
      These studies provide further evidence that human skin mast cells contain two
      different chymotrypsin-like proteinases.

PMID- 8144972
TI  - Binding of the terminal mannosyl units of lipoarabinomannan from a virulent
      strain of Mycobacterium tuberculosis to human macrophages.
AB  - Recent studies from this laboratory have demonstrated that macrophage
      phagocytosis of virulent strains (Erdman and H37Rv), but not the attenuated H37Ra
      strain of Mycobacterium tuberculosis, is mediated by phagocyte mannose receptors
      (MR) in addition to complement receptors (CR1 and the leukocyte integrins CR3 and
      CR4). Lipoarabinomannan (LAM) is a major surface lipoglycan of M. tuberculosis.
      LAM from the Erdman strain (Man-LAM) contains mannose oligosaccharides at the
      terminal portions of the molecule. This study investigated the ability of ManLAM
      to serve as a microbial ligand in adherence to human monocyte-derived macrophages
      (MDM). Polystyrene microspheres were coated with known amounts of purified
      ManLAM, LAM without the terminal mannosyl units from an avirulent mycobacterium
      (AraLAM), lipomannan (LM), or buffer and incubated with MDM monolayers in the
      absence of serum. The presence of LAM on microspheres was confirmed by indirect
      immunofluorescence studies. Microspheres coated with ManLAM demonstrated a more
      than threefold increase in adherence to MDM when compared with microspheres
      coated with AraLAM, LM, or buffer and the low levels of adherence of microspheres
      in the latter three groups were comparable. Compared with control monolayers,
      selective down-modulation of MDM MR on a mannan substrate abrogated the enhanced
      adherence of microspheres mediated by ManLAM. Adherence of microspheres coated
      with AraLAM, LM, or buffer was not influenced by MR modulation. To confirm the
      importance of the terminal mannosyl units of ManLAM in the enhanced adherence of
      ManLAM microspheres to MDM, these units were selectively removed by
      exomannosidase treatment. The structure of LAM products before and after enzyme
      treatment was confirmed by high performance anion exchange chromatography with
      pulsed amperometric detection. Removal of the terminal mannosyl units abolished
      the capacity of ManLAM to mediate enhanced adherence of microspheres to MDM.
      Finally, preincubation of Erdman M. tuberculosis with CS-40, a mAb directed
      against LAM, resulted in a consistent inhibition of adherence of the bacteria to
      MDM (up to 49% inhibition), confirming a role for ManLAM on intact bacteria in
      adherence to MDM. Thus, we provide evidence for a novel receptor-ligand pathway
      in phagocytosis of M. tuberculosis that consists of MR on macrophages and
      mannosyl units at the terminal end of ManLAM, a major microbial surface
      lipoglycan.

PMID- 8144973
TI  - Lipopolysaccharide and cytokine augmentation of human monocyte IgA receptor
      expression and function.
AB  - Receptors for IgA (Fc alpha R) are found on phagocytic cells in the peripheral
      blood and tissues associated with mucosal areas where IgA Abs constitute a major
      line of defense. Because Fc alpha R are capable of triggering protective
      functions of monocytes and neutrophils, such as phagocytosis and the oxidative
      burst, they may be important in amplifying the antimicrobial effects of IgA.
      Various cytokines play a role in regulating function and FcR expression of
      monocytes, macrophages, and neutrophils. The present studies examine the
      modulation of monocyte Fc alpha R by LPS and cytokines. LPS strongly up-regulated
      monocyte Fc alpha R expression. TNF and IL-1, produced in response to LPS,
      promoted Fc alpha R increase, as did GM-CSF; whereas IFN-gamma down-regulated Fc
      alpha R. Increased receptor expression was accompanied by augmented IgA-mediated
      phagocytosis. An increase in Fc alpha R-specific mRNA was detected in monocytes
      treated with TNF, IL-1, GM-CSF, and LPS; whereas message was reduced in cells
      treated with IFN-gamma. Monocyte-derived macrophages and cells of the Monomac 6
      monocyte-like line expressed greater numbers of Fc alpha R than monocytes but
      were less responsive to LPS and TNF. Cell lines THP-1 and U937, which expressed
      similar or lower levels of Fc alpha R than monocytes, displayed an increase in Fc
      alpha R in response to LPS and, to various degrees, to TNF, IL-1, and GM-CSF.
      These results indicate that Fc alpha R on monocytes are modulated by endotoxin
      and an array of cytokines distinct from those that regulate expression of FcR for
      IgG.

PMID- 8144974
TI  - Pulmonary epithelial cells facilitate TNF-alpha-induced neutrophil chemotaxis. A
      role for cytokine networking.
AB  - TNF-alpha and neutrophils are postulated to play important roles in several
      inflammatory lung diseases. Thus, we examined TNF-alpha-induced neutrophil
      migration through polycarbonate filters and human pulmonary type II-like
      epithelial (A549) cells cultured as monolayers on these filters. TNF-alpha
      induced both dose- and time-dependent migration of neutrophils across both
      barriers, but migration across A549 cells was much greater than that across naked
      filters. Migration of neutrophils across both barriers was completely inhibited
      by anti-TNF-alpha. Furthermore, supernatants of TNF-alpha (10(-9) M)-stimulated
      A549 monolayers induced threefold greater migration of neutrophils across naked
      filters than 10(-9) M TNF-alpha itself, suggesting release of soluble chemotactic
      factor(s). Pretreatment of A549 monolayers with actinomycin D inhibited both the
      production of soluble chemotactic factors and TNF-alpha-induced transcellular
      migration. Supernatants from TNF-alpha-stimulated A549 cells contained
      significant concentrations of IL-8, and coincubation of these supernatants with
      anti-IL-8 decreased supernatant-induced chemotaxis. Finally, coincubation of TNF
      alpha with anti-IL-8 during transmigration experiments partially inhibited
      neutrophil migration through A549 monolayers. Therefore, pulmonary type II
      epithelial cells facilitate TNF-alpha-induced transcellular migration of
      neutrophils through the production of soluble protein synthesis-dependent
      chemotactic factors, including IL-8. These data support the concepts of cytokine
      networking in inflammatory cell recruitment and an active role for pulmonary
      epithelium in lung inflammation.

PMID- 8144975
TI  - Nitric oxide regulates endotoxin-induced TNF-alpha production by human
      neutrophils.
AB  - We studied the effect of nitric oxide on LPS-induced TNF-alpha production by
      human neutrophils. Human neutrophils exposed to LPS and IFN-gamma did not show
      measurable increases in intracellular cyclic GMP (cGMP). However, cGMP increased
      upto 30-fold (p < 0.01) in neutrophils incubated with both sodium nitroprusside
      (SNP), an exogenous source of nitric oxide, and N-acetylcysteine (NAC), which
      increases the bioavailability of nitric oxide; this increase indicates that
      neutrophils contain a nitric oxide-sensitive guanylate cyclase. SNP, with or
      without NAC, did not increase TNF-alpha production in human neutrophils cultured
      in medium alone. However, LPS-dependent TNF-alpha production was increased by
      exposure to SNP (p < 0.05); this effect was further increased by the addition of
      NAC (p < 0.02). IFN-gamma greatly increased LPS-mediated TNF-alpha production by
      human neutrophils (p < 0.01), and SNP plus NAC was found to further augment this
      production (p < 0.01). The up-regulation of TNF-alpha production by nitric oxide
      was not associated with increased amounts of LPS-induced TNF-alpha mRNA, and was
      not reproduced by exposing neutrophils to cGMP analogues. These data suggest that
      nitric oxide released by endothelial and vascular smooth muscle cells may exert a
      paracrine effect on human neutrophils and augment the inflammatory response in
      sepsis by increasing the production of cytokines. Although the mechanism of this
      effect remains unknown, it does not seem to be dependent on cGMP or increased
      levels of TNF-alpha mRNA.

PMID- 8144976
TI  - Immunogenic and antigenic properties of an HIV-1 gp120-derived multiple chain
      peptide.
AB  - An HIV-1 envelope protein gp120-derived monomeric peptide (amino acid residues
      419-439) and its homologous multiple chain peptide (MCP) construct were compared
      for immunogenicity in mice. The Abs stimulated by the MCP recognized epitopes on
      the MCP that were not present on the homologous monomer. The anti-419-439 MCP
      sera recognized a conformational determinant on the native envelope glycoprotein,
      as indicated by: 1) detection of native but not denatured recombinant envelope
      glycoprotein by ELISA and dot blot and 2) reaction with infected cell lines
      expressing gp120 on their surface as detected by flow cytometry. In contrast, the
      anti-monomer sera were highly specific for the monomer and recognized the
      envelope glycoprotein at lower titers. The low reactivity of the anti-monomer
      sera with the envelope glycoprotein was not decreased by denaturation.
      Reciprocally, murine antiserum to HIV-1 envelope glycoprotein gp160 recognized
      the MCP construct but not the homologous monomeric peptide. The data indicate
      that the MCP construct forms additional antigenic determinants not present on the
      homologous monomer, and that the anti-419-439 MCP Abs recognize a conformational
      determinant on the envelope glycoprotein not recognized by Abs against the
      homologous monomer. Furthermore, antisera against another envelope-derived MCP
      (amino acid residues 105-117) also recognize conformational determinants on the
      envelope glycoprotein, whereas antisera against the homologous monomeric peptide
      do not.

PMID- 8144977
TI  - Influence of H-2 class II antigens on the development of murine AIDS.
AB  - Inbred strains of mice differ markedly in their relative susceptibility to the
      development of lymphoproliferation and immunodeficiency, a syndrome termed mouse
      AIDS (MAIDS), after infection with the LP-BM5 mixture of murine leukemia viruses
      (MuLV). The etiologic virus in this mixture is replication defective (BM5def) and
      encodes only a variant gag protein. Genetic determinants of resistance and
      susceptibility to induction of MAIDS reside both within and outside the MHC. In
      strains with C57BL background genes, the MHC haplotypes associated with
      resistance to disease include d and a, whereas haplotypes b, s, and q are
      associated with sensitivity. Previous studies showed that MHC class I genes (H
      2Dd, H-2Ld) mapping in the D end of H-2 and other genes mapping proximal to the D
      end determine resistance to MAIDS. This paper examines the nature of these non-D
      end MHC genes using assays of MHC recombinant and transgenic mice. We demonstrate
      that expression of E alpha d confers significant resistance to MAIDS, even in
      mice that do not express H-2Dd/H-2Ld. Unexpectedly, we found that E alpha
      polymorphisms can significantly influence resistance, with H-2b mice bearing E
      alpha d as a transgene having greater resistance to MAIDS than mice bearing an E
      alpha k transgene. E alpha d-mediated resistance to MAIDS was associated with
      decreased levels of the BM5def genome in splenic DNA, suggesting that E alpha
      genes exert their effect by enhancing antiviral activity.

PMID- 8144978
TI  - BUB/BnJ (H-2q) is a TCR deletion mutant mouse strain (TCR V beta a, KJ16-) that
      is susceptible to type II collagen-induced arthritis.
AB  - Type II collagen-induced arthritis (CIA) in mice is an animal model of autoimmune
      inflammatory arthritis. Arthritis is induced in susceptible strains of mice (H-2q
      and H-2r) after immunization with heterologous or autologous type II collagen in
      CFA. Induction of CIA is T cell dependent and a restricted usage of TCR V beta
      genes has been found in the arthritic joints and lymph nodes of mice with CIA.
      However, genes within the MHC are not the only determinants of susceptibility to
      CIA as SWR/j, AU/ssJ (both H-2q) and RIIIS/J(H-2r) mice are resistant to the
      induction of CIA. These strains of mice are TCR V beta chain genes deletion
      mutants (TCR V beta a and TCR V beta c haplotypes) and it was hypothesized that
      these mice are resistant to CIA because of the absence of a particular set of V
      beta TCR genes that are genomically deleted in these strains of mice. We now show
      that BUB/BnJ mice (H-2q) are T cell subsets deficient because of the genomic
      deletion of TCR V beta 5, 8, 9, 11, 12, and 13 sub-families. Our data demonstrate
      that despite the deficiency in T cell subsets from genomic deletion of TCR V beta
      genes, BUB mice are highly susceptible to the development of CIA. These results
      indicate that genomic deletion of certain TCR V beta genes alone is not in itself
      sufficient to confer resistance to CIA. These results further suggest that other
      unknown gene(s) must also contribute to the induction of CIA.

PMID- 8144979
TI  - Chemically selected subclones of the CEM cell line demonstrate resistance to HIV
      1 infection resulting from a selective loss of NF-kappa B DNA binding proteins.
AB  - To delineate cellular genes that are required for optimal HIV-1 infection, CEM
      cells were subjected to treatment with the chemical mutagen ethylmethanesulfonate
      (EMS) and subclones were selected based on their increased resistance to HIV-1
      infection and reduced syncytium formation, despite relatively normal CD4
      expression (20,000 to 25,000 receptors/cell). Two subclones with this phenotype
      demonstrated a diminished capacity of HIV-1 long terminal repeat-chloramphenicol
      acetyl transferase expression either after treatment with the protein kinase C
      activator PMA, or through Tat-mediated transactivation. In this study, we show
      that the cellular levels of the NF-kappa B DNA binding proteins (but not AP1 or
      SP1) are markedly reduced in these cell mutants both at the mRNA and protein
      levels, resulting in reduced nuclear localization of p50/p65 after PMA induction
      or treatment with the lymphokine TNF-alpha. Transient reconstitution with a
      plasmid expressing p50 resulted in partial recovery of PMA-inducible LTR
      chloramphenicol acetyl transferase expression. These data suggest that, at least
      in the CEM T cell line, a selective reduction in the NF-kappa B DNA binding
      proteins is sufficient to curtail HIV-1 infection.

PMID- 8144980
TI  - Characterization of cat dander-specific T lymphocytes from atopic patients.
AB  - Fel d I, the major cat dander allergen, is recognized by serum IgE of more than
      80% of all cat-allergic patients. Because IgE synthesis by B lymphocytes is under
      the control of T lymphocytes, we studied the specificity and lymphokine
      production profiles of cat dander-specific T lymphocytes. Polyclonal cat dander
      specific T cell lines were found to react with purified Fel d I, but not with cat
      albumin, the only other characterized cat allergen. Similarly, within a panel of
      CD4+ T lymphocyte clones (TLC) that was generated from these cat dander-specific
      T cell lines, 5 of 16 TLC were found to react with Fel d I, and 0 of 16 with cat
      albumin. The remaining 11 TLC were shown to recognize at least two different
      proteins. In general, the TLC had a high IL-4/IFN-gamma production ratio, and
      could recognize the cat dander extract in an HLA-DR, HLA-DQ, or HLA-DP restricted
      manner. In addition, five distinct T cell epitopes of Fel d I were identified by
      using a panel of overlapping synthetic peptides of both chains of Fel d I. The
      data presented here indicate that, even though multiple proteins in cat dander
      extract are recognized by T lymphocytes of allergic patients, Fel d I, the major
      IgE binding allergen, is also important in T cell activation. The fact that the
      cat-specific TLC are Th2-like indicates that these cells may play an important
      role in the pathophysiology of allergic responses to cat allergens. However, the
      diversity of HLA-class II restriction of cat dander- and Fel d I-specific TLC and
      the presence of multiple T cell epitopes in the allergen may complicate future
      immunotherapies.

PMID- 8144982
TI  - Effects of incubation with liposomes at different temperatures on cultured
      melanoma cells (M14).
AB  - A melanoma cell line (M14) was used in order to investigate the effect of
      hyperthermia on the mechanisms of interaction between liposomes and cultured
      cells. The treatment was performed by adding different concentrations of
      multilamellar liposomes (L-alpha-dipalmitoylphosphatidylcholine, stearylamine and
      cholesterol in the ratio 7:2:1) to cell cultures which were then incubated at
      37.0 or 41.5 degrees C for 2 h. The damage induced by liposome treatment in
      normothermia or hyperthermia was evaluated by determining cell survival and by
      electron microscopy. When different concentrations of liposomes were used, a dose
      dependent impairment of cell survival was observed. An enhancement of the
      cytotoxic effect was observed when the treatment was performed at 41.5 degrees C.
      This effect went on even after 24 h from the end of the treatment, but the
      difference between cells treated in normothermia and hyperthermia was remarkably
      reduced. The mechanism of the liposome-plasma membrane interaction has been
      investigated by electron microscopy. Our observations demonstrated that the outer
      bilayer of the multilamellar liposomes was capable of fusing with the plasma
      membrane, inducing changes in its fluidity and molecular organization. Following
      this process the inner liposomal bilayers entered the cell. These effects seemed
      to be favoured when the treatment was performed under mild hyperthermic
      conditions, accounting for the synergic cytotoxic action displayed by the
      liposome-hyperthermia association.

PMID- 8144981
TI  - Effect of hyperthermia on the central nervous system: a review.
AB  - Experimental data show that nervous tissue is sensitive to heat. Animal data
      indicate that the maximum tolerated heat dose after local hyperthermia of the
      central nervous system (CNS) lies in the range of 40-60 min at 42-42 x 5 degrees
      C or 10-30 min at 43 degrees C. No conclusions concerning the heat sensitivity of
      nervous tissue can be derived from clinical studies using localized hyperthermia.
      The choice whether or not to exceed the critical heat dose, as derived from
      laboratory studies, in clinical practice is very much dependent on the clinical
      situation such as the anatomical site and volume of the tissue involved, and
      prior therapy. Data on clinical application of whole body hyperthermia (WBH) show
      that nervous tissue can withstand a slightly higher heat dose than after
      localized heating, which might be the result of developing thermal resistance
      during treatment. Expression of thermotolerance was observed in the spinal cord
      of laboratory animals. After WBH in man at a maximum between 40 and 43 degrees C
      for 6 h-30 min CNS complications were reported, but other complications seemed to
      be more life-threatening. Most studies indicate that impairment of the CNS after
      WBH was not due to direct heat injury to the brain or spinal cord, but was
      secondary as a result of physiological changes. Heat, at least if applied shortly
      after X-rays, enhances the response of nervous tissue to radiation. Neurotoxicity
      of chemotherapeutic drugs does not seem to be a limiting complication in
      hyperthermia if combined with chemotherapy, but only few data are available. The
      limited clinical experience shows that safe hyperthermic treatment of CNS
      malignancies or tumours located close to the CNS seems feasible under appropriate
      technical conditions with adequate thermometry and taking the sensitivity of the
      surrounding normal nervous tissue into account.

PMID- 8144983
TI  - Mild step-down heating causes increased levels of HSP68 and of HSP84 mRNA and
      enhances thermotolerance.
AB  - Mammalian cells exhibit increased sensitivity to hyperthermic temperatures of 38
      42 degrees C after an acute high-temperature heat shock; this phenomenon is known
      as thermo-sensitization or the step-down heating effect. In order to determine
      whether the increase of heat shock mRNA after heat stress can be
      thermosensitized, we studied the induction of the mRNA of HSP68 and of HSP84
      after application of step-down heating (SDH) in Reuber H35 rat hepatoma cells.
      SDH consisted of a pretreatment of 30 min at 41.5, 42.5 or 43.5 degrees C,
      followed by a continuous incubation at a lower hyperthermic temperature (40 or 41
      degrees C). After mild pretreatment (30 min at 41.5 degrees C) the mRNA level of
      HSP68 was increased by subsequent incubation at 40 degrees C, although incubation
      at 40 degrees C alone had no effect. This increase was even more pronounced at 41
      degrees C. An increase in the level of HSP84 mRNA was also observed after mild
      pretreatment (41.5 degrees C/30 min) followed by 41 degrees C post-incubation.
      Interestingly, an enhanced occurrence of thermotolerance was also observed upon
      application of mild step-down heating (42 degrees C/30 min-40 degrees C-43.5
      degrees C/60 min). In contrast, cell cultures treated for 30 min at 43.5 degrees
      C (a temperature which induces an increase in HSP mRNA levels) showed an
      inhibited or delayed synthesis of HSP mRNA when post-treated at 40 or 41 degrees
      C. Under these conditions the development of thermotolerance did not take place
      either. With respect to the effect of step-down heating on HSP mRNA levels as
      well as on thermotolerance development, our data imply that a distinction should
      be made between 'mild' and 'severe' pretreatment temperature of the step-down
      heating protocol.

PMID- 8144984
TI  - Development and testing of SAR-visualizing phantoms for quality control in RF
      hyperthermia.
AB  - A new prototype of an elliptical standard phantom with fat-equivalent walls and a
      lamp matrix for SAR (specific absorption rate) visualization has been developed.
      This paper outlines the manufacture of solid components based upon either
      polyester resin or epoxy resin, as well as the adjustment of their electrical
      conditions (epsilon r, sigma) by admixtures of carbon and/or aluminium powder.
      Visualizing sensors (LED = light-emitting diodes, miniature lamps) are evaluated
      with respect to their transformation of electric field strength into light.
      Standard SAR patterns of the hyperthermia system BSD-2000 have been
      semiquantitatively assessed by the visualizing technique (power stepping method)
      and quantitatively by E field sensor scans. Extracted iso-SAR distributions are
      in good agreement with E field sensor scans performed with a lamp sensor coupled
      to a fibre or using a dipole probe with high resistive leads. The requirement for
      periodic quality control of SAR patterns of RF (radio frequency) hyperthermia
      systems is demonstrated. Comparisons between techniques are given, specifically
      with respect to the LED phantom of Schneider and van Dijk.

PMID- 8144985
TI  - Multi-applicator hyperthermia system description using scattering parameters.
AB  - Hyperthermia systems using electromagnetic phased arrays have often been
      investigated from a SAR distribution point of view. One of the problems in these
      systems is that the achieved SAR distribution is different from the intended one
      because of changes in the generator signals due to mutual coupling between
      applications. The use of circuit theory and S-parameters in the description of an
      N-applicator phased array system is introduced in this paper, and a compact
      matrix equation giving excitation as a function of generator signals is derived.
      Measurement of the S-parameters is discussed using a phased array deep heating
      system (Danish Hyperthermia Foundation (DHF)) as an example. In a phantom
      experiment a significant improvement in the SAR distribution is demonstrated when
      the developed method is applied.

PMID- 8144986
TI  - Phase I/II trial of preoperative thermoradiotherapy in the treatment of urinary
      bladder cancer.
AB  - Between April 1984 and September 1988, preoperative radiotherapy or
      thermoradiotherapy was administered to 49 patients with bladder cancer (T1-4N0M0;
      UICC classification, 1987). Twenty-one patients were preoperatively treated by
      radiotherapy alone, with 4 Gy per fraction and three fractions per week to a
      total dose of 24 Gy (TDF = 53, group 1). The other 28 patients were treated by
      the same radiotherapy regimen in combination with hyperthermia (group 2).
      Regional hyperthermia was administered for 35-60 min immediately after
      irradiation (two sessions per week to a total of four sessions) using an 8 MHz RF
      capacitive heating device. Group 2 was divided into group 2 (high), in which the
      average intravesical temperature (T(av)) was > 41.5 degrees C, which was the mean
      value, and group 2 (low) with a T(av) < 41 x 5 degrees C. Group 2 (high) showed a
      significantly higher incidence of down-staging and tumour degeneration than both
      group 1 and group 2 (low). In addition, the local recurrence rate was lower and
      survival time was longer in group 2 than in group 1, although not significantly
      so. In particular, the patients with T3-4 or grade 3 bladder cancer in group 2
      had a longer average survival than those in group 1, although the difference was
      not significant. The toxicity associated with hyperthermia was pain during
      treatment, and complications were not serious.

PMID- 8144987
TI  - Effects of intraoperative hyperthermia on peripheral nerves: neurological and
      electrophysiological studies.
AB  - The tolerance of peripheral nerves to heat may limit the heat dose which can be
      applied to tumours. This may be particularly important in intraoperative
      hyperthermia (IOHT) for pelvic and retroperitoneal tumours. Furthermore the
      effects of hyperthermia alone must be known before its effects can be assessed in
      combination with irradiation. In this study injury to sciatic nerves was
      evaluated in 30 beagle dogs for 1 year following IOHT. IOHT was performed using a
      water circulating hyperthermia device with multichannel thermometry system.
      Neurological and electrophysiological examinations were done before, during and
      after IOHT treatment. Electrophysiological examinations showed a significant
      decrease in sciatic nerve conduction velocity and potential amplitude immediately
      after 60 min of heating for all temperatures. The greatest decrease in conduction
      velocity was observed for a temperature of 45 degrees C. Full recovery of nerve
      conduction velocity was observed 3 weeks following hyperthermia for all dogs
      except for those exposed to 45 degrees C. Neurological findings correlated with
      electrophysiological results. All five dogs which had nerve exposed to 45 degrees
      C for 60 min had severe neurological changes, with recovery taking place between
      3 and 11 months after treatment. Based on these results it appears that
      temperatures to the peripheral nerve exceeding 44 degrees C for 1 h are likely to
      cause significant, but not necessarily permanent, nerve injury.

PMID- 8144988
TI  - A case-matched control study of intrahepatoarterial chemotherapy in combination
      with or without regional hyperthermia for treatment of primary and metastatic
      hepatic tumours.
AB  - The efficacy of the combined application of intrahepatoarterial (IHA)
      chemotherapy and regional hyperthermia for the treatment of unresectable hepatic
      tumours was studied in a case-matched, retrospective control study. Well-matched
      pairs of patients with the same or similar background factors, who had been
      treated with IHA chemotherapy plus hyperthermia (group A; n = 32) and with IHA
      chemotherapy alone (group B; n = 32) were included in this study. In group A,
      partial responses (PRs) were found in 2 of 8, 4 of 8, and 5 of 16 patients with
      hepatocellular carcinoma, metastatic gastric cancer, and metastatic colorectal
      cancer, respectively. In group B, PRs were found in 1 of 8, 3 of 8, and 5 of 16
      patients with those diseases, respectively. Overall, PRs were found in 12 (37%)
      and 9 (28%) of 32 patients in groups A and B, respectively; progressive disease
      was found in 6 (19%) in group A and in 12 (38%) in group B. These results
      indicate that this combination therapy is of therapeutic benefit in the treatment
      of unresectable hepatic tumours.

PMID- 8144989
TI  - Influence of water bolus temperature on measured skin surface and intradermal
      temperatures.
AB  - Temperature measurements utilizing thermometry probes placed on the skin surface
      are often used clinically to assess temperatures for the purposes of power
      control and evaluating treatment efficacy. There is a question, however, as to
      what extent applicator temperature-controlled liquid coupling boluses can create
      temperature gradients which can cause significant differences between
      measurements taken by sensors placed on the skin surface and the actual
      temperature of the tissue beneath. To address this question, experiments were
      conducted with human subjects instrumented with surface and shallowly implanted
      temperature sensors. Microwave applicators with circulating bolus water set at 21
      and 41 degrees C were used to induce a temperature gradient in depth in the
      superficial tissue by thermal conduction. No microwave energy was applied. The
      average measurement offset at 41 degrees C was 15% of the difference in
      temperature between the interstitially measured skin temperature and the coupling
      bolus temperature, towards the temperature of the coupling bolus. The
      corresponding offset with coupling boluses set near 21 degrees C was 32%.
      Different water bolus types and volumes were observed to induce different
      percentage offset errors.

PMID- 8144990
TI  - Heat protection by deuterium oxide of heat sensitive and wild-type Chinese
      hamster ovary cells.
AB  - The ability of deuterium oxide (D2O) to protect a heat-sensitive and
      thermotolerance-impaired Chinese hamster ovary (CHO) mutant cell line, HS-36
      (Harvey and Bedford 1988), from heat killing was examined and compared to the
      parent CHO 10B cell line (WT). Both non-thermotolerant (NT) and thermotolerant
      (TT) G1 populations were examined. D2O differentially protected the NT cell lines
      from heat killing, with thermal protection ratios (D0) of 2 x 5 and 4 x 3 for HS
      36 and WT cells, respectively. D2O provided additional protection to TT cells,
      but now protected the TT HS-36 cells more than the TT WT cells when the thermal
      protection ratios of TT cells are compared with those of NT cells (1.15 versus
      0.82). The differential protection from heat of the mutant and wild-type lines by
      D2O may be useful in studies of induced lesions in proteinaceous cellular systems
      (e.g. the nuclear matrix, cytoskeleton and plasma membrane) using these two
      paired cell lines.

PMID- 8144991
TI  - Effects of heat and amino acid supplementation on the uptake of arginine and its
      incorporation into proteins in Escherichia coli.
AB  - Hyperthermic treatment reduces protein synthesis and modifies amino acid
      transport in Escherichia coli. The present study examined the role of nutrient
      availability on these processes. Cultures of E. coli in log phase were aliquoted
      into growth medium with or without complete amino acid supplementation and
      exposed to 37, 44, or 48 degrees C for 10 min. Amino acid supplementation
      increased radiolabelled arginine uptake at 48 degrees C when compared with
      unsupplemented cells. Exposure to 48 degrees C also reduced protein synthesis in
      both groups by at least 50% as reflected by labelled arginine incorporation. Two
      dimensional gel electrophoresis indicated that this heat-related decrement in
      synthesis was most apparent in basic proteins. Total density analysis of the
      fluorographs demonstrated reductions in basic proteins of 15% at 44 degrees C and
      89% at 48 degrees C, while acidic proteins only showed an 80% reduction at 48
      degrees C. Amino acid supplementation appears to raise the baseline, but not to
      modify the final results of hyperthermia-induced inhibition of protein synthesis.
      The sensitivity of basic protein synthesis seems to be a key event in this
      process.

PMID- 8144992
TI  - Dialysis-related amyloidosis.

PMID- 8144993
TI  - The functional significance of induction of heme oxygenase by oxidant stress.

PMID- 8144994
TI  - Sex hormones, complement-mediated platelet damage, and hemostasis.

PMID- 8144995
TI  - Differentiation of intestinal epithelial cells: lessons from the study of
      intestine-specific gene expression.

PMID- 8144996
TI  - Current issues in tuberculosis.

PMID- 8144997
TI  - Prospects for oral iron chelation therapy.

PMID- 8144998
TI  - Serum beta 2-microglobulin concentration in dialysis patients: importance of
      intrinsic renal function.
AB  - We retrospectively analyzed serum beta 2-microglobulin (beta 2M) levels in
      dialysis patients at our institution from 1986 through 1991 to determine the
      clinical significance of serum beta 2M levels in dialysis patients and to provide
      further insight into the pathogenesis of beta 2M-associated dialysis arthropathy.
      We analyzed the relationship between serum beta 2M values can the dialysis
      modality (hemodialysis and continuous ambulatory peritoneal dialysis [CAPD]), the
      duration of dialysis therapy, the type of hemodialyzer used, and the level of
      intrinsic glomerular filtration rate (GFR). The most important relationship
      observed in all dialysis patients was a significant inverse relationship between
      intrinsic GFR and serum beta 2M values. For all dialysis patients (hemodialysis
      and CAPD), serum beta 2M values were highest when the intrinsic GFR was less than
      2.1 ml/min. There were no differences in serum beta 2M values between
      hemodialysis patients and CAPD patients or among patients using different types
      of cellulose-based hemodialyzers. As patients changed use from cellulose-based
      dialyzers to polysulfone dialyzers, there was no decline in serum beta 2M values.
      Exclusive treatment with polysulfone dialyzers for 9 to 12 months after
      initiation of long-term dialysis also led to no differences in serum beta 2M
      values compared with those in patients using cellulose-based dialyzers. At very
      low levels of intrinsic GFR (< 2.1 ml/min), hemodialysis patients using
      polysulfone dialyzers had lower levels of serum beta 2M than hemodialysis
      patients using cellulose-based dialyzers; CAPD patients also had lower levels of
      serum beta 2M than cellulose dialyzer-treated hemodialysis patients when the
      intrinsic GFR was less than 2.1 ml/min. All hemodialysis patients using cellulose
      dialyzers and CAPD patients were categorized at last follow-up as having
      definite, probable, or no evidence of beta 2M-associated dialysis arthropathy on
      the basis of clinical and radiographic criteria. We noted no significant
      differences in serum beta 2M values, regardless of the clinical diagnosis with
      regard to beta 2M-related amyloidosis. Patients with beta 2M amyloidosis had
      undergone dialysis therapy for a longer duration and had a larger cumulative
      exposure to beta 2M (the product of average serum beta 2M values and months of
      dialysis, or "beta 2M-months"). We conclude that the most important determinant
      of serum beta 2M values in dialysis patients is the remaining level of intrinsic
      GFR. At extremely low levels of GFR, use of polysulfone dialyzers or CAPD may
      lead to lower levels of serum beta 2M. Our analysis indicates that the duration
      of dialysis and cumulative exposure to beta 2M (beta 2M-months) are important
      factors in the development of clinically evident beta 2M amyloidosis.

PMID- 8144999
TI  - Heme oxygenase does not protect human cells against oxidant stress.
AB  - The induction of heme oxygenase in cells under conditions of oxidative stress has
      been hypothesized to represent a cellular antioxidant defense mechanism. The
      objectives of this study were to characterize the induction of heme oxygenase by
      the oxidant stress-inducing quinone agent menadione (2-methyl-1,4-naphthoquinone)
      and to elucidate the roles of basal and induced heme oxygenase enzyme activities
      in menadione-induced DNA damage and growth inhibition in human MCF-7 cells. Time-
      and dose-dependent inductions of heme oxygenase messenger RNA and enzyme activity
      in menadione-treated MCF-7 cells were demonstrated. Intracellular and
      extracellular bilirubin concentrations were less than 100 nmol/L and were not
      altered when heme oxygenase was induced. The roles of the basal and induced heme
      oxygenase enzyme activities in menadione-mediated DNA damage were evaluated by
      means of the heme oxygenase competitive inhibitor tin protoporphyrin. Inhibition
      of the basal heme oxygenase enzyme activity by tin protoporphyrin resulted in a
      decrease in the number of menadione-induced DNA breaks and an attenuation of the
      cellular growth inhibition caused by menadione. Induced heme oxygenase did not
      protect MCF-7 cells from menadione-induced DNA breaks. Basal heme oxygenase
      enzyme activities in two cloned menadione-resistant cell lines were significantly
      less than that measured in a menadione-sensitive parental MCF-7 cell line.
      Collectively, these data do not support a protective role for basal or induced
      heme oxygenase enzyme activities against oxidant stress-related DNA strand
      breakage or cytotoxic effects engendered by menadione in human cells.

PMID- 8145000
TI  - Complement-mediated fragmentation and lysis of opsonized platelets: ender
      differences in sensitivity.
AB  - It was reported that elevated levels of platelet microparticles (PMPs) in
      patients with immune thrombocytopenic purpura (ITP) were associated with
      decreased bleeding, and in some cases with small vessel thromboses (J Lab Clin
      Med 1992; 119:334). To investigate the possible role of complement in PMP
      production in ITP, an in vitro assay was developed to simulate ITP: platelets
      were opsonized with well-defined monoclonal antibodies against glycoprotein
      IIb/IIIa, of immunoglobulin G (alpha-CD41), and of immunoglobulin M (alpha-Plt-1)
      class, then exposed to serum as a source of complement. PMP generation and lysis
      were monitored by flow cytometer, by release of lactic dehydrogenase, and by
      generation of procoagulant activity. These effects were largely abolished by
      heating the serum (30 minutes, 65 degrees) or by incubation with alpha-C1q,
      confirming the role of complement. At low concentrations of serum, both
      monoclonal antibodies promoted PMP shedding in a concentration-dependent manner
      without loss of platelet population; at higher concentrations, extensive lysis
      occurred, but marked variations in resistance to lysis were observed in platelets
      from different individuals. The PMPs produced were associated with increased
      procoagulant activity, as measured by the Russell's viper venom test. The
      immunoglobulin M antibody was more potent than the immunoglobulin G antibody in
      promoting lysis, and the resulting PMPs had greater procoagulant activity. To
      clarify the variation seen in platelets from different donors, data was sorted on
      the basis of gender, with the finding that women's platelets are significantly
      more sensitive to complement-mediated damage than men's. This may explain in part
      why ITP is three to four times more prevalent in women than in men. We conclude
      that complement activation is the most likely explanation for the elevated level
      of PMPs often seen in patients with ITP and sometimes associated with thrombosis
      and that the determining factors are the concentration and nature of antibody as
      well as individual differences in sensitivity to complement-mediated damage.
      Because complement activation can occur without participation of antibody,
      complement activation may also be the cause of elevated PMP levels seen in other
      thrombotic disorders not involving platelet-specific antibodies.

PMID- 8145001
TI  - Identification of a 68 kd surface antigen of Mycobacterium avium that binds to
      human macrophages.
AB  - Infection caused by Mycobacterium avium is the major cause of bacteremia in
      patients with AIDS. A critical event in the initiation of a variety of bacterial
      infections is the adherence of bacteria to host cell surfaces, which is often
      brought about by the interaction of specific molecules on the bacterial surface
      with host cell surface receptors. In the present study, a sonicate of M. avium
      was used to isolate monocyte-binding proteins by affinity chromatography with
      CNBr-Sepharose-4B coupled to extracts of monocytes. A 68 kd protein present on
      the surface of M. avium was identified as one of nine monocyte-binding proteins.
      This protein was isolated and further characterized. The N-terminal amino acid
      sequence (22 residues) of the protein was determined and was found to exhibit
      strong homology with the 65 kd heat shock proteins of M. tuberculosis, M. leprae,
      and M. bovis. However, a previously characterized monoclonal antibody directed
      against a 66 kd antigen of M. avium was found to cross-react with the 68 kd
      protein from M. avium but not with the 65 kd proteins from M. leprae and M.
      bovis, suggesting that the 68 kd antigen may differ from the 65 kd proteins of M.
      leprae and M. bovis with respect to certain epitopes. In an in vitro inhibition
      assay, the 68 kd protein was found to compete with the attachment of intact
      fluorescein isothiocyanate-labeled M. avium to monocyte-derived macrophages,
      inhibiting this attachment in a dose-dependent manner up to 42%. The 65 kd
      proteins of M. leprae and M. bovis, on the other hand, did not appear to inhibit
      this attachment substantially (13.9% and 14.6%, respectively). These results
      suggest that the 68 kd protein of M. avium may be involved in binding to
      receptors on macrophages and help in the attachment of the organism to its host
      cell.

PMID- 8145002
TI  - Persistence of mobile receptors on surface- and suspension-activated platelets.
AB  - We examined the distribution of glycoprotein Ib (GPIb) and glycoprotein IIb-IIIa
      (GPIIb-IIIa) receptors on suspension- and surface-activated platelets before and
      after exposure to thrombin (1 U/ml, 10 minutes). Frozen thin sections prepared
      from fixed suspension-activated platelets or grids containing fixed surface
      activated platelets were stained with specific antibodies to GPIb
      (antiglycocalicin) and GPIIb-IIIa (AP2 or 7E3), incubated with the corresponding
      gold-labeled secondary antibody, and examined in the electron microscope. GPIb
      and GPIIb-IIIa were evenly distributed on membranes of resting and suspension
      activated platelets. GPIb and GPIIb-IIIa were present in the open canalicular
      system (OCS) of resting and, more prominently, in dilated OCS channels of
      thrombin suspension-activated platelets. On surface-activated platelets more
      intense labeling for GPIb was observed along pseudopods of dendritic cells
      whereas GPIIb-IIIa receptors were slightly increased over the peripheral zone.
      Morphometric study of labeling on fully spread, surface-activated platelets
      revealed that the density of GPIb increased significantly after thrombin
      treatment (60.7 +/- 13.1 vs 40.9 +/- 8.3 gold particles/microns 2, p < 0.05). A
      flow cytometry assay employing the same antiglycocalicin antibody revealed no
      down-regulation or clearance of GPIb after exposure of platelets to thrombin.
      GPIIb-IIIa distribution on spread platelets after exposure to thrombin remained
      basically unchanged (28.4 +/- 10.5 vs 32.6 +/- 10.9 particles/microns2 in
      nonactivated platelets). These findings indicate that clearance of GPIIb-IIIa and
      GPIb on suspension-activated platelets does not take place to the extent
      suggested in previous studies and does not occur spontaneously or after thrombin
      activation on surface-activated platelets. Although the presence of mobile
      receptors on platelets is essential for spreading on immobile surfaces and each
      other, their clearance to the OCS is not a fundamental mechanism regulating
      adhesion.

PMID- 8145003
TI  - Differential effects of ferritin, calcium, zinc, and gallic acid on in vitro
      proliferation of human glioblastoma cells and normal astrocytes.
AB  - In vitro, when using low concentrations of ferritin (ng/ml) or CaCl2
      (micrograms/ml), multiplication of a human, 1,3-bis-(2-chloroethyl)-1-nitrosourea
      (BCNU)-resistant glioblastoma cell line (U251) is enhanced 1.5 to 2 times more
      actively than multiplication of a normal astrocyte line (CRL 1656). Ferritin and
      Ca2+ ions exhibit a marked effect on DNA isolated from these cells: glioblastoma
      DNA relaxation is strongly increased (as evidenced by increased 260 nm
      ultraviolet absorbance), being from 5 to 6 times that of astrocyte DNA, which
      remains only slightly affected. Under identical experimental conditions, Zn2+ and
      gallium ions selectively inhibit glioblastoma cell multiplication but at the same
      concentrations do not inhibit astrocyte multiplication. Ultraviolet absorbance
      measurements demonstrate that both of these agents condense relaxed glioblastoma
      DNA in vitro. Zn2+ or gallium ions added to culture medium containing stimulatory
      concentrations of ferritin or Ca2+ ions selectively and strongly inhibit
      enhancement of glioblastoma cell multiplication by these mitogens while not
      affecting normal multiplication of astrocytes.

PMID- 8145004
TI  - Side effects of iron supplements in blood donors: superior tolerance of heme
      iron.
AB  - Regular blood donors were enrolled in a double-blind, parallel group study to
      evaluate the side effects of two iron supplements, one containing both heme iron
      and non-heme iron (Hemofer, 2 tablets = 18 mg iron/day), the other non-heme iron
      only (Erco-Fer; 1 tablet = 60 mg iron/day). No differences were found between the
      two alternatives in regaining predonation iron status as measured by serum
      ferritin and hemoglobin levels. Despite this therapeutic equivalence,
      participants' symptom diaries showed substantial differences in the side effects
      for the two treatments. The frequency of constipation (p < 0.05) and the total
      incidence of all side effects (p < 0.01) were significantly higher for non-heme
      iron when compared with the heme iron-non-heme iron combination and a placebo.
      The study demonstrates that a low-dose iron supplement containing both heme iron
      and non-heme iron (Hemofer) has fewer side effects when compared with an
      equipotent, traditional non-heme iron supplement.

PMID- 8145005
TI  - Influence of hypercalcemia on ionized calcium concentration in pancreatic juice
      of the dog.
AB  - Calcium concentration of pancreatic juice depends on secretion of calcium bound
      to enzymatic proteins or calcium diffusion from interstitial fluids. To evaluate
      the relative magnitude of these pathways, we studied the influence of
      hypercalcemia on ionized calcium (Ca++) in dog pancreatic juice. Pancreatic juice
      was collected during basal secretion and during stimulation by secretin or
      secretin plus caerulein in control conditions and under CaCl2 infusion. [Ca++]
      was measured by selective electrodes. Saturation of juice in CaCO3 was
      calculated. In stimulated juice, total calcium concentration ([CaT]) and [Ca++]
      were unchanged by hypercalcemia. In basal juice, composition was profoundly
      modified by hypercalcemia because [CaT] (3.31 +/- 0.89 mmol/L vs 1.80 +/- 0.44
      for controls), [Ca++] (1.44 +/- 0.37 mmol/L vs 0.84 +/- 0.24 mmol/L for
      controls), and the index of saturation in CaCO3 (5.2 +/- 2.4 vs 2.9 +/- 1.8 for
      controls) increased significantly. Protein concentration was unchanged. This
      suggests that in basal conditions, the relationship between plasma and juice
      calcium levels is due to passive interstitial Ca++ diffusion through the
      pancreatic ducts. In accordance with the hypothesis of a restricted calcium
      diffusion, the effects of hypercalcemia were flow rate dependent, being less
      pronounced when basal flow rate increased. It is concluded that, in the dog, the
      calcium species found in stimulated juice result from a redistribution of calcium
      secreted along with proteins, whereas at low secretion rate, juice calcium level
      depends mainly on interstitial Ca++ diffusion into the main pancreatic ducts.

PMID- 8145006
TI  - Disparate cytochemical characteristics and production of cytokines and
      prostaglandin E2 by human mononuclear phagocytes from the blood, lung, and
      peritoneal cavity.
AB  - The cytochemical characteristics and the production of tumor necrosis factor
      alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and prostaglandin E2 (PGE2) by
      peritoneal macrophages were compared with those of blood monocytes and alveolar
      macrophages. The comparative percentages of mononuclear phagocytes positive for
      peroxidase were as follows: blood monocytes > peritoneal macrophages > alveolar
      macrophages. The comparative percentages of cells positive for nonspecific
      esterase were as follows: alveolar macrophages > peritoneal macrophages = blood
      monocytes. The intensity of staining for nonspecific esterase was highest in
      alveolar macrophages and lowest in blood monocytes. Constitutive release of TNF,
      IL-1 beta, and PGE2 was minimal by each cell type. Lipopolysaccharide-stimulated
      TNF production by alveolar macrophages was approximately five times greater than
      that of monocytes and 10 times greater than that of peritoneal macrophages. By
      contrast, lipopolysaccharide-stimulated blood monocytes produced significantly
      more IL-1 beta than did peritoneal or alveolar macrophages. Lipopolysaccharide
      stimulated production of PGE2 by peritoneal macrophages was significantly less
      than that of alveolar macrophages or blood monocytes. Thus peritoneal macrophages
      release relatively low levels of IL-1 beta, TNF, and PGE2 in response to
      lipopolysaccharide. Peritoneal and alveolar macrophages differ with respect to
      both cytochemical characteristics and lipopolysaccharide-stimulated production of
      TNF and PGE2 but are similar in their limited capacity to produce IL-1 beta.

PMID- 8145007
TI  - von Willebrand factor as a regulator of intrinsic factor X activation.
AB  - Factor VIII is an important cofactor in the intrinsic activation of factor X. To
      function effectively as a cofactor, factor VIII must be activated. In plasma,
      factor VIII circulates in a complex with von Willebrand factor, and although
      thrombin can activate complexed factor VIII, the activation by activated factor X
      is inhibited by von Willebrand factor. In this study, the effect of von
      Willebrand factor on the generation of factor Xa by the factor IXa-VIII complex
      was investigated. Purified human factors VIII, IXa, and X were incubated on human
      umbilical vein endothelial cells or phospholipid vesicles in the presence of
      calcium ions, and the generation of factor Xa was followed. In the presence of
      von Willebrand factor, a prolonged lag-phase and a dose-dependent inhibition of
      factor X activation was observed. These effects were not observed when von
      Willebrand factor was preincubated with a monoclonal antibody directed against
      von Willebrand factor that blocks factor VIII binding. When factor VIII was
      activated with thrombin before the incubation, neither the monoclonal antibody
      nor von Willebrand factor had an effect on the rate of factor X activation.
      Preincubation of endothelial cells with the monoclonal antibody resulted in a
      somewhat higher rate of factor X activation. When endothelial cells from a
      patient with von Willebrand's disease type I were used, preincubation of the
      monoclonal antibody had no effect on the rate of factor X activation. We conclude
      that von Willebrand factor on the surface of endothelial cells can modulate the
      intrinsic factor X activation. This effect is greatly enhanced, however, by the
      addition of exogenous von Willebrand factor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145008
TI  - Serologic methods in the laboratory diagnosis of latex rubber allergy: study of
      nonammoniated, ammoniated latex, and glove (end-product) extracts as allergen
      reagent sources.
AB  - In the absence of approved natural rubber latex skin testing reagents, serologic
      methods for the detection of latex-specific immunoglobulin E (IgE) antibody are
      useful in the definitive diagnosis of latex allergy. In this study we examined
      extracts from two nonammoniated latex (NAL), two ammoniated latex (AL), and three
      diverse latex rubber gloves as sources of allergen for their utility in solid
      phase radioimmunoassays (SPRIAs) for latex-specific IgE. Serum samples were
      collected from 46 healthcare workers (HCWs), one beautician, two clerks, and
      seven children with spina bifida who exhibited clinical evidence of latex
      associated contact dermatitis (CD, n = 8), contact urticaria (CU) with or without
      CD (n = 15), or systemic reactions involving respiratory symptoms with or without
      anaphylaxis (n = 33) and from 10 latex-exposed HCW control subjects with no latex
      allergy symptoms. Serum samples were coded and analyzed in a blinded manner in
      two laboratories by three particulate and four nonparticulate SPRIAs with
      different latex extracts on the allergosorbent. Intraassay coefficient of
      variation as assessed with 44 split, randomized, blinded serum specimens was <
      20%. Agreement within a source of latex (e.g., NAL, AL, or gloves) and between
      laboratories was > 90% concordant for Glove 1/Glove 2 and NAL1/2. Specific IgE
      antilatex was detected in one of 10 latex-exposed control serum samples by five
      of the seven SPRIAs, despite a lack of clinical evidence for latex allergy in
      this otherwise atopic individual. Latex-specific IgE was detected in the serum of
      22% of subjects with CU with or without CD, suggesting that IgE antibody may not
      be the primary factor involved in the induction of these local reactions.
      Approximately two thirds of the systemic reactor group had detectable latex
      specific IgE in their serum, with levels ranging from 0.7 to 338 ng/ml. The
      predictive characteristics of these assays will await future provocation testing.
      We conclude that glove extracts contain as complete a repertoire of allergens as
      the NAL and AL. Of the three source latex materials, NAL and glove extracts
      provided the most sensitive and greatest consistency of IgE antibody results
      between laboratories.

PMID- 8145009
TI  - Intratracheal but not intravascular interleukin-1 causes acute edematous injury
      in isolated neutrophil-perfused rat lungs through an oxygen radical-mediated
      mechanism.
AB  - Our goal was to determine whether administration of interleukin-1 (IL-1)
      intratracheally causes acute edematous injury in isolated rat lungs perfused only
      with neutrophils and physiologic buffer. We found that administration of native
      (50 ng) but not heated IL-1 intratracheally rapidly (60 minutes) increased (p <
      0.05) lung weights and lung lavage Ficoll concentrations in isolated rat lungs
      perfused only with purified human neutrophils as compared with lungs given IL-1
      intratracheally alone, lungs perfused with neutrophils alone, or untreated
      control lungs. In contrast, lung weights or lavage Ficoll concentrations did not
      increase (p > 0.05) when as much as 1 microgram of IL-1 was administered
      intravascularly with neutrophils. The mechanism of injury appeared to involve
      neutrophil-derived oxygen radicals, because acute edematous injury did not occur
      in isolated lungs given IL-1 intratracheally and then perfused with neutrophils
      previously heated at 48 degrees C for 10 minutes. The latter procedure decreased
      superoxide anion (O2-.) production but did not alter the adhesion or chemotactic
      properties of neutrophils in vitro. In parallel, incubation with IL-1 and human
      neutrophils did not lyse (as measured by chromium 51 release) cultured purified
      bovine pulmonary artery endothelial cells in vitro. Our results indicate that
      increased alveolar but not intravascular concentrations of IL-1 initiate a
      neutrophil-dependent, oxidant-mediated acute edematous lung injury.

PMID- 8145010
TI  - Identification of a murine high-proliferative-potential colony-forming cell (HPP
      CFC) capable of producing a number of megakaryocytes and replating for secondary
      HPP-CFCs in culture.
AB  - The high-proliferative-potential colony-forming cell (HPP-CFC) has been shown to
      be clearly heterogeneous. Hierarchical subpopulations can be identified by
      analyzing the kinetics of cell regeneration and the specific cellular requirement
      for cytokines. In this study, a new type of HPP-CFC, termed high-proliferative
      potential mixed colony-forming unit-megakaryocyte (HPP-mCFU-MK), was detected in
      murine bone marrow cell cultures. The HPP-mCFU-MK was able to form macroscopic
      colonies that fit the criteria of the HPP-CFC colony but contained a number of
      megakaryocytes. Its growth was stimulated by either aplastic anemia serum (AAS)
      or a combination of three or more recombinant hematopoietic growth factors but
      was not inhibited by transforming growth factor-beta 1 (TGF-beta 1) and platelet
      factor 4 (PF4) in vitro. The recloning of the 12-day-old HPP-mCFU-MK colonies
      picked up from AAS-stimulated primary cultures caused secondary formation of HPP
      CFC colonies. These data suggest that HPP-mCFC-MK is a new subset of stem cell
      characterized by its ability to produce directly a number of megakaryocytes in
      response to multifactor stimulation, to generate a secondary set of HPP-CFC in
      replating culture, and to be unaffected by TGF-beta 1 and PF4 treatment.

PMID- 8145011
TI  - Pathogenesis of pulmonary fibrosis: platelet-derived growth factor precedes
      structural alterations in the Hermansky-Pudlak syndrome.
AB  - Peptides that modulate mesenchymal cell function have been detected in the
      fibrotic lung disorders once physiologic dysfunction is present. Despite this
      close association with manifest disease, their role in initiating alveolar
      remodeling remains unknown. We examined the hypothesis that one potent peptide,
      platelet-derived growth factor (PDGF), would be present at the alveolar surface
      before the onset of physiologic dysfunction in patients in whom pulmonary
      fibrosis subsequently develops. Bronchoalveolar lavage and physiologic assessment
      were performed in asymptomatic patients with the Hermansky-Pudlak syndrome (n =
      30), obligate heterozygous (n = 9), and normal volunteers (control group). Lavage
      cell number and profile were normal, but alveolar macrophages demonstrated
      characteristic autofluorescence and ultrastructural features of ceroid. Lavage
      fluid from physiologically normal patients with Hermansky-Pudlak syndrome and
      from those with occult restrictive disease demonstrated two PDGF-related peptides
      (14 kd and 38 kd). Radioligand binding and fibroblast proliferation assay
      demonstrated that the peptides were functional. By immunoassay the concentration
      of PDGF in lavage fluid was six times greater than control values (p < 0.01). In
      situ hybridization together with bioassay indicated that alveolar macrophages
      were one cellular source of PDGF. Similar results were obtained for
      heterozygotes. These data identify macrophage-derived PDGF peptides as important
      candidate molecules in the initiation of alveolar remodeling in the fibrotic lung
      disorders.

PMID- 8145012
TI  - Rapid modification of ribosomal S6 kinase II (S6KII) in rabbit peritoneal
      neutrophils stimulated with chemotactic factor fMet-Leu-Phe.
AB  - The ribosomal S6 kinase II (S6KII) in rabbit neutrophils was studied by
      immunoblotting with antibodies prepared against recombinant S6KII. A protein with
      apparent molecular weight of 80,000 Da in SDS-gel was recognized by the
      antibodies. A shift of the apparent molecular weight to 84,000 Da in SDS-gel was
      observed in cells stimulated with the chemotactic factor fMet-Leu-Phe.
      Cytochalasin B and phorbol 12-myristate 13-acetate, but not A23187, stimulated
      both the tyrosine phosphorylation of p41mapk and the change of the mobility of
      S6KII. Pretreatment of the cells with quin 2/AM inhibited almost completely the
      tyrosine phosphorylation of p41mapk induced by fMet-Leu-Phe, but only partially
      the change in mobility of S6KII. Under various conditions, near maximum
      conversion of S6KII was observed even if only about 40% of the maximum level of
      tyrosine phosphorylation of p41mapk was achieved. The results suggest that rapid
      modification of S6KII occurs in chemotactic factor-stimulated neutrophils.
      Furthermore, the modification of S6KII induced by fMet-Leu-Phe requires either
      only partial tyrosine phosphorylation of p41mapk or the activation of kinase(s)
      other than the p41mapk isoform.

PMID- 8145013
TI  - Interleukin-10 is a potent inhibitor of tumor cytotoxicity by human monocytes and
      alveolar macrophages.
AB  - The effects of purified human interleukin-10 (IL-10) on the expression of
      antitumor activity of human monocytes and alveolar macrophages (AMs) obtained by
      centrifugal elutriation and bronchoalveolar lavage, respectively, from the same
      healthy donors were examined. Monocytes and AMs were incubated for 16 h in medium
      with lipopolysaccharide (LPS) in the presence or absence of IL-10 or IL-4, and
      then their tumoricidal activity was assayed by measuring 125I-IUdR release from
      human melanoma (A375) cells. Addition of IL-10 to cultures of monocytes or AMs
      with LPS resulted in dose-dependent suppression of their cytotoxicity against
      A375 cells, the suppression of the activity of monocytes being the higher. IL-10
      also suppressed the synergistic effects of interferon-gamma and desmethyl
      muramyldipeptide in activation of monocytes. IL-10 inhibited the early induction
      phase of monocyte activation but not the effector phase (monocyte-mediated
      cytotoxicity). IL-10 plus IL-4 inhibited the antitumor activities of AMs and
      monocytes much more than either IL-10 or IL-4 alone. IL-10 and IL-4 at suboptimal
      concentrations also showed synergistic inhibitory effects. These findings suggest
      that IL-10 may be important in vivo in down-regulating the antitumor activities
      of monocytes and AMs in the lung by inhibiting their productions of antitumor
      effector molecules.

PMID- 8145015
TI  - Chemokine expression in trinitrochlorobenzene-mediated contact hypersensitivity.
AB  - The expression of the murine IP-10 and MCP-1 genes has been examined in the skin
      of mice during contact hypersensitivity reactions to the hapten
      trinitrochlorobenezene (TNCB). In both naive and passively sensitized animals,
      challenge with TNCB resulted in elevated expression of both genes as early as 4 h
      as detected by Northern hybridization analysis. Twenty-four hours after
      challenge, expression was markedly reduced in naive animals but remained elevated
      in sensitized animals. This prolonged expression of chemokine gene products
      correlates with the tissue swelling response generally used as a measure of
      delayed-type hypersensitivity (DTH) in this model and suggests that the continued
      expression of these genes results from the stimulation of hapten-specific T
      helper cells. Examination of cell type expression patterns by in situ
      hybridization using 3H-radiolabeled riboprobes confirmed the results of Northern
      hybridization experiments. Both genes were expressed predominantly in cells
      exhibiting the morphology of connective tissue fibroblasts, although the
      distribution of cells positive for IP-10 mRNA expression differed from that of
      cells expressing MCP-1 mRNA. IP-10 expression was localized almost exclusively to
      a population of connective tissue cells surrounding the fur follicle. MCP-1
      expression was rarely found associated with fur follicles but instead was
      distributed throughout the dermis in cells embedded in the collagenous
      extracellular matrix. Surprisingly, neither endothelial cells lining the small
      vessels located deep within the dermis nor epidermal keratinocytes were positive
      under any of the conditions utilized in the present study. Expression of both IP
      10 and MCP-1 has been previously reported in a variety of distinct cell types in
      vitro. The present results indicate that only a subset of the cell types with
      such potential are stimulated to express these chemokine genes in vivo during
      hapten-mediated DTH responses, implying the presence of subtle cell type- and
      tissue-specific control mechanisms.

PMID- 8145014
TI  - Selective regulation of human neutrophil functions by the cell activation
      inhibitor CI-959.
AB  - The cell activation inhibitor CI-959 [5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol
      5-ylbenzo[ b]thiophene-2- carboxamide, monosodium salt] was evaluated for its
      effects on human neutrophil functions. CI-959 inhibited spontaneous migration and
      chemotaxis toward N-formyl-methionyl-L-leucyl-L-phenylalanine (fMLP) with 50%
      inhibition (IC50) values of 3.6 and 3.1 microM, respectively. CI-959 also
      inhibited superoxide anion generation in response to C5a, fMLP, serum-opsonized
      zymosan (SOZ), concanavalin A (Con A), and calcium ionophore A23187 with IC50
      values of 2.5, 4.7, 14.5, 5.4, and 14.8 microM, respectively. In comparison, CI
      959 inhibited myeloperoxidase microM, respectively. In comparison, CI-959
      inhibited myeloperoxidase release in response to C5a, fMLP, SOZ, and Con A with
      IC50 values of 11.6, 16.1, 7.5, and < 1.0 microM, respectively, while inhibiting
      the response to A23187 by only 5.5% at 100 microM. At concentrations up to 100
      microM, CI-959 had no effect on the respiratory burst or degranulation in
      response to L-alpha-1,2-dioctanoylglycerol (DiC8) or phorbol 12-myristate 13
      acetate (PMA). In addition, the compound inhibited leukotriene B4 release
      stimulated by fMLP and SOZ (IC50 values 4.0 and 2.5 microM, respectively), while
      having less activity against the A23187-stimulated response (IC50 > 100 microM).
      These results demonstrate that CI-959 inhibits cellular responses to stimuli that
      mobilize intracellular calcium. For cellular responses to inophore-mediated
      calcium influx, only oxygen radical production was inhibited by CI-959. CI-959
      was further evaluated for its effects on neutrophil stimulus-response coupling.
      At 100 microM, CI-959 had no effect on human neutrophil phospholipase C or
      protein kinase C. CI-959 inhibited fMLP-stimulated intracellular calcium
      mobilization and calcium influx with IC50 values of 16.7 and 3.1 microM,
      respectively, and exhibited less potent calmodulin antagonist activity (IC50 =
      90.5 microM). These results indicate that CI-959 may exert its stimulus- and
      response-specific inhibitory effects on neutrophil functions, in part, through
      inhibition of calcium-regulated signalling mechanisms.

PMID- 8145016
TI  - Slow calcium waves imaged in myeloid cells derived from neonatal cord blood.
AB  - Myeloid cells were derived from neonatal cord blood by culture with granulocyte
      macrophage colony-stimulating factor for approximately 8 days. The resultant cell
      population contained large adherent cells (diameter > or = microns), expressing
      formylated peptide receptors that were functionally coupled to cytosolic free
      Ca2+ signaling. Imaging of the cytosolic free Ca2+ changes in these cells
      revealed initial focal release of Ca2+ from a site from within the cell, with
      elevated Ca2+ also near the cell edge. Increased cytosolic free Ca2+ moved as a
      slow oscillating wave across the cell (velocity 1 microns/s). As similar events
      may occur in mature neutrophils and monocytes but be difficult to resolve because
      of the small size of these cells, it was concluded that neonatal myeloid cells
      may provide a useful model system for the investigation of Ca2+ signaling in
      myeloid cells.

PMID- 8145017
TI  - A method for obtaining and culturing large numbers of purified organ-derived
      murine endothelial cells.
AB  - Fibroblast growth factor 1 (FGF-1)-coated collagen-gelatin sponges were affixed
      to various tissues to generate vascular beds, in which the vessels originated in
      the tissue to which the sponges were affixed. Organ-derived endothelium was
      obtained from vascularized sponges implanted in or on the skin, peritoneal wall,
      abdominal mesentery, epimysium, spleen, and liver. Collagenase digestion yielded
      single-cell suspensions that were analyzed by flow cytometry. Approximately 25%
      of the cells were positive for the endothelial cell (EC) markers MECA-32 and Sca
      1 and for uptake of diIAcLDL. Similar results were obtained when sponges were
      implanted in several different mouse strains, although there was some evidence of
      heterogeneity in the degree of vascularization and EC recovery. Long-term
      cultures of high purity were obtained when the ECs were grown on mitomycin C
      treated L929 feeder layers, in medium supplemented with cis-hydroxyproline and
      FGF-1. These cells have been utilized in preliminary studies of T cell-EC
      binding. Thus we have developed a generalized method for the recovery and culture
      of organ-derived murine endothelial cells. This technique should greatly improve
      the feasibility of studies of the interactions between murine endothelial and
      immune effector cells.

PMID- 8145018
TI  - Transient expression of prostaglandin endoperoxide synthase-2 during mouse
      macrophage activation.
AB  - We investigated regulation of macrophage prostaglandin production during
      activation by interferon gamma (IFN-gamma) and lipopolysaccharide (LPS). An in
      vitro model was established using the mouse macrophage-like cell line RAW 264.7.
      Cells were cultivated in the presence of IFN-gamma and LPS for up to 48 h and
      changes in the secretion of nitric oxide (NO.) and tumor necrosis factor alpha
      (TNF-alpha) were observed as activation markers. Under these conditions a prompt
      and strong increase in PGE2 production was found in the first 8 h followed by
      nearly constant generation of PGE2 during the next 40 h. In contrast, the
      activity of prostaglandin endoperoxide synthase (PGHS), measured as PGE2
      production of microsomal protein fractions, was also increased, but reached a
      clear maximum at 24 h. Recently a second form of PGHS was cloned (PGHS-2) and
      specific antibodies and mRNA probes for both isoforms are available. PGHS-2
      enzyme was expressed maximally after 24 h of activation whereas PGHS-1 was not
      influenced. In the presence of IFN-gamma and LPS, PGHS-2 mRNA expression reached
      a maximum at 8 h but PGHS-1 mRNA was not induced during the whole time period.
      These data indicate that changes in PG synthesis following macrophage activation
      are due to regulation of PGHS-2 expression.

PMID- 8145019
TI  - Fluoride prevents degranulation of the azurophilic and specific granules in
      electropermeabilized neutrophils.
AB  - The effect of AlF4- on the degranulation process in human neutrophils was
      investigated. In intact neutrophils, AlF4- induced degranulation, whereas in
      electropermeabilized neutrophils AlF4- did not stimulate degranulation. In
      electropermeabilized neutrophils, fluoride ions proved to be inhibitory for the
      degranulation induced by addition of Ca2+ and/or GTP-gamma-S. Another phosphatase
      inhibitor, okadaic acid, inhibited degranulation induced by Ca2+ or by GTP-gamma
      S but not degranulation induced by the combination of Ca2+ plus GTP-gamma-S. It
      is concluded that under suboptimal conditions of stimulation with Ca2+ or GTP
      gamma-S, protein dephosphorylation plays an important role in the degranulation
      response in human neutrophils.

PMID- 8145020
TI  - Thymic peptide modulates glutathione redox cycle and antioxidant enzymes in
      macrophages.
AB  - The effect of a 6-kDa thymic peptide (TP) on the oxidative burst of the murine
      macrophage cell line J774 was determined. TP was incubated with J774 cells at 37
      degrees C and 5% CO2 for 18 h, oxidative burst was triggered by zymosan, and
      chemiluminescence was amplified by luminol and measured in an automated
      luminometer. TP exhibited a concentration-dependent suppression of oxidative
      burst. To study the mechanisms involved in TP's suppression of oxidative burst,
      its effect on the glutathione redox cycle and antioxidant enzymes was
      investigated. J774 cells were incubated with varying concentrations of TP for 18
      h, washed, resuspended in phosphate-buffered saline, and sonicated to obtain cell
      lysate. Biochemical assays were performed with the lysate. TP was shown to
      increase the level of glutathione, and activities of glutathione-peroxidase and
      glutathione-reductase, indicating its ability to modulate the glutathione redox
      cycle. The activity of antioxidant enzyme superoxide dismutase was enhanced
      significantly by TP treatment while catalase activity remained unaffected. These
      results suggest that TP possesses an antioxidant property and therefore may be
      involved in the regulation of free radical mediated reactions.

PMID- 8145021
TI  - Regulation of hepatic endothelial cell and macrophage proliferation and nitric
      oxide production by GM-CSF, M-CSF, and IL-1 beta following acute endotoxemia.
AB  - Treatment of rats with bacterially derived lipopolysaccharide (LPS), a condition
      that mimics acute endotoxemia, results in a significant increase in the number of
      endothelial cells and macrophages in the liver. This is correlated with the
      release of proinflammatory and cytotoxic mediators that induce liver damage. In
      the present studies, we analyzed the effects of various inflammatory mediators
      released during the pathogenesis of hepatic injury on proliferation of liver
      nonparenchymal cells. To induce acute endotoxemia female Sprague-Dawley rats were
      injected intravenously with 5 mg/kg LPS. Endothelial cells and macrophages were
      isolated 48 h later by combined collagenase and pronase perfusion of the liver
      followed by centrifugal elutriation. Interleukin-1 alpha (IL-1 alpha),
      interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) had no effect
      on proliferation of either endothelial cells or macrophages. In contrast, whereas
      interleukin-1 beta (IL-1 beta) inhibited the proliferation of endothelial cells
      from untreated rats, this cytokine stimulated the growth of cells from
      endotoxemic rats. The colony-stimulating factors, granulocyte-macrophage colony
      stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF),
      also markedly enhanced the proliferation of endothelial cells, as well as
      macrophages from endotoxemic rats. Macrophages from endotoxemic rats were more
      sensitive to the colony-stimulating factors than cells from untreated rats. In
      contrast, the inflammatory mediators LPS and interferon-gamma (IFN-gamma)
      inhibited endothelial cell and macrophage growth, an effect that was partially
      blocked in endothelial cells by the nitric oxide synthase inhibitor NG-monomethyl
      L-arginine (L-NMMA). This suggests that growth inhibition in these cells is
      mediated, in part, by nitric oxide. Interestingly, in both endothelial cells and
      macrophages from endotoxemic rats, GM-CSF, M-CSF, and IL-1 beta synergized with
      LPS and IFN-gamma to induce nitric oxide production. This was correlated with a
      further inhibition of proliferation that was partially reversed by L-NMMA in
      endothelial cells but not macrophages. Taken together these data demonstrate that
      endothelial cell and macrophage proliferation in the liver is controlled by a
      variety of mediators released during endotoxemia; however, the mechanisms
      regulating growth in the two cell types are distinct.

PMID- 8145022
TI  - Use of the 5'-flanking region of the mouse perforin gene to express human Fc
      gamma receptor I in cytotoxic T lymphocytes.
AB  - Expression of the gene encoding the cytolytic granule protein perforin is
      restricted to cytotoxic lymphocytes. To undertake a functional analysis of the
      immediate 5'-promoter region of the mouse perforin gene, we transiently
      transfected mouse perforin promoter-chloramphenicol acetyltransferase (CAT)
      reporter gene constructs into cytotoxic T, T lymphoid, B-lymphoid, and
      nonlymphoid cell lines. The transcriptional activity of the perforin promoter was
      restricted to cytotoxic lymphocytes. The perforin promoter was controlled by
      several positive (in perforin-positive cells) and negative (in perforin-negative
      cells) cis-acting regions, spread over at least 1.1 kilobases. The most specific
      expression of the CAT reporter gene in the interleukin-2-dependent cytotoxic T
      cell line CTLL-R8 was obtained with the mouse perforin promoter encompassing
      positions -1104 to +1 in relation to the RNA cap site. This construct expressed
      65- to 70-fold higher CAT activity than the promoterless CAT construct in
      perforin-expressing cells but only 1- to 5-fold higher CAT activity than the
      promoterless construct in nonlymphoid cells. On the basis of these data, we used
      this most specifically active mouse perforin promoter, -1104 to +1, to express in
      CTLL-R8, a chimeric human receptor comprising the extracellular domains of human
      Fc gamma RI and the transmembrane and intracellular domains of TCR zeta.
      Selection in G418-containing medium produced CTLL-R8 transfectant clones that (1)
      expressed high levels of human Fc gamma RI mRNA; (2) expressed cell surface Fc
      gamma RI as demonstrated by immunoprecipitation and their ability to bind the Fc
      portion of human and mouse monoclonal antibodies (mAbs) in an isotype-specific
      manner, and (3) bound RBC expressing mucin-1 (Muc-1) peptide in the presence of a
      chimeric mouse-human anti-Muc-1 mAb. Activation of CTLL-R8 transfectants upon
      engagement of the human Fc gamma RI was evidenced by their ability to lyse tumor
      target cells in an mAb isotype-dependent manner. The successful expression of a
      functional chimeric gene in CTLL-R8 suggests that the mouse perforin promoter
      represents a novel reagent for expressing exogenous genes in cytotoxic T
      lymphocytes.

PMID- 8145023
TI  - Differential RNA regulation by staphylococcal enterotoxins A and B in murine
      macrophages.
AB  - Staphylococcal enterotoxin A (SEA) is significantly better than enterotoxin B
      (SEB) in activating tumor necrosis factor (TNF) secretion by B6MP102 cells. Both
      toxins bound to B6MP102 cells; however, SEB competed less effectively with SEA
      than SEA competed with SEB. This suggested that receptors unique to SEA were
      present on B6MP102 cells. Signal transduction occurred in response to both
      toxins. Within 30 s after addition, SEA and SEB significantly increased the F
      actin concentration in B6MP102 cells. However, only SEA induced increased TNF
      mRNA levels. B6MP102 cells incubated with interferon-gamma and SEB secreted TNF.
      However, enhanced mRNA expression was delayed and the concentration of TNF
      secreted was less than that of B6MP102 cells stimulated with SEA. Although these
      data suggest that receptors unique to SEA are present on B6MP102 cells, they also
      indicate that staphylococcal enterotoxins differentially regulate TNF at the RNA
      level, perhaps because of differences in binding to the plasma membrane.

PMID- 8145024
TI  - Expression of p47-phox and p67-phox proteins in murine bone marrow-derived
      macrophages: enhancement by lipopolysaccharide and tumor necrosis factor alpha
      but not colony stimulating factor 1.
AB  - We have investigated the relationship between the expression of the p47-phox and
      p67-phox cytosolic components of the NADPH oxidase and priming of the macrophage
      respiratory burst. Western blot analysis revealed that murine bone marrow-derived
      macrophages (BMM) contain immunoreactive proteins detected by antisera raised
      against recombinant human p47-phox and p67-phox. Priming BMM by exposure to tumor
      necrosis factor alpha (TNF-alpha) or lipopolysaccharide (LPS) increased the
      levels of p47-phox and p67-phox. Colony-stimulating factor 1 (CSF-1), which we
      previously found to have a negative effect on the priming of murine macrophages,
      had no effect on the level of p47-phox but down-regulated that of p67-phox. Our
      results suggest that the regulatory effects of LPS, TNF-alpha, and CSF-1 on the
      respiratory burst of BMM may be due to modulation of the expression of the p47
      phox and p67-phox cytosolic components of the NADPH oxidase.

PMID- 8145025
TI  - Differential expression of CD43 (leukosialin, sialophorin) by mononuclear
      phagocyte populations.
AB  - CD43 is a hematopoietic cell antigen whose distribution includes T lymphocytes,
      plasma cells, neutrophils, and platelets. Although it has been detected on
      peripheral blood monocytes, its expression by other mononuclear phagocytes has
      not been well documented. Possible changes in monocyte/macrophage CD43 expression
      in response to inflammation are also poorly defined. To examine these questions,
      the expression of CD43 by rat peripheral blood monocytes and both resident and
      elicited peritoneal macrophages was examined. By flow cytometry with two anti
      CD43 monoclonal antibodies, blood monocytes were found to express large amounts
      of surface CD43, whereas surface CD43 expression by resident peritoneal
      macrophages was negligible. Peritoneal macrophage populations elicited by
      intraperitoneal injection of thioglycollate were uniformly positive for surface
      CD43, although the level of expression was lower than that found on monocytes. By
      labeling resident macrophages with a fluorescent tracer dye, this phenotypic
      shift was found to reflect an influx of CD43-positive elicited macrophages
      coupled with a disappearance of CD43-negative resident cells. Evidence from both
      flow cytometry and Western blotting studies suggests that the CD43 expressed by
      elicited peritoneal macrophages is less heavily sialylated than that expressed by
      blood monocytes. These findings, coupled with recent evidence that CD43
      influences cellular adhesion, indicate that differential expression of CD43 may
      play a role in monocyte/macrophage trafficking.

PMID- 8145026
TI  - HIV-1 envelope protein gp120 affects phenotype and function of monocytes in
      vitro.
AB  - We investigated the effect of human immunodeficiency virus type 1 (HIV-1)
      recombinant gp120 (rec.gp120) on phenotype and function of cultured monocytes.
      Rec.gp120 significantly reduced the accessory function of monocytes to stimulate
      autologous lymphocytes with anti-CD3, the Fc receptor-mediated chemiluminescence
      of monocytes, and the expression of CD4 and Fc receptor I/II, while the
      expression of the monocyte marker CD14 and major histocompatibility complex class
      I and II was not influenced. According to these phenotypic results, preincubation
      of monocytes with rec.gp120 depressed anti-CD3 antibody-induced T cell
      stimulation and Fc receptor-mediated phagocytosis as determined by
      chemiluminescence. Interferon-gamma release of lymphocytes induced by purified
      protein derivative of tuberculin was enhanced by gp120. These effects of isolated
      gp120 on monocyte immune functions in vitro might contribute to the understanding
      of the pathophysiology of HIV-1 infection in vivo.

PMID- 8145027
TI  - Metastatic competence of BW5147 T-lymphoma cell lines is correlated with in vitro
      invasiveness, motility and F-actin content.
AB  - The aim of our study was to investigate whether the level of actin polymerization
      plays a role in the motile and tissue infiltrating behavior of malignant lymphoma
      cells. For a panel of cell lines derived from the murine BW5147 T-cell lymphoma,
      we had previously shown a correlation between experimental metastasis formation
      and in vitro monolayer invasion. We have analyzed the motility and the F-actin
      content of six nonmetastatic, noninvasive (meta-inv-) and five metastatic,
      invasive (meta+inv+) variants of BW5147. Fourier analysis of cell contours was
      used to quantify shape changes of cells. All meta+inv+ lines rapidly protruded
      and retracted pseudopodia, whereas only one of the six meta-inv- lines showed
      this type of motility. Flow cytometry of cells stained with fluorescein-labeled
      phalloidin showed that the motile meta+inv+ cell lines have a higher F-actin
      content than their nonmotile meta-inv- counterparts. The results indicate that in
      lymphoma cells a high level of actin polymerization is a prerequisite for the
      formation of pseudopodia, which in turn are necessary for infiltration of the
      cells into tissues, and eventually for efficient metastasis formation. A
      corollary of this conclusion is that regulation of actin polymerization is a
      possible target for intervention aimed at moderating the spread of malignant
      lymphoma.

PMID- 8145028
TI  - Bifurcation analysis pf periodic SEIR and SIR epidemic models.
AB  - The bifurcations of the periodic solutions of SEIR and SIR epidemic models with
      sinusoidally varying contact rate are investigated. The analysis is carried out
      with respect to two parameters: the mean value and the degree of seasonality of
      the contact rate. The corresponding portraits in the two-parameter space are
      obtained by means of a numerical continuation method. Codimension two
      bifurcations (degenerate flips and cusps) are detected, and multiple stable modes
      of behavior are identified in various regions of the parameter space. Finally, it
      is shown how the parametric portrait of the SEIR model tends to that of the SIR
      model when the latent period tends to zero.

PMID- 8145029
TI  - On some formulas in a partnership model from the perspective of a semi-Markov
      process.
AB  - Many deterministic models of sexually transmitted diseases, as well as population
      models in general, contain elements of stochastic or statistical reasoning. An
      example of such a model is that of Dietz and Hadeler (1988) concerning sexually
      transmitted diseases in which there is partnership formation and dissolution.
      Among the interesting formulas in this paper, which enter into the analysis of
      the model, are those for the expected number of partners a male or female has
      during a lifetime. To a probabilist such formulas suggest the possibility that
      some stochastic process may be constructed so as to yield these formulas as well
      as others that may be of interest. The principal purpose of this paper is to
      demonstrate that such a stochastic process does indeed exist in the form of a
      three state semi-Markov process in continuous time with stationary laws of
      evolution and with a one-step density matrix determined by four parameters which
      were interpreted as constant latent risk functions in the classical theory of
      competing risks. This construction of a semi-Markov process not only provides a
      framework for the systematic derivation of the formulas of Dietz and Hadeler but
      also suggests pathways for extensions to the age-dependent case.

PMID- 8145030
TI  - Anguilliform body dynamics: a continuum model for the interaction between muscle
      activation and body curvature.
AB  - A two dimensional continuum model for the body mechanics of the lamprey is
      derived from a simple discrete rod and pivot structure. Each element in the
      discrete structure consists of two smoothly jointed light rods with perpendicular
      extensions at each of the midpoints between which is fixed a quasi muscle
      segment. The muscle segment is attributed with the viscous and elastic properties
      of all the animal tissue plus the ability to produce force. The travelling wave
      of muscle activation in the real animal is modelled by a corresponding time
      dependent forcing term at each segment. A linearisation of the ensuing continuum
      model, corresponding to low curvature dynamics, is investigated. The profiles
      obtained compare favourably with those of a lamprey moving out of water on a
      smooth surface. In addition the phase difference at each point on the body
      between the wave of muscle activation and the mechanical wave observed on the
      body indicates that the mechanical wave progresses slower than, but at the same
      frequency as, the wave of activation; this is a property that is also observed in
      the freely swimming lamprey.

PMID- 8145031
TI  - Autoimmunity and apoptosis.

PMID- 8145032
TI  - The V beta complementarity determining region 1 of a major histocompatibility
      complex (MHC) class I-restricted T cell receptor is involved in the recognition
      of peptide/MHC I and superantigen/MHC II complex.
AB  - We investigated the role of the complementarity determining region 1 (CDR1) of T
      cell receptor (TCR) beta chain both in antigen/major histocompatibility complex I
      (MHC I) and in superantigen (SAg)/MHC II complex recognition. Residues 26 to 31
      of the V beta 10 domain of a TCR derived from an H-2Kd-restricted cytotoxic clone
      were individually changed to alanine, using site-directed mutagenesis, and the
      mutated TCR beta chains were transfected along with the wild-type TCR alpha chain
      into a TCR alpha-beta-T hydridoma. These mutations affected antigen/H-2Kd complex
      recognition, although to a different extent, as estimated by interleukin 2
      production. Certain mutations also affected differently the recognition of two
      Staphylococcal toxins, exfoliative toxin and Staphylococcal enterotoxin C2,
      presented by HLA-DR1. Whereas mutation of residues D30 or T31 affect the
      recognition of both toxins, residues T26, L27, and H29 are critical for the
      recognition of only one of the SAgs. These observations demonstrate the
      participation of the CDR1 region in the recognition of peptide/MHC class I as
      well as SAg/MHC II complexes.

PMID- 8145033
TI  - Efficient presentation of soluble antigen by cultured human dendritic cells is
      maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4
      and downregulated by tumor necrosis factor alpha.
AB  - Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4
      we have established dendritic cell (DC) lines from blood mononuclear cells that
      maintain the antigen capturing and processing capacity characteristic of immature
      dendritic cells in vivo. These cells have typical dendritic morphology, express
      high levels of major histocompatibility complex (MHC) class I and class II
      molecules, CD1, Fc gamma RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured
      DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable
      of triggering cord blood naive T cells. Most strikingly, these DCs are as
      efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to
      specific T cell clones. Their efficiency of antigen presentation can be further
      enhanced by specific antibodies via FcR-mediated antigen uptake. Incubation of
      these cultured DCs with tumor necrosis factor alpha (TNF-alpha) or soluble CD40
      ligand (CD40L) for 24 h results in an increased surface expression of MHC class I
      and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9
      splice variant (CD44-v9); by contrast, Fc gamma RII is markedly and sometimes
      completely downregulated. The functional consequences of the short contact with
      TNF-alpha are in increased T cell stimulatory capacity in MLR, but a 10-fold
      decrease in presentation of soluble TT and a 100-fold decrease in presentation of
      TT-immunoglobulin G complexes.

PMID- 8145034
TI  - Turnover of naive- and memory-phenotype T cells.
AB  - On the basis of their surface markers, T lymphocytes are divided into subsets of
      "naive" and "memory cells". We have defined the interrelationship and relative
      life spans of naive and memory T cells by examining the surface markers on murine
      T cells incorporating bromodeoxyuridine, a DNA precursor, given in the drinking
      water. Three findings are reported. First, using a new method we show that the
      release of newly formed naive T cells from the unmanipulated thymus is very low
      (confirming the findings of others with surgical approaches). Second, in
      thymectomized mice, T cells with a naive phenotype remain in interphase for
      prolonged periods; however, some of these cells divide and retain (or regain)
      their "naive" markers. Third, most T cells with a memory phenotype divide
      rapidly, but others remain in interphase for many weeks. Collectively, the data
      indicate that long-lived T cells have multiple phenotypes and contain a mixture
      of memory cells, naive (virgin) cells, and memory cells masquerading as naive
      cells.

PMID- 8145035
TI  - p56lck interacts via its src homology 2 domain with the ZAP-70 kinase.
AB  - p56lck, a member of the src family of protein tyrosine kinases, is an essential
      component in T cell receptor (TCR) signal transduction. p56lck contains a src
      homology 2 (SH2) domain found in a number of proteins involved in intracellular
      signaling. SH2 domains have been implicated in protein-protein interactions by
      binding to sequences in target proteins containing phosphorylated tyrosine. Using
      an in vitro assay, we have studied specific binding of tyrosine-phosphorylated
      proteins to a recombinant p56lck SH2 domain. In nonactivated Jurkat cells, two
      tyrosine-phosphorylated proteins were detected. Stimulation with anti-CD3
      monoclonal antibodies induced the binding of seven additional tyrosine
      phosphorylated proteins to the SH2 domain of p56lck. We have identified the zeta
      associated tyrosine kinase, ZAP-70, as one of these proteins. Evidence suggests
      that binding of ZAP-70 to p56lck SH2 is direct and not mediated by zeta. The
      significance of this interaction was further investigated in vivo. p56lck could
      be coprecipitated with the zeta/ZAP-70 complex and conversely, ZAP-70 was
      detected in p56lck immunoprecipitates of activated Jurkat cells. The physical
      association of p56lck and ZAP-70 during activation supports the recently proposed
      functional cooperation of these two tyrosine kinases in TCR signaling.

PMID- 8145036
TI  - Functionally active Epstein-Barr virus-transformed follicular dendritic cell-like
      cell lines.
AB  - Follicular dendritic cells (FDC) are unique nonlymphoid cells found only in
      germinal centers. FDC can be distinguished from other accessory cells based on a
      characteristic set of cell surface markers. It is known that FDC are able to
      rescue germinal center B cells from apoptosis. To investigate the role of FDC in
      the process of selection and maturation of B cells during germinal center
      reactions, we tried to establish factor-independent immortalized FDC-like cell
      lines. Because freshly isolated FDC express the Epstein-Barr Virus (EBV) receptor
      CD21, we attempted EBV transformation on isolated FDC. After incubation of FDC
      enriched cell populations with EBV, cell lines were obtained consisting of slowly
      duplicating very large cells. These cell lines have a fibroblast-like morphology
      but could be clearly distinguished from several human fibroblast cell lines by
      displaying a different phenotype including intercellular adhesion molecule 1,
      CD40, and CD75 expression. Detection of the EBV-encoded proteins latent membrane
      protein 1 and Epstein-Barr virus nuclear antigen 2 in our FDC-like cell lines
      implicated successful EBV transformation. FDC-like cells are able to bind
      nonautologous B cells and preserve the latter from apoptosis. The binding of B
      cells to FDC-like cells is dependent on adhesion via lymphocyte function
      associated antigen 1/intercellular adhesion molecule 1 and closely resembles the
      pattern of emperipolesis as described by others. These data demonstrate that FDC
      can be successfully infected by EBV, and that the cell lines obtained share
      phenotypic and functional characteristics with freshly isolated FDC.

PMID- 8145037
TI  - A human tumor necrosis factor (TNF) alpha mutant that binds exclusively to the
      p55 TNF receptor produces toxicity in the baboon.
AB  - A number of recent studies have demonstrated that cellular responses to tumor
      necrosis factor (TNF) mediated by the p55 and the p75 TNF receptors are distinct.
      To evaluate the relative in vivo toxicities of wild-type TNF alpha (wtTNF alpha)
      and a novel p55 TNF selective receptor agonist, healthy, anesthetized baboons
      (Papio sp.) were infused with a near-lethal dose of either wtTNF alpha or a TNF
      alpha double mutant (dmTNF alpha) that binds specifically to the p55, but not to
      the p75, TNF receptor. Both wtTNF alpha and dmTNF alpha produced comparable acute
      hypotension, tachycardia, increased plasma lactate, and organ dysfunction in
      Papio. However, administration of wtTNF alpha produced a marked granulocytosis
      and loss of granulocyte TNF receptors, whereas little if any changes in
      neutrophil number or cell surface TNF receptor density were seen after dmTNF
      alpha mutant administration. Infusion of dmTNF alpha resulted in a plasma
      endogenous TNF alpha response that peaked after 90-120 min. We conclude that
      selective p55 TNF receptor activation is associated with early hemodynamic
      changes and the autocrine release of endogenous TNF alpha. Significant systemic
      toxicity results from p55 TNF receptor activation, but the role of the p75 TNF
      receptor in systemic TNF toxicity requires further study.

PMID- 8145038
TI  - Polymorphic Hh genes in the HLA-B(C) region control natural killer cell frequency
      and activity.
AB  - We demonstrated earlier that individuals homozygous for conserved major
      histocompatibility complex (MHC)-extended haplotypes have low natural killer (NK)
      activity as measured by cytolysis of the K562 tumor cell lines. In the present
      study, we investigated the segregation and MHC linkage of NK activity in families
      in which MHC haplotypes of human histocompatibility leukocyte antigens (HLA)-A, 
      C, and -B, complotype, and DR specificities are known. In two informative
      families, low activity was inherited as a recessive trait linked to the MHC. By
      using individuals homozygous for specific fragments of extended haplotypes or for
      HLA-B alleles, we found that the HLA-C and -B and not the complotype or HLA-DR
      region contains genes controlling NK activity. The majority of the unrelated
      individuals with low NK activity were homozygous or doubly heterozygous for HLA
      B7 (Cw7), B8 (Cw7), B44 (Cw5), B18, or B57 (Cw6). Thus, these alleles form one
      complementation group designated NKB1. Another less frequent group, NKB2, was
      also identified, and consisted of individuals homozygous for B35 (Cw4). NK
      activity was correlated with the number of circulating NK (CD16+ CD56+) cells.
      Individuals homozygous for the NKB complementation groups have fewer circulating
      NK cells than individuals heterozygous for these alleles and alleles of other
      complementation groups, possibly explaining the low activity of cells in these
      subjects. These findings suggest that during the maturation of NK cells there is
      NK cellular deletion in donors homozygous for NKB genes resulting in low NK cell
      numbers and activity.

PMID- 8145039
TI  - Granulocyte/macrophage colony-stimulating factor stimulates the expression of the
      5-lipoxygenase-activating protein (FLAP) in human neutrophils.
AB  - The synthesis of leukotrienes in human blood neutrophils chiefly relies on the
      activity of two enzymes, phospholipase A2 and 5-lipoxygenase (5-LO). In turn, the
      activation of the 5-LO requires the participation of a recently characterized
      membrane-bound protein, the 5-LO-activating protein (FLAP). In this study, we
      have investigated conditions under which FLAP expression in neutrophils may be
      modulated. Of several cytokines tested, only granulocyte/macrophage colony
      stimulating factor (GM-CSF) (and to a lesser extent tumor necrosis factor alpha)
      significantly increased expression of FLAP. GM-CSF increased FLAP mRNA steady
      state levels in a time- and dose-dependent manner. The stimulatory effect of GM
      CSF on FLAP mRNA was inhibited by prior treatment of the cells with the
      transcription inhibitor, actinomycin D, and pretreatment of the cells with the
      protein synthesis inhibitor, cycloheximide, failed to prevent the increase in
      FLAP mRNA induced by GM-CSF. The accumulation of newly synthesized FLAP, as
      determined by immunoprecipitation after incorporation of 35S-labeled amino acids,
      was also increased after incubation of neutrophils with GM-CSF. In addition, the
      total level of FLAP protein was increased in GM-CSF-treated neutrophils, as
      determined by two-dimensional gel electrophoresis, followed by Western blot. GM
      CSF did not alter the stability of the FLAP protein, indicating that the effect
      of GM-CSF on FLAP accumulation was the consequence of increased de novo synthesis
      as opposed to decreased degradation of FLAP. Finally, incubation of neutrophils
      with the synthetic glucocorticoid dexamethasone directly stimulated the
      upregulation of FLAP mRNA and protein, and enhanced the effect of GM-CSF. Taken
      together, these data demonstrate that FLAP expression may be upmodulated after
      appropriate stimulation of neutrophils. The increase in FLAP expression induced
      by GM-CSF in inflammatory conditions could confer upon neutrophils a prolonged
      capacity to synthesize leukotrienes.

PMID- 8145040
TI  - Human CD4 restores normal T cell development and function in mice deficient in
      murine CD4.
AB  - The ability of a human coreceptor to function in mice was investigated by
      generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient
      (mCD4-/-) background. From developing thymocyte to matured T lymphocyte
      functions, hCD4 was shown to be physiologically active. By examining the
      expansion and deletion of specific V beta T cell families in mutated mice with
      and without hCD4, it was found that hCD4 can participate in positive and negative
      selection. Mature hCD4 single positive cells also were found in the periphery and
      they were shown to restore MHC class II-restricted alloreactive and antigen
      specific T cell responses that were deficient in the mCD4 (-/-) mice. In
      addition, these hCD4 reconstituted mice can generate a secondary immunoglobulin G
      humoral response matching that of mCD4 wild-type mice. The fact that human CD4 is
      functional in mice and can be studied in the absence of murine CD4 should
      facilitate studies of human CD4 activity in general and human immunodeficiency
      virus 1 gp120-mediated pathogenesis in acquired immune deficiency syndrome
      specifically.

PMID- 8145041
TI  - Initiation of autoimmunity to the p53 tumor suppressor protein by complexes of
      p53 and SV40 large T antigen.
AB  - Antinuclear antibodies (ANAs) reactive with a limited spectrum of nuclear
      antigens are characteristic of systemic lupus erythematosus (SLE) and other
      collagen vascular diseases, and are also associated with certain viral
      infections. The factors that initiate ANA production and determine ANA
      specificity are not well understood. In this study, high titer ANAs specific for
      the p53 tumor suppressor protein were induced in mice immunized with purified
      complexes of murine p53 and the Simian virus 40 large T antigen (SVT), but not in
      mice immunized with either protein separately. The autoantibodies to p53 in these
      mice were primarily of the IgG1 isotype, were not cross-reactive with SVT, and
      were produced at titers up to 1:25,000, without the appearance of other
      autoantibodies. The high levels of autoantibodies to p53 in mice immunized with
      p53/SVT complexes were transient, but low levels of the autoantibodies persisted.
      The latter may have been maintained by self antigen, since the anti-p53, but not
      the SVT, response in these mice could be boosted by immunizing with murine p53.
      Thus, once autoimmunity to p53 was established by immunizing with p53/SVT
      complexes, it could be maintained without a requirement for SVT. These data may
      be explained in at least two ways. First, altered antigen processing resulting
      from the formation of p53/SVT complexes might activate autoreactive T helper
      cells specific for cryptic epitopes of murine p53, driving anti-p53 autoantibody
      production. Alternatively, SVT-responsive T cells may provide intermolecular
      intrastructural help to B cells specific for murine p53. In a second stage, these
      activated B cells might themselves process self p53, generating p53-responsive
      autoreactive T cells. The induction of autoantibodies during the course of an
      immune response directed against this naturally occurring complex of self and
      nonself antigens may be relevant to the generation of specific autoantibodies in
      viral infections, and may also have implications for understanding the
      pathogenesis of ANAs in SLE. In particular, our results imply that autoimmunity
      can be initiated by a "hit and run" mechanism in which the binding of a viral
      antigen to a self protein triggers an immune response that subsequently can be
      perpetuated by self antigen.

PMID- 8145042
TI  - Elimination of interleukin 6 attenuates coagulation activation in experimental
      endotoxemia in chimpanzees.
AB  - The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is
      controversial. To assess the part of IL-6 in inflammatory responses to endotoxin,
      we investigated eight chimpanzees after either a bolus intravenous injection of
      Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin
      with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n =
      4). Anti-IL-6 did not affect the induction of the cytokine network (tumor
      necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by
      endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and
      neutrophil degranulation, as monitored by the measurement of elastase-alpha 1
      antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin
      induced activation of coagulation, monitored with the plasma levels of the
      prothrombin fragment F1+2 and thrombin-antithrombin III complexes, whereas
      activation of fibrinolysis, determined with the plasma concentrations of plasmin
      alpha 2-antiplasmin complexes, remained unaltered. We conclude that IL-6 does not
      have a feedback effect on the release of other cytokines after injection of
      endotoxin, and that it is not involved in endotoxin-induced neutrophilia or
      neutrophil degranulation. IL-6 is, however, an important intermediate factor in
      activation of coagulation in low grade endotoxemia in chimpanzees.

PMID- 8145044
TI  - Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response
      at mucosal surfaces.
AB  - Immunohistochemical analysis of challenge sites such as skin and the peritoneal
      cavity has identified neutrophils as virtually the sole cellular participants in
      acute bacterial inflammation, peak influx occurring 24-48 h in advance of
      mononuclear cell populations associated with adaptive immunity. This study
      challenges the general applicability of this paradigm. We demonstrate here that
      the earliest detectable cellular response after inhalation of Moraxella
      catarrhalis organisms is the recruitment of putative class II major
      histocompatibility complex-bearing dendritic cell (DC) precursors into the airway
      epithelium, the initial wave arriving in advance of the neutrophil influx. Unlike
      the neutrophils which rapidly transit into the airway lumen, the DC precursors
      remain within the epithelium during the acute inflammatory response where they
      differentiate, and develop the dendriform morphology typical of resident DC found
      in the normal epithelium. During the ensuing 48-h period, these cells then
      migrate to the regional lymph nodes. No comparable DC response was observed after
      epidermal or intraperitoneal challenge, and it may be that mucosal surfaces are
      unique in their requirement for rapid DC responses during acute inflammation. We
      hypothesize that the role of the DC influx during acute inflammation may be
      surveillance for opportunistic viruses, and that this covert protective mechanism
      is operative at a restricted number of mucosal tissue sites.

PMID- 8145043
TI  - Longitudinal analysis of T cell receptor (TCR) gene usage by human
      immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals
      a limited TCR repertoire.
AB  - Human immunodeficiency virus 1 (HIV-1) infection is associated with a vigorous
      cellular immune response that allows detection of cytotoxic T lymphocyte (CTL)
      activity using freshly isolated peripheral blood mononuclear cells (PBMC).
      Although restricting class I antigens and epitopes recognized by HIV-1-specific
      CTL have been defined, the effector cells mediating this vigorous response have
      been characterized less well. Specifically, no studies have addressed the breadth
      and duration of response to a defined epitope. In the present study, a
      longitudinal analysis of T cell receptor (TCR) gene usage by CTL clones was
      performed in a seropositive person using TCR gene sequences as a means of
      tracking responses to a well-defined epitope in the glycoprotein 41 transmembrane
      protein. 10 CTL clones specific for this human histocompatibility leukocyte
      antigen-B14-restricted epitope were isolated at multiple time points over a 31-mo
      period. All clones were derived from a single asymptomatic HIV-1-infected
      individual with a vigorous response to this epitope that was detectable using
      unstimulated PBMC. Polymerase chain reaction amplification using V alpha and V
      beta family-specific primers was performed on each clone, followed by DNA
      sequencing of the V-D-J regions. All 10 clones utilized V alpha 14 and V beta 4
      genes. Sequence analysis of the TCR revealed the first nine clones isolated to
      also be identical at the nucleotide level. The TCR-alpha junctional region
      sequence of the tenth clone was identical to the junctional region sequences of
      the other nine, but this clone utilized distinct D beta and J beta gene segments.
      This study provides evidence that the observed high degree of HIV-1-specific CTL
      activity may be due to monoclonal or oligoclonal expansion of specific effector
      cells, and that progeny of a particular CTL clone may persist for prolonged
      periods in vivo in the presence of a chronic productive viral infection. The
      observed limited TCR diversity against an immunodominant epitope may limit
      recognition of virus variants with mutations in regions interacting with the TCR,
      thereby facilitating immune escape.

PMID- 8145045
TI  - Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and
      oncostatin M are growth factors for human myeloma cell lines using the
      interleukin 6 signal transducer gp130.
AB  - Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in
      human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL),
      whose growth is completely dependent on addition of exogenous IL-6, can be
      obtained reproducibly from every patient with terminal disease. Four cytokines,
      ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and
      oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL
      6 and share numerous biological activities with this IL. We found that these four
      cytokines stimulated proliferation and supported the long-term growth of two out
      of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal
      proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2
      ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml),
      but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The
      growth-promoting effect of these four cytokines was abrogated by anti-gp130
      antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies.
      No detectable changes in the morphology and phenotype were found when myeloma
      cells were cultured with one of these four cytokines instead of IL-6. Concordant
      with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and
      gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only
      in the two HMCL responsive to LIF and OM.

PMID- 8145046
TI  - Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the
      proliferation of human plasmacytoma cells via the common signal transducer,
      gp130.
AB  - We analyzed the stimulatory effect of oncostatin M (OSM), leukemia inhibitory
      factor (LIF), interleukin 6 (IL-6), IL-11, and the inhibitory effect of anti-IL-6
      antibody (Ab), anti-IL-6 receptor monoclonal antibody (mAb), and anti-gp130 mAb
      on the growth of human plasmacytoma cells freshly isolated from a patient with
      multiple myeloma. The purified cells showed a plasmacytoid morphology and
      expressed CD38, CD54, and CD56 antigens but no CD3, CD5, CD10, CD19, CD20, or
      very late antigen 5. IL-6 receptor (IL-6R) and its signal transducer, gp130, were
      expressed on their cell surface at a low level. Dose-dependent proliferation of
      the cells in response to OSM, LIF, and IL-6, but not to IL-11, was observed using
      [3H]TdR incorporation in vitro. Both anti-IL-6 Ab and anti-IL-6R mAb inhibited
      the growth of the cells in the presence or absence of exogenous IL-6. These cells
      release IL-6 but not OSM or LIF into the culture supernatant during short-term
      culture. Therefore, an autocrine growth mechanism mediated by IL-6, but not by
      OSM or LIF, was confirmed. Furthermore, anti-gp130 mAb completely inhibited the
      proliferation of the cells induced by OSM, LIF, as well as IL-6. These data
      indicate that OSM, LIF, and IL-6 can act as growth factors of human plasmacytoma
      cells through a common signal transducer, gp130, on their cell surface, and also
      suggest the potential therapeutic application of anti-gp130 mAb, as well as anti
      IL-6R mAb against myeloma/plasmacytomas.

PMID- 8145047
TI  - Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not
      dependent on IL-4 from non-Th cells.
AB  - Interleukin 4 (IL-4) is essential for the induction of immunoglobulin E (IgE)
      responses in mice. Recent in vitro studies have suggested that IL-4 derived from
      non T helper (Th) cells, in particular from mast cells and basophils, may be
      essential for triggering of IL-4 expression in Th cells and may directly
      contribute to IgE isotype switch induction. Here, we have generated mice carrying
      a functional IL-4 gene only in Th cells or non-Th cells, respectively, by
      reconstitution of IL-4-deficient mice (IL-4T mice) with CD4+ or CD4- spleen cells
      from congenic wild-type animals. In mice in which only CD4+ cells are able to
      express IL-4, antigen-specific IgE is produced in a T cell-dependent immune
      response. Thus, induction of IL-4 expression in Th cells can occur in the absence
      of IL-4 from non-Th cells, which suggests that at least some Th cells can express
      IL-4 in response to another signal which has yet to be identified. No IgE is
      detectable, however, in mice in which only CD4- cells can express IL-4,
      suggesting that Th cells are the primary, if not the only source of IL-4 for
      initial induction of IgE synthesis.

PMID- 8145048
TI  - Two waves of recombinase gene expression in developing thymocytes.
AB  - During T cell development in the thymus, T cell receptor (TCR) alpha, beta,
      gamma, and delta genes are rearranged and expressed. TCR rearrangement strictly
      depends upon the coordinate activity of two recombinase activating genes, Rag-1
      and Rag-2. In this study we have followed the expression of these genes at
      different stages of intrathymic development. The results indicate that there are
      two periods of high Rag-1 and Rag-2 mRNA expression. The first wave peaks early
      at the CD25+CD4-CD8-CD3- stage of development and coincides with the initial
      appearance of transcripts derived from fully rearranged TCR beta, gamma, and
      delta genes, whereas the second wave occurs later at the CD4+CD8+ stage
      coincident with full-length TCR alpha mRNA expression. Active downregulation of
      Rag-1 and Rag-2 mRNA expression appears to occur in vivo between the two peaks of
      recombinase activity. This phenomenon can be mimicked in vitro in response to
      artificial stimuli such as phorbol myristate acetate and calcium ionophore.
      Collectively our data suggest that recombinase expression is actively regulated
      during early thymus development independently of cell surface expression of a
      mature heterodimeric TCR protein complex.

PMID- 8145049
TI  - Constitutive expression of interferon gamma-inducible protein 10 in lymphoid
      organs and inducible expression in T cells and thymocytes.
AB  - Interferon gamma-inducible protein 10 (IP-10), a member of a family of small
      proinflammatory chemotactic polypeptides, is expressed in interferon gamma
      stimulated keratinocytes, macrophages, fibroblasts, and endothelial cells. Here
      we report that IP-10 is also expressed by activated but not resting T hybridoma
      cells, normal T cells, and thymocytes. Although resting lymphocytes did not
      synthesize IP-10, surprisingly high levels of IP-10 transcripts were found in
      lymphoid organs (spleen, thymus, and lymph nodes). Thymic and splenic stromal
      cells were found to express constitutively high levels of both IP-10 mRNA and
      protein, accounting for the high level of spontaneous expression in lymphoid
      tissue. Therefore, in addition to its role as a proinflammatory cytokine, IP-10
      may participate in T cell effector function and perhaps T cell development.

PMID- 8145050
TI  - Production of interleukin 10 by islet cells accelerates immune-mediated
      destruction of beta cells in nonobese diabetic mice.
AB  - The T helper type 2 (Th2) cell product interleukin 10 (IL-10) inhibits the
      proliferation and function of Th1 lymphocytes and macrophages (M phi). The
      nonobese diabetic mouse strain (NOD/Shi) develops a M phi and T cell-dependent
      autoimmune diabetes that closely resembles human insulin-dependent diabetes
      mellitus (IDDM). The objective of the present study was to explore the
      consequences of localized production of IL-10 on diabetes development in NOD/Shi
      mice. Surprisingly, local production of IL-10 accelerated the onset and increased
      the prevalence of diabetes, since diabetes developed at 5-10 wk of age in 92% of
      IL-10 positive I-A beta g7/g7, I-E- mice in first (N2) and second (N3) generation
      backcrosses between IL-10 transgenic BALB/c mice and (NOD/Shi) mice. None of the
      IL-10 negative major histocompatibility complex-identical littermates were
      diabetic at this age. Furthermore, diabetes developed in 33% of I-A beta g7/d, I
      E+ N3 mice in the presence of IL-10 before the mice were 10 wk old. Our findings
      support the notion that IL-10 should not simply be regarded as an
      immunoinhibitory cytokine, since it possesses powerful, immunostimulatory
      properties as well. Furthermore, our observations suggest that beta cell
      destruction in NOD mice may be a Th2-mediated event.

PMID- 8145051
TI  - CDw60: a marker for human CD8+ T helper cells.
AB  - The existence of helper cells among the CD8+ T cell subset has been recognized
      for a long time. However, the phenotype of these cells has remained elusive. In
      this study, we provide evidence that the expression of the CDw60 antigen on human
      CD8+ T cell allows one to distinguish between CD8+ T helper cells and CD8+ T
      cells with cytotoxic and suppressor capacity. CDw60 monoclonal antibodies (mAb)
      recognize the 9-O-acetylated disialosyl group on ganglioside GD3 expressed on 20
      40% of CD8+ cells. By use of the direct and indirect mAb-rosetting technique, we
      were able to isolate the CDw60+CD8+ and CDw60-CD8+ cells at high purity. The
      alloantigen-specific cytotoxic activity of CD8+ cells resided entirely in the
      CDw60- population. Helper and suppressor capacity of both CD8 subsets was assayed
      by the pokeweed mitogen-induced differentiation of B cells into immunoglobulin
      secreting cells. These studies clearly indicate that the CDw60+CD8+ subset
      provided substantial help to B lymphocytes, whereas the CD8+ cells with the CDw60
      phenotype were suppressing B cell differentiation. Both subsets produced similar
      amounts of interleukin 2 (IL-2) after stimulation with phytohemagglutinin.
      Activation with phorbol myristate acetate in combination with Ca-ionophore
      induced IL-4 secretion in both populations, but preferentially in the CDw60+
      subset, whereas the vast majority of interferon gamma was produced by the CDw60
      CD8+ cells. When used in combination with other markers, CDw60 may prove to be
      useful in defining CD8+ subsets with reciprocal functional activities.

PMID- 8145052
TI  - The heat-stable antigen can alter very late antigen 4-mediated adhesion.
AB  - The integrin very late antigen, (VLA-4) alpha 4 beta 1 and its counter receptor
      vascular cell adhesion molecule 1 (VCAM-1) are involved in B cell maturation and
      pre-B cell attachment to bone marrow stroma cells. We have analyzed whether heat
      stable antigen (HSA), a marker for immature leukocytes, is involved in such cell
      adhesion phenomena. HSA is a glycolipid-anchored, highly glycosylated surface
      protein differentially expressed on cells during the maturation of both the
      hematopoietic and nervous systems. We found that pre-B cells lacking HSA (due to
      targeted disruption of both alleles) can still bind via VLA-4 to tumor necrosis
      factor alpha-stimulated endothelioma cells. This binding, however, cannot be
      blocked by an anti-VCAM-1 antibody. Restoration of HSA expression restores the
      inhibitable VCAM-1 binding. We also found that pre-B cells lacking HSA did not
      bind to the FN40 fragment of fibronectin but reexpression of HSA restored VLA-4
      mediated binding to fibronectin. Thus, expression of HSA on pre-B cells modifies
      the binding specificity of VLA-4 for two known ligands.

PMID- 8145053
TI  - Induction of hapten-specific tolerance by interleukin 10 in vivo.
AB  - Interleukin 10 (IL-10) is released during the induction phase of contact
      sensitivity and was shown in prior functional studies to convert epidermal
      Langerhans cells (LC) from potent inducers of primary immune responses to
      specifically tolerizing cells in vitro. To investigate whether IL-10 also
      subserves the function of a tolerizing agent in vivo ears of BALB/c or C3H mice
      were injected intradermally with 1-2 micrograms of recombinant mouse (rm)IL-10 8
      h before epicutaneous application of 3% trinitrochlorobenzene (TNCB; a contact
      allergen). As a control, mice were injected with phosphate-buffered saline or IL
      10 plus neutralizing amounts of anti-IL-10 mAb. 5 d later, mice were challenged
      with 1% TNCB on contralateral ears and ear swelling response was measured 24 h
      later. Whereas control-treated mice showed a normal ear swelling response to
      epicutaneous challenge (delta mm-2 = 25 +/- 5), ear swelling response of IL-10
      treated animals was significantly inhibited (delta mm-2 = 3 +/- 2). Coinjection
      of IL-10-specific mAb together with rmIL-10 completely abrogated this effect. To
      differentiate between a state of nonresponsiveness and induction of tolerance by
      IL-10, mice initially treated with IL-10 and TNCB were resensitized with 3% TNCB
      in the absence of any treatment after 14 d of rest (group 1). Again mice were
      challenged 5 d later and ear swelling responses were tested. Whereas control mice
      treated with allergen alone (group 2) showed a good swelling response (delta mm-2
      = 28 +/- 6), IL-10-treated mice (group 1) showed a minimal response towards
      application of allergen (delta mm-2 = 4 +/- 2). To show that anergy induction by
      IL-10 was antigen-specific, mice initially treated with IL-10 plus TNCB were
      exposed to 0.5% dinitrofluorobenzene (DNFB) 14 d later (group 1). After challenge
      with 0.1% DNFB, IL-10-treated mice showed an ear swelling response (delta mm-2 =
      13 +/- 3; group 1) similar to that of control mice only sensitized with DNFB
      (delta mm-2 = 14 +/- 3; group 3). In an attempt to show the induction of antigen
      specific tolerance in these mice in vitro, regional lymph nodes of mice initially
      treated with TNCB plus IL-10 (group 1) and control-treated mice (groups 2 and 3)
      were prepared and cultured in the presence of TNBS, dinitrobenzene sulfonate
      (DNBS), or medium to measure antigen-specific proliferation.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8145054
TI  - Characterization and chemosensitivity of two cell lines derived from human
      glioblastomas.
AB  - We have characterized two human glioblastoma cell lines, which were designated as
      YH cells and AM cells. The two cell lines maintained morphological appearance
      observed in the primary culture and immunohistochemically expressed glial
      fibrillary acidic protein (GFAP) and S-100 protein. Population doubling time for
      YH cells and AM cells indicated 30 hours and 25 hours, respectively, in an
      exponential phase of culture. Inoculation of AM cells into athymic nude mice
      formed large tumors at a high incidence. As with chemosensitivity to
      chloroethylnitrosourea, O6-methylguanine-DNA methyltransferase (MGMT) activity
      was measured in in vitro cultured cells as well as tumor specimens obtained at
      surgery. YH cells showed a high MGMT activity of 1196 fmol/mg and drug resistance
      to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea
      hydrochloride (ACNU) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) assay. YH tumor specimens indicated an MGMT activity of 301
      fmol/mg, which reflected poor effectiveness of ACNU chemotherapy in the clinical
      evaluation. AM cells had an extremely low MGMT activity of 16 fmol/mg and were
      vulnerable to ACNU. Original tumor specimens of AM cells however expressed a high
      value of 628 fmol/mg. Considering that ACNU chemotherapy was not effective in the
      both patients, an MGMT activity of original tumors related with responsiveness to
      ACNU. Discrepancy in an MGMT activity between the in vitro cell lines and the
      respective tumor specimens comes from selection of ACNU-sensitive cells or
      alteration in biological characteristics during long term culture. These results
      suggest that cell lines derived human brain tumors are useful targets for
      understanding the chemosensitivity of human malignant gliomas and for
      establishing a pertinent chemosensitivity test.

PMID- 8145055
TI  - Metallothionein and anticancer agents: the role of metallothionein in cancer
      chemotherapy.
AB  - Metallothioneins (MTs) are intracellular proteins containing the highest amount
      of thiol groups within the cytoplasm. These thiol groups are able to bind several
      cytotoxic agents, such as platinum compounds and alkylating agents. Increased
      levels of MT are one mechanism of resistance to these anticancer drugs, as
      intracytoplasmic binding of MT prevents the active molecules from reaching their
      target, the intranuclear DNA of tumor cells. MT synthesis can easily be induced
      by physiologic heavy metals such as zinc and copper. Pharmacological modulation
      of MT levels has been used to increase the MT pool in normal tissues and decrease
      their susceptibility to the toxicity of anticancer drugs. In the case of tumors
      arising in the brain, where the inducibility of MT synthesis is low, this
      approach would allow protection of normal tissues without decreasing the
      antitumor activity of the cytotoxic agents. The interaction of MT with cytotoxic
      agents is not limited to covalent binding. A correlation between MT synthesis and
      amplification of oncogenes such as ras has been reported. Furthermore, the
      cytotoxic drugs are bound by MT after competition with zinc and copper; these
      metals are cofactors of numerous metalloenzymes, some of which are involved in
      the metabolism of nucleic acids. Competitive displacement of these metals might
      modify nucleic acid metabolism and influence cellular proliferation. On the other
      hand, increased MT levels could provide a zinc cofactor reserve that increases
      the cell's reparative potential when faced by DNA damage by cytotoxic
      agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145056
TI  - Multiple fraction-per-day radiotherapy for patients with brain stem tumors.
AB  - Brain stem tumors are among the most resistant brain tumors to therapy. The
      majority progress within 18 months of diagnosis and treatment. Multiple-fraction
      per-day (MFD) radiotherapy would theoretically allow higher total doses of
      radiotherapy to be delivered in order to improve local tumor control without
      increasing neurotoxicity secondary to treatment. Seventeen patients with brain
      stem tumors were evaluated and treated at Duke University Medical Center (DUMC)
      from 1985 to 1991 with a MFD regimen. Six patients were accrued to Pediatric
      Oncology Group (POG) Protocol 8495 and were not included in this analysis,
      leaving eleven patients for review. Local fields were treated with fraction sizes
      of 110 or 117 cGy twice daily. There were 3 patients who received a total of 60.5
      68.2 Gy and 8 who received 70.2-71.5 Gy. Initial and follow-up CT and/or MRI
      studies were available for review on all but one patient. All patients had
      progression of disease and have died. Median time to tumor progression was 5.8
      months. Median overall survival was 11.2 months. There was no significant
      influence upon time to tumor progression or survival by total radiation dose
      received. Patients were classified by imaging group per the criteria of Stroink
      et al. based on review of their pre-treatment CT or MRI scans. One patient had no
      initial films available, 2 were in Group II (no contrast was given to separate A
      or B), 3 in IIA, 4 in IIB, and 1 in III. Autopsy in 3 patients failed to
      demonstrate histologic evidence of injury attributable to radiotherapy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8145058
TI  - Hypophyseal non-Hodgkin's lymphoma presenting with clinical panhypopituitarism
      successfully treated with chemotherapy.
AB  - A patient is described with a testicular Non-Hodgkin's Lymphoma (NHL) presenting
      with panhypopituitarism caused by a hypophyseal localization. A 67Gallium
      scintigraphy showed avid uptake in the hypophyseal region. Obviously 67Gallium
      could reach the tumor, by the intravenous route, which was the reason to treat
      the patient with intravenous chemotherapy. A complete remission was induced,
      which seems to be lasting (+25 months). As far as we know this is the first
      report of panhypopituitarism caused by a hypophyseal NHL in the hypophysis and
      successfully treated by intravenous chemotherapy.

PMID- 8145059
TI  - Frontal oligo-astrocytoma with orbito-ethmoidal involvement.

PMID- 8145057
TI  - Gangliogliomas: a clinicopathological study of 25 cases and review of the
      literature.
AB  - The histopathological, clinical, and radiological findings in 25 patients (median
      age 20.5 years; range 1.7-64.2 years) with gangliogliomas were assessed to
      correlate degree of astrocytic anaplasia and proliferative potential with
      recurrence or survival. Most patients (64%) presented with seizures (median
      Karnofsky Performance Score 90%; range 70-100%). Computerized tomography and
      magnetic resonance imaging showed nonspecific abnormalities. Neoplastic ganglion
      cells were defined as heterotopic, irregularly grouped, or having more than one
      nucleus of bizarre shape or size. The astrocytic component was moderately
      anaplastic in 15 cases and highly anaplastic (HAA) in 10. Eight patients had
      gross total resection, 11 had subtotal resection, and six underwent biopsy. Ten
      patients (five gross total resection, three subtotal resection, two biopsy) had
      no further treatment, 15 underwent external irradiation, and five had adjuvant
      chemotherapy. Twenty-four patients are alive 15-394 weeks (median 203.5 weeks)
      postoperatively; one with ganglioglioma-HAA died at 65 weeks. No tumor recurred
      after gross total resection. Duration of preoperative symptoms < 1 year, greater
      anaplasia, and age > 30 years at diagnosis may have increased the risk of
      recurrence after subtotal resection or biopsy by four, three, and two times,
      respectively (not significant). Bromodeoxyuridine labeling index (BUdR LI) was <
      1% in eight non-recurring tumors and 1.3% in another recurring twice (second
      recurrence LI = 1.6%). Most patients with ganglioglioma have a good prognosis.
      After gross total resection, only observation is required. After subtotal
      resection or biopsy, recurrence is possible. BUdR labeling may guide further
      therapy.

PMID- 8145060
TI  - Interstitial brachytherapy and hyperthermia for malignant gliomas.

PMID- 8145061
TI  - Glioblastoma revisited: do clinical observations match basic science theory?
      Radiosurgery: clinical observations.

PMID- 8145062
TI  - Factors influencing tumor cell traffic in the central nervous system.

PMID- 8145063
TI  - Suppression of 9L gliosarcoma growth by copper depletion with copper-deficient
      diet and D-penicillamine.
AB  - Trace element such as Cu and Zn have important chemical and biological
      properties. Recently, tissue Cu and Zn concentrations have been correlated with
      prognosis in selected malignancies. In addition, depletion of trace metals has
      suppressive effects on tumor growth in experimental rat models. We measured
      tissue levels of Cu and Zn and investigated the inhibitory effects on tumor
      growth in a rat brain tumor model by the Cu-depletion. 9L gliosarcoma cells were
      injected subcutaneously in 24 anesthetized 5 week old male Fischer-344 rats.
      Control animals (n = 12) were given a normal diet throughout the experiment and
      hypocupremic rats (n = 12) were given a Cu-deficient diet beginning 3 weeks
      before and after tumor implantation, and administered 2 mg of D-Penicillamine
      peri os., once daily, 3 days before and after implantation. At the time of
      sacrifice, samples were taken to measure tumor weights. To determine tissue Cu
      and Zn levels, atomic absorption spectrophotometry was used. Cu, Zn and Cu/Zn
      ratio were significantly higher in control tumors than brain tissues. Cu levels
      and Cu/Zn ratio were significantly lower in hypocupremic tumors than those in
      control tumors. Zn levels in hypocupremic tumors were significantly higher than
      control tumors. Our study indicated that Cu depletion by a Cu-deficient and D
      Penicillamine reduced Cu concentration and Cu/Zn ratio in a tumor model with
      reduction of tumor weight. A metabolic approach that restricts Cu to alter the
      microenvironment within the cell must become a new horizon of cancer therapy.

PMID- 8145065
TI  - Cornelia Kennedy (1881-1969).

PMID- 8145064
TI  - Partial characterization of glioma-derived growth factor 2: a novel mitogenic
      activity from human cell line D-54 MG.
AB  - We have shown that several human malignant glioma cell lines are stimulated by
      bacterial lipopolysaccharide (E. coli 0111:B4, 1 microgram/ml) to produce a high
      molecular weight (> 200 kD) growth activity for BALB 3T3, clone A31 cells. This
      glioma-derived growth factor (GDGF-2) acts like a 'competence' factor. Malignant
      glioma cell line D-54 MG constitutively produced GDGF-2, which we have partially
      characterized from serum-free conditioned culture medium. GDGF-2 is resistant to
      heat (100 degrees C, 5 min), acidic (pH 2, 2 hr) or reducing (0.5 M 2 ME, 30 min)
      conditions as well as exposure to RNases; however, it is sensitive to > 4 freeze
      thaw cycles, alkaline (pH 11, 2 hr) conditions or pre-treatment with proteolytic
      enzymes. GDGF-2 had a pl of 6.8 determined by preparative isoelectric focusing,
      bound to DEAE, with elution at 35 and 185 mM NaCl and at 43% acetonitrile from a
      C4 reversed phase column. GDGF-2 activity was not neutralized by antibodies to
      TGF alpha, TGF beta, PDGF, VEGF or TNF alpha indicating that it is not
      immunochemically related to these growth factors. However GDGF-2 co
      chromatographed on Superose 12 HPLC (250 x 9 mm; 5% isopropanol, 6 mM CHAPS in
      PBS) with a substance that suppressed growth of mink lung epithelial cells
      (Mv1Lu), but not BALB 3T3 cells, and could be neutralized by anti-TGF beta
      antibodies. GDGF-2 activity eluted from heparin columns in 0.6 M NaCl; thus, it
      is not a heparin binding growth factor. D-54 MG cell line produced alpha 2
      macroglobulin (alpha 2M), which is known to bind TGF beta; however,
      immunoprecipitation of alpha 2M did not deplete TGF beta or GDGF-2 activity.
      Further, neither GDGF-2 or TGF beta can be dissociated into lower molecular
      weight active components by chromatography in high salt (2 M NaCl) or 2-ME (0.5
      M). GDGF-2 may be a novel autocrine or paracrine mitogen, stimulating mitotic
      division or interfering with normal cell growth regulation.

PMID- 8145066
TI  - The use of transgenic mice in nutrition research.
AB  - The ability to generate transgenic mice that express exogenous genes, express
      genes in a tissue specific manner, or do not express an endogenous gene will
      dramatically impact nutritional studies. Use of transgenic animals will greatly
      expand the types of experiments that can be performed, for example, by permitting
      researchers to examine specific mechanisms underlying nutritional relationships.
      These studies can be viewed from two perspectives; the effect of nutrition in
      general or nutrients in specific on the regulation of gene expression; and
      conversely, the effects of gene expression upon nutrient utilization or other
      aspects of metabolism. In addition, transgenic animal models have been and can be
      established to characterize human pathologies, e.g., pituitary gigantism or
      atherosclerosis, and the roles and interactions of nutrition in these and other
      metabolic diseases may then be evaluated. The use of transgenic animals in
      nutrition research is new and quite fertile, and exciting results will continue
      to surface.

PMID- 8145067
TI  - Dietary gamma-linolenic acid-enriched oil reduces body fat content and induces
      liver enzyme activities relating to fatty acid beta-oxidation in rats.
AB  - The objectives of this study were to examine the effects of dietary gamma
      linolenic acid-enriched oil extracted from fungi on rat body composition and on
      the various enzyme activities relating to fat metabolism in the liver. The oil
      contained 25.3 g gamma-linolenic acid/100 g fatty acids. The levels of gamma
      linolenic acid-enriched oil in the diets were 0, 1.5 and 4%, to give 0, 2.88 and
      7.68 g gamma-linolenic acid/kg diet. The control diet contained 8% soybean oil.
      The rats were given free access to these diets for 4 wk. Body weight gain was
      less in the gamma-linolenic acid oil-fed groups than in the control group,
      although food intake was similar among the three groups. Absolute and relative
      carcass fat weights were significantly lower in the gamma-linolenic acid oil-fed
      groups than in the control group. Carcass protein and water contents were not
      different among the three groups, although values were slightly greater than
      controls in gamma-linolenic acid-fed groups when expressed relative to body
      weight. Plasma total cholesterol and free fatty acid concentrations generally
      were lower in the gamma-linolenic acid oil-fed groups than in the control group.
      In the liver, there were no significant differences in activities of malic enzyme
      and citrate cleavage enzyme among the three groups. However, the activities of
      carnitine palmitoyl-transferase and peroxisomal beta-oxidation were significantly
      higher in the gamma-linolenic acid oil-fed groups than in the control group.
      These results clearly demonstrate that dietary gamma-linolenic acid oil reduces
      body fat content and facilitates fatty acid beta-oxidation in the liver.

PMID- 8145068
TI  - Nucleotide-free diet impairs T-helper cell functions in antibody production in
      response to T-dependent antigens in normal C57B1/6 mice.
AB  - We have previously shown that polynucleotides enhance in vitro antibody
      production in response to T-dependent antigens. This study examines the
      importance of dietary nucleotides on in vivo antibody production in response to
      antigen stimuli. C57Bl/6 mice fed a nucleotide-free diet for more than 3 wk
      demonstrated significantly lower antibody production to T-dependent antigens both
      in vivo and in vitro compared with control mice fed a nonpurified diet. Numbers
      of immunoglobulin M and G secreting cells in the spleen were also lower in mice
      fed a nucleotide-free diet after the challenge of T-dependent antigens compared
      to the controls. Responses to T-independent antigens remained intact in mice fed
      a nucleotide-free diet. T-helper cells from mice fed a nucleotide-free diet were
      less capable of inducing T-dependent antibody production in vitro compared with
      those from mice fed a nonpurified diet. Intraperitoneal injection of a
      mononucleotide-nucleoside mixture restored T-helper cell functions and T
      dependent antibody production in mice fed a nucleotide-free diet. These results
      may indicate the importance of dietary nucleotides in maintaining optimal T
      helper cell functions for humoral immune responses in response to T-dependent
      antigens.

PMID- 8145069
TI  - Protein kinase C activity is reduced in epidermal cells from energy-restricted
      SENCAR mice.
AB  - Female SENCAR mice were pre-fed a control or 40% energy-restricted (ER) diet with
      energy removed from fat and carbohydrate, or a control, balanced high fat (BHF,
      with similar energy from fat and carbohydrate), 35% energy restricted from fat
      (HCR) or 35% energy restricted from carbohydrate (HFR) diet. Epidermal cells were
      isolated by trypsin digestion for measurement of protein kinase C (PKC) activity,
      lipid composition or lipid metabolism. Dietary restriction of fat or carbohydrate
      energy (HFR or HCR group) reduced particulate PKC activity in epidermal cells
      compared with cells from control mice. The ratio of soluble particulate PKC
      activity was higher in epidermal cells from mice fed the HCR diet compared with
      those fed the HFR diet. Diet did not affect soluble PKC activity. Inositol
      accumulation was measured in the water- or lipid-soluble fractions of prelabeled
      ([3H]inositol) epidermal cells following a 1-h incubation in media with LiCl.
      Phosphatidylinositol, inositol biphosphate and inositol triphosphate fractions
      were more heavily labeled in cells from mice fed the ER diet. Energy restriction
      did not modify epidermal total lipid or phospholipid composition, but 1,2
      diacylglycerol levels were elevated in relation to cell number in epidermal cells
      from mice fed the ER diet. These data suggest that dietary energy restriction
      modified PKC activity through a pathway other than alteration in membrane lipid
      composition or inositol lipid metabolism.

PMID- 8145070
TI  - Transcriptional control of rat hepatic glutaminase expression by dietary protein
      level and starvation.
AB  - Mammalian liver possesses a unique isozyme of phosphate-activated glutaminase
      that is subject to long-term regulation. In rats during starvation or after
      consumption of diets containing high amounts of protein (60%), hepatic
      glutaminase activity was 100% higher than in rats fed a 20% protein diet.
      Conversely, rats fed low protein diets (0 and 5%) had lower hepatic glutaminase
      activity when compared with rats fed the 20% protein diet. Differences in
      activity with different dietary protein levels were not due to differences in the
      amount of food consumed. The relative abundance of mRNA encoding hepatic
      glutaminase was lower in rats fed 0% protein and higher in those starved or fed
      60% protein diet when compared with rats fed the 20% protein diet. The mRNA
      elongation assay in hepatic nuclei isolated from these animals demonstrated that
      the rate of transcription of the glutaminase gene was also different in rats
      starved or fed different levels of dietary protein. Overall, the results indicate
      that differences in hepatic glutaminase activity in rats starved or fed different
      levels of protein are mainly due to differences in the rate of transcription of
      the gene. In this way the regulation of hepatic glutaminase expression is similar
      to that seen for other enzymes involved in hepatic amino acid catabolism but
      differs markedly from that of renal glutaminase, in which changes in
      transcription rate are not observed and alterations of mRNA turnover are the
      principle mechanism of long-term regulation.

PMID- 8145071
TI  - Macronutrient regulation of lipoprotein lipase is posttranslational.
AB  - To examine the relative impact of diet and meal composition on lipoprotein lipase
      (LPL), high fat (60% of energy) (HF) and high carbohydrate (68%) (HC) diets were
      fed to Sprague-Dawley rats for 2-3 wk, followed by overnight food deprivation and
      a meal of the same composition. Heparin-releasable LPL activities, mass and mRNA
      were measured in heart, diaphragm and soleus muscle and epididymal fat after food
      deprivation and 1, 2, 4 and 8 h postprandially. No effect of dietary
      macronutrient composition on LPL activity, protein or mRNA in food-deprived rats
      was demonstrated. However, in cardiac and diaphragm muscle, heparin-releasable
      LPL activity was suppressed by HC but stimulated by HF meal-feeding at 4 h.
      Moreover, in adipose tissue, the HC meal increased LPL activity at 1, 2 and 4 h
      relative to the basal period. Although there were no consistent effects of meal
      composition on LPL mass or mRNA in any one tissue, overall LPL mass was generally
      increased by HC meal-feeding. Because there were meal composition-dependent
      differences in LPL activity but no detectable differences in mass or mRNA in a
      particular tissue, LPL regulation by meals seems to be predominantly
      posttranslational.

PMID- 8145072
TI  - Daily variation in plasma zinc concentrations in women fed meals at six-hour
      intervals.
AB  - Ten pre-menopausal women participated in two studies to measure the daily
      variations in plasma zinc when meals were fed at 6-h intervals and to determine
      if the response was related to shifts in serum insulin, glucose, calcium, or
      phosphorus concentrations. In Study 1, identical meals were fed at 6-h intervals
      for 2 d, and blood was sampled 8 times between each meal. In Study 2, the women
      fasted from 1800 h on d 1 to noon the next day, and blood was sampled hourly from
      0700-1200 on d 2. The postprandial plasma zinc response was similar following all
      four meals and accounted for 50% of the total within subject variation in plasma
      zinc. A small (2-6%) increase occurred within the first 60 min; then plasma zinc
      declined to a low point at 4 h after the meal. This characteristic pattern was
      not observed during the fasting study. Serum phosphorus varied consistently after
      each meal with a net efflux from circulation that preceded an efflux of zinc by 2
      h. The postprandial response of serum glucose and insulin were related to the
      postprandial plasma zinc response measured 6 h earlier; the variables were not
      correlated at concurrent time points. The data show that food intake is a
      determinant of the daily variations in plasma zinc. The net efflux of zinc from
      circulation following meals may reflect hepatic zinc uptake in association with
      an increase in postprandial liver metabolism.

PMID- 8145073
TI  - Dietary carbohydrates modify azoxymethane-induced intestinal carcinogenesis in
      rats.
AB  - The effect of different dietary carbohydrates (sucrose, cornstarch and high
      amylose cornstarch) on intestinal carcinogenesis was studied in male Sprague
      Dawley rats treated subcutaneously with azoxymethane (AOM) at a weekly dose of 8
      mg/kg body wt for 8 wk. The diets, high in fat and low in calcium and fiber, were
      fed during and after AOM treatment. The number of colonic adenomas per rat in the
      groups fed either starch was lower (P < 0.05) than the number in the sucrose-fed
      rats [1.06 +/- 0.38, 0.30 +/- 0.10 and 0.41 +/- 0.22 (mean +/- SEM), in the
      sucrose-, cornstarch- and high amylose cornstarch-fed groups, respectively]. The
      incidence of total intestinal tumors (adenomas + adenocarcinomas) was not
      affected by dietary treatment. However, the incidence of tumors in the small
      intestine of the rats fed the two cornstarch diets tended to be slightly lower
      than for rats fed the sucrose diet (P = 0.075). Adenoma dysplasia and
      adenocarcinoma differentiation were similar among the rats fed the three diets.
      However, the adenocarcinomas in the rats fed the cornstarch diet were
      significantly smaller than those in the rats fed sucrose [0.99 +/- 0.14 cm2 (n =
      13), 0.56 +/- 0.14 cm2 (n = 13) and 0.55 +/- 0.17 cm2 (n = 9) in rats fed the
      sucrose, cornstarch and high amylose starch diets, respectively]. Moreover, in
      the rats fed the cornstarch diet, the adenocarcinomas showed lower invasive
      potential than those in rats fed the sucrose diet. The results suggest an overall
      inhibition of AOM-induced carcinogenesis in rats fed the cornstarch diets.

PMID- 8145074
TI  - Corticotropin-releasing hormone decreases feeding, oxygen consumption and
      activity of genetically obese (ob/ob) and lean mice.
AB  - Acute effects of intracerebroventricularly administered corticotropin-releasing
      hormone (CRH) on deprivation-induced food intake, whole-body oxygen consumption,
      brown adipose tissue metabolism, and several locomotive behaviors were examined
      in 6- to 7-wk-old female genetically obese (ob/ob) and lean mice. Corticotropin
      releasing hormone depressed food intake in a dose-dependent manner, with a
      tendency for greater suppression of intake in intact ob/ob mice than in lean
      mice. Adrenalectomy abolished this tendency for CRH to be more potent in ob/ob
      mice than in lean mice. Corticotropin-releasing hormone also lowered the oxygen
      consumption of ob/ob and lean mice, without affecting brown adipose tissue
      metabolism as assessed by measurement of GDP binding to brown adipose tissue
      mitochondria. Grooming activity was lowered in CRH-injected mice. The CRH-induced
      lowering of oxygen consumption and grooming activity in mice contrasts with CRH
      induced elevations of oxygen consumption and grooming in rats, suggesting species
      specific responses to this peptide. Because effects of CRH were similar in
      adrenalectomized ob/ob and lean mice, it is unlikely that obesity-producing
      abnormalities in ob/ob mice are related to abnormal CRH action mechanisms.
      However, potential abnormalities in CRH synthesis and/or release cannot be
      excluded.

PMID- 8145076
TI  - Dietary polydextrose affects the large intestine in rats.
AB  - We compared the effects of dietary polydextrose with those of dietary fibers on
      the luminal pH and morphology of the large intestine in rats. In Experiment 1,
      animals were fed diets supplemented with two levels (5 and 10 g/100 g) of
      polydextrose or dietary fiber (cellulose or galactomannan derivatives) for 52 d.
      Polydextrose and galactomannan derivatives significantly lowered large intestinal
      pH and increased the cecal weight and surface area compared with cellulose.
      However, the thickness of the cecal muscular layer was significantly less in the
      polydextrose-fed groups than in the cellulose-fed groups. In Experiment 2, rats
      were fed either a fiber-free diet or a diet containing 5, 10 or 20 g/100 g
      polydextrose for 92 d. Dietary polydextrose significantly acidified the cecal
      contents and promoted cecal mucosal growth but thinned the cecal muscular layer.
      The shape of colonic mucosa of the group fed the 20 g/100 g polydextrose diet was
      clearly different from that of the group fed the fiber-free diet. These findings
      indicate that the effect of polydextrose on the morphology of the large intestine
      is different from the effect of dietary fibers.

PMID- 8145075
TI  - Role of dietary propionic acid and bile acid excretion in the hypocholesterolemic
      effects of oligosaccharides in rats.
AB  - The aim of this study was to evaluate the influence of dietary propionic acid and
      bile acid excretion on the hypocholesterolemic effect of fibers. For this
      purpose, rats were adapted to a diet containing 10 g inulin, 10 g beta
      cyclodextrin, or 2.5 g calcium propionate per 100 g diet. Both the inulin and
      beta-cyclodextrin diets elicited high propionic acid fermentations in the cecum
      (approximately 45% of total short-chain fatty acids) with relatively low molar
      proportions of acetic and butyric acids. In rats fed the three experimental
      diets, 5-7 mumol/min of propionic acid was absorbed in the portal vein, and
      propionic acid was entirely metabolized by the liver. Plasma cholesterol was more
      effectively depressed by the beta-cyclodextrin diet than by the inulin diet; the
      propionic acid-supplemented diet was ineffective in this respect. The inulin diet
      slightly increased fecal bile acid excretion, compared with the control diet,
      whereas beta-cyclodextrin markedly enhanced (1.8-fold) bile acid excretion.
      Microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity was slightly
      depressed in rats fed the propionic acid-supplemented diet, whereas it was
      enhanced by the beta-cyclodextrin diet in parallel to the activity of cholesterol
      7 alpha-hydroxylase. The present data suggest that absorption and further hepatic
      metabolism of large amounts of propionic acid are not sufficient to counteract
      the induction of HMG-CoA reductase resulting from bile acid fecal losses. The
      rise of these losses plays a major role in the hypocholesterolemic effect of beta
      cyclodextrin.

PMID- 8145077
TI  - True exogenous and endogenous nitrogen fractions in the human jejunum after
      ingestion of small amounts of 15N-labeled casein.
AB  - The purpose of this work was to determine exogenous and endogenous contributions
      to the overall nitrogen flux in the upper jejunum in humans. After the ingestion
      of water or 8 g of [15N]casein, the behavior of gastro-jejunal nitrogen and
      electrolyte (Na+, K+, Cl-) movements were studied in seven volunteers using the
      "slow marker" perfusion technique. The jejunal flow-rate of the chyme peaked
      during 0-20 min and 20-40 min periods following water and casein ingestion,
      respectively. Osmolarity, Cl- and Na+ concentrations decreased significantly (P <
      0.05) during the first 20 min following meal ingestion and returned to the basal
      levels in the 20-60 min period. The gastric half-emptying times (min) of the
      liquid phase differed significantly (P < 0.05) for water (7.9 +/- 0.4) and casein
      (21.4 +/- 9.1). The basal flow rate of endogenous nitrogen was 9 +/- 3.3 mmol/h
      in the jejunum. After casein ingestion, the total nitrogen content reached
      maximum values in the 20-40 min period and then progressively returned to the
      initial level. The gastro-jejunal casein absorption was 58% and the remaining
      amount of casein in the jejunum was degraded more than 80% to alcohol-soluble
      compounds. After the ingestion of a low amount of casein no significant increase
      in the endogenous nitrogen fraction was observed. The 15N-dilution technique is
      an appropriate method in humans for the direct measurement of endogenous and
      exogenous contributions to the intestinal nitrogen fraction.

PMID- 8145078
TI  - Dietary and ruminally derived trans-18:1 fatty acids alter bovine milk lipids.
AB  - The objectives of this study were to determine whether dietary fish oil enhances
      production of trans-18:1 isomers in the bovine rumen and whether flow of
      ruminally derived and/or dietary trans-18:1 to the small intestine is correlated
      with milk fat production. Four lactating Holstein cows with cannulas in the rumen
      and proximal duodenum were fed diets with 0% supplemental fat (control diet), 3%
      hydrogenated tallow fatty acids (HTFA diet), 1.5% menhaden oil plus 1.5% stearic
      acid (MO+SA diet), or 1.5% soybean oil plus 1.5% partially hydrogenated soybean
      oil (SBO+HSBO diet) in a 4 x 4 Latin square design. Intakes of trans-18:1 were 0,
      12, 0 and 69 g/d when cows were fed the control, HTFA, MO+SA and SBO+HSBO diets,
      respectively. However, the extent of 18:1 + 18:2(n-6) + 18: 3(n-3)
      biohydrogenation in the rumen was reduced by consumption of the MO+SA and
      SBO+HSBO diets. As a result, flow of trans-18:1 to the duodenum was 163 g/d for
      MO+SA-fed cows and 152 g/d for SBO+HSBO-fed cows compared with 38 g/d for cows
      fed the HTFA and control diets. Incomplete biohydrogenation accounted for all of
      the trans-18:1 flow when the MO+SA diet was fed. Compared with results when the
      HTFA and control diets were fed, milk fat percentage was lower and concentration
      of trans-18:1 in milk fat was higher when the MO+SA and SBO+HSBO diets were fed.
      Across all treatments, milk fat percentage decreased linearly with the amount of
      trans-18:1 flowing to the duodenum and the concentration of trans-18:1 in milk
      fat. Results indicate that bovine milk fat percentage is depressed by trans-18:1,
      whether derived from the diet or from incomplete biohydrogenation of unsaturated
      fatty acids.

PMID- 8145079
TI  - Dietary soybean oil changes lipolytic rate and composition of fatty acids in
      plasma membranes of ovine adipocytes.
AB  - A study was conducted to determine which fatty acids in plasma membranes of
      adipose tissue from ruminants are changed when the diet is supplemented with
      unsaturated fatty acids and to determine the effect of the fat supplement on
      adipocyte metabolism. Ten sheep were randomly assigned to two isonitrogenous
      diets containing either no added fat (control) or 5 g soybean oil/100 g diet.
      Perirenal fat was removed at slaughter, adipocytes isolated by collagenase
      digestion, and plasma membranes prepared by centrifugation on a Percoll gradient.
      Feeding soybean oil to the sheep increased (P < 0.05) linoleic acid [18: 2(n-6)]
      concentration in subcutaneous fat and isolated adipocytes, suggesting partial
      escape of dietary unsaturated fatty acids from ruminal biohydrogenation. Soybean
      oil consumption also decreased (P < 0.05) concentrations of myristic acid,
      arachidonic acid [20: 4(n-6)] and anteiso 17:0 in plasma membranes, but increased
      (P < 0.05) trans 18:1. Lipogenesis was not affected by diet, but lipolysis tended
      to be greater (P = 0.07) in sheep fed the soybean oil-containing diet than in
      those fed the control diet. In ruminants, fatty acids of ruminal origin, namely
      trans intermediates of biohydrogenation or branched-chain fatty acids of
      microbial lipid, may account for as much change in the composition of plasma
      membranes and in cellular metabolism as do the small quantities of unsaturated
      fatty acids in the diet that escape biohydrogenation.

PMID- 8145080
TI  - Tissue vitamin E status is compromised by dietary protein insufficiency in young
      growing rats.
AB  - In vitro erythrocyte hemolysis previously has been found to be significantly
      elevated in rats fed a low protein diet. To investigate the effects of dietary
      protein insufficiency on tissue vitamin E status, four groups of male weanling
      Long-Evans rats were given free access to either an 8% (wt/wt) lactalbumin diet
      containing 50 (L50) or 500 (L500) mg/kg diet of all-rac-alpha-tocopheryl acetate,
      or a 20% (wt/wt) lactalbumin diet containing 50 (N50) or 500 (N500) mg/kg of all
      rac-alpha-tocopheryl acetate for 6 wk. A fifth group (P50) was pair-fed to the
      L50 group with the N50 diet. The L50 and L500 groups showed signs of protein
      malnutrition such as growth retardation as well as lower hematocrit and plasma
      protein and albumin concentrations. The alpha-tocopherol concentrations of
      plasma, heart, lung, kidney and muscle were significantly lower in the L50 group
      compared with the N50 group. The L500 group showed significantly less alpha
      tocopherol in heart, kidney, muscle, brain and adipose tissue compared with the
      N500 group. The alpha-tocopherol concentrations in liver, testis, spleen and
      adrenal gland did not significantly differ either between the L50 and N50 groups
      or between the L500 and N500 groups. Supplementation with 500 mg/kg diet of all
      rac-alpha-tocopheryl acetate resulted in significantly higher tissue alpha
      tocopherol concentration in all tissues except muscle. The tissue alpha
      tocopherol concentrations of the P50 group were not significantly different from
      those of the N50 group. The results indicated that protein insufficiency resulted
      in significantly lower alpha-tocopherol concentrations in most tissues in young
      growing rats.

PMID- 8145081
TI  - Inositol phosphates inhibit uptake and transport of iron and zinc by a human
      intestinal cell line.
AB  - To examine the influence of inositol phosphates on the uptake and absorption of
      Fe and Zn, Caco-2 cells were grown on either plastic (uptake studies) or porous
      membranes in bicameral chambers (transport/absorption studies). Caco-2, a human
      colon adenocarcinoma cell line, was selected as the test cell because it
      spontaneously differentiates into polarized enterocyte-like cells at confluency.
      Uptake of Fe (added as Fe-nitrilotriacetate complex) from a calcium-free solution
      by fully differentiated cells was 37 pmol/cm2. Addition of 10-fold molar excess
      of individual inositol phosphates (IP3, IP4, IP5 or IP6) decreased Fe solubility
      by 13 to 25% and reduced Fe uptake by 50 to 65%. The rate of transport of Fe from
      the apical solution into the basolateral chamber [1.4 +/- 0.1 pmol/(h.cm2)]
      decreased (34-96%) in proportion to the degree of phosphorylation of the inositol
      derivative in the apical compartment. Uptake and transepithelial transport of Zn
      were 246 +/- 5 pmol/cm2 and 23 +/- 1 pmol/(h.cm2), respectively. The solubility,
      uptake and rate of transport of Zn also decreased in proportion to the degree of
      phosphorylation of inositol. These results demonstrate the inhibitory influence
      of IP3-IP6 on the uptake and transport of Fe and Zn and support the usefulness of
      the Caco-2 human cell line as an appropriate model for evaluating the effects of
      specific dietary factors on trace metal bioavailability.

PMID- 8145082
TI  - Molybdenum but not copper counteracts cysteine-induced tibial dyschondroplasia in
      broiler chicks.
AB  - Studies were conducted to evaluate the ability of copper and molybdenum to
      prevent cysteine-induced tibial dyschondroplasia in broiler chicks. Experiment 1
      was a 3 x 3 factorial arrangement of treatments used to investigate the
      interaction between Cu (0, 150 or 300 mg/kg diet) and Mo (0, 10, or 100 mg/kg
      diet) on cysteine-induced tibial dyschondroplasia. Molybdenum at both
      supplemental levels, but not Cu, prevented cysteine-induced tibial
      dyschondroplasia. In Experiment 2 (a 3 x 3 factorial arrangement of treatments
      with 0, 5 or 10 g/kg diet of cysteine and 0, 10 or 100 mg/kg diet of Mo), Mo
      prevented cysteine-induced but not spontaneous tibial dyschondroplasia. Cysteine
      and Mo did not affect the mechanical properties of the tibiotarsus. In Experiment
      3, cysteine (0 or 10 g/kg diet) and Mo (0 or 100 mg/kg diet) were used to study
      the tissue concentrations of mineral and hepatic sulfite oxidase activity.
      Supplemental Mo increased Mo concentrations in the plasma and liver. Cysteine
      prevented these increases; however, cysteine, in the absence of supplemental Mo,
      did not affect concentrations of Mo in these tissues. Dietary cysteine and/or Mo
      did not affect tissue levels of Cu. We conclude that Mo prevents cysteine-induced
      tibial dyschondroplasia and that the induction of tibial dyschondroplasia by
      cysteine is not related to the Mo and Cu deficiency.

PMID- 8145083
TI  - Dietary fumonisin B1 induces disruption of sphingolipid metabolism in Sprague
      Dawley rats: a new mechanism of nephrotoxicity.
AB  - Fumonisins are potent inhibitors of sphingolipid biosynthesis produced by several
      Fusarium species. Consumption of corn or corn products infected with F.
      moniliforme, or high levels of fumonisins, is associated with several animal
      diseases. In a 4-wk feeding study, the concentration of fumonisin B1 that caused
      nephrotoxicity in Sprague-Dawley rats was much less than that required to cause
      hepatotoxicity. This retrospective study shows a close correlation between the
      extent and severity of ultrastructural lesions and the degree of disruption of
      sphingolipid metabolism. The kidney was more sensitive to fumonisin B1-induced
      disruption of sphingolipid metabolism than liver with significant elevation of
      free sphingosine, free sphinganine, and the free sphinganine:free sphingosine
      ratio in rats fed 15, 50 and 150 micrograms/g fumonisin B1. Accumulation of free
      sphinganine and elevation of the free sphinganine:free sphingosine ratio in urine
      closely reflected the changes that occurred in kidney. The accumulated
      sphinganine and elevation of the free sphinganine:free sphingosine ratio was
      associated with accumulation of cells in urine. Thus, urine rather than serum is
      the fluid of choice for detecting elevated free sphingoid bases generated as a
      consequence of fumonisin-induced kidney damage.

PMID- 8145084
TI  - Artifacts in computational optical-sectioning microscopy.
AB  - We tested the most complete optical model available for computational optical
      sectioning microscopy and obtained four main results. First, we observed good
      agreement between experimental and theoretical point-spread functions (PSF's)
      under a variety of imaging conditions. Second, using these PSF's, we found that a
      linear restoration method yielded reconstructed images of a well-defined phantom
      object (a 10-microns-diameter fluorescent bead) that closely resembled the
      theoretically determined, best-possible linear reconstruction of the object.
      Third, this best linear reconstruction suffered from a (to our knowledge)
      previously undescribed artifactual axial elongation whose principal cause was not
      increased axial blur but rather the conical shape of the null space intrinsic to
      nonconfocal three-dimensional (3D) microscopy. Fourth, when 10-microns phantom
      beads were embedded at different depths in a transparent medium, reconstructed
      bead images were progressively degraded with depth unless they were reconstructed
      with use of a PSF determined at the bead's depth. We conclude that (1) the
      optical model for optical sectioning is reasonably accurate; (2) if PSF shift
      variance cannot be avoided by adjustment of the optics, then reconstruction
      methods must be modified to account for this effect; and (3) alternative
      microscopical or nonlinear algorithmic approaches are required for overcoming
      artifacts imposed by the missing cone of frequencies that is intrinsic to
      nonconfocal 3D microscopy.

PMID- 8145085
TI  - Cyclic vomiting syndrome: a pediatric Rorschach test.

PMID- 8145086
TI  - Outpatient liver biopsy in children: has the time come?

PMID- 8145087
TI  - Intestinal neuronal dysplasia.

PMID- 8145088
TI  - When "buttoning up" is not sound advice.

PMID- 8145089
TI  - The cyclic vomiting syndrome: a report of 71 cases and literature review.
AB  - This study reviews 71 patients who presented between 1968 and 1988 with
      recurrent, self-limited episodes of nausea and vomiting separated by symptom-free
      intervals and were diagnosed with cyclic vomiting syndrome (CVS). The length and
      symptomatology of episodes tended to be stereotyped and characteristic for each
      patient over time. The disorder may persist from months to decades. There is a
      coincident relationship between CVS, migraine, and irritable bowel syndrome. The
      differential diagnosis includes many diseases which may mimic CVS. Management
      involves a responsive, collaborative doctor-patient relationship, sensitivity to
      stresses caused by the illness and to feelings and attitudes that may predispose
      to attacks, use of antiemetic agents to abort or shorten attacks, treatment of
      complications, and use of prophylactic agents in patients whose episodes are of
      sufficient frequency and severity to warrant their trial.

PMID- 8145090
TI  - Outpatient percutaneous liver biopsy in children.
AB  - We reviewed data from 184 percutaneous liver biopsies performed as an outpatient
      procedure in 104 patients (5 weeks to 22 years of age) over a 4-year period.
      Hepatic allograft rejection was the indication for 130 of the biopsy procedures,
      while 54 were performed for a variety of indications in patients who had not
      undergone transplant. Abnormalities of coagulation that necessitated correction
      were present in 19 patients at the time of biopsy. Patients tolerated the
      procedure well. There were no major complications. None of the patients required
      blood product transfusion or hospitalization as a result of the procedure. Two
      patients suffered respiratory depression as a complication of sedation, which was
      easily reversed with administration of intravenous naloxone. Two specimens were
      insufficient for interpretation. We conclude that percutaneous liver biopsy in
      the proper outpatient setting can reduce the need for hospitalization solely for
      the purpose of the procedure.

PMID- 8145091
TI  - Autoimmune hepatitis associated with anti-actin antibodies in children and
      adolescents.
AB  - The clinical, biochemical, morphological, and evolutive features of autoimmune
      hepatitis associated with serum smooth muscle antibodies of anti-actin
      specificity were retrospectively analyzed in 31 children and adolescents.
      Cirrhosis was present at diagnosis in all but six patients, including nine of the
      12 diagnosed within 6 months from the onset. In 15 children, one or more
      associated diseases of an immune-mediated mechanism were present, including
      chronic arthritis, sclerosing cholangitis, inflammatory bowel disease, and
      cutaneous vasculitis. All patients were treated with prednisone and azathioprine
      with normalization or improvement of liver function tests: 28 children are
      currently alive after a mean follow-up of 4 years, 10 months. Treatment was
      interrupted in four patients only. Two patients died of liver failure in spite of
      immunosuppressive therapy before the era of liver transplantation. In spite of
      prolonged therapy, five other patients ultimately required liver transplantation
      during adolescence or early adulthood. These results (a) further define a group
      of autoimmune hepatitis in children characterized by the presence of serum anti
      actin antibodies; (b) indicate that immunosuppressive therapy improves liver
      function, although in most cases it must be continued for a long period to
      maintain remission; and (c) suggest that progressive liver failure may occur in
      early adulthood and may require liver transplantation.

PMID- 8145092
TI  - Percutaneous endoscopic placement of the "button" gastrostomy tube as the initial
      procedure in infants and children.
AB  - Percutaneous endoscopic gastrostomy (PEG) tube placement is routinely performed
      in children with special nutritional needs. For convenience and cosmetic reasons,
      many parents prefer a skin-level, nonrefluxing, ("button") gastrostomy tube.
      After healing of the track, a button gastrostomy tube can replace a PEG but this
      requires a second procedure. This study assessed the technique and complication
      rate of placement of a button gastrostomy tube mounted for endoscopic placement
      as the initial procedure. Seventeen patients (10 males), ages 4 months to 12
      years were studied. All patients underwent successful placement of the button
      under conscious sedation using a standard endoscopic push technique. In the first
      10 patients, an 18 French device was used. Four patients developed migration of
      the device into the track between 9 and 55 days after placement and the button
      was removed. Migration was preceded or accompanied by a wound infection in 3 of
      the 4 patients. In the next 7 patients, a larger, 24 French button was used
      without any wound infections or migration of the device. In thirteen patients
      with successful placement, a follow-up period of 110-450 days has revealed no
      further complications. Placement of the button gastrostomy tube in infants and
      children can be accomplished using standard endoscopic techniques. However,
      further study of the optimal size of the device and optimal placement procedure
      to prevent wound infection and migration should be undertaken.

PMID- 8145093
TI  - Treatment of cyclic vomiting in childhood with erythromycin.
AB  - Cyclic vomiting syndrome is an unusual cause of episodic emesis in children. It
      manifests as intermittent episodes of severe vomiting, similar in time of onset
      and duration, with no symptoms during the intervening period. Dehydration
      necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers
      have proven unsuccessful. We report the use of erythromycin as a prokinetic agent
      in the treatment of cyclic vomiting in 20 children (9 boys, 11 girls). Many
      patients had mild associated abdominal pain with their vomiting. Thirteen
      patients had previously been given metoclopramide, but none responded. Two
      patients were mildly developmentally delayed. Twenty patients were given oral
      erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2-4 divided doses for
      7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of
      20 patients reported total resolution of symptoms when reevaluated at 2 and 6
      months. All males responded, 4 of 13 responders were female, and all seven with
      partial or no response to therapy were female. This uncontrolled trial suggests
      that erythromycin may be a useful prokinetic agent in the treatment of cyclic
      vomiting syndrome in childhood. As the study was uncontrolled, placebo effect
      cannot be excluded. Case-controlled, double-blinded prospective trials should be
      considered to evaluate the effectiveness of erythromycin in cyclic vomiting
      syndrome.

PMID- 8145094
TI  - Do umbilical vein catheterization and sepsis lead to portal vein thrombosis? A
      prospective, clinical, and sonographic evaluation.
AB  - Extrahepatic portal vein obstruction (EHPVO) affects 20-30% of all patients with
      portal hypertension in India. The etiopathogenesis of this disease is unknown. In
      retrospective studies, umbilical vein cannulation and sepsis have been alleged to
      cause portal thrombosis. This prospective study was undertaken to detect
      clinically and by serial sonography whether thrombosis and consequent obstruction
      of the splenoportal venous system develops after umbilical vein catheterization
      and sepsis. Forty-seven children who had undergone exchange transfusion for
      hyperbilirubinemia, belonging to two different age groups, were studied. Twenty
      two new-borns (Group A) were studied within 4 weeks of birth and later at 3-month
      intervals until the age of 12 months and subsequently at 24 months. Another group
      of 25 children (Group B), 1- to 5-year-olds who had earlier undergone exchange
      transfusion and 15 healthy newborns (Group C) were also screened. In Group A,
      seven (29%) neonates had septicemia, and in five, the splenic vein could not be
      initially visualized. The splenic vein was not seen in five of the 15 newborns in
      Group A who had no umbilical sepsis. Twenty-one of the 22 neonates in Group A
      were followed-up, and the splenic vein was well visualized and found patent on
      subsequent ultrasound in all of them. In Group B, four (16%) children had
      umbilical sepsis. None of these or the other Group B children showed any
      thrombosis or obstruction of the splenoportal system. The portal vein and its
      branches and the splenic vein were visualized in all healthy (Group C)
      neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145095
TI  - Asymptomatic uveitis in children with chronic inflammatory bowel diseases.
AB  - Uveitis may be an asymptomatic ocular process when it occurs in association with
      chronic inflammatory bowel disease (IBD). However, the frequency of uveitis in
      pediatric IBD is not known, as few patients have eye examinations on a routine
      basis. Experience with a child with Crohn's disease, who had asymptomatic uveitis
      identified by routine screening initiated because of associated arthritis,
      prompted us to undertake this evaluation. The purpose of this cross-sectional
      prospective study was to ascertain the point-prevalence of uveitis in pediatric
      IBD patients, including 97 with Crohn's disease and 50 with ulcerative colitis.
      Each child underwent an ophthalmologic assessment, including slit-lamp
      examination. In Crohn's disease, inflammatory cells and/or flare were observed in
      the anterior chamber of six (6.2%) patients. These changes were mild in all six
      patients and required no treatment. In the group with ulcerative colitis, there
      were no cases of asymptomatic uveitis. There was a higher frequency of
      asymptomatic transient uveitis in patients with Crohn's colitis (four of 22,
      18.2%) than in those of other anatomic subgroups (two of 75, 2.7%; p < 0.05).
      Frequency of uveitis was also higher in IBD patients having other extraintestinal
      manifestations (15.0%) than in those without (3.1%; p < 0.10). There was no
      relationship observed between the activity of bowel disease and presence of
      ocular inflammation.

PMID- 8145096
TI  - Longitudinal assessment of growth, mineral metabolism, and bone mass in pediatric
      Crohn's disease.
AB  - In children with inflammatory bowel disease, controversy continues about the use
      of long-term alternate day prednisone therapy (ADP) to suppress disease activity
      and to encourage appetite and growth. One possible side effect of both disease
      process and prednisone therapy is risk of development of osteoporosis. To
      evaluate this risk factor, growth, biochemical indices of mineral and vitamin D
      status, and bone mass were measured in nine adolescents with Crohn's disease (CD)
      who were treated with ADP (0.3 mg/kg > 3 months per year) compared with eight
      adolescents treated with minimal ADP exposure (< 3 months per year). Single
      photon densitometry was used to measure bone mineral mass at the 1/3 distal
      radius three times over 2 years. Mean age of the 17 CD boys was 13.9 +/- 2.1
      years at baseline. CD patients had lower bone BMC/BW mineral content/bone width
      (BMC/BW) compared with age- and height-matched normal boys at all times. The
      difference was less when compared to height-matched normal values as CD patients
      were shorter than healthy reference boys. Plasma 1,25-dihydroxyvitamin D,
      alkaline phosphatase, and parathyroid hormone significantly increased with
      treatment of disease but there were no differences between treatment groups. CD
      patients treated with ADP had similar heights and weights at baseline and
      demonstrated similar linear growth over 2 years (9.1 cm/2 years) to CD patients
      without ADP (10.3 cm/2 years). In both groups, BMC/BW increased significantly
      from year 1 to year 2, but absolute values for bone mass did not differ between
      the groups.

PMID- 8145099
TI  - Hydrogen sulfide in pediatric parenteral amino acid solutions.

PMID- 8145097
TI  - Comparative in vitro and in vivo studies of enteric-coated pancrelipase
      preparations for pancreatic insufficiency.
AB  - We evaluated three acid-resistant pancreatic enzyme preparations by in vitro
      assays, and by comparing degree of steatorrhea, creatorrhea, fecal wet weight,
      and stool energy losses in a randomized crossover study of patients with
      pancreatic insufficient cystic fibrosis. Aims of the study were to assess (a) the
      most practicable and reliable indicator of malabsorption; (b) the variation in
      enzyme batch potency; (c) the decline in enzyme batch potency with prolonged
      shelf life; and (d) the relative bioefficacy of the different preparations. In
      the in vivo study, absorption of energy, nitrogen, and fat did not differ when
      comparing the three preparations at roughly pharmaceutically equivalent doses,
      but when expressed per capsule of pancreatic supplement ingested, absorption
      reflected relative enzyme content, favoring the higher potency preparations.
      Although steatorrhea was reasonably controlled by these preparations, stool
      energy losses varied from 800 to 1,100 kJ per day, suggesting greater attention
      be paid to overall energy absorption rather than absorption of individual
      nutrients. In addition, fecal energy loss correlated more closely with fecal wet
      weight (r = 0.81; p < 0.05) than with steatorrhea (r = 0.40; ns), such that 1 g
      wet feces = 8.37 kJ (+/- 0.14). In vitro enzyme potency varied markedly between
      batches of the same brand, and also a decline of up to 20% in amylase, lipase,
      and trypsin activity was noted over an 8-month period for each batch. Both
      observations have clinical implications at times of represcription. Finally, the
      higher potency preparations were more effective per capsule and reduced capsule
      dosage is therefore attainable.

PMID- 8145098
TI  - Presence of multiple forms of peptidase inhibitors in rat milk.
AB  - Peptides such as somatostatin (SS14), epidermal growth factor (EGF), transforming
      growth factor-alpha (TGF alpha), and insulin-like growth factors (IGF-I and IGF
      II) are present in breast milk from various species, and their significance in
      the developing gastrointestinal tract has been suggested. Our recent studies have
      indicated that rat milk soluble fraction (RMSF) protects SS14 in the
      gastrointestinal lumen by inhibiting in vitro the luminal peptidolysis. In the
      present studies, we have shown that RMSF inhibited in vitro degradation by
      midjejunal luminal flushings of suckling rats of 125I-labeled somatostatin
      14[Tyr11], EGF, TGF alpha, IGF-I and IGF-II, as well as trypsin activity in vitro
      against benzoyl-L-arginyl-p-nitroanilide. The inhibitory factors present in the
      RMSF were further fractionated by gel filtration on Sephadex G100, ion-exchange
      chromatography on DEAE-Sephadex, and fast protein liquid chromatography (FPLC).
      Gel filtration of Sephadex G100 separated RMSF into three peaks of proteins: G1,
      G2, and G3; peptidase inhibitor activities were present exclusively in G1. Ion
      exchange chromatography on DEAE-Sephadex column resolved peptidase inhibitory
      activity (G1) into three different peaks, D1, D2, and D3, eluted at sodium
      chloride concentrations of 0.05 M, 0.1 M, and 0.2 M, respectively. Further
      purification of D2 by FPLC resulted in a fraction rich in peptidase inhibitory
      activity, which was essentially free of trypsin inhibitory activity. Results
      indicate the presence of at least three peptidase inhibitors in rat milk, which
      may play a role in the protection of milk-borne peptides in the gastrointestinal
      lumen.

PMID- 8145100
TI  - Polymorphonuclear leukocytes and human colostrum: effects of in vivo and in vitro
      exposure.
AB  - Polymorphonuclear leukocytes (PMN) from human colostrum were compared with blood
      and oral exudate PMN from the same donors for their locomotive, respiratory
      burst, phagocytic, and shape change (polarization) capabilities. Blood PMN were
      functionally superior to PMN from other sites. Colostrum PMN were similar to oral
      exudate PMN in all areas except locomotive responses. Exposure of blood PMN to
      aqueous human colostrum resulted in decreased stimulated adherence to plastic,
      decreased bactericidal activity against Staphylococcus aureus, reversible
      induction of cellular shape change, and reversible decreases in cellular
      deformability. The colostrum effects on PMN shape change and deformability were
      accompanied by significant increases in cytoskeleton-associated actin. PMN
      isolated from colostrum have suppressed functions, consistent with their being
      exudate cells. In addition, the colostrum environment effectively suppresses
      multiple functions in PMN from blood, these effects being mediated in part by
      rapid cytoskeletal assembly. PMN in colostrum do not appear to be beneficial to
      the breast-fed infant due to deficiencies in function.

PMID- 8145101
TI  - Focal nodular hyperplasia of the liver and hypercholesterolemia in a child with
      VACTERL syndrome.

PMID- 8145102
TI  - Neonatal hepatitis and congenital insensitivity to adrenocorticotropin (ACTH).

PMID- 8145103
TI  - Acute pancreatitis secondary to 5-aminosalicylic acid in a child with ulcerative
      colitis.

PMID- 8145104
TI  - Sulindac-induced regression of adenomatous colonic polyps in a child with a
      history of hepatoblastoma.

PMID- 8145105
TI  - Recurrent gastrointestinal bleeding associated with an abdominal lymphangioma:
      treatment by parenteral nutrition.

PMID- 8145106
TI  - Cow's milk-induced hematemesis in an infant.

PMID- 8145107
TI  - Salmonella's deceiving signals.

PMID- 8145108
TI  - How clinically relevant are disaccharide: monosaccharide ratios for assessing
      small intestine permeability?

PMID- 8145109
TI  - Liver involvement in infants with PiSZ phenotype of alpha 1-antitrypsin
      deficiency.

PMID- 8145110
TI  - Predictors of driving while intoxicated (DWI) among American Indians in the
      northwest.
AB  - This study compares DWI arrest records for American Indians to those of the
      general population in Washington State. Within the period January 1987 through
      December 1987, 1,067 American Indians were arrested for DWI. This sample was
      compared for age, gender, and occupational status to 28,130 total DWI arrestees
      during the same period. The data indicate that American Indians were the most
      over-represented population as they were two-and-one-half times as likely to be
      arrested for DWI, compared to overall DWI arrest population. The population of
      American Indians arrested for DWI was three times as likely to be unemployed as
      compared to the resident labor force of all American Indians. This research
      supports the conclusion that DWI arrests may be viewed as a symptom of alcohol
      misuse, abuse, or chemical dependency for American Indians, and that a DWI
      prevention approach should include education, prevention, intervention,
      treatment, aftercare, and law enforcement efforts that are sensitive to tribal
      diversity.

PMID- 8145111
TI  - School drug education programming: in search of a new direction.
AB  - School drug abuse prevention programs represent an enormous educational resource.
      Recent perceptions of an epidemic of drug abuse among the nation's youth have
      fueled the escalation in expenditures for drug prevention programming. An
      important question that needs to be addressed concerns whether broad ranging drug
      education efforts directed at all public and private school students are
      efficient and effective uses of available resources? After a brief survey of the
      evolution of drug education programming in the U.S., this article examines recent
      longitudinal research regarding the antecedents of drug abuse among young people.
      Based on this research, suggestions are made for a new approach to drug education
      programs which would direct intensive interventions at the minority of youth who
      are identifiable in early childhood as particularly susceptible to problems with
      drug abuse.

PMID- 8145112
TI  - Perceived harm, age, and drug use: perceptual and motivational dispositions
      affecting drug use.
AB  - Free associations reveal a close relationship between drug use and such
      psychological dispositions as dominant perceptions, attitudes, and systems of
      mental representations. The investigations reported here address the relationship
      of perceived harm or appeal of drugs, age, and reported drug use through analysis
      of the free associations of students from elementary to graduate school.
      Subsamples of drug users and non-users are also included. Comparisons across the
      range of years studied (10 to 29) showed how subjective meanings and the system
      of mental representation, including those characteristic of drug users and non
      users, evolve as a function of age. Based on the domains studied, the distance
      measured between user/non-user groups and between age groups showed systematic
      and predictable increases reflecting on construct validity. The perceptual and
      motivational dispositions identified were significantly correlated with drug use
      (behavioral validation). The results offer new insights into the role of such
      variables as perceived harm and subjective appeal.

PMID- 8145113
TI  - Stratification and smoking: a search for class-based smoking lifestyles.
AB  - This study looked for evidence of distinctive smoking lifestyles among social
      classes. Data on smoking attitudes and behaviors were collected via interviews of
      a representative sample of residents of a major western Canadian city. Four
      indicators of social class position (based on two approaches to conceptualizing
      social class) were employed. Regardless of the indicator of class used, few
      attitudinal or behavioral differences between social classes were found. The
      results suggest that the multi-faceted approach to smoking prevention in Canada
      has fostered a general climate of opinion which is antagonistic to smoking.
      Sociological factors which can lead to misperceptions of the extent of social
      class differences in smoking are discussed.

PMID- 8145114
TI  - Stages of drug use acquisition among college students: implications for the
      prevention of drug abuse.
AB  - The purpose of this study was to examine the stages of drug use acquisition among
      college students, and the relationship between stage status and motivation to
      avoid drugs and the frequency of drug use. Six hundred and sixty-nine students
      from a mid-size public university were selected to participate in the survey.
      College students were found to differ with regard to their stage of habit
      acquisition across five drugs. Stage status for a particular drug was associated
      with motivation to avoid that drug, with less motivation generally being related
      to greater stage advancement. Stage of acquisition for certain drugs was also
      found to be related to the frequency of use of other drugs, with alcohol and
      marijuana stage status being associated with the consumption of the greatest
      number of drugs. These results suggest that an acquisition stage heuristic holds
      promise in increasing our understanding of important developmental stages of drug
      use.

PMID- 8145116
TI  - The mark of a Christian nurse.

PMID- 8145117
TI  - Washing Irene's feet.

PMID- 8145115
TI  - An elementary school substance abuse prevention program: teacher and
      administrator perspectives.
AB  - Teachers and administrators from a large, diversified school district
      participated in a survey of perceived satisfaction, effectiveness, and degree of
      implementation of Project Pride, a substance abuse prevention program. As
      expected, degree of satisfaction with program content was consistently related to
      how beneficial and valuable teachers perceived the program to be for their
      students. The age appropriateness of materials and degree of difficulty in
      implementing activities were also significantly related to how much students
      benefitted from the program. Neither perceived support of administrators nor
      teacher participation in training was related to level of implementation or
      teacher satisfaction. The need to gather teacher and administrator perspectives
      about substance use prevention programs is discussed, as well as steps to be
      taken to maximize implementation of prevention curricula in elementary schools.

PMID- 8145118
TI  - A gift of life from a dying patient.

PMID- 8145119
TI  - Faith in action: an Appleton nurse reaches out to working poor. Interview by
      Robin Sheffield.

PMID- 8145120
TI  - Parish nursing: 20th-century fad?

PMID- 8145122
TI  - Lorraine Waite, RN--Zimbabwe's Mother Teresa. Interview by Barbara L. Flower.

PMID- 8145121
TI  - The illustrious class of 1947.

PMID- 8145123
TI  - Can I make a difference? The challenge of teaching community health workers in
      Somalia.

PMID- 8145124
TI  - What is Christian nursing?

PMID- 8145125
TI  - A journey of faith.

PMID- 8145127
TI  - Joy in the job.

PMID- 8145126
TI  - Why are you doing this for me?

PMID- 8145129
TI  - Simultaneous pharmacodynamic modeling of the non-steady-state effects of three
      oral doses of 1,3-glyceryl dinitrate upon blood pressure in healthy volunteers.
AB  - The organic nitrate 1,3-glyceryl dinitrate (1,3-GDN) is one of the primary
      dinitrate metabolites of the antianginal agent nitroglycerin (GTN).
      Investigational New Drug Approval was sought to administer oral solution doses of
      1,3-GDN to a small number (n = 3) of healthy volunteers; each subject receiving
      three doses at 1.2, 2.4, and 3.6 mg. With volunteers confined to a semirecumbent
      posture for the duration of each treatment (4-hr period postdose), diastolic
      blood pressure (DBP) was recorded and plasma samples collected for 1,3-GDN
      concentration analysis. Appreciable concentration-related decreases in DBP were
      observed, with maximal decreases from predose baseline values approximating 11 to
      25 mm Hg. For each subject parametric pharmacodynamic modeling was performed with
      simultaneous analysis utilizing the DBP vs. time data from all three doses; an
      inhibitory Emax pharmacodynamic model was adopted. The temporal relationship
      between plasma 1,3-GDN concentrations and DBP displayed rapid equilibration. For
      subjects 1, 2 and 3, respectively, Emax was predicted as 12.9, 23.4, and 29.7 mm
      Hg, representing 21.5, 31.6, and 39.5% decreases in DBP from predose baseline
      values; plasma concentrations at half Emax (C50) were 2.75, 2.43, and 5.93
      micrograms/L. Utilizing pharmacokinetic-pharmacodynamic modeling, 1,3-GDN plasma
      concentrations appear to relate to a systemic "effect measure" that is
      mechanistically representative of the therapeutic actions of organic nitrates as
      peripheral vasodilators. The establishment of a GDN plasma concentration-effect
      relationship together with the relatively high plasma levels of GDN achieved
      following GTN dosing supports the hypothesis that the GDNs contribute
      significantly to the hemodynamic effect observed with GTN.

PMID- 8145128
TI  - A mathematical model for dynamics of cardiovascular drug action: application to
      intravenous dihydropyridines in healthy volunteers.
AB  - A physiologically based mathematical model was built to describe the
      pharmacodynamic effects in response to the administration of intravenous (iv)
      dihydropyridine drugs in healthy volunteers. This model incorporates a limited
      number of hemodynamic variables, namely, mean arterial blood pressure (MAP),
      cardiac output (CO) or heart rate (HR), stroke volume (SV), and total peripheral
      resistance (TPR), into a closed-loop system supposed to represent essential
      features of the cardiovascular regulation. We also defined an additional
      auxiliary control variable (U) which is thought to represent primarily the role
      of the baroreceptor reflex. It was assumed that the variable U was related to MAP
      changes through both deviation- and rate-sensitive mechanisms. Other model
      parameters are the baseline levels for MAP, CO (or HR), and TPR, as well as time
      constants to account for further temporal aspects of the regulation. Finally, TPR
      was assumed to be linked to the plasma concentrations of dihydropyridine drugs
      via a conventional pharmacokinetic/pharmacodynamic (PK/PD) model, relying upon an
      effect compartment and a linear, hyperbolic, or sigmoidal relationship between
      the reduction in TPR and the drug concentrations at the effect site. The model
      characteristics were explored by studying the influence of various parameters,
      including baseline levels and deviation- and rate-sensitive control parameters,
      on the hemodynamic responses to a fictive constant rate i.v. infusion of a
      vasodilator drug. Attempts were also made to mimic literature data with
      nifedipine, following i.v. administration under both constant and exponentially
      decreasing infusion rates. The applicability of the model was demonstrated by
      fitting hemodynamic data following i.v. infusion of nicardipine to healthy
      volunteers, under experimental conditions similar to those described above for
      nifedipine. The effect model for the action of nicardipine on TPR, combined with
      the physiological model including a feedback control loop, allowed an adequate
      quantitative description of time profiles for both cardiac output and mean
      arterial pressure. The suggested model is a useful tool for integrated data
      analysis of hemodynamic responses to vasodilator drugs in healthy volunteers.
      Computer simulations suggest that a graded variation of a few model parameters-
      including baseline levels of TPR and MAP and the deviation-sensitive parameter of
      the arterial pressure control--would also be able to account for the pattern of
      hemodynamic response observed in hypertensive patients, which is qualitatively
      different to that seen in normotensive subjects. Extrapolation of drug response
      from the healthy volunteer to the hypertensive patient is allowed by our model.
      Its usefulness for an early evaluation of drug efficacy during drug development
      is under current investigation.

PMID- 8145130
TI  - Pharmacokinetics and pharmacodynamics of nitroglycerin and its dinitrate
      metabolites in conscious dogs: intravenous infusion studies.
AB  - Intravenous infusions of nitroglycerin (GTN), 1,2-glyceryl dinitrate (1,2-GDN),
      and 1,3-glyceryl dinitrate (1,3-GDN) were given to four conscious dogs at 10
      micrograms/min, 30 micrograms/min, 50 micrograms/min, and 70 micrograms/min of
      GTN and 20 micrograms/min and 100 micrograms/min of GDNs. The steady state plasma
      concentrations (Css) of GTN were reached after about 60 min whereas for 1,2-GDN
      and 1,3-GDN the Css were reached at about 150 min after the infusion began.
      Except for one dog, the Css of GTN were not proportional to infusion rate,
      however, all dogs together showed a good linear relationship between Css of GTN
      and infusion rates with an average correlation coefficient of 0.917 +/- 0.102.
      Large variability in GTN clearance after various infusion rates was observed in
      all dogs. The Css ratios of 1,2-GDN/GTN and 1,3-GDN/GTN yield overall averages of
      31.5 +/- 17.2 and 5.47 +/- 3.19, respectively. Average Css ratios of metabolites
      1,2-GDN/1,3-GDN were 5.78 +/- 1.23. This ratio is different from those obtained
      after iv bolus and oral dosing indicating that the biotransformation of GTN to
      1,2-GDN and 1,3-GDN differs for each dosing route. The clearances for 1,2-GDN and
      1,3-GDN were not changed over the dose range of 20 micrograms/min to 100
      micrograms/min. Terminal half-lives of 1,2-GDN and 1,3-GDN postinfusion were
      similar to those values obtained after a single bolus dose (45 min). It appears
      that all the GTN dose at steady state can be accounted for by the formation of
      measurable 1,2-GDN and 1,3-GDN. Large intra- and interdog variations in systolic
      blood pressure decrease (SPD) following infusions of GTN were observed, however,
      all dogs showed a clear systolic blood pressure decrease when the highest
      infusion rate (70 micrograms/min) was given. No significant systolic blood
      pressure drop was detected following 20 micrograms/min infusions of 1,2-GDN or
      1,3-GDN. It was clear that systolic blood pressure in all dogs decreased
      following 100 microgram/min infusions of 1,2-GDN or 1,3-GDN. When SPD values were
      plotted vs. log GTN concentrations following the infusion of 70 micrograms/min of
      GTN in all four dogs, a counterclockwise hysteresis was observed indicating the
      significant contribution of the active dinitrate metabolites to GTN
      pharmacodynamics.

PMID- 8145131
TI  - A physiological and system analysis hybrid pharmacokinetic model to characterize
      carbon tetrachloride blood concentrations following administration in different
      oral vehicles.
AB  - Oral absorption of chemicals can be influenced significantly by the
      administration vehicle or diluent. It has been observed that the oral absorption
      of carbon tetrachloride (CCl4) and other volatile organic chemicals is markedly
      affected by the dosing vehicle, with administration in oils producing erratic
      blood concentration-time profiles with multiple peaks. Analysis of this type of
      data by a compartmental modeling approach can be difficult, and requires numerous
      assumptions about the absorption processes. Alternatively, a system analysis
      method with few assumptions may provide a more accurate description of the
      observed data. In the current investigations, a nonlinear system analysis
      approach was applied to blood CCl4 concentration-time data obtained following iv
      and oral administration. The oral regimens consisted of 25 mg CCl4/kg body wt
      given as an aqueous emulsion, in water, as pure chemicals, and in corn oil. The
      system analysis procedure, based upon a disposition decomposition method,
      provided an absorption input rate function, F, for each regimen. A physiological
      pharmacokinetic model, based primarily on parameters available in the literature,
      and the F input functions, formed a hybrid model that adequately described the
      observed blood CCl4 concentration-time data. The same physiological
      pharmacokinetic model, employing conventional first-order absorption input
      schemes, did not predict the data as well. Overall, the system analysis approach
      allowed the oral absorption of CCl4 to be characterized accurately, regardless of
      the vehicle. Though system analysis is based on general mathematical properties
      of a system's behavior rather than on its causal mechanisms, this work
      demonstrates that it can be a useful adjunct to physiological pharmacokinetic
      models.

PMID- 8145133
TI  - Kinetics of combined drug action.
AB  - For the purpose of obtaining quantitative concentration-effect relationship for
      combined drugs, rationales of the Hill equation were inferred and five models,
      i.e., normal distribution (NRD), derivative of R (DRV), vacancy-dependent binding
      (VDB), equiresponse (EQR), and independence (IND), were proposed to estimate the
      intensity of the combined drug action. In conclusion, we could not come up to the
      unique concentration-effect relationship. Among the five models, the EQR, NRD,
      and VDB models gave almost identical response intensity. Discrimination of these
      three models is not of great importance. The DRV model gave a characteristic
      concave isobologram (overadditive), for a given ratio of Hill constants and
      independent of pharmacologic effect. In contrast, the IND model was able to cope
      with convex isobolograms (underadditive).

PMID- 8145132
TI  - Targeting anticancer drugs to the brain: II. Physiological pharmacokinetic model
      of oxantrazole following intraarterial administration to rat glioma-2 (RG-2)
      bearing rats.
AB  - The disposition of the anticancer drug oxantrazole (OX) was characterized in rats
      bearing the rat glioma-2 (RG-2) brain tumor. Following intraarterial
      administration of 3 mg/kg of OX, serial sacrifices were completed from 5 min to 5
      hr after administration. Blood and tissue samples collected at the time of
      sacrifice were processed and measured for OX concentrations by HPLC. The kidney
      had the greatest affinity for OX with the Cmax being 40.6 micrograms/ml at 15 min
      after administration. OX concentrations in brain tumor were higher than in normal
      right and left brain hemispheres, and consistent with enhanced drug blood-tumor
      barrier (BTB) permeability seen in experimental models for brain tumors. Observed
      heart, liver, lung, and spleen OX concentrations were similar, ranging from
      approximately 2 micrograms/ml to 20 micrograms/ml. A unique technique was used to
      develop a global physiological pharmacokinetic model for OX. A hybrid or forcing
      function method was used to estimate individual tissue compartment biochemical
      parameters (i.e., partition and mass transfer coefficients). A log likelihood
      optimization scheme was used to determine the best model structure and parameter
      sets for each tissue. Most tissues required a 3-subcompartment structure to
      adequately describe the observed data. The global model was then reconstructed
      with an arterial blood and rest of body compartments that provided predicted OX
      concentrations in agreement with the data. The model development strategy
      provides a systematic approach to physiological pharmacokinetic model
      development.

PMID- 8145134
TI  - Two constrained deconvolution methods using spline functions.
AB  - This paper describes two new methods to solve the following estimation problem.
      Given n1 noisy measurements (yi1, i = 1,..., n1) of the response of a system to a
      known input [A1(t) where t indicates time], and n2 noisy measurements (yi2, i =
      1,..., n2) of the response of a system to an unknown input [A2(t)], obtain an
      estimate of A2(t) and K(t) (the unit impulse response function of the system)
      under the model: [formula: see text] where Eij are independent identically
      distributed random variables. Both methods use spline functions to represent the
      unknown functions, and they automatically select the spline functions
      representing the unknown input and unit impulse response functions. The first
      method estimates separately the unit impulse response function and the input,
      recasting the problem in terms of inequality-constrained linear regression. The
      second method jointly estimates the unit impulse response function and the input
      function, recasting the problem in terms of inequality-constrained nonlinear
      regression. Simulated and real data analysis are reported.

PMID- 8145135
TI  - A link between adenosine, ATP-sensitive K+ channels, potassium and muscle
      vasodilatation in the rat in systemic hypoxia.
AB  - 1. In anaesthetized rats, systemic hypoxia evoked hyperventilation, tachycardia,
      a fall in arterial pressure, vasodilatation in skeletal muscle and increases in
      K+ concentration measured in arterial plasma ([K+]a), venous efflux from muscle
      ([K+]v) and in right atrial plasma ([K+]at). The ATP-sensitive potassium (K+ATP)
      channel inhibitor glibenclamide (10 or 20 mg kg-1 i.v.) reduced the muscle
      vasodilatation and increase in [K+]v, but had no significant effect on the other
      changes. 2. The adenosine receptor antagonist, 8-phenyltheophylline (8-PT, 10 mg
      kg-1 i.v.) had similar effects to glibenclamide. 3. Glibenclamide reduced the
      muscle vasodilatation evoked by the adenosine analogue, 2-chloroadenosine given
      i.v. (30 micrograms kg-1). 4. Infusion of adenosine (0.3 mg kg-1 min-1 for 5 min)
      into the hindlimb evoked muscle vasodilatation and an increase in [K+]v, both of
      which were abolished by 8-PT. 5. We propose that during systemic hypoxia, part of
      the muscle vasodilatation that can be attributed to adenosine is due to the
      action of K+, which is released from skeletal muscle fibres through glibenclamide
      sensitive K+ channels (possibly K+ATP channels) that are activated by adenosine.
      This may be a general mechanism for the vasodilator influence of adenosine.

PMID- 8145136
TI  - Evidence of incomplete neural control of motor unit properties in cat tibialis
      anterior after self-reinnervation.
AB  - 1. The mechanical, morphological and biochemical properties of single motor units
      from the anterior compartment of the tibialis anterior muscle in adult cats were
      studied six months after the nerve branches to that compartment were cut and
      resutured in close proximity to the muscle. 2. In these self-reinnervated
      muscles, the maximum tetanic tensions were lower in slow than fast units, a
      relationship similar to that observed among motor units from control adult
      muscles. The maximum tetanic tensions produced by the fast units were larger than
      those produced by the same motor unit types in control muscles. Direct counts of
      muscle fibres belonging to a motor unit showed that factors controlling the
      number of muscle fibres innervated by a motoneurone type persist during the
      reinnervation process in that fast motoneurones reinnervated more muscle fibres
      than slow motoneurones. Thus, the number of muscle fibres reinnervated by a
      motoneurone principally accounted for the difference in the maximum tension
      outputs among motor unit types, a relationship similar to that observed in
      control tibialis anterior muscles. 3. Monoclonal antibodies for specific myosin
      heavy chains were used to differentiate fibre types. By this criterion, motor
      units from control muscles were found to contain a homogeneous fibre type
      composition. In contrast, a heterogeneous, yet markedly biased, fibre type
      composition was observed in each unit analysed from self-reinnervated muscles. 4.
      Although not all of the muscle fibres of a motor unit developed the same type
      associated parameters after reinnervation, the relationships among myosin heavy
      chain profile, succinate dehydrogenase activity and the fibre size were similar
      in fibres of control and self-reinnervated muscles. 5. The processes which
      dictate both motor unit size and the matching between motoneurone and muscle
      fibre type during the reinnervation process must be interdependent and result
      from a hierarchy of decisions which reflects their relative importance. The
      mechanisms responsible for these two processes may be a combination of: (1)
      selective innervation which may or may not incorporate a pruning process if
      multiple synaptic connections are initially formed and/or (2) conversion of
      enough fibres of a motor unit to form a predominant type.

PMID- 8145137
TI  - Relationship between intracellular pH and metabolite concentrations during
      metabolic inhibition in isolated ferret heart.
AB  - 1. Intracellular pH (pHi) and phosphorus metabolites were measured in isolated
      ferret hearts with 31P nuclear magnetic resonance (NMR). 2. The application of
      cyanide (to mimic hypoxia) produced a fall of the concentration of
      phosphocreatine ([PCr]) and a rise of those of inorganic phosphate ([Pi]) and
      sugar phosphates. These were accompanied by an intracellular acidosis. 3. If
      glycolysis was partly inhibited by prior exposure to a glucose-free solution then
      the application of cyanide also produced a fall of [ATP]. The acidosis was
      similar to that observed in the presence of glucose. 4. If glycolysis was
      completely inhibited by iodoacetate then the acidosis produced by subsequent
      addition of cyanide developed more quickly. 5. The results are reproduced by a
      model which incorporates lactic acid production as well as the effects of protons
      released and absorbed by the changes in metabolite concentrations. The results
      suggest that the acidosis produced by cyanide (without inhibition of glycolysis)
      is largely due to lactic acid production. When glycolysis is partly inhibited
      (glucose-free solution) the acidosis produced by cyanide is partly due to protons
      released by ATP breakdown. Finally, when glycolysis is entirely inhibited the
      acidosis is completely due to ATP breakdown. There is no need to postulate a
      contribution on this time scale from inhibition of pH regulating mechanisms.

PMID- 8145138
TI  - Birefringence changes associated with isometric contraction and rapid shortening
      steps in frog skeletal muscle fibres.
AB  - 1. Muscle birefringence, the difference between the refractive indices of light
      polarized parallel and perpendicular to the muscle fibre axis, was measured at 3
      degrees C in intact single fibres isolated from frog muscle. Resting
      birefringence was 2.20 +/- 0.02 x 10(-3) (mean +/- S.E.M., n = 44) at sarcomere
      length 2.4-2.7 microns and 2.35 +/- 0.03 x 10(-3) (n = 19) at 3.5-3.8 microns. 2.
      Birefringence decreased during isometric twitch or tetanic contractions. The peak
      change in a twitch at sarcomere length 2.6 microns, determined by two independent
      methods, was 0.150 +/- 0.017 x 10(-3) (mean +/- S.E.M., n = 6). The corresponding
      value after 0.4 s of tetanic stimulation was 0.167 +/- 0.012 x 10(-3) (n = 6). 3.
      The birefringence change had a shorter latency than tension and reached its half
      maximum value earlier than tension. The difference in time to half-maximum in
      tetani was 11.5 +/- 1.3 ms (mean +/- S.E.M., n = 6) at 3 degrees C. After
      stimulation birefringence recovered to its pre-stimulus baseline more slowly than
      tension. 4. The birefringence decrease after 0.4 s of tetanic stimulation was
      linearly related to the expected degree of overlap between actin and myosin
      filaments in the sarcomere length range 2.6-3.6 microns. The amplitude of the
      birefringence decrease at full filament overlap (sarcomere length 2.2 microns)
      was estimated to be 0.235 +/- 0.015 x 10(-3). 5. Birefringence changes associated
      with shortening steps of 0.9% fibre length at sarcomere length 2.6 microns
      exhibited four phases corresponding to those of the tension transient. There was
      no consistent birefringence change during the length step itself. During the
      rapid tension recovery birefringence increased by 0.014 +/- 0.001 x 10(-3) (n =
      3), measured from the end of the length step to 2 ms later. Birefringence
      continued to increase as tension recovery slowed, reaching a peak about 10 ms
      after the step, then recovered with a rate similar to that of the final tension
      recovery. 6. These birefringence changes are likely to be caused by axial
      rotation of the head domain of the myosin cross-bridge. During isometric
      contraction heads bind to actin with their long axes more perpendicular to the
      fibre axis than in resting muscle, although there is likely to be a wide range of
      head orientations during contraction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145139
TI  - Asynchrony of mossy fibre inputs and excitatory postsynaptic currents in rat
      hippocampus.
AB  - 1. Excitatory postsynaptic currents (EPSCs) were studied by whole-cell voltage
      clamp recording (WCR) from pyramidal cells in the CA3 field of rat hippocampal
      slices. Input from mossy fibres was evoked by stimuli applied to stratum
      granulosum ('dentate gyrus stimulation'). This often resulted in complex, multi
      component EPSCs with rise times as long as 5.0 ms (mean = 2.5 ms). In contrast,
      individual EPSC components typically had rise times between 0.3 and 1.0 ms. 2. To
      isolate monosynaptic, mossy fibre-driven EPSC components, slices were exposed to
      'suppressing' media that reduced response amplitudes by 64-88%. In five out of
      six cases, long EPSC rising phases (> 3 ms) retained the same shape during
      suppression. This implied that EPSCs were driven by asynchronously active mossy
      fibre inputs. 3. From latencies of antidromically driven granule cell population
      spikes (GCPSs) a mean conduction velocity of 0.67 m/s was inferred. Conduction
      distance had practically no correlation with GCPS duration, implying that
      velocity dispersion was small and did not desynchronize mossy fibre impulses.
      EPSC components exhibited 'surplus' latency; they occurred 0.9-4.8 ms after
      latencies expected on the basis of direct conduction distances. 4. Mossy fibre
      volleys (MFVs) were evoked by dentate gyrus stimulation and studied with
      neurotransmission disabled. MFV negative phases lasted from 2.5 to 4.5 ms and had
      multiple components. By comparison, negative phases of Schaffer collateral fibre
      volleys (SCFVs) were always simple in shape and lasted 1.5 ms or less. MFV
      components had surplus latencies similar to those of EPSC components. Late MFV
      components did not require high stimulus intensities. 5. Widespread activation of
      granule cells occurred when stimuli were applied to single loci in the stratum
      granulosum. This implies that such stimuli elicit antidromic impulses in hilar
      collaterals of mossy fibres, which could result in activation of orthodromic
      impulses in mossy fibre trunks that had not been stimulated directly. After anti
      , then orthodromic conduction, impulses would arrive in the CA3 subfield with
      'surplus' latency. 6. When cuts were made in the hilus to prevent anti
      /orthodromic conduction, MFV durations were reduced, but only to a small extent.
      This implies that surplus latency and asynchrony arise in part by anti
      /orthodromic conduction, and partly by a mechanism that is intrinsic to mossy
      fibres or their 'giant' boutons. 7. Because of desynchronization of mossy fibre
      inputs, there probably are significant differences between kinetic properties of
      averaged, compound mossy fibre EPSCs and those of unitary mossy fibre EPSCs (i.e.
      currents driven by input from single presynaptic axons).(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8145140
TI  - Activation of internodal potassium conductance in rat myelinated axons.
AB  - 1. Voltage changes associated with currents crossing the internodal axolemma were
      monitored using a microelectrode inserted into the myelin sheath (peri-internodal
      region) of rat phrenic nerve fibres. This microelectrode was also used to change
      the potential and the ionic environment in the peri-internodal region. 2.
      Following stimulation of the proximal nerve trunk, the peri-internodal electrode
      recorded a positive-going action potential whose amplitude increased (up to 75
      mV) with increasing depth of microelectrode penetration into the myelin. The
      resting potential recorded by the peri-internodal electrode remained within 4 mV
      of bath ground. 3. Confocal imaging of fibres injected peri-internodally with the
      fluorescent dye Lucifer Yellow revealed a staining pattern consistent with spread
      of dye throughout the myelin sheath of the injected internode. 4. After
      ionophoresis of K+ (but not Na+) into the peri-internodal region, the action
      potential was followed by a prolonged negative potential (PNP) lasting hundreds
      of milliseconds to several seconds. The duration of the PNP increased as the
      frequency of stimulation decreased. PNPs could also be evoked by sub-threshold
      depolarization of the internodal axolemma with peri-internodally applied current
      pulses. In the absence of action potentials or applied depolarization PNPs
      sometimes appeared spontaneously. 5. Peri-internodal application of Rb+ also
      produced evoked and spontaneous PNPs. These PNPs had longer durations (up to 20
      s) than those recorded from K(+)-loaded internodes. 6. Spontaneous action
      potentials sometimes appeared during the onset of the PNP, suggesting that PNPs
      are associated with depolarization of the underlying axon. 7. Passage of current
      pulses during the PNP demonstrated that the PNP is associated with an increased
      conductance of the pathway linking the peri-internodal recording site to the
      bath. At least part of this conductance increase occurs across the internodal
      axolemma, since peri-internodally recorded action potentials evoked during the
      PNP had larger amplitudes than those evoked before or after the PNP. 8. PNPs were
      suppressed by tetraethylammonium (TEA, 10-20 mM) and by 4-aminopyridine (1 mM).
      9. These results suggest that the PNPs recorded in K(+)- or Rb(+)-loaded myelin
      sheaths are produced by a regenerative K+ or Rb+ current that enters the
      internodal axolemma via K+ channels opened by action potentials or subthreshold
      depolarizations. 10. When normal extracellular [K+] was preserved (by using Na+
      rather than K+ salts in the peri-internodal electrode), action potentials
      recorded within the myelin sheath were instead followed by a brief, positive
      after-potential that was inhibited by TEA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145141
TI  - Occurrence of intracellular pH transients during spontaneous contractions in rat
      uterine smooth muscle.
AB  - 1. Intracellular pH (pHi) and contraction have been measured simultaneously in
      isolated longitudinal rat myometrium. Tissue was loaded with the pH-sensitive
      fluorophore carboxy-SNARF and superfused with oxygenated, buffered salt solution
      at 37 degrees C and pH 7.4. 2. Small (0.04 pH unit) transient intracellular
      acidifications followed each spontaneous uterine contraction. The pHi transients
      lagged contraction by 15 s. Removal of external Ca2+ abolished both spontaneous
      contractions and the pHi changes. 3. Increasing uterine contraction by
      depolarization (40 mM K+) or agonist (50 microM carbachol) produced a larger
      acidification (0.18 pH unit). 4. The acidification with contraction does not
      appear to be due to increased glycolysis as no increase in lactate efflux
      occurred with high-K+ stimulation. 5. Uterine contraction is known to be
      sensitive to changes in pHi. Comparable pHi changes to the pHi transients seen
      during spontaneous contraction were induced by application and withdrawal of weak
      acids and bases. The resulting pHi changes (0.02-0.08 pH unit) produced effects
      on contraction frequency and amplitude, alkalinization augmenting and
      acidification depressing contractile activity, suggesting that the pHi transients
      with contraction are functionally important.

PMID- 8145142
TI  - Parasympathetic non-adrenergic, non-cholinergic mechanisms in reflex secretion of
      parotid acinar granules in conscious rats.
AB  - 1. Female adult rats were subjected to sympathetic denervation of the parotid
      glands by bilateral removal of the superior cervical ganglion 10-12 days before
      acute experiments. The sympathectomy was in some of the experimental groups
      combined with either bilateral adrenal medullectomy, treatment with the sensory
      neurotoxin capsaicin or parasympathetic denervation of the gland by cutting the
      auriculotemporal nerve. 2. Food but not water was withheld for 29-32 h before
      acute experiments. All animals were given an intraperitoneal injection of
      phentolamine (2 mg kg-1) and propranolol (1 mg kg-1) and, when appropriate, also
      atropine (1 mg kg-1). Then the experimental animals were fed their ordinary food
      of hard chow for 60-90 min. Thereafter, these animals and their non-fed controls
      were killed, and the parotid glands were removed and used for either morphometric
      assessment or measurement of amylase activity. 3. In the atropinized rats
      subjected to sympathectomy alone, eating reduced the numerical density of acinar
      secretory granules by 50% and the total activity of amylase by 55%; the
      corresponding figures were, when sympathectomy was combined with adrenal
      medullectomy, 51 and 63%. Also, in atropinized animals subjected to sympathectomy
      and capsaicin pretreatment, eating reduced the numerical density of acinar
      granules and the total amylase activity, in this case by 45 and 35%,
      respectively. 4. In the atropinized rats subjected to sympathectomy and
      parasympathectomy, eating caused no change in the numerical density of acinar
      granules but reduced the total amylase activity by 35%. 5. In the non-atropinized
      rats subjected to sympathectomy alone, eating reduced the numerical density of
      acinar granules by 22%, while there was no change in the total amylase activity.
      6. In conclusion, eating evoked a reflex activation of the sympathectomized
      parotid gland that engaged non-adrenergic non-cholinergic receptors of the acinar
      cells. The present results give weight to a physiological role for non-adrenergic
      non-cholinergic parasympathetic mechanisms in salivary secretion under reflex
      conditions.

PMID- 8145143
TI  - The physiological regulation of synaptic inhibition by GABAB autoreceptors in rat
      hippocampus.
AB  - 1. Intracellular recording techniques were used to study the effects of
      repetitive stimulation on monosynaptically activated inhibitory postsynaptic
      currents (IPSCs) in rat hippocampal slices. This was achieved by stimulation in
      stratum radiatum close to a recorded CA1 pyramidal neurone after pharmacological
      blockade of excitatory synaptic responses, using a combination of the N-methyl-D
      aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptor antagonists D-2-amino-5-phosphonopentanoate (AP5; 0.04-0.1 mM) and 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.02-0.04 mM), respectively. 2. Fixed
      intensity stimulation at frequencies of less than 0.1 Hz evoked biphasic IPSCs of
      constant amplitude and waveform. In contrast, when two shocks (paired pulse) or
      longer trains of ten or more stimuli (i.e. tetani) were delivered at frequencies
      of between 0.2 and 20 Hz there was marked depression of both phases of every IPSC
      (by 60-100%) relative to the first or 'priming' IPSC evoked. 3. The gamma
      aminobutyric acid (GABA)B receptor antagonists phaclofen (0.4-2 mM), 2-hydroxy
      saclofen (0.02-0.4 mM) and 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP
      35348; 0.01-1 mM) reduced or abolished, in a concentration-dependent and
      reversible manner, both the late phase of the IPSC (IPSCB) and paired-pulse
      depression of the early phase of the IPSC (IPSCA). Expressed in terms of IC50
      values, all three antagonists were 5-10 times more potent at blocking IPSCB than
      paired-pulse depression. 4. Paired-pulse depression, at 5 and 10 Hz, has been
      shown to be mediated by GABA acting on presynaptic GABAB receptors (i.e. GABAB
      autoreceptors). We now show that GABAB receptor antagonists reverse paired-pulse
      depression over the entire range of frequencies (0.1-50 Hz) that it occurs. 5.
      GABAB receptor antagonists reversed substantially the depression of IPSCs during
      tetani delivered at 5 or 10 Hz. However at 20 Hz, GABAB receptor antagonists
      appeared to be less effective. At 100 Hz they appeared to be ineffective at
      reversing the depression of IPSCA; since the antagonists block IPSCB the net
      effect was to reduce the level of outward current. 6. At frequencies of 20 Hz or
      more, there was also the appearance of a slow inward current which increased in
      size in proportion to the frequency and number of shocks in the tetanus. This
      current (termed here IPSCI) was more pronounced at hyperpolarized membrane
      potentials and was blocked by picrotoxin (0.1 mM) or bicuculline (0.05 mM). 7.
      'Priming' is considered to represent a more physiological pattern of activity
      than a tetanus.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145144
TI  - Analysis of the propagation of disinhibition-induced after-discharges along the
      guinea-pig hippocampal slice in vitro.
AB  - 1. A model has been proposed of picrotoxin-induced hippocampal in vitro after
      discharges; it depends critically upon alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the recurrent
      excitatory connections between pyramidal neurones, and upon the ability of
      pyramidal neurones to generate bursts at about 10 Hz when their dendrites are
      sufficiently depolarized. 2. We study here the question of whether this model can
      account for spatial--as well as temporal--aspects of after-discharges in guinea
      pig hippocampal slices. For example, can the model explain the propagation along
      a transverse slice of the initial burst and the secondary bursts at about the
      same velocity, approximately 0.10-0.20 m s-1? Under what conditions might the
      secondary bursts exhibit a different spatial pattern to the initial burst, as we
      now show can occur in longitudinal slices? To examine these questions, we
      increased the number of cells in our model from 100 to 8000 (in a 20 x 400
      array), arranging the excitatory synaptic connections in a spatially restricted
      fashion, with an average extent of 1.0 mm (as suggested experimentally). 3. Our
      model suggests that both AMPA and NMDA receptors contribute to the propagation
      pattern and velocity of the initial and the secondary bursts in an after
      discharge. 4. When unitary AMPA and NMDA conductances are in the range where the
      primary burst lasts for 100-200 ms, and there are three or four secondary bursts,
      then both primary and secondary bursts propagate near to the experimentally
      observed velocity for transverse slices. In the model, however, secondary bursts
      propagate at somewhat slower velocities than the initial burst. 5. The mechanisms
      of propagation are different for the initial and for the secondary bursts:
      propagation of the primary burst depends upon the initiation of electrogenesis in
      'resting' dendrites by AMPA and NMDA inputs that are rapidly increasing in time.
      Propagation of secondary bursts depends upon the timing of calcium spikes in
      depolarized dendrites with slowly varying NMDA inputs; the timing of calcium
      spikes can be influenced by a 'wave' of AMPA input, but calcium spikes--we
      predict--should occur even without the AMPA input, once the after-discharge has
      been initiated. The blockade of firing in an intermediate region of the
      disinhibited slice is predicted to have different effects on the primary burst
      and on secondary bursts distal to the region of blockade.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8145145
TI  - Na+ channels in cardiac and neuronal cells derived from a mouse embryonal
      carcinoma cell line.
AB  - 1. Cells from a pluripotent murine embryonal carcinoma cell line (P19) were
      differentiated in vitro into cells with neurone- and cardiac-like phenotypes.
      Cells treated with 0.5 microM retinoic acid developed into neurone-like cells
      possessing extensive neurites. Dimethyl sulphoxide treatment (0.5%) produced
      large, spontaneously contracting cell aggregates with many properties of cardiac
      cells. 2. The neurone- and cardiac-like cells contained voltage-sensitive Na+
      channels with properties similar to those of native neuronal and cardiac cells.
      3. We used whole-cell patch clamp techniques to measure inward currents from the
      neurone- and cardiac-like cells. Undifferentiated (untreated) cells had only
      small inward currents (peak of -0.15 nA in 150 mM external Na+). The peak inward
      current in the neurone-like and cardiac-like cells was -1.2 nA (in 154 mM
      external Na+) and -2.8 nA (in only 46 mM Na+), respectively. These large currents
      were absent when the external solution contained no Na+. 4. Tetrodotoxin (TTX)
      blocked the Na+ currents in the neurone- and cardiac-like cells in a dose
      dependent manner. The Kd for TTX block of the Na+ current in the neurone-like
      cells was 6.7 nM. The Na+ current in the cardiac-like cells was much more
      resistant to TTX; the half-blocking concentration was two orders of magnitude
      higher, 710 nM. 5. The kinetic properties of the Na+ channel currents in the
      neurone- and cardiac-like cells were similar but developed over somewhat
      different voltage ranges. The voltage sensitivity of activation was similar in
      both cell types but the activation mid-point voltage was different: -12 mV in the
      neuronal cells and -34 mV for cardiac cells. Inactivation of the neuronal Na+
      channels had a mid-point near -47 mV and was more sensitive to the membrane
      voltage than inactivation of the cardiac channels. The mid-point of inactivation
      for the cardiac Na+ channels was -80 mV.

PMID- 8145146
TI  - Opposite effects of phosphatase inhibitors on L-type calcium and delayed
      rectifier currents in frog cardiac myocytes.
AB  - 1. Application of the phosphatase inhibitors okadaic acid (OA) and microcystin
      (MC) to frog cardiomyocytes caused large increases in L-type calcium current
      (ICa) in the absence of beta-adrenergic agonists. The increase occurred without
      effects on the peak current-voltage relation or voltage-dependent inactivation.
      OA and MC caused a decrease in amplitude of delayed rectifier current (IK), which
      is opposite to the increase produced by cAMP-dependent phosphorylation. The
      decrease occurred without effects on voltage-dependent activation or reversal
      potential. 2. Analysis of the dose-response relations for OA and MC on
      ventricular cell ICa were best fitted with a single-site relationship with a K1/2
      of 1.58 microM and 0.81 microM, respectively. These data suggest the predominant
      form of phosphatase active on ICa in this cell type is produced by protein
      phosphatase 1. Inhibition of phosphatase 2B (calcineurin) was without appreciable
      effect. 3. Reducing intracellular ATP levels was without effect on basal ICa
      suggesting that calcium channels may not need to be phosphorylated to open. ATP
      depletion was able to block completely the ICa increase induced by OA or MC. This
      demonstrates that the effects of OA and MC on ICa are mediated by a
      phosphorylation reaction. In contrast, ATP depletion totally abolished IK,
      suggesting either a requirement for ATP or phosphorylation for basal function of
      the delayed rectifier channel. 4. Internal perfusion of a peptide inhibitor
      (PKI(5-22)) of protein kinase A (PK-A) was without effect on basal current levels
      of ICa or IK, suggesting that this kinase is not phosphorylating these channels
      under basal conditions. Furthermore, although PKI is capable of completely
      blocking the response of ICa to isoprenaline or forskolin, PKI does not affect
      the increase in ICa induced by MC or OA. Inhibition of adenylate cyclase with
      acetylcholine or inhibition of PK-A with adenosine cyclic 3',5'-(Rp)
      phosphothioate (Rp-cAMPS) also had no effect on the response to OA or MC. 5.
      Application of beta-adrenergic agonist, forskolin or cAMP all produced additional
      increases in the presence of saturating doses of MC or OA. This supports the
      hypothesis that PK-A is not mediating the OA response and that phosphatase
      inhibition does not result in complete phosphorylation of PK-A sites. 6. To
      attempt to identify the protein kinase activity responsible for OA effects on ICa
      and IK, several types of protein kinase inhibitors were internally
      perfused.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145147
TI  - Dual modulation of K+ currents and cytosolic Ca2+ by the peptide TRH and its
      derivatives in guinea-pig septal neurones.
AB  - 1. We describe a dual effect of the peptide TRH (thyrotrophin-releasing hormone)
      and its derivatives at concentrations between 0.1 and 1 microM on the K+ currents
      and cytosolic Ca2+ concentration in enzymatically dispersed septal neurones. 2.
      In response to membrane depolarization, septal neurones recorded under whole-cell
      patch clamp can generate two major K+ currents: (i) a fast and transient K+
      current (I(t)), that after a maximum at 2-5 ms inactivates completely at all
      membrane potentials in less than 50 ms; and (ii) a slowly activating current
      (I(s)), which reaches a maximum in 15-20 ms and does not exhibit appreciable
      inactivation during short-lasting voltage pulses. 3. In about 70% of the neurones
      tested (n = 48) TRH induced a reversible, and often transient, increase of I(t),
      I(s) or both K+ conductaNces. In approximately 10% of the cells the peptide had
      an opposite effect and caused a more protracted and partially reversible
      attenuation of the amplitude of I(t) and I(s). 4. The dual action of TRH on the
      K+ currents was mimicked by its derivatives but the effects varied depending on
      their structural relationship with the precursor neuropeptide. The physiological
      metabolite cyclo-His-Pro and the synthetic analogue methyl-TRH, in which the
      carboxyl terminus of the molecule is conserved, increased the K+ currents,
      whereas depression of the K+ conductances was predominantly observed in the
      presence of TRH-OH, in which the amino end of TRH is maintained intact. 5. In
      fura-2-loaded unclamped cells, TRH induced either release of Ca2+ from internal
      stores, Ca2+ entry, or both. With TRH-OH we never observed mobilization of
      internal Ca2+ but this peptide evoked a large Ca2+ influx. 6. The results
      demonstrate that the physiological metabolites of brain TRH (cyclo-His-Pro and
      TRH-OH) have biological activity. TRH and its derivatives exert two types of
      regulatory actions on the voltage-gated K+ channels and cytosolic Ca2+
      concentration in central neurones, which can be explained assuming that TRH and
      TRH-derived products interact with different subtypes of brain receptors
      recognizing preferentially either the amino or the carboxyl termini of the TRH
      molecule.

PMID- 8145148
TI  - Microheterogeneity of subsarcolemmal sodium gradients. Electron probe
      microanalysis in guinea-pig ventricular myocytes.
AB  - 1. The effect of stimulation on possible subsarcolemmal sodium accumulation was
      studied in ventricular myocytes (2 mM [Ca2+]o, 36 degrees C). By trains of
      eighteen paired voltage-clamp pulses (180 ms to 0 mV, 20 ms to -45 mV, 180 ms to
      +50 mV, 620 ms to -45 mV) unloaded contractions were potentiated to an optimum.
      2. Potentiation reversibly enlarged and prolonged the diastolic tail currents due
      to Na(+)-Ca2+ exchange. Eighteen pulse pairs were estimated to provide a sodium
      influx that could increment the total intracellular sodium concentration (sigma
      Na(i)) by no more than 0.5 mM. 3. Potentiation reversibly increased the current
      at +50 mV and made it more noisy. Cell-attached recordings with a second
      electrode attributed this noise to the activation of K+ (Na) channels. In inside
      out patches, a comparable channel activity was obtained with 40 mM sodium. Hence,
      the cell-attached recordings suggest that potentiation can increase intracellular
      sodium concentration to 40 mM. 4. Electron probe microanalysis (EPMA) measured
      sigma Na in a volume within 20 nm of the inner side of the sarcolemma.
      Potentiation reversibly increased sigma Na20nm to 40 +/- 7 mM. When stimulation
      was terminated, sigma Na20nm fell within 8 s to 37 +/- 8 mM and within 3 min to
      19 +/- 6 mM. In unstimulated cells sigma Na20nm was 17 +/- 5 mM. 5. In
      potentiated cells, shock-frozen at early systole, sigma Na fell with a space
      constant of 28 nm from the sarcolemma to the centre; at 1 microns distance sigma
      Na was 12 +/- 3 mM. The steep gradient suggests that sodium does not freely
      diffuse and sigma Na20nm is controlled by transmembrane fluxes rather than by
      cell dialysis. 6. sigma Na20nm data were distributed with peaks at 5, 30 and 60
      mM. Quantitative elemental digital imaging demonstrated patches with 60-80 mM
      sigma Na20nm alternating with others of 0-15 mM sigma Na20nm. This 'sodium
      microheterogeneity' suggests that Ca2+ efflux at low sigma Na20nm and K+(Na)
      channel activation at high sigma Na20nm can operate simultaneously.

PMID- 8145149
TI  - Calcium buffering properties of calbindin D28k and parvalbumin in rat sensory
      neurones.
AB  - 1. We have examined the ability of the Ca(2+)-binding proteins (CABP) calbindin
      D28k and paravalbumin to modulate increases in the intracellular free Ca2+
      concentration ([Ca2+]i), produced by brief depolarizations, in rat dorsal root
      ganglion (DRG) neurones. 2. In order to obtain good voltage control, we replated
      DRG neurones prior to performing these experiments. Immunocytochemical staining
      of these cells revealed that approximately 10% stained for CABPs. 3. Using
      fluorescently labelled parvalbumin, we demonstrated that in the whole-cell
      voltage clamp mode the protein freely entered the cell soma with a mean half-life
      t0.5 of 6 min 22 s +/- 54 s. 4. Analysis of the effects of calbindin D28k (370
      microM) and parvalbumin (1 mM) on Ca2+ currents in the whole-cell voltage clamp
      mode, revealed that neither protein changed the rate of inactivation of the Ca2+
      current or its rate of run-down. 5. Introducing either calbindin D28k (370
      microM) or parvalbumin (1 mM) into the cell soma did not significantly alter the
      basal [Ca2+]i when compared to control cells. 6. Compared to control cells, both
      CABPs significantly reduced the peak [Ca2+]i obtained for a Ca2+ influx of an
      equivalent charge density, whereas lysozyme (1 mM), a protein with low affinity
      for Ca2+, failed to do so. 7. Calbindin D28k caused an 8-fold decrease in the
      rate of rise in [Ca2+]i and altered the kinetics of decay of [Ca2+]i to a single
      slow component. Parvalbumin also slowed the rate of rise in [Ca2+]i. Parvalbumin
      selectively increased a fast component in the decay of the Ca2+ signal. 8. These
      data demonstrate that both calbindin D28k and paravalbumin effectively buffer
      Ca2+ in a cellular environment and may therefore regulate Ca(2+)-dependent
      aspects of neuronal function.

PMID- 8145150
TI  - Modulation by histamine of an inwardly rectifying potassium channel in human
      endothelial cells.
AB  - 1. Whole-cell and single-channel currents were recorded together with
      intracellular Ca2+ in voltage clamped, single endothelial cells isolated from
      human umbilical vein. 2. The major current component under resting conditions in
      the whole-cell configuration was a strongly inwardly rectifying potassium
      current. 3. This current is due to activation of a K+ channel with an inward
      conductance of 29 +/- 3 pS (n = 7) with symmetrical 140 mM K+ on both sides of
      the membrane. This channel could be measured both in the cell-attached and in the
      inside-out configuration. At potentials below -110 mV both whole-cell and
      averaged single-channel currents showed a fast inactivation. 4. During
      stimulation of endothelial cells with histamine, whole-cell K+ currents initially
      increased but then substantially declined, despite the sustained increase in
      intracellular Ca2+ concentration ([Ca2+]i). 5. The blockade of the inwardly
      rectifying K+ channel by histamine could not be observed in cell-attached patches
      if histamine was added to the bath. 6. It is concluded that endothelial cells
      possess K+ channels that are directly inhibited by agonists, such as histamine.
      Blocking these channels may depolarize the cell membrane and thereby reduce the
      driving force for Ca2+ influx.

PMID- 8145151
TI  - Role of sodium-calcium exchange in activation of contraction in rat ventricle.
AB  - 1. The functional role of reverse Na(+)-Ca2+ exchange in the activation of
      contraction of rat ventricular myocytes has been studied. Mechanical activity of
      single cells, measured as unloaded cell shortening, was recorded simultaneously
      with membrane current and voltage using a single microelectrode voltage clamp and
      a video edge detection device. 2. The voltage dependence of contraction was
      studied by applying trains of depolarizations. At test potentials between +20 and
      +80 mV (under conditions where large outward currents were activated) a plateau
      on the shortening vs. voltage (S-V) relationship was observed. Significant cell
      shortening also occurred at test potentials between -70 and -40 mV; and these
      contractions were accompanied by large inward Na+ currents. We have investigated
      the ionic mechanisms for three components of the S-V relation in rat ventricle:
      (i) shortening which occurs between -70 and -40 mV and is thought to be dependent
      on the sodium current; (ii) phasic contractions in the voltage range -40 to +40
      mV where the L-type Ca2+ current is present; (iii) the plateau of the S-V
      relation at strongly depolarized voltages where reverse Na(+)-Ca2+ exchange may
      occur. 3. Experiments in which two independent microelectrode impalements were
      made in a single myocyte showed that during activation of contraction at test
      potentials between -70 and -40 mV, and during very large depolarizations (+20 to
      +80 mV), there were significant deviations of the measured membrane potential
      from the applied voltages. Activation of cell shortening in these voltage ranges
      could be eliminated by electronic series resistance compensation, which
      significantly reduced these voltage errors. Consistent with these findings, when
      tetrodotoxin (TTX) and 4-aminopyridine (4-AP) were used to block inward Na+ and
      transient outward K+ currents, respectively, no significant voltage errors were
      present and a bell-shaped shortening-voltage (S-V) relationship was obtained. 4.
      When Na+ and K+ currents were blocked, depolarizations from holding potentials of
      either -80 or -50 mV demonstrated that the threshold for activation of
      contraction was about -30 mV, and that the voltage dependence of peak shortening
      was very similar to that of the L-type Ca2+ current (ICa,L). These contractions
      were suppressed completely by either Cd2+ or ryanodine, showing that activation
      of cell shortening was due to Ca2+ influx through L-type channels which induced
      release of Ca2+ from the sarcoplasmic reticulum (SR). No T-type calcium currents
      were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145152
TI  - The role of Na(+)-Ca2+ exchange in paired pulse potentiation of ferret
      ventricular muscle.
AB  - 1. Stimulation of cardiac muscle with pairs of stimuli ('paired pulse
      stimulation') results in a large inotropic effect and experiments have been
      carried out on ferret ventricular muscle to investigate the underlying mechanism.
      2. Aequorin was used to measure sarcoplasmic Ca2+ in papillary muscles. During
      paired pulse stimulation the first aequorin light transient (i.e. Ca2+ transient)
      and contraction of the pair increased in amplitude, whereas the second aequorin
      light transient and contraction were small. When the interval between the pair
      was decreased, the second aequorin light transient and contraction of the pair
      were smaller, but the increase in the first aequorin light transient and
      contraction was greater. 3. The relationship between contraction and the aequorin
      light transient was the same during paired pulse stimulation and on raising the
      bathing Ca2+ concentration. It is concluded that there was no change in the
      myofilament sensitivity to Ca2+ during paired pulse stimulation. 4. The increase
      in the aequorin light transient and contraction during paired pulse stimulation
      was prevented by ryanodine, an inhibitor of the sarcoplasmic reticulum (SR). 5.
      During paired pulse stimulation of ventricular myocytes there was little change
      in the first action potential of the pair, but the second action potential was
      shorter than control when the interval between the pair was short. During paired
      pulse stimulation of ventricular myocytes under voltage clamp control there was
      little change in the first Ca2+ current (iCa) of the pair, but the second iCa was
      smaller than control when the interval between the pair was short. Because paired
      pulse potentiation was greatest when the interval between the pair was short, it
      is concluded that paired pulse potentiation was not the result of a prolongation
      of the action potential or increase in iCa. 6. During paired pulse stimulation of
      ventricular myocytes under voltage clamp control the increase in contraction was
      greater, the more positive the membrane potential during the second pulse of the
      pair. This voltage dependence is consistent with a role for the Na(+)-Ca2+
      exchanger in paired pulse potentiation. 7. During paired pulse stimulation of
      ventricular myocytes under voltage clamp control, changes in putative Na(+)-Ca2+
      exchange current were observed consistent with a decrease of Ca2+ efflux (or
      increase of Ca2+ influx) via the exchanger during the second pulse of the pair.
      8. A computer model of excitation-contraction coupling (Harrison, McCall &
      Boyett, 1992) has been used to simulate paired pulse stimulation and the results
      described above.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145153
TI  - Turnover rate of the cardiac Na(+)-Ca2+ exchanger in guinea-pig ventricular
      myocytes.
AB  - 1. Single guinea-pig ventricular myocytes were voltage clamped using the whole
      cell configuration of the patch-clamp technique and membrane current generated by
      the Na(+)-Ca2+ exchange mechanism recorded. 2. Rapid increases in cytosolic free
      calcium ([Ca2+]i) evoked by flash photolysis of either nitr-5 or DM-nitrophen
      resulted in current relaxations, arising from a redistribution of exchanger
      carrier conformations induced by the changes in [Ca2+]i. 3. Relaxation time
      constants were temperature dependent with a temperature coefficient over a 10
      degrees C range (Q10) of approximately 3 and also voltage dependent, decreasing
      on hyperpolarization for membrane potentials in the range +40 to -80 mV. 4. The
      experimental results are consistent with consecutive exchange models having
      electrogenic Na+ translocation steps, together with a site density and turnover
      rate similar to that for the Na(+)-K+ pump.

PMID- 8145154
TI  - Differential effect of injections of kainic acid into the prepositus and the
      vestibular nuclei of the cat.
AB  - 1. In order adequately to control eye movements, oculomotoneurones have to be
      supplied with both an eye-velocity signal and an eye-position signal. However,
      all the command signals of the oculomotor system are velocity signals. Nowadays,
      there is general agreement about the existence of a brainstem network that would
      convert velocity command-signals into an eye-position signal. This circuit,
      because of its function, is called the oculomotor neural integrator. The most
      obvious symptom of its eventual failure is a gaze-holding deficit: in this case,
      saccades are followed by a centripetal post-saccadic drift. Although the
      oculomotor neural integrator is central in oculomotor theory, its precise
      location is still a matter for debate. 2. Previously, microinjections of kainic
      acid (KA) into the region of the nucleus prepositus hypoglossi (NPH) and of the
      medial vestibular nucleus (MVN) were found to induce a horizontal gaze-holding
      failure both in the cat and in the monkey. However, the relatively large volumes
      (1-3 microliters) and concentrations (2-4 micrograms microliters-1) used in these
      injections made it difficult to know if the observed deficit was due to a
      disturbance of the NPH or of the nearby MVN. These considerations led us to
      inject very small amounts of kainic acid (50 nl, 0.1 microgram microliter-1)
      either into the rostral part of the MVN or into different sites along the NPH of
      the cat. 3. The search coil technique was used to record (1) spontaneous eye
      movements (2) the vestibulo-ocular reflex (VOR) induced by a constant-velocity
      rotation (50 deg s-1 for 40 s) and the optokinetic nystagmus (OKN) elicited by
      rotating an optokinetic drum at 30 deg s-1 for 40 s. 4. In each injection
      experiment, the location of the abducens nucleus of the alert cat was mapped out
      by recording the antidromic field potentials evoked by the stimulation of the
      abducens nerve. Two micropipettes were then glued together in such a way that
      when the tip of the recording micropipette was in the centre of the abducens
      nucleus the tip of the injection micropipette was in a target area. The twin
      pipettes were then lowered in the brainstem until the recording micropipette
      reached the centre of the abducens nucleus. Kainic acid was then injected into
      the brainstem of the alert cat through the injection micropipette by an air
      pressure system. 5. Carried out according to such a protocol, KA injections into
      the NPH or the rostral part of the MVN consistently led to specific eye-movement
      changes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145155
TI  - Ca2+ and Sr2+ entry induced Ca2+ release from the intracellular Ca2+ store in
      smooth muscle cells of rat portal vein.
AB  - 1. Changes in cytosolic free Ca2+ concentration ([Ca2+]i) induced by membrane
      depolarizations were investigated using indo-1 microspectrofluorimetry in single
      patch-clamped smooth muscle cells of rat portal vein at room temperature (20-21
      degrees C) and in the presence of 2 mM Ca2+. 2. During a 1 s depolarization from 
      50 to -30 mV [Ca2+]i rose, but, although the Ca2+ current was terminated by
      repolarization to -50 mV, [Ca2+]i continued to increase in a regenerative manner.
      The delay between the end of the voltage step and the peak of the [Ca2+]i rise
      was reduced by increasing the depolarization. 3. When a second identical
      depolarization was rapidly applied (8-13s) after the first one, it induced an
      identical Ca2+ current but a smaller increase in [Ca2+]i which started to decay
      upon repolarization. 4. A low concentration of caffeine (0.05 mM), applied to
      cells showing a small depolarization-induced [Ca2+]i transient which reached a
      peak at the end of the voltage step, produced an increase in amplitude and in
      duration of the [Ca2+]i rise without changing the amplitude of the depolarization
      induced Ca2+ current. 5. The depolarization-induced [Ca2+]i rise was shortened
      and reduced in amplitude after noradrenaline- (NA 10 microM) or caffeine- (5 mM)
      induced release of Ca2+ store and when the patch pipette solution contained
      ryanodine (100 microM). Under these conditions, the depolarization-induced
      [Ca2+]i transient was maximal at the end of the voltage step and declined
      immediately when the membrane was repolarized at -50 mV. 6. Experiments were done
      by replacing extracellular Ca2+ by Sr2+. Depolarization-induced Sr2+ entry
      through voltage-dependent Ca2+ channels could evoke an increase in indo-1
      fluorescence which occurred after the termination of the voltage step. This
      delayed component of fluorescence increase displayed properties similar to those
      of the regenerative [Ca2+]i rise recorded in the Ca(2+)-containing solution. 7.
      The inefficiency of the second of two successive depolarizations to produce the
      delayed component of [Ca2+]i rise was not due to the emptiness of the
      intracellular Ca2+ store since, under these conditions, caffeine was still able
      to induce a Ca2+ release. 8. It is concluded that depolarization-evoked Ca2+ or
      Sr2+ entry through voltage-dependent Ca2+ channels induced the release of Ca2+
      from an intracellular store, which could occur in a regenerative manner,
      independent of the termination of the triggering current.

PMID- 8145156
TI  - Respiration-synchronous fluctuations in stroke volume, heart rate and arterial
      pressure in humans.
AB  - 1. Simultaneous recordings of beat-to-beat left cardiac stroke volume (SV, pulsed
      ultrasound Doppler), mean arterial pressure (MAP) and heart rate (HR) were
      obtained in ten healthy young adults during spontaneous respiration at supine
      rest, before and after cholinergic blockade by atropine (0.035 mg kg-1). 2.
      Respiration-synchronous fluctuations in SV, HR, cardiac output (CO) and MAP were
      quantified by spectral analysis of the recordings of each of these variables. 3.
      Before atropine administration, respiration-synchronous fluctuations in HR and SV
      were prominent. The changes in HR and SV were inversely related and variation in
      SV was the main source of respiratory variability in CO. Respiration-synchronous
      fluctuations in MAP were mainly caused by variations in CO. 4. After cholinergic
      blockade, respiratory HR variations were eliminated, whereas the respiratory
      fluctuations in SV persisted. The fluctuations in CO and MAP increased. In this
      situation, mechanically induced variations in SV were not counteracted by inverse
      HR fluctuations and the influence on CO thus increased. 5. The main source of
      respiratory fluctuations in MAP in supine humans is thus variation in SV, while
      inverse, vagally mediated HR variations tend to reduce the fluctuations in CO and
      MAP.

PMID- 8145157
TI  - Effect of positive and negative step changes in intrathoracic pressure on left
      ventricular function in conscious man.
AB  - 1. Breathing affects left ventricular stroke volume (LVSV) in normal subjects.
      The observed relationship may result from interaction between the effects of
      changing lung volume and intrathoracic pressure (IP). 2. To investigate the
      effect of IP on LVSV with minimal changes in lung volume, beat-by-beat LVSV
      (pulsed Doppler ultrasound) and systemic blood pressure (Finapres) were measured
      during obstructed inspiratory and expiratory efforts causing step changes in IP
      of +/- 15 cmH2O for 10 s, in seven subjects. Changes in mouth pressure (MP)
      during airway occlusion were used to indicate changes in IP. Group-averaged data
      for each second were compared to that in the second before the change in MP using
      Dunnet's multiple range test. 3. Step reductions in MP resulted in immediate and
      significant falls in LVSV (P < 0.05) and systolic blood pressure (P < 0.01) and
      increased heart rate, although this was not significant. These responses were
      transient, lasting only 3 s despite 10 s of reduced MP. 4. Step increases in MP
      caused biphasic cardiovascular responses. LVSV increased immediately, then fell
      significantly below control after 8 s (P < 0.01). Heart rate increased
      significantly between 5 and 9 s after the onset of the increase in MP (P < 0.05),
      suggesting activation of the baroreflexes by the accompanying progressive fall in
      systolic blood pressure. 5. The asymmetry in time course and magnitude between
      the responses to positive and negative pressure may reflect asymmetrical effects
      of MP on systemic venous return, right ventricular output, pulmonary venous
      return and left ventricular (LV) after-load, with the baroreceptors limiting
      changes in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145158
TI  - Na(+)-K+ pump stimulation elicits recovery of contractility in K(+)-paralysed rat
      muscle.
AB  - 1. This study explores the role of active electrogenic Na(+)-K+ transport in
      restoring contractility in isolated rat soleus muscles exposed to high
      extracellular potassium concentration ([K+]o). This was done using agents
      (catecholamines and insulin) known to stimulate the Na(+)-K+ pump via different
      mechanisms. 2. When exposed to Krebs-Ringer bicarbonate buffer containing 10 mM
      K+, the isometric twitch and tetanic force of intact muscles decreased by 40-69%.
      The major part of this decline could be prevented by the addition of salbutamol
      (10(-5) M). In the presence of 10 mM K+, force could be restored almost
      completely within 5-10 min by the addition of salbutamol or adrenaline and partly
      by insulin. 3. In muscles exposed to 12.5 mM K+, force declined by 96%.
      Salbutamol (10(-5) M), adrenaline (10(-6) M) and insulin (100 mU ml-1) produced
      57-71, 61-71 and 38-47% recovery of force within 10-20 min, respectively. The
      effects of these supramaximal concentrations of salbutamol and insulin on force
      recovery were additive. Salbutamol and adrenaline produced significant recovery
      of contractility at concentrations down to 10(-8) M (P < 0.005). 4. In soleus,
      the same agents stimulated 86Rb+ uptake and decreased intracellular Na+. These
      actions reflect stimulation of active Na(+)-K+ transport and both showed a highly
      significant correlation to the recovery of twitch as well as tetanic force (r =
      0.80-0.88; P < 0.001). 5. The force recovery induced by salbutamol, adrenaline
      and insulin was suppressed by pre-exposure to ouabain (10(-5) M for 10 min or 10(
      3) M for 1 min) as well as by tetrodotoxin (10(-6) M). 6. The observations
      support the conclusion that the inhibitory effect of high [K+]o on contractility
      in skeletal muscle can be counterbalanced by stimulation of active electrogenic
      Na(+)-K+ transport, the ensuing increase in the clearance of extracellular K+ and
      in the transmembrane electrochemical gradient for Na+.

PMID- 8145159
TI  - Neural and biomechanical specializations of human thumb muscles revealed by
      matching weights and grasping objects.
AB  - 1. Human manual dexterity has been linked by some to biomechanical adaptations of
      the hand and by others to neural adaptations. To investigate neural adaptations,
      the present study using the performance of four muscles acting on the index and
      thumb, quantified weight matching and electromyography. 2. The accuracy (i.e.
      reproducibility) of weight matching was used to investigate whether thumb muscles
      (i.e. flexor pollicis longus (FPL) and adductor pollicis (AP)) perform
      differently from index muscles (i.e. flexor digitorum profundus (FDP) and first
      dorsal interosseous (FDI)), and whether intrinsic hand muscles (AP and FDI)
      perform differently from extrinsic ones (FPL and FDP). 3. Subjects lifted
      reference weights on the right which represented predetermined percentages of a
      force generated in a maximum voluntary contraction (MVC) ranging from 2.5% to 35%
      MVC (and to 50% MVC in two muscles) and matched them with a variable weight
      lifted in the same way on the left. 4. Analysis of the coefficients of variation
      (c.v., expressed as a percentage) and the standard deviations calculated for
      repeated estimates of perceived heaviness, revealed significant differences in
      the accuracy of weight matching between different muscles and between reference
      weights. Based on the c.v., subjects lifted more accurately with FPL and AP (the
      two thumb muscles) than with the two index muscles. The two intrinsic hand
      muscles (FDI and AP) were equally accurate, and significantly more accurate than
      FDP which was the least accurate muscle. The high accuracy for FPL remained when
      accuracy was expressed in terms of the torque produced by the muscles when
      lifting the reference weights, and also when the torques were converted to
      absolute intramuscular forces. 5. Accuracy (based on c.v.) decreased
      significantly with light weights and increased with heavy weights for all muscles
      except FPL, which was equally accurate over a very wide range of weights (< 2.5%
      to 50% MVC). When data from all muscles were pooled, the c.v. increased from 12.9
      to 19.1 as the weights lifted decreased from 35% to 2.5% MVC. 6. To examine the
      functional implications of the weight-matching study, electromyographic activity
      (EMG) was recorded with fine-wire electrodes from the same four muscles while
      subjects lifted cylinders of different widths (17-50 mm) and weights (15-1000 g).
      For recordings in which integrated EMG was linearly related to force up to
      maximal levels, the amplitudes of the EMGs at 'lift off' and at the mid-point of
      the 'hold' phase of the task were expressed relative to the maximal EMG during a
      MVC.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145160
TI  - Mild hypoxaemia does not alter red blood cell production in fetal sheep.
AB  - 1. Fetal sheep at 120 days gestation were fitted with upper and lower body
      arterial and venous catheters in addition to a flow sensor and occluder placed
      around the aorta below the renal arteries. 2. After 7 days of recovery, the
      occluder was partially inflated to reduce aortic blood flow to 70% of control.
      Blood flow reduction was maintained at this level for the remainder of the
      experiment. 3. Blood samples were taken after 60 min of blood flow reduction and
      again after 3 or more days of blood flow reduction. 4. There was no change in
      upper body arterial or venous blood pressure. Lower body arterial blood pressure
      decreased, as expected. Arterial PO2 decreased while packed cell volume and
      haemoglobin concentration increased. There was no change in plasma erythropoietin
      concentrations or plasma renin activity. 5. While both red cell mass and
      haemoglobin mass increased during the period of the study, the rate of increase
      was no different from the rate of blood volume increase.

PMID- 8145161
TI  - Control of frequency during swimming in Xenopus embryos: a study on interneuronal
      recruitment in a spinal rhythm generator.
AB  - 1. In Xenopus embryos, the frequency of natural and fictive swimming usually
      drops slowly as swimming continues but can increase following stimulation of the
      skin or dimming of the illumination. We have investigated whether such increases
      are associated with an increase in the number of neurones active at higher
      frequencies. 2. Recordings from ventral presumed motoneurones show that these
      were reliably active at all swimming frequencies. 3. Recordings from more dorsal
      presumed interneurones showed that in the majority of these firing probability
      decreased as a function of swimming frequency. Dye-filled microelectrodes were
      used to show that some of these neurones had the anatomy of known classes of
      excitatory and inhibitory premotor interneurones. 4. If skin stimulation is given
      at appropriate phases of the swimming cycle, it can lead to a transient increase
      in frequency. Recordings from silent premotor interneurones during such
      stimulation show that they can be recruited to fire during the post-stimulus
      frequency increases. 5. It was possible that spike failure in the interneurones
      could have been due to damage by the recording microelectrodes. We therefore
      measured the amplitudes and probability of occurrence of rhythmic 'on-cycle'
      IPSPs which occur in sensory interneurones and 'on-cycle' IPSPs which sometimes
      occur in motoneurones during fictive swimming. Both decreased in amplitude and
      could fail as frequency dropped, providing further evidence that the number of
      inhibitory interneurones firing on each cycle of swimming is a function of
      frequency. 6. We conclude that premotor rhythm-generating interneurones are not
      active on all cycles of swimming and that their probability of firing action
      potentials increases with swimming frequency. This suggests that swimming
      frequency is determined in part by the number of premotor interneurones which are
      active.

PMID- 8145162
TI  - The spatial distribution of calcium signals in squid presynaptic terminals.
AB  - 1. The fluorescent Ca2+ indicator dye, fura-2, was used to examine the spatial
      distribution of intracellular Ca2+ signals in giant presynaptic terminals of
      squid. Brief trains of presynaptic action potentials were evoked to open Ca2+
      channels within the giant presynaptic terminals and elevate presynaptic Ca2+
      concentration. 2. Electrical stimulation produced pronounced rises in presynaptic
      Ca2+ concentration. These rises were much larger in the terminal region than in
      the adjacent axonal region of the presynaptic neuron, suggesting that Ca2+
      channels are most abundant in the terminal. 3. Stimulation also produced
      gradients in Ca2+ concentration across the width of the presynaptic terminal.
      During stimulation, Ca2+ concentration was highest in the compartment of the
      presynaptic terminal closest to the postsynaptic neuron. This suggests that the
      Ca2+ channels are localized to this region of the presynaptic terminal. 4.
      Following the end of action potential trains, the rises in Ca2+ concentration
      became uniform across the width of the terminal. The redistribution of Ca2+
      presumably is due to diffusion of Ca2+ throughout the presynaptic cytoplasm.
      Stimulus-evoked rises in Ca2+ declined slowly over several tens of seconds. 5.
      Histological examination of a giant presynaptic terminal used for imaging
      experiments revealed that the spatial compartments where stimulus-induced rises
      in Ca2+ concentration were highest were also enriched in active zones, the
      presynaptic sites of transmitter secretion. The co-localization of Ca2+
      transients and active zones strongly suggests that neurons cluster Ca2+ channels
      selectively at active zones and that they do so to enhance the magnitude of Ca2+
      signals in the vicinity of the active zone. 6. Longitudinal gradients in Ca2+
      concentration also occur within presynaptic terminals and can be quantitatively
      accounted for by gradients in surface/volume ratio and density of active zones
      along the length of the presynaptic terminal.

PMID- 8145163
TI  - Maximum velocity of shortening in relation to myosin isoform composition in
      single fibres from human skeletal muscles.
AB  - 1. Maximum velocity of shortening (Vmax) and compositions of myosin heavy chain
      (MHC) and myosin light chain (MLC) isoforms were determined in single fibres from
      the soleus or the lateral region of the quadriceps (vastus lateralis) muscles in
      man. Muscle samples were obtained by percutaneous biopsy, and membranes were
      permeabilized by glycerol treatment (chemical skinning) or by freeze-drying. 2.
      Types I, IIA and IIB MHCs were resolved from single fibre segments by 6% sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and five different
      fibre types were identified: fibres containing type I MHC, types I and IIA MHCs,
      type IIA MHC, types IIA and IIB MHCs, and type IIB MHC. Only a few fibres co
      expressed types I and IIA MHCs but 28% of all quadriceps fibres expressed both
      IIA and IIB MHCs in variable proportions. Fibres co-expressing types I and IIB
      MHCs were not found. 3. Alkali (MLC1 and MLC3) and dithio nitrobenzoic acid
      (DTNB) (MLC2) myosin light chains were observed in all type II fibres in variable
      proportions. MLC (MLC1s and MLC2s) isoforms from type I fibres had lower
      migration rates than the corresponding isoforms from type II fibres (MLC1f and
      MLC2f). More than half of type I fibres in both soleus (65%) and quadriceps (68%)
      muscles also expressed 'fast' MLC3 and 36% of the type II fibres from quadriceps
      muscle expressed the slow isoform of MLC2. 4. Differences were observed in some
      mechanical characteristics of freeze-dried versus chemically skinned fibres.
      Maximum tension (P0) and specific tension were lower in freeze-dried types I and
      IIA fibres than in chemically skinned, while no differences were observed in the
      IIA/B fibres. The numbers of types I/IIA and IIB fibres were too low to allow
      statistical comparisons. In chemically skinned fibres, mean specific tension
      (0.20 +/- 0.01 N/mm2) did not vary with fibre type. In freeze-dried fibres, on
      the other hand, specific tensions varied according to MHC type: higher (P < 0.01)
      specific tensions were observed in types IIB (0.19 +/- 0.01 N/mm2) and type IIA/B
      fibres (0.18 +/- 0.04 N/mm2) than in type I fibres (0.12 +/- 0.02 N/mm2). The
      specific tension of type IIA fibres (0.12 +/- 0.05 N/mm2) did not differ
      significantly from the other fibre types. Cross-sectional areas and mean Vmax did
      not differ between freeze-dried and chemically skinned fibres, either when all
      fibres were pooled or within respective fibre types. Vmax data from all fibres of
      a given type, irrespective of membrane permeabilization technique, have therefore
      been pooled.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145164
TI  - Energetics of fast- and slow-twitch muscles of the mouse.
AB  - 1. The energetic cost of work performance by mouse fast- and slow-twitch muscle
      was assessed by measuring the rates of thermal and mechanical energy liberation
      of the muscles at 21 degrees C. Thermal energy (heat) liberation was measured
      using a fast-responding thermopile. 2. Bundles of muscles fibres from the slow
      twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles were used.
      Work output was controlled by performing isovelocity shortenings during the
      plateau of an isometric tetanus. A range of shortening velocities, spanning the
      possible range, was used for each muscle. 3. During tetanic contractions, the
      rate of heat production from EDL muscle was 134.2 +/- 11.4 mW/g. The rate of heat
      production by soleus muscle was only one-fifth as great (26.8 +/- 2.7 mW/g). 4.
      The maximum shortening velocity (Vmax) of EDL muscles was 2.5-fold greater than
      that for soleus muscles and it's force-velocity relationship was less curved.
      Peak power output from EDL muscles was 3-fold greater than that from soleus
      muscle. 5. During shortening, the rate of heat output from soleus muscles
      increased considerably above the isometric heat rate. In contrast to soleus
      muscle, the rate of heat production by EDL muscle increased by only a small
      fraction of the isometric heat rate. The magnitude of the increases in rate was
      proportional to shortening velocity. 6. The total rate of energy liberation (heat
      rate + power) by EDL muscle, shortening at 0.95 Vmax was 1.62 +/- 0.37 times
      greater than the isometric heat rate. In contrast, the rate of energy liberation
      from soleus muscle shortening at 0.95 Vmax was 5.21 +/- 0.58 times greater than
      its isometric heat rate. The peak mechanical efficiency (power/total energy rate)
      of the both muscles was approximately 30%.

PMID- 8145165
TI  - Exocytosis elicited by action potentials and voltage-clamp calcium currents in
      individual mouse pancreatic B-cells.
AB  - 1. Measurements of membrane capacitance, as an indicator of exocytosis, and
      intracellular Ca2+ concentration ([Ca2+]i) were used to determine the Ca2+
      dependence of secretion in single pancreatic B-cells. 2. Exocytosis was dependent
      on a rise in [Ca2+]i and could be evoked by activation of voltage-dependent Ca2+
      currents. The threshold for depolarization-induced release was 0.5 microM
      [Ca2+]i. Once the [Ca2+]i threshold was exceeded, exocytosis was rapidly (< 50
      ms) initiated. When individual pulses were applied, exocytosis stopped
      immediately upon repolarization and the Ca2+ channels closed, although [Ca2+]i
      remained elevated for several seconds. 3. During repetitive stimulation (1 Hz),
      when [Ca2+]i attained micromolar levels, exocytosis also took place during the
      interpulse intervals albeit at a slower rate than during the depolarizations. 4.
      Exocytosis could be initiated by simulated action potentials. Whereas a single
      action potential only produced a small capacitance increase, and in some cells
      even failed to stimulate release, larger and more consistent responses were
      obtained with > or = four action potentials. 5. Comparison of the rates of
      exocytosis measured in response to depolarization, mobilization of Ca2+ from
      intracellular stores or infusion of Ca2+ through the patch pipette suggests that
      [Ca2+]i at the secretory sites attains a concentration of several micromolar.
      This is much higher than the average [Ca2+]i detected by microfluorimetry
      suggesting the existence of steep spatial gradients of [Ca2+]i within the B-cell.
      6. Inclusion of inhibitors of Ca2+/calmodulin-dependent protein kinase II in the
      intracellular solution reduced the depolarization-induced exocytotic responses
      suggesting this enzyme may be involved in the coupling between elevation of
      [Ca2+]i to stimulation of the secretory machinery. 7. The size of the unitary
      exocytotic event was 2 fF, corresponding to a secretory granule diameter of 250
      nm. 8. Over short periods, exocytosis may be extremely fast (1 pF/s or 500
      granules/s), which is much higher than the rate of endocytosis (18 fF/s or 9
      granules/s). Since the latter is in better agreement with the maximum rate of
      insulin secretion from islets (approximately 2 granules/s), we suggest that
      membrane retrieval may set an upper limit on the rate of exocytosis during
      extended periods of secretion.

PMID- 8145166
TI  - Potassium currents operated by thyrotrophin-releasing hormone in dissociated CA1
      pyramidal neurones of rat hippocampus.
AB  - 1. Membrane currents activated by thyrotrophin-releasing hormone (TRH) were
      investigated in the dissociated rat hippocampal CA1 pyramidal neurone using the
      nystatin perforated patch recording configuration. 2. Under current-clamp
      condition, TRH caused a transient hyperpolarization accompanied by a decrease of
      firing activity and a successive long-lasting depolarization. The latter induced
      a blockade of firing. 3. When neurones were held at a holding potential (VH) of 
      40 mV under voltage clamp, TRH elicited a transient outward current with an
      increase in the membrane conductance, which was followed by a sustained inward
      current with a decrease in membrane conductance. The inactive TRH metabolite, TRH
      free acid, did not induce any currents. 4. The reversal potential of TRH-induced
      outward current (ETRH) was close to the K+ equilibrium potential (EK). The change
      in ETRH for a 10-fold change in extracellular K+ concentration was 56.4 mV,
      indicating that the membrane behaves like a K+ electrode in the presence of TRH.
      On the other hand, the TRH-induced inward current was due to suppression of a
      slow inward current relaxation during hyperpolarizing voltage commands to -50 mV
      from a VH of -40 mV, indicating the suppression of the voltage- and time
      dependent component of the K+ current (M-current). 5. The TRH-induced outward
      current (ITRH) increased in a concentration-dependent manner over the
      concentration range 10(-8)-10(-6) M. The half-maximum concentration was 7.4 x 10(
      8) M and the Hill coefficient was 1.5. 6. The TRH-induced outward current (ITRH)
      was antagonized by K+ channel blockers such as tetraethylammonium (TEA), 4
      aminopyridine (4-AP) and Ba2+ in a concentration-dependent manner. ITRH was
      insensitive to both apamin and iberiotoxin. 7. The first application of TRH to
      neurones perfused with Ca(2+)-free external solution containing 2 mM EGTA could
      induce ITRH but the TRH response diminished dramatically with successive
      applications. Intracellular perfusion with a Ca2+ chelator, 1,2-bis(O
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), also diminished the TRH
      response. 8. The depletion of Ca2+ from the intracellular Ca2+ store by
      thapsigargin blocked the TRH response without affecting the caffeine response.
      Pretreatment with Li+ significantly enhanced ITRH, suggesting that ITRH is
      involved in the elevation of intracellular free Ca2+ released from the inositol
      1,4,5-trisphosphate (IP3)-sensitive Ca2+ store site but not from the caffeine
      sensitive one. 9. Staurosporine, a protein kinase C (PKC) inhibitor, suppressed
      ITRH in a concentration-dependent manner (the half-maximum inhibitory
      concentration (IC50), was 2.45 x 10(-8) M).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145167
TI  - Effects of membrane potential and muscarine on potassium M-channel kinetics in
      rat sympathetic neurones.
AB  - 1. Using cell-attached patch pipettes, sustained activity of single potassium M
      channels was recorded from dissociated rat superior cervical ganglion neurones.
      Previous results indicated that this activity, consisting of three main levels of
      open-channel conductance (congruent to 7, congruent to 12 and congruent to 19 pS)
      was activated by membrane depolarization and inhibited by muscarine added outside
      the patch. Consequently, a kinetic analysis was undertaken in order to identify M
      channel states sensitive to muscarine and membrane potential. 2. Channel activity
      recorded at 30 mV positive to the resting membrane potential level (congruent to 
      60 mV) showed three shut and two open times. Mean shut times were: tau s1 = 8.0
      +/- 2.2 ms; tau s2 = 71.3 +/- 8.6 ms and tau s3 = 740 +/- 220 ms. Mean open times
      were: tau o1 = 10.6 +/- 1.9 ms and tau o2 = 59.3 +/- 8.7 ms. When bursts of
      channel openings were determined as those including tau s1, two exponential
      components were evident in burst duration distributions (tau b1 = 11.0 +/- 0.9 ms
      and tau b2 = 80.4 +/- 11.0 ms). 3. Membrane hyperpolarization significantly
      lengthened all three shut times and shortened both open times. It also slightly
      enhanced the relative contribution of high-conductance channels and decreased the
      relative contribution of low-conductance channels to overall activity. 4. All
      three shut times of the M-channels were lengthened by 10 microM muscarine without
      significantly affecting their open times. 5. It is concluded that both open and
      shut states of the M-channel are voltage sensitive while only shut states are
      sensitive to muscarine.

PMID- 8145168
TI  - Mechanical determinants of gradient walking energetics in man.
AB  - 1. The metabolic cost and the mechanical work at different speeds during uphill,
      level and downhill walking have been measured in four subjects. 2. The mechanical
      work has been partitioned into the internal work (W(int)), due to the speed
      changes of body segment with respect to the body centre of mass (BCM), and the
      external work (W(ext)), related to the position and speed changes of the BCM in
      the environment. 3. W(ext) has been further divided into a positive part W+ext)
      and a negative one (W-(ext)), associated with the energy increases and decreases,
      respectively, over the stride period. 4. For all constant speeds the most
      economical gradient has been found to be -10.2% (+/- 0.8 S.D.). 5. At each
      gradient there is a unique W+ext/W-ext ratio (= 1 in level walking), regardless
      of speed, with a tendency for W-ext and W+ext to vanish above +15% and below -15%
      gradient, respectively. 6. W(int) is constant at each speed regardless of
      gradient. This is partly explained by an only slight decrease in stride frequency
      at increasing gradient. W(int) constancy implies that it has no role in
      determining the optimum gradient. 7. A linear multiple regression relating W+ext
      and W-ext to the metabolic cost at different gradients showed that negative (eff
      ) and positive (eff+) efficiencies decrease with increasing speed (from 0.912 to
      0.726, and from 0.182 to 0.146, respectively). The eff-/eff+ ratio, however,
      remains rather constant (4.995 +/- 0.125 S.D.). 8. We conclude that the measured
      W(ext), the W+ext/W-ext partitioning and eff-/eff+ ratio, i.e. the different
      efficiency of the muscles used as force and brake generators, can explain the
      metabolic optimum gradient at about -10%.

PMID- 8145169
TI  - Changes in the short- and long-latency stretch reflex components of the triceps
      surae muscle during ischaemia in man.
AB  - 1. In order to establish the afferent source responsible for the M1 and M2
      stretch reflex components of the voluntarily activated human triceps surae
      muscle, mechanical reflex testing was applied before and during ischaemic
      blockade of the lower limb. This procedure is known to affect large, fast
      conducting afferent fibres earliest, specifically Ia afferents arising from
      muscle spindle afferents. 2. It was found that both the M1 and M2 components were
      eliminated at the same time, at a point when the P40 peak in the somatosensory
      evoked potential, produced from stimulation of fast conducting peripheral
      afferents, was also abolished. This evidence indicates that both reflex
      components are mediated by information carried by muscle spindle Ia afferents. 3.
      The M1 component was selectively increased in the early stages of ischaemia. The
      M2 response did not increase during this period, but showed a tendency to reduce
      in amplitude. This effect may arise as the result of increased recruitment of
      motor units in the M1 component reducing the number of units available for
      activation in the M2 response. 4. These results do not support the view that the
      M2 reflex component of the triceps surae muscle is mediated by secondary afferent
      information, but indicate, rather, that both the M1 and M2 components are
      mediated by Ia afferent information acting on spinal pathways.

PMID- 8145170
TI  - Apnoea following normocapnic mechanical ventilation in awake mammals: a
      demonstration of control system inertia.
AB  - 1. Inhibition of inspiratory muscle activity from volume-related feedback during
      mechanical ventilation has been shown previously. To determine if this
      neuromechanical inhibition displays a memory effect, the duration of expiration
      immediately following cessation of mechanical ventilation was assessed in eight
      normal subjects. The subjects were passively mechanically ventilated via a nasal
      mask until the end-tidal CO2 (PET,CO2) was a minimum of 30 mmHg and inspiratory
      effort was no longer detected, as evidenced by stabilization of mouth pressure
      and disappearance of surface diaphragm EMG activity. The ventilator output was
      held constant at a mean tidal volume (VT) of 1.0 l and breath duration of 4.6 s
      and PET,CO2 was increased 1-1.5 mmHg/min (via increased inspired CO2 fraction,
      FI,CO2) until inspiratory muscle activity returned. The PET,CO2 at which
      activation first occurred was defined as the CO2 recruitment threshold (PCO2,RT).
      The mechanical ventilation protocol was repeated and the PET,CO2 increased 1-1.5
      mmHg/min until it was a mean of 1.1 mmHg above spontaneous PET,CO2 and 3.6 mmHg
      below PCO2,RT. After 4-6 min of mildly hypercapnic mechanical ventilation, the
      mechanical ventilation was terminated. 2. Following termination of mechanical
      ventilation, the duration of the subsequent apnoea was 14.6 +/- 2.8 s (mean +/-
      S.E.M.) or 453 +/- 123% > spontaneous TE and 178 +/- 62% > the TE chosen by the
      subject during 'assist control' ventilation at VT = 1.0 l. 3. To test the
      hypothesis that the apnoea following cessation of mechanical ventilation was due
      to a vagally mediated memory effect, the study was repeated in five double-lung
      transplant patients with similar PCO2,RT to normal subjects. These pulmonary
      vagally denervated patients also displayed an apnoea (14.5 +/- 4.0 s) upon
      cessation of mechanical ventilation (at a PET,CO2 2.0 mmHg > eupnoea and 2.4 mmHg
      < PCO2,RT), that was 367 +/- 162% > spontaneous TE. 4. We also found significant
      apnoea in the awake dog immediately following mildly hypercapnic passive
      mechanical ventilation, and this was similar before and after bilateral vagal
      blockade (15.7 +/- 1.3 and 19.7 +/- 4.7 s, respectively). 5. We conclude that
      neuromechanical inhibition of inspiratory muscle activity, produced by passive
      mechanical ventilation at high VT, exhibits a memory effect reflected in TE
      prolongation, which persists in the face of substantial increases in
      chemoreceptor stimuli. This effect is not dependent on vagal feedback from lung
      receptors. 6. We hypothesize that this persistent apnoea represents an inherent
      'inertia', characteristic of the ventilatory control system.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8145171
TI  - Reflex responses to stimulation of mechanoreceptors in the left ventricle and
      coronary arteries in anaesthetized dogs.
AB  - 1. Previous work has shown that physiological increases in mean aortic root
      pressure, which change the pressure in both the coronary circulation and the left
      ventricle, result in reflex vasodilatation. This study was undertaken to attempt
      to localize the reflexogenic area mainly responsible for the reflex. 2. In
      anaesthetized, artificially ventilated dogs, cannulae connected to perfusion
      systems were inserted in the ascending aorta, left ventricular apex and left
      atrium. This allowed us to change the pressures in: (a) the aortic root including
      both the coronary arteries and the left ventricle; (b) aortic root and coronary
      arteries, at constant ventricular pressure; and (c) in the ventricle, with mean
      (although not pulse) aortic pressure constant. Aortic and carotid baroreceptors
      were perfused at constant pressure and reflex responses were determined from
      changes in perfusion pressures (flows constant) to a vascularly isolated hindlimb
      and to the remainder of the systemic circulation. 3. Combined changes in mean
      aortic root (coronary arterial) and ventricular systolic pressures consistently
      resulted in decreases in perfusion pressures. A change in only mean aortic root
      (coronary arterial) pressure, with ventricular pressure constant, also resulted
      in decreases in perfusion pressures and these were only a little smaller than
      those to the combined stimulus. Changes in ventricular systolic pressure resulted
      in responses averaging only about 30% of those to the combined stimulus. 4.
      Setting mean aortic root or ventricular systolic pressures at different levels
      did not affect the responses to changes in pressures in the other region. 5.
      These results show that physiological increases in pressure in the aortic root
      and coronary arteries, in the absence of changes in pressure in the left
      ventricle, cause reflex vasodilatation. The relatively small response occurring
      when ventricular pressure was changed could be due either to a contribution from
      ventricular receptors or to a change in the stimulus to coronary receptors
      resulting from changes in the ventricular or aortic pulse. 6. We conclude that
      the reflex effects of increases in mean aortic root pressure are due mainly to
      stimulation of coronary arterial baroreceptors.

PMID- 8145172
TI  - Afferent discharges from coronary arterial and ventricular receptors in
      anaesthetized dogs.
AB  - 1. Previous work has shown that increases in aortic root pressure result in
      reflex vasodilation, and that this response is likely to result mainly from
      stimulation of receptors in the coronary arteries, although contribution from
      left ventricular receptors was not excluded. This investigation was undertaken to
      resolve this question and to determine the afferent nerve fibres likely to be
      involved in this reflex. 2. In chloralose-anaesthetized dogs a perfusion circuit
      was used which allowed us to change the pressures in: (a) the aortic root,
      coronary arteries and the left ventricle; (b) aortic root and coronary arteries
      at constant ventricular pressure; and (c) the left ventricle with mean (although
      not pulse) aortic pressure constant. Electrophysiological recordings were made
      from slips dissected from the vagus nerve which responded with an increase in
      discharge to either combined increases in the pressures, or to aortic root
      injections of veratridine. 3. Recordings were made from twenty-one vagal
      afferents. On the basis of their conduction velocities, eleven were classified as
      non-myelinated and ten as myelinated. 4. Three non-myelinated afferents responded
      to veratridine injections only, three to both veratridine and combined aortic
      root and ventricular pressure changes, and five to pressure changes only.
      Responses to pressure occurred only when ventricular systolic pressure exceeded
      30 kPa. 5. None of the myelinated afferents responded to veratridine. All showed
      increases in discharge to combined increases in mean aortic root, coronary
      arterial and left ventricular systolic pressures, which would be graded over a
      range similar to that which caused reflex changes. All were more sensitive to
      changes in mean coronary pressure than to changes in ventricular systolic
      pressure. 6. We conclude that myelinated vagal afferent nerve fibres, which
      respond predominantly to changes in mean coronary arterial pressure, are likely
      to be responsible for the vasodilation to the changes in mean aortic root
      pressure previously reported. These fibres are probably attached to coronary
      arterial mechanoreceptors.

PMID- 8145173
TI  - A chloride current associated with swelling of cultured chick heart cells.
AB  - 1. Cultured chick heart cells challenged by hyposmotic stress underwent
      regulatory volume decrease (RVD) that was attenuated by prior depletion of
      intracellular chloride. 2. During hyposmotic swelling, cell aggregates
      experienced an initial increase in spontaneous contractile activity followed by
      eventual quiescence. Conventional microelectrode studies revealed an underlying
      increase in spontaneous electrical activity, followed by a sustained
      depolarization beyond threshold. 3. Whole-cell patch clamp studies, with K+
      currents blocked, indicated that exposure of cells to hyposmotic solution (NaCl
      reduction) resulted in a rapid osmotic swelling followed by a substantial
      increase in whole-cell conductance which persisted for the duration of hyposmotic
      exposure and was almost completely reversed on return to isosmotic bath solution.
      4. For a variety of Cl- concentrations, the reversal potentials (Erev) of the
      measured swelling-activated current closely followed the calculated Cl-
      equilibrium potential (ECl) with a linear regression slope of 0.82. When
      estimated by the Nernst equation, the relationship between Erev and the [Cl
      ]i/[Cl-]o ratio fitted well with a slope of 51 mV per decade change in the
      concentration ratio, consistent with a Cl(-)-selective conductance. 5. The
      permeability ratios of this swelling-activated conductance to chloride,
      methanesulphonate (MSA) and aspartate (Asp) were calculated as PCl:PMSA:PASP =
      1:0.36:0.02, with the ion selectivity sequence of Cl- > MSA- >> Asp-, which
      suggests the swelling-activated conductance is slightly permeable to other
      anions. 6. Application of a Cl- channel blocker, diphenylamine-2-carboxylate
      (DPC, 200 microM), substantially suppressed the swelling-activated current
      without shifting the Erev of this current. The effect of DPC was independent of
      membrane potential. 7. This evidence demonstrates that hyposmotic swelling of
      cultured chick heart cells activates a channel-mediated Cl- conductance which may
      be associated with the integrated response of volume-regulatory mechanisms.

PMID- 8145174
TI  - Ions required for the electrogenic transport of GABA by horizontal cells of the
      catfish retina.
AB  - 1. Solitary horizontal cells were isolated from catfish retinas. Membrane
      currents activated by extracellular and intracellular GABA were characterized
      during a whole-cell voltage clamp. 2. Extracellular GABA activated two currents:
      a GABAA current, and an 'influx' current mediated by a GABA transporter. The
      influx current was studied after the GABAA current was blocked with 0.5 mM
      picrotoxin. The influx current required extracellular Na+ and Cl-. Extracellular
      Na+ could not be replaced by another alkali metal cation. 3. The influx current
      also depended upon the identity of ions in the intracellular solution. Either an
      intracellular alkali metal cation or Cl- was required to produce an influx
      current. 4. The influx current was inward at -75 mV and decreased as the membrane
      was depolarized towards +20 mV. When the membrane was depolarized beyond +25 mV,
      the polarity of the current depended upon the ion composition of the
      intracellular solution and could be inward, zero or outward. 5. The introduction
      of GABA into a cell during the course of an experiment produced an outward
      current. This 'efflux' current was small at -75 mV and increased with
      depolarization. The efflux current required intracellular Na+ and Cl-.
      Intracellular Na+ could not be replaced by another alkali metal cation. 6. The
      efflux current also depended upon the identity of ions in the extracellular
      solution. An extracellular alkali metal cation was required to produce an efflux
      current. Removing extracellular Cl- did not affect the efflux current. 7. The
      outward movement of GABA produced a local accumulation in extracellular GABA
      concentration that could be detected by the activation of the GABAA current. GABA
      efflux only occurred during conditions that produced an efflux current.
      Electroneutral efflux did not occur. 8. In the absence of GABA, extracellular
      alkali metal cations produced a 'leakage' current. The leakage current was inward
      at -75 mV and decreased as the membrane was depolarized towards +20 mV. When the
      membrane was depolarized beyond +25 mV, the polarity of the leakage current
      depended, like the GABA influx current, upon the ion composition of the
      intracellular solution and could be inward, zero or outward. The addition of GABA
      to the intracellular solution produced an efflux current and suppressed the
      leakage current. 9. We conclude that the transporter mediates electrogenic
      influx, efflux and leakage. Each mode of operation depends upon ions on both
      sides of the membrane. Influx and efflux are not symmetrical.

PMID- 8145175
TI  - Maintenance drug therapy of panic disorder.
AB  - The efficacy of tricyclics and benzodiazepines in the short term (approximately 2
      4 months) treatment of panic disorder is well demonstrated, but efficacy over the
      longer term is not considered established. The present study provided systematic
      data from a double blind comparison of maintenance therapy (up to 8 months) of
      panic disorder with or without agoraphobia with alprazolam, imipramine, or
      placebo in 181 patients who had responded to the same regimen in a randomized 8
      week treatment trial. All three groups had improved during the first 2 months
      (active treatments more than placebo and about equal to each other), and all
      maintained or extended their improvement over the next 6 months without any
      significant change in dose. More than twice as many alprazolam and imipramine
      than placebo patients (15%) remained in treatment for the full 8 months and did
      slightly better on symptom measures than the remaining placebo patients. Both
      medications were well tolerated during the maintenance period. The data suggest
      sustained efficacy and safety of imipramine and alprazolam over an extended
      period. More specifically, they suggest that tolerance does not develop to the
      therapeutic effects of either drug.

PMID- 8145176
TI  - Discontinuation reactions to alprazolam in panic disorder.
AB  - Panic disorder is a chronic illness with only some degree of spontaneous
      recovery. It is not surprising therefore that discontinuation of an effective
      medical treatment may be followed by relapse. Therefore the timing and
      methodology of discontinuing that treatment are now recognized as essential
      facets of optimal clinical management. In addition to relapse, rebound and the
      withdrawal syndrome have been reported with many psychotropic agents,
      particularly with the benzodiazepines. This paper discusses data from three
      discontinuation studies with alprazolam i.e. the Phase I Cross-National
      Collaborative Panic discontinuation study after short-term treatment, the Phase I
      discontinuation study after long-term treatment, and data from the Montreal site
      of the Alprazolam SR discontinuation study. Phase I of the Cross-National
      Collaborative Study of Panic Disorder investigated the discontinuation of
      alprazolam in two populations. There was an intensive, placebo-controlled, time
      limited study of discontinuation after short-term treatment (8 weeks) in the
      first population. For the second, there was a less rigorous open follow-up of
      patients who had been treated for 5-12 months with alprazolam. The dose-reduction
      regimen of alprazolam in both studies was approximately the same--a 1 mg decrease
      every 3-7 days. In the short-term treatment study, 109 patients were treated for
      8 weeks, tapered for 4 weeks and observed for another 2 weeks post
      discontinuation. Significant relapse in the alprazolam-treated group occurred
      during discontinuation. Rebound of panic attacks occurred in 27% of patients
      given alprazolam, and distinct transient withdrawal syndrome occurred in 35%.
      Indicative of the withdrawal syndrome were confusion, clouded sensorium,
      heightened sensory perception, dysosmia, paresthesias, muscle cramps, muscle
      twitch, blurred vision, diarrhea, decreased appetite, and weight loss. The
      clinical course in the alprazolam-treated patients revealed a marked exacerbation
      of symptoms during the end of the tapering period and the first week without
      medication, which was followed by improvement during the second post-taper week.
      In the long-term treatment study, 142 patients were treated with alprazolam for
      periods ranging from 5 months to 1 year (mean, 27.5 weeks). In this naturalistic
      study, 76% of the patients reported improvement, 6.3% reported no change, and
      10.6% reported that they were worse. During discontinuation, 12.8% of the 128
      patients whose dosage was tapered reported some kind of nonspecified withdrawal
      symptoms. Of the 142 patients, 47.2% were able to taper their medication dosage
      and to discontinue treatment; 19.7% tapered but restarted alprazolam shortly
      after discontinuation; 33.1% were unable or unwilling to taper or discontinue
      alprazolam.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145177
TI  - Cognitive treatment for panic disorder.
AB  - Several kinds of evidence indicate that there are important psychological causes
      of panic disorder as well as the biological causes that have been demonstrated by
      others. These psychological causes are fears that physical symptoms of anxiety
      will be followed by an immediate medical emergency: for example, that
      palpitations will be followed by a heart attack. Evidence is presented to show
      (a) that such fears are more frequent among panic disorder patients than other
      anxious patients; (b) that activating the fears can produce panic; and (c) that
      reducing the fears can attenuate the effects of procedures that produce panic.
      For panic disorder, cognitive therapy, which reduces these specific fears, gives
      results comparable to those of imipramine and alprazolam. If further research
      confirms that these therapeutic effects of cognitive therapy are sustained well
      beyond the end of treatment, cognitive therapy could be the treatment of choice
      for panic disorder.

PMID- 8145178
TI  - The effects of alprazolam on corticotropin-releasing factor neurons in the rat
      brain: implications for a role for CRF in the pathogenesis of anxiety disorders.
AB  - Considerable evidence indicates that corticotropin-releasing factor (CRF) is
      responsible for integrating not only the endocrine, but the autonomic and
      behavioral responses of an organism to stress. We have investigated the effects
      of the anxiolytic triazolobenzodiazepine, alprazolam, on the activity of the
      hypothalamic-pituitary-adrenal (HPA) axis and of CRF neurons following acute and
      chronic administration. In addition, because many of the signs and symptoms
      observed in animals and humans following abrupt discontinuation of
      benzodiazepines resemble those of the stress response, we examined the effect of
      alprazolam withdrawal on CRF neurons and HPA axis activity. Alprazolam decreases
      CRF concentrations in the locus coeruleus 0.5-3.0 hours following acute
      injection. Similarly, chronic (14 days) alprazolam administration also results in
      decreased CRF concentrations in the locus coeruleus. CRF concentrations return to
      control values 24 hours following abrupt alprazolam withdrawal. Moreover, abrupt
      alprazolam withdrawal results in increased plasma ACTH and corticosterone
      concentrations and decreased anterior pituitary CRF receptor concentrations 24
      hours following drug discontinuation. Thus, abrupt alprazolam withdrawal
      profoundly activates the HPA axis. These indices of HPA axis activity return to
      control values by 48 hours post-withdrawal. These actions of alprazolam on CRF
      neurons are opposite to those observed following acute or chronic stress. These
      results support the hypothesis that CRF-containing neurons innervating the locus
      coeruleus may be involved in the pathogenesis of anxiety, and in the actions of
      clinically efficacious anxiolytics.

PMID- 8145179
TI  - The NIMH Research Program in Panic Disorder: the present and future.

PMID- 8145180
TI  - Comorbidity of panic and major depressive disorder.
AB  - The objective of this report is to determine whether those patients with panic
      disorder who have current major depression disorder (MDD) differ from those who
      do not in terms of demographics, comorbid disorders, severity of illness, nature
      of symptoms of panic attacks and psychosocial functioning. The sample consisted
      of 182 patients with current or history of panic disorder measured by
      standardized interview techniques. For analysis these patients were then divided
      by presence or absence of current MDD. The two groups were not different in age,
      sex, or marital status, age of onset, or symptom characteristics of panic
      attacks. However, patients with MDD were more likely to have Social Phobia and
      Generalized Anxiety Disorder, been hospitalized, made suicide attempts or
      gestures, have poorer psychosocial functioning, and currently be experiencing
      panic with more severe symptoms. These findings are discussed in terms of
      previous literature in the area.

PMID- 8145181
TI  - The classification of panic disorders: from Freud to DSM-IV.
AB  - The authors trace the history of the classification of anxiety disorders,
      beginning with a detailed discussion of Freud's work on anxiety-neurosis as a
      basis for subsequent work. They discuss how anxiety disorders were described in
      DSM-I and DSM-II where Freud's concept of the anxiety neurosis was used as a
      major organizing principle. The revolutionary change in DSM-III is described in
      which the term and organizing principle of neurosis was dropped. The
      controversies that have arisen as a result of changes in DSM-III-R are discussed,
      particularly as they relate to compatibility with the International
      Classification of Diseases-10 (ICD-10) and especially with respect to the
      relationship and priority of panic and agoraphobia. Finally the authors discuss
      the process by which decisions will be made in DSM-IV where changes will be based
      on systematic reviews of empirical evidence whenever possible.

PMID- 8145182
TI  - Panic disorder in cardiology patients: a review of the Missouri Panic/Cardiology
      Project.
AB  - This paper reviews current evidence from several cardiology populations that
      suggests that panic disorder is prevalent and underdiagnosed. Cardiology patients
      with atypical angina, and no heart disease have a high likelihood of having panic
      disorder, as suggested by studies of two separate cardiology populations. That
      they resemble psychiatric populations with panic is suggested by their positive
      response to alprazolam. A panic disorder subtype, called non-fear panic disorder
      also appeared in about one-third of these cardiology panic patients. These
      patients have most of the panic symptoms but do not report fear during their
      episodes.

PMID- 8145183
TI  - Epidemiology of panic disorder: progress and unresolved issues.
AB  - Recent epidemiological studies have consistently shown that panic disorder,
      according to DSM-III, occurs in adults with a lifetime prevalence of about 2% and
      a 6-month prevalence of about 1.2%. Panic attacks are relatively common, with a
      lifetime rate of about 9%. Being female and divorced and separated is associated
      with higher prevalence of panic disorder. The hazard rates for panic disorder
      were highest between the ages of 25 and 34 years for females and between the ages
      of 30 and 44 years for males. Panic disorder frequently co-occurs with other
      anxiety disorders as well as with a wide range of mental disorders such as
      depression and substance use disorder. Based on few epidemiological studies,
      panic disorder has been found to have a chronic course with rare complete
      remission. Subjects with panic disorder were at an increased risk of social
      impairment, not getting along with their partners, as well as being financially
      dependent, and were likely to report fair or poor global physical health, and
      emotional health. Cases with panic disorder had the most severe psychosocial
      impairment and the worst outcome as compared to other anxiety disorders.
      Moreover, they are high users of all types of medical services, including mental
      health and general medical providers. Although recent epidemiological data, with
      its improved methodology, have considerably increased our knowledge concerning
      panic attack, panic disorder and agoraphobia, there are still major questions
      concerning the etiology, natural history, prevention, or control of panic
      disorder that need to be answered. Furthermore, since panic disorder has been
      considered as developing in stages, our current epidemiological knowledge cannot
      tell us in sufficient detail about the specific role of suggested risk factors in
      the development of panic disorder through its various stages.

PMID- 8145184
TI  - Family genetic studies of panic disorder.
AB  - A review of family and twin studies using specified diagnostic criteria shows the
      highly familial nature of panic disorder and suggests evidence for a genetic
      etiology. The population-based lifetime rates of panic disorder cross-nationally
      range between 1.2/100 and 2.4/100, whereas, the lifetime rates in first-degree
      relatives of panic probands range between 7.7/100 and 20.5/100. There is evidence
      from family and twin studies for the separation of panic disorder and generalized
      anxiety disorder. While there is a substantial comorbidity in individuals between
      panic disorder and major depression, these two disorders are separate conditions
      which are independently and specifically transmitted within families. The mode of
      transmission of panic disorder remains unclear. The high lifetime rates of panic
      disorder, strong evidence for vertical transmission, and the potential biological
      markers have increased interest in the application of modern linkage techniques.
      Several genetic linkage studies of panic disorder are ongoing.

PMID- 8145185
TI  - A controlled family study in panic disorder.
AB  - There are only a few family studies in panic disorder. Although there is some
      evidence that panic disorder is familial, the exact figures of the familial risk
      for this disorder are at variance across different studies; the impact of
      comorbidity and of the gender of relatives is also unclear. Family studies in
      panic disorder controlling for the comorbidity in probands are therefore
      indicated. This study presents the morbid risks in families of 40 "pure" panic
      disorder probands (DSM-III-R) without a history of psychotic disorders, major
      depression or alcoholism compared with families of 80 controls recruited in the
      general population. The relative frequency of panic disorder (DSM-III-R) in the
      first-degree relatives of panic disorder probands was 5.7% (the age corrected
      morbid risk is 7.9%) compared to 1.8% in relatives of healthy controls (age
      corrected morbid risk 2.3%). Agoraphobia segregated predominantly among female
      relatives of agoraphobic probands. An increased familial risk of major depression
      and of alcoholism was also observed. Comorbidity with alcoholism and major
      affective disorders was excluded in panic disorder probands by definition;
      therefore, these findings indicate that the etiological factors underlying panic
      disorder may overlap with those of alcoholism and those of unipolar major
      depression.

PMID- 8145186
TI  - The African wave-type electric fish, Gymnarchus niloticus, lacks corollary
      discharge mechanisms for electrosensory gating.
AB  - Gymnarchus niloticus, a wave-type African electric fish, performs its jamming
      avoidance response by relying solely upon afferent signals and does not use
      corollary discharges from the pacemaker nucleus in the medulla which generates
      the rhythmicity of electric organ discharges. This is in sharp contrast to the
      mode of sensory processing found in closely related African pulse-type electric
      fishes where afferent signals are gated by corollary discharges from the
      pacemaker for the distinction of exafferent and reafferent stimuli. Does
      Gymnarchus still possess a corollary discharge mechanism for other behavioral
      tasks but does not use it for the jamming avoidance response? In this study, I
      recorded from and labeled medullary neuronal structures that either generate or
      convey the pacemaker signal for electric organ discharges to examine whether this
      information is also sent directly to any sensory areas. The pacemaker nucleus was
      identified as the site of generation of the pacemaking signal. The pacemaker
      neurons project exclusively to the lateral relay nucleus which, in turn projects
      exclusively to the medial relay nucleus. Neurons in the medial relay nucleus send
      unbranched axons to the spinal electromotoneurons. These neurons are entirely
      devoted to drive the electric organ discharges, and no axon collaterals from
      these neurons were found to project to any sensory areas. This indicates that
      Gymnarchus does not possess the neuronal hardware for a corollary discharge
      mechanism.

PMID- 8145187
TI  - Sleep and cortical temperature in the Djungarian hamster under baseline
      conditions and after sleep deprivation.
AB  - The Djungarian hamster (Phodopus sungorus) is a markedly photoperiodic rodent
      which exhibits daily torpor under short photoperiod. Normative data were obtained
      on vigilance states, electroencephalogram (EEG) power spectra (0.25-25.0 Hz), and
      cortical temperature (TCRT) under a 16:8 h light-dark schedule, in 7 Djungarian
      hamsters for 2 baseline days, 4 h sleep deprivation (SD) and 20 h recovery.
      During the baseline days total sleep time amounted to 59% of recording time, 67%
      in the light period and 43% in the dark period. The 4 h SD induced a small
      increase in the amount of non-rapid eye movement (NREM) sleep and a marked
      increase in EEG slow-wave activity (SWA; mean power density 0.75-4.0 Hz) within
      NREM sleep in the first hours of recovery. TCRT was lower in the light period
      than in the dark period. It decreased at transitions from either waking or rapid
      eye movement (REM) sleep to NREM sleep, and increased at the transition from NREM
      sleep to waking or REM sleep. After SD, TCRT was lower in all vigilance states.
      In conclusion, the sleep-wake pattern, EEG spectrum, and time course of TCRT in
      the Djungarian hamster are similar to other nocturnal rodents. Also in the
      Djungarian hamster the time course of SWA seems to reflect a homeostatically
      regulated process as was formulated in the two-process model of sleep regulation.

PMID- 8145188
TI  - Encoding of phase spectra by the peripheral auditory system of the bullfrog.
AB  - In this study we have examined the sensitivity of auditory nerve fibers in the
      bullfrog (Rana catesbeiana) to changes in the phase spectrum of an equal
      amplitude multi-harmonic stimulus which spanned the bullfrog's range of hearing.
      To assess peripheral auditory phase sensitivity, changes in the response
      properties of VIIIth nerve fibers were measured when the relative phase angle of
      a single harmonic component nearest a unit's best excitatory frequency was
      systematically varied. The results revealed that shifts in the phase spectrum are
      encoded in at least 3 different ways by the peripheral auditory system of the
      bullfrog: 1) by changes in the degree of spike synchronization of fibers from
      both inner ear organs (the amphibian papilla and the basilar papilla) to the
      fundamental waveform period; 2) by changes in the shapes of period histograms of
      fibers from both organs; and 3) by changes in the spike rates of amphibian
      papilla fibers. The presence of phase sensitivity in the peripheral auditory
      system of the bullfrog indicates that information regarding the fine-temporal
      waveshape and the underlying phase spectrum of an acoustic signal is contained
      within the spike trains of VIIIth nerve fibers. Similar sensitivities to changes
      in the phase spectra and temporal waveshapes of acoustic signals may also be
      present in the peripheral auditory system of other vertebrates. Such studies
      could provide valuable insight into the role that phase spectra and temporal
      waveshape may play in bioacoustic communication.

PMID- 8145189
TI  - Sound production evoked by electrical stimulation of the forebrain in the oyster
      toadfish.
AB  - In mammals, birds and amphibians the neural pathways controlling sound production
      descend from higher centers in the forebrain, whereas in fishes only brainstem
      and spinal centers have been explicitly implicated in sound production. We now
      report that electrical stimulation of the forebrain of the oyster toadfish
      (Opsanus tau) readily evokes both the agonistic grunt and the courtship
      boatwhistle. Boatwhistles are more realistic than ones previously evoked from
      lower centers. Positive stimulation sites are localized in the preoptic area
      (nucleus preopticus parvocellularis anterior) and the supra-commissural nucleus
      of the ventral telencephalon, a likely homologue of the amygdala. Both sites
      contain gonadal steroid-concentrating neurons and play a central role in fish
      courtship behavior. Evoked sounds form a continuum from knock grunts, burst
      grunts, transition boatwhistles to complete boatwhistles; sound pressure level
      (SPL), fundamental frequency and duration increase consistently within the
      continuum. For all sound types, SPLs exhibit the smallest variation (coefficients
      of variation of 2.7 to 5.7%), fundamental frequency is intermediate (5 to 13%)
      and durations vary most widely (18 to 60%). Boatwhistles, with the smallest
      variation and greatest amplitude, are likely generated by a maximal output of the
      CNS and sonic muscles. Grunt SPLs however, vary over a range of 26 dB for all
      fish and by as much as 18 dB in an individual; suggesting recruitment of variable
      numbers of motor units despite electrical coupling within the sonic motor
      nucleus.

PMID- 8145190
TI  - Effects of scaphognathite nerve stimulation on the acutely deafferented crab
      ventilatory central pattern generator.
AB  - 1. Sensory axons from crab (Carcinus maenas) scaphognathites enter the thoracic
      ganglion primarily via the LNb branch of the levator nerve. The LNa branch of the
      levator nerve and the depressor nerve each contain relatively few sensory axons.
      2. Acutely deafferented ventilatory central pattern generators show a free
      running burst rate which is lower than that observed in intact crabs. Electrical
      stimulation of the levator nerve, or of its LNb branch, increases the burst rate
      in a frequency dependent manner. Stimulation at high enough intensity to recruit
      afferents will restart a paused motor rhythm. Stimulation of the levator nerve
      with short pulse trains phase resets and can entrain the rhythm. 3. In addition
      to increasing the burst rate, LNb stimulation also causes a progressive
      elimination of motor neurons from the bursts as the stimulating frequency
      increases, probably due to depolarization of the 3 oval organ 'giant' afferent
      axons in this branch. Intracellular depolarization of single oval organ afferents
      will also inhibit some motor neurons as well as slow or stop the rhythm. 4.
      Continuous stimulation of the depressor nerve does not affect the ganglionic
      burst rate and this nerve contains only a few small diameter afferent axons;
      however, brief trains of stimuli can reset the rhythm in a phase-dependent
      manner.

PMID- 8145191
TI  - Degeneration of afferent neurons and long-term stability of the ventilatory
      central pattern generator in chronically deafferented crabs.
AB  - 1. The effects of chronic deafferentation, 3-180 days, are tested on the function
      and morphology of the crab (Carcinus maenas) ventilatory central pattern
      generator (CPGv). Almost all afferent axons are carried in the mixed
      sensory/motor levator nerve. The ability to speed the CPGv cycle rate by
      stimulating this nerve (Wilkens and DiCaprio 1994) decreases as the afferent
      neurons degenerate. Stimulation of the levator nerve eliminates motor units from
      the output even after 60 days of deafferentation, similar to the effects seen in
      acute preparations. 2. The 3 oval organ afferent axons of the levator nerve have
      central somata and survive scaphognathectomy. Impulses carried by these axons are
      known to inhibit the CPGv in acutely deafferented preparations and they are
      believed to be responsible for the persistent inhibition following small afferent
      degeneration seen here. 3. After 6 months of deafferentation the motor neuron
      collateral arborization densities within the thoracic ganglia are reduced, but
      all motor neurons appear to survive. These long-term deafferented CPGvs generate
      accurate motor patterns at similar rates to the control CPGv, but at reduced
      intraburst spike frequency. The crab CPGv is quite stable following chronic
      deafferentation.

PMID- 8145192
TI  - Modulation of K(+)-channels in p-neurones of the leech CNS by phosphorylation.
AB  - Two types of potassium channels of identified (p-) neurones of the leech (Hirudo
      medicinalis) were investigated by using the patch-clamp technique. The open-state
      probability of these channels in cell-attached patches can be reduced by addition
      of 5-hydroxytryptamine to the bath solution. After excising the patches the
      application of alkaline phosphatase to the cytosolic face of the patch increases
      the open probability. The 5-HT1A-receptor agonist buspirone mimics the effect of
      5-HT. Our experiments show that the effect of 5-HT might be due to a channel
      phosphorylation via a 5-HT1A-receptor subtype.

PMID- 8145193
TI  - Psychiatric nursing in an era of change.
AB  - 1. A critically important question we must ask ourselves is: Are we equipped to
      handle the challenges and fully exploit the new opportunities that are ahead? To
      do this, we must manage change more effectively. 2. We need to restructure our
      whole system of education. The time has come to settle the issue of entry into
      practice and to establish one statutorily defined nurse that everybody will know
      as the American nurse, without any need to qualify the definitions. 3. Managing
      change and managing to change require effective leadership; that is, the
      capability to monitor, facilitate, and enhance communication and negotiation
      across boundaries. Boundaries include those of role, race, age, social status,
      sexual orientation, and other characteristics that differentiate. These
      characteristics, however, enrich and liven the discourse among us.

PMID- 8145194
TI  - The concept of guilt.
AB  - 1. Guilt is an uncomfortable feeling resulting from the commission or
      contemplation of a specific act contrary to one's internalized standards of
      conduct; it requires reparative action for the harm done to another to alleviate
      the uncomfortable feeling (distress). 2. The terms guilt and shame often are used
      interchangeably, but psychologic theory and phenomenologic studies clearly
      indicate that these are distinctly different affective experiences. Shame arises
      from the self's negative evaluation of the self (an evaluation that may or may
      not have been instigated by actual public exposure); guilt arises from the self's
      negative evaluation of specific behaviors or transgressions. 3. The psychiatric
      nurse is in an excellent position to intervene effectively with clients who are
      struggling with the emotional effects of guilt, and the psychiatric nurse can be
      instrumental in breaking the lifelong cycle of dysfunctional guilt feelings.

PMID- 8145195
TI  - An ethical dilemma: risk versus responsibility.
AB  - 1. In the psychiatric community, two highly profitable diagnoses currently are
      filling psychiatric hospitals: dissociative disorder and multiple personality
      disorder. Certainly these patients need help, and psychiatric nurses are well
      qualified to plan their scope of care. However, when the hospital reported on in
      this article exploited these diagnoses by encouraging practices that extended
      lengths of stay and restricted patient's rights, the nurses were forced to speak
      out as advocates for the patients. 2. The dissociative disorder unit housed 10
      patients billed at an intensive care unit rate of $1,200 per day. One patient's
      average fee per day was $1,560; multiply this by 10 patients, and the hospital
      received $15,600 per day from this unit alone. 3. Financial calculation is not
      what nurses are used to thinking about; indeed, it somehow seems unbefitting to
      link nursing care with any mention of monetary gain. Yet, this is exactly the
      sort of information that nurses must have in order to understand how hospital
      politics may influence their situation.

PMID- 8145196
TI  - Smoking health risk. Counseling of psychiatric patients.
AB  - 1. Cigarette smoking has been identified as the single most important source of
      preventable morbidity and premature mortality in the United States for each of
      the past 25 years. Despite a smoking rate of 50% to 84%, persons with psychiatric
      illness have not been the target of any documented smoking health risk education
      in current literature. 2. Most nurses view smoking health risk education as a
      nursing function, but few actually provide this care for patients due to
      perceived ineffectiveness of health risk education, belief that smoking is not a
      health risk, and lack of knowledge base to provide the care. 3. Data from the
      study reported on in the article reflected that nurses were providing smoking
      health risk information to less than 50% of patients. Nurses were not identifying
      nicotine dependence as a nursing problem and therefore were making no plans to
      provide nursing interventions to resolve it.

PMID- 8145198
TI  - Screening identifies individuals with untreated depression.

PMID- 8145197
TI  - Inspiring hope in the oncology patient.
AB  - 1. Cancer is a life-threatening disease that creates an uncertain and foreboding
      future, yet it is because of this uncertain future that hopes can be
      accommodated. 2. Inspiring hope is an intervention that can be used with many
      nursing diagnoses, especially when feelings of helplessness, hopelessness,
      powerlessness, and depression are present. 3. Most individuals are "hoping" ones,
      but at times the hoping process must be assisted. 4. The nurse can inspire hope
      by understanding the hoping process; offering nursing encouragement; and
      incorporating such skills as presence, touch, active listening, reality
      surveillance, and values clarification.

PMID- 8145199
TI  - A renewed sense of self.

PMID- 8145200
TI  - The role of insulin-like growth factors and epidermal growth factor-related
      peptides in intraovarian regulation in the pig ovary.
AB  - The autocrine and paracrine role of the insulin-like growth factors (IGFs) and
      epidermal growth factor (EGF)-related peptides in pig ovary are reviewed. For
      convenience, each of these regulatory systems is divided into several interactive
      components: regulated expression of the growth factors, growth factor reception
      at the cell surface and intracellular action of the growth factors. In addition,
      the concept of regulated bioavailability and targeting of growth factors in the
      extracellular space is developed as an important control locus and area for
      future study. With regard to the IGF system, these components include two ligands
      -IGF-I and -II, both expressed in the porcine ovary--and the possibility of three
      receptors. IGF-I and the type I IGF receptor appear to be the most important in
      stimulating ovarian function and amplifying hormone action. In addition, the 'set
      point' of the ovarian IGF system may be determined by the activity of several IGF
      binding proteins (IGFBPs). At least four of these proteins are expressed in the
      pig ovary. Studies of their regulation and action in ovarian cells indicate that
      they can function as antagonists to FSH and the IGFs. However, preliminary
      evidence suggests a more dynamic model in which these proteins may direct the
      site and timing of IGF effects. There are fewer data on the EGF system. At least
      four EGF-related peptides are expressed in pig ovaries, but insufficient
      information is available to predict their physiological regulation. These
      peptides are potent mitogens for ovarian cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145201
TI  - Sources and biological actions of relaxin in pigs.
AB  - Although the major source of relaxin in pigs is the corpus luteum of pregnancy,
      there is now evidence for relaxin gene expression and translation into protein in
      the theca interna cells of the preovulatory follicle, the corpus luteum of the
      cycle and the uterus. The theca interna cells retain their ability to express the
      relaxin gene and protein following ovulation. During the early stages of
      development of the corpus luteum, the theca-derived small lutein cells are the
      source of the relaxin transcript. As the corpus luteum becomes fully functional,
      there is a switch in the site of relaxin synthesis from small theca-derived
      lutein cells to large granulosa-derived cells. In the absence of luteolysis, this
      switch is accompanied by a dramatic rise in relaxin synthesis. Relaxin has been
      identified in boar seminal plasma and can maintain or increase sperm motility.
      However, a source of relaxin in the boar has not been identified. Relaxin is an
      important regulator of uterine function during pregnancy acting systemically to
      suppress myometrial activity and promote cervical dilation at parturition. The
      changes in thecal relaxin production during follicle development and its ability
      to promote growth and changes in proteolytic enzyme activity of granulosa cells
      in vitro have led to the concept of an autocrine or paracrine role for relaxin
      within the follicle. Uterotrophic effects of relaxin have been reported in
      rodents and swine and support the hypothesis that relaxin promotes uterine growth
      and expansion in early pregnancy to accommodate the growing fetuses. Mammotrophic
      effects of relaxin in rodents have now been extended to pigs, with evidence that
      relaxin is necessary for normal mammary parenchymal development in late
      pregnancy. In most instances the mechanisms responsible for, and the
      physiological significance of, these diverse biological effects remain to be
      elucidated.

PMID- 8145202
TI  - Studies of uterine secretions and products of primary cultures of endometrial
      cells in pigs.
AB  - The uterus plays a central role in the reproductive biology of mammals.
      Adaptation of the uterus from an oviparous to a viviparous nature required
      changes that involved production of a uterine environment that could support the
      development of the embryo and fetus. Production of a suitable environment
      includes the synthesis and secretion of products by the uterine endometrium.
      However, the uterine endometrium is not a single homogeneous unit, but rather
      consists of several cell populations. Recent accomplishments in cell culture
      techniques provide a means for examining the contributions and secretory control
      of different endometrial cell populations. Furthermore, it is possible to
      recombine specific cell types to study their interaction. It is clear that the
      luminal epithelium, glandular epithelium and endometrial stroma produce different
      secretory products. Some secretions (for example uteroferrin) are secreted by
      only one cell type; others (for example prostaglandins, PGs) are secreted by all
      types of cell. There is much to be learned about the functions and regulations of
      endometrial secretions and there are important aspects of the role of the
      endometrium in pregnancy that present concepts do not address. For example, there
      is no explanation for the required synchrony between the embryo and uterus before
      day 10 and the implications of control of the uterine environment by progesterone
      from day 4 to day 10 are not understood. Almost all of the uterine secretory
      proteins are produced after day 10. In this review, we consider the protein and
      prostaglandin products from the different cell populations of the pig endometrium
      and propose a model to explain the integration of multiple sources of PGs and
      multiple regulators of PG secretion. Our purpose is to facilitate a more complete
      understanding of the individual uterine cell populations and a better
      understanding of how these cell types interact to function as a complete unit.

PMID- 8145203
TI  - Embryo-uterine interactions in pigs during week 2 of pregnancy.
AB  - The second week of pregnancy is a particularly critical period for embryonic
      survival in pigs. Within that time, conceptus oestrogen synthesis is initiated,
      spacing and final placement of conceptuses is completed, and the signal for
      extending the functional lifespan of the corpora lutea is received by the mother.
      There is also a marked increase in blood flow to the uterus and the uterine
      endometrium produces and secretes nutrient histotrophe. Conceptus-derived
      oestrogen has been implicated in many of these events. It is also during this
      period that the trophoblast elongates dramatically and the inner cell mass starts
      to differentiate into the embryo proper. Here, we critically review the evidence
      that oestrogen is the sole factor initiating long-term corpus luteum maintenance
      in pigs. We also review the functions and general properties of the major
      secretory proteins in histotrophe and the role of oestrogen in controlling their
      expression. It is now generally accepted that asynchrony within a litter
      underlies much of the losses of conceptuses that are otherwise genetically
      normal, but which are lagging in their development; however, the underlying
      mechanisms remain unclear. Here we hypothesize that oestrogenic compounds derived
      from more advanced conceptuses or provided prematurely, either by injection or in
      the diet, trigger a massive increase in uterine expression and secretion of
      retinol-binding protein laden with retinol. We propose that less developed,
      smaller conceptuses are least able to contend with the sudden exposure to this
      potential teratogen at a time when they are particularly susceptible to imbalance
      in retinol supply. Hence, even though their growth proceeds for a few days, their
      developmental potential is irrevocably compromised.

PMID- 8145204
TI  - Seasonal effects on fertility in gilts and sows.
AB  - The ancestral wild pig is a short day length seasonal breeder. The domestic pig
      appears to have retained some of this seasonality as evidenced by a reduction in
      fertility during the summer-autumn period. The most important aspect of this
      seasonality is a reduction in the number of mated sows that farrow. Many of these
      sows conceive and embryos develop normally for 20-25 days before pregnancy is
      terminated and the sow returns to oestrus (25-35 days after mating). In other
      species, transduction of photoperiodic information is achieved by release of
      melatonin during the dark period. In the pig, the pattern of melatonin secretion
      and the subsequent hypothalamo-pituitary-gonadal responses appear to be more
      complex. A relatively high light intensity is required for pigs to generate a
      distinct diurnal melatonin rhythm and they appear unable to respond appropriately
      to abrupt changes in photoperiod. Pigs on restricted feeding and maintained under
      long photoperiods (but not under short photoperiods) have higher concentrations
      of melatonin than do similarly maintained pigs fed ad libitum. Continuous release
      melatonin implants have a deleterious effect on farrowing rate, suggesting that
      the abnormally high melatonin concentrations observed in sows in summer-autumn
      play a role in the pathogenesis of seasonal infertility. Ad libitum feeding of
      sows during the first few weeks of pregnancy may prevent the increase in
      melatonin concentrations and so remove the seasonal influence on fertility. The
      pituitary response to different photoperiods is also somewhat confusing. Although
      there is some evidence of increased sensitivity to the negative feedback of
      ovarian steroids in the prepubertal gilts and weaned sows during summer-autumn,
      LH concentrations are increased in early pregnant sows. It is proposed that the
      failure of sows to maintain pregnancy in summer-autumn results from disruption of
      maternal recognition of pregnancy causing regression of the corpora lutea, loss
      of pregnancy and return of the sow to oestrus.

PMID- 8145205
TI  - Optimizing semen production for artificial insemination in swine.
AB  - Efficient production of high quality semen is of major importance to artificial
      insemination (AI) organizations. The semen produced should be free of contagious
      organisms, be of high quality, have good storage properties, fertilizing capacity
      and be of high genetic value. The best approach to prevent the spreading of
      microorganisms via semen in the process of AI is to collect semen from boars free
      from specific diseases, for example pseudorabies virus or leptospirosis.
      Antibiotics are added to the semen to suppress proliferation of microorganisms or
      even reduce their number. Sperm production is influenced by many factors such as
      season, collection frequency, breed and age. The average number of sperm cells
      produced per boar per week can vary more than 30% within one AI station,
      depending on the breed. Boar selection and boar management markedly influence the
      efficiency of sperm production. Sperm quality should be evaluated by fertility
      results obtained at breeding farms related to both farrowing rate and litter size
      to ensure a good quality monitoring system. A quality control system should be
      established to provide maximum reliability to customers.

PMID- 8145206
TI  - Optimizing management of natural and artificial matings in swine.
AB  - A successful mating involves the coordination of many physiological events
      including insemination, gamete transport and ovulation. As more basic information
      about these processes becomes available, it is apparent that there are
      opportunities for manipulating these physiological events and enhancing the
      reproductive success of natural and artificial matings. The primary intent of
      this review is to examine the effectiveness of several of these strategies, as
      determined by their influence on farrowing rate and litter size. It is evident
      that the timing, duration and pattern of ovulation in pigs are extremely
      variable. Thus, increasing the frequency and changing the timing of matings
      during oestrus has received renewed interest. In general, if a female exhibits
      oestrus for more than 1 day, then increasing the frequency of matings has a
      greater influence on reproductive performance than does altering the timing of
      matings. In addition, litter size is more responsive to increased mating
      frequencies than is farrowing rate. Increasing the number of matings per oestrus
      via the use of combinations of natural service and artificial insemination,
      compared with the use of either alone, appears to enhance reproductive
      performance. It has been well documented that several aspects of the mating
      process itself can advance the onset of ovulation and enhance sperm transport and
      storage in the female reproductive tract. As a result, the use of these stimuli
      in conjunction with natural and artificial matings provide opportunities for
      enhancing fecundity. Pre- and post-breeding treatments with vasectomized boars,
      nonviable semen, oestrogens and seminal plasma have all been reported to increase
      farrowing rate and litter size. With artificial insemination, additions of
      prostaglandins, oxytocin, oestrogens and leucocytes to semen have been reported
      to enhance reproductive performance, albeit with varying degrees of success.
      Personnel and boar needs are important components in optimizing breeding
      management. Estimates of these needs for artificial and natural matings are
      discussed.

PMID- 8145207
TI  - Effects of nutrition on pregnant and lactating sows.
AB  - It has been suggested that the long-term reproduction of the sow is best served
      by minimizing weight and fat loss in lactation. Such a strategy would require
      only a minimal restoration of weight in the following pregnancy, which would be
      beneficial, since the greater feed intake and weight gain in pregnancy, the
      greater the weight loss in lactation. Feeding ad libitum should be practised
      during lactation while gestation feed intake must be held low. A relationship
      between feed intake and embryo survival has been demonstrated in several studies,
      but the data are sometimes difficult to interpret. High energy feeding during the
      premating period and during early pregnancy, however, are often associated with
      increased embryo mortality. A short-term starvation in lactation decreased
      prolactin to post-weaning concentrations, and insulin and glucose to very low
      concentrations. Prolactin increased very rapidly after refeeding indicating that
      a neural mechanism might be involved. The increasing levels of cholecystokinin
      after refeeding and the neural reflex triggered might be related to this increase
      in prolactin. No changes in LH release were observed during the periods of
      starvation or refeeding. The catabolic rate during the first week of lactation is
      higher in sows with higher backfat thickness than in late gestation. As lactation
      progresses a more balanced metabolism is achieved regardless of backfat thickness
      before parturition. High-weight-loss primiparous sows need a longer recovery
      period from their negative energy balance during lactation than do low-weight
      loss primiparous sows or multiparous sows. Several investigations have
      demonstrated that sows losing excessive amounts of body weight have extended
      weaning to oestrous intervals and an increase in anoestrus. Sows with low body
      weight loss during lactation have higher plasma insulin and lower cortisol around
      weaning than do sows with high body-weight loss. What remains undefined is the
      degree of weight or condition loss below which an extension in the remating
      interval will occur and the level of dietary energy intake required to prevent
      this extension.

PMID- 8145208
TI  - Genetic basis of prolificacy in Meishan pigs.
AB  - Research in France and in the UK confirms the prolificacy of the Chinese Meishan
      breed to be about three to four piglets greater than that of control Large White
      females. Crossbreeding studies clearly indicate that this breed difference is due
      to genes acting in the dam and not in the litter itself. There is high heterosis
      for litter size in F1 Meishan x Large White crossbred females, such that their
      litter size is similar to or greater than that of purebred Meishan females. There
      is some discrepancy between studies about whether the Meishan female has a higher
      ovulation rate than does the Large White breed and this can be attributed in
      large part to the different basis upon which breed comparisons have been made.
      Nevertheless, there may be real genetic differences between Meishan pigs exported
      to different countries. In young gilts at comparable numbers of oestrous cycles
      after puberty, the ovulation rate is similar in Meishan and Large White gilts,
      but in older gilts, and particularly in multiparous sows, Meishan pigs have a
      higher ovulation rate in British studies. Once comparisons of prenatal survival
      between breeds have been adjusted for any breed difference in ovulation rate, the
      main cause of prolificacy in Meishan pigs can be seen to be an enhanced level of
      prenatal survival. Crossbreeding studies show that this is controlled by the
      maternal genotype and not that of the embryos. The advantage in prenatal survival
      to the Meishan pig is clearly present in the post-attachment period (after day 20
      of gestation), but may also be present earlier in gestation. Results from a study
      presented here suggest that Meishan sows have a higher uterine capacity than do
      Large White sows and this allows them to maintain their higher number of attached
      embryos through gestation. F1 Meishan x Large White crossbred females achieve
      their high litter size via a different route than do purebred Meishan females.
      These animals have a lower ovulation rate and fewer attached embryos than do
      purebred Meishan sows, but a very low level of fetal loss allows them to produce
      litters of similar size. The low level of fetal loss in F1 females appears to be
      due to the higher uterine capacity of F1 females compared with purebred Meishan
      sows.

PMID- 8145209
TI  - Endocrine and follicular studies in Meishan pigs.
AB  - The enhanced early embryonic survival in Chinese Meishan compared with Large
      White gilts may be due, in part, to differences in ovarian and endocrine
      function, particularly during the periovulatory period. The overall patterns of
      oestradiol, LH and FSH secretion were not different between Meishan and Large
      White hybrid controls during this period, although circulating inhibin
      concentrations were higher in Meishan gilts. Thus, there appeared to be a
      decreased sensitivity to inhibin feedback on FSH secretion in Meishan gilts.
      Behavioural oestrus was exhibited earlier relative to the LH surge in Meishan
      gilts than in Large-White hybrid gilts, but the time interval from the oestradiol
      peak until the LH surge was similar in both breeds. This finding suggests that
      Meishan gilts are more sensitive in terms of initiating a behavioural response,
      but not in terms of positive feedback. Although preovulatory follicular
      characteristics were as variable in Meishan as in Large-White hybrid gilts,
      follicles from Meishan gilts were smaller, but contained a higher concentration
      of oestradiol in the follicular fluid. This was probably due to increased
      aromatase activity in both granulosa and theca cells of Meishan follicles. The
      enhanced maturation of the intrafollicular environment in Meishan gilts was
      reflected in the oocyte population which was at a more advanced stage of
      development in the period preceding ovulation. In addition to decreasing the time
      between onset of oestrus and ovulation, advancing the LH surge to coincide with
      onset of oestrus (via hCG administration) decreased embryo survival at day 30 of
      gestation. It is concluded that both endocrine and follicular mechanisms have a
      role in ensuring the prolificacy in the Meishan breed.

PMID- 8145210
TI  - Early embryonic development in prolific Meishan pigs.
AB  - Prenatal mortality in European pigs is estimated at 30-40%, the majority of which
      occurs between days 12 and 18 after mating. Chinese Meishan pigs are prolific,
      averaging three to five more pigs per litter than do European breeds. Early
      reports into the fecundity of Meishan females suggested that their prolificacy
      resulted from lower embryonic mortality when compared with European females
      exhibiting the same ovulation rate. The preponderance of evidence suggests that
      there are no differences between Meishan and European breeds in either
      morphological embryo diversity within a litter or embryo mortality before day 12
      after mating. Recent studies from our laboratory suggest that preimplantation
      embryos from Meishan females exhibit markedly reduced growth rates and oestrogen
      secretory activities through day 12 when compared with embryos from Yorkshire
      females. The significantly reduced conceptus sizes of Meishan versus European
      breeds on day 30 of gestation provide additional evidence of the reduced growth
      rate of Meishan embryos. Furthermore, because embryonic oestrogen production is
      known to alter uterine secretion of histotroph, the lower oestrogen production by
      Meishan embryos in the Meishan uterus may result in more gradual alterations in
      the uterine environment that are beneficial for conceptus survival and subsequent
      litter size. Recent studies using cross-transfer of Meishan and Yorkshire embryos
      on day 2 after mating have led to the suggestion that there is a major effect of
      recipient genotype on embryonic growth rate and oestrogen secretion. In these
      studies, both Meishan and Yorkshire embryos transferred to Meishan uteri
      exhibited marked decreases in morphological development and oestrogen content on
      day 12 when compared with embryos transferred to Yorkshire recipients. These data
      suggest the presence of factor(s) in endometrial secretions from Meishan females
      that reduce the growth rate and oestrogen secretory potential of preimplantation
      conceptuses.

PMID- 8145211
TI  - Uterine function in Meishan pigs.
AB  - The Meishan pig provides a biological model with the genetic capacity to express
      a high prolificacy. This prolificacy can be partially attributed to a higher
      ovulation rate and a higher rate of prenatal survival at a given ovulation rate
      throughout gestation than in European breeds. Both early embryonic survival
      (factors inherent to the ovum and uterus, which occur before day 25 of gestation)
      and uterine capacity (factors inherent to uterine limitation, which occur from 30
      days of gestation to parturition) may contribute to prenatal survival.
      Crossbreeding studies show that the prolificacy of Meishan pigs is primarily of
      maternal origin, but not whether the effects occur via the ovum, uterus or
      systemic factors. Although there have been few comparative studies on uterine
      function for prolific pigs, experiments relating to three general areas have been
      reported. During neonatal uterine development, endometrial gland development
      occurs shortly after birth in Meishan and European breeds. Tissue culture for 24
      h showed that secretion of at least three uterine proteins (one identified as
      retinol-binding protein) increased in clear temporal association with development
      of the endometrial gland. The secretion of two additional proteins appears to
      change in a breed-specific manner. Although regulatory roles for uterine proteins
      remain to be defined, biochemical events associated with neonatal endometrial
      gland development may affect subsequent adult uterine function. During the time
      of maternal recognition of pregnancy or early gestation, reports suggest that
      uterine secretions are enhanced in Meishan pigs, which may partially explain
      their increased prolificacy. However, other studies show smaller embryo and
      placental weights at day 30 of gestation, suggesting that prolificacy of Meishan
      females is related to a maternal ability to control embryo/fetal and placental
      growth. During the later fetal period (uterine capacity) in European pigs,
      endometrial response to a crowded uterine environment is minimal, but the
      conceptus responds to a crowded uterine environment by altering placental
      function; similar experiments using Meishan pigs are in progress. Once the
      regulatory determinants of uterine function are understood, improvements can
      possibly be made in the reproductive efficiency of all swine.

PMID- 8145212
TI  - Follicle-oocyte-sperm interactions in vivo and in vitro in pigs.
AB  - In vitro culture has provided new information on the mechanisms involved in
      fertilization where two completely different cells fuse together. At the same
      time, results obtained in vitro have led to new questions. Does the follicle
      influence the final maturation process of the oocyte and does the oviduct
      regulate the normal behaviour of spermatozoa? Recent studies indicate a critical
      influence of both the follicular compartment and the oviduct on the normal
      fertilization process. Oocytes matured in vivo are more competent to induce
      pronuclear formation, but are still susceptible to polyspermy. Oocytes matured in
      vitro can develop fully after fertilization, but require the presence of
      follicular factors during culture to enhance their developmental competence.
      Fresh or frozen spermatozoa can penetrate oocytes in vitro, but their
      conditioning by differential centrifugation or oviductal cells influences the
      rate of polyspermy. The understanding of these influences is a prerequisite to
      enhancing in vitro production of pig embryos.

PMID- 8145213
TI  - Cytoplasmic inheritance and its effects on development and performance.
AB  - In contrast to nuclear inheritance, cytoplasmic inheritance in mammals is derived
      mostly, if not exclusively, from the maternal line. Mitochondria, and their DNA
      molecules (mtDNA), are the genetic units of this method of inheritance. Mammalian
      mtDNA codes for 13 enzymes used in the mitochondrial energy-generating pathway,
      oxidative phosphorylation, 22 tRNAs and two rRNAs. Although all transcripts of
      mtDNA and their translational products remain in the mitochondria, most proteins
      used in mitochondria are from nuclear DNA and are imported after synthesis on
      cytoplasmic ribosomes. Spermatozoa introduce a small number of mitochondria into
      the cytoplasm of the egg at fertilization, which appear to be digested soon after
      penetration. Although the paternal contribution of mtDNA to the offspring is not
      believed to occur in mammals, some interspecific crosses have suggested that it
      does occur. Experiments with animals derived from reconstituted embryos, using
      nuclear or cytoplasmic transplantations, suggest that nuclear-mitochondrial
      interactions are important but not essential in the survival and replication of
      exogenous mitochondria introduced into the egg. As the levels of heteroplasmy
      varied in several tissues of animals derived from reconstituted embryos, it is
      suggested that differential partitioning of mitochondria occurs during
      embryogenesis. Mitochondrial morphology changes substantially during oogenesis
      and throughout early cleavage stages. Somatic morphology and normal replication
      patterns are regained at the blastocyst stage. In pig oocytes and embryos,
      mitochondria aggregate and are closely associated with endoplasmic reticulum,
      lipid granules and large vesicles. Although the direct correlation of
      mitochondrial genes with reproductive traits is still unclear, some human
      degenerative diseases and performance traits in cattle can be related directly to
      specific mtDNA polymorphisms. In pigs, reciprocal-cross comparisons have
      indicated greater offspring parent similarity with dam than sire for lean:fat
      ratio. A difference was also observed for oxygen consumption and oxidative
      phosphorylation, but not for anaerobic energy metabolism, in a pig reciprocal
      cross experiment. Information on the transmission of mtDNA and its effects on
      performance will have many implications not only for our understanding of
      mitochondrial genetics but also for the increased productivity of animals. There
      are also potential ramifications to the animal cloning industry.

PMID- 8145214
TI  - Effectiveness of in vitro maturation and in vitro fertilization techniques in
      pigs.
AB  - In vitro maturation and in vitro fertilization techniques in pigs have progressed
      considerably in recent years. Many reports focus on the factors affecting in
      vitro maturation that lead to normal male pronuclear formation or monospermy
      after fertilization in vitro. It is suggested that pig follicular fluid (pFF),
      follicle somatic cells and various hormones are important factors for the
      maintenance of cytoplasmic maturation of oocytes in vitro, but that fetal calf
      serum (FCS), which is generally added to maturation medium, is detrimental. A
      series of experiments clearly indicate that the glutathione (GSH) content of
      matured oocytes increases greatly when maturation medium is supplemented with
      cysteine, a precursor of GSH, and the rates of male pronuclear formation increase
      in parallel with the increasing GSH content. To prevent polyspermy, conditions of
      maturation and of fertilization in vitro are important. Culture of oocytes in
      medium with FCS for the first 24 h and with BSA for the second 24 h decreases the
      incidence of polyspermy, without a significant effect on nuclear maturation.
      However, it has been shown that secretory macromolecules of the oviduct may
      reduce the incidence of polyspermy by interacting with fertilizing spermatozoa
      rather than with oocytes. A reduction of polyspermy by treating spermatozoa with
      pFF is also reported. In addition to the many improvements in the methodology of
      in vitro fertilization using unfrozen spermatozoa in pigs, techniques for
      fertilizing oocytes in vitro with frozen epididymal and ejaculated spermatozoa
      have also recently been developed.

PMID- 8145215
TI  - Culture of pig embryos.
AB  - Pig embryos can be cultured using a number of different strategies including
      complex approaches like culture in vivo in a surrogate oviduct (rabbit, sheep,
      mouse), culture in mouse oviducts in organ culture, and co-culture of embryos
      with cells in addition to simple approaches like culture in defined media or salt
      solutions. Addition of serum to medium has been of particular importance where
      blastocyst development and hatching are required. Pig conceptuses (day 10-15),
      embryonic discs or cell lines derived from conceptuses can be cultured in complex
      media like Eagle's minimal essential medium or Dulbecco's modified Eagle's medium
      with serum, although embryonic discs can be cultured in the absence of serum. In
      contrast, early stage pig embryos (one-cell to blastocyst) are best cultured in
      simpler media such as those used for mouse embryos. The media that have been used
      are all relatively similar in composition. They contain salts and one or more
      energy sources such as glucose, lactate, or pyruvate with BSA as a macromolecular
      component. Early attempts to culture pig embryos were not very successful, but
      some embryos did develop to the blastocyst stage. More recent reports indicate a
      much higher rate of development with relatively little or no change in media
      composition. Some workers have reported improved development in medium lacking
      glucose, which is consistent with findings with laboratory animals such as
      hamsters. Glutamine can serve as the sole exogenous energy source in medium
      lacking glucose, lactate and pyruvate. Addition of taurine and hypotaurine to
      culture medium enhances development of pig embryos in vitro. We suggest, where
      possible, adoption of a standard medium that could be used by different
      laboratories and, perhaps, with different species. Use of one medium for
      different species would simplify experimental protocols, enhance studies of
      comparative embryonic physiology and metabolism, and expedite transfer of
      information obtained in different species.

PMID- 8145216
TI  - Manipulating early pig embryos.
AB  - On the basis of established surgical procedures for embryo recovery and transfer,
      the early pig embryo can be subjected to various manipulations aimed at a long
      term preservation of genetic material, the generation of identical multiplets,
      the early determination of sex or the alteration of the genetic make-up. Most of
      these procedures are still at an experimental stage and despite recent
      considerable progress are far from practical application. Normal piglets have
      been obtained after cryopreservation of pig blastocysts hatched in vitro, whereas
      all attempts to freeze embryos with intact zona pellucida have been unsuccessful.
      Pig embryos at the morula and blastocyst stage can be bisected microsurgically
      and the resulting demi-embryos possess a high developmental potential in vitro,
      whereas their development in vivo is impaired. Pregnancy rates are similar (80%)
      but litter size is reduced compared with intact embryos and twinning rate is
      approximately 2%. Pig blastomeres isolated from embryos up to the 16-cell stage
      can be grown in culture and result in normal blastocysts. Normal piglets have
      been born upon transfer of blastocysts derived from isolated eight-cell
      blastomeres, clearly underlining the totipotency of this developmental stage.
      Upon nuclear transfer the developmental capacity of reconstituted pig embryos is
      low and < 10% develop to morulae or blastocysts in vitro. Pig oocytes can be
      stimulated parthenogenetically and up to 10% grow to blastocysts in the in vitro
      culture. Sex determination can be achieved either by separation of X and Y
      chromosome bearing spermatozoa by flow cytometry or by analysing the expression
      of the HY antigen in pig embryos from the eight-cell to morula stage.
      Microinjection of foreign DNA has been successfully used to alter growth and
      development of transgenic pigs, and to produce foreign proteins in the mammary
      gland or in the bloodstream, indicating that pigs can be used as donors for
      valuable human pharmaceutical proteins. Another promising area of gene transfer
      is the increase of disease resistance in transgenic lines of pigs. Approximately
      30% of pig spermatozoa bind considerable amounts of foreign DNA preferably at the
      post-acrosomal region, suggesting that transgenic animals can be obtained more
      efficiently than with the usual microinjection procedure. To increase gene
      transfer efficiency, considerable research efforts have been made to establish
      embryonic stem (ES) cells, but so far there is no definite proof of totipotency
      of the generated pig ES-like cells through viable chimaeras. In general,
      biotechnological procedures are much less advanced in pigs than in cows.

PMID- 8145217
TI  - Early uterine development in pigs.
AB  - The capacity of pig uterine tissues to recognize and respond to maternal and
      conceptus signals determines whether pregnancy can be established and defines the
      environment in which embryonic and fetal growth occur. Limits of uterine capacity
      may be defined genetically. However, the extent to which functional uterine
      capacity approaches genetic potential may be determined, in part, by the success
      of organizational events associated with growth, morphogenesis and
      cytodifferentiation of uterine tissues. It is important, therefore, that these
      events be identified and evaluated with respect to their potential effect on
      adult uterine function. Histogenesis of the pig uterus begins prenatally, but is
      completed postnatally. Transformation of the uterine wall from histoarchitectural
      infancy to maturity occurs between birth and day 120. Morphogenetic events
      characteristic of the first 60 days of neonatal life proceed normally in gilts
      ovariectomized at birth. These events include appearance and proliferation of
      uterine glands, development of endometrial folds, and growth of the myometrium.
      Endometrial development during this period involves alterations in patterns of
      epithelial and stromal DNA synthesis, coordinated changes in the distribution and
      biosynthesis of extracellular matrix glycosaminoglycans and cell surface
      glycoconjugates, and specific alterations in patterns of uterine protein
      secretion. The ovary-independent, spatially coordinated nature of these events
      suggests that neonatal uterine development is regulated locally via dynamic cell
      cell and cell-extracellular matrix interactions. The extent to which such
      potentially critical interactions must be preserved to ensure developmental
      success remains unknown. However, the normal pattern of ovary-independent
      cellular and molecular events associated with development of the uterine wall was
      disrupted by treating neonatal gilts with oestradiol valerate, and daily
      administration of oestrogen to gilts from birth to day 13 did not affect
      ovulation rate, but did reduce embryonic survival by 22% on day 45 of gestation
      in adults that were exposed to oestrogen neonatally. These observations support
      the idea that some organizational events associated with development of the
      neonatal uterine wall must be allowed to proceed without interruption to ensure
      that adult uterine function is not compromised. Efforts to identify specific
      developmental determinants of uterine capacity may be facilitated by examining
      the consequences of xenobiotically induced interruption of uterine development on
      adult uterine function. Such studies may also contribute to identification of
      uterine factors affecting embryonic survival and fetal growth.

PMID- 8145218
TI  - 3-Alkoxybenzo[b]thiophene-2-carboxamides as inhibitors of neutrophil-endothelial
      cell adhesion.

PMID- 8145219
TI  - High-affinity and potent, water-soluble 5-amino-1,4-benzodiazepine CCKB/gastrin
      receptor antagonists containing a cationic solubilizing group.

PMID- 8145220
TI  - Second-generation benzodiazepine CCK-B antagonists. Development of subnanomolar
      analogs with selectivity and water solubility.

PMID- 8145221
TI  - Pseudopeptide inhibitors of Ras farnesyl-protein transferase.
AB  - Inhibitors of Ras farnesyl-protein transferase are described. These are reduced
      pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that
      signals farnesylation. Deletion of the carbonyl groups between the first two
      residues of the tetrapeptides either preserves or improves activity, depending on
      the peptide sequence. The most potent in vitro enzyme inhibitor described (IC50 =
      5 nM) is Cys [psi CH2NH]Ile[psi CH2NH]Phe-Met (3). To obtain compounds able to
      suppress Ras farnesylation in cell culture, further structural modification to
      include a homoserine lactone prodrug was required. Compound 18 (Cys[psi
      CH2NH]Ile[psi CH2NH]Ile-homoserine lactone) reduced the extent of Ras
      farnesylation by 50% in NIH3T3 fibroblasts in culture at a concentration of 50
      microM. Structure-activity studies also led to 12 (Cys[psi CH2NH]Val-Ile-Leu), a
      potent and selective inhibitor of a related enzyme, the type-I geranylgeranyl
      protein transferase.

PMID- 8145222
TI  - Synthesis and antibacterial activity of new quinolones containing a 7-[3-(1-amino
      1-methylethyl)-1-pyrrolidinyl] moiety. Gram-positive agents with excellent oral
      activity and low side-effect potential.
AB  - A series of the R and S isomers of 7-[3-(1-amino-1-methylethyl)-1-pyrrolidinyl]
      1,4-dihydro-4-oxoquinoline- and 1,8-naphthyridine-3-carboxylic acids was prepared
      to determine the effect on potency of the two methyl groups adjacent to the
      distal nitrogen in the pyrrolidinyl moiety. The antibacterial efficacy of these
      dimethylated derivatives was compared to the relevant 7-[3-(aminomethyl)-1
      pyrrolidinyl] parent compounds and, to a lesser extent, the 7-[3-(1-aminoethyl)-1
      pyrrolidinyl] analogues. The activity of the title and reference compounds was
      assayed in vitro using an array of Gram-negative and Gram-positive organisms and
      in vivo using a mouse infection model. Selected derivatives were then screened
      for potential side effects in a phototoxicity mouse model and an in vitro
      mammalian cell cytotoxicity protocol. The results showed that the R isomer
      displayed a 2-20-fold advantage in activity in vitro and a 2-15-fold advantage in
      vivo over the S isomer. Although equipotent to the 7-[3-(aminomethyl)-1
      pyrrolidinyl] parent compounds in vitro, the R isomers of the 7-[3-(1-amino-1
      methylethyl)-1-pyrrolidinyl] analogues showed a dramatic increase in in vivo
      potency, especially via the oral route of administration. These same R isomers
      also appeared to possess a reduced risk of phototoxicity and cytotoxicity. This
      combination of superior in vivo performance with a low degree of phototoxicity
      and mammalian cell cytotoxicity recommends these agents for further study. Of
      these agents, naphthyridine 16-R represents the optimal blend of potency and
      safety.

PMID- 8145223
TI  - Phosphonate analogs of carbocyclic nucleotides.
AB  - Cyclopentadiene was converted in six steps to the key intermediate (+/-)-(1
      alpha,2 beta,4 alpha)-4-amino-2-(benzyloxy)cyclopentanol (10), which in turn was
      converted to the carbocyclic nucleoside analogs 14 and 19 by standard procedures
      developed in these laboratories. Compounds 14 and 19 were then further converted
      to the target phosphonates 1b and 2b by modification of literature procedures.
      The phosphonate 1b was 40-fold more cytotoxic to HEp-2 cells than its parent,
      CDG, presumably after conversion to the diphosphoryl phosphonate.

PMID- 8145224
TI  - Synthesis of benzo-fused benzodiazepines employed as probes of the agonist
      pharmacophore of benzodiazepine receptors.
AB  - The synthesis and in vitro evaluation of benzo-fused benzodiazepines 1-6 are
      described. These "molecular yardsticks" were employed to probe the spatial
      dimensions of the lipophilic pocket L2 in the benzodiazepine receptor (BzR) cleft
      and to determine the effect of occupation of L2 with respect to agonist activity.
      Of the new analogs synthesized, the 7,8-benzo-fused benzodiazepine 6 displayed
      moderately high affinity for the BzR (IC50 = 55 nM) and exhibited both
      anticonvulsant (ED50 approximately 15 mg/kg) and muscle relaxant (ED50
      approximately 15 mg/kg) activity. As expected, 2 and 4 interacted with the
      repulsive regions of interaction, S1 and S2, and exhibited low affinities for
      BzR. The rigid nature of these molecular yardsticks (especially 6, Figure 7) has
      been employed to probe the depth of L2. Moreover, in the case of 6 full
      occupation of L2 has resulted in an increase in the muscle relaxant effect at the
      expense of the anticonvulsant/anxiolytic effect.

PMID- 8145225
TI  - Antagonist, partial agonist, and full agonist imidazo[1,5-a]quinoxaline amides
      and carbamates acting through the GABAA/benzodiazepine receptor.
AB  - (4RS)-1-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-12,12a-dihyd roimidazo[1,5-
      a]pyrrolo[2,1-c]quinoxalin-10(11H)-one (1a), 5-benzoyl-3-(5-cyclopropyl-1,2,4
      oxadiazol-3-yl)-4,5- dihydroimidazo[1,5-a]quinoxaline (13b), and tert-butyl (4S)
      12,12a-dihydroimidazo[1,5-a]pyrrolo[2,1- c]quinoxaline-1-carboxylate (1e), as
      well as other imidazo[1,5-a]quinoxaline amides and carbamates, represent a new
      series of compounds which bind with high affinity to the GABAA/benzodiazepine
      receptor. These compounds exhibit a wide range of intrinsic efficacies as
      measured by [35S]TBPS binding ratios. The synthesis of 1a begins with the
      addition of DL-glutamic acid to 1-fluoro-2-nitrobenzene, followed by reduction of
      the nitro group and subsequent ring closure to form 3-(carbethoxymethyl)-1,2,3,4
      tetrahydroquinoxalin-2-one, followed by a second ring closure to afford (4RS)-1,5
      dioxo-1,2,3,4,5,6-hexahydropyrrolo[1,2-a]quinoxali ne as the key intermediate.
      Appendage of a substituted imidazo ring via the anion of 5-cyclopropyl-1,2,4
      oxadiazol-3-yl gives 1a. The (-)- and (+)-isomers of 1a were prepared from 1
      fluoro-2-nitrobenzene and L- and D-glutamic acid, respectively. 1a and its
      enantiomers demonstrated affinity for the [3H]flunitrazepam binding site with
      Ki's of 0.87, 0.62, and 0.65 nM, respectively.

PMID- 8145226
TI  - Conformationally constrained peptides and semipeptides derived from RGD as potent
      inhibitors of the platelet fibrinogen receptor and platelet aggregation.
AB  - Structure-activity studies have been pursued on cyclo-S,S-[Ac-Cys-(N alpha-Me)Arg
      Gly-Asp-Pen]-NH2, 2 (SK&F 106760), a potent inhibitor of platelet aggregation, in
      an effort to improve potency and affinity for the GPIIb/IIIa receptor.
      Modifications on the N- and C-termini of 2 produced a series of peptides which
      indicate that the C-terminal carboxylate group may be a secondary receptor
      binding element. Further modification by replacing the disulfide tether N alpha
      acetylcysteine/penicillamineamide with the novel, inexpensive, achiral,
      constrained, and more lipophilic tether 2-mercaptobenzoyl/2-mercaptoaniline
      (Mba/Man) afforded the semipeptide cyclo-S,S-[Mba-(N alpha-Me)Arg-Gly-Asp-Man],
      18 (SK&F 107260), which exhibited significant enhancement in both affinity and
      potency. To further investigate the effect of the phenyl ring at the C-terminus,
      peptides bearing the novel (2R,3S)- and (2R,3R)-beta-phenylcysteines were
      synthesized, which culminated in the cyclo-S,S-[Ac-Cys-(N alpha-Me)Arg-Gly-Asp
      (2R,3S)-beta-phenylCys]-OH peptide, 22, which displayed substantial affinity and
      potency. We describe, herein, the development of both 18 and 22 and the
      additional structural modifications within the constrained cyclic disulfide ring
      to probe the stereochemical and steric requirements for receptor interaction.

PMID- 8145227
TI  - Comparative molecular field analysis of the antitumor activity of 9H-thioxanthen
      9-one derivatives against pancreatic ductal carcinoma 03.
AB  - The present study establishes correlations of in vivo growth inhibition of a
      solid tumor, pancreatic ductal adenocarcinoma (Panc03), of mice with the steric
      and electrostatic fields and the hydrophobic parameter log P of a series (32) of
      1-[[2-(dialkylamino)alkyl]amino]- 9H-thioxanthen-9-ones by the 3D-QSAR method
      comparative molecular field analysis (CoMFA). The template molecular model was
      hycanthone methanesulfonate (19), the structure of which had been established
      previously by X-ray crystallography. The hycanthone base is protonated at the
      terminal nitrogen N(2), and an intramolecular hydrogen bond is present between
      the proximal nitrogen N(1) and carbonyl oxygen O(1) atoms. Crystallographic data
      also indicate a planar arrangement of bonds around N(1). However, the molecular
      geometry of 19, optimized by semiempirical molecular orbital methods (PM3, MNDO,
      AM1), showed the expected trigonal-pyramidal configuration for N(1). A comparison
      of MO and ab initio methods applied to a model compound, 1-amino-9H-thioxanthen-9
      one, led to the selection of PM3 as the method for full geometry optimization of
      first the cationic and then the neutral forms of 1-32, whereas AM1 provided
      atomic charges for these same structures save those incorporating a sulfonamide
      moiety (5, 7, 20, 25, 26, 29, 31, and 32). Acceptable values for the latter were
      obtained from ab initio calculations. Structures were aligned by minimizing root
      mean-square (rms) differences in the fitting of structures to 19 using the FIT
      option of SYBYL. An alternative strategy of alignment, steric and electrostatic
      alignment (SEAL), was invoked to provide a comparison of statistical data
      generated with the rms alignment. The rms-fit alignment of structures produced
      slightly better cross-validated and conventional r2 values than those generated
      with the SEAL method. In addition, the rms-fit data indicate that a shift in the
      lattice of one-half of its spacing has a much smaller effect on the CoMFA data
      for a lattice of 1 A than one of 2 A. Inclusion of log P in a CoMFA of the
      neutral structures effected a small (ca. 8-10%) but significant improvement in
      cross-validated r2 values. The relative contributions of the hydrophobic effects
      and the steric and electrostatic fields to the conventional r2 values were 16%,
      42%, and 42%, respectively. By contrast, incorporation of frontier molecular
      orbital (HOMO and LUMO) energies or their gaps in the PLS analyses failed to
      enhance correlation coefficients derived for either the charged or uncharged
      compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145228
TI  - Molecular modeling studies of aldose reductase inhibitors.
AB  - Molecular modeling studies using the AM1 quantum chemical method and a torsional
      fitting method have been conducted on a series of aldose reductase inhibitors
      (ARIs) possessing an ionizable group and/or functional group susceptible to
      nucleophilic attack with the aim of defining the spatial position of ARI
      pharmacophores. AM1 quantum chemical calculations were conducted on ARIs
      possessing only an ionizable group to obtain their optimized geometries. These
      optimized structures were then superimposed on the model compound spirofluorene
      9,5'-imidazolidine-2',4'-dione (17). This superposition study suggests that a
      negative charge center residing in the vicinity of the 2'-oxygen of the
      imidazolidine-2',4'-dione ring participates in the binding interactions. In
      addition, the optimized geometries of ARIs possessing both an ionizable group and
      an electronegative functional group were superimposed on spirofluorene-9,5'
      imidazolidine-2',4'-dione (17). The latter results also suggest the presence of a
      region where nucleophilic substitution can occur.

PMID- 8145229
TI  - HIV-inhibitory natural products. 11. Comparative studies of sulfated sterols from
      marine invertebrates.
AB  - A total of 22 sulfated sterols isolated from marine sponges, ophiuroids (brittle
      stars), and asteroids (sea stars) were comparatively evaluated for their
      antiviral activity against HIV-1 and HIV-2. In general, sterols with sulfate
      groups at position 2, 3, or 6 were the most active, with EC50 values of 3-13
      microM against HIV-1 (RF) and 2-8 microM against HIV-2 (CBL20). Those compounds
      which were sulfated on the sterol D ring were completely inactive against both
      HIV-1 and HIV-2. Overall, sulfated sterols active against HIV-1 were also active
      against HIV-2.

PMID- 8145230
TI  - Synthesis and biological evaluation of 2',3'-dideoxy-L-pyrimidine nucleosides as
      potential antiviral agents against human immunodeficiency virus (HIV) and
      hepatitis B virus (HBV).
AB  - Various 2',3'-dideoxy-L-cytidine,2',3'-dideoxy-L-uridine, and 3'-deoxy-L
      thymidine analogues have been synthesized and evaluated in vitro as potential
      anti-HIV and anti-HBV agents. Coupling of 1-O-acetyl-5-O-(tert
      butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (1) with silylated derivatives of
      5-fluorocytosine, cytosine, 5-fluorouracil, uracil, and thymine in the presence
      of ethylaluminum dichloride gave the corresponding nucleosides 2, 3, 4, 5, 10,
      11, 12, 16, 17, and 18 as a mixture of alpha- and beta-anomers, which were then
      deblocked to yield the corresponding 2',3'-dideoxy-L-5-fluorocytidine
      derivatives, 6 and 7, 2',3'-dideoxy-L-cytidine derivatives, 8 and 9, 2',3'
      dideoxy-beta-L-fluorouridine (13), 2',3'-dideoxy-beta-L-uridine (14), and 3'
      deoxy-L-thymidine derivatives, 15 and 19. Among these 2',3'-dideoxy-L-nucleoside
      analogues, 2',3'-dideoxy-beta-L-5-fluorocytidine (6, beta-L-FddC) was found to be
      the most active against HIV-1, which is approximately 3 and 4 times more active
      against HIV-1 in vitro than 2',3'-dideoxy-beta-D-cytidine (ddC) and 2',3'-dideoxy
      beta-D-5-fluorocytidine (beta-D-FddC) with ED50 values of 0.5, 1.5, and 2 microM,
      respectively. The dose-limiting toxicity of ddC is severe neuropathy which may be
      caused by the inhibition of the synthesis of mitochondrial DNA. ddC has an IC50
      value of 0.022 microM against host mitochondrial DNA synthesis. Conversely, the
      IC50 values for beta-L-FddC and beta-L-ddC are > 100 microM; therefore,
      neuropathy may not present itself to be a problem with beta-L-FddC and beta-L-ddC
      as chemotherapeutic agents. In addition, beta-L-FddC and 2',3'-dideoxy-beta-L
      cytidine (8, beta-L-ddC) demonstrated equally potent activity against HBV in
      vitro by having the same ED50 value of 0.01 microM. Both beta-L-FddC and beta-L
      ddC, which have an "unnatural" L-configuration in the sugar moiety, are
      approximately 1000 and 280 times more potent, respectively, against HBV than the
      D-configuration beta-D-FddC and ddC which have an ED50 values of 10 and 2.8
      microM. In view of the potent antiviral activity of beta-L-FddC against both HIV
      1 and HBV and potent antiviral activity of beta-L-ddC against HBV in vitro, their
      low cytotoxicity, and especially the negligible inhibitory effect on host
      mitochondrial DNA synthesis, beta-L-FddC and beta-L-ddC merit further development
      as potential anti-HIV and anti-HBV agents.

PMID- 8145231
TI  - Inhibitors of acyl-CoA:cholesterol acyltransferase. 1. Synthesis and
      hypocholesterolemic activity of dibenz[b,e]oxepin-11-carboxanilides.
AB  - A series of N-phenyl-6,11-dihydrodibenz[b,e]oxepin-11-carboxamides and related
      derivatives were prepared on the basis of structures of the reported inhibitors
      of acyl-CoA:cholesterol acyltransferase (ACAT). These compounds were tested for
      their ability to inhibit ACAT (liver microsomes from cholesterol-fed rabbits) in
      vitro and to decrease serum total cholesterol in cholesterol-fed golden hamsters
      in vivo. The structure-activity relationships in vitro were as follows.
      Substitution at positions 2 and 6 in the anilide resulted in potent inhibitory
      activity, and the potency increased with increasing size of the substituents,
      with maximum potency being obtained with a 2,6-diisopropyl substitution. The
      position of the substituent on the dibenz[b,e]oxepin ring system influenced the
      activity, and substitution at position 2 was critical for potent activity. The
      electronic effect of the substituent at position 2 does not influence activity,
      but bulkiness seems to be a significant factor. The lipophilicity of the
      compounds also plays an important role in determining ACAT inhibitory activity.
      Among the compounds tested, 2-bromo-N-(2,6-diisopropylphenyl)-6,11-dihydrodibenz
      [b,e]++ +oxepin-11- carboxamide (33, KF17828) showed significant in vitro
      activity (rabbit liver microsomes IC50 = 23 nM) and the most potent in vivo
      activity (complete reduction in elevated serum total cholesterol levels at a dose
      of 10 mg/kg in hamsters).

PMID- 8145232
TI  - [D-TRP32]neuropeptide Y: a competitive antagonist of NPY in rat hypothalamus.
AB  - Neuropeptide Y (NPY) is a potent orexigenic peptide. Structure-activity studies
      have revealed that nearly the entire sequence of NPY is required to elicit
      feeding responses. Therefore, in order to develop antagonistic peptides for NPY
      induced feeding, we synthesized full-length analogs of NPY, substituting D-Trp in
      the C-terminal receptor binding region, and screened their activity in rat
      hypothalamus. Although [D-Trp36]NPY and [D-Trp34]NPY inhibited isoproterenol
      stimulated hypothalamic membrane adenylate cyclase activity, [D-Trp32]NPY
      exhibited no intrinsic activity. Furthermore, [D-Trp32]NPY inhibited [125I]NPY
      binding to rat hypothalamic membranes with a potency comparable to that of NPY.
      The presence of 30 and 300 nM concentrations of [D-Trp32]NPY shifted the
      inhibitory dose-response curve of NPY on isoproterenol-stimulated hypothalamic
      membrane adenylate cyclase activity parallel to the right with comparable KB
      values. Moreover, in vivo experiments in rats revealed that [D-Trp32]NPY (10
      micrograms) significantly attenuated the 1-h feeding response induced by NPY (1
      microgram). Several other substitutions at position 32 including 2-D-Nal resulted
      in agonist activity, suggesting that there are strict structural requirements to
      induce the antagonistic property in NPY. These findings confirm that [D-Trp32]NPY
      is a competitive antagonist of NPY in both in vitro and in vivo systems. Analogs
      based on [D-Trp32]NPY may have potential clinical application, since NPY has been
      implicated in the pathophysiology of a number of feeding disorders including
      obesity, anorexia, and bulimia.

PMID- 8145234
TI  - 6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,10-diones. A novel class of
      chromophore-modified antitumor anthracene-9,10-diones: synthesis and antitumor
      evaluations.
AB  - Synthetic procedures have been developed which lead to the 2-aza congeners 3 and
      several related N-oxides 4. The analogues 3 exhibited a wide range of in vitro
      cytotoxicity against L1210 leukemia, the human colon adenocarcinoma cell line
      LoVo, and the doxorubicin resistant LoVo/DX cell line. Selected analogues of 3
      showed significant P388 antileukemic activity in mice with 3c exhibiting high
      activity. This activity was also retained in the related N-oxide 4a. These
      heterocyclic bioisosteric models are representative of the first anthracene-9,10
      diones which display antileukemic activity comparable to mitoxantrone.

PMID- 8145233
TI  - Enhanced brain delivery of an anti-HIV nucleoside 2'-F-ara-ddI by xanthine
      oxidase mediated biotransformation.
AB  - In order to enhance the brain delivery of 2'-F-ara-ddI,2'-F-ara-ddP 6 was
      synthesized and its in vitro and in vivo bioconversion reaction studied. For the
      study, a new efficient synthetic method for 2'-F-ara-ddP 6 was developed from 5
      benzoyl-1,2-O-isopropylidene-3-deoxyribose 1. For in vitro study 2'-F-ara-ddP was
      incubated in pH 2, mouse liver homogenate, and mouse serum at 37 degrees C. No
      degradation was observed in pH 2 and serum, while in liver homogenate 2'-F-ara
      ddP was almost completely converted to 2'-F-ara-ddI within 20 min (t1/2 = 3.54
      min). In order to determine the role of xanthine oxidase in the conversion of 2'
      F-ara-ddP to 2'-F-ara-ddI, in vitro studies were conducted in phosphate buffer
      (pH 7.4) in the presence or absence of allopurinol, in which the half-lives of 2'
      F-ara-ddP were 7.4 and 3.4 h, respectively, indicating the conversions were
      catalyzed by the xanthine oxidase. A similar experiment with aldehyde oxidase
      isolated from the human liver did not affect the biotransformation. The
      biotransformation was also detected in the brain homogenate, although the rate of
      conversion was low and incomplete. In order to assess the bioconversion in vivo,
      pharmacokinetic studies of 2'-F-ara-ddP and 2'-F-ara-ddI were conducted in mice.
      The maximum serum concentrations of 2'-F-ara-ddI administered itself and as 2'-F
      ara-ddP reached 48.1 +/- 10.00 and 89.3 +/- 26.0 microM and were observed in 1
      and 0.25 h, respectively. The data indicate that 2'-F-ara-ddI is absorbed at a
      slower rate than that of 2'-F-raa-ddP. The bioavailability of the prodrug after
      oral administration was 60.7%. The concentration of 2'-F-ara-ddI following oral
      administration of 2'-ara-ddI was close to the detection limits while 2'-F-ara-ddI
      was detected at significantly higher concentrations in the brain after oral
      administration of 2'-F-ara-ddP. From this study, we have administered the
      enhanced brain delivery of anti-HIV nucleoside utilizing an in vivo
      biotransformation system.

PMID- 8145235
TI  - Benzo[f]quinazoline inhibitors of thymidylate synthase: methyleneamino-linked
      aroylglutamate derivatives.
AB  - Syntheses of several new inhibitors of thymidylate synthase (TS) structurally
      related to folic acid are described in which the pterin portion of the folate
      molecule is replaced by a benzo[f]quinazoline moiety, but which retain the
      natural methyleneamino link to the benzoylglutamate side chain. The effect on
      enzyme activity and cytotoxicity of various changes in the structure of the (p
      aminobenzoyl)glutamate side chain are reported. Replacement of the benzamide
      portion of the (p-aminobenzoyl)glutamate moiety with 2-fluorobenzamido, 2
      isoindolinyl, 1,2-benzisothiazol-2-yl, and 2-thenamido moieties varied in effect
      from a 9-fold diminution of TS activity to a 5-fold enhancement, while cytotoxic
      potency on SW-480 and MCF-7 tumor lines showed increases ranging from 3.6- to 450
      fold. The detrimental effect on enzyme activity and cytotoxicity of alkyl
      substitution on the PABA nitrogen is confirmed for these compounds, in contrast
      with several series of previously reported quinazoline antifolates (2).
      Substitution of a C3-methyl substituent for 3-amino had little effect on TS
      activity but was beneficial in terms of solubility and cytotoxicity. The
      excellent combination of TS inhibitory activity, FPGS substrate activity, and
      affinity for the reduced folate transport system in the most potent of these
      derivatives, 3e, resulted in IC50 values of 0.2-0.8 nM against these tumor lines.

PMID- 8145236
TI  - Structure-activity relationships in a series of 5-[(2,5
      dihydroxybenzyl)amino]salicylate inhibitors of EGF-receptor-associated tyrosine
      kinase: importance of additional hydrophobic aromatic interactions.
AB  - Potent inhibitors of EGF-dependent protein tyrosine kinase (PTK) activity were
      synthesized in a series of 5-[(2,5-dihydroxybenzyl)amino]salicylates. Several of
      these compounds inhibited EGF-dependent DNA synthesis in ER 22 cells with IC50 <
      1 microM. In this series of PTK inhibitors, the role of the salicylate moiety as
      a potential divalent ion chelator was tested and found to be nonessential in all
      cases. The length and ramification of the substituting carboxyl group were
      investigated to improve cellular bioavailability, and this analysis provided
      compounds with increased inhibitory effect on EGF-induced DNA synthesis.
      Salicylates esterified with long hydrophobic chains were shown to be
      noncompetitive inhibitors of ATP, in contrast to the free acid and methyl
      salicylate. Moreover, all the tested inhibitors were shown to be noncompetitive
      inhibitors of the peptide substrate. Structure-activity relationships allowed us
      to suspect a hydrophobic pocket in the tyrosine kinase domain, preferentially
      interacting with aromatic rings. Finally, the selectivity of the best inhibitors
      was tested against other kinases, and they were found to be selective for
      tyrosine kinase. They were also shown to be good inhibitors of EGF-receptor
      autophosphorylation.

PMID- 8145237
TI  - Preferred orientations in the binding of 4'-hydroxyacetanilide (acetaminophen) to
      cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation
      studies.
AB  - The widely used analgesic/antipyretic agent 4'-hydroxyacetanilide (acetaminophen,
      APAP) is oxidized by cytochromes P450 to a potent cytotoxin, N-acetyl-p
      benzoquinone imine (NAPQI), and a nontoxic catechol, 3',4'-dihydroxyacetanilide
      (3-hydroxyacetaminophen, 3-OH-APAP). There are marked differences in the ratios
      of these two products formed from different isoforms of cytochrome P450. For
      example, the ratio of NAPQI to 3-OH-APAP formed by rat liver CYP1A1 was found to
      be approximately 3:1, whereas the ratio of the same two products formed by rat
      liver CYP2B1 was approximately 1:5. Investigations of the binding of APAP to
      CYP1A1 and CYP2B1 were carried out to assess the possibility that different
      preferred orientations of APAP in the active sites of these isoforms may, in
      part, by responsible for their different product selectivities. Although the
      spectral dissociation constants (Ks congruent to 0.85 mM) and UV-vis binding
      spectra (type I; absorption minimum congruent to 420 nm, absorption maximum
      congruent to 390 nm) were similar for interactions of APAP with the two P450
      isoforms, NMR longitudinal relaxation times (T1) of APAP nuclei were
      significantly different. Two isotopically substituted analogs of APAP, [2,3',5'
      13C3]-4'-hydroxyacetanilide and 4'-hydroxyacet-[15N]-anilide, were synthesized,
      and their binding to purified CYP1A1 and CYP2B1 was examined by NMR spectroscopy.
      Paramagnetic relaxation times (T1p) for each of the labeled nuclei were
      calculated from the T1 values obtained before (ferric) and after (ferrous-CO)
      treatment with Na2S2O4 and CO. The Solomon-Bloembergen equation was then used to
      calculate distances of the isotopically labeled nuclei from the heme iron of each
      P450 isoform. The results were that the amide nitrogen approaches relatively
      close to the heme iron in CYP1A1 (3.64 +/- 0.51 A) whereas it is significantly
      further away (> 4.5 A) in CYP2B1. In contrast, the aryl carbon atoms ortho to the
      phenolic group of APAP approach closer to the heme iron of CYP2B1 (3.19 +/- 0.12
      A) than to the heme iron of CPY1A1 (3.66 +/- 0.30 A). The results are consistent
      with the hypothesis that CYP1A1 produces NAPQI preferentially because of closer
      proximity of the heme iron to the amide nitrogen, whereas CYP2B1 produces 3-OH
      APAP preferentially because of closer proximity of the heme iron to the phenolic
      oxygen in this isoform.

PMID- 8145238
TI  - The novel Ins(1,4,5)P3 analogue 3-amino-3-deoxy-Ins(1,4,5)P3: a pH-dependent
      Ins(1,4,5)P3 receptor partial agonist in SH-SY5Y neuroblastoma cells.
AB  - We have synthesized the first amino-substituted inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] analogue, D-3-amino-3-deoxy-myo-Ins(1,4,5)P3 (9). Although 9 is a
      full agonist at the Ca2+ mobilizing Ins(1,4,5)P3 receptor at pH 7.2 and 7.6, it
      is apparently a high intrinsic activity partial agonist at pH 6.8, releasing only
      80% of the Ins(1,4,5)P3-sensitive Ca2+ stores of SH-SY5Y cells. Additionally, 9
      was able to fully displace [3H]Ins(1,4,5)P3 from binding sites in rat cerebellum
      membranes at both pH 6.8 and 7.6, indicating a full interaction with the
      Ins(1,4,5)P3 receptor. The activity displayed by this amino analogue is
      unexpected and may be indicative of a pH-dependent conformational change in the
      amino acid residues comprising the Ins(1,4,5)P3 binding site.

PMID- 8145239
TI  - Amide hydrogen exchange in a highly denatured state. Hen egg-white lysozyme in
      urea.
AB  - The amide hydrogen exchange behaviour of hen egg-white lysozyme denatured in 8 M
      urea has been studied at pH 2.0, 20 degrees C. The observed exchange rates have
      been compared with those predicted for the same residues in a random coil
      conformation using recently published parameters for side-chain inductive and
      temperature effects on exchange catalysis. The protection factors for exchange
      obtained in this way were found to be close to unity, with 41 of the 61 residues
      that could be followed having protection factors less than 2. No protection
      factor was greater than 5. In addition, previous data for hen lysozyme denatured
      thermally and for a three-disulphide derivative, CM6-127 lysozyme, denatured at
      pH 2.0 have been reanalysed using the new reference parameters, and the
      protection factors were found to be similar to those of hen lysozyme denatured in
      8 M urea. Thus, although 1H NMR and far UV CD spectroscopy suggest that
      considerable deviations from random coil behaviour occur in these denatured
      states, such residual structure is insufficient to protect amide hydrogens
      significantly against exchange. This behaviour contrasts with that of a partly
      folded state of hen lysozyme denatured in trifluoroethanol and with that of the
      molten globule state of a homologous protein, guinea pig alpha-lactalbumin. Here
      protection factors for many amide hydrogens exceed 30 and belong to residues
      located in continuous regions of the amino acid sequence, indicating the presence
      of persistent structure. The study of hydrogen exchange in substantially
      denatured states of a protein, therefore, provides a basis for the interpretation
      of protection factors in partially folded states.

PMID- 8145240
TI  - Deletion analysis of the lambda tR1 termination region. Effect of sequences near
      the transcript release sites, and the minimum length of rho-dependent
      transcripts.
AB  - In order to determine how much of the natural sequence is required for function
      of the lambda tR1 rho-dependent terminator, and to determine the minimum length
      required, we made two deletion series of a tR1 derivative that contains mostly
      foreign DNA, encoding C-rich RNA, substituted for the natural upstream sequences
      of tR1. We find the minimum transcript length to be 85 to 90 nucleotides,
      although an additional 10 to 25 nucleotides provide more efficient termination.
      Sequences as close as ten nucleotides to the release sites could be replaced
      without destroying termination, although termination efficiency was reduced by
      substitution of these proximal regions with DNA encoding the cytidine-rich RNA
      that is active at upstream sites. These results suggest that sequences proximal
      and distal to release sites have different functions and optimal structures for
      rho activation. We also show that two potential stem-loop structures in the tR1
      region are not essential for terminator function, or for pausing at the release
      region. The results are consistent with the model that any pause site downstream
      of DNA encoding unstructured C-rich RNA is a potential rho-dependent terminator.

PMID- 8145241
TI  - The Escherichia coli prr region encodes a functional type IC DNA restriction
      system closely integrated with an anticodon nuclease gene.
AB  - The prr locus was originally described as coding a ribonuclease that is activated
      after phage T4 infection to cut within the anticodon of a specific tRNA,
      inactivating protein synthesis and thus blocking phage development. Wild-type T4
      phage has two genes coding the enzymes polynucleotide kinase and RNA ligase,
      whose only function seems to be to repair the damage done by the anticodon
      nuclease. As the only apparent function of the prr ribonuclease is to combat
      phage infection, it can be considered as an RNA-based restriction enzyme. In non
      infected cells, the prr enzyme is kept inactive in a complex with three other
      proteins which were predicted on the basis of DNA homologies to be the subunits
      of a type IC DNA restriction and modification system. Unlike other type IC
      systems so far characterized, prr is chromosomally rather than plasmid coded.
      However, sequences upstream from prr also have homology with sequences from the
      plasmid R124 and the prophage P1. We have now investigated the prr system and
      shown that it is indeed a bona fide type IC system which we call EcoprrI, and
      which is active both in vivo and in vitro. The system is fully functional even in
      the absence of the anticodon nuclease and seems to be a typical type I enzyme.
      EcoprrI recognizes the sequence CCA(N7)RTGC. One peculiarity is that, with low
      efficiency, EcoprrI will recognize and methylate variants of its recognition
      sequence such as CCT(N7)ATGC, which is methylated in one strand of the DNA only.

PMID- 8145242
TI  - Electron microscopy of cytochrome c oxidase crystals. Monomer-dimer relationship
      and cytochrome c binding site.
AB  - Cytochrome c oxidase was isolated from beef heart mitochondria by detergent
      extraction yielding two different crystal forms. Extraction with Triton
      detergents produced vesicular crystals with two-dimensional crystalline arrays of
      cytochrome c oxidase dimers while extraction with sodium deoxycholate produced
      crystalline sheets of cytochrome c oxidase monomers. The structures of both
      crystal forms were determined in two-dimensional projection along an axis normal
      to the plane of the membrane by cryoelectron microscopy of crystals embedded in
      vitreous ice (frozen-hydrated). The projection structures of unstained frozen
      hydrated monomers and of dimers are similar to the structures of the crystals in
      negative stain. The molecular outline of dimers can be approximated by a
      parallelogram 44 A by 82 A with an included angle of 80 degrees. Monomers are
      less regular consisting of two large domains with a smaller domain at one end and
      a total length of approximately 82 A. Comparison of the two structures reveals
      the orientation of cytochrome c oxidase monomers within dimers, an orientation
      which is different from earlier models of monomer-monomer interaction, and
      suggests a very close interaction between monomers when they associate to form
      dimers. The crystalline sheets of cytochrome c oxidase monomers bind tightly the
      small peripheral membrane protein substrate, cytochrome c, and this binding
      accentuates a tendency of these crystals to stack upon one another. Images of
      crystals of the cytochrome c oxidase/cytochrome c complex were analyzed by
      crosscorrelation analysis versus the monomer crystal image. Two types of two
      layer crystals have been identified. Both types have one layer rotated by 180
      degrees with respect to the other, but they differ in the shifts of origin along
      crystal axes of the two layers. Difference images formed by subtracting simulated
      multilayered crystal images (which have no bound cytochrome c) from the complex
      crystals (cytochrome c oxidase plus cytochrome c) contain one positive difference
      peak for each cytochrome oxidase monomer within a unit cell. Comparison of the
      difference peak loci among the different crystal forms is interpreted based upon
      a consensus cytochrome c binding site in the single layer cytochrome oxidase
      monomer crystal image.

PMID- 8145243
TI  - Molecular structure at 1.8 A of mouse liver class pi glutathione S-transferase
      complexed with S-(p-nitrobenzyl)glutathione and other inhibitors.
AB  - The three-dimensional crystal structure of pi class glutathione S-transferase
      YfYf from mouse liver complexed with the inhibitor S-(p-nitrobenzyl)glutathione
      has been determined at 1.8 A resolution by X-ray diffraction. In addition two
      complexes with glutathione sulphonic acid and S-hexylglutathione have been
      determined at resolutions of 1.9 and 2.2 A, respectively. The high resolution of
      the S-(p-nitrobenzyl)glutathione complex allows a detailed analysis of the active
      site including the hydrophobic (H-) subsite. The nitrobenzyl moiety occupies a
      hydrophobic pocket with its aromatic ring sandwiched between Phe8 and the
      hydroxyl group of Tyr108. An insertion of two residues Gly41 and Leu42, with
      respect to the pig enzyme, splits helix alpha B into an alpha-helix and a 3(10)
      helix. Water bridges between carbonyl oxygen atoms of the alpha-helix at its C
      terminus and the amide NH groups of the 3(10) helix at its N terminus provide
      structural continuity between these two secondary elements. Tyr7 appears to be
      the only residue close to the sulphur atom of glutathione, while three conserved
      water molecules lie in the surrounding area in all complexes. The enzyme
      mechanism is discussed on the basis of the structural analysis.

PMID- 8145244
TI  - The refined structures of a stabilized mutant and of wild-type pyruvate oxidase
      from Lactobacillus plantarum.
AB  - The crystal structure of pyruvate oxidase (EC 1.2.3.3) from Lactobacillus
      plantarum stabilized by three point mutations has been refined at 2.1 A
      resolution using the simulated annealing method. Based on 87,775 independent
      reflections in the resolution range 10 to 2.1 A, a final R-factor of 16.2% was
      obtained at good model geometry. The wild-type enzyme crystallizes isomorphously
      with the stabilized enzyme and has been analyzed at 2.5 A resolution. Pyruvate
      oxidase is a homotetramer with point group symmetry D2. One 2-fold axis is
      crystallographic, the others are local. The crystallographic asymmetric unit
      contains two subunits, and the model consists of the two polypeptide chains
      (residues 9 through 593), two FAD, two ThDP*Mg2+ and 739 water molecules. Each
      subunit has three domains; the CORE domain, the FAD domain and the ThDP domain.
      The FAD-binding chain fold is different from those of other known flavoproteins,
      whereas the ThDP-binding chain fold resembles the corresponding folds of the two
      other ThDP enzymes whose structure is known, transketolase and pyruvate
      decarboxylase. The peptide environment most likely forces the pyrimidine ring of
      ThDP into an unusual tautomeric form, which is required for catalysis. The
      structural differences between the wild-type and the stabilized enzyme are small.
      All three point mutations are at or near to the subunit interfaces, indicating
      that they stabilize the quarternary structure as had been deduced from
      reconstitution experiments.

PMID- 8145245
TI  - Comparison of the conformational stability of the molten globule and native
      states of horse cytochrome c. Effects of acetylation, heat, urea and guanidine
      hydrochloride.
AB  - The molten globule state has been assumed to be a major intermediate of protein
      folding. We compared the stability of the native and acidic molten globule states
      of horse ferricytochrome c against heat, urea and guanidine hydrochloride (Gdn
      HCl) using the intact species and species modified by various degrees of
      acetylation of the lysyl epsilon-amino groups. After acetylation, the amino
      groups cannot protonate at acidic pH. Thermal and urea-induced unfolding
      transitions measured by far-UV circular dichroism and differential scanning
      calorimetry showed that, whereas acetylation stabilizes the molten globule state
      at pH 2, it destabilizes the native state at pH 7, suggesting a difference in
      their mechanisms of conformational stability. On the other hand, the effects of
      Gdn-Hcl were remarkable. Contrary to what was expected from the thermal and urea
      induced unfolding transitions, the Gdn-HCl-induced unfolding transition of the
      native state at pH 7 was insensitive to the extent of acetylation. At pH 2, Gdn
      HCl at low concentrations stabilized the molten globule state and, at high
      concentrations, destabilized it. Consideration of the difference in the effects
      of Gdn-HCl from those of urea or heat indicated that, whereas the net positive
      charge repulsion destabilizes the molten globule state at pH 2, the local
      negative charge repulsion produced by acetylation of amino groups, and not the
      net charge, critically destabilizes the native state at pH 7. These results
      predict that, because of its ionic nature, Gdn-HCl will produce substantially
      different effects on the conformational states of some proteins compared with
      those of urea.

PMID- 8145246
TI  - Crystallization and preliminary X-ray analysis of Candida albicans phosphomannose
      isomerase.
AB  - Crystals of recombinant phosphomannose isomerase from Candida albicans have been
      obtained in a form suitable for X-ray diffraction analysis. The enzyme plays a
      key role in the biosynthesis of the mannan component of the fungal cell wall. It
      crystallizes in monoclinic space group C2, with cell dimensions a = 124.9 A, b =
      52.9 A, c = 85.9 A and beta = 127.4 degrees. The crystals diffract to Bragg
      spacings beyond 1.7 A, native data have been collected to 2.4 A and a search for
      heavy-metal derivatives is in progress. The asymmetric unit contains one molecule
      of the enzyme (M(r) approximately 49,000) with a Vm of 2.3 A3/Da.

PMID- 8145247
TI  - Single crystals of a type III antifreeze polypeptide from ocean pout.
AB  - Antifreeze protein (HPLC-2) from ocean pout was purified from serum using column
      chromatography on Sephadex G75 and reverse-phase HPLC columns. Single crystals
      were grown by batch methods at 4 degrees C from a 1.5 M solution of ammonium
      sulphate (pH 7.1). The crystals diffracted to about 2.5 A resolution at 4 degrees
      C and belong to the monoclinic space group P2(1), with cell parameters: a = 39.77
      A, b = 58.51 A, c = 30.27 A, beta = 102.28 degrees, with two molecules of 6000
      M(r) per asymmetric unit.

PMID- 8145248
TI  - Evolution of phosphagen kinase. Primary structure of glycocyamine kinase and
      arginine kinase from invertebrates.
AB  - Of the six phosphagen kinases found in animals, the primary structure is known
      only for creatine kinase. Here we report three cDNA-derived or chemically
      determined amino acid sequences of two kinds of phosphagen kinases: a
      glycocyamine kinase from the polychaete Neanthes diversicolor (Annelida) and
      arginine kinase from the abalone Nordotis madaka (Mollusca) and the shrimp
      Penaeus japonicus (Arthropoda). Like vertebrate creatine kinases are monomers.
      These enzymes consist of 350 to 390 amino acid residues, and have a calculated
      molecular mass of 39,900 to 44,500 Da. Neanthes glycocyamine kinase shows 50 to
      58% sequence similarity with vertebrate and invertebrate creatine kinases, having
      the greatest similarity (57 to 58%) with vertebrate mitochondrial creatine kinase
      isoform. It shows lower, but significant similarity (37 to 39%) with invertebrate
      arginine kinases. The sequence similarity between Nordotis and Penaeus arginine
      kinases is 51%. A phylogenetic tree constructed from 14 amino acid sequences of
      phosphagen kinases showed that they can be separated into three major clusters
      corresponding to creatine kinase, glycocyamine kinase and arginine kinase. The
      cluster of glycocyamine kinase is apparently closer to that of creatine kinase
      than arginine kinase. The cluster of creatine kinase is composed of several
      subclusters, each corresponding to three vertebrate isoforms and the invertebrate
      enzyme.

PMID- 8145249
TI  - A graphic approach to analyzing codon usage in 1562 Escherichia coli protein
      coding sequences.
AB  - The occurrence frequencies of the four bases (adenine, cytosine, guanine and
      thymine) at each of the three codon positions for 1562 Escherichia coli protein
      coding sequences have been calculated. The 1562 x 4 x 3 = 18,744 data thus
      obtained have been analyzed by a graphic method in which the four base occurrence
      frequencies at each codon position for each coding sequence are represented by a
      point in a three-dimensional space. Thus, the 18,744 data, which would otherwise
      occupy several printed pages, can be intuitively displayed by a graphy. The point
      distribution pattern for each of the three codon positions has been analyzed. The
      results of our analysis indicate that the patterns for the first two codon
      positions reflect the origin for producing native folding structures of proteins.
      We thus come to the conclusion that the distribution patterns for the first two
      codon positions should be basically species-independent, as confirmed by studies
      for a number of other species. However, the distribution pattern for the third
      codon position is species-dependent. Based on the point distribution of the third
      codon position, six collective parameters have been defined to describe the
      overall feature of the pattern concerned. These collective parameters can be
      generally used to classify different species, and hence would be a useful vehicle
      for studies in taxonomy. In addition to E. coli, the collective parameters for a
      number of other species have been calculated and analyzed.

PMID- 8145250
TI  - The secondary structure of the von Willebrand factor type A domain in factor B of
      human complement by Fourier transform infrared spectroscopy. Its occurrence in
      collagen types VI, VII, XII and XIV, the integrins and other proteins by averaged
      structure predictions.
AB  - The type A domain of the von Willebrand Factor is found also in the complement
      proteins factor B (FB), C2, CR3 and CR4, the integrins, collagen types VI, VII,
      XII and XIV, and other proteins. FB is a component of the alternative pathway of
      the complement system of immune defence, and is cleaved into the fragments Bb and
      Ba during complement activation. Bb contains a von Willebrand Factor type A (vWF)
      domain of unknown secondary structure and a serine proteinase (SP) domain,
      whereas Ba contains three short consensus repeat/complement control protein
      (SCR/CCP) domains. Fourier transform infrared (FT-IR) spectroscopy on a
      recombinant vWF domain and on FB and its Bb and Ba fragments shows a broad amide
      I band. In H2O buffer, second derivative spectra of the amide I band show
      subcomponents at 1654 to 1657 cm-1, which is typical of alpha-helix, and at 1676
      to 1685 cm-1 and 1636 to 1637 cm-1, which are typical of beta-strand. alpha-Helix
      was detected in the vWF domain, the Bb fragment and FB, and the proportion of
      alpha-helix present decreased in that order. This shows that the vWF domain
      contains appreciable amounts of alpha-helix, while the SP and SCR/CCP domains are
      almost entirely beta-sheet in their secondary structures. Quantitative
      integration of the vWF FT-IR spectrum showed that this contained 31% alpha-helix
      and 36% beta-sheet. In 2H2O buffer, the alpha-helix content in the vWF domain is
      sensitive to the solvent, while the beta-sheet content is less so. An alignment
      of 75 vWF type A sequences from 25 proteins was used for averaged secondary
      structure predictions of the total length of 206 residues by the Robson and Chou
      Fasman methods. In support of the FT-IR analysis, a total of at least five well
      predicted alpha-helices (35% of residues) and at least five well-predicted beta
      strands (21% of residues) were identified by both predictive methods, all of
      which were interspersed by regions of coil or turn conformations. Eight of the
      ten predicted alpha-helices and beta-strands form an alternating arrangement with
      each other. Since the predicted alpha-helices are mostly amphipathic, and since
      the alpha-helix FT-IR band is sensitive to solvent, the alpha-helices are
      inferred to be on the protein surface.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8145251
TI  - Crystallization of DNA polymerase II from Escherichia coli.
AB  - DNA polymerase II of Escherichia coli, an alpha-like or group B polymerase, has
      been crystallized. The crystals are orthorhombic, space group P2(1)2(1)2, with
      cell dimensions a = 94.4 A, b = 118.2 A, c = 84.2 A and diffract to at least 3.0
      A resolution. This is the first example of a group B polymerase to be
      crystallized.

PMID- 8145252
TI  - Crystals of the cell-binding module of fibronectin obtained from a series of
      recombinant fragments differing in length.
AB  - A recombinant fragment corresponding to the cell adhesion module (FNIII10) of
      human fibronectin has been crystallized at pH 8.6 from solutions containing
      polyethylene glycol as precipitant. The crystals formed in the space group P2(1)
      with a = 30.76 A, b = 35.07 A, c = 37.66 A, beta = 106.9 degrees. There is one
      molecule per asymmetric unit and the crystals diffract beyond 1.75 A resolution.
      To improve the prospects for successful crystallization of the FNIII10 module, a
      series of recombinant fragments was produced with minor differences in the length
      of N or C-terminal segments. Only one of these variants crystallized.
      Interestingly, the C-terminal residue of this variant formed stable
      intermolecular contacts with a symmetry-related molecule in the crystal lattice.

PMID- 8145253
TI  - Crystallization and preliminary X-ray analysis of phenol hydroxylase from
      Trichosporon cutaneum.
AB  - Recombinant phenol hydroxylase from the soil yeast Trichosporon cutaneum has been
      crystallized with PEG 4000 as precipitant. The crystals are monoclinic, space
      group P2(1) with cell dimensions a = 101.8 A, b = 153.0 A, c = 116.0 A and beta =
      114.8 degrees. The crystal asymmetric unit most likely contains two dimers of
      phenol hydroxylase corresponding to a packing density in the crystals of 2.54 A
      3/Da. The self-rotation function is consistent with the packing of two dimers in
      the asymmetric unit. The observed diffraction pattern extends beyond 2.8 A
      resolution and the crystals are well suited for structural analysis by X-ray
      diffraction methods.

PMID- 8145254
TI  - Analysis of the solution structure of human interleukin-4 determined by
      heteronuclear three-dimensional nuclear magnetic resonance techniques.
AB  - Human interleukin-4 (IL-4) is a member of the family of haemopoietic cytokines
      that modulate cell proliferation and differentiation within the immune system. It
      has a four-helix-bundle structure, and possesses a high degree of mobility in
      certain regions, notably in the two long loops running the length of the bundle
      in its up-up-down-down topology. Information from a variety of three-dimensional
      heteronuclear NMR experiments, including chemical shifts, coupling constants and
      NOE data, is analysed in terms of the solution structure of IL-4. In addition,
      structure calculations with and without specific restraints such as hydrogen bond
      location or torsion angle restrictions are compared in the light of the dynamic
      behaviour of the polypeptide chain. Particular emphasis is placed on defining the
      lengths and positions of secondary structure elements, and on the likely
      structural preferences within the less well ordered loop regions. The overall
      topology of IL-4 is compared with those defined in recent structure
      determinations of related proteins. This analysis is combined with recent
      mutagenesis data to propose a possible mode of interaction of IL-4 with its
      receptor.

PMID- 8145255
TI  - Glycera dibranchiata hemoglobin. X-ray structure of carbonmonoxide hemoglobin at
      1.5 A resolution.
AB  - The structure of carbonmonoxide Glycera hemoglobin has been determined to 1.5 A
      resolution by X-ray diffraction. The model, including ordered solvent, has been
      refined by the method of restrained least-squares to an R-value of 0.146. The
      positions of 1104 protein atoms and the oxygens of 155 water molecules have been
      determined with an estimated r.m.s. error of 0.10 to 0.13 A. The r.m.s. errors in
      protein geometry are 0.027 A for bond distances, 0.038 A for angle distances and
      0.012 A for deviations of planar groups from their least-squares planes. The iron
      lies exactly in the plane of the heme nitrogens and the heme is very slightly
      domed toward the proximal side. The carbon-oxygen bond in the carbon monoxide
      ligand is bent 7.9 degrees away from the normal to the plane of the heme
      nitrogens. The ligand is in close contact with, and slightly removed from the
      heme normal by distal residues Leu 58(E7) and Val62(E11). Comparison of the CO
      structure with the 1.5 A deoxy structure shows that the majority of the rather
      small structural changes occurring upon ligation are mediated by movement of the
      heme due to shortening of the five iron to nitrogen bonds. There is very little
      empty space inside the molecule, and no direct channel from the solvent into the
      heme pocket; however, rotation of the side-chain of the distal leucine residue
      Leu 58(E6) could provide a ligand pathway.

PMID- 8145256
TI  - Discrimination of intracellular and extracellular proteins using amino acid
      composition and residue-pair frequencies.
AB  - Sequences of intracellular and extracellular soluble proteins were analyzed
      statistically in terms of amino acid composition and residue-pair frequencies.
      Residue-pair frequencies were calculated for sequential separations from (n, n +
      1) to (n, n + 5), and converted into scoring parameters. Then, for each test
      protein, the single-residue and residue-pair parameters were applied to calculate
      a total score. According to our definition, a protein which yields a positive
      score is indicative of an intracellular protein, whereas a negative score implies
      an extracellular one. The parameter set was derived from 894 sequences
      constituting different protein families in the PIR database, and assessed by
      application to a test of 379 proteins. The results showed that 88% of
      intracellular and 84% of extracellular proteins were correctly assigned. The
      discrimination power was improved by about 8% in comparison with the previous
      study, which used composition data alone. Segregation of intra/extracellular
      proteins is also observed by other criteria, such as structural class
      (intracellular proteins prefer alpha and alpha/beta types and extracellular
      proteins prefer beta and alpha + beta types). Segregation by sequence was found
      to be a more reliable procedure for distinguishing intra/extracellular proteins
      than methods using structural class. Possible causes for this segregation by
      sequence are discussed.

PMID- 8145257
TI  - Structure of four-way DNA junctions containing a nick in one strand.
AB  - We have investigated the structure of the four-way helical DNA junction
      containing a single covalent discontinuity (nick) in one strand. These could
      result from either unitary strand exchange processes, or the action of nucleases
      upon a complete junction. We have employed gel electrophoresis methods to study
      the global configuration of arms in these junctions. We find that the junction
      carrying a nick in one strand undergoes a folding process in the presence of
      magnesium ion concentrations greater than 200 microM. Comparison of the
      electrophoretic mobilities of the six possible derivative junctions with two long
      and two shortened arms suggests that the folding occurs by coaxial stacking of
      pairs of helical arms, which is supported by the suppression of reactivity to
      osmium tetroxide of thymine bases at the centre of the junction. However, unlike
      the complete junction (i.e. the junction without nicked strands), the two stacked
      pairs of helices lie at a mutual angle of approximately 90 degrees. The folding
      process generates two kinds of strands; two continuous strands and two exchanging
      strands. Two isomers of the right-angled stacked structure are possible,
      depending on the selection of stacking partners; it appears that the critical
      factor determining the relative stabilities of these isomers is the location of
      the nick. Thus the nicked junctions fold into the isomer that locates the nick on
      the exchanging strand. However, if the nick is not located at the point of strand
      exchange, the junction reverts to the stacked X-structure of the complete
      junction, even if the nick is moved by a single base-pair. These results suggest
      that the exchanging strands may be significantly strained in the structure of the
      complete four-way junction, such that an interruption to the continuity at this
      position allows the two stacked helices to disengage, and rotate to an angle
      where the overall electrostatic repulsion may be lower.

PMID- 8145258
TI  - Quaternary structure of Octopus vulgaris hemocyanin. Three-dimensional
      reconstruction from frozen-hydrated specimens and intramolecular location of
      functional units Ove and Ovb.
AB  - A frozen-hydrated sample of Octopus vulgaris hemocyanin was imaged at 0 degree
      and 40 degrees tilt angle under low dose conditions by transmission electron
      microscopy. A three-dimensional reconstruction by the method of random conical
      tilt series produced a three-dimensional volume to which a D5 symmetry was
      applied. Examination of serial sections in the volume and surface representation
      at various thresholds allowed the five arches containing functional unit Ovg to
      be localized at the interdimeric subunit groove. In another set of experiments
      specific polyclonal antibodies were used to label functional units Ovb and Ove in
      the cylinder wall. The observation of the negatively stained immunocomplexes
      showed that Ovb is located in the external tiers of functional units and Ove in
      the internal tier. These results suggest that the direction of the polypeptide
      chains in the cylinder wall may be only partially antiparallel. A model of the
      quaternary structure is proposed with the following features: (1) the external
      tiers of functional units comprise four units each (Ova-d) coming from a single
      polypeptide chain; (2) the internal tier comprises two functional units from each
      polypeptide chain (Ove-f); (3) the interdimeric subunit arches connect the two
      copies of a single functional unit (Ovg) located in each polypeptide chain.

PMID- 8145259
TI  - Crystal structure of toxin II from the scorpion Androctonus australis Hector
      refined at 1.3 A resolution.
AB  - The crystal structure of toxin II from the scorpion Androctonus australis Hector
      has been refined at 1.3 A resolution using restrained least-squares methods. The
      final R-factor is 0.148 for the 13,619 reflections between 7.0 A and 1.3 A
      resolution with F > 2.5 sigma (F) and the bond length standard deviation from
      ideality is 0.017 A. Although minor changes have been introduced relative to the
      model previously refined at 1.8 A resolution, the use of higher-resolution data
      has allowed the modelling of some discrete disorder. Thus, three residues
      (including a disulphide bridge) have been built with multiple conformations.
      Occupancies were refined for the 106 solvent molecules included in the model,
      nine of them with explicit multiple sites. There is well-defined electron density
      for some of the protein hydrogen atoms in the final difference Fourier map. A
      detailed description of the toxin structure is presented, along with a comparison
      with the high-resolution structure of the related variant-3 scorpion toxin.

PMID- 8145260
TI  - Molecular phylogeny of the alphaherpesvirinae subfamily and a proposed
      evolutionary timescale.
AB  - Phylogenetic trees were derived for the Alphaherpesvirinae subfamily of the
      Herpesviridae using molecular sequences. Sequences from the families of genes
      encoding glycoprotein B, thymidine kinase, S region protein kinase, immediate
      early transcriptional regulator IE175 and ribonucleotide reductase large subunit
      were examined by means of both maximum parsimony and distance methods, and for
      both protein and DNA alignments. Trees obtained were evaluated by bootstrap
      analysis. A clear consensus tree was obtained, with most detail coming from 14
      sequences in the glycoprotein B gene set. The tree showed two avian viruses
      branching first from the lineage leading to the mammalian alphaherpesviruses. The
      mammalian viruses were split into two groups, which corresponded to the
      Simplexvirus and Varicellovirus genera. A timescale for events in
      alphaherpesvirus evolution was tested, based on the proposition that most of the
      lineages arose by ancient cospeciation with hosts. The virus phylogenetic tree
      was unambiguously compatible with cospeciation for ten of the 12 mammalian
      viruses. The tree was also supported by demonstration of an approximate
      proportionality between magnitudes of pairwise divergences of viral sequences and
      times since lineages of corresponding pairs of hosts split. On the basis of this
      timescale it was estimated that the two mammalian alphaherpesvirus groups
      diverged around the period of the mammalian radiation, and that alphaherpesviral
      genome sequences have evolved faster than those of mammals by a factor of one to
      two orders of magnitude.

PMID- 8145261
TI  - Beneficial effect of the nonselective opiate antagonist naloxone hydrochloride
      and the thyrotropin-releasing hormone (TRH) analog YM-14673 on long-term
      neurobehavioral outcome following experimental brain injury in the rat.
AB  - Neurobehavioral dysfunction following traumatic brain injury results, in part,
      from delayed biochemical changes initiated by the traumatic insult. Endogenous
      opioid peptides have been implicated as one type of neurochemical factor involved
      in the delayed pathological sequelae of central nervous system (CNS) injury,
      including brain trauma. Both opiate antagonists and thyrotropin-releasing hormone
      (TRH) and its analogs, which antagonize the physiologic effects of endogenous
      opioids, have been shown to improve cardiovascular, cerebrovascular, metabolic,
      and neurologic status following both traumatic and ischemic CNS injury. The
      present study evaluated the ability of the opiate antagonist naloxone
      hydrochloride to improve posttraumatic neurologic motor function following
      experimental fluid-percussion brain injury in the rat, and compared the
      therapeutic effectiveness of naloxone to the long-acting, centrally active TRH
      analog YM-14673. Thirty minutes following fluid-percussion brain injury of
      moderate severity, animals received an intravenous bolus of either naloxone (2.0
      mg/kg with constant infusion of 1.7 mg/kg/h, n = 8), YM-14673 (1.0 mg/kg, n = 8),
      or saline (n = 8). Although naloxone caused a modest and nonsignificant increase
      in mean arterial blood pressure (MAP); YM-14673 significantly increased MAP
      within 5 min of administration (p < 0.05), an effect that continued up to 4 h
      postinjury. Postinjury administration of both naloxone and YM-14673 caused a
      significant improvement in neurobehavioral outcome which persisted up to 4 weeks
      postinjury. These results suggest that endogenous opioid peptides may be involved
      in the pathologic response to traumatic CNS injury and that pharmacotherapies
      directed at antagonizing opioid peptides may enhance neurobehavioral recovery
      after brain injury.

PMID- 8145262
TI  - An ACTH analog minimizes cerebrovascular damage in an animal model of moderate
      brain injury.
AB  - An ACTH1-14-related analog (GMM2) was tested for efficacy in reducing the
      cerebrovascular pathology that follows moderate, closed-head injury in our rat
      model. Posttraumatic subcutaneous administration of nanomolar amounts of GMM2
      significantly minimized both the hypoperfusion and the increased blood-brain
      permeability observed 2 h following a concussion. Posttraumatic administration of
      the peptide also reduced the elevated brain water content observed at 24 and 48 h
      postinjury to nonsignificant levels. These findings complement previously
      described observations that GMM2 treatment prevents dangerous elevations of ICP
      (> 25 mm Hg) at 24 to 72 h in this model of head injury. In view of the potency
      and low toxicity of GMM2 these observation suggest that the peptide may have
      considerable clinical application in interrupting pathologic sequelae of
      traumatic brain injury.

PMID- 8145263
TI  - Interaction between free radicals and excitatory amino acids in the blood-brain
      barrier disruption after iron injury in the rat.
AB  - Excitatory amino acids and oxygen free radicals have been reported to cooperate
      in the genesis of brain injury in vivo and in vitro. In this study, we tested the
      capacity of a noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801,
      and a 21-aminosteroid, U-74006F, tirilazad mesylate, to block the opening of the
      blood-brain barrier after subarachnoid injection of FeCl2, which is believed to
      cause a primarily "pure" free radical insult. Subarachnoid injection of FeCl2
      resulted in a significant 10-fold increase in Evans blue extravasation while sham
      injection or NaCl injection had no effect. Pretreatment with either MK-801 or U
      74006F significantly reduced the FeCl2-induced increase in capillary permeability
      by 43 and 63%, respectively (p < 0.05). Combined treatment with MK-801 and U
      74006F resulted in a 65% reduction in vascular leakage that was not significantly
      greater than pretreatment with either drug alone. These results show that both
      excitatory amino acids and free radicals can damage the cerebral microvasculature
      and that an excitatory amino acid antagonist can partially protect the blood
      brain barrier after free radical-induced injury.

PMID- 8145264
TI  - Mild experimental brain injury in the rat induces cognitive deficits associated
      with regional neuronal loss in the hippocampus.
AB  - Memory dysfunction following mild human traumatic brain injury (TBI) is a common
      clinical observation, but the pathologic substrate underlying this loss of
      function has not been well-characterized. In the present study, we examined the
      effects of a mild lateral fluid percussion (FP) brain injury on memory
      dysfunction, neuronal cell loss in specific regions of the hippocampus, and
      breakdown of the blood-brain barrier (BBB). A Morris Water Maze (MWM) memory
      paradigm was used to assess memory retention in rats 42 h after lateral FP brain
      injury (n = 11) or sham injury (n = 10). At the completion of cognitive testing,
      animals were sacrificed and neuronal cell loss in the hippocampi was examined
      with Nissl staining. Immunoreactivity to anti-rat IgG was used to evaluate the
      extent of BBB disruption. A significant correlation was observed between
      posttraumatic memory scores and neuronal loss in the hilus of the dentate gyrus
      (p < 0.005). To our knowledge, these observations are the first to suggest an
      association between cognitive deficits following a mild experimental brain injury
      and neuropathological changes in the hippocampus.

PMID- 8145265
TI  - Regional patterns of blood-brain barrier breakdown following central and lateral
      fluid percussion injury in rodents.
AB  - In order to determine how fluid percussion injury (FPI) effect is distributed
      throughout the brain, and to assess the extent to which individual brain nuclei
      and regions are affected, the pattern of blood-brain barrier (BBB) breakdown was
      determined in groups with different injury cannula locations. Injury cannulas
      were placed either at midline, or 2 or 4 mm to the side. One hour following FPI,
      animals were given horseradish peroxidase (HRP) and the brains were stained using
      the TMB method. The distribution of HRP leakage varied considerably depending
      upon the location of the injury cannula, however, there were also common sites of
      leakage among these groups. Locally the cortex and hippocampus under and adjacent
      to the injury cannula were heavily affected, with a clear asymmetric effect in
      the lateral cannula groups. Common sites of leakage included the dorsal thalamus,
      septal area, pontine tegmentum, periaqueductal gray, substantia nigra, and narrow
      zones adjacent to ventricular or cisternal surfaces. The hippocampus tended to be
      involved at greater distances than the cerebral cortex. The cervicomedullary
      junction proved to be especially vulnerable to FPI with extensive HRP leakage,
      and petechial hemorrhage ranging from minor to fatal coalescent hemorrhage. A
      very narrow threshold separated these outcomes. Neurologic impairment of the
      animals correlated most directly with the extent of cervico-medullary junction
      injury. Thus FPI produces a mix of local and diffuse effects on the BBB. Injury
      at the cervicomedullary junction is a prominent effect and is the limiting factor
      in trying to establish more severe diffuse injury.

PMID- 8145266
TI  - A model for compression trauma: pressure-induced injury in cell cultures.
AB  - An increase in pressure up to 15 atm was used to condense the cellular membrane
      of cells in culture thereby eliciting a mechanical-like trauma. This trauma is
      similar to a compression-like spinal cord injury or brain injury. The cells used
      in this study were ROC-1 oligodendroglia, N1E-115 neuroblastoma, and human
      umbilical vein endothelial (HUVE) cells. Total fatty acid (FA) release and
      release of lactate dehydrogenase (LDH) into the extracellular medium were used as
      indices of cellular trauma. Pressure-induced FA release, dependent on pressure
      and pressure duration, occurred with all cell types. The level of pressure needed
      to cause the greatest increase in FA levels was 10 atm for ROC-1 cells (3 min
      duration), 15 atm for N1E-115 cells (3 min duration), and 15 atm for HUVE cells
      (10 min duration). With each cell type, the released FA were reacylated or
      metabolized between 10 and 30 min of recovery. Following a 12- to 24-h recovery
      period, N1E-115 and HUVE cells release more FA, indicating that the initial
      perturbation of the membrane was not fully reversible. LDH levels were
      significantly increased in both the N1E-115 and HUVE cultures following 24 h of
      recovery. This efflux of LDH indicates irreversible membrane damage, suggesting
      that the trauma may be irreversible at longer recovery times.

PMID- 8145267
TI  - Neuronal degeneration and spinal cavitation following intraspinal injections of
      quisqualic acid in the rat.
AB  - Microinjections of quisqualic acid were made in the spinal cord to evaluate the
      excitotoxic effects of this excitatory amino acid agonist on spinal neurons in
      the rat. Animals were divided into four groups based on post injection survival
      times of 7-49 days. Injections ranging from 0.3 to 2.0 microL of 8.3, 83, and 125
      mM quisqualic acid or normal saline were made in the lower thoracic and upper
      lumbar spinal cord. At all survival times evaluated unilateral injections of
      quisqualic acid produced unilateral or bilateral cell death and a prominent
      inflammatory reaction. In 23/25 animals spinal cavities were also observed.
      Spinal cord segments at or near quisqualate injection sites contained darkly
      stained, hypertrophied neuronal profiles, and increased staining for glial
      fibrillary acidic factor. Immunostaining for glial fibrillary acidic factor was
      especially intense in areas of neuronal degeneration and in border areas of
      spinal cavities. The results of this study suggest that the intraspinal injection
      of quisqualic acid may be an effective method to study the mechanisms of
      excitatory amino acid neurotoxicity, and the pathogenesis of spinal cavitation
      following neuronal injury.

PMID- 8145268
TI  - Fate of severed cortical projection axons.
AB  - Corticospinal neurons show a primarily degenerative response to axotomy in adult
      mammals. The long remaining proximal axon with its extensive synaptic contacts
      may contribute to the lack of initial regenerative response in this cell type. We
      examined a related group of cortical axons after lesions in the subcortical white
      matter close to their cell bodies of origin. With cholera B chain conjugated to
      horseradish peroxidase (CTB-HRP), transcallosal axons projecting into areas of a
      lesion were labeled. Animals surviving between 2 days and 4 months were examined
      with both light microscopic and ultrastructural techniques. During the first
      several days after injury, many of the axon terminals projecting into the lesion
      site had the appearance of axonal sprouts, although the majority of endings had
      the appearance of degenerating terminal swellings. By 2 weeks after injury some
      axonal sprouts had extended a short distance along the margins of the lesions,
      into overlying cortex. Four weeks after injury there is a reduction in the number
      of axons extending toward the lesion. This loss of axons appeared progressive and
      resulted in not only a loss of labeled axons, but also eventually in atrophy of
      the subcortical white matter near the lesion. In comparison to corticospinal axon
      lesions in the spinal cord or medullary pyramids, there is more extensive axonal
      sprouting and elongation after subcortical lesions. Degenerative morphological
      features still predominate after subcortical lesions and no successful trans
      lesion axonal regeneration occurs. Axonal retraction and loss are both
      accelerated and more extensive after proximal subcortical axotomy than after
      corticospinal tract lesions.

PMID- 8145269
TI  - Pesticide residues and breast cancer?

PMID- 8145270
TI  - Dense breast tissues may hold increased cancer risk for some.

PMID- 8145271
TI  - Large-scale effort tests digital mammography's potential.

PMID- 8145272
TI  - Pharmaceutical and biotechnology firms tackle health care reform.

PMID- 8145273
TI  - Stage IIIA category of non-small-cell lung cancer: a new proposal.

PMID- 8145274
TI  - Breast cancer and serum organochlorines: a prospective study among white, black,
      and Asian women.
AB  - BACKGROUND: Five small case-control studies have examined the relationship
      between exposure to organochlorines and the risk of breast cancer and have found
      inconsistent results. In these studies, organochlorine levels in breast cancer
      patients were measured after (or at most 6 months before) diagnosis. PURPOSE: We
      tested the hypothesis that organochlorines are a risk factor for breast cancer,
      using prospectively gathered data on serum levels of DDE [1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene] (the main metabolite of the pesticide DDT [2,2-bis(p
      chlorophenyl)-1,1,1-trichloroethane]) and polychlorinated biphenyls (PCBs).
      METHODS: Study subjects belonged to a cohort of 57,040 women (46,629 white, 8123
      black, and 2288 Asian) from the San Francisco Bay Area who took a multiphasic
      health examination, independent of concern about risk of breast cancer, in the
      late 1960s. At that time, a sample of blood was obtained, then frozen and stored.
      Follow-up was through December 31, 1990. We conducted a nested case-control study
      of 150 case patients and 150 matched control subjects. A random sample of 50
      women per racial/ethnic group who had been diagnosed with breast cancer more than
      6 months after the multiphasic examination (mean follow-up = 14.2 years) was
      selected, and each case patient was matched to a cancer-free control subject.
      RESULTS: Matched analyses found no differences in the case patients' and control
      subjects' serum levels of DDE (mean difference = 0.2 parts per billion [ppb]; 95%
      confidence interval [CI] = -6.7, 7.2) or PCBs (mean difference = -0.4 ppb; 95% CI
      = -0.8, 0.1). DDE levels, however, tended to be higher among black case patients
      compared with black controls (mean difference = 5.7 ppb; 95% CI = -3.3, 14.8),
      and PCBs were lower among white case patients compared with white controls (mean
      difference = -0.6 ppb; 95% CI = -1.2, -0.1). Organochlorine levels were
      significantly higher among black and Asian women compared with white women. The
      mean difference for DDE was 11.0 ppb for black women (95% CI = 4.3, 17.6) and
      12.6 ppb for Asian women (95% CI = 6.0, 19.2); for PCBs, the respective
      differences were 0.8 ppb for black women (95% CI = 0.2, 1.4) and 1.4 ppb for
      Asian women (95% CI = 0.8, 1.9). The results were not altered by adjusting for
      relevant confounders, and the lack of association between exposure to
      organochlorines and breast cancer was present regardless of length of follow-up,
      year of diagnosis, or the case patient's menopausal and estrogen-receptor status.
      CONCLUSION: The data do not support the hypothesis that exposure to DDE and PCBs
      increases risk of breast cancer. IMPLICATIONS: Future investigations must
      consider the biologic mechanisms involved and variations in exposure to chemical
      pollutants and of breast cancer incidence rates among diverse groups of women.

PMID- 8145275
TI  - Validation of the Gail et al. model for predicting individual breast cancer risk.
AB  - BACKGROUND: The Gail et al. model is considered the best available means for
      estimating an individual woman's risk of developing breast cancer. Such estimates
      are useful in decision making on the part of women, in designing prevention
      trials, and in targeting screening and prevention efforts. PURPOSE: Our purpose
      was to evaluate the ability of the model to accurately predict individual breast
      cancer risk, using a large population independent of the one from which the model
      was derived. METHODS: We compared the number of cancer cases predicted by the
      model to the actual number of cases observed in the Nurses' Health Study. The
      study population was 115,172 women who did not have breast cancer at the
      beginning of the study. Questionnaires were sent to participants every 2 years,
      seeking data on risk factors and diagnoses of breast cancer. Follow-up compliance
      was 95% over the 12-year study period. RESULTS: The model over-predicted absolute
      breast cancer risk by 33% (95% confidence interval [CI] = 28%-39%), with the
      overprediction more than twofold among premenopausal women (95% CI = 1.9-2.2),
      among women with extensive family history of breast cancer (95% CI = 1.1-3.9),
      and among women with age at first birth younger than 20 years (95% CI = 1.3-4.7).
      The correlation coefficient between observed and predicted risk was 0.67,
      indicating that the model is less than satisfactory for ranking individual levels
      of breast cancer risk. Overprediction occurred at all deciles of predicted risk.
      CONCLUSIONS: The model's performance is unsatisfactory for estimating breast
      cancer risk for individual women aged 25-61 years who do not participate in
      annual screening. Lower mammography screening rates in the Nurses' Health Study
      may account for some, but not all, of the discrepancy between observed and
      predicted cases. IMPLICATIONS: A recent modification of the model by the
      tamoxifen trial investigators is likely to have provided accurate power
      calculations. This modified form of the model should be useful for planning other
      large, population-based studies.

PMID- 8145276
TI  - Evaluation of creatine analogues as a new class of anticancer agents using
      freshly explanted human tumor cells.
AB  - BACKGROUND: The creatine kinase (CK) isozymes and their substrates, creatine and
      creatine phosphate, are believed to play a pivotal role in energy transduction in
      tissues with large, fluctuating energy demands, such as skeletal muscle, heart,
      and brain. This enzyme system may also be involved in the process of cellular
      transformation. Inhibition of tumor cell growth by creatine analogues has been
      observed and may be due to the ability of these analogues to impair cellular
      energy generation and utilization. PURPOSE: An in vitro human tumor colony
      forming assay was used to predict the clinical usefulness of creatine analogues
      as anticancer agents. METHODS: The ability of cyclocreatine (1-carboxymethyl-2
      iminoimidazolidine) and homocyclocreatine (1-carboxyethyl-2-iminoimidazolidine)
      to inhibit the growth of cells prepared from tumor samples taken directly from
      patients was evaluated by quantitative measurement of colony formation in a soft
      agar cell culture assay system. Cyclocreatine was tested in this human tumor
      colony-forming assay at concentrations ranging from 0.067 to 20 mM against 128
      tumor samples, 51 of which formed colonies in the assay and were considered
      evaluable. Homocyclocreatine was similarly tested at concentrations from 0.2 to
      20 mM against 139 tumor samples; 54 were considered evaluable. The colony-forming
      assay was also used to compare the efficacy of the creatine analogues to
      representatives from the six major classes of standard chemotherapeutics
      (alkylating agents, antimetabolites, DNA intercalators, platinum compounds,
      topoisomerase inhibitors, and tubulin-interacting agents). In addition, CK levels
      were measured in 192 tumor samples that were taken from 166 patients. RESULTS:
      Cyclocreatine and homocyclocreatine, at concentrations previously achieved in
      animal tissues (7-20 mM), had antitumor activity against 19% and 50%,
      respectively, of tumor samples that formed colonies in the assay. Cyclocreatine
      was effective against a subset of tumors sensitive to homocyclocreatine (P =
      .023; Fisher's exact test), which was the more potent creatine analogue in this
      assay (P < .001; McNemar's test). No relationships were seen between tumor
      samples sensitive to the creatine analogues and those sensitive to standard
      chemotherapeutics. Pairwise Wilcoxon rank sum tests indicated that CK activity
      was significantly higher in tumors with any growth in the colony assay compared
      with tumors that did not grow (P < .025). CONCLUSIONS: The creatine analogues,
      cyclocreatine and homocyclocreatine, effectively reduced colony formation of
      freshly explanted human tumor cells. The mechanism of action or resistance to
      these compounds seems to differ from those of standard chemotherapeutics.
      IMPLICATIONS: Creatine analogues that may alter the energy status of the tumor
      cell potentially represent promising new anticancer agents that function through
      a unique mechanism.

PMID- 8145277
TI  - Pancreatitis and pancreatic cancer: a population-based study.
AB  - BACKGROUND: Little is known about the etiology of cancer of the exocrine portion
      of the pancreas, which produces a variety of digestive enzymes. Smoking, certain
      dietary factors, and diabetes mellitus are considered to be risk factors,
      although the risk estimates are modest in most instances. A recent cohort study
      of patients with chronic pancreatitis indicated a ninefold to 16-fold increased
      risk for pancreatic cancer. PURPOSE: Our purpose was to evaluate the relationship
      between various clinical types of pancreatitis and pancreatic cancer. METHODS:
      Data for this study were collected from all inpatient medical institutions in
      Sweden from 1965 until 1983 by the Swedish National Board of Health and Welfare.
      Data were recorded on individual hospital admissions and discharges in the
      Inpatient Register. All patients with records in the Inpatient Register coded for
      acute, chronic, or unspecified pancreatitis were considered for inclusion in the
      study. A population-based cohort of 7956 patients with at least one discharge
      diagnosis of pancreatitis was monitored (up to 19 years of follow-up) for the
      occurrence of pancreatic cancer by record linkages to the Swedish Cancer Registry
      and Registry of Causes of Death. RESULTS: A total of 46 pancreatic cancers were
      diagnosed during follow-up compared with 21 expected (standardized incidence
      ratio [SIR] of 2.2; 95% confidence interval [CI] 1.6-2.9) for the Uppsala Health
      Care Region. The excess risk for women and men was similar--most pronounced
      during the first period of follow-up (2-4 years) after discharge and close to
      unity after more than 10 years of follow-up. Patients with chronic pancreatitis
      and patients with more than one discharge diagnosis of either acute or
      unspecified pancreatitis were at higher risk (SIR = 3.8; 95% CI 1.4-8.2 and SIR =
      4.8; 95% CI 1.9-9.9, respectively) compared with those with only one discharge of
      acute (SIR = 1.6; 95% CI 0.9-2.7) or unspecified (SIR = 2.1; 95% CI 1.2-3.2)
      pancreatitis. CONCLUSIONS: Our finding of a moderate excess of pancreatic cancer
      among patients with pancreatitis, especially the chronic or recurrent forms,
      supports some earlier clinical and case-control studies, but it is not consistent
      with the ninefold to 16-fold risk reported in a recent cohort study. The absence
      of an increased risk 10 years or more after first discharge for pancreatitis
      argues against a straight-forward causal relationship. Because of the relatively
      short interval between diagnosis of pancreatitis and pancreatic cancer, it is
      possible that some forms of pancreatitis are a precursor to pancreatic cancer or
      that shared risk factors for both diseases (e.g., cigarette smoking) may also be
      involved.

PMID- 8145278
TI  - Metastatic behavior of the RIF-1 murine fibrosarcoma: inhibited by hypophysectomy
      and partially restored by growth hormone replacement.
AB  - BACKGROUND: We recently demonstrated that hypophysectomy profoundly inhibits
      metastatic behavior in the MGH-OGS murine osteosarcoma model and speculated that
      this effect is related at least in part to ablation of the growth hormone (GH)
      insulin-like growth factor I (IGF-I) axis. PURPOSE: In this study, we determined
      whether the administration of GH to animals rendered GH and IGF-I deficient by
      hypophysectomy attenuates the inhibitory effects of hypophysectomy on metastatic
      behavior. METHODS: Metastatic behavior was assayed by counting visible metastases
      in lungs 3 weeks after tail vein injection of RIF-I fibrosarcoma cells to control
      mice (n = 29), hypophysectomized mice (n = 19), and hypophysectomized mice
      administered 0.05 microgram/g body weight recombinant human GH twice daily (n =
      21). RESULTS: Twenty of 21 hypophysectomized mice receiving GH, eight of 19
      hypophysectomized mice not receiving GH, and 26 of 29 controls had grossly
      visible pulmonary metastases 3 weeks after intravenous injection of 5 x 10(5)
      cells; mean numbers +/- SD of gross metastases were 38.4 +/- 11.3, 6.4 +/- 2.2,
      and 13.1 +/- 2.8 in the three groups, respectively. The presence (P < .005, chi
      square test) and number (P = .0003, Mann-Whitney U test) of metastases were
      significantly reduced in hypophysectomized hosts compared with control hosts and
      were significantly higher in hypophysectomized, GH-replaced hosts compared with
      hypophysectomized hosts (P < .001, chi-square test; P = .011, Mann-Whitney U
      test), while the difference in presence and extent of metastases between control
      and hypophysectomized, GH-replaced hosts was not statistically significant.
      CONCLUSIONS: These data support the hypothesis that the status of the host with
      respect to GH and/or GH-dependent factors such as IGF-I influences the metastatic
      behavior of certain neoplasms. IMPLICATIONS: Our results raise the possibility
      that compounds that reduce GH output or interfere with GH action, such as
      somatostatin analogues, GH antagonists, IGF antagonists, and GH-releasing hormone
      antagonists, may suppress metastatic behavior of certain neoplasms.

PMID- 8145279
TI  - Transferrin receptor expression in testis cancer.

PMID- 8145280
TI  - Greater sensitivity of human multidrug-resistant (mdr) cancer cells to
      polyunsaturated fatty acids than their non-mdr counterparts.

PMID- 8145281
TI  - Glutathione conjugation and conversion to mercapturic acids can occur as an
      intrahepatic process.
AB  - By catalyzing the reaction of electrophilic compounds with the sulfhydryl group
      of glutathione, the glutathione S-transferases play physiologically important
      roles in the detoxication of potential alkylating agents. The glutathione S
      conjugates thus formed are transported out of cells for further metabolism by
      gamma-glutamyltransferase and dipeptidases, ectoproteins that catalyze the
      sequential removal of the glutamyl and glycyl moieties, respectively. These
      ectoproteins are not found in all cells, but are localized predominantly to the
      apical surface of epithelial tissues. The resulting cysteine S-conjugates can be
      reabsorbed by specific cell types, and acetylated on the amino group of the
      cysteinyl residue by intracellular N-acetyl-transferases, to form the
      corresponding mercapturic acids (N-acetylcysteine S-conjugates). Mercapturic
      acids are then released into the circulation and delivered to the kidney for
      excretion in urine, or they may undergo further metabolism. Mercapturic acid
      biosynthesis is generally considered to be an interorgan process, with the liver
      serving as the major site of glutathione conjugation, and the kidney as the
      primary site for conversion of glutathione conjugates to cysteine conjugates.
      Cysteine conjugates formed in the kidney appear to be transported back to the
      liver for acetylation. This interorgan model of mercapturic acid synthesis is
      based largely on the interorgan distribution of the enzymes involved in their
      formation, and in particular of the enzyme gamma-glutamyltransferase. Rats have
      relatively low hepatic and high renal activities of gamma-glutamyltransferase,
      the only protein known to initiate the breakdown of glutathione S-conjugates. The
      low gamma-glutamyltransferase activity in rat liver limits the hepatic
      degradation of glutathione S-conjugates, particularly after large doses of
      xenobiotic. In contrast, hepatic gamma-glutamyltransferase is significantly
      higher in species such as rabbit, guinea pig, and dog, and as a consequence,
      nearly all of the glutathione and glutathione S-conjugates released by liver
      cells of these species is degraded within the liver. Recent studies demonstrate
      that glutathione S-conjugates synthesized within hepatocytes are secreted
      preferentially across the canalicular membrane into bile, and are broken down
      within biliary spaces to form cysteine S-conjugates. The latter are then
      reabsorbed by the liver, N-acetylated to form mercapturic acids, and reexcreted
      into bile, completing an intrahepatic pathway for mercapturic acid biosynthesis.
      The contribution of this intrahepatic pathway to overall mercapturate formation
      is dependent on dose of the electrophile, route of exposure, and the
      physicochemical properties of the glutathione S-conjugate formed, as well as the
      tissue distribution and activity of gamma-glutamyltransferase.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8145282
TI  - Urinary excretion of methylamines in men with varying intake of fish from the
      Baltic Sea.
AB  - Fish contain methylamines, especially trimethylamine N-oxide (TMAO),
      trimethylamine (TMA), and dimethylamine (DMA). Further, DMA may be formed TMA and
      TMAO. DMA is a precursor of nitrosodimethylamine (NDMA), which is a potent
      carcinogen. Levels of DMA, TMA, and TMAO in urine were used as indicators of the
      dietary exposure and in vivo formation of these amines in 44 men, representing 3
      groups with different fish consumption habits. The levels of TMA (median 0.24
      mmol/mol creatinine; range 0-2.7) and TMAO (median 38 mmol/mol creatinine; range
      8-290) were significantly associated with the weekly intake of fish (r = .47, p =
      .001, and r = .53, p = .0002, respectively), while no such relation was found for
      DMA (median 24 mmol/mol creatinine; range 5-46). Further, urinary levels of TMA
      and TMAO were dependent on recent intake of fish.

PMID- 8145283
TI  - In vitro percutaneous absorption of monosodium methanearsonate and disodium
      methanearsonate in female B6C3F1 mice.
AB  - Percutaneous absorption of monosodium [14C]methanearsonate (MSMA) and disodium
      [14C]methanearsonate (DSMA) was investigated in female B6C3F1 mice from a variety
      of exposure vehicles, including aqueous solution, solid compound, and soil. These
      chemicals are the sodium salts of methanearsonic acid, an in vivo metabolite of
      inorganic arsenic compounds, and are present in water and soil. Permeation
      experiments were carried out in vitro for 24 h using previously clipped dorsal
      skin (area = 0.64 cm2) in flow-through cells with HEPES-buffered Hanks balanced
      salt solution as receptor fluid. Applied doses of 10 (15.6), 100 (156), and 500
      (781) micrograms (micrograms/cm2) were studied in selected vehicles, and dermal
      absorption was quantitated by determining the radioactivity in the receptor fluid
      and skin following a skin surface wash to remove unpenetrated compound. Both MSMA
      and DSMA exhibited similar dermal absorption from different vehicles, and the
      rank order was aqueous solution > solid compound > soil. The degree of ionization
      of the compounds did not appear to affect their skin absorption, as both
      monobasic and dibasic forms penetrated mouse skin to the same extent from aqueous
      vehicles. An alteration in the aqueous donor volume (20, 100, and 250
      microliters) did not significantly change the total absorption of the chemicals;
      however, larger volumes significantly prolonged the time to reach maximal
      permeation rates. The major portion of the absorbed dose (53% or higher) remained
      in the skin for both chemicals. A constant fraction of the applied dose (12.4%)
      was absorbed from aqueous vehicles over the entire dosage range. Absorption of
      the chemicals was very low (< 0.5% of the dose) from soil. Even short-term (1 h)
      dermal exposure to an aqueous solution containing MSMA resulted in the
      penetration (0.66% of the dose) of this chemical. Thus, exposure vehicles have an
      important role in the in vitro dermal absorption of MSMA and DSMA in mouse skin,
      with aqueous solutions providing the greatest absorption.

PMID- 8145284
TI  - Monitoring biological effects of polychlorinated dibenzo-p-dioxins,
      dibenzofurans, and biphenyls in great blue heron chicks (Ardea herodias) in
      British Columbia.
AB  - The Canadian Wildlife Service monitors levels of polychlorinated aromatic
      hydrocarbons in great blue heron (Ardea herodias) eggs in British Columbia as
      indicators of environmental contamination. The present project assessed the
      temporal effects of environmental contamination with 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) and other polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans
      (PCDFs), and biphenyls (PCBs) on hepatic microsomal ethoxyresorufin O-deethylase
      (EROD) activities and several morphological parameters in heron hatchlings.
      Between 1990 and 1992, eggs were collected from two great blue heron colonies in
      British Columbia that had elevated levels of contamination in 1988: Vancouver in
      1990 and 1992, and Crofton in 1991. Biological parameters in the hatchlings and
      chemical contaminant levels in matched eggs from the same clutch were measured
      and compared with the findings from the same colonies studied in 1988. Levels of
      TCDD and other PCDDs and PCDFs had decreased significantly in both colonies since
      1988. A concomitant decrease in EROD activity and incidence of chick edema,
      increase in body weight, and improvement of the reproductive success of the
      Crofton colony was observed. Body, yolk-free body, stomach, and intestine
      weights, tibia wet, dry, and ash weights, and tibia length regressed negatively
      on TCDD level (p < .01; n = 54). Hepatic EROD activity regressed positively on
      TCDD level (r2 = .49; p = .00005; n = 54). Regression of these parameters on the
      sum of TCDD toxic equivalents (TEQ) resulted in similar relationships. The
      reduction in severity of the effects observed in the contaminated colonies in the
      recent collections, accompanied by the declines in levels of PCDDs and PCDFs, was
      consistent with the dose-response relationships determined in 1988.

PMID- 8145285
TI  - Stimulation of 17 beta-estradiol metabolism in MCF-7 cells by bromochloro- and
      chloromethyl-substituted dibenzo-p-dioxins and dibenzofurans: correlations with
      antiestrogenic activity.
AB  - Mixed halo- and haloalkyl-substituted dibenzo-p-dioxins (DD) and dibenzofurans
      (DF) are known environmental contaminants, although there is limited information
      on the toxic effects of these compounds in human cells. In this study
      antiestrogenicity, a property of 2,3,7,8-Cl4-DD, was investigated with a series
      of bromochloro- and chloromethyl-substituted DDs and DFs. The effects of these
      compounds on the metabolism of 17 beta-estradiol (E2) and on the estrogen
      dependent formation of multicellular foci in cultures of MCF-7 human breast cells
      were examined. Pretreatment of MCF-7 cells with 2,3,7,8-Cl4-DD induced pathways
      of E2 metabolism involving cytochrome P-450-catalyzed hydroxylation, methylation
      of the catechol estrogens, and conjugation. Several Br-Cl3-DD and Br2-Cl2-DD
      congeners with halogen substitution at the 2, 3, 7, and 8 positions also
      stimulated E2 metabolism with similar potency to that of 2,3,7,8-Cl4-DD; however,
      compounds with substitution of a methyl group for a halogen at any of these
      positions did not stimulate the metabolism of E2. For the series of compounds
      tested in MCF-7 cultures, a close correlation was observed between the
      antiestrogenicity as measured by the inhibition of estrogen-dependent
      postconfluent growth that results in focus formation and the efficacy with which
      the compounds stimulated the metabolism of E2. 2,3,7,8-TetrahaloDDs with one or
      two bromine atoms at these positions were highly antiestrogenic as determined by
      their inhibition of estrogen-dependent focus formation, whereas the methyl
      substituted polychlorinated DDs and DFs investigated did not inhibit focus
      formation. These results indicate that the 2,3,7,8-substituted mixed halo
      substituted DDs and DFs are of importance when the biologic effects of
      halogenated DD and DF congeners are considered, and provide additional evidence
      for the role of increased metabolism of E2 in the antiestrogenic effects of
      halogenated DDs and DFs.

PMID- 8145286
TI  - Soil decreases the dermal penetration of phenol in male pig in vitro.
AB  - Skin is a primary route of exposure to phenol, a major chemical found in
      hazardous waste sites. The effect of soil adsorption on the dermal
      bioavailability of phenol was assessed by applying [14C]phenol alone (P) or with
      sandy (P-S) or clay (P-C) soil to dermatomed male pig skin samples in flow
      through diffusion cells. Maximum penetration of P-S and P-C was significantly
      decreased by one-half and by two-thirds, respectively, compared to P.
      Furthermore, the penetration of phenol into receptor fluid and the amount bound
      to skin were significantly lower when phenol was adsorbed to either soil versus
      P. While less radioactivity penetrated skin with soil-adsorbed phenol treatment
      than P, significantly more radioactivity was loosely adsorbed to skin and could
      be easily washed off of the skin surface by soap and water. Only a small fraction
      (< 5%) of the chemical was metabolized by skin to hydroquinone and catechol in
      all treatment groups. The results of this study indicate that the bioavailability
      and thus the potential health risk from dermal exposure to phenol is reduced if
      the chemical is adsorbed to soil.

PMID- 8145287
TI  - Determinants of TCDD half-life in veterans of operation ranch hand.
AB  - The half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) changed significantly
      with body fat and age in 337 members of Operation Ranch Hand, the Air Force unit
      responsible for the aerial spraying of Agent Orange in Vietnam. Using paired TCDD
      measurements derived from serum collected in 1982 and in 1987, we investigated
      how TCDD half-life varied with percent body fat (PBF), relative changes in PBF,
      and age. We found that half-life increased significantly with increasing PBF and
      decreased significantly with increasing relative change in PBF and with age. The
      median observed half-life of TCDD for these 337 veterans is 11.3 yr with a
      nonparametric 95% confidence interval of 10.0-14.1 yr.

PMID- 8145288
TI  - H2O2-induced oxidative injury in rat cardiac myocytes is not potentiated by 1,1,1
      trichloroethane, carbon tetrachloride, or halothane.
AB  - Free radical-induced oxidative stress has been linked to ischemia-reperfusion
      injury of the myocardium. The .OH radical is considered the most damaging radical
      and can be increased in cells by treatment in vitro with H2O2. The purpose of the
      present study was to determine if aliphatic halocarbons enhance H2O2-induced
      oxidative injury in isolated cardiac myocytes from neonatal rats. Oxidative
      damage was assessed by measuring release of thiobarbituric acid-reactive
      substances (TBARS) from lipid peroxidation, loss of lactate dehydrogenase (LDH)
      through damaged sarcolemmal membranes, and alterations in intracellular calcium
      ([Ca2+]i) transients in electrically stimulated (1 Hz, 10 ms, 60 V) myocytes.
      H2O2 increased TBARS release and LDH leakage in a concentration-dependent (20-200
      microM) manner. Continuous suffusion with H2O2 first altered the configuration of
      [Ca2+]i transients, then eliminated them, and finally caused [Ca2+]i overload
      (basal [Ca2+]i exceeded peak systolic [Ca2+]i of control). The time to [Ca2+]i
      overload was inversely associated with concentration, and the shortest time to
      overload was obtained with 100 microM H2O2. A 1-h preincubation of myocytes with
      the iron chelator deferoxamine inhibited all effects of H2O2. 1,1,1
      Trichloroethane, carbon tetrachloride, or halothane at 1 mM significantly and
      reversibly reduced [Ca2+]i transients but did not influence TBARS release or LDH
      leakage. Simultaneous exposure of myocytes to H2O2 and halocarbons did not affect
      the myocyte response to H2O2 exposure. Results indicate that the three
      halocarbons tested do not enhance H2O2-induced oxidative injury in isolated
      cardiac myocytes.

PMID- 8145289
TI  - Cranin interacts specifically with the sulfatide-binding domain of laminin.
AB  - Cranin is a 120 kDa integral membrane glycoprotein which binds laminin under
      conditions of physiologic ionic strength in a calcium-dependent manner. Here,
      binding of cranin to laminin has been characterized using both ligand-blotting
      assays and laminin affinity bead assays. Binding was specifically inhibited by
      anti-laminin antibodies against the A chain terminal domain G, but not by several
      other region-specific antibodies. Dextran sulfate, fucoidin, and sulfatide were
      potent inhibitors of binding (50% inhibition at 0.03, 0.5, and 1.7 micrograms/ml,
      respectively); heparin was a weaker inhibitor (50% inhibition approximately 5
      micrograms/ml), and mannan and chondroitin sulfate were not inhibitory at 100
      micrograms/ml. Binding was not inhibited by lactose or the A chain peptide PA22
      2. The mobility of the broad, fuzzy cranin band was shifted after digestion with
      neuraminidase, N-glycanase, and O-glycanase, though none of these treatments
      decreased band heterogeneity nor destroyed the ability to bind laminin. Cranin
      bound to Jacalin lectin, which recognizes the Gal beta 1-3GalNAc linkage
      expressed in certain classes of mucins. These findings indicate that cranin binds
      at or near the high affinity sulfatide-binding site previously mapped to the E3
      domain of laminin, which is known to exhibit bioactivity for neural cells. In
      view of the extremely low abundance of cranin in brain membranes (approximately
      0.005%), its avid laminin-binding activity is remarkable, and strongly suggests
      that cranin may play a physiologic role in regulating specific neural cell
      interactions.

PMID- 8145290
TI  - Immediate early gene activation during the initial phases of the excitotoxic
      cascade.
AB  - Direct brain injections of the N-methyl-D-aspartate receptor agonist quinolinic
      acid (QA) trigger an excitotoxic cascade characterized by rapid neuronal death
      and glial/immune cell activation. The present study compared the timing of
      immediate early gene (IEG; c-fos, c-jun, jun-B, and zif/268) induction with the
      response of neuronal transcripts during the first 24 hr of a QA lesion within the
      rodent striatum. Following QA exposure, IEG mRNA induction periods extended from
      30 min to 24 hr. Several characteristics of this prolonged transcriptional
      response suggest that separate cell populations (neuronal vs. glial) originate
      individual IEG phases during the first day of the lesion. The first IEG phase was
      rapid and peaked at 60 min. This initial IEG phase, likely neuronal in origin,
      was dominated by robust increases in the expression of c-fos, jun-B, and zif/268
      mRNAs in contrast to small increases in c-jun expression. A second, delayed IEG
      phase was initiated after the first hour and extended to 24 hr. This IEG phase
      was more intense and continued beyond the period of neuronal survival as detected
      by the loss of neurotransmitter-specific mRNAs (preprotachykinin,
      preproenkephalin, and glutamic acid decarboxylase). During this phase, c-jun mRNA
      levels coordinately increased with c-fos. Interestingly, the transcriptional peak
      of the delayed IEG phase occurred between 4 and 12 hr, the time which
      corresponded to the rapid decline of neuronal transcripts.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8145291
TI  - Movement of embryonic chick sympathetic neurons on laminin in vitro is preceded
      by neurite extension.
AB  - Chick sympathetic neurons (E-9) are capable of moving on a laminin substrate but
      not on more adhesive substrates in vitro. The effect of laminin is dose-dependent
      and reduced by the addition of anti-laminin antibodies, whereas soluble laminin
      does not stimulate movement. The onset of neuronal movement is preceded by, and
      highly correlated with, the onset of neurite formation. The addition of 1,2
      dioctanoyl-sn-glycerol (DAG), a stimulator or protein kinase C that has been
      shown to inhibit neurite outgrowth, was found to delay both process formation and
      neuronal movement but did not affect the correlation between these two measures.
      These results support the conclusion that laminin stimulates primary neuronal
      movement in vitro and suggest that the mechanism underlying movement involves
      process formation followed by "towing" of the cell body by the advancing process.
      The similarities of this in vitro behavior to that observed in vivo suggest that
      similar mechanisms may underlie neuronal movement in the developing nervous
      system as suggested by Morest (Z Anat Entwicklungsgesch 130:265-305, 1970) and
      Liesi (EMBO J 4:1163-1170, 1985; Exp Neurol 117:103-113, 1992).

PMID- 8145292
TI  - High resolution labeling of cholinergic nerve terminals using a specific fully
      active biotinylated botulinum neurotoxin type A.
AB  - We report here on the synthesis and characterization of a fully active
      biotinylated derivative of the botulinum neurotoxin type A. Different ratios of
      biotin: botulinum toxin were tested to optimize derivatizing conditions and a
      ratio of 35:1 was selected for further experiments. The average number of biotin
      groups per toxin molecule was estimated to be 7.8, occurring at both heavy and
      light chains, and almost all externally located and easily accessible to
      recognition by streptavidin. The modified toxin retained its toxicity and its
      ability to interact with biological membranes. Apart from its suitability for
      detection in Western blots and in microtiter well plates, biotinylated botulinum
      toxin proved to be adequate for morphological labeling studies at both light and
      electron microscopy. Peroxidase histochemistry in cryostat sections of
      intoxicated rat hemidiaphragm muscles showed a distinct labeling of end-plates.
      Electron microscopy studies were performed on the electric organ of Torpedo
      marmorata using colloidal gold-conjugated streptavidin for detection. After
      intoxication of electric organ fragments with the modified toxin, gold labels
      were found associated with the presynaptic plasma membrane of nerve terminals and
      with the membrane of synaptic vesicles. Moreover, the distribution of
      biotinylated botulinum toxin binding sites over the membrane of synaptosomes
      isolated from the electric organ of Torpedo and their relationship with
      intramembrane particles were analyzed using the replica-staining label-fracture
      technique. It was found that the toxin is never associated with intramembrane
      particles.

PMID- 8145293
TI  - Cell-type specific segregation of transcriptional expression of glial genes in
      the rat peripheral neurotumor RT4 cell lines.
AB  - Four types of cells, RT4-AC (stem cell type), RT4-B and RT4-E (neuronal cell
      types), and RT4-D (glial cell type) were previously isolated from an
      ethylnitrosourea (ENU) induced rat peripheral neurotumor RT4. In a phenomenon
      termed cell-type conversion, RT4-AC spontaneously and permanently gives rise to
      the three other cell types in culture. In the RT4 system the expression of glial
      fibrillary acidic protein (GFAP) and S100 beta protein genes segregates in a cell
      type specific manner. To further characterize the RT4 family, the expression of
      four myelin-forming glial genes--P0 glycoprotein, suppressed cAMP inducible POU
      (SCIP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), and myelin basic
      protein (MBP)--has been studied in the RT4 cell lines. In addition to these
      genes, the expression of the low-affinity nerve growth factor (LNGF) receptor
      (expressed in immature Schwann cells) has been examined. We have found the
      following results. 1) The stem cell type RT4-AC and the glial cell type RT4-D
      express mRNA transcripts of P0, SCIP, and CNP (the larger form, 2.8 kb), and the
      amount of mRNA of these genes was increased by forskolin. 2) RT4-AC and RT4-D
      also express a low level of MBP mRNA upon forskolin treatment. 3) The neuronal
      cell types RT4-B and RT4-E do not express any of these myelin-forming glial genes
      with or without forskolin treatment. 4) The LNGF receptor mRNA is expressed in
      RT4-AC and RT4-D and at a lower level in RT4-B; its expression is stimulated by
      forskolin.

PMID- 8145294
TI  - Bactenecin, a leukocytic antimicrobial peptide, is cytotoxic to neuronal and
      glial cells.
AB  - Small antimicrobial peptides are abundantly produced by leukocytes. These
      peptides are active against a broad range of pathogens, notably bacteria, fungi,
      and enveloped viruses, but hardly anything is known about their physiological and
      pathophysiological relevance. We observed that bactenecin, a dodecapeptide, is
      strongly cytotoxic to rat embryonic neurons, fetal rat astrocytes and human
      glioblastoma cells. This neurotoxicity is unique to bactenecin, as a panel of
      antibacterial peptides from vertebrates and invertebrates, like defensins,
      corticostatin, indolicidin, cecropin P1, tachyplesin I, the magainins, or
      apidaecins did not impair neuronal viability.

PMID- 8145295
TI  - Members of several gene families influence survival of rat motoneurons in vitro
      and in vivo.
AB  - The survival and functional maintenance of spinal motoneurons, both during the
      period of developmental cell death and in adulthood, have been shown to be
      dependent on trophic factors. In vitro experiments have previously been used to
      identify several survival factors for motoneurons, including CNTF, LIF, and
      members of the neurotrophin, FGF, and IGF gene families. Some of these factors
      have also been shown to be active in vivo, either on chick motoneurons during
      embryonic development or on lesioned facial and spinal motoneurons of the newborn
      rat. Here we demonstrate that lesioned newborn rat facial motoneurons can be
      rescued by NT-4/5, IGF-I, and LIF. Furthermore, in contrast to chick motoneurons,
      the survival of isolated embryonic rat motoneurons can be maintained by the
      neurotrophins BDNF, NT-3, and NT-4/5. IGF-I and FGF-5 were also active in this
      system, each supporting more than 50% of the originally plated neurons. The
      responsiveness of motoneurons to multiple factors in vitro and in vivo suggests
      that motoneuron survival and function are regulated by the coordinated actions of
      members of different gene families.

PMID- 8145296
TI  - Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic
      injury to the central nervous system.
AB  - Reactive microglia and invading macrophages, which appear in brain damaged by
      stroke or trauma, secrete neuron-killing factors. This release of cytotoxic
      substances is a delayed process and is not detected until inflammatory cells
      reach a peak of reactivity by the second day after injury. Proximity to the site
      of injury and density of mononuclear phagocytes determine in part the amount of
      neurotoxic activity released by injured tissues. Moreover, drugs that suppress
      the accumulation of reactive microglia and macrophages also reduce tissue
      production of neuron poisons. Neurotoxins released by brain inflammatory cells or
      extracted directly from inflamed tissues are heat-stable, protease-resistant
      molecules < 500 daltons with actions blocked by N-methyl-D-aspartate (NMDA)
      receptor antagonists. These molecules are distinguished from free radical
      intermediates, bind to cation exchange resins, lack carboxyl moieties, and are
      separated from excitatory amino acids including glutamate or aspartate and from
      the NMDA receptor-mediated toxin quinolinic acid by ion exchange and reverse
      phase chromatography. Our data suggest that an unrecognized class of neuron
      killing molecules produced by inflammatory cells mediate the delayed neuronal
      loss associated with stroke and trauma.

PMID- 8145297
TI  - CNS white matter can be altered to support neuronal outgrowth.
AB  - Previous work has demonstrated that white matter in the adult mammalian CNS
      inhibits cell adhesion and neurite outgrowth. This phenomenon has been
      investigated most recently by culturing neurons on cryostat sections of the adult
      CNS. Employing this same technique, we have found, in accord with others, that
      neurons seldom adhere to or grow on central nervous system white matter but will
      attach and grow on gray matter. In the experiments presented here, embryonic rat
      hippocampal neurons were grown on cryostat sections from the adult rat CNS, in
      the presence of brain derived glial cocultures. It was found that the white
      matter in cryostat sections can be modified by interaction with medium
      conditioned by brain-derived glial cells. Neurons plated on sections pretreated
      by such media show significant increases in both attachment and neurite
      outgrowth. The activity contained in glial conditioned medium is likely complex
      in nature. While the majority of the activity can be eliminated by heat treatment
      and trypsinization, neural adhesion but not neurite initiation is affected by
      protease treatment. Therefore, cell attachment and neurite outgrowth may be
      regulated by different factors in the conditioned media.

PMID- 8145298
TI  - Thrombin receptor peptides induce shape change in neonatal murine astrocytes in
      culture.
AB  - Astrocytes appear star-shaped in the brain, increasingly so after injury. When
      astroglia are cultured in serum-containing medium, they exhibit a flat,
      fibroblast-like morphology. In serum-free medium, astrocytes become stellate,
      with many long processes. The serine protease alpha-thrombin mimics the effects
      of serum at subnanomolar concentrations, whereas the thrombin-inhibiting serpin,
      protease nexin I (PNI), reverses the thrombin effect. In our current experiments,
      murine neonatal spinal cord astrocytes became stellate after 4 hr in serum-free
      medium, while cortical astrocytes required 12 hr in serum-free medium for
      stellation. Astrocytes from either region flattened after 60 min in medium
      containing 3.0 to 300 pM proteolytically active human alpha-thrombin. After 12 hr
      in thrombin-containing medium, 98% of the astrocytes had a flattened morphology.
      No flattening occurred if alpha-thrombin was replaced by gamma-thrombin, which
      has its fibrinogen-recognition exosite disrupted. PNI added at 1 nM to serum
      containing medium caused stellation after 3 hr, and astroglia were 50% stellate
      by 12 hr. The effect of thrombin was mimicked by a 7-amino acid peptide (TRP-7)
      from the cleavage site of the human thrombin receptor. This peptide caused 40% of
      the astrocytes in serum-free medium to exhibit a flattened morphology after 6 hr.
      PNI had no effect on TRP-7 action on astrocytes. These results indicate that
      astrocytes possess a cell-surface receptor for thrombin, similar to that
      described for platelets, endothelial cells, and neurons.

PMID- 8145299
TI  - Platelet-derived growth factor receptor is expressed by cells in the early
      oligodendrocyte lineage.
AB  - We report the localization of PDGFR alpha mRNA (PDGFR alpha) in phenotypically
      defined cells during the first postnatal week of rat forebrain development. Using
      a method of combined immunocytochemistry and in situ hybridization we have
      demonstrated the cellular colocalization of PDGFR alpha mRNA with GD3 ganglioside
      or O4 sulfatide, phenotypic markers of oligodendrocytes, in the gray and white
      matter of the dorsal cerebral cortex at all ages studied. Population analysis of
      the PDGFR alpha +/GD3+ and PDGFR alpha+/O4+ cells revealed that three populations
      express PDGFR alpha: GD3+, GD3+/O4+, and O4+, corresponding to two lineage
      stages, progenitor and preoligodendrocyte, in oligodendrocyte development.
      Immature oligodendrocytes, identified by galactocerebroside immunoreactivity, did
      not express detectable levels of PDGFR alpha mRNA. Post-mitotic neurons,
      identified by immunoperoxidase localization of the 68 kD neurofilament, and
      astrocytes identified by S-100 or GFAP immunoreactivity were also negative for
      PDGFR alpha mRNA. The spatial and temporal expression of PDGFR alpha mRNA
      occurred in oligodendrocyte cell populations which are post-migratory and
      proliferative, but which do not express myelin proteins characteristic of post
      mitotic oligodendrocytes.

PMID- 8145300
TI  - Isolation and characterization of Bsk, a growth factor receptor-like tyrosine
      kinase associated with the limbic system.
AB  - Neuronal degeneration has been shown to be involved in various neurological
      disorders. Growth/trophic factors and their receptors are known to be important
      for the regeneration and survival of neurons. We report here the molecular
      cloning of a receptor-like protein tyrosine kinase, bsk, (for brain specific
      kinase). Bsk is highly related to the eph/elk receptor-like kinase family
      members. Northern blot analysis shows that it is expressed specifically in the
      brain, with no expression detected in adult heart, spleen, lung, liver, skeletal
      muscle, and kidney. In situ hybridization analysis of adult mouse brain sections
      indicates that bsk is expressed at high levels in the hippocampus, tenia tecta,
      indusium griseum, and the piriform cortex, major components of the limbic system
      that are important for learning and memory. In addition, elevated levels of
      expression are found in other areas of the limbic system such as the amygdala,
      medial septum, and nucleus of the diagonal band, and in the olfactory bulb, which
      has close connections to the limbic system. The highest level of expression is
      found in the CA3 region of the hippocampus and the pyramidal cell layer of the
      piriform cortex. In 16.5 day mouse embryos, bsk is expressed predominantly in the
      primordial cortex of the telencephalon. An antibody against a C-terminal peptide
      of bsk recognized a 105 kD protein in the 16.5 day embryonic head extract. Our
      analysis shows that bsk is a growth factor receptor-like protein tyrosine kinase
      and that its greatest expression in the adult brain is associated with components
      of the limbic system.

PMID- 8145301
TI  - Characterization of a Schwann cell neurite-promoting activity that directs
      motoneuron axon outgrowth.
AB  - Schwann cells support and facilitate axonal growth during development and
      successful regeneration in the peripheral nerve. In the regenerating rat sciatic
      nerve, Schwann cells provide a trophic milieu for primary sensory, sympathetic,
      and motoneurons. We have characterized a neurotrophic activity produced by adult
      rat sciatic nerve Schwann cells and a spontaneously immortal Schwann cell clone
      (iSC). This activity elicits neurite outgrowth from chick embryo explants of both
      CNS and PNS. The iSC activity has been concentrated by cation-exchange
      chromatography and compared to known neurotrophins in bioassay. Pooled bound
      fractions elicit neurite outgrowth from sympathetic, ciliary and motoneurons. In
      collagen matrix cocultures of iSC and E4 ventral horn (before motor axon
      extension to muscle targets), the iSC activity can direct the initial axonal
      extension from motoneurons. The data presented suggest that Schwann cell-produced
      activity may mediate motoneuron axonal extension before contact with their
      peripheral source of neurotrophin.

PMID- 8145302
TI  - HSP72 induction by heat stress is not universal in mammalian neural cell lines.
AB  - Heat-induced expression of 72-kDa heat shock protein (HSP72) was investigated in
      a panel of neuronal and non-neuronal cell lines by immunoblotting and
      immunocytochemistry using monoclonal antibodies directed to HSP72. By
      immunoblotting, HSP72 expression was observed in most cell lines of mouse
      (SN6.1b, CL8c4.7, NSC34.6, B2A, C2C12), rat (PC12, C-6, L3), and human (NB-1,
      GOTO, IMR-32, HeLa) origin under the heat-stressed condition. The mouse
      neuroblastoma cell line N18TG2, however, did not express HSP72 under the heat
      stressed condition. By immunocytochemistry, HSP72 was undetectable in the heat
      stressed N18TG2 cells, while it was identified in the heat-stressed SN6.1b cells,
      a clonal hybrid neuron between N18TG2 and mouse septal cholinergic neuron. By
      exposure to a priming sublethal heat shock, SN6.1b cells but not N18TG2 cells
      acquired a significant level of tolerance to a subsequent lethal heat shock.
      These results suggest that heat-induced expression of HSP72 may contribute to
      acquisition of the thermotolerant state in SN6.1b cells.

PMID- 8145303
TI  - Platelet-activating factor is a messenger in the electroconvulsive shock-induced
      transcriptional activation of c-fos and zif-268 in hippocampus.
AB  - Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine),
      undetectable in resting neural tissue, accumulates in brain during seizures. A
      hetrazepine, BN-50730, is shown here to displace [3H]PAF-specific binding from
      microsomal, but not from synaptosomal membranes, indicating selectivity for a
      high affinity intracellular binding site. Rats pretreated with BN-50730 by
      intraperitoneal or intracerebroventricular injection exhibited an inhibition of
      the electroconvulsive shock (ECS)-induced expression of c-fos and zif-268 in
      hippocampus. A much more pronounced, dose-dependent inhibition of ECS-induced zif
      268 mRNA in hippocampus by intracerebroventricular injection of BN-50730 was
      observed. It is concluded that, in the hippocampus, PAF is a mediator of the
      expression of zif-268 and, to a lesser extent, c-fos through an intracellular
      specific binding site. Thus, PAF may be a messenger in signal regulated zinc
      finger transcription factors, and in other immediate-early genes involved in long
      term synaptic plasticity changes.

PMID- 8145304
TI  - Oxygen radical-induced neurotoxicity in spinal cord neuron cultures.
AB  - The neurotoxic effects of oxygen radicals on spinal cord neuron cultures derived
      from fetal mouse have been studied. Oxygen radicals, superoxide radical and
      hydrogen peroxide, were generated by adding xanthine oxidase and hypoxanthine in
      the culture medium. Exposure of neurons to this oxygen radical-generating system
      resulted in a significant cell death and decrease of choline acetyltransferase
      (ChAT) activity in a time-dependent manner in spinal cord neuron cultures. The
      decrease in cell viability and ChAT enzyme activity induced by the oxygen
      radicals was blocked by scavengers such as superoxide dismutase (SOD), catalase,
      and tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a metal chelator.
      Antagonists of the N-methyl-D-aspartate (NMDA) receptor, including MK801 (a
      noncompetitive NMDA antagonist), D-2-amino-5-phosphonovaleric acid (APV) (a
      competitive NMDA antagonist), and 7-chlorokynurenic acid (an antagonist at the
      glycine site associated with the NMDA receptor), similarly blocked oxygen radical
      induced decrease in cell viability and ChAT activity in spinal cord neuron
      cultures. These results indicate that both oxygen radicals and excitotoxic amino
      acids were involved in the oxidant-initiated neurotoxicity of spinal cord
      neurons.

PMID- 8145306
TI  - Status of trauma patient management as measured by survival/death outcomes:
      looking toward the 21st century.
AB  - Since the focus of trauma care is to improve survival and norms have been
      established through large database studies to evaluate outcomes, the Relative
      Outcome Score provides a method to gauge treatment outcomes against perfection,
      on an ongoing basis, as long as baseline and severity mixes are standardized. The
      ROS will probably never reach 1.0 and may eventually plateau as treatment
      abilities are maximized for trauma patients, but the ROS does at least provide a
      measure to compare with the past, present and future.

PMID- 8145305
TI  - Guanosine-5'-(3-O-thio)triphosphate-mediated stimulation of phosphoinositidase C
      in solubilized rat peripheral nerve myelin and its alteration in streptozotocin
      induced diabetes.
AB  - The regulation of phosphoinositidase C (PIC) activity by guanosine-5'-(3-O
      thio)triphosphate (GTP gamma S) was characterized in a cholate-solubilized
      peripheral myelin-enriched fraction from rat sciatic nerve. The GTP analog
      maximally enhanced PIC-catalyzed hydrolysis of exogenous phosphatidylinositol-4,5
      bisphosphate (PIP2) in a dose-dependent manner only within a narrow range of
      cholate concentrations. Maximal stimulation was attained at 0.6 microM GTP gamma
      S and could be completely prevented by 1 microM guanosine-5'-(2-O
      thio)diphosphate. Neither adenylyl-imidodiphosphate nor adenosine triphosphate
      (ATP) enhanced PIC activity. Carbamoylcholine (1 mM) added together with GTP
      gamma S increased the extent of PIP2 hydrolysis over that elicited by GTP gamma S
      alone and this stimulation was blocked by the muscarinic receptor antagonist,
      atropine (50 microM). In detergent-solubilized myelin preparations from
      streptozotocin-induced diabetic rats, a higher concentration of the guanine
      nucleotide analog was required to achieve stimulation comparable to that obtained
      with corresponding preparations from normal animals. These results suggest that
      sciatic nerve myelin possesses muscarinic receptors coupled via a GTP-binding
      protein to PIC and that this system can be reconstituted in detergent-solubilized
      extracts. It is possible that the function of G proteins in cell signaling is
      impaired in experimental diabetic neuropathy.

PMID- 8145307
TI  - Organ injury scaling. IV: Thoracic vascular, lung, cardiac, and diaphragm.

PMID- 8145308
TI  - Intracompartmental sepsis in burn patients.
AB  - An uncommon cause of sepsis in patients with large burns is occult
      intracompartmental infection. A multi-institution review of 1171 burn admissions
      identified 5 patients (0.4%) who developed intracompartmental sepsis presenting
      with fever and purulent drainage or fever, erythema, and swelling on clinical
      examination. Contributing factors may have included high-volume resuscitation,
      delayed escharotomy, extravasated intraosseous infusion, cannulation-related
      arterial injury, and splinting or positioning difficulties. A high index of
      suspicion and an aggressive surgical approach facilitate successful management of
      this unusual problem.

PMID- 8145309
TI  - Gastric tonometry in multiple trauma patients.
AB  - Splanchnic ischemia, leading to intestinal mucosal damage, is thought to be
      common in patients after severe trauma. The adequacy of mucosal oxygenation can
      indirectly be determined by gastric intramucosal pH (pHi) measurement. We
      prospectively examined the posttraumatic gastric pHi values in 15 multiple trauma
      patients. In all patients gastric pHi was measured using a tonometer via the
      nasogastric route. A pHi value < or = 7.32 was used to differentiate between
      normal and low gastric pHi. Six hours after the injury four patients showed
      abnormally low pHi levels. Four other patients with normal initial pHi values
      exhibited low pHi values during one or more of the next measuring periods. Three
      of these eight patients developed major complications (two, ARDS) and two of them
      subsequently died. The seven remaining patients never had abnormal pHi levels and
      all patients had an uncomplicated recovery. Although intestinal ischemia was
      expected to be a common condition in multiple trauma patients, no consistent
      pattern of abnormal pHi measurements in the direct posttraumatic course could be
      discovered. No correlation was found between initial pHi values (at 6 hours) and
      ISS, shock, and lactic acidosis or APACHE II scores on admission. It is concluded
      that monitoring gastric pHi is useful in severely injured patients admitted to
      the ICU.

PMID- 8145310
TI  - Reliability of the arterial to end-tidal carbon dioxide gradient in mechanically
      ventilated patients with multisystem trauma.
AB  - The accuracy and reliability of the relationship between arterial and end-tidal
      carbon dioxide (PETCO2 and PaCO2), expressed as the gradient, P(a-ET)CO2, was
      assessed with 171 comparisons in nine mechanically ventilated trauma patients.
      The P(a-ET)CO2 was 14 +/- 11 mm Hg. (mean +/- standard deviation.) The positive
      correlation between PaCO2 (44 +/- 10 mm Hg) and PETCO2 (30 +/- 10 mm Hg) for the
      study population (reflected by r = 0.64, p = 0.001; but r2 = 0.41) indicated
      statistical significance, but only 40% of the changes reflected a linear
      relationship. Seventy-eight percent of individual patients had significant
      correlations of PaCO2 and PETCO2 (p < 0.02 to p < 0.001). Changes in PETCO2
      erroneously predicted the PaCO2 changes in 27% of comparisons with 15% false
      decreases and 12% false increases. Trends in P(a - ET)CO2 magnitude are not
      reliable, and concordant direction changes in PETCO2 and PaCO2 are not assured.

PMID- 8145311
TI  - Antibiotic release from impregnated pellets and beads.
AB  - Antibiotic impregnated beads are being used increasingly in the initial treatment
      of open fracture wounds, producing high antibiotic levels locally, over the first
      few days. Pellets were prepared to assess the release of the following
      antibiotics: benzylpenicillin, flucloxacillin, amoxycillin, amoxycillin
      clavulanate (Co-Amoxiclav), ciprofloxacin, imipenem, or gentamicin; the carrier
      material was either polymethylmethacrylate (PMMA) or plaster of Paris (PoP).
      Elution of antibiotic over 72 hours from the pellets in vitro was determined
      using an agar-diffusion microbiologic assay. The initial rapid release of
      antibiotic lasted 12-24 hours, with release from PoP pellets at least four-fold
      greater than that from corresponding PMMA pellets. A second phase consisted of a
      sustained but gradually diminishing elution. The release of antibiotics from PoP
      pellets compared favorably with that from the PMMA beads currently used. We
      conclude that PoP pellets may be particularly suitable for short-term
      applications such as infection prophylaxis in open fractures.

PMID- 8145312
TI  - Dynamics of interleukin 1, 2, and 6 and tumor necrosis factor alpha in multiple
      trauma patients.
AB  - The involvement of cytokines in trauma still has not been satisfactorily
      elucidated. The development of multiorgan failure, the very serious complication
      of multiple trauma with high mortality, should also be controlled by cytokines,
      endotoxin, and other mediators. We therefore prospectively studied 42 consecutive
      patients with multiple trauma admitted from June to December 1992 to the Research
      Institute for Traumatology and Surgery in Brno. Study patients were characterized
      by Injury Severity Score (ISS), Revised Trauma Score, and TRISS methodology. In
      all patients, tumor necrosis factor alpha (TNF-alpha) and interleukin (IL) 1, 2,
      and 6 levels were investigated. Of the cytokines, only IL-6 levels were elevated
      at admission and significant correlation with ISS was observed (r = 0.735; p <
      0.001). Multiple organ failure (MOF) developed in 14 patients (seven died) and it
      was not possible to predict this MOF development nor survival by initial cytokine
      levels. A significant difference was observed when IL-6 concentrations one day
      before death (423 +/- 105 pg/mL) were compared with the highest concentrations in
      MOF survivors (112 +/- 71 pg/mL; p < 0.001). This difference was found also for
      TNF (528 +/- 314 pg/mL vs. 216 +/- 165 pg/mL; p < 0.05). None of six MOF patients
      with IL-6 > 400 pg/mL survived. In conclusion, the IL-6 and TNF-alpha levels seem
      to play a significant role in multiple trauma and their late elevation in
      patients with MOF conveyed a poor prognosis. A significant correlation between
      initial IL-6 levels and ISS was observed. Other cytokines did not show dynamic
      changes during the study.

PMID- 8145313
TI  - Cardiac injuries: analysis of an unselected series of 251 cases.
AB  - Retrospective analysis was performed on the medical records of 251 patients
      treated for cardiac injuries at Highland General Hospital trauma facility in
      Alameda County, California, to identify factors that contribute to patient
      survival and predict death. Thirty-six patients (14%) had blunt injuries, 153
      patients (61%) had gunshot wounds (GSW), and 62 patients (25%) had stab wounds.
      The overall survival rate was 18.7%, GSW survival was 6.5%, stab wound survival
      was 37.1%, and blunt injury survival was 40%. Patients who arrived with some
      vital signs had 62.2% survival and patients who arrived with absent vital signs
      had < 1% survival. Stepwise multiple logistic regression analysis revealed that
      for patients with absent vital signs the only significant predictor of outcome
      was GSW as the mechanism of injury and for patients with vital signs the ISS and
      the presence of combined right and left heart injuries were significant
      independent predictors of outcome. We conclude that the routine and aggressive
      use of emergency room thoracotomy for patients with penetrating cardiac injury
      must be re-examined.

PMID- 8145314
TI  - Diving injuries: a preventable catastrophe.
AB  - During a 5-year period from January 1987 through January 1992, 58 patients were
      admitted to the Allegheny General Hospital trauma center for non-scuba, non
      suicidal diving injuries. There were 46 men and 12 women (mean age, 23 years).
      Forty-five patients were injured in swimming pools. Twenty-two patients had blood
      alcohol levels > 100 mg/dL. Cervical spine injury was the most common pathologic
      entity encountered in this group of patients. Closed head injury, pelvic
      fracture, thoracic vertebral fracture, and rib fractures were other injuries
      identified. Some patients had multiple organ failure syndrome. Aquatic
      recreational activities carry a risk for injury that is preventable. The
      mechanism, clinical data, and complications of 58 patients are presented and the
      importance of prevention is discussed.

PMID- 8145315
TI  - Treatment of Galeazzi fracture-dislocations.
AB  - Among 33 patients with a Galeazzi-type fracture-dislocation of the forearm, there
      were two children and 26 adults with a classic Galeazzi injury, and five patients
      with a Galeazzi-equivalent lesion. The worst results were obtained in type-I
      lesions. Closed reduction was primarily successful in children. The results of
      surgical treatment were much better in adults. It is advisable to treat this
      complex injury by anatomic reduction and internal fixation of the radial shaft
      fracture. Immobilization in a fully supinated position is recommended to reduce
      the dislocation of the distal radioulnar joint. Additional temporary radioulnar
      fixation with Kirschner wires is also necessary in cases of severe derangement of
      the distal radioulnar joint.

PMID- 8145316
TI  - Fracture and nonunion of the proximal tibia below an osteoarthritic knee:
      treatment by long stemmed total knee replacement.
AB  - Proximal tibial fractures below an osteoarthritic knee have a greater risk of
      nonunion. Treatment by cast immobilization alone is problematic. Internal
      fixation alone means the patient will remain handicapped because of the knee.
      Total knee replacement with a long-stemmed prosthesis treats both the fracture
      and the arthritic knee.

PMID- 8145317
TI  - Extremity gunshot wounds: Part one--Identification and treatment of patients at
      high risk of vascular injury.
AB  - Cost containment is important in this time of inner-city economic and health-care
      crisis. This paper examines patients who were treated for gunshot wounds (GSWs)
      of the extremities. During the study period 1978 through 1992, 16,316 patients
      (18,349 extremities) were treated for extremity GSWs. Nine patients with
      asymptomatic injuries in proximity to vascular structures who were treated before
      the use of duplex Doppler ultrasonography (DDU) were later found to have
      surgically treatable vascular injuries. These were identified and treated on an
      outpatient basis with no long-term morbidity or mortality. With the advent of
      DDU, asymptomatic vascular injuries were no longer missed. A conservative
      estimate of the cost savings from this study is more than $47,000,000.00. The use
      of DDU and the enclosed protocols for treating asymptomatic extremity wounds
      prevented 16,450 needless angiograms, with an additional savings of
      $32,900,000.00, for a total savings of more than $79,900,000.00. With a more
      liberal use of DDU and angiography to eliminate the rare missed vascular injuries
      (0.09%), and the use of protocols to analyze patients with asymptomatic injuries,
      many extremity GSW victims (79% in this study) can be safely treated as
      outpatients, eliminating the need for expensive in-hospital observation.

PMID- 8145318
TI  - Blood transfusions: for the thermally injured or for the doctor?
AB  - BACKGROUND: Because of the inherent risks of blood transfusions, including the
      transmission of viral and other infectious diseases, it is important to re
      evaluate blood transfusion policies. METHODS: The present study compared the
      results of a new selective transfusion policy in which patients were not
      transfused unless their hemoglobin levels went below 6-6.5 g/dL versus our
      previous routine transfusion policy in which the hemoglobin levels were routinely
      maintained at 10 g/dL. The selectively transfused group consisted of 14 patients
      with a mean +/- SD burn size of 28% +/- 11%, while the routinely transfused group
      consisted of 38 clinically comparable patients with a mean burn size of 26% +/-
      12%. RESULTS: The patients managed by selective transfusion received fewer
      transfusions (2.1 +/- 1.7 units) during their hospital stay than patients
      transfused routinely (7.4 +/- 7.6 units) (p < 0.007) and were less likely to
      receive maintenance transfusions (4 of 29 total units versus 116 of 282 total
      units) (p < 0.004). No adverse hemodynamic or other adverse effects related to
      limiting blood transfusions in the selectively transfused group was noted.
      CONCLUSION: Routinely transfused patients, on average, received over 5 units more
      blood than the selective group without any apparent clinical benefit. Thus, the
      results of this pilot study support a policy of selective blood transfusions in
      burn patients.

PMID- 8145319
TI  - A comparison of transferred versus direct admission orthopedic trauma patients.
AB  - Trauma patients with orthopedic injuries transferred to Harborview Medical Center
      (HMC) were compared with all trauma patients directly admitted to HMC and with a
      set of matched controls regarding injury Severity Score (ISS) and age, if > or =
      50 years old. Groups were compared on ISS, Revised Trauma Score (RTS), ICU stay,
      length of stay (LOS), total charges, reimbursement, payors, and outcome.
      Comparison of all transferred patients and directly admitted patients showed
      significant differences in ISS, LOS, ICU stay, and total charges. Despite a
      higher ISS, transferred patients had no differences in RTS or survival outcome.
      Comparison of matched transferred patients and directly admitted patients on ISS
      and age if > or = 50 years old showed a statistically significant increase in
      LOS, reimbursement, and charges. The survival rate of all transferred and
      directly admitted trauma patients was approximately 95% for both groups despite a
      slightly higher degree of injury in transferred patients. The reimbursement rate
      for both groups was low, 65% for transferred patients and 59% for directly
      admitted patients. The percentage of transfer patients on Medicaid was 34% and
      for direct admissions was 37% (p = 0.552). This is a large percentage of indigent
      care, since only 8.1% of Washington State residents are Medicaid dependent.

PMID- 8145320
TI  - Analysis of recurrent process errors leading to provider-related complications on
      an organized trauma service: directions for care improvement.
AB  - Complications in trauma care occur because of provider-related or patient disease
      related events. Strictly defined standardized definitions of both types of
      complications are needed to develop strategies for problem resolution. The
      frequency and characteristics of 135 disease-related and provider-related
      complications were examined for a 3-year period in a level I university trauma
      service in all patients meeting Major Trauma Outcome Study (MTOS) criteria.
      Provider-related complications were analyzed for recurrent process errors to be
      targeted for corrective action. Complication events occurred in 2764 of 3327
      patients, with provider-related complications in 759. Twenty-three percent (175)
      of complications were judged unjustified and 16 patterns of recurrent process-of
      care errors were identified. Delay in trauma team activation was caused by
      insensitivity of field triage protocols and inadequate recognition of injury
      patterns. Delays in diagnosis or surgery were caused by inadequate performance of
      standard work-up, inadequate recognition of injury severity by providers,
      diagnostic procedure interpretation errors, and errors in prioritizing the order
      of diagnostic procedures. Errors in technique were attributed to inexperience,
      haste, unfamiliarity with devices, lack of developed institutional techniques,
      and failure of providers to use recognized endpoints. Errors in judgment were
      attributed to failure to access available patient information, proceeding despite
      available information, and failure to utilize available care guidelines. Further
      reduction in provider-related morbidity in an organized trauma system requires
      this type of analysis, which identifies the need to change the process of care
      through education or adjustment of protocols for standardization care delivery in
      addition to the traditional focus on outcomes.

PMID- 8145321
TI  - Is computed tomographic grading of splenic injury useful in the nonsurgical
      management of blunt trauma?
AB  - Seventy adult and pediatric patients with blunt splenic injury were managed
      nonsurgically using previously published clinical criteria without regard to the
      appearance of the spleen on computed tomographic (CT) scans. Seven patients (10%)
      who underwent delayed surgery were considered failures of nonsurgical therapy;
      all recovered after total splenectomy. Two radiologists, blinded to patient
      outcome, retrospectively reviewed the admission CT scans of all 70 patients and
      graded them according to three published scoring systems. Higher grades of
      splenic injury on CT were not associated with an increased risk of failure
      (Fisher's exact test, p > 0.05). Nine of ten patients with very high scores on
      each of the scales were successfully managed without surgery; conversely, three
      patients with very low scores required urgent surgery. An elevated Injury
      Severity Score significantly increased the risk of failure of nonsurgical
      management (Chi-square test of trend, p = 0.001). No failures occurred in
      patients under age 17 years. Our data support the hypothesis that properly
      selected patients can be safely observed regardless of the magnitude of splenic
      injury on CT scans. A decision to undergo early exploration should be based on
      clinical criteria, including the patient's age and associated injuries.

PMID- 8145322
TI  - Advanced trauma life support program increases emergency room application of
      trauma resuscitative procedures in a developing country.
AB  - Over a 9-year period (July 1981-December 1985--pre-ATLS period; January 1986-June
      1990--post-ATLS period), the hospital charts of 813 trauma patients with ISS > or
      = 16 were reviewed (n = 413, pre-ATLS and n = 400, post-ATLS) in order to assess
      the impact of the ATLS program. The frequency of endotracheal intubation (ET),
      nasogastric tube insertion (NG), intravenous access (i.v.), Foley catheterization
      of the bladder (Foley) and chest tube insertion (CT) were compared by Pearson Chi
      square analysis. Overall, pre-ATLS vs. post-ATLS frequencies (%) were 83.5 vs.
      65.3 for ET, 97.3 vs. 98.0 for i.v., 74.6 vs. 96.3 for Foley, 68.3 vs. 91.3 for
      NG, and 18.4 vs. 47.0 for CT. In the emergency room these frequencies (%) were
      26.1 vs. 36.4 for ET, 98.8 vs. 98.7 for i.v., 11.0 vs. 97.1 for Foley, 3.2 vs.
      95.9 for NG, and 3.9 vs. 95.2 for CT. The differences in the application of these
      life saving procedures between the pre-ATLS and post-ATLS periods were
      statistically significant (p < 0.05) except i.v. access, which showed no
      difference between the pre-ATLS and post-ATLS groups. Of the patients with severe
      chest injuries (AIS > or = 3) 87.7% had chest tubes post ATLS (94.4% in ER)
      compared with 48.1% pre ATLS (3.2% in ER). These differences were associated with
      significant improvement in trauma patient outcome post ATLS. We conclude that the
      frequency of lifesaving interventions, particularly in the ER, was increased post
      ATLS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145323
TI  - Analysis of a rural trauma program using the TRISS methodology: a three-year
      retrospective study.
AB  - A three-year retrospective and prospective study was conducted in the North Coast
      EMS Region of California to evaluate the effectiveness of a rural trauma program
      and its impact on patient outcome. Two hundred sixty-six patients with major
      trauma were identified. Age, hospital and prehospital Trauma Scores (TS), Revised
      Trauma Scores (RTS), Injury Severity Scores (ISS), and Mechanism of Injury (MOI)
      were recorded. Patient outcomes were evaluated using TRISS methodology. In
      addition, the z statistic and M scores were calculated and compared with baseline
      Major Trauma Outcome Study (MTOS) norms. The majority of patients were male
      (71.9%), and the mean age was 34.05 (SD +/- 20.14). Blunt trauma accounted for
      the majority of injuries (82.1%) and the primary cause was motor vehicle crashes
      (63.8%). The z (mortality) and M statistics were -2.33 (p = 0.020) and 0.66,
      respectively. Thus a significant improvement in survival rates resulted compared
      with MTOS baseline norms.

PMID- 8145324
TI  - Trauma care in Italy: evidence of in-hospital preventable deaths.
AB  - The quality of a trauma system can be assessed by the rate of preventable deaths.
      A random selected sample of 110 trauma patients was examined using both clinical
      and autopsy data. The assessors were asked the following question: If this
      patient had sustained the accident in front of the hospital in a normal working
      day, might death have been prevented? Death was found to be unavoidable in 61
      cases, in 25 cases death was classified potentially preventable; 11 cases were
      classified as clearly preventable death. The main failures of treatment were
      identified as errors and delays during the first phases of in-hospital assessment
      and care. An improvement in the pre-hospital phase will be almost useless if the
      quality of the definitive in-hospital management is not addressed.

PMID- 8145325
TI  - Conservative treatment of a traumatic subdural hematoma of the posterior fossa in
      a child: case report.
AB  - Traumatic posterior fossa hematomas are uncommon. Subdural hematomas in this
      location are probably the rarest. The natural history in acute cases is one of
      rapid deterioration and death from brain-stem compression. Rapid surgical
      intervention is indicated in acute cases. We report a case of a traumatic
      posterior fossa subdural hematoma in a 3-year-old child treated conservatively
      with a good outcome.

PMID- 8145326
TI  - Acute bleeding caused by rupture of the thyroid gland following blunt neck
      trauma: case report.
AB  - We describe a case of blunt neck trauma that resulted in extensive rupture of a
      normal thyroid gland. Our experience shows that lesions of the thyroid gland must
      be taken into diagnostic consideration after blunt neck trauma, even in the
      absence of obvious signs of injury.

PMID- 8145327
TI  - The overlooked blunt component in penetrating neck injuries: three case reports.
AB  - Three cases of penetrating neck injury associated with an unsuspected blunt
      carotid injury are reported. Attention is drawn to the possibility of this rare
      association, that can cause irreversible damage, if overlooked. Early angiogram
      and possibly duplex Doppler scanning are warranted to prevent neurologic
      sequelae.

PMID- 8145328
TI  - Magnetic resonance imaging in cervical trauma associated with ankylosing
      spondylitis: report of two cases.
AB  - Findings on magnetic resonance imaging (MRI) in two cases of traumatic cervical
      fracture associated with ankylosing spondylitis are presented. In such patients
      cervical fracture usually occurs in the lower cervical spine from hyperextension
      injuries. Classic radiologic investigations including plain films, myelography,
      and computed tomography are insufficient because of osteopenia and distorted
      anatomy: MRI is superior to other techniques.

PMID- 8145329
TI  - Blunt extraperitoneal rupture of the right hemidiaphragm: case report.
AB  - A case of blunt extraperitoneal rupture of the right hemidiaphragm and an
      accompanying abnormal hepatobiliary scan that revealed the rupture are presented.
      Associated major injuries, the fact that right-sided ruptures have less immediate
      herniation, and plugging of the defect by the liver are difficulties that can be
      encountered in establishing the diagnosis. Most diagnostic tests are not helpful
      and about half of these ruptures are found at laparotomy or thoracotomy. All
      should be closed surgically.

PMID- 8145330
TI  - Rupture of the right diaphragm following blunt trauma in an infant: case report.
AB  - Traumatic diaphragmatic rupture is a rare childhood injury and is often difficult
      to diagnose. This is particularly true in infants. We present the case of a 3
      month-old infant with traumatic rupture of the right diaphragm that became
      clinically apparent only after extubation. The diagnosis can often be made on the
      basis of chest radiography and clinical signs. Surgical treatment is required.
      Some phrenic nerve injuries can be anticipated and late sequelae may result.

PMID- 8145331
TI  - Traumatic diaphragmatic hernia presenting as an intercostal hernia: case report.
AB  - Intercostal hernias are rarely reported in the literature. We report a case of
      intercostal hernia secondary to a ruptured right hemidiaphragm and fractured
      costal margin caused by blunt trauma. The patient was ventilated at initial
      hospitalization because of rib fractures and advanced age, and the intercostal
      hernia was not evident. After physical rehabilitation treatment elsewhere, a
      painful chest wall bulge developed. A chest film and computed tomographic scan
      revealed the hernia. Surgery with a thoraco-abdominal incision in the line of the
      hernia allowed reduction of the hernial contents.

PMID- 8145332
TI  - Thoracoscopic repair of missed diaphragmatic injury in penetrating trauma: case
      report.
AB  - We report two cases of missed diaphragmatic injury which were diagnosed and
      repaired using a thoracoscopic approach. A right diaphragmatic injury sustained
      via a stab wound to the chest was diagnosed and repaired thoracoscopically using
      a stapling technique. A second patient sustained an injury to the right diaphragm
      from a gunshot wound, which was sutured thoracoscopically. Both patients
      recovered uneventfully and had shortened hospital stays in spite of the nature of
      their injury and initial delay in diagnosis. With the increase in unsuspected
      diaphragmatic injuries being reported, we feel that combined thoracoscopy and
      laparoscopy may offer a therapeutic as well as diagnostic benefit in selected
      stable patients with penetrating injuries to the upper abdomen and lower chest.
      Although this initial report is encouraging, further investigation is needed to
      determine optimal patient selection criteria as well as the cost-effectiveness of
      this approach.

PMID- 8145333
TI  - Traumatic massive air leak treated with prolonged double lumen intubation and
      high frequency ventilation: case report.
AB  - A case is presented of unilateral traumatic massive air leak successfully treated
      with prolonged double-lumen endobronchial intubation and unilateral high
      frequency intermittent positive pressure ventilation, while the "good" lung was
      ventilated conventionally. The problems encountered are described and the
      rationale for this management are discussed.

PMID- 8145334
TI  - Thoracic aortic dissection with renal artery involvement following blunt thoracic
      trauma: case report.
AB  - Blunt thoracic aortic injury most often occurs beyond the left subclavian artery
      with subsequent transection and exsanguination. We present a case of an
      unrestrained driver involved in a high-speed motor vehicle crash who had a
      traumatic mid-thoracic aortic dissection involving the orifices of both renal
      arteries, resulting in anuria. This diagnosis should be considered in the
      presence of anuria following chest trauma.

PMID- 8145335
TI  - Unrecognized intrapleural missile--a rare cause of chronic pain following gunshot
      wounds: case report.
AB  - A young farmer was disabled by chronic pain for more than one year from a free
      intrapleural missile. Radiologic evidence of missile immobility and the tendency
      to observe chronically embedded missiles led to a delay in diagnosis.
      Intrapleural foreign bodies need to be considered in the evaluation of pain
      following chest or upper abdominal gunshot wounds.

PMID- 8145336
TI  - Enhanced rim around infarcted, traumatized spleen on computed tomographic scans:
      case report.
AB  - Computed tomography is considered a reliable imaging technique when determining
      the extent of splenic injury. We present the case of a patient with a traumatic
      infarct of the spleen detected by computed tomographic scanning of the abdomen.
      During laparotomy there was an infarction of the spleen from a hilar injury in
      addition to bleeding from the splenic vein. We conclude that ongoing bleeding
      from the splenic hilar vessel can lead to a rim of enhancement around the spleen
      from contrast material. This should be taken into account when a decision is made
      for nonsurgical management.

PMID- 8145337
TI  - Handlebar hernia: case report and review of the literature.
AB  - Traumatic abdominal wall hernia (TAWH) is an uncommon injury. Handlebar hernia
      represents one type of TAWH: handlebar hernia is caused by low-energy impact
      against a small blunt object, can be detected by physical examination, and is
      infrequently associated with other significant injury. Surgical repair is
      recommended.

PMID- 8145338
TI  - Occipital condyle fracture must be considered in the pediatric population: case
      report.
AB  - To our knowledge, no case of occipital condyle fracture after minor head trauma
      in the pediatric population has been published. We report the case of a 12-year
      old girl with a Jefferson's fracture detected on x-ray films. Axial high
      resolution computed tomography and coronal reconstruction images demonstrated the
      additional occipital condyle fracture.

PMID- 8145339
TI  - An unusual case of four iliac veins injured by gunshot: case report and review of
      the literature.
AB  - Multiple injuries of iliac veins are uncommon and frequently fatal. An unusual
      case in which there were injuries of the four iliac veins by gunshot is
      described. Prompt control of hemorrhage is required. Because our patient was in
      unstable condition, ligation of the four iliac veins was performed and the
      abdomen was packed. After a complicated course, the patient was discharged after
      40 days in good condition. Although venous repair is often recommended, ligation
      in extensive injuries may be necessary, and is usually well tolerated in young,
      previously healthy individuals like our patient.

PMID- 8145340
TI  - Avulsion of the anterior-superior iliac spine in athletes: case reports.
AB  - Avulsion of the anterior-superior iliac spine rarely occurs in adolescents. The
      condition is commonly encountered in athletes. Despite the resulting caudal
      dislocation of the apophysis, the injury is as a rule treated by conservative
      means. We report on avulsion in two young athletes treated by open reduction and
      internal fixation, which enabled them to resume sports: one 3 weeks and the other
      4 weeks after the injury. Treatment by open reduction and internal fixation is
      also indicated in patients requiring a short convalescence.

PMID- 8145341
TI  - Longitudinal fracture of the sacrum: case report.
AB  - A 51-year-old woman was involved in a motor vehicle crash, sustaining multiple
      injuries including a longitudinal displaced burst fracture of the sacrum
      associated with neurologic deficits and fractures of the pelvis. A computed
      tomographic scan was valuable in properly identifying the extent of the sacral
      fracture. Because of the neurologic deficits and displacement of the sacral
      fracture, decompression of the sacral canal and attempted reduction of the sacral
      fracture and fixation of the pelvic fracture were performed. The patient's
      neurologic deficits improved, and at last follow-up examination she was
      ambulating without assistance.

PMID- 8145342
TI  - Acute ischemia of the lower legs from blunt abdominal trauma: an unusual cause of
      atheroembolism--case report.
AB  - A 79-year-old man sustained blunt abdominal trauma in an automobile crash,
      resulting in intra-abdominal bleeding and acute ischemia of the lower
      extremities. Angiography demonstrated occlusion of the popliteal arteries
      bilaterally. He died of multiple organ failure despite immediate surgical
      intervention. Pathologic examination revealed diffuse atheroembolism of the lower
      legs.

PMID- 8145343
TI  - Reconstruction of a severe grinding injury to the medial malleolus and the
      deltoid ligament of the ankle using a free plantaris tendon graft and
      vascularized gracilis free muscle transfer: case report.
AB  - Whether or not to reconstruct deltoid ligament injuries of the ankle remains
      controversial. We present a case of deltoid ligament loss and an extensive
      overlying soft tissue defect from a grinding injury. The resultant gross medial
      ankle instability and soft tissue defect necessitated deltoid ligament
      reconstruction using a free plantaris tendon graft and soft tissue coverage using
      a free muscle transfer.

PMID- 8145344
TI  - Limitations of cervical radiography in the evaluation of acute cervical trauma.

PMID- 8145345
TI  - Trauma surgeons and emergency physicians ... can we talk?

PMID- 8145346
TI  - In vitro comparison of heated saline-blood admixture with a heat exchanger for
      rapid warming of red blood cells.

PMID- 8145347
TI  - Blunt cardiac injury: in achieving a practical diagnostic classification.

PMID- 8145348
TI  - Computed tomography in the evaluation of the aorta in patients sustaining blunt
      chest trauma.

PMID- 8145349
TI  - The effectiveness of bicyclist helmets: a study of 1710 casualties.

PMID- 8145350
TI  - Pneumomediastinum.

PMID- 8145351
TI  - Lisfranc joint injuries: trauma mechanisms and associated injuries.

PMID- 8145352
TI  - Evaluation of intravenous magnesium sulfate for the treatment of hydrofluoric
      acid burns.
AB  - Hydrofluoric acid exposures to the skin can produce severe, progressive burns.
      Medical treatment of these burns is aimed at neutralizing the free fluoride ion,
      which is felt to be responsible for burn progression. Both calcium and magnesium
      will form complexes with free fluoride and have been used as topical or
      intradermal treatments in the past. This study evaluated the efficacy of
      intravenous magnesium sulfate for the treatment of hydrofluoric acid burns and
      compared this treatment to controls and burns treated with intradermal calcium
      gluconate in a rabbit model. Both treatments demonstrated a reduction in burn
      area over time, wound depth, healing time and final scar area compared to
      controls. The intravenous magnesium treatment showed trends toward improved
      outcome compared to the intradermal calcium treatment in all parameters
      evaluated, but these differences did not reach statistical significance. This
      investigation found intravenous magnesium to be an effective method for treating
      hydrofluoric acid burns. Intravenous magnesium may have significant utility for
      treating hydrofluoric acid burns that are not amenable to current therapies.

PMID- 8145353
TI  - Drug detection and trauma cause--a case control study of fatal injuries.
AB  - Although drugs are frequently detected when studied in trauma series, the
      association between specific trauma types (such as gun shot wound) and drug use
      complicates interpretation of such reports. We carried out a case control study
      of trauma deaths with drug detection matched by cause with non-drug detection
      trauma fatality controls. We studied 117 case and control pairs identified from
      medical examiner's records. By multiple logistic regression analysis, younger
      adult age (OR 3.1; 95% CI 1.5 to 6.1) and black race (OR 2.3; 95% CI 1.1 to 5.0)
      were both strongly associated with drug detection. In contrast, neither gender,
      intent (homicide, suicide or unintentional), primary trauma site, nor ethanol
      detection were significantly associated with drug detection. Our findings suggest
      that case mix variables should be considered when interpreting the drug use rates
      in trauma.

PMID- 8145354
TI  - Fatal and nonfatal methamphetamine intoxication in the intensive care unit.
AB  - Methamphetamine poisoning was confirmed in eight patients admitted to intensive
      care 1989 through 1992 because of altered mental status and hemodynamic
      instability. Four patients were male and four were female, ages 20 to 34 years.
      Five patients were addicts and three were attempted suicides. The most common
      clinical cardiovascular manifestations were tachycardia and palpitations.
      Neurological abnormalities included agitation, hallucinations, pupillary
      dilatation and muscle twitching; profuse sweating was also common. All patients
      had rhabdomyolysis and four had remarkable elevation of creatinine kinase >
      10,000 U/L. Leucocytosis was noted in seven cases. Therapy included aggressive
      circulatory support with Swan-Ganz monitoring, external cooling and other
      modalities. The three fatalities (two addicts, one suicide) presented with coma,
      shock, body temperature 39 degrees-42 degrees C, acute renal failure, metabolic
      acidosis and hyperkalemia (K 5.6-8.5 mmol/L).

PMID- 8145355
TI  - In vitro adsorption of dichlorvos and parathion by activated charcoal.
AB  - Accidental and suicidal ingestions of organophosphate compounds continue to be a
      common occurrence in Turkey. Activated charcoal administration without gastric
      emptying has been advocated as primary therapy in most acute poisoning cases,
      although some references do not recommend activated charcoal use in
      organophosphate poisoning. This study was performed to determine the in vitro
      adsorption of dimethyl dichlorovinyl phosphate (dichlorvos) and parathion by
      activated charcoal over a wide range of charcoal:organophosphate ratios (1:1,
      2.5:1, 5:1, 10:1 and 20:1, g:g). The charcoal binding ability of dichlorvos and
      parathion were studied in both pH 1.2 and pH 7 environments. The supernatant was
      extracted with n-hexane and then analyzed by gas chromatography. Each incremental
      increase in charcoal dose increased the percent adsorption of dichlorvos and
      parathion. At the 20:1 ratio, 82.8 +/- 2.0/87.3 +/- 2.9% (pH 1.2/7.0) of
      dichlorvos and 59.3 +/- 4.5/64.5 +/- 6.1% (pH 1.2/7.0) of parathion were bound by
      activated charcoal. There were no significant differences in amounts of compound
      bound in the acid and neutral solutions. Large doses of activated charcoal
      effectively bind dichlorvos and parathion in vitro. In vivo research should be
      performed to determine activated charcoal's role in organophosphate poisoning
      cases.

PMID- 8145356
TI  - Response to specific Centruroides sculpturatus antivenom in 151 cases of scorpion
      stings.
AB  - Review was made of the symptoms, treatment and outcome of 151 cases of severe
      envenomation by the scorpion Centruroides sculpturatus treated with antivenom,
      1988-1989. The most frequent symptoms were restlessness, nystagmus, paresthesiae,
      hypersalivation, fasciculation, blurred vision and dysphagia with an average of
      four symptoms. Medications before antivenom, given to about half of the subjects,
      included antihistamines, sedatives, analgesics and epinephrine. In 71% of
      patients, symptoms were relieved within 30 minutes of receiving one vial.
      Immediate hypersensitivity reactions occurred in 8%, but were generally mild.
      Skin tests had a sensitivity of 96% and specificity of 68%. Delayed reactions
      were not addressed. In conclusion, the antivenom appears safe and effective.

PMID- 8145357
TI  - Methemoglobinemia caused by the accidental contamination of drinking water with
      sodium nitrite.
AB  - Sodium nitrite is used commercially as a coloring agent, a food preservative and
      a corrosion inhibitor. Accidental poisoning usually results from the ingestion of
      contaminated food and water and causes gastrointestinal irritation,
      vasodilatation and methemoglobinemia with subsequent tissue hypoxia. We describe
      an unusual case of sodium nitrite-induced methemoglobinemia following the
      ingestion of drinking water contaminated with a corrosion inhibitor. To our
      knowledge this is the first report of such a case.

PMID- 8145358
TI  - Fatal methemoglobinemia due to inhalation of isobutyl nitrite.
AB  - Isobutyl nitrite is a popular recreational drug among both homosexuals and
      heterosexuals as it is alleged to enhance sexual pleasure and prolong orgasm. In
      contrast to the ingestion of this volatile nitrite, inhalation is associated only
      rarely with serious sequelae, though symptomatic methemoglobinemia may occur. The
      case reported is the first documented fatality from inhalation of isobutyl
      nitrite. The widespread use of isobutyl nitrite is a cause for concern and
      physicians should be aware of the potentially fatal consequence of abuse,
      particularly in those with ischemic heart disease, and its management.

PMID- 8145359
TI  - Phenothiazine treatment and respiratory distress syndrome in a child.
AB  - An 11-year-old boy who was treated with a relatively high dose of
      methotrimeprazine meleate (Levemepromazine) a phenothiazine antipsychotic drug,
      was admitted to the pediatric intensive care unit suffering from respiratory
      distress syndrome. He required intensive treatment and support for 13 days. The
      persistent effects of methotrimeprazine meleate on various organs are typical of
      the prolonged biological action of the phenothiazine metabolites. The association
      of phenothiazine overdose and respiratory distress syndrome merits consideration.

PMID- 8145360
TI  - Folinic acid and enhanced renal elimination in formic acid intoxication.
AB  - Ingestion of over 60 g of formic acid by an adult is potentially fatal. We report
      a case of a 36-year-old woman with a history of depression who ingested 110 g of
      formic acid. She survived a complicated intensive care hospitalization following
      usage of intravenous folinic acid, urinary alkalinization, intravenous furosemide
      and supportive care. We suggest a management protocol aimed at minimizing formate
      toxicity by enhancing hepatic formate degradation via the folinic acid 'one
      carbon pool' and by enhanced renal elimination of formate.

PMID- 8145362
TI  - [Therapy of early stage liver cancer].

PMID- 8145361
TI  - Inhaled nitric oxide in advanced paraquat intoxication.
AB  - No effective treatment is available for adult respiratory distress syndrome,
      pulmonary hypertension and progressive lung fibrosis in severe paraquat
      poisoning. A potentially beneficial effect of nitric oxide inhalation on the mean
      pulmonary artery pressure and gas exchange in a subject with advanced paraquat
      intoxication is reported. Eight days after the suicidal ingestion of an unknown
      dose of paraquat, a 52-year-old female had a PaO2 < or = 50 mm Hg despite
      ventilation with an FiO2 of 1 and a positive end-expiratory pressure of 14 to 18
      cm H2O. After administration of 25 ppm nitric oxide, PaO2 increased and the mean
      pulmonary artery pressure and the right-to-left shunt decreased. Discontinuation
      of nitric oxide resulted in rapid reversal. Ventilatory function was stabilized
      for three days during nitric oxide inhalation but the patient developed massive
      pleural effusions and died on d 11 during an interruption of nitric oxide
      therapy. The response of serious paraquat intoxications to nitric oxide therapy
      may merit further study. A remarkable post-mortem finding was extensive
      myonecrosis supporting prolonged muscular retention of paraquat with toxic
      myopathy or neuromyopathy as a late manifestation of paraquat toxicity.

PMID- 8145363
TI  - [Prognostic factors and the significance of gastrectomy in gastric lymphoma].
AB  - Fifty cases of primary gastric lymphoma treated at Tenri Hospital between 1975
      and 1992 were reviewed retrospectively. Histopathologically they were classified
      according to the Working Formulation into three groups: low grade 3 cases,
      intermediate grade 42 of which 34 were diffuse large cell and high grade 5. Their
      clinical stages according to the Ann Arbor staging system were as follows; Stage
      I 15 cases, Stage II 17, Stage III 5 and Stage IV 13. Twelve variables were
      tested by univariate analysis for prognosis. Significant prognostic factors were
      clinical stage, tumor depth to the gastric wall, regional lymph node involvement,
      macroscopic finding of tumor shape and surgical resectability. Important
      variables were tested by using a multiple regression, the 5 most significant
      variable being curative surgical resection. The year survival after curative
      resection was 93.8% and 25.2% for other patients (p < 0.001). In the patients
      with Stage II-disease, the greater the 'N-number' of regional lymph node
      involvement according to the General Rules for the Gastric Cancer Study was, the
      lower the survival rate was due to the difficulty for curative resection (p <
      0.05). The same curative resection is necessary for gastric lymphoma as for
      gastric cancer. In the patients with Stage III or IV disease, higher survival
      rate was achieved in the gastrectomy group than the others. In conclusion, an
      aggressive surgical intervention is warranted in the treatment of gastric
      lymphoma of any stage.

PMID- 8145364
TI  - [An infradian rhythm of weight increment velocity in patients with Crohn's
      disease during nutritional therapy].
AB  - We examined the rhythm of weight velocity in eight patients with Crohn's disease.
      In this paper we used the spline smoothing technique to study the cycle in the
      weight increment velocity curves derived from individual data during nutritional
      therapy. As a result of the weight measurement at four-day intervals, an
      infradian rhythm with the average cycle of 9.6 +/- 0.7 was recognized in all of
      the subjects in terms of the weight increment velocity. This rhythm was
      especially conspicuous in three adolescent patients with serious nutritional
      lesion. The cycle of the rhythm was unaffected by any of the following factors:
      energy intake, contents of nutritional therapy, medical examination during the
      period. Our findings of a common cycle in the process of convalescence from a low
      nutritious stage in patients with Crohn's disease suggest that, in others as
      well, the weight increment velocity might have an infradian rhythm with a kind of
      inherent periodicity.

PMID- 8145365
TI  - [An experience of transjugular intrahepatic portosystemic shunt in the treatment
      of gastroesophageal varices].
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) using an 8-mm Gianturco
      Rosch Z stent was performed in 10 patients with liver cirrhosis admitted due to
      ruptured gastroesophageal varices. The treatment was successful in 9 patients,
      and the portal pressure decreased form 25 mmHg to 17 mmHg immediately after TIPS
      and to 15 mmHg 2 weeks after TIPS. The patency of the shunt was maintained
      adequately in the patients examined 3 months after TIPS. Endoscopy 1 month after
      TIPS showed improvements in the gastroesophageal varices in all patients.
      Hemobilia and intraperitoneal bleeding were observed in 1 patient each during
      procedure. Transient jaundice was observed in 2 and increase in the blood ammonia
      level were noted in 3 (one of whom had hepatic encephalopathy) postoperatively.
      All these complications could be treated easily. TIPS which brings about an
      immediate marked reduction in the portal pressure appears to be promising as a
      new treatment for portal hypertension.

PMID- 8145366
TI  - [Analysis of blood flow in hepatic tumors by color Doppler ultrasonography].
AB  - We evaluated the diagnostic significance of blood flow pattern and velocity in
      hepatic tumors detected by color doppler ultrasonography. Fifty seven patients
      with hepatocellular carcinoma (HCC) and 12 patients with hepatic hemangioma (HEM)
      were studied with ultrasonographic apparatus equipped with color doppler system
      (Toshiba SSA-270A, 3.75MHz sector scanner). Furthermore 12 patients with HCC were
      studied repeatedly after transcatheter arterial embolization (TAE) and/or
      percutaneous ethanol injection (PEI). Blood flow was measurable in 2 of 12
      patients with HEM (17%). Pulsatile flow with low speed (7 cm/sec) and low
      amplitude was detected in one patient, and continuous flow with low speed (5
      cm/sec) in the other. Blood flow was measurable in 43 of 57 patients with HCC
      (75%). The detection rate of blood flow in HCC was significantly higher than in
      HEM. Pulsatile flow was detectable in 42 of 43 patients (98%). Average maximum
      velocity of pulsatile flow was over 40cm/sec. Analysis of blood flow after
      treatment provided us useful information on the effect of treatment. In
      conclusion, analysis of blood flow in hepatic tumors on US with color doppler
      system may provide useful information on differential diagnosis between HCC and
      HEM, the assessment of the therapeutic effect of TAE or PEI, whether additional
      treatment is required or not, and when it should be done if required.

PMID- 8145367
TI  - [Effect of bilateral truncal vagotomy on cholecystokinin release and pancreatic
      exocrine secretion in conscious rats].
AB  - The effects of bilateral truncal vagotomy on cholecystokinin (CCK) release and
      pancreatic hypersecretion produced by bile and pancreatic juice (BPJ) diversion
      were examined in conscious rats. In addition, the effect of exogenous
      administration of CCK-8 (100 pmol/kg/h) on pancreatic secretion were compared in
      rats with and without vagotomy. Rats were prepared with external bile and
      pancreatic juice fistulae and the experiment was conducted on the 4th
      postoperative day. Basal pancreatic secretion was not affected by vagotomy. CCK
      release produced by bile and pancreatic juice diversion was enhanced, whereas
      protein secretion in response to high plasma CCK was inhibited by vagotomy.
      Pancreatic secretion stimulated by intravenous infusion of 100 pmol/kg/h of CCK-8
      was also inhibited by vagotomy. These results proposed that vagal nerve is
      mandatory for the full response of pancreatic exocrine secretion to circulating
      CCK.

PMID- 8145368
TI  - [Small nodular lesions of the pancreas: differential diagnosis with ultrasound
      angiography].
AB  - Ultrasound angiography (USAG), sonographic imaging of the blood flow in an organ
      or tissue obtained by carbon dioxide infusion into the supplying artery, was
      performed on 28 pancreatic nodular lesions less than 3 cm in diameter. The
      hemodynamics of tumors observed with USAG were divided into three groups:
      hypovascular, isovascular, and hypervascular, compared with the adjacent
      pancreatic tissue. Most of hypovascular nodules were duct cell carcinoma
      (sensitivity 94.1%, specificity 90.4%), while isovascular lesion was the
      characteristic of inflammatory masses (sensitivity 100%, specificity 95.8%).
      Hypervascular cases included all of the mucin producing tumors and islet cell
      tumors but only one case of duct cell carcinoma. So you can almost exclude duct
      cell carcinoma as an diagnosis in vascular rich tumors (negative predictive value
      83.6%). These results were compared with those on conventional x-ray angiograms
      and incremental CT scans. Ultrasound angiography enabled us to detect more slight
      differences of tumor vascularity than the other modalities. Thus we conclude that
      USAG can be a useful diagnostic aid in small mass lesions of the pancreas.

PMID- 8145369
TI  - [Clinical role of ultrasound and color Doppler ultrasound in diagnosing
      pancreatic endocrine tumors].
AB  - US, EUS, color Doppler US, and color Doppler EUS were performed for five cases of
      pancreatic endocrine tumors. US was able to detect four cases of five tumors
      (80%), but could not sufficiently evaluate the internal echo. Color Doppler US
      was able to reveal the blood flows inside in only one case (25%). EUS was able to
      detect clearly all five cases (100%), and color Doppler EUS was able to reveal a
      significant amount of the internal blood flow in all cases. Color Doppler EUS was
      reflected in hypervascular findings on angiogram and proliferating vascular
      findings on histology. Therefore, ultrasound, especially EUS was useful for
      diagnosing the location of the tumor and for evaluating the internal echo,
      whereas color Doppler EUS was useful for evaluating the vascularity of the
      tumors.

PMID- 8145370
TI  - [A case of malignant lymphoma of the stomach probably arising reactive
      lymphoreticular hyperplasia].

PMID- 8145371
TI  - [A case of gastric malignant schwannoma].

PMID- 8145372
TI  - [A case of duodenal leiomyosarcoma with von Recklinghausen's disease, which was
      difficult to be differentiated from pancreatic tumor].

PMID- 8145373
TI  - [A case of juvenile polyps associated with unclassified colitis].

PMID- 8145374
TI  - [A case of liver abscess due to MRSA].

PMID- 8145375
TI  - [An autopsied case of interstitial and infectious pneumonia appeared during
      interferon treatment for C-type chronic active hepatitis].

PMID- 8145377
TI  - [Treatment of recurrent F0RC (+)-esophageal varices by heat probe method ].

PMID- 8145376
TI  - [A case report of splenic hamartoma].

PMID- 8145378
TI  - Studies on antibiotic 230 as a molluscicide.
AB  - In the course of studying molluscicidal effects of microorganisms, a
      microorganism belonging to Streptomycetaceae, Streptomyces griseolus (Strain 230)
      was isolated from soil and a certain microbial ingredient proved to have a
      molluscicidal activity. The effective substance was named antibiotic 230. As a
      result of several investigations on the antibiotic, the following chemical
      features were made clear. The chemical substance was an indol-carbazole
      heterocyclic compound, the molecular weight 446 and the molecular formula
      C28H26N4O3. The antibiotic demonstrated a molluscicidal effect against
      Oncomelania snails and their eggs both in the laboratory and in the field. The
      compound had a wide bacteriostasis spectrum and a slight toxicity to fish in
      addition to the above, but it was non-toxic to plants.

PMID- 8145379
TI  - Prevalence of antibody to Toxoplasma gondii among inhabitants under different
      geographical and climatic conditions in Hyogo Prefecture, Japan.
AB  - Sera collected from 2,564 inhabitants of different areas in Hyogo Prefecture,
      Japan, were examined for antibody to Toxoplasma gondii by enzyme-linked
      immunosorbent assay. The overall prevalence rates of male (11.6%) and female
      populations (7.6%) were significantly different (P < 0.001). The prevalence also
      depended on age of the population. Of 11 districts three, being far from the sea
      and occupied mainly by mountains with relatively high altitudes (95-195 m),
      showed a significantly lower average prevalence (5.0%) than the other districts
      with altitudes of 3-58 m, a part of which was adjacent to the sea (10.6%; P <
      0.001). The average prevalence obtained in two districts with annual rainfall of
      1,862-2,062 mm (16.8%) was significantly higher than that obtained in six
      districts with annual rainfall of 1,026-1,204 mm (8.6%; P < 0.001).

PMID- 8145380
TI  - Ionic and nonionic fluoride levels in blood of dialyzed and undialyzed patients
      with renal failure and kidney transplanted patients.
AB  - The present study revealed that the total fluoride level in human whole blood is
      closely related to the renal function. For the undialyzed patients who had not
      undergone hemodialysis, the total fluoride level in whole blood linearly
      increased with the increase of creatinine (Cr) value. The increased fluoride was
      found to be nonionic in the other blood part than serum, while the nonionic
      fluoride level in serum was almost constant. That is, the hemodialysis treatment
      finally reduced the nonionic fluoride level in the other blood part than serum.
      On the other hand, one hemodialysis treatment could excrete ionic fluoride, but
      not nonionic fluoride. These results suggest that the ionic fluoride is
      transformed to nonionic fluoride to be accumulated in other blood part than serum
      and the nonionic fluoride is transformed to the ionic fluoride to be excreted.
      Thus the accumulation of nonionic fluoride in other blood part than serum plays a
      role of the buffer in preventing a too high serum fluoride level.

PMID- 8145381
TI  - Histopathological study of congenitally diabetic yellow KK mouse lens.
AB  - Lenses of Yellow KK mice with marked obesity and diabetic symptoms were examined
      by light and electron microscopy. At 2 months of age, the entire lens appeared
      normal. At 4 months, however, epithelial cells sometimes had become necrotic and
      showed intranuclear inclusions. At 6 months, the anterior cortical fibers were
      swollen. At 8 months, the number of intranuclear inclusions of the epithelial
      cells had increased, and the posterior cortex contained densely stained cells
      among the fibers, with swollen cytoplasm. At 10 months, these cells had become
      atrophic. At 12 months, the lens cells in the posterior sutural area showed
      marked swelling, and the suture was almost separated. This animal model showed a
      slow progressive cataract in the superficial cortical zone which is similar to
      the diabetic cataract in human eyes.

PMID- 8145382
TI  - Efficacy of intravitreal hemocoagulase for control of bleeding in rabbit
      experimental model of vitrectomy.
AB  - Hemorrhage during vitrectomy for diabetic retinopathy or in the recently
      traumatized eye can complicate the surgical procedures and might cause
      termination and failure of vitrectomy in some cases. The effect of the
      hemocoagulase, Botropase, on the hemostasis of intraocular bleeding was evaluated
      in a rabbit model by cutting central retinal vessels in the medullary ray.
      Addition of the hemocoagulase (1 NIH unit/100 ml) to BSS Plus significantly
      reduced bleeding time. Immediately after vitrectomy with the use of this
      hemocoagulase, the average of the maximum amplitudes of the b-wave in
      electroretinography was normal, although the sensitivity of the electroretinogram
      was reduced by 0.1 log unit in the experimental eyes which were infused with
      hemocoagulase solution. The sensitivity showed no significant difference after
      the second postoperative day. The experimental eyes showed no abnormal findings
      histologically. Infusate containing Botropase appeared to be a useful adjunct for
      the control of intraocular bleeding during vitreous surgery.

PMID- 8145383
TI  - Blood velocity in the ophthalmic artery determined by color Doppler imaging in
      normal subjects and diabetics.
AB  - Color Doppler imaging was used to analyze the blood velocity in the ophthalmic
      artery (BVA) of 33 normal subjects and 36 diabetic patients. Maximum systolic BVA
      (Vmax), minimum end-diastolic BVA (Vmin) and Pourcelot index (RI: index of
      vascular resistance) were determined by analyzing the pulse wave of flow velocity
      in the ophthalmic artery. The coefficient of reproducibility of Vmax, Vmin and RI
      in normal subjects was 10%, 9% and 4%, respectively, when analyzed twice at one
      hour intervals. There was no significant difference in the indices of the right
      eyes compared to those of the left eyes. The averages of Vmax, Vmin and RI were
      25.4 +/- 7.6 cm/s, 6.3 +/- 2.3 cm/s and 0.75 +/- 0.052 (mean +/- SD),
      respectively. Vmax and Vmin decreased significantly with age (Vmax: r = -0.65, P
      < 0.001; Vmin: r = -0.61, P < 0.001). RI did not change with age. Vmax, Vmin and
      RI were compared between normal subjects and patients. RI was significantly
      higher in diabetics (0.775 +/- 0.047 in patients without retinopathy, 0.779 +/-
      0.084 in patients with background retinopathy and 0.786 +/- 0.081 in patients
      with preproliferative or proliferative retinopathy) than in normal subjects
      (0.728 +/- 0.054). This suggests there is a pathological increase in choroidal
      vascular resistance and/or a decrease in the diameter of the ophthalmic artery in
      diabetics.

PMID- 8145384
TI  - Distribution of the innervating neurons of pupillary dilator and tarsal muscles
      in the superior cervical ganglion.
AB  - In an experimental study using adult cats, we analyzed the distribution of the
      sympathetic postganglionic neurons in the superior cervical ganglion (SCG) which
      innervate the pupillary dilator and tarsal muscles to determine whether there are
      direct fiber projections from the spinal cord to the iridic and tarsal muscles.
      This study consisted of three experiments. In Experiments 1 and 2, respectively,
      horseradish peroxidase (HRP) was injected unilaterally into the iridic stroma or
      superior tarsal muscles. The SCG and spinal cord were then removed for
      microscopic analysis. In Experiment 3, the ganglion was examined microscopically
      after the injection of bisbezimide into the iris and of HRP into the ipsilateral
      superior tarsal muscle. Experiment 1 revealed more numerous HRP-labeled neurons
      in the rostral part than in any other region of the ipsilateral superior cervical
      ganglion. In Experiment 2, HRP-labeled neurons were evenly distributed over the
      whole ipsilateral SCG. No HRP-labeled neurons were detected in the spinal cord in
      either of these experiments. In Experiment 3, no doubly-labeled neurons were
      discernible in the ganglion. These results clearly indicate the localization of
      internal carotid nerve cells in a specific region of the SCG, and provide
      evidence for the absence of postganglionic neurons that innervate both the
      dilator muscle of the pupil and the tarsal muscles.

PMID- 8145385
TI  - Vergence eye movements facilitated by saccades.
AB  - This study was carried out to determine whether the vergence velocity is
      influenced or not by the richness in visual cues for the perception of depth and
      by the association of saccade. Vergence eye movements associated with and without
      saccades were recorded in 4 normal subjects with two CCD cameras in both dark and
      illuminated rooms. Subjects fixated between the targets, which differed in
      direction and in depth. The peak vergence velocity was 50 degrees to 90 degrees
      per second for 10 degrees vergence change and 30 degrees to 70 degrees per second
      for 5 degrees vergence change. Transient vergence change was found during
      horizontal or vertical saccade. Even after deleting this transient vergence
      change, the peak velocity of vergence became faster when it was associated with
      vertical or horizontal saccade. Trajectories of fixation locus were calculated
      when the vergence and saccade were required simultaneously. Whether or not the
      room was rich in visual cues for depth perception seemed to have no effect on
      vergence velocity. Blinking also speeded up divergence. Most eye movements in
      daily life are the combination of vergence and saccade, and this vergence
      facilitation by saccade helps to attain prompt binocular fixation on the new
      target.

PMID- 8145386
TI  - Histopathological study of pseudophakic bullous keratopathy developing after
      anterior chamber of iris-supported intraocular lens implantation.
AB  - Sixty corneal buttons excised from patients who developed pseudophakic bullous
      keratopathy after anterior chamber or iris-supported intraocular lens
      implantation were studied morphologically and statistically. The mean age of
      patients was 72.5 +/- 11.6 years. The mean interval between intraocular lens
      implantation and keratoplasty was 5.1 +/- 2.2 years. Degeneration and conversion
      of endothelial cells, abnormal proliferation of posterior collagenous layer, and
      edema of stroma and epithelium were noticed morphologically. Twenty-nine of the
      60 specimens showed a surviving endothelial cell area of less than 50%. In these
      specimens a significant increase in the thickness of the central stroma was
      recognized compared with the other 31 specimens. The number of keratocytes in the
      29 specimens had decreased significantly compared with the control. A linear
      regression study showed a significant relationship between the thickness of the
      stroma and the number of keratocytes. The keratocyte density decreased
      predominantly in the posterior part of the stroma.

PMID- 8145387
TI  - Lattice corneal dystrophy type II with familial amyloid polyneuropathy type IV.
AB  - Lattice corneal dystrophy type II with familial amyloid polyneuropathy type IV
      (Finnish type, Meretoja's syndrome, FAP-IV) has not been reported in Japan to
      date. In this study we report on 7 cases in a Japanese family which we recently
      examined. The proband, a 64-year-old man, suffering from itching in his limbs,
      impaired lip movement and dysarthria, consulted the Department of Neurology,
      University of Tokyo. Neurological examinations revealed bilateral facial,
      glossopharyngeal, vagal and hypoglossal nerve palsies, and also impaired distal
      vibratory perception. Immunohistological and biochemical studies confirmed the
      diagnosis of FAP-IV. Ophthalmological examinations showed his vision was 1.2 with
      fine lattice corneal dystrophy in both eyes. The lattice dystrophy was randomly
      scattered with short glassy lines. Corneal sensation was normal and there was no
      evidence of recurrent corneal erosion. Six family members with similar lattice
      corneal dystrophies also were suspected to be affected neurologically by FAP-IV.
      The family pedigree suggested an autosomal dominant trait of inheritance.

PMID- 8145388
TI  - Current trends in cataract and refractive surgery in Japan--1992 survey.
AB  - A survey was carried out by mail in January 1993 to investigate the current
      trends in cataract and refractive surgery in Japan. A questionnaire was sent to
      members of the Japanese Intraocular Lens Implant Society, and replies were
      received from 59.2% prior to the cut-off date of February 15. Results were cross
      analyzed and compared with the data from American and British surveys.

PMID- 8145389
TI  - Aqueous flare and cell number in healthy eyes of Caucasians.
AB  - A prospective study was conducted using the laser flare-cell meter to determine
      aqueous flare intensity and cell counts in normal Caucasian eyes and to
      investigate factors which may have an effect on these measurements. The factors
      included age, iris color, pupillary size and pharmacologic dilation. We also
      compared the measurements of flare and cells in the right versus left eyes of the
      same individual to determine whether any difference exists between the aqueous
      protein concentration or cell count of two normal eyes. Ninety-two healthy
      Caucasians (184 eyes) whose ages ranged from 21 to 79 years were enrolled in the
      study. We found that there was no significant difference between the flare and
      cell measurements of the right and left eyes. The flare intensity range in this
      study population was between 1.3 and 7.6 photon count/ms. Flare increased
      significantly with aging (r = 0.562, P = 0.000). The baseline anterior chamber
      cell number did not vary significantly by age in the 3rd to 7th decades. Only in
      the 8th decade did a significant increase in cell number occur. No correlation
      between the undilated pupil size and the amount of flare or cells was found.
      After pharmacological pupillary dilation, anterior chamber flare significantly
      decreased and cell number significantly increased. The flare-cell meter is a
      sophisticated and sensitive instrument used to assess the condition of the blood
      aqueous barrier, but for accurate evaluations, the patient's age and the
      pharmacologic dilation of the pupil must be taken into consideration.

PMID- 8145390
TI  - Patients with asteroid hyalosis and visible floaters.
AB  - Four patients with asteroid hyalosis who complained of seeing multiple spherical
      floaters were examined. Except for multiple brilliant particles in the gelatinous
      vitreous, no abnormalities were found by ophthalmoscopic examination. Asteroid
      bodies usually cause no visual symptoms in most patients. Therefore it is unusual
      that our patients with asteroid hyalosis perceived floaters. We concluded that it
      was because there had been no vitreous detachment so that the asteroid particles
      were located close enough to the retina to be perceived as floaters.

PMID- 8145391
TI  - Indocyanine green video-angiographic findings in Harada's disease.
AB  - Indocyanine green (ICG) video-angiography was performed in 8 cases of Harada's
      disease and the findings were compared with those of fluorescein angiography. ICG
      video-angiography was confirmed to be far superior to fluorescein angiography in
      evaluating the choroidal vasculature seen in Harada's disease. Before retinal
      detachment appeared, the early phase of ICG video-angiography revealed decreased
      numbers of large fluorescent choroidal vessels as well as patchy areas of
      hypofluorescence. When retinal detachment became prominent, the large fluorescent
      choroidal vessels seen on ICG video-angiography were significantly fewer in
      number and patchy areas of hypofluorescence could be seen in the early phase. In
      the late phase, pooling of dye leakage became prominent. When retinal detachment
      subsided, the number of fluorescent choroidal vessels had increased. These
      results suggest that the decreased number of large fluorescent choroidal vessels
      seen in the early phase of ICG video-angiography indicate circulatory disturbance
      of the choroidal vessels, the degree of which may correspond to the exudative
      retinal detachment characteristic of Harada's disease. Patchy areas of
      hypofluorescence indicated blockage due to multiple choroidal granulomas and
      Dalen-Fuchs nodules.

PMID- 8145392
TI  - Case-control study of senile cataract in Japan: a preliminary report.
AB  - A hospital-based case-control study of senile cataract was conducted in Japan
      from 1988 to 1990. Two hundred and twelve patients with senile cataract and 212
      control subjects with the same age-sex distribution were interviewed and given an
      ophthalmological examination. Both groups were randomly selected outpatients from
      9 hospitals. Associations between senile cataract and four groups of variables,
      factors regarded as risks, life style habits, general aging indices or other
      factors were analyzed, and the data was subjected to statistical analysis. An
      increased risk of cataract was found in males who were presently spending 7 hours
      or more outside daily (Odds ratio = 5.07) and in females with 4 or fewer
      remaining teeth (Odds ratio = 2.03). The findings from this study suggest that
      there may be a sex-related host sensitivity or life style which is predisposing
      to the development of senile cataract.

PMID- 8145393
TI  - Various fundus manifestations in a Japanese family with Best's vitelliform
      macular dystrophy.
AB  - Recently we examined 7 members in one Japanese family with Best's vitelliform
      macular dystrophy. Five family members in three generations had abnormal electro
      oculographic (light peak/dark trough ratio) and normal electroretinographic
      responses, but their fundus manifestations varied. The proband (a girl) had
      yellowish macular lesions in both eyes and a neovascular membrane and subretinal
      hemorrhage in the left macula. The proband's grandfather had mottled macular
      lesions bilaterally and a mottled extramacular lesion in the left eye. The
      proband's father had yellowish macular lesions in both eyes and an extramacular
      lesion in the right eye. The proband's sister had ophthalmoscopically normal
      fundi. The proband's brother had yellowish macular lesions bilaterally. We
      believe that finding a variety of fundus manifestations of Best's vitelliform
      macular dystrophy in one family, as reported in this study, may be uncommon.

PMID- 8145394
TI  - Initial rapid decrease in visual acuity in siblings with Stargardt's disease.
AB  - Two siblings with Stargardt's disease who had an initial rapid decrease in visual
      acuity were reported. The 8-year-old boy and his 5-year-old sister experienced a
      bilateral visual decrease within a period of 3 months. Their parents had a
      consanguineous relationship. Macular changes and blocked choroidal fluorescence
      were noted bilaterally in both children. Normal color vision, normal or subnormal
      electroretinographic findings, and subnormal electro-oculographic responses were
      found. Stargardt's disease should be included in the list of conditions showing
      rapid decrease in visual acuity.

PMID- 8145395
TI  - Subclassification of preproliferative diabetic retinopathy.
AB  - One hundred and fifty-five eyes (106 cases) affected by preproliferative diabetic
      retinopathy were divided into three subgroups according to the severity of
      retinopathy and were followed for one year. The criteria for and numbers of eyes
      in each group were as follows: 1) mild type with soft exudates and without
      apparent nonperfused areas on fluorescein angiography (39 eyes), 2) moderate type
      with soft exudates and demonstrable nonperfused areas (103 eyes), 3) severe type
      with soft exudates, nonperfused areas and venous beading (13 eyes). The
      proportion undergoing photocoagulation was 23% in the mild type, 81% in the
      moderate type and 100% in the severe type. None of the mild type eyes underwent
      photocoagulation unless they advanced to a more severe type. Nine of the mild
      type eyes which progressed to moderate type during the follow-up period underwent
      focal photocoagulation. Panretinal photocoagulation was performed in 29% of
      moderate type eyes and 77% of severe type eyes. The courses of these three
      subgroups were analyzed after one year of follow-up. The proportion developing
      proliferative retinopathy was 0% in the mild type, 18% in the moderate type and
      46% in the severe type. Based on the above results, it was concluded that the
      subclassification we proposed in this paper can be applied to the management of
      patients with preproliferative diabetic retinopathy.

PMID- 8145396
TI  - Orbital rhabdomyosarcoma: a twenty-year survey in Turkey.
AB  - Orbital rhabdomyosarcoma is the most frequently encountered primary malignant
      orbital tumor in children. Between 1970 and 1991, 68 primary orbital
      rhabdomyosarcoma cases were diagnosed and treated in our clinic. Mean age at the
      time of diagnosis was 8.8 years. Seventy-two percent of the cases were of the
      embryonal type while 14% had alveolar and 14% had botryoid tumors. Following
      tissue diagnosis by anterior orbitotomy, radiotherapy and multimodal chemotherapy
      were instituted promptly. Subtotal exenteration was used in massive orbital
      involvement and total exenteration in recurrences. Using the Kaplan-Meier method
      of analysis, the survival rate was 84% at three years and 80% at five years.
      While morbidity due to the disease itself and treatment complications may still
      be a problem, the survival rates achieved in the long term are promising.

PMID- 8145397
TI  - Diagnostic impression cytology for herpes simplex keratitis.
AB  - Herpes simplex virus (HSV) antigens in corneal or conjunctival epithelial lesions
      were detected by impression cytology. Specimens were obtained using a
      nitrocellulose membrane and were stained by the peroxidase-antiperoxidase method.
      HSV antigens were demonstrated in 30 of 32 patients with herpes simplex keratitis
      or conjunctivitis. Impression specimens of dendritic or stellate keratitis
      lesions exhibited precise replicas of corneal lesions with numerous antigen
      positive cells. HSV antigens were also detectable in some of the minute stellate
      and/or punctate epithelial keratitis lesions even during the course of antiviral
      treatment. Impression cytology is noninvasive and useful for a rapid etiological
      diagnosis of herpetic epithelial lesions.

PMID- 8145398
TI  - Double-masked comparative study of UF-021 and timolol ophthalmic solutions in
      patients with primary open-angle glaucoma or ocular hypertension.
AB  - A double-masked comparative clinical study of UF-021 (Rescula), a unique
      prostaglandin-related compound, was carried out at 18 centers with timolol
      maleate 0.5% ophthalmic solution as an active reference drug. After a wash-out
      period, UF-021 (0.12%) or timolol (0.5%) was given topically twice a day for 12
      weeks to 158 patients with primary open-angle glaucoma or ocular hypertension, in
      a randomized double-masked manner. Both groups showed a significant reduction in
      intraocular pressure from the second week to the end of the study. In overall
      improvement rating, 91.4% of the cases (64/70) in the UF-021 group and 88.3%
      (68/77) in the timolol group were judged to be "Extremely improved" or
      "Improved". Five and 4 cases reported having side effects in the UF-021 and
      timolol groups, respectively, but none of the cases required any change or
      discontinuation of treatment. While UF-021 did not affect blood pressure, both
      systolic and diastolic blood pressures in the timolol group were significantly
      decreased. These results suggest that UF-021 (0.12%) has the potential to lower
      intraocular pressure equivalent to timolol (0.5%), while having no effect on
      cardiovascular functions.

PMID- 8145399
TI  - Intracellular Cl- activity in rabbit proximal convoluted tubule perfused in
      vitro: regulation by sodium and effects of anion transport inhibitors.
AB  - The mechanism of Cl transport was studied in rabbit proximal convoluted tubules
      (PCT) perfused in vitro by measuring intracellular Cl activity (AiCl) with double
      barreled Cl-selective microelectrodes. Luminal Cl removed decreased AiCl from
      27.4 to 23.7 mM (by 3.7 mM), whereas bath Cl removal decreased AiCl from 27.4 to
      12.3 mM (by 13.1 mM). Therefore, the basolateral membrane Cl transport was
      stronger determinant of AiCl. Basolateral SITS (1 mM) decreased AiCl from 33.9 to
      18.7 mM (by 15.2 mM) while 1 mM bath furosemide did not change AiCl. Bath SITS
      mostly abolished the difference between AiCl change by luminal Cl removal and
      that by bath Cl removal. On the other hand, DIDS (0.5 mM) or furosemide (0.1 mM)
      in the lumen barely changed AiCl. Removal of luminal Na decreased AiCl from 34.6
      to 25.4 mM (by 9.2 mM). After luminal Na removal, subsequent bath Na removal
      increased AiCl initially, and then decreased to a steady-state AiCl (30.3 mM)
      which was close to equilibrium Cl distribution across the basolateral membrane
      (28.4 mM). It is concluded that AiCl of PCT is regulated more strongly by
      basolateral Cl transport, and that Na-dependent Cl transport mechanisms are
      present at each cell membrane of PCT epithelium.

PMID- 8145400
TI  - Destabilization of the respiratory control by hypoxic ventilatory depressions: a
      model analysis.
AB  - Hypoxia induces unstable breathing such as Cheyne-Stokes breathing primarily
      through the increase in the peripheral chemoreceptor gain to CO2. Another
      consequence of hypoxia may be the direct depression of the respiratory center
      known as hypoxic ventilatory depression (HVD). The present study was undertaken
      to predict the effect of HVD on the generation of unstable breathing during
      hypoxia by way of a computer simulation. To represent HVD, the present
      respiratory control model includes the control of cerebral blood flow and a
      mechanism which reduces ventilation in proportion to the brain tissue PO2.
      Analyses conducted both in the frequency domain and the time domain demonstrated
      that incorporating the HVD mechanisms into the model considerably increased the
      open-loop gain and thereby destabilized the respiratory control system. Increase
      in the peripheral CO2 gain due to relative hypoxia (caused by ventilatory
      depression) accounted for only half of the increase in the overall loop gain
      found in the presence of HVD. Considerable portion of the increase in the open
      loop gain could be explained by the relative hypercapnia due to ventilatory
      depression.

PMID- 8145401
TI  - Oxygen consumption for constant work is minimal at lowest working contractility
      in normal dog hearts.
AB  - We tested whether minimal myocardial oxygen consumption (MVO2) for a given
      external work would exist in the middle of a normal contractility range as
      previously predicted theoretically. The left ventricle of the excised cross
      circulated dog heart preparation was connected to a volume servo pump. Myocardial
      contractility in terms of ventricular end-systolic elastance (Emax) was gradually
      increased from control 8.9 +/- 3.4 (mean +/- SD) to 30.0 mmHg/(ml/100 g) by
      epinephrine and decreased to 1.8 mmHg/(ml/100 g) by propranolol while heart rate,
      end-systolic pressure and stroke work were kept constant. MVO2 was determined as
      the product of total coronary flow and coronary arteriovenous oxygen content
      difference in each contractile state. We plotted MVO2 values against E(max)
      values in each heart. The MVO2-E(max) relation for a constant cardiac work showed
      that MVO2 was minimal at the low end of the covered E(max) range. We conclude
      that minimal MVO2 for a given cardiac work is generally obtained at the lowest
      working contractility in normal dog hearts. This conclusion might pose some
      problems in the previous theoretical prediction as to the contractility that
      achieves the minimal MVO2 in a given external work.

PMID- 8145402
TI  - Measurement of transverse stiffness during contraction in frog skeletal muscle
      using scanning laser acoustic microscope.
AB  - The change in the transverse propagation velocity was measured by the scanning
      laser acoustic microscope (SLAM) during contraction in living frog skeletal
      muscles. The images of the interferogram were processed by image-analyzer and the
      propagation velocity was calculated from the shift of the interference lines at
      rest and during contraction. In all the measurements, the velocities during
      contraction were clearly slower than at rest and this fact indicates that the
      transverse stiffness decreased during contraction. After stimulation, the
      beginning of the decrease in the propagation velocity preceded that of the
      increase in force by 30-40 ms, suggesting that the decrease in the transverse
      stiffness reflects the molecular mechanism of force development in muscular
      contraction.

PMID- 8145403
TI  - Relationship between body core and peripheral temperatures at the onset of
      thermoregulatory responses in rats.
AB  - The relationships between body core temperature and environmental temperature
      (T(a)) at the onset of tail skin vasodilation, thermally-induced salivary
      secretion and cold-induced thermogenesis were examined in rats. Hypothalamic
      temperature (Thy) was measured as an index of body core temperature. Internal
      body heating and cooling were made using an intravenous thermode chronically
      implanted in the inferior vena cava at various T(a)s. External heating and
      cooling were made by changing T(a) at a constant rate, while Thy was controlled
      at constant levels with the thermode. Internal heating induced tail skin
      vasodilation but not thermally-induced salivary secretion, and internal cooling
      induced cold-induced thermogenesis. External warming caused tail skin
      vasodilation and thermally-induced salivary secretion, but external cooling
      failed to induce cold-induced thermogenesis. There were significant correlations
      between Thy and T(a) at the onset of tail skin vasodilation, thermally-induced
      salivary secretion and cold-induced thermogenesis. When T(a) was taken as an
      indicator of thermal input from the skin, the ratios of the potency of inputs
      from the body core and skin were estimated to be between 8:1 and 6:1 at the onset
      of tail skin vasodilation, 8:1 at the onset of thermally-induced salivary
      secretion, and 5:1 for the control of cold-induced thermogenesis. These results
      suggest that, in rats, the contribution of thermal input from the skin to the
      onset of thermoregulatory responses is relatively small.

PMID- 8145404
TI  - Inspiratory prolongation by vagal afferents from pulmonary mechanoreceptors in
      rabbits.
AB  - Graded inflation and deflation pressures were transiently applied to the airway,
      and the effects on the inspiratory (TI) and expiratory (TE) durations were
      studied in twelve Japanese white rabbits tracheotomized and anesthetized with
      urethane and chloralose. Without vagal cooling, lung inflation prolonged TE,
      whereas changes in TI were small and inconsistent. The bilateral vagus nerves
      were cooled to 7 degrees C to block myelinated fibers, and to study the effects
      of C-fiber afferents. During vagal cooling to 7 degrees C, inflation dose
      dependently prolonged the first TI with no consistent change in TE. Without vagal
      cooling, lung deflation shortened TE of the first and succeeding breaths, and
      prolonged TI of the first breath to manifest apneusis. Deflation applied at the
      vagal temperature of 7 degrees C induced slight shortening of TI and TE in 6 of
      the 12 rabbits. All these changes were blocked when the vagus nerves were cooled
      to 1 degree C. The results may indicate that vagal afferents from irritant
      receptors shorten TE, and C-fiber afferents prolong TI. High irritant afferent
      activity may markedly shorten TE, causing tidal inspiratory activities to merge
      and manifest apneusis. Capsaicin, which is suggested to be a "selective"
      stimulant of C-fiber receptors was injected into the right atrium in 4 of the 12
      rabbits. The chief changes were TE shortening without vagal cooling, and TI
      prolongation during cooling to 7 degrees C. This suggests that capsaicin injected
      into the pulmonary circulation stimulates both the irritant and C-fiber receptors
      and the C-fiber afferents may prolong TI even when stimulated chemically.

PMID- 8145405
TI  - Alteration of nyctohemeral changes in body core temperature by repeated cold
      exposure given at a fixed time daily in rats [corrected].
AB  - The effects of cold exposure for several hours at a fixed time once a day on
      nyctohemeral variations of hypothalamic temperature (Thy), heat balance, and
      feeding and locomotor activities were examined in rats. The cold-exposed group
      was subjected to an ambient temperature of 3 degrees C for about 5 h in the last
      half of the dark phase daily for 10 or more than 21 consecutive days, while the
      control rats were kept constant at 24 degrees C. The 10-d cold exposure had
      little effect on nyctohemeral changes in Thy and locomotor activity. However,
      after completing a 3- to 4-week cold exposure schedule, the levels of Thy, heat
      loss, heat production, and feeding and locomotor activities of the cold-exposed
      rats significantly decreased for 1-2 h during the period of the previous cold
      exposure time. These decreases lasted for at least 2 d after the end of the cold
      exposure schedule. These results suggest that the patterns of nyctohemeral
      changes in body core temperature and feeding and locomotor activities were
      altered after repeated cold exposure at a fixed time once a day in rats.

PMID- 8145407
TI  - Ethics committees.

PMID- 8145406
TI  - The role of intraabdominal pressure in venous blood drainage from the prostate
      into the vertebral vein system.
AB  - We investigated venous blood drainage from the prostate into the vertebral vein
      system by cineangiography in five mongrel dogs and measured intraabdominal
      pressure and venous blood pressure in the dog or human to study the role of
      intraabdominal pressure in the drainage. The averages of intraabdominal pressure
      and caudal vena caval pressure in the dog were 32.2 +/- 3.0 and 12.8 +/- 1.3
      mmHg, respectively, in the supine position, and 39.2 +/- 3.0 and 23.8 +/- 4.0
      mmHg, respectively, in the head-up tilt position, when the radiopaque medium
      injected into the dorsal penile vein appeared in the vertebral vein system.
      Intraabdominal pressure in the head-up tilt position was significantly higher
      than that in the supine position when the venous drainage into the vertebral
      veins happened. In eight continuous ambulatory peritoneal dialysis patients,
      intraabdominal pressure showed 8.1 +/- 2.4 mmHg in the supine position, 24.6 +/-
      4.3 mmHg in the sitting position, and 30.4 +/- 4.9 mmHg in the standing position
      at rest. During voluntary contraction of the abdominal muscles, the pressure was
      increased up to 50.6 +/- 21.6 mmHg in the supine position, 69.3 +/- 19.8 mmHg in
      the sitting position, and 73.8 +/- 19.8 mmHg in the standing position. These
      pressure values in the human were significantly higher than those observed at the
      time when the radiopaque medium appeared in the vertebral veins in both supine
      and head-up tilt positions in the canine. These results suggest that the increase
      of intraabdominal pressure causes inflow of prostatic venous blood into the
      vertebral veins via the inferior vena cava, common iliac vein, or internal iliac
      vein.

PMID- 8145408
TI  - A season for children.

PMID- 8145409
TI  - Meniere's disease.
AB  - Meniere's disease is one of the most common etiologies for dizziness in the
      United States. The mainstay of therapy for Meniere's is medical therapy.
      Symptomatic treatment is employed, but long-term prophylaxis is emphasized, with
      salt restriction and diuretic administration as needed. A prophylactic approach
      can prevent many attacks and ameliorate those that do occur. Patients with
      moderate to severe symptoms who fail medical therapy may be candidates for
      endolymphatic sac surgery, since this procedure is successful in a majority of
      patients and has low morbidity. Those patients in whom an endolymphatic shunt
      fails and who continue to have severe symptoms may undergo selective sectioning
      of the vestibular nerve, while patients with no residual hearing may be offered
      translabyrinthine nerve section.

PMID- 8145410
TI  - Pseudomonas osteomyelitis following puncture wounds of the foot.
AB  - The management of puncture wounds of the foot should include routine wound care,
      tetanus prophylaxis and warnings of what to look for and expect. Pseudomonas
      aeruginosa is the most commonly recovered organism in puncture wounds. Should
      symptoms develop, aggressive intravenous antibiotic treatment should be initiated
      if symptoms occur within seven days. Clinical presentation is characterized by
      minimal systemic symptoms, few laboratory abnormalities, and asymptomatic
      patients until the obvious presentation of osteomyelitis. After seven to 14 days,
      the would should be surgically treated and appropriate antibiotics administered.

PMID- 8145411
TI  - Coincidental metastatic intestinal neuroendocrine carcinoma and esophageal
      adenocarcinoma.

PMID- 8145413
TI  - [The BP level and its relation to the indices of physical development in 14-year
      old adolescents living in Ulan-Ude (based on the data from a single
      epidemiological study)].

PMID- 8145412
TI  - [The effect of the physical status of the neutrophil membranes on their
      functional metabolic activity in hypertension patients].
AB  - In 76 untreated patients with Stages I-II hypertensive disease, spectrophotometry
      with lipid specific pyrene fluorescence probe revealed higher microviscosity in
      the lipid phase of neutrophilic membranes, which was induced by elevated levels
      of cholesterol and enhanced activation of lipid peroxidation. This resulted in
      increased functional and metabolic neutrophilic activity which was determined by
      luminol-dependent zimozan-induced chemiluminescence of whole venous blood. The
      correlation coefficient between the microviscosity of membranes and the
      chemiluminescence of neutrophils is 0.82 (p).

PMID- 8145414
TI  - [Ought plasmapheresis be used in the treatment of hypertension patients?].
AB  - The paper discusses the results of using plasmapheresis in the multimodality
      treatment of 51 patients with Stage II hypertensive disease. It has been found
      that the application of plasmapheresis results in the patient's clinical
      improvement as attenuation of headache and giddiness, cessation of cardialgia and
      better general condition. After plasmapheresis treatment, a dosage of
      antihypertensive agents could be reduced in most patients. The findings suggest
      that plasmapheresis opens up new fields of use in the treatment of hypertensives,
      exerting a substantial effect on immunological and hemorheological parameters and
      making the baseline changed hemodynamic parameters normal.

PMID- 8145415
TI  - [The immunological aspects of primary chronic septic endocarditis in acquired
      heart defects. The treatment approaches].
AB  - A total of 266 patients with degree I primary chronic septic endocarditis
      concurrent with acquired heart disease and 101 apparently healthy subjects were
      examined. The patients were found to have scarce T helper cells and higher levels
      of T suppressors (quite the reverse in some patients), decreased proliferative
      responses of T and B cells and normal levels of circulating immune complexes. It
      was conceived that there was a block in the synthesis of specific antibodies and
      a decrease in their affinity. It was proposed that cytokine (enzyme) genes
      (initiators or repressors) should be exposed at intervals as immunomodulating
      therapy of immune diseases, as well as in some hereditary diseases.

PMID- 8145416
TI  - [Congenital heart defects with a left-to-right shunt: capillarotrophic failure of
      the microcirculatory system].
AB  - Microbiological and morphological methods were used to study abnormalities in the
      greater microcirculation in acyanotic heart disease. The bulbar conjunctiva
      (patients), greater omentum and cardiac serous membranes (autopsy material) were
      used as test objects. The most marked changes were revealed in the metabolic link
      of the microcirculatory system. They were characterized by progressive reduction
      in intrinsic capillaries and an increase in the modulus of microcirculation of
      microvessels (capillaries) of the great (exchange-shunting) type. The
      alternations in the structure of the microcirculatory system were accompanied by
      centralization of tissue blood flow and its decreased metabolic efficiency, which
      were clinically manifested by tissue capillary trophic tissue failure with the
      occurrence of a number of severe common symptoms of the disease and various organ
      lesions in children. Analyzing the results of the study enabled the author to be
      the first to reveal in the above cardiac pathology specific tissue blood
      circulatory disorders which are interpreted as a phenomenon of centralized
      microhemodynamics. The important results of the study is also the
      morphofunctional rationale for the concept "capillary trophic incompetence".

PMID- 8145417
TI  - [The echocardiographic assessment of heart function in the early postoperative
      period in patients following the radical correction of tetralogy of Fallot].

PMID- 8145418
TI  - [Blood flow in the left pulmonary veins and the regional nonuniformity of the
      left ventricular myocardium: an ultrasonic Doppler study].
AB  - The paper elucidates the nature of systolic peak cleavage in pulmonary venous
      blood flow into the major (J) and auxiliary (J') ones. A hypothesis has been
      forwarded, according to which the occurrence of the peak J' is associated with
      the kinetics of left ventricular walls and mitral ring due to regional left
      ventricular myocardial heterogeneity. The paper also provides indirect evidence
      for this hypothesis, which has been obtained by Doppler ultrasonic study of 13
      healthy individuals and 34 patients with various cardiovascular diseases. It has
      been found that in most cases the cleavage of the peak J was observed in patients
      with pronounced regional left ventricular myocardial heterogeneity (postinfarct
      aneurysm, dilated cardiomyopathy, Wolff-Parkinson-White syndrome, etc.).

PMID- 8145419
TI  - [Disorders of the central and intrapulmonary hemodynamics as an index of the
      degree of severity in myocarditis patients].
AB  - Central and intrapulmonary hemodynamic parameters were examined by direct and
      indirect methods in 46 patients with myocarditis (25 females and 21 males), which
      revealed diminished myocardial contractility, which was followed by a regular and
      significant pulmonary blood pressure and a reduction in the elastic properties of
      the pulmonary-arteriolar bed. Central and intrapulmonary hemodynamic changes are
      mostly associated with the development of hypodynamia and more rarely with that
      of the phase hemodynamic syndrome and more rarely with the volume overloading
      syndrome.

PMID- 8145420
TI  - [The diagnostically significant indices of the corrected axial ECG system in the
      differentiation of ischemic heart disease and dilated cardiomyopathy].
AB  - The common uniformity of electrocardiographic changes in coronary heart disease
      (CHD) and dilated cardiomyopathy (DCMP) in the lead XII, namely low QRS complex
      voltage, T-wave inversion, cardiac arrhythmias, atrioventricular and
      intraventricular conduction disturbances, served as the basis for searching for
      individual or combined lesion signs quantitatively diagnostically significant for
      CHD and DCMP. For this purpose, 217 patients were examined. Out of them 83 were
      included into a group of healthy persons and 134 were patients who were divided
      into two groups: 60 with chronic CHD and 74 with DCMP. The authors identified a
      complex of diagnostically significant ECG parameters of the McPhi-Parungao
      system. SX > 4 mm, SZ > 12 mm, RX + SZ > 27 mm, sigma RXYZ + sigma SXYZ > 45 mm,
      sigma RXYZ/sigma SXYZ < 1.5, which permits differentiation of DCMP and CHD in
      case of lowered QRS voltage on ECG-12.

PMID- 8145421
TI  - [Decreased tonus of the epicardial coronary arteries in patients with dilated
      cardiomyopathy].
AB  - The tone of coronary artery (CA) was evaluated in 26 patients with dilated
      cardiomyopathy (DCMP) and 20 patients with atypical chest pain, intact CA, and
      normal left ventricular contractility served as controls. All the patients
      underwent selective polyviewed coronarography, left and right ventriculography.
      The configurations of the great CA were examined by a computer which calculated
      their mean diameter in diastole (Dd) and systole (Ds), their difference (d) and
      the elasticity index (EI) by the formula: d/Dsx 100%. Twelve patients with DCMP
      and 10 control patients had repeated left coronary contrasting after
      intracoronary injection of nitroglycerin, 150 mg, they authors calculated the
      baseline Dd (Dd1), Dd after nitroglycerin (Dd2), the degree of nitroglycerin
      induced CA dilation. Ds was found to be greater than Dd in the two groups. The
      mean CA diameter was significantly more in DCMP patients who had lower D and EI.
      Intracoronary nitroglycerin injection caused a less marked increase ion the Dd of
      the anterior descending CA in DCMP patients. Thus, the computer-aided analysis of
      coronarograms and nitroglycerin test allowed one to quantitatively determined the
      decreases in CA in DCMP.

PMID- 8145422
TI  - [The myocardial blood supply in chronic alcoholism patients studied by myocardial
      scintigraphy with 201Tl].
AB  - To study myocardial perfusion, 201Tl myocardial scintigraphy was used to examine
      25 patients with chronic alcoholism and alcoholic damage to the heart. 201Tl
      myocardial scintigraphy was performed at rest and repeatedly 3-7 days later by
      using the bicycle ergometer exercise test. The total 201Tl uptake at rest was 2.3
      +/- 0.2%. The resting scintigrams of the patients showed a profound irregularity
      of 201Tl distribution and a diffuse decrease in its washout. The increment of
      201Tl uptake in response to exercise was 20.6%. Exercise scintigrams displayed
      steady perfusion defects mainly of anteroseptal site. There was an improvement of
      tracer washout in the exercise test as compared at rest. Thus, 201Tl myocardial
      scintigraphy allows perfusion disturbances to be detected in patients with
      alcoholic damage to the heart. Myocardial scintigraphy performed at the peak of
      exercise records a decreased increment of 201Tl extraction, suggesting a lower
      perfusion reserve in patients with alcoholic heart damage.

PMID- 8145423
TI  - [Subclinical hypothyroidism in patients with ischemic heart disease].
AB  - A total of 187 patients with coronary heart disease (CHD) were examined. Out of
      them 60% were found as having subclinical hypothyroidism. The serum levels of T3
      were significantly lower, particularly in arrhythmic CHD, the level of T4 was
      normal and even increased, thus making the concentrations of TTG normal, i.e. the
      T3-low-syndrome was detected. Hypothyroidism in CHD patients decreased tissue
      oxygen consumption, by reducing the incidence of acute myocardial infarction,
      heart failure, the atherosclerotic process becoming disseminated and progressive.
      Cordarone therapy was found to promote the progression of T3-hypothyroidism, i.e.
      in CHD patients with suspected hypothyroidism, the drugs inhibiting the thyroidal
      function should not be used. T3-Hypothyroidism should be corrected with adequate
      doses of triiodothyronine in CHD patients. The use of thyroxine is ineffective as
      the conversion of T4 to T3 is impaired in the body.

PMID- 8145424
TI  - [An evaluation of the hypolipidemic effects of lovastatin in primary
      hypercholesterolemia. A multicenter study].
AB  - In the multicenter trial, the hypolipidemic efficacy and adverse event profile of
      lovastatin were estimated in 294 patients with primary hypercholesterolemia. The
      mean baseline (on placebo) lipid and lipoprotein values were: total serum
      cholesterol (TC) 313 mg/dl, triglycerides (TG) 168 mg/dl, low density lipoprotein
      cholesterol (LDL-C) 235 mg/dl, high density lipoprotein cholesterol (HDL-C) 44.9
      mg/dl. Lovastatin was begun with 20 mg/day, the dose being doubled after 4 and 8
      weeks if the target reduction of TC < 200 mg/dl was not reached at those moments.
      At the end of the treatment the mean TC decreased by 29.5% (p) as compared with
      the baseline level, TG by 14% (p). The normal target level of TC was reached in
      106 patients (36%), the borderline levels (200-240 mg/dl) in 123 (42%), high TC
      (240 mg/dl) remained in 65 patients (22%). LDL-C decreased by 38% (p), HDL-C
      increased by 7.8% (p), whereas LDL-C/HDL-C ratio decreased by 40% (p). The
      treatment was well tolerated by patients: mild clinical side effects were noticed
      in 2.7% of patients and asymptomatic transient deviations of laboratory tests in
      8.2%. The authors conclude about high hypolipidemic efficacy and low adverse
      event profile of lovastatin in patients with primary hypercholesterolemia.

PMID- 8145425
TI  - [The prevention of paroxysmal atrial fibrillation complicating the course of sick
      sinus syndrome].

PMID- 8145426
TI  - [The molecular cellular aspects in predicting the course of an acute myocardial
      infarct].
AB  - Ultra-high-frequency dielectrometry was used to determine the dielectric
      permeability of erythrocyte suspension cell membranes in 48 patients with acute
      myocardial infarction who were given agonists, antagonists, and modulators of the
      adenylate cyclase system. The study showed that the functional status of
      erythrocyte membranes changed correlating with the clinical course of the
      disease. Changes in this status were followed by complications of improvement. It
      was evidenced that the trend of a pathological process in coronary stress was
      associated with the functional status of erythrocyte membranes. Ultra-high
      frequency dielectrometry is a sensitive method for evaluating the status of
      patients with myocardial infarction, controls the natural history of the diseases
      at the molecular level and to predict the development of complications.

PMID- 8145427
TI  - [The characteristics of neuroendocrine regulatory disorders in acute myocardial
      infarct in relation to the severity of the course of the disease].
AB  - A total of 45 patients aged 35 to 73 years who had sustained acute myocardial
      infarction (MI) were studied in a special cardiological unit. On days 1, 5, 14,
      28 of hospital stay, each patient underwent measurements of cortisol, insulin, T3
      and T4 and calculations of the mathematical clinic severity index after G.I.
      Marchuk et al. In acute MI, there were elevated plasma levels of cortisol
      depending on the MI severity with a small repeated peak of its increase on day 14
      and its subsequent decrease, except deaths. In severe acute MI there were
      impairments of reciprocal cortisol/insulin ratios. This was particularly
      pronounced in patients with lethal outcomes. By the end of hospital
      rehabilitation, patients with acute MI displayed lower levels of thyroidal
      hormones. The maximum decrease in T3 and T4 was found in patients with lethal
      outcomes. There was a direct correlation between the mathematical clinical
      severity index of the natural history of acute MI and the levels of cortisole
      triidothyronine at the hospital stage of observation. In the course of the study
      it was found that the Marchuk clinical severity index serves as an informative
      severity index of MI course whose determination in its acute period allows one to
      predict the course of acute MI and to choose a differential therapy of and to
      make a diagnosis of possible complications.

PMID- 8145428
TI  - [The characteristics of arterial hypertension and the changes in thrombocyte
      vascular hemostasis in shepherds migrating in the mountains].

PMID- 8145429
TI  - [Enduracin--a nicotinic acid preparation in the treatment of
      hypercholesterolemia].

PMID- 8145430
TI  - [The effect of monotherapy with nifedipine and hydrochlorothiazide on the
      psychological characteristics and quality of life of hypertension patients].
AB  - The study comprised 25 males with Stages I-II hypertensive disease whose age was
      35 to 60 years and diastolic blood pressure was 96-114 mm Hg. After 4-week
      administration of placebo, two groups of treatment were randomized: (1)
      nifedipine (corinfar), 15-80 mg daily, and (2) hydrochlorothiazide (triampur), 25
      100 mg daily, for 12 weeks with subsequent crossover: between therapy course, the
      patients received placebo during 4 weeks. The psychological examination was
      performed before the patients' inclusion into the study, at the end of placebo
      use, 4 and 12 weeks after monotherapy with one of the active drug, by using the
      "Lifestyle" questionnaire, SMOL and HPPQ. The study showed that a course of
      therapy with the calcium antagonist nifedipine produced a beneficial effect on
      the mental status and lifestyle in patients with hypertensive disease, by
      promoting the improvement of relations between the patients and all those
      present. Hydrochlorothiazide monotherapy deteriorated the lifestyle in patients
      by restricting smoking and sexual life and enhanced neurotization in patients,
      especially in subjects who had no benefits. It has been ascertained that the
      efficacy of antihypertensive therapy depends on the baseline mental status of
      hypertensives: higher neurotization may be regarded as a predictor of
      inefficiency of treatment.

PMID- 8145431
TI  - [The effect of obzidan and visken on the regulation of the lymphocyte beta 2
      adrenoreceptor adenylate cyclase system during physical loading in hypertension
      patients].

PMID- 8145432
TI  - [The interrelationship of left ventricular dyskinesia and silent myocardial
      ischemia in patients with stable stenocardia].
AB  - A total of 40 patients with Functional Class III-IV stable angina pectoris were
      examined. Silent myocardial ischemia was detected in 87.5% of patients by using
      24-hour Holter monitoring. A statistically significantly greater amplitude and
      longer duration of pain episodes were observed. The patients underwent exercise
      echocardiography. Functional exercise was performed by frequent-increasing
      transesophageal cardiac pacing. The index of local myocardial contractility
      disturbances was assessed and calculated as the product sum of the number of
      diseases segments by the rating coefficient: hypokinesia, 1 score, akinesia, 2
      scores, and dyskinesia, 3 scores. There was a statistically higher segmental
      asynchronism in patients having a silent myocardial ischemic episode of more than
      15 min. The index of local contractility disturbance in this group of patients
      was 7.9 +/- 3.2 units. There was a relationship between the duration of silent
      myocardial ischemia and the presence of heart failure. It was concluded that the
      duration of silent myocardial ischemia might be used as an additional criteria
      for assessing the severity, prognosis and adequacy of therapy in patients with
      stable angina on effort.

PMID- 8145433
TI  - [The role of physical training on the bicycle ergometer with an optimal pedalling
      rate in enhancing the efficacy of the sanatorium rehabilitation of patients who
      have had a myocardial infarct].
AB  - The impact of physical training on a bicycle treadmill was examined in 171
      patients with prior myocardial infarction by using individual pedalling rates at
      a sanatorium stage. During sanatorium rehabilitation, the proposed bicycle
      training allowed the authors to obtain the best clinical effects, more pronounced
      positive ECG dynamics, improved cardiac function with a simultaneous decrease in
      peripheral resistance, i.e. the economization and optimization of circulatory
      performance and considerably higher exercise tolerance. The positive effect of
      physical training with the optimum pedalling rate in patients with myocardial
      infarction at a sanatorium rehabilitative stage retained within 6 months and this
      was followed by a reduction in the number of anginal episodes, lower temporary
      disability and hospitalizations by thrice, restoration of the working capacity of
      a greater number (by 1.5 times) of patients than other patient groups.

PMID- 8145434
TI  - [The significance of a lesion of the subvalvular structures in mitral valve
      prosthesis: experience in using the 2-disk low-profile mechanical valve].

PMID- 8145435
TI  - [The diagnosis of false aneurysms of the proximal anastomoses after aortofemoral
      reconstructive operations].
AB  - The paper deals with the diagnostic aspects of false aneurysms of proximal
      anastomosis of prostheses with the aorta on the basis of examination of 9
      patients aged 3-65 years after aortofemoral reconstructive operations. The
      periods of the occurrence of false aneurysms were 2 weeks to 6 years. The causes
      of anastomosis aneurysms: infection in 3 patients, endarterectomy from the aorta
      at the site of applied anastomosis in 1 patient, progressive underlying disease
      in 2 and ill-grade suturing material (silk). The cause of the disease could not
      be established in 2 patients. The authors provide strong evidence for a high
      informative value of various examinations, including ultrasound echo scanning,
      computer tomography, radioopaque aortography. They also emphasize a great
      practical value of using the algorithm of microbial analysis of blood, urine, and
      tissue of false aneurysm for confirming its infections.

PMID- 8145436
TI  - [The value of digital-analog Holter monitoring systems in the noninvasive
      diagnosis of heart rhythm disorders].
AB  - By using the Custo Mega ECG monitoring system as an example, the value and
      efficiency of digital analog Holter monitoring systems in the non-invasive
      diagnosis of cardiac arrhythmias have been analyzed. The findings suggest that
      the Holter monitoring system produces high reliability, sensitivity (80.8-100%),
      and specificity (70.9-100%) in analyzing arrhythmic phenomena on ECG as compared
      to other Holter monitoring systems and electronic pacemakers.

PMID- 8145437
TI  - [Late ventricular potentials and intracardiac electrophysiological study].

PMID- 8145438
TI  - [The motion characteristics of the interventricular septum and their effect on
      cardiac hemodynamics in patients with an implanted pacer].
AB  - The paper presents echocardiographic findings of 91 patients with implantable
      pacemaker. Ventricular septal motion was found to be abnormal in 59 out of 65
      patients with endocardial stimulation. Moreover, they had early systolic motion
      and paradoxal septal contraction. Three types of abnormal septal motion were
      identified. In these patients, ECG recorded a picture of left bundle branch
      block. With myocardial stimulation, ventricular septal motion was normal. In
      abnormal septal motion, left ventricular ejection fraction was much lower than
      that in normal septal motion. Endocardial stimulation of the right ventricle is
      hemodynamically inferior to myocardial stimulation of the left ventricle.
      Abnormal ventricular septal motion associated with abnormal asynchronism in
      ventricular performance is one of the cause of the above phenomenon.

PMID- 8145439
TI  - [The prognosis of drug therapy efficacy in ventricular rhythm disorders by the
      level of intracellular Ca2+ in the lymphocytes of patients with ischemic heart
      disease].

PMID- 8145440
TI  - [Antioxidant therapy in the arrhythmic form of alcoholic heart damage].
AB  - The impact of antioxidative therapy with dibunol on the clinical course of an
      arrhythmic type of alcoholic damage was studied. A total of 20 patients with
      Stage II chronic alcoholism (mean age 38.1 +/- 1.9 years) and ventricular
      premature contraction were examined. The diagnosis of cardiac alcoholic damage
      was established after comprehensive studies. The effects of dibunol on the
      pattern of ventricular arrhythmias were tested by 24--hour Holter monitoring:
      control, on days 10 and 20 of therapy. The daily dosage of dibunol was 20 mg per
      kg body weight. The results of studies suggest that dibunol exerts a beneficial
      effect on the clinical course of the disease and the nature of ventricular
      arrhythmias by reducing the number of ventricular extrasystoles by 51.4%.

PMID- 8145441
TI  - [The effect of long-term probucol intake on the lipoprotein cholesterol content
      and glutathione peroxidase activity in the blood of patients with coronary
      arteriosclerosis and hyperlipidemia].
AB  - The authors present results of 6-month probucol (lipomal) therapy in patients
      with coronary heart disease concurrent with Types 2a and 2b hyperlipidemia. There
      were 22 and 23% increases in total cholesterol and low density lipoprotein
      cholesterol, respectively, whereas the levels of high density lipoprotein
      decreased and triglycerides remained unchanged. Having antioxidative properties,
      probucol enhanced the activity of the antioxidative enzyme glutathione peroxidase
      on an average twice, which should be borne in mind in evaluating the efficiency
      of treatment.

PMID- 8145442
TI  - [The possible effect of membrane-pathological processes on the atherogenicity of
      hypertension].
AB  - A total of 110 young males suffering from hypertensive disease (HD) were studied.
      Out of them 21 patients had concurrent HD. As HD progresses, there is an
      accumulation of free cholesterol in the lipid bilayer of erythrocytic membranes,
      which promotes the limitation of higher membrane permeability for calcium ions.
      The excessive accumulation of cholesterol also results in an additional decrease
      in Na+K+. ATPase activity and Ca(2+)-ATPase inhibition in the erythrocytic
      membranes in hypertensives, which produced atherogenic effects.

PMID- 8145443
TI  - [The antiatherosclerotic effect of verapamil in a cell culture of human aortic
      intima].
AB  - Verapamil was examined for effects on atherosclerotic manifestations in cultured
      human aortic intimal cells. Addition of verapamil in a concentration of 10(-6)
      10(-4) M to the cultured cells isolated from aortic atherosclerotic areas led to
      lower cellular lipids, suppressed cell proliferation and inhibited synthesis of
      collagen and cholesterol esters 24 hours after incubation. Verapamil also
      prevented atherogenic serum-induced accumulation of cholesterol in the cells
      isolated from normal aortic intimal areas. No decrease in cellular cholesterol
      levels was observed when the cells had been incubated with verapamil in the
      medium containing lipid-free serum. The findings suggest that the atherosclerotic
      effect of verapamil, which was seen in the experiments with animals, can be
      determined by the action of this drug on cellular processes.

PMID- 8145444
TI  - [A word about Irvine Page].
AB  - Doctor I. Page, a clinician, and his colleagues discovered angiotonin
      (angiotensin), isolated serotonin from blood. He described the interaction of the
      sympathetic and renin-angiotensin systems. Dr. I. Page was the first to use
      sodium nitroprusside in the clinical setting. He identified the juvenile
      hypertension syndrome Page's syndrome). He was the head of studies on diets of
      atherosclerotic patients. He forwarded a "mosaic" theory of the occurrence of
      systemic arterial hypertension.

PMID- 8145445
TI  - [Current trends in transluminal coronary angioplasty].

PMID- 8145446
TI  - [Antihypertensive preparations and the quality of life of hypertension patients].

PMID- 8145447
TI  - [The vasospastic component in the pathogenesis of unstable angina].
AB  - A comprehensive dynamic investigation revealed a group which included 31 (9.8%)
      patients with a response to the introduction of a probe-electrode during
      transesophageal pacing. It was characterized by ST-segment elevation and
      development of an anginal attack. The hemostatic parameters examined suggest that
      there is a special group among patients who have unstable angina with increasing
      vasospastic activity. The introduction of a probe-electrode may be considered to
      be a provocative test.

PMID- 8145448
TI  - [A case of the delayed diagnosis of a primary heart tumor].

PMID- 8145449
TI  - [The local vasoconstrictive reaction to acetylcholine in a patient with a
      virtually unaltered coronary artery].

PMID- 8145450
TI  - [Sex education and AIDS prevention].
AB  - The well-known deficiencies in sexual education prompt the author to present
      commendable education programmes by experienced sexual paedagogues. Emancipatory
      sexual education aims at preparing adolescents for adulthood. Most of the
      teenagers have other sexual anxieties than an HIV infection. These facts should
      be utilised for other methods of sexual education.

PMID- 8145451
TI  - [The pathogen spectrum of blood cultures of premature and newborn infants in a
      neonatal intensive care unit].
AB  - The bacterial spectrum of blood cultures in a neonatal intensive-care unit was
      retrospectively assessed in a two-year study. Analysis of positive blood cultures
      showed a dominance of gram-positive bacteria, especially of coagulase-negative
      staphylococci. The resistance of these germs points to vancomycin as the most
      effective antibiotic. B-streptococci, germs that are dreaded especially in
      neonatology, were not found in any of the cases. Positive blood cultures were
      mostly in correlation with clinical symptoms, less so to the leukocyte count
      and/or C-reactive protein levels. There was no case of death directly caused by
      sepsis.

PMID- 8145452
TI  - [Use of the Glasgow Coma Scale in pediatric craniocerebral trauma].
AB  - Over five years the applicability of a modified Glasgow Coma Scale was analysed
      in 38 children (mean age 7.2 +/- 3.8 years) with head and associated injuries
      (47.4%). The score was estimated after the accident and in the course of
      intensive therapy. At the beginning of the treatment on the intensive care unit,
      the cases were staged according to the severity of the head injuries (Glasgow
      Coma Scale: 4-8, 9-12 and 13-19 points). At the stage evaluated as between 4 and
      8 points, 50% of the patients died and the survivors were ventilated (11.7 +/-
      10.7 days) and intensively treated (45.7 +/- 31.5 days). All patients had had
      neurological damage. Additional injuries worsened the prognosis in the acute
      phase. 42.9% of the patients received intracranial pressure monitoring. In the
      patients between 9 and 12 points, the time of ventilation (3.7 +/- 2.9 days) and
      of intensive therapy (19.5 +/- 13.3 days) decreased. Over 13 points, all patients
      had a shorter duration of treatment (10.8 +/- 8.8 days) and a quick and good
      recovery. The Glasgow Coma Scale has the advantage of an examination with a
      quantitative analysis and resulting effective diagnostic and therapeutic
      measures. Even the inexperienced physician can use the Glasgow Coma Scale with
      success at the site of the accident.

PMID- 8145453
TI  - [15N liver function test in underweight infants, hypotrophic at birth].
AB  - Fifty-two infants were enrolled in the study: 23 hypotrophically born infants
      (birth weight < 5th percentile according to Kyank) with present body weights <
      3rd percentile according to Prader (group 1), 15 patients suffering from severe
      liver diseases (group 2), 14 patients without liver diseases (group 3). Usual
      serum parameters were estimated. Additionally, the hepatic detoxification
      capacities were measured using the non-invasive, non-radioactive [15N]methacetin
      urine test. 17 of the 23 infants of group 1 showed 15N elimination rates as low
      as in severe liver-diseased patients (group 2) whereas their serum parameters
      were in the normal range, as were those of group 3. The question remains whether
      intra-uterine malnutrition or postnatal effects, e.g., environmental conditions,
      caused the functional liver damage.

PMID- 8145454
TI  - [Ondine syndrome: presentation of pediatric aspects based on a case report].
AB  - The congenital central alveolar hypoventilation syndrome (Undine's syndrome, or
      Ondine's curse) is a rare disorder of central ventilation. In recent years a
      successful therapy has been found consisting of pacing of the diaphragm. Early
      diagnosis is therefore significant for preoperative management. In our paper, we
      present the clinical course of a female newborn with Ondine's curse. Conclusions
      for the further management by the paediatric staff are demonstrated.

PMID- 8145455
TI  - [Preventive vaccination (DPT, HiB, polio, MMR) in hepatitis B virus carrier
      status?].

PMID- 8145456
TI  - [Role of medicinal coal in primary management of poisoning].
AB  - Primary detoxication by ipecac-induced emesis or gastric lavage is incomplete. In
      mild to moderate childhood poisoning administration of activated charcoal alone
      without gastric emptying is often more effective, because it binds toxins
      promptly. In-vitro and in-vivo studies of many substances have shown good
      adsorption to activated charcoal (e.g. digitalis, beta-blocking agents,
      phenobarbitone, carbamazepine, theophylline). If in-vitro adsorption is moderate
      to poor, administration of activated charcoal might nevertheless prove clinically
      valuable by altering the severity of symptoms such as has been shown with
      acetaminophen, salicylates or organophosphate insecticide intoxications. Possible
      risks are shown and dosage regimens of activated charcoal are given alongside an
      evaluation of additional cathartics in the initial treatment of childhood
      poisonings. The role of repeated doses of activated charcoal as a method of
      secondary detoxication in comparison with hemoperfusion techniques and its
      significance in clinical routine is pointed out. General conclusion: In mild to
      moderate childhood poisoning early administration of activated charcoal alone
      after consultation of pediatrician and/or poison center specialists is an
      adequate therapy.

PMID- 8145457
TI  - [The use of xenogeneic splenic perfusates for treating suppurative-septic
      diseases].
AB  - It was shown in experiments on a model of fatal staphylococcal sepsis in 200 mice
      and 15 dogs that the perfusate of a pig's spleen obtained by perfusion of the
      isolated organ with a dextran solution (rheopolyglucin, polyglucin) is capable of
      preventing the animals' death. Intravenous infusion of 400-500 ml of a xenospleen
      perfusate at an interval of 1-3 days, which was included in the complex of
      postoperative treatment of 45 patients with destructive diseases of the abdominal
      organs complicated by peritonitis and sepsis, contributed to reduction of
      lethality and the terms of recovery. It is shown that the main effect, besides
      detoxification, is based on immunomodulation at the cost of biologically active
      substances produced by the cells of a xenospleen and contained in the perfusate.
      The best results were produced with the use of the perfusate of a xenospleen in
      the early periods after radical operation and thorough cleansing of the source of
      the infection.

PMID- 8145458
TI  - [The characteristics of suppurative wounds treated with xenogenic splenic
      homogenate].
AB  - The authors discuss the results of treatment of 60 patients with persistent
      purulent wounds by applications of pig spleen homogenate (30 patients) and by the
      commonly accepted method (30 patients). The cytologic and microbiological data
      studied during the course of the wound process in both groups are analysed. The
      terms of cleansing, regeneration, and epithelialization of the wound surface were
      analysed comparatively; they were found to be 1.5 times shorter in treatment with
      a homogenate of xenogeneic spleen. It was thus established that a pig spleen
      homogenate produces a good antiinflammatory and necrolytic effect and absorbs the
      detritus, microbes, and toxins.

PMID- 8145459
TI  - [Determination of antimicrobial activity of wound discharge for assessing wound
      healing].
AB  - The authors studied the dynamics of changes of antimicrobial activity of the
      wound discharge in 70 patients, aged from 18 to 83 years, who underwent
      operations for emergency diseases of the abdominal organs with postoperative
      suppuration of the wound. The study was conducted at the peak of suppuration, in
      the regeneration phase, and before closure of the wound with sutures. The
      antimicrobial activity of the wound discharge was found to be low at the peak of
      wound suppuration with marked necrotic changes of the tissues, as well as in poor
      granulations, and good in uncomplicated course of the wound process. Changes of
      antimicrobial activity of the wound discharge, both in uncomplicated and
      complicated course of the wound process, correlated with the clinical signs of
      healing. The obtained data make in possible to determine antimicrobial activity
      of the wound discharge for evaluation of healing, prognostication of bacterial
      complications in the wound, and control over the efficacy of the treatment.

PMID- 8145460
TI  - [Microbiologic and immunologic parameters in patients with abscesses of the
      abdominal cavity].
AB  - Dynamic bacteriological examination of abdominal exudate and wound pus after
      operations on 131 patients with abdominal abscesses of various localization
      revealed a variety of microorganisms among which 44.2% were staphylococci, 22.9%
      enterococci, 64.1% Escherichia coli, 34.2% proteus microorganisms, 31.0% Cl.
      perfringens, and 90% nonclostridial anaerobes; certain varieties (phagotypes,
      serogroups) prevailed among them which possessed pathogenetic properties to a
      greater measure than their other varieties. A greater part of the cultures
      obtained from the foci of affection were in various microbial associations (2-6
      types) and were resistant to the widely used antibiotics--penicillin,
      streptomycin, chlortetracycline, and retained their sensitivity to antibiotics of
      the neomycin series and to other agents. Specific antibodies to the causative
      agents and the products of their vital activity accumulated (two-sevenfold)
      during the disease in most patients, and the intensity of their increase depended
      on the development of purulent complications and the patient's age. The dynamics
      of changes of the antibody titer may confirm the etiology of the abscess and be
      an indirect index of the prognosis of the disease.

PMID- 8145461
TI  - [Use of cell cultures in the local treatment of burn wounds].
AB  - The article deals with the results of using cultivated allofibroblasts in topical
      treatment of burn wounds. Allofibroblasts obtained from the derma of burnt
      individuals were transplanted to the burn wounds of 28 patients. In 12 among 15
      patients (80%) with IIIa-IIIb degree burns transplantation induced
      epithelialization of the burns in 12.1 +/- 2.4 days. Thirteen patients had deep
      burns, only in 3 of them with a circumscribed burn area transplantation proved
      effective. Complications of transplantation were encountered in 5 patients-
      rejection of the transplant in 2 and its suppuration in 3 patients.
      Allofibroblast transplantation may be applied as an independent method of
      treatment in IIIa, b degree burns.

PMID- 8145462
TI  - [Surgical correction of hyperlipidemia in the treatment of arteriosclerosis
      obliterans].
AB  - Study of the blood serum lipid spectrum in 870 patients with atherosclerosis
      obliterans showed hypercholesterolemia in 24% and increased atherogenicity
      coefficient in 19%. In view of which, an operation for the formation of a partial
      iliac shunt was conducted in 33 patients with hyperlipidemia to reduce the blood
      lipid level and prevent the advancement of atherosclerosis obliterans. It was
      performed simultaneously with an operation for atherosclerosis obliterans in 15
      of them. Twenty-three patients were studied in late periods, the level of
      atherogenic lipids in the blood was found to be decreased in all of them. The
      effect of the operation was positive in 17 patients, the process progressed in 3
      patients. It is concluded that surgical correction of hyperlipidemia in
      atherosclerosis obliterans is an expedient measure.

PMID- 8145463
TI  - [Surgical treatment of stomach ulcer].
AB  - The choice of the operative method in gastric ulcer is determined by the
      peculiarities of ulcer development mechanism and the role of acid production in
      the process and by oncological reasons. Bearing in mind that acid production is
      of little significance in the pathogenesis of gastric ulcer, while malignant
      degeneration of gastric ulcers is quite a reality, the authors consider resection
      of the stomach to be the most expedient operative method in its ulcer. Among 73
      patients with gastric ulcer 70 (95.94%) were treated by resection of the stomach.
      Depending on the localization of the ulcer, the volume of the resection ranged
      from antrumectomy to gastrectomy. Five (7.14%) patients died after the operation,
      3 from thromboembolic complications and 2 from peritonitis. The late-term,
      results were studied in 53 (81.54%) patients and were found to be good in 44
      (83.02%), satisfactory in 5 (9.43%), and poor in 4 (7.55%) patients. Malignant
      degeneration of the ulcer was encountered in 7 (10%) of the 70 patients who were
      operated on. The authors prefer resection of the stomach with the formation of
      Roux-en-Y anastomosis which prevents reflux gastritis, recurrent ulcer, and the
      development of tumors. This is confirmed by the late-term results.

PMID- 8145464
TI  - [Selective proximal vagotomy in combination with prolonged drug blockade of the
      celiac plexus in the treatment of patients with duodenal ulcers].
AB  - The work deals with the results of SPV in combination with prolonged drug
      blockade of the celiac plexus in 78 patients with duodenal ulcers. The motor
      activity of the antral part of the stomach intensified and its blood supply
      increased after blockade of the celiac plexus. The course of the immediate
      postoperative period improved after SPV and the number of patients with
      hypokinesia of the stomach reduced.

PMID- 8145465
TI  - [Temporary perfusion substitution of liver and spleen functions in patients with
      peritonitis].
AB  - Thirty-one patients with generalized purulent peritonitis of various etiology
      were examined; a new perfusion method with the use of isolated live hepatocytes
      and xenospleen fragments was applied in the intensive therapy complex in the
      early period after a cavitary operation in 16 patients. It is shown that the
      suggested method has significant advantages over the traditional methods in that
      it causes effective detoxification, improves microcirculation, and reduces the
      indicators of the cytologic syndrome. Application of the hybrid system of
      detoxification in patients with peritonitis made it possible to reduce the
      lethality among the most serious patients with infectious-toxic shock and
      polyorganic insufficiency.

PMID- 8145466
TI  - [Duodenal injuries].
AB  - Experience in surgical treatment of 69 patients with open (41) and closed (28)
      injuries to the duodenum (D) is analysed. The wound (rupture) was closed with
      sutures in 52 patients, closure of the wound was supplemented by
      gastroenterostomy in 9 patients, other variants of treatment were applied in 8
      patients. In 7 patients the damage of the D was not detected during the first
      operation. Complications developed in 34.8% of cases, mortality was 27.5%. A
      diagnostic algorithm is suggested which includes along with clinical examination,
      successive radioscopy (-graphy), laparocentesis or laparoscopy, and
      fibrogastroduodenoscopy. The therapeutic and diagnostic program included
      intraoperative transcatheter pneumopressure, standardized operative variants with
      the use of precision suture techniques, and decompressive drainage of the D with
      a fixed catheter. As a result the number of complications reduced by 1.5 times
      and lethality by half. The late-term results were studied in 26 patients, they
      were found to be good in 21 of them.

PMID- 8145467
TI  - [Ogilvie's syndrome].
AB  - In the last 5 years the authors had 10 patients with Ogilvie's syndrome under
      observation. The frequency of the development of the syndrome among all patients
      who were in the department in this period of time was 0.09%, those who underwent
      operation accounted for 0.1%. Mortality was 60%. Seven patients were treated by
      operation. In all patients the syndrome developed in a severe internal disease of
      an operative intervention. The authors encountered the following clinical
      diagnostic signs in these patients: moistened tongue, mild tachycardia, absence
      of hypertrophy of the intestinal wall, and no fecal masses found in the lumen of
      the large intestine on operation.

PMID- 8145468
TI  - [Prevention of infectious complications in heart surgery patients with dalargin].
AB  - The authors studied the effect of dalargin, a Russian produced synthetic analogue
      of regulatory opioid peptides on the incidence, severity, and outcomes of
      infectious complications in cardiosurgical patients with congenital and acquired
      heart diseases. The use of dalargin in the complex of multicomponent
      anesthesiological protection--neuroleptanalgesia, facilitated relative limitation
      of the sequelae of stress-induced secondary immunodeficiency in the form of
      increased risk of the development of postoperative purulent and inflammatory
      diseases. This resulted both in reduction of lethality from infectious
      complications, anterior purulent mediastinitis among others, and in decrease of
      the absolute number and percentage of postoperative complications of infectious
      etiology. This points to the principal possibility of formation by means of
      dalargin of the corresponding level of adaptation to the damaging action of
      surgical stress, which is evidently mediated by optimization of neurovegetative
      protection in particular due to the antistress properties characteristic of the
      synthetic opioid hexapeptide.

PMID- 8145469
TI  - [Treatment of abscesses of the upper abdominal cavity after surgery on the
      liver].
AB  - Complications after 454 various operations on the liver are analysed. Abscesses
      of the upper part of the abdominal cavity (subdiaphragmatic and subhepatic
      abscesses, suppuration of residual cavities after resection of the liver and
      echinococcotomy) developed in 18.5% of patients in the postoperative period.
      Inadequate drainage of the abdominal cavity was among the main causes of such
      complications. The authors suggest an original method for drainage of the
      abdominal cavity after operations on the liver. With its use the number of these
      complications was three times less. It was found that in 40.5% of cases abscesses
      of the upper abdominal cavity may be cured by nonoperative measures, by puncture
      of the purulent cavity under control of ultrasonic examination and introduction
      of drains for subsequent aspiration. A surgical intervention is still the main
      method for the treatment of abscesses of the upper abdominal cavity. The success
      of the operation is determined to a great measure by effective drainage. A
      drainage method is suggested which allowed the time needed for the treatment in
      cases with such complications to be reduced almost by half.

PMID- 8145470
TI  - [Difficulties and errors in diagnosis and treatment of closed trauma to the
      abdominal organs].
AB  - A critical analysis of the difficulties and errors in the diagnosis and treatment
      of closed injuries to the abdominal organs during a period of 30 years is given.
      In the first period (1960-72) diagnostic laparotomy was applied widely in all
      questionable cases, which in 32 out of 252 (12.7%) patients failed to reveal
      injuries to the viscera, but aggravated the general condition and promoted a
      fatal outcome in some patients. Because of diagnostic doubts, 38 (15%) patients
      were kept under observation at the clinic for 6 to 48 hours; in 29 of them the
      operation was delayed, nine patients did not undergo surgery and injury to the
      abdominal organs was recognized only on postmortem examination. Total mortality
      was 32.1% (17.5% in isolated injury and 62.9% in concomitant injuries). During
      the second period (1973-89) 349 patients with similar injuries were under
      observation. With the wide use of laparocentesis and, less frequently,
      laparoscopy in diagnostic difficulties, the number of explorative laparotomies
      reduced to 2.8%, the time for establishing the diagnosis was shortened to 30-60
      minutes, an authentic diagnosis was made in 96% of patients, and mortality
      decreased by 9% due to timely operation (it was 8.5% in isolated and 44.8% in
      concomitant injuries). The author points out that the results of laparocentesis
      and laparoscopy may be pseudonegative in some cases, which may lead to serious
      diagnostic and tactical errors. Similar errors were made in 30 (5%) patients
      during the operation itself because the main rules of examination of the
      abdominal cavity were not observed.

PMID- 8145471
TI  - [Method for gastric resection with end-to-end gastroduodenal anastomosis].
AB  - The authors suggest a method of stomach resection in which the gastroduodenal
      anastomosis is created by applying sutures to the layers after separating the
      sheaths of the organs into layers. The inner sheaths (muco-submucous) of the
      organs are butt joined after their excision almost at the base, while the outer
      sheaths (seromuscular) are sutured with rarely placed crimping sutures. The rare
      placing of the sutures and moderately tight tying of the ligatures prevent
      impairment of tissue nutrition, whereas crimping of the outer sheath provides
      wide contact of the serosa. Narrowing of the anastomosis does not occur because
      the inner sheath is sutured in a butt manner while the ridge formed on the outer
      sheath is outside the lumen. The wound of the anastomosis heals by first
      intention. The method was used in 251 patients with various diseases of the
      stomach and duodenum. Their ages ranged from 13 to 73 years. Most were seriously
      ill. Two patients died, one from the fibrinolysis syndrome, associated with
      massive transfusion of blood, and hepatorenal failure, the other died from
      pancreonecrosis. The sutures of the anastomosis were efficient in both cases.
      Incompetence of the anastomosis sutures was encountered in one patient.
      Incompetence of sutures of the closed part of the gastric stump was diagnosed in
      another patient. Perforation of acute ulcer of the gastric stump occurred in
      still another patient. All of these patients as well as the other patients
      recovered.

PMID- 8145472
TI  - [The use of direct current in cleansing the gallbladder after cholecystostomy].
AB  - The authors developed and introduced into practice a method for the treatment of
      acute complicated cholecystitis. It consists in the creation of laparoscopic
      cholecystostoma and conduction of intracystic electrophoresis of healing agents
      through a drain in the postoperative period. The method was used with a favorable
      results in 8 patients with increased operative risk.

PMID- 8145473
TI  - [Revascularization of the distal sections of the ischemic extremity with transfer
      of the greater omentum to the leg].

PMID- 8145474
TI  - [Successful treatment of a patient with Zollinger-Ellison syndrome by
      hemipancreatectomy combined with selective proximal vagotomy].

PMID- 8145475
TI  - [The clinico-endoscopic observation of early stomach cancer].

PMID- 8145476
TI  - [Giant amebic abscess of the liver].

PMID- 8145477
TI  - [Ogilvie's syndrome in an elderly woman].

PMID- 8145478
TI  - [Local hemostatic preparations made from the natural components of the
      coagulation system (1)].

PMID- 8145480
TI  - [In memoriam S. I. Spasokukotskii (1870-1943)].

PMID- 8145479
TI  - [Hospital enterococcal infection].

PMID- 8145481
TI  - [Monocular diplopia caused by pressure of the upper eyelid on the cornea.
      Diagnosis based on the "Venetian blind phenomenon" in streak retinoscopy].
AB  - BACKGROUND: Abnormal pressure from the upper eye lid can cause a kink in the
      corneal vault along the lid margin. Depending on whether the lower or upper part
      of the lid exerts the higher pressure, the upper segment of the cornea acquires a
      prismatic effect which is base up or down, respectively. This causes a ghost
      image below or above the main image. In patients whose upper eye lid occasionally
      reaches down such that the kink traverses the pupillary area, the ghost image
      appears whenever they raise their lid above its usual position. The purpose of
      the present paper is to describe a retinoscopic phenomenon that allows an easy
      diagnosis of this condition. PATIENTS AND METHODS: About 20 patients with a ghost
      image below or above the main image were examined with a Placido disc, with a
      photokeratometer, and with a streak retinoscope. RESULTS: Photokeratometry
      revealed a slight deformation of the ring reflexes along a horizontal line at the
      border of the upper third of the cornea. This deformation was obvious only in a
      minority of the patients. The retinoscopic findings were more characteristic.
      With the streak horizontal, two or three light bands separated by dark intervals
      were seen in a "with movement", suggesting the impression of a Venetian blind
      being lowered or raised behind the pupil. Because of this impression, the author
      suggests the term ""Venetian blind phenomenon." DISCUSSION AND CONCLUSION:
      Monocular diplopia caused by abnormal lid pressure can be easily diagnosed by the
      "Venetian blind phenomenon". The optics can be explained as follows. Both the
      beams entering into, and emerging out of the patient's eye are being split by the
      prismatic effect of the upper cornea. Principally, this should result in four
      images; since, however, two of them overlay each other, only three separate
      images remain. In cases where the upper cornea is deflected backwards, resulting
      in a prismatic effect base down, the examiner can see all three images. In cases
      where the upper cornea is deflected forwards, resulting in a prismatic effect
      base up, the beams emerging from the patient's eye diverge, and the uppermost
      beam falls upon the examiner above his pupil, so that he can see only two of the
      three images.

PMID- 8145482
TI  - [Use of vertical and horizontal traction sutures in eyelid surgery].
AB  - BACKGROUND: Patients with lid surgery may benefit from traction sutures. However
      no detailed descriptions of the techniques exists. We describe our techniques and
      experiences in patients with cicatricial ectropion and large lid defects.
      PATIENTS AND METHODS: In 33 patients with severe cicatricial ectropion, the wound
      was extended with transtarsal traction sutures before skin grafts or sliding
      flaps were sutured in place. Horizontal traction sutures allowed wound closure in
      7 patients with tumors of the medial canthal area or large traumatic lid defects.
      In all patients monofil 4-0 polypropylene suture material was used. RESULTS:
      Vertical transtarsal traction sutures and horizontal traction sutures did not
      cause any irritations of the lids or wound edges. Postoperative overcorrection of
      the lower lid margin was achieved in all ectropion patients. However, five
      patients required additional surgery. Three patients were operated for bilateral
      cicatricial ectropion simultaneously. Postoperative shrinkage of the free skin
      graft was more accelerated on the side where the transtarsal traction sutures
      were first removed. Horizontal traction sutures allowed wound closure in all
      seven patients who had undergone medial canthal reconstruction and traumatic lid
      repair. CONCLUSION: Traction sutures with monofil 4-0 polypropylene material can
      fixate the lid margins and wound edges in the preoperatively desired position.
      There is evidence that the traction sutures can influence postoperative wound
      contraction. Our technique of transtarsal traction sutures has several advantages
      as compared with previously described techniques.

PMID- 8145483
TI  - [Retrospective study of severe alkali burns of the eyes].
AB  - BACKGROUND: Alkali burns are of special interest because of the rapid and deep
      penetration of alkali into the ocular tissues. PATIENTS AND METHODS: This report
      examines the epidemiology, management and outcome of 42 cases of alkali burns of
      the eye admitted to the eye clinic of the RWTH Aachen from 1985 to 1992. Aspects
      examined were the nature of accident, type of alkali, treatment and
      complications. The intention was to use this information for improvement of
      prevention and treatment of these cases. RESULTS: The age analysis showed the
      greatest at-risk population were the 20-40 year-old patients. 73.8% were
      industrial accidents, 30% happened to builders and labourers, 20% in the chemical
      industry and 20% in machine factories. At home most of the injuries were caused
      by lime and drain cleaners. Sodium and potassium hydroxide produced more extended
      and deeper damages than lime due to their rapid penetration through the ocular
      tissues. A delayed surgical intervention led to a longer time of stay in hospital
      and to a higher number of operations. All eyes could be prevented from melting,
      but an optical rehabilitation (visual acuity > 0.3) was achieved only in a few
      cases (14.5%). CONCLUSION: There is a need to ensure adequate public awareness of
      the danger of alkali burns to the eye. Beside the primary prevention, adequate
      first aid with immediate and continuous irrigation is of paramount importance. A
      uniform concept for the management of these severe cases is necessary including
      an antiinflammatory medical and surgical treatment.

PMID- 8145484
TI  - [Covered rupture of periocular dermoid cysts. Clinico-histologic study].
AB  - BACKGROUND: Dermoid cysts are common periocular tumours that occur in childhood
      and can, in case of rupture, result in persistent granulomatous inflammation.
      Histologically signs of chronical inflammation of the wall of the dermoid cyst
      are occasionally found in dermoid cysts that show no clinical symptoms. The aim
      of this study is to analyze frequency and etiology of this inflammation. PATIENTS
      AND METHODS: The charts of 21 patients that were operated on because of a dermoid
      cyst at Heidelberg University Eye Hospital between 1986 and 1993 have been
      examined concerning anamnesis, clinical symptoms, localisation of the cyst and
      incidents during operation. The dermoid cysts were assessed macroscopically, and
      histologically by means of serial sections (three cuts every 200 microns).
      RESULTS: Histologically 8 patients (38%), of which only one had clinical
      symptoms, showed an inflammation of the wall of the cyst. The serial histological
      sections revealed a hidden rupture, that is a damage of the epithelium with a
      remaining pseudo-capsule of connective tissue, in these 8 patients. Hidden
      ruptures occurred proportionately most often at the age of 20 to 40. All cysts
      with a volume of more than 2197 mm3 showed a hidden rupture. CONCLUSIONS: Hidden
      ruptures seem to be the reason for inflammations of the wall of a dermoid cyst.
      By way of the rupture, the content of the cyst gets into contact with the
      surrounding tissue, which results in a granulomatous reaction to the foreign body
      with remaining pseudo-capsule, to begin with. Etiologically a hidden rupture is
      promoted by the growth of the dermoid cyst and the pubertal enlargement of the
      sebaceous glands in the wall of the cyst. As a hidden rupture may result in a
      complete one with corresponding clinical symptoms, and as the risk to rupture a
      cyst during operation is higher in case of a cyst with hidden rupture, we
      recommend an early operative removal of dermoid cysts, if possible at the age of
      3 or 4, but at least within the first 10 years.

PMID- 8145485
TI  - [Biocompatibility of silicone intraocular lenses].
AB  - BACKGROUND: In order to the biocompatibility of silicone intraocular lenses,
      which is described contradictory in literature, we compared IOLs made of silicone
      caoutchouc and PMMA-IOLs with regards to the presence of macrophages (i.e. giant
      cells or spindle-shaped cells) in a prospective, randomized study. PATIENTS AND
      METHODS: Totally 125 patients were examined 2 months post-operatively with the
      slitlamp in the refractive zone. The single-piece PMMA-IOLs with an open haptic
      used in this study had a 6 mm optical zone and a total diameter of 11 mm; the
      silicone-IOLs were disc-shaped lenses with a total diameter of 9.75 mm and an
      optical zone of 6 or 5.5 mm, resp. RESULTS: Giant cells were observed with 16% of
      PMMA-lenses and 19% of the silicone-lenses. The maximal density of the giant
      cells on the PMMA-lenses at the median was 3/mm2 compared to 2/mm2 on the
      silicone IOLs. Small and spindle-shaped cells were found in 54% of the PMMA-IOLs
      and 46% of the silicone-lenses. The maximal cell density at the median was 10/mm2
      with both lens types. CONCLUSIONS: The differences between the two lens materials
      are statistically non-significant. Thus, silicone caoutchouc and PMMA possess a
      comparable biocompatibility when used as material for intraocular lenses.

PMID- 8145486
TI  - [Radical conjunctivectomy in therapy of malignant melanoma of the conjunctiva].
AB  - BACKGROUND: In tumor excision of large malignant melanomas of the conjunctiva or
      in the excision of widespread precancerous melanosis the development of
      symblepharon is a threatening complication after conjunctivectomy, especially if
      the conjunctival fornix is afflicted. PATIENTS: Three patients with suspected
      nodular melanoma and surrounding precancerous melanosis of the conjunctiva were
      treated by extended excision of the conjunctiva. Instead of a conjunctival graft,
      spontaneous epithelization under the protection of an 'Illig' contact lens was
      achieved. After this, two patients with histologically proven malignant melanomas
      were treated by beta-ray radiation with 90-Strontium. RESULTS: Within four weeks
      after the excision a complete epithelization of the wound occurred and the
      functional as well as the cosmetic results were very satisfying. During the
      follow-up between 12 and 22 months no recurrence of the melanomas and no
      formation of symblepharon was observed. CONCLUSIONS: With regard to these results
      extended tumor excision without conjunctival graft seems to be a reasonable
      therapy for large nodular melanomas and widespread melanosis, while the
      application of an 'Illig' contact lens avoids the formation of symblepharon.

PMID- 8145487
TI  - [Bilateral acanthamoeba keratitis].
AB  - BACKGROUND: Given the protracted clinical course, diagnostic difficulties,
      frequent treatment failures and the increasing incidence, keratitis caused by
      free-living acanthamoeba represents a clinical challenge. PATIENT AND METHODS: A
      37-year-old healthy female who wore gas-permeable contact lenses for ten years
      developed bilateral keratouveitis, pseudodentritic subepithelial infiltrates and
      corneal ring ulcers. Cultures were obtained from corneal scrapings, contact
      lenses and storage container. Medical treatment during the clinical course
      included propamidine isethionate, miconazole, ketoconazole, polymyxin B,
      aminoglycoside antibiotics and corticosteroids. Surgical procedures included
      bilateral penetrating keratoplasty and extracapsular cataract extraction. Each
      corneal button was examined after chemofluorescent staining with calcofluor
      white. RESULTS: Klebsiella oxytoca and Serratia marcescens were grown from
      cultures of the contact lens storage container. Although suspected early in the
      clinical course repeated cultures from corneal scrapings were negative for
      acanthamoeba. Despite transient remission, medical therapy including therapy for
      acanthamoeba could not halt the progression of infection in both eyes. Visual
      acuity deteriorated to light perception and counting fingers, respectively.
      Penetrating keratoplasty was performed 12 and 15 months after the onset of
      symptoms. Histopathological examination allowed identification of acanthamoeba
      cysts in each button. Because of secondary cataract formation cataract-extraction
      with intraocular lens implantation was simultaneously performed in the right and
      subsequently in the left eye. While corneal infiltrates recurred and optic
      atrophy developed due to secondary glaucoma in the right eye, the left corneal
      graft has remained clear. CONCLUSIONS: The case-report demonstrates that
      diagnostic procedures may fail to detect acanthamoeba organisms before obtaining
      a corneal button for histopathologic examination. Decreased corneal sensation
      later in the clinical course after initial pain disproportionately related to
      clinical signs does not exclude the diagnosis of an acanthamoeba keratitis.
      Medical treatment failure may occur despite early initiation of antiparasitic
      therapy.

PMID- 8145488
TI  - [Meningioma of the optic nerve sheath with extensive intraocular growth].
AB  - PATIENT: We report on an elderly female patient with a diagnosis of an optic
      nerve sheath meningioma 11 years after onset of ophthalmological symptoms. 8
      years after diagnosis and consecutive tumour-resection near the orbital apex the
      eye had to be enucleated because of a painful secondary glaucoma. Prior to
      enucleation computed tomography had revealed extra- and intraocular tumour.
      MORPHOLOGY: Morphological investigations showed a neoplasia which had entered the
      eye via the optic nerve head. Besides severe secondary changes there was a
      diffuse tumour spread within the choroid and a "mushroom-like" growth towards the
      vitreous cavity. No differences between extra- and intraocular meningioma were
      found light- and electronmicroscopically.

PMID- 8145489
TI  - [Excentric lentiglobus posterior].
AB  - BACKGROUND: The posterior lentiglobe is a rare anomaly of the lens shape. Two
      cases of excentric protuberance of the posterior capsule are presented. To our
      knowledge, only one description of a similar case exists so far. PATIENTS: An
      eight-year-old girl (diagnosis by routine examination, V.A. 20/20) and a six-year
      old boy (V. A. 20/200, esotropia) are presented. Apart from a persistent
      hyperplastic primary vitreous and a posterior pole cataract a vitreous cyst
      adherent to the posterior surface of the lens has to be considered as
      differential diagnosis. The etiology remains unclear. CONCLUSION: In excentric
      posterior lengtiglobe a good vision is possible. However, if visual acuity is
      impaired by posterior pole opacity or distortion of the spherical surface,
      removal of the lens followed by optical correction (contact lens, intraocular
      lens) of aphakia should be performed.

PMID- 8145490
TI  - ["Physical eyes" for evaluating various intraocular lenses for monocular and
      binocular use].
AB  - We developed a "physical eye system" to evaluate visual impression after physical
      implantation of monofocal and multifocal intraocular lenses (IOLs). The system is
      constructed as two identical astronomical telescopes. The objectives imitate the
      cornea and behind this cornea the IOL is inserted. The image quality represents
      exactly the quality of the intraocular lens.

PMID- 8145491
TI  - [Surgery with the laser scalpel. Physical principles and clinical effectiveness].
AB  - BACKGROUND: The conventional surgical method for cutting vascularized tissue with
      scalpel and scissors may now be improved by use of the laser scalpel. In
      particular, the frequent interruption necessitated and the poor visibility caused
      by bleeding may be mitigated owing to the haemostatic properties of laser light.
      This instrument may be of particular value for tasks involving extrabulbar
      structures, such as extraocular muscles and lacrimal tissue, as well as for
      facial surgery. MATERIALS AND METHODS: The mode of action and physical properties
      of a new laser scalpel are described and its characteristics compared with those
      of other instruments on the market. The probe consists of a clad, sculptured
      silica fibre with a core diameter of 0.6 mm and a conical 0.15 mm-diameter
      cutting tip. Radiation generated by a low cw-Nd:YAG laser module is fed into the
      probe, at the exit point of which a maximal power density of 57 kW/cm2 is
      attained. Radiated laser energy penetrates the tissue as an incision is made,
      thereby inducing an efficient blood flow stasis which is amplified by thermal
      energy diffusing from the immediate surroundings of the scalpel tip. RESULTS: In
      this report, the laser scalpel is implemented for the excision of a vascularized,
      amelanotic, facial naevus. Both the cutting and haemostatic effects were found to
      be excellent, occurrence of the latter phenomenon being supported by
      ultrastructural findings. The healing response was comparable to that observed
      after conventional surgery. CONCLUSION: The new laser scalpel represents an
      inexpensive and effective cutting and haemostatic tool powered by a standard cw
      Nd:YAG laser module, with a wide spectrum of potential applications.

PMID- 8145492
TI  - [Medial canthus pilomatrixoma in an 80-year-old patient].
AB  - An 80-year-old lady noticed a painless "swelling" in the medial canthal region 3
      months. The tumor showed a reddish color due to a recurrent superficial bleeding
      for 2 weeks. Clinically the tumor was supposed to be a super-infected
      keratoacanthoma. The differential diagnosis included an ulcerative basal cell
      carcinoma. Excisional biopsy and reconstruction using a free graft from the
      ipsilateral upper lid were performed. Histopathologically the lesion proved to be
      a "benign calcifying epithelioma Malherbe" (pilomatrixoma). Today, 8 years after
      surgery, there was no recurrence of the tumor. A circumscribed, subepidermal,
      movable reddish or livid tumor of the upper lid, eye brow or of the canthal
      region should be suggestive of pilomatrixoma, not only in young females.

PMID- 8145493
TI  - [Helicobacter pylori: pathogenic role].

PMID- 8145494
TI  - [Viral hepatitis B and AIDS].

PMID- 8145495
TI  - [Cardiorespiratory disturbances in atrioventricular block].
AB  - The paper covers questions of the emergence and progressing of cardiorespiratory
      disturbances in coronary patients with defective atrioventricular conduction. The
      authors characterize central and peripheral hemodynamics in the above patients,
      diastolic ventricular filling, external respiration, the disturbances of which
      were studied in correlation with hemodynamic features and lipid peroxidation. The
      patients were examined for effects on their cardiorespiratory system of
      cardioselective beta-blockers, adrenomimetics, antioxidants, membrane
      stabilizers.

PMID- 8145496
TI  - [Changes of the renin-angiotensin-aldosterone system and immunologic parameters
      in essential and symptomatic arterial hypertension].
AB  - The authors examined 150 patients with pronounced arterial hypertension: 73 with
      essential hypertension, 42 with chronic glomerulonephritis, 26 with chronic
      pyelonephritis and 10 with diabetic glomerulosclerosis. In addition to
      conventional tests, measurements were made of renin activity, levels of plasma
      aldosterone and hydrocortisone, IgA, IgG, IgM, CIC. A significant rise in
      concentrations of aldosterone, hydrocortisone against a significant fall in those
      of plasma renin were registered in all the patients irrespective of the disease.
      Significant differences between the groups by the renin profile, aldosterone and
      hydrocortisone levels were absent. It is suggested that changes in the hormonal
      spectrum and immunological indices are independent of renal affections in
      hypertension, while involvement of renin-angiotensin-aldosterone system in
      hypertension stabilization has no nosological specificity. The pattern of the
      immunity shifts evidences for their important pathogenetic role in maintenance
      and progression of arterial hypertension.

PMID- 8145497
TI  - [Current approaches to conservative therapy of acute infectious lung
      destruction].
AB  - Differential programs of conservative treatment (antibacterial in combination
      with sanatorium) including correction of immune deficiency, detoxication, quantum
      hemotherapy resulted in appreciable responses in 84.8% out of 894 patients with
      acute destruction of the lungs. Radical surgery was performed in 67 (7.5%)
      patients. Specific features of the treatment according to intensive conservative
      schemes are presented for 484 patients with acute pulmonary abscess, 282 with
      staphylococcal pulmonary destruction, 106 with septic pulmonary destruction and
      22 with pulmonary gangrene. Total lethality reached 7.7%.

PMID- 8145498
TI  - [Psychogenic reactions].

PMID- 8145499
TI  - [Effectiveness of lecedil (famotidine) in the therapy of patients with peptic
      ulcer].
AB  - A total of 30 patients (29 with peptic ulcer and 2 with erosive gastroduodenitis)
      received lecedil, a new famotidine blocker of histamine H2-receptors. The effect
      of the drug was not related to the dose regimen (20 mg twice or 40 once a day).
      In good tolerance side effects were not reported. Healing of duodenal ulcer
      occurred within 4 and 5 treatment weeks in 17 (85.0%) and 19 (95.0%) out of 20
      patients, respectively, within 6 and 8 treatment weeks ulcer healed in 5 and 6
      out of 8 gastric ulcer patients, respectively.

PMID- 8145500
TI  - [Role of duodenogastric reflux in the development of duodenal ulcer].

PMID- 8145501
TI  - [Exocrine function of the pancreas in patients with chronic hepatitis and liver
      cirrhosis of various etiologies].
AB  - Exocrinous performance of the pancreatic gland under secretin-pancreozymin
      stimulation was studied in 76 patients with chronic diffuse diseases of the liver
      who were distinguished into 6 groups: those who suffered from chronic persistent
      hepatitis of viral and alcohol origin, chronic active hepatitis of viral origin,
      cirrhosis of the liver of viral and alcohol origin, primary biliary
      hepatocirrhosis. The results obtained were correlated with those from 11 normal
      persons (controls). Out of 76 examinees the disorders of exocrinous performance
      of the pancreatic gland were revealed in 75 persons. The most characteristic
      features were: a decrease in the basal and an increase in the stimulated volume
      of the pancreatic juice; a reduction of both basal and stimulated production of
      bicarbonates; a decrease in the trypsin and amylase fasting levels and their
      increment in the stimulated juice of the pancreatic gland. Disorder in the
      production of bicarbonates was stated as a most characteristic feature in the
      patients both with viral and alcohol origin of the disease but it was mostly
      manifest in the patients with hepatocirrhosis. Pronounced elevation of the
      activity of amylase and trypsin in the pancreatic juice was observed in patients
      with very high activity of disease development and in the patients who
      continuously used large amounts of alcohol. The authors suspected that alcohol
      abuse and the effect of hepatitis virus had an equal pathogenic impact on the
      liver and pancreatic gland.

PMID- 8145502
TI  - [Candidiasis of digestive tract mucous membranes as a marker of malignant
      neoplasms].
AB  - Presents the findings of mycologic examinations of 12 patients with carcinomas of
      various sites. Though such examinations were carried out because of mycotic
      involvement of the mucous membranes of the digestive and respiratory organs,
      profound studies have revealed malignant tumors. A case history is presented. The
      authors come to a conclusion that candidiasis may complicate and mask the course
      of malignant tumors of various sites over all the phases of their development.
      This necessitates purposeful search for a possible tumor in patients with deep
      mycoses.

PMID- 8145503
TI  - [Immunocorrective drugs in the combined treatment of autoimmune diseases of the
      thyroid gland].

PMID- 8145505
TI  - [Arterial hypertension in patients with alcoholic abstinence syndrome and
      delirium].
AB  - Arterial pressure, fear and anxiety affects, urinary excretion of catecholamines
      and plasma renin activity, central hemodynamics were studied in 134 subjects with
      alcoholic abstinence syndrome and delirium. The above syndrome and delirium were
      associated with arterial hypertension termed "reactive". Reactive hypertension
      declined 1-2 days after the patients' getting out of the acute stage of the
      affects. It can be considered as a manifestation of stress-response in
      pathogenesis of which an essential role may be played by plasma catecholamines
      and renin elevation. Hemodynamically, such hypertension is hyperkinetic with a
      tendency to high total peripheral resistance. Correlations were not found between
      the degree of the reactive hypertension and severity of the fear and anxiety
      affects. There was a weak correlation between the affects and heart beat. Apart
      from reactive hypertension, alcoholism is a promotor of essential hypertension.

PMID- 8145506
TI  - [Brain tuberculomas].

PMID- 8145504
TI  - [Therapeutic nutrition and sparing diet therapy in the combined treatment of
      rheumatoid arthritis].
AB  - 93 patients with rheumatoid arthritis (RA) were given diet therapy and unloading
      diets (ULD). Adjuvant diets appeared beneficial for RA patients, allowed
      reduction in antirheumatic drug dosages. ULD are recommended as an alternative
      treatment of RA dependent on the process activity and pattern.

PMID- 8145507
TI  - [Initial experience with bronchoscopy in diphtheria].

PMID- 8145508
TI  - [Right pulmonary aplasia combined with ventricular septal defect of the heart].

PMID- 8145509
TI  - [Fibrous histiocytoma of the pulmonary valves].

PMID- 8145510
TI  - [The serotoninergic system as a link in the pathogenesis of arterial
      hypertension].

PMID- 8145511
TI  - [Amyloidosis of the small intestines].

PMID- 8145512
TI  - [Intrahepatic cholangiectasis (Caroli's disease) as hepatic malformation].

PMID- 8145513
TI  - [Trial of a long-acting preparation Coldact from the firm NATKO to treat upper
      respiratory tract diseases in polyclinics].

PMID- 8145514
TI  - [Some historic and current aspects of the theories about fever (part 1)].

PMID- 8145515
TI  - [Therapy of fecal incontinence in children].

PMID- 8145516
TI  - [Treatment of encopresis in children by therapeutic exercise].

PMID- 8145517
TI  - [Models of man and care. Part 2. The dilemma of medicine and the need of
      nursing].

PMID- 8145518
TI  - [Wrangling about the patient].

PMID- 8145519
TI  - [Language as a remedy].

PMID- 8145520
TI  - [Indirect myocardial revascularization--a supplement to bypass. New vessels from
      a muscle flap].

PMID- 8145521
TI  - [Theory and practice in nursing].

PMID- 8145522
TI  - [The competent Samaritan].

PMID- 8145523
TI  - Genetic analysis in soft-tissue tumors.

PMID- 8145524
TI  - Human Th1 and Th2 cells: functional properties, mechanisms of regulation, and
      role in disease.

PMID- 8145525
TI  - Comparison of cytogenetic abnormalities and deoxyribonucleic acid ploidy of
      benign, borderline malignant, and different grades of malignant soft tissue
      tumors.
AB  - BACKGROUND: Both DNA flow cytometry and cytogenetic analysis have been used to
      study soft tissue tumors. With flow cytometry, the DNA content of a relatively
      large number of cells can be examined, but cytogenetic analysis gives more
      detailed information about genomic changes. EXPERIMENTAL DESIGN: In order to
      compare the advantages and drawbacks of DNA flow cytometry versus chromosomal
      analysis, 92 primary or recurrent malignant, 16 borderline malignant, and 13
      benign soft tissue tumors were karyotyped after short-term culture. DNA ploidy
      was determined by flow cytometry of suspensions prepared from frozen or paraffin
      embedded samples. From 97 patients, 121 samples were analyzed. RESULTS: On the
      basis of the results, four groups were distinguished: DNA-euploid tumors with
      normal diploid karyotypes (group a) or with abnormal (group b) karyotypes, and
      DNA-aneuploid tumors with normal (group c) or abnormal (group d) karyotypes. The
      findings in group b show that structural chromosomal abnormalities or minor
      numerical aberrations of chromosomes are not detected by DNA flow cytometry. In
      group c, the finding of tumors with an aneuploid DNA-profile and cells with
      normal karyotypes is most likely due to overgrowth of fibroblasts during culture
      and subsequent karyotyping of normal cells. CONCLUSIONS: The findings show that
      a) DNA flow cytometry has a higher success rate than karyotyping, b) both
      techniques are complementary, such that DNA flow cytometry gives an "overview",
      whereas karyotyping gives more detailed information; comparison of both
      techniques in individual cases leads to a better understanding of the chromosomal
      events that occurred during oncogenesis, c) histologically low grade tumors are
      generally DNA-diploid, but may have an abnormal karyotype, and d) histologically
      high-grade sarcomas tend to have an aneuploid DNA-profile; they are generally
      more difficult to karyotype.

PMID- 8145526
TI  - Biosynthesis of 12(S)-hydroxyeicosatetraenoic acid by B16 amelanotic melanoma
      cells is a determinant of their metastatic potential.
AB  - BACKGROUND: We have previously demonstrated that the metastatic potential of
      tumor cells can be increased by treatment with exogenous
      12(S)hydroxyeicosatetraenoic acid [12(S)-HETE], a lipoxygenase metabolite of
      arachidonic acid. However, the biosynthesis of the authentic lipid mediator by
      tumor cells, and especially the correlation of its biosynthesis to tumor cell
      metastatic capacity have not been characterized. In addition, a role for other
      mono HETEs in influencing tumor cell metastatic behavior has been suggested, but
      conclusive evidence is lacking. In this study, we analyzed the biosynthesis of
      mono HETEs from arachidonic acid in tumor cells of different metastatic ability
      and correlated biosynthesis to metastatic potential. EXPERIMENTAL DESIGN: The
      biosynthesis of mono HETEs by low and high metastatic subpopulations of B16
      amelanotic melanoma (B16a) cells was analyzed by high performance liquid
      chromatography (HPLC). The identity of biosynthetic 12-HETE was confirmed by gas
      chromatography/mass spectrometry (GC/MS) and its stereochemical structure
      assigned by chiral phase HPLC. The effect of a lipoxygenase inhibitor on the
      biosynthesis of mono HETEs and its effect on metastatic behavior was examined.
      RESULTS: HPLC analysis revealed that low (LM180) and high (HM340) metastatic B16a
      cells exhibited different profiles and efficiencies for conversion of arachidonic
      acid to mono HETEs. LM180 cells produced equal quantities of 12-HETE and 5-HETE.
      In contrast, HM340 cells synthesized predominantly 12-HETE and small amounts of
      15-, 11- and 5-HETEs. At equal concentrations of substrate, four times more 12
      HETE was synthesized by HM340 cells than by LM180 cells. The identity of
      biosynthetic 12-HETE was confirmed by gas chromatography/mass spectrometry and
      chiral phase HPLC demonstrated that it was the S enantiomer. The biosynthesis of
      12(S)-HETE, but not other HETEs, was significantly inhibited by a lipoxygenase
      inhibitor, N-benzyl-N-hydroxy-5-phenylpentanamide. N-benzyl-N-hydroxy-5
      phenylpentanamide, in a dose-dependent manner, decreased the adhesion of HM340
      cells to murine pulmonary microvessel endothelium in vitro and lung colony
      formation in vivo. Furthermore, re-introduction of 12(S)-HETE, but not other mono
      HETEs, to HM340 cells pretreated with N-benzyl-N-hydroxy-5-phenylpentanamide,
      increased their adhesion to endothelium. CONCLUSIONS: Biosynthesis of 12(S)-HETE
      by tumor cells is a determinant of their metastatic potential and inhibition of
      12(S)-HETE biosynthesis in tumor cells may be a crucial target for intervening in
      metastasis.

PMID- 8145527
TI  - An experimental model for ovarian tumor invasion of cultured mesothelial cell
      monolayer.
AB  - BACKGROUND: Peritoneal spread of tumor cells is one of the characteristic
      features of biologic behavior of ovarian cancers. To understand the mechanism by
      which human tumor cell invasion takes place, we have tried to establish an in
      vitro experimental model for ovarian tumor cell invasion of the mesothelial cell
      monolayer. EXPERIMENTAL DESIGN: Mesothelial cells were isolated from normal rat
      mesentery by trypsin digestion and the cells (1 x 10(5)/dish) were cultured in
      Eagle's minimum essential medium supplemented with 10% fetal calf serum. Cultured
      mesothelial cells (M cells) grew forming a pavement-like monolayer. When M cells
      grew to a confluent state, tumor cells (1 x 10(5)/dish) were seeded on M cell
      monolayers and cultured. Four tumor cell lines derived from human ovarian cancers
      were tested for their invasive behaviors. The penetration of M cell monolayers by
      the tumor cells was confirmed by a perpendicular section of the cell layers. The
      number of penetrated single tumor cells and colonies/cm2 was counted under a
      phase contrast microscope after the tumor cell seeding. RESULTS: Several hours
      after the tumor cell seeding, the cells adhered to M cell monolayers and started
      to penetrate by extending pseudopodia-like cytoplasmic processes through
      junctional margins of neighboring M cells, resulting in the formation of
      penetrated single tumor cells that then proliferated to form colonies under the
      monolayer. The number of penetrated single tumor cells and colonies/cm2 increased
      up to 24 hours after the tumor cell seeding, and thereafter stayed almost
      constant. The number increased with the number of tumor cells seeded, when
      counted at 48 hours, and therefore was taken to be the number of tumor cells
      invaded. The in vitro invasiveness of tumor cells varied with the tumor cell
      lines examined. CONCLUSIONS: Application of this system appears to provide rapid
      determinations of the invasive potential of ovarian tumor cells and to make it
      easy to screen substances that modify the invasion of mesothelial cells.

PMID- 8145528
TI  - Alterations in renal tubular extracellular matrix components after ischemia
      reperfusion injury to the kidney.
AB  - BACKGROUND: The kidney is unique in that after ischemic injury to the renal
      tubules, essentially complete regenerative repair can occur. However, the factors
      responsible for renal regeneration are poorly delineated. Despite the importance
      of extracellular matrix components in cell attachment, proliferation, migration,
      and differentiation (all potentially important factors in regeneration),
      alterations in renal tubular extracellular matrix components after renal ischemia
      reperfusion injury have not been examined. EXPERIMENTAL DESIGN: Rats were
      subjected to bilateral renal pedicle clamping for 45 minutes and kidneys were
      taken at various time points for light microscopy and laminin, fibronectin and
      collagen IV immunofluorescence examination. Blood was taken for plasma urea
      nitrogen and creatinine determination. RESULTS: Plasma creatinine and urea
      nitrogen rose rapidly peaking on days 1 to 3 (peak creatinine 3.2 +/- 0.3 mg/dl).
      The corticomedullary junction showed severe tubular necrosis and desquamation.
      Renal corticomedullary tubular basement membrane laminin showed a dramatic
      decrease at 18 hours through 24 to 48 hours postischemia-reperfusion injury,
      followed by a marked increase through day 5. Fibronectin increased markedly at 4
      hours in all areas of the kidney and this continued through day 5. Type IV
      collagen remained unchanged at all time points examined. CONCLUSIONS: This study
      documents alterations in renal tubular basement membrane laminin and fibronectin
      after renal ischemia-reperfusion injury. The ability of the extracellular matrix
      to modulate cell functions of potential importance in regeneration suggests that
      the alterations described may play a role in renal tubular regeneration after
      ischemic acute tubular necrosis.

PMID- 8145529
TI  - Influence of dietary protein/calorie intake on renal morphology and function in
      cats with 5/6 nephrectomy.
AB  - BACKGROUND: Although still controversial, several studies in humans have
      suggested That dietary protein restriction may slow the rate of progression of
      chronic renal failure. Thus, the influence of dietary protein on renal function
      and progression of renal failure has been the subject of numerous studies in
      several animal models of chronic renal failure, including rodents, dogs, and
      baboons. Because of the high incidence of chronic renal failure in aged cats, and
      the high dietary protein requirements of cats, we studied the effects of dietary
      protein intake on renal function, proteinuria, and renal morphology in cats with
      reduced renal mass. EXPERIMENTAL DESIGN: Partial (5/6) nephrectomy was performed
      in 14 young adult female cats. Sham surgical procedures were performed in eight
      control cats. Control cats and cats with 5/6 nephrectomy were randomly assigned
      to diets containing either 27.6% (low) or 51.7% (high) protein and studied for 1
      year. RESULTS: Renal mass reduction by 5/6 decreased glomerular filtration rate
      by 2/3 and significantly increased proteinuria. Cats with remnant kidneys had
      significantly higher systolic and mean blood pressures than control cats.
      Increased dietary protein/calorie intake significantly increased glomerular
      filtration rate and proteinuria in all cats. Glomerular filtration rates remained
      stable in all cats over the year of study. However, high protein/calorie intake
      resulted in significant renal morphologic injury in remnant kidney cats that was
      prevented by dietary protein/calorie restriction. Light and electron microscopic
      glomerular changes in remnant kidney cats fed the high protein diet were similar
      to changes previously reported in rats and dogs with remnant kidneys.
      CONCLUSIONS: Dietary protein/calorie restriction limits proteinuria and
      glomerular injury in cats with remnant kidneys in a fashion similar to that
      reported in rats. However, the remnant kidney model in the cat appeared to be
      associated with a slower rate of progression compared with kidney model in the
      cat appeared to be associated with a slower rate of progression compared with
      rats.

PMID- 8145531
TI  - Estimation of the volume-weighted mean nuclear volume discriminates Spitz's nevi
      from nodular malignant melanomas.
AB  - BACKGROUND: Spitz's nevi are benign melanocytic skin tumors that are usually
      differentiated from nodular malignant melanomas by histopathologic criteria.
      Often, however, the architectural pattern and cytologic features of Spitz's nevi
      and nodular melanomas are similar. Hence, Spitz's nevi may be confused with
      nodular malignant melanomas at the histopathologic level. EXPERIMENTAL DESIGN:
      The determination of volume-weighted mean nuclear volume (Vv) uses a technique
      that permits an unbiased and efficient estimation of nuclear volumes in tissues.
      In this study, Vv was determined in 13 Spitz's nevi and 14 nodular malignant
      melanomas to investigate whether this stereologic approach may be of use in the
      differentiation of these two tumors. Vv was determined by computer-assisted image
      analysis (IBAS 20, Kontron, Germany) on Feulgen-stained sections using
      stereologic estimation of the Vv. RESULTS: The Vv (+/- SD) of Spitz's nevi was
      491.6 micron3 (SD +/- 175.1), whereas nodular malignant melanomas exhibit a
      significantly higher (p < 0.001) Vv of 775.2 micron3 (SD +/- 205.4). This
      difference was even more pronounced when the deeper portions of the lesions
      (Spitz's nevi: 443.1 micron3, SD +/- 142.4; nodular malignant melanomas: 864.1,
      SD +/- 169.6) were investigated. In addition, we found that in relation to the
      depth of the lesions the mean Vv decreased in Spitz's nevi, whereas it increased
      in nodular melanomas. CONCLUSIONS: We found that (i) nodular malignant melanomas
      reveal a larger Vv than Spitz's nevi in general, and (ii) in contrast to
      malignant melanomas, the Vv of nevomelanocytes in Spitz's nevi decreases in the
      deeper portions of the dermis. Thus, Vv may be regarded as a helpful tool for the
      differential diagnosis of Spitz's nevi and nodular malignant melanomas.

PMID- 8145530
TI  - A mouse model for studies of mucosal immunity to vaginal infection by herpes
      simplex virus type 2.
AB  - BACKGROUND: The role of mucosal immunity in defense of the female genital tract
      against pathogens such as herpes simplex virus-2 (HSV-2) is poorly understood.
      Here we explored the use of a new mouse model to determine whether local immune
      events in the vagina of immune animals may protect them against genital herpes.
      EXPERIMENTAL DESIGN: The effect of the estrous cycle, pregnancy, and sex hormones
      on vaginal infection of adult mice by HSV-2 was determined by immunolabeling of
      virus proteins. The immune response to infection was studied by immunolabeling of
      T lymphocytes, B lymphocytes, and plasma cells in the vagina of infected mice.
      RESULTS: Inoculation of attenuated virus (TK-HSV-2) or wild-type virus (TK+HSV-2)
      into the vagina on day 6 of pregnancy or after treatment with Depo-Provera (DP)
      caused infection of the vaginal epithelium. In contrast, these viruses did not
      cause infection after vaginal inoculation at estrus, metestrus, or after
      treatment with Depo-Estradiol. Infected mice showed immunolabeling of virus in
      the vaginal epithelium from 24 hrs to 5 days after virus inoculation. The immune
      response to infection included upregulation of class II MHC antigen in vaginal
      epithelium, CD8+ T cells in epithelium and stroma, and plasma cells and lymphoid
      nodules in the stroma. Mice that were infected with TK-HSV-2 did not exhibit
      infection of vaginal epithelium when challenged 6 weeks later with TK+HSV-2.
      CONCLUSIONS: Progesterone-dominated adult mice become infected after intravaginal
      inoculation with HSV-2, but estradiol-dominated mice are refractory. Vaginal
      infection with attenuated HSV-2 produces immunity that protects mice against
      later infection by wild-type virus. This immunity either prevents infection of
      vaginal epithelium or severely inhibits viral replication in the epithelium. The
      observations suggest that the E/DP-treated adult mouse should be a useful model
      for studies of mucosal immunity to vaginal infection by HSV-2.

PMID- 8145532
TI  - The role of tumor necrosis factor-alpha in the generation of acute phase response
      and bone loss in rats and talc granulomatosis.
AB  - BACKGROUND: Trabecular bone loss is the part of acute-phase response (APR) in
      rats with subcutaneous granulomatous inflammation induced by talc. EXPERIMENTAL
      DESIGN: We investigated the possible involvement of inflammatory cytokine, tumor
      necrosis factor-alpha (TNF-alpha) in the pathogenesis of bone loss and other
      aspects of APR. Intraperitoneal administration of specific neutralizing
      antibodies to TNF-alpha or of recombinant cytokine indicated that TNF-alpha was
      the primary mediator of bone changes, evidence as slower bone elongation rate,
      bone marrow hyperplasia, and decreased trabecular bone volume and osteoblast
      number in tibial metaphysis. RESULTS: Moreover, direct intraosseal administration
      of anti-TNF-alpha antibody neutralized the effect of inflammation on bone. On the
      other hand, the serum indices of the APR (decreased zinc and iron concentrations,
      ACTH and C-reactive protein concentration) were not greatly affected after the
      administration of anti-TNF antibody, except for the normalization of the
      hypercupremia and weight loss. CONCLUSIONS: The data presented in this report
      demonstrated direct involvement of TNF-alpha in the generation of bone
      alterations during the development of APR in rats with talc granulomatosis.

PMID- 8145533
TI  - Immunohistochemical localization of different laminin isoforms in human normal
      and adenomatous anterior pituitary.
AB  - BACKGROUND: Laminin (LM) is an integral component of basement membranes (BM),
      with important roles in various aspects of cell biology. Several different
      isoforms of LM have been described, and each comprises a molecule consisting of
      three subunit polypeptides, the A, B1, B2, M or S chain. EXPERIMENTAL DESIGN: The
      distribution of different LM subunits was studied in human nontumoral anterior
      pituitaries obtained postmortem and in pituitary adenomas by immunocytochemical
      methods using specific monoclonal antibodies. RESULTS: In normal tissue, the A,
      B1, and B2 chains had a ubiquitous localization in both parenchymatous and
      vascular BMs and in the pericapillary connective tissue space also. The S chain
      seemed to have principally a vascular localization, in contrast to the M chain
      that was mostly localized in the parenchymatous BM. The same antigens were
      investigated in 23 human pituitary adenomas of different secretory type, grade
      and invasiveness. In all cases, the five monoclonal antibodies gave a positive
      staining. The presence or the localization of LM chains did not display a
      specific pattern in the adenomas according to their secretory type, grade or
      extent of local invasion. In the adenomas, the anti-A, -B1, and -B2 monoclonal
      antibodies stained the stroma and in particular the vascular BMs as well as the
      sparse elements of parenchymatous BMs when they were present. The staining with
      anti-S antibody was localized in the stroma and around all the blood vessels. In
      contrast, the immunoreactive material to anti-M antibody was associated to the
      sparse fragments of parenchymatous BMs and it delineated the boundary of adenoma
      cells and stroma. Within the stroma, the anti-M antibody immunoreactivity was
      regularly associated with the arterial walls but rarely with the venule walls.
      CONCLUSIONS: The human normal and tumoral anterior pituitary express all five LM
      subunits and thus contain several LM isoforms with different patterns of
      localization. The most striking difference between the human normal and tumoral
      anterior pituitary concerns the peculiar expression of LM isoforms by adenomatous
      neovessels.

PMID- 8145534
TI  - Type II pneumocytes revisited: intracellular membranous systems, surface
      characteristics, and lamellar body secretion.
AB  - BACKGROUND: Type II pneumocytes, the producers of pulmonary surfactant, have been
      extensively studied during the last 20 years because of the importance of their
      metabolism in lung function and integrity. The ultrastructural studies of the
      1970s and 1980s have shown that these cells present unique elements. EXPERIMENTAL
      DESIGN: In this work, we used thin-section, freeze-fracture, and fracture-flip
      electron microscopy techniques to obtain new information on the ultrastructural
      peculiarities of isolated rat type II pneumocytes, focusing our study on the
      intracellular membranous systems and their interrelationships and the
      microanatomy of their plasma membrane during secretory process. RESULTS: In thin
      sections of pneumocytes postfixed with osmium tetroxide and potassium
      ferricyanide, we observed that lamellar bodies (LBs) are usually connected to
      membranes of the endoplasmic reticulum, and seem to emerge and grow from them.
      Unusual connections between the endoplasmic reticulum and mitochondria were
      detected, as well as numerous "bar-like structures" (BLSs), most of them in the
      early stages of development and often generating from the nuclear membrane.
      Membranes of the smooth endoplasmic reticulum that closely follow the outlines of
      mitochondria also appear to be the origin of some BLSs. Possible transition
      forms, BLS--LB, were also detected, although they were rare. New images of the
      surface of the pneumocytes and its changes during LB secretion showed a
      segregation and clearing of membrane particles at the areas of LB extrusion.
      CONCLUSIONS: We propose that LBs can originate directly from membranes of the
      endoplasmic reticulum or from BLSs. An indirect participation of mitochondria
      appears possible. The plasma membrane of pneumocytes displays structural changes
      associated with the secretion of LBs as visualized by a redistribution of
      intramembrane and surface particles.

PMID- 8145535
TI  - Liver regeneration after partial hepatectomy in the rat. Sequential events
      monitored by 31P-nuclear magnetic resonance spectroscopy and biochemical studies.
AB  - BACKGROUND: Little data exist wherein both the 31P nuclear magnetic resonance
      (NMR) signals and biochemical changes associated with hepatic regeneration after
      a 70% hepatic resection have been assessed simultaneously. EXPERIMENTAL DESIGN:
      Two groups of rats were used: one group underwent a 70% partial hepatectomy and
      the second underwent a sham operation. Both groups were followed sequentially for
      192 hours by in vivo serial 31P-NMR spectroscopy of the liver and its
      phospholipid extracts. Liver injury and function were assessed by biochemical
      means. RESULTS: After surgery, a significant reduction in ATP and an increase in
      the phosphomonoester signal for the hepatectomized animals were noted as compared
      with the controls (p < 0.05). The phosphodiester content of the liver in the
      hepatectomized rats declined to nonmeasurable amounts in vivo. The nadir of ATP
      occurred 72 hours after surgery. The area of the phosphomonoester relative to an
      external reference of methylenediphosphonic acid peak increased steadily over the
      first 96 hours, whereas that of the area ratio of the inorganic
      phosphate/methylenediphosphonic increased over the first 72 hours
      posthepatectomy. The intracellular pH declined sharply in the first 3 days,
      followed by a gradual recovery over the next 5 days. Little change in the
      intracellular pH was observed for the control animals. A significant increase in
      the area of the phosphorylethanolamine relative to an internal reference of
      methylenediphosphonic and a reduction in the glycerophosphorylethanolamine and
      glycerophosphorylcholine peaks were noted during the first four post-hepatectomy
      days as measured by 31P-NMR of perchloric acid liver extracts (p < 0.05).
      CONCLUSIONS: It has been found that a concerted reduction in the intracellular
      ATP and intracellular pH coupled with an increase in inorganic phosphate and high
      levels of phosphorylethanolamine occur as a result of hepatic regeneration and
      the physiologic changes induced. These data demonstrated that a coordinated
      pattern of biochemical changes occur with and after hepatic regeneration.
      Moreover, NMR spectroscopy demonstrates an increase in phosphomonoesters and a
      decline in phosphodiesters during hepatic regeneration. These measures and, more
      specifically, the ratio of these two lipid classes may provide a biochemical
      snapshot of the regeneration status of the liver.

PMID- 8145537
TI  - The limiting effect of dichloroacetate on endotoxin-induced liver damage in
      starved rats.
AB  - Dichloroacetate has been shown to have therapeutic effects on sepsis and
      endotoxin shock and to reduce liver damage in rats intoxicated with ethanol or
      carbon tetrachloride. In this study, the effect of dichloroacetate on endotoxin
      hepatitis was investigated. Endotoxin hepatitis was induced by an intraperitoneal
      coadministration of 50 micrograms/kg lipopolysaccharide from Escherichia coli,
      and 200 mg/kg D-galactosamine in starved, male Wistar rats. This treatment
      induced the following changes within 24 hr: an increase in the serum
      aminotransferase activity, histological alterations of the liver including focal
      necrosis of liver cells and inflammatory infiltrates, an increase in blood
      pyruvate and alanine concentrations, and inhibition of starvation ketosis. The
      intraperitoneal administration of 250 mg/kg dichloroacetate 30 min after the
      administration of the toxins partially counteracted all of these changes. The
      administration of dichloroacetate might be useful in coping with hepatic damage
      as well as lacticemia and cardiovascular depression induced by endotoxins.

PMID- 8145536
TI  - Mucosal glutaminase activity and histology as parameters of small bowel
      preservation injury.
AB  - The present study in Lewis rats was designed to assess the predictive value of
      the mucosal enzyme activities of glutaminase, maltase, and xanthine oxidase and
      of histology as parameters to delineate the degree of small bowel preservation
      injury. Small bowel grafts were flushed with saline or a modified phosphate
      buffered sucrose (PBS) solution, stored at 8 degrees C for 1, 6, or 12 hr, and
      transplanted heterotopically. Tissue samples for determination of mucosal enzyme
      activities were taken after the cold storage period, 20 min after reperfusion and
      2 and 7 days postoperatively. Biopsies for light microscopic evaluations were
      obtained at the same time points, but not after cold storage. Glutaminase
      activity was well maintained after cold storage, regardless of the duration of
      preservation. Enzyme activities measured 20 min after reperfusion decreased with
      increasing duration of preservation (saline: R2 = 32.8%; P < 0.01; PBS: R2 =
      52.3%; P < or = 0.001) and with increasing histologic preservation injury.
      Glutaminase activities were predictive for survival of grafts preserved with the
      PBS solution (R2 = 49.6%; P < or = 0.001; sensitivity 92%; specificity 100%),
      while the activities of maltase and of xanthine oxidase failed to do so. The
      degree of histologic preservation injury seen in graft specimens obtained 20 min
      after reperfusion was a good predictor of graft survival with a sensitivity of
      90% for saline-preserved grafts and 92% for PBS-preserved grafts and a
      specificity of 88 and 67%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145538
TI  - The time sequence of injury and recovery following transient reversible
      intestinal ischemia.
AB  - Intestinal mucosal damage and regeneration were examined in rats following
      transient ischemia produced by the occlusion of the superior mesenteric artery
      for 30 min. Animal groups were assigned for harvesting of small bowel specimens
      at 10, 17, and 30 min and 1, 2, 3, 4, 6, 12, and 24 hr post-relief of ischemia.
      Severe damage to the villi was evident already at 10 min postischemia. Thereafter
      a very rapid restitutional process was observed with restoration of villi
      epithelium in 47.6% of the examined animals at 60 min, 75% at 4 hr, and 100% at
      12 hr. This rapid sequence of events should be taken into consideration when
      designing experimental ischemic bowel animal models and possible therapeutic
      modalities.

PMID- 8145539
TI  - Basic fibroblast growth factor in the early human burn wound.
AB  - The role of endogenous growth factors in normal wound healing is not clear. Most
      of the data on growth factors in healing wounds have been obtained from the
      application of recombinant exogenous growth factors to animal and human wounds.
      We describe the immunolocalization of basic fibroblast growth factor (bFGF) in
      the injured dermis of skin from patients with partial and full-thickness burns.
      Three antibodies demonstrate an extracellular staining pattern of bFGF
      corresponding to areas of tissue injury that was most intense in specimens
      collected between 4 and 11 days post-burn injury. In contrast, bFGF staining
      appeared markedly decreased by Postburn Day 17 and was more consistent with
      uninjured tissue in a 30-day-old burn that had virtually reepithelialized. Basic
      FGF staining in the non-burned skin from the same patients was restricted to the
      dermal capillary basement membranes and the sweat glands, which is consistent
      with other reports of immunoreactive bFGF localization in normal adult skin. The
      immunohistochemical results were confirmed with Western immunoblots of the same
      tissue. The major band at 16.5 kDa, which is within the recognized range of the
      bFGF molecule's several forms, was detected in both burned and unburned tissue
      from the same patient. These findings support the hypothesis that bFGF is a
      presynthesized mediator that is stored in either the cells or extracellular
      matrix, is released locally from sites of direct injury, and may be important in
      early wound healing.

PMID- 8145540
TI  - How to improve the uterotomy healing. I. Effects of fibrin and tumor necrosis
      factor-alpha in the rat uterotomy model.
AB  - Suboptimal uterotomy healing following cesarean delivery or metroplastic
      operations may lead to considerable complications. New insights in the biology of
      wound healing and the availability of a variety of biologic response modifiers
      open the possibility to modulate the process of wound healing in order to gain
      clinical benefits. Can uterotomy healing be improved by local application of
      biosubstances? We developed an uterotomy model in the rat and measured the
      bursting pressure at defined times postwounding as a functional parameter of
      wound healing. In addition, the healing process was assessed by serial light
      microscopic histology. Uterotomy healing was investigated in the presence of
      fibrin alone or with fibrin containing tumor necrosis factor-alpha (TNF-alpha
      fibrin) compared to controls. The fibrin matrix incorporated into rat uterotomies
      reduced wound hemorrhage and led to a 45% increase of early (Day 3) bursting
      pressure (not significant). With 20 micrograms TNF-alpha in the fibrin matrix,
      Day 3 bursting pressure was elevated by more than 100% (P < 0.05).
      Histologically, inflammation and granulation tissue formation was markedly
      enhanced. Two micrograms of TNF-alpha/wound did not show any effect and 200
      micrograms TNF-alpha even led to a decrease in early bursting strength. After 1
      week, no differences in bursting pressure or wound histology could be detected
      between uterotomies treated with fibrin or TNF-alpha-fibrin compared to controls.
      The rat uterotomy model appears to be suitable for investigating new biological
      means to improve uterine wound healing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145541
TI  - The effects of pentoxifylline on pulmonary function following smoke inhalation.
AB  - Bronchopulmonary injury secondary to smoke inhalation is a significant comorbid
      factor following major thermal trauma. The present study evaluates the effects of
      pentoxifylline (PTX) on pulmonary function in an ovine model of inhalation
      injury. Following smoke exposure to produce a moderate inhalation injury, 16
      animals were divided into two groups. Group 1 animals (n = 8) were untreated;
      Group 2 animals (n = 8) were treated continuously with pentoxifylline following
      smoke exposure. The animals were observed in the unintubated, awake state for 48
      hr. Cardiopulmonary variables and blood gases were measured serially. Ventilation
      perfusion distribution (VA/Q), analyzed using the multiple inert gas elimination
      technique, and bronchoalveolar lavage (BAL) were performed at 48 hr. The wet to
      dry lung weight ratio was measured following necropsy. In Group 2, the
      progressive hypoxemia observed following smoke inhalation was attenuated with
      less VA/Q mismatching than in Group 1 (P < 0.05). Pulmonary hypertension
      secondary to increased vascular resistance was also attenuated in Group 2 (P <
      0.05). In BAL fluid, polymorphonuclear leukocytes, total protein content, and
      conjugated dienes were less in Group 2 than in Group 1 (P < 0.05). Plasma
      conjugated diene levels were also lower in Group 2 at 48 hr. Extravascular lung
      water and decrease in lung compliance were greater in Group 1. There was less
      morphologic evidence of airway injury in Group 2 compared to Group 1. The
      improvement of pulmonary function following treatment with PTX suggests that this
      agent may be useful in the management of smoke inhalation injury.

PMID- 8145542
TI  - The effect of norepinephrine infusion on oxygen delivery and consumption in the
      canine model.
AB  - Norepinephrine (NE) is used clinically to increase oxygen delivery (DO2) by
      increasing cardiac output (CO). The rate of administration of NE is usually based
      on frequent measurements of blood pressure (BP) and infrequent measurements of CO
      with little regard for oxygen delivery or consumption dynamics. Although the
      ultimate goal of an inotropic drug is to increase DO2 in excess of metabolic
      requirements (VO2), the effect of NE on the DO2/VO2 ratio has not been previously
      studied. In the present investigation, healthy anesthetized dogs were infused
      with various doses of intravenous NE. These dosages were chosen to span the range
      used clinically. NE administration caused a significant primary increase in VO2
      which was dose dependent (P < 0.001). A similar dose-dependent increase in DO2
      was observed (P < 0.001). However, the increase in DO2 minimally exceeded the
      increase in VO2 at lower doses of NE and the relative increase in VO2 exceeded
      the change in DO2 at a dose of 0.04 microgram/kg/min. Minimal advantage to oxygen
      utilization physiology at low doses of NE and a potential deleterious effect at a
      dose of 0.04 microgram/kg/min were observed, therefore, despite associated
      increases in mean systemic blood pressure. The effectiveness of NE administration
      could be most effectively monitored by the mixed venous oxygen saturation (SVO2),
      rather than by intermittent assessment of BP, CO, or DO2.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8145543
TI  - Regulation of TNF-alpha receptor expression on human neutrophils by various cell
      activating factors.
AB  - Since tumor necrosis factor-alpha (TNF-alpha) has been implicated in a wide range
      of inflammatory states, we sought to examine the regulation of TNF-alpha
      receptors on human neutrophils (PMNs). We were particularly interested in the
      relationship of TNF-alpha binding characteristics to various known neutrophil
      priming stimuli such as temperature, N-formylmethionyl-leucyl-phenylalanine
      (fMLP), phorbol myristate acetate (PMA), C5ades Arg, and human recombinant C5a
      (HrC5a). Competition binding studies indicated that there was no significant
      change in receptor number or affinity due to the temperature used for neutrophil
      isolation. PMNs isolated at 4 or 25 degrees C had a single class of receptors
      with a Kd of 83.1 +/- 3.3 vs 90.0 +/- 8.3 pmole/liter and a similar number of
      receptors, 1575 +/- 99 vs 1876 +/- 279 receptors/cell. However, when either group
      of isolated PMNs was further incubated in buffer at 37 degrees C for 15 min, a
      significant increase in Kd (4-37 degrees C, 147.9 +/- 23.7 pmole/liter; 25-37
      degrees C, 165.2 +/- 29.2 pmol/liter) and a decrease in receptor number (4-37
      degrees C, 1116 +/- 86 receptors/cell; 25-37 degrees C, 957 +/- 71
      receptors/cell) were seen. To determine the effect of other activating substances
      such as fMLP, PMA, C5ades Arg, HrC5a, 4 degrees C isolated PMNs were
      used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145544
TI  - Dipyridamole inhibits early wound healing in rat skin incisions.
AB  - In an effort to investigate the significance of platelet aggregation on early
      wound healing, the inhibitory effects of an antiplatelet drug (dipyridamole) on
      tensile wound strength was assessed. The breaking strength of the dorsal
      incisional wounds in Donryu rats both with and without the administration of
      dipyridamole was measured. In experiment I, the intraperitoneal administration of
      dipyridamole (100 mg/kg/day, Group A; 50 mg/kg/day, Group B) and saline (3
      ml/day; Group C) was performed during the periods between the day of incision and
      the excision of the healing wound specimen in a 2.0-cm width on the third and
      seventh postoperative days (POD). The wound breaking strength was 229 +/- 44, 256
      +/- 39, and 352 +/- 38 g/cm2 on POD 3 and 477 +/- 67, 578 +/- 60, and 764 +/-
      31.9 g/cm2 on POD 7, in Groups A, B, and C, respectively. In experiment II, we
      performed the intraperitoneal administration of either dipyridamole (100 mg/kg)
      or 3 ml of saline as a control just before incision (Group a) as well as at 4 hr
      (Group b), and 12 hr (Group c) after incision, and the percentages of tensile
      strength compared with the control were 72 +/- 8, 89 +/- 13, and 103 +/- 23% in
      Groups a, b, and c, respectively. The administration of dipyridamole
      significantly inhibited the wound healing and, therefore, platelet aggregation
      would appear to play an important role in the early phase of wound healing.

PMID- 8145545
TI  - Changes in testicular testosterone and acid and alkaline phosphatase activity in
      testis and accessory sex organs after induction of varicocele in Noble rats.
AB  - The present study was undertaken to determine the effects of surgically induced
      varicocele on testicular androgen production, seminiferous tubular diameter, and
      acid and alkaline phosphatase activities in testis and accessory sex organs in
      adult Noble rats. Testosterone concentrations in plasma and in both left and
      right testis were estimated in both sham-operated and varicocele-induced rats.
      The activities of acid and alkaline phosphatase were measured in both left and
      right testis, seminal vesicle, and ventral prostate gland in varicocele-induced
      and sham-operated rats. The levels of testosterone in plasma in rats with
      varicocele were lower than those in the sham-operated rats. The concentration of
      testosterone in the left testis was lower than that in the right testis in
      varicocele-induced rats while no such differences were observed in sham-operated
      rats. The seminiferous tubular diameter in the left testis is reduced in
      varicocele-induced rats from that in the right testis. In the sham animals,
      testicular acid phosphatase activity was higher in the left testis than the
      right, while in varicocele-induced animals, no differences in acid phosphatase
      activity between left and right testis were observed. In varicocele-created rats,
      the activity of alkaline phosphatase was higher in the left testis than in the
      right while no differences in alkaline phosphatase activity between left and
      right testis in sham-operated rats were observed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8145547
TI  - Systemic administration of interferon-gamma impairs wound healing.
AB  - Interferon-gamma (IFN-gamma), a cytokine that has been shown to upregulate
      macrophage function, has recently been demonstrated to improve outcome when
      exogenously administered in several animal models of injury. Because the
      macrophage is also important in the events that govern wound healing, we
      evaluated the effects of IFN-gamma upon wound healing in a murine model. IFN
      gamma was administered in doses of 937.5-22,500 u synchronous with the creation
      of a left paraspinous wound and then daily. At Day 10, wounds were harvested,
      evaluated for wound disruption strength (WDS), and subjected to morphometric
      analysis. Wounds were also subjected to 36-hr formalin fixation to maximally
      cross-link collagen fibrils and retested for WDS. We found that IFN-gamma
      impaired wound healing at all doses relative to control, and WDS was impaired in
      a dose-dependent fashion. Our highest dose of IFN-gamma (22,500 u) produced a WDS
      only 65% of the control. Morphometric studies demonstrated less collagen
      deposition and a lower degree of neovascularity in IFN-gamma-treated animals. In
      addition, formalin fixation studies suggested that IFN-gamma may impair collagen
      cross-linking. The potential benefits of IFN-gamma in the multiply injured
      patient must be weighed against the possibility that IFN-gamma might
      deleteriously effect events fundamental to wound healing.

PMID- 8145546
TI  - 5-HT receptor subtypes involved in luminal serotonin-induced secretion in rat
      intestine in vivo.
AB  - The purpose of this study was to compare the 5-hydroxytryptamine (5-HT) receptor
      subtypes involved in secretion of water and electrolytes (sodium, potassium, and
      chloride) induced by luminally administered serotonin in rat jejunum and ileum in
      vivo. Ketanserin partially inhibited and ICS 205-930 totally inhibited serotonin
      evoked secretion. Ketanserin induced mild basal secretion while ICS 205-930 alone
      reduced basal absorption. There were no differences in the effects of ketanserin
      or ICS 205-930 on serotonin-induced secretion by rat jejunum versus ileum.
      Neither N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide nor methysergide
      altered the secretory effect of serotonin in rat ileum. The substituted
      benzamides, cisapride, and BRL 24924, and the 5-HT4 agonist, 5-methoxytryptamide,
      induced water and electrolyte secretion. While BRL 24924 did not alter the
      subsequent serotonin-induced secretory fluxes, cisapride slightly inhibited the
      induced secretion. These results suggest that (1) in both segments of the
      intestine, 5-HT2, 5-HT3, and/or 5-HT4 receptor subtypes are involved in the
      regulation of intestinal transport of water and electrolytes under basal
      conditions; (2) serotonin-induced water and electrolyte secretion is mediated by
      pathways involving 5-HT2, 5-HT3, and 5-HT4 receptor subtypes in both rat jejunum
      and ileum; (3) 5-HT1 receptors do not seem to be involved in the mediation of
      intestinal water and electrolyte transport; (4) these effects are similar to
      those described for systemically administered 5-HT.

PMID- 8145548
TI  - Combined thoracic and intra-abdominal injury.

PMID- 8145549
TI  - Fever in an elderly woman.

PMID- 8145550
TI  - Chylothorax.

PMID- 8145551
TI  - Childhood lead poisoning prevention program.

PMID- 8145552
TI  - Hindsight--20/20.

PMID- 8145553
TI  - Communicating with patients about drug interactions.

PMID- 8145554
TI  - Sexual misconduct statement and policy. Policy Statement of the Tennessee State
      Board of Medical Examiners.

PMID- 8145555
TI  - Statement of the Committee on Infectious Diseases Tennessee Chapter, American
      Academy of Pediatrics.

PMID- 8145556
TI  - State sets new rules for preventing transmission of HIV and HBV viruses.

PMID- 8145557
TI  - The fatal flaw.

PMID- 8145558
TI  - Entwined amniotic band and umbilical cords in a diamniotic twin gestation.

PMID- 8145559
TI  - Liver transplantation: results with Vanderbilt's first 25 liver recipients.

PMID- 8145560
TI  - Is sterility by deleterious recessives an origin of inequalities in the evolution
      of eusociality?

PMID- 8145561
TI  - Fast identification of repetitive elements in biological sequences.
AB  - We have developed a fast filtering method for searching repetitive sequences in
      databases that allows the simultaneous identification of different families of
      repetitive elements during the same scanning. It discriminates between repetitive
      elements and non-related sequences by comparing the frequencies of k-words found
      in both groups of sequences. The distance used to sort out the sequences is based
      on a weighting of the k-words, which is obtained by performing a correspondence
      analysis on learning sets of correctly chosen sequences. The identification of
      Alu elements in human sequences is given as an illustration of the method. The
      Alu sequences are divided in four distinct groups of elements: the left and right
      monomers located on the direct and on the complementary strands. The results
      obtained on the test sets show that a very good discrimination is achieved with a
      word length of 6 b.p. Indeed, only 0.5% of the non-Alu sequences were incorrectly
      predicted as Alu elements for a threshold value allowing the identification of
      all Alu monomers. The misclassification of the different Alu monomers (1.4%) in
      the four groups of examples occurs only when the left and the right monomers are
      in the same orientation. Moreover, during the scanning of 63 GenBank sequences
      longer than 10 Kb, all the Alu elements were correctly identified (616 elements)
      and only a few non-Alu sequences were wrongly predicted as Alu elements (22
      fragments). There is a real need for this kind of method since most of the
      repetitive elements are not annotated in the database entries. This method can
      then be used for a systematic screening of new sequences before their insertion
      in databases. It can also allow the creation of specific databases devoted to
      repetitive elements, which is a required step for any further analysis of those
      elements.

PMID- 8145562
TI  - Migration in variable environments: exploring life-history evolution using
      structured population models.
AB  - In this paper, we explore the hypothesis that environmental variability favors
      the evolution of migration. Using the single-locus invasion condition for a novel
      allele in a variable environment, we derive conditions where increased migration
      rates between two sites are favored. We find that while there is a strong
      advantage to migrants entering a resident population with no migration, there is
      little advantage to migrants entering a population where the residents migrate at
      a different rate. Instead of an optimal rate of migration, there is a range of
      favored migration rates. Negative spatial correlation and a population structure
      including more than two sites accentuate the advantage of migration. Extending
      this model to include the effects of developmental delay (e.g. seed dormancy or
      diapause) on the evolution of migration, we find that higher levels of such delay
      reduce the advantage to migrants.

PMID- 8145563
TI  - Threshold conditions for the spread of the HIV infection in age-structured
      populations of homosexual men.
AB  - The age-structure of a population, and the distribution of sexual behavior
      according to age, are significant factors determining the spread of the AIDS
      epidemic. The threshold conditions for age-structured models account for life
      history information, and thus differ significantly from their age-independent
      counterparts. We examine the threshold conditions for four general age-structured
      models of the spread of HIV in a homosexual population: three with random partner
      selection and one with biased partner selection. We consider both discrete and
      continuous risk groups, and the duration of infection. Susceptibility and
      infectiousness are treated separately, and the infectivity varies with duration
      of infection. Through specific examples, we examine the sensitivity of the
      threshold conditions to the population age-structure and the shape of the
      infectivity profile. The effects of each are of the same order of magnitude.

PMID- 8145564
TI  - Singular perturbation theory applied to Markov models for DNA damage caused by
      ionizing radiation.
AB  - The induction of DNA double strand breaks by ionizing radiation, and enzymatic
      double strand break repair or misrepair, are modeled as continuous time Markov
      chains. Systems of partial differential equations for appropriate probability
      generating functions are solved by singular perturbation theory with scaling. The
      zero-th order singular perturbation result coincides with a model recently
      suggested in a biological literature. Higher order terms correct for various
      effects including "overkill". The results are applicable to both sparsely
      ionizing and densely ionizing radiation.

PMID- 8145565
TI  - Modelling the dynamic ventilatory response to hypoxia in normal subjects.
AB  - We have developed a mathematical model to describe the dynamic ventilatory
      response to hypoxia. The ventilatory response to both transient (two to three
      breaths nitrogen) and 3 min step change hypoxic stimuli were measured in ten
      normal subjects during moderate exercise (oxygen consumption 0.96 +/- 0.08 1 min
      1). The simplest model relating ventilation to ear oxygen saturation which
      adequately described the responses in all subjects consisted of two linear
      differential equations in parallel; both using the fall in oxygen saturation as
      input, and with the outputs summed to give the rise in ventilation. One equation
      had a fast time constant (< 3 sec), and the other a slow time constant. Non
      linear terms included were (i) a "saturating" effect, similar to that described
      by the Michaelis-Menten equation, reducing the gain of the equation with the slow
      time constant as oxygen saturation falls, and (ii) "inhibition" or "potentiation"
      of the gain of the equation with a slow time constant as the output of the fast
      time constant equation increased. Repeated measurements in four subjects showed
      intra- and inter-subject variability for all parameters, with significant between
      subject variability for the gain of the fast time constant equation. The final
      model structure is similar to that describing the peripheral chemoreceptor
      mediated hypoxic ventilatory response in anaesthetized cats.

PMID- 8145566
TI  - Multiple regression analysis suggests motifs for class II MHC binding.
AB  - Multiple regression analysis is utilized to predict peptides that bind major
      histocompatibility complex (MHC) class II molecules of the d haplotype. The
      predictor variables, obtained from the primary sequence of protein fragments,
      include pairs of amino acid residues separated by zero to seven intervening
      residues. The resulting models demonstrate strong predictive validity, and have
      interpretations in accordance with recent discoveries regarding the binding
      mechanisms of class I MHC molecules.

PMID- 8145567
TI  - Brownian motion of the end-to-end distance in oligopeptide molecules: numerical
      solution of the diffusion equations as coupled first order linear differential
      equations.
AB  - The Brownian motion of one end of an oligopeptide molecule relative to its other
      end was previously studied by the measurement of non-radiative energy transfer
      between chromophores attached to the molecular ends, and was found to conform to
      a model which describes this motion as a diffusional process in a force field
      (Haas et al., 1978a). The theoretical treatment of this diffusional problem is
      performed here by an approach which is different from the one used previously. In
      this approach advantage is taken of the fact that in the case under consideration
      the rate of change of the concentration of molecules with a given end-to-end
      distance is linearly dependent on the instantaneous concentration at this and
      neighboring end-to-end distances. One thus obtains a set of coupled first-order
      linear differential equations, which can be solved by standard techniques
      involving the diagonalization of the matrix of the rate constants in the above
      set of coupled equations. The concentration distribution at any instant is
      subsequently obtained as a linear combination of the eigenvectors weighted
      according to their respective exponential decay with time with rate constants
      which are related to their respective eigenvalues. Some of the advantages offered
      by this approach are as follows: one does not have to start the procedure from
      the beginning if new initial conditions are desired, and the concentration
      distribution at any given instant is obtained directly without the need of a
      stepwise build-up of the solution with time. The latter point is especially
      useful if one is interested in the asymptotic behavior of the changes in
      concentration at long times, since this behavior can be readily expressed as an
      exponential decay of the longest-lived eigenvector (or the sum of a few
      exponentially decaying eigenvectors which have the longest decay times). The
      above approach is used to treat the energy-transfer experiments performed
      previously by Haas et al. (1978b), as well as to simulate the dynamics of ring
      opening of cyclic oligopeptides and ring closure of linear peptides.

PMID- 8145568
TI  - A cellular automata model for helper T cell subset polarization in chronic and
      acute infection.
AB  - A cellular automata (CA) model has been built to study the interaction between T
      helper subset cells in a secondary lymphoid organ during chronic and acute
      infection. The TH subset cells interacted via short range cytokine-like factors,
      each cell type producing an autocrine factor and another factor which suppressed
      the development and proliferation of the other TH cell type. A cell death term
      was also included such that T cells not restimulated by antigen within a certain
      time died to be replaced with new naive cells. The important parameters in the
      model were the antigen density entering the lymph node and the propensity of the
      antigens to induce naive T cells down a specific TH subset pathway. Many features
      of the response of the CA were found to match those seen in infections known to
      induce TH subset polarization. For example, it could be seen that TH cell subset
      polarization arose as a natural consequence of the dynamic competition between
      TH1 and TH2 cytokines to induce or suppress proliferation and was driven by the
      antigen produced by the pathogen.

PMID- 8145569
TI  - Two new antiinflammatory elemanolides from Centaurea chilensis.
AB  - Two previously undescribed elemanolide esters, the 2-methylpropanoate and 2
      methyl-2-propenoate of 11,13-dehydromelitensin, were isolated in the course of a
      bioassay-guided fractionation from the aerial parts of Centaurea chilensis Hook.
      et Arn., used traditionally to treat 'gout and rheumatism'. The mixture of both
      substances exhibits anti-inflammatory activity in the carrageenan-induced paw
      edema assay.

PMID- 8145570
TI  - Hepatoprotective effects of Eclipta alba on subcellular levels in rats.
AB  - The hepatoprotective effect of the ethanol/water (1:1) extract of Eclipta alba
      (Ea) has been studied at subcellular levels in rats against CCl4-induced
      hepatotoxicity. Ea significantly counteracted CCl4-induced inhibition of the
      hepatic microsomal drug metabolising enzyme amidopyrine N-demethylase and
      membrane bound glucose 6-phosphatase, but failed to reverse the very high degree
      of inhibition of another drug metabolising enzyme aniline hydroxylase. The loss
      of hepatic lysosomal acid phosphatase and alkaline phosphatase by CCl4 was
      significantly restored by Ea. Its effect on mitochondrial succinate dehydrogenase
      and adenosine 5'-triphosphatase was not significant. The study shows that
      hepatoprotective activity of Ea is by regulating the levels of hepatic microsomal
      drug metabolising enzymes.

PMID- 8145571
TI  - Hypoglycaemic effect of Artemisia herba alba. I. Effect of different parts and
      influence of the solvent on hypoglycaemic activity.
AB  - Artemisia herba alba is widely used in Iraqi folk medicine for the treatment of
      diabetes mellitus. Oral administration of 0.39 g/kg body weight of the aqueous
      extract of the leaves or barks produced a significant reduction in blood glucose
      level, while the aqueous extract of roots and the methanolic extract of the
      aerial parts of the plant produce almost no reduction in blood glucose level. The
      extract of the aerial parts of the plant seem to have minimal adverse effect and
      high LD50 value.

PMID- 8145572
TI  - Ethnobotany of Apocynaceae species in Kenya.
AB  - The study of Apocynaceae species used in traditional medicine reveals that 25
      species in 16 genera are of ethnobotanical interest. Nineteen species are
      medicinal, sixteen of which fall under the subfamily Plumerioideae which usually
      has indole alkaloids. The most common category of diseases treated is skin and
      ectoparasitic diseases followed by abdominal diseases, diseases of the head,
      female conditions and venereal diseases. The root is the most commonly used part
      of the plant and it is possible that the alkaloids play an important role in the
      medicinal value of the plants. Many species are used for non-medicinal purposes
      as fruit (Saba comorensis), edible roots (Carissa edulis), poisons (Acokanthera
      schimperi), fodder (Strophanthus mirabilis), wood (Funtumia africana), birdlime
      (Tabernaemontana pachysiphon), ornamentals (Adenium obesum), dye (Carissa edulis)
      and perfume (Wrightia demartiniana).

PMID- 8145573
TI  - Antibacterial, antifungal and anthelmintic activities of root barks of Uvaria
      hookeri and Uvaria narum.
AB  - On a pharmacological screening, substantial antibacterial, antifungal and
      anthelmintic activities were observed for the hexane and ethyl acetate extracts
      of the root barks of Uvaria narum Wall. and Uvaria hookeri King. Chromatographic
      fractionation of these extracts led to the isolation of the triterpenes glutinol,
      glutinone, taraxerol, beta-sitosterol and Annonaceous acetogenins uvariamicins-I,
      II and III mixture, isodesacetyluvaricin, squamocin-28-one, narumicins-I and II
      stereoisomeric mixture, squamocin and panalicin. The acetogenins exhibited
      antimicrobial and anthelmintic activities in their individual screening
      comparable with standard drugs and hence their presence could be attributed to a
      great extent for the biocidal properties of U. narum and U. hookeri extracts.

PMID- 8145574
TI  - The skeletal muscle relaxant action of Portulaca oleracea: role of potassium
      ions.
AB  - An aqueous extract of the stems and leaves of Portulaca oleracea abolishes the
      twitch contraction of the directly stimulated rat hemidiaphragm preparation. The
      effects of the extract mimic qualitatively the action of potassium oxalate--a
      known constituent of Portulaca oleracea--on the diaphragm. Removal of K+ ions
      from the methanol extract by passing it through a cation exchange resin reduced
      the inhibitory effect of the extract. There was a positive correlation between
      the concentration of K+ ions in the extract and the effects of potassium chloride
      of similar molarity. It is concluded that the K+ ion content of Portulaca
      oleracea is at least partly responsible for the relaxant effect observed on the
      isolated rat diaphragm.

PMID- 8145575
TI  - The muscle relaxant properties of Portulaca oleracea are associated with high
      concentrations of potassium ions.
AB  - The juice and aqueous extracts from the plant Portulaca oleracea have been used
      in West Africa for a variety of medical purposes, and extracts were previously
      shown to have muscle relaxant properties on isolated nerve-muscle preparations.
      We have attempted to characterise the components responsible for this activity.
      Ethanolic extracts caused an initial augmentation of twitch height in chick
      biventer cervicis preparations and then blockade which appeared to be mediated by
      an action directly on muscle fibres rather than on neuromuscular transmission.
      Solvent fractionation of the crude ethanolic extract followed by bioassay on the
      chick biventer cervicis preparation showed that muscle paralysis increased with
      increasing polarity: i.e. water fraction > butanol > ethyl acetate approximately
      equal to crude extracts. These fractions contained 28%, 18%, 12.2% and 9%,
      respectively, of potassium by weight of dried extract. Similar concentrations of
      KCl reproduced the same effect as the extracts on muscle activity, and when the
      most active fraction (water fraction) was desalted, it had no neuromuscular
      activity even at 10 times higher concentration than used previously. We conclude
      that the neuromuscular activity of extracts of Portulaca oleracea is caused by
      high concentrations of potassium ions.

PMID- 8145576
TI  - Protective effect of hachimi-jio-gan, an oriental herbal medicinal mixture,
      against cerebral anoxia.
AB  - The protective effect of Hachimi-jio-gan (HJ) against cerebral anoxia was
      investigated with various experimental models in mice. Minimal effective dose of
      HJ which significantly prolonged the survival time was 0.5 g/kg, p.o. for
      normobaric hypoxia and 0.5 g/kg, p.o. for KCN- (4 mg/kg, i.v.) induced anoxia. HJ
      reduced the duration of coma induced by a sublethal dose of KCN (1.8 mg/kg, i.v.)
      in a dose-dependent manner. Furthermore HJ potentiated the anti-anoxic effect of
      physostigmine and the effect of HJ was diminished by the treatment with atropine.

PMID- 8145577
TI  - Plants used in Guatemala for the treatment of dermatophytic infections. 2.
      Evaluation of antifungal activity of seven American plants.
AB  - From 52 plants screened for antifungal activity, 26 (50%) were active against
      dermatophytes. This paper reports further evaluation of seven American plants
      against four pathogenic fungi (Aspergillus flavus, Epidermophyton floccosum,
      Microsporum gypseum and Trichophyton rubrum), the part showing most activity, the
      best solvent and, in three cases, the minimal inhibitory concentration (MIC)
      against the fungus in pure culture. Antifungal activity was confirmed in all of
      the plants, but not all parts; the most active parts were the bark and leaves.
      The most active species were Byrsonima crassifolia, Cassia grandis, Gliricidia
      sepium and Malpighia glabra. Diphysa robinioides, Rhizophora mangle and Cassia
      occidentalis were less active. The most susceptible fungi were E. floccosum and
      T. rubrum; A. flavus was not susceptible. Ethanol was usually the best solvent
      and the MIC of C. grandis, C. occidentalis and D. robinioides was 50
      micrograms/ml.

PMID- 8145578
TI  - Propagation in the AV node: a model based on a simplified two-dimensional
      structure and a bidomain tissue representation.
AB  - A model is proposed to explain mechanisms of propagation in the atrioventricular
      (AV) node of the heart. The model is based on a simplified two-dimensional
      anatomic description of the central node region and on a bidomain tissue model
      for the propagation. The central region is described as a three-tissue
      compartment model; the proximal tissue composed of ANL cells, the central tissue
      composed of N cells and the distal tissue composed of NH cells. The central N
      region is outlined as an unexcitable gap by forcing these cells to behave as
      depressed cells for which the fast ionic currents are inactivated. This model has
      allowed the authors to test the electrotonic gap hypothesis, which explains the
      time-delay properties of the AV node. Typical conduction curves have been
      obtained, as well as common patterns of Wenckebach blocks. Premature stimulus and
      resulting mapping of cell responses in the N region of the model show typical
      membrane potential dissociation in two components. The model has also been
      submitted to several programmed stimulation protocols in documented anterograde
      and retrograde conduction. The results show that the model is valid and covers
      several well known dynamic properties of the AV node.

PMID- 8145579
TI  - Three-dimensional computer modelling system for the study of biological
      structures.
AB  - A three-dimensional computer modelling system has been developed for use in
      biology, and is currently running on a Sun3 computer. The data originate as a
      series of two-dimensional micrographs which are digitised via a TV camera. The
      two-dimensional images are used to select features of interest and to construct a
      three-dimensional model. This model can be viewed in vector or solid format, it
      can be rotated about three orthogonal axes and can be viewed in three dimensions
      as a stereo pair or an anaglyph. The system has been used in a large number of
      projects over the past 10-15 years, for example, to examine physiological and
      nerve structures. The time-consuming part of the process is the selection of
      features, which involves a high level of biological expertise. Present
      developments are concerned with reduction of the time spent in feature
      recognition and involve the introduction of expert systems together with human
      computer interaction to deal with problems of identification.

PMID- 8145580
TI  - Haemodynamic model of a unilateral iliac stenosis with an aortoiliac bypass.
AB  - A hydrodynamic model for the part of the human arterial network below the renal
      arteries has been constructed using specially fabricated distensible tubes and a
      pulsatile pump to simulate an aortoiliac bypass. The experiments and the computer
      model indicated that no 'steal' occurred due to the insertion of the bypass
      graft. Also, the results showed that the length of the stenosis had a non
      systematic apparent effect on the physiological significance of the obstruction
      and that the kinetic power represented only a small percentage of the total
      power. The total power efficiency of the bypass graft was unaffected by its
      elastic properties. The experimental investigation also indicated that the
      pressure drop across the stenosis was considerably larger than the drop
      calculated using the Poiseuille flow relationship when the stenosis was severe.
      Therefore, a critical arterial stenosis value cannot be defined as an obstruction
      of a constant percentage reduction of luminal area. It varies directly with the
      effective cross-sectional area and inversely with the flow rate. The value of
      angiography in assessing the functional significance of any arterial stenosis is
      therefore limited. A better method for evaluation requires quantitative
      measurements of local blood pressure and blood flow, not only at rest, but also
      under conditions creating augmented flows due to exercise.

PMID- 8145581
TI  - Effects of lower-body negative pressure on blood flow with applications to the
      human cardiovascular system.
AB  - The paper reports a theoretical investigation into the effects of lower-body
      negative pressure on blood flow through the human cardiovascular system. The
      human cardiovascular system is modelled as a closed network of arteries,
      arterioles, capillaries, venules and veins of different lengths and cross
      sections. The pumping action is provided by the contraction of the ventricles.
      The model has been analysed using the finite-element method. The pertinent
      equations incorporating the effects of lower-body negative pressure for the
      pressures and flow velocities have been derived, and the quantitative results
      have been computed. Percentage changes in flow velocities, pressure drops and
      conductances under the application of lower-body negative pressure in the various
      segments and organs of the entire cardiovascular system are obtained. The lower
      body negative pressure has no effect on the flow rates in carotid, ulnar and
      coronary arteries, nor on the supply of blood to the upper extremities, kidneys,
      spleen and liver. The major effects are found in the lower extremities.

PMID- 8145582
TI  - In vivo evaluation of visco-elasticity in a biological tube. Part 1. Stress
      relaxation in the female urethra studied by cross-sectional area and pressure
      measurements.
AB  - The urethral response to a sudden forced dilatation was studied by a mathematical
      analysis of the pressure response in ten healthy women. A total of 60
      dilatations, using various sizes and velocities of deformation, were performed in
      the high-pressure zone. The decay in pressure during relaxation proved to follow
      an exponential equation of the following form: Y = Z + C alpha e-t/tau alpha + C
      beta e-t/tau beta, where Z is the equilibrium pressure, C alpha and C beta are
      pressure decay, and T alpha and T beta are time constants. The time constants
      were unaffected by the circumstances of dilatation, whereas all the other
      parameters were correlated to size or velocity of dilatation, or both. The time
      constants showed a fairly high reproducibility when repeated after one weak. The
      method is presumed to characterise the tissue composition of the periluminal
      tissue layers and may prove useful in the evaluation of the normal urethral
      sphincter function. Furthermore, it may prove of value in the elucidation of the
      pathophysiology of stress urinary incontinence.

PMID- 8145583
TI  - In vivo evaluation of visco-elasticity in a biological tube. Part 2. Application
      of a mechanical model.
AB  - Based on a theoretical model, the urethral stress-relaxation response following a
      sudden forced dilatation was studied in ten healthy female volunteers. The energy
      dissipation following a sudden urethral dilatation proved to follow the function
      Y = Z + C alpha e-t/tau alpha + C beta e-t/tau beta. Hence, a mechanical model
      was chosen, consisting of two Maxwell elements and one Hooke element coupled in
      parallel. The decay in force following deformation may be described as F = F(o)
      exp (-t.E/eta) for each Maxwell element. Thus, it was possible to determine the
      elastic E and viscous eta coefficients for the participating mechanical
      equivalents in the model, and thereby quantitatively describe the visco-elastic
      properties in the urethra. The reproducibility of the elastic and the viscous
      coefficients proved to be fairly high, and they seemed to be unaffected by the
      size of dilatation. On the other hand, the rate of dilatation clearly influenced
      the computed parameters. However, this phenomenon was easily explained by the
      duration of the deformation, which allowed the viscous elements to move before
      any measurements were performed. The present method permits in vivo evaluation of
      the elastic and viscous properties of the urethra, as well as other accessible
      biological tubes, and may be of value in the description of normal physiological
      and pathophysiological behaviour of the structures studied.

PMID- 8145584
TI  - Analysis of air flow patterns in the human nose.
AB  - The nasal cavity is the main passage for air flow between the ambient atmosphere
      and the lungs. A preliminary requisite for any investigation of the mechanisms of
      each of its main physiological functions, such as filtration, air-conditioning
      and olfaction, is a basic knowledge of the air-flow pattern in this cavity.
      However, its complex three-dimensional structure and inaccessibility has
      traditionally prevented a detailed examination of internal in vivo or in vitro
      airflow patterns. To gain more insight into the flow pattern in inaccessible
      regions of the nasal cavity we have conducted a mathematical simulation of
      asymmetric airflow patterns through the nose. Development of a nose-like model,
      which resembles the complex structure of the nasal cavity, has allowed for a
      detailed analysis of various boundary conditions and structural parameters. The
      coronal and sagittal cross-sections of the cavity were modeled as trapezoids. The
      inferior and middle turbinates were represented by curved plates that emerge from
      the lateral walls. The airflow was considered to be incompressible, steady and
      laminar. Numerical computations show that the main air flux is along the cavity
      floor, while the turbinate structures direct the flow in an anterior-posterior
      direction. The presence of the turbinates and the trapezoidal shape of the cavity
      force more air flux towards the olfactory organs at the top of the cavity.

PMID- 8145585
TI  - Experimental acquisition system for impedance tomography with active electrode
      approach.
AB  - An experimental system for impedance tomography has been constructed. The
      acquisition system uses 16 multifunctional active electrodes, each including a
      current source and a voltage buffer. Images of active and reactive parts of
      different target impedances in a phantom filled with liquid have been obtained.
      The system performance has been compared with those of other systems using either
      a mesh phantom or rods as point sources used for the determination of the
      modulation transfer function.

PMID- 8145586
TI  - Processing MRI data for electromagnetic source imaging.
AB  - Estimation of the source of activity in the brain from electro- and magneto
      encephalographic measurements is becoming increasingly common. Structural
      information could assist in improving the calculation of the sources as well as
      providing the context of the source location. Magnetic resonance images are very
      useful for this purpose, but they still need to undergo various processing steps.
      The paper describes in detail a practical method for full automatic processing of
      MRI images of a head, including segmentation of the images and triangulation of
      the surfaces.

PMID- 8145587
TI  - Grasp synthesis for upper-extremity FNS. Part 1. Automated method for
      synthesising the stimulus map.
AB  - Functional neuromuscular stimulation (FNS) has been used in open-loop upper
      extremity neuroprostheses to provide grasp and release for quadriplegic
      individuals. A principal issue in implementation of the open-loop neuroprosthesis
      is the synthesis of the grasp stimulus map, which is the relationship between the
      input control signal and the output stimulus applied to each electrode. The goal
      of this project was to develop a method of stimulus map synthesis which
      compensates for the influence of the electrode-position-dependent recruitment
      properties on the grasp output, and which can be performed using automated
      procedures. A method called the external moment grasp synthesis procedure (GSP)
      has been developed which meets these criteria. The GSP uses an external moment of
      model of the hand which describes the interaction between the active moments
      produced by electrical stimulation, the passive joint moments and the total joint
      moment and angle. The GSP was used to develop the stimulus map for three
      paralysed subjects, and in all cases the GSP-generated grasp patterns had lower
      errors than grasp patterns developed using the previously implemented rule-based
      method of stimulus map synthesis. The GSP was successfully implemented by
      computer and was able to compensate for the effects of the electrode recruitment
      properties on the grasp pinch force.

PMID- 8145588
TI  - Grasp synthesis for upper-extremity FNS. Part 2. Evaluation of the influence of
      electrode recruitment properties.
AB  - Functional neuromuscular stimulation (FNS) has been used in upper extremity
      neuroprostheses to provide grasp and release for quadriplegic individuals. The
      goal of this project was to determine the electrode/muscle input/output
      characteristics with the greatest influence on the grasp output. This was
      evaluated by simulating the grasp synthesis procedure, using a model of the
      electrode/muscle output as a function of stimulus level and joint angle. The
      parameters of this model were determined from experimental data from 112
      electrodes. The grasp output for 500 different modelled pairs of electrodes were
      analysed, with each pair consisting of a thumb flexor and a thumb extensor. The
      simulation results indicate that the most influential electrode input/output
      characteristics are the output stiffness, defined as the change in force output
      for a unit change in joint angle at a constant level of stimulation, and the
      length dependency mean-squared error. Recruitment gain was found to be of
      secondary influence on the grasp output, and the threshold, force direction and
      non-linearity of the stimulus level to force relationship were found to have
      little influence on the grasp output. These results establish criteria for
      electrode selection and implantation for use in upper extremity FNS.

PMID- 8145589
TI  - Non-invasive measurement method for hardness in muscular tissues.

PMID- 8145590
TI  - Detecting intravascular gas bubbles in ultrasonic images.

PMID- 8145592
TI  - Dynamic Levkov-Christov subtraction of mains interference.

PMID- 8145591
TI  - ETMF-polymer transducer as a detector of respiration in humans.

PMID- 8145594
TI  - Designing ECG sub-band coders.

PMID- 8145593
TI  - Thermally controlled water-filled mattress for warming preterm infants: a
      physical assessment.

PMID- 8145595
TI  - Plastic organ models fabricated from MR images using lasers and photopolymers.

PMID- 8145596
TI  - Safety considerations concerning the minimum threshold for magnetic excitation of
      the heart.

PMID- 8145597
TI  - Small area variations in hospitalization rates: how much you see depends on how
      you look.
AB  - This research investigates the degree that estimates of the magnitude of small
      area variations in hospitalization rates depend on both the estimation method and
      the number of years of data used. Hospital discharge abstracts for patients 65
      and older from acute care hospitals in Massachusetts from 1982 to 1987 were
      analyzed. The SCV statistic, the approach used in many current small area
      variation studies, and empirical Bayes (EB), an approach that adjusts more fully
      for the effect of random variation, were compared. EB estimates based on 3 years
      of data were best able to predict future area-specific hospitalization rates.
      Compared to EB estimates using 3 years of data, the SCV statistic with 1 year of
      data overestimated the median amount of systematic variation by over 70% for the
      68 conditions studied; with 3 years of data, the SCV overestimated the median by
      55%. Regardless of method, the same conditions were identified as relatively more
      variable and the same geographic areas were found to have higher than expected
      hospitalization rates. The magnitude of differences in hospitalization rates
      depends on how the data are analyzed and how many years of data are used.
      Hospitalization rates across small geographic areas may vary substantially less
      than reported previously.

PMID- 8145598
TI  - Evaluating the message: the relationship between compliance rate and the subject
      of a practice guideline.
AB  - To explore the relationship between providers' compliance and some key aspects of
      the clinical messages in practice guidelines, studies published in the English
      language medical literature between 1980 and 1991 were retrieved through MEDLINE
      and through relevant review articles in the field. All published studies
      providing compliance rates with practice guidelines and endorsed by official
      organizations were eligible for the study. The clinical content and the reported
      compliance rate were gathered for each recommendation in the 23 studies selected.
      The medical and surgical procedures addressed by 143 recommendations were
      identified according to specialty area, type of procedure (diagnostic, surgical,
      etc.) and were independently classified by the authors as being high or low on
      characteristics thought to influence diffusion:complexity, trialability and
      observability. The mean compliance rate with the 143 clinical recommendations was
      54.5% (95% CI: 50.2%-58.9%), with those in the specialty areas of cardiology and
      oncology showing the highest compliance (mean 63.6% and 62.2%, respectively).
      Recommendations concerning procedures with high complexity had lower compliance
      rates than those low on complexity (41.9% vs. 55.9%; P = 0.05), and those judged
      to be high on trialability had higher compliance rates than those low on
      trialability (55.6% vs 36.8%; P = 0.03). Overall, all the characteristics of the
      clinical recommendations considered in the practice guidelines could account for
      no more than 47% of the observed variability in compliance rates. The target area
      of practice and the complexity and trialability of the recommended procedure
      appear to be useful, if partial, predictors of the level of compliance with a
      practice guideline.

PMID- 8145599
TI  - The costs of interrupting antihypertensive drug therapy in a Medicaid population.
AB  - This research explores the association between the interruption or termination of
      antihypertensive drug therapy and total health care costs among non
      institutionalized Medicaid patients older than age 40 who survive the first year
      after treatment. Multivariate regression analysis was used to estimate the
      statistical relationship between post-treatment costs and patient demographic
      characteristics, prior use of services, the type of medication used as initial
      therapy and whether the patient maintained continuous therapy. Paid claims data
      from the California Medicaid (Medi-Cal) program were used in the analysis. Total
      cost of health care in the first year after the initiation of drug therapy was
      the primary outcome variable. Components of total costs (e.g., hospital,
      outpatient and physician services, prescription drugs) were also investigated.
      Nearly 86% of new antihypertensive drug therapy patients interrupted or
      discontinued purchasing any form of antihypertensive medication during the first
      year. Patients with interrupted antihypertensive drug therapy consumed an
      additional $873 per patient (P < .0001) in health care during the first year, not
      counting a reduction in prescription drug cost of $281 (P < .0001). Increased
      costs were primarily due to increased hospital expenditures of $637 (P < .0002).

PMID- 8145600
TI  - Health care utilization: the effect of extending insurance to adults on Medicaid
      or uninsured.
AB  - Current health care system reform proposals center on reducing the number of
      uninsured by extending private health insurance coverage. Discussion has also
      included enrolling Medicaid recipients in private programs. Much of the
      deliberation concerning extending coverage has centered on cost, but largely has
      not addressed the implications for health care utilization by these groups. If
      private insurance is extended to those currently uninsured as well as the
      Medicaid population, what impact will it have on utilization? Using data from the
      1987 National Medical Expenditure Survey, the results of this analysis show that
      utilization would increase for the uninsured if private insurance benefits were
      extended, whereas utilization would decrease for those with Medicaid, however,
      the magnitude of the increase depends on the type of care.

PMID- 8145601
TI  - Substitution laws, insurance coverage, and generic drug use.
AB  - This study examined the role of various policies (drug product substitution laws)
      that are usually motivated by cost containment objectives of insurers in
      facilitating entry by generic firms. Using data for six Canadian provinces over
      the years 1981-1988, we evaluated the impact of specific aspects of substitution
      laws on the level of generic use. We find that formularies and the passage of
      time are not significant determinants of substitution levels. Legal liability,
      mandatory product selection, deductible and co-payment schemes, and consumer
      awareness were found to be important variables. Price responsiveness of generic
      drugs is indicated but the evidence is not strong.

PMID- 8145602
TI  - Quality of care for depressed elderly pre-post prospective payment system:
      differences in response across treatment settings.
AB  - We evaluated the quality of care for depressed elderly patients (n = 2,746)
      hospitalized in general medical hospitals (n = 297) before or after
      implementation of Medicare's Prospective Payment System, focusing on whether the
      response to time period differed for hospitals that in the post-PPS period had no
      psychiatric unit, an exempt psychiatric unit, or a nonexempt unit, and by ward
      placement within hospitals with psychiatric units. Quality of care increased over
      time, and for most measures of quality of care the level of improvement did not
      differ significantly across different types of hospitals or by ward placement.
      The intensity of use of therapeutic services, such as rehabilitation, occupation,
      or recreation therapy, increased over time, particularly in nonexempt psychiatric
      units and hospitals without psychiatric units, such that these locations caught
      up some over time in the level of use of these services to the level for exempt
      psychiatric units. Several outcomes of care improved over time, and the degree of
      improvement in the rate of inpatient medical and psychiatric complications and
      other outcomes was significantly greater for psychiatric units that were exempt
      post-PPS than for nonexempt treatment locations.

PMID- 8145603
TI  - A method for adjusting capitation payments to managed care plans using
      multivariate patterns of health and functioning: the experience of Social/Health
      Maintenance Organizations.
AB  - A multivariate procedure for identifying case-mix dimensions from discrete health
      variables is presented. Since the dimensions are generated only from health use
      data and not service use data, they can be used for adjust capitation rates to
      provide incentives to treat persons not currently well integrated in standard
      health care system (e.g., very ill persons, the uninsured) or to promote specific
      health outcomes. The procedure is illustrated with data from Social/Health
      Maintenance Organizations (S/HMO) since they provide both acute and long-term
      care (LTC) services. Thus, case-mix measures to adjust S/HMO reimbursements have
      to represent both medical conditions and the degree, and type, of functional
      impairment. From 31 health and functioning items, six case-mix dimensions, and
      scores for individuals on each, were calculated. The multivariate distribution of
      scores in S/HMO enrollees, and in Medicare eligible, comparison samples, were
      examined in each site to see how their health differed. S/HMO enrollees were
      healthier and less frail than persons remaining in the Medicare FFS system. Such
      differences are important in adjusting capitation rates to provide incentive to
      accept clients with complex health problems.

PMID- 8145605
TI  - Differences in hospitalizations among seasonal migrants, adjacent-state and in
      state aged Medicare beneficiaries.
AB  - Hospitalized snowbirds had stays that were similar to those of in-state
      beneficiaries in terms of case-mix and intensity. However, snowbirds had much
      less intense hospitalizations than beneficiaries from adjacent states who often
      required technology-intensive surgery.

PMID- 8145604
TI  - Assessing adherence to asthma medication and inhaler regimens: a psychometric
      analysis of adult self-report scales.
AB  - Poor adherence to recommended regimens is a substantial problem in the clinical
      management of adults with asthma and other chronic diseases. Research on
      adherence assessment is complicated by methodological difficulties including
      limitations associated with the use of self-report measures. In this study,
      psychometric techniques were used to analyze two self-report scales for assessing
      adherence to recommended medication and inhaler use regimens in adults with
      asthma. Results indicated that the two scales had standard deviations large
      enough to detect variation adherence, had adequate reliability, and reflected the
      impact of an intervention designed to improve adherence. The results supported
      the usefulness of these scales for research on adherence. Additional analyses
      indicated that the two scales could be combined if the research goal required an
      overall measure of adherence.

PMID- 8145606
TI  - Protection against dog distemper and Dogs Protection Bills: the Medical Research
      Council and anti-vivisectionist protest, 1911-1933.

PMID- 8145607
TI  - The Bethel at Norwich: an eighteenth-century hospital for lunatics.

PMID- 8145608
TI  - The cult of relics: Pasteur material at the Science Museum.

PMID- 8145609
TI  - The hookworm epidemic on the plantations in colonial Sri Lanka.

PMID- 8145610
TI  - Max Schultze and the living, moving, phagocytosing leucocytes: 1865.

PMID- 8145611
TI  - [Staple sutures--resorbable or metal?].

PMID- 8145612
TI  - [Morphology and healing of skin repair in abdominal wall defects. An animal
      experiment study].
AB  - The aim of the experimental study was to investigate morphology and wound healing
      following the skin plasty ("Kutisplastik") technique originally introduced by
      Loewe [11] and Rehn [17] under different conditions. We wanted to clarify the
      mechanism and development of revascularisation. RESULTS: The familiar phases of
      wound healing take the usual course after a skin plasty. In the exsudative
      reaction the cutis is covered with fibrin fibres. This leads to the development
      of granulation tissue. The cellular reaction takes place in two parts: first
      comes the ingrowth of capillary bundles and vessels in the collagen network of
      corium; revascularization is complete within 14 days after the operation. This is
      followed by the immigration of granulocytes and macrophages into the graft. The
      release of enzymes leads to the lysis of epidermal structures, cutaneous
      appendages and ultimately to collagen fibres of corium. There is also
      proliferation from fibroblasts. Genesis from new collagen fibres is then observed
      as scar tissue. The skin plasty technique involves turning the epidermal side of
      the graft to the peritoneum and suturing it under the highest tension possible to
      the surrounding healthy fascia. This course of healing is seen only with such
      high-tension suturing. Experimental nontension suturing has led to failure of
      skin plasty for abdominal wall defects.

PMID- 8145613
TI  - Donor criteria in hepatic transplantation.

PMID- 8145614
TI  - [The value of duplex sonography after orthotopic liver transplantation.
      Experience with 44 patients].
AB  - In a prospective study, 44 patients (11 women, 33 men) who had received
      orthotopic liver transplants underwent a total of 196 consecutive duplex Doppler
      ultrasound examinations. The aim of the study was to evaluate the correlation
      between the pulsatile flow index (PFI) and the damping index (DI) as far as
      complications as rejection or cholangitis were concerned. The patients were
      examined five times each on average. The PFI and DI were measured in the hepatic
      artery, the portal vein and the hepatic veins. The findings were compared with
      the clinical course (cholangitis, rejection) and the histomorphological diagnosis
      as determined in biopsy specimens. In biopsy-proven rejection episodes, the
      sensitivity of the PFI in the hepatic artery was 69.4%, the specificity 72.2%.
      The sensitivity of the DI in the hepatic vein was 89.4%, the specificity 89.1%.
      Combining the two, specificity was more than 90%. PFI and DI in the portal vein
      bore no apparent relation to clinical course or histomorphological diagnosis. We
      found duplex Doppler ultrasound extremely beneficial in determining the timing
      and indication for liver biopsy. In addition, this simple examination, which can
      be performed as often as desired, accurately shows the transplanted liver's
      response to measures taken to counter rejection.

PMID- 8145615
TI  - [The unreamed tibial intramedullary nail in treatment of tibial fractures-
      initial experiences].
AB  - The unreamed tibial nail (UTN) combines the advantages of the external fixator
      (preservation of the cortical blood supply) with that of conventional
      intramedullary nailing (closed system, high patient comfort, no pin problems) in
      the treatment of the lower leg fracture [5]. Within 1 year (III/92 to III/93) 31
      closed and 2 open fractures were stabilised with UTN. In 67% (22 persons) we
      found fractures of the A1, A2 and A3 types according to the AO classification. In
      6 patients there was a combined lesion with involvement of the ankle joint. A
      follow-up of 27 patients was done, extending to an average of 6 months
      postoperatively. The clinical and radiological results were excellent in 26;
      average fracture healing time was about 12-14 weeks.

PMID- 8145616
TI  - [Effect of diagnostic imaging techniques on choice of therapy and prognosis of
      traumatic pancreas and duodenal injuries].
AB  - 27 patients with pancreatic and 8 with duodenal injuries were studied, 66% of
      whom had associated abdominal injuries. Peritoneal lavage was performed in 10
      cases, and ultrasonography in 15. Laparotomy was considered to be indicated on
      the basis of the results in 9 cases of peritoneal lavage and in 12 cases of
      ultrasound examination, but in only 1 case and 2 cases, respectively, did the
      findings constitute the only reason for performing a laparotomy. Pancreatic and
      duodenal injuries were directly confirmed by ultrasonography and computer
      tomography only in a minority of cases. The morbidity of pancreatic and duodenal
      injuries was 66% and 25%, respectively, and lethality, 19% and 25%. Despite
      modern imaging techniques, clinical examination is of paramount importance for
      the decision as to whether operative therapy is indicated; delay leads to
      increased morbidity and lethality.

PMID- 8145617
TI  - [Long-term animal experiment analysis of the use of resorbable staple sutures in
      partial gastrectomy].
AB  - In animal experiments with a 12-month follow-up, the safety and compatibility of
      absorbable staple lines following gastrointestinal surgery were analysed. In two
      groups of pigs, partial gastrectomies with gastroduodenostomy (Billroth I, n =
      10) or gastrojejunostomy (Roux-en-Y, n = 12) were performed, and Lactomer-a
      copolymer of glycolic acid and lactic acid-staple lines were used for closure of
      the lesser curvature of the stomach and the duodenal stump. Application of the
      staple lines caused no problems and was safe. In 1 of the 22 pigs, which died of
      an ileus 9 days postoperatively a suture dehiscence (4.5%) at the lesser
      curvature of the stomach was observed. Macroscopic examination showed no major
      inflammation around the staples. Microscopically complete absorption of the
      Lactomer staples without extensive scarification in the gastrointestinal wall
      could be demonstrated 12 months postoperatively. Our results yielded no
      contraindications for the clinical use of absorbable staple lines in
      gastrointestinal surgery. The manufacturer has given advance notice of smaller
      staples, which it is considered will be an advantage.

PMID- 8145618
TI  - Intraoperative monitoring of intact PTH during surgery for primary
      hyperparathyroidism.
AB  - The intraoperative differential diagnosis between adenoma and hyperplasia during
      surgery for primary hyperparathyroidism (pHPT) is sometimes difficult. Several
      methods have been proposed to aid the surgeon in deciding on the amount of
      parathyroid tissue to be resected. We examined the use of intraoperative
      monitoring of intact PTH in 47 patients operated upon for pHPT. The highly
      sensitive assay for intact PTH was modified to permit a total turn-around time
      from gland excision to obtained result of about 60 min. The correlation (r)
      between the results of the modified and the conventional method, which requires
      24 h of incubation, was 0.98. At 15 min after removal of the parathyroid adenoma
      the levels of intact PTH had decreased by [mean (SD)] 85 (11)%. A decrease of 63%
      in intact PTH in patients with parathyroid adenoma predicted with 95% confidence
      the 4 patients with primary hyperplasia as not having parathyroid adenoma. We
      conclude that intraoperative measurement of intact PTH could be a valuable
      adjunct to surgical skill, especially for reoperative parathyroid surgery.

PMID- 8145619
TI  - [Congenital duodenal stenosis in adulthood].
AB  - A high-grade duodenal stenosis in adults can, in rare cases, be congenital, and
      its cause is found in an intraduodenally sited membrane. The anamnesis reveals
      growth disorders with vomiting and meteorism and abdominal complaints. A
      perforation opening in this membrane is the reason for survival into adulthood.
      The X-ray appearance and deep duodenoscopy make the diagnosis easy. Volvulus in
      cases of malrotation, Ladd's ligaments, annular pancreas, and compression of the
      duodenum by mesenteric vessels must be considered in the differential diagnosis.
      When the intraduodenal membrane is resected it is most important to expose the
      papilla Vateri, since this not uncommonly ends in the area of the septum. If
      necessary, a duodenoduodenostomy is performed. If the windsock web abnormality is
      present the duodenum should be opened at the point of attachment of the
      diaphragm. The construction of a gastrojejunostomy should be avoided.

PMID- 8145620
TI  - Donor criteria in hepatic transplantation.
AB  - The early outcome of 201 liver grafts transplanted consecutively between
      September 1988 and November 1991 was investigated retrospectively. Donors were
      categorized according to their hospitalization periods in an intensive care unit
      (ICU) prior to harvesting, their causes of death, and the variables generally
      believed to be critical in liver donation, such as arterial hypotension (n = 69;
      34.3%), cardiopulmonary resuscitation (n = 20; 9.9%), elevated serum
      aminotransferases (s-AT) (n = 11; 5.5%), or an age over 50 years (n = 16; 8.0%).
      Ninety-one donors (45.3%) spent less than 24 h in an ICU; 29 donors (14.4%) and
      14 donors (7.0%) had hospitalization periods generally considered critical of 4-6
      days and more than 6 days, respectively. The most common causes of death were
      subarachnoidal bleeding (n = 70; 34.8%), isolated head injuries (n = 68; 33.8%),
      and polytraumata (n = 33; 16.4%). The postischemic hepatocellular damage was
      evaluated comparing peak post-transplant s-AT, which did not differ significantly
      between groups; nor did donor and recipient ages or cold ischemia times. Fourteen
      grafts (7.0%) showed a reversible preservation injury presenting with post
      transplant s-AT elevated above 2000 IU/l. Five cases (2.5%) of a primary non
      functioning graft (PNF) underwent early retransplantation successfully. Serum
      aminotransferases (AST: 4944 +/- 2280 IU/l; ATL: 3186 +/- 1918 IU/l) were
      significantly (P < 0.01) elevated as compared to primary functioning grafts (AST:
      699 +/- 935 IU/l; ALT: 620 +/- 701 IU/l). The donor structure of both groups
      reflected the distribution of variables in the entire collective. No significant
      overrepresentations were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145621
TI  - [Correlation between pulmonary hypertension and portal hypertension--2 case
      reports of different forms of pre-sinusoidal portal hypertension].
AB  - Since its first description in 1951 by Mantz and Craig pulmonary hypertension in
      combination with portal hypertension has been observed more and more frequently.
      In a recent prospective study Hadengue et al. reported an incidence of 2%. Thus
      this simultaneous occurrence can no longer be considered to be coincidental. The
      etiology remains still unclear. It is most probable that the development is due
      to vasoactive substances which bypass the liver or which are produced in the lung
      itself, and which, due to a long-term vasoconstriction, causes irreparable damage
      to the arterioles and arteries in the lung. Such pulmonary hypertension can
      develop in the presence of a pre- as well as an intrahepatic block, even when the
      portal hypertension is partially or completely alleviated by a portosystemic
      anastomosis. This last circumstance can be illustrated by two cases which were
      observed by our group. Case A is of particular interest because it is the first
      documentation of a case of an intrahepatic block due to a (so-called)
      macronodular transformation of the liver in the absence of portal thrombosis (a
      so-called NRH: nodular regenerative hyperplasia) in combination with pulmonary
      hypertension. This type of non-cirrhotic portal hypertension can be associated
      with micronodular transformation of the liver as well. Post-hepatic blocks or the
      so-called BUDD-CHIARI Syndrome type appear to carry no risk of development of
      pulmonary hypertension. It remains unclear which particular etiologies increase
      susceptibility to later development of pulmonary hypertension.

PMID- 8145622
TI  - [Value of sonography in routine diagnosis of acute appendicitis. A retrospective
      analysis].
AB  - Our retrospective study of ultrasound examinations in 261 consecutively
      appendectomized patients shows a lower sensitivity in sonographic diagnosis of
      acute appendicitis compared to our former prospective study. One reason seems to
      be the different experience of the participating surgeons in ultrasound
      examination of acute appendicitis. Conditions of a prospective study might be
      another reason for our former better results. In conclusion recognition of
      appendicitis during ultrasound must lead to early operation, but a negative
      ultrasound alone is not safe enough to avoid surgical intervention in clinically
      supposed appendicitis. In every-day surgery clinical experience combined with
      additionally performed ultrasound leads to an early and safe indication for
      appendectomy.

PMID- 8145623
TI  - [Osteopenia in chronic inflammatory bowel diseases. Results of a cross-sectional
      study using quantitative computerized tomography].
AB  - 53 unselected patients with Crohn's disease (CD) (35 female, 18 men; mean age:
      32.3 +/- 12.5 y.; mean duration of CD: 78.6 +/- 65.7 months) and 23 patients with
      ulcerative colitis (UC) (8 female, 15 men; mean age: 43.7 +/- 17.9 y.; mean
      duration of UC: 100.7 +/- 86.0 months) were examined by quantitative
      computertomography (lumbar spine 1-3). Incipient (manifest) osteopenia (OP) was
      defined as a reduced axial bone mineral density from -1 standard deviations (SD)
      to -2 (SD) (< -2SD) as compared to a control Group. Reduced bone mineral density
      was found in 30.2% (16/53) of patients with CD and 9% (2/23) with UC (p < 0.05).
      In particular 12/53 pts. (22.6%) with CD and 1/23 pts. (4.35%) with UC showed
      incipient OP, whereas 4/53 pts. (7.5%) with CD and 1/23 pts. (4.35%) with UC
      showed manifest OP. With respect to the location of CD the mean relative bone
      density (SD) was found to be significantly lower in patients with ileal
      involvement of CD (-0.88 +/- 0.8 SD; n = 39) as compared to patients with colonic
      involvement (-0.09 +/- 0.86 SD; n = 14) and UC (-0.09 +/- 0.55 SD; n = 23) (p <
      0.05). No significant correlation to the duration of the disease was found.
      Previous therapy with steroids led to lower mineral bone density as compared to
      untreated patients. As a trend duration of steroid treatment and bone density
      were shown to be correlated inversely.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145624
TI  - [Alpha-heavy chain disease--Mediterranean lymphoma].
AB  - For 6 months diarrhea and weight loss of 30 kg occurred in a 28 year old man from
      the Emirates. The endoscopic examination suggested a small intestinal lymphoma
      affecting the entire small intestine, which was confirmed by biopsies,
      immunohistochemistry, immunologic proof of monoclonal IgA-gammopathy in serum and
      urine. The patient acquired a malignant MALT-lymphoma of B-cell-type, a alpha
      Heavy Chain Disease, synonym mediterranean lymphoma or immunoproliferative small
      intestinal disease (IPSID), stage A with transition in stage B. The patient was
      treated with ciprofloxacine in association with metronidazole with no influence
      of the course of the disease.

PMID- 8145625
TI  - [Fatal subileus caused by intestinal amyloidosis in light chain plasmacytoma].
AB  - This report concerns a patient with systemic amyloidosis due to a plasmocytoma,
      in whom massive amyloid depositions in the small bowel caused severe diarrhoea
      and malabsorption. The excessive amyloid depositions in the lamina muscularis
      propria of the bowel finally resulted in therapy-resistant motility disturbance
      and adynamic subileus with fatal outcome.

PMID- 8145626
TI  - [Echinococcosis--current status of diagnosis and therapy].

PMID- 8145627
TI  - [Echinococcosis--current status of diagnosis and therapy].

PMID- 8145628
TI  - [Current therapy of Helicobacter pylori infection].

PMID- 8145629
TI  - Collaboration in clinical computing at LDS Hospital.

PMID- 8145630
TI  - Computer-assisted instruction: from clinic to classroom.

PMID- 8145631
TI  - Word processors for the Macintosh: a comparison of five programs.

PMID- 8145632
TI  - Computer interview for screening blood donors for risk of HIV transmission.
AB  - To test the ability of a computer-based interview to detect factors related to
      the risk of the human immunodeficiency virus (HIV) among potential blood donors,
      and to determine donor reactions to the use of the computer, we compared the rate
      of detection of HIV-related factors elicited by the computer interview with the
      rate elicited by standard American Red Cross procedures (written questionnaires
      and face-to-face interviews) for assessment of donor suitability. The study was
      performed at a Red Cross blood donor center and a hospital. A consecutive sample
      of 294 male and female blood donors 18 to 75 years of age participated in a
      randomized crossover trial in which the order of the two methods was reversed.
      Among 272 prospective donors who provided complete data, the computer identified
      12 who reported either behavior associated with a risk of acquiring HIV or
      symptoms compatible with AIDS. None of these 12 was so identified by face-to-face
      interviews or written questionnaires. Only one used the confidential unit
      exclusion procedure to prevent use of his donated blood. Tests for antibody to
      HIV were negative in blood from all 272 subjects. The subjects enjoyed the
      computer interview and judged it to be more private than the standard method for
      donor assessment.

PMID- 8145633
TI  - Brain processing of optical input: the perception of visual reality.

PMID- 8145634
TI  - The delivery of medical care. 1970.

PMID- 8145635
TI  - Transfer of laboratory data from a mainframe to a microcomputer: an interim
      approach.

PMID- 8145636
TI  - Sidney R. Garfield and the crisis in health care.

PMID- 8145637
TI  - Physician order entry.

PMID- 8145638
TI  - Clonal spread of serogroup A meningococci: a paradigm for the analysis of
      microevolution in bacteria.
AB  - Extensive epidemiological analyses of epidemics of meningococcal meningitis have
      resulted in large, well-defined strain collections which represent the local
      diversity and global spread of serogroup A bacteria. Several genes for cell
      surface proteins are conserved during spread, with a few exceptions: analysis of
      these exceptions has revealed some of the phenomena which can lead to
      microevolution. Microevolution is so rapid with serogroup A meningococci that
      several independent recombination events have been documented within the last few
      decades. In a few cases, the recombinant bacteria have become established by
      clonal replacement plus epidemic spread. Comparison with other bacteria indicates
      that serogroup A meningococci provide a number of advantages for analysis of
      microevolution.

PMID- 8145639
TI  - Structure and heterologous expression of the Ustilago maydis viral toxin KP4.
AB  - Killer toxins are polypeptides secreted by some fungal species that kill
      sensitive cells of the same or related species. In the best-characterized cases,
      they function by creating new pores in the cell membrane and disrupting ion
      fluxes. Immunity or resistance to the toxins is conferred by the preprotoxins (or
      products thereof) or by nuclear resistance genes. In several cases, the toxins
      are encoded by one or more genomic segments of resident double-stranded RNA
      viruses. The known toxins are composed of one to three polypeptides, usually
      present as multimers. We have further characterized the KP4 killer toxin from the
      maize smut fungus Ustilago maydis. This toxin is also encoded by a single viral
      double-stranded RNA but differs from other known killer toxins in several
      respects: it has no N-linked glycosylation either in the precursor or in the
      mature polypeptide, it is the first killer toxin demonstrated to be a single
      polypeptide, and it is not processed by any of the known secretory proteinases
      (other than the signal peptidase). It is efficiently expressed in a heterologous
      fungal system.

PMID- 8145640
TI  - Genetic characterization of a Rhizobium meliloti lactose utilization locus.
AB  - We identified several linked genes of a lactose regulon in Rhizobium meliloti.
      These were lacZ, the structural gene for beta-galactosidase; lacR, the lactose
      repressor gene; and two genes encoding proteins of unknown function, lacW and
      lacX. Insertion mutants in lacW and lacZ belonged to a single genetic
      complementation group, and lacW appeared to lie upstream of lacZ in an operon.
      Expression of lacZ, lacW and lacX was repressed by lacR, and expression of lacZ
      and lacW was derepressed by lactose. lacZ was not required for induction of lacW
      by lactose, suggesting that lactose itself, rather than a processed form of
      lactose, may be the actual inducer molecule. Expression of all three genes was
      repressed by succinate, and the lacR independence of this repression showed that
      inducer exclusion could not be the sole mechanism. This pattern of lac gene
      organization and regulation differs in several ways from that observed in enteric
      bacteria.

PMID- 8145641
TI  - Glycogen in Bacillus subtilis: molecular characterization of an operon encoding
      enzymes involved in glycogen biosynthesis and degradation.
AB  - Although it has never been reported that Bacillus subtilis is capable of
      accumulating glycogen, we have isolated a region from the chromosome of B.
      subtilis containing a glycogen operon. The operon is located directly downstream
      from trnB, which maps at 275 degrees on the B. subtilis chromosome. It encodes
      five polypeptides with extensive similarity to enzymes involved in glycogen and
      starch metabolism in both prokaryotes and eukaryotes. The operon is presumably
      expressed by an E sigma E-controlled promoter, which was previously identified
      downstream from trnB. We have observed glycogen biosynthesis in B. subtilis
      exclusively on media containing carbon sources that allow efficient sporulation.
      Sporulation-independent synthesis of glycogen occurred after integration of an E
      sigma A controlled promoter upstream of the operon.

PMID- 8145642
TI  - Homologous pairing proteins encoded by the Escherichia coli recE and recT genes.
AB  - Early genetic analysis of alternate recombination pathways in Escherichia coli
      identified the RecE recombination pathway and the required exonuclease VIII
      encoded by the recE gene. Observations that not all recombination events promoted
      by the RecE pathway require recA suggest the existence of an additional
      homologous pairing protein besides RecA in E. coli. Genetic and biochemical
      analysis of the recE gene region indicates there are two partially overlapping
      genes, recE and recT, encoding at least two proteins: exoVIII and the RecT
      protein. Biochemical analysis has shown that the RecT protein, in combination
      with exoVIII, promotes homologous pairing and strand exchange in reactions
      containing linear duplex DNA and homologous, circular, singlestranded DNA as
      substrates. This reaction occurs in the absence of any high-energy cofactor.
      These two proteins, RecT and exoVIII, appear to be members of a second class of
      homologous pairing proteins that are required in genetic recombination and differ
      from the class of homologous pairing proteins that includes RecA. Members of this
      second class of proteins appear to include both bacteriophage-encoded proteins
      and proteins from eukaryotes and their viruses.

PMID- 8145643
TI  - Regulatory implications of translational frameshifting in cellular gene
      expression.
AB  - The genetic code, once thought to be rigid, has been found to be quite flexible,
      permitting several different reading alternatives. One of these is translational
      frameshifting, a process programmed in the mRNA sequence and which enables a +1
      or -1 shift from the reading frame of the initiation codon. So far, the
      involvement of translational frameshifting in gene expression has been described
      mainly in viruses (particularly retroviruses), retrotransposons, and bacterial
      insertion elements. In this MicroReview, we present a survey of the cellular
      genes, mostly in Escherichia coli, which have been found to be expressed through
      a translational frameshifting process, as well as a discussion of the regulatory
      implications of this process.

PMID- 8145644
TI  - Identification and characterization of a chromosomal virulence gene, vacJ,
      required for intercellular spreading of Shigella flexneri.
AB  - Intercellular spreading of shigellae is a prerequisite for shigellosis, although
      the molecular mechanisms underlying the phenomenon are still largely obscure. To
      elucidate some of these mechanisms, we performed random Tn10 insertion
      mutagenesis in Shigella flexneri YSH6000T and found a chromosomal locus in the
      NotI-J segment responsible for bacterial spreading. The locus affected in the
      mutant, designated vacJ, was neither involved in the invasion of epithelial cells
      nor in intracellular movement, but was required for intercellular spread. The
      vacJ mutant was capable of forming bacterium-containing membranous protrusions
      within the infected cell, but had diminished ability to move from the protrusions
      into the cytoplasm of the adjacent epithelial cells. Cloning and sequencing of
      the vacJ region indicated that the vacJ gene encoded a 28.0 kDa protein
      possessing a signal peptide at the N-terminus, which contained the motif
      characteristic of lipoproteins. The analysis of the vacJ product indicated that
      VacJ was exposed on the bacterial surface. The vacJ gene was distributed among
      shigellae and enteroinvasive Escherichia coli, and the constructed vacJ mutants
      failed to spread intercellularly, indicating that vacJ is a chromosomal gene
      essential for the pathogenicity of shigellae.

PMID- 8145645
TI  - Topology of diphtheria toxin B fragment inserted in lipid vesicles.
AB  - Diphtheria toxin (DT) is a bacterial protein that crosses the membrane of
      endosomes of target cells in response to the low endosomal pH. In this paper, we
      have inserted diphtheria toxin in asolectin vesicles at pH 5.0 and treated the
      reconstituted system with pronase. The peptides that were protected from
      digestion were separated by gel electrophoresis, transferred to a membrane and
      their N-terminal sequences were determined. All peptides belong to the B fragment
      of DT and cover residues 194-223, 265-375 and 429-528. The secondary structures
      of the peptides inserted in the membrane, determined by Fourier-transformed
      infrared spectroscopy, were shown to be mostly alpha-helices and beta-sheets (44%
      and 53%, respectively). On the basis of these data and the recently published X
      ray structure of DT, we are proposing a topology for the DTB fragment in the
      membrane.

PMID- 8145646
TI  - Structure and expression of the alternative sigma factor, RpoN, in Rhodobacter
      capsulatus; physiological relevance of an autoactivated nifU2-rpoN superoperon.
AB  - The alternative sigma factor, RpoN (sigma 54) is responsible for recruiting core
      RNA polymerase to the promoters of genes required for diverse physiological
      functions in a variety of eubacterial species. The RpoN protein in Rhodobacter
      capsulatus is a putative sigma factor specific for nitrogen fixation (nif) genes.
      Insertional mutagenesis was used to define regions important for the function of
      the R. capsulatus RpoN protein. Insertions of four amino acids in the predicted
      helixturn-helix or in the highly conserved C-terminal eight amino acid residues
      (previously termed the RpoN box), and an in-frame deletion of the glutamine-rich
      N-terminus completely inactivated the R. capsulatus RpoN protein. Two separate
      insertions in the second hydrophobic heptad repeat, a putative leucine zipper,
      resulted in a partially functional RpoN protein. Eight other linkers in the rpoN
      open reading frame (ORF) resulted in a completely or partially functional RpoN
      protein. The rpoN gene in R. capsulatus is downstream from the nifHDKU2 genes, in
      a nifU2-rpoN operon. Results of genetic experiments on the nifU2-rpoN locus show
      that the rpoN gene is organized in a nifU2-rpoN superoperon. A primary promoter
      directly upstream of the rpoN ORF is responsible for the initial expression of
      rpoN. Deletion analysis and insertional mutagenesis were used to define the
      primary promoter to 50 bp, between 37 and 87 nucleotides upstream of the
      predicted rpoN translational start site. This primary promoter is expressed
      constitutively with respect to nitrogen, and it is necessary and sufficient for
      growth under nitrogen-limiting conditions typically used in the laboratory. A
      secondary promoter upstream of nifU2 is autoactivated by RpoN and NifA to
      increase the expression of rpoN, which ultimately results in higher expression of
      RpoN-dependent genes. Moreover, rpoN expression from this secondary promoter is
      physiologically beneficial under certain stressful conditions, such as nitrogen
      limiting environments that contain high salt (> 50 mM NaCl) or low iron (< 400 nM
      FeSO4).

PMID- 8145648
TI  - A new class of proteins regulating gene expression in enterobacteria.
AB  - YmoA and Hha are highly similar bacterial proteins downregulating gene expression
      in Yersinia enterocolitica and Escherichia coli, respectively. The phenotype of
      ymoA mutants evokes that of mutants affected in some histone-like proteins. This
      paper describes complementation of a ymoA mutation in Y. enterocolitica by the
      hha gene from E. coli. We show that YmoA and Hha are not only very similar
      proteins but that they are functionally interchangeable. Genetic experiments
      indicate that Hha can also stimulate transposition events in vivo. By Southern
      blot analysis we detected hha-homologous genes at least in Citrobacter diversus,
      Shigella flexneri, Shigella dysenteriae, Klebsiella pneumoniae and Salmonella
      typhimurium. We suggest that both YmoA and Hha belong to a new family of proteins
      downregulating gene expression in different enterobacteria.

PMID- 8145647
TI  - Molecular analysis of the Erwinia chrysanthemi region containing the kdgA and zwf
      genes.
AB  - The pathways of pectin and galacturonate catabolism in Erwinia chrysanthemi
      converge to form a common intermediate, 2-keto-3-deoxygluconate, which is
      phosphorylated to form 2-keto-3-deoxy-6-phosphogluconate (KDGP) and then cleaved
      by the aldolase encoded by the kdgA gene. We cloned the kdgA gene of the E.
      chrysanthemi strain 3937 by complementing an Escherichia coli kdgA mutation,
      using an RP4-derivative plasmid. Restriction mapping of the kdgA region and
      isolation of kdgA-lac fusions allowed the more precise localization of the kdgA
      gene and determination of its transcriptional direction. The nucleotide sequence
      of the kdgA region indicated that the kdgA reading frame is 639 bases long,
      corresponding to a protein of 213 amino acids with a molecular mass of 22,187 Da.
      Comparison of the deduced primary amino acid sequences of the E. chrysanthemi
      KDGP-aldolase to the E. coli, Zymomonas mobilis and Pseudomonas putida enzymes
      showed that they are highly conserved. The E. chrysanthemi kdgA structural gene
      begins 153 bases downstream of an open reading frame that has a high homology
      with the zwf E. coli gene encoding glucose-6-phosphate dehydrogenase. The zwf
      gene is also linked to eda (kdgA) in E. coli and P. putida but genetic
      organization is different. Regulation of zwf and kdgA expression in E.
      chrysanthemi was analysed using lacZ fusions. The expression of zwf is
      independent of the growth rate, but is repressed in the presence of glucose.
      Induction of kdgA by pectin-degradation products is mediated in vivo by the
      negative regulatory gene kdgR, which also controls all the steps of pectin
      degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145649
TI  - Mammalian and Escherichia coli signal recognition particles.
AB  - Recent evidence from both biochemical and genetic studies indicates that protein
      targeting to the prokaryotic cytoplasmic membrane and the eukaryotic endoplasmic
      reticulum membrane may have more in common than previously thought. A
      ribonucleoprotein particle was identified in Escherichia coli that consists of at
      least one protein (P48 or Ffh) and one RNA molecule (4.5S RNA), both of which
      exhibit strong sequence similarity with constituents of the mammalian signal
      recognition particle (SRP). Like the mammalian SRP, the E. coli SRP binds
      specifically to the signal sequence of presecretory proteins. Depletion of either
      P48 or 4.5S RNA affects translation and results in the accumulation of precursors
      of several secreted proteins. This review discusses the recent studies and
      speculates on the position of the SRP in the complex network of protein
      interactions involved in translation and membrane targeting in E. coli.

PMID- 8145650
TI  - Evidence that residues -15 to -46 of the haemolysin secretion signal are involved
      in early steps in secretion, leading to recognition of the translocator.
AB  - We previously identified three well-dispersed mutations, E978-K, F989-L and D1009
      R within the haemolysin A signal region, located at positions -46, -35 and -15,
      with respect to the C-terminus, respectively. Each mutation reduces the
      efficiency of secretion two- to threefold leaving 30-45% of the wild-type
      activity. We have constructed by in vitro manipulations double mutants of HlyA
      carrying all combinations of these mutations and a triple mutant carrying all
      three mutations. The effects on secretion were determined and the results,
      including residual levels of secretion with the triple mutant of only 0.6%,
      compared with the wild type, indicated that these residues may interact to form a
      single function in the wild-type signal. To test this further, we developed a
      secretion competition assay in order to classify signal mutations. We
      demonstrated that a CIZ-HlyA fusion protein, containing the C-terminal 81 kDa of
      HlyA fused to virtually the whole LacZ protein, strongly inhibits the secretion
      of the wild-type HlyA co-expressed in the same cell. The properties of the fusion
      indicate that it blocks the translocator. The three mutations singly and in
      combinations were recombined in vitro into the 3'-end of the hybrid gene. In
      every case, the presence of a mutation in the secretion signal of the hybrid
      protein alleviated the inhibition of secretion of the co-expressed HlyA. All the
      mutations are therefore essentially recessive and we propose that they all affect
      an early function, probably recognition of the translocator, rather than a
      subsequent step involved in translocation or final release of the toxin to the
      medium. This would indicate that residues involved in recognition (or steps
      leading to recognition) extend from at least -15 to -46 with respect to the HlyA
      C-terminus.

PMID- 8145651
TI  - The 'cerebral diabetes' paradigm for unipolar depression.
AB  - Unipolar depression, alcoholism and suicide have become more common over the past
      decades. Genetic studies have attempted to link (bipolar) affective disorder to
      the short arm of chromosome 11 (where the loci for insulin, insulin growth factor
      (IGF), tyrosine hydroxylase (TH) and h-ras-oncogene are located) but these have
      failed. Since TH and the insulin receptor require phosphorylation by protein
      kinases, then a defect of the h-ras-oncogene or its products (p21) could disorder
      both these systems and compromise catecholaminergic transmission in neurones and
      energy flow in glial cells. This could lead not only to a predisposition to
      depression ('trait markers') but to neurotoxic damage, predisposed by inadequate
      cytosol Mg2+ levels of hypometabolism. Tyrosine, tryptophan and phenylalanine
      hydroxylases all require tetrahydrobiopterin (BH4) which allosterically regulates
      its own activity as well as that of these enzymes. Anything which impairs this
      cofactor could lead to overt depression in predisposed individuals, and the
      heterocyclic amines are being increasingly implicated. These substances are
      derived from fried and broiled meats, azo food dyes, soft drinks and hard
      candies, but particularly from cigarette and petroleum fumes. The heterocyclic
      amines can inhibit aromatic-l-amino-acid-decarboxylase (AADC) as well as the
      hydroxylases reversibly, but BH4 is inhibited noncompetitively. Thus, susceptible
      individuals (those with inherited defective protein kinase phosphorylation) might
      be 'tipped over' by chronic exposure to these neurotoxins. The rising incidence
      of unipolar depression-associated morbidity could be significantly linked to
      increasing levels of heterocyclic amines in the developed nations.

PMID- 8145652
TI  - Further comments on the evolutionary origin of the mammalian brain.
AB  - This paper is an extension of a previous report on the origin of the mammalian
      neocortex. Two main aspects are elaborated. The first is the evolution of visual
      projections from the midbrain to the telencephalon, featuring the encephalization
      of visual functions. Associated to this, the progressive fusion of the two main
      visual systems (thalamofugal and tectofugal) in the mammalian telencephalon
      (striate and extrastriate cortex, respectively) is viewed in the context of
      increasing cortico-cortical connectivity in the evolution of the mammalian brain.
      In addition, the issue of a presumed homology between mammalian extrastriate
      cortex and reptilian anterior dorsal ventricular ridge (ADVR) is reviewed in some
      detail, and it is concluded that extrastriate cortex is a derived character of
      mammals while ADVR is a derived character of reptiles and birds. It is not likely
      that ADVR is ancestral to extrastriate cortex. The second aspect under analysis
      is the origin of the inverted (inside-out) lamination pattern of mammalian
      neocortex that differs from the outside-in pattern of reptilian cortex.
      Furthermore, mammals have developed a transient embryonic cell layer (the
      subplate zone) that serves as a waiting compartment for thalamic and cortico
      cortical axons while their prospective target cells end their migration process
      to reach their final positions. It is postulated that both, inverted lamination
      and the subplate zone arose in evolution as successive and complementary
      strategies to maximize synaptic contacts between thalamic afferents and the new
      cortical cell types (belonging to prospective granular and supragranular layers)
      that were being originated at that moment.

PMID- 8145653
TI  - Is raised von Willebrand factor a marker of endothelial cell damage?
AB  - This hypothesis proposes that, in the absence of actively metastasising
      neoplasia, damage to the endothelium can be monitored by measuring circulating
      levels of von Willebrand factor. This specific product of the endothelial cell is
      important in thrombo-genesis as its functions include platelet aggregation and
      mediation of platelet adhesion to the subendothelium. High levels are found in
      all major risk factors of atherosclerosis, in frank atherosclerotic vascular
      disease and in most of the inflammatory vasculitides, and the highest levels are
      also associated with more severe disease and risk of mortality. It follows that
      high levels of von Willebrand factor may be a new risk factor for the development
      of thrombosis and atherosclerosis.

PMID- 8145654
TI  - The storage of energy as a cause of malignant transformation: a 7-phase model of
      carcinogenesis.
AB  - Although many theories for the development of cancer exist, a new hypothesis for
      carcinogenesis is suggested and a new 7-phase model of malignant transformation
      described. Both the hypothesis and the model are based on the principle of a
      critical point in local energy (entropy?) storage, at a certain level of
      structural organisation within the cells. This principle has been previously
      formulated by the author from the rules of non-equilibrium thermodynamics. The
      model introduces a new terminology and explores the concepts of both high work
      value of energy and bifurcation. The ability (A) of cells is suggested to be the
      most important cellular feature in respect to cell survival. This ability implies
      that the cells follow the requirement Kir > 1, even in dangerous situations and
      under harmful environmental influence. But, when the cells have lost their
      ability (A) and all levels of the cell defence machine have been exhausted, then
      the local energy storage may provoke a cascade of harmful events within the
      cells. The S-stage is the most unstable state of the cell cycle. If such harmful
      events take place during DNA synthesis within the 'premalignant' cell, in the
      phase 'promotion' at the 4th bifurcation, they lead ultimately to carcinogenesis
      (i.e. malignant transformation). The 7-phase model of carcinogenesis is
      consistent and offers many advantages in comparison to the previous hypotheses.
      This model could help the design of experiments, development of new drugs and
      optimization of medical treatment. The new hypothesis could contribute to a
      better understanding of the processes of carcinogenesis and the uncontrolled
      division, growth and lability of tumour cells.

PMID- 8145655
TI  - Is Alzheimer's disease related to a deficit or malfunction of rapid eye movement
      (REM) sleep?
AB  - Current theories of the cause of Alzheimer's disease (AD) do not address the
      question as to why AD patients initially and gradually lose their short-term
      memory, followed later by progressive and accelerated loss of other memory,
      language, motor skills, perception and very short-term memory. We propose that
      this pattern of memory loss may be a result of a REM sleep deficit or
      malfunction. This hypothesis is also supported by: 1) Results which show that AD
      patients have less REM sleep than controls. 2) There is an established close
      correspondence between learning/memory and REM sleep. REM sleep deprivation is
      known to result in impairment in learning recent information. 3) AD patients have
      a degenerated cholinergic system of the brain. The cholinergic system is known to
      activate/stimulate the REM sleep process. 4) The lesions in AD victims are
      primarily located in those regions of the brain that are considered to be active
      during REM sleep. 5) There is a natural mechanism by which the REM sleep in
      humans is reduced from 8 hours each day at birth to less than 1 hour each day in
      old age. An acceleration of this process can lead to possible REM deficit at old
      age. Furthermore, since old people have so little REM sleep they are more
      vulnerable to a REM sleep deficit. The REM sleep deficit mechanism may also work
      in conjunction with other theories of the etiology of AD, in which case, the REM
      sleep deficit may explain the progression and/or the acceleration of memory loss
      in AD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145656
TI  - Abrogation of facial seborrhoeic dermatitis with homoeopathic high dilutions of
      tobacco: a new visible model for Benveniste's theory of 'Memory of water'.
AB  - The author describes the activity of homoeopathic high dilutions of tobacco to
      treat his familial facial seborrhoeic dermatitis induced by the hapten nicotine.
      A double-blind experiment against placebo and several treatments with continuous
      and single intakes of tobacco high dilutions led after a break to a late
      abrogation of dermatitis simulating a desensitization. These observations provide
      a new possible explanation for the placebo effect and facial seborrhoeic
      dermatitis is proposed as a new visible model for Benveniste's theory of 'Memory
      of water'.

PMID- 8145657
TI  - Is primary open angle glaucoma caused by small proteins?
AB  - Primary open angle glaucoma is a disease which is characterized by a decreased
      facility of outflow of aqueous humor from the anterior segment of the eye.
      Analyses by gel exclusion chromatography of the aqueous humor of normal monkeys
      have shown that the proteins in this fluid range in size from approximately 40
      200 kilodaltons. Although small proteins and peptides are seen in the aqueous
      humor by SDS gel electrophoresis, these smaller proteins appear to elute by
      column chromatography with the albumin peak. In the outflow of the aqueous humor,
      the trabecular meshwork may be an efficient sieve for proteins of intermediate
      size, but this tissue may be obstructed if the proteins present become too large
      or too small as a result of other disease processes in the eye. Primary open
      angle glaucoma may be the result of the inability of the trabecular meshwork to
      filter small proteins and polypeptides efficiently.

PMID- 8145658
TI  - Marital status and timing of coronary artery surgery.
AB  - Women undergoing surgery for coronary artery disease are older and have greater
      impairment of functional status than their male counterparts, suggesting either
      gender differences or gender bias. Reduced willingness to accept risks of surgery
      and reduced reliability of non-invasive tests in women have been proposed as
      possible explanations of surgical intervention delay. Since women survive their
      husbands by 7 years, their role as a terminal caretaker may impede acceptance of
      recommended surgery. In a record review of 145 women who underwent coronary
      artery bypass surgery, widows, as compared with the general population, were over
      represented in each of the 3 decades from age 45-74. A prospective study to
      assess the several variables contributing to poorer surgical outcome in women is
      warranted.

PMID- 8145659
TI  - The production of short-chain fatty acids by periodontopathic bacteria
      contributes to the impairment of local host defence.

PMID- 8145660
TI  - Does excessive television viewing contribute to the development of dementia?
AB  - The etiology of most kinds of dementia is still obscure and is probably
      multifactorial. We query whether excessive watching of television may contribute
      to the development of dementive processes for the following reasons: TV
      spectators are exposed to a mass of successive and rapid stimuli with little or
      no possibility of relating to the viewing matter. In addition, a considerable
      part of the material is stressogenic, and generally there is no opportunity for a
      subsequent release of tension. Stress, via the glucocorticosteroids which it
      induces, has been shown to damage neurons in the hippocampus, a brain region
      involved in memory processes. Considering that many individuals have by now been
      watching television for several decades, not infrequently at an average rate of 4
      or more hours daily, it is possible that cumulative, stress-derived damage may
      magnify the risk of a dementive process in such long-term, habitual viewers. Upon
      clinical intake of cases of suspected dementia, it is suggested that inquiry into
      the patient's television watching habits be incorporated into the anamnesis.

PMID- 8145661
TI  - On the mechanism of HIV disease: a hypothesis and the anti-AIDS therapy it
      suggests.
AB  - A hypothesis is proposed interpreting transformation of the asymptomatic (latent)
      phase of HIV disease into full-blown AIDS. According to the hypothesis, AIDS in
      an HIV infected individual is caused by just that HIV strain which fits host's
      genotype in that way preventing production of the antibody specific to that
      strain. The strain appears at random time as a result of the antigenic drift that
      takes place during the latent phase of HIV disease. If the strain is transmitted
      to another individual, the new host produces the strain-specific antibodies
      resulting in successful suppression of the strain, specific to the genotype of
      just the first host. The idea of the treatment, suggested by the hypothesis,
      consists of the use of the strain-specific antibodies produced by the second
      individual for suppressing the genotype-specific strain killing the first
      individual (and vice versa). One of the consequences following from the
      hypothesis, is the physical impossibility of an AIDS preventive vaccine.

PMID- 8145662
TI  - Thymus-neuroendocrine-liver pathway.
AB  - In order to investigate the influence of the thymus on liver functions, we used
      adult thymectomized rats as a model and supplemented the animals with either
      thymic extracts or sex hormones. Male thymectomized rats exhibited a decrease in
      liver microsomal cytochrome P-450 and aminopyrine-N-demethylase activities. There
      was also a decrease in the levels of hypothalamic luteinizing hormone-releasing
      hormone (LHRH), plasma luteinizing hormone (LH) and testosterone. Supplementation
      of testosterone propionate to these animals restored their liver P-450 and
      demethylase activities to normal levels. Female thymectomized rats showed an
      increase of liver malondialdehyde (MDA), accompanied by a decrease of liver
      superoxide dismutase (SOD) and glutathione (GSH), and a decline of fluidity and
      calcium ion uptake in liver microsomal and mitochondrial membranes. There was
      also a decline in hypothalamic LHRH and plasma estradiol. Supplementation of
      thymic extract to female thymectomized rats decreased the liver MDA, increased
      the liver GSH, and restored the microsomal and mitochondrial membrane fluidity
      and calcium ion uptake. The decrease of liver MDA was also achieved by
      administration of estradiol benzoate. The data suggest that the thymus may
      influence liver functions through the hypothalamus-pituitary-gonad axis. Thus, a
      new 'thymus-neuroendocrine-liver pathway' is proposed that further affirms the
      significance of the thymus on maintaining homeostasis and integrative functions
      in the body.

PMID- 8145664
TI  - [Signal transduction by G-proteins].

PMID- 8145663
TI  - Radiation and aging: free radical damage, biological response and possible
      antioxidant intervention.
AB  - In this review, the basic processes responsible for radiation-induced changes in
      critical cell components and their biological consequences will be discussed. The
      chemical and physical alterations in biomolecules are mediated by free radicals
      and other reactive intermediates formed, following absorption of radiant energy,
      by ionization of proximal targets or the surrounding water molecules.
      Accumulation of free radical damage and its catalysis by various oxidants
      including quinones and other age pigments, metal ions, lipid peroxides,
      prostaglandins and components released from cells, increase with age. A cell's
      response to such damage depends upon environmental and inherited factors. DNA
      repair is an effective way to protect against radiation damage, but other
      constitutive or inducible defence mechanisms can also modify biological response,
      and these processes generally become less effective with age. Loss of fidelity
      with age of bio-feedback mechanisms including homeostasis, redox control, ion and
      metabolic regulation, which in turn affects cell growth and differentiation,
      energy efficiency, the immune system and general health, can be associated with
      free radical pathology. Current theories of aging will be examined including
      those involving wear-and-tear, genetic, metabolic, immunologic and biochemical
      factors. Ionizing radiation, as with other external stresses including UV, heat,
      chemotherapeutic agents, chemical carcinogens and tumor promoters, interact with
      nucleic acids, proteins and membrane phospholipids facilitating free radical
      mediated oxidative damage. Appropriate antioxidant intervention, by inhibiting or
      reducing free radical toxicity, may offer protection against radiation, and
      alleviate or delay symptoms of aging and chronic disease.

PMID- 8145665
TI  - [Tick-borne infections. Detection, diagnosis, therapy and prevention].

PMID- 8145666
TI  - [Drug-induced polyneuropathies].

PMID- 8145667
TI  - Forensic medicine.

PMID- 8145668
TI  - Ethics and the public health.

PMID- 8145669
TI  - Radiation, Chernobyl and the media.

PMID- 8145670
TI  - A little learning....

PMID- 8145671
TI  - Medical review committees and privilege in the USA.

PMID- 8145672
TI  - Aerosolized deoxyribonuclease for cystic fibrosis.

PMID- 8145673
TI  - [Follow-up and social consequences of Crohn disease and ulcerative colitis].
AB  - PATIENTS: We studied the course and particularly the social consequences of
      Crohn's disease (n = 107) and ulcerative colitis extending beyond the sigmoid
      colon (n = 22) during the first 6.1 respectively 6.3 years after onset. RESULTS:
      Under common treatment, the disease activity decreased and the body mass index
      increased significantly in the majority of patients, but about 30% of them
      reached no continuous remission. The professional training was delayed in 23% of
      patients with Crohn's disease and 9% of those with ulcerative colitis. However,
      by objective datas and in the patients' own opinion the effect of both diseases
      on the professional qualification and occupational status which were reached in
      the end was small. The percentage of partly occupied patients and those without
      work compared to that of healthy ones. 11% of patients with Crohn's disease and
      14% with ulcerative colitis had to retire prematurely. The patients' family
      status and the number of their children matched largely that of healthy men and
      women of same age.

PMID- 8145674
TI  - [Gastroenterology update].

PMID- 8145675
TI  - [HIV-p24 antigen test in blood donors: yes or no?].

PMID- 8145676
TI  - [The boundaries between ambulatory and inpatient medicine from the viewpoint of
      cardiology, nephrology and pneumology].

PMID- 8145677
TI  - [Boundaries between ambulatory and inpatient medicine from the viewpoint of an
      established oncologist in internal medicine].

PMID- 8145678
TI  - [Ambulatory and/or inpatient oncologic treatment?].

PMID- 8145679
TI  - [Value of the HIV-p24 antigen test in blood banks].

PMID- 8145680
TI  - [Portal hypertension and pulmonary hypertension: coincidence or pathogenetic
      association? Report of two personal cases and review of the literature].

PMID- 8145681
TI  - [Current status of abdominal pancreatic ultrasound. A retrospective analysis of
      585 pancreatic ultrasound examinations].
AB  - BACKGROUND: In the recent years several investigations focused on the diagnostic
      value of abdominal ultrasonography in pancreatic disorders. However, the
      diagnostic accuracy in these studies ranged between 40 and 90% probably related
      to variations in study design and other methodologic criteria. PATIENTS: We
      examined retrospectively 585 patients subdivided into six subgroups. 385 patients
      had a clinical question aimed at the pancreas and the remaining 200 functioned as
      screening patients. RESULTS: Using laboratory tests, CT, ERCP, surgery and
      autopsy as reference methods the positive predictive value for all pancreatic
      disorders was 85% with the best results for chronic pancreatitis (86% versus
      77.5% for acute pancreatitis and 79.5% for malignant tumors). The prevalence of
      pancreatic disease in symptomatic patients was 28.6% versus only 2.5% in the
      screening groups. Therefore no significant differences could be detected in
      groups where the pancreas was not clearly visualized and groups with negative
      sonographic findings (4% false negative findings versus 1%, respectively). In
      groups with suspected pancreatic disease the negative predictive value was 86%
      which was independent of the visualization of the pancreas. CONCLUSION: In
      summary positive sonographic findings have a high predictive value for pancreatic
      disorders and negative results are not more reliable than missing visualization
      of the pancreas. The positive predictive value is independent from the kind of
      pancreatic disease and in screening examinations negative findings and findings
      without clearly visualization of the pancreas have both high negative predictive
      values.

PMID- 8145682
TI  - [Early diagnosis of HIV infections in infants at risk. A partially solved
      problem].

PMID- 8145683
TI  - [Bioelectric impedance (BIA) and thickness of the subcutaneous fatty tissue in a
      sample of normal weight and obese children].
AB  - The paper reports the results of a study on changes in the subcutaneous fat layer
      and the relations between the latter and BIA in a sample population of 105 normal
      weight and obese children of both sexes (57 males and 48 females), aged between 5
      and 14. The correlation coefficients calculated show that BI is inversely
      correlated to all the subcutaneous fat layers examined; the closes correlations
      were found in cutaneous folds on the thigh and calf in males and on the forearm
      and calf in females. The correct use of impedance measurement in children must
      take into account the difference between the sexes and those linked to the degree
      of excess weight, as well as changes in the thickness of the subcutaneous fat
      layer related to age.

PMID- 8145684
TI  - [Oxidative metabolism in polymorphonuclear granulocytes of children with trisomy
      21].
AB  - In response to certain stimuli, polymorphonuclear leukocytes (PMNs) undergo an
      oxidative burst during which a series of reactive oxygen metabolites are
      generated. The importance of the release of these oxygen metabolites by
      polymorphonuclear leukocytes, is recognized to be a key event in the function of
      these cells during infection and inflammation. We have evaluated the release of
      reactive oxygen species during the activation of respiratory burst (RB) of PMNs
      obtained from children with trisomy 21 using chemiluminescence techniques. As
      chemiluminogenic probes we have employed lucigenin and luminon that are know to
      be sensitive to the superoxide anion and the H2O2-myeloperoxidase-halide system
      of PMNs, respectively. Activated PMNs from children with trisomy 21 exhibited a
      low level of superoxide and a reduced activity of H2O2-myeloperoxidase-halide
      system compared to the control group. No significant difference in extracellular
      H2O2 release was observed. It seems likely that alterations in the enzymatic
      activities of the Cu/Zn-Superoxide dismutase and myeloperoxidase induce imbalance
      in the release of reactive oxygen species in activated PMNs from children with
      trisomy 21. This imbalance could be on the basis of the increased oxidative
      injury reported in trisomy 21.

PMID- 8145685
TI  - [Approach to acute gastroenteritis in children: comparison over the years].
AB  - Diagnostic and therapeutic approach to children admitted because of acute
      gastroenteritis has been retrospectively evaluated by auditing the hospital
      records in two periods respectively before (A: 103 patients) and after (B: 133
      patients) the use of oral rehydration solution. Incomplete history taking was
      found out without differences between the two periods; in many cases the weight
      loss, one of the main criteria for hospitalization in acute diarrhoea, was not
      recorded at admission. In period B therapeutic behaviour was adequate to
      literature guidelines as regards both antibiotic prescription and use of oral
      rehydration solution. Nevertheless even if oral rehydration was carried out in
      more than 70% of patients, parenteral fluid administration was not significantly
      reduced in comparison with period A. Oral rehydration solution contributed to
      reduce the length of hospital stay in the more recent period. The study confirms
      the usefulness of medical audit to improve quality care.

PMID- 8145686
TI  - [The use of thymopentin in the prevention of recurrent infections of the
      respiratory system. Multicenter study].
AB  - Eighty children, between 1-12 years, suffering from recurrent respiratory
      infections were admitted to a multicentre study and treated with thymopentin, an
      immunomodulating compound that represents the active site of the natural thymic
      hormone thymopoietin. Thymopentin efficacy, measured as reduction in the number
      of infective episodes, and tolerability were assessed and, at the end of the
      study a global evaluation was made by each investigator. Moreover, the following
      factors were recorded: clinical course, duration of symptoms/signs, frequency of
      administration of antipyretic, antibiotic, anti-inflammatory and mucolytic
      therapy, school attendance and hospitalization. Thymopentin treatment resulted in
      a statistically significant decrease of infective recurrences. The use of
      symptomatic and antibiotic drugs was also reduced. Side effects were few and
      mild. The investigators' overall evaluation of thymopentin's efficacy and
      tolerability was favourable. In conclusion, thymopentin, administered
      subcutaneous for 5 weeks in winter, may be useful in the treatment of children
      with recurrent infections of the respiratory tract.

PMID- 8145688
TI  - [Feto-maternal transfusion. Description of a case].
AB  - Feto-maternal transfusion is an uncommon cause of neonatal anemia due to the
      passage of fetal blood in maternal circulation, in an amount greater than 150-180
      ml. The onset of anemia may be acute or chronic in relation to the speed of blood
      loss. The case that we report has intermediate features between the acute and
      chronic form.

PMID- 8145687
TI  - [Celiac disease associated with chronic autoimmune hepatitis. Description of a
      case].
AB  - The authors describe a case of coeliac disease and autoimmune chronic hepatitis
      in the same patient. Case description allows a critical review of the literature
      and evaluation of pathogenetic hypotheses.

PMID- 8145689
TI  - [Partial trisomy of the long arm of chromosome 6. A clinical case].
AB  - The authors present the case of a child with partial trisomy of the long arm of
      chromosome 6 who was observed aged between 1 and 5 months and 5 years and 5
      months. The kariotype shows a duplication of the distal tract (6q22.36-->qter)
      deriving from the imbalance of a maternal malsegregation. The phenotype is that
      characteristic of the syndrome: microbrachycephalia with a high and prominent
      forehead, "full" orbits, exophthalmos, antimongoloid palperbral fissures,
      hypertelorism, flattened root of the nose, antiverted nostrils, small mouth with
      thin lips, micrognathy, auricles with a low implantation, short and thick neck
      with anterior palmature, low implantation of hair at nape, reduced diameter of
      chest, articular retraction, clinodactilia of 5th finger, bilateral single palmar
      groove, hypospadia. Weight, height and cranial circumference were below the 3rd
      percentile. The cases of dup (6q) reported in the literature generally describe
      similar somatic characteristics so much so that these may represent a syndrome.
      However, there is considerable variation in the level of visceral and cerebral
      impairment, only partly attributable to the degree of chromosome imbalance. The
      general conditions of the probabd were good and there was no malformation of
      internal organs. Magnetic resonance scan of the brain showed a slight increase in
      the volume of the ventricular system and a slight dilatation of the subarachnoid
      spaces with a dysmorphic cortical pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145690
TI  - [Ascaridiasis: a rare cause of recurrent abdominal pain. Report of a clinical
      case documented by ultrastructural study of the intestinal mucosa].
AB  - The case of a six-year-old girl suffering from recurrent abdominal pain is
      reported. On the basis of the laboratory tests and a number of other clinical
      investigations, the diagnosis of ascaridiasis was made. At scanning electron
      microscopy the ultrastructural study of the bioptic fragments obtained during
      endoscopy showed peculiar lesions of the gastric and duodenal mucosa. We
      speculate that this unusual picture may be due to the ascaris. These lesions,
      described for the first time in the literature to our knowledge, were represented
      by the loss of the apical portion of some cells. Differential diagnosis of
      recurrent abdominal pain is discussed.

PMID- 8145691
TI  - [Administration of 5% +EMLA cream for local anesthesia in ambulatory pediatric
      surgery].
AB  - The use of local anaesthesia has been advocated by most pediatric surgeons in
      order to cut down hospitalization costs as well as to avoid general anaesthesia.
      In 1992, 26 patients aged 4 to 14 years (avg. 8 years) underwent small surgical
      procedures with local anesthesia, obtained by the application of EMLA cream 60 to
      120 minutes prior to the procedure. EMLA cream is aneutectic mixture of lidocaine
      and prilocaine with a meeting point at a lesser temperature than the two
      compounds separately. In this way, concentration of anaesthetics increases up to
      80% in the emulsion droplets. This preparation enables small operations to be
      performed under local anesthesia even in small children who can be safely treated
      as outpatients. Disadvantages due to the long time necessary for optimal action
      can be overcome by application of the cream at home by the parents themselves.

PMID- 8145692
TI  - [Treatment of parapneumonic empyema in children].
AB  - A 31 case series of pleuropneumonia is presented, in a 7 year period. All
      patients were treated following same standards consisting of a pleural catheter
      insertion. Results support conservative treatment: short hospitalization and
      absence of psychological or physical traumas was achieved. Follow up is very good
      for all patients and none had invalidating consequences.

PMID- 8145693
TI  - Lead poisoning: it's still here.

PMID- 8145694
TI  - Limited license to retired doctors.

PMID- 8145695
TI  - The changing health care situation.

PMID- 8145696
TI  - Practice strategies for coping with "reform".

PMID- 8145697
TI  - Dermatology quiz #9. Frostbite.

PMID- 8145698
TI  - Protecting pension plans ... what's a doctor to do.

PMID- 8145699
TI  - Racial differences in the prevalence of cardiovascular risk factors among persons
      with diabetes.
AB  - Persons with diabetes are at greater risk of numerous health complications
      including coronary heart disease and stroke. We used telephone survey data to
      assess racial variations in the level of cardiovascular risk factors among
      Missouri diabetics. The four risk factors included physical inactivity, obesity,
      hypertension, and cigarette smoking. Each risk factor except smoking was more
      common among persons with diabetes than among non-diabetics. In addition, these
      risk factors were more common among Blacks than among Whites. Our results suggest
      the need for expanded efforts at controlling diabetic complications among person
      at high-risk.

PMID- 8145700
TI  - Grateful Med and Loansome Doc: easy access to the world's biomedical literature.

PMID- 8145702
TI  - New sex education policy--more of the same.

PMID- 8145701
TI  - Survival following breast-conserving surgery and irradiation or modified radical
      mastectomy in patients with invasive breast cancers with a maximum diameter of 1
      cm.
AB  - The reported relapse-free survival for women with invasive breast cancers
      measuring no more than 10 mm in dimension ranges from 75% to 95%, with axillary
      status an important prognostic factor in most series. Further study of prognostic
      variables in this most favorable subset is notably limited. We retrospectively
      reviewed the records of 168 women with invasive breast cancers < or = 10 mm
      treated with either breast conserving surgery+axillary dissection (AXD) and
      radiation therapy, or mastectomy+AXD. The actuarial survival and survival free of
      distant metastases (DMFS) at 7 years was 95% and 97%, respectively. Location and
      size of the primary tumor were most important in predicting outcome, although
      statistical significance was not achieved. The 5-year distant metastases-free
      survival (DMFS) was 100% for central and inner quadrant tumors, compared to 97%
      in those with outer quadrant tumors, p = 0.18. The 5-year DMFS was 100%, 95%, and
      98% for patients with cancers 2-5 mm, 6-9 mm, and 10 mm, respectively, p = 0.15.
      Status of the axillary lymph nodes, type of breast surgery, clinical tumor status
      (palpable vs. nonpalpable), age, menopausal status, histologic grade, systemic
      therapy, or histologic type were not found to have a significant impact on
      prognosis.

PMID- 8145703
TI  - Use of Race and Ethnicity in Public Health Surveillance. Summary of the DC/ATSDR
      workshop. Atlanta, Georgia, March 1-2, 1993.
AB  - Improvement of the health of racial and ethnic minority populations is a priority
      for CDC and the Agency for Toxic Substances and Disease Registry (ATSDR).
      Information on race and ethnicity is a critical element in public health
      surveillance efforts. To address this issue, CDC and the ATSDR conducted a 2-day
      workshop, "The Use of Race and Ethnicity in Public Health Surveillance," held in
      Atlanta on March 1-2, 1993. Workshop participants included CDC and ATSDR
      professional staff and invited experts from academia and the private sector.
      Objectives of the workshop were to: Describe the current measures of race and
      ethnicity and their use in public health surveillance at CDC/ATSDR. Assess the
      epidemiologic basis of the use of race and ethnicity in surveillance for
      planning, operation, and evaluation of public health programs at CDC/ATSDR.
      Propose better use of existing measures for race and ethnicity or to identify
      alternative measures.

PMID- 8145704
TI  - Recommendations for the prevention and management of Chlamydia trachomatis
      infections, 1993. Centers for Disease Control and Prevention.
AB  - In 1985, CDC published Policy Guidelines for Prevention and Control of Chlamydia
      trachomatis infections. Those guidelines highlighted the prevalence and morbidity
      of chlamydial infections and stressed the need to include antibiotics effective
      against chlamydia when treating patients for urethritis, mucopurulent cervicitis,
      and pelvic inflammatory disease. The recommendations presented in this report
      update the 1985 guidelines. In addition, these recommendations propose a national
      strategy for reducing the morbidity of chlamydial infections by detection and
      treatment and through the prevention of transmission to uninfected persons. Such
      an effort is now possible because of a) expanding educational efforts stimulated
      by the epidemic of acquired immunodeficiency syndrome and other sexually
      transmitted diseases, and b) the availability of chlamydia tests that are easy to
      use, economical, and accurate, thereby allowing health-care providers to diagnose
      and treat infected persons and their sex partners. Education, screening, and sex
      partner referral require coordination of the activities of several professionals,
      including educators, clinicians, microbiologists, outreach workers, and program
      managers. Because chlamydial infections are common among adolescents and young
      adults throughout the United States, health-care providers and other agencies
      serving these groups should become more involved if a sufficiently large
      proportion of the chlamydia-infected population is to be reached. Health
      departments should establish consortia of these organizations to pool resources
      and to coordinate activities. To facilitate such collaborations, this document
      outlines the elements of a chlamydia prevention program. These recommendations
      were developed by CDC after consultation with experts attending a chlamydia
      prevention workshop held in Atlanta, Georgia, March 26-28, 1991. Commentary from
      additional public health, medical, and laboratory practitioners also was
      considered in developing these recommendations.

PMID- 8145705
TI  - Recommendations for use of Haemophilus b conjugate vaccines and a combined
      diphtheria, tetanus, pertussis, and Haemophilus b vaccine. Recommendations of the
      advisory Committee on Immunization Practices (ACIP).
AB  - These recommendations include information on two vaccines recently licensed for
      use among infants: Haemophilus b Conjugate Vaccine (PRP-T [ActHIB, OmniHIB]),
      manufactured by Pasteur Merieux Vaccins, and TETRAMUNE, manufactured by Lederle
      Laboratories/Praxis Biologics. This statement also updates recommendations for
      use of other available Haemophilus b vaccines (PRP-D [ProHIBiT]; HbOC [HibTITER];
      and PRP-OMP [PedvaxHIB]) for infants and children.

PMID- 8145706
TI  - 1993 sexually transmitted diseases treatment guidelines. Centers for Disease
      Control and Prevention.
AB  - These guidelines for the treatment of patients with sexually transmitted diseases
      (STDs) were developed by staff members of CDC after consultation with a group of
      invited experts who met in Atlanta on January 19-21, 1993. Included are new
      recommendations for single-dose oral therapy for gonococcal infections,
      chlamydial infections, and chancroid; new regimens for the treatment of bacterial
      vaginosis (BV) and outpatient management of pelvic inflammatory disease (PID); a
      new patient-applied medication for treatment of genital warts; and a revised
      approach to the management of victims of sexual assault. This report includes new
      sections on subclinical human papillomavirus (HPV) infections and cervical cancer
      screening for women who attend STD clinics or who have a history of STDs. These
      recommendations also include expanded sections on the management of patients with
      asymptomatic human immunodeficiency virus (HIV) infection; vulvovaginal
      candidiasis (VVC); STDs among patients coinfected with HIV; and STDs among
      infants, children, and pregnant women.

PMID- 8145707
TI  - Tuberculosis control laws--United States, 1993. Recommendations of the Advisory
      Council for the Elimination of Tuberculosis (ACET)
AB  - Because of its communicable nature and because there are many state laws specific
      to the control of tuberculosis (TB), TB is managed differently than other
      airborne infectious diseases [corrected]. Many of these laws predate the current
      public health recommendations for the prevention and control of TB. In 1989, CDC
      published A Strategic Plan for the Elimination of Tuberculosis in the United
      States that was developed by the Advisory Committee (now Council) for the
      Elimination of Tuberculosis (ACET). The Plan called for the establishment of a
      national goal of TB elimination (i.e., achieving a case rate of < 1 per million
      population) by the year 2010. One of the methods for improving disease
      containment in the Plan was for the use of quarantine measures for nonadherent
      patients. The Plan called for revision of state and local laws to "facilitate the
      cure of persons with infectious tuberculosis". The issue of outdated state TB
      laws was also identified as a problem in the National Action Plan to Combat
      Multidrug-resistant Tuberculosis. In response to this issue, CDC conducted a
      survey of state TB control laws and ACET developed recommendations to address
      discrepancies between previously published recommendations and guidelines for the
      control of TB and state TB control laws. In order to address these discrepancies,
      states updating TB control laws should incorporate current recommendations and
      guidelines from CDC, ACET, and the American Thoracic Society. State laws should
      permit policies and practices to be rapidly reviewed and amended as new data
      becomes available and new recommendations and guidelines are published.

PMID- 8145708
TI  - Recommendations of the International Task Force for Disease Eradication.
AB  - This report summarizes the conclusions of the International Task Force for
      Disease Eradication (ITFDE), a group of scientists who were convened by a
      secretariat at the Carter Center of Emory University six times during 1989-1992.
      The purpose of the ITFDE was to establish criteria and apply them systematically
      to evaluate the potential eradicability of other diseases in the aftermath of the
      Smallpox Eradication Program. The ITFDE defined eradication as "reduction of the
      worldwide incidence of a disease to zero as a result of deliberate efforts,
      obviating the necessity for further control measures." The names of the members
      of the ITFDE, the criteria they developed and used, and summaries of the papers
      that were presented to the ITFDE by various experts are included in this report,
      as well as a brief history of the concept of disease eradication since the late
      19th century. The ITFDE considered more than 90 diseases and reviewed 30 of these
      in depth, including one noninfectious disease. It concluded that six diseases-
      dracunculiasis, poliomyelitis, mumps, rubella, lymphatic filariasis, and
      cysticercosis--could probably be eradicated by using current technology. It also
      concluded that manifestations of seven other diseases could be "eliminated," and
      it noted critical research needs that, if realized, might permit other diseases
      to be eradicated eventually. The successful eradication of smallpox in 1977 and
      the ongoing campaigns to eradicate dracunculiasis by 1995 and poliomyelitis by
      2000 should ensure that eradication of selected diseases will continue to be used
      as a powerful tool of international public health.

PMID- 8145709
TI  - Prevention and control of influenza: Part I, Vaccines. Recommendations of the
      Advisory Committee on Immunization Practices (ACIP).
AB  - These recommendations update information on the vaccine available for controlling
      influenza during the 1993-94 influenza season (superseding MMWR 1992;41(No. RR
      9):1-17.) The principal changes include information about a) the influenza
      strains in the trivalent vaccine for 1993-94, b) the effectiveness of influenza
      vaccine, and c) side effects and adverse reactions. Antiviral agents also have an
      important role in the control of influenza. Recommendations for the use of
      antiviral agents will be published later in 1993 as Part II of these
      recommendations.

PMID- 8145710
TI  - General recommendations on immunization. Recommendations of the Advisory
      Committee on Immunization Practices (ACIP).
AB  - This revision of the General Recommendations on Immunization updates the 1989
      statement. Changes in the immunization schedule for infants and children include
      recommendations that the third dose of oral polio vaccine be administered
      routinely at 6 months of age rather than at age 15 months and that measles-mumps
      rubella vaccine be administered routinely to all children at 12-15 months of age.
      Other updated or new sections include a) a listing of vaccines and other
      immunobiologics available in the United States by type and recommended routes,
      advice on the proper storage and handling of immunobiologics, a section on the
      recommended routes for administration of vaccines, and discussion of the use of
      jet injectors; b) revisions in the guidelines for spacing administration of
      immune globulin preparations and live virus vaccines, a discussion of vaccine
      interactions and recommendations for the simultaneous administration of multiple
      vaccines, a section on the interchangeability of vaccines from different
      manufacturers, and a discussion of hypersensitivity to vaccine components; c) a
      discussion of vaccination during pregnancy, a section on breast-feeding and
      vaccination, recommendations for the vaccination of premature infants, and
      updated schedules for immunizing infants and children (including recommendations
      for the use of Haemophilus influenzae type b conjugate vaccines); d) sections on
      the immunization of hemophiliacs and immunocompromised persons; e) discussion of
      the Standards for Pediatric Immunization Practices (including a new table of
      contraindications and precautions to vaccination), information on the National
      Vaccine Injury Compensation Program, the Vaccine Adverse Events Reporting System,
      and Vaccine Information Pamphlets; and f) guidelines for vaccinating persons
      without documentation of immunization, a section on vaccinations received outside
      the United States, and a section on reporting of vaccine-preventable diseases.
      These recommendations are based on information available before publishing and
      are not comprehensive for each vaccine. The most recent Advisory Committee on
      Immunization Practices (ACIP) recommendations for each specific vaccine should be
      consulted for more details.

PMID- 8145711
TI  - Guidelines for school health programs to prevent tobacco use and addiction.
      Centers for Disease Control and Prevention.
AB  - Tobacco use is the leading cause of preventable death in the United States. The
      majority of daily smokers (82%) began smoking before 18 years of age, and more
      than 3,000 young persons begin smoking each day. School programs designed to
      prevent tobacco use could become one of the most effective strategies available
      to reduce tobacco use in the United States. The following guidelines summarize
      school-based strategies most likely to be effective in preventing tobacco use
      among youth. They were developed by CDC in collaboration with experts from 29
      national, federal, and voluntary agencies and with other leading authorities in
      the field of tobacco-use prevention to help school personnel implement effective
      tobacco-use prevention programs. These guidelines are based on an in-depth review
      of research, theory, and current practice in the area of school-based tobacco-use
      prevention. The guidelines recommend that all schools a) develop and enforce a
      school policy on tobacco use, b) provide instruction about the short- and long
      term negative physiologic and social consequences of tobacco use, social
      influences on tobacco use, peer norms regarding tobacco use, and refusal skills,
      c) provide tobacco-use prevention education in kindergarten through 12th grade,
      d) provide program-specific training for teachers, e) involve parents or families
      in support of school-based programs to prevent tobacco use, f) support cessation
      efforts among students and all school staff who use tobacco, and g) assess the
      tobacco-use prevention program at regular intervals.

PMID- 8145712
TI  - Water hemlock poisoning--Maine, 1992.

PMID- 8145713
TI  - Health-risk behaviors among persons aged 12-21 years--United States, 1992.
AB  - Health-risk behaviors among youth may result in immediate health problems (e.g.,
      injuries and sexually transmitted diseases) or extend into adulthood and increase
      risk for chronic diseases (e.g., heart disease and cancer). This report uses
      national data from the Youth Risk Behavior Survey (YRBS), conducted as part of
      the 1992 National Health Interview Survey (NHIS), to examine the prevalence of
      selected self-reported health-risk behaviors among persons aged 12-21 years.

PMID- 8145714
TI  - Fatalities associated with harvesting of sea urchins--Maine, 1993.
AB  - During 1992-1993, six persons died while diving for sea urchins in Maine waters-
      two during 1992 and four during August-November 1993. The four 1993 deaths were
      investigated by the Maine Department of Marine Resources, the U.S. Coast Guard,
      the Office of the Chief Medical Examiner in Maine, and the Occupational Safety
      and Health Administration (OSHA); each of the deaths was attributed to drowning.
      This report describes the results of the investigations of these cases.

PMID- 8145715
TI  - Human plague--United States, 1993-1994.
AB  - From 1944 through 1993, 362 cases of human plague were reported in the United
      States; approximately 90% of these occurred in four western states with endemic
      disease (Arizona, California, Colorado, and New Mexico). During each successive
      decade of this period, the number of states reporting cases increased from three
      during 1944-1953 to 13 during 1984-1993 (Figure 1), indicating the spread of
      human plague infection eastward to areas where cases previously had not been
      reported. In 1993, health departments in four states reported 10 confirmed cases
      of human plague to CDC; one case has been confirmed during 1994. This report
      summarizes information about the 11 cases of human plague reported during 1993
      1994 and describes epidemiologic and epizootic trends of plague in the United
      States.

PMID- 8145716
TI  - Adult blood lead epidemiology and surveillance--United States, fourth quarter,
      1993.

PMID- 8145717
TI  - Motor-vehicle-related deaths involving intoxicated pedestrians--United States,
      1982-1992.
AB  - Pedestrians account for 14% of all motor-vehicle-related deaths and approximately
      3% of all motor-vehicle-related injuries in the United States. In 1992, a total
      of 5546 pedestrians were killed as a result of motor-vehicle crashes, and 96,000
      suffered nonfatal injuries. Because of the effects of alcohol on attention,
      perception, vision, judgment, and motor control, intoxicated pedestrians are at
      increased risk for unintentional injury. Although alcohol consumption by
      pedestrians is an important contributing factor to motor-vehicle crashes in which
      pedestrians are injured, characteristics of intoxicated pedestrians who are
      killed as a result of such crashes have not been well defined. This report uses
      data from the National Highway Traffic Safety Administration's (NHTSA) Fatal
      Accident Reporting System for 1982-1992 to characterize intoxicated pedestrians
      aged > 14 years who were killed as a result of motor-vehicle-related crashes.

PMID- 8145718
TI  - Homicides of persons aged < or = 18 years--Fulton County, Georgia, 1988-1992.
AB  - Homicide is a major cause of death among persons aged < or = 18 years in the
      United States; among black males aged 15-24 years, homicide is the leading cause
      of death. Most efforts to characterize homicide among persons aged < or = 18
      years have used databases at the national level rather than at the state or local
      level or have been restricted in scope to specific types of homicides (e.g., gang
      related homicide. This report summarizes an epidemiologic study of homicides that
      occurred among persons aged < or = 18 years in Fulton County (Atlanta), Georgia
      (1990 population: 648,951), from 1988 through 1992.

PMID- 8145719
TI  - Occupational injury deaths--United States, 1980-1989.
AB  - During 1980-1989, 63,589 workers died from occupational injuries, an average of
      17 deaths per day. CDC's National Institute for Occupational Safety and Health
      (NIOSH) monitors occupational injury deaths through the National Traumatic
      Occupational Fatalities (NTOF) surveillance system. This report summarizes
      occupational injury deaths compiled by NTOF* for 1980-1989.

PMID- 8145720
TI  - National infant immunization week.

PMID- 8145721
TI  - Publication of Special NIOSH hazard review of the rubber products manufacturing
      industry.

PMID- 8145722
TI  - Publication of NEG and NIOSH basis for an occupational health standard: ethyl
      ether.

PMID- 8145723
TI  - Cloning and expression of a new member of the L-2-amino-4-phosphonobutyric acid
      sensitive class of metabotropic glutamate receptors.
AB  - Despite the cloning of several metabotropic glutamate receptors (mGluR1-6), the
      activity and localization of the cloned mGluRs do not account for the action of L
      2-amino-4-phosphonobutyric acid (L-AP4) on mitral/tufted cells in the rat
      olfactory bulb. Thus, we screened a rat olfactory bulb library for novel cDNA
      clones, using probes derived from mGluR1 and mGluR4. A full length cDNA clone
      encoding a metabotropic receptor (mGluR7) whose sequence was 69% identical to
      that of mGluR4 was isolated. Stimulation of mGluR7 with L-AP4 and glutamate (each
      at 1 mM) in stably transfected baby hamster kidney cells inhibited forskolin
      stimulated cAMP formation, whereas ACPD (1 mM) and quisqualate (0.5 mM) were less
      effective. Inhibition of cAMP required high concentrations of agonist in the
      transfected cells, suggesting that inhibition of adenylate cyclase may not be the
      predominant transduction mechanism for this receptor in neurons. RNA blot
      analysis and in situ hybridization revealed that mGluR7 has an expression pattern
      in the central nervous system distinct from that of other L-AP4-sensitive mGluRs.
      Double-labeling with probes for mGluR1 and mGluR7 revealed that individual
      mitral/tufted neurons in the olfactory bulb expressed both mRNAs. The expression
      pattern and L-AP4 sensitivity of mGluR7 suggest that it mediates inhibition of
      transmitter release at selected glutamatergic synapses. The coexpression of
      multiple mGluR mRNAs in single neurons indicates that the cellular effects of
      mGluR activation are likely to result from the integrated action of several
      receptor subtypes.

PMID- 8145724
TI  - Secondary structure of amyloid beta peptide correlates with neurotoxic activity
      in vitro.
AB  - Amyloid beta peptide (A beta), the major protein constituent of senile plaques in
      patients with Alzheimer's disease, is believed to facilitate the progressive
      neurodegeneration that occurs in the latter stages of this disease. Early
      attempts to characterize the structure-activity relationship of A beta toxicity
      in vitro were compromised by the inability to reproducibly elicit A beta
      dependent toxicity across different lots of chemically equivalent peptides. In
      this study we used CD spectroscopy to demonstrate that A beta secondary structure
      is an important determinant of A beta toxicity. Solubilized A beta was maximally
      toxic when the peptide adopted a beta-sheet conformation. Three of the four A
      beta lots tested had a random coil conformation and were weakly toxic or
      inactive, whereas the single A beta lot exhibiting toxic activity at low peptide
      concentrations had significant beta-sheet structure. Incubation of the weakly
      toxic A beta lots in aqueous stock solutions for several days before use induced
      a time-dependent conformational transition from random coil to beta-sheet and
      increased A beta toxicity in three different toxicity assays. Furthermore, the
      secondary structure of preincubated A beta was dependent upon peptide
      concentration and pH, so that beta-sheet structures were attenuated when peptide
      solutions were diluted or buffered at neutral and basic pH. Our data could
      explain some of the variable toxic activity that has been associated with A beta
      in the past and provide additional support for the hypothesis that A beta can
      have a causal role in the molecular neuropathology of Alzheimer's disease.

PMID- 8145725
TI  - Sensitization of adenylate cyclase by halothane in human myocardium and S49
      lymphoma wild-type and cyc- cells: evidence for inactivation of the inhibitory G
      protein Gi alpha.
AB  - Halothane has been reported to sensitize the myocardium towards the effects of
      exogenous catecholamines in patients and laboratory animals. This study was aimed
      at investigating the catecholamine-sensitizing effects of halothane as well as
      the underlying subcellular mechanisms in human myocardium. Halothane augmented
      the positive inotropic effect of isoprenaline but not of Ca2+. The increase of
      the effect of isoprenaline by halothane was more pronounced in failing
      myocardium, with increased Gi, than in nonfailing donor hearts. Halothane (1%)
      increased basal as well as isoprenaline-, NaF-, cholera toxin-, and
      guanylylimidodiphosphate [Gpp(NH)p]-stimulated adenylate cyclase in human
      myocardial membranes (p < 0.05). Treatment of membranes with pertussis toxin
      increased adenylate cyclase by 40% and abolished the effect of halothane.
      Halothane had no effect on forskolin-stimulated adenylate cyclase. The same
      results, i.e., a pertussis toxin-sensitive increase of adenylate cyclase
      stimulation by halothane, were obtained in S49 cyc-, wild-type, or recombinant Gs
      alpha-reconstituted cyc- cell membranes. Carbachol-stimulated guanosine-5'-O-(3
      [35S]thio)triphosphate binding was not influenced by halothane, but halothane
      attenuated the inhibition of adenylate cyclase by Gpp(NH)p in S49 cyc- cells.
      These data show that halothane stimulates adenylate cyclase and sensitizes
      adenylate cyclase after stimulation by beta-adrenoceptor agonists and guanine
      nucleotides due to an impairment of Gi alpha function. This mechanism may play a
      role in the halothane sensitization of myocardial adenylate cyclase towards
      catecholamines.

PMID- 8145726
TI  - Systemic dexamethasone administration increases septal Trk autophosphorylation in
      adult rats via an induction of nerve growth factor.
AB  - Nerve growth factor (NGF) maintains cholinergic neurons in various animals models
      of neurodegeneration and is thus a potential treatment for certain
      neurodegenerative disorders such as Alzheimer's disease. Because NGF does not
      cross the blood-brain barrier, we have proposed elevating endogenous levels of
      NGF in the central nervous system with small molecules that induce NGF
      expression, as an alternative strategy. The present studies were conducted to
      determine whether pharmacologically elevated levels of NGF are sufficient to
      cause subsequent stimulation of its high affinity receptor, as measured by
      increased levels of Trk phosphorylation. Dexamethasone (0.5-20 mg/kg,
      intraperitoneally) caused a time- and dose-dependent increase in NGF mRNA and NGF
      protein in the hippocampus and septum of adult male Sprague-Dawley rats.
      Exogenously administered NGF (1 microgram, intracerebroventricularly) led to a
      rapid (30 min) and transient increase in Trk phosphorylation in the septum, which
      has high levels of NGF-specific TrkA. Similarly, dexamethasone led to an increase
      in Trk phosphorylation only within the septum. Dexamethasone-mediated Trk
      phosphorylation was dose and time dependent, with peak increases being observed
      12 hr after injection, concurrently with peak increases in NGF protein. These
      data demonstrate an increase in activation of the high affinity NGF receptor with
      a compound that elevates levels of NGF in the central nervous system, and they
      support the strategy of discovering a pharmacological agent that induces NGF as a
      method for treating neurodegenerative disorders.

PMID- 8145727
TI  - Pituitary cell line GH3 expresses two somatostatin receptor subtypes that inhibit
      adenylyl cyclase: functional expression of rat somatostatin receptor subtypes 1
      and 2 in human embryonic kidney 293 cells.
AB  - Using a polymerase chain reaction approach, we have studied the expression of
      somatostatin receptor (SSTR) subtypes in the GH3 rat pituitary cell line, a well
      established in vitro model for the cellular effects of somatostatin. We found
      that the previously identified SSTR1 and SSTR2 are the major subtypes expressed
      in this cell line. No other SSTR subtype was detected by our analysis. Northern
      blots confirmed that both subtypes, but not SSTR3, are expressed in GH3 cells. We
      studied the functional expression of both SSTR subtypes by transfection of their
      cDNAs into human embryonic kidney 293 cells. We found that somatostatin inhibited
      cAMP accumulation in human embryonic kidney 293 cells only when cells were
      transfected with either SSTR1 or SSTR2. This inhibition was blocked by treatment
      of the transfected cells with pertussis toxin, demonstrating that it is mediated
      by G proteins sensitive to this toxin. In addition, we provide pharmacological
      evidence that the endogenous SSTR2 subtype mediates inhibition of cAMP
      accumulation in intact GH3 cells. Our results contradict previous reports that
      concluded thsat neither SSTR1 nor SSTR2 is involved in inhibition of adenylyl
      cyclase. The reasons for this apparent contradiction are discussed. We conclude
      that both SSTR1 and SSTR2 are capable of coupling to pertussis toxin-sensitive G
      proteins to inhibit adenylyl cyclase.

PMID- 8145728
TI  - Rat somatostatin receptor type 1 couples to G proteins and inhibition of cyclic
      AMP accumulation.
AB  - The pharmacology, signal transduction, and coupling to G proteins of the rat
      somatostatin (SRIF) receptor (SSTR)1 have been characterized in transfected
      Chinese hamster ovary (CHO) (K1 strain) cells. The expressed receptor exhibited
      saturable, high affinity binding of several radioiodinated SRIF analogues. Three
      different radioligands were used to determine the pharmacological properties of
      this SSTR subtype. [125I-Tyr11]SRIF-14 (125I-S-14), [Leu8,D-Trp22,125I-Tyr25]SRIF
      28 (125I-S-28), and cyclo(D-Trp-Lys-Abu-Phe-MeAla-125I-Tyr) (125I-peptide C)
      displayed the following rank order of affinity (Kd) for the SSTR1 subtype: 125I-S
      14 > or = 125I-S-28 > 125I-peptide C. Competition of 125I-S-14 with S-14, S-28,
      or peptide C displayed the same rank order of potency. Chemical cross-linking of
      specifically bound 125I-S-28 to membranes from CHO cells expressing the receptor
      indicated that the molecular weight of the SSTR1 expressed in CHO cells is
      approximately 70,000, suggesting that it is heavily glycosylated. Previous
      reports have suggested that the human SSTR1 [Mol. Pharmacol. 42:28-34 (1992)]
      couples poorly to G proteins. The coupling of the rat SSTR1 to G proteins was
      demonstrated by three independent methods. (a) Binding of 125I-S-14 to the SSTR1
      subtype was inhibited in a dose-dependent fashion by incubation of membranes with
      guanosine-5'-O-(3-thio)triphosphate. (b) Treatment of cells with pertussis toxin
      decreased binding by 80%. (c) Immunoprecipitation of 125I-S-14 binding was
      observed with antiserum specific for Gi alpha 1,2, but not with antiserum
      specific for Gs alpha, in membranes from transfected cells. In CHO cells
      transfected with the SSTR1 cDNA, SRIF inhibited forskolin-stimulated cAMP
      accumulation by up to 50%, in a dose-dependent fashion (ED50 = 1.1 nM). Pertussis
      toxin treatment decreased both the efficacy and the potency of the SRIF-mediated
      inhibition of cAMP accumulation (from 50% to 22%), compared with control
      untreated cells. These data suggest that the rat SSTR1 inhibits cAMP accumulation
      by coupling to pertussis toxin-sensitive G proteins.

PMID- 8145729
TI  - The aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator
      protein show distinct subcellular localizations in Hepa 1c1c7 cells by
      immunofluorescence microscopy.
AB  - The aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (Arnt) protein
      were evaluated in the Hepa 1c1c7 (Hepa-1) cell line by indirect
      immunofluorescence microscopy and Western blot analysis. Wild-type (WT) Hepa-1
      cells stained for AhR show intense cytoplasmic fluorescence with minimal nuclear
      reactivity. WT cells treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) show
      a time-dependent decrease in cytoplasmic AhR staining and a concomitant increase
      in nuclear fluorescence. WT cells stained for Arnt show nuclear fluorescence with
      minimal cytoplasmic reactivity, a pattern unchanged after TCDD treatment. Hepa-1
      type II variants express normal levels of AhR but are defective in TCDD-mediated
      induction of cytochrome P4501A1. Type II variants stained for Arnt show reduced
      nuclear fluorescence, compared with WT cells, and express minimal levels of Arnt
      protein, as determined by Western blot analysis. Type II variants stained for the
      AhR show intense cytoplasmic fluorescence that becomes nuclear after TCDD
      treatment. Detailed evaluation by immunoelectron microscopy of the AhR and Arnt
      present in the nuclear compartment of WT cells shows that both proteins are
      uniformly distributed and do not appear to be associated with nuclear pores,
      membranes, or nucleoli. Western blot analysis of nuclei isolated from WT Hepa-1
      cells fractionated with Nonidet P-40 shows that minimal levels of AhR or Arnt are
      retained in the nuclear fraction after TCDD treatment. Collectively, these
      results indicate that the unliganded AhR resides in the cytoplasm, Arnt is
      localized to the nucleus, and Hepa-1 cells defective in Arnt expression exhibit
      TCDD-mediated nuclear accumulation of the AhR.

PMID- 8145730
TI  - Localization of a pioglitazone response element in the adipocyte fatty acid
      binding protein gene.
AB  - The thiazolidinediones are a class of antidiabetic compounds that increase the
      sensitivity of target tissues to insulin. An earlier study has shown that these
      compounds enhance the insulin-stimulated differentiation of 3T3-L1 cells and up
      regulate expression of differentiation-dependent genes. We have observed that the
      mRNA encoding the adipocyte fatty acid-binding protein (aFABP) increases shortly
      after incubation of cells with pioglitazone, a thiazolidinedone analogue. The
      drug was found to enhance, in a time- and dose-dependent fashion, the expression
      of a chimeric gene that was constructed by fusing the aFABP promoter upstream of
      the chloramphenicol acetyltransferase (CAT) gene. To localize the sequence within
      the promoter that is responsive to pioglitazone, a series of chimeric genes
      containing sections of the aFABP promoter fused to the CAT gene were analyzed
      after transfection of 3T3-L1 cells. A section of DNA located at -5.2 kilobases
      and known to encompass a tissue-specific and differentiation-dependent enhancer
      element was found to confer responsiveness to the drug. Analysis of sequences in
      this region of the aFABP promoter by DNA gel retardation assays revealed the
      presence of a protein in nuclear extracts from drug-treated cells that bound to a
      specific sequence (ARE-6). The presence of the protein could be demonstrated in
      differentiated adipocytes, but the protein was present at only low levels in
      preadipocytes. Treatment of preadipocytes with pioglitazone resulted in the
      precocious appearance of this protein in nuclear extracts. Multiple copies of the
      ARE-6 sequence inserted upstream of a heterologous promoter linked to the CAT
      gene conferred pioglitazone responsiveness. The experiments reported in this
      study establish that the insulin-sensitizing agent pioglitazone up-regulates
      expression of the aFABP gene through an element located within a region of DNA
      responsible for tissue-specific and differentiation-dependent expression of the
      gene.

PMID- 8145731
TI  - Antimalarial action of hydrophilic drugs: involvement of aqueous access routes to
      intracellular parasites.
AB  - The antimalarial action and intracellular distribution of the hydrophilic agents
      phloridzin (PHL) (a bioflavonoid glycoside) and desferrioxamine (DFO) (an iron
      chelator) were studied in cultures of Plasmodium falciparum-infected human
      erythrocytes. When added to cultures, these agents arrested parasite growth with
      IC50 values of 12 microM (PHL) and 22 microM (DFO). At 37 degrees, PHL (40
      microM) was virtually impermeant to uninfected cells but permeated with a mean
      t1/2 of 1.5 hr in trophozoites (30% accessible cell volume) and 8 hr in rings
      (10% of accessible cell volume). PHL, in analogy with DFO, was demonstrably
      permeant to infected cells harboring mature forms of the parasites. Permeation
      was restricted to only a fraction of the infected cell volume. PHL elicited
      inhibition of nucleic acid synthesis within 1 hr of exposure of trophozoites to
      PHL (40 microM) and in > 8 hr of exposure of rings. Red cell containers into
      which millimolar concentrations of PHL or DFO were encapsulated demonstrably
      supported parasite invasion and subsequent parasite growth and maturation (48-hr
      incubation). Under culture conditions, uninfected or parasite-infected red cell
      containers that were loaded with either agent retained the drugs for at least 42
      hr at hundred-micromolar concentrations. The agent present in the cells was fully
      active after release from cells and administration to test cultures of parasites.
      PHL added to parasite cultures was active at micromolar concentrations, but when
      present intracellularly it was virtually inactive even at millimolar
      concentrations. The data presented are consistent with direct access of
      hydrophilic agents from medium to parasite, a process referred to as
      fenestration. Permeation into parasites might constitute the rate-limiting step
      in drug uptake and drug-mediated arrest of parasite growth by PHL and DFO. The
      putative role of the parasitophorous duct in providing aqueous access routes from
      medium to parasites is discussed.

PMID- 8145732
TI  - Human histamine N-methyltransferase pharmacogenetics: cloning and expression of
      kidney cDNA.
AB  - Histamine N-methyltransferase (HNMT) catalyzes the NT-methylation of histamine.
      The level of HNMT activity in human red blood cells is controlled by a common
      genetic polymorphism. We set out to clone and express a cDNA for HNMT from human
      tissue as a first step toward a determination of the molecular basis for this
      genetic polymorphism. The cloning strategy was based on possible sequence
      homology between rat and human kidney HNMT. Human kidney cDNA libraries were
      screened with the 885-nucleotide open reading frame of rat kidney HNMT cDNA. A
      1.4-kilobase cDNA clone was isolated that contained two potential translation
      initiation codons, both in the same reading frame. The longest open reading frame
      of the human kidney cDNA clone contained 876 nucleotides and encoded a protein
      292 amino acids in length. The amino acid sequence of this protein was 84%
      identical to that of rat kidney HNMT. The human kidney cDNA clone was transcribed
      in vitro and translated in a rabbit reticulocyte lystate system to yield a
      protein with an apparent molecular mass of 33 kDa, as estimated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The human kidney cDNA was also
      subcloned into the eukaryotic expression vector p91023(B). Partially purified
      HNMT isolated from the cytosol of GOS-1 cells transfected with this expression
      construct had biochemical properties similar to those of human kidney HNMT. Human
      renal cortical HNMT, partially purified human renal cortical HNMT, and partially
      purified transfected COS-1 cell HNMT had Km values for histamine and S-adenosyl-L
      methionine, the two cosubstrates for the enzyme reaction, of 20, 13, and 14
      microM and 2.0, 3.0, and 6.2 microM, respectively. IC50 values for the HNMT
      inhibitor amodiaquine were 0.50, 0.48, and 0.40 microM, respectively, for enzyme
      from these same three sources. Northern blot analyses performed with poly(A)+ RNA
      from a series of human tissues including kidney demonstrated three transcripts,
      approximately 1.3, 3.8, and 4.0 kilobases in length. Cloning of a cDNA for HNMT
      may now make it possible to determine the molecular basis for the HNMT genetic
      polymorphism in humans.

PMID- 8145733
TI  - Formation of heteromeric gamma-aminobutyric acid type A receptors containing two
      different alpha subunits.
AB  - The functional properties of recombinant gamma-aminobutyric acid (GABA) receptors
      expressed transiently in human embryonic kidney 293 cells were examined.
      Combinations of alpha 1 beta 2 gamma 2, alpha 3 beta 2 gamma 2, and alpha 1 alpha
      3 beta 2 gamma 2 subunits were transiently expressed and the properties of the
      resulting receptors were studied with patch-clamp electrophysiology. Each subunit
      combination produced receptors having a unique set of functional properties.
      Concentration-response experiments showed that receptors composed of alpha 1 beta
      2 gamma 2 subunit combinations were more sensitive to GABA (EC50 = 17.4 microM)
      than were either alpha 3 beta 2 gamma 2 (EC50 = 103 microM) or alpha 1 alpha 3
      beta 2 gamma 2 (EC50 = 55.8 microM) receptors. Consistent with its action at
      native GABA-A receptors, diazepam (1 microM) potentiated the effect of GABA by
      shifting the GABA concentration-response curve to the left. The magnitude of the
      diazepam shift also differed between subunit combinations. The apparent potency
      of GABA was increased 2-fold by diazepam with alpha 1 beta 2 gamma 2 receptors, 3
      fold with alpha 3 beta 2 gamma 2 receptors, and 5-fold with alpha 1 alpha 3 beta
      2 gamma 2 receptors. Brief applications (6-25 msec) of 3 mM GABA to outside-out
      patches revealed that currents decayed predominantly with double-exponential time
      courses. The decay time courses of currents mediated by alpha 1 beta 2 gamma 2
      and alpha 1 alpha 3 beta 2 gamma 2 receptors were similar, whereas the alpha 3
      beta 2 gamma 2 receptor response decayed more slowly. The distinct properties
      observed in cells expressing each of these subunit combinations suggest that the
      subunits form unique receptors. The possibility that some neuronal GABA receptors
      contain two different alpha subunits is discussed.

PMID- 8145734
TI  - Differential expression of the beta-adrenergic receptor modifies agonist
      stimulation of adenylyl cyclase: a quantitative evaluation.
AB  - The effect of varying levels of beta 2-adrenergic receptor (beta AR) expression
      on the capacity of the receptor to activate adenylyl cyclase through regulatory G
      proteins has been systematically explored in this paper, using differential
      expression of hamster and human beta AR in L cells. Equations have been developed
      based on the cycle of G protein activation first proposed by Cassel and Selinger
      and the mobile receptor model, which assumes that hormone-bound beta AR can
      stimulate a number of different adenylyl cyclase moieties through the G protein
      during a single cycle of activation. These equations predict the relationship of
      receptor number to the EC50 (potency) and Vmax (efficacy) for adenylyl cyclase
      activation. L cell clones were selected with stable expression of the beta AR
      over a 2000-fold range of levels (from 5 to 10,000 fmol/mg of membrane protein).
      Experimentally determined values for the EC50 and the Vmax for epinephrine
      stimulation of adenylyl cyclase over the entire range of receptor levels were
      found to be in excellent agreement with predictions of the traditionally accepted
      models. A method is introduced that allows calculation of beta AR coupling
      efficiency while taking into account the effect of variable receptor levels. The
      approach provides a quantitative means for the determination of coupling
      efficiency of the receptor/G protein/adenylyl cyclase system over wide variations
      in receptor levels and allows for a rational comparison of coupling efficiencies
      of wild-type and mutant receptors when receptor levels differ.

PMID- 8145735
TI  - Evidence for a common molecular mode of action for chemically distinct nonpeptide
      antagonists at the neurokinin-1 (substance P) receptor.
AB  - The molecular mechanism of action of three chemically distinct nonpeptide
      antagonists, SR 140,333, FK 888, and RP 67,580, was compared with that of the
      previously characterized compound CP 96,345, using a series of chimeric
      constructs between their common target, the rat neurokinin (NK)-1 (substance P)
      receptor, and the homologous nonresponsive NK-3 (NKB) receptor. The ability of
      all four nonpeptide compounds to displace radiolabeled substance P from the NK-1
      receptor and their ability to inhibit the peptide-induced increase in inositol
      phosphate turnover were critically dependent on structural elements located in an
      area from the middle of the second extracellular loop through transmembrane
      segments V and VI to the middle of the third extracellular loop of the NK-1
      receptor. Dissection of the domain around the outer part of transmembrane
      segments V and VI into smaller segments demonstrated that the individual
      nonpeptide antagonists, in agreement with their distinct chemical structures,
      were dependent on different subepitopes within the common putative binding
      domain. Full NK-1-like susceptibility to SR 140,333, FK 888, and CP 96,345 could
      be transferred to the NK-3 receptor by exchange of transmembrane segments V and
      VI and adjacent parts with corresponding segments from the NK-1 receptor. For SR
      140,333 and CP 96,345, almost the same effect could be achieved by transfer of
      two discontinuous segments around the top of transmembrane segments V and VI. RP
      67,580 shared interaction sites with the other compounds around the top of
      transmembrane segment VI but appeared also to be dependent on transmembrane
      segment VII. It is concluded that four nonpeptide antagonists, despite overt
      chemical differences, appear to block NK-1 receptor function by interacting in
      distinct ways with a common site located spatially around the outer part of
      transmembrane segment VI.

PMID- 8145736
TI  - An arginine residue conserved in most G protein-coupled receptors is essential
      for the function of the m1 muscarinic receptor.
AB  - An exceptionally conserved sequence that is shared among most G protein-coupled
      neurotransmitter receptors is an aspartate-arginine-tyrosine triplet that is
      located at the amino terminus of the putative second cytoplasmic domain, where
      the arginine residue is invariant. Using the m1 subtype of muscarinic
      acetylcholine receptors as an example, we induced a point mutation of the
      arginine residue at position 123 into asparagine. This mutation resulted in a
      precipitous decrease in the coupling of m1 receptors to activation of
      phosphoinositide hydrolysis, in spite of the expression of the wild-type and
      mutant receptors at similar concentrations in Chinese hamster ovary cells. There
      were no significant effects on antagonist or partial agonist binding. In marked
      contrast, whereas binding of the full agonist carbachol to wild-type receptors
      exhibited high and low affinity components, this agonist bound to a single low
      affinity state in asparagine-123 mutant cells. Furthermore, agonist-induced
      enhancement of the specific binding of guanosine-5'-O-(3-[35S] thio)triphosphate
      was not observed in membranes of cells expressing the mutant receptor. A similar
      mutation in the m2 muscarinic receptor resulted in a significant but smaller
      decrease in its coupling to inhibition of cAMP formation. On the other hand, a
      point mutation of tyrosine-124 in the m1 receptor sequence produced less marked
      changes in agonist-induced phosphoinositide hydrolysis and no effects on agonist
      or antagonist binding to the receptor. Taken together, our data demonstrate for
      the first time that this highly conserved arginine residue plays an important
      role in coupling of muscarinic receptors to signal transduction mechanisms.

PMID- 8145737
TI  - Determinants of alpha 2-adrenergic receptor activation of G proteins: evidence
      for a precoupled receptor/G protein state.
AB  - The ability of agonist-occupied alpha 2D-adrenergic receptors to activate G
      proteins was measured in membranes from PC-12 cells stably expressing the cloned
      receptor, using guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S)
      binding as an endpoint. Epinephrine (EPI) stimulated [35S]GTP gamma S binding in
      a Mg(2+)-dependent manner, showing both micromolar and millimolar cation
      affinities. Prior treatment of cells with pertussis toxin completely eliminated
      the EPI stimulation. The presence of GDP decreased basal [35S]GTP gamma S binding
      and increased the proportion of EPI-stimulated binding. Increasing concentrations
      of Na+ also reduced basal [35S]GTP gamma S binding but had less effect on EPI
      stimulated binding, such that the agonist response was proportionately greater at
      higher Na+ levels. In saturation binding studies with [35S]GTP gamma S only low
      affinity binding was observed in the presence of 100 mM Na+, whereas in the
      absence of Na+ a high affinity component was also present, indicating a Na(+)
      regulated receptor/G protein interaction. EPI induced high affinity [35S]GTP
      gamma S binding in the presence of Na+ and increased the affinity of the high
      affinity component under Na(+)-free conditions. The selective alpha 2-adrenergic
      antagonist rauwolscine produced rightward shifts of EPI dose-response curves and
      decreased the basal level of [35-S]GTP gamma S binding across the same range of
      concentrations. The extent of decrease was dependent upon the alpha 2-adrenergic
      receptor expression level, indicating that alpha 2-adrenergic receptors
      contribute to basal G protein activation in the absence of agonist. The ability
      of rauwolscine to decrease basal [35S]GTP gamma S binding was diminished as the
      level of Na+ was increased, suggesting that both agents act to reduce receptor/G
      protein interaction, by distinctive mechanisms. alpha 2-Adrenergic receptor
      antagonists reduced basal G protein activation with a rank order for maximal
      effectiveness that was different from their receptor binding affinities. These
      results support the existence of precoupling between alpha 2D-adrenergic
      receptors and G proteins; coupling can be diminished by both Na+ and antagonists,
      whereas agonists increase the efficiency of receptor/G protein coupling.

PMID- 8145738
TI  - Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH
      SY5Y cell line and determination of pharmacological properties of native
      receptors and functional alpha 7 homomers expressed in Xenopus oocytes.
AB  - The alpha-bungarotoxin-binding acetylcholine receptors from the human
      neuroblastoma cell line SH-SY5Y were found to cross-react with some monoclonal
      antibodies to alpha 7 subunits of nicotinic acetylcholine receptors from chicken
      brain. The human alpha 7 subunit cDNA from SH-SY5Y was cloned, revealing 94%
      amino acid sequence identity to rat alpha 7 subunits and 92% identity to chicken
      alpha 7 subunits. Native human alpha 7 receptors showed affinities for some
      ligands similar to those previously observed with native chicken alpha 7
      receptors, but for other ligands there were large species-specific differences in
      binding affinity. These results paralleled properties of alpha 7 homomers
      expressed in Xenopus oocytes. Human alpha 7 homomers exhibited rapidly
      desensitizing, inwardly rectifying, agonist-induced, cation currents that
      triggered Ca(2+)-sensitive Cl- channels in the oocytes. A change in efficacy from
      partial agonist for chicken alpha 7 homomers to full agonist for human alpha 7
      homomers was exhibited by 1,1-dimethyl-4-phenylpiperazinium. This result reveals
      a large species-specific pharmacological difference, despite small differences in
      alpha 7 sequences. This is important for understanding the effects of these drugs
      in humans and for identifying amino acids that may contribute to the
      acetylcholine binding site, for analysis by in vitro mutagenesis. These results
      also characterize properties of native alpha 7 receptors and alpha 7 homomers
      that will provide criteria for functional properties expected of structural
      subunits, when these can be identified, cloned, and coexpressed with alpha 7
      subunits.

PMID- 8145739
TI  - Role of tyrosine 337 in the binding of huperzine A to the active site of human
      acetylcholinesterase.
AB  - Huperzine A (HUP), a natural, potent, 'slow,' reversible inhibitor of
      antiacetylcholinesterase (AChE), has been suggested to be superior to
      antiacetylcholinesterase drugs now being used for management of Alzheimer's
      disease. To delineate the binding site of human AChE (HuAChE) for HUP, the
      biochemical constants kon, koff, and Ki were determined for complexes formed
      between HUP and single-site (Y337F, Y337A, F295A, W286A, and E202Q) or double
      site (F295L/F297V) mutants of recombinant HuAChE (rHuAChE). The kinetic and
      dissociation constants were compared with those obtained for wild-type rHuAChE
      and AChE from Torpedo californica. Results demonstrate that the inhibition of
      AChE by HUP occurs through association with residues located inside the active
      site 'gorge,' rather than at the rim of the gorge. Tyrosine at position 337
      (Y337) is essential for inhibition of rHuAChE by HUP (Ki = 26 nM). An aromatic
      array constituted from residues Y337, F295, and probably W86 is likely to offer a
      multicontact subsite that interacts with the ammonium group and with both the exo
      and endocyclic double bond moieties of HUP. Lack of the aromatic side chain in
      the position homologous to Y337 explains the poor inhibitory potency of HUP
      toward human butyrylcholinesterase (Ki > 20,000 nM). Replacement of the
      carboxylate-containing E202 by glutamine had only marginal effect on the
      stability of the complex formed between HUP and rHuAChE. The pH-rate profiles
      suggest that destabilization of the complex after proton gain cannot be
      attributed solely to protonation of E202. These findings are expected to
      establish HUP as a lead compound for the design of new anti-AChE drugs.

PMID- 8145740
TI  - [Activity of c-myc protein is necessary in the first 6 hours of the
      prereplicative period for 3T3 Swiss cells].
AB  - It was shown what microinjection of polyclonal antibodies to the myc protein
      specifically inhibits DNA synthesis in serum-stimulated 3T3 Swiss cells during
      the first 6 h of the prereplicative period. The effect depends on the
      concentration of antibodies. Microinjections of polyclonal antibodies against the
      whole protein were more effective when microinjections of antibodies against
      parts of the protein. Microinjections of five kinds of monoclonal antibodies and
      their mixture were in effective. It was also shown what induction of expression
      of the antisense myc sequence in 3T3 Swiss cells leads to potent inhibition of
      DNA synthesis during the first 6 h of the prereplicative period. Thus it is clear
      what the myc protein participates in the early stages of preparation to
      replication, i.e., transition of cells from G0 to G1.

PMID- 8145741
TI  - [Study of anti-HIV activity of azidothymidine and fluorothymidine 5'
      phosphonates].
AB  - It was established that 5'-phosphonates of 3'-azido-2',3'-dideoxythymidine (AZT)
      inhibit HIV reproduction in the MT-4 cell line as well as AZT. However, the
      viability of HIV-infected MT-4 cells after treatment with phosphonates was
      considerable higher that after AZT treatment. Inhibitory activities of 5'
      phosphonates of 3'-fluoro-2',3'-dideoxythymidine (FLT) on HIV-infected MT-4 cells
      were rather low. The mechanism of action of these derivatives and prospects for
      their application for suppressing HIV infection are discussed.

PMID- 8145742
TI  - [Preparation of a mutant human tumor necrosis factor with increased resistance to
      proteases].
AB  - The potential proteolysis sites of human TNF are considered. By site-directed
      mutagenesis the Arg-31 residue of mature TNF was substituted by Gln. The analysis
      of cytotoxicity of initial and mutant (R31Q) proteins on mouse L929 fibroblasts
      did not reveal any differences in biological activity. For the mutant protein a
      change in proteolysis dynamics was shown in contrast to the natural variant:
      mutant TNF displayed increased stability when treated with trypsin.

PMID- 8145743
TI  - [Study of the biogenesis and secretion of alkaline phosphatase and its mutant
      forms in Escherichia coli. I. Introduction of directed mutations into the
      alkaline phosphatase gene].
AB  - Various mutations in E. coli alkaline phosphatase gene were obtained by
      oligonucleotide-directed mutagenesis. They result in amino acid substitutions in
      the signal peptide cleavage site [Val for Ala(-1)] and in the N terminus of
      mature polypeptide chain: Ala for Arg(+1) and Gln for Glu(+4); Gln for Glu(+4).
      Enzyme activity was observed in all E. coli strains transformed by plasmids with
      cloned mutant genes. In addition, an amber mutation was introduced into the
      Arg(+1) position, and the synthesis of mutant alkaline phosphatase was shown in
      E. coli strains containing suppressor tRNAs specific for Ser, Gln, Tyr, Leu, Ala,
      Glu, Phe, Gly, His, Pro, and Cys.

PMID- 8145744
TI  - [Design of recombinant plasmids for effective Zymomonas mobilis pyruvate
      decarboxylase (pdk) gene expression in Bacillus subtilis cells].
AB  - The pdk gene from Z. mobilis localized on the 4.7-kb SpHI DNA fragment in plasmid
      pB201 was subcloned using DraI restriction endonuclease into the SmaI site of the
      phage cloning vector M13mp19. The derivatives of M13mp19 obtained, containing 1.8
      kb inserts of the pdk gene in two opposite orientations, were used for DNA
      sequencing and site-directed mutagenesis. The latter was performed using
      polymerase chain reaction (PCR) and synthetic deoxyribonucleotides of appropriate
      structure as primers. In this way a BamHI site near the initial
      (formylmethionine) codon of the pdk gene was created. After amplification the pdk
      gene was treated by restriction endonuclease BamHI and cloned into pUC19, and
      then recloned into shuttle vector pCB20 capable of replicating in both Gram
      negative and Gram positive bacteria. A recombinant plasmid pCB20pdkI--a
      derivative of pCB20 carrying the pdk gene under control of the "expression unit"
      EU19035 containing a bacillar vegetative promoter and an RBS site was obtained.
      The properties of the pCB20pdkI in E. coli and Bac. subtilis cells were studied.
      It was shown that pCB20pdkI determines a high level of PDK synthesis in Bac.
      subtilis. At the same time, it strongly inhibits E. coli cell growth and
      segregates rapidly from this host.

PMID- 8145745
TI  - [The effect of benz(a)pyrene on the thermal characteristics of DNA in vivo and in
      vitro].
AB  - Thermal properties of DNA-benz(a)pyrene complex and chromatin within liver cells
      in BALB/c mice and Macaca fascicularis monkeys after benz(a)pyrene administration
      were studied using a highly sensitive differential scanning microcalorimeter
      designed for investigations of dilute biopolymer solutions and complex biological
      systems. It was shown that benz(a)pyrene (BP) had different efforts on DNA in
      vivo and in vitro. It was established that at a molar ratio r < 0.03 BP/DNA bp,
      benz(a)pyrene served as a stabilizing but at higher concentrations as a
      destabilizing factor of DNA. It was found that BP damaged liver DNA stronger than
      bone marrow and spleen DNA of a given animal in vivo. Based on analysis of heat
      redistribution at the heat absorption stages corresponding to denaturation of
      inactive and active chromatin, we concluded that BP is capable of causing
      specific breaks in the DNA chain of inactive chromatin and unfolding the whole
      domain-loop of chromatin, which should lead to uncontrolled genome activation
      and, therefore, to carcinogenesis.

PMID- 8145746
TI  - [Gene expression in normal and virally transformed erythroid cells and the effect
      of stress factors].
AB  - The globin gene expression in normal and Rauscher virus-transformed murine
      erythroid cells and the effect of heatshock and cycloheximide (CHI) were
      investigated. The hybridization analysis of RNA transcripts synthesized using
      erythroid cell chromatin as a template with globin cDNA demonstrated the
      disturbance of globin gene transcription in transformed erythroblasts. Using the
      Northern hybridization analysis of poly(A) +RNA with pCR1 beta MG9 as a probe,
      the presence of a rather broad RNA set (from approximately 1500 to 450
      nucleotides) in these cells was discovered, while hemoglobin was not synthesized.
      This indicated that the processing of globin mRNA was probably also disturbed. As
      a result of heatshock, the RNA set approached that in normal erythroid cells (500
      650 nucleotides), and the proteins corresponding to globins were synthesized. The
      stable appearance of low molecular weight proteins and the irregular synthesis of
      HSP-90 and HSP-70 in response to heat shock were the characteristic features of
      transformed erythroblasts. After CHI treatment, the content of globin sequences
      in RNA of transformed erythroblasts increased and beta-globin protein chains
      appeared.

PMID- 8145747
TI  - [Uniparametric analysis of chromosomes from human fibroblasts using flow
      cytofluorometry].
AB  - Metaphase chromosomes from human diploid fibroblasts were isolated by the
      polyamine method and stained with different fluorochromes: propidium iodide,
      chromomycine A2, bisbensimide H33258, and DAPI. The fluorescently stained
      chromosomes were analyzed using a cell sorter ATC-3000 ("Bruker-Spectrospine"),
      and the flow histograms were investigated to identify the peaks of individual
      chromosomes and to choose the chromosomes which can be isolated to a high purity.
      High resolution was obtained with H33258 or DAPI. It was demonstrated that the
      peaks of chromosomes 13, 17, 20 are well distinguished from the adjacent peaks,
      so that these chromosomes can be sorted with a high purity. The peaks formed by
      chromosomes 5, 6, 8, 14, 15 are slightly overlapped by the adjacent peaks, and
      the sorting on the basis of monovariate analysis cannot provide sufficient purity
      of the sorted fractions (< 0.5). Chromosomes 1-2, 3-4, 7-X, 9-12, 16-18, 19, 21
      22 cannot be discriminated for successful sorting of an individual chromosome
      type. The data obtained provided an experimental basis for choosing the
      chromosomes to be sorted with high purity for the subsequent cloning of their
      DNA.

PMID- 8145748
TI  - [A compressed form for presenting data to banks on the primary and spatial
      structure of biopolymers. Means for accessing compressed data banks].
AB  - Description of open CAN format (Compressed Amino acids and Nucleotides) is
      presented for storing genetic information in compressed form in data banks (DB).
      Data compression principles are demonstrated in detail on examples of EMBL DB
      (sequences of nucleotides), SWISSPROT DB (sequences of amino acids) and PDB DB
      (3D structures). A unified compressed data format provides a possibility to
      integrate EMBL, SWISSPROT, and PDB DB in one data bank. We are going to use this
      approach for integration of GENBANK and other similar DBs. One of the outcomes of
      the research is a library of data retrieval procedures for access to DB,
      providing developers of the application software packages with a uniform
      interface to DBs with biologically related data. The proposed scheme for data
      representation was recommended by the Expert Commission of the Informatics
      Section of the RSSIP "Human Genome" as a standard for distribution of data banks
      in Russia.

PMID- 8145749
TI  - [Determination of unique peptide fragments in nerve growth factors].
AB  - A new classificational method based on the availability of peptide fragments
      unique for a certain protein family is presented. Seven common peptide fragments
      unique for the nerve growth factor amino acid sequence are determined, and two of
      them are found in the neurotrophic factor from pig brain.

PMID- 8145750
TI  - [Nucleotide sequence of internal transcribed spacers and 5.8S rDNA for the
      ribosomal operon from alfalfa Medicago sativa and cotton Gossypium hirsutum L].
AB  - The 708- and 769-bp fragments from alfalfa and cotton containing the 3'-end of
      the 18S gene, the internal transcribed spacer. 1 (ITS1) the 5.8S gene, ITS2, and
      the 5'-end of the 28S gene were obtained using primers to the 18S and 28S ends of
      rDNA from tomato by a polymerase chain reaction. These sequences were cloned into
      pTZ19R. The 5.8S rDNA, ITS1 and ITS2 nucleotide sequences of alfalfa and cotton
      were determined. Comparative analysis of nucleotide sequences of alfalfa and
      cotton showed large hypervariability of spacer regions and conservatism of 5.8S
      rDNA sequence.

PMID- 8145751
TI  - [Enzymatic DNA methylation as an aging mechanism].
AB  - By analysis of 70 functional parameters of organism it has been shown that the
      senescence of human organs starts from the age of 20 +/- 10 years and it has more
      or less a linear character in the most cases. Judging by the averaged aging rate,
      human maximal lifespan can be equal to about 145 years. An aging model has been
      proposed according to it the functional involution is caused by cells destructing
      and is a result of gradual accumulation of special mutations in genome. The
      evidences has been obtained that enzymatic DNA methylation is a powerful
      generator for the 5mC-->T+C transition, constantly occurring with each cell
      division. It has been found that the age-related loss of the most part or all 5mC
      residues from DNA coincides with both the Hayflick limit in cell lines and the
      maximal lifespan of different animal species studied. The rate of DNA
      hypomethylation is proportional to the cell aging rate in vitro and in vivo. The
      5mC-->T transitions contribute more than half of all point mutations, accumulated
      in genome of vertebrates during evolution. These substitutions occur ten times
      more often in the methylated sites than in other positions of DNA and they
      disproportional contribute to the general mutagenesis and to the hereditary human
      diseases. The conclusion has been made that DNA methylation meet the requirements
      of the main criterions of an aging biomarker and it can be considered as a
      mechanism for genetically programmed accumulation of mutations with aging. In
      immortal cell lines this mechanism starts working in the reverse direction,
      increasing the 5mC content in DNA.

PMID- 8145753
TI  - [Ribonucleoside and 2'-deoxyribonucleoside 5'-phosphonates: synthesis and
      antiviral activity].
AB  - Groups of 5'-phosphonates of natural 2'-deoxynucleosides and ribonucleosides were
      synthesized by condensation of 3'-acetylated 2'-deoxynucleosides or 2',3'
      substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene, or 2',3'-O
      ethoxymethylene) ribonucleosides. As condensing agents, either N,N'
      dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were
      used. Nucleoside 5'-ethoxycarbonyl-phosphonates were converted into corresponding
      nucleoside 5'-aminocarbonylphosphonates by the action of ammonia in methanol. All
      compounds were tested for inhibition of several viruses, including human herpes
      simplex virus type 2 and cytomegalovirus, but showed no activity. A few compounds
      insignificantly inhibited human immunodeficiency virus type 1 reproduction.
      Thymidine 5'-hydrogenphosphonate neutralized the anti HIV action of 3'-azido-3'
      deoxythymidine, thus indirectly showing that it could be partly hydrolyzed in
      cell culture to corresponding thymidine.

PMID- 8145752
TI  - [Connection of polymorphic alleles of the gene cluster AI/CIII/AIV with disturbed
      lipid metabolism].
AB  - The study of polymorphisms of human apolipoprotein AI/CIII/IV gene cluster in the
      Moscow population was carried out using of methods of polymerase chain reaction
      and restriction. Polymorphisms of apolipoprotein AI/CIII/AIV gene cluster
      detected with SacI, PstI, PvuII, MspI have been investigated to search for their
      possible relation to the following quantitative lipid parameters: total
      cholesterol, HDL cholesterol, triglycerides, apolipoproteins AI, apolipoproteins
      B. It has been determined that in groups of individuals with increased
      cholesterol level the frequencies of uncommon alleles at the MspI, SacI, PvuII
      sites were significantly higher than in controls. Our results show that in groups
      with increased triglyceride level the frequency of uncommon alleles at the MspI
      and SacI sites was higher than in controls. Individuals with elevated
      apolipoprotein B and ratio of apolipoproteins B/AI > 1 have significantly higher
      frequency of uncommon alleles at the SacI and PvuII sites and uncommon alleles at
      the PvuII site, respectively. There was no statistically significant correlation
      between polymorphism at PstI site and lipid level variation. It has been
      established, by constructing DNA haplotypes, that the presence of particular
      haplotypes containing an uncommon allele at the PvuII and SacI sites, PvuII and
      MspI sites, MspI and SacI sites, PvuII and PstI sites, SacI and PstI sites is
      associated with lipid disorders, and may be associated with development of
      atherosclerosis.

PMID- 8145754
TI  - [Search for new products of gene expression in human cardiac muscle.
      Microsequencing of proteins after two-dimensional electrophoresis].
AB  - Proteins of the human heart muscle were studied using modified two-dimensional
      electrophoresis. After separation, proteins were electroblotted onto Immobilon P
      membranes and several protein spots were used for microsequencing analysis. In
      most cases the proteins analyzed have blocked N-terminal amino acids. In order to
      study the primary structure of these proteins, hydrolysis in situ by trypsin
      followed by reversed-phase HPLC and microsequencing of the resulting peptides
      were performed. Four protein were identified in 8 analyzed fractions,
      specifically myosin light chain 1 (MLCl-V/sB), fatty-acid binding protein (heart
      isoform), alpha (B)-crystallin and alpha-tropomyosin. Amino acid sequences of two
      proteins were not found among human amino acid sequences collected in SWISSPROT
      bank (v. 21).

PMID- 8145755
TI  - [Molecular biological study of the vaccinia virus. V. Study of the intracellular
      localization of the late nonstructural protein 36K].
AB  - Comparative structural analysis of the 36K proteins of vaccinia, ectromelia,
      cowpox and variola viruses revealed that it is conservative among
      Orthopoxviruses. The possible role of this protein was suggested. A study of the
      synthesis kinetics of vaccinia and ectromelia virus 36K proteins established that
      they belong to late proteins. Electron microscopy of infected cells using protein
      A labelled with colloidal gold showed that the 36K protein is located in the
      viroplast and not coupled to virions or any cell organelles.

PMID- 8145756
TI  - [Interaction of deacylated phenylalanyl tRNA from yeasts with Escherichia coli
      ribosomes. The role of the modified nucleotide in codon-anticodon interaction].
AB  - The method of anticodon loop replacement has been used to make derivatives of
      yeast tRNA(Phe)GmAAY with the substitution at the 37 position (tRNA(Phe)GAAA),
      and at both the anticodon (tRNA(Phe)GCAG) and the 37 position. A quantitative
      study of the interaction of various types of yeast deacylated tRNA:
      tRNA(Phe)GmAAY, tRNA(Phe)GAAA, tRNA(Phe)GCAG, and tRNA(Phe)-Y with the P site of
      the 70S ribosome.poly(U) complex was carried out at different Mg2+ concentrations
      and temperatures. The replacement of the Y base on the nonmodified adenosine
      decreases the interaction enthalpy from 39 to 24 kcal/mole, whereas the complete
      removal of the Y base reduces the interaction enthalpy to 16 kcal/mole. The
      replacement of the second letter of the anticodon (A) with cytosine leads to a
      drop in the enthalpy to 6 kcal/mole, which is typical of tRNA interaction with
      the P site in the absence of poly(U). In the absence of poly(U) the affinity of
      tRNA(Phe)-Y for the P site of the 70S ribosome is 5 times lower than the affinity
      of tRNA(Phe)GmAAY and tRNA(Phe)GCAG. Thus, in the ribosome the modified
      nucleotide not only stabilizes the codon-anticodon interaction owing to the
      stacking interaction with the stack of codon-anticodon bases, but also lowers the
      free energy of binding as a result of the interaction of the modified nucleotide
      itself with the hydrophobic center of the P site on the ribosome.

PMID- 8145757
TI  - [Study of the process of chromatin decondensation using low density agar gel
      electrophoresis].
AB  - A method was proposed for analysis of conformational mobility of supranucleosomal
      chromatin organization at different ionic conditions with the help of
      electrophoresis in low-density agarose gels. This simple and highly reproducible
      method yields the results which are in good agreement with the data of other
      traditional approaches. This method offers an alternative to high-speed
      ultracentrifugation for chromatin condensation studies.

PMID- 8145758
TI  - [Study of segments of 23S RNA, important for interaction with elongation factors
      Tu and G using complementary DNA-oligonucleotides].
AB  - Several oligonucleotides complementary to different 23S RNA regions were tested
      in the elongation factor-dependent reactions of the ribosomes. It was found that
      the 1088-1100 and 1127-1140 sequence parts of the 23S RNA (binding regions for
      the L11 protein) are very important for EF-G function. The EF-Tu function is
      markedly less affected by these nucleotides. The probable role of 23S RNA
      function is discussed.

PMID- 8145759
TI  - [Interaction of a synthetic zinc-binding peptide with DNA].
AB  - Synthesis, DNA- and zinc ion-binding activities of the synthetic 23-residue
      peptide, forming a part of the DNA-binding domain of yeast transcription
      activator GAL-4, are reported. In presence of zinc ions considerable changes in
      the shapes of the fluorescence and CD spectra of the peptide are observed. It is
      shown that the peptide forms complexes with zinc ions containing one metal ion
      per peptide molecule with association constants on the order of (1-2) x 10(6) M
      1. Using gel filtration on a TSK-gel column we have shown that in aqueous
      solution at concentrations of 10(-4)-10(-6) M the peptide exists predominantly in
      the dimeric form. Dimerization constants were found to be 5 x 10(6) M-1 and 1.7 x
      10(7) M-1 in the absence and in the presence of zinc ions, respectively. It is
      shown that the peptide binds to DNA. The binding approaches saturation when one
      peptide molecule is bound approximately to five base pairs of DNA. The shapes of
      the titration curves obtained from binding of the peptide to DNA show that the
      peptide can bind to DNA both in the monomeric and self-associated forms (dimer or
      tetramer). Increasing DNA concentration and decreasing the peptide/DNA molar
      ratio lead to a shift in the equilibria between self-associated peptide species
      and monomers toward the formation of monomer peptide complexes.

PMID- 8145760
TI  - [Heterologous expression of functionally active human cytochrome p-450s. II.
      Modeling the metabolism of xenobiotics using Saccharomyces cerevisiae cells,
      expressing cytochrome P-450IIIA4].
AB  - cDNA encoding human cytochrome P-450IIIA4 was modified by the PCR method to
      attain maximum expression in the Saccharomyces cerevisiae cells and then recloned
      in the shuttle vector pYeDP under the control of galactose-sensitive promoter.
      The strain transformed this plasmid synthesized in the galactose-containing
      medium a protein authentic to P-450IIA4 in its spectral properties and enzymatic
      activity. After subcellular fractionation of the yeast the protein was found in
      the microsomal fraction which displayed a reduced-CO spectrum with maximum
      absorption at 448 nm typical of all members of the P-450 family. The microsomes
      from the transformed yeast catalyzed transformation of nifedipine, a specific
      substrate for P-450IIA4. Thus, transgenic yeast have been constructed mimicking
      the catabolic activity of human cytochrome P-450IIIA4.

PMID- 8145761
TI  - Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is
      activated by adrenal androgens and progesterone.
AB  - Structural changes of the androgen receptor (AR) may contribute to the
      development of resistance to endocrine therapy in prostatic carcinoma. We have
      isolated AR cDNA fragments from seven tumor specimens derived from patients with
      advanced metastatic prostatic tumors. In one specimen obtained from a patient who
      failed to respond to endocrine and cytotoxic therapy we have detected a point
      mutation in the hormone-binding domain of the receptor. This AR mutation is a
      guanine-to-adenine transition at nucleotide 2671 that leads to substitution of
      methionine for the wild type valine at position 715. It is a somatic mutation
      because it was not present in the AR genomic DNA fragments isolated from
      prostatic and testicular tissues of the same patient. The mutant AR was recreated
      in an expression vector and transiently expressed in COS-7 and CV-1 cells.
      Hormone-binding assays revealed that the mutant receptor does not differ from the
      wild type receptor in its ability to bind androgen. The dissociation constant for
      the synthetic androgen mibolerone was 3 nM for both receptors. There was also no
      significant difference in binding of other steroids and nonsteroidal
      antiandrogens as revealed by competition binding assays. However, transfection
      experiments to determine the trans-activation potential of the mutant receptor
      produced differences in the action of this receptor compared to the wild type
      receptor. Dihydrotestosterone and the synthetic androgens methyltrienolone
      (R1881) and mibolerone were equally proficient in conferring trans-activation
      activity to both the mutant and wild type receptors. Adrenal androgens such as
      dehydroepiandrosterone and androstenedione, as well as progesterone mediated a
      higher trans-activation through the mutant than through the wild type receptor.
      These data demonstrate that the exchange of a single valine into methionine at
      position 715 in the AR promoters trans-activation not only by testicular but also
      by adrenal androgens and progesterone. This pattern of ligand-dependent trans
      activation may have significance in the process controlling the progression of
      prostatic carcinoma.

PMID- 8145762
TI  - An alternative Pit-1 RNA splicing product reveals modular binding and nonmodular
      transcriptional activities of the POU-specific domain.
AB  - We have identified a form of the pituitary-specific POU protein Pit-1 that
      results from deletion of the POU-specific (POUs) domain by alternative RNA
      splicing. This natural variant of Pit-1 (called delta 4Pit-1) has revealed
      several aspects of the function of the POUs domain. The delta 4Pit-1 protein was
      characterized using a delta 4Pit-1-specific antiserum. Further, selection assays
      of random oligonucleotide pools identified binding site preferences for both wild
      type and delta 4Pit-1. Methylation interference, copper phenanthrolene, and
      missing contact analyses were used to compare the binding characteristics of the
      two forms of Pit-1 on a selected site. DNA binding affinity assays on several DNA
      elements revealed that the POUs domain contains a modular DNA binding activity
      affecting the DNA binding affinity of the entire POU domain on some, but not on
      other, DNA sites. Functional analysis on such DNA elements has revealed that the
      POUs domain is an essential, but nonmodular, component of the Pit-1 trans
      activation domain dependent on its natural context within the Pit-1 protein.

PMID- 8145763
TI  - A novel mouse kidney 3 beta-hydroxysteroid dehydrogenase complementary DNA
      encodes a 3-ketosteroid reductase instead of a 3 beta-hydroxysteroid
      dehydrogenase/delta 5-delta 4-isomerase.
AB  - The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta
      HSD) is essential for the biosynthesis of all steroid hormones. The enzyme
      catalyzes the conversion of delta 5-3 beta-hydroxysteroids to delta 4-3
      ketosteroids. We report the isolation of a novel mouse 3 beta HSD cDNA, 3 beta
      HSD IV, and describe the tissue-specific expression of its mRNA, the enzyme
      characteristics of the 3 beta HSD IV protein, and the structural and functional
      relationships it has to other 3 beta HSD isoforms previously characterized in the
      mouse and rat. The predicted amino acid sequence of mouse 3 beta HSD IV is 77%
      and 73% identical to that of mouse 3 beta HSD I and III, respectively. Comparison
      of the nucleotide and amino acid sequences of the four isoforms characterized to
      date show that 3 beta HSD IV is more distantly related to I, II, and III than
      these three forms are to each other. 3 beta HSD IV mRNA is only expressed in
      mouse kidney. In situ hybridization of mouse kidney indicates that expression is
      found only in the cortex and appears to be associated with the proximal tubules.
      Transiently expressed 3 beta HSD IV protein could not convert the delta 5-3 beta
      hydroxysteroids, pregnenolone or dehydroepiandrosterone, to their respective
      delta 4-3-ketosteroids, progesterone or androstenedione, nor did it have the
      capacity to convert 5 alpha-androstane-3 beta, 17 beta-diol to
      dihydrotestosterone, characteristic enzymatic activities of expressed mouse 3
      beta HSD I and III. 3 beta HSD IV could only catalyze the conversion of
      dihydrotestosterone to 5 alpha-androstanediol in the presence of the cofactor
      NADPH. Thus, 3 beta HSD IV is a 3-ketosteroid reductase rather than a 3 beta
      hydroxysteroid dehydrogenase/isomerase despite its homology to the other members
      of the 3 beta HSD family. Mouse 3 beta HSD IV is functionally and structurally
      most closely related to rat 3 beta HSD III, an isoform expressed predominantly in
      male rat liver.

PMID- 8145764
TI  - Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor
      gene.
AB  - The TSH receptor (TSHr) is one of the most important thyroid differentiation
      markers. The binding of the TSH hormone to its receptor is an essential step in
      the modulation of thyroid function and differentiation. Here we report that the
      thyroid transcription factor 1 (TTF1), a transcription factor essential for
      thyroid-specific gene expression, binds to the TSHr minimal promoter. The
      promoter, when mutated at this binding site, shows a decreased activity in
      thyroid cells. In cotransfection experiments in nonthyroid cells, TTF1 is able to
      trans-activate the TSHr minimal promoter. This finding strengthens the importance
      of TTF1 in the maintenance of thyroid differentiation. The promoters of the main
      thyroid differentiation markers thyroglobulin, thyroperoxidase, and now TSHr, are
      regulated by TTF1.

PMID- 8145765
TI  - Induction of c-fos and c-jun gene expression by phenolic antioxidants.
AB  - We have found that phenolic antioxidants specifically induce expression of the c
      fos and c-jun protooncogenes. After treatment of quiescent human hepatoma HepG2
      cells with butylated hydroxytoluene, butylated hydroxyanisole, or other phenolic
      antoxidants, the levels of c-fos and c-jun mRNAs are substantially increased.
      This response is antioxidant specific, dose dependent, and transient, with
      maximal levels at 3-6 h. The antioxidant-specific induction of c-fos/CAT promoter
      constructs in transient transfections indicates that at least a portion of this
      response is transcriptional. Deletions and point mutations map sequences required
      for the antioxidant response of the c-fos promoter to the serum response element.
      The antioxidant-specific induction of expression directed by a reporter plasmid
      containing four AP-1 sites and the induction of AP-1 DNA-binding activity confirm
      previous results indicating that antioxidant treatment increases AP-1 activity.

PMID- 8145766
TI  - Cloning of the rat progesterone receptor gene 5'-region and identification of two
      functionally distinct promoters.
AB  - To examine some of the molecular mechanisms controlling transcription of the rat
      progesterone receptor (PR) gene, we have cloned and sequenced the 5'-region of
      the gene. Northern blot analyses with a series of probes identified two regions
      where distinct subsets of the multiple PR gene transcripts initiated, suggesting
      the presence of two promoters in the gene. Promoter activities for two gene
      fragments encompassing these regions, -131/+65 (P; distal) and +461/+675 (P';
      proximal), were demonstrated in transient transfection experiments using reporter
      constructs containing the gene fragments linked individually upstream of the
      chloramphenicol acetyltransferase (CAT) gene. Cotransfection of P-CAT or P'-CAT
      constructs containing two upstream GAL4 binding sites into primary cultures of
      rat uterine cells with a vector expressing a GAL4 DNA binding domain-VP16
      activating region fusion protein resulted in a 10-fold increase in CAT activity
      relative to cells transfected with either reporter and a vector expressing only
      the GAL4 DNA binding domain. The estrogen inducibility of the promoter-CAT
      constructs was assessed by transfection into MCF-7 breast cancer cells, which
      contain high levels of estrogen receptor (ER). P'-CAT, but not P-CAT, was induced
      by estradiol (E2; 8-fold). In primary rat uterine cells, which contain lower
      levels of ER, P'-CAT required the addition of one upstream consensus estrogen
      response element (ERE) to be estrogen inducible, whereas P-CAT required the
      addition of two EREs. Point and deletion mutants of the proximal promoter region
      in the P'-CAT reporter, screened in MCF-7 cells, were used to identify a 20-base
      pair fragment (+617/+636) that retained the promoter activity and 50% of the
      estrogen inducibility of P'. This fragment contained an ERE-like sequence
      conserved in 8 of 10 positions relative to the consensus ERE. Two copies of this
      sequence conferred estrogen inducibility (4-fold) when placed upstream of the
      distal promoter in P-CAT. To examine ER-dependent stimulation of the two PR gene
      promoters by cAMP, P-CAT and P'-CAT reporter constructs containing two upstream
      consensus EREs were cotransfected into ER-negative 3T3 cells with an ER
      expression vector. Induction by E2 was greater than 50-fold for both constructs.
      Treatment of the cells with agents that increase intracellular cAMP levels,
      namely cholera toxin plus isobutyl methylxanthine, resulted in CAT activity that
      was 8% and 51% of the E2-stimulated activity for the P and P' constructs,
      respectively.

PMID- 8145767
TI  - Functional domains of human aromatase cytochrome P450 characterized by linear
      alignment and site-directed mutagenesis.
AB  - The relationship of function to structure of aromatase cytochrome P450 (P450arom;
      the product of the CYP19 gene) has been examined by means of sequence alignment
      and site-directed mutagenesis. Comparison has been made between the sequence of
      P450arom and the two soluble bacterial cytochrome P450 isoforms, whose three
      dimensional structure has been determined (P450BM3 and P450cam). From this
      comparison, it appears that although there is a similarity of overall structure
      in cytochromes P450, there is enough significant difference in the regions
      involved in substrate recognition and substrate binding that residues believed to
      be involved, even in the known structures, must be tested. With this in mind, we
      have generated a detailed alignment of P450arom, including the definition of
      putative alpha-helices and beta-sheets based on comparison of the alignments of
      P450BM3 and P450cam, generated from their three-dimensional structure, and have
      made mutations in regions we believe to be involved in substrate recognition at
      the solvent surface and orientation in the heme pocket. We have mutated F116 and
      F134 to determine if they are present in the heme pocket, and Q225 and L228 to
      determine if they are a part of the substrate recognition loop. Although F116E is
      essentially inactive and may be a folding mutant or may inhibit reductase
      binding, F134E is more active than the wild type and may be located in the heme
      pocket facilitating the hydrogen abstraction from C2 of androstenedione.
      Mutations at Q225 and L228 also result in the anticipated changes in the apparent
      Km and maximum velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145768
TI  - Homologous up-regulation of the gonadotropin-releasing hormone receptor in alpha
      T3-1 cells is associated with unchanged receptor messenger RNA (mRNA) levels and
      altered mRNA activity.
AB  - In primary cultures of rat pituitary, GnRH receptor has been reported to up
      regulate when exposed to GnRH. The molecular basis of this regulation could, in
      theory, involve modulation of gene transcription, RNA processing or stability,
      translation, and/or receptor degradation. The role of altered biosynthesis was
      investigated in the mouse gonadotrope cell line, alpha T3-1 cells, by studying
      the homologous up-regulation of GnRH receptor binding, mRNA levels, and mRNA
      activity. After GnRH exposure, ligand binding was performed on alpha T3-1 cell
      membranes. To correlate changes in receptor number and measurements of
      biosynthetic activity, GnRH receptor mRNA levels were quantitated by solution
      hybridization/RNase protection assay and Northern blot analysis, and the capacity
      of RNA from treated cells to direct the synthesis of new receptors (mRNA
      activity) was evaluated using a Xenopus oocyte-based bioassay. GnRH agonist
      radioligand binding assay results showed that exposure of alpha T3-1 cells to 10(
      10) or 10(-8) M GnRH for 20 min induced an approximately 50% increase in the
      number of GnRH receptors, similar to previously reported results in rat pituitary
      primary culture. Despite the increase in receptor number, however, cytosolic and
      total GnRH receptor mRNA levels assayed by solution hybridization/RNase
      protection assay with GnRH receptor cRNA probes and by Northern blot analysis
      were not altered. In contrast to the unchanging mRNA levels, the measurements of
      mRNA activity paralleled the changes observed at the binding level. alpha T3-1
      RNA from treated and control cells were injected into Xenopus oocytes, and the
      GnRH-induced Cl- current was quantified 48 h later by voltage clamp recording of
      the response to GnRH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145769
TI  - Enhanced c-jun activity alters responsiveness to medroxyprogesterone acetate in
      Ishikawa human endometrial carcinoma cells.
AB  - The involvement of altered c-jun activity in medroxyprogesterone acetate (MPA)
      induced growth responses in human endometrial carcinoma cells is examined in this
      paper. Under conditions of MPA-induced growth inhibition, c-jun mRNA and protein
      levels are decreased in Ishikawa cells. This decrease is accompanied by an
      overall decrease in endogenous AP-1 activity in these cells. Only a transient
      decrease in c-jun mRNA level without any effect on endogenous AP-1 activity is
      seen in HEC-50 human endometrial carcinoma cells after MPA treatment. Increased
      expression and activity of c-jun was achieved in Ishikawa cells by transient
      transfection of Rous sarcoma virus (RSV)-c-jun alone or RSV-c-jun plus AP-1
      binding sites (5x-4-beta-phorobol 12-myristate 13-acetate response element
      thymidine kinase-chloramphenicol acetyltransferase), respectively. These
      treatments were accompanied by an increase in cell numbers due to MPA treatment
      in Ishikawa cells. In contrast, MPA treatment of mock-transfected, RSV-jun-B
      transfected, or 5x-4 beta-phorbol 12-myristate 13-acetate response element
      thymidine kinase-chloramphenicol acetyltransferase alone transfected Ishikawa
      cells resulted in the expected decrease in cell numbers. The data presented in
      this paper are consistent with the hypothesis that altered c-jun activity in a
      target cell can alter proliferative responsiveness to MPA and suggest that such a
      mechanism may be associated with resistance to hormonal manipulative therapies
      used in the treatment of both human breast and endometrial cancer.

PMID- 8145770
TI  - A protein kinase C-dependent activity modulates retinoic acid-induced
      transcription.
AB  - The retinoic acid receptors (RARs) and retinoid X receptors, which are members of
      the nuclear receptor family, mediate the effects of vitamin A derivatives on
      cellular growth and differentiation. The protein kinase C isozyme family also
      controls these processes in response to extracellular stimuli. We have
      investigated the relationship between these two signal transducing pathways using
      gene transfer techniques. We show that selective inhibition of protein kinase C
      (PKC) and its depletion by prolonged treatment with 12-O-tetradecanoylphorbol-13
      acetate lead to the loss of ligand-dependent transcription of an RA-inducible
      promoter. The effect of the depletion in cellular PKC could be counteracted by
      overexpression of PKC alpha and is directly correlated to the loss of the DNA
      binding activity of complexes containing the human RAR alpha (hRAR alpha).
      Indirect immunofluorescence studies demonstrated an altered subcellular
      localization of hRAR alpha. However, direct in vitro phosphorylation of hRAR
      alpha by PKC diminished its ability to form heterodimeric or homodimeric
      complexes on a retinoic acid response element, suggesting that the DNA-binding
      capacity of hRAR alpha in intact cells is indirectly controlled by a PKC
      dependent mechanism. Thus our observations establish a functional link between
      the PKC and retinoid pathways, which are generally considered to have
      antagonistic activities on differentiation processes.

PMID- 8145772
TI  - Insulin-resistant MDA-MB231 human breast cancer cells contain a tyrosine kinase
      inhibiting activity.
AB  - In most human breast cancer cell lines, insulin, via its own receptor, stimulates
      cell growth. However, in MDA-MB231 breast cancer cells, insulin at concentration
      as high as 100 nM has no effect on cell growth, although insulin receptors (IRs)
      are overexpressed in these cells (29.1 ng IR/10(6) cells), and IR binding
      characteristics are similar to other breast cancer cell lines. IR tyrosine kinase
      activity is markedly reduced both in intact MDA-MB231 cells and in isolated IRs
      purified on a wheat germ agglutinin affinity column. MDA-MB231 cells contain a
      factor that inhibits both basal and insulin-stimulated IR tyrosine kinase
      activity in a concentration-dependent manner. This inhibitory activity copurifies
      with the IR on insulin-Sepharose affinity chromatography and is also effective
      against the tyrosine kinase activity of the IR-related insulin-like growth factor
      I receptor and the oncoprotein v-abl but is ineffective against c-src tyrosine
      kinase activity. It is possible, therefore, that this tyrosine kinase inhibitor
      plays a role in regulating the mitogenic potential of the IR in some human breast
      cancers.

PMID- 8145771
TI  - Identification of a major up-stream transcription start site for the human
      progonadotropin-releasing hormone gene used in reproductive tissues and cell
      lines.
AB  - Previous studies suggested that GnRH gene transcripts in human tissues may be
      derived from an upstream transcriptional start site in addition to the well
      characterized hypothalamic start site. To resolve this issue we characterized the
      transcriptional start sites of the human GnRH gene in a human placental tumor
      cell line (JEG) and a human breast tumor cell line (MDA). Using primer extension
      and reverse transcription-polymerase chain reaction (RT-PCR) assay, we identified
      a discrete upstream transcriptional start site 579 bases up-stream from the
      hypothalamic site in both JEG and MDA cell lines. The up-stream start site lacks
      the TATA and CAAT elements often present in RNA polymerase-II promoters, but
      contains the sequence GGTCTTGCT located 84 bases 5' to the up-stream start site
      similar to other genes that lack TATA/CAAT boxes. RT-PCR quantitation shows that
      the up-stream start site is the major transcriptional start site, representing
      74% of the cytoplasmic transcripts in JEG cells and 67% in MDA cells. Supporting
      this observation, transfection assay using a human GnRH promoter/luciferase
      reporter gene construct containing only the up-stream transcription start site
      has a higher level of transcriptional activity than the human GnRH
      promoter/luciferase reporter construct containing only the down-stream start
      site. A high relative abundance (approximately 45%) of total GnRH mRNAs were also
      found in the nucleus of both cell lines, which did not appear to be a consequence
      of the nuclear/cytoplasmic fractionation procedure. To determine if this upstream
      start site was used in normal GnRH-expressing human tissues, we analyzed RNA from
      a variety of postmortem/surgical procedure tissue samples. RT-PCR analysis
      together with Southern blot analysis demonstrated the presence of GnRH mRNA in
      human pituitary, cerebral cortex, testes, ovary, and mammary gland for the first
      time as well as verified GnRH gene expression in hypothalamus and placenta. The
      up-stream transcriptional start site is used only in reproductive tissues, such
      as placenta, testes, ovary, and mammary gland, suggesting tissue-specific
      regulation at this site.

PMID- 8145773
TI  - Detection of Chlamydia trachomatis in urine using enzyme immunoassay and DNA
      amplification.
AB  - The suitability of urine specimens for the detection of Chlamydia trachomatis
      infections in men was assessed. Urethral swabs from 301 patients were cultured
      for C. trachomatis, and the results were compared with results obtained from
      Chlamydiazyme. The results of 298 specimens were also compared with results
      obtained from PCR analysis of first-void urine specimens. The sensitivity of
      confirmed Chlamydiazyme analysis was 93% and the specificity was greater than 99%
      compared with culture. The sensitivity of the PCR method was 100% compared with
      culture. Chlamydia trachomatis was detected by PCR in an additional three
      specimens from which C. trachomatis could not be cultured. Urine appears to be an
      appropriate specimen for the detection of C. trachomatis antigens and nucleic
      acids.

PMID- 8145774
TI  - Optimal conditions for detection of human immunodeficiency virus type 1 DNA by
      polymerase chain reaction with nested primers.
AB  - An assessment of optimal conditions for nested primer amplification of low copy
      number target DNA sequences was made using a human immunodeficiency virus type 1
      (HIV-1) model. In this polymerase chain reaction (PCR) strategy, an outer primer
      pair is first used to amplify the target sequence and a fraction of the
      amplification product is further amplified with a pair of inner (nested) primers.
      Several methodological parameters were evaluated, including number of cycles in
      the first and second step of the reaction, proportion of preamplified material to
      be used as the template for the second amplification, concentrations of primers,
      deoxynucleotides, and Taq DNA polymerase in the outer and inner PCR. The two-step
      PCR required minimal amounts of reaction components and was shown to be highly
      flexible, resulting in exquisite and specificity over a wide range of technical
      conditions. Potential drawbacks of this practical and effective amplification
      procedure are also discussed.

PMID- 8145775
TI  - Comparison of urease gene primer sequences for PCR-based amplification assays in
      identifying the gastric pathogen Helicobacter pylori.
AB  - Different genomic DNA samples and primer sequences were evaluated in urease (ure)
      gene-based PCR assays for rapid identification of Helicobacter pylori. Purified
      DNA and heated (boiled) cell lysates of bacterial cultures from gastric biopsies
      were tested with three primer sets for unique internal ureA, ureA+B and ureC
      sequences. The heated-lysates of H. pylori were quick to prepare but more
      frequently gave unexpected variable or negative PCR results than assays performed
      on purified DNA, which were highly specific and reproducible for all three primer
      sets. Results indicated that sensitivity of the assay was linked to the size of
      the amplified target region rather than any particular strain feature, with the
      small 294 bp ureC product providing more accurate assays with heated-lysates of
      H. pylori. We strongly recommend that negative results in any PCR assay should be
      checked on purified DNA to exclude the possibility of a false-negative result.

PMID- 8145777
TI  - Enzymatic DNA amplification (PCR) in the diagnosis of extrapulmonary
      Mycobacterium tuberculosis infection.
AB  - A polymerase chain reaction able to amplify Mycobacterium tuberculosis DNA from
      clinical samples of extra-pulmonary origin is described. The PCR amplified a 294
      base pair DNA fragment spanning positions 5'-782 to 3'-1075 of the 65 kDa M.
      tuberculosis antigen gene. The procedure enables amplification of target DNA at
      quantities as low as 1 pg of purified material and less than 1000 mycobacteria
      present in clinical samples. The reaction amplifies M. tuberculosis DNA as well
      as Mycobacterium bovis BCG DNA. In 34 extra-pulmonary clinical samples studied,
      18 rendered positive results and two false-negative results; compared to
      classical diagnostic procedures, the sensitivity was 90% and specificity 100%.
      The PCR approach to diagnosis of tuberculosis of extra-pulmonary origin is a
      valid diagnostic alternative to classical procedures.

PMID- 8145776
TI  - Microplate capture hybridization of amplified parvovirus B19 DNA fragment
      labelled with digoxigenin.
AB  - A capture hybridization technique in microplate has been developed for the
      identification of polymerase chain reaction (PCR) amplified B19 DNA fragment in
      clinical specimens. The amplified 104 bp B19 DNA fragment, located in the gene
      coding for structural proteins, was directly labelled during the amplification
      reaction by incorporation of digoxigenin-labelled dUTP. The amplified product was
      then captured by a probe immobilized on microplate wells. The capture
      hybridization reaction was visualized as an enzyme-linked immunosorbent assay
      using anti-digoxigenin Fab fragment labelled with peroxidase. Thirty-five serum
      samples were tested by our capture hybridization assay and the results were in
      accordance with the results obtained by Southern blot analysis of PCR amplified
      product. Our microplate capture hybridization assay showed a high sensitivity and
      reproducibility and appears to be a practical and reliable test for routine
      screening of B19 parvovirus DNA in clinical specimens.

PMID- 8145778
TI  - Oligonucleotide probes complementary to variable regions of 18S rRNA from
      Sarcocystis species.
AB  - Sarcocystis is a large genus of cyst-forming coccidian parasites in the phylum
      Apicomplexa (Protista). Stable RNA was extracted from cystozoites of Sarcocystis
      cruzi, S. tenella, S. fusiformis, S. gigantea and Toxoplasma gondii. The partial
      sequences of the small sub-unit ribosomal RNA (18S rRNA) were determined by
      direct RNA sequencing with reverse transcriptase. The rRNA sequences were
      computer aligned with the published partial sequence of T. gondii, and three
      oligonucleotides complementary to different variable regions of the 18S rRNA were
      synthesized. The three probes were end-labelled with 32P and tested in filter
      hybridization experiments. One of the probes designed to be Sarcocystis genus
      specific, did not cross-hybridize to stable RNA from T. gondii. Two of the probes
      were designed to be species-specific for S. cruzi and S. tenella, and these
      probes hybridized specifically with their respective targets.

PMID- 8145779
TI  - Rapid detection of cytomegalovirus strains resistant to ganciclovir through
      mutations within the gene UL97.
AB  - The human cytomegalovirus (HCMV) gene UL97 product was shown to play an important
      role in phosphorylation of ganciclovir (GCV) in HCMV-infected cells. The deletion
      of the 4 amino-acid sequence AACR confers resistance to a laboratory mutant. The
      aim of this study was to develop a rapid and simple method to detect mutations
      within the 12 base pair (bp) fragment encoding AACR, from isolates and clinical
      specimens (urine, bronchoalveolar lavage, cerebral spinal fluid samples). A
      target region encompassing this 12bp sequence was amplified by a single-step PCR
      assay from HCMV isolates and reference strains, and a two-step procedure from
      clinical specimens. Reaction products were submitted to restriction enzyme
      analysis and dot-blot hybridization assay. Two biotinylated probes were used: one
      probe (DL) overlapping the 12bp region; and a control probe with similar length
      and GC content. Hybridization was performed under conditions allowing the
      detection of one bp deletion (HCMV strain susceptibility to GCV was determined by
      a rapid late antigen synthesis reduction assay.) The control probe hybridized to
      the UL97 sequence amplified from all 23 tested isolates and the reference
      strains. The DL probe gave a positive signal with GCV-susceptible strains; no
      signal was obtained for five out of seven resistant isolates, and for a
      laboratory mutant derived from the strain AD169. Restriction analysis of
      amplification products showed different patterns suggesting this region can be
      involved in various DNA changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145780
TI  - Screening for cystic fibrosis in dried blood spots of newborns.
AB  - We propose a newborn cystic fibrosis (CF) screening test based on the analysis of
      dried blood spot DNA by a strategy involving simple or multiplex denaturing
      gradient gel electrophoresis (DGGE) of PCR products of CFTR gene fragments, in
      conjunction with the immunoreactive-trypsin (IRT) assay. From May 1988 to May
      1992 we have performed a neonatal screening programme of 42,000 newborns in
      Brittany. We identified 450 infants with an elevated IRT level. From this cohort,
      to evaluate the feasibility of measuring IRT in conjunction with mutation
      analysis in Guthrie cards, a pilot study was initially conducted on 200
      individuals with normal IRT and 150 with raised IRT levels. Furthermore, a
      retrospective study was performed on 189 IRT positive cards, involving mutation
      scanning of exons 10 and 11 of the CFTR gene, which contains a number of frequent
      mutations including the deletion delta F508. We show that this approach has
      several implications for neonatal CF screening especially in decreasing the
      recall rate and detecting CF carriers.

PMID- 8145781
TI  - Helicobacter pylori infection and gastric lymphoma.
AB  - BACKGROUND: Helicobacter pylori infection is a risk factor for gastric
      adenocarcinoma. We examined whether this infection is also a risk factor for
      primary gastric non-Hodgkin's lymphoma. METHODS: This nested case-control study
      involved two large cohorts (230,593 participants). Serum had been collected from
      cohort members and stored, and all subjects were followed for cancer. Thirty
      three patients with gastric non-Hodgkin's lymphoma were identified, and each was
      matched to four controls according to cohort, age, sex, and date of serum
      collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma
      from one of the cohorts were evaluated, each of whom had been previously matched
      to 2 controls. Pathological reports and specimens were reviewed to confirm the
      histologic type of the tumor. Serum samples from all subjects were tested for H.
      pylori IgG by an enzyme-linked immunosorbent assay. RESULTS: Thirty-three cases
      of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum
      collection. Patients with gastric lymphoma were significantly more likely than
      matched controls to have evidence of previous H. pylori infection (matched odds
      ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were
      similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median
      of six years had elapsed between serum collection and the development of disease.
      No association was found between nongastric non-Hodgkin's lymphoma and previous
      H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5
      to 3.0). CONCLUSIONS: Non-Hodgkin's lymphoma affecting the stomach, but not other
      sites, is associated with previous H. pylori infection. A causative role for the
      organism is plausible, but remains unproved.

PMID- 8145782
TI  - Effect of a low-fat diet on the incidence of actinic keratosis.
AB  - BACKGROUND: Actinic keratoses are premalignant lesions and are a sensitive and
      important manifestation of sun-induced skin damage. Studies in animals have shown
      that dietary fat influences the incidence of sun-induced skin cancer, but the
      effect of diet on the incidence of actinic keratosis in humans is not known.
      METHODS: We randomly assigned 76 patients with nonmelanoma skin cancer either to
      continue their usual diet (control group) or to eat a diet with 20 percent of
      total caloric intake as fat (dietary-intervention group). For 24 months, the
      patients were examined for the presence of new actinic keratoses by physicians
      unaware of their assigned diets. RESULTS: At base line, the mean (+/- SD)
      percentage of caloric intake as fat was 40 +/- 4 percent in the control group and
      39 +/- 3 percent in the dietary-intervention group. After 4 months of dietary
      therapy the percentage of calories as fat had decreased to 21 percent in the
      dietary-intervention group, and it remained below this level throughout the 24
      month study period. The percentage of calories as fat in the control group did
      not fall below 36 percent at any time. The cumulative number of new actinic
      keratoses per patient from months 4 through 24 was 10 +/- 13 in the control group
      and 3 +/- 7 in the dietary-intervention group (P = 0.001). CONCLUSIONS: In
      patients with a history of nonmelanoma skin cancer, a low-fat diet reduces the
      incidence of actinic keratosis.

PMID- 8145783
TI  - Images in clinical medicine. Chemotherapy-induced acral erythema.

PMID- 8145784
TI  - A comparison of the educational costs and incomes of physicians and other
      professionals.
AB  - BACKGROUND: Efforts at physician-payment reform in the United States have focused
      largely on the relative incomes of primary care physicians and specialists, who
      more often have procedure-based practices. Comparisons of the incomes of
      physicians and other professional groups have received less attention. METHODS:
      We used standard financial techniques to determine the return on educational
      investment over a working lifetime for five groups of professionals: primary care
      physicians, specialist physicians, dentists, attorneys, and graduates of business
      schools. RESULTS: In current dollars, the difference in the average future hourly
      income between a given professional and a high-school graduate of the same age,
      after educational expenses are subtracted (average hours-adjusted net present
      value of the educational investment) was greatest for specialist physicians and
      attorneys; dentists and businesspeople had intermediate values; and primary care
      physicians had the lowest value. The annual yield on the educational investment
      over a working life (hours-adjusted internal rate of return) was 15.9 percent for
      primary care physicians, as compared with 29.0 percent for businesspeople, 25.4
      percent for attorneys, 20.9 percent for specialist physicians, and 20.7 percent
      for dentists. A sensitivity analysis showed that primary care physicians did less
      well in terms of the return on investment than the other groups even when we
      varied the assumptions in our model widely and that specialist physicians did
      less well than attorneys working in law firms and dental specialists.
      CONCLUSIONS: Students can expect a poorer financial return on their educational
      investment when they choose a career in primary care medicine than when they
      choose a procedure-based medical or surgical specialty, business, the law, or
      dentistry.

PMID- 8145785
TI  - Aspirin as an antiplatelet drug.

PMID- 8145786
TI  - Clinical problem-solving. Half a loaf.

PMID- 8145787
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 18-1994. A 37-year-old woman with interstitial lung disease,
      renal masses, and a previous spontaneous pneumothorax.

PMID- 8145788
TI  - Gastric lymphoma and Helicobacter pylori.

PMID- 8145789
TI  - Money and career choice.

PMID- 8145790
TI  - Transmission of HIV-1 from one child to another.

PMID- 8145791
TI  - Transmission of HIV-1 from one child to another.

PMID- 8145792
TI  - Transmission of HIV-1 from one child to another.

PMID- 8145793
TI  - Correlation of nonspecific antiviral activity with the ability to isolate
      infectious HIV-1 from saliva.

PMID- 8145794
TI  - Rifabutin prophylaxis and uveitis.

PMID- 8145796
TI  - Liver transplantation in hepatitis B.

PMID- 8145795
TI  - Liver transplantation in hepatitis B.

PMID- 8145797
TI  - Acute liver failure.

PMID- 8145798
TI  - Acute liver failure.

PMID- 8145799
TI  - Case 49-1993: cystic fibrosis.

PMID- 8145800
TI  - Training in emergency medicine.

PMID- 8145801
TI  - A letter from Sammy Blum.

PMID- 8145802
TI  - Biochemical studies of some non-conventional sources of proteins. Part 7. Effect
      of detoxification treatments on the nutritional quality of apricot kernels.
AB  - Detoxification of apricot kernels by soaking in distilled water and ammonium
      hydroxide for 30 h at 47 degrees C decreased the total protein, non-protein
      nitrogen, total ash, glucose, sucrose, minerals, non-essential amino acids, polar
      amino acids, acidic amino acids, aromatic amino acids, antinutritional factors,
      hydrocyanic acid, tannins and phytic acid. On the other hand, removal of toxic
      and bitter compounds from apricot kernels increased the relative content of crude
      fibre, starch, total essential amino acids. Higher in-vitro protein digestibility
      and biological value was also observed. Generally, the detoxified apricot kernels
      were nutritionally well balanced. Utilization and incorporation of detoxified
      apricot kernel flours in food products is completely safe from the toxicity point
      of view.

PMID- 8145803
TI  - Investigation on the toxicity of fungi from rootstock snacks.
AB  - Chicken embryo bioassay was used to monitor the toxicity of extracts from
      rootstock snack samples during a 210-day storage period. Results show that the
      relative toxicity values which were initially very low increased significantly as
      from 120th day (when 32% mortality was recorded) up till the last day when 73%
      was obtained. Toxicity of extracts from axenic cultures of 12 fungal species
      isolated from the snack samples was also determined. The strains of Aspergillus
      chevalieri, Rhizopus nigricans and Rhizopus sp investigated were nontoxic. A.
      niger, A. flavus, A. fumigatus, Penicillium chrysogenum, A. parasiticus, P.
      citrinum, A. ochraceus, Fusarium monifilorme and A. candidus were found to be
      toxic in decreasing order of potency as recorded after 30 days of growth at room
      temperature on substrate of 0.90 water activity level. Trends in the moisture
      content levels, pH and the incidence of fungal growth on the snack samples were
      also studied. Results suggest that storage for a period not exceeding 90 days and
      maintenance of safe moisture level would control mould growth and the associated
      mycotoxins in the snack.

PMID- 8145804
TI  - Mathematical models for maximum improvement of in vitro protein digestibility of
      high dietary fibre cookies.
AB  - Via substituting with wheat flour some high dietary fibre cookies were prepared
      (with 6, 12, 18 and 24%) from cereal industry by-products: corn bran (CB), rice
      bran (RB) and barley husk (BH). In vitro protein digestibility assay was used to
      examine the effect of substituting on protein digestibility. The applied
      nonlinear mathematical models indicated a higher determination coefficient
      between experimental and predicted data (R2 > or = 0.999). A maximum in vitro
      protein digestibility (IVPD) of 88.4, 84.1, 85.2% was obtained when using optimum
      level substituting with wheat flour (7.9, 9.3 or 5.2%) in the CB, RB or BH
      respectively for producing cookies. The maximum improvement or minimum reducing
      IVPD by using fibre sources in producing cookies ranged from -0.25% in RB to 4.9%
      in CB.

PMID- 8145805
TI  - Health reform: reality strikes USA.

PMID- 8145806
TI  - Health reform: ... as UK faces the bill.

PMID- 8145807
TI  - British beef again.

PMID- 8145809
TI  - UK 'must pay up' for costs of hospital merger.

PMID- 8145808
TI  - French geneticists split over terms of commercial use of DNA bank.

PMID- 8145810
TI  - Biotechnology alliances set to double.

PMID- 8145812
TI  - Health reforms 'could hit biotech companies'.

PMID- 8145811
TI  - Germany uses BSE fears to seek ban on British beef.

PMID- 8145813
TI  - HIV in Zambia: myth or monster?
AB  - Despite attempts by a few journalists to portray the spread of AIDS in African
      countries as fictitious, the situation in Zambia shows that such views are
      completely misguided.

PMID- 8145814
TI  - Psychology. Beauty and the beholder.

PMID- 8145815
TI  - Developmental biology. Unanimity waits in the wings.

PMID- 8145816
TI  - Neurobiology. Tracking neurotrophin function.

PMID- 8145817
TI  - Cerebral asymmetry and handedness.

PMID- 8145818
TI  - Compartment boundaries and the control of Drosophila limb pattern by hedgehog
      protein.
AB  - Drosophila limbs are subdivided into anterior and posterior compartments which
      derive from adjacent cell populations founded early in development. Evidence is
      now provided that posterior cells organize growth and cell patterning in both
      compartments by secreting hedgehog protein and that hedgehog protein acts
      indirectly by inducing neighbouring anterior cells to secrete decapentaplegic or
      wingless protein.

PMID- 8145819
TI  - Crystal structure of the human class II MHC protein HLA-DR1 complexed with an
      influenza virus peptide.
AB  - An influenza virus peptide binds to HLA-DR1 in an extended conformation with a
      pronounced twist. Thirty-five per cent of the peptide surface is accessible to
      solvent and potentially available for interaction with the antigen receptor on T
      cells. Pockets in the peptide-binding site accommodate five of the thirteen side
      chains of the bound peptide, and explain the peptide specificity of HLA-DR1.
      Twelve hydrogen bonds between conserved HLA-DR1 residues and the main chain of
      the peptide provide a universal mode of peptide binding, distinct from the
      strategy used by class I histocompatibility proteins.

PMID- 8145820
TI  - The curvature elastic-energy function of the lipid-water cubic mesophase.
AB  - Cell and lipid membranes are able to bend, as manifested during membrane fusion
      and the formation of non-lamellar lyotropic mesophases in water. But there is an
      energy cost to bending of lipid layers, called the curvature elastic energy.
      Although the functional form of this energy is known, a complete quantitative
      knowledge of the curvature elastic energy, which is central to predicting the
      relative stability of the large number of phases that lipid membranes can adopt,
      has been lacking. Here we use X-ray synchrotron diffraction measurements of the
      variation of lattice parameter with pressure and temperature for the periodic
      Ia3d (Q230) cubic phase of hydrated monoolein to calculate the complete curvature
      elastic-energy function for the lipid cubic mesophase. This allows us to predict
      the stabilities of different cubic and lamellar phases for this system as a
      function of composition.

PMID- 8145821
TI  - Direct imaging of reptation for semiflexible actin filaments.
AB  - According to the reptation model of polymer diffusion, a polymer chain exhibits
      snake-like motion through the entangled mesh of surrounding molecules, in which
      the undulations of the chain are restricted to a tube-like region. The reptation
      model can account for many of the dynamic properties of entangled polymer
      solutions and melts, and has received support from observations of block
      copolymer diffusion across an interface; but reptative motion has not previously
      been imaged directly. Here we report such a direct observation of reptation,
      obtained by video microscopy of fluorescently labelled single, semiflexible
      filaments of actin in a solution of unlabelled actin filaments. From the
      restricted thermal undulations of these filaments we can measure the diameter of
      the confining tube, and we also observe the characteristic thermally excited
      sliding of the filament out of the end of the tube. We find that the chain self
      diffusion coefficient decreases approximately linearly as the filament length
      increases, in agreement with the reptation model.

PMID- 8145822
TI  - Facial shape and judgements of female attractiveness.
AB  - The finding that photographic and digital composites (blends) of faces are
      considered to be attractive has led to the claim that attractiveness is
      averageness. This would encourage stabilizing selection, favouring phenotypes
      with an average facial structure. The 'averageness hypothesis' would account for
      the low distinctiveness of attractive faces but is difficult to reconcile with
      the finding that some facial measurements correlate with attractiveness. An
      average face shape is attractive but may not be optimally attractive. Human
      preferences may exert directional selection pressures, as with the phenomena of
      optimal outbreeding and sexual selection for extreme characteristics. Using
      composite faces, we show here that, contrary to the averageness hypothesis, the
      mean shape of a set of attractive faces is preferred to the mean shape of the
      sample from which the faces were selected. In addition, attractive composites can
      be made more attractive by exaggerating the shape differences from the sample
      mean. Japanese and caucasian observers showed the same direction of preferences
      for the same facial composites, suggesting that aesthetic judgements of face
      shape are similar across different cultural backgrounds. Our finding that highly
      attractive facial configurations are not average shows that preferences could
      exert a directional selection pressure on the evolution of human face shape.

PMID- 8145823
TI  - Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF
      receptor gene.
AB  - Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of
      embryonic sensory and sympathetic neurons in culture. In vivo, NGF decreases the
      extent of naturally occurring cell death in developing sympathetic ganglia and
      protects cholinergic neurons of the basal forebrain and caudatoputamen. NGF
      interacts with the low-affinity p75 receptor and with Trk, a receptor tyrosine
      kinase encoded by the trk proto-oncogene. To study the role of Trk in vivo, we
      have ablated the gene in embryonic stem cells by homologous recombination. Mice
      lacking Trk have severe sensory and sympathetic neuropathies and most die within
      one month of birth. They have extensive neuronal cell loss in trigeminal,
      sympathetic and dorsal root ganglia, as well as a decrease in the cholinergic
      basal forebrain projections to the hippocampus and cortex. These findings
      demonstrate that Trk is the primary mediator of the trophic actions of NGF in
      vivo and that this signalling pathway plays a crucial role in the development of
      both the peripheral and the central nervous systems.

PMID- 8145824
TI  - Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle
      afferents and results in abnormal movements.
AB  - The trkC gene is expressed throughout the mammalian nervous system and encodes a
      series of tyrosine protein kinase isoforms that serve as receptors for
      neurotrophin-3 (NT3), a member of the nerve growth factor (NGF) family of
      neurotrophic factors. One of these isoforms, gp145trkC/TrkC K1, mediates the
      trophic properties of NT3 in cultured cells. Here we show that homozygous mice
      defective for TrkC tyrosine protein kinase receptors lack Ia muscle afferent
      projections to spinal motor neurons and have fewer large myelinated axons in the
      dorsal root and posterior columns of the spinal cord. These mice display abnormal
      movements and postures, indicating that NT3/TrkC-dependent sensor; neurons may
      play a primary role in proprioception, the sense of position and movement of the
      limbs.

PMID- 8145825
TI  - Co-evolution of ligand-receptor pairs.
AB  - Specific receptors for lutropin (luteinizing hormone; LH) and follitropin
      (follicle-stimulating hormone; FSH) mediate the actions of human chorionic
      gonadotropin (hCG) and FSH5 on the gonads. Here we report that short independent
      sequences of the beta-subunit enable hCG to distinguish between the receptors for
      FSH and LH. Residues between the 11th and 12th cysteines restrict FSH receptor
      binding; residues between the 10th and 11th cysteines and, to a much lesser
      extent, residues carboxy-terminal to the 12th cysteine also affect LH receptor
      binding. CF101-109, an hCG analogue containing hFSH beta residues between the
      11th and 12th cysteines, had high affinity for both LH and FSH receptors.
      Modifications to CF101-109 that reduce binding to either LH or FSH receptors
      yield gonadotropin analogues having differing ratios of LH:FSH activity. Ligand
      binding specificity of the LH receptor is determined by residues encoded by parts
      of exons 2-4 and 7-9 which prevent hFSH binding but have little effect on hCG
      binding. FSH receptor specificity is controlled primarily by residues encoded by
      exons 5 and 6 that prevent hCG binding but have little effect on hFSH binding.
      These determinants can be interchanged to create receptor analogues that bind hCG
      and hFSH. Our observations support a model in which distinct negative
      determinants restrict ligand-receptor interaction. This explains coevolution of
      binding specificity in families of homologous ligands and their receptors.
      Natural or designed manipulation of these determinants leads to the 'evolution'
      of new, specific protein-protein interactions.

PMID- 8145826
TI  - Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial
      potassium channel.
AB  - Acetylcholine activates inwardly rectifying potassium channels (IK.ACh) in the
      heart through muscarinic receptor binding and activation of pertussis-toxin
      sensitive G proteins. Experiments showing that only the beta gamma-subunit (G
      beta gamma) activates IK.ACh (ref. 4) were challenged by reports that only the
      activated alpha-subunit (G alpha) was effective. Here we examine IK.ACh
      regulation using purified brain and recombinant G-protein subunits. Six
      recombinant G beta gamma-subunits activated IK.ACh with apparent half-maximal
      activation concentrations of 3-30 nM. Activation of IK.ACh by recombinant G alpha
      GTP gamma S was observed, but this was probably due to release of GTP gamma S
      from the protein. Importantly, IK.ACh activity elicited by GTP gamma S was
      inhibited by purified brain and recombinant G alpha-GDP, suggesting that native G
      beta gamma plays a major role in this pathway. We conclude that G beta gamma is a
      primary regulator of IK.ACh activity.

PMID- 8145827
TI  - Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with
      hereditary non-polyposis colon cancer.
AB  - The human DNA mismatch repair gene homologue hMSH2, on chromosome 2p is involved
      in hereditary non-polyposis colon cancer (HNPCC). On the basis of linkage data, a
      second HNPCC locus was assigned to chromosome 3p21-23 (ref. 3). Here we report
      that a human gene encoding a protein, hMLH1 (human MutL homologue), homologous to
      the bacterial DNA mismatch repair protein MutL, is located on human chromosome
      3p21.3-23. We propose that hMLH1 is the HNPCC gene located on 3p because of the
      similarity of the hMLH1 gene product to the yeast DNA mismatch repair protein,
      MLH1, the coincident location of the hMLH1 gene and the HNPCC locus on chromosome
      3, and hMLH1 missense mutations in affected individuals from a chromosome 3
      linked HNPCC family.

PMID- 8145828
TI  - Multi-target PCR analysis by capillary electrophoresis and laser-induced
      fluorescence.
AB  - Quantitative analysis of polymerase chain reaction (PCR) amplified HIV-1 DNA or
      cDNA fragments is attained using an automated system that combines capillary-gel
      electrophoresis (CGE) for high-efficiency separation and laser-induced
      fluorescence (LIF) for high-sensitivity detection. This system enables the
      detection of PCR-amplified multiple target DNA or cDNA in the same tube by a
      single injection with high precision.

PMID- 8145829
TI  - Patents for eugenics.

PMID- 8145830
TI  - Genetically altered tomato set to get the green light.

PMID- 8145831
TI  - French lab drops US deal over access to DNA bank.

PMID- 8145832
TI  - Newspaper revives anti-HIV claims.

PMID- 8145833
TI  - Study confirms AZT's lack of prophylactic effect [new].

PMID- 8145834
TI  - In the eye of the beholder?

PMID- 8145835
TI  - Undue credit for supervisors.

PMID- 8145836
TI  - Delaney and cancer.

PMID- 8145837
TI  - Descent to tabloid Nature?

PMID- 8145838
TI  - Italy's contribution to EMBL.

PMID- 8145839
TI  - Don't eat it.

PMID- 8145840
TI  - Change the rules for food additives.
AB  - The Delaney clause, embodied in US legislation in 1958, prohibits the addition to
      food of any level of any carcinogen. This position cannot be sustained in the
      face of progress in understanding chemically induced cancer.

PMID- 8145841
TI  - Primate palaeontology. Bonanza at Shanghuang.

PMID- 8145842
TI  - Sensory maps in the human brain.

PMID- 8145843
TI  - New mammals not so seldom.

PMID- 8145844
TI  - Skin cancer and ultraviolet.

PMID- 8145845
TI  - A diverse new primate fauna from middle Eocene fissure-fillings in southeastern
      China.
AB  - We report the discovery of a fauna of primates from Eocene (approximately 45 Myr)
      deposits in China having a diversity greater than in European and North American
      localities of similar antiquity. From the many forms that will illuminate
      questions of primate phylogeny comes evidence for a basal radiation of primitive
      simians.

PMID- 8145846
TI  - Avalanches and power-law behaviour in lung inflation.
AB  - When lungs are emptied during exhalation, peripheral airways close up. For people
      with lung disease, they may not reopen for a significant portion of inhalation,
      impairing gas exchange. A knowledge of the mechanisms that govern reinflation of
      collapsed regions of lungs is therefore central to the development of ventilation
      strategies for combating respiratory problems. Here we report measurements of the
      terminal airway resistance, Rt, during the opening of isolated dog lungs. When
      inflated by a constant flow, Rt decreases in discrete jumps. We find that the
      probability distribution of the sizes of the jumps and of the time intervals
      between them exhibit power-law behaviour over two decades. We develop a model of
      the inflation process in which 'avalanches' of airway openings are seen--with
      power-law distributions of both the size of avalanches and the time intervals
      between them--which agree quantitatively with those seen experimentally, and are
      reminiscent of the power-law behaviour observed for self-organized critical
      systems. Thus power-law distributions, arising from avalanches associated with
      threshold phenomena propagating down a branching tree structure, appear to govern
      the recruitment of terminal airspaces.

PMID- 8145848
TI  - Sympatric speciation suggested by monophyly of crater lake cichlids.
AB  - The existence of sympatric speciation--that populations diverge into species in
      the absence of physical or ecological barriers--is controversial. The East
      African Great Lakes harbour hundreds of cichlid species representing only a few
      monophyletic lineages, although palaeolimnological evidence and local
      restrictions on species distribution suggest that speciation in these lakes could
      have been allopatric. The case for sympatry in restricted areas of Lakes Malawi
      and Tanganyika is stronger but not unassailable. A better case might be made for
      cichlid species flocks in small, ecologically monotonous crater lakes. Here we
      present a mitochondrial DNA analysis of cichlid species flocks endemic to two
      such lakes in Cameroon. The results suggest that the flocks in each lake are
      monophyletic: the implication being that each lake was colonized once only, the
      size and shape of each lake being such that subsequent diversification would have
      been sympatric.

PMID- 8145847
TI  - Metabolism of polyhalogenated compounds by a genetically engineered bacterium.
AB  - The decomposition of organic compounds by bacteria has been studied for almost a
      century, during which time selective enrichment culture has generated
      microorganisms capable of metabolizing thousands of organic compounds. But
      attempts to obtain pure cultures of bacteria that can metabolize highly
      halogenated compounds, a large and important class of pollutants, have been
      largely unsuccessful. Polyhalogenated compounds are most frequently metabolized
      by anaerobic bacteria as a result of reductive dehalogenation reactions, the
      products of which are typically substrates for bacterial oxygenases. Complete
      metabolism of polyhalogenated compounds therefore necessitates the sequential use
      of anaerobic and aerobic bacteria. Here we combine seven genes encoding two multi
      component oxygenases in a single strain of Pseudomonas which as a result
      metabolizes polyhalogenated compounds by means of sequential reductive and
      oxidative reactions to yield non-toxic products. Cytochrome P450cam monooxygenase
      reduces polyhalogenated compounds, which are bound at the camphor-binding site,
      under subatmospheric oxygen tensions. We find that these reduction products are
      oxidizable substrates for toluene dioxygenase. Perhalogenated chlorofluorocarbons
      also act as substrates for the genetically engineered strain.

PMID- 8145849
TI  - Brain regions associated with acquisition and retrieval of verbal episodic
      memory.
AB  - It is widely held that conscious recall of past experiences involves a specific
      system--episodic memory. Patients with amnesia have gross impairments of episodic
      memory while other kinds of memory remain intact, suggesting that a separable
      brain system underlies episodic memory. We have used positron emission tomography
      (PET) to identify components of this system in normal volunteers. A dual-task
      interference paradigm was used to isolate brain areas associated with
      acquisition, and a cueing paradigm to isolate the areas concerned with retrieval
      from verbal episodic memory. Acquisition was associated with activity in the left
      prefrontal cortex and the retrosplenial area, whereas retrieval was associated
      with activity in right prefrontal cortex and the precuneus. Our results provide
      clear evidence that episodic memory involves a network of specific prefrontal and
      posterior structures which can be fractionated into different component
      processes.

PMID- 8145850
TI  - Limb alterations in brachypodism mice due to mutations in a new member of the TGF
      beta-superfamily.
AB  - The mutation brachypodism (bp) alters the length and number of bones in the limbs
      of mice but spares the axial skeleton. It illustrates the importance of specific
      genes in controlling the morphogenesis of individual skeletal elements in the
      tetrapod limb. We now report the isolation of three new members of the
      transforming growth factor-beta (TGF-beta) superfamily (growth/differentiation
      factors (GDF) 5,6 and 7) and show by mapping, expression patterns and sequencing
      that mutations in Gdf5 are responsible for skeletal alterations in bp mice. GDF5
      and the closely related GDF6 and GDF7 define a new subgroup of factors related to
      known bone- and cartilage-inducing molecules, the bone morphogenetic proteins
      (BMPs). Studies of Bmp5 mutations in short ear mice have shown that at least one
      other BMP gene is also required for normal skeletal development. The highly
      specific skeletal alterations in bp and short ear mice suggest that different
      members of the BMP family control the formation of different morphological
      features in the mammalian skeleton.

PMID- 8145851
TI  - Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic
      stem cells and is encoded by variant RNAs.
AB  - The FLT3/FLK2 receptor tyrosine kinase is closely related to two receptors, c-Kit
      and c-Fms, which function with their respective ligands, Kit ligand and
      macrophage colony-stimulating factor to control differentiation of haematopoietic
      and non-haematopoietic cells. FLT3/FLK2 is thought to be present on
      haematopoietic stem cells and found in brain, placenta and testis. We have
      purified to homogeneity and partially sequenced a soluble form of the FLT3/FLK2
      ligand produced by mouse thymic stromal cells. We isolated several mouse and
      human complementary DNAs that encode polypeptides with identical N termini and
      different C termini. Some variants contain hydrophobic transmembrane segments,
      suggesting that processing may be required to release soluble ligand. The
      purified ligand enhances the response of mouse stem cells and a primitive human
      progenitor cell population to other growth factors such as interleukins IL-3 and
      IL-6 and to granulocyte-macrophage colony-stimulating factor, and also stimulates
      fetal thymocytes.

PMID- 8145852
TI  - Specificity of the thrombin receptor for agonist peptide is defined by its
      extracellular surface.
AB  - G-protein-coupled receptors for catecholamines and some other small ligands are
      activated when agonists bind to the transmembrane region of the receptor. The
      docking interactions through which peptide agonists activate their receptors are
      less well characterized. The thrombin receptor is a specialized peptide receptor.
      It is activated by binding its tethered ligand domain, which is unmasked upon
      receptor cleavage by thrombin. Human and Xenopus thrombin receptor homologues are
      each selectively activated by the agonist peptide representing their respective
      tethered ligand domains. Here we identify receptor domains that confer this
      agonist specificity by replacing the Xenopus receptor's aminoterminal exodomain
      and three extracellular loops with the corresponding human structures. This
      switches receptor specificity from Xenopus to human. The specificity of these
      thrombin receptors for their respective peptide agonists is thus determined by
      their extracellular surfaces. Our results indicate that agonist interaction with
      extracellular domains is important for thrombin receptor activation.

PMID- 8145853
TI  - Calmodulin interacts with amphiphilic peptides composed of all D-amino acids.
AB  - Calmodulin binds to amphiphilic, helical peptides of a variety of amino-acid
      sequences. These peptides are usually positively charged, although there is
      spectroscopic evidence that at least one neutral peptide binds. The complex
      between calmodulin and one of its natural target peptides, the binding site for
      calmodulin on smooth muscle myosin light-chain kinase (RS20), has been
      investigated by crystallography and NMR which have characterized the interactions
      between the ligand and the protein. From these data, it appears that the
      calmodulin-binding surface is sterically malleable and van der Waals forces
      probably dominate the binding. To explore further this apparently permissive
      binding, we investigated the chiral selectivity of calmodulin using synthesized
      analogues of melittin and RS20 that consisted of only D-amino acids. Fluorescence
      and NMR measurements show that D-melittin and D-RS20 both bind avidly to
      calmodulin, probably in the same general binding site as that for peptides having
      all L-amino acids. The calmodulin-peptide binding surface is therefore remarkably
      tolerant sterically. Our results suggest a potentially useful approach to the
      design of non-hydrolysable or slowly hydrolysable intracellular inhibitors of
      calmodulin.

PMID- 8145854
TI  - Structural and kinetic characterization of a beta-lactamase-inhibitor protein.
AB  - The past decade has seen an alarming worldwide increase in resistance to beta
      lactam antibiotics among many pathogenic bacteria, which is due mainly to plasmid
      or chromosomally encoded beta-lactamases that specifically cleave penicillin and
      cephalosporins, rendering them inactive. There is therefore a need to develop new
      strategies in the design of effective inhibitors of beta-lactamase. All the small
      molecule inhibitors in clinical use are not very effective and are rapidly
      degraded. Furthermore, newly characterized mutants of the plasmid-mediated beta
      lactamase TEM-1 are highly resistant to these small-molecule inhibitors,
      including clavulanic acid and tazobactam. It has been shown that Streptomyces
      clavuligerus produces an exocellular beta-lactamase inhibitory protein (BLIP;
      M(r) 17.5 K). Here we present data defining BLIP as the most effective known
      inhibitor of a variety of beta-lactamases, with Ki values in the subnanomolar to
      picomolar range. To identify those features in BLIP that make it such a potent
      inhibitor, we have determined its molecular structure at 2.1 A resolution. BLIP
      is a relatively flat molecule with a unique fold, comprising a tandem repeat of a
      76-amino-acid domain. Each domain consists of a helix-loop-helix motif that packs
      against a four-stranded antiparallel beta-sheet (Fig. 1a). To our knowledge, BLIP
      is the first example of a protein inhibitor having two similarly folded domains
      that interact with and inhibit a single target enzyme.

PMID- 8145855
TI  - Structure of restriction endonuclease BamHI and its relationship to EcoRI.
AB  - Type II restriction endonucleases are characterized by the remarkable specificity
      with which they cleave specific DNA sequences. Surprisingly, their protein
      sequences are in most cases unrelated, and no recurring structural motif has yet
      been identified. We have determined the structure of restriction endonuclease
      BamHI at 1.95 A resolution. BamHI shows striking resemblance to the structure of
      endonuclease EcoRI (refs 3, 4), despite the lack of sequence similarity between
      them. We also observe some curious differences between the two structures, and
      propose an evolutionary scheme that may explain them. The active site of BamHI is
      structurally similar to the active sites of EcoRI and EcoRV (ref. 5), but the
      mechanism by which BamHI activates a water molecule for nucleophilic attack may
      be different.

PMID- 8145856
TI  - Catch and move--cut or fuse.
AB  - Still almost unbelievable, but true: light exerts force. With these forces it is
      indeed possible to catch and move cells or small particles and microsurgically to
      process them without any mechanical contact. As if by magic, objects are moved
      via focused laser light.

PMID- 8145857
TI  - Natural hybridization in freshwater animals. Ecological implications and
      molecular approaches.
AB  - The number of cases where the phenomena of hybridization and gene introgression
      have been found in species interactions is steadily increasing, in both plant and
      animal taxa. During the last few years, many examples have been detected even in
      otherwise well-known freshwater animal taxa. We discuss the topic with respect to
      ecology and evolutionary processes and compare the main potentials and
      limitations of allozymes, mitochondrial DNA, and RAPD markers to address some
      important genetic issues of interspecific hybridization in natural populations of
      selected freshwater model systems.

PMID- 8145858
TI  - [Chromatin structure and gene regulation].
AB  - It is becoming increasingly clear that the nucleosome, the basic repeat unit of
      eukaryotic chromatin, is involved also in gene regulation. In particular, the
      study of inducible genes has shown that nucleosomes contribute to the repressed
      basal state, and that they can be rearranged in response to induction. The role
      of the nucleosomes in gene regulation and possible mechanisms for their
      structural modulation are discussed.

PMID- 8145859
TI  - How do outgrowing electrosensory nerve fibers find their peripheral
      electroreceptor sites?

PMID- 8145860
TI  - [A numb feeling in hand and arm following an operation].

PMID- 8145861
TI  - [Somatization disorder: clinical aspects, diagnosis and treatment].

PMID- 8145862
TI  - [Treatment of hirsutism].

PMID- 8145863
TI  - [The significance of convulsion-like signs in the first 2 years of life].
AB  - OBJECTIVE: Assessment of the prevalence of convulsion-like symptoms in 1854
      children of Dutch-speaking mothers of a population-based birth cohort. METHOD: At
      each child health clinic (CHC) visit mothers were asked whether they had noted
      any of the following signs: loss of consciousness, involuntary movements, eye
      rotation movements and apnoea, and if so, whether these appeared to be related to
      feeding. Registration was done by the CHC physician during eight consultations.
      RESULTS: Convulsion-like symptoms occurred in a quarter of the children: in 8%
      exclusively in relation to feeding, almost without exception in the first three
      months of life, in 19% also without relation to feeding, continuing until the
      second birthday. The latter children were more frequently admitted into hospital,
      even for non-neurological problems, than the former or than children without any
      such signs. They also have more disabilities at the age of two years. No
      connection with epilepsy in the family or with congenital anomalies could be
      demonstrated. CONCLUSION: Convulsion-like symptoms were observed in a quarter of
      children up to the age of two years. Special attention should be paid by the CHC
      team to children with signs not connected with feeding.

PMID- 8145864
TI  - [Aortic valve replacement using aortic donor valves of human origin].
AB  - OBJECTIVE: To evaluate the experiences of aortic valve replacement with
      cryopreserved aortic allografts in the subcoronary position. DESIGN: Descriptive
      clinical study. SETTING: Thorax Centre of Rotterdam University Hospital. METHOD:
      In the period July 1988-March 1993, 68 patients (45 men and 23 women) with a mean
      age of 45 years underwent 69 operations. One woman was operated twice. Main
      criteria for aortic valve replacement by an allograft were age and endocarditis.
      The pathology leading to aortic valve dysfunction had been: endocarditis (38%),
      congenital lesions (32%), rheumatic lesions (19%), senile degeneration (7%),
      paravalvular leakage (3%) and an active autoimmune disease (1%). RESULTS:
      Hospital mortality was 4%. The mean follow-up was 22 months, with a cumulative
      follow-up of 126 patient years. One patient died of lung cancer during this
      period. Six patients needed a second operation (9%); 4 of these were among the
      first 15 patients operated on. One of these reoperations was necessary to treat a
      recurrent endocarditis. Only one other late valve-related event took place: a
      transient ischaemic attack 2 years postoperatively. Ninety-one per cent of the
      patients with an allograft in situ were in NYHA class I at their last outpatient
      clinic visit. The other patients were in class II. Pre-cordial color Doppler
      echocardiography showed no or mild aortic regurgitation in 95% of these patients.
      The remaining 3 patients had moderate aortic regurgitation. CONCLUSION: Aortic
      valve replacement with an allograft was performed with low hospital mortality.
      The expected advantages are greatest in young patients and patients with
      endocarditis; these patients, therefore, should have priority in allograft
      allocation.

PMID- 8145865
TI  - [Potential cornea, heart valve, bone and skin donors in 5 Dutch hospitals far
      outnumber actual donors].
AB  - OBJECTIVE: To determine the number of potential cornea, heart valve, bone and
      skin donors among patients who died in Dutch hospitals, in comparison with the
      number of actual donors. DESIGN: Descriptive. SETTING: Five hospitals in the
      western part of the Netherlands. MATERIAL AND METHODS: The medical records of
      patients who died in 1989 were reviewed. Children younger than 4 weeks were
      excluded from the study. On the basis of criteria used by the Eurotransplant and
      Bio Implant Services Foundations and those of the skin bank of the Dutch Burns
      Foundation, it was determined if the deceased were medically suitable as cornea,
      heart valve, bone or skin donor. RESULTS: Data were collected on 2150 of 2369
      deceased (90.8%), mean age 69.5 (17.0) (SD) years. Medical criteria for cornea
      donation were met in 72% of the cases, 6.8% of these became actual donors. The
      figures for heart value donors were 4.3% and 9.7% respectively, and for bone
      donors 2.7% and 0%. The percentage of potential skin donors could not be
      determined, because essential data were missing from the medical records. After
      extrapolation the number of donors among all patients who died in Dutch hospitals
      in 1989 amounted to 35,046 potential cornea donors, 2,093 potential heart valve
      donors and 1,314 potential bone donors. CONCLUSION: Only a very small proportion
      of the potential tissue donors were referred to Eurotransplant and Bio Implant
      Services. Therefore, waiting lists for tissue transplantation are not necessary.

PMID- 8145866
TI  - [Rapidly progressive aortic insufficiency in a female patient with rheumatoid
      arthritis].
AB  - In a 23-year-old woman with severe rheumatoid arthritis, a rapidly progressive
      aortic regurgitation (onset within 2 years) was observed. She had a high IgM
      rheumatoid factor titre and nailfold lesions. The differential diagnosis from
      infectious endocarditis was difficult. The patient's aortic valve was replaced
      with a St. Jude mechanical prosthesis. The aortic valve was tricuspid with thick
      sclerotic cusps and sterile ulcerations and vegetations on the left and right
      coronary cusps. Histopathologic examination showed hyaline degenerative changes
      and plasma cell infiltrates in the stroma of the cusps, associated with
      rheumatoid arthritis. In the literature, aortic regurgitation is associated with
      longstanding rheumatoid arthritis, subcutaneous nodules, a high IgM rheumatoid
      factor titre and (or) signs of vasculitis.

PMID- 8145867
TI  - [Current composition of oral phenobarbital FNA mixture could lead to
      convulsions].

PMID- 8145868
TI  - [Obstetrical outcome of teenage pregnancies in The Netherlands].

PMID- 8145869
TI  - [Obstetrical outcome of teenage pregnancies in The Netherlands].

PMID- 8145870
TI  - [Melancholia as existential condition].
AB  - Starting from the anthropological understanding and structural analysis of
      melancholia (Minkowski, E. Straus, von Gebsattel, L. Binswanger, Tellenbach), it
      is made an attempt to show historicity of man as significant for existential
      condition. Melancholic patients are basically lacking historical meaning of
      existence.

PMID- 8145871
TI  - [The phenomenology of hysterical personality disorder].
AB  - Phenomena that are observable in the "classic" hysterical personality disorder
      are named, described and classified according to the basic functions of human
      experience and behavior. In this way, a psychopathological picture of the
      hysterical personality arises, which can facilitate the sometimes difficult task
      of diagnosis and differential diagnosis. It is shown that the phenomenon of
      dissociation is one essential characteristic of this disorder. The dissociation
      of the mental processes is demonstrated for the various basic functions. It
      implies a dissociation of contents and of parts of personality on the axis
      conscious-preconscious/unconscious. The dissociation ultimately becomes a
      prerequisite for living these not permitted and not integrated parts of
      personality in a partial and compromising way.

PMID- 8145873
TI  - [The Berlin follow-up study of eating disorders in adolescence. Part 2:
      Intermediate-term catamnesis after 4 years].
AB  - After more than four years, ten patients in a cohort of 60 consecutively-assessed
      adolescent patients with eating disorders were no longer available for follow-up-
      four had died and six refused to participate further. The follow-up interviews
      indicated varying rates of impairment in relation to eating disorders, menstrual
      anomalies, sexuality and psychosocial functioning. The distribution of continuing
      disorders at follow-up was a) 10% anorexia nervosa, b) 4% anorexia nervosa with
      bulimia, c) 18% anorectic and bulimic partial syndromes. The remaining 68% were
      found to have recovered. During the course of illness, there were few instances
      of anorectic symptoms crossing over into bulimic ones. A uniform pattern in the
      disease course was observed throughout the various self-evaluation
      questionnaires: reduction of symptoms that occurred during the course of the
      inpatient treatment could also be observed at the time of the follow-up. As
      compared with the international literature on follow-up studies, these can be
      considered as favorable findings.

PMID- 8145872
TI  - [Current status of interpersonal psychotherapy].
AB  - An overview of the state of the art in Interpersonal Psychotherapy (IPT) of
      depression is given. Since IPT is a standardized, efficient, and economical
      therapy form, it is anticipated that IPT will gain increasing importance in
      Germany in the field of psychiatry/psychotherapy. It can be learned by
      experienced psychotherapists, regardless of their psychotherapeutic orientation,
      in a standardized training program in a relatively short time. IPT is a short
      term psychotherapy designed specifically for the treatment of depression which
      was developed by Klerman and Weissman at the end of the sixties. It is based on
      the observation that depressive disorders usually occur in a psychosocial and
      interpersonal context. The focus of this psychotherapeutic procedure is therefore
      on dealing with the patients' psychosocial and interpersonal conflicts. The
      present article describes the use of IPT as well as its theoretical and empirical
      background. In addition the educational program in IPT is described and a
      comparison with other psychotherapies is given. Finally the article summarizes
      efficacy studies and derivative forms of IPT.

PMID- 8145874
TI  - [The Berlin follow-up study of eating disorders in adolescence. Part 3:
      Evaluation and prognosis].
AB  - This third report from the Berlin follow-up study of eating disorders in
      adolescence reports findings pertaining to evaluation and prognosis. Based on a
      systematic analysis of the relevant literature on the course of eating disorders,
      the following items were analyzed with respect to their value in predicting the
      psychopathological status of the patient at discharge from inpatient treatment
      and at follow-up: BMI at admission, age at onset of the disease, duration of
      symptoms before admission, personality features such as depression and
      neuroticism, the number of physical complaints, diagnosis (anorexia vs. bulimia),
      type of eating disorder (purger vs. restrictor), premorbid eating disorders or
      behavioral abnormalities, socioeconomic status, duration of in-patient treatment,
      and out-patient psychotherapy following discharge from the hospital. None of the
      factors predicted psychopathological status at either discharge or long-term
      follow-up.

PMID- 8145875
TI  - [Effect of assassination attempts on Lafontaine and Schauble on public opinion
      about psychiatric patients. Part 1: 1990 development].
AB  - In 1990 two assassination attempts against prominent German politicians were
      carried out by mentally ill persons. In the same year we conducted three
      representative surveys of the adult population of the FRG (old Lander and West
      Berlin) which allowed us to investigate the impact of both events on the attitude
      of the public towards the mentally ill. Already shortly after the first violent
      attack there was a marked increase of social distance, i.e. those questioned were
      less willing to have contact with a schizophrenic man. After the second
      assassination attempt the tendency to reject such a person increased again
      significantly. This applied to all forms of relationships studied. The increase
      of social distance is explained by the re-activation of the stereotype of the
      dangerous and unpredictable "insane" person.

PMID- 8145876
TI  - [Effects on assassination attempts on Lafontaine and Schauble on public opinion
      about psychiatric patients. Part 2: 1991 development].
AB  - As reported in the first part of our paper, in reaction to two assassination
      attempts carried out on schizophrenic persons there was a marked increase of
      social distance of the German public towards schizophrenic persons. Based on two
      further inquiries we are able to show that social distance decreased slightly
      during the course of 1991, but at the end of the year was still increased as
      compared with the situation in early 1990 before the first assassination attempt
      occurred. There was a corresponding trend in the popular stereotype of
      psychiatric patients. Our findings indicate, however, that the increase of social
      distance was specific for schizophrenic behaviour, since no such development
      could be observed in relation to major depressive disorder, for which the degree
      of rejection by the public did not change during the study period. Comparison
      between the first and final surveys reveals that, besides those persons who had
      never had contact with psychiatric patients, those who were personally involved
      as patients or relatives also reacted to the acts of violence by an increase in
      social distance. Among those who themselves were providing professional or lay
      help, or who had psychiatric patients among their friends or acquaintances, in
      contrast, the degree of social distance remained unchanged.

PMID- 8145877
TI  - ["Mediumistic psychoses". A case report].
AB  - Psychiatric diseases resulting from occult practices or spiritualist influences
      have long been known Henneberg in 1919 first described independent forms
      concelved as having a psychological genesis as "mediumistic psychoses". The
      continued importance of these disorders and the difficulties in their typological
      classification are illustrated by reference to a patient of our own who had
      pronounced auditory hallucinations. In classifying "mediumistic psychoses", it
      appears appropriate to give first consideration to atypical schizophrenic
      disorder.

PMID- 8145878
TI  - [Severe "late" dystonia after neuroleptic anxiolysis with fluspirilene].
AB  - The development of severe tardive dystonia after short-term use of low-dose
      Fluspirilen is described. A 39-year-old woman was treated with Fluspirilen IM by
      her family doctor for reactive depression. She did received no other neuroleptic
      agents and no risk factors for the development of tardive dyskinesia (e.g. old
      age or organic brain damage) were present. For the first time a relation between
      short-term monotherapy with Fluspirilen and tardive dyskinesia appears highly
      probable. The use of Fluspirilen for the treatment of psychogenic disturbances
      should therefore be considered carefully.

PMID- 8145879
TI  - [Diagnosis, epidemiology and therapy of seasonal depression].

PMID- 8145880
TI  - [Adult form of metachromatic leukodystrophy with predominantly psychotic
      manifestations].

PMID- 8145881
TI  - [Macromolecular inhibitors of crystallization in saliva and bile].
AB  - The current knowledges concerning macromolecular inhibitors of crystallization in
      saliva and in bile are reviewed. In saliva, four families of inhibiting proteins
      have been evidenced: the statherins, the acidic proline-rich proteins, the
      cystatins and the histatins. These proteins inhibit the nucleation and the growth
      of calcium phosphate salts. In the bile, two families of proteins that inhibit
      the nucleation of calcium carbonate and cholesterol are present: the
      apolipoproteins and the calcium binding protein also called anionic polypeptide
      fraction. The structure-function relationships of these molecules are
      particularly stressed.

PMID- 8145882
TI  - [Pancreatic lithostathine inhibitor of calcium carbonate precipitation: structure
      function relationship].
AB  - Pancreatic juice is naturally supersatured in calcium and bicarbonate ions. A
      mechanism controlling CaCO3 crystal formation and growth is therefore necessary
      to prevent duct clogging. Lithostathine, a glycoprotein synthesized by acinar
      cells and secreted in pancreatic juice, could be involved in such a control.
      Lithostathine significantly delayed crystal nucleation and inhibited growth of
      CaCO3 crystals from supersatured solutions. Lithostathine adsorbed to sites
      specifically inhibiting crystal growth with a dissociation constant Kd = 0.9 x
      10(-6) mol/L. The glycosylated N-terminal undecapeptide generated by limited
      trypsin hydrolysis of lithostathine, inhibited CaCO3 crystal growth with a Kd =
      3.4 x 10(-6) mol/L similar to that of lithostathine. On the contrary, the carboxy
      terminal polypeptide (lithostathine H) was inactive. The N-terminal undecapeptide
      of lithostathine is therefore essential to the inhibitory activity of the protein
      on CaCO3 crystal growth.

PMID- 8145883
TI  - [Renal lithostathine: a new protein inhibitor of lithogenesis].
AB  - Lithostathine is a protein of pancreatic secretion inhibiting calcium carbonate
      crystal growth. Antibodies to lithostathine were used to identify a related
      protein in urine and kidney stones. Western blot analysis of proteins extracted
      from concentrated normal urine or kidney stones demonstrated the presence of a
      protein with an apparent molecular weight of 23 kDa. The same antibodies were
      used in immunolocalization experiments on fresh human nephrectomy specimens
      cryosections. A positive signal was observed in the cells of proximal tubules and
      thick ascending limbs of Henle's loop. Protein extracts of renal stones inhibited
      calcium carbonate crystal growth. Because of its structural and functional
      similarities with pancreatic lithostathine, it was called renal lithostathine.

PMID- 8145884
TI  - [Crystallization of calcium phosphate in the presence of magnesium].
AB  - Formation and evolution of calcium phosphates are investigated, at 37 degrees C,
      in urine and aqueous solutions whose concentrations in calcium and magnesium are
      close to those of urine. Although the solutions are supersaturated with respect
      to all calcium phosphates, only an amorphous phase (ACP) and brushite (B)
      precipitate at time zero. Later on, ACP transforms either into whitlockite (W) or
      into apatite (HAP) depending on the solution composition. Phase transformations
      are discussed in terms of supersaturation, parameter which includes
      concentrations and pH. It is also shown that magnesium is a powerful inhibitor of
      the evolution towards HAP.

PMID- 8145885
TI  - [Model of calcium oxalate lithogenesis by kinetic turbidimetry].
AB  - The crystallization process of calcium oxalates in synthetic urine at 37 degrees
      C is followed by turbidimetry. As the solution absorbance is very sensitive to
      the number of particles in suspension, it is possible to distinguish nucleation
      and growth from agglomeration. In the former case, the slopes of the
      turbidimetric curves are positive whereas in the latter case, they are negative.
      Poisoning the solutions by some active additives induces changes of the slopes so
      that it becomes possible to know whether the additive is a promotor or an
      inhibitor of nucleation, growth or agglomeration. As an example, the model is
      tested for checking the influence of human urine on the crystallization process.
      It is shown that urine fractions of non stone-formers inhibit agglomeration when
      they contain macromolecules of high molecular weight (> 30,000 Da).

PMID- 8145886
TI  - [Exaggerated calciuric response to an acute acid load in patients forming renal
      calcium stones].
AB  - Calciuric response to an acute acid load was studied in 13 recurrent calcium
      stone formers and in 9 control subjects. The evolution of calcium and citrate
      urinary excretion related to creatinine, of plasma acid base status, of urinary
      pH, of acid excretion was analysed before and after NH4Cl administration (2
      mmol/Kg). Fasting calciuria (expressed as Ca/Cr) was identical in the 2 groups,
      however the urinary calcium excretion after the acid load was greater in the
      stone formers group than in the controls (0.378 +/- 0.113 vs 0.253 +/- 0.108
      mg/mg). The increase in acid excretion and the decrease in urinary citrate
      excretion were identical in the 2 groups.

PMID- 8145887
TI  - [Correlation between protein and sodium intake and calciuria in calcium
      lithiasis].
AB  - In order to assess the influence of dietary protein and salt intake on urinary
      calcium excretion in calcium stone formers, we simultaneously determined 24 hour
      urinary excretion of Urea (UU) and sodium (UNa) together with that of calcium
      (UCa) in 184 patients (112 males) with idiopathic calcium nephrolithiasis studied
      on free diet. Mean (+/- SEM) values expressed as mmol/kg BW/day of both UU and
      UNa were higher in hypercalciuric (UCa > or = 0.1 mmol/kg/d, mean 0.15 +/- 0.01)
      male patients, respectively 6.63 +/- 0.25 and 2.71 +/- 0.13, than in
      normocalciuric males, respectively 5.33 +/- 0.22 (p < 0.001) and 2.36 +/- 0.15 (p
      = 0.06), while the latter did not differ from healthy controls. Similar findings
      were made in female stone formers. Linear regression analysis on the whole series
      showed a positive but weak correlation between UU and UCa (r = 0.47, p < 0.001)
      and between UNa and UC a (r = 0.33, p < 0.001), but the slope of the relation
      UCa/UU was increased only in hypercalciurics, whereas it did not differ between
      normocalciurics and controls. By multiple regression analysis, variations of UU
      and UNa altogether accounted only for 22% of variation in UCa. We conclude that
      in both sexes hypercalciuric stone formers have a higher protein and sodium
      intake than normocalciurics, and for a given urinary urea output, their mean
      urinary calcium excretion is higher, thus suggesting that hypercalciuric stone
      formers are electively sensitive to the hypercalciuric effect of high protein
      intake.

PMID- 8145889
TI  - [Genetic and environmental factors implicated in recurrent calcium lithiasis].
AB  - In this prospective study, we compared the frequency of some genetic and
      environmental factors possibly implicated in the occurrence of calcium stone
      disease. A group of 439 patients (258 males and 181 females) with one episode of
      calcium stone was compared to a group of 191 patients (131 males and 60 females)
      with recurrent calcium stone disease. Population with stones was also compared to
      control population (n = 78, 40 males and 38 females) matched to age. Major
      results were as follow: 1) Family history of urinary calculi was more frequent in
      patients than in controls (28.4% vs 9%, p < 0.01). No difference was observed
      between patients with one episode and those with recurrent episodes (27% vs 31%,
      ns). 2) The recurrence was earlier in female than in male, so that in female with
      family history of urinary calculi (p < 0.05). 3) Mean plasma levels of 1-25OH2D3
      was significantly higher in patients with family history than in controls (60% vs
      38%, p < 0.01) 5) Restricted calcium diet (< 400 mg per day) was more often
      observed in patients than in controls (31% vs 14%, p < 0.05) and the most
      significant difference was found in patients with recurrent calcium stones.

PMID- 8145888
TI  - [Results of dietary evaluation during calcium oxalate and calcium phosphate
      lithiasis].
AB  - In order to better understand the role of diet in etiology of urolithiasis, 84
      oxalo-phospho-calcic-lithiasic patients (52 men, 32 women) have been studied by a
      nutritional week-interview and by urinary and blood testing. Diet data were
      compared to an ideal standard. Total caloric intake was 2428 +/- 651 calories/d;
      this intake is high in 7% women and 40% men. 79% out of patients are fat.
      Protidic intake is 87 +/- 21 g/d higher than 1 g/kg/d in 84.5% of patients.
      Lipids are high in 38.9 +/- 7%, glucid are low in 45.3 +/- 7%. Calcium intake is
      934 +/- 406 mg/d, sodium intake is 12.9 + 3 g/d. Water intake is 2305 +/- 759
      ml/d. Different groups of patients are studied: a) 21 patients with mean age of
      43 +/- 12 years have recurrent lithiasis (R). This group is compared to 48
      patients with 37 +/- 44 years who have a single lithiasis. Half of (R) patients
      have hypercalciuria, hyperphosphaturia and hyperoxaluria. Diet study is no
      different between these two groups. b) Other groups are studied: 21 have
      hyperophosphaturia (HPU) without hypophosphoremia and they have hypercalciuria,
      hyperuraturia and high urinary urea; diet shows higher glucicid and potassium
      intake than group with normal phosphaturia; 23 have hypercalciuria (HCU) and high
      uraturia and phosphaturia: diet study shows no difference with a group with
      normal calciuria. 21 have hyperoxaluria (HOU): diet study of a normal oxaluric
      group shows higher lipid intake, lower glucidic and calcium intake; 22 have
      hyperuraturia (HAU) and higher urinary urea, sodium and potassium than
      normouraturia group: in this group potassium intake is higher.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8145890
TI  - [Short and long term complications of lithotripsy on renal function].
AB  - Today, most stones can be removed by minimally invasive means. Extracorporeal
      Shock Wave Lithotripsy (ESWL) is the preferred form of treatment for symptomatic
      upper ureteral and renal calculi less than 2 cm a diameter. The short and long
      term complications of ESWL are underestimated. Thus, ESWL may cause renal trauma
      and such trauma may induce later hypertension. In this retrospective study, we
      reviewed the frequency of deleterious effects of ESWL in 45 patients who had
      undergone ESWL from January 1988 to September 1989. Short-term complications were
      macroscopic hematuria (15%), lumbar pain (11%) and peri- or intrarenal hematomas
      (4.4%). Two years later CT scan was performed in 20 patients. It was normal in 7
      (35%). In others, it shown a recurrence of stone in 8 (40%) and a focal scarring
      in 5 (25%). Only 1 out of 43 patients had developed hypertension.

PMID- 8145891
TI  - Voltage-dependent potassium currents in ovine somatotrophs and their function in
      growth hormone secretion.
AB  - Sheep somatotroph-enriched cultures were obtained by means of enzyme dissociation
      and Percoll gradient separation. Nystatin-perforated-whole-cell recordings were
      performed on post-recording-identified somatotrophs after 4-14 days in vitro.
      Using Ca(2+)-free, tetrodotoxin-containing (1 microM) bath solution and K+
      electrode solution, three types of voltage-dependent K+ currents were recorded as
      inward rectifying, outward transient and outward delayed rectifying K+ currents.
      The inward rectifying K+ current was very small at physiological extracellular K+
      concentrations (5 mM) and enhanced by increasing the K+ concentration in the bath
      to 55 mM; it was blocked by tetraethylammonium (2 mM) but not by 4-aminopyridine
      (5 mM). A transient outward K+ current appeared at -50 mV and was selectively
      diminished by 4-aminopyridine (2 or 4 mM). A delayed rectifying outward K+
      current was observed when the membrane potential was depolarized to -20 mV and
      was blocked by tetraethylammonium (2 mM) but not 4-aminopyridine (4 mM).
      Application of 4-aminopyridine but not tetraethylammonium (up to 5 mM)
      depolarized the cell membrane potential recorded under current clamp conditions
      and triggered action potentials when the bath solution contained Ca2+ (2 mM) but
      not tetrodotoxin. The intracellular Ca2+ concentration was increased by 4
      aminopyridine as was growth hormone release. Therefore, the 4-aminopyridine
      sensitive transient outward K+ current appears to be important in the determining
      the resting potential of ovine somatotrophs and plays a major role in regulating
      basal intracellular Ca2+ concentration and growth hormone secretion.

PMID- 8145892
TI  - Epidermal growth factor treatment induces D2 dopamine receptors functionally
      coupled to delayed outward potassium current (IK) in GH4C1 clonal anterior
      pituitary cells.
AB  - GH4C1 cells, a clonal cell line from a rat pituitary tumor, have been widely used
      as a model to study the regulation of prolactin secretion. These cells, however,
      do not express dopamine D2 receptors and are therefore not suitable for exploring
      mechanisms involved in dopamine inhibition of prolactin secretion. The recent
      demonstration that epidermal growth factor (EGF) is able to induce functional
      expression of D2 receptors in GH3 cells, a parental clonal cell line, overcomes
      this difficulty. We have thus undertaken an electrophysiological study in order
      to check whether coupling of D2 receptors to K+ channels could be restored in
      that model. Effects of dopamine on the non-inactivating voltage-dependent outward
      K+ current (IK) were investigated both in control and in EGF-treated GH4C1 cells.
      The K+ current was not modified by EGF treatment alone. In control cells, IK
      measured before and during dopamine application was unchanged. In contrast,
      dopamine application markedly enhanced the K+ current in cells that had
      previously been exposed to EGF. The effect was mimicked by the specific D2
      receptor agonist bromocriptine and blocked by sulpiride, a D2 receptor
      antagonist, thus indicating that the effect of dopamine was effectively due to
      the activation of D2 receptors. These results bring further evidence that EGF
      induced D2 receptors in clonal strains from rat pituitary tumors are functional
      and are coupled to the delayed outward K+ current IK.

PMID- 8145893
TI  - Attenuation of clonidine-induced growth hormone release following chronic
      glucocorticoid and 5-hydroxytryptamine uptake-inhibiting antidepressant
      treatments.
AB  - Administration of various doses of clonidine increased plasma growth hormone
      levels in male Wistar rats. Chronic hydrocortisone treatment produced significant
      decreases in ACTH levels as well as a significant attenuation of clonidine
      induced increases in growth hormone levels. Similarly, chronic treatment with 5
      HT uptake-inhibiting antidepressants such as fluoxetine, clomipramine and
      imipramine also significantly attenuated clonidine-induced increases in growth
      hormone levels. On the other hand, chronic treatment with clorgyline (monoamine
      oxidase type A-inhibiting antidepressant) and 5-HT agonists, such as m
      chlorophenylpiperazine, 1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane and 8
      hydroxy-2-(di-n-propylamino)tetralin, did not have any significant effect on
      clonidine-induced increases in growth hormone levels. These findings suggest that
      development of functional subsensitivity of either alpha 2-adrenergic
      heteroreceptors or 5-HT1C receptors mediating clonidine-induced growth hormone
      secretion following chronic treatment with glucocorticoids and 5-HT uptake
      inhibitors.

PMID- 8145894
TI  - Ontogeny of angiotensin-II-induced prolactin release in vivo and in vitro in
      female and male rats.
AB  - The prolactin-releasing effect of angiotensin II (AII) was studied in the
      developing female and male rat in vivo and in vitro. AII (50 and 100
      micrograms/100 g b.w.) was injected intraperitoneally to female and male rats
      aged 4, 12, 20 and 28 days and males aged 38 days. AII (10(-6) M) was also tested
      in pituitaries incubated in vitro from animals of both sexes aged 12, 20 and 28
      days. In addition, as two subtypes of AII receptors have been characterized on
      the basis of displacement with specific AII antagonists, we used the nonpeptide
      AII receptor antagonists losartan (AT1 subtype) and PD 123319 (AT2 subtype) to
      determine the AII receptor subtype functionally involved in AII-induced prolactin
      secretion in vivo in 25-day-old male rats. The efficiency of the prolactin
      releasing effect of AII in vivo increased with age, and first responses were
      observed at 20 days of age in both sexes. No sexual differences were encountered.
      On the other hand, AII-induced prolactin release from pituitaries incubated in
      vitro was first demonstrated at 12 days in females and at 20 days in males. The
      effect increased with age in both sexes, and, at 28 days, pituitaries from
      females released more prolactin in response to AII than those from males.
      Losartan (3 mg/kg) completely abolished AII (50 micrograms/100 g b.w.)-induced
      prolactin release in vivo, while PD 123319 (3 mg/kg) did not. This suggests that
      pituitary AT1 receptors are functionally involved in the prolactin release
      induced by AII in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8145895
TI  - Analysis of pituitary prolactin and adrenocortical response to ether, formalin or
      restraint in lactating rats: rise in corticosterone, but no increase in plasma
      prolactin levels after exposure to stress.
AB  - It is well established that stress causes a rise in plasma prolactin (PRL) levels
      of male or cycling female rats. In lactating animals, the pituitary PRL response
      to stress is not well understood. Therefore, the purpose of the present study was
      to analyze this question in lactating rats having low or elevated prestress
      plasma PRL levels. The animals were exposed to ether, formalin or restraint, and
      plasma PRL and corticosterone levels were determined. In mothers continually
      together with their pups, plasma PRL levels decreased significantly after
      exposure to ether vapor or injection of formalin under the skin. At the same
      time, both agents caused a significant rise in blood corticosterone
      concentrations. Lactating rats isolated for 4 h had very low levels of PRL before
      application of stress. However, neither formalin nor restraint caused any
      elevation in their plasma PRL levels although both interventions increased blood
      corticosterone concentrations. Lactating mothers receiving formalin after a 30
      min suckling stimulus preceded by 4 h isolation did not show appreciable changes
      in pituitary PRL secretion following the administration of formalin. For
      information on the mechanism of the effect of stress on PRL, lactating rats were
      pretreated with the dopamine receptor antagonist domperidone (injecting 80
      micrograms/kg body weight) or were adrenalectomized 7 days prior to exposure to
      stress. The very high levels of PRL caused by domperidone decreased markedly in
      animals subjected to restraint stress. Administration of formalin to
      adrenalectomized lactating rats continually together with their litter caused a
      slight immediate decrease, followed by a transitory elevation and a subsequent
      small second decrease in blood PRL concentration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8145896
TI  - Reduced availability of milk after central injections of corticotropin-releasing
      hormone in lactating rats.
AB  - Corticotropin-releasing hormone (CRH) plays a major role in activating the
      pituitary-adrenal axis in stress; its central application may therefore be
      expected to mimic stress. Since stress reportedly disrupts lactation, experiments
      were designed to study the effects of CRH administration upon the transfer of
      milk from rat mothers to their pups and to examine some of the possible
      underlying physiological mechanisms. CRH was administered
      intracerebroventricularly to primiparous rats on the 8th day of lactation
      immediately prior to being reunited with 8 of their overnight-separated pups.
      Changes in litter weights were measured for a period of up to 4 h as an index of
      milk procurement by the young (milk transfer); a qualitative assessment of
      maternal behaviour was also made. Treatment of dams with 0.1-1 nmol CRH resulted
      in a dose-dependent reduction in the amount of milk obtained by the pups.
      Conscious mothers treated with CRH initially showed intense behavioural
      activation; these events (mainly hyperlocomotion and grooming) in the mother
      resulted in reduced opportunities for nipple attachment by the pups and, thus,
      milk transfer. On the other hand, milk transfer was also significantly reduced in
      urethane-anaesthetized mothers treated with CRH, indicating that behavioural
      activation cannot have been the sole factor underlying the CRH-induced inhibition
      of milk transfer in awake dams. Although oxytocin (OT) release is stimulated by a
      variety of stressors, the possibility of an inhibitory effect of CRH upon OT
      secretion and/or disruption of the reflex arc serving milk ejection was
      considered. The peripheral administration of OT (100 mU/rat s.c.) did not,
      however, surmount the inhibitory actions of CRH upon milk transfer.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8145897
TI  - Prolactin receptor immunoreactivity in rat anterior pituitary.
AB  - Prolactin (PRL) receptors have been identified in both classical and nonclassical
      target organs. Actions of PRL on the secretion of anterior pituitary hormones
      have been reported. In order to confirm the presence of PRL receptors on specific
      cell types of the anterior pituitary, immunocytology on ultrathin frozen sections
      was carried out using monoclonal antibodies specific to the rat PRL receptor.
      Anterior pituitary glands were removed and fixed in 4% paraformaldehyde or 2.5%
      glutaraldehyde and postfixed in 1% osmium tetroxide. Tissues were frozen and
      ultrathin sections were made by cryoultramicrotomy. In anterior pituitary cells,
      all endocrine cell populations showed PRL-R-like immunoreactivity. The relative
      labeling frequency based on immunolabeling studies was somatotrophs > lactotrophs
      > thyrotrophs approximately corticotrophs > gonadotrophs. Within all endocrine
      cell types, no apparent differences could be observed in the subcellular
      localization of PRL-R-like immunoreactivity. At the subcellular level, gold
      particles, either isolated or in groups of two, were seen at the level of the
      plasma membrane, in the cytoplasmic matrix, in the vicinity of the endoplasmic
      reticulum and in the nucleus. The identification of receptors specific to PRL
      within different cells of the anterior pituitary raises the interesting
      possibility that PRL may act via an autocrine or paracrine network in regulating
      anterior pituitary function.

PMID- 8145898
TI  - Adenohypophyseal vasoactive intestinal peptide and neuropeptide Y responses to
      hypothyroidism are abolished after anterolateral deafferentation of the
      hypothalamus.
AB  - We examined whether hypothyroidism-induced increases in the anterior pituitary
      content of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) are
      mediated by the hypothalamus. Male Sprague-Dawley rats were anesthetized and one
      of the following surgeries was performed: (1) sham thyroidectomy, (2)
      thyroidectomy, (3) thyroidectomy plus surgical anterolateral deafferentation of
      the medial basal hypothalamus, or (4) thyroidectomy and sham deafferentation of
      the hypothalamus (knife was inserted but not rotated). Two weeks after surgery,
      animals were killed and tissue samples collected for measurement of the anterior
      pituitary VIP and NPY and plasma thyroid-stimulating hormone (TSH), thyroxine,
      and prolactin concentrations (by RIA). Reverse-phase HPLC showed that VIP and NPY
      immunoreactivities in the anterior pituitary extracts are eluted in the positions
      identical to synthetic VIP and NPY, respectively. Only data from those animals
      with complete symmetric cuts located at the posterior border of the optic chiasm
      were included for analysis. In the thyroidectomized rats the anterior pituitary
      contents of VIP and NPY were significantly increased. These responses were almost
      completely prevented by the anterolateral deafferentation of the hypothalamus.
      Sham hypothalamic deafferentation had no effect on the pituitary neuropeptide
      responses to hypothyroidism. Anterolateral deafferentation of the hypothalamus
      also significantly blunted plasma TSH responses to hypothyroidism. These data
      suggest that some hypothalamic factor is involved in the mediation of the effect
      of hypothyroidism on the pituitary content of VIP and NPY.

PMID- 8145899
TI  - Inhibition of rat pituitary tumor cell proliferation by benzodiazepines in vitro.
AB  - The effect of various benzodiazepines (peripheral-type receptor ligands: Ro 5
      4864, PK 11135; central-type receptor ligands: clonazepam, Ro 15-1788, Ro 15
      4513; mixed type: diazepam) on the proliferation of estrogen-induced rat
      pituitary prolactin-secreting tumor cells was studied in vitro. [3H]thymidine
      incorporation into DNA was used as an index of cell proliferation. It was found
      that tested peripheral- and mixed-type benzodiazepine receptor ligands
      significantly suppressed the pituitary cell proliferation in a dose-dependent
      manner (10(-4)-10(-8) M). The inhibitory effect of Ro 5-4864 was reversed by 5 x
      10(-3) M calcium chloride. On the other hand, central-type benzodiazepine
      receptor ligands suppressed tumor cell proliferation only at the highest
      concentration studied (10(-4) M). Our results indicate that benzodiazepines might
      exert an antiproliferative action on pituitary tumor cell growth, and that this
      effect seems to be a calcium-dependent process.

PMID- 8145900
TI  - Circadian sneezing.
AB  - Prompted by the observation that a fellow medical student sneezed at about the
      same time in class every morning, we recorded the time of each of the 118 sneezes
      she made on 69 days over a 6.5-month period. Analysis of the sneeze times with
      the goodness-of-fit test revealed a highly nonuniform distribution (p < 0.0001)
      with a significantly increased probability of sneeze production within a small
      time interval centered at 8:20 AM. After ruling out the known causes of sneezing,
      we propose that the subject had a circadian fluctuation in her sneeze threshold
      independent of any immediate external stimulus. We compare this circadian rhythm
      to other periodic phenomena such as cyclic esotropia and rapid-cycling bipolar
      disease as well as to illnesses such as the periodic paralyses in which rapid and
      reversible changes occur in the neuromuscular system, and we discuss the peculiar
      circumstances favorable to documenting a circadian sneeze.

PMID- 8145901
TI  - Physical therapy and Parkinson's disease: a controlled clinical trial.
AB  - In a randomized, single-blind, crossover study, we evaluated physical disability
      in moderately advanced Parkinson's disease (PD) patients after 4 weeks of normal
      physical activity and 4 weeks of an intensive physical rehabilitation program. We
      used a timed motor task and a standard assessment of PD severity (the Unified
      Parkinson's Disease Rating Scale [UPDRS] with subscales for mentation, activities
      of daily living [ADL], and motor function) completed by an investigator blinded
      to the physical rehabilitation status of the patient. Following physical
      rehabilitation, there was significant improvement in the UPDRS ADL and motor
      scores, but no change in mentation score. During the 6 months following physical
      rehabilitation, patients did not regularly exercise, and the UPDRS scores
      returned to baseline. We conclude that physical disability in moderately advanced
      PD objectively improves with a regular physical rehabilitation program, but this
      improvement is not sustained when normal activity is resumed.

PMID- 8145902
TI  - The epileptic spectrum in the congenital bilateral perisylvian syndrome. CBPS
      Multicenter Collaborative Study.
AB  - We studied the frequency, clinical and EEG characteristics, and outcome of the
      epileptic syndrome in 31 patients with a congenital neurologic syndrome
      characterized by pseudobulbar palsy, cognitive deficits, and bilateral
      perisylvian polymicrogyria. Seizures were present in 27 of 31 patients (87%) and
      usually began between the ages of 4 and 12 years; they commonly consisted of
      atypical absence, atonic/tonic, and generalized tonic-clonic seizures. Partial
      attacks were present in 26%. EEG demonstrated generalized spike and wave
      abnormalities and, less frequently, multifocal discharges, predominantly in
      centro-parietal regions. Seizures were poorly controlled in 65%, with the
      remaining patients well controlled. Seven patients underwent callosotomy, which
      resulted in seizure improvement. This study indicates that the epileptic spectrum
      in this syndrome is broad but follows predictable patterns. Callosotomy is a
      valuable treatment strategy in those with intractable drop attacks.

PMID- 8145903
TI  - Large cerebral vessel occlusive disease in systemic lupus erythematosus.
AB  - We systematically investigated clinical, laboratory, radiologic, and pathologic
      features, including treatment and prognosis, of stroke syndromes in 30 patients,
      six from our institution and 24 from the literature, with systemic lupus
      erythematosus (SLE) and symptomatic large cerebral vessel occlusive disease,
      documented by angiography or autopsy. The average age at stroke onset was 35
      years, and the diagnosis of SLE was made on average 4.4 years prior to that. At
      least 86% had active SLE at the time of their stroke. Headache was common at
      onset. We found major intracranial or extracranial vessel occlusive process by
      (1) thrombus, (2) dissection, (3) fibromuscular dysplasia or vasculitis, and (4)
      atherosclerosis. The presumed mechanisms were coagulopathy, cardiogenic embolism,
      large cerebral vessel vasculitis or occlusive vasculopathy, cervical arterial
      dissection, and premature atherosclerosis. The short-term death rate was 40% and
      the recurrent stroke rate was 13%. We conclude that symptomatic large cerebral
      vessel occlusive disease in SLE generally occurs several years after the
      diagnosis of SLE, usually during the active phase of the disease, is related to
      heterogeneous mechanisms, and carries a relatively poor short-term outcome.

PMID- 8145904
TI  - Utility and reliability of placebo infusion in the evaluation of patients with
      seizures.
AB  - Placebo infusions are occasionally used to elicit psychogenic seizures. How
      frequently placebo infusions elicit patients' typical events, atypical and
      potentially confusing events, or even epileptic seizures is not known. We report
      the results of placebo infusions during video EEG in 68 patients who also had
      events recorded without placebo. A single investigator administered a saline
      placebo that was represented to the patient as an activating substance. We
      compared the events recorded without placebo with events recorded with placebo.
      Twenty patients had only epileptic seizures without placebo; with placebo, two of
      20 (10%) had their typical epileptic seizures and three of 20 (15%) had atypical
      nonepileptic events. Forty patients had only psychogenic seizures without
      placebo; with placebo, 33 of 40 (82%) had their typical psychogenic seizures and
      three of 40 (8%) had atypical events. Eight patients had both psychogenic and
      epileptic seizures without placebo; with placebo, four of eight had their typical
      psychogenic seizures. Thus, placebo infusion elicits typical psychogenic events
      in most patients with psychogenic seizures, but atypical events or epileptic
      seizures may occur in a minority and lead to incorrect diagnosis.

PMID- 8145905
TI  - Familial Sneddon's syndrome: clinical, hematologic, and radiographic findings in
      two brothers.
AB  - We present the clinical, hematologic, and radiographic findings in two brothers
      with Sneddon's syndrome (stroke and livedo reticularis) and antiphospholipid
      antibodies. Patient 1 had anticardiolipin antibody and patient 2 had lupus
      anticoagulant, which we detected only upon repeated blood testing. One should
      test for both anticardiolipin antibody and lupus anticoagulant and repeat the
      screenings before determining a Sneddon's syndrome patient's antiphospholipid
      antibody status. Both Sneddon's syndrome and the primary antiphospholipid
      antibody syndrome are potentially familial causes of stroke. In familial cases,
      an inherited predisposition to antiphospholipid antibody production may be
      involved in disease pathogenesis.

PMID- 8145906
TI  - Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation
      rate, MRI signs of disease activity, and lymphocyte interferon gamma production
      in relapsing-remitting multiple sclerosis.
AB  - We report a randomized, double-blind, placebo-controlled pilot trial of systemic
      high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing
      remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n =
      12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical
      exacerbations or new or enlarging lesions on serial MRI occurred in two of 12
      rIFNA-treated and in seven of eight placebo-treated patients (p < 0.005). There
      was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging
      lesions were present in the placebo group (p < 0.01). Baseline lymphocyte
      interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to
      3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, whereas production was
      unchanged in the placebo group. The rIFNA was tolerated without dropouts or
      serious side effects, but fever, malaise, fatigue (interfering with daily
      activities in two patients), and leukopenia occurred frequently.
      Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might
      reduce clinical and MRI signs of disease activity in RR MS and should be
      investigated in larger trials.

PMID- 8145907
TI  - Phase 1 clinical trial of chimeric monoclonal anti-CD4 antibody in multiple
      sclerosis.
AB  - We conducted an open trial of cM-T412, a chimeric monoclonal anti-CD4 antibody,
      in 29 patients with MS. This antibody caused a prompt and long-lasting depletion
      of circulating CD4 (helper/inducer) lymphocytes. The mean (+/- SE) CD4 count for
      the group decreased from 870 (+/- 66) cells/mm3 at baseline to 76 (+/- 11) 3
      hours after treatment, and then increased to 425 (+/- 38) at 1 month after
      treatment and 475 (+/- 39) at 6 months after treatment. Numbers of CD8
      (cytotoxic/suppressor) lymphocytes, B lymphocytes, granulocytes, and monocytes
      changed transiently but showed no significant long-term effects. The most common
      side effects were headache, nausea, myalgia, fever, and tachycardia occurring in
      the first few hours after treatment. No serious or unexpected infections or other
      significant adverse effects occurred. Kurtzke EDSS scores remained stable, and
      MRI scans showed less contrast enhancement 1 week after treatment. We conclude
      that treatment of MS patients with cM-T412 chimeric anti-CD4 antibody is well
      tolerated at the doses tested and produces a long-lasting, selective depletion of
      CD4 lymphocytes.

PMID- 8145908
TI  - Relationship between frontal lobe lesions and Wisconsin Card Sorting Test
      performance in patients with multiple sclerosis.
AB  - Conceptual reasoning deficits are common in patients with multiple sclerosis (MS)
      and are typically associated with focal lesions involving the frontal lobes. In
      this study, we predicted that MS patients with frontal white matter lesions (MS
      F) would be more impaired on a standard conceptual reasoning task (Wisconsin Card
      Sorting Test; WCST) than patients with minimal frontal lesions (MS-NF), even if
      the total cerebral lesion area (TLA), measured from MRI, was equivalent across
      groups. We subdivided 43 definite MS patients into three groups based on MRI
      findings: seven in the MS-F group (mean TLA = 41.4 cm2) and seven in the MS-NF
      group (mean TLA = 50.0 cm2); 29 MS patients served as a low lesion burden control
      group (MS-C; mean TLA = 6.4 cm2). The groups did not differ with regard to
      demographic and illness characteristics. Although the three subgroups obtained
      comparable scores on a measure of global cognitive functioning (verbal
      intelligence), the MS-F group achieved significantly fewer categories and made
      more total errors on the WCST than did the MS-NF and MS-C groups. The MS-F group
      made significantly more perseverative responses than the MS-C group and
      nonsignificantly more than the MS-NF group. These results suggest that the
      pattern of cognitive decline in MS is a function of the location of demyelinating
      lesions within the cerebral hemispheric white matter. Finally, we supplement the
      group study results with a case report of an MS patient who was studied serially
      with MRI and cognitive testing.

PMID- 8145909
TI  - The prevalence of multiple sclerosis in the Sanitary District of Velez-Malaga,
      southern Spain.
AB  - Since little is known about the prevalence of multiple sclerosis (MS) in Spain,
      we undertook an epidemiologic study to ascertain the prevalence of MS in the
      Sanitary District of Velez-Malaga, close to the city of Malaga, in southern
      Spain. The crude prevalence rate of MS in Velez-Malaga was 53 per 100,000, twice
      as high as the prevalence previously reported in both the city and province of
      Malaga. The MS prevalence in the Sanitary District of Velez-Malaga is similar to
      that in Sicily and in Cyprus.

PMID- 8145910
TI  - Intravenous immunoglobulin treatment in patients with motor neuron syndromes
      associated with anti-GM1 antibodies: a double-blind, placebo-controlled study.
AB  - We studied the effects of intravenous immunoglobulin (IVIg) in 12 patients with
      motor neuron syndromes associated with high titers of anti-GM1 antibodies. Five
      of the patients had conduction blocks. The study design was a double-blind,
      placebo-controlled, crossover trial with IVIg (0.4 g/kg body weight per day
      injected for 5 consecutive days). We evaluated the patients before and 5, 28, and
      56 days after drug administration using a computerized analyzer for muscle
      strength, the Norris scale for disability, motor nerve conduction velocities for
      patients with conduction blocks, and measurements of immunologic markers.
      Compared with placebo, IVIg induced a significant increase in muscle strength
      only in the patients with conduction blocks.

PMID- 8145911
TI  - Incidence of cluster headaches: a population-based study in Olmsted County,
      Minnesota.
AB  - The epidemiology of cluster headache is virtually unknown. Using the unique
      resources of the Rochester Epidemiology Project for population-based studies, we
      identified 26 Olmsted County, Minnesota, residents who fulfilled the
      International Headache Society criteria for newly diagnosed cluster headache
      between 1979 and 1981. As part of a large study of migraine and cluster headache,
      we screened more than 6,400 patient records from several diagnostic rubrics to
      obtain this cohort, accomplished case ascertainment exclusively through medical
      record review, and assigned diagnoses by the consensus of two neurologists. The
      age-adjusted incidence was 15.6 per 100,000 person-years (p-y) (95% CI, 8.9 to
      22.3) for males and 4.0 per 100,000 p-y for females (95% CI, 0.4 to 7.6). The
      overall age- and sex-adjusted incidence was 9.8 per 100,000 p-y (95% CI, 6.0 to
      13.6) or approximately 1/25 that of migraine. The peak incidence was among men
      aged 40 to 49 years and women 60 to 69 years. There was a higher than expected
      prevalence of history of smoking among males with cluster headaches (p < 0.05),
      supporting the possibility that smoking predisposes to the development of cluster
      headaches in men.

PMID- 8145912
TI  - Familial juvenile parkinsonism: clinical and pathologic study in a family.
AB  - We describe a family with juvenile-onset parkinsonism, which improved following
      sleep. Four of the five siblings in this family developed a similar onset of
      parkinsonism at an early age, and the parents were first cousins. In one of the
      siblings, a 67-year-old woman, pathologic changes at autopsy were confined to the
      substantia nigra pars compacta (SNPC) and locus ceruleus. The SNPC revealed
      obvious neuronal loss and gliosis in the medial and ventrolateral regions. In the
      remainder of the SNPC and the locus ceruleus, the population of neurons was
      reduced and there was low melanin content in most of the neurons but no
      detectable gliosis or extraneuronal free melanin pigment suggestive of a
      neurodegenerative process. There were no Lewy bodies. The entire pathologic
      picture was different from that of Lewy body Parkinson's disease.

PMID- 8145913
TI  - Facioscapulohumeral muscular dystrophy (FSHD): design of natural history study
      and results of baseline testing. FSH-DY Group.
AB  - Faciscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder
      with a characteristic distribution of weakness and variable severity.
      Prospective, longitudinal data on FSHD are essential for the design of
      therapeutic trials and in assessment of genetic heterogeneity. We enrolled 32
      well-defined FSHD patients and 32 normal subjects in a natural history study of
      FSHD. All subjects underwent baseline quantitative muscle testing (QMT), manual
      muscle testing (MMT), and functional testing. QMT demonstrated substantial
      weakness in muscles usually spared in FSHD. Major right/left side-to-side
      differences in strength were documented but, unexpectedly, were not related to
      handedness. Using the QMT data on normal subjects, we developed regression models
      relating strength to age, gender, and height and used these models to standardize
      QMT measurements in FSHD patients, expressing them as the number of SDs from
      average normal performance. This model-based strategy should facilitate the
      construction of composite scores to describe the natural history of FSHD and
      could be useful for constructing sensitive measures of progression in other
      neuromuscular diseases.

PMID- 8145914
TI  - Dihydroergotamine nasal spray for the acute treatment of migraine.
AB  - We conducted a multicenter, double-blind, parallel-group study to compare the
      efficacy and safety of dihydroergotamine (DHE) nasal spray and placebo over 4
      hours in the treatment of migraine. Of the 112 patients enrolled, 100 were
      included in the "intent-to-treat" efficacy analysis. The patients self
      administered either 2.0 mg DHE (0.5 mg per nostril, repeated after 15 minutes) or
      placebo at the onset of two separate headaches and rated hourly the drugs'
      effects on pain severity, pain relief, nausea, and vomiting. The physicians
      assessed the overall effectiveness of the drugs in relieving headache pain,
      nausea, and vomiting. Both the patients' and physicians' ratings indicated that
      DHE was significantly superior to placebo in improving headache and nausea;
      according to the patients' ratings, these between-group differences were already
      significant at the first (hour 1) evaluation. There were no significant
      differential treatment effects with respect to relief of vomiting. Most adverse
      events were mild or moderate, confined to the nasopharyngeal area, and probably
      related to the route of administration. We conclude that DHE nasal spray is a
      safe and effective treatment for the pain and nausea of migraine attacks.

PMID- 8145915
TI  - The diagnostic value of SPECT with Tc 99m HMPAO in Alzheimer's disease: a
      population-based study.
AB  - We studied the diagnostic accuracy of single-photon emission computed tomography
      (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m
      HMPAO) in 48 patients with probable Alzheimer's disease (AD) according to NINCDS
      ADRDA criteria and in 60 controls recruited from a population-based study. With
      logistic regression, we identified decreased temporal regional cerebral blood
      flow as the best discriminating variable between patients and controls. Receiver
      operator characteristic curves showed that the discriminative ability of SPECT
      improved with increasing dementia severity. With specificity set at 90%,
      sensitivity figures were 42% in mild, 56% in moderate, and 79% in severe AD. The
      diagnostic gain as a function of the prior probability of the disease being
      present was computed for those with mild AD. When the prior probability varied at
      around 50%, the diagnostic gain for mild AD patients was substantial (a maximum
      of 34%) for a positive test result but poor for a negative test result. The
      results suggest that the practical usefulness of SPECT as a diagnostic adjunct in
      patients suspected of having mild AD is confined to situations in which, on
      clinical grounds, there is considerable diagnostic doubt.

PMID- 8145916
TI  - Clinical and biochemical features of 10 adult patients with muscle phosphorylase
      kinase deficiency.
AB  - Ten adult patients complained of exercise intolerance; five of them had cramps
      and three had recurrent myoglobinuria. Resting serum CK was increased in five.
      Muscle biopsies showed phosphorylase b kinase (PbK) deficiency, whereas the
      activities of other enzymes of carbohydrate metabolism were normal. None of the
      patients exhibited symptoms indicative of liver PbK deficiency. Thus, these
      patients are new additions to a class of PbK glycogen storage disease
      characterized by enzyme deficiency in muscle but not liver. Family histories were
      consistent with autosomal recessive transmission. Monoclonal antibodies specific
      for the beta and gamma subunits of PbK cross-reacted differentially with muscle
      biopsies from three of these patients, suggesting that this phenotype of PbK
      deficiency is biochemically heterogeneous.

PMID- 8145917
TI  - Very long-chain acyl coenzyme A dehydrogenase deficiency presenting with exercise
      induced myoglobinuria.
AB  - A young man presented with recurrent episodes of muscle pain and myoglobinuria
      after prolonged exercise or fasting. Studies on isolated muscle mitochondria
      showed slow flux through beta-oxidation and the presence of only saturated long
      chain acyl coenzyme A (acyl-CoA) esters. These results strongly suggested a
      defect in the dehydrogenation of long-chain acyl-CoA esters that we confirmed by
      measurement of enzyme activity in muscle and platelet mitochondrial fractions and
      fibroblast homogenates. In all tissues studied from the patient, the enzyme
      activity was approximately 10% of control values with acyl-CoA esters from C16
      C22 as substrates. We investigated the intramitochondrial location of the
      deficient acyl-CoA dehydrogenase by subfractionation of platelet mitochondria
      and, in contrast to the short-chain and medium-chain enzymes, which were
      localized in the soluble fraction, the majority of the acyl-CoA dehydrogenase
      activity with long-chain substrates was in the membrane fraction. These studies
      indicate that in humans, the predominant enzyme catalyzing the dehydrogenation of
      long-chain acyl-CoA esters is membrane-bound and that deficiency of this enzyme
      is a cause of muscle pain and rhabdomyolysis.

PMID- 8145918
TI  - Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in
      postmortem pediatric central nervous tissues.
AB  - In previous studies, using polymerase chain reaction amplification of HIV-1 genes
      directly from pathologic tissues of children who died with AIDS encephalopathy,
      we showed that the reading frame of the HIV-1 regulatory nef gene is open,
      suggesting that the nef protein was expressed. We now show, using
      immunocytochemistry and in situ hybridization with nef-specific probes in
      postmortem pediatric CNS tissues, that nef mRNA and protein are present in up to
      20% of astrocytes in tissue sections selected for extensive histopathology. By
      contrast, HIV-1 structural proteins such as gag and their coding mRNAs are
      present in multinucleated giant cells that harbor productive infection and are
      the hallmark of HIV-1 infection in the CNS. These findings are consistent with
      the nonproductive infection of glial cells observed in vitro, and imply that HIV
      1 infection of astrocytes is restricted to early regulatory gene products, of
      which nef is the best target as it is expressed at high levels and is membrane
      anchored. In developing central nervous tissues of children, restricted and
      latent HIV-1 infection of astrocytes may be extensive and contribute
      significantly to HIV-1 neuropathogenesis.

PMID- 8145919
TI  - HIV-1 infection of subcortical astrocytes in the pediatric central nervous
      system.
AB  - Early reports of pediatric HIV-1-associated neuropathology described the presence
      of viral particles in some astrocytes, implicating direct infection of the
      immature nervous system as a contributing factor to the observed neuropathology.
      Several recent reports suggest that in those astrocytes infected with HIV-1, the
      level of antigenic expression of the proviral genome is below the sensitivity
      limits of conventional histochemical techniques. Identification of these
      astrocytes would instead require the use of a highly sensitive radiolabeled DNA
      or RNA probe for in situ hybridization to detect the persistent viral nucleic
      acids. To test this hypothesis, we examined autopsy tissue from 12 infants and
      children with AIDS-associated encephalopathy for the presence of HIV-1-infected
      astrocytes using combined isotopic in situ hybridization for the detection of
      viral-specific nucleic acids and immunohistochemistry for the identification of
      astrocytes. We detected HIV-1 nucleic acids in astrocytes in subcortical white
      matter from four pediatric patients with moderate to extensive leukoencephalitis.
      While gp41 was detectable only on macrophages and multinucleated giant cells, HIV
      1 Nef protein was present in cells morphologically identified as astrocytes in
      two of these patients, further suggesting that HIV-1 establishes a persistent
      rather than a productive infection in astrocytes. Subcortical astrocytes may
      therefore be an unrecognized reservoir for HIV-1 in the developing nervous system
      of some children with AIDS-associated leukoencephalitis.

PMID- 8145920
TI  - The effect of nerve growth factor, ciliary neurotrophic factor, and ACTH analogs
      on cisplatin neurotoxicity in vitro.
AB  - Cisplatin, used to treat ovarian, bladder, and testicular cancers, causes a
      sensory dose-limiting neuropathy. Preliminary observations in humans and animals
      suggest that nerve damage may be prevented by ACTH analogs, particularly those
      belonging to the melanocortin class, and by nerve growth factor (NGF). We
      established a rat embryo dorsal root ganglion model to study cisplatin
      neurotoxicity. The drug reproducibly inhibited axonal growth at concentrations
      similar to that known to produce toxicity in neurons. The inhibition was
      prevented in a dose-dependent fashion by simultaneous exposure to alpha
      melanocyte stimulating hormone (alpha-MSH) or ACTH but not by excess NGF or
      ciliary neurotrophic factor (CNTF). The ACTH peptides were not effective in
      preventing suramin-induced neurotoxicity in the same model. Drug interaction and
      dose-response studies showed that ACTH and alpha-MSH do not act by potentiation
      of NGF action. ACTH analogs appear to protect against cisplatin-induced
      neurotoxicity directly at the cellular level.

PMID- 8145921
TI  - Induction of visual extinction by rapid-rate transcranial magnetic stimulation of
      parietal lobe.
AB  - We used repetitive, rapid-rate transcranial magnetic stimulation (rTMS) for the
      noninvasive study of visual attention in humans. Six right-handed volunteers
      completed eight blocks of 20 single- and 10 double-visual-stimulus trials. The
      visual stimulus was a single asterisk on the right or left side of a computer
      screen or two asterisks presented simultaneously. The subject had to respond to
      the stimulus by pressing the right or left response key or both keys
      simultaneously. During six of the blocks, we applied focal rTMS in trains of five
      pulses at 25 Hz and 115% of the subject's motor threshold intensity to scalp
      positions O1, O2, P3, P4, T5, or T6. Occipital rTMS led to a large number of
      misses of the contralateral asterisk regardless of whether a single or double
      stimulus was presented. Parietal rTMS did not induce misses of single stimuli but
      led to a large number of misses of the contralateral asterisk in the double
      stimulus condition. The effects of temporal rTMS were inconsistent. We conclude
      that rTMS to the occipital lobe causes a sensory detection block, whereas rTMS to
      the parietal lobe can induce selective extinction of contralateral visual stimuli
      during a simultaneous double stimulus.

PMID- 8145922
TI  - A clinical genetic study of Parkinson's disease: evidence for dominant
      transmission.
AB  - We used a family history questionnaire, semi-structured interview, and personal
      examination of secondary cases to collect data on the prevalence of Parkinson's
      disease (PD) in relatives of patients seen consecutively for 1 year and assessed
      the proportion of secondary cases of PD as a function of pedigree completeness.
      Survival analysis methods were applied to estimate the lifetime risk and age-at
      onset distribution of PD among first-degree relatives of probands. When we
      considered siblings of probands with affected parents, the cumulative risk
      increased significantly over siblings of probands without affected parents,
      suggesting significant familial aggregation in a subset of randomly ascertained
      families. We further analyzed 80 multicase families with two or more affected
      individuals. Age-adjusted segregation ratios approaching 0.5 and similar
      proportions of affected parents and siblings, as well as the distribution of
      ancestral secondary cases, were compatible with an autosomal dominant mode of
      inheritance with reduced penetrance in a subset of PD.

PMID- 8145923
TI  - Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS).
AB  - Cytomegalovirus encephalitis (CMVE) is frequently diagnosed only at postmortem
      because its specific clinical features have not been fully identified. We have
      described the clinical, radiologic, and laboratory features of CMVE in a
      retrospective review of 14 autopsy-confirmed cases of CMVE and compared them with
      a control group of demented acquired immunodeficiency syndrome (AIDS) patients
      without CMVE. CMVE was more common among homosexual men, and a subacute onset was
      more typical (mean duration of presenting symptoms was 3.5 weeks versus 18 weeks
      in demented controls). Median survival times were 4.6 weeks for CMVE and 28 weeks
      for controls. CMVE was accompanied by prominent systemic CMV infection at
      autopsy, including CMV adrenalitis (92%), CMV pneumonitis (42%), systemic
      Mycobacterium avium intracellulare (MAI; 58%), and CMV retinitis (58%).
      Hyponatremia and MAI bacteremia were found in 58% of CMVE cases. Polymerase chain
      reaction (PCR) of CSF samples identified CMV genome in 33% of CMVE cases. CMVE
      was associated with periventricular enhancement on CTs and periventricular
      lesions with meningeal enhancement on MRI scans. CMVE should be particularly
      suspected in homosexual men presenting with subacute encephalopathy who have had
      AIDS for more than 1 year and have a history of systemic CMV infection. Other
      features supporting the diagnosis of CMVE include periventricular lesions,
      hyponatremia, and identification of CMV genome in CSF by PCR.

PMID- 8145924
TI  - Neuropsychological and neuroradiologic correlates of emotional prosody
      comprehension.
AB  - We examined a series of 59 patients with acute stroke lesions for the presence of
      comprehension emotional aprosody. Based on a standardized assessment of
      comprehension of emotional intonation, 29 patients (49%) showed emotional
      aprosody (17% "mild" aprosody [n = 10] and 32% "severe" aprosody [n = 19]).
      Patients with comprehension emotional aprosody showed a higher frequency of
      extinction on double-simultaneous stimulation, anosognosia, and deficits in
      facial emotion comprehension. Patients with comprehension emotional aprosody also
      showed a higher frequency of right-hemisphere lesions involving the basal ganglia
      and the temporoparietal cortex and more severe frontal and diencephalic atrophy.
      Comprehension emotional aprosody was not necessarily associated with poststroke
      depression (PSD) since patients with and without PSD showed similar impairments
      in emotional prosody comprehension.

PMID- 8145925
TI  - Concomitants of visual hallucinations in Alzheimer's disease.
AB  - Visual hallucinations (VH) are the most common hallucinations in Alzheimer's
      disease (AD), but their relationships with other behavioral symptoms and measures
      of cognitive performance are unclear. Using the BE-HAVE/AD, a semistructured
      behavioral inventory, we identified 20/160 AD patients (13%) who were currently
      having VH. Patients with VH performed worse on the Mini-Mental State Examination
      and had more behavioral symptoms than patients without VH. Symptoms particularly
      associated with VH included auditory hallucinations, verbal outbursts, delusions,
      and paranoid ideation. Principal factor analysis of the BEHAVE/AD yielded four
      factors accounting for 47% of the total variance. VH loaded on two factors
      involving symptoms of "paranoia" and "agitation/hallucinations." Our findings
      suggest that VH in AD patients are common, often occur in the presence of
      specific behavioral disturbances, and may have management implications.

PMID- 8145926
TI  - Longitudinal study of brainstem auditory evoked responses in 87 normal human
      subjects.
AB  - We evaluated the reproducibility of brainstem auditory evoked responses (BAERs)
      in 87 normal individuals in a longitudinal study by estimating the correlation
      coefficients and variability of the interpeak intervals and the V/I amplitude
      ratio between trials on the same day and between sessions spaced 2 years apart.
      The highest correlation coefficients occur for the I-V interpeak interval between
      trials on the same day. The coefficients for the I-III and III-V intervals are
      lower, due to the variability of wave III. The correlations between ears done on
      the same day are lower still and are similar to measures obtained from the same
      ear at a 2-year interval. BAERs are more variable than previously believed
      between ears and over time, but not in a manner that is clinically significant
      and can be used longitudinally as a measure of neurologic disease. Finally, we
      provide the sample size required to detect a significant change in interpeak
      intervals.

PMID- 8145927
TI  - Amorphous material of the skin in amyotrophic lateral sclerosis: a morphologic
      and biochemical study.
AB  - We performed morphologic studies on skin from seven patients with ALS and seven
      control subjects. By light microscopy, the wide spaces that separated collagen
      bundles reacted strongly with colloidal iron and alcian blue in ALS patients.
      Electron microscopy revealed markedly increased amorphous material that was
      positive for ruthenium red in the ground substance. These findings were not
      present in controls. Quantitative amino acid analysis showed that the amount of
      total amino acids (nmoles per mg dry weight) was significantly decreased (p <
      0.01) in ALS patients compared with that of controls, and there was a significant
      negative correlation between skin amino acid content and duration of illness in
      ALS patients (r = -0.83, p < 0.001). These morphologic findings and biochemical
      data indicate that the amorphous material, which is markedly increased in ALS
      skin, includes glycosaminoglycans.

PMID- 8145928
TI  - Unusual expression and very mild course of Xp21 muscular dystrophy (Becker type)
      in a 60-year-old man with 26 percent deletion of the dystrophin gene.
AB  - A 54-year-old farmer with a negative family history had had mild proximal
      weakness for the previous 4 years. Clinical examination showed marked scoliosis,
      barrel-shaped chest, diffuse hypotrophy, and mild proximal weakness. Creatine
      kinase was 938 U/l; electrocardiography and echocardiography were normal. EMG
      disclosed myopathic changes. Muscle biopsy showed slight, nonspecific
      alterations. Dystrophin was present and normally distributed with antibodies
      against the C-terminal and N-terminal, whereas it was not recognized by the
      antibody against the rod domain. Western blotting detected an abnormal molecular
      weight protein of 320 kd (normal, 427 kd). Southern blot analysis revealed a
      deletion from exon 21 to exon 44, corresponding to 26% of the coding region of
      dystrophin. Six years' follow-up did not disclose progression of the muscle
      disease.

PMID- 8145929
TI  - Clozapine: a 2-year open trial in Parkinson's disease patients with psychosis.
AB  - We treated 17 patients with Parkinson's disease (PD) complicated by psychosis
      with the atypical antipsychotic drug, clozapine, for 6 to 24 months (mean, 15
      months) in a prospective, open-label trial. At 3-month intervals we evaluated
      patients, using a simplified brief Psychiatric Rating Scale (PRS), the motor
      examination portion of the Unified Parkinson's Disease Rating Scale, and the Mini
      Mental State Examination (MMSE). Mean PRS score was significantly improved when
      compared with baseline over 1 year (p < 0.01) and nonsignificantly improved for
      the second year. We maintained the levodopa dose at levels that were 17 to 68%
      higher than baseline, and the mean motor examination score improved by 11 to 22%
      in the first 15 months. Clozapine dosage utilized in the trial ranged from 6.25
      mg every other day to 150 mg/d. Adverse effects, including sedation and
      confusion, were common. These results demonstrate that clozapine therapy can be
      effective in treating psychosis in PD patients over 1 to 2 years. The decline in
      efficacy in the second year was most likely related to an increase in daily
      levodopa dose, progression of dementia (illustrated by a decline in MMSE score),
      and an inability of PD patients to tolerate higher doses of clozapine.

PMID- 8145930
TI  - Conjugal amyotrophic lateral sclerosis: a report on two couples from southern
      France.
AB  - We report two conjugal cases of amyotrophic lateral sclerosis (ALS) occurring
      between 1977 and 1991 in southern France (Languedoc-Roussillon). Although
      conjugal ALS may occur by chance, the description of two cases in the same area
      points to a role of environmental or genetic factors in the etiology of the
      disease.

PMID- 8145931
TI  - A double-blind, placebo-controlled study of the efficacy of thiamine
      hydrochloride in a seasonal ataxia in Nigerians.
AB  - We report the results of the first double-blind, placebo-controlled trial of the
      efficacy of thiamine hydrochloride in a seasonal ataxic syndrome of unknown
      etiology, endemic to the southwestern part of Nigeria. Thiamine produced a
      clinically impressive and statistically significant improvement in clinical
      severity grading in patients with the seasonal ataxia compared with placebo
      (MANOVA, df = 1, F = 35.087, p < 0.0001), with a significant time-treatment
      interaction (MANOVA, df = 3, F = 32.36, p < 0.0001). These results provide
      confirmation for the role of thiamine deficiency in the etiology of the seasonal
      ataxic syndrome and represent the first advance in the elucidation of the
      etiology of this syndrome.

PMID- 8145932
TI  - Concurrent cerebral venous sinus thrombosis and myeloradiculopathy in Sjogren's
      syndrome.
AB  - A 41-year-old woman complained of severe headaches and developed quadriparesis
      and neurogenic bladder. Evaluation disclosed the presence of Sjogren's syndrome
      complicated by myeloradiculopathy with MRI evidence of cervical cord involvement.
      Concurrent cerebral venous sinus thrombosis was also noted. Treatment with
      steroids and warfarin led to clinical improvement and resolution of MRI findings.

PMID- 8145933
TI  - Mitochondrial encephalomyopathy: elevated visual cortex lactate unresponsive to
      photic stimulation--a localized 1H-MRS study.
AB  - We used localized H-magnetic resonance spectroscopy (MRS) to study the metabolic
      changes in the visual cortex of patients with mitochondrial encephalomyopathy.
      Measurement of metabolite levels in the occipital visual cortex obtained in the
      dark with seven normal subjects and with four patients (all four of whom had
      Kearns-Sayre syndrome [KSS]) showed high lactate levels in the patients. Photic
      stimulation (PS) in four normal volunteers showed that lactate increased
      immediately after the start of PS and that it decreased to the baseline level
      with continued PS. Lactate in the resting state was higher in the KSS patients
      than in the controls, and, unlike the controls, the KSS patients showed no
      significant elevation of lactate with PS.

PMID- 8145934
TI  - Syndrome of continuous muscle fiber activity and plasmacytoma with IgM
      paraproteinemia.
AB  - A patient with IgM-lambda plasmacytoma presented with continuous muscle fiber
      activity syndrome (CMFAS), which responded to carbamazepine therapy. This is the
      first report of CMFAS in association with plasmacytoma and IgM paraproteinemia.

PMID- 8145935
TI  - Assessment: melodic intonation therapy. Report of the Therapeutics and Technology
      Assessment Subcommittee of the American Academy of Neurology.

PMID- 8145936
TI  - Sudden 'stroke-like' onset of hemiparesis due to bacterial brain abscess.

PMID- 8145937
TI  - Rapid growth of intracranial aneurysms secondary to cardiac myxoma.

PMID- 8145938
TI  - Lack of anti-Coxiella burnetii seropositivity in patients with HTLV-I-associated
      myelopathy.

PMID- 8145939
TI  - Treatment of paroxysmal symptoms in multiple sclerosis with ibuprofen.

PMID- 8145940
TI  - Tissue transplants for PD.

PMID- 8145941
TI  - Ballismus and mania.

PMID- 8145942
TI  - HIV myelopathy.

PMID- 8145943
TI  - Cyclophosphamide and MS.

PMID- 8145944
TI  - Periventricular nodular heterotopia.

PMID- 8145945
TI  - Bismuth encephalopathy.

PMID- 8145946
TI  - Temporal lobe hypometabolism.

PMID- 8145947
TI  - Psychogenic myoclonus.

PMID- 8145948
TI  - Nevus of Ota.

PMID- 8145949
TI  - Now, more than ever.

PMID- 8145950
TI  - In the wake of Hurricane Andrew: the development of a community-based primary
      care center.

PMID- 8145952
TI  - Amelia Greenwald: pioneer in international public health nursing.

PMID- 8145951
TI  - Healing at home.

PMID- 8145953
TI  - Alaska's watched pot.

PMID- 8145954
TI  - Gertrude Weld Peabody: unsung patron of public health nursing education.

PMID- 8145955
TI  - HLA class I gene, antigen and haplotype frequencies in New Zealand Maori and
      Europeans.
AB  - AIM: To determine class I HLA gene, antigen and haplotype frequencies for New
      Zealand Maori and Europeans. METHODS: Statistical analysis was performed using
      accumulated data from Maori (n = 576) and European (n = 1747) parentage studies.
      RESULTS: HLA class I gene, antigen and haplotype frequencies are as tabulated.
      Significant statistical differences were shown to exist between New Zealand
      Maori, New Zealand Europeans and Europeans. Gene frequencies of HLA A1, 3, 9, 11,
      19 and HLA B7, 8, 12, 16, 22, and 40 differed significantly between New Zealand
      Maori and New Zealand European data. Gene frequencies of HLA A1 and B12 differed
      significantly between New Zealand European and European data. CONCLUSIONS: This
      HLA frequency data can be used for calculating more reliable indices of paternity
      or for determining the potential availability of matched organs for
      transplantation, as well as for anthropological studies. The data may also be
      useful in forensic investigations.

PMID- 8145957
TI  - Education of children with human immunodeficiency virus infection: guidelines for
      families, health care and education personnel. Infection and Immunisation
      Committee of the New Zealand Paediatric Society.

PMID- 8145956
TI  - Predicting disease severity in rheumatoid arthritis.

PMID- 8145958
TI  - A double blind study of itraconazole vs griseofulvin in patients with tinea pedis
      and tinea manus.
AB  - AIM: To compare the efficacy and safety of itraconazole and griseofulvin in a
      double-blind parallel study of 20 patients with microscopically and/or culturally
      proven tinea pedis and/or tinea manus. METHODS: A 4 week study was undertaken
      with patients randomised to receive either itraconazole 100 mg or griseofulvin
      500 mg once daily for 4 weeks. Microscopy and cultures were performed prior to
      and at the end of the treatment and 2 weeks posttreatment. RESULTS: After 4 weeks
      therapy, 50% of itraconazole-treated patients and 30% of griseofulvin-treated
      patients had negative microscopy; 70% and 50% of these patients, respectively,
      had negative microscopy at follow up 2 weeks later. A combined score of all
      clinical assessments showed a statistically significant (p < 0.05) difference at
      the follow up visit in favour of itraconazole. There was no statistically
      significant difference with regard to haematological or biochemical measurements,
      or in urinalysis results, either within or between treatment groups. Six patients
      reported mild adverse effects (itraconazole = 5, griseofulvin = 1), none of which
      warranted treatment withdrawal. CONCLUSION: The findings of this study suggest
      that itraconazole is more effective than griseofulvin in the symptomatic
      treatment of tinea pedis and/or manus.

PMID- 8145959
TI  - The results of a telephone health advice and information service February-March
      1993.
AB  - AIMS: To present analysis of a five week test market telephone health advice and
      information service for the New Zealand public. METHODS: Following a positive
      response from a questionnaire mailing, a service was developed with nurses
      answering telephone health queries using simple diagnostic software and health
      databases. This was advertised in four small New Zealand centres by direct mail.
      The types of calls received, their duration, timing, numbers, and program use was
      recorded. RESULTS: The service was utilised at an overall rate of 0.272 calls per
      hour. The average call lasted 4.36 minutes with peak use between 8 am and noon.
      Calls tended to last longer in the late afternoon. Question topic was most often
      a symptom, followed by disease information, drug effects and poisonings. Callers
      also requested information on injuries, the locations of healthcare providers,
      medical tests and diet. The most useful program in providing this information was
      a small home medical advice program followed by a compact disc library.
      CONCLUSION: While insufficiently popular to warrant continuation with such a
      small target population, this type of service could be a valuable addition to
      health care services if extended nation-wide. Callers were most concerned
      regarding symptoms and diseases. They had more use for this service in mornings,
      when they may have called to make decisions regarding a trip to their usual care
      provider. Afternoon calls lasted longer, perhaps indicating additional concern on
      the part of callers considering the impending evening.

PMID- 8145960
TI  - Severe iron deficiency anaemia in Fiji children.
AB  - AIMS: A prospective study to determine the magnitude of the problem of severe
      iron deficiency anaemia in Fiji children with intercurrent illnesses and their
      response to the interventions with dietary modifications and iron therapy.
      METHODS: A total of 2136 consecutive children between 6 months and 12 years of
      age, who attended a hospital and a health centre in Fiji, for intercurrent
      illness, during a 9 months period, were screened for severe iron deficiency
      anaemia (haemoglobin < 70 g/L). RESULTS: Eighty children (3.7%) had severe iron
      deficiency anaemia. Majority (75%) of children with severe anaemia were younger
      than 2 years. Dietary and iron therapy were successful in correcting anaemia in
      all 80 children. CONCLUSIONS: Severe iron deficiency anaemia was common in Fiji
      children seeking medical attention for intercurrent illness. Simple therapeutic
      measures, which included dietary advice and iron therapy, were successful in
      correcting this severe debility in those children.

PMID- 8145961
TI  - Cultural issues facing medical research in New Zealand: short report of an asthma
      pilot study.

PMID- 8145962
TI  - An unusual cause of polyhydramnios: congenital gastric teratoma.

PMID- 8145963
TI  - Maori health research.

PMID- 8145964
TI  - Mammography for younger women.

PMID- 8145965
TI  - Mammography for younger women.

PMID- 8145966
TI  - Public health in New Zealand.

PMID- 8145967
TI  - Actions of fluoxetine.

PMID- 8145968
TI  - Forensic sampling and medical ethics.

PMID- 8145969
TI  - Hormone replacement therapy.

PMID- 8145970
TI  - Hib catch up as an audit opportunity.

PMID- 8145971
TI  - HTLV1 related cutaneous T cell lymphoma.

PMID- 8145972
TI  - Syndrome X.

PMID- 8145973
TI  - Alcohol intervention.

PMID- 8145974
TI  - Alcohol and violence against women.

PMID- 8145975
TI  - Dangers of concentrated laundry washing powder.

PMID- 8145976
TI  - Biochemical effects of viscoelastic materials on the glycosaminoglycans in the
      organ-cultured rabbit trabecular meshwork.
AB  - We studied the effects of viscoelastic materials on the glycosaminoglycan (GAG)
      profiles in the organ-cultured rabbit trabecular meshwork (TM). The cultured
      specimens were divided into 4 groups: (1) control group; (2) 1% sodium
      hyaluronate-(Na-HA)-treated group; (3) 3% chondroitin-6-sulfate (CD6S)-treated
      group, and (4) 1% methylcellulose (MC)-treated group. They were cultured for 2
      weeks and subjected to sequential enzymatic degradation. In the 1% Na-HA-treated
      group, the proportion of hyaluronic acid was significantly increased compared
      with the control group. In the 3% CD6S-treated group, the proportion of
      chondroitin sulfate was significantly increased compared with the control group.
      In the 1% MC-treated group, the GAG profile did not differ from the control
      profile.

PMID- 8145977
TI  - High-resolution perimetry of the central visual field.
AB  - The Octopus Program M1 was designed for the detection/follow-up of central or
      paracentral visual field defects in patients with neurological disorders or with
      macular or perimacular diseases. Within the central 25 degrees visual field, 59
      test locations provide a resolution of < or = 1.4 degrees. The differential light
      sensitivity is measured with 'Octopus normal strategy', i.e. a 4/2/1 staircase
      procedure. The Program M2X has 81 test locations in the central 10 degrees,
      giving even higher resolution (< or = 0.7 degrees) of the central visual field.
      Both programs have 2 phases, the second being a re-test. Program M2X's phases are
      divided into 4 stages and allow interruption anytime.

PMID- 8145978
TI  - Eye injuries from traditional sports in Aosta Valley.
AB  - We reviewed the records of the patients hospitalised for eye injuries in Aosta
      Valley between January 1976 and June 1993. Eye injuries from traditional regional
      sports accounted for 27 cases (41.5% of all ocular sport injuries), of which 21
      (77.8%) occurred during the game 'tsan', the most popular one. Injuries led to
      legal blindness in 3 (11.1%) cases and to a permanent visual loss in 2 (7.4%).
      Although our data do not allow to assess either a significantly higher incidence
      or severity of eye injuries from Aosta Valley regional games as compared with
      other sports, the possibility of severe trauma with visual loss suggests to
      extend the use of protection devices.

PMID- 8145979
TI  - Transformation of IR spectra of the human lens capsule due to traumatic lens
      subluxation and correlation with the excised and dried lens capsule under
      different treatments.
AB  - Transformation of the secondary conformational structure of the human lens
      capsule after traumatic lens subluxation in a patient was investigated by Fourier
      transform infrared (FT-IR) microscopic spectrometry. The result was compared with
      the IR spectra of type IV collagen in crystalline state, solid film and aqueous
      solution and those of the excised and dried lens capsule under compression or
      treated with ethyl alcohol. The results indicate that the IR spectra of the
      intact human lens capsule after traumatic lens subluxation were the same as those
      of the rabbit lens capsule, except in the 1,100-1,000 cm-1 proteoglycan region,
      but were different from those of type IV collagen aqueous solution at the amide I
      and II bands and the proteoglycan region, although type IV collagen is a
      predominant component of lens capsule. Two new peaks at 1,054 and 1,023 cm-1
      appeared on the IR spectra of the intact human lens capsule and on those of type
      IV collagen in crystalline state and solid film after compression but not in
      normal rabbit lens capsule and native type IV collagen. It was also found that
      all the IR spectra of the excised and dried lens capsule were similar to those of
      native type IV collagen in crystalline state and solid film.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8145980
TI  - Clinical symptoms at different ages in autosomal dominant retinitis pigmentosa. A
      family study in three generations.
AB  - A family with autosomal dominant retinitis pigmentosa in three generations was
      studied. The age of the patients varied from 11 to 66 years. From the youngest to
      the eldest member of the family, the visual acuity varied from 1.0 to 0.4, the
      defect in the visual fields from a relative ring scotoma to a tubular field of 5
      degrees, and the rod threshold in dark adaptation from normal to an elevation of
      3 log units. Color vision was normal in all of the family members. The fundus
      changes varied from coarseness of retinal pigment epithelium to bone spicule
      pigmentation with narrow vessels and pale optic nerve head. The progression of
      autosomal dominant retinitis pigmentosa has been reported to be milder than in
      the other types of retinitis pigmentosa. The clinical symptoms of the family in
      the present study confirm this finding.

PMID- 8145981
TI  - Branch retinal vein occlusion and exudative retinal detachment: pathogenetical
      aspects.
AB  - Exudative retinal detachment (ERD) is an uncommon complication of branch retinal
      vein occlusion (BRVO). The ERD pathogenesis has been mainly related to the
      haemodynamic overload and to an impairment in the function of the retinal pigment
      epithelium. Data relative to 98 cases of BRVO without ERD were compared with the
      correspondent data of 10 cases of BRVO with ERD. Venous leakage showed a
      substantial equivalency between the two groups, while evaluation of retinal
      venous collaterals demonstrated a lower amount in the BRVO cases with ERD, with a
      statistically significant difference. Moreover, considering the various ERD
      localizations, we suggest that the ERD pathogenesis is mainly ascribable to the
      scant development of retinal venous collaterals but that an important role may
      also be played by the retinal pigment epithelium impairment consequent to the
      retinal ischaemia.

PMID- 8145982
TI  - A comparison of the ocular hypotensive efficacy and systemic safety of 0.5%
      levobunolol and 2% carteolol.
AB  - In a 3-month, double-masked, randomized clinical trial, the ocular hypotensive
      efficacy and systemic safety of 0.5% levobunolol and 2% carteolol were compared
      in 59 patients with open-angle glaucoma or ocular hypertension. The overall mean
      decrease in intraocular pressure was 7.3 mm Hg (27.4%) in the 0.5% levobunolol
      group and 4.1 mm Hg (14.8%) in the carteolol group. This difference was
      statistically significant (p = 0.0004). Changes in visual field and cup-disk
      ratios were few and similar between the groups. Effects on mean heart rate were
      noted in both treatment groups. The mean decrease in heart rate in the carteolol
      group was greater (-8.4 beats/min) than in the levobunolol group (-3.1
      beats/min). This difference had marginal statistical significance (p = 0.059). We
      conclude that 0.5% levobunolol and 2% carteolol administered twice daily differ
      in lowering intraocular pressure as well as in their effects on heart rate.

PMID- 8145983
TI  - Epidermal growth factor in the topical treatment of herpetic corneal ulcers.
AB  - The tolerability and efficacy of epidermal growth factor (EGF) in the topical
      treatment of herpetic corneal ulcers in addition to topical acyclovir have been
      evaluated in a double-blind, placebo-controlled, randomized study in two groups
      of patients. The time required for complete reepithelialization of the cornea was
      recorded, and the data obtained were analyzed statistically. In the EGF group,
      the reepithelialization was significantly faster than in the control group.
      Tolerability of EGF was always excellent. These results indicate that EGF is safe
      and effective in reducing the healing time of herpetic corneal ulcers.

PMID- 8145984
TI  - Detection of varicella-zoster virus DNA in conjunctivas of patients with herpes
      zoster.
AB  - Detection of varicella-zoster virus (VZV) DNA was carried out in the conjunctivas
      of 18 patients with herpes zoster by polymerase chain reaction. The rate of VZV
      DNA detection in conjunctivas was 3/4 in herpes zoster ophthalmicus associated
      with eruption on the dorsum nasi, 2/5 in herpes zoster ophthalmicus without
      eruption on the dorsum nasi, 1/2 in herpes zoster with eruption on the cheek and
      lower jaw, 1/2 in generalized herpes zoster and 0/5 in herpes zoster associated
      with eruption on the trunk or extremities, respectively. The reason for the
      detection of VZV DNA in conjunctivas is discussed.

PMID- 8145985
TI  - Paranoid hallucinations following ocular surgery.
AB  - Paranoid hallucinations were seen in 2 patients following ocular surgery.
      Following his second cataract surgery, a 77-year-old male patient became
      disorientated, suffered paranoid hallucinations and fractured his first lumbar
      vertebra 'falling' from the balcony of the first floor. A 79-year-old female
      suffered from paranoia and visual hallucinations following goniotrephination
      surgery.

PMID- 8145986
TI  - Sebaceous gland carcinoma of the eyelid presenting as a conjunctival papilloma.
AB  - A 70-year-old man complained of the sensation of having a foreign body in his
      left eye in June 1992. A papillary tumor was found growing from the palpebral
      conjunctiva of the left upper eyelid. On June 30, the conjunctival tumor was
      excised: the histopathologic findings indicated a malignancy. On August 18, full
      thickness excision of the upper eyelid, including the rest of the tumor, was
      performed. Histopathologic findings showed a well-differentiated sebaceous gland
      carcinoma. We believe that sebaceous gland carcinoma presenting as conjunctival
      papilloma, as found in our patient, may be uncommon.

PMID- 8145987
TI  - Acute retinal necrosis: a result of immune dysfunction? Report of a case with
      subacute evolution and relapses in a patient with impaired cellular immunity.
AB  - We report an atypical case of acute retinal necrosis (ARN) with a subacute course
      and relapses lasting for more than 4 years in an apparently immunocompetent 71
      year-old female who had been followed for 4.5 years for recurrent retinochoroidal
      lesions with transient exudative retinal detachments and areas of consecutive
      chorioretinal atrophy. The diagnosis of varicella-zoster virus (VZV)-induced ARN
      was finally made on the basis of anterior granulomatous uveitis, typical retinal
      necrosis and the detection of anti-VZV antibodies in the aqueous humor. A
      widespread lumbar zoster dermatitis, cutaneous anergy and depressed in vitro
      lymphocyte activation indicated depressed cellular immunity. Absolute and
      relative numbers of B lymphocytes were increased. It is suspected that depressed
      cellular immunity and maintained B cell function might possibly be at the origin
      of ARN. The protracted course of ARN in this patient also suggests that the
      dysregulation of the immune system has probably existed for a long time.

PMID- 8145988
TI  - [Changes of Glutathione Peroxidase Activity in Eye Tissues of Emory Mice in
      Relation to Cataract Status and Age].
AB  - The relationship between the activity of the antioxidant defense enzyme
      glutathione peroxidase (GSH-PX) and the degree of cataract (lens opacity) was
      examined in 14 Emory mice at the age of 2, 7 and 10 months. Significant decreases
      in specific GSH-PX activity (mU/mg wet tissue) in the lens as well as in the
      residual eye tissue were found between 2 and 10 months of age, showing a highly
      significant correlation of this decrease (r = 0.590, p approximately 0.001) with
      the increasing degree of turbidity of the lenses. The results are discussed with
      regard to the changes of antioxidant mechanisms during cataractogenesis and
      aging. The role of the maintenance of an optimal level of GSH-PX and other well
      known antioxidants (enzymes, vitamins, trace elements including iodide) for a
      delay of cataractogenesis is pointed out.

PMID- 8145989
TI  - A case of oncocytoma in the eyelid.
AB  - Oncocytoma rarely arises from the eyelid and only 2 cases have been reported
      previously. We present a case of oncocytoma in the upper eyelid around the
      lacrimal punctum. Anatomical location and histological findings suggested that
      oncocytes of this tumor originated from the epithelium of Moll's gland or the
      lacrimal canaliculus.

PMID- 8145990
TI  - Ultraviolet transmittance of contact lenses.
AB  - Chronic and acute exposure to ultraviolet (UV) radiation has been shown to have
      deleterious effects on all layers of the human eye. As a consequence, appropriate
      protective measures have been advocated with respect to exposure to this form of
      radiation. Among suggested actions are spending less time in the sun and wearing
      protective visual aids such as those containing UV-absorbing materials when
      exposed to sunlight. To investigate the protective ability of currently available
      contact lens materials we measured the transmittance characteristics of 11
      different types of soft and rigid contact lenses in the UV and visible range from
      280 to 500 nm with a Zeiss model DM4 Dual Beam Spectrophotometer. Our findings
      indicate that lenses not treated with UV absorbers transmitted most of the UV
      radiation. Lenses containing UV absorbers provided excellent UV protection and
      transmitted significantly less UV radiation than the untreated lenses (Student's
      t-test with Bonferoni's correction, N = 10, p < 0.001). Based on our findings, we
      recommend that contact lenses with UV absorbers be considered as a viable option
      for providing UV protection, especially for aphakic patients, patients taking
      photosensitizing pharmaceutical agents, and those patients who spend a great deal
      of time outdoors.

PMID- 8145991
TI  - Early signs of myopia in Chinese schoolchildren.
AB  - We looked for the earliest signs of the onset of myopia in 194 emmetropic (-0.25
      to +0.75 D) eyes by following them for 1 to more than 2 years. Visual acuity
      examination, cycloplegic retinoscopy, and A-scan ultrasonography were performed
      at intervals of 6 to 12 months. Of the 194 eyes 64 became myopic during the
      observation time. Our results show that during the progression from emmetropia to
      myopia the change in visual acuity is not a good indicator of the onset of
      myopia. When visual acuity decreased to below 6/6 (20/20) cycloplegic retinoscopy
      showed that most of the 64 eyes had become truly myopic and A-scan
      ultrasonography revealed a significant increase in vitreous chamber depth and
      axial length as compared to the non-myopic eyes. In the early stage of myopia
      development the anteroposterior diameter of the eye elongates. However, changes
      in anterior chamber depth and lens thickness did not differ between the myopic
      and non-myopic group. Our results suggest that routine ocular refraction should
      be conducted in addition to the school vision screening. For those who have
      visual acuity 6/6 (20/20) and ametropia of -0.25 D or more minus we would like to
      be able to prevent or at least retard the development of myopia.

PMID- 8145992
TI  - S-cone sensitivity in unilateral aphakia.
AB  - BACKGROUND: Exposure to ultraviolet radiation (UVR) and blue light has been shown
      to cause retinal damage in animals. In humans, it has been argued that the loss
      of short-wavelength (S) cone sensitivity during normal aging may be related to
      chronic light exposure. METHODS: We measured sensitivity to blue and yellow
      lights presented on bright yellow backgrounds at several retinal eccentricities
      in both eyes of an observer with long-standing unilateral aphakia. RESULTS: For
      yellow lights, where media absorption is not a major factor, there was a 2-fold
      loss in sensitivity of long (L) and medium (M) wavelength cone mechanisms in the
      aphakic eye relative to the phakic eye. For blue lights detected by S-cones,
      there was a 10-fold loss of S-cone mechanism sensitivity in the aphakic eye,
      after differences in ocular media density were taken into account. CONCLUSIONS:
      Our findings strongly support the hypothesis that chronic exposure to short
      wavelength radiation impairs S-cone function.

PMID- 8145993
TI  - Accuracy of Javal's rule in the determination of spectacle astigmatism.
AB  - Javal's rule and Grosvenor's simplification of it are commonly used formulas for
      predicting spectacle astigmatism from keratometric measurements. We assessed the
      accuracy of these two rules. Spectacle astigmatism was estimated using both rules
      from measurements of corneal astigmatism on 100 eyes of 100 subjects. These
      estimates were then compared to the subjectively determined spectacle
      astigmatism. Grosvenor's simplification of Javal's rule gave slightly more
      accurate assessments than the original rule. However, only 66% of results gave
      estimates within 0.50 D, and 7% differed by more than 1.00 D. This can be
      compared to previous reports on the accuracy of autorefractors, where
      approximately 95% of cylinder results were within 0.50 D of the spectacle
      astigmatism. These results indicate that using Javal's rule or Grosvenor's
      simplification of it to determine spectacle astigmatism from corneal cylinder
      readings is of limited clinical value.

PMID- 8145994
TI  - Measurement of elastic modulus of the central bovine cornea by means of
      holographic interferometry. Part II. Results.
AB  - BACKGROUND: The structural and elastic properties of the cornea play an important
      role in the outcome of corneal refractive surgery. A way to describe the elastic
      properties is to calculate Young's modulus. The tangent Young's modulus (Eit)
      represents the first part of the viscoelastic response of the intact cornea due
      to intraocular pressure increase. METHOD: The tangent Young's modulus (Eit) of
      the central cornea of 16 fresh enucleated intact bovine eyes determined from the
      immediate response was calculated by means of holographic interferometry. The
      stress was an increase of the intraocular pressure. In 16 eyes the change of
      intraocular pressure was 10 Pa (group I), starting with an intraocular pressure
      of 1340 Pa (about 10 mm Hg). In 6 of these 16 eyes there was a second pressure
      increase of 20 Pa starting at the same intraocular pressure of 1340 Pa (about 10
      mm Hg) (group II). RESULTS: The mean value for the Young's modulus in group I was
      1.58 x 10(5) Pa. For group II the Young's modulus was 1.60 x 10(5) Pa. The
      difference was not significant. The values for the Young's moduli of the cornea
      of intact eyes are about 100 times smaller than calculations based on experiments
      with strips of the cornea. CONCLUSION: It is necessary to consider the
      localization of the corneal tissue to avoid influences of corneal hydration or
      dehydration and to define the existing intraocular pressure if Young's modulus of
      the cornea is to be calculated.

PMID- 8145995
TI  - Ocular and facial anthropometry of young adult males of Arab origin.
AB  - Other investigators have provided normal values of facial and ocular dimensions
      of subjects of different ethnic backgrounds. Our main reason for carrying out
      this study was to provide a data base of similar measurements for the male Arab
      (Saudi) population. A projected photographic technique was used. Measurements
      from the photographs were transformed to real life distances by multiplying by a
      constant factor. The results of our investigations show that Japanese have wider
      inter-outer canthal distance (IOCD) than Arabs and Caucasians, both of whom have
      similar IOCD. Arabs have wider inter-inner canthal distance (IICD) than
      Caucasians. African-Americans and Japanese have wider inter pupillary distance
      (IPD) than Arabs. Percentile values of the measured distances will aid in
      syndrome diagnosis among male Arabs.

PMID- 8145996
TI  - An investigation of prism adaptation latency.
AB  - PURPOSE: The latency of adaptation of the human vergence system to a change in
      convergence or divergence forced upon it by a prism was investigated in this
      pilot study. METHODS: Adaptation was stimulated by a 5-s period of binocular
      vision through a prism of 0 delta, -8 delta, or 8 delta. Immediately thereafter
      and for a further period of 45 s, lateral heterophoria was monitored subjectively
      by an automated version of Duane's screen and parallax test. Adaptation was
      calculated from the phoria 40 s after the end of binocular vision. Tests were
      performed at 0.4 m. In the first test session, there was screening during the
      binocular period to test for flaws in the screening method. In the second
      session, there was no screening during the binocular period and phoria
      measurement was started without changing the power of the prism. In the third
      session, the prism was restored to 0 delta after the period of binocular vision.
      Immediately after the last 5-s test, tests were repeated with 1 s of binocular
      vision. The subject had excellent visual acuity, stereoacuity, and stereolatency.
      RESULTS: The test functioned correctly and showed good repeatability. The
      greatest adaptation to 8 delta was 59%. This was obtained with only 1 s of
      binocular vision. There was adaptation to -8 delta with 5 s of binocular vision
      but it was obscured by adaptation to 0 delta or 8 delta which persisted from
      previous tests. DISCUSSION: The reason why the subject's latency was not found
      more precisely is explained. Additional evidence is presented in support of the
      finding that prism adaptation can take place within 1 s (perhaps less) of
      binocular vision, and the persistence and dominance of adaptation to base-out
      prism at near is pointed out. Guidelines are proposed for the experimental
      measurement of prism adaptation latency.

PMID- 8145997
TI  - Clinical evaluation of a portable ultrasonic and a standard optical pachometer.
AB  - The clinical performance of a portable ultrasonic pachometer was compared with a
      modified optical pachometer on a group of normal subjects. The mean central
      corneal thickness according to optical pachometry using the "edge-to-edge" method
      of optical doubling was 0.553 mm (SD = +/- 0.022). The mean central corneal
      thickness using the ultrasonic device was 0.506 mm (SD = +/- 0.039). The
      differences between the means was statistically significant (at 1% level of
      probability). Based on the light distribution within the corneal optical section
      viewed during optical pachometry a hypothesis is derived supporting the notion
      that optical pachometry tends to overestimate corneal thickness rather than
      ultrasonic pachometry underestimating corneal thickness.

PMID- 8145998
TI  - Admission and optometry grade comparisons among students receiving different
      types of admission interviews.
AB  - This retrospective study examined the interview scores, admission grades, and
      optometry grades of students who received one of two types of admission
      interviews. The INDIV-BLIND group (N = 36) represented those students who had
      received an individual interview (i.e., one interviewer) for which the
      interviewer had no access to the candidate's file. The PANEL-ACCESS group (N =
      21) was made up of those students who had received a panel interview (i.e., two
      interviewers) for which the interviewers had access to the candidate's file. The
      two groups were compared using two admission grades and seven optometry grades.
      Both t-test and Wilcoxon Score statistical procedures were used to test the null
      hypothesis (H0) that there were no significant grade differences (p < 0.05)
      between the INDIV-BLIND and PANEL-ACCESS groups. The H0 was accepted. There were
      no indications that the homogeneity of grades in the two groups was a function of
      the admission process. When the interview scores in each group were considered,
      Spearman Correlation Coefficients showed that the interview scores of the PANEL
      ACCESS group significantly correlated (p < 0.05) with six of the academic grades
      such that better scores were associated with higher grades. No such correlations
      were found for the INDIV-BLIND group. The results were interpreted as evidence
      that interviewers can be unduly influenced in their scoring of the interview by
      the candidate's written file. The difference in skills reflected by the interview
      score and the clinic grade was suggested as an important factor in accounting for
      the lack of correlation between these two measures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8145999
TI  - Postinfectious hepatitis B optic neuritis.
AB  - A 41-year-old female nurse's aide presented with a recent history of viral
      hepatitis B. Approximately 1 month after her liver functions had normalized she
      developed symptoms of optic neuritis with painful loss of vision and optic disc
      edema. Her laboratory studies revealed evidence of systemic vasculitis and
      glomerulonephritis. A discussion is presented of the patient's clinical course
      and a brief history of the systemic effects of acute hepatitis B infection (HBV);
      the pathophysiology for HBV-induced autoimmune optic neuritis (ON), management
      guidelines, and differential diagnoses are discussed.

PMID- 8146000
TI  - Hemangioma of the apical orbit diagnosed by radionuclide imaging.
AB  - Hemangiomas are benign vascular hamartomas which occur more commonly in women
      between the ages of 30 and 50 years. These tumors are among the most common
      lesions found in the adult orbit. The purpose of this report is to describe the
      usefulness of delayed blood pool scans for diagnosing unusually located
      hemangiomas as highlighted in our report of a 67-year-old white male who reported
      initially with unilateral proptosis. Computed tomography and magnetic resonance
      imaging showed a distinct mass measuring 1.6 cm anteroposterior diameter by 1.5
      cm width by 1.2 cm height near the apex of the orbit. A gallium scan was negative
      for a solid tumor. A technetium-99 m blood pool (hemangioma SPECT scan) was
      positive, consistent with a hemangioma of the orbital soft tissue.

PMID- 8146001
TI  - Correlation of optotypes with the Landolt ring--a fresh look at the comparability
      of optotypes.
AB  - The legibility of three selected sets of optotypes: (1) letters; (2) Snellen E;
      and (3) KOLT test have been compared to the Landolt ring in a study based on the
      German Standard DIN 58220, Part 2 and the International Standard ISO 8597. The
      letters were printed in the standard typeface used on German street signs (sans
      serif Linear-Antiqua, Typeface B). The main results are: 1. A set of letters can
      be selected in such a way that the differences in legibility displayed between
      different letters in the set are smaller than the ISO/DIN allowance of 0.05
      logarithmic units of the visual angle, although the letters are not constructed
      according to the traditional 5 by 5 or 5 by 4 construction principles. 2. The
      eight letters C, D, E, K, N, P, U, Z are proposed for standardized visual acuity
      tests because of their almost equal legibility. 3. The height of the typeface
      used for this selected set of letters should be 5% less than the diameter of the
      Landolt ring in order to achieve the same legibility as the latter. 4. Both shape
      optotypes (Snellen E and KOLT test) must be approximately 15% smaller than the
      diameter of the Landolt ring in order to obtain comparable visual acuity scores.

PMID- 8146003
TI  - Aniseikonia and intraocular lenses, a continuing saga.

PMID- 8146002
TI  - Contact lens wear, use of eye cosmetics, and Meibomian gland dysfunction.
AB  - The purpose of this study was to explore the interrelations among contact lens
      wear, use of eye make up, eye rubbing, and Meibomian gland dysfunction. Fifty
      optometry students were evaluated for Meibomian gland function (number of lower
      lid glands expressing freely with gentle pressure) and fluorescein staining of
      the cornea and conjunctiva. Subjects were questioned regarding contact lens wear,
      use of eye cosmetics, and frequency of eye rubbing. No relation was detected
      among Meibomian gland clogging, contact lens wear, cosmetic use, or eye rubbing
      in these subjects. The data suggest a relation among clogged glands, contact lens
      wear, and fluorescein staining. Future studies of older contact lens wearers are
      warranted.

PMID- 8146004
TI  - Reducing effective vertical prism in bifocals.

PMID- 8146005
TI  - [First experiences with the new financing system and health care plans].
AB  - Our experience on the new health reimbursement system and further plans for
      secondary care. The author gives a short review about the steps of the health
      reform emphasizing the importance of initiation of performance based
      reimbursement which has supported to reach the aims of our reform. The results of
      the new reimbursement system, its practical difficulties, the actions taken to
      overcome them are also presented. It can be stated that no theoretical objection
      has been arised against the performance based reimbursement. A committee has been
      elected for the necessary continuous maintenance of the system. The equalization
      of the facilities, the reconstruction process of the hospitals, the investments
      financed by the World Bank loans are the conditions of the further reforms. The
      program "For the Healthier Nation" is the most important contribution to our
      health reform. Financially this program based on the "The Health Promotion
      Foundation".

PMID- 8146006
TI  - [Clinical significance of steroid receptors in breast cancer].
AB  - The steroid receptor determination (first of all estrogen receptor--ER--) of the
      breast cancer tissue has become an important factor for prognostication and
      treatment. Authors from the Surgical Department of the National Institute of
      Oncology provide a biostatistical survey of their 727 breast cancer patients.
      Following factors proved to have significant impact on the prognosis: positivity
      of ER, the quantitative value of ER, ER vs. lymph node status, ER vs. DFI, ER and
      the site of metastases and the hormone therapy. The progesterone receptor (PR)
      provides indication in case only for DFI for metastases. However, in this very
      respect it has a more significant value than that of ER. Multidimensional
      analysis has shown that the most important prognostic factors are the lymph node
      status, patient's age, size of the tumour and the ER value.

PMID- 8146007
TI  - [Changes in cervical fibronectin levels during pregnancy, labor and in the
      postpartum period].
AB  - The authors analysed the fibronectin content of the uterine cervix during
      pregnancy and delivery. The aim of their investigation was furnishing data to the
      biochemical changes during cervical maturation. The ripening of the uterine
      cervix during pregnancy is a result of complicated interactions between different
      macromolecules, where the fibronectin plays a key role. The quantitative
      determination of the extracellular matrix fibronectin is impossible because its
      extraction from tissues recently is not solved. Taking this fact in consideration
      the authors choose a semiquantitative method, being reliable indicator of changes
      in fibronectin content of uterine cervix. They took small pieces of materials
      from portio vaginalis uteri of 139 women being in postmenopause and premenopause,
      in different stages of pregnancy and parturition concerning directly after
      delivery. The slides were incubated, with rabbit-anti-human fibronectin-FITC. The
      evaluation of fluorescence happened with an Axiophot (Zeiss) microscope. Authors
      stated that the fibronectin content in the cervical extracellular matrix and in
      the cellular membrane of fibroblasts increases during the 1st trimester
      pregnancy. This increase can be shown in the 3rd trimester as well and it drops
      significantly during delivery. They could not found any relationship between the
      leucocyte invasion observed during delivery and the changes of cervical
      fibronectin content. These observations call our attention to the importance of
      fibronectin in cervical ripening respectively dilatation and the need of further
      examinations.

PMID- 8146008
TI  - [Correlation between adhesive factors of primary hemostasis and liver
      fibrogenesis in alcoholic live cirrhosis].
AB  - Colchicine administration is able to reduce collagen production and the
      fibrogenetic process in alcoholic liver diseases in the same time. The decrease
      of the serum lipid peroxidation capacity along with type III procollagen
      propeptide level was associated with the simultaneous reduction of plasmatic von
      Willebrand factor, fibronectin and beta-thromboglobulin levels. This observation
      suggest a connection between the regulation of primary haemostasis and liver
      fibrogenesis.

PMID- 8146009
TI  - [The role of the Batthyany family in medical history].

PMID- 8146010
TI  - [The fate of the Hungarian University School of Pharmacy after resettlement to
      Germany].

PMID- 8146011
TI  - [Midwifery--a "profession" with long-standing history].

PMID- 8146012
TI  - Mechanisms of oxalate absorption and secretion across the rabbit distal colon.
AB  - To further evaluate the mechanisms of oxalate (Ox2-) transport in the intestine
      the following studies were performed using isolated, short-circuited segments of
      the rabbit distal colon (DC). In control buffer, the DC absorbed Ox2- (net Ox2-
      flux, JNetOx = 5.4 +/- 0.7 pmol.cm-1.h-1). Replacement of Na+ with N-methyl-D
      glucamine (NMDG+) abolished Ox2- absorption by decreasing mucosal to serosal Ox2-
      flux (JmsOx), without affecting Cl- transport, while gluconate substitution for
      Cl- did not affect JNetOx or net Na+ flux (JNetNa). Addition of Na+ to the
      serosal side of tissues bathed by NMDG+ buffer increased JmsOx 40% without
      altering mucosal to serosal Cl- flux (JmsCl). Serosal amiloride or dimethyl
      amiloride (10(-3) M) abolished JNetOx by decreasing JmsOx, it increased serosal
      to muscosal Cl- flux (JsmCl) and it gradually inhibited short-circuit current
      (Isc). Mucosal amiloride (10(-4) M) abolished Ise but had no effect on Ox2- or Cl
      fluxes. Serosal 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 10(-6)
      M) reduced JmsOx by 20% and JNetOx by 43% without affecting JmsCl or JNetCl.
      Dibutyryl cyclic adenosine monophosphate (dB-cAMP, 5 x 10(-4) M, both sides)
      stimulated Ox2- secretion (JNetOx = -12.6 +/- 3.3 pmol.cm-2.h-1). The dB-cAMP
      induced secretion of Ox2- and Cl- were fully abolished by serosal furosemide (10(
      4) M) and partially inhibited (35%) by 5 x 10(-4) M mucosal NPPB [5-nitro-2-(3
      phenylpropylamino)-benzoic acid], a putative Cl- channel blocker.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8146013
TI  - Colonic-crypt-derived epithelia express induced ion transport differentiation in
      monolayer cultures on permeable matrix substrata.
AB  - The processes of transport differentiation from stem cell to the terminally
      differentiated cell in intact colonic crypts are difficult to study because
      access to the lumen is limited. Colonocytes were isolated from the lower two
      thirds of rat distal colon crypts and grown to confluence on reconstituted
      basement membranes and permeable support in primary culture. Crypt and surface
      cells were distinguished by the uptake of [3H]thymidine and [3H]leucine and by
      brushborder fluorescence binding. Ion concentrations in apical and basolateral
      compartments of filter monolayer cultures after 48 h of incubation on days 16-18
      were (in mM): apical, Na+ 116 +/- 4 (n = 48) and K+ 6 +/- 1 (n = 48);
      basolateral, Na+ 151 +/- 3 and K+ 3.7 +/- 0.5, respectively (mean +/- SE).
      Aldosterone (10(-8) M), added to the basolateral compartment from days 10-18,
      changed apical Na+ to 72 +/- 6 mM and apical K+ to 13 +/- 4 mM (n = 23).
      Dexamethasone (10(-8) M) changed apical Na+ to 84 +/- 7 mM but did not influence
      apical K+ (n = 22). Transmonolayer electrical potential difference (VtM; control
      medium; days 8-10) was 5 +/- 1 mV (n = 16; apical compartment negative);
      electrical resistance (RtM) was 217 +/- 21 omega.cm2 and short circuit current
      (ISC) was 21 +/- 5 microA.cm-2. Amiloride (0.1 mM; n = 12) in the apical medium
      decreased VtM to 2 +/- 1 mV and ISC to 11 +/- 4 microA.cm-2. Aldosterone (10(-8)
      M) after 1 week in the basolateral compartment (n = 21) changed VtM to 12.3 +/- 3
      mV, RtM to 92 +/- 9 omega.cm2, and ISC to 138 +/- 23 microA.cm-2. Apical
      amiloride (0.1 mM; n = 9) decreased the induced VtM to -3 +/- 1 mV and ISC to -13
      +/- 7 microA.cm-2. Colonic-crypt-derived epithelial cells proliferate and
      differentiate in primary culture, when grown on reconstituted basement membrane
      substratum and in supplemented medium, to form monolayers that express net Na+
      absorption and net K+ secretion after 1 week. Na+ and K+ vectorial transport
      differentiation is primarily regulated by aldosterone, which specifically induces
      apical conductive Na+ transfer. Mineralocorticoid and glucocorticoid hormones
      appear to have differing actions on ion transport in functionally surface-type
      colonocytes derived in culture from isolated crypt-type cells.

PMID- 8146014
TI  - Effects of caffeine on intracellular calcium, calcium current and calcium
      dependent potassium current in anterior pituitary GH3 cells.
AB  - Caffeine elicits physiological responses in a variety of cell types by triggering
      the mobilization of Ca2+ from intracellular organelles. Here we investigate the
      effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and ionic
      currents in anterior pituitary cells (GH3) cells. Caffeine has a biphasic effect
      on Ca(2+)-activated K+ current [IK(Ca)]: it induces a transient increase
      superimposed upon a sustained inhibition. While the transient increase coincides
      with a rise in [Ca2+]i, the sustained inhibition of IK(Ca) is correlated with a
      sustained inhibition of the L-type Ca2+ current. The L-type Ca2+ current is also
      inhibited by other agents that mobilize intracellular Ca2+, including thyrotropin
      releasing hormone (TRH) and ryanodine, but in a matter distinct from caffeine.
      Unlike the caffeine effect, the TRH-induced inhibition "washes-out" under whole
      cell patch-clamp conditions and is eliminated by intracellular Ca2+ chelators.
      Likewise, the ryanodine-induced inhibition desensitizes while the caffeine
      induced inhibition does not. Simultaneous [Ca2+]i and Ca2+ current measurements
      show that caffeine can inhibit Ca2+ current without changing [Ca2+]i. Single
      channel recordings show that caffeine reduces mean open time without affecting
      single-channel conductance of L-type channels. Hence the effects of caffeine on
      ion channels in GH3 cells are attributable both to mobilization of intracellular
      Ca2+ and to a direct effect on the gating of L-type Ca2+ channels.

PMID- 8146015
TI  - Na+/amino acid coupling stoichiometry of rheogenic system B0,+ transport in
      Xenopus oocytes is variable.
AB  - Using electrophysiological and radiotracer studies in parallel, we have
      investigated the characteristics of the endogenous Na(+)-dependent amino acid
      transporter (system B0,+) in Xenopus oocytes with regard to ion dependence,
      voltage dependence and transport stoichiometry. In voltage-clamped oocytes (-60
      mV) superfusion with saturating concentrations of amino acids (1 mM) in 100 mM
      NaCl resulted in reversible, inward currents (mean +/- SEM): alanine, 1.83 +/-
      0.09 nA (n = 21); arginine, 2.54 +/- 0.18 nA (n = 17); glutamine, 1.73 +/- 0.10
      nA (n = 19). Only arginine evoked a current in choline medium (0.50 +/- 0.13 nA,
      n = 10), whereas Cl- replacement had no effect on evoked currents. The glutamine
      evoked current was saturable (Imax = 1.73 nA, glutamine Km = 0.12 mM) and
      linearly dependent upon voltage between -90 and -30 mV. Using direct and indirect
      (activation) methods, we found that transport can proceed with Na+/amino acid
      coupling stoichiometry of either 1:1 or 2:1, but coupling was the same for each
      amino acid tested (alanine, arginine and glutamine) within a batch of oocytes
      (i.e. from a single toad). Despite the net single positive charge on arginine,
      the magnitude of the net transmembrane charge movement during Na(+)-coupled
      arginine transport was identical to that for the zwitterionic neutral amino acids
      glutamine and alanine; this may be explained by a concomitant stimulation of K+
      efflux during arginine transport with a putative coupling of 1 K+:1 arginine.

PMID- 8146016
TI  - Species variants of the IsK protein: differences in kinetics, voltage dependence,
      and La3+ block of the currents expressed in Xenopus oocytes.
AB  - We have compared the slowly activating K+ currents (IsK) resulting from the
      expression of the human, mouse, or rat IsK proteins in Xenopus oocytes, utilizing
      natural, species-dependent sequence variations to initiate structure-function
      studies of this channel. Differences were found between the human and rodent
      currents in their voltage dependence, kinetics, and sensitivity to external La3+.
      The current/voltage relationships of the human and rat IsK currents differed
      significantly, with greater depolarizations required for activation of the human
      channel. The first 30 s of activation during depolarizations to potentials
      between -10 and +40 mV was best described by a triexponential function for each
      of the three species variants. The activation rates were, however, significantly
      faster for the human current than for either of the rodent forms. Similarly,
      deactivation kinetics were best described as a biexponential decay for each of
      the species variants but the human currents deactivated more rapidly than the
      rodent currents. The human and the rodent forms of IsK were also differentially
      affected by external La3+. Low concentrations (10, 50 microM) rapidly and
      reversibly reduced the magnitude of the mouse and rat currents during a test
      depolarization and increased the deactivation rates of the tail currents. In
      contrast, the magnitude and deactivation rates of the human IsK currents were
      unaffected by 50 microM La3+.

PMID- 8146017
TI  - Modification of cardiac sodium current by intracellular application of cAMP.
AB  - We examined the effects of intracellular perfusion of cyclic adenosine
      monophosphate (cAMP) on the sodium current (INa) of guinea-pig ventricular
      myocytes, using the whole-cell clamp technique. INa was elicited by depolarizing
      voltage steps (-20 mV) from a variety of holding potentials (-120 to -50 mV),
      under conditions of 60 mM extracellular Na+ concentration ([Na+]o) and at the
      temperature of 24-26 degrees C. Intracellular perfusion of cAMP decreased the INa
      elicited from the holding potentials less negative than -90 mV. In the presence
      of 1 mM cAMP, for example, the peak INa elicited from -80 mV decreased from 6.0
      +/- 2.0 nA to 4.0 +/- 2.2 nA (mean +/- SD, P < 0.02, n = 7) within 3-6 min. In
      the presence of extracellular 3-isobutyl-1-methylxanthine (IBMX, 20 microM), much
      lower concentrations of cAMP (0.2 mM) yielded a comparable effect. On the other
      hand, intracellular perfusion of cAMP increased the INa elicited from very
      negative holding potentials (< -100 mV). For instance, the application of cAMP (1
      mM) increased the INa elicited by step depolarizations from -120 mV (to -20 mV),
      from 9.9 +/- 2.1 nA to 11.0 +/- 3.1 nA (P < 0.05, n = 5). The former effect was
      attributed to a marked shift of the steady-state inactivation curve of INa to the
      negative direction; the voltage of half-inactivation shifted from -77.9 +/- 1.0
      to -83.5 +/- 1.4 mV, or by -5.6 mV. The latter effect may be explained by
      increases in maximum available conductance of INa.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8146018
TI  - Compensatory effects of chronic electrostimulation on unweighted rat soleus
      muscle.
AB  - The purpose of this study was to investigate the effects of electrostimulation in
      counteracting the transformation of the unweighted rat soleus muscle. The
      stimulation resembled the firing patterns of normal slow motor units and was
      imposed during hindlimb suspension. For the 10-day hindlimb suspended rats, the
      transformation of the slow soleus muscle towards a faster type was characterized
      by a decrease in the time to peak tension and the half-relaxation time of the
      twitch, a reduction in the P20/P0 index, i.e. the ratio of the subtetanic tension
      at 20 Hz relative to the tetanic tension, and a decrease in the percentage
      distributions of type I fibres accompanied by an increase of type IIa and IIc
      fibres. These changes were prevented by electrostimulation since, for the
      parameters mentioned above, no significant difference was observed in the soleus
      of the suspended rats that received electrostimulation when compared with the
      control rats. Nevertheless, neither the loss of mass nor the decrease in force
      output in the suspended rats were prevented by electrostimulation. The present
      results suggest a positive compensation of the suspension-induced alterations in
      the contractile and histochemical properties of the soleus muscle by means of
      chronic electrostimulation, which, however, do not prevent atrophy or the loss of
      contractile force.

PMID- 8146019
TI  - Intracellular calcium modulates basolateral K(+)-permeability in frog skin
      epithelium.
AB  - Cytosolic calcium ([Ca2+]i) has been suggested as a key modulator in the
      regulation of active sodium transport across electrically "tight" (high
      resistance) epithelia. In this study we investigated the effects of calcium on
      cellular electrophysiological parameters in a classical model tissue, the frog
      skin. [Ca2+]i was measured with fura-2 in an epifluorescence microscope setup. An
      inhibition of basolateral potassium permeability was observed when cytosolic
      calcium was increased. This inhibition was reversible upon removal of calcium
      from the serosal solution.

PMID- 8146020
TI  - Different properties of caffeine-sensitive Ca2+ stores in peripheral and central
      mammalian neurones.
AB  - Using indo-1 based microfluorometry for measuring the cytoplasmic free calcium
      concentration ([Ca2+]i), the properties of caffeine-induced Ca2+ release from
      internal stores were studied in rat cultured central and peripheral neurones,
      including dorsal root ganglia (DRG) neurones, neurones from nucleus cuneatus, CA1
      and CA3 hippocampal region and pyramidal neocortical neurones. Under resting
      conditions the Ca2+ content of internal stores in DRG neurones was high enough to
      produce caffeine-triggered [Ca2+]i transients. Caffeine-induced Ca2+ release
      depleted internal stores in DRG neurones, but they refilled themselves
      spontaneously up to 81.4 +/- 5.67% within 10 minutes. In contrast, in all types
      of central neurones the resting Ca2+ content of internal stores was low, but the
      stores could be charged by transmembrane Ca2+ influx through voltage-operated
      calcium channels. After charging, the stores in central neurones spontaneously
      lost releasable calcium content and within 10 minutes they emptied again. We
      suggest that in sensory neurones calcium stores are continuously filled by
      releasable calcium and after discharge they can refill themselves spontaneously,
      while in central neurones internal calcium stores can be charged by releasable
      calcium only transiently.

PMID- 8146021
TI  - Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is
      inhibited by protein kinase C.
AB  - To define the role of protein kinase C (PKC) in oxygen-dependent production of
      erythropoietin (EPO) in the liver, we have determined EPO messenger ribonucleic
      acid (mRNA) expression in primary cultures of juvenile rat hepatocytes incubated
      at different oxygen tensions in the absence and presence of phorbol esters,
      vasopressin, and structurally different kinase inhibitors. Upon reduction of
      oxygen concentrations from 40% to 3% EPO mRNA in cultured hepatocytes increased
      markedly within 1.25 h, reached maximal values after 2.5 h and remained elevated
      for up to 72 h. Treatment of hepatocytes during 1.25-5 h of hypoxic exposure with
      phorbol 12-myristate-13 acetate (PMA) attenuated hypoxia-induced EPO mRNA levels
      dose-dependently by a maximum of approximately 50%. This inhibitory effect of PMA
      disappeared upon treatment for more than 5 h and was completely lost after
      incubation for 9 and 18 h in the presence of 10(-6) M and 10(-7) M PMA,
      respectively. Phorbol 12,13-dibutyrate and vasopressin also inhibited EPO mRNA
      accumulation, whereas 4 alpha-phorbol 12,13-didecanoate was ineffective. Western
      blot analysis of PKC isozymes revealed the presence of PKC alpha, beta II, delta,
      epsilon and zeta and provided no evidence that the PMA-induced inhibition of EPO
      expression was associated with depletion of any of these isozymes. Conversely,
      PMA-induced inhibition of EPO mRNA accumulation was paralleled by translocation
      of PKC alpha from cytosol to membranes and the time- and dose-dependent
      attenuation of the inhibitory effect of PMA on EPO mRNA levels was paralleled by
      down-regulation of PKC alpha. A dose-dependent inhibition of EPO mRNA formation,
      independent of effects on total RNA synthesis, as determined by [3H]uridine
      incorporation, was also found in the presence of the kinase inhibitor
      staurosporine (ED50 approximately 2 x 10(-8) M) and three structurally related
      derivatives with increased selectivity for PKC (RO 317549, ED50 approximately 1 x
      10(-6) M; RO 318220, ED50 approximately 1 x 10(-6) M and CGP 41251, ED50
      approximately 4 x 10(-6) M). The markedly lower potency of the latter three
      compounds as compared to staurosporine suggests that this suppression of EPO gene
      induction was not mediated by inhibition of PKC. In summary the data indicate
      that PKC alpha is a negative modulator of EPO gene expression in hepatocytes. A
      kinase other than PKC, however, appears to be an essential element of hypoxic
      signalling.

PMID- 8146022
TI  - Polymyxin B has multiple blocking actions on the ATP-sensitive potassium channel
      in insulin-secreting cells.
AB  - The action of polymyxin B (0.1 microM) on ATP-sensitive K+ (K+ATP) channels in
      RINm5F insulin-secreting cells was investigated by patch-clamp techniques. Using
      inside-out patches, open-cells and outside-out patches, polymyxin B was found to
      block K+ATP channels by, on average, approximately 90-95% of the initial control
      level of channel activity. The effects were rapid in onset, sustained and readily
      reversible. Similar effects were found in patches excised from cells pretreated
      overnight with 1 microM of the phorbol ester phorbol myristate acetate (PMA).
      External block of channels was associated with a marked decrease in single
      channel current amplitude, whereas these effects were not seen when polymyxin B
      was added to the inside face of the membrane. In patches bathed with internally
      applied ATP (0.5 mM) and ADP (0.5 mM), polymyxin B inhibited channels but its
      actions were not reversible upon removal of the compound. However, when the same
      protocol was undertaken upon cells pre-treated with PMA, the effects of polymyxin
      B were readily reversed. Our data suggests that polymyxin B is a novel modulator
      of K+ATP channels, exhibiting multiple blocking actions that may possibly involve
      a direct effect upon the channel and indirect effects mediated through the
      inhibition of endogenous protein kinase(s).

PMID- 8146023
TI  - Dissociation between brown adipose tissue thermogenesis and sympathetic activity
      in rats with high plasma levels of oestradiol.
AB  - It has been shown previously that high plasma levels of oestradiol inhibit brown
      adipose tissue thermogenesis. Since rats and mice show a close association
      between thermogenic activity in and sympathetic discharge to brown fat, we
      measured the noradrenaline turnover in rats with high plasma levels of oestradiol
      to establish whether the observed inhibition of thermogenic activity is brought
      about by a reduction in the sympathetic drive to brown adipocytes. Oestradiol
      filled Silastic capsules were implanted subcutaneously in female rats previously
      acclimated either to thermoneutrality or to cold. Control rats received empty
      implants. After 15 days treatment, noradrenaline turnover was measured by
      blocking its synthesis with alpha-methyl-p-tyrosine. As expected, noradrenaline
      turnover was higher in cold-acclimated rats than in rats kept at
      thermoneutrality. The presence of high plasma oestradiol levels did not alter
      sympathetic activity in any of the treated groups despite reducing thermogenic
      activity. This result reveals that oestradiol dissociates the thermogenic
      activity of brown adipose tissue from its sympathetic activation. Such
      dissociation has never been previously reported in rats, although it seems to be
      common in Syrian hamsters. However the causative factor in this species is
      unknown.

PMID- 8146024
TI  - Effects of ischaemia and post-ischaemic reperfusion on the passive and active
      electrical parameters of rat skeletal muscle fibres.
AB  - Electrical parameters of extensor digitorum longus (EDL) muscles and their
      contralaterals were measured "in vitro" at 30 degrees C by a computerized two
      intracellular microelectrode technique after ischaemia and post-ischaemic reflow.
      In some muscles the adenosine triphosphate (ATP) levels are also measured.
      Ischaemia led to a 39% reduction of Cl- conductance (GCl), whereas reperfusion
      increase GCl by 18% with respect to contralateral control muscles. Ischaemia and
      reperfusion increased K+ conductance (GK) by 21% and 68%, respectively; this
      increased was reversed by 50 microM glybenclamide, suggesting an involvement of
      ATP-sensitive K+ channels. A statistically significant hyperpolarization and
      increase in excitability was observed after ischaemia, whereas after the reflow
      period the fibres were depolarized and less excitable. Ischaemia and reperfusion
      lowered the intracellular ATP content by 18% and 64%, respectively.

PMID- 8146025
TI  - Low-Pi diet increases the abundance of an apical protein in rat proximal-tubular
      S3 segments.
AB  - Dietary phosphate (Pi) restriction is associated with an adaptive increase in
      proximal-tubular apical brush-border membrane (BBM) sodium-dependent Pi transport
      (Na-Pi cotransport). Adaptation to Pi restriction is dependent on de novo protein
      synthesis; however, it is not known whether the proteins involved represent newly
      synthesized Na-Pi cotransporters or some other (regulatory) proteins. Recently
      the cDNA for a Na-Pi cotransport system of rabbit kidney cortex (system NaPi-1)
      has been identified by expression cloning. The purpose of this study was to
      determine if the adaptive increase in Na-Pi cotransport in response to dietary Pi
      restriction in the rat is associated with an increase in the abundance of a NaPi
      1-related protein. To answer this question we took advantage of the cross
      reactivity of polyclonal antibodies raised against a C-terminal peptide of the
      NaPi-1 protein with a protein of BBM isolated from rat kidney cortex. On Western
      blots, a positive reaction with a protein with an apparent molecular mass of 100
      kDa was observed in BBM isolated from juxtamedullary cortex and, to a lesser
      extent, in BBM isolated from superficial cortex. In immunohistochemical studies
      anti-(NaPi-1)-antiserum-mediated immunofluorescence was observed predominantly in
      S3 segments where the immunoreaction was restricted to the brush borders.
      Compared to control BBM, in BBM isolated from the juxtamedullary cortex of rats
      fed a low-Pi diet, there was a twofold increase in the abundance of the 100-kDa
      protein. In the same membrane vesicles Na-Pi cotransport was increased threefold.
      The results of this study demonstrate specific expression of a 100-kDa apical
      protein in S3 cells of rat proximal tubules. Increased abundance of the 100-kDa
      protein due to chronic Pi restriction suggests an involvement of this protein in
      the (chronic) adaptive response of S3 cells to a low-Pi diet.

PMID- 8146026
TI  - Three distinct types of voltage-dependent K+ channels are expressed by Muller
      (glial) cells of the rabbit retina.
AB  - There is ample evidence that retinal radial glial (Muller) cells play a crucial
      role in retinal ion homeostasis. Nevertheless, data on the particular types of
      ion channels mediating this function are very rare and incomplete; this holds
      especially for mammalian Muller cells. Thus, the whole-cell variation of the
      patch-clamp technique was used to study voltage-dependent currents in Muller
      cells from adult rabbit retinae. The membrane of Muller cells was almost
      exclusively permeable to K+ ions, as no significant currents could be evoked in
      K(+)-free internal and external solutions, external Ba2+ (1 mM) reversibly
      blocked most membrane currents, and external Cs+ ions (5 mM) blocked all inward
      currents. All cells expressed inwardly rectifying channels that showed
      inactivation at strong hyperpolarizing voltages (> or = -120 mV), and the
      conductance of which varied with the square root of extracellular K+
      concentration ([K+]e). Most cells responded to depolarizing voltages (> or = -30
      mV) with slowly activating outward currents through delayed rectifier channels.
      These currents were reversibly blocked by external application of 4-aminopyridine
      (4-AP, 0.5 mM) or tetraethylammonium (TEA, > 20 mM). Additionally, almost all
      cells showed rapidly inactivating currents in response to depolarizing (> or = 
      60 mV) voltage steps. The currents were blocked by Ba2+ (1 mM), and their
      amplitude increased with the [K+]e. Obviously, these currents belonged to the A
      type family of K+ channels. Some of the observed types of K+ channels may
      contribute to retinal K+ clearance but at least some of them may also be involved
      in regulation of proliferative activity of the cells.

PMID- 8146027
TI  - Local anaesthetic-like effect of interleukin-2 on muscular Na+ channels: no
      evidence for involvement of the IL-2 receptor.
AB  - The effects of interleukin-2 (IL-2) on muscular Na+ currents were studied in
      human myoballs. The transient Na+ inward currents, elicited by repetitive
      depolarizations at 1 Hz and recorded in the whole-cell mode, were inhibited by
      the cytokine, the half-maximum effect occurring at about 500 U/ml. The effects
      resembled those of local anaesthetics without use dependence, as the inactivation
      (h infinity) curve was shifted in a negative direction while the current/voltage
      curve was not affected. As with these local anaesthetics, depolarization at 1, 4
      and 8 Hz in the presence of IL-2 did not produce any cumulative block. The
      interaction of IL-2 with the Na+ channels is very fast (within ms) and it is
      suggested that it occurs when the Na+ channels are in the state of fast
      inactivation. The recovery from inactivation was only slightly slowed by IL-2, in
      agreement with the absence of any use dependence. All effects were readily
      reversible on washout of the cytokine. The effects were seen both in tetrodotoxin
      (TTX)-sensitive adult Na+ channels and in TTX-insensitive juvenile channels. In
      contrast to the whole-cell configuration, no inhibition was visible in the
      attached-patch configuration. Further, the preincubation with an anti-IL-2
      receptor antibody did not prevent the inhibitory effect of IL-2 on the Na+
      currents. It is concluded that the cytokine blocks the voltage-dependent muscular
      Na+ channels by keeping the channels in the state of fast inactivation. An IL-2
      receptor and a second messenger system are not likely to be involved in this
      reaction.

PMID- 8146028
TI  - Continuous fluorometric measurement of intracellular pH and Ca2+ in perfused
      salivary gland and pancreas.
AB  - Intracellular pH (pHi) has been measured in intact, perfused rat mandibular
      salivary glands loaded with the fluorescent pH indicator BCECF [2',7'-bis(2
      carboxyethyl)-5(6)- carboxyfluorescein]. Glands mounted in the cuvette of a
      conventional bench-top spectro-fluorometer were perfused for 5 min with the
      acetoxymethyl ester of BCECF and fluorescence was measured ratiometrically at 6-s
      intervals. The mean value of pHi in glands perfused with a HCO3(-)-free, N-2
      hydroxyethylpiperazine-N'-2- ethanesulphonic acid (HEPES)-buffered solution at 37
      degrees C was 7.36 +/- 0.01 (n = 52) which is comparable with values obtained by
      31P nuclear magnetic resonance (NMR) spectroscopy. NMR data confirmed that the
      BCECF loading period was accompanied by a transient acidification of the cells,
      but there was no significant change in the content of the major phosphorus
      metabolites. Changes in pHi in response to NH4Cl pulses and acetylcholine
      stimulation were comparable with results reported previously for isolated acini.
      Additional, preliminary experiments show that the method can also be used to
      monitor intracellular Ca2+ (using fura-2) in perfused salivary glands, and can be
      adapted for studies of the isolated, perfused pancreas.

PMID- 8146029
TI  - Hexose transport across the apical and basolateral membrane of enterocytes from
      different regions of the chicken intestine.
AB  - The properties of hexose transport across the apical and basolateral membranes of
      chicken enterocytes have been studied in the small and large intestine. Results
      show that (a) isolated epithelial cells from all segments except the coprodeum
      can accumulate 3-O-methylglucose (Glc3Me) against a concentration gradient, by a
      Na(+)-dependent and phloridizin-sensitive mechanism. (b) The cell cumulative
      capacity for Glc3Me (control/phloridizin-incubated cells) is lower in the small
      intestine than in the large intestine (rectum = proximal caecum = ileum > jejunum
      > duodenum). (c) Theophylline enhances the cell Glc3Me cumulative capacity 2.9
      fold in the duodenum and 2.4-fold in the jejunum but has no effect in the other
      segments studied. (d) Analysis of sugar uptake indicates that net hexose influx
      rates decrease from proximal to distal regions: jejunum > duodenum > ileum =
      proximal caecum = rectum for the apical transport system (alpha-methyl glucoside
      as substrate and phloridizin as inhibitor) and duodenum > jejunum > ileum =
      proximal caecum = rectum for the basolateral system (2-deoxyglucose;
      theophylline). (e) The duodenum and the jejunum show high apical and basolateral
      hexose transport rates, which confer a significant capacity for sugar absorption
      on the proximal intestine. More distal regions, including the ileum, the proximal
      caecum and the rectum, have transport systems analogous to those of the proximal
      intestine that keep a considerable potential capability to recover hexoses from
      the lumen.

PMID- 8146030
TI  - Cell transformation induces a cytoplasmic Ca2+ oscillator in Madin-Darby canine
      kidney cells.
AB  - Alkaline stress transforms Madin-Darby canine kidney (MDCK) cells as indicated by
      loss of epithelial structure, multilayer cell growth and formation of foci. In
      the present study we report that transformed MDCK cells (MDCK-F cells) exhibit
      spontaneous and lasting oscillations of intracellular Ca2+ concentration
      ([Ca2+]i), which are absent in non-transformed cells. Oscillations, as revealed
      by Fura-2 video imaging, were due to the activity of an inositol 1,4,5
      trisphosphate-(InsP3)-sensitive Ca2+ store since their frequency was dependent on
      bradykinin concentration and they were abolished by the phosphoinositidase C
      inhibitor U73122. Moreover, blockers of the cytoplasmic Ca(2+)-ATPase,
      thapsigargin and 2,5-di-(tetr-butyl)-1,4-benzohydroquinone inhibited oscillatory
      activity. In contrast, neither injection of ruthenium red, ryanodine nor caffeine
      had any effect on oscillations. Analysis of the spatial distribution of [Ca2+]i
      showed that Ca2+ transients originated from an initiation site constant for a
      given cell and spread through the cell as an advancing Ca2+ wave. Oscillations
      started in a random manner from single cells and spread over neighbouring cells,
      suggesting a kind of intercellular communication. We conclude that MDCK-F cells
      have acquired the ability for endogenous Ca2+ release through transformation.
      Oscillations are primarily due to the activity of an InsP3-sensitive cytosolic
      Ca2+ oscillator.

PMID- 8146031
TI  - Cytoplasmic Ca2+ determines the rate of Ca2+ entry into Mardin-Darby canine
      kidney-focus (MDCK-F) cells.
AB  - Transformed Mardin-Darby canine kidney-focus (MDCK-F) cells exhibit spontaneous
      Ca2+ oscillations from an inositol 1,4,5-triphosphate-sensitive cytoplasmic Ca2+
      store. In this study, Ca2+ entry from the extracellular space and its role in
      generation of oscillations were investigated by means of Ca2+ video imaging and
      the Fura-2/Mn2+ quenching technique. Oscillations were dependent on extracellular
      Ca2+ concentration and were inhibited by extracellularly applied La3+, Co2+ and
      Ni2+. Depolarization of the cell membrane with high K+ concentrations and the L
      type Ca2+ channel blocker nifedipine had no effect on oscillations, indicating
      the lack of involvement of voltage-gated Ca2+ channels. Mn2+ quenching
      experiments disclosed significant Ca2+ influx into MDCK-F cells. The rate of this
      influx was constant between Ca2+ spikes, but markedly increased during the
      spontaneous Ca2+ spikes. Similar transient increases in Ca2+ entry could be
      mimicked by agents triggering intracellular Ca2+ release such as bradykinin and
      thapsigargin. We conclude that the plasma membrane of MDCK-F cells exhibits a
      marked voltage-independent Ca2+ permeability permitting Ca2+ entry into the
      cytoplasm. The rate of Ca2+ entry which determines the frequency of oscillations
      is most likely to be regulated by the cytoplasmic Ca2+ concentration.

PMID- 8146032
TI  - [Is percutaneous ablation the alternative for other methods of treatment of
      paroxysmal recurrent tachyarrhythmias?].

PMID- 8146034
TI  - [Levels of endothelin and atrial natriuretic peptide (ANP) in plasma of patients
      with chronic renal failure treated by hemodialysis].
AB  - Two groups of subjects were studied. The group A consisted of 40 patients treated
      by HD (haemodialysis) (mean age--x +/- SEM 38.6 +/- 1.47 years, duration of
      haemodialysis treatment 36.8 +/- 3.7 months, cuprophan dialyzers and acetate
      containing solution--38 mEg/l--were used, time of HD--4 hours 3 times weekly,
      predialysis serum creatinine was 900.8 +/- 32.1 mumol/l (10.2 +/- 0.4 mg%)
      postdialysis serum creatinine was 467.8 +/- 28.3 mumol/l (5.3 +/- 0.3 mg%).
      Patients were not treated with erythropoietin. The control group comprised 20
      healthy subjects (mean age 36.7 +/- 2.7 years and serum creatinine level 76.7 +/-
      3.5 mumol/l (0.9 +/- 0.1 mg%). In all examined subjects the following
      experimental protocol was used. In both group blood pressure (BP) and heart rate
      (HR) were determined at about 8 a.m. after an overnight rest. Then blood samples
      were withdrawn for estimation of ANP, endothelin, haematocrit value (Ht),
      haemoglobin (Hb) and creatinine concentrations. Between 8 and 12 a.m. all
      examined subjects of the group A were dialysed. After each hour of dialysis BP
      and HR were measured and blood samples were withdrawn ANP (Peninsula Lab.Kids.)
      and endothelin (Amersham Kids) were measured using RIA methods, but other
      biochemical parameters using routine methods. Serum creatinine and plasma ANP
      levels significantly decreased after HD. Plasma endothelin level was
      significantly higher than in the control subjects. After first hour of HD a
      significant decrease of plasma endothelin was observed and than plasma endothelin
      level started to increase. No significant correalations between creatinine, ANP
      and endothelin levels in examined group was observed.

PMID- 8146033
TI  - [Effect of maprotiline on bronchodilation in patients with bronchospasm].
AB  - The bronchodilatory effect of maprotiline (Ludiomil, firm Ciba-Geigy) was
      investigated in 20 patients with bronchospasm (FEV %below 60%). The effect of a
      single dose of 75 mg maprotiline was compared with that produced by 500 mg of
      aminophylline, applied each time in 500 ml normal saline during 90 min, on two
      different days, in randomized sequence, always at the same day time. Prior to and
      at 5, 10, 20, 30, 60, 90, 120, 150 and 180 minutes after commencement of the
      infusion the following parameters of pulmonary ventilation have been determined:
      VC, FEV1, FEV1%., MEFR and MBC. The stated differences between the efficacy of
      maprotiline and aminophylline were statistically not significant (p > 0.05). In
      18 patients maprotiline caused sedation and even somnolence. The authors conclude
      that maprotiline is an efficacious bronchodilator in patients with bronchospasm
      and is well tolerated by the patients.

PMID- 8146035
TI  - [Secretion of insulin and peptide C in workers exposed to whole body vibration
      and noise].
AB  - Insulin and C-peptide concentrations were studied in serum (by means of
      radioimmunoassay) after an oral glucose tolerance test in 62 workers
      occupationally exposed to whole body vibration and noise, and in 30 non-exposed
      workers of the control group. In the exposed group more frequent occurrence of
      higher glucose and insulin concentrations, with normal C-peptide concentrations,
      were found. The observed non-effective hyperinsulinaemia is likely caused by an
      impaired insulin degradation in the liver and/or an increased production of
      proinsulin which is assayed simultaneously by IR-I method.

PMID- 8146036
TI  - [Lupus anticoagulant--mysterious procoagulant].

PMID- 8146037
TI  - [Evaluation of diagnostic sensitivity using ARA criteria in 108 patients with
      systemic lupus erythematosus studied retrospectively].
AB  - We studied usefulness of ARA criteria for the classification of sle in 108
      outpatients with diagnosis established during long term follow-up. Sensitivity of
      ARA criteria was 96.3% and excluding tests for anti dsDNA and anti Sm antibodies
      was 93.5%. That means less than 10% false negative diagnoses. When at least 2 ARA
      criteria are present immunological tests of high specificity should confirm the
      diagnosis.

PMID- 8146038
TI  - [Behcet's syndrome with esophageal and intestinal involvement].
AB  - A case of 22-years old man with Behcet's syndrome is presented. Apart from
      typical aphtous ulcers in the mouth and on the scrotum the patient had
      oesophageal ulcerations and inflammatory changes in the ileum. During 8 years
      follow up the patient had several bleeding episodes from the gastrointestinal
      tract that required blood transfusions.

PMID- 8146039
TI  - [Prospectives of anti-adhesion therapy].

PMID- 8146040
TI  - [Professor Antoni Gluzinski: life and achievements of the founder of of the
      Polish Archives of Internal Medicine].

PMID- 8146041
TI  - [Atrial natriuretic peptide (ANP)--its role under physiologic conditions and
      certain clinical conditions].

PMID- 8146042
TI  - [Effect of intravenous infusions of theophylline on cardiac arrhythmias and
      activity of creatinine kinase CK-MB in patients with airway obstruction].
AB  - The effect of intravenous theophylline upon the activity of creatinine kinase
      (CK) and its cardiac specific isoenzyme compound (CK-MB) and the frequency of
      cardiac arrhythmias was evaluated in 12 patients with bronchial asthma and
      spastic bronchitis. The patients were receiving an intravenous infusion of
      theophylline for three days. On the first day twice (400 mg and 300 mg) and
      subsequently, 400 mg once daily over 30 minutes. Measurements of the peak
      expiratory flow (PEF) were obtained prior to theophylline administration,
      immediately after the infusion and at 1, 3 and 6 hours while serum theophylline
      levels were determined at the same time by enzyme immunoassay. Continuous 24-h
      Holter monitoring the electrocardiogram was performed. CK-MB elevation was
      observed related to the theophylline infusion. The CK-MB activity prior to
      theophylline administration was 10.87 +/- 5.2 units and 24.9 +/- 13.4 units at 5
      min after termination of the infusion. The elevation was sustained until the end
      of the observation period, being 29.4 +/- 17 units at 1 hour, 27.95 +/- 12.1
      units at 3 hours and 34.9 +/- 13.9 at 6 hours. On the third day of the study,
      although theophylline had been withheld for 24 hours the baseline CK-MB levels
      were found to be higher than on day 1, at 14.35 +/- 5.35 (the difference,
      however, was not statistically significant) and the activity increased after each
      theophylline infusion (21.7 +/- 6.7 units, 22.5 +/- 5.7 units, 23.6 +/- 5.5 units
      and 28.2 +/- 7.3 units respectively). No statistically significant differences in
      CK activity were found. In most patients the heart rate was accelerated during
      the theophylline infusion and four patients developed clinically silent
      ventricular arrhythmias obviously related to the infusion. In one patient a five
      hour long bout of atrial fibrillation, which resolved spontaneously was observed.
      No changes were found in the ST-T segment. The ventricular arrhythmias correlated
      with the increased activity of CK-MB and were related to the serum theophylline
      levels. The study confirms a potential cardiotoxic effect of intravenous
      theophylline with a resultant requirement of careful adjustment of doses.

PMID- 8146043
TI  - [Distribution of phospholipids in platelet membranes and platelet factor 3
      availability in patients with chronic kidney failure].
AB  - Patients with end-stage renal failure (ESRF) have a defect of haemostasis mainly
      caused by disturbances of platelet vessel wall interactions. An essential part in
      platelet function is played by the membrane phospholipids. The aim of this study
      was to estimate phospholipid distribution in platelet membrane and to evaluate
      the correlation between this distribution and PF3 availability. 18 non-dialysed
      (group I) and 21 chronically haemodialysed patients (group II) were studied.
      Phospholipid distribution was determined using TNBS tracer by the Vale method,
      and by phospholipase hydrolysis according to the modified Chap method. PF3
      availability was estimated by the Saleem method. In group I membrane phospholipid
      distribution was unchanged as compared with control group, in this group
      decreased PF3 availability was also shown. In group II higher content of
      phosphatidylserine (PS) and phosphatidylethanolamine (PE) at the outer surface of
      platelet membrane was observed as compared with the healthy persons. In this
      group increased PF3 availability correlated with PS and PE exposition was also
      noted. It may reflects platelet activation in these patients. The different PF3
      availability in non-dialysed and chronically haemodialysed patients suggests
      various pathogenesis of haemostasis disturbances in their patients.

PMID- 8146044
TI  - [The ankle-arm index and whole blood viscosity in patients with type II diabetes
      mellitus with ischemia of the lower extremities].
AB  - The relationship was studied between the ankle-arm index (K/R) and whole blood
      and plasma viscosity in patients suffering from diabetes mellitus type II with
      ischemia of lower extremities. The measurements were carried out in 96 patients
      (80 males and 16 females), of whom 72 were in stage II of Fontaine progression.
      Immediately after determination of the K/R index blood was taken from vena
      mediana cubiti adding Na2EDTA for rheological test. Whole blood viscosity was
      measured with a Low-Shear 100 Contraves viscometer immediately after sampling,
      and plasma viscosity was measured with a capillary viscometer of Ubbvelohd within
      2 hours after sampling. By the method of regression analysis and linear
      correlation it was found that increased whole blood and plasma viscosity
      significantly correlated with reduced K/R value in the patients. The obtained
      results are analysed in biophysical and clinical aspects.

PMID- 8146045
TI  - [Urinary excretion of hepatitis B virus antigens, antibodies against HB virus and
      proteins precipitating in polyethylene glycol in patients with acute and chronic
      hepatitis].
AB  - The presence of antigens of HB virus and excretion of antibodies against the
      compounds of this virus in the urine of patients with acute and chronic hepatitis
      B was shown by the use of precipitation of polyethylenic glycol 6000 (PEG) and
      the immunoenzymatic method. The main compound of precipitating complexes in PEG
      excreted with the urine is the HBe antigen detected in the urine of patients both
      with acute and chronic virus B hepatitis.

PMID- 8146046
TI  - [Relationship between renal biopsy histopathology and profile of changes in serum
      protein, lipids and proteinuria in patients with nephrotic syndrome due to
      chronic glomerulonephritis].
AB  - Relationship was assessed between the type of renal pathology and the degree of
      plasma protein and lipid abnormalities in 59 patients with nephrotic syndrome due
      to chronic glomerulonephritis (GN). All patients were divided into 5 subgroups
      according to the type of renal pathology (extracapillary proliferative GN--23,
      mesangioproliferative GN--18, membranous GN--5, minimal changes--5, other--8
      patients) and according to the presence (22 patients) or absence (37 patients) of
      altered interstitium (inflammation and/or fibrosis). In all patients the
      following parameters were analyzed: plasma levels of creatinine, total
      cholesterol and lipids, triglycerides, total protein, electrophoretic fractions
      of plasma proteins and urinary protein excretion. Type of renal pathology as well
      as presence of interstitial lesion did not influence the degree of protein and
      lipid abnormalities in nephrotic patients. Significantly more marked (p < 0.05)
      abnormalities in the serum and lipid profile were found in patients in whom 76
      100% of all glomeruli were abnormal than in patients with a lower percentage of
      damaged glomeruli. CONCLUSION: Percentage of damaged glomeruli but not the type
      of renal pathology (glomerular or/and interstitial) are the main factors
      influencing the magnitude of abnormal serum protein and lipid profiles in
      nephrotic patients.

PMID- 8146047
TI  - [Atrial fibrillation--frequent cause of cerebral stroke].

PMID- 8146048
TI  - [Clinical analysis of cardiac arrhythmias in patients with chronic renal failure
      treated conservatively. I. Evaluation of cardiac arrhythmias].
AB  - On in-patient basis 24-hr electrocardiographic Holter monitoring was performed in
      20 patients with chronic renal failure (c.r.f.) on conservative treatment (10
      women and 10 men, aged 43.6 +/- 9.8 years), in 10 patients with chronic primary
      glomerulonephritis without arterial hypertension and renal failure (2 women and 8
      men, aged 34.2 +/- 10.5 years), and in 10 patients with primary arterial
      hypertension without clinical symptoms of renal disease (1 woman and 9 men, aged
      36.6 +/- 9.5 years). No atrio-ventricular conduction disturbances were found in
      patients with c.r.f. Supraventricular and ventricular arrhythmias occurred in 90%
      of the patients. Ventricular arrhythmias were observed in 8% of c.r.f. patients.
      Among them simple ventricular extrasystoles (Lown 0-3) predominated and they were
      found in 65% of the patient. Numbers of ventricular extrasystoles were small and
      amounted to 44.7 per 24 hrs. Cardiac arrhythmias registered in both comparative
      groups were not different from those found in c.r.f. patients. The results
      suggest that chronic renal failure in patients on conservative treatment does not
      peculiarly predispose to the occurrence of cardiac arrhythmias.

PMID- 8146049
TI  - [Clinical analysis of cardiac arrhythmias in patients with chronic renal failure
      treated conservatively. II. Evaluation of the relationship between cardiac
      arrhythmias and some echocardiographic indices--preliminary investigations].
AB  - Cardiac arrhythmias detected during 24-hr electrocardiographic Holter monitoring
      were correlated with some echocardiographic indices in 20 patients chronic renal
      failure (c.r.f.) on conservative treatment (10 women and 10 men, aged 43.6 +/-
      9.8 years). Comparative groups consisted of 10 patients with chronic primary
      glomerulonephritis without arterial hypertension and renal failure (2 women and 8
      men, aged 34.2 +/- 10.5 years), and 10 patients with primary arterial
      hypertension without clinical symptoms of renal disease (1 woman and 9 men, aged
      36.6 +/- 9.5 years). In c.r.f. patients echocardiographic investigations
      disclosed that the left atrial diastolic dimension was within a normal range. The
      right ventricular diastolic dimension (RVDD) was, left ventricular systolic
      (LVDS) and diastolic (LVDD) dimensions and left ventricular end-diastolic volume
      (LVEDV) were slightly increased. The left ventricular ejection fraction (EF) was
      significantly lowered. In c.r.f. patients the left ventricular mass (LVM) was
      increased to approximately 300 g. In c.r.f. patients a significant positive
      correlation was found between number of ventricular extrasystoles registered
      within 24 hrs and RVDD. The investigation disclosed that: 1) in c.r.f. patients
      with arterial hypertension showed ultrasonographic signs of hypertrophic-dilated
      cardiomyopathy with impaired left ventricular ejection fraction; 2) in c.r.f.
      patients incidence and nature of cardiac arrhythmias were independent of LVM,
      LVDD and LVDS; 3) numbers of ventricular extrasystoles registered within 24 hrs
      can increase with the increase in RVDD and the decrease in EF.

PMID- 8146050
TI  - [Actinomycosis as a complication of blood diseases].
AB  - Two cases of actinomycosis in chronic myelogenous leukaemia (CML) and Hodgkin's
      disease (HD) are presented. The first patient with blastic crisis in CML had
      painful infiltration above and beneath the clavicular region, affecting the right
      humeral joint, what required differentiation from neoplastic infiltration.
      Specific infiltration, formation of fistuli and good response to antibiotic
      therapy suggested actinomycosis. Finally actinomycosis was diagnosed by
      microbiological and histopathological examination. The infection with
      actinomycosis in the other patient interfered with early diagnosis of coexistant
      Hodgkin's disease. The histopathologic examination of right cervical lymph nodes
      indicated the chronic inflammatory process. The subsequent histo pathologic
      examination of the axillary lymph node showed Hodgkin's disease, type LD. Culture
      from the exudating wound after lymph node excision was positive for actinomyces.
      Simultaneous treatment with cytostatics and antibiotics resulted in complete
      recovery of patient. In the above reported patients, actinomycosis complicated
      the course of CML and HD. The immune deficiency of the organism in both patients
      facilitated the development of the actinomycosis.

PMID- 8146051
TI  - [Hyperlipidemia and cardiovascular diseases. The report of the Symposium of
      Nutrition and Metabolism section of Polish Internists Association, Warsaw,
      28.05.1993].

PMID- 8146052
TI  - [Diagnosis, pathogenesis and treatment of panic attacks].
AB  - Panic accompanies several diseases both psychological and somatic. It may be
      secondary, i.e. produced by other symptoms and morbid processes. It may also be
      primary--"neurotic". In such cases there are two forms of panic: generalized and
      paroxysmal. Attacks of panic are seen in 1.6-2.9% of women and in 0.4-1.7% of
      men. Main pathogenetic role is played by the psychologic factors (psychical
      trauma precedes the onset of diseases). The role of biological factors is also
      important. It is believed that disorders of the noradrenergic, serotonin-ergic,
      and GABA-ergic transmission may produce the attacks of panic. Psychotherapy is a
      treatment of choice. Pharmacotherapy plays only an adjuvant role. Antidepressants
      (tricyclic of II generation) are most frequently used for this purpose and-
      exceptionally due to possible addiction--benzodiazepines. The highest impact on
      the development of disease has first contact physician attitude. Patient and
      thoughtful listening to the patient, explanation of the complaints and their
      source often produce and improvement, and even complete recovery.

PMID- 8146053
TI  - [Home environment of children with alcoholic parents].

PMID- 8146056
TI  - [Degrees of alcoholic dependency in patient's self evaluation].
AB  - The study involved a group of 33 males with diagnosed alcohol abuse. A degree of
      the disease was determined according to Standard Anamnesis Sheet and Auxilliary
      Alcohol Dependence Questionnaire (Woronowicz's Questionnaire). The patient's
      results were compared with their wives' results in order to determine
      trustworthiness. The goal of this study was to determine the factors influencing
      patient's critical assessment of their disease. The results reveal a relationship
      between patient's assessment and clinical manifestations of their dependence tend
      to underestimate the degree of their disease.

PMID- 8146055
TI  - [Social development and fulfillment of school responsibilities in children of
      alcoholic parents].

PMID- 8146054
TI  - [Evaluation of physical and psychoneurologic development of children with
      alcoholic parents].

PMID- 8146057
TI  - [Diagnosis of type A behavior pattern in patients with somatic risk factors for
      coronary disease].
AB  - Some theorists hypothesize that type A behavior--considered as an important
      coronary risk factor--differentially impacts upon the health of persons with
      varying needs for stimulation. Depending on the stimulation needed and the
      temperament features from which the need derives, a highly stimulating life-style
      either remains within or surpasses the individuals capacity. Heightened trait
      anxiety level is theorized to be the index of the overload in the biological
      system of high-reactive persons of type A. The data collected show that type A
      behaviour considered separately leads to a different evaluation of coronary risk
      from a situation in which temperament features and the anxiety level are taken
      into account. Patients of higher type A were characterized by a higher need for
      stimulation than patients of lower type A. Anxiety levels were the same in both
      groups. Thus, the levels of coronary risk can be evaluated as comparable, despite
      the difference in type A intensity. The diagnosis of the negative impact of type
      A on health is more accurate, if the variables of temperament and personality are
      included.

PMID- 8146058
TI  - [Relationship between pain and panic in mitral valve prolapse syndrome].
AB  - The study aimed at assessing a relationship between pain and panic in the
      echocardiographically confirmed mitral valve prolapse syndrome. Thirty three
      patients, 23 women and 10 men, were included. Mean age was 32 years. Standard
      Pain Perception Questionnaire by Melzack and Ostrowski's Well Being Questionnaire
      were used. During examination all patients were free from pain. Therefore,
      delayed pain effect was assessed. Present pain was evaluated with different
      scale. Significant relationship between pain and panic was shown in the mitral
      valve prolapse syndrome. In retrospective analysis pain was responsible for 16%
      of panic disorders (n = 0.396; p < .02). An effect of the actual pain is less
      pronounced and explain 14% of panic disorders (n = 0.372; p < .02), as the actual
      pain was less intense. There was also contrary relationship, but weaker. Panic
      exerts an effect on pain intensity in 11% (n = 0.330; p < .05). In the system
      pain-panic the former is prevailing in this syndrome. The obtained results
      confirm the value of psychotherapy modifying panic disorders.

PMID- 8146059
TI  - [Psychiatric decision to admit a patient to the hospital].

PMID- 8146060
TI  - [Holter monitoring in diagnosis of syncope].
AB  - Thirty two patient with a history of brief unconsciousness underwent a constant
      ECG monitoring with Holter's technique for 24-72 hours. Syncope was noted in 16
      patients. Cardiac arrhythmia was a cause of unconsciousness in 14 patients
      whereas no such a pathology was seen in the remaining two patients. No syncope
      was seen during ECG monitoring in 16 patients. Loss of consciousness was found in
      the majority of patients monitored for 72 hours. This technique may be valuable
      in the diagnosis of syncope, especially when it appears during ECG monitoring.

PMID- 8146061
TI  - [Depressive disorders in children and adolescents].
AB  - The author presents the results of a 5-7-year research in 99 children and 74
      adolescents suffering from depressive disorders. It was found that the etiology
      of depressive disorders, even at the same group of syndrome-associated diagnosis
      (DSM-III) was various. In this group very often psychogenic disorders, were
      present, and endogenous affective disorders were rare. An existence of atypical
      pictures of some depressive disorders (cyclic anxiety disorders and/or cyclic
      aggressive disorders was shown in the examined patients.

PMID- 8146062
TI  - [Schizophrenia and substance abuse].

PMID- 8146063
TI  - [Maternal age and Down's syndrome (trisomy 21) in light of current knowledge].

PMID- 8146065
TI  - [The place of Janusz Korczak in medical culture].

PMID- 8146064
TI  - [Head injuries and alcohol--social and economic costs].
AB  - The authors tried to calculate the costs due to head trauma in drunkard s
      hospitalized in Lodz. An analysis included: costs of the hospitalization,
      reimbursements, additional costs of the neurological and surgical management, and
      costs Emergency Service (ambulances). It was found that Lodz inhabitants pay
      annually nearly 7 billion Zloty. The authors suggest that actual regulations
      concerning free health care should be modified in case of alcoholics. Such
      patients should bear all costs related to their transport to the hospitals,
      treatment and additional tests.

PMID- 8146067
TI  - Influence of culture media on the morphological differentiation of the PC-3 and
      DU145 prostatic neoplastic cell lines.
AB  - The concept of differentiation of prostate cancer in terms of morphonuclear
      characteristics and population dynamics was investigated on the PC-3 and DU145
      cell lines. A software based on the concept of Voronoi paving was set up in order
      to characterize the structure of these cell lines growing in vitro on
      histological slides. The morphonuclear characteristics were assessed by means of
      the digital cell image analyses of Feulgen-stained nuclei. The in vitro
      "morphonuclear" and "pseudo-tissular" differentiations of the PC-3 and DU145
      cells were described in terms of the use of various culture media, i.e., media
      supplemented with either 10% (F10 medium) or 1% (F1 medium) fetal calf serum and
      with (or without) platelet-derived growth factor and dihydrotestosterone (PA10
      and PA1 media). The present data reveal that the PC-3 cell line would be more
      hormone-sensitive than the DU145 one. Indeed, decreasing the FCS concentration in
      the culture medium while adding DHT and PDGF led to marked modifications to the
      morphonuclear characteristics of the PC-3 cells, but not to the DU145 cells.
      These modifications corresponded to an increase in nuclear size occurring
      concomitantly with chromatin decondensation. In the same way, spectacular
      modifications in terms of medium-induced pseudo-tissular differentiation were
      observed in the PC-3 cell line, but not in the DU145 one. Such modifications
      corresponded to an increase in clone size related to an increase in the mean
      distances between neighboring cell nuclei in a given clone. Thus, according to
      the criteria defined in this study, the PC-3 cell line would seem to maintain a
      higher degree of differentiation than the DU145 cell line.

PMID- 8146068
TI  - Effect of early exposure of flutamide on subsequent growth of transplantable rat
      prostatic tumor (dunning R-3327).
AB  - Rat transplantable prostatic tumors (Dunning R-3327) were treated with flutamide
      before tumors grew palpable, in order to examine the effect of short term
      treatment of antiandrogen for prostatic cancer in latent period on the growth
      after appearance of tumor. Flutamide delayed an appearance of the tumor nodule
      and retarded the growth rate in proportion as treatment began earlier. Flutamide
      also reduced final tumor volume. Flutamide-treated tumors histologically
      consisted of small or dilated glandular structure with an increase in stromal
      area, but androgen receptors were preserved. Flutamide-treated tumor showed slow
      growth with androgen sensitivity when transplanted to intact rats, showing
      prolonged influences of antiandrogen on tumor growth. There was no significant
      difference between flutamide-treated and control groups in weight of accessory
      sex organs and serum androgen or estrogen levels. In conclusion, flutamide
      treatment may retard an appearance of prostatic cancer concomitant in benign
      prostatic hyperplasia.

PMID- 8146066
TI  - Antiandrogens inhibit human androgen receptor-dependent gene transcription
      activation in the human prostate cancer cells LNCaP.
AB  - Human androgen receptor (hAR) is a ligand-dependent transcription factor that
      mediates androgen-induced actions on target tissues. Transfection studies in the
      human prostate cancer cell line LNCaP examine the ability of dihydrotestosterone
      (DHT), hydroxyflutamide (HO-FLU), cyproterone acetate (Cypro.A), and RU 23908-10
      to stimulate or to inhibit the transcription activation of mouse mammary tumor
      virus-bacterial chloramphenicol acetyltransferase (MMTV-CAT). DHT stimulated
      transcription activation of MMTV-CAT gene in LNCaP cells in a dose-dependent
      manner. HO-FLU, Cypro.A, and RU 23908-10, though only partially, also stimulated
      the transcription activation of MMTV-CAT. Despite this, 100- to 1,000-fold molar
      excess of all antiandrogens inhibited the agonistic activity of 10 nM DHT in this
      system. Receptor binding assays confirmed that HO-FLU, Cypro.A, and RU 23908-10
      competed with DHT for AR binding in LNCaP cells. Western blot analysis using AR
      antipeptide antibodies raised in rabbits revealed the presence of two AR protein
      bands in LNCaP cells, following treatment with antiandrogens. Increasing doses of
      HO-FLU stimulated the expression of the 114-kDa AR by 2.5-fold, but did not
      affect the 108-kDa AR. Increasing doses of Cypro.A and RU 23908-10 decreased the
      levels of both the 114-kDa and the 108-kDa AR. Although the exact nature of 108
      kDa and 114-kDa AR in LNCaP cells is still unknown, these data suggest that the
      regulatory actions of each individual antiandrogen on AR expression in LNCaP
      cells may be different.

PMID- 8146069
TI  - Expression of bone morphogenetic protein messenger RNAs by normal rat and human
      prostate and prostate cancer cells.
AB  - Human prostate cancer cells are known to produce several growth regulatory
      factors, including transforming growth factor beta (TGF beta) and heparin-binding
      fibroblast growth factors (FGFs), which may play as-yet-undefined roles in
      prostate gland morphogenesis, as well as in prostate cancer cell behavior.
      Recently, a family of proteins in the extended TGF beta family, the bone
      morphogenetic proteins (BMPs), has been identified which stimulates bone
      formation in vivo, and in which, the proteins are likely involved in a variety of
      morphogenetic processes during embryogenesis. These powerful morphogenetic
      factors are capable of redirecting muscle mesenchyme cells to differentiate along
      the lines of bone tissue. We examined a number of well-characterized rat and
      human prostate cancer cell lines for the expression of BMP 2, 3, 4, and 6
      messenger RNA. Poly(A+)-RNA was isolated from normal human and rat ventral
      prostate, from the rat prostate adenocarcinoma PAIII tumor and cultured cells
      derived from it, and from human prostate cancer cell lines PC-3, LNCaP, and DU
      145. BMP mRNA levels were measured using BMP 2, 3, 4 and Vgr-1 (BMP 6) cDNA
      probes. Both normal and neoplastic prostate tissue expressed these BMP mRNAs,
      although the level of expression varied from tumor to tumor. Normal human
      prostate expressed BMP 4 mRNA predominantly, as did the human prostate cancers PC
      3 and DU-145. PC-3 also expressed BMP 2 mRNA and BMP 3 mRNA in large amounts.
      Normal rat ventral prostate expressed all these BMP mRNAs, but the rat prostate
      adenocarcinoma PAIII expressed predominantly BMP 3 mRNA. The reason that
      different BMPs are expressed in varying amounts by these normal and neoplastic
      cells is unknown. However, if these BMPs are expressed in biologically active
      form, they could be responsible for important effects on normal prostate growth
      and morphogenesis, on neoplastic prostate cell behavior, and could even
      contribute to the capacity of prostatic cancer cells to stimulate new bone
      formation at metastatic tumor sites in bone.

PMID- 8146070
TI  - Dietary and environmental factors affecting skin strength in broiler chickens.
AB  - Two experiments were conducted to evaluate dietary and environmental factors
      involved in skin tensile strength of commercial broilers. In Experiment 1 the
      effect of added dietary fat (4 or 7%), environmental temperature (25 or 20.5 C
      after 21 d), and anticoccidial drug (halofuginone or salinomycin fed
      continuously) were examined factorially using male and female chicks. Skin
      tensile strength was measured at 21, 35, and 40 d of age. Thickness of the dermal
      layers was measured from skin taken at Day 35. In Experiment 2, the effect of
      added dietary fat (0 or 7%), environmental temperature (25 or 18.5 C after 21 d),
      and anticoccidial drug (halofuginone or salinomycin) were examined factorially
      using female chicks. Skin strength and collagen content of the skin were measured
      at 21, 38, and 42 d of age. Skin tensile strength increased with age in both
      experiments, but female skin strength was subject to periodic decline. Males had
      significantly strong skin than females. Levels of added fat or environmental
      temperature did not affect skin strength in either experiment. Continuous feeding
      of halofuginone significantly (P < .0001) decreased skin strength compared with
      that of birds fed salinomycin in both experiments. Halofuginone reduced skin
      strength in females more than males (25 and 9%, respectively). Dermis thickness
      was correspondingly reduced in the birds consuming halofuginone. In Experiment 2,
      soluble collagen contents were reduced at all ages in birds consuming
      halofuginone; insoluble collagen was significantly decreased at 21 d of age.
      Birds with weakened skin exhibited increased incidence of skin tears during
      slaughter in a commercial processing plant (P < or = .0043). These results
      suggest that halofuginone interferes with collagen synthesis, causing decreased
      collagen formation and reduced skin strength. Neither added dietary fat nor
      ambient temperature were involved.

PMID- 8146071
TI  - Effects of the maternal thyroid status on embryo physiology and hatchability of
      commercial turkey eggs.
AB  - Fertile turkey eggs produced by commercial hens fed iodine or triiodothyronine
      were compared with those from hens fed a control diet to observe the effects of
      the maternal thyroid status on the energy budget of turkey eggs. Dietary iodine
      improved hatchability, decreased the number of dead pips, and maintained blood
      glucose concentrations during pipping and hatching with less reliance on hepatic
      gluconeogenesis (as assessed by glucose-6-phosphatase activity) compared with
      controls. Hatchability of eggs from hens fed triiodothyronine was not different
      from that of control hens but was less than those of iodine-fed hens. The data
      suggest that the maternal thyroid function of commercial breeder hens can
      influence hatchability of their eggs and that dietary iodine may be a means to
      improve hatchability of commercial turkey eggs.

PMID- 8146072
TI  - Response of broiler breeder hens to forced molting by hormonal and dietary
      manipulations.
AB  - Experiments were conducted to compare dietary and hormonal techniques for molting
      broiler breeder hens. In the first experiment, production dropped to 5% 3 wk
      after hens were restricted to an intake of one half of their calculated energy
      requirement (FR). Egg production levels of hens given a single i.m. injection of
      the Lupron Depot formulation of leuprolide acetate (LA) in a dose intended to
      provide 10 micrograms/kg BW per d for 30 d dropped to 9.5% whereas production
      dropped to 33% in hens receiving 5 micrograms and was unchanged by 2.5
      micrograms. Postmolting fertility and hatchability of eggs from the FR and the 10
      micrograms LA groups were not different. In the second experiment, postinjection
      egg production, oviduct weight, and uterus weight were depressed, in a dose
      related manner, when hens received 0, 10, or 22 micrograms LA/kg per d. In a
      third experiment, egg production dropped to zero within 2 wk when hens were
      deprived of feed (FD) or deprived of feed and light (FD+LR), whereas it reached
      zero in 4 wk in hens fed only 30 g of wheat shorts per d (FR). Lupron Depot at a
      dose intended to deliver 30 micrograms/kg BW per d, reduced egg production to
      9.5% by the 3rd wk. Twenty-eight weeks postmolting, egg production ranged from 84
      to 98 eggs per hen in the molted groups and 56 eggs per hen in the unmolted
      controls. Fertility ranged from 82.1% in the FD+LR groups to 69.8% in the
      unmolted controls, whereas chick production averaged 36, 50, 59, 60, and 68
      chicks per hen in the unmolted controls and in hens molted by LA, FR, FD, or
      FD+LR, respectively.

PMID- 8146073
TI  - Responses of laying hens to diets containing up to 2% DL-methionine or equimolar
      (2.25%) 2-hydroxy-4-(methylthio)butanoic acid.
AB  - Diets supplemented with up to .6% DL-Met (DLM) or .68% 2-hydroxy-4
      (methylthio)butanoic acid (HMB, Alimet) acidify the urine and reduce the
      incidence of urolithiasis in pullets and laying hens. Excessive acidification
      potentially may reduce eggshell quality and bone mineralization by interfering
      with Ca metabolism and may severely challenge the liver and kidneys, which are
      the primary organs responsible for attenuating metabolic acidosis. To evaluate
      these possibilities, 30-wk-old Single Comb White Leghorn hens in full production
      (five hens per replicate, six replicates per diet treatment) were fed for 30 d a
      15.7% CP corn and soybean meal-based control layer ration alone or supplemented
      with DLM (.5, 1, 1.5, or 2%) or equimolar HMB (.56, 1.13, 1.69, or 2.25%). None
      of the diets caused mortality or gross hepatic or renal damage. Hens fed diets
      supplemented with the highest levels of DLM and HMB exhibited significant
      reductions in feed intake, hen-day egg production, and liver mass and had lower
      plasma concentrations of alanine amino-transferase and isocitrate dehydrogenase
      when compared with hens fed the control diet. Kidney mass was not significantly
      affected by high levels of DLM or HMB, but plasma uric acid was significantly
      higher in hens fed 2% DLM compared with hens fed the control diet. The highest
      levels of DLM and HMB did not significantly alter total plasma Ca or inorganic
      phosphate concentrations, nor were percentage eggshell or femur mineralization
      (femur ash mass:defatted bone mass, femur ash mass:bone volume) significantly
      reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146074
TI  - Requirement of the laying hen for sulfur amino acids.
AB  - Two experiments with individually caged laying hens were conducted to determine
      the requirement for TSAA. In Experiment 1, the corn-soybean basal diet contained
      .48% TSAA to which increasing dose levels of DL-methionine were added providing
      at the highest supplemental level .645% TSAA. The experimental diets were fed for
      12 wk, covering the early stage of laying from 25 to 37 wk of age. In Experiment
      2, a corn-soybean basal diet containing of .51% TSAA was used along with DL
      methionine supplements to determine TSAA requirement during the entire laying
      cycle of 52 wk (25 to 77 wk of age). The highest supplemental level of DL
      methionine in this experiment provided .76% TSAA. The TSAA requirement was found
      to be higher for maximum efficiency of feed utilization than for obtaining
      maximum egg production. Based on feed conversion efficiency and at an egg mass
      yield of 55 g per hen-day, the requirement for TSAA was estimated to be about 740
      mg per hen-day, of which about 440 mg was methionine, throughout a laying period
      of 52 wk. It was calculated that the estimated TSAA requirement was equivalent to
      approximately 660 mg true digestible SAA per hen-day.

PMID- 8146075
TI  - Dietary carnitine did not influence performance and carcass composition of
      broiler chickens and young turkeys fed low- or high-fat diets.
AB  - Two experiments were conducted to determine the influence of supplemental dietary
      carnitine on performance and carcass composition of young turkeys and broiler
      chickens. Experiments 1 and 2 were done with poults to 21 d of age and broilers
      to 45 d of age, respectively. Three dietary concentrations of L-carnitine (0, 50,
      or 100 mg/kg) were fed in a factorial arrangement with two concentrations of
      animal-vegetable fat (A-V fat), 2.25 or 8% in Experiment 1 and 1 or 5% in
      Experiment 2. L-Carnitine did not affect (P > .05) BW gain or feed efficiency in
      either experiment, irrespective of concentration of dietary fat. Similarly,
      proximate composition of 21-d-old poults and 45-d-old broilers was not changed by
      L-carnitine. Increasing levels of fat supplementation improved feed efficiency of
      poults and improved 45-d BW and feed efficiency of broilers. Carcass fat of
      poults and broilers was increased (P < or = .05) by supplemental fat at the
      expense of carcass water and protein.

PMID- 8146076
TI  - Quantitative requirement for cholecalciferol in the absence of ultraviolet light.
AB  - Studies were conducted to determine the basic requirement of the bird for
      cholecalciferol in the absence of ultraviolet light by utilizing filter sleeves
      on fluorescent lights in the room and brooder. In Experiment 1, some pens were
      fitted with filter tubes and some lights were turned off. All the birds received
      a cholecalciferol-deficient diet. Birds with ultraviolet light excluded grew
      slowly, developed rickets (95%), had low plasma calcium, and low bone ash (27%);
      whereas birds exposed to the fluorescent light had normal growth and plasma
      calcium, slightly low bone ash (38%), and some rickets (12%). Experiments 2 and 3
      were conducted to determine the amount of cholecalciferol that must be added to
      the diet under conditions in which ultraviolet light was excluded. In Experiment
      2, the highest level of cholecalciferol fed was 400 ICU/kg. This level was not
      sufficient to permit the chickens to have weight gain or bone ash equal to the
      birds receiving the ultraviolet light. The birds receiving 400 ICU/kg of diet
      also had a 77% incidence of rickets compared with 20% for the birds receiving
      ultraviolet lights. In Experiment 3, when birds received 800 or 1,600 ICU/kg of
      cholecalciferol in the diet, they grew and were comparable to those receiving
      ultraviolet light for the criteria measured.

PMID- 8146077
TI  - Effect of removing trace minerals from the diet of hens laying eggs with heavy or
      light shell weight.
AB  - Hy-Line W36 hens, 48-wk-old, were used to study the effect of removing either
      supplemental Fe, Cu, Zn, Mn, or all of them from the diet of hens laying eggs
      with heavy shell weight (HSW) or light shell weight (LSW). The experiment was
      conducted for 10 wk. Egg production (EP), egg mass (EM), feed consumption (FC),
      feed conversion efficiency (FE, grams feed:gram egg), egg weight (EW), shell
      weight (SW), percentage shell (PS), specific gravity (SG), percentage fertility,
      percentage hatchability of fertile eggs (HF), and percentage hatchability of
      total eggs set (HT) were measured. Removing trace minerals from the diet had no
      significant effect on EP, EM, FC, FE, EW, PS, SG, HF, or HT with either HSW or
      LSW hens. However, removing Mn from the diet significantly reduced SW with HSW
      hens. Diet by shell classes (HSW and LSW) interaction was not significant for any
      variable measured. The HSW hens had significantly higher EW, SW, PS, SG, and EM
      and lower EP, HF, and HT. However, there were no significant differences on FC or
      percentage fertility between the two groups of hens.

PMID- 8146078
TI  - Water-holding properties of thermally preconditioned chicken breast and leg meat.
AB  - A study was conducted to examine the effects of thermal preconditioning on the
      water-holding properties of chicken breast and leg meat. An initial experiment
      was performed by heat shocking (40 to 41 C for 1 h) and euthanatizing broilers at
      3 to 6 wk of age. As seen commercially, heat caused higher drip loss, and the
      majority of this loss for breast (75 to 80%) and leg (90 to 100%) meat occurred
      within 3 d post-mortem. A second study with 6-wk-old broilers tested the
      following treatments: control (25 C), heat shock (40 to 41 C for 1 h),
      preconditioned control (3 consecutive d of exposure to 35 C for 3 h followed by a
      21-h recovery between each exposure), and preconditioned (same as preconditioned
      control with an added heat shock on the final day). Thermal preconditioning did
      not circumvent the water-holding problems associated with heat shock. Meat from
      chickens exposed to heat lost significant amounts of drip during the crucial
      processing period--the first 6 h after death. In general, leg meat had lower drip
      loss and higher held water than breast, but cooked leg meat had lower held water.
      Treatment and meat type were significant (P < .05) in determining drip and cook
      loss. Preconditioned and heat shock breast meat appeared pale, soft, and
      exudative, similar to a condition found in pork. Thermal preconditioning does not
      prevent the loss in water-holding properties associated with heat.

PMID- 8146079
TI  - Effect of halofuginone on broiler skin strength when used in a shuttle
      anticoccidial program.
AB  - Continuous feeding of the anticoccidial halofuginone to broilers is associated
      with reduced skin tensile strength and increased skin tearing during processing.
      The possible mitigating effect of shuttle administration of halofuginone and
      salinomycin to female broilers was evaluated. Halofuginone or salinomycin were
      included in the starter and grower diets in all four possible combinations, with
      anticoccidial omitted from the finisher diets. Starter, grower, and finisher
      diets were fed to broilers through 3, 6, and 7 wk of age, respectively. Skin
      strength of pullets fed a diet based on milo and corn (NW) vs a diet based on
      corn was also compared in a factorial arrangement. Two further treatments were
      also included: 1) halofuginone-only NW diet supplemented with 2,500 ppm ascorbic
      acid from 0 to 7 wk; and 2) NW diet reared on wire floor without anticoccidial
      treatment. Skin tensile strength was determined at 3, 6, and 7 wk of age. Dietary
      composition had no effect upon skin strength or BW of broilers. Addition of
      ascorbic acid to the diet containing halofuginone anticoccidial did not improve
      skin strength. Continuous feeding of halofuginone reduced skin strength whereas
      withholding anticoccidial and continuous feeding of salinomycin resulted in high
      skin strength. When halofuginone was used in shuttle feeding programs with
      salinomycin, there were no differences in skin strength at 7 wk of age compared
      to birds that were continuously treated with salinomycin. These results suggest
      halofuginone may be used in a shuttle program either during the starter or grower
      phase without adverse affect on skin tensile strength at slaughter.

PMID- 8146080
TI  - Increased redness in turkey breast muscle induced by fusarial culture materials.
AB  - Short-term feeding trials with experimentally moldy rice (10% of diet) or corn
      (12.5%) were carried out on turkey poults to screen for toxigenic Fusarium,
      Penicillium, and Aspergillus, which were recovered from corn or commercial turkey
      feed. A major finding was that culture materials of some fusaria increased the
      redness of turkey breast muscle without causing obvious hemorrhages either in the
      musculature or in the internal organs. Corn culture but not rice culture of
      Fusarium moniliforme (M-1325) depressed body weight gains, feed utilization, and
      heart weights (P = .01). The increased redness (reddish discoloration) could lead
      to the depreciation of fresh turkey muscle product.

PMID- 8146081
TI  - In vitro T cell activity in two chicken lines divergently selected for antibody
      response to sheep erythrocytes.
AB  - Four experiments were conducted to determine possible differences in the in vitro
      concanavalin A (ConA) response between two lines selected either for high (H) or
      low (L) antibody response 5 d after intramuscular immunization with SRBC. In all
      four experiments, the cell proliferation after stimulation with ConA was higher,
      although not always significantly so, in the L line than in the H line,
      independently of dose of Con A and source of lymphocytes. It can be concluded
      that selection for anti-SRBC antibody response affected the cellular response in
      chickens. Previously reported results, in other chicken lines selected for
      humoral response to SRBC after intravenous immunization with SRBC, showed an
      opposite line difference in mitogen response. These opposite results point to the
      fact that comparable selection protocols for immunological variables do not
      necessarily have a comparable influence on the diverse components of the immune
      response.

PMID- 8146082
TI  - Evaluation of the humoral immune response to different antigens in Arkansas
      Regressor and Progressor chickens.
AB  - Arkansas Regressor and Progressor chickens were re-evaluated for their immune
      response to different antigens. Chickens received i.v. injection of either SRBC
      (10 birds per line) or Salmonella pullorum (SP; 10 birds per line) at 7 wk of
      age, and sera were collected at 6, 13, and 20 d postimmunization. A third group
      of birds (10 birds per line) received and i.m. injection of GAT emulsion at 7 and
      12 wk of age, and sera were collected at 10 and 14 wk of age. There were
      significant differences between the two lines in their humoral immunity to SRBC,
      SP, and GAT. Such results suggest genetic control of humoral immunity to these
      antigens in these lines. It is unknown whether humoral immunity to these antigens
      is correlated to regression of tumors induced by Rous sarcoma virus.

PMID- 8146083
TI  - Brucella abortus antibody response of white Leghorn chickens selected for high
      and low antibody responsiveness to sheep erythrocytes.
AB  - Three experiments were conducted with lines of chickens selected for high (HA)
      and low (LA) antibody response to sheep erythrocytes to determine their antibody
      responses following primary immunization with Brucella abortus. In Experiment 1,
      HA chicks responded to immunization with a higher total titer than LA chicks at 7
      d postimmunization. At both 5 and 7 d following immunization 2-mercaptoethanol
      resistant (IgG) titers were higher in HA than LA chicks. There also was a
      significant sex effect at 7 d in the first experiment, with males having higher
      total titers than females. In the second experiment, HA chicks had higher total
      titers at 5 d postimmunization than LA chicks, but IgG titers were similar for
      both lines. Total and IgG titers of HA chicks used in Experiment 3 were
      significantly higher than those of LA chicks at 5 and 7 d postimmunization. Both
      HA and LA chicks exhibited divergent antibody responses to B. abortus although
      they had originally been selected for antibody responsiveness to sheep
      erythrocytes.

PMID- 8146084
TI  - Effects of electrolyte and lighting regimen on growth of heat-distressed
      broilers.
AB  - The purpose of this study was to investigate possible interactions between
      photoschedules [23 h light (L):1 h dark (D); 16L:8D] and electrolytes provided by
      KCl and NaCl in the drinking water of broilers grown at elevated temperatures.
      Birds raised on each photoschedule were exposed to 8 h of 23.9 C, 4 h of 23.9 to
      35 C, 4 h of 35 C, and 8 h of 35 to 23.9 C. Photoschedule had no effect on body
      weight gain, feed consumption, or carcass characteristics. Male birds that
      received NaCl gained 10.5% more (P < .05) weight than those receiving no water
      additive. Male birds consumed up to 37% more water (P < .05) and gained up to 21%
      more weight (P < .05) than similarly raised females. There was no effect of
      electrolytes on carcass characteristics.

PMID- 8146085
TI  - Detection of Salmonella enteritidis in feces from poultry using booster
      polymerase chain reaction and oligonucleotide primers specific for all members of
      the genus Salmonella.
AB  - Salmonella enteritidis was identified in feces from hens using the polymerase
      chain reaction (PCR) and oligonucleotide primers specific for all members of the
      genus Salmonella. Feces from specific-pathogen-free Leghorn hens were determined
      to be negative for Salmonella by microbiological culture and by the PCR. Fecal
      samples were inoculated with known numbers of colony-forming units of S.
      enteritidis. The DNA was extracted from fecal samples and amplified by the PCR
      using genus-specific primers. Salmonella were detected in all samples known to be
      positive; the sensitivity of the assay extended to 1 cfu of S. enteritidis/g
      feces. Feces that were not inoculated with Salmonella were negative.
      Microbiological culture was less sensitive than the PCR assay; results of culture
      of feces with less than 10(2) cfu/g were negative. Although S. enteritidis was
      used in this study, the oligonucleotide primers used in this study have been
      previously demonstrated to be genus-specific for Salmonella.

PMID- 8146086
TI  - Actions of lithium on the cyclic AMP signalling system in various regions of the
      brain--possible relations to its psychotropic actions. A study on the adenylate
      cyclase in rat cerebral cortex, corpus striatum and hippocampus.
AB  - It has been estimated that in most industrialized countries 1 person out of every
      1000 in the population is undergoing lithium treatment to stabilize their
      episodic mood disturbances due to manic-depressive illness. Lithium may stabilize
      mood swings by altering the action of certain neurotransmitters at the synaptic
      level in the brain. Recent research suggests that lithium alters
      neurotransmission by affecting neurotransmitter-coupled second messenger systems.
      A major second messenger system is the adenylate cyclase, which generates
      intracellular cAMP from ATP. The adenylate cyclases (type I-IV) are regulated by
      stimulatory and inhibitory receptors, which either stimulate or inhibit the
      adenylate cyclase activity. The stimulatory and inhibitory neurotransmitter
      receptor signals are transferred to the catalytic unit of the adenylate cyclase
      by Gs and Gi, respectively. The activated receptor induces GTP stimulation of the
      heterotrimeric G protein, leading to a dissociation of the protein into the
      active alpha*GTP and the beta gamma complex. The former stimulates the catalytic
      unit of adenylate cyclase. The stimulation is terminated by a GTPase located on
      the alpha subunit that converts GTP to inactive GDP. At present, G proteins are
      known to play a central role in coupling receptors to effector proteins. In
      addition to extracellular regulation due to neurotransmitters, some adenylate
      cyclases (type I, III) are regulated by CaM as a consequence of enhanced
      intracellular concentrations of free Ca2+. The Ca(2+)-dependent stimulation of
      adenylate cyclase by CaM is assumed to occur by a direct effect on the catalytic
      unit. The catalytic units sensitive to Ca(2+)-CaM are also subjected to
      regulation by stimulatory and inhibitory neurotransmitter stimuli. Magnesium is
      essential for adenylate cyclase activity, since MgATP2- is the enzyme substrate.
      Furthermore, one Mg2+ site located on the G protein regulates both the receptor
      agonist affinity and the dissociation of the G protein during the activation
      cycle. A second Mg2+ site on the catalytic unit is responsible for Mg2+
      regulation of the catalytic activity. The present work aimed at investigating the
      mechanisms by which lithium in vitro and after chronic treatment (ex vivo)
      affects adenylate cyclase activities in various regions of the rat brain. Lithium
      in vitro and ex vivo inhibited the selective stimulation of adenylate cyclase by
      Ca(2+)-CaM in the cerebral cortex. Furthermore, lithium in vitro interacted
      directly with the catalytic unit of adenylate cyclase.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8146087
TI  - Organ-specific metastases in melanoma: experimental animal models.
AB  - Metastases from certain primary tumors frequently exhibit specific organ
      preference. Animal models have been developed to induce in a reproducible fashion
      the formation of organ-specific metastases by malignant melanoma cells. Some of
      these models rely on the use of immunodeficient mice, which can support the
      growth of murine as well as human malignant melanomas. Moreover, immunodeficient
      mice, because of their diminished ability to mount an effective immune response,
      allow the expression of malignant properties (e.g., preferential colonization of
      certain organs), which are intrinsic to transplanted melanoma cells. This review
      discusses the relevant factors (and limitations) of some of the animal models
      used to study the in vivo properties of melanoma cells.

PMID- 8146089
TI  - Cytoskeletal architecture of dermal chromatophores of the freshwater teleost
      Oryzias latipes.
AB  - Cytoskeletal construction of dermal chromatophores of Oryzias latipes was studied
      by immunofluorescence microscopy. A microtubule system was most prominent in
      melanophores where a large number of microtubules emanated from the center of the
      cell. Xanthophores had an arrangement basically similar to that of melanophores,
      though the radial pattern became more irregular in the peripheral region where
      intersecting wavy microtubules were quite frequent. Oval-shaped leucophores
      exhibited the least-developed microtubule system, where the limited number of
      microtubules formed a loose basket-like architecture. Intermediate filaments were
      ubiquitously present in all types of chromatophores and were found to be vimentin
      immunoreactive. Examination of doubly-labeled cells indicated that vimentin
      filaments had similar distribution patterns with microtubules. Orderly arranged
      bundles of actin filaments were found only in xanthophores, while in melanophores
      and xanthophores, actin expression was diffuse without displaying a conspicuous
      filamentous organization. Colchicine treatment induced depolymerization of
      microtubules and retraction of dendrites in varying degrees in cells in culture
      and in situ. Melanophores in culture are very sensitive to the treatment while
      xanthophores appeared to be more resistant in respect to the maintenance of cell
      morphology.

PMID- 8146088
TI  - Calcium plays a complex role in the regulation of melanogenesis in murine B16
      melanoma cells.
AB  - To learn more of the role of calcium in the regulation of melanogenesis, we have
      used direct manipulation of medium calcium and pharmacological modulation of
      intracellular calcium to examine the consequences on unstimulated and cyclic AMP
      elevated tyrosinase activity and melanin synthesis and distribution in B16
      melanoma cells. In unstimulated cells, calcium is clearly inhibitory to
      tyrosinase activity. However, in cells stimulated with cAMP-elevating agents the
      requirement for extracellular calcium was changed such that cells required a
      minimum of 0.4-0.6 mmol medium calcium for maximum tyrosinase response to these
      agents. Paradoxically, pharmacologically increasing intracellular calcium in cAMP
      stimulated cells with ionophore inhibited tyrosinase activity, and the calcium
      lowering agent TMB8 and the calcium channel blocker verapamil both stimulated
      tyrosinase activity. When melanin synthesis was measured in cAMP-stimulated
      cells, TMB8 was found to significantly increase the sensitivity and the maximum
      melanogenic response to alpha-MSH, suggesting the presence of at least one level
      of endogenous calcium inhibitory control operative in these cells. In addition,
      TMB8 changed the distribution of melanin between the cell and the medium such
      that, in the presence of alpha-MSH and TMB8, significantly more melanin was
      secreted into the medium. These data suggest that calcium is required for several
      steps in melanogenesis, having an apparently inhibitory effect on pre-tyrosinase
      activity in unstimulated cells, but also showing evidence of a positive role in
      cyclic AMP-stimulated tyrosinase activity, as well as a further possible
      inhibitory role in melanin movement or secretion.

PMID- 8146090
TI  - [Incidence of emotional problems and behavioral difficulties in school and
      correlation with reading and writing disorders: results of a longitudinal study].
AB  - As a part of a longitudinal study on reading development from the 2th to the 8th
      grade teachers ratings about behavior problems of school children and their
      emotional situation were assessed. Problems in motivation and concentration were
      reported most frequent. Comparing children with poor reading and spelling ability
      to children without deficits in reading and spelling, differences could be found.
      Poor readers and spellers showed more dissocial and disturbing classroom
      behavior. Nevertheless, those problems were as persistent as the problems
      reported for children, who did not show any reading and spelling difficulties, or
      increasing in nearly the same ratio over time. This results does not support the
      hypothesis, that behavior problems may occur as a consequence of learning
      difficulties.

PMID- 8146091
TI  - [Focused counseling of mothers of former premature infants].
AB  - Pre-term birth of a baby means a period of considerable emotional stress for
      parents. Even after discharge they remain anxious about caring and future
      developmental problems. A concept for psychological counseling in the first weeks
      after home transition is presented which relates parental fantasies and
      anxiousness with early interactional problems. This approach aims at an
      enhancement of the intuitive parental behaviors for compensation of early risk.

PMID- 8146092
TI  - [Development of children after reproduction-medical treatment of their parents].
AB  - The issue of child development after infertility treatment of the parents deals
      with the impact of technology on the sublime psychic process of establishing the
      pre- and postnatal triad of father, mother and child. The reasons that, in a
      development psychologic and child psychiatric view, lead to the necessity of
      qualitative analysis of the subject are being discussed in this article. In
      addition, the results and findings of existing publications are presented. Last
      not least, the investigation and evaluation of prognostic factors is discussed
      with regard to their importance for the development of parent and child after
      infertility treatment and also for the decision making process when the parents
      are counselled by doctors on the issue of infertility treatment.

PMID- 8146093
TI  - [Psychosomatic consultation and liaison service in pediatrics].
AB  - A short introduction in the history and the definition of the term of
      consultation-liaison-psychiatry resp.-psychosomatics is given. According to a
      cross-section through the younger Anglo-Saxon literature the problems and the
      evaluation of the co-operation between pediatricians and child psychiatrists are
      figured. Considering the tension between these two disciplines potential
      conflicts and their sources are described and interpreted with the intention to
      minimize them. A considerable lack of research in the field of consultation
      liaison psychosomatics in the German speaking area is stated.

PMID- 8146094
TI  - [Relaxation training for children--a review of the literature].
AB  - The results of a literature survey for the use of relaxation methods can be
      summarized to the following essential points: Children are able to learn
      relaxation training--generally better and faster than adults. However, they need
      more external instructions for doing it. The kind of instructions seem not to be
      of so much importance. At least younger children proceed from a more
      heterosuggestive procedure and using of identification figures for the experience
      of relaxation reaction. According to the children's age and the surrounding
      conditions, stories of fantasy can be used. The significance of surrounding
      activities (e.g. games to introduce the training) should not be undervalued for
      the motivation of children and thus for learning and use of the training.
      Generally learning of the training in a group should be preferred to individual
      training. Children should explicitly be trained in transferring of the learned to
      every-day situations.

PMID- 8146095
TI  - [Is reading and writing performance of boys more dependent on quality of
      education than the performance of girls?].
AB  - In a longitudinal study of the reading and spelling development stable
      differences between classes were observed. These differences could be explained
      only in part by differences in the mean of intelligence. In reading and spelling
      skills the girls were about the same level in all classes, whereas the boys in
      the low-achievement classes were much poorer readers and spellers than those in
      the high-achievement classes. The question whether the differences between
      classes in achievement level could be explained as the consequences of
      differences in the quality of reading instruction is discussed as well as the
      additional question whether the larger differences between boys in different
      classes than between girls might be due to an interaction of factors at school
      and outside of school.

PMID- 8146096
TI  - [Diagnostic problems in suspected sexual abuse of handicapped preschool
      children].
AB  - The diagnostic process in four developmentally retarded pre-school girls who, on
      grounds of sexual behaviour inappropriate for their age, were suspected by their
      nursery school teachers of having been sexually abused, is here described as a
      way to understanding the behavioural sympomatology. Suspicion was confirmed only
      in the case of one of the girls. It has been shown that the early development of
      relationship disorders and sensomotory retardation either alone or in connection
      with maternal experience of violence may lead to characteristic forms of
      masturbation, even when sexual abuse has not occurred. The building of a patient
      therapist rapport during the diagnostic process is here even more crucial than in
      the case of non-retarded children. It is only on the basis of the development in
      the child of an improved ability to form relationships that the therapist may
      gain psychological access to the child and thus insight into its traumatising
      experiences.

PMID- 8146097
TI  - [Acceptance of a community child guidance clinic in rural Lower Saxony].

PMID- 8146098
TI  - [Paradoxical interventions: explanation and categorization].
AB  - Paradoxical interventions are of major importance for the systemic family
      therapy. Because paradoxical interventions are widely used and more than 40
      symptoms are treated by them explanations and categorizations of the different
      paradoxical interventions seem to be useful. The double bind hypothesis, but more
      the selection of specific paradoxical interventions dependent on certain client
      characteristics like reactance and perceived freedom of target behavior could
      lead to differential therapeutic effects and improved efficacy of paradoxical
      interventions. The explanation by decontextualization could facilitate the
      integration of paradoxical interventions into the mainstream of psychotherapy. To
      find out whether single paradoxical interventions can be integrated in broader
      theoretical frameworks or not, further discussions are necessary.

PMID- 8146099
TI  - Chemical composition of purslane (Portulaca oleracea).
AB  - Purslane (Portulaca oleracea), grown under greenhouse conditions, was harvested
      at three growth stages and analyzed for total solids, total protein, ash, soluble
      carbohydrate, and fructose/fructane in whole plants, leaves, stems, and roots.
      Significant increases were observed in total solids and protein during plant
      maturation. Leaves had the highest amount of protein in the third growth stage
      (44.25 g/100 g dry matter). Roots showed a decline in protein level as the plant
      aged. Soluble carbohydrate was significantly higher in growth states 1 and 3.
      Significant variation among growth stages was found with regard to total
      phosphorous, calcium, potassium, iron, manganese, and copper. Total phosphorus
      (P) content in leaves was significantly higher than P found in stems and roots.
      Iron (Fe) content varied significantly among growth stages, and roots and leaves
      had the highest Fe content (121.47 and 33.21 mg, respectively). Significant
      accumulation of manganese (Mn) was found in different growth stages. Leaves and
      roots had significantly higher Mn content than stems.

PMID- 8146101
TI  - Evaluation of the effect of processing techniques on the nutrient and
      antinutrient contents of pearl millet (Pennisetum glaucum) seeds.
AB  - This work was undertaken to evaluate the effect of soaking, sprouting, cooking
      and fermentation or their combinations on the nutrient and antinutrient contents
      of pearl millet seeds. Standard assay procedures were adopted to determine both
      the nutrient and the antinutrient concentrations of the products. The synergistic
      effect of cooking and fermentation improved the nutrient quality. The
      antinutrients were reduced to safe levels to a greater extent than did any of the
      other processing techniques or their combinations employed.

PMID- 8146100
TI  - Protein quality traits of vegetable and field peas: varietal differences.
AB  - Four high yielding varieties of field (Rachna and RFP4) and vegetable peas
      (Bonnivielle and Arkal) were studied for their protein quality. Crude protein and
      true protein content of all four pea varieties varied from 19.5 to 20.6 percent
      and 18.7 to 19.8 percent, respectively. Non protein nitrogen formed only 3.94 to
      4.84 percent of total nitrogen. Globulins were the major fractions followed by
      albumins and glutelins. All the four varieties of peas had similar methionine and
      tryptophan content. Lysine content of four pea varieties ranged from 7.56 to 9.65
      g per 16 g of N. Cooking brought about an increase in in vitro protein
      digestibility of peas by 10 percent. The sodium dodecyl polyacrylamide gel
      electrophoresis of total protein revealed the presence of 22-25 bands with some
      difference in banding pattern of all four varieties. Some differences were
      observed in banding patterns of globulin and albumin of all four varieties,
      suggesting that composition of protein of pea varieties differed.

PMID- 8146102
TI  - Some factors controlling carotene destruction by chloroplasts in vitro.
AB  - Loss of beta carotene from moist leaf protein stored with a preservative, is
      closely simulated by the destruction of beta carotene by acetone extracted
      chloroplasts (stroma) suspended in acetone containing 30% water. During this
      exposure, stroma lose destructive ability, but it is restored by mercaptoacetate
      and other reducing agents. Stroma can therefore be used repeatedly. This
      catalytic process is activated by removing intrinsic inhibitors, predominantly
      calcium, by extraction at pHs less than 4, or by alum. The objective is to find
      inhibitors which would be acceptable in a food. That restricts choice. Citrate,
      tartarate and phosphate are among the more attractive possibilities.

PMID- 8146103
TI  - Significance for humans of the nutrient contents of the dry fruit of Tetrapleura
      tetraptera.
AB  - The nutritional quality of the dry fruit of Tetrapleura tetraptera, a tropical
      deciduous forest tree with characteristic fruits, used as a spice, was assessed.
      The fruit shell, fruit pulp and seed contained varying amounts of nutrients such
      as protein, lipids and minerals, which were comparable and some were even higher
      than popular spices such as red pepper, onion, curry and ginger. The crude fibre
      content of the fruit shell was noteworthy and can be considered a good source of
      this nutritional factor. The distribution of crude lipids which indicated the
      location of the aroma of the spice, would enhance the processing of the fruit and
      improve its use.

PMID- 8146104
TI  - Hypocholesterolemic effect of blue-green alga, ishikurage (Nostoc commune) in
      rats fed atherogenic diet.
AB  - Blue-green alga, Nostoc commune is rich in dietary fiber. To examine the
      hypocholesterolemic effect, the alga or the dietary fibers were given to the rats
      fed cholesterol diet. Serum cholesterol elevation was significantly depressed in
      those rats. Cholesterol increased in the liver of rats given the alga and the
      fiber. The content of fecal cholesterol and bile acid unchanged. Of the dietary
      fibers, oxalate-oxalic acid soluble substance (OOSS) found abundant in the alga
      was most effective in lowering cholesterol in the serum. It seems to depress the
      elevation of LDL-cholesterol. The mechanism of hypocholesterolemic effect by OOSS
      remains to be unclear. This study indicated that Nostoc commune is expected to be
      a new dietary fiber source of possible importance in human nutrition.

PMID- 8146105
TI  - Nitrate and vitamin C from fruits and vegetables: impact of intake variations on
      nitrate and nitrite excretions of humans.
AB  - The objective of the study was to determine nitrate + nitrite excretions of human
      subjects fed variable amounts of nitrates and nitrites and vitamin C from fruits
      and vegetables. During four, randomly-arranged experimental periods of seven days
      each, the 12 apparently healthy, adult human subjects consumed laboratory
      controlled, constant, diets which were systematically varied in kinds of fruits
      and vegetable to provide the four following variations: 414 mg nitrate + nitrite
      and 23 mg vitamin C, 412 mg nitrate + nitrite and 177 mg vitamin C, 23 mg nitrate
      + nitrite and 39 mg vitamin C, and 21 mg nitrate + nitrite and 193 mg vitamin C
      per subject per day, respectively. Subjects made complete collections of urine
      and stools throughout the study. Regardless of type of experimental diet fed, no
      nitrates and nitrites were detected in the feces. Urinary excretion of nitrate +
      nitrite was significantly greater at the higher levels of nitrate + nitrite
      intake than at the lower intake levels. Increased intake of vitamin C at either
      level of nitrate + nitrite intake resulted in apparent decreased urinary
      excretions of nitrite + nitrate.

PMID- 8146106
TI  - Preparation and fermentation of rice-defatted soy flour blends: effect on
      protein, fat and ash content.
AB  - Rice-defatted soy flour blends prepared in three proportions viz. 40:60, 50:50
      and 60:40 were fermented with buttermilk at 25, 30 and 35 degrees C for 12, 18
      and 24 h. Fermentation of these blends lowered the pH and raised the titratable
      acidity, maximum drop in pH and rise in titratable acidity being observed at 35
      degrees C for 24 h. The fermentation either decreased or did not change the
      protein content of cereal-legume blends. Fat as well as ash content remained
      unaltered irrespective of temperature and time period of fermentation.

PMID- 8146107
TI  - Resistant starch content of Indian foods.
AB  - Resistant starch (RS) was determined in a few selected cereals, legumes and
      vegetables after processing. Higher RS contents were observed in foods subjected
      to dry heat treatment compared to wet processed ones. Among the foods studied,
      sorghum, green gram dhal, and green plantain showed relatively higher RS content.
      Based on the RS content thus determined in individual foods and the known
      composition of the Indian diet, RS content of Indian diets were computed.

PMID- 8146108
TI  - [Proteolysis of collagen by several species of micromycetes and spore-forming
      bacteria].
AB  - The capability of lysing collagen was studied in 4 species of spore-forming
      bacteria of the genus Bacillus and 9 species of micromycetes of the genera
      Aspergillus, Penicillium, Cladosporium, and Alternaria. A specific medium was
      developed for determining the degree of collagen proteolysis. The spore-forming
      bacteria possessed the higher index of collagen lysis as compared to
      micromycetes. The maximum value of the lysis index was 4 times higher in B.
      licheniformis than in C. herbarum. The latter showed the highest degree of
      collagen proteolysis among the micromycetes studied. The pH optima of collagen
      proteolysis were determined for 5 species of Aspergillus and Penicillium fungi.
      It is shown that a submerged culture of A. chrysogenum used fragments of the
      Achilles tendon as a sole source of carbon. The specific proteolytic activity of
      the collagen-containing medium was 0.8 units of proteinase activity.min.mg
      protein on the 7th day of cultivation.

PMID- 8146109
TI  - [The effect of amino acids and polypeptides on the biomass autolysis process of
      Saccharomyces cerevisiae].
AB  - The inhibitory effect of amino acids on the protease activity of brewer's yeasts
      has been studied. It is shown that amino acids and peptides formed in the course
      of autolysis of brewer's yeasts inhibited the rate of this process. To eliminate
      the inhibitory effect, some exogenous proteases with different substrate
      specificity can be used.

PMID- 8146110
TI  - [Rational organization of the technological processes of hydrolyzing whey lactose
      in the presence of a heterogeneous fiber biocatalyzer].
AB  - We have studied lactose hydrolysis in whey in the presence of a fibrous
      biocatalyst containing immobilized beta-galactosidase in a continuous-flow column
      reactor, and in a reactor unit with substrate recycling in batch and continuous
      regimes. The comparative study of the efficiency of the reactors allowed us to
      recommend the reactor unit with substrate recycling for lactose hydrolysis in
      whey in the batch regime, since it provides both satisfactory hydrodynamic
      stability and high productivity.

PMID- 8146111
TI  - [Microbiological aspects of fermenting chicken manure at various temperatures].
AB  - Mesophilic and thermophilic groups of methanogenic bacteria were found in
      untreated fowl manure. The thermophilic anaerobic fermentation of fowl manure
      leads to the development of both individual methanogens utilizing only some of
      the methane precursors, and syntrophic associations that are also able to utilize
      complex substrates. The selection of methanogenic bacteria during fowl manure
      anaerobic fermentation results in accumulation of thermophilic forms utilizing
      acetate and propionate.

PMID- 8146112
TI  - [Tn5-mutagenesis of the styrene-degrading strain Pseudomonas sp. Y2. Analysis of
      transformation products and DNA-scopy of the mutants obtained].
AB  - The bacterium Pseudomonas sp. Y2 using styrene as a sole source of carbon and
      energy was subjected to transposon Tn5(Kmr) mutagenesis. The mutants were divided
      into three classes by the ability to grow on styrene, 2-phenylethanol, and
      phenylacetate. It is shown that 2-phenylethanol is not an obligate metabolite of
      styrene transformation. This allows the conclusion that in Pseudomonas sp. Y2
      styrene can be degraded via consistent oxidation of the side chain by two
      pathways. For the comparison of strains/mutants and determination of genetic
      markers, DNA-fingerprinting of total DNA was carried out using electrophoresis of
      restriction fragments and blot-hybridization with different 32P-DNA-probes.

PMID- 8146113
TI  - [A comparative study of the effect of inhibitors of microbial origin on different
      alpha-glucosidases].
AB  - The action of a new alpha-glucosidase inhibitor from Streptomyces sp. and
      Acarbose on alpha-glucosidases of various origins has been studied. Differences
      in specificity, efficiency, nature and type of inhibition of microbial
      glucosidases and some enzymes of the small intestine mucosa by the biologically
      active substances studied were revealed. At certain concentrations these
      inhibitors can be substrates for some intestinal glucosidases. It is suggested
      that the inhibitor from Streptomyces sp. (in combination with a diet) can be used
      for regulation of some disturbances in carbohydrate metabolism.

PMID- 8146114
TI  - [Interaction of Bacillus intermedius 7P ribonuclease with ligand-free serum
      albumin].
AB  - The efficiency of the binding of RNase 7P molecules to albumin on cocondensation
      with the aim of producing the prolonged action forms of the enzyme can be
      increased by using ligand-free human serum albumin (LFHSA). The CD method showed
      that LFHSA underwent changes of the cooperative character under the action of
      acid and urea. On potentiometric titration the number of titrated groups of LFHSA
      decreased with time. The GPC method demonstrated the RNase bound more efficiently
      to freshly dissolved LFHSA. In this case part of the enzymic activity was
      manifested only after proteolysis of the albumin carrier. Cocondensation with the
      aid of glutaraldehyde resulted in the formation of LFHSA-RNase conjugates
      composed of 1-2 moles of human serum albumin and 1-6 moles of RNase. More than
      50% of transferase activity retained in the blood plasma for 2-3 days after
      intravenous injection of the conjugates with a molecular weight of 70-80 kD to
      rabbits.

PMID- 8146115
TI  - Discovery of beta-carboline ligands for benzodiazepine receptors.

PMID- 8146116
TI  - Molecular biology of gamma-aminobutyric acid type A/benzodiazepine receptors.

PMID- 8146117
TI  - Immunohistochemical mapping of gamma-aminobutyric acid type-A receptor alpha
      subunits in rat central nervous system.

PMID- 8146118
TI  - Beta-carboline-3-carboxylic acid ethyl ester: a lead for new psychotropic drugs.

PMID- 8146119
TI  - Alpha helix capping in synthetic model peptides by reciprocal side chain-main
      chain interactions: evidence for an N terminal "capping box".
AB  - A significant fraction of the amino acids in proteins are alpha helical in
      conformation. Alpha helices in globular proteins are short, with an average
      length of about twelve residues, so that residues at the ends of helices make up
      an important fraction of all helical residues. In the middle of a helix, H-bonds
      connect the NH and CO groups of each residue to partners four residues along the
      chain. At the ends of a helix, the H-bond potential of the main chain remains
      unfulfilled, and helix capping interactions involving bonds from polar side
      chains to the NH or CO of the backbone have been proposed and detected. In a
      study of synthetic helical peptides, we have found that the sequence Ser-Glu-Asp
      Glu stabilizes the alpha helix in a series of helical peptides with consensus
      sequences. Following the report by Harper and Rose, which identifies SerXaaXaaGlu
      as a member of a class of common motifs at the N termini of alpha helices in
      proteins that they refer to as "capping boxes," we have reexamined the side chain
      main chain interactions in a variant sequence using 1H NMR, and find that the
      postulated reciprocal side chain-backbone bonding between the first Ser and last
      Glu side chains and their peptide NH partners can be resolved. Deletion of two
      residues N terminal to the Ser-Glu-Asp-Glu sequence in these peptides has no
      effect on the initiation of helical structure, as defined by two-dimensional (2D)
      NMR experiments on this variant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146120
TI  - An evaluation of implicit and explicit solvent model systems for the molecular
      dynamics simulation of bacteriophage T4 lysozyme.
AB  - In this report we examine several solvent models for use in molecular dynamics
      simulations of protein molecules with the Discover program from Biosym
      Technologies. Our goal was to find a solvent system which strikes a reasonable
      balance among theoretical rigor, computational efficiency, and experimental
      reality. We chose phage T4 lysozyme as our model protein and analyzed 14
      simulations using different solvent models. We tested both implicit and explicit
      solvent models using either a linear distance-dependent dielectric or a constant
      dielectric. Use of a linear distance-dependent dielectric with implicit solvent
      significantly diminished atomic fluctuations in the protein and kept the protein
      close to the starting crystal structure. In systems using a constant dielectric
      and explicit solvent, atomic fluctuations were much greater and the protein was
      able to sample a larger portion of conformational space. A series of nonbonded
      cutoff distances (9.0, 11.5, 15.0, 20.0 A) using both abrupt and smooth
      truncation of the nonbonded cutoff distances were tested. The method of dual
      cutoffs was also tested. We found that a minimum nonbonded cutoff distance of
      15.0 A was needed in order to properly couple solvent and solute. Distances
      shorter than 15.0 A resulted in a significant temperature gradient between the
      solvent and solute. In all trajectories using the proprietary Discover switching
      function, we found significant denaturation in the protein backbone; we were able
      to run successful trajectories only in those simulations that used no switching
      function. We were able to significantly reduce the computational burden by using
      dual cutoffs and still calculate a quality trajectory. In this method, we found
      that an outer cutoff distance of 15.0 A and an inner cutoff distance of 11.5
      worked well. While a 10 A shell of explicit water yielded the best results, a 6 A
      shell of water yielded satisfactory results with nearly a 40% reduction in
      computational cost.

PMID- 8146121
TI  - Collective motions in proteins investigated by X-ray diffuse scattering.
AB  - We have developed theoretical models for analysis of X-ray diffuse scattering
      from protein crystals. A series of models are proposed to be used for
      experimental data with different degrees of precision. First, we propose the
      normal mode model, where conformational dynamics of a protein is assumed to occur
      mostly in a limited conformational subspace spanned by a small number of low
      frequency normal modes in the protein. When high precision data are available,
      variances and covariances of the normal mode variables can be determined from
      experimental data using this model. For experimental data with lower degrees of
      precision, we introduce a series of simpler models. These models express the
      covariance matrix using relatively simple empirical correlation functions by
      assuming the correlation between a pair of atoms to be isotropic. As an
      application of these simpler models, we calculate diffuse-scattering patterns
      from a human lysozyme crystal to examine how each adjustable parameter in the
      models affects general features of the resulting patterns. The results of the
      calculation are summarized as follows. (1) The higher order scattering makes a
      significant contribution at high resolutions. (2) The resulting simulated
      patterns are sensitive to changes in correlation lengths of about 1 A, as well as
      to changes of the functional form of the correlation function. (3) But only the
      "average" value of the intra- and intermolecular correlation lengths seems to
      determine the gross features of the pattern. (4) The effect of the atom-dependent
      amplitude of fluctuations is difficult to observe.

PMID- 8146122
TI  - Entropy in biological binding processes: estimation of translational entropy
      loss.
AB  - The loss of translational degrees of freedom makes an important, unfavorable
      contribution to the free energy of binding. Examination of experimental values
      suggest that calculation of this entropy using the Sackur-Tetrode equation
      produces largely overestimated values. Better agreement is obtained using the
      cratic entropy. Theoretical considerations suggest that the volumes available for
      the movement of a ligand in solution and in a complex are rather similar,
      suggesting also that the cratic entropy provides the best estimate of the loss of
      translational entropy.

PMID- 8146123
TI  - Magnetic resonance studies of the binding of oligonucleotide substrates to
      mutants of staphylococcal nuclease.
AB  - By a combination of NMR docking and model building, the substrate binding site on
      staphylococcal nuclease was found to accommodate a trinucleotide and to consist
      of three subsites, each interacting with a single nucleotidyl unit of DNA.
      Binding of the essential Ca2+ activator and substrate cleavage occur between
      subsites 1 and 2. Hence, catalytically productive binding would span subsites 1
      and 2 while nonproductive binding would span subsites 2 and 3. Lys-49 is near
      subsite 1, and Lys-84 and Tyr-115 interact with substrates at subsite 3 [Weber,
      D.J., Gittis, A.G., Mullen, G.P., Abeygunawardana, C., Lattman, E.E., Mildvan,
      A.S. Proteins 13:275-287, 1992]. The proposed locations of these subsites were
      independently tested by the effects of the K49A, K84A, and Y115A mutations of
      staphylococcal nuclease on the binding of Mn2+, Ca2+, and the dinucleotide and
      trinucleotide substrates, 5'-pdTdA, dTdA, and dTdAdG. These three mutants have
      previously been shown to be fully active and to have CD and 2D NMR spectra very
      similar to those of the wild-type enzyme (Chuang, W.-J., Weber, D.J., Gittis,
      A.G., Mildvan, A.S. Proteins 17:36-48, 1993). All three mutant enzymes and their
      pdTdA and dTdA complexes (but not their dTdAdG complex) bind Mn2+ and Ca2+ more
      weakly than the wild-type enzyme by factors ranging from 2 to 11. The presence of
      a terminal phosphate as in 5'-pdTdA raises the affinity of the substrate for
      staphylococcal nuclease and its three mutants by two orders of magnitude and for
      the corresponding enzyme-metal complexes by three to four orders of magnitude,
      suggesting that the terminal phosphate is coordinated by the enzyme-bound
      divalent cation. Such complexation would result in the nonproductive binding of
      5'-pdTdA at subsites 2 and 3. Accordingly, the K84A and Y115A mutations
      significantly weaken the binding of 5'-pdTdA and its metal to staphylococcal
      nuclease by factors of 2.2 to 37.8, while the K49A mutation has much smaller or
      no effect. Such nonproductive binding explains the low activity of staphylococcal
      nuclease with small substrates, especially those with a terminal phosphate.
      Similarly, the K84A and Y115A mutations weaken the binding of dTdA and its metal
      complexes to the enzyme by factors of 3.4 to 13.1 while the K49A mutation has
      smaller effects indicating significant nonproductive binding of dTdA. The
      trinucleotide dTdAdG binds more tightly to wild-type and mutant staphylococcal
      nuclease and to its metal complexes than does the dinucleotide dTdA by factors of
      2.4 to 12.2, reflecting the occupancy of an additional subsite.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8146124
TI  - Homologous modeling of the lysosomal protective protein/carboxypeptidase L:
      structural and functional implications of mutations identified in
      galactosialidosis patients.
AB  - The deficiency of the lysosomal protective protein/carboxypeptidase L (CARB L)
      causes the lysosomal storage disorder, galactosialidosis, characterized by
      neuraminidase and beta-galactosidase deficiencies in patients' cells. The three
      enzymes form a complex inside the lysosome, and the neuraminidase and beta
      galactosidase deficiencies are secondary to CARB L deficiency. Sequence
      similarity and common enzymological properties suggest that the protomeric
      tertiary structure of CARB L is conserved within a family of serine
      carboxypeptidases which includes the yeast carboxypeptidase Y, killer expression
      I gene product and several plant carboxypeptidases. We used this homology to
      build a model of the CARB L structure based on the recently published X-ray
      atomic coordinates of the wheat carboxypeptidase II (CPDW-II) which shares 32%
      primary structure identity with CARB L. Small insertions and deletions were
      accommodated into the model structure by energy minimization using the DREIDING
      II force field. The C alpha atomic coordinates of the final CARB L model have a
      RMS shift of 1.01 A compared to the corresponding conserved residues in the CPDW
      II template structure. The correct orientation of the homologous catalytic triad
      residues Ser150, His429 and Asp392, the potential energy calculations and the
      distribution of hydrophobic and hydrophillic residues in the structure all
      support the validity of the CARB L model. Most missense mutations identified in
      galactosialidosis patients were located in secondary structural elements except
      for the Tyr211-->Asn mutation which is in a loop. The other mutant residues have
      their side chains deeply buried in the central beta-sheet of the model structure
      except for the Phe412-->Val mutation which is located in the dimer interface. The
      predicted effects of specific mutations on CARB L structural stability correlates
      well with recently published transient expression studies of mutant CARB L
      (Shimmoto, M. et al., J. Clin. Invest., 91:2393-2399, 1993).

PMID- 8146125
TI  - Molecular surface representations by sparse critical points.
AB  - We have defined a molecular surface representation that describes precisely and
      concisely the complete molecular surface. The representation consists of a
      limited number of critical points disposed at key locations over the surface.
      These points adequately represent the shape and the important characteristics of
      the surface, despite the fact that they are modest in number. We expect the
      representation to be useful in areas such as molecular recognition and
      visualization. In particular, using this representation, we are able to achieve
      accurate and efficient protein-protein and protein-small molecule docking.

PMID- 8146127
TI  - Working parents: the impact of day care and breast-feeding on cytomegalovirus
      infections in offspring.
AB  - The increase in the popularity of breast feeding and utilization of child care
      arrangements are having a major effect on the epidemiology of cytomegalovirus
      infections. The impact is greater for women of upper socioeconomic background who
      send their toddlers to day-care centers and for day-care workers. If primary
      cytomegalovirus infections occur during pregnancy it is logical to anticipate
      more cases of severe congenital infections.

PMID- 8146126
TI  - Lyme disease: a growing threat to urban populations.
AB  - Lyme disease or Lyme borreliosis, which is caused by three groups of the
      spirochete Borrelia burgdorferi, is transmitted in North America, Europe, and
      Asia by ticks of the Ixodes ricinus complex. The primary areas around the world
      that are now affected by Lyme disease are near the terminal moraine of the
      glaciers 15,000 years ago. The emergence of Lyme disease in the United States in
      this century is thought to have occurred because of ecological conditions
      favorable for deer. From 1982 through 1991, 40,195 cases occurring in 47 states
      were reported to the Centers for Disease Control, but enzootic cycles of B.
      burgdorferi have been identified in only 19 states. During the last several
      decades, the disease has spread to new areas and has caused focal outbreaks,
      including locations near Boston, New York, and Philadelphia. Lyme disease is like
      syphilis in its multisystem involvement, occurrence in stages, and mimicry of
      other diseases. Diagnosis of late neurologic abnormalities of the disorder has
      created the most difficulty. A recent phenomenon is that a number of poorly
      understood conditions, such as chronic fatigue syndrome or fibromyalgia, are
      misdiagnosed as "chronic Lyme disease." Part of the reason for misdiagnosis is
      due to problems associated with diagnostic tests. The various manifestations of
      Lyme disease can usually be treated successfully with oral doxycycline or
      amoxicillin, except for objective neurologic manifestations, which seem to
      require intravenous therapy. Vector control of thick-borne diseases has been
      difficult and, therefore, reduction of the risk of infection has been limited
      primarily to personal protection measures.

PMID- 8146128
TI  - Changes in human ecology and behavior in relation to the emergence of diarrheal
      diseases, including cholera.
AB  - Human populations throughout the world can be found in diverse conditions. A
      proportion of the population of developing countries lives in deprived conditions
      characterized by ramshackle housing, lack of piped water and sanitation, and
      widespread fecal contamination of the environment. Enteric infections,
      particularly due to bacterial pathogenes, are readily transmitted under these
      circumstances. In contrast, the majority of inhabitants of industrialized
      countries live in a sanitary environment that generally discourages the
      transmission of enteric pathogenes, particularly bacteria. In both these ecologic
      niches, changes in human ecology and behavior are leading to the emergence of
      certain enteric infections. Relevant factors in developing areas include
      urbanization (leading to periurban slums), diminished breastfeeding, and
      political upheaval that results in population migrations. In industrialized
      areas, large-scale food production (e.g., enormous poultry farms), distribution,
      and retailing (e.g., fast-food chains) create opportunities where widespread and
      extensive outbreaks of food-borne enteric infection can ensue if a breakdown in
      food hygiene occurs.

PMID- 8146129
TI  - Dengue: the risk to developed and developing countries.
AB  - Dengue viruses are members of the Flaviviridae, transmitted principally in a
      cycle involving humans and mosquito vectors. In the last 20 years the incidence
      of dengue fever epidemics has increased and hyperendemic transmission has been
      established over a geographically expanding area. A severe form, dengue
      hemorrhagic fever (DHF), is an immunopathologic disease occurring in persons who
      experience sequential dengue infections. The risk of sequential infections, and
      consequently the incidence of DHF, has risen dramatically, first in Asia and now
      in the Americas. At the root of the emergence of dengue as a major health problem
      are changes in human demography and behavior, leading to unchecked populations of
      and increased exposure to the principal domestic mosquito vector, Aedes aegypti.
      Virus-specified factors also influence the epidemiology of dengue. Speculations
      on future events in the epidemiology, evolution, and biological expression of
      dengue are presented.

PMID- 8146130
TI  - Hepatitis viruses: changing patterns of human disease.
AB  - Viral hepatitis is a disease of antiquity, but evidence for more than one
      etiologic agent has been recognized only since the 1940s, when two viruses
      (hepatitis A virus and hepatitis B virus) were thought to account for all
      disease. In the past 20 years, three additional hepatitis agents (hepatitis C
      virus, hepatitis D virus, and hepatitis E virus) have been discovered, and there
      is evidence for at least one additional virus. Each of the five recognized
      hepatitis viruses belongs to a different virus family, and each has a unique
      epidemiology. The medical impact of these viruses on society has been strongly
      influenced by changes in human ecology. This has resulted in some cases in
      diminished disease and in others in increases in the incidence of disease.

PMID- 8146131
TI  - Population migration and the spread of types 1 and 2 human immunodeficiency
      viruses.
AB  - Over 14 million people are estimated to be infected with the human
      immunodeficiency viruses (HIV), with nearly three-fourths of the infected persons
      residing in developing countries. One factor responsible for dissemination of
      both HIV-1 and HIV-2 worldwide was the intense migration of individuals, from
      rural to urban centers with subsequent return migration and internationally due
      to civil wars, tourism, business purposes, and the drug trade. In sub-Saharan
      Africa, between 1960 and 1980, urban centers with more than 500,000 inhabitants
      increased from 3 to 28, and more than 75 military coups occurred in 30 countries.
      The result was a massive migration of rural inhabitants to urban centers
      concomitant with the spread of HIV-1 to large population centers. With the
      associated demographic, economic, and social changes, an epidemic of sexually
      transmitted diseases and HIV-1 was ignited. Migratory patterns were also
      responsible for the spread of endemic HIV-2 to neighboring West African countries
      and eventually to Europe, the Americans, and India. Although Southeast Asia was
      the last region in which HIV-1 was introduced, it has the greatest potential for
      rapid spread due to population density and inherent risk behaviors. Thus, the
      migration of poor, rural, and young sexually active individuals to urban centers
      coupled with large international movements of HIV-infected individuals played a
      prominent role in the dissemination of HIV globally. The economic recession has
      aggravated the transmission of HIV by directly increasing the population at risk
      through increased urban migration, disruption of rural families and cultural
      values, poverty, and prostitution and indirectly through a decrease in health
      care provision. Consequently, social and economic reform as well as sexual
      behavior education need to be intensified if HIV transmission is to be
      controlled.

PMID- 8146132
TI  - Impact of malaria on genetic polymorphism and genetic diseases in Africans and
      African Americans.
AB  - The high mortality from malaria in sub-Sahara Africa selected multiple genes that
      give the population a selective advantage. Identification of the genetic basis
      for resistance may suggest unusual approaches to development of malarial vaccines
      and antimalarial drugs. Some of these genes may be deleterious, although of
      selective advantage within the African setting, and need to be identified for
      counseling for disease prevention.

PMID- 8146134
TI  - Evolution of drug-resistant tuberculosis: a tale of two species.
AB  - The history of the disease tuberculosis is briefly discussed. Now human societal
      failures have potentiated the evolution of drug-resistant strains of the tubercle
      bacillus in the United States and around the world. Until recently, this
      evolutionary change largely posed a threat to the health and survival of the
      individual in whom inadequate therapy promoted the drug resistance. However, the
      human immunodeficiency virus epidemic threatens to promote wholesale transmission
      of multidrug-resistant tuberculosis with the potential for immense morbidity and
      mortality. Reinforced treatment and control programs for tuberculosis are vital.

PMID- 8146133
TI  - Hospital-acquired infections: diseases with increasingly limited therapies.
AB  - About 5% of patients admitted to acute-care hospitals acquire nosocomial
      infections. A variety of factors contribute: increasing age of patients;
      availability, for treatment of formerly untreatable diseases, of extensive
      surgical and intensive medical therapies; and frequent use of antimicrobial drugs
      capable of selecting a resistant microbial flora. Nosocomial infections due to
      resistant organisms have been a problem ever since infections due to
      penicillinase-producing Staphylococcus aureus were noted within a few years of
      the introduction of penicillin. By the 1960s aerobic Gram-negative bacilli had
      assumed increasing importance as nosocomial pathogens, and many strains were
      resistant to available antimicrobials. During the 1980s the principal organisms
      causing nosocomial bloodstream infections were coagulase-negative staphylococci,
      aerobic Gram-negative bacilli, S. aureus, Candida spp., and Enterococcus spp.
      Coagulase-negative staphylococci and S. aureus are often methicillin-resistant,
      requiring parenteral use of vancomycin. Prevalence of vancomycin resistance among
      enterococcal isolates from patients in intensive care units has increased, likely
      due to increased use of this drug. Plasmid-mediated gentamicin resistance in up
      to 50% of enterococcal isolates, along with enhanced penicillin resistance in
      some strains, leaves few therapeutic options. The emergence of Enterobacteriaceae
      with chromosomal or plasmid-encoded extended spectrum beta-lactamases presents a
      world-wide problem of resistance to third generation cephalosporins. Control of
      these infections rests on (i) monitoring infections with such resistant organisms
      in an ongoing fashion, (ii) prompt institution of barrier precautions when
      infected or colonized patients are identified, and (iii) appropriate use of
      antimicrobials through implementation of antibiotic control programs.

PMID- 8146135
TI  - Effect of changes in human ecology and behavior on patterns of sexually
      transmitted diseases, including human immunodeficiency virus infection.
AB  - The last 20 years have witnessed six striking changes in patterns of sexually
      transmitted diseases (STDs): emergence of new STD organisms and etiologies,
      reemergence of old STDs, shifts in the populations in which STDs are
      concentrated, shifts in the etiological spectra of STD syndromes, alterations in
      the incidence of STD complications, and increases in antimicrobial resistance.
      For example, human immunodeficiency virus (HIV) emerged to devastate the United
      States with a fatal pandemic involving at least 1 million people. The incidence
      of syphilis rose progressively after 1956 to reach a 40-year peak by 1990. In
      both cases, disease patterns shifted from homosexual men to include minority
      heterosexuals. Over the last decade, gonorrhea became increasingly concentrated
      among adolescents, and several new types of antimicrobial resistance appeared.
      Three interrelated types of environments affect STD patterns. The microbiologic,
      hormonal, and immunologic microenvironments most directly influence
      susceptibility, infectiousness, and development of sequelae. These
      microenvironments are shaped, in part, by the personal environments created by an
      individual's sexual, substance-use, and health-related behaviors. The personal
      environments are also important determinants of acquisition of infection and
      development of sequelae but, in addition, they mediate risk of exposure to
      infection. These are, therefore, the environments that most directly affect
      changing disease patterns. Finally, individuals' personal environments are, in
      turn, molded by powerful macroenvironmental forces, including socioeconomic,
      demographic, geographic, political, epidemiologic, and technological factors.
      Over the past 20 years, the profound changes that have occurred in many aspects
      of the personal environment and the macroenvironment have been reflected in new
      STD patterns.

PMID- 8146136
TI  - Genital human papillomavirus infection.
AB  - Genital human papillomavirus (HPV) infection is a common sexually transmitted
      disease that at the present time is not effectively controlled or treated. Many
      infections are inapparent and transient. However, some HPV infections result in
      persistent lesions that in some cases undergo carcinogenic progression. A subset
      of genital HPVs, designated high-risk types, are preferentially associated with
      high-grade dysplasias and carcinomas. About 90% of cervical cancers contain high
      risk HPV DNA, most often HPV16. Development of a subunit vaccine against high
      risk genital HPVs is a desirable and, it appears, an increasingly feasible long
      term goal. The viral E6 and E7 oncoproteins are selectively maintained and
      expressed in progressed HPV tumors and could potentially be targets for
      therapeutic vaccines. The L1 major virion structural proteins have recently been
      shown to self-assemble into virus-like particles when expressed in insect cells.
      These particles might serve as the basis for a prophylactic vaccine to prevent
      genital HPV infection.

PMID- 8146137
TI  - Herpes simplex virus infections of women and their offspring: implications for a
      developed society.
AB  - Herpes simplex virus infections of humans have been known since ancient times.
      Contemporary society has witnessed a series of devastating manifestations of
      herpes simplex virus infections--namely, genital herpes simplex virus infection
      and neonatal herpes simplex virus infection. With the evolution of society,
      particularly advances in birth control and increasing promiscuity, the
      seroprevalence of herpes simplex virus type 2 infections has increased worldwide,
      however, more so in developed societies. As a consequence, individuals of child
      bearing age are at risk for either reactivation of herpes simplex virus at
      termination of gestation or acquisition of a new primary infection at that time.
      The consequences of vertical transmission of herpes simplex virus from mother to
      child, resulting in neonatal herpes simplex virus infection, can be devastating.
      Current efforts, which are directed toward the treatment of neonatal herpes, have
      established the value of drugs such as vidarabine and acyclovir. However, the
      real emphasis for future programs is the prevention of herpes simplex virus
      infections to avoid person-to-person transmission either horizontally or
      vertically. The development of vaccines directed against herpes simplex virus may
      be of value toward this end.

PMID- 8146138
TI  - Human ecology and behavior and sexually transmitted bacterial infections.
AB  - The three direct determinants of the rate of spread of sexually transmitted
      diseases (STDs) are sexual behaviors, the mean duration of infectiousness, and
      the mean efficiency of sexual transmission of each STD. Underlying ecological and
      behavioral factors that operate through one or more of these direct determinants
      lie on a continuum, ranging from those most proximate back to those more remote
      (in time or mechanism) from the direct determinants. Most remote and least
      modifiable are the historical stages of economic development that even today
      conspicuously influence patterns of sexual behavior. Next are the distribution
      and changing patterns of climate, hygiene, and population density; the global
      population explosion and stages of the demographic transition; and ongoing
      changes in human physiology (e.g., menarche at younger age) and culture (e.g.,
      later marriage). More proximate on the continuum are war, migration, and travel;
      and current policies for economic development and social welfare. Most recent or
      modifiable are technologic and commercial product development (e.g., oral
      contraceptives); circumcision, condom, spermicide, and contraception practices;
      patterns of illicit drug use that influence sexual behaviors; and the
      accessibility, quality, and use of STD health care. These underlying factors help
      explain why the curable bacterial STDs are epidemic in developing countries and
      why the United States is the only industrialized country that has failed to
      control bacterial STDs during the AIDS era.

PMID- 8146140
TI  - Quest for life-long protection by vaccination.
AB  - Life-long protection from disease through immunization can be accomplished
      through individual or community protection. Individual protection is the goal for
      vaccination against diseases that have inanimate or animal reservoirs or that
      pose risks for certain populations. Community protection is the goal for
      vaccination against diseases that are transmitted only from human to human.
      Community protection afforded by childhood vaccines has been highly successful
      against measles, rubella, mumps, and polio. However, outbreaks of measles,
      rubella, and mumps continue to occur, primarily because of inadequate
      immunization of children under age 2. Simplification of vaccination regimens,
      provision of incentives to care providers and parents, and increased access to
      care should improve vaccination rates in the United States. Better protection
      requires better use of available vaccines. Eradication of disease through
      vaccination is the ultimate goal of community protection. Elimination of the
      infectious agent is the most effective means of achieving life-long protection.
      The World Health Organization's (WHO) smallpox eradication campaign eliminated a
      serious disease as well as the need for a vaccine with frequent and severe
      adverse reactions. The discontinuation of smallpox vaccination in the United
      States has produced a savings of over $3 billion. Polio has been targeted by WHO
      for eradication by the year 2000. The eradication of polio and the elimination of
      the need for polio vaccination in the United States should result in a savings of
      $110 million per year in vaccine costs alone. Strong United States support is
      crucial for WHO to reach its goal. Any of the vaccine-preventable childhood virus
      diseases could be eradicated with sufficient national and international will.
      Measles and hepatitis B should be high priorities. The ultimate goal of
      vaccination is life-long protection of all individuals. Any disease of sufficient
      public health importance to warrant routine vaccination is of sufficient
      importance to warrant eradication wherever judged to be possible.

PMID- 8146139
TI  - Vaccines for bacterial sexually transmitted infections: a realistic goal?
AB  - Bacterial infections of the genital tract (gonorrhea, chlamydia, chancroid,
      syphilis) are common and cause significant morbidity. Their importance is
      heightened by recent appreciation of their roles in facilitation of transmission
      of the human immunodeficiency virus (HIV). Each is capable of causing repeated
      infections, suggesting lack of permanent broadly effective immunity. An effective
      vaccine has yet to be developed for any of these diseases. Rapid progress in
      understanding the molecular basis for pathogenesis of infection, including
      mechanisms for escape from otherwise effective immune surveillance and mechanisms
      for causing injury to host cells, has stimulated renewed efforts to make vaccines
      for some of these infections. Progress has been greatest for Neisseria
      gonorrhoeae and Chlamydia trachomatis. Present emphasis is on the major or
      principal outer membrane proteins of N. gonorrhoeae and C. trachomatis, based on
      evidence for neutralizing antibodies directed against surface-exposed variable
      domains of each of these proteins. Other surface-exposed proteins, including the
      iron-repressible transferrin receptor in gonococci and certain heat-shock
      proteins in chlamydia, also may be targets for vaccines. Although much remains to
      be learned, cautious optimism is warranted.

PMID- 8146141
TI  - Sequence and structure comparison suggest that methionine aminopeptidase,
      prolidase, aminopeptidase P, and creatinase share a common fold.
AB  - Amino acid sequence comparison suggests that the structure of Escherichia coli
      methionine aminopeptidase (EC 3.4.11.18) and the C-terminal domain of Pseudomonas
      putida creatinase (EC 3.5.3.3) are related. A detailed comparison of the three
      dimensional folds of the two enzymes confirms this homology: with an
      approximately 260-residue chain segment, 218 C alpha atoms of the structures
      superimpose within 2.5 A; only 41 of these overlapping positions (i.e., 19%)
      feature identical amino acids in the two protein chains. Notwithstanding this
      striking correspondence in structure, methionine aminopeptidase binds and is
      stimulated by Co2+, while creatinase is not a metal-dependent enzyme. Searches of
      protein data banks using sequence and structure-based profiles reveal other
      enzymes, including aminopeptidase P (EC 3.4.11.9), prolidase (EC 3.4.13.9), and
      agropine synthase, that likely share the same "pita-bread" fold common to
      creatinase and methionine aminopeptidase.

PMID- 8146142
TI  - Molecular cloning of bullfrog saxiphilin: a unique relative of the transferrin
      family that binds saxitoxin.
AB  - Plasma and tissue of certain vertebrates contain a protein called saxiphilin that
      specifically binds the neurotoxin saxitoxin with nanomolar affinity. We describe
      the isolation of a cDNA clone of saxiphilin from liver of the North American
      bullfrog (Rana catesbeiana). The cDNA sequence encodes a protein that is
      evolutionarily related to members of the transferrin family of Fe(3+)-binding
      proteins. Pairwise sequence alignment of saxiphilin with various transferrins
      reveals amino acid identity as high as 51% and predicts 14 disulfide bonds that
      are highly conserved. The larger size of saxiphilin (91 kDa) versus serum
      transferrin (approximately 78 kDa) is primarily due to a unique insertion of 144
      residues. This insertion contains a 49-residue domain classified as a type 1
      repetitive element of thyroglobulin, which is shared by a variety of membrane,
      secreted, and extracellular matrix proteins. Saxiphilin also differs from
      transferrins in 9 of 10 highly conserved amino acids in the two homologous
      Fe3+/HCO3-binding sites of transferrin. Identification of saxiphilin implies that
      transferrin-like proteins comprise a diverse superfamily with functions other
      than iron binding.

PMID- 8146143
TI  - Tight genetic linkage between the kdr insecticide resistance trait and a voltage
      sensitive sodium channel gene in the house fly.
AB  - The kdr insecticide resistance trait in the house fly, Musca domestica, confers
      resistance to the rapid paralysis (knockdown) and lethal effects of 1,1,1
      trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and pyrethroids. Flies with the kdr
      trait exhibit reduced neuronal sensitivity to these compounds, which are known to
      act at voltage-sensitive sodium channels of nerve membranes. To test the
      hypothesis that a mutation in a voltage-sensitive sodium channel gene confers the
      kdr phenotype, we have cloned genomic DNA corresponding to a segment of the house
      fly homologue of the para sodium channel gene of Drosophila melanogaster,
      identified restriction-site polymorphisms within this segment between the kdr
      strain 538ge and an inbred insecticide-susceptible lab stain, and developed a
      sensitive polymerase chain reaction-based diagnostic procedure to determine the
      sodium channel genotype of individual flies. A genetic linkage analysis performed
      with these molecular markers shows that the kdr trait is tightly linked (within
      about 1 map unit) to the voltage-sensitive sodium channel gene segment exhibiting
      the DNA sequence polymorphism. These findings provide genetic evidence for a
      mutation at or near a voltage-sensitive sodium channel gene as the basis for kdr
      resistance.

PMID- 8146145
TI  - Floral and ecological isolation between Aquilegia formosa and Aquilegia
      pubescens.
AB  - Habitat preference and pollination syndrome have been suggested as major factors
      in reproductive isolation among plant species. The columbine genus Aquilegia
      contains species that have been used as classic examples of reproductive
      isolation due to ecological and floral factors. In this analysis Aquilegia
      formosa, Aquilegia pubescens, and natural hybrid populations between these two
      species were assayed for genetic and morphological variation. Clinal variation
      was evident for three "random amplified polymorphic DNA" loci and five
      morphological characters along a transect extending from a lower altitude A.
      formosa population, through an intermediate hybrid population, to a higher
      altitude A. pubescens population. Similar clinal variation was also discovered
      for a transect that included A. formosa-like, hybrid, and A. pubescens-like
      populations at a single elevation. The change in the frequency of both sets of
      markers was closely associated with change in habitat. The molecular markers
      indicate the presence of bidirectional introgression between these two species.
      In contrast, there was apparently selection against introgression of four of the
      five alternate floral characters. Selection against the incorporation of floral
      characters from one species into the other species was suggested by the
      introgression of the DNA markers with little or no introgression of the four
      floral characters. These findings suggest the importance of adaptations
      associated with both pollination syndromes and habitat preference on species
      integrity.

PMID- 8146144
TI  - The zinc finger region of the adenovirus E1A transactivating domain complexes
      with the TATA box binding protein.
AB  - The 289R E1A protein of adenovirus transactivates a variety of viral and cellular
      promoters through protein-protein interactions. In earlier studies, mutational
      analyses of the E1A transactivating domain identified residues that are critical
      for transactivation and implied that the zinc finger region of the
      transactivating domain binds a transcription factor. Also, the E1A activation
      domain was found to bind to the TATA box binding protein (TBP) in vitro. Here, we
      tested the significance of the E1A-TBP interaction for E1A transactivation by
      analyzing the effects of conservative substitutions at each of the 49 residues of
      the E1A activation domain. Seven of the substitutions significantly diminished
      TBP binding in vitro. All of these were in the zinc finger region and were
      defective for transactivation in vivo. The perfect correlation between reduced
      TBP binding and transactivation argues strongly that a direct interaction between
      the E1A activation domain and TBP is critical to the mechanism of E1A activation.
      This genetic analysis leads us to further suggest that another factor, which is
      limiting, is also necessary for E1A-mediated transactivation.

PMID- 8146146
TI  - ocs element promoter sequences are activated by auxin and salicylic acid in
      Arabidopsis.
AB  - ocs elements are a group of promoter elements that have been exploited by two
      distinct groups of plant pathogens, Agrobacterium and certain viruses, to express
      genes in plants. We examined the activity of single and multiple ocs elements
      linked to a minimal plant promoter and the uidA reporter gene in transgenic
      Arabidopsis. beta-Glucuronidase activity was detected only in root tips and in
      callus tissue after auxin treatment. A more sensitive assay revealed that auxin
      treatment also increased ocs element activity in aerial parts of the plant,
      although the absolute levels of ocs element activity were greater in roots. The
      response of ocs elements to exogenous auxin began within 1 h. Salicylic acid, a
      disease-resistance signal in plants, also increased ocs element activity in both
      roots and aerial parts of the plant. The question of whether the induction in ocs
      element activity is mediated through auxin and/or salicylic acid signal
      transduction pathways or is part of a more general stress response is discussed.

PMID- 8146147
TI  - Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol
      dehydrogenase: a member of the aldo-keto reductase superfamily.
AB  - The 3.0-A-resolution x-ray structure of rat liver 3 alpha-hydroxysteroid
      dehydrogenase/dihydrodiol dehydrogenase (3 alpha-HSD, EC 1.1.1.50) was determined
      by molecular replacement using human placental aldose reductase as the search
      model. The protein folds into an alpha/beta or triose-phosphate isomerase barrel
      and lacks a canonical Rossmann fold for binding pyridine nucleotide. The
      structure contains a concentration of hydrophobic amino acids that lie in a
      cavity near the top of the barrel and that are presumed to be involved in binding
      hydrophobic substrates (steroids, prostaglandins, and polycyclic aromatic
      hydrocarbons) and inhibitors (nonsteroidal antiinflammatory drugs). At the distal
      end of this cavity lie three residues in close proximity that have been
      implicated in catalysis by site-directed mutagenesis--Tyr-55, Asp-50, and Lys-84.
      Tyr-55 is postulated to act as the general acid. 3 alpha-HSD shares significant
      sequence identity with other HSDs that belong to the aldo-keto reductase
      superfamily and these may show similar architecture. Other members of this family
      include prostaglandin F synthase and rho-crystallin. By contrast, 3 alpha-HSD
      shares no sequence identity with HSDs that are members of the short-chain alcohol
      dehydrogenase family but does contain the Tyr-Xaa-Xaa-Xaa-Lys consensus sequence
      implicated in catalysis in this family. In the 3 alpha-HSD structure these
      residues are on the periphery of the barrel and are unlikely to participate in
      catalysis.

PMID- 8146148
TI  - Isolation and characterization of a fourth Arabidopsis thaliana G-box-binding
      factor, which has similarities to Fos oncoprotein.
AB  - A fourth member of the Arabidopsis G-box-binding factor (GBF) family of bZIP
      proteins, GBF4, has been isolated and characterized. In a manner reminiscent of
      the Fos-related oncoproteins of mammalian systems, GBF4 cannot bind to DNA as a
      homodimer, although it contains a basic region capable of specifically
      recognizing the G-box and G-box-like elements. However, GBF4 can interact with
      GBF2 and GBF3 to bind DNA as heterodimers. Mutagenesis of the leucine zipper of
      GBF4 indicates that the mutation of a single amino acid confers upon the protein
      the ability to recognize the G-box as a homodimer, apparently by altering the
      charge distribution within the leucine zipper.

PMID- 8146149
TI  - Direct selection for a catalytic mechanism from combinatorial antibody libraries.
AB  - Semisynthetic combinatorial antibody library methodology in the phage-display
      format was used to select for a cysteine residue in complementarity-determining
      regions. Libraries were panned with an alpha-phenethyl pyridyl disulfide that
      undergoes disulfide interchange. Out of 10 randomly picked clones, two contained
      an unpaired cysteine, one of which was studied. The antibody catalyzed the
      hydrolysis of the corresponding thioester where the electrophilic carbonyl
      occupies the three-dimensional space that was defined by the reactive sulfur atom
      during selection. The reaction operates by covalent catalysis. Although the
      steady-state rate enhancement relative to the activated thiol ester substrate is
      modest, hydrolysis of the acylated cysteine intermediate is remarkably efficient
      with a catalytic advantage of about four orders of magnitude. The results suggest
      that iterative mechanism-based selection procedures can recapitulate the
      enzymatic mechanisms refined through evolution.

PMID- 8146150
TI  - The alpha subunit of the human granulocyte-macrophage colony-stimulating factor
      receptor signals for glucose transport via a phosphorylation-independent pathway.
AB  - The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is
      composed of an alpha and beta subunit, which together form the high-affinity
      receptor. The alpha subunit by itself binds ligand at low affinity, whereas the
      isolated beta subunit does not bind GM-CSF. It is generally believed that the
      high-affinity receptor is responsible for the multiple functions of GM-CSF and
      that the isolated alpha subunit (GMR alpha) does not transduce a signal. Xenopus
      laevis oocytes injected with RNA encoding human GMR alpha expressed up to 10(10)
      low-affinity sites for GM-CSF (Kd = 6 nM). GM-CSF binding to the alpha subunit
      expressed in Xenopus oocytes caused activation of 2-deoxyglucose transport
      through endogenous glucose transporters. 2-Deoxyglucose transport was stimulated
      by similar low concentrations of GM-CSF in HL-60 leukemia cells as well as normal
      human neutrophils and Xenopus oocytes expressing GMR alpha. Engagement of the
      isolated alpha subunit in oocytes did not lead to protein phosphorylation or
      tyrosine phosphorylation of mitogen-activated protein kinase (MAP kinase).
      Staurosporin and genistein inhibited GM-CSF-induced tyrosine phosphorylation of
      MAP kinase in human neutrophils and HL-60 cells without affecting GM-CSF
      stimulated uptake of 2-deoxyglucose. These results provide direct evidence that
      the isolated alpha subunit signals for hexose transport and can do so without
      engagement of the kinase cascade. Our data also indicate that signaling for
      hexose uptake may occur in a phosphorylation-independent manner in cells
      expressing the high-affinity GM-CSF receptor.

PMID- 8146151
TI  - Utilization of modified surfactant-associated protein B for delivery of DNA to
      airway cells in culture.
AB  - Pulmonary surfactant lines the airway epithelium and creates a potential barrier
      to successful transfection of the epithelium in vivo. Based on the functional
      properties of pulmonary surfactant protein B (SP-B) and the fact that this
      protein is neither toxic nor immunogenic in the airway, we hypothesized that SP-B
      could be modified to deliver DNA to airway cells. We have modified native bovine
      SP-B by the covalent linkage of poly(lysine) (average molecular mass of 3.3 or 10
      kDa) to the N terminus of SP-B and formed complexes between a test plasmid and
      the modified SP-B. Transfection efficiency was determined by transfection of
      pulmonary adenocarcinoma cells (H441) in culture with the test plasmid pCPA-RSV
      followed by measurement of activity of the reporter gene encoding chloramphenicol
      acetyltransferase (CAT). Transfections were performed with DNA.protein complexes
      using poly(lysine)10kDa-SP-B ([Lys]10kDa-SP-B) or poly(lysine)3.3kDa-SP-B
      ([Lys]3.3kDa-SP-B), and results were compared with transfections using unmodified
      poly(lysine).DNA, unmodified SP-B.DNA, or DNA only. For [Lys]10kDa-SP-B.pCPA-RSV
      preparations, CAT activity was readily detectable above the background of
      [Lys]3.3kDa-SP-B or unmodified SP-B. The SP-B-poly(lysine) conjugates were
      effective over a broad range of protein-to-DNA molar ratios, although they were
      optimal at approximately 500:1-1000:1. Transfection efficiency varied with the
      tested cell line but was not specific to airway cells. Addition of replication
      defective adenovirus to the [Lys]10kDa-SP-B.pCPA-RSV complex enhanced CAT
      activity about 30-fold with respect to that produced by the [Lys]10kDa-SP-B.pCPA
      RSV complex alone. This increase suggests routing of the adenoviral.[Lys]10kDa-SP
      B.pCPA-RSV complex through an endosomal pathway. Effects of covalent modification
      on the secondary structure of SP-B were examined by Fourier transform infrared
      spectrometry (FTIR). Results of FTIR indicated that the conformation of
      [Lys]10kDa-SP-B was comprised primarily of alpha-helical structure compared with
      a predominantly aggregated structure of unmodified poly(lysine). We conclude that
      poly(lysine) conjugates of SP-B effectively deliver DNA in vitro and may have
      utility as DNA delivery vehicles to the airway in vivo.

PMID- 8146152
TI  - Recombinational basis of serovar diversity in Salmonella enterica.
AB  - The fliC gene, which encodes phase 1 flagellin, was sequenced in strains of 15
      Salmonella enterica serovars expressing flagellar antigenic factors of the g
      series. The occurrence of each of the flagellin serotypes g,m, m,t, and g,z51 in
      distantly related strains is the result of horizontal exchange of DNA, as
      indicated by identity or close similarity in nucleotide sequence of all or parts
      of the antigenic factor-determining central region of fliC. The flagellin genes
      of some serovars are complex mosaic structures composed of diverse segments
      derived through multiple recombination events. Thus, recombination of
      horizontally transferred segments (intragenic) or entire genes (assortative)
      within and among subspecies is identified as a major evolutionary mechanism
      generating both allelic variation at the fliC locus and serovar diversity in
      natural populations. Evidence that flagellar serological diversity is promoted by
      diversifying selection in adaptation to host immune defense system or
      flagellotropic phage is discussed.

PMID- 8146153
TI  - Residues essential for the function of SecE, a membrane component of the
      Escherichia coli secretion apparatus, are located in a conserved cytoplasmic
      region.
AB  - Protein export in Escherichia coli is absolutely dependent on two integral
      membrane proteins, SecY and SecE. Previous deletion mutagenesis of the secE gene
      showed that only the third of three membrane-spanning segments and a portion of
      the second cytoplasmic region are necessary for its function in protein export.
      Here we further define the residues important for SecE function. Alignment of the
      SecE homologues of various eubacteria reveals that they all contain one membrane
      spanning segment, compared with three in E. coli SecE, and that the most
      conserved region among them lies in their putative cytoplasmic amino termini;
      little homology exists in their membrane-spanning segments. The SecE homologue of
      the extreme thermophilic bacterium Thermotoga maritima was cloned and found to
      complement a deletion of secE in E. coli. Deletion or replacement of the
      cytoplasmic region of E. coli SecE eliminated SecE function, indicating that this
      sequence is essential for a functional secretion machinery. Mutant analysis
      suggests that the most important function of the third membrane-spanning segment
      is to maintain the proper topological arrangement of the conserved cytoplasmic
      domain.

PMID- 8146154
TI  - A molecular model for the genetic and phenotypic characteristics of the mouse
      lethal yellow (Ay) mutation.
AB  - Lethal yellow (Ay) is a mutation at the mouse agouti locus in chromosome 2 that
      causes a number of dominant pleiotropic effects, including a completely yellow
      coat color, obesity, an insulin-resistant type II diabetic condition, and an
      increased propensity to develop a variety of spontaneous and induced tumors.
      Additionally, homozygosity for Ay results in preimplantation lethality, which
      terminates development by the blastocyst stage. The Ay mutation is the result of
      a 170-kb deletion that removes all but the promoter and noncoding first exon of
      another gene called Raly, which lies in the same transcriptional orientation as
      agouti and maps 280 kb proximal to the 3' end of the agouti gene. We present a
      model for the structure of the Ay allele that can explain the dominant
      pleiotropic effects associated with this mutation, as well as the recessive
      lethality, which is unrelated to the agouti gene.

PMID- 8146155
TI  - Lack of expression from a retroviral vector after transduction of murine
      hematopoietic stem cells is associated with methylation in vivo.
AB  - We describe studies of gene transfer and expression of the human
      glucocerebrosidase cDNA by a Moloney murine leukemia virus (MoMuLV)-based
      retroviral vector in a murine gene transfer/bone marrow transplant (BMT) model.
      Pluripotent hematopoietic stem cells (HSCs) were assayed as the colony-forming
      units, spleen (CFU-S) generated after serial transplantation. Transcriptional
      expression from the MoMuLV long-terminal repeat (LTR) was detected at a high
      level in the primary (1 degree) CFU-S and tissues of reconstituted BMT
      recipients. However, we observed transcriptional inactivity of the proviral
      MoMuLV-LTR in > 90% of the secondary (2 degrees) CFU-S and in 100% of the
      tertiary (3 degrees) CFU-S examined. We have compared the methylation status of
      the provirus in the 1 degree CFU-S, which show strong vector expression, to that
      of the transcriptionally inactive provirus in the 2 degrees and 3 degrees CFU-S
      by Southern blot analysis using the methylation-sensitive restriction enzyme Sma
      I. The studies demonstrated a 3- to 4-fold increase in methylation of the Sma I
      site in the proviral LTR of 2 degrees and 3 degrees CFU-S compared to the
      transcriptionally active 1 degree CFU-S. These observations may have important
      implications for future clinical applications of retroviral-mediated gene
      transfer into HSCs, where persistent gene expression would be needed for an
      enduring therapeutic effect.

PMID- 8146156
TI  - Schwann cells transplanted in the lateral ventricles prevent the functional and
      anatomical effects of monocular deprivation in the rat.
AB  - We investigated whether the transplant of Schwann cells prevents the
      physiological and morphological effects of monocular deprivation in the rat. On
      the day of eye opening in rats (postnatal day 14), we transplanted Schwann cells
      in the lateral ventricles and sutured the eyelids of one eye. After 20-30 days,
      at the end of the critical period for the visual system development, we analyzed
      the functional properties of visual cortical neurons. Spontaneous discharge,
      orientation selectivity, and receptive field size of visual cortical neurons in
      transplanted animals were in the normal range. Transplantation of Schwann cells
      prevented the detrimental effects of monocular deprivation on ocular dominance
      and binocularity of cortical neurons. Visual acuity of the deprived eye estimated
      by visually evoked potentials was also normal. Schwann cells derived from adult
      animals were as effective as those derived from neonates. The effects of Schwann
      cells on monocular deprivation were dependent upon the number of cells present in
      the transplant so that 10(6) Schwann cells were sufficient to prevent the effect
      of monocular deprivation, whereas 10(5) and 3.3 x 10(5) Schwann cells were
      ineffective, and 6.3 x 10(5) cells gave variable results. Shrinkage of the
      deprived lateral geniculate neurons was prevented by a transplant of 10(6) cells.
      In rats transplanted with hybridoma cells producing an antibody that functionally
      blocks nerve growth factor (NGF), we found that the effect of cotransplanted
      Schwann cells on monocular deprivation was partly counteracted. We conclude that
      transplantation of Schwann cells prevents both functional and anatomical effects
      of monocular deprivation, presumably acting through the production of NGF. We
      propose that transplants of Schwann cells could be a promising technique for
      clinical applications.

PMID- 8146157
TI  - Lysine synthesis and catabolism are coordinately regulated during tobacco seed
      development.
AB  - The regulation of synthesis and accumulation of the essential amino acid lysine
      was studied in seeds of transgenic tobacco plants expressing, in a seed-specific
      manner, two feedback-insensitive bacterial enzymes: dihydrodipicolinate synthase
      (EC 4.2.1.52) and aspartate kinase (EC 2.7.2.4). High-level expression of the two
      bacterial enzymes resulted in only a slight increase in free lysine accumulation
      at intermediate stages of seed development, while free lysine declined to the low
      level of control plants toward maturity. To test whether enhanced catabolism may
      have contributed to the failure of free lysine to accumulate in seeds of
      transgenic plants, we analyzed the activity of lysine-ketoglutarate reductase (EC
      1.5.1.7), an enzyme that catabolizes lysine into saccharopine. In both the
      control and the transgenic plants, the timing of appearance of lysine
      ketoglutarate reductase activity correlated very closely with that of
      dihydrodipicolinate synthase activity, suggesting that lysine synthesis and
      catabolism were coordinately regulated during seed development. Notably, the
      activity of lysine-ketoglutarate reductase was significantly higher in seeds of
      the transgenic plants than in the controls. Coexpression of both bacterial
      enzymes in the same plant resulted in a significant increase in the proportions
      of lysine and threonine in seed albumins. Apparently, the normal low steady-state
      levels of free lysine and threonine in tobacco seeds may be rate limiting for the
      synthesis of seed proteins, which are relatively rich in these amino acids.

PMID- 8146158
TI  - Light and nutritional regulation of transcripts encoding a wheat protein kinase
      homolog is mediated by cytokinins.
AB  - Many metabolic processes in plants are regulated by phosphorylation of proteins
      by kinases, but little is known of the roles that specific protein kinase play in
      the various signal transduction pathways or the mechanisms by which these kinases
      themselves are regulated. We report here the isolation of a gene, wpk4, encoding
      a putative protein kinase from wheat that appears to belong to the SNF1 kinase
      subfamily and that shows increased transcript levels in response to multiple
      stimuli: light, nutrient deprivation, and cytokinin application. Although wpk4
      mRNA is undetectable in etiolated seedlings, it rapidly accumulates within 1 hr
      of illumination. General nutrient deprivation also increases wpk4 mRNA levels,
      but only under light conditions. In addition, of the various phytohormones
      tested, cytokinin (N6-benzylaminopurine) specifically increases wpk4 mRNA levels
      regardless of the light conditions, whereas in the presence of a cytokinin
      antagonist the level of wpk4 mRNA is not increased by either light or nutrient
      deprivation. These results suggest that the light and nutrient signals that
      induce wpk4 mRNA accumulation may be mediated through cytokinins and provide a
      strong basis for examining the coordinated regulation of protein phosphorylation
      by light, cytokinins, and nutritional cues in a single transduction pathway.

PMID- 8146159
TI  - RanGAP1 induces GTPase activity of nuclear Ras-related Ran.
AB  - The nuclear Ras-related protein Ran binds guanine nucleotide and is involved in
      cell cycle regulation. Models of the signal pathway predict Ran to be active as
      Ran.GTP at the initiation of S phase upon activation by the nucleotide exchange
      factor RCC1 and to be inactivated for the onset of mitosis by hydrolysis of bound
      GTP. Here a nuclear homodimeric 65-kDa protein, RanGAP1, is described, which we
      believe to be the immediate antagonist of RCC1. It was purified from HeLa cell
      lysates and induces GTPase activity of Ran, but not Ras, by more than 3 orders of
      magnitude. The Ran mutant Q69L, modeled after RasQ61L, which is unable to
      hydrolyze bound GTP, is insensitive to RanGAP1.

PMID- 8146160
TI  - Cytolytic and antibacterial activity of synthetic peptides derived from
      amoebapore, the pore-forming peptide of Entamoeba histolytica.
AB  - The pore-forming peptide amoebapore is considered part of the cytolytic armament
      of pathogenic Entamoeba histolytica. Amoebapore is composed of 77 amino acid
      residues arranged in four alpha-helical domains. For structure-function analysis,
      synthetic peptides were constructed corresponding to these four domains: H1
      (residues 1-22), H2 (25-39), H3 (40-64), and H4 (67-77). The peptides H1 and H3,
      representing two highly amphipathic alpha-helical regions of amoebapore,
      possessed pore-forming activity. Peptide H3 displayed cytolytic and antibacterial
      functions similar to those of natural amoebapore. The most potent antibacterial
      activity and the broadest activity spectrum were expressed by H1-Mel, a hybrid
      molecule composed of the N-terminal alpha-helix of amoebapore and the C-terminal
      hexapeptide of melittin from the venom of Apis mellifera.

PMID- 8146161
TI  - Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin
      fibroblasts.
AB  - Oxidative stress of human skin fibroblasts by treatment with ultraviolet A (UVA)
      radiation has been shown to lead to an increase in levels of the heme
      catabolizing enzyme heme oxygenase 1 [heme, hydrogen-donor:oxygen oxidoreductase
      (alpha-methene-oxidizing, hydroxylating), EC 1.14.99.3] and the iron storage
      protein ferritin. Here we show that human skin fibroblasts, preirradiated with
      UVA, sustain less membrane damage during a subsequent exposure to UVA radiation
      than cells that had not been preirradiated. Pretreating cells with heme oxygenase
      1 antisense oligonucleotide inhibited the irradiation-dependent induction of both
      the heme oxygenase I enzyme and ferritin and abolished the protective effect of
      preirradiation. Inhibition of the UVA preirradiation-dependent increase in
      ferritin, but not heme oxygenase, with desferrioxamine also abolished the
      protection. This identifies heme oxygenase 1 as a crucial enzymatic intermediate
      in an oxidant stress-inducible antioxidant defense mechanism, involving ferritin,
      in human skin fibroblasts.

PMID- 8146162
TI  - The human blue opsin promoter directs transgene expression in short-wave cones
      and bipolar cells in the mouse retina.
AB  - Transgenic mouse lines were generated using either 3.8 or 1.1 kb of 5' upstream
      flanking sequence from the human blue opsin gene fused to the lacZ or human
      growth hormone reporter gene. Mice were analyzed for appropriate cell-specific
      and developmental expression patterns. In 13 independently derived lines of
      animals, transgene expression was limited to photoreceptor and inner nuclear
      layer cells. Photoreceptors were identified as cone cells based on morphological
      criteria and colocalization of transgene expression with the cone-associated
      marker, peanut agglutinin lectin. More specifically, transgene-positive
      photoreceptors were identified as short-wave cone cells (S-cones) by using the
      short-wave color opsin-specific antibody, OS-2. Reporter-gene-positive cells of
      the inner nuclear layer were identified as bipolar cells based on morphological
      criteria. Transgenes and the endogenous mouse short-wave opsin gene were
      transcriptionally coactivated at embryonic day 13. These results show that 3.8 or
      1.1 kb of human blue opsin upstream flanking sequences are capable of directing
      expression in short-wave cone cells in a spatially and temporally appropriate
      fashion and that the human blue opsin gene is the homologue of the short-wave
      sensitive pigment, S-opsin, in the short-wave cones of the mouse retina.
      Expression in the bipolar cells may reflect regulatory mechanisms that are common
      to these cells and to the cone photoreceptors.

PMID- 8146164
TI  - Molecular evidence for the origin of birds.
AB  - The major groups of amniote vertebrates appeared during a relatively short time
      span at the end of the Paleozoic Era, a fact that has caused difficulty in
      estimating their relationships. The fossil record suggests that crocodilians are
      the closest living relatives of birds. However, morphological characters and
      molecular sequence data from living amniotes have repeatedly challenged this
      hypothesis by indicating a bird-mammal relationship. DNA sequences from four slow
      evolving genes (mitochondrial 12S and 16S rRNA, tRNAVal, and nuclear alpha
      enolase) now provide strong statistical support for a bird-crocodilian
      relationship.

PMID- 8146163
TI  - Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules
      of rats treated with a renal carcinogen, ferric nitrilotriacetate.
AB  - An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces proximal tubular
      necrosis, a consequence of lipid peroxidation, that finally leads to a high
      incidence of renal adenocarcinoma in rodents. Lipid peroxidation as monitored by
      formation of thiobarbituric acid-reactive substances and free 4-hydroxy-2-nonenal
      (HNE) was observed in the kidney homogenates of rats treated with Fe-NTA. Based
      on the fact that HNE is capable of reacting with cellular proteins, we attempted
      to detect the localization of HNE-modified proteins in rat kidney tissues with an
      immunohistochemical procedure. By means of an immunohistochemical technique using
      polyclonal antibody against the HNE-modified proteins, it was shown that HNE
      modified proteins are formed in the target cells of this carcinogenesis model.
      HNE-modified proteins were detected in the renal proximal tubules 1 hr after i.p.
      administration of Fe-NTA (15 mg of iron per kg). Intense positivity was found in
      the cells with degeneration. After 6 hr, the level of HNE-protein conjugates
      decreased due to the subsequent necrosis. The intensity of the immunochemical
      reaction with HNE-modified proteins increased in parallel with an increase in the
      amounts of thiobartituric acid-reactive substances and free HNE that were found.
      Furthermore, histochemical detection of aldehydes by cold Schiff's reagent
      demonstrated that location of aldehydes was identical to that of the HNE-modified
      proteins determined by immunohistochemical procedures. It would thus appear that
      the production of HNE, a genotoxic and mutagenic aldehyde, and its reaction with
      proteins may play a role in Fe-NTA-induced renal carcinogenesis.

PMID- 8146165
TI  - Fib420: a normal human variant of fibrinogen with two extended alpha chains.
AB  - In fibrinogen, alpha E chains form a subpopulation of alpha subunits that are
      distinguished by a carboxyl extension homologous to the C termini of the other
      two constituent chains: beta and gamma. The molecular mass of alpha E is > 50%
      greater than that of the common alpha subunit, due in part to an extra 236 amino
      acids. These residues are encoded by exon VI, a recently discovered extension of
      the fibrinogen alpha gene. Additional mass is contributed by posttranslational
      processing, including N-glycosylation, which, based on experiments with the
      inhibitor tunicamycin, was found to account in large measure for alpha E
      migration on SDS/PAGE at approximately 110 kDa rather than at its calculated mass
      of 92,843 Da. An antibody specific for the exon VI-encoded domain of alpha E
      (anti-VI) and capable of recognizing alpha E-containing fibrinogen in both native
      and denatured form was generated using a recombinant protein as immunogen. Its
      use in Western blot analysis of fractions of normal human blood (plasma and
      preparations of fibrinogen) revealed a single, sharp, alpha E-containing band
      migrating behind the position of the broad, predominant fibrinogen band, (alpha
      beta gamma)2. Designation of the upper band as Fib420, an approximately 420-kDa
      homodimer of the formula (alpha E beta gamma)2, is based on the overwhelming
      proportion of alpha E subunits (> 80% of the total alpha chains) found in anti-VI
      immunoprecipitable material from hepatoma cell medium. Several lines of evidence
      suggest that the alpha E subunit, alone or incorporated into fibrinogen, is more
      stable than the common alpha chain, a feature of potential clinical importance.

PMID- 8146166
TI  - Preparation and screening of an arrayed human genomic library generated with the
      P1 cloning system.
AB  - We describe here the construction and initial characterization of a 3-fold
      coverage genomic library of the human haploid genome that was prepared using the
      bacteriophage P1 cloning system. The cloned DNA inserts were produced by size
      fractionation of a Sau3AI partial digest of high molecular weight genomic DNA
      isolated from primary cells of human foreskin fibroblasts. The inserts were
      cloned into the pAd10sacBII vector and packaged in vitro into P1 phage. These
      were used to generate recombinant bacterial clones, each of which was picked
      robotically from an agar plate into a well of a 96-well microtiter dish, grown
      overnight, and stored at -70 degrees C. The resulting library, designated DMPC
      HFF#1 series A, consists of approximately 130,000-140,000 recombinant clones that
      were stored in 1500 microtiter dishes. To screen the library, clones were
      combined in a pooling strategy and specific loci were identified by PCR analysis.
      On average, the library contains two or three different clones for each locus
      screened. To date we have identified a total of 17 clones containing the
      hypoxanthine-guanine phosphoribosyltransferase, human serum albumin-human alpha
      fetoprotein, p53, cyclooxygenase I, human apurinic endonuclease, beta-polymerase,
      and DNA ligase I genes. The cloned inserts average 80 kb in size and range from
      70 to 95 kb, with one 49-kb insert and one 62-kb insert.

PMID- 8146167
TI  - Use of genetic recombination as a reporter of gene expression.
AB  - An understanding of the patterns of gene expression in response to specific
      environmental signals can yield insight into a variety of complex biological
      systems such as microbial-host interactions, developmental cycles, cellular
      differentiation, ontogeny, etc. To extend the utility of the reporter gene fusion
      approach to such studies, we have constructed a gene expression reporter cassette
      that permits the generation of transcriptional fusions to tnpR encoding
      resolvase, a site-specific recombinase of the transposable element gamma delta.
      Induction of the transcriptional fusions results in production of resolvase,
      which in turn, catalyzes excision of a linked tetracycline-resistance reporter
      gene flanked by direct repeats of res, the DNA sequences at which resolvase
      functions. The loss of tetracycline resistance in descendant bacteria serves as a
      permanent and heritable marker of prior gene expression. This gene fusion
      approach will allow us to assay the induction of gene expression in as few as one
      cell. Additionally, gene expression can be assayed at a later time and/or
      different place from the inducing environment facilitating the study of gene
      expression in complex environments such as animal tissues.

PMID- 8146169
TI  - Overexpression of the beta 1 thyroid receptor induces differentiation in neuro-2a
      cells.
AB  - To determine the functions of the alpha 1 and beta 1 thyroid hormone receptors
      (TRs) in neural differentiation, we have established stable transfected neuronal
      cell lines (Neuro-2a) that overexpress either TR alpha 1 or TR beta 1. 3,5,3'
      Triiodothyronine (T3) treatment of cells that overexpress TR beta 1 blocks
      proliferation by an arrest of cells in G0/G1 and induces morphological and
      functional differentiation of Neuro-2a cells as indicated by the marked increase
      in the number of perisomatal filopodia-like neurites and in acetylcholinesterase
      (AChE) activity. The effect on AChE activity was dose-dependent, and the time
      course analysis reveals that this effect occurs after 24 hr of T3 treatment, with
      a maximal increase occurring after 48 hr of treatment. The increase of AChE
      activity is paralleled by an increase of AChE mRNAs. Last, we present evidence
      that shows that the effects of T3 on differentiation are independent of its
      effect on proliferation. T3 had no effect on the differentiation of Neuro-2a
      cells that overexpressed TR alpha 1. Our results indicate that TR beta 1 may play
      a key role in the effects of T3 in neuroblastoma cell differentiation.

PMID- 8146168
TI  - A form of immunologic tolerance through impairment of germinal center
      development.
AB  - Primary immunization with the T-cell-dependent antigen (4-hydroxy-3
      nitrophenyl)acetyl (NP) coupled to human serum albumin results in the development
      of two pathways of B-cell development, the extrafollicular pathway and the
      germinal center pathway. Soluble, deaggregated NP-human serum albumin injected
      before immunization results in a marked diminution of clonable higher-affinity
      antibody-forming cell precursors--i.e., a form of immunologic tolerance within
      the secondary B-cell repertoire. We describe here the cellular changes in the
      spleen that underlie this tolerance. Using multiparameter flow cytometry, we show
      that tolerant mice develop far fewer NP-binding, peanut agglutinin-positive, or
      germinal center cells than the control immunized mice; 14 days after challenge
      control spleens have approximately 2 x 10(5) such cell per spleen, whereas the
      tolerant mice have approximately 1 x 10(4) cells. Furthermore, we demonstrate by
      immunohistology a reduction in the number of germinal centers containing lambda
      bearing cells, characteristic of the response of C57BL/6 mice to NP. Taken
      together, these data suggest an impairment of germinal center development in the
      tolerant mice.

PMID- 8146170
TI  - Designing amino acids to determine the local conformations of peptides.
AB  - The local conformations of proteins and peptides are determined by the amino acid
      sequence. However, the 20 amino acids encoded by the genome allow the peptide
      backbone to fold into many conformations, so that even for a small peptide it
      becomes very difficult to predict the three-dimensional structure. By using
      empirical conformational energy calculations, a set of amino acids has been
      designed that would be expected to constrain the conformation of a peptide or a
      protein to one or two local minima. Most of these amino acids are based on
      asymmetric substitutions at the C alpha atom of each residue. The H alpha atom of
      alanine was replaced by various groups: -OCH3, -NCH3, -SCH3, -CONH2, -CONHCH3, 
      CON(CH3)2, -NH.CO.CH3, -phenyl, or -o-(OCH3)phenyl. Several of these new amino
      acids are predicted to fold into unique peptide conformations such as right
      handed alpha-helical, left-handed alpha-helical, or extended. In an attempt to
      produce an amino acid that favored the C(eq)7 conformation (torsion angles: phi =
      -70 degrees and psi = +70 degrees), an extra amide group was added to the C beta
      atom of the asparagine side chain. Conformationally restricted amino acids of
      this type could prove useful for developing new peptide pharmaceuticals,
      catalysts, or polymers.

PMID- 8146171
TI  - Chromophore-assisted laser inactivation of proteins is mediated by the
      photogeneration of free radicals.
AB  - Chromophore-assisted laser inactivation (CALI) is a technique that selectively
      inactivates proteins of interest to elucidate their in vivo functions. This
      method has application to a wide array of biological questions and an
      understanding of its mechanism is required for its judicious application. We
      report here that CALI is not mediated by photoinduced thermal denaturation but by
      photogenerated free radicals. Thermal diffusion calculations suggest that the
      temperature changes resulting from CALI are too small to cause thermal
      denaturation, and Arrhenius plots of CALI are inconsistent with a photothermal
      mechanism. CALI shows an energy dose reciprocity above a threshold and can be
      inhibited by free-radical quenchers, thus demonstrating a photochemical mechanism
      of protein inactivation. The type of quenchers that are effective in inhibiting
      CALI indicates that the active species is a hydrogen abstractor which is not
      derived from molecular oxygen. We suggest that the active free-radical species is
      the hydroxyl radical and its very short lifetime explains the spatial specificity
      of CALI such that half-maximal damage is effected within 15 A from the dye moiety
      and no significant damage occurs at 34 A. The data are consistent with free
      radical formation resulting from a sequential two-photon process.

PMID- 8146172
TI  - Chromophore-assisted laser inactivation of patched protein switches cell fate in
      the larval visual system of Drosophila.
AB  - The Drosophila segment-polarity gene patched (ptc) is an integral component of
      the segmentation gene cascade acting in the early embryo. At later stages of
      embryogenesis, ptc is expressed in the primordia of epithelial placodes of a
      specific portion of the brain, the optic lobes. Mutant analysis shows that the
      lack of ptc activity alters the fate of optic-lobe primordia precursors. In ptc
      mutants they give rise to supernumerary neurons in the larval light-sensory
      system, termed Bolwig organ, which is derived from precursor cells next to the
      optic-lobe anlagen. We specifically eliminated ptc protein by chromophore
      assisted laser inactivation (CALI) in late wild-type embryos. Such embryos show a
      normal segment pattern, but they develop phenocopies equivalent to the phenotype
      of ptc mutant Bolwig organs. Our results demonstrate that the CALI technique can
      be applied to separate genetic functions at different developmental stages of a
      living organism and that the segment-polarity gene ptc is redeployed to
      functionally discriminate between distinct developmental pathways in adjacent
      pools of precursor cells.

PMID- 8146173
TI  - The NodC protein of Azorhizobium caulinodans is an N
      acetylglucosaminyltransferase.
AB  - Nod factors are signal molecules produced by Azorhizobium, Bradyrhizobium, and
      Rhizobium species that trigger nodule formation in leguminous host plants. The
      backbone of Nod factors consists of a beta-1,4-N-acetylglucosamine
      oligosaccharide from which the N-acetyl group at the nonreducing end is replaced
      by a fatty acid. The nodABC gene products are necessary for backbone
      biosynthesis. By incubation of cell extracts from Azorhizobium caulinodans with
      radioactive uridine diphosphate-N-acetylglucosamine, Nod factor precursors were
      identified and characterized as beta-1,4-N-acetylglucosamine oligosaccharides. By
      analysis of different nod gene mutants and by expression of nodC in Escherichia
      coli, the N-acetylglucosaminyltransferase activity was ascribed to the NodC
      protein. The results suggest that the first step in biosynthesis of Nod factors
      is the assembly of the oligosaccharide chain.

PMID- 8146174
TI  - Cloning and functional characterization of a third pituitary adenylate cyclase
      activating polypeptide receptor subtype expressed in insulin-secreting cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide
      belonging to the vasoactive intestinal polypeptide/glucagon/secretin family. It
      is widely distributed in the body, and a variety of biological actions have been
      reported. PACAP exerts its biological effects by binding to specific receptors
      that are coupled to GTP-binding proteins. Recent studies have shown that there is
      a family of PACAP receptors (PACAPRs), and two members of this family have been
      identified. We report here the cloning, functional expression, and tissue
      distribution of a third PACAPR subtype, designated PACAPR-3. The cDNA encoding
      PACAPR-3 has been isolated from a mouse insulin-secreting beta-cell line MIN6
      cDNA library. Mouse PACAPR-3 is a protein of 437 amino acids that has 50% and 51%
      identity with rat PACAP type I and type II receptors, respectively. Expression of
      recombinant mouse PACAPR-3 in mammalian cells shows that it binds to vasoactive
      intestinal polypeptide as well as PACAP-38 and -27, with a slightly higher
      affinity for PACAP-38, and is positively coupled to adenylate cyclase. The
      expression of PACAPR-3 in Xenopus oocytes indicates that calcium-activated
      chloride currents are evoked by PACAP and vasoactive intestinal polypeptide,
      suggesting that PACAPR-3 can also be coupled to phospholipase C. RNA blot
      analysis studies reveal that PACAPR-3 mRNA is expressed at high levels in MIN6,
      at moderate levels in pancreatic islets and other insulin-secreting cell lines,
      HIT-T15 and RINm5F, as well as in the lung, brain, stomach, and colon, and at low
      levels in the heart. Furthermore, insulin secretion from MIN6 cells is
      significantly stimulated by PACAP-38. These results suggest that the diverse
      biological effects of PACAP are mediated by a family of structurally related
      proteins and that PACAPR-3 participates in the regulation of insulin secretion.

PMID- 8146175
TI  - Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway.
AB  - Normal p53 function is required for optimal arrest of cells in the G1 phase of
      the cell cycle following certain types of DNA damage. Loss of this cell cycle
      checkpoint may contribute to tumor development by increasing the number of
      genetic abnormalities in daughter cells following DNA damage. The MDM2 protein is
      an endogenous gene product that binds to the p53 protein and is able to block p53
      mediated transactivation of cotransfected reporter constructs; thus, interactions
      between MDM2 and p53 in this checkpoint pathway following ionizing irradiation
      were examined. Though increases in p53 protein by DNA damage were not abrogated
      by MDM2 overexpression, increased levels of MDM2, resulting either from
      endogenous gene amplification or from transfection of an exogenous expression
      vector, were associated with a reduction in the ability of cells to arrest in G1
      following irradiation. In addition, expression of endogenous MDM2 was enhanced by
      ionizing irradiation at the level of transcription in a p53-dependent fashion.
      These observations demonstrate that MDM2 overexpression can inhibit p53 function
      in a known physiologic pathway and are consistent with the hypothesis that MDM2
      may function in a "feedback loop" mechanism with p53, possibly acting to limit
      the length or severity of the p53-mediated arrest following DNA damage.

PMID- 8146176
TI  - Molecular and physiological alterations in murine ventricular dysfunction.
AB  - The present study reports the development and characterization of a murine model
      of right ventricular dysfunction following graded constriction in the pulmonary
      artery via microsurgical approaches. To analyze in vivo ventricular function, a
      technique of x-ray contrast microangiography was developed to allow the
      quantitative analysis of ventricular volumes and of ejection fraction in normal
      and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial
      banding for 14 days resulted in right ventricular dilatation and dysfunction,
      associated with right atrial enlargement, and angiographic evidence of tricuspid
      regurgitation. These effects were dependent on the extent of hemodynamic
      overload, since more moderate pulmonary arterial constriction resulted in
      hypertrophy with maintenance of right ventricular function. With severe pulmonary
      artery constriction, the murine right ventricle displays a failing heart
      phenotype including chamber dilation with reduced function that resembles right
      ventricular dysfunction in man during chronic pulmonary arterial hypertension.
      Northern and immunoblot analyses demonstrate a marked down-regulation of
      phospholamban mRNA and its corresponding protein with both levels of
      constriction, while a less pronounced but significant depression of sarcoplasmic
      reticulum Ca(2+)-ATPase protein was observed with severe overload, suggesting
      that this pattern is an early genetic marker of ventricular dysfunction. By
      coupling mouse genetics with this murine model and the ability to assess cardiac
      function in vivo, one should be able to test the role of the down-regulation of
      phospholamban and other defined alterations in the cardiac muscle gene program in
      the onset of the failing heart phenotype.

PMID- 8146177
TI  - A mouse B16 melanoma mutant deficient in glycolipids.
AB  - Mouse B16 melanoma cell line, GM-95 (formerly designated as MEC-4), deficient in
      sialyllactosylceramide was examined for its primary defect. Glycolipids from the
      mutant cells were analyzed by high-performance TLC. No glycolipid was detected in
      GM-95 cells, even when total lipid from 10(7) cells was analyzed. In contrast,
      the content of ceramide, a precursor lipid molecule of glycolipids, was normal.
      Thus, the deficiency of glycolipids was attributed to the first glucosylation
      step of ceramide. The ceramide glucosyltransferase (EC 2.4.1.80) activity was not
      detected in GM-95 cells. There was no significant difference of
      sialyllactosylceramide synthase activity, however, between GM-95 and the parental
      cells. The deficiency of glycolipids in GM-95 cells was associated with changes
      of the cellular morphology and growth rate. The parental cells showed irregular
      shapes and tended to overlap each other. On the other hand, GM-95 cells exhibited
      an elongated fibroblastic morphology and parallel arrangement. The population
      doubling times of GM-95 and the parental cells in serum-free medium were 28 hr
      and 19 hr, respectively.

PMID- 8146178
TI  - Transport of newly synthesized glucosylceramide to the plasma membrane by a non
      Golgi pathway.
AB  - High-gradient magnetic affinity chromatography (HIMAC) has been used to obtain
      highly enriched plasma membranes, free of intracellular membrane contaminants,
      from cultured Chinese hamster ovary (CHO) cells in yields of > or = 80%. Using
      this procedure we have characterized the transport of glucosylceramide (GlcCer)
      and the ganglioside GM3 to the plasma membrane. Newly synthesized GlcCer reaches
      the plasma membrane in 7.2 min, whereas GM3 requires 21.5 min to reach the plasma
      membrane. Brefeldin A prevents transport of newly synthesized GM3 and
      sphingomyelin to the plasma membrane but has no effect on the transport of
      GlcCer. Similarly, incubation of CHO cells at 15 degrees C blocks transport of
      GM3 and sphingomyelin to the plasma membrane but has no effect on GlcCer
      movement. We propose that carrier-mediated transport accounts for a major
      fraction of the plasma membrane GlcCer. Pulse-chase studies with either
      [3H]glucose or [3H]palmitate indicate that newly synthesized GlcCer which has
      reached the plasma membrane is not utilized for the synthesis of GM3 but is
      instead rapidly either degraded or converted into an as yet unidentified product.
      Our results indicate that in addition to serving as a precursor for higher
      glycosylation in the Golgi, a major fraction of newly synthesized GlcCer is
      rapidly transported to the plasma membrane by a non-Golgi pathway and then
      rapidly turned over.

PMID- 8146179
TI  - Structure of the human annexin VI gene.
AB  - We report the structure of the human annexin VI gene and compare the intron-exon
      organization with the known structures of the human annexin I and II genes. The
      gene is approximately 60 kbp long and contains 26 exons. Consistent with the
      published annexin VI cDNA sequence, the genomic sequence at the 3' end does not
      contain a canonical polyadenylation signal. The genomic sequence upstream of the
      transcription start site contains TATAA and CAAT motifs. The spatial organization
      of the exons does not reveal any obvious similarities between the two halves of
      the annexin VI gene. Comparison of the intron-exon boundary positions of the
      annexin VI gene with those of annexins I and II reveals that within the repeated
      domains the break points are perfectly conserved except for exon 8, which is one
      codon smaller in annexin II. The corresponding point in the second half of
      annexin VI is represented by two exons, exons 20 and 21. The latter exon is
      alternatively spliced, giving rise to two annexin VI isoforms that differ with
      respect to a 6-amino acid insertion at the start of repeat 7.

PMID- 8146180
TI  - Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman
      disease.
AB  - The genomic sequences encoding the human lysosomal acid lipase/cholesteryl
      esterase (sterol esterase; EC 3.1.1.13) have been isolated and sequenced, and the
      information has been used to identify mutations in both alleles of the gene from
      a patient with Wolman disease, an autosomal recessive lysosomal lipid storage
      disorder. The genomic locus consists of 10 exons spread over 36 kb. The 5'
      flanking region is G+C-rich and has characteristics of a "housekeeping" gene
      promoter. One of the identified mutations involves the insertion of a T residue
      after position 634, resulting in the appearance of an in-frame translation stop
      signal 13 codons downstream. The second mutation is a T-to-C transition at
      nucleotide 638. This results in a leucine-to-proline substitution at amino acid
      179 and is predicted to lead to the disruption of the alpha-helical structure in
      a highly conserved region of the protein. These mutations are each capable of
      completely disrupting the catalytic function of the lysosomal acid cholesteryl
      ester hydrolase; their presence can account for the extreme phenotype of the
      lysosomal lipid storage disorder manifested in members of this patient's family.

PMID- 8146181
TI  - Cloning and analysis of the Saccharomyces cerevisiae MNN9 and MNN1 genes required
      for complex glycosylation of secreted proteins.
AB  - Proteins secreted by the yeast Saccharomyces cerevisiae are usually modified by
      the addition at asparagine-linked glycosylation sites of large heterogeneous
      mannan units that are highly immunogenic. Secreted proteins from mnn1 mnn9 mutant
      strains, in contrast, have homogeneous Man10GlcNAc2 oligosaccharides that lack
      the immunogenic alpha 1,3-mannose linkages. We have cloned and sequenced the MNN9
      and MNN1 genes, both of which encode proteins with the characteristics of type II
      membrane proteins. Mnn9p is a membrane-associated protein with unknown function
      that is required for the addition of the long alpha 1,6-mannose backbone of the
      complex mannan, whereas Mnn1p is most likely the alpha 1,3-mannosyltransferase
      located in the Golgi apparatus.

PMID- 8146182
TI  - Protein S binds to and inhibits factor Xa.
AB  - Although human protein S binds to human factor Va and inhibits prothrombinase
      activity, this inhibition is not totally dependent on factor Va. Hence, we
      investigated possible interaction of protein S with human factor Xa. Factor Xa,
      diisopropylphospho-factor Xa and their biotin derivatives ligand blotted
      specifically to protein S and protein S ligand blotted specifically to factor X
      and factor Xa. Biotinylated factors X and Xa bound to immobilized protein S and,
      reciprocally, protein S bound to immobilized factor Xa with a Kd of approximately
      19 nM. In fluid phase, protein S bound to factor Xa with a Kd of approximately 18
      nM. Protein S at 33 nM reversibly inhibited 50% of factor Xa amidolytic activity.
      Protein S inhibition of prothrombin conversion to thrombin by factor Xa was
      phospholipid-independent and was 1.6 times stimulated by Ca2+ ions. Inhibition of
      prothrombinase activity by protein S was 2.3-fold more potent in the presence of
      factor Va, with 50% inhibition at approximately 8 nM protein S. Protein S
      prolonged the factor Xa one-stage clotting time of protein S-depleted plasma in a
      dose-dependent manner. These data demonstrate mechanisms of anticoagulant action
      for protein S that are independent of activated protein C and that involve direct
      binding to factors Xa and Va and direct inhibition of factor Xa.

PMID- 8146183
TI  - Cell cycle regulation of V(D)J recombination-activating protein RAG-2.
AB  - The antigen receptors of B and T lymphocytes are encoded in multiple germ-line
      DNA segments that are joined during lymphocyte development. The recombination
      activating proteins RAG-1 and RAG-2 are both essential for this process, termed
      V(D)J rearrangement. Phosphorylation of the RAG-2 protein at Thr-490 by one or
      more cyclin-dependent kinases is associated with its rapid degradation. In an
      immature B-cell line and in normal thymocytes, RAG-2 protein accumulates
      preferentially in the G0/G1 phases of the cell cycle and declines by at least 20
      fold before cells enter S phase. The amount of RAG-2 protein remains low
      throughout the S, G2, and M phases. The amount of RAG-1 protein shows
      considerably less fluctuation. The variation in RAG-2 protein is likely to be
      established, at least in part, by a posttranscriptional mechanism. These
      observations suggest that V(D)J rearrangement occurs entirely or preferentially
      within G0/G1.

PMID- 8146184
TI  - An evolutionarily conserved palindrome in the Drosophila Gld promoter directs
      tissue-specific expression.
AB  - A conserved palindromic sequence (Gpal) in the promoter region of the Drosophila
      Gld directs expression of a heterologous reporter gene in transgenic flies to the
      anterior spiracular glands of third instar larvae and to the ejaculatory bulb of
      adult males. The Gld gene is normally expressed at high levels in the anterior
      spiracular glands but is not expressed in the ejaculatory bulb of Drosophila
      melanogaster. However, Gld promoters from other Drosophila species contain the
      Gpal element and express glucose dehydrogenase (GLD) in the adult male
      ejaculatory bulb. A gene fusion composed of the D. melanogaster Gld promoter and
      the lacZ gene is expressed in the anterior spiracular glands of transgenic
      larvae. Mutations of the Gpal sequence element in this gene fusion block
      expression of beta-galactosidase in the anterior spiracular gland. Together these
      experiments demonstrate that Gpal is necessary and sufficient for tissue-specific
      expression in the anterior spiracular glands. Based upon the tissue distribution
      and function of GLD, it is speculated that expression of GLD in the anterior
      spiracular glands represents the ancestral state and that GLD expression in other
      tissues arose as a fortuitous consequence of a shared combinatorial regulatory
      network.

PMID- 8146185
TI  - A family of cellular proteins related to snake venom disintegrins.
AB  - Disintegrins are short soluble integrin ligands that were initially identified in
      snake venom. A previously recognized cellular protein with a disintegrin domain
      was the guinea pig sperm protein PH-30, a protein implicated in sperm-egg
      membrane binding and fusion. Here we present peptide sequences that are
      characteristic for several cellular disintegrin-domain proteins. These peptide
      sequences were deduced from cDNA sequence tags that were generated by polymerase
      chain reaction from various mouse tissue and a mouse muscle cell line. Northern
      blot analysis with four sequence tags revealed distinct mRNA expression patterns.
      Evidently, cellular proteins containing a disintegrin domain define a superfamily
      of potential integrin ligands that are likely to function in important cell-cell
      and cell-matrix interactions.

PMID- 8146186
TI  - Molecular cloning and functional expression of two monocyte chemoattractant
      protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.
AB  - Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of
      cytokines that mediate leukocyte chemotaxis. The potent and specific activation
      of monocytes by MCP-1 may mediate the monocytic infiltration of tissues in
      atherosclerosis and other inflammatory diseases. We have isolated cDNAs that
      encode two MCP-1-specific receptors with alternatively spliced carboxyl tails.
      Expression of the receptors in Xenopus oocytes conferred robust mobilization of
      intracellular calcium in response to nanomolar concentrations of MCP-1 but not to
      related chemokines. The MCP-1 receptors are most closely related to the receptor
      for the chemokines macrophage inflammatory protein 1 alpha and RANTES (regulated
      on activation, normal T expressed and secreted). The identification of the MCP-1
      receptor and cloning of two distinct isoforms provide powerful tools for
      understanding the specificity and signaling mechanisms of this important
      chemokine.

PMID- 8146187
TI  - Evidence for two independent domestications of cattle.
AB  - The origin and taxonomic status of domesticated cattle are controversial. Zebu
      and taurine breeds are differentiated primarily by the presence or absence of a
      hump and have been recognized as separate species (Bos indicus and Bos taurus).
      However, the most widely held view is that both types of cattle derive from a
      single domestication event 8000-10,000 years ago. We have examined mtDNA
      sequences from representatives of six European (taurine) breeds, three Indian
      (zebu) breeds, and four African (three zebu, one taurine) breeds. Similar levels
      of average sequence divergence were observed among animals within each of the
      major continental groups: 0.41% (European), 0.38% (African), and 0.42% (Indian).
      However, the sequences fell into two very distinct geographic lineages that do
      not correspond with the taurine-zebu dichotomy: all European and African breeds
      are in one lineage, and all Indian breeds are in the other. There was little
      indication of breed clustering within either lineage. Application of a molecular
      clock suggests that the two major mtDNA clades diverged at least 200,000, and
      possibly as much as 1 million, years ago. This relatively large divergence is
      interpreted most simply as evidence for two separate domestication events,
      presumably of different subspecies of the aurochs, Bos primigenius. The
      clustering of all African zebu mtDNA sequences within the taurine lineage is
      attributed to ancestral crossbreeding with the earlier B. taurus inhabitants of
      the continent.

PMID- 8146188
TI  - Expression of recombinant human casein kinase II and recombinant heat shock
      protein 90 in Escherichia coli and characterization of their interactions.
AB  - To assess the interaction of human casein kinase II (CKII) with the heat shock
      protein 90 (HSP90) class of chaperone proteins, human CKII alpha and beta
      subunits and beta S2A mutant were expressed and purified separately or from a
      tandem coexpression construct in Escherichia coli. Recombinant human HSP90 beta
      and recombinant yeast HSP90 as His6 constructs were also expressed in and
      purified from E. coli. The rhCKII S2A mutant removed the regulatory beta subunit
      autophosphorylation site but had no effect on catalytic efficiency with peptide
      or protein substrates. As a CKII substrate, recombinant hHSP90 beta displayed a
      Km of 9.8 microM and a kcat of 4.1 min-1 and was phosphorylated to 1.5 mol/mol,
      whereas ryHSP90, lacking the known serine CKII sites of hHSP90, was
      phosphorylated at a 19-fold lower kcat/Km ratio to levels of 0.8 mol/mol. The
      endoplasmic reticulum HSP90 family member Grp94 was phosphorylated to 1.4 mol/mol
      but, in contrast, HSC70 and FKBP25 chaperones were phosphorylated to < 0.01
      mol/mol. Neither phospho nor dephospho forms of hHSP90 showed significant
      activation of CKII toward the peptide substrate RRREEETEEE in contrast to a
      previous report that activation was observed at high molar ratios of chaperone to
      kinase.

PMID- 8146189
TI  - Mapping of the actomyosin interfaces.
AB  - Recombinant DNA methods were used to obtain soluble, undenatured fragments of the
      heavy chain of myosin subfragment 1 (S-1). These fragments were of preselected
      lengths and could include protease-sensitive segments that are destroyed when
      other preparation methods are used. Actin binding by each of the three contiguous
      segments (residues 1-248, 249-524, and 518-722, essentially spanning the entire S
      1 heavy chain) was demonstrated. ATP binding, comparable to that of native S-1,
      was obtained only with a segment consisting of residues 1-524. Competition among
      the various fragments for actin was also studied. The data are discussed in
      relation to the recently reported resolved structure of S-1 [Rayment, I.,
      Rypnieski, R. W., Schmidt-Base, K., Smith, R., Tomchick, D. R., Benning, M. M.,
      Winkelmann, D. A., Wesenberg, G. & Holden, H. M. (1993) Science 261, 50-58].

PMID- 8146190
TI  - The "eRF" clone corresponds to tryptophanyl-tRNA synthetase, not mammalian
      release factor.
AB  - To study the similarity between a putative cloned mammalian release factor (RF)
      and tryptophanyl-tRNA synthetase (TRS), a recombinant rabbit RF fusion protein
      was expressed from prokaryotic expression vectors. Purified fractions of the
      fusion proteins were tested for TRS and RF activities. Addition of the fusion
      protein to a TRS assay increased the binding of tryptophan to tRNA(Trp). However,
      in an assay for RF activity, the addition of the fusion protein resulted in
      release of only 1-3% of formylmethionine from an fMet-tRNA-AUG-ribosome
      intermediate that had been provided with UAAA as message. To confirm this result,
      the coding region of the putative eukaryotic RF clone "eRF" was used for in vitro
      transcription and translation in a rabbit reticulocyte lysate system, resulting
      in the synthesis of a single 56-kDa protein. The influence of this 56-kDa protein
      on the termination of translation directed by tobacco mosaic virus was studied.
      Tobacco mosaic virus RNA produced a major 126-kDa protein and a minor 184-kDa
      readthrough protein in an in vitro translation system. The protein generated from
      the "eRF" coding region did not inhibit biosynthesis of the 184-kDa readthrough
      virus protein. Instead, it increased the yield of both viral proteins. This
      increase was presumably due to its TRS activity. Chromatography of proteins
      derived from human lymphoblasts separated RF from TRS activity. Thus, our results
      indicate that the previously cloned "eRF" clone encodes TRS and that rabbit
      reticulocyte RF activity lies in a different protein.

PMID- 8146191
TI  - Essential role for a heterogeneous nuclear ribonucleoprotein (hnRNP) in
      oogenesis: hrp40 is absent from the germ line in the dorsoventral mutant squid.
AB  - The Drosophila melanogaster hrp40 proteins are abundant nuclear pre-mRNA-binding
      proteins that are similar to the heterogeneous nuclear ribonucleoprotein (hnRNP)
      A/B proteins of vertebrates. Recently, hrp40 has been shown to be encoded by the
      squid gene, which is required for dorsoventral axis formation during oogenesis.
      Eggs and embryos from homozygous squid mothers are severely dorsalized, and
      complete deletion of the squid gene results in lethality. Here we have examined
      the expression and localization of hrp40 in wild-type and squid mutant ovaries.
      Using a monoclonal antibody specific for hrp40, the same isoforms of hrp40 are
      detected in both wild-type and squid ovaries, but the amount of hrp40 is reduced
      in squid ovaries. Furthermore, immunolocalization of hrp40 in wild-type egg
      chambers shows that hrp40 is present in the nurse cells, oocyte, and follicle
      cells. In contrast, in squid mutant egg chambers, hrp40 is absent from the germ
      line-derived nurse cells and oocyte, but it is detected in the somatic follicle
      cells. The absence of hrp40 from the germ-line-derived cells of developing egg
      chambers is likely to lead to the striking dorsalized phenotype of squid eggs. In
      addition, dramatic stage-specific changes in the cellular localization of hrp40
      are seen; the protein found in the nurse cell nuclei during early stages of
      oogenesis migrates to the cytoplasm at later stages. These findings reveal
      dynamic patterns of expression and localization of hnRNP proteins during
      development and provide evidence for an essential role for hnRNP proteins.

PMID- 8146192
TI  - Three-dimensional structures of two plant beta-glucan endohydrolases with
      distinct substrate specificities.
AB  - The three-dimensional structures of (1-->3)-beta-glucanase (EC 3.2.1.39)
      isoenzyme GII and (1-->3,1-->4)-beta-glucanase (EC 3.2.1.73) isoenzyme EII from
      barley have been determined by x-ray crystallography at 2.2- to 2.3-A resolution.
      The two classes of polysaccharide endohydrolase differ in their substrate
      specificity and function. Thus, the (1-->3)-beta-glucanases, which are classified
      amongst the plant "pathogenesis-related proteins," can hydrolyze (1-->3)- and (1-
      >3,1-->6)-beta-glucans of fungal cell walls and may therefore contribute to plant
      defense strategies, while the (1-->3,1-->4)-beta-glucanases function in plant
      cell wall hydrolysis during mobilization of the endosperm in germinating grain or
      during the growth of vegetative tissues. Both enzymes are alpha/beta-barrel
      structures. The catalytic amino acid residues are located within deep grooves
      which extend across the enzymes and which probably bind the substrates. Because
      the polypeptide backbones of the two enzymes are structurally very similar, the
      differences in their substrate specificities, and hence their widely divergent
      functions, have been acquired primarily by amino acid substitutions within the
      groove.

PMID- 8146193
TI  - Nerve growth factor and its low-affinity receptor promote Schwann cell migration.
AB  - Migrating Schwann cells in developing or regenerating peripheral nerves are known
      to express dramatically increased levels of nerve growth factor (NGF) and the low
      affinity NGF receptor (LNGFR). Schwann cells do not express detectable pp140trk,
      the NGF-activated receptor tyrosine kinase which is essential for neuronal
      responses to NGF. The temporal correlation observed in Schwann cells between
      migration and the enhanced expression of NGF and LNGFR suggests that NGF and
      LNGFR may promote Schwann cell migration. To test this possibility, we examined
      the effects of NGF on Schwann cell migration on cryostat sections of biologically
      relevant NGF-poor and NGF-rich substrates--normal or denervated peripheral
      (sciatic) nerve, untreated or pretreated with NGF. Results show that Schwann
      cells migrate more rapidly on denervated than on normal sciatic nerve. Antibodies
      to NGF or to LNGFR strongly, but incompletely, inhibit enhanced migration on
      denervated nerves. Pretreatment of denervated nerve sections with NGF increases
      further the rate of Schwann cell migration. The same antibodies to NGF or to
      LNGFR abolish this response. These results suggest that one function of the
      elevated levels of NGF known to be present in embryonic and regenerating
      peripheral nerves is to promote the migration of Schwann cells. In contrast to
      neurons, where pp140trk appears to be the functionally critical NGF receptor, NGF
      responses in Schwann cells depend on LNGFR.

PMID- 8146194
TI  - Receptor regulation of G-protein palmitoylation.
AB  - Many alpha subunits of heterotrimeric guanine nucleotide-binding regulatory
      proteins (G proteins) are palmitoylated. Exposure of cells to the beta-adrenergic
      agonist isoproterenol increased incorporation of [3H]palmitate specifically into
      alpha s, the alpha subunit that mediates stimulation of adenylyl cyclase. Pulse
      chase experiments suggested that isoproterenol increased turnover of alpha s
      bound palmitate. Mutagenesis of Cys-3 in alpha s or alpha o (a homologous alpha
      subunit) prevented palmitoylation of these proteins. Differing results were
      obtained when mutations of Cys-3 in alpha s or alpha o were expressed in cells
      and assayed for their distribution between soluble and membrane fractions. Some
      alpha subunits, including alpha o, are myristoylated at the amino-terminal
      glycine residue. Mutation of this glycine prevented both myristoylation and
      palmitoylation of alpha o, indicating that myristoylation precedes palmitoylation
      of dually acylated alpha subunits. The amino-terminal sequences and fatty
      acylation properties of dually acylated alpha subunits are strikingly similar to
      those of some members of the Src family of protein-tyrosine kinases. The amino
      terminal sequence Met-Gly-Cys-Xaa-Xaa-Ser/Cys shared by these proteins may
      represent a motif for cotranslational and posttranslational processing that
      includes myristoylation of the glycine residue and reversible palmitoylation of
      the cysteine residue.

PMID- 8146195
TI  - Phenotypic consequences of deletion of the gamma 3, alpha 5, or beta 3 subunit of
      the type A gamma-aminobutyric acid receptor in mice.
AB  - Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the gamma 3, alpha 5, and beta
      3 subunits of the type A gamma-aminobutyric acid receptor, respectively, are
      known to map near the pink-eyed dilution (p) locus in mouse chromosome 7. This
      region shares homology with a segment of human chromosome 15 that is implicated
      in Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3 on
      a panel of p-locus deletions, we have determined that the order of genes within
      this cluster is centromere-p(D15S12h)-Gabrg3-Gabra5-Gabrb3-telom ere. Like
      Gabrb3, neither the Gabra5 nor Gabrg3 gene is functionally imprinted in adult
      mouse brain. Mice deleted for all three subunits die at birth with a cleft
      palate, although there are rare survivors (approximately 5%) that do not have a
      cleft palate but do exhibit a neurological abnormality characterized by tremor,
      jerky gait, and runtiness. We have previously suggested that deficiency of the
      beta 3 subunit may be responsible for the clefting defect. Most notably, however,
      in this report we describe mice carrying two overlapping, complementing p
      deletions that fail to express the gamma 3 transcript, as well as mice from
      another line that express neither the gamma 3 nor alpha 5 transcripts.
      Surprisingly, mice from both of these lines are phenotypically normal and do not
      exhibit any of the neurological symptoms characteristic of the rare survivors
      that are deleted for all three (gamma 3, alpha 5, and beta 3) subunits. These
      mice therefore provide a whole-organism type A gamma-aminobutyric-acid receptor
      background that is devoid of any receptor subtypes that normally contain the
      gamma 3 and/or alpha 5 subunits. The absence of an overt neurological phenotype
      in mice lacking the gamma 3 and/or alpha 5 subunits also suggests that mutations
      in these genes are unlikely to provide useful animal models for Angelman syndrome
      in humans.

PMID- 8146196
TI  - Double replacement: strategy for efficient introduction of subtle mutations into
      the murine Col1a-1 gene by homologous recombination in embryonic stem cells.
AB  - A subtle mutation that rendered type I collagen resistant to mammalian
      collagenase has been introduced into the murine Col1a-1 (recently redesignated
      Cola-1) gene by homologous recombination in embryonic stem (ES) cells. Initially,
      a "hit and run" procedure was used. Since two steps were required for introducing
      each mutation and more than one mutation was to be introduced in the same genomic
      region independently, we have developed a streamlined procedure that involves two
      sequential replacement-type homologous recombination events. In the first step,
      an internal deletion was introduced into the Col1a-1 locus along with the
      positive and negative selectable markers, neo and tk, to mark the region of
      interest. G418-resistant homologous recombinants were isolated and used in the
      second step in which the deleted Col1a-1 allele was replaced with a construct
      containing the desired mutation. Homologous recombinants containing the mutation
      were identified among the Tk- ES clones after selection with FIAU [1-(2-deoxy-2
      fluoro-beta-D-arabinofuranosyl)-5-iodouracil (called fialuridine)]. Approximately
      10% of such clones contained the desired mutation. The double replacement
      procedure greatly reduces the time and amount of work required to introduce
      mutations independently into the same or closely linked regions. Once the
      homologous recombinants derived from the first step are established, the
      introduction of other mutations into the deleted region becomes a one-step
      procedure. For X number of introduced mutations, 2X selections are required with
      the "hit and run" approach, but only X + 1 are required with the double
      replacement method. This innovative procedure could be very useful in studies of
      gene structure and function as well as gene expression and regulation.

PMID- 8146197
TI  - T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase
      by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.
AB  - The T-cell antigen CD28 provides a costimulatory signal that is required for T
      cell proliferation. T-cell receptor zeta/CD3 engagement without CD28 ligation
      leads to a state of nonresponsiveness/anergy, thereby implicating CD28 in the
      control of peripheral tolerance to foreign antigens or tumors. A key unresolved
      question has concerned the mechanism by which CD28 generates intracellular
      signals. Phosphatidylinositol 3-kinase (PI 3-kinase) is a lipid kinase with Src
      homology 2 (SH2) domain(s) that binds to the platelet-derived growth factor
      receptor (PDGF-R), an interaction that is essential for signaling by growth
      factor. In this study, we demonstrate that CD28 binds to PI 3-kinase by means of
      a Y(P)MXM motif within its cytoplasmic tail. CD28-associated PI 3-kinase was
      detected by lipid kinase and HPLC analysis as well as by reconstitution
      experiments with baculoviral-expressed p85 subunit of PI 3-kinase. CD28 bound
      directly to the p85 subunit without the need for the associated p110 subunit.
      Site-directed mutagenesis and peptide competition analysis using Y(P)-MXM
      containing peptides showed that PI 3-kinase bound to a Y(P)MXM motif within the
      CD28 cytoplasmic tail (residues 191-194). Mutation of the Y191 within the motif
      resulted in a complete loss of binding, while mutation of M194 caused partial
      loss of binding. Binding analysis showed that the CD28 Y(P)-MXM motif bound to
      the p85 C- and N-terminal SH2 domains with an affinity comparable to that
      observed for PDGF-R and insulin receptor substrate 1. In terms of signaling, CD28
      ligation induced a dramatic increase in the recruitment and association of PI 3
      kinase with the receptor. CD28 is likely to use PI 3-kinase as the second signal
      leading to T-cell proliferation, an event with implications for anergy and
      peripheral T-cell tolerance.

PMID- 8146198
TI  - The cellular proteins that bind specifically to the Epstein-Barr virus origin of
      plasmid DNA replication belong to a gene family.
AB  - This laboratory has previously reported that a tumor-promoting phorbol ester,
      phorbol 12-myristate 13-acetate ("12-O-tetradecanoylphorbol 13-acetate"), induces
      BJAB cells, a Burkitt lymphoma cell line, to express cellular proteins that bind
      to the origin of plasmid DNA replication (oriP) of Epstein-Barr virus. These oriP
      binding proteins interfere with the EBV-encoded nuclear antigen EBNA-1, which
      binds to oriP in Raji cells. To further characterize these proteins, a lambda
      phage expression cDNA library made from phorbol ester-induced BJAB cells was
      screened for fusion proteins which bind to oriP. Two recombinant phages
      containing sequences encoding beta-galactosidase fusion proteins and designated
      lambda-OBP-1 and lambda-OBP-2 were identified. lambda-OBP-1 and lambda-OBP-2
      contained 0.43 kbp and 0.61 kbp of BJAB cell cDNA, respectively, of which 395 bp
      were shared. Using lambda-OBP-1 as probe, two cDNAs of 1.4 kbp and 1.2 kbp,
      designated OBP-1 and OBP-2, respectively, were isolated. These cDNAs also shared
      the 395-bp sequence at the 3' end. With these cDNAs as probes, Northern blot
      analyses of mRNA from BJAB cells gave 1.4, 2.4, and 3.4-kb bands, but a Southern
      blot of human genomic DNA revealed one band. It is likely that the oriP-binding
      proteins were derived from spliced mRNA(s) of a gene family.

PMID- 8146199
TI  - Neurotensin excites basal forebrain cholinergic neurons: ionic and signal
      transduction mechanisms.
AB  - The whole-cell patch-clamp technique was used to investigate the effect of
      neurotensin on cholinergic neurons cultured from the rat nucleus basalis of
      Meynert. Neurotensin excited the neurons by inducing an initial inward current
      carried, at least in part, by Na+ and by reducing inwardly rectifying K+
      conductance. Reduction of the inwardly rectifying K+ conductance was mediated by
      a pertussis toxin-insensitive G protein.

PMID- 8146200
TI  - Functional dependence of Ca(2+)-activated K+ current on L- and N-type Ca2+
      channels: differences between chicken sympathetic and parasympathetic neurons
      suggest different regulatory mechanisms.
AB  - The influx of Ca2+ ions controls many important processes in excitable cells,
      including the regulation of the gating of Ca(2+)-activated K+ channels (the
      current IK[Ca]). Various IK[Ca] channels contribute to the regulation of the
      action-potential waveform, the repetitive discharge of spikes, and the secretion
      of neurotransmitters. It is thought that large-conductance IK[Ca] channels must
      be closely colocalized with Ca2+ channels (ICa) to be gated by Ca2+ influx. We
      now report that IK[Ca] channels can be preferentially colocalized with
      pharmacologically distinct subtypes of voltage-activated Ca2+ channel and that
      this occurs differently in embryonic chicken sympathetic and parasympathetic
      neurons. The effects of various dihydropyridines and omega-conotoxin on voltage
      activated Ca2+ currents (ICa) and Ca(2+)-activated K+ currents (IK[Ca]) were
      examined by using perforated-patch whole-cell recordings from embryonic chicken
      ciliary and sympathetic ganglion neurons. Application of nifedipine or omega
      conotoxin each caused a 40-60% reduction in ICa, whereas application of S-(-)-BAY
      K 8644 potentiated ICa in ciliary ganglion neurons. But application of omega
      conotoxin had little or no effect on IK[Ca], whereas nifedipine and S-(-)-BAY K
      8644 inhibited and potentiated IK[Ca], respectively. These results indicate that
      IK[Ca] channels are preferentially coupled to L-type, but not to N-type, Ca2+
      channels on chicken ciliary ganglion neurons. Chicken sympathetic neurons also
      express dihydropyridine-sensitive and omega-conotoxin-sensitive components of
      ICa. However, in those cells, application of omega-conotoxin caused a 40-60%
      reduction in IK[Ca], whereas nifedipine reduced IK[Ca] but only in a
      subpopulation of cells. Therefore, IK[Ca] in sympathetic neurons is either
      coupled to N-type Ca2+ channels or is not selectively coupled to a single Ca(2+)
      channel subtype. The preferential coupling of IK[Ca] channels with distinct ICa
      subtypes may be part of a mechanism to allow for selective modulation of
      neurotransmitter release. Preferential coupling may also be important for the
      differentiation and development of vertebrate neurons.

PMID- 8146201
TI  - Primacy of liver glucosensors in the sympathetic response to progressive
      hypoglycemia.
AB  - The impact of hepatic glucose concentration on the sympathetic response to
      progressive hypoglycemia was examined in chronically cannulated conscious male
      dogs (n = 6). Graded hypoglycemia was induced via peripheral insulin infusion (30
      pmol.kg-1.min-1) with either peripheral (PER) or portal (POR) glucose infusion.
      Over the 260-min experimental period, arterial glycemia was adjusted from 5.2 +/-
      0.1 to 2.5 +/- 0.1 mM in decrements of approximately 0.5 mM every 40 min.
      Arterial glycemias were not significantly different between PER and POR at any
      measured level. However, hepatic glycemia was significantly elevated at all times
      during POR (8.4 +/- 0.8 to 3.4 +/- 0.2 mM) when compared to PER (5.2 +/- 0.2 to
      2.5 +/- 0.1 mM). Plasma epinephrine values were significantly greater during PER
      vs. POR at all arterial glycemias below 4.0 mM. At the lowest level of arterial
      glycemia studied (2.5 +/- 0.2 mM) the epinephrine response above basal was 3-fold
      greater for PER (8.7 +/- 1.7 nM) when compared to POR (2.6 +/- 0.6 nM) (P <
      0.01). Plasma norepinephrine results were similar for the two protocols, with PER
      demonstrating a 3-fold greater response above basal when compared to POR at 2.5
      mM arterial glycemia (P < 0.05). While the sympathetic response was markedly
      different between protocols when expressed as a function of arterial glycemia,
      when expressed as a function of hepatic glycemia this discrepancy was largely
      eliminated. This latter observation supports the liver as the primary locus for
      glycemic detection relevant to the sympathoadrenal response when hypoglycemia
      develops slowly--i.e., over a period of 2-3 h. A comparison of the current
      findings with our previous observations suggests that the hepatic glucosensors
      may play a greater role in hypoglycemic counterregulation as the rate of fall in
      glycemia is less.

PMID- 8146202
TI  - Cell adhesion alters gene transcription in chicken embryo brain cells and mouse
      embryonal carcinoma cells.
AB  - To determine whether changes in gene expression occur in embryonic cells as a
      consequence of changes in cellular aggregation, chicken embryo brain (CEB) cells
      isolated from 8-day embryos were allowed to aggregate or prevented from
      aggregating by treatment with anti-neural cell adhesion molecule (N-CAM) Fab'
      fragments. A subtractive hybridization cloning strategy was employed to identify
      genes that might show different levels of expression in the two populations of
      cells. In addition, the transcription rates of a number of genes specifying CAMs
      and transcription factors were directly estimated by using nuclear run-off
      transcription assays. The transcription rates of several genes, including those
      encoding N-CAM, Ng-CAM, alpha-N-catenin, HoxA4 (Hox1.4), a fatty acid-binding
      protein, and a subunit of the mitochondrially encoded cytochrome-c oxidase enzyme
      decreased upon CEB cell aggregation. The transcription rates of several
      previously unidentified genes either increased or decreased upon aggregation,
      while the transcription of other genes remained unchanged. The transcription rate
      of the N-CAM gene was 3.3-fold higher in dissociated than in aggregated CEB
      cells. This rate of transcription also increased when the brain tissue was
      dissociated into single cells and the increased rate was maintained by keeping
      the cells dissociated in the presence of Fab' fragments of antibodies to N-CAM.
      Decreased transcription rates of the N-CAM gene were also observed upon
      aggregation of P19 cells, a mouse embryonal carcinoma cell line. Primary chicken
      embryo liver cells, which aggregate primarily by calcium-dependent adhesion
      mechanisms, did not show changes in the N-CAM gene or in the other genes whose
      transcription rates changed in CEB cells and P19 cells. These observations
      suggest that the types of genes regulated by cell aggregation include those for
      CAMs themselves as well as for transcription factors that may control the
      expression of CAMs and other molecules significant for morphogenesis.

PMID- 8146204
TI  - Monthly prostaglandin bibliography prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8146205
TI  - Platelet-activating factor (PAF): implications for coronary heart and vascular
      diseases.

PMID- 8146203
TI  - Intracellular calcium dependence of gene expression in single T lymphocytes.
AB  - In T lymphocytes, intracellular Ca2+ concentration ([Ca2+]i) rises within seconds
      of T-cell antigen-receptor stimulation and initiates the synthesis and secretion
      of interleukin 2, a cytokine essential for T-cell proliferation and the immune
      response. Using video-imaging techniques, we tracked [Ca2+]i signals in
      individual T cells and measured subsequent expression of a beta-galactosidase
      reporter gene (lacZ) controlled by the NF-AT element of the interleukin 2
      enhancer. [Ca2+]i spikes elicited by monoclonal antibody binding to the CD3
      epsilon subunit of the T-cell receptor were positively correlated with gene
      expression, but varied widely between individual cells and were therefore
      difficult to relate quantitatively to lacZ expression. The [Ca2+]i dependence of
      NF-AT-regulated gene expression was determined by elevating [Ca2+]i with either
      thapsigargin or ionomycin and then "clamping" [Ca2+]i to various, stable levels
      by altering either extracellular [Ca2+] or extracellular [K+]. Raising [Ca2+]i
      from resting levels of 70 nM to between 200 nM and 1.6 microM increased the
      fraction of cells expressing lacZ, with Kd approximately 1 microM. Activation of
      protein kinase C enhanced the [Ca2+]i sensitivity of gene expression (Kd = 210
      nM), whereas stimulation of protein kinase A inhibited [Ca2+]i-dependent gene
      expression. The experiments described here provide single-cell measurements
      linking a second messenger to gene expression in individual cells.

PMID- 8146206
TI  - Alteration of cyclosporine (CsA)-induced nephrotoxicity by gamma linolenic acid
      (GLA) and eicosapentaenoic acid (EPA) in Wistar rats.
AB  - Administration of cyclosporine (CsA), 37.4 microM (45 mg)/Kg, per day for 7 days,
      to Wistar rats, induced decreased creatinine clearance (Ccr) and body weight loss
      (BWL), but it did not induce proteinuria. These changes were associated with
      enhanced urinary thromboxane B2 (TXB2) and diminished 6-keto-PGF1 alpha (6kPGF1
      alpha) and prostaglandin E2 (PGE2) excretions. The augmentation in TXB2 and the
      decrease in PGs highly diminished the ratios of 6kPGF1 alpha/TXB2 and PGE2/TXB2.
      In microscopic sections all of the kidneys were affected to variable degrees.
      When CsA was administered to animals fed for 70 days, prior to the experiment, on
      standard chow (SC) containing evening primrose oil (EPO) or fish oil (FO), 1% and
      10% respectively (EPO contained 9% gamma-linolenic acid (GLA) and FO 5.6%
      eicosapentaenoic acid (EPA)), the nephrotoxic effect of CsA was partially
      prevented. These changes were accompanied by increased ratios of urinary 6kPGF1
      alpha/TXB2 and PGE2/TXB2 excretions. Light microscopic (LM) studies showed that
      rats' kidneys fed on SC containing EPO or FO were not always affected and the
      lesions were of minor importance. In conclusion, these results suggest that EPO
      (GLA) and FO (EPA) could play a beneficial role in the development or the
      modulation of the renal syndrome induced by CsA.

PMID- 8146207
TI  - Adrenic acid delta 4 desaturation and fatty acid composition in liver microsomes
      of spontaneously diabetic Wistar BB rats.
AB  - We examined the delta 4 (n-6) desaturation and the fatty acid composition of
      liver microsomes in the insulin-dependent spontaneously diabetic Wistar Bio
      Breeding (BB) rat. The desaturation of adrenic acid to n-6 docosapentaenoic acid
      was decreased in the normo- and hyperglycemic diabetic rats. Insulin treatment
      with 1.0 IU. 100 g body weight-1 twice a day for 2 days restored the reduced
      activity during the hypoglycemic period. The pattern of responses was similar to
      that of linoleic acid delta 6 and dihomo-gamma-linolenic acid delta 5
      desaturases, with a non-parallel relationship between the desaturation system and
      the glycemia. The microsomal fatty acid composition of BB rat liver reflected
      only partially to the delta 4 desaturation at different states of glycemia.
      Factors other than impaired desaturation system are involved in the fatty acid
      metabolism of spontaneously diabetic rats.

PMID- 8146208
TI  - von Willebrand's disease and hemophilia are associated with diminished
      thromboxane A2 (TXA2) formation in clotting whole blood.
AB  - Von Willebrand's disease (vWd) and hemophilia are associated with hemorrhagic
      diathesis and disturbances in platelet aggregation to vessel wall. We compared
      the time course of thromboxane A2 (TXA2) formation by platelets during
      spontaneous clotting of blood of patients with von Willebrand syndrome and from
      patients with hemophilia A or B with that of healthy controls which were matched
      for sex, age and serum lipid status. In clotting blood of healthy females the
      TXA2 production rose at 37 degrees C in 60 min up to 228.2 +/- 32.3 ng/ml. In
      patients with vWd the TXA2 production at 60 min was significantly lower (129.1 +/
      26.7 ng/ml, p < 0/05). In hemophilia type A and B the TXA2 formation after 5-30
      min was significantly diminished in comparison to healthy male controls (p <
      0.05). From the diminished amount of TXA2 formed during spontaneous clotting of
      whole blood we conclude that the activation of platelets of patients with von
      Willebrand syndrome or hemophilia type A and B is diminished as compared to
      healthy controls possibly caused by reduced formation of thrombin in the blood
      coagulation process.

PMID- 8146209
TI  - Forebrain and hindbrain involvement of neuropeptide Y in ingestive behaviors of
      rats.
AB  - Neuropeptide Y (NPY) is an extremely potent orexigenic agent. These studies
      demonstrate that the effect of NPY on food and water intake are seen after
      infusion into either the third (3V) or fourth (4V) ventricle and that this is a
      specific effect, as it was not seen with the deaminated form. There was a
      nonsignificant tendency for lateral midbrain knife cuts to food intake. Both 3V
      and 4V NPY infusions showed an attenuated increases in food intake at 1 but not 2
      h following NPY infusion in the lateral knife cut rats compared to the sham
      controls. Medical knife cuts resulted in significantly greater food intake in the
      basal state and a lesser increase in food intake in response to NPY infused into
      the 3V. These midbrain data suggest a role for both medical and lateral fibers in
      mediating the effects of NPY on food intake. Lateral fibers appear to be more
      important, but their transection only delays the time of onset of the stimulating
      effect of NPY to the second hour. Lateral knife cuts virtually abolish the effect
      of 4V NPY on stimulating water intake. 3V NPY in the presence of NPY has a less
      clear effect at 1 h, but mildly attenuated the NPY effect on water intake at 2 h
      in lateral knife cut rats. Medial knife cuts slightly attenuate the effect of 3V
      NPY on water intake. However, medial knife cuts markedly increased basal water
      ingestion. These studies demonstrate the importance of neuronal communications
      between third and fourth ventricle associated structures in the modulation of
      ingestive behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146210
TI  - Systemic clonidine increases feeding and wheel running but does not affect rate
      of weight loss in rats subjected to activity-based anorexia.
AB  - Activity-based anorexia (ABA) is an animal model of anorexia nervosa with two
      characteristics of the disorder, decreased food intake and increased activity. We
      have shown that chronic noradrenergic stimulation of the paraventricular
      hypothalamus exacerbates ABA rather than ameliorates it. This study determined if
      peripheral chronic administration of clonidine affects ABA. Rats were implanted
      SC with osmotic minipumps infusion 0, 30, or 300 micrograms/kg/day of clonidine
      and exposed to ABA (1.5 h/day ad lib food, 22.5 h/day ad lib wheel access).
      Results showed that clonidine did not affect the rate of weight loss during ABA,
      but increased food intake at the lower dose and wheel activity at the higher
      dose. It is proposed that increased energy expenditure due to wheel running is
      counteracted by an inhibition of sympathetically mediated diet-induced
      thermogenesis, and that the elevation in running by the higher dose potentially
      increases the risk of developing ABA.

PMID- 8146211
TI  - Amelioration by aniracetam of abnormalities as revealed in choice reaction
      performance and shuttle behavior.
AB  - To delineate the possible effects of aniracetam PO on abnormal behaviors, we
      analyzed disrupted shuttle behavior and choice reaction (CR) performance in both
      aged and juvenile animals subjected to an ischemic (permanent occlusion of both
      carotid arteries)-hypoxic (17-min exposure to 93% N2 and 7% O2 mixture gas) or
      ischemic (20-min occlusion of both carotid arteries) insult and/or treated with
      methamphetamine given IP. Aniracetam at single PO doses of 10 and 30 mg/kg
      significantly decreased the number of incorrect lever pressings induced by IP
      methamphetamine in young adult rats subjected to the CR test battery. A 21-day PO
      regimen with aniracetam (30 mg/kg/day) resulted in an increase in the number of
      correct responses and a decrease in the CR latency as detected in the CR task
      with young adult rats inflicted with an ischemic-hypoxic insult. Aniracetam (1
      100 mg/kg PO) was also evaluated in the electrostimulation-induced
      hyperreactivity assay (an increase in the number of shuttle responses) in both
      juvenile and aged mice subjected to a 20-min ischemic insult; there again a
      significant improvement of performance was clearly observed. The outcomes of
      these behavioral pharmacological analyses suggest that aniracetam has the ability
      to normalize the disrupted behavior, cognition, and self-regulation or decision
      making process in a comprehensive way.

PMID- 8146212
TI  - Chronic lead exposure attenuates ethanol-induced hypoalgesia.
AB  - Adult male rats were exposed to drinking fluid containing either 500 ppm lead
      acetate (group lead), or an equivalent concentration of sodium acetate (group
      control) for 61 days prior to pain reactivity testing using a tail-flick
      procedure. Rats were placed in restraining tubes for a 20 min acclimation period,
      and then baseline tail-flick latencies in response to a radiant heat source were
      measured. Subsequently, half the animals from each group were serially injected
      IP with either 1.0, 2.0, or 3.0 g/kg body weight of a 20% v/v ethanol solution,
      and the other half were injected with an equivalent volume of saline. Tail-flick
      latencies were reassessed at 20-min intervals over the next 2 h. Results
      indicated dose-dependent ethanol-induced hypoalgesia at all doses, but at the two
      higher doses the magnitude of the hypoalgesic response was significantly greater
      in the group control animals than in the group lead animals across the 2-h
      postinjection period. Results are discussed in terms of an attenuation of the
      pharmacological properties of ethanol by lead.

PMID- 8146213
TI  - Extreme posture elevates corticosterone in a forced ambulation model of chronic
      stress in rats.
AB  - The adrenocorticotropin (ACTH), corticosterone, and corticosterone-binding
      globulin (CBG) levels in rats stressed chronically by a method designed to induce
      biomechanical stress were investigated in order to determine the relationship
      between degree of behavioral stress and evoked change in posture during forced
      ambulation and pituitary-adrenocortical hormone secretion. The method consists of
      forcing rats to ambulate and compares rats forced to ambulate in a normal
      (control group) and extreme (experimental) posture. In this method an extreme
      posture of relative extension was assumed by rats forced to ambulate inside a
      rotating cylinder. The numbers of faecal boli produced during forced ambulation
      were determined as a behavioral measure of stress. Rats forced to ambulate in
      cylinders produced more faecal boli while they ambulated than rats forced to
      ambulate on a flat surface. Rats forced to ambulate in cylinders had higher
      resting levels of corticosterone and lower levels of CBG than rats forced to
      ambulate on a flat surface. The higher corticosterone levels were not associated
      with increased ACTH levels. Because adaptation to forced ambulation resulted in
      higher corticosterone and lower CBG levels when exercise is performed in an
      extreme posture, it is suggested that extreme posture is stressful.

PMID- 8146214
TI  - Diazepam potentiation by glycine in pentylenetetrazol seizures is antagonized by
      7-chlorokynurenic acid.
AB  - This study evaluated a possible mechanism by which glycine potentiates the
      activity of diazepam (DZP) and valproic acid (VAL) against the clonic seizures
      induced by pentylenetetrazol (PTZ) in rats. Neither 7-chlorokynurenic acid (7
      CLKYNA) nor strychnine in doses of 10, 50, or 100 nmol ICV significantly altered
      the clonic seizure response to PTZ. However, 7-CLKYNA (100 nmol, ICV), but not
      strychnine (100 nmol, ICV), antagonized the anticonvulsant activity induced by
      coadministration of DZP (1.0 mg/kg, IP) and glycine (40 mmol/kg, PO). Neither 7
      CLKYNA (100 nmol, ICV) nor strychnine (100 nmol, ICV) significantly altered the
      anticonvulsant activity induced by coadministration of VAL and glycine. 7-CLKYNA
      (100 nmol, ICV) had no effect on the anticonvulsant activity of DZP or VAL in the
      absence of glycine. These results provide evidence that the glycine potentiation
      of the anticonvulsant activity of DZP in clonic seizures induced by PTZ may be
      mediated by the strychnine-insensitive glycine receptor.

PMID- 8146215
TI  - Somatic parameters, organ growth, and plasma substrates in weanling rats with
      lateral hypothalamic lesions one month postoperatively.
AB  - Somatic and some metabolic aspects of the syndrome that follows bilateral
      destruction of the lateral hypothalamic area (LHA) have been studied primarily in
      mature rats. Fewer data are available for the weanling rat. Weanling Sprague
      Dawley rats received small (10 mC) bilateral electrolytic lesions (LHAL). Sham
      operated controls were pair-gained to LHAL rats (CON-PG) or fed ad lib (CON
      ADLIB). All rats were killed 1 month after LHAL. Both LHAL and CON-PG weighed
      less, had less carcass fat, and were shorter than CON-ADLIB. Also, LHAL were
      somewhat, but significantly (SIGN), shorter than CON-PG. Rats with LHAL has less
      carcass protein than CON-ADLIB in percent but not in absolute terms. Liver,
      epididymal fat pads, diaphragm, kidneys adrenals, testes, spleen, and heart grew
      SIGN smaller in LHAL vs. CON-ADLIB, but in no instance was there a SIGN
      difference between LHAL and CON-PG. In body weight percentage, some of these
      differences (liver, kidneys, heart) were not SIGN. Both LHAL and CON-PG had
      larger adrenals than CON-ADLIB and both LHAL and CON-PG had SIGN less protein in
      their livers, epididymal fat pads, and diaphragm than CON-ADLIB. In organ weight
      percentage, however, LHAL rats had more protein in their livers and fat pads than
      CON-ADLIB and LHAL rats had less protein in fat pads than CON-PG in absolute but
      not in percent organ weight terms. Plasma glucose was similar in all groups, but
      LHAL had SIGN lower triglycerides and total cholesterol than CON-ADLIB.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8146216
TI  - Effects of components derived from HPLC purification of human satietin on
      ingestion, body weight, and taste aversion in the rat.
AB  - The putative satiety agent human satietin (h-SAT) once thought to be homogenous
      has been separated by high-performance liquid chromatography (HPLC) into
      components designated peak A (P-A, 53%/w) and Peak B (P-B, 47%/w); P-B contains a
      putative satiety agent. In Experiment 1, male Sprague-Dawley rats were divided
      into six (n = 9-11) groups (Grps) and ICV infused: Grp 1, artificial
      cerebrospinal fluid (a-CSF), 10 microliters/rat; Grp 2, albumin (ALB), 53
      micrograms/rat; Grp 3, semipurified (sp) h-SAT (parent compound), 100
      micrograms/rat; Grp 4, P-A, 53 micrograms/rat; Grp 5, P-B, 47 micrograms/rat; and
      Grp 6, P-A+B, 53+47 micrograms/rat, respectively. Compared to Grp 1, food intake,
      the first day postinfusion, was suppressed in Grp 3 (p < 0.01) and equally
      attenuated (p < 0.06) in Grps 5 and 6. Body weight remained suppressed (p < 0.05)
      in Grps 3, 5, and 6 for 3 days and in Grps 3 and 6 (p < 0.05) for an additional 3
      days; Grps 2 and 4 did not differ from Grp 1. These data show P-B suppresses food
      intake comparably to P-A+B and causes a prolonged weight loss. In Experiment 2,
      sph-SAT and a recombination of P-A and P-B was tested for aversiveness using the
      two-bottle test. Both sph-SAT and P-A+B significantly suppressed food intake, but
      only sph-SAT was found to be aversive. These data show that most likely during
      HPLC processing of sph-SAT an aversive component was lost.

PMID- 8146217
TI  - Naloxone facilitates spatial learning in a water-maze task in female, but not
      male, adult nonbreeding meadow voles.
AB  - The present study examined the effects of the opiate antagonist naloxone on
      spatial acquisition and retention in a water-maze task by adult, nonbreeding,
      male and female meadow voles (Microtus pennsylvanicus). Voles were required to
      learn the position of a hidden, submerged platform using distal visual cues.
      There were four trials per day for 6 days. Daily pretraining (15 min before first
      trial) systemic administrations of naloxone (1.0 mg/kg, IP) significantly
      facilitated spatial acquisition in female, but not in male, voles in a water-maze
      task on days 2, 3, and 4. There were two probe tasks given 1 day and 1 week after
      the last training trial. All groups acquired the spatial task by the end of the
      fifth day with no significant effects of naloxone on retention of the spatial
      task. There were also no significant sex differences in acquisition of the
      spatial task and task retention in control, nonbreeding adult voles. It is
      suggested that the lack of sex differences in basal spatial performance may be
      related to the low levels of testosterone in male nonbreeding voles. The obtained
      sex differences in the effects of naloxone on spatial acquisition are considered
      in relation to sex differences in stress, opiate responses, and gonadal steroid
      levels.

PMID- 8146218
TI  - TCDD-induced hypophagia is not explained by nausea.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent known
      anorexigens with an unestablished mechanism of action. In the present study, the
      role of nausea in TCDD-induced hypophagia was assessed by a battery of behavioral
      (conditioned taste aversion [CTA], kaolin consumption, protein selection),
      biochemical (plasma oxytocin), and antiemetic drug intervention
      (trimethobenzamine, metoclopramide) approaches. Moreover, both the most TCDD
      susceptible (Long-Evans [L-E]; IP LD50 approximately 10 micrograms/kg) and the
      most TCDD-resistant (Han/Wistar [H/W]; IP LD50 > 3000 micrograms/kg) rat strains
      were employed in the experiments. L-E rats were exposed to a lethal dose of TCDD
      (50 micrograms/kg), whereas H/W rats were treated with high but nonlethal doses
      (50 or 1000 micrograms/kg). TCDD produced a positive CTA response in H/W rats
      alone. These animals also increased their kaolin consumption more than L-E rats
      of either gender after TCDD exposure. TCDD decreased the proportional intake of
      energy from high-protein diet in female L-E rats, but tended to increase it in
      male L-E and H/W rats. TCDD did not affect plasma oxytocin concentration by
      itself, but potentiated the elevation caused by the positive control compound,
      LiCl, in L-E rats on day 8. Neither antiemetic tested had any detectable
      influence on TCDD-induced wasting. These findings imply that the degree of nausea
      elicited by TCDD in the rat depends on strain and gender. However, nausea has
      only a minor, if at all, causal role in the lethal wasting syndrome
      characteristic of this compound.

PMID- 8146219
TI  - Relationships between arousal and cognition-enhancing effects of oxiracetam.
AB  - Cognition-enhancing effects of no-otropic drugs are currently ascribed to an
      increase in arousal level. In order to test this hypothesis, we studied the
      effects of three doses of oxiracetam (25, 50 and 100 mg/kg IP) on a radial maze
      task and on slow wave sleep (SWS) latency in a familiar environment. The 25- and
      100-mg/kg doses, but not the 50-mg/kg, significantly improved performance in the
      memory task. On the other hand, SWS latency was significantly increased by 50 and
      100 mg/kg, with the effect of the 25-mg/kg dose going in the same direction but
      only approaching significance. These results give only a partial support to the
      "arousal factor hypothesis." Other factors are probably involved in the promnesic
      effects of oxiracetam.

PMID- 8146220
TI  - Comparison of acute subjective and heart rate effects of nicotine intake via
      tobacco smoking versus nasal spray.
AB  - Nicotine is the primary psychoactive constituent of tobacco smoke, but it is not
      clear whether the reinforcing effects of cigarette smoking can be attributed
      solely to nicotine intake. In this study, two groups of male and female smokers
      participated in three sessions involving intermittent exposure to moderate low,
      or no nicotine doses via controlled tobacco smoking ("smoke," n = 20) or measured
      dose nasal spray ("spray," n = 16). Visual analog scales of subjective effects
      (VAS) and heart rate (HR) were obtained within 5 min of each dosing. Plasma
      nicotine levels indicated comparable dosing between methods. For both methods,
      there were significant nicotine dose effects for most subjective measures and HR.
      More importantly, the pattern of effects across doses was virtually identical
      between methods, as nicotine intake via smoking or spray significantly increased
      HR and the VAS scales of Head Rush and Dizzy, decreased Hunger and Desire to
      Smoke, and had no effect on Comfortable, Jittery, or Relaxed. These results
      suggest that rapid nicotine uptake by novel methods may provide effects very
      similar to nicotine intake by smoking.

PMID- 8146221
TI  - Behavioral studies on LEK-8804, a new ergoline derivative with potent 5-HT1A
      receptor agonist and 5-HT2 receptor antagonist activity.
AB  - The 5-HT1A receptor-mediated tail flick response in rats and the 5-HT2 receptor
      mediated head twitch response in mice were used to study the functional activity
      of a new ergoline derivative, 9,10-didehydro-N-(2-propynyl)-6-methylergoline-8
      beta-carboxamide (LEK-8804). LEK-8804 dose-dependently elicited spontaneous tail
      flicks in rats, indicating a full 5-hydroxytryptamine1A (5-HT1A) agonist
      activity. This effect was very similar to that produced by the selective 5-HT1A
      agonist 8-OH-DPAT, both in terms of potency and time-effect relationship, and was
      blocked by the selective 5-HT1A antagonist NAN-190. In contrast, LEK-8804 by
      itself failed to produce head twitches in mice but dose-dependently inhibited the
      5-hydroxytryptophan (5-HTP)-induced behavior. The inhibitory effect of LEK-8804
      upon 5-HTP-induced head twitches was not attenuated by the selective 5-HT1A
      antagonist NAN-190. This indicates that probably not the agonist action on 5-HT1A
      receptors but instead the antagonism on 5-HT2 receptors was involved in the
      inhibition of head twitch response. It is suggested that LEK-8804 is a potent
      full 5-HT1A receptor agonist with possible 5-HT2 receptor antagonist properties.

PMID- 8146222
TI  - Effect of dexfenfluramine on saccharin drinking: behavioural and pharmacological
      studies.
AB  - We have previously reported that the 5-hydroxytryptamine (5-HT) releaser/reuptake
      blocker dexfenfluramine suppresses voluntary ethanol intake. To further analyse
      the generality of these findings, in the present study we examined the effect of
      equivalent doses of dexfenfluramine (0.5-2.5 mg/kg) on the intake of another
      preferred fluid, saccharin. Saccharin was made available for 2 h daily across a
      wide concentration range chosen to promote varying degrees of intake. Following
      stable levels of intake, the behaviour of vehicle-pretreated rats was assessed
      immediately prior to (anticipatory/preparatory phase) and during (consumatory
      phase) saccharin access. These behaviours were compared and contrasted with those
      produced following dexfenfluramine pretreatment at the optimally preferred
      saccharin concentration (0.2%). In a preliminary study the effects of various 5
      HT antagonists were also examined against the dexfenfluramine response. The
      present results suggest that dexfenfluramine produced a dose-related suppression
      of saccharin intake at doses similar to those which reduced ethanol intake.
      However, the magnitude of this suppression was similar across each saccharin
      concentration. Behavioural analysis indicated that the profile of the
      dexfenfluramine (0.5- and 1-mg/kg doses only) suppression of the 0.2% solution
      was similar to that observed in vehicle-pretreated rats presented with saccharin
      solutions of lesser palatability to this concentration. Pharmacological studies
      indicated a 5-HT1 (non-5-HT1C) receptor involvement in the dexfenfluramine
      response. These studies imply that at certain doses dexfenfluramine may produce a
      subtle alteration in the motivation to consume a preferred fluid.

PMID- 8146223
TI  - Insulin, 2-deoxy-D-glucose, and food deprivation as discriminative stimuli in
      rats.
AB  - Using a two-lever drug discrimination procedure, two groups of four rats each
      were trained to discriminate the stimulus effects of 1.0 U/kg insulin or 125
      mg/kg 2-deoxy-D-glucose (2-DG) from saline. A third group was trained to
      discriminate food deprivation produced by feeding 23 h prior to sessions from
      satiation produced by feeding 2 h prior to sessions. Differential responding was
      a direct function of dose or deprivation level in each group. Rats trained to
      discriminate insulin responded as if they had received insulin when they received
      2-DG and vice versa. Insulin and 2-DG produced deprivation-appropriate responding
      in two of four rats trained to discriminate food deprivation. Low insulin and 2
      DG doses produced drug-appropriate responding in rats deprived 47 h, but not in
      rats deprived 23 h. Blood glucose level was altered by the training doses of
      insulin and 2-DG, but not by 23-h deprivation. These results indicate that
      operations that induce feeding produce discriminable stimuli, and that these
      effects overlap or interact. Thus, drug discrimination procedures can be useful
      in the analysis of ingestive behavior.

PMID- 8146224
TI  - Effect of AIT-082, a purine analog, on working memory in normal and aged mice.
AB  - Because working memory is the primary type of memory which is disrupted by
      Alzheimer's disease and stroke and during aging, any therapeutic drug for these
      conditions should improve and/or restore working memory. The win-shift memory
      paradigm has been shown to be an excellent model of working memory. In the
      present study, we examined the effects of a novel purine derivative, 4-[[3-(1,6
      dihydro-6-oxo-9-purin-9-yl)-1- oxopropyl]amino]benzoic acid (AIT-082) and
      physostigmine (PHY) on working memory. Both AIT-082 and PHY improved memory in
      young mice and restored memory in mice with mild age-induced memory deficits;
      however only AID-082 was also effective in subjects with moderate deficits.
      Neither drug improved memory in mice with severe memory deficits. AIT-082
      exhibited effectiveness over a broad dose range (0.5-60 mg/kg), and the effects
      lasted for seven days after a single high-dose drug administration. AIT-082 was
      devoid of any effects on performance variables and has not shown any toxic side
      effects, thus making it an interesting potential treatment for working memory
      deficits associated with aging, strokes, and Alzheimer's disease.

PMID- 8146225
TI  - Hyperactivity in the offspring of nicotine-treated rats: role of the mesolimbic
      and nigrostriatal dopaminergic pathways.
AB  - To evaluate the involvement of the mesolimbic and nigrostriatal dopaminergic
      systems in hyperactivity in offspring of nicotine-treated dams, timed-pregnant
      Sprague-Dawley rats were implanted SC on gestational day 4 with osmotic minipumps
      to receive saline or nicotine (3 or 6 mg/kg/day) for 16 days. Hyperactive and
      nonhyperactive male offspring of nicotine-treated dams as well as nonhyperactive
      offspring of saline-treated dams were selected and sacrificed at day 22
      postnatally. Discrete brain areas (the nucleus accumbens [NAcc], striatum [STR],
      frontal cortex [FC], ventral tegmental area [VTA], and substantia nigra [SN])
      were microdissected for the evaluation of dopamine (DA) concentration and/or the
      D2 receptor subtype. Dopamine concentration was decreased in the VTA and STR but
      was increased in the SN of the hyperactive offspring. The reduction in striatal
      DA level was associated with a reduction in the number of D2 receptors in that
      area. The data suggest a role for the VTA and striatal dopaminergic system in
      offspring hyperactivity.

PMID- 8146226
TI  - Environment-specific reinstatement of amphetamine-mediated hyperdipsia by
      morphine and (-)-norpseudoephedrine.
AB  - In a study designed to determine whether environmental and pharmacological
      stimuli have the ability to take control of amphetamine-mediated hyperdipsia,
      rats were injected with d,l-amphetamine (AMPH; 4 mg/kg, IP) alone or in
      combination with (-)-norpseudoephedrine (NPE; 10 mg/kg, IP) and then returned to
      the home cage or transferred to a distinct environment (test cage). Water intake
      was measured hourly for 3 h, in the absence of food. AMPH treatment lasted for 10
      days, followed by a 6-day extinction phase during which AMPH, but not NPE,
      injections were discontinued. Subsequently, all animals received challenge
      injections: NPE (10 mg/kg) on day 17; AMPH (4 mg/kg) on day 19; and morphine
      (MOR; 1 mg/kg) on day 21. AMPH-mediated hyperdipsia developed in 50% of animals
      and had an early onset in the home cage. NPE prevented the AMPH effects.
      Discontinuation of AMPH treatment promptly normalized drinking in the home cage
      but increased it further in the test cage. Within 6 days of AMPH discontinuation,
      hyperdipsia completely disappeared. It was reinstated, in the test cage alone, by
      a challenge injection of NPE or MOR. We suggest that hyperdipsia is a primary
      AMPH effect, which in some way is counter-acted by a distinct environment. This
      appears to elicit a compensatory mechanism that is revealed in the absence of
      AMPH and is reinstated in a nonspecific way by pharmacological stimuli.

PMID- 8146227
TI  - Effects of ventral striatal 6-OHDA lesions or amphetamine sensitization on
      ethanol consumption in the rat.
AB  - Female rats with continuous access to water and 6% ethanol were given bilateral
      ventral striatal 6-OHDA infusions, which induced pronounced striatal depletions
      of dopamine. The postoperative ethanol consumption of these rats was not
      significantly affected in comparison to vehicle-infused controls. In a second
      experiment, female rats received escalating doses of d-amphetamine over a 5-week
      period (from 1 to 9 mg/kg/injection). Control females were given saline
      injections. Following a 3-month drug-free interval, the females were given access
      to ethanol, the concentration of which was gradually increased from 2% to 12%
      with weekly intervals. Amphetamine-sensitized rats consumed significantly more
      alcohol than the saline-treated controls. Taken together, these results suggest
      that striatal dopaminergic mechanisms, while not necessary for basal ethanol
      drinking, can facilitate alcohol drinking.

PMID- 8146228
TI  - Ethanol enhancement of GABA-induced 36Cl- influx does not involve changes in
      Ca2+.
AB  - The effect of changes in intracellular Ca2+ on ethanol enhancement of GABA
      mediated 36Cl- influx was investigated in mammalian cortical neurons in culture.
      Ethanol potentiated the effect of submaximal concentrations of GABA on the 36Cl-
      influx, and at 50 mM ethanol directly activated 36Cl- influx in these neurons.
      Pretreatment of the neurons with dantrolene (an agent that depletes intracellular
      Ca2+) and the Ca2+ ionophore, A 23187, did not alter the effect of GABA or
      ethanol enhancement of GABA-mediated 36Cl- influx. Together, these results
      suggest that changes in intracellular Ca2+ are not involved in ethanol modulation
      of GABAAergic responses in cortical neurons.

PMID- 8146229
TI  - Influence of zolpidem, a novel hypnotic, on the intermediate-stage and
      paradoxical sleep in the rat.
AB  - Paradoxical sleep (PS) in mice, rats, and cats is preceded and sometimes followed
      by a short-lasting stage characterized by cortical high-amplitude spindles and
      hippocampal low-frequency theta rhythm. This intermediate stage (IS) seems to
      correspond to a transient functional disconnection of the forebrain from the
      brainstem. Pentobarbital and benzodiazepines greatly extend IS at the expense of
      PS, which is suppressed. Zolpidem, a new imidazopyridine hypnotic, was studied at
      2.5, 5, and 7.5 mg/kg IP. At 2.5 mg/kg, which is already a true hypnotic dose, it
      only decreased PS during the first 2 h of recording with a rebound during the
      following 4 h of recording. At 5 mg/kg, zolpidem increased the number and total
      duration of IS episodes, increased IS episodes not followed by PS, and increased
      PS latency of occurrence. PS amount was decreased during the first three h with a
      rebound in the next 3 h. At 7.5 mg/kg, the total amount of PS was also decreased.
      The eye movement number and theta rhythm frequency of PS were unchanged. These
      results show that zolpidem produces less disruption of the association between IS
      and PS than do previous hypnotics.

PMID- 8146230
TI  - Deoxynivalenol (vomitoxin)-induced conditioned taste aversions in rats are
      mediated by the chemosensitive area postrema.
AB  - The present experiments used a conditioned aversion to a novel saccharin taste to
      assess the aversive effects of deoxynivalenol (vomitoxin) administration, and to
      examine the putative mediating role of the chemosensitive area postrema (AP). In
      experiment 1 adult male rats drank a novel 0.15% saccharin solution followed by
      injection of deoxynivalenol (n = 7; 0.125 mg/kg, IP) or vehicle (n = 7; propylene
      glycol, 0.5 ml/kg). In subsequent two-bottle preference tests the rats
      conditioned with deoxynivalenol displayed significantly (p < 0.01) lower absolute
      and relative saccharin intake levels in comparison to control rats which
      exhibited a strong preference for saccharin solution. In experiment 2 adult male
      rats received area postrema ablations (n = 6) or sham lesions (n = 6). On two
      conditioning days all rats drank a novel 0.15% saccharin solution followed by
      injections of deoxynivalenol (0.125 mg/kg, IP). In subsequent two-bottle
      preference tests the sham-lesioned rats displayed a significant (p < 0.01)
      aversion to the saccharin stimulus, relative to the area postrema-ablated rats
      which exhibited a preference for the saccharin solution. Thus, systemic
      administration of deoxynivalenol, following a novel taste, induced conditioned
      taste aversions which were mediated by the area postrema.

PMID- 8146231
TI  - Alcohol consumption by C57BL/6, BALB/c, and DBA/2 mice in a limited access
      paradigm.
AB  - Alcohol consumption by three inbred mice strains in a limited access condition
      was examined. Access to "Richter" tubes containing alcohol solution was
      restricted to 60 min per day in a drinking cage. Alcohol solution was given in
      escalating concentrations starting at 3% and ending at 12% w/v over several days.
      During the 12% phase, C57 mice consumed an average of 1.68 g/kg, while BALB and
      DBA mice consumed an average of 0.66 and 0.25 g/kg, respectively. The C57BL/6
      mice achieved an average blood alcohol level (BAL) of 60 mg%, whereas the other
      two strains displayed negligible levels. The relationship between alcohol intake
      in a continuous and limited access as well as the utility of the limited access
      paradigm are discussed.

PMID- 8146232
TI  - Changes in food-maintained progressive-ratio responding of rats following chronic
      buprenorphine or methadone administration.
AB  - Seven rats lever pressed under a progressive ratio 3 (PR 3) schedule of food
      presentation; the number of responses per reinforcer systematically increased
      during each session. Break point (i.e., the number of responses in the last
      completed ratio before session termination) was measured under daily methadone
      (4.5 mg/kg and 3.0 mg/kg) or buprenorphine (0.3 mg/kg) administered prior to
      experimental sessions. Both drugs initially eliminated rats' food-maintained
      progressive-ratio responding. Break points during chronic methadone did not
      return to baseline levels after 80 drug sessions and a dose reduction. In
      contrast, break points during chronic buprenorphine administration were
      considerably above baseline control levels for two rats and returned to baseline
      levels for the third.

PMID- 8146233
TI  - Spatial and temporal response properties of residual vision in a case of
      hemianopia.
AB  - Residual vision in subjects with damage of the primary visual cortex (striate
      cortex) has been demonstrated in many previous studies and is taken to reflect
      the properties of known subcortical and extrastriate visual pathways. In this
      report we describe psychophysical experiments carried out on a subject clinically
      blind in half of his visual field (i.e. homonymous hemianopia) caused by striate
      cortex damage. They reveal the existence of two distinct channels mediating such
      vision. One channel responds to spatial structure and the other to light flux
      changes. The spatially tuned channel has a peak response at about 1.2 cycles per
      degree and shows rapid loss of sensitivity at both high and low spatial
      frequencies. This channel does not respond to diffuse illumination. The light
      flux channel, however, responds only to sudden increments in light flux levels on
      the retina and shows extensive spatial summation. Both channels require transient
      inputs, with a peak sensitivity at about 10 cycles per second and show virtually
      complete attenuation at temporal frequencies below 2 cycles per second. The
      spatiotemporal characteristics of these two channels account for much of the
      reported limits of visual performance attributed to subcortical or extrastriate
      pathways in some patients, and especially for their relatively good sensitivity
      for the detection of abrupt, transient stimuli or fast-moving targets. A new
      method is also applied to the measurement of the amount of light scatter in the
      eye. The measurements show that light scatter into the sighted hemifield could
      not account for the results obtained with the stimuli used to characterized the
      residual vision of this subject.

PMID- 8146234
TI  - Dynamics of the CA3 pyramidal neuron autoassociative memory network in the
      hippocampus.
AB  - A theory for the dynamics of sparse associative memory has been applied to the
      CA3 pyramidal recurrent network in the hippocampus. The CA3 region is modelled as
      a network of pyramidal neurons randomly connected through their recurrent
      collaterals. Both the elliptical spread of the axonal systems and the exponential
      decrease in connectivity with distance are taken into account in estimating the
      connection probabilities. Pyramidal neurons also receive connections from
      inhibitory interneurons which occur in large numbers throughout the network;
      these in turn receive inputs from other inhibitory interneurons and from
      pyramidal neurons. These inhibitory neurons are modelled as rapidly acting linear
      devices which produce outputs proportional to their inputs; they perform an
      important regulatory function in the setting of the membrane potentials of the
      pyramidal neurons. The probability of a neuron firing in a stored memory, which
      determines the average number of neurons active when a memory is recalled, can be
      set at will. Memories are stored at the recurrent collateral synapses using a two
      valued Hebbian. Allowance is made in the theory both for the spatial correlations
      between the learned strengths of the recurrent collateral synapses and temporal
      correlations between the state of the network and these synaptic strengths. The
      recall of a memory begins with the firing of a set of CA3 pyramidal neurons that
      overlap with the memory to be recalled as well as the firing of a set of
      pyramidal neurons not in the memory to be recalled; the firing of both sets of
      neurons is probably induced by synapses formed on CA3 neurons by perforant
      pathway axons. The firing of different sets of pyramidal neurons then evolves by
      discrete synchronous steps. The CA3 recurrent network is shown to retrieve
      memories under specific conditions of the setting of the membrane potential of
      the pyramidal neurons by inhibitory interneurons. The adjustable parameters in
      the theory have been assigned values in accord with the known physiology of the
      CA3 region. Certain levels of overlap between the input and the memory to be
      retrieved must also be satisfied for almost complete retrieval. The number of
      memories which can be stored and retrieved without degradation is primarily a
      function of the number of active neurons when a memory is recalled and the degree
      of connectivity in the network. The inhomogeneity in the connectivity of the
      pyramidal cells improves both capacity and overlap of the final state with the
      memory.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8146235
TI  - Long range afferents in rat spinal cord. III. Failure of impulse transmission in
      axons and relief of the failure after rhizotomy of dorsal roots.
AB  - Dorsal root afferents entering the spinal cord form a T-junction with a caudal
      branch descending many segments and giving off side branches terminating in the
      dorsal horn. This anatomical finding contrasts with the physiological observation
      that the postsynaptic effects of arriving afferents in the dorsal horn are
      limited to a few segments on either side of the root carrying the input. This
      paper explores the possibility that one explanation for this paradox is that
      orthodromic impulse conduction fails to penetrate the long range parts of the
      caudal branch. The experiments show that when all roots are intact, very few
      fibres can be detected carrying orthodromic impulses as far as 20 mm caudal to
      the entry point. After section of neighbouring dorsal roots, however, large
      numbers of conducting fibres can be recorded at that point. Signs of orthodromic
      conduction begin 7 days after root section. These results were confirmed by
      another method which compared the relative refractory period of the membrane of
      the descending branch produced either after a local stimulus had evoked an action
      potential or after a rostral distant stimulus had produced an orthodromic action
      potential. Again, in the intact cord, the results indicate that impulses fail to
      penetrate long distances into the descending branches but that, as soon as 2 days
      after rhizotomy in the area of suspected conduction failure, orthodromic
      conduction is restored. It is proposed that the failure and release of conduction
      may depend on the control of membrane potential in the primary afferents, which
      would form a pre-presynaptic control mechanism.

PMID- 8146236
TI  - The Croonian Lecture, 1993. The endothelium: maestro of the blood circulation.
AB  - The vascular endothelium plays a vital role in the control of the circulation. It
      metabolizes various vasoactive substances, coverts angiotensin I to angiotensin
      II and secretes the potent vasodilators prostacyclin and EDRF (NO) and the
      vasoconstrictor peptide endothelin-1. The balance between these mediators
      determines the responses of the cardiovascular system in diseases such as
      hypertension, atherosclerosis and myocardial infarction.

PMID- 8146237
TI  - [Therapeutic strategies with drugs].

PMID- 8146238
TI  - [Withdrawal treatment of drug dependent patients with the aim of achieving
      abstinence].
AB  - The treatment of patients who are dependent on drugs is undergoing a conceptual
      change, and in this connection more attention is being paid to a qualified
      withdrawal and weaning. More than 200 withdrawals are being performed annually in
      the U2 section of the Department of Psychiatry of the University of Basel. The
      authors report on the composition of the patient groups, their withdrawal
      symptoms and the therapy offered. In respect of the continually too frequent
      discontinuations of therapy attention is drawn to the need for a really efficient
      pharmacotherapy.

PMID- 8146239
TI  - [Qualified inpatient acute treatment of drug dependent patients in North Rhine
      Westphalia].
AB  - Qualified concepts of clinical treatment of drug addicts in the Federal Republic
      of Germany have been put into practice to a large extent only in terms of
      abstinence oriented long term therapy (in the FRG called disuse therapy).
      Specialized and differentiated offers of clinical acute treatment, which is
      orientated to the special regards of treating groups of drug addicts not yet
      accessible to therapy, are to be found singularily in Munich, Hamburg, Luneburg,
      and in the State of North Rhine-Westphalia. There are to be discussed experiences
      with a special setting of medicament assisted acute treatment, which is embedded
      in a motivation enforcing social therapeutical and psychotherapeutical concepts
      attaining all psychically and physically ill drug addicts willing to start a
      therapy. This standard offer has to be integrated in the regional drug aid
      network.

PMID- 8146240
TI  - [Management of drug dependent patients in Offenbach/Main and experiences with
      after-care at the psychiatric department of urban clinics].
AB  - The report describes the inpatient and out-patient treatment facilities for
      alcoholics in a defined catchment area and the experience gathered by the
      initiation of out-patient group therapy for a group of alcoholics at the general
      community hospital in Offenbach/Main. The goal of the group therapy at the
      hospital was to establish post-withdrawal treatment care for alcoholics after
      short-term clinical and long-term sanatorium withdrawals. It was hoped that group
      therapy experience would reduce the high drop-out rate of patients after
      hospitalization and after long-term sanatorium treatment, especially by patients
      with more severe social or psychic disorders. Experience showed that those
      capable of group therapy maintained contact to the group, others, the main target
      group of patients took little advantage of the therapy offered.

PMID- 8146241
TI  - [The implications of age at onset of chronic alcoholism--an overview].
AB  - This paper gives a short review about the available literature concerning the
      impacts of age of alcoholism onset. Empirical studies of the last twenty years
      have mainly tried to find differences between onset during youth and the middle
      age. There are only few reports about specific characteristics of patients, who
      have developed alcoholism in their older age. Biological and psychosocial
      findings and therapeutic considerations are described. Their account on further
      research and practical care are discussed.

PMID- 8146242
TI  - [Demands and reality in the rehabilitation of psychiatric patients. Results of a
      follow-up study in established need for rehabilitation with reference to the
      housing and/or vocational sphere].
AB  - At an index day all 166 patients of the Department of General Psychiatry were
      asked whether changes of working or housing condition were considered necessary
      and which definite steps had to be done. In 85 (51.2%) of 166 patients changes
      were considered necessary. What measures had been initiated or carried out?
      Concerning the housing situation age and disease (psychiatric diagnosis) proved
      to be important factors; concerning the working situation age, sex, socioeconomic
      status and length of unemployment were important.

PMID- 8146243
TI  - [Is drug prohibition an effective tool? An analysis from the forensic viewpoint].
AB  - The effectivity of prohibiting the use of drugs is discussed against the
      background of crimes committed in connection with drugs. The theoretical and
      possible practical consequences of liberalisation are presented under legal
      aspects in respect of criminal offence in the wake of drug abuse. Since the
      concepts applied so far have been largely unsuccessful, it is high time to try
      out new approaches to the problem.

PMID- 8146244
TI  - [Psychiatric management of mentally handicapped patients. A systemic model].
AB  - The care for mentally handicapped subjects in a geographically, linguistically
      and socioculturally well defined region of Switzerland (the region "Oberwallis")
      is described. The care and the treatment are following a systemic model. The
      mentally handicapped live outside the psychiatric hospital in social integrated
      housing and working structures, which are established by an autonomous organized
      association. There exists a close cooperation between this association and the
      psychiatric hospital, which is integrated in a general hospital. Both
      institutions, the common theoretical basis and forms of cooperation are
      described.

PMID- 8146245
TI  - [Problems in the perception of sexual self-determination: a neglected problem in
      manic patients?].

PMID- 8146246
TI  - [Substitution as a possibility for the treatment of opiate dependent patients].
AB  - The treatment of patients who are dependent on opiates has definitely been
      including drug substitution besides withdrawal and weaning in the Swiss urban
      community ("Kanton") of Basel City since 1980. After a significant increase of
      treatments in 1987 in connection with the spread of HIV infections, more than 800
      patients were presently receiving substitution treatment according to a
      descentralised schedule. The type of long-term treatment is illustrated by
      sociodemographic and treatment data of 500 substituted individuals who are mostly
      being looked after always by the same persons entrusted with caring for them.
      This represents a flexible, economically feasible and highly individual type of
      care and treatment that can help to reduce illegal drug consumption and hence the
      undesirable events associated with it in an urban district such as Basel city.

PMID- 8146247
TI  - Preferential neural processing of attended stimuli in attention-deficit
      hyperactivity disorder and normal boys.
AB  - Event-related auditory and visual potentials were recorded from 36 attention
      deficit hyperactivity disorder (ADHD) and 35 normal 6-year-old subjects engaged
      in a two-choice discrimination task. When normal subjects attended to stimuli in
      a given modality, enhanced negative (N2) and positive (P3b) responses (as
      compared with responses to nonattended stimuli) were found for auditory and
      visual target stimuli. In contrast, when ADHD subjects attended, little or no
      enhanced negative responses were found in either modality, and enhanced positive
      P3b responses were found only in response to visual target stimuli. Auditory N1,
      N2, and P3b and visual N2 amplitudes to attended target stimuli were
      significantly reduced in ADHD subjects as compared with normal subjects. No
      between-group differences were found for responses to nonattended stimuli. Both
      amplitude and latency abnormalities indicate that ADHD boys suffer from deficient
      preferential processing of attended stimuli. P3b and N2 abnormalities found here
      suggest deficiencies in two independent cognitive processes thought to be crucial
      to what we perceive, learn, and remember.

PMID- 8146248
TI  - Emotional qualities of odors and their influence on the startle reflex in humans.
AB  - Recent human and animal research suggests that the startle reflex might serve as
      a psychophysiological indicator of the emotional valence of foreground
      stimulation. The present experiment was designed to evaluate the emotional
      effects of positive and negative odorant stimuli. We examined the effects of
      continuous hydrogen sulphide (H2S) and vanillin stimulation on the magnitude of
      the acoustic startle reflex (measured at the M. orbicularis oculi) and on ratings
      of subjective valence in 16 healthy subjects. In accordance with the view that
      odors have emotional qualities, we found that H2S, a presumed negative foreground
      stimulus, significantly enhanced the startle-reflex amplitude relative to neutral
      air stimulation, whereas vanillin, a positive foreground stimulus, tended to
      reduce the reflex amplitude compared with neutral air stimulation. Both odorant
      stimuli were rated as equally intense by the subjects, and heart rate and
      electrodermal activity were not affected differentially by the two odorants.

PMID- 8146249
TI  - Parasympathetic nervous system control of heart rate responses to stress in
      offspring of hypertensives.
AB  - The elevated heart rate response to stress in normotensive offspring of
      hypertensives (PH+) has been suggested to be a function of sympathetic nervous
      system activity. This study examined whether parasympathetic nervous system
      activity may also underlie familial differences in the heart rate response.
      Twenty-four subjects, half of whom were PH+, were exposed to four stressor tasks
      administered in counterbalanced order. Stressors were chosen based on previous
      research that suggested vagal contributions to the heart rate response. Stressors
      were a cold pack to the forehead, isometric hand grip, a noxious film, and a
      shock-avoidance video game task. Physiological measures included heart rate (HR),
      respiration rate (RR), and respiratory sinus arrhythmia (RSA). RSA values were
      corrected for corresponding RR by analysis of covariance. Familial differences in
      HR were observed in response to the hand grip and video game tasks. However, in
      both cases analyses suggest that familial differences in reactivity were a
      function of primarily sympathetic as opposed to parasympathetic influences.
      Familial differences in RSA were not observed for rest or tasks. This study found
      no evidence for parasympathetic mediation of familial differences in the heart
      rate response to the stressors employed.

PMID- 8146250
TI  - Cardiac vagal tone and sustained attention in school-age children.
AB  - Three hypotheses tested relationships between cardiac responses mediated via the
      vagus and sustained attention in a population of normal school-age children.
      These hypotheses addressed the theoretical relationships among resting cardiac
      vagal tone (using the Porges estimate of respiratory sinus arrhythmia, V),
      performance measures of sustained attention, and cardiac reactivity during
      sustained attention. Thirty-two fourth and fifth grade children performed a
      continuous performance task while their electrocardiograms were monitored.
      Children with higher resting levels of V performed better on the first 3-min
      block of the continuous performance task. Additionally, levels of V were
      significantly reduced across the blocks of the 9-min task for all children. No
      relationships were found between resting levels of V and change in either V or
      heart period during task performance. These findings support two of the three
      hypotheses proposed by Porges regarding individual differences in cardiac vagal
      tone and sustained attention.

PMID- 8146251
TI  - Event-related potentials indicate information extraction in a comparative
      judgement task.
AB  - Event-related potentials (ERPs) were recorded from normal subjects in a serial
      paired-comparison task with the spoken digits one to five. For each digit, the
      subject decided whether it was smaller or larger than the preceding one. We
      examined to what extent ERP components are associated with the probability
      information each digit provides with respect to the subsequent response. Shortest
      reaction time (RT) and highest accuracy was obtained for the two end terms one
      and five. The N1 and P2 components of the ERP were attenuated for the two end
      terms. Three late positivities were found: early P3, P3b, and slow wave. P3b
      increased in amplitude the more information the eliciting digit provided with
      respect to the response to the subsequent digit. Moreover, a negative correlation
      was found between the P3b amplitude associated with information extraction and
      the RTs to the subsequent digit. During comparative judgement, subjects process
      the relative position of a stimulus within a stimulus set to extract information
      about the probability of a forthcoming response, and this process is reflected in
      P3b amplitude.

PMID- 8146252
TI  - Parametric manipulations of auditory stimuli differentially affect P3 amplitude
      in schizophrenics and controls.
AB  - Schizophrenics show P3 amplitude reduction and topographic asymmetries. It is
      unclear whether the underlying cause of these deficits is primarily functional or
      structural. This study examined the effect of stimulus discriminability and task
      instruction on behavioral performance and P3 in schizophrenics and normal control
      subjects. Stimulus discriminability was manipulated by varying the overall
      loudness and pitch disparity of the two tones in an auditory oddball paradigm.
      Instructions emphasized either speed or accuracy of response. Instructions had no
      significant effects on reaction time, perceptual sensitivity, response bias, or
      P3. With increased discriminability, however, both groups improved in mean
      reaction time to targets and perceptual sensitivity. In controls, P3 became
      earlier and larger with increased stimulus discriminability and was consistently
      larger over left temporal areas than over right temporal areas. In
      schizophrenics, P3 latency was related to stimulus discriminability, but
      amplitude was not; P3 amplitude did not increase with improvement of perceptual
      sensitivity and reaction time. Unlike normal controls, schizophrenics had a P3
      asymmetry at temporal sites, with reduced left-sided voltages. The results are
      not consistent with a primarily functional cause of P3 aberrations in
      schizophrenia and are compatible with the hypothesis that P3 amplitude deficits
      in schizophrenia are related to underlying pathophysiology of temporal lobe
      generator sites.

PMID- 8146253
TI  - Resting EEG in first-episode and chronic schizophrenia.
AB  - We examined the frequency characteristics of the electroencephalogram (EEG) in
      102 schizophrenic patients (44 first-episode and 58 chronic patients) and 102
      normal comparison subjects. EEGs of schizophrenic patients had more delta (1-3
      Hz) and theta (3.125-8 Hz) activity and less alpha (8.125-13 Hz) activity than
      normal comparison subjects. There were no significant differences in the EEG
      frequency composition of first-episode and chronic patients. Because first
      episode and chronic patients were characterized by different disorder durations
      and treatment histories, the similarity of their EEGs suggests that EEG
      abnormalities are stable characteristics of schizophrenia and are not treatment
      related epiphenomena. A principal components analysis of EEG power bands
      identified an augmented low frequency-diminished alpha component and a beta
      component. Schizophrenic patients had significantly higher scores on the
      augmented low frequency-diminished alpha component than did normal comparison
      subjects, and there was no significant group difference in scores on the beta
      component. The findings of this investigation suggest that EEG abnormalities in
      schizophrenia reflect aspects of brain dysfunction.

PMID- 8146254
TI  - Autonomic space and psychophysiological response.
AB  - Contemporary findings reveal that autonomic control of dually innervated target
      organs cannot adequately be viewed as a continuum extending from parasympathetic
      to sympathetic dominance. Rather, a two-dimensional autonomic space, bounded by
      sympathetic and parasympathetic axes, is the minimal representation necessary to
      characterize the multiple modes of autonomic control. We have previously
      considered the theoretical implications of this view and have developed
      quantitative conceptual models of the formal properties of autonomic space and
      its translation into target organ effects. In the present paper, we further
      develop this perspective by an empirical instantiation of the quantitative
      autonomic space model for the control of cardiac chronotropy in the rat. We show
      that this model (a) provides a more comprehensive characterization of cardiac
      response than simple measures of end-organ state, (b) permits a parsing of the
      multiple transformations underlying psychophysiological responses, (c)
      illuminates and subsumes psychophysiological principles, such as the Law of
      Initial Values, (d) reveals an interpretive advantage of expressing cardiac
      chronotropy in heart period rather than heart rate, and (e) has fundamental
      implications for the direction and interpretation of a broad range of
      psychophysiological studies.

PMID- 8146255
TI  - Temporal stability of smooth-pursuit eye tracking in first-episode psychosis.
AB  - We evaluated the temporal stability of smooth-pursuit eye tracking in 38
      schizophrenic, 42 nonschizophrenic psychotic (bipolar, depressive, paranoid
      psychotic, and schizophreniform), and 49 normal subjects. Pursuit performance was
      evaluated on two testing occasions separated by approximately 9.5 months. Retest
      reliability coefficients of root mean square (RMS) error scores for schizophrenic
      and normal subjects were .68 and .57, respectively. The reliability coefficients
      of RMS error scores for the nonschizophrenic psychotic patients ranged from .44
      to .51. Level of psychological functioning was not significantly related to
      tracking performance, and most patients' pursuit performance remained stable
      despite changes in medication and clinical status. These results support the
      hypothesis that eye tracking dysfunction is a trait characteristic that can serve
      as a vulnerability indicator of schizophrenia.

PMID- 8146256
TI  - Probing the orienting response with startle modification and secondary reaction
      time.
AB  - Current models of orienting suggest a relationship between the orienting response
      and attentional processing. This relationship was examined using two independent
      probe techniques to index attentional processing: secondary reaction time and
      startle eyeblink modification. Twenty-eight college-age subjects received
      intermixed presentations of to-be-attended and to-be-ignored tones. Skin
      conductance orienting responses were obtained during a subset of the tones. Each
      of the remaining tones contained either a secondary reaction time probe at lead
      intervals of 150 or 2,000 ms or a startle eyeblink probe presented at lead
      intervals of 120 or 2,000 ms. In addition, reaction time and startle probes also
      were presented during selected intertone intervals, and responses to these
      stimuli served as the baselines from which to compare changes in reaction time
      and blink amplitude produced by the attended and ignored tones. The results
      revealed that, compared with the ignored tones, the attended tones were
      associated with larger skin conductance orienting responses, greater blink
      inhibition at the 120-ms lead interval, greater blink facilitation at the 2,000
      ms lead interval, and greater reaction time slowing at the 2,000-ms lead
      interval. Consistent with previous findings, the ignored tone was associated with
      greater reaction time slowing than was the attended tone at the 150-ms lead
      interval. The results support a relationship between elicitation of the skin
      conductance orienting response and attentional processes and suggest that the
      secondary reaction time and blink modification techniques may provide unique
      information regarding this relationship.

PMID- 8146257
TI  - Smooth pursuit in schizophrenia: abnormalities of open- and closed-loop
      responses.
AB  - A sample of 29 schizophrenia patients and 27 nonpsychiatric subjects were tested
      on measures of open- and closed-loop smooth-pursuit performance. Rashbass step
      ramps were used to measure pursuit latency and open-loop gain. Regular ramps were
      used to calculate frequency and amplitude of both catch-up saccades and square
      wave jerks, frequency of anticipatory saccades, and steady-state gain.
      Schizophrenia patients demonstrated lower open-loop gain than did nonpsychiatric
      subjects, an effect that was accentuated at faster target velocities. They also
      showed reduced steady-state gain, but only to 30 degrees/s right-moving targets.
      There was no evidence of saccadic abnormalities during smooth pursuit among the
      schizophrenia patients. These patients generated fewer square-wave jerks than did
      nonpsychiatric subjects for 10 degrees /s left-moving targets. These results
      suggest an abnormality of smooth-pursuit initiation among patients with
      schizophrenia.

PMID- 8146258
TI  - Conscious and nonconscious processes: an ERP index of an anticipatory response in
      a conditioning paradigm using visually masked stimuli.
AB  - This study investigates the nonconscious elicitation of a previously conditioned
      response by using a differential conditioning paradigm with visually masked
      affectively valent facial schematics. Electrodermal (skin conductance response
      [SCR] and brain (event-related potential [ERP]) activity were main dependent
      measures. Following a preconditioning phase in which subjects viewed energy
      masked pleasant and unpleasant facial schematics, conditioning with an aversive
      shock was established to unmasked presentations of an unpleasant face in a
      partial factorial design. A postconditioning phase of masked presentations, when
      compared with the preconditioning phase, revealed how the conditional effect
      within awareness might affect the same stimuli when presented outside awareness.
      An adaptive staircase technique was used to establish individual threshold
      levels, which represented a methodological advance over procedures typically used
      in visual masking research. The results revealed that responses to the CS+
      (unpleasant face) changed significantly in predicted directions from
      preconditioning to postconditioning phase when compared with responses to the CS-
      (pleasant face). The SCR results systematically replicated recent Ohman, Dimberg,
      and Esteves (1988) findings, with the pattern of responses resembling a
      resistance to extinction effect. A new finding emerged for the brain responses.
      For the CS+, distinct slow wave activity occurred just before the point at which
      the shock had been delivered in the conditioning phase; no such activity was
      found for the CS-. This slow wave activity is similar to what has been described
      by others as an expectancy wave. The results indicate that an anticipatory
      process, as indexed by different physiological systems, can be elicited entirely
      outside awareness. Implications are discussed in regard to the nature of
      conscious and nonconscious processes.

PMID- 8146259
TI  - [Chronic grief after spontaneous abortion: results of a longitudinal study after
      13 months].
AB  - Presented are follow-up results on coping with spontaneous abortion. Although the
      majority of women feel that this is a significant negative life event, their
      grief gradually decreases within 7 to 13 months. Compared to population standards
      they are neither depressed nor do they suffer from increased physical complaints.
      A subgroup of women is identified with chronic ("pathological") grief based on
      increased or rising levels of grief (PGS), depression (SCL-90) and physical
      complaints (BL). Independently from a following pregnancy these women (about 20%)
      report a high importance of their abortion, painful feelings in seeing pregnant
      women and babies and fears of another abortion even after 13 months. Scores
      immediately after the abortion permit a good discrimination of patients with
      chronic grief and uncomplicated course: Patients who later develop chronic grief
      report a high level of negative feelings during the pregnancy leading to the
      loss, extensive preparations for the expected baby, an unsettled vocational and
      family situation and intensive strains and despair immediately thereafter.
      Conditions and ways of grieving with this specific loss are discussed.

PMID- 8146260
TI  - [Body image of anorexic girls, their mothers and sisters: a controlled study].
AB  - Body image disturbance is a main diagnostic criterion for anorexia nervosa.
      However, its transmission in families has never been studied empirically. Our
      study compared the body experience of a consecutive series of 29 adolescent
      anorexics at initial assessment (DSM-III-R, mean age 14.4 years), their mothers
      (n = 29) and 9 sisters with a control group of 29 healthy girls (matched in age
      and education), their mothers (n = 29) and 10 sisters, using the Body Experience
      Questionnaire (Strauss u. Appelt 1983). Within-group comparison revealed no
      significant differences in the control group. Although anorexics showed a more
      negative body experience than their mothers and sisters, the between-group
      comparisons revealed no significant differences to healthy controls, neither in
      cases nor in their sisters. Surprisingly, mothers of anorexics reported a
      significantly more positive body experience than control mothers. Whereas in
      patients and their mothers a correlation of insecurity was found, the control
      mother-daughter-pairs revealed a correlation of attractiveness. In the
      transmission of body experience amongst female family members negative aspects
      seem to play a major role between mothers and their anorexic daughters, whereas
      positive aspects correlate significantly in healthy mothers and daughters;
      mothers of anorexics may communicate specific negative aspects of body experience
      to anorexic daughters or anorexics might be more susceptible to such messages. If
      further studies confirm our results, this should have consequences for treatment.

PMID- 8146261
TI  - [Clinical contribution to female identity crisis after loss of the uterus].
AB  - In the last decades a hysterectomy-boom is described both in Anglosaxon and in
      German medical literature. This can in no way be correlated with a increase of
      the pathologic-anatomic, respectively patho-physiologic processes of this organ.
      By means of two examples of analytic psychotherapy, it can be shown that the
      libidinous filling of the uterus in the psychic representation in the physic
      appearance of the woman is not congruent with the physiologic hierarchy of female
      sexual organs in medical science. According to a more or less happy partnership
      and the postoperative feed-back of the concerned partner, the loss of the uterus
      will produce, even when the reproduction phase is over, variously sensible
      disturbances of the narcissistic regulation of self-evaluation. These may be
      irreparable in aggravating cases. As causes of too frequent hysterectomies
      correspond auto-destructive impulsives of the concerned women with regressed
      aggressive impulses in the persons of gynecologic operators.

PMID- 8146262
TI  - [Body image of the male athlete. A study of the psychological health of wrestlers
      and rowers of the lower weight class].
AB  - The present study reports findings concerning the body-experience of male
      athletes. 25 wrestlers and 59 rowers in the lower weight categories were
      investigated using the questionnaire for evaluation of body-experience
      "Fragebogen zur Beurteilung des eigenen Korpers--FBK" (Strauss u. Appelt, 1983).
      Due to nature of their sports, these men are particularly subject to a constant
      pressure to maintain a low body weight. In 31% of the subjects the FBK profiles
      were indicative of disturbances of body-image and body-experience. This subgroup
      also demonstrated multiple pathologically elevated scores in the personality
      questionnaire "Freiburger Personlichkeitsinventar" (Fahrenberger et al. 1984) and
      the Eating-Disorder-Inventory (Garner et al. 1983). Low-weight wrestlers and
      rowers should be considered a high-risk male population for body-image
      disturbances and other psychological disorders. The casual relationship between
      the specific sport and the development of an body-image disorder is discussed.

PMID- 8146263
TI  - [Self concept and ideal self concept in the Giessen Test of students in East and
      West Germany].
AB  - We report about a comparative study on epidemiological and psychological
      variables in two samples of students in the German universities of Gottingen
      (West Germany) and Halle (East Germany) from April 1991 (n = 438). We expected
      specific differences in the answers due to the differing socialization and actual
      life stress. In this paper we present results on self images and ideal self
      images, measured with the Giessen-Test. East- and West German students in general
      have similar self images in the GT-scales. There are significant differences
      between the study fields, suggesting a higher correlation between personality
      variables and subject of studies than between personality and country. In some
      gender specific items women in Halle show a tendency towards a more traditional
      gender role concept (less competition, importance of attractiveness). Men in East
      Germany compared to the western students emphasized freedom from anxiety and
      walling off. The ideal self image in the west is characterized by wishes for more
      sociability and less competition. In the east there is a tendency towards wishes
      for autonomy and control. The significant differences in gender specific items
      and in the ideal self image are discussed under aspects of socialization and
      actual stressors.

PMID- 8146264
TI  - [Characteristics of young suicide attempters and their importance for helpers].
AB  - 66 suicide attempters were interviewed with the European Parasuicide Study
      Interview Schedule (EPSIS) and characteristics of persons under the age of 26
      were compared with those over 26.82% of the young suicide attempters gave
      interpersonal conflicts as reasons for their suicide attempts while most older
      persons gave psychiatric disorders as reasons. The younger group also had
      significantly lower scores on the Beck Depression Inventory and the Hopelessness
      Scale. While younger suicide attempters rarely had sought help from their GP
      within the month preceding the attempt one third of the older group had done so.
      It is concluded that in order to understand the reasons why people attempt
      suicide a differential approach combining the concept of crisis as well as the
      concept of illness is needed. Helpers should know that young suicide attempters
      rarely show signs of clear psychiatric disorder but usually attempt suicide
      because they are unable to cope with interpersonal conflicts.

PMID- 8146265
TI  - [Psychotherapeutic counseling and treatment of students within the scope of a
      psychotherapy counseling center].
AB  - The field of psychotherapeutic counseling in germany is rather heterogeneous and
      scientifically scarcely investigated. As an example the author describes the
      organisation and methods of a psychotherapeutic counseling service for students.
      Statistical material of the kind of complaints and disorders is given and first
      results of an evaluation study are reported.

PMID- 8146266
TI  - [Epidemiologic findings on the spontaneous long-term course of psychogenic
      disease over 10 years].
AB  - 207 individuals were selected from a random sample of the adult urban population
      of Mannheim according to the criterion of medium psychogenic impairment (high
      risk population) and investigated three times between 1979 and 1991 with regard
      to prevalence and severity of psychogenic disorders. In contrast to clinical
      investigations, the present data render statements on the spontaneous course of
      psychogenic disorders in the general population. The existing psychogenic
      impairment was determined by means of various operationalizations
      (symptomatology, ICD-diagnoses, severity of impairment). The available data
      indicate a high stability of psychogenic impairment in the spontaneous course.
      Group statistically the severity of impairment even increases in the long term
      course. However, different subtypes of course in the investigated high-risk
      population can be identified by a cluster analysis.

PMID- 8146267
TI  - [The Ulm databank].
AB  - Since 1968 one of our major research efforts consists in establishing a
      methodology for performing psychoanalytic process research. Within this frame
      tape-recording of psychoanalytic long-term treatments constituted an essential
      methodical step inevitably leading to the production of a large collection of
      verbatim transcripts. We gradually and inadvertently realized the need for a
      major computerized databank to assist our own research. With support of the
      German Research Foundation we started in 1980 with the development of the Ulm
      Textbank Management System. While realizing the system it became obvious that
      such a databank would serve as well other researchers involved in process
      research when analyzing verbatim material. The final shape of the systems thus
      was strongly influenced by the orientation towards a variety of users and
      methodological approaches. Meanwhile this task is completed and the Ulm Textbank,
      as it is known, is available as a new unique tool for psychotherapy research.

PMID- 8146268
TI  - [Transition from adolescence to young adulthood. Empirical comparative studies of
      the psychosocial development and problems of psychiatric patients and healthy
      control probands].
AB  - The passage from adolescence to young adulthood is characterized by a series of
      decisive developmental tasks. The significance of the adaptational patterns
      established in these years derives from their long-lasting influences on the
      psychosocial development during adult life. The psychosocial development of
      psychiatrically ill and healthy young adults was compared in respect to self
      image (Offer), identity status (Adams) and level of ego functionality
      (Loevinger). Patients showed serious deficits in general psychosocial adaptation
      (self image) especially pronounced in the areas of private personality
      development and family life. They were significantly less able to respect a
      developmental logic of exploration and commitment in the formation of identity.
      And their level of ego functions was primarily unmature, preconformist. There
      were important differences in the adaptational patterns of patient subgroups
      indicating a remarkably unfavourable psychosocial development of the nonpsychotic
      patients. Subjective (self image) and objective criteria (premorbid adaptation,
      actual psychosocial competence) of psychosocial development corresponded well.

PMID- 8146269
TI  - Fluorescence in situ hybridization in cancer and radiation biology.
AB  - This review describes molecular cytogenetic approaches to genetic analysis
      including fluorescence in situ hybridization, primed in situ labeling and
      comparative genomic hybridization. It also summarizes the applications of this
      technology to physical mapping, cancer diagnosis and prognostication and in
      radiation biology.

PMID- 8146270
TI  - Noninvolvement of the X chromosome in radiation-induced chromosome translocations
      in the human lymphoblastoid cell line TK6.
AB  - Fluorescence in situ hybridization procedures were used to examine the influence
      of chromosome locus on the frequency and type of chromosome aberrations induced
      by 60Co gamma rays in the human lymphoblastoid cell line TK6. Aberrations
      involving the X chromosome were compared to those involving the similarly sized
      autosome chromosome 7. When corrected for DNA content, acentric fragments were
      induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases
      in chromosomal interchanges involving chromosome 7 were noted and the frequencies
      of balanced translocations and dicentrics produced were approximately equal.
      Chromosome interchanges involving the X chromosome were rare and showed no
      apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive
      to the induction of chromosome breaks, the X chromosome is much less likely to
      interact with autosomes than chromosome 7. The noninvolvement of the X chromosome
      in translocations with autosomes may reflect a more peripheral and separate
      location for the X chromosome in the mammalian nucleus.

PMID- 8146271
TI  - Yield of single-strand breaks due to attack on DNA by scavenger-derived radicals.
AB  - We have measured the yield of single-strand breaks (SSBs) in plasmid DNA after
      137Cs gamma irradiation, in the presence of dimethyl sulfoxide (DMSO). In the
      presence of oxygen, the formation of SSBs is due to hydroxyl radical attack. As
      the DMSO concentration is increased from 10(-4) mol dm-3 to 1 mol dm-3, the SSB
      yield in the presence and absence of oxygen decreases by over 100-fold and less
      than 10-fold, respectively. From the DMSO and DNA concentration dependencies of
      the SSB yield in the absence of oxygen, the second-order rate constant for the
      reaction of the methyl radical (derived from DMSO) and DNA can be estimated as k2
      = 8.8 x 10(4) dm3 mol-1 s-1. Several other scavengers were compared with DMSO
      under anoxia. Radicals derived from isopropyl alcohol and glycerol also caused
      SSB formation in DNA, while those from 2-deoxyribose, thymine, 1,3
      dimethylthymine and 1,3-dimethyluracil did not. In the case of the scavenger tert
      butyl alcohol, it is unclear whether the hydrogen atom (H.) or an organic radical
      is responsible for the higher SSB yield under anoxic conditions.

PMID- 8146272
TI  - ESR and ENDOR study of single crystals of deoxyadenosine monohydrate X-irradiated
      at 10 K.
AB  - Five free radicals have been detected by detailed ESR/ENDOR experiments on single
      crystals of deoxyadenosine monohydrate (AdRm), X-irradiated and observed at 10 K.
      In a previous study of adenosine (Radiat. Res. 117, 367-378, 1989), only the
      anion (protonated at N3) and the cation (deprotonated at the exocyclic NH2) were
      detected at 10 K. In AdRm, Radical R1 is the N3-protonated anion, similar to that
      observed previously in adenosine. Radical R3 is a C5' hydroxyalkyl radical formed
      by net H-abstraction from C5'. A second sugar radical is formed by net C1' H
      abstraction. Two other base radicals observed in AdRm at 10 K are the C2 and C8 H
      addition radicals. The C2 H-addition radical (Radical R5) exhibits inequivalent
      methylene hydrogen couplings of 5.43 and 3.29 mT, while in the C8 H-addition
      radical (Radical R6) the couplings are somewhat more equivalent (3.63 and 4.17
      mT). No link between RAdical R1 and the H-addition radicals has been observed.
      The reduced base appears to protonate rapidly even at 10 K, while at the same
      time both H-addition radicals are clearly present. On warming, Radical R1 appears
      to decay at about 80 K with no apparent successor. Although no base cation was
      stabilized in AdRm at 10 K, it is interesting to note that Radicals R3 and R4
      could both be formed as the result of deprotonation of primary oxidation
      products.

PMID- 8146273
TI  - Detection of retinoblastoma gene deletions in spontaneous and radiation-induced
      mouse lung adenocarcinomas by polymerase chain reaction.
AB  - A polymerase chain reaction (PCR) technique has been developed to detect
      deletions in the mouse retinoblastoma gene using histological sections from
      radiation-induced and spontaneous tumors as the DNA source. Six mouse Rb gene
      exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The
      absence of any of these fragments relative to control PCR products on a Southern
      blot indicated a deletion of that portion of the mouse Rb gene. Tumors chosen for
      analysis were lung adenocarcinomas that were judged to be the cause of death.
      Spontaneous tumors as well as those from irradiated mice (5.69 Gy 60Co gamma rays
      or 0.6 Gy JANUS neutrons, which have been found to have approximately equal
      radiobiological effectiveness) were analyzed for mouse Rb deletions. Tumors in 6
      neutron-irradiated mice had no mouse Rb deletions. However, 1 of 6 tumors from
      gamma-irradiated mice (17%) and 6 of 18 spontaneous tumors from unirradiated mice
      (33%) showed a deletion in one or both mouse Rb alleles. All deletions detected
      were in the 5' region of the mouse Rb gene.

PMID- 8146274
TI  - High levels of stable p53 protein and the expression of c-myc in cultured human
      epithelial tissue after cobalt-60 irradiation.
AB  - When explants of human uroepithelium or esophageal epithelium are exposed to
      acute doses of radiation (cobalt-60), the cells which grow out to form the
      primary cultures show a number of abnormal features. These include the
      development of characteristic nonsenescent foci. These foci have previously been
      shown to be c-myc positive and to have an abnormal, tumor-like ultrastructure.
      Expression of c-myc and the level of stable p53 proteins have now been examined
      in these cultures 2 weeks after irradiation. Both proteins occurred in dividing
      cells at the growing edge of the explant and in the foci. The expression of c-myc
      appeared to be correlated with growth. As expected, variation between individual
      cultures of normal human cells were noted in the expression of stable p53
      protein. Most control uroepithelial cell cultures were negative, but a small
      cohort showed a wide range of values. The control cultures from the esophageal
      tissues had high expression of p53, and this decreased marginally after
      irradiation. Cells positive for p53 were always in cycle and were usually
      positive for c-myc as well. It would appear from these results that the
      expression of c-myc and the stable form of the p53 protein occur in irradiated
      primary cultures of normal human cells both in foci which also express a number
      of abnormalities and in "edge" cells which are dividing. Cultures of unirradiated
      cells from esophagus and a small number of uroepithelial samples had high levels
      of p53. Possible reasons for this are discussed.

PMID- 8146275
TI  - The effect of postirradiation holding at 22 degrees C on the repair of sublethal,
      potentially lethal and potentially neoplastic transforming damage in gamma
      irradiated HeLa x skin fibroblast human hybrid cells.
AB  - The effect of postirradiation holding at 22 degrees C on cell growth, progression
      of cells through the cell cycle, and the repair of sublethal, potentially lethal
      and potentially neoplastic transforming damage in gamma-irradiated HeLa x skin
      fibroblast human hybrid cells has been examined. Cell growth and cell cycle
      progression were essentially stopped at this reduced temperature. Cell survival
      was dramatically reduced by holding confluent cultures for 6 h at 22 degrees C,
      as opposed to 37 degrees C, after 7.5 Gy gamma radiation delivered at a rate of 2
      Gy/min. Return of the cells to 37 degrees C for 6 h after holding at 22 degrees C
      did not result in increased survival. A similar effect was obtained when the
      cells were held at 22 degrees C between split-dose irradiation of log-phase
      cultures where no increase in survival was observed over a split-dose interval of
      4 h. In this case a partial increase in survival was observed upon returning the
      cells to 37 degrees C for 3 h after holding at 22 degrees C for the first 3 h of
      the split-dose interval. Neoplastic transformation frequency was not enhanced by
      holding confluent cultures for 6 h at 22 degrees C after 7.5 Gy gamma radiation.
      This is consistent with previous observations that misrepair of potentially
      neoplastic transforming damage already occurs at 37 degrees C. The overall
      results are interpreted in terms of the reduced temperature favoring misrepair,
      rather than inhibition of repair, of sublethal, potentially lethal and
      potentially transforming radiation damage.

PMID- 8146276
TI  - Quantifying the frequency of radiogenic thyroid cancer per clonogenic cell in
      vivo.
AB  - We used quantitative cell transplantation to evaluate the frequencies of the
      formation of radiogenic thyroid cancer per clonogenic rat thyroid epithelial cell
      in vivo. Irradiation of thyroid cells with 5 Gy 137Cs gamma rays before
      transplantation significantly increased the incidence of thyroid carcinoma
      formation in such grafts compared to similar grafts of unirradiated thyroid
      cells. We calculated the frequencies of radiogenic cancer by subtracting cancer
      incidences in unirradiated groups from incidences in irradiated groups and
      dividing by the number of clonogens grafted. The highest observed frequencies of
      radiogenic thyroid cancer so calculated were 0.141 and 0.046 cancers per
      surviving irradiated clonogenic cell. These cancer frequencies occurred in grafts
      containing averages of three and ten clonogens per site, respectively, and
      represent one cancer per approximately 7 and approximately 22 irradiated
      clonogens. We conclude that the highest observed frequencies of radiogenic cancer
      are likely to be the best estimates of the "real" frequency per irradiated
      clonogen in that virtually all the methodological sources of inaccuracy tend to
      decrease the observed frequency compared to the "real" frequency. Radiogenic
      initiation of cancer is thus a highly common cellular event among surviving
      irradiated clonogenic thyroid cells. To examine the role of endocrine-mediated
      tumor promotion on the expression of radiogenic cancer, we attenuated the
      intensity of thyrotropin (TSH)-mediated tumor promotion in some groups of
      recipient animals. We found that the incidence rates for radiation-associated
      cancer were significantly higher in rats with higher serum TSH levels compared to
      rats with lower TSH levels. We conclude from these data that (1) radiogenic
      thyroid cancer occurs with a high frequency and (2) chronic TSH stimulation
      accelerates progression of radiogenic neoplasms to overt carcinomas and promotes
      development of later-arising carcinomas in grafts of unirradiated thyroid
      clonogens.

PMID- 8146277
TI  - Comparison of thermoradiosensitization in two human melanoma cell lines and one
      fibroblast cell line by concurrent mild hyperthermia and low-dose-rate
      irradiation.
AB  - Two human melanoma cell lines, one radioresistant (SK-MEL-3) and one
      radiosensitive (HT-144), and a normal human fibroblast line (AG1522) were
      evaluated for thermoradiosensitization of low-dose-rate irradiation by concurrent
      mild hyperthermia (39-41 degrees C). None of the cell lines expressed chronic
      thermotolerance during heating at 39-41 degrees C. The SK-MEL-3 cells were the
      most heat sensitive, while AG1522 and HT-144 cells had the same sensitivity at 39
      and 40 degrees C but HT-144 cells were more sensitive at 41 degrees C. All cell
      lines expressed thermal enhancement of radiosensitivity with heating during
      irradiation which increased with heating temperature. The SK-MEL-3 cells, which
      were the most resistant to radiation and demonstrated the greatest repair of
      sublethal damage (SLD) during low-dose-rate irradiation, had the greatest thermal
      enhancement of radiosensitivity, while the HT144 cells, which were the most
      sensitive and expressed little repair of SLD during low-dose-rate irradiation,
      had the smallest thermal enhancement of radiosensitivity. These data show that
      concurrent mild hyperthermia during low-dose-rate irradiation may be most
      efficacious in radiation-resistant tumor cells which express resistance through
      an enhanced capacity for repair of SLD.

PMID- 8146278
TI  - A method for computing random chord length distributions in geometrical objects.
AB  - A method is described that uses a Monte Carlo approach for computing the
      distribution of random chord lengths in objects traversed by rays originating
      uniformly in space (mu-randomness). The resulting distributions converge
      identically to the analytical solutions for a sphere and satisfy the Cauchy
      relationship for mean chord lengths in circular cylinders. The method can easily
      be applied to geometrical shapes that are not convex such as the region between
      nested cylinders to simulate the sensitive volume of a detector. Comparisons with
      other computational methods are presented.

PMID- 8146280
TI  - Bone sarcoma characteristics and distribution in beagles injected with radium
      226.
AB  - A total of 155 primary bone sarcomas were found in 131 of the 246 beagles
      injected with 226Ra and 5 primary bone sarcomas were found in 4 of the 158
      unexposed controls. Of these 155 bone sarcomas, 146 (94%) were osteosarcomas and
      9 were non-osteosarcomas. An additional 31 primary bone sarcomas (28
      osteosarcomas) developed in 44 dogs terminated from the main study because of
      limb amputation for bone sarcoma. Non-osteosarcomas predominated in both the
      controls and the second lowest of six logarithmically increasing dose levels
      (there were no bone sarcomas in the lowest dose group). Osteosarcomas
      predominated at the higher dose levels, and incidence tended to increase as dose
      increased. The 146 osteosarcomas were distributed quite evenly between males and
      females (72:74). Of the 9 non-osteosarcomas, 6 occurred in males and 3 in
      females. The ratio of bone sarcomas of the appendicular skeleton to those in the
      axial skeleton was 110:45, with osteosarcomas occurring more often in the
      appendicular skeleton (108:38). Cases of multiple primary bone sarcomas in dogs
      injected with 226Ra were found only in the four highest dose groups. Amputations
      were performed on 44 of the 96 dogs (94 injected and 2 unexposed) that developed
      appendicular bone sarcomas. A statistical study of the distribution of bone
      sarcomas among 16 separate bone groups showed a statistically significant
      correlation to cancellous skeletal surface, but the variability among bone groups
      was too large for this relationship to be of real predictive value. It is
      postulated that the distribution of bone sarcomas reflects primarily the relative
      cell division rates in the bone groups and secondarily the radiation dose
      distribution, with the highest occurrence of bone sarcoma in the humeri, pelvis,
      femora and tibiae/fibular tarsal, and no occurrence in the coccygeal vertebrae,
      sternum, forepaws or hindpaws.

PMID- 8146279
TI  - Relative biological effectiveness of alpha-particle emitters in vivo at low
      doses.
AB  - The therapeutic potential of radionuclides that emit alpha particles, as well as
      their associated health hazards, have attracted considerable attention. The 224Ra
      daughters 212Pb and 212Bi, by virtue of their radiation properties which involve
      emission of alpha and beta particles in their decay to stable 208Pb, have been
      proposed as candidates for radioimmunotherapy. Using mouse testes as the
      experimental model and testicular spermhead survival as the biological end point,
      the present work examines the radiotoxicity of 212Pb and its daughters. When
      212Pb, in equilibrium with its daughters 212Bi, 212Po and 208Tl, was administered
      directly into the testis, the dose required to achieve 37% survival (D37) was
      0.143 +/- 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7
      when compared to the D37 for acute external 120 kVp X rays. This datum, in
      conjunction with our earlier results for 210Po, was used to obtain an RBE-LET
      relationship for alpha particles emitted by tissue-incorporated radionuclides:
      RBE alpha = 4.8 - 6.1 x 10(-2) LET + 1.0 x 10(-3) LET2. Similarly, the dependence
      of RBE on alpha-particle energy E alpha was given by RBE alpha = 22 E(-0.73)
      alpha. These relationships, based on in vivo experimental data, may be valuable
      in predicting biological effects of alpha-particle emitters.

PMID- 8146281
TI  - Southern blot and polymerase chain reaction exon analyses of HPRT- mutations
      induced by radon and radon progeny.
AB  - A linear dose response was observed for radon-induced mutations at the CHO-hprt
      locus with an induction frequency of 1.4 x 10(-4) mutants per viable cell per
      gray. Mutants isolated after two levels of radon exposure were evaluated using
      Southern blot techniques and polymerase chain reaction (PCR) exon amplification.
      No significant differences in mutational spectra were detected at these two
      exposure levels. Of 52 radon-induced mutations, 48% sustained a gene deletion,
      23% underwent a rearrangement of the banding patterns or loss of one or more
      exons, and 29% showed no change from the parental line. These mutants were
      compared with mutants produced after X irradiation (3 Gy) and with spontaneous
      mutants from untreated cells. The spectra of mutation types in cells treated with
      radon and X rays were not significantly different. In contrast, 31 spontaneous
      mutations exhibited a low percentage of gene deletion events (16%); most
      spontaneous mutants showed no change (74%); the remaining 10% were classified as
      alterations. In conclusion, the principal lesion seen at the CHO-hprt locus after
      radiation exposure is gene deletion, while the predominant class of spontaneous
      mutations is composed of smaller events not detectable by Southern blot or PCR
      exon analysis.

PMID- 8146282
TI  - Alpha particles are extremely damaging to developing hemopoiesis compared to
      gamma irradiation.
AB  - Estimates of risk of stochastic effects from contamination with alpha-particle
      emitting radionuclides are based on equivalent doses which take into account the
      RBE of the high-LET radiation. ICRP has recommended a dose-weighting factor, wR,
      of 20 for alpha-particle radiation. It is assumed that the RBEs for deterministic
      effects are considerably less than those for stochastic effects. However, the
      offspring of mice injected with 30 Bq g-1 239Pu at 13 days gestation develop a
      persistent deficit in hemopoietic stem cells which is primarily the result of
      damage to their regulatory microenvironment. Their spatial distribution in the
      marrow is also perturbed, and recent observations on those mice suggested a
      considerably higher factor than 20. To define a more realistic RBE for
      hemopoiesis, the effects of external gamma irradiation during the fetal
      development period have been compared directly with those of 239Pu incorporated
      via placental transfer on the development of hemopoietic tissue. Pregnant mice
      were irradiated with 60Co gamma rays (a) continuously from day 13 of gestation to
      birth at 0.15 or 0.6 Gy/day; (b) six repeated acute doses (0.6 Gy/min) at 0.1 or
      0.3 Gy from day 13 of gestation; (c) one acute dose of 0.6 or 1.8 Gy on day 15 of
      gestation. The spatial distribution of hemopoietic stem cells in 8-week-old
      offspring was then determined and compared to that resulting from alpha-particle
      irradiation. In each case, the higher dose was required to match the results for
      alpha particles, suggesting an RBE for developing hemopoiesis of 250-360 compared
      to a continuous gamma-ray dose and a rather lower value of 130-180 compared to a
      single acute dose of gamma rays. This contrasts greatly to values for direct
      irradiation of the stem cells but argues that the effective RBE, measured for
      long-term effects in vivo, is the more realistic. It is concluded that an all
      embracing factor can be grossly misleading in the specification of protection
      guidelines and can greatly underestimate the risks of exposure to alpha
      particles.

PMID- 8146283
TI  - Electron migration along 5-bromouracil-substituted DNA irradiated in solution and
      in cells.
AB  - Solvated electrons generated in aqueous solution after exposure to ionizing
      radiation can be scavenged by DNA and then transferred along the DNA molecule.
      This mechanism of charge transfer provides an opportunity for radiation damage to
      be targeted to certain regions in the DNA molecule and is a mechanism by which
      single-strand breaks contribute to locally multiply damaged sites to enhance cell
      lethality. Experiments were performed in which different amounts of 5-bromouracil
      (5-BrU) were substituted for thymine in Escherichia coli DNA. The amount of
      bromide released was assayed after quantitative reaction of radiation-induced
      solvated electrons with 5-BrU in DNA samples irradiated in solution and
      irradiated in the cellular environment. By varying the amount of 5-BrU
      incorporated in the DNA, the average distance between 5-BrU molecules was
      systematically changed and, because the number of 5-BrU/electron reactions was
      monitored by the amount of bromine released, the maximum average electron
      migration distance along the 5-BrU DNA could be estimated. Using this approach,
      the maximum average electron migration distance in aqueous solutions of 5-BrU DNA
      was about 6.5 to 10 base distances in nonhybrid 5-BrU DNA (assuming only
      intrastrand migration). Similar methods revealed charge migration in 5-BrU DNA
      incorporated into E. coli, and the maximum average migration distance was about 5
      to 6 base distances (assuming only intrastrand migration). Only 11-16% of the
      electrons produced during radiolysis were scavenged by 5-BrU DNA in aqueous
      solution, and only 1% resulted in the release of bromide from 5-BrU-DNA inside E.
      coli.

PMID- 8146284
TI  - Vitamins as radioprotectors in vivo. I. Protection by vitamin C against internal
      radionuclides in mouse testes: implications to the mechanism of damage caused by
      the Auger effect.
AB  - The potential of vitamin C, an antioxidant, to protect the radiosensitive
      spermatogonial cells in mouse testes against the effects of chronic irradiation
      by radionuclides incorporated into tissue was investigated. Interestingly, when
      injected intratesticularly, a small and nontoxic amount of vitamin C (1.5
      microgram in 3 microliters saline) protected the spermatogonia against the damage
      associated with high-LET radiation caused by Auger electrons from similarly
      administered 5-(125I)-iodo-2'-deoxyuridine (125IdU). A dose modification factor
      (DMF) of 2.3 was obtained. In contrast, no protection was observed when 210Po, an
      alpha-particle emitter, was administered similarly. These findings suggest that
      the mechanism of action of the Auger effect is of an indirect nature, which is in
      contrast to the direct action generally believed to be responsible for biological
      damage caused by high-LET radiations.

PMID- 8146285
TI  - Misoprostol in the intestinal lumen protects against radiation injury of the
      mucosa of the small bowel.
AB  - Systemically administered misoprostol, a PGE1 analog, has been shown to be an
      intestinal radioprotector. The purpose of this study was to determine if
      administration of misoprostol into the intestinal lumen can also reduce the
      severity of acute radiation enteritis. The rat small bowel was operatively
      exteriorized and segmented by means of suture ties. The remainder of the
      intestine and the rat were shielded in a lead box. Misoprostol was introduced
      into the lumen in various doses. After 30 min exposure to misoprostol, the
      isolated, exteriorized, segmented bowel was subjected to 11 Gy X irradiation.
      Five days later the animals were sacrificed and the intestines harvested for
      evaluation. Surviving crypt numbers per circumference and mucosal height were the
      criteria used for quantification of damage. Mucosa exposed to misoprostol at the
      time of radiation delivery showed significantly increased crypt numbers and
      mucosal height compared to adjacent saline-filled intestine.

PMID- 8146286
TI  - Dose.
AB  - The universal use of dose as a normalizing parameter in radiobiology is based
      entirely on the availability of measuring instruments. It is a poor basis for
      predicting or understanding the relationship between an irradiation and the
      resulting end point. Energy deposited is not the cause of an interaction. It is a
      secondary effect. The interaction is best described by fluence and cross section.
      Energy deposited depends principally upon inelastic collision cross sections for
      the interaction of electrons with molecules. Especially for heavy-ion
      bombardments, for high-LET radiations, inelastic electron collision cross
      sections relate only remotely to the observed end points of interest. When dose
      is used to describe effects observed with radiations of different "quality,"
      response predictions can be very wide of the mark. One way to describe such a
      relationship is through the relative biological effectiveness (RBE). If we
      consider the RBE to be a correction factor to be applied to a prediction of
      response based on dose, we find that its values range from 0.01 to infinity. It
      is apparent that in general dose is a useless predictor of response, except in
      narrowly defined circumstances.

PMID- 8146287
TI  - Comments on "Radiation dose-fractionation and dose-rate relationships for long
      term repopulating hemopoietic stem cells in a murine bone marrow transplant
      model" by R. van Os, H. Thames, A. W. T. Konings and J. D. Down (Radiat. Res.
      136, 118-125, 1993)

PMID- 8146288
TI  - EPR dosimetry of cortical bone and tooth enamel irradiated with X and gamma rays:
      study of energy dependence.
AB  - Previous investigators have reported that the radiation-induced EPR signal
      intensity in compact or cortical bone increases up to a factor of two with
      decreasing photon energy for a given absorbed dose. If the EPR signal intensity
      was dependent on energy, it could limit the application of EPR spectrometry and
      the additive reirradiation method to obtain dose estimates. We have recently
      shown that errors in the assumptions governing conversion of measured exposure to
      absorbed dose can lead to similar "apparent" energy-dependence results. We
      hypothesized that these previous results were due to errors in the estimated dose
      in bone, rather than the effects of energy dependence per se. To test this
      hypothesis we studied human adult cortical bone from male and female donors
      ranging in age from 23 to 95 years, and bovine tooth enamel, using 34 and 138 keV
      average energy X-ray beams and 137Cs (662 keV) and 60Co (1250 keV) gamma rays. In
      a femur from a 47-year-old male (subject 1), there was a difference of borderline
      significance at the alpha = 0.05 level in the mean radiation-induced
      hydroxyapatite signal intensities as a function of photon energy. No other
      statistically significant differences in EPR signal intensity as a function of
      photon energy were observed in this subject, or in the tibia from a 23-year-old
      male (subject 2) and the femur from a 75-year-old female (subject 3). However,
      there was a trend toward a decrease (12-15%) in signal intensity at the lowest
      energy compared with the highest energy in subjects 1 and 3. Further analysis of
      the data from subject 1 revealed that this trend, which is in the opposite
      direction of previous reports but is consistent with theory, is statistically
      significant. There were no effects of energy dependence in the tooth samples.

PMID- 8146289
TI  - Radiation-induced changes in the kinetics of glomerular and tubular cells in the
      pig kidney.
AB  - Both kidneys of 13 mature female Large White pigs were irradiated with a single
      dose of 9.8 Gy 60Co gamma rays. The pigs were killed serially between 2 to 24
      weeks after irradiation. One hour prior to sacrifice bromodeoxyuridine (BrdU)
      (500 mg/pig) was injected intravenously. At postmortem the kidneys were removed
      and tissue was taken to prepare cell suspensions. The labeling index (LI) of
      these suspensions was determined using flow cytometry. In vivo BrdU incorporation
      in tubular and glomerular cells was determined immunohistochemically. The
      kinetics of glomerular and tubular cells was evaluated by counting the number of
      labeled cells/glomerulus and the number of labeled tubular cells/field of view.
      An average of 1200 glomeruli and 1500 fields of view/time were counted. Similar
      analyses were performed on renal tissue from unirradiated control animals. Flow
      cytometry revealed rapid and significant increases in the LI of kidney cells; 2
      weeks after irradiation the LI increased from a control value of 0.18 +/- 0.01 to
      1.23 +/- 0.22% (P < 0.001). By 4 weeks the maximal value of 2.45 +/- 0.36% was
      seen; the LI then declined progressively but at 24 weeks after irradiation still
      remained significantly above control values (P < 0.001). A similar pattern of
      response was determined by counting the labeled glomerular and tubular cells
      identified immunohistochemically. However, the increase in labeled glomerular
      cells occurred 2 weeks after irradiation, whereas that for the tubules occurred 4
      weeks after irradiation. These findings indicate that irradiation of the kidney,
      classically regarded as a "late-responding" organ, is associated with rapid and
      significant changes in the kinetics of both tubular and glomerular cells.

PMID- 8146290
TI  - Stimulation of respiration in rat thymocytes induced by ionizing radiation.
AB  - The effect of X irradiation on the respiration of rat thymocytes was studied. An
      increase in the rate of O2 uptake was observed 1 h after cells were irradiated
      with doses of 6-10 Gy. The radiation-induced increase in respiration could be
      blocked by oligomycin, an inhibitor of mitochondrial ATP synthase, suggesting
      control by increased cytoplasmic ATP turnover. The stimulation of respiration was
      not associated with changes in the activity of mitochondrial electron transfer
      enzymes or permeability of the inner membrane. Several inhibitors of processes
      which used ATP were screened for their effects on the basal respiration rate and
      on the radiation response. In irradiated thymocytes, an enhancement of inhibition
      of respiration by ouabain, La3+ and cycloheximide was observed. These results
      indicate that the radiation-induced stimulation of respiration is due to changes
      in ion homeostasis and protein synthesis. The effect of X irradiation was shown
      to be independent of the redox status of nonprotein thiols and was not associated
      with detectable changes in some products of lipid peroxidation. The radiation
      induced decrease in activity of superoxide dismutase suggests free radical
      involvement in deleterious effects of radiation.

PMID- 8146291
TI  - Relationship of five anthropometric measurements at age 18 to radiation dose
      among atomic bomb survivors exposed in utero.
AB  - Five body measurements--standing height, body weight, sitting height, chest
      circumference and intercristal diameter--of 18-year-old atomic bomb survivors
      exposed in utero in Hiroshima and Nagasaki were analyzed in relation to DS86
      uterine dose. Age in utero was divided into four periods: 0-7, 8-15, 16-25 and >
      or = 26 weeks. This categorization is based upon the study of radiation-induced
      brain damage. The linear regression analyses for these five variables showed
      significant decreases with increasing dose. The regression coefficients were 
      2.65 cm/Gy for standing height, -2.46 kg/Gy for body weight, -0.92 cm/Gy for
      sitting height, -1.37 cm/Gy for chest circumference and -0.32 cm/Gy for
      intercristal diameter. The multivariate test statistic for the overall dose
      effect on five body measurements was significant, but the interaction between
      dose and gestational period was not significant. Principal-component analysis was
      applied to the five variables. For the first-component scores, the dose effect
      was significant, but the interaction between dose and gestational period was not
      significant. For the second-component scores, the dose effect was significant
      specifically at 0-7 weeks. The radiation dose effect on the second principal
      component found at 0-7 weeks of gestation suggests that malformations occur in
      this period.

PMID- 8146292
TI  - Immune responses to Epstein-Barr virus in atomic bomb survivors: study of
      precursor frequency of cytotoxic lymphocytes and titer levels of anti-Epstein
      Barr virus-related antibodies.
AB  - Precursor frequencies of cytotoxic lymphocytes to autologous Epstein-Barr virus
      transformed B cells and serum titers of anti-Epstein-Barr virus-related
      antibodies were measured in 68 atomic bomb survivors to clarify the immune
      mechanism controlling Epstein-Barr virus infection. The precursor frequency was
      negatively correlated with the titer of anti-early antigen IgG, which is probably
      produced at the stage of viral reactivation. A positive correlation between the
      precursor frequency and titer of anti-Epstein-Barr virus-associated nuclear
      antigen antibody was also observed, indicating that the precursor frequency
      reflects the degree of in vivo destruction by T cells of the virus-infected
      cells. These results suggest that T-cell memory specific to Epstein-Barr virus
      keeps the virus under control and that the precursor frequency assay is useful
      for the evaluation of immune responses to Epstein-Barr virus. However, no
      significant effect of atomic bomb radiation on the precursor frequency was
      observed in the present study, probably due to the limited number of
      participants.

PMID- 8146293
TI  - Effect of exposure to low-dose gamma radiation during late organogenesis in the
      mouse fetus.
AB  - The abdominal region of pregnant Swiss mice was exposed to 0.05 to 0.50 Gy of
      gamma radiation on day 11.5 postcoitus. The animals were sacrificed on day 18 of
      gestation and the fetuses were examined for mortality, growth retardation,
      changes in head size and brain weight, and incidence of microphthalmia. No marked
      increase in fetal mortality or growth retardation was observed below 0.25 Gy; the
      increase in these parameters was significant only at 0.50 Gy. A significant
      reduction in head size and brain weight and a significant increase in the
      incidence of microphthalmia were observed at doses above 0.15 Gy. Detectable
      levels of microcephaly and microphthalmia were evident even at 0.10 Gy. A linear
      dose response was seen for these effects in the dose range of 0.05 to 0.15 Gy. It
      is concluded that the late period of organogenesis in the mouse, especially
      between days 10 and 12 postcoitus, is a particularly sensitive phase in the
      development of the skull, brain and eye.

PMID- 8146294
TI  - Enhancement of thermal sensitivity of xenografted human DLD-2 tumors by
      administration of basic fibroblast growth factor.
AB  - It has previously been shown that administration of basic fibroblast growth
      factor (FGF-2) to mice bearing xenografted human DLD-2 carcinomas produces
      significant increases in tumor growth rates and decreased intratumor hypoxia,
      effects which appear to be secondary to changes in the vasculature. In this
      study, we treated DLD-2 tumors with FGF-2 (ip, 0.25 mg/kg, q.i.d. x 7) beginning
      on day 15 after implantation, when average tumor volumes were 238 mm3. One day
      after cessation of administration of FGF-2 (day 22 after implantation, average
      tumor volume 1748.1 mm3), clamped tumors were given hyperthermia (42.5 degrees C,
      60 min) by water bath heating. The slower-growing tumors in the control mice
      (sham-injected with Hanks' basic salt solution) were clamped and subjected to
      hyperthermia treatment at equivalent average tumor volumes (1882.7 mm3), which
      occurred on day 26 after implantation. Tumors in control groups were clamped but
      not heated. The time needed for neoplasms to grow to twice their volumes at the
      time of hyperthermia treatment was 68 days for the FGF-2-treated neoplasms and 47
      days for the controls, while 26 and 31 days were needed for the control groups
      which were not treated with heat. The relative growth delay induced by
      hyperthermia is therefore 16 (47-31) days for control neoplasms and 42 (68-26)
      days for FGF-2-treated tumors. Therefore, tumors in the mice injected with FGF-2
      were significantly more sensitive to the hyperthermia than controls, by a factor
      of about 2.6 (42/16). This result indicates that administration of growth factors
      such as FGF-2 to mice bearing tumors may produce an increased sensitivity of the
      tumors to hyperthermia.

PMID- 8146295
TI  - The inverse dose-rate effect and the extrapolation of radon risk estimates from
      exposures of miners to low-level exposures in homes.

PMID- 8146296
TI  - A study of the excited states in cytosine and guanine stacks in the Hartree-Fock
      and exciton approximations.
AB  - We report calculated exciton energies for the cytosine and guanine stacks
      obtained in the ab initio Hartree-Fock crystal orbital and exciton approximation,
      which includes the excited electron-hole interaction. This interaction plays an
      important role in the description of excited electron spectra in the low-energy
      region. The stacks were chosen as examples of polymers with helical symmetry.

PMID- 8146297
TI  - In vivo induction of O6-alkylguanine-DNA-alkyltransferase in response to indium
      114m.
AB  - The effect of systemic administration of the radionuclide 114mIn on O6
      alkylguanine-DNA-alkyltransferase (ATase) activity has been examined in rats. In
      response to 14.8 MBq/kg 114mIn injected intraperitoneally, hepatic ATase was
      induced maximally approximately fivefold at 7 days after injection, at which time
      the cumulative radiation dose to the liver was approximately 2 Gy. At 63 days
      after injection ATase activity was still approximately twofold elevated and
      remained so at 126 days after injection. By 200 days after injection ATase
      activity had returned to control values. The 114mIn content of the liver
      increased to a maximum of 28.7 kBq/g 48-72 h after injection, after which it
      began to decrease such that at 126 days only 0.3 kBq/g remained and at 200 days
      0.03 kBq/g. In response to 4.44 MBq/kg 114mIn, hepatic ATase was induced twofold
      by 7 days after injection, when the liver had received a radiation dose of 0.6
      Gy, and was still slightly elevated at 63 days. There was no ATase induction
      after 0.44 MBq/kg 114mIn up to 7 days after injection; however, at 42 days after
      injection activity was approximately twofold higher. These results suggest that
      induction of hepatic ATase activity by 114mIn is dependent upon cumulative
      radiation dose and dose rate; both must be above minimum threshold values for
      induction to occur. The induction of a DNA repair enzyme by radiation exposure
      from an internal radionuclide may have important consequences for risk
      assessments of occupational, medical and environmental exposures.

PMID- 8146298
TI  - Evidence that the product of the xrs gene is predominantly involved in the repair
      of a subset of radiation-induced interphase chromosome breaks rejoining with fast
      kinetics.
AB  - We classified interphase chromosome breaks into alpha and beta forms to study the
      requirement for the xrs gene product in the repair of each of these forms of
      damage. The alpha form of damage comprises radiation-induced interphase
      chromosome breaks whose rejoining is slow and sensitive to treatment with beta
      arabinofuranosyladenine (beta-araA), whereas the beta form of damage comprises
      interphase chromosome breaks whose rejoining is fast and sensitive to treatment
      in hypertonic medium. Interphase chromosome breaks of the alpha form are
      visualized in plateau-phase cells by premature chromosome condensation (PCC)
      carried out in the absence of any treatment during the condensation period. More
      interphase chromosome breaks of the alpha form can be uncovered by treatment with
      beta-araA during the period of PCC. Interphase chromosome breaks of the beta form
      are not visualized in experiments using standard PCC protocols but can be
      uncovered by treatment in hypertonic growth medium during the period allowed for
      PCC. In the present report, we show that the yield of interphase chromosome
      breaks of the alpha form is similar in CHO and xrs-5 cells and demonstrate that
      xrs-5 cells rejoin this type of interphase chromosome breaks with an efficiency
      similar to that observed in repair-proficient CHO cells. Furthermore, we provide
      evidence supporting the notion that xrs-5 cells are deficient in the rejoining of
      the beta form of interphase chromosome breaks. These results strongly suggest
      that the product of the xrs gene is required predominantly in the repair of the
      beta form of interphase chromosome damage and emphasize the need for
      discrimination between different forms of interphase chromosome breaks in
      irradiated cells.

PMID- 8146299
TI  - Inhibition of topoisomerase II alpha activity in CHO K1 cells by 2
      [(aminopropyl)amino]ethanethiol (WR-1065).
AB  - The aminothiol 2-[(aminopropyl)amino]ethanethiol (WR-1065) is the active thiol of
      the clinically studied radioprotective agent S-2-(3
      aminopropylamino)ethylphosphorothioic acid (WR-2721). WR-1065 is an effective
      radiation protector when it is administered 30 min prior to exposure of Chinese
      hamster ovary K1 cells to radiation (i.e., a dose modification factor of 1.4) at
      a concentration of 4 mM. Under these exposure conditions, topoisomerase (Topo) I
      and II alpha activities and associated protein contents were measured in cells of
      the K1 cell line using the DNA relaxation assay, the P4 unknotting assay and
      immunoblotting, respectively. WR-1065 was ineffective in modifying Topo I
      activity, but it did reduce Topo II alpha activity by an average of 50%. The
      magnitude of Topo II alpha protein content, however, was not affected by these
      exposure conditions. The effects on the cell cycle were monitored by the method
      of flow cytometry. Exposure of cells to 4 mM WR-1065 for up to 6 h resulted in a
      build-up of cells in the G2/M-phase compartment. However, under these conditions
      and in contrast to Topo II inhibitors used in chemotherapy, WR-1065 is an
      effective radioprotective agent capable of protecting against both radiation
      induced cell lethality and mutagenesis. One of several mechanisms of action
      attributed to aminothiol compounds such as WR-1065 has been their ability to
      affect endogenous enzymatic reactions involved in DNA synthesis and repair and
      progression of cells through the phases of the cell cycle. These results are
      consistent with such a proposed mechanism and demonstrate in particular a
      modifying effect by WR-1065 on Topo II, which is involved in DNA synthesis.

PMID- 8146300
TI  - The effects of incorporation of bromodeoxyuridine into mammalian DNA on the
      migration patterns of DNA fragments subjected to pulsed-field gel electrophoresis
      after X irradiation or cutting with a restriction enzyme.
AB  - Incorporation of bromodeoxyuridine (BrdU) into DNA in both Chinese hamster ovary
      (CHO) cells and human melanoma (U1) cells reduced the rate of DNA migration in
      transverse alternating-field electrophoresis (TAFE) agarose gel optimized for
      separating molecules larger than 2 Mb. This "BrdU migration effect" was
      independent of the method of damaging the DNA; i.e., the effect was observed
      after irradiation of the cells or treatment of the plugs containing DNA with the
      restriction enzyme, Mlu-1, and similar results were found for CHO and U1 cells.
      However, when the amount of cutting of DNA was estimated from the amount of DNA
      migrating from the plugs, a difference between U1 cells and CHO cells was
      observed in that incorporation of BrdU enhanced the cutting of DNA by either
      irradiation or Mlu-1 digestion for U1 cells but not for CHO cells. Therefore, the
      "BrdU migration effect" could not be attributed to an increase in large molecules
      because of reduced cutting of the BrdU-labeled DNA. The decrease in migration
      rate during pulsed-field gel electrophoresis when BrdU replaces thymidine in the
      DNA is hypothesized to result from the increase in negative charge on BrdU
      labeled DNA. An increase in electron charge density is expected to increase the
      reorientation time of BrdU-labeled DNA fragments during each voltage pulse due to
      an increase in the elongation length of the DNA caused by an increase in
      electronegativity.

PMID- 8146301
TI  - A benchmark of cell survival models using survival curves for human cells after
      completion of repair of potentially lethal damage.
AB  - Six models of radiation action (the linear-quadratic model, the multitarget model
      with initial slope, the repair-misrepair model, the lethal-potentially lethal
      model, the cybernetic model, the saturable repair model) were tested for their
      goodness of fit to survival curves for human cells. Fifty-three survival curves
      for human cells irradiated in plateau phase and after completion of repair of
      potentially lethal damage (PLD) provided the experimental basis for the tests.
      Three criteria were considered. The capacity to describe the survival data was
      estimated, using the error left unexplained by the model. A validation of models
      was achieved by consideration of the mean residual squared errors. The ability of
      the parameters to characterize survival curves was investigated, studying their
      variation within and among curves. The models were not equivalent, whatever the
      test. The saturable repair model and the multitarget with initial slope model
      gave the most accurate description of survival data. The linear-quadratic model
      had the most reliable parameters, so that comparisons of the cell survival curves
      could be made advantageously. The cybernetic model and the lethal-potentially
      lethal model were found inappropriate for the analysis of survival curves for
      human cells after completion of PLD repair.

PMID- 8146302
TI  - Kinetics of micronuclei induced by 125IdU in cells of two lines.
AB  - The kinetics of the formation of cells carrying micronuclei (MN) after one
      doubling time (td) incorporation of 125I-iododeoxyuridine (125IdU) to Chinese
      hamster ovary (CHO) and rat anterior pituitary tumor (GC) cells was studied.
      Uptake of 125IdU by cells of both cell lines was linearly dependent on the
      concentration of extracellular 125I activity. The postlabeling time-dependent
      decrease in cellular activity of 125IdU was exponential in CHO cells and
      approximately linear in GC cells. The maximum yield of MN was seen during the
      second and third td after 125IdU incorporation. The frequency of cells with
      micronuclei increased monotonically with dose in the interval (1, 40) 125I decays
      cell-1td-1. The dose-response relationship could be fitted by straight lines with
      slopes of 1.0 (CHO) and 1.2 (GC) on the subinterval (1, 10) and of 0.6 or 0.5,
      respectively, for the subinterval (10, 40). Below one 125I decay cell-1td-1, the
      mean frequency of micronucleated binuclear cells was significantly lower than
      (CHO) or equal to (GC) the control. On average, one 125I decay/cell induced 0.95
      +/- 0.5% (CHO) or 1.0 +/- 0.5% (GC) of micronucleated binuclear cells.

PMID- 8146303
TI  - Neoplastic transformation dose response of oncogene-transfected rat embryo cells
      by gamma rays or 6 MeV alpha particles.
AB  - We measured a dose-response relationship for induction of neoplastic
      transformation by 6 MeV alpha particles and 137Cs gamma rays in REC:myc and
      REC:ras cells, that is, rat embryo cells (REC) transfected with the c-myc or the
      Ha-ras oncogenes. The 6 MeV alpha particles simulated 222Rn emissions for risk
      assessment relative to low-LET radiations. The dose of gamma rays was
      approximately twice that of alpha particles for a neoplastic transformation
      frequency of 10(-3). The survival of the REC cells containing oncogenes was
      comparable to that of the commonly used C3H 10T1/2 cells for the same dose, but
      the former were more refractory to radiation-induced neoplastic transformation.
      Neoplastic transformation frequency measured in REC cells was 3 times lower than
      those typically measured in C3H 10T1/2 cells at a gamma-ray dose of 6 Gy, and 5
      10 times lower at an alpha-particle dose of 3 Gy.

PMID- 8146304
TI  - In vitro radiation-induced neoplastic progression of low-grade uroepithelial
      tumors.
AB  - Recent interest has focused on the identification of molecular genetic mechanisms
      in multistep neoplastic transformation. In vitro exposure of simian virus 40
      (SV40)-immortalized human uroepithelial cells (SV-HUC) that are environmentally
      relevant to bladder carcinogens has been shown to produce tumorigenic
      transformation, as assessed by the ability of cells exposed to a carcinogen to
      form xenograph tumors with heterogeneous cancer phenotypes ranging from very
      aggressive, invasive high-grade carcinomas to superficial low-grade indolent
      tumors. In addition, exposure of a low-grade indolent tumor generated in the SV
      HUC system, MC-T11, to the same carcinogens results in neoplastic progression as
      assessed by the production of high-grade aggressive cancers. In the present
      study, we show neoplastic progression of MC-T11 after in vitro exposure to a
      single dose of 6 Gy X rays. In addition, we show that the chromosome deletions,
      including losses of 4q, 11p, 13q and 18, observed in these radiation-induced
      tumors are similar to those observed in carcinogen-induced tumors, thus
      supporting the hypothesis that the experimental cell system, not the transforming
      agent, dictates the genetic losses required for tumorigenic transformation and
      progression.

PMID- 8146305
TI  - Protonation of nucleobase anions in gamma-irradiated DNA and model systems. Which
      DNA base is the ultimate sink for the electron?
AB  - Electron spin resonance (ESR) spectroscopy has been used to investigate
      irreversible protonations of the nucleobase anions in gamma-irradiated frozen
      aqueous solutions of dGMP-dCMP, polyG-polyC, poly[dGdC].poly[dGdC], dAMP-dTMP,
      poly[dAdT].poly-[dAdT] and DNA itself. Analysis of the ESR spectra at a dose of
      22 kGy shows that fractional conversion of total radicals to carbon-protonated
      species on annealing is in the order: dAMP-dTMP (43%) > pdAdT = DNA (23%) >
      dGMP.dCMP (15%) > poly-dGdC.polydGdC (6%) > polyG.polyC (3%). Two hydrogen
      addition radicals make contributions to the polyG.polyC, poly-[dGdC].poly[dGdC]
      and dGMP.dCMP spectra in H2O on annealing. They are those formed by protonations
      at C6 of the cytosine anion radical, C(C6)H., and at C8 of the guanine anion
      radical, G(C8)H.. Computer analysis reveals that anion protonation reaction in
      dGMP.dCMP results in mainly C(C6)H., whereas protonation reaction in polyG.polyC
      and poly[dGdC].poly-[dGdC] yields mainly G(C8)H.. In dAMP.dTMP and
      poly[dAdT].poly[dAdT] as in DNA itself, the only DNA base found to undergo an
      irreversible protonation at a carbon site is thymine, resulting in T(C6)H.. The
      conversion of DNA anion to T(C6)H. is found to be dependent on dose. At low doses
      (5 kGy), about 30% conversion to T(C6)H. is found, whereas at high doses (94
      kGy), only 13% conversion is found. The dose dependence is ascribed in part to
      ion radical recombinations whose probabilities are increased at high doses. A
      consideration of the rates of protonations of the purine and pyrimidine anion
      radicals as well as the differences in electron affinities suggest carbon
      protonation reactions of DNA base anions in irradiated stacked double-strand DNA
      at 37 degrees C would be predominantly at thymine and perhaps guanine, whereas in
      single-strand DNA all bases would contribute.

PMID- 8146306
TI  - Induction of stable p53 oncoprotein and of c-myc overexpression in cultured
      normal human uroepithelium by radiation and N-nitrosodiethanolamine.
AB  - Uroepithelium cultured from normal patients without cancer (60 individuals) was
      found to segregate into four subtypes based on the level of carcinogen treatment
      needed to induce abnormal p53 and c-myc. Twenty-two percent of patient cultures
      never showed abnormal p53 expression, even after chronic exposure to
      nitrosamines, in addition to irradiation. In these cultures, c-myc expression was
      confined to viable, normal-appearing cells at the growing edge of the culture and
      to apoptotic bodies. Twenty-eight percent of cultures were negative for abnormal
      p53 unless challenged with both radiation and chronic administration of
      nitrosamines, while a further 26% required only a single dose of radiation to
      induce the abnormal protein. The remaining patients had tissue which, while
      initially negative for stable p53, became positive when put into culture and
      stimulated to grow. The c-myc protein was overexpressed in all cultures with
      abnormal p53. It would appear that elevated expression of conformationally
      inactive p53 and of high levels of c-myc represents an early response of normal
      uroepithelial cells to carcinogen challenge. It also appears that a relatively
      high number of patients without cancer express these proteins when their cells
      are challenged to grow; a pre-exposure to environmental carcinogens such as
      nitrosamines in cigarette smoke is likely to be involved.

PMID- 8146307
TI  - Radiation brain injury is reduced by the polyamine inhibitor alpha
      difluoromethylornithine.
AB  - Alpha-difluoromethylornithine (DFMO) was used to reduce 125I-induced brain injury
      in normal beagle dogs. Different DFMO doses and administration schedules were
      used to determine if the reduction in brain injury was dependent on dose and/or
      dependent upon when the drug was administered relative to the radiation
      treatment. Doses of DFMO of 75 mg/kg/day and 37.5 mg/kg/day given 2 days before,
      during and for 14 days after irradiation reduced levels of putrescine (PU) in the
      cerebrospinal fluid relative to controls. Volume of edema was significantly
      reduced by 75 mg/kg/day of DFMO before, during and after irradiation and by the
      same dose when the drug was started immediately after irradiation. A reduction in
      edema volume after 37.5 mg/kg/day before, during and after irradiation was very
      near significance. Ultrafast CT studies performed on dogs that received a DFMO
      dose of 75 mg/kg/day before, during and after irradiation suggested that the
      reduced edema volume was associated with reduced vascular permeability. Volume of
      necrosis and volume of contrast enhancement (breakdown of the blood-brain
      barrier) were significantly lower than controls only after a DFMO dose of 75
      mg/kg/day before, during and after irradiation. These latter data, coupled with
      the findings relative to edema, suggest that different mechanisms may be involved
      with respect to the effects of DFMO on brain injury, or that the extents of
      edema, necrosis and breakdown of the blood-brain barrier may depend upon
      different levels of polyamine depletion. The precise mechanisms by which DFMO
      exerts the effects observed here need to be determined.

PMID- 8146308
TI  - Molecular, cellular, and genetic basis of radiosensitivity at low doses: a case
      of inducible repair?
AB  - Many proteins are induced by ionizing radiation, and genes are activated. We
      still do not know which, if any, are responsible for IRR, or what leads to the
      adaptive response seen at still lower doses. Are these the same responses? Are
      they related to apoptosis, repair of potentially lethal damage and other
      responses? Does the cell have a whole battery of responses, depending on the
      dose? I suspect this is the case. Can the responses be explained more simply, as
      effects on regulators of cell cycle or induction of fidelity, or is there
      induction of repair? Are there still other explanations for the apparent
      protection? The initial slope of the survival curve which was addressed earlier
      (1) must take on new meaning given the hyperradiosensitive portion. Similarly, we
      may have to change our thinking with respect to the LQ description of survival
      data. It is not surprising that this workshop, held at such an early stage
      primarily to address the phenomenon of increased radioresistance, produced more
      questions than answers. Single-strand breaks may trigger resistance, but
      additional lesions or classes of damage may be relevant. Some physicists expect
      the damage caused to be linear with dose; the biologists suggest that the
      response is nonlinear (e.g. saturation of an enzyme, induction of repair, cell
      cycle effects) and there is room for biochemistry which could also vary with dose
      (e.g. consumption of a protector or a sensitizer). Some biophysicists would argue
      that the observed structures in survival curves might be explained by change in
      the target cross section such as a large change in DNA conformation caused by a
      very low dose. There is some reluctance in the radiobiology community to accept
      that cells may respond to ionizing radiation by inducing or activating protective
      mechanisms, although the cell exhibits defensive responses to many other
      detrimental stimuli. If "the heart of the matter is in the shape of the survival
      curve" as suggested by Dr. Elkind in his summary of the 1974 "low doses"
      conference (p. 385 in ref. 1), then we are fortunate indeed that there are now
      additional methods to attack the question directly of what is turned on or
      activated. It is anticipated that there will be many further developments within
      the year, to be presented at related sessions at larger meetings, and at a
      closely related meeting to be held in June 1994 in Montreal, entitled "Gene
      Induction and Adaptive Responses in Irradiated Cells: Mechanisms and Clinical
      Implications."

PMID- 8146309
TI  - Estimation of the initial slope of the cell survival curve after irradiation from
      micronucleus frequency in cytokinesis-blocked cells.
AB  - We have already reported that the alpha/beta ratio of the cell survival curve
      could be estimated from the micronucleus frequency in cytokinesis-blocked cells
      treated with cytochalasin-B after irradiation. In this paper, we investigate the
      direct relationship between the alpha value and the appearance of micronuclei.
      Cells of the SCCVII, RIF-1, EMT6, V-79, CHO, HeLa and human esophageal cancer
      cell lines were used for the study. Low-dose-rate irradiation was used to
      determine the alpha component of the relationship between dose and micronucleus
      frequency according to the linear-quadratic (LQ) model. A reduction of the dose
      rate from 3.09 to 0.0142 Gy/min correspondingly decreased the micronucleus
      frequency; however, the fraction of binucleate cells without micronuclei was not
      affected in SCCVII and RIF-1 cells. When this fraction was defined as the normal
      nuclear division fraction, it decreased exponentially as a function of radiation
      dose. Then dose vs normal nuclear division fraction (NNDF) was fitted as follows:
      -ln NNDF = aD + C, where D is radiation dose in grays and C is constant. The
      slope of the dose vs normal nuclear division fraction was not affected by dose
      rate. The correlation was also explored between the slope (a) and the alpha value
      of the cell survival curve determined by the colony formation assay in cells of
      eight cell lines. These two values showed extremely high agreement: alpha = 1.01
      a + 0.00795 (r = 0.99, P < 0.01). This assay was applied to estimate the alpha
      value of the cell survival curve of human esophageal cancer cell lines
      established from surgical specimens.

PMID- 8146310
TI  - Genome lability in radiation-induced transformants of C3H 10T1/2 mouse
      fibroblasts.
AB  - We have been investigating radiation-induced neoplastic transformants of C3H
      10T1/2 mouse fibroblasts for evidence of heritable changes. C3H 10T1/2 cells were
      treated with 8 Gy X rays. After approximately 8 weeks of culture, type II/III
      foci were isolated from the monolayer using cloning rings. Cell lines developed
      from these foci, and clones established from these cell lines, were examined for
      DNA content. The isolated focus-derived populations and derived clones often
      display aneuploidy and/or polyploidization. In one instance a clone (derived from
      a single cell) displayed multiple polyploidies. During passage the ploidy of many
      of the anomalous populations gradually reverted to the ploidy of the non
      neoplastically transformed state. The morphological features associated with the
      neoplastic transformation event were nevertheless retained. The results
      demonstrate that exposure to radiation can induce, in association with
      morphological neoplastic transformation, a heritable, genomically labile state.

PMID- 8146311
TI  - Influence of cell cycle phase on radiation-induced cytotoxicity and DNA damage in
      human colon cancer (HT29) and Chinese hamster ovary cells.
AB  - We have previously shown that fluorodeoxyuridine (FdUrd) radiosensitizes HT29
      human colon carcinoma cells. Since treatment with FdUrd arrests cells at the G1/S
      phase interface, a condition associated with increased radiation sensitivity in
      some cells, it seemed possible that redistribution of cells in the phases of the
      cell cycle might account for FdUrd-mediated radiosensitization. To begin to test
      this, HT29 cells were separated by centrifugal elutriation according to cell
      cycle phase and assessed for radiosensitivity, using a clonogenic assay, and
      radiation-induced DNA damage, using pulsed-field gel electrophoresis. We found
      that all of the elutriated fractions (which contained cells enriched in G1,
      G1/early S, mid to late S or G2/M phase) had the same radiation sensitivity and
      expressed a similar extent of radiation-induced DNA damage. To determine if the
      techniques used in this study could detect differences between the radiation
      sensitivity of cells in different phases of the cell cycle, analogous experiments
      were carried out using Chinese hamster ovary (CHO) cells. In contrast with the
      results of experiments with HT29 cells, but in agreement with previous studies,
      CHO cells separated under the same conditions as were used for HT29 cells showed
      a marked dependence on cell age of both clonogenic survival and radiation-induced
      DNA damage. Thus, within the limitations of the purity of separation obtained
      using elutriation, the radiation sensitivity of HT29 cells does not vary
      substantially as a function of cell cycle phase. Therefore, it seems unlikely
      that cell cycle redistribution alone explains the radiation sensitivity produced
      by exposure to FdUrd.

PMID- 8146312
TI  - The effect of radiosensitizers on the survival response of hypoxic mammalian
      cells: the low X-ray dose region, hypersensitivity and induced radioresistance.
AB  - It has been shown previously that the extent of chemical modification of the
      hypoxic radiation response is dependent on dose. Some types of sensitizer are
      more effective at low doses (to 4 Gy) than at higher doses. Since such drugs are
      possible adjuvants to radiotherapy, the mechanisms responsible for the variable
      response at clinical doses are of interest. Existing reports on sensitization at
      low doses are summarized, and the effects of cisplatin and buthionine sulfoximine
      on the purported induced response to radiation in hypoxic cells are presented.
      Cisplatin at a low, nontoxic concentration (1 microM) appears to abolish the
      increased radioresistant portion of the survival response. A role for high
      mobility-group protein binding by platinum drugs is hypothesized to explain their
      interaction with radiation, and conversely, it is suggested that the heretofore
      unexplained different behavior of certain hypoxic sensitizers at low doses could
      be, at least in part, an effect on the induction of resistance.

PMID- 8146313
TI  - The effect of two topoisomerase inhibitors on low-dose hypersensitivity and
      increased radioresistance in Chinese hamster V79 cells.
AB  - A preliminary investigation of the effect of topoisomerase inhibitors on the
      structure of the survival curve at low doses has been carried out in Chinese
      hamster V79 cells, where there is a deviation from the predicted response to
      radiation (Marples and Joiner, Radiat. Res. 113, 41-51, 1993). Cells were treated
      with one representative drug for each enzyme (topoisomerase I or II) prior to X
      irradiation in air and assessed for cell survival using automated microscopic
      location of cells. VP-16 causes little or no effect, while camptothecin has a
      measurable effect up to 2 Gy. The results are discussed in terms of the role of
      DNA damage and cell cycle in increased radioresistance, which encourage further
      investigation of the effects of this class of drugs at low doses.

PMID- 8146314
TI  - Enhanced malignant transformation is accompanied by increased survival recovery
      after ionizing radiation in Chinese hamster embryo fibroblasts.
AB  - Transformed Chinese hamster embryo fibroblasts (CHEF), which gradually increase
      in tumor-forming ability in nude mice, were isolated from normal diploid CHEF/18
      cells. Transformed CHEF cells (i.e. T30-4 > 21-2M3 > 21-2 > normal CHEF/18)
      showed gradual increases in potentially lethal damage (PLD) survival recovery.
      beta-Lapachone and camptothecin, modulators of topoisomerase I (Topo I) activity,
      not only prevented survival recovery in normal as well as in tumor cells, but
      enhanced unscheduled DNA synthesis. These seemingly conflicting results are due
      to the fact that Topo I activity can be modulated by inhibitors to convert single
      stranded DNA lesions into double-stranded breaks. Increases in unscheduled DNA
      synthesis may result from a continual supply of free ends, on which DNA repair
      processes may act. Altering Topo I activity with modulators appears to increase X
      ray lethality via a DNA lesion modification suicide pathway. Cells down-regulate
      Topo I immediately after ionizing radiation to prevent Topo I-mediated lesion
      modification and to enhance survival recovery.

PMID- 8146315
TI  - A preliminary investigation into the extent of increased radioresistance or hyper
      radiosensitivity in cells of hamster cell lines known to be deficient in DNA
      repair.
AB  - The response to low doses of X rays was assessed in cells of three hamster cell
      lines which are defective in DNA repair and was compared with their parental
      lines. Cells of the V79-derived double-strand break repair-deficient line XR-V15B
      showed no radioresistance in the 0.5-Gy range compared with the V79B wild type,
      but instead showed an exponential response. Cells of the single-strand break
      repair-deficient line EM9 showed hyper-radiosensitivity and exhibited increased
      radioresistance. Most interestingly, cells of the UV-20 cell line appeared to
      respond exponentially, as a continuation of the hyper-radiosensitive portion of
      the curve, with no evidence of increased radioresistance. This line is defective
      in an incision step of excision repair and is sensitive to crosslinking agents.
      Further studies are warranted to address the possible role of single- and double
      strand break repair and excision repair in hyper-radiosensitivity and increased
      radioresistance.

PMID- 8146316
TI  - Ionizing radiation and cell cycle progression in ataxia telangiectasia.
AB  - Exposure of mammalian cells to ionizing radiation causes delay in normal progress
      through the cell cycle at a number of different checkpoints. Abnormalities in
      these checkpoints have been described for ataxia telangiectasia cells after
      irradiation. In this report we show that these abnormalities occur at different
      phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells.
      Ataxia telangiectasia cells, synchronized in late G1 phase with either mimosine
      or aphidicolin and exposed to radiation, showed a reduced delay in entering S
      phase compared to irradiated control cells. Failure to exhibit G1-phase delay in
      ataxia telangiectasia cells is accompanied by a reduced ability of radiation to
      activate the product of the tumor suppressor gene p53, a protein involved in G1/S
      phase delay. When the progress of irradiated G1-phase cells was followed into the
      subsequent G2 and G1 phases ataxia telangiectasia cells showed a more pronounced
      accumulation in G2 phase than control cells. When cells were irradiated in S
      phase the extent of delay was more evident in G2 phase and ataxia telangiectasia
      cells were delayed to a greater extent. These results suggest that the lack of
      initial delay in both G1 and S phases contributes to the radiosensitivity
      observed in this syndrome.

PMID- 8146317
TI  - The effect of oxygen on low-dose hypersensitivity and increased radioresistance
      in Chinese hamster V79-379A cells.
AB  - Chinese hamster V79 cells irradiated in air are hypersensitive to X-ray doses
      less than 0.5 Gy and show an increased radioresistance over the dose range 0.5-1
      Gy (Marples and Joiner, Radiat. Res. 133, 41-51, 1993). Of considerable interest
      from both a mechanistic and clinical viewpoint is the response of hypoxic cells
      over this dose range. The data presented here indicate that hypoxic cells are
      also hypersensitive to low X-ray doses and exhibit an increased radioresistant
      response, albeit triggered at a somewhat higher dose (0.69 Gy, SEM +/- 0.18 Gy)
      than observed in oxygenated cells (0.5 Gy, SEM +/- 0.21 Gy). These data indicate
      that the triggering event for increased radioresistance may be independent of
      oxygen. As reported by others previously, the oxygen enhancement ratio was found
      to decrease with a decreasing X-ray dose.

PMID- 8146318
TI  - Can colony size be used to detect low-dose effects?
AB  - Many insults at low doses are defined as nontoxic, even though obvious effects do
      occur. Among these are changes in colony size when clonogenic survival is
      assessed. Early attempts to quantify radiation effects on colony size have been
      reported, but the time-consuming nature of these experiments did not encourage
      the use of this parameter as an end point. Recently, however, developments in
      image cytometry technology have provided alternative, less labor-intensive means
      of measuring colony size. These techniques have been used in our ongoing
      investigations of radiation effects at low doses. Data accumulated to date show a
      measurable dose dependence of colony size in clones classed as survivors. This
      dose dependence is characterized by fluctuations in the 0-1.5-Gy dose range,
      followed by a gradual decrease in colony size at higher doses. The fluctuations
      at low doses correspond qualitatively to the concavity, thought to be indicative
      of inducible repair phenomena, that has been observed in cell survival curves in
      the same dose range. This concavity was also seen in the current study, but its
      detection appeared to be dependent on the method used to score survivors.

PMID- 8146319
TI  - Radiosensitivity of human cell lines to small doses. Are there some clinical
      implications?
AB  - The concept of intrinsic radiosensitivity is now strongly associated with the
      linear-quadratic (LQ) model which is currently the best and the most reliable
      method to fit the first three decades of a survival curve for both human
      fibroblast and human tumor cell lines. This approach has led to the major
      conclusions that it is the initial part, and not the distal part, of the survival
      curve which truly characterizes intrinsic cellular radiosensitivity and there is
      a correlation between the parameters describing mainly the initial part of the
      survival curve (alpha, SF2, D) and the clinical radioresponsiveness. More
      accurate analysis with flow cytometry or a dynamic microscopic image processing
      scanner (DMIPS) has allowed further study of the survival curve which has shown
      two sorts of substructure. On one hand, the overall survival curve of
      exponentially growing cells is described by two or more sets of alpha, beta
      parameters (heterogeneity in radiosensitivity due to the cell cycle). On the
      other hand, hypersensitivity at very low doses (< 0.5 Gy) followed by an increase
      of the radioresistance of the whole population at higher doses has also been
      observed. This phenomenon is not described by the conventional LQ model and has
      been interpreted as an induced radioresistance which seems to be negatively
      correlated with intrinsic radiosensitivity. In clinical radiotherapy, there are
      two sorts of response of normal tissues: (1) the early and late damage and (2)
      the carcinogenesis. Concerning the first point, the clinically detectable
      radiation damage appears at doses usually around 20 Gy (in 2-Gy fractions) with
      the exception of the hemopoietic and the lymphatic tissues. Therefore, the small
      doses delivered at the edges or in the penumbrae of treatment fields in routine
      radiotherapy cannot create detectable damage, despite a potentially much higher
      effect per unit dose, because the total doses are still very small. However, it
      may be important to bear in mind the possible extra effect of low doses outside
      the target volume if regions in the vicinity are subsequently retreated.
      Concerning clinical radiation-induced carcinogenesis, three studies described a
      higher relative risk associated with small doses per fraction or very low dose
      rate. The results and the interpretation of these studies are discussed.

PMID- 8146320
TI  - Radiation-induced adaptive response for protection against micronucleus formation
      and neoplastic transformation in C3H 10T1/2 mouse embryo cells.
AB  - We have monitored the end points of cellular survival, micronucleus formation and
      neoplastic transformation frequency to assess adaptation to ionizing radiation in
      the C3H 10T1/2 mouse embryo cell system. Plateau-phase cells were pre-exposed to
      an adapting dose of 0.1 to 1.5 Gy low-dose-rate gamma radiation 3.5 h prior to an
      acute challenge dose of 4 Gy. No adapting dose improved clonogenic survival
      detectably, whether the cells were plated immediately after the acute exposure or
      held in plateau phase for 3.5 h before plating. However, all chronic adapting
      doses resulted in both a reduction in micronucleus frequency in binucleate cells
      and about a twofold reduction in neoplastic transformation frequency per viable
      cell when cells were subsequently exposed to the 4-Gy challenge dose. Our data
      suggest that a low-dose-rate pre-exposure to ionizing radiation induces an
      adaptive response in C3H 10T1/2 cells, and that this response enhances DNA double
      strand break repair when cells are subsequently exposed to a second radiation
      dose. This enhanced repair appears to be error-free since these adapted cells are
      also less susceptible to radiation-induced neoplastic transformation.

PMID- 8146321
TI  - Multiphasic survival curves for cells of human tumor cell lines: induced repair
      or hypersensitive subpopulation?
AB  - Survival of the cells of three human tumor cell lines of differing
      radiosensitivity was measured after irradiation with single doses of X rays (0.05
      5 Gy). At doses below 1 Gy, cells were more radiosensitive than predicted by back
      extrapolating the high-dose response. This difference was more marked for cells
      of the radioresistant cell lines than the radiosensitive cell line so that the
      "true" initial slopes of the survival curves, at very low doses, were similar for
      the cells of the three cell lines. This phenomenon could reflect an induced
      radioresistance so that low doses of X rays are more effective per gray than
      higher doses, because only at higher doses is there sufficient damage to trigger
      repair systems or other radioprotective mechanisms which can then act during the
      time course for repair of DNA injury.

PMID- 8146322
TI  - The role of constitutive and inducible processes in the response of human
      squamous cell carcinoma cell lines to ionizing radiation.
AB  - The inherent radiation sensitivity of the cells within a tumor is thought to
      contribute to the success or failure of radiation therapy. In vitro studies have
      shown that differences in the radiation sensitivity of squamous cell carcinoma
      cell lines reflect alterations in DNA repair. These alterations result from
      constitutive changes in chromosome organization, not radiation-inducible
      processes. While inducible responses may play some role in the radiation response
      of tumor cells, there is no evidence for their involvement in inherent
      differences in tumor cell radiosensitivity or in the success or failure of
      radiotherapy of squamous cell carcinomas.

PMID- 8146323
TI  - Intrinsic radiosensitivity and chromosome aberration analysis using fluorescence
      in situ hybridization in cells of two human tumor cell lines.
AB  - The survival curves for cells of two human tumor cell lines, HT29 and MeWo, have
      been defined using a Dynamic Microscopic Imaging Processing Scanner (DMIPS).
      There are two major differences between these two cell lines: (a) HT29 is more
      radioresistant than MeWo (surviving fraction at 2 Gy of 74 and 27%, respectively)
      and (b) HT29 presents a marked multiphasic survival curve with hypersensitivity
      at low doses (< 0.5 Gy) followed by an increase in radioresistance at higher
      doses which we have interpreted as "induced radioresistance"; this phenomenon is
      much less pronounced for the more radiosensitive cell line MeWo. We have now
      measured in these two cell lines the stable chromosomal aberrations and
      fragments, with the method of fluorescence in situ hybridization (FISH). We have
      analyzed chromosome 4, which does not have spontaneous translocations in either
      of these two cell lines. A dose-effect relationship was studied for radiation
      doses up to 5 Gy. At all doses, both translocations and breaks are more frequent
      in the radiosensitive cell line MeWo compared to the radioresistant cell line
      HT29. The correlation between survival and translocations is different for HT29
      and MeWo, thus indicating that another factor(s) may be involved in cell killing
      in these lines.

PMID- 8146324
TI  - Immediate X-ray-inducible responses from mammalian cells.
AB  - It has been nearly 6 years since we reported the induction of new proteins in
      human normal and tumor cells after ionizing radiation. Since that time there has
      been an explosion of new data and ideas from a number of laboratories regarding
      the immediate responses of human cells to ionizing radiation. The data are,
      however, extremely difficult to interpret since researchers are using confluence
      arrested, log-phase, normal or tumor cells, and are exposing these to a variety
      of doses of ionizing radiation. It is especially difficult to interpret data from
      cells that are exposed to supralethal doses of ionizing radiation. Thus this
      session of the workshop entitled "Molecular, Genetic, and Cellular Basis of
      Radioresistance at Low Doses: A Case Of Inducible Repair?" concentrated on
      inducible responses (both late and immediate) of human cells exposed to
      physiological doses of ionizing radiation. A major focus of future research in
      this field must be directed toward the function(s) of these inducible proteins
      and the expression of genes in DNA repair, cell cycle progression (especially
      radiation-induced cell progression delays) and/or cell death, including
      apoptosis.

PMID- 8146325
TI  - Alterations in transcription factor binding in radioresistant human melanoma
      cells after ionizing radiation.
AB  - We analyzed alterations in transcription factor binding to specific, known
      promoter DNA consensus sequences between irradiated and unirradiated
      radioresistant human melanoma (U1-Mel) cells. The goal of this study was to begin
      to investigate which transcription factors and DNA-binding sites are responsible
      for the induction of specific transcripts and proteins after ionizing radiation
      (Boothman et al., Proc. Natl. Acad. Sci. USA 90, 7200, 1993). Transcription
      factor binding was observed using DNA band-shift assays and oligonucleotide
      competition analyses. Confluence-arrested U1-Mel cells were irradiated (4.5 Gy)
      and harvested at 4 h. Double-stranded oligonucleotides containing known DNA
      binding consensus sites for specific transcription factors were used. Increased
      DNA-binding activity after ionizing radiation was noted with oligonucleotides
      containing the CREB, NF-kappa B and Sp1 consensus sites. Increased DNA binding
      activity after ionizing radiation was noted with oligonucleotides containing the
      CREB, NF-kappa B and Sp1 consensus sites. No changes in protein binding to AP-1,
      AP-2, AP-3 or CTF/NF1, GRE or Oct-1 consensus sequences were noted. X-ray
      activation of select transcription factors, which bind certain consensus sites in
      promoters, may cause specific induction or repression of gene transcription.

PMID- 8146326
TI  - Evidence for induced radioresistance from survival and other end points: an
      introduction.
AB  - A substantial body of data published during the past 30 years makes a strong case
      for the existence of cellular radioprotective mechanisms that can be up-regulated
      in response to exposure to small doses of ionizing radiation. Either these
      "induced" mechanisms can protect against a subsequent exposure to radiation that
      may be substantially larger than the initial "priming" or "conditioning" dose, or
      they may influence the shape of the survival response to single doses so that
      small radiation exposures are more effective per unit dose than larger exposures
      above a threshold where the induced radioprotection is triggered. Evidence for
      these effects comes from studies in vitro with protozoa, algae, higher plant
      cells, insect cells, mammalian and human cells, and studies on animal models in
      vivo. Work at the molecular level is now confirming that changes in levels of
      some cytoplasmic and nuclear proteins, and the increased expression of some
      genes, may occur within a few hours or even minutes of irradiation. This would be
      sufficiently quick to explain the phenomenon of induced radioresistance although
      the precise mechanism, whether by repair, cell cycle control or some other
      process, remains yet undefined.

PMID- 8146327
TI  - A specific DNA-binding protein activated by ionizing radiation in normal cells
      and constitutively present in ataxia telangiectasia cells.
AB  - Exposure of mammalian cells to ionizing radiation gives rise to a complex series
      of changes. This response is characterized by the induction of a variety of genes
      and the activation of pre-existing proteins. We describe here activation of a
      specific DNA-binding protein by ionizing radiation. The response was dose
      dependent and specific for ionizing radiation. The binding factor appears to be
      normally present in the cytoplasm and responds to radiation by translocation to
      the nucleus, or is activated within the nucleus by an unknown mechanism. The
      radiation-induced activation of this protein appears to be mediated through a
      protein kinase C-associated pathway. A DNA-binding factor recognizing the same
      binding motif was found to be abnormally distributed in cells from patients with
      the human genetic disease, ataxia telangiectasia. The protein was constitutively
      present in the nucleus and the cytoplasm of ataxia telangiectasia cells and did
      not respond to radiation.

PMID- 8146328
TI  - Low doses of neutrons induce changes in gene expression.
AB  - Studies were designed to identify genes induced in fibroblasts after exposure to
      low-dose neutron radiation but not after gamma rays. Our past work had shown
      similar modulation of transcripts for alpha-tubulin, beta- and gamma-actins,
      ornithine decarboxylase and interleukin 1 after exposure to either neutrons or
      gamma rays. However, differences in the expression of beta-protein kinase C and c
      fos genes were observed, with both being induced after exposure to gamma rays but
      not neutrons. Recently we have identified two genes that are induced after
      exposure to neutrons but not gamma rays: Rp-8 (a gene associated with apoptosis)
      and the long terminal repeat (LTR) of the human immunodeficiency virus (HIV).
      Induction of Rp-8 mRNA was demonstrated in Syrian hamster embryo (SHE)
      fibroblasts and was found to be induced in cells exposed to neutrons administered
      at low (0.005 Gy/min) and high dose rate (0.12 Gy/min). No induction of other
      genes associated with apoptosis such as Rp-2, bcl-2 and Tcl-30 was observed. The
      induction of transcription from the LTR of HIV was demonstrated in HeLa cells
      bearing a transfected construct of the chloramphenicol acetyl transferase (CAT)
      gene driven by the HIV-LTR promoter. Measurements of CAT activity and CAT
      transcripts after irradiation demonstrated an unresponsiveness to gamma rays over
      a broad range of doses (0.1-3 Gy). Twofold induction of the HIV-LTR was detected
      after exposure to neutrons (0.48 Gy) administered at low (0.05 Gy/min) but not
      high (0.12 Gy/min) dose rates. Ultraviolet-mediated HIV-LTR induction, however,
      was inhibited by exposure to low-dose-rate neutron irradiation. These results are
      interesting in light of reports that Rp-8 is induced during apoptosis and that
      HIV causes apoptosis.

PMID- 8146329
TI  - The regulation of GRP78 and messenger RNA levels by hypoxia is modulated by
      protein kinase C activators and inhibitors.
AB  - In this study, we have shown that steady-state levels of glucose-regulated 78 kDa
      (GRP78) protein and messenger RNA increase during a 5-h exposure to 0.02% oxygen.
      This increase in GRP78 protein and mRNA induced by hypoxia can be abolished by a
      1-h pretreatment of cells before hypoxia with the protein kinase C (PKC)
      inhibitors staurosporine and H7 at concentrations at which the drugs themselves
      do not cause cytotoxicity. Although all studies using protein kinase inhibitors
      must be interpreted with caution, staurosporine and H7 have been shown to be
      potent inhibitors of PKC activity, suggesting a role for PKC in mediating the
      transcriptional regulation of GRP78 by hypoxia. Further support for PKC in
      regulating GRP78 gene expression by hypoxia stems from gel-mobility shift studies
      in mixtures of nuclear extracts from aerobic or hypoxic cells with a 36 bp region
      of the GRP78 promoter (-170 to -135). Binding of this factor could be inhibited
      by pretreating cells with the PKC inhibitor staurosporine before hypoxia or
      activated by treating cells with the PKC-activating phorbol ester TPA. These data
      suggest that activation of this hypoxia-responsive factor is sensitive to oxygen
      levels and seems to be mediated through a PKC signal transduction pathway.

PMID- 8146330
TI  - Cyclin expression and G2-phase delay after irradiation.
AB  - Many studies have demonstrated the effect of oncogene transfection on the
      radiation sensitivity of primary rat embryo fibroblasts. Our results indicate
      that transformation by H-ras plus v-myc oncogenes confers radiation resistance to
      a much greater extent than transformation by either gene alone. We have further
      shown that the radioresistant phenotype is accompanied by a prolonged G2-phase
      delay. This is consistent with the hypothesis that the extent of this delay is an
      important determinant of radiation sensitivity. The study of cyclin expression
      during the progression of cells through G2 and M phase after irradiation has also
      revealed several possible mechanisms for induction of G2-phase arrest. Control of
      cyclin B levels was seen both at the mRNA level as evidenced by decreased cyclin
      B mRNA expression after irradiation in the S phase, and at the protein level as
      demonstrated after irradiation in G2 phase. It remains to be determined how these
      mechanisms might be differentially regulated in radioresistant and sensitive
      cells.

PMID- 8146331
TI  - Isolation of an X-ray-responsive element in the promoter region of tissue-type
      plasminogen activator: potential uses of X-ray-responsive elements for gene
      therapy.
AB  - Tissue-type plasminogen activator (t-PA) was induced over 50-fold after X
      irradiation in radioresistant human melanoma cells (Boothman et al., Cancer Res.
      51, 5587-5595, 1991). Activities of t-PA were induced 14-fold in ataxia
      telangiectasia, 9-fold in Bloom's syndrome and 6-fold in Fanconi's anemia cells,
      compared to normal human fibroblasts (Fukunaga et al., Int. J. Radiat. Oncol.
      Biol. Phys. 24, 949-957, 1992). X-ray-inducible synthesis of the protease, t-PA,
      may play a role(s) in damage-inducible repair processes in mammalian cells,
      similar to the SOS repair systems in lower eukaryotes and prokaryotes. DNA band
      shift and DNase I footprinting assays were used to determine binding if
      transcription factors to a previously unknown X-ray-responsive element (XRE) in
      the t-PA promoter. The major goals of our research with XREs are to understand
      (a) which transcription factor(s) regulates t-PA induction after X rays, and (b)
      the role(s) of t-PA in DNA repair, apoptosis or other responses to X rays. The
      purpose of this paper is to discuss the potential use of an XRE, such as the one
      in the t-PA promoter, for gene radiotherapy. Several gene therapy strategies are
      proposed.

PMID- 8146332
TI  - The survival of asynchronous V79 cells at low radiation doses: modeling the
      response of mixed cell populations.
AB  - We have observed that when a single linear-quadratic (LQ) function is used to fit
      the radiation survival response of an asynchronously dividing population of V79
      cells, a consistent misfit occurs at low doses. The data can be better described
      by fitting the low-dose and high-dose ranges separately, and there is evidence of
      a two-component response. The most obvious explanation is that we may simply be
      seeing the response of subpopulations of cells of different radiosensitivity:
      sensitive G1-, G2- and M-phase cells and resistant S-phase cells. The cell
      sorting assay for cell survival which we have used in these studies may thus be
      providing sufficient accuracy to resolve these subpopulations, not previously
      seen in conventional survival measurements. An alternative explanation is that
      the linear-quadratic function may be inappropriate for accurate description of
      the radiation survival response at low dose, at least for these cells. To test
      this hypothesis we have used three other models to fit the data: the single-hit
      plus multi-target (SHMT) model and the two-parameter repair-misrepair (RMR) model
      both yielded inferior fits to the asynchronous survival data; the three-parameter
      RMR model provided an improved fit to the data. The best fit, however, was
      obtained using a two-population LQ model, which suggested approximately equal
      numbers of sensitive and resistant cells. When the survival response of tightly
      synchronized G1/S-phase cells was measured using the cell sorting assay, no
      substructure was observed. This offers strong support to the hypothesis that the
      substructure observed in the asynchronous survival response is due to
      subpopulations of cells of different, cycle-dependent radiosensitivity.

PMID- 8146333
TI  - The response of a human tumor cell line to low radiation doses: evidence of
      enhanced sensitivity.
AB  - The survival of asynchronous, exponentially growing DU-145 human tumor cells was
      measured after single doses of X rays in the dose range of 0.05-4 Gy using the
      cell sorting assay. When the response was modeled with the linear-quadratic (LQ)
      equation, a good fit to the data was observed for dose levels above 1 Gy;
      however, a region of enhanced sensitivity was observed at doses less than this.
      One possible explanation of this low-dose substructure is that a small, sensitive
      subpopulation of cells is selectively killed at low doses. Modeling of the
      radiation response with a two-population LQ model suggests that for these data
      this explanation is unlikely. Another possibility is that the whole cell
      population is initially hypersensitive, becoming radioresistant as damage is
      sustained by the cell. Conceivably this radioprotective mechanism could act in
      one of two ways. The cell could move from a radiation-sensitive to a radiation
      resistant state by a continuous function of dose, or alternatively, only after a
      sufficient accumulation of damage, i.e. a "triggering dose." Both of these
      possibilities have been explored in the results of fitting two "induced
      resistance" models.

PMID- 8146334
TI  - The response of Chinese hamster V79-379A cells exposed to negative pi-mesons:
      evidence that increased radioresistance is dependent on linear energy transfer.
AB  - Chinese hamster V79-379A cells exhibit low-dose hypersensitivity to 250 kVp X
      rays followed by an increased radioresistant response over the dose range 0.5-1
      Gy. This phenomenon is not seen with neutrons (Marples and Joiner, Radiat. Res.
      133, 41-51, 1993). It was therefore postulated the induction of radioresistance
      might develop as a response to a cellular event(s) which predominates after low-
      and not high-LET radiation. To test this hypothesis, we measured the survival
      response of V79-379A cells exposed to pions. Clonogenic survival was assessed for
      cells irradiated in the Bragg peak (35 keV/microns) and plateau region (10-20
      keV/microns) of the beam, using an automated microscope (DMIPS cell analyzer). As
      expected, peak pions were found to be more effective per unit of dose at killing
      cells than plateau pions. The survival curve for cells irradiated in the plateau
      of the pion beam was found to incorporate a region of low-dose hypersensitivity
      and increased radioresistance, the effective D0 was dose-dependent, ranging from
      3.5-5. This was not seen with peak pions, where the effective D0 was, on average,
      constant reflecting a single-exponential survival curve. Fitting the data with an
      induced repair model indicates that the phenomenon of increased radioresistance
      is almost certainly dependent on LET.

PMID- 8146335
TI  - DNA damage as the cause of ionizing radiation-induced gene activation.
AB  - Tyrosine kinases have been shown to be activated by both UVA and UVC light and
      gamma irradiation. For UV exposure, a non-DNA target has been proposed. Here the
      possibility of a non-DNA target for ionizing radiation is examined. A comparison
      of the fluence/dose to which the cells were exposed to elicit the response
      indicates that three orders of magnitude greater numbers of potentially damaging
      events occur after UVC exposure than after gamma irradiation. Thus, while the
      involvement of a non-DNA target by UVC is possible, the probability of "hits" on
      such targets by ionizing radiation events is remote. The levels of intracellular
      endogenous oxidation damage are compared to those produced by ionizing radiation.
      This indicates that an oxidation product which is rapidly repaired and which is
      therefore present at low endogenous levels, such as the DNA single-strand break,
      is a candidate lesion for signal induction.

PMID- 8146336
TI  - Do low doses of radiation induce a response modulating induction or repair of DNA
      single-strand breaks?
AB  - Many recent reports have indicated interesting structure in the low-dose region
      of survival curves for mammalian cells (e.g., variations in the effects of
      oxygen, high-order modulation of the dose-response function, induction of repair,
      activation of protein-modifying enzymes, influences of cytokines, etc.). Since we
      have recently identified and corrected several problems causing variability in
      the results of the alkaline elution methodology, we felt that it was important to
      investigate the formation and repair of single-strand breaks (SSBs) in this low
      dose region. To date we have asked three questions relevant to the structure
      features noted above: (1) Is the dose response linear at very low radiation
      doses? (2) Is repair of SSBs complete? (3) Do low "priming" doses of radiation
      induce subsequent variations in the sensitivity, or rate or extent of repair? To
      date, we have found no basis in SSB induction and repair for the interesting
      substructure noted in the survival responses above. At doses from 0.25 Gy to 4 Gy
      in air, no significant deviations from a linear dose response were observed, and
      a "priming" dose of 2 Gy has a minimal effect on subsequent sensitivity of SSB
      formation. Repair of SSBs appears complete at clinical doses of 2 Gy, but
      substantial unrepaired SSB damage remains 1 h after doses (11 Gy) corresponding
      to a surviving fraction of 0.01. No significant change in repair of SSBs at 4 h
      after a 2-Gy priming dose has yet been determined.

PMID- 8146337
TI  - Chromosomal adaptive response in human lymphocytes.
AB  - It has been almost a decade since the initial report of Olivieri et al. (Science
      223, 594-597, 1984) on the phenomenon they termed "adaptive response of human
      lymphocytes to ionizing radiation." Although a number of reports have appeared
      since then, our understanding of this response is still incomplete. In this
      paper, the author presents an analysis of the area using published data in the
      literature as well as unpublished data from the author's laboratory. Most of the
      data come from measurements of the effects of low-dose radiation on chromatid
      type aberrations induced in late S/early G2 phase cells. Exposure of lymphocytes
      to low doses of ionizing radiation can affect a certain fraction of aberrations
      induced by a subsequent high dose. Chemicals have been substituted for ionizing
      radiation as either inducers or challenging agents; however, their use has not
      provided specific information about inducing signals or target lesions. The
      working hypothesis in studies on adaptive response is that a repair activity is
      induced that acts on lesions in DNA. Although there is promising evidence that
      new and/or altered synthesis of proteins is required to observe reductions in
      aberrations, the gap between hypothesis and evidence is still wide. Co-ordinate
      analysis of different end points in individual cells should help to close this
      gap. While an adaptive response can be induced under a range of conditions, there
      is no good explanation for the inter/intradonor variability observed. The
      contributors to this variation need to be identified.

PMID- 8146338
TI  - Dose-rate effect for DNA damage induced by ionizing radiation in human tumor
      cells.
AB  - The effect of dose rate on clonogenic cell survival and DNA double-strand breaks
      (DSBs) has been examined in a human bladder carcinoma cell line, RT112, treated
      with ionizing radiation. Cell survival changed markedly over the range of dose
      rates used (0.01-1.28 Gy/min) with the curves becoming shallower and straighter
      as the dose rate was lowered. Similarly, the number of DSBs measured by pulsed
      field gel electrophoresis (PFGE) immediately after irradiation varied with dose
      rate. Fewer DSBs were detectable after low-dose-rate irradiation. However, when a
      4-h repair period was allowed after irradiation, cells treated at all dose rates
      exhibited approximately the same amount of damage. The final level of unrejoined
      DSBs, as detected by PFGE, therefore does not correlate with cell survival at
      different dose rates.

PMID- 8146339
TI  - Survival curves with shoulders: damage interaction, unsaturated but dose
      dependent rejoining kinetics or inducible repair of DNA double-strand breaks?
AB  - Double-strand breaks (DSBs) are considered as critical lesions for radiation
      induced cell killing. Two processes, identified by the rejoining kinetics of DNA
      DSBs induced in yeast at radiation doses which are also applied in survival
      studies, can lead to survival curves with shoulders: firstly, "DSB interaction"
      when repair time is unrestricted, and secondly, a biphasic and unsaturated DSB
      rejoining, where the fractions of the two rejoining components are dose-dependent
      and repair time is restricted. Thus the unsaturated rejoining kinetics of DSBs is
      not in contradiction to the observation of survival curves with shoulders. While
      these two mechanisms are derived from studies on cells kept under nongrowth
      conditions during postirradiation incubation, experiments are reviewed which were
      designed to study inducibility of DSB rejoining. Some of these studies suggest
      that rejoining of DSBs under growth conditions may include an inducible process.

PMID- 8146340
TI  - [Intracranial meningiomas].
AB  - The author excised an intracranial meningioma from 28 patients, 17 women and 11
      men, between 7 and 78 years of age, from 1974 to 1992. The tumor was located in
      the olfactory groove in 4 patients, in the cerebral convexity in another 4, in
      the falx in 8 (3 in the frontal and 5 in the parietal region). In 6 patients, the
      meningioma was found in the inner one third and in 1 in the middle third of
      sphenoid; in 1, in the clivus, in 1 in the petrous bone; in 2 patients the tumor
      was located in the tubercle of the sella turcica and in another patient it was in
      the cerebello-pontine angle. Total resection of the meningioma was accomplished
      in 16 patients (57.1%) because the tumor was in an accessible area. The tumor
      recurred in one patient, who died 5 years post operatively. In 8 (28.5%) of 12
      patients in whom subtotal resection was done, post operative radiation was used,
      and in 3 of them recurrence occurred in less than 5 years after completion of
      treatment and in one, in less than 10. In 3 of the remain 4 patients, in whom
      subtotal resection was done but were not followed by radiation therapy,
      recurrence also occurred before 5 years post surgery, and in 1 patient at the end
      of 5 years.

PMID- 8146341
TI  - [Phacoemulsification. Towards a cataract surgery without sutures].
AB  - The surgeon presents the results of the first phacoemulsification procedures he
      performed. The procedure includes capsulorhexis and phacoemulsification within
      the bag in the posterior segment. This technique results in safe fixation of the
      intraocular lens implant in the bag.

PMID- 8146342
TI  - [The outpatient management of internal hemorrhoids by infrared photocoagulation].
AB  - Infrared photocoagulation is a new ambulatory therapy for 1st, 2nd and 3rd degree
      internal hemorrhoids. It is an effective method, comparable to others such as
      sclerotherapy or rubber band ligature. It is necessary to use multiple
      applications in several sessions in order to obtain good results. Patients with
      hemorrhoids grade IV are candidates for hemorrhoidectomy. The author did not
      observe minor nor serious complications with this new therapeutic modality. It is
      fast and easy to use by a single operator. The equipment is portable, easy to
      handle and long lasting, needing little maintenance. The anatomical results
      suggest that the progression of hemorrhoids and also, probably, surgery are
      prevented. Long-term follow up is necessary.

PMID- 8146343
TI  - [The sonographic diagnosis of hypertrophic stenosis of the pylorus].
AB  - The clinical records of 18 children were studied, between 15 and 60 days old.
      They were hospitalized due to vomiting and diagnosis of suspected pyloric
      hypertrophic stenosis (PHS). The sonography confirmed the diagnosis in 8
      children, by the thickening of the muscular layer and enlargement of the pyloric
      canal. The surgery (pyloromyotomy) ratified the diagnosis in all 8 children. They
      all were in good health after being operated.

PMID- 8146344
TI  - [The usefulness of Doppler in evaluating heart murmurs].
AB  - In two hundred and two patients with heart murmurs, the diagnosis obtained
      utilizing the physical exam were compared with the diagnosis arrived by
      echocardiography and color Doppler ultrasound. The comparisons revealed
      improvements in specificity with the utilization of echocardiography and color
      Doppler ultrasonography. It is concluded that these techniques represent a
      significant improvement in our diagnostic capabilities. The problems of
      overdependence in the ultrasound technique and the current loss of physical
      diagnosis skills is recognized.

PMID- 8146345
TI  - [Percutaneous endoscopic gastrostomy. An alternative for long-term enteral
      feeding].
AB  - This study shows that, in our environment, percutaneous endoscopic gastrostomy is
      feasible in most patients who need it, and at the same time it is a fast, safe
      and inexpensive procedure. The complication rate is low and most can be resolved
      rapidly medically or endoscopically. It also allows the placement of a permanent
      means for the administration of nutrients and for drainage of gastroduodenal
      secretions in those patients who warrant it.

PMID- 8146346
TI  - [The cardiovascular manifestations of Marfan's syndrome. A case report and review
      of the management].
AB  - The authors present the clinical history of a patient with Marfan's syndrome (MS)
      and aortic insufficiency, who expired at 22 years of age, in order to illustrate
      the clinical evolution and review the management of this problem. It is known
      that patients with MS and heart failure due to dilatation of the aortic annulus
      have an early mortality of almost 100%. The authors conclude that
      echocardiographic follow up of these patients is vital in their medical and
      surgical management and that the use of beta blockers is the best medical
      therapy, and that prophylactic surgery with composite graft (aortic valve and
      ascending aorta) gives the best survival rate.

PMID- 8146347
TI  - [The continent urinary reservoir].
AB  - Continent urinary reservoirs (CUR) have replaced ileum and colonic conducts as
      the best method for urinary diversion. The author present their experience with
      two patients in whom they fashioned a CUR in the Dr. Arnulfo Arias M.
      Metropolitan Complex using the ileocecal segment and part of the transverse colon
      (The Miami or Florida porch technique). They describe the clinical histories,
      surgical technique and the results obtained. They feel that the CUR has a large
      capacity, works at low pressure and is technically accessible. They consider it a
      good choice when urinary diversion is needed.

PMID- 8146348
TI  - [The analgesic and anti-inflammatory effects of Drymonia serrulata (Jacq.) Mart].
AB  - The authors experimentally demonstrated that an aqueous fraction of Drymonia
      serrulata (Jacq.) Mart. has peripheral, but not central, analgesic activity, and
      that it also has a dose-dependent anti-inflammatory activity at 24 and 96 hours.
      The experimental results indicate that the etnomedical use of this plant by the
      Guaymi Indians may have some scientific validity

PMID- 8146349
TI  - [An endodermal sinus tumor of the ovary. A case report].
AB  - The authors present the clinical history of a 15-year-old young woman, student,
      from David, Chiriqui, who complained of menstrual irregularities associated with
      the sensation of a mass in the right iliac fossa. Exploratory laparotomy revealed
      a right ovarian tumor, which was totally resected. The histopathological
      examination showed an endodermal sinus tumor, stage one, in the right ovary. The
      patient received four cycles of cytotoxic i.v. therapy every 3 weeks, after
      surgery, with vinblastine 6 mg/m2 body surface (B.S.) on days 1 and 2, bleomycin
      15 u daily for 5 days, cisplatin 20 mg/m2 B.S. daily for 5 days, plus hydration
      with normal saline (5 to 6 l/day). Follow up studies with abdominal and pelvic
      sonograms, chest x-ray, feto protein and physical examination have not shown
      evidence of tumor activity 36 months after diagnosis.

PMID- 8146350
TI  - [The nutritional evaluation of cooking fats and oils].
AB  - Fatty acids content of locally obtained margarines, shortenings and cooking oils
      from businesses in Panama were determined by gas chromatographic method. The
      results found show that all of these oils have a high nutritional value, because
      of their high unsaturated fatty acid content. The soya oil group is characterized
      by its high content of linolenic acid (w3), for this reason they are preferably
      recommended as edible oils. Margarines were classified as "saturated" (high in
      palmitic acid) and "unsaturated" (high in linoleic acid). Saturated margarines
      are not very recommendable as edible fats since the high palmitic acid content is
      a hypercholesterolemic agent. The majority of the shortenings are also rich in
      palmitic acid.

PMID- 8146351
TI  - [Helicobacter pylori at Hospital Santo Tomas].
AB  - We studied the incidence of infection with Helicobacter pylori in Panamanians
      with chronic dyspepsia, gastric or duodenal ulcer, gastritis or gastric cancer.
      The histopathology was positive in 54 (81%) of 66 patients; the urea test was
      positive in 52 (82.5%) of 63 cases; the impromptu was positive in 51 (79.6) of 64
      patients; the endoscopic examination was positive in 64 (82.9%) of 77
      examinations.

PMID- 8146352
TI  - [Experience with amlodipine (Norvasc) in the management of arterial
      hypertension].
AB  - The authors report the results of therapy with amlodipine in 20 patients with
      mild or moderate hypertension (diastolic pressure between 95 and 115 mmHg).
      Amlodopine was administered in a dose of either 5 or 10 mg once a day for 12
      weeks. None of the patients had a history of congestive heart failure. Eleven
      patients were men between 27 and 89 years of age (average age was 52.6 years).
      There was a significant decrease in systolic blood pressure (from 161 to 141 mm
      Hg or -12.4%) and in diastolic blood pressure (from 103 to 86 mm Hg or -16.5%).
      Heart rate remained between 78 and 77 beats per minute. Only one patient
      experienced palpitations and two complained of mild, transient giddiness while on
      this therapy.

PMID- 8146353
TI  - [The presence of genital mycoplasmas in women of reproductive age].
AB  - The authors examined 70 original samples obtained from 70 women seen at the Nuevo
      Veranillo Community Health Center because of suspected Mycoplasma infection. 23
      (33%) of the cultures were positive for Mycoplasma. The microscopic and chemical
      characteristics identified 3 (13%) as Ureaplasma urealyticum, 9 (39%) were
      Mycoplasma hominis and 11 (48%) were positive for both organisms. The rate of
      positive cultures for Mycoplasma was high, which could be an important finding
      since these organisms are associated to a variety of pathologic conditions in
      adults of both sexes, in pregnant women and in their offspring.

PMID- 8146354
TI  - [Interventional procedures in the upper urinary tract].

PMID- 8146355
TI  - [Diagnostic imaging of aortic dissection].

PMID- 8146356
TI  - [Subarachnoid hemorrhage: assessment in the acute phase with angiography, with
      high-resolution magnetic resonance (angio-MR)].
AB  - Previous reports demonstrated that Magnetic Resonance Angiography (MRA) is a
      reliable means of diagnosing intracerebral aneurysms. However, in these early
      studies MRA was performed in patients with cerebral aneurysms already proved by
      intraarterial angiography. Our study was aimed at investigating the clinical
      feasibility and the diagnostic accuracy of high-resolution MRA in patients with
      acute subarachnoid hemorrhage. Twenty-five patients (15 women, 10 men) with CT
      diagnosis of subarachnoid hemorrhage were prospectively examined with high
      resolution MRA within 24 hours of bleeding. All patients underwent intraarterial
      digital subtraction angiography (IA DSA) immediately after MRA examination. MRA
      studies were performed with a 1.5-T unit. MRA examinations of the cerebral
      vessels consisted of axial excitation of two 50-mm volume slabs, with 25%
      overlap, covering the cerebral circulation from the vertebro-basilar junction to
      the pericallosal artery. Pulse sequence variables were optimized to reduce voxel
      size (0.62 x 0.62 x 0.78) and to increase spatial resolution (160-mm FOV, 256 x
      256 matrix, 0.78-mm slice thickness) while keeping S/N ratio high. The maximum
      intensity projection (MIP) reconstruction algorithm was used. The examination
      lasted nearly 20 minutes. Four MRA examinations (16%) were considered inadequate
      for diagnosis because of motion artifacts. High-resolution MRA detected 20 of 21
      aneurysms in 17 patients, with 1 false positive and 1 false negative. Two
      patients had multiple aneurysms, 2 and 4 respectively, all of them detected by
      MRA. No cause of subarachnoid hemorrhage was found by IA DSA in 4 patients, while
      MRA studies were considered negative in 3 patients. Nineteen aneurysms were
      surgically clipped, while 2 basilar artery aneurysms were occluded by
      intravascular treatment. MRA and DSA findings were compared with surgical
      findings. Relative to IA DSA, MRA exhibited 95% sensitivity and 95% specificity.
      Aneurysm size ranged 2-10 mm: the smallest aneurysm detected by MRA was 2.5 mm.
      Anatomical and morphological agreement between MRA and IA DSA was excellent, with
      only slight MRA underestimation of the aneurysm size in 25% of cases and
      overestimation in 15% of cases. The aneurysm neck was shown by MRA in 60% and by
      IA DSA in 81% of cases. High-resolution MRA proved to be especially useful in
      complex anatomical sites where the direction of the aneurysm could be clearly
      demonstrated through the accurate selection of the appropriate projection angle
      and the careful examination of direct axial images.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8146357
TI  - [Critical review of the diagnostic protocol in patients with head injury].
AB  - The results of a retrospective review of the conventional radiographs performed
      on head injury patients are reported. Skull radiography findings were compared
      with clinical symptoms and CT results, when CT was performed, to investigate the
      presence of intracranial lesions. The radiographs of 2,285 adult patients of both
      sexes were evaluated: skull fractures were observed in 21/2,285 patients (0.9%)
      only. CT was positive for an intracranial lesion in 18 of 21 patients (85.71%).
      Clinical symptoms were divided into three groups according to lesion severity and
      to neurologic impairment. 979 patients were asymptomatic and 1,306 were
      symptomatic: 1,114 patients were included in group I, their symptoms being
      nausea, vomit and loss of consciousness for less than ten minutes, 124 were
      included in group II (epistaxis and loss of consciousness for more than 10
      minutes) and 68 were included in group III (coma and focal neurologic signs). All
      the patients in groups II and III and 30 patients in group I were submitted to CT
      -222 CT exams on the whole. Thirty-five patients in group III and 9 in group II
      had an intracranial lesion on CT, while CT findings were normal in all group-I
      patients. Thus, we conclude that the presence of a skull fracture is not always
      correlated with the presence of intracranial lesions. The latter are more likely
      to be correlated with clinical symptoms, especially coma and neurologic
      impairement. Therefore, the higher value is confirmed of the clinical examination
      than of conventional radiographs in head injury patients.

PMID- 8146358
TI  - [Computed tomography in acute inflammation of the orbit].
AB  - Acute orbital infection, which is usually secondary to sinusitis, requires prompt
      diagnosis and timely treatment to prevent the infection from spreading and to
      avoid severe complications, such as osteomyelitis, orbital and cerebral
      abscesses, meningitis and cavernous sinus thrombophlebitis. Fifteen young
      patients with orbital cellulitis were examined: they were 13 men and 2 women,
      whose mean age was 23 years, with orbital cellulitis secondary to fronto
      ethmoidal sinusitis (10 cases), to maxillary sinusitis (4 cases) and to
      craniofacial trauma (1 case). On the basis of CT findings the patients were
      divided into two groups according to whether the inflammatory process involved
      the preseptal (4 cases) or the postseptal (11 cases) space; postseptal cellulitis
      was classified as orbital cellulitis and subperiosteal abscesses. The site of the
      inflammatory process must always be accurately located because orbital septum
      integrity does affect treatment choice, which in our series was medical in
      preseptal cellulitis and always surgical in subperiosteal abscess. After
      describing the CT patterns of cellulitis and its possible complications, the
      authors emphasize the role of CT as the method of choice to confirm clinical
      diagnosis and to demonstrate the site, the extent and the complications of acute
      orbital cellulitis.

PMID- 8146359
TI  - [Value of magnetic resonance in the staging of non-small-cell lung carcinoma].
AB  - In the last six years, 544 consecutive patients with nonsmall-cell bronchogenic
      carcinoma were studied with MRI. MR results were compared with surgical specimens
      and pathologic findings. Both TNM classification and ATS nodal mapping were
      considered. Local tumor extent (T parameter) was correctly identified in 67.2% of
      cases, understaged in 19.4% and overstaged in 13.4%. Lymph node metastases (N
      parameter) were adequately assessed in 55.5% of cases, understaged in 20.3% and
      overstaged in 24.2%. Considering two groups of patients, the first one with early
      stage disease (T1-T2, N0-N1) and the second one with advanced stages (T3-T4, N2
      N3), MRI exhibited 84.6% overall accuracy, 57.3% sensitivity and 93.7%
      specificity for the T parameter and 72.3% accuracy, 65.2% sensitivity and 75.1%
      specificity for the N parameter. In conclusion, MRI did not provide the expected
      results in the staging of nonsmall-cell bronchogenic carcinoma, but improvement
      will probably be achieved with technological evolution.

PMID- 8146360
TI  - [Metachronous tumors of the breast. Mammographic findings].
AB  - In breast carcinoma patients the risk to develop a second lesion in the
      contralateral breast is two to six times higher than in control subjects. The
      second lesion is called metachronous and classified among bilateral breast
      cancers. This kind of lesion affects the patients who were mastectomized for
      breast carcinoma; it may be a primary lesion, when the histologic type is
      different from that of the first breast cancer or secondary, when the histologic
      type is the same as that of the first tumor and the second lesion is therefore a
      metastasis. This study was made to assess the incidence of metachronous lesions
      and the average time between the first and the second tumor and to investigate
      the value of mammographic followup. We selected 375 patients who had undergone
      mastectomy for different histologic types of breast carcinoma and examined the
      contralateral breast with mammography 6 months after surgery and then every 12
      months, January 1990 through January 1992. Mammography showed metachronous
      lesions in 23 cases: 15 infiltrating ductal carcinomas, 6 infiltrating lobular
      carcinomas and 2 in situ carcinomas, the latter with histologic confirmation in
      the patients operated on for benign breast lesions. The incidence of metachronous
      tumors was 6%, including both the primary and the metastatic lesions; the average
      time between the first and the second tumors was 20 months. Mammography allowed
      metachronous lesions to be diagnosed in a very early stage, much earlier than in
      other studies not including mammography. Prognosis is definitely improved by the
      early diagnosis of primary breast cancer, when no metastatic spread is present,
      and also in case of primary metachronous lesions, which are very uncommon.

PMID- 8146361
TI  - [Breast lymphoma].
AB  - Primary malignant lymphomas of the breast are uncommon findings, representing
      0.12% to 0.53% of all breast cancers. Secondary lymphomas are also uncommon, but
      they make the most frequent metastatic breast cancers. From January 1989 through
      December 1992, at the Department of Radiology of the University of Perugia, the
      authors observed 6 cases of breast lymphoma--1 primary and 5 secondary lesions-
      in women 52 to 67 years old (average 60 years). The only primary lymphoma was
      unilateral, multiple and localized on the right side; the secondary ones were
      diffuse and bilateral in 4 cases and unilateral and nodular in 1 case. The
      clinical findings were always suggestive of a malignant lesion and so were the
      mammographic and US findings in 4 diffuse lesions--3 bilateral and 1 unilateral
      cancers; in both the primary lymphoma and the secondary nodular lymphoma
      mammography showed benign patterns. Diagnosis was made in all cases following
      biopsy or resection of the breast mass; all the lymphomas were of the non
      Hodgkin's type. The authors report on the major clinical, mammographic and US
      features of this unusual disease and include a short review of the relative
      literature.

PMID- 8146362
TI  - [Renal arteries: angiography with TOF 3D magnetic resonance with and without
      contrast media (Gd-DTPA)].
AB  - This work was aimed at investigating the value of Gd-DTPA to demonstrate distal
      renal artery branches with 3D TOF Magnetic Resonance angiography (MRA). Ten
      volunteers and two patients with proximal-distal renal artery stenoses were
      studied with MRA; all subjects were studied before and after Gd-DTPA. MRA was
      performed with a 1.5-T superconductive magnet (Magnetom Siemens); the FISP 3D
      sequence was used with the following setting: FA 25 degrees, TR 40 ms, TE 6 ms,
      slice thickness 64 mm with 64 partitions and MA 256 x 256. This setting was not
      changed from pre- to post-contrast scans. The images acquired on the z axis were
      rotated, according to the MIP, on the axial and the sagittal axes, from 0 degrees
      to 180 degrees, with a 15 degrees step. 0.2 ml/kg of Gd-DTPA were injected as
      bolus during 3D acquisitions; the injection was started half-way through
      acquisition. To evaluate and compare pre- and post-contrast MRA images, the
      signal-to-noise (S/N) ratio and the demonstration of the various renal artery
      segments were studied. Average S/N ratio was 2.3 in the right renal artery and
      2.1 in the left renal artery on pre-contrast MRA images, while it was 0.9 in the
      left renal artery and 0.8 in the right renal artery on post-contrast MRA images.
      These differences were statistically significant (p < 0.01). As for the
      demonstration of the distal segments and of the bifurcations, enhanced MRA was no
      better than unenhanced MRA. As for the demonstration of distal segment stenoses,
      enhanced MRA proved no better than unenhanced MRA in both patients. To conclude,
      in our experience MRA after Gd-DTPA failed to allow the systematic demonstration
      of the distal segments and of the bifurcations of the renal arteries.

PMID- 8146363
TI  - [Color Doppler ultrasonography versus angiography in leg aneurysms].
AB  - The authors compared color-Doppler US with angiographic findings in the study of
      peripheral lower limbs aneurysms. Twelve cases were observed over a 2-year period
      of time. In each case, the combination of B-mode and color-Doppler US permitted
      the accurate evaluation of the aneurysm and of the possible compression of
      adjacent vessels. Angiography, which was considered the gold standard, detected
      only 8 of 12 cases; in 3 of 8 cases, the actual diameter of the aneurysm was
      under estimated. The simultaneous visualization of vessel wall and of
      intraluminal blood flow proved color-Doppler US to be superior to the gold
      standard in these cases. The authors conclude that color-Doppler US may become
      the new reference standard in the diagnosis and follow-up of peripheral
      aneurysms.

PMID- 8146364
TI  - [Reproducibility of Doppler ultrasonography in the study of hepatic blood flow].
AB  - The reproducibility of hepatic blood flow measurement with pulsed Doppler US was
      assessed in 6 healthy volunteers. All subjects underwent two different study
      sessions and were examined by three different operators after overnight fasting.
      Each operator was blind to his measurements. Hepatic arterial and portal venous
      blood flow and hepatic arterial maximum velocity were measured; resistive index
      (RI), pulsatility index (PI) and hepatic perfusion index (HPI) were calculated.
      Each measurement was repeated three times per session. The data from repeated
      measurements were analyzed with the analysis of variance (ANOVA) method to assess
      the intra- and intersubject variations for each variable. The Scheffe test was
      used to evaluate intra- and interobserver variations. Significant differences
      among the 6 examined subjects were found for all the variables measured, except
      for hepatic arterial maximum velocity. The same subject exhibited significant
      differences in mean velocity of the main portal vein trunk and of its right
      branch, in maximum hepatic arterial velocity, RI, portal vein section area and
      blood flow. No significant interobserver variation was observed in the same
      session and no intraobserver variation detected for all the measurements
      performed in different sessions. Thus, we conclude that pulsed Doppler US is a
      repeatable method for measuring hepatic blood flow and may therefore be useful to
      detect changes in hepatic perfusion.

PMID- 8146365
TI  - [Doppler ultrasonography assessment of the inferior mesenteric artery.
      Feasibility study and definition of morphologic and flowmetric characteristics].
AB  - The conventional and Doppler US assessment of the inferior mesenteric artery has
      not been reported in the literature to date. In the present study, the
      feasibility of Doppler US of the inferior mesenteric artery was prospectively
      investigated in 112 consecutive nonselected patients; the corresponding
      morphological features (size and vessel course) and Doppler flowmetry (peak
      systolic, peak diastolic and mean velocities; pulsatility index) were defined. In
      32 patients (29%) neither conventional nor color-Doppler nor duplex imaging was
      possible. Of the extant 80 patients, in 65 (81%) all the three methods allowed
      the correct assessment of the inferior mesenteric artery; in 15 patients (19%)
      the results were suboptimal (poor US visualization, or inadequate Doppler
      flowmetry). In 33/80 patients, arterial blood flow was quantitatively assessed in
      1/min. As for the patients who underwent further diagnostic procedures--e.g., CT
      and angiography--a close correlation was demonstrated between the morphological
      and functional data obtained by Doppler US and the corresponding CT and
      angiographic features. The possibility of analyzing the inferior mesenteric
      artery with conventional and Doppler US, besides the celiac trunk and the
      superior mesenteric artery, should allow splanchnic circulation to be more
      completely assessed, thanks to information about normal hemodynamics (after a
      meal or in response to pharmacological treatments) as well as about the diseases
      known to affect intestinal perfusion--e.g., mesenteric ischemia.

PMID- 8146366
TI  - [Color Doppler ultrasonography in the identification and characterization of
      secondary focal lesions of the liver].
AB  - This study was aimed at assessing the potentials of color Doppler US in the
      detection of hepatic metastases by measuring changes in hepatic perfusion. Color
      Doppler US was performed on 40 patients with multiple metastatic lesions (mean
      theta: 3 cm). In each patient both smaller and bigger lesions were studied--80
      lesions on the whole. Differences in flow distribution (peritumoral or
      intratumoral) and the highest systolic peak flow velocity were investigated on
      color Doppler US scans. Hepatic arterial and portal venous blood flow measured in
      40 patients with hepatic metastases were compared with those in 40 healthy
      controls. The two groups were homogeneous relative to age, sex, height and
      weight. The ratio of hepatic arterial to total liver blood flow (Doppler
      perfusion index, DPI) and the ratio of hepatic arterial to portal venous blood
      flow (Doppler flow ratio, DFR) were calculated. Color flow US scans were obtained
      in 56 of 80 metastatic lesions. We observed peritumoral flow in 76% of the
      lesions, intratumoral flow in 6% and mixed peritumoral and intratumoral flow in
      18% of cases. The DPI and DFR values were significantly higher in the patients
      with liver metastases than in the control group. The changes in DPI and DFR
      resulted from an increase in hepatic arterial flow; no changes in portal venous
      blood flow were observed. These results suggest that Doppler measurements of
      hemodynamic hepatic changes may be of great value for the earlier detection of
      hepatic metastases.

PMID- 8146367
TI  - [Secondary solid neoplasms in young patients treated for lymphoproliferative
      diseases: computed tomography findings].
AB  - Diagnostic imaging still plays a key role in the follow-up of oncologic patients.
      In particular, in hemolymphoproliferative disorders, diagnostic imaging is used
      to differentiate the complications of integrated treatment from possible
      relapses. Integrated treatments have lengthened the survival of these patients
      and therefore such long-term complications as secondary--especially solid--tumors
      are now more frequently observed. We report on two such cases whose onset
      followed by 6 and 5 1/2 years the end of the initial treatment: the patients had
      been cured for acute lymphatic leukemia and Hodgkin's lymphoma. In the leukemia
      patient, CT and MRI demonstrated a large mediastinal mass, which had been an
      occasional finding at chest film. CT correctly diagnosed the mass and suggested
      extrapulmonary and extramediastinal localization, since fat cleavages were
      normal. MRI allowed better characterization of the mass which was isointense to
      muscle independent of TR. Disease relapse was excluded and surgery allowed the
      complete ablation of the ganglioneuroma. In the lymphoma patient, a left
      hypochondrium mass was supposed as an abdominal relapse from Hodgkin's lymphoma.
      CT allowed the correct diagnosis of gastric adenocarcinoma to be made on the
      basis of the mass multifocality and marked enhancement, of the infiltration of
      liver and hepatogastric ligament lymph nodes and finally of peritoneal
      involvement. Secondary solid tumors are no remote finding in the follow-up of the
      patients treated for lymphoproliferative disorders. Diagnostic imaging must allow
      the differential diagnosis especially from relapses and must use the techniques
      which are most capable of doing so.

PMID- 8146368
TI  - [Applications of digital radiology to pediatric uroradiology].
AB  - The authors report their 4 years' experience with a computerized digital
      radiographic system based on photostimulable phosphor plates which was used
      mostly in pediatric radiology. Major protection advantages were observed for
      uroradiology where high kV (90-95 kV) and very low exposure times (0.02-0.010s)
      were used. With this radiographic technique reduced exposure parallels increased
      graininess due to quantum mottle: the two variables must therefore be balanced
      not to decrease diagnostic accuracy. During our 4 years' experience, 368
      examinations were performed on pediatric patients: 252 micturition
      cystourethographs, 81 urograms and 35 retrograde pyelographs. None of these
      examinations needed to be repeated due to over/under-exposure and image quality
      was always high, in spite of a light "noise". Digital radiography in pediatric
      urology allows radiation dose to be reduced and high quality images to be
      acquired and is therefore likely to take over conventional radiologic techniques.

PMID- 8146369
TI  - [Percutaneous computed tomography-guided biopsy in spinal diseases].
AB  - The use of percutaneous spinal biopsy (PSB) is on the increase in the field of
      interventional radiology. From July 1990 to December 1992 in the Department of
      Radiology in the Istituto Ortopedico Rizzoli, 74 patients (50 men and 24 women,
      mean age: 47 years old) underwent CT-guided spinal biopsy. This study was aimed
      at evaluating the diagnostic capabilities and accuracy of CT-guided percutaneous
      biopsy, which is considered as a simple, reliable and definitive method for
      histopathologic diagnosis. In our case histories, the total average accuracy
      rate, which varies according to the involved segment and to the kind of lesion to
      be examined, was 86%; in 14% of cases the excised tissue proved insufficient for
      histologic diagnosis. By allowing the histopathologic diagnosis to be made, CT
      guided PSB proves a valuable technique to plan the treatment of primary/secondary
      neoplastic lesions or of inflammatory and dysmetabolic processes.

PMID- 8146370
TI  - [Computed tomography of the knee in forced varus and valgus positions to study
      the menisci].

PMID- 8146371
TI  - [Applications of the quality control program in diagnostic radiology.
      Confirmation of results, clinical and managerial benefits].
AB  - The Health Physics Department developed and implemented a QA program to test the
      X-ray equipment in Policlinico S. Orsola-Malpighi, Bologna, Italy. The program
      was aimed at achieving "total quality" in diagnostic radiology. To this purpose,
      suggestions were taken from: the code of practice of the leading international
      committees; our personal experience over several years in measuring and
      evaluating radiologic equipment and finally data relative to the maintenance
      procedures for radiologic equipment. The Integrated Quality Assurance Program
      (IQAP) manages two different quality control sub-procedures: the first one (QF)
      monitors equipment performance with a view to providing more pieces of diagnostic
      information and to reducing both patient and staff dose; the other one (QG) plans
      maintenance service to reduce running costs. QF included: i) practical tests for
      X-ray equipment; ii) analysis, interpretation and comparison of results; iii)
      tolerance limits. QG provided information on: i) inventory; ii) user-service
      relationship; iii) suitability of any corrective actions. The data relative to
      the last four years are reported in the text. The regular and correct use of this
      integrated protocol is very useful to monitor the factors affecting image quality
      and to improve diagnostic radiology. Finally, the protocol allowed us to plan our
      "yearly maintenance contracts" better and to save money on running costs.

PMID- 8146372
TI  - [In vivo dosimetry and radiographic confirmation in radiotherapy of Hodgkin's
      lymphoma].
AB  - In September 1991 a protocol for quality control of large shaped irradiation
      fields was started in our department. In vivo dosimetry with semiconductor
      detectors was used to measure the absorbed dose and patient positioning was
      checked with portal films weekly. First, we set a computed dosimetric system
      yielding dosimetric values in real time and allowing their easy storage. Then, we
      calibrated the diodes and determined the correction factors for each of them
      outside standard conditions. Entrance dose, exit dose and midline dose were
      measured in 62 patients undergoing supradiaphragmatic radiation therapy for
      Hodgkin's lymphoma. The exist dose was measured weekly to assess treatment
      repeatability. High agreement was observed between measured and calculated doses;
      repeatability was also high, since only 6% of exit dose measurements exceeded 5%
      of the first determination. In 33 patients portal films were obtained in the
      first treatment session, and thereafter weekly, to assess mispositioning relative
      to simulation (reproducibility) and from one session to another (repeatability).
      A small systematic error was detected in both longitudinal (x = -3 mm; SD = 3.7
      mm) and transverse (x = -2 mm; SD = 3.4 mm) directions. Statistically significant
      errors (> 6 mm) were observed in 14% of patients. Reproducibility was excellent.
      The protocol reported on in this paper not only helps avoid systematic dosimetric
      and/or positioning errors in the patients, but also helps identify the main
      causes of uncertainty and thus remove them.

PMID- 8146373
TI  - [Contribution of nuclear medicine to the diagnosis of silent adrenal masses].
AB  - The role of adrenal scintigraphy in the noninvasive characterization of silent
      adrenal masses was investigated in 40 patients. The mass had been detected by US
      or CT performed in the evaluation of non-malignant extra-adrenal diseases (25
      cases) or during staging or follow-up of a malignant extra-adrenal neoplasm (15
      cases). In all cases radio-cholesterol scintigraphy (74 MBq i.v. of 131I-6 beta
      iodomethylnorcholesterol in 19 cases; 11 MBq i.v. of 75Se-6 beta
      selenomethylnorcholesterol in 21 cases) was performed; in 7 cases also 131I-MIBG
      scan (18.5-37 MBq i.v.) was carried out. When compared with CT data,
      radiocholesterol scintigraphy (standard or after suppression with dexamethasone)
      showed: concordant uptake (increased uptake of radiocholesterol on the side of
      the adrenal mass) in 24/26 patients with adrenal cortical adenoma; discordant
      uptake (absent or decreased uptake on the side of the adrenal mass) in 12
      patients: 5 with adrenal metastases and 7 with non-adenomatous benign space
      occupying lesions (2 ganglioneuromas, 1 post-traumatic hemorrhagic lesion, 3
      adrenal cysts, 1 myelolipoma); indeterminate uptake (symmetric bilateral uptake)
      in 4 patients: 2 with a small adenoma, 1 with adrenal metastasis and 1 with a
      "false incidentaloma" (hepatic regenerative nodule). The results confirm the
      utility of radiocholesterol scintigraphy in demonstrating the benignity of
      adrenal lesions (particularly in identifying adrenocortical adenomas) and assess
      its place among the procedures used to characterize silent adrenal masses. The
      possible use of MIBG scintigraphy is also discussed.

PMID- 8146374
TI  - [Quantitative scintigraphic detection of 111In sources].
AB  - This paper reports on a quantitative scintigraphic method for 111In sources using
      counts from isoboundary regions of interest of source images. Accordingly, total
      counts from regions of the image excluding the counts below a given percentage of
      the maximum are recorded and attenuation correction is implemented using the
      Depth Independent Buildup Factor method which corrects the effects of Compton
      scattering on the transmission function of the photon flux leaving the source.
      The transmission function of both the 172 and the 247 keV photons of 111In was
      determined for a set of circular flat sources of varying diameter (33 to 111 mm),
      using counts recorded in isoboundary regions of interest of images of the sources
      placed in air and at various depths in water. The images were acquired using a
      gamma camera equipped with a parallel hole medium energy collimator. The
      influence of the isoboundary value on the shape of the transmission function was
      investigated, and thus the chosen isoboundary value was set to no more than 20%
      of the maximum count on the image. Two parallel and dimetrically opposed views
      were acquired to determine the unknown activity of the sources placed in a water
      phantom. This counting geometry was chosen to operate in conditions of depth
      independent of the source in the phantom. Our results show a high degree of
      accuracy, the experimental estimate of the activity obtained by using the counts
      in the regions of interest with the lowest isoboundary value exhibiting 4% error
      rate. The error rate increases with the increase in the isoboundary values. The
      method proved to be simple, practical and accurate. Moreover, it overcomes the
      problem of accurate estimation of sources size, a variable usually not known with
      sufficient accuracy in clinical scintigraphic studies.

PMID- 8146375
TI  - [Diagnostic imaging in a case of anterior sacral meningocele].

PMID- 8146376
TI  - [A case of lissencephaly].

PMID- 8146377
TI  - [Cystic neurinoma of the axilla. A case report].

PMID- 8146378
TI  - [Unusual benign lesion of the thoracic wall. Abrikossoff's myoblastoma.
      Diagnostic imaging contribution].

PMID- 8146379
TI  - [Monostotic Paget's disease of the left mandible. A case report].

PMID- 8146380
TI  - [Acute occlusion of the abdominal aorta. Diagnosis with computed tomography with
      contrast media].

PMID- 8146381
TI  - [Hemangiopericytoma of the duodenum. Report of a case].

PMID- 8146382
TI  - [Colo-uterine fistula. Report of a case].

PMID- 8146383
TI  - [Annular pancreas: assessment with computerized tomography and aqueous contrast
      media].

PMID- 8146384
TI  - [Ultrasonographic aspects of gallbladder varices. 2 case reports].

PMID- 8146385
TI  - [Clinico-ultrasonographic inconsistency in hypertrophic pyloric stenosis].

PMID- 8146386
TI  - HIV disease in Africa.

PMID- 8146387
TI  - [The association between glyoxalase I and paracoccidioidomycosis infection].
AB  - With the purpose to study the genetic susceptibility to paracoccidioidomycosis
      infection we searched for a possible association between glyoxalase I and the
      intradermic paracoccidioidin reaction. The phenotype GLO 1 was significantly more
      frequent among positive reactors.

PMID- 8146388
TI  - Re-evaluation of the basic procedures involved in the storage of measles vaccine
      in public health units of the municipality of Niteroi, State of Rio de Janeiro,
      Brazil.
AB  - Four years after the first visit seventeen public health units were visited again
      and evaluated as to standards of storage recommended by the Brazilian
      Immunization Programme. In 100% of the units, refrigerators and proper inside
      location of vaccines in the refrigerator were adequately or regularly maintained
      and checked, respectively. However, when control of temperature was checked, only
      64.7% presented adequate storage conditions. In 94.1% of the units, health
      workers complained of lack of immediate technical support in emergency
      situations. In 55.2% the titers vaccine samples of were under the minimal
      recommended potency. It is necessary that the factors concerning the cold chain
      be continually evaluated so that the quality of the vaccines that will be used is
      not affected.

PMID- 8146389
TI  - [An evaluation of the effect of a bark extract from the cashew (Anacardium
      occidentale L.) on infection by Leishmania (Viannia) braziliensis].
AB  - This paper presents an evaluation of the therapeutic effect of an hydroalcoholic
      extract of A. occidentale L. bark against Leishmania (Viannia) brasiliensis. The
      extract showed high activity in the in vitro model against the promastigotes of
      this species. However in the in vivo model no curative activity was observed.

PMID- 8146390
TI  - [Mefloquine chemoprophylaxis of malaria in the Brazilian Amazonia].
AB  - In a randomised double-blind study 122 volunteers living in an endemic malarious
      area in Amazonian Rondonia state were divided into 4 groups to study malaria
      suppression. . The first group received 500 mg of mefloquine every month, group
      II 250 mg every two weeks, group III a tablet of Fansidar (500 mg sulphadoxine +
      25mg pyrimethamine) a week and group IV placebo. Acute attacks of malaria
      occurred in one individual in group I, 2 subject in group II, and 6 individuals
      in groups III and IV. Protection with mefloquine was significant compared with
      the placebo group. Both treatment regimens with mefloquine were effective
      suppressants in an area of high prevalence of drug multiresistant Plasmodium
      falciparum transmission.

PMID- 8146391
TI  - [A longitudinal electrocardiogram study of Chagas' disease from the acute phase].
AB  - Several studies have been done to analyse the relationship between the
      characteristics of the electrocardiogram (ECG) and mortality in the several
      stages of the disease, using different methods like multiple case and
      longitudinal studies. We analysed the ECG from the acute stage up to twenty years
      of follow-up (+/- 9 years) in 42 patients with Chagas' disease to determine their
      evolution and it's value like an index for therapeutic evaluation. The 42
      patients (18 female, 24 males) were originally from the north of the State of
      Minas Gerais (Brazil) and the initial stage was mainly in the first two decades
      of age. All bad cardiac involvement and received full specific treatment. We
      utilized the following criteria for the ECG analyses: Modified Minnesota Code for
      Chagas' disease; WHO/ISFC TASK FORCE for inter ventricular conduction
      disturbances and Pieretti criteria for inactive electrical areas. We conclude
      that: a) The electrocardiogram changes tend to get worse with evolution into the
      chronic stage; b) The electrocardiogram is not a good index for therapeutic
      valuation.

PMID- 8146392
TI  - Intestinal helminthiases in Ecuador: the relationship between prevalence,
      genetic, and socioeconomic factors.
AB  - Prevalence of infection with the intestinal helminths, Ascaris lumbricoides,
      Trichuris trichiura, Ancylostoma duodenale and Strongyloides stercoralis was
      examined in 632 residents of communities in Esmeraldas Province of Ecuador. These
      communities were divided into two groups according to area of habitation which
      reflected different socioeconomic circumstances. Attempts were made to correlate
      infection status with race and ABO blood group phenotype. The racial groups
      included blacks, Chachi amerindians, and mixed-race mestizos. Greater prevalences
      of infection were seen in the area of lower socioeconomic status. No racial or
      blood group associations with helminth infection were seen controlling for
      socioeconomic status.

PMID- 8146393
TI  - [Lymphadenopathies in American cutaneous leishmaniasis: comments on 2 cases].
AB  - Two patients, with cervical lymphadenopathies and a presumptive diagnosis of
      lymphoma or scrofula, were submitted to biopsies of the affected lymph nodes.
      Unexpectedly, the histological picture revealed a necrotic-granulomatous reaction
      and the presence of leishmania (amastigotes) in some vacuolated macrophages. The
      patients were from different endemic areas of leishmaniasis in Brazil, and had no
      perceptible cutaneous or mucosal lesions. Later, however, one of them developed
      such lesions, probably as an effect of a treatment for toxoplasmosis. These
      findings support the idea that the agents of the disease, once in the host
      organism, would invade the organs of the phagocytic-mononuclear system, there
      remaining for a long time, maybe for the rest of the host life. Eventually, under
      the action of several factors, that could modify the host resistance, the
      parasites migrate to the skin or the mucosal membranes, causing secondary or
      reactivating lesions.

PMID- 8146394
TI  - [AIDS--an ethical-political focus].

PMID- 8146395
TI  - How dangerous is radon in buildings?--some reflections from Europe.

PMID- 8146396
TI  - Exposure to chlorination by-products from hot water uses.
AB  - Exposures to chlorination by-products (CBP) within public water supplies are
      multiroute in water. Cold water is primarily used for ingestion while a mixture
      of cold water and hot water is used for showering, bathing others, dish washing,
      etc. These latter two activities result in inhalation and dermal exposure.
      Heating water was observed to change the concentration of various CBP. An
      increase in the trihalomethanes (THM) concentrations and a decrease in the
      haloacetonitriles and halopropanones concentration, though an initial rise in the
      concentration of dichloropropanone, were observed. The extent of the increase in
      the THM is dependent on the chlorine residual present. Therefore, estimates of
      total exposure to CBP from public water supplies need to consider any changes in
      their concentration with different water uses. The overall THM exposures
      calculated using the THM concentration in heated water were 50% higher than those
      calculated using the THM concentration present in cold water. The estimated
      lifetime cancer risk associated with exposure to THM in water during the shower
      is therefore underestimated by 50% if the concentration of THM in cold water is
      used in the risk assessment.

PMID- 8146398
TI  - Societal risk perception and media coverage.
AB  - The study compares societal risk ratings by inhabitants of two countries which
      differ markedly in terms of geography, economics, politics, and ethnic
      background, but which are similar as regards media coverage. The two populations
      were represented by a sample of French students and a sample of Burkina Faso
      intellectuals. The overall Burkinabe mean ratings appeared much closer to the
      mean observed in France (and in the United States-roughly 40 out of 100) than the
      means reported for other countries like Norway or Hungary. The correlation
      between Burkinabe and French ratings was very high: .852. The findings argue in
      favor of a practically totally determinant effect of the media in risk
      perception.

PMID- 8146397
TI  - The risk of photochemical reactions.
AB  - In January 1987, an incident occurred at a petrochemical complex in Salavat,
      Russia. The incident resulted in the poisoning of 17 people by the products of
      photochemical smog. This paper describes the incident and discusses the
      possibility of chemical reactions that pose toxic hazardous situations for
      chemical plant personnel. Pollutants present in the atmosphere as a result of
      continuous releases can result in the formation of toxic substances and the
      poisoning of people, even when permissible levels of concentrations are not
      exceeded for the initial pollutants. In addition, this paper addresses the need
      to consider the possibility of secondary chemical reactions in the environment
      while planning chemical plant activity.

PMID- 8146399
TI  - A distributional approach to characterizing low-dose cancer risk.
AB  - Since cancer risk at very low doses cannot be directly measured in humans or
      animals, mathematical extrapolation models and scientific judgment are required.
      This article demonstrates a probabilistic approach to carcinogen risk assessment
      that employs probability trees, subjective probabilities, and standard
      bootstrapping procedures. The probabilistic approach is applied to the
      carcinogenic risk of formaldehyde in environmental and occupational settings.
      Sensitivity analyses illustrate conditional estimates of risk for each path in
      the probability tree. Fundamental mechanistic uncertainties are characterized. A
      strength of the analysis is the explicit treatment of alternative beliefs about
      pharmacokinetics and pharmacodynamics. The resulting probability distributions on
      cancer risk are compared with the point estimates reported by federal agencies.
      Limitations of the approach are discussed as well as future research directions.

PMID- 8146400
TI  - Does protecting for human health protect ecological health?

PMID- 8146401
TI  - High risk or low: how location on a "risk ladder" affects perceived risk.
AB  - Efforts to explain risk magnitude often rely on a "risk ladder" in which exposure
      levels and associated risk estimates are arrayed with low levels at the bottom
      and high ones at the top. Two experiments were conducted to test the hypothesis
      that perceived threat and intended mitigation vary with the location of the
      subject's assigned level on the risk ladder. Subjects were New Jersey homeowners,
      asked to assume a particular level of radon or asbestos contamination in their
      homes, to read a brochure explaining the risk, and then to complete a
      questionnaire. Both studies found that the difference between an assigned level
      one-quarter of the way up the ladder and the same level three-quarters of the way
      up the ladder significantly affected threat perception; the effect on mitigation
      intentions was significant in only one of the studies. Variations in assigned
      risk also affected threat perception and mitigation intentions. Variations in
      test magnitude (e.g., 15 fibers per liter vs. 450 fibers per cubic foot, roughly
      equivalent risks) had no effect, nor did the distinction between radon and
      asbestos affect the dependent variables. These findings suggest that
      communicators can design risk ladders to emphasize particular risk
      characteristics.

PMID- 8146402
TI  - Assessing health risks associated with DDT residues in soils in California: a
      Proposition 65 case study.
AB  - Population growth in California has increased the pressure to convert
      agricultural land to commercial, industrial, or residential uses. In the ensuing
      property transactions, buyers and sellers must address the presence of toxic
      materials in soils such as pesticides, several of which are known to the State of
      California to cause cancer under Proposition 65. While this statute does not
      specifically address soil contaminants, the potential scope of its enforcement is
      sufficiently broad that owners of former agricultural properties may be obliged
      to provide warning of exposure to potential buyers, occupants, or construction
      workers about exposure to residues in soil from pesticide applications. However,
      Proposition 65 provides no guidance on how to assess exposures to chemicals in
      soil. The U.S. EPA Risk Assessment Guidance for Superfund (RAGS) provides a
      method for assessing soil-related exposure pathways that is consistent with the
      intent of Proposition 65. Using this approach, we have calculated the lifetime
      average concentrations of DDT in soil corresponding to the no-significant-risk
      level stipulated under Proposition 65 (1 x 10(-5)) for a hypothetical residential
      exposure scenario. The concentration of DDT in soil corresponding to a no
      significant-risk ranges from 7.9-18.8 mg/kg, depending upon which exposure
      pathways are deemed to be complete for residential land use. It is argued that
      Proposition 65 forces the assessment and possible cleanup of such a situation
      through the threat of creating a health risk perception that could affect the
      market value of a property.

PMID- 8146403
TI  - Perceived risks of radioactive waste transport through Oregon: results of a
      statewide survey.
AB  - Transportation of hazardous materials, and particularly radioactive wastes, on
      public highways has become an important risk management issue. The unfavorability
      of public attitudes regarding hazardous and nuclear wastes signals the potential
      for strong public opposition to programs for transporting these materials. This
      paper presents the results of a survey conducted to assess public reactions to a
      long-term nuclear waste transport program planned to follow a route through a
      portion of rural Oregon. The survey assessed a number of key risk perception
      issues, including perceived health and safety risks of nuclear waste transport,
      relative risks of transport vs. storage at an existing site, trust in state
      officials, and satisfaction with life in communities along the transport route.
      The survey identified a number of attitudes and concerns that need to be
      understood and considered by those in charge of designing and implementing the
      waste-transportation program.

PMID- 8146404
TI  - The benefits of probabilistic exposure assessment: three case studies involving
      contaminated air, water, and soil.
AB  - Probabilistic risk assessments are enjoying increasing popularity as a tool to
      characterize the health hazards associated with exposure to chemicals in the
      environment. Because probabilistic analyses provide much more information to the
      risk manager than standard "point" risk estimates, this approach has generally
      been heralded as one which could significantly improve the conduct of health risk
      assessments. The primary obstacles to replacing point estimates with
      probabilistic techniques include a general lack of familiarity with the approach
      and a lack of regulatory policy and guidance. This paper discusses some of the
      advantages and disadvantages of the point estimate vs. probabilistic approach.
      Three case studies are presented which contrast and compare the results of each.
      The first addresses the risks associated with household exposure to volatile
      chemicals in tapwater. The second evaluates airborne dioxin emissions which can
      enter the food-chain. The third illustrates how to derive health-based cleanup
      levels for dioxin in soil. It is shown that, based on the results of Monte Carlo
      analyses of probability density functions (PDFs), the point estimate approach
      required by most regulatory agencies will nearly always overpredict the risk for
      the 95th percentile person by a factor of up to 5. When the assessment requires
      consideration of 10 or more exposure variables, the point estimate approach will
      often predict risks representative of the 99.9th percentile person rather than
      the 50th or 95th percentile person. This paper recommends a number of data
      distributions for various exposure variables that we believe are now sufficiently
      well understood to be used with confidence in most exposure assessments. A list
      of exposure variables that may require additional research before adequate data
      distributions can be developed are also discussed.

PMID- 8146405
TI  - Can long-term exposure distributions be predicted from short-term measurements?
AB  - A method for estimating long-term distributions of exposure based on repeated
      short-term measurements within the same population is developed. If the short
      term measurements span seasonal variation, and if the distributions are log
      normal or nearly so, then long-term distributions can be estimated from as few as
      two visits to the same population. The method is illustrated using examples drawn
      from EPA's TEAM Study of exposures to volatile organic compounds.

PMID- 8146406
TI  - A structured literature review for risk assessment: EMF and human health risk.
AB  - The volume of publications on any given topic makes it difficult to select an
      appropriate subset of publications for review by an expert panel. This paper
      proposes a method for selecting a subset using a protocol that attempts to order
      publications based upon good research methods. The protocol was followed by
      graduate students with no expert knowledge of the area they were reviewing. They
      reduced 11730 articles on the topic of EMF and Health risk to 68 articles that
      were reviewed by an expert panel. The interrater reliability was 96% and 94% of
      the relevant articles were captured by this process.

PMID- 8146407
TI  - Early and late asthmatic reaction after allergen challenge.

PMID- 8146408
TI  - Respiratory muscle function in patients with asbestos-related pleural disease.
AB  - The effect of asbestos-related pleural disease (ARPD) on the generation of
      maximum respiratory pressure was investigated in 11 male patients with ARPD mean
      age 57 years, range 45-74, and mean duration of asbestos exposure of 9.9 years,
      range 5-16. There were three smokers, seven ex-smokers and one non-smoker.
      Breathlessness ranged from grade 1-3 on the MRC score. The extent of pleural
      disease was calculated using a score based on the ILO score for pleural disease.
      Full respiratory function tests, global respiratory muscle strength and
      diaphragmatic strength were assessed. Respiratory muscle strength, including
      diaphragm strength, was normal. Recoil pressure was high or at the upper limit of
      normal in four patients and correlated with chest radiograph score for pleural
      disease (r = 0.65, P < 0.02). There was no difference in either global
      respiratory muscle or diaphragmatic strength between patients with and without
      involvement of one or both costophrenic angles or between patients with mild or
      severe breathlessness. We conclude that respiratory muscle strength is not
      importantly reduced in ARPD, and it is unlikely that weakness contributes to
      breathlessness in these patients. By contrast reduced chest wall compliance is
      likely to be an important factor in breathlessness in some cases.

PMID- 8146409
TI  - The effect of controlled-release salbutamol on sleep and nocturnal oxygenation in
      patients with asthma and chronic obstructive pulmonary disease.
AB  - Patients with asthma or chronic obstructive pulmonary disease (COPD) may have
      falls in oxygen saturation at night. We have investigated the effect of a long
      acting beta agonist (salbutamol CR) on nocturnal oxygen saturation (SaO2) in
      asthma and COPD. Eleven asthmatic and 14 COPD patients in stable condition were
      randomly allocated to 8 mg salbutamol CR or placebo twice daily in a double
      blind, cross-over study. FEV1 at entry was 71.5% predicted in the asthmatic
      patients and 36% predicted in the COPD group. Each treatment period lasted 7
      days, at the end of which measurements of ventilatory function and detailed sleep
      studies were performed. There was a significant improvement in morning FEV1 in
      the asthmatic patients when on active treatment and a small, but non-significant
      improvement in the COPD group. Sleep architecture and oxygenation were similar on
      placebo and on active treatment in both groups. We conclude that salbutamol CR
      has no significant effect on nocturnal oxygenation or sleep pattern in patients
      with mild asthma or moderately severe COPD.

PMID- 8146410
TI  - Brief upper airway dysfunction.
AB  - We have analysed the clinical manifestations of nine patients with brief upper
      airway dysfunction (BUAD) who attended the thoracic department of a major
      teaching hospital between 1987 and 1991. Episodes of BUAD developed within 1-4
      months of presentation in three patients but were undiagnosed for 2.5-12.5 years
      in six. The mean age at onset was 51 years ranging from 37 to 66 years. The
      episodes occurred at irregular intervals. They lasted approximately 1-5 min, were
      frightening and consisted of an initial phase of obstructive apneoa lasting a few
      seconds to 2 min and a second phase of respiratory distress with inspiratory
      stridor lasting 1-4 min. Daytime episodes occurred in all and at night in five,
      waking three of the patients from sleep. In most instances, throat irritability
      triggered the episodes which were often preceded by cough. Potential causes of
      throat irritability included respiratory tract infection, allergy, oesophageal
      reflux and obstructive sleep apnoea. After treatment of throat irritability BUAD
      has ceased for at least a year in six of the eight with adequate follow-up. In
      conclusion, BUAD has characteristics clinical features which should enable it to
      be recognized more frequently, ensuring successful management.

PMID- 8146411
TI  - Flexible bronchoscopy under 10 kg.
AB  - We report 35 bronchoscopies performed in 27 post-neonatal subjects weighing less
      than 10 kg using an Olympus BC3F20 (3.5 mm diameter) bronchoscope. Twenty-three
      procedures were performed primarily for investigation of airway anatomy and 12
      primarily for broncho-alveolar lavage. Mild oxygen desaturation responsive to
      increased O2 administration was common. Major complications were infrequent with
      two children developing lower respiratory tract infection and one patient
      requiring ventilation overnight. The diagnostic yield was high with 76% of
      studies in children suspected of airway anomalies proving positive. We conclude
      that bronchoscopy in this age group is well tolerated and identifies a
      significant number of abnormalities.

PMID- 8146412
TI  - Heart-lung transplantation in cystic fibrosis: predictions for the next decade in
      England and Wales.
AB  - Heart-lung transplantation has become an established treatment for end stage
      respiratory failure secondary to cystic fibrosis. The success of this form of
      treatment, and the increasing survival of such patients, suggests there will be
      an increased need for transplantation over the next decade. We have used cystic
      fibrosis population predictions and all cause mortality data to estimate the
      number of cardio-pulmonary deaths, due to cystic fibrosis, over the next decade
      and to estimate the number of such patients who are likely to benefit from heart
      lung transplantation. We estimate that there will be between 85 and 127 potential
      transplant recipients with cystic fibrosis each year over the next decade. During
      1990, 1991 and 1992 there were less than 40 transplants each year in such
      patients. These data emphasize the need to expand transplantation services and to
      maintain the availability of donor organs.

PMID- 8146413
TI  - A comparison study of IFN-gamma, ADA, and CA125 as the diagnostic parameters in
      tuberculous pleuritis.
AB  - Adenosine deaminase in pleural fluid (pADA), CA125 in serum (sCA125), and IFN
      gamma in pleural fluid (pIFN-gamma) were measured in patients with pleurisy of
      various causes to evaluate their diagnostic utility in tuberculous pleuritis
      (TBP). We studied 39 pleural fluid samples, including 11 TBP and 28 non-TBP. With
      both pADA and sCA125, although the median values were much higher in TBP than in
      non-TBP groups, there was considerable overlap between the two groups. The
      sensitivity, specificity, and diagnostic efficiency were 81.8%, 89.3%, and 87.2%,
      respectively, when pADA values of more than 45 U ml-1 were considered, and they
      were 100%, 75.0%, and 84.2%, respectively, when sCA125 values of more than 35 U
      ml-1 were considered. In contrast, pIFN-gamma values were significantly higher in
      TBP patients (5.8 +/- 3.0 IU ml-1; mean +/- S.D.) than those in non-TBP patients
      (< 0.3 IU ml-1), leading to both a sensitivity and a specificity of 100%.

PMID- 8146414
TI  - Nebulized colistin causes chest tightness in adults with cystic fibrosis.

PMID- 8146415
TI  - Capillary haemangiomatosis: a rare cause of pulmonary hypertension.

PMID- 8146416
TI  - Preoperative physical therapy in the prevention of postoperative lung
      complications.

PMID- 8146417
TI  - Mouth blistering and ulceration associated with inhaled steroids.

PMID- 8146418
TI  - Is increased dietary salt intake a cause of increased airway responsiveness or a
      marker of an unhealthy life style?

PMID- 8146419
TI  - Drug interactions with anti-asthma medication.

PMID- 8146420
TI  - The assessment of nasal mucociliary clearance and the effect of drugs.

PMID- 8146421
TI  - GnRH neurons and other cellular and molecular mechanisms for simple mammalian
      reproductive behaviors.

PMID- 8146422
TI  - A transgenic model for studying islet development.
AB  - The regeneration of islet cells in a transgenic mouse strain harboring the
      interferon-gamma gene (IFN-gamma) linked to the insulin promoter DNA fragment
      (ins-IFN-gamma) is described. The regeneration follows the loss of islets by an
      immune response provoked by IFN-gamma and manifests in the proliferation of duct
      cells, the presence of progenitor cells, and the formation of buds and isletlike
      structure. All three types (A, B, and D) of four endocrine cells identified by
      immunolabeling are present. The progenitor cells express neuronal enzymes,
      tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD), as revealed by
      specific antibodies. The results indicate that the islet regeneration closely
      resembles the embryonic islet differentiation and serves as a model for studying
      islet development. The expression of neuronal enzymes by islet progenitor cells
      signifies yet unknown relationships to the nervous tissue. GAD, recognized as an
      autoantigen in insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome,
      may provide a clue to the mechanism of autoimmune disease.

PMID- 8146423
TI  - Steroid receptors and other transcription factors in ecdysone response.

PMID- 8146424
TI  - Protein phosphatases.

PMID- 8146425
TI  - Prenylation and G protein signaling.

PMID- 8146426
TI  - The androgen receptor: an overview.

PMID- 8146428
TI  - Regulation of the chicken very low density apolipoprotein II gene: interaction of
      estrogen and insulin.

PMID- 8146427
TI  - The molecular genetics of steroid 5 alpha-reductases.

PMID- 8146429
TI  - A novel upstream activator in the mitogen-activated protein kinase signal
      transduction pathway.

PMID- 8146430
TI  - A novel yeast expression system to study androgen action.

PMID- 8146431
TI  - A spermatid factor inhibits cAMP and calcium signaling in Sertoli but not Leydig
      cells.

PMID- 8146432
TI  - Circadian variations of gastrointestinal peptides and cell proliferation in rats:
      effects of adrenalectomy.
AB  - The hypothalamo-pituitary-adrenal axis appears to play an important role in
      regulating the circadian fluctuations of brain-gut peptides, as well as the cell
      cycle of the gastrointestinal mucosa. Since dexamethasone treatment tended to
      restore circadian fluctuations lost to adren-x, the influence of adrenal
      glucocorticoids in the coordination of the rhythms of regulatory peptides and
      cell cycle kinetics appears to be substantial.

PMID- 8146433
TI  - Molecular genetic prenatal diagnosis of congenital adrenal hyperplasia due to 21
      hydroxylase deficiency by allele-specific hybridization.
AB  - The feasibility and accuracy of gene-specific molecular genetic diagnosis for
      congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency were
      studied in a group of 24 pregnancies at 25% risk of carrying an affected fetus.
      Chorionic villus sampling was performed in the majority of cases. Southern blot
      analysis was carried out to identify deletions or other gross rearrangements. In
      parallel, the polymerase chain reaction (PCR) was performed, followed by allele
      specific oligonucleotide hybridization (ASO) for a panel of nine known mutations.
      Mutations were identified in 95% of the chromosomes examined. The molecular
      diagnosis was accurate in 23 of 24 infants. The most common mutation identified
      was an A-to-G transition in the second intron (52% of affected chromosomes), the
      result of an apparent gene conversion. One fetus carried homozygous deletion of
      CYP21, which accounted for 13% of all affected chromosomes. Other mutations
      identified included an 8-bp deletion in the third exon (22%); Ile172 to Asn, a
      nonconservative substitution, in the fourth exon (9%); and Gln318 to term, a
      nonsense mutation, in the eight exon (4%). No mutation was detected in CYP21 in
      5% of obligate-affected chromosomes examined by these methods.

PMID- 8146434
TI  - 7 alpha-Methyl-19-nortestosterone: an ideal androgen for replacement therapy.
AB  - MENT is a synthetic androgen which cannot be 5 alpha-reduced. Therefore, relative
      to T, its stimulatory action on the prostate is lower than that on the muscle and
      pituitary. Like T, MENT undergoes enzymatic aromatization to an estrogen. We
      conclude that the use of MENT instead of T for androgen replacement therapy could
      have health-promoting effects by reducing the occurrence of prostate disease.

PMID- 8146435
TI  - Alpha-1 and beta-1 thyroid hormone receptors on human granulosa cells.

PMID- 8146436
TI  - Dopaminergic stimulation of estrogen receptor binding in vivo: a reexamination.

PMID- 8146437
TI  - Circadian rhythms.
AB  - Changes in behavior which occur on a daily or circadian basis represent one of
      the most ubiquitous strategies by which most living organisms have adapted to
      their environment. Underlying the daily changes in behavior are a multitude of
      endocrine and metabolic rhythms which provide adaptively significant temporal
      organization within the organism. In mammals there appears to be a central
      circadian clock in the SCN which is responsible for generating and coordinating
      the entire 24-hour temporal organization of the animal. The circadian clock
      regulates the timing, duration, and characteristics of sleep, and together the
      circadian clock and sleep interact to control the timing of endocrine secretions.
      While the impact of disturbed endocrine circadian rhythms for the survival of the
      species has received very little attention, the almost universal presence of
      circadian rhythmicity within the endocrine system argues in support of the
      hypothesis that a disruption of the normal circadian organization within the
      endocrine system can have serious consequences for the health and well-being of
      the organism. It is particularly noteworthy that in advanced age, various
      alterations in circadian endocrine rhythms have been observed and these
      alterations may impair the ability of the animal to adapt normally to the
      environment. Relatively speaking, the study of circadian rhythms is a new field
      of biology, and as a result, much remains to be discovered about the
      physiological mechanisms that underlie rhythmicity, as well as the functional
      significance of 24-hour temporal organization for the survival of the species.

PMID- 8146438
TI  - Regulation of pancreatic beta-cell mass in vivo.

PMID- 8146439
TI  - Effects of dietary vitamin E and selenium on in vitro cellular immune responses
      in cattle.
AB  - Four groups of calves depleted of alpha-tocopherol and selenium (Se) were
      supplemented with alpha-tocopherol or Se or alpha-tocopherol and Se or received
      no supplement. In vitro lymphocyte proliferative responses were measured in fetal
      calf serum (FCS), in autologous serum and in pooled sera from each group. In FCS,
      the responses to pokeweed mitogen were significantly enhanced for calves
      supplemented with alpha-tocopherol. In autologous serum, the mean responses to
      keyhole limpet haemocyanin (KLH) were greatest for calves supplemented with Se
      alone. In pooled sera from each group, lymphocytes from calves supplemented with
      Se alone showed enhanced responses to KLH in the presence of serum from calves
      supplemented with alpha-tocopherol. The calves depleted of alpha-tocopherol had
      increased circulating percentages of BoCD2 lymphocytes, apparently due to changes
      in the BoCD4 subpopulation. The percentages of B cells were greatest in calves
      supplemented with alpha-tocopherol and Se. The results indicate that alpha
      tocopherol and Se have interactive effects on lymphocyte responses to antigen and
      suggest that micronutrient status is important when interpreting the results of
      in vitro assays of lymphocyte function.

PMID- 8146440
TI  - Isolation of Mycoplasma hyorhinis and Mycoplasma arginini from the ears of pigs
      with otitis media.
AB  - Mycoplasmas were isolated from the middle ears and nasal cavities of clinically
      ill, young pigs that were slaughtered due to an unfavourable prognosis. The
      isolation rates of Mycoplasma hyorhinis were 27 of 43 (62.8 per cent) from the
      auditory tube, 22 of 43 (51.2 per cent) from the tympanic cavity, and 15 of 25
      (60.0 per cent) from the nasal cavity. M arginini was also recovered at rates of
      11 of 43 (25.6 per cent) from the auditory tube, 7 of 43 (16.3 per cent) from the
      tympanic cavity, and 9 of 25 (36.0 per cent) from the nasal cavity. Dual
      infections with M hyorhinis and M arginini occurred in these sites in some cases.
      M hyorhinis was isolated from 16 (80.0 per cent) of 20 pigs with otitis media
      diagnosed histologically, and from two (25.0 per cent) of eight pigs without this
      condition. The isolation rate was significantly different (P < 0.05) between the
      groups, suggesting either that the organism triggers development of the disease
      of the ear or that the agent(s) or factors responsible for otitis media in the
      pigs created favourable conditions at this site for colonisation by M hyorhinis.

PMID- 8146441
TI  - Detection of enzootic pneumonia in pig herds using an enzyme-linked immunosorbent
      assay in sow colostrum.
AB  - A total of 6256 colostrum samples from 185 Finnish pig health scheme herds were
      screened for Mycoplasma hyopneumoniae antibodies, using a commercial ELISA kit,
      between November 1989 and April 1991. Most (162) of the herds were negative. In
      six herds, in which positive colostrum samples were found, the presence of
      enzootic pneumonia was confirmed by clinical and pathological findings. One herd
      had several seropositive sows but no clinical disease and in 16 herds occasional
      positive colostrum samples were found. Antibodies appeared in the colostrum four
      days to six months before the signs of the clinical disease; the number of
      seropositive sows was low (average 10.6 per cent). The specificity of the ELISA
      was estimated to be as high as 99.4 per cent in this study. Colostrum appeared to
      be a suitable sample for ELISAS.

PMID- 8146442
TI  - Lack of effect of quinidine on divalent mineral absorption from the reticulorumen
      of sheep.
AB  - The effects of quinidine on divalent mineral absorption were studied using normal
      and high potassium intraruminal buffers with the in vivo isolated washed rumen
      technique. A concentration of 1 mmol litre-1 quinidine in the intraruminal buffer
      decreased the absorption rates of Na+ and C1- from the rumen but had no
      significant effect on the absorption rates of Mg2+, Ca2+ and K+. Prolonged oral
      administration of quinidine had no significant effect on the absorption of any of
      these ions from either a normal or a high potassium ruminal solution.

PMID- 8146443
TI  - Homogeneity of the major outer membrane protein gene of feline Chlamydia
      psittaci.
AB  - Thirteen feline Chlamydia psittaci strains isolated in various countries over a
      50-year period were examined by restriction mapping of the major outer membrane
      protein (MOMP) gene obtained after DNA amplification by the polymerase chain
      reaction and compared with avian, ovine and guinea pig inclusion conjunctivitis
      (GPIC) C psittaci strains. All the feline isolates produced a unique AluI pattern
      distinct from the other C psittaci strains and were characterised by a typical
      fragment doublet of 185/180 base pairs. Such a homogeneity argues for their
      genetic relatedness and suggests their clonal origin. These data demonstrate the
      usefulness of MOMP-gene restriction mapping in C psittaci typing.

PMID- 8146444
TI  - Effects of repeated challenges with exogenous oestradiol benzoate and
      progesterone on reproduction in prepubertal Hubei white and Meishan cross gilts.
AB  - Two experiments were carried out to investigate the effects of repeated
      challenges of oestradiol benzoate and progesterone on reproduction in prepubertal
      gilts. In experiment 1, 21 Large White cross (Meishan cross Landrace) prepubertal
      gilts were allocated to one of three treatments. Treatment A gilts were given
      oestradiol benzoate injections (15 micrograms kg-1 bodyweight) at 140 and 160
      days old and daily injections of progesterone (20 mg day-1 per gilt) for four
      days, from day 12 after each oestradiol benzoate challenge. Treatment B gilts
      were given the same oestradiol benzoate and progesterone challenges but from 160
      days onwards. Treatment C gilts were the controls and were given only oil
      injections. All the gilts were mated at their first oestrous period. In
      experiment 2, 45 prepubertal Hubei White gilts were allocated to the same
      treatments as used in experiment 1. The administration of oestradiol benzoate
      induced oestrus (52 of 64) and ovulation (51 of 64) in a high proportion of the
      gilts in both experiments. The proportions of gilts which had regular oestrous
      cycles (within 10 days after progesterone withdrawal) were 0.82 (18 of 22) and
      0.16 (3 of 19) in treatments A and B, respectively (P < 0.001).

PMID- 8146445
TI  - Analysis of schizont antigen of Leucocytozoon caulleryi by SDS-PAGE and western
      blot.
AB  - To investigate the molecular weight of the schizont antigen of Leucocytozoon
      caulleryi, the schizont antigen was analysed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) and western blot. Thirty to 35
      protein bands were detected by SDS-PAGE under reduced condition and ranged from
      25 to 300 kDa. Most of them reacted with the sera of infected chickens by Western
      blot. The bands corresponding to polypeptides of 44, 58, 67 and 180 kDa reacted
      strongly, however, the bands of 30, 50 and 78 kDa did not react.

PMID- 8146446
TI  - Urinary concentration of corticoids in normal horses and horses with
      hyperadrenocorticism.
AB  - The urinary corticoid:creatinine (c:c) ratio was determined in eight horses with
      hyperadrenocorticism (HAC). The mean (+/- SD) urinary c:c ratio of the eight
      horses with HAC (29 +/- 14 x 10(-6)) was significantly (P < 0.05) greater than
      the ratio in seven control horses (11 +/- 4.3 x 10(-6)). The urinary
      concentration of corticoids in control horses (201 +/- 60.4 nmol litre-1) was
      significantly (P < 0.05) lower than in horses with HAC (664 +/- 291 nmol litre
      1). The urinary creatinine concentrations did not differ significantly (P > 0.05)
      between both groups. As both false negative and false positive cases were found,
      it is concluded that a measurement of the urinary c:c ratio in the horse should
      not be used as the sole test to confirm equine HAC.

PMID- 8146447
TI  - Effect of non-adrenal illness, anaesthesia and surgery on plasma cortisol
      concentrations in dogs.
AB  - Basal plasma cortisol concentrations in 25 dogs with non-adrenal illness were two
      to three times higher than in 25 normal dogs (158 +/- 25 nmol litre-1 compared
      with 65 +/- 22; mean +/- SD). In addition, plasma cortisol concentrations were
      measured in 12 animals undergoing major abdominal, thoracic or orthopaedic
      surgery and compared to a group of six anaesthetised dogs. Anaesthesia alone
      failed to significantly alter plasma cortisol levels, however, all forms of
      surgery produced a significant increase in plasma cortisol concentration which
      returned to normal 24 hours after completion of surgery.

PMID- 8146448
TI  - An immunopathological study of deep pyoderma in the dog.
AB  - The numbers of T lymphocytes (expressing the CD3 marker) and B lymphocytes/plasma
      cells (expressing IgG, IgM or IgA) in normal canine skin and infiltrating the
      lesions of deep pyoderma in seven German shepherd dogs and four dogs of other
      breeds are compared. All dogs with deep pyoderma had similar numbers of IgG, IgM
      and IgA bearing B lymphocytes/plasma cells but there was a marked paucity of T
      lymphocytes within the affected skin of German shepherd dogs when compared with
      that of dogs from other breeds. This suggests a role for T cell dysfunction in
      the pathogenesis of deep pyoderma in the German shepherd dog.

PMID- 8146449
TI  - Comparison of results of haematological and clinical chemical analyses of blood
      samples obtained from the cephalic and external jugular veins in dogs.
AB  - The study was performed to investigate the difference in the concentration of
      several haematological and clinical chemical blood components in blood obtained
      from the cephalic and external jugular veins in 23 dogs. A total of 17 laboratory
      tests were analysed and, except for two clinical chemical blood components, there
      was no decisive difference in the test results obtained in blood samples
      collected from the cephalic and external jugular vein in dogs. For creatinine and
      potassium, however, there was a significant difference in the test results
      between the two veins, the highest results in general being measured in jugular
      venous blood. These findings indicate that it may be advisable to establish
      standardised procedures when collecting blood samples and make adjustments for
      the difference in test results when interpreting them.

PMID- 8146450
TI  - Creatine kinase in dog plasma: preanalytical factors of variation, reference
      values and diagnostic significance.
AB  - In the dog, plasma creatine kinase (CK) activity was stable up to one week at +4
      degrees C and one month at -20 degrees C. Activity was higher in serum than in
      plasma due to interference by CK from the platelets. The reference values were
      determined in 232 dogs using the IFCC recommended method. There was a significant
      decrease in activity with age but no effect of sex. In adults, plasma CK
      exhibited a log-normal distribution ranging from 20 to 104 U per litre. In 510
      dogs with various diseases, the overall sensitivity and specificity of CK
      determination were 40 per cent and 98 per cent, respectively. The numerous false
      negatives could result from the relatively short half-life of the enzyme, while
      the false positives could be due to secondary muscle damage.

PMID- 8146451
TI  - Toxicity of aflatoxin B1 in broiler chicks and its reduction by activated
      charcoal.
AB  - A study was conducted on 60 broiler chicks of the effect of activated charcoal
      (200 ppm) on the toxicity of 0.5 ppm aflatoxin B1 (AFB1) in feed fed from day 1
      to day 42. Activated charcoal was found to be moderately effective in reducing
      the harmful effects of AFB1 as assessed by growth response and various
      biochemical parameters. The feeding of activated charcoal along with AFB1 reduced
      the inhibitory effect of AFB1 on bodyweights and feed intake. There was also a
      significant improvement in the serum aspartate aminotransferase, alkaline
      phosphatase, total proteins, calcium and phosphorus levels. However, no
      significant improvement was observed in cholesterol levels.

PMID- 8146452
TI  - Antibody-containing cells in the abomasal mucosa of sheep with genetic resistance
      to Haemonchus contortus.
AB  - The frequency distribution of parasite-specific antibody-containing cells (ACC)
      and total immunoglobulin-containing cells (ICC) in the abomasal mucosa was
      examined in genetically resistant and random-bred sheep, following infection with
      Haemonchus contortus, to determine whether the two genotypes differed in the
      development of a local immune response. Immunofluorescence staining was used to
      detect ACC and ICC of IgA, IgG1, IgG2 and IgM classes. No ACC were found in the
      abomasum of any of the sheep before infection. ACC were first detected in the
      abomasal mucosa of both the resistant and susceptible sheep seven days after
      infection, reached a peak level on day 21 and then declined. At all observation
      times, the majority of ACC in both genotypes were of the IgA isotype, followed by
      IgG1 and IgM. The IgG2-ACC response was negligible compared with the IgA and IgG1
      response. The comparison of genotypes showed that the resistant sheep had
      significantly more IgA-ACC on days 14, 21, 28 and 35, and significantly more IgG1
      ACC than random-bred sheep on days 14, 21 and 28. The numbers of IgG2- and IgM
      ACC did not differ between the genotypes. The abomasal mucosa of the resistant
      sheep was also found to have significantly more ICC than the mucosa of random
      bred sheep; IgA-ICC predominated at all the observation times followed by IgG1
      and IgM. These results suggest that IgA and IgG1 antibodies, produced locally in
      response to infection, may play a role in mediating genetic resistance to
      haemonchosis in sheep.

PMID- 8146453
TI  - Oral bioavailability of sulphadiazine and trimethoprim in fed and fasted pigs.
AB  - The disposition of sulphadiazine (SDZ) and trimethoprim (TMP) was measured after
      intravenous and oral administration. Six healthy pigs weighing 17 to 34 kg
      received 20 mg kg-1 SDZ plus 4 mg kg-1 TMP intravenously, and 40 mg kg-1 SDZ plus
      8 mg kg-1 TMP orally in both a fed and a fasted condition in a three-way cross
      over design. After intravenous administration SDZ and TMP were present in plasma
      for 30 and 12 hours, respectively. The volume of distribution was 0.5 litre kg-1
      bodyweight for SDZ and 1.8 litre kg-1 bodyweight for TMP. The oral
      bioavailabilities for SDZ and TMP in the fed pigs were 85 per cent and 92 per
      cent, and in the fasted pigs 89 per cent and 90 per cent, respectively. Although
      the presence of food did not affect the almost complete absorption of both drugs,
      it did prolong the absorption phase. Mean absorption time was nearly twice as
      long in the fed as in the fasted pig. Based on bioavailability and the resulting
      plasma concentrations it is concluded that the oral administration of SDZ and TMP
      was efficient in both the fed and fasted pigs.

PMID- 8146454
TI  - Hypertrophic chondrocyte volume and growth rates in avian growth plates.
AB  - In growing mammals there is a positive linear relationship between the mean
      hypertrophic chondrocyte volume and the rate of bone elongation. This suggests
      that the control of chondrocytic volume in the growth plate, is a major
      determinant in controlling bone elongation in mammals. In the present study the
      existence of such a relationship was tested for in birds. A scheme of
      fluorochrome labelling was devised to enable direct measurement of bone
      elongation per unit time. Four weight-bearing growth plates from two-week-old
      mallard ducklings and the corresponding four growth plates from two-week-old
      leghorn chicks were studied. Growth plate cartilage was fixed in the presence of
      ruthenium hexamine trichloride and embedded in Epon araldite. Estimates of mean
      cell volume, v(chondr), and mean cubic intercept (l3) were calculated by applying
      the stereological relationship: v(chondr) = (pi/3) x (l3). Regression analysis
      revealed a positive linear relationship between the two parameters, rate of bone
      elongation and mean hypertrophic cell volume in both species (squared correlation
      statistics: 65 per cent for mallards, 54 per cent for leghorns). There was a wide
      range in rates of bone elongation among growth plates studied (318 to 1418
      microns 24 h-1 for mallards, 77 to 445 microns 24 h-1 for leghorns) and compared
      to mammals (such as rabbits, rats, swine and dogs), a small range in mean cell
      volume (2709 to 4786 micron3 for mallards, 3663 to 5719 micron3 for
      leghorns).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146455
TI  - Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis.
AB  - The efficacy of ketoprofen in the treatment of acute clinical mastitis was
      evaluated in a clinical trial comprising a non-blind controlled study and a
      blind, placebo-controlled study. All the cows were treated with 20 g
      sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the
      dosage was given once daily thereafter. In addition, the ketoprofen treatment
      groups received 2 g ketoprofen intramuscularly once daily for the duration of the
      antimicrobial therapy. Recovery rates for the non-blind contemporary controls and
      the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively. In
      the non-blind controlled ketoprofen and the placebo-controlled ketoprofen
      treatment groups, recovery rates were 94.7 per cent and 92.3 per cent,
      respectively. The odds ratio (OR) of recovery was significantly (P < or = 0.01)
      high in the placebo-controlled study (OR = 6.75, confidence interval [CI] = 1.45
      to 31.4), and high but not significant in the non-blind controlled study (OR =
      2.64, CI = 0.53 to 13.10). It was concluded that ketoprofen significantly
      improved recovery in clinical mastitis in dairy cows.

PMID- 8146456
TI  - The role of GABA receptors in the control of the omasal myoelectrical activity in
      sheep.
AB  - Gamma-aminobutyric acid (GABA) receptor-mediated modification of omasal spiking
      activity (SA) was studied in six conscious ewes at rest, chronically fitted with
      electrodes implanted in the reticular and omasal walls and a cannula placed in
      the left cerebral lateral ventricle. Intracerebroventricular (0.1 microgram kg-1)
      but not intravenous (25 micrograms kg-1) administration of muscimol increased
      both the duration of omasal SA and the frequency of groups of spiking bursts
      (GSB) from the reticulum and oral omasum; the frequency of GSB from the aboral
      omasum decreased. These responses were antagonised by intracerebroventricular
      pretreatment with bicuculline (0.5 microgram kg-1). Both intravenous (500
      micrograms kg-1) and intracerebroventricular (1 microgram kg-1) administration of
      baclofen inhibited reticular SA; in both the oral and aboral omasum, while the
      duration of SA increased, the frequency of GSB decreased. Reticuloomasal
      responses to intravenous or intracerebroventricular baclofen were greatly
      antagonised or abolished, respectively, by a previous intracerebroventricular
      injection of phaclofen (80 micrograms kg-1). The main conclusion which could be
      drawn from these results is that exclusively central GABAA and mainly central
      GABAB receptors mediate a prolongation of omasal body motility in sheep.

PMID- 8146457
TI  - Measurement of right ventricular ejection fraction and volume by the
      thermodilution technique in the unsedated calf.
AB  - This study was designed to test the applicability and the reproducibility of the
      thermodilution method in the measurement of right ventricular ejection fraction
      (EF), end-diastolic volume (EDV) and end-systolic volume (ESV) in unsedated
      cattle. In the 16 healthy calves studied, it was possible, using a fast response
      thermodilution catheter, to obtain characteristic exponential steplike washout
      curves, allowing the calculation of right ventricular EF, EDV and ESV. Five to 10
      successive thermodilution curves were recorded within a few minutes and two to
      five similar sets of measurements were performed throughout the same day to test
      the reproducibility of the technique. The same protocol was repeated the
      following day. Right ventricular EF, EDV and ESV were reproducible successively,
      throughout a given day and on following days. The mean intraset, intraday and
      interdays coefficients of variation ranged from a mean of 4.0 (SD 4.1) per cent
      to a mean of 18.2 (SD 7.9) per cent. Values of right ventricular volumes and EF
      agreed with those previously reported in various animal species. Thermodilution
      was, therefore, shown to be a useful method for measuring with a satisfactory
      reproducibility, right ventricular EF, EDV and ESV in the unsedated healthy calf.

PMID- 8146458
TI  - Effect of different methods of castration on behaviour and plasma cortisol in
      calves of three ages.
AB  - Calves of six, 21 and 42 days were either handled (controls) or castrated by
      Burdizzo, by surgical or by rubber ring techniques and their behaviour and plasma
      cortisol monitored for three hours after treatment. The rubber ring caused
      significant increases in active behaviour and abnormal postures for two hours
      compared with handled or castrated by Burdizzo and surgical techniques, and
      surgical techniques resulted in a significant increase in abnormal standing,
      particularly in the first 30 minutes. Abnormal behaviour and posture were
      recorded less frequently in six-day-old calves. The mean cortisol peaks for six-,
      21- and 42-day-old calves were, respectively, 36, 31 and 23 nmol litre-1 in the
      handled groups; 60, 43 and 48 nmol litre-1 in the rubber ring groups; 77, 50 and
      62 nmol litre-1 in the Burdizzo groups; and 106, 63 and 107 nmol litre-1 in the
      surgical groups. The greatest cortisol response occurred in 42-day-old surgically
      treated calves and the shortest response after Burdizzo castration. These
      responses suggest that irrespective of age, all methods of castration studied
      caused acute pain. Burdizzo castration appeared to produce the least pain,
      particularly in younger calves.

PMID- 8146459
TI  - Changes in plasma lipoprotein during the oestrous cycle of the bitch.
AB  - Five bitches were kept under controlled conditions of diet and exercise for up to
      four months. They were monitored at regular time intervals for fasting plasma
      concentrations of cholesterol, triacylglycerols and apolipoproteins AI and B.
      Lipoprotein cholesterol and triacylglycerol concentrations were also determined
      in the fasting plasma. Vaginal cytology and plasma progesterone were monitored at
      weekly intervals to determine the oestrous state of the bitches. Lipoprotein and
      apolipoprotein concentrations remained steady during anoestrus but large
      increases and wide fluctuations were shown in the concentrations of both
      cholesterol and triacylglycerols during metoestrus. Metabolic studies involving
      the measurement of lipids in canine blood must take into account the stage of
      oestrus of any bitches involved.

PMID- 8146460
TI  - Influence of vaccine medium and vaccination schedules on the induction of active
      immunity against Aujeszky's disease in maternally immune pigs.
AB  - Active immunity against Aujeszky's disease virus (ADV) was compared at the end of
      the fattening period in pigs which had been vaccinated with the attenuated Bartha
      strain according to different schedules in the presence of different levels of
      maternal immunity. The percentage of seropositive pigs at the end of the
      fattening period varied from 21 to 94 per cent. The percentage was significantly
      higher when the vaccination schedules were applied to pigs from mothers
      vaccinated with an attenuated strain compared to pigs from mothers vaccinated
      with a subunit vaccine or from infected-immune mothers. Additionally, this
      percentage was two to three times lower when pigs were vaccinated once at 10
      weeks old compared to pigs either revaccinated at 14 weeks or vaccinated once at
      14 weeks old. When the virus strain used for vaccination had been suspended
      either in saline or in an oil-in-water emulsion, significant differences were not
      found in the serological response after vaccination and in the reduction of virus
      excretion upon subsequent challenge. In challenge experiments, a significantly
      longer duration of virus excretion was observed in vaccinated pigs which had not
      seroconverted than in vaccinated but seropositive pigs. The vaccination schedules
      for sows and fattening pigs in view of the eradication of ADV are discussed.

PMID- 8146461
TI  - Suppression of prostaglandin F2 alpha and oxytocin release after inhibition of
      testosterone synthesis in the goat.
AB  - Increased peripheral plasma concentrations of testosterone were detected in goats
      on days 13 and 14 of the oestrous cycle (oestrus = day 0), at the onset of
      luteolysis. Subcutaneous administration of spironolactone (10 mg kg-1 day-1) on
      days 10 to 19 inhibited the increases in testosterone, delayed luteolysis and
      suppressed plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha
      and oxytocin. These results suggest that testosterone of follicular or luteal
      origin, possibly via aromatisation to oestrogens, is needed to expedite
      luteolysis and induce oestrus in the goat.

PMID- 8146462
TI  - Structures and strategies for general practice research in the United Kingdom.

PMID- 8146463
TI  - Strategies and structures for research in general practice in Finland.

PMID- 8146464
TI  - Research in general practice: Dutch experiences.

PMID- 8146465
TI  - Research in your own practice--advantages and difficulties.

PMID- 8146466
TI  - Different methods of single practice research.

PMID- 8146467
TI  - Single practice research--longterm research.

PMID- 8146468
TI  - Forty years family-based morbidity data in general practice.

PMID- 8146469
TI  - Morbidity registration and the fourth general practice morbidity survey in
      England and Wales.
AB  - The fourth morbidity survey in England and Wales is based on a population of
      473,000 persons registered in 60 practices and cared for by 241 general
      practitioners. This presentation traces the evolution of morbidity surveys in
      England and Wales. That evolution has taken place against a background of
      advancing computer technology and the drift towards a paperless record. It is
      motivated by an increasing recognition of the need for data from primary health
      care an a realisation that a structured record is capable of servicing
      information needs without intermediary data sheets and coding procedures. The
      primary objectives of the study include assessment of disease prevalence by
      region, age-sex and social group; and to study trends over time. Morbidity and
      social data are collected in the practices and all relevant information stored on
      practice computers. At the end of the recording year, the computerised record for
      each patient is copied on to disks in an anonymized but uniquely identified form
      and transferred to the national Office of Population Censuses & Surveys for
      analysis. During the year, weekly extracts are taken of new episodes of illness
      in age and sex groupings which provide the basis of the Weekly Returns Service of
      the Royal College of General Practitioners.

PMID- 8146470
TI  - National and international research in the future in general practice.
AB  - Research suitable for either national or international collaborative activity.
      Structure, strategies, methods and difficulties with collaborative research in
      primary care/general practice based on experiences from EEC/COMAC Health Services
      Research in comparison with activities and possibilities within individual
      countries. The computerized medical record and future patient cards especially
      for epidemiological research in primary care. The advantages and use of sentinel
      data collecting centres in international collaborative research.

PMID- 8146471
TI  - Longitudinal research in general practice. The importance of including both
      patients' and physicians' perspectives on medical events.

PMID- 8146472
TI  - The Danish Study Diabetes Care in General Practice. Management of main
      methodological and practical problems in a long-term multipractice intervention
      study.

PMID- 8146473
TI  - Longitudinal studies of patients with chronic illness problems of linking process
      and outcome.

PMID- 8146474
TI  - Review of approaches to define, describe and analyze the contents of
      consultations.

PMID- 8146475
TI  - The issue of validity regarding the contents of consultations.

PMID- 8146476
TI  - Patients' assessments of the outcomes of primary care consultations.

PMID- 8146477
TI  - Undergraduate courses in family medicine in the UK, Ireland, The Netherlands and
      the Nordic countries.

PMID- 8146478
TI  - Implementation of consultation process research in general practice training.

PMID- 8146479
TI  - Structures and strategies for general practice research in Denmark.

PMID- 8146480
TI  - Differential diagnosis of progressive spastic paraparesis.

PMID- 8146481
TI  - Progressive spinal multiple sclerosis.

PMID- 8146482
TI  - Hereditary spastic paraplegias.

PMID- 8146483
TI  - Spinal cord and foramen magnum tumors.

PMID- 8146484
TI  - Cervical spondylotic myelopathy.

PMID- 8146485
TI  - Spinal vascular malformations.

PMID- 8146486
TI  - Parkinsonian syndromes.

PMID- 8146487
TI  - Inherited motor neuron diseases: recent progress.

PMID- 8146488
TI  - Motor neuron diseases resulting from hexosaminidase deficiency.

PMID- 8146489
TI  - A life-enhancing condition: the Honourable Mr. Justice Sam N. Filer.

PMID- 8146490
TI  - Clinical approach to infertility in the bitch.

PMID- 8146491
TI  - Management of parturition and problems of the periparturient period of dogs and
      cats.

PMID- 8146492
TI  - Clinical management of bitches with vaginal discharge during pregnancy.

PMID- 8146493
TI  - Basics for a complete reproductive examination of the male dog.

PMID- 8146494
TI  - Diagnosis, treatment, and management of poor fertility in the stud dog.

PMID- 8146495
TI  - Pharmaceuticals used in canine reproduction.

PMID- 8146496
TI  - Diagnostic imaging in companion animal theriogenology.
AB  - Clinical assessment of reproductive problems in companion animals is greatly
      enhanced by the availability of various imaging modalities. Specifically, survey
      radiography, contrast radiography, real-time ultrasonography, and ultrasound
      guided biopsy and/or aspiration cytology, alone or in various combinations, offer
      sophisticated methods of extension of the physical examination of the
      reproductive systems of dogs and cats. In particular, real-time ultrasonography
      offers invaluable assistance. It is nonionizing, largely noninvasive, rapid, and
      capable of providing certain dynamic information that is not conveniently
      available in any other way. Judging from its rapid growth in recent years, it has
      apparently become an integral part of the complete reproductive assessment of
      domestic animals. This is not to slight the importance of some of the contrast
      radiographic procedures that have been developed and refined. Some of them, such
      as maximum distention retrograde urothrocystography, provide unique information
      not available with presently routinely used ultrasound techniques. Other imaging
      modalities, such as magnetic resonance imaging, have heretofore provided limited
      benefit to theriogenology; that will probably change in years to come.

PMID- 8146497
TI  - Clinical application of paraspinal somatosensory evoked potentials (PS-SEPs) for
      the diagnosis of spinal cord lesion.
AB  - To evaluate the clinical utility of somatosensory evoked potentials elicited by
      stimulation of the paraspinal region (PS-SEPs), waveform characteristics and
      scalp topography were studied in 23 normal controls. PS-SEPs were recorded in 22
      patients with spinal lesions, and the relation between the abnormal PS-SEPs and
      clinico-radiological findings was investigated. 1) The normal control study
      showed clear waveforms on the scalp elicited by stimulation of the paraspinal
      region from C7 to the L2 spinous process level, with both bilateral and
      unilateral stimulation. The latency of PS-SEPs was gradually decreased when
      stimulation was moved in the caudo-rostral direction. 2) The normal range of
      spinal conduction time and conduction velocity was wide. The conduction velocity
      resulting from stimulation of the lumbar region tended to be slower than that
      from stimulation of the thoracic region, perhaps due to the difference in the
      length of the peripheral cutaneous nerves. 3) There was no correlation between
      the height and the latency of PS-SEPs. 4) Amplitudes of PS-SEPs after unilateral
      stimulation of the C7 and Th5 spinous levels were larger on the scalp
      contralateral to the side of stimulation. These findings were similar to SEPs
      elicited by median nerve stimulation. There was no significant amplitude
      laterality of PS-SEPs when the Th10 and L2 spinous levels were stimulated.
      Posterior tibial nerve SEPs showed a larger amplitude at the scalp ipsilateral to
      the side of stimulation than at the contralateral side. All these findings
      suggest that the cortical generator sites of PS-SEPs elicited by C7 and Th5
      stimulation are located near the hand area, and those from Th10 and L2
      stimulation are between the hand and the foot area. 5) Unilateral stimulation
      disclosed a clear laterality of sensory disturbance that was obscure when only
      bilateral stimulation was employed. PS-SEPs showed a high degree of abnormality
      when the patient had deep sensory disturbance. Generally, abnormal PS-SEPs were
      found caudal to the clinical sensory level, and a few cases showed abnormal PS
      SEPs rostral to the sensory level. The latter might indicate that PS-SEPs
      detected subclinical sensory disturbance. It was therefore concluded that PS-SEPs
      are a useful tool for the objective evaluation of sensory disturbance, especially
      in cases of thoracic lesion, because conventional SEP studies, utilizing non
      cephalic references do not provide clear identification of abnormal sensory
      levels along the thoracic spinal cord.

PMID- 8146498
TI  - [Main household occupation and mean birth weight in Japan 1984].
AB  - By using the 1984 vital statistics released on magnet tapes by the Japanese
      government, we observed in the present study how the mean birth weight (MBW)
      varies from one group of mothers who fall under the same category of "main
      household job" to another. In so doing, we compared the MBWs among different job
      categories in terms of mother's age, baby's sex, and parity. The obtained results
      are summarized as follows: 1) The MBW of primiparae and male babies was found to
      be significantly different among the job categories in the age range of 20-39. In
      the group of multiparae and male babies, however, all the age ranges older that
      twenty showed significant differences in the MBW among the job categories. In the
      group of female babies, the significant difference was found in the age range of
      20-39 and all the ranges older than twenty for primiparae and multiparae,
      respectively. 2) The above results were considered to be caused mainly by the low
      MBW in the category of "other" for primiparae, and by the high MBW in "part-time
      farming" and the low MBW in "other" for multiparae.

PMID- 8146499
TI  - [Significance of a mass survey for colorectal cancer at the workplace].
AB  - Two thousand four hundred and forty workers from 2 plants were enrolled in a mass
      survey for colorectal cancer using a single immunological fecal occult blood test
      as screening. The occult blood test was positive in 71 (4.0%) out of 1,759
      subjects in whom the test was conducted. A further investigation, including total
      colonoscopy or barium enema, was performed on 52 (73.2%) of the 71. Colon cancer
      was detected in 5 cases: 1 with advanced cancer and 4 with early cancer (cancer
      in the adenoma). The advanced cancer was successfully resected by surgery and the
      early cancers were removed by endoscopic polypectomy. Adenomas were found in 21
      cases, 11 of which were polypectomized. From these results, it can be seen that a
      survey for colorectal cancer at the workplace is important, and by expanding the
      number of subjects for the survey in the workplace we can expect more and earlier
      detections of colorectal cancer.

PMID- 8146500
TI  - [Comparative studies on the evaluation of vibratory perception thresholds using
      three different instruments, vibratron II, TM-31A and SMV-5--reliability,
      correlation with age and interrelationship].
AB  - Vibratory perception thresholds of 40 (13 males and 27 females) subjects without
      sensory disturbances were evaluated using three different instruments, Vibratron
      II, TM-31A and SMV-5, successively three times every third or fourth day to
      compare their reliability, correlation with age and interrelationship. The
      intraclass correlation coefficients of the threshold, obtained at the palmar
      distal phalanx of the index finger of the predominant hand by using Vibratron II
      and SMV-5 were 0.77 and 0.88, respectively, and those at the radial styloid
      process on the same side by using TM-31A and SMV-5 were 0.62 and 0.84,
      respectively. There was a similarity of the intraclass correlation coefficients
      in the measurement at both sites between the subjects of ages < or = 40 and those
      of ages > 40, when different instruments were used. However, the thresholds were
      lower among the subjects of ages < or = 40 than among those of ages > 40. A
      significantly positive correlation was found between the threshold and the age at
      both sites when using different instruments. A significantly positive correlation
      was also found between the thresholds obtained by Vibratron II and SMV-5 at the
      palmar distal phalanx and between those obtained by TM-31A and SMV-5 at the
      radial styloid process. The above data indicate that each instrument is
      applicable not only for diagnosing and evaluating the vibratory sensation
      disturbances, but also for the follow-up study and evaluation of the efficacy of
      the specific treatment for the patients with sensory disturbances. They are
      likewise applicable for the screening and diagnosis of peripheral neuropathy in
      the occupational and environmental medicines. However, the reliability was lowest
      in the evaluation by TM-31A, and the correlation coefficient was smallest in the
      relationship between the age and the threshold obtained by TM-31A.

PMID- 8146501
TI  - [The effect of the odour of mother's milk and orange on the spectral power of EEG
      in infants].
AB  - Few studies have been found on the EEG responses to odours in infants. Most of
      the studies done regarding infants up until now have focused only on the
      psychological and behavioral reaction of infants to odours. The purpose of the
      present study is to investigate whether or not relative differences in EEG
      response are seen before and during the odour presentation of mother's milk and
      orange in infants, and if they do respond to these odours, are there any
      differences in the EEG responses? EEG responses to these two odours were studied
      in 11 healthy mixed fed infants aged from 3.3 to 4.2 months during sleep. Changes
      in the sleep stage 2 and slow wave sleep EEG's were analyzed by the fast Fourier
      transformation method. While the mother's milk was presented, a significant
      decrease in the amplitude of EEG was observed in the delta and theta bands in the
      bilateral frontal and central regions of the brain, but on orange odour
      presentation, an increase of delta bands was seen in the central and right
      parietal regions. Detailed statistical analysis (ANOVA) revealed that the EEG
      responses to the two odours were significantly different from each other in the
      delta and theta bands. The present results suggest that these two odours seem to
      cause a different psychophysiological change in infants.

PMID- 8146502
TI  - Effects of coenzyme Q10 on lung preservation: a study with an isolated rat lung
      reperfusion model.
AB  - We studied the effect of Coenzyme Q10 (CoQ10) on lung preservation using an
      isolated rat lung reperfusion model. After the lung of a Wistar male rat was
      flushed with a solution consisting of 40 mM phosphate buffered saline, the heart
      lung block was excised and immersed in the same solution at 10 degrees C for 6
      hours. In experiment 1, CoQ10 was added to the flushing solution. In experiment
      2, CoQ10 was injected i.v. 1 hour before the organ was harvested. After the
      preservation, both lungs were reperfused and ventilated for 30 minutes. No
      benefit was noted when CoQ10 was added to the flushing solution. However, when
      CoQ10 was pretreated one hour before harvesting, the lungs showed significantly
      better preservation in pulmonary artery pressure, airway pressure, gas exchange
      function and the wet/dry weight ratio than those of the control group. Thus,
      appropriate pretreatment of CoQ10 may have a beneficial effect on lung
      preservation.

PMID- 8146503
TI  - The respiratory health of carbon black workers--differences between Polish, west
      European and American scientific reports.
AB  - Carbon black is used as a reinforcing agent and pigment. It is often equated with
      environmental soots but actually differs from the general class of soots in terms
      of chemical, physical and biological properties. In Poland, epidemiological
      surveys indicate a possible existence of pulmonary hazards among the workers
      exposed to carbon black, although further surveys are now under way. In West
      European countries, the results of one survey do not support this, but the next
      one will be completed after 6 years. In the United States, results indicate that
      exposure to carbon black in the workplace does not increase the risks of workers
      for circulatory, respiratory and malignant morbidities. Further evaluation of the
      effect of carbon black on human health must be continued.

PMID- 8146504
TI  - Does unemployment increase the use of primary health care services?

PMID- 8146505
TI  - Unemployment, re-employment and the use of primary health care services.
AB  - OBJECTIVE: To examine the association between re-employment and the use of
      primary health care services. DESIGN: A cohort study of employed teenagers and a
      'natural experiment' among adult long-term unemployed with an intervention group
      of re-employed, a control group of not re-employed, and a matched control group
      of permanently employed. SETTING: An industrial town (pop. 25,000) in
      southwestern Finland. PARTICIPANTS: 84 teenage and 143 adult long-term unemployed
      and 82 permanently employed individuals. MAIN OUTCOME MEASURE: Frequency of
      primary health care visits. RESULTS: Primary health care visits increased during
      re-employment among both teenage and adult re-employed (n = 82), but not in a
      control group of 61 long-term unemployed who were not employed under the re
      employment scheme. A comparison with persons in regular wage employment indicated
      that visits increased from a low to a normal level. CONCLUSION: To explain the
      results, reference is made to the need for sickness absence certificates and to
      epidemiological factors. The findings also raise serious questions with regard to
      the ability of the health care system to reach, let alone help, unemployed
      citizens.

PMID- 8146506
TI  - A clinical follow up of unemployed. II: Sociomedical evaluations as predictors of
      re-employment.
AB  - OBJECTIVE: To frame and study sociomedical evaluations in clinical work with
      unemployed people. DESIGN: In a two-year follow up of routine health
      examinations, three sociomedical evaluations were set up. The first was the
      direct conclusion of the check-up, based on sickness and possibilities of
      treatment. The second dealt with work identity, and the last was a diagnostic set
      of main unemployment problem. SETTING: The four municipalities of Grenland,
      Norway. PARTICIPANTS: A representative sample aged 16 to 63 who had been
      registered with the labour market authorities for more than 12 weeks. RESULTS:
      21% of the unemployed needed further treatment. 7% were classified as
      "discouraged", being on their way out of the labour market, while the majority of
      the study group was healthy job seekers. Work identity seemed to be wage earning
      for 83%, homemaking for 9%, cultural work for 3%, and being a pensioner for 5%.
      The main unemployment problem was lack of work for 46% of the examined. Other
      problems were poor health, being less attractive workers, or having little
      courage for job search. The evaluations predicted re-employment after two years.
      They divided the unemployed in groups with from five to seven times difference in
      re-employment rate. CONCLUSION: These standardized sociomedical evaluations seen
      to be useful in clinical work with unemployed people.

PMID- 8146507
TI  - The spectrum of patients strongly influences the usefulness of diagnostic tests
      for pneumonia.
AB  - OBJECTIVE: To study the influence of the spectrum of patients on the usefulness
      of five clinical cues, "very annoying dyspnoea", "strong lateral chest pain",
      crackles, C-reactive protein analysis, and erythrocyte sedimentation rate in the
      diagnosis of pneumonia. DESIGN: Evaluating the diagnostic properties of the cues
      against radiographic pneumonia at four steps in the diagnostic process,
      associated with increasing prevalence of pneumonia: 1. in all the 581 patients
      included, 2. in 402 of these patients who underwent physical chest examination,
      3. in 188 patients classified by the doctors as having a lower respiratory tract
      infection, and 4. in 79 patients referred for radiography by the doctors.
      SETTING: The municipal emergency clinic in Tromso, Norway. PARTICIPANTS: 581
      adult patients with respiratory tract infection. OUTCOME MEASURES: Sensitivity,
      specificity, Likelihood Ratio, and Positive predictive value. RESULTS: A tendency
      of decreasing specificity and Likelihood Ratio with increasing prevalence of
      pneumonia was demonstrated for all test, except for C-reactive protein analysis.
      This tendency may be explained either by the emphasis laid on the tests by the
      doctors when selecting patients for the diagnostic steps, or by an association
      between the evaluated tests and those emphasized by the doctors. CONCLUSION: As
      the diagnostic value of symptoms and signs are strongly influenced by selection,
      caution should be shown when transferring diagnostic values from one clinical
      setting to another.

PMID- 8146508
TI  - The effect of reimbursement on the use of antibiotics.
AB  - OBJECTIVE: To examine the effect of a reduction on the reimbursement of drugs on
      the use of antibiotics by general practitioners in Denmark. DESIGN: A prospective
      study using a questionnaire comparing the results with a similar study 3 years
      before, a period with normal reimbursement. PARTICIPANTS: 553 general
      practitioners prescribed antibiotics for 5765 patients. MAIN OUTCOME MEASURE:
      Number of treated patients and choice of antibiotics. RESULTS: 7607 patients were
      treated in 1987 compared with 5765 in 1990, the relative number of patients
      treated for sinusitis, other upper respiratory tract infections, acute
      bronchitis, pneumonia and upper gynaecological infections was significantly less
      in 1990 than in 1987. Other infections, particularly those that are often
      diagnosed by culture or microscopy by the general practitioners themselves,
      increased significantly. They included tonsillitis and urinary tract infections.
      CONCLUSION: Reimbursement can be a very powerful tool controlling the use of
      antibiotics by general practitioners.

PMID- 8146509
TI  - Reproducibility and validity of a postal questionnaire. The abdominal symptom
      study.
AB  - OBJECTIVE: To find out whether it is possible to examine
      abdominal/gastrointestinal symptoms by a postal questionnaire. DESIGN: In the
      Abdominal Symptom Study a postal questionnaire was sent to a representative
      sample of adults (n = 1290) on two occasions, one year apart. The questionnaire
      was sent a third time to a subsample (n = 110), and to another sample (n = 213)
      who had not seen the questionnaire before. A subsample (n = 150 of the 1290) was
      subjected to a medical interview and examination. SETTING: The municipality of
      Osthammar, Sweden. PARTICIPANTS: A sample (9.3%) of all Swedish citizens (20-79
      yrs) in the municipality. MAIN OUTCOME MEASURE: Reproducibility and validity of a
      postal questionnaire. RESULTS: The response rate was 90%. Roughly 50% of the
      study population reported abdominal symptoms. The reproducibility of the results
      was satisfactory, as was the validity of the questionnaire evaluated by medical
      interview and examination. Non-responders did not report more symptoms than
      responders. CONCLUSION: It is possible to examine abdominal/gastrointestinal
      symptoms with a postal questionnaire. The questionnaire used in The Abdominal
      Symptom Study seems to be useful for this purpose.

PMID- 8146510
TI  - Iron supplementation in pregnancy. General practitioners' compliance with
      official recommendations.
AB  - OBJECTIVE--To compare general practitioners' routines regarding iron
      supplementation in pregnancy with national recommendations. DESIGN: Mailed
      questionnaire to general practitioners. SETTING: A county in western Norway.
      SUBJECTS: 184 general practitioners. MAIN OUTCOME MEASURES: Descriptive
      registration of reported routines regarding assessment and supplementation of
      iron. RESULTS: 11% of general practitioners reported complete adherence to the
      national programme recommending iron supplements for everyone in the second half
      of pregnancy and use of s-ferritin estimation if Hb falls below 11 g/dl. 36% of
      the doctors prescribed iron supplements routinely irrespective of iron status.
      87% reported use of s-ferritin estimation in antenatal care; usually on
      indication of low Hb, almost 20% as a routine screening in all pregnancies.
      CONCLUSION: General practitioners' compliance with national recommendations for
      iron supplementation in pregnancy is very low and probably reveals a need both
      for a review of the national recommendations and for an approach to increase
      compliance with given standards.

PMID- 8146511
TI  - "The Goteborg Quality of Life Instrument"--a psychometric evaluation of
      assessments of symptoms and well-being among women in a general population.
AB  - OBJECTIVE: To examine with psychometric analysis techniques the potential for
      constructing valid composite variables of "The Goteborg Quality of Life
      Instruments". DESIGN: Prospective population study of women in 1974-75 and in
      1980-81. SETTING: City of Goteborg, Sweden. PARTICIPANTS: Representative samples
      of the general population of women in five age strata between 44 and 66 years of
      age in 1974-75, followed 1980-81 including new cohorts of women aged 26 and 38.
      1302 women were examined in 1974-75 and 1408 in 1980-81. MAIN OUTCOME MEASURE:
      "The Goteborg Quality of Life instrument", constructed in the early 1970s to
      measure symptoms and well-being in a population study of men. RESULTS: Four multi
      item scales were identified with satisfactory reliability and validity, i.e.,
      they met defined criteria of multi-item scales and benefit from higher
      reliability than single questions. The psychological symptom scale comprised all
      ten questions intended to reflect depression and tension, while the physical
      symptom scale included all six pain questions, the general symptoms dizziness,
      breathlessness, and nausea, and general fatigue that belonged to both symptom
      scales. The social well-being scale comprises all well-being questions believed
      to reflect the broad concept of life satisfaction. The physical-mental wellbeing
      scale reflected satisfaction with both general and mental health. Several symptom
      and well-being questions were clearly outside the main clusters and should be
      treated as single items. CONCLUSIONS: Use of a few, distinct scales instead of a
      number of single questions should increase statistical power because the number
      of comparisons is greatly reduced and problems of chance findings are thus
      minimized.

PMID- 8146512
TI  - Indicators of childhood sexual abuse in gynaecological patients in a general
      practice.
AB  - OBJECTIVE: To find indicators of a history of childhood sexual abuse in patients
      consulting for a gynaecological examination in a general practice. DESIGN:
      Semistructured interview after a consultation. SETTING: General practice in the
      city of Oslo, Norway. PARTICIPANTS: Of 117 women aged 20-49 with a gynaeco-
      logical problem, 85 were interviewed. MAIN OUTCOME MEASURE: History of childhood
      sexual abuse. RESULTS: 24 (28%) of 85 women interviewed by their female GP when
      consulting for a gynaecological problem reported childhood sexual abuse. In total
      they reported 32 abusive events, quite different as to the type of assault, the
      relation to the offender, and the duration. A history of pelvic pain or
      gynaecological surgery showed a significant association with reported childhood
      sexual abuse with odds ratios of 4.0 (CI 1.0-15.8) and 4.1 (CI 1.0-17.0),
      respectively. As adverse sexual experiences may lead to somatization as a coping
      strategy, certain findings might be indicators of unknown childhood sexual abuse
      in patients presenting for gynaecological disorders. CONCLUSION: A history of
      pelvic pain and gynaecological surgery may be indicators of sexual abuse in
      childhood.

PMID- 8146513
TI  - Vaginal discharge in general practice--women's perceptions, beliefs and
      behaviour.
AB  - OBJECTIVES: To describe women's perceptions and beliefs about their vaginal
      secretion and to relate these to their behaviour with respect to complaints of
      vaginal discharge. DESIGN: A multi-practice study including questionnaires for
      women and doctors and a semi-structured interview study. SETTING: North Jutland
      County and Aarhus County, Denmark. SUBJECTS: 283 women with and 417 women without
      complaints of vaginal discharge answered a questionnaire about their vaginal
      secretion. Ten women with vaginal discharge took part in the in-depth interviews.
      RESULTS: 179/274 (65%) women with and 111/417 (27%) women without complaints of
      vaginal discharge were bothered by their usual secretion. In 54/269 (20%) women
      with complaints, the pelvic examination was normal. In 59/416 (14%) women without
      complaints, the doctor found an abnormal vaginal secretion. Most women
      complaining of vaginal discharge had an external locus of control in relation to
      their symptoms, but an internal locus of control in relation to health in
      general. Fear of having a serious disease or a sexually transmitted disease was
      the reason for the visit to the general practitioner in 164/281 (58%).
      CONCLUSION: Women's perceptions and beliefs about their vaginal secretion varied
      and were related to their health seeking behaviour. In addition to information
      about possible biological causes of vaginal discharge, the general practitioner
      should also actively seek information about the women's perception of normality
      and beliefs in relation to the symptoms she experiences.

PMID- 8146514
TI  - Symptomatic lower urinary tract infection induced by cooling of the feet.

PMID- 8146515
TI  - Validity of medical audit registrations.

PMID- 8146516
TI  - [Drug of the month. Torasemide (Torrem)].

PMID- 8146517
TI  - [Pharmacotherapy for the sake of the practicing physician].

PMID- 8146518
TI  - [How I treat... an obese patient with type 2 diabetes].

PMID- 8146519
TI  - [40 years of gerontology in Europe].

PMID- 8146520
TI  - [Theories of aging].

PMID- 8146521
TI  - [Current etiopathological hypotheses in Alzheimer's disease: contribution of
      molecular biology].

PMID- 8146522
TI  - [Cognitive aging: fatality? Failure?].

PMID- 8146523
TI  - [The young elderly and second careers. Failure of the policy of aging].

PMID- 8146524
TI  - [The riches of old age. Socioeconomic status of elderly persons].

PMID- 8146525
TI  - Use of CA 19-9 in the early detection of recurrences in colorectal cancer:
      comparison with CEA.
AB  - The serum levels of CA 19-9 were determined in the follow-up of 370 patients with
      colorectal cancer and compared with CEA. An increase in CA 19-9 preceded clinical
      diagnosis of recurrence in 25% of 72 patients. The mean time between the rise in
      CA 19-9 and clinical diagnosis of relapse was 3.7 months (median 3). Sensitivity
      of CA 19-9 in the early diagnosis of recurrence was much lower than that obtained
      for CEA (75%). Only 1 patient had elevated CA 19-9 levels and normal CEA.

PMID- 8146526
TI  - Increased plasma concentrations for type I and II tumor necrosis factor receptors
      and IL-2 receptors in cancer patients.
AB  - Using enzyme-linked immunoabsorbent assays for the soluble tumor necrosis factor
      (TNF) receptors type I (p55) and type II (p75) and IL-2 receptor we determined
      their levels in the plasma of 378 patients with various solid carcinomas, 56
      patients with benign tumors, and 241 healthy controls. The plasma concentrations
      of both TNF receptors as well as the IL-2 receptor were significantly higher in
      the cancer patients than in the healthy controls, independent of the origin or
      histology of the tumor. The incidence and the extent of the receptor increase
      correlated with the extent of the disease. In the patients with benign tumors
      plasma levels of TNF receptor p75 and IL-2 receptor were not significantly
      different from the controls.

PMID- 8146527
TI  - Aryl hydrocarbon hydroxylase activity in spontaneous mammary tumors in rat.
AB  - The development of spontaneous mammary tumors was observed for about 2 years in a
      group of 25 female Sprague-Dawley rats aged over 1 year at the beginning of the
      study. All younger females in our animal facility were similarly monitored. In
      old females, the incidence of spontaneous mammary tumors was 64%. The parity of
      rats did not protect them from tumorigenesis, but the proportion of malignant
      tumors was higher in virgin (57%) than in parous (13%) rats. Activities of
      cytochrome P450IA1-dependent enzyme (aryl hydrocarbon hydroxylase, AHH) and NADPH
      cytochrome P450 reductase (NCR) were determined in microsome fractions isolated
      from livers, lungs, uteri and tumors of rats. AHH and NCR activities in tumors
      and uteri were low compared to those in livers or lungs. In tumors, the activity
      distributions were wide, even in different tumors of the same animal the AHH
      activities varied as widely as between different animals. The activities in
      benign and malignant tumors were not statistically significantly different. No
      correlation with liver, lung or uterine activities was found either. With ageing
      of the rat, the AHH activities in tumors, liver and lungs decreased. The behavior
      of AHH in spontaneous mammary tumors in rats seems to be similar to that found in
      chemically induced tumors and seems to show individual regulation, possibly
      altered by tumorigenesis in each individual tumor.

PMID- 8146528
TI  - Factors effecting the measurement of tumor-associated MUC1 mucins in serum.
AB  - MUC1 epithelial mucins are produced by both normal and malignant epithelial
      cells. Serum proteins reactive with monoclonal antibodies against MUC1 mucins
      were studied using several techniques. Separation of proteins by native PAGE
      showed that anti-MUC1 core protein antibodies reacted with a high M(r) mucin but
      also with a 70-kD protein (p70) in normal women and women with ovarian cancer.
      After purification by gel filtration, p70 was not reactive in a double
      determinant ELISA (CASA) and only weakly reactive in an inhibition assay. Serum
      CASA levels increased during pregnancy but p70 disappeared. Neuraminidase
      treatment of serum resulted in a greater increase in CASA in normal women and in
      ovarian cancer patients with low initial CASA than in ovarian cancer patients
      with high CASA and pregnant women (p < 0.05). These findings suggest that
      pregnancy and ovarian cancer-derived mucins are less heavily sialylated than
      mucin derived from normal tissues. An inhibition assay was developed which was
      more sensitive, but provided no diagnostic advantage over CASA. MUC1 is present
      in the serum of all women, reactivity in assays utilizing core protein antibodies
      is probably dependent not only on molar concentration but on the degree of
      exposure of peptide epitopes.

PMID- 8146529
TI  - Combined use of serum enzyme levels as tumor markers in cervical carcinoma
      patients.
AB  - Enzymology has acquired a prominent place in human pathology, and serum enzyme
      investigations have become a prerequisite for various diseases, including cancer.
      Serum phosphohexose isomerase (PHI), aldolase (ALD) and alkaline phosphatase
      (ALP) levels were evaluated in 90 untreated patients with cervical carcinoma and
      84 healthy age-matched females (controls). The concentrations of the three
      enzymes were significantly raised (p < 0.001) in patients compared to the
      controls. Receiver operating characteristic curve analysis revealed higher
      sensitivities of PHI and ALP, as compared to ALD at different specificity levels
      between 60 and 95%. Combined use of PHI and ALP revealed increased sensitivity
      and specificity. Combined use of PHI, ALD and ALP revealed a greater number of
      responders with enzyme values within the normal range than nonresponders. The
      results suggest that combined evaluation of the enzymes might be helpful to
      establish a useful aid to strengthen the armamentarium currently employed in the
      diagnosis and treatment monitoring of patients with cervical carcinoma.

PMID- 8146530
TI  - Diagnostic value of tissue polypeptide specific antigen in patients with
      pancreatic carcinoma.
AB  - We evaluated the clinical utility of a new tumor marker tissue polypeptide
      specific antigen (TPS) in the diagnosis of pancreatic carcinoma. Serum
      concentrations were determined in 113 patients with jaundice, in 18 patients with
      laboratory values suggesting cholestasis and in 60 patients with suspicion of
      chronic pancreatitis or pancreatic tumor. Twenty-four of these 191 patients had
      pancreatic carcinoma and 2 patients had carcinoma of the papilla of Vater. The
      highest median serum TPS value was detected in patients with malignant liver
      disease, but high median values were also measured in patients with pancreatic
      cancer, bile duct cancer or benign liver disease. The sensitivity of TPS was
      50.0%, with a specificity of 73% and an efficiency of 70%. In comparison with
      carcinoembryonic antigen (CEA), CA 50 and CA 242, the TPS test showed lower
      sensitivity, but the differences in specificity and negative predictive value
      were considerably smaller. The utility of TPS as a complementary test was also
      analyzed. When TPS was combined with other marker tests, their specificities
      clearly improved, being highest in the combination of TPS and CA 242 (92.5%). In
      this combination, efficiency and positive likelihood ratio were also clearly
      better (85% and 5.6) than those of the marker tests alone. In conclusion, TPS
      seems less accurate than CEA, CA 50 or CA 242 in the diagnosis of pancreatic
      cancer, but because of its different nature it may be considered to be used as a
      complementary test.

PMID- 8146531
TI  - Characterization of nicotinamide methyltransferase in livers of mice bearing
      Ehrlich ascites tumors: preferential increase of activity.
AB  - There was a 2- to 7-fold increase in nicotinamide methyltransferase activity in
      the livers of mice and rats bearing seven different kinds of tumors compared with
      the respective control normal livers, while activity in the tumors themselves was
      hardly detectable. The activity in the liver started to increase markedly 3-7
      days after i.p. transplantation of Ehrlich ascites tumors into the mice,
      maintaining a plateau up to death. Metabolic conversion of 14C-nicotinamide to
      14C-N1-methylnicotinamide was 3-fold higher in the slices of the ascites tumor
      host liver than in the normal liver, but the conversion to other radioactive
      metabolites was not significantly different. Nicotinamide methyltransferase was
      finally purified 20,000-fold with a yield of 4% from the cytosolic fraction of
      the ascites tumor host liver by means of five purification steps. At every
      purification step, only one enzyme fraction was detected. The enzyme finally
      isolated exhibited a single protein band in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis, with a molecular weight of 26,000. As for the compounds
      investigated, including the substrates for methyltransferases other than
      nicotinamide methyltransferase, only quinoline could be the substrate for enzyme
      activity. It is suggested that the increase in enzyme activity in the tumor host
      liver probably derived from the endogenous enzyme preexisting in the liver before
      tumor transplantation.

PMID- 8146532
TI  - [Malignant lymphoma in children].
AB  - Malignant lymphomas of children are among the pathologies which have benefited
      the most of the improvements of therapy since twenty years. Classically, the
      therapy of Hodgkin lymphoma included radiotherapy; nowadays, the role of
      chemotherapy becomes more important. For non-Hodgkin lymphomas, the role of
      surgery and radiotherapy has quite completely disappeared, and the tumors are
      cured by chemotherapy. This review will focus on Hodgkin lymphoma, and two of the
      most frequent non-Hodgkin lymphomas, namely Burkitt lymphoma and lymphoblastic
      lymphoma. Most recent advances in treatment and management of sequelae are
      presented.

PMID- 8146533
TI  - [Neuroblastoma. Current clinical and therapeutic aspects. Contributions of modern
      biology].
AB  - Neuroblastoma is a malignant tumour of the sympathetic tissue observed in
      children, generally before 6 years and before 1 year in one-third of the cases.
      In most cases the primary tumour lies in the retroperitoneal region, and in
      particular in the adrenal gland. Metastases affect the bones and bone-marrow
      after the age of 1 year and the liver in infants. Children whose metastases are
      present at the time of diagnosis are the most numerous. The therapeutic problems
      posed by non-metastatic forms are almost exclusively due to the difficulties
      encountered in complete excision of the tumour. For this reason, tumour reduction
      by preoperative chemotherapy plays a large role in the therapeutic approach. The
      prognosis of metastatic forms is totally different in infants and in older
      children: in infants, hepatic metastases without bone lesions have a favourable
      prognosis as a rule and sometimes regress without treatment. In older children,
      the usual osteomedullary damage still has a very sombre prognosis despite the
      recent therapeutic advances due to high-dose chemotherapy with bone-marrow
      transplantation. Cytogenetic studies and molecular biology have improved our
      understanding of these differences in the outcome of the disease. Amplification
      of Nmy cellular oncogene, ploidy and chromosome 1 short-arm deletion are
      essential prognostic factors in this particular tumour.

PMID- 8146534
TI  - [Malignant cerebral tumors in children].
AB  - Malignant brain tumours (mainly medulloblastoma, glioma, and ependymoma) are the
      first cause of solid tumours in children, and a major cause of mortality from
      cancer in paediatrics. The most frequent circumstance of discovery is
      intracranial hypertension. Early and atypical signs should give the alarm and
      call for emergency neuroradiological explorations. Major therapeutic advances
      have been made in the last ten years in the fields of neurosurgery, radiotherapy
      and chemotherapy of brain tumours in children. Multidisciplinary care is now
      indispensable usually as part of multicentre cooperative clinical trials.
      Therapeutic approaches are guided by a concern not only for effectiveness, but
      also for low toxicity, in order to reduce the long-term sequelae often caused by
      irradiation of the developing central nervous system.

PMID- 8146535
TI  - [Nephroblastoma (Wilms' tumor)].
AB  - Nephroblastoma is one of the frequent tumours in children. It is the tumour that
      has most benefited from advances in chemotherapy made during the last twenty
      years, a period in which its cure rate has increased from 50 to 90%. This tumour
      is easy to diagnose by radiology and ultrasonography. Its histological features
      are now well known, and diagnostic problems have become rare. What predominates
      at present is research on the link which exists between the development of these
      tumours and certain congenital malformations on the one hand, and certain
      chromosomal anomalies on the other hand. Deletion of chromosome 11 short-arm is
      the most common of these anomalies. Nephroblastoma might be one of those tumours
      which develop due to derepression of cell proliferation. Treatment rests on
      nephrectomy and chemotherapy which nowadays consists of numerous and effective
      drugs. Radiotherapy is still used but as little as possible because of the
      sequelae it creates. Treatment has much benefited from preoperative chemotherapy
      which improves the results of the latter.

PMID- 8146536
TI  - [Osteosarcoma].
AB  - Osteosarcoma is the most frequent bone tumor in children and young adults. It
      represents 8% of all tumors in children. Pain and bone tumefaction are the
      clinical signs. Bone X ray, scintiscan, CT scan and MRN must be done before the
      biopsy which signs the diagnosis. The best treatment is chemotherapy with high
      dose methotrexate + leucovorin rescue, adriamycin, cisplatinum and ifosfamide, in
      different associations followed by surgery either conservative in 80% of the
      patients or radical. Histologic response to chemotherapy, good or bad responders,
      is the best prognostic. Postoperative chemotherapy varies with the histologic
      response; 60 to 70% of patients are living recurrence free at 5 years but
      metastases could be later.

PMID- 8146537
TI  - [Retinoblastoma].
AB  - Retinoblastoma is the most frequent malignant tumour of the eye in the child; the
      median age at diagnosis is two years. A model of carcinogenesis by two successive
      mutations has been devised for this tumour and explains the two forms of the
      disease, hereditary and non-hereditary. It is most often manifested by a whitish
      pupillary reflection (leukocoria) or internal strabismus. Funduscopy using
      general anaesthesia is used to confirm diagnosis and assess endo-ocular
      extension. When the disease is confined to the retina, local treatment
      (enucleation, radiation therapy) leads to cure in a very large majority of cases.
      When diagnosis is made early, particularly as in familial cases, conservative
      treatment is possible. In intra- and extra-retinal disease, chemotherapy and
      radiation therapy can improve prognosis.

PMID- 8146538
TI  - [Malignant neonatal tumors].
AB  - Malignant neonatal tumors are rare (2% of childhood cancers, 1-2 cases/30,000
      births). However, specificities in diagnosis and therapy must be underlined at
      this period of life; furthermore, the possibilities of antenatal sonographic
      diagnosis are improving and it may contribute to increase their incidence.
      Topographic analysis allows etiologic investigations since these tumors have the
      same diagnostic features as compared with older children, except Pepper's
      syndrome and leukemias. Therapeutic management depends on a rather good prognosis
      and fragility of such newborn. Indeed, surgical excision is the main step of
      treatment. Radiotherapy must be avoided whenever possible. Chemotherapy may be
      indicated (metastatic or unresectable tumors, omission or delay of irradiation in
      brain tumors) and has to be elaborated cautiously, according to the peculiar
      physiology of the neonate. Whatever the therapeutic strategy is, neonatal
      homeostasis must be well balanced, which implies a multidisciplinary specialized
      team. Respecting these conditions will help to cure more than the present 50% and
      better for future well being of such children.

PMID- 8146539
TI  - [Bone marrow autograft and cancer in children].
AB  - Since about 15 years intensive chemotherapy followed by autologous bone marrow
      transplantation has been used on the basis of "dose-response" principle to treat
      certain children with tumours of sombre prognosis. At present, the main
      indications for this method are metastatif neuroblastoma in less than one-year
      old children, non-Hodgkin's malignant lymphomas in partial remission or relapse,
      refractory or recurrent Hodgkin's disease and some peculiar forms of Wilms'
      tumour. In other tumours, such as rhabdomyosarcoma, Ewing's sarcoma or brain
      tumours, the indications have not yet been clearly determined. The treatment must
      be administered as part of multicentre French or European trials conducted in
      specialized centres. The practice and application of autologous bone marrow
      transplantation are being revolutionized by the availability of haematopoietic
      growth factors and the development of the peripheral blood stem cells reinjection
      technique. Genic therapy will soon have major repercussions in this field.

PMID- 8146540
TI  - [Role of surgery in pediatric oncology].
AB  - In paediatric oncology, the surgeon working in a multidisciplinary team can be
      called upon to intervene at all stages of the disease. At the time of diagnosis,
      he performs the biopsy, with or without excision of the tumour. He can also
      intervene for removal of a residual lesion or to evaluate the response after
      initial chemotherapy. He occasionally is required for metastatic surgery, or more
      rarely, for palliative surgery.

PMID- 8146541
TI  - [Management, quality of life and social rehabilitation of the child with cancer].
AB  - The aim of the treatment of a child with cancer is to reach cure without physical
      and/or psychological sequelae. The quality of life should be preserved by a
      global approach of the child and his family from the diagnosis until completion
      of treatment and follow-up periods. The specialist and the general practitioner
      should inform the child and his family on a regular basis, and check
      prospectively the tolerance of the siblings. The role of physicians also includes
      a fight for better information of public, economical and political powers, so
      that a cured child may become an happy, well integrated adult.

PMID- 8146542
TI  - [HIV detection at the beginning of pregnancy. Is it useful, is it necessary?].

PMID- 8146543
TI  - [Proton beam therapy. A major progress in radiotherapy of different tumors].

PMID- 8146544
TI  - [Rapid diagnostic tests of Streptococcus group A in pharyngitis. Value and
      limitations].

PMID- 8146545
TI  - [Weight and fertility. Complex relations not to be missed].

PMID- 8146546
TI  - [An update on uveitis].
AB  - Uveitis occurs in 0.4% of the population. Anterior uveitis is the most common
      anatomical type of uveitis (50%). HLA-B27-associated acute anterior uveitis
      represent 50% of anterior uveitis. Sarcoidosis and Behcet disease are the
      systemic diseases most frequently associated with anterior uveitis. Toxoplasmosis
      is the most frequent cause of posterior uveitis. Although the emphasis regarding
      endogenous uveitis has now shifted towards immunological, if not autoimmune
      mechanisms, infection is still believed to play a role in the development of
      disease. The initiating events probably determine the site and type of
      pathological process within the eye since the perpetuation mechanisms seem to be
      similar, at least they are mediated by CD4 T lymphocytes. These findings form the
      basic for control of the inflammatory process by immunosuppressive agents or
      immunomodulators like ciclosporin A.

PMID- 8146547
TI  - [Historical view and perspectives of the concept of vertigo].

PMID- 8146548
TI  - [Slow adrenal insufficiency. Physiopathology, diagnosis, treatment].

PMID- 8146549
TI  - [Chronic myeloid leukemia. Diagnosis, treatment].

PMID- 8146550
TI  - [Multiple sclerosis. Epidemiology, diagnosis, course, prognosis].

PMID- 8146551
TI  - [Limping in children. Diagnostic orientation].

PMID- 8146552
TI  - [Schizophrenic syndromes, autism in children. Diagnosis, course, treatment].

PMID- 8146553
TI  - [Anorexia nervosa and bulimia in adolescence. Diagnosis, treatment].

PMID- 8146554
TI  - [Kidney cancer in adults. Pathological anatomy, diagnosis, course, treatment].

PMID- 8146555
TI  - [Algodystrophies. Etiology, diagnosis, course, treatment].

PMID- 8146556
TI  - [Treatment of menopause].

PMID- 8146557
TI  - [Natural history of menopause].
AB  - Etymologically meaning "cessation of menstruation", the menopause is in fact a
      phenomenon which occurs over several years and can be divided into two phases: a
      period of "pre"-menopause, approximately from the age of 40 to 50, during which
      ovulation becomes increasingly less frequent, leads to decreased fertility and
      progesterone deficiency (luteal insufficiency), whereas the confirmed
      "menopause", which occurs between the age of 50 and 55, is the disappearance of
      all follicles, leading to estrogen deprivation. The risk associated with the
      "pre"-menopause is an "unopposed estrogen effect", with its cellular effects on
      target-tissues. The problem of confirmed menopause is decreased tissue
      trophicity, not only of the genital area, but of the body in general (skin, bone,
      blood vessels, etc.) as a consequence of estrogen deprivation. Replacement
      therapy is the logical treatment: progestins during the "pre"-menopause,
      estrogens in combination with progestins once "menopause" is confirmed.

PMID- 8146558
TI  - [Estrogens, progestins and cancer of the endometrium].
AB  - The presence of estrogens alone increases the risk of cancer of the endometrium.
      The risk increases with dosage and length of administration. Estrogens have a
      promoting rather than an initiating role since the risk progressively disappears
      after stopping treatment. Hormone-induced cancers have a better prognosis than
      spontaneous cancers. The association of progesterone or a progestogen obviates
      this risk. Prescription of oestrogens after treatment of cancer of the
      endometrium is non longer strictly contraindicated. Each case should be
      considered independently.

PMID- 8146560
TI  - [Treatment of menopause and cancer of the breast: epidemiological aspects].
AB  - Because the proportion of postmenopausal women receiving hormone replacement
      therapy is increasing, the relationship between oestrogens replacement therapy
      and breast cancer risk has important implications. Epidemiologic evidence of this
      relationship remains controversial. The available data highlight: a significant
      relative risk of breast cancer 1) after at least 15 years of oestrogen use, and
      2) in women with a family history of breast cancer or a personal history of
      benign breast disease. Most of these studies examine the association between
      breast cancer risk and equin conjugated oestrogen administered alone. In France,
      natural oestrogens are usually given associated with progestins. The consequences
      of oestrogen and progestin combinations on the risk of breast cancer need to be
      further evaluated.

PMID- 8146559
TI  - [Treatment of menopause and cancer of the breast: point of view of the
      hormonologist].
AB  - Whether or not postmenopausal estrogen-progestogen replacement therapy carries a
      risk breast cancer is a controversial subject. Very few epidemiological studies
      evaluate this risk since most of them, conducted in the United States, concern
      women treated with estrogens alone rather than combined with progestogens. The
      risk of breast cancer is high mainly when estrogens are used in high dose and for
      long periods in women with a past or present history of benign breast disease.
      The facilitating role played by oestrogens in the occurrence of benign, then
      cancerous breast diseases, is clear. Estrogens encourage cell multiplication and
      can stimulate the expression of certain oncogenes in cancerous lineages. The
      protective effect of progestogens against the risk of breast cancer is much more
      controverted. Progesterone tends to slow down the estrogen-induced cell
      multiplication and facilitates the terminal differentiation of galactophores into
      acini, the secretory structures. Two mechanisms have been characterized in normal
      mammary cells, mastopathies and hormone-dependent cancer cells: progesterone
      reduces the amount of oestradiol receptors and stimulates the activity of the 17
      beta-hydroxysteroid dehydrogenase enzyme. In view of these data, it would be
      reasonable to give postmenopausal women oestrogens in low doses and always
      combined with progestogens. Every woman with risk factors for breast cancer, such
      as a family history of breast cancer or a long past of untreated benign breast
      disease, must be carefully evaluated.

PMID- 8146561
TI  - [Estrogens, progestins and the bone].
AB  - Estrogens are the most effective agents in the prevention of post-menopausal
      osteoporosis, as witnessed by numerous epidemiological and clinical studies. They
      inhibit bone resorption by complex mechanisms, modulating the action of
      calciotropic hormones and facilitating the production by bone cells of proteinic
      factors (cytokines, bone growth factor). Recent studies suggest that estrogens
      might also stimulate bone formation directly. Moreover, synthetic progestins are
      thought to have a trophic effect on bone tissue. The effectiveness and excellent
      metabolic tolerance of the available compounds should widen the indications of
      replacement therapy in postmenopause.

PMID- 8146562
TI  - [Estrogens, progestins and glucido-lipid metabolism].
AB  - Estrogen and progestogen effects on lipid and carbohydrate metabolism are
      reviewed. Their actions depend on the type and dosage of molecules and their
      route of administration. Steroid replacement therapy in post menopausal women
      results in most cases in beneficial effect on lipids without alteration of
      carbohydrate metabolism. Therapeutic implications in women with metabolic
      disturbances as hyperlipidemia or diabetes are discussed.

PMID- 8146563
TI  - [Estrogens, progestins and vascular risks].
AB  - Animal and human studies have indicated that the progression of atherosclerosis,
      notably in the coronary vessels, is accelerated by hypo-estrogenism and slowed
      down by estrogens. The principal favourable effect of endogenous or exogenous
      estrogens is not that they modify, quantitatively or qualitatively, blood
      cholesterol: it is that they prevent cholesterol from accumulating in the
      arterial wall. This favourable effect of estrogens is completed by other
      mechanisms which modify platelet aggregation, prostacyclin/thromboxane
      equilibrium, endothelin, etc., and which improve arterial wall morphology and
      vasoactive reactions. Some synthetic progestogens, given with oestrogens for
      endometrium control, may compromise these spectacular vascular benefits, but this
      is not the case with natural progesterone. Until now, the possible risk of
      thrombo-embolism has limited the prophylactic use of hormonotherapy and imposed
      contraindications. This risk is due to imbalance in hepatic (procoagulant effect)
      and peripheral (fibrinolytic effect) stimulations and therefore is to be feared
      specifically with oral oestrogens and their hepatic first-pass effect. In the
      absence of randomized trials, it is difficult to evaluate the true importance of
      this risk in the general population or in specific high-risk groups, but several
      surveys suggest that it persists even with the minimal doses currently
      administered orally. On the other hand, there is no known theoretical risk when
      oestradiol is given parenterally, which in France is the favoured method. This
      type of replacement therapy with oestradiol should be more often prescribed to
      subjects with atherogenic hyperlipidaemia, arterial hypertension or ischaemic
      coronary disease: not only it is not contraindicated, but it should soon become
      an indication.

PMID- 8146564
TI  - [Pharmacology of estrogens used in the treatment of menopause].
AB  - Numerous compounds with estrogenic activity are available to treat menopause. The
      main ones are oestradiol, administered by various routes, and equine estrogens
      which are taken orally. These compounds differ from each other by their chemical
      structure, metabolism and kinetics; the metabolic impact of these drugs
      especially on the liver depends on these parameters. All estrogens are potent,
      active, and capable of treating effectively the short and long term
      manifestations of menopause. Their metabolic safety according to the route of
      administration remains opened to discussion.

PMID- 8146565
TI  - [Progestin treatments of menopause].
AB  - Hormone replacement therapy is prescribed to post-menopausal women in order to
      correct oestrogen deficiency and its short- or long-term consequences.
      Progestogens are combined with oestrogens to prevent the proliferative effect of
      the latter on the endometrium. There are three classes of progestogens: normethyl
      testosterone derivatives, pregnanes and norpregnanes, and natural progesterone.
      The usual choice is either natural progesterone or 17-hydroxyprogesterone
      derivatives which do not carry metabolic or vascular risks. The endometrium is
      protected by simple therapeutic rules: the doses of oestradiol must be minimal to
      prevent osteoporosis, and this product must not be administered alone for a
      sequence longer than 13 days. The progestogen sequence must last for 12 days. The
      wide range of progestogens available in France enables individual adjustments to
      be made. Using progestogens alone could be interesting in women from whom
      oestrogenic treatments are contraindicated, in view of their effect on sudden
      flush and on bone.

PMID- 8146566
TI  - [Per- and transcutaneous estrogen administration systems].
AB  - The galenical methods used for per- or transcutaneous absorption of oestradiol in
      postmenopausal women are analyzed. The role of the reservoir in case of
      transdermal systems (TTS). The advantages and disadvantages of methods using the
      skin as reservoir (open systems) and those using external systems (TTS)--are
      discussed.

PMID- 8146567
TI  - [Therapeutic scheme of menopause: criteria of choice].
AB  - The treatment of menopause must meet efficacy, safety, simplicity and
      adaptability criteria. To achieve optimal benefit-to-risk ratio, treatment must
      be instituted and followed up with consideration to 1) the patient herself and 2)
      the type of treatment: molecule, dose, route of administration, sequence,
      duration, etc. The stage of menopause must be determined, since the deficiency,
      and hence replacement therapy, involves progestins in the years just before
      menopause, and estrogens in postmenopausal women. Cellular contra-indications
      (history of breast or endometrial cancer) concern all estrogens, whereas
      metabolic or thromboembolic contra-indications concern only oral estrogens. Which
      progestin? there is a consensus in favor of progesterone or one of its close
      derivatives (dydrogesterone, pregnane or norpregnane). Continuous or
      discontinuous treatment? Discontinuous treatment, closer to normal physiology,
      causes menstrual bleeding in 15 to 20% of patients, whereas continuous treatment,
      proposed to avoid menstruations, leads to irregular bleeding in 30 to 70% of the
      cases, bleeding which calls for additional and constraining investigations, and
      would be dangerous to ignore! Among the proposed formulations, the best will be
      the one which allows for individually tailored adjustment according to signs of
      estrogen overdosage or underdosage. Treatment may be instituted at any age of
      post-menopause, and need not be limited over time, unless a contra-indication
      develops.

PMID- 8146568
TI  - [Socioeconomic stakes of menopause: evaluation of the cost-effectiveness
      studies].
AB  - The extension of hormonal replacement therapy to all women after their menopause
      as a preventive action is becoming a major public health issue. Cost
      effectiveness analysis represents an appropriate tool to address the economical
      aspects of this issue. Out of the 3 studies reported in the past recent years on
      this topic, the Oxford Hormone Therapy Group study is the only one to take into
      account all possible outcomes of the hormonal replacement therapy. Its
      conclusions, however, cannot be extended directly to other countries, as the
      hormonal replacement therapy may differ in many aspects, like: 1) the chemical
      nature, metabolism and mode of administration of the hormones used, both as
      regard the oestrogen component and the progestative one; 2) the acceptability of
      the therapy in relation to its side effects; 3) the age-specific morbi-mortality
      data in relation to hip fractures, breast cancer and cardiovascular diseases.

PMID- 8146569
TI  - [Staphylococcus aureus resistant to methicillin. Control of epidemics and endemic
      states].

PMID- 8146570
TI  - [Polyneuritis and multineuritis. Etiology, diagnosis].

PMID- 8146571
TI  - [Microscopic hematuria. Diagnostic orientation].

PMID- 8146572
TI  - [Exophthalmos. Diagnostic orientation].

PMID- 8146573
TI  - [Leg ulcer. Etiology, physiopathology, diagnosis, course, treatment].

PMID- 8146574
TI  - [Obstruction of the central artery of the retina and its branches. Etiology,
      diagnosis, course, prognosis, treatment].

PMID- 8146575
TI  - [Chronic lymphoid leukemia. Diagnosis, course, prognosis, treatment].

PMID- 8146576
TI  - [Occlusive arteriopathy of the aorta and the lower limbs of atheromatous origin.
      Diagnosis, complications, treatment].

PMID- 8146577
TI  - [Natriuretic factors of cardiac origin: renal effects].

PMID- 8146578
TI  - [Aldosterone and 11 beta-hydroxysteroid dehydrogenase: role in arterial
      hypertension].

PMID- 8146579
TI  - [Hypertension and changes in renal function].

PMID- 8146580
TI  - [Sensitivity to sodium and hypertension].

PMID- 8146581
TI  - [ACE inhibitor-diuretic combinations in the treatment of arterial hypertension].

PMID- 8146582
TI  - [Pharmacological properties and therapeutic use of the standard combination of
      hydrochlorothiazide (12.5 mg) and lisinopril (20 mg)].

PMID- 8146583
TI  - [History of glomerular filtration].

PMID- 8146584
TI  - In-the-ear and behind-the-ear hearing aids in the elderly.
AB  - A significant proportion of new hearing aid fittings are rejected by elderly
      patients. One of the reasons for this is their inability to correctly fit the
      earmould and hearing aid correctly. In this study we compared the ease of fitting
      of a behind-the-ear hearing aid with a specially modified skeleton earmould with
      an in-the-ear (ITE) hearing aid, in an elderly subject group. The modified
      skeleton earmould was found to be easiest to use. However, the ITE hearing aid
      presented handling problems only in subjects over 75 years of age. Further
      analysis of the results revealed that the majority of handling problems are found
      in female subjects in the over-75 age group.

PMID- 8146585
TI  - Tympanometry in patients with insulin-dependent diabetes mellitus.
AB  - Tympanograms were studied in 53 patients with insulin-dependent diabetes mellitus
      (IDDM) and 42 randomly selected non-diabetic control subjects, aged between 20
      and 40 years, using the Madsen Model ZO 73 Impedance Bridge. Subjects with
      abnormal tympanic membrane, conductive hearing loss and known reason for hearing
      impairment (e.g. noise damage) were excluded from the study. The mean tympanogram
      amplitudes in diabetic patients were significantly lower in both ears than those
      of control subjects. The duration of diabetes and microvascular complications
      (nephropathy and retinopathy) were associated with decreased amplitudes. These
      findings indicate that decreased tympanogram amplitudes in patients with IDDM are
      probably caused by diabetes of long duration and the microvascular complications
      associated with it.

PMID- 8146586
TI  - Clinical significance of relative probe-tone levels on distortion product
      otoacoustic emissions.
AB  - The effect of systematic variations in the relative levels (L1, L2) of two
      primary tones (f1, f2) on the amplitude of the distortion product otoacoustic
      emission (DPOAE) at 2f1-f2 and f1 < f2 was investigated in 14 ears from 7
      normally hearing human subjects. The primary tones (f2:f1 = 1.23) were
      geometrically centred at the standard clinical frequencies of 0.5, 1, 1.5, 2, 3,
      4, 6 and 8 kHz. The quantity L1-L2 was varied systematically from -10 dB through
      + 10 dB with L2 held constant at 75 dB SPL for negative values, L1 held constant
      at 75 dB SPL for positive values, and L1 = L2 = 75 dB SPL at 0 dB relative
      difference. The maximum amplitudes of the distortion products were generated when
      L1 = L2 at all geometric centre frequencies except 8 kHz. The reduction of the
      DPOAE with reduction of L1 was linear at a rate that gradually increased as a
      function of geometric mean frequency. To a lesser extent, the reduction of the
      DPOAE with reduction of L2 also was linear but at a rate that systematically
      decreased as a function of geometric mean frequency. The results suggest, that to
      maximize the level of the distortion product for clinical purposes, the relative
      levels of the primary tones should be equal to each other, at least when overall
      stimulus levels are around 75 dB SPL and f2:f1 = 1.23.

PMID- 8146587
TI  - Normative data in quiet and in noise for "DANTALE"--a Danish speech material.
AB  - For a new Danish speech material, which consists of eight word lists, normative
      speech recognition curves are presented and the equivalence of the different
      lists is examined. The normative curves were obtained in quiet and in noise using
      three scoring methods, based on 25, 75 and 80 scoring units, respectively.
      Significant subject variations were found with respect to all three scoring
      methods due to different ways of processing the perceived sounds. Based on the
      test-retest SD, the two alternative scoring methods of 75 and 80 scoring units
      were found to be slightly more reliable than the usual word score of 25 scoring
      units. The equivalence of the eight word lists was accepted in quiet. Presented
      in noise, the difference between the lists was significant due to a different
      distribution of words with an initial "s" in the word lists and a significant
      difference in the spectra of the speech and the noise in the higher frequencies.

PMID- 8146588
TI  - Absolute sensitivity measured psychophysically and using auditory steady-state
      potentials.
AB  - Absolute thresholds were measured psychophysically (behaviorally) and
      physiologically in the same subjects. Psychophysical thresholds were obtained
      using a modified method of limits. Physiological thresholds were based on
      auditory steady-state potentials recorded from the scalp. The stimuli for both
      types of test were click trains, periodic tone bursts and amplitude-modulated
      tones. The center frequency of the bursts and amplitude-modulated tones was 480
      or 2000 Hz. It was found that psychophysical thresholds improved, and
      physiological thresholds worsened as the stimulus became more frequency-specific.
      Because of this interaction, the differences between psychophysical and
      physiological thresholds increased monotonically as a function of frequency
      specificity. Physiological thresholds obtained with the low-frequency stimuli
      were lower than those acquired with the high-frequency stimuli, while
      psychophysical thresholds obtained with the two frequencies were essentially the
      same.

PMID- 8146589
TI  - Hearing aid fitting of preschool and primary school children. An evaluation using
      the insertion gain measurement.
AB  - This report presents the results of a group comparison between insertion gain
      measurements and the calculated Articulation Index (AI) in preschool children (n
      = 35), primary school children (n = 60) and adults (n = 40). Only patients with
      bilateral sensorineural hearing loss, successfully fitted binaurally with hearing
      aids, were included. Patients with an asymmetrical hearing loss or an abrupt high
      frequency loss were excluded. No statistically significant differences were found
      between the group results of the preschool children and the primary school
      children. The results showed that the overall level of insertion gain was 7 dB
      higher in the total children group (primary school and preschool children) than
      in the adult group and the AI was approximately 0.1 higher in the children group.
      Additionally, the measured insertion gain was compared to the desired gain
      resulting from prescriptive rules: it is concluded that for children the so
      called half gain rule is appropriate, while for the adults the measured insertion
      gain lies between the values prescribed by the half gain rule and the one-third
      gain rule.

PMID- 8146590
TI  - Influence of context on speech understanding ability using German sentence test
      materials.
AB  - The use of contextual information for the recognition of subsequent words may be
      considered as a central auditory process. In the present study, preliminary test
      forms of a German version of the American SPIN test were evaluated. The test
      materials consisted of short sentences with a contextual part and a final word
      that was always a monosyllabic noun. The contribution of context to the
      recognition of "high predictable" (HP) and "low predictable" (LP) final words of
      these sentences was investigated. Testing was performed in noise. However, the
      masking noise was time-weighted such that the masking level was higher for the
      final word than for the preceding contextual portion of the sentence. At scores
      of 29.3%, 50% and 70.7% correct, the mean difference in S/N ratio between HP and
      LP items was approximately 5, 5 and 2.5 dB, respectively. Equal performance for
      HP and LP items would indicate central auditory dysfunction. Possible diagnostic
      applications are discussed.

PMID- 8146591
TI  - The use of the startle reflex measurement in patients with various types of
      fixation of the ossicular chain.
AB  - The results of startle and acoustic stapedius reflex measurements can be used to
      subclassify various types of fixation of the ossicular chain. Reflex measurements
      were performed on a group of subjects with normal hearing and on a group of
      patients with surgically verified ossicular chain fixation. In 97% of the
      subjects with normal hearing (n = 30), reproducible impedance changes were
      observed as part of a startle reaction and four different reaction patterns could
      be distinguished. In a subgroup of subjects with normal hearing who had a
      relatively, statistically significant, high acoustic reflex threshold, a
      characteristic response was found which was most probably caused by contraction
      of the tensor tympani muscle only. The same response was detected in 77% of the
      patients (n = 22) with otosclerosis. In the remaining 23%, no middle ear
      impedance changes occurred as part of a startle reaction. In five out of six
      patients with fixation of the malleus, no response was observed. Although the
      startle reflex measurement is a valuable tool for distinguishing between stapes
      fixation and multiple ossicular chain fixations, the results are not conclusive.

PMID- 8146592
TI  - Hard-of-hearing pupils in ordinary schools. An analysis based on interviews with
      integrated hard-of-hearing pupils and their parents and teachers.
AB  - The primary purpose of this investigation was to establish the extent to which
      health service and educational programs complied with Norwegian legislation for
      hard-of-hearing children integrated in ordinary schools, and to describe their
      communication skills, school performance and social network development. Nineteen
      hearing aid users between the ages of 8 and 16, their parents and their classroom
      teacher were interviewed. All the pupils came from the same area in south-eastern
      Norway. The results showed that many of the children had not benefited from the
      rights to which they were entitled by law. Despite this, the hearing aid users as
      a group seemed to have a satisfactory development, especially with regard to
      speech. They seemed content with their school and class situation, especially the
      younger pupils. Greater loss of hearing often led to earlier diagnosis and,
      therefore, earlier and more adequate help. Consequently, they felt happier at
      school. Pupils with a mild loss were mainly left alone without any special
      service.

PMID- 8146593
TI  - The Nobel Lectures in Immunology. The Nobel Prize for Physiology or Medicine,
      1990. Bone marrow transplantation--past, present and future.

PMID- 8146594
TI  - Lipoxin A4 induces neutrophil-dependent cytotoxicity for human endothelial cells.
AB  - The authors have assessed the capacity of neutrophil granulocytes (PMN) to kill
      cultured human umbilical-vein endothelial cells (HUVEC) in vitro (as release of
      51Cr) in response to the recently described double dioxygenation product of
      arachidonic acid, lipoxin A4 (LXA4). LXA4 conferred a marked cytotoxicity,
      whereas formyl-methionyl-leucyl-phenylalanine (fMLP) was less potent. The LXA4
      and fMLP effects were dose dependent, with a maximum at 100 nM (which caused 2.7-
      and 2.3-fold increases of 51Cr release, respectively, relative to buffer-treated
      controls). The LXA4 and fMLP responses increased with the PMN concentration,
      depended on the fetal calf serum concentration, incubation temperature and
      duration and the presence of calcium and magnesium ions.

PMID- 8146595
TI  - Resistance and susceptibility to cyclosporin A as CD3-4-8- human thymocytes
      differentiate in vitro.
AB  - Human T-cell development appears to be relatively resistant to cyclosporin A
      (CsA). Children exposed to CsA in utero as part of kidney transplant maintenance
      have few abnormalities. The objective of the study described here was to analyse
      the effects of CsA on the development in vitro of human multinegative (MN) (CD3-4
      8-) thymocytes as a model system for thymic progenitor development in vivo. MN
      thymocytes, prepared by depletion methods, differentiated in vitro to acquire CD3
      and undergo transitions in CD45 isoform expression analogous to those postulated
      to occur in vivo. In this work MN thymocytes were cultured with IL-2 and on
      thymic epithelial cells (TEC) with or without IL-2, either in the presence or
      absence of CsA. For many thymocyte preparations, differentiation in the presence
      of CsA resulted in almost complete inhibition of the acquisition of CD3 and of
      the low Mr isoform CD45R0. Expression of CD45RA and of total CD45 were reduced
      but not eliminated and the density of CD29 was unaffected. For others, neither
      CD3 nor CD45 expression was affected, but selective inhibition of TCR delta
      expression TCR delta expression occurred. At all doses of CsA (0.1-100
      micrograms/ml), MN thymocytes continued to cycle indicating a CsA-resistant
      generative compartment. Treatment of peripheral blood T cells with CsA had no
      effect on surface expression of CD3 or CD45 isoforms but did reduce the amount of
      de novo-synthesized CD45R0 mRNA. Culture of MN thymocytes on TEC rendered them
      virtually resistant to the negative effects of CsA. CD3 acquisition was
      unhindered and total CD45 remained high, but the transition from CD45RA to CD45R0
      appeared to be delayed. In the absence of TEC, expression of both TCR alpha beta
      and of TCR delta was inhibited, but on TEC, TCR delta was actually up-regulated
      in some conditions. The effects of CsA on human thymocyte development appeared to
      be modulated by the physiological state of the donor and the growth conditions to
      which the cells were subjected. Conditions which most closely approximated those
      manifest in vivo rendered thymocytes most resistant to the negative effects of
      CsA. The amount of CsA required to affect differentiation in vitro was
      significantly higher than could be attained in vivo suggesting that the
      immunomodulatory effects of CsA in the maintenance of organ transplants may
      derive from an as yet uncharacterized mechanism.

PMID- 8146596
TI  - Characterization of a cyclosporin A-sensitive activation pathway in cultured T
      and natural killer cells.
AB  - Previously, the authors have described a molecule, identified by the LD6
      monoclonal antibody (MoAb), present at the cell surface of long-term cultured T
      and Natural Killer (NK) cells which is involved in cell triggering. In the study
      described here the authors used biotin surface labelling and immunoprecipitation
      to show that LD6 MoAb recognizes a surface protein of approximately 65 kDa. In
      combination with submitogenic concentrations of phorbol esters (PMA); LD6 MoAb
      was able to induce accumulation of mRNA specific for GM-CSF, gamma-IFN and TNF
      alpha and release of these cytokines by LD6+ T-cell lines. Both lymphokine
      production and lymphokine-specific mRNA accumulation induced by the LD6 MoAb were
      blocked totally by Cyclosporin A (CsA). To investigate the mechanism(s) of signal
      transduction through this activatory pathway, the authors performed Ca++
      mobilization experiments. The results of these experiments suggested a role for
      Ca++ in signal transduction. The Ca++ mobilization induced by LD6 MoAb cross
      linking could be inhibited totally by the use of pertussis toxin, indicating a
      possible role for G proteins in signalling through the LD6 MoAb-reactive
      molecule. Western blot analysis performed with an anti-phosphotyrosine antibody
      did not suggest that tyrosine kinase activation has a role.

PMID- 8146597
TI  - HIV-1 inhibits Leishmania-induced cell proliferation but not production of
      interleukin-6 and tumour necrosis factor alpha.
AB  - The immune response of normal human peripheral blood mononuclear cells (PBMC)
      after stimulation with human immunodeficiency virus-1 (HIV-1) antigens plus
      Leishmania donovani promastigotes in vitro was investigated. HIV-1-antigen
      stimulation of PBMC did not induce the intracellular accumulation of interleukin
      6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN
      gamma). However, cells stimulated with L. donovani antigens exhibited the
      production of IL-6 and TNF-alpha, but not IFN-gamma. Furthermore, co-stimulation
      of PBMC with HIV-1 antigen plus L. donovani resulted in the intracellular
      accumulation of IL-6 and TNF-alpha comparable to that of cells that were
      activated with L. donovani antigen alone. Heat-inactivated HIV-1 antigen did not
      appear to induce or suppress cytokine production by PBMC. However, the same HIV
      antigens did suppress L. donovani-induced proliferation as well as PPD-induced
      proliferation in a dose-dependent fashion. Elevated levels of serum cytokines
      have been demonstrated in patients with HIV infection indicating their role in
      the pathogenesis of HIV-associated immunosuppression. The results may partially
      support the idea that the abnormally increased cytokine levels in the sera of HIV
      infected subjects is due to the various opportunistic pathogens that these
      patients contract, rather than a response to HIV antigens. As cytokines have been
      shown to up-regulate HIV replication, the data suggest a role for opportunistic
      infections in cytokine-induced transactivation of HIV-1 and disease progression.

PMID- 8146598
TI  - Interactions between staphylococcal superantigens and human T-cell clones are
      predominantly but not exclusively governed by their T-cell receptor V beta usage.
AB  - Staphylococcal exotoxins (SE) are potent mitogens for human and murine T cells.
      Extensive studies in mice have demonstrated strict correlations between T-cell
      responses to individual SE and TCR V beta expression. Studies examining the TCR V
      beta expression of SE-activated human peripheral blood T cells also suggest close
      correlations, whereas the data reported using human T-cell clones (TCC) are
      conflicting. We have determined the cDNA TCRB sequences of 52 different human
      TCC, expressing 35 different T-cell receptor V beta (TCRBV)-encoded sequences.
      The TCC were tested in proliferative assays using nine different SE. Most of
      these TCC express V beta s which have not been tested previously in studies
      examining interaction between TCC and SE. The SE stimulated a variable fraction
      (1/48-31/52) of the TCC. The ability of a given SE to stimulate TCC in many cases
      correlated with V beta expression, but several exceptions were found. With one
      possible exception, comparisons between deduced amino-acid sequences within the
      'fourth hypervariable region' of the TCR beta chain and SE responsiveness did not
      reveal potential SE binding motifs. We conclude that the reactivity of T cells
      towards SE is governed mainly by their TCR V beta expression. However, the
      authors' results also suggest that the interaction between SE and human T cells
      may involve elements unidentified as yet which are in addition to the beta chain
      of the TCR.

PMID- 8146599
TI  - B- and T-lymphocyte subset numbers in the migrating lymphocyte pool of the rat:
      the influence of interferon-gamma on its mobilization monitored through blood and
      lymph.
AB  - The subset composition of the migrating lymphocyte pool is largely unknown. In
      order to determine the number of B, T, CD8+, CD4+ and CD4+ 'naive' (CD45RC+) and
      'memory' (CD45RC-) lymphocytes in this pool, the thoracic duct lymph of the rat
      was drained for 7 days. The effect of lymphocyte depletion on the number of blood
      lymphocytes was also monitored. In addition, the influence of continuously
      applied interferon-gamma (IFN-gamma) on the mobilization of the migrating
      lymphocyte pool was investigated. Within 1 week 2 x 10(9) thoracic duct
      lymphocytes (TDL) were collected, which represents about 50% of the total
      lymphocyte pool of an adult rat. Among the migrating lymphocytes an early and a
      late mobilized population could be differentiated. In the former the CD4+ 'naive'
      (CD45RC+) T lymphocytes constituted the largest population, whereas in the latter
      it was the B lymphocytes. Continuous infusion of IFN-gamma did not affect the
      number of lymphocytes in the blood. In contrast, in the thoracic duct IFN-gamma
      reduced the appearance of all lymphocyte subsets. However, the pattern of
      reduction over time differed markedly depending on the population (early or late
      mobilized) and the phenotype (B- or T-lymphocyte subsets). Thus, the migrating
      lymphocyte pool of the rat is very heterogeneous regarding its populations and
      shows complex changes in the mobilization pattern after IFN-gamma stimulation.
      Future studies should focus on how the size and the composition of the migrating
      lymphocyte pool is regulated.

PMID- 8146600
TI  - Role of T lymphocytes in experimental Staphylococcus aureus arthritis.
AB  - Using a recently developed murine model of haematogenously induced Staphylococcus
      aureus, the authors have characterized the phenotypes and functional properties
      of inflammatory cells present in the synovium of arthritic mice. The results show
      that large numbers of granulocytes and macrophages were observed in the inflamed
      synovia within 24 h of inoculation of S. aureus strain LS-1. Many of the synovial
      macrophage-like cells strained for cytoplasmic IL-1 alpha and TNF-alpha.
      Subsequently (> or = 48 h later), a prominent infiltration of T lymphocytes,
      predominantly of CD4+ phenotype, was observed. Some of the T lymphocytes stained
      for IL-2 receptor and intracytoplasmic interferon-gamma (IFN-gamma).
      Surprisingly, in spite of the severe inflammatory process, very few cells
      expressed MHC class-II molecules in the arthritic synovia. In addition, in vivo
      depletion of CD4+ T-cells resulted in a considerably milder course of
      staphylococcal arthritis. The similarities in the phenotype expression of
      synovial cells and central role of T-cells in S. aureus arthritis as well as in
      non-infectious models of arthritis, indicate that the process governing joint
      destruction is likely to be the same, irrespective of the initial stimulus.

PMID- 8146601
TI  - The multifactorial and multistage character of protective immunity to Plasmodium
      falciparum, naturally acquired by an indigenous population in Burkina Faso.
AB  - In malaria-endemic areas, protective immunity is acquired gradually. Some authors
      have proposed that different stages can be distinguished during development. To
      test this hypothesis, several in vitro assays of the host immune response to P.
      falciparum were performed in three groups of individuals: 'unprotected' children
      with clinical attacks, 'semi-immune' children, without clinical attacks but with
      transient high parasitaemias during the transmission period, and 'protected'
      adults with low residual parasitaemias. By comparison of immune responses in
      these groups and multifactorial analyses, discriminant factors and potential
      protective mechanisms were identified. Anti-RESA antibody levels were lower in
      'unprotected' than in 'semi-immune' children, while specific cellular responses,
      TNF levels and percentage of activated T lymphocytes were higher. Low humoral
      immunity and high cellular activation in children were followed by high humoral
      immunity and low cellular activation in adults. Therefore, protective immunity
      seems to pass through different stages and to result from the association of
      different immune mechanisms according to the level and duration of the individual
      experience of malaria.

PMID- 8146602
TI  - Reversible and irreversible effects of temperature on amelogenesis of hamster
      tooth germs in vitro.
AB  - Hamster first hamster molar tooth germs in early secretory stage of amelogenesis
      were cultured for one day in vitro at 6 degrees C, 22 degrees C, 37 degrees C or
      45 degrees C in the presence of 3H-proline, 45Ca and 32P-orthophosphate. Other
      explants were cultured without these labels and after culture examined by
      histology. The highest temperature tested was lethal to the explants, decreased
      total dry weight and rapidly increased total uptake of the radiolabelled mineral
      ions, probably merely due to physicochemical modification of the existing
      preculture minerals. Optimal synthesis and secretion of amelogenins were measured
      at physiological temperature (37 degrees C). Effects of exposure to both
      temperatures below the physiological value were virtually reversible when
      explants were grown at physiological temperature (37 degrees C) for another day.
      However, amelogenin secretion during this recovery period did not reach values as
      high as those found for the first day in explants initially grown at
      physiological temperature during the first day. We concluded from the four
      temperatures examined that the optimal temperature for enamel matrix deposition
      in vitro was 37 degrees C. At this temperature enamel biosynthesis and its
      secretion are high. Lowering the temperature slows down the metabolism without
      any apparent harmful effect. Normal development of the tooth explants in vitro
      resumes when the culture temperature is restored to physiological levels (37
      degrees C). For temporary storage of tooth germ explants prior to any
      reimplantation, we therefore recommend a temperature of 6 degrees C.

PMID- 8146603
TI  - Protein inhibitors of calcium salt crystal growth in saliva, bile and pancreatic
      juice.
AB  - The control of the formation of crystals in biological fluids is one of the most
      exciting field of research involving both organic and biochemical areas. Many
      organisms have evolved mechanisms which minimize or avoid the effects of
      nucleation and crystal growth formation. One of the most important mechanism is
      the interaction of specific proteins, called inhibitors, with crystals which
      alters their habits and leads to their elimination. This article, focused on
      saliva, pancreatic juice and bile, reviews our present knowledge on the structure
      function relationships existing between these proteins and their ability to
      inhibit the growth of different calcium salt crystals.

PMID- 8146604
TI  - Absence of a transcellular oxalate transport mechanism in LLC-PK1 and MDCK cells
      cultured on porous supports.
AB  - Transepithelial oxalate transport across polarized monolayers of LLC-PK1 cells,
      grown on collagen-coated microporous membranes in Transwell culture chambers, was
      studied in double-label experiments using [14C]-oxalate together with [3H]-D
      mannitol as an extracellular marker. The [14C]-labeled glucose analog alpha
      methyl-glucoside (alpha-MG) was used as functional marker for active proximal
      tubular sugar transport. Cellular uptake of oxalate and alpha-MG at both the
      apical and basolateral plasma membrane was determined. When added to the upper
      compartment, alpha-MG was actively taken up at the apical membrane, directed
      through the cells to the basolateral membrane and transported to the lower
      compartment, indicating functional epithelial sugar transport by LLC-PK1 cells.
      In LLC-PK1 cells, the uptake of alpha-MG at the apical membrane was approximately
      50 times higher than that at the basolateral membrane. In contrast to this active
      transport of sugar, LLC-PK1 cells did not demonstrate oxalate uptake either at
      the apical or basolateral plasma membrane. The apical-to-basolateral (A- > B)
      flux of oxalate in LLC-PK1 cells was identical to the basolateral-to-apical (B- >
      A) oxalate flux in these cells. Moreover these flux characteristics were similar
      to those found for D-mannitol, indicating paracellular movement for both
      compounds. From these data, it is concluded that, under the experimental
      conditions used, LLC-PK1 cells do not exhibit a specific transcellular transport
      system for oxalate.

PMID- 8146605
TI  - Ascorbic acid is an abettor in calcium urolithiasis: an experimental study.
AB  - Two sets of animal experiments using guinea pigs were planned to evaluate the
      effect of ascorbic acid supplementation on the lithogenic process. In the first
      set of experiments, 10, 40, and 60 mg doses of ascorbic acid/100g body weight/day
      were given for 105 days. Neither of the ascorbic acid doses given induced
      crystalluria, calcification or stone formation, thereby confirming our previous
      findings that ascorbic acid in the doses used by clinicians does not cause
      urolith formation. In the second set of experiments, ascorbic acid was
      supplemented in hypercalciuric (induced by calcium carbonate feeding) and
      hyperoxaluric (induced by sodium oxalate feeding) animals for 45 days. The
      results indicated that it exacerbated the calcification process in renal and
      bladder tissue.

PMID- 8146606
TI  - A review of new concepts in renal stone research.
AB  - Clinical and basic research in the field of urolithiasis has developed rapidly in
      recent years. Progress in extracorporeal shock wave lithotripsy (ESWL) and
      percutaneous nephrolithotomy (PNL) has brought about a revolution in the surgical
      treatment of urolithiasis and research at the cellular and molecular level is now
      expanding. In spite of these advances, however, clinical treatment of
      urolithiasis remains far from satisfactory. Stone recurrence in many patients
      cannot be predicted and is beyond control of urologists mainly because the
      mechanisms of stone formation are still not fully understood. It is necessary to
      study the process of stone-formation more intensely at the cellular and molecular
      level, and to strengthen the links between basic and clinical research in the
      field. In this review, the processes involved in the formation of stones are
      compared with those involved in normal bio-mineralization and a model of
      urolithiasis is put forward based on modern systems science. Attention is
      concentrated on: (a) Directions of research based on physico-chemical theories of
      stone formation; (b) The role of renal tubular defects in urolithiasis; (c) The
      role of free radical reactions in stone formation; and (d) Macromolecular
      abnormalities and their correction.

PMID- 8146607
TI  - Studies on structure of calcium oxalate monohydrate renal papillary calculi.
      Mechanism of formation.
AB  - A scanning electron microscopy study of the ultrastructure of 18 calcium oxalate
      monohydrate papillary calculi was performed with the purpose of establishing the
      main steps in calculus formation. It is concluded that these calculi originate in
      a "core" located near the central part of the calculus. Significant quantities of
      organic matter as well as calcium phosphates can be found in the "core" and at
      the surface of adhesion to the papilla and, in some cases, fibers and calcified
      tubules can also be found in the contact zone. In no case did this material
      affect the crystalline structure of the calculi, indicating that its formation
      follows the calculus genesis. The study of the compact columnar zone revealed
      that its formation starts in a practically continuous surface formed by organic
      matter and crystals that surround the core. This layer favors the growth of
      oriented calcium oxalate monohydrate crystals upon it. Based on these
      observations, a feasible mechanism of papillary calcium oxalate monohydrate
      calculus formation is proposed.

PMID- 8146608
TI  - Scanning electron microscopy of 2,8-dihydroxyadenine crystals and stones.
AB  - The lack of purine salvage enzyme, adenine phosphoribosyltransferase (APRT),
      leads to 2,8-dihydroxyadenine stone formation and/or crystalluria because it is
      insoluble in urine. Urolithiasis composed of 2,8-dihydroxyadenine is not only
      formed in a complete defect of APRT, but also in a partial deficiency of this
      enzyme. The defect is inherited as an autosomal recessive trait, the homozygous
      state is associated with high urinary levels of 2,8-dihydroxyadenine and with
      crystalluria, calculus formation, and potential nephrotoxicity. Determination of
      the APRT activity will facilitate quantification of the enzyme deficiency and
      elucidation of the hereditary history. 2,8-dihydroxyadenine excretion in the 24
      hour urine and its circadian rhythm were determined using a new method of high
      performance liquid chromatography determination. By means of a standard case
      presentation, we illustrate the analysis of urinary sediments and calculi as well
      as the scanning electron microscopic images of this kind of stone.

PMID- 8146609
TI  - Urinary calculi: review of classification methods and correlations with etiology.
AB  - Current physical and chemical methods available for urinary stones analysis are
      critically reviewed. No one method is sufficient to provide all the clinically
      useful information on the structure and composition of the stones. We show that a
      combination of refined morphological and structural examination of stone with
      optical microscopy, complemented by compositional analysis using infrared
      spectroscopy of the core, cross-section and surface of calculi, provides a
      precise and reliable method for identifying the structure and crystalline
      composition, and permits quantification of stone components while being highly
      cost effective. Using such morphoconstitutional studies leads to a classification
      of urinary stones in seven distinctive types and twenty-one subtypes among
      monohydrate (whewellite) and dihydrate (weddellite) calcium oxalates, phosphates,
      uric acid, urates, protein, and cystine calculi. Furthermore, all of the
      recognized sub-types exhibit correlations with specific pathophysiologic
      conditions. We conclude that such morphoconstitutional refined analysis and
      classification of urinary calculi is of interest to properly identify the type of
      stone disease and provides clues to etiopathogeny.

PMID- 8146610
TI  - The interaction between nephrocalcin and Tamm-Horsfall proteins with calcium
      oxalate dihydrate.
AB  - Studies of crystals of calcium oxalate dihydrate (COD) grown by vapor diffusion
      from solutions containing 5.1 x 10(-7), 1.5 x 10(-6), and 1.0 x 10(-5) M
      nephrocalcin (NC), indicate that NC profoundly affects COD's habit, size and
      structure. The decrease in COD size is such that at 1.0 x 10(-5) M NC, the
      dimensions of the crystals are reduced about five-fold with respect to those of a
      NC-free control. In addition, the planes of the (101) form disappear, the
      original habit is lost, and the diffraction pattern deteriorates to such an
      extent that only the 200 reflections are recorded. The results are quite
      different when NC is adsorbed upon rigid substrates. Under such conditions, NC
      acts as a promoter and not as an inhibitor of growth and thus nucleates COD from
      its (100) planes. Consequently, COD grows systematically juxtaposed on NC. This
      effect is highly reproducible and stereospecific. COD crystals grown by vapor
      diffusion from solutions exposed to increasing concentrations of Tamm-Horsfall
      protein (THP) exhibit a drastic decrease in COD's self-association. In sharp
      contrast with the results obtained for NC, precession photographs taken of COD
      samples exposed to 1.2 x 10(-5) M THP do not show evidence of deterioration of
      COD diffraction patterns with respect to a protein-free control. Furthermore, THP
      neither nucleates COD, nor does it appear to influence its growth or habit even
      when THP is immobilized upon a rigid substrate.

PMID- 8146611
TI  - The influence of dietary factors on the risk of urinary stone formation.
AB  - The action of various beverages and foods on the composition of the urine in the
      circadian rhythm and in the 24-hour urine has been investigated under
      standardized conditions. Orange juice leads to a significant increase of urinary
      pH and citric acid excretion. Black tea leads to a raised excretion of oxalic
      acid by only 7.9%. In the short term, beer increases diuresis, but afterwards
      leads to a compensatory antidiuresis with increased risk of stone formation.
      Depending on their composition, mineral waters have very different effects on the
      urinary constituents. Milk as well as cocoa beverage significantly increase
      calcium excretion; moreover, cocoa causes an increase in the oxalic acid
      excretion. The leafy vegetable foods containing oxalate, e.g., spinach and
      rhubarb, lead to peaks of oxalate excretion of 300-400% in the circadian
      excretion curve. Cheese leads to a significant rise of calcium excretion with
      acidification of the urine and lowering of citrate excretion. Calcium excretion
      is increased by 30% by sodium chloride. Foods containing purine result in an
      increased uric acid excretion over several days. Depending on their phytic acid
      content, brans bind calcium, but lead to an increased oxalic acid excretion.
      Analysis of the urine indicates that average diet in Germany entails a high risk
      of urinary stone formation. As a result of the change to a balanced mixed or
      vegetarian diet, according to the requirements, significant alterations in
      urinary pH, calcium, magnesium, uric acid, citric acid, cystine, and
      glycosaminoglycan excretion are measured, resulting in a drastic reduction in the
      risk of urinary stone formation.

PMID- 8146612
TI  - New methods for depositing and imaging molecules in scanning tunneling
      microscopy.
AB  - Methods and apparatus are described to deposit and image molecules by scanning
      tunneling microscopy (STM) under an inert atmosphere. Three methods of applying
      molecules have been evaluated: equilibrium adsorption from the vapor phase,
      sublimation, and electrospraying. Using these methods, a variety of organic and
      biopolymer molecules have been deposited and imaged on graphite and on gold
      (111), grown epitaxially on mica. Compared with alternatives, such as the use of
      high vacuum apparatus or glove boxes, these procedures offer some important
      advantages: they are inexpensive, convenient, and more rapid. Mercaptoethanol,
      ethanolamine, ethanol, acetic acid, and water produce two-dimensional crystalline
      adlayers on gold substrates, when they are introduced into the scanning cell as
      vapors. These adlayers are assumed to involve hydrogen bonding of the molecules
      to an oxide of gold formed on the surface. Electrospraying protein solutions on
      gold surfaces yielded images of individual protein molecules with lateral
      dimensions close to those measured by X-ray analysis, and thicknesses of 0.6-1.3
      nm. In the case of metallothionein, the known internal domain structure of the
      molecule was reproducibly observed. No detailed internal structure could be
      resolved in the other examples examined.

PMID- 8146613
TI  - Humidity effects on atomic force microscopy of gold-labeled DNA on mica.
AB  - Recent work in atomic force microscopy (AFM) of deoxyribonucleic acid (DNA) has
      relied on immobilizing DNA molecules by drying a small volume of buffered DNA
      solution onto cleaved mica. When imaging in air, relative humidity has been known
      to affect both the resolution and measured height of the DNA strands. We present
      data of measured height versus humidity for DNA and attached gold labels, and we
      propose a model for this data based on swelling of coadsorbed buffer salts upon
      exposure to moisture. In this model, small particles (e.g., DNA) stay near the
      top of the swelling salt layer, whereas larger particles (e.g., gold spheres)
      tend to be anchored down to the substrate until a moderate humidity is reached.
      At high humidity (around 65%), the salt layer becomes fluid-like and susceptible
      to tip-induced motion; the salts are either removed from the scan area or
      aggregate into island structures, depending on initial salt concentration on the
      surface.

PMID- 8146614
TI  - X-ray microanalysis of chief cells in rat parathyroid gland.
AB  - X-ray microanalysis was used to study the elemental composition of the rat
      parathyroid gland. Analyses were performed in morphologically defined cells. Use
      of semi-thin cryosections allowed us to selectively analyze cell nucleus,
      cytoplasm and occasionally dense granules in the cytoplasm. The concentration of
      elements (mmol/kg dry weight) in chief cells of parathyroid gland were as
      follows: Na 83, Mg 48, P 853, S 224, Cl 164, K 551 and Ca 10. Significantly
      higher phosphorus and potassium concentrations were found in the dense granules
      as compared to cytoplasm of the parathyroid chief cells. Choosing rat parathyroid
      gland gave the possibility to exclusively analyze chief cells. Data obtained from
      such a homogenous cell population will be of interest when studying human
      parathyroid in which chief cells are mixed together with other types of cells.

PMID- 8146615
TI  - A simple empirical calibration of energy dispersive X-ray analysis (EDXA) on the
      cornea.
AB  - Monitoring of the corneal electrolyte content is important for the study of
      chemical eye burns. This paper describes quantitative measurements on gelatin
      standards, corneas and a cornea homogenate with an energy dispersive X-ray
      analyzer (EDX) in the scanning electron microscope (SEM). Ten micrometers thick
      cryosections were freeze-dried and mounted on solid carbon supports. The applied
      quantification procedure was a local peak background analysis with a specifically
      designed computer program. Similar chemical and physical properties of gelatin,
      cornea homogenate, and cornea were proven by EDX-analysis and wet chemical
      analysis. Gelatin standards with known concentrations of different added salts
      showed linear correlations with a correlation coefficient higher than 0.95 for
      all considered elements. The local background generation on carbon supports was
      the same for gelatin standards and corneal tissue. The results demonstrate that
      quantitative EDX analysis of semi-thin samples, mounted on neutral carbon
      supports, can be reliably used for the assessment of the corneal mineral
      composition.

PMID- 8146616
TI  - Scanning electron microscopy of age-related changes in the C57BL/6J mouse
      cochlea.
AB  - Hair cells and nerve fibers inside the organ of Corti of the C57BL/6J mouse,
      which is known as the precocious presbycusis model, were studied using the
      scanning electron microscope. For this study, we used thick serial sections cut
      from celloidin blocks. In the 5-week-old mice, hair cell loss was not seen. The
      upper tunnel radial fibers crossed the upper part of the tunnel of Corti and
      entered the Nuel's space between the outer pillar cells. The fibers varied in
      diameter and showed many varicosities. The basilar fibers emerged into the tunnel
      of Corti beneath the upper tunnel radial fibers and crossed the floor of tunnel
      slightly curving basalward. The outer spiral fibers ran along the lateral wall of
      the Nuel's spaces, sometimes buried in the cytoplasm of Deiters' cells. The nerve
      endings were clearly seen on the modiolar sides of the outer hair cell bases in
      the basal turn. In the 30-, 42- and 60-week-old mice, hair cell degeneration was
      seen both at the basal and apical portions, more pronounced in the former. The
      outer hair cells were affected more than the inner hair cells. In the basal turn
      where most of outer hair cells had degenerated, the upper tunnel radial fibers
      disappeared while the basilar fibers remained. These results suggest that
      degeneration of the efferent fibers occur earlier than those of the afferent to
      the outer hair cells.

PMID- 8146617
TI  - Three-dimensional cytoskeletal structures of the chinchilla organ of Corti:
      scanning electron microscopy application of the polyethylene glycol method.
AB  - We describe the application of a polyethylene glycol (PEG) embedding technique to
      examine the sensory and supporting structures of the inner ear. The chinchilla
      organ of Corti was exposed by cracking PEG embedded cochleas. A range of PEG
      molecular weights (2000-8000) were utilized; PEG 2000, with a melting point of 57
      degrees C was preferred. After removal of the PEG, the three-dimensional aspects
      of intracellular structures were observed using scanning electron microscopy.
      Filamentous elements in the hair cell cuticular plate and in the supporting cells
      were clearly observed, as was the meshwork of cross-linked actin filaments in the
      cuticular portion of sensory hair cells. Microtubule and microfilament alignment
      patterns in pillar and Deiters cells were also clearly demonstrated.
      Characteristic structures in the outer hair cell synaptic region, such as the
      post-synaptic cistern and synaptic body, were well preserved using the PEG
      method.

PMID- 8146618
TI  - Immunological pathogenesis of endolymphatic hydrops and its relation to Meniere's
      disease.
AB  - This study was designed to investigate an immunologically induced endolymphatic
      hydrops (ELH) and to focus on the issue of its pathogenesis in relation to
      Meniere's disease. The time course of ELH was evaluated by light microscopy in a
      2-hour to 7-month period following direct antigen challenge to the endolymphatic
      sac (ELS) in systemically pre-sensitized guinea pigs. ELH began to appear in the
      vestibule and the basal turn 5-7 hours after inner ear challenge and developed
      gradually. During the interval from the second day to the first week, ELH rapidly
      developed in all the cochlear turns and reached a maximum size. During the period
      from the second week to the eighth week, ELH gradually reduced. After 9 weeks,
      ELH of the saccule and the cochlea gradually recurred. During the interval from
      the first week to the eighth week, the time course of ELH correlated well with
      the grade of cellular infiltration of the perisaccular tissue. These results
      suggest that recurrent immunological reaction in the ELS may result in disorders
      of the ELS which finally lead to the onset of Meniere's disease.

PMID- 8146619
TI  - Contributions of electron microscopy to the study of the hypertrophic scar and
      related lesions.
AB  - Prior to 1969, only one study of the hypertrophic scar had been done using
      electron microscopy, and that one used electron diffraction. Since that time,
      studies using scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM) have been integral in establishing not only the characteristics
      of this lesion but in formulating the reasons why the scar develops and how it
      resolves. The first SEM studies demonstrated a homogeneous, dense dermal matrix
      which supported the conclusion that the hypertrophic scar and keloid reflected
      excess collagen. These same studies were integral in identifying the collagen
      nodule as the basic anatomical unit of these lesions. SEM and TEM studies have
      been complimentary. The TEM studies revealed the first evidence of the phenomenon
      of occluded microvessels; but, their significance was not established until later
      quantitative studies. A hierarchy of fibroblasts was first demonstrated by TEM.
      Later, evidence came from several different investigators, through tissue culture
      and molecular differentiation, that the previously observed different electron
      microscopic features may reflect different fibroblast types of cells. Finally,
      the degenerative (or apoptotic) events, involving fibroblast-type cells and
      microvessels have been revealed by TEM studies, and supported by SEM
      observations. This phenomenon has been presented as a major factor in formation
      of the nodules, and, also, in the natural resolution of the hypertrophic scar and
      keloid.

PMID- 8146620
TI  - Scanning electron microscopy of human esophageal mucosa in patients with
      carcinoma of the esophagus.
AB  - Specimens taken at surgery from 15 patients with carcinoma of the esophagus were
      examined with scanning electron microscopy. Nine patients were treated with
      chemotherapy (cisplatin + 5-fluorouracil), surgery and radiotherapy; one received
      preoperative radiotherapy only; and the remaining five primary surgery only.
      Scanning electron microscopy was performed on specimens of both tumor tissue and
      the mucosa at least 5 cm from the tumor. In adjacent non-tumor tissue, damage due
      to treatment was observed in the form of changes in microridges and increased
      cell loss. In tumor tissue, the degree of damage was correlated to tumor response
      to treatment. For patients with no residual tumor after treatment, the
      ultrastructure was normalized with a low tumor score, while for patients with
      residual tumor, the score was high.

PMID- 8146621
TI  - Morphological characterization of the radiation sensitive cell line, xrs-5.
AB  - Morphometric analysis was performed on the radiation sensitive Chinese hamster
      ovary (CHO) xrs-5 cell line, reverting xrs-5 cells and parental K1 cells. Several
      ultrastructural parameters (increased nuclear envelope membrane separation, cell
      and nuclear volume, nuclear to cytoplasmic ratio, and the nuclear surface area
      per unit volume of the cell) were measured and correlated with radiation
      sensitivity. A trend in increased cell size and radiosensitivity was observed.
      However, only the substantially increased nuclear envelope membrane separation in
      sensitive xrs-5 cells significantly correlated with radiation sensitivity. The
      maximal nuclear envelope membrane separation in sensitive xrs-5 cells was 270.8
      nm. The maximal K1 cell nuclear envelope membrane separation was 134.8 nm,
      although, on average the K1 cell nuclear envelope membrane separation was 36.8
      nm. The reverted xrs-5 cells had a smaller nuclear envelope membrane separation
      (maximal 83.6 nm), but the measured space did not completely revert to that for
      K1 cells. Therefore, we conclude that the nuclear envelope membrane separation is
      correlated with radiation sensitivity of xrs-5 cells, but it cannot be considered
      as the only defect correlatable with the radiation sensitivity.

PMID- 8146622
TI  - Rabbit and human non-keratinising stratified squamous oesophageal epithelium
      displays similar microridge structure by scanning electron microscopy.
AB  - Since the oesophageal epithelium of common laboratory animals, rats and mice, is
      keratinized it is unsuitable for comparison with typical non-keratinized
      stratified squamous human epithelium. It is thus important to find a suitable
      animal model for the study of human oesophageal tissue changes. This study
      investigated the microridge structure of immature and adult rabbit specimens, and
      adult human biopsies by scanning electron microscopy and morphometry. The
      investigation revealed a similarity between typical squamous human and adult
      rabbit oesophageal mucosal epithelium. While human epithelium specimens
      subdivided into two other groups (non-typical squamous and non-squamous); all
      typical squamous human biopsies were from patients who had normal endoscopy
      reports and no reflux symptoms. The surface cells of typical squamous human
      epithelium displayed complex microridge patterns (64% of cell surface) but
      patterns in non-typical squamous specimens were more variable (38%) (P < 0.001)
      and cell boundaries less obvious. Rabbit squames displayed clear microridge
      patterns with an elevation in the percentage of cell surface covered by
      microridges, with increasing age, from immature to adult specimens (P < 0.001).
      There was no statistically significant differences between adult rabbit, and
      'typical squamous' human biopsies (range 51-65%), results which suggest potential
      use of a rabbit model to study changes in human oesophageal tissue.

PMID- 8146623
TI  - High resolution electron microscopy of the junction between enamel and dental
      calculus.
AB  - Newly formed dental calculus grows on the enamel surface after the tooth crown is
      exposed to the oral environment. In order to demonstrate the crystal coherence,
      the junction between enamel and dental calculus was examined in the high
      resolution electron microscope. Ultrathin sections were also used for selected
      area electron diffraction to reveal any newly formed mineral phase. High
      resolution electron microscopy (HREM) revealed that lattice fringes of dental
      calculus crystals directly coincided with those of enamel crystals. Two types of
      coherence were identified at the junction: in one type, a dental calculus crystal
      contacted the side of an enamel crystal; in the other type, the former contacted
      the tip of the latter. Tilt boundaries between lattice striations showed varying
      degrees of curvatures in contact levels. A dislocation of lattice striations was
      also observed at the junctional regions. Selected area electron diffraction
      patterns of dental calculus were almost consistent with hydroxyapatite (OH-AP).
      These findings indicate that the elongation and/or enlargement of lattice fringes
      of calculus crystals during their growth brings direct coherence with enamel
      crystals. This suggestion is supported by the fact that it is clinically
      difficult to completely remove the dental calculus without the loss of the
      superficial layer of enamel.

PMID- 8146624
TI  - Scanning electron microscopic examination of intracanal wall dentin: hand versus
      laser treatment.
AB  - Conventional cleaning and shaping of root canal spaces involves the use of hand
      and rotary instruments with irrigation. The procedure results in the formation of
      a smear layer consisting of dentin shavings, organic tissue remnants and
      microorganisms. The laser has been suggested as an aid in root canal preparation.
      In this study, pulsed and continuous wave 1.06 microns wavelength Nd:YAG lasers
      were used to compare their abilities to clean and shape root canal spaces to
      conventional methods. After preparation, the test teeth were sectioned
      longitudinally and examined by scanning electron microscopy. The results
      demonstrated that the laser was capable of removing the smear layer in its
      entirety and could occasionally alter dentin walls.

PMID- 8146625
TI  - Evaluation of erbium:YAG laser radiation of hard dental tissues: analysis of
      temperature changes, depth of cuts and structural effects.
AB  - Temperature elevations, depths of cuts and structural changes produced by 2.94
      micron pulsed Erbium:YAG laser radiation of hard dental tissues, at different
      power levels and exposure times of the laser, were studied. The depth of cut
      produced was found to vary significantly as a function of power level and
      exposure time on dry teeth. The mean temperature rise with laser radiation was
      also influenced both by power level and time of exposure. The effect of water
      flow on the teeth during laser exposure was evaluated; the results indicate that
      the ablation efficiency was better, temperature elevations lower and structural
      changes minimal to absent in the presence of water as compared to teeth that were
      dry during laser radiation.

PMID- 8146626
TI  - Observations on the enamel of odontomas.
AB  - The morphological study of odontomas provides an alternative model for observing
      the formation of dental tissues, since different maturing stages are present
      simultaneously. Investigations were performed on decalcified samples (using light
      microscopy and transmission electron microscopy) and on undecalcified samples of
      complex odontoma enamel (using transmission electron microscopy). Simultaneous
      presence of prismatic enamel at various maturing stages with different structural
      characteristics was observed. Such enamel was sometimes associated with layers of
      ameloblastic cells with characteristics of cells in functional activity. In other
      sites, the enamel did not present a prismatic structure but it appeared as
      unstructured material clusters with abundant organic component. It was concluded
      that the theory according to which an ecto-mesenchymal inductive failure occurs
      in odontomas is not confirmed. The defect seen at the beginning of the
      differentiated and anomalous tissue maturation may be related to latest events in
      the development of the enamel organ. In this regard, it was concluded that such
      events involve the efficiency of the ameloblasts and the possible alterations in
      the organic matrix.

PMID- 8146627
TI  - [Diagnosis and therapy of diarrhea].
AB  - Diarrhea is still one of the most frequent causes of death and poses many
      diagnostic and therapeutic problems. Whereas the etiology of acute diarrhea is
      mainly infectious, the cause of chronic diarrhea is much more multifarious and
      thus more difficult to diagnose. The etiology of acute diarrhea as well as the
      sense and nonsense of diagnostic procedures and therapeutic possibilities are
      discussed. A rational and practical concept for evaluation of chronic diarrhea is
      presented.

PMID- 8146628
TI  - [Current developments in the diagnosis and therapy of Crohn disease and
      ulcerative colitis].
AB  - The etiology and pathogenesis of idiopathic chronic-inflammatory bowel diseases,
      i.e. Crohn's disease and ulcerative colitis, are still unknown. This has no
      effect on diagnosis, yet does affect treatment of these diseases, which has thus
      remained symptomatic. Clinical features, laboratory findings, endoscopy in
      conjunction with histologic examination and radiologic studies are all of proven
      value in the diagnosis of these disorders. Microbiologic and, if indicated,
      serologic studies are employed to search for colitis caused by microorganisms.
      Other bowel disorders to be considered in differential diagnosis include
      ischemic, radiation and drug-induced forms of colitis, as well as diverticulitis.
      More recently introduced techniques for the detection of secondary intra
      abdominal processes are CT-scan and MRI (magnetic resonance imaging). Ultrasound
      examination of the abdomen can be used to search for thickening of the bowel
      wall. Use of the rather complicated hydrocolon sonography is rarely necessary.
      Endo-sonography is an established method for exploration of the rectum and is
      particularly useful for the detection of abscesses. The role of this technique in
      the diagnosis of colon processes remains to be determined. Studies using
      radiolabeled leukocytes are of theoretical interest but not usually required in
      the routine work-up of such patients. The same is true of chemical analyses of
      the feces and testing for antineutrophil cytoplasmic antibodies. Standard
      systemic treatment is based on the administration of salicylic acid derivatives
      and corticosteroids. Azathioprine and 6-mercaptopurine can be used in patients
      refractory to standard treatment. Metronidazole has been proven quite effective
      in patients with Crohn's disease of the colon, particularly in the perianal
      region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146629
TI  - [Colorectal carcinoma: screening and prevention].
AB  - Efficient screening for colorectal carcinoma is urgently needed because of its
      high incidence and its notoriously poor postoperative prognosis. At present only
      earlier diagnosis at a better prognostic stage will improve 5-year survival
      rates. Currently available means of detecting colorectal neoplasia and special
      risk populations are presented. Gastroenterological and oncological groups in the
      USA and Europe have put forward recommendations for 5-yearly flexible
      sigmoidoscopy for each person aged 45 years or over, a desirable yet unrealistic
      demand in view of limited financial and manpower resources. This paper therefore
      attempts to identify the various risk groups and to attribute to them
      individually an appropriate screening policy. For the normal general population
      with no specific risk factors in its personal or family history, yearly fecal
      occult blood testing remains the cheapest and most widely available minimal
      program, although current evidence indicates that this test misses over half of
      colonic malignancies (and even more benign adenomas). Special risk groups must be
      included in colonoscopy surveillance programs. Choice of the screening method for
      a given patient is usually the responsibility of the primary physician. The main
      hope for improving the present unsatisfactory situation stems from recent
      spectacular advances in molecular biology, which has discovered a number of tumor
      suppressor genes and oncogenes. If attempts at broad clinical identification of
      these chromosomal factors are successful, better determination of the risk of any
      given individual patient, and hence improved assignment of the adequate screening
      method, will be possible.

PMID- 8146630
TI  - [Follow-up of colorectal cancers].
AB  - Recurrence of colorectal carcinoma after curative surgery amounts to 30-40%. It
      is more frequent with deep penetration of the cancer, in young or old patients
      and in high risk groups. Familial polyposis, ulcerative colitis, Lynch's
      syndromes, and past history of adenoma or cancer are the best examples. The
      follow-up is effective if strict protocols are used, with frequent examinations.
      However, they are costly in comparison with results. Colonoscopy is essential for
      surveillance of the large bowel. Clinical evaluation, ultrasonography and CEA are
      useful for extra-colonic deposits.

PMID- 8146631
TI  - The changing scene in postgraduate training in the UK. A personal view from the
      chairman of the JCHMT.

PMID- 8146632
TI  - Vaccination for foreign travel--a growing need.

PMID- 8146633
TI  - Reduction in coronary heart disease--cautious optimism.

PMID- 8146634
TI  - Cold climate is an important factor in explaining regional differences in
      coronary mortality even if serum cholesterol and other established risk factors
      are taken into account.
AB  - Earlier studies have shown a strong regional association between cold climate and
      coronary mortality in Sweden and that coronary mortality is more strongly
      associated with cold climate than with other explanatory factors such as drinking
      water hardness, socioeconomic factors, tobacco and sales of butter. To examine
      the joint impact of these factors and to investigate regional differences in
      serum cholesterol and their relation to cold climate and coronary mortality,
      regression analyses were performed with 259 municipalities in Sweden as units.
      Mortality from acute myocardial infarction in men aged 40-64 during 1975-1984 was
      used as the dependent variable. A cold index was calculated, this index and the
      above mentioned factors were used as explanatory variables. The main results
      were: Cold index was the strongest factor when introduced into a multiple
      regression model. Four other strong factors had to be used to obtain the same
      explanatory strength as cold index did alone, and even when introduced as the
      last factor, cold index increased the coefficient of determination substantially.
      In a subsample of 37 municipalities, serum cholesterol was not significantly
      associated with coronary mortality. However, there was a significant correlation
      between cold index and serum cholesterol.

PMID- 8146635
TI  - Measurement and management of cardiovascular risk factors--is screening
      worthwhile?
AB  - Coronary heart disease has been described as Scotland's national disease and ways
      of reducing its incidence are therefore of paramount importance especially in
      younger males. A recent British Medical Journal paper has indicated that general
      practitioners can make little impact on patients' lifestyles. This paper shows
      that a cohort of Scottish men (Social Class III-V) responded well (80%) to offers
      of screening for risk factors of CHD, continued to attend for review and showed
      highly significant changes in their risk factor profiles. A committed
      enthusiastic primary care team have shown the potential for reducing coronary
      risk factors in so-called healthy men.

PMID- 8146636
TI  - Motor neuron disease: a disease of old age.
AB  - There is little information dealing specifically with motor neuron disease (MND)
      in the elderly. Given current epidemiological trends, geriatricians will be
      increasingly called upon to diagnose and manage this condition. We report four
      patients who presented within a six month period to a geriatric medical unit, and
      place this experience in the perspective of 229 patients from a population-based
      study of adult-onset MND in Scotland in 1989 and 1990. In 1990 Scotland had a
      crude annual incidence of MND of 2.25/100,000; the figure for those over 65 is
      four times greater. MND is more common in men, but the sex ratio was nearly equal
      over the age of 65. The risk of presenting with bulbar palsy was greater in
      women, and even higher in elderly women. This, together with increasing age, is
      the most important negative prognostic factor in MND. Problems with the diagnosis
      and management of MND in the elderly are highlighted.

PMID- 8146638
TI  - The collapse of toilets in Glasgow.
AB  - Three cases are presented of porcelain lavatory pans collapsing under body
      weight, producing wounds which required hospital treatment. Excessive age of the
      toilets was implicated as a causative factor. As many toilets get older episodes
      of collapse may become more common, resulting in further injuries.

PMID- 8146637
TI  - Computed tomography (CT) appearances of acute pancreatitis presenting as
      polyarthropathy with subcutaneous fat necrosis.
AB  - A case of severe acute pancreatitis presenting with polyarthropathy and
      subcutaneous nodules but no abdominal pain is described. Abdominal CT showed
      multiple subcutaneous soft tissue densities which on histological examination
      were identified as areas of fat necrosis consistent with pancreatic disease. Such
      CT appearances have not been described previously.

PMID- 8146639
TI  - A local census of dementia sufferers.
AB  - The results of a census of all dementia sufferers known to institutional and
      community services in Angus are reported. A total of 859 sufferers were
      identified compared with an expected 1013 based on EURODEM prevalence rates.
      After allowing for cross-boundary flow to institutions, it was estimated that the
      true identification rate was 80% (809/1013). Of the estimated total 1063
      sufferers (including cross-boundary flow): 26% were in hospital, 27% in
      residential or nursing homes, 27% in the community and known to services (often
      the GP), and 19% in the community and not known to services (or, at least, not
      returned by them in the census). With the co-operation of all concerned, a census
      approach can yield useful information at a much lower cost than a full survey.

PMID- 8146640
TI  - Elementary Scots. The discovery of Strontium.
AB  - The element Strontium takes its name from the village of Strontian in Argyll. It
      was in ore samples taken from lead mines near the village that Strontium was
      first identified as a new element in 1970. A radioactive form of the element has
      reached medical prominence through its use in the palliation of pain in patients
      with painful skeletal metastases.

PMID- 8146641
TI  - Chemicals: perceptions versus facts.

PMID- 8146642
TI  - A National Institute for the Environment.

PMID- 8146643
TI  - Smallpox virus: better to store?

PMID- 8146644
TI  - Elephant man's disease.
AB  - On the page of illustrations accompanying the review of Ann Shelby Blum's
      Picturing Nature (10 Dec., p. 1753), the caption for the illustration from Thomas
      Say's American Conchology (lower left) erroneously included the names of species
      not represented in the plate reproduced; all four specimens shown represent
      Paludina decisa.

PMID- 8146645
TI  - The hand on your purse strings.

PMID- 8146646
TI  - Nicotine research. Key study unveiled--11 years late.

PMID- 8146647
TI  - SIDS paper triggers a murder charge.

PMID- 8146648
TI  - Trail of toxins leads through conference rooms in Dallas.

PMID- 8146649
TI  - Leroy Hood: thinking big in Seattle.

PMID- 8146650
TI  - Science in the national interest.

PMID- 8146651
TI  - Self-organization in living cells.

PMID- 8146652
TI  - The evolution of genetic intelligence.

PMID- 8146653
TI  - Neural mechanisms for forming a perceptual decision.
AB  - Cognitive and behavioral responses to environmental stimuli depend on an
      evaluation of sensory signals within the cerebral cortex. The mechanism by which
      this occurs in a specific visual task was investigated with a combination of
      physiological and psychophysical techniques. Rhesus monkeys discriminated among
      eight possible directions of motion while directional signals were manipulated in
      visual area MT. One directional signal was generated by a visual stimulus and a
      second signal was introduced by electrically stimulating neurons that encoded a
      specific direction of motion. The decisions made by the monkeys in response to
      the two signals allowed a distinction to be made between two possible mechanisms
      for interpreting directional signals in MT. The monkeys tended to cast decisions
      in favor of one or the other signal, indicating that the signals exerted
      independent effects on performance and that an interactive mechanism such as
      vector averaging of the two signals was not operative. Thus, the data suggest a
      mechanism in which monkeys chose the direction encoded by the largest signal in
      the representation of motion direction, a "winner-take-all" decision process.

PMID- 8146654
TI  - Morphological bifurcations involving reaction-diffusion processes during
      microtubule formation.
AB  - Nonlinear chemically dissipative mechanisms have been proposed as providing a
      possible underlying process for some aspects of biological self-organization,
      pattern formation, and morphogenesis. Nonlinearities during the formation of
      microtubular solutions result in a chemical instability and bifurcation between
      pathways leading to macroscopically self-organized states of different
      morphology. The self-organizing process, which contains reactive and diffusive
      contributions, involves chemical waves and differences in microtubule
      concentration in the sample. Patterns of similar appearance are observed at
      different distance scales. This behavior is in agreement with theories of
      chemically dissipative systems.

PMID- 8146655
TI  - Binding and suppression of the Myc transcriptional activation domain by p107.
AB  - An amino-terminal transactivation domain is required for Myc to function as a
      transcription factor controlling cell proliferation, differentiation, and
      apoptosis. A complementary DNA expression library was screened with a Myc fusion
      protein to identify proteins interacting with this domain, and a clone encoding
      the Rb-related p107 protein was isolated. The p107 protein was shown to associate
      with Myc in vivo and to suppress the activity of the Myc transactivation domain.
      However, mutant forms of Myc from Burkitt lymphoma cells, which contain sequence
      alterations in the transactivation domain, were resistant to p107-mediated
      suppression. Thus, disruption of a regulatory interaction between Myc and p107
      may be important in tumorigenesis.

PMID- 8146656
TI  - Related target enhancers for dorsal and NF-kappa B signaling pathways.
AB  - Drosophila dorsoventral (DV) patterning and mammalian hematopoiesis are regulated
      by related signaling pathways (Toll, interleukin-1) and transcription factors
      (dorsal, nuclear factor-kappa B). These factors interact with related enhancers,
      such as the rhomboid NEE and kappa light chain enhancer, that contain similar
      arrangements of activator and repressor binding sites. It is shown that the kappa
      enhancer can generate lateral stripes of gene expression in transgenic Drosophila
      embryos in a pattern similar to that directed by the rhomboid NEE. Drosophila DV
      determinants direct these stripes through the corresponding mammalian cis
      regulatory elements in the kappa enhancer, including the kappa B site and kappa E
      boxes. These results suggest that enhancers can couple conserved signaling
      pathways to divergent gene functions.

PMID- 8146657
TI  - Recombination in adaptive mutation.
AB  - The genetic requirements for adaptive mutation in Escherichia coli parallel those
      for homologous recombination in the RecBCD pathway. Recombination-deficient recA
      and recB null mutant strains are deficient in adaptive reversion. A hyper
      recombinagenic recD strain is hypermutable, and its hypermutation depends on
      functional recA and recB genes. Genes of subsidiary recombination systems are not
      required. These results indicate that the molecular mechanism by which adaptive
      mutation occurs includes recombination. No such association is seen for
      spontaneous mutation in growing cells.

PMID- 8146658
TI  - Isolation of S. cerevisiae snRNPs: comparison of U1 and U4/U6.U5 to their human
      counterparts.
AB  - Small nuclear ribonucleoprotein (snRNP) particles are essential for pre-messenger
      RNA splicing. In human HeLa cells, 40 proteins associated with snRNPs have been
      identified. Yet, the function of many of these proteins remains unknown. Here,
      the immunoaffinity purification of the spliceosomal snRNPs U1, U2, U4/U6.U5, and
      several nucleolar snRNP species from the yeast Saccharomyces cerevisiae is
      presented. The U1 and U4/U6.U5 snRNPs were purified extensively and their protein
      composition and ultrastructure analyzed. The yeast U1 snRNP is larger and
      contains three times more specific proteins than its human counterpart. In
      contrast, the size, protein composition, and morphology of the yeast and the
      human U4/U6.U5 snRNPs are significantly similar. The preparative isolation of
      yeast snRNPs will allow the cloning as well as genetic and phylogenetic analysis
      of snRNP proteins which will accelerate our understanding of their function.

PMID- 8146659
TI  - Mutational isolation of a sieve for editing in a transfer RNA synthetase.
AB  - Editing reactions are essential for the high fidelity of information transfer in
      processes such as replication, RNA splicing, and protein synthesis. The accuracy
      of interpretation of the genetic code is enhanced by the editing reactions of
      aminoacyl transfer RNA (tRNA) synthetases, whereby amino acids are prevented from
      being attached to the wrong tRNAs. Amino acid discrimination is achieved through
      sieves that may overlap with or coincide with the amino acid binding site. With
      the class I Escherichia coli isoleucine tRNA synthetase, which activates
      isoleucine and occasionally misactivates valine, as an example, a rationally
      chosen mutant enzyme was constructed that lacks entirely its normal strong
      ability to distinguish valine from isoleucine by the initial amino acid
      recognition sieve. The misactivated valine, however, is still eliminated by
      hydrolytic editing reactions. These data suggest that there is a distinct sieve
      for editing that is functionally independent of the amino acid binding site.

PMID- 8146660
TI  - Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands.
AB  - Most human peripheral blood gamma delta T lymphocytes respond to hitherto
      unidentified mycobacterial antigens. Four ligands from Mycobacterium tuberculosis
      strain H37Rv that stimulated proliferation of a major human gamma delta T cell
      subset were isolated and partially characterized. One of these ligands, TUBag4,
      is a 5' triphosphorylated thymidine-containing compound, to which the three other
      stimulatory molecules are structurally related. These findings support the
      hypothesis that some gamma delta T cells recognize nonpeptidic ligands.

PMID- 8146661
TI  - Telomere-led premeiotic chromosome movement in fission yeast.
AB  - The movement of chromosomes that precedes meiosis was observed in living cells of
      fission yeast by fluorescence microscopy. Further analysis by in situ
      hybridization revealed that the telomeres remain clustered at the leading end of
      premeiotic chromosome movement, unlike mitotic chromosome movement in which the
      centromere leads. Once meiotic chromosome segregation starts, however,
      centromeres resume the leading position in chromosome movement, as they do in
      mitosis. Although the movement of the telomere first has not been observed
      before, the clustering of telomeres is reminiscent of the bouquet structure of
      meiotic-prophase chromosomes observed in higher eukaryotes, which suggests that
      telomeres perform specific functions required for premeiotic chromosomal events
      generally in eukaryotes.

PMID- 8146662
TI  - Requirement for the yeast gene LON in intramitochondrial proteolysis and
      maintenance of respiration.
AB  - The role of protein degradation in mitochondrial homeostasis was explored by
      cloning of a gene from Saccharomyces cerevisiae that encodes a protein resembling
      the adenosine triphosphate (ATP)-dependent bacterial protease Lon. The predicted
      yeast protein has a typical mitochondrial matrix-targeting sequence at its amino
      terminus. Yeast cells lacking a functional LON gene contained a nonfunctional
      mitochondrial genome, were respiratory-deficient, and lacked an ATP-dependent
      proteolytic activity present in the mitochondria of Lon+ cells. Lon- cells were
      also impaired in their ability to catalyze the energy-dependent degradation of
      several mitochondrial matrix proteins and they accumulated electron-dense
      inclusions in their mitochondrial matrix.

PMID- 8146663
TI  - Soluble beta-amyloid induction of Alzheimer's phenotype for human fibroblast K+
      channels.
AB  - Although beta-amyloid is the main constituent of neurite plaques and may play a
      role in the pathophysiology of Alzheimer's disease, mechanisms by which soluble
      beta-amyloid might produce early symptoms such as memory loss before diffuse
      plaque deposition have not been implicated. Treatment of fibroblasts with beta
      amyloid (10 nM) induced the same potassium channel dysfunction previously shown
      to occur specifically in fibroblasts from patients with Alzheimer's disease-
      namely, the absence of a 113-picosiemen potassium channel. A tetraethylammonium
      induced increase of intracellular concentrations of calcium, [Ca2+]i, a response
      that depends on functional 113-picosiemen potassium channels, was also eliminated
      or markedly reduced by 10 nM beta-amyloid. Increased [Ca2+]i induced by high
      concentrations of extracellular potassium and 166-picosiemen potassium channels
      were unaffected by 10 nM beta-amyloid. In Alzheimer's disease, then, beta-amyloid
      might alter potassium channels and thus impair neuronal function to produce
      symptoms such as memory loss by a means other than plaque formation.

PMID- 8146664
TI  - [Effects of hyperoxia and hypoxia on cerebral circulation and intracranial
      pressure].
AB  - Oxygen is an active stimulus of cerebral blood vessels. Hyperoxia can induce
      decrease in cerebral blood flow and intracranial pressure, but hypoxia increases
      cerebral blood flow and intracranial pressure. Both hyperoxia and hypoxia play an
      opposite role in cerebral circulation and intracranial pressure. Recent studies
      of cerebral circulation and intracranial pressure under hyperoxia and hypoxia
      were reviewed in the present paper with special reference to the correlation
      between cerebral circulation and intracranial pressure.

PMID- 8146665
TI  - [Role of central vasopressin in the maintenance of cardiovascular activities
      during acute hypoxia].
AB  - To investigate whether central vasopressin play a role in the maintenance of
      cardiovascular activities of rats exposed to acute hypoxia, blood pressure, heart
      rate, pressures of left and right ventricles and their dp/dt were monitored in
      rats anesthetized with urethane. The rats were divided into three groups, each of
      which received intracerebroventricular injection (icv.) of V1- and V2
      vasopressinergic antagonists (4 micrograms, each) and equivolumetric vehicle (8
      microliters, served as control group). Ten min after icv. three groups of rats
      were exposed to acute hypoxia (9% O2 in N2) for 15 min before reoxygenation.
      During hypoxia, MBP, HR, LVSP and LV + dp/dtmax of V1-antagonist treated group
      decreased more significantly than those of the control group (P < 0.01). After
      reoxygenation there were no significant differences between both groups. V1
      antagonist and the vehicle had no detectable effect on the cardiovascular
      parameters during normoxia. Although icv. V2-antagonist caused a transient
      augmentations of HR, MBP, LVSP and LV + dp/dtmax except for RVSP and RV +
      dp/dtmax, there were no significant differences in cardiovascular activities
      between V2-antagonist treated group and control group during hypoxia and
      reoxygenation. These results indicate that central endogenous vasopressin play an
      important role in the maintenance of cardiovascular activities during hypoxia via
      its V1-receptor without involving V2-receptor. The central vasopressin does not
      have a tonic effect on cardiovascular activities under normal conditions.

PMID- 8146666
TI  - [Hemodynamic actions of N-nitro-L-arginine and its effect on renal sympathetic
      nerve activity in anesthetized rats].
AB  - The hemodynamic actions of N-nitro-L-arginine (L-NNA), a novel NO synthesis
      inhibitor, and its effect on renal sympathetic nerve activity (RSNA) were
      examined in anesthetized rats to define the possible role of L-NNA in the
      regulation of blood pressure and the underlying mechanism(s). The results
      obtained were as follows. (1) Following intravenous bolus injection of L-NNA (15
      mg/kg), MAP was changed from 9.87 +/- 0.80 to 14.67 +/- 0.53 kPa (P < 0.001), HR
      from 317 +/- 13 to 303 +/- 14 bpm, CI from 9.79 +/- 0.83 to 7.04 +/- 0.41
      ml/min.100 g-1 (P < 0.05), and TPRI from 1.04 +/- 0.10 to 2.15 +/- 0.18 u/100 g
      (P < 0.001), all lasting for more than 30 min. The above-mentioned actions of L
      NNA could be inhibited by prior administration of L-arginine (200 mg/kg). (2) In
      rats with sinoaortic denervation (SAD), i.v. L-NNA might induce an increase in
      HR, indicating that L-NNA-induced bradycardia was resulted from a baroreceptive
      activation. (3) In rats with buffer nerves intact, i.v. L-NNA failed to induce a
      significant change in RSNA, though an increase in MAP accompanied by bradycardia
      was observed. (4) With i.v. L-NNA for SAD rats, MAP, HR and RSNA were markedly
      increased by 55.6%, 5.1% and 34.3%, respectively. The results implied that L-NNA
      was able to activate sympathetic center, and L-NNA-induced change of RSNA could
      be masked by baroreflex. Prior administration of L-arg was capable of inhibiting
      the effect of L-NNA on RSNA in SAD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146667
TI  - [The phase-dependent response of the heart to vagal stimulation in soft-shelled
      turtles].
AB  - Using cardiac cycle length (A-A interval) as an index, the effect of phase
      coupled burst of vagal stimulation on the heart rate were investigated in 27
      turtles. The negative chronotropic response depended on timing of the stimulus
      burst within the cardiac cycle. At first, the A-A interval was lengthened
      progressively and then showed a rapid decrease. The amplitude (AT) of the mean
      phase-response curve to right vagal stimulus in turtles treated by propranolol at
      normal temperature was 1484.10 +/- 213.10 ms. The minimum-to-maximum phase
      difference of the response curves was 804.00 +/- 210.90 ms. Both the AT and (St
      A)max of the response curve varied directly with AA. In contrast, (St-A)min was
      not influenced by AA. Moreover, it was also found that the tau FR, AT, AA and (St
      A)min in hibernant animals were all higher than those in normal ones. However, in
      three of the six hibernant turtles maximum positive chronotropic response could
      be elicited at the time when (A-A)min was elicited by vagal stimulation. The
      results indicated that the phase-dependent response to right vagus in turtles was
      similar to that in homothermal animals, but significantly different both in the
      amplitude of the phase-response and the latency of negative chronotropic
      response. Since the phase-response was abolished by atropine, not by propranolol,
      it was suggested that the occurrence of phase-response was due to changes of
      responsiveness of automatic cells to ACh released from the vagus nerve.

PMID- 8146668
TI  - [Inhibitory effect of diazepam or flurazepam on pressor response induced by the
      stimulation of midbrain in the rabbit].
AB  - Experiments were performed on 32 rabbits anaesthetized with alpha-chloralose and
      urethane, paralyzed with flaxidil and artificially ventilated. The pressor
      response was elicited by stimulation of dorsal part of midbrain periaqueductal
      gray (dPAG). Intravenous injection of diazepam (2 mg/kg) or
      intracerebroventricular application of flurazepam (2 mg/50 microliters) resulted
      in attenuation of the pressor response induced by the stimulation of midbrain.
      Bilateral microinjection of flurazepam (100 micrograms in 0.25 microliter) into
      rostral ventrolateral medulla (rVLM) depressed the pressor response to midbrain
      stimulation. Microinjection of flurazepam of the same dosage into caudal
      ventrolateral medulla (cVLM), however, had no depressant effect. Pretreatment
      with bicuculline in rVLM prevented the inhibitory effect of flurazepam on the
      pressor response. These results mentioned above suggest that diazepam or
      flurazepam inhibits the pressor response evoked by midbrain stimulation, and the
      effect may be mediated by the activation of the GABAA receptor in rVLM.

PMID- 8146669
TI  - [Type and content of adrenoceptors in toad heart].
AB  - The type and content of adrenoceptors in heart of normothermic and cold
      acclimatized toad were studied by radioligand binding assay at different testing
      temperatures. The Bmax and Kd values of membrane from normal toad heart binding
      to 3H-DHA at 37 degrees C were respectively 55.11 +/- 6.22 fmol/mg protein and
      2.15 +/- 0.42 nmol/L for the whole heart, 55.80 +/- 7.03 and 2.65 +/- 0.37 for
      sino-atrium and 54.27 +/- 3.06 and 1.84 +/- 0.14 for ventricle. While the binding
      to 3H-DHE was very low and nonspecific. When membrane from cold-acclimatized toad
      at 5-8 degrees C for 10 days was examined for its binding to 3H-DHA or 3H-DHE at
      10 degrees C, the values of Bmax and Kd were as same as those of normothermic
      toad examined at 37 degrees C. The present results suggest that the toad heart is
      lacking of alpha-adrenoceptor, and the type and content of adrenoceptors are not
      influenced by temperature.

PMID- 8146670
TI  - [Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in amygdala
      of the rat].
AB  - CCK-8 administered bilaterally to the amygdala at 0.1-1.0 ng dose-dependently
      antagonized the analgesia induced by morphine (4 mg/kg, s. c.) as measured by the
      changes in tail flick latency (TFL). This effect of CCK-8 could be reversed by
      Devazepide, a CCK-A receptor antagonist dose-dependently at 50 ng and 200 ng, and
      by L-365, 260, a CCK-B receptor antagonist at 5 ng and 8 ng administered to the
      same site. The effect of morphine analgesia was potentiated by 200 ng Devazepide
      or 8 ng L-365, 260 administered bilaterally to amygdala. Devazepide and L-365,
      260 per second showed no significant influence on basal TFL. The results indicate
      that amygdala is a strategic site where CCK-8 exerts an antiopioid activity.
      Since the effect of L-365, 260 was 25 times more potent than Devazepide, it
      suggests that the anti-opiod effect of CCK in amygdala is mediated by CCK-B
      receptors.

PMID- 8146671
TI  - [Effects of bromocriptine microinjection into VTA on the DOPAC level in nucleus
      accumbens].
AB  - The experiment was performed in sodium pentobarbital anesthetized male SD rats.
      In vivo differential pulse voltammetry (DPV) was used to monitor a metabolite of
      dopamine-3,4-dihydroxyphenylacetic acid (DOPAC) level in the ipsilateral nucleus
      accumbens following microinjection of bromocriptine (2.5 micrograms/0.5
      microliters, n = 5) into left ventral tegmental area (VTA). The results indicated
      that after microinjection the amplitude of DOPAC peak increased gradually and
      reached to 128% and 143% compared to the control at the 50th and 80th min
      respectively (P < 0.01). The duration of the effect was about two hours. One
      hundred and eighty min after injection, the amplitude of DOPAC decreased to 111%
      of control (P > 0.05). SCH23390 (2 nmol/0.5 microliters, n = 4), a selective D1
      antagonist was given into left VTA 40 min prior to microinjection of
      bromocriptine. In this group, the above-mentioned effect of bromocriptine was
      blocked, the amplitude of DOPAC peak showed no increase. The results suggest that
      the microinjection of bromocriptine into VTA induces an increase of activity of
      mesolimbic dopaminergic neurons probably mediated by D1 receptor.

PMID- 8146672
TI  - [Quantitative studies on discrimination of simple geometric patterns and related
      visual illusions].
AB  - Using quantitative psychophysical measurements, the abilities in discriminating
      some simple geometric patterns and the related visual illusions (Zoellner, Muller
      Lyer, Ponzo and Delboeuf illusions) were investigated under luminance contrast
      (LC) and isoluminance color contrast (ICC). The results showed that the subjects
      possessed identical abilities in discriminating parallelity, length and area, and
      illusory distortion perceived for these geometric properties were of the same
      strength, no matter the figures were displayed by LC or ICC. The contour- and
      border illusions, however, vanished at ICC. The minimum contrast inducing contour
      and border illusions (1.8% and 5.3%, respectively) was considerably lower than
      that inducing parallelity illusion (15%). These imply that simple geometric
      properties and contours (or borders) of visual images may be separately
      transmitted by different visual pathways.

PMID- 8146673
TI  - [A study of regenerating liver protects against carbon tetrachloride injury in
      rat].
AB  - In our previous study we had demonstrated that regenerating liver of rats had an
      ability to resist CCl4 injury. In this paper, the underlying mechanism was
      further investigated. Hepatic stimulator substance from regenerating liver (rHSS)
      at different time after partial (68%) hepatectomy was extracted and assayed for
      its biological activity by using 3H-thymidine. The activity is approximately
      seven-fold as compared with the control. Then, rHSS was given to rats to observe
      its effect against CCl4 injury both in vivo and in vitro. The results were as
      follows: rHSS decreases the mortality of CCl4 intoxicated rats and suppresses the
      elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) induced by CCl4 in vivo. Also rHSS increases the cell viability and
      decreases the leakage of intracellular ALT of hepatocytes poisoning by CCl4. The
      above mentioned results suggest rHSS is an important mechanism for regenerating
      liver to protect against CCl4 poisoning.

PMID- 8146674
TI  - [Changes of angiotensin II contents in rat plasma, brain, cardiovascular system
      and adrenal during stress].
AB  - The changes of content of angiotensin II (A II) in plasma, anterior hypothalamus,
      medulla oblongata, myocardium, vasculature and adrenals during acute and chronic
      stress were studied in rats. Compulsive cold-water swimming and trauma by limb
      breaking were used to set acute stress models while cold environment of 4-8
      degrees C was used to set chronic stress model. The results showed that: (1) The
      A II levels in plasma were significantly increased in all three stress- model
      groups, reaching to 900%, 390% and 134% of the control in the swimming group, the
      limb-broken group and the cold environment group, respectively. It's clear that
      the level of angiotension II in the acute stress groups were much higher than
      those in the chronic stress group. (2) The A II levels of the rat brain,
      myocardium and blood vessel were also increased in the stress animals except the
      limb-broken group. Furthermore, the contents of angiotensin II of the chronic
      stress animals were significantly higher than those of the acute stress animals
      in the brain, myocardium and blood vessels, but not in the adrenals. (3) The
      adrenal A II content was significantly higher than that of the control in all
      stressed animals. (4) The plasma corticosterone was also significantly increased
      over the control level in both the acute and chronic stress groups. These results
      suggest that circulating angiotensin II and tissue angiotensin II may play a role
      during the development of acute and chronic stress, respectively.

PMID- 8146675
TI  - [Prolactin inhibits gonadotropin-induced increase in ovarian plasminogen
      activator activity and ovulation in mouse].
AB  - We have demonstrated in this study that prolactin inhibits hCG-induced ovulation
      in PMSG-primed mice. At 18 h after the hormone treatment the number of ova in the
      oviducts was found to be 31.7 +/- 6.7 (mean +/- SE) in hCG treated group. The
      number was significantly decreased (19.7 +/- 4.9) when 100 micrograms of
      prolactin was injected simultaneously. The same effect of PRL on hCG induced
      ovulation could be also observed at 24 h after the hormone treatment; the values
      reached respectively to 32.3 +/- 10.8 and 20.3 +/- 5.4. Both in vivo and in vitro
      experiments further showed that the inhibition of the gonadotropin-induced
      ovulation by PRL is mediated through decreasing in the ovarian plasminogen
      activator activity.

PMID- 8146676
TI  - [Effect of lithium applied iontophoretically on electrical activities of pain
      related neurons in caudate-putamen nucleus of rat].
AB  - Multi-barrelled micro-electrode has been used to observe further the effect of
      Li+ applied iontophoretically on electrical activities of pain related neurons
      (PRN) of the rat caudate-putamen nucleus (CPN) and its mechanism of action was
      studied at the cellular level. It was found that PRN were homogeneously
      distributed throughout the head of CPN, but pain-excitation neurons (PEN) and
      pain-inhibition neurons (PIN) were heterogeneously distributed. The PIN were
      mainly distributed in the anterior part, while the PEN primarily in the central
      part of the head of CPN. The results may provide a clue to understand the
      complicacy in the pain regulation mechanism undergoing in the head of CPN. Li+
      iontophoresis could inhibit the discharges of PEN, while the discharges of PIN
      were activated. The interference modes of pain discharge of PEN and PIN induced
      by Li+ iontophoresis were positively related to that induced by morphine. It was
      suggested that there existed some similarity in the mechanisms of analgesia
      induced by Li+ and morphine. This, in turn, appears to support the suggestion
      that endogenous opioid peptides and opioid receptors may be involved in the
      analgesic effect of Li+.

PMID- 8146677
TI  - [The effects of opioid peptides on postsynaptic potentials in slice preparation
      of nucleus accumbens of rats].
AB  - Behavioral studies indicate that nucleus accumbens (NAcc) is a key brain area for
      the rewarding effects of opiate and for opiate addiction. To find out the
      cellular correlates of opiate addiction, the effects of three kinds of opiate
      peptides on membrane potential and postsynaptic potentials (PSPs) in a slice
      preparation of NAcc were studies by intracellular recording and current-clamp
      technique. The results indicated that superfusion of opioid 7 peptides did not
      affect membrane potential and input resistance of NAcc neurons, but significantly
      reduced postsynaptic potentials. Naloxone superfusion significantly reversed the
      depressant effects of mu and sigma receptor agonist (DAGO, D-Pen) on PSPs, but
      not on those of kappa agonist (U-50). These results suggest that opioid peptides
      predominantly reduce synaptic transmission in NAcc.

PMID- 8146678
TI  - [Effect of nanhumycin on neuromuscular transmission and its mechanism].
AB  - Nanhumycin (NHM) is a new polyether antibiotic, which suppresses the growth
      Bacillus subtilis and shows an anticoccidial effect. By means of intracellular
      recording technique, the effects of NHM on mouse phrenic nerve-diaphragm
      preparations were observed. The main results are as follows: (1)20 micrograms/ml
      NHM irreversibly blocked neuromuscular transmission in 1.5-2.0 h. (2) 2-20
      micrograms/ml NHM evoked a drastic and spasmodic increase of the frequency of
      miniature endplate potentials (MEPPs) and a simultaneous increase of the mean
      quantal content of endplate potentials for 40-60 min, which was followed by
      complete blockage of EPPs. (3) NHM decreased the resting potential (RP) of muscle
      cells progressively and irreversibly. (4) NHM's effects on RP or MEPP disappeared
      in Na(+)-free physiological solution but persisted in the presence of
      tetrodotoxin (TTX). All these results support the notion that NHM is a cation
      ionophore, Na+ carrier.

PMID- 8146679
TI  - [Effects of luminance contrast and color contrast between components of illusory
      figure on the illusion magnitude].
AB  - Using quantitative psychophysical measurements, the effects of luminance contrast
      (LC) and equiluminance color contrast (ECC) between components of illusory
      figures on the magnitudes of orientation illusion (Zoellner illusion), length
      illusion (Muller-Lyer illusion and Ponzo illusion) and area illusion (Delboeuf
      illusion) were investigated. The results showed that, compared with normal
      illusory magnitude, the illusory magnitude of the subjects decreased obviously
      when LC or ECC existed between the components of the illusory figures. The
      decrease was especially obvious in the orientation illusion. The minimum
      contrasts for inducing contour and border illusions were only 1.8% and 5.3% under
      LC. They increased to 66.0% and 46.4% respectively when both luminance and color
      contrasts were introduced into the figures. These observations provided evidence
      for the existence of mutual inhibition between the luminance, color and form
      channels of the visual system.

PMID- 8146680
TI  - [Relaxation of coronary arterial smooth muscle and depolarization of cell
      membrane potential by selenium].
AB  - Selenium (Se) is an important trace element to the human being. The effects of
      selenium on contraction and cell membrane potential of coronary arterial smooth
      muscle were studied in guinea pig by isometric force development of strips and
      intracellular recording method. It was showed that Se caused vascular smooth
      muscle relaxation and depolarization of the cells in a dose dependent manner.
      Inhibitory effect of Se on KCl- or ACh-induced contraction could be
      quantitatively assessed by a rightward shift of the concentration-response curve.
      Furthermore, Se increased KCl-induced depolarization and decreased ACh-induced
      hyperpolarization.

PMID- 8146681
TI  - [Roles of vagal projection areas afferents on vagal input-evoked depressor
      response].
AB  - Vagal afferents project directly or indirectly to several brain areas. In
      urethane-anesthetized and bilaterally vagotomized rats, either procaine injection
      into the nucleus tractus solitarii (NTS) or beta-endorphin antiserum injection
      into the rostral ventrolateral medulla (RVL) markedly decreased the depressor
      (DpV) and bradycardia response to stimulation of cervical vagal afferents, while
      propranolol (or beta-endorphin antiserum) injection into the nucleus
      paraventricularis and procaine injection into the area postrema had no
      significant effect. In left vagotomized rats, the DpV remained unchanged after
      methyl atropine (i.v), but the bradycardia response during the DpV was
      attenuated. Since our previous study has shown the NTS can induce a depressor
      response via its beta-endorphinergic projections to RVL, the above results
      suggest that the inhibitory effect of vagal afferents on the RVL
      sympathoexcitatory neurons via NTS beta-endorphinergic neurons represents one
      aspect of the mechanism underlying DpV.

PMID- 8146682
TI  - [Stimulatory effect of vasoactive intestinal peptide microinjected into dorsal
      vagal complex on gastric acid secretion in rats].
AB  - Effects of microinjection of vasoactive intestinal peptide (VIP) into cisterna
      magna, dorsal vagal complex (dorsal motor nucleus of the vagus, nucleus tractus
      solitarius and area postrema) and spinal subarachnoid space on gastric acid
      secretion (GAS) were observed in Ghosh-Schild's rats. The results were as
      follows: (1) VIP (10 micrograms) injected into the cisterna magna significantly
      stimulated GAS reaching a peak at 60-100 min after injection and lasting for more
      than 2.5 h. (2) The increase could be completely abolished by bilateral
      subdiaphragmatic vagotomy. (3) 20-30 min after injection of 1 microgram VIP into
      the dorsal vagal complex could also induce a peak increase in GAS. (4)
      Intrathecal injection of VIP (10 micrograms) did not affect GAS. The results
      indicate that central VIP-stimulated GAS is mediated by vagus from a special
      region of dorsal vagal complex.

PMID- 8146683
TI  - [Submaxillary gland epidermal growth factor accelerated healing of chronic
      gastric mucosal lesions in rats].
AB  - Large amount of EGF-like immunoreactivity was observed in the submandibular gland
      of rats with immunohistochemical method. The staining is mainly localized in the
      ductal cells. The level of EGF in gastric juice and serum was measured with a
      specific and sensitive RIA method. It was observed that EGF level was decreased
      both in gastric juice and in serum after sialoadenectomy and subsequent healing
      of chronic gastric ulcer induced by serosal acetic acid was delayed. Oral
      administration of EGF to sialoadenectomized rats could reverse the lowered rate
      of ulcer healing to almost normal level. The above results suggested that
      secretion of EGF may have an important effect on the healing of chronic gastric
      lesions in rats.

PMID- 8146684
TI  - [Mechanism of effect of intraventricular administration of histamine H1-receptor
      agonists on gastric acid secretion in rats].
AB  - The present experiment is undertaken to study the mechanism of the inhibitory
      effect of 2-pyridylethylamine (PEA, i.c.v.) on the gastric acid secretion.
      Gastric acid was continuously washed out with 37 degrees C saline by means of a
      perfusion pump in Wistar rats weighing 200-300 g. Drugs were injected into the
      third ventricle to examine the effect on pentagastrin-induced (160 micrograms/kg,
      s.c.) gastric acid secretion. The results were as follows: (1) Pretreatment with
      naloxone (2.5 micrograms, i.c.v.) blocked the inhibitory effect of PEA (10
      micrograms, i.c.v.) on gastric acid secretion. (2) The inhibitory effect of PEA
      (5-20 micrograms, i.c.v.) was turned into an excitatory effect after
      subdiaphragmatic vagotomy in a dose-dependent manner, but not changed by
      bilateral adrenalectomy. (3) In vagotomized rats, pretreatment with CRF-antiserum
      (1:20,000, 2.5 microliters, i.c.v.) or bilateral adrenalectomy abolished the
      excitatory effect of PEA (10 micrograms, i.c.v.). (4) PEA (10 micrograms, i.c.v.)
      did not change the basal gastric acid secretion in vagotomized rats. These
      results suggest that histamine H1-receptor in brain may be involved in both the
      inhibitory and excitatory regulation of gastric acid secretion mediated by vagus
      nerve and the hypothalamus-pituitary-adrenal axis.

PMID- 8146685
TI  - [The increase in endocytosis of mouse skeletal muscle after denervation and the
      proliferation of satellite cells].
AB  - The relationship between increase of endocytosis and proliferation of satellite
      cells in mouse skeletal muscle was studied by biochemical and culture methods in
      vitro. The results indicated that: (1) 4 d or 6 d after denervation, increase of
      endocytosis and proliferation of satellite cells in denervated muscle were
      induced. (2) Actinomycin D inhibited activation of satellite cells and
      endocytosis in normal muscle. (3) While in denervated muscle, actinomycin D
      inhibited proliferation of satellite cells as well as increase of endocytosis,
      but could not prevent muscle atrophy after denervation. These results imply that
      proliferation of satellite cells and increase of endocytosis in the muscle may
      concur to the appearance of some factors after denervation, or increase in
      endocytosis is a mere result of proliferation of satellite cells.

PMID- 8146686
TI  - [Alpha 1-adrenoceptor involved in the process of VSMp control of renal
      sympathetic nerve activities in spinal cord in rats].
AB  - Experiment were performed on 40 urethane anesthetized Wistar rats. After
      preinjection of 6-hydroxydopamine (6-OHDA) into subarachnoid cavity at inferior
      thoracic part. Enhancement of renal sympathetic nerve activity (RSNA) and mean
      arterial pressure (MAP) induced by electrical stimulation of pressor area of
      ventral surface of medulla (VSMp) were attenuated; but intrathecal phenylephrine
      had no effects. The results suggest that the alpha 1-adrenoceptors mediating
      descending excitatory effects of VSMp are located postsynaptically on the
      sympathetic preganglionic neurons.

PMID- 8146687
TI  - Biosocial models of adolescent problem behavior: extension to panel design.
AB  - We extended the biosocial model of problem behavior tested by Udry (1990) to a
      panel design, following a sample of over one hundred boys in adolescence for
      three years. We found the expected results for sociological variables, but weaker
      effects for testosterone than Udry found on cross-sectional data. Using panel
      models with lagged hormone effects, we identified relationships between Time-1
      testosterone and problem behavior one year or more later. The relationship
      between testosterone and problem behavior was not present for subsequent measures
      of testosterone, either in cross-section or with time-lagged models. Therefore we
      cannot interpret the results as showing testosterone effects on problem behavior.
      Rather it appears that testosterone level in early adolescence is a marker for a
      more general growth trajectory of early development.

PMID- 8146688
TI  - How does variation in fetal loss affect the distribution of waiting times to
      conception?
AB  - Unmeasured variation has long been a concern in analyses of the waiting time to
      conception. Recent work by Heckman and Walker (1991) and Trussell and Rodriguez
      (1990) has underscored the fact that statistical considerations alone cannot
      discriminate among likely models describing the distribution. Here, we specify a
      single theoretically important source of heterogeneity, namely variability in
      intrauterine mortality, and assess its effects on the waiting times to a
      conception which results in a live birth. We find that the effects on the waiting
      times to a conception which results in a live birth. We find that the effects of
      variation in fetal loss are confined to the tail of the distribution. Unless
      variation in fetal loss is extremely large or a substantial proportion of
      observed waiting times are initiated at late ages, variation in fetal loss does
      not appear to explain much variation in conception waits. We conclude that
      heterogeneity in fetal loss does not explain the variation in fecundability that
      has been observed for first birth intervals. This conclusion supports the
      hypothesis that at early ages (below age 35) variation in the waiting time to a
      fertile conception may largely reflect the proportion of nonsusceptible couples
      in the population. The analyses suggest that for the purposes of testing
      theoretically motivated models, future efforts should be directed toward
      examining reproductive experience after age 35 and toward incorporating
      information on characteristics of the fertile period as it becomes known.

PMID- 8146689
TI  - An evaluation of survey data on birthweight and prematurity status.
AB  - The 1986 experimental Demographic and Health Survey in the Dominican Republic was
      one of the first retrospective, population-based surveys of a developing country
      to collect information on prematurity status as well as birthweight. We show that
      the relationships among birthweight, prematurity status, and infant mortality are
      consistent with corresponding patterns observed in other Latin American and
      Caribbean countries and in developed nations. Two notable irregularities in the
      birthweight data are the atypically high proportion of infants weighing 4,000
      grams or more, and the high mortality rates among infants with missing
      birthweight. Problems with the prematurity status data include an unexpectedly
      low proportion of premature births, an unusually small proportion of low
      birthweight explained by premature births, and an extremely high neonatal death
      rate among premature compared to term infants. Inclusion of an explicit
      definition of "premature" may help avert similar problems in future health
      surveys.

PMID- 8146690
TI  - Specific neuro-cognitive impairments associated with Turner (45,X) and
      Klinefelter (47,XXY) syndromes: a review.
AB  - In Turner syndrome, there is a high incidence of neuro-cognitive impairment
      specific to the mental processing and sequencing of rotational transformations of
      shapes in the spatial dimensions of left-right, up-down, and back-front. In
      Klinefelter syndrome, the corresponding neuro-cognitive impairment is specific to
      the mental processing of sequence and synchrony in the temporal dimension,
      including the temporal dimension of language.

PMID- 8146692
TI  - Sociocultural factors and the genetic diversification of Amazonian Indians: a
      brief overview.

PMID- 8146691
TI  - How pervasive are sex differentials in childhood nutritional levels in south
      Asia?
AB  - This paper considers the assumption that there are widespread sex differentials
      in the household allocation of food in South Asia. From primary field data and a
      critical review of the existing literature, it concludes that we have no reason
      to believe that girls in this region invariably get an unfair deal in the matter
      of nutrition, even in those areas where sex differentials in child mortality are
      the most acute. Too much of the research to support such a contention starts with
      the biased view that gender differences in nutritional status must exist. It is
      pointed out in this paper that a new look at this issue is essential if we are to
      use scarce resources most effectively to fight gender inequalities. By
      identifying more precisely the areas in which women are worst discriminated
      against, action to affect these areas can be focused much better than by
      spreading efforts into programs where the need is at best marginal.

PMID- 8146693
TI  - Marital assortment and phenotypic convergence: longitudinal evidence.
AB  - This study provides a direct test of whether the observed similarity of spouses
      is due to initial assortment rather than to convergence of phenotypes. With data
      from three well-known longitudinal studies, phenotypic convergence is examined
      using both variable- and person-centered analyses. The longitudinal evidence does
      not support the hypothesis that couples increasingly resemble each other with
      time. Spouse correlations most likely reflect initial assortment at marriage and
      not the convergence of phenotypes.

PMID- 8146694
TI  - Sex-linked strategies of human reproductive behavior.
AB  - We present data on fertility characteristics in the Venezuelan population for
      each sex separately, allowing a detailed comparative analysis of the variance in
      fertility between males and females. We show that the fertility distribution for
      both sexes is discontinuous, that the average female has a larger number of
      offspring per individual than the average male, and that highly fertile males
      outnumber highly fertile females so that the total number of offspring produced
      by males and females is balanced. Results indicate that a few males are
      responsible for a relative higher fertility of the average female and that
      interactions between polyandric females with monogamic and polygynic males are
      common. Among the Yanomami, a relatively unacculturated hunter-gatherer
      horticulturist tribe, similar differences in fertility distribution of both sexes
      are apparent. The data suggest that human populations contain statistically
      distinct subpopulations, with different reproductive strategies, suggesting the
      existence of complex interactions among human populations which are not evident
      from the study of individuals or groups.

PMID- 8146695
TI  - Breastfeeding and postpartum amenorrhea in a traditional society: a hazards model
      analysis.
AB  - There is considerable variation in the length of the postpartum amenorrhea during
      which breastfeeding suppresses fertility, both within and between societies. In
      this paper, we investigate the association between breastfeeding and the
      resumption of menses and the impact of various biological and social covariates
      thereon, using data from two retrospective surveys in India. We use both
      univariate life table and multivariate time-dependent hazards techniques to
      analyze the data. Most prior investigations related the impact of breastfeeding
      to postpartum amenorrhea by taking duration of breastfeeding as a fixed
      covariate. However, breastfeeding beyond the resumption of menstruation cannot
      affect the duration of menses. Accordingly, the present study has a
      methodological focus in the sense that breastfeeding is treated as a time
      dependent covariate. We found that breastfeeding, age of mother at child's birth,
      social status, level of income, religion and caste (subcaste), and residential
      status have significant effects on return of menses in Indian traditional
      society.

PMID- 8146696
TI  - Relationships between aggression and pubertal increases in testosterone: a panel
      analysis of adolescent males.
AB  - Existing data linking testosterone (T) and aggression in human adult males are
      surprisingly tenuous. In one of the few studies based on adolescent males, Olweus
      et al. (1988) demonstrated strong relationships between concurrent measures of T
      and aggression. However, the conclusions that could be drawn regarding
      developmental change were limited. Using data from a three-year panel study of
      100 adolescent males (ages 12 to 13 at study entry), we examined whether there
      are significant relationships between concurrently collected measures of T and
      self-ratings of aggression, and whether the dramatic pubertal rise in T predicts
      subsequent change in aggression ratings. Panel analyses incorporating concurrent,
      lagged, and change measures found few significant relationships between
      aggression and T or pubertal development. The general absence of T/aggression
      relationships is discussed in the context of other empirical findings, the
      aggression measures used, and prepubertal differentiation on aggression.

PMID- 8146697
TI  - Hindu and Christian fertility in India: a test of three hypotheses.
AB  - Three hypotheses interpret differences in human fertility among religious groups.
      The Particularistic Theology Hypothesis stresses the pronatalist influence of
      doctrines forbidding artificial contraception and emphasizing the importance of
      sons, while the Characteristics Hypothesis focuses on the antinatalist effect of
      urban residence, higher education, and late age at marriage. But the Minority
      Status Hypothesis argues that such antinatalist effects may be stronger for a
      minority than a majority, since better-educated, late-marrying urbanites have
      greater chances for upward mobility. Minority groups with these advantages may
      have much lower fertility than similar people in the majority group if
      antinatalism is seen as a way to counter prejudice and move up. I tested these
      three hypotheses with data from the 1981 Census of India, from which I calculated
      mean numbers of children ever born per wife aged 35-44. I standardized the mean
      for differences between Hindu and Christian women by urban residence, education,
      age, and length of marriage. The standardized fertility rates of Hindus and
      Christians were similar in 25 states/union territories. Only in Meghalaya,
      Mizoram, and Nagaland did the Hindu religious minority have a lower standardized
      birth rate than the Christian majority; but the Muslim minority had one like the
      Christians'. This pattern was most consistent with the Characteristics
      Hypothesis.

PMID- 8146698
TI  - Efficiency and equity of health care systems.

PMID- 8146699
TI  - The disablement process.
AB  - Building on prior conceptual schemes, this article presents a sociomedical model
      of disability, called The Disablement Process, that is especially useful for
      epidemiological and clinical research. The Disablement Process: (1) describes how
      chronic and acute conditions affect functioning in specific body systems, generic
      physical and mental actions, and activities of daily life, and (2) describes the
      personal and environmental factors that speed or slow disablement, namely, risk
      factors, interventions, and exacerbators. A main pathway that links Pathology,
      Impairments, Functional Limitations, and Disability is explicated. Disability is
      defined as difficulty doing activities in any domain of life (from hygiene to
      hobbies, errands to sleep) due to a health or physical problem. Feedback effects
      are included in the model to cover dysfunction spirals (pernicious loops of
      dysfunction) and secondary conditions (new pathology launched by a given
      disablement process). We distinguish intrinsic disability (without personal or
      equipment assistance) and actual disability (with such assistance), noting the
      scientific and political importance of measuring both. Disability is not a
      personal characteristic, but is instead a gap between personal capability and
      environmental demand. Survey researchers and clinicians tend to focus on personal
      capability, overlooking the efforts people commonly make to reduce demand by
      activity accommodations, environmental modifications, psychological coping, and
      external supports. We compare the disablement experiences of people who acquire
      chronic conditions early in life (lifelong disability) and those who acquire them
      in mid or late life (late-life disability). The Disablement Process can help
      inform research (the epidemiology of disability) and public health (prevention of
      disability) activities.

PMID- 8146700
TI  - Making a killing south of the border: transnational cigarette companies in Mexico
      and Guatemala.
AB  - Cigarette smoking is the most unnecessary of modern epidemics in the world today,
      according to the World Health Organization. In response to declining sales at
      home, multinational cigarette companies are increasingly targeting allegedly
      developing countries with their deadly products, often with the strong support of
      the U.S. government. While Asian countries have been most heavily targeted in
      recent years, Latin American countries have not been overlooked. This paper
      discusses macro-level and micro-level implications of the tobacco companies'
      promotions, based on data gathered in Mexico and Guatemala during 1990.
      Recommendations for combating the corporations' efforts are also discussed.

PMID- 8146701
TI  - A follow-up of second generation Afro-Caribbeans and white British with a first
      admission diagnosis of schizophrenia: attitudes to mental illness and psychiatric
      services of patients and relatives.
AB  - A sample of second generation Afro-Caribbeans and white British with a diagnosis
      of schizophrenia, and their relatives, were interviewed 5-10 years after first
      admission. There was no difference between Afro-Caribbeans and whites on measures
      of satisfaction, conceptualization about illness and attitudes to different types
      of treatment and management. However black relatives were more likely to
      attribute causation of illness to substance use and to view services as racist.
      Most black patients and relatives thought that black day centres would be
      beneficial.

PMID- 8146702
TI  - Socio-geographical patterns of HIV-1 transmission in Kagera Region, Tanzania.
AB  - A population-based study on the prevalence of HIV-1 infection in the Kagera
      region was performed in 1987. The study was based on a multistage cluster
      sampling technique covering the age-group 15-54 years. The study showed
      considerable variation of prevalence of HIV-1 infection in the areas studied. A
      total of 2475 adults were studied and the overall prevalence of HIV-1 infection
      in the region was 9.6% with a higher prevalence in the urban area (24.2%)
      compared to that in the rural areas (4.9%). In the present analysis, information
      on individuals collected during the prevalence study has been used to
      characterize smaller geographical areas of several villages (wards) and to form
      the basis for an aggregated analysis of geographical and social patterns relevant
      to HIV-1 transmission in the studied areas of the region. Kagera region is a
      heterogeneous society with respect to, for example, religion, ethnic groups and
      family patterns. There was a moderately strong positive correlation between HIV-1
      prevalence and frequent change of sexual partners on the ward level. In Bukoba
      town the prevalence varied remarkably among the wards, with the lowest prevalence
      in the ward having the highest social status. In the rural areas, however, the
      prevalence in the wards decreased considerably with increasing distance from
      Bukoba town. This aggregated analysis of socio-geographical patterns of HIV-1
      transmission characteristics has provided us with information for prioritizing
      areas of HIV/AIDS intervention in the Kagera community.

PMID- 8146703
TI  - Knowledge and meaning: the AIDS education campaign in rural northeast Thailand.
AB  - Nearly 80% of Thailand's population live in the rural sector. To date, these
      villages have been subject to top-down dissemination of HIV/AIDS education
      information via the mass media and bureaucratic networks. This report details an
      ethnographic enquiry into the impact education campaigns are having in one
      village in Northeast Thailand. It is found that AIDS information is primarily
      integrated with local conceptions of sexual behaviour and commercial sex. By the
      early 1990s, heterosexual behaviour is a major mode of HIV transmission in
      Thailand. Local and international media discourse focuses on the commercial sex
      industry in describing the spread of the virus. However, the lack of detailed
      research of sexual practices in Thailand makes accurate projections of HIV
      transmission difficult and allows unsubstantiated claims to be made concerning
      typical Thai sexual behaviour. This paper explores the local context in which
      these practices are found and discusses the meanings villages attached to
      HIV/AIDS information. Knowledge levels and behaviour change are assessed and it
      is argued that community based imperatives are essential for effective future
      campaigning.

PMID- 8146704
TI  - Change of occupation and retirement among Swedish farmers and farm workers in
      relation to those in other occupations. A study of "elimination" from farming
      during the period 1970-1988.
AB  - A number of studies carried out in different countries have shown that farmers
      have a low morbidity and mortality in comparison to those in other occupations.
      However, this has been questioned on the basis that some type of selective
      process may be operating, in that persons having health problems will avoid
      farming, or are forced to leave farming for other occupations. To determine the
      occurrence of a so-called 'healthy worker effect', this postal survey of
      'elimination' from farming and farming-associated occupations has been carried
      out. A total of 1283 male farmers and 334 male farm workers born in 1935 and
      active in Sweden in 1970 were taken as the study group. As controls, a similar
      number of occupationally active men of the same age and living in the same
      municipalities were randomly chosen. The results showed that farmers changed
      occupation or retired early less often than those in other occupations did,
      whereas more farm workers changed occupation and retired than did other workers
      of the same age. Among the different reasons given for work change/retirement,
      low income/poor earning capacity was more common among the farmers and farm
      workers than among the controls. Illness was less common among farmers but tended
      to be more common among farm workers as cause of work change. Few farmers changed
      their occupation because they were offered other work, in comparison to those in
      other occupations. Allergic disease more often led to an occupation change among
      farmers, while they less often gave cardiac disease and locomotor problems as a
      reason for change of occupation, this was probably also true for the farm
      workers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146705
TI  - Disability, stigma and deviance.
AB  - An important contribution social science research makes to understanding the
      experiences of disabled individuals in the U.S. is to illuminate the influence of
      stigma and deviance on those experiences. Because perceptions of negative
      difference (deviance) and their evocation of adverse responses (stigma) have been
      and continue to be widespread, it is these with which alternate perceptions and
      responses vie in the construction of disability's symbolic and practical
      meanings. While some research demonstrates a regrettable imposition of
      stigma/deviance into the lives and minds of disabled people, some of it shows
      disabled people resisting stigma/deviance imputations; and some of it suggests
      that such imputations are losing force as new ways of thinking about the meaning
      of disability gain sway.

PMID- 8146706
TI  - Reliability of the Spanish version of the Nottingham Health Profile in patients
      with stable end-stage renal disease.
AB  - OBJECTIVE: Since reproducibility of results is a basic prerequisite of health
      status measures for its use in prospective and evaluative studies, the
      reliability of the Spanish version of the Nottingham Health Profile (NHP), a
      multi-dimensional perceived health status measure, was assessed in a sample of
      stable end-stage renal disease (ESRD) patients. METHODS: The NHP was administered
      on two occasions four weeks apart to a group of hospital hemodialysis program
      patients who were clinically stable according to their physicians. Correlations
      of scores and agreement of first and second administrations were assessed
      together with internal consistency. Afterwards, analyses were repeated taking
      into account the time (before, during or after the dialysis) and the method of
      administration (self vs interviewer), and the interviewer. RESULTS: Spearman
      correlation coefficients (rs) between responses to the first and to the second
      administration were > 0.6 for all of the six dimensions of the NHP (range = 0.69
      0.85) and in every sub-group analyzed (P < 0.01). Agreement percent (AP) between
      items was > 0.4 (0.48-0.65). Internal consistency was 0.91 for the whole profile
      and > 0.5 (0.58-0.86) when analyzed by individual dimensions. Reliability did not
      vary significantly with the time nor the method of administration (self or
      interviewer). CONCLUSIONS: Overall, results suggest that the Spanish version of
      NHP is sufficiently reliable to be used in ESRD patients. While a higher
      reliability would have been achieved by a shorter retest period, the study
      provides a realistic approximation to the reliability of the questionnaire in
      actual research and clinical applications.

PMID- 8146707
TI  - Quality of life and maladjustment associated with hair loss in women with
      alopecia androgenetica.
AB  - Quality of life and maladjustment related to hair loss were studied by means of a
      standardized interview in a group of 58 women with alopecia androgenetica who
      applied for treatment at the Department of Dermatology. The hair loss was found
      to have a negative influence on the quality of life on the majority of them. In
      88%, hair loss had negative effects on their daily life; in about 75%, the hair
      problems were manifested in negative self-esteem and about 50% experienced social
      problems. General psychosocial maladjustment in relation to hair loss was
      indicated in almost one-third of the women.

PMID- 8146708
TI  - A study of the relationship of rice cultivation and annual parasite incidence of
      malaria in India.
AB  - Twenty one year data (1963-1983) of 25 states/UTs of India on area under rice
      cultivation and annual parasite incidence was analysed using correlation and
      regression analysis to evaluate the relationship of irrigated area under rice
      cultivation and the statewise annual parasite incidence of malaria. In 23 states
      either the correlation is negative or non-significant whereas in Punjab and
      Nagaland significant positive correlation is observed. Study showed that in India
      at the macro level (i.e. data pooled at the state level both for rice cultivation
      and (API) rice cultivation by and large had poor relationship to API.

PMID- 8146709
TI  - Growth models and the HIV epidemic in Finland.
AB  - Today, we know a lot about HIV and AIDS, yet too little to be able to stop the
      pandemic by a vaccination or by medication. Until that day is at hand, the only
      means of controlling the pandemic is by information--information about the
      diffusion of the virus, about risk behaviour, about safe sex, and about social
      responsibility. Educating people must be based on concise clinical experience, an
      up-to-date picture of the epidemiological situation, and reliable forecasts about
      the future course of the epidemic. Producing reliable forecasts about the HIV
      epidemic has proved to be a more complicated task than expected. The proven,
      reliable, and in most cases very useful epidemiological models have been far from
      successful when applied to the HIV epidemic. The reason for this is mostly due to
      the lack of reliable data depicting the true HIV seroprevalence. Instead of being
      handicapped by the problems of inadequate data, geographical modelling of the HIV
      epidemic is able to rely on its theoretical understanding and good knowledge
      about the spatial organization and the functioning of societies to make is
      forecasts. Due to its flexibility of approach, geographical modelling can adjust
      itself to less accurate data, thus providing an interim forecasting instrument
      until epidemiological modelling becomes successful. This paper presents the
      results of an analysis of the HIV epidemic in Finland based on cartographic
      analysis of municipal data and the use of a simple growth model.

PMID- 8146710
TI  - Depression and the development of cancer: a meta-analysis.
AB  - There is considerable support among members of the public and health
      professionals for the view that depression is an aetiological factor in the
      development of cancer. We review evidence for this hypothesis based upon
      prospective longitudinal studies measuring depression at time 1 and subsequent
      incidence of cancer over the intervening period to time 2. A meta-analysis of
      available studies indicates a small, but marginally statistically significant
      association between depression and the later development of cancer. However, the
      practical significance of this association for the prevention of cancer is
      negligible.

PMID- 8146711
TI  - Height and the risk of acute myocardial infarction in Italian women.
AB  - The relationship between body height and risk of acute myocardial infarction
      (AMI) was investigated in a case-control study conducted in Northern Italy on 429
      women with AMI under age 75 and 863 controls in hospital for acute conditions,
      unrelated to known or potential risk factors for coronary heart disease. Compared
      to women in the highest tertile of height, the relative risks (RR) adjusted for
      age were 1.1 (95% confidence interval, CI, 0.9-1.5) for the intermediate tertile,
      and 1.3 (95% Cl 1.0-1.8) for the lowest tertile. The trend in risk was
      significant (chi 1(2) = 3.89, P = 0.05). Adjustment for several potential
      confounding variables, including age, body mass index, education, smoking habits,
      family history of AMI, history of diabetes, hypertension and hyperlipidaemia did
      not materially modify these estimates: the RR for the highest vs the lowest
      tertile was 1.4 (95% CI 1.0-1.0). The association was stronger in elderly women,
      i.e. in earlier generations, and in heavier ones. This positive association is
      discussed in terms of socio-economic conditions, since low stature may be related
      to poor living conditions and unfavourable environmental factors in childhood and
      adolescence among earlier generations of Italian women.

PMID- 8146712
TI  - Perception of risks and benefits of in vitro fertilization, genetic engineering
      and biotechnology.
AB  - The use of new biotechnology in medicine has become an everyday experience, but
      many people still express concern about biotechnology. Concerns are evoked
      particularly by the phrases genetic engineering and in vitro fertilization (IVF),
      and these concerns persist despite more than a decade of their use in medicine.
      Mailed nationwide opinion surveys on attitudes to biotechnology were conducted in
      Japan, among samples of the public (N = 551), high school biology teachers (N =
      228), scientists (N = 555) and nurses (N = 301). People do see more benefits
      coming from science than harm when balanced against the risks. There were
      especially mixed perceptions of benefit and risk about IVF and genetic
      engineering, and a relatively high degree of worry compared to other developments
      of science and technology. A discussion of assisted reproductive technologies and
      surrogacy in Japan is also made. The opinions of people in Japan were compared to
      the results of previous surveys conducted in Japan, and international surveys
      conducted in Australia, China, Europe, New Zealand, U.K. and U.S.A. Japanese have
      a very high awareness of biotechnology, 97% saying that they had heard of the
      word. They also have a high level of awareness of IVF and genetic engineering.
      Genetic engineering was said to be a worthwhile research area for Japan by 76%,
      while 58% perceived research on IVF as being worthwhile, however 61% were worried
      about research on IVF or genetic engineering. Japanese expressed more concern
      about IVF and genetic engineering than New Zealanders. The major reason cited for
      rejection of genetic manipulation research in Japan and New Zealand was that it
      was seen as interfering with nature, playing God or as unethical. The emotions
      concerning these technologies are complex, and we should avoid using simplistic
      public opinion data as measures of public perceptions. The level of concern
      expressed by scientists and teachers in Japan suggest that public education
      "technology promotion campaigns" will not reduce concern about science and
      technology. Such concern should be valued as discretion that is basic to
      increasing the bioethical maturity of a society, rather than being feared.

PMID- 8146713
TI  - Government participation in physician negotiations in German economic policy as
      applied to universal health care coverage in the United States.
AB  - Systems of universal health care coverage in western industrial societies have
      usually established some form of government participation in negotiations over
      physician payment as a means of controlling costs. In the Federal Republic of
      Germany, a mixed private and public body. Concerted Action in Health Care sets a
      'target' for physician and 'sickness fund' negotiators. This indirect form of
      government participation is effective in 'linking' fees with utilization during
      negotiations, avoiding inflationary trends inherent in fee-for-service systems.
      This target-setting factor is a necessary complement to negotiation of a 'pool'
      of money, wage level and technological adjustment factors, as contained in a
      model of German economic health care policy. These four elements of economic
      policy are recommended as cost control measures for office-based physician
      payments under conditions of universal health care coverage in the United States.
      Indirect government participation through setting 'targets' for negotiations is
      seen as consistent with established American institutional practices.

PMID- 8146714
TI  - Quality judgements by patients on general practice care: a literature analysis.
AB  - Patient report seems to be a workable method for quality assurance. For the
      purpose of the development of such a method, a review was made of 40 studies into
      patient judgements on general practice care. Apparently, many aspects of care are
      only rarely included in patient report and the patients themselves are hardly
      ever involved in selecting these aspects. Furthermore, there appears to be a
      large variety in the methods that are used. The conclusion must be that in the
      field of general practice care only little progress has been made in the
      development of patient report as a method for quality assurance.

PMID- 8146715
TI  - Equity in authorship: a strategy for assigning credit when publishing.
AB  - Existing guidelines for authorship are lacking in specific detail, differ from
      discipline to discipline, implicitly or explicitly contradict each other on many
      issues, and are therefore open to varying interpretation by different people. In
      order to encourage and facilitate consistency and fair acknowledgement of
      contributions to publications, a Points System was developed for evaluating 13
      categories of contribution by individuals. The system is intended for use in
      determining who should be listed as authors, and in what sequence names should
      appear by enabling points "earned" through contribution to be then "spent" in
      purchasing authorship. The system is based on ratings of perceived values of the
      contribution types obtained from the staff of a multi-disciplinary research
      centre, but it can readily be adapted to the local needs and values of any
      research group. The system is likely to be particularly useful in relation to
      complex research projects and programs, to which a number of individuals from
      different disciplines make contributions over time, and/or from which several
      publications are derived.

PMID- 8146716
TI  - Explanatory models of diabetes: patient practitioner variation.
AB  - Most cases of diabetes, a complex disorder that requires many lifestyle changes,
      can be controlled if persons adhere to their prescribed regimen. However,
      compliance is difficult to attain. Differences in explanatory models between
      client and practitioner have been suggested as one reason for non-compliance in
      several disorders. In this ethnographic investigation, individual explanatory
      models were elicited from persons with diabetes and from health professionals
      working with these patients. Professionals described models of diabetes in
      general and their model of a particular patient's diabetes. A composite
      professional model was constructed and compared with each of the patients'
      models. The models were most congruent regarding treatment. Etiology,
      pathophysiology, and severity had less congruence, and time and mode of symptom
      onset were least congruent. The Spearman correlation coefficient showed a
      positive but non-significant association of explanatory model congruence between
      professionals and patients with normal glycosylated hemoglobin levels. Patients
      and professionals seem to emphasize different domains; patients emphasized
      difficulties in the social domain and the impact of diabetes on their lives while
      staff saw diabetes primarily as a pathophysiological problem with impact on
      patients' physical bodies. This study's importance rests on its clear
      articulation of significant differences between patients' and staffs' models even
      when they are similar in demographic characteristics.

PMID- 8146717
TI  - The relevance of drug injectors' social and risk networks for understanding and
      preventing HIV infection.
AB  - Focusing on the social environment as well as the individual should both enhance
      our understanding of HIV transmission and assist in the development of more
      effective prevention programs. Networks are an important aspect of drug
      injectors' social environment. We distinguish between (1) risk networks (the
      people among whom HIV risk behaviors occur) as vectors of disease transmission,
      and (2) social networks (the people among whom there are social interactions with
      a mutual orientation to one another) as generators and disseminators of social
      influence. These concepts are applied to analyses of data from interviews with
      drug injectors in two studies. In the first study drug injectors' risk networks
      converge with their social networks: 70% inject or share syringes with a spouse
      or sex partner, a running partner, or with friends or others whom they know.
      Qualitative data from interviews with injectors in the second study also show
      that the social relationships between drug injectors and members of their risk
      network are often based on long-standing and multiplex relationships, such as
      those based on kinship, friendship, marital and sexual ties, and economic
      activity. In the first study the vast majority of injectors, over 90%, have
      social ties with non-injectors. Injectors with more frequent social contacts with
      non-injectors engage in lower levels of injecting risk behavior. Risk settings
      may function as risk networks: injectors in this study who inject at shooting
      galleries are more likely than those who do not to rent used syringes, borrow
      used syringes and inject with strangers. Since the adoption of a network approach
      is relatively new, a number of issues require further attention. These include:
      how to utilize social networks among drug injectors to reduce risk through peer
      pressure; how to promote risk reduction by encouraging ties between injectors and
      non-injectors; and how to integrate biographical and historical change into
      understanding network processes. Appropriate methodologies to study drug
      injectors' networks should be developed, including techniques to reach hidden
      populations, computer software for managing and analyzing network data bases, and
      statistical methods for drawing inferences from data gathered through dependent
      sampling designs.

PMID- 8146718
TI  - Social networks and infectious disease: the Colorado Springs Study.
AB  - The social network paradigm provides a set of concepts and methods useful for
      studying the structure of a population through which infectious agents
      transmitted during close personal contact spread, and an opportunity to develop
      improved disease control programs. The research discussed was a first attempt to
      use a social network approach to better understand factors affecting the
      transmission of a variety of pathogens, including hepatitis B virus (HBV) and
      human immunodeficiency viruses (HIV), in a population of prostitutes, injecting
      drug users (IDU) and their personal associates in a moderate-sized city (Colorado
      Springs, CO). Some of the challenges of studying large social networks in
      epidemiological research are described, some initial results reported and a new
      view of interconnections in an at risk population provided. Overall, for the
      first time in epidemiologic research a large number of individuals (over 600)
      were found connected to each other, directly or indirectly, using a network
      design. The average distance (along observed social relationships) between
      persons infected with HIV and susceptible persons was about three steps (3.1) in
      the core network region. All susceptibles in the core were within seven steps of
      HIV infection.

PMID- 8146719
TI  - Preterm birth, low birthweight and the stressfulness of the household role for
      pregnant women.
AB  - Whilst there is substantial, if inconclusive, literature on the association
      between psychosocial factors and birth outcomes, the relationship between
      persistent stressful aspects of daily life and birth outcomes has not been
      studied. This paper reports on the association of preterm birth and low
      birthweight with the psychosocial stresses of the household role. Three hundred
      and ninety three women who had completed one successful pregnancy (para 1) who
      booked for antenatal care in a single Glasgow hospital completed questionnaires
      at 20 and 30 weeks gestation and measures of perceived difficulties with the
      household role and of the frequency of negative feelings about participation in
      the role were obtained. Risks of preterm birth and low birthweight were
      associated with the measures of perceived difficulties at 20 and 30 weeks
      gestation. The association was strongest for the measure taken at 20 weeks where
      the odds ratio for those experiencing high levels of perceived difficulty were
      2.86 (95% CI = 1.05 - 7.76) for preterm birth and 4.70 (95% CI = 1.53 - 13.38)
      for low birthweight. Although the frequency of negative feelings about the
      household role were strongly associated with the level of perceived difficulties,
      it was not associated with either preterm birth or low birthweight. The gradients
      of risk associated with problems in the household role were maintained within
      categories of socio-economic indicators (social class, housing tenure and low
      income) and self-reported smoking, suggesting that the risks are independent of
      these other risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146720
TI  - Death for sale: a study of drug poisoning and deaths in Nigeria.
AB  - Drug availability, distribution and control are major concerns in health
      development. In contending that the concern in Nigeria now is as much with the
      availability of, as well as the dangers in drugs, this essay examines the 1990
      paracetamol poisoning which resulted in the death of 109 children. It is
      explained that this tragedy, and others before it, are more fully understood
      within the context of a seemingly free-for-all drug scene on the one hand, and a
      health care system which excludes the majority on the other. The implication of
      this "drug swindling", of which the paracetamol tragedy is a part, are discussed.
      We conclude that whereas more meticulous self regulation will most certainly
      provide a greater safeguard against recurrence, the war on counterfeit and
      poisonous drugs can hardly be won without consumer initiative and more effective
      regulatory system.

PMID- 8146721
TI  - [Bronchial hypersensitivity in Sjogren's syndrome].
AB  - It has been reported that Sjogren's syndrome has various pulmonary involvement
      including lymphoid interstitial pneumonia, lung fibrosis and various pulmonary
      manifestation. And some abnormalities in respiratory function have been pointed
      out. Bronchial hypersensitivity has been indicated in patients with bronchial
      asthma. It has been revealed that it plays an important role in pathogenesis of
      bronchial asthma. Recently, some authors reported bronchial hypersensitivity in
      patients with Sjogren's syndrome. We studied bronchial responsiveness to
      methacholine by using astograph in patients with Sjogren's syndrome. The patients
      are 25 subjects with Sjogren's syndrome. Bronchial hypersensitivity was seen in
      15 patients (60%). And it's pattern was more slight than it of bronchial asthma
      patients. Our results show bronchial hypersensitivity in Sjogren's syndrome which
      has been pointed out recently. It may be due to an alteration of bronchial
      epithelium secondary to lymphocytic inflammation and damage of bronchial glands.

PMID- 8146722
TI  - [Prognosis of interstitial pneumonitis (IP) in polymyositis (PM)/dermatomyositis
      (DM)].
AB  - IP, the major complication of PM/DM, is closely related to the life of these
      patients. In this study the course and prognosis of IP associated with PM/DM were
      investigated. Thirty IP patients with PM/DM were divided into 4 groups according
      to the course of IP. Clinical manifestations, laboratory data, chest radiographs
      and treatment were examined retrospectively. Eleven cases improved (Group I), 11
      cases were exacerbated (Group E), 3 cases were unchanged (Group U), 2 cases died
      due to rapid progression of IP (Group D) and 3 cases dropped out. Both Group D
      patients were middle aged female DM patients without CPK elevation. All cases
      were treated with corticosteroids. The clinical manifestations, laboratory data,
      chest radiographs and initial dose of corticosteroid were not markedly different
      between Group I and E. The total dose of corticosteroids during the first 3
      months tended to be higher in Group I than in Group E. Unlike idiopathic
      interstitial pneumonitis, the decrease in lung volume on chest radiographs
      improved after the treatment in 5 cases. We conclude that IP associated with
      PM/DM should be treated initially with high doses of corticosteroids.

PMID- 8146723
TI  - [Pulmonary functions in patients with progressive systemic sclerosis].
AB  - We studied the correlations of pulmonary function with clinical symptoms or
      autoantibody profiles in patients with progressive systemic sclerosis (PSS).
      Percent vital capacity (% VC) was low in 40% of PSS patients and percent
      diffusing capacity of carbon oxide (% DLCO) was decreased in 76% of the patients.
      Eighty-five percent of the patients had abnormal pulmonary functions. The % DLCO
      was significantly low in male patients compared with female patients. The
      arterial partial pressure of oxygen (PO2) in patients with esophageal
      hypomotility was significantly lower than those without esophageal hypomotility.
      PSS with Sjogren's syndrome (SS) showed a significant decrease of the % VC (p <
      0.05) and PO2 (p < 0.05), and of lung fibrosis was frequent in the patients
      compared with those without SS. Pulmonary fibrosis was recognized in 63% of PSS
      patients and was more frequent in the patients with anti-Scl-70 antibody than
      those without the antibody. The annual decrease of VC was 62 ml in PSS patients,
      and that of DLco was 0.12 ml/min/mmHg. The annual decrease of VC was more
      prominent in the PSS patients with severe pulmonary fibrosis or anti-Scl-70
      antibody. The decrease of VC, however, was mild in the patients with anti-RNP
      antibody compared with those without the antibody.

PMID- 8146724
TI  - [Association of antiphospholipid antibodies with valvular heart disease in
      patients with systemic lupus erythematosus].
AB  - The purpose of this study was to evaluate the association of antiphospholipid
      antibodies with the valvular lesions in patients with systemic lupus
      erythematosus (SLE). Two-dimensional and color Doppler echocardiographic studies
      were performed in 65 patients with SLE. Antiphospholipid antibodies were assayed
      in each patient using two methods: anticardiolipin antibody and lupus
      anticoagulant. Valvular lesions were observed in 43 patients (66.2%). Mitral or
      aortic regurgitation (MR or AR) were recognized in 37 patients (56.9%). Moderate
      or severe MR were significantly associated with antiphospholipid antibodies
      (20.0%, p < 0.01) compared with patients without antiphospholipid antibodies
      (2%). Four of nine patients with moderate to severe AR or MR developed cerebral
      infarctions or digital infarctions. It is suggested that there may be a causal
      link between antiphospholipid antibodies and moderate to severe valvular lesions
      in SLE.

PMID- 8146725
TI  - [Cortical atrophy and higher cortical dysfunction in systemic lupus
      erythematosus].
AB  - The relationships between cortical atrophy and higher cortical dysfunction in
      systemic lupus erythematosus (SLE) were investigated. The subjects were 27
      females, right-handed patients with SLE. None of them had a history of cerebro
      vascular disorders. The CT index of cortical atrophy included Huckman number,
      Evans' ratio, Ventricular index, and Cella-media index calculated from the brain
      CT. As controls, 27 age- and sex- matched, healthy subjects were studied and
      compared with the SLE group. All underwent the following neuropsychological
      examinations: intelligence and mental state, linguistic function, and recognition
      and praxis. As a result, Huckman number and Evans' ratio were significantly
      higher in the SLE group than in controls, clearly showing evidence of cortical
      atrophy. With regard to the relationships between cortical atrophy and
      neuropsychological tests, there were significant relationships between digit span
      and Huckman number and Evans' ratio, and between word fluency and Evans' ratio.
      These findings suggested that the atrophy of frontal lobe was characteristic in
      SLE, being associated with dysfunction of frontal lobe.

PMID- 8146726
TI  - [Behcet's disease in childhood--case reports and review of literature].
AB  - Two childhood with Behcet's disease were reported. To evaluate the clinical
      features of Behcet's disease in childhood, fifty eight case studies (domestic; 19
      cases, world-wide; 39 cases) were examined from the literature including two
      cases in our clinics. Oral ulcers (100%), genital ulcers (82.8%), skin
      manifestations (77.6%), and articular involvement (51.7%) were frequently found
      as seen in adult cases. Gastrointestinal manifestations were more common in
      childhood than in adults (50.0% vs. 29.3%). However, ocular inflammatory disease
      was less frequently seen in pediatric patients as opposed to adults. Three fourth
      of children with Behcet's disease was effectively treated with oral or
      intravenous prednisolone. These findings suggested that the criteria for
      childhood Behcet's disease will be necessary for early and proper diagnosis.

PMID- 8146727
TI  - [Three cases of Castleman's disease mimicking the features of collagen disease].
AB  - We report three cases of Castleman's disease mimicking the features of collagen
      disease. Case 1: A 39-year-old woman presented with intermittent arthralgia and
      fever. Laboratory findings were positive results for antinuclear antibody (80x
      speckled type), the LE test, anti-SSA antibody, anti-RNP antibody, and Coombs
      test. The patient was suspected to have systemic lupus erythematosus (SLE) or
      Sjogren syndrome, but a lymph node biopsy revealed the plasma cell type of
      Castleman's disease. Steroid treatment led to resolution of her symptoms. Case 2:
      A 60-year-old man with mixed type Castleman's disease had proteinuria with renal
      dysfunction, autoimmune thrombocytopenia, antinuclear antibody, anti-RNP
      antibody, anti-DNA antibody and anti-cardiolipin antibody. The patient was
      suspected to have SLE but cervical lymph node biopsy revealed the mixed type of
      Castleman's disease. Symptoms were not controlled with steroid therapy. He
      developed renal failure that required for hemodialysis and died of
      gastrointestinal bleeding due to severe thrombocytopenia. Case 3: A 46-year-old
      woman had Raynaud's phenomenon, sclerodactylia, and nail fold bleeding.
      Laboratory tests were revealed positive for antinuclear antibody, anti-ENA
      antibody, and LE cell preparation. Radiographic study showed multiple masses in
      the retroperitoneal spaces, which necessitated laparotomy. Firstly, the patient
      was suspected to have systemic sclerosis or mixed connective tissue disease
      (MCTD). A biopsy revealed the hyaline-vascular type of Castleman's disease. The
      serum level of IL-6 by ELISA was high in all of three cases. In case 1, symptoms
      improved and the IL-6 level normalized after steroid treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8146728
TI  - [Collagen diseases complicated with myelodysplastic syndrome (MDS)--report of
      three cases].
AB  - We presented three cases of collagen diseases complicated with myelodysplastic
      syndrome (MDS). To our knowledge, MDS following collagen disease is very rare,
      and only seven cases have been reported previously. First case (a 40-years old
      woman) had suffered from rheumatoid arthritis, systemic lupus erythematosus and
      Sjogren's syndrome for 16 years. Second case (a 65-years old woman) had suffered
      from rheumatoid arthritis for 15-years. Third case (a 63-years old woman) had
      suffered from progressive systemic sclerosis for 16 years. These patients
      developed MDS. After onset of MDS, cytopenia progressed rapidly within half a
      year. In the types of MDS, case 1 and case 2 had refractory anemia and case 3 had
      refractory anemia with excess of blasts and a preleukemic state. Case 2 had a
      clonal abnormality of haemopoietic stem cells. It is unlikely that MDS in our
      cases are caused by mutant agents or irradiation. These results suggest MDS may
      be contributed to long-term immunodysfunction found in these collagen diseases.

PMID- 8146729
TI  - [Hypopituitarism associated with empty sella after steroid pulse therapy in a
      patient with SLE].
AB  - A case of systemic lupus erythematosus (SLE) complicated with hypopituitarism
      after steroid pulse therapy is reported. A 46-years-old-female with a history of
      SLE starting in 1975 was admitted to our hospital in February 1991 for lupus
      nephritis. Steroid pulse therapy, 1000 mg methyl-prednisolone for 3 successive
      days as one therapy unit, was administered. Proteinuria improved remarkably,
      however, general fatigue and headache appeared 2 weeks after initiation of
      therapy. Endocrinological examination revealed hypopituitarism including the
      levels of TSH, FSH, GH and ACTH. The secretion of FSH and LH gradually improved
      after replacement therapy of dried thyroid. MRI examination of the brain revealed
      an empty sella. It is known that pituitary tumor, cerebrovascular accident and
      autoimmune lymphocytic hypophysitis cause hypopituitarism. In this case, it is
      unlikely that the pulse therapy may be responsible for the infarction of the
      anterior pituitary artery furthermore, there has been no articles describing such
      incidence after steroid pulse therapy. This case may be indicative of a very rare
      case in which the empty sella might have been exacerbated by the pulse therapy in
      the causation of hypopituitarism.

PMID- 8146730
TI  - [Protein-losing enteropathy and cerebral infarction associated with systemic
      lupus erythematosus].
AB  - A 26-year old woman, who was diagnosed as having systemic lupus erythematosus at
      the age of 23 year old, presented diarrhea and headache. She showed severe
      hypoproteinemia (serum total protein 3.7 g/dl, serum albumin 1.4 g/dl) and
      hyperlipidemia. She revealed to have protein-losing enteropathy with the result
      of alpha-1-antitrypsin clearance test using stool. Increase of prednisolone
      improved the loss of albumin into the bowel and abnormal laboratory findings. She
      also showed watershed infarction in the area of middle cerebral artery and
      posterior cerebral artery. Protein-losing enteropathy is a rare complication of
      SLE, only 18 cases are available on literature. No case is found to have cerebral
      infarction in patients with protein-losing enteropathy associated with SLE. It is
      known that blood levels of anticoagulation factors decrease in protein-losing
      enteropathy due to the leakage of plasma protein into intestinal lumen. Serum
      antithrombin III was decreased in this case. Hyperlipidemia found in this case
      seems to be caused by same mechanism in nephrotic syndrome. Lupus anticoagulant
      was also positive in this patient. These factors seems to be related to the
      occurrence of cerebral infarction. This case suggests the possibility of cerebral
      infarction in patients with protein-losing enteropathy in SLE.

PMID- 8146731
TI  - [Effects of combined administration of prednisolone and mizoribine in the course
      of remission for SLE children with nephritis].
AB  - Since oral steroid therapy was introduced for SLE, the long-term prognosis of the
      patients has been significantly improved. Adverse effects of the drug, however,
      are inevitable for these patients. The characteristic of the adverse effects
      especially for the child case is the suppression of linear growth. In order to
      prevent these undesirable effects and to improve their quality of life (QOL), we
      had introduced the methylprednisolone pulse therapy for SLE in children as both
      an initial and a relapse therapy. Although this therapy improved QOL of the
      patients significantly, there was little benefit for the growth disturbance.
      Then, we have introduced Mizoribine in addition to prednisolone (PSL) therapy for
      more than 18 months in three SLE children with lupus nephritis. In this trial,
      the combination therapy was effective for the decrease of urinary protein in one
      case, and for the reduction of a dosage of oral PSL in one case. In other case,
      MZR showed only partial immunosuppression. Thus, we concluded that there was a
      limitation with this combination therapy, however, it is one of the worthy
      therapy to be tried in SLE children with nephritis.

PMID- 8146732
TI  - [Analysis of outcome measurement in the surgical treatment of rheumatoid
      patients].

PMID- 8146733
TI  - [Epidemiological methods in chronic diseases: especially in collagen diseases].

PMID- 8146734
TI  - [Combination therapy of slow-acting antirheumatic drugs].

PMID- 8146735
TI  - Lateral approaches to the petroclival region.
AB  - The microsurgical anatomy that provides the basis for dealing with lesions
      arising in the petroclival region was reviewed in 15 adult cadaver heads and 25
      dry skulls. The eight surgical approaches studied were the retrosigmoid, extreme
      lateral transcondylar, translabyrinthine, transcochlear, combined supra and
      infratentorial presigmoid, subtemporal anterior transpetrosal, subtemporal
      preauricular infratemporal, and the postauricular transtemporal approach.
      Considerations important in the selection of these approaches are discussed.
      Special attention was directed to the course of the facial nerve and internal
      carotid artery in the temporal bone and the major venous pathways draining the
      region.

PMID- 8146736
TI  - The transsylvian approach to middle cerebral artery bifurcation/trifurcation
      aneurysms.
AB  - A transsylvian approach to treat aneurysms located at the
      bifurcation/trifurcation of the middle cerebral artery (MCA) is described. This
      surgical route traces a distal MCA branch retrogradely into the Sylvian fissure
      whereupon a secondary MCA branch and the main stem of the MCA (M1) are identified
      before aneurysm clipping. The advantages, and disadvantages of this approach are
      discussed. The transsylvian route should be considered as an alternative to the
      traditional pterional approach, which utilizes proximal to distal dissection of
      the MCA, in situations when the M1 is long or when the pterional approach is
      inadvisable.

PMID- 8146737
TI  - Management of a giant middle cerebral artery fusiform serpentine aneurysm with
      distal clip application and retrograde thrombosis: case report and review of the
      literature.
AB  - Giant fusiform aneurysms are rare vascular anomalies that due to their size are
      often difficult to manage. We describe one such aneurysm that was managed with a
      superficial temporal to middle cerebral artery bypass followed by the application
      of a single clip just distal to the vascular dilation. Follow-up angiography has
      shown aneurysm obliteration by the process of retrograde thrombosis.

PMID- 8146738
TI  - Subarachnoid hemorrhage from cavernous angioma of the cauda equina: case report.
AB  - A case of spinal subarachnoid hemorrhage from a cavernous angioma of the cauda
      equina is reported. The patient was a 28-year-old man who complained of a sudden
      low-back pain and neck stiffness. Laminectomy at L1-L2 was performed with total
      removal of the tumor.

PMID- 8146739
TI  - Intracranial extradural hydatid cysts: report of three cases.
AB  - Intracranial extradural hydatid cysts are a rare occurrence with unclear
      pathogenesis. Three different cases are reported and the postoperative courses
      are discussed. Of the 11 cases found in the literature, all eight cases whose sex
      and age were reported are men, and seven of the eight are clustered in between
      the second and fourth decades.

PMID- 8146740
TI  - Extramedullary glioma of the cervicodorsal spinal cord--a case report.
AB  - Extramedullary gliomas are rare and usually have an intramedullary component. A
      case of extramedullary astrocytoma without intramedullary mass in an adolescent
      girl has been reported.

PMID- 8146741
TI  - Spinal canal stenosis at the level of the atlas: case report.
AB  - We describe a rare case of cervical canal stenosis at the level of the atlas,
      presenting with cervical myelopathy as an initial symptom. A 55-year-old man was
      admitted to our hospital with a 4-month history of gait disturbance and
      clumsiness in both hands. He had no history of trauma, and showed left-sided
      hemihyperesthesia and mild quadriplegia with exaggerated deep tendon reflexes.
      Plain cervical tomography revealed marked spinal canal stenosis, with the
      diameter of 8.0 mm at the level of the atlas. Magnetic resonance imaging
      demonstrated severe compression of the spinal cord at the atlas, with an
      extensive high intensity area indicating edema on T2-weighted images. The patient
      showed an excellent recovery after laminectomy of the atlas combined with
      decompression of the lower posterior fossa of the foramen magnum and dural
      plasty.

PMID- 8146742
TI  - Development of post-traumatic cysts in the spinal cord of rats-subjected to
      severe spinal cord contusion.
AB  - To study the development of post-traumatic spinal cord (SC) cysts, and their fine
      anatomic characteristics, rats were subjected to severe SC contusion. Specimens
      were analyzed from day 1 to 1 year post-injury. Using conventional light, and
      transmission and scanning electron microscopy, three stages were typified,
      namely: necrosis, repair, and stability. The final cell composition and thickness
      of the cyst walls were not uniform. Astrocytes, fibroblasts, ependymal cells, and
      collagen fibers were the main constituents. Chronic inflammatory cells were also
      observed. The neuropathologic characterization of posttraumatic SC cysts could be
      useful in planning strategies for SC reconstruction at different times post
      injury.

PMID- 8146743
TI  - Transient peduncular hallucinations secondary to brain stem compression by a
      medulloblastoma.
AB  - Almost all peduncular hallucinations have been described in patients with
      intrinsic lesions of the midbrain. An as yet unreported case of peduncular
      hallucinosis caused by posterior compression of the midbrain by a medulloblastoma
      in a 16-year-old boy is provided. The hallucinations and associated symptoms only
      ceased after removal of the tumor.

PMID- 8146744
TI  - Does the patient come first?

PMID- 8146746
TI  - The growth of neurosurgery.

PMID- 8146745
TI  - Department or section of a department for neurosurgery.

PMID- 8146747
TI  - Swelling in the left fronto-temporal region.

PMID- 8146748
TI  - International comparisons of mortality rates.

PMID- 8146749
TI  - 1992 hospital charges for two major surgical procedures for cardiovascular
      diseases. Part I: Coronary artery bypass grafts.
AB  - During 1992, charges for coronary artery bypass graft (CABG) surgeries among
      MetLife group health insureds and dependents averaged $44,200. Among the 21
      states with 20 or more CABGs, the average charges ranged from a high of $61,990
      in California to a low of $34,290 in Ohio. Three-fourths of the total charges
      billed to MetLife were due to the hospital bill, with fairly wide variation
      between states. Hospital charges in New York accounted for 62 percent of the
      total bill whereas those in neighboring Pennsylvania averaged 80 percent of the
      bill for a CABG. Physician charges averaged $11,260 across the country and ranged
      from a high of $16,620 in Connecticut to a low of $8,850 in Oregon. Hospital stay
      averaged nine days, with confinement ranging from seven to 12 days. Room and
      board charges accounted for 31 percent of the hospital bill and averaged $10,170
      across the country.

PMID- 8146751
TI  - 1992 hospital charges for two major surgical procedures for cardiovascular
      diseases. Part II: Cardiac catheterization.
AB  - In-hospital cardiac catheterization (CC) charges among MetLife group health
      insureds and their dependents averaged $10,880 during 1992. Among the 24 states
      in which 50 or more CCs were performed, the average total charges ranged from a
      low of $6,400 in Maryland to a high of $17,600 in California. Not only were these
      California charges 2.75 times higher than the lowest ones, they were also 62
      percent higher than the U.S. average. Illinois registered the second highest
      average total charges ($14,340) and Wisconsin reported the second lowest
      ($7,320). On average, the hospital portion of the CC charges accounted for 82
      percent of the total, ranging from 86 percent of the total charges in California,
      Colorado and Alabama to 70 percent in New York and 71 percent in New Jersey.
      Ancillary fees accounted for 62 percent of the total hospital charges and
      averaged $5,530 across the country. Physician fees averaged $2,000 for a CC in
      1992, with these charges being the highest in California ($2,550--28 percent
      above the U.S. average) and the lowest in South Carolina ($1,300--32 percent
      below the norm for the country). Length of stay averaged four days with very
      little variation evident between regions or states.

PMID- 8146750
TI  - International cancer mortality comparisons.
AB  - Decreases, if any, in mortality from all forms of cancer combined have been
      relatively small in the past few decades. In fact, until recently, the U.S. age
      adjusted cancer mortality rates have trended slowly upward, while other countries
      showed mixed results. Roughly half of the 15 countries studied experienced higher
      cancer death rates. Analysis of U.S. mortality by age group revealed a dramatic
      split in the pattern of death rate changes. Both men and women aged 55 and over
      generally recorded increases in mortality between 1970 and 1980, as well as
      between 1980 and 1990, while rates among younger persons declined. During this
      period mortality from respiratory cancer increased rapidly, especially among
      women.

PMID- 8146752
TI  - Developments in health care costs--an update.
AB  - During 1993, an estimated $910 billion was spent on health care in the United
      States. Health care expenditures, as a whole, continued to show a slower rate of
      growth in 1993 than in 1992. The medical care Consumer Price Index rose 6.0
      percent in 1993 and is projected to increase only about 5.7 percent in 1994. HMO
      enrollment increased 7.3 percent between 1991 and 1992, with an estimated 41.4
      million participants. In terms of per capita spending, health care expenditures
      in the United States are more than twice the average for the 24 industrial
      nations that make up the Organization for Economic Cooperation and Development
      (OECD). As the health care reform debates continue, evidence indicates that
      market forces are beginning to exert an influence on the health care sector of
      the economy. Further, regardless of what final form health care reform will take,
      the role of managed care will probably continue to increase.

PMID- 8146753
TI  - [Shoes in sports].

PMID- 8146754
TI  - [Cushioning versus stability].
AB  - Cushioning and stability are still key words for functionally constructed sport
      shoes. The goal of this investigation is to present and discuss the possibilities
      and limits of these shoe properties. Here, stability is not regarded as rigidity
      (like in a ski boot), but as a "dynamic stability" in the sense of functionality
      which supports the foot under load in such a manner that no unphysiological
      movements are provoked. Cushioning (in physics terminology: "damping") is defined
      to reduce and eliminate (kinetic) energy. When considering the impact peak in
      running, this peak can be reduced by using hard shoe soles with large heel
      flares. However, by doing that, large levers are introduced which produce an
      increased distance to decelerate the touchdown. This is basically the opposite of
      dynamic stability. Current shoe sole materials (homogeneous/isotropic) improve
      the "cushioning" but enhance the instability. New ways of shoe construction using
      more sophisticated anisotropic materials may lead out of this dichotomy.

PMID- 8146755
TI  - Friction--slipping--traction.
AB  - The minimum translational traction requirements of outsoles for shoes used for
      walking, running, and activities involving lateral movements are presented. Since
      it will be shown that the classical friction relationships described by Coulomb
      do not always apply to the elastomeric materials used in modern day athletic
      footwear, empirical measures of the traction characteristics of candidate
      materials and designs must be made. A physical traction testing device has been
      developed to make measurements of the traction characteristics of shoe outsoles
      will be described. This device quantifies both translational and rotational
      traction characteristics. Examples of factors affecting both of these variables
      are presented. Combining a knowledge of the traction characteristics of materials
      and designs and the factors influencing traction with knowledge of the traction
      requirements of different activities permits the matching of appropriate outsoles
      to shoes used for specific activities.

PMID- 8146756
TI  - [Biomechanical considerations of impact forces and foot stability in running].
AB  - The interaction between "man-shoe and surface" is presented as a model to discuss
      the complexity of human locomotion. Only if the physiological system "man"
      interacts positively with the physical requirements of shoe and surface quality
      running will become effective and economical. Especially during the early ground
      contact phase the hardness of the shoe construction determines the height of the
      vertical impact load. These adaptations have consequences in the emg amplitudes
      during the stretch activation phase of the contact. Comparing various jogging
      shoes with altered construction properties it can be shown that the "hardness" of
      the shoe material is well adapted by the variation in the emg amplitude. The
      influence of the amount of pronation on the impact forces has been confirmed in a
      separate study. Increased pronation resulted in an increased emg amplitude in the
      extensor muscles whereas activation in the flexor muscles was decreased. By means
      of different shoe and insole constructions it is possible to adjust the "man-shoe
      surface" interaction to an optimum to carry loads by muscles, joints and
      ligaments and to avoid overuse and injuries.

PMID- 8146757
TI  - [Children's shoe: a miniature version of the adult shoe?].
AB  - The question arising from this subject, could be answered with "Yes" and "No",
      since this issue is interpreted differently by footwear manufacturers. During the
      last 10 years the scientists have achieved essential knowledge concerning the
      requested standards of children's footwear. These results verify that children's
      footwear needs to have other characteristical features than adult's footwear. The
      requested standards on a healthy children's shoe result from the exceptional
      function (intensity and many-sided motor activity) and the anatomy (elasticity,
      shape and state) of a child's foot, which is, in contrast to an adult's foot,
      still developing. Due to these facts there are special requirements and features
      regarding the fitting, the flexibility and the information. This is explained on
      some examples.

PMID- 8146758
TI  - [Criteria for biomechanical tests for athletic shoes].
AB  - In recent years, comparative sport shoe tests have resulted in an improvement of
      athletic footwear quality. Examples demonstrate the value and the limits of
      material tests, biomechanical investigations and subjective wear test
      evaluations. Biomechanical experiments have the primary goal to analyse sports
      shoe function with regard to shoe properties to prevent injuries. Rear foot
      pronation and supination measurements, in-shoe pressure distribution analyses,
      and the registration of ground reaction forces as well as tibial accelerations
      are valuable in the process of biomechanical evaluation. Material tests can be
      used to determine production quality between shoes and midsole material
      deterioration in used shoes. Wear tests with subjective evaluation are necessary
      for the judgement of shoe properties (e.g., shoe fit) which cannot be measured by
      biomechanical or material test methods.

PMID- 8146759
TI  - [Criteria for running (jogging) shoe tests].
AB  - Shoes for jogging are presently being tested by a great many institutes using
      widely divergent criteria and according to a plethora of different interests, and
      hence the assessments and test results may be poles apart and even contradictory.
      Most of the tests are based on much too short stress periods and either disregard
      biomechanical properties entirely or determine them via methods that must be
      classified as questionable. Today no manufacturer offers models one could
      definitely classify as excellent or deficient. A shoe for jogging may be optimal
      for one jogger and fatal for another. The following article sets criteria
      yielding two important kinds of information: on the one hand, an analysis of weak
      points that will help the manufacturer by telling him where he must improve his
      product, and on the other hand target-group oriented usage recommendations for
      the benefit of the consumer (jogger) that help him to find the shoe that suits
      him best among a never-ending conglomerate of sports shoes.

PMID- 8146760
TI  - [External stabilizers for the foot].
AB  - The stability in the lateral direction is particularly important in indoor sports
      as well as tennis, where the frequency of injury at the lateral aspect of the
      ankle is considerably high (according to various sources between 20-30%). The
      goal of the present work was to discuss the reasons of instability at the ankle
      and the effect of external stabilizers. In a number of investigations the
      stability was measured via film analysis during sports activities in barefoot and
      shoe conditions. It was concluded that stability and blocking of a movement
      cannot be regarded as equal. The latter restricts necessary movements of the foot
      at the ankle and may also provoke large internal forces elsewhere. Negative in
      respect to stability are stiff and thick shoe soles, positive are: the torsional
      ability of the sole, softness of the shoe sole edge, the link between the shaft
      and the sole, shaft height, taping and bracing.

PMID- 8146761
TI  - [The athletic shoes as a therapeutic aid].
AB  - Sports shoe research discovered several possibilities of influencing the heel-to
      toe walking behaviour of the foot which can be made use in the construction of
      therapeutic shoes. Early functional therapy aims at imparting moderate load
      stimuli to the injured and/or surgically reconstructed tissue to ensure quicker
      orientation of the collagen fibres of the cicatricial structures and an improved
      blood supply to the tissue. Modified sports shoes with variable mobility
      restriction and functional heel-to-toe walking support of the foot have become a
      meaningful therapeutic aid in the treatment of fibular ligament lesions and
      injuries to the Achilles tendon, both in orthopaedic and neurological problems
      requiring support of the sequential movements of the foot (arthrodeses,
      arthroses, peroneal paralyses [dangle foot], etc.) Early functional after
      treatment ensures that moderate load stimuli are exercised on the tissue while
      avoiding peak tensions, thus shortening the rehabilitation period with minimal
      inactivity atrophies and hence enabling quicker return to normal daily
      activities.

PMID- 8146762
TI  - [Arterial pressure, physical activity and physical work capacity].
AB  - A representative population sample was studied to elucidate relationships of
      arterial pressure (AR) with muscular performance (MP) and arterial hypertension
      risk factors. Power working capacity (PWCx) was measured by means of exercise
      tolerance test at rest, under physical loading and after the exercise. The
      findings were processed using a multivariate step-by-step regression analysis
      which established independent relations between exercise and postexercise MP and
      arterial hypertension. In normal and hypertensive males a rise in systolic
      pressure (SP) after the initial exercise (load 1) was dependent on PWC1 after
      more intensive exercise (load 2) on relations of MP with heart rate, SP and
      diastolic pressure (DP). In hypertensive males the SP elevation depended also on
      the age, B. W. index and heart rate. In normal AP males a DP rise depended on
      PWC2 and MP, the increment being limited by relationships between MP, DP, heart
      rate and SP. In hypertensive males the influence of PWC1 is defined through a SP
      rise after load 1. In normal AP and hypertensive females PWC1 is decisive for a
      SP rise. In normal AP females growth of DP after load 2 was dependent on PWC2 in
      relation to heart rate growth after load 2, while in hypertensive females PWC1
      resulted in DP elevation after load 1. On comparison of the groups with normal
      and high AP the degree of AP increment under exercise depended on the relations
      of MP with heart rate, SP and DP.

PMID- 8146763
TI  - [Familial and nonfamilial forms of arterial hypertension].
AB  - Family and nonfamily hypertension (FH, NFH) forms were studied among patients
      with essential hypertension and symptomatic hypertension. Na-Li countertransport
      in FH patients against NFH ones proved significantly increased. However, CA2+
      velocity mediated by Ca ATPase in them was less than in NFH subjects. Plasma
      filtration and hemosorption reduced arterial pressure more effectively in NFH
      patients. Surgical treatment in patients with symptomatic arterial hypertension
      is more successful in reducing arterial pressure in NFH subjects.

PMID- 8146764
TI  - [A method for determining individual nifedipine sensitivity in treating
      hypertension patients].
AB  - Nifedipine antihypertensive effect was evaluated in 20 patients with essential
      hypertension. It was found to depend on pretreatment values of ADP-induced
      platelet aggregation response. The latter was studied with a new method of laser
      measurements of the aggregate radius sizes.

PMID- 8146765
TI  - [New approaches to the polyclinic assessment of physical work capacity in
      hypertension patients].
AB  - By using up-to-date mathematical methods, the authors studied exercise tolerance
      in 324 hypertensive patients. New approaches are validated to estimation of motor
      activity and its intensity in hypertensive subjects. The mathematical model
      provides reliable orientation in physical performance in the above patients as
      well as in their reference to the functional classes. The model is thought
      appropriate for wide introduction into outpatient clinical practice.

PMID- 8146766
TI  - [The differential diagnosis of the ECG changes in ischemic heart disease combined
      with arterial hypertension (the data from precordial mapping)].
AB  - The authors have developed the algorithm for differential diagnosis of coronary
      heart disease associated with arterial hypertension. The algorithm was devised
      using the comparative data of precordial mapping made for 29 and 60 coronary
      disease patients with arterial hypertension and coronary stenosis without left
      ventricular myocardial cicatrices, hypertrophy and dilatation, respectively, as
      well as for 30 hypertensive subjects without coronary angiography signs of
      coronary stenosis, but with left ventricular hypertrophy established at
      echocardiography. Sixty normal subjects served as control. The algorithm
      sensitivity reached 70%, specificity 73%.

PMID- 8146767
TI  - [Left ventricular function in patients with ischemic heart disease at the moment
      of acute myocardial ischemia induced by transesophageal cardiac
      electrostimulation].
AB  - Repeat transvenous multiphase left ventriculography was performed in 14 patients
      with coronary stenosis diagnosed by clinical and angiographic findings. The
      procedure was conducted before and in the course of transesophageal pacing. The
      latter provoked acute myocardial ischemia responsible for a wide range of left
      ventricular dysfunctions which are analyzed in the paper in terms of
      cardiomanometry parameters, cardiocycle energetic balance, diastolic function and
      local motions of the camera walls.

PMID- 8146768
TI  - [Genealogy and the clinical manifestations of familial hyperlipidemias types IIa
      and IIb].
AB  - To analyze genealogical and clinical characteristics of family hyperlipidemia
      type IIa and IIb, the author examined 40 probands and 179 close relatives. Blood
      lipid composition was investigated in 85 of them. Hyperlipidemia was found in 42
      examinees which is in accordance with previous findings on this trait
      inheritance. Sons inherit hyperlipidemia from their fathers more frequently than
      daughters (60.0% against 40.0%, respectively). Coronary heart disease and other
      related clinical conditions arose more frequently in probands than in their
      relatives with hyperlipidemia though 10-year mortality in them was actually the
      same: 20.0 and 18.6%, respectively.

PMID- 8146769
TI  - [The etiological aspects of the sick sinus syndrome].
AB  - A clinico-genetic study of sick sinus syndrome in Krasnoyarsk population
      established its prevalence as 0.296%. The disease affected females more
      frequently than males. The highest morbidity was registered at the age 60-69.
      Genetic evaluation demonstrated high hereditary predisposition to the syndrome as
      it developed in 60 out of 309 (19.4%) relatives of the patients, the inheritance
      being autosomal dominant and in part sex-limited. Females predominated among the
      disease-affected relatives and among those whose relatives had the syndrome. The
      syndrome is also age-related. The authors discuss the role of ischemic heart
      disease in the origin of sick sinus syndrome.

PMID- 8146770
TI  - [An outpatient study by stress echocardiography with dobutamine of myocardial
      function in patients with congestive heart failure (the first trial in Russia of
      the use of the dobutamine-echocardiography test)].
AB  - Dobutamin stress-echocardiography has been tried outpatiently in the diagnostic
      center for feasible use in functional assessment of the myocardium in patients
      with congestive heart failure class 3-4 by classification of New York Heart
      Association. Eleven outpatients (a mean age 56 +/- 8 years) with left ventricular
      dilatation and a reduction in the ejection fraction received an increasing dose
      of dobutamin (5-40 micrograms) min/kg in intravenous infusion in the course of
      which central hemodynamics and left ventricular segmental contractility were
      measured with two-dimensional and Doppler echocardiography. By the hemodynamic
      response to dobutamin infusion reflecting difference in the myocardial reserve,
      two groups of patients were identified. The authors suggest dobutamin Doppler
      echocardiography for use in outpatient setting as a safe and effective procedure
      for assessing contractile myocardial reserve and prognosis of congestive heart
      failure.

PMID- 8146771
TI  - [An evaluation of the effect of the sauna on the clinical, laboratory and
      psychological indices in rheumatoid arthritis].
AB  - The direct effect of sauna procedures was assessed in 196 patients with
      rheumatoid arthritis (RA) in minimal or moderate activity stage. Three
      temperature and humidity regimens were tested. The optimal conditions occurred at
      80 +/- 5 degrees C and relative air humidity 10-20%. Sauna produced a positive
      effect on locomotor system, psychoemotional status, alleviated pain. Clinico
      biochemical and immunological indices of the peripheral blood underwent
      insignificant transient shifts.

PMID- 8146772
TI  - [The content of interleukin-1 beta in the blood serum of patients with systemic
      lupus erythematosus and rheumatoid arthritis].
AB  - The enzyme immunoassay determined serum levels of interleukin-1 beta (IL-1 beta)
      in 35 patients with systemic lupus erythematosus (SLE) and 18 rheumatoid
      arthritis (RA) patients. In high activity of both SLE and RA as well as in the
      presence of fever, anemia, marked skin vasculitis IL-1 beta rose high, still
      higher levels being reported in patients with erosive joints compared to those in
      RA patients with initial stage of RA. Lower IL-1 beta content often marked
      nephropathy in both the diseases. Corticosteroids and cytostatics resulted in IL
      1 beta fall which was also established in 9 SLE and 3 RA patients in parallel
      with inhibition of the process activity.

PMID- 8146773
TI  - [The methodological aspects of identifying the etiological significance of
      anthropogenic pollution in the genesis of chronic bronchitis].
AB  - The paper is concerned with multifactorial assessment of the air anthropogenic
      contamination effect on development of chronic nonspecific pulmonary diseases,
      chronic bronchitis (CB) in particular. Methodological approaches to identify
      etiological significance of anthropogenic effects in CB genesis include
      measurements of the air contaminants, calculation of the total contamination
      index, selection of the study and control territories, analysis of medical
      documents, conduction of wide-scale medical examinations. CB developing in the
      conditions of the above contamination is characterized by obstructions,
      bronchospastic components, other separate or systemic disorders.

PMID- 8146775
TI  - [The nature and causes of the development of hypertension and the importance of
      the diagnosis of this nosological form for the prophylaxis and differentiated
      treatment of patients].

PMID- 8146774
TI  - [Atherogenesis in bronchial asthma patients: its relationship to the pathogenetic
      characteristics of the disease and to liver function (the clinico-biochemical
      aspects)].
AB  - Ten asthmatics in remission and aggravation of the disease were examined for:
      lipoprotein pre-beta, beta and alpha fractions, total cholesterol and its
      fractions in atherogenic and antiatherogenic lipoproteins with estimation of the
      atherogenicity coefficient, activity of 5-nucleotide hydrolase, acid phosphatase,
      gamma-glutamyl transpeptidase and alcohol dehydrogenase. The results were
      indicative of more active atherosclerotic process in the presence of blockade
      which changed the activity of hepatocyte membrane lipoprotein receptors, of
      simultaneous operation in bronchial asthma patients of infiltrative and cellular
      mechanisms of atherosclerosis.

PMID- 8146776
TI  - [A trial of the clinical use of intestinal dialysis in chronic kidney failure].
AB  - The authors analyze pilot experience with clinical introduction of intestinal
      dialysis in 7 uremic patients. Repeated sessions of the dialysis relieved some
      symptoms of uremic intoxication. The method may be of value in contraindications
      to chronic hemodialysis for chronic renal failure. The technique is easily
      performed and well tolerated by the patients. The investigations should be
      continued.

PMID- 8146777
TI  - [A case of the long-term observation of Burger-Grutz disease].
AB  - The authors observed Burger-Grutz disease (primary hyperchylomicronemia, painful
      recurrent xanthomatosis, hepatosplenomegaly, hyperglycemia) for 20 years in a 54
      year-old female patient. The disease ran a benign course. No marked vascular
      lesions, progressive atherosclerosis, diabetes mellitus arose. This is an
      original report of Burger-Grutz disease long-term course and life-long heparin
      treatment in this country.

PMID- 8146778
TI  - [The comparative characteristics of disease prevalence and the structure of
      mortality in women of reproductive age].
AB  - Incidence rate of some diseases and mortality have been analyzed basing on the
      examination of 714 females aged 18-50 and 176 fatal outcomes in 23-82-year-old
      females. The disease prevalence and death rate showed the trend to an increase
      with growing number of deliveries. Multiparas die more frequently of
      cardiovascular diseases the risk of which proved the highest in the group of
      multiparas over 45 years of age.

PMID- 8146779
TI  - [The use of the preparation bonefos in the combined therapy of multiple myeloma
      patients].
AB  - A clinical trial of a new drug bonefos (Leiras, Finland) in 13 patients with
      multiple myeloma confirmed its potent analgetic effect. Alleviation of ostealgia
      was seen as early as the treatment day 5-7. The drug inhibits the progression of
      skeletal tumor growth, reduces the frequency of bone fractures, normalizes
      calcium concentrations in the blood and urine. Side effects such as nausea and
      short-term epigastric pains occurred in 23% and 15.38% of the patients,
      respectively.

PMID- 8146780
TI  - [The results of using arteparon after orthopedic operations].
AB  - Arteparon was locally used in 87 patients after reconstructive surgery on the
      joints. Arteparon administration was conducted 2 weeks following corrective
      operations: arthrotomy, allo- and autoplasty, replantation of the limb segments,
      arthroplasty, one-pole endoprosthesis. The drug was introduced into the hip,
      knee, ankle, wrist joints. Follow-up 6-24-month results demonstrated due to the
      drug improvement of the surgical outcomes because of normalization of the
      internal joint medium and providing the conditions for the cartilage
      regeneration. Two courses of arteparon must be the minimum during one year.

PMID- 8146781
TI  - [Methods of active problem instruction in teaching polyclinic therapy at a
      medical institute].

PMID- 8146782
TI  - [The characteristics of using diuretics in elderly patients].

PMID- 8146783
TI  - [Lyme arthritis].

PMID- 8146784
TI  - [The epidemiology of spondylarthropathies among the native inhabitants of
      Chukotka (Eskimos and Chukchi). 1. The prevalence of spondylarthropathies among
      the Eskimos and the coast Chukchi].
AB  - To establish the prevalence of spondyloarthropathies among the indigenous
      population of Chukot Peninsula, a one-stage cross-sectional study was made with a
      direct medical examination of the natives of the two settlements of Eastern
      Chukot Peninsula: Sireniki and Novo-Chaplino where the main part of Eskimos live.
      During expedition, 640 natives aged over 6 years lived in both settlements (382
      and 258 respectively). 464 persons (72.5%) were examined. Of these, 7 persons
      (1.5%) were diagnosed to suffer from diseases belonging to the group of
      spondyloarthropathies: 2 persons (0.4%) had ankylosing spondyloarthritis, 2
      (0.4%) Reiter's syndrome, 2 undifferentiated spondyloarthropathies, and 1
      juvenile chronic arthritis. Of the 7 patients, 4 were Eskimos, 2 half-breeds and
      1 was a Chukchi man. The incidence of ankylosing spondyloarthritis among Eskimos
      amounted to 0.9%, Reiter's syndrome to 0.5%, and undifferentiated
      spondyloarthropathies to 0.5%. Thus the one-stage expedition examination of the
      indigenous population of Chukotka Peninsula (Eskimos and Chukchi) has shown that
      diseases belonging to the group of spondyloarthropathies are widely prevalent
      among Eskimos.

PMID- 8146785
TI  - [The cerebral blood circulation in patients with systemic lupus erythematosus and
      the antiphospholipid syndrome].
AB  - Ultrasonic duplex scanning was employed to examine cerebral circulation in 50
      patients suffering from significant lupus erythematosus (SLE). Of these, 25
      patients were with antiphospholipid syndrome (APS) and 25 were without APS. The
      patients with APS showed a decrease in the total cerebral circulation and a
      higher percentage of arterial blood flow asymmetry as compared to the patients
      without APS. The method expands potentialities of the diagnosis of central
      nervous system damage associated with SLE.

PMID- 8146786
TI  - [Diprophos--a new preparation for local antirheumatic therapy].

PMID- 8146787
TI  - [Tramadol in the vascular pains of patients with systemic scleroderma and other
      rheumatic diseases].
AB  - A study was made of the effect of tramadol on vascular pains in 20 patients with
      systemic scleroderma and other rheumatic diseases, using a visual analogue scale.
      In eleven patients, ischemic and ulceronecrotic lesions were at the basis of the
      painful syndrome. In this case the pains were most severe. In five patients, the
      lesions were of vascular and neuromuscular character. 50% of the patients
      demonstrated a good effect, 35% a satisfactory one, and 10% had a complete
      analgesia. Tramadol was administered in a daily dose of 100 to 200 mg, mainly per
      os. It is recommended that tramadol may be used in patients with the painful
      syndrome of vascular genesis.

PMID- 8146788
TI  - [Drug-induced remission in the severe progressive variant of rheumatoid
      arthritis].
AB  - Analysis of the remission incidence and duration has been made in 71 patients
      with severe progressive rheumatoid arthritis (RA) during the 10-20-year follow-up
      period, with special attention paid to the role of the disease-modifying drugs
      (DMARDs). Remission occurred only in those patients who received permanent long
      term systematic treatment with DMARDs. Such a therapeutic approach resulted in
      remission lasting from 5 to 11 years for 32% of the patients. Otherwise the
      patients who received episodic non-regular DMARDs therapy or symptomatic
      treatment with nonsteroidal anti-inflammatory drugs or steroids had no remission
      at all. A detailed analysis of the cases of remission is presented. The authors
      are of the opinion that after the disappearance of the clinical signs of RA the
      maintenance basic therapy may be continued.

PMID- 8146789
TI  - [The choice of the method for intravascular laser therapy in rheumatoid
      arthritis].
AB  - A randomized placebo-controlled study was made of the clinical efficacy of four
      different methods of intravascular laser blood irradiation (ILBI) with helium
      neon laser in 150 patients suffering from rheumatoid arthritis (RA). As to ILBI
      methods used, the most remarkable clinical effect was produced by daily
      procedures. The positive effect of ILBI was of liminal character bearing in mind
      the power range examined whereas the negative effect of irradiation was dose
      dependent. ILBI may cause an exacerbation of the inflammatory process in RA
      whatever the single dose and frequency of procedures. The best clinical effect
      with daily ILBI was attained in women, individuals with the presence of
      rheumatoid factor but with low titers thereof, and in patients with initial
      stages of RA and minimum inflammation activity. The efficacy of ILBI may be
      predicted on the basis of the patient's clinical findings.

PMID- 8146790
TI  - [The use of the results of current instrumental methods of cardiological
      examination in the sociomedical expert assessment of patients with rheumatic
      heart defects].
AB  - Altogether 103 patients with rheumatic heart disease were examined within
      different times after prosthetics of heart valves (mitral or aortal). The purpose
      was to elaborate the principles of applying the data of instrumental methods of
      cardiological examination to the improvement of disability criteria. The
      examination included echocardiography, tetrapolar chest rheography and ECG
      exercise test. The data allowed one to estimate myocardial reserves and to
      specify the intensity of functional disorders of the cardiovascular system. The
      expert medical conclusions on the working ability were revised in 47 patients,
      bearing in mind the data obtained. Before the examination 70 patients (68%) were
      considered to completely lose the working ability. However, after the examination
      their number dropped to 34 (33%), whereas the number of persons able to work rose
      from 5 to 12%.

PMID- 8146791
TI  - [The clinical manifestations of a purine metabolic disorder in the practice of
      the internist].

PMID- 8146792
TI  - [The unresolved problems of plasmapheresis].

PMID- 8146793
TI  - [The use of Allomaron in treating hyperuricemia].

PMID- 8146794
TI  - [The attitude to health problems of men: a 3-year epidemiological study of an
      unorganized population of a large industrial center in western Siberia].
AB  - The tendencies in and control of cardiovascular diseases were studied for three
      years according to the MONICA psychosocial program. A random representative
      sample of 753 men aged 25-64 years (in the first screening) and 739 men (in the
      second screening) permanently living in one of the districts of Novosibirsk were
      examined. The purpose was to investigate the knowledge of the population of the
      issues related to the health status: self-estimation of the health status,
      knowledge of blood pressure magnitude, attitude to the prophylaxis, tobacco
      smoking and changes in nutrition. The data obtained indicate that self-estimation
      of the health status changed for the worse in all the age groups. The share of
      persons asserting that they are ill or not entirely well rose by 12% and amounted
      to 62%. A decrease was recorded in the number of men not aware of the level of
      their blood pressure, namely from 27% in the first screening to 17% in the second
      screening. The number of tobacco smokers remained practically unchanged (55 and
      54%). However, the number of men who would like to change their attitude toward
      tobacco smoking increased more than 1.5-fold. The treatment of the proposals
      concerning alterations in nutrition changed for the better in persons aged 45-64
      years. On the contrary, it changed for the worse in persons aged 25-44 years.

PMID- 8146795
TI  - [The attitude of Nal'chik schoolchildren toward harmful habits].
AB  - Questionnaires were used to study the attitude of 4594 Nal'chik schoolchildren
      (86% of the representative population sample) to harmful habits to establish the
      incidence of the latter ones. 38.2% of the boys and 11.8% of the girls smoked,
      among them 24.2 and 2.7% respectively smoked on a regular basis (one cigarette a
      week). 39.5% of the boys and 25% of the girls took alcoholic drinks. This number
      did not include 11.4% of the boys and 3.6% of the girls who drank before but
      discontinued drinking completely for the last 12 months. The causes of tobacco
      smoking and alcoholization turned varied, with the main of them being a wide
      prevalence of harmful habits among the adult population and extremely low
      knowledge of a real influence exerted by tobacco-smoking and alcohol on human
      body. It is significant that about 20% of the questioned failed to give a
      conclusive answer to the items of the questionnaire. In addition to the lack of
      health education, this may lead to an increase in the spread of harmful habits
      among schoolchildren. Based on the data obtained attempts are made to carry out a
      goal-oriented work aimed at the formation of a healthy way of life among school
      children.

PMID- 8146796
TI  - [Experience and results with an approach to preventing ischemic heart disease in
      a region].
AB  - The program of coronary heart disease prevention among the population of the
      administrative district of Minsk was implemented over three years through the
      managerial, administrative and medical structures. The task team performed the
      organizational and methodological work and carried out the monitoring of the
      epidemiological situation with regard to coronary heart disease. 1537 persons
      underwent primary screening and 1112 were examined after three years. A
      statistically significant increase in the awareness of the population and doctors
      of the problems of a healthy lifestyle, improved indices of arterial hypertension
      control, a tendency toward decrease in the prevalence of arterial hypertension
      were recorded during the observation period. The behavioral risk factors could
      not be influenced.

PMID- 8146797
TI  - [The causes of death in myocardial infarct patients and the problems of medical
      care quality].

PMID- 8146798
TI  - [The epidemiology of systolic and diastolic arterial hypertension in relation to
      risk factors and education among the male population of some cities of Russia,
      the CIS nations and the Baltic states (a cooperative study)].
AB  - The prevalence of systolic and diastolic arterial hypertension (AH) was studied
      on a material of random representative samples of male population aged 20-54
      years in the cities of Moscow, Saint Petersburg [correction of Sankt-Peterburg],
      Tallinn, Kiev, Novosibirsk, Alma-Ata, Tashkent and Bishkek. AH was estimated in
      connection with risk factors (RF) from the standpoint of uni- and
      multidimensional statistical analysis. It has been established that RF (age,
      cholesterol and triglycerides concentration, overweight and alcohol use) make
      more significant contribution into the prevalence of diastolic AH whereas the
      systolic AH prevalence is largely determined only by age and education. The data
      obtained are likely to form the basis for the design of a more integral system of
      prophylaxis of cardiovascular diseases.

PMID- 8146799
TI  - [The role of a diagnostic center in improving medical care for the population].

PMID- 8146800
TI  - [Means for improving polyclinic medical care for workers in railroad
      transportation].
AB  - The paper is concerned with an organizational, structural and functional model of
      the diagnostic center (DC) in the train, developed by the authors. The DC in the
      train is a new form of mobile specialized polyclinical aid to the population
      living in the area of railway stations. The purpose of the model is to draw
      nearer high-qualified counselling and diagnostic services and prophylactic aid to
      railway workers. The DC in the train was tried and introduced into western
      Siberia railway practice. The results of DC in the train establishment are
      described as is the efficacy of the automated system of early diagnosis of
      chronic noninfectious diseases, employed under DC conditions.

PMID- 8146801
TI  - [The optimization of the captopril treatment of patients with stage-II
      hypertension at polyclinics].
AB  - To optimize captopril therapy of patients suffering from stage II essential
      hypertension under ambulant conditions, use was made of an acute medicamentous
      test with that drug. The long-term systematic therapy (for a year) was provided
      to 50 patients with positive results of the test. The long-term systematic
      captopril therapy in individually selected doses led to a decrease and
      stabilization of blood pressure, minimized subjective disease manifestations and
      improved hemodynamic characteristics. The application of the drug in moderate
      doses prevented the development of side effects that might require drug
      discontinuance.

PMID- 8146802
TI  - [Principles for the conservative treatment of obliterating arterial diseases of
      the lower extremities in outpatient practice].
AB  - Approaches to the treatment of patients suffering from chronic obliterating
      diseases of lower limb arteries under ambulant conditions are discussed. The
      authors hold that the given trend is most important for the attainment of long
      term results including those after surgical interventions on vessels. The main
      cause of insufficiently effective medical aid rendered to such patients consists,
      in the authors' opinion, in the lack of trained internists specialized in
      angiology. The results of ambulant treatment of patients with chronic
      obliterating arteriopathies are provided.

PMID- 8146803
TI  - [The determination in the polyclinic of the genetic risk for the development of
      chronic cholecystitis].
AB  - Studies into the genealogical anamnesis and a number of genetic characteristics
      of patients with chronic cholecystitis allowed one to confirm the significance of
      hereditary burden in the development of cholecystitis and to identify genetic
      markers (B(III) blood group), type Hp 1-1, HLA A3, HLA A30 and HLA B5, as well
      genetic protectors (O(I) blood group), HLA B8, HLA B14 of the disease. It has
      been established that hereditary factors play the most important role in the
      development of chronic calculous cholecystitis as compared to acalculous
      cholecystitis, which manifests itself in greater significance of hereditary
      burden and greater power of association with genetic markers of the disease.

PMID- 8146804
TI  - [The characteristics of the course of pollinosis in a heavily industrialized area
      with an ecologically unfavorable situation].

PMID- 8146805
TI  - [The rating method of evaluating the theoretical and practical training of
      students in a department of polyclinic therapy (a 2-year experience)].

PMID- 8146806
TI  - [Nephrology problems in the works of E. M. Tareev].

PMID- 8146807
TI  - [The place of rheumatic diseases in the pathology of the population of the
      Russian Federation].

PMID- 8146808
TI  - [Immune response and pathophysiology of the allergic reaction].
AB  - The allergic immune response is characterized by a number of cellular and
      molecular interactions. Allergens are taken up through the respiratory or
      digestion tract or the skin by dendritic cells, B cells or macrophages. After
      phagocytoses and processing, fragments of allergens are presented to the allergen
      specific T cells. By this process, allergen-reactive T cells are induced, which
      are predominantly of the Th2 type and which secrete the cytokines IL-4, IL-5 and
      IL-10. In contrast, during a normal immune response to bacterial or viral
      allergens, T cells of the Th1 type are induced, which produce IFN gamma and IL-2
      but not Th2 cytokines. A direct contact of Th2 cells with B cells results in
      activation of B cells. The Th2 cytokine IL-4 instructs B cells to switch from IgM
      to IgE antibody production. IgE antibodies play a central role in the induction
      of allergic diseases. IgE antibodies are taken up by basophils and mast cells by
      virtue of high-affinity receptors for IgE on these cells. Allergen confrontation
      leads to the activation of such IgE-sensitized cells, which results in the
      release of various mediators such as histamine, leukotrienes and prostaglandins;
      together, they induce the clinical manifestations of allergic reactions. Recent
      findings have shown that mast cells (and basophils) from atopic tissue are able
      to produce cytokines such as IL-4 and can thereby induce IgE antibody production.
      IL-5 generated by allergen-reactive Th2 cells attracts and activates eosinophils,
      which are responsible for tissue destruction in allergic asthma.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8146809
TI  - [Allergology in the year 2000].
AB  - As already today, the use of fully standardized allergens for specific allergen
      phenotyping will be essential also in the future. The determination of allergen
      reactive patterns in patients will be performed with panels of tracer allergens
      being produced by molecular biology techniques. Such recombinant allergen
      proteins can in principal also be used for specific immunotherapy. Undesired
      biological properties of allergens can be removed by directed mutagenesis.
      Because recombinant allergens can bind IgE only selectively, T-cell activating
      fragments thereof may be employed. This may lead to fully artificial protein
      constructs consisting of immunogenic and allergy-suppressing parts. A different
      possible way is the therapeutic use of immunologically active proteins, such as
      monoclonal antibodies or soluble receptors, which suppress IL-4 and/or IgE
      synthesis. The accessibility of these proteins will lead to a better
      understanding of the mechanisms responsible for the development of allergy. At
      the end of this development one could conceive the construction of low molecular
      chemical agents, drugs in the classical sense, able to regulate IgE synthesis. Of
      highest significance will be the establishment of genetic markers for atopy and
      allergy. Such genes may not only indicate a genetic predisposition for the
      disease but also open an immense spectrum of new diagnostic and therapeutic
      applications in allergy.

PMID- 8146810
TI  - [Allergic reactions of the respiratory tract].
AB  - Allergic rhinoconjunctivitis and allergic asthma bronchiale are immunologically
      mediated diseases of the respiratory tract. Dependent on the allergen, they occur
      seasonally or perennially. Allergens can cause a specific reaction of the immune
      system, mediated by IgE-antibodies in individuals with a genetic predisposition.
      Different mediators are released from mast cells, and complex immunopathological
      mechanisms lead to inflammatory changes of the mucosa. A significant increase of
      allergies has been observed in the last decades. Indoor and outdoor allergens can
      be differentiated. Mites and animal dander are the most important indoor
      allergens. The pollens of birch, alder, hazel, different grasses and mugwort are
      the most important outdoor allergens. For diagnostic purposes skin tests,
      laboratory analyses and provocation tests are used. The best therapy is
      elimination of the offending allergen. As pharmacological agents histamine
      receptor antagonists, topical corticosteroids and topical cromoglycate are
      currently used. Immune therapy is the most specific form of treatment.

PMID- 8146811
TI  - [Food allergy].
AB  - Food allergy (hypersensitivity) is a form of adverse food reaction in which the
      reaction is caused by an immunological response to a food. The majority of
      immediate allergic reactions to food are IgE-mediated. Although the true
      prevalence of food allergy is unknown, it is said to be higher in children than
      in adults. Data suggest that the prevalence in the general population is about
      1%. In children the most common foods eliciting an allergic reaction are cow's
      milk, eggs, fish, peanuts and soy. In adults celery, fish, nuts, peanuts and
      shrimp are the major source of food allergy. Usually, food-allergic adults are
      sensitized to pollen, e.g. in the frame of the celery-carrot-mugwort-spice
      syndrome. There is some evidence that antigenic similarity exists between pollen
      and food proteins. Clinical signs and symptoms due to food allergy are cutaneous,
      respiratory, gastrointestinal reactions such as urticaria, laryngeal edema,
      asthma or diarrhea. Food anaphylaxis is the most severe generalized and sometimes
      fatal reaction. History, physical examination, skin tests and laboratory tests
      (RAST) provide the basic tools for identifying a food allergy. However, the "gold
      standard" for diagnosing allergic food reactions is the double-blind, placebo
      controlled food challenge. The predictive accuracy of positive skin tests is less
      than 50%, as demonstrated by double-blind, placebo-controlled food challenges.
      The only proven form of management in food allergy is strict elimination of the
      offending food. Food-allergic individuals must be provided with an emergency kit
      containing an oral antihistamine of the second generation and a
      corticosteroid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146812
TI  - [Atopic dermatitis].
AB  - Atopic dermatitis (AD) is a multifactorial skin disease with a chronic or a
      chronic-relapsing course which often starts during infancy. The persistence rate
      of AD after the puberty is certainly higher than mostly assumed. 60% of the
      patients also develop respiratory atopies as hay fever or bronchial asthma. The
      etiology of this distressing skin condition is still obscure, but an
      immunological disturbance of the T-cell immune response is most probably
      implicated in its pathogenesis. The demonstration of IgE-bearing epidermal
      Langerhans cells with high-affinity receptors for IgE opens up new perspectives
      in its pathophysiology. As no efficient treatment of AD is known and a
      symptomatic treatment, local with emolients, corticosteroids and/or disinfectants
      as well as internal with antihistamines, is often difficult and unsatisfactory,
      prevention is of particular importance. The efficacy of prolonged breast-feeding,
      a strict prohibition of cow milk, egg, fish--during the first six months of life-
      and of keeping pets as well as a consequent treatment against house-dust mites
      can reduce the incidence of AD in 'at risk' children with a family history of
      atopy. Besides symptomatic treatment a substitution of essential fatty acids, a
      UV therapy and a climate therapy are other possible approaches in the management
      of such patients.

PMID- 8146813
TI  - [Drug allergy].
AB  - Drug allergies can cause a great variety of symptoms and can thus imitate various
      diseases, like in previous times the lues. Drug allergies can be classified into
      three subgroups, which differ in their pathophysiology and require different
      diagnostic steps: firstly, classical drug allergies which are directed to the
      drug itself, a reactive compound of it or some contamination of the drug;
      secondly, pseudoallergic reactions which are caused by nonimmune mediated
      degranulation of mast cells and basophils; and thirdly, autoimmune reactions in
      which the drug elicits an immune reaction to autologous structures. A very
      detailed (criminalistic) history has the highest priority for the clarification
      of a suspected drug-allergic reaction; in addition, skin tests, serological tests
      and the lymphocyte transformation test might be useful. One should differentiate
      between tests which imitate the drug-elicited allergic reaction (i.e. Coombs test
      in drug induced hemolytic anemia) and tests which solely indicate a
      sensitization, these tests should be interpreted accordingly.

PMID- 8146814
TI  - [Prevention of exposure in respiratory allergies].
AB  - Sensitization to indoor allergens like house-dust mite and animal dander as well
      as outdoor allergens like grass and tree pollen play an important role in the
      development to atopic airway disease, i.e. atopic rhinitis and conjunctivitis and
      allergic asthma. Studies on emergency room patients in the US showed that the
      sensitization to cat dander and house-dust mite Dermatophagoides represented risk
      factors for acute attacks of asthma. However, irrespective of the inheritance of
      atopy, disease of specific organs and expression of symptoms remain highly
      variable and are likely to depend on a multiplicity of environmental factors, the
      most important of which is likely to be the level of exposure to the sensitizing
      allergen. There is increasing evidence that exposure to potential allergens early
      in life is important. Concentrations and timing of the exposure seem fundamental.
      The elimination of allergens in households of atopic individuals is crucial in a
      prophylaxis and therapy. There have been several publications on mite allergen
      elimination procedures; a lot of them are uncontrolled, and allergen reduction is
      not significant. This article tries to compare trials reporting of improvement of
      clinical symptoms and significant reduction of indoor allergens with those trials
      which did not achieve significant results.

PMID- 8146815
TI  - [Decision making in diagnosis and therapy].

PMID- 8146816
TI  - [Allergology general practice in Switzerland: present and future].
AB  - The conditions of an allergological evaluation was determined in Switzerland,
      based on a questionnaire (1535 physicians and 648 pharmacists, of whom 33%
      answered). Besides dermatologists and allergists, ENT specialists are most
      frequently confronted with allergological problems. Serological determination of
      IgE are performed more frequently than skin tests, specifically by specialists
      for internal medicine and paediatrics. Pharmacists are quite often asked for
      remedies and tend to use alternative medical approaches more frequently than
      physicians. The data show that the specialty of allergology is changing and that,
      along with the high frequency of allergological patients, many non-allergologists
      participate in their treatment. The allergist of the future will deal more with
      complicated cases and be on the front line for establishing new diagnostic tools
      and therapies.

PMID- 8146817
TI  - [Risk related to withdrawal from non-psychotropic drugs].
AB  - A review of the available literature concerning sudden withdrawal of drugs shows
      that withdrawal syndrome have occurred with centrally antihypertensive drugs,
      beta-blockers on anginal patients, antiparkinsonian drugs and glucocorticoids.
      Because of a lack of controlled trials led among a large number of individuals,
      the correct frequency of this withdrawal syndrome is unknown. In most patients,
      it's hard to distinguish a return to a previous state from an overshoot
      phenomenon. In that way, gradual and supervised withdrawal of these agents should
      prevent the complication of sudden cessation of these therapy.

PMID- 8146818
TI  - [Mechanism of receptor regulation during repeated administration of drugs].
AB  - The effects of drugs is mainly explained by their action on specific receptors
      located on target cells. However, the receptors are can be regulated by changes
      into the levels of the physiological neurotransmitter and/or by drugs. A chronic
      treatment by an agonist induces a desensitization leading to a decrease in
      cellular response. The desensitization is "homologous" when it only involves the
      activated pathway and "heterologous" when a decrease in the response to other
      factors (transmitters, drugs) appears. At the molecular level, desensitization is
      explained by covalent modification of the receptors by phosphorylation catalyzed
      by a variety of protein kinases. A long term stimulation elicits an
      internalization of the receptor followed by degradation: this mechanism is called
      "down regulation". In contrast, treatment with antagonists can induce
      hypersensitization (i.e. increase in the cellular response) with up regulation.
      The consequences of these notions are discussed in term of both clinical
      pharmacology and pharmacovigilance.

PMID- 8146819
TI  - Drug withdrawal. Natural drug adaptation, & the assessment, prevention and
      management of drug withdrawal.

PMID- 8146820
TI  - [Physiological bases of undesirable effects of drugs on sexuality].

PMID- 8146821
TI  - Animal models for sexual behavior.

PMID- 8146822
TI  - [Value of autoquestionnaires in the evaluation of sex disorders related to
      drugs].
AB  - Symptoms can be assessed by the subject or the patient himself. Drug-related
      sexual dysfunction may be of clinical relevance for medication compliance. Three
      kinds of self-rating scales are available: yes/no questionnaire, multiple choice
      questionnaire and visual analogue scales. Self-rating can be absolute (intensity
      score) or relative (improving or worsening score), over last rating or over
      baseline. Self-rating necessarily implies: comprehension of the vocabulary and
      the instructions by the subject; cooperation of the subject; and careful checking
      of the answers by the clinician. Main metrologic qualities are sensitivity,
      reliability and validity. To assess changes in sexual function, the "golden"
      sexual function questionnaire does not seem to exist. Separate questionnaires are
      provided for men and women with appropriate changes for specific items. The
      number of questions varies from 4 to 20 even more. Several aspects of the male
      and female sexuality must be studied. Two main questions can be raised: 1) is
      there any relation between responses obtained with self-reported questionnaire
      and responses to questioning by a clinician? is there any relation between self
      reported sexual dysfunction and objective measures of sexual function like
      plethysmography?

PMID- 8146823
TI  - Methodological problems in the evaluation of drug induced sexual dysfunction for
      oral contraceptives.

PMID- 8146824
TI  - Sexual dysfunction as a suspected drug reaction reported to WHO Collaborating
      Centre for International Drug Monitoring.

PMID- 8146825
TI  - [Impact of therapeutics on sex. Value of measurements of quality of life].
AB  - Quality of Life is a new clinical dimension with the objective of evaluating the
      impact of a disease or of a treatment on patients well being. Quality of life is
      a measure of increasing interest. It is a global and cumulative measure, relevant
      for the evaluation of the therapeutic benefit of a treatment. It can be measured
      through "specific" or "generic" tools. Very few experimental literature exploring
      the impact of pathologies over the sexual sphere exists today. Only generic
      scales have been used, because no specific scale has been developed up to now.
      The impact of certain pathologies such as depression or diabetes has been
      documented, but very little objective information exists concerning the sexual
      repercussion of the chronic use of drugs (anti depressive, anxiolytics). Sexual
      quality or life as a risk factor for disease development is also dimension that
      has been explored, but only superficially. In a general way, no evidence exists
      concerning a reel correlation link between pathologies, treatments and sexual
      quality of life and this specific dimension of the quality of life still remains
      to be explored further.

PMID- 8146826
TI  - [The Swiss Centre of Pharmacovigilance].
AB  - The Swiss Drug Monitoring Center SANZ operates the spontaneous reporting system
      in Switzerland and is a private institution founded and funded by the societies
      of the Swiss health professionals and the Swiss pharmaceutical industries. The
      goal of SANZ is to collect and evaluate ADRs and thus to create signals. In 1991
      SANZ received 792 reports. SANZ informs the health professionals periodically on
      drug safety problems. Reports on serious ADRs are exchanged with the regulatory
      authorities.

PMID- 8146827
TI  - [Evaluation of unexpected and toxic effects of omeprazole (Mopral) reported to
      the regional centers of pharmacovigilance during the first 22 postmarketing
      months].
AB  - Omeprazole has been marketed in France since 1989, for the healing of peptic
      ulcers, erosive reflux esophagitis and the Zollinger Ellison syndrome. It is a
      proton pump inhibitor which inhibits the acid secretion in the stomach. In the
      majority of the clinical trials, omeprazole has been found to be well tolerated:
      headache, dizziness, skin rash, constipation have just been noted. Since
      September 1989, 143 adverse reactions have been reported to pharmacovigilance
      centres and Astra France: 37 neurological and psychiatric side effects,
      especially confusion in patients with hepatic diseases and/or advanced age; 35
      cutaneous reactions, generally rash and urticaria; 22 hematological effects:
      leucopenia and agranulocytosis have been reported but the relation with
      omeprazole is very uncertain; 10 gastrointestinal effects, generally diarrhoea,
      nausea, vomiting and abdominal pain; 8 hepatic disorders, especially moderate
      elevation of aminotransferases. This study confirms the safety of this drug,
      during short treatment; the frequency of notified adverse effects is about 1/12
      200 treatments of 4 weeks. The ministry of health, has decided, in november 1991,
      to inform the prescribers of this potential toxicity of omeprazole, particularly,
      of the risk of confusion, hepatotoxicity and leucopenia.

PMID- 8146828
TI  - [Users of a regional center of pharmacovigilance].
AB  - We analyzed the users of the Bordeaux Regional Centre--defined as any person
      calling the Centre for an inquiry--between 1986 and 1991. During this 6-year
      period, 3,046 different users called our Centre. Among them, 2,578 (85%) called
      the Centre for the first time during this period and among them, more than 700
      became regular users. The Bordeaux Centre works in regular cooperation with
      approximately 1,200 health professionals. This corresponds to the surveillance of
      500,000 inhabitants.

PMID- 8146829
TI  - CART and logistic regression analyses of risk factors for first dose hypotension
      by an ACE-inhibitor.
AB  - Angiotensin converting enzyme inhibitors (ACEI) are established drugs for the
      treatment of congestive heart failure. Cases of symptomatic hypotension,
      especially on the first day of treatment, have been reported occasionally. The
      database we analysed consisted of 1,177 patients, mean age approximately 70 yrs,
      with congestive heart failure NYHA functional class II or III. These patients
      were treated and observed prospectively according to a uniform protocol, starting
      therapy with 2.5 mg enalapril and measuring blood pressure at hourly intervals
      for eight hours thereafter. 94.6% of the patients experienced no symptomatic
      hypotension, 4.75% moderate symptoms (e.g. dizziness, headache) and 0.59% severe
      symptoms (e.g. fainting, collapse, renal failure). For the analyses of risk
      factors a large number of baseline variables were analysed univariately to select
      those significant for inclusion in a multivariate stepwise logistic regression.
      Alternatively the CART-(classification and regression tree) technique was used.
      Both techniques showed diastolic blood pressure < or = 70 mmHg to be the single
      most significant risk factor. CART-analyses showed also pretreatment with
      nitrates and systolic blood pressure < or = 120 mmHg to be of prognostic
      relevance. Thus CART is a valuable complement when looking for prognostic
      factors.

PMID- 8146830
TI  - [Fetal surveillance after administration of gynecological ovules and tablets
      during pregnancy. Apropos of 168 treated pregnant women].

PMID- 8146831
TI  - [Allergy to drug-coloring agents. Comparison of reported cases and the experience
      of the Regional Center of Pharmacovigilance].

PMID- 8146832
TI  - [Tiopronin (Acadione) and interstitial pneumonia].

PMID- 8146833
TI  - [Rhabdomyolysis related to ingestion of pravastatin (Vasten)].

PMID- 8146834
TI  - [Severe hyponatremia caused by inappropriate antidiuretic hormone secretion
      syndrome induced by fluoxetine].

PMID- 8146835
TI  - [Fulminating necrotizing fasciitis after intramuscular injection of a corticoid.
      Contributing role of non-steroidal anti-inflammatory agents].

PMID- 8146836
TI  - [Thrombopenia caused by isoniazid].

PMID- 8146837
TI  - [Repeated thromboses during treatment with carbamazepine].

PMID- 8146838
TI  - [Does a metabolic interaction exist between viloxazine and antivitamins K?].

PMID- 8146839
TI  - [Case reports on drug-induced chronic diarrhea. An often unrecognized etiology?].

PMID- 8146840
TI  - [Sexologists and side-effects of drugs].

PMID- 8146841
TI  - [Severe hypercalcemia. Value of clodronate (Clastoban) in chronic renal
      insufficiency and hemodialysis. Apropos of 3 cases].

PMID- 8146842
TI  - [Risks related to the resorption of a glycine-based irrigation solution. 10 cases
      reported to the Poison Control Center and the Regional Center of
      Pharmacovigilance of Paris-Fernand-Widal].

PMID- 8146843
TI  - [Acute percutaneous poisoning with boric acid solution].

PMID- 8146844
TI  - [Immunoallergological studies in toxic skin eruptions caused by diltiazem
      (Tildiem 300 LP)].

PMID- 8146845
TI  - [Hypocoagulation caused by thiabendazole-acenocoumarol interaction].

PMID- 8146846
TI  - [Drug consumption in Angiers (Algeria) according to a survey of families].
AB  - A sampling survey was carried out in Algiers with the aim of improving
      epidemiological understanding of drug consumption. By a direct face-to-face
      interviewing, 936 households were surveyed, i.e. 7,217 individuals. The overall
      prevalence of regular drug consumption was 104.3%. The one of drug consumption
      during the month prior to the survey was 92.1%. Subjects aged 65 years and older
      had the highest prevalence (37.6%) of regular consumption; the most frequently
      consumed drugs were then antihypertensive agents accounted for 19.1% of all drugs
      used. The most frequently consumed drugs by children under age 15 years were
      antimicrobials accounted for 41.2% of total drug use. Women were more likely to
      use drugs than men. There was an association between social class and drug
      consumption; the lower the social class of individuals, the lower their
      consumption. The household surveys seem to be an interesting source of data on
      drug use.

PMID- 8146847
TI  - [A one-year prospective and intensive pharmacovigilance of antilipemic drugs in
      an hospital consultation for prevention of risk factors].
AB  - Cholesterol-lowering drugs include three major pharmacological classes: a)
      fibrates, b) statines, HMG-CoA reductase inhibitors and c) cholestyramine. The
      late eighties were characterized by the introduction of HMG-CoA reductase
      inhibitors in therapeutics. For 12 months (1st January-31 December 1991), a
      prospective intensive program of pharmacovigilance investigated the occurrence of
      side effects among the three pharmacological classes of cholesterol-lowering
      drugs in a specialized unit for prevention of atherosclerosis and dyslipidemia.
      Among 3,506 out patients who received cholesterol-lowering drugs, 36 side effects
      were reported (i.e. 1 side effect for 98 out-patients). Most of the side effects
      were observed with statines (61%). The most frequently observed side effects were
      gastralgia (19.5%) observed with the three classes of drugs and hepatitis with
      HMG-CoA reductase inhibitors (8.5%) or fibrates (3%) whereas myopathy (12%) only
      occurred with statines. The other side effects were cutaneous (14%: eczema, skin
      rashes) or neuropsychiatric (11%: insomnia...) ones. This study emphasizes the
      low frequency of severe side effects (myopathy: 1 per 1,000 prescriptions,
      hepatitis: 1 per 1,000 prescriptions) with cholesterol-lowering drugs in current
      practice.

PMID- 8146848
TI  - [Hyponatremia caused by inappropriate antidiuretic hormone secretion syndrome
      during treatment with fluoxetine].

PMID- 8146849
TI  - [Hyperprolactinemia induced by domperidone].

PMID- 8146850
TI  - [Severe acute neuropathy caused by vincristine. A new case].

PMID- 8146851
TI  - [Psychomimetic syndrome induced by nalbuphine].

PMID- 8146852
TI  - [Drug-induced esophageal ulcer. Apropos of a new case].

PMID- 8146853
TI  - [Aseptic meningitis caused by ibuprofen (Nurofen) in connective tissue diseases].

PMID- 8146854
TI  - [Thrombopenic purpura under preventive treatment with enoxaparin].

PMID- 8146855
TI  - [Severe hyponatremia after repeated administration of terlipressin].

PMID- 8146856
TI  - [Cardiorespiratory arrest after injection of Trombovar (sodium tetradecyl
      sulfate)].

PMID- 8146857
TI  - The MLC assay as a test for HLA-D region compatibility between patients and
      unrelated donors: results of a national marrow donor program involving multiple
      centers.
AB  - Mixed lymphocyte culture (MLC) assays from 763 patients and prospective unrelated
      marrow transplant donors identified through the National Marrow Donor Program
      (NMDP) were analyzed for their overall utility in measuring HLA-D region
      compatibility. The assays were performed at 31 different transplant centers
      (range, 1 to 197; median, 9 assays per center). A total of 325/763 (42.6%) of the
      tests were judged to be uninterpretable, either due to lack of sufficient control
      cells included in the assay (89 tests) or to insufficient reactivity by patient
      and/or donor cells (236 tests). Among the 438 tests that could be interpreted,
      HLA-Dw phenotyping with HLA-D homozygous cells was performed for a subset of 190.
      The relative response (RR) values from these 190 tests, however, were not clearly
      separable into distinct populations; i.e., RR values corresponding to Dw identity
      versus nonidentity between patient and donor could not be reliably discriminated.
      The predictive value of a nonreactive MLC for Dw identity was calculated to be
      0.91 for RRs of < or = 20%, while the predictive value of a reactive MLC for Dw
      nonidentity was 0.35 for RRs of > 20%. These results, based on an analysis of
      data submitted from multiple transplant centers testing patients who had a
      variety of hematologic disorders, suggest that the MLC assay is a relatively
      imprecise method for determining HLA-D region compatibility between patient and
      prospective unrelated marrow donor.

PMID- 8146858
TI  - Large-scale oligonucleotide typing for HLA-DRB1/3/4 and HLA-DQB1 is highly
      accurate, specific, and reliable.
AB  - DNA typing of HLA class II alleles of the DRB1/3/4 and DQB1 loci using sequence
      specific oligonucleotide probes and polymerase chain reaction-amplified DNA was
      used for the large-scale typing of donors for the National Marrow Donor Program
      unrelated donor registry. The results of quality control analysis for the first 7
      months of the project show the typing to be highly accurate, specific, and
      reliable. The percent of correctly classified HLA oligotypes based on 1652 DRB1
      and 1652 DQB1 assignments was greater than 99% for DRB1/DRB3/DRB4 and greater
      than 98% for DQB1. This level of accuracy is particularly remarkable because the
      quality control samples could not be distinguished from 9011 donor samples tested
      at the same time by the laboratories.

PMID- 8146859
TI  - HLA-B locus DNA typing: detection of B*7801 and seven additional alleles by BW6
      specific exon 2 amplification.
AB  - A molecular approach to type a new HLA-B5 antigen, HLA-BSNA, characterized by its
      unusual association with the public determinant BW6, referred to as B*7801, has
      been designed. Antigens disclosing serological identity with SNA, BX1 and Te76
      were also investigated. Based upon HLA-B exon 2 group-specific PCR, the following
      procedure was established: 5' and 3' primers were designed by targetting the
      codons 11-12 (AM) and 81-83 (LRG), respectively, in exon 2 (alpha 1 domain). The
      5' primer discriminates with HLA-A, -C genes and pseudogenes, while the 3' primer
      detects the sequence encoding the BW6 epitope (NLRG) and discriminates it from
      the BW4 epitope. The combination of this pair of primers specifically amplifies
      26 HLA-B alleles. Oligotyping for B*7801 was performed using a combination of two
      non-radioactively labeled SSO probes identifying positions T45 and D74 in exon 2.
      To resolve ambiguous hybridization patterns, an additional set of probes was
      used. The specificity of this BW6-group-specific amplification procedure was
      investigated on 150 genomic DNA samples. Among them, we obtained 94 amplified DNA
      products which were tested with eight SSOs. Beside B*7801, the following B
      alleles could be defined: B*0801, B*35, B*5401, B*5501-2, B*5601-2, B*1501-7
      (including B62, B75 and B72) and B*4601. SNA, BX1 and Te76 DNA samples gave
      similar hybridization pattern providing a clue to the identity of these antigens.
      This "one PCR and two probes" procedure represents a simple oligotyping strategy
      which can also be applied to type many other HLA-B specificities.

PMID- 8146860
TI  - Widespread tissue distribution of aminopeptidase A, an evolutionarily conserved
      ectoenzyme recognized by the BP-1 antibody.
AB  - Early B-lineage cells in mice express a cell surface glycoprotein, recognized by
      the BP-1 and 6C3 monoclonal antibodies, that has been identified as
      aminopeptidase A (APA E.C.3.4.11.7). In the present studies we obtained evidence
      by DNA "zoo-blot" analysis that the APA gene is highly conserved. This ectoenzyme
      catalyzes the removal of N-terminal Glu- and Asp-residues to convert angiotensin
      II to angiotensin III, a degradation step important in local regulation of blood
      pressure in mammals. To gain further insight into the physiology of this
      molecule, which is shared between immune and vascular systems, we examined the
      tissue distribution of BP-1 mRNA using a cDNA probe and of the protein antigen
      using the BP-1 antibody for immunohistology. APA transcripts were present in all
      tissues examined. Abundant BP-1/APA was found in the intestinal brush border of
      the small intestine, renal glomeruli, proximal renal tubules, pulmonary alveolar
      walls and vascular endothelium in many organs. Other tissues containing the BP-1
      antigen included stromal cells in the thymus cortex, bile canaliculi in liver,
      gall bladder epithelium, interlobular ducts in pancreas, the ovarian theca
      interna, basement membrane of the epididymis and the splanchnopleure in placenta.
      APA enzyme activities have been identified in most of these locations, in keeping
      with identification of the BP-1/6C3 antigen as APA. The data suggest this
      ectopeptidase may serve diverse physiologic roles in a broad spectrum of tissues.

PMID- 8146861
TI  - Structural heterogeneity in HLA-B70, a high-frequency antigen of black
      populations.
AB  - Although the B70 antigen exhibits allele frequencies of 8-23% in African and
      American black populations, it remains poorly defined. Cloning and sequencing of
      cDNA encoding B70 antigens from six cell lines has identified a group of three
      closely related alleles: B*1503, B*1509 and B*1510, that form a subgroup of the
      B15 family. The sequences of these alleles and, in particular, B*1503, are close
      to that of the HLA-B consensus consistent with the difficulty in their
      serological definition. The products of the three alleles correspond to three
      electrophoretically detected variants of the B70 antigen and some correlation
      with the B71 and B72 subspecificities of the B70 antigen can be made. A fourth
      allele, B*7901, previously described by Choo et al. (J. Immunol. 147: 174-180,
      1991) that was not serologically typed as B70, differs by a single nucleotide
      substitution from B*1510. The sensitivity of alloantibodies to single differences
      in peptide binding residues suggest a role for bound peptides in the HLA-B70
      alloantigenic specificities. The heavy chains encoded by the four alleles differ
      at four peptide binding residues of the antigen recognition site, the
      evolutionary modification of which can be explained in terms of interallelic
      recombination events.

PMID- 8146862
TI  - HLA-A*8001 is a member of a newly discovered ancient family of HLA-A alleles.
AB  - A member of a new HLA-A locus family, HLA-A*8001, has been characterized from 3
      African-American individuals expressing a unique HLA-A serologic specificity. The
      HLA-A*8001 sequence is most closely related to alleles of the HLA-A1/3/11 family,
      although it also contains residues characteristic of the HLA-A2/28, -A9, -A10,
      and -A19 families. More importantly, the HLA-A*8001 sequence contains four unique
      nonsynonymous (amino acid replacing) nucleotide substitutions absent from all
      other primate A locus alleles. In addition, five other nucleotide substitutions,
      four nonsynonymous and one synonymous (silent), observed only in non-human
      primate A locus alleles were found. Neighbor-joining tree analysis of HLA-A*8001
      supports the notion that the HLA-A*8001 allele is a member of a new HLA-A locus
      family which was derived from the ancestral A3 lineage but diverged early in the
      evolution of the HLA-A locus.

PMID- 8146863
TI  - Complete nucleotide sequence of MHC class I alleles in the HT29 colon cancer cell
      line.

PMID- 8146864
TI  - HLA-DRB1 first domain sequences of two new DR11 alleles and one novel DR4 allele.

PMID- 8146865
TI  - Characterization of a novel DQB1 (DQB1*0609) allele by PCR amplification with
      sequence-specific primers (PCR-SSP) and nucleotide sequencing.

PMID- 8146866
TI  - Clinical symptomatology and management of mushroom poisoning.
AB  - Among poisonous mushrooms, a small number may cause serious intoxication and even
      fatalities in man. Humans may become symptomatic after a mushroom meal for rather
      different reasons: (1) ingestion of mushrooms containing toxins, (2) large
      amounts of mushrooms may be hard to digest, (3) immunological reactions to
      mushroom-derived antigens, (4) ingestion of mushrooms causing ethanol
      intolerance, and (5) vegetative symptoms may occur whenever a patient realizes
      that there might be a possibility of ingestion of a toxic mushroom after a
      mushroom meal. Based on the classes of toxins and their clinical symptoms, seven
      different types of mushroom poisoning can be distinguished: (1) phalloides, (2)
      orellanus, (3) gyromitra, (4) muscarine, (5) pantherina, (6) psilocybin, and (7)
      gastrointestinal mushroom syndrome. Two other entities of adverse reactions to
      mushrooms are (8) coprinus and (9) paxillus syndrome. Phalloides, orellanus,
      gyromitra and paxillus syndrome may lead to serious poisoning, which generally
      requires treatment of the patient in an intensive care unit. Diagnosis of
      mushroom poisoning is primarily based on anamnestic data, identification of
      mushrooms from leftovers of the mushroom meal, spore analysis, and/or chemical
      analysis. Therapeutic strategies include primary detoxification by induced
      emesis, gastric lavage and activated charcoal, secondary detoxification,
      symptomatic treatment and rarely specific antidotes. Owing to progressing
      fulminant hepatic failure, lethality associated with phalloides syndrome is still
      high (5-20%). Basic treatment includes administration of silibinin and penicillin
      G, although controlled studies on its therapeutic efficacy are still lacking. In
      serious phalloides syndrome, orthotopic liver transplantation has to be
      considered. Fortunately, the prognosis in most other mushroom poisonings is
      excellent.

PMID- 8146867
TI  - Identification and characterization of hydrophobic microcystins in Canadian
      freshwater cyanobacteria.
AB  - Hepatotoxic microcystins produced by cyanobacteria in freshwater lakes represent
      a significant health hazard to humans and agricultural livestock. Liquid
      chromatography (LC)-linked protein phosphatase (PPase) bioassay analysis of
      blooms of Microcystis aeruginosa produced in a Canadian drinking water lake
      identified several PPase inhibitors with significantly greater hydrophobicity
      than microcystin-LR, based on their retention time on C18 reverse phase LC
      columns. Seven PPase inhibitors were purified to homogeneity by bioassay-guided
      fractionation involving Sephadex LH-20 chromatography and two-step reverse phase
      at pH 6.5 and 2.0. One of the PPase inhibitors, isolated in a final yield of 1.5
      micrograms/g lyophilized cyanobacteria, was identified as microcystin-LL by amino
      acid analysis and mass spectrometry. A further PPase inhibitor (20 ng/g
      cyanobacteria) was identified as microcystin-LL but with D-Ala replaced by an
      unknown amino acid. Four PPase inhibitors (< 20 ng/g cyanobacteria) were
      characterized by amino acid analysis and identified as microcystin-LV, -LM, -LF
      and -LZ (where Z represents an unknown hydrophobic amino acid). A further
      microcystin was also identified (< 10 ng/g cyanobacteria) in which arginine was
      apparently absent. The biological activity of the seven microcystins as
      inhibitors of the catalytic subunit of protein phosphatase-1 (PP-1c) was compared
      with microcystin-LR and motuporin (a hydrophobic analogue of nodularin). All of
      the compounds inhibited PP-1c with IC50 values of 0.06-0.4 nM, consistent with
      their identification as microcystins. These findings further demonstrate the
      applicability of a sensitive PPase bioassay for the identification of variant
      microcystins in the natural environment.

PMID- 8146868
TI  - Lipoxygenase-derived mediators may be involved in in vivo neutrophil migration
      induced by Bothrops erythromelas and Bothrops alternatus venoms.
AB  - Bothrops erythromelas (BEV) and B. alternatus (BAV) venoms induced a dose
      dependent neutrophil migration when injected into rat peritoneal cavities (20-160
      micrograms/cavity). These venoms (80 micrograms/rat) also induced neutrophil
      migration in the air pouch model of inflammation. This migratory response seemed
      to be related to the phospholipase A2 (PLA2) activity of the venoms. BAV had
      approximately two times more PLA2 activity than BEV, and the neutrophil migration
      induced by the former venom was two to three-fold greater than that observed with
      the latter. Heated (90 degrees C for 5 min) BEV lost about 50% of its PLA2
      activity and this was accompanied by a corresponding loss in the ability to
      induce neutrophil chemotaxis. Dexamethasone (0.5 mg/kg, s.c.), an indirect
      inhibitor of PLA2 activity, also abolished the neutrophil migration induced by
      both venoms. Since NDGA (100 mg/kg, s.c.) and dexamethasone, but not indomethacin
      (2 mg/kg, s.c.), strongly reduced the neutrophil migration induced by both
      bothropic venoms, it is suggested that arachidonate-derived lipoxygenase
      metabolites such as leukotriene B4 act as the chemotactic mediators. Macrophages
      could be the main cellular source of such metabolites since they are the
      predominant resident cells in the rat air pouch, and the migratory response of
      BEV and BAV into peritoneal cavities was potentiated in rats pretreated with
      thioglycollate. The neutrophil migration induced by BEV and BAV was not due to
      endotoxin contamination since heated BEV showed no effect and polymyxin B-treated
      BAV still remained active.

PMID- 8146869
TI  - Presence of serotonin in the venom of Conus imperialis.
AB  - The bioactive components in the venoms of cone snails are largely small peptides
      which target to a diverse set of ion channels and neuronal receptors. We report
      here the presence of substantial levels of serotonin in the venom of the imperial
      cone snail, Conus imperialis. This venom also contains many small bioactive
      peptides. The identification of serotonin has been confirmed by mass
      spectroscopy, NMR, HPLC mobility and UV spectroscopy. Although serotonin has been
      reported in arthropod venoms, it was previously reported to be absent in Conus
      venoms. We examined a total of fourteen different Conus species, and found
      detectable serotonin only in the venom of C. imperialis. Conus imperialis
      specializes in feeding upon the amphinomid polychaete Eurythoe complanata. We
      speculate that serotonin may play a role in the capture of this prey.

PMID- 8146870
TI  - Purification and partial characterization of two cytolysins from a tropical sea
      anemone, Heteractis magnifica.
AB  - Two cytolysins, designated as magnificalysins I and II, were purified from a
      tropical sea anemone, Heteractis magnifica (formerly Radianthus ritteri). The
      purification steps involved Sephadex G-50 and CM-Sepharose chromatography
      followed by Mono S and Phenyl-Superose Fast Protein Liquid Chromatography. The
      relative mol. wt of magnificalysins I and II, determined by SDS-PAGE, was
      approximately 19,000, while their isoelectric points, determined by isoelectric
      focusing in immobilized pH gradients, were 9.4 and 10.0, respectively. Those
      toxins were found to have haemolytic and lethal activities. The haemolytic
      activities of magnificalysins I and II were 3.6 x 10(4) HU/mg and 3.3 x 10(4)
      HU/mg, while their LD50 (i.v., mice) values were approximately 0.14 microgram/g
      and 0.32 microgram/g, respectively. The amino acid composition and N-terminal
      sequences of magnificalysins I and II were also obtained. They do not possess any
      cysteine or cystine residue, but are rich in basic and hydrophobic amino acids.
      The N-terminal amino acid sequences of magnificalysins I and II are
      ALAGTIIAGASLTFKILDEV and SAALAGTIIDGASLGFDILNKV, respectively. These are highly
      homologous to cytolysins from other sea anemones, particularly cytolysin III from
      Stichodactyla helianthus, a Caribbean anemone.

PMID- 8146871
TI  - Toxicology of a bovine paraplegic syndrome.
AB  - A clinical entity named 'bovine paraplegic syndrome' ('sindrome paraplejico de
      los bovinos') has spread alarmingly in the cattle-growing areas of the central
      and eastern plains of Venezuela. It is estimated that four million cattle are
      bred in the area where the disease occurs. The mortality ranges from 5 to 25% of
      the animals at risk, mostly pregnant or lactating cows. The principal
      characteristic of the bovine paraplegic syndrome is ventral or sternal decubitus,
      in animals that make vain efforts to stand when stimulated. The diagnosis is
      established when all other possible causes (e.g. paralytic rabies, botulism and
      blood parasites such as Anaplasma marginal, Babesia bovis, B. bigemina, and
      Trypanosoma vivax) have been ruled out clinically and by laboratory tests. Death
      always occurs, usually after a few days, and there is no known treatment. In this
      work, we describe results that show the presence of a toxin in the cattle
      suffering from, or liable to suffer from the syndrome. The toxin is produced by
      ruminal bacteria. In squid giant axons under voltage clamp conditions, the toxin
      blocks the sodium current. We detected the toxin analytically by absorbance
      measurements at 340 nm after reacting with picrylsulfonic acid. We obtained a
      good separation of the toxin with isocratic high pressure liquid chromatography,
      using 40% methanol in water on phenylborasil columns.

PMID- 8146872
TI  - Characterization of ruminal bacteria producing a toxin associated with a bovine
      paraplegic syndrome.
AB  - We studied the ruminal population densities of bacteria in animals with and
      without bovine paraplegic syndrome (BPS). All bacterial counts were performed
      under strict anaerobiosis. Although the rumen bacterial density was around 10(9)
      bacteria/ml in animals, both apparently healthy or suffering from BPS, a shift
      towards Gram-negative strains occurred in animals with BPS. The toxin added to
      the cultures stimulated bacterial growth. Bacterial strains from the rumen could
      produce the toxin in vitro. Gram-positive bacteria differed in their ability to
      produce the toxin; Streptomyces bovis did not produce the toxin, while
      Lactobacillus vitulinum was an efficient producer. All Gram-negative bacteria
      tested could produce the compound.

PMID- 8146873
TI  - Purification and partial characterization of a haemorrhagin (VRH-1) from Vipera
      russelli russelli venom.
AB  - A haemorrhagic toxin (VRH-1) has been purified to homogeneity from Vipera
      russelli russelli venom by subjecting it to chromatography twice successively on
      CM-Sephadex C-50. It is a protein of mol. wt 22,000 and contains one mole of
      Mg2+. Intradermal administration of this haemorrhagin in mice resulted in severe
      lung haemorrhage but produced little haemorrhage in skin. This apparent organ
      preference led us to develop a new haemorrhage assay method utilizing dye
      diffusion from lung in vitro. Proteolytic activity of VRH-1 was demonstrated
      using dimethylcasein as substrate following quantitation by reaction with
      trinitrobenzoyl sulfonic acid. Both haemorrhagic and proteolytic activities of
      VRH-1 were inhibited by serine protease inhibitors like phenylmethyl sulfonyl
      fluoride and chymostatin, but metal chelators had no effect. Lung haemorrhage is
      unlikely to be a direct reflection of a high local concentration of VRH-1. The
      administration of supernatant generated by incubation of chopped liver from
      untreated mouse and VRH-1 (in subhaemorrhagic dose) results in severe lung
      haemorrhage. This raises the possibility that VRH-1 leads to the formation of
      intermediate(s) which causes the haemorrhage.

PMID- 8146874
TI  - Affinity chromatographic purification of tetrodotoxin by use of tetrodotoxin
      binding high molecular weight substances in the body fluid of shore crab
      (Hemigrapsus sanguineus) as ligands.
AB  - A purification method for tetrodotoxin (TTX), based on affinity chromatography
      using the TTX-binding high mol. wt substances in the body fluid of shore crab
      (Hemigrapsus sanguineus) as ligands, was developed. This method was particularly
      useful for analysis of TTX in biological samples with low concentrations of TTX.
      The affinity gel prepared was highly specific for TTX, having no ability to bind
      4-epi-TTX and anhydro-TTX as well as saxitoxin.

PMID- 8146875
TI  - Toxicity of scorpion (Buthus tamulus) venom in mammals is influenced by the age
      and species.
AB  - The present study was undertaken to determine the toxicity of scorpion (Buthus
      tamulus) venom in young and adult rats, as well as in different species of adult
      animals (rats, mice and guinea-pigs). The median lethal dose (LD50; mg/kg s.c.)
      of scorpion venom in young and adult rats was 2.2 +/- 0.21 and 1.3 +/- 0.14,
      respectively. The LD50 value for mice (7.2 +/- 1.35) was significantly greater
      than adult rats or guinea-pigs (1.14 +/- 0.08). The LD50 dose for i.v. route in
      anaesthetized adult rats was 95 +/- 13.2 micrograms/kg weight, which is 13 times
      less than that required for s.c. route. The results show that the lethality of
      scorpion venom in mammals differs with the age and species of the animals.

PMID- 8146876
TI  - Myocarditis following envenoming with Vipera palaestinae in two horses.
AB  - Cardiac disease developed several days to weeks after resolution of local
      inflammation caused by envenoming by Vipera palaestinae in two horses. In one
      horse (case A), referred to the hospital for recurrent abdominal pain 8 days
      after envenoming, a tachyarrhythmia was detected; ventricular premature
      depolarizations were diagnosed by ECG. A second horse (case B) was found dead
      without premonitory signs 60 days after envenoming. In both horses, there was
      extensive necrosis of cardiac ventricular tissues.

PMID- 8146877
TI  - Bibliography of toxinology.

PMID- 8146878
TI  - Signals for protein targeting into and across membranes.

PMID- 8146879
TI  - Compartments of the early secretory pathway.

PMID- 8146880
TI  - Assembly of mitochondrial membranes.

PMID- 8146881
TI  - The assembly of chloroplast membranes.
AB  - During the last five or six years there has been a shift in focus in the field of
      chloroplast protein transport, with greater emphasis being placed on
      understanding the sorting of proteins to the thylakoids and the envelope
      membranes. As a result, we have a much-improved understanding of the variety of
      important pathways that function during chloroplast biogenesis. It is now clear
      that a considerable number of distinct intraorganellar sorting mechanisms operate
      to direct imported proteins to their correct destinations. Some of the underlying
      mechanisms are also beginning to emerge, although it is accurate to say that we
      are still a long way from understanding in genuine detail how proteins are
      translocated across chloroplast membranes. However, the availability of such a
      range of efficient in vitro import assays should ensure that rapid progress is
      made in coming years. The major gaps in this field now concern the identities and
      roles of the elements of the important apparatus: Although at least two distinct
      translocation systems operate during chloroplast biogenesis, none of these
      components has been identified, purified, or cloned. This is primarily because
      these proteins are often difficult to assay individually, and they are usually of
      very low abundance. Nevertheless, it is essential that progress is made in this
      area soon in order to maintain the present momentum.

PMID- 8146882
TI  - Biogenesis of the lysosomal membrane.

PMID- 8146883
TI  - Insertion of proteins into membranes. A survey.

PMID- 8146884
TI  - Assembly of the peroxisomal membrane.

PMID- 8146885
TI  - Nuclear envelope assembly and disassembly.

PMID- 8146886
TI  - Membrane assembly in bacteria.

PMID- 8146887
TI  - Ischemic effects on the structure and function of the plasma membrane.

PMID- 8146888
TI  - The major glycosylation pathways of mammalian membranes. A summary.

PMID- 8146889
TI  - Designer red cells.

PMID- 8146890
TI  - Epidemiologic comparison of human T-lymphotropic virus type I-infected blood
      donors from endemic and nonendemic regions over a 3-year period.
AB  - BACKGROUND: Screening for human T-lymphotropic virus type I (HTLV-I) infection
      became systematic in 1989 in the French West Indies for blood from all donors and
      in France for blood from natives of endemic areas; in 1990, it was extended to
      blood from donors with at-risk sex partners and in July 1991 to blood from all
      donors. STUDY DESIGN AND METHODS: The epidemiologic characteristics of
      individuals found through the screening of donated blood to be HTLV-I infected
      were compared for an endemic region (Guadeloupe, French West Indies) and a
      nonendemic region (Paris area) over a 3-year period (1989 through 1991). RESULTS:
      In Guadeloupe, 131 HTLV-I-infected individuals were detected in the screening of
      28,801 units; in the Paris area, 38 HTLV-I-infected donors were detected in the
      screening of 109,824 units. All Guadeloupean HTLV-I-infected donors were natives
      of endemic areas. Among the 38 Parisian HTLV-I-infected donors, 21 were natives
      of endemic areas, 10 were natives of endemic areas and had received transfusions,
      2 were whites who had received transfusions, and 5 were whites who had had
      heterosexual contact with natives of endemic areas. The percentage of HTLV-I
      infected individuals whose blood would have been excluded because of positivity
      for one or more markers for other viruses did not significantly change over the
      study period and did not significantly differ between regions (41%). Among the
      eight Parisian HTLV-I-infected blood donors detected after July 1991, six would
      not have been detected without the biologic screening. CONCLUSION: The
      generalization of biologic screening of HTLV-I-infected donated blood in France
      was useful for the prevention of HTLV-I and HTLV type II infections through
      transfusion.

PMID- 8146891
TI  - Evaluation of clinical and laboratory aspects of antibody tests for detection of
      hepatitis C virus infection in blood donors and recipients from a low-risk
      population.
AB  - BACKGROUND: When the first-generation enzyme immunoassay (EIA) for detection of
      antibody to hepatitis C virus (anti-HCV) was approved in May 1990, blood banking
      agencies recommended testing of all components in inventory. In many cases, one
      or more components from these units had already been transfused. STUDY DESIGN AND
      METHODS: Donors that reacted in first-generation EIAs and recipients of their
      components were identified, and anti-HCV test methods (including first-generation
      EIA, second-generation EIA, and recombinant immunoblot assay [RIBA]) were
      evaluated. RESULTS: Of 66 donors identified as anti-HCV-positive by first
      generation EIA, 17 were positive in second-generation EIA. Of these 17, 9 reacted
      in RIBA; 6 of these showed evidence of HCV infection in polymerase chain reaction
      (4) and/or probable transmission of HCV to a transfusion recipient (3). Of the 48
      specimens that were positive in first-generation EIA and negative in second
      generation EIA, only 1 was positive in RIBA; serum was not available for
      polymerase chain reaction testing, and there were no living transfusion
      recipients in whom to assess evidence of transmission of HCV. CONCLUSION: This
      study documents the low predictive value of EIAs for anti-HCV in a low-prevalence
      blood donor population and emphasizes the need for additional testing to confirm
      the specificity of samples that react in the screening tests.

PMID- 8146892
TI  - Transfusions to group O subjects of 2 units of red cells enzymatically converted
      from group B to group O.
AB  - BACKGROUND: It has previously been shown that full-unit (200 mL) transfusions of
      red cells (RBCs) enzymatically converted from group B to group O by treatment
      with alpha-galactosidase (ECO RBCs) are both safe and efficacious for normal
      group O or A subjects. STUDY DESIGN AND METHODS: The present study describes the
      results of a comprehensive clinical and serologic assessment of 2-unit (400 mL)
      ECO RBC transfusions to each of four normal group O subjects (after each had
      donated 1 unit of whole blood). RESULTS: Clinical (hematologic tests, chemistry
      analysis, urinalysis) and serologic analyses revealed no evidence of immediate or
      delayed transfusion reaction, despite a threefold to fivefold elevation in pre
      existing anti-B antiglobulin titer. 51Cr-labeled ECO RBCs were administered to
      one of the four subjects to allow direct measurement of ECO RBC survival in the
      circulation, which indicated that it was normal (24-hour survival, 95%; t1/2,
      29.5 days). The observed increases in hemoglobin (by 1.3 +/- 0.4 g/dL [13 +/- 4
      g/L]) and hematocrit (by 3.2 +/- 0.8% [0.032 +/- 0.008]) in transfused subjects
      provide further evidence of the efficacy of these cells in vivo. CONCLUSION:
      These results extend those observed in our earlier 1-unit transfusion studies and
      suggest that ECO RBCs pose little risk and will be useful in transfusion
      medicine.

PMID- 8146893
TI  - Independent roles for platelet crossmatching and HLA in the selection of
      platelets for alloimmunized patients.
AB  - BACKGROUND: Although HLA-matched platelets are frequently requested for
      alloimmunized patients, recent evidence has indicated that 1-hour posttransfusion
      platelet increments in these patients are specifically sensitive to crossmatch
      compatibility. STUDY DESIGN AND METHODS: To determine the extent of advantage
      gained by use of single-donor apheresis (SD) platelets selected on the basis of
      HLA match when crossmatch-compatible SD platelets were available, a total of 220
      platelet transfusions given in the absence of individually determined significant
      nonimmune factors were analyzed in a well-characterized cohort of platelet
      refractory patients. Platelets were selected by solid-phase crossmatch from a
      small donor pool of relatively poor HLA matches or, upon request, ordered as HLA
      matched and later crossmatched. RESULTS: Alloimmunized patients responded better
      to SD platelets selected on the basis of HLA than to pooled platelet concentrates
      or SD platelets selected at random, although most of the benefit was limited to
      the 57-percent subset of good HLA matches. Crossmatch-compatible SD platelets
      provided similar posttransfusion platelet increments independent of the HLA
      match. None of 31 crossmatch-incompatible SD platelets transfused provided an
      adequate increment, including 13 that were ordered as HLA-matched platelets.
      CONCLUSION: No benefit could be demonstrated from requesting that SD platelets be
      HLA-matched when crossmatch-compatible SD platelets were available.

PMID- 8146894
TI  - Lack of effect on platelet increments of granulocyte-macrophage-colony
      stimulating factor following autologous bone marrow transplantation for malignant
      lymphoma.
AB  - BACKGROUND: Recombinant growth factors are used increasingly often to stimulate
      bone marrow recovery after intensive chemotherapy and bone marrow
      transplantation. Their effects on the requirements for and responsiveness to
      coincident therapies, including transfusion, should be defined. STUDY DESIGN AND
      METHODS: To determine whether treatment with recombinant granulocyte-macrophage
      colony-stimulating factor (GM-CSF) affects platelet transfusion responsiveness,
      the clinical and blood bank records were examined for 16 adult patients (8
      controls, 8 receiving GM-CSF) participating in a double-blind study of GM-CSF
      administration (250 micrograms/m2 x 21 days) following autologous bone marrow
      transplantation for lymphoma. For each platelet transfusion, a corrected count
      increment was calculated, and note was made of the presence or absence of
      selected additional factors thought to decrease platelet responsiveness: fever,
      amphotericin treatment, HLA antibodies, platelet ABO incompatibility, and febrile
      transfusion reactions. RESULTS: The total number of platelet transfusions (GM-CSF
      patients, 145; controls, 145) and the mean number of transfusions per patient (GM
      CSF, 18.3; controls, 18.0) were comparable in the two groups. GM-CSF patients
      received significantly more platelets that were ABO incompatible, that were given
      during a febrile period, or that were given while the patient was on
      amphotericin. Nevertheless, the corrected count increments in patients who
      received GM-CSF were at least as good as those in controls: for GM-CSF patients:
      mean was 8,574 +/- 5,868, median was 7,818, 49 percent were < 7,500 and 66
      percent were < 10,000; for controls; mean was 7,618 +/- 7,536, median was 6,100,
      59 percent were < 7,500, and 73 percent were < 10,000. CONCLUSION: In this group
      of patients, GM-CSF did not adversely affect the required number of, increments
      to, or incidence of refractoriness to platelet transfusions.

PMID- 8146895
TI  - Granulocyte transfusions: efficacy in treating fungal infections in neutropenic
      patients following bone marrow transplantation.
AB  - BACKGROUND: A retrospective study was conducted to evaluate the efficacy of
      granulocyte transfusions in neutropenic patients with fungal infections following
      bone marrow transplantation. STUDY DESIGN AND METHODS: Systemic fungal infection
      was detected in 87 patients during the first 100 days following bone marrow
      transplantation; 50 received granulocytes in addition to appropriate antifungal
      agents. The median age was 17 years in the transfused patients (range, 1.5-57)
      and 35 years in the nontransfused patients (range, 0.8-50). Granulocyte
      transfusions were given on a daily to twice-daily basis. To evaluate their
      responses, patients were categorized by infection type (candidal [n = 38] vs.
      noncandidal [n = 49]) and site (fungemia alone [n = 30] vs. invasive infection [n
      = 57]). Resolution of infection was defined as the resolution of signs and
      symptoms and negative cultures and/or histopathology. RESULTS: No benefit of
      granulocyte transfusions could be shown in the resolution of infection in
      patients with either invasive noncandidal infection (29% in the transfused
      patients vs. 23% in the nontransfused patients, p > 0.1) or candidal sepsis (56%
      vs. 50%, p > 0.1). Among patients with delayed marrow recovery, no difference was
      seen in the resolution of infection in the transfused (25.9%) and nontransfused
      (50%) patients (p > 0.1); nor was any difference between the transfused and
      nontransfused patients evident in the duration of febrile episode associated with
      the fungal infection. Granulocyte transfusions were well tolerated, with the only
      complications being fever in 12 patients (24%), chills in 10 (20%), and
      respiratory distress in 2 (4%). Despite attempts to stratify by infection type,
      invasiveness, and marrow recovery, it was not possible to show any benefit of
      granulocyte transfusions in this group. CONCLUSIONS: It is likely that only
      through a prospective randomized trial can the question of the efficacy of
      granulocyte transfusions in treating fungal infections be conclusively answered.

PMID- 8146896
TI  - A flow cytometric method for phenotyping recipient red cells following
      transfusion.
AB  - BACKGROUND: Reticulocyte phenotyping is used for transfused patients, who have
      red cell antibodies, to match blood for subsequent transfusion. Current methods
      are labor-intensive and require a significant amount of sample. STUDY DESIGN AND
      METHODS: A simple dual-color flow cytometry method developed for antigen typing
      of reticulocytes in mixed red cell populations is reported. Antigens were labeled
      by an indirect immunofluorescence technique using undiluted reagent sera as the
      primary label, biotinylated goat anti-human IgG as the secondary label, and
      avidin-phycoerythrin as the fluorescent stain. Reticulocytes were labeled with a
      thiazole orange fluorescent stain. Reticulocyte identification and antigen typing
      were performed on 319 samples to establish the validity of the procedure. Mixed
      red cells were prepared in all possible c antigen combinations to simulate
      transfusion concentrations of 25, 50, and 75 percent. RESULTS: The anti-c flow
      cytometry profiles readily distinguished between antigen-positive and antigen
      negative populations and allowed the detection of reticulocytes at all simulated
      transfusion concentrations. Similar results were obtained in experiments using C,
      K, s, Fya, Fyb, Jka, or Jkb sera against equal volumes of antigen-positive and 
      negative cells. Anti-S gave inconsistent results. The in vitro results were
      confirmed in 19 transfused patients who had received red cells antigenically
      different from their own as well as cells from 1 chimera blood donor. CONCLUSION:
      This method provides a simpler, safer, less labor-intensive, and less subjective
      technique requiring far less sample volume than current methods for antigen
      typing of reticulocytes in mixed red cell samples from recently transfused
      patients.

PMID- 8146897
TI  - A survey of the incidence of Miltenberger antibodies among Hong Kong Chinese
      blood donors.
AB  - BACKGROUND: The ready availability of red cells of the Miltenberger (Mi) class
      III phenotype (6.28%) prompted the study of Mi antibodies among Chinese blood
      donors in Hong Kong, 98 percent of whom are descended from inhabitants of
      Guangdong Province in southern China. STUDY DESIGN AND METHODS: Red cells of the
      Mi class III phenotype were used to conduct a survey of the frequency of
      Miltenberger antibodies in 56,161 random Chinese blood donors, over a period of
      12 months, using a microplate technique. RESULTS: Sera from 32 donors (0.057%)
      were found to contain Mi antibodies: sera from 22 contained anti-Mur + Hut; sera
      from 4 contained anti-Vw + Mur + Hut; sera from 4 had monospecific anti-Mur; and
      sera from 2 had monospecific anti-Hil. The immunoglobulin isotypes of 24 sera
      were mixtures of IgM and IgG, 4 were pure IgM, and 4 were pure IgG. CONCLUSION:
      The majority of Mi antibodies detected were naturally occurring. This survey
      proved useful for mass screening of random donors for the procurement of valuable
      Mi antisera.

PMID- 8146898
TI  - Protective effect of blood transfusions on postoperative recurrence of Crohn's
      disease in parous women.
AB  - BACKGROUND: Perioperative blood transfusion (BT) appeared to have adverse effects
      on survival after surgery for malignant tumors while pretransplantation BT
      suppressed allograft rejection. Interest grew in the effect of BT on
      postoperative recurrence of Crohn's disease. STUDY DESIGN AND METHODS: To
      determine the effect of perioperative BT on the recurrence of Crohn's disease
      after primary surgery, the medical histories of 148 patients with Crohn's
      disease, 62 males and 86 females (49 nonparous and 37 parous), were reviewed.
      Eighty-seven patients received perioperative BT. RESULTS: Overall, perioperative
      BT showed no effect on recurrence. Patients with Crohn's disease limited to the
      ileum had a better prognosis with regard to recurrence than did patients with
      Crohn's disease located in the colon or located in both ileum and colon, but the
      difference was not significant. Perioperative transfusion seemed to protect
      against recurrent disease after colon resection, which might be explained by the
      fact that colon resections, which often necessitate perioperative BT, generally
      result in a shorter bowel segment at risk for recurrent disease. Overall, parous
      women showed a worse prognosis than nonparous females and men (p = 0.022).
      Transfusions had a beneficial effect in parous women (p = 0.068) and, after
      correction for type of operation, this beneficial effect was significant (p =
      0.026). After perioperative BT, parous women had a similar prognosis with respect
      to recurrent Crohn's disease as nonparous females and men. CONCLUSION:
      Perioperative BT has a beneficial effect on the postoperative recurrence of
      Crohn's disease in parous women.

PMID- 8146899
TI  - Fatal disseminated intravascular coagulation and pulmonary thrombosis following
      blood transfusion in a patient with severe autoimmune hemolytic anemia and human
      immunodeficiency virus infection.
AB  - BACKGROUND: Autoimmune hemolytic anemia (AIHA) has rarely been reported in
      association with human immunodeficiency (HIV) infection and never as a presenting
      manifestation. Similarly, disseminated intravascular coagulation (DIC) is a very
      infrequent complication of HIV infection. CASE REPORT: An unusual patient is
      described who at the time of presentation with severe AIHA was found to be HIV
      positive. Shortly thereafter, he developed DIC, pulmonary thrombi, and right
      heart failure that proved fatal, in spite of intensive supportive measures.
      CONCLUSION: Although the etiology of the DIC and pulmonary thrombi could not be
      established, they are most likely related to aggressive transfusion therapy, with
      associated intravascular hemolysis.

PMID- 8146900
TI  - Pseudoaneurysm of the brachial artery: a rare complication of blood donation.
AB  - BACKGROUND: Serious complications of blood donation are rare. Reported here is a
      significant vascular event that resulted from whole-blood phlebotomy and required
      surgical repair. CASE REPORT: A 49-year-old woman donated whole blood without
      incident in November 1992, but reported ecchymosis and tenderness in the
      antecubital area of the right arm immediately following the procedure (her
      medical history was unremarkable). Over the next several days, the ecchymosis
      extended to the axilla and she complained of numbness in all her fingers,
      particularly the thumb and adjacent two fingers of the involved side. Coincident
      to these findings, an egg-sized lump developed under the skin at the phlebotomy
      site. Her symptoms and the mass persisted for several weeks. Examination and
      ultrasound performed in January 1993 demonstrated a pulsatile mass over the
      brachial artery. The donor underwent an exploratory surgical procedure that
      revealed a 3.3 x 2.5 x 2.0-cm pseudoaneurysm of the brachial artery. Unlike a
      true aneurysm, this lesion was composed only of a blood clot that was compressing
      the outer wall of the artery. A pinpoint-sized hole was seen in the artery when
      the lesion was excised. The phlebotomy is believed to have caused blood to leak
      out of the artery, creating the lesion and exerting pressure on the median nerve.
      CONCLUSION: Pseudoaneurysm of the femoral artery is a well-documented
      complication of cardiac catheterization and other invasive arterial procedures,
      but this is the first known reported case following blood donation. Blood
      collectors should be made aware of this potentially serious complication of blood
      donation.

PMID- 8146901
TI  - Sulindac-induced immune hemolytic anemia.
AB  - BACKGROUND: Sulindac, a nonsteroidal, anti-inflammatory, indene-derived drug,
      caused life-threatening immune hemolytic anemia in an individual with back pain.
      CASE REPORT: A patient was admitted to the hospital with immune hemolytic anemia
      and kidney and liver failure after several days ingestion of sulindac. The direct
      antiglobulin test was positive with polyspecific and monospecific anti-IgG but
      not with anti-C3. The eluate did not react in routine tests but reacted strongly
      after the addition of sulindac. The serum contained a sulindac-dependent antibody
      reacting to a titer of 32. The sulindac-dependent antibody was of both IgG and
      IgM classes and had no apparent blood group specificity. The antibody
      agglutinated red cells from humans and chimpanzees but not from chickens,
      rabbits, or sheep, which implied that a specific component on human and
      chimpanzee red cells was needed for reactivity. The antibody reacted with red
      cells treated with trypsin, papain, pronase, dithiothreitol, and sialidase. With
      aggressive medical care, the patient's condition improved. CONCLUSION: These
      findings appear compatible with the so-called immune complex mechanism for drug
      induced immune hemolytic anemia. Physicians are alerted to the severe nature of
      this syndrome.

PMID- 8146902
TI  - On improving the cost-effectiveness of autologous blood transfusion practices.

PMID- 8146903
TI  - Controversies in transfusion medicine. Perioperative hemodilution: pro.
AB  - Hemodilution can obviate the need for allogeneic transfusion in some patients.
      However, it is only one component of a comprehensive blood conservation program
      and should be combined with other techniques whenever possible. While most often
      employed in teenagers and healthy young adults, ANH has been used in small
      children, the elderly, and patients of all ages who are undergoing cardiac
      surgery. Extreme caution should be exercised if ANH is used in patients with
      coronary artery disease or aortic stenosis who are undergoing noncardiac surgery,
      because their normal compensatory mechanisms are impaired. What usually is a safe
      and relatively simple procedure can become a disaster if employed in
      inappropriately selected patients. Careful hemodynamic monitoring and maintenance
      of normovolemia are critical.

PMID- 8146904
TI  - Controversies in transfusion medicine. Acute normovolemic hemodilution in
      elective major surgery: con.

PMID- 8146905
TI  - The evolution of the current blood banking regulatory climate.

PMID- 8146906
TI  - Reinstatement of donors who test false-positive in second-generation hepatitis C
      virus enzyme immunoassay should await availability of licensed third-generation
      tests.

PMID- 8146907
TI  - Red cell viability with infusion systems.

PMID- 8146908
TI  - Filamentous fungi: old mutants and new discoveries.

PMID- 8146909
TI  - Genetic patterns of plant host-parasite interactions.
AB  - A parasite's ability to infect and a host's ability to resist infection can be
      heritable traits. Patterns of inheritance suggest how host genes interact with
      parasite genes to determine whether or not infection occurs. Recent progress in
      the isolation and characterization of these genes in plants sheds new light on
      parasitism.

PMID- 8146910
TI  - What do BMPs do in mammals? Clues from the mouse short-ear mutation.
AB  - Bone morphogenetic proteins (BMPs) are a family of secreted signaling molecules
      that were originally isolated on the basis of their remarkable ability to induce
      the formation of ectopic bones when implanted into adult animals. The first
      mutations identified in a mammalian BMP gene suggest that members of this family
      induce the formation, patterning and repair of particular morphological features
      in higher animals.

PMID- 8146911
TI  - The 530 loop of 16S rRNA: a signal to EF-Tu?
AB  - The molecular mechanism of tRNA selection has remained elusive. Recent evidence,
      both biochemical and genetic, suggests the involvement of 'smart' ribosomes, that
      can signal the elongation factor Tu by way of conformational changes in ribosomal
      RNA.

PMID- 8146912
TI  - Long-term cryoconservation of the halotolerant alga Dunaliella.

PMID- 8146913
TI  - Glucanex: a cost-effective yeast lytic enzyme.

PMID- 8146914
TI  - Electroporation of cosmid DNA into bacterial cells.

PMID- 8146915
TI  - The strange phylogenies of transposable elements: are horizontal transfers the
      only explantation?
AB  - Analyses of the evolution of transposable elements reveal some inconsistencies
      when the phylogenies of such elements are compared to conventional phylogenies of
      the host species. Such discrepancies are generally interpreted as resulting from
      occasional horizontal transfers of transposable elements across species
      boundaries. This phenomenon has been clearly demonstrated for only a few elements
      and both its frequency and the mechanism by which it occurs remain unknown.
      Moreover, in many cases, the hypothesis of horizontal transfer must be compared
      with alternative evolutionary scenarios.

PMID- 8146916
TI  - [Effect of continuous change in axial position in treatment of post-traumatic
      lung failure (ARDS). A clinical study].
AB  - In the treatment of posttraumatic adult respiratory distress syndrome (ARDS) so
      far no breakthrough has been achieved. In several cases of severe ARDS we have
      seen improvements of lung function by means of continuous body positioning. We
      therefore compared the effect of kinetic positioning (KIN) on lung function and
      hemodynamics in ARDS patients to conventional (KON) supine positioning. 22 ARDS
      patients with multiple trauma treated by supportive continuous body positioning
      (KIN) (KCI-Mediscus) and without continuous positioning (KON) were investigated
      daily. Pulmonary and systemic hemodynamics were determined on the basis of
      pulmonary artery catheter measurements. Oxygenation ratio (PaO2/FiO2) and
      pulmonary shunt (Qs/Qt,%) were calculated. Extravascular lung water (EVLW, ml/kg
      body weight) was determined by double indicator thermodilution technique. Total
      injury severity by injury severity score (ISS) was 29.6 +/- 6 points (KIN) and
      31.6 +/- 5 points (KON). The oxygenation ratio (PaO2/FiO2) increased
      significantly from 140 +/- 45 (day 0) to 237 +/- 40 (p < 0.05) [day 5] (KIN), in
      KON patients no improvement (143 +/- 48 [day 0], 133 +/- 44 [ay 5]) was seen (p <
      0.05 between groups). There were no significant changes of systemic hemodynamics
      between the groups or compared to day 0. Pulmonary shunt decreased significantly
      from 26.6 +/- 4% (day 0) to 12.5 +/- 2% (day 5) (p < 0.05) in KIN patients and
      was 36.6 +/- 6% at day 0 and 31.4 +/- 2% at day 5 in KON patients (p < 0.05
      between groups). EVLW was 11.1 +/- 2 ml/kg body weight at day 0 and 9.4 +/- 1
      ml/kg body weight at day 5 (KIN)-EVLW was 12.9 +/- 2 ml/kg body weight at day 0
      and 17.4 +/- 3 ml/kg body weight at day 5 (KON) (not significant). We found no
      hemodynamic side effects from continuous body positioning. In ARDS-patients
      submitted to body positioning oxygenation and pulmonary shunt improved
      significantly and were significantly better compared to those with conventional
      supine positioning. Continuous body positioning appears to represent a promising
      supportive treatment regimen in posttraumatic ARDS.

PMID- 8146917
TI  - [Pelvic fractures in the Kiel trauma surgery clinic. A one-year evaluation].
AB  - 48 injuries to the pelvis were treated from January 1991 through December 1991.
      We found 45 fractures of the pelvic ring with associated acetabular fractures in
      15 cases and three isolated acetabular lesions. 19 injuries were caused by car
      accidents, 18 fractures resulted from a fall, especially in older patients.
      Isolated fractures of the pelvis occurred in 18 cases. The average total severity
      of the injuries was 19.7 points according to the Hannover Polytrauma Score (PTS).
      Every fracture was classified using the Tile-classification. There were 15 (33%)
      Tile A lesions, 18 (40%) Tile B fractures and twelve (27%) type C pelvic ring
      injuries. In 18 cases surgery was the method of treatment. Seven out of 18
      injuries to the acetabulum were treated with open reduction and internal
      fixation. In ten patients the unstable pelvic ring was fixed by means of an
      external fixator. To do so, a pair of 6 mm diameter pins were placed on both
      sides in the supraacetabular region of the iliac bone directed towards the
      sacroiliac joints. We used a triangular form of external fixation. An open
      reduction and internal fixation (ORIF) was necessary in five cases, one injury
      required a combination of external and internal procedures. There were 14 cases
      in which we found sacral fractures as an additional dorsal lesion. Nine of 14
      sacral fractures were recognized only by CT examination. In eleven cases the
      conventional radiographs showed simple anterior pelvic ring fractures while the
      CT examination revealed an additional lesion of the sacroiliac joint in nine of
      these cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146918
TI  - [Joint bridging external fixation of fractures of the distal lower leg with
      severe skin damage].
AB  - During the 36 months from April 1989 until April 1992, 34 fractures of the lower
      end of the leg were treated by joint bridging application of external fixation
      using the so-called ".. Kugelspannfixateur UNIFIX". They were: 24 intraarticular
      compression fractures, seven bimalleolar dislocation fractures, two shot
      fractures and one postoperative empyema. All demanded treatment urgently. Because
      of severe skin lesions or because of medical reasons, neither osteosynthesis nur
      conventional conservative methods could be used. With the aid of UNIFIX, good
      alignment was achieved in all cases and practically always maintained as long as
      necessary. Reduction of joint-bearing fragments was equally good as with
      ligamentotaxis. All skin lesions healed during the time of fixation. Only two
      infections of screw tracks were observed. Additional operations like primary
      minimal osteosynthesis or later reconstructive surgery could be carried out with
      the fixateur in place. They have improved the results. No severe damage to the
      subtalar joint was observed. Therefore this principle of treatment can be
      recommended providing right indication.

PMID- 8146919
TI  - [Indications for vein interposition in microsurgical reconstruction of complex
      defects of the lower extremity after tumor and trauma].
AB  - Reconstructive microsurgery has become a routine procedure in plastic surgery.
      Success rates in major centers range between 95 and 98%. In selected "high risk"
      cases, vein grafts are required to facilitate microsurgical anastomoses, as in
      complex defects of the lower leg, post ischemic syndrome (PIS) or following major
      tumor resections. The indications and results of vein grafts or A-V loops are
      demonstrated in these three groups. 25 patients with defects of the lower leg
      were operated using vein interposition grafts. Ten A-V loops were created prior
      to flap transfer. Three flaps had to be revised, only one flap was lost due to
      recurrent arterial thromboembolism from an injured proximal segment. Data show
      that vein grafts are clinically reliable and may be used without hesitation in
      appropriate clinical situations.

PMID- 8146920
TI  - [Indications, technique and results of treatment of fractures of the base of the
      first metacarpal bone with movement stable osteosynthesis].
AB  - We report about the indication, technique and results of 27 fractures of the base
      of the metacarpus I. All those fractures were treated by open reduction and screw
      /plate osteosynthesis according to the AOSIF-technique. Using these implants and
      the technique of open reduction with an additional autologous bone graft it
      offers the possibility to start active motion therapy immediately after
      operation. Perioperative complications can be bypassed with the use of external
      mini-fixateur as well as in those cases of open fractures with various types of
      damage patterns. Total active mobility (TAM) of the thumb joints showed in our
      series of 27 treated fractures an active total mobility of 80% or more in 25
      patients. There where three patients with wound healing disturbances. No fracture
      healed delayed or resulted in non union, no patient showed signs of reflex
      dystrophy, yet in two cases insufficient joint reconstruction had to be noted.
      Neither our own short followed-up results or those few cases published so far
      allow us a final critical judgement of the best technique in treating the
      fractures of the base of metacarpus I.

PMID- 8146921
TI  - [Dislocation of the knee joint with lesion of the popliteal artery. A case
      report].
AB  - Complete dislocation of the knee is rare but frequently associated with popliteal
      artery disruption. Prompt recognition and early revascularisation are paramount
      for a successful and functional result. We report on a case of anterior
      dislocation of the knee complicated by concomitant popliteal artery injury. The
      value of pre-operative diagnostic methods including pre-operative arteriography
      and Doppler-sonography is discussed. Review of literature is presented.

PMID- 8146922
TI  - [The physician continuing education regulation as a means for quality assurance].

PMID- 8146923
TI  - [Urology in the woman. Part 1: Conservative and interventional therapy].

PMID- 8146924
TI  - [New developments in surgical technique].

PMID- 8146925
TI  - [Reconstruction of the lower urinary tract after cystectomy. Experiences and
      results in 126 patients with the Kock ileum reservoir in conjunction with
      bilateral ureteroileourethrostomy].
AB  - Between May 1986 and February 1990, 126 consecutive men underwent lower urinary
      tract reconstruction by means of bilateral ureteroileal urethrostomy using a Kock
      ileal reservoir. The early complication rate was 11.1%. Late complications
      requiring rehospitalization or reoperation have been surprisingly few: 1 for
      prolapse of the afferent antirefluxing nipple valve, 1 for calculi and 4 for
      artificial urinary sphincter placement due to unsatisfactory continence. Good
      continence has been achieved in 94% of the patients during the day and in 84% at
      night. Tumor recurred in the pelvis in 5 patients, with 4 requiring cutaneous
      urinary diversion. All patients had progression or died of metastatic disease.
      Our experience has yielded extraordinary results in terms of patients acceptance
      with few late complications or need for reoperation.

PMID- 8146926
TI  - [Reconstruction of the bladder neck after radical retropubic prostatectomy using
      a tubular bladder flap].
AB  - To improve urinary continence after retropubic prostatectomy, especially in the
      early postoperative phase, we used a 1.5 cm tubularized anterior bladder flap for
      bladder neck reconstruction in 30 patients. We compared the continence rates of
      these patients with 30 patients with standard bladder neck closure operated on in
      the same period of time. Continence rates were assessed by a personal interview 1
      day after catheter removal (postoperative day 22) and 3 months postoperatively by
      a questionnaire. While only 2/30 (6.6%) of the patients with standard bladder
      neck closure were completely continent 1 day after catheter removal, 9/30 (30%)
      of the patients with the tubularized neourethra were completely dry. After 3
      months the standard procedure led to a 58% rate of complete continence. This was
      achieved in 75% of patients with the tubularized flap. Ten percent of the
      patients with conventional operations developed a bladder neck contracture. This
      complication occurred in 20% of the patients with the new method. Analyzing
      subgroups, we found that patients with a tubularized neourethra who received
      adjuvant irradiation of the prostatic bed because of positive surgical margins
      developed a bladder neck stenosis in 40% of the cases due to shrinking of the
      flap.

PMID- 8146927
TI  - [Laparoscopic retroperitoneal lymph node excision in clinical stage I non
      seminomatous testicular cancer].
AB  - Modified retroperitoneal lymph node dissection for stage I testicular tumors has
      been described by Weissbach. For performing laparoscopic retroperitoneal
      lymphadenectomy within these boundaries, we have developed a two-step procedure.
      In the first step, a ventral approach is used. The colon is dissected free, then
      the spermatic vein is excised, and the borders of dissection are defined. Removal
      of retroaortic and retrocaval nodal tissue is technically not feasible from the
      ventral approach. Therefore, in the second step, a lateral approach is employed,
      which is the key to success since it allows for easy transection of the lumbar
      vessels. Thus complete lymph node dissection can be realized. Between August 1992
      and June 1993 this procedure was performed in 11 patients. In 7 patients, the
      tumor was on the right side and in 4 on the left. Conversion to open surgery was
      necessary in two patients because of uncontrollable bleeding and a large
      metastasis, respectively. Microscopic metastases were detected in two other
      patients. No major complications occurred; no blood transfusions were required.
      So far, the results have been encouraging.

PMID- 8146928
TI  - [Value of the neurovascular guide plate for pelvic surgery].
AB  - In the past few years great effort has been made to reduce the morbidity after
      oncologic operations in the small pelvis of the male. In this respect it is
      essential for urologic surgeons to orient themselves with the anatomic structures
      that mark the course of the important vessels and nerves. For this reason an
      anatomic study of the connective tissue in the male pelvis was performed in which
      dissections and serial sections were analyzed. The results show that the
      connective tissue in the male pelvis does not represent a monomorphic block but
      consists of several portions of varying density. The looser portions are also
      known as the "connective tissue spaces" of the pelvis. The comparatively dense
      portions--the so-called "vessel-nerve guiding plate" and its three "connective
      tissue pillars"--envelop the vessels and nerves supplying the corresponding
      pelvic organs. Therefore, they provide ideal landmarks for urologic surgery.

PMID- 8146929
TI  - [Nerve preserving retroperitoneal lymph node excision in non-seminomatous
      testicular cancer].
AB  - Thirty-nine patients with a non-seminomatous testicular tumor underwent
      retroperitoneal lymphadenectomy (RPLND) between 12/90 and 7/93. Twenty-four
      patients with stage I disease were operated on with a modified nerve-sparing
      RPLND, while 7 patients with stage IIA and 8 patients with stage IIB had
      bilateral RPLND. Twelve of fifteen patients with stage IIA and IIB had
      preservation of their sympathetic postsynaptic fibers. Intraoperative electric
      stimulation of the fibers resulted in ejaculation in 25/26 patients. Semen
      analysis revealed 21 patients with necrospermia and maturation arrest, while 3
      had aspermia. Antegrade ejaculation was restored after 1.1 months following nerve
      sparing RPLND and 7 months following radical RPLND. Ejaculation did not return in
      one patient. No patient showed relapse. Our results show that the sympathetic
      postsynaptic fibers can be preserved during RPLND. Nerve-sparing RPLND is
      superior to radical and modified RPLND with regard to preservation of ejaculation
      without compromising the radicalness of the tumor surgery.

PMID- 8146930
TI  - [Microsurgical techniques in urology].
AB  - Microsurgery is an established operative technique for refertilization by
      vasovasostomy, tubulovasostomy and microsurgical epididymal sperm aspiration.
      Other andrological indications for the use of a microscope are penile
      revascularization, resection of varicocele and surgical treatment of Peyronie's
      disease. Autotransplantation of intra-abdominal testicles and hypospadia
      correction are indications for microsurgical techniques in pediatric urological
      surgery. Renal transplant, sex-change surgery and replants of penis and scrotum
      are further indications for use of microsurgery. Microsurgery will move into new
      fields of urological surgery, especially neurourology.

PMID- 8146931
TI  - [Microsurgical therapy of occlusive azoospermia].
AB  - From 5/88 to 8/93 148 patients were operated on for obstructive azoospermia using
      a microsurgical technique. In 68 patients we performed a vasectomy reversal by
      vasovasostomy (VT), 42 patients underwent a tubulovasostomy (TT), and 8 patients
      had a VT with contralateral TT. Two patients had implantation of an alloplastic
      spermatocele, 9 patients had microsurgical epididymal sperm aspiration (MESA),
      and 19 patients microsurgical exploration. Patency was achieved in 89% of
      patients after VT and in 32% after TT. A pregnancy occurred in 34% after VT and
      in 13% after TT. No pregnancy was achieved after MESA or alloplastic
      spermatocele. A microsurgical procedure is necessary for the treatment of
      congenital or acquired obstructive azoospermia.

PMID- 8146932
TI  - [Functional results and complications of the ileal neobladder in over 200
      patients].
AB  - Between April 1986 and October 1992, a total of 229 patients with invasive
      bladder cancer underwent radical cystectomy and lower urinary tract
      reconstruction by means of the ileal neobladder. The perioperative mortality was
      2.4%. Subsequently 10.5% of the patients suffered from early complications that
      led to relaparotomy and 3.8% of the patients had bowel occlusion. Significant
      late complications were urethro-ileal strictures (6.7%) and stenosis of the
      ureteral anastomosis (3.3%). Despite a very strict definition of continence, only
      2 patients with a follow up of more than 2 years had an incontinence grade 3.
      Most (77%) of the patients in this collective were perfectly continent day and
      night, while 11.5% had only occasional spotting and wore pads to be on the safe
      side. In conclusion, the medium-term results are now available (average follow up
      41 months) and show that the ileal neobladder is the treatment of choice for male
      patients after radical cystectomy for the treatment of invasive bladder cancer.

PMID- 8146933
TI  - [Laparoscopic ligation of spermatic vessels in varicocele].
AB  - Open surgical procedures and percutaneous transvenous radiological techniques are
      available for the treatment of varicoceles. With the advent of laparoscopic
      surgery another minimally invasive procedure has become available. In 39 patients
      with left unilateral and 1 with bilateral, clinically evident, varicocele
      laparoscopic ligation of the spermatic vessels was performed. In 17 cases both
      the spermatic veins and the artery were cut, whereas in 24 cases it was possible
      to spare the spermatic artery. In more than 90% of these cases the artery could
      be identified as a pulsatile vessel. No serious complications were encountered.
      All patients were discharged from the hospital on postoperative day 1 or 2. Out
      of 26 patients who could be followed clinically and by colour coded Duplex
      sonography, 1 showed signs of persistent and 1 of recurrent varicocele. The quick
      convalescence of the mostly young patients, the excellent identification of the
      anatomic structures, and the minimal surgical trauma are advantages of
      laparoscopic varicocelectomy.

PMID- 8146934
TI  - [Radiotelemetric manometry of the urinary bladder].
AB  - The standard procedure for manometric investigation of bladder function involves
      the use of a urethral catheter. The presence of this foreign body causes
      irritations, however, with a resultant increase in urethral resistance. This
      perturbs the micturition process, but it can be avoided by a new telemetric
      method of intravesical pressure measurements. A very small pressure gauge and
      radio emitter are introduced into the bladder, and the values measured are
      transmitted to an external receiver. Thus, for the first time, is possible to
      perform physiological studies of bladder function that do not require
      catheterization or special positioning of the patient and are well tolerated.
      Some examples are described, which show that this method allows repeated catheter
      free investigations over longer periods of time and accurate evaluation of the
      effects of pharmacological products on bladder function.

PMID- 8146935
TI  - [Incidence and differential diagnosis of hyperechoic kidney tumors].
AB  - The frequency of kidney tumours was determined in a prospective study of 11,076
      consecutive patients investigated sonographically in a department of internal
      medicine. A further objective of the study was to establish whether the echo
      characteristics of the renal tumours alone allow sonographic categorization into
      benign and malignant tumours, how often it is possible to diagnose
      angiomyolipomas of the kidneys on the basis of sonography alone, and how
      frequently further imaging techniques and/or invasive methods are necessary. In
      this patient series, 68 solid renal lesions were detected (0.6%): 15 of the
      lesions were hypernephroid carcinomas (0.13%) and 28 angiomyolipomas (0.25%). All
      angiomyolipomas were hyperechoic. In contrast, only 3 of the hyperechoic tumours
      were hypernephroid carcinomas. Owing to the unequivocal sonographic appearance,
      16 out of 28 angiomyolipomas could be diagnosed on the basis of sonography alone.
      Additional diagnostic measures were necessary for only 12 of these tumours (CT,
      angiography, intravenous pyelogram, and an operation in 1 patient, who had an
      angiomyolipoma infiltrating into the vena cava). In contrast to this, computer
      tomography was necessary in addition for the diagnosis of all malignant tumours,
      and angiography in 4 cases.

PMID- 8146936
TI  - [Erectile dysfunction and hypogonadism. Is routine endocrine screening
      necessary?].
AB  - Erectile dysfunction is rarely caused by hypogonadism. We distinguish between
      primary and secondary hypogonadism. Among 70 consecutive men treated for
      impotence within 1 year in the authors' clinic, the rate of endocrinopathy was
      4.3%. The exact role of testosterone in male sexual function is unclear.
      Testosterone replacement may be helpful only in patients with low serum
      testosterone and decreased libido. Endocrine screening is necessary in impotent
      patients with clinical signs of hypogonadism. Patients with decreased libido and
      no signs of hypogonadism should also be undergo endocrine evaluation. Routine
      endocrine testing for all patients with erectile dysfunction is expensive and not
      productive.

PMID- 8146937
TI  - [Kidney cancer and angiomyolipoma in lymphangiomyomatosis].
AB  - Lymphangiomyomatosis is an extremely rare benign disease characterized by
      extensive proliferation of smooth muscle cells within lymphatic vessels and lymph
      nodes. While 10-15% of all patients show concomitant renal angiomyolipomas, no
      association so far has been reported with renal cell carcinoma. We present a case
      with coincident lymphangiomyomatosis, renal cell carcinoma and renal
      angiomyolipoma. The possible underlying pathogenesis is discussed. Classifying
      lymphangiomyomatosis as a "forme fruste" of tuberous sclerosis allows postulation
      of a common pathogenesis for all three entities.

PMID- 8146938
TI  - [Bilateral ureteral obstruction by granuloma formation in chronic
      granulomatosis].
AB  - A 24-year-old patient with chronic granulomatous disease had bilateral
      hydronephrosis resulting from ureteral granuloma formation. He was treated with
      high-dose steroids, antibiotics and percutaneous nephrostomy. The etiology,
      incidence, clinical findings and treatment of chronic granulomatous disease are
      discussed.

PMID- 8146939
TI  - [Bilateral ureteroiliac fistula coincident with radiotherapy and ureteral
      splint].
AB  - Fistulas between the iliac artery and the ureter are uncommon. Overall, fewer
      than 20 cases have been described in the literature. We report the first
      bilateral case, in which there was an association with indwelling bilateral
      ureteral stents and a history of radiation therapy following hysterectomy
      performed because of malignancy. The patient presented with massive gross
      haematuria.

PMID- 8146940
TI  - [Report of experience in reconstruction of the lower urinary tract in the man and
      woman].
AB  - For some decades uretero(ileo) cutaneostomy and ureterosigmoidostomy were the
      methods of choice for urinary diversion in cystectomized patients. In recent
      years, lower urinary tract reconstruction with an anastomosis from an intestinal
      urinary reservoir to the urethra has established itself as an alternative for
      male patients undergoing cystectomy. We present the results obtained in 35
      patients (32 men, 3 women) who chose to have a ureteroileal urethrostomy to the
      residual urethra after radical cystectomy for bladder cancer. These patients were
      followed up by clinical, serologic, radiographic, and urodynamic evaluation
      conducted at short intervals according to a strict protocol. There was no
      perioperative mortality, and the early postoperative complication rate was 17%
      (6/35 patients). For all patients, including those followed only for 3 months so
      far, the diurnal continence rate was 87% and the nocturnal continence rate was
      78%. In every patient, male and female, the maximum urethral pressure (average
      value in the urethra pressure profile 50.8 cm H2O) was higher than the average
      resting intraluminal pressure in the pouch (average 12 cm H2O) with physiologic
      capacity (250-550 ml) of the urinary bladder. Patient acceptance, measured on a
      numerical self-rating scale, was high (average value 8.75 out of 10).

PMID- 8146941
TI  - [Cooperative responsibility of insured clients in case of occupational
      disability].

PMID- 8146942
TI  - [Sequelae of cannabis use--results of a survey of experts on traffic accidents
      and "echopsychoses" (flash-back)].
AB  - There is a lack of knowledge in the judgement of the effects and the
      dangerousness of cannabis. Specially in the judgement of the delinquency of
      traffic the effects must be clarified. Cannabis plays often a fundamental role in
      road accidents. Obviously flash-backs of consumers of cannabis are observed more
      often than documented in the literature hitherto. The existing but not published
      experiences of experts have to be considered extensively to get an idea more
      complete of the diverse effects of cannabis in traffic offences.

PMID- 8146943
TI  - [The biological marker CDT--its possible importance for insurance medicine].
AB  - Current biochemical markers of heavy alcohol intake are of limited diagnostic
      utility for detecting alcohol abuse in an early stage. A new indicator, the
      Carbohydrate-deficient Transferrin (CDT), was recently introduced for clinical
      use. Its characteristics and possible use for insurance medicine are presented.

PMID- 8146944
TI  - [Sudden cardiac death and occupational activity].
AB  - 4578 persons who died suddenly from natural reason were dissected in the Center
      of Legal Medicine of the University of Frankfurt am Main between 1979 and 1988.
      Among those were 2542 with sudden cardiac death. In 776 cases a relation between
      the occupation and the danger of dying of a sudden cardiac death could be proved.
      All the others had to be eliminated of the statistics, either because they were
      already retired when they died or because the occupation couldn't be found out.
      Altogether 142 different occupations were registered. A great percentage of the
      dissected people were construction workers, members of the safety duty and the
      transportation business and managers. Also butchers, bakers and cooks appeared
      quite often in the exploration, but never a shoemaker or a theologist.

PMID- 8146945
TI  - [Mortality in relation to type of insurance--an empirical study with
      representative German data 1974 to 1990].
AB  - In Germany different forms of insurance funds (private funds, social security for
      blue collar or for white collar workers, firm-specific funds) secure against
      sickness risks. Actual governmental policy is to increase the competition between
      funds by introducing the possibility to switch from one to the other. In order to
      compensate for the differences in risk of health status between individual
      members a compensation payment planned according to age and sex of the members.
      In 1974 a representative sample of the adult West German population has been
      asked about its sickness fund membership (among other questions). A new
      epidemiological concept, the demographic variant of the relative survival method,
      is used here to determine whether mortality in the 16 years after 1974 differed
      between the sickness fund members. Even after exact demographic control members
      of private sickness funds survived considerably better than members of other
      insurance funds. The highest mortality was found for members of the social
      security of blue collar workers (AOK). These results show that apart from the
      pure demographic factors other important health related differences exist between
      members of different sickness funds.

PMID- 8146946
TI  - [Insurance medicine in routine forensic medicine].
AB  - When the forensic doctor is confronted with a query coming from the insurance
      medicine, he will perhaps realize, that he has suddenly reached the boundaries of
      his knowledge. Statutory regulations are partly not yet available and partly
      contested. This accounts for the fact, that sometimes ten or more expert opinions
      are formulated for one and the same litigation. In the present paper some themes
      are randomly selected and reviewed in accordance with scientific findings.
      Investigated with references pertaining to current points at issues, are the
      following controversial subjects: a) Victim compensation law b) Nursing insurance
      law c) Transplantation law d) Acceleration trauma e) Lightning casualties f)
      Heroin (drug criminality) g) Age determination h) Insurance fraud The practice
      shows, that the physician's need to search for causality is restricted by
      juridical thought, be it by legal enactments or by the superior courts' guiding
      principles.

PMID- 8146947
TI  - [Diagnosis--versus pseudo-syndrome related medicine].
AB  - One essential prerequisite for the high therapeutic effectiveness of scientific
      based medicine is to find out the most exact diagnosis as possible. This
      principle is disregarded from the pseudo-syndrome related medicine. This wide
      spread medical practise leads to unclear diagnostic entities. For this reason,
      grave shortcomings e. g. for therapy emerge.

PMID- 8146948
TI  - [Fee for physician services in completing a life insurance examination].
AB  - The question if reports and examinations by medical doctors in the completion of
      a life insurance policy must be charged according to the official German schedule
      of fees for medical doctors (GOA) is answered differently in the literature. As
      the GOA has legal force, an account according to the GOA is prescribed if there
      is no other conclusion between insurance company and medical doctor. Indisputably
      an account according to the GOA must be made for additional medical achievements
      such as laboratory examinations, electrocardiography and x-ray examinations.
      Insurance companies that offer for the medical report or the examination a fee
      within the regular limits of the GOA-numbers cannot be blamed to offer an
      inadequate fee.

PMID- 8146949
TI  - [Epidemiology of suicide].
AB  - 1. Nationwide surveys in single countries concerning epidemiology of suicide are
      in fact valuable despite serious doubts often mentioned against them. 2. From the
      beginning of this century until the 1980's there has been an almost continuous
      increase in the number of suicides in males. Since the end of the 1950's the
      figure of female suicide has risen in various countries as well, although the
      situation is not the same everywhere. 3. Denmark proved to be the country with
      the highest suicide rate within the European Community, whereas it is Hungary in
      Eastern Europe. The former GDR had rates above the average in 1988-90.
      Extraordinarily low rates were seen in Greece, Spain, Ireland and Italy. 4. The
      elderly tended to have increasing rates in most countries--with the exception of
      regional varieties in connection with drug abuse and alcoholism as well as
      unemployment. 5. Suicides in psychiatric clinics demonstrated a rise worldwide-
      studies carried out in the Federal Republic of Germany reported of such suicides
      having doubled since the beginning of the 1970's. 6. Vast regional differences in
      major cities of the FRG had been described in the 60's and 70's. In the former
      GDR there were strong discrepancies between various regions in 1988-90. Those
      data are not explainable yet.

PMID- 8146950
TI  - Enhancement of the increase in intracellular calcium concentration in stimulated
      neutrophils by Mycoplasma hyopneumoniae.
AB  - Neutrophils isolated from the peripheral blood of pigs free of infection with
      Mycoplasma hyopneumoniae were loaded with a fluorescent indicator (Fura-2) for
      detection of cytosolic free calcium concentration. The kinetics of the
      intracellular calcium flux were examined after incubation with or without a
      pathogenic or a non-pathogenic strain of M. hyopneumoniae. The basal
      intracellular calcium concentration was not altered by incubation with M.
      hyopneumoniae. However, the relative increase in cytoplasmic calcium
      concentration caused by the addition of opsonized zymosan was significantly (p <
      0.05) higher in neutrophils incubated with M. hyopneumoniae as compared to
      neutrophils not incubated with M. hyopneumoniae. Additionally, after zymosan
      stimulation, the intracellular calcium concentration was greater in neutrophils
      incubated with a pathogenic strain of M. hyopneumoniae than in those incubated
      with a non-pathogenic strain. This suggests that M. hyopneumoniae alters the
      signal transduction mechanisms in neutrophils and that this alteration may be
      related to virulence.

PMID- 8146951
TI  - Canine C-reactive protein (CRP) does not share common antigenicity with human
      CRP.
AB  - Differences in antigenicity between human and canine C-reactive proteins were
      investigated by Western blotting analysis. It was confirmed that several
      commercial anti-human CRP sera reacted with canine CRP. However, 34 anti-canine
      CRP sera prepared by immunization of rabbits and goats with canine CRP all
      reacted with canine CRP but not with human CRP in either immunoelectrophoresis or
      Western blotting. Immunization with human CRP produced a cross-reacting antibody
      that reacted with canine CRP. Conversely, immunization with canine CRP did not
      produce a cross-reacting antibody that reacted with human CRP. These findings may
      be interpreted as showing that, while canine and human CRPs do not share common
      antigenicity, they do contain structurally similar antigenic determinants.

PMID- 8146953
TI  - Identification of a nasal nematode (Eucoleus boehmi) in greyhounds.
AB  - Eggs of Eucoleus boehmi were recovered from the faeces of greyhounds from three
      breeding farms and four racetrack kennels and from those of four greyhounds
      submitted for necropsy. Diagnosis was dependent on differentiation of the eggs of
      E. boehmi, E. aerophilus and Trichuris vulpis. Quantitative fecal examinations
      conducted weekly for 24 weeks in one greyhound suggested that the egg shedding
      pattern of E. boehmi is cyclical. Nasal swabs failed to reveal eggs of E. boehmi,
      but nasal washings gave positive results. Because of its small size (15-40 mm)
      its location within the epithelial lining of the nasal mucosa, turbinates, and
      sinuses, and difficulty in differentiating the bipolar plugged eggs, E. boehmi
      probably occurs more often than is currently diagnosed.

PMID- 8146952
TI  - Crossed immunoelectrophoresis of fungal antigens in tissues as a means of
      diagnosing systemic aspergillosis and zygomycosis in cattle.
AB  - A novel method for diagnosing bovine aspergillosis and zygomycosis is described.
      Rabbit hyperimmune antisera raised against somatic antigens of Aspergillus
      fumigatus and Absidia corymbifera were used in crossed immunoelectrophoresis with
      supernatants from disintegrated tissues from acute necrohaemorrhagic mycotic
      lesions from cattle. The method specifically identified 4 of 5 lesions with
      aspergillosis and 2 of 5 lesions with zygomycosis. One lesion dually infected
      with aspergillosis and zygomycosis was negative. The method worked with
      unabsorbed sera, was specific, and required only standard electrophoretic
      equipment. It can therefore supplement chemical detection of fungi in tissues in
      the diagnosis of bovine aspergillosis and zygomycosis.

PMID- 8146954
TI  - The effects of naturally deoxynivalenol-contaminated oats on the clinical
      condition, blood parameters, performance and carcass composition of growing pigs.
AB  - A feeding trial with naturally deoxynivalenol (DON)-contaminated oats included in
      feed mixtures at graded levels was conducted in growing pigs. The DON
      concentrations were 0, 0.7, 1.7, and 3.5 mg/kg of complete feed mixture given ad
      libitum to different groups. The data recorded were feed consumption, body weight
      gain, slaughter weight, biochemical and haematological data including serum
      immunoglobulin A, clinical condition and post-mortem pathology including
      histopathology. Significantly decreasing body weight gain throughout the
      experimental period, decreased slaughter weight and reduced feed utilization
      efficiency were observed for the group fed a diet containing 3.5 mg/kg of DON. At
      the same DON concentration, there were increased liver weights and decreased
      concentrations of serum protein and albumin, and a temporary fall in packed blood
      cell volume, serum calcium and serum phosphorus. For the groups fed diets
      containing 1.7 and 3.5 mg/kg of DON, a statistically significant, dose-related
      decrease in daily feed consumption was observed. No other effects on
      haematological, biochemical or immunological parameters were recorded. The
      carcass quality was not affected in any group. It was concluded that significant
      effects in growing pigs may be observed at a dietary DON concentration of 1.7
      mg/kg, originating from naturally contaminated oats included in a diet that was
      otherwise adequate and contained only minor traces of other mycotoxins.

PMID- 8146955
TI  - The pharmacokinetics of thiamphenicol in lactating cows.
AB  - The pharmacokinetics of thiamphenicol were studied after intravenous and
      intramuscular administration of 25 mg/kg body weight in lactating cows.
      Distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives of 6.10 +/- 1.39
      min and 1.60 +/- 0.30 h, respectively, were obtained after intravenous
      administration. The body clearance was 3.9 +/- 0.077 ml/kg per min and the
      apparent volume of distribution was 1220.79 +/- 256.67 ml/kg. The rate at which
      thiamphenicol appeared in the milk, as indicated by the penetration half-life
      (t1/2P) (serum to quarters), was found to be 36.89 +/- 11.14 min. The equivalent
      elimination half-life (t1/2E) (quarters to serum) from the milk was 3.62 +/- 1.06
      h and the peak thiamphenicol concentration in the milk was 23.09 +/- 3.42
      micrograms/ml at 2.5 +/- 0.32 h. After intramuscular injection, the elimination
      half-life was 2.2 +/- 0.40 h, the absorption half-life was 4.02 +/- 1.72 min and
      the peak concentration in the serum was 30.90 +/- 5.24 micrograms/ml at 23 +/-
      8.4 min. The bioavailability after intramuscular administration approached 100%.
      The penetration half-life was 50.59 +/- 6.87 min, the elimination half-life was
      5.91 +/- 4.97 h and the mean peak concentration in the milk was 17.37 +/- 2.20
      micrograms/ml at 3.4 +/- 0.22 h.

PMID- 8146956
TI  - Pharmacokinetics of benzydamine in dairy cows following intravenous or
      intramuscular administration.
AB  - Five lactating cows were given benzydamine hydrochloride by rapid intravenous
      (0.45 mg/kg) and by intramuscular (0.45 and 1.2 mg/kg) injection in a crossover
      design. The bioavailability, pharmacokinetic parameters and excretion in milk of
      benzydamine were evaluated. After intravenous administration, the disposition
      kinetics of benzydamine was best described using a two-compartment open model.
      Drug disposition and elimination were fast (t1/2 alpha: 11.13 +/- 3.76 min; t1/2
      beta: 71.98 +/- 24.75 min; MRT 70.69 +/- 11.97 min). Benzydamine was widely
      distributed in the body fluids and tissues (Vd(area): 3.549 +/- 1.301 L/kg) and
      characterized by a high value for body clearance (33.00 +/- 5.54 ml/kg per min).
      After intramuscular administration the serum concentration-time curves fitted a
      one-compartment open model. Following a dose of 0.45 mg/kg, the Cmax value was
      38.13 +/- 4.2 ng/ml at a tmax of 67.13 +/- 4.00 min; MAT and MRT were 207.33 +/-
      22.64 min and 278.01 +/- 12.22 min, respectively. Benzydamine bioavailability was
      very high (92.07% +/- 7.08%). An increased intramuscular dose (1.2 mg/kg)
      resulted in longer serum persistence (MRT 420.34 +/- 86.39 min) of the drug,
      which was also detectable in milk samples collected from both the first and
      second milking after treatment.

PMID- 8146957
TI  - The uptake of fenbendazole by cattle and buffalo following long-term low-level
      administration in urea-molasses blocks: further studies on block formulations.
AB  - Fenbendazole (Hoechst India Ltd.) was incorporated at 0.5 g/kg into urea molasses
      blocks made by two different processes. The proportion of the drug remaining in
      the blocks and the plasma concentrations of the parent compound and its
      metabolites were measured. Recovery of the drug in blocks made by the cold and
      the modified hot processes was 90% and 96%, respectively. The plasma metabolite
      profile revealed a plateau between days 4 and 6 of feeding in cattle and buffalo.
      However, the plasma concentrations of fenbendazole and its metabolites were low
      in buffalo compared to cattle.

PMID- 8146958
TI  - [Teaching in initial military medical training in medical schools].

PMID- 8146959
TI  - [The work organization of an office of ultrasonic studies in a polyclinic].
AB  - In the process of work of ultrasound room the optimal correlation between various
      ultrasound examinations was found out: hepato-pancreatico-biliary system-40%,
      urogenital system-30%, thyroid-15%, uterus and its appendages-5%, lactiferous
      glands-5%, other examinations-5%. Special coupons were issued for passing
      ultrasound examination: it gives the possibility to plan the maximal working
      loads at matutinal hours, keeping the end of the working day for strictly
      specialized ultrasound examinations.

PMID- 8146960
TI  - [Current problems in the intensive therapy of patients with acute pneumonia].

PMID- 8146961
TI  - [Trophological insufficiency and the criteria for its diagnosis].
AB  - The health of a man considerably depends on his nutritional status. The present
      day defects in dietary are frequently acting as the main "killers" and
      "pathogens" in the modern human society. The poor dietary could considerably
      change the protective status of a human organism and influence upon the course of
      diseases. The article makes a definition of the "trophological status" and
      describes various methods of its estimation which could be successfully applied
      for an early diagnosis of trophological insufficiency in servicemen.

PMID- 8146962
TI  - [Multiple organ failure in peritonitis].

PMID- 8146963
TI  - [The relationship of diseases to different blood groups].

PMID- 8146964
TI  - [Sudden hearing loss in inner ear trauma].
AB  - Quite often a sudden surdity can appear after baro or mechanical traumas, it
      happens because of rupture of the round window membrane which leads to the
      formation of the perilymphatic fistula. The article deals with the syndrome of
      the round window membrane rupture. The authors describe two successful cases of
      treatment of patients with vestibular disorders caused by posttraumatic
      perilymphatic fistula. Practical recommendations are given for providing a
      tertiary medical care in emergency situations.

PMID- 8146965
TI  - [A congenital anomaly of the crystalline lens erroneously related to radiation
      exposure].

PMID- 8146966
TI  - [The organization of dispensary observation for persons with a history of
      infectious diseases in Afghanistan].
AB  - Outpatient control over the patients who went through infectious diseases in
      Afghanistan is determined by a structure of the dominant nosological forms of
      infectious diseases: typhoid, paratyphoid, intestinal amebiasis and other acute
      intestinal infections, viral hepatitis, malaria. A considerable number of
      servicemen who went through infectious diseases had led to a re-enforcement of
      "infections service" inside the organic structure of the 40th Army, as well as to
      elaboration of a rational system of outpatient control, including regular medical
      examinations by organic physicians, and infectionists, laboratory, functional and
      instrumental methods of examination by organic medical units and specialized
      health care establishments and sanitary-epidemiological units.

PMID- 8146967
TI  - [The prospects for using permethrin for individual protection against blood
      sucking arthropods].

PMID- 8146968
TI  - [Diagnosis and prognosis in determining the priority of care for the victims in
      mass casualties].

PMID- 8146969
TI  - [The participation of the epidemiological health institutions of the Ministry of
      Defense of the Russian Federation in the dynamic health observation of
      servicemen].
AB  - Actually clinical physicians use the method of "cabinet" questionnaire to
      disclose the risk factors, including harmful professional conditions, which can
      worsen the health status of servicemen. These data obtained during check-up is
      not completely summarized or used to study the influence of the environment upon
      the health of military community. The authors proposal is to coordinate the
      system of sanitary and hygienic support with the system of medical examination
      during the whole period of dynamic observation. For example, at the stage of
      profound medical observation it is possible to resort to consultation of
      hygienist in order to make a precise primary diagnosis and divide examinees into
      two groups: the former composed of healthy servicemen, and the latter of patients
      with doubtful health status.

PMID- 8146970
TI  - [Pharmacological agents for the correction of the processes of work capacity
      rehabilitation in flight personnel].
AB  - Pharmacological correction of performance capability of rehabilitation processes
      in flight crews depends on the character and intensity of sustained loads under
      the influence of flight and corresponding changes of energoplastical synthesis in
      human organism. The authors make a proposal to influence upon the processes of
      energoproducts not only after the work (postlabour rehabilitation), and
      immediately in the process of work (current rehabilitation), but also before the
      flight activities (preventive rehabilitation). The article contains the results
      of administration of bemitil, panangin, asaparal, acephen, fenibut, natrium
      oxibutirate and ascorbic acid. There are recommendations for aviation physicians
      concerning the usage of these medications for performance capability correction
      of the flight crews.

PMID- 8146971
TI  - [The 125th anniversary of the Saint Petersburg Declaration on the Prohibition of
      the Use of Dumdum Bullets].

PMID- 8146972
TI  - [The holder of regimental command decorations (on the 90th anniversary of the
      birth of N. P. Ustinov)].

PMID- 8146973
TI  - [The 60th anniversary of the creation of the Research Institute of Microbiology
      of the Ministry of Defense of the Russian Federation].

PMID- 8146974
TI  - [The development of methods and agents for the prevention of combat mental trauma
      in the U.S. Army].

PMID- 8146975
TI  - [The use of an automated teaching system in a therapy department].
AB  - At the division of general therapy N 1 of the Kirov Military Medical Academy a
      version of automated training system was elaborated for the IBM AT/386 users of
      MS DOS operational system. The knowledge text control was carried out during the
      lessons at the display classroom equipped with Wyse-85 terminals ("Wyse
      Technology Company"), DEC VT 220 regimen, and connected up to PC IBM AT/386 which
      works in multiterminal function. Application of text control has shown that the
      volume of knowledge had increased up to 82-90%, but it was right only for the
      groups where the methodics of classes with application of the results of text
      controls was strictly adhered. The progress in other groups was less than 68%.

PMID- 8146976
TI  - Sensitivity of the fibrinogen clotting time: an in vitro test of potential
      thrombogenicity.
AB  - The fibrinogen clotting time (FCT) is a measure of thrombin activity, and is used
      to evaluate the potential thrombogenicity of prothrombin complex concentrates
      (PCC). We have defined end points for clot formation in this test which allow the
      measurement in PCC of thrombin concentrations as low as 0.001 IU/ml. The FCT of
      thrombin and PCC samples which did not contain antithrombin III (ATIII) were the
      same when measured at 20 degrees C or 37 degrees C. In the presence of ATIII
      (0.05 or 0.25 IU/ml), samples of PCC which were known to contain thrombin showed
      shorter FCT at 20 degrees C than at 37 degrees C. Inclusion of both ATIII (0.25
      IU/ml) and heparin (4 IU/ml) in PCC ensured the complete inactivation of
      endogenous thrombin.

PMID- 8146977
TI  - Effect of prestorage leukocyte removal on the cytokine levels in stored platelet
      concentrates.
AB  - The effect of the prestorage removal of leukocytes from platelet concentrates
      (PC) on the cytokine levels during its storage was studied. Two methods for
      leukocyte removal were examined: filtration and preparation of the PC by the
      buffy coat method. Cytokine levels were measured at various storage times. Highly
      increased levels of tumor necrosis factor-alpha (TNF-alpha; 120 +/- 131 ng/l) and
      interleukin 6 (IL-6; 988 +/- 494 ng/l) were found after a 5-day storage in the
      control group, whereas no increased levels were found in filtered PC (TNF-alpha
      14 +/- 4 ng/l, IL-6 < 4 ng/l) or in buffy coat PC (TNF-alpha 8 +/- 2 ng/l, IL-6 <
      4 ng/l). Furthermore an effect of the pooling of buffy coats or PC on the
      cytokine levels was not found. Transfusion of PC containing high levels of IL-6
      and TNF-alpha has been associated with febrile transfusion reactions in the
      recipient and therefore the prestorage leukocyte removal might prevent these
      febrile transfusion reactions. The preparation of buffy coat PC, through its
      simplicity, seems to be the method of choice.

PMID- 8146979
TI  - Multicenter evaluation of methods for counting residual white cells in leukocyte
      depleted red blood cells. The Biomedical Excellence for Safer Transfusion (BEST)
      Working Party of the International Society of Blood Transfusion.
AB  - Two wet workshops were conducted involving 20 laboratories to determine optimum
      methods for counting residual white blood cells (WBC) in leukocyte-depleted red
      blood cells (RBC). In both studies, calibration samples containing known
      concentrations of WBC were prepared by diluting 1-day-old EDTA blood in RBC
      virtually free of WBC. Study No. 1 was aimed at determining the lower limit of
      detection and at examining advantages and disadvantages of two methods based on
      flow cytometry (FC) and on the Nageotte chamber (NC), respectively. This study
      showed that the lower detection limits for FC and NC were 0.1 and 1
      WBC/microliters, respectively. Methods based on FC showed less variability at 0.1
      1 WBC/microliters but were equal in performance to counting procedures based on
      the NC above 1 WBC/microliters. We then designed study No. 2 to evaluate three
      different protocols using the NC. In protocol 1, samples were diluted 1:10 with
      Plaxan and with Turk's solution; in protocol 2 a mixture of Turk's solution and
      Zap-oglobin, a reagent used in manual hemoglobin determinations, was used to
      dilute the samples 1:5; and protocol 3 involved initial 1:10 dilution of a 1-ml
      sample with Plaxan followed by WBC concentration into the original 1-ml volume by
      centrifugation. In each participating laboratory, two technologists independently
      processed the samples and read the results with an NC. Plaxan and Turk's solution
      gave comparable results. Interobserver variability was not critical to the
      results. All three NC methods were valid for counting at concentrations of > or =
      1 WBC/microliters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146978
TI  - Platelets stored for 6 days in a polyolefin container in a synthetic medium with
      minimal plasma carry-over.
AB  - Platelet concentrates (PC) were stored for 6 days in either polyolefin (PO) or
      polyvinylchloride/di-(2-ethylhexyl)phtalate (PVC/DEHP) bags in 100% plasma or in
      a synthetic medium with 35 or 10% plasma. For all conditions studied the usual in
      vitro parameters were well maintained, with a pH above 6.8. In both bag types
      platelets can be satisfactorily stored for 6 days in a synthetic medium with
      minimal amounts of residual plasma. For this medium, the PO bag offers a slight
      advantage with respect to the preservation of platelet ATP content (> 80 versus >
      70% in the PVC bags) and aggregation and adhesion capacity. The adhesion capacity
      increased in the PO bags, while it decreased in the PVC bags.

PMID- 8146980
TI  - Second-generation anti-HCV screening in a Saudi Arabian donor population.
AB  - The 2nd-generation anti-HCV test system was applied to a Saudi Arabian multi
      ethnic donor population. When donors were stratified according to first-time
      donations versus repeat donations, the latter having been screened previously by
      a 1st-generation set of tests, it was found that in Saudi Arabian and Middle East
      nationals, the 2nd-generation tests (EIA and RIBA), identified close to double
      the number of anti-HCV-positive donors, compared to an earlier study using the
      1st-generation tests. Part of this finding was due to a 38% higher rate of RIBA
      confirmable repeat-positive EIA results. In groups of donors, previously screened
      by the 1st-generation system, some additional cases of anti-HCV reactivity were
      identified, most prominently in Middle East nationals. It is assumed that some of
      these represented recent seroconversions, while others were cases of serologic
      subtypes of HCV, not reacting in the 1st-generation tests. The current test
      system identifies 0.66% of Saudi-Arabian, and 2.87% of other Middle East donors
      as putative carriers of hepatitis C virus. The study lends support to the opinion
      that donors who return regularly over the years have a lower prevalence of
      disease markers, thereby being a safer source of blood than first-time donors.

PMID- 8146981
TI  - Alloimmunisation via previous transfusion places female Kpb-negative recipients
      at risk for having children with clinically significant hemolytic disease of the
      newborn.
AB  - We report a case of clinically significant hemolytic disease of the newborn due
      to Kpb alloimmunisation requiring obstetric intervention. This case and a review
      of the literature are in contrast to reviews of hemolytic disease of the newborn
      that either ascribe no significance to the Kpb antigen or suggest that it causes
      only rare or mild disease. Analysis of our Kpb-negative donor pool suggests that
      prior transfusion greatly increases the chance of alloimmunisation. The role of
      frozen rare donor registry cells as a public resource is emphasised.

PMID- 8146982
TI  - Pure anti-Doa stimulated by pregnancy.
AB  - Pure anti-Doa stimulated by pregnancy was detected in 2 non-transfused females
      during routine antenatal screening. Anti-Doa occurs rarely and has generally been
      reported in combination with other antibodies. The first, and only report to
      date, of pure anti-Doa was also stimulated by pregnancy. We believe these
      instances to be only the second and third reported cases of pure anti-Doa.

PMID- 8146983
TI  - A human monoclonal antibody to high-frequency red cell antigen Jra.
AB  - A human-mouse heterohybridoma (HMR0921) secreting human monoclonal IgG3, lambda
      antibody was produced from peripheral blood lymphocytes of a healthy blood donor
      with serum antibody to Jra, by EBV transformation and hybridization with mouse
      myeloma cell line P3X63Ag8.653. The reactivity of HMR0921 antibody was assessed
      by antiglobulin test with a panel of red cells including 14 different rare blood
      types. Only Jr(a-) red cells were negative. The strict specificity of this
      antibody to Jra antigen was further confirmed by absorption test with
      fluorescence flow cytometry. On screening of 28,744 blood donor samples by
      HMR0921 antibody, we detected 19 agglutination-negative samples, which were
      confirmed as Jr(a-) by conventional anti-Jra antisera. Therefore, our HMR0921
      antibody is extremely useful for detecting rare Jr(a-) blood.

PMID- 8146984
TI  - Human monoclonal antibodies against the rhesus D antigen from women with severe
      Rh immunization submitted to high-dose intravenous immunoglobulin treatment.
AB  - The pre- and postpartum maternal serum anti-D concentrations of 28 women with
      severe Rh(D) immunization who received high-dose intravenous immunoglobulin
      treatment has been determined. In all cases, including 1 in which the newborn was
      D negative, a sharp increment in the anti-D titer was observed after delivery.
      The specific immunoglobulin concentration rose to levels ranging from 4.7 to
      204.0 micrograms/ml and, in 20% of the patients, increments of fifty times or
      greater were observed. Human monoclonal antibodies (hmAb) have been produced from
      Epstein-Barr virus-transformed lymphoblastoid B cell lines derived from 1 of
      these naturally hyperimmunized patients whose serum contained an anti-D-category
      DVI antibody. Four anti-D-secreting cell lines (97.E3.39.214, 44.E4.R1.257,
      E7.R1.126.83.115 and E11V.117.63; hereafter referred to as 214, 257, 115 and 63)
      have been established and maintained in continuous culture for periods ranging
      from several months to 3 years, without loss of antibody production capacity.
      Antibodies 115 and 214 recognize all Du samples tested at the same level as the
      polyclonal positive control. Antibodies 63 and 257 show a significantly lower
      reaction strength with some of the Du samples. Studies with D category cells
      showed that the DVI category was recognized only by hmAb 214. The reactivity
      pattern of this antibody is that of an anti-epD4, although the reaction strength
      varied greatly with different DIVa cell samples. Results obtained with hmAb 257
      and 115 using papain-treated D category cells suggest that booth react as anti
      epD6/7.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8146985
TI  - Production of a new murine monoclonal antibody with Fy6 specificity and
      characterization of the immunopurified N-glycosylated Duffy-active molecule.
AB  - A murine monoclonal antibody (mAb i3A; IgG1, kappa light chain) was obtained
      using human red blood cells as immunogen. The antibody showed Fy6 specificity
      since it agglutinated all but Fy(a-b-)-untreated red cells and failed to
      agglutinate chymotrypsin-treated cells. An erythrocyte membrane protein of 42-46
      kD was revealed as the major component recognized by the antibody on immunoblots.
      The antibody also bound to 92- to 95- and 200-kD proteins, tentatively identified
      as oligomers of the 42- to 46-kD monomeric form. The affinity-purified Fy6-active
      protein was converted to a sharp band of 35 kD after N-glycanase treatment. The
      molecule appeared as a slightly broadly band after neuraminidase treatment but
      was not further altered by O-glycanase. The i3A mAb bound to 6,000 +/- 1,000
      receptor sites on either Fy(a-b+), Fy (a+b+) and Fy(a+b-) red cells with an
      affinity constant in the range of 3-6 x 10(8) M-1. No binding was observed to
      other blood cells nor to several cells (B, T, myelomonocytic and erythro-leukemia
      cell lines). Also, the bulk of i3A-Fy6 immune complexes could be dissociated from
      the red cell membrane with as low as 0.2% Triton X-100, showing that the Fy6
      active glycoprotein is not tightly associated with the membrane skeleton. Our
      data obtained with a new monoclonal antibody directed to the Fy6 antigen
      demonstrate that the blood group Duffy-active component is a red cell-specific
      glycoprotein carrying one or more N-linked oligosaccharides.

PMID- 8146986
TI  - A novel variant of the human blood group K1 antigen.
AB  - A discrepancy in duplicate anti-K1 typing in a parentage case led to the
      discovery of an unusual K1 blood group antigen. Red blood cells from the
      propositus (JC) express a rare variant of the K1 antigen that is detectable by
      only 8 of 72 sera containing anti-K1. Absorption and elution studies using
      reactive anti-K1 confirmed the presence of a K1 antigen. Nonreactive anti-K1 was
      not absorbed by or eluted from JC's red blood cells. Red cells from 3 of the
      propositus's siblings also had the variant K1 antigen. The variant antigen
      exhibited qualitative as well as quantitative differences as compared to normal
      K1, and we have named it K1var.

PMID- 8146987
TI  - Evidence for expression of the Joa blood group antigen on the Gya/Hy-active
      glycoprotein.
AB  - The phenotypic association between the non-assigned high-incidence antigen Joa
      and the Gya collection antigens Gya and Hy was investigated by haemagglutination
      studies, flow cytometric analysis, immune precipitation and immunoblotting
      experiments. In haemagglutination tests anti-Joa gave the same pattern of
      reactivity with erythrocytes pre-treated with pronase, trypsin, alpha
      chymotrypsin and thiol reducing agents as did anti-Gya and anti-Hy. In addition,
      similar to that found for anti-Gya and anti-Hy, anti Joa also showed reduced
      binding, as determined by haemagglutination and flow cytometric analysis, to
      erythrocytes from patients with paroxysmal nocturnal haemoglobinuria. Immune
      precipitates prepared from radio-iodinated antigen-positive red cells with anti
      Joa, anti-Gya and anti-Hy gave similar results--a major component of M(r) 49,000
      60,000 (the Gya/Hy-active glycoprotein) and a second component of M(r) 85,000
      92,000 (this may be a dimer of the Gya/Hy-active glycoprotein, or a
      coprecipitated protein). These immune precipitates, when probed with both anti
      Gya and anti-Hy under non-reducing conditions, gave a positive immunoblotting
      reaction to both the M(r) 49,000-60,000 and the M(r) 85,000-92,000 components.
      These results strongly suggest that the Joa antigen is expressed on the same
      glycoprotein that carries the Gya and Hy antigens.

PMID- 8146988
TI  - Screening of F.VIII:C antibodies by an enzyme-linked immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay (Elisa) method was developed in order to
      examine prevalence and titer of antibodies directed against the factor VIII
      coagulant protein (F.VIII:C) in hemophilia A and nonhemophilia A patients. Highly
      purified F.VIII:C was used as immunosorbent on microtiter plates with a
      peroxidase-conjugated goat anti human IgG antibody for F.VIII:C antibody
      detection. Results determined by Elisa were compared with measurements according
      to the Bethesda method. Initially 24 plasma samples containing an F.VIII:C
      inhibitory activity ranging from 0 to 7,700 Bethesda units (BU) were analysed. At
      plasma dilutions of 1:128 the optical density determined by our Elisa measurement
      and the corresponding BU showed a logarithmic correlation. The coefficient of
      correlation was r = 0.92 with a standard deviation of 0.002 from the regression
      curve. Plasma samples were analysed from 53 hemophilia A patients, from 21
      nonhemophilia patients with acquired F.VIII:C antibodies and from 460 randomly
      selected nonhemophilia patients presenting for routine preoperative coagulation
      examination. F.VIII:C antibody-positive Elisa results and positive BU were found
      in 7 hemophilia A patients and the 2 patients with a history of acquired F.VIII:C
      antibodies. Positive Elisa results and negative BU were found in 1 hemophilia A
      patient and 25 out of 460 nonhemophilia A patients (5.43%) suggesting F.VIII:C
      antibodies without inhibitory potency on F.VIII:C in these cases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8146989
TI  - Hepatitis C virus infection. An endemic area in north Italy.

PMID- 8146990
TI  - Evaluation of different supplementary assays for the confirmation of HIV-1 and
      HIV-2 infections.

PMID- 8146991
TI  - A rapidly fatal case of immune haemolytic anaemia due to cefotetan.

PMID- 8146992
TI  - Economic donor screening for anti-HIV in the developing world.

PMID- 8146993
TI  - Tumour imaging with radiolabelled monoclonal antibodies.
AB  - The specificity of nuclear medicine techniques for imaging cancer is improved by
      characterization of the cancer cell as different from the normal.
      Radioimmunoscintigraphy, imaging with radiolabelled antibodies and
      radioimmunotherapy, using beta emitting radionuclides, are developing to give
      specific cancer identification and treatment. The new approaches include genetic
      engineering of humanized antibody constructs for imaging and bifunctional
      antibody like molecules for a two stage approach to radioimmunotherapy. There is
      an important clinical role for current radioimmunoscintigraphy with 99Tcm
      Technetium as the signal.

PMID- 8146994
TI  - [Germ cell tumors of the testis].
AB  - Testicular cancer is the most common malignancy in men aged 15 to 30 years. In
      the 1990s testicular cancer has become one of the most curable solid neoplasms,
      and it can serve as a paradigm for the multimodal treatment of solid
      malignancies, making even a metastasized cancer a curable disease. The dramatic
      improvements in survival have occurred as a result of the combination of
      effective diagnostic techniques, improvement in serum tumour markers,
      modification of surgical technique and, above all, the development of highly
      effective multidrug chemotherapeutic regimens based on cisplatin. In the 1990s
      overall survival for all stages of testicular cancer should be well above 80% and
      should approach 100% for patients with low stage disease. Important studies
      forming the basis for the most up to date multimodality treatment are reviewed in
      this article. Alternative strategies for salvage therapy in poor risk patients
      and those who failed to respond to treatment are discussed, as well as
      minimization of toxicity in low risk patients.

PMID- 8146995
TI  - [Possible applications of laser in otorhinolaryngology].
AB  - Laser therapy in otolaryngology--head and neck surgery using laser types working
      in the range of the visible and infrared part of the electromagnetic spectrum is
      well established. The laser types usually employed for micro- and macrosurgery of
      the aero-digestive tract and for microsurgery of the middle ear, involving
      thermal ablation of tissue and extensive areas of damage are described, as well
      as recent advances in laser technology for future use. The mechanisms by which
      non-thermal, photo-ablative pulsed solid-state crystal infrared and UV-excimer
      lasers and photodynamic therapy affect biological tissues are reported. The
      advantageous main areas of application of the different types of laser according
      to their physical properties are compared on the basis of the results of our own
      studies and the relevant literature.

PMID- 8146996
TI  - [Changes in selenium status, antioxidant enzyme activity and lipid peroxide level
      after drinking cures in Bad Hall health resort].
AB  - 61 spa patients, predominantly with heart and vascular diseases, were divided
      into 2 therapeutic groups. In addition to the usual balneotherapeutic program,
      one group (J) received a course of "iodine brine concentrate" for drinking (2 x
      100 ml, daily iodine uptake approximately 9 mg), and the control group (CI)
      received isotonic NaCl in the same way. The patients were mostly on a reduced-fat
      and -calorie diet. The following parameters were determined at the beginning and
      at the end of the 26-day treatment period: total cholesterol, HDL-cholesterol,
      triglycerides, lipoprotein (a) (in serum); selenium (Se), malondialdehyde (MDA),
      and activities of Se-dependent, Se-independent, and total glutathione peroxidase
      (GSH-PX) (in plasma). In the J group, a significant increase was found in Se
      independent (+17%) and total GSH-PX (+5%) and a significant decrease in total
      cholesterol (-6.9%) and MDA (-13.2%). At the end of the cure, Se levels were
      higher in the J group than in the C1 group. The only significant change in the C1
      group was a decrease in HDL-cholesterol. Positive correlations were found between
      selenium and Se-dependent GSH-PX (r = 0.253) and between total GSH-PX and Se
      dependent GSH-PX (r = 0.665). A negative correlation was obtained between Se
      dependent and Se-independent GSH-PX (r = -0.331). The results are discussed with
      regard to the importance of antioxidant defense mechanisms in several
      degenerative diseases (atherosclerosis, diabetes, cataract etc.), and also
      respecting interactions between iodine and selenium metabolism, as well as
      normalization effects conditioned by the balneotherapy itself.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8146997
TI  - [Responsible prescription of hearing aids].
AB  - A case report serves to document that sufficient cerebral circulation is
      mandatory for sustaining function of the brain. If impulses from the ear are not
      processed within the areas of the brain normally doing this, prescription of a
      hearing aid will not improve the capacity to perceive in a patient being hard of
      hearing. In these cases, one should rather examine the state of the cerebral
      circulation.

PMID- 8146999
TI  - [Modern section imaging center is opened at the Linz Wagner Jauregg District
      Neurologic Clinic].

PMID- 8146998
TI  - [Hormone substitution in patients after primary treatment of gynecologic
      malignancies].
AB  - Hormone replacement therapy for postmenopausal patients following primary
      treatment of gynecologic malignancies has changed considerably during recent
      years. Estrogens have been found useful to prevent osteoporosis and
      cardiovascular disease as well as to ameliorate symptoms of estrogen deprivation.
      Thus, hormone replacement therapy can improve life quality of patients. Estrogen
      gestagen replacement therapy after primary treatment of endometrial cancer is no
      longer contraindicated, at least in stage Ia to Ib disease. For breast cancer
      patients, the German Society of Senology has published recommendations based on
      the receptor status and lymph node status of an individual patient. Exogenous
      estrogens and gestagens are not contraindicated for breast cancer patients with
      negative receptors and negative lymph nodes. However, tamoxifen is indicated for
      patients with positive receptors and positive lymph nodes. If symptoms of
      hormonal deprivation occur, gestagens may be added to tamoxifen in these
      patients. There are no contraindications for hormone replacement therapy in
      patients with malignant tumors of the ovary, fallopian tube, cervix, vagina, and
      vulva.

PMID- 8147000
TI  - [Medicine in crisis].

PMID- 8147001
TI  - [Health economics of early summer meningoencephalitis in Austria. Effects of a
      vaccination campaign 1981 to 1990].
AB  - Tick-borne encephalitis (TBE) was until the early 1980s among the most frequent
      causes of viral induced central-nervous infectious diseases in Austria. Since
      1981 the vaccination was forced by intensive media campaigns. Aim of this study
      was to investigate the effects of the media campaigns and to evaluate them under
      health economic criteria. The number of hospitalized TBE-cases declines from 1981
      to 1990, the linear trend shows a reduction from 427 to 109. If the linear trend
      from 1971 to 1980 would have continued the respective number in 1990 would have
      been 585 cases. Thus the model shows that from 1981 to 1990 more than 50% or
      2,690 out of 5,368 possible cases are prohibited, from 1991 to 2000 based on the
      1990 vaccination rate approximately 85% or 500 cases annually. In the age group 7
      to 14 years the proportion of protected exposed is almost 97%. The loss of
      quality of life is higher than represented by the inpatient statistics. Many of
      the TBE victims have chronic impairments, mainly due to paresis and depression.
      Based on the 1990 cost data economic benefits for the social insurance companies
      in the decade 1981 to 1990 are AS 147 millions for inpatient care, respectively
      AS 108 millions for loss of productivity and AS 77 millions for early retirement,
      resulting in total benefits of AS 331 millions. The estimated benefits for 1991
      to 2000 based on 1990 cost data are AS 270 millions for inpatient care, AS 200
      millions for loss of productivity, and AS 368 for early retirement (total AS 828
      millions).

PMID- 8147002
TI  - [Integrated physical therapy in psychiatry, neuro-rehabilitation and
      rehabilitation of the aged].
AB  - Physiotherapy forms a main part of modern therapy, however it only can be optimal
      in full integration with pharmacotherapy, psychotherapy and sociotherapy.
      Gerontopsychiatry offers a large field for physiotherapists. Besides highly
      specialised physiotherapy the dimension of recreation, fun-giving and
      amelioration of life quality must not be forgotten in physiotherapy. These
      possibilities from an important function within a human and humanitarian
      medicine. A further main condition for amelioration is to involve relatives fully
      in the therapeutical concept. Our experience has shown that within the domestic
      surrounding rehabilitative progress can well arrive; however, only if
      systematically prepared and uninterrupted stimulated.

PMID- 8147003
TI  - [The death of Schiller].

PMID- 8147004
TI  - [What is the future of antiviral therapy of HIV-infected patients? Reports of
      results of antiretroviral therapy studies at the IX. World Congress on AIDS in
      Berlin].

PMID- 8147005
TI  - [Euthanasia--expression of human freedom or inability to guarantee human
      dignity?].

PMID- 8147006
TI  - [Left ventricular hypertrophy and its regression. Effects of antihypertensive
      medication in animal model and patient].

PMID- 8147007
TI  - [Etiology and pathogenesis of acute pancreatitis].

PMID- 8147008
TI  - [Etiopathogenesis, morphology and hemodynamics of portal hypertension].

PMID- 8147009
TI  - [Iodine deficiency still exists in East Germany].

PMID- 8147010
TI  - [Modern wound dressings. Part 4: Hydrocolloids].

PMID- 8147011
TI  - [Diagnostic errors in laboratory findings].

PMID- 8147012
TI  - [From the general practice of expert assessment: oversight of a lumbar vertebral
      fracture].

PMID- 8147013
TI  - [A case from general practice (14): isolated splenomegaly].

PMID- 8147014
TI  - ["By nature I am not a subtle product...": On the 500th birthday of Philippus
      Aureolus Theophrastus Bombastus von Hohenheim, called Paracelsus].

PMID- 8147015
TI  - [Indications for long-term electrocardiography].

PMID- 8147016
TI  - [Perioperative safety and anesthesiologic monitoring].

PMID- 8147017
TI  - ["Prognostic factors" in breast cancer--1].

PMID- 8147018
TI  - [Hyperthermia in cancer therapy].

PMID- 8147019
TI  - [Familial colorectal polyposis--a case report].

PMID- 8147020
TI  - [Pharmacologic treatment of urinary incontinence in the elderly].

PMID- 8147021
TI  - [Sex counseling of female paraplegic patients].

PMID- 8147022
TI  - [The history of natural and artificial sweetening agents].

PMID- 8147023
TI  - [Modern wound dressings. 5: Foam dressings].

PMID- 8147024
TI  - [Robert Koch and bacteriological technique].

PMID- 8147025
TI  - [What is the status of immune prevention of "tick bite diseases"?].

PMID- 8147026
TI  - [Infectious diarrheal diseases caused by bacterial pathogens--pathogenesis,
      diagnosis and therapy].

PMID- 8147027
TI  - [Incidence of Borrelia burgdorferi in scale ticks Ixodes ricinus (Acari:
      Ixodidae) in the Brandenburg district].

PMID- 8147028
TI  - [Questions and answers on the epidemiology and etiology of goiter].
AB  - Goitre defines any enlargement of the thyroid independent of its cause. Worldwide
      iodine deficiency is the single most common cause of a goitre. However, before
      iodine deficiency is established, other thyroid diseases need to be ruled out.
      Very rarely increased production of TSH (secondary hyperthyroidism) or of
      hormones with TSH activity (e.g. hCG producing tumours), inborn errors of iodine
      metabolism, and defects of the thyroid hormone receptor (thyroid hormone
      resistance) are the cause of a goitre. Furthermore, malignancy of the thyroid and
      autoimmune disease (e.g. Grave's disease) may lead to a thyroid enlargement.
      Still, worldwide more than 90% of the 200 million patients with goitre suffer
      from iodine deficiency. In Germany, as in only few other European countries which
      lack any nation-wide prophylactic iodine supplementation, goitre is endemic with
      a prevalence of about 25%. The classical concept on the mechanism of iodine
      deficiency induced goitre is based on decreased thyroid hormone synthesis in the
      presence of iodine depletion, which leads to increased production of TSH,
      stimulating thyroidal growth. Recent in vitro findings using thyroid cell
      cultures expand this concept by demonstrating that TSH regulates the
      differentiation and function of thyroid cells and may induce hyperplasia, but not
      cell proliferation. In contrast to TSH, the locally produced growth factors IGF I
      (insulin-like growth factor I) and EGF (epidermal growth factor) stimulate
      thyroid cell proliferation. Intrathyroidal iodine antagonises the effects of IGF
      I and EGF and simultaneously stimulates transforming growth factor beta (TGF
      beta), which inhibits thyroid cell proliferation. Thus, intrathyroidal iodine
      appears to regulate thyroidal growth by controlling proliferation stimulating
      (IGF I, EGF) and proliferation inhibiting (TGF-beta) growth factors. Though these
      new insights fill several gaps of the classical concept on the pathogenesis of
      endemic goitre, open questions remain.

PMID- 8147029
TI  - [Management of the cold thyroid nodule and thyroid malignancy].
AB  - The evaluation and management especially of cold thyroid nodules remains an area
      of controversy. The past decade has witnessed two important advances. The
      increased availability of fine-needle aspiration of thyroid nodules has altered
      the clinician's approach to this disease, and provides for the single most
      precise method for selecting appropriate patients for surgery. The introduction
      of high-resolution thyroid ultrasonography provides for anatomic definition that
      is clearly superior to thyroid scintigraphy. However, radionuclide imaging
      remains critical for determining the functional status of abnormal thyroid
      tissue. This review attempts to provide a practical approach to the evaluation
      and management of the thyroid nodule. Only rare data exists concerning the
      therapeutic approach of cold thyroid nodules and non-toxic nodular goitre. There
      seems to be a size-reducing effect by thyroxin-treatment, but no data are
      reported from iodine deficient areas. Concerning the treatment of differentiated
      thyroid carcinoma total thyroidectomy combined with eradication of remaining
      thyroid tissue with iodine 131 is usually preferred. In case of smaller or occult
      carcinoma various modes of uni- or bilateral subtotal resection are used.
      Chemotherapy is of little use in treating differentiated thyroid carcinoma and
      remains as a last possibility if usual approaches are no longer effective. To
      control local-invasive growth of anaplastic thyroid carcinoma combined treatment
      with mitoxantrone and hyperfractionated irradiation seems to be a successful
      approach.

PMID- 8147030
TI  - [Inflammatory thyroid diseases].
AB  - Thyroiditis are common causes of the goitrous enlargement of the thyroid, and
      comprise a number of inhomogeneous disorders. The only criterion they have in
      common is an inflammatory infiltration of thyroid tissue. The following diseases
      belong to this group: Hashimoto's thyroiditis, thyroiditis de Quervain, acute
      thyroiditis, Riedel's thyroiditis and rare forms of thyroiditis. These diseases
      are reviewed with regard to incidence, etiology, pathogenesis, clinical features,
      diagnosis and treatment.

PMID- 8147031
TI  - [Drug therapy of goiter. Iodine, thyroid hormones or combined therapy].
AB  - Recent in vitro and in vivo data indicate that intrathyroidal iodine deficiency
      is the most important factor for the development of endemic goitre. Normalisation
      of the thyroid iodine content is essential to achieve regression of hyperplasia
      of iodine-depleted thyroid tissue. As clinical studies clearly demonstrate iodine
      should always be part of therapy of euthyroid diffuse endemic goitre. After
      therapy with levothyroxine alone the intrathyroidal iodine deficiency remains
      unchanged, and relapse of goitre will soon occur. There are the following
      indications for conservative therapy of euthyroid diffuse endemic goitre: 1.
      Children and adolescents should be treated by iodine alone (100-200
      micrograms/die). 2. For adults a combined therapy with levothyroxine (100
      micrograms/die) plus iodine (200 micrograms/die) is to be preferred to avoid the
      possible induction of thyrotoxicosis or autoimmune thyroid disease by high iodine
      doses (monotherapy with iodine would need 400-500 micrograms/die). In addition no
      reduction of goitre volume can be expected in adults older than 40 years because
      of an increasing number of thyroid nodular formations. 3. During pregnancy the
      combination therapy has advantages as high iodine dosages of iodine, potentially
      dangerous for the foetus, can be avoided whereas goitre formation in the mother
      is effectively suppressed and iodine deficiency in mother and child is
      compensated. Goitre therapy should be carried out at least for 6 months. The
      efficacy of goitre therapy should be controlled by sonographic determination of
      thyroid volume at least once a year after the end of treatment. An effective
      goitre prophylaxis with 100-200 micrograms iodine per day is recommended
      following the actual therapy period.

PMID- 8147032
TI  - [HDL subfractions in post-prandial lipidemia].
AB  - The influence of a standardised fatty test meal on the composition of high
      density lipoprotein (HDL) subfractions (HDL3, HDL2) and the concentration of
      other lipid parameters was investigated in a group of young women of the age 20
      25 years, in women of the age range 60-90 years, and in a group of patients with
      arteriosclerotic diseases. Total cholesterol and HDL cholesterol in serum do not
      change significantly under extreme conditions of postprandial lipaemia. This is
      true also regarding persons in high age groups and patients with arteriosclerotic
      diseases. In contrast to the group of young subjects, 60-90 years old women show
      both elevated HDL triglyceride levels under basal conditions and a greater
      magnitude of HDL triglyceride enrichment under the conditions of postprandial
      lipaemia. Patients with arteriosclerotic diseases also exhibit a marked
      postprandial HDL triglyceride enrichment. It is concluded that there are
      metabolic relations between the observed low HDL2 cholesterol concentrations in
      the group of older subjects and in patients with arteriosclerotic diseases and
      the high magnitude of HDL triglyceride increase in the postprandial state which
      are relevant within the risk syndrome hypertriglyceridaemia-low HDL2 levels.

PMID- 8147033
TI  - [Reversibility of dementia in hypothyroidism].
AB  - Thirteen percent of all dementia disorders are potentially reversible.
      Hypothyroidism is among the most frequent causes of reversible dementias.
      Although it is generally accepted that dementia symptoms in hypothyroidism can be
      significantly reduced, many questions about the therapeutic efficacy are
      unexplained. It has not been systematically investigated which psychopathological
      symptoms respond well to thyroid hormone substitution, how long the treatment
      should last and whether duration of symptoms or severity of dementia have an
      influence on the degree of remission of psychopathological impairment. We
      investigated these questions in two prospectively studied cases with dementia in
      hypothyroidism.

PMID- 8147034
TI  - [Systemic diseases--the significance of early diagnosis exemplified by systemic
      lupus erythematosus and Wegener's granulomatosis].
AB  - New therapeutic modalities have shown remarkable advances in the fields of
      systemic lupus erythematosus and Wegener's granulomatosis. For an optimal
      clinical outcome therapy has to be started early and must be adapted to disease
      activity. Concerning these two points early diagnosis is essential. This aim can
      be reached by a detailed evaluation of the patient's history by focusing on early
      symptoms and on typical clinical constellations, taking into account that both
      diseases show a great variability and sometimes even an insidious course.
      Immunological tests, capillary microscopy, echocardiography and computed
      tomography can be very helpful in the diagnosis of these diseases.

PMID- 8147035
TI  - [Axial hiatal hernia--correlation of motility disorders and pathological reflux
      in the esophagus in patients with and without reflux esophagitis].
AB  - Hiatal hernia is a very common finding in esophagogastroduodenoscopy (EGD). Only
      some patients with hiatal hernia suffer from gastroesophageal reflux disease
      (GERD), defined by pathological 24-h-pH-metry, while almost all patients with
      GERD do have hiatal hernia. To work out the differences in possible motility
      disorders and in a pathologic acid reflux we examined 92 patients with hiatal
      hernia by means of manometry and 24-h-pH-metry of the esophagus. A motility
      disorder of the tubular esophagus in the patients with GERD (with or without
      reflux esophagitis) was significantly more common than in patients without GERD
      (p = 0.006). In most cases it was an esophageal hypomotility. There is no
      significant difference in the basal pressure of the lower esophageal sphincter
      (LES) between the two groups. We conclude that besides other factors which impair
      esophageal clearance function a motility disorder of the tubular esophagus is the
      main cause for the development of GERD in the patients with hiatal hernia. A
      lowered pressure of the LES seems not to play a major role in the etiology of
      reflux esophagitis.

PMID- 8147036
TI  - [Liver complications in HELLP syndrome].
AB  - In a 5 years period 5 female patients suffering from a severe HELLP syndrome were
      treated. The problems concerning diagnostic and treatment are discussed. 3
      patients had to be operated on in an emergency state. The operations were
      performed because of acute and severe abdominal bleeding. Two of the patients
      needed liver transplantation as an emergency procedure, one of them died after
      hepatectomy on the list. Another one died 7 weeks after successful
      transplantation in a state of prolonged sepsis. The two conservatively treated
      and the one transplanted patient are still alive and well.

PMID- 8147037
TI  - [Barrett esophagus with severe epithelial dysplasia--always surgery? A case
      report].
AB  - A 57 year-old patient presented with a Barrett's epithelium over the length of 18
      cm. We found the typical functional changes of acid reflux and hypomotility in
      the distal esophagus. There was a history of chemotherapy for seminoma 30 years
      ago. Because of the repeated finding of severe dysplasia surgery was proposed.
      The patient died in the postoperative period with the signs and symptoms of
      pulmonary embolism. There was no invasive tumor found in the resected part of the
      esophagus. Main aspects of the etiology and histological characterism of
      Barrett's esophagus and the indication for surgery in cases with severe dysplasia
      are discussed.

PMID- 8147038
TI  - Acceptance and outcome of endoscopic screening for colonic neoplasia in patients
      undergoing clinical rehabilitation for gastrointestinal and metabolic diseases.
AB  - Our purpose was to study the acceptance and the outcome of endoscopic screening
      investigations of the colon in patients between 50 and 60 years of age in a
      clinical rehabilitation center. A total of 1,166 patients (m = 691, f = 475)
      entered the study. After guaiac testing all patients for fecal occult blood loss
      (FOBT), 667 patients (57%; m = 407, 61%; f = 260, 39%; n.s.) accepted a
      sigmoidoscopy. Of 658 (m = 403, f = 255) patients with complete investigation,
      153 (23%) (m = 104, 26%; f = 49, 19%; n.s.) had a total of 272 neoplastic polyps,
      including 1 carcinoma. Adenomas = /> 10 mm were found exclusively in male
      patients (n = 25, p < 0.001). In comparing patients aged 50-55 years (n = 386)
      with those aged 56-60 years (n = 272), prevalences of neoplasia were found to be
      19%/29% (p < 0.01), and prevalences of adenomas = /> 10 mm were 2%/10% (p <
      0.05). The acceptance of a colonoscopy in patients with neoplastic polyps at
      sigmoidoscopy was 116/153 (m = 78, 75%; f = 38, 78%; n.s.). In 39 of these
      patients (34%) (m = 31, 40%; f = 8, 21%; p < 0.05), 68 further adenomas were
      detected but no carcinoma or adenoma with severe dysplasia. Multiple adenomas in
      the proximal colon were seen in 17 cases (15%) (m = 16, 21%; f = 1.3%; p < 0.01).
      The FOBT was positive in 10/658 patients, including the case with a carcinoma,
      but only in 4/25 with adenomas = /> 10 mm. In 5 cases with positive FOBT
      sigmoidoscopy and complementary colonoscopy did not reveal any pathology.

PMID- 8147040
TI  - [German Association for the Study of the Liver, 10th meeting. Heidelberg, January
      28-29, 1994. Abstracts].

PMID- 8147039
TI  - [Hypertrophic gastropathy, resembling Menetrier's disease, in transgenic mice
      with overexpression of TGF-alpha in the stomach].

PMID- 8147041
TI  - [Risk of recurrence in HELLP syndrome].
AB  - The recurrence risk of HELLP-syndrome is reported to be between 2.6% and 24%. But
      yet, there are no accurate case reports about this topic available. In a
      retrospective study, 25 patients, which had suffered from a pre partum HELLP
      syndrome, were interviewed about possible subsequent pregnancies. In 7 patients 8
      pregnancies were found, which began between 5 and 55 months after the HELLP
      syndrome. No recurrence of a HELLP-syndrome was observed in these 7 patients.
      Although in 71% a hypertension had been present during the HELLP-syndrome, only 1
      patient had an elevated blood pressure in the subsequent pregnancy. Whilst all of
      the patients with HELLP-syndrome had been delivered by cesarean section, 50% of
      the patients were delivered vaginally in the subsequent pregnancy. There was no
      evidence of maternal or neonatal complications related to HELLP-syndrome.
      Nevertheless, even if the recurrence risk seems to be low, pregnancies after
      HELLP syndrome should be observed carefully.

PMID- 8147042
TI  - [Various forms of hypertension in pregnancy and perinatal fetal condition].
AB  - A prospective study analyses the course of pregnancy and the delivery of 315
      women suffering from hypertension during their pregnancy. The perinatal state of
      the child is analysed as to the prevailing kind of hypertension. Gravidae
      suffering from gestation and chronical hypertensions, resp. (three forth of all
      kinds) delivered at birth term an eutrophic child. The proportion of spontaneous
      deliveries, acidosis morbidity, and of Apgar score was in correspondence with the
      average of all deliveries per annum without hypertension. The perinatal mortality
      among all kinds of hypertension was 1.6% caused only by children from gravidae
      suffering from preeclampsia and chronical nephropathy (corresponding to a quarter
      of all kinds). In comparison with gestation hypertension, chronical hypertension
      and the annual average of all deliveries, such gravidae prematurely delivered
      hypotrophic children of high acidosis morbidity and a worse Apgar score. Gravidae
      suffering from preeclampsia had an 80% abdominal delivery frequency. The
      prognosis of the child is made worse by appearance and severity of proteinuria.

PMID- 8147043
TI  - [Behavior of blood pressure and heart rate at rest and during standing in
      pregnancy].
AB  - This study was designed to answer three questions: 1. Is there a change in
      systolic blood pressure, diastolic blood pressure and heart rate during
      pregnancy? 2. Are there alterations of these parameters during standing? 3. Is
      there a relationship between mean arterial blood pressure and heart rate at rest
      and during standing? In a randomized study 161 clinically healthy pregnant women
      between 8th and 41st week of pregnancy were tested with a modified orthostatic
      test over defined time periods during pregnancy. Systolic and diastolic blood
      pressure and heart rate were registered in one minute intervals over a 30 minute
      period with an automatic Dinamap measuring device. This period was subdivided in
      a 10 minutes lying period, 10 minutes standing period followed by a 10 minutes
      lying period. There was a marked increase in systolic and diastolic blood
      pressure at rest with the beginning of the 34th week of gestation (p < 0.05 and p
      < 0.01). Despite this, maternal heart rate continued to rise over the whole
      course of pregnancy (p < 0.01). Furthermore, women with a fall in heart rate on
      standing were only seen in late pregnancy. Finally, pregnant women with a low
      mean arterial blood pressure (< or = 85 mmHg) did not experience a fall in blood
      pressure on standing more frequently than normal controls (> 85 mmHg). We
      conclude that a fall in blood pressure on standing is not dependent on blood
      pressure at rest during pregnancy.

PMID- 8147044
TI  - [Postpartum diagnosis of diabetes in pregnancy in fetal macrosomia--comparison of
      two examinations].
AB  - Disorders of carbohydrate metabolism in pregnancy are often associated with
      macrosome newborns. There are two methods with different approach for
      retrospective diagnosis of gestational diabetes (GDM): 1. maternal postnatal oral
      glucose tolerance test (ppoGTT), 2. determination of cord blood insulin for
      detection of fetal hyperinsulinism. The presented study deals with the question
      how often macrosomia is correlated with pathologic cord blood insulin
      respectively pathologic ppoGTT and if both methods select identical collectives.
      Cord blood insulin was determined by RIA in 154 newborns with birth weight over
      the 90th percentile (threshold 15 microU/ml). On the 2nd day p.p. oGTT was
      performed in 80 women without prenatal diagnosis of GDM (threshold 95, 165, 145,
      125 mg%). 37/154 (24%) newborns showed pathologic insulin values. 24/80 (30%)
      women had pathologic ppoGTT. In 30% of the cases pathologic results of cord blood
      insulin and ppoGTT selected different collectives: 17/66 pathologic ppoGTT with
      normal insulin values, 7/14 normal ppoGTT with pathologic insulin values. The
      only use of ppoGTT would fail in 50% of cases of GDM with proved fetal
      hyperinsulinism. The determination of cord blood insulin offers the opportunity
      of direct diagnostics on the child in contrast to maternal ppoGTT. For
      retrospective diagnosis of macrosomia due to disorders of carbohydrate metabolism
      determination of cord blood insulin should be given preference to oGTT in
      puerperium.

PMID- 8147045
TI  - Phenprocoumon therapy during pregnancy: case report and comparison of the
      teratogenic risk of different coumarin derivatives.
AB  - The case report is about an infant suffering from coumarin embryopathy and
      coumarin syndrome after its mother underwent phenprocoumon treatment (Marcumar,
      Falithrom) during pregnancy (until 26th week of gestation). Interestingly, a
      hearing disorder was diagnosed, which had never been described in context with
      this substance. The coumarin derivatives warfarin, acenocoumarol and
      phenoprocoumon were compared with regards to spontaneous abortion rate, perinatal
      mortality and teratogenic risk. Eye anomalies or malformations seem to appear
      only under warfarin treatment, whereas CNS-malformations are more frequent under
      phenprocoumon. As a consequence, phenprocoumon treatment of fertile women seems
      rather doubtful. Upon discovery of a pregnancy under coumarin treatment, vitamin
      K should immediately be substituted in order to minimize the risk of anomalies
      and malformation.

PMID- 8147046
TI  - [A knowledge-based system for the interpretation of pelvimetric findings].
AB  - Digital Image Intensifier Radiography (DIR) as well as Nuclear Magnetic Resonance
      Tomography (NMR) using an especially developed imaging routine for pelvimetry are
      suitable tools for the assessment of the anatomical conditions when mechanical
      problems are supposed to occur during birth (cephalopelvic disproportion, breech
      presentation). A concept for an optimised evaluation procedure of these imaging
      techniques has been developed, including: a more elaborate measuring protocol,
      easily and precisely executable due to appropriate software packages being
      implemented in the diagnostic units, calculation of obstetrically relevant
      parameters not deriving immediately from the imaging procedures. This is possible
      by means of multiple regression analysis of a data base from 467 evaluated female
      pelvis computed tomograms, calculation of intrapelvic soft tissue place
      requirements by means of correlative analysis of female computed tomograms and
      weight-/height-index, empirical determination of cut off values in borderline
      pelvi-fetometric constellations evaluating 190 births by means of logistic
      regression of the according pelvic-fetometric data. The calculations necessary to
      obtain all these parameters are implemented in a software package which also
      contains an algorithm for the general characterisation of an individual pelvis.
      Thus, a rather sophisticated knowledge base for pelvic assessment becomes easily
      accessible.

PMID- 8147047
TI  - [Is premature labor weather-dependent? Correlation of premature labor with
      meteorologic data].
AB  - A preselected cluster of births (12351-4719 = 7632 = n) which was divided into 3
      groups (delivery between 28-32 gestational weeks, 33-37 gestational weeks and >
      37 gestational weeks) has been correlated with six major weather situations of
      the four meteorologically defined seasons. The correlation was made with the date
      of birth and with one day as well as two days before. The duration of pregnancy
      was longer by an average of 0.45 weeks (i.e. 3 days) when the major weather
      situation did not change for more than 8 days. The group with delivery 28-32
      weeks is more sensitive to meteorological influences than the group with delivery
      33-37 weeks. During cyclonic as well as during anticyclonic atmospheric drifts
      the groups 28-33 wks and 33-37 wks have been statistically over-represented. As
      far as the season is concerned over-representation is found in autumn. We
      conclude that pregnancies at risk of premature delivery should be followed up in
      short intervals during cyclonic and anticyclonic atmospheric drifts especially
      during the autumn season.

PMID- 8147048
TI  - [Color Doppler ultrasound in differential diagnosis of unilateral congenital
      cystic kidney abnormalities].
AB  - Doppler-sonography was performed in 16 newborns with prenatally diagnosed
      unilateral cystic renal malformation. 11 babies with multicystic dysplastic
      kidneys showed doppler-sonographically reduced systolic flow velocities and
      elevated resistive index (RI) [RI = 90-100%] or lack of obtainable perfusion
      signals. 4 of them had to undergo nephrectomy, the other asymptomatic patients
      could be managed conservatively, spontaneous regression could be observed. 5
      other infants suffering from cystic nephroma, severe ureteropelvic junction
      obstruction, hudge bleeding of the adrenal gland and hydronephrosis due to
      ectopic ureter, having been prenatally presented as "cystic renal malformations",
      initially showed normal systolic flow velocities within renal parenchyma and only
      slightly elevated RI (mean = 83%). By this they could be differentiated from
      multicystic kidney dysplasia. We therefore propose to use doppler-sonography for
      differential diagnosis of prenatally assumed cystic kidney malformations.

PMID- 8147049
TI  - [Benign tumors of the heart].
AB  - Benign tumors of the heart are rare and their symptomatology often remains
      ambiguous. Nevertheless, they are an important differential diagnosis of valvular
      heart disease, cardiac insufficiency, ventricular and supraventricular rhythm
      disturbances, conduction defects, syncopes, and arterial or pulmonary embolism.
      Furthermore, they can mimic an infective, malignant or immunological disease. For
      the first time, at the beginning of the 1950s, the clinically suspected diagnosis
      of a cardiac tumor was confirmed by angiocardiography; now, after the technical
      evolution of ultrasound, computer-tomography and nuclear magnetic resonance
      imaging over the past 30 years, the intravitam diagnosis is made more often and
      patients can be surgically treated.

PMID- 8147050
TI  - [Torsade de pointes].
AB  - Torsade de pointes (TDP) is a polymorphic ventricular tachycardia with a
      particular electrocardiographic pattern of continuously changing ("twisting")
      morphology of the QRS complex occurring in the setting of delayed myocardial
      repolarization (i.e., prolongation of the QT interval). TDP may develop in the
      setting of an idiopathic disorder (Jervell/Lange-Nielsen syndrome, Romano-Ward
      syndrome, sporadic long QT syndrome) or may be induced by pharmacologic agents
      which prolong the QT interval, as well as by other clinical circumstances under
      which repolarization is delayed (e.g., hypokalemia, hypomagnesemia, bradycardia)
      (acquired long QT syndrome). Since the treatment of TDP strongly differs from
      that of conventional ventricular tachycardia, correct diagnosis is critical as it
      guides the treating physician in selecting the appropriate mode of therapy. In
      this paper mainly the electrocardiographic criteria presently used for the
      correct identification of this unusual form of ventricular arrhythmia are
      presented. Additionally, the potential mechanisms and therapeutic modalities of
      TDP are discussed.

PMID- 8147051
TI  - [Do heart transplant patients benefit from rate-adjusted electrostimulation?].
AB  - Exercise capacity of heart transplant recipients is limited in comparison to
      normals and, due to cardiac denervation, exercise-induced heart-rate response is
      blunted in these patients. In order to evaluate the effect of rate-responsive
      atrial pacing on exercise capacity, 13 patients (three female, 10 male; age: 53
      +/- 7 years) were studied 2-35 months after orthotopic heart transplantation.
      Spiroergometry with breath-to-breath gas analysis was performed during a
      progressive supine bicycle test with a starting workload of 25 watts and
      increments of 15 watts every minute. In comparison to 10 normals (two female,
      eight male; age: 51 +/- 7 years) maximal heart rate (127 +/- 17 vs. 146 +/- 12
      min-1), maximal work load (107 +/- 27 vs. 208 +/- 42 watts) and oxygen
      consumption at the anaerobic threshold (9 +/- 2 vs. 18 +/- 4 ml/kg/min) were
      significantly reduced in heart transplant recipients (p < 0.05). During the
      exercise test the p-waves of the remaining part of the recipients' atria were
      registered via a transoesophageal catheter. The maximal rate of the innervated
      recipients sinus node (146 +/- 15 min-1) was equal to the maximal heart rate of
      the control group. The exercise protocol was repeated during atrial stimulation
      of the transplanted hearts. To achieve a physiological adaptation of the heart
      rate, the pacing rates were adjusted to the rates of the recipients sinus node.
      In comparison to the previous tests an improvement of cardiopulmonary exercise
      capacity was not observed during rate adaptive pacing.

PMID- 8147052
TI  - In vivo quantification of myocardial echo intensity from logarithmically
      amplified, demodulated radiofrequency signals.
AB  - Clinical application of echocardiographic tissue characterization necessitates
      measurements through the chest wall. Different distances between transducer and
      myocardial region of interest result in variable attenuation effects. Therefore,
      meaningful comparisons of myocardial echo intensity measurements are difficult
      with current equipment. The present study aims at the quantification and
      compensation of depth-dependent attenuation effects. Ten normals, 14 patients
      with mild (n = 7) or moderate (n = 7) hypertensive left ventricular hypertrophy
      and 10 transplant candidates were examined. Gain-independent logarithmically
      amplified, demodulated radiofrequency signals of parasternal long axis cross
      sections were digitized. Mean myocardial echo intensities were determined in
      septal and posterior wall regions of interest. The slope of attenuation was
      determined from these clinically obtained data by plotting the distances between
      transducer and regions of interest against myocardial echo intensities. An
      attenuation coefficient derived from this slope was used for compensation of the
      depth-dependent losses of myocardial echo intensity. Compared with normals,
      compensated mean myocardial echo intensities were significantly lower in mild or
      moderate hypertensive left ventricular hypertrophy, but showed no significant
      difference in transplant candidates. Despite several limitations, the method
      employed in this study appears to be a possible approach to in vivo
      quantification and compensation of attenuation.

PMID- 8147053
TI  - [Planimetric quantification of aortic valve stenoses using multiplanar
      transesophageal echocardiography].
AB  - Standard techniques used in order to quantify the severity of aortic valve
      stenoses in clinical practice comprise: transthoracic echocardiography, namely,
      by determining maximum and mean transvalvular gradients and evaluating aortic
      valve areas, as well as invasive techniques which quantify aortic valve areas
      through hemodynamic pressure measurements and application of the Gorlin formula.
      Since the introduction of the multiplane TEE technique, it has become feasible to
      scan the aortic valve in a strictly horizontal plane and quantify the aortic
      valve orifice by planimetry. In this study, we investigated 23 patients with
      various degrees of aortic valve stenoses. We compared aortic valve areas, which
      had been planimetrically determined by multiplane TEE scans, and mean aortic
      valve gradients (standard TEE technique) with pressure gradients and valve areas
      derived from hemodynamic measurements obtained during cardiac catheterization,
      and have found that the valve areas as well as the mean pressure gradients
      correlate well.

PMID- 8147055
TI  - [Bilateral coronary-pulmonary artery fistula and accessory vascular connection of
      the thoracic aorta to the right lower pulmonary artery].
AB  - A 41-year-old man presenting with atypical chest pain was admitted to hospital
      with suspected pericarditis after a common cold disease. A complex risk profile
      for arteriosclerotic coronary artery disease was taken into account in
      differential diagnosis. Cardiac catheterization revealed large bilateral coronary
      artery-pulmonary artery fistulas as well as an accessory vessel with origin of
      the thoracic aorta both draining into the lower right pulmonary artery. The
      vessel anomalies showed a remarkable plexus-like morphology before entering into
      the pulmonary artery. Arteriosclerotic coronary artery disease was not found. No
      evidence of myocardial ischemia was found in the furthermore asymptomatic
      patient, therefore surgical correction of the vessel anomalies was not performed.
      To our knowledge the present case report represents the first case with bilateral
      coronary artery-pulmonary artery fistulas and an accessory communication of the
      thoracic aorta to the pulmonary artery vasculature.

PMID- 8147054
TI  - [Contrast echocardiography in the evaluation of myocardial flow reserve].
AB  - In order to determine whether changes in myocardial perfusion can be assessed by
      myocardial contrast echocardiography, intracoronary injections of 2 ml of
      sonicated iopromid were performed before and 30 to 45 s after application of
      papaverine in 31 patients (mean age 58 years). 13 patients showed coronary artery
      disease (KHE), 6 patients hypertensive heart disease (HHE), and 12 patients had
      no proven heart disease (KTR). Contrast decay-halftime (T/2), maximal video
      intensity (Imax) and area under the curve (Area) were derived by computer
      assisted videodensitometry. After papaverine KTR showed a significant increase of
      T/2 (from 5.1 +/- 1.5 to 6.8 +/- 3.2 s, p < 0.05), of Imax (from 36 +/- 13 to 52
      +/- 16 E, p < 0.002) and of Area (from 203 +/- 95 to 379 +/- 188 E*s, p < 0.002)
      compared to baseline values. In this group the ratios of hyperemia to baseline
      flow conditions were 1.5 +/- 0.4 (from 1.0 to 2.4) for Imax and 1.9 +/- 0.9 (from
      1.1 to 3.9) for Area. In HHE and KHE, hyperemia induced no significant changes of
      T/2, Imax and Area. Heart rate was increased by 4.3% and mean aortic pressure was
      decreased by 6.2% in all groups after papaverine. Double-product was not altered
      significantly in any group. Myocardial contrast echocardiography revealed a
      significant increase in variables of contrast wash-out curves only in patients
      without proven heart disease. In contrast, no relevant changes of T/2, Imax and
      Area on average were observed in patients with coronary and hypertensive heart
      disease. Thus, myocardial contrast echocardiography seems to be suitable to
      document a reduced papaverine vasodilator response in these patients.

PMID- 8147056
TI  - [Single coronary artery with branching of the right coronary artery from the left
      atrioventricular ramus of the circumflex artery. Incidence and significance].
AB  - In a series of 8500 consecutive coronary angiographies, we found three times an
      "anatomic single coronary artery" with origin of the right coronary artery from
      the AV-branch of the dominant circumflex artery (incidence 0.035%). In all three
      patients the investigation was made because of the suspicion of coronary heart
      disease. All 59 previously published cases (44 found at coronary angiography, 15
      at necropsy) and our own three cases were not associated with other
      cardiovascular anomalies. A pathophysiological significance of this anomaly alone
      with regard to inducing myocardial ischemia can almost be excluded. The knowledge
      of this anomaly however is important to avoid errors in diagnosis and to evaluate
      the exact degree of severity of coronary heart disease.

PMID- 8147057
TI  - [Growth stimulating properties of angiotensin II on the heart: consequences for
      therapy of heart failure].
AB  - Several well controlled multicenter trials demonstrated the great value of ACE
      inhibitors in the treatment of heart failure. Interestingly, the mechanisms by
      which ACE-inhibitors improve survival of patients with heart failure are ony
      poorly understood. Interesting new aspects regarding the role of the renin
      angiotensin system in the pathophysiology of heart failure emerged from modern
      methods of molecular biology. For example, several alleles of the angiotensin
      converting enzyme or angiotensinogen genes were related to hypertension and
      myocardial infarction in both clinical and experimental studies. Furthermore,
      local renin angiotensin systems have been demonstrated in various cardiovascular
      tissues. These tissue renin angiotensin systems are independently regulated and
      may be activated in heart failure or cardiac hypertrophy. Finally, it has been
      shown that inhibition of angiotensin converting enzyme affects also the
      metabolism of bradykinin and aldosterone which may contribute to the overall
      pharmacodynamic profile of ACE-inhibitors in heart failure.

PMID- 8147058
TI  - [Diagnostic and therapeutic problems in hypertensive heart disease].
AB  - The main important diagnostic and therapeutic problems in hypertensive heart
      disease refer to the further improvement in the diagnostic procedures in
      hypertensive hypertrophy; moreover, structural changes of the hypertrophied
      myocardium have to be analyzed. Quantitative findings concerning the coronary
      circulation as well as the global and regional myocardial perfusion are
      desirable. The incidence of ventricular arrhythmias has to be clarified. Further
      diagnostic studies are needed with regard to the rheological changes as well to
      the mechanisms for silent and manifest myocardial ischemia. From the therapeutic
      point of view future studies are desirable concerning the regression of
      myocardial and vascular hypertrophy, with the aim to find out the optimal therapy
      for treating both high blood pressure and the hypertension induced structural
      myocardial and vascular alterations.

PMID- 8147059
TI  - [Dilated cardiomyopathy--a chronic myocarditis? New aspects on diagnosis and
      therapy].
AB  - Clinical and experimental data suggest that autoimmunological mechanisms may play
      an important role in the pathogenesis of postmyocarditic cardiomyopathy. This may
      be due to the viral infection itself, or may be induced by persistence of the
      virus. Apart from the clinical signs of myocarditis, which are usually not
      specific, the diagnosis of acute myocarditis should be enabled by the
      histological examination of endomyocardial biopsies. In accordance with the
      Dallas criteria the histological diagnosis of acute myocarditis is defined by the
      presence of inflammatory cells in the myocardium associated with myocyte necrosis
      and degeneration of adjacent myocytes. This morphology, however, is only seen
      within the first 7 to 10 days of the acute stage of the disease. Later, most
      cases of clinically suspected acute myocarditis are histopathologically
      consistent with the diagnosis of "borderline myocarditis". Although
      endomyocardial biopsies have markedly improved diagnostic possibilities, the
      diagnosis of myocarditis by light microscopy has its limitations. Mainly the
      differentiation of infiltrating mononuclear cells from interstitial fibroblasts
      or pericytes is visually difficult. New immunohistochemical methods were
      therefore introduced to improve the specificity and sensitivity of the diagnosis.
      Using monoclonal antibodies against cell surface markers from lymphocytes (CD3,
      CD4, CD8) the identification, characterization and quantification of lymphocytic
      infiltrates in the myocardium is improved very significantly. Furthermore, the
      use of monoclonal antibodies against MHC-class-I and class-II-antigens provides
      further information about the immunological status of the myocardium. In
      conclusion, the use of these new immunohistological methods offers the
      possibility of establishing immunological criteria in addition to histological
      parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147060
TI  - [Is hyperlipidemia a factor in the progression of renal failure?].
AB  - Many experimental results support the hypothesis that increased plasma lipid
      concentrations may have a deleterious effect on the course of chronic renal
      diseases. Until now a clear causal relationship has not been proved. Because
      reliable results of prospective controlled trials are not available that would
      demonstrate a beneficial effect of lipid-lowering interventions on the course of
      chronic renal diseases, it is not possible at this time to provide a general
      recommendation for a lipid-lowering drug therapy. Nevertheless, I would support
      the prescription of HMG CoA reductase inhibitors for patients with extremely
      increased total cholesterol and LDL cholesterol concentrations despite the
      restricted data of already existing experimental and clinical studies. It should
      be stressed that every patient with glomerular disease and concomitant
      hyperlipidemia constrains us to weigh advantages and side-effects of a lipid
      lowering regimen. We have to wait for the results of prospective and controlled
      multicenter studies to give a final recommendation for therapeutic consequences
      in patients with chronic renal disease and hyperlipidemia.

PMID- 8147061
TI  - [Therapy of diabetic nephropathy].
AB  - New pathophysiological insights in the last few years on the development of
      diabetic nephropathy have led to a change in therapeutic measures. The emphasis
      is put on preventive considerations for the insulin-dependent diabetic patient.
      Strict control of glycemia and the early use of an angiotensin-conversion
      inhibitor are of importance. Therapy of the manifest diabetic nephropathy is
      based on strict metabolic control combined with reduced protein intake.
      Furthermore, an often co-existing hypertension needs to be treated. Normotensive
      blood pressure should be obtained. ACE-inhibitors and Ca-antagonists have been
      proven to be very effective, although there seem to exist differences in the type
      of Ca-antagonists regarding effectiveness on albuminuria. The combination of ACE
      inhibitors and Ca-antagonists seems to have an additional beneficial impact on
      albuminuria. A significant decrease in the loss of glomerular function and a
      decrease in albuminuria can be obtained by consistent consideration of these
      therapeutic strategies.

PMID- 8147062
TI  - [Dyslipoproteinemia: its importance in nephrology].
AB  - Dyslipidemia is a common feature of renal failure. It is primarily caused by
      delayed catabolism of lipoprotein particles. This is due to decreased activity of
      the key enzymes of delipidation of lipoprotein particles (LPL, HTGL) and of HDL
      remodeling (LCAT). In epidemiological studies no correlation has been found in
      dialysis patients between total lipids and atherosclerotic endpoints and a modest
      relation, at best, between more sophisticated apolipoprotein indices and vascular
      disease. Such lack of correlations are presumably explained by malnutrition as a
      confounding factor. Fascinating new observations in animal studies document that
      in various models of renal damage, development of glomerulosclerosis is
      accelerated by hyperlipoproteinemia, either endogenous hyperlipoproteinemia or
      hyperlipoproteinemia induced by feeding of fat. Conversely, correction of
      hyperlipoproteinemia mitigates development of glomerulosclerosis. Currently there
      is no firm evidence that the same is true in humans.

PMID- 8147063
TI  - [Rational therapy of heart failure].
AB  - To stop or reverse progression of congestive heart failure is so far an unreached
      therapeutic goal. Several prospective studies have now clearly shown that
      treatment with angiotensin-converting enzyme (ACE) inhibitors resulted in a clear
      reduction of cardiovascular and total mortality in patients with congestive heart
      failure. As a consequence, ACE-inhibitors are now standard therapy for congestive
      heart failure in addition to diuretics and glycosides. Of pathophysiologic
      importance is that ACE-inhibitors are potent vasodilators and counteract the
      neuroendocrine stimulation of the sympathetic nervous system and the renin
      angiotensin-aldosterone system which both contribute to the detrimental outcome
      in congestive heart failure. New results of the prevention trial of the SOLVD
      Study showed that in patients with reduced ejection fraction the development of
      congestive heart failure could be attenuated or even stopped. The questions
      remain of what is the optimal dose, when should treatment with ACE-inhibitors be
      started, and how long should it be maintained. Thus, in patients with reduced
      ejection fraction after myocardial infarction ACE-inhibitors are today a
      cornerstone for preventing progressive congestive heart failure and improving
      cardiovascular prognosis. Whether beta-blockers offer additional benefit in
      subgroups of patients with congestive heart failure remains to be determined in
      future trials.

PMID- 8147064
TI  - [Single or multiple balloon inflations in coronary angioplasty? Acute results and
      long-term angiography results of a prospective, randomized study of 300
      patients].
AB  - 325 coronary lesions in 300 consecutive patients (257 male, 43 female, 52 +/- 8
      years) undergoing either single-vessel (n = 275) or double-vessel PTCA in two
      independent procedures (n = 25) were prospectively randomized to either one
      (group A, n = 167) or three (group B, n = 168) balloon inflations. By clinical
      and angiographic criteria, PTCA was successful in 295/325 lesions (90.8%) with no
      significant difference for group A (88.6%) and B (93.0%). Clinical follow-up was
      achieved in 92% of patients and angiographic follow-up was obtained in 261/295
      (88.5%) successfully dilated lesions (A: 87.8%; B: 89.1%). Angiographic
      appearance of the dilated lesion (in % diameter stenosis) prior to PTCA, directly
      following PTCA and at follow-up was comparable for both groups: gr. A: 71 +/-
      11%, 32 +/- 10%, and 40 +/- 21%; gr. B: 70 +/- 11%, 30 +/- 10%, and 40 +/- 20%
      resp. Restenosis rate was similar with 26.9% in group A and 29.8% in group B. The
      randomization had to be abandoned in 144/325 cases (44.3%) due to medical
      reasons. Results of only those lesions where it was possible to follow the
      initial randomization demonstrated a different pattern. Success rate was slightly
      higher in those with 3 inflations (gr. B1, n = 111) with 93.0% as compared to
      lesions with only one inflation (gr. A1, n = 70) with 88.6% success (p = ns).
      Subsequently, the initial angiographic result was slightly better for B1 with a
      reduction in diameter stenosis from 69 +/- 11% to 29 +/- 10% compared to A1 (71
      +/- 11% and 32 +/- 10% resp.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147065
TI  - [Antibiotic therapy of infectious endocarditis (when, with what drug, how long?].
AB  - The aim of antibiotic therapy in bacterial endocarditis is to sterilize infected
      cardiac structures and vegetations. Pathogenic organisms are present in great
      numbers within vegetations and abscess-formations. They exist in a state of
      reduced metabolic activity so that they are able to tolerate even therapeutic
      levels of bactericidal antibiotic concentrations. Because vegetations are
      normally devoid of blood vessels, impregnation with antibiotic agents is poor.
      Effective therapy is greatly improved by identification of the pathogenic
      organism involved. With very few exceptions isolation is possible prior to
      initiation of antibiotic therapy. In acute cases with signs of septicemia,
      however, therapy cannot await results of bacterial testing. In these patients
      selection of antibiotic agents is based on associated evidence such as the
      presence of a prosthetic heart valve or intravenous drug addiction. Once the
      pathogen has been identified antibacterial therapy should be tailored according
      to the test results. Bactericidal antibiotics should always be preferred over
      bacteriostatic agents; in many cases adequate bactericidal levels can only be
      achieved by combining various agents, such as ampicillin and gentamycin for
      treatment of enterococcal endocarditis. Dosing intervals must take into account
      the resulting trough levels, which should always exceed the minimal inhibitory
      concentrations for a specific bacterial strain. In cases with inadequate control
      of infection, congestive heart failure resulting from valve dysfunction, and
      abscess formation, surgery as the only means of eradicating the infection and
      restoring cardiac performance should not be delayed.

PMID- 8147066
TI  - [Does rotablation of complex coronary artery stenosis lower the risk of
      subsequent PTCA?].
AB  - To answer the question of whether pretreatment of complex coronary artery lesions
      via rotablation reduces the risk of subsequent PTCA, we compared the results of
      PTCA of 250 patients with Typ B- and C-lesions treated between April 1 and
      November 11 1991 (Group A) with a group of 437 patients treated between January 1
      and May 1 1992 (Group B), for whom not only PTCA but also rotablation was
      available. Rotablation was successful in 102 of 119 procedures (85.7%), the rate
      of major complications was 1.8%. The primary success rate for treatment of all
      complex lesions was higher in group B (87.3%) in which 22.2% of the lesions were
      treated with the rotablator than in group A (83.1%). Dissection rate was similar
      in both groups (18.5% in group A, 17.5% in group B). In group B patients,
      however, dissections could be controlled more frequently by the use of a
      reperfusion catheter (21% vs 8.3% in group A). Serious complications caused by a
      dissection were not so often observed. In group B patients the rate of major
      complications due to dissection was lower (2.5% vs 4.4% in group A). In summary,
      pretreatment of complex coronary artery lesions via rotablation seems to increase
      the success rate of the following PTCA and to reduce its risks.

PMID- 8147067
TI  - [Changes in infectious endocarditis--analysis of a disease picture in the last
      decade].
AB  - The following retrospective study analyzes 51 patients aged 45.8 +/- 11 years
      with infective endocarditis diagnosed from January 1, 1980-December 31, 1989. The
      aortic valve was mainly affected (59%). 92% of patients showed predisposing
      factors or a directly related incident. Positive blood cultures were found in 63%
      of patients. The dominating bacterium was streptococcus viridans (31%) with
      decreasing tendency compared to the previous decade, followed by staphylococcus
      aureus (22%) with significantly increasing tendency. Clinical and laboratory
      findings were not different from those of the previous decade. Main complications
      in the early period of disease turned out to be acute heart failure (69%) and
      arterial embolism (41%) which was dependent on the severity of disease. Mortality
      within the initial 6 months was significantly lower than in the previous decade
      (16% vs 31%). Patients undergoing heart-valve replacement within the first 6
      months of disease (59%) had a mortality rate of 10%, which was significantly
      smaller than the 24% mortality rate of patients not being operated during the
      same period. Furthermore, patients with staphylococcus aureus endocarditis
      demonstrated a markedly worse early prognosis (6 month survival rate 28.6 +/-
      17.2% vs 80.0 +/- 6.1% in patients with infective endocarditis other than
      staphylococcus aureus-related). Late mortality was not different in the above
      mentioned subgroups with a 5-year survival of more than 80%. However, surgically
      treated patients significantly improved their functional class in the follow-up
      period over medically treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147068
TI  - [Cardiopulmonary stress in hyperthyroidism].
AB  - Spiroergometry might be applicable to detect alterations of cardiopulmonary
      functions related to hyperthyroidism. Thus, cardiac and respiratory changes as
      well as work capacity in hyperthroid female patients were to be assessed with the
      help of the Cardiopulmonal Exercise Test System. Twelve female hyperthyroid
      patients with Graves' disease of whom all were controlled in euthyroidism, were
      examined. Eighteen euthyroid female patients in whom intracardiac catheter
      examination ruled out cardiopulmonary disease served as controls. The anaerobic
      threshold was determined by means of the V-slope method. An echocardiography was
      performed in all patients. Ergometry was performed in a semisupine position using
      a continuous ramp protocol of 20 watt/min. A markedly reduced work capacity, and
      a high heart rate in rest and exercise were found. In the ratio heart rate/oxygen
      uptake a lower rise (p = 0.001) due to a decreased growth in the heart rate was
      noticed. Regarding the pulmonary system a decreased tidal volume in
      hyperthyroidism (p = 0.021), and a higher breathing frequency (p = 0.003) were
      recognized, as well as an impaired oxygen consumption, in comparison with the
      euthyroid state. Also, echocardiographically an increased cardiac index (p =
      0.008) and a markedly reduced stroke volume (p = 0.005) in comparison to the
      control group were observed. Heart rate, work capacity, oxygen uptake, and the
      ratio heart rate to oxygen uptake were normalized in euthyroidism. With the help
      of the CPX-System noninvasive measure of marked cardiopulmonary changes in
      hyperthyroidism are possible, especially the lower growth of the heart rate in
      exercise, which might be the limiting factor of work capacity.

PMID- 8147069
TI  - [Reproducibility of symptom-limited oxygen consumption and anaerobic threshold
      within the scope of spiroergometric studies in patients with heart failure].
AB  - A prerequisite for the clinical utility of cardiopulmonary exercise testing is
      high reproducibility of gas-exchange characteristics. Therefore, we studied
      reproducibility of peak oxygen uptake and anaerobic threshold during bicycle
      exercise stress testing in 34 patients with congestive heart failure in NYHA
      classes II and III. Additionally, we analyzed interobserver variability with
      regard to anaerobic threshold measured with the V-slope method. Correlations of
      results between two exercise stress tests were high concerning peak oxygen uptake
      and anaerobic threshold (r = 0.871 and r = 0.917, respectively). For both
      measures, however, 90% percentile of the relative difference between tests was
      25% and 22%, respectively. Correlation between two observers with regard to the
      anaerobic threshold was high (r = 0.985). We conclude that reproducible
      determination of peak oxygen uptake and anaerobic threshold is possible in heart
      failure patients. In individual subjects, however, considerable variation of
      results may occur during serial exercise testing. Interobserver variability with
      regard to anaerobic threshold is low.

PMID- 8147070
TI  - [Effect of nisoldipine and diltiazem on systolic and diastolic function of the
      left ventricle in patients with coronary heart disease].
AB  - OBJECTIVES AND BACKGROUND: Calcium channel blockers have a negative inotropic
      effect and protract the relaxation of the normal myocardium. These effects may
      vary in patients with coronary artery disease (CAD) and with the different kinds
      of calcium antagonists. In the present study we therefore compared the
      hemodynamic effects of intravenously given equihypotensive dosages of diltiazem
      (D) and nisoldipine (N) in patients with CAD. METHODS AND RESULTS: Each group
      contained 10 patients. After administration of a bolus of 300 micrograms/kg (D)
      and 5 micrograms/kg (N) respectively and following continuous infusion of 5.4
      micrograms/kg/min (D) and 0.2 micrograms/kg/min (N) respectively, the mean
      arterial pressure was reduced by 15.5 +/- 6.0 (D) and 16.6 +/- 4.1 (N) mm Hg.
      Atrial pacing was performed in all patients to avoid reflectory heart rate
      effects. The pulmonary artery pressure decreased slightly with both drugs,
      whereas the cardiac index increased only with the use of N from 3.44 l/min x m2
      to 3.93 l/min x m2. A significant change in the maximal rate of rise of left
      ventricular pressure (dP/dt max) as an index for inotropy was not detected for N
      or for D. The parameters of the diastolic function (the time constant of
      ventricular relaxation (tau) and the maximum rate of left ventricular isovolumic
      pressure decline (dP/dt min)) also did not indicate unequivocal drug effects.
      Doppler echocardiography of the mitral valve flow was performed simultaneously
      with invasive pressure measurements. The flow propagation derived from the color
      M-mode correlated significantly with tau and was slightly improved by D.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8147071
TI  - [Comparison of the negative inotropic properties of nifedipine and nisoldipine
      using isovolumetric contractile parameters of the rat in vivo].
AB  - The vasoselectivity of new dihydropyridine calcium antagonists is much higher as
      compared to their prototype substance nifedipine. To investigate whether an
      equihypotensive dose of a new dihydropyridine has less negative inotropic
      properties in an intact circulation, nifedipine (NIF) and nisoldipine (NIS) were
      infused intravenously in an open-chest, anaesthetized rat model. The maximal
      isovolumic left ventricular pressure (LVPiso) and the maximal isovolumic rate of
      change of LV-pressure (dp/dtmaxiso) were determined to achieve load independent
      parameters of LV contractility. To evaluate the effect of the infused volume, the
      stability of the preparation and the hemodynamic effects of the drug-solvent, two
      groups with either infusion of isotonic NaCl-solution or 20% ethanol served as
      controls. NIF and NIS were infused in three equihypotensive doses within 7 min
      (NIF 250, 500, 1000 micrograms/kg; NIS 12.5, 25, 50 micrograms/kg). The decrease
      of the peripheral resistance of these doses was 74 +/- 6, 67 +/- 6, and 58 +/- 7%
      for NIF, and 78 +/- 7, 65 +/- 8, and 56 +/- 7% for NIS (p < 0.001 for all
      groups). In the control groups the afterload remained unchanged. NIF-infusion
      resulted in a dose-dependent decrease of LVPiso at the end of the infusion period
      (in percent of controls: NIF250 88 +/- 3%, p < 0.001; NIF500 74 +/- 3%, p <
      0.001) as well as 15 min after the end of the infusion. In the same way
      dp/dtmaxiso decreased significantly after NIF at the end of infusion (NIF 250 82
      +/- 6%, p < 0.001; NIF500 61 +/- 8%, p < 0.001) and 15 min after the end of the
      infusion. After NIS-infusion the contractility parameters decreased slightly
      after the higher dosage (25 micrograms/kg) at the end of the infusion period only
      (LVPiso 96 +/- 3%, p < 0.01; dp/dtmaxiso 93 +/- 5%, p < 0.01). There was no
      depressive effect on the isovolumic contractility parameters at the end of
      infusion of the lower dosage and 15 min after the drug-infusion of all dosages of
      NIS. Therefore, nisoldipine, as an example of a new dihydropyridine, has
      significantly less negative inotropic properties over a wide range of doses as
      compared to nifedipine in equihypotensive doses.

PMID- 8147072
TI  - [Report on the structure and capacity of heart catheterization laboratories in
      Germany. Results of a 1992 survey of the Commission of Clinical Cardiology of the
      German Society of Cardiovascular Research with the collaboration of the German
      Society of Pediatric Cardiology].

PMID- 8147073
TI  - [Risk factors in hyperlipidemic patients with coronary heart disease one year
      after PTCA].
AB  - The reduction of modifiable risk factors in hyperlipidemic patients with coronary
      heart disease (CHD) receiving standard medical care in Germany has not been
      evaluated before. We identified all patients < 65 yrs of age with marked
      hyperlipidemia (Cholesterol (Chol) > 250 mg/dl, HDL < 20% Chol) among all
      patients who underwent PTCA during defined periods 1991/92 in the Cardiology
      department of the Heinrich-Heine-University. The study patients (n = 93, age 54
      +/- 8 yrs, 75 men, 18 women) were evaluated 13 +/- 2 months after PTCA for
      modification of their risk factors, treatments, knowledge, medications and
      dietary habits with a structured questionnaire and a 5-day dietary protocol. At
      follow-up Chol and LDL were significantly reduced from 299 +/- 47 to 253 +/- 43,
      and from 228 +/- 47 to 189 +/- 42 mg/dl, respectively (p < 0.001). 10% of
      patients had an LDL < 135 mg/dl. In contrast, HDL (43 +/- 9 mg/dl) and
      triglycerides (242 +/- 138 mg/dl), the percentage of smokers (40%), of overweight
      patients (38%) and of patients with elevated blood pressure (43%) remained
      unchanged. During the observation period the number of contacts with physicians
      was high (12 (1-40)). 32% of patients participated in dietary counselling by a
      dietician and 42% in an in-patient rehabilitation programme. In 2/3 of patients
      the knowledge related to hyperlipidemia and a lipid-lowering diet was good.
      However, according to the dietary protocols the fat intake was high (37 +/- 7% of
      total calories). Lipid lowering drugs had been prescribed in 68% of patients,
      predominantly as monotherapy and in low dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147074
TI  - [Nutrition as prevention of illness in the elderly].
AB  - Nutrition-related diseases are the primary health problem, not only of the aged,
      but also of the whole population in industrialized countries. While the health
      risks of overnutrition are well considered in prevention and medical care, the
      consequences of malnutrition are often disregarded. Nutritional counseling, early
      diagnosis, and therapy of nutritional risk factors are able to improve quality of
      life and prognosis of the aged and should be performed more intensively in
      medical care.

PMID- 8147075
TI  - [How can preparation for old age become a tool for prevention?].
AB  - Preparation for old age is defined as the sum of all efforts at any point in the
      life-course for better coping with old age. Eight theoretical orientations are
      sketched from which conclusions for the preparation for old age may be deduced.
      Nine points of critique are formulated (ethical objections, compensatory
      function, provision for work, retarded beginning, partially false content, needy
      people are not reached, neglect of the information diffusion processes and of the
      interindividual differences, low results). Four postulates concerning a
      responsible preparation for old age conclude the article (professionalization,
      extended time perspective, diversification, continuous amelioration by
      evaluation).

PMID- 8147076
TI  - [Exercise as prevention of illness in the elderly].
AB  - The physiologic changes of the different organs in the elderly result in a
      diminishing efficiency of the organism and its capability of adapting to new and
      unusual conditions. Accordingly, physical exercise has to be seen and assessed as
      prevention of illness in old age. In terms of prevention exercise training is
      taking the first place within the five different types of physical activities.
      The other types (coordination, flexibility, strength, rapidity) have to be
      handled with special conditions, whose importance must be assessed individually.
      The importance of exercise, physical activities, and sports is increasing
      especially in preventing coronary artery disease. Metabolic diseases,
      hypertension, impairment of cerebral functions and also diseases of the
      musculoskeletal system are improving under suitable physical training. General
      training exercise training slows down the loss of cardiopulmonal efficiency due
      to progredient aging. Risks and benefits of physical training have to be
      deliberated very carefully in considering the state of health of the elderly.

PMID- 8147077
TI  - [Primary and secondary pharmacologic prevention in geriatrics].
AB  - A review is given on general aspects and specific indications of preventive drug
      treatment. Particularly in the elderly, drug prescription for preventive reasons
      has to be considered according to risk/benefit aspects. Quality of life is a
      major concern for patients on long-term treatment. However, relevant
      investigations have been few, and clear therapeutic guidelines are still lacking,
      especially for the old-old. Most important areas of preventive medication are
      cardio- and cerebrovascular diseases. Further topics of prevention include the
      prophylaxis of thromboembolic complications, osteoporosis, postmenopause, and
      vaccinations.

PMID- 8147078
TI  - [Is prevention of dementia possible?].
AB  - Dementia is a clinical syndrome with many causes. Dementia of the Alzheimer type
      and vascular dementia account alone or in combination for the vast majority of
      the dementia in the elderly population. Primary prevention depends on the
      knowledge of etiopathogenetic mechanisms and the possibility to change
      contributing factors. In the case of dementia of the Alzheimer type (DAT)
      contributing factors (risk factors) are emerging. However, they are not easily
      altered. The protective effect of certain micronutrients, such as antioxidants,
      remains speculative. The well-established cardiovascular risk factors such as
      hypertension, diabetes, and overweight are effective in the etiopathogenesis of
      vascular dementia. Their treatment by diet and drugs is therefore indicated. The
      protective role of antioxidants is better established in vascular dementia.
      Antioxidant micronutrients could be an important part of the primary preventive
      strategy. Whether mental training is effective in primary prevention or not
      remains controversial. Better training allows the individuals to optimize their
      resources. In secondary prevention, mental training was shown to be effective in
      mild dementia (MMS > or = 23), maintaining or even improving function (vascular
      dementia) and maintaining function for a given time in DAT. In the population
      with advanced age, mixed forms of dementia become increasingly common. Hence,
      patients with mild dementia should receive mental training as well as a vigorous
      treatment of established risk factors.

PMID- 8147079
TI  - [Secondary prevention from the viewpoint of the geriatric specialist].
AB  - Secondary prevention is of importance when the patient is already suffering from
      a serious disease, e.g., from arterial obstruction causing a stroke or an
      amputation, from a hip fracture or other diseases that might threaten his
      independence. Secondary prevention covers a wide field of topics. First of all,
      the patient must recover from his acute disease. It is important to avoid
      complications which are not specific for the disease, but are typical for a
      bedridden old person (decubital ulcer, dehydration and others). Prevention also
      means to avoid recurrence of the same disease as well as complications that
      frequently occur during the clinical course and may influence the outcome
      (spasticity in stroke patients, muscular calcification following hip
      replacement). Frequently, old persons do not completely recover following serious
      disease, they are limited in their daily activities and their capability to leave
      home. Secondary prevention tries to fight isolation; the patient should live a
      meaningful life.

PMID- 8147080
TI  - [Prevention in residential and nursing homes].
AB  - "Health" in the elderly describes an instable balance that exists between
      physical, psychological, and social factors as they pertain to the individual.
      The disruption of this balance can render the patient incapable of taking care of
      himself, thus requiring comprehensive care either at home or in an institution.
      Even the circumstance under which a transfer to an institution is made can have a
      negative effect on the subjects health; a careful analysis should be made of
      these factors before a decision to transfer is made. The following factors are
      critical in preventing or limiting the negative impact of either home or
      institutional care: architectural structuring of the environment organization of
      patient care type of medical care required type of physical therapy required It
      is a primary importance that the parties involved (patient and immediate family)
      be allowed to make and/or influence the decision on care and that they retain a
      feeling of personal responsibility for what happens. When a patient is
      institutionalized, he should be given the chance to continue his individual
      lifestyle whenever possible; his private sphere should be maintained.
      Disturbances that are caused by inappropriate changes in these structural factors
      should not be considered symptoms requiring psychopharmacological therapy.

PMID- 8147081
TI  - [Illness as a problem solving approach. Case presentation for comprehending
      psychosomatic illness in the elderly].
AB  - From a psychosomatical view, one's present situation in life, previous
      experiences of conflict and uncoped with losses play, especially in old age, an
      important role in the development of, the course of, and the coping with the
      underlying physical disease. It is shown in the example of a 68-year-old patient
      with bronchial asthma that sickness in old age can be understood as an effort
      (certainly not an optimal one) to solve the psychosocial conflicts, and as an
      adjustment process to altered living conditions.

PMID- 8147082
TI  - [A gerontopsychological pilot study on the sleep of the very elderly--initial
      experiences with the Nurnberg Gerontopsychologic Inventory].
AB  - In an ongoing study of sleep in aged seniors the relationship between
      physiological, pathophysiological changes of sleep parameters and cognitive
      function was studied. It will be argued that the Nuremberg gerontopsychological
      inventory is superior to commonly used psychometric test-batteries to assess
      cognitive function in the aged. Preliminary results on the application of the
      Nuremberg gerontopsychological inventory will be presented, which were achieved
      in 10, non-demented, independently living subjects aged 80 to 85 years. The
      relationship between subjective complaints on aging, everyday activities and
      psychometric assessed performance was analyzed in detail.

PMID- 8147083
TI  - [Activating ergotherapy--a method for increasing cognitive performance in
      geriatric patients].
AB  - A study was performed in two groups of multimorbid longterm geriatric inpatients
      (n = 22 in each group). This compared the effects of re-activating occupational
      therapy (= study-group) on cognitive functions, subjective well-being,
      affectivity and social integration. The control group was monitored with a normal
      program of functional rehabilitation. The assessment of psychometric variables
      after 12 weeks and after 24 weeks of treatment revealed a significant (p < 0.01)
      improvement in cognitive functioning and subjective well-being in the study
      group. These results demonstrate the therapeutic benefit of re-activating
      occupational therapy in the treatment of cognitive impairment of geriatric
      patients, which is often aggravated by hospitalization.

PMID- 8147084
TI  - [The epidemiology of stroke].
AB  - A special significance is attached to stroke in geriatrics, because, with its
      complex clinical manifestation and the far-reaching consequences for the patient,
      the social surroundings, and for society, it is the diagnosis which is most in
      the foreground in both acute geriatrics and in rehabilitative geriatrics and
      care. The work presented gives an overview of the essential epidemiological
      aspects of stroke: mortality, lethality, incidence, prevalence, risk factors and
      predictors. Furthermore, the socio-epidemiological aspects are considered in the
      light of psychiatric and social risk factors, as there is a considerable lack of
      research in this area. And not least, the care aspect and the economical
      relevance of the care of stroke patients, as a logical consequence, are also
      dealt with.

PMID- 8147085
TI  - [Residential gerontopsychiatry or who helps homes in management of psychiatric
      elderly patients? A study of all old age and nursing homes of the Gutersloh
      district 1991].
AB  - In 1991, there existed 20 homes and nursing homes for the elderly in the district
      of Gutersloh (Nordrhein-Westfalen, Federal Republic of Germany) with a total of
      1518 beds. 56,000 persons aged 60 years and more rsp. 41,000 persons aged 65
      years and more are living in this area. This means 2.7 beds per 100 persons aged
      60 years and more are provided, or 3.7 beds per 100 persons aged 65 years and
      more. 22.5% of the home residents are in need of care, grade II (care is
      necessary for some activities of daily living), 55.6% are in need of care, grade
      III (care is necessary in most or all activities of daily living). Only three of
      the homes have a special department or ward for residents with high grades of
      need of care; in all the other homes residents with high grades of need of care
      are supported together with residents with lower grades of need of care. One home
      has a special psychogeriatric department with two wards, another one a single
      psychogeriatric ward. The leading staff members of the homes assessed that 831
      out of 1861 residents in the whole year 1991 were mentally disordered, i.e., a
      rate of 44.65% in which is similar to the results of comparable studies. 75% of
      the admissions of mentally disordered persons are arranged by family members or
      relatives. Only 7% come directly from the psychogeriatric department of the
      responsible psychiatric clinic in the area (Westfalische Klinik fur
      Psychiatrie).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147086
TI  - [Recommendation for new classification of manual lymph drainage therapy].

PMID- 8147087
TI  - [Craniocerebral trauma caused by sports. Pathogenic mechanism, clinical aspects
      and physical therapy with special reference to manual lymph drainage].
AB  - On top of one comprehensive English accident statistics of head injuries in
      sports there is riding, followed by rugby and football. In Germany there is not
      very little of head and brain damage due to football as wide spread sports,
      followed by riding, athletics and gymnastics, whereas in boxing recurring head
      injuries of dosage underlaying concussion of the brain do play a part even in
      spite of wearing boxing caps. Anyway, damage of the brain will always be the most
      heavy complication. Besides uncomplicated wounds of the soft parts such as wounds
      of the scalp or contusion of the face the closed skull and brain damage will be
      the most generally form of head injury in sports, followed by fractures of the
      skull with contusion of the brain and intracranial hemorrhage. In the treatment
      of the post-concussion and post-contusion syndrome manual lymph drainage will
      achieve more importance by its anti-edematous and therefore depressant and also
      sedative effects.

PMID- 8147088
TI  - [Edema after vascular surgery interventions and its therapy].
AB  - The incidence of lymphodemas after vascular surgical reconstructions is
      underestimated. In stage III and IV of PAOD 80% of our patients are suffering
      from lymphodemas, in stage II about 30%. In stage III and IV a postreconstructive
      edema occurs more often, in stage II the incidence of both, secondary lymphedema
      and postreconstructive edema is similar. A complex physical therapy (CPT) after a
      successful surgical reconstruction decreases the swelling of the legs by special
      lymphatic massage and the patients are earlier rehabilitated. The lymphatic
      massage should be applied only in patients with high degree lymphedematous legs.
      Because of the improvement of microcirculation a benefit for the healing of
      trophic lesions could be considered.

PMID- 8147089
TI  - [Social medicine aspects in lymphatic and oncologic diseases].
AB  - Lymph flux disturbance lead to social changes in the life of the patient. In
      crafts and administration there are numerous occupations which interfere with the
      pathophysiological conditions of the lymphedema patient. This is being discussed
      in patients with breast cancer who underwent axillary dissection. Matters of
      legislation in retirement and handicap have to be reflected. In addition, current
      problems in the prescription of physical theory in lymphedema patient are
      reviewed.

PMID- 8147090
TI  - [Psychological management of breast cancer patients in a therapy group. II.
      Practical experience].
AB  - In 1991 group meetings have been established in the REHA-Klinik Damp to improve
      the coping ability of breast cancer patients. Information about the medical
      treatment was given to reduce uncertainty and anxiety. The psychical and social
      consequences, for instance, changes in self-consciousness and family life were
      discussed in their positive and negative aspects. Talking about their personal
      concerns and getting support by other women was a new experience for those who
      had not been in a self-help group before. Many breast cancer patients took the
      opportunity to reflect their needs and wishes to increase contentment in their
      lives. The following article describes the most important subjects being
      discussed in the group meetings and their significance for the coping ability of
      women with breast carcinoma.

PMID- 8147091
TI  - Safety, immunogenicity and limited efficacy study of a recombinant Plasmodium
      falciparum circumsporozoite vaccine in Thai soldiers.
AB  - Thai soldiers were vaccinated with a recombinant protein derived from the central
      repeat region of the circumsporozoite (CS) protein of Plasmodium falciparum
      conjugated to Toxin A (detoxified) of Pseudomonas aeruginosa (R32Tox-A) to
      evaluate its safety, immunogenicity and efficacy. In a randomized, double-blind
      manner, 199 volunteers received either R32Tox-A or a control vaccine at 0, 8 and
      16 weeks. Immunization was performed in a malaria non-transmission area, after
      completion of which volunteers were deployed to an endemic border area and
      monitored closely to allow early detection and treatment of infection. The
      vaccine was found to be safe and to elicit antibody responses in all vaccinees.
      Peak CS antibody (IgG) concentrations in malaria-experienced vaccinees exceeded
      those in malaria-naive vaccinees (mean 40.6 versus 16.1 micrograms ml-1; p =
      0.005) as well as those induced by previous CS protein-derived vaccines and
      observed in association with natural infections. A log-rank comparison of time to
      falciparum malaria revealed no differences between vaccinated and non-vaccinated
      subjects. Secondary analyses revealed that CS antibody levels were lower in
      vaccinee malaria cases than in non-cases, 3 and 5 months after the third dose of
      vaccine (p = 0.06 and p = 0.014, respectively). Because antibody levels had
      fallen substantially before peak malaria transmission occurred, the question of
      whether high levels of CS antibody are protective remains to be resolved.

PMID- 8147092
TI  - Epidemiological model of diarrhoeal diseases and its application in prevention
      and control.
AB  - In this paper, a prototype epidemiological model of acute bacterial and viral
      diarrhoeal diseases occurring in young children is formulated. The model is able
      to mimic the observed epidemiological patterns of infantile diarrhoeal diseases
      associated mainly with enterotoxigenic Escherichia coli or with rotavirus. The
      proposed mathematical model predicts a plausible pattern of the serological
      profile of an enteric infection. According to computer simulation experiments
      (CSE) with this model, it is not necessary to develop an enteric vaccine
      conferring total and long-lasting immunity in order to achieve protection from
      diarrhoeal diseases in young children. Given a protective efficacy and a finite
      duration of vaccine-induced protection, the optimal immunization policy must be
      sought. Oral rehydration therapy (ORT) intervention has a clear effect in
      diminishing the number of individuals dying from diarrhoeal illness. The CSE also
      predict an apparent reduction in age-prevalence of diarrhoeal diseases by use of
      ORT.

PMID- 8147093
TI  - Measles antibody: comparison of long-term vaccination titres, early vaccination
      titres and naturally acquired immunity to and booster effects on the measles
      virus.
AB  - A two-dose vaccination programme, using a combined measles, mumps and rubella
      vaccine (MMR) and administration at the ages of 18 months and 12 years, was
      introduced into Sweden in 1982. Since the combined MMR vaccine was introduced, a
      yearly evaluation of the immunity patterns and seroconversion rates in 12-year
      old children has been carried out. This study includes three study groups. All
      groups consisted of pre- and postvaccination samples from 12-year-old children
      taken in connection with the MMR immunization. There were 332 paired samples from
      children who 8-10 years previously had received live measles vaccine.
      Prevaccination sera from these children represent late postvaccination titres.
      The postvaccination sera of 49 children seronegative to measles before
      vaccination, obtained 2 months after vaccination, represent early postvaccination
      immunity. Ninety-five children who had not been vaccinated earlier and who were
      seropositive to measles represent naturally acquired immunity. All samples were
      studied by an enzyme-linked immunosorbent assay (ELISA). Sera from children with
      late postvaccination immunity had significantly lower titres than children in
      group 2, who represented early postvaccination sera (p < 0.001). Children with
      naturally acquired immunity had significantly higher titres than children with
      vaccine-induced immunity titres (p < 0.001). After revaccination of the
      previously vaccinated children, a significant booster rise was seen (p < 0.001).
      After revaccination of children with naturally acquired immunity, no significant
      booster effect was observed. Sixty-five children of the 332 (20%) previously
      vaccinated children had no or borderline measles titres prior to the booster. The
      study suggests that the vaccine-induced measles antibodies decline with time and
      may fall under the protective level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147094
TI  - Immunogenicity in guinea-pigs of a crude ribosomal fraction from Microsporum
      canis.
AB  - The immunogenicity of a crude ribosomal fraction (CRF) extracted from Microsporum
      canis was tested by assessing protection of vaccinated guinea-pigs (GP) against a
      challenge with the dermatophyte. Stimulation of the humoral as well as the
      cellular immune systems of these animals was evaluated by ELISA and the
      lymphocyte stimulation tests, respectively. In addition, the immune response
      elicited by the M. canis CRF was examined for cross-reactivity towards
      Trichophyton verrucosum antigen. The duration of the infection induced by M.
      canis in GP was reduced to 8 days in vaccinated animals versus 37 days in the
      control GP. Both humoral and cellular immune systems were stimulated by the CRF.
      Sera of GP vaccinated with M. canis CRF revealed presence of anti-T. verrucosum
      antibodies, albeit at titres significantly lower than against M. canis.

PMID- 8147095
TI  - Safety and immunogenicity of a purified haemagglutinin antigen in very young high
      risk children.
AB  - Forty-three high-risk preterm children received either one of three doses of
      purified hemagglutinin antigen (HA) (7.5 micrograms/0.25 ml, 22.5 micrograms/0.25
      ml or 67.5 micrograms/0.25 ml) or standard split product vaccine (ST) (22.5
      micrograms/ml dose) over the 1990-1991 influenza season. Components for all
      vaccines included A/Shanghai 16/89, A/Taiwan 1/86 and B/Yamagata 16.88. Sera for
      antibody was drawn before, 6 weeks and 4 months after the first vaccine dose. The
      study was randomized and blinded. All children received two 0.25 ml doses of
      vaccine 4 weeks apart. No significant local or systemic reactions occurred. Six
      weeks after the first dose, children receiving ST vaccine had significantly
      higher seroconversion rates to A/Shanghai (p = 0.03) and to A/Taiwan (p = 0.01)
      than did those receiving equivalent HA vaccine. However, seroconversion rates
      were significantly higher for those children receiving the highest HA dose. All
      four vaccine groups responded poorly to B/Yamagata. Geometric mean titres were
      low for all groups and declined over 4 months. These results suggest that the
      equivalent dose of HA vaccine offers no advantage over ST vaccine in the
      immunization of high-risk preterm children.

PMID- 8147096
TI  - Further studies on the efficacy of an inactivated African horse sickness serotype
      4 vaccine.
AB  - The immunity induced by two inoculations of a commercial inactivated African
      horse sickness (AHS) serotype 4 (AHSV-4) vaccine was studied. No adverse reaction
      was observed in five horses following vaccination. Following challenge
      inoculation, no clinical signs attributable to AHS, no viraemia indicating
      infection, and no anamnestic response was observed in the vaccinated ponies. Two
      control ponies developed clinical signs typical of AHS, high levels of viraemia,
      and died 7 and 8 days postchallenge-inoculation. The quality of immunity induced
      by the two-dose regimen was compared with a one-dose regimen from a previous
      study; in the one-dose study following challenge-inoculation, six of nine ponies
      were protected from clinical signs of AHS, seven of the nine vaccinated ponies
      developed an anamnestic response, and one pony had a viraemia about 10(3) 50%
      mouse lethal dose of AHSV-4 per ml of blood for 3 days following challenge
      inoculation. The utility of an efficacious inactivated AHS vaccine in the control
      and eradication of AHS from a non-endemic area is discussed. The lack of viraemia
      following vaccination with an inactivated vaccine and the prevention of vector
      infection by animals exposed to field virus are important in the eradication of
      AHS.

PMID- 8147097
TI  - Truncated bovine herpesvirus-1 glycoprotein I (gpI) initiates a protective local
      immune response in its natural host.
AB  - Current modified live and killed BHV-1 vaccines have not reduced the incidence of
      bovine herpesvirus-1 (BHV-1), the principal viral agent in bovine respiratory
      disease complex. The requirement for production of viral proteins for immune
      study has resulted in the establishment of a cell line which constitutively
      expresses BHV-1 gpI. A truncated BHV-1 envelope gpI protein was secreted into the
      culture supernatant of D17 cells transfected with the gpI gene lacking the coding
      sequence for the transmembrane region (TMR). The transmembrane domain is
      essential for gpI stability in the envelope, virus infectivity and, most
      probably, natural killer cell recognition; however, we have tested the
      possibility that this domain is not required for inducing an adaptive, protective
      immune response. Immunization of calves with this truncated gpI protein induced
      gpI-specific nasal IgA, IgG1, serum neutralizing antibodies and gpI-specific
      peripheral lymphocyte proliferation. All immunized calves were protected from
      clinical disease after BHV-1 challenge. Further, nine of ten immunized calves had
      no intranasal viral shedding. One animal shed a minimal amount of virus following
      challenge, but produced no antibodies to other viral proteins as evidenced by
      immunoprecipitation of 35S-labelled viral proteins by sera from virus-challenged
      animals. This study represents the first evidence that a recombinant truncated
      gpI subunit vaccine can confer local mucosal immunity and establish a strong
      protective barrier against disease caused by BHV-1 in the natural host. Also,
      these data demonstrate the feasibility of preventing initial viral replication in
      the host and distinguishing vaccinated from wild-type virus-infected animals.

PMID- 8147099
TI  - Comparison of influenza serological techniques by international collaborative
      study.
AB  - An international collaborative study was performed to investigate the
      reproducibility of influenza serological techniques. Participants in seven
      laboratories representing five countries measured antibody to A/Sichuan/2/87
      (H3N2), A/Taiwan/1/86 (H1N1) and B/Beijing/1/87 influenza viruses in 11 human
      sera and three postinfection ferret sera. Two different serological techniques
      were used, haemagglutination inhibition (HI) and single-radial haemolysis (SRH)
      and, although each technique was reproducible within laboratories, variability
      between laboratories was higher for HI (maximum variability 32-fold; geometric
      coefficient of variation, GCV, 112%) than for SRH (maximum variability 3.8-fold;
      GCV 57%). The use of a standard serum allowed direct comparison of HI and SRH
      data and, for each technique, a standard serum improved inter-laboratory
      agreement. For influenza A viruses there was a correlation between HI and SRH
      antibodies (correlation coefficient approximately 0.9). An HI titre of 1:40 in
      human sera corresponded to an SRH titre of 19-33 mm2. The results of the study
      indicate that two sera would be expected to contain different antibody levels if
      their HI titres differed by > fourfold and SRH areas differed by > 50%. Both SRH
      and HI possessed equivalent sensitivity for measurement of antibody to influenza
      A viruses but SRH was more sensitive for detection of antibody to influenza B
      viruses. The study provided valuable information about standardization of
      antibody assays.

PMID- 8147098
TI  - Cytotoxic T lymphocyte response in mice induced by a recombinant BCG vaccination
      which produces an extracellular alpha antigen that fused with the human
      immunodeficiency virus type 1 envelope immunodominant domain in the V3 loop.
AB  - The host immune response of cell-mediated immunity, particularly that of
      cytotoxic T lymphocytes (CTLs), is a major immune defence mechanism which may
      provide resistance to a human immunodeficiency virus type 1 (HIV-1) spread
      leading to acquired immune deficiency syndrome (AIDS). To prevent the
      accompanying activity of HIV-1 proteins responsible for the loss of helper T
      lymphocyte function, it is crucial to develop a live attenuated recombinant
      vaccine expressing only T- or both T- and B-cell epitopes. Here, we examined the
      expression of the HIV-1 Env protein V3 region (15 amino acids from Arg315 to
      Lys329) in Mycobacterium bovis BCG as a fused form with an extracellular alpha
      antigen of Mycobacterium kansasii. Balb/c mice inoculated with this recombinant
      BCG (rBCG), rapidly induced V3 peptide-specific CTLs. Target cell lysis was
      restricted to the murine class I major histocompatibility complex, H-2d. A
      similar CTL response was also elicited after Balb/c mice were immunized with the
      same rBCG even when pre-inoculated with non-recombinant BCG. Thus, the rapid
      induction of HIV-1-specific CTLs indicates that this vaccine may be a therapeutic
      approach to preventing progression to AIDS.

PMID- 8147100
TI  - MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide, inhibits the
      metastasis of haematogenous and non-haematogenous tumours in mice.
AB  - The antimetastatic effects of MDP-Lys(L18), a lipophilic derivative of muramyl
      dipeptide (MDP), against three different types of highly metastatic murine tumour
      cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 T lymphoma, were
      examined in C57BL/6, Balb/c and CDF1 mice, respectively. The administration of
      100 micrograms of MDP-Lys(L18) 2 or 4 days before tumour inoculation led to a
      significant decrease in lung metastasis of B16-BL6 melanoma or colon 26-M3.1
      carcinoma cells. MDP-Lys(L18) was also effective in the inhibition of liver
      metastasis of L5178Y-ML25 lymphoma cells by administration 2 or 4 days before
      tumour inoculation. The prophylactic effect of 100 micrograms of MDP-Lys(L18) on
      tumour metastasis was evident for the different administration routes, i.e.
      subcutaneous, intravenous or intranasal injection, or oral administration. It is
      of prime interest that oral administration of 1 mg of MDP-Lys(L18) induced a
      significant decrease in lung metastasis of B16-BL6 melanoma cells. Administration
      of MDP-Lys(L18) 4 days before assay led to induction of tumoricidal activity by
      peritoneal macrophages and growth inhibition by the sera against B16-BL6 or L929
      cells. When MDP-Lys(L18) was subcutaneously administered five times after tumour
      inoculation to test therapeutic effect in an experimental and spontaneous
      metastasis model using B16-BL6 melanoma, the consecutive administrations of MDP
      Lys(L18) significantly inhibited lung metastasis in tumour-bearing mice. These
      results suggest that MDP-Lys(L18) is able to enhance host resistance to reduce
      tumour metastasis and is a potent immunomodulating agent which may be applied
      prophylactically or therapeutically for the treatment of cancer metastasis.

PMID- 8147101
TI  - A trial of the synthetic malaria vaccine SPf66 in Tanzania: rationale and design.
AB  - The development of a safe, affordable and effective malaria vaccine to form part
      of control schemes in malaria endemic countries is a priority for researchers and
      public health officials. SPf66 is the first malaria vaccine to have shown partial
      protection against natural challenge in a phase III trial carried out in a
      hypoendemic area of Colombia. This paper describes the rationale and design of
      the first field trial of SPf66 outside South America, and the first to be
      conducted in an area of high perennial transmission.

PMID- 8147102
TI  - Relationship between protein adsorptive capacity and the X-ray diffraction
      pattern of aluminium hydroxide adjuvants.
AB  - Thermal treatment during the preparation of aluminium hydroxide adjuvants affects
      the primary crystallite size of the adjuvant. The primary crystallite size can be
      characterized by the line broadening of the (020) reflection of the X-ray
      diffraction pattern. Studies of protein adsorption using bovine serum albumin as
      a model protein revealed a direct relationship between the albumin adsorptive
      capacity and the width at half height (WHH) of the (020) reflection in the X-ray
      diffraction pattern.

PMID- 8147103
TI  - SPf66: research for development or development of research?

PMID- 8147104
TI  - [International Journal of Food Research and Technology].

PMID- 8147105
TI  - Perinatal epidemiology in Switzerland.

PMID- 8147106
TI  - Classification of perinatal deaths.

PMID- 8147107
TI  - Reproductive and perinatal epidemiology using official statistics: what future
      for Switzerland?

PMID- 8147108
TI  - Do we need more or different information to evaluate perinatal care in
      Switzerland?

PMID- 8147109
TI  - Comparing home to hospital deliveries: recruitment, referrals and neonatal
      outcome.

PMID- 8147110
TI  - Respiratory distress syndrome in Switzerland: comparison of the 1984 with the
      1974 data.

PMID- 8147111
TI  - The uses of epidemiology in the evaluation of regional perinatal services.

PMID- 8147112
TI  - Extremely low birthweight infants in Switzerland: a database of the Swiss
      neonatology group.

PMID- 8147113
TI  - [High number of multiple births in Switzerland 1985-1988].

PMID- 8147114
TI  - Objectives of obstetrical data collection.

PMID- 8147115
TI  - Is there a need for a computerised neonatal system?

PMID- 8147116
TI  - Population-based study of the incidence and prevalence of significant handicaps
      in children (canton of Vaud).

PMID- 8147117
TI  - Vertically transmitted HIV infection: how representative are data from a
      voluntary registry? Pediatric AIDS Group of Switzerland (PAGS).

PMID- 8147118
TI  - [Survey of the management of asymptomatic newborn infants with a risk for
      infection at birth].

PMID- 8147119
TI  - Congenital anomalies in Switzerland: problems and solutions in data collection
      and their European integration experiences by Eurocat (Switzerland).

PMID- 8147120
TI  - Prevalence of retinopathy of prematurity in Switzerland.

PMID- 8147121
TI  - Perinatal epidemiology in Switzerland. Agenda for the future.

PMID- 8147122
TI  - [Vaccination coverage of 2-year-old children in Geneva].
AB  - OBJECTIVE: To measure the immunization uptake among 2 year-old children living in
      Geneva. METHODS: Review of the vaccination cards, systematically checked because
      of the compulsory vaccination against diphtheria, during the year in 1991.
      RESULTS: 3937 immunization cards were reviewed, ie. 93.6% of the children in the
      given age group. Immunization uptake rates were, for diphtheria and tetanus (3
      doses) 96.8%; pertussis (3 doses) 96.1%; poliomyelitis (3 doses) 96.6%. For
      measles, mumps and rubella vaccine (MMR) (1 dose), 78.4%. For the Haemophilus
      influenzae b vaccine, recently introduced: 68.5%. The uptake rate for MMR was
      lower among children of swiss origin (75.5%) than among children of other
      nationalities (84.6%, p < 0.0001). The highest rates were found among children
      coming from southern Europe and Latin America. CONCLUSIONS: From the point of
      view of the community risk, immunization uptake rates for diphtheria, tetanus,
      pertussis and poliomyelitis can be considered satisfactory. For MMR vaccine, the
      rate was higher than 2 years earlier, but still insufficient, compared to the
      level which could block the transmission of the target diseases in the
      population. The persistence of such a low rate of immunization uptake will not
      prevent the occurrence of epidemics in the population.

PMID- 8147123
TI  - [The new specialist graduate education regulation].

PMID- 8147124
TI  - [Learning to read and write in compulsory education: a longitudinal study of the
      incidence and stability of reading and writing difficulties in a Vienna school
      district].
AB  - In a longitudinal study, the development of reading and spelling skills was
      analyzed in about 500 Viennese school children from first through eighth grade.
      Performance in reading and spelling was tested at least once a year through grade
      four and then again at the end of eighth grade using standardized reading and
      spelling tests. The differences among the children in reading and spelling skills
      were found to be very stabile over time, and if there was difficulty with reading
      and spelling early on this usually persisted. Only a few of the children who had
      problems with reading in second grade improved enough so that they attained
      average scores at the end of eighth grade. The poorest readers read at the same
      level at the end of fourth grade as average readers did at the end of first
      grade. At the end of eighth grade these children had attained the level of
      average readers at the end of second grade. Similarly, poor spellers showed less
      improvement over time than children with average spelling skills. By the end of
      eighth grade these children had fallen way behind their peers.

PMID- 8147125
TI  - [Behavioral problems in children of Turkish guest workers in Vienna].
AB  - This paper describes the behaviour disturbances and emotional problems of Turkish
      immigrant children aged 9 to 13 years living in Vienna. The children's behaviour
      was rated with Rutter's scales and the relationship of the results to any
      language problems, the socioeconomic situation and the sociocultural background
      of the immigrant families was then analyzed. A consecutive series of 111 Turkish
      and 25 Austrian children were rated by their parents and by both Turkish- and
      German-speaking teachers. Psychiatric symptoms of the children's parents were
      assessed with the symptom checklist SCL-90. The prevalence of behavior problems
      did not differ between the Turkish and Austrian children, who were of similar
      social class. The most common symptoms were restlessness, overactivity, poor
      concentration and anxiety. Whereas socioeconomic and sociocultural factors did
      not influence the frequency or severity of behavior problems in the Turkish
      children, there was a highly significant relationship between behavior problems
      and problems with German or Turkish. Moreover, the children very frequently had
      problems with both languages. Therefore intervention strategies with such
      children should focus on the language problems.

PMID- 8147126
TI  - [Comorbidity of substance abuse and antisocial behavior. Analysis of an
      adolescent psychiatric population].
AB  - Comorbidity, the simultaneous occurrence of different psychiatric disorders, is a
      common phenomenon in child and adolescent psychiatry. Usually, it affects the
      prognosis negatively. For example, drug abuse increases the risk of drug
      dependency among adolescents with conduct disorders. In this study, a high-risk
      group of 30 adolescents with conduct disorders at a regional psychiatric hospital
      was examined regarding drug abuse. Half of the adolescents were taking drugs.
      This influenced the course in a way which limited the therapeutic possibilities.
      The comorbidity of drug abuse and conduct disorders is discussed in connection
      with prevention.

PMID- 8147127
TI  - [Genetics of reading-spelling difficulties].

PMID- 8147128
TI  - [Can self-injury be viewed as an addictive behavior in adolescents? Aspects of
      the pathogenesis of self-injury behavior].

PMID- 8147129
TI  - [Therapeutic and pedagogic help for emotionally handicapped children and
      adolescents according to KJHG reform].

PMID- 8147130
TI  - [Comment on J. Martinius: Periodic psychosis in adolescence].

PMID- 8147131
TI  - [Present and future therapeutic strategies in rheumatoid arthritis].
AB  - The triad of inflammation, immunoproliferation and synovial hyperplasia is
      recognized in the pathogenesis of rheumatoid arthritis, however, the sequence of
      events remains as highly controversial as ever. The "RA pyramid" was established
      on the assumption that inflammation is at the top with the destructive processes
      as sequelae. The moderate successes achieved by conservative therapy with regard
      to long-term outcome cast doubt on this hypothesis. Inhibitors of prostaglandin
      synthesis have not been and are not disease modifying. Do substances which
      influence the endothelial adhesion molecules or leucocyte adhesion receptors
      (leumedines) promise to be more successful? Do the empirically developed disease
      modifying antirheumatic drugs (Gold parenteral, MTX) have to be administered
      earlier? Unfortunately, there is a need for a differential diagnosis which is
      prognostically valid with regard to the dynamics and aggressiveness of rheumatoid
      arthritis. Moreover, a pharmacological basis for optimally founded combination
      strategies is also lacking. Presently, the emphasis of research is directed at
      the regulation of dysfunctional immune systems. Immunosuppressives (cyclosporin
      A), cytokine antagonists, receptor antagonists and soluble cytokine receptors (IL
      1, IL-6, TNF-alpha), antibodies against lymphocyte subgroups (CD4, CD7) or
      against cytokines and their receptors are part of the arsenal for the medium
      term. Too little is still known about the role of protective cytokines (TGF-beta,
      IL-4, gamma-INF). Currently, however, it is prognosticated that these targeted
      therapies will only succeed in RA subgroups or only in intelligent combinations.
      More attractive alternative are strategic therapy modalities which intervene very
      early in the pathological process, such as the modulation of antigen presentation
      (MHC blocking peptides, T-cell receptor antagonists, T-cell vaccination) or the
      induction of tolerance against autoantigens through the oral administration of
      antigens (collagen II, HSP's, OM-8980). If the center of the pathological
      process, however, is found in the synovial proliferation of tumor-like cell
      clusters, then there are only a few years at the beginning of the disease when
      there is a real chance to impede destruction. In this case, aggressive induction
      therapy can be the only key to success. In the future, specifically active
      cytostatics (inhibitors of angiogenesis) will have to be developed and clinical
      trials conducted on adjuvant therapies with substances which strengthen bone and
      cartilage, making them more resistant to aggressive cell clusters
      (bisphosphonates, calcitonins, metalloproteinase- or collagenase-inhibitors).

PMID- 8147132
TI  - [Expression of TNF receptors in rheumatoid arthritis and ankylosing spondylitis].
AB  - Tumor necrosis factor is an important mediator of the pathophysiologic events in
      synovitis. The expression of the p75 and p55-TNF-receptors in rheumatic diseases
      was investigated. Synovial mononuclear cells (SMNC) of patients with rheumatoid
      arthritis and spondylarthropathies express p75 TNF receptors in all cases,
      whereas SMNC of patients with traumatic synovitis do not. In 4/9 patients with
      rheumatoid arthritis and in 6/11 patients with spondylarthropathies SMNC also
      expressed the p55 TNF receptor. Differential analysis of lymphocytes and
      monocytes/macrophages revealed that both predominantly expressed the p75 TNF
      receptor. The highest concentrations of both soluble TNF receptors which may act
      as TNF antagonists were found in synovial fluids of rheumatoid arthritis
      patients.

PMID- 8147133
TI  - [Arthroosteitis pustulosa, spondarthritis hyperostotica pustulo-psoriatica, SAPHO
      syndrome: clinical experiences and review of the literature].
AB  - Pustulotic arthroosteitis is characterized by the association of inflammatory and
      hyperostotic skeletal changes, primarily of the anterior chest wall, and chronic
      recurrent skin lesions of the palms and soles known as pustulosis palmaris et
      plantaris. Since its first description by Sonozaki in 1981 in Japan, it has also
      been reported by several European authors and become widely accepted as a
      separate entity within the spectrum of the seronegative spondylarthropathies. In
      this report, we describe 11 cases seen in our clinic in the years 1985 to 1992.
      Course and severity of the disease varied greatly among individual patients. In
      four of them a difference of up to 6 years between the onset of skin and skeletal
      symptoms were noted. Besides chronic recurrent nonspecific osteomyelitis in two
      cases, neither an association to other rheumatic or dermatologic diseases nor to
      HLA-B27 could be found. Corticosteroids, non-steroidal anti-inflammatory drugs,
      immunosuppressive agents, and antibiotics were all used with uncertain
      therapeutic success. Based on these data, we suppose that pustulotic
      arthroosteitis is more common in Germany than previously thought, and has to be
      considered as an important differential diagnosis of sternoclavicular arthritis.
      In a review of the available literature, the current opinions on nomenclature,
      etiology, pathogenesis, and treatment are discussed.

PMID- 8147134
TI  - [Palmoplantar keratosis and hyperostotic spondylosis--an associated syndrome?].

PMID- 8147135
TI  - [Rheumatoid factor activity, age at manifestation and roentgenologic progression
      of rheumatoid arthritis--a retrospective study].
AB  - The outcome of RF-activity (measured by hemagglutination in the modification of
      Podliachouk-Harboe) was investigated in 95 patients with RA. In 52 of these
      patients the radiological progression (modification of Larsen index for hands and
      feet) in correlation to the outcome of RF was assessed. The results can be
      summarized in the following way: 1. Elderly RA patients show a significant
      elevation of RF titer. 2. There is a statistically insignificant correlation
      between age of RA manifestation and RF level. 3. The investigation of individual
      RF outcome shows that 54% of the patients have a relatively constant RF level,
      15% tend to a decrease of the level of RF activity. Increased RF activity could
      only be demonstrated in 31% of the patients in the follow-up. 4. We more often
      observed a decrease of RF activity in RA cases with a disease manifestation < 30
      y. We found no significant decrease in the follow-up in cases with manifestation
      > 60 y. 5. RA patients with a high level of RF activity (HAR > 1:512) have a
      significantly higher radiological progression index than cases with a low RF
      activity (HAR < 1:512).

PMID- 8147136
TI  - [Costs and financial feasibility of long-term drug therapy of chronic
      polyarthritis].
AB  - The annual costs of the most common basic therapies in Germany will be analyzed.
      The costs in Deutsche marks will be divided as drug charges, physician charges
      and laboratory expenses. There are significant price differences also in
      equipotent preparations.

PMID- 8147137
TI  - [Genetic or psychogenic. On the heredity-environment question of psychogenic
      diseases].
AB  - In the introduction the problems of and access to human genetical gains of
      knowledge are described, especially the research theoretical paradigm of the
      classic twin method. The article shows: In the last decades with the help of twin
      research hereditary determinants have been found also for many (so-called and
      predominantly) psychogenic illnesses: For personality disorders, for
      psychoneurosis as well as for several psychosomatic illnesses. In the sense of a
      complementary list--more psychogenic/environmentally determined or primarily
      somatically/hereditarily determined--several normal characteristics and clinical
      pictures are listed.

PMID- 8147138
TI  - [Results of psychoanalytic therapy].
AB  - Within a naturalistic design 44 psychoanalytic treated patients are examined with
      regard to qualitative and quantitative outcome. The results are compared to 56
      dynamic and 164 inpatient therapies. A comparison of symptoms, diagnoses and
      motivation before therapy leads to the conclusion that there are very different
      patient groups treated within this different settings. Therefore randomization
      seems to be an inadequate strategy to compare groups in different therapeutic
      settings. Using different criteria of outcome it can be demonstrated that
      psychoanalytic treated patients improve very well and to a larger extent than
      psychodynamically treated patients or inpatients. Different criteria of outcome
      and different observing perspectives (patient/therapist) lead to interesting
      results. Patients report primarily improvements in somatic, anxiety and
      depressive complaints. Therapists moreover report substantial improvements in
      interactional symptoms and behaviour. The different results in using several
      criteria are presented and discussed with regard to the methodology of outcome
      measurement. Finally recommendations for further studies in the psychoanalytic
      context are presented.

PMID- 8147139
TI  - [The Freuds and the Bernays: 2 Jewish families].
AB  - Freud's life and work was largely determined by the support he gained through the
      union with Martha Bernay. The family constellation between Freud and Martha is
      described in the light of the historical developments of the fates the
      generations of the Freud family and the Bernay family. Freud was the grandson of
      a poor and little educated galician travelling Jew, whose family was still
      subject to the humiliating laws for the Jews of the Austrian-Hungarian monarchy-
      especially the family laws. Martha was the granddaughter of the famous and very
      much respected rabbi Isaac Bernay of Hamburg who was honoured with the title
      Chacham--the wise one. He had given his congregation a new name and in his battle
      against reform-Judaism had finally proclaimed the cherem--the great ban--against
      certain representatives of this reform-Judaism. It is discussed how these family
      historical influences shaped Martha and made it possible for her to accompany her
      husband in his fight for the psychoanalytic movement.

PMID- 8147140
TI  - ["The most ill go into psychoanalytic treatment"? Critical comments on an article
      in Report Psychologie].
AB  - Thomas and Schmitz claim that they "deliver a proof for the effectiveness of
      humanistic methods" (p. 25) with their study. However, they did not or were not
      able to verify their claim due to several reasons: The authors did not say if and
      if so to what extent the treatments carried out within the framework of the TK
      regulation were treatments using humanistic methods. The validity of the only
      criterium used by the authors, the average duration of the inability to work,
      must be questioned. The inferential statistical treatment of the data is
      insufficient; a non-parametrical evaluation is necessary. Especially missing are
      personal details concerning the treatment groups (age, sex, occupation, method,
      duration and frequency of therapy), which are indispensable for a differentiated
      interpretation. In addition there are numerous formal faults (wrong quotations,
      mistakes in tables, unclear terms etc.). In view of this criticism we come to the
      conclusion that the results are to a large degree worthless, at least until
      several of our objections have been refuted by further information and adequate
      inferential statistical methods. This study is especially unsuitable to prove a
      however defined "effectiveness of out-patient psychotherapies", therefore also
      not suitable to prove the effectiveness of those treatments conducted within the
      framework of the TK-regulation and especially not suitable to prove the
      superiority of humanistic methods in comparison with psychoanalytic methods and
      behavioural therapy.

PMID- 8147141
TI  - [Phase-specific function of denial in type 1 diabetic patients after disease
      onset].
AB  - In a longitudinal study we examined 43 patients with type 1 diabetes one week
      after onset as well as 8 and 24 month later in order to analyze the psychological
      role of denial processes in correlation to metabolic functions. Only depression
      decreased over the studied period while coping and denial remained stable.
      However, the adaptive function of denial after onset with low anxiety, good
      coping and few complaints became maladaptive over the first two years and the
      correlation of denial with a centripetal kinship behavior loosened. The
      destructive effect of denial was indicated only by delayed requests for
      assistance while no correlation could be shown for phase-specific internal
      restructuring of the psychological function of denial to compliance and metabolic
      control.

PMID- 8147142
TI  - [Specific characteristics of Crohn disease patients--results of a cluster
      analysis of personality markers].
AB  - The aim of this study was to find out, if patients with Crohn's disease share
      some personality traits or if it makes more sense to separate them into
      subgroups. Therefore, 52 patients took part in a psychoanalytic interview. The
      interview was composed in order to check personality characteristics as they were
      named in the literature. However, there could not be found any specific
      personality traits, but a cluster analysis revealed 7 subgroups. Two larger
      subgroups, together 22 patients, consisted of patients with inhibited aggression,
      who were closely connected to their families and showed illness inciting
      stressful life events. Another subgroup, 11 patients, showed a marked
      independent, aggressive and illness-dissimulating behavior. The hypothesis of a
      specific personality structure has to be rejected.

PMID- 8147143
TI  - [Down with the novel in presenting psychoanalysis--long live interactional
      history].

PMID- 8147144
TI  - [Endoscopic surgery of the upper gastrointestinal tract].
AB  - Clinical application of laparoscopic cholecystectomy was followed by a lot of
      other endoscopic procedures for the surgical treatment of diseases of the upper
      gastrointestinal tract. In cases of disorders of esophageal motility traditional
      procedures can be performed endoscopically. Remarkable experiences were published
      concerning the cardiomyotomy, and fundoplication. Endoscopic operations could be
      shown to be a suitable treatment of benign and malignant tumours of the
      esophagus. Also the nowadays very rarely indicated vagotomy can be performed
      laparoscopically having good results. During the last year a few new operations
      could be added by using endoscopic linear staplers for resections and anastomoses
      such as gastostomies, jejunostomies, gastroenterostomies and even BII resections.
      In general surgeons are enabled to perform a great variety of procedures by the
      use of endoscopic techniques.

PMID- 8147145
TI  - [Value of laparoscopy in diagnosis and therapy of the acute abdomen].
AB  - While diagnostic laparoscopy is a well established tool, therapeutic laparoscopy
      for acute abdominal disorders has recently been made possible by video-endoscopic
      techniques. From July 1989 to April 1992, 243 laparoscopic interventions were
      carried out in patients with an acute abdomen. After a pilot phase, patients with
      acute appendicitis were entered into a randomized trial, those with acute
      cholecystitis were operated within the next day list. Among the 243 operations
      were 202 appendectomies, 12 closures of perforated peptic ulcers, 4 successful
      interventions for intestinal obstruction, 4 irrigations for intraabdominal
      abscesses and 35 further operations, some of which had to be finished as
      laparotomies. Laparoscopic appendectomy was less painful but technically more
      difficult. In cases which needed bowel resection for ischemic necrosis or
      diverticular disease, conversion to open surgery had to be performed.
      Laparoscopic treatment of acute abdominal disorders including peritonitis can be
      effective and beneficial in one out of two patients. Adequate surgical training,
      expertise and respect to the safety of the patient are mandatory. The application
      of endoscopic suture devices will further enlarge the spectrum of laparoscopic
      treatment options for the acute abdomen.

PMID- 8147146
TI  - [Does laparoscopic appendectomy have advantages? Laparoscopic appendectomy in
      comparison with conventional appendectomy--an observational study during
      introduction of laparoscopy].
AB  - From October 1990 to October 1992 the first 23 laparoscopically operated patients
      were recorded. 11 patients retrospectively including a supplementary questioning
      to missing data, 12 patients prospectively with a follow-up 6-8 weeks later. They
      were compared with 35 from April 1991 to April 1992 conventionally operated and
      prospectively observed patients. Laparoscopy was performed on patients with
      subacute clinical signs. The median age was comparable. Acute appendicitis was
      histologically confirmed in 18% of the laparoscopically and in 80% of the
      conventionally operated patients. Operating time was in mean 110 minutes for
      laparoscopic and 65 minutes for open appendectomy. The postoperative
      complications for laparoscopy included 4 Douglas abscesses (2 x open and 2 x
      pararectal revisions), one peritonitis due to a defect Roeder-loop and an
      haematoma of the abdominal wall. One case of wound infection (3%), one pericoecal
      abscess which needed an ileoascendostomy and a postoperative fatigue syndrome
      were recorded for open appendectomy. The postoperative return to normal diet was
      faster for laparoscopy. Return to normal bowel habits, the need of analgesia and
      the nominal analogue scales concerning pain, quality of sleep, well-being and
      appetite showed no obvious differences between the two operation methods. The
      postoperative stay was on average 6.7 days for laparoscopy and 5.6 days for the
      open operation. The results show the severe complications which may happen when
      introducing this new operation method. The laparoscopic appendectomy should only
      be performed electively in subacute appendicitis or when diagnostic exploration
      shows an inflamed appendix. Careful rinsing of the operation site and
      perioperative antibiotic treatment are mandatory. We made good experiences when
      using a stapler for the removal of the appendix.

PMID- 8147147
TI  - [Ultrasound dissection in laparoscopic cholecystectomy].
AB  - An ultrasound dissector especially developed for laparoscopic surgery was used
      during laparoscopic cholecystectomy on 34 patients. The ultrasound power, the
      volume of suction and irrigation could be determined individually at the
      generator and activated during the operation with a foot pedal. With the
      dissector it was possible to fragmentate, emulgate and aspirate simultaneously
      fat tissue as well as infected edematous structures. The cystic artery and cystic
      duct, small vessels, lymphatic and connective tissue were not damaged. Therefore
      this system seems to be excellent for the preparation of Calot's trigonum and
      blunt dissection of the gallbladder out of its bed, particularly in fatty, acute
      or chronic infected tissue. No complications were observed within the peri- and
      postoperative period.

PMID- 8147148
TI  - [Minimally invasive surgery of the colon and rectum].
AB  - In the period from 1.8.89 to 1.7.92 140 adenomas and 63 carcinomas were locally
      resected from the rectosigmoid area with the instruments of TEM. The mortality
      was 0.5%, the rate of dehiscence of the suture 9.8%. 75% of these were treated
      conservatively. One of the 29 patients with locally resected pTl-low risk
      carcinoma developed a recurrence so far. The rate of recurrent adenomas was 1.4%.
      From 7.1.1992 to 24.5.1993 21 procedures in colorectal surgery were performed
      laparoscopically or in a combined laparoscopic transanal operation. The mortality
      was zero. 1 case of suture dehiscence, 2 cases of crural phlebothrombosis and 1
      lesion of the left ureter were observed. The use of TEM in the combined procedure
      means an extension of the range of minimally invasive colorectal surgery to the
      lower rectum.

PMID- 8147149
TI  - [Critical evaluation of laparoscopic hernia surgery].
AB  - The success of the laparoscopic cholecystectomy was remarkable and well-founded,
      thus it seems necessary to examine whether this procedure could be also used for
      other general surgical operations. Since Dec. 29th, 1990 the transperitoneal
      repair of hernias by laparoscopy has been performed in 177 patients. The patients
      were followed up in regular intervals. The first 100 patients were treated with
      the "plug repair" technique of Schultz and Corbitt. In this group one recurrence
      (4 month after operation) and one dislocation of a mesh roll (2 weeks after the
      operation) were observed. In the middle of April 92 we changed the laparoscopic
      operation technique to a preperitoneal mesh fortification analogous to the
      procedure of Stoppa. This requires a detailed preparation of all possible
      positions of the hernia (medial and lateral compartment). A cutting through all
      layers of the abdominal wall can be avoided. After the preparation all abdominal
      wall defects can be fortified effectively and clearly. In this group we have
      treated 77 patients, so far without complications. With the exception of scrotal
      hernias and adhesions the laparoscopic hernioplastique can be used in any
      indication of inguinal hernia repair. An evaluation of the long-term results can
      only be performed in the future although the early results are encouraging.

PMID- 8147150
TI  - [Laparoscopic hernia surgery].
AB  - While classical inguinal hernia repair has recently been brought up for
      discussions among surgeons, at present various modified techniques are being
      reintroduced in general surgery. Surgical hernia repair techniques which partly
      are known since several decades are being carried out laparoscopically since
      1989. Between August 1992 and June 1993, the authors performed 52 laparoscopic
      inguinal hernia repairs using the preperitoneal placement of nonresorbable mesh.
      There were no intraoperative complications. Merely one patient had an abdominal
      wall hematoma at the site of a trocar which resolved spontaneously. All patients
      have been followed up for 3-13 months. To date, all postoperative check ups
      revealed no recurrences, testicular atrophy or paresthesia. Even though little
      can yet be said regarding long-term results especially about recurrences,
      laparoscopic preperitoneal hernia repair seems to be a promising surgical
      procedure concerning early postoperative results.

PMID- 8147151
TI  - [Evaluation of the Bassini reconstruction principle for inguinal hernia].
AB  - In a prospective study, 100 adult male patients with clinically diagnosed
      inguinal hernias underwent surgery. The operation method was the Bassini repair.
      The operation always included splitting of the transversal fascia, that after
      review of the relevant literature obviously is not part of the usual applied
      operation technique. Therefore the "Bassini method" could be falsely afflicted
      with a relatively high recurrence rate. At the follow up clinical examination,
      performed at least 1 year after surgery, a 3.8% recurrence rate was found. It can
      be recommended that it should be continued to apply Bassini repair to all types
      of inguinal hernias. A classification of posterior inguinal wall is suggested:
      under poor anatomical conditions, i.e. "used" fascia transversalis and "elevated"
      internus muscle a three-fold risk of recurrence can be expected. In this
      situation the operative correction according to Bassini should be avoided and a
      procedure to repair or cover the defect should be performed first.

PMID- 8147152
TI  - [Technological characteristics of endoscopic high frequency current and laser
      interventions].
AB  - High frequency current and laser radiation perform two possibilities to generate
      therapeutic and surgical heat. The integration of these two technologies into
      endoscopy resulted in important ancillary techniques in the hands of a surgeon.
      Starting from the principal methods for coagulation and dissection of tissue the
      respective technological aspects at the interaction of high frequency currents
      and intensive laser radiation with different wavelengths on biological tissue are
      illustrated. Mono- and bipolar HF-techniques as well as the light-guide assisted
      laser method in the contact and non-contact mode are explained. The special
      problems in endoscopy arising from the reduction in visibility by haemorrhages
      and the development of smoke at the thermally induced coagulation may be overcome
      successfully by the simultaneous instillation of a nearly isolating liquid during
      the HF-treatment. The so-called electrohydrothermosation (EHT) method is
      presented and several probes and instruments for endoscopic hemostasis and
      microsurgery are explained. For an increase in safety at the endoscopic
      application of HF-current the use of the bipolar technique is recommended and
      several technological developments used in this mode are pointed out. It is shown
      that the absorption of radiation through the water-content of the tissue is
      mainly responsible for the reactions which may be produced with laser-light.
      Furthermore it is mentioned that the range of lasers which might be used has a
      large spectrum of medical applications which had been even increased especially
      by the new erbium and holmium solid state lasers.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8147153
TI  - [Repair procedures in surgery of inguinal hernia in their historical evolution].
AB  - The last decades have witnessed a great number of "novelties" published for
      inguinal hernia surgery. However, these are generally modifications of well-known
      operative procedures. The sole genuinely new method is laparoscopy for which,
      however, no long-term results are available. An analysis of original articles
      shows that all surgical techniques for repair of the hernial orifice can be
      traced back to two simple repair principles: 1) reinforcement of the anterior
      wall of the inguinal canal and tightening of the external inguinal ring [Stromayr
      1559, Purmann 1692, Czerny 1877]. 2) reinforcement of the posterior wall of the
      inguinal canal and tightening the internal inguinal ring a) externally [Lucas
      Championniere 1881, Bassini 1889, Brenner 1898, Lotheissen 1898, McVay 1942,
      Shouldice 1945, Lichtenstein 1987, Stoppa 1989] or b) via an intra-abdominal
      approach (by laparotomy [Tait 1891] or laparoscopically [Ger 1990, Velez und
      Klein 1990]).

PMID- 8147154
TI  - [Incidence of peptic ulcers in patients with arterial occlusive diseases--a
      further risk factor?].
AB  - Acute bleeding of the upper gastrointestinal tract found in patients with
      arterial occlusive disease lead us to analyse the coincidence of arterial
      occlusive disease and pathological changes of the upper gastrointestinal tract.
      While waiting for reconstructive vascular surgery between 1986 and 1992 420
      patients underwent esophago-gastro-duodenoscopy for preoperative risk assessment.
      In 59% endoscopy revealed pathological findings in the upper gastrointestinal
      tract. Inflammation was found in 61.6% of the patients, in 15% gastric ulcer.
      Patients with gastrointestinal symptoms had no significant more pathological
      findings in gastroscopy (p = 0.1). We excluded 9.3% patients from primary
      elective vascular surgery because of their severe pathological findings. 19
      patients were operated on their gastrointestinal disease at first. In 7 patients
      we found an unknown carcinoma of the stomach. 5 patients got a resection of the
      stomach, in 2 patients an operation was unable. The diagnosis and therapy of risk
      factors are a major objective in the treatment of arterial occlusive disease. The
      results of the study stress the necessity of routinely performed endoscopy in
      patients awaiting vascular surgery. Beside a preoperative risk assessment this
      will lead to a lower incidence of serious gastrointestinal complications
      postoperatively.

PMID- 8147155
TI  - [The value of CEA immunoscintigraphy for diagnosis of colorectal cancer and its
      metastases: results of a prospective study].
AB  - The importance of the CEA-immunoscintigraphy (IS; BW 431/26 Fa Behring) for the
      diagnosis of colorectal carcinoma and its metastases was determined in a
      prospective trial including 60 patients. The results were compared with results
      of the ultrasound, the CT-Scan and the Angio-CT. Patients suffered from a
      colorectal carcinoma (15), from a local tumor recurrence after bowel resection
      (10), from hepatic (39) and/or extrahepatic metastases (16). In 40 patients the
      diagnosis was confirmed by laparotomy. Regarding the detection of hepatic
      metastases the sensitivity and specificity of the Angio-CT were superior to the
      IS (0.86 and 0.63 vs. 0.78 and 0.45). Ultrasound and Angio-CT together revealed
      true positive results in 89.2%. The IS did not improve this rate. Regarding the
      detection of extrahepatic metastases the sensitivity and the specificity of the
      CT were slightly superior to the IS (0.59 and 0.87 vs. 0.47 and 0.28). However,
      the IS increased the rate of true positive results by 18.8% (US + CT 43.7%; +IS
      62.5% true positive results). Due to these results the IS is not recommended as
      the method of choice to detect liver metastases. But in patients unfit for
      diagnostic laparotomy the IS may give additional information of the extrahepatic
      tumor stage.

PMID- 8147156
TI  - [Postoperative alkaline reflux after total gastrectomy for stomach cancer].
AB  - After presentation of postgastrectomy syndromes the methods for demonstrating the
      quantity of alkaline reflux are described. In 81 patients with gastrectomy the
      authors compare the reconstruction methods--named after Siewert/Peiper,
      Hunt/Lawrence, Schreiber and Schloffer--according to their reflux
      characteristics. The Y-Roux anastomosis shows better results than the Schloffer
      method.

PMID- 8147157
TI  - [High caloric parenteral nutrition in patients with mouth and oropharyngeal
      cancers--a clinical study].
AB  - Patients with carcinomas of the oral cavity and oropharynx often show signs of
      malnutrition. This is caused by reduced intake in patients due to chronic
      alcoholism resulting in suppressed appetite and disturbed gastrointestinal
      functions. Also the growth of the tumor can cause painful swallowing. The effects
      of chronic malnutrition reduce patients tolerance regarding surgical treatment,
      chemotherapy and radiation. A pretherapeutic parenteral balanced nutrition should
      achieve an anabolic metabolism. Changes in body cell mass (bcm) as a parameter of
      total protein synthesis can be estimated by bioelectrical impedance analysis in
      order to prove the success of this management. Twenty-eight patients participated
      in this study, divided into three groups: group 1 = 18 male subjects and group 3
      = 3 female subjects, all able to be operated upon, and group 2 = 7 male subjects,
      not able to be operated. High caloric nutrition in group 1 lead to a higher
      increase of bcm than in group 2. The review of single cases showed that in both
      groups one part of the patients failed increasing bcm despite nutrition. The
      therapeutic response was correlated to survival by means of a Kaplan-Meier
      analysis and a Cox-model. Survival probability could positively be correlated to
      an increased bcm.

PMID- 8147158
TI  - [Experience with surgical treatment of ruptures of the symphysis pubis].
AB  - Ten patients with symphyseal rupture and dehiscence of more than 10 mm who
      underwent different surgical procedures were reexamined between 8 and 59 months
      after surgery. In case of treatment within 3 weeks after the accident (n = 7)
      banding with completely absorbable Polydioxanon (PDS) cord (n = 4), PDS cord and
      crossing K-wires (n = 1), PDS-banding and plate-fixation for concomitant pubic
      fractures (n = 1), and wire banding (n = 1) were performed. In case of delayed
      operation (9 till 12 weeks after the injury n = 3) autologous bone grafts from
      the iliac crest were placed into the symphyseal split after removal of fibrous
      tissue, and double plate fixation (n = 2) respectively plate fixation and
      wirebanding (n = 1) were performed. There were no intraoperative and only 2 minor
      postoperative complications. The follow up revealed good and satisfactory results
      in 9 patients, and failure in one case. These results are better than to be
      expected from conservative management of this kind of injury. Banding with cord
      is a noteworthy alternative to wire banding and plate fixation.

PMID- 8147159
TI  - [Rational clinical examination of ligament ruptures of the upper ankle joint].
AB  - To eliminate drawbacks of the standard clinical examination technique of the
      ligamentous lesions of the ankle the author has developed his own method. The
      position of the patient is prone with bent knee. In evaluating the drawer sign
      manoeuvres rendering both, the full anterior shift of the foot and palpation of
      the talus, are used. During x-ray examination the same principles should be
      observed.

PMID- 8147160
TI  - [Initial experience with mycophenolate mofetil (RS 61443) after kidney
      transplantation].

PMID- 8147161
TI  - [Endometriosis of the inguinal ligament as a rare differential diagnosis of
      inguinal space-occupying lesion].
AB  - A case of endometriosis infiltrating the inguinal ligament is presented. As a
      rare condition involving of the extraperitoneal portion of the round ligament was
      not seen. Ultrasonography revealed a hypoechoic tumor with internal anechoic
      areas. Surgical exploration was carried out in the assumption of a relapse of an
      inguinal hernia. Microscopically, endometrial glands, fibrosis and old hemorrhage
      were seen. Laparoscopy revealed no evidence of pelvic endometriosis. We conclude
      that endometriosis must be considered in the differential diagnosis of palpable
      lesions of the groin in women of reproductive age. Surgery in cooperation with
      the gynecologist is the treatment of choice.

PMID- 8147162
TI  - [Electrolyte concentration, real and osmotic pressure in abscesses].
AB  - Electrolyte concentrations, osmotic and hydrostatic pressures of 26 abscesses in
      the head and neck area were measured. As the main cations Sodium (138 +/- 38
      mmol/l) and Potassium (37 +/- 16 mmol/l and as anions Chloride (183 +/- 46
      mmol/l) and Bicarbonate (10 +/- 4 mmol/l) were identified. The pH-value of the
      pus liquid decreased to 6.164 +/- 0.233. The calculated mean osmotic pressure of
      the pus liquid was 7910 +/- 1455 mm Hg whereas the measured physical pressure
      inside the abscess was 49 +/- 13 mm Hg. As a consequence of being an osmotically
      active system the inactivity of antibiotics in abscesses may be explained by a
      lack of diffusion through the abscess membrane, due to electrochemical charges or
      the size of the molecule, or by lack or reduction of the capillary perfusion and
      ultrafiltration rate due to physical pressure of the abscesses on perifocal blood
      vessels.

PMID- 8147163
TI  - [Possibilities of endoscopic diagnosis and therapy in reproduction medicine].
AB  - Endoscopic minimal invasive procedures have opened new horizons for preventive
      care and treatment in reproductive medicine. They provide best conditions for
      careful handling of tissues and preservation of organs. After exclusion of
      functional sterility factors, the basis of any further treatment is obtained by
      diagnostic pelviscopy, hysteroscopy and salpingoscopy, respectively falloposcopy,
      this even more for the endoscopic therapy of tubarian and uterine sterility
      factors as well as endometriosis. A large domain in the use of endoscopy is the
      organ and fertility preserving surgery in younger women. This applies mainly for
      the pelviscopic treatment of ectopic pregnancies and pelviscopic/hysteroscopic
      myomectomy. Despite of all controversial discussions pelviscopic ovarian surgery
      has many advantages for women who desire further pregnancies. Falloposcopy
      enlarges the possibilities for the diagnosis and treatment of ectopic
      pregnancies. More randomized studies are necessary in order to estimate the
      indications and advantages of endoscopic procedures. A wide and efficient use of
      these promising techniques requires an early and appropriate training of all
      gynecologic surgeons.

PMID- 8147164
TI  - [Fetal outcome after cervical ripeness-adjusted labor induction with
      prostaglandin E2 in relation to cervix status. Results of a multicenter study].
AB  - Prostaglandin E2 is often used for induction of labour. A procedure appropriate
      for obstetrical condition of the cervix uteri is recommended. 1,472 births with a
      medical indication were induced in a multicenter-study. With a bishopscore < 5
      prostaglandin E2 gel intracervical and with a score between 5 and 8 vaginal
      tablets were used for induction. Appropriate for the condition of cervix it was
      allowed to continue the induction. With a bishopscore > 8 an infusion of oxytocin
      was given. The fetal outcome was evaluated appropriate for the condition of
      cervix before and during induction of labour. The APGAR-score one minute post
      partum was < 8 in 10.8 per cent of all neonates. This part was near the same in
      the gel- and in the tablet group (p > 5%). By continuation of induction, the part
      with pathological findings was at all times not in relation to the different
      groups of cervical condition. It's the same by APGAR-scores 5 and 10 minutes
      after delivery. The acidotic morbidity at all was 10.7%. Also in this connection
      it was only an unimportant (p > 5%) increasing to observe then the induction was
      continued. There is no relation between the different groups of cervical
      condition and the acidotic morbidity. Under observation of mother and child the
      to cervical condition appropriated used method of induction of labour does not
      expect a bad neonatal outcome. The longer the cervix is unripen, the higher is
      the rate of delivery by caesarean section. The exploitation of the possibilities
      of induction by drugs can be recommended.

PMID- 8147165
TI  - [Results of radiotherapy of cervix cancer].
AB  - A total of 1,830 women with cervical carcinoma has been irradiated from 1959 to
      1986 with three different methods. 5 years survival rate was overall 44 per cent,
      in FIGO stage I 74 per cent, in stage II 55 per cent and in stage III 27 per
      cent. The better quality of life using high voltage technique is underlined.
      Including the paraaortic region into the radiation target volume may improve the
      results.

PMID- 8147166
TI  - [Vaginal acidity after tumor therapy].
AB  - We examined the vaginal acidity and vaginal status in 225 patients which were
      treated for a malignant tumor. We found the vaginal pH related to hormonal
      status, hormonal substitution, age and sexual activity. The vaginal pH could be
      reduced by estrogen-substitution, but local application of estriol has only a
      short effect. The determination of vaginal pH is a practically method to control
      the vaginal homoeostasis.

PMID- 8147167
TI  - [Peridural morphine administration for postoperative analgesia on the general
      medical unit].
AB  - With the present study the risk of postoperative peridural analgesia with
      morphine on ordinary wards should be estimated. 50 patients undergoing
      gynecological laparotomies received 3 mg morphine by a peridural catheter for
      postoperative pain relief. The degree of postoperative pain was objectivated by a
      visual analogue scoring system (1-10). Mean duration of analgesia was 11 hours.
      The pain score ranged between 1 and 3. The acceptance was very well. Heart rate
      and mean arterial pressure remained stable. Blood gas analyses showed a slight
      increase of the pCO2 with no clinical importance. The advantages of epidural
      morphine are: low dose, long duration, lack of sedation and the discharge of
      nurses. Experienced anesthesiologists visited all patients once a day. The nurses
      are educated to recognize complications.

PMID- 8147168
TI  - [Cortisol in amniotic fluid during PGE2-induced labor].
AB  - Concentrations of cortisol in amniotic fluid had been estimated during induced
      deliveries by prostaglandin E2 (group PG) and induced ones by oxytocin (control
      group OX). Cortisol concentration in amniotic fluid was much higher in group PG.
      The mode of action of prostaglandin on fetal lung had been analyzed. Our results
      prefer prostaglandin as drug of choice for induction of labour.

PMID- 8147169
TI  - Fetal macrosomia--pregnancy and delivery.
AB  - The authors have studied pregnancy, delivery and early neonatal status of
      macrosomic infants (> or = 4000 g) delivered between January 1, 1984, and
      December 31, 1992. The control group comprised age--and parity--matched pregnant
      women and their newborns weighing 3000 to 3999 g. From 9980 singleton
      pregnancies, 2021 (20.3%) macrosomics were delivered. The incidence of macrosomia
      was 16.7% in the primiparous group, 23.1% in the parity 2-4 group, and 28.2% in
      the multiparous group (parity > or = 5) (P < 0.001). The rates of macrosomic
      infants for pregnant adolescents (aged < or = 19 years), pregnant women aged 20
      34 years and old pregnant women (> or = 35 years) were 12.0%, 20.6% and 21.5%,
      respectively (P < 0.001). Macrosomia was not influenced by occupation and
      antenatal visits (P > 0.05). The rates of > or = 16 kg weight gain in the
      macrosomic and control groups were 36.2% (mean 14.30 +/- 4.66 kg) and 16.7% (mean
      12.18 +/- 4.82 kg), respectively (t = 12.05; P < 0.001). Of 546 pregnant women
      with fetal macrosomia subjected to oral GT testing, glucose intolerance was found
      in 20.0% and gestational diabetes in 4.8%. The rates of glucose intolerance and
      gestational diabetes in 259 control subjects were 13.9% and 2.3%, respectively (P
      < 0.05). Light (index 1-4) and moderate (index 5-7) forms of EPH gestosis were
      more common in the macrosomic group, whereas no difference was observed for
      severe forms (index > or = 8) between the groups (P > 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8147170
TI  - [Factor XIII deficiency as the cause of postoperative hemorrhage].
AB  - A 38-years-old woman is presented with recurrent postoperative bleedings. The
      coagulation analysis revealed a factor XIII deficiency. The treatment consisted
      in transfusions of factor XIII concentrates.

PMID- 8147171
TI  - [Ectopic pregnancy after laparoscopic tubal sterilization].

PMID- 8147172
TI  - [Delayed diagnosis of ovarian cancer with metastasis to the pancreas].
AB  - A report is given on a 72 years old woman with rare metastasis of ovarian cancer
      into the pancreas. Because of protracted diagnostic procedures of the pancreatic
      tumor the diagnosis has been neglected for 13 months. The tentative diagnosis
      "ovarian tumor" became important by ultrasonics 10 months after the appearance of
      the initial symptoms.

PMID- 8147173
TI  - Endoscopic creation of a neovagina using a segmented plexiglass mould--case
      report.

PMID- 8147174
TI  - [Thermal preparation techniques in gynecologic endoscopy--technical, experimental
      and clinical results (n=2000)].
AB  - A comparative study on thermal, mainly laser and high frequency electrosurgical
      techniques, was conducted. Indications, handling and morphometric results were
      correlated. Morphometrical findings suggest that minimal thermal tissue damage is
      associated by a decrease in the hemostatic effect. Additional bipolar coagulation
      is necessary when using the carbon dioxide laser or high frequency electrodes. As
      thermal tissue lesion is concerned, the two techniques differ only slightly, by
      fractions of millimeters. Concerning clinical handling and practicability at our
      department, as well as in the centers participating at the European Consensus
      Study on Lasers in Gynaecology, high frequency electrosurgery has proven the
      method of choice for endoscopic ablative procedures. The carbon dioxide laser (at
      laparoscopy) and the Nd:YAG contact laser (at hysteroscopy) are preferentially
      employed for reconstructive surgery (e.g. the carbon dioxide laser for treatment
      of distal tubal pathology or endometriosis, the Nd:YAG contact laser for
      hysteroscopic synechiolysis).

PMID- 8147175
TI  - [Evaluation of climacteric symptoms (Menopause Rating Scale)].
AB  - Quantification and qualification of climacteric symptoms had been described by
      Kupperman et al in 1953. New findings and ideas in the following forty years
      needed a correction of Kupperman index. Two important groups reduced the
      essential symptoms only on two ones, vasomotoric hot flushes and genital atrophy.
      On the contrary, Menopause Rating Scale (MRS) presented here enables registration
      of so called psychic symptoms, too, essential for quality of life. Complaint from
      bladder and urethra, hints and muscles and sexual disorders are also registered.
      For each of the ten symptom groups there is a rating scale from 0.0 (no symptoms)
      to 1.0 (very strong symptoms), in a graphic, too. In this way an individual
      profile will be visible. Using MRC it is possible, to quantify a better or worst
      status during and after treatment and to depict it.

PMID- 8147176
TI  - [Hysteroscopy versus hysterosalpingography in diagnosis of sterility and
      infertility].
AB  - In a prospective study of 68 infertile patients the findings of
      hysterosalpingography and hysteroscopy have been compared. Hysterosalpingography
      showed in 3 cases false-negative results and in 10 cases false-positive results.
      Hysterosalpingography is especially limited for diagnostics of intrauterine
      adhesions. Hysteroscopy should be a necessary component of diagnostics of
      sterility, also in case of normal hysterosalpingographical findings.

PMID- 8147177
TI  - [Fetal enlarged flaccid intestinal loops and pathologic Doppler findings-
      criteria for fetal distress].
AB  - In pregnancies with signs of placental insufficiency relatively often flaccid and
      enlarged intestinal convolutions were detected, which differed markedly from
      hyperperistaltically distended convolutions as in the case of bowel obstructions.
      In order to show a correlation between placental insufficiency i.e. a deficiency
      in supply--and the typical flaccid bowels, we performed a prospective study on
      258 pregnant women with placental insufficiency and a control group of 151 normal
      pregnancies. The examinations were performed with a color duplex system. As
      criterium we registered detection of flaccid bowel convolutions-characterized by
      rich echoes-which could be well distinguished from the bowel which appears as
      homogeneous. It could also be well differentiated from the mostly echo-free
      aspect of obstructed bowels, associated by hyperperistaltics. Flaccid and
      enlarged bowel convolutions were found in 67 patients in the collective with
      placental insufficiency (26%) and in 8 patients in the control group (5%). In all
      fetuses the aorta as well as the carotic artery were examined by Doppler
      sonography. In the group with placental insufficiency markedly increased values
      were noted from the resistance index (RI) in the aorta as compared to the
      controls. The values in the carotis, however, were lower. This must be considered
      as a sign for a higher degree of centralization in these fetuses with supply
      deficiency. In those fetuses with enlarged bowel convolutions the doppler
      parameters were even more pathologic. Their post partal condition was also
      clearly worse. In 28 fetuses of this group in almost all cases no diastolic flow
      could be detected in the arteria mesenterica superior, whereas such a flow was
      found in all other cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147178
TI  - Common intrapartum denominators of shoulder dystocia related birth injuries.
AB  - The intrapartum background of fetal injuries associated with shoulder dystocia
      was studied retrospectively on the basis of 107 relevant medical records.
      Intrapartum use of oxytocin and protraction-arrest disorders, the latter
      particularly during the second stage of labor, were frequent findings. Delivery
      was effected by forceps or vacuum extraction in almost one-half of the cases.
      Shoulder dystocia related permanent fetal impairments were closely connected to
      macrosomia. The fetal weight was > or = 4,000 grams in about 75% and > or = 4,500
      grams in approximately 40% of the instances. Permanent hypoxic or traumatic
      cerebral damage was documented in almost one-third of the cases. The data
      indicate that in connection with coincidental neonatal afflictions, the birth
      weights of the fetuses are higher and instrumental extractions are more frequent
      than in relation to all clinically diagnosed cases of shoulder dystocia.

PMID- 8147179
TI  - [Analysis of 122 twin deliveries with special reference to morbidity and
      mortality of the second twin].
AB  - 122 consecutive twin deliveries between 1986-1992 were analysed retrospectively
      under special consideration of morbidity and mortality of the second twin. 13.9%
      of the twin deliveries occurred before the 33rd week of gestation. The cesarean
      section rate amounted to 49.2%, the first twin was delivered in 5.7%, the second
      twin in 27%, by vaginal operative methods. Perinatal mortality of the first twin
      was 3.3%, of the second twin 6.6% (p < 0.01); thus resulting in an overall twin
      mortality rate of 4.9%. The acidosis-rate of 16.4% in the second twin was
      significantly above the 9.0% in the first twin. The vaginal operative mode
      delivery especially contributed to the impaired outcome of the second twin. There
      was no correlation between the morbidity of the second twin and the time interval
      between the two deliveries.

PMID- 8147181
TI  - [Puerperal uterine inversion (report of 3 cases)].
AB  - The Inversio uteri puerperalis belongs to the obstetrical emergencies. Immediate
      reposition, treatment of shock and the use of beta-mimetics can reduce morbidity
      and mortality. Surgery for reposition should be used if manual reposition failed.

PMID- 8147180
TI  - [Postmenopausal hemorrhage and endometrial cancer in tamoxifen therapy].
AB  - Report about 8 patients with endometrial pathology during tamoxifen therapy: 1
      endometrial cancer, 1 adenomyosis uteri and 6 endometrial polyps. The knowledge
      about effects of tamoxifen on endometrium and possibilities of prevention are
      discussed. Sonographic screening of patients during tamoxifen therapy and if need
      by endometrial biopsy is necessary especially if tamoxifen is given longer than 2
      years. No more than 30 mg should given in adjuvant therapy.

PMID- 8147182
TI  - [Fibromatosis of the breast--a case report and review of the literature].
AB  - A case of fibromatosis of the breast mimics a carcinoma by its clinical and
      mammographic features. The morphological image of this rare disease of the breast
      is described. The fibromatosis of the breast has to be distinguished
      histologically from a fibroma and from a low-grade fibrosarcoma. The dignity of
      the lesion is confirmed by histological and immunohistochemical examination. The
      possibilities of therapy are discussed and compared with data of the literature.

PMID- 8147183
TI  - [What advantages does treatment with highly purified FSH have in infertility?].

PMID- 8147184
TI  - [Coital anorgasmia in marriage].
AB  - Out of a sample of 2,425 gynecological patients aged 21-40 and married for at
      least one year, three groups were selected according to the frequency of coital
      orgasm. The first group contained 1,266 (52.2%) orgastic women, the second group
      included 172 (7.1%) patients who did not reach orgasm during coitus, and the
      third group consisted of 55 (2.3%) patients whose absent orgasms were felt by the
      examinees as distressing. Significant differences were found between the three
      groups concerning family environment and childhood, level of education and
      professional standing, sexual development and life, and in the incidence of
      psychopathological symptoms. It appears that the absent capacity of women to
      attain orgasm in sexual intercourse is caused by several factors of both
      biological and psychosocial nature.

PMID- 8147185
TI  - [Sperm antibodies--a suitable parameter for diagnosis of fertility?].
AB  - Antibodies against spermatozoa specific antigens may be produced in female as
      well in male subjects. There is some evidence that they are able to contribute to
      infertility in susceptible couples. Therefore, we studied these antibodies with
      regard to the diagnostics of infertility. It is shown that there is no
      significant enhancement in the serum levels of the antibodies in infertile female
      patients and their partners. The figures measured are comparable to those found
      in pregnant or in climacteric women. It is concluded that the determination of
      these antibodies does not contribute to an improved diagnostic of infertility.

PMID- 8147186
TI  - [Is determination of C-reactive protein and haptoglobin in puerperium suitable
      for further therapeutic decisions?].
AB  - A report is given on the levels of c-reactive protein (crp) and haptoglobin (hpt)
      of 168 puerperae at the second and fourth day post partum. All of the patients
      had a afebrile puerperium. We conclude that the value of crp (< 5 mg/l) is grown
      up during the puerperium. That ist why the sole analysis of crp is not to be a
      criteria for decision during the puerperium.

PMID- 8147187
TI  - [Combination of Cantrell pentalogy and amniotic band syndrome: a case report].
AB  - A case is reported of sonographic diagnosis of ADAM-complex (amniotic band
      syndrome) in combination with Cantrell-syndrome in the 19th gestational week. The
      ultrasonic investigation also showed a large defect in the fetal skull with
      encepholocele as well as a marked defect of the abdominal wall and chest with
      dislocation of the intestines, liver, and heart. The pregnancy was interrupted
      because of the severe fetal malformations. Aetiology and pathogenesis of such
      rare abnormalities and possible correlations between ADAM-syndrome and Cantrell
      syndrome are discussed with reference to the literature.

PMID- 8147188
TI  - [Mature tubal pregnancy with healthy child and mother--a case report].

PMID- 8147189
TI  - Etiology and pathophysiology of preeclampsia.
AB  - The possible involvement of genetic and immune mechanisms in the etiology of
      preeclampsia has attracted increasing attention. Preeclampsia is characterized by
      a generalized disturbance in endothelial physiology, and not merely by an
      isolated defect in vascular prostacyclin synthesis. The increased production of
      oxygen free radicals and/or elastase by activated lymphoid cells in the pregnant
      decidua, a mainly lymphoid tissue, may be the link between the hypothetical
      immunologic mechanisms and the endothelial injury occurring in preeclampsia.

PMID- 8147190
TI  - [The new terminology and classification of hypertensive diseases in pregnancy].
AB  - For hypertensive disorders of pregnancy there are not only a lot of terms and
      trials for classification--but also the definition of hypertension as the leading
      sign is unclear. This explains the confusion around this meaning-full problem.
      The International Society for the Study of hypertension in Pregnancy (ISSHP)
      submitted proposals for a new terminology and classification of hypertensive
      disorders in pregnancy. The members of the ISSHP's German Section and the German
      Study group for Hypertension in Pregnancy/Gestosis simplified this new ISSHP
      proposal and adapted it to the peculiarities of German language. This new concept
      is presented and recommended for use in medical practice.

PMID- 8147191
TI  - [Hypertensive complications in pregnancy--a special evaluation of the Rhineland
      Pfalz perinatal study].
AB  - In a special analysis of the perinatal database Rheinl.-Pfalz of the years 1989
      and 1990 1,876 pregnancies with the risk-factor "gestosis" (2.4% of all
      deliveries) were evaluated. In comparison to all deliveries (n = 78,250)
      significantly different incident-rates could be observed: Sterility, working
      during pregnancy, nationality, parity, psycho-social stress, multiples,
      adipositas, diabetes mellitus, pathological increase of body weight, urinary
      infection, number and duration of antenatal hospitalisation. Prematurity and
      fetal retardation as well as placental insufficiency, pathological antenatal CTG,
      green amniotic fluid and intrapartel acidosis was seen much more often in the
      risk group, resulting in a much higher rate of caesarean section (50.1 versus
      13.7%) and an increased maternal and fetal morbidity. Perinatal mortality was
      twice as high in the risk group compared to the control. Thought data quality is
      limited in this study covering a very larger area, the results underline the
      unchanged importance of hypertensive disorders in perinatology.

PMID- 8147192
TI  - [Different forms of hypertension in pregnancy: pediatric and maternal risks].
AB  - Incidence of hypertension in pregnancy is 5 per cent. Half of these 372 cases are
      gestational hypertensives. 24.4 per cent of the patients had preeclampsia and
      20.2 per cent had chronic hypertension, 6 per cent of the patients with
      hypertension in pregnancy had a coincidental chronic kidney disorder. Only
      pregnant patients with preeclampsia are risk patients with respect to maternal
      health as well as to fetal risk.

PMID- 8147193
TI  - [Incidence of hypertension in pregnancy in relation to the definition of
      hypertension].
AB  - According to a proposal of the International Society for the Study of
      Hypertension in Pregnancy (ISSHP) the definition of hypertension is based on a
      diastolic blood pressure of 90 mmHg or more. Systolic and mean arterial blood
      pressure (e.g. MAP II) are not be taken into account. Out of a clear defined
      district the totality of n = 2259 pregnant women has been strictly supervised
      till to delivery and afterwards. The frequency of hypertension according to the
      old ACOG-definition was calculated to be 15.9% (n = 360). According to the newer
      ISSHP-definition it was 12.7% (n = 287). To detect severe and hazardous cases the
      newer ISSHP-definition seems to be better than the older definition of ACOG.
      Therefore, the acceptance of the ISSHP-proposal is recommended.

PMID- 8147194
TI  - [Pre-eclampsia versus essential hypertension--the course of pregnancy, labor and
      fetal outcome].
AB  - By means of an exact nephrologic examination 6 weeks post partum of 128 patients
      with hypertension in pregnancy an exact classification in preeclampsia (46 per
      cent), chronic hypertension (34%) and superimposed preeclampsia (13 per cent) is
      possible. In cases of essential hypertension a hypotensive therapy is necessary.

PMID- 8147195
TI  - [Mortality and prognosis of premature infants of very low birth weight (500-1,500
      g) in relation to degree of maturity].
AB  - In a retrospective study we analysed the influence of intrauterine growth
      retardation on mortality and early prognosis of 136 liveborn singletons of very
      low birthweight (VLBW) born between 1986 to 1992 at the Department of Obstetrics
      and Gynecology of the University Hospital of Cologne. The main causes of
      premature delivery in the appropriate-for-gestational-age (AGA)-group were
      premature rupture of membranes with an incidence of 73% and in the small-for
      gestational-age (SGA)-group the pregnancy induced hypertension with an incidence
      of 44%. With a similar mean birth weight (1,009 g vs. 1,115 g) the SGA-prematures
      showed a three weeks higher mean gestational age (31.3 vs. 28.3 weeks). The
      mortality was 10% higher in the AGA-group than in the SGA-group (30% vs 20%); as
      regards the whole study group the mortality showed an inverse correlation to
      birthweight. In the age between 11 months and 6 years severe handicaps and
      developmental retardations were found more often within the previous AGA
      prematures with an incidence of 23% (6/26) than within the previous SGA
      prematures with an incidence of 11% (4/36); the incidence and severeness of later
      handicap were not dependent on birthweight. Accordingly to our results mortality
      and early prognosis of VLBW-prematures seem to be dependent on gestational age;
      whereas the mortality showed an inverse correlation to birthweight, the early
      prognosis did not.

PMID- 8147196
TI  - [Doppler ultrasound perfusion measurements of uterine, fetal and fetoplacental
      vessels in pregnancies with ultrasonically suspected fetal growth retardation].
AB  - The aim of the present study was determination of the complex character of
      hemodynamic disturbances in uteroplacental, fetoplacental and fetal vessels as
      well as their influence on the outcome of pregnancies suspected to have IUGR on
      ultrasound examination. A special form of Doppler scoring was implemented for
      documentation of the hemodynamic disturbances. Of 82 single pregnancies with
      sonographically suspected IUGR, 30 women gave birth to eutrophic babies whereas
      52 mothers delivered hypotrophic newborns. However, 43 cases of the hypotrophic
      babies had birth weight below the 5th percentile. The median values of Doppler
      indices for those with eutrophic babies revealed no significant differences
      compared to normal collective. However, significantly elevated RI and PI values
      in both uterine arteries, the umbilical artery and fetal descending aorta of
      pregnancies which resulted in hypotrophic babies indicated hemodynamic
      disturbance. The umbilicoplacental and uteroplacental vasculature compartments
      were almost equal involved with a proportion of 39% or 30% respectively. Birth
      weight < or = 5th percentile was associated with a further increase of
      pathological values in this both vascular areas. Significant rang correlations
      between values of Doppler indices and clinical parameters indicated a direct
      association between perfusion disturbances and fetal outcome of the pregnancies
      studied. The present Doppler score, which is a summary of all separately
      evaluated examined blood vessels, is suitable for clinical implementation and
      showed a good correlation to the clinical parameters in our study. Therefore
      Doppler perfusion measurements should play an important role in the clarification
      of suspected fetal growth retardation.

PMID- 8147197
TI  - [Significance and consequences of mild fetal kidney pelvis dilatation].
AB  - Even mild fetal pyelectasia is a subject to post-partal control. As fetal kidneys
      can easily be examined by ultrasound, different degrees of dilatation are found,
      but the discrimination between normal and pathological has not yet been defined.
      We considered any dilatation of less than 7 mm als normal. 52 fetuses were found
      to have a dilatation of 7 mm and more. 8 of them required post partum surgery:
      2/15 classified as Grignon grade I, 3/14 as Grignon II, and 3/3 as Grignon III.
      Further malformations in addition to pyelectasia require a prenatal caryotyping
      procedure.

PMID- 8147199
TI  - Bibliographic index, 1988-1992.

PMID- 8147198
TI  - [Labor stress and postpartum neonatal weight development].
AB  - 55 years ago the term "stress" was defined as a general reaction pattern which,
      in moderation, is not only unharmful but even has a vital function. Does this
      also apply to intrapartal fetal stress? The results from a retrospective pilot
      study including 791 mature newborns without major disorders are presented to
      stimulate discussion and possibly give rise to prospective studies. 1. Newborns
      from primigravidas with labour spanning more than 12 hours incurred postpartal
      weight loss in excess of 5% of their birthweight only half as often as infants
      with shorter delivery periods. In other words, a longer expulsion phase tended to
      be correlated with lower postpartal weight loss in neonates. 2. As expected, the
      1-minute-Apgar score was no statistically valid predictive parameter for the
      adaptation phase in the first 5 postpartal days of newborns. Infants with 1
      minute Apgar scores of up to 6 had reached their birth-weight on the 5th
      postpartal day rather more often than those with better 1-minute Apgar scores. 3.
      In the group of mature newborns involving premature rupture of the membranes a
      marked gain on birthweight up to the 5th postpartal day was seen only half as
      often as in the group with rupture of membranes at term. 4. Weight loss of only
      slight proportions was seen in newborns admitted to the pediatric hospital
      because of suspected intra-amniotic infection half as often, compared to the
      other infants who also reached their birthweight faster than those with suspected
      intra-amniotic infection. 5. Oxytocin administered to aid labour had a positive
      effect on postpartal weight development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147200
TI  - Subclassification of benign breast disease by fine needle aspiration cytology.
      Comparison of cytologic and histologic findings in 265 palpable breast masses.
AB  - The cytologic and histologic features of 265 benign breast masses were analyzed
      in order to examine the ability of fine needle aspiration cytology to accurately
      subclassify benign breast lesions. Two hundred two of the masses were pure
      histologic examples of benign breast lesions (72 nonproliferative fibrocystic
      change, 27 proliferative fibrocystic change, 65 fibroadenoma, 12 abscess, 8 fat
      necrosis, 7 papilloma, 7 duct ectasia, 2 tubular adenoma, 1 sclerosing adenosis,
      1 microglandular adenosis), and 63 masses were mixed lesions. Part I of the study
      consisted of retrospective comparison of the original cytologic diagnoses with
      the histologic diagnoses. A nonspecific descriptive diagnosis had been rendered
      in 135 of 265 (51%) cases, and these descriptive diagnoses corresponded to
      fibrocystic change in the majority of cases (70%). A specific benign cytologic
      diagnosis had been made in 130 of 265 (49%) cases, and overall the specific
      diagnosis was correct in 80% of cases. Part II of the study consisted of the
      semiquantitative scoring of the cytologic findings of the 202 pure examples of
      benign breast masses and statistical analysis of differences in the expression of
      cytologic features between the different types of lesions. Overall cellularity,
      amount of bipolar stripped nuclei, amount and architectural arrangement of
      epithelium, epithelial atypia/pleomorphism/nuclear overlapping and amount of
      apocrine metaplasia, foam cells and stroma were the cytologic parameters that
      were statistically significant (P < .05) in distinguishing between the cases of
      fibroadenoma, abscess, papilloma, fat necrosis, duct ectasia and fibrocystic
      change as a group. No cytologic parameter reached statistical significance in
      distinguishing between proliferative and nonproliferative fibrocystic change. We
      conclude that the majority of benign breast lesions yield characteristic
      cytologic findings that allow their subclassification when sufficiently sampled
      by fine needle aspiration. The distinction between proliferative and
      nonproliferative fibrocystic change is less reliable, and cytologic differences
      observed within this spectrum did not reach statistical significance.

PMID- 8147201
TI  - Fine needle aspiration cytologic diagnosis of axillary accessory breast tissue,
      including its physiologic changes and pathologic lesions.
AB  - Sixty-nine cases of axillary accessory breast tissue, including its physiologic
      changes and pathologic lesions, were diagnosed by fine needle aspiration
      cytology. The age of the patients ranged from 13 to 40 years, with a median of
      25, and all were female. The cases presented with swellings in the left axilla in
      16 cases, right axilla in 30 cases and both axillae in 23 cases. The common
      clinical diagnoses included accessory breast tissue (23.2%), lipomatous lesion
      (17.4%), lymphadenopathy (18.8%) and swellings not otherwise specified (30.4%).
      In 8.8% cases two of the possibilities were considered. The cytodiagnoses
      included axillary accessory breast tissue (47 cases), axillary breast tissue with
      pregnancy or lactational changes (15), cystic disease (4) and fibroadenoma (3).
      One of the cystic disease cases showed granulomatous inflammation. Although no
      case of carcinoma in axillary breast tissue was diagnosed during the study
      period, there were two cases of malignancy in axillary swellings (diagnosed as
      metastatic carcinoma) when no primary was detected in the breasts.

PMID- 8147202
TI  - Fine needle aspiration cytology of breast ductal carcinoma in situ.
AB  - To evaluate the role of fine needle aspiration cytology (FNAC) in identifying in
      situ breast carcinoma, we reviewed 19 FNACs of histologically confirmed pure or
      predominantly ductal carcinoma in situ (DCIS). The cytologic diagnosis was
      positive for malignancy in 53%, suspicious in 31% and nondiagnostic in 16%. An
      intraductal lesion was suggested prospectively in 21%. Retrospective review
      showed three distinctive cytologic criteria in cases with DCIS: (1) cohesive
      groups of atypical ductal cells associated with scattered, individual malignant
      cells or a necrotic background; (2) hyperplastic ductal cells with associated
      malignant cells or necrosis; and (3) true tissue fragments composed of cohesive
      epithelial cells with a cribriform pattern. One or more findings were present in
      81% of the malignant or suspicious FNACs; 19% could not be distinguished
      cytologically from invasive carcinoma. We studied a control group of 30 invasive
      ductal carcinomas; one or more criteria were found in 35% of cases with no or a
      minor DCIS component but in 73% of those with an extensive DCIS component. We
      conclude that these three criteria deserve further study as an aid in suggesting
      DCIS on FNAC.

PMID- 8147203
TI  - Value of ancillary studies in fine needle aspiration cytology of the lung.
AB  - The importance of ancillary studies in surgical pathology of the lung is well
      documented. Less well established is the utility of these methods in fine needle
      aspiration (FNA) cytology of the lung. We reviewed our experience over a two-year
      period (1990-1991) with the use of ancillary studies in addition to routine light
      microscopy in FNA of the lung. Three hundred forty-five percutaneous aspirations
      were performed under radiologic guidance during this period. A diagnosis of
      malignancy was made in 233 (68%) cases. Thirty-two aspirates provided specific
      benign inflammatory or infectious diagnoses of mass lesions. Approximately one
      half the cases required no additional studies (181/345, 52%). Immunocytochemistry
      was performed in 50 cases (14.5%), electron microscopy (EM) in 28 cases (8%),
      microbiologic staining in 42 cases (12%), mucin staining in 72 cases (21%) and
      cell blocks in 77 cases (22%). Immunocytochemistry and EM were generally used to
      classify poorly differentiated neoplasms, confirm the diagnosis of
      bronchioloalveolar cell carcinoma, determine neuroendocrine differentiation and
      establish primary sites for suspected metastatic malignancies.
      Immunocytochemistry provided significant additional information in 20 (40%) of
      the cases in which it was attempted and confirmed the light microscopic
      impression in an additional 18 cases (36%). Similarly, EM provided significant
      additional information in 10 cases (67%) and confirmed the light microscopic
      impression in an additional 4 cases (27%). Microbiologic staining was performed
      when an infectious etiology was suspected clinically or an inflammatory
      (especially granulomatous) background was present in the smears. In 11 cases
      (27%) the staining was positive for organisms. Mucin staining was performed in an
      attempt to better classify poorly differentiated non-small cell malignancies and
      was contributory in 68% of the cases. In conclusion, ancillary studies are
      helpful in confirming the cytologic impression and making a more specific
      diagnosis in FNA of the lung.

PMID- 8147204
TI  - Cytodiagnostic clues to primary retinoblastoma based on cytologic and histologic
      correlates of 39 enucleated eyes.
AB  - In 39 cases undergoing ocular enucleation, cytologic characteristics of primary
      intraocular retinoblastomas were examined in relation to histologic findings.
      Retinoblastoma cells occurred singly or in clusters within the associated
      necrotic debris. Calcific deposits were present in both cytologic and histologic
      specimens. Portions of capillaries with perivascular tumor infiltrates were
      identified as pseudorosettes. Wright rosettes were occasionally seen in poorly
      differentiated retinoblastomas. Flexner-Wintersteiner rosettes were uncommon;
      however, "mirror ball-like" clusters in cytologic materials correlated well with
      the rosettes and were a diagnostic clue. Cytomorphologically, the tumor cells
      could be divided into two types that reflected their histologic grading of
      differentiation. These findings are cytodiagnostic clues to the presence of
      retinoblastomas and can be helpful in the cytologic diagnosis.

PMID- 8147205
TI  - Orbital lesions. Diagnosis by fine needle aspiration cytology.
AB  - Over seven years (1983-1989), 30 orbital lesions were subjected to fine needle
      aspiration (FNA). The age of the patients ranged from 1.5 to 65 years. The
      male:female ratio was 16:14. The presenting features were proptosis (15 cases),
      swelling of eyelids (6), swelling of medial or lateral canthus (6), swelling of
      infraorbital margin (2) and recurrent orbital mass in a surgically treated case
      of retinoblastoma (1). FNA was performed on intraocular sites in 2 cases, orbital
      cavity in 11 and adnexal swellings in 17. The cytodiagnoses were various
      inflammatory lesions (5 cases), benign cystic lesions (4), meibomian gland
      carcinoma (3), retinoblastoma (3), meningioma (2) and pleomorphic adenoma (2).
      Basal cell carcinoma, mucoepidermoid carcinoma, undifferentiated carcinoma, optic
      nerve glioma, acute myeloid leukemia, leiomyosarcoma and neurofibroma accounted
      for 1 case each. In 4 cases the cytologic specimens were inadequate.

PMID- 8147206
TI  - Fine needle aspiration findings in generalized post-Calmette-Guerin bacillus
      lymphadenitis presenting as an abdominal mass.
AB  - Generalized lymphadenopathy with an abdominal mass following a Calmette-Guerin
      bacillus vaccination is a rare complication and often confused clinically with
      malignant neoplasms, such as lymphoma and leukemia. Smears from lymph nodes and
      abdominal masses reveal numerous macrophages with streaked or wrinkled cytoplasm.
      These cells closely resemble Gaucher cells. The streaked appearance of the
      cytoplasm is due to the presence of numerous acid-fast bacilli in the cytoplasm.

PMID- 8147207
TI  - Utility of gastric brushing in the diagnosis of malignant lymphoma.
AB  - The gastric brushings (GBRs) and endoscopic biopsies obtained concurrently from
      27 patients in whom malignant lymphoma was diagnosed or suggested by either
      modality were assessed to evaluate the utility of cytologic examination in the
      diagnosis of gastric lymphoma. GBRs provided a definitive diagnosis of lymphoma
      in 2 (28%) of 7 patients with a prior history of lymphoma and 10 (56%) of 18
      patients with primary gastric lymphoma, yielding an overall sensitivity of 48%.
      All the lymphomas diagnosed cytologically were large cell type. GBRs were
      suspicious for a malignant neoplasm in four lymphoma patients whose concurrent
      biopsies were negative. GBRs obtained from two patients who had gastritis were
      reported as suspicious for lymphoma. There were no false-positive diagnoses.

PMID- 8147208
TI  - Hepatoblastoma. An attempt to apply histologic classification to aspirates
      obtained by fine needle aspiration cytology.
AB  - We applied cytologic and architectural diagnostic criteria to the aspiration
      smears of six cases of hepatoblastoma (HBL) in order to establish whether it is
      possible to obtain a reliable cytologic diagnosis of this neoplasm and to
      subclassify it based on cytologic evidence alone. We describe two groups of HBL,
      undifferentiated and differentiated. The undifferentiated group comprises
      anaplastic and embryonal subtypes, and the differentiated group comprises fetal
      and macrotrabecular subtypes. Our findings suggest that the fetal and
      macrotrabecular subtypes have a rather characteristic cytologic pattern,
      permitting us to differentiate between the two and to distinguish them from the
      other two subtypes. The differential diagnosis between the anaplastic and
      embryonal subtypes is more complex and can be difficult to carry out using
      cytologic criteria exclusively. The immunophenotypic pattern reflects the degree
      of maturity of each subtype and helps with cytologic subclassification. The
      cytologic differential diagnosis of undifferentiated HBL must include hepatic
      metastases of small round cell tumors of childhood. The cytologic differential
      diagnosis between differentiated HBL and hepatocellular carcinoma may be very
      difficult. We suggest that the cytologic subclassification of HBL is possible
      with the reservation that the predominant pattern may mask other, associated
      patterns.

PMID- 8147209
TI  - Esophageal cytology and subsequent risk of esophageal cancer. A prospective
      follow-up study from Linxian, China.
AB  - This paper reports a 15-year follow-up study of 12,693 persons in Linxian, China,
      who were originally screened by esophageal balloon cytology in 1974. The purpose
      of the study was to evaluate the ability of esophageal balloon cytology to
      identify individuals at increased risk for developing esophageal cancer. Age, sex
      and cytologic diagnoses were obtained from the original 1974 records, and
      information on vital status, cancer experience and potential confounding risk
      factors was collected from interviews and medical abstracts in 1989. A total of
      1,162 incident cases of esophageal cancer and 993 deaths due to esophageal cancer
      were identified and used in this analysis. The follow-up study showed that the
      risk of esophageal cancer incidence and mortality increased in parallel with the
      presumed severity of the 1974 Chinese cytologic diagnoses. After adjusting for
      potential confounding factors, the relative risks (and 95% confidence intervals)
      for esophageal cancer incidence, by cytologic diagnosis, were: normal, 1.00;
      esophagitis, 1.52 (1.07-2.14); hyperplasia, 1.17 (1.02-1.33); dysplasia 1, 1.53
      (1.10-2.14); dysplasia 2, 1.89 (1.47-2.41); and suspicious for cancer, 5.77 (3.79
      8.80). These results suggest that esophageal balloon cytology, as performed and
      interpreted in Linxian in 1974, successfully identified individuals at increased
      risk for esophageal cancer.

PMID- 8147210
TI  - Clinical significance of an inconclusive cytopathologic diagnosis. I. Positive
      predictive value.
AB  - We retrospectively analyzed the pathology database of 1,057 patients at Duke
      University Medical Center who received an inconclusive cytopathologic diagnosis
      during the five-year period 1984-1989 in an attempt to answer the question, what
      is the significance of a cytopathologic diagnosis of "atypical cells are present
      that are suspicious for, but not diagnostic of, malignancy?" We identified 1,110
      cytologic specimens from all body sites receiving this diagnosis, and of them,
      805 (73%) had a follow-up specimen from the same anatomic site that was
      definitive as to the presence or absence of malignancy; 305 (27%) had no follow
      up specimen. Of the follow-up specimens, 596 (74%) were histopathologic
      specimens, and 209 (26%) were cytopathologic. Specimens from the respiratory
      tract accounted for 51% (563) of the cases, and the positive predictive value
      (PPV) of an inconclusive diagnosis at this site was 85%. Of the remaining
      specimens, those from the urinary (10%) and genital (8%) tracts were the most
      common, and the PPVs of an inconclusive diagnosis at these sites were 83% and
      61%, respectively. The overall PPV of an inconclusive cytologic diagnosis from
      all body sites was 80% and ranged between 57% and 93%, depending on the anatomic
      site.

PMID- 8147211
TI  - DNA ploidy of ovarian and adnexal cyst fluid. A useful adjunct to cytology.
AB  - It is increasingly common for cytology laboratories to receive ovarian, adnexal
      and pelvic cyst fluids obtained via sonographically directed aspiration and
      laparoscopic techniques, especially from women who are desirous of preserving
      fertility or who are undergoing in vitro fertilization (IVF). Accurate
      characterization of such cysts is a worthwhile goal, given the superior prognosis
      for ovarian carcinomas that are diagnosed at an early stage. In an effort to
      improve upon the false-negative diagnosis rate associated with cytology, we
      evaluated DNA ploidy as a possible adjunctive criterion. We examined 55 benign, 3
      borderline and 6 malignant aspirates received by our cytopathology laboratory; 35
      were aspirated directly from the patient from clinically and ultrasonographically
      benign cysts, and 29 were aspirated from surgically removed benign (20) and
      malignant (9) cysts. Adjunctive DNA ploidy and cell cycle analysis was performed
      using the Cell Analysis Systems CAS-200 on Feulgen-stained cytologic smears of
      the 64 cyst fluids. Adequate material for DNA analysis was obtained from 33/35 in
      situ aspirated cysts and from 19/29 surgical specimen cysts. Forty-seven of 52
      cytologically benign cysts were diploid. Of the 5 nondiploid benign cysts, 3 were
      follicle cysts (2 from hormonally stimulated IVF patients and 1 from a postpartum
      patient), and 1 was a benign cystic teratoma. Their nondiploid DNA pattern or
      tetraploidy may be due to a high proliferative index. The fifth nondiploid benign
      aspirate was from a resected benign epithelium-lined cyst; its DNA histogram
      contained a conspicuous tetraploid population. All 9 malignant cysts were
      cytologically malignant. Of the 3 borderline cysts, 1 was nondiploid, and 2 were
      diploid. All 6 fully malignant cysts were nondiploid; 2 of them were tetraploid.
      Based on our results, we conclude that DNA ploidy analysis of cells derived from
      ovarian and adnexal cyst aspirates is feasible (in 95% of cases) and relatively
      specific (90%) and has a relatively high negative predictive value (92%). The
      results are not sufficiently predictive of the histology of the lesion to warrant
      therapeutic intervention based on ploidy alone (sensitivity of nondiploid
      results, 78%; positive predictive value of nondiploid results, 58%). Nondiploidy
      should suggest consideration, but is not conclusive, of a malignancy diagnosis.
      There may even be prognostic implications to the ploidy pattern, particularly in
      borderline tumors, in which nondiploidy portends a poor prognosis.

PMID- 8147212
TI  - Cytology of fluids from pleural, peritoneal and pericardial cavities in children.
      A comprehensive survey.
AB  - We reviewed all cytologic specimens of pleural, peritoneal and pericardial fluids
      examined in our laboratory from patients aged 0-17 years during a 12-year period.
      A total of 103 specimens were studied: 45 pleural, 54 peritoneal and 4
      pericardial. Twenty-two of the 103 specimens were peritoneal washes. Eleven of
      the 81 (14%) serous effusion specimens contained tumor cells: 8 lymphomas, 1
      leukemia, 1 abdominal desmoplastic small round cell tumor and 1 Wilms' tumor. Two
      false-positive diagnoses were made in patients presenting with ascites with an
      unknown case. Both cases were complicated by the presence of atypical mononuclear
      cells and illustrate a potential pitfall in the evaluation of pediatric serous
      effusions. We conclude: (1) Almost all pediatric effusions are benign. (2)
      Malignant pediatric effusions are usually caused by neoplasms of the small cell
      type, mostly lymphoreticular. (3) The major diagnostic difficulty in interpreting
      pediatric effusion cytology is in distinguishing neoplasms of the small cell type
      from mononuclear inflammatory cells. (4) The usefulness of peritoneal washings in
      pediatric patients is similar to that in adults.

PMID- 8147213
TI  - Arias-Stella reaction associated with cervical pregnancy. Report of a case with a
      cytologic presentation.
AB  - We report the case of an Arias-Stella reaction of the cervix presenting in the
      cervical smear from a 35-year-old woman who complained of heavy menstrual
      periods. The smear was originally reported as inconclusive. Colposcopy revealed
      an abnormal transformation zone extending out of range. Cervical conization was
      performed. Histologic examination revealed an ectopic cervical pregnancy
      associated with a cervical Arias-Stella reaction. The cytologic manifestations of
      the Arias-Stella reaction continue to cause diagnostic confusion with benign
      lesions and adenocarcinoma. We believe this to be the first reported case of a
      cervical Arias-Stella reaction associated with a cervical pregnancy; it should
      alert cytologists to the diagnostic implications.

PMID- 8147214
TI  - Cytologic detection of strongyloides stercoralis in a routine cervicovaginal
      smear. A case report.
AB  - A 28-year-old, lactating woman came for a routine checkup. Her cytologic smear
      revealed a single larva of Strongyloides stercoralis. On reviewing the literature
      on parasites encountered in cytologic smears, S stercoralis was found to be
      extremely rare. Our case is probably the second in the world and the first
      reported from India. A review of the literature on various parasites encountered
      in the cytologic smear is presented.

PMID- 8147215
TI  - Papillary carcinoma of the thyroid with numerous spindle-shaped tumor cells in
      fine needle aspiration smears. A case report.
AB  - A papillary carcinoma of the thyroid characterized by numerous spindle-shaped
      tumor cells in fine needle aspiration (FNA) smears is reported. The oval nuclei
      of the spindle cells, arranged in monolayered sheets, occasionally showed
      "rhythmic," palisaded patterns. Comparative study of cytology and histology of
      this tumor revealed that the spindle cells observed in FNA smears originated in
      the epithelium covering the edematous neoplastic papillae.

PMID- 8147216
TI  - Malignant mixed mullerian tumor of the ovary. Report of a case with cytodiagnosis
      by fine needle aspiration.
AB  - An elderly woman with a history of a total hysterectomy underwent fine needle
      biopsy of an ovarian lesion during laparotomy. The cytologic findings
      demonstrated adenocarcinomatous and heterologous sarcomatous cells and were
      reported as a malignant mixed mullerian tumor. A histologic examination confirmed
      this diagnosis.

PMID- 8147217
TI  - Cytologic findings in congenital mesoblastic nephroma. A case report.
AB  - A case of conventional congenital mesoblastic nephroma is presented. The
      characteristic cytologic findings were scant cellularity, a clean background and
      a predominant cell population consisting of naked spindle cells arranged singly
      or in tight, cohesive fragments. Also present were isolated epithelial structures
      -e.g., tubules and glomeruli. They represented native renal structures that were
      entrapped by the tumor as it grew. These tubular and glomerular structures may be
      mistaken for the epithelial component of Wilms' tumor. The cytologic differences
      between congenital mesoblastic nephroma and Wilms' tumor are discussed.

PMID- 8147218
TI  - Malignant melanoma of soft tissue. A report of three cases with diagnosis by fine
      needle aspiration cytology.
AB  - A correlated cytologic and histologic study of three cases of malignant melanoma
      of soft tissue (MMST) is presented. The patients' ages ranged from 21 to 36
      years. Two were females and one, male. In two cases fine needle aspiration
      cytology was done to document local recurrence or metastatic disease and in one
      to establish a primary diagnosis. The cytologic findings were similar in all
      cases. The smears were composed of noncohesive tumor cells with monotonous,
      uniform nuclei, prominent nucleoli and plentiful, light blue cytoplasm.
      Immunohistochemical studies performed in all cases demonstrated staining positive
      for S-100 protein. Electron microscopy from two cases showed premelanosomes and
      melanosomes. These results demonstrate that a precise diagnosis of MMST can be
      rendered on material obtained by aspiration cytology.

PMID- 8147219
TI  - Tyrosine-rich crystalloids in a fine needle aspirate of a polymorphous low grade
      adenocarcinoma of a minor salivary gland. A case report.
AB  - Tyrosine-rich crystalloids were identified in a fine needle aspirate of a
      polymorphous low grade adenocarcinoma of a minor salivary gland. Such
      crystalloids have been described previously as occurring in tissue sections of
      both benign and malignant salivary gland neoplasms and in the fine needle
      aspirate of a pleomorphic adenoma. Their presence either in fine needle aspirates
      or tissue sections of salivary gland tumors should be interpreted only as an
      incidental and nonspecific finding and should not be used to support either a
      benign or malignant diagnosis.

PMID- 8147220
TI  - Intranuclear Reinke's crystals in a testicular Leydig cell tumor diagnosed by
      aspiration cytology. A case report.
AB  - Fine needle aspiration cytologic findings in a Leydig cell tumor of the testis
      are described. Besides the rarity of case reports on fine needle aspiration
      cytologic diagnosis of this tumor, the present case was of interest because of
      the finding of numerous intranuclear and intracytoplasmic Reinke's crystals as
      well as some lying free between the cells. In a few cells the intranuclear
      crystals were seen to orient themselves in a row, with a nipplelike protrusion of
      the nuclear membrane as if being pushed by the crystals. Besides the well-formed
      crystals, many nuclei showed irregular, thin, groovelike spaces that may have
      been earlier stages of crystal formation. These findings suggested the
      intranuclear formation of Reinke's crystals. Extranuclear crystals were seen to
      fuse in pairs and hence to appear thicker than the intranuclear crystals. The
      crystals lying free between the cells also showed a linear arrangement in places.
      The crystals were more numerous with May-Grunwald-Giemsa (MGG) staining.
      Intranuclear crystals were seen only in MGG-stained smears.

PMID- 8147221
TI  - Fine needle aspiration diagnosis of angiomyolipoma of the liver using a cell
      block with immunohistochemical study. A case report.
AB  - Fine needle aspiration diagnosis of hepatic angiomyolipoma has been reported
      rarely. Below we report one such case diagnosed by examination of a cell block.
      The presence of epithelioid smooth muscle cells, mature adipocytes, thick-walled
      vessels and extramedullary hematopoiesis established the diagnosis. It was
      further substantiated by positive staining of the epithelioid cells for muscle
      specific actin (HHF-35). The epithelioid cells were also immunoreactive with a
      melanocytic marker, HMB-45, but not with desmin, vimentin, cytokeratin or S-100
      protein. HMB-45 might prove to be a sensitive marker for the epithelioid smooth
      muscle component of the tumor. The advantage of the routine use of a cell block
      in fine needle aspiration is emphasized.

PMID- 8147222
TI  - Mucinous cystic tumor of the retroperitoneum. A report of two cases.
AB  - Two cases of retroperitoneal mucinous cystic tumors and some diagnostic problems
      on aspiration cytology are presented. The first was a mixed benign, borderline
      and malignant mucinous tumor, and the second was a mixed benign and borderline
      mucinous tumor. Our knowledge of the cytology of ovarian mucinous cystic tumors
      was not helpful in making a correct diagnosis in these cases. Based on our
      experience, we emphasize the following. First, consider methods of collecting
      enough cells to make a diagnosis. Second, consider the possibility of mixed
      histologic features. Direct aspiration, if possible, from papillary lesions
      inside the cyst will probably lead to an accurate diagnosis. Measurement of
      carcinoembryonic antigen levels in the cystic fluid is useful in checking for
      underdiagnosis of such tumors.

PMID- 8147223
TI  - Recurrent hairy cell leukemia presenting as a large mesenteric mass diagnosed by
      fine needle aspiration cytology. A case report.
AB  - A case of hairy cell leukemia (HCL) diagnosed by fine needle aspiration (FNA)
      biopsy performed under computed tomographic (CT) guidance is presented. The
      patient, who had a three-year history of HCL treated with splenectomy and
      interferon therapy, had slowly developed increased abdominal girth. A CT scan
      revealed a large mesenteric mass. FNA was performed on the mass, and immediate
      microscopic examination of this material revealed numerous neoplastic lymphocytes
      with morphologic features consistent with HCL. As a result of the preliminary FNA
      diagnosis, additional appropriate specimens were obtained at the time of the
      aspiration for confirmatory cytochemical, flow cytometric and ultramicroscopic
      studies. This case report demonstrates the utility of FNA cytology in the
      diagnosis of HCL.

PMID- 8147224
TI  - Cervical rib mimicking supraclavicular fossa neoplasia. A case report.
AB  - A case of fine needle aspiration biopsy done on a cervical rib mistaken for a
      supraclavicular lymph node is presented. The significance of identifying a
      cervical rib in the supraclavicular fossa is stressed to avoid subjecting
      patients to unnecessary invasive procedures.

PMID- 8147225
TI  - Congenital cystic adenomatoid malformation of the lung. Report of a case with
      cytologic findings.
AB  - We present the cytologic findings in a case of congenital cystic adenomatoid
      malformation (type II) of the lung in a newborn infant. The patient's condition
      was initially diagnosed in utero as a diaphragmatic hernia. Upon delivery, she
      underwent immediate laparotomy, which revealed no diaphragmatic hernia but rather
      a cystic mass in the left lung. She subsequently developed mediastinal shift and
      severe respiratory distress. A chest tube was inserted, the left cystic mass
      aspirated, and the fluid was examined cytologically. Due to persistent
      respiratory compromise, she underwent thoracotomy with resection of the cystic
      left lung.

PMID- 8147226
TI  - Fine needle aspiration cytology of the tall cell variant of papillary carcinoma
      of the thyroid.

PMID- 8147227
TI  - Fine needle aspiration cytology of metastatic apocrine carcinoma.

PMID- 8147228
TI  - Testicular seminoma and contralateral renal cell carcinoma: diagnosis by fine
      needle aspiration cytology.

PMID- 8147229
TI  - Fine needle aspiration cytology of Sister Mary Joseph's nodule.

PMID- 8147230
TI  - An unusual case of malakoplakia diagnosed by fine needle aspiration cytology.

PMID- 8147231
TI  - The effect of clomiphene citrate isomers on human granulosa-lutein cells in
      culture.
AB  - The effect of racemic clomiphene citrate and its two individual isomeric forms
      (i.e. en and zu) on corpus luteum function was evaluated. Granulosa-lutein cells
      were obtained from three normal ovulatory women undergoing oocyte retrieval
      following ovulation induction with agents other than clomiphene citrate for in
      vitro fertilization--embryo transfer (IVF-ET). The granulosa cells were cultured
      in the presence and absence of the three forms of clomiphene citrate, and in the
      presence and absence of human chorionic gonadotropin (hCG). Patients were
      recruited from the unit for assisted reproductive technology in a university
      hospital. The main outcome measured was the production of estradiol and
      progesterone by cultured human granulosa cells under the various conditions
      described above. The production of estradiol and progesterone by the cultured
      granulosa cells was dose-dependently reduced to a similar extent by all three
      forms of clomiphene citrate. The addition of hCG augmented steroidogenesis in all
      groups at all concentrations, but this still remained lower in all clomiphene
      citrate-treated groups compared to controls. The data suggest that all three
      types of clomiphene citrate (racemic, en, and zu) have inhibitory effects on the
      production of estradiol and progesterone by cultured human granulosa-lutein
      cells.

PMID- 8147232
TI  - The effect of histamine on progesterone and estradiol secretion of human
      granulosa cells in serum-free culture.
AB  - The aim of this study was to explore the direct action of histamine on
      progesterone and estradiol secretion of human granulosa cells cultured in serum
      free medium. Human granulosa cells were isolated from preovulatory follicular
      fluid aspirated from 17 women (32 +/- 3 years old, mean +/- SD) undergoing in
      vitro fertilization treatment at the University Women's Hospital of Tubingen.
      Progesterone and estradiol production was measured in the presence and absence of
      histamine, terfenadine or cimetidine using radioimmunoassays. Statistical
      analysis of the data was performed by analysis of variance and Newmann-Keul
      tests. Histamine stimulated a dose-related increase in estradiol secretion with a
      maximal stimulatory effect at 10(-3) mol/l. This response was blocked
      specifically by the H1-receptor antagonist terfenadine. Progesterone production
      in response to histamine stimulation was independent of dose at the limit of
      significance. The specific H2-receptor antagonist cimetidine did not block the
      stimulatory effect of histamine. We suggest that histamine has a direct
      stimulatory effect on steroid production of granulosa cells mediated via the H1
      receptor. This effect may have a physiological role in the regulation of
      granulosa cell function during the menstrual cycle.

PMID- 8147233
TI  - Human chorionic gonadotropin secretion from the early human placenta: in vitro
      regulation by progesterone and its antagonist.
AB  - Local actions of placental neurohormones and sex steroids have been proposed to
      play a role in the regulation of human chorionic gonadotropin (hCG) release from
      the human placenta. Accordingly, we utilized an in vitro perifusion system and
      cultures of placental explants to investigate short- and long-term effects of
      progesterone and its respective antagonist on hCG secretion from the human first
      trimester placenta. Tissue slices (100 mg) obtained from legal pregnancy
      terminations of 9-12 weeks of gestation were continuously perifused and the
      effluent collected in fractions of 2-20 min. After initial perifusion periods of
      30-140 min, either progesterone, a progesterone antagonist (ZK 98-299), or both
      were added to the perifusion medium at final concentrations of 10(-4)-10(-9)
      mol/l. Administration was either continuous or intermittent in 10-min pulses.
      Furthermore, 50-mg pieces of placental explants were cultured in multiwell tissue
      culture plates for up to 5 days. During the perifusion studies, hCG (determined
      by enzyme immunoassay) was released in a pulsatile fashion. This hCG pulsatility
      was decreased in response to both progesterone and progesterone antagonist at all
      concentrations tested. In contrast, intermittent administration of either
      treatment increased the hCG secretion. Secretion of hCG was not affected when
      progesterone and its antagonist were co-administered at equimolar concentrations.
      These observations demonstrate the diverging effects of progesterone and its
      antagonist on hCG secretion from the human first-trimester placenta in vitro,
      depending on the experimental conditions. Thus, progesterone-modulated hCG
      secretion appears to be regulated in a complex manner, its fine tuning involving
      other, as yet uninvestigated intraplacental factors.

PMID- 8147234
TI  - Differential effects of oral conjugated estrogens and transdermal estradiol on
      insulin-like growth factor 1, growth hormone and sex hormone binding globulin
      serum levels.
AB  - In postmenopausal women oral ethinylestradiol causes a reduction in circulating
      insulin-like growth factor 1 (IGF-1) and an increase in serum growth hormone
      levels. There are no data on the effect of conjugated estrogens, the preparation
      most often used in estrogen replacement treatment (ERT), on these parameters. We
      evaluated serum IGF-1 and growth hormone levels, together with the levels of sex
      hormone binding globulin (SHBG), an indicator of estrogen hepatocellular action,
      before and after 6 months of ERT in two comparable groups of postmenopausal
      women. Sixteen women were treated with oral conjugated estrogens, 0.625 mg/day,
      and 14 with transdermal estradiol, 0.05 mg/day. In the women treated with oral
      conjugated estrogens, an increase in SHBG (p < 0.001), a decrease in IGF-1 (p <
      0.001) and an increase in growth hormone (p < 0.05) serum levels were observed.
      No such effects were seen with the use of transdermal estradiol, devoid of
      hepatocellular effects. Undoubtedly, oral conjugated estrogens, 0.625 mg/day,
      through a hepatocellular effect, cause marked modifications in the IGF-1/growth
      hormone axis, which may have clinical relevance. For instance, the decreased IGF
      1 level, together with the increased level of SHBG, might provide some
      explanation of the favorable epidemiological data on breast cancer risk in women
      receiving oral conjugated estrogens.

PMID- 8147235
TI  - Efficacy, cycle control and side-effects of two monophasic combination oral
      contraceptives: gestodene/ethinylestradiol and norgestimate/ethinylestradiol.
AB  - Two monophasic oral contraceptives containing gestodene (GTD, 75 micrograms) and
      ethinylestradiol (EE, 30 micrograms) or norgestimate (NGS, 250 micrograms) and EE
      (35 micrograms) were compared during the first six cycles of use. The subjects
      were randomly assigned to receive either type: 97 received GTD/EE and 92 NGS/EE.
      Six women in the GTD/EE group and nine in the NGS/EE group withdrew from the
      study; three (3%) and two (2%), respectively, withdrew because of adverse
      reactions. A total of 562 cycles for GTD/EE and 523 for NGS/EE were available. No
      woman became pregnant during the study. Overall, 94.4% of cycles in the GTD/EE
      group and 92.8% in the NGS/EE group were normal. A similar incidence of
      breakthrough bleeding (0.2% of cycles for GTD and 1.6% for NGS) and spotting
      (5.4% vs. 5.6%) was observed. Amenorrhea was never reported. Duration of
      withdrawal bleeding tended to be slightly longer in the NGS/EE group,
      significantly so for cycles 2 (0.5 days, p = 0.016), 4 (0.5 days, p = 0.031) and
      5 (0.4 days, p = 0.045). Cycle 2 was significantly longer in the GTD/EE group
      (0.3 days, p = 0.027). Side-effects were reported by 12 (12%) women in the GTD/EE
      group and 13 (14%) in the NGS/EE group. The most common side-effects were
      headache (five cases (5%) in the GTD/EE group and two (2%) in the NGS/EE group)
      and breast pain (three (3%) and eight (9%) cases respectively). There were no
      statistically significant differences between the two groups with respect to
      change in body weight or changes in blood pressure and in laboratory
      data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147236
TI  - Influence of oral contraceptives on fasting gallbladder volume.
AB  - A total of 615 healthy fertile women (518 pill users and 97 non-users) were
      examined by real-time ultrasonography for fasting gallbladder volume, gallstones
      and biliary dysmorphism. None of the six examined combinations of oral
      contraceptives appeared to influence fasting gallbladder volume significantly.
      When fasting gallbladder volumes were reanalyzed according to the presence or
      absence of recognized biliary risk factors, significant modifications were
      detected, in both pill users and non-users. These changes related only to age and
      parity. Relative risks of cholelithiasis and biliary dysmorphism were not
      affected by contraceptive treatment.

PMID- 8147237
TI  - Endocrinological, ultrasonographic and clinical findings in adolescent and adult
      polycystic ovary patients: a comparative study.
AB  - This study was performed to compare clinical and endocrine features and
      ultrasonographic data of adolescent (< or = 18 years old) and adult (> or = 19
      years old) patients with ultrasound-diagnosed polycystic ovaries (PCOs) in our
      Reproductive Endocrinology outpatient clinic. The adolescent group included 35
      PCO patients while 125 were in the adult group. Hirsutism was present in 64.7% of
      the adolescent group and in 49.6% of the adult group. Menstrual irregularities
      were detected as oligomenorrhea (42.8%), amenorrhea (20%) and irregular but
      normal cycles (17.4%) in the adolescent group; the figures for the adult group
      were 46.4, 8.8 and 23.2%, respectively. These differences were not statistically
      significant. The mean body mass index of the adult PCO group was significantly
      higher than the adolescent PCO group (p < 0.05). The endocrine features
      (estradiol, follicle stimulating hormone, luteinizing hormone (LH), prolactin,
      total testosterone, free testosterone, 17-OH progesterone, androstenedione,
      thyroid stimulating hormone, dehydroepiandrosterone sulfate (DHEAS)) and the
      ovarian volume of both groups were comparable. There was a significant positive
      correlation between ovarian volume and serum LH, total testosterone, free
      testosterone, androstenedione and DHEAS in both groups. We conclude that
      polycystic ovarian syndrome is a disorder with perimenarchal onset, the clinical,
      endocrine and ultrasound features of which will not change by age, although
      patients are prone to gain weight as they get older.

PMID- 8147238
TI  - Thyrotropin secretion before and after ovariectomy in premenopausal women.
AB  - Many studies have shown a physiological reduction in thyroid function with age in
      animals, and less clearly in humans, with an increase in the incidence of age
      dependent clinical and subclinical hypothyroidism. Women are more subject to
      thyroid dysfunction than men. In postmenopausal women the sudden drop in estrogen
      levels may affect not only pituitary gonadotropins but also other pituitary
      hormones directly or indirectly involved in reproductive function. The response
      of thyrotropin to thyrotropin releasing hormone (TRH) has been shown to decrease
      with age and basal levels of thyrotropin have been found to be reduced in elderly
      subjects. In the present study we evaluated the response of thyrotropin to TRH
      before and after ovariectomy in premenopausal women and during estrogen therapy.
      The response of thyrotropin to TRH after ovariectomy was significantly less than
      before. Estrogen replacement therapy restored the thyrotropin response to TRH to
      pre-ovariectomy levels. This significant decrease in the thyrotropin response to
      TRH observed in surgical postmenopausal women may be explained by lower
      endogenous estradiol levels.

PMID- 8147239
TI  - Follicular development and its control.
AB  - The female reproductive cycle is based on a co-ordinated function of several
      regulatory elements and signalling systems. Of the approximately 7 million
      oocytes present in the human fetal ovary, only 475 will eventually ovulate. In
      the human, the development of a primordial follicle into a dominant one takes
      about 10 weeks. Approximately 300 follicles are recruited initially for growth
      and development, 30 of them are likely to become gonadotropin-dependent and enter
      competition for dominance and, finally, only one will achieve ovulation. The
      mechanisms by which follicle stimulating hormone, luteinizing hormone, growth
      factors and steroids may promote or disrupt follicular development are discussed
      in detail. Possible implications of these new facts on diagnosis and treatment of
      ovulatory disturbances are described.

PMID- 8147240
TI  - Prospective European multi-center study of natural family planning (1989-1992):
      interim results. The European Natural Family Planning Study Groups.
AB  - Since 1989 an international multicenter prospective study to evaluate the
      effectiveness and acceptability of natural family planning (NFP) methods in
      Europe has been conducted by the NFP Research Center at the University of
      Dusseldorf in collaboration with the European Zone of the International
      Federation for Family Life Promotion (IFFLP). Fourteen NFP-organizations from
      nine European countries participate in the study. Cycle data from women in the
      fertile age group are transferred to a special standard computer sheet by the
      respective organizations and forwarded at three-monthly intervals to the study
      center for analyses. To date, 10,045 cycles from 900 women aged between 19 and 54
      years have been analyzed. This paper presents the pregnancy rate for the women
      aged between 19 and 45 years of age, who contributed 9284 cycles. In the analyses
      the cycles were subdivided into two categories consequent to sexual practices
      during the fertile phase: group I (NFP only--4277 cycles) use only NFP to avoid a
      pregnancy; group II (FA/mix--5007 cycles) where barrier methods or coitus
      interruptus during the fertile phase, at least in some cycles, were used to avoid
      a pregnancy. The women used different clinical indicators such as basal body
      temperature (BBT), cervical mucus, calculations, cyclical cervical changes or
      combinations of these to determine the beginning and the end of the fertile phase
      necessitating a further division into four subgroups, A, B, C, D, and different
      efficiency rates for each of these groups. In group A (symptothermal method,
      double check) 15 unintended pregnancies (UIP) occurred in 7404 cycles, giving a
      pregnancy rate of 2.4 Pearl Index (PI); in group B (muco-thermal method) there
      were 12 UIP in 1352 cycles with a pregnancy rate of 10.6 (PI); in group C (mucus
      to detect the beginning and mucus and BBT to determine the end of the fertile
      phase) there was one UIP in 434 cycles, and in group D (mucus method only) there
      was one IUP in 70 cycles. The numbers in group C and D are too small to calculate
      a pregnancy rate (PI). No pregnancy was observed in women over 40 years of age.
      Our conclusion from these preliminary results is that in the continent of Europe,
      the symptothermal method when used with periodic abstinence (NFP only = group I)
      and fertility awareness with the use of barriers during the fertile phase (FA/mix
      = group II) are effective methods of family planning.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8147241
TI  - The clinical performance of the Multiload IUD. I. The influence of the
      endometrial cavity length.
AB  - Nine hundred and seventy-four cavimetries were performed using Kurz's Cavimeter
      prior to the insertion of a MLCu375 IUD. In this trial, we studied the
      endometrial cavity length of these women. Results of the cavimetries were
      correlated to IUD complications to determine which uterine sizes were associated
      with IUD side-effects. The expulsion rate was higher for women with an
      endometrial cavity length equal to or greater than 45 mm (p < 0.01) for one and
      two years.

PMID- 8147242
TI  - The clinical performance of the Multiload IUD. II. The influence of age.
AB  - Six thousand four hundred and sixty-two Multiload IUDs were inserted (3606
      MLCu375 and 2856 MLCu250). In this study, we determined the acceptance and safety
      of Multiload IUD use in different age groups. Results were analyzed according to
      the usual life table method. The pregnancy rate was higher with the users of
      MLCu250 than with the MLCu375 in a clear relation to age group. Expulsion and
      bleeding and/or pain rates were higher with younger women in both IUD types.

PMID- 8147243
TI  - Pelvic inflammatory disease and intrauterine devices: prophylactic antibiotics to
      reduce febrile complications.
AB  - In the present study, we tried to determine whether IUD insertion related PID and
      febrile complications could be prevented by prophylactic use of antibiotics. We
      studied 300 patients who were admitted to our family planning clinic for IUD
      contraception. Of these, 150 patients received prophylactic Doxycycline (group 1)
      and the second 150 received no therapy (group 2). Five cases experienced fever
      with or without leucocytosis and none required hospitalization. PID was observed
      in one woman in each group. Positive culture (gonorrhea) was obtained in one
      woman who was then treated by relevant antibiotics; the other woman required
      hospitalization for two days. The overall infection rates for group 1 and 2 were
      2.1% and 2.9%, respectively and this difference was not significant. The
      incidence of PID infection and febrile complications was found to be very low for
      both groups when compared to other studies, suggesting that aseptic conditions
      with proper insertion reduce the risk of infection.

PMID- 8147244
TI  - Nontraumatic tubal occlusion as a new technique for female voluntary
      sterilization.
AB  - Female voluntary sterilization is the most popular method of contraception
      worldwide. It is estimated that around 138 million or 16% of fertile couples,
      have been sterilized by this method. Female sterilization has been widely
      employed in Bali since 1970, in accord with '100' formula. The acceptance rate of
      female sterilization as a family planning method is 7.8% in Bali, and 5.1%
      nationally in Indonesia. But late complications associated with psychosomatic,
      psychosexual and menstrual disturbances are not infrequently found, complications
      attributed to the damage of ovarian blood vessels during the operation. Over the
      years the female sterilization acceptance rate has kept increasing, especially
      among the younger age group (around 30 years). A nontraumatic tubal occlusion
      technique has been developed to preserve the ovarian blood vessel during surgery.
      With the new technique, late complications could be overcome so women could enter
      a normal menopausal period. This new technique described here needs further
      study.

PMID- 8147245
TI  - Tubal sterilization by laparoscopy and mini-laparotomy.
AB  - Laparoscopic tubal sterilization was performed on 179 women using general
      anesthesia, and tubal sterilization via mini-laparotomy was performed in 52 cases
      using local anesthesia. The patients ranged in age from 25 to 41 years, with
      73.2% between 31 and 40 years. The mean operative time of laparoscopy and mini
      laparotomy were 14.2 and 11.6 minutes, respectively. Both the laparoscopy group
      and the mini-laparotomy group were found to be similar with regard to age,
      gravidity and number of abortions. Pelvic inflammatory disease (PID) was not
      observed in any patient during the follow-up period (3 months). Two wound
      infections were detected within the first week following mini-laparotomy, and
      these were treated on an out-patient basis by relevant antibiotics. Among the 179
      patients in whom laparoscopic tubal sterilization was performed, tubal rupture
      occurred in 3 cases (1.67%) which were electrocoagulated easily, and unplanned
      laparotomy was performed in a patient in whom bowel injury during mini-laparotomy
      was suspected.

PMID- 8147246
TI  - Pharmacokinetics and protein binding of 3-ketodesogestrel and gestodene in the
      serum of women during 6 cycles of treatment with two low dose oral
      contraceptives.
AB  - The serum concentrations of 3-ketodesogestrel (KDG) and gestodene have been
      measured in 30 and 31 women respectively who took low dose oral contraceptives
      containing 30 micrograms ethinylestradiol together with either 150 micrograms
      desogestrel or 75 micrograms gestodene for 6 months. On days 1, 10 and 21 of the
      first third and sixth treatment cycles blood samples were drawn at 0, 0.5, 1,
      1.5, 2, 3, 4 and 24 h. KDG and gestodene levels were measured by
      radioimmunoassays and were evaluated for Cmax (peak serum concentration), tmax
      (time to Cmax), and AUC (area under the curve) to 4 and 24 h. The overall total
      gestodene concentrations were higher and the accumulation of the steroid
      throughout a cycle greater than that of KDG. For example, the AUC0-4 of gestodene
      increased in cycle 1 by a factor of 2.8 (day 10 vs. day 1) and 3.6 (day 21 vs.
      day 1) compared to 2.3 and 2.6 for KDG. The higher concentration of gestodene
      reflects a lower volume of distribution than KDG, and is consistent with
      gestodene binding to sex hormone binding globulin (SHBG) with a higher affinity
      than KDG. Concentrations of KDG and gestodene were higher on day 1 of cycles 3
      and 6 than on day 1 of cycle 1. The serum concentrations of KDG and gestodene
      during multiple dosing cannot be predicted on the basis of single dose
      pharmacokinetics.

PMID- 8147247
TI  - Extraovular PGE2 and oxytocin-implicated uterine rupture during midtrimester
      termination of pregnancy.
AB  - A case of uterine rupture caused by extraovular PGE2 in a sequence with
      intravenous oxytocin during midtrimester termination of pregnancy is presented.
      It teaches us that when oxytocin is used after prostaglandins in patients having
      a scarred uterus, the lowest effective dose should be applied.

PMID- 8147248
TI  - A new diagnostic aid for natural family planning.
AB  - INTRODUCTION: We have studied the use-effectiveness of salivary ferning as a
      diagnostic testing aid to natural family planning. We used PG/53, a pocket
      microscope. MATERIALS AND METHODS: Use of natural family planning methods was
      studied in 32 women who used the new technology PG/53 to detect the fertile
      period. By this means the women observed their menstrual cycles and other markers
      of fertility, such as basal body temperature and appearance of cervical mucus.
      RESULTS: Of the 32 women participating in this research, 28 women had a good
      salivary test with positive ferning by the microscope in the same period as other
      markers of fertility. In 4 cycles the ferning was uninterpretable as there was no
      correspondence with the cycle phase. Ferning began 1-2 days before cervical mucus
      appearance, and lasted a mean of 6.2 days. Ferning occurred, on average, 7.2 days
      before the first day of temperature shift. CONCLUSIONS: There is a direct
      correlation between salivary ferning and fertile period. Salivary ferning may be
      used as a new parameter to aid women to detect the fertile period in combination
      with other symptothermal methods of ovulation detection. We now need further
      research in order to improve the use-effectiveness of salivary ferning.

PMID- 8147249
TI  - The pill: perceptions and usage among Nigerian students.
AB  - The knowledge and use of oral contraception were investigated in 498 students
      from 5 tertiary institutions in south-eastern Nigeria. Awareness of the pill was
      high (92.2%) but usage was comparatively low (17.5%). Post-coital oral
      contraception was more often used (11.5%) than the other types. Perceptions about
      the risks of the pill were variable: 46.4% of the students believed that it could
      damage the uterus, and 41% said it could cause infertility; 31.7% believed that
      it caused amenorrhea, while only 14.9% of the students admitted ignorance of the
      risks of the pill. There was a lack of desire to use the pill in 72.3% of the
      respondents. Only 18.7% desired to do so, including students already using the
      pill. The most common source of information on contraception was peer groups
      (43.6%), while lectures and sex instructions constituted the least common source
      (11.2%). Poor information on the pill and ignorance were identified as the major
      factors militating against pill usage. Accordingly, the role of early and
      adequate sex and contraceptive education in improving pill usage in this
      population and developing countries in general is highlighted.

PMID- 8147250
TI  - Attitudes of Czech and Slovak gynecologists toward family planning.
AB  - A survey was held among 155 gynecologists of the former Czech and Slovak Federal
      Republic (CSFR) who visited a national gynecological congress. The sample was
      fairly comparable to the total group of Czech and Slovak gynecologists concerning
      sex, age and county. Questions were asked on personal and professional
      characteristics, experience with the provision of contraception, attitudes toward
      family planning and knowledge about contraception. Almost all gynecologists
      rejected abortion as a birth control method and mentioned the lack of sex
      education, non-use of contraception and the widespread use of traditional
      contraceptive methods as main reasons for the high prevalence of abortion. About
      60% of the physicians thought that at least some women would rather have an
      abortion than use contraception. According to the physicians, special family
      planning services should be developed and delivered by gynecologists. Opinions on
      proper services for teenagers varied. Only a few physicians felt that patients
      should pay the full price of contraceptives. Physicians' knowledge about the pill
      was found to be insufficient. The physicians overestimated the knowledge of their
      female patients about the pill. Apart from books and journals, colleagues and
      pharmaceutical firms were reported as important information sources. Overall, the
      present survey showed that introduction of well structured pre- and postgraduate
      courses in family planning should be encouraged.

PMID- 8147251
TI  - Contraception in Spain.
AB  - This report analyzes various aspects of contraception in Spain. One notable
      finding is the wide socioeconomic, cultural and health variation among regions.
      Since 1975 a significant drop in the birth rate has been observed overall. Twenty
      per cent of the women studied at risk of pregnancy are using oral contraceptives.
      The most widespread contraceptive method is still coitus interruptus, followed by
      oral contraception and the condom, as well as the rhythm method. The highest use
      of oral contraceptive and IUDs is seen in Catalonia (20% and 26% respectively)
      followed by Andalusia, Madrid and Valencia. Although contraception has only
      recently become legal in Spain, it is widely available either without charge or
      very inexpensively; all methods including abortion are available. At present,
      priority is given to special interest groups such as women in special
      circumstances, teenagers, etc. and to special programs like "Integrated Care for
      Women" which includes contraception, STD, pregnancy monitoring, early diagnosis
      of gynaecologic cancer and menopause.

PMID- 8147252
TI  - [Subacute and chronic epidural hematoma after craniocerebral trauma].
AB  - During an 8-year period, fifteen patients with subacute or chronic epidural
      haematoma were seen among 110 treated cases of extradural haematoma corresponding
      to a frequency of 13.6%. Increasing headache, nausea, vomiting, mild drowsiness
      and cranial nerve palsy were the symptoms resulting in the correct diagnosis in
      most cases. Clinical and pathological findings are described, and the factors
      influencing the course of events are discussed. The most important factors are
      cerebral atrophy, age, source of bleeding and location. By means of early CT
      (computed tomography) diagnosis of haematoma, fatal outcome could be prevented in
      most of the cases.

PMID- 8147253
TI  - [Effect of external cervical spine immobilization on intracranial pressure].
AB  - We measured the intracranial pressure (ICP) in 18 patients with severe head
      injury in the neurosurgical intensive-care unit before and after placement of a
      rigid collar for cervical spine immobilisation. The purpose of the study was to
      determine whether the rigid collars, commonly used to, prevent cervical spine
      movement during transport to the treatment facility could lead to an increase in
      ICP. Patients who had an epidural transducer in place were studied and their ICP
      recorded during placement of either the Spieth cervical collar (n = 12) or the
      Philadelphia cervical collar (n = 6). The baseline ICP was 17.0 +/- 6.1 mmHg
      versus 17.7 +/- 6.4 mmHg 10 min after placement of the cervical collar 5 min
      after removal the ICP was 17.2 +/- 5.9 mmHg. No significant changes in ICP could
      be demonstrated during this study. Placement of the cervical collar is a simple
      and practical measure to immobilize the cervical spine during rescue and
      transport of intubated and ventilated patients. Its risk of increasing the ICT
      appears to be low even in the patient with severe head injury.

PMID- 8147254
TI  - [Results of treatment after conservative and surgical management of proximal
      humerus fractures].
AB  - The proximal fracture of the humerus is still the domain of conservative
      treatment. In 80% of our patients the humerus fracture was not operated. The
      remaining 20% were treated surgically. Neer's classification was used for a
      differentiated approach. In case of surgical therapy the guiding principle should
      be to choose the least invasive surgical treatment offering the greatest benefit.
      Minimal treatment should be preferred to prevent necrosis. Further, one should
      strive to gain an axial adjustment of the fracture rather than placing too much
      emphasis on compression. The aim should be an early and graded treatment and an
      early functional therapy. In fractures III, IV and V according to Neer, minimal
      osteosynthesis should be preferred. This will, if the fracture is not accompanied
      by other injuries and if there is adequate physiotherapy after surgery, result in
      a recovery of the function. In relatively young patients with solid spongiosa,
      good stability and anatomical restoration can be achieved by osteosynthesis.
      Unfortunately in fractures II and IV according to Neer, as well as in four
      segment-fractures unsatisfactory results can not be avoided. In such cases
      minimal surgery should be performed. Implantation of a shoulder prosthesis is
      indicated only in case of a secondary painful arthrosis. The only cases in which
      primary alloarthroplasty is indicated are fractures of group II. In these cases
      implantation is promising because of the totally preserved muscular insertion. In
      four-segment and luxation fractures, atraumatic surgical reconstruction should be
      aimed at.

PMID- 8147255
TI  - [Experience with the endoprosthesis in comminuted fractures of the humeral head].
AB  - Surgical treatment is difficult in elderly patients who have suffered a
      comminuted fracture of the head of the humerus, often associated with
      dislocation. We performed follow-up examinations in our hospital in 11 patients
      after implantation of 12 endoprostheses since July 1990. Very good results were
      confirmed in respect of regained freedom of movement and overall high personal
      satisfaction on the part of the patients. Endoprosthesis appears to us as the
      treatment of choice in complex fractures of the head of the humerus in patients
      of advanced age.

PMID- 8147256
TI  - [Surgical management of complete acromioclavicular joint dislocation (Tossy III)
      with PDS cord cerclage].
AB  - 29 patients out of 33 with complete acromioclavicular dislocation treated with
      sewing of ligaments and stabilized with a PDS-cord cerclage could be examined.
      The criteria of examination were subjective complaints while lifting weight,
      limited range of motion in the injured shoulder and radiological results after
      stress with 8 kp. The examination didn't show any relationship between the 3
      parameters. 4 patients with poor function had partly no, partly little complaints
      and if any only little AC-dislocation. On the other hand 4 patients out of 6 with
      remaining AC-subluxation had no complaints and in no case there was a reduced
      range of motion greater than 10 degrees. Three patients got postoperative
      infection of soft tissue or bone, probably caused by incompatibility with PDS
      cord, which led to a fair or poor outcome. Instead of this there can be obtained
      excellent and good results in 75-85% of the cases with this simple method without
      inserting stabilizing metals trans- or extraarticular.

PMID- 8147257
TI  - [Sports capacity after rupture of the anterior cruciate ligament--surgical versus
      non-surgical therapy].
AB  - Using a new rating system (Innsbruck Knee-Sports Rating Scale) 75 patients 5 to 6
      years after ACL-injury have been compared to their sports activity (47 patients
      with ACL reconstruction and 28 conservative treated patients). Under the
      viewpoint of knee load and especially the demand on stability sports activities
      have been divided into 3 categories: High Risk, Low Risk and Non Risk Pivoting
      Sports. Operative therapy shows an advantage in High Risk Pivoting sports (e.g.
      soccer, basketball) and in Low Risk Pivoting (e.g. running, hiking) sports,
      expressed by fewer knee related symptoms and higher participation levels. In the
      Non Risk Pivoting category (e.g. swimming, cycling) good results could also be
      achieved by conservative therapy. The careful evaluation of each patient's sports
      activities is therefore an important factor in the decision for the right therapy
      on one hand, and for comparing the results of different therapy programs or
      patient collectives on the other.

PMID- 8147258
TI  - [Comments on measuring the mobility of the upper ankle joint by the neutral-0
      method].
AB  - The pivot and axes of the ankle joint not easily determined. Instruction and some
      experience are required to determine the values by the Neutral 0 Method as
      accurately and reproducibly as at all possible. The following recommendations are
      based on theoretical considerations and clinical experience: 1. The experienced
      physician can measure the correct angle by taking the patient's foot in his hand
      and asking the patient to raise and lower the foot. From the overall posture and
      reaction of the foot it is possible to correctly "feel" the neutral 0 position as
      initial value, and therefrom the raising and lowering. 2. A highly recommended
      procedure is to examine the patient in recumbent position on the couch with the
      heal upright as it touches the couch. The foot is then lowered until the sole
      touches the couch while the knee is bent, a small supporting board serving to
      determine the axis as the foot is raised. This is a safe method for both the
      beginners and the experienced. The angles can be determined even better than by
      the "free" method. 3. In patients who do not cooperate well, lowering and raising
      of the foot can be checked additionally with the patient standing and bending his
      knee as well as by standing on tiptoe. In this case the passive forces must be
      taken into consideration, especially during forward bending of the lower leg.
      Hence, with this method, it is necessary to distinguish clearly between active
      and passive function.

PMID- 8147259
TI  - [Sequestered bone infection after Kirschner wire osteosynthesis of humeral head
      fracture].
AB  - Percutaneous stabilization of fractures of the humeral head by K-wires is a
      proved therapy. This proceeding provides enough stability for early moving of the
      joint and has a low incidence for complications. In the case described here the
      special is the cause for local infection: local osteonecrosis induced by drilling
      holes too close together.

PMID- 8147260
TI  - [Bone biopsies of cortical bone segments (technique, evaluation)].
AB  - 13 drill biopsies were microscopically examined and evaluated in respect of their
      histologic quality. 8 biopsies were obtained with a diamond hollow cutter, the
      other 5 specimens were sampled with a modified milling cutter according to
      Burkhardt. Regarding proper evaluation of bone biopsies e.g. in cases of
      osteomyelitis, factors as presence of bone marrow cavity or drill powder play an
      important role. Considering these factors the modified milling cutter according
      to Burkhardt yields, precise and careful handling provided, better results than
      the diamond hollow cutter.

PMID- 8147261
TI  - A note on the effect of sulphidopeptide leukotrienes on granulocytes in asthma.

PMID- 8147262
TI  - Cyclosporin: an IL8-binding protein.

PMID- 8147263
TI  - Histamine N-methyltransferase: inhibition by monoamine oxidase inhibitors.
AB  - Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of
      histamine. N tau-Methylhistamine can then undergo oxidation catalyzed by the
      mitochondrial enzyme monoamine oxidase (MAO). Addition of an MAO inhibitor such
      as pargyline to tissue preparations can increase the HNMT activity assayed -
      presumably as a result of inhibition of N tau-methylhistamine metabolism by MAO.
      However, pargyline-dependent "activation" of HNMT may also occur in tissue
      preparations that lack mitochondria. Our experiments were performed to determine
      whether MAO inhibitors, like many other amine compounds, could directly increase
      the activity of partially purified HNMT, and, if so, to study the mechanism of
      activation. Human kidney HNMT was partially purified by sequential ion exchange
      and gel filtration chromatography. The activity of the purified HNMT was
      increased approximately 50% in the presence of pargyline. However, enzyme kinetic
      experiments showed that pargyline, like many other amines, was a competitive
      inhibitor of HNMT. Apparent activation of the enzyme resulted from sequential
      shifts of histamine substrate curves to higher Vmax values in the presence of
      increasing concentrations of pargyline. Other acetylenic MAO inhibitors,
      clorgyline and the two stereoisomers of deprenyl, were also competitive
      inhibitors of purified human kidney HNMT. Inhibition kinetic experiments
      performed in the presence of varying concentrations of histamine demonstrated
      that Kis values for pargyline, clorgyline, (R)-deprenyl and (S)-deprenyl were
      0.126, 0.144, 0.217, and 0.627 mM, respectively. When the concentration of the
      cosubstrate for the reaction, S-adenosyl-L-methionine, was varied in the presence
      of variable concentrations of pargyline, inhibition of HNMT by pargyline was
      noncompetitive with regard to the methyl donor, with Kii and Kis values of 1.23
      and 0.95 mM, respectively. Finally, several amine compounds related structurally
      to pargyline were also found to be inhibitors of HNMT.

PMID- 8147264
TI  - The effect of a cyclooxygenase inhibitor on the in vivo polymorphonuclear
      leukocyte migration to Pseudomonas aeruginosa peptide chemotactins.
AB  - Pseudomonas aeruginosa chemotactic peptides (PAPCs) induced migration of
      polymorphonuclear leukocytes (PMNL) into the lungs when administered by the
      aerosol route. Migration of PMNL into the lungs and total protein content of lung
      lavage fluids in response to PAPCs aerosol challenge, and mortality from lethal
      challenge with P. aeruginosa were decreased by piroxicam treatment.

PMID- 8147265
TI  - Mast cell desensitization to IgE fails to induce a parallel adenosine receptor
      desensitization.
AB  - Desensitization induced by challenge of mast cells with antigen is specific for
      IgE-dependent signals. During the secretory process mast cells release adenosine,
      which can induce a desensitization of adenosine receptors. To determine whether
      adenosine receptors may be desensitized from a previous antigen challenge, mast
      cells were sensitized with anti-DNP IgE antibody, challenged with DNP-BSA
      antigen, returned to culture overnight, resensitized, and rechallenged.
      Previously challenged cells exhibited increased spontaneous beta-hexosaminidase
      release, but adenosine retained its ability to augment beta-hexosaminidase
      release. Adenosine enhanced A23187-stimulated release of beta-hexosaminidase in
      control and previously challenged cells. Leukotriene C4 generation followed a
      similar pattern. Mastoparan, a direct G protein activator and mast cells
      secretagogue, produced a doubling of beta-hexosaminidase release in previously
      challenged cells. Results using other G protein activators were equivocal.
      Degranulation alone is insufficient to induce adenosine receptor
      hyposensitization. Whether the hyperresponsiveness to mastoparan is a consequence
      of uncoupling of IgE receptors from G proteins remains uncertain.

PMID- 8147267
TI  - Influence of acetylsalicylic acid on a Listeria monocytogenes infection.
AB  - The influence of acetylsalicylic acid (ASA, CAS 50-78-2) on the Listeria
      monocytogenes infection in balb/c mice was investigated. One day prior to lethal
      or sublethal infection, balb/c mice were treated intravenously with therapeutic
      concentrations of ASA alone or ASA in combination with murine recombinant
      interferon gamma, a lymphokine produced by T-helper cells. Three days post
      infection, parasite burdens of spleen and liver were determined by the colony
      forming unit assay. It was shown that the prophylactic application of ASA in a
      concentration of 5 mg/kg body weight resulted in a more than 10-fold reduction of
      viable Listeria monocytogenes in spleen and liver of balb/c mice. In addition,
      the combination of a suboptimal dosage of interferon gamma with ASA resulted in a
      significantly higher survival rate compared to the untreated controls.

PMID- 8147266
TI  - Interactions of bradykinin, calcium, G-protein and protein kinase in the
      activation of phospholipase A2 in bovine pulmonary artery endothelial cells.
AB  - Rise in free cytosolic calcium concentrations [Ca2+]i in response to bradykinin
      and guanosine 5'-O-thiotriphosphate (GTP tau S) was related to the action of
      phospholipase A/ (arachidonic acid release). At 900 microM extracellular CaCl2,
      bradykinin induced a typical Ca2+ movement consisting of an initial [Ca2+]i peak
      at approximately 400 nM followed by a sustained increase in the steady-state
      cytosolic Ca2+ level at approximately 290 nM. As the extracellular CaCl2
      concentration was reduced to 100 microM, the bradykinin induced initial spike was
      reduced followed by only a marginal increase in steady-state cytosolic Ca2+
      levels. Treatment of endothelial cells with saponin (0.002% w/w) did not increase
      [Ca2+]i and saponin treated cells exhibited a very similar pattern of Ca2+
      mobilization in response to bradykinin. However, with saponin treatment, GTP tau
      S (100 microM) increased [Ca2+]i at an almost identical tracing exhibited with 50
      nM bradykinin stimulation (in either the presence or absence of 0.002% saponin).
      No additive increase in [Ca2+]i was observed in cells stimulated with both 100
      microM GTP tau S and 50 nM bradykinin or in bradykinin stimulated cells
      subsequently exposed to GTP tau S. Pertussis toxin (PTX) did not affect the
      bradykinin induced Ca2+ mobilization. However, as we showed previously, PTX
      inhibited bradykinin stimulated arachidonic acid release. These results indicate
      transduction of the bradykinin signal by G-protein for both phospholipase A2
      (PLA2) activation and Ca2+ mobilization but likely by different G alpha subunits,
      a PTX sensitive and an insensitive subunit. Furthermore, the bradykinin and GTP
      tau S stimulated release of arachidonic acid appears to be only partially
      dependent on [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147268
TI  - Effect of tetracyclines which have metalloproteinase inhibitory capacity on basal
      and heparin-stimulated bone resorption by chick osteoclasts.
AB  - Several tetracyclines (TETs) are potent inhibitors of collagenase (CGase) and can
      inhibit connective tissue degradation in a variety of inflammatory and
      degenerative disorders. The role of CGase in bone resorption by osteoclasts (OC)
      remains unclear. Disaggregated OCs from chick embryos were cultured for 24 h on
      devitalized bovine cortical bone +/- heparin in the presence of various TETs.
      Doxycycline (Dox) inhibited pit formation in a dose-dependent manner. CMT, a TET
      derivative which inhibits matrix metalloproteinases (MMPs) but is not
      antimicrobial, also inhibited chick OC bone resorption. Heparin markedly
      stimulated bone resorption at 5 micrograms/ml, which was reversed by Dox, 5
      micrograms/ml. TETs can reversibly inhibit both basal and heparin-stimulated bone
      resorption by chick OCs. These findings suggest that MMPs may play a role in
      osteoclastic bone resorption, and that safe and effective inhibitors of MMPs,
      including certain TETs, might have a potential therapeutic role.

PMID- 8147269
TI  - In vitro cardiac pharmacology of the new histamine H2-receptor agonist amthamine:
      comparisons with histamine and dimaprit.
AB  - The cardiac activity of the novel histamine H2-receptor agonist amthamine was
      investigated in a variety of isolated heart preparations from guinea pigs and
      humans and in the isolated rabbit aorta. Amthamine caused an increase in the
      sinus rate of spontaneously beating guinea-pig atria (pD2 = 6.72) and in the
      contractility of the electrically driven guinea-pig papillary muscle (pD2 = 6.17)
      and of the human atrium (pD2 = 5.38). In all these systems, amthamine behaved as
      a full agonist with a potency comparable to or slightly higher than that of
      histamine and 10 times higher than that of dimaprit. The positive effects of
      amthamine were competitively antagonized by ranitidine which had pA2 values (6.46
      and 6.25 in the guinea-pig atria and papillary muscle, respectively) comparable
      with those calculated against histamine and dimaprit. In the isolated rabbit
      aorta amthamine was devoid of H1-mediated activities up to 3 x 10(-4) M. These
      results indicate that amthamine is a potent and selective histamine H2-receptor
      agonist which can be considered a valuable tool for investigating H2-receptor
      mediated effects in cardiac tissues.

PMID- 8147270
TI  - RWJ-22108--a novel airway tissue--selective calcium channel blocker.
AB  - RWJ-22108 is a novel calcium entry blocker that has potential therapeutic use as
      an antiasthmatic agent. Although displaying typical potent inhibition of 45Ca
      uptake into aortic rings (IC50 = 7.1 nM) and displacement of [3H]nitrendipine
      from cardiac membranes (IC50 = 137 nM), RWJ-22108 demonstrates tissue selectivity
      in the inhibition of KCl-induced contractions. RWJ-22108 inhibits the calcium
      dependent contraction of canine bronchiolar smooth muscle with an IC50 of 5.7 nM.
      The IC50 femoral artery/IC50 bronchiolar ratios are 2.85, 8.02, 1.47 and 1.96 for
      nifedipine, RWJ-22108, verapamil, and gallopamil, respectively. Furthermore, this
      selectivity ratio (range 2.8-5.5) of RWJ-22108 is also observed when inhibition
      of other pulmonary and cardiovascular smooth muscles are compared. Using canine
      tracheal muscle and rabbit aortae, the IC50 aorta/IC50 trachea ratio is 1.75 for
      RWJ-22108 compared to approximately 0.5 for several calcium blocker standards.
      These results indicate that in vitro RWJ-22108 is a bronchoselective calcium
      channel blocker.

PMID- 8147271
TI  - Assessment of the in vivo biochemical efficacy of orally active leukotriene
      biosynthesis inhibitors.
AB  - In man, the therapeutic effectiveness of specific inhibitors of leukotriene (LT)
      biosynthesis against allergen-induced bronchoconstriction appears to be related
      to the in vivo biochemical efficacy of these compounds, as measured by inhibition
      of whole blood LTB4 generation (upon A23187 stimulus) and, particularly, urinary
      LTE4 excretion. Accordingly, we have assessed the ability of two clinically
      documented LT biosynthesis inhibitors, zileuton and MK-886, and the structurally
      novel 5-lipoxygenase activating protein antagonist, MK-0591, to inhibit the
      production of these inflammatory arachidonic acid metabolites in laboratory dogs.
      Zileuton (2 mg/kg) was extremely bioavailable in dogs (> 10 microM plasma
      concentrations), and inhibited the A23187-induced ex vivo production of LTB4 by
      venous blood by > 90%, in concordance with its potency in canine blood in vitro
      (IC50 = 1.1 microM). Despite this degree of inhibition in whole blood, urinary
      LTE4 excretion was reduced by only 52%, a profile of activity similar to that
      seen in clinical studies. MK-886 was less well absorbed, with plasma
      concentrations of 3 microM being achieved only at 25 mg/kg. These levels resulted
      in < 45% inhibition of LTB4 production, but a significant (p < 0.05) 47%
      inhibition of urinary LTE4 excretion. MK-0591 was similarly bioavailable
      (compared with MK-886), but 10-fold more active in vivo as a 2 mg/kg dose
      resulted in 41-62% inhibition of urinary LTE4 excretion (p < 0.05 vs controls; n
      = 4, 28). Significant inhibition of ex vivo LTB4 synthesis was also observed at
      this dose (49%), in accord with peak plasma concentrations of 0.5 microM and an
      in vitro potency of 0.2-0.4 microM (IC50) in whole blood from these animals. At
      higher dose (10 mg/kg), MK-0591 inhibited LTE4 excretion by 69%, with 88%
      inhibition of the LT biosynthetic capacity of whole blood. These data demonstrate
      that the biochemical efficacy of structurally diverse leukotriene biosynthesis
      inhibitors can be assessed in vivo in normal laboratory dogs. Such measurements,
      combined with bioavailability data from other species, may be useful for
      predicting biochemical activity in man.

PMID- 8147272
TI  - Altered leukotriene B4 levels by HL-60 cells after monocytic/macrophage
      differentiation.
AB  - The differentiation of HL-60 human promyelocytic leukaemia cells into specific
      monocytic or granulocytic lineage cells depending of the inductor agent is
      accompanied by selective regulation of several key enzymes involved in the
      synthesis of eicosanoids. In this communication we have investigated the changes
      in arachidonic acid metabolic profiles during phorbol 12-myristate 13-acetate
      (PMA)-induced monocytic differentiation of HL-60 cells. Our results show that HL
      60 cells have spontaneous capacity to synthesize large amounts of LTB4, but PMA
      differentiated cells lose the ability to release LTB4. Significant differences
      are found between HL-60 cells and PMA-treated cells in basal conditions and under
      ionophore stimulation. The addition of LTB4 at the time of PMA differentiation
      did not have effects on cell proliferation, but nordihydroguaiaretic acid (NDGA),
      a potent 5-lipoxygenase inhibitor, also inhibited HL-60 cell proliferation and
      did not have any effect on PMA-differentiated cell proliferation.

PMID- 8147273
TI  - Ropivacaine and lidocaine inhibit proliferation of non-transformed cultured adult
      human fibroblasts, endothelial cells and keratinocytes.
AB  - Local anaesthetics are known to affect a variety of cell functions, many of which
      are involved in the inflammatory response. Local anaesthetics have also been
      shown to influence cell proliferation. The aim of this study was to examine the
      effect of two local anaesthetics (ropivacaine and lidocaine) on cell
      proliferation of cultured human fibroblasts, vascular endothelial cells and
      epithelial cells, i.e. keratinocytes, as earlier studies have not included
      primary human cell types. Significant inhibition of fibroblast proliferation was
      observed with concentrations of 50 microM ropivacaine or 100 microM lidocaine in
      1% newborn calf serum and 500 microM ropivacaine or lidocaine in 10% newborn calf
      serum. The proliferation of endothelial cells was significantly inhibited by 1 mM
      ropivacaine in 5% human serum and 500 microM ropivacaine or 100 microM lidocaine
      in 40% human serum. Significant inhibition was not obtained with lidocaine when
      these cells were cultured in 5% HS. Significant inhibition of keratinocytes was
      obtained with 100 microM ropivacaine and 500 microM lidocaine. The effective
      concentrations are within the range of therapeutical concentrations in vivo and
      there seems to be a general correlation between the local anaesthetic potency and
      the inhibiting effect on cell proliferation. This suggest a mechanism by which
      local anaesthetics may exhibit anti-hyperproliferative effects in clinical
      situations.

PMID- 8147274
TI  - The one-ring open hydrolysis product intermediates of the cardioprotective agent
      ICRF-187 (dexrazoxane) displace iron from iron-anthracycline complexes.
AB  - The ability of the cardioprotective agent ICRF-187 (dexrazoxane), its one-ring
      open hydrolysis products, and its two-ring open hydrolysis product, ADR-925, to
      displace Fe3+ from its complex with doxorubicin, daunorubicin, epirubicin and
      idarubicin have been studied. At pH 7.4, ICRF-187 at a concentration of 100
      microM ICRF-187 slowly but completely displaced Fe3+ from its anthracycline
      complexes with half-times ranging from 230 to 450 min. The one-ring open
      intermediate hydrolysis products were also shown to be chelating agents and were
      also able to displace quickly and completely Fe3+ from its anthracycline
      complexes with half-times ranging from 1.7 to 16.7 min. Molecular modeling of
      Fe3+ complexes with the one-ring open intermediates showed that these
      intermediates were likely acting as tetradentate ligands. Since these
      intermediates are such good chelating agents, they may also be pharmacologically
      active species in preventing oxygen-radical derived iron-based anthracycline
      induced cardiotoxicity. Since these one-ring open intermediates are produced by
      hydrolysis from the parent ICRF-187 more quickly than is ADR-925, the formation
      of pharmacologically active species might be occurring more quickly than
      previously thought. The displacement of Fe3+ from its anthracycline complexes by
      the two-ring open hydrolysis product ADR-925 also took place quickly and
      completely with half-times ranging from 1 to 3 min.

PMID- 8147275
TI  - The effect of a synthetic hexadentate iron chelator (CP130) and desferrioxamine
      on rabbit kidneys exposed to cold and warm ischaemia.
AB  - The effect of CP130 (a synthetic hexadentate pyridinone iron chelator) on the
      formation of two markers of lipid peroxidation (TBA-reactive material and
      Schiff's bases) in rabbit kidneys following a 72 h period of cold (0-4 degrees C)
      ischaemia was investigated by either adding CP130 to the flush/storage solution
      (hypertonic citrate solution) or by administering the agent intravenously 15 min
      before removal of the organs. In both cases, CP130 blocked the adverse rises in
      lipid peroxidation caused by ischaemia and subsequent reoxygenation of the
      homogenates in vitro. Both CP130 and desferrioxamine (DFX) (administered
      intravenously 15 min before ischaemia and 5 min before reperfusion) were also
      found to significantly reduce post-ischaemic rates of in vitro lipid peroxidation
      in kidneys rendered warm ischaemic for 90 min followed by reperfusion for 5 or 60
      min in situ. Kidneys exposed to warm ischaemia and reperfusion developed
      interstitial and intracellular oedema, congestion and haemorrhage. DFX
      administration had little effect on the histological outcome, whereas CP130
      significantly reduced interstitial oedema (at 5 min reperfusion compared to the
      DFX-treated group), intracellular oedema (at 60 min reperfusion compared to the
      DFX-treated group) and congestion (at 5 min reperfusion compared with a control
      group not given any agent). It is concluded that while CP130 and DFX exhibited
      similar antioxidant properties, CP130 provided better protection from
      ischaemia/reperfusion injury at the histological level. Synthetic iron chelators
      may therefore be of benefit in clinical organ transplantation by protecting
      against tissue damage caused by prolonged ischaemia.

PMID- 8147276
TI  - Use of drug-specific antibodies to identify ethidium adducts produced in
      Trypanosoma brucei by photoaffinity labeling.
AB  - A photoreactive azido analog of the trypanocide ethidium bromide, 3-amino-8-azido
      5-ethyl-6-phenylphenanthridinium chloride, attached covalently to calf thymus DNA
      (CT DNA) by photoaffinity labeling, was used to generate antibodies for the drug
      analog. The specificity of the antiserum was tested using enzyme-linked
      immunoadsorbant assays (ELISA) against immobilized antigen (photoaffinity labeled
      DNA) and by both the avidin-biotin peroxidase reaction and indirect
      immunofluorescence performed on smears of drug treated trypanosomes. The reaction
      of the antiserum with the covalently bound drug adduct was diminished effectively
      by prior incubation with an excess of ethidium monoazide, ethidium diazide, and
      ethidium bromide, and to a lesser extent by the DNA-ethidium complex, the diazide
      DNA or RNA adduct, and the monoazide-RNA adduct. DNA which had been photoaffinity
      labeled with either the propidium or the acridine moiety did not react. The
      antiserum recognition of DNA photoaffinity labeled with ethidium monoazide was
      based on the substituted phenanthridinium ring system of the parent ethidium, as
      evidenced by competition binding studies involving the free monoazido analog
      (EA1), the diazido analog (EA2), and the parent compound, ethidium bromide (EB).
      This approach and the sensitivity it provides should prove useful for identifying
      the distribution and fate of covalently bound drugs resulting from antiparasitic
      drug treatment, and for studying their roles in antiparasitic action.

PMID- 8147277
TI  - Detection of genetic diversity within snail intermediate hosts of the genus
      Bulinus by using random amplified polymorphic DNA markers (RAPDs).
AB  - A polymerase chain reaction-based polymorphic assay procedure (RAPD) was used to
      study the genetic diversity of intermediate host snails within the genus Bulinus.
      Genetic differentiation was detected between two closely related species: Bulinus
      globosus and Bulinus umbilicatus. Evidence is presented demonstrating the
      potential of RAPD markers for differentiating populations of B. forskalii from
      different countries (Cameroon, Equatorial Guinea and Ivory Coast) or from the
      same country (Cameroon). RAPDs may be also used to identify offspring from cross-
      and self-fertilized hermaphrodite bulinid snails. RAPDs provide a cost-effective
      and routine method for genetic studies of snails transmitting schistosomiasis and
      for the evaluation of diversity between snail populations.

PMID- 8147278
TI  - Nuclear and mitochondrial genetic markers highly conserved between Chinese and
      Philippine Schistosoma japonicum.
AB  - Geographical isolates of S. japonicum, and particularly isolates from China and
      the Philippines, were examined at the molecular level for genetic divergence.
      Sequences from both nuclear and mitochondrial genomes were selected as markers of
      evolutionary divergence and S. mekongi and S. mansoni were included in the study
      for comparison purposes. Restriction fragment length polymorphism (RFLP) and PCR
      RFLP analysis of the rDNA repeat unit and sequence analysis of the second
      internal transcribed spacer region (ITS2) within the rDNA repeat and the
      cytochrome c oxidase I (COI) gene of the mitochondrial genome were performed. No
      intra-specific variation in S. japonicum was found in the rDNA repeat and only
      very slight variation was detected within the COI sequence. A survey of the
      entire genome, using random amplified polymorphic DNA (RAPD) analysis, again
      showed that Chinese and Philippine S. japonicum are remarkably similar at the DNA
      sequence level. We were thus unable to obtain direct molecular evidence in
      support of previous findings, particularly those based on isoenzyme analysis,
      that a very high level of intra-specific variation exists in S. japonicum.

PMID- 8147279
TI  - The prevalence of Plasmodium falciparum and P. vivax in relation to Anopheles
      maculatus densities in a Malaysian village.
AB  - Blood from most of the residents of a remote village in northern peninsular
      Malaysia, bordering Thailand, was examined for malaria parasites monthly for 1
      year. Plasmodium vivax was the commonest infection, but P. falciparum and mixed
      infections also occurred. Monthly collections of the malaria vector, Anopheles
      maculatus showed a positive correlation between mosquito densities and malaria
      positivity in the human population and a negative correlation with rainfall.

PMID- 8147280
TI  - Risk of infection of Wuchereria bancrofti to humans by Culex quinquefasciatus in
      Pondicherry and its relationship with microfilaria prevalence.
AB  - The risk of infection (RI) with Wuchereria bancrofti by vector mosquitoes has
      been conventionally estimated from the biting population of all age classes. This
      estimate of RI had no correlation with microfilaria (mf) prevalence and intensity
      of infection in humans. A new method for estimating RI from a resting population
      of Culex quinquefasciatus is proposed based on a longitudinal study in seventeen
      sites in Pondicherry, India. Unlike previous estimates, RI calculated by the
      present method considering the density of parous mosquitoes collected per man
      hour and the mean number of infective stage larvae per parous mosquito
      significantly correlated with mf prevalence in humans during both early (r =
      0.559; P = 0.038) and late in the control operation (r = 0.572; P = 0.033). RI
      varied significantly between the early and late in the control operation and
      different sites. On average, RI was reduced significantly during the control
      operation. Further epidemiological implications are discussed.

PMID- 8147281
TI  - Dog-bite injuries at a Bangkok teaching hospital.
AB  - Thailand has a large domestic and stray dog population and Buddhist cultural
      beliefs encourage feeding and protection of stray animals. Dog bites are common
      injuries encountered in emergency rooms throughout the country. A prospective
      study of such bites seen at a teaching hospital in Bangkok revealed that: (1) dog
      bites represent 5.3% of injuries seen in the emergency room; (2) the majority
      occur on the street, are inflicated by stray dogs and are interpreted by the
      victim as unprovoked. Children and teenagers account for 55% of the victims. The
      lower extremities (54%) and upper extremities (20%) were the most common sites
      for bites. 9% of patients were bitten on the face or head. In addition to pain,
      risk of infection (approximately 13%) and the significant cost of caring for
      these injuries, victims often experienced prolonged anxiety because of to the
      generally known risk of rabies in Thailand. Due to the high cost of imported
      immune globulins and vaccines, rabies exposures are not always managed optimally
      in Asia.

PMID- 8147282
TI  - A comparison of three methods of estimating EC50 in studies of drug resistance of
      malaria parasites.

PMID- 8147283
TI  - Seasonality of Anopheles aconitus mosquitoes, a secondary vector of malaria, in
      an endemic village near the Malaysia-Thailand border.

PMID- 8147284
TI  - An epidemiologic and economic study of respiratory diseases in two conventional
      Danish swine herds. I: Prevalence of respiratory lesions at slaughter and their
      effects on growth.
AB  - A total of 578 slaughter pigs from 2 Danish conventional farrow-to-finish
      operations (Herds A and B) were followed from an age of 14 days to slaughter.
      Pigs were weighted at 3 weeks intervals and at slaughter and an extended post
      mortem examination of the plucks was done. Comparison of growth rates in pigs
      with and without specific types of lesions by the t-test and those with multiple
      lesions with regression models demonstrated that Mycoplasma-like pneumonia,
      complicated pneumonia, anterio-ventral pleuritis, fissures and atrophic rhinitis
      significantly reduced mean daily gain and increased the time required to reach
      slaughter weight. The total impact of the lesions in Herd A was an estimated
      reduction in mean daily gain of 27 grams and a 2 day increase in the interval
      from 14 days of age until slaughter (MDG14). Decreases in MDG14 in Herd B were
      more substantial, 98 grams and 16.7 days. Reductions in mean daily gains during
      the interval from the fourth weighing until slaughter were 31 grams in Herd A and
      137 grams in Herd B. Chronic dorso-caudal and parietal pleuritis, without other
      lesions present, had no significant adverse effects on growth rates in either
      herd. Interactions between lesions did not significantly alter the estimates. The
      R2 values obtained for the regression models showed that the presence, absence or
      extent of lesions at slaughter explained only 13-27% of the variations in growth
      rates in the 2 herds.

PMID- 8147285
TI  - An epidemiologic and economic study of respiratory diseases in two conventional
      Danish swine herds. II: Associations between lesions present at slaughter and
      mean daily gains during specific intervals of the growth period.
AB  - A total of 578 slaughter pigs from 2 Danish conventional farrow-to-finish
      operations (Herds a and B) were followed from an age of 14 days to slaughter.
      Pigs were weighted at 3 weeks intervals and at slaughter and extended post mortem
      examination of the plucks was done. Regression models with second and third order
      interaction terms demonstrated that Mycoplasma-like pneumonia, complicated
      pneumonia, anterior-ventral pleuritis, pericarditis, fissures and atrophic
      rhinitis, separately and through interactions with other lesions, significantly
      reduced mean daily gains during specific intervals of the growth period in 2
      conventional swine herds. It is likely that the periods of reduced growth reflect
      the times when the diseases were in the acute and early recovery stages. Maximum
      estimated reductions in daily gains associated with the combined lesions were 82
      grams and 283 grams during the interval 120-140 days in Herds A and B,
      respectively. Although dorso-caudal pleuritis and parietal pleuritis had minor
      negative effects during 2 intervals neither had a significant adverse effect on
      total growth rate in either herd (Paisley et al. 1993). R2 values for the
      regression models were less than 0.27 showing that the lesions present at
      slaughter explained less than 27% of the variation in herd mean daily gains
      during any interval.

PMID- 8147286
TI  - Development of clinical signs and occurrence of feline corona virus antigen in
      naturally infected barrier reared cats and their offspring.
AB  - The onset and pattern of the clinical signs of feline corona virus (FCoV)
      infection in cats were studied in a setting behind an isolation barrier. Two FCoV
      seropositive cats were the source of the infection, and 3 barrier reared cats -
      initially FCoV-seronegative - were the recipients. The first clinical sign in the
      recipients appeared 11 days after contact with the source of infection. After 2
      years 1 male and 1 female of the recipients started to breed. Their offspring
      developed clinical signs of disease at an age of 4-5 weeks. A pattern of
      recurring upper respiratory tract signs and conjunctivitis at intervals of about
      4 months was observed in both the recipients and their offspring, while CNS
      dependent signs and wasting remained or got worse, once developed. Once
      demonstrated, FCoV antigen persisted in membrana nictitans throughout the
      investigation, and was found in all cats but 4 (90%). The offspring died during 2
      periods, around the first week of life (9/37), and at 3-5 months of age (5/25).
      For comparison 3 offspring were euthanized at an age of 1 day and 16 offspring at
      an age of 3-6 months. FCoV antigen was demonstrated in all organs investigated
      (100%) from offspring dying during the first period, and in 97% from those dying
      during the second period. For the offspring euthanized during the same 2 periods
      the corresponding findings were 95% and 85%. Offspring euthanized between 9 and
      17 months (4 kittens) had antigen in 67% of all investigated organs. The
      incidence of FCoV antigen in almost every organ in the investigated newborn
      kittens suggests an intrauterine infection. The demonstration of FCoV antigen in
      all euthanised cats, suggests a persistent infection. Virus was cultivated from
      membrana nictitans, that was FCoV antigen positive in the M3 test.

PMID- 8147287
TI  - Calcification of intervertebral discs in the dachshund: an estimation of
      heritability.
AB  - The heritability of calcified intervertebral discs in the dachshund was estimated
      using data gathered from a radiographic study. Radiographs of the vertebral
      columns of 274 clinically normal, 12 to 18 months old dachshunds, were examined.
      The dogs were offspring from 75 different sires, representing the same number of
      half sib groups. There were 2 to 14 offspring in each half-sib group. The number
      of full sib groups was 81. Calcified intervertebral discs were identified in
      20.4% of the dogs. An analysis of variance that used the data as a continuous and
      as an either/or-variable estimated the heritability of calcified discs to be 0.22
      and 0.15 respectively. A genetic factor was found to be essential for the
      occurrence of calcified discs in a dog while a common environmental factor
      presumably resulting from non-genetic causes was significant in determining the
      number of discs to undergo calcification in affected dogs.

PMID- 8147288
TI  - Mutagenicity, creatine and nutrient contents of pan fried meat from various
      animal species.
AB  - The mutagenic activity in extracts of fried meat from 16 different animal species
      was studied in Salmonella typhimurium TA98. In each experiment, 1 meat sample
      together with a standard beef sample was fried, and the mutagenicity was
      expressed relative to the beef sample. All meat samples showed less mutagenic
      activity than beef. The contents of creatine, creatinine, water, protein,
      carbohydrate and fat in the meat samples were analyzed, but mutagenicity was not
      correlated with the concentration of any of these constituents. Beef meat treated
      with creatinase to remove creatine produced reduced mutagenic activity. Possibly
      a threshold concentration of creatine is necessary to give a high mutagenic
      response.

PMID- 8147289
TI  - Abortion and calf mortality in Danish cattle herds.
AB  - The aetiology of abortions and calf mortality in 65 Danish cattle herds
      consisting of both dairy and beef breeds during a 1-year period is described. All
      observed aborted foetuses, still-born calves, and calves dying before 6 months of
      age were necropsied, and relevant microbiological examinations were performed. A
      total of 240 calves and 66 abortions were submitted corresponding to a calf
      mortality rate of 7%. The abortion frequency could not be calculated. 43% of the
      calves died at day 0, while 22% were aborted, 15% died during the first week of
      life, 9% died from 1 to 4 weeks of age, and 11% died at the age of 1 to 6 months.
      The most common cause was neonatal pulmonic atelectasis (stillbirth) followed by
      foetal infections, pneumonia, and septicaemia.

PMID- 8147290
TI  - Vertebral fractures in newborn calves.
AB  - A prospective study on vertebral fractures in newborn calves is described.
      Vertebral fractures were found in 7.0% of necropsied calves of the Danish
      Holstein-Friesian (SDM) and Red Danish Dairy (RDM) breeds. Cases were not found
      in submitted calves of the Jersey breed or beef breeds. At least in beef breeds
      this was probably due to the low number necropsied. The rate of vertebral
      fractures in SDM and RDM breeds and between males and females were similar. Most
      cases occurred in calves born by heifers, and manual traction force had been
      applied in all cases. All fractures which in most cases consisted of a simple
      epiphysiolysis were located at the thoraco-lumbar area, and especially the
      posterior epiphysis of T13 was afflicted.

PMID- 8147291
TI  - Diseases and injuries associated with mortality of hatchery reared Baltic cod
      (Gadus morhua L.) larvae.
AB  - A cod hatching plant was established in 1992 on the island of Bornholm in the
      Baltic Sea in order to elucidate the possibilities for restocking of cod fry in
      this brackishwater system. The disease prevalence in 3 batches of hatchery-reared
      yolksac larvae from the Baltic cod (Gadus morhua L.) was monitored during the
      posthatch period. High prevalences of bacteriosis/mycosis, lordosis/scoliosis,
      injuries and protozoan endoparasitism were recorded. Vibrio sp. and Vibrio
      anguillarum serovar 04, 06, 08 in addition to nontypable strains and
      saprolegniaceous fungi were isolated from the larvae. The dinoflagellate-like
      endoparasites were located in the yolksac of the cod larvae.

PMID- 8147292
TI  - The occurrence of Salmonella in airline meals.
AB  - The occurrence of Salmonella in airline meals was studied in 1989-1992. Samples
      were collected from flight kitchens in 29 countries. The material consisted of
      400 cold dishes and 1,288 hot dishes as well as salads, cheese plates and
      deserts. Total number of samples was 2211. Salmonella spp. were isolated from 6
      samples; 1 contaminated sample was a cold dish prepared in Bangkok, 1 was a hot
      dish prepared in Mombasa and the remaining 4 contaminated samples were hot dishes
      prepared within one week in Beijing. The isolated serotypes were S. ohio, S.
      manchester and S. braenderup. The contaminated cold dish prepared by a flight
      kitchen in Bangkok was found to be connected with a Salmonella outbreak which
      occurred in Finland in 1990. Cold airline dishes containing food of animal origin
      seems to be more risky as a source of Salmonella infections among airline
      passengers.

PMID- 8147293
TI  - Effect of dietary magnesium on post mortem phosphocreatine utilization in
      skeletal muscle of swine: a non-invasive study using 31P-NMR spectroscopy.
AB  - The effect of dietary magnesium on the post mortem PCr (phosphocreatine) decay in
      muscle of heterozygote malignant hyperthermia pigs was studied after in vivo
      exposure to a combination of halothane and succinylcholine. The pigs were
      anaesthetized with halothane and succinylcholine was injected in the ear vein.
      Immediately after initiation of the depolarizing neuromuscular blocking effect of
      succinylcholine the animals were captive-bolt stunned. The PCr decay, reflecting
      ATP turnover, was followed in situ by 31P-NMR spectroscopy in the biceps femoris
      muscle for the subsequent 40-70 min post mortem. In 3 of the 4 experiments, the
      Mg-fed pig had a significantly reduced rate of PCr hydrolysis compared to the
      control animal. The mechanism of this magnesium effect is unknown.

PMID- 8147294
TI  - Reduced response to intravenous endotoxin injections following repeated oral
      administration of endotoxin in the pig.
AB  - Three prepubertal gilts were each given 100 mg of endotoxin (ET) in their
      ordinary feed rations, twice daily for 6 days; 3 other gilts received standard
      feed. Following ET feeding, all animals were injected intravenously (i.v.) with
      ET (1.0 microgram/kg b.w.) once daily for 5 days. Blood samples were collected
      and analysed for hematology and total serum bile acids (S-BA), glutamate
      dehydrogenase (S-GLDH), calcium (S-Ca), iron (S-Fe), zinc (S-Zn) and a blood
      plasma metabolite (15-ketodihydro-PGF2a; P-PG) of prostaglandin F2a. The animals
      showed no apparent clinical symptoms following ET-feeding, neither did the blood
      analyses reveal effects of oral ET. However, when iv ET injections were given,
      the ET-fed animals showed fewer clinical signs of endotoxemia following the 2nd
      to 5th injection. S-BA and S-GLDH increased markedly in the standard-fed group
      following the first injection, while the ET-fed animals showed a much smaller
      increase in S-BA and no change in S-GLDH on that day. The difference in response
      may be explained by a direct uptake of ET from the gastrointestinal tract in the
      ET-fed pigs, making them less sensitive to the injected ET.

PMID- 8147295
TI  - Value of metabolic imaging with positron emission tomography for evaluating
      prognosis in patients with coronary artery disease and left ventricular
      dysfunction.
AB  - Patients with coronary artery disease (CAD) and severe left ventricular (LV)
      dysfunction have a high but variable annual mortality and some may benefit from
      myocardial revascularization. This study aimed to evaluate the prognostic value
      of positron emission tomography (PET), and its interrelation with the choice of
      medical therapy or revascularization for predicting survival and improvement in
      symptoms of heart failure in patients with CAD and LV dysfunction. Ninety-three
      consecutive patients with angiographic CAD and a mean LV ejection fraction of
      0.25 who underwent cardiac PET studies for assessment of hypoperfused yet viable
      myocardium ("mismatch pattern") using N-13 ammonia and 18-F deoxyglucose were
      followed up for an average of 13.6 months. Fifty patients underwent medical
      treatment and 43 underwent revascularization. The Cox model analysis showed that
      the extent of mismatch had a negative effect (p = 0.02), whereas
      revascularization had a positive effect on survival (p = 0.04). The annual
      survival probability of patients with mismatch receiving medical therapy was
      lower than of those without mismatch (50 vs 92%, p = 0.007). Patients with
      mismatch who underwent revascularization had a higher survival rate than those
      treated medically (88 vs 50%, P = 0.03). The presence of mismatch also predicted
      improvement in heart failure symptoms after revascularization (p < 0.001). These
      results suggest that the presence of mismatch in patients with CAD and severe LV
      dysfunction is associated with poor annual survival with medical therapy.
      Revascularization in patients with PET mismatch appears to be associated with
      improved survival and heart failure symptoms.

PMID- 8147296
TI  - Usefulness of transesophageal atrial pacing combined with two-dimensional
      echocardiography (echo-pacing) in predicting the presence and site of residual
      jeopardized myocardium after uncomplicated acute myocardial infarction.
AB  - The usefulness of transesophageal atrial pacing combined with 2-dimensional
      echocardiography (echo-pacing) in predicting the presence and site of jeopardized
      myocardium, defined as areas of myocardium perfused by a vessel with a stenosis >
      or = 75% or by a collateral circulation if the supplying vessel was occluded, was
      evaluated in 31 patients with uncomplicated acute myocardial infarction who
      underwent coronary angiography. All 5 patients without jeopardized myocardium had
      a negative test, whereas 24 of 26 with jeopardized muscle had a positive test
      (sensitivity 92%; specificity 100%). To identify the site of jeopardized
      myocardium, tests that were positive for development of new asynergies were
      analyzed further, distinguishing those positive in the infarct or remote zone.
      Seven of 8 patients with new asynergies in the remote zone had areas of
      jeopardized myocardium outside the territory of distribution of the infarct
      related vessel, whereas only 2 of 12 with new asynergies in the infarct zone had
      areas of jeopardized myocardium outside that territory (p < 0.01), correctly
      predicting the site of jeopardized myocardium in 17 of 20 cases. In conclusion,
      echo-pacing is useful for detecting the presence and site of jeopardized
      myocardium after an acute myocardial infarction.

PMID- 8147297
TI  - Incidence and time course of left ventricular dilation in the early convalescent
      stage of reperfused anterior wall acute myocardial infarction.
AB  - The incidence and early process of left ventricular (LV) dilation in 52 patients
      with reperfused anterior wall acute myocardial infarction (AMI) were assessed.
      All patients achieved coronary reflow within 24 hours of the onset and had a
      patent infarct-related artery in the convalescent stage. Left ventriculography
      was performed at pre-reflow and 25 days (mean) later to determine LV end
      diastolic volume (ml) with the area/length method. Short-axis echo images at the
      midpapillary muscle level were recorded at days 1, 7, 14, and 28 of the AMI. With
      use of the papillary muscles as the internal landmarkers, the LV wall was divided
      into the anterior and posterior segments, and length and thickness of each
      segment were determined. Among 52 patients, 10 (19%) had a > or = 20% increase in
      end-diastolic volume in the convalescent stage. Echocardiographic studies
      demonstrated that there were no significant changes in lengths and thicknesses of
      the anterior and posterior segments during follow-up study relative to his or her
      baseline value in 42 patients without LV dilation. In the patients with LV
      dilation, however, the anterior segment exhibited a mean increase of 25% in its
      length with a mean decrease of 21% in its thickness at day 7 relative to their
      baseline values, but no progressive expansion was observed after day 7. A mean
      increase of 7% in the posterior segment length without reduction in its thickness
      first became evident at day 28.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147298
TI  - Differences in clot lysis among patients demonstrated in vitro with three
      thrombolytic agents (tissue-type plasminogen activator, streptokinase and
      urokinase).
AB  - This study compares the ability of 3 thrombolytic drugs to promote clot lysis
      using a new in vitro testing procedure. Whole blood samples from 132 patients
      were tested using 5 different concentrations of tissue-type plasminogen activator
      (t-PA), streptokinase (SK) and urokinase. A mixture of blood and thrombolytic
      drug was placed on a dry-reagent test card containing reptilase, buffers and
      paramagnetic particles where clot formation occurred. Analysis of the motion of
      the clot-embedded paramagnetic particles caused by an oscillating magnetic field
      was used to define the lysis onset time. The slope of the linear regression plot
      of lysis onset time versus 1/[drug concentration] defined the kinetic rate
      constant (k) for each drug in each patient. Higher values of k indicated greater
      resistance to in vitro clot lysis. In the patients studied, there was a large
      range of k values for t-PA and SK (coefficient of variation 143 and 137%,
      respectively) but a smaller range of k for urokinase (coefficient of variation
      32%). The coefficients of variation for t-PA and SK observed in the study group
      were five- to 10-fold greater than the coefficients of variation determined for
      replicate test measurements. Resistance to all SK concentrations tested was found
      in 9% of the patients. In vitro sensitivity to thrombolysis was compared among
      the drugs by correlating the derived k values. These comparisons indicated no
      relation for any of the drugs; many patients had a relatively low k value for 1
      drug, while having a relatively high k value for a different drug.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8147299
TI  - Impact of the electrocardiogram on the delivery of thrombolytic therapy for acute
      myocardial infarction.
AB  - The initial electrocardiogram is crucial in accurately selecting patients with
      chest pain for thrombolytic therapy. An electrocardiogram with a large amount of
      ST-segment elevation and depression is "visually alarming," and therefore, may
      influence the efficiency of patient treatment with thrombolytic therapy. It was
      hypothesized that the amount of ST-segment deviation present on the initial
      electrocardiogram was an important variable in determining the time to initiation
      of thrombolysis in the emergency department. The time from arrival at the
      emergency department to thrombolysis was measured in 93 consecutive patients with
      suspected acute myocardial infarction (AMI) who were treated with intravenous
      thrombolytic therapy by emergency department physicians. This was correlated with
      the sum of ST-segment elevation and depression present on the initial
      electrocardiogram. AMI was proved in 83 patients (89%). In patients with proved
      AMI, the average time to thrombolysis was 50.8 +/- 25.6 minutes. Treatment began
      within the goal of < or = 30 minutes in 18 patients (22%) and was excessively
      delayed at > or = 60 minutes in 24 (29%). Regression analysis of multiple
      clinical variables revealed that ST-segment sum was the only variable that
      significantly influenced the time to thrombolysis (r = -0.42; p < 0.001). For
      patients treated in < or = 30 minutes, the average ST-segment sum was 21.1 +/-
      13.5 vs 11.5 +/- 11.4 mm for those treated in > or = 60 minutes (p = 0.01). In 10
      patients mistakenly treated with thrombolytic therapy, the electrocardiographic
      processes responsible for ST-segment elevation included the early repolarization
      variant, left ventricular hypertrophy, old anterior AMI with persistent ST
      segment elevation, and conduction delay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147300
TI  - Ventricular fibrillation induced by low-energy shocks from programmable
      implantable cardioverter-defibrillators in patients with coronary artery disease.
AB  - Many of the newest implantable cardioverter-defibrillators (ICDs) provide the
      option of programmable low-energy cardioversion for monomorphic ventricular
      tachycardia (VT). Whereas these devices may provide less myocardial damage and
      increased comfort in patients receiving frequent shocks for VT, the proarrhythmic
      effects of low-energy cardioversion from ICDs in patients with structural heart
      disease are not clear. The purpose of this study was to determine prospectively
      the per-patient incidence of ventricular fibrillation (VF) induction after low
      energy cardioversion of VT by ICDs in patients with coronary artery disease. The
      estimated cardioversion energy requirement was determined during the course of
      routine predischarge ICD testing in 40 patients with newly implanted ICDs. Two
      groups of patients were identified during determination of the cardioversion
      energy requirement: (1) a non-VF group consisting of 26 of 40 patients (65%)
      without VF induced by low-energy shock and, (2) a VF group consisting of 14 of 40
      patients (35%) who developed VF during low-energy cardioversion. There was no
      difference between the 2 groups in terms of patient age, sex, concurrent
      antiarrhythmic drug therapy, VT cycle length, or type of ICD system implanted.
      Compared with the non-VF group, the VF group was more likely to have both a lower
      ejection fraction (25 +/- 5% vs 33 +/- 8%; p = 0.005) and a cardioversion energy
      requirement > 2 J (79 vs 27%; p = 0.005). Our results suggest that low-energy
      cardioversion is associated with a high per-patient risk of VF induction, and the
      risk is higher in patients with poorer left ventricular function and, possibly,
      higher cardioversion energy requirement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147301
TI  - Ethnic differences in electrocardiographic left ventricular hypertrophy in young
      and middle-aged employed American men.
AB  - In the United States population, black men have higher prevalence rates of
      electrocardiographic (ECG) high QRS voltage, more ST-segment and T-wave
      abnormalities, and more ECG left ventricular hypertrophy (LVH) than do white men.
      Reasons for these differences have not been fully elucidated. The prevalence rate
      of ECG LVH and associated characteristics were compared in black and white men in
      the Chicago Heart Association Detection Project in Industry population study.
      Data were from 1,391 black men and 19,126 white men (age range 20 to 64 years)
      employed by 84 Chicago organizations. ECG LVH was defined by the presence of both
      high QRS (Minnesota code 3.3) and ST-T abnormality (code 4.1-4.3 or 5.1-5.3).
      Black men had a significantly higher prevalence rate of ECG LVH than did white
      men in each 15-year age group (15.9 vs 2.4, 14.6 vs 2.8, and 35.7 vs 12.5/1,000
      in the 20- to 34-, 35- to 49-, and 50-to 64-year age groups, respectively; p <
      0.01 for each comparison). Multiple logistic regression analyses indicated that
      systolic blood pressure and age were associated positively with ECG LVH (p <
      0.01) in both black and white men. Men with history of hypertension and receiving
      drug treatment had a greater likelihood of having ECG LVH than did those with
      history of hypertension but not receiving drug treatment, possibly because those
      with more severe hypertension were more likely to have been prescribed
      medication. Serum cholesterol, cigarettes smoked/day, 1-hour post-load plasma
      glucose and education were not consistently related to ECG LVH.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8147302
TI  - Predictive value of prominent pulmonary arterial wedge V waves in assessing the
      presence and severity of mitral regurgitation.
AB  - Indwelling pulmonary arterial catheters are often used to monitor and to guide
      therapy in critically ill patients. The magnitude of the V wave recorded from the
      pulmonary arterial wedge (PAW) position is sometimes used to assess the presence
      and severity of mitral regurgitation (MR). The present study was performed to
      assess the relation (or lack thereof) between a "prominent" PAW V wave and
      qualitative and quantitative estimates of MR. In 903 subjects (445 men and 458
      women, aged 49 +/- 13 [mean +/- SD] years) referred for cardiac catheterization,
      an oximetrically confirmed PAW pressure was recorded with a large-lumen stiff
      catheter, and a left ventriculogram was recorded. In 646 of these subjects (328
      men and 318 women, aged 50 +/- 13 years), forward cardiac output was measured by
      the Fick principle, and a regurgitant fraction was calculated. Prominent PAW V
      waves--as defined in several ways--were insensitive and had poor positive
      predictive value in identifying moderate or severe MR. At the same time, the
      absence of prominent PAW V waves was relatively specific for the absence of
      moderate or severe MR, and the negative predictive value of small V waves was
      very good. Thus, the prominence of a PAW V wave cannot be used to assess the
      presence or severity of MR.

PMID- 8147303
TI  - Results of permanent dual-chamber pacing in symptomatic nonobstructive
      hypertrophic cardiomyopathy.
AB  - Because dual-chamber (DDD) pacing has been shown to be of benefit regarding
      symptoms, rest and pacing hemodynamics, and exercise duration in patients with
      obstructive hypertrophic cardiomyopathy (HC), the effect of DDD pacing was
      assessed in patients with nonobstructive HC who were significantly symptomatic
      despite medical management. Echocardiography, treadmill exercise testing,
      thallium-201 scintigraphy, radionuclide angiography, and invasive measurement of
      rest and semi-erect bicycle exercise hemodynamics were performed in 12 patients
      before and approximately 4 months after permanent DDD pacing. One patient died 3
      months after pacemaker implantation, because of worsening diastolic heart
      failure. Of the remaining 11 patients, 10 improved regarding symptoms, and
      treadmill exercise duration was longer during DDD pacing than during the baseline
      study in sinus rhythm (6.8 +/- 2.8 to 8.5 +/- 2.8 minutes; p < 0.01), with a
      significant increase in the peak double product achieved (28.9 +/- 6.1 to 31.0 +/
      6.8 x 10(3); p < 0.05). However, there were significant reductions in cardiac
      (3.7 +/- 0.9 to 3.1 +/- 0.5 ml/min/m2; p < 0.01) and stroke volume (47.4 +/- 11.4
      to 38.7 +/- 6.5 ml/beat/m2; p < 0.01) indexes, and a trend toward reduction in
      submaximal stroke volume index during DDD pacing as compared with the baseline
      study in sinus rhythm (44.7 +/- 13.5 to 40.9 +/- 10.9 ml/beat/m2; p = 0.097). No
      change in peak heart rate, cardiac or stroke volume index, mean blood pressure,
      or pulmonary artery or pulmonary capillary wedge pressure occurred with peak
      exercise during DDD pacing as compared with the initial exercise study in sinus
      rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147304
TI  - Prevalence of hypertrophic cardiomyopathy in an outpatient population referred
      for echocardiographic study.
AB  - Although hypertrophic cardiomyopathy (HC) is believed to be a relatively uncommon
      cardiac disease, the frequency with which it occurs in the general or cardiac
      population has not been defined. To address this issue, the patient population of
      a community-based echocardiography laboratory was used to assess the prevalence
      of HC in 714 consecutively studied outpatients with (or suspected of having)
      heart disease. The most common cardiac disease identified was mitral valve
      prolapse (73 patients [10%]), and HC was present in 4 patients (0.5%). Ages were
      50 to 69 years. Maximal left ventricular wall thicknessess were 15 to 22 mm (mean
      19); only 1 had evidence of obstruction to left ventricular outflow by virtue of
      marked mitral valve systolic anterior motion. Before echocardiographic study,
      each of the 4 patients with HC had signs or symptoms of cardiac disease, but the
      correct diagnosis had not been suspected. Of 11 other patients who were referred
      for echocardiographic study because of a clinical suspicion of HC, none proved to
      have this disease. The present study demonstrates that HC is a particularly
      uncommon disease entity occurring in about 0.5% of an unselected outpatient
      population referred for echocardiographic study.

PMID- 8147305
TI  - Asplenia syndrome: insight into embryology through an analysis of cardiac and
      extracardiac anomalies.
AB  - Asplenia syndrome is characterized by complex congenital heart defects, asplenia
      and abdominal heterotaxy. Recent interest in the syndrome has been increased by
      new knowledge arising from animal models and by continuing improvements in
      surgical outcome in childhood. To further elucidate the embryologic timing and
      mechanisms of the asplenia syndrome, 32 necropsy cases were reviewed and 487
      published autopsy cases were reanalyzed at the hospital. The most common
      congenital heart defects were atrial septal defects, common atrioventricular
      canals and conotruncal anomalies. With use of current information on the timing
      of normal development, it was hypothesized that most defects originate at
      Streeter Horizon XIII; patients averaged 3.2 Horizon XIII defects, more than at
      any other stage. Distribution was unimodal. Extracardiac anomalies also exhibited
      a developmental spectrum. Because the normal spleen develops by Horizon XIII,
      asplenia, the sine qua non of the syndrome, originates then or earlier. Abnormal
      pulmonary lobation occurred in 80% of cases, with right isomerism occurring most
      often; pulmonary branching asymmetry also originates at or before Horizon XIII.
      Abdominal heterotaxy occurred in 72% of cases, but the timing of origin is
      unclear. Anomalies of other systems, including genitourinary, musculoskeletal,
      endocrine, and nervous systems, develop later (typically XV to XXIII); specific
      anomalies were less frequent, although much more prevalent than in the general
      population. It is concluded that asplenia syndrome is a focal developmental
      disturbance in laterality which occurs primarily at Horizon XIII.

PMID- 8147306
TI  - Comparison of right ventricular systolic function in idiopathic dilated
      cardiomyopathy and healed anterior wall myocardial infarction associated with
      atherosclerotic coronary artery disease.
AB  - A case-controlled study assessed right ventricular (RV) systolic function in 10
      patients with idiopathic dilated cardiomyopathy (IDC) and in 10 with healed
      anterior wall myocardial infarction associated with atherosclerotic coronary
      artery disease (CAD). Each patient was matched for sex, left ventricular ejection
      fraction +/- 5% and pulmonary artery mean pressure +/- 5 mm Hg. All patients had
      sinus rhythm and a left ventricular ejection fraction < 45%. A new, well
      validated thermodilution technique was used to assess RV ejection fraction and
      volumes. RV ejection fraction was lower in the IDC than in the CAD group (25 +/-
      14% vs 36 +/- 11%; p < 0.02). Linear correlations between RV parameters and
      pulmonary artery pressure were significantly present in both groups. However, the
      slopes of the equations were not statistically different. In comparison with
      healed anterior wall myocardial infarction with CAD and for similar levels of
      left ventricular dysfunction, RV systolic function appeared to be more altered in
      IDC.

PMID- 8147307
TI  - A nomogram to predict exercise capacity from a specific activity questionnaire
      and clinical data.
AB  - Recent investigations suggested that clinical exercise testing can be optimized
      by individualizing the protocol, depending on the purpose of the test and the
      subject tested. This requires some knowledge of a patient's exercise capacity
      before beginning the test. The accuracy of a simple physical activity
      questionnaire and readily available clinical data in predicting subsequent
      treadmill performance was examined. A brief, self-administered questionnaire
      (VSAQ) was developed for veterans who were referred to exercise testing for
      clinical reasons. The VSAQ was designed to determine which specific daily
      activities were associated with symptoms of cardiovascular disease (fatigue,
      chest pain and shortness of breath). Two hundred twelve consecutive patients
      (mean age 62 +/- 8 years) referred for maximal exercise testing were studied.
      Clinical and demographic variables were added to VSAQ responses in a stepwise
      regression model to determine their ability to predict treadmill performance.
      Only metabolic equivalents by VSAQ, and age were significant predictors of
      treadmill performance; these 2 variables yielded R = 0.82 (SEE 1.43; p < 0.001),
      and explained 67% of the variance in exercise capacity. The regression equation
      reflecting the relation between age, VSAQ and exercise capacity was: achieved
      metabolic equivalents = 4.7 + 0.97 (VSAQ) - 0.06 (age). Using this equation, a
      nomogram was developed. Incorporating the VSAQ with the nomogram requires only a
      few minutes, and yields a reasonably accurate estimate of a patient's exercise
      capacity. Although the present equation is population-specific, a similar
      approach in different populations may be useful for individualizing protocols for
      clinical exercise testing.

PMID- 8147308
TI  - Comparison of medical care costs between successful radiofrequency catheter
      ablation and surgical ablation of accessory pathways in the pediatric age group.

PMID- 8147309
TI  - Assessment of the diagnostic value of head-up tilt testing in the evaluation of
      syncope in hypertrophic cardiomyopathy.

PMID- 8147311
TI  - Effects of advancing pregnancy on left ventricular function during bicycle
      exercise.

PMID- 8147310
TI  - Prognostic indicators of one-year outcome after cardiomyoplasty for idiopathic
      dilated cardiomyopathy.

PMID- 8147312
TI  - Relation of atrial pressure and plasma level of atrial natriuretic factor in
      cardiac tamponade.

PMID- 8147313
TI  - Left ventricular filling in young normotensive obese adults.

PMID- 8147314
TI  - Valve replacement for tricuspid regurgitation appearing late after healing of
      left ventricular posterior wall and right ventricular acute myocardial
      infarction.

PMID- 8147315
TI  - Frozen yogurt near deep-freeze.

PMID- 8147316
TI  - Chest X-ray and electrocardiographic abnormality after permanent pacemaker
      insertion.

PMID- 8147317
TI  - Progressive pulmonary hypertension after the arterial switch procedure.

PMID- 8147318
TI  - Double right coronary artery.

PMID- 8147319
TI  - The ineffectiveness of a commonly recommended lipid-lowering diet in
      significantly lowering the serum total and low-density lipoprotein cholesterol
      levels.

PMID- 8147320
TI  - Error in published article.

PMID- 8147321
TI  - McCollum Award Lecture, 1993: triglyceride-rich lipoproteins and atherosclerosis-
      new perspectives.

PMID- 8147322
TI  - Determinants of total daily energy expenditure: variability in physical activity.
AB  - Excessive energy intake and/or reduced total daily energy expenditure (TEE)
      causes obesity. To determine the relationship between obesity and TEE in an
      obesity-prone population, we measured TEE, 24-h sedentary energy expenditure
      (SEDEE), and basal metabolic rate (BMR) in 30 Pima Indian men (83.6 +/- 20.0 kg
      and 31 +/- 9% fat) by the doubly labeled water method and a respiratory chamber.
      The energy expenditure for physical activity (EEACT) was calculated as TEE - (BMR
      + 0.1 TEE), where 10% of TEE is an estimate of the thermic effect of food. Fat
      free mass was the best single determinant (P < 0.01) of TEE, explaining 48% of
      its variance. TEE, SEDEE, BMR, and EEACT were 12,010 +/- 2292, 9945 +/- 1559,
      7677 +/- 1901, and 3297 +/- 1732 kJ/d, respectively. Because EEACT is dependent
      on body weight, EEACT/kg body wt (41.7 +/- 23.2 kJ.d-1.kg-1) and TEE/(BMR + 0.1
      TEE) (1.39 +/- 0.22) were used as indexes of the level of physical activity. Both
      indexes correlated negatively with percent body fat (r = -0.56, P < 0.01 and r = 
      0.42, P < 0.03, respectively). These results suggest that obesity is associated
      with lower levels of physical activity.

PMID- 8147323
TI  - Effects of alcohol intake on resting energy expenditure in young women social
      drinkers.
AB  - This investigation evaluated the effects of alcohol consumption, controlled for
      the energy in alcohol and chronic effects of smoking, on resting energy
      expenditure (REE) in college-aged social drinkers. Sixteen women who both smoked
      and drank alcohol were administered, on 4 separate days in a counterbalanced
      order, 1) cigarettes alone, 2) alcohol alone, 3) alcohol plus cigarettes, or 4)
      cigarettes with an energetic control. Each session consisted of a 25-min REE
      baseline, treatment in a randomly assigned order, and a 105-min assessment of
      REE. Analysis indicated that alcohol significantly (P < 0.05) increased REE for
      up to 95 min after ingestion [increases of 29.6-68.4 kJ (124-287 kcal)/24 h],
      increases that could not be accounted for by the energy content of the drink
      alone. Smoking and alcohol together also raised REE above baseline but not more
      than alcohol alone. It was concluded that alcohol intake raises REE, potentially
      explaining why alcohol interferes with energy utilization. Potential implications
      for alcohol intake, nutrition, and weight loss are presented.

PMID- 8147324
TI  - The predictive value of childhood body mass index values for overweight at age 35
      y.
AB  - Larger body mass index values (BMI in kg/m2) are associated with increased
      morbidity and mortality in adulthood and there are significant correlations
      between BMI values in childhood and in adulthood. The present study addresses the
      predictive value of childhood BMI for overweight at 35 +/- 5 y, defined as BMI >
      28 for men and > 26 for women. Analyses of data for 555 white children indicated
      that overweight at 35 y can be predicted from BMI at younger ages. The prediction
      is excellent at age 18 y, good at 13 y, but only moderate at ages younger than 13
      y. For 18-y-olds with a BMI value exceeding the 60th percentile, the odds of
      overweight at 35 y are 34% for men and 37% for women. A clinically applicable
      method is provided to assign an overweight child to a group with a known
      probability of high BMI values in adulthood.

PMID- 8147325
TI  - Lipoprotein response to exercise training and a low-fat diet in older subjects
      with glucose intolerance.
AB  - The purpose of this study was to determine the effect of aerobic exercise
      training (Ex), a low-fat diet (LF, 19% fat), or combined interventions (LF-Ex) on
      lipoprotein cholesterol (LDL, HDL, and VLDL) and triglyceride (TG) concentrations
      in glucose-intolerant subjects while their weight was maintained. Baseline
      dietary fat and carbohydrate composition, body composition, body mass index, age,
      and lipoprotein cholesterol were not different among groups. Aerobic capacity
      increased in both exercise groups (P < 0.01) and remained unchanged in the LF
      group. Body composition was unaltered and change in body weight (kg) was small:
      Ex, -0.8 +/- 0.4, (P < 0.05); LF, +0.4 +/- 0.4; (NS); LF-Ex, -1.4 +/- 0.4 (P <
      0.01). Exercise alone did not significantly affect lipoprotein cholesterol or TG
      concentrations. In LF and LF-Ex, respectively, decreases (P < 0.02) in total
      cholesterol (-0.66 +/- 0.24 and -0.42 +/- 0.21 mmol/L), HDL (-0.14 +/- 0.07 and 
      0.26 +/- 0.04), and LDL (-0.60 +/- 0.25 and -0.23 +/- 0.13) were seen after 12
      wk, whereas VLDL and TG remained unchanged. Our data indicate that beneficial
      effects of exercise training on lipid indexes are not observed in subjects with
      impaired glucose tolerance on either an average US diet or a low-fat diet if
      substantial changes in weight or body composition do not occur.

PMID- 8147326
TI  - Energy balances of healthy Dutch women before and during pregnancy: limited scope
      for metabolic adaptations in pregnancy.
AB  - To investigate changes in energy metabolism during pregnancy, complete 8-d energy
      balances were measured before pregnancy and at 12, 23, and 34 wk gestation in 12
      healthy Dutch women. While for each individual woman experimental diets were kept
      constant throughout the study with average intakes of 8.76 +/- 0.92 MJ/d (before
      pregnancy), 8.72 +/- 1.08 MJ/d (week 12), 8.85 +/- 0.93 MJ/d (week 23), and 8.72
      +/- 1.12 MJ/d (week 34), neither the digestibility nor the metabolizability of
      the supplied diets showed significant changes from before pregnancy (92.8% and
      88.6%, respectively) throughout pregnancy (92.7% and 88.2%, respectively). Twenty
      four-hour energy expenditure (24-h EE) increased significantly from 8.63 +/- 0.80
      MJ/d (before pregnancy) to 8.73 +/- 1.15, 9.08 +/- 1.08, and 9.94 +/- 0.94 MJ/d
      in weeks 12, 23, and 34 of gestation, to the extent predictable from changes in
      resting metabolic rate so that in an experimental setting with physical activity
      and energy intake standardized there seems little scope for other adaptive
      mechanisms.

PMID- 8147327
TI  - Is milk production impaired by dieting during lactation?
AB  - To determine the feasibility of a weight-loss program during lactation, 33
      healthy, well-nourished, breast-feeding women were enrolled. Twenty-two women
      completed the 10-wk study, losing a mean (+/- SD) of 4.8 +/- 1.2 kg. Mean energy
      intake during the study was nearly 2.25 MJ (538 kcal) below the mean daily
      baseline intake of 9.64 +/- 2.48 MJ (2303 +/- 592 kcal). The sum of three
      maternal skinfold thickness, waist, and hip measurements were significantly
      smaller (P = 0.0001) at study completion. Mean daily milk production was 759 +/-
      142 mL/d at baseline and 802 +/- 189 mL/d at week 10. The infants gained an
      average of 21 g/d, or 1.48 +/- 0.40 kg overall. The mean percent fat of milk at
      baseline and 10 wk was 4.06 +/- 2.15 and 4.00 +/- 2.56, respectively. The mean
      daily nitrogen content of milk at baseline and study completion was 1.82 +/- 0.32
      and 1.62 +/- 27 g/L. These findings suggest that modest weight loss by healthy
      breast-feeding women does not adversely affect either quantity or quality of milk
      consumed by their infants.

PMID- 8147328
TI  - Dietary palmitic acid results in lower serum cholesterol than does a lauric
      myristic acid combination in normolipemic humans.
AB  - In a double-blind crossover study, 17 normocholesterolemic male volunteers were
      fed carefully designed whole-food diets in which 5% of energy was exchanged
      between palmitic (16:0) and lauric + myristic acids (12:0 + 14:0) whereas all
      other fatty acids were held constant. Resident males received each diet during
      separate 4-wk periods. The test diets supplied approximately 30% of energy as fat
      and 200 mg cholesterol/d. Compared with the 12:0 + 14:0-rich diet, the 16:0-rich
      diet produced a 9% lower serum cholesterol concentration, reflected primarily by
      a lower (11%) low-density-lipoprotein-cholesterol concentration and, to a lesser
      extent, high-density-lipoprotein cholesterol. No diet-induced changes were noted
      in the cholesterol content of other lipoproteins, nor did exchange of saturated
      fatty acids affect the triglyceride concentration in serum or lipoprotein
      fractions. These data indicate that a dietary 12:0 + 14:0 combination produces a
      higher serum cholesterol concentration than does 16:0 in healthy
      normocholesterolemic young men fed a low-cholesterol diet.

PMID- 8147329
TI  - Plasma lipids and diet of the Mvskoke Indians.
AB  - Plasma lipids, lipoproteins, and apolipoproteins were measured in 123 female and
      57 male Mvskoke Indians, a population of American Indians with a high prevalence
      of non-insulin-dependent diabetes mellitus (NIDDM). Dietary patterns were
      assessed with a food-frequency questionnaire. There were no differences in total
      cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), apolipoproteins A-I or B in female Indians with
      and without diabetes. In males with diabetes, however, LDL-C was lower.
      Triglyceride and fasting plasma glucose were higher in subjects with diabetes.
      Total cholesterol and LDL-C were lower and HDL-C was higher than age and sex
      matched Lipid Research Clinics values, especially for subjects with diabetes.
      This is surprising given that the diet of Mvskoke Indians contains foods high in
      total fat, saturated fatty acids, and cholesterol. We may explain, in part, the
      low incidence of coronary heart disease in this population.

PMID- 8147330
TI  - Sucrose in a lipid-rich meal amplifies the postprandial excursion of serum and
      lipoprotein triglyceride and cholesterol concentrations by decreasing
      triglyceride clearance.
AB  - Nineteen young male normolipidemic volunteers sequentially consumed three test
      meals consisting of cream only, sucrose only, or cream with sucrose. These oral
      fat-tolerance tests showed an amplification of the postprandial excursion of
      serum triglyceride and cholesterol concentrations when sucrose was included in a
      lipid-rich meal compared with both the cream-only meal and the sucrose-only meal.
      The triglyceride concentration increase occurred only in the late postprandial
      phase whereas the cholesterol concentration was increased for the entire 8 h
      studied. The increased triglyceride and cholesterol concentrations in the
      triglyceride-rich lipoprotein (TRL) fraction accounted for most of the increase.
      The clearance of an intravenous lipid emulsion was measured before and 2 and 4 h
      after a sucrose meal. The two postprandial clearance rates were 34% slower than
      the fasting value. These data indicate that sucrose-induced postprandial
      hypertriglyceridemia may be induced by an inhibition of the clearance of
      triglyceride. The slower rate of lipolysis may cause the accumulation of
      cholesterol in TRL.

PMID- 8147331
TI  - Dietary trans fatty acids: effects on plasma lipids and lipoproteins of healthy
      men and women.
AB  - Effects of cis and trans monounsaturated fatty acids (TFA) and saturated fatty
      acids were assessed in 29 men and 29 women consuming controlled diets. Subjects
      ate each diet for 6 wk in a Latin square design. The diets, each with 39-40% of
      energy as fat were: 1) high oleic (16.7% of energy as oleic acid), 2) moderate
      TFA (3.8% of energy as TFA), 3) high TFA (6.6% of energy as TFA), 4) and
      saturated (16.2% of energy as lauric+myristic+palmitic acids). Compared with the
      oleic diet, LDL cholesterol increased 6.0%, 7.8%, and 9.0% after moderate TFA,
      high TFA, and saturated diets, respectively. HDL cholesterol was unchanged after
      moderate TFA, but was slightly lower (2.8%) after high TFA. HDL cholesterol after
      the saturated diet was 3.5% higher than after the oleic diet. Changes in
      apolipoproteins B and A-I corresponded with changes in the lipoprotein
      cholesterols. Thus, compared with oleic acid, dietary TFAs raise LDL cholesterol,
      but to a slightly lesser degree than do saturates, and high TFA concentrations
      may result in minor reductions of HDL cholesterol.

PMID- 8147333
TI  - Comparative study of the acute effects of resistant starch and dietary fibers on
      metabolic indexes in men.
AB  - The effect of ingestion of the same amount (30 g) of a resistant starch (lintner)
      and cellulose on energy expenditure (EE), colonic fermentation (breath-hydrogen
      test), and blood glucose, insulin, and free fatty acid (FFA) concentrations were
      compared in seven healthy volunteers in a first experiment. In a second
      experiment the same indexes were measured in six healthy volunteers after the
      ingestion of diets composed of 50 g glucose alone or mixed with 30 g lintner, or
      cellulose, or pectin. In the first experiment no differences between lintner and
      cellulose were observed on the measured indexes. The notable difference was the
      increased apparent colonic fermentation with lintner after 6 h. In experiment 2,
      although insulin response was significantly lower in the pectin-added diet, the
      results obtained with the four different diets were not significantly different.
      The metabolic characteristics of lintner were closer to cellulose than to pectin.
      In conclusion, the acute effect of the ingestion of a resistant starch (lintner)
      on the measured metabolic indexes is similar to that of a known insoluble fiber-
      cellulose.

PMID- 8147332
TI  - Citrus pectin and cholesterol interact to regulate hepatic cholesterol
      homeostasis and lipoprotein metabolism: a dose-response study in guinea pigs.
AB  - Guinea pigs were fed increasing concentrations of citrus pectin (CP) (0-12.5%,
      wt/wt) with low (LC, 0.04%) or high (HC, 0.25%) cholesterol. Animals fed LC diets
      had reduced plasma LDL concentrations with 10% and 12.5% CP and hepatic membrane
      apolipoprotein B/E receptor expression increased with high dosages of CP. Hepatic
      3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity increased with
      12.5% CP whereas hepatic cholesterol concentrations and acyl-CoA:cholesterol
      acyltransferase (ACAT) activity were not different. In contrast, with HC diets,
      plasma LDL concentrations were reduced in a dose-response manner by 29%, 30%, and
      67% with 7.5%, 10%, and 12.5% CP intake (P < 0.001) and apolipoprotein B/E
      receptor number was increased and inversely correlated with plasma LDL in the HC
      group (r = -0.81, P < 0.005). Animals fed HC diets had a dose-dependent decrease
      in hepatic cholesterol and ACAT activity, with intake of 12.5% CP having the
      major effect. Hepatic HMG-CoA reductase activity was suppressed by HC diets and
      only intake of 12.5% CP reversed this suppression. The most significant effects
      of CP on hepatic cholesterol, enzymes of hepatic cholesterol homeostasis, and the
      apolipoprotein B/E receptor were in animals fed the HC diets. These metabolic
      alterations partially explain the reduced plasma LDL of guinea pigs fed large
      amounts of CP.

PMID- 8147334
TI  - Effects of beta-carotene supplementation on lipid peroxidation in humans.
AB  - The ability of beta-carotene (BC) to reduce lipid peroxidation in humans was
      investigated. In this randomized double-blind controlled trial, 42 nonsmokers and
      28 smokers received either 20 mg BC or placebo daily for 4 wk. Twenty-five
      smokers and 38 nonsmokers completed the trial. Changes in plasma BC
      concentrations increased significantly (P < 0.0005) and to the same extent in
      both groups supplemented with BC. There were no significant changes among the
      placebo groups. At baseline, lipid peroxidation measured by breath-pentane output
      (BPO) was significantly higher in the two smoking groups (BC: 8.8 +/- 1.1,
      placebo: 9.4 +/- 1.4 pmol.kg-1.min-1) than in the two nonsmoking groups (BC: 5.7
      +/- 0.5, placebo: 5.9 +/- 0.6 pmol.kg-1.min-1) (P < 0.005). BPO decreased
      significantly only in smokers receiving BC (6.5 +/- 0.7 pmol.kg-1.min-1) (P <
      0.04). Changes in breath-ethane output were not significant. Therefore, lipid
      peroxidation measured by BPO is significantly higher in smokers than in
      nonsmokers and is reduced by BC supplementation in smokers. There was no
      significant change (95% CI - 1.26, 1.12) in BPO when nonsmokers received BC.

PMID- 8147335
TI  - Effect of smoking on serum nutrient concentrations in African-American women.
AB  - The relationship between current cigarette smoking and serum concentrations of
      vitamins C, E, and A, and of five carotenoids in human serum were examined in 91
      low-income, African-American women. General linear models were used to adjust
      geometric mean serum concentrations of micronutrients for age, dietary and
      supplement intakes, total energy intake, alcohol intake, medication use, body
      mass index, and serum concentrations of cholesterol and triglycerides. Among
      smokers, serum concentrations of alpha-carotene, beta-carotene, cryptoxanthin,
      and lycopene averaged only 71-79% of the concentrations among nonsmokers. Mean
      serum concentrations of vitamins C and E and lutein/zeaxanthin were only slightly
      lower among smokers relative to nonsmokers, and current smokers had higher serum
      concentrations of vitamin A. Among current smokers, mean serum concentrations of
      all five carotenoids decreased with an increase in the amount smoked. The
      negative effect of smoking on serum concentrations of antioxidant carotenoids may
      pose a serious health risk in low-income populations already at higher risk for
      many chronic diseases.

PMID- 8147336
TI  - Plasma carotenoid concentrations before and after supplementation with a
      carotenoid mixture.
AB  - Plasma carotenoid concentrations were determined by HPLC in 11 individuals
      consuming low-carotenoid diets and after taking a carotenoid supplement. Subjects
      first consumed low-carotenoid diets for 2 wk, then supplemented these diets daily
      with 8.5 mg beta-carotene, 3.5 mg alpha-carotene, and 0.5 mg lycopene, from
      natural sources for 4 wk. Serum cholesterol, triglycerides, and lipoproteins were
      determined before and after supplementation. After 2 wk on the low-carotenoid
      diet, plasma concentrations of the three carotenoids fell to approximately 60% of
      baseline values. One week after supplementation, alpha- and beta-carotene
      concentrations returned to baseline and by the end of the supplementation period
      they were significantly higher than baseline values (P < 0.05). Lycopene
      concentrations increased only slightly. Serum lipids did not change
      significantly. Overall, plasma concentrations of these carotenoids reflect the
      amount provided by the supplement. This is the first study reporting increments
      of serum carotenoids, other than beta-carotene, after supplementation.

PMID- 8147337
TI  - Impact of increasing calcium in the diet on nutrient consumption, plasma lipids,
      and lipoproteins in humans.
AB  - This study examined the feasibility of increasing food-derived calcium to 1500
      mg/d and the impact of this change on plasma lipids and nutrient consumption in
      hypertensive (n = 130) and normotensive (n = 196) participants. Three
      interventions were applied in a randomized, parallel, placebo-controlled fashion:
      1) counseling to increase dietary calcium through food consumption to 1500 mg/d
      (n = 106), 2) a 1000-mg/d calcium supplement (n = 109), or 3) placebo (n = 111).
      Plasma lipids were measured before and after 12 wk of intervention whereas
      nutrient intake was monitored throughout the study. At baseline, hypertensive
      patients reported lower intakes of carbohydrates, calcium, magnesium, phosphorus,
      potassium, iron, vitamin D, thiamin, and riboflavin (all P < 0.05). They also had
      lower HDL (P = 0.014) and higher LDL (P < 0.05) compared with normotensive
      subjects. During intervention, calcium, magnesium, phosphorus, potassium,
      thiamin, riboflavin, and vitamins C and D increased (P < 0.01) in the group
      receiving food calcium but not in the placebo or supplement groups. No changes
      occurred in plasma lipids or lipoproteins after 12 wk of intervention.

PMID- 8147338
TI  - Functional consequences of iron supplementation in iron-deficient female cotton
      mill workers in Beijing, China.
AB  - Eighty iron-deficient, nonpregnant female workers were randomly assigned to
      ferrous sulphate (60 or 120 mg Fe/d) or placebo treatment for 12 wk. Energy
      expenditure was estimated during 3 d by heart rate (HR) recording. Production
      efficiency (PE) was calculated as the ratio of productivity to energy
      expenditure. In the iron-treated group mean hemoglobin (Hb) increased from 114 to
      127 g/L (P < 0.001), mean serum ferritin increased from 9.7 to 30.0 micrograms/L
      (P < 0.001), and mean free erythrocyte protoporphyrin decreased from 1.01 to 0.49
      mumol/L (P < 0.001). Mean HR at work decreased from 95.5 to 91.1 beats/min (P <
      0.001), which was inversely correlated with the change in Hb (r = -0.60, P <
      0.001). PE increased significantly in the iron-treated group (P < 0.001) and its
      change paralleled the change in Hb (r = 0.58, P < 0.001). The results show that
      iron supplementation enabled these women to do the same work at a lower energy
      cost.

PMID- 8147339
TI  - Antibody response against tetanus toxoid is enhanced by lipopolysaccharide or
      tumor necrosis factor-alpha in vitamin A-sufficient and deficient rats.
AB  - Reduced antibody response to tetanus toxoid (TT) was previously demonstrated
      during vitamin A deficiency but the response to bacterial lipopolysaccharide
      (LPS) was normal. We addressed whether anti-TT IgG responses are enhanced in
      vitamin A-sufficient and deficient rats by immunization with LPS plus TT.
      Antibody responses in vitamin A-sufficient and deficient rats increased
      significantly after coimmunization (LPS + TT) compared with the response of rats
      immunized with TT alone. In additional studies, recombinant tumor necrosis factor
      alpha (TNF-alpha) also significantly increased the anti-TT IgG concentrations.
      Because pretreatment with anti-TNF before coimmunization or immunization with TT
      alone markedly reduced the anti-TT IgG responses, we infer TNF to be a mediator
      of both the adjuvanticity of LPS and the unstimulated response to TT. In
      conclusion, vitamin A-deficient rats can be stimulated to respond to TT by
      coimmunization with LPS or by treatment with TNF.

PMID- 8147340
TI  - Cholesterol-lowering and blood pressure effects of immune milk.
AB  - The plasma cholesterol-lowering and blood pressure effects of a skim milk powder
      (immune milk) produced from dairy cows hyperimmunized with a multivalent
      bacterial vaccine were assessed in a double-blind crossover study of
      hypercholesterolemic subjects who consumed daily 90 g immune milk or a normal
      product. There was a significant reduction in plasma total and LDL cholesterol of
      5.2% (95% CI 2.5, 7.9) and 7.4% (95% CI 4.1, 10.7), respectively, with 10 wk of
      immune milk consumption compared with control, but no change in HDL cholesterol
      or triglycerides. A significant systolic and diastolic blood pressure-lowering
      effect (5 and 4 mm Hg, respectively) was also demonstrated. Thus, immune milk may
      be a useful adjunct in the dietary management of hypercholesterolemia and the
      mechanisms of its cholesterol-lowering and blood pressure effects warrant further
      study.

PMID- 8147341
TI  - Low-fat, high-fiber diet favorably affects several independent risk markers of
      ischemic heart disease: observations on blood lipids, coagulation, and
      fibrinolysis from a trial of middle-aged Danes.
AB  - We served a low-fat (28% of energy), high-fiber (3.3 g/MJ) diet according to
      Nordic nutrition recommendations (Rec diet), and a high-fat diet (39% of energy)
      corresponding to the average Danish diet (Dane diet) for periods of 2 wk in a
      randomized crossover study of 21 healthy middle-aged individuals. The Rec diet
      resulted in lower serum concentrations of low-density-lipoprotein (LDL)
      cholesterol (medians: 2.77 vs 3.04 mmol/L, P < 0.001) and high-density
      lipoprotein (HDL) cholesterol (1.08 vs 1.24 mmol/L, P < 0.001), and higher
      fasting triglycerides (1.11 vs 0.86 mmol/L, P = 0.04) than did the Dane diet.
      Furthermore, the Rec diet lowered plasma factor VII coagulant activity (FVIIc)
      (88% vs 96%, P = 0.002) and raised plasma fibrinolytic activity. Our observations
      indicate that a low-fat, high-fiber diet may not only reduce the atherogenic but
      also the thrombogenic tendency of an individual compared with a diet
      corresponding to the average Danish diet.

PMID- 8147342
TI  - Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early
      onset coronary artery disease.
AB  - High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary
      artery disease (CAD). Folate and vitamin B-12 are required for the primary
      metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and
      these two vitamin cofactors were investigated in a case-control study of 101
      white males aged 30-50 y with angiographically demonstrated CAD, and 108 white
      male, similarly aged, control subjects living in the same community as the
      patients. The odds ratio (OR) of CAD per quartile increase of plasma Hcy
      concentration based on control values was 1.6 (95% CI: 1.3, 2.1). After age, HDL
      and LDL cholesterol, body mass index, smoking, hypertension, and diabetes were
      controlled for, Hcy remained an independent risk factor (OR: 1.4; 95% CI: 1.0,
      2.0). The OR change per quartile increase of folate concentration was 0.8 (95%
      CI: 0.6, 1.0). This difference was reduced (OR: 0.9; 95% CI: 0.7, 1.2) after Hcy
      adjustment. No difference in the geometric mean of vitamin B-12 concentration was
      found between patients and control subjects, both 5.8 nmol/L. However, after Hcy
      and the other CAD risk factors were controlled for, the OR per quartile increase
      in vitamin B-12 concentration was 1.5 (95% CI: 1.0, 1.8). Reduction in plasma Hcy
      by interventions to increase plasma folate concentration may decrease CAD risk.

PMID- 8147343
TI  - Dietary diversity and health.

PMID- 8147344
TI  - The patient-doctor relationship.

PMID- 8147345
TI  - Evolution of concepts regarding Helicobacter pylori: from a cause of gastritis to
      a public health problem.

PMID- 8147346
TI  - Delivering bad news in gastroenterology.

PMID- 8147347
TI  - Liver transplantation in children.

PMID- 8147348
TI  - Diagnosis of chronic hepatitis C: comparison of immunoassays and the polymerase
      chain reaction.
AB  - We evaluated a series of first- and second-generation enzyme-linked immunoassays
      for anti-HCV and compared the findings to those with two confirmatory assays, the
      recombinant immunoblot assay and serum HCV RNA, in patients with chronic
      hepatitis C, primary biliary cirrhosis, and chronic hepatitis B. All second
      generation immunoassays had good sensitivities (98-100%). Interestingly,
      detection of HCV RNA had a sensitivity of only 93%, although it was 100%
      specific. The recombinant immunoblot assay and a peptide-based immunoassay also
      had good specificity (97% and 100%, respectively), whereas the second-generation
      immunoassay based on recombinant proteins had a high rate of false positivity,
      particularly among patients with primary biliary cirrhosis and hyperglobulinemia
      (specificity 68%). Thus, the diagnosis of HCV infection appears to require the
      use of more than one test. Whereas a second-generation enzyme-linked immunoassay
      can be used as an initial test, a confirmatory test (such as recombinant
      immunoblot assay or determination of hepatitis C viral RNA) may be required if
      the diagnosis remains uncertain.

PMID- 8147349
TI  - Are esophageal symptoms reflux-related? A study of different scoring systems in a
      cohort of patients with heartburn.
AB  - OBJECTIVE: To assess three different methods of correlating symptoms with
      episodes of acid reflux in gastroesophageal reflux disease. METHODS: One hundred
      and one consecutive patients with heartburn were recruited. Patients were divided
      into those with and those without endoscopic esophagitis. Three different symptom
      indices were used, one of which was based on the binomial formula. It took into
      account not only the ratio of acid-related symptoms to all symptoms, but also the
      quantity of acid reflux. RESULTS: There was complete agreement between all three
      indices in 78% of the patients. All three indices were positive significantly
      more often (p < 0.001) in patients with esophagitis than in patients with no
      esophagitis. CONCLUSIONS: All indices gave similar results. The binomial symptom
      index offers theoretical advantages, but a prospective study of response to acid
      suppression would be required to evaluate further its merits.

PMID- 8147350
TI  - Globus pharyngis, commonly associated with esophageal motility disorders.
AB  - OBJECTIVES: To evaluate the role of gastrointestinal and psychiatric etiology in
      globus sensation. METHODS: The study population consisted of 32 consecutive
      patients with globus sensation without dysphagia referred to the Department of
      Otorhinolaryngology in Helsinki University Hospital. Eleven patients were
      excluded from the study: two because of advanced age, one prisoner, and six
      patients refused further studies. Only two patients (6%) were found to have
      abnormal otorhinolaryngological status. These patients were also excluded from
      the study. Esophagogastroduodenoscopy, 24-h pH recording, esophageal manometry,
      and Bernstein acid perfusion test were carried out in 21 patients (13 females,
      eight males, mean age 49 yr). Psychiatric evaluation was done in 20 patients; one
      patient refused the psychiatric consultation. RESULTS: Abnormal endoscopy was
      found in 12/21 (57%) of the patients, with antral gastritis and hiatal hernia
      being the most common findings. Two patients had esophagitis. Sixty-seven percent
      demonstrated abnormalities in esophageal manometry, the most frequent finding
      being a nonspecific esophageal motility disorder (29%). pH monitoring was normal
      in 16/21 of patients (76%), whereas the Bernstein test showed positive results in
      13/21 (62%). With DSM IIIR as the diagnostic tool, five of 20 patients (25%)
      received a psychiatric diagnosis. CONCLUSIONS: Globus sensation has a multiple
      etiology, and local reasons are rare but should first be ruled out. Abnormalities
      in esophageal motility are commonly found, and these patients seem to be
      sensitive to esophageal acidity. Esophageal manometry and ambulatory 24-h pH
      recording should be included in the evaluation of a globus patient. The number of
      psychiatric disorders does not differ from that in the general population.
      Treatment of globus sensation should be directed toward the abnormality found
      behind the symptom.

PMID- 8147351
TI  - The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis
      of erosive mucosal damage.
AB  - OBJECTIVES: The primary objective of the present investigation was to determine
      from variables obtained from 24-h esophageal pH monitoring significant
      discriminators between patients with and without erosive esophageal mucosal
      damage. METHODS: Data obtained from this study were from 24-h esophageal pH
      monitoring and the results of upper gastrointestinal endoscopy. Statistical
      methods included the use of multivariate discriminant analysis. RESULTS: The
      results revealed that the single best measure which discriminated patients with
      erosive and nonerosive esophagitis was the number of recumbent reflux episodes
      lasting greater than 5 min. CONCLUSIONS: We conclude from these data that 1)
      specific evaluation of recumbent reflux and acid exposure can add substantially
      to the interpretation of 24-h esophageal pH studies, particularly with regard to
      identifying patients at risk for the development of erosive esophagitis or other
      potential complications; 2) esophageal mucosal erosions are associated with an
      increase in percent acid contact time in both the upright and supine positions,
      but the pattern of reflux, particularly during the nocturnal interval in terms of
      the number of episodes greater than 5 min, adds significant predictive value in
      discriminating patients with erosive mucosal damage.

PMID- 8147352
TI  - Antimycobacterial therapy in Crohn's disease: results of a controlled, double
      blind trial with a multiple antibiotic regimen.
AB  - Several recent reports have suggested an association of atypical mycobacteria
      with Crohn's disease. OBJECTIVES: The goal of this double-blind, placebo
      controlled trial was to determine the efficacy of treatment with
      antimycobacterial drugs in maintaining clinical remission and in reducing active
      inflammatory lesions. METHODS: Forty patients (15 male) with refractory, steroid
      dependent Crohn's disease were randomized to receive 2 months of tapering
      steroids plus either a 9-month regimen of ethambutol, clofazimine, dapsone and 1
      day dose only of rifampicin (n = 22), or identical placebo. RESULTS: Three
      patients (two on active drug) were unable to discontinue steroids, and one
      patient on active drug was withdrawn for side effects during the first 2 months.
      Three of the remaining 19 patients on active drug relapsed during the study
      period, compared with 11 of 17 on placebo (log likelihood ratio = 4.6; p = 0.03).
      Another patient was withdrawn in remission at 5 months for anemia related to
      dapsone. Nine patients whose disease relapsed or persisted on placebo were
      crossed over to active drug; five achieved sustained remission, two failed, and
      two were withdrawn for side effects. Substantial endoscopic or radiologic healing
      did not occur. CONCLUSION: This study suggests that the treatment regimen with
      rifampicin, ethambutol, clofazimine, and dapsone is effective in relief of
      symptoms and maintenance of remission in some Crohn's disease patients.

PMID- 8147353
TI  - Epidemiology, clinical manifestations, and outcome of Clostridium difficile
      associated diarrhea.
AB  - OBJECTIVE: Clostridium difficile gastrointestinal disease is an important
      nosocomial infection and is associated with recent antibiotic use. This study
      evaluated C. difficile-associated diarrhea (CDAD) over a 2-yr period. METHODS:
      All 60 patients with C. difficile enterotoxin in their stools, and diarrhea, were
      retrospectively analyzed at a 615-bed teaching hospital. Institution antibiotic
      usage and discharge medical diagnoses were correlated with the study patients.
      RESULTS: Thirty-eight study patients (53%) had major or extreme admitting
      symptoms. Only four (7%) had no co-morbid illness. The incidence of CDAD
      increased significantly (p < 0.05) after 4 wk of hospitalization. No demographic
      or temporal clustering was discovered. Leukocytosis (60%), leftward
      polymorphonuclear shift (47%), dehydration (30%), weight loss (23%), and oliguria
      (12%) were the major clinical findings. Among these subject 51 (85%) had been on
      ceftriaxone and/or ceftazidime in the preceding 6 wk; ceftriaxone/ceftazidime was
      highly significantly associated (p < 0.01) with more cases than expected by usage
      alone. No patient on ticarcillin/clavulanate developed CDAD, although it was the
      most commonly used antibiotic (p < 0.00001). Higher mortality was associated with
      older debilitated nursing home residents. CONCLUSIONS: Third-generation
      cephalosporin use correlated with the development of CDAD;
      ticarcillin/clavulanate usage did not. Morbidity and mortality associated with
      CDAD is significant, is worse in debilitated older nursing home patients, and is
      more likely to occur in hospitalizations lasting longer than 4 wk.

PMID- 8147354
TI  - Smoking, alcohol, and nonsteroidal anti-inflammatory drugs in outpatients with
      functional dyspepsia and among dyspepsia subgroups.
AB  - OBJECTIVE: Although there is a paucity of data, environmental factors such as
      smoking, alcohol, and non-steroidal anti-inflammatory drugs (NSAIDs) are believed
      to be important in the pathogenesis of functional dyspepsia. We aimed to
      evaluate, in outpatients presenting for endoscopy, the role of environmental
      factors in functional dyspepsia. METHODS: A consecutive sample of 73 patients
      with functional dyspepsia completed a validated questionnaire prior to endoscopy.
      The comparison group consisted of outpatients attending for endoscopy who did not
      have functional dyspepsia (n = 658). Logistic regression analysis was used to
      estimate the association between functional dyspepsia and potential risk factors
      adjusting for age, gender, socioeconomic status, general health, and irritable
      bowel syndrome. RESULTS: Smoking, alcohol, aspirin, non-aspirin NSAIDs, and
      acetaminophen were not associated with functional dyspepsia. Patients were
      significantly less likely to have functional dyspepsia if they were current or
      past smokers, and there was a trend for patients to be less likely to have
      functional dyspepsia if they took NSAIDs regularly. When patients with functional
      dyspepsia were classified into symptom subgroups, the environmental factors were
      not found to be associated with ulcer-like dyspepsia (vs. nonspecific dyspepsia
      or organic disease). CONCLUSIONS: Smoking, alcohol, and NSAIDs are not associated
      with an increased risk of functional dyspepsia in outpatients presenting for
      endoscopy.

PMID- 8147355
TI  - Helicobacter pylori reinfection rate, in patients with cured duodenal ulcer.
AB  - OBJECTIVE: To determine the reinfection rate of the gastric mucosa in patients
      previously cured of duodenal ulcers, following the eradication of Helicobacter
      pylori. Only those remaining H. pylori-negative beyond 12 months of follow-up
      were studied, to minimize the potential inclusion of patients with H. pylori
      recrudescence. METHODS: Patients with endoscopically proven duodenal ulcers who
      had been treated with triple therapy, resulting in documented eradication of H.
      pylori and cure of the ulcer for at least 4 years, were recalled and had their H.
      pylori status determined by the 14C-urea breath test. Those found positive for H.
      pylori underwent endoscopic confirmation of the infection. RESULTS: Of the 94
      patients restudied, with a follow-up period range of 48-96 months or a total of
      549.8 yr, only two (2.2%) were again H. pylori positive. This gives an effective
      reinfection rate of 0.36% per patient year. In the two H. pylori-positive
      patients, one had normal mucosa endoscopically, whereas duodenitis without active
      ulceration was present in the other. The former was asymptomatic, whereas the
      latter patient was using ranitidine daily for symptom control. CONCLUSION: In the
      Australian setting, following cure of duodenal ulcer disease by eradication of H.
      pylori, subsequent reinfection is an unusual phenomenon. We conclude that efforts
      aimed at eradication of H. pylori in duodenal ulcer are justified and are
      worthwhile.

PMID- 8147356
TI  - Vitamin C concentration in gastric juice before and after anti-Helicobacter
      pylori treatment.
AB  - OBJECTIVES: To investigate the change of vitamin C concentration (ascorbic and
      dehydroascorbic acid) in gastric juice after anti-Helicobacter pylori treatment,
      and to relate any observed change to gastric pH, inflammatory compromise of the
      gastric mucosa, plasma vitamin C concentration, and smoking habits. METHODS:
      Plasma and gastric juice vitamin C, fasting gastric juice pH, gastric histology,
      and smoking status were studied in 70 patients with H. pylori-associated
      gastritis before and after therapy. RESULTS: Gastric juice ascorbic acid
      increased significantly after H. pylori clearance. For the most part, this change
      was confined to patients who experienced reduction of gastric pH. It was also
      related to improvement of the compromise of the gastric epithelium, reduction of
      the proportion of vitamin C composed by dehydroascorbic acid, and increase of the
      gastric juice/plasma vitamin C concentration gradient. Smokers had lower vitamin
      C concentrations in plasma and gastric juice before and after H. pylori clearance
      than nonsmokers. CONCLUSIONS: The findings are consistent with a causal
      association between H. pylori infection and low ascorbic acid levels in gastric
      juice, and support two mechanisms for this association: increased oxidation and a
      decreased secretion of ascorbic acid.

PMID- 8147357
TI  - Predominantly gastrointestinal symptoms and signs in 11 consecutive AIDS patients
      with gastrointestinal lymphoma: a multicenter, multiyear study including 763 HIV
      seropositive patients.
AB  - OBJECTIVES: Gastrointestinal lymphoma is a distinct subgroup of lymphoma in HIV
      seronegative patients. This study analyzes whether gastrointestinal lymphoma
      similarly forms a distinct clinical subgroup in HIV-seropositive patients.
      METHODS: Case control study of medical records of 763 human immunodeficiency
      virus-seropositive patients admitted to three university hospitals from 1986
      through 1992, including 22 with non-Hodgkin's lymphoma. Eleven patients (50%) had
      gastrointestinal lymphoma, and 11 controls had extraintestinal lymphoma. RESULTS:
      The clinical presentation in patients with gastrointestinal lymphoma was
      dominated by gastrointestinal symptoms and signs and gastrointestinal
      complications. Common symptoms and signs included: change in bowel habits, gross
      or occult blood per rectum, involuntary weight loss, abdominal pain, abdominal
      tenderness, peripheral lymphadenopathy, cachexia, and hepatosplenomegaly.
      Significant gastrointestinal complications during the presenting admission
      included gastrointestinal bleeding in five, intestinal obstruction in one, and
      dysphagia from an esophageal stricture in one. Subsequent complications included
      a walled-off perforating gastric ulcer in one and obstructive jaundice in one. In
      contrast, the control patients with extraintestinal lymphoma had significantly
      fewer gastrointestinal symptoms and gastrointestinal complications (p < 0.001 and
      p < 0.01, respectively, Fisher's exact test). Upper gastrointestinal series or
      barium enema identified lymphomatous gastrointestinal lesions in all seven
      patients undergoing these tests. The pathologic diagnosis was made from
      endoscopic biopsies in six of six patients undergoing panendoscopy, and two of
      three patients undergoing lower endoscopy. Tumor sites included stomach in six,
      colon in three, ileum in two, esophagus in two, and duodenum in one. Eight
      patients had extraintestinal lesions at diagnosis, including four with
      extraabdominal extranodal lesions. The outcome of gastrointestinal lymphoma was
      poor with all therapies (mean combined survival = 3.6 +/- 2.2 months), and was
      not significantly different from that for the controls (mean survival = 4.1 +/-
      2.7 months, Student's t test). CONCLUSIONS: This study suggests that
      gastrointestinal lymphoma in AIDS shares the poor prognosis and aggressive
      features of extraintestinal lymphoma in AIDS, but has unique localizing features
      at presentation of predominantly gastrointestinal symptoms and signs, and
      frequent gastrointestinal complications.

PMID- 8147358
TI  - Effect of erythromycin on gastric and gallbladder emptying and gastrointestinal
      symptoms in scleroderma patients is maintained medium term.
AB  - OBJECTIVES: Scleroderma patients frequently present esophageal and gastric
      emptying abnormalities and small bowel dysfunction. Erythromycin, a macrolide
      antibiotic, has been found to accelerate gastric and gallbladder emptying in both
      healthy subjects and diabetic patients. Our objective was to investigate the
      effects of 4-wk oral erythromycin administration on the gastric and gallbladder
      emptying, gastrointestinal symptoms (early satiety, abdominal pain, nausea,
      bloating, vomiting, and constipation), and motilin plasma levels of patients with
      scleroderma. METHODS: 12 scleroderma patients were investigated before and after
      4-wk treatment with 250 mg oral erythromycin three times a day. The effect of a
      single i.v. dose of 2 mg/kg/h erythromycin on gastric and gallbladder emptying
      before starting the oral treatment was also evaluated. Gastric and gallbladder
      emptying after a solid meal were evaluated by sonography. RESULTS: Single i.v.
      administration of erythromycin before the meal reduced gastric emptying T1/2 from
      121.3 +/- 14.0 to 45.5 +/- 7.3 min (p < 0.01) and accelerated gallbladder
      emptying without affecting the peak. Four-week oral administration of
      erythromycin reduced gastric emptying T1/2 from 121.3 +/- 14.0 min to 46.5 +/-
      8.3 min (p < 0.01). Peak gallbladder emptying was also significantly accelerated,
      while total emptying remained unchanged (p < 0.01). Furthermore, 4-wk
      erythromycin administration reduced both motilin plasma levels (from 223.4 +/-
      53.8 to 145.4 +/- 67.2 pmol/L, p < 0.01) and symptoms of nausea, vomiting, and
      abdominal pain (p < 0.01), and increased bowel movements in a subset of
      scleroderma patients with intestinal pseudo-obstruction. CONCLUSIONS:
      Erythromycin stimulates gastrointestinal motility in patients with scleroderma.
      Administered medium-term, it accelerates gastric and gallbladder emptying and
      alleviates gastrointestinal symptoms.

PMID- 8147359
TI  - Complete colonoscopy: how often? And if not, why not?
AB  - OBJECTIVE: Colonoscopy completion rate is an easily measurable criterion of
      technical competency. Reporting of completion rates lacks uniformity, however,
      and few studies focus on colonoscopy completion alone. The purpose of this study
      is to establish criteria for consistency in the reporting of completion rates, so
      that colonoscopists are better able to use such reports to evaluate their own
      experience. METHODS: A prospective study of colonoscopy completion rate and
      reasons for incompletion was carried out for 2907 patients. Completion was
      defined as the colonoscope touching the end of the colon. Rates are reported as
      crude (all cases) and adjusted (excluding incompletions due to stool and
      disease). RESULTS: The crude completion rate was 93.6% and the adjusted rate was
      98.8%. Reasons for incompletion were stool (n = 47), colonic disease (n = 97),
      and pain or tortuosity (n = 34). The crude completion rate was lower in women
      than in men (92.4% vs. 94.8%), lower in the very young (< 20 yr, 85.7%) and very
      old (> 80 yr, 88.9%), was < 90% in patients presenting with altered bowel habit,
      diarrhea, constipation, hemorrhage, inflammatory bowel disease, abdominal pain,
      or cancer, was only 53.8% in patients in intensive care units, was 84.1% in the
      author's first 127 cases, was lower in women post hysterectomy (92.8% vs. 98.3%),
      and was higher in patients who had had a colon resection [98.4% (right
      colectomy), 99.2% (left colectomy), 95.8% (intact colon)]. When adjusted rates
      were compared, most of those differences disappeared (except male vs. female,
      hysterectomy vs. no hysterectomy). CONCLUSIONS: Crude colonoscopy completion
      rates are affected by a number of factors that may make comparisons between
      colonoscopists difficult. The use of adjusted completion rates minimizes the
      effect of disease-related factors, allows completion rate to be a better
      reflection of technical ability, and may facilitate more uniform reporting of
      colonoscopy results.

PMID- 8147360
TI  - All lactase preparations are not the same: results of a prospective, randomized,
      placebo-controlled trial.
AB  - OBJECTIVE: To compare the efficacy of three commercially available oral lactase
      preparations in adults with lactose intolerance. METHODS: Design--Prospective,
      randomized, placebo-controlled trial. Setting--Outpatient study in a General
      Clinical Research Center. Subjects--Ten lactose-intolerant healthy volunteers
      were challenged with ice cream containing 18 g of lactose. Lactase or placebo was
      given immediately prior to challenge. Measurements--Symptoms and breath hydrogen
      excretion were recorded for 3 h following lactose challenge. RESULTS: The three
      products differed in their abilities to influence symptoms and breath hydrogen
      excretion. Only Lactaid reduced the breath hydrogen excretion with lactose (mean
      peak, area under the curve and cumulative breath hydrogen excretion) (p < 0.05).
      Lactrase and Dairy Ease influenced symptoms: Lactrase reduced pain, bloating and
      total symptomatic scores (p < 0.05), whereas Dairy Ease only reduced pain (p <
      0.05). Lactaid administration did not reduce symptoms. CONCLUSION: In lactose
      intolerant subjects, the available lactase preparations differ in their ability
      to improve both breath hydrogen excretion and symptoms. Lactrase may be the
      product of choice for achieving symptomatic improvement.

PMID- 8147361
TI  - Risk factors for delayed healing of duodenal ulcers treated with famotidine and
      ranitidine.
AB  - OBJECTIVES: 1) To validate risk factors for delayed healing of duodenal ulcers
      identified previously in a pilot study, and 2) To evaluate whether famotidine
      improves the rate of duodenal ulcer healing and pain relief, compared with
      ranitidine. METHODS:  DESIGN: prospective, multicenter, double-observer-blinded,
      randomized trial. SETTING: 594 patients with active duodenal ulcers seen in
      private practice offices, university based medical practices and Veterans Affairs
      hospital clinics. INTERVENTIONS: Patients were randomly assigned to receive
      famotidine 40 mg or ranitidine 300 mg qhs. MEASUREMENTS: Endoscopy was performed
      at entry and at 2, 4, and 8 wk after therapy or until complete ulcer healing.
      Seventeen patient variables, including demographic, past historical, presenting
      historical and endoscopic characteristics, were assessed for their relationship
      to healing. RESULTS: After 4 wk of treatment, by a "per protocol" analysis, three
      risk factors for nonhealing were statistically significant: prior ulcer history
      [63.0% healed, compared to 77.9% with no history, p = 0.001, odds ratio for not
      healing (OR) = 2.1, 95% CI = 1.4-3.1]; ulcer size (61.6% of ulcers > or = 10 mm
      healed at 4 wk compared to 75.5% of smaller ulcers, p = 0.001, OR = 1.9, 95% CI =
      1.3-2.8); and smoking (62% of smokers healed vs. 77.7% of nonsmokers, OR = 2.1,
      95% CI = 1.4-3.1). The presence of multiple risk factors resulted in additive
      risk: for patients with no risk factors, 86.8% healed at 4 wk, with any one risk
      factor 76.8% healed, with two factors 63.0%, and with all three risk factors only
      46.9% healed. Multiple risk factors also affected healing rates at 8 wk.
      Bleeding, alcohol use, and prior NSAID use did not influence ulcer healing.
      Although famotidine resulted in statistically significant faster ulcer healing
      when examined on an "intention-to-treat" basis, there were no differences between
      the drugs when examined on a "per protocol" basis. Patients treated with
      famotidine achieved more rapid pain relief than those treated with ranitidine.
      CONCLUSIONS: 1) Smoking, prior ulcer history, and ulcer size > or = 10 mm exert
      independent risks for nonhealing of duodenal ulcers; 2) These risks are similar
      for both famotidine and ranitidine; 3) Patients with multiple risk factors for
      nonhealing may require more prolonged acid suppression therapy than patients who
      have no risks.

PMID- 8147362
TI  - Interrelationship between esophageal challenge with mechanical and chemical
      stimuli and salivary protective mechanisms.
AB  - Using our newly developed model of esophageal perfusion in humans, we were able
      to study the esophagosalivary reflex in 20 healthy volunteers (12M, 8F; mean age
      40 yr). The placement of the intraesophageal catheter resulted in a 6.3-fold
      increase in the salivation rate over the baseline value (2.27 +/- 0.28 vs. 0.36
      +/- 0.06 ml/min; p = 0.02), whereas inflation of the catheter balloons evoked a
      6.9-fold increase (2.52 +/- 0.21; p < 0.001) in the rate of salivation. A
      stepwise and significant decline of salivation (p = 0.02), observed during
      subsequent perfusion with NaCl was prevented when perfusion with HCl and
      HCl/pepsin solutions was implemented. The placement of the intraesophageal
      catheter resulted in a significant increase of salivary pH over its basal value
      (7.77 +/- 0.05 vs. 6.89 +/- 0.11; p < 0.001). A gradual decline of salivary pH
      during subsequent perfusion with NaCl was eliminated when saline was replaced
      with HCl or HCl/pepsin (7.76 +/- 0.04 vs. 7.46 +/- 0.09; p < 0.01).
      Intraesophageal tubing enormously potentiated the viscosity of saliva (44.50 +/-
      9.0 vs. 9.3 +/- 1.0 mPa.s; p < 0.001). A subsequent decline of viscosity during
      continuous perfusion with saline was also prevented when HCl was substituted for
      NaCl (29.95 +/- 4.5 vs. 19.50 +/- 3.30; p < 0.05). A significant potentiation of
      salivary volume, viscosity, and pH during esophageal stimulation of mechano- and
      chemoreceptors may suggest a contributing role of the esophagosalivary reflex in
      the maintenance of the esophageal mucosal integrity under the impact
      gastroesophageal reflux.

PMID- 8147363
TI  - Impact of acid and pepsin on human esophageal prostaglandins.
AB  - OBJECTIVES: Although the prostaglandin-mediated mucosal protection within the
      gastric compartment has been well established, its potential role in the
      maintenance of integrity of the esophageal mucosa in humans has not been explored
      due to the lack of appropriate methodology. METHODS: We have recently developed
      an esophageal perfusion catheter, equipped with two balloons, compartmentalizing
      a 7.5-cm segment of the esophageal lumen. Using this catheter, we studied the
      impact of the luminal perfusion with saline, HCl (0.01 M, pH 2.1), and HCl/pepsin
      solutions (0.5 mg/ml) on esophageal luminal release of PGE2 in 21 asymptomatic,
      presumably healthy volunteers (12 M, 9F; mean age 40 yr). The content of PGE2 in
      its methyl oximated form was measured by RIA (Amersham, IL), using a novel
      iodinated label. Results are expressed as mean +/- SEM. Student's t test was used
      for statistical analysis. RESULTS: Perfusion of the esophageal lumen resulted in
      continuous release of PGE2 into the perfusate at the rate of 1880 +/- 393 pg/min
      during the first 8-min perfusion period. During continuation of perfusion with
      saline, the luminal release of PGE2 was maintained at the rate of 1820 +/- 640
      pg/min during the second 8-min perfusion period. This rate declined (although in
      nonsignificant fashion; p < 0.2) during the third perfusion period, reaching a
      plateau of 1220 +/- 473 pg/min and maintained during the last (period IV)
      perfusion period with saline. Introduction of acid during the perfusion period II
      in the second group of investigated subjects resulted in a rapid and
      statistically significant decline of the luminal release of PGE2 to the value of
      1020 +/- 167 ng/min (p < 0.01). Continuation of esophageal perfusion with acid
      during the next 8-min perfusion period further diminished the luminal release of
      PGE2 to the value of 520 +/- 73; p < 0.001. The significant decline in the rate
      of luminal PGE2 release was still maintained despite the replacement of acid with
      saline during the ending 8-min perfusion (period IV; 560 +/- 80 ng/min; p <
      0.001). Esophageal perfusion with HCl/pepsin solution, in group III subjects,
      potentiated luminal release of PGE2, reaching the value of 1553 +/- 340 pg/min,
      which is 3 times higher than the value of PGE2 observed during corresponding
      perfusion with HCl (period III; p < 0.03). This significant impact of HCl/pepsin
      solution was still maintained despite the substitution of HCl/pepsin with NaCl
      during the last perfusion period, and was still significantly higher (1260 +/-
      220 pg/min; p < 0.02) than the corresponding value during the ending perfusion
      with NaCl after HCl (group II). This study for the first time demonstrates that
      luminal release of PGE2 in humans remains under a significant impact of luminal
      chemical factors such as acid and pepsin. CONCLUSION: The modulatory effect of
      acid and pepsin on esophageal mucosal prostaglandin release may play a role in
      the development of reflux-related mucosal pathology.

PMID- 8147364
TI  - Early stage hepatocellular carcinoma detected during intraoperative
      ultrasonography.
AB  - OBJECTIVES: Recently, it has been recognized that there are increasing incidences
      of hepatocellular carcinoma (HCC) multicentricity. Thus, intraoperatively
      detected hepatic lesions that were once thought to be metastatic lesions now need
      to be carefully reexamined to determine whether they are true metastatic lesions
      or the multicentric development of HCC. METHODS: We investigated the histological
      characteristics of small nodular lesions detected during intraoperative
      ultrasonography in 33 consecutive patients with small HCC who underwent
      laparotomy at our institution. RESULTS: Fourteen nodular lesions were found
      incidentally in 10 of 33 patients (30.3%), and were classified into the following
      three groups: 11 nodules in nine patients (27.3%) were HCC, two nodules in two
      patients (6.1%) were hemangioma, and one nodule in one patient (3.0%) was a large
      regenerative nodule. HCC therefore comprised 78.6% of the intraoperatively
      detected nodular lesions. Of the 11 HCCs, six were hyperechoic, four were
      hypoechoic, and one was isoechoic. Five (83.3%) of six small hyperechoic HCCs and
      two (50.0%) of four hypoechoic HCCs were well differentiated and retained their
      preexisting liver structure. These findings closely coincide with the
      characteristics of early stage HCC. Thus, early stage HCC comprised 63.6% of the
      intraoperatively detected HCC cases. CONCLUSIONS: A certain proportion of small
      satellite HCCs detected during intraoperative ultrasonography in patients with
      small HCC, which were previously thought to be metastatic lesions from the main
      HCC, may instead be early stage HCCs. Such findings would also support the
      concept of the multicentric development of HCC. Approximately 60% of all small
      HCC cases detected intraoperatively may be early stage HCC. As a result, it is
      predicted that the emergence of HCC is either multicentric or unicentric, with
      early intrahepatic spread, although the former seems to be more common.

PMID- 8147365
TI  - Idiopathic anorectal ulceration in patients with human immunodeficiency virus
      infection.
AB  - Opportunistic infections and neoplasms of the anorectum have been reported in
      patients with human immunodeficiency virus (HIV) infection. More recently,
      idiopathic ulcerative lesions of the colon and rectum have been described. At our
      center over a 3-yr period, four patients were identified with ulcerative lesions
      of the rectum and/or anus that remained idiopathic despite an extensive clinical,
      serologic, and histopathologic evaluation. Three patients had the acquired
      immunodeficiency syndrome, and in one anorectal disease was the index
      manifestation of HIV infection. Only one of the patients had recently engaged in
      receptive anal intercourse. The presenting complaints were gastrointestinal
      bleeding in two, which was severe in one, and/or anorectal pain. Multiple
      colonoscopic evaluations with biopsy of the distal colorectum documented a
      solitary ulcer of the rectum in one, solitary ulcer involving the anorectum in
      two, and multiple ulcers of the rectum and anorectum in one. In three patients,
      colonoscopy to the cecum demonstrated no additional lesions. In patients with HIV
      infection, ulcerative lesions of the anorectum may remain unexplained despite an
      exhaustive evaluation. The etiology of these lesions, as well as appropriate
      therapy, remains to be determined.

PMID- 8147366
TI  - Identification of an HNPCC family.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) families are frequently missed
      in the clinical practice setting. The events leading to the diagnosis of a new
      HNPCC family are described, with particular attention to the importance of a
      detailed and extended pedigree, and the delivery of pertinent educational and
      cancer control recommendations to family members. Clinical clues suggestive of
      HNPCC include young age at colon cancer onset (< 45 yr), proximal colon cancers,
      multiple colon cancer, and a family history of colonic cancer or certain
      extracolonic cancers, including endometrium, stomach, small bowel, and urinary
      tract. Once the diagnosis is established, management of high-risk patients must
      be based on an awareness of these cardinal features. The recent identification of
      the cancer susceptibility locus at chromosome 2p15-16 for a subset of HNPCC
      families and its cloning should lead to a blood test for the carrier state. HNPCC
      families must nevertheless be identified before high risk family members can
      enjoy the benefits of progress in molecular biology. This HNPCC family report
      illustrates some of the important clues necessary for recognizing such families,
      and the logistics of detailed evaluation.

PMID- 8147367
TI  - Nonsteroidal anti-inflammatory drug-induced diaphragm disease arising in a
      bypassed ileal segment.
AB  - The formation of mucosal ileal diaphragms has been previously reported in
      patients receiving nonsteroidal anti-inflammatory drugs over extended periods of
      time. Whether this effect is the result of a local or systemic action by the
      medication has remained unknown. We report the first known instance of diaphragm
      disease arising in a segment of ileum that had been bypassed for many years and
      therefore was not exposed normally to luminal contact with the drug. This case
      supports at least a partial systemic mechanism in the production of the lesion.

PMID- 8147368
TI  - Severe upper gastrointestinal bleeding in healthy full-term neonates.
AB  - Severe upper gastrointestinal bleeding is unusual in newborns, and is usually
      seen in sick premature infants. We report on three healthy full-term neonates
      who, after uneventful deliveries, presented with profuse bleeding in the first 48
      h of life. Two infants had duodenal ulcers and one had diffuse hemorrhagic
      gastritis. All three patients responded to conservative medical therapy and have
      shown no recurrence of symptoms during a follow-up period of 1-4 yr.

PMID- 8147369
TI  - Acute suppurative cholangitis associated with choledochal sludge.
AB  - Three patients with acute cholangitis who lacked cholangiographic evidence of
      common bile duct stones are reported. One presented 7 yr after cholecystectomy,
      and the other two had gallbladder sludge but no gallstones. The clinical features
      were mild, consisting of biliary pain, low grade fever without chills, and with
      modest leukocytosis. In each case, free cannulation of the bile duct was not
      possible, necessitating needle-knife papillotomy. After endoscopic
      sphincterotomy, balloon retrieval yielded purulent bile and sludge, but no
      stones. Prompt clinical improvement resulted in all three patients. Cultures of
      bile obtained at endoscopic retrograde cholangiopancreatography grew Escherichia
      coli in two patients and Enterobacter aeruginosa in the other. These observations
      suggest a link between intermittent obstruction due to biliary sludge in the
      common bile duct and bacterial cholangitis. We hypothesize that recurrent passage
      of biliary sludge may precipitate obstructive inflammation and fibrosis of the
      ampulla of Vater. Acute cholangitis should be added to the differential of
      potential complications of biliary sludge.

PMID- 8147371
TI  - Hepatic visceral larva migrans: evolution of the lesion, diagnosis, and role of
      high-dose albendazole therapy.
AB  - An unusual presentation of hepatic involvement of visceral larva migrans is
      described. A 45-yr-old male presented with fever, pain in the right upper
      quadrant, and persistent eosinophilia. Ultrasound initially detected a solitary
      hypoechoic area in the right lobe of the liver which rapidly progressed to
      multiple lesions with peripheral hyperechoic lesions. Aspiration from the lesion
      revealed Charcot-Leyden crystals and sheets of eosinophils. Serology for Toxocara
      canis was strongly positive. Prolonged and high-dose albendazole therapy, in
      combination with antibiotics, was required to treat the patient effectively.

PMID- 8147370
TI  - Dysphagia lusoria in the adult: associated esophageal manometric findings and
      diagnostic use of scanning techniques.

PMID- 8147372
TI  - Xanthogranulomatous cholecystitis masquerading as gallbladder carcinoma.
AB  - We herein present a case of xanthogranulomatous cholecystitis which involved both
      the liver and transverse colon, clinically mimicking gallbladder carcinoma. Such
      cases may sometimes be judged inoperable due to extensive extra-gallbladder
      invasion, and thus it is necessary for physicians to take this lesion into
      consideration when making a diagnosis. An intraoperative biopsy is necessary,
      therefore, even when the features seem to clearly indicate inoperable carcinoma.

PMID- 8147373
TI  - Ketorolac-related giant gastric ulcers.

PMID- 8147374
TI  - Massive hematochezia secondary to graft-versus-host disease and cytomegalovirus.

PMID- 8147375
TI  - Insights into GERD in childhood.

PMID- 8147376
TI  - Microsporidia in HIV diarrhea: present but pathogenic?

PMID- 8147377
TI  - Colonic lavage: flavoring and the importance of patients' compliance.

PMID- 8147378
TI  - Use of GoLYTELY.

PMID- 8147379
TI  - Elevated carbohydrate antigen (Ca19-9) levels in hepatic and renal cystic fluid.

PMID- 8147380
TI  - Re: Endoscopic measurements of colonic polyps.

PMID- 8147381
TI  - Re: Gastrointestinal bleeding from a gastric plasmacytoma.

PMID- 8147382
TI  - Duodenal bacterial overgrowth: which is the best diagnostic tool?

PMID- 8147383
TI  - Massive rectorrhagia and hypovolemic shock in primary amyloidosis.

PMID- 8147384
TI  - Parathyroid hormone-related peptide as a possible cause of hypercalcemia in a
      hepatocellular carcinoma patient.

PMID- 8147385
TI  - Curative endoscopic resection of a carcinoid tumor of the rectum.

PMID- 8147386
TI  - Reversible spastic paraparesis due to cyclosporin toxicity.

PMID- 8147387
TI  - Relationship between H-ras p21 product and p53 protein or high-risk human
      papillomaviruses in esophageal cancer from Kochi, Japan.

PMID- 8147388
TI  - Musculoskeletal symptoms among electricians.
AB  - This study ascertained the presence of musculoskeletal symptoms among
      electricians, in order to evaluate the prevalence of cumulative trauma disorders
      (CTD) in this population. We adapted the CTD surveillance questionnaire used by
      National Institute for Occupational Safety and Health (NIOSH) to assess the
      prevalence of neck, shoulder, elbow, hand/wrist, back, and knee symptoms in the
      year prior to the survey. Questionnaires were completed by 308 apprentices and
      journeymen enrolled in training classes at the local union hall. The participants
      were relatively young individuals, and 86% of the participants were currently
      working as electricians. Participants reported a high prevalence of symptoms
      which occurred more than three times during the past year or which lasted more
      than 1 week. Back symptoms and hand/wrist symptoms were experienced most
      frequently, by about half the population, while elbow symptoms were reported by
      only 15% of participants. Symptom prevalence was lower, but still notable, when
      defined as symptoms which had occurred at least once a month or lasted more than
      a week in the past year. Eighty-two percent of participants reported at least one
      musculoskeletal symptom using the most inclusive definition, while 57% reported
      two or more symptoms. This survey highlights that: 1) low back discomfort is
      common in young construction workers, and resulted in medical care, missed work,
      or light duty for almost 35% of the participants; 2) neck discomfort is also very
      common and required doctor visits or work modification for almost one quarter of
      the participants; 3) these construction workers continued to work with symptoms
      that are classifiable as a CTD; and 4) history of injury is correlated with the
      subsequent prevalence of musculoskeletal symptoms.

PMID- 8147390
TI  - ELF magnetic field exposures in an office environment.
AB  - Potential exposures to extremely low frequency (ELF) magnetic fields were
      investigated in response to worker concerns about an apparent increased
      spontaneous abortion risk in a payroll office environment. Concern in this office
      centered on the use of video display terminals (VDTs), which have been
      investigated as a potential cause of adverse reproductive outcomes among women.
      In this investigation, magnetic field sources were evaluated using a hand-held
      survey meter. Emdex datalogging dosimeters were also used to determine full shift
      personal exposures for 15 women working in the payroll area. On average, the
      exposures of workers to ELF magnetic fields in the payroll office area ranged
      from 1.0 to 6.5 mG with a mean of 3.2 +/- 1.5 mG. The results of this study
      indicate that many sources of ELF magnetic fields, including printers,
      photocopiers, and the electrical distribution system, can contribute to a
      worker's exposure in an office environment.

PMID- 8147389
TI  - Prevalence of depression among electrical workers.
AB  - To address the possible association between electric and magnetic field exposure
      and depression, we analyzed data from the Vietnam Experience Study. In order to
      compare the risk of diagnosed depression, depressive symptoms, and elevations in
      personality scales indicative of depression, we classified employed participants
      as electrical workers (N = 183) and nonelectrical workers (N = 3,861) and
      compared their scores on the Diagnostic Interview Survey (DIS) and the Minnesota
      Multiphasic Personality Inventory (MMPI). Electrical workers in the aggregate
      showed little evidence of increased risk, with the possible exception of an
      increase in elevated MMPI depression scores among short-term workers. Data on
      electricians yielded indications of increased risk for several markers of
      depression. Despite the limited number of electrical workers, uncertainty
      regarding exposure, and our inability to address other workplace exposures, these
      results suggest that electrical workers in general are not at increased risk for
      depression. However, our results encourage further evaluation of depression among
      electricians.

PMID- 8147391
TI  - Assessment of personality traits and psychiatric symptoms in workers in a
      computer manufacturing plant in Japan.
AB  - To investigate personality traits and psychiatric symptoms, we administered the
      Structured Clinical Interview for DSM-III-R Personality Questionnaire (SCID-II
      Screen), the Zung Self-Rating Depression Scale (SDS), and the 30-item version of
      the General Health Questionnaire (GHQ-30) to 781 male computer engineers and 214
      male clerical workers in a computer manufacturing factory. Subjects, aged from 20
      to 49 years, were divided into university and high school graduates. Among the
      university graduates, scores for schizotypal and avoidant personality traits were
      significantly higher in computer engineers than in clerical workers (the effect
      of age was controlled by analysis of covariance). No significant correlation
      between personality traits and years employed was found in the university
      graduate computer engineers. In high school graduates, scores for borderline and
      dependent personality traits were significantly lower in computer engineers than
      in clerical workers (the effect of age was controlled by analysis of covariance).
      Because of the lack of significant association of personality traits and symptoms
      with duration of employment in the university-educated computer engineers, the
      greater prevalence of schizotypal and avoidant personality traits might be
      related to their process of self-selection of job rather than to computer
      manufacturing work. In summary, these data suggest that computer engineering work
      does not cause abnormal personality traits or psychiatric symptoms.

PMID- 8147392
TI  - Comparison of suicide rates among industrial groups.
AB  - Suicide rates among industrial groups were examined systematically using death
      certificate data from 1984 through 1989 in Alabama. Poisson log-linear modelling
      was used to estimate the rate ratios (RR) of industries compared to a referent
      and to adjust for confounding. Marked differences in suicide rates were found
      among industrial groups. The rates ranged from 5.31 to 62.36 per 100,000
      population per year. People employed in public administration had the lowest
      rate. In comparison with public administration, the construction industry had the
      highest risk (adjusted RR = 11.8, 95% confidence interval (CI): 9.6-14.6).
      Employees of the mining industry experienced a similarly high risk (adjusted RR =
      11.5, 95% CI: 8.2-16.3). Persons employed in farming, agriculture services,
      forestry, and fisheries, manufacturing, and transportation, communications, and
      other public utilities industries had intermediate risks. Smaller elevations of
      suicide rates compared to public administration were observed in the wholesale
      trade, retail trade, finance, insurance, and real estate, and services
      industries. The differences of suicide rates may be related to sociodemographic
      differences, self-selection for occupation, ease of access to lethal agents, or
      job stress.

PMID- 8147393
TI  - Retrospective cohort mortality study of workers with potential exposure to
      epichlorohydrin and allyl chloride.
AB  - Previous epidemiologic research has associated potential epichlorohydrin exposure
      with lung cancer and, in conjunction with allyl chloride exposure, to heart
      disease mortality. The study was designed to test both hypotheses by examining
      the mortality experience of 1,064 male employees (12,574 person-years) who had a
      minimum of 1 month work experience between 1957-1986 in the production or use of
      epichlorohydrin and allyl chloride and 1 year total employment duration at Dow
      Chemical's Texas Operations. Vital status follow-up occurred through 1989 of
      which there were 66 total deaths (standardized mortality ratio [SMR] = 80, 95%
      confidence interval [CI] 62-101). There were no significantly elevated SMRs for
      all malignant neoplasms, lung cancer, circulatory system disease, or
      arteriosclerotic heart disease when compared to external (U.S.) or internal
      (Texas Operations) populations. There were no apparent mortality trends with
      cumulative exposure analyses of potential epichlorohydrin exposure with and
      without accompanying allyl chloride exposure. A high prevalence of circulatory
      system death certificates were certified by nonphysicians in the local county and
      more than one third were described in nonspecific terms. The study results are
      not consistent with the prior hypothesized associations. However, the study
      results are limited by the cohort's size, duration of follow-up, relatively few
      number of observed and expected deaths, and the level of potential
      epichlorohydrin exposure experience.

PMID- 8147394
TI  - Mortality and cancer incidence in Stockholm fire fighters.
AB  - Fire fighters are exposed to irritating, asphyxiating, and toxic gases and
      aerosols, to psychological stress, and to physically demanding work. Due to
      differences in fire fighting techniques, exposure conditions for fire fighters
      differ among different countries. The purpose of this investigation was to study
      cancer incidence and mortality in fire fighters who have been working with fire
      fighting methods used in Sweden from the beginning of this century onwards. All
      male fire fighters employed for at least 1 year in the City of Stockholm during
      1931-1983 were traced, and an index of the number of fires fought was calculated
      for each individual. The mortality during 1951-1986 (among 1, 116 fire fighters)
      was lower than expected (SMR = 82; 95% confidence interval 72-91) compared with
      local mortality rates, with a low mortality in circulatory diseases, obstructive
      lung diseases, violent deaths, and suicides. The cancer incidence in 1958-1986
      was equal to the expected (SMR = 100; 95% confidence interval 83-119). However,
      an excess of stomach cancer (18 observed vs. 9.37 expected; SMR = 192, 95% CI 114
      304) was observed. There was also a tendency for higher incidence and mortality
      in stomach and brain cancer with increasing number of fires. There were four
      deaths from brain cancer compared to 0.8 expected (SMR = 496; 95% CI 135-1270) in
      the highest exposure category. Fire fighters are, however, not systematically
      exposed to known stomach or brain carcinogens, and the results need confirmation
      in further studies with extensive exposure evaluations.

PMID- 8147395
TI  - Carpal tunnel syndrome among grocery store workers.
AB  - The California Department of Health Services evaluated carpal tunnel syndrome
      (CTS), a median nerve entrapment condition associated with forceful and
      repetitive wrist motion, among grocery store workers at a large California
      supermarket where a CTS cluster had been reported. Forceful and repetitive wrist
      motion was measured, in three exposure levels, through a job classification
      scheme based upon type of work tasks and average time per week spent performing
      these tasks. A medical questionnaire and measurements of median sensory nerve
      conduction were used to measure CTS. CTS prevalence was 23% based upon a sample
      of 56 participants drawn from a workforce of 69 employees. A relative risk of 8.3
      (95% confidence interval 2.6-26.4) for a history of CTS-like symptoms between the
      high and low exposure level groups held up after adjustment for the potential
      confounders of age, sex, alcohol consumption, and high-risk medical history. It
      was concluded that the basic principles of good ergonomic design should be used
      to prevent or diminish the risk of musculoskeletal injury in the workplace.

PMID- 8147396
TI  - Occupational perilymph fistula.
AB  - A case of occupational perilymph fistula in an ironworker is described. The
      patient was lifting and lowering 200 pounds of steel when he developed sudden
      onset of vertigo. Surgical exploration of the middle ear demonstrated leakage of
      perilymph fluid from the round window. Grafting of the window led to improvement
      of symptoms, but the patient was unable to continue work as an ironworker due to
      difficulty with balance.

PMID- 8147398
TI  - Silicosis surveillance in Ontario: detection rates, modifying factors, and
      screening intervals.
AB  - The Province of Ontario has had a surveillance program for workers in dusty
      industries for almost 70 years. This paper reports the detection rates of
      silicosis among 68,701 silica-exposed individuals who were first exposed to dust
      in 1950 or later, and who were still employed in 1979 or later. The detection
      rate varied strongly with latency, being less than two new cases per 10,000
      examinations during the first two decades from first exposure, reaching two new
      cases per 1,000 examinations at 27 years from first exposure, and averaging
      between two and four new cases per 1,000 examinations thereafter. The silicosis
      incidence rate among miners was only about half that among foundry workers.
      Cigarette smoking was also found to be a risk factor for the diagnosis of
      silicosis. These data were used to model the detection rate of new cases of
      silicosis as a function of the time interval between examinations, and results
      are presented for examination cycles between 2 and 10 years.

PMID- 8147397
TI  - Cohort mortality study of rock salt workers in Italy.
AB  - A cohort mortality study of rock salt workers was carried out in Volterra, Italy.
      The occupational risk factors identified during environmental hygiene surveys
      were high noise levels and exposure to dusts and to chrysotile asbestos. The
      cohort consists of 487 subjects (367 males and 120 females) employed in the mine
      between 1/1/1965 and 12/31/1989. At the end of follow-up, 387 individuals were
      alive (295 males and 92 females), and 100 were decreased (72 males and 28
      females). For two decedents, the cause of death was unknown. Regional rates were
      used for the computation of standardized mortality ratios (SMRs). In the entire
      cohort, observed mortality for all causes was similar to expected (SMR = 98, 100
      obs); SMR for all cancer was 127 (41 obs); for lung cancer, the SMR was 146 (10
      obs). Two cases of pleural mesothelioma, both in males, resulted in a
      statistically significant elevation of this cause (SMR = 741, 90% confidence
      interval (CI) 131-2,332). Two malignant brain tumors were detected (SMR 328, 90%
      CI 58-1,032); one of these was identified as a secondary neoplasm with
      consideration of additional clinical information. Among males, mortality for all
      cancers was significantly increased (SMR = 140, 90% CI 106-192). The observed
      mortality for malignant tumors of the digestive and the respiratory systems was
      higher than expected. In women, two cases of malignant ovarian cancer were
      observed vs. 0.42 expected on the basis of the regional rates. Increased
      mortality from lung and pleural tumors was consistent with the exposure to
      asbestos, which has also been shown to play a role in the development of ovarian
      tumors. The main limitations of this study were the small number of subjects and
      the definition of exposure solely in terms of duration of employment. Further
      studies of rock salt workers are needed to elucidate our findings.

PMID- 8147399
TI  - Estimates of the extent of morbidity and mortality due to occupational diseases
      in Canada.
AB  - OBJECTIVE: To estimate the extent of occupational disease morbidity and mortality
      in Canada by comparing and contrasting four different data sources. DATA SOURCES:
      1) Canadian National Workers' Compensation Boards Statistics, 2) U.S. Bureau of
      Labor Statistics adjusted to Canadian Workforce, 3) California Physician's First
      Reports adjusted to the Canadian Workforce, and 4) proportionate model of overall
      disease incidence obtained through literature review. MAIN FINDINGS: Each data
      source was limited in its ability to provide a true estimate of the extent of
      morbidity and mortality due to occupational disease in Canada. Collectively, an
      estimate of between 77,900 and 112,000 new cases of occupational diseases and
      2,381 to 6,010 occupational disease deaths were obtained. CONCLUSIONS:
      Occupational diseases are a significant and under-estimated cause of morbidity
      and mortality in Canada.

PMID- 8147400
TI  - Toxic health effects including reversible macrothrombocytosis in workers exposed
      to asphalt fumes.
AB  - We investigated an outbreak of irritative and neurotoxic symptoms associated with
      exposure to asphalt fumes in a commercial lighting factory; 27 symptomatic female
      workers were clinically assessed including hematologic testing. When compared
      with a laboratory reference group (n = 107), the workers' mean platelet volume
      (MPV) was significantly higher and mean platelet count was lower (p = 0.013 and p
      = 0.048, respectively). Five months later, the factory's ventilation system was
      substantially modified. Follow-up assessments 6 months postmodification on 15 of
      the original workers documented a significant decline in acute symptoms and a
      lowering of the subjects' mean MPV towards normal (p = 0.0007 by paired t-test).
      The findings suggest that reversible macrothrombocytosis (enlarged platelets) can
      occur among symptomatic workers exposed to asphalt fumes.

PMID- 8147401
TI  - Chewing electric wire coatings: an unusual source of lead poisoning.
AB  - This report describes a case of lead poisoning occurring in an electrician as the
      result of an unusual personal habit, namely, the chewing of lead-containing
      coatings of electric wires. A coating chewing test showed that a few minutes
      after beginning chewing, saliva lead concentration increased from 10 micrograms/l
      to several milligrams per liter. This case is an example of poisoning caused by
      an occupationally related source (coatings containing lead) as a consequence of a
      singular and unconventional worker's habit.

PMID- 8147402
TI  - Muconic acid in urine: a reliable indicator of occupational exposure to benzene.
AB  - In male subjects not occupationally exposed to benzene, the concentration of
      muconic acid (MA) in urine is usually below 0.5 mg/g creatinine. At ambient
      levels of benzene exposure (below 0.01 ppm), the mean MA level was greater in 21
      smokers than in 14 nonsmokers. In 38 male subjects employed in garages and coke
      ovens, a statistically significant correlation was found between the airborne
      concentration of benzene measured with passive monitors and MA in postshift
      urine. The mean postshift MA concentrations corresponding to a benzene 8-hour
      time-weighted average exposure (TWA) of 0.5 and 1 ppm were 0.8 and 1.4 mg/g
      creatinine, respectively.

PMID- 8147403
TI  - Changes in international radiation protection standards.
AB  - The International Commission on Radiological Protection, ICRP, is the only
      organization that has ever effectively set standards at the international level
      for protection from exposure to ionizing radiation. Thus, this paper deals
      primarily with the ICRP, its shortcomings, and changes that should be made in
      ICRP and its operation.

PMID- 8147404
TI  - Clarifying questionable orders.

PMID- 8147405
TI  - Debating NSI.

PMID- 8147406
TI  - Are you losing yourself in codependency?

PMID- 8147407
TI  - Early signs of epidural hematoma.

PMID- 8147408
TI  - Teaching elderly patients about diabetes.

PMID- 8147409
TI  - Using the vacuum dressing alternative for difficult wounds.

PMID- 8147410
TI  - How to manage hip fractures.

PMID- 8147411
TI  - The nursing life. Stolen bases.

PMID- 8147412
TI  - Diarrhea not always linked to tube feedings.

PMID- 8147413
TI  - Iceberging Mr. Washington.

PMID- 8147414
TI  - Beating the unemployment blues.

PMID- 8147415
TI  - Maybe a pot watcher, but never an ostrich.

PMID- 8147416
TI  - Investigating peritoneal irritation.

PMID- 8147417
TI  - Health care consulting boom fuels cutbacks in RN staff.

PMID- 8147418
TI  - Max's homecoming.

PMID- 8147419
TI  - The effects of military-induced separation on family factors and child behavior.
AB  - Data from 61 mothers of school-age children were examined before, during, and
      after military deployment of their husbands. Separations resulted in temporary
      disruptions in families' reported ability to maintain supportive relationships.
      Wives of servicemen sent to the Persian Gulf War reported less nurturance and
      family cohesiveness, and more internalizing and externalizing in children than
      did those whose husbands' deployment was routine.

PMID- 8147420
TI  - Continuity and discontinuity in the affective experiences of parents and
      children: evidence from the New York Longitudinal Study.
AB  - Canonical correlation described continuity and discontinuity in salient
      covariates of emotional and interactional components in parent-child
      relationships among NYLS participants from middle adolescence to young adulthood.
      The results underscore the importance of multiple indicators of parent-child
      relationship quality, and their implications for assessment and intervention
      efforts are discussed.

PMID- 8147421
TI  - Predicting elopement from residential treatment centers.
AB  - To identify predictors of elopement in young patients in residential treatment,
      runaways were compared with a matched sample of nonrunaways. Runaways were more
      likely to have a history of elopement, a suspected history of sexual abuse, an
      affective disorder diagnosis, and parents whose rights had been terminated. The
      results suggested that the likelihood of elopement can be accurately predicted on
      the basis of patient characteristics known at admission.

PMID- 8147422
TI  - Problem-solving appraisal in suicide ideators and attempters.
AB  - The present study expands on previous research proposing a diathesis-stress
      hopelessness model of suicidal behavior. The role of problem-solving appraisal
      within such a conceptual framework and the generalizability of the model across
      both suicide ideators and attempters are explored. Results support the critical
      role played by problem-solving appraisal in predicting both hopelessness and
      suicide ideation.

PMID- 8147423
TI  - Emotional well-being of separated and married women: long-term follow-up study.
AB  - Separated and married women were studied longitudinally. Recently separated women
      reported more growth-oriented coping and positive life changes than did married
      women, but no significant differences were evident six years later. Life strains
      at early time intervals predicted emotional well-being at the last time interval,
      and coping served a stress-buffering function over time.

PMID- 8147424
TI  - Raising grandchildren from crack-cocaine households: effects on family and
      friendship ties of African-American women.
AB  - Changes in family and friendship networks of 71 African-American grandmothers
      raising grandchildren as a consequence of the crack-cocaine epidemic are
      examined. Despite continued strong social ties, many of the women reported
      decreased contact with family and friends other than confidantes and a decline in
      marital satisfaction. Implications of the findings for research, policy, and
      practice are discussed.

PMID- 8147425
TI  - Substance use among the mentally ill: prevalence, reasons for use, and effects on
      illness.
AB  - Substance use among a random sample of mentally ill, community-based patients was
      examined. Current use was found to have declined substantially from a high
      lifetime prevalence, and a family history of substance abuse was associated with
      moderate to heavy use. No association was found between heavy substance use and
      elevated psychopathology, hospitalization, or medication noncompliance. Hospital
      admissions and some symptoms were less prevalent among users preferring
      marijuana.

PMID- 8147426
TI  - The physical restraint of children: is it therapeutic?
AB  - Restraint and seclusion are compared as responses to dangerous aggression, and a
      number of theoretical warrants for the use of physical restraint with children
      are reviewed, with a primary focus on its attachment-promoting possibilities.
      Parallels are drawn between sound physical restraint procedures and the temporal
      phases upon which the holding therapies are based.

PMID- 8147427
TI  - Sex-role socialization: developmental influences on wife abuse.
AB  - Themes central to sex-role socialization are traced, along with the processes by
      which dominance and female deference are developed. Gender differences in parent
      child interactions, peer-group relations, classroom settings, children's
      observations of the marital dyad, and messages from television are examined. The
      link between sex-role socialization and the etiology and maintenance of wife
      abuse is discussed.

PMID- 8147428
TI  - Psychotherapeutic intervention with mothers and children in day care.
AB  - The increasing use of day care permits opportunities for early intervention with
      children whose behavior indicates developing problems. Since these usually
      reflect difficulties in the relationships between children and parents, a
      relatively brief child-led intervention involving the parent, which appears
      helpful and effective, is described and illustrated with case examples.

PMID- 8147429
TI  - Treatment and rehabilitation of the seriously mentally ill in China: impressions
      of a society in transition.
AB  - A visit to a large psychiatric hospital in Beijing revealed determined efforts to
      modernize and improve services for the seriously mentally ill. In sharp contrast
      to current practice in the United States, the mentally ill of China retain strong
      functional and supportive links to their work units and families that offer the
      potential for re-integration into society.

PMID- 8147430
TI  - Maternal sensitivity in the second year: gender-based relations in the dyadic
      balance of control.
AB  - In an investigation of gender-based differences in autonomy and relatedness in
      the mother-toddler dyad, gender-specific stylistic differences were found in
      mothers' sensitivity toward their toddlers. In the context of greater
      sensitivity, boys appeared to control the flow of interactions (initiation and
      maintenance) to a greater extent than did girls.

PMID- 8147432
TI  - 63rd Annual meeting of the American Association of Physical Anthropologists.
      Denver, Colorado, March 29-April 2, 1994. Abstracts.

PMID- 8147431
TI  - Compensation and psychic trauma: a study of Israeli combat veterans.
AB  - The precursors and outcomes of compensation-seeking in Israeli war psychiatric
      casualties were examined. Findings suggest that compensation was sought by
      veterans who had experienced the most severe traumas and had subsequently
      developed the most severe symptoms and functional limitations. Reported range and
      severity of symptoms and functional limitations did not diminish with
      compensation.

PMID- 8147433
TI  - Spinal arthritis and physical stress at Bronze Age Harappa.
AB  - This study examines joint changes in the vertebral skeleton in human remains
      excavated in 1987 and 1988 at Bronze Age Harappa, an urban center of the Indus
      Valley civilization. The sample consists of 23 complete skeletons from primary
      burial context, the partial remains of more than 69 other individuals, and
      hundreds of skeletal elements from secondary context, totalling 3,084 vertebral
      joint margins and articular surfaces. Marginal bone proliferation, pitting of
      articular surfaces, eburnation, and ankylosis were scored macroscopically for
      vertebral body margins and surfaces and posterior apophyseal facet joints.
      Marginal lipping is far more prevalent on the vertebral bodies than on the
      apophyseal facets and surface pitting is also more frequent on vertebral bodies
      although its expression is relatively low overall. Cervical vertebrae in this
      sample exhibit the same amount of marginal new bone and much more surface pitting
      of the vertebral bodies than do either thoracic or lumbar vertebrae; the cervical
      segment also exhibits the most severe expressions of both types of lesions. In
      addition, although the frequencies of cervical and lumbar posterior facet
      involvement are similar, the cervical facets exhibit much more severe lipping as
      well as the only cases of eburnation and ankylosis. Pitting of the posterior
      facets is most common in the lumbar segment, but the cervical examples are the
      only severe cases. It is proposed that the severe joint changes in the cervical
      spine result from trauma, perhaps accumulated microtrauma from activity stresses.
      There are no age or sex associated patterns in the frequency of arthritis
      although this result may be influenced by the small proportions of the total
      sample for which age and sex could be determined.

PMID- 8147434
TI  - Temporal trends in stable isotopes for Nubian mummy tissues.
AB  - From Meroitic to Christian times (350 B.C.-A.D. 1400), Sudanese Nubia experienced
      political, economic, cultural, and environmental upheaval. Change in any one of
      these aspects of ancient lifeways can affect subsistence. Dietary patterns from
      this period are reconstructed by measuring stable carbon and nitrogen isotope
      ratios in tissue samples from 146 mummies excavated from five sites in the Wadi
      Halfa area. On average, delta 13C values of bone collagen, muscle, and skin
      indicate high consumption levels of C3 plants (presumably wheat or barley
      staples, mixed vegetables, and fruits) throughout the sequence. However, during
      the X-Group period (A.D. 350-550), there is a statistically significant increase
      in consumption of C4 plants (millet or sorghum), which are predominant in both
      the archeological record and in modern crop production for most of the Northern
      Sudan. The X-Group period was also associated with a low Nile and political and
      economic restructuring. Increased use of C4 plants on a seasonal basis is also
      indicated by shifting delta 13C values along hair shafts for both X-Group and
      Christian periods. delta 15N values suggest that the major source of protein for
      all time periods came from herbivorous animals. A small, but significant increase
      in 15N over the 1,000-year sequence could be the result of fertilization.

PMID- 8147435
TI  - Mitochondrial DNA analysis in Tibet: implications for the origin of the Tibetan
      population and its adaptation to high altitude.
AB  - Mitochondrial DNAs (mtDNAs) of 54 Tibetans residing at altitudes ranging from
      3,000-4,500 m were amplified by polymerase chain reaction (PCR), examined by high
      resolution restriction endonuclease analysis, and compared with those previously
      described in 10 other Asian and Siberian populations. This comparison revealed
      that more than 50% of Asian mtDNAs belong to a unique mtDNA lineage which is
      found only among Mongoloids, suggesting that this lineage most likely originated
      in Asia at an early stage of the human colonization of that continent. Within the
      Tibetan mtDNAs, sets of additional linked polymorphic sites defined seven minor
      lineages of related mtDNA haplotypes (haplogroups). The frequency and
      distribution of these haplogroups in modern Asian populations are supportive of
      previous genetic evidence that Tibetans, although located in southern Asia, share
      common ancestral origins with northern Mongoloid populations. This analysis of
      Tibetan mtDNAs also suggests that mtDNA mutations are unlikely to play a major
      role in the adaptation of Tibetans to high altitudes.

PMID- 8147436
TI  - Principal component analysis of gene frequencies and the origin of Basques.
AB  - The genetic peculiarity of the Basque population has long been noted. We aim to
      describe Basque distinctiveness in space and assess the internal Basque
      heterogeneity. All these aspects are relevant to the question of the origin of
      Basques. After a thorough literature search, a data base was created containing
      all the available data on gene frequencies in the Iberian Peninsula and France.
      Twenty-nine systems, comprising 71 alleles, were used to carry out a principal
      component (PC) analysis. The results show a sharp peak in the first PC in the
      Basque area, which remains even when the geographic scope is widened to include
      western Europe. As demonstrated by "wombling" analysis, the steeper slope in the
      first PC is found to the east of the Basque area, along the Pyrenees. Measures of
      genetic heterogeneity (such as FST values) within the Basque country, as compared
      to those for non-Basques, do not show a particular internal substructuration in
      the Basque population. The genetic results support a scenario in which the
      Basques are the product of in situ differentiation around the time of the Last
      Glacial Maximum (18,000 B.P.), in agreement with archaeological and linguistic
      data. Isolation from the surrounding populations has allowed the differentiation
      to last for millennia, but has erased the differences existing among Basques.

PMID- 8147437
TI  - Growth status of school-age Mayan children in Belize, Central America.
AB  - This paper reports the growth status of a sample of Mopan Maya school children
      living in a rural village in Belize. These children exhibit a growth pattern
      typical of chronic undernutrition, in that a high percentage are stunted (66%),
      but virtually none are wasted by WHO criteria. The Belize Maya children are
      compared to four other Amerindian groups and found to be shorter and lighter than
      a semi-urban group from Guatemala, but taller and heavier than three rural groups
      from Guatemala and Mexico. The Belize children exhibit the largest arm
      circumferences among all five groups. This pattern of growth is discussed in
      light of current ideas concerning the contribution of genetics vs. environment to
      childhood growth and population well-being.

PMID- 8147438
TI  - Variability at the carpometacarpal and midcarpal joints involving the fourth
      metacarpal, hamate, and lunate in catarrhini.
AB  - Intraspecies variability is investigated in two regions of the wrist, for the
      purpose of determining whether patterns may be discerned in the variability that
      may be compared in the functional and phylogenetic analysis of living and fossil
      catarrhines. In the midcarpal joint region, two lunatohamate configuration
      patterns are found, and at the fourth carpometacarpal joint four types of
      configuration are identified. These two sites previously were reported to show
      almost continuous variability in humans, thus precluding comparison with other
      species. The different types of configuration in our study are delineated on the
      basis of their relation to differences in joint function. At the lunatohamate
      site there is a strong tendency in each species examined for one type to dominate
      in frequency. At the fourth carpometacarpal joint there is a tendency for one
      type or for two related types to predominate in each species. The chimpanzee
      sample exhibits the least variability of all species studied in joint
      configuration at the two sites. Australopithecus afarensis has a combination of
      joint types in these regions likely to be found today in only a small percentage
      of living Hominoidea. We conclude that patterns may be discerned at some joints
      in what was formerly considered to be a continuum of variation. Since these
      patterns (joint types) differ in their relative frequencies among living species,
      the frequency differences may be useful as a guide to the reconstruction of
      phylogenetic relationships and of potential wrist functions in fossil species.

PMID- 8147439
TI  - Multivariate analysis of the sexual dimorphism of the hip bone in a modern human
      population and in early hominids.
AB  - A large sample of hip bones of known sex coming from one modern population is
      studied morphologically and by multivariate analysis to investigate sexual
      dimorphism patterns. A principal component analysis of raw data shows that a
      large amount of the hip bone sexual dimorphism is accounted for by size
      differences, but that sex-linked shape variation is also very conspicuous and
      cannot be considered an allometric consequence of differences in body size
      between the sexes. The PCA of transformed ("shape") variables indicates that the
      female hip bones are different in those traits associated with a relatively
      larger pelvic inlet (longer pubic bones, a greater degree of curvature of the
      iliopectineal line, and more posterior position of the auricular surface), as
      well as a broader sciatic notch. The analysis of nonmetric traits also shows
      marked sexual dimorphism in the position of the sacroiliac joint in the iliac
      bone, in the shape of the sciatic notch, in pubic morphology, and in the presence
      of the pre-auricular sulcus in females. When the australopithecine AL 288-1 and
      Sts 14 hip bones are included in the multivariate analysis, they appear as "ultra
      females." In particular these early hominids exhibit extraordinarily long pubic
      bones and iliopectineal lines, which cannot be explained by allometry.

PMID- 8147440
TI  - Mechanical and spatial determinants of Paranthropus facial form.
AB  - It is well documented in the anthropological literature that the distinctive
      morphology of the "robust" hominid facial skeleton reflects its dietary
      specialization. Rak (1983) has provided the most comprehensive evaluation of
      Paranthropus facial morphology and this important study concluded that bone
      strain generated during mastication was responsible for the scaling of measures
      of facial height and breadth. The present study evaluated Rak's analysis by
      examining the relationship between bizygomatic breadth and facial height in an
      ontogenetic series of Pan and Gorilla crania. Results of this analysis indicate
      that facial height and breadth dimensions were not mechanically scaled in the
      "robust" australopithecines. Structural analysis of African ape facial maturation
      was also used to examine alternative spatial methods of malar elongation in
      Paranthropus. It is concluded that the increased height of the malar region in
      these specimens is not related to either vertical expansion of the posterior
      facial skeleton or to expansion of the temporal fossa. Malar elongation is,
      however, consistent with a derived pattern of facial growth in crania possessing
      a thickened hard palate.

PMID- 8147441
TI  - Brief communication: additional cranial remains from Vindija cave, Croatia.
AB  - Two additional cranial specimens from Vindija cave, Croatia, are described. One
      specimen is a zygomatic, providing the first information about the midfacial
      anatomy of the Vindija hominids. The other specimen is a frontal/supraorbital
      torus fragment. Both specimens exhibit morphology typically associated with
      Neandertals. They derive from level G1 and provide further indication that both
      the level G3 and G1 hominids at Vindija represent Neandertals.

PMID- 8147442
TI  - Of the muse and moods mundane.

PMID- 8147443
TI  - George Gordon, Lord Byron 1788-1824.

PMID- 8147444
TI  - Mind and mood in modern art, II: Depressive disorders, spirituality, and early
      deaths in the abstract expressionist artists of the New York School.
AB  - This article documents the high prevalence of mood disorders in a group of 15 of
      the mid-twentieth-century Abstract Expressionist artists of the New York School.
      These artists, using the technique of psychic automatism (based on free
      association) in order to reveal unconscious material, created a psychologically
      and spiritually significant art that addressed the mythic themes of creation,
      birth, life, and death. Over 50% of the 15 artists in this group had some form of
      psychopathology, predominantly mood disorders and preoccupation with death, often
      compounded by alcohol abuse. At least 40% sought treatment and 20% were
      hospitalized for psychiatric problems. Two committed suicide; two died in single
      vehicle accidents while driving; and two others had fathers who killed
      themselves. Many of these artists died early deaths, and close to 50% of the
      group (seven of 15) were dead before the age of 60. The material presented in
      this article suggests the following formulation and hypothesis. Depression
      inevitably leads to a turning inward and to the painful reexamination of the
      purpose of living and the possibility of dying. Thus, by bringing the artist into
      direct and lonely confrontation with the ultimate existential question, whether
      to live or to die, depression may have put these artists in touch with the
      inexplicable mystery that lies at the heart of the "tragic and timeless" art that
      the Abstract Expressionists aspired to produce.

PMID- 8147445
TI  - Melancholic symptom features and DSM-IV.
AB  - OBJECTIVE: The purpose of this article is to provide an overview of existing
      systems for the diagnosis of the endogenous (melancholic) subtype of major
      depression. METHOD: The authors review the critical empirical research examining
      this subtype and discuss its implications for DSM-IV. They examine the
      relationship of endogenous/melancholic symptoms to other clinical features,
      treatment response, selected laboratory tests, consistency across episodes,
      family history, and particular courses of illness. RESULTS: Melancholic symptom
      features are predictive of a positive response to ECT and to tricyclic
      antidepressants in the severely ill. Key features include psychomotor
      retardation, unreactive mood, pervasive anhedonia, and distinct quality of mood.
      Melancholic features are associated with shorter REM latency and/or
      nonsuppression of cortisol during the dexamethasone suppression test. Depressive
      episodes that are not melancholic may take on melancholic features with
      repetition and passage of time in some individuals. Once melancholic features are
      present, it is unclear whether they repeat across subsequent episodes.
      Melancholic features are not uniquely associated with a positive family history
      of depression per se, but they may be especially associated with a family history
      of severe depression. CONCLUSIONS: The available evidence suggests some clinical
      utility and some (albeit not entirely consistent) validity for the concept of
      melancholic features. Consequently, DSM-IV will retain the designation "with
      melancholic features," return to the shorter DSM-III feature listing, and broaden
      the designation by requiring either unreactive mood or pervasive anhedonia but
      not both. Further research on this subgroup is indicated.

PMID- 8147446
TI  - Human brain receptors, III. Molecular Model: G protein-coupled receptor.

PMID- 8147447
TI  - Do depressed men and women respond similarly to cognitive behavior therapy?
AB  - OBJECTIVE: A great majority of the evidence pertaining to the effectiveness of
      the time-limited psychotherapies as treatments of major depression are derived
      from studies of either predominantly or entirely female subject groups. Depressed
      men and women differ in a number of important respects that may alter the course
      of affective disorder, and as a result, they may also differ in their responses
      to psychotherapy. In this study the outcomes of 40 men and 44 women treated with
      cognitive behavior therapy were compared. METHOD: The patients were interviewed
      with the Schedule for Affective Disorders and Schizophrenia and diagnosed
      according to the Research Diagnostic Criteria and DSM-III-R criteria.
      Subsequently, they were assessed every other week (with the Hamilton Depression
      Rating Scale, Beck Depression Inventory, and Global Assessment Scale) during a
      standardized, time-limited cognitive behavior therapy protocol. The outcomes of
      the men and women were compared by means of a series of analyses of variance and
      covariance and survival analyses. RESULTS: There were several significant
      pretreatment differences, and the men attended significantly fewer therapy
      sessions than the women. Although the men and women generally had comparable
      responses, patients with higher pretreatment levels of depressive symptoms,
      particularly women, had poorer outcomes. CONCLUSIONS: This study provides further
      evidence of gender-specific differences in depressed patients' symptoms and
      treatment utilization. Cognitive behavior therapy appears to be a comparably
      useful outpatient treatment for men and women. However, either more intensive
      cognitive behavior therapy or alternative methods of treatment may be warranted
      for patients with more severe syndromes.

PMID- 8147448
TI  - Multisite data reanalysis of the validity of rapid cycling as a course modifier
      for bipolar disorder in DSM-IV.
AB  - OBJECTIVE: The validity of rapid cycling as a distinct course modifier for
      bipolar disorder was assessed by comparing patients with and without a history of
      rapid cycling (4 or more affective episodes in 12 months) on demographic,
      clinical, family history, and outcome variables. These data were also used to
      formulate operational criteria for the modifier. METHOD: Data on subjects with
      rapid-cycling (N = 120) and nonrapid-cycling (N = 119) bipolar disorder from four
      sites were pooled and analyzed by using case-control and historical cohort
      methods. RESULTS: The rapid-cycling group contained more women and more subjects
      from higher social classes than the nonrapid-cycling group. Family history did
      not differ between the groups. The diagnosis had predictive validity in that the
      rapid-cycling patients had more episodes than the nonrapid-cycling patients
      during prospective follow-up. The relationship between gender and episode
      frequency supported the validity of the cutoff point of 4-8 episodes per year.
      The data regarding whether patients with rapid cycling based on truncated
      episodes more closely resembled rapid-cycling or nonrapid-cycling patients were
      equivocal. Patients whose only rapid cycling was associated with antidepressants
      resembled spontaneously rapid-cycling patients, while the majority of
      spontaneously rapid-cycling patients also had periods of antidepressant
      associated rapid cycling. CONCLUSIONS: The validity of rapid cycling as a
      distinct course modifier for bipolar disorder is supported by differences in
      gender, prospectively assessed outcome, and perhaps social class between rapid
      cycling and nonrapid-cycling patients. The relationship of gender to episode
      frequency supports the cutoff of 4 or more episodes per year.

PMID- 8147449
TI  - Depressive distress among homosexually active African American men and women.
AB  - OBJECTIVE: Although early surveys of psychological adjustment among gay men and
      lesbians suggest only minor and not clinically relevant differences from
      heterosexual populations, concerns about psychiatric morbidity associated with
      HIV infection have renewed interest in the prevalence of psychological distress
      in this population, particularly among gay men. These later studies have focused
      primarily on white men. However, research indicates higher crude prevalence rates
      of psychological distress in community-drawn samples of African American subjects
      than in white subjects and also higher rates in women than in men. The authors
      examined rates of depressive distress and suicidal thoughts among homosexually
      active African American men and women who might be especially at risk for
      psychiatric morbidity due to multiple stigmatized social statuses. METHOD: Two
      nationally recruited groups of homosexually active African Americans (829 men and
      603 women) completed self-administered questionnaires, including the Center for
      Epidemiologic Studies Depression Scale. RESULTS: Homosexually active black women
      were as distressed as HIV-infected gay black men. Men with symptomatic HIV
      disease were significantly more distressed than men who were HIV infected but
      asymptomatic, HIV-antibody negative, or whose HIV status was unknown. Both men
      and women reported distress levels in excess of those previously reported in
      studies of blacks or primarily white gay men. CONCLUSIONS: Further research is
      needed to identify specific predictors of life stressors and lack of social
      support among homosexually active African Americans who appear to be at higher
      risk for depressive distress.

PMID- 8147450
TI  - Suicide in major depression.
AB  - OBJECTIVE: The purpose of this study was to examine a sample representing all
      suicide victims with current DSM-III-R major depression in Finland within 1 year
      in aspects relevant to suicide prevention, including comorbidity, clinical
      history, current treatment, suicide methods, and communication of suicide intent.
      METHOD: Using the psychological autopsy method, the authors examined all 71
      suicide victims with current unipolar DSM-III-R major depression, taken from a
      random sample of 229 subjects representing 16.4% of all suicide victims in
      Finland in 1 year. RESULTS: The majority (85%) were complicated cases with
      comorbid diagnoses, and comorbidity varied according to the subjects' sex and
      age. Three-quarters had a history of psychiatric treatment, but only 45% were
      receiving psychiatric treatment at the time of death. Most suicide victims had
      received no treatment for depression. Only 3% had received antidepressants in
      adequate doses, 7% weekly psychotherapy, and 3% ECT. None of the 24 psychotic
      subjects had received adequate psychopharmacological treatment. Few (8%) had used
      an antidepressant overdose as a suicide method. Men had received less treatment
      for depression and had more commonly used violent suicide methods. CONCLUSIONS:
      Although about half of the suicide victims with major depression were receiving
      psychiatric care at the time of death, few were receiving adequate treatment for
      depression. There were significant sex differences in current and previous
      treatment and suicide methods. For suicide prevention in major depression, it
      would seem crucial to improve treatment and follow-up, for males with major
      depression, in particular.

PMID- 8147451
TI  - Clinical characteristics of patients with concurrent major depressive disorder
      and panic disorder.
AB  - OBJECTIVE: This study was designed to test the hypothesis that patients with both
      major depressive disorder and panic disorder exhibit more clinical symptoms and
      have a more protracted course of illness than patients with major depressive
      disorder only. METHOD: The authors compared standardized clinical evaluations
      (from Schedule for Affective Disorders and Schizophrenia interviews) of 119
      patients with major depressive disorder only and 57 patients with major
      depressive disorder and concurrent panic disorder. Clinical and demographic
      variables were included. RESULTS: The patients with both disorders reported
      symptoms of major depressive disorder earlier in life and also required treatment
      and hospital admission earlier in life. Many clinical features during the index
      episode were significantly more severe in the patients with both disorders. A
      logistic regression identified a "panic index" consisting of the symptoms of
      somatic anxiety, phobia, indecisiveness, and feelings of inadequacy. Scores on
      this index allowed proper classification of patients to either of the two
      diagnostic groups with high reliability. CONCLUSIONS: In major depressive
      disorder, the presence of panic disorder is suggestive of a more severe and
      precocious form of illness.

PMID- 8147452
TI  - Anxiogenic effects of CO2 and hyperventilation in patients with panic disorder.
AB  - OBJECTIVE: Previous studies have indicated that patients with panic disorder are
      more likely than normal subjects to have acute panic attacks during inhalation of
      CO2, but methodological objections have been raised. In this study the authors
      attempted to address three of these methodological problems by ensuring that
      raters who assessed whether panic attacks occurred were blind to subjects'
      diagnoses, by randomizing the order of administration of 5% CO2 and
      hyperventilation, and by challenging a greater number of subjects with 7% CO2.
      METHOD: Patients with panic disorder and normal subjects underwent 20-minute
      inhalations of 5% CO2 and 7% CO2 and 15 minutes of room-air hyperventilation.
      Ratings of panic/no panic during each condition were made separately by an
      assessor blind to diagnosis and by the subject. Scores on four panic rating
      scales were also recorded before and after each intervention. RESULTS: Room-air
      hyperventilation caused panic attacks in a small number of patients; the
      difference in panic rate between patients and comparison subjects was
      statistically significant by the subjects' but not by the raters' assessment.
      Panic rates during 5% CO2 and 7% CO2 were significantly greater among the
      patients by both assessments; the panic rate was greatest during 7% CO2. Order of
      administration did not significantly affect panic rates for hyperventilation and
      5% CO2. CONCLUSIONS: Panic patients were clearly more sensitive to the anxiogenic
      effects of CO2 than comparison subjects, and CO2 was a more potent anxiogenic
      stimulus than room-air hyperventilation. Seven percent CO2 discriminated best
      between patients and comparison subjects and should be the focus of further
      research.

PMID- 8147453
TI  - PTSD among Israeli former prisoners of war and soldiers with combat stress
      reaction: a longitudinal study.
AB  - OBJECTIVE: The aim of this study was to assess the long-term impact of war
      captivity and combat stress reaction on rates of posttraumatic stress disorder
      (PTSD) in Israeli veterans of the 1973 Yom Kippur war. METHOD: One hundred sixty
      four former prisoners of war (POWs), 112 veterans who had had combat stress
      reaction, and 184 combat veteran comparison subjects filled out the PTSD
      Inventory, a self-report scale based on the DSM-III-R criteria for PTSD. The
      inventory diagnoses past and present PTSD, assesses its intensity, and provides a
      symptom profile. RESULTS: Thirty-seven percent of the veterans who had had combat
      stress reaction, 23% of the former POWs, and 14% of the comparison subjects had
      had diagnosable PTSD at some time in the past. The current rates were 13%, 13%,
      and 3%, respectively. The results showed different recovery rates over time:
      almost two-thirds of the veterans with combat stress reaction who had had PTSD in
      the past recovered, while less than one-half of the POW group showed this
      improvement. CONCLUSIONS: These findings indicate that small but significant
      proportions of the POWs and veterans with combat stress reaction were still
      suffering from PTSD almost two decades after the war. The different recovery
      rates in the two groups may reflect the differences in duration and severity of
      stressors, the impact of immediate intervention on long-term adjustment, or both.

PMID- 8147454
TI  - Validity of self-defeating personality disorder.
AB  - OBJECTIVE: The purpose of this study was to assess the validity of DSM-III-R self
      defeating personality disorder. METHOD: Applicants for inpatient treatment of
      personality disorders (N = 100) or psychoanalysis (N = 100) were independently
      evaluated face to face by experienced clinicians using the Structured Clinical
      Interview for DSM-III-R and the Personality Disorder Examination. Internal
      consistency; agreement between assessments; diagnostic efficiency of criteria;
      prevalence; sex ratio; comorbidity with axis I and II disorders; and relationship
      to education, current employment, and selection for psychoanalytically oriented
      treatment were examined. RESULTS: The internal consistency of the criteria set
      and the agreement between psychiatric assessments of self-defeating personality
      disorder were fair. The most discriminating criteria were those referring to a)
      choices leading to disappointment, failure, or mistreatment and b) rejection of
      opportunities for pleasure. A consensus diagnosis of self-defeating personality
      disorder was more common than all but three other axis II disorders. The sex
      ratio of the subjects with this diagnosis was not significantly different from
      the sex ratio of the entire subject group or of patients with other personality
      disorders. Significant comorbidity with borderline and dependent personality
      disorders and with current mood disorders was found. Patients with self-defeating
      personality disorder resembled patients with other personality disorders in
      educational attainment and treatment assignment. They were more likely to be
      employed. CONCLUSIONS: These data lend little support to the validity of self
      defeating personality disorder as a separate personality disorder category.

PMID- 8147455
TI  - Concordance between patients and informants on the personality disorder
      examination.
AB  - OBJECTIVE: Difficulties in the assessment of personality disorders and the
      burgeoning interest in axis II have led to increased use of informants when
      studying these conditions. The present study sought to evaluate the
      correspondence between patients and their informants on symptoms of personality
      disorders. METHOD: A total of 105 outpatients and knowledgeable informants were
      independently interviewed by using the Personality Disorder Examination, a widely
      used instrument for the full range of personality disorders. RESULTS: Diagnostic
      concordance between interviews was low (median kappa = -0.01), while correlations
      between dimensional scores were somewhat higher (median kappa = 0.36). Overall,
      patient interviews showed more pathology than interviews with informants.
      However, many of the symptoms obtained from informants were not reported by
      patients. CONCLUSIONS: These data suggest that patient-informant concordance for
      axis II disorders is poor for diagnoses but somewhat better for dimensional
      scores. There was no evidence that low agreement can be explained by patients
      attempting to present themselves in a favorable light. Further work is necessary
      to elucidate the reasons for discordance and determine which data source provides
      the most valid information.

PMID- 8147456
TI  - Effects of informant mental disorder on psychiatric family history data.
AB  - OBJECTIVE: In family history interviews, mentally ill individuals ascribe their
      own disorders to relatives more frequently than informants who are not ill.
      Whether this reflects increased or decreased reporting accuracy remains unknown.
      This study addressed this issue by examining the sensitivity and specificity of
      diagnoses based on information from different types of informants classified by
      their own illness status. METHOD: Both members of 2,193 pairs of individuals
      participating in a psychiatric family study were directly interviewed. One
      individual in each pair (the informant) also provided family history data about
      the other (the subject). Informant-subject pairs were grouped according to the
      illness status of the informant based on the direct interview. Patterns of
      ascription of mental illness to subjects by groups of ill and not-ill informants
      were then compared with the subjects' psychiatric status based on direct
      interview. RESULTS: For depression, alcoholism, panic disorder, and "any
      diagnosis," ill informants demonstrated significantly increased sensitivity in
      family history reports when compared to never-mentally-ill informants;
      specificity, by contrast, was always significantly reduced. For each disorder,
      the aggregate disorder rate derived from family history reports was closer to the
      rate derived from direct interviews if information from ill informants as a group
      was used. CONCLUSIONS: The sensitivity and specificity of family history
      information appears to vary systematically with informant mental illness status.
      This may introduce a serious bias into psychiatric family study data, leading to
      overestimation of the strength of the tendency for mental disorders to "run in
      families." Family studies that rely on the informant method in their diagnostic
      evaluations should be aware of this problem.

PMID- 8147457
TI  - Pharmacotherapy in outpatient psychiatric practice.
AB  - OBJECTIVE: This article examines some of the factors that influence the extent to
      which psychiatrists provide pharmacotherapy to their outpatients. METHOD: Data
      from the 1988-1989 APA Professional Activities Survey are used to define the
      characteristics of psychiatrists who prescribe medications to a high, medium, and
      low proportion of their outpatients in treatment. Outpatient assessments,
      evaluations, or consultations were excluded from this analysis. Correlations
      between psychiatric practice characteristics and rates of pharmacotherapy are
      examined. RESULTS: One-third of psychiatrists prescribed medications to less than
      46.7% of their outpatients, one-third prescribed medications to between 46.7% and
      84.6%, and one-third prescribed medications to over 84.6% of their outpatients.
      The psychiatrists in the last group included a proportionately higher number of
      young psychiatrists, men, nonwhites, those without psychoanalytic or child
      psychiatry training, those with larger caseloads, and those who worked in the
      public sector. These psychiatrists also treated a disproportionately large number
      of patients with schizophrenia and related psychotic disorders. In a multivariate
      model, clinical, practice, and educational variables, but not demographic
      variables, were found to correlate with the extent of pharmacotherapy provided.
      CONCLUSIONS: Psychiatrists vary widely in the extent to which they are involved
      in prescribing psychotropic medications. The diagnostic composition of their
      caseload, their work setting, and their educational background, but not their
      demographic characteristics, appear to influence the extent of their involvement.

PMID- 8147459
TI  - Exposure to ambient light in patients with winter seasonal affective disorder.
AB  - In a study of the quantitative relationship between ambient light and depression
      in winter seasonal affective disorder, 13 outpatients and 13 normal comparison
      subjects each wore a light monitor for 1 week. The patients and normal subjects
      showed similar light exposure profiles; among the patients, severity of
      depression was inversely related to photoperiod, and there was a trend toward a
      correlation between greater severity of depression and later time of onset of
      morning light exposure. These findings suggest that vulnerability to short
      photoperiods may be related to depression in winter seasonal affective disorder.

PMID- 8147458
TI  - Characteristics of psychoanalytic patients under a nationalized health plan: DSM
      III-R diagnoses, previous treatment, and childhood trauma.
AB  - OBJECTIVE: This article reports the results of a survey to collect data on the
      characteristics of patients in psychoanalysis under a nationalized health
      insurance scheme. METHOD: A questionnaire, to be answered anonymously, was sent
      to all 174 accredited psychoanalysts in Ontario, Canada. Part 1 of the
      questionnaire consisted of 38 questions on the analyst's pattern of practice.
      Part 2, also to be filled out by the analyst, consisted of 452 questions on the
      demographic characteristics, childhood traumas, DSM-III-R diagnoses, and
      indications for psychoanalysis of each of the analyst's patients. RESULTS: One
      hundred seventeen analysts responded--a survey response rate of 67%--with data on
      580 patients. Fifty-nine percent (N = 344) of patients were women, and 41% (N =
      236) were men. Eighty-two percent had attempted other forms of treatment,
      including briefer forms of psychotherapy and medication, prior to psychoanalysis.
      During childhood, 23% had had traumatic separations, 23% had been sexually
      abused, 22% had been physically abused, and 21% had had a parent or sibling die.
      The mean number of adult psychiatric disorders at the beginning of analysis was
      four, and the mode was two. CONCLUSIONS: In a nationalized health insurance
      scheme, the psychoanalytic patients were mostly women, they had high rates of
      trauma and psychopathology, and they had attempted other forms of briefer
      treatment before resorting to psychoanalysis.

PMID- 8147460
TI  - Mononuclear leukocyte levels of G proteins in depressed patients with bipolar
      disorder or major depressive disorder.
AB  - Stimulatory (Gs) and inhibitory (G(i)) guanine nucleotide binding protein alpha
      subunit levels were measured in mononuclear leukocytes from 22 drug-free
      depressed patients (eight with bipolar disorder, 14 with major depressive
      disorder) and a comparison group of 17 age- and sex-matched healthy subjects. The
      levels of Gs alpha and G(i) alpha were significantly higher (160% and 114%,
      respectively) in the bipolar patients, but not the patients with major depressive
      disorder, than in the healthy subjects. These data add to the evidence for
      abnormalities in G protein levels and function in the pathophysiology of bipolar
      disorder.

PMID- 8147461
TI  - Major depression and the self-criticism and dependency personality dimensions.
AB  - The Depressive Experiences Questionnaire was used to assess the personality
      dimensions of dependency and self-criticism in 52 depressed patients before and
      after treatment and in 22 healthy family practice patients. Neither personality
      dimension was significantly influenced by change in depressed mood, and the
      recovered depressed patients had higher levels of dependency and self-criticism
      than the comparison subjects.

PMID- 8147462
TI  - Diagnostic rate of comorbid personality disorder in elderly psychiatric
      inpatients.
AB  - Among 547 elderly inpatients grouped by DSM-III-R axis I diagnoses, the
      diagnostic rate of comorbid personality disorder varied four-fold, from 6% in
      patients with an organic mental disorder to 24% in those with major depression.
      The previously reported low prevalence of comorbid personality disorder in
      geriatric patients may be due to its lower rate of diagnosis among patients with
      organic mental disorders.

PMID- 8147463
TI  - Gun control and suicide in Ontario.
AB  - To assess the impact of the 1978 Canadian gun control law on suicide rates in
      Ontario, the authors compared firearm and nonfirearm suicide rates for 1965-1977
      with those for 1979-1989. There was a decrease in level and trend over time of
      firearm and total suicide rates and no indication of substitution of other
      methods. These decreases may be only partly due to the legislation.

PMID- 8147464
TI  - Decreased anxiety in lung transplant recipients.

PMID- 8147465
TI  - Life-threatening hypokalemia associated with excessive licorice ingestion.

PMID- 8147466
TI  - Compulsive symptoms associated with frontal lobe injury.

PMID- 8147467
TI  - Excessive lithium reabsorption by the proximal tubules.

PMID- 8147468
TI  - Neutropenia in a patient receiving clozapine.

PMID- 8147469
TI  - Development of urinary retention during treatment with clozapine and meclizine.

PMID- 8147470
TI  - Fluoxetine-initiated ovulatory cycles in two clomiphene-resistant women.

PMID- 8147471
TI  - Sertraline and akathisia.

PMID- 8147472
TI  - Sertraline efficacy in depressed combat veterans with posttraumatic stress
      disorder.

PMID- 8147473
TI  - Controlling panic attacks with fenfluramine.

PMID- 8147474
TI  - Benjamin Franklin: founder of cognitive therapy?

PMID- 8147475
TI  - S. Weir Mitchell (1829-1914): physician and poet.

PMID- 8147476
TI  - Transdermal nicotine after smoking cessation.

PMID- 8147477
TI  - Practice guideline for adult mayor depressive disorder.

PMID- 8147478
TI  - Psychotherapist-patient privilege.

PMID- 8147479
TI  - Schizophrenia and choline acetyltransferase.

PMID- 8147480
TI  - Alexithymia and panic disorder.

PMID- 8147481
TI  - Alexithymia and panic disorder.

PMID- 8147482
TI  - Multiple personality disorder diagnosis: a house of cards?

PMID- 8147484
TI  - Position statement on HIV infection and psychiatric hospitalization of children
      and adolescents.

PMID- 8147483
TI  - Policy guideline on clean needle and syringe exchange.

PMID- 8147485
TI  - Pathology of patients with Chagas' disease and acquired immunodeficiency
      syndrome.
AB  - The main pathologic findings in 23 patients with acquired immunodeficiency
      syndrome (AIDS) and Chagas' disease are reviewed; five are from our own
      experience and 18 from the literature. The presence of Trypanosoma cruzi
      parasites and/or T. cruzi antibodies in blood and cerebrospinal fluid was
      recorded and computerized tomograms of the brain were evaluated. Twenty (87%) of
      the 23 subjects developed severe, multifocal or diffuse meningoencephalitis with
      necrosis and hemorrhage associated with numerous tissue parasites. The second
      most severely affected site was the heart. Seven (30.4%) of the 23 cases had
      myocarditis on pathologic examination. It was acute in four patients, chronic in
      two, and simultaneously acute and chronic in one. Acute myocarditis and
      meningoencephalitis are interpreted as being caused by relapses of chronic T.
      cruzi infections. An AIDS permissive role is suggested for these conditions since
      immunologic defense against T. cruzi is mediated mainly by T lymphocytes, whose
      CD4 subpopulation is depleted in patients with this disease. Consequently, AIDS
      is a factor that may favor the reactivation of T. cruzi infections. The lesions
      reported in the association of Chagas' disease with AIDS were compared with those
      reported from patients without AIDS having fatal, acute, vector-transmitted
      infections, contaminated blood transfusions, or accidental exposures in the
      laboratory. For the latter three, meningoencephalitis is uncommon. Only
      immunosuppressed cases of Chagas' disease have been described as having a
      pseudotumoral presentation that shows expanding lesions with a mass effect in the
      cranial cavity that causes intracranial hypertension and simulates neoplasms
      (tumors such as gliomas, lymphomas, metastases, etc.).

PMID- 8147486
TI  - Natural history of Schistosoma mansoni infection in mice: egg production, egg
      passage in the feces, and contribution of host and parasite death to changes in
      worm numbers.
AB  - Mice, C57Bl/6N (B6) and BALB/cAnN (BALB), infected with Schistosoma mansoni were
      examined 8-26 weeks postinfection (PI) to estimate the fecundity of the worms and
      the contribution of death of worms and the death of heavily infected mice to the
      decrease in worm numbers in chronic infections. Portal worms were recovered by
      perfusion and the lungs were examined for parasites shunted from the portal
      circulation. Animals that died were more heavily infected than those that
      survived. Between eight and 12 weeks PI, this loss of worms resulted in a net
      decrease of approximately 19% of worm pairs in surviving BALB mice, but of only
      4% in B6 mice. Loss of portal worms to the lungs after the eighth week of
      infection was 9-13% of portal worms in BALB mice and 3-4% in B6 mice. The
      estimated rates of egg production by S. mansoni decreased slightly with time in
      both strains of mice. At 12 and 20 weeks PI, tissue eggs per worm pair and eggs
      passed in the feces per worm pair often decreased as the intensity of infection
      increased. We do not consider the loss of worms in the murine host relevant to
      most infections in humans because of the high intensity of infection relative to
      body size in mice and the high frequency of severe portal obstruction in murine
      infections.

PMID- 8147487
TI  - Kinetics of egg production and egg excretion by Schistosoma mansoni and S.
      japonicum in mice infected with a single pair of worms.
AB  - Individual male and female schistosomes approximately three weeks of age were
      implanted into the portal venous system of C57Bl/6 mice to produce infections
      with a single pair of Schistosoma mansoni or S. japonicum. Mice were killed
      between seven and 54 weeks after infection. Worm fecundity was measured by
      counting eggs accumulating in the tissues and eggs passed in the feces.
      Schistosoma mansoni worm pairs laid approximately 350 eggs per day with no change
      in the apparent rate of egg laying between eight and 52 weeks after infection and
      approximately one-third of the eggs were passed in the feces. Schistosoma
      japonicum worm pairs laid approximately 2,200 eggs per day initially and this
      decreased to 1,000 eggs per day by the end of the experiment, with one-third to
      one-half of the eggs being passed in the feces. There was marked variability in
      the fecundity of individual worm pairs, but the number of eggs passed in the
      feces of individual mice correlated well with the number of eggs in the
      intestines at all time points in S. mansoni-infected mice and at the seventh and
      tenth week of S. japonicum infection.

PMID- 8147488
TI  - A general classification of New World Leishmania using numerical zymotaxonomy.
AB  - More than 250 strains of Leishmania isolated from different localities and hosts
      in the New World were analyzed by enzyme electrophoresis, and their
      electromorphic profiles were compared with 19 reference strains representing most
      of the described species of this parasite. The 18 enzymic loci analyzed were very
      polymorphic, and the strains were classified into 44 zymodemes, each grouping
      strains with the same enzyme profiles. Each zymodeme was considered as an
      elementary taxon and the phenetic and phylogenetic relationships were determined
      by agglomerative hierarchical, ordination, and cladistic techniques. The
      different classification methods produced very similar results. The 44 zymodemes
      could be clustered into two groups, corresponding to the subgenera Leishmania and
      Viannia, by the numerical methods. The subgenus Viannia was shown to be
      monophyletic and could be further divided into species complexes representing L.
      braziliensis, L. naiffi, and L. guyanensis/L. panamensis/L. shawi, as well as
      some isolated taxa including L. lainsoni. The subgenus Leishmania, on the other
      hand, was polyphyletic, with New World isolates related to L. major clustered
      separately from the L. mexicana species complex. Most of the other zymodemes in
      this group represented independent taxa. The results confirm Viannia as a valid
      taxon but suggest that the status of the subgenus Leishmania should be further
      investigated. Leishmania braziliensis and L. naiffi were shown to be the most
      polymorphic species, while L. guyanensis, in spite of being the most common
      species found in this study, was remarkably homogeneous. The only variants were
      found south of the Amazon river. North of this river, the species was
      monomorphic.

PMID- 8147489
TI  - Synthetic DNA probes to identify members of the Anopheles gambiae complex and to
      distinguish the two major vectors of malaria within the complex, An. gambiae s.s.
      and An. arabiensis.
AB  - Two cloned DNA sequences, lambda C10 and lambda G12, have been isolated from a
      female Anopheles gambiae sensu stricto genomic DNA library in lambda EMBL4. The
      lambda C10 clone hybridized with equal intensity to all five of the six species
      in the An. gambiae Giles complex tested and was therefore suitable for use as a
      complex-specific clone. The lambda G12 clone was selected for its ability to
      distinguish the two major vectors of malaria within the complex, An. gambiae s.s.
      and An. arabiensis. Use of libraries consisting of only female DNA prevented the
      isolation of male-specific sequences. Southern blot analysis of the cloned DNA
      permitted the development of smaller Alu I subclones suitable for sequencing that
      still retained the original specificities and sensitivities of lambda C10 and
      lambda G12. Each clone was found to possess a series of repeated sequences in
      direct tandem array of 92-94 and 68 bases, respectively. A comparison of a number
      of copies of each of the repetitive sequences within the Alu I subclones enabled
      the definition of consensus sequences for the repetitive elements in lambda C10
      and lambda G12. Based on these consensus sequences, two oligonucleotides of 21
      and 23 bases designated pAngsl and pAngss were derived from lambda C10 and lambda
      G12, respectively. When tested as probes against DNA dot-blots and squash-blots
      of mosquito specimens, each oligonucleotide retained the same species specificity
      as the original clones from which they were derived. The nonradioactive, alkaline
      phosphatase-labeled pAngsl was able to detect as little as 1 ng of target genomic
      DNA by chemiluminescent detection in a 5-hr autoradiographic exposure. The pAngss
      probe could detect 5-10 ng of genomic DNA in similar assays. The new probes
      exhibit great potential for use in An. gambiae complex species identification
      because they provide both a means of distinguishing the two major vectors of
      malaria within the complex and of assessing the quality of squashed mosquito
      samples by providing a means of standardizing hybridization results.

PMID- 8147490
TI  - Dengue type-2 virus envelope protein made using recombinant baculovirus protects
      mice against virus challenge.
AB  - The gene coding for the envelope (E) glycoprotein of dengue-2 virus was cloned
      into baculovirus (Autographa californica nuclear polyhedrosis virus). The
      recombinant virus contained the entire E protein gene, preceded by 38 nucleotides
      from the end of the prematrix glycoprotein gene and followed by the first 83
      nucleotides of nonstructural protein 1. When expressed in Spodoptera frugiperda
      (Sf9) cells, approximately 1 mg of recombinant E antigen was made per 10(9)
      cells. This antigen reacted with polyclonal, anti-dengue type-2 antibody and a
      dengue type-2-specific, neutralizing monoclonal antibody. BALB/c mice immunized
      with the recombinant antigen produced only non-neutralizing antibody against
      dengue-2 virus, but were partially protected against morbidity and mortality
      after intracranial challenge with virulent dengue-2 virus.

PMID- 8147491
TI  - Antibody response to Plasmodium vivax antigens in human malaria.
AB  - The present study investigated the serum antibody response to parasite antigens
      involved in human Plasmodium vivax malaria. Analysis was performed by protein
      immunoblotting of a pool of P. vivax preparations obtained from blood of patients
      from Tapachula, Chiapas (southeastern Mexico), and sera from local malarious
      patients. Patient sera recognized 19 P. vivax antigens with molecular sizes
      between 17 and 170 kD. The most frequently recognized antigens were proteins of
      19, 31, 43, 72, 93, and 97 kD. These proteins could be useful in diagnostic
      methods and possibly relevant in vaccine design.

PMID- 8147492
TI  - Ivermectin treatment of bancroftian filariasis in Recife, Brazil.
AB  - To determine the effectiveness of single oral dosages of ivermectin ranging
      between 20 and 200 micrograms/kg and to make detailed observations of both the
      kinetics of parasite killing and the adverse reactions induced by treatment, the
      present double-blind study on ivermectin treatment of lymphatic filariasis caused
      by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife,
      Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-,
      and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means
      of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly
      fever, headache, weakness, and myalgia) occurred to some degree in almost all
      patients but generally lasted only 24-48 hr and were easily managed
      symptomatically. Adverse reactions were significantly milder in those receiving
      the lowest (20 micrograms/kg) ivermectin dose, and they were significantly
      correlated with individuals' pretreatment microfilaremia levels in all groups.
      Posttreatment eosinophilia was a regular feature of the response to treatment,
      with the magnitude and kinetics also proportional to pretreatment microfilarial
      levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme
      elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment,
      but all cleared without significant complications. The results indicate that W.
      bancrofti from Brazil is similar to strains of the parasites studied elsewhere in
      susceptibility to ivermectin, that the drug's systemic adverse reactions are
      essentially those resulting from parasite clearance, and that the intensity of
      these reactions can be significantly reduced by using the low (20 micrograms/kg)
      dose of ivermectin. This detailed dose-finding study provides information
      necessary for developing optimal regimens to treat bancroftian filariasis with
      ivermectin either alone or in combination with other medications.

PMID- 8147493
TI  - Intraocular fascioliasis: a case report.
AB  - We report the case of a 28-year-old male who had been ill with headache and motor
      weakness for a month and developed sudden pain and blindness of the right eye.
      During ophthalmoscopy, a worm was recognized penetrating the iris, occupying the
      anterior chamber for a brief period, returning back behind the iris, and leaving
      corneal edema with hyphyema. Enucleation was performed to prevent the worm's
      escape from the eye. The enucleated eye revealed areas of a focal degeneration of
      sclera and intraocular hemorrhage. Microscopic findings of an abrupt tissue
      defect and few inflammatory reactions in the uvea suggested very recent migration
      of a moving worm. The flatworm detected in the anterior chamber was identified to
      be a juvenile Fasciola sp. This case is presumed to be the first case of
      intraocular fascioliasis reported in the literature.

PMID- 8147494
TI  - Field trial of an outer surface protein A (OspA) antigen-capture enzyme-linked
      immunosorbent assay (ELISA) to detect Borrelia burgdorferi in Ixodes scapularis.
AB  - Field-collected adult male Ixodes scapularis from Westchester County, New York
      were bisected and Borrelia burgdorferi infection rates were ascertained by both a
      direct fluorescent antibody test and an outer surface protein A (OspA) antigen
      capture enzyme-linked immunosorbent assay (ELISA). Both assays gave identical
      antigen positivity rates with 89% concordance between the two assays. Storing
      dried ticks before ELISA analysis had no significant effect on the ability of the
      ELISA to determine the presence of OspA compared with assaying live ticks. The
      OspA antigen positivity rate for dried ticks was 49% compared with 53% for live
      ticks, with mean OspA antigen spirochete equivalents of 3,388 and 2,823 for dried
      and live ticks, respectively.

PMID- 8147495
TI  - Antigen-capture enzyme immunoassay: a comparison with other methods for the
      detection of spotted fever group rickettsiae in ticks.
AB  - To evaluate the prevalence of spotted fever group rickettsiae along the Adriatic
      Coast of Croatia, 832 ticks were examined by hemolymph test, direct
      immunofluorescence, antigen-capture enzyme immunoassay, and polymerase chain
      reaction. Very good agreement was observed among direct immunofluorescence,
      polymerase chain reaction, and antigen-capture enzyme immunoassay. Twelve ticks
      that were positive by hemolymph test and negative by both direct
      immunofluorescence and polymerase chain reaction presumably do not represent
      spotted fever group rickettsiae. By direct immunofluorescence, spotted fever
      group rickettsiae were present in 12% of Rhipicephalus bursa, 10.6% of Rh.
      sanguineus, and 7.8% of Dermacentor marginatus. From the 98 ticks containing
      rickettsia-like organisms by hemolymph test, seven spotted fever group
      rickettsial isolates were established in cell culture. Four isolates were
      identified as Rickettsia conorii. The antigen-capture enzyme immunoassay, which
      utilizes a monoclonal antibody to antigens of the 135-kD surface protein shared
      among many members of the spotted fever group, is recommended for primary
      screening of tick samples because it is reliable and yet less labor-intensive
      than the hemolymph and direct immunofluorescence tests. Although the polymerase
      chain reaction is too expensive for use as a screening method, it is recommended
      for confirmation of positive screening results. In addition to the technologic
      advance of the antigen-capture enzyme immunoassay, this study documented by
      contemporary methods that R. conorii is present along the eastern Adriatic Coast
      not only in the classic vector, Rh. sanguineus, but also in Rh. bursa and D.
      marginatus.

PMID- 8147496
TI  - Prevalence of lymphocytic choriomeningitis virus infection in a human population
      of Argentina.
AB  - The activity of lymphocytic choriomeningitis virus (LCMV) in the endemic area of
      Argentine hemorrhagic fever has been previously reported and represents the first
      evidence of the coexistence of two arenaviruses pathogenic for humans, Junin and
      LCMV, in the same geographic area. Data are presented on the prevalence of LCMV
      human infection in a 10,000-km2 area located in Santa Fe Province, Argentina.
      Study subjects were males, 15-65 years old, living and/or working in the rural
      area of 41 localities. One serum sample was obtained from each 7,227 volunteers
      from a total population of 21,340 individuals with the described features.
      Antibodies to LCMV were assessed by means of an indirect immunofluorescence
      assay. These antibodies were found in 172 serum samples, with titers ranging from
      1:8 to 1:128 (geometric mean titer = 15.03), and a mean percentage of infection
      of 2.38%. A significantly different distribution of positive individuals was
      found between the eastern (1.54%) and western (3.07%) borders of the region
      studied (P < 0.0003). The higher percentage of infection on the western side was
      due to the existence of two clusters of counties with a mean percentage of 6.06%
      that was significantly different from the 1.67% obtained in the rest of the study
      area (P < 0.0003). These results provide new information on the LCMV activity in
      Argentina, and update the evidence on the coexistence of two arenaviruses in the
      same region of Argentina. This circumstance increases the probability of
      generation of viral reassortants with changes that could determine the need for
      new therapeutic and/or preventive strategies for arenaviral diseases.

PMID- 8147497
TI  - Epidemiologic aspects of a St. Louis encephalitis outbreak in Fort Walton Beach,
      Florida in 1980.
AB  - From July 10 through August 4, 1980, five cases of St. Louis encephalitis (SLE)
      occurred in and near Fort Walton Beach on the Gulf Coast of northwest Florida.
      These were the first cases of SLE ever reported from the Florida panhandle. To
      determine the extent of SLE infection in the community, sera (n = 968) were
      collected from patients at the local hospital and county public health unit and
      tested for SLE virus antibody. The SLE attack rate was highest in a centrally
      located impoverished census tract. There was a trend toward decreasing
      seroprevalence with distance from the central area of the city. Overall,
      seroprevalence was higher in males (prevalence ratio = 2.7) and in all areas,
      seroprevalence increased with age. The serosurvey results suggest that SLE has
      been endemic in the Fort Walton Beach area.

PMID- 8147498
TI  - Neurological examination of the newborn.
AB  - Sophisticated technology for neurodiagnosis supplements, but does not replace,
      the neurological examination. Physical examination remains the standard for
      assessing the normal or abnormal function of the nervous system, the localization
      of neurological injury, and the severity of impairment. An experienced examiner
      can rapidly perform this assessment and then exercise the best judgement in
      selecting laboratory investigations.

PMID- 8147499
TI  - Pontocerebellar hypoplasias. An overview of a group of inherited
      neurodegenerative disorders with fetal onset.
AB  - Cerebellar hypoplasia is common to a variety of congenital disorders. Both stable
      conditions and progressive (degenerative) disorders may cause cerebellar
      hypoplasia. Pontocerebellar hypoplasia (PCH) is distinct from cerebellar
      hypoplasias in general, because the ventral pons is affected. Reviewing both
      clinical and neuropathological evidence, two specific neurogenetic entities are
      delineated. It is proposed to call these, respectively, type 1 (PCH-1) and type 2
      (PCH-2). In type 1 the hallmark is the presence of spinal anterior horn
      degeneration similar to Werdnig-Hoffmann disease. Presentation in the neonatal
      period is characterized by respiratory insufficiency, frequent congenital
      contractures, and a combination of central and peripheral motor signs. Patients
      die early, usually before 1 year of age. In type 2 the hallmark is the presence
      of chorea/dystonia, which is often severe, while spinal anterior horn pathology
      is absent. Patients have microcephaly and severely impaired mental and motor
      development. They frequently die during childhood. Neuronal degeneration in both
      types of PCH is non-specific. Reactive changes in the degenerated parts appear
      more extensive in type 1. Examples of both types are given. Differentiation of
      the two types appears straightforward and possible by clinical means.
      Carbohydrate-deficient glycoprotein syndrome, one other cause of
      (ponto)cerebellar hypoplasia, should be excluded in all cases of PCH by
      appropriate means.

PMID- 8147500
TI  - Recent advances in non-invasive studies of higher brain functions.
AB  - Recent advances in modern technologies have enabled us to investigate higher
      brain functions non-invasively in human subjects. These techniques include
      topographic analysis of the scalp-recorded electric potentials, recording of the
      magnetic field generated from the brain, measurement of regional cerebral blood
      flow changes in association with various forms of activation (activation study),
      measurement of regional cerebral glucose metabolism, transcranial magnetic
      stimulation of cortical areas, measurement of chemical change in the brain in
      association with functional conditions by the use of magnetic resonance (MR)
      spectroscopy, and dynamic functional MR imaging.

PMID- 8147501
TI  - The cognitive development of children born preterm and affected by spastic
      diplegia.
AB  - In a prospective study the intellectual development of 20 premature children
      affected by spastic diplegia was compared with that of 10 preterm low-risk
      children. The assessment was carried out with the Griffiths scale at the age of 3
      years and with the WPPSI scale at the age of 6 years. The analysis of data
      collected in the 2 psychometric evaluations of the preterm-born diplegic children
      showed a disharmonic profile of neuropsychological functions, already present at
      the age of 3 years and confirmed at the age of 6 years. The average scores in
      diplegic children were poorest in the subscales locomotor, eye-hand coordination,
      and performance on Griffiths scale, and in the performance subtests of the WPPSI
      scale. The mean scores of subscales for hearing and speech, and practical
      reasoning on the Griffiths scale and of the verbal subscale of the WPPSI were
      near to the lower range of the normal distribution. Significant differences in
      performance subtests were found between the groups of preterm diplegic children
      and the group of low-risk preterm children, both at 3 and 6 years of age.

PMID- 8147502
TI  - Evaluation of myelination by means of the T2 value on magnetic resonance imaging.
AB  - The progress of myelination in the cerebrum was evaluated by visual inspection,
      and magnetic resonance (MR) imaging and the transverse relaxation time (T2) was
      calculated from double echo images. Twenty-three pediatric cases, who did not
      show intracranial organic changes on MR examination, were included. The T2 values
      in the corpus callosum (CC), frontal deep white matter (FWM), occipital deep
      white matter (OWM) and centrum semiovale (CS) were calculated, and the changes in
      these values with age were followed. During the first year of life, a rapid
      decrease in the T2 value was seen, followed by a more gradual decrease. The T2
      value seemed to reach the adult level between 2 and 3 years of life in all areas
      examined. The T2 values between 2 and 16 years in CC, FWM, OWM and CS were 59.7
      +/- 3.6, 64.5 +/- 5.2, 69.8 +/- 4.8 and 66.3 +/- 3.3 ms (mean +/- S.D.),
      respectively. The T2 values in patients with clinically diagnosed Pelizaeus
      Merzbacher disease (PMD) and late onset Krabbe disease were also calculated. In
      PMD, non-progressive prolongation of the T2 value was observed in all areas. In
      late onset Krabbe disease, on the other hand, progressive prolongation of the T2
      values was mainly demonstrated in OWM and the posterior part of CS. These results
      suggest that the T2 value in the cerebral white matter allows more objective
      judgement than visual inspection, and makes it possible to clarify the mechanism
      underlying abnormal myelination, i.e. progressive or not.

PMID- 8147503
TI  - Autosomal recessive congenital cerebellar atrophy. A clinical and
      neuropsychological study.
AB  - Congenital cerebellar atrophy associated with a non-progressive cerebellar
      syndrome and mild cognitive retardation is described in seven cases, four of them
      familial. Their occurrence is consistent with an autosomal recessive inheritance.
      Clinical and neuroimaging data seem to exclude supratentorial changes. Even
      though it is not possible to definitely rule out a possible role of the forebrain
      in determining the mental defect, the neuropsychological study supplies arguments
      stressing the relationship between cerebellar defect and cognitive development.

PMID- 8147504
TI  - Weber syndrome caused by intracerebral hemorrhage in a hemophiliac boy.
AB  - A rare occurrence of the Weber syndrome in childhood is reported. The patient was
      a 7-year-old hemophiliac with recurrent intracerebral bleeding into the right
      cerebral peduncle and pontine base. Left hemiparesis involving the face and
      tongue developed and was later accompanied by right oculomotor nerve palsy.

PMID- 8147505
TI  - A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme
      deficiency but detectable enzyme protein. Comparison of two cases of Zellweger
      syndrome.
AB  - Three infants with peroxisomal disorders were investigated clinicobiochemically
      and neuroradiologically. Two had classical Zellweger syndrome, and cranial CT
      scans showed typical disproportionate enlargement of the occipital horns of the
      lateral ventricles (colpocephaly) with marked hypodensity of the white matter. In
      one female infant, although the clinical findings were similar to those in
      Zellweger syndrome, some findings, such as elevated transaminase levels, liver
      fibrosis, the absence of renal cortical cysts and colpocephaly, were negative or
      milder. Biochemical analyses revealed increased very long-chain fatty acids,
      dicarboxylic aciduria and impaired beta-oxidation of lignoceric acid. However,
      peroxisomes were abundantly present in hepatocytes and cultured fibroblasts, and
      all peroxisomal beta-oxidation enzyme proteins were detected on immunoblot
      analysis. A cell fusion study suggested that the enzyme responsible for this case
      of 'pseudo-Zellweger syndrome' is bifunctional.

PMID- 8147506
TI  - Subdural hematoma and glutaric aciduria type 1.

PMID- 8147507
TI  - What changes drug metabolism in critically ill patients? Two preliminary studies
      in isolated human hepatocytes.
AB  - The metabolism of many drugs is abnormal in the critically ill patient. The
      causes of this are unknown, and investigation in patients is difficult. We
      therefore used isolated, cultured human hepatocytes to study the effects of
      hypoxia and induction on cytochrome P450 3A, the cytochrome responsible for the
      metabolism of many drugs. When hepatocytes were exposed to 5% oxygen, the amount
      of 3A produced, after induction with rifampicin, was five to 10 times less than
      the amount produced in 21% oxygen. In another study, we exposed isolated
      hepatocytes for 4 days to serum from five critically ill patients or from
      volunteers. At the end of this time, the functional ability of the hepatocytes to
      glucuronidate 14C progesterone was measured. Four of the five patients had a
      substance in their plasma that reduced the ability of the hepatocytes to
      glucuronidate progesterone. The nature of this substance and the reason that the
      serum from the fifth patient did not affect metabolism are unknown. This model is
      able to simulate the abnormalities which occur in critically ill patients.
      Further studies are needed to explain our observations and to identify the
      substances in the serum from critically ill patients that alter drug metabolism.

PMID- 8147508
TI  - A cost-utility analysis of intensive therapy. II: Quality of life in survivors.
AB  - A questionnaire designed to assess changes in quality of life was sent to 56
      survivors of critical illness one year after their admission to an intensive
      therapy unit. Forty-one patients completed the questionnaire, and for the
      majority, quality of life remained unchanged (n = 25). However significant
      decreases in quality of life were found in those patients who previously enjoyed
      a good quality of life or were admitted with respiratory problems. Survivors also
      recorded significant decreases in five aspects of their perceived quality of life
      (ability to think and remember, seeing family, their contribution to society,
      activities outside work and income). As part of a previous study, the costs
      incurred by each of these patients had been measured so that changes in quality
      of life detected in this study could be combined to the individual costs and
      expressed as cost per quality adjusted life year. The cost of intensive therapy
      for a patient surviving for one year after acute respiratory or cardiovascular
      disease was 2600 pounds. The total hospital cost per quality adjusted life year
      was estimated at 7500 pounds, which places intensive therapy at the higher end of
      health programme costs. If the costs of nonsurvivors are included in the cost per
      quality adjusted life year calculation, the cost of intensive care increases
      considerably.

PMID- 8147509
TI  - The respiratory depressant effect of morphine. A comparative study in three
      ethnic groups.
AB  - The respiratory response to carbon dioxide was measured in 130 ASA 1 adult male
      patients from three ethnic groups, European, Nepalese, and Chinese, both before
      and after premedication with intramuscular morphine sulphate (200 micrograms.kg-1
      body weight). Satisfactory results were obtained from 125 patients. Overall,
      there was no ethnic difference in the effect of morphine on the respiratory
      response to carbon dioxide, but initially the Chinese group appeared to be more
      sensitive in their response to carbon dioxide than the Europeans and Nepalese.
      However, there was a significant correlation between respiratory response to
      carbon dioxide and pulse rate and on restricting analysis to those patients with
      a pulse rate equal to or less than 72 beat.min-1, the ethnic difference in carbon
      dioxide response disappeared. It was concluded that there were no ethnic
      differences in the respiratory response to carbon dioxide before or after
      morphine in male Europeans, Nepalese and Chinese but that the respiratory
      response to carbon dioxide may be influenced by long term physical training.

PMID- 8147510
TI  - Neutral head position for placement of internal jugular vein catheters.
AB  - A new approach to the internal jugular vein is described which keeps the head and
      neck in the neutral position and uses bony and cartilaginous landmarks for
      guidelines. Venous puncture is made along an axial line drawn superiorly from the
      lateral edge of the bony depression caused by the insertion of the
      sternocleidomastoid muscle on the superior edge of the clavicle. This line, at
      the level of the cricoid cartilage, lies directly over the internal jugular vein.
      In 55 patients initially studied, the mean (SEM) number of puncture attempts to
      locate the vein was 1.4 (0.2) per patient, with an overall success rate of 98%.
      In 84%, the internal jugular vein was located exactly where predicted, the others
      were just lateral to the point. The complication rate (all short-term) was 3.6%.
      Subsequently the internal jugular vein was cannulated successfully using the
      developed technique in 20 consecutive trauma patients with suspected cervical
      instability. An average of 1.2 (0.2) (range 1-3) attempts were made per patient
      to locate the vein and there were no complications. We propose this technique as
      a safe and reliable method of gaining central venous access in patients with
      possible cervical spine injury following trauma.

PMID- 8147511
TI  - The intensity of postoperative shivering is unrelated to axillary temperature.
AB  - The relationship between axillary temperature and postoperative shivering was
      examined in 302 patients who entered one recovery room in the Derbyshire Royal
      Infirmary over a one-month period. No relationship was found between temperature
      and the occurrence of shivering, or between conscious level and the occurrence of
      shivering.

PMID- 8147512
TI  - Measurement of intercostal and pleural pressures by epidural catheter.
AB  - The pressures in the intercostal and interpleural spaces were measured in 20
      patients using an 18 gauge epidural catheter to confirm accurate catheter
      positioning for continuous intercostal and interpleural local anaesthetic
      blockade. In the intercostal space the mean (SD) pressure was negative (-1.8
      (0.3)) mmHg and positive (+2.1 (0.3)) mmHg at the end of inspiration and
      expiration respectively. In contrast, in the interpleural space although the
      pressure varied with the respiratory cycle it remained negative both at the end
      of inspiration (-8.3 (1.0)) mmHg and expiration (-2.1 (0.8)) mmHg. We conclude
      that measurement of intercostal and interpleural pressures with an epidural
      catheter is a straightforward procedure which may be helpful in confirming
      accurate catheter placement for continuous intercostal or interpleural local
      anaesthetic blockade.

PMID- 8147513
TI  - Quality of life after multiple trauma requiring intensive care.
AB  - A prospective observational study using structured interviews was used to assess
      changes in quality of life experienced by surviving trauma victims after
      management on a general intensive therapy unit in a district general hospital.
      Each patient's age, distribution of injuries, severity of illness on admission
      and duration of management were recorded. Deaths in the study group were excluded
      by examining the Hospital's 'Patient Administrative System'. Three attempts were
      then made to contact all known survivors and to assess their quality of life
      using three previously recognised and validated methods. Eighty-three survivors
      of multiple trauma were discharged but 19 were not studied. Of the remaining 64,
      42 patients completed the questionnaire. After multiple trauma, patients reported
      significant decreases in their quality of life in relation to their overall
      health, happiness, ability to think and to pursue leisure activities, their
      income and their employment. Their mean Perceived Quality of Life Score decreased
      by 13% (95% confidence intervals 7.5-19.5%). Sixty-two percent of survivors
      experienced severe social disability and a modest or severe impairment at work.
      The Nottingham Health Profile identified major changes in 'psychological' aspects
      of quality of life, namely energy and emotional reactions.

PMID- 8147514
TI  - Air in the cavernous sinus following scalp vein cannulation.
AB  - A 7-month-old infant was found to have air in the cavernous sinus during a CT
      scan under general anaesthesia. An anterior scalp vein had been used to
      administer atracurium and contrast. The anatomy and precautions to prevent air
      embolism during scalp vein cannulation are discussed.

PMID- 8147515
TI  - Cerebrospinal fluid cutaneous fistula. An unusual complication of epidural
      anaesthesia.
AB  - We describe two cases of cerebrospinal fluid-cutaneous fistula following epidural
      anaesthesia used for postoperative pain relief. In each case spinal headache
      occurred only after removal of the catheters and both patients were treated
      successfully with autologous blood patches.

PMID- 8147516
TI  - Flow characteristics of long spinal needles.
AB  - A 120 mm, 27-gauge needle has recently been introduced for subarachnoid
      anaesthesia when using a single-space, combined spinal-extradural technique. The
      flow characteristics of this needle were compared with those of a 120 mm, 26
      gauge needle using a pressure monitor infusion pump. Surprisingly, the resistance
      to fluid flow of the 26-gauge needle was twice that of the 27-gauge needle. The
      results of this experiment were confirmed by the findings of a clinical study
      undertaken in 100 obstetric patients who required regional anaesthesia. The time
      taken from dural puncture to appearance of cerebrospinal fluid at the hub of the
      needle was on average three times greater with the 26-gauge needle.

PMID- 8147517
TI  - A simple central venous puncture detector.
AB  - During central venous cannulation, percutaneous venous puncture is performed
      blindly using a variety of surface landmarks on the body for different puncture
      sites. To avoid vessel transfixion and injury to adjacent structures, the
      earliest detection of venous puncture is essential. A simple central venous
      puncture detector is described, which not only efficiently detects entry of the
      needle into the vein but also prevents air embolism and blood spillage.

PMID- 8147518
TI  - The relationship between oxygen delivery and uptake in the critically ill: is
      there a critical or optimal therapeutic value? A meta-analysis.
AB  - In order to identify a critical or an optimal therapeutic value for oxygen
      delivery and oxygen uptake, we analysed data from 40 publications concerning the
      relationship between oxygen delivery and consumption in patients with adult
      respiratory distress syndrome, trauma or during sepsis, and in nonseptic
      controls. According to the outcome, the patients were allocated to either group 1
      (survivors) or group 2 (nonsurvivors). While oxygen delivery and uptake (mean,
      SEM) were significantly higher in patients with adult respiratory distress
      syndrome (636, SEM 31 ml.min-1.m-2 and 155, SEM 5 ml.min-1.m-2), trauma (782, SEM
      77 ml.min-1.m-2 and 167, SEM 10 ml.min-1.m-2) and sepsis (654, SEM 28 ml.min-1.m
      2 and 163, SEM 5 ml.min-1.m-2) than in nonseptic controls (452, SEM 18 ml.min-1.m
      2 and 126, SEM 3 ml.min-1.m-2, p < 0.05), there were no significant differences
      in these parameters between survivors and nonsurvivors. Although therapeutic
      manoeuvres were effective in increasing both oxygen delivery and consumption,
      these improvements were not paralleled by an increase in survival rate. The
      correlation between oxygen delivery and uptake is generally a result of the use
      of pooled data and therefore prone to mathematical coupling. This is true
      particularly for patients with adult respiratory distress syndrome and sepsis.
      Thus, our study failed to identify either an optimal or a critical value of
      oxygen delivery or oxygen consumption in critically ill patients.

PMID- 8147519
TI  - Mortality after spinal and general anaesthesia for surgical fixation of hip
      fractures.
AB  - One thousand, three hundred and thirty three patients who underwent anaesthesia
      for surgical fixation of a hip fracture were studied prospectively to assess the
      effects on outcome of general and spinal anaesthesia. There were no significant
      differences between the groups in risk factors, length of hospital stay or
      mortality rates after 30 days or one year. The data presented may be useful for
      those wishing to audit anaesthetic services provided to patients with hip
      fracture.

PMID- 8147520
TI  - A comparison of patient and anaesthetist controlled midazolam sedation for dental
      surgery.
AB  - Thirty healthy Hong Kong Chinese patients between the ages of 15 and 31 years
      with bilaterally impacted lower third molar teeth, scheduled for surgical removal
      were studied. All the patients presented twice (for the right and left sides) and
      received, on separate occasions, patient or anaesthetist-controlled midazolam
      sedation allocated using a randomised, crossover design. Both techniques provided
      reliable sedation with verbal contact maintained, minimal changes in respiratory
      and cardiovascular function, good operating conditions and a high degree of
      patient satisfaction. The majority of patients (67%) thought they could sedate
      themselves better on a subsequent visit and were confident that they could do
      this more satisfactorily than the anaesthetist. An almost equal number preferred
      patient (n = 12) or anaesthetist (n = 13) controlled sedation, with the remainder
      having no preference. The total dose of midazolam was very similar in the two
      groups, 5.3 (SD 2.4) mg and 5.0 (SD 1.1) mg for patient and anaesthetist
      controlled sedation respectively.

PMID- 8147521
TI  - Magnesium flux and cardiac surgery. A study of the relationship between magnesium
      exchange, serum magnesium levels and postoperative arrhythmias.
AB  - A prospective study of 128 adult cardiac surgical patients was undertaken in
      order to quantify net magnesium loss and its relationship to serum magnesium
      levels and postoperative problems, particularly arrhythmias. Peri-operative
      magnesium flux on the first day was calculated from the administered magnesium
      (in cardioplegia solution and intravenous infusion) and urinary magnesium loss.
      Magnesium input ranged from 24 mmol to 40 mmol, resulting in a net magnesium gain
      in 94% of patients. Hypomagnesaemia, identified in 34% of patients pre
      operatively and 30% of patients postoperatively, had no significant correlation
      with the measured peri-operative magnesium flux or the electrocardiograph
      corrected-QT interval. Fifty-three patients developed postoperative arrhythmias,
      but there was no significant correlation with the serum total magnesium
      concentration, or with the peri-operative change in serum magnesium level,
      magnesium flux, or QT interval. The data suggest that serum total magnesium is
      not a useful measurement upon which to base preventive or therapeutic measures in
      cardiac surgical patients.

PMID- 8147522
TI  - Sleeping positions adopted by pregnant women of more than 30 weeks gestation.
AB  - The position adopted during sleep by 52 pregnant women and 31 age-matched
      nonpregnant control subjects was studied. The pregnant group were all beyond the
      30th week of gestation. In the pregnant group, 40 (77%) adopted a left tilt, 11
      (21%) a right tilt and one (2%) was supine. In the control group, eight (26%)
      adopted a left tilt, 10 (32%) a right tilt, 12 (39%) were supine and one (3%) was
      prone. Closer analysis of the position adopted by the pregnant group showed: 33
      adopted a full left 90 degrees tilt, five a left 60 degrees tilt, two a left 30
      degrees tilt, 11 adopted a full 90 degrees right tilt and only one was supine.
      There was a significant difference between the sleeping positions of the pregnant
      and the control groups (p < 0.001). The majority of the pregnant group adopted a
      sleeping position that reduced the likelihood of aortocaval compression syndrome.

PMID- 8147523
TI  - A comparative study of the incidence of sore throat with the laryngeal mask
      airway.
AB  - In a prospective study of 150 patients randomly assigned to three groups, we have
      compared the incidence and duration of sore throat after a standard anaesthetic
      regimen using three different methods of airway management: facemask; laryngeal
      mask, and laryngeal mask with insertion aid. The insertion aid is currently being
      developed by Portex Ltd and is intended both to facilitate accurate placement of
      the laryngeal mask and to reduce trauma during insertion. All the patients were
      women undergoing short operative procedures requiring minimal postoperative
      analgesia. The incidence of sore throat was significantly less with a facemask
      (8%) than with the laryngeal mask when used without the insertion aid (28.5%) (p
      < 0.02). When using the insertion aid the incidence was 18% and this was not
      statistically different from the facemask. The presence of blood on the laryngeal
      mask (22%) was less likely when the insertion aid was used (4%) (p < 0.02).

PMID- 8147524
TI  - Orotracheal intubation in a patient with cervical spine injury.

PMID- 8147525
TI  - Cardiorespiratory arrest following combined spinal epidural anaesthesia.

PMID- 8147526
TI  - Postpartum meningitis.

PMID- 8147527
TI  - Portable suction devices.

PMID- 8147528
TI  - Advancing atraumatic needles?

PMID- 8147529
TI  - Artefactual hypertension from rhythmic finger tapping.

PMID- 8147530
TI  - Anaphylactoid reaction following epidural block: local anaesthetic or latex?

PMID- 8147531
TI  - T-piece scavenging: simple alternatives.

PMID- 8147532
TI  - Avoiding calculations for preparing continuous infusions.

PMID- 8147533
TI  - Positioning fine-bore nasogastric tubes.

PMID- 8147534
TI  - A complication of laparoscopic hernia repair.

PMID- 8147535
TI  - Growth of micro-organisms in propofol.

PMID- 8147536
TI  - Postoperative transient hemihypaesthesia and severe headache associated with
      caffeine withdrawal.

PMID- 8147537
TI  - Adjustable paediatric breathing system support.

PMID- 8147538
TI  - Pre-operative visits--the 'printy' approach.

PMID- 8147539
TI  - Peri-operative presentation of an intracerebral tumour.

PMID- 8147540
TI  - Critical incident due to inappropriate resterilisation.

PMID- 8147541
TI  - The performance of two intensive care humidifiers at high gas flows.

PMID- 8147542
TI  - Faulty epidural needle.

PMID- 8147543
TI  - Another cause for failed epidural.

PMID- 8147545
TI  - Human ehrlichiosis in adults after tick exposure. Diagnosis using polymerase
      chain reaction.
AB  - OBJECTIVE: To identify and prospectively follow patients with suspected human
      ehrlichiosis regarding clinical manifestations, laboratory variables, methods for
      confirming the diagnosis, and complications. DESIGN: Prospective case study.
      SETTING: University and Veterans Affairs hospital and clinics. PATIENTS:
      Observations in 30 adult patients with acute febrile illness or with unexplained
      fevers and cytopenias or abnormal liver profiles or both. MEASUREMENTS: Serial
      clinical examinations, hematologic profiles, liver profiles, electrolyte
      determinations, chest radiographs, and response to therapy; other studies
      appropriate for patient care. INTERVENTION: Therapy with doxycycline. RESULTS:
      Thirty cases of ehrlichiosis were identified between 1989 and 1992. Tick exposure
      was strongly associated with the illness (P = 0.0001). Symptoms were nonspecific;
      fever, chills, and headache predominated but many other symptoms also occurred.
      Fever and skin rashes with various morphologic characteristics were the most
      common physical findings. Laboratory investigations indicate that the
      hematologic, hepatic, and central nervous systems are commonly involved in human
      ehrlichiosis. Twenty of 23 patients (87%) tested by the polymerase chain reaction
      using Ehrlichia chaffeensis sequences and whole blood samples were positive for
      E. chaffeensis. CONCLUSIONS: The syndrome of human ehrlichiosis is not commonly
      recognized by physicians. Ehrlichiosis should be considered in the differential
      diagnosis of patients with febrile illness after known or possible tick exposure,
      particularly if accompanying cytopenias or abnormal liver profiles or both are
      present. The therapeutic response to doxycycline is prompt, and complications are
      uncommon in promptly treated patients. The polymerase chain reaction applied to
      whole blood samples is a promising test for rapid confirmation of the diagnosis
      within 24 to 48 hours.

PMID- 8147544
TI  - A case-management system for coronary risk factor modification after acute
      myocardial infarction.
AB  - OBJECTIVE: To evaluate the efficacy of a physician-directed, nurse-managed, home
      based case-management system for coronary risk factor modification. DESIGN:
      Randomized clinical trial in which patients received a special intervention (n =
      293) or usual medical care (n = 292) during the first year after acute myocardial
      infarction. SETTING: 5 Kaiser Permanente Medical Centers in the San Francisco Bay
      area. PATIENTS: 585 men and women aged 70 years or younger who were hospitalized
      for acute myocardial infarction. INTERVENTION: In the hospital, specially trained
      nurses initiated interventions for smoking cessation, exercise training, and diet
      drug therapy for hyperlipidemia. Intervention after discharge was implemented
      primarily by telephone and mail contact with patients in their homes. All
      medically eligible patients received exercise training; all smokers received the
      smoking cessation intervention; and all patients received dietary counseling and,
      if needed, lipid-lowering drug therapy. OUTCOME: Smoking prevalence and plasma
      low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months
      after infarction, and functional capacity was measured 6 months after infarction.
      RESULTS: In the special intervention and usual care groups, the cotinine
      confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL
      cholesterol levels were 2.77 +/- 0.69 mmol/L and 3.41 +/- 0.90 mmol/L (107 +/- 30
      mg/dL and 132 +/- 30 mg/dL) (P = 0.001), and functional capacities were 9.3 +/-
      2.4 METS and 8.4 +/- 2.5 METS (P = 0.001), respectively. CONCLUSION: In a large
      health maintenance organization, a case-management system was considerably more
      effective than usual medical care for modification of coronary risk factors after
      myocardial infarction.

PMID- 8147546
TI  - Human ehrlichiosis in the United States, 1985 to 1990.
AB  - OBJECTIVE: To describe the epidemiology, clinical features, laboratory
      manifestations, response to therapy, and factors related to morbidity and
      mortality in a large group of patients with ehrlichiosis. DESIGN: Case-series.
      SETTING: Laboratory-based surveillance in the United States. PATIENTS: 237
      patients whose serum had a fourfold increase or decrease in antibodies to
      Ehrlichia canis or E. chaffeensis. MEASUREMENTS: Epidemiologic, clinical,
      laboratory data, hospitalization, duration of illness, complications, and
      treatment response. RESULTS: From 1985 through 1990, 237 case-patients were
      identified in 21 states; rates exceeded 1 per 100,000 per year in only 5
      counties. Incidence rates increased with age and were higher among men. Most case
      patients had nonspecific illness and were not suspected of having a rickettsial
      infection. Many patients (60.8%) were hospitalized. Leukocyte and platelet counts
      typically decreased and liver function tests typically increased through day 7.
      Three (6.1%) of 49 outpatients treated only with tetracycline were hospitalized
      compared with 35 (92%) of 38 outpatients treated only with antibiotics other than
      tetracycline or chloramphenicol (P < 0.001). Among hospitalized patients,
      recovery was faster for those initially treated with tetracycline (median, 16
      days) or chloramphenicol (median, 12 days) than for those initially treated with
      other antibiotics (median, 27 days; P = 0.03 for both comparisons). In a logistic
      regression analysis, severe illness or death was more probable among case
      patients 60 years or older (odds ratio [OR], 4.60; 95% CI, 1.87 to 11.2) and
      among those who did not receive tetracycline or chloramphenicol until 8 or more
      days after symptom onset (OR, 4.38; CI, 1.36 to 14.0). CONCLUSIONS: The findings
      of this study are primarily representative of more seriously ill patients with
      human ehrlichiosis. Although rates are low, ehrlichiosis is found in many areas
      of the United States. Patients with a history of tick exposure, acute febrile
      illness, decreasing leukocyte counts, and decreasing platelet counts may have
      ehrlichiosis. Prompt treatment with tetracycline or chloramphenicol markedly
      decreases the morbidity.

PMID- 8147547
TI  - Effect of postoperative low-dose dopamine on renal function after elective major
      vascular surgery.
AB  - OBJECTIVE: To determine the effect on renal function of postoperative low-dose
      dopamine in volume-replete patients after elective, major vascular abdominal
      surgery. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING:
      Intensive care unit of a referral hospital in Brisbane, Australia. PATIENTS: 37
      patients having elective repair of an abdominal aortic aneurysm or having
      aortobifemoral grafting; 18 received dopamine, and 19 received placebo. Two
      patients were excluded from the 5-day analysis because of perioperative death.
      INTERVENTIONS: Patients were randomly assigned to receive either placebo or a low
      dose infusion of dopamine (3 micrograms/kg per minute) in saline. Patients in
      both groups were given sufficient crystalloid to maintain a urine flow of more
      than 1 mL/kg per hour during the first 24 postoperative hours. Care in the
      intensive care unit was otherwise usual and was the same for each group.
      MEASUREMENTS: Plasma creatinine levels, urea levels, and creatinine clearance
      were measured preoperatively and postoperatively (at 24 hours and 5 days). Urine
      flow and the volume of crystalloid during the first 24 hours were recorded.
      RESULTS: Two postoperative deaths occurred in the dopamine group (from renal
      failure and myocardial infarction). Four patients had myocardial infarction,
      three of whom received dopamine. Plasma creatinine levels remained unchanged in
      both groups. At 24 hours, the mean plasma urea level decreased by 1.07 mmol/L in
      the dopamine group compared with 1.84 mmol/L in the placebo group, a difference
      of 0.77 (95% CI, -0.12 to 1.67). The mean 24-hour creatinine clearance increased
      by 0.165 mL/s (9.89 mL/min) in the dopamine group and by 0.199 mL/s (11.98
      mL/min) in the placebo group (P > 0.2). Urine volumes were slightly higher in
      those receiving dopamine (1.83 mL/kg compared with 1.6 mL/kg, a difference of
      0.23 [CI, -0.18 to 0.64]). None of these differences were statistically or
      clinically significant. CONCLUSIONS: Within the limits of the small size of the
      study, low-dose dopamine appeared to offer no advantage to euvolemic patients
      after elective abdominal aortic surgery. However, patients with acute oliguric
      renal failure were not included in the study.

PMID- 8147549
TI  - Use of inhaled nitric oxide to reverse flow through a patent foramen ovale during
      pulmonary embolism.

PMID- 8147548
TI  - Hepatitis C virus infection in spouses of patients with type C chronic liver
      disease.
AB  - OBJECTIVE: Survey for markers of hepatitis C virus (HCV) infection in spouses of
      patients with HCV-related chronic liver disease. DESIGN: Cross-sectional
      clinical, serologic, and molecular biological study of spouses of patients with
      HCV viremia and chronic liver disease. SETTING: University and city hospitals.
      PARTICIPANTS: Spouses (52 men and 102 women; mean age, 56 +/- 11 years) of 154
      patients with HCV viremia (102 men and 52 women; mean age, 58 +/- 10 years), of
      whom 66 had chronic hepatitis, 49 had liver cirrhosis, and 39 had primary
      hepatocellular carcinoma. METHODS: Tests for HCV-associated antibodies were done
      using a second-generation enzyme immunoassay and immunoassays with synthetic
      oligopeptides deduced from the HCV core gene. Hepatitis C virus RNA was detected
      by polymerase chain reaction with primers deduced from the 5'-noncoding region
      and HCV genotypes by reaction with type-specific primers deduced from the HCV
      core gene. RESULTS: Hepatitis C virus-associated antibodies were detected in 42
      (27%) spouses, of whom 25 were also positive for HCV RNA. Of 112 (73%) spouses
      without detectable antibodies, 2 had chronic liver disease. The development of
      markers of HCV infection in spouses increased with the duration of marriage,
      ranging from 1 to 60 years (30 +/- 11 years). CONCLUSIONS: Spouses of patients
      with HCV viremia and chronic liver disease have an increased risk for acquiring
      HCV, which is proportional to the duration of marriage. They should be followed
      routinely for markers of HCV infection and liver disease.

PMID- 8147550
TI  - Noninvasive positive pressure ventilation to treat respiratory failure.
AB  - PURPOSE: To review the clinical use of noninvasive positive pressure ventilation,
      including its efficacy with acute and chronic forms of respiratory failure, its
      mechanism of action, and its implementation. DATA SOURCES: Studies were
      identified through a MEDLINE search using the key words respiratory failure and
      mechanical ventilation and through a manual review of reference lists of
      published articles. STUDY SELECTION: All original studies relating to the use of
      noninvasive positive pressure ventilation in respiratory failure were included.
      Because of the paucity of controlled trials, cohort studies were not excluded.
      DATA EXTRACTION: Study design, numbers and diagnoses of patients, ventilator
      modes, and success and complication rates were extracted and compiled. RESULTS:
      For acute respiratory failure, studies report improved gas exchange and avoidance
      of intubation in 60% to 80% of patients with chronic obstructive pulmonary
      disease, restrictive thoracic disease, congestive heart failure, pneumonia, or
      postoperative extubation failure. However, the patients were highly selected, and
      relatively few studies have been published, only one of which was a randomized
      controlled trial. For chronic respiratory failure due to restrictive thoracic
      disease, all studies report improved gas exchange and symptoms of hypoventilation
      after prolonged nocturnal use, although no study was controlled. Some cohort
      studies of patients with severe chronic obstructive pulmonary disease yielded
      favorable results, but longer-term, randomized, controlled studies showed
      minimal, if any, benefit. CONCLUSION: Noninvasive positive pressure ventilation
      is effective in the treatment of chronic respiratory failure due to restrictive
      thoracic diseases. The routine use of such treatment for chronic respiratory
      failure due to chronic obstructive pulmonary disease and for acute respiratory
      failure needs to be studied in randomized controlled trials in better-defined
      patient subsets.

PMID- 8147551
TI  - Selected treatment strategies for septic shock based on proposed mechanisms of
      pathogenesis.
AB  - PURPOSE: To review selected new therapies for septic shock designed to inhibit
      bacterial toxins or endogenous mediators of inflammation. DATA SOURCES:
      Scientific journals, scientific meeting proceedings, and Food and Drug
      Administration advisory committee proceedings. STUDY SELECTION AND EXTRACTION:
      Preclinical and clinical data from trials using core-directed antiendotoxin
      antibodies and anticytokine therapies for sepsis and studies in animal models of
      sepsis from our laboratory. RESULTS OF DATA SYNTHESIS: Ten clinical trials using
      core-directed antiendotoxin antibodies produced inconsistent results and did not
      conclusively establish the safety or benefit of this approach. Both anti
      interleukin-1 and anti-tumor necrosis factor (TNF) therapies have been beneficial
      in some animal models of sepsis but did not clearly improve survival in initial
      human trials, and one anti-TNF therapy actually produced harm. Neutrophils,
      another target for therapeutic intervention, protect the host from infection but
      may also contribute to the development of tissue injury during sepsis. In a
      canine model of septic shock, granulocyte colony-stimulating factor increased the
      number of circulating neutrophils and improved survival, but an anti-integrin
      (CD11/18) antibody that inhibits neutrophil function worsened outcome. Nitric
      oxide, a vasodilator produced by the host, causes hypotension during septic shock
      but may also protect the endothelium and maintain organ blood flow. In dogs
      challenged with endotoxin, the inhibition of nitric oxide production decreased
      cardiac index and did not improve survival. CONCLUSIONS: No new therapy for
      sepsis has shown clinical efficacy. Perhaps more accurate clinical and laboratory
      predictors are needed to identify patients who may benefit from a given treatment
      strategy. On the other hand, the therapeutic premises may be flawed. Targeting a
      single microbial toxin such as endotoxin may not represent a viable strategy for
      treating a complex inflammatory response to diverse gram-negative bacteria.
      Similarly, the strategy of inhibiting the host inflammatory response may not be
      beneficial because immune cells and cytokines play both pathogenic and protective
      roles. Finally, our scientific knowledge of the complex timing of mediator
      release and balance during sepsis may be insufficient to develop successful
      therapeutic interventions for this syndrome.

PMID- 8147552
TI  - Characteristics of potential plaintiffs in malpractice litigation.
AB  - OBJECTIVE: To characterize patients calling plaintiff attorneys' offices and
      claiming to have suffered injury caused by medical negligence. DESIGN: Telephone
      interviews with an inception cohort of callers to law firms with malpractice
      complaints before the callers talk to attorneys. SETTING: Six law offices in five
      states. PARTICIPANTS: 502 of 730 callers over 10 randomly selected days in 1991.
      MEASUREMENTS: Demographics of potential plaintiffs, types of health care
      providers named by callers, factors prompting calls, economic and noneconomic
      motivations for claims, and disposition of claims. RESULTS: An average of 12
      calls per office per day were received by law firms concerning malpractice
      complaints. Many factors affected patients' decisions to call: poor relationships
      with providers before an injury (53%); television advertising by law firms (73%);
      explicit recommendations by health care providers to seek legal counsel (27%);
      impressions of not being kept informed or appropriately referred by providers;
      and financial concerns (for example, 36% with earned income and outstanding
      medical bills had bills equaling or exceeding 50% of their annual income, 33%
      were unemployed, and 31% lacked health insurance). One in 30 calls led to the
      filing of a lawsuit. CONCLUSIONS: Calls to plaintiff law firms by patients are
      common, are motivated by diverse factors, represent dissatisfaction with modern
      health care, and infrequently lead to lawsuits.

PMID- 8147553
TI  - "Clinical Judgment" revisited: the distraction of quantitative models.
AB  - More than 25 years ago, in a book called Clinical Judgment, each act of patient
      care was described as having an experimental structure. The "experiments" needed
      substantial scientific improvement, however, in quality of basic data, taxonomic
      classification of phenomena, and specifications of clinical reasoning. During the
      past 2 decades, these improvements have not occurred as extensively as expected
      because many investigators working in clinical forms of clinical research have
      not addressed these basic scientific challenges in data, taxonomy, and reasoning.
      Instead, the investigators have applied quantitative "models," derived from non
      clinical domains, that focus on hard data, randomized trials, Bayes theorem,
      quantitative decision analysis, and psychometric strategies for clinimetric
      measurement. Consequently, the main challenges of clinical judgment still remain
      generally available for basic scientific research by investigative clinicians.

PMID- 8147554
TI  - It's a boy!

PMID- 8147555
TI  - Spousal transmission of the hepatitis C virus?

PMID- 8147556
TI  - Predisposition to cytomegalovirus infection of the gastrointestinal tract.

PMID- 8147557
TI  - Predisposition to cytomegalovirus infection of the gastrointestinal tract.

PMID- 8147558
TI  - Effects of lovastatin and pravastatin on coronary artery disease.

PMID- 8147559
TI  - Distinguishing central nervous system lymphoma from Toxoplasma encephalitis.

PMID- 8147560
TI  - Probable hantavirus pulmonary syndrome that occurred in New Mexico in 1975.

PMID- 8147562
TI  - Pharmaceutical desktop references.

PMID- 8147561
TI  - 5-Fluorouracil dermatitis prophylaxis with a nicotine patch.

PMID- 8147563
TI  - Pharmaceutical desktop references.

PMID- 8147565
TI  - An analysis of treatment options and outcome in patients with Parkinson's disease
      and severe dyskinesias.
AB  - Forty-one patients with Parkinson's disease and severe dyskinesias were analyzed
      retrospectively to determine if some general principles would emerge to aid
      physicians handling this complication of treatment. Dyskinesia type (high dopa
      chorea [HDC], low dopa chorea [LDC], high dopa dystonia [HDD], and low dopa
      dystonia [LDD]) predicted response to treatment and whether or not levodopa dose
      reduction would benefit dyskinesias without producing unacceptable "offs." High
      dopa chorea improved best but at the expense of increased "off" time, followed by
      LDD, HDD, and LDC. Levodopa reduction was an acceptable strategy in ameliorating
      HDC and LDD only. Adjunctive therapy benefited all dyskinesia types, although the
      majority of patients (12/17) helped by selegiline had LDD or LDC. Generally, low
      doses of dopamine agonists were helpful (bromocriptine < 20 mg/day; pergolide < 2
      mg/day). When adding adjunctive therapy (except for selegiline or controlled
      release carbidopa/levodopa), concomitant reduction in daily dose of levodopa was
      not an effective strategy to decrease dyskinesias. Serial trials of multiple drug
      regimens are useful in these patients.

PMID- 8147564
TI  - Thrombosis and coagulation abnormalities associated with cancer.
AB  - Abnormalities of hemostasis and malignancy have been recognized since the 19th
      century. Thrombosis and hypercoagulability are reported in as many as 60 percent
      of patients with malignancies. Decreased levels of protein coagulation factors,
      circulating anticoagulants and platelet numbers, and function changes are
      reported. The purpose of this work is to report a case of portal thrombosis in a
      patient with a myeloproliferative disorder and to review protein coagulation and
      platelet abnormalities associated with malignancies. The clinical laboratory
      assessment of these abnormalities is reviewed. The patient was a 59-year-old
      woman who was referred to the Vanderbilt University Medical Center with a
      diagnosis of septic portal vein thrombosis. After evaluation, it turned out that
      she had a myeloproliferative disorder and portal vein thrombosis secondary to
      that. Hypercoagulative states have been reported with a variety of carcinomas and
      other neoplasms. They may or may not be associated with acquired or genetic
      deficiencies of antithrombin III, protein C and/or S. Factors I, V, VIII:C, IX,
      and XI have all been reported as being elevated and implicated in
      hypercoagulability in patients with neoplasms. Increased platelet turnover and
      decreased survival have been noted in patients with disseminated tumors.
      Thromboses with lysis of the thrombus may be monitored by increased levels of
      fibrin degradation products, D-dimer, fibrinopeptides A and B, and platelet
      factor IV among others. There are frequently decreases in coagulation inhibitors
      including antithrombin III, protein C and protein S. These changes lead to a
      state of low-grade disseminated intravascular coagulopathy where thrombus
      formation is a more frequent occurrence than is hemorrhage.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8147566
TI  - Long-term oral administration of aluminum in mice. Aluminum distribution in
      tissues and effects on calcium metabolism.
AB  - Six months of oral administration of aluminum lactate provokes an important
      accumulation of aluminum in various tissues of mice. The accumulation magnitude
      order is spleen > kidney > brain > liver > blood. No systemic toxic effects
      (weight loss or neurolytic effects) were observed. Values of calcium content and
      45Ca-uptake by the different tissues showed no modifications of calcium
      metabolism. The lack of calcium homeostasis modification caused by a probable
      aluminum insolubilization, and the incidence of other individual factors on
      individual deviations from group behavior is discussed.

PMID- 8147567
TI  - Chemical pathology of homocysteine. II. Carcinogenesis and homocysteine
      thiolactone metabolism.
AB  - Abnormalities of methionine metabolism in malignancy include carcinogenicity of
      methionine deficiency, methionine auxotrophy of cultured malignant cells,
      deficient methylation of DNA, and aerobic glycolysis that is reversed by
      methionine. Cells from children with homocystinuria form an aggregated sulfated
      extracellular matrix and grow in a pattern similar to cultured malignant cells.
      Normal cells metabolize homocysteine thiolactone to sulfate, but malignant cells
      accumulate homocysteine thiolactone, which thiolates proteins and other cellular
      macromolecules. Thioretinamide, the amide of retinoic acid homocysteine
      thiolactone, and its cobalamin complex, thioretinaco, are antineoplastic and
      chemopreventive against carcinogenesis. Deficiency of these compounds in
      malignant cells is believed to increase conversion of methionine to homocysteine
      thiolactone and thioco, its cobalamin complex. These compounds are believed to
      participate in oxidative phosphorylation by formation of thioretinaco ozonide
      disulfonium complexes that are the active sites of adenosine triphosphate (ATP)
      binding in mitochondrial membranes. Hypothetical deficiency of thioretinaco may
      explain important metabolic abnormalities of malignant cells.

PMID- 8147568
TI  - The role of flow cytometry in the diagnosis of lymphoma: a critical analysis.
AB  - Flow cytometry, now used routinely to aid in the classification of leukemias, is
      increasingly being evaluated as a rapid technique for determination of surface
      antigens on the cells teased from lymph nodes and other masses with suspected
      lymphoma. The present study reviews biopsy specimens from patients examined
      during a two year period which were sent for flow cytometry with a diagnosis of
      suspected lymphoma. Sixteen of 25 samples (64 percent) produced cell suspensions
      of sufficient quantity and quality to be diagnostically helpful. Results showed
      that in 9/16 (56 percent) the diagnosis of lymphoma or cancer could be suspected
      by flow cytometry alone, while 4/16 were consistent with the final tissue
      diagnosis of normal or reactive hyperplasia. Three samples that came from
      patients who had morphologic evidence of malignant disease on biopsy (two
      Hodgkin's disease and one large cell lymphoma) had flow cytometry results that
      were interpreted as normal. Flow cytometry is rapid and appears to be virtually
      diagnostic of non-Hodgkin's lymphoma when a majority of cells are B cells with an
      abnormal kappa/lambda ratio (> 4.0 or < 0.25). Nonhematologic malignancy can be
      suspected if less than 75 percent of the cells show CD45 (common leukocyte
      antigen). Hodgkin's disease cannot be detected by flow cytometry as it is
      currently used, and as many as 15 percent (1/6 in this study) of lymphomas may
      show normal results. It is extremely helpful when the biopsy sample actually
      contains the cells of interest in large proportion. Loss of architectural
      relationships in the course of processing specimens for flow cytometry is a major
      disadvantage when small foci of lymphoma or tumor cells exist together with large
      amounts of stroma or normal lymphocytes.

PMID- 8147569
TI  - Therapeutic monitoring of cyclosporine.
AB  - Therapeutic monitoring of immunosuppressive therapy with cyclosporine is a
      critical requirement because of intra- and interpatient variability of drug
      absorption, narrow therapeutic window and drug induced nephrotoxicity. The most
      widely used procedure involves measuring trough concentrations of cyclosporine
      (CsA) parent drug in whole blood using a specific monoclonal immunoassay. Trough
      concentrations generally correlate with adverse clinical events, e.g., episodes
      of rejection and nephrotoxicity. However, they do not correlate consistently with
      chronic events to allow prediction of adverse outcome. There is now increasing
      interest in using CsA pharmacokinetic profiling as a means of monitoring. This
      approach appears to offer a more valid index of drug exposure and hence a better
      prediction of clinical outcome. Nevertheless, multiple blood sample requirement
      and the complexity of pharmacokinetic profiling impose practical concern. The
      overall merit of either approach awaits further studies comparing clinical
      efficacy, technical requirements, and economic issues.

PMID- 8147570
TI  - Lipid peroxidation in platelet concentrates: effects of leukocyte removal by
      filtration.
AB  - Increased lipid peroxidation (LP) occurs in the presence of various transition,
      metal ions, including copper and iron, as well as various heme moieties. In
      addition, irradiation significantly increases LP. The degree of LP, as determined
      by the liquid chromatographic measurement of plasma malondialdehyde (MDA), can be
      significantly reduced by the addition of various metal chelating agents and other
      antioxidants to both stored red blood cells and platelet concentrates. They are
      also effective in reducing the degree of LP following irradiation. In the current
      study, leukocytes were effectively removed by filtration from platelet
      concentrates prepared by standard methods (mean +/- SD before filtration, 460 +/-
      286 per microL vs 0.3 +/- 0.2 per microL after filtration). The removal of the
      white blood cells significantly reduced the plasma MDA levels in the leukocyte
      free platelet concentrates compared with concentrates containing leukocytes after
      storage for 4, 7, and 11 days (P < 0.001; P < 0.02; P < 0.05, respectively). In
      addition, plasma potassium levels were also significantly reduced in the
      leukocyte-free platelet concentrates (P < 0.001). Our results suggest that the
      early removal of leukocytes from platelet concentrates may be helpful in
      prolonging platelet viability and longevity.

PMID- 8147571
TI  - The effect of macrophage conditioned media on Leydig cell function.
AB  - Primary gonadal failure frequently occurs in male patients with serious illness.
      This has suggested that activation of the immune system may affect the endocrine
      function of the testis. Most previous studies have evaluated the effects of
      individual cytokines on testosterone (T) production but with conflicting results.
      The present study was performed to compare the effects on Leydig cell function of
      a mixture of cytokines found in macrophage conditioned media (MCM), with that of
      individual recombinant cytokines. The MCM was found to contain an acid stable,
      heat labile, 16.5 kD factor(s) which significantly decreased the production of
      testosterone (T), dihydrotestosterone (dHT), adenosine 3':5'-cyclic monophosphate
      (cAMP), and guanosine 3':5'-cyclic monophosphate (cGMP). The MCM had no effect on
      the specific binding of human chorionic gonadotropin (hCG) but decreased the
      activity of 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) (a regulated Leydig
      cell enzyme). Neither tumor necrosis factor alpha (TNF alpha) interleukin 1 alpha
      (IL1 alpha), interleukin 1 beta (IL1 beta), interleukin 2 (IL2), interleukin 6
      (IL6), or human interferon alpha,beta (IFN alpha,beta) had a similar effect.
      These results show that the cytokines or other factor(s) contained in MCM are
      potent regulators of T production, which could be important in understanding the
      low serum T levels associated with serious illness.

PMID- 8147572
TI  - Is real-time quality assessment of health care an achievable goal?
AB  - Hospital-wide and real-time clinical outcome evaluation systems promote optimal
      quality of care with contained costs. These measurements of achieved health care
      benefits are critical for the ongoing process of national health care
      improvement. A practical hospital-wide quality improvement method, developed in
      the Veterans Administration Medical Center-Salt Lake City (VAMC-SLC), that
      evaluates positive, neutral, and negative outcome in relation to the mutual
      interactions between the health care provider, equipment, methodology, and
      patient is discussed. Real time or retrospective application of this analytical
      template to high risk procedures generates patient, practitioner, equipment, and
      methodology specific data to coordinate hospital-wide continuous quality
      improvement and cost containment efforts. It also allows system-wide comparative
      assessments of progress in the achievement of benefits within the national health
      care plan.

PMID- 8147573
TI  - Monitoring the heights of prepubertal children.
AB  - If the height of a prepubertal child is measured at one time and again a year
      later, any decision about the child's growth should be based on the distributions
      of the later height and height velocity conditional on the value of the initial
      height. The standard charts for height and height velocity derived by Tanner,
      Whitehouse and Takaishi (TWT) (1966) can be used in this context provided a
      correction is subsequently made, either by calculation or by reference to a
      suitable table. Moreover, the data provided by TWT, on which the charts are
      based, can be used to show that, over a certain age-range, the correlation
      between successive 12-month heights of a child is greater than 0.9 and approaches
      1 with increasing age. On the other hand, the correlation between the height at
      any age and the velocity over the ensuing 12 months is low, while the correlation
      between two successive 12-month velocities is so low as to make it reasonable to
      treat them as independent. One phenomenon that has been much observed is that a
      child who grows along the third centile for height seems to grow along the 25th
      30th centile for velocity. This effect follows when a conditional velocity is
      plotted onto a chart giving the distribution of an unconditional velocity. There
      is, moreover, a slight regression back to the population mean from any age to the
      next; this has little effect on the mean height but a noticeable effect on the
      mean velocity.

PMID- 8147574
TI  - Marital exogamy in the Aland Islands, Finland, 1750-1949.
AB  - Marriage records from 1750 through 1949 were used to examine effects of
      population size, geographic distance, and temporal change on rates of marital
      exogamy in the Aland Islands, Finland. Exogamy rates for individuals (not
      couples) were computed for 15 Aland parishes in each of four 50-year time
      periods, giving a total of 60 observations. These rates were analysed with
      respect to population size using a quadratic regression model. Regression
      analyses were also used to examine the relationship of marital exogamy with two
      measures of geographic distance--average distance to all other parishes and
      nearest-neighbour distance. Analysis of variance was used to examine temporal
      trends. Multiple regression analyses were used to examine all of these factors
      simultaneously. Marital exogamy is highest in smaller and larger populations, and
      less in medium-sized populations. Higher exogamy rates in small populations are
      related to the lack of available mates in small groups. Higher exogamy rates in
      larger populations may reflect economic attraction of larger groups. Exogamy
      rates are lower in the more geographically isolated parishes. From 1750 through
      1899 there is little change in exogamy rates, whereas exogamy rates double after
      1900. This temporal change reflects changes in transportation technology and
      other cultural factors promoting increased migration. The multiple regression
      model shows population size, geographic distance, and temporal change are all
      significant correlates of exogamy, collectively explaining a large percentage of
      variation in rates (R2 = 0.79).

PMID- 8147575
TI  - The measurement of body fat distribution using somatotype photographs and
      computer-assisted imaging techniques.
AB  - A computer-assisted image analysis technique has been devised which allows the
      measurement of body fat distribution from archived somatotype photographs. This
      report describes the technique, which enables useful measurements to be extracted
      from somatotype photographs which were taken over 50 years ago. This paper
      describes the process of digitization of photographs, the measurement of body
      diameters using computer-assisted edge detection, the quantitative analysis of
      measurement error in this procedure, and validation techniques employed.

PMID- 8147576
TI  - The distribution of body fat from childhood to adulthood in a longitudinal study
      population.
AB  - Body fat distribution, its continuity from childhood (4-6 years) to 30 years of
      age, and its link to that of parents is described in a longitudinal study
      population. A computer-assisted image analysis technique was used to measure body
      fat distribution (as measured by waist and hip diameters) from somatotype
      photographs. Pearson correlation coefficients were used to assess the association
      between the waist/hip diameter ratio (WHDR) and the body mass index (BMI) at all
      ages and between the WHDR of parents and offspring. Both Pearson correlation
      coefficients and the Foulkes-Davis tracking index were used to assess tracking of
      the WHDR from childhood to age 30 years. Stepwise regression analyses were
      performed to determine the predictability of the WHDR at age 30 years from WHDRs
      in childhood and adolescence. Among both sexes the WHDR decreased and BMIs
      increased with age from childhood to 18 years, then both increased from age 18 to
      30 years. The correlation between the WHDR and BMI was significant only at 30
      years for males (r = 0.37; p < 0.05) and during all stages of adolescence in
      females (p < 0.05). Age-to-age correlations were high for both sexes (p <
      0.0001), and remained significant over a span of up to 25 years. Using the
      Foulkes-Davis tracking index, tracking from the year of peak height velocity to
      30 years (a span of approximately 20 years) was strong for both sexes. Parent and
      child WHDRs were correlated and differed by sex. Father-son correlations were not
      significant in childhood, but reached significance in early adolescence (2 years
      before the year of peak velocity) and remained significant to 30 years (p <
      0.05). Mother-daughter correlations were significant at all ages (p < 0.05). The
      level of the WHDR at the peak of the pubertal growth spurt (year of peak height
      velocity) predicted up to 58% of the variance in males and 51% of the variance in
      females of the WHDR at 30 years. We conclude that the adult WHDR (a proxy for the
      waist/hip ratio) becomes evident by the year of the pubertal growth spurt in
      height.

PMID- 8147577
TI  - The growth of XXX females: population-based studies.
AB  - Longitudinal measurements of height, sitting height and leg length are compared
      between 11 XXX girls identified by cytogenetic screening, and 16 chromosomally
      normal controls from the same population using a nonparametric method. While
      height velocity did not differ between the two groups either during the pubertal
      or the mid-childhood spurts, leg length velocity was significantly increased
      during the mid-childhood spurt, between 4 and 9 years of age. A further
      contribution to the increased leg length came from the slower decline in leg
      length velocity at the end of the pubertal spurt. The possible mechanisms
      involved in these changes are discussed.

PMID- 8147578
TI  - The Cayapa Indians of Ecuador: a population study of seven protein genetic
      polymorphisms.
AB  - The Cayapa Indians are a population of 3600 individuals living in Ecuador, along
      the Cayapas River and its tributaries. They are thought to have migrated from the
      Andes, north of Quito, and settled in the Cayapas area five centuries ago as a
      consequence of Inca expansion and of the Spanish conquest. In order to study the
      genetic structure of the Cayapa and their relationships with other native
      American peoples, and to enquire on the possibility of admixture from nearby
      Black communities, we have investigated a sample of 139 individuals for seven
      plasma genetic markers (F13A, F13B, ORM1, AHSG, C6, C7 and APOC2) by isoelectric
      focusing and immunoblotting. The following gene frequencies have been found:
      F13A*1 = 0.824, F13A*2 = 0.176; F13B*1 = 0.126, F13B*3 = 0.874; ORM1*1 = 0.554,
      ORM1*2 = 0.446; AHSG*1 = 0.275, AHSG*2 = 0.725; C6*A = 0.131, C6*B = 0.814,
      C6*A21 = 0.055; C7*1 = 1.000; APOC2*1 = 1.000. The findings confirm, whenever the
      comparison was possible, quite a good resemblance of the Cayapa with other Native
      American populations.

PMID- 8147579
TI  - Relative sitting height and the interpretation of the body mass index.
AB  - The body mass index (BMI) is being used widely as an index of overweight and
      undernutrition. The effects of variations of shape as evinced by relative sitting
      height (sitting height/stature, SH/S) on BMI were determined using mean data from
      95 samples of men and 63 samples of women of non-European origin, representing
      18,000 individuals. The linear regression coefficients of BMI on SH/S (b +/-
      standard error) were 0.78 +/- 0.16 (t = 4.8) in men and 1.19 +/- 0.22 (t = 5.3)
      in women. Correlations coefficients were 0.45 and 0.56, respectively. These
      regression coefficients compare with a predicted change of 0.9 kg/m2 per 0.01
      difference in SH/S using a modelling approach. The wide variation within and
      between populations precludes a simple adjustment for SH/S, and in the
      interpretation of BMI additional anthropometric measurements may be necessary.

PMID- 8147580
TI  - Normalizing transformations for growth standards.

PMID- 8147581
TI  - Cationic liposomes mediated delivery of antisense oligonucleotides targeted to
      HPV 16 E7 mRNA in CaSki cells.
AB  - The "high risk" types 16 and 18 of human papillomavirus (HPV) are involved in the
      etiology of genital squamous cell carcinoma. The early genes 6 and 7 (E6-E7) of
      these viruses code for the major transforming proteins, capable of inducing cell
      transformation alone or acting synergistically with other oncogenes. Antisense
      oligonucleotides, recently applied to inhibit the functions of a number of
      cellular and viral proteins, might provide the basis for a new therapeutic
      strategy against HPV-induced malignancies. We studied the proliferation of CaSki
      cells by the MTT assay after their exposure to HPV 16 E7 mRNA antisense
      oligonucleotides with and without cationic liposomes (containing
      dimethyldioctadecylammonium bromide DDAB, and dioleylphosphatidylethanolamine,
      DOPE). Unmodified oligonucleotides (either 12- or 23-mers) did not have any
      effect on either CaSki cell proliferation or morphology when compared with the
      untreated cells. The cellular uptake of oligonucleotides was significantly
      enhanced by the cationic liposomes as assessed by confocal laser scanning
      microscopy (CLSM). The cationic liposomes were toxic to the cells as demonstrated
      by the reduced cell number and altered cell morphology. Only a slight reduction
      of the cell proliferation was seen when antisense 12-mer was protected from its
      3'- and 5'-ends with thiolate and FITC, respectively. Both the 12- and the 23
      mers with the cationic liposomes inhibited cell proliferation, the inhibitory
      effect being longer with the 23-mer. Overall, the MTT assay was less sensitive
      than light microscopy to reveal the toxic effects on CaSki cells. The results
      suggest that antisense oligonucleotides targeted to HPV 16 E7 mRNA can be
      introduced into CaSki cells with cationic liposomes.

PMID- 8147582
TI  - Echinhibin-1--an inhibitor of Sendai virus isolated from the venom of the snake
      Echis coloratus.
AB  - The snake venom of Echis coloratus was found to abolish the hemagglutinating
      activity, hemolytic activity and in vivo infectivity of Sendai virus. The active
      factor (Echinhibin-1) was purified by gel filtration on Sephadex G-50, followed
      by chromatography on DEAE-Sepharose and CM-Sepharose. Echinhibin-1 is a protease
      with a molecular weight of about 25 kDa, an isoelectric point of 7 and is stained
      by PAS, indicating that it is a glycoprotein. It showed a strong azocollase
      activity that was stable up to 68 degrees C and at pH values of 4.5-10.5. Ten
      micrograms/ml were sufficient to abolish the hemolytic effect of the virus on
      human erythrocytes when incubation was at 37 degrees C for 2 h, while 20
      micrograms/ml abolished the hemagglutinating activity. Addition of Echinhibin-1
      after the adsorption of Sendai virions onto washed erythrocytes at 4 degrees C
      did not inhibit the subsequently hemolytic activity at 37 degrees C, indicating
      that Echinhibin-1 interferes with virus adsorption to the cells. Of various
      protease inhibitors, only Na2 EDTA and o-phenanthroline inhibited the antiviral
      activity of the purified factor, indicating that it is a metalloproteinase. In
      vivo, mice inoculated intranasally with the virus pretreated with Echinhibin-1
      developed well and gained weight, whereas untreated virus-infected mice lost
      weight and died within 1 week. Intravenous administrations of the purified factor
      up to 80 micrograms/mouse produced no signs of toxicity and subcutaneous
      injections caused no hemorrhagic activity, while the whole venom is very
      hemorrhagic with an LD50 of 250 micrograms/kg for mice.

PMID- 8147583
TI  - Efficacy of A-73209, a potent orally active agent against VZV and HSV infections.
AB  - A-73209 is a novel oxetanocin derivative with potent in vitro and in vivo
      activity against VZV, HSV-1, and HSV-2. A-73209 was two logs more potent than
      acyclovir against five thymidine kinase positive (TK+) strains of VZV in vitro
      (mean EC50 0.01 vs. 1.22 micrograms/ml). The activity of A-73209 was one log more
      potent than acyclovir against TK+ HSV-1 strains in vitro (EC50 = 0.03 vs. 0.32
      micrograms/ml). A-73209 yielded a mean EC50 of 2.2 micrograms/ml compared to a
      mean EC50 of 0.37 micrograms/ml for acyclovir against a panel of TK+ HSV-2
      strains in vitro. The in vitro activity of A-73209 against thymidine kinase
      negative or deficient strains of VZV, HSV-1 and HSV-2 was much lower than for the
      corresponding TK+ strains. A-73209 produced efficacy superior to acyclovir
      against lethal systemic or intracerebral HSV-1 infections in mice. The greater
      efficacy of A-73209 relative to acyclovir was especially apparent with oral
      dosing. Against HSV-2 infections in mice, the efficacy of A-73209 ranged from
      equal to 1.7 times less active relative to acyclovir with oral dosing. A-73209
      was orally bioavailable in mice, with maximal serum concentrations well in excess
      of in vitro inhibitory concentrations. A-73209 appears to be a potent and
      selective agent against varicella-zoster virus and herpes simplex virus
      infections.

PMID- 8147584
TI  - True reform will ensure a strong nursing presence in the OR.

PMID- 8147585
TI  - Watch out for 'friendly fire' from our medical allies!

PMID- 8147586
TI  - Specialty surgical teams.

PMID- 8147587
TI  - Malignant hyperthermia. Are you prepared?

PMID- 8147588
TI  - Malignant hyperthermia. Epidemiology, pathophysiology, treatment.

PMID- 8147589
TI  - External ear reconstruction. Use of a pivoting helix, porous polyethylene
      implant.
AB  - We have used the porous polyethylene, pivoting helix framework for ear
      reconstruction at RLAMC since 1989 with no major complications. Postoperatively,
      patients have an external ear that resembles a normal ear and is sturdy enough to
      support eye wear. The aesthetic results have been well received by the patients
      and their families (Fig 8). Most children are reluctant to undergo surgery;
      however, those patients with ear deformities often are eager for external ear
      reconstruction surgery, and the majority of our pediatric patients have been
      pleased with the postoperative results (Fig 9). The success of this procedure
      depends on a number of factors, including proper patient selection, suitable
      selection of materials for the reconstruction, the technical skills of the
      surgeon, and the surgical team's attention to detail in the intraoperative
      period. The perioperative nurse, functioning as the patient advocate, plays an
      integral role in the success or failure of this procedure.

PMID- 8147590
TI  - A collaborative ambulatory preoperative evaluation model. Implementation,
      implications, evaluation.

PMID- 8147591
TI  - Traffic control. A study of traffic control in total joint replacement
      procedures.

PMID- 8147592
TI  - Nurses' knowledge, attitudes about HIV, AIDS. A replication study.
AB  - The AIDS epidemic is now in its second decade and shows no sign of relenting.
      Unfortunately, however, the AORN study shows that perioperative nurses' knowledge
      regarding HIV and AIDS is not adequate to enable them to provide patient care
      while maintaining safe practices. Focused educational programs should be made
      available to perioperative nurses to help them apply universal precautions and
      OSHA standards to everyday practice. Perioperative nurses must become
      knowledgeable about the disease and sensitive to the needs of patients who have
      this illness. All nurses have a special obligation to care for all patients;
      education and management strategies that enable exploration of values, fears, and
      prejudices will help nurses understand their own beliefs and those of other
      individuals. Recommendations from this study may be viewed as a starting point
      for this perioperative education.

PMID- 8147593
TI  - Developing laser competencies. A process to ensure safe practice.

PMID- 8147594
TI  - Periopardy. An innovative learning tool.

PMID- 8147595
TI  - Infection control. Quality assessment, improvement.

PMID- 8147596
TI  - All the right moves. A program to reduce back injuries in OR nurses.

PMID- 8147597
TI  - Product evaluation process. A systems approach to controlling health care costs.

PMID- 8147598
TI  - Proposed recommended practices. Endoscopic minimal access surgery. Association of
      Operating Room Nurses.

PMID- 8147599
TI  - Proposed recommended practices. Surgical tissue banking. Association of Operating
      Room Nurses.

PMID- 8147600
TI  - Supreme Court rules on landmark sexual harassment case.

PMID- 8147601
TI  - HIV patients have good surgery outcomes.

PMID- 8147602
TI  - Selecting one health care reform plan is not an easy choice.

PMID- 8147603
TI  - Autologous splenic transplantation.

PMID- 8147604
TI  - Autologous splenic transplantation for splenic trauma.
AB  - OBJECTIVE: The authors reviewed the experimental evidence, surgical technique,
      complications, and results of clinical trials evaluating the role of autologous
      splenic transplantation for splenic trauma. SUMMARY BACKGROUND DATA:
      Splenorrhaphy and nonoperative management of splenic injuries have now become
      routine aspects in the management of splenic trauma. Unfortunately, not all
      splenic injuries are readily amenable to conventional spleen-conserving
      approaches. Heterotopic splenic autotransplantation has been advocated for
      patients with severe grade IV and V injuries that would otherwise mandate
      splenectomy. For this subset of patients, splenic salvage by autotransplantation
      would theoretically preserve the critical role the spleen plays in the host's
      defense against infection. METHODS: The relevant literature relating to
      experimental or clinical aspects of splenic autotransplantation was identified
      and reviewed. Data are presented on the experimental evaluation of autogenous
      splenic transplantation, methods and complications of autotransplantation, choice
      of anatomic site and autograft size, and results of clinical trials in humans.
      RESULTS: The most commonly used technique of autotransplantation in humans
      involves implanting tissue homogenates or sections of splenic parenchyma into
      pouches created in the gastrocolic omentum. Most authors have observed evidence
      of splenic function with normalization of postsplenectomy thrombocytosis,
      immunoglobulin M levels, and peripheral blood smears. Some degree of immune
      function of transplanted grafts has been demonstrated with in vivo assays, but
      the full extent of immunoprotection provided by human splenic autotransplants is
      currently unknown. CONCLUSIONS: Multiple human and animal studies have
      established that splenic autotransplantation is a relatively safe and easily
      performed procedure that results in the return of some hematologic and
      immunologic parameters to baseline levels. Some aspects of reticuloendothelial
      function are also preserved. Whether this translates into a real reduction in the
      morbidity or mortality rates from overwhelming bacterial infection is unknown and
      requires further investigation.

PMID- 8147605
TI  - Current treatment modalities for hepatocellular carcinoma.
AB  - OBJECTIVE: This study evaluated the currently available treatment modalities for
      hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: One of the most common
      tumors worldwide, HCC has several known risk factors. Untreated HCC typically has
      a dismal prognosis. Early detection remains the key to successful treatment of
      this malignancy. Surgical resection has been the mainstay of treatment for HCC,
      but newer modalities have been recently introduced. METHODS: The authors
      evaluated the treatment modalities for HCC. RESULTS: Surgical resection affords 5
      year survival rates as high as 45% with more favorable subgroups having 1) small
      tumors, 2) well-differentiated tumors, 3) unifocal tumors, 4) lack of vascular
      invasion, 5) absence of cirrhosis, and 6) the fibrolamellar variant (FL-HCC).
      Resection has been limited primarily by low resectability rates and recurrent
      disease. Newer therapeutic modalities that appear the most promising are
      transarterial chemoembolization and percutaneous ethanol injection. Neither
      therapy has been evaluated in a prospective randomized manner. Combination
      chemotherapy and surgical intervention may provide the best results, but
      randomized controlled trials with long-term follow-up are needed. As single
      treatment modalities, radiation therapy, intravenous chemotherapy, intra-arterial
      chemotherapy, and immunotherapy play limited palliative roles. CONCLUSIONS:
      Surgical resection in the form of partial or total hepatectomy is the preferred
      treatment for HCC. The early detection of tumors by screening high-risk
      populations is crucial. Randomized trials of combinations of chemotherapy and
      surgical resection are needed to demonstrate their potential utility for
      treatment.

PMID- 8147606
TI  - Induction of anaerobic glucose metabolism during the development of acute
      pancreatitis.
AB  - OBJECTIVE: Studies were performed with the ex vivo perfused canine pancreas
      preparation to characterize acinar cell metabolism during the development of
      acute pancreatitis. SUMMARY BACKGROUND DATA: Acute pancreatitis can be initiated
      in the ex vivo perfused canine pancreas preparation by five different stimuli as
      follows: (1) the infusion of oleic acid (FFA), (2) partial obstruction of the
      pancreatic duct and secretin stimulation (POSS), (3) a 2-hour ischemic period
      before perfusion (ISCH 2), (4) a 1-hour ischemic period followed by acetaldehyde
      infusion (ISCH 1 + AA), and (5) supramaximal stimulation by cerulein (CER-HIGH).
      In each model, weight gain, edema formation, and hyperamylasemia occur,
      signifying the development of pancreatitis. Previously, the authors demonstrated
      that intracellular adenosine triphosphate (ATP) levels decline during the
      development of pancreatitis in the FFA model but not in the other four models.
      METHODS: The ex vivo perfused canine pancreas preparation was used to study five
      different stimuli that result in the initiation of acute pancreatitis, as
      manifested by weight gain, edema formation, and hyperamylasemia during a 4-hour
      perfusion period. Glucose metabolism (using 13C-labeled glucose) and
      intracellular pH and ATP levels were monitored by magnetic resonance
      spectroscopy. Oxygen consumption and pancreatic secretion were measured directly.
      RESULTS: In control preparations, a glucose signal appeared in the 13C-labeled
      spectra within 15 minutes, and a signal from glycogen appeared at the end of the
      4-hour perfusion. In the preparations with an ischemic period (ISCH 2 and ISCH 1
      + AA), a lactate signal appeared during the ischemia, disappeared during the
      early perfusion, and appeared again later during the perfusion as the physiologic
      injury response of pancreatitis developed. Similarly, in the POSS and CER-HIGH
      pancreatitis preparations, lactate accumulated in the pancreas during the
      perfusion period. In these four preparations, the intracellular pH did not differ
      significantly during the perfusion from that of the control preparations. Oxygen
      consumption was unchanged during the perfusion in the ISCH 2 and ISCH 1 + AA
      preparations and increased in the POSS and CER-HIGH preparations. In the FFA
      pancreatitis preparations, only a trace of glycogen was observed, and the
      metabolites of glucose were not detected. Intracellular pH and oxygen consumption
      both dropped significantly during the perfusion. CONCLUSIONS: In four of the five
      acute experimental pancreatitis models, anaerobic glucose metabolism was induced,
      despite continuous oxygen extraction by the pancreas. This induction of anaerobic
      glucose metabolism may be important in maintaining normal levels of intracellular
      ATP early after the induction of pancreatitis because the absence of anaerobic
      glucose metabolism in the FFA model was associated with a remarkable decrease in
      intracellular ATP levels and pH. The FFA model of pancreatitis is the most severe
      of the five models.

PMID- 8147608
TI  - Surgical treatment of 724 carcinomas of the gallbladder. Results of the French
      Surgical Association Survey.
AB  - OBJECTIVE: The objective of this study was to evaluate the benefit of an
      aggressive approach to gallbladder carcinoma on long-term survival. SUMMARY
      BACKGROUND DATA: Recent studies have shown that an aggressive surgical treatment
      of bile duct carcinoma can be associated with a surprising long-term survival.
      However, recent data on gallbladder carcinoma are not available. METHODS: Data
      were obtained from a questionnaire sent to 73 institutions in France, Europe, and
      overseas, and they were analyzed retrospectively. The review included an analysis
      of patient sex and age, associated hepatobiliary diseases, symptoms and signs,
      diagnostic tests, operative management, pathology reports, and survival. RESULTS:
      Seventy-eight per cent of the patients were women, and 22% were men (p < 0.001).
      Gallstones were present in 86% of the cases. Four per cent of the patients had
      Tis stage lesions, 11% had T1 to T2 stage lesions, and 85% had T3 to T4 stage
      lesions (p < 0.001). Pain was the most frequent symptom (77%). Twenty-three per
      cent of the patients underwent curative operations, and 77% had a palliative
      treatment (25% of the patients underwent exploratory laparotomy). Exploratory
      laparotomy was followed by the highest mortality rate (66%), and older patients
      (> 70 years) had a higher operative risk (p < 0.04). The overall median survival
      was 3 months, and long-term survival correlated with the cancer stage (Tis, > 60
      months; T1 to T2, > 22 months, and T3 to T4, 2 to 8 months). No differences were
      observed among the different surgical procedures adopted. CONCLUSIONS: No
      progress has been made in the last 10 years in the treatment of gallbladder
      malignancies.

PMID- 8147607
TI  - Carcinoma of the extrahepatic bile ducts. The University of California at San
      Francisco experience.
AB  - OBJECTIVE: The authors investigated the combined experience of a single
      institution in treating bile duct carcinoma during the modern era. SUMMARY
      BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with
      locoregional recurrence the rule, even after radical resection. Adjuvant efforts
      have included various radiation modalities, with limited success. Recently,
      charged-particle radiotherapy has also been used in these patients. METHODS: The
      authors performed a retrospective chart analysis of 129 patients with bile duct
      adenocarcinomas treated between 1977 and 1987 through the University of
      California at San Francisco, including 22 patients treated at Lawrence Berkeley
      Laboratory with the charged particles helium and neon. The minimum follow-up was
      5 years. Survival, outcome, and complication results were analyzed. RESULTS:
      Sixty-two patients were treated with surgery alone (S), 45 patients received
      conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with
      charged particles (S + CP). The median survival times were 6.5, 11, and 14
      months, respectively, for the entire group, and 16, 16, and 23 months in patients
      treated with curative intent. There was a survival difference in patients
      undergoing total resection compared with debulking (p = 0.05) and minor
      resections (p = 0.0001). Patients with microscopic residual disease had increased
      median survival times when they were treated with adjuvant irradiation, most
      markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109).
      Patients with gross residual disease had a less marked but still statistically
      significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP)
      after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was
      maximal surgical resection in these patients. Postoperative radiotherapy gave
      patients with positive microscopic margins a significant survival advantage and
      may be of value in selected patients with gross disease.

PMID- 8147609
TI  - Continuous assessment and improvement in quality of care. A model from the
      Department of Veterans Affairs Cardiac Surgery.
AB  - OBJECTIVE: The authors organized the Department of Veterans Affairs (VA)
      Continuous Improvement in Cardiac Surgery Study (CICSS) to provide risk-adjusted
      outcome data for the continuous assessment and improvement of quality of care for
      all patients undergoing cardiac surgery in the VA. BACKGROUND: The use of risk
      adjusted outcomes to monitor quality of health care has the potential advantage
      over consensus-derived standards of being free of preconceived biases about how
      health care should be provided. Monitoring outcomes of all health care episodes,
      as opposed to review of selected cases (e.g., adverse outcomes), has the
      advantages of greater statistical power, the opportunity to compare processes of
      care between good and bad outcomes, and the positive psychology of treating all
      providers equally. These two concepts, together with a pre-existing peer
      committee (the VA Cardiac Surgery Consultants Committee) to review, interpret,
      and act on the risk-adjusted outcome data, form the primary design considerations
      for CICSS. METHODS: Patient-level risk and outcome (operative mortality and
      morbidity) data are collected prospectively on each of the approximately 7000
      patients undergoing cardiac surgery in the VA each year. These outcomes, adjusted
      for patient risk using logistic regression, are provided every 6 months to each
      cardiac surgery program and to a national peer review committee for internal and
      external quality assessment and improvement. RESULTS: For the most recent 12
      month period with complete data collection, observed-to-expected (O/E) ratios
      ranged from 0.2 to 2.2, with eight centers falling outside of the 90% confidence
      limits for an O/E ratio equaling 1.0. The O/E ratio for all centers has fallen by
      14% over the 4.5-year period of this program (p = 0.06). CONCLUSIONS: A large
      scale, low-cost program of continuous quality improvement using risk-adjusted
      outcome is feasible. This program has been associated with a decrease in risk
      adjusted operative mortality.

PMID- 8147610
TI  - Impairment of pulmonary macrophage function with total parenteral nutrition.
AB  - OBJECTIVE: The effects of total parenteral nutrition (TPN) administration on
      pulmonary macrophage function and host response to gram-negative pulmonary
      infection were evaluated. SUMMARY BACKGROUND DATA: Administration of TPN resulted
      in increased infectious complications in traumatized and perioperative patients,
      but underlying mechanisms are unclear. METHODS: Twenty-six male Wistar rats
      underwent central vein cannulation and were randomized to isocaloric feeding of a
      regular chow diet (RD) plus saline infusion or TPN without chow diet for 7 days.
      Pulmonary alveolar macrophage (PAM phi) superoxide production, Candida albicans
      phagocytosis and killing, and tumor necrosis factor (TNF) production in response
      to endotoxin (LPS) were assessed. Mesenteric lymph nodes (MLN) were cultured. A
      second group of rats (n = 6/group) were inoculated intratracheally with a
      sublethal dose of 9 x 10(9) live Escherichia coli per animal, and the lungs were
      cultured quantitatively 72 hours later to assess bacterial clearance. Finally, 11
      RD-fed rats and 13 TPN-fed rats received intratracheal inoculation of 1.4 x
      10(10) live E. coli and were included in follow-up. RESULTS: Administration of
      TPN was associated with a significant increase in bacteria positive MLN compared
      with those in the RD group (p < 0.01). Pulmonary alveolar macrophage superoxide
      production, Candida albicans phagocytosis and killing, TNF production, and
      pulmonary clearance of bacteria were decreased significantly in TPN-fed rats
      compared with those fed a regular chow diet (p < 0.05). These pulmonary
      macrophage function changes were associated with a significantly higher mortality
      in TPN-fed rats compared with RD-fed rats after higher dose pulmonary E. coli
      inoculation. CONCLUSIONS: Defective host pulmonary antimicrobial immune responses
      during TPN are associated with intestinal bacterial translocation, and may
      explain increased infectious complications.

PMID- 8147611
TI  - A circulating shock protein depolarizes cells in hemorrhage and sepsis.
AB  - OBJECTIVE: A study to determine if both septic and hemorrhagic shock lead to the
      appearance of a substance that depolarizes cells in plasma was performed. SUMMARY
      BACKGROUND DATA: Transmembrane potential decreases in skeletal muscle,
      hepatocytes, and red blood cells early in the development of both hemorrhagic and
      septic shock. The associated movement of ions and water into cells leads to
      extracellular fluid loss and exacerbates shock. METHODS: Adult male Sprague
      Dawley rats with indwelling arterial and venous cannulae were bled 20 mL/kg or
      received intravenously 2 x 10(10) Escherichia coli suspended in 400 mL of 0.9%
      saline. Blood samples were taken after hemorrhage and induction of sepsis to
      determine the presence of a plasma factor that depolarized red blood cells.
      Control rats were not injected with E. coli or bled. Plasma from bled and septic
      rats was processed by sequential precipitation with ammonium sulfate and
      subjected to gel filtration. RESULTS: Depolarizing activity was highest 20
      minutes after hemorrhage and 60 minutes after E. coli injection, decreasing to
      control levels by 2 (hemorrhage) and 4 (sepsis) hours. Control rats showed no
      significant change in depolarizing activity. Tryptic and chymotryptic digestion
      eliminated the depolarizing activity, indicating that the active substance is, at
      least in part, a protein. Depolarizing activity from bled and septic processed
      plasma was confined essentially to the 70% ammonium sulfate fraction and the
      activity migrated with an apparent molecular mass of 200 kD after gel filtration.
      Separation of the complex by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) produced an identical pattern of bands in both bled
      and septic animals. CONCLUSIONS: A circulating plasma protein complex of high
      molecular weight causes cellular depolarization in both hemorrhage and sepsis and
      may be responsible for the associated increases in cell sodium and water seen in
      both hemorrhagic and septic shock.

PMID- 8147612
TI  - Recurrence at the bronchial stump after resection of lung cancer.
AB  - OBJECTIVE: Recurrence at the bronchial stump frequently is difficult to diagnose
      before the disease progresses. Patients with recurrence at the bronchial stump
      after surgical treatment were studied to clarify characteristics. SUMMARY
      BACKGROUND DATA: Reports on this type of recurrence are few. METHODS: Between
      January 1979 and December 1988, 625 primary lung cancers were resected. Fourteen
      patients (2.2%), in whom recurrence occurred at the bronchial stump, were studied
      pathologically and clinically. RESULTS: Eight tumors (57.1%) were squamous cell
      carcinomas, five (35.7%) were adenocarcinomas, and one (7.1%) was small cell
      carcinoma. Pathologically, six tumors (42.9%) were stage I, four (28.6%) were
      stage II, two (14.3%) were stage IIIA, and two (14.3%) were stage IV. Eight
      patients had bloody sputum at recurrence; two cases were asymptomatic. Submucosal
      tumors were observed bronchoscopically at recurrence in 11 patients. Considering
      lymphadenopathy on chest x-ray, the submucosal type recurrence may have been
      direct invasion from metastatic lymph nodes. The periods from the operation to
      the recurrence were 7 to 102 months (mean 28.8 months). In 8 of 14 patients,
      recurrence was observed within 24 months. All but one patient died within 24
      months of recurrence detection. CONCLUSIONS: Long survival could be expected only
      if there were no metastases in the mediastinal lymph nodes. If the tumors were
      detected earlier, it was possible to cure the tumors by intensive therapy, even
      in submucosal type recurrence. Regular bronchoscopic examination is needed to
      diagnose the recurrence at the bronchial stump as early as possible.

PMID- 8147613
TI  - Long-term results of subtotal esophagectomy with three-field lymphadenectomy for
      carcinoma of the thoracic esophagus.
AB  - OBJECTIVE: This study evaluated the impact of aggressive surgery on survival in
      patients with carcinoma of the thoracic esophagus. SUMMARY BACKGROUND DATA:
      Prognostic value of lymph-node status for patients with esophageal carcinoma was
      emphasized, although it is currently under debate whether extensive lymph node
      dissection improves survival. METHODS: Two hundred ninety-five patients with
      thoracic esophageal carcinoma were admitted to Kagoshima University Hospital from
      December 1982 to December 1990. Esophagectomy was performed on 244 (82.7%) of
      these patients; 106 of whom underwent three-field lymphadenectomy (bilateral
      cervical, mediastinal, and abdominal regions) were analyzed regarding lymph-node
      status, tumor recurrence, and the effect of prognostic factors on survival using
      Cox's proportional hazards model. RESULTS: Hospital mortality and morbidity were
      10.4% (11/106) and 65.1%, respectively. Seventy-eight patients (73.6%) had nodal
      involvement, including 49 patients with abdominal lymph-node metastases and 46
      patients with recurrent nerve-node metastases. Five-year survival rates were
      54.5% for 16 patients with a solitary nodal metastasis, 30.3% for stage III,
      17.4% for stage IV, and 7.2% for 28 patients with six or more metastatic nodes.
      The most frequent sites of recurrence were the upper mediastinal region and the
      lung--its incidence increased significantly as the number of positive nodes
      increased. The most unfavorable prognostic factors included regional or recurrent
      nerve-node metastasis and patient age of more than 71 years. CONCLUSIONS: Three
      field lymphadenectomy, including especially the removal of bilateral recurrent
      nerve nodes in the cervical region, is essential for improving the survival of
      patients with carcinoma of the upper two thirds of the thoracic esophagus.

PMID- 8147614
TI  - Laparoscopic ileostomy and colostomy.
AB  - OBJECTIVE: The technical features of laparoscopic ileostomy and colostomy are
      described. SUMMARY BACKGROUND DATA: A diverting ileostomy or colostomy can be
      performed with minimal trauma by laparoscopic techniques. This is distinct from
      the complex laparoscopic and laparoscopic-assisted resections of small and large
      bowel. To date the technical features of creating a diverting ileostomy or
      colostomy have not been emphasized sufficiently. METHODS: Standard laparoscopic
      techniques are used to create a pneumoperitoneum. After mobilization of the ileum
      or colon, a stoma is made on the abdominal wall. A trocar is introduced at the
      site where the stoma is located, thus reducing the technical problems associated
      with creating and maturing a stoma while the abdomen is insufflated. RESULTS:
      This approach obviates the need for a laparotomy while creating an ileostomy or
      colostomy. The technical features of creating a double-barrel ostomy, an end
      ostomy with a stapled distal limb, and a loop ostomy are described. The
      postoperative recovery is prompt with a rapid return of intestinal function and
      early discharge from the hospital. CONCLUSIONS: Laparoscopic ileostomy and
      colostomy are straightforward procedures that reduce postoperative discomfort and
      ileus, and reduce the length of hospital stay.

PMID- 8147615
TI  - The role of preoperative surgical staging in left upper lobe tumors.

PMID- 8147616
TI  - Ultra-long-gap esophageal atresia: how long is long?

PMID- 8147617
TI  - Is traumatic rupture of the aorta misunderstood?

PMID- 8147618
TI  - Cerebral effects of low-flow cardiopulmonary bypass and hypothermic circulatory
      arrest.
AB  - Although both hypothermic circulatory arrest (HCA) and low-flow cardiopulmonary
      bypass (CPB) are accepted techniques for the operative management of complex
      cardiovascular pathology, the potential for neurologic sequelae is still a
      concern. To assess the relative safety of these techniques, we compared cerebral
      hemodynamics and clinical outcome in two groups of puppies. Sixteen puppies
      underwent 45 minutes of either HCA or low-flow CPB (25 mL.kg-1.min-1) after
      cooling to 13 degrees C. Methodology included radioactive microsphere
      determination of cerebral blood flow; calculation of cerebral oxygen extraction
      (arteriovenous oxygen content difference) and consumption; measurement of glucose
      consumption, and determination of cerebrovascular resistance. Measurements were
      obtained at baseline (37 degrees C), 13 degrees C, and 30 degrees C and at 2, 4,
      and 8 hours after HCA or low-flow CPB. No neurologic deficits were observed in
      any of the survivors (15/16). In both groups, cerebral metabolic rate of oxygen
      was maintained at baseline or greater levels postoperatively. Cerebrovascular
      resistance rose slightly in the low-flow CPB group postoperatively in contrast to
      a marked elevation in the HCA group. During the period of high cerebrovascular
      resistance after HCA, cerebral metabolic rate of oxygen was maintained by
      increased oxygen extraction. After low-flow CPB, oxygen extraction was not
      significantly different from baseline, presumably because of less severe changes
      in cerebrovascular resistance. Glucose metabolism followed the same trends as
      oxygen metabolism in both groups. These data suggest that after HCA there is a
      vulnerable interval, lasting as late as 8 hours postoperatively, in which
      cerebrovascular resistance remains high and cerebral metabolism is maintained
      primarily by high oxygen and glucose extraction. Any additional stress during
      this interval (a decrease in arterial oxygen content or perfusion pressure) could
      result in cerebral injury.

PMID- 8147619
TI  - Ischemia-dependent efficacy of phosphodiesterase inhibition.
AB  - To evaluate the inotropic efficacy of phosphodiesterase inhibition in hearts with
      and without ischemic injury, 27 sheep were evaluated sonomicrometrically during
      incremental volume loading on right heart bypass. Contractility was assessed with
      the preload recruitable stroke work relationship. Active relaxation rate was
      estimated using the time constant of isovolumic pressure decay (tau). For
      nonischemic assessment, groups 1 and 2 (n = 6 each) underwent 45 minutes of
      vented perfusion after which milrinone was administered to group 1; group 2
      served as nonischemic controls. There was no detectable increase in preload
      recruitable stroke work or decrement in tau after milrinone administration.
      Groups 3 and 4 underwent 15 minutes of 37 degrees C ischemia (aortic cross
      clamping) followed by 30 minutes of vented reperfusion. Milrinone was then
      administered to group 3 (n = 7); group 4 (n = 8) served as ischemically injured
      controls. Inotropic and lusitropic effects were present (group 3 preload
      recruitable stroke work: 35.4 +/- 5.8 mJ.beat-1.100 g-1.mL-1 before milrinone to
      49.5 +/- 4.4 mJ.beat-1.100 g-1.mL-1 after milrinone [p < 0.05]; group 3 tau: 51.8
      +/- 5.5 ms before milrinone to 32.2 +/- 2.5 ms after milrinone [p < 0.02]).
      Although milrinone restored contractility and increased the rate of active
      relaxation in the postischemic hearts, there was no detectable inotropic effect
      in nonischemic hearts. In this model, milrinone augments contractility and
      relaxation in postischemic myocardium but offers little inotropic benefit in non
      ischemically injured hearts.

PMID- 8147620
TI  - Cardiac transplantation in infants and children.
AB  - Cardiac transplantation has become a more frequently used therapeutic modality
      for select cardiac pathology in infants and children. Since June 1986, 30
      pediatric patients (19 male and 11 female) ranging in age from 4 days to 15 years
      (11 < or = 1 month old) have undergone orthotopic cardiac transplantation at our
      institution. Indications included idiopathic cardiomyopathy (n = 8), hypoplastic
      left heart syndrome (n = 13), and other forms of complex congenital heart disease
      (n = 9). There have been four operative and three late deaths only in the groups
      with hypoplastic left heart syndrome and other forms of complex congenital heart
      disease. Cumulative survival is 77% after a mean follow-up of 30 months (range, 6
      to 77 months). Three operative deaths were attributable to pulmonary
      hypertension, and the other was due to pulmonary hemorrhage. Two late deaths were
      secondary to allograft rejection, and the third was due to infection. There has
      been uniform survival in the group with idiopathic cardiomyopathy, and
      intermediate-term survival rates are 78% and 62% in the groups with complex
      congenital heart diseases and hypoplastic left heart syndrome, respectively (p =
      0.15). Although longer-term results are necessary, orthotopic cardiac
      transplantation appears to be an acceptable mode of therapy for endstage heart
      disease in the pediatric age group and technically can be performed despite
      complex malformations of the great arteries or atria.

PMID- 8147621
TI  - Extended cervical mediastinoscopy: prospective study of fifty cases.
AB  - To assess the usefulness of extended cervical mediastinoscopy (ECM) in the
      staging of bronchogenic carcinoma, an ECM was performed prospectively in 50
      patients with bronchogenic carcinoma of the left lung. The ECM was used after
      evaluation of disease operability and computed tomographic findings, and was
      performed simultaneously with standard cervical mediastinoscopy. In ECM, using
      the same cervical incision as in a standard cervical mediastinoscopy, dissection
      is performed behind the anterior face of the sternum. The aortic arch is reached
      at the level of the origin of the innominate artery. The mediastinoscope is then
      passed by sliding it along the left anterolateral face of the aortic arch until
      it reaches the aortopulmonary window. Extended cervical mediastinoscopy was
      considered positive when a nodal biopsy result consistent with a neoformative
      process or direct invasion of the mediastinal structures was found. Four patients
      with positive standard cervical mediastinoscopy and negative ECM were excluded. A
      false negative ECM was defined as the presence of infiltrated adenopathies at the
      paraaortic level detected on postoperative histologic study. The ECM was positive
      in 5 patients in whom operation was contraindicated. Resectability in the
      remaining 41 patients was 97.6%. Postoperative pathologic study showed
      infiltrated adenopathy in 3 patients (2 subcarinal, 1 subaortic) accounting for
      40 true negatives (the subcarinal group is inaccessible by ECM). This study
      suggests that ECM has outstanding specificity (100%), sensitivity of 83.3%, and a
      diagnostic accuracy of 97.8%. A positive predictive value of 100% and a negative
      predictive value of 97.5% were also identified by this study.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8147622
TI  - Impact of mammary grafts on coronary bypass operative mortality and morbidity.
      Department of Veterans Affairs Cardiac Surgeons.
AB  - The internal mammary artery is frequently used as a coronary artery bypass graft
      conduit because of superior long-term patency. The purpose of this study was to
      determine if there was also an advantage to the internal mammary artery in terms
      of operative mortality and morbidity. The Department of Veterans Affairs Cardiac
      Surgery Database was reviewed for two separate time periods, April 1987 through
      March 1989 and October 1990 through September 1991. During these periods, 14,172
      patients underwent coronary artery bypass grafting. Univariate and multivariate
      logistic regression analyses were used to determine preoperative variables
      predictive of operative mortality and morbidity, with the independent variable of
      use of the internal mammary artery added to previously determined indicators. The
      total group was analyzed in risk quartiles according to expected mortality.
      Univariate analysis revealed an operative mortality of 6.8% in the early period
      and 6.5% in the latter period for the saphenous vein groups compared with 3.7%
      and 3.2%, respectively, for the internal mammary artery groups (p = 0.000).
      Multivariate analysis revealed an odds ratio of operative death with use of the
      internal mammary artery graft versus use of vein grafts of 0.78 during the first
      period and 0.72 during the second period, reductions of 22% and 28%,
      respectively. There were 29% and 37% reductions in the odds of operative
      mortality in the highest-risk quartile group of patients using the internal
      mammary artery graft. The odds ratio of developing mediastinitis with one
      internal mammary artery graft was 1.84 (p < 0.01) in the first time period and
      1.11 in the second time period (p = not significant). However, with multiple
      mammary bypass grafts, the odds ratios were 3.70 (p < 0.01) and 2.96 (p < 0.01)
      in the respective time periods. On the basis of this study, it is concluded that
      internal mammary artery grafts in addition to providing superior long-term
      patency also decreased operative mortality after adjustment for patient risk
      factors. Use of the mammary artery does not consistently increase operative
      complications with the exception of mediastinitis when both internal mammary
      arteries are employed.

PMID- 8147623
TI  - Enhanced preservation of acutely ischemic myocardium with transseptal left
      ventricular assist.
AB  - Mechanical support for acute regional ischemia without hemodynamic collapse may
      be achieved percutaneously with an intraaortic balloon pump (IABP) or with
      transseptal left ventricular assist (TLVA) while awaiting revascularization. The
      relative benefits of these two percutaneous transfemoral techniques for the
      treatment of ischemia were compared in a representative animal model. During 90
      minutes of regional coronary occlusion, four groups of 8 pigs were treated with
      either no support (control), IABP, TLVA, or both IABP and TLVA. Cardioplegic
      arrest for 30 minutes to simulate coronary grafting was followed by 180 minutes
      of global reperfusion on bypass. In all groups regional wall motion and
      interstitial pH in the area at risk were significantly depressed with ischemia,
      but wall motion fully recovered after reperfusion. However, histochemical
      staining of the area of necrosis/area at risk was significantly reduced with IABP
      versus control (20.2% versus 34.1%; p < 0.05) and further significantly reduced
      with TLVA and IABP + TLVA (10.7% and 6.7% versus IABP alone; p < 0.05). We
      conclude that in supporting even a modest-sized myocardial region at risk (12% of
      the left ventricle) the area that went on to infarction was significantly reduced
      with the use of TLVA over IABP. Regional wall motion and myocardial pH
      measurements did not reflect this difference in the early reperfusion period. The
      benefit of TLVA over IABP during more extensive or prolonged ischemia may have
      real clinical significance.

PMID- 8147624
TI  - Primary repair of ultra-long-gap esophageal atresia: results without a
      lengthening procedure.
AB  - Ultra-long-gap esophageal atresia, defined as a gap length of 3.5 cm or greater,
      has proved difficult to repair. When primary repair has been attempted, even with
      bougienage, circular myotomy, or intraabdominal esophageal mobilization to lessen
      anastomotic tension, leaks, anastomotic disruptions, and recurrent
      tracheoesophageal fistulas are frequent. Consequently, interposition grafts are
      commonly used. For long-term function the intact native esophagus should be
      preferable to an interposition graft or the consequences of circular myotomy.
      Therefore, even when an ultra-long gap is present, we have carried out a primary
      repair using our single-layer technique without myotomies. Since 1979, 8 of 58
      infants (14%) with esophageal atresia had gaps ranging from 3.5 to 6 cm. All had
      a primary repair with follow-up from 1 to 11 years. Despite severe anastomotic
      tension in all cases, there were no anastomotic leaks, disruptions, recurrent
      tracheoesophageal fistulas, or deaths. The tension, however, may have led to
      major gastroesophageal reflux in 5 of 8 patients (62.5%), all treated by a Nissen
      fundoplication, and a stricture in 4 of 8 infants (50%). Three strictures
      responded to dilation and one was resected. Now, all children are eating a normal
      diet for age. In conclusion, this technique has allowed primary repair of ultra
      long-gap esophageal atresia. Although the severe tension may contribute to
      strictures needing dilation and gastroesophageal reflux requiring fundoplication,
      primary repair resulted in a clinically functional native esophagus.

PMID- 8147625
TI  - Single-stage repair of distal aortic arch and thoracoabdominal dissecting
      aneurysms using aortic tailoring and circulatory arrest.
AB  - The adjuncts of profound hypothermic circulatory arrest and aortic tailoring are
      combined with standard graft replacement of the noncritical portions of the
      aorta. This combination permits single-stage replacement of the arch, thoracic,
      and abdominal aorta in patients with postdissection aneurysm. Reconstruction is
      begun with repair of the mid to distal aortic arch and Dacron graft replacement
      of the proximal descending thoracic aorta, usually under profound hypothermic
      circulatory arrest. The proximal graft is then cannulated and the patient
      partially warmed while the middle segment is "tailored." Aortic tailoring
      consists of longitudinal aortotomy and removal of the dissection membrane(s) from
      the distal third of the descending thoracic aorta to below the renal arteries.
      The aorta is then closed creating a single channel 2 to 3 cm in diameter and
      containing the origins of the important intercostal, lumbar, and visceral
      arteries. A Dacron graft is used to replace the infrarenal segment. Five patients
      have successfully undergone single-stage, total repair of the aorta including the
      arch, thoracic, and abdominal segments. All survival without paraplegia or
      significant visceral ischemia. Follow-up has not shown dilatation of the tailored
      segment. We believe that reduction in diameter of the tailored aortic segment and
      thus wall tension, growth of neointima on all luminal aortic surfaces, and active
      collagen deposition contribute to the success of this procedure.

PMID- 8147626
TI  - Should surgeons still be implanting pacemakers?
AB  - Cardiac pacing has undergone major changes in the areas of manpower, technology,
      and cost over the past 10 years. Arguments have been made to eliminate cardiac
      surgical involvement in pacing on the basis of these three areas of change:
      implantations are increasingly performed by nonsurgeons, surgeons have not kept
      up with the technologic advances in pacing, and consolidation of bradypacing
      resources is necessary during a time when reimbursement has declined
      significantly. This study examined two eras of pacing therapy at an institution
      where pacemaker implantation has always been performed by cardiothoracic
      surgeons. The purpose of the study was to critically analyze (1) the current role
      (if any) of cardiothoracic surgeons in delivery of pacemaker therapy and (2) the
      current results of cardiothoracic surgical involvement in pacemaker implantation.
      In 1,562 procedures performed between 1986 and 1992, the infection rate was 0.51%
      and the overall complication rate (both short-term and long-term) was 5.2%.
      During era 1 (1/1/86 to 6/30/89), 80% of implants were single-chamber and follow
      up was incomplete and dependent in many instances on the referring
      cardiologist/internist. For the implantations performed in the second era (7/1/89
      to 12/31/92) as part of an established Pacemaker Service, complete clinical and
      transtelephonic follow-up services were provided by this coordinated medical
      surgical approach. During era 2, 53.9% of implants were dual-chamber (79% during
      1992). Total and infectious complication rates remained low in era 2 despite this
      change in technology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147627
TI  - Potential application of p53 as an intermediate biomarker in Barrett's esophagus.
AB  - Diagnosis of the neoplastic progression in Barrett's esophagus using the
      histologic classification of dysplasia is frequently difficult. The tumor
      suppressor protein p53, when mutated, confers a promoter effect on cell growth.
      The purpose of this study was to evaluate the applicability of p53 as an
      intermediate biomarker of malignancy in Barrett's esophagus. Archival analysis of
      100 biopsy specimens of Barrett's esophagus and 10 esophageal adenocarcinomas
      were compared with 35 chronic esophagitis biopsy specimens. Immunocytochemistry
      using an anti-p53 monoclonal antibody was performed and elevated immunoreactivity
      quantitated microscopically. Data were analyzed using a logistic regression
      model. Significant p53 immunoreactivity occurred as follows: chronic esophagitis
      (0%), Barrett's esophagus without dysplasia (10%), with low-grade dysplasia
      (60%), with high-grade dysplasia (100%), and adenocarcinoma (70%). All cases of
      Barrett's esophagus were significantly immunoreactive when compared with the
      chronic esophagitis cases (p = 0.001). There was an increase in p53
      immunoreactivity as the histologic classification progressed toward
      adenocarcinoma (p = 0.001). Progression to high-grade dysplasia may be predicted
      based on p53 immunoreactivity. These findings suggest a role for p53 as an
      intermediate biomarker in Barrett's esophagus.

PMID- 8147628
TI  - Imaging strategies for vascular rings.
AB  - Thirty-nine patients have undergone operation for relief of tracheoesophageal
      compression resulting from vascular rings and related entities at the Mayo
      Clinic. Nineteen patients had a double aortic arch, 11 patients had a right
      aortic arch with an aberrant left subclavian artery, 5 patients had a left aortic
      arch with an aberrant right subclavian artery, 2 patients had a pulmonary artery
      sling, 1 patient had a right aortic arch with mirror-image branching and a left
      ligamentum arteriosum, and 1 patient had a left aortic arch, a right descending
      aorta, and a right ductus arteriosus. Diagnostic examinations included chest
      radiography, barium esophagography, angiography, and, more recently,
      transthoracic echocardiography, computed tomography, and magnetic resonance
      imaging. A comparison among the various diagnostic techniques used in 12 patients
      during the last 12 years showed that angiography (n = 7), magnetic resonance
      imaging (n = 5), and computed tomography (n = 3) were the most reliable, as they
      always accurately delineated the anatomy. However, in the 6 patients who
      underwent transthoracic echocardiography, 1 of whom was an older child and 2 of
      whom were adults, the vascular abnormality was described correctly only once; in
      the other 5 patients, the results were false-negative or the technique failed to
      visualize the relevant vascular structures sufficiently. Currently, magnetic
      resonance imaging is our imaging technique of choice for the delineation of the
      vascular and tracheal anatomy in patients suspected of having a vascular ring.

PMID- 8147629
TI  - Spontaneous closure of fenestrations in an interatrial Gore-Tex patch:
      application to the Fontan procedure.
AB  - The concept of the partial Fontan procedure, first described with the adjustable
      atrial septal defect (ASD) and more recently with the fenestrated technique, has
      become an accepted approach for the management of high-risk patients undergoing
      the Fontan procedure. Experience with both techniques has shown that a patent ASD
      placed in a prosthetic interatrial baffle may close spontaneously over a period
      of weeks to months. The mechanism and timing of spontaneous closure, as well as
      the effect of antiplatelet therapy on this process, are poorly understood. To
      better define this process, the interatrial septum of 15 mongrel dogs was excised
      and replaced with a fenestrated Gore-Tex (W.L. Gore, Flagstaff, AZ) patch.
      Postoperative echocardiography confirmed the patency of the ASD and left-to-right
      shunting. Animals were sacrificed 4 to 6 weeks postoperatively, or sooner if
      infection or other postoperative complications developed. Eight animals underwent
      no antiplatelet or anticoagulation therapy postoperatively, and 7 received
      antiplatelet therapy with aspirin. Patches were removed at the end of the study
      period and analyzed. By 6 weeks, all 2.7-mm and 4-mm holes had closed
      spontaneously in all animals that had not received antiplatelet therapy. The
      earliest closure occurred at 1 week. With antiplatelet therapy, hole closure was
      found to be delayed but not prevented, and was complete by 6 weeks in all but 1
      animal. Histologic examination of the explanted patches revealed that closure was
      accomplished primarily through the ingrowth of fibrous tissue, accompanied by an
      inflammatory cell infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147631
TI  - Pacing thresholds of temporary epicardial electrodes: variation with electrode
      type, time, and epicardial position.
AB  - We compared the variation in pacing thresholds of two widely used temporary
      pacing electrodes at different epicardial sites in 67 patients after coronary
      artery operations performed with either cardioplegia or ventricular fibrillation.
      In 33 patients, a bare, braided pacing wire (DW) was placed on the right
      ventricle and a Medtronic localized epicardial electrode (MED), on each
      ventricle. In the other 34 patients, the DW wire was placed on the right atrium
      and a MED electrode, on each atrium. Pacing thresholds were measured at the time
      of placement; at 1 hour, 6 hours, and 12 hours postoperatively; and daily for 4
      days. The pacing thresholds (mean +/- standard error of the mean) at implantation
      were as follows: DW wire = 0.93 +/- 0.08 V and MED electrode = 0.63 +/- 0.1 V in
      the ventricles and DW = 1.28 +/- 0.18 V and MED = 0.65 +/- 0.09 V in the atria.
      On the fourth postoperative day, the pacing thresholds were DW = 2.08 +/- 0.21 V
      and MED = 1.19 +/- 0.22 V in the ventricles and DW = 2.33 +/- 0.29 V and MED =
      1.04 +/- 0.09 V in the atria. The pacing thresholds of both types of wire
      increased significantly over time, but this deterioration was more pronounced
      with the braided wire both on the ventricle and on the atrium. The pacing
      threshold patterns were not affected by chamber side or mode of myocardial
      preservation. The braided ventricular wire failed to capture after 24 hours in 9
      of 30 patients, whereas the localized epicardial electrode captured in all
      instances (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147630
TI  - Safety and therapeutic effectiveness of reinfused shed blood after open heart
      surgery.
AB  - This prospective study was designed to determine whether use of nonwashed shed
      mediastinal blood exacerbated platelet and related hematologic dysfunctions after
      cardiopulmonary bypass, compared with the alternative use of autologous and
      homologous standard liquid preserved blood for volume support. Thirty-two
      patients undergoing cardiopulmonary bypass for open heart operations were
      randomized to receive either nonwashed shed mediastinal blood (group 1; n = 16)
      or liquid preserved packed red blood cells (group 2; n = 16) for transfusion
      therapy in the management of postoperative bleeding. Patient blood samples and
      bleeding times were obtained preoperatively, after cardiopulmonary bypass but
      before transfusions, 2 and 24 hours after transfusion, and on postoperative days
      2, 3, and 7. Group 1 patients received an average of 710 +/- 90 mL (range, 300 to
      1,700 mL) of nonwashed shed mediastinal blood containing significantly greater (p
      < 0.0001) amounts of fibrin degradation products and D-dimer protein. Of the
      hematologic, microaggregate, and plasma protein measurements performed, only the
      protein C level was significantly greater in group 1 (p < 0.05) after
      transfusion. Patient bleeding times were not significantly different between the
      groups at any of the time points, and the total postoperative blood loss was not
      different between the groups. There was a trend toward less need for homologous
      transfusion in group 1 (p < 0.1). This study documents the safety and ease of
      using nonwashed shed mediastinal blood as a primary blood volume support after an
      open heart operation.

PMID- 8147632
TI  - Reconstruction of the pulmonary artery in patients with lung cancer.
AB  - Between March 1990 and December 1992, we performed 17 resections and
      reconstructions of the pulmonary artery (PA) in patients with lung cancer. Three
      patients with intrapericardial infiltration of the PA underwent left
      pneumonectomy and PA angioplasty through a median sternotomy during
      cardiopulmonary bypass. The first patient survived in excellent general health
      for 25 months and then died of brain metastases; the second died of
      bronchopneumonia on postoperative day 24; and the third died of generalized tumor
      spread after 3 months. Fourteen patients had extrapericardial infiltration of the
      PA. They underwent sleeve upper lobectomy and PA reconstruction instead of
      pneumonectomy. In 6 patients we performed a sleeve resection of the PA, and in 8,
      the vessel was reconstructed using a patch of autologous pericardium. Two minor
      postoperative complications occurred. Three patients died after 14, 15, and 20
      months; the remaining 11 are alive and well 5 to 31 months after operation. We
      conclude that PA reconstruction associated with sleeve lobectomy is an
      advantageous alternative to pneumonectomy in select patients with lung cancer.
      Intraoperative indications, surgical technique, and perioperative management are
      crucial to achieve good results. Reconstruction of the main PA during
      cardiopulmonary bypass in association with left pneumonectomy can be performed
      successfully. The long-term results need further evaluation.

PMID- 8147633
TI  - Preperitoneal insertion of the HeartMate 1000 IP implantable left ventricular
      assist device.
AB  - During a 16-month period, 12 consecutive patients underwent insertion of a
      HeartMate 1000 IP left ventricular assist device in a preperitoneal pocket that
      separated the device from the abdomen. All patients were in cardiogenic shock
      awaiting heart transplantation. Preoperatively, the mean cardiac index was 1.6
      L.min-1.m-2, with 11 patients on intraaortic balloon pump support and 2 on
      extracorporeal membrane oxygenation. The pocket was formed below the rectus
      abdominis and internal oblique muscles and above the posterior rectus sheath. The
      pump fit easily in all patients. One patient died of progressive multiorgan
      failure. Four patients are still on support. Seven patients underwent successful
      transplantation after a mean duration of 55 days of support (mean pump index was
      3.1 L.min-1.m-2 during support). One patient had driveline revision because of an
      exit site infection but had successful transplantation. The pump was explanted
      without difficulty at each transplant operation. All patients having
      transplantation are alive and well. Preperitoneal insertion of the HeartMate left
      ventricular assist device can be safely performed and may avoid problems posed by
      intraabdominal left ventricular assist device insertion.

PMID- 8147634
TI  - Effects of pH and temperature on lung preservation: a study with an isolated rat
      lung reperfusion model.
AB  - After the rat lung was flushed with 40 mmol/L phosphate-buffered saline solution
      containing 160 mEq/L of sodium and the heart-lung block was immersed in the same
      solution for 6 hours, the lung was reperfused with diluted autologous blood and
      ventilated for 30 minutes. Pulmonary artery pressure, airway pressure, difference
      in oxygen tension between inflow and outflow perfusate, and wet to dry weight
      ratio of the tissue were determined. Lungs treated at pH 7.75 showed a
      significantly lower pulmonary artery pressure and wet to dry weight ratio than
      those treated at pH 7.26 or 7.96. Organs preserved at 10 degrees C showed a
      significantly lower pulmonary artery pressure than those preserved at 5 degrees
      or 15 degrees C. When the effect of smaller temperature variations was examined,
      the 12 degrees C group showed a significantly lower pulmonary artery pressure
      than the 10 degrees C group. Thus, the isolated rat lung reperfusion model
      appears to provide an efficient screening system to examine the preservation
      solution or other conditions for lung preservation. Under the present
      experimental conditions, the optimal pH and temperature for rat lung preservation
      seem to be 7.75 and 12 degrees C, respectively.

PMID- 8147635
TI  - Long-term results of polytetrafluoroethylene mitral annuloplasty.
AB  - Prosthetic rings are customarily used for mitral annuloplasty to plicate and
      reinforce the annulus and keep the annulus from further dilating. From July 1984
      to March 1992, mitral annular plication using polytetrafluoroethylene (PTFE)
      graft material was performed on 73 patients (age range, 15 to 69 years; mean,
      35.7 years) with mitral regurgitation. The cause of the mitral regurgitation was
      rheumatic in 50.7% and degenerative in 36.9% of the patients. After other repair
      procedures on the mitral valve apparatus had been performed, a PTFE graft (3 mm)
      was tailored to the length of the free edge of the anterior leaflet and then
      inserted at the posterior part of the mitral annulus between the commissures. The
      operative mortality was 2.7%. Follow-up ranged from 0.7 to 8.5 years (mean, 5.6
      years). Postoperative echocardiography confirmed that 94.2% of the survivors had
      either no or only mild mitral regurgitation with a large mitral valve area (2.7
      +/- 0.3 cm2) and almost no pressure gradient across the mitral valve or left
      ventricular outflow tract. Two patients successfully underwent redo PTFE mitral
      annuloplasty. Two patients died, one 15 and the other 20 months later, due to
      myocardial failure, with no mitral regurgitation. The event-free survival rate
      was 90% +/- 4% at 8 years. We conclude that PTFE mitral annuloplasty is an
      effective procedure that yields good long-term results.

PMID- 8147636
TI  - Lack of cardioplegia uniformity in clinical myocardial preservation.
AB  - Advances in myocardial preservation have led to improved patient survival after
      open heart operations. However, few studies have detailed the nature of national
      or regional patterns of cardioplegia use. To determine the regional pattern, all
      open heart surgery programs in Missouri were surveyed. During 1 year, it was
      found that cardioplegia was administered to 8,382 patients by 61 cardiothoracic
      surgeons at ten academic affiliated hospitals and 16 nonteaching hospitals. All
      cardioplegic solutions were hospital produced. Of 13 crystalloid solutions, 11
      differed from one another and eight were intracellular formulations. Of 28
      multidose blood-based cardioplegic solutions, there were 23 different mixtures.
      Most crystalloid (69%) and blood-based (89%) solutions differed substantially
      from commonly reported formulations. The incidences of the various additives to
      crystalloid solutions were as follows: bicarbonate, 92%; glucose, 69%; lidocaine,
      54%; mannitol, 46%; magnesium, 31%; calcium, 23%; methylprednisolone, 15%;
      heparin, 8%; and acetate, 8%. Of the common blood-based cardioplegic solution
      additives, the following incidences were observed: glucose, 79%; bicarbonate,
      43%; trishydroxyaminomethane, 36%; acetate, 29%; magnesium, 29%; procaine (or
      lidocaine), 25%; citrate-phosphate-dextrose, 18%; mannitol/albumin, 14%;
      nitroglycerin, 11%; glutamate/aspartate, 11%; calcium, 7%; insulin, 3%; and
      methylprednisolone, 3%. No calcium channel blocker or high-energy phosphate
      additives were reported. We conclude that many different cardioplegic admixtures
      that have not been tested experimentally are used routinely in clinical practice,
      presumably with acceptable results. Because the salutary effects of induced
      cardiac arrest and hypothermia may mask suboptimal solutions, further study of
      customized cardioplegia should be considered, particularly with regard to high
      risk patients.

PMID- 8147637
TI  - Effect of triiodothyronine on postischemic myocardial function in the isolated
      heart.
AB  - Thyroid dysfunction has been shown to have a significant impact on hemodynamic
      status and cardiac function. The purpose of this study was to determine the
      influence of triiodothyronine (T3) on cardiac functional recovery after ischemia
      in a dose-dependent manner. Postischemic functional recovery was assessed in
      isolated rabbit hearts mounted in a modified Langendorff preparation. Left
      ventricular systolic, diastolic, and peak developed pressures were measured
      before and after ischemia, and calculated as a percentage of preischemic
      function. Two cohorts of hearts were studied: the first was exposed to warm
      ischemia until a myocardial contracture of 4 mmHg was produced; the second cohort
      was exposed to warm ischemia until a contracture of 15 mm Hg was observed. In
      each cohort, T3 was added to the perfusion solution after ischemia in a
      physiologic concentration (2.5 x 10(-9) g/mL; 1 x T3), as well as ten times (2.5
      x 10(-8) g/mL; 10 x T3) and a hundred times (2.5 x 10(-7) g/mL; 100 x T3) the
      physiologic concentration. One group, given the carrier only but without T3,
      served as the control. Rabbit hearts exposed to a short period of ischemia (4
      mmHg diastolic contracture) showed increased recovery with 1 x T3 and 10 x T3.
      100 x T3 did not bring about improved left ventricular recovery versus that in
      the control group. Rabbit hearts in the 15 mm Hg-diastolic contracture cohort
      showed increased recovery with 10 x T3 but not with 1 x T3. 100 x T3 led to
      decreased recovery in this cohort versus that in the control group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8147638
TI  - Enhanced recovery of ischemic myocardium by combining percutaneous bypass with
      intraaortic balloon pump support.
AB  - Although percutaneous bypass (PB) can support the failing myocardium, regional
      ischemic damage may still occur beyond a coronary occlusion. This study sought to
      determine whether the addition of intraaortic balloon pump (IABP) support to PB
      would result in more optimal salvage of ischemic myocardium. In 30 pigs, the
      second and third diagonal vessels were occluded with snares for 90 minutes
      followed by 30 minutes of cardioplegic arrest and 3 hours of reperfusion with the
      snares released. During the period of coronary artery occlusion, 10 pigs were
      placed on PB, 10 pigs received PB plus IABP support, and 10 pigs received no
      support (the unmodified group). The hearts treated with the combination of PB and
      IABP support exhibited the highest wall motion scores (3.3 +/- 0.20 for the PB
      plus IABP group [p < 0.05 from the unmodified group and from the PB group];
      versus 1.40 +/- 0.30 for the PB group versus 1.37 +/- 0.33 for the unmodified
      group), the least tissue acidosis (change in pH, -0.30 +/- 0.2 for the PB plus
      IABP group [p < 0.05 from the PB group] versus -0.60 +/- 0.10 for the PB group
      versus -0.41 +/- 0.13 for the unmodified group), and the least area of necrosis
      (25% +/- 5% for the PB plus IABP group [p < 0.05 from the unmodified group and
      from the PB group]; versus 43% +/- 2% for the PB group [p < 0.05 from the
      unmodified group] versus 73% +/- 3% for the unmodified group).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8147639
TI  - Simultaneous graft replacement of the ascending aorta and total aortic arch for
      type A aortic dissection.
AB  - We performed simultaneous graft replacement of the total aortic arch and
      ascending aorta for type A aortic dissection with a patent false lumen extending
      through the arch into the descending or abdominal aorta. During the past 7 years,
      this procedure was performed in 42 patients (28 men and 14 women), aged 20 to 72
      years (mean age, 50 years). Nineteen patients underwent the procedure during the
      acute period, and 23 during the chronic period. The site of the initial intimal
      tear was the ascending aorta in 17 patients and the transverse aortic arch in 25
      patients. Artificial graft replacement was initially accomplished by proximal
      anastomosis, followed by open distal anastomosis, and finally by anastomosis of
      each of the three arch vessels. There were 3 hospital deaths (7.1%), 1 resulting
      from acute dissection (5.3%) and 2 from chronic dissection (8.7%). Among the type
      A dissections, total arch graft replacement has been indicated in the setting of
      rupture of the aortic arch, arch dissection, and Marfan's syndrome. However, with
      increasing experience in arch reconstructions and improvement in outcome, the
      indications could be expanded to include all type A aortic dissections with a
      patent false lumen in the descending aorta.

PMID- 8147640
TI  - Tumor recurrence in long-term survivors after treatment of carcinoma of the
      esophagus.
AB  - To evaluate the status of tumor recurrence and the possible factors relevant to
      tumor recurrence among patients who survived more than 5 years after subtotal
      esophagectomy for the treatment of squamous cell carcinoma of the esophagus, a
      total of 104 patients who received treatment between 1959 and 1986 were reviewed.
      In 18 of these 104 patients, local or distant tumor recurrence developed, for a
      tumor recurrence rate of 17.3%. Eleven (61.1%) of these 18 patients eventually
      died of carcinomatosis despite further radiotherapy or chemotherapy, or both, and
      4 patients with the disease are still alive. Three patients continue to survive
      after aggressive therapy was instituted for control of the locally recurrent
      tumor. Sixty-nine of the 104 patients are alive without tumor recurrence after
      the initial esophagectomy, and the remaining 17 patients died of miscellaneous
      causes. Tumor recurrence appears to be the most important factor affecting the
      prognosis in long-term survivors with resectable esophageal carcinoma. Among the
      11 patients who died of tumor recurrence, 10 died within 5 to 9 years of their
      esophagectomy. The incidence of various modes of tumor recurrence among these 18
      patients was as follows: blood-borne metastasis, 61%; lymph node recurrence, 33%;
      and locoregional organ recurrence, 33%. Factors that may be pertinent to a higher
      tumor recurrence rate include male sex, moderate to poor tumor differentiation,
      the presence of lymph node metastasis, and late stage of disease (stage IIb or
      worse). However, we could not find any statistical significance among these
      possible factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147641
TI  - Postpneumonectomy chylothorax.
AB  - Over a period of 22 years, chylothorax developed in 9 of 1,800 patients who
      underwent pneumonectomy. Two groups were identified. In group I (n = 5),
      accelerated opacification of the pneumonectomy space was noted, but the
      mediastinum remained shifted to the pneumonectomy site. No hemodynamic problems
      developed and their course was no different from that of other patients who had
      undergone pneumonectomy. In the second group (group II; n = 4), rapid
      opacification of the pneumonectomy space was accompanied by mediastinal shift
      away from the pneumonectomy site and by major hemodynamic and respiratory
      embarrassment. All 4 patients required surgical intervention to control the
      chylous leak.

PMID- 8147642
TI  - Cardiac operations in patients with end-stage renal disease.
AB  - Factors influencing the survival of 35 consecutive patients in end-stage renal
      disease who required 40 open heart surgical procedures over the past 8 years were
      studied. The mean age in these patients was 57.7 +/- 3 years (range, 32 to 77
      years); 74.3% of the patients were male; and the average duration of hemodialysis
      was 3.6 +/- 0.6 years. Twenty-nine myocardial procedures (20 of 29 for unstable
      angina), six valve replacements, and five combined procedures were performed. The
      actuarial survivals at 1 and 3 months, and at 1, 5, and 8 years were 90%, 85%,
      76%, 55%, and 43%, respectively. Based on the results of univariate analysis, the
      most significant predictor of both early and late mortality was New York Heart
      Association (NYHA) class IV congestive heart failure. The 5-year survival in the
      patients 60 years and older was less favorable than that in patients younger than
      60 years (45% versus 63%) (p < 0.05). The 5-year survival in the patients in NYHA
      class IV was only 27%, as compared to 63% in the patients in class II or III (p <
      0.001). All survivors have remained free of angina and 19 of the 21 survivors
      showed an improvement in their NYHA class. Four patients under 40 years of age
      have subsequently been able to undergo renal transplantation. Overall, these
      results justify proceeding with an open heart surgical procedure in dialysis
      patients, when needed, but before the onset of congestive heart failure.

PMID- 8147643
TI  - Twelve years' experience with the St. Jude Medical valve prosthesis.
AB  - Since July 1978, 1,284 patients have received the St. Jude Medical prosthesis
      (425 aortic, 636 mitral, and 223 double aortic-mitral), and the results in these
      patients were reviewed according to guidelines of the Society of Thoracic
      Surgeons. Follow-up was complete in 98%. Of 80 late deaths, 29% were valve
      related. The actuarial survival rate, including operative deaths, at 12 years was
      81.7% and 87.1%, respectively, for aortic and mitral valve replacement, and it
      was 82.6% at 11 years after double valve replacement. All patients were
      anticoagulated with warfarin to maintain the thrombotest value between 10% and
      25%, which is equivalent to between 2.8 and 1.6 times the control according to
      the international normalized ratio of the prothrombin time. The linearized rate
      of complication for aortic, mitral, and double valve replacement, respectively
      (expressed as the percent per patient-year), was as follows: structural
      deterioration, 0; non-structural dysfunction, 0.16, 0.30, and 0.20; valve
      thrombosis, 0.05, 0.09, and 0; thromboembolism, 1.35, 1.63, and 0.79;
      anticoagulant-related hemorrhage, 0.10, 0.18, and 0.10; and prosthetic valve
      endocarditis, 0.21, 0.06, and 0.20. Reoperation was performed in 16 patients. The
      freedom from reoperation rate at 12 years was 99.5% and 98.0% for aortic and
      mitral valve replacement, respectively, and it was 99.1% at 11 years for double
      valve replacement. Thus, during the 12-year follow-up in patient who received the
      St. Jude Medical prosthesis, the valve performed satisfactorily and with an
      acceptable risk of late complication even though patients were anticoagulated
      using a lower dose of warfarin.

PMID- 8147644
TI  - Bovine internal thoracic artery graft for myocardial revascularization: late
      results.
AB  - From May 1988 to March 1990, the bovine internal thoracic artery (ITA) graft, 3
      mm in diameter, was used for coronary artery bypass grafting in 29 patients with
      the approval of the Japanese Ministry of Health. Excluding three postoperative
      deaths and 6 patients who rejected postoperative angiography, 20 patients (13 men
      and 7 women; mean age, 62 years; range, 37 to 80 years) were followed up
      angiographically for up to 4 years. Sites of bovine ITA anastomosis were as
      follows: anterior descending, 4; circumflex, 5; and right coronary artery, 11.
      The mean bovine ITA graft blood flow measured by electromagnetic flowmeter was
      75.2 mL/min (range, 40 to 150 mL/min). During the mean follow-up of 45 months
      (range, 30 to 52 months), 12 patients underwent postoperative angiography once, 6
      patients twice, and 2 patients three times. It revealed 14 of 16 (88%) bovine ITA
      grafts were patent within 2 postoperative months. Three of 6 (50%) were patent at
      3 to 12 months, of which 2 patent grafts required balloon angioplasty for distal
      anastomotic stenosis. In 7 patients restudied later than 1 year (20, 24, 25, 44,
      48, 50, and 52 months), one of seven grafts (14%) was patent. There was stenosis
      (> or = 50%) at four distal and one proximal bovine ITA anastomotic sites, but no
      focal stenosis was found in the trunk at any period. There was one late death due
      to renal failure, one myocardial infarction, and one mild angina due to bovine
      ITA graft failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147645
TI  - Effect of cardiopulmonary bypass on early graft dysfunction in clinical lung
      transplantation.
AB  - The records of 100 lung transplant recipients (13 heart-lungs, 45 double-lungs,
      and 42 single-lungs) from September 1990 through April 1992 were reviewed to
      determine the role of cardiopulmonary bypass (CPB) in early graft dysfunction.
      Fifty-five patients requiring CPB (CPB group) for 186 +/- 54 minutes were
      compared with the 45 patients without CPB (no-CPB group). All of the heart-lung
      and en-bloc double-lung transplantations were performed under CPB, with pulmonary
      vascular lung disease the principal diagnosis, resulting in a significantly
      younger age population in the CPB group. All other donor- and recipient-related
      factors matched well in both groups. Of 38 bilateral single-lung
      transplantations, CPB was used in 18. In double-lung and heart-lung recipients
      gas exchange of the allografts was evaluated by the arterial/alveolar oxygen
      tension ratios at nine intervals during the first 72 hours. The mean
      arterial/alveolar oxygen tension ratio in the CPB group was 0.48 +/- 0.19,
      significantly lower than in the no-CPB group with 0.60 +/- 0.22 (p = 0.025). All
      patients had radiographic interpretation and scoring of pulmonary infiltrates
      from chest roentgenograms taken within 12 hours after reperfusion. The CPB group
      had more severe pulmonary infiltrates than the no-CPB group (p = 0.034).
      Prolonged intubation defined as 7 days or longer occurred significantly more
      often (29/55) in the CPB group than in the no-CPB group (8/45) (p = 0.003).
      Actuarial graft and patient survival at 1 month was better in the no-CPB group
      than in the CPB group (42/45 versus 44/55 [p = 0.05] and 43/45 versus 45/55 [p =
      0.033], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147646
TI  - Simplified subxiphoid placement of implantable cardioverter defibrillators using
      a posterior rectus pocket.
AB  - A simplified subxiphoid procedure using a single longitudinal epigastric incision
      and posterior rectus pocket for implantable cardioverter defibrillators was used
      in 100 patients. Through a single incision, ventricular patches are placed via a
      transverse pericardiotomy, and a pouch is created behind the rectus abdominis
      muscle in the left upper quadrant for placement of the implantable cardioverter
      defibrillator. Patients have minimal discomfort soon after operation, and the
      implantable cardioverter defibrillator generator is imperceptible to most.

PMID- 8147647
TI  - Aortic injury in vehicular trauma.
AB  - A 5-year retrospective study of 530 motor vehicle fatalities revealed 105 aortic
      injuries occurring in 90 victims. These were reviewed to determine the injury
      patterns, circumstances, and mechanisms involved. In addition, the survival time,
      the driver's age and sex, the time of day of the accident, and the blood alcohol
      level were considered. The aortic injuries consisted of 61 transections and 44
      tears (13% were multiple). Sixty-five percent of the injuries were located in the
      proximal descending aorta (66% of these were transections), 14% were in the
      ascending aorta and arch (33% of these were transections), 12% were in the distal
      descending aorta (more than 1 cm distal to the subclavian artery) (46% of these
      were transections), and 9% were in the abdominal aorta (56% of these were
      transections). Associated injuries consisted of multiple rib fractures (78%),
      liver lacerations (61%), head injuries (42%), first rib fractures (42%), splenic
      lacerations (36%), heart lacerations (34%), sternal fractures (28%), cervical
      spine fractures (26%), and thoracic spine fractures (20%). Death occurred within
      1 hour in 94% and within 24 hours in 99%. The impact was head-on in 62% of the
      accidents. The victim was the driver 74% of the time and male in 77% of the
      cases, and the blood alcohol level exceeded 0.1 mg/dL in 43%. Most aortic
      disruptions were complete transections of the proximal descending aorta,
      associated with serious injury to the thorax, and occurred in head-on collisions.
      Findings support a compression and upward thrust of the heart as a mechanism
      responsible for the aortic disruption.

PMID- 8147649
TI  - Review of blood transfusion practices in thoracic surgery.
AB  - Between September 1, 1989, and August 31, 1990, 516 patients were admitted to the
      Royal Brompton National Heart and Lung Hospital for thoracic operations. A
      prospective audit recorded the nature and extent of operation, the histologic
      diagnosis, and the number of units of blood prepared and transfused during
      hospitalization. Cross-matched blood was requested in 243 patients but only 16.1%
      of these received transfusion. In total, 1,295 units of whole blood or red cell
      concentrate were cross-matched and made immediately available in the operating
      suite at the time of operation. Only 322 units were administered (cross-match to
      transfusion ratio of 4.02:1). Almost half of the patients who received
      transfusions received 2 units or less, a third received 3 or 4 units, 10% between
      5 and 10 units, and 8.4% required more than 10 units during their hospital stay.
      The nature and extent of resection was an indicator of the need for transfusion.
      Other important predisposing factors included a previous thoracic operation,
      resection for inflammatory disease, decortication of empyema thoracis, chest wall
      resection, or thoracoplasty. Other thoracic procedures such as pleurodesis,
      pleurectomy, open lung biopsy, pectus correction, operation for bullous lung
      disease, and mediastinoscopy had a negligible transfusion requirement. The data
      suggest that understanding risk factors for transfusion requirements of patients
      undergoing thoracic surgical procedures should optimize present resources. This
      is critical when exploiting the limited availability of donated blood and blood
      products. Similarly, anticipation of transfusion requirements takes best
      advantage of manpower within the blood bank and minimizes unnecessary and
      avoidable blood wastage and expenditure.

PMID- 8147648
TI  - Hemodilution reduces early reperfusion injury in an ex vivo rabbit lung
      preservation model.
AB  - We sought to reduce early ischemia-reperfusion injury after lung preservation by
      an initial brief period of hemodilute reperfusion. Left lungs of New Zealand
      White rabbits were ventilated with room air and reperfused in an ex vivo
      ventilation-perfusion apparatus after 18 hours of storage at 10 degrees C. Lungs
      were randomly assigned to one of three groups (n = 6) according to the
      composition of initial reperfusate. In group 1 (control), preserved lungs were
      reperfused with whole blood for 20 minutes (hematocrit, 38%). In the experimental
      groups, blood was diluted to a hematocrit of 10% with Ringer's lactate (group 2)
      or low-potassium-dextran solution (group 3) for the first 10 minutes of
      reperfusion, followed immediately by whole blood for 10 minutes. Oxygen tension
      of left ventricular effluent at the end of the 20-minute assessment period was
      significantly higher in both hemodiluted groups (mean +/- standard error of the
      mean: group 2, 81.3 +/- 6.6 mmHg; group 3, 77.0 +/- 9.5 mmHg, versus Group 1,
      46.3 +/- 7.4 mmHg; p < 0.006). Similarly, mean tracheal airway pressure was
      reduced in the hemodiluted groups, suggesting improved compliance (group 2; 3.1
      +/- 0.3 mmHg; group 3, 2.8 +/- 0.6 mmHg; versus group 1, 6.5 +/- 1.4 mm Hg; p <
      0.05). An initial 10-minute period of hemodilute reperfusion appears to reduce
      early pulmonary ischemia-reperfusion injury in this 18-hour ex vivo rabbit lung
      preservation model.

PMID- 8147650
TI  - Cerebrovascular accident complicating extended cervical mediastinoscopy.
AB  - The safety and efficacy of staging cervical mediastinoscopy is well established.
      Extended cervical mediastinoscopy has been proposed as a safe and effective
      method of staging left upper lobe lung cancers. We report a case of
      cerebrovascular accident complicating extended cervical mediastinoscopy.

PMID- 8147651
TI  - Use of neurosurgical techniques for removal of a cardiac tumor.
AB  - A 6-week-old male infant with a capillary hemangioma of the right
      atrioventricular groove adjacent to the right coronary artery and conduction
      system underwent successful resection with the aid of microneurosurgical
      instrumentation. The technical challenge was thought to be analogous to that
      encountered by microneurosurgeons in their dissection of brain tumors.

PMID- 8147652
TI  - Schwannoma of the left atrium: diagnostic evaluation and surgical resection.
AB  - A case of primary benign schwannoma of the left atrium is reported. A 35-year-old
      man presented with new onset atrial fibrillation. Noninvasive evaluation revealed
      a 4 x 7-cm mediastinal mass either directly posterior to or involving the left
      atrium. The histologic diagnosis and specific location of the mass were
      established by incisional biopsy through a left thoracotomy. On cardiopulmonary
      bypass the tumor was resected by widely excising the posterior left atrium. The
      residual 20-cm2 left atrial defect was patched with pericardium. This unusual
      case illustrates that left atrial tumors originating near the pulmonary veins may
      be nonmyxomatous neoplasms of neural origin. Diagnosis may be difficult and
      require a surgical transthoracic approach.

PMID- 8147653
TI  - Mitral valve replacement using a cryopreserved mitral homograft.
AB  - Mitral valve replacement, using a cryopreserved mitral homograft, was performed
      in a 49-year-old patient with calcified mitral stenosis. Postoperative course was
      uneventful. Transesophageal echocardiography performed 6 months later showed
      normal function of the mitral homograft.

PMID- 8147654
TI  - Neisseria gonorrhoeae mycotic ascending aortic aneurysm.
AB  - Mycotic aneurysms of the ascending aorta are rare. We report the case of a 38
      year-old woman with systemic lupus erythematosus being treated with steroids who
      presented with a large Neisseria gonorrhoeae ascending aortic aneurysm. She was
      successfully treated with surgical resection of the aneurysm and prolonged
      postoperative antibiotic therapy.

PMID- 8147655
TI  - Pulmonary autograft failure caused by a relapse of rheumatic fever.

PMID- 8147656
TI  - Total gastrectomy in a patient with an in situ right gastroepiploic artery graft.
AB  - A 60-year-old man in whom coronary artery bypass grafting was performed with an
      in situ right gastroepiploic artery presented with a gastric adenocarcinoma 22
      months after myocardial revascularization. He underwent a total gastrectomy with
      preservation of the patent right gastroepiploic artery graft to the right
      coronary artery. Because of the difficulty of abdominal reoperations in patients
      with in situ right gastroepiploic artery grafts, surgeons must consider right
      gastroepiploic artery free graft or alternative conduits.

PMID- 8147657
TI  - Tricuspid valve replacement after orthotopic heart transplantation.
AB  - Atrioventricular valvular regurgitation is a known complication after cardiac
      transplantation. In this communication, we describe a case of progressively
      severe tricuspid insufficiency that ultimately necessitated tricuspid valve
      replacement. The patient has done well clinically since valve replacement, and a
      postoperative cardiac catheterization demonstrated normal right heart
      hemodynamics. A discussion of proposed causes and a review of the literature are
      provided.

PMID- 8147658
TI  - Salvage of infected truncus repair using rifampicin-impregnated gelatin-sealed
      graft.
AB  - An infant suffered sternal infection and ventricular septal patch dehiscence
      after a truncus arteriosus repair. Successful reoperation used rifampicin
      impregnated gelatin-sealed Dacron to repair the recurrent ventricular septal
      defect and replace the contaminated conduit. This was an effective solution to a
      potentially lethal surgical complication.

PMID- 8147659
TI  - Thoracoscopic clipping and ligation of a patent ductus arteriosus.
AB  - Several techniques of patent ductus arteriosus occlusion primarily by thoracotomy
      have been practiced. They have shown to be more reliable than nonsurgical
      procedures. Videothoracoscopy has been useful in several intrathoracic surgical
      procedures with faster recovery and minimal mortality and morbidity. We report 2
      patients with clipping and ligation of a patent ductus arteriosus by a
      thoracoscopic approach. This technique may be useful in children with a
      noncomplicated patent ductus arteriosus. It allows an easier recovery and causes
      less pain.

PMID- 8147660
TI  - Successful repair of congenital left ventricle-to-coronary sinus fistulas.

PMID- 8147661
TI  - Vertical muscle-sparing thoracotomy.
AB  - In our armamentarium of various thoracic incisions, we have incorporated a
      vertical skin incision with a muscle-sparing approach to gain access to the
      thorax. We find this incision gives excellent exposure, preserves function of the
      chest wall musculature, and leaves a cosmetically superior result.

PMID- 8147662
TI  - Two techniques for the control of cardiac bleeding.
AB  - Two new techniques effectively control local bleeding from the heart during heart
      operations. Both act by achieving local tamponade of the bleeding but through
      different mechanisms. In the first, a glove containing a sponge is placed against
      the bleeding site to provide local pressure. In the second, application of focal,
      high vacuum suction causes forceful apposition of adjacent soft tissue. These
      methods have stopped bleeding in 7 patients in whom conventional methods failed.

PMID- 8147663
TI  - Alternative technique for orthotopic heart transplantation.
AB  - An alternative technique for orthotopic heart transplantation is described. The
      principle consists of total excision of the recipient's right atrium with donor
      heart implantation performed using bicaval anastomoses; the left atrium is done
      in the standard fashion. This approach is technically simple and preserves the
      anatomic and physiologic function and integrity of the right atrium, especially
      the conduction system.

PMID- 8147664
TI  - Preservation of anterior leaflet chordae tendineae during mitral valve
      replacement.
AB  - Preservation of anterior mitral leaflet papillary muscle attachments during
      mitral valve replacement was achieved in 20 patients by excising the central
      portion of the anterior leaflet and suturing the rim of leaflet tissue containing
      marginal chordae to the remaining edge of leaflet attached to the left atrium.
      This closure tacks the chordae to the fibrous trigones, opens the subvalvular
      area, and avoids a potentially thrombogenic or obstructive redundant leaflet
      ridge along the rim of an inserted valve. The technique is simple, safe,
      reproducible, and teachable.

PMID- 8147665
TI  - A thoracoscopic peek: what did Jacobaeus see?
AB  - More than 80 years ago, Jacobaeus inserted a cystoscope into the pleural space of
      patients with pleural diseases to visually examine the pathology. Subsequently,
      he courageously inserted a galvanocautery instrument into the pleural space
      through a separate entry site to divide adhesions between the lung and chest wall
      under direct vision. This was done to establish therapeutic pneumothorax for
      patients with pulmonary tuberculosis. The discovery of effective antituberculosis
      chemotherapy eliminated the need for lung collapse therapy, and thoracoscopy was
      discarded as no longer useful. Today, the enthusiasm for thoracoscopic surgical
      intervention, both diagnostic and therapeutic, is a result of applied technologic
      innovations. Rediscovery of thoracoscopy is exciting and expands the vision for
      both diagnostic and therapeutic applications predicted by Jacobaeus.

PMID- 8147666
TI  - Pulmonary capillary hemangiomatosis: a clinicopathologic review.
AB  - Pulmonary capillary hemangiomatosis is a locally aggressive benign vascular
      neoplasm of the lung characterized by the presence of numerous cytologically
      benign thin-walled capillary-sized blood vessels proliferating diffusely through
      the pulmonary interstitium, in and around pulmonary vessels and airways.
      Pulmonary capillary hemangiomatosis is a rare disease characterized by pulmonary
      hypertension and a slowly progressive clinical course; it is frequently
      misdiagnosed clinically as primary pulmonary hypertension and veno-occlusive
      disease. The purpose of this review is to describe the clinical, radiologic, and
      histologic features of this rare form of pulmonary vascular neoplasm, which may
      present considerable diagnostic problems to both the clinician and the
      histopathologist. Fourteen cases of pulmonary capillary hemangiomatosis have been
      previously reported. In this review we describe the fourth case of pulmonary
      capillary hemangiomatosis in which the diagnosis was made antemortem, as well as
      the fourth to undergo lung transplantation.

PMID- 8147667
TI  - Esophageal diverticulum.

PMID- 8147668
TI  - Histology of internal mammary artery.

PMID- 8147669
TI  - Plasma C3a and C5a concentrations during cardiopulmonary bypass.

PMID- 8147670
TI  - Treatment of postthoracotomy supraventricular tachyarrhythmias.

PMID- 8147671
TI  - Swyer-James/Macleod's syndrome.

PMID- 8147672
TI  - Does endocardial laser revascularization induce "pseudovascular muscle tubes"?

PMID- 8147673
TI  - Blood contact during open heart operations: reducing the risk.

PMID- 8147674
TI  - Sternal wound dehiscence from peritoneal dialysis.

PMID- 8147675
TI  - Helicobacter pylori.
AB  - Helicobacter pylori is the cause of chronic active gastritis. It is integral to
      the pathogenesis of peptic ulcer disease and is epidemiologically linked to
      gastric cancer and lymphoma. Helicobacter pylori can be detected through a
      variety of invasive (urease testing, culture, or histologic diagnosis of
      endoscopic biopsies) and noninvasive (urease breath tests, serologic tests)
      diagnostic tests. It is now appropriate to detect and eradicate H pylori in
      patients with a peptic ulcer as the natural history of peptic ulcer disease is
      then markedly improved. At this time, there is no role for H pylori eradication
      in the prevention of gastric cancer; however, this concept is being actively
      investigated. There is no indication to treat patients who have H pylori and
      nonulcer dyspepsia or gastritis because eradication does not reliably affect
      their symptoms. Current regimens for eradication include bismuth, antibiotics,
      and antisecretory agents. Complex and poorly tolerated regimens (triple therapy)
      may no longer be necessary, as simpler regimens (omeprazole and amoxicillin or
      clarithromycin) appear to be as effective and better tolerated.

PMID- 8147676
TI  - Sexual dysfunction with antihypertensive drugs.
AB  - The relationship of antihypertensive drugs have a long history of association
      with sexual dysfunction; however, this relationship is poorly documented. There
      appears to be a higher rate of sexual dysfunction in untreated hypertensive men
      compared with normotensive men. Sexual dysfunction increases with age and is
      associated with physical and emotional symptoms. There are few studies assessing
      sexual dysfunction with female and African-American hypertensive patients. Sexual
      dysfunction is associated with impairment of quality of life and noncompliance.
      Since group data may hide individual drug effects, baseline data should be
      collected on all patients before initiating therapy with any antihypertensive
      agent. Although questionnaires may not provide objective information on sexual
      dysfunction, the response rate to direct questioning may be less than the
      response rate on a questionnaire and may be affected by the gender or race of the
      interviewer. Research protocols using a double-blind, placebo-controlled design
      should assess sexual dysfunction in men and women in a standardized fashion.

PMID- 8147677
TI  - Antihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide
      combination. A large multicenter study. Lisinopril-Hydrochlorothiazide Group.
AB  - OBJECTIVE: To test the antihypertensive and metabolic effects of lisinopril, 10
      mg/d (L); hydrochlorothiazide, 12.5 and 25 mg/d (H12.5 and H25); and its
      combination with lisinopril (L/H12.5 and L/H25) against placebo in patients with
      mild to moderate (stage I and stage II) hypertension. DESIGN: Multicenter, double
      blind, placebo-controlled outpatient study of 12 weeks' duration. PATIENTS: After
      4 weeks of single-blind placebo treatment, 505 patients whose sitting diastolic
      blood pressure was 100 to 114 mm Hg were randomized into the study--467 patients
      completed it (placebo, 71; L, 80; H12.5, 79; H25, 77; L/H12.5, 79; and L/H25,
      81). The patients were seen in the clinic every 2 weeks, where measurements of
      their sitting and upright blood pressure and heart rate were taken 24 +/- 2 hours
      after drug administration. Complete blood cell counts with differential cell
      counts, blood chemistry studies, urinalyses, and electrocardiograms were done at
      baseline and during the study. Roentgenograms were done once at baseline.
      RESULTS: Compared with placebo, all drug regimens decreased sitting and upright
      blood pressure (P < .001) and had no effect on sitting and upright heart rate.
      The greatest effect was obtained with the combinations of L/H12.5 and L/H25.
      There was no difference between L/H12.5 and L/H25 or between H12.5 and H25. There
      were no serious clinical side effects except cough, which was slightly higher
      with L, L/H12.5, and L/H25. The only metabolic side effects were in serum
      potassium level, which was lower with H25 (P < .01), and serum glucose level,
      which was higher with H25 and L/H25 (P < .01). CONCLUSIONS: The data suggest that
      (1) monotherapy of hypertension with L, H12.5, H25, L/H12.5, and L/H25 was
      effective and well tolerated; (2) the best results were achieved with L/H12.5 and
      L/H25; (3) lower doses of hydrochlorothiazide either alone or in combination with
      lisinopril were equipotent with higher doses and were free of metabolic side
      effects.

PMID- 8147678
TI  - The importance of mammographic screening relative to the treatment of women with
      carcinoma of the breast.
AB  - BACKGROUND: The use of mammographic screening for the early detection of breast
      cancer has been shown to reduce the mortality from breast cancer. However, the
      impact of mammographic screening relative to the local treatment of the breast
      (ie, breast-conservation treatment vs mastectomy) is not well established.
      METHODS: An analysis was performed of 206 newly diagnosed and treated breast
      cancers in 201 women identified in 1989 from a health maintenance organization
      (US Healthcare, Blue Bell, Pa). The 206 breast cancers were evaluated for
      eligibility for and actual local treatment of the breast with breast-conserving
      surgery and definitive breast irradiation as a function of mammographic screening
      for the early detection of breast cancer. RESULTS: Eligibility for local
      treatment of the breast with breast-conserving surgery and definitive breast
      irradiation was significantly increased for the breast cancers detected in women
      who had undergone mammographic screening compared with the breast cancers
      detected in women who had not undergone mammographic screening (88% vs 60%,
      respectively; P < .0001). For the breast cancers that were eligible on chart
      review for treatment with breast-conserving surgery and definitive breast
      irradiation, there was no significant difference in the actual local treatment of
      the breast with breast-conserving surgery and definitive breast irradiation for
      the eligible breast cancers detected in women who had undergone mammographic
      screening compared with the eligible breast cancers detected in women who had not
      undergone mammographic screening (44% vs 37%, respectively; P = .40); however,
      there was a statistically significant difference for the subgroup of women aged
      50 years or more (49% vs 21%, respectively; P = .016). CONCLUSIONS: These results
      show that breast cancers detected in women who had undergone mammographic
      screening were more likely to be eligible for breast-conserving surgery and
      definitive breast irradiation compared with breast cancers detected in women who
      had not undergone mammographic screening. For women aged 50 years or more, there
      was a significant increase in the use of breast-conserving surgery and definitive
      breast irradiation for eligible breast cancers detected in women who had
      undergone mammographic screening compared with eligible breast cancers detected
      in women who had not undergone mammographic screening.

PMID- 8147679
TI  - Osteomyelitis associated with pressure sores.
AB  - BACKGROUND: Pressure sores may be associated with underlying osteomyelitis that
      is difficult to differentiate clinically from infection or colonization of
      adjacent soft tissue. Cultures of bone specimens are frequently contaminated with
      organisms residing in adjacent soft tissue. The three objectives of this cohort
      study were to (1) determine the accuracy of clinical evaluation for
      osteomyelitis; (2) evaluate the potential role of quantitative cultures of bone
      in differentiating osteomyelitis from soft-tissue infection or colonization; and
      (3) assess the impact of treating osteomyelitis on the outcome of pressure sores.
      METHODS: Thirty-six patients with pressure sores related to spinal cord injury or
      cerebrovascular accident underwent clinical evaluation for osteomyelitis,
      followed by percutaneous needle biopsy of bone. Routine semiquantitative and
      quantitative, aerobic and anaerobic cultures of bone specimens were performed.
      Pathologic examination of bone tissue was used as the standard criterion for
      diagnosing osteomyelitis. RESULTS: Six (17%) of 36 patients were diagnosed by
      pathologic examination as having osteomyelitis. The sensitivity and specificity
      of clinical evaluation were 33% and 60%, respectively. When positive,
      quantitative bone cultures yielded a similar number of bacterial isolates and a
      comparable range of bacterial concentration in patients with osteomyelitis vs
      those without osteomyelitis. Pressure sores healed in all six patients with
      osteomyelitis after appropriate therapy. CONCLUSIONS: Clinical evaluation for
      osteomyelitis is often inaccurate. Pathologic examination of bone tissue is
      required for definitive diagnosis of osteomyelitis. Quantitative bone cultures do
      not help differentiate osteomyelitis from infection or colonization of adjacent
      soft tissue. It is possible that treatment of osteomyelitis may improve the
      outcome of associated pressure sores.

PMID- 8147680
TI  - Physician discretion and racial variation in the use of surgical procedures.
AB  - BACKGROUND: Racial variation in the use of surgical procedures raises concern
      about equitable access. The goal of our study was to examine racial differences
      in utilization across a broad range of procedures in Massachusetts and to assess
      whether racial variation is related to physician discretion. METHODS: We obtained
      fiscal year 1988 hospital discharge data for all Massachusetts residents,
      identified 10 clinically important surgical procedures, and calculated age- and
      sex-adjusted rate ratios for white and black patients. Level of discretion was
      determined by using a modified Delphi technique. RESULTS: Whites had higher rates
      for eight procedures (abdominal aortic aneurysm repair, appendectomy, cardiac
      valve replacement, carotid endarterectomy, cholecystectomy, lumbar disk
      procedures, open reduction/internal fixation of the femur, and tonsillectomy) and
      lower rates for two procedures, hysterectomy and prostatectomy. Of the eight
      procedures for which utilization was higher among whites, four were ranked as
      moderate- or high-discretion procedures and four were ranked as low-discretion
      procedures. Hysterectomy, the only procedure for which utilization was
      substantially higher among blacks (white:black rate ratio < 0.90), was ranked as
      a high-discretion procedure. CONCLUSIONS: With the exception of hysterectomy and
      prostatectomy, procedure rates for whites were greater than those for blacks for
      a wide range of surgical procedures. Racial variation exists for low-discretion
      procedures as well as for those associated with moderate and high discretion.
      Variation among low-discretion procedures that is not explained by medical need
      suggests the possibility of race-related differences in access to care or in the
      way patients and physicians make clinical decisions.

PMID- 8147681
TI  - Cost-effectiveness of screening for hereditary hemochromatosis.
AB  - BACKGROUND: Recent studies have estimated the prevalence of hereditary
      hemochromatosis to be 3 to 8 per 1000. Early detection and treatment can prevent
      disease manifestations and normalize life expectancy. We used decision analysis
      techniques to determine whether screening the population at large for hereditary
      hemochromatosis would be cost-effective. METHODS: We constructed a model to
      compare the cost and outcome of a strategy of performing screening transferrin
      saturation tests on cohorts of 30-year old men with that of awaiting symptomatic
      disease. Baseline estimates of disease prevalence and complication rates were
      based on the published literature. Costs of treatment were estimated based on
      prevailing local costs. Sensitivity analyses were then conducted to determine
      which variables had the most significant impact on the decision to screen.
      RESULTS: At our baseline estimates, the decision to screen was found to be a
      dominant strategy and resulted in cost saving. Sensitivity analysis showed that
      four variables had the most significant impact on the decision to screen: (1) the
      prevalence of hereditary hemochromatosis, (2) the probability of developing
      disease manifestations, (3) the cost of the screening test, and (4) the discount
      rate. Screening was a dominant strategy for asymptomatic men provided that the
      prevalence of hereditary hemochromatosis was at least 3 per 1000, the probability
      of developing disease manifestations was greater than 0.4, the test cost was less
      than $12, and the discount rate was less than 3%. Using more pessimistic
      estimates, the cost per life year saved was still less than that considered
      acceptable for many common medical interventions. CONCLUSION: Screening for
      hereditary hemochromatosis has a favorable cost-effectiveness ratio over a wide
      range of assumptions. We recommend that practitioners consider including a serum
      transferrin saturation test in their routine screening for asymptomatic white
      men.

PMID- 8147682
TI  - Bedside assessment of skin-fold thickness. A useful measurement for
      distinguishing Cushing's disease from other causes of hirsutism and
      oligomenorrhea.
AB  - BACKGROUND: The known catabolic effects of glucocorticoid excess on protein
      metabolism prompted us to devise a method to assess this measure in reproductive
      aged females with Cushing's disease. Since collagen protein is a major component
      of skin, decreased abundance of this protein should cause a reduction in skin
      fold thickness. To determine whether skin-fold thickness is useful as an added
      tool in the diagnosis of Cushing's disease, we compared this value in female
      patients with Cushing's disease with those who presented with a similar set of
      symptoms. METHODS: This open prospective study was conducted in an endocrinology
      clinic at a tertiary care center. The study population consisted of 88 females in
      the reproductive age group who presented to the clinic with hirsutism,
      oligomenorrhea, and/or obesity. Measurement of skin-fold thickness, body mass
      index, Ferriman-Gallwey index, and serum testosterone were performed in all
      patients. RESULTS: Skin-fold thickness in the patients with Cushing's disease was
      1.5 +/- 0.2 mm (range, 1.0 to 1.8 mm). This value was significantly (P < .01)
      lower than that in controls or subjects with other disorders that have a similar
      set of presenting symptoms. CONCLUSIONS: Bedside assessment of skin-fold
      thickness is an easy, low-cost, and noninvasive test for distinguishing Cushing's
      disease from disorders with similar presenting symptoms in females of
      reproductive age. Assessment of skin-fold thickness should be used as an adjunct
      to current physical and biochemical study of patients with symptoms suggestive of
      Cushing's disease.

PMID- 8147683
TI  - Maternal hypothyroidism during early pregnancy and intellectual development of
      the progeny.
AB  - OBJECTIVE: To investigate whether maternal hypothyroidism before the onset of
      fetal thyroid function influences mental development of the offspring. DESIGN: We
      examined IQs in children in whom the mothers had been hypothyroid during early
      pregnancy (group 1). The IQs were compared with those of siblings who were not
      exposed to maternal hypothyroidism during gestation (group 2). PATIENTS: Group 1
      consisted of eight children. Mothers were examined for thyroid status during the
      fifth to 10th gestational weeks and were found to have distinctly low thyroxine
      levels and high thyrotropin levels; the levels became normal after thyroxine
      supplementation by 13 to 28 weeks of gestation. Seven of the eight children had
      nine siblings who had not been exposed to maternal hypothyroidism during
      gestation (group 2). Ages at examination were 4 to 10 years in group 1 and 4 to
      15 years in group 2. RESULTS: All children in group 1 showed normal IQs. There
      was no significant difference in the mean IQ between the children in group 1 who
      had siblings (112 +/- 11) and their siblings in group 2 (106 +/- 8). Even the
      subject whose mother had had the lowest thyroxine level (free thyroxine, 2.3
      pmol/L) had an IQ similar to that of his sibling. CONCLUSION: These data provide
      evidence against the presence of adverse effects of maternal hypothyroidism
      during early pregnancy on the subsequent mental development of the offspring.

PMID- 8147684
TI  - Evidence of intraprison spread of HIV infection.
AB  - BACKGROUND: Individuals entering prison are known to have high rates of human
      immunodeficiency virus (HIV) infection, and inmates are known to engage in high
      risk behavior. This suggests the potential for intraprison spread of HIV
      infection, but this has not been documented. METHODS: All prisoners (N = 556) in
      the Florida Department of Corrections who had been continuously incarcerated
      since 1977 were identified. The medical records of these prisoners were reviewed
      to determine whether they had been tested for HIV infection and, if tested,
      whether the results were positive. Results were considered positive if there were
      reactions to two enzyme-linked immunosorbent assays confirmed by Western blot
      assay. If an individual tested positive, the medical record was reviewed to
      determine whether the patient had been treated for conditions consistent with HIV
      infection. RESULTS: Eighty-seven of the 556 prisoners had undergone testing for
      HIV infection. Of the tested inmates, 18 (21%) were found to be positive for HIV
      infection. Eight of these individuals had no HIV-related conditions, and 10 had
      HIV-related symptoms. CONCLUSIONS: The results present strong evidence for
      intraprison transmission of HIV infection. Given that most inmates serve
      relatively short sentences, there is a strong possibility that prison-acquired
      HIV infection will be carried into the "free world." Preventive programs in
      prisons may be very important in controlling HIV infection in our society.

PMID- 8147685
TI  - The Ides of March. The match 1993 in perspective.
AB  - BACKGROUND: The total number of US medical school graduates who selected
      categorical programs in internal medicine in this year's match fell by 7.9%.
      Consequently, the program fill rate for US graduates declined for the eighth
      consecutive year, from 55.9% to 53.1%. Preliminary positions and international
      graduates continue to increase, though questions remain whether these residents
      serve as good role models to encourage student interest in internal medicine.
      METHODS: We reviewed the 1993 National Resident Matching Program data and several
      curricular reforms implemented in our internal medicine clerkship and residency
      program to evaluate whether such reform might enhance interest in general
      internal medicine. RESULTS: Reform in our internal medicine clerkship curriculum
      included increased emphasis on problem-based learning and exposure to generalist
      role models. This resulted in substantial increases on the average miniboard
      examination and a 22% increase in the number of students pursuing residency in
      internal medicine from the previous year. Residency curricular reform centered
      around enhanced ambulatory care teaching along with improved exposure to
      generalist role models. This resulted in a gradual increase in the number of
      residency graduates who were staying in general internal medicine from 21% in
      1991 to 40% in 1993. CONCLUSIONS: Innovative curricular changes in our internal
      medicine clerkship and residency programs have led to enhanced interest in
      general internal medicine. Although our results are preliminary, such change is
      necessary, not only to continue program excellence, but for simple survival.

PMID- 8147686
TI  - Lp(a) lipoprotein is an independent, discriminating risk factor for premature
      peripheral atherosclerosis among white men.
AB  - BACKGROUND: Elevated plasma levels of Lp(a) lipoprotein have been linked to the
      development of premature atherosclerosis in the coronary circulation (coronary
      artery disease [CAD]). Although Lp(a) lipoprotein has been implicated as a risk
      factor for premature atherosclerosis in other locations, the patient populations
      described were not carefully screened for the coexistence of premature CAD. The
      purpose of this prospective study was to determine whether carefully screened
      patients with premature peripheral vascular disease (PVD) have elevated plasma
      levels of Lp(a) lipoprotein and to test the relative strength of Lp(a)
      lipoprotein level as a risk factor for premature PVD. METHODS: We studied 55
      consecutive white men with premature PVD (onset at 45 years of age or earlier)
      presenting to our vascular laboratory. Study subjects were substratified into 17
      with PVD only and 38 with combined PVD and CAD (PVD + CAD). Two comparison groups
      included 26 age-matched white men with premature CAD recruited from the
      Cardiology Service after cardiac catheterization and 32 age-matched white male
      controls recruited from outpatient clinics. RESULTS: Mean plasma apolipoprotein B
      100 levels were higher in the CAD group than in controls (P = .013). Mean plasma
      Lp(a) lipoprotein levels were higher among the 17 patients with PVD only than
      among controls (P = .008). The covariance-adjusted mean Lp(a) lipoprotein levels
      were higher among all 55 patients with PVD than among controls (P = .014).
      Logistic regression analysis demonstrated two variables to be significantly
      related to premature PVD: Lp(a) lipoprotein level greater than 30 mg/dL (odds
      ratio, 3.9; 95% confidence interval, 1.1 to 13.7) and apolipoprotein B level
      greater than 95 mg/dL (odds ratio, 3.2; 95% confidence interval, 1.0 to 10.0).
      CONCLUSIONS: Lp(a) lipoprotein level is an independent, discriminating risk
      factor for premature PVD among white men.

PMID- 8147687
TI  - Pseudotumor cerebri. A complication of catheter-induced subclavian vein
      thrombosis.
AB  - Pseudotumor cerebri is frequently the only clinical clue to the presence of
      cerebral venous thrombosis, a potentially devastating condition. We report a case
      of pseudotumor cerebri associated with thrombosed dural venous sinuses caused by
      propagation of a catheter-related subclavian vein thrombus. The findings and
      clinical course in this case alert us to a complication of central venous
      catheter use that responds well to treatment if recognized early.

PMID- 8147688
TI  - Stress, a gift to doctors.

PMID- 8147689
TI  - Hepatitis A and health care personnel.

PMID- 8147690
TI  - Possible nafcillin-warfarin interaction.

PMID- 8147691
TI  - Informed consent--not institution protection.

PMID- 8147692
TI  - What patient with essential hypertension should receive antihypertension drug
      therapy?

PMID- 8147693
TI  - Parvalbumin immunoreactivity in the telencephalic hemispheres of the tench, Tinca
      tinca.
AB  - The distribution of parvalbumin immunoreactivity in the telencephalic hemispheres
      of the tench (Tinca tinca L.) was studied using a monoclonal antibody and the
      avidin-biotin immunoperoxidase method. A wide distribution of immunoreactive
      structures was found in both dorsal and ventral areas of the telencephalic
      hemispheres. Normally, the parvalbumin-immunostained neurons in the dorsal area
      were smaller, more weakly stained, and more scattered than those in the ventral
      one. In the dorsal area, parvalbumin-immunoreactivity was observed in practically
      all divisions. The highest density of positive somata was found in the lateral
      nucleus. Density of stained fibres was generally low. Labelling in the ventral
      area appeared in the ventral and dorsal nuclei, with a high density of both
      immunoreactive fibres and cell bodies. Neurons were seen close to the ventricle,
      arranged in two groups of neurons with different sizes and morphologies. The
      distribution and morphological characteristics of the parvalbuminergic cells were
      similar to those of previously described GABAergic elements, suggesting a
      possible colocalization of both substances in the teleost telencephalon, as it
      has been observed in different telencephalic areas of land vertebrates. On the
      other hand, significant differences were seen between the distribution of
      parvalbumin in the telencephalic hemispheres of the tench in comparison with its
      distribution pattern in supposed homologous structures of the forebrain of
      amniotes.

PMID- 8147694
TI  - Nicotinamide-adenine-dinucleotide-phosphate diaphorase-positive neurons and
      fibers in the nucleus olfactorius anterior of the rat.
AB  - The distribution patterns of NADPH-diaphorase activity in the nucleus olfactorius
      anterior (NOA) and anterior commissure (AC) of the rat were described using an
      histochemical technique. In the lateral, dorsal, ventral, medial and posterior
      subdivisions of the NOA we have demonstrated heavily stained elements (neurons
      and processes), and slightly labelled cell bodies. The neurons were mainly
      located in the inner zone of these subdivisions. However, in the external
      subdivision (NOAe) strongly stained fibers and weakly labelled cell bodies were
      present. The NOA transitions areas showed the same NADPH-diaphorase activity
      distribution patterns as those of the corresponding NOA subdivisions. In the AC
      we described scarce NADPH-diaphorase positive fibers parallelly oriented to the
      unstained commissural fibers, and scattered stained neurons.

PMID- 8147695
TI  - The hypothalamocerebellar projection in the cat: branching and nuclear
      termination.
AB  - The hypothalamic projection to the cerebellar nuclei and cortex in the cat was
      studied by means of retrograde transport of wheat germ agglutinin-horseradish
      peroxidase complex and various fluorescent tracers. The hypothalamocerebellar
      nuclear projection originates from various parts of the posterior hypothalamus
      and reaches mainly the ipsilateral fastigial and interposed nuclei, but all
      nuclei receive some hypothalamocerebellar fibres. It appears from our double
      labelling experiments that at least one half of the hypothalamocerebellar nuclear
      neurones by means of axon collaterals also projects to the cerebellar cortex.
      Experiments with depositions of fluorescent tracers in both cerebellar
      hemispheres show that some hypothalamocerebellar fibres branch to reach different
      parts of the cerebellar cortex. Previous studies have shown that
      hypothalamocerebellar axons may be branches of hypothalamic efferents to other
      sites. However, experiments with combined fluorescent tracer depositions in the
      cerebellum and hippocampus gave no evidence for hypothalamic neurones with axon
      collaterals to both these regions.

PMID- 8147696
TI  - Sleep deprivation in the rat at different ambient temperatures: effect on sleep,
      EEG spectra and brain temperature.
AB  - To investigate the relationship between thermoregulation and sleep regulation,
      rats were sleep-deprived for 3 hours at two different ambient temperatures. Sleep
      deprivations (SD) were performed at 23 degrees C (SD-23) and at 32 degrees C (SD
      32) in the beginning of the 12-h light period in animals chronically implanted
      with ECoG and EMG electrodes, and with epidural and hypothalamic thermistors. SD
      32 enhanced cerebral temperature more than SD-23 at both brain sites. The SD
      induced hyperthermia was followed by a fall of brain temperature below baseline.
      During recovery from either SD procedure, waking was reduced and sleep continuity
      increased. REM sleep was increased after SD-32. EEG slow-wave activity (spectral
      power density in the 0.75-4.0 Hz band) exceeded the baseline level in the first 3
      h interval of recovery; however, the effects of SD-23 and SD-32 did not differ.
      In the same time interval, power density in the 1.25-1.5 Hz bin as well as in
      some bins in the theta and alpha band was higher after SD-32 than after SD-23.
      The increase in hypothalamic temperature during SD did not correlate with the
      increase in SWA during recovery. It is concluded that even a brief SD has major
      repercussions on recovery sleep whereas the extent of cerebral hyperthermia
      during SD is only a minor factor.

PMID- 8147697
TI  - Histochemical fiber composition of cat's tail muscles.
AB  - A histochemical analysis was performed on the activity of myofibrillar ATPase
      following preincubation at pH 10.3 with NADH-diaphorase in the cat tail muscles
      (ECM; extensor caudae medialis, ECL; extensor caudae lateralis, ACE; abductor
      caudae externus, ACI; abductor caudae internus, FCL; flexor caudae longus, and
      FCB; flexor caudae brevis). Muscles contained three types of muscle fibers: FG
      (fast-twitch glycolytic) showed high reaction of myofibrillar ATPase staining and
      low reaction in NADH-diaphorase staining; FOG (fast-twitch oxidative glycolytic)
      showed high reaction in myofibrillar ATPase staining and high reaction in NADH
      diaphorase staining; and SO (slow-twitch oxidative) showed low reaction in
      myofibrillar ATPase staining and high reaction in NADH-diaphorase staining. All 6
      tail muscles were composed of these three types of fibers, but proportions
      differed in each tail muscle. Proportions of SO and FG fibers were highest in ECL
      (SO: 38.6 +/- 2.3, S.D. %) and ACI (FG: 59.2 +/- 5.0%), respectively. The
      diameters of the fibers were also measured (SO; 50.47 +/- 3.12, FOG; 58.18 +/-
      2.78, FG; 70.91 +/- 3.40, S.D. microns).

PMID- 8147698
TI  - [Drug fatalities with cadaver dumping].
AB  - 7 cases of "dumping" of the bodies of drug addicts are reported. Circumstances of
      the case, findings at the scene, autopsy findings and confessions raised already
      the suspicion that the bodies were not found at the scene of death. In 5 cases
      the "dumping" of the bodies was outside, in 2 cases inside a house.
      Identification of the bodies was always easy, since personal papers (passport,
      identity card) were still present and no attempts were made to prevent
      identification. The prevalent motivation for "dumping" seems to be not to be
      identified as drug addict or dealer or to be brought in connection with the death
      of drug addicts.

PMID- 8147699
TI  - [Unusual injection site in a drug fatality in prison].
AB  - A lethal heroin-intoxication of a prisoner with localization of hardly detectable
      injection marks on the frenulum praeputii is reported. An extensive external
      examination in particular in cases of death in jail or of drug addicts is
      necessary to detect unusual signs of intravenous drug addiction.

PMID- 8147700
TI  - [Fatal gunshot injuries in Hamburg 1966-1991].
AB  - Deaths by fire-arms investigated at the Institute for Legal Medicine of the
      University of Hamburg were analyzed retrospectively since 1966. Among 70,000
      deaths (33,000 autopsies) there were 838 fatalities caused by gunshots (about 30
      cases per year). One third were classified as homicides, the others as suicides,
      only 3% as accidents. Almost the entire number of suicides was committed by men
      (relation male:female 20:1), whereas the proportion of women was higher among the
      homicides (ratio male:female 3:1). Details referring to the age of the victims,
      profession-coherence, alcohol-influence, capacity to act and survival-time are
      analyzed. The kinds of arms, and bullets (with special reference to self-made
      firearms), criminalistical aspects (i.e. differentiation between homicide and
      suicide, gun in the hand), morphological findings (i.e. nuchal and oral shots or
      bullet-related embolism) are introduced.

PMID- 8147701
TI  - [Significant injury of the neck including the cervical spine and soft tissue in
      suicidal strangulation].
AB  - A 46-year-old man committed suicide by jumping from a height of app. 4.5 m with a
      running noose round his neck. The neck was nearly cut through by the tightened
      ligature, so that there was only a small "bridge" of soft tissue between head and
      trunk.

PMID- 8147702
TI  - [Detection of sperm after extremely long postmortem interval (5-6 weeks)].

PMID- 8147703
TI  - [Airborne fungi during the last ten years in Sagamihara].
AB  - Airborne fungi have been surveyed every week during the 10 years from 1983 to
      1992 in Sagamihara. This is a follow up of a 1970 and a 1980 survey at the same
      sampling station (19.5 m above the ground), using the same gravity potato
      dextrose agar plate. There were two peak seasons during tsuyu (rainy season;
      June) and autumn (September to October). The most predominant fungi found, except
      for yeasts and non-sporulated fungi, were Cladosporium (2 seasons) and Alternaria
      (more frequently in tsuyu). These were followed by Epicoccum (tsuyu),
      Aureobasidium, Curvularia (summer), Ulocladium (autumn), Penicillium, Arthrinium,
      Nigrospora (summer), Fusarium, Trichoderma, Pestalotia in decreasing order of
      their total frequency throughout the 10 years. The most common fungi found during
      the most years were different from those found during 1970, particularly in the
      frequency of Aspergillus and Penicillium, but similar to those during 1980 in
      Sagamihara as well as in most areas of Japan.

PMID- 8147704
TI  - [The evaluation of hyposensitization with house dust in patients with nasal
      allergy to house dust-mite].
AB  - We evaluated the clinical and pathophysiological efficacy of hyposensitization
      with house dust extracts to perennial nasal allergy. Fifty-one patients with
      allergic perennial rhinitis completed 5 months to 15 years with a mean of 2.4
      years course of hyposensitization treatment with house dust extracts, and
      analyzed clinical symptoms, nasal provocation testing, nasal hypersensitivity to
      histamine, mast cells and eosinophils in nasal scraping, specific IgG and IgG4
      antibody in serum, and blood eosinophils and basophils in relation to therapeutic
      duration. The improvement in nasal symptoms was found in 74.1% in adults and
      66.7% in child and the continuation of hyposensitization with house dust extracts
      for a half to one year showed significant improvement of clinical symptoms. In
      objective examination, nasal provocation testing, nasal hypersensitivity to
      histamine, the number of mast cells and eosinophils in nasal scraping, and blood
      basophils showed significant improvement at 6 to 12 months the same as clinical
      symptoms. These findings suggest that the continuation of hyposensitization with
      house dust extracts is recommendable as a basic treatment against perennial nasal
      allergy.

PMID- 8147705
TI  - [Does clinical stage have any influence on the results of provocation tests in
      allergic children? I. The best clinical stage for food provocation tests].
AB  - To investigate the best clinical stage for food provocation tests, twenty
      allergic patients who had early allergic reactions induced by any kind of food
      were tested. The patients were classified into two groups. Group I; open-food
      challenge tests were performed on eleven patients within 48 hours of admission.
      Group II; the tests were performed on nine patients seven or more days after
      admission. In these food provocation tests, there were nine positive results in
      Group II (p < 0.05). The percentage of eosinophils in the blood was higher in
      cases of positive provocation than in cases of negative provocation (p < 0.05).
      Moreover the percentage of eosinophils decreased after admission day by day in
      the provocation-negative patients of Group II, but there was no change in the
      provocation-positive patients. These results suggest that individual sensitivity
      to food decreased after admission. Therefore, in order to assess the actual
      sensitivity of allergic children it is necessary that food provocation tests be
      performed within two days of admission or before admission.

PMID- 8147706
TI  - Blood levels of leukotrienes (LTC4, D4, E4, B4) in asthmatic patients during
      attack and remission.
AB  - To assess the contribution of the leukotrienes, LTC4, D4, E4 and B4 during
      bronchial asthma attacks, simultaneous determination was made of their levels in
      venous blood. 25 patients with bronchial asthma (15 atopic types, 10 non-atopic
      types) participated in this study and 4 normal controls were used. Samples were
      obtained using heparinized syringe from the patients before treatment. A
      radioimmunoassay was conducted to measure LTs after purification with a Sep-pak
      column and separation by HPLC. In normal subjects, the levels were less than the
      minimal detectable amounts. LTC4, D4, E4 and B4 during asthmatic attacks were 100
      +/- 179, 88 +/- 116, 479 +/- 291, and 55 +/- 73 (Mean +/- SD) pg/ml respectively
      (n = 27). Peptide LTs in remission were below minimal detectable levels. LTD4 in
      patients with moderate attacks was significantly (p < 0.05) higher than in those
      with mild attacks. Peptide LTs in moderate attack exceeded those in mild attacks,
      although not to a statistically significant degree. No significant differences in
      LT during attacks could be detected in atopic or non-atopic type patients. LTs
      would thus appear importantly involved in asthmatic attacks in atopic and non
      atopic type patients, although other chemical mediators may give rise to airway
      inflammation.

PMID- 8147707
TI  - Fatty acid compositions of plasma lipids in atopic dermatitis/asthma patients.
AB  - The proportions of linoleic acid in total plasma lipids and phospholipids were
      significantly greater and those of oleic acid were lower in pre-puberal and
      puberal atopic patients as compared with age-matched healthy controls. The n-3/n
      6 fatty acid ratio of the triacylglycerol fraction was also lower in atopic
      patients. However, no significant decreases in the proportions of dihomo-gamma
      linolenic acid and arachidonic acid were observed in plasma lipids of atopic
      patients, suggesting that delta 6-desaturase activity is not impaired in atopic
      patients. We provide an explanation for the beneficial effects of raising the n
      3/n-6 ratio of dietary oils in the context of suppressing allergic hyper
      reactivity in humans.

PMID- 8147708
TI  - IgG-mediated anaphylactic contraction and 86Rb efflux from guinea pig tracheal
      smooth muscle.
AB  - Tracheal muscle strips isolated from guinea pigs passively sensitized with anti
      egg albumin rabbit IgG were loaded with 86Rb as a K+ marker. The 86Rb efflux from
      the muscle tissue was measured after antigen exposure and the K(+)-channel
      subtypes involved in anaphylactic contraction were identified. The net 86Rb
      efflux was increased during antigen challenge. This increase was inhibited in
      Ca(2+)-free medium or in the medium of 40 mM of KCl, but not by 10 microM of
      glibenclamide or 20 mM of KCl. Decreased membrane potential and generation of
      action potentials were also observed during the anaphylactic contraction. As a
      comparison for antigen-induced 86Rb efflux changes, experiments using high
      concentrations of KCl were also performed. 86Rb efflux was increased depending on
      the KCl concentration. This increase was inhibited in Ca(2+)-free medium but not
      by 10 microM of glibenclamide. These results suggest that the K(+)-channel
      opening during IgG-mediated anaphylactic contraction was dependent on a decreased
      membrane potential due to 20-40 mM KCl. The subtype of the K(+)-channel involved
      is voltage-dependent K(+)-channel (Kv-channel), and Ca(2+)-activated K(+)-channel
      (KCa-channel) may also be involved in the 86Rb efflux change. The ATP-sensitive
      K(+)-channel (KATP-channel) was not involved in K(+)-channel opening during
      anaphylactic contraction.

PMID- 8147709
TI  - [Chromogranin A like immunoreactivity in respiratory tissues of ovalbumin
      sensitized guinea pigs].
AB  - Chromogranin A like immunoreactivity (CGA-IR) was measured by a specific
      radioimmunoassay using N-terminal specific antiserum R-0763 in respiratory
      tissues of guinea pigs. All guinea pig were actively immunized by recurrent
      Ovalbumin (OA)-inhalation and divided into two groups; one was challenged by OA,
      and the other inhaled saline as a control. These groups were studied for
      respiratory resistance and sacrificed for measurement of CGA-IR concentrations in
      the trachea, major bronchus and lower lung. In the control group, CGA-IR level
      was 0.4-2 pmol/g wet weight of tissue, and its distribution order was lower lung
      > trachea > major bronchus. In the OA-challenged group, provocation clearly
      induced significant elevation of CGA-IR in the trachea and main bronchus
      coinciding with elevation of respiratory resistance. In the lower lung, on the
      other hand, the increase in CGA-IR was not significant. These results suggest
      that experimental immediate asthmatic response (IAR) possibly acts as a stressor
      to the sympathetic nervous systems in guinea pig air-ways.

PMID- 8147710
TI  - [Modulation of cholinergic neurotransmission by Ca(2+)-activated K channel and
      Na(+)-K(+)-ATPase in canine airway smooth muscle].
AB  - Stimulation of Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may play an
      important role in the relaxant responses of airway smooth muscle to certain
      bronchodilators. To elucidate whether cholinergic neuroeffector transmission can
      be modulated by Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase, we studied
      canine airway smooth muscle under isometric conditions in vitro. Addition of
      charybdotoxin (ChTx, 10(-7) M) did not alter the contractile responses to
      acetylcholine (ACh) but augmented electrical field stimulation (FES)-induced
      contractions at 1-10 Hz (p < 0.01), whereas apamin and glibenclamide were without
      effect. This effect was dose-dependent, with the maximal increase being 36.8 +/-
      5.3% (p < 0.001). Ouabain at a concentration insufficient to alter the resting
      tension (10(-7) M) increased contractions induced by both EFS and ACh. The
      magnitude of the increase in contractile responses to EFS was similar to those to
      ACh at ouabain concentration of up to 3 x 10(-7) M, but the former was
      significantly greater at 10(-6) M ouabain (p < 0.05). These results suggest that
      each Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may a modulatory role in
      the cholinergic neurotransmission by inhibiting the exocytotic ACh release from
      the vagal nerve terminals.

PMID- 8147711
TI  - [The evaluation of hyposensitization with sugi pollen extracts in patients with
      nasal allergy to Japanese sugi pollen].
AB  - We evaluated the clinical and pathophysiological efficacy of hyposensitization
      with Japanese sugi pollen extracts to sugi pollinosis. Twenty patients with
      Japanese cedar pollinosis received hyposensitization with Japanese cedar pollen
      extracts for one to 15 years with a mean of 9.5 years were compared with 18
      patients without hyposensitization. The improvement of nasal symptoms was not
      found in patients with hyposensitization of sugi pollen extracts compared with
      patients with non-hyposensitization, but the number of mast cells in nasal
      scraping, nasal hypersensitivity to histamine, and specific sugi IgG4 antibody in
      serum was improved significantly compared with non-hyposensitization group. These
      findings suggest that the continuation of hyposensitization with sugi pollen
      extracts is recommendable as a basic treatment against seasonal nasal allergy.

PMID- 8147712
TI  - [Measurement of specific IgE antibody to false cypress (Chamaecyparis obtusa,
      Hinoki) pollens using Shionoria specific IgE].
AB  - A basic and clinical study was carried out to evaluate the usefulness of the
      Shionoria Specific IgE (SIST) kit for false cypress allergen. The test materials
      were sera from 152 patients who visited our clinic with symptoms of nasal allergy
      during the period when Japanese cedar and false cypress pollens are prevalent in
      the air. The standard curve drawn on the standard serum, which was part of the
      test kit, was linear. Dilution, inhibition and absorption tests were all
      satisfactory. Reproducibility studies, different-day, and inter-performers, were
      all excellent. Nonallergic sera and umbilical cord sera showed less reactivity
      than the reference serum which is classified as class 0. The sensitivity of the
      SIST kit for False cypress was 89.9%; specificity 86.3%, and concordance rate
      88.2%. The SIST test results for the sera well correlated with the results given
      by skin tests. These results are good evidence of the excellence of this kit. It
      was of interest that in the inhibition test, some false cypress positive sera
      were blocked with Japanese cedar extract as well as with false cypress extract,
      while other false cypress positive sera were blocked only with false cypress
      extract. Similar results were obtained in the absorption test. This suggests that
      the antibodies of some patients recognize a portion of the false cypress allergen
      which is common to a particular portion of the Japanese cedar allergen.

PMID- 8147714
TI  - [Special cloth futon-cover (Miroguard) as a protection against house dust mite
      exposure].
AB  - We studied the efficacy of a special cloth encasing (Microguard) in protecting
      against house dust mite exposure. We vaccumed dust from right or left half
      surface of a shiki-futon (Japanese style mattress). Then we encased the shiki
      futon by a new special encasing, vaccumed dust from the other part of the shiki
      futon and got a pair of dust samples. We had done the same of the same shiki
      futon by a used special encasing (used for one and half years) for about 2 weeks
      later. We prepared 7 shiki-futons and collected 14 pair dust samples. We weighed
      the dust and measured the mite allergens with a monoclonal antibody to
      Dermatophagoides pteronissynius and Dermatophagoides farinae. The dust level was
      1.0% of the control (no encasing) in the new encasing group and 2.0% of the
      control in the used encasing group. The Der I concentration was 2.5 micrograms/(g
      dust) in the new encasing group and 3.2 micrograms/(g dust) in the used encasing
      group. The Der II concentration was 1.6 micrograms/(g dust). The total amount of
      Der I was 0.1% of the control in the new encasing group and 0.5% of the control
      in the used encasing group. The total amount of Der II was 0.2% of the control in
      the new encasing group and 0.7% of the control in the used encasing group. We
      compared Der p and Der f levels in the dust samples which we assayed and found no
      significant differences either in Der I or in Der II allergen. We concluded that
      Microguard was a useful tool to avoid mite allergen exposure by reducing not only
      the concentration of mite allergens but also the amount of dust.

PMID- 8147713
TI  - [Decreased theophylline clearance in children with acute asthma with concurrent
      febrile respiratory infection].
AB  - Elevated serum levels of theophylline, a first-line anti-asthma drug, are
      sometimes associated with febrile respiratory infection (FRI). Although it seems
      to be wellknown, conflicting reports still appear in journals. We studied
      retrospectively theophylline clearance (th-cl) in 74 episodes of acute asthma (44
      with and 30 without FRI, in patients aged 12-mos.-13-yrs.) and tried to reveal
      the effect of fever or pathogens on th-cl. Th-cl was estimated by a single sample
      technique during intravenous drip infusion of aminophylline. The results were as
      follows: 1) Forty four episodes with FRI included 20 viral, 10 bacterial and 2
      Mycoplasma pneumoniae infections (Table 2). 2) Th-cl in 44 episodes with FRI was
      significantly lower than in 30 without FRI (p < 0.001). 3) Decreased tendency of
      th-cl in episodes with viral infection was observed, but statistically it was not
      significant (p < 0.1). However, the differences of th-cl among 9 pair-cases with
      and without viral infection were quite clear (p < 0.01). 4) Th-cl in episodes
      with 10 bacterial and 2 Mycoplasma infections was reduced significantly (p <
      0.01). 5) There was no difference in th-cl between episodes with viral, and
      bacterial or Mycoplasma infections (p < 0.1). As a result, it is suggested that
      fever, regardless of its origin, may decrease th-cl in acute asthma with FRI.

PMID- 8147715
TI  - [Fundamental studies on the measurement of urinary leukotriene E4].
AB  - We undertook fundamental studies on the measurement of urinary leukotriene E4, a
      stable end-product of peptidoleukotrienes, and obtained the following results. 1)
      After addition of 3H-LTE4 to 2 ml of urine, LTE4 was extracted with a commercial
      C18 mini-column, and purified by high performance liquid chromatography and then
      LTE4 in the elute was measured with an enzyme immunoassay kit. 2) As total
      recovery of LTE4 was 35.3 +/- 0.9% (n = 76), the amount of LTE4 was calculated
      after correction of the recovery with 3H-LTE4. 3) Before extraction of LTE4 by
      C18 column, the column was washed by ethyl acetate to remove interfering
      substances. This procedure greatly facilitated the following high performance
      liquid chromatographic analysis. 4) The basal levels of urinary LTE4 of seven
      aspirin-sensitive asthmatics were elevated as compared with five asthmatics
      without aspirin sensitivity (358.9 +/- 114.0 versus 77.9 +/- 47.3 pg/mg.cr; p <
      0.05). 5) In two asthmatic patients, improvement of their symptoms was
      accompanied with decrease in the LTE4 level in urine. This method enabled us to
      measure LTE4 concentrations in a small volume of urine (2 ml), and would be
      useful for evaluating the pathogenesis of bronchial asthma.

PMID- 8147716
TI  - [Measurement of total IgE in sera from normal subjects and allergic patients by
      chemiluminescent immunoassay].
AB  - We measured the total IgE in sera from normal and allergic subjects by using the
      "Magic Lite Total IgE High Sensitivity" chemiluminescent immunoassay kit. The
      accuracy precision and correlation with RIST of this kit were sufficient to use
      it for clinical diagnosis. The analytical sensitivity was 0.075 IU/ml, and this
      kit was sensitive enough to measure total IgE in cord blood. The mean and SD of
      total IgE measured in the sera of 115 cases of the normal subjects was 72.3 +/-
      83.7 IU/ml, and the 95% confidence level of those values was 280 IU/ml. Thus the
      cutoff value of the total IgE appeared to be 250-300 IU/ml. The total IgE values
      measured in the sera of the bronchial asthma group and the allergic rhinitis
      group were significantly higher than those of the normal subjects. RAST scores to
      house dust and house dust mites correlated with the total IgE values in the sera.
      The values of total IgE measured in the cord blood group ranged from 0.075 IU/ml
      (limit of the sensitivity) to 10.09 IU/ml, and the geometric mean was 0.295
      IU/ml. Ten % of the cord blood samples showed IgE values of more than 1 IU/ml. As
      a method of measuring total IgE in cord blood, this kit would appear, from our
      results, to be useful for the detection of atopic factors in the early stages of
      life.

PMID- 8147717
TI  - An antiallergic drug, pemirolast potassium, inhibits inositol 1,4,5-trisphosphate
      production and Ca2+ mobilization in antigen-stimulated rat basophilic leukemia
      (RBL-2H3) cells.
AB  - An antiallergic drug, pemirolast potassium (TBX) at concentrations between 0.01
      and 10 micrograms/ml inhibited antigen (Ag)-stimulated degranulation in RBL-2H3
      cells, which have the properties of mucosal mast cells. At the same
      concentrations, the drug suppressed both the formation of inositol 1,4,5
      trisphosphate and the mobilization of Ca2+, indicating the prevention of
      phospholipase C activation. The production of 1,2-diacylglycerol and phosphatidic
      acid, which was mainly due to phosphatidylcholine hydrolysis, was also
      suppressed. Moreover, TBX reduced Ag-induced liberation of arachidonic acid, a
      precursor of eicosanoids, implying the inhibition of phospholipase A2. These data
      suggest that TBX inhibits the activation of phospholipase C, leading to decreased
      formation of the signal transducing molecules necessary for cell activation.

PMID- 8147718
TI  - [Bronchial asthma: bronchial spasm and remodeling].

PMID- 8147719
TI  - [Protracted (lasting) presence of Japanese cedar pollen allergen (Cry j I) in
      house dust].
AB  - We investigated the relationship between the amounts of Cry j I in house dust and
      airborne Cryptomeria japonica pollen in the same location. Cry j I was still
      detected in house dust collected two weeks after airborne C. japonica pollen had
      disappeared. Disappearance of Cry j I in house dust coincided with the
      disappearance of symptoms in the C. japonica pollinosis patients who lived in the
      same area. Airborne Cupressaceae pollen appeared during the latter half of the C.
      japonica pollen season. Disappearance of Cupressaceae pollen did not coincided
      with the disappearance of the symptoms in C. japonica pollinosis patients.
      Therefore, some symptoms of C. japonica pollinosis patients after C. japonica
      pollen disappeared from the air may be caused by pollen which had attached to
      clothes and been brought indoors.

PMID- 8147720
TI  - [Coronary transluminal angioplasty. The surgeon's point of view].

PMID- 8147721
TI  - [Thoracic pain in children].

PMID- 8147722
TI  - [Doppler echocardiography evaluation of the hemodynamic performance of the
      Lillehei-Kaster and Medtronic Hall valves in aortic position].
AB  - PURPOSE: To establish the range of normal values by Doppler echocardiography of
      the parameters inherent to the hemodynamic performance of the Lillehei-Kaster
      (LK) and Medtronic Hall (MH) prosthetic valves (V), in the 23 mm (LKV-16, MHV-23)
      and 25 mm (LKV-18, MHV-25) outer diameter valves, in the aortic position.
      METHODS: Doppler echocardiography was performed in 32 asymptomatic patients, with
      normally functioning prosthetic aortic valves (8 of each type). RESULTS: The peak
      velocity of aortic jet was 3.13 +/- 0.46 m/sec for the LKV-16, 2.76 +/- 0.31
      m/sec for the MHV-23, 2.82 +/- 0.48 m/sec for the LKV-18 and 2.43 +/- 0.36 m/sec
      for the MHV-25. The maximal pressure gradient was 39.84 +/- 12.05 mmHg for the
      LKV-16, 30.70 +/- 6.80 mmHg for the MHV-23, 32.60 +/- 10.75 mmHg for the LKV-18
      and 24.11 +/- 6.70 mmHg for the MHV-25. The mean pressure gradient was 24.25 +/-
      7.09 mmHg for the LKV-16, 18.50 +/- 4.41 mmHg for the MHV-23, 18.21 +/- 6.95 mmHg
      for the LKV-18 and 13.57 +/- 4.17 mmHg for the MHV-25. The valve effective
      orifice area, considering the left ventricle outflow area determined by two
      dimensional echocardiography in the continuity equation, was 0.62 +/- 0.13 cm2
      for the LKV-16, 1.05 +/- 0.21 cm2 for the MHV-23, 0.98 +/- 0.22 cm2 for the LKV
      18 and 1.36 +/- 0.36 cm2 for the MHV-25. Considering the left ventricle outflow
      area equivalent to the valve sewing ring area, the valve effective orifice area
      was 1.40 +/- 0.23 cm2 for the LKV-16, 1.65 +/- 0.19 cm2 for the MHV-23, 1.91 +/-
      0.43 cm2 for the LKV-18 and 2.37 +/- 0.56 cm2 for the MHV-25. The Doppler
      velocity index was 0.34 +/- 0.05 for the LKV-16, 0.40 +/- 0.04 for the MHV-23,
      0.39 +/- 0.09 for the LKV-18 and 0.49 +/- 0.11 for the MHV-25. CONCLUSION:
      Significant hemodynamic performance superiority of the MHV over the LKV was
      registered, indicating that the small LKV (LKV-16 or smaller) should be avoided.

PMID- 8147723
TI  - [Delayed follow-up after aortic coarctation correction. Subsequent surgical
      reoperation].
AB  - PURPOSE: To determine the frequency and main features of subsequent
      cardiovascular surgery in patients operated on for coarctation of the thoracic
      aorta. METHODS: One hundred and five patients operated on for coarctation of the
      aorta with a mean follow-up period of 14 years had their notes analysed. The
      patients were divided in 4 groups according to age at correction of the
      coarctation. The incidence of recoarctation repair and other cardiovascular
      operations were noted. RESULTS: Surgical morbidity was important: 33%.
      Recoarctation occurred in 14% of the cases, mainly in those who had the
      coarctation resected during the first year of life. Operation for other
      cardiovascular defects was necessary in 24.5% of the cases. Among these,
      correction of left-to-right shunts was done in 50% of the patients who had the
      coarctation resected in the first year of life. Relief of aortic stenosis was the
      most frequent procedure (73%), tends to be more frequent the other is the patient
      at coarctation repair and more than one procedure may be necessary in some cases.
      CONCLUSION: Reoperation is frequent in the long term of patients operated on for
      coarctation of the aorta. The elective coarctation should be repaired after the
      first year of life hoping to avoid recoarctation. Routine follow-up is advisable
      for all patients aiming to detect residual left-to-right shunts and left
      ventricular outflow tract obstruction. Family counseling regarding prognosis
      after coarctation resection is recommended.

PMID- 8147724
TI  - [Blood pressure in a Xavante tribe. Comparison after 15 years].
AB  - PURPOSE: To evaluate arterial blood pressure (BP), variations that occur with
      age, influence of new habits, in indians of a Xavante tribe, located in the state
      of Mato Grosso, Brazil. METHODS: The evaluation procedures took place in 9/75 and
      10/90. Fifty Xavante were examined in 1975. Thirty-five of them were men and 15
      women. The mean age of the men was 45 and of the women, 31. In 1990, only 46 of
      those indians were re-examined (two were not located and two had already died of
      cancer and pneumonia), and evaluated with regard to arterial BP, food ingestion,
      physical activities, obesity, tobacco, alcoholic beverage consumption and social
      organization. RESULTS: In both occasions we did not find individuals with
      hypertension. The highest BP observed was of 140 x 90 in a 70-year-old indian.
      His result is consistent with what had been noted in 1975. Among the women, the
      highest level was of 130 x 60 in a 55-year-old female indian. The women
      maintained a lower level of BP as compared to the men of any age group. The
      average blood pressure showed a discrete increase going from 79.2 to 83.8 mmHg in
      the men and from 75.7 to 77.0 mmHg in the women. In this tribe we observed the
      habit of smoking in 30% of the individuals. Alcoholic beverage consumption is
      rare, physical activities remained constant and obesity is absent. As for the
      eating habits, with the decrease of hunting grounds, the indians acquired a more
      rural behavior with regular use of rice and beans. Salt is practically not added
      to the food. Competitiveness is not an acquired trait to that culture.
      CONCLUSION: In "isolated" populations that maintain their cultural traits and
      basic life styles, the occurrence of arterial hypertension is very rare and the
      increase in BP with age is modest and significant only for systolic.

PMID- 8147725
TI  - [The endocrine heart. The discovery of the atrial natriuretic peptide].

PMID- 8147727
TI  - [Fatal myocardial infarction in a young patient due to coronary arteritis].
AB  - A 34 year-old male patient suffered an acute anterior wall infarction at age 32.
      Myocardial ischemia was demonstrated later by stress testing and thallium
      myocardial scintigraphy. Coronary arteriography revealed a proximal 90%
      obstruction of the left anterior descending artery. The patient was submitted to
      percutaneous transluminal coronary angioplasty. The procedure was unsuccessful as
      the catheter could not progress through the obstruction. On follow-up, there was
      less than ideal adherence to medical treatment and the patient complained of
      occasional atypical non-effort related chest pain. Two years later the patient
      suffered a large fatal myocardial infarction. Necropsy disclosed that the cause
      of myocardial infarction was severe coronary arteritis of left circumflex artery
      with giant cell granulomas.

PMID- 8147726
TI  - [Streptokinase in severe pulmonary thromboembolism].
AB  - Severe pulmonary embolism (PE) was treated with streptokinase in four patients,
      three men and one woman, age 38 to 72 (mean = 53 +/- 14) years. Before the
      thrombolytic therapy, all patients had pulmonary angiogram and hemodynamic
      parameters analyzed. The drug was infused through the distal lumen of the Swan
      Ganz catheter at the pulmonary artery trunk. The initial dosage was 250,000 units
      "in bolus" and 100,000 units in 24 to 72 hours. The time interval between the
      symptoms and treatment had ranged from 2 hours to 5 days. The results are
      analyzed as follow: reduction on right atrial pressure, mean pulmonary pressure,
      pulmonary vascular resistance, an increase in the stroke volume and cardiac
      output. In two cases we observed total lysis, in one partial lysis and one
      patient died from severe form of PE and late infusion of SK. Reinfusion of the
      drug was necessary in one patient that had PE recurrence with reliable final
      result. Finally, no one had severe bleeding despite the use of the intrapulmonary
      catheter.

PMID- 8147728
TI  - [Thrombolytic treatment in pulmonary thromboembolism in the postoperative period
      following heart surgery complicated by ischemic cerebrovascular attack].
AB  - A 69 years old man with pulmonary embolism early after coronary bypass surgery
      complicated by ischemic stroke received thrombolytic therapy. Reperfusion of the
      pulmonary artery was achieved. Conversion of the ischemic stroke to hemorrhagic
      infarction was observed at the CT-Scan without neurological impairment.

PMID- 8147729
TI  - [Surgical treatment of total anomalous drainage of pulmonary veins into the right
      superior vena cava].
AB  - This report describes a 2-month-old boy with diagnosis of total anomalous
      pulmonary venous obstruction and marked hypertension established by cross
      sectioned echocardiography and catheterization with angiography. Successful
      surgical correction was performed with profound hypothermia and circulatory
      arrest. The risk factors and the high operative mortality associated with this
      type of anomaly are analyzed.

PMID- 8147730
TI  - [Intermittent ventricular pre-excitation in the presence of total
      atrioventricular block].
AB  - An 8 year old child suffering from asthenia and complete atrioventricular block,
      probably congenital. During the tread-mill test there was a sudden
      electrocardiogram change to a ventricular preexcitation pattern. Besides this
      rare association, we emphasize the importance of the autonomic balance over the
      accessory pathway's electrophysiological properties. The appearance of a latent
      accessory pathway might be a substitutive mechanism to counterbalance the serious
      impairment of physiologic atrioventricular conduction.

PMID- 8147732
TI  - [Synchronous and metachronous tumors of the colon and rectum. Value of the early
      diagnosis].

PMID- 8147731
TI  - [A Brazilian multicenter study to evaluate the clinical effectiveness and
      tolerance of isradipine SRO using ambulatory monitoring of arterial pressure in
      the treatment of mild and moderate arterial hypertension].
AB  - PURPOSE: To evaluate clinical efficacy and tolerability of isradipine SRO
      (I.SRO), 5 mg O.D. in essential hypertensives. METHODS: Eighty-three of 87
      selected outpatients with a mean age of 51.3 years (ranging from 25 to 65), 33
      male, 48 white, 29 black and others of different races, who had clinical supine
      and orthostatic diastolic blood pressure (DBP) > or = 95 mmHg and < or = 115 mmHg
      underwent the study. After a three-week wash-out period, patients received I.SRO
      5 mg O.D. at 8:00 am for a six-week period (phase I). After this phase, patients
      received I.SRO 5 mg O.D. at 8:00 pm for a six-week period (phase II). The
      patients had a follow-up with an interval of three weeks and the ambulatorial
      blood pressure monitoring (ABPM) for 24 hours was performed with a SpaceLabs
      90207 or Del Mar Avionics devices after the wash-out period and at the end of
      phases I and II. Measurements were performed at 15-min intervals during the day
      (6 am to 10 pm) and at 30-min intervals during the night (10 pm to 6 am).
      RESULTS: a) Heart rate did not show significant changes during the treatment
      period (phases I and II) when compared with the wash-out period; b) causal blood
      pressure: at the end of both treatment periods (phases I and II) there were
      statistically significant decreases (p < 0.001) in supine SBP and DBP compared
      with wash-out values. The mean SBP decreased from 161.6 +/- 14 to 144.3 +/- 13
      mmHg (phase I) and to 141.8 +/- 13 mmHg (phase II). The mean DBP decreased from
      103.4 +/- 6 to 91.2 +/- 7 (phase I) and to 89.1 +/- 8 (phase II); c) ABPM: the
      mean systolic 24-h ambulatory blood pressure was significantly reduced (p <
      0.001) from 148.8 +/- 17 to 137.2 +/- 15 mmHg (phase I) and to 133.4 +/- 13 mmHg
      (phase II). The mean diastolic 24-h ambulatory blood pressure was significantly
      decreased (p < 0.001) from 94.3 +/- 9 to 87.0 +/- 9 (phase I) and to 85.8 +/- 8
      mmHg (phase II). The mean daytime and nighttime, systolic and diastolic 24-h
      ambulatory blood pressure were: wash-out--152.3 +/- 17, 140.2 +/- 21, 97.4 +/- 9,
      86.8 +/- 13; phase I--139.9 +/- 15, 130.0 +/- 17, 89.3 +/- 9, 81.3 +/- 10; phase
      II--136.7 +/- 13, 125.3 +/- 15, 88.5 +/- 8, 79.1 +/- 10, respectively. Blood
      pressure load (percentage of systolic blood pressure values > 140 mmHg or of
      diastolic blood pressure values > 90 mmHg) was significantly reduced from
      62.2/62% (SBP/DBP), on the was-out, to 37.9/39.9% (SBP/DBP) on phase I and to
      32.3/34.3% (SBP/DBP) on phase II; d) side effects: most frequently related were
      palpitations (2.3%), headache (1.1%), flush (1%) and ankle oedema (1%). They were
      in general, mild-to-moderate and disappeared after the first 3 weeks of
      treatment. Only two patients were withdrawn because of headache (one of them with
      previous diagnosis of migraine). CONCLUSION: I.SRO, given by oral route, in the
      dosage of 5 mg O.D. as monotherapy, was effective and well tolerated, promoted
      significant reduction on 24-h ambulatory blood pressure attenuating the early
      morning rise and did not interfere with the circadian rhythm of blood pressure.
      No significant differences were detected in the BP lowering effect when I.SRO was
      given during the morning or evening. These results may indicate that the drug is
      as suitable as one of the first choice for treating mild and moderate
      hypertensive patients.

PMID- 8147733
TI  - [Synchronous and metachronous tumors of the colon and rectum].
AB  - Three hundred and seventy-two patients with colorectal tumours treated by
      curative resection between January 1982 and January 1992 were reviewed in order
      to determine the role of colonoscopy and the outcome of patients with multiple
      tumours. Thirty (8.1%) of them with a mean age of 57 (35-79) years (20 males, 10
      females) had synchronous (19 cases) or metachronous (11 cases) lesions. Rectum
      and sigmoid colon were the most frequent site of multiple lesions, accounting for
      73% of all lesions. Accurate pre-operative diagnosis was performed in 14 of the
      19 patients with synchronous lesions, and in the remaining 5 cases failure to
      perform an intra-operative colonoscopy was the cause of missing the lesions.
      Three of them had over-looked lesions on the previous barium enema. Synchronous
      lesions has the tendency to be less invasive as compared to metachronous ones.
      Five-year survival rates (Kaplan-Meier method) were 45% and 58% for patients with
      multiple and single lesions respectively (not significant). For patients with
      colorectal carcinoma a thorough examination of the whole colon by intra-operative
      colonoscopy should be accomplished in order to rule out the possibility of
      associated lesions as well as to decrease the incidence of "early" metachronous
      lesions.

PMID- 8147734
TI  - Small cell carcinoma of the esophagus. Clinicopathological and
      immunohistochemical findings in four cases.
AB  - Small cell carcinoma of the esophagus is an uncommon neoplasm. The authors report
      the clinicopathologic and immunohistochemical findings in four cases. Dysphagia
      was the most frequent symptom at presentation. Only one patient was treated by
      surgery; the other did not receive any treatment. Histologically, three were oat
      cell type tumors with areas of intermediate cell type. Combined cell type was not
      present. Immunohistochemistry demonstrated positivity for neuron-specific enolase
      and for chromogranin in all four cases. One case was a double primary carcinoma,
      a squamous cell carcinoma and a small cell carcinoma.

PMID- 8147735
TI  - Achalasia occurring years after acute poliomyelitis.
AB  - We present a case of a 19 year old female patient with dysphagia for 4 months.
      Radiologic, endoscopy and manometric examinations were compatible with the
      diagnosis of idiopathic achalasia. Clinical, epidemiologic and serologic
      investigation was negative for Chagas' disease. When she was three years old she
      had acute poliomyelitis that left muscular atrophy in her left leg. It is
      possible that lower esophageal sphincter achalasia was the consequence of lesion
      in the dorsal motor nucleus of the vagus nerve caused by poliomyelitis. The
      association between poliomyelitis and achalasia supports the infective hypothesis
      as the cause of achalasia.

PMID- 8147736
TI  - Gastric duplication presenting rectal bleeding. A clinical case supporting
      McLedtchie's theory.
AB  - This is a case of a 5-month-old girl with massive rectal bleeding caused by a
      gastric duplication. Cyst heterotopic pancreas and pancreatic duplication, an
      association not previously reported were present. The peculiar clinical
      presentation was due to cyst perforation that had subsequently eroded the
      transverse colon. Coexistent gastric containing heterotopic pancreas and
      pancreatic duplications were probably produced as traction diverticular by an
      embryonic entoectodermal adhesions.

PMID- 8147737
TI  - [Gastrointestinal vascular malformation].
AB  - Dieulafoy's disease, described in 1898, has been considered a rarity.
      Morphologically is represented by single, large and tortuous artery located in
      the gastric submucosa and overlying by submucosal defect that is responsible for
      severe digestive bleeding. We report two cases of this gastrointestinal vascular
      malformation: one in the stomach and the other in the jejunum. We believe that
      better knowledge of this lesion and more reports about it are important to
      decrease the mortality rate in those cases.

PMID- 8147738
TI  - [Simple and rapid technique of intubation for collection of jejunal secretions].
AB  - This study was proposed to introduce a new and fast technique of aspiration to
      obtain samples of the small bowel juice. The utilization of a guide wire placed
      within the main probe lumen provides more rigidity to the system. We compared the
      traditional technique and the new one in 40 infants. The time elapsed for
      intubation was shorter with the guide wire (mean 15.4 minutes) than with the
      traditional technique (91.0 minutes (p < 0.05). In order to make the method more
      feasible the positioning of the tube was assessed by the change in the colour of
      the intestinal fluid and by the pH measurement of the intestinal aspirate.

PMID- 8147739
TI  - [Pancreatic metastasis from renal cell carcinoma].

PMID- 8147740
TI  - The role of sleep in migraine attacks.
AB  - Migraine attacks may be precipitated by sleep deprivation or excessive sleep and
      sleep is also associated with relief of migraine attacks. In view of this
      variable relationship we studied the records of 159 consecutive outpatients of
      our Headache Unit. In 121 records there was reference to sleep involvement, in
      55% by a single form and in 45% by more than one form. When only one form was
      related, relief was most common (70%). 30% of that group of patients had the
      migraine attack precipitated by sleep, 24% by deprivation and 6% by sleep excess.
      When the effects of sleep were multiple, these effects were as expected logically
      in 65%: "in accordance" group (e.g attack precipitated by sleep deprivation and
      relieved by sleep onset. In a second group, ("conflicting") where the involvement
      was not logical, there were three different combinations of sleep involvement,
      possibly due to more than one pathophysiological mechanism.

PMID- 8147741
TI  - [Objective auditory evaluation by evoked potentials].
AB  - We have analyzed 1300 Auditory Brain-Stem Response Audiometry exams. The patients
      were distributed according to criteria related to age, clinical presentation,
      hearing impairment risk-factors and hearing thresholds. The results were divided
      into five groups of hearing thresholds: normal hearing (threshold response
      obtained up to 25 dBHL); mild hearing loss (25-50 dBHL); moderate hearing loss
      (50-70 dBHL); severe hearing loss (70-90 dBHL); and without response to acoustic
      stimuli. We have studied the risk-factors related to gestation, delivery and
      neonatal period, family history of hearing loss, hearing apparatus malformations,
      craniofacial anomalies, certain modalities of infectious diseases, hearing
      impairment associated syndromes, and the use of some kind of drugs. Cerebral
      palsy, neuropsychomotor development retardation and cases without known
      antecedents were also studied. The main results of our study show: 82.8%
      incidence of hearing impairment; the late performance of examinations to evidence
      a definite hearing loss as 54.1% of the examined patients were at ages ranging
      from one to three years old; 54.0% of total cases have not presented any language
      development; the risk-factor "Congenital Rubeola" has the expressive incidence of
      14.8% and the distribution of this value into hearing threshold ranges has shown
      an exponential increase which demonstrates a close correlation between that
      disease and hearing impairment.

PMID- 8147742
TI  - [Trends of mortality from cerebrovascular disease in the State of Sao Paulo: 1970
      to 1989].
AB  - AIM: description of proportional mortality and death rates by Stroke in adult
      population (20 years of age or older) of Sao Paulo State, Brazil. METHODS: the
      deaths were obtained from the statistical official bureau; the population data
      were based in the Federal Census (1970, 1980 and 1991); all trends whose the
      slope was significantly greater than zero had a calculation of the decline per
      year. RESULTS: proportional mortality for Stroke decreased for males (M) (
      11.40%) and increased for females (F) (+7.58%); Stroke in all cardiovascular
      diseases showed increase in both sexes, +8.65% (M) and +3.12% (F); Stroke age
      adjusted death rates declined 1.19% (M) per year and 1.76% (F) per year between
      1970 and 1989; the ages whose decline was more important were those 60-years-old
      of age or older (M) and 40-years-old or older (F); the male/female sex ratio
      increased during the observed years (22% in 1970 to 45%) due to the change in the
      50-59 age strata (36% in 1970 to 69% in 1989). CONCLUSION: the fall of the Stroke
      deaths rates could be due to increase in the detection and control of
      hypertension; other factors such as improve in death certification, decline of
      Chagasic myocarditis, new image-diagnostic tests and medical care had maybe only
      a secondary play in the decline of stroke mortality.

PMID- 8147743
TI  - HTLV-1 and myelopathy in Salvador (northeastern Brazil): a case control study.
AB  - The principal aim of the study was to determine the degree of association between
      cerebrospinal fluid (CSF) that is positive for HTLV-1 and myelopathy in Salvador,
      Brazil. From the same hospital, twenty-eight cases of myelopathy and twenty-eight
      cases showing no neurological disorder were studied using blind selection matched
      1:1 by age and sex. The twenty-eight pairs underwent HTLV-1 serology tests. In
      those with a positive result, anti-HTLV-1 antibodies were investigated in the
      CSF. The ELISA method was used, complemented by the Western-blot test. Myelopathy
      was considered associated with HTLV-1 only when the CSF was positive indicating
      neurotropism of the virus. The mean age of the cases was 44.6 +/- 15.6 years and
      the control group was 43.5 +/- 16.0 (p > 0.05). An OR of 9.0 was detected with a
      reliability interval (95%) of 1.652-48.866 and chi-square significant at the 0.02
      level. Despite a strong degree of association and considering the low level of
      precision, there is a need for analytical studies with larger samples which
      besides improving the precision will allow for greater control of the confounding
      variables.

PMID- 8147744
TI  - Arachnoid granulation affected by subarachnoid hemorrhage.
AB  - The purpose of this study was to investigate using light microscopy the
      fibrocellular components of arachnoid granulations affected by mild and severe
      subarachnoid hemorrhage. The erythrocytes were in the channels delimited by
      collagenous and elastic bundles and arachnoid cells, showing their tortuous and
      inter-communicating row from the pedicle to the fibrous capsule. The core portion
      of the pedicle and the center represented a principal route to the bulk outflow
      of cerebrospinal fluid and erythrocytes. In the severe hemorrhage, the
      fibrocellular components are disorganized, increasing the extracellular channels.
      We could see arachnoid granulations without erythrocytes, which cells showed big
      round nucleus suggesting their transformation into phagocytic cells.

PMID- 8147745
TI  - [Involvement of the nervous system in leptospirosis. I. Evaluation of neurologic
      aspects].
AB  - From January 1st up to September 30th 1990, 77 patients with leptospirosis
      confirmed by laboratory studies were admitted at the Infectious and Parasitic
      Diseases Service of the Hospital das Clinicas of the Universidade Federal de
      Pernambuco. Clinical manifestations had sudden onset with presence of fever,
      headache, chills and muscle pains. Plurisystemic involvement was observed both in
      the icteric and in the non-icteric patients. The neurological exam was abnormal
      in 70 of the patients (90.91%). Neurological findings were essentially variable.
      Though in a transitory form, they allowed the observation of the following
      clinical forms: meningoencephalitis and polyneuritis in association,
      meningoencephalitis, polyneuritis, and subarachnoid hemorrhage.

PMID- 8147746
TI  - [Involvement of the nervous system in leptospirosis. II. Cerebrospinal fluid
      evaluation].
AB  - From January 1st up to September 30th 1990, 77 patients with leptospirosis
      diagnosis confirmed by laboratory studies were admitted at the Infectious and
      Parasitic Disease Service of the Hospital das Clinicas of the Universidade
      Federal de Pernambuco. The neurological exam was abnormal in 70 of the patients
      (90.91%). The cerebrospinal fluid (CSF) examination was carried out on 67 (87%)
      of the patients; it was abnormal in 64 (95.52%) yielding hypercytosis in the
      majority of cases. There was no difference in the CSF behavior in report to the
      several neurological forms nor in relation to the icteric or non-icteric forms of
      the disease. Significant were the results for the microscopic agglutination tests
      for leptospirosis in the CSF.

PMID- 8147747
TI  - [Involvement of the nervous system in leptospirosis. III. Immunologic reactions
      in the blood and cerebrospinal fluid].
AB  - From January 1st up to September 30th 1990, 77 patients with leptospirosis were
      admitted at the Infectious and Parasitic Diseases Service of the Hospital das
      Clinicas of the Universidade Federal de Pernambuco. The majority (64) were male
      patients, and average age was 28 years old. Serovars icterohaemorrhagic and
      canicola were the most frequent. CSF examination was performed in 67 (87.0%)
      patients and it was abnormal in 64 (95.52%). Micro-agglutination test for
      leptospirosis with live antigens was performed in CSF, as well as immunological
      tests for syphilis, cysticercosis and schistosomiasis for differential diagnosis.
      Concerning the serovar identification, results of microagglutination test for
      leptospirosis in CSF were significant considering the similitude of responses
      when compared to those found for blood samples.

PMID- 8147748
TI  - [Distal myopathies: clinical, laboratory, electromyographic, histologic
      histochemical analysis of 8 cases].
AB  - Distal myopathies are uncommon diseases presenting difficulties in the
      classification by the lack of sufficient knowledge on pathogenesis. We describe
      eight cases of distal myopathies (five male and three female patients) whose
      symptoms started at the age of 10 in five and 20 in three. Symptoms started in
      the distal muscles of lower limbs, following decreased strength in the distal
      portion of upper limbs, and later on involvement of proximal muscles. Serum
      enzymes increase was slight in five, moderate in one, and important in two. EMG
      suggested primary myopathy in four, denervation in two, and was mixed type in
      another. Muscle biopsies showed features of myopathy and denervation in two
      cases, active chronic myopathy in five, and chronic myopathy in another. Four
      cases had vacuoles with positive acid phosphatase reaction and in two cases
      rimmed vacuoles were found. Six cases had increase of focal phosphatase acid in
      the muscle fibers suggesting a lissome participation in the pathogenesis of the
      disease. Two cases were classified as recessive autosomal distal myopathy
      (Welander variant), two recessive autosomal (Miyoshi type), two autosomal
      recessive with rimmed vacuole (Myzuzawa and Nonaka type), and two as miscellany
      type.

PMID- 8147749
TI  - [Desmoplastic medulloblastoma: histologic factors of prognosis].
AB  - The histological features of eight cases of desmoplastic medulloblastoma were
      investigated and compared to classic medulloblastoma. The most benign histologic
      neoplasms belong to the group of desmoplastic medulloblastoma, characterized by
      low necrosis, low mitosis and light nuclear pleomorphism.

PMID- 8147750
TI  - Involuntary movements and AIDS: report of seven cases and review of the
      literature.
AB  - We studied 1086 AIDS patients in the last six years. Of these 389 (35.82%) had
      neurological manifestation and 7 (1.8%) male patients had abnormal involuntary
      movements (parkinsonism in 3, hemichorea-hemiballism in 2, spinal myoclonus in 1
      and rubral tremor in another). All patients were men, 5 white and 2 black. Four
      were homosexual, 2 drug-users and 1 bisexual. The mean age was 33.14 years. The
      time between AIDS diagnosis and the onset of movement disorders was 23.8 months
      in 5 patients and in 2 it was the first symptom. The parkinsonian patients did
      not show any opportunistic infection in connection with the neurological symptoms
      but in the remaining four cases this relationship was suggested. The data showed
      that not only the opportunistic infection but also the AIDS virus may play an
      important role on the development of involuntary movements.

PMID- 8147751
TI  - Spinal myoclonus: report of four cases.
AB  - Four cases of spinal myoclonus are described, three males and one female. The
      mean age was 51 years (28-75 years). The mean time between the onset of the
      myelopathy and the myoclonic jerks was 4.3 months (1-8 months). The involuntary
      movements were determined by trauma, Devic's disease, tuberculous myelopathy and
      tumor. Three patients had spastic paraplegia with bilateral myoclonus more
      evident on the right side. The fourth patient had a flaccid paraplegia with
      symmetrical jerks. The data suggest that different processes (trauma,
      demyelinating, infection and tumor) affecting the spinal cord may cause the same
      type of involuntary movements.

PMID- 8147752
TI  - [Congenital hemiparesis: complementary neuropsychological evaluation with
      computer].
AB  - We present the neuropsychological assessment with computer aid of six cerebral
      palsy children. Three children had right hemiparesis and three, left hemiparesis.
      The tomographic examination showed parietal cavities (porencephalic cyst in 4
      children, ischemic injury in 1 case and subarachnoid cyst in 1 case). We have
      proposed to assess the visuo-spatial function since we suspected the children
      could have disturbance of this function. We did not detect this disturbance. On
      the other hand, the children had astereognosia and the right hemiparetic children
      preferred to execute signs on the right part of the computer visor. We discuss
      and propose explanations for both findings.

PMID- 8147753
TI  - [Acute bacterial meningitis: vascular complications].
AB  - The authors present the study of four children with arteritis as vascular
      complication of acute bacterial meningitis. They report pathophysiological
      mechanisms involved in vascular lesions, and progress in the understanding of
      these complications.

PMID- 8147754
TI  - [Pseudotumor cerebri without optic papilledema].
AB  - Four cases of benign intracranial hypertension in two nonobese women (23 and 35
      yr. old) and two nonobese men (both 47 yr. old) are presented. The most
      remarkable finding of the clinical investigation of these cases was the absence
      of papilledema. Our finding is consistent with other reports, and suggest that
      the presence of papilledema should not be considered critical for the diagnosis
      of benign intracranial hypertension. Additionally, the authors present a
      hypothesis for the absence of papilledema in cases otherwise typical of benign
      intracranial hypertension.

PMID- 8147755
TI  - [Carpal tunnel syndrome: retrospective study of 106 cases and complications].
AB  - The authors present a short review of anatomic and pathophysiological bases of
      the carpal tunnel syndrome, and its surgical treatment and complications. They
      report the cases of two patients who developed sympathetic alterations with hand
      edema and vascular changes (Raynaud phenomenon), and propose an explanation which
      they name "sympathetic denervation". This is the only complication of their
      series and it occurred during the immediate post-operative period, coinciding
      with removal of immobilization of the wrist on the 22nd post-operative day.

PMID- 8147756
TI  - [Cystic meningioma].
AB  - Cystic meningiomas are uncommon lesions. CT image may simulate a glial or a
      metastatic tumor with cystic or necrotic changes. The correct radiological
      evaluation and the recognition of this kind of tumor are important for surgical
      treatment since they are potentially curable neoplasms. In this paper the authors
      report their experience with the treatment of three cases of cystic meningiomas,
      and discuss some characteristics of these lesions.

PMID- 8147757
TI  - Effects of body position on sleep related disordered breathing in a patient with
      Steinert's disease.
AB  - Sudden changes in respiratory patterns observed during polysomnographic studies
      may suggest a positional form of SAHS (sleep apnea-hypopnea syndrome). We report
      the case of a 37-year-old patient with Steinert's disease with this form of SAHS.
      Breathing during sleep could be regularized by a simple positional control.

PMID- 8147758
TI  - [Segawa's disease: progressive dystonia responsive to L-dopa. A case report].
AB  - Segawa's disease (SD) is a hereditary progressive dystonia with marked diurnal
      fluctuation with onset in childhood or adolescence and a striking responsiveness
      to L-dopa. Here we describe a typical case of SD in a 28 year old woman whose
      disease begun at the age of 18 years. This patient had a second cousin with
      probable hereditary spastic paraplegia (Strumpell's familiar spastic paraplegia)
      who had no benefit on a recent L-dopa trial. Due to this family history our
      patient had been misdiagnosed as Strumpell's disease for more than 10 years.
      There was no other apparent case of SD in the family. Her father had an atypical
      gait but was otherwise normal. Her daughter had motor developmental delay due to
      hypotonia. Pes cavus was a common feature to the patient, her father and her
      cousin.

PMID- 8147759
TI  - [Chronic nervous form of Chagas disease: clinical course and anatomopathology of
      a case followed-up for 20 years].
AB  - The chronic nervous forms of Chagas' disease involve both the central and
      peripheral nervous systems although they are not detected at the frequency
      indicated by Chagas in his initial observations. The present report concerns a
      patient with chronic Chagas' disease since childhood who progressively developed
      involvement of voluntary motility, muscle tone, coordination, and cranial nerves.
      The patient also had Chagas' heart and colon disease. The patient died after
      surgery for hemicolectomy and was autopsied. Histologic study of the central
      nervous system revealed demyelination of the spinocerebellar tracts and posterior
      columns, a great reduction in the Purkinje cells number, extensive cell loss of
      the substantia nigra and locus coeruleus, lacunar state in the basal nuclei,
      tissue infiltration by aberrant Herring bodies, porencephaly, and thickening of
      the meninges.

PMID- 8147760
TI  - [Neurocysticercosis in Rio Grande do Norte before and after computed tomography:
      report of a case].
AB  - The authors emphasize the importance of computed tomography (CT) in the diagnosis
      of neurocysticercosis. Before CT, neurocysticercosis was considered rare in the
      Northeast Brazil. They reviewed fifteen cases diagnosed as neurocysticercosis by
      CT at the Institute of Radiology, in Natal. A case of neurocysticercosis
      diagnosed by CT and CSF is reported.

PMID- 8147761
TI  - [Parkinson disease induced by flunarizine: report of a case].
AB  - The authors report the case of a female patient with parkinsonism induced by
      flunarizine, and refer the tremor to be of parkinsonian and also of wilsonian
      type. Cure was observed within three months, after withdrawal of flunarizine, and
      the use of L-dopa and biperiden.

PMID- 8147762
TI  - [Scleroderma, thyroiditis, and myasthenia gravis: study of a case].
AB  - A thirty-six years old woman with myasthenia gravis developed cold intolerance
      after two years, and Hashimoto's thyroiditis diagnosis was established. Four
      years later she exhibited skin thickening (limited scleroderma). Laboratory and
      clinical findings suggested the CREST type of systemic sclerosis. Difficulty in
      scleroderma diagnosis is discussed, as overlap of syndromes. Hashimoto's
      thyroiditis and myasthenia gravis are infrequently associated. Occurrence of
      scleroderma and myasthenia gravis in the same patient is rare. The coincidence of
      these three disorders was not found in literature.

PMID- 8147763
TI  - [Traumatic diabetes insipidus: a case report].
AB  - This case report refers to a thirty-nine years old female patient with severe
      head injury and other body injuries who developed symptoms of diabetes insipidus.
      The patient died eleven days after hospital admission during which magnetic
      resonance imaging and computerized tomography were done, showing characteristic
      hypothalamic lesions. This stimulated the authors to review the literature and
      call attention to the prevention and prognosis of endocrine syndromes which may
      appear in patients secondarily and late, and whose morbidity may be decreased
      with early diagnosis and treatment.

PMID- 8147764
TI  - [Air in extradural hematoma: report of 2 cases].
AB  - The authors report two cases of the presence of free air in acute extradural
      hematomas. This is not an unusual radiological finding which has been
      infrequently reported in the literature.

PMID- 8147765
TI  - The National Confidential Enquiry into Peri-operative Deaths (NCEPOD).
AB  - The National Confidential Enquiry into Peri-operative Deaths (NCEPOD) is now
      established in the United Kingdom (excluding Scotland) as a voluntary,
      confidential system designed to review the clinical practice which precedes a
      death within 30 days of surgery. The Enquiry is comprehensive, widely
      representative and authoritative. To date, two reports have been published and
      there is an ongoing programme planned. The influence of these reports on the
      practice of anaesthesia and surgery in Britain is undeniable.

PMID- 8147766
TI  - Understanding variation: the key to cost reduction and quality improvement.
AB  - Analyses of acute hospital services in Australia reveal geographic differences in
      the rates of utilization. In order to meet the important challenge of improving
      the quality of services it is necessary to understand the nature and causes of
      the variation in these utilization measures. This paper provides examples of the
      variation in admission rates and lengths of stay for selected procedures in
      Australian States and shows that the length of stay is related to the variation
      in admission rates. It concludes that a greater understanding of both the
      admission and discharge processes is necessary to improve quality and produce
      cost savings.

PMID- 8147767
TI  - A pressure care survey in the operating theatres.
AB  - During 1988 and 1989 several patients developed severe pressure areas post
      operation. The patients all underwent major surgery lasting a few hours and
      experienced haemodynamic complications as a result of their condition in the peri
      operative period. Although these pressure areas did not develop while the
      patients were in the operating theatres it was thought that the duration of their
      surgery contributed to the problem. In order to determine the extent of pressure
      area development on patients undergoing surgery it was decided to undertake an
      extensive quality assurance audit over a 3 month period. The sample of 108
      patients included patients from cardiothoracic, orthopaedic and plastic
      microvascular, ear, nose and throat, ophthalmology, vascular, urology and general
      surgery plus a control group of patients whose surgery was less than 1 h
      duration. The patients were visited pre-operatively to assess their skin
      integrity. Intra-operative pressure care management plus other relevant
      information was documented. A second visit at 24 h post operation determined
      whether any changes in skin integrity had developed. The results of the surgery
      were not significant when the whole sample was looked at. However, they did
      become statistically significant when broken down into specialty groups. The
      recommendations of the survey included research into the improvement of operating
      table mattresses and contoured positioning devices. An education programme of
      staff was to be undertaken to develop greater awareness of the problem.

PMID- 8147768
TI  - Introduction of total quality management into a clinical chemistry laboratory.
AB  - Total quality management (TQM) was introduced into a clinical chemistry
      laboratory department. During the first 9 months, 35 quality improvement projects
      were introduced, involving 87% of the Department's staff. As a result of these
      projects and with a capped budget, a range of new clinical services was
      introduced, significant improvements in the speed of Departmental services was
      documented, productivity improvements were achieved, and a 10-fold reduction in
      staff resignations occurred. The major hindrance encountered was the lack of
      interest from other non-quality orientated departments elsewhere in the hospital.

PMID- 8147770
TI  - Neck dissection: which and when?

PMID- 8147769
TI  - A quality partnership: closing the gaps between hospital and the community.
AB  - Queensland Health is trialling an integrated package of projects aimed at
      reducing lengths of stay in public hospitals, providing continuity and quality of
      care from admission to an acute-care facility through to the completion of the
      episode in the community. Service gaps and reasons for delayed discharge are
      identified; funds are provided for the purchase of care for individual
      patients/clients; and the interface between hospital and community is co
      ordinated. Multi-disciplinary teams, including the patient's own general
      practitioner, co-operate in the referral process for the provision of care within
      the community. Clinical nurse consultants monitor quality aspects from the
      community perspective. Implementation has been approached in different ways, at
      different sites. Education of key players is an important variable in the success
      of the project.

PMID- 8147771
TI  - A code of ethics for the college.

PMID- 8147772
TI  - Quality of life as an outcome variable in oncology and surgery.
AB  - The major objective of all health interventions is to improve the quality of
      life. Assessment of the results of treatment for cancer has traditionally
      included tumour response, treatment toxicity, patient's physical performance
      status and length of survival. More recently, attempts have been made to
      incorporate quality of life assessment in oncology research and practice. The
      audit of surgical treatment includes the evaluation of process and outcome.
      Although prominence has often been given to the relatively readily identified
      negative features of operative mortality and complications, both positive and
      negative effects need to be assessed. Elective surgery may be intended to reduce
      the risk of future disease-specific mortality but it may be extremely difficult
      to establish whether this objective has been achieved. We therefore need to
      recognize that the main and legitimate aims of elective surgery are to relieve
      disability, discomfort and disfigurement. These are quality of life issues.
      Minimally invasive surgery and day surgery are examples of current practice where
      quality of life assessment is important in the thorough evaluation of their role.
      In this review the available methods of assessment of quality of life are
      examined and a case is made for their routine inclusion in the evaluation of
      treatment in oncology and surgery.

PMID- 8147773
TI  - A selective approach to neck dissection for mucosal squamous cell carcinoma.
AB  - A personal series of 189 neck dissections performed over 6 years among 154
      patients with mucosal squamous cell carcinoma is presented. The most common
      primary sites were the oral cavity (66), oropharynx (38) and hypopharynx (17).
      There were 104 therapeutic and 85 elective neck dissections. Over 40% of
      therapeutic dissections were modified or selective procedures. Radical neck
      dissection was never used electively. Seventy-eight patients (50%) had
      postoperative radiotherapy to the neck. Nodes were histologically positive in 110
      dissections overall (58%); 92% of therapeutic dissections and 17% of elective
      dissections. Extracapsular spread was present in 65% of positive dissections.
      Ipsilateral neck recurrence developed in 10 of 60 patients who had therapeutic
      radical dissections (17%) and in 2 of 44 patients who had therapeutic, modified
      or selective dissections (5%). Recurrence after elective dissection occurred in
      only one patient (1.2%). It is concluded that modified and selective neck
      dissection are safe and oncologically effective when used among selected patients
      and combined with adjuvant radiotherapy. Neck recurrence may still occur among
      patients with advanced and biologically aggressive disease despite radical
      therapy.

PMID- 8147774
TI  - Management of the malignant colorectal polyp: the importance of
      clinicopathological correlation.
AB  - The results of management of colorectal adenomas removed endoscopically and found
      to contain invasive cancer seen in a single institution over a 10 year period are
      presented. Clinical data were obtained retrospectively from patient case notes
      and all specimens were reviewed by one pathologist. Fifty-four patients with
      malignant polyps were studied after exclusion of others with polypoid carcinomas,
      epithelial misplacement and cases managed by primary segmental resection. Of the
      various considered predictors of adverse outcome, only histologically incomplete
      excision proved significant. However, when excision was considered
      macroscopically complete there was no significant association between incomplete
      histological excision and adverse outcome. Consideration should be given to
      conservative management of such cases.

PMID- 8147775
TI  - Gastric emptying in patients with gallstone disease with or without dyspepsia:
      effect of cholecystectomy.
AB  - Dyspepsia is a common complaint in patients presenting with gallstone disease.
      Since the stomach appears to be its site of origin, the present study was
      undertaken to assess gastric emptying in patients with gallstone disease and to
      find out its correlation with dyspeptic symptoms before and after
      cholecystectomy. Gastric emptying (t1/2) was prospectively assessed in 43
      patients with symptomatic gallstones (29 with and 14 without dyspepsia). These
      data were compared with that of 20 healthy volunteers (control group). Delayed
      gastric emptying (> 112 min: mean + 2 s.d. of the control group) was observed in
      18 patients (42%; P < 0.002), 10 of whom presented with dyspepsia and eight
      without (NS). Re-evaluation in 18 of the 29 patients with dyspepsia, 3 months
      after cholecystectomy, revealed complete disappearance of symptoms in three,
      improvement in 11 and no change in four patients. After 6 months, two patients
      had reverted back to their pre-operative dyspeptic status; resulting in three
      patients completely cured, nine partially cured and six without any change in
      their dyspeptic status at this time. Gastric emptying was delayed in nine of the
      18 patients before cholecystectomy. After cholecystectomy, normal emptying was
      observed in all but one patient (P < 0.005). Dyspeptic symptoms, however,
      completely disappeared in one patient, improved in five and remained unchanged in
      three. In the remaining nine patients, gastric emptying was normal both before
      and after cholecystectomy. Gallstone disease is associated with delayed gastric
      emptying but this delay was not the cause of dyspepsia in these patients.
      Cholecystectomy normalizes gastric emptying, a finding that has not been reported
      previously.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147776
TI  - Acute acalculous cholecystitis.
AB  - Ten cases of acute acalculous cholecystitis, presenting to one university
      affiliated institution, are described. These patients were predominantly older
      males with either overt vascular disease or a predisposition to vascular disease
      and were without the usual precipitating factors described for acalculous
      cholecystitis. Ultrasonography was helpful in making the diagnosis and early
      laparotomy revealed gangrenous cholecystitis in all patients, three of whom had
      perforated gall-bladders. Although there was no mortality, morbidity was high,
      and patients stayed in hospital a mean of 10.5 days. A vascular aetiology seems
      likely and early surgery is recommended to avoid the high mortality reported in
      the literature. It seems that this form of acalculous cholecystitis is different
      to that seen in other clinical settings.

PMID- 8147777
TI  - Bile leakage after laparoscopic cholecystectomy: biliary anatomy revisited.
AB  - Bile leakage from the gall-bladder bed following laparoscopic cholecystectomy is
      recognized as a potential cause of major morbidity. This problem is usually
      attributed to division of ducts draining a portion of liver directly into the
      gall-bladder. The authors' experience, however, and a review of the literature
      suggests that injury to a superficial duct draining into the major hepatic ducts
      rather than the gall-bladder is the principal cause of this problem. Three
      patients with bile leakage demonstrated on postoperative biliary tract imaging
      are presented with a discussion of the literature.

PMID- 8147778
TI  - Epidemiology of chronic leg ulcers in Australia.
AB  - The aim of this study was to determine the point prevalence of ulceration of the
      leg in an Australian community. This was a population-based epidemiological
      study. Two hundred and fifty-nine patients with leg ulceration were identified by
      health care professionals of all types working in hospitals and private
      practices, as well as by self referral from patients. The base population in the
      study area was 238,000. The following data were recorded: age, sex, site of
      ulceration, duration of ulceration, history of previous ulceration and patient
      mobility. The point prevalence was 0.11%. The male:female ratio was 1:1.9;
      however the age related prevalence was similar for both sexes. The age related
      prevalence of ulceration was similar to that found in two similarly conducted
      studies in the United Kingdom. The ulcers were a chronic problem with 24% having
      been present for more than 1 year. Thirty-five per cent of patients had had a
      problem of ulceration for more than 5 years and 20% had suffered 10 or more
      episodes of ulceration. Related immobility was a prominent factor with 45% of
      patients being housebound. Chronic ulceration of the leg is a common recurrent
      problem in the elderly population and is likely to increase as the population
      grows. There is a definite need to improve the method of treating this problem.

PMID- 8147779
TI  - Laparoscopic marsupialization of liver cysts.
AB  - The majority of benign, non-parasitic liver cysts are asymptomatic. Surgical
      treatment is reserved for symptomatic patients and frequently involves partial
      excision or marsupialization via a laparotomy. Surgery is occasionally offered
      for asymptomatic large cysts, where complications of cyst rupture, intra-cystic
      bleeding and infection are more common. The authors describe three cases of
      symptomatic liver cysts that were effectively marsupialized laparoscopically with
      good results.

PMID- 8147780
TI  - Transhepatic fenestration of liver cyst: a further application of laparoscopic
      surgery.
AB  - Surgery is indicated for the treatment of highly symptomatic liver cysts in adult
      polycystic liver disease. Several options are available, including liver
      resection, but surgical morbidity in a benign condition may be unacceptable. The
      authors report the transhepatic fenestration of a liver cyst under laparoscopic
      guidance in a 47 year old Chinese male. There was an excellent clinical outcome
      and minimal morbidity. Laparoscopic treatment is both effective and minimally
      traumatic, which is appropriate for a condition that will inevitably progress.

PMID- 8147781
TI  - The role of the kidney in the clearance of calcitonin gene related peptide
      (CGRP).
AB  - Calcitonin gene-related peptide (CGRP) is a 37 amino-acid peptide, undetectable
      in the plasma in health but elevated in certain disease states such as medullary
      thyroid cancer, and potentially causes symptoms. The kidney is a major site of
      and influence on the clearance of exogenously infused CGRP. As CGRP might cause
      symptoms in renal dysfunction, this study was performed to determine the
      clearance of CGRP in humans and animals with altered renal function. In chronic
      renal failure patients, CGRP was not detected in plasma either before or after
      haemodialysis. In sheep, before and after bilateral nephrectomy, there was an
      approximate halving of plasma clearance and doubling of the circulating half-life
      of infused CGRP. This reduction in clearance was greater than that which could be
      accounted for by the reduction in degradation by renal substance alone. This
      renal influence on extra-renal CGRP metabolism was not due to the renal
      production of a circulating peptidase as evidenced by the absence of such
      peptidase in the plasma of normal and anephric sheep. Further, severity of
      uraemia had no influence on the extra-renal metabolism. The mechanism by which
      the kidney influences the extra-renal metabolism of CGRP remains obscure.

PMID- 8147782
TI  - Selection of medical students: time to change.

PMID- 8147783
TI  - Perce the permissive pathologist: a cautionary tale of one who misdiagnosed a
      pseudosarcoma, killed the patient and was found out.
AB  - Perce, a promising young trainee pathologist, correctly recognizes a biopsy of a
      benign pseudosarcoma but his diagnosis is overruled by the less well read Head of
      Pathology. Acting under instructions from his Chief, Perce knowingly and without
      protest 'signs out' this benign condition as a sarcoma. The surgeon accepts the
      diagnosis without question and performs radical surgery, which is complicated by
      postoperative haemorrhage from which the patient dies. The Coroner orders a
      review of the slides and the misdiagnosis is discovered. Perce's defense that he
      did as he was told is rejected; he is forced to quit pathology and becomes an
      administrator. This unfortunate tale, which is related in verse, is intended to
      stress the importance of such benign but uncommon pseudosarcomas as nodular
      fasciitis, proliferative myositis, myositis ossificans, postoperative spindle
      cell nodule, pseudosarcoma of the bladder and juxta-articular myxoma. The poem
      also implies that surgeons should not carry out radical surgery based on an
      uncommon pathological diagnosis without checking on the adequacy of consultation
      and informed review of the sections.

PMID- 8147784
TI  - Synchronous carcinoma of the gall-bladder in patients with bile duct carcinoma.

PMID- 8147785
TI  - Resuscitation following injury: an end or a means?

PMID- 8147786
TI  - Anal lymphoma presenting as a perianal abscess.
AB  - A case of perianal abscess secondary to anal lymphoma affecting a human
      immunodeficiency virus negative patient is presented. Causes of perianal abscess
      other than anal glandular infection are important, although the proportion of
      abscesses reported to be secondary to these other causes is found to vary widely
      in the literature. A biopsy of the wall of an anorectal abscess should be taken
      when suspicion of an unusual cause arises.

PMID- 8147787
TI  - Trichobezoars.
AB  - Trichobezoars are a rare cause of upper gastrointestinal symptoms and most
      commonly occur in young females with trichophagia. A case, occurring in a 19 year
      old woman, complicated by transient pancreatitis and jejunal perforation, is
      presented.

PMID- 8147788
TI  - Post-traumatic chronic false aneurysm of the ascending aorta with long-term
      survival.
AB  - The case of a patient with impending rupture of a post-traumatic chronic false
      aneurysm of the ascending aorta is presented. It is stressed that chronic false
      aneurysms of the ascending aorta are rare and that a chronic false aneurysm of
      any part of the aorta carries a high risk of delayed rupture at any time.

PMID- 8147789
TI  - Thyroid gland metastasis from renal cell carcinoma masquerading as nodular
      goitre.
AB  - Renal cell carcinoma metastasizing to the thyroid gland, in a 72 year old
      Japanese woman, is reported. The patient had undergone a left radical nephrectomy
      for renal cell carcinoma 3 months prior to the present operation. The patient
      noticed a nodular goitre but there was no evidence of any systemic spread of
      renal cell carcinoma. The histopathologic diagnosis, from a left lobectomy of the
      thyroid gland, was thyroid gland metastasis from renal cell carcinoma in
      adenomatous goitre. Clinical manifestation of thyroid gland metastasis from renal
      cell carcinoma, with no evidence of systemic involvement, is seen rarely. A case
      is reported and the condition discussed briefly.

PMID- 8147790
TI  - How then shall we teach...?

PMID- 8147791
TI  - Tuberculous radiculomyelitis (arachnoiditis): myelographic (and CT myelographic)
      appearances.
AB  - Tuberculous radiculomyelitis (arachnoiditis) remains one of the important causes
      of paraplegia in India. The diagnosis usually rests on clinical history and
      examination, and on laboratory findings in the cerebro-spinal fluid (CSF). Few
      descriptive reports are available of the myelographic appearance, with water
      soluble contrast media, in tuberculous radioculomyelitis (arachnoiditis). A
      retrospective review of 21 myelograms and 10 computed tomographic (CT)
      myelograms, in 14 patients with tuberculous radiculomyelitis, was carried out,
      with a view to describing, in detail, the radiographic features. An attempt was
      made to assess the use of the radiologic procedures in diagnosis and follow up in
      these patients. Conventional myelographic findings included block (8/14),
      irregular subarachnoid space (9/14), filling defects (8/14), sluggish contrast
      flow (2/14), root thickening (3/14) and atrophic cord (2/14). Computed
      tomographic myelography showed reduced contrast density in portions of the
      opacified CSF ring around the cord in affected region (6/7) and, in addition,
      demonstrated septa and adhesions. Intravenous contrast CT was not found to be
      useful (2/2). Follow-up studies showed partial resolution (3/6), deterioration
      (1/6) and status quo of radiological findings (2/6). Although these changes can
      be seen in chronic radiculomyelitis (arachnoiditis) from other causes, such as
      leukaemic infiltration/lymphoma, other chronic central nervous system infections
      and iatrogenic causes, including repeated intrathecal injections, conventional
      myelography appeared to be useful for diagnosis and follow up in tuberculous
      radiculomyelitis (arachnoiditis).

PMID- 8147792
TI  - Incidence of the empty delta sign in computed tomography in the paediatric age
      group.
AB  - The computed tomographic (CT) appearances of dural sinus thrombosis are variable,
      but include visualization of thrombus within the sinus on post-contrast images
      (the 'empty triangle' or 'empty delta' sign). This review of 104 consecutive
      examinations was undertaken to assess the incidence of the empty delta sign in a
      paediatric group undergoing CT examinations. The number of examinations in which
      a sagittal sinus filling defect was seen in three or more images, was
      unexpectedly high. An overall incidence of 18% was noted. Defects due to bone
      artifact and defects seen on only one or two slices were excluded. The age
      distribution of abnormal scans was markedly skewed towards young infants. Nine of
      27 examinations (33%) in infants less than 1 month of age, were positive for
      filling defects, compared with six of 21 (29%) aged between 1 and 12 months, and
      four of 56 (7%) aged over 1 year. This review suggests that the finding of a
      filling defect or empty delta sign in the sagittal sinus is not pathognomonic for
      sinus thrombosis that results in clinically apparent manifestations. Second, a
      filling defect apparent on CT may resolve spontaneously. The incidence of non
      occlusive sinus thrombosis may be significantly higher than previously
      recognized, particularly in young infants where predisposing conditions including
      dehydration, infection or prematurity coexist. Previous studies have indicated
      that the sensitivity of the empty delta sign is approximately 30%. This study
      implies that either the empty sign has limited specificity in the paediatric
      population, or that unrecognized non-occlusive sinus thrombosis is much more
      frequent than previously described.

PMID- 8147793
TI  - Authorship ethics in the radiological sciences.
AB  - The written communication of new ideas and current developments is a crucial part
      of the progress of radiological sciences. Research results cannot be incorporated
      into the body of scientific knowledge, unless they are published. In radiology,
      questions on authorship ethics have received limited attention. Among the topics
      discussed in this article are the incentives that stimulate radiologists to write
      and the obstacles to successful authorship. Practices causing concern to editors,
      authors and readers are examined, such as the excessive growth through recent
      years in the numbers of authors per paper, unjustified co-authorships, wasteful
      publication practices and fraudulent research. The relationship between the
      abuses of authorship and the pressure exerted on researchers to publish is
      exemplified. Further issues addressed include the responsibilities of authors,
      the proposed principles for authorship, the determination of the sequence of
      authors in multi-authored papers and the concept of publication credit. The
      editor's role in preventing unethical authorship is examined and emphasis is
      placed on the proposals that have been made to achieve the required reforms by
      eradicating the publish or perish mentality.

PMID- 8147794
TI  - Doses in mammography: from the phantom to the patient.
AB  - While the use of a reference phantom is essential for dosimetry in acceptance
      testing and in regular quality control checks of a mammographic X-ray unit, it is
      also of importance to be able to estimate the patient dose in each individual
      investigation. Radiographic and physical data were analysed for a total of 212
      women who between them were screened at three locations participating in a breast
      screening programme. The radiologists made estimates of the individual breast
      composition (% glandular/adipose ratio) at the film reporting sessions, and then
      the glandular doses were calculated by the auditor according to the NCRP 85
      methodology. Arising from the data analysis of this dosimetry survey, a method is
      proposed to determine objectively patient breast composition from the photo-timed
      mAs for a given film optical density setting. This permits the NCRP calculations
      to be extended from breasts of 'average' (50/50) composition to breasts of
      individually determined composition. The diversity of the results between the
      three locations emphasises the need for regular audits of a mammographic X-ray
      unit's performance by an experienced radiological physicist, at least annually or
      after any major interventional service on the unit.

PMID- 8147795
TI  - Technetium-99m DTPA renography and angiography in renal artery stenosis of
      varying severity.
AB  - Thirty-five hypertensive patients, consecutively studied between 1986 and 1991,
      were retrospectively reviewed, to compare Technetium-99m (99mTc) DTPA renal
      scanning for renal artery stenosis with angiography. Ten patients were on chronic
      angiotensin converting enzyme (ACE) inhibitor medication and 20 underwent
      angioplasty of their stenoses. In patients not on ACE inhibitors the renal scan
      specificity was 83%, sensitivity 82%, negative predictive value 89% and positive
      predictive value 74%. In the 10 patients on ACE inhibitors the specificity was
      67% (relatively more stenoses of < 50% were reported in this group), sensitivity
      100%, negative predictive value 100% and positive predictive value 60%. Low
      levels of function (< 10 mL/min/1.73m2) in 9 kidneys did not militate against
      diagnoses that correlated well with angiography. Hence, renal scanning,
      particularly with ACE inhibition, is efficacious in the evaluation of possible
      renal artery stenosis. With a mean follow-up period of 29 months after
      percutaneous transluminal angioplasty (PTA), four patients had clinical
      improvement of hypertension control. Each had pre-PTA total glomerular filtration
      rates (GFR) of approximately 75 mL/min/1.73m2. No improvement was detected in
      cases with pre-PTA total GFR of < 50 mL/min/1.73m2. This may be the level of
      renal function below which PTA therapy or surgery will not provide benefit.

PMID- 8147796
TI  - Cholecystokinin (CCK)-HIDA scintigraphy in patients with suspected gall-bladder
      dysfunction.
AB  - Cholecystokinin hepatobiliary (CCK-HIDA) scintigraphy is used to triage patients
      with chronic abdominal pain and suspected gall-bladder dysfunction. This study
      evaluates the predictive value of CCK-HIDA for clinical outcome after surgical
      and medical therapy. Fifty-six patients (45 females), mean age 43 +/- 9 years,
      with otherwise normal investigations, including normal ultrasound, fasted for
      more than 8h and then had 70MBq technetium-99m-EHIDA injected. One and a half
      hours later 15 ng/kg CCK was infused over 45 min. Seventy minutes dynamic imaging
      commenced 5 min prior to infusion. An abnormal gall-bladder ejection fraction
      (GBEF) was defined as < 50%. Patients were treated medically, or by
      cholecystectomy, depending on the surgeon's overall assessment, including results
      of the CCK-HIDA study. Patient status was then obtained in 51/56 patients at
      least 3 months after the scan or at least 1 month after surgery. All surgical
      specimens were reviewed independently for pathological changes of chronic
      acalculous cholecystitis. Of the 11 patients with an abnormal gall-bladder
      ejection fraction, nine (82%) underwent cholecystectomy, all of whom achieved
      total symptomatic cure, while two patients underwent other therapy, both of whom
      remained symptomatically unchanged. Of the 40 patients whose gall-bladder
      ejection fraction was normal, only five (12.5%) underwent cholecystectomy, of
      whom four were cured and one partially improved at follow up. Of the 35 patients
      with a normal gall-bladder ejection fraction and who underwent forms of therapy
      other than cholecystectomy, nine were cured symptomatically, 13 improved, 10
      remained unchanged and three were symptomatically worse at follow up.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8147797
TI  - Exploring the role of educational videos in radiation oncology practice.

PMID- 8147798
TI  - Fellowship training in radiation oncology: an Australasian survey of current
      teaching and perceived needs.
AB  - Thirty Australian and New Zealand Radiation Oncology registrars, who were
      preparing for their final qualifying examinations, were surveyed about their
      attitudes to their training programmes. While two (7%) indicated that they had no
      structured tuition whatsoever, the majority 19 (63%) received on average 1-2h per
      week, which was much less than their perceived need. Other areas of training
      considered deficient included exposure to curriculum requirements, peer support
      and access to other hospital specialty meetings. When asked about the concept of
      job rotation between training centres, 23 (77%) considered it to be potentially
      advantageous, with a majority preferring one such rotation of 6-12 months
      duration occurring in their third year, with a return to their base unit prior to
      final qualifying examinations. Limitations and potential benefits of the job
      rotation concept are discussed.

PMID- 8147799
TI  - Cryptogenic organizing pneumonia with atypical histopathological features.
AB  - A case report of cryptogenic organizing pneumonia (COP); also known as
      bronchiolitis obliterans organizing pneumonia (BOOP) is presented. The
      histopathologic findings of COP are well documented in the literature and
      typically consist of organizing pneumonia of uniform appearance. This case report
      describes, in addition to the classic findings, more acute exudative inflammation
      not usually associated with this condition. Variation in the evolution of the
      pneumonic process is one of the reasons for reporting this case. The promotion of
      awareness of this treatable condition is the other reason for reporting this
      case. When multifocal areas of consolidation are demonstrated radiologically,
      particularly when peripheral and basal, and in the correct clinical setting, the
      possibility of COP should be entertained. This condition responds dramatically to
      steroid therapy, and has a good prognosis.

PMID- 8147800
TI  - The hypo-echoic cortical rim in lupus nephritis.
AB  - Hypo-echoic cortical rims are an unusual ultrasound finding in patients with
      renal disease. A case report is presented of a patient with lupus nephritis who
      demonstrated hypo-echoic cortical rims. A brief review of the pathological causes
      of hypo-echoic cortical rims is given.

PMID- 8147801
TI  - Sonographic findings in bladder haematoma.
AB  - The medical imaging and clinical histories of three cases of haematoma of the
      urinary bladder in paediatrics were reviewed retrospectively. The sonographic
      findings are unique and diagnostic. Three distinctive sonographic features were
      observed. The haematomas were large, occupying most of the bladder lumen. They
      showed an echogenic thick, smooth rim and, in two cases, a laminated appearance
      with concentric layers of alternating hyperechogenicity and hypo-echogenicity.

PMID- 8147802
TI  - Self-contained, inflatable penile prosthesis: magnetic resonance appearance.
AB  - The appearance of an inflatable penile prosthesis, visualized on a short tau
      inversion recovery sequence, is reported, in a patient who had magnetic resonance
      imaging for pelvic pain subsequent to radical cystoprostatectomy for bladder
      carcinoma. With suppression of adjacent fat signal, the prosthesis is well
      delineated from adjacent structures. The fluid-containing cylinders of the
      prosthesis are of very bright signal intensity, with the relief valve assembly of
      low signal intensity.

PMID- 8147803
TI  - Osteomesopycnosis.
AB  - The radiographic findings in two children with osteomesopycnosis are described.
      This is the first report in the Australian literature of this uncommon, recently
      described entity.

PMID- 8147804
TI  - Mesomelic dysplasia: Langer type.
AB  - Two patients with Langer type mesomelic dysplasia are reported. This is one of
      the rare but well differentiated and easily recognizable mesomelic dysplasias.

PMID- 8147805
TI  - Comparison of magnetic resonance imaging and computed tomographic discography in
      the assessment of lumbar disc degeneration.
AB  - Eighteen patients with chronic low back pain were studied with magnetic resonance
      imaging (MRI) and computed tomographic (CT) discography. Each study was
      classified as being normal, showing early disc degenerative changes including
      annular tear, showing established disc degeneration or disc herniation. There was
      comparable information in over 90% of the MRI studies when compared to CT
      discography, without reliance on pain provocation or carrying out an invasive
      procedure. The axial and sagittal T1 weighted images were used to exclude other
      causes of pain, such as foraminal stenosis and disc herniation. The mid-sagittal
      T2 weighted image used in this study was considered to be, in part, responsible
      for the underestimation of disc degeneration because it did not allow
      visualization of the lateral aspects of the discs.

PMID- 8147806
TI  - Hepatic uptake of a bone scan agent (99mTc-MDP) in a patient with amyloidosis
      associated with plasma cell dyscrasia.
AB  - This case report describes diffuse hepatic uptake of a diphosphonate bone scan
      agent (Technetium-99m-MDP) in a patient with amyloidosis associated with a plasma
      cell dyscrasia. Amyloid infiltration is one of the more rare, but well
      recognized, causes of hepatic uptake of bone scan tracer. Other causes are also
      discussed in this case report.

PMID- 8147807
TI  - The falling anterior labrum.
AB  - Two cases of a falling anterior glenoid labrum are presented. The anterior labrum
      appears normal on supine double contrast computed tomographic arthrography
      (DCCTA). However, on prone DCCTA the anterior labrum falls away from the glenoid.
      The addition of prone DCCTA in these two cases reveals a labral tear, occult on
      routine supine DCCTA.

PMID- 8147808
TI  - Richter's hernia of the splenic flexure: computed tomography appearances.
AB  - A case of a clinically occult Richter's hernia of the splenic flexure, through an
      anterior abdominal wall defect, is described. In view of the initial absence of
      bowel obstruction with a partial or Richter's hernia, and in the absence of
      physical findings, the importance of computed tomography (CT) in demonstrating
      abdominal wall lesions is highlighted.

PMID- 8147809
TI  - Appendicitis: an unusual cause of infected abdominal aortic aneurysm.
AB  - An unusual case of appendicitis, which presented as an infected aortic aneurysm
      is described. Gas was noted in the wall of the aneurysm on abdominal radiographs
      and computed tomography, due to the formation of an appendico-aortic fistula.
      Computed tomography also demonstrated a contained rupture of the aneurysm.

PMID- 8147810
TI  - Interventional radiology in the management of superior thyroid artery injury
      which presents as a diagnostic dilemma.
AB  - Following a forgotten iron splinter injury, a 19 year old male developed a slowly
      increasing extrathyroidal haematoma, which presented as a diagnostic dilemma.
      Surgical exploration failed to establish a diagnosis and was complicated by
      severe haemorrhage. Emergency angiography demonstrated injury to the superior
      thyroid artery. Therapeutic embolization and surgical exploration resulted in
      functional and anatomical recovery of the thyroid lobe.

PMID- 8147811
TI  - Intracranial aspergillosis producing cavernous sinus syndrome and rupture of
      internal carotid artery.
AB  - A case of invasive, intracranial aspergillosis in a non-immunocompromised
      patient, complicated by rupture of the internal carotid artery due to fungal
      arteritis, is presented. The computed tomography and magnetic resonance imaging
      findings are discussed. This is a rare condition with a poor prognosis and
      requires a high level of suspicion when paranasal sinus disease is detected.

PMID- 8147812
TI  - Atypical fat necrosis of the breast: the 'mycetoma' appearance.
AB  - A very unusual appearance of fat necrosis in the breast is described. The low
      density/hypo-echoic rim and high density/hyperechoic central part are shown on
      mammography and ultrasound, respectively. The mass had the appearance of a
      'mycetoma' in a cavity in the lung. The radiological diagnosis of fat necrosis
      was confirmed by histopathology.

PMID- 8147813
TI  - Self-expandable stents for tracheal stenosis: experience in two patients.
AB  - Two patients with cervical tracheal stenosis, following prolonged ventilatory
      support, underwent balloon dilatation and expandable stainless steel stent
      placement across the stenoses. Following the successful release of the stent,
      there was gradual widening of the stenosed trachea in one patient, while in the
      other re-stenosis occurred due to columns of tracheal tissue projecting between
      the limbs of the stent. In the chronically ill and debilitated, use of expandable
      stents provides a good alternative to complex reconstructive surgery.

PMID- 8147814
TI  - Low dose rate teletherapy and tumour response.

PMID- 8147815
TI  - Radiology of starch granulomatous peritonitis.

PMID- 8147816
TI  - Alcohol for simple parenchymal cysts.

PMID- 8147817
TI  - Irradiation of the prostate: another holocaust?

PMID- 8147818
TI  - The ERabp gene family: structural and physiological analyses.

PMID- 8147820
TI  - Field stimulation-induced noradrenaline release from guinea-pig atria is
      modulated by prejunctional alpha 2-adrenoceptors and protein kinase C.
AB  - Guinea-pig left atria were loaded with 10 microCi 7-[3H]noradrenaline, and
      noradrenaline release from sympathetic nerve endings was then elicited by
      refractory period field stimulation. When one pulse of 0.2 ms duration was
      applied during each refractory period, the resulting transmitter release was
      halved by 3 x 10(-7) mol/l of the alpha 2-adrenoceptor agonist clonidine and
      increased about 2.5-fold by either 3 x 10(-7) mol/l of the alpha 2-adrenoceptor
      antagonist idazoxan, 5 x 10(-3) mol/l of the potassium channel blocker
      tetraethylammonium chloride (TEA) or 3 x 10(-7) mol/l phorbol-12-myristate-13
      acetate (PMA), an activator of protein kinase C (PKC). Phorbol-12-myristate-13
      acetate-4-O-methylether, a compound which does not stimulate PKC, was
      ineffective. The stimulatory effect of PMA was antagonized by 7 x 10(-5) mol/l of
      the PKC inhibitor polymyxin B. No significant transmitter release was observed
      when either PMA or TEA was applied together with 10(-7) mol/l of the sodium
      channel blocker tetrodotoxin. Combinations of either idazoxan and TEA or PMA and
      TEA caused greater increases of the noradrenaline release than any individual
      drug given alone. Thus, different mechanisms of action seem to mediate the
      increase of noradrenaline release by action potential prolongation on the hand
      and activation of PKC or inhibition of alpha 2-adrenoceptors on the other hand.
      In contrast, the effects of idazoxan and PMA were not additive, which suggests a
      common mechanism of action. In atria pretreated for 10 min with 10(-4) mol/l N
      ethylmaleimide, an alkylating agent which inactivates Gi-proteins neither
      idazoxan nor PMA caused a significant increase of the stimulation-induced
      transmitter release, while TEA was still effective. When a train of four pulses,
      lasting 0.05 ms each, was applied during each refractory period, the resulting
      transmitter release was not modified by idazoxan or PMA, but was significantly
      increased by TEA. From these results, a scheme is proposed which links the
      regulation of noradrenaline release by prejunctional alpha 2-adrenoceptors and
      protein kinase C via an influence on a common inhibitory Gi-protein.

PMID- 8147819
TI  - Oxidative substrate metabolism during postischemic reperfusion.
AB  - Myocardial reperfusion occurs in a number of clinical conditions which include
      unstable angina, thrombolytic therapy or percutaneous transluminal angioplasty
      during evolving myocardial infarction and cardioplegic arrest during cardiac
      surgery. The transition from the ischemic to the postischemic state of the
      myocyte is associated with a number of functional, morphological, ionic and
      metabolic alterations. This article reviews available information on metabolism
      of glucose and palmitate in postischemic myocardium. Overall oxidative metabolic
      rate recovers rapidly after the onset of reperfusion. In some studies myocardial
      oxygen consumption during early reperfusion has been disproportionately high
      compared to contractile function. Oxygen consumption may recover transiently even
      in myocardium that undergoes irreversible injury. There exists some evidence
      indicating that cytoplasmic calcium overload may lead to increased energy
      expenditure during reperfusion. The relative contribution of fatty acids and
      glucose to oxidative metabolism during the first hour of reperfusion has been
      found either to be unchanged or to exhibit a shift toward increased glucose
      oxidation. Several observations suggest that glucose utilization may be essential
      during reperfusion for the survival of the myocardium.

PMID- 8147821
TI  - Effect of stimulation and veratrine on total cellular calcium in rat and guinea
      pig ventricular myocytes.
AB  - In rat cardiac myocytes, calcium efflux by Na+/Ca(2+)-exchange is expected only
      during ventricular systole following initial action potential repolarization. In
      contrast, in guinea-pigs, calcium influx via Na+/Ca(2+)-exchange is expected only
      during the initial portion of the action potential. Thus electrical stimulation
      is expected to result in reduced intracellular calcium ([Ca2+]i) in rat and an
      increase in guinea pig. We tested this hypothesis by measuring total cellular
      calcium ([Ca]tot) using 45Ca following stimulation of isolated rat and guinea-pig
      ventricular myocytes. Many studies have also emphasized that the rate and the
      direction of Na+/Ca(2+)-exchange across the sarcolemma are in part dependent on
      the magnitude of the transsarcolemmal sodium gradient. Thus, increasing
      intracellular sodium ([Na+]i) is expected to result in an increased [Ca2+]i. This
      hypothesis was also tested by measuring [Ca]tot following veratrine
      administration. Enzymatically isolated rat and guinea-pig ventricular myocytes
      were divided into two groups; non-stimulated and stimulated (1 Hz). The
      concentration-dependent effects of veratrine (1,10,100 micrograms/ml) on [Ca]tot
      were determined in both these groups. In the absence of veratrine, non-stimulated
      rat myocytes had a significantly higher [Ca]tot than did stimulated ones. Non
      stimulated guinea-pig myocytes had a significantly lower [Ca]tot when compared
      with stimulated ones. Veratrine increased [Ca]tot in both species in a
      concentration-dependent fashion. In addition, following veratrine the difference
      between [Ca]tot in non-stimulated and stimulated rat myocytes was no longer
      significant. These results support those of others who have demonstrated that
      stimulation is associated with a gain of cellular calcium in both rabbit and
      guinea-pig ventricle and a calcium loss in rat ventricle.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8147822
TI  - Influence of 2,3-butanedione monoxime on heart energy metabolism.
AB  - The influence of 2,3-butanedione monoxime (BDM) on function and subcellular
      energy status in isolated perfused guinea pig hearts was examined during ischemia
      and reperfusion. For this purpose the mitochondrial and extramitochondrial
      contents of ATP, ADP, creatine phosphate (CrP) and creatine (Cr) were determined
      after fractionation of freeze-clamped heart tissue in non-aqueous solvents.
      Furthermore, the inhibitory action of this compound on isolated cardiac
      mitochondria and the actomyosin-ATPase was studied. BDM in the millimolar range
      inhibited both the actomyosin-ATPase in skinned-fibers (IC50 22 mM) and the
      electron transport chain in isolated mitochondria (IC50 28 mM). In normoxia at 35
      degrees C the contractile function of isolated guinea pig hearts was completely
      inhibited and oxygen consumption was markedly reduced (-60%) by 30 mM BDM. The
      mitochondrial and extramitochondrial contents of adenine nucleotides (sum of ATP
      + ADP) and total creatine (sum of CrP + Cr) as well as the extramitochondrial
      ATP/ADP- and CrP/Cr-ratios were decreased. Similar changes, significantly more
      pronounced, however, were found after 30 min of warm (35 degrees C) ischemia.
      However, if hearts were exposed to BDM during cold ischemia, extramitochondrial
      ATP/ADP- and CrP/Cr-ratios were increased compared to BDM-free controls. If
      hearts were exposed to BDM during ischemia (at 35 degrees C) and were then
      reperfused BDM-free, ATP/ADP- and CrP/Cr-ratios were decreased. However, if
      hearts were exposed to BDM during cold ischemia and were then reperfused BDM
      free, extramitochondrial ATP/ADP- and CrP/Cr-ratios were unchanged. These results
      confirm earlier studies on the tissue protective action of BDM but point to the
      importance of low temperature exposure to BDM for its beneficial effect.

PMID- 8147823
TI  - Improved functional recovery after ischemic preconditioning in the globally
      ischemic rabbit heart is not mediated by adenosine A1 receptor activation.
AB  - Experiments were carried out to test the hypothesis that preconditioning reduces
      the impairment of recovery of cardiac mechanical function and that this effect is
      mediated by activation of adenosine A1 receptors. Isolated hearts were
      Langendorff-perfused at 37 degrees C with oxygenated blood and paced at 3 Hz.
      They were divided into 5 groups, all subjected to 45 min global ischemia followed
      by one hour of reperfusion: 1) Control hearts (n = 7) which received no treatment
      or short ischemia before the long ischemia, 2) preconditioned hearts (n = 7),
      submitted to 5-min zero-flow global ischemia, followed by 5 min reperfusion
      before the long ischemia, 3) hearts pretreated with sulfophenyltheophylline (SPT
      100 microM) before preconditioning and long ischemia (n = 6), 4) hearts in which
      preconditioning was substituted by administration of 10 microM phenyl-isopropyl
      adenosine (PIA) over 5 min, and 5) hearts in which preconditioning was
      substituted by the administration of 1.5 mg adenosine over 5 min. Hemodynamic
      results show significant improvement of the postischemic recovery of left
      ventricular developed pressure (DP) by preconditioning. SPT pretreatment did not
      reverse the improvement of recovery, obtained by preconditioning, whereas PIA
      treatment could not mimic preconditioning. Adenosine treatment caused some
      improvement of recovery of DP, but which remained lower compared to that caused
      by preconditioning. The contracture developed during ischemia persisted in
      control hearts, whereas contracture disappeared in non-treated preconditioned
      hearts. SPT did not prevent the decrease in contracture by preconditioning
      although values remained slightly higher than in the non-treated preconditioned
      hearts. PIA did not substitute for preconditioning in preventing contracture. In
      the adenosine treated group, some decrease of contracture occurred during
      reperfusion, but values remained significantly higher than in preconditioning. We
      conclude that receptor A1 activation is not the main mechanism underlying
      improved functional recovery conferred by preconditioning since an A1 receptor
      blocker (SPT) cannot reverse the effect of preconditioning and an A1 receptor
      agonist (PIA) cannot mimic it. Administration of exogenous adenosine reduces
      functional impairment to a certain extent, but less than preconditioning.

PMID- 8147824
TI  - Reduction of regional contractile function by preconditioning ischemia does not
      play a permissive role in the infarct size-limitation by the preconditioning.
AB  - Although previous studies have shown that preconditioning cannot be explained by
      concurrent myocardial stunning alone, it remains unclear whether reduction of
      contractile function by preconditioning ischemia is required for its
      cardioprotective effect. The present study examined whether preconditioning
      occurs in the absence of regional contractile dysfunction. In the first series of
      experiments, rabbits received two cycles of 2-min coronary occlusion separated by
      5-min reperfusion, with or without dobutamine infusion (10 micrograms/kg/min,
      i.v.) commencing before the onset of ischemia. Regional thickening fraction
      measured by epicardial Doppler sensor was 72.8 +/- 4.7% of baseline (mean +/-
      SEM) in the untreated group and 102.9 +/- 3.1% in the dobutamine group at the end
      of the second cycle of ischemia/reperfusion. In the second series of the study,
      four groups of rabbits underwent 30-min coronary occlusion and reperfusion. The
      control group was untreated, and the PC group was preconditioned with two cycles
      of 2-min ischemia/5-min reperfusion before the 30-min ischemia. The PC-DOB group
      received both preconditioning and dobutamine infusion (10 micrograms/kg/min,
      i.v.), which was started 5 min before the preconditioning and continued for 19
      min. The DOB group was given dobutamine infusion like the PC-DOB group, but was
      not preconditioned. After 72-h reperfusion, infarct size and area at risk were
      determined by histology and fluorescent particles, respectively. Infarct sizes in
      the PC and PC-DOB groups (25.0 +/- 3.4% and 22.7 +/- 3.3% of area at risk,
      respectively) were significantly smaller than that in the control group (48.2 +/-
      2.6%). In the DOB groups, infarct size (43.5 +/- 4.0%) was similar to the control
      value. Infusion of dobutamine at a dose sufficient to abolish the contractile
      dysfunction which would have been induced by ischemic preconditioning did not
      attenuate the infarct size-limiting effect of preconditioning. Thus, it is
      unlikely that reduction of contractile function plays a permissive role in the
      appearance of the cardioprotective effect of preconditioning.

PMID- 8147827
TI  - Regional blood flow and contractile function: are they matched in normal,
      ischemic and reperfused myocardium?
AB  - One central hypothesis of cardiovascular physiology has been a balance between
      myocardial blood flow and contractile function during natural conditions, i.e.
      supply and demand are matched. This hypothesis was derived from studies relating
      total coronary blood flow to global ventricular function. The present article
      examines the relationship between myocardial blood flow and function on a
      regional level. In normal myocardium, considerable heterogeneity of blood flow
      exists, indicating similar heterogeneity of metabolic demand and potentially also
      function. However, when the degree of metabolic coupling between flow and
      function is questioned, there is no evidence whether or not flow and function are
      matched on a regional level. One closely related hypothesis of cardiovascular
      pathology has been an imbalance or mismatch between supply and demand during
      ischemia. Because myocardial function rapidly declines during early ischemia,
      residual, regional myocardial blood flow and function may be once again matched
      on a lower level. Such low-level supply-demand balance may persist over prolonged
      periods of ischemia and permit the myocardium to remain viable, i.e. the
      myocardium can "hibernate." Analyzing myocardial blood flow and function on a
      regional level has generated new insight into strategies of adaptation to the
      adverse situation of reduced blood flow. Whereas in hibernating (ischemic)
      myocardium, regional myocardial blood flow and function are matched, flow and
      function appear to be unmatched in reperfused, dysfunctional, i.e. 'stunned'
      myocardium. "Stunned myocardium" appears once more as a result of a strategy of
      adaptation, as the preceding ischemia did not induce irreversible myocardial
      damage but preserved the ischemic myocardium viable, although functionally
      impaired.

PMID- 8147825
TI  - Reduced 3H-ouabain binding site (Na,K-ATPase) concentration in ventricular
      myocardium of dogs with tachycardia induced heart failure.
AB  - The present study evaluates 3H-ouabain binding site (Na,K-ATPase) concentration
      in left ventricular myocardium of dogs with heart failure induced by tachycardia
      as a result of ventricular pacing. Samples of left ventricle were obtained from
      10 dogs exposed to pacing of 240 beats/min for 3 to 4 weeks and eight sham
      operated controls. Na,K-ATPase was quantified using vanadate facilitated 3H
      ouabain binding to intact samples. At time of sacrifice paced dogs showed
      clinical signs of heart failure, a significant 257% increase in left ventricular
      end diastolic pressure and a significant 46% decrease in left ventricular dP/dt
      compared with control. There was no significant change in left ventricular mass.
      3H-ouabain binding concentration was significantly reduced by 16%. Evaluation of
      3H-ouabain binding kinetics revealed no significant difference between myocardium
      from paced and control dogs: Equilibrium binding conditions were at the various
      concentrations used obtained after similar incubation time; nonspecific uptake
      and retention of 3H-ouabain was 0.9-0.8% of total uptake and retention obtained
      in the standard assay; apparent dissociation constant (KD) was 6.5 x 10(-8)-6.6 x
      10(-8) mol/l; loss of specifically bound 3H-ouabain during washout at 0 degrees C
      occurred with a half-life time (T1/2) of 120 and 121 h. Hence, total 3H-ouabain
      binding site concentration in left ventricular myocardium was (mean +/- SEM) 1110
      +/- 56 and 1317 +/- 68 pmol/g wet weight, 8.54 +/- 0.43 and 10.05 +/- 0.52
      pmol/mg protein, and the total amount of 3H-ouabain binding sites in the entire
      left ventricle 121 +/- 6 and 162 +/- 8 nmol in paced (n = 10) and control (n = 8)
      dogs (p < 0.05), respectively. In conclusion, the present study reports a
      significant reduction in left ventricular myocardium 3H-ouabain binding site
      concentration in tachycardia induced heart failure. This observation supports the
      concept of a relationship between Na,K-ATPase concentration and contractile
      capacity and may be of pathophysiological importance in tachycardia and heart
      failure.

PMID- 8147828
TI  - Do the cardiac nerves optimise efficiency?
AB  - The cardiac nerves were removed by surgical dissection in anaesthetised dogs. At
      least 3 weeks were then allowed to elapse to permit degeneration of post
      ganglionic sympathetic nerve fibres and myocardial catecholamines. We then
      established that: 1) Myocardial oxygen consumption was increased for a given work
      output, indicating metabolic inefficiency; 2) glucose oxidation was inhibited; 3)
      uncoupled oxygen consumption of isolated myocardial tissue was increased, and 4)
      sodium-potassium ATPase activity was enhanced. These results are compatible with
      the hypothesis that the cardiac nerves optimise efficiency. There is some
      evidence from cardiac transplantation studies in man that a similar effect of
      innervation on efficiency is present. However, examination of this concept as a
      postulated result of evolutionary pressure led us to reject such a hypothesis (at
      least in man) because such a mechanism should be irrelevant to the factors
      determining survival at the time of human evolution. However, the hypothesis may
      be tenable for the situation at some earlier evolutionary era. This could be
      determined, in theory, by a comparative study between species of the effect of
      cardiac innervation upon efficiency.

PMID- 8147826
TI  - Effect of changes in aortic pressure and in coronary arterial pressure on left
      ventricular geometry and function Anrep vs. gardenhose effect.
AB  - Sudden increases in aortic pressure (AoP, mm Hg) are associated with increases in
      left ventricular (LV) function which persist even after diastolic volume has
      returned to its initial value (Anrep effect). Likewise, increases in coronary
      arterial pressure (CAP, mm Hg) are associated with improved LV function
      (gardenhouse effect). In situ, increases in AoP are paralleled by increases in
      both CAP and coronary blood flow, i.e., oxygen supply. We investigated the
      individual contributions of AoP and CAP increases on function (peak systolic
      pressure: LVPmax, mm Hg; dP/dtmax, mm Hg/s; end-diastolic pressure: LVPed, mm Hg)
      and end-diastolic geometry (inner diameter: IDed, mm; wall thickness: WTed, mm;
      sonomicrometry). CAP-induced increases in coronary flow were prevented by
      admixing dextran to the perfusate. The experiments were performed on isolated,
      saline-perfused, working rabbit hearts. Increasing CAP from 60 to 80 mm Hg (n =
      11) resulted in improved function: LVPmax 89 +/- 3 vs. 94 +/- 3, dP/dtmax 1160 +/
      50 vs. 1250 +/- 50, LVPed 17 +/- 1 vs. 16 +/- 1 (mean +/- SEM). IDed decreased
      from 9.96 +/- 0.25 to 9.64 +/- 0.33 and WTed increased from 6.02 +/- 0.16 to 6.15
      +/- 0.17. In a second series, AoP was increased from 60 to 80 (n = 9). Both
      LVPmax, dP/dtmax and LVPed increased (90 +/- 4 vs. 97 +/- 3, 1170 +/- 70 vs. 1270
      +/- 90 and 18 +/- 1 vs. 19 +/- 1). IDed increased from 9.76 +/- 0.39 to 9.99 +/-
      0.37 and WTed decreased from 6.08 +/- 0.22 to 5.86 +/- 0.25. After additionally
      increasing CAP to 80, function further improved (LVPmax: 101 +/- 3, dP/dtmax:
      1310 +/- 80) while LVPed decreased (18 +/- 1). This time, IDed decreased to 9.71
      +/- 0.36 and WTed increased to 6.03 +/- 0.26. Increases in CAP improve LV
      function via the gardenhose effect and likely do not depend on simultaneous
      increases in coronary flow or oxygen supply. On the other hand, increases in AoP
      alone improve systolic function via the Frank-Starling mechanism. Increases in
      both pressures together amplify this effect. Increases in CAP and in AoP have
      opposing effects on IDed and WTed. In conclusion, the homeometric Anrep effect-
      at least in part--can be viewed as synergistic action of the Frank-Starling
      mechanism and the gardenhose effect for this experimental model.

PMID- 8147829
TI  - Myocardial adaptations in advanced age.
AB  - Arterial stiffening and an increase in arterial pressure, particularly systolic,
      occur with advancing age in humans. The heart manifests left ventricular wall
      thickening and myocardial cell enlargement, which may be adaptations to these
      arterial changes. At the cellular level, studies in animal models indicate that
      the excitation-contraction coupling cycle is prolonged with aging. Specifically,
      a prolonged cystolic calcium transient enables prolonged force bearing capacity,
      an adaption permitting normal ejection of blood by the older heart into a stiff
      arterial tree. The changes in cellular Ca2+ cycling are regulated, in part at
      least, at the transcriptional level. Specifically, the density of Ca2+ pump sites
      of the sarcoplasmic reticulum is reduced, due to a down regulation of the gene
      coding for the sarcoplasmic reticulum Ca2+ pump, resulting in slower Ca2+ removal
      from the cytosole following excitation. During stress, a diminution in the
      increased heart rate and myocardial contractility occurs in healthy older humans,
      due in large measure to a postsynaptic reduction in the efficacy of beta
      adrenergic stimulation. At the cellular level in animal models, this is manifest
      by a relative failure of beta 1 adrenergic receptor stimulation to augment Ca2+
      influx via L-type sarcolemmal Ca2+ channels and to augment the amplitude of the
      cytosolic Ca2+ transient. However, in situ a cardiac adaptation, i.e., cardiac
      dilatation, occurs during stress and maintains the stroke volume of the older
      heart. The above cardiovascular adaptations that occur in older healthy humans
      and animals occur at a younger age in the presence of chronic pressure overload.

PMID- 8147830
TI  - Concepts of optimality and efficiency in biology and medicine from the viewpoint
      of philosophy of science.
AB  - If everything happens strictly according to the natural laws, which meet extremum
      principles, in what way can the possibility for life be characterised, so that
      the optimization processes of evolution can take place? Is it legitimate to
      "enlarge" the natural laws by certain laws of conservation? The question then
      arises of which are the new conservation quantities that are introduced by life
      itself? The concept of genidentity, which must not be confused with the
      biological concept of genes, is introduced and used to characterise the interface
      between animate and inanimate systems by the principle of conservation of
      genidentity. It thus becomes clear that animate systems can differ in the way and
      in how reliably they achieve their goal of self-preservation. The abundance of
      possibilities to be or not to be able to reach this goal offers the necessary
      scope in which the notion of a postulated assumed optimization in the theory of
      evolution is conceivable. The conservation principle of genidentical systems
      creates the possibility of evolutionary optimization by ranking these systems. An
      optimal lifespan of an individual genidentical system refers to the conservation
      principle of genidentical systems on a second supra-individual level (species).
      The optimization of the growth of a species needs the conservation of a
      genidentical system on a third level (symbiotic systems). The ranking of
      genidentical systems onto ever higher levels--so that the higher conservation
      principles always impose restrictions on the ones below--would come to an end
      when the minimization of raw materials and energy consumption limits all possible
      and available resources. Since the spectrum extending between opposite goals lies
      within the range of possible means of optimization, supposedly evolutionary goals
      of optimization are always attributed to nature by the observer.

PMID- 8147831
TI  - Beyond maximizing: some remarks on optimality and efficiency in the social
      sciences.
AB  - The author is dealing with the concept of homo oeconomicus and its relationships
      to maximizing, satisficing and optimizing practices, from the viewpoint of social
      sciences. Whereas in physics extremality-principles hold sway, in human affairs
      the "best" goals and courses of action usually lie between minima and maxima. In
      this context, attention is given to the fact that the exploding costs of the
      health system in western welfare states make it necessary to consider more
      thoroughly the double-maximization of the measures and of the goals of care.
      Nevertheless, the ideal typification of homo oeconomicus is useful to the
      classification and, sometimes, even to the explanation of those goal-oriented
      activities, where only limited resources are at hand.

PMID- 8147832
TI  - Efficiency of energy conversion from metabolic substrates to ATP and mechanical
      and chemiosmotic energy.
AB  - The free energy available from substrate oxidation is a largely invariable figure
      in biological systems. The extent to which this energy is conserved in high
      energy intermediates appears to be optimized during evolution to high efficiency.
      Since energy transformation by enzymatic and transport processes take place
      largely with fixed stoichiometrics, high efficiency can only be achieved by
      adapting free energy levels rather than by adapting turnover (number of molecules
      synthesized/hydrolyzed, etc.) The relatively small steps (equivalent with high
      efficiency) in free energy of various metabolic steps implicitly mean that
      changes in free energy leading to abolition of these steps (e.g., reduction of
      free energy of ATP) abolish the driving force and interrupt the (net) reaction.
      However, in the myocardium under limited energy supply (hypoxia) various
      protective mechanisms appear to be involved which keep free energy levels high
      for surviving of the cell but for the cost of function (contraction). Those
      mechanisms might play a role in the phenomena of hibernating and stunning.

PMID- 8147833
TI  - Efficiency of cardiac muscle: thermodynamic and statistical mechanical
      considerations.
AB  - The efficiency of cardiac muscle can be easily defined using thermodynamics and
      statistical mechanics. While thermodynamic definitions allow absolute measures of
      efficiency in terms of work output and free energy input, they do not provide
      insights into the underlying contraction mechanisms. The construction of
      molecular kinetics models of muscle, such as the cross-bridge theory, in
      conjunction with the use of statistical mechanics provides a framework for the
      examination of efficiency. The expressions of efficiency derived in this manner
      will be thermodynamically consistent and can be compared to experimental
      measurements, thereby rendering insight into cardiac energetics.

PMID- 8147834
TI  - Optimization of myocardial function.
AB  - Under normal conditions the cardiac output is designed to meet the metabolic
      needs of the organism. Thus, the demands imposed on the heart muscle can range
      from low values at rest to an order of magnitude greater values during exercise.
      The heart uses a number of strategies to meet the short- and long-term changes in
      demand. These strategies are of general biological interest and employ similar
      mechanisms to those responsible for the differences in muscle performance seen
      between muscle from various species and diverse muscle types within a given
      animal. This review deals with the heart's utilization of these strategies to
      meet a broad range of requirements. Tortoise (TM) and rat soleus (RS) muscles are
      slow, have high economy and develop low power. In contrast (FM) and rat extensor
      digitorum longus (REDL) are fast, have low economy and have a high power output.
      These differences are explainable in terms of the characteristics of the myosin
      head cross-bridge cycle (Cross-bridge tension-time integral: FM/FT = 0.024;
      REDL/RS = 0.16. Myosin ATPase activity: FM/TM = 15; RDEL/RS = 2.3) and excitation
      contraction coupling system (time to peak tension: FM/TM = 0.2; REDL/RS = 0.4).
      Heart muscle employs similar strategies (cross-bridge cycle; excitation
      contraction coupling) to meet short (catecholamine) and long (hypertrophy
      secondary to pressure overload or thyrotoxicosis) term changes in demand. In the
      presence of catecholamine power is increased while economy is decreased. This
      difference between control (C) and isoproterenol treated hearts (I) is
      explainable in terms of the contractile and excitation contraction coupling
      systems (Cross-bridge tension-time integral: I/C = 0.4. Tension independent heat:
      I/C = 2.0. Tension independent heat rate: I/C = 2.5). A persistent increase in
      the demand on the heart results in myocardial hypertrophy that is associated with
      intracellular reorganization. Hyperthyroidism (T) and pressure overload (PO) were
      used to produce myocardial hypertrophy. In T hearts the economy is decreased
      while the power is increased; in PO hearts oppositely directed changes occur.
      These alterations are attributable to changes in the performance of the
      contractile and excitation contraction coupling systems (Cross-bridge force-time
      integral: T/C/PO = 0.5/1.0/2.6. Tension independent heat: T/C/PO = 1.4/1.0/0.4.
      Tension independent heat rate: T/C/PO = 1.4/1.0/0.3). Thus it is clear that in
      meeting changes in demand, the heart uses strategies comparable to those seen
      between species and muscle types within a given muscle.

PMID- 8147835
TI  - Ventricular perspective on efficiency.
AB  - The heart has many efficiencies of different definitions, of which mechanical
      work efficiency is the most popular and conventional. We have proposed a method
      to quantify the total mechanical energy generated by ventricular contraction.
      This energy can be quantified as a specific area called "systolic pressure-volume
      area" or "PVA" in the ventricular pressure-volume diagram. In the left ventricle
      of excised, cross-circulated dog heart preparations, we found a closely linear
      relation between PVA and oxygen consumption (VO2) under various loading
      conditions in a stable contractile state (Emax). An enhanced contractility was
      accompanied by an elevation of the load-independent VO2-PVA relation in a
      parallel manner, where the elevation was proportional to Emax. The slope of the
      VO2-PVA relation represents the "oxygen cost of mechanical energy (or PVA)" and
      its reciprocal indicates the "contractile efficiency", i.e., the energy
      conversion efficiency from PVA-dependent VO2 to PVA. This efficiency was 40% on
      the average, independent of various inotropic interventions. The slope of the PVA
      independent VO2-Emax relation represents the "oxygen cost of contractility (or
      Emax)". This cost was relatively constant for different inotropic interventions
      except for myocardial cooling and stunning. We considered the discrepancy between
      the stable contractile efficiency and the variable thermal economy of force
      generation and maintenance.

PMID- 8147836
TI  - Geodesics as a mechanically optimal fiber geometry for the left ventricle.
AB  - Anatomical findings as well as theoretical considerations indicate that the
      myocardial fibers lie along minimal length geodesics of the left ventricular
      wall. Based upon this knowledge it is shown that the energy spent by the actively
      contracting fibers during systole, as well as the passive fiber stresses
      developed through diastole, are minimal in comparison with any other possible
      fiber configuration. Subsequently, it is concluded that for a given succession of
      left ventricular states, fiber shortening course and hence the amount of
      mechanical work are uniquely determined. Comparison with experimental findings
      concerning global left ventricular systolic work indicates that a given course of
      afterload produces a unique course of ventricular volume and of mechanical work.

PMID- 8147837
TI  - Philosophical aspects of defining efficiency for biological systems--an
      introductory overview.
AB  - This article introduces six themes that are in active discussion in contemporary
      philosophy of science. The first theme deals with definitions in general and
      their role in cardiology in particular. The second theme is on the structure of
      theory in cardiology. Third, the relationship between theory and experiment is
      examined, and then, fourthly, the nature of reduction and the relationship
      between concepts of lower levels and the concepts of higher levels in cardiology
      is considered. A closely related fifth theme deals with "co-evolution", where
      progress in cardiology is traced at mutually interactive levels of organization.
      Finally, I discuss the relationship of evolution and the optimization of cardiac
      function.

PMID- 8147838
TI  - Optimal coupling of the left ventricle with the arterial system.
AB  - In the human the heart contracts more than 2.0 billion times during the lifetime.
      The total amount of energy required in this period is equivalent to lift a huge
      tanker (more than 200 thousand tons) above your head. Thus there is no question
      that the heart requires a huge amount of energy. Since minimization of energy
      requirements would be one of the major design goals of the cardiovascular system,
      we investigated energy efficiency of ventriculo-arterial coupling under various
      conditions. In normal conscious dogs, the arterial system extracted maximal work
      from the left ventricle during exercise as well as at rest. At the same time, the
      energy consumption of the left ventricle to support the peripheral demand was
      minimum. This optimal coupling condition was well maintained despite changes in
      blood volume. The baroreflex system appeared to play a crucial role in this
      optimization. In the presence of left ventricular dysfunction, however, this
      optimality was no longer maintained. We conclude that the efficiency of cardiac
      contraction is fairly well maintained under various stresses as long as left
      ventricular function is normal.

PMID- 8147839
TI  - Myocardial adaptation to stress from the viewpoint of adaptation and development.
AB  - Myocardial adaptation to stress and development includes reorganization of
      subcellular systems. Using a myothermal method, changes in the contractile
      protein system were investigated across species (rat, rabbit, human myocardium)
      and in consequence of hemodynamic (volume overload human, pressure overload
      rabbit myocardium) or hormonal stresses (hypothyroid rat, hyperthyroid rabbit
      myocardium). Mechanical and myothermal measurements were performed in
      isometrically contracting right or left ventricular muscle strips and the force
      time integral of the individual crossbridge cycle was calculated from heat and
      force data. Within species, crossbridge force-time integral increased by 85% from
      control human to volume overload human myocardium. Crossbridge force-time
      integral increased by 100% from control to hypothyroid rat myocardium. In rabbit
      myocardium, crossbridge force-time integral increased by 164% in pressure
      overload and decreased by 47% in hyperthyroid compared to control myocardium.
      Across species, crossbridge force-time integral was smallest in control rat
      myocardium (0.16 +/- 0.01 pNs) and increased in the order: control rat <
      hyperthyroid rabbit < hypothyroid rat, control rabbit < control human < pressure
      overload rabbit < volume overload human myocardium (0.96 +/- 0.01 pNs). Within
      and across species, crossbridge force-time integral was positively correlated
      with time to peak tension (r = 0.86; p < 0.05) and negatively correlated with
      maximum rate of tension rise (r = -0.85; p < 0.05) and maximum rate of tension
      fall (r = -0.78; p < 0.05). Furthermore, there were significant correlations
      between crossbridge force-time integral and total activity related heat (r = 
      0.81; p < 0.05) as well as total activity related heat per tension-time integral
      (r = -0.89; p < 0.005). Thus, the close relationship between crossbridge force
      time integral and myocardial function within and across species demonstrates that
      alterations of crossbridge force-time integral reflect an important mechanism of
      subcellular adaptation to stress from a mechanical point of view. Moreover,
      alterations of the crossbridge force-time integral have pronounced effects on
      energy consumption in the different types of myocardium.

PMID- 8147840
TI  - Molecular perspectives of chromosome pairing at meiosis.
AB  - Ideas about the mechanisms that regulate chromosome pairing, recombination, and
      segregation during meiosis have gained in molecular detail over the last few
      years. The purpose of this article is to survey briefly the shifts in paradigms
      and experiments that have generated new perspectives. It has never been very
      clear what it is that brings together the homologous chromosomes at meiotic
      prophase. For a while it appeared that the synaptonemal complex might be the
      nuclear organelle responsible for synapsis, but the supporting evidence has not
      been entirely convincing. Whatever the mechanism, it has always been assumed that
      homologous synapsis creates the opportunity for homologous DNA sequences to
      initiate recombination. At present, alternative ideas are developing. Attractive
      is the concept that double strand DNA repair mechanisms, that find and use the
      undamaged homologue for repair, have evolved into a meiotic mechanism for the
      recognition and pairing of homologous sequences. Subsequent intimate synapsis of
      homologous chromosomes in the context of the synaptonemal complex may serve later
      functions in the regulation of interference and segregation at first anaphase. A
      number of areas that are being tested at present and some that may be
      investigated in the future are discussed at the end of the review.

PMID- 8147841
TI  - How meiotic cells deal with non-exchange chromosomes.
AB  - The chromosomes which segregate in anaphase I of meiosis are usually physically
      bound together through chiasmata. This association is necessary for proper
      segregation, since univalents sort independently from one another in the first
      meiotic division and this frequently leads to genetically unbalanced offspring.
      There are, however, a number of species where genetic exchanges in the form of
      meiotic cross-overs, the prerequisite of the formation of chiasmata, are
      routinely missing in one sex or between specific chromosomes. These species
      nevertheless manage to segregate these non-exchange chromosomes. There are four
      direct modes for associating achiasmatic chromosomes: (a) modified SC, (b)
      adhesion of chromatids comparable to somatic pairing, (c) 'stickiness' of
      heterochromatin or (d) specific 'segregation bodies', consisting of material
      structurally different from chromatin. There is also the possibility that the
      spindle-possibly joining forces with the kinetochores--carries out the faithful
      segregation of univalents which are not directly physically attached to one
      another. Finally, amphitelic orientation of univalents in metaphase I and pairing
      of the chromatids in meiosis II appear to ensure correct segregation as well.

PMID- 8147842
TI  - alpha/beta barrel evolution and the modular assembly of enzymes: emerging trends
      in the flavin oxidase/dehydrogenase family.
AB  - Alpha/beta barrels have an ill-defined origin. Evidence exists which favours
      their divergent evolution from a common ancestral barrel and convergent evolution
      to a stable fold. However, recent sequence and structural information for the
      flavin oxidase/dehydrogenase family of barrel enzymes indicate that sub-families
      of alpha/beta barrels have evolved divergently. The modular fusion of barrel
      domains with core structures from other gene families has also contributed to the
      evolution of related but catalytically distinct enzyme molecules within each sub
      family of the flavin oxidases/dehydrogenases. An analysis of the structures and
      sequences of the flavin oxidases/dehydrogenases has now enabled studies focusing
      on the evolutionary origins and modular assembly of this important family of
      proteins to be initiated.

PMID- 8147843
TI  - Growth factors as survival factors: regulation of apoptosis.
AB  - Apoptosis is now widely recognized as a common form of cell death and represents
      a mechanism of cell clearance in many physiological situations where deletion of
      cells is required. Peptide growth factors, initially characterised as stimulators
      of cell proliferation, have now been shown to inhibit death in many cell types.
      Deprivation of growth factors leads to the induction of apoptosis, i.e.
      condensation of chromatin and degradation in oligonucleosome-sized fragments,
      formation of plasma and nuclear membrane blebs and cell fragmentation into
      apoptotic bodies which can be taken up by neighbouring cells. Here we discuss the
      mechanism(s) by which growth factors may inhibit apoptosis.

PMID- 8147844
TI  - Some genes were isolated and their structure studied before the recombinant DNA
      era.

PMID- 8147845
TI  - Atherosclerosis and glycation.
AB  - Atherosclerosis is the major cause of death in the industrialised world. Though
      much work on the pathogenesis of atherosclerosis points to 'oxidised' low density
      lipoprotein (LDL) as a key aetiological feature in the generation of the
      atherosclerotic plaque, the nature of this 'oxidised' LDL in vivo remains an
      enigma. We argue here that glycated LDL shows many of the characteristics
      attributed to 'oxidised LDL' and may be the source of the latter in vivo. These
      include the increased uptake and impaired degradation of glycated LDL by
      macrophages and the stimulation of transendothelial chemotaxis of monocytes,
      cytokine secretion and platelet aggregation. We hypothesise that the covalent
      binding of glycated LDL to the endothelial cell wall may result in the formation
      of the early atherosclerotic lesion of the fatty streak and that apolipoprotein E
      may mediate the physiological clearance of glycated moieties. The proposed role
      of glycation in the pathogenesis of atherosclerosis would explain its high
      incidence among diabetics and the contentious epidemiological and experimental
      correlations between dietary sugar and atherosclerosis.

PMID- 8147846
TI  - The evolution of heteromorphic sex chromosomes.

PMID- 8147847
TI  - A mouse model for human hereditary tyrosinemia I.

PMID- 8147848
TI  - H19, a tumour suppressing RNA?

PMID- 8147849
TI  - Protein tracking-induced supercoiling of DNA: a tool to regulate DNA transactions
      in vivo?
AB  - An interplay between DNA-dependent biological processes appears to be crucial for
      cell viability. At the molecular level, this interplay relies heavily on the
      communication between DNA-bound proteins, which can be facilitated and controlled
      by the dynamic structure of double-stranded DNA. Hence, DNA structural
      alterations are recognized as potential tools to transfer biological information
      over some distance within a genome. Until recently, however, direct evidence for
      DNA structural information as a mediator between cellular processes was lacking.
      This changed when the concept of transient waves of DNA supercoiling, induced by
      proteins tracking along the right-handed DNA double helix, came into the
      limelight. Indeed, a number of observations now suggest that helix tracking
      induced DNA structural information might be exploited to participate in the
      regulation of a variety of DNA transactions in vivo.

PMID- 8147850
TI  - Calcium-dependent proteinase activity in root cultures of Arabidopsis.
AB  - The presence of calcium-dependent proteinase in plants was investigated using
      soluble proteins from Arabidopsis root cultures. Calcium increased the
      proteolytic activity by two to three fold. Calcium-stimulated proteolytic
      activity was inhibited by different protease inhibitors. The highest inhibition
      (79%) of calcium-dependent proteolytic activity was observed in the presence of
      leupeptin. Thirty-eight percent of calcium-dependent proteolytic activity was
      inhibited by E-64, an inhibitor of cysteine proteinases. Calmodulin did not have
      any effect on calcium-dependent as well as calcium-independent proteolytic
      activity in the cellular extract. These results provide the first evidence for
      the presence of calcium activated proteinase in plants and open new avenues to
      investigate the mode of calcium action in plants.

PMID- 8147851
TI  - Cloning and sequencing of phenylethylamine oxidase from Arthrobacter globiformis
      and implication of Tyr-382 as the precursor to its covalently bound quinone
      cofactor.
AB  - The gene of Arthrobacter globiformis encoding a quinoprotein, phenylethylamine
      oxidase, has been cloned and sequenced. In the deduced amino acid sequence
      comprising 638 residues is a tetrapeptide sequence, Asn-Tyr-Asp-Tyr, which has
      been found to be highly conserved in other copper amine oxidase. Mutation of the
      former Tyr (Tyr-382) of the recombinant enzyme into Phe resulted in the complete
      loss of catalytic activity and disappearance of the quinone compound that is
      specifically detected in the wild-type enzyme, suggesting that Tyr-382 is the
      precursor to the covalently-bound cofactor, most probably topa quinone.
      Furthermore, the expression of the active, quinone-containing enzyme in
      Escherichia coli cells was markedly dependent on the presence of Cu2+ ions in the
      culture medium, and the inactive, Cu2(+)-deficient enzyme produced without Cu2+
      ions could be converted to the active quinone form by reconstitution with Cu2+
      ions.

PMID- 8147852
TI  - Regulation of calcium channel in sarcoplasmic reticulum by calsequestrin.
AB  - Gating properties of the Ca2+ channel in sarcoplasmic reticulum (SR) were
      monitored by measuring the choline permeation of the heavy fraction of SR (HSR)
      vesicles by the light scattering method. Increase of choline permeation by
      micromolar Ca2+, which refers to Ca2+ response, was lost when HSR vesicles were
      incubated overnight with EDTA or EGTA. In parallel, calsequestrin was released
      from the vesicles. This loss of Ca2+ response could not be inhibited by
      millimolar Mg2+, but was partially inhibited by submolar KCl. Since it took 3-5
      hours to lose the Ca2+ response, calsequestrin may be released from the inside of
      the vesicles. When HSR vesicles were incorporated into lipid bilayer, open
      probability of the Ca2+ channel increased when calsequestrin was added to the
      trans side in the presence of millimolar Ca2+. These results suggest that
      calsequestrin acts as a regulator of Ca2+ channel in SR membrane.

PMID- 8147853
TI  - IP3-activated calcium-permeable channels in the inside-out patches of cultured
      cerebellar Purkinje cells.
AB  - Inositol-1,4,5-trisphosphate (IP3)-activated calcium-permeable channels were
      recorded from inside-out patches of cultured cerebellar Purkinje cells. When 2-5
      microM of IP3 was applied to the internal surface of the inside-out patches,
      inward Ba2+ currents were activated within 10 sec following the application in 11
      out of 24 patches. In the presence of heparin (100 micrograms/ml), activation of
      Ba2+ currents by IP3 was inhibited. Unitary currents with different amplitudes
      and kinetics were observed; small and large unitary currents, and rapid
      fluctuations with various amplitudes. The small unitary currents (single channel
      conductance; 5.6 pS) were most frequent. Addition of inositol 1,3,4-trisphosphate
      (2-5 microM) slightly activated Ba2+ currents in 2 out of 10 patches, but the
      amount of the increment was much smaller than that produced by IP3. These results
      suggest a possibility that IP3 directly activates Ca(2+)-permeable channels in
      the plasma membrane of cerebellar Purkinje cells.

PMID- 8147854
TI  - Structure and expression of two plant genes encoding chromoplast-specific
      proteins: occurrence of partially spliced transcripts.
AB  - The genes encoding fibrillin and capsanthin-capsorubin synthase are specifically
      expressed during fruit ripening in Capsicum annuum, leading to the accumulation
      of these two proteins in chromoplasts. Here, we report for the first time the
      cloning of genomic DNA fragments encoding these two enzymes, as well as DNA
      fragments containing upstream regions which are potentially involved in the
      regulation of the expression of these genes. While the capsanthin-capsorubin
      synthase gene is uninterrupted, the fibrillin gene is interrupted by two introns,
      the first one being inefficiently spliced. Occurrence of unspliced transcripts is
      apparently not related to a post-transcriptional mechanism controlling the
      synthesis of fibrillin or an alternative polypeptide. This work provides tools
      for studies on gene activation and intron splicing in plants.

PMID- 8147855
TI  - Insulin and lipogenesis in rat adipocytes. II. Effect of high levels of insulin
      and glucose on lipid synthesis in isolated rat adipocytes.
AB  - Insulin resistant states are characterized by receptor and post-receptor defects
      in insulin action. When the insulin resistant state progresses, elevated levels
      of insulin are accompanied by increasing levels of glucose. In a previous paper
      we demonstrated that treatment of isolated adipocytes with high levels of insulin
      led to a decrease in insulin binding as well as a decrease in basal and insulin
      stimulated lipid synthesis. The results of the present study establish that the
      addition of high concentrations of glucose in combination with a high level of
      insulin, does not modify the decrease in binding of insulin to its receptor.
      However, the decrease in lipid synthesis previously observed in the presence of
      high concentrations of insulin was completely overcome by the presence of high
      glucose.

PMID- 8147856
TI  - Effects of sialic acid and sialoglycoconjugates on cytosolic phospholipases A2
      from bovine brain.
AB  - Two forms of Ca(2+)-independent cytosolic phospholipases A2 were separated by
      Sephadex G-75 column chromatography. N-Acetylneuraminic acid, gangliosides, and
      sialoglycoproteins inhibited both phospholipases A2 in a concentration dependent
      manner, but colominic acid, poly(2,8-N-acetylneuraminic acid), had no effect on
      enzymic activities. Interactions between phospholipases A2 and
      sialoglycoconjugates may be involved in the translocation of phospholipases A2
      from cytosol to plasma membrane during receptor stimulation.

PMID- 8147857
TI  - 2-Aminopurine overrides a late telophase delay created by ectopic expression of
      the PITSLRE beta 1 protein kinase.
AB  - Minimal overexpression of the PITSLRE beta 1 protein kinase in CHO cells leads to
      a marked delay in late mitosis. We have previously shown that this delay is
      characterized by the presence of substantially increased numbers of tubulin
      midbodies, inhibition of cytokinesis, and numerous multinucleated and
      micronucleated cells. Others have shown that the protein kinase inhibitor 2
      aminopurine (2-AP) is capable of overriding drug induced cell cycle blocks. In
      this study we demonstrate that the late mitotic delay and altered cellular
      morphology caused by ectopic expression of the PITSLRE beta 1 protein kinase can
      be overcome by 2-aminopurine treatment. Furthermore, 2-aminopurine inhibits
      PITSLRE beta 1 protein kinase activity in vivo, but does not effect p34cdc2
      protein kinase activity in a similar manner.

PMID- 8147858
TI  - A soluble neurite outgrowth molecule in bovine brain.
AB  - A neurite outgrowth molecule was purified from soluble fraction of bovine brain
      by reversed-phase column HPLC following concanavalin A (Con A)-affinity
      chromatography. This molecule was a 74kDa (named sGP74) and clearly reacted with
      the monoclonal antibody HNK-1. The amino acid sequences of N-terminal portion and
      peptides derived from trypsin digests of sGP74 were nearly identical to those of
      rat brain ankyrin-binding protein (ABGP186) that is a member of immunoglobulin
      superfamily with adhesive function. Our results suggest that sGP74 preserves
      multiple immunoglobulin-like domains and is released from an extracellular site
      of ABGP186.

PMID- 8147859
TI  - Role of plasma membrane ganglioside sialidase of human neuroblastoma cells in
      growth control and differentiation.
AB  - In cultured human neuroblastoma cells (SK-N-MC), a plasma membrane-bound besides
      a lysosomal ganglioside GM3 sialidase was detected. Both activities can be
      distinguished by the specific activation with detergents, as well as differential
      inhibition by Cu++. Plasma membrane and lysosomal sialidase specific activities
      showed strikingly different behaviour during the growth phase of neuroblastoma
      cells. Thus, the plasma membrane sialidase increased about 15-fold and mirrored
      cell growth, it differed from the kinetics of ornithine decarboxylase, an early
      marker of cell proliferation. The lysosomal sialidase, on the other hand,
      exhibited constant specific activities during growth of the cells, as did
      lysosomal and plasma membrane marker enzymes. When the sialidase inhibitor 2,3
      dehydro-2-deoxy-N-acetylneuraminic acid was included in the culture medium, a
      profound change in proliferation kinetics was observed, indicating a release from
      density-dependent control of cell division. Additionally, the inhibitor abolished
      the increase of the biochemical differentiation marker acetylcholinesterase. The
      results suggest an important role of the ganglioside sialidase of the plasma
      membrane in the processes of proliferation control and differentiation in this
      neuronal cell system.

PMID- 8147860
TI  - Detection of Choristoneura fumiferana brush border membrane-binding molecules
      specific to Bacillus thuringiensis delta-endotoxin by crossed affinity
      immunoelectrophoresis.
AB  - Brush border membrane vesicles (BBMVs) prepared from midguts of Choristoneura
      fumiferana larvae were pretreated separately with the three CryIA delta
      endotoxins from Bacillus thuringiensis subsp. kurstaki HD-1. Crossed affinity
      immunoelectrophoresis of the solubilized toxin-BBMV complexes, using antibodies
      raised against the toxins, revealed at least two peaks for each toxin. All
      complexes (BBMV bound toxin) migrated in the opposite direction to that of the
      free toxins. It is concluded that the toxins form stable complexes with membrane
      acceptor molecules, possibly receptors, and that there are at least two types of
      acceptor molecules present in the midgut epithelial cells of C. fumiferana that
      bind to all three toxins. The relative size of one of the BBMV-toxin peaks
      correlates with the in vivo potency of the toxins against C. fumiferana.

PMID- 8147861
TI  - Inhibition of isoprenoid biosynthesis induces apoptosis in human promyelocytic HL
      60 cells.
AB  - Protein isoprenylation is a posttranslational modification that facilitates
      membrane association and biological activity of a number of proteins. Mevalonate
      is the precursor of cellular sterols as well as of isoprenoid lipids involved in
      protein modification. In this study we show that HL-60 cells treated with
      lovastatin, an inhibitor of mevalonate synthesis, exhibit alterations in growth
      and morphology, as well as changes in the subcellular distribution of
      isoprenylated proteins like nuclear lamin A and p21Ras. Moreover, they are
      induced to die via apoptosis, as evidenced by the appearance of a typical DNA
      fragmentation pattern. Lovastatin-induced DNA fragmentation can be specifically
      prevented by mevalonate. The failure of several products of the mevalonate
      pathway, including cholesterol, to overcome lovastatin effect, points to the
      involvement of isoprenylated proteins in the mechanisms suppressing cell death.

PMID- 8147863
TI  - Stereochemical course of hydrolysis catalysed by Cellulomonas fimi CenE, a member
      of a new family of beta-1,4-glucanases.
AB  - The gene for a previously identified, extracellular, 120 kDa cellulose-binding
      protein (Cbp120) was isolated from a Cellulomonas fimi genomic library and
      expressed in Escherichia coli. Qualitative analysis of CM-cellulose hydrolysis
      shows that Cbp120 is an endo-beta-1,4-glucanase. Cbp120, now renamed CenE,
      catalyzes hydrolysis of cellohexaose with inversion of anomeric carbon
      configuration, characteristic of a single displacement reaction. Partial
      sequencing of its gene shows that CenE has significant sequence similarity with
      the catalytic domains of five enzymes from cellulolytic bacteria. It is proposed
      that the six enzymes form a new family of beta-1,4-glucanases. CenE is the first
      enzyme from this family to be characterized stereochemically.

PMID- 8147862
TI  - Protein kinase C is crucial for the stimulation of sodium-dependent phosphate
      transport by parathyroid hormone-related peptide in osteoblast-like cells.
AB  - In the present study, we investigated the role of parathyroid hormone-related
      peptide (PTHrP)-responsive dual signal transduction systems in the regulation of
      sodium-dependent phosphate (Pi) transport by PTHrP in UMR-106 cells. Exposure of
      the cells to 10(-7) M human (h) PTHrP-(1-34) induced a significant increase in Pi
      uptake within 15 min of incubation. The peptide stimulated Pi uptake dose
      dependently at the range of 10(-11)-10(-7) M. Activation of protein kinase C
      (PKC) by 12-O-Tetradecanoyl phorbol-13-acetate (TPA) also increased Pi uptake in
      time- and dose-dependent manners similar to PTHrP. In contrast, neither
      activation of adenylate cyclase by 10(-5) M forskolin nor calcium ionophore
      treatment with 10(-7) M A23187 affect Pi uptake. These agents failed to influence
      on Pi uptake even in combined treatment with TPA. The PTHrP-induced increase in
      Pi uptake was strongly inhibited by pretreating cells with PKC inhibitors, 1-(5
      isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 microM), and
      by down-regulating PKC with a prolonged TPA pretreatment. These results indicate
      that the messenger system mediated by PKC, rather than adenylate cyclase or
      cytosolic calcium, plays a crucial role in the regulation of sodium-dependent Pi
      transport by PTHrP in the osteoblast-like cells.

PMID- 8147864
TI  - Purification of gonadotropin surge-inhibiting factor from Sertoli cell-enriched
      culture medium.
AB  - Gonadotropin surge-inhibiting factor (GnSIF) is a novel biological factor in
      follicular fluid that inhibits the pre-ovulatory LH and FSH surges. Recent
      studies suggest that the biological activity of GnSIF can be attributed to
      inhibin. Preliminary studies showed that the Sertoli cell-conditioned medium
      contains GnSIF-like biological activity. Using 32 liters of primary Sertoli cell
      enriched culture medium and an in vitro pituitary bioassay, GnSIF was isolated.
      GnSIF is a single monomeric polypeptide (Mr of 37,000) with a partial N-terminal
      amino acid sequence of NH2-SDXXPQL which is distinct from any existing protein
      sequences. The identity of the inhibin that was separated from GnSIF was
      confirmed by direct protein sequencing. The purified GnSIF inhibited GnRH
      stimulated LH- and basal FSH-release from pituitary cells cultured in vitro dose
      dependently with a half maximal effective dose of about 1.4 ng/ml and 3.5 ng/ml,
      respectively. The half maximal effective dose of inhibin to suppress the
      pituitary GnRH-stimulated LH- and basal FSH-release was 2.5 ng/ml and 0.8 ng/ml,
      respectively. This study demonstrates that GnSIF is a unique protein that shares
      some biological activities with inhibin.

PMID- 8147865
TI  - Evidence that c-src is involved in the process of osteoclastic bone resorption.
AB  - Transgenic mice lacking a functional c-src gene have osteopetrosis, a bone
      disorder characterized by defective osteoclast function. We have investigated the
      effects of selective protein tyrosine kinase inhibitors that are known to inhibit
      c-src, on osteoclast activity in the bone slice assay. Geldanamycin, herbimycin A
      and monorden (0.001-10 microM) all dose-dependently inhibited bone resorption
      with IC50 values of 8, 70 and 86 nM, respectively. At concentrations of 0.001-1
      microM, the compounds were not cytotoxic as judged by osteoclast morphology and
      survival on bone slices. In order to determine whether c-src plays a role in
      signal transduction associated with osteoclast activation prior to bone
      resorption commencing, or in the resorptive process itself, we performed kinetic
      experiments using human calcitonin as a positive control. Calcitonin inhibited
      all bone resorption subsequent to its addition at t = 0, 3 or 6 hr (100%,
      approximately 90% and approximately 50% inhibition, respectively), after the
      start of the 24 hr bone slice assay. Similar results were obtained with
      herbimycin A and geldanamycin (1 microM) added at t = 0, 3 or 6 hr, and with
      monorden (1 microM) added at t = 0 and 6 hr. These results indicate that c-src
      plays a crucial and continuous role in the process of osteoclastic bone
      resorption, most likely related to the translocation and/or fusion of exocytic
      vesicles to the ruffled border membrane.

PMID- 8147866
TI  - Nitric oxide production by activated human neutrophils exposed to sodium azide
      and hydroxylamine: the role of oxygen radicals.
AB  - The occurrence of a nitric oxide-generating system in human neutrophils has been
      controversial and the detection of nitric oxide rendered more difficult due to
      the capacity of oxygen radicals and other compounds to scavenge this molecule.
      Our results demonstrate that human neutrophils, when stimulated by adherence or
      by phorbol myristate acetate generate nitrite upon exposure to NaN3 or
      hydroxylamine. NaN3-dependent nitrite production was further increased by the
      addition of superoxide dismutase (SOD). The generation of nitrite was also
      stimulated by exogenous added H202 in resting neutrophils and could be induced in
      a cell-free system containing heme-enzymes, H202 and NaN3, suggesting a
      requirement for H202-mediated oxidation of NaN3 in nitrite formation by the
      stimulated cells. Treatment of the neutrophils with hydroxylamine led to the
      production of even larger quantities of nitrite (> 25 nmol/h.10(6) cells), an
      effect that was prevented by SOD, pointing to superoxide as a metabolite possibly
      involved in nitrite formation. These results emphasize the importance of oxygen
      radicals or other intermediates in the generation of nitrite by stimulated
      neutrophils exposed to the above compounds.

PMID- 8147867
TI  - Cell death protection by 3-aminobenzamide: impairment of cytoskeleton function in
      human NK cell-mediated killing.
AB  - 3-aminobenzamide, an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase,
      is capable of interfering with the tumor cell lysis induced by specialized cells
      from the immune system, i.e., natural killer (NK) cells. In this report we
      suggest that the mechanism by which the drug can exert its protective effects on
      target cell killing by NK effectors can also be due to its ability to impair cell
      to-cell conjugate formation (binding), without affecting either the expression of
      cell adhesion molecules nor the features of effector-target cell contact. The
      mechanism of this inhibition seems to be associated with an alteration of
      cytoskeletal elements involved during conjugate formation, i.e., with the
      integrity and function of the microfilament system.

PMID- 8147868
TI  - Formylmethanofuran synthesis by formylmethanofuran dehydrogenase from
      Methanobacterium thermoautotrophicum Marburg.
AB  - Formylmethanofuran dehydrogenase was purified 30-fold from the cytosolic fraction
      of cell extract of Methanobacterium thermoautotrophicum (Marburg) and shown for
      the first time to synthesize in vitro formylmethanofuran from methanofuran and
      carbon dioxide with electrons donated by titanium(III) citrate. The reaction was
      methanofuran-, CO2-, and Ti(3+)-dependent. Active enzyme could be purified from
      cells grown with either molybdenum or tungsten as the sole group VIA trace
      element. The active form of formylmethanofuran dehydrogenase had an apparent
      molecular mass of 530 kDa as determined by gel filtration chromatography and was
      found to copurify with a hydrogenase.

PMID- 8147869
TI  - Thrombin receptor agonist peptide decreases thrombomodulin activity in cultured
      human umbilical vein endothelial cells.
AB  - Recently, it has been shown that the N-terminal peptide from a new type of
      thrombin receptor exhibits thrombin receptor agonist activity. We examined the
      effects of this synthetic thrombin receptor against peptide (SFLLRNPNDKYEPF,
      TRAP) on human umbilical vein endothelial cells (HUVECs). TRAP induced rapid
      morphological changes in HUVECs, with marked increase in the release of
      prostacyclin, endothelin, platelet activating factor, tissue type plasminogen
      activator, and plasminogen activator inhibitor-1. Incubation of cells with TRAP
      also induced a rapid decrease in cell-surface thrombomodulin. Thus, activation of
      the newly described thrombin receptor may alter their role in the hemostatic
      pathway.

PMID- 8147870
TI  - Nitric oxide toxicity in islet cells involves poly(ADP-ribose) polymerase
      activation and concomitant NAD+ depletion.
AB  - Previous studies have shown that DNA strand breaks are an early consequence of
      nitric oxide toxicity in pancreatic islet cells. We show here that exposure of
      islet cells to chemical NO donors causes the formation of ADP-ribose polymers in
      cell nuclei, with concomitant depletion of intracellular NAD+. Islet cell lysis
      was largely prevented by the ADP-ribosylation inhibitors nicotinamide, 3
      aminobenzamide, and 4-amino-1,8-naphthalimide, the latter being a potent new
      generation compound with high selectivity for poly(ADP-ribosyl)-ation. These
      findings indicate a key role of poly(ADP-ribose) polymerase activation in NO
      toxicity in islet cells.

PMID- 8147871
TI  - Kinetics of human apohemoglobin dimer dissociation.
AB  - Heme chain exchange was employed to investigate the dimer dissociation reaction
      of human apohemoglobin in 0.1 M potassium phosphate buffer, pH 7.0, at 20 degrees
      C. Incubation of apohemoglobin (alpha 0 beta 0) with either alpha h (or beta h)
      allowed the monitoring of the formation of a semihemoglobin alpha h beta 0 (or
      alpha 0 beta h) species with time. Analysis revealed that the rate of formation
      of both semihemoglobins was essentially identical and coincided with the
      disappearance of heme chain. Time courses were exponential and followed first
      order kinetics yielding a dimer dissociation rate constant of 0.54 (+/- 0.07) h
      1. A study over the pH range from 6.5 to 8.0 revealed that this dissociation rate
      exhibited a maximum at pH 7.0 (implicating a histidyl residue). The effect of
      temperature (6-37 degrees C) on this dimer dissociation rate yielded a linear
      Arrhenius Plot and an energy of activation of 7.2 kcal/mol. These results are
      consistent with alpha G-beta G helical pairing being a major contributor to
      apohemoglobin dimer integrity.

PMID- 8147872
TI  - Characterization of the dihemic cytochrome c549 from the marine denitrifying
      bacterium Pseudomonas nautica 617.
AB  - A dihemic ferricytochrome c549 (21 kDa) was purified and characterized from cells
      of the marine denitrifier Pseudomonas nautica strain 617. Several spectroscopic
      techniques, including UV-visible, NMR and EPR spectroscopies were applied to the
      characterization of this cytochrome. The visible and the 1H-NMR spectra show that
      both hemes have histidine-methionine as axial ligands. The dihemic cytochrome
      c549 has mid-point redox potentials of +230 mV and +250 mV, at pH 7.6 and its NH2
      terminal sequence presents a high degree of similarity with those of cytochromes
      c4. The EPR studies allowed the determination of the orientation between the two
      axial ligands, indicating an axial ligand field for one of the hemes of
      cytochrome c549 and a rhombic symmetry for the other heme.

PMID- 8147873
TI  - Complete amino acid sequence and comparative molecular modelling of HPr from
      Streptococcus mutans Ingbritt.
AB  - The heat-stable phosphocarrier protein (HPr) of Streptococcus mutans was
      extracted from whole cells using sodium lauroylsarcosinate/EDTA and purified to
      homogeneity by a single-step, ion-exchange chromatographic procedure. The
      complete amino acid sequence of the protein was determined from peptides
      generated by trypsin, alpha-chymotrypsin, endoproteinase Glu-C, and cyanogen
      bromide treatment. The HPr from S. mutans contains 86 or 87 amino acyl residues,
      depending on removal of the N-terminal Met and the protein shows high sequence
      homology with HPr from other Gram-positive bacteria. The predicted tertiary
      structure of the S. mutans HPr, from model building by homology, is an open-faced
      beta-sandwich consisting of two alpha-helices and a four-stranded antiparallel
      beta-sheet.

PMID- 8147874
TI  - Sodium channel subtypes in the rat display functional differences in the presence
      of veratridine.
AB  - The alkaloid neurotoxin veratridine has the unique property of functionally
      distinguishing sodium channel subtypes in the rat through differences in single
      channel conductances, channel substates and probability of channel opening.
      Veratridine-activated cardiac sodium channels from rat ventricular muscle
      displayed a single channel conductance of 8.4 pS with no evidence of
      subconductance states or channel subtypes. Rat skeletal muscle sodium channels
      displayed both high (8.5 pS) and low conductance (4.7 pS) openings as well as a
      lower probability of opening (approximately 50%) at depolarized potentials than
      shown with brain or cardiac sodium channels (90-95%). Rat brain veratridine
      activated sodium channels displayed primarily subconductance states at
      depolarized potentials (3-6 pS) and full conductance of approximately 9.5 pS at
      hyperpolarized potentials.

PMID- 8147875
TI  - Na(+)-dependent high-affinity uptake of choline into cultured fibroblasts.
AB  - The acetylcholine precursor choline is transported into cholinergic neurons by a
      high-affinity, sodium-dependent mechanism that is selectively localized to the
      cholinergic nerve terminal. In addition, a low-affinity, sodium-independent
      choline uptake system is present in cholinergic and non-cholinergic cells which
      deliver choline for cell membrane anabolism. Here, we show that uptake of
      [3H]choline into cultured fibroblast cell lines exhibits high affinity (Km < or =
      10 microM), is sodium-dependent, and is blocked by hemicholinium, a classical
      inhibitor of neuronal high-affinity choline uptake. Our data indicate that sodium
      dependent high-affinity choline transport systems are also present in non
      cholinergic cells.

PMID- 8147876
TI  - Modulation of calpastatin specificity in rat tissues by reversible
      phosphorylation and dephosphorylation.
AB  - Two calpastatins, with Mr 110 KD and named calpastatin I and II, have been
      isolated from rat heart and kidney and displayed distinct inhibitory efficiency
      with mu- and m-calpain, respectively, as those isolated from rat skeletal muscle.
      Whereas the level of calpastatin I always exceeds that of mu-calpain, the level
      of calpastatin II appears to be more closely correlated to the level of m
      calpain. As previously shown for skeletal muscle, the two inhibitor proteins can
      be interconverted by a phosphorylation-dephosphorylation reaction; the enzyme
      responsible for phosphate incorporation in calpastatin I is now identified in c
      AMP dependent protein kinase A. In rat erythrocytes, containing a single calpain
      form, the single low Mr calpastatin form does not undergo reversible
      phosphorylation and is equally efficient in respect to typical mu- and m-calpain.
      The presence of two interconvertible calpastatin forms provides the cells with a
      highly sensitive mechanism of regulation of the Ca(2+)-dependent proteolytic
      system.

PMID- 8147877
TI  - Characterisation of the nucleotide and DNA coeffector binding sites of the herpes
      simplex virus type 1 (HSV-1) encoded helicase-primase complex and UL9 origin
      binding protein.
AB  - Nucleotide and DNA coeffector substrate binding site characterizations were
      performed on two HSV-1 DNA helicases fulfilling different roles in DNA
      replication. Single ATP-binding sites were identified for helicase-primase and
      UL9 protein (Km(ATP) 0.62 mM and 0.54 mM, respectively). Analysis of structural
      requirements for DNA-dependent NTP hydrolysis revealed comparatively stringent
      requirements for helicase-primase in accommodating base-modified NTP analogs
      whereas the UL9 protein was much more permissive in this respect; neither enzyme
      was dependent on the ribose 2' or 3' hydroxyls for NTP hydrolysis. Both helicase
      primase and UL9 protein ATPase activities were inhibited by ADP or GDP; this
      effect was competitive rather than allosteric. The enhancement of ATPase activity
      on a single stranded (ss) DNA substrate as opposed to double stranded (ds) DNA
      was much more marked for helicase-primase than for the UL9 protein
      (Km(dsDNA)/Km(ssDNA) 60 and 9, respectively). The triphosphates of the antiviral
      agents acyclovir and penciclovir were not effective substrates for either
      helicase-primase or UL9 protein.

PMID- 8147878
TI  - Different expression of beta-N-acetylhexosaminidase in mouse tissues.
AB  - The expression of genes encoding for the alpha and beta-subunits of the lysosomal
      enzyme beta-N-acetylhexosaminidase was investigated in different mouse tissues.
      It was found, using fluorogenic substrates, that the amounts of alpha and beta
      subunits were not the same in different tissues: alpha-subunit was more abundant
      in the brain, beta-subunit in epididymis and brain. The different isoenzyme
      patterns and specific activities in mouse tissues are due to the differences in
      the amount of hexosaminidase subunits. The mRNA, evaluated by Northern blotting
      analyses, revealed a greater expression of alpha-subunit in the testis and of
      beta-subunit in the brain and epididymis. The results indicate, therefore, that
      gene expression and the amount of subunits are in good relationship for beta
      subunit, whereas there is no correlation for alpha-subunit.

PMID- 8147879
TI  - Synthetic cDNA encoding the rat AT1a receptor: a useful tool for structure
      function relationship analysis.
AB  - To carry out systematic structure-function studies of the rat angiotensin II
      receptors by site directed mutagenesis, or production of chimeric receptors, we
      have produced a synthetic cDNA coding for the AT1a receptor. The synthetic cDNA
      is 1101 base pairs long, and contains 49 unique restriction sites that are on the
      average 23 base pairs apart, allowing replacement of specific restriction
      fragments by synthetic counterparts containing the desired modified sequence. The
      total cDNA was assembled in the expression vector pECE. After stable expression
      in Chinese Hamster Ovary cells, the protein encoded by this synthetic cDNA
      presents a pharmacological profile and a signal transduction mechanism
      indistinguishable from the wild type rat AT1a receptor.

PMID- 8147880
TI  - Isolation of a yeast tropomyosin-related cDNA clone that encodes a novel
      transmembrane protein having a C-terminal highly basic region.
AB  - A novel cDNA clone was isolated from a yeast Saccharomyces cerevisiae lambda gt11
      cDNA library using rabbit anti-rat tropomyosin (TM30nm) polyclonal antibody (RTM8
      2). It consists of an open reading frame of 951 bp, encoding 317 amino acid
      residues. The putative sequence recognized by RTM8-2 was present in Asn-235 to
      Thr-250. The deduced amino acid sequence and hydropathy plot suggested that this
      protein has a tropomyosin-homologous sequence, a predicted transmembrane, and a C
      terminal basic region. A search of the data bases (EMBL and GenBank) revealed
      that the 128bp sequence in the 3' untranslated region (3'UTR) is almost identical
      (96.9%) to the human cDNA clone 54E05 sequence (EMBL accession number Z15978).

PMID- 8147881
TI  - Homologous dinucleotide (GT or TG) deletion in Japanese patients with chronic
      granulomatous disease with p47-phox deficiency.
AB  - The cytosolic 47-kDa protein designated as p47-phox (phagocyte oxidase) is one of
      the essential components of the superoxide-generating system in phagocytes, and
      its defect is known to cause chronic granulomatous disease (CGD). Five unrelated
      CGD patients with p47-phox deficiency were found among 82 CGD patients in Japan.
      We sequenced the cDNAs and the genomic DNAs corresponding to p47-phox derived
      from these patients. In all cases examined, the defect was identified to be a GT
      (or TG) dinucleotide deletion at bases 75/76 (or 74/75, respectively) in the
      coding sequence for the protein. The same mutation was reported previously for a
      total of 9 alleles from 5 CGD patients in England and in the United States. It
      seems, therefore, that the dinucleotide GT deletion is the common mutation in 47
      phox deficient CGD due to certain structural issues.

PMID- 8147882
TI  - A novel cytosolic component, p40phox, of respiratory burst oxidase associates
      with p67phox and is absent in patients with chronic granulomatous disease who
      lack p67phox.
AB  - Cytosolic components of human neutrophils, p47phox and p67phox, deficiencies of
      which lead to chronic granulomatous disease (CGD), potentiate respiratory burst
      oxidase translocating from cytosol to membrane upon cell stimulation. In this
      report we describe a novel cytosolic component, p40phox, which consistently
      behaves with p67phox through immunoprecipitation and column works, and is missing
      in patients with CGD who lack p67phox. Although actin has been reported to be
      involved in O2- generation, the p40phox profile did not correspond to that of
      actin. The tight association between p40phox and p67phox was not affected by
      treatment with a mixture of deoxycholate and Nonidet P-40, until subjected to SDS
      PAGE. Addition of recombinant p67phox to cytosol did not produce any additional
      p40phox in the immunoprecipitate, unlike the additive increment in the band of
      p67phox. These results suggest that p40phox forms a complex with p67phox in a
      molar ratio of 1:1, without any free p40phox in the cytosol.

PMID- 8147883
TI  - Calcium-binding activity of nucleobindin mediated by an EF hand moiety.
AB  - In a previous paper (Biochem. Biophys. Res. Commun. 187, 375-380, 1992), we
      reported cloning of a gene for nucleobindin (Nuc) from mouse and human. Nuc was
      identified as a secreted protein with DNA-binding properties. We noticed that Nuc
      includes two units of sequence similar to the EF hand motif, a calcium-binding
      motif, between a region rich in basic amino acids, which is presumably a DNA
      binding site, and a leucine zipper which is a dimerization motif. In the present
      study, we examined the calcium-binding activity of Nuc. Mouse and human
      recombinant Nuc (rNuc), as well as two mutant rNuc proteins, were synthesized in
      Escherichia coli. Mouse and human rNuc and one mutant rNuc, in which the region
      from the second EF hand motif to the C-terminus had been deleted, all had calcium
      binding activity. By contrast, another mutant rNuc in which both EF hand motifs
      had been deleted lacked this activity. Analysis by circular dichroism
      spectrometry indicated that addition of Ca2+ ions induces a structural change in
      Nuc, presumably an increase in the amount of alpha helix. However, addition of
      Ca2+ ions did not seem to cause any change in DNA-binding activity.

PMID- 8147884
TI  - Effects of estrogen and estrogen receptor in normal human melanocytes.
AB  - Normal human melanocytes were cultured selectively with F12 culture medium
      supplemented with growth hormones, phorbol ester and 1% of fetal calf serum. The
      estrogen receptors were analyzed using hydroxylapatite-column assay with
      tritiated 17-beta-estradiol as the binding ligand. Phenol red- free medium was
      used when the changes in cell numbers, melanin content and tyrosinase were
      assessed after incubating with physiological concentration of 17-beta estradiol
      (10(-12) and 10(-9) M). It was found that the melanocytes contained both cytosol
      (5.42 +/- 1.11 fmol/mg protein) and nuclear (59.13 +/- 17.12 fmol/mg protein)
      estrogen receptor. In response to estradiol, the cell number increased but both
      the melanin content and the tyrosinase activity decreased in a dose related
      pattern. These data suggested the presence of estrogen receptor with biological
      function in normal human melanocytes.

PMID- 8147885
TI  - Photophysical alterations of erythrocyte membrane by 4,5',8-trimethyl psoralen:
      membrane response towards psoralen phototherapy.
AB  - Despite the wide and versatile use of psoralen phototherapy in various dermal
      diseases including psoriasis and leukoderma, the proposed mechanism of action of
      psoralen is disputed. This study launches an original documentation of free
      radical resulting in erythrocyte membrane damage studied by spin-labeling using
      the probes malnet and 5 doxyl stearate as protein and lipid domains,
      respectively. Both Type I and Type II photodynamics appear plausible and the
      therapeutic aspects of this innovation are being verified.

PMID- 8147886
TI  - Nicotine downregulates alpha 2 isoform of Na,K-ATPase at the blood-brain barrier
      and brain in rats.
AB  - Effects of chronic nicotine treatment on the relative levels of expression of
      Na,K-ATPase alpha and beta subunit isoforms were determined in rat cerebral
      microvessels and capillary-depleted brain homogenates by Western blot analysis.
      Nicotine, 4.5 mg/kg/day, was administered s.c. by osmotic mini-pumps for 14 days.
      Expression of alpha 2 isoform in microvessels and brains of nicotine-treated rats
      was reduced to 0.26 and 0.58 of control levels, respectively. Expression of alpha
      1, alpha 3, beta 1 or beta 2 was unchanged. Nicotine decreased
      cerebromicrovascular and brain Na,ATPase enzymatic activities by 22% and 17%,
      respectively. It is suggested that chronic exposure to nicotine reduces
      expression of functional Na,K-ATPase at the blood-brain barrier and brain by
      downregulating the alpha 2 isoform.

PMID- 8147887
TI  - Characterization of rat pituitary cells by their responses to hypothalamic
      releasing hormones.
AB  - Rat pituitary cells in monolayer culture were characterized by their [Ca2+]i
      responses to hypothalamic releasing hormones, growth hormone (GHRH), thyrotropin
      releasing hormone (TRH), gonadotropin-releasing hormone (GnRH) and corticotropin
      releasing hormone (CRH). The percentages of the cell population responding to
      GHRH, TRH, GnRH, CRH and non-responding cells were 27.3%, 47.6%, 13.8%, 6.2% and
      35.3%, respectively. Some of the cells responded to two or more of those
      hormones. In the GHRH-responding cells, the population of TRH-responding cells
      was 51.4%, In the TRH-responding cells, the population of GHRH-responding cells
      was 30.8%. Some of the GHRH-responding cells also responded to CRH and GnRH. In
      the GnRH-responding cells, the population of TRH-responding cells was 61.8%. In
      summary, GHRH-responding cells have an especially close relationship with TRH
      responding cells, and GnRH-responding cells also have close relationship with TRH
      responding cells. There is also some relationship between the populations
      responding to other pairs of releasing hormones. These findings suggest
      functional overlapping among each population of pituitary cells.

PMID- 8147888
TI  - Inhibition of matrix metalloproteinases by peptidyl hydroxamic acids.
AB  - Synthetic inhibitors of interstitial collagenase, tri- and tetrapeptidyl
      hydroxamic acids, have been developed and tested for their inhibitory activities
      against human matrix metalloproteinases. A water soluble inhibitor, p-NH2-Bz-Gly
      Pro-D-Leu-D-Ala-NHOH (FN-439) inhibited interstitial and granulocyte
      collagenases, granulocyte gelatinase and skin fibroblast stromelysin with IC50 of
      1 x 10(-6) M, 3.0 x 10(-5) M and 1.5 x 10(-4), respectively, but not thermolysin
      and serine proteinases. FN-439 was found to retain its inhibitory activity
      against matrix metalloproteinases even after prolonged incubation with pronase or
      human granulocyte elastase, indicating a favorite candidate of the inhibitor to
      modulate metalloproteinase activities in vivo.

PMID- 8147889
TI  - A possible involvement of tyrosine kinase in TRH-induced prolactin secretion in
      GH3 cells.
AB  - Thyrotropin-releasing hormone (TRH) is a well-known regulatory factor of
      prolactin (PRL) secretion and synthesis in lactotrophs. Recently we have found
      that TRH stimulates early tyrosine phosphorylation of MAP kinase in GH3 cells.
      Then we investigated whether tyrosine phosphorylation in TRH action is involved
      in TRH-stimulated PRL secretion by GH3 cells, using a 4-hydroxycinnamamide
      derivative (ST638), a tyrosine kinase inhibitor. TRH-stimulated tyrosine
      phosphorylation of MAP kinase and PRL secretion were remarkably inhibited by
      ST638 treatment. These results suggest that tyrosine phosphorylation of MAP
      kinase is strongly associated with TRH-stimulated PRL secretion.

PMID- 8147890
TI  - Hepatocyte growth factor accelerates the wound repair of cultured gastric mucosal
      cells.
AB  - Effects of hepatocyte growth factor (HGF) on gastric wound repair were assessed.
      Artificial wounds of uniform size were made by mechanical cell denudation in
      confluent rabbit gastric mucosal cell sheets. The changes in wound size were
      analyzed quantitatively. The wound repair process contained an initial migration
      stage and a later proliferation stage. The wound was completely repaired in 36 h
      in controls; this repair was accelerated by HGF with the induction of cell
      migration followed by proliferation and was retarded by tyrosine protein kinase
      inhibitor genistein. HGF might play some roles in gastric ulcer healing.

PMID- 8147891
TI  - Clearance of circulating endothelin-1 by ETB receptors in rats.
AB  - Exogenous endothelin (ET) is rapidly cleared from the circulation. We
      investigated which ET receptor subtypes (ETA and ETB) participate in ET-1
      clearance. Following an intravenous (i.v.) bolus dose of [125I]ET-1 in
      anesthetized rats, radioactivity was rapidly cleared from the circulation and
      trapped by the lungs, kidneys and liver. Tissue distribution of the radioactivity
      was significantly inhibited in the lungs and kidneys, but not in the liver by
      infusion of the ETB antagonist BQ-788 (0.1 mg/kg/min i.v.), and the ET-1
      clearance rate was reduced, while the ETA antagonist BQ-123 had no such effect.
      Furthermore, in isolated perfused rat lungs, about 80% of bolus-injected [125I]ET
      1 was retained by the lungs after one passage. The retention of ET-1 was
      significantly inhibited by infusion of 1 microM BQ-788, but not BQ-123. These
      results suggest that ETB receptors play an important role in the clearance of ET
      1.

PMID- 8147892
TI  - Activation of src family kinase lck following CD28 crosslinking in the Jurkat
      leukemic cell line.
AB  - T lymphocytes require a signal via their antigen specific receptors (the T cell
      receptors) and an antigen independent costimulatory signal. Signals through CD28
      can costimulate T cells in the presence of limiting amounts of T cell receptor
      signal, or in the presence of PMA, providing this second signal. CD28 signaling
      is known to involve the activation of protein tyrosine kinases. Using the Jurkat
      leukemic cell line as a model, we have tested CD28 crosslinking for its effects
      on the protein tyrosine kinases p56lck. We report that following crosslinking of
      CD28, p56lck kinase activity is increased. Crosslinking CD28 causes a shift in
      the relative mobility of p56lck from 56 to 60 kD similar to that seen after
      crosslinking of CD2 and CD4, cell surface receptors known to be associate with
      and activate p56lck. Finally, lck could be found in anti-CD28 immunoprecipitates
      in exponentially growing Jurkat and in "activated" CD28 (i.e., cross linked), but
      not in CD28 in resting Jurkat cells. These findings suggest an important role for
      p56lck in CD28 signal transduction.

PMID- 8147893
TI  - Identification of the third major genotype of hepatitis C virus in France.
AB  - We have previously found type I and type II hepatitis C virus (HCV) as the
      predominant HCV genotypes in France. Here we report on the identification and
      partial characterization of a third major genotype there. This genotype showed
      only 93-94% sequence conservation to either type I or type II HCV in the 5'
      noncoding region. The point mutations changed the small open reading frames but
      not the proposed secondary structure of this region. Sequence of the structural
      protein region also differed significantly from other genotypes. The new genotype
      was found in 12% of HCV infections in France. Rapid method for the identification
      of this genotype was developed.

PMID- 8147894
TI  - Thyroid hormone influences beta myosin heavy chain (beta MHC) expression.
AB  - 3,5,3'-Triiodo-L-thyronine (T3) regulation of beta-MHC expression was studied in
      rat fetal heart cells using deletion mutants of both the rat and human promoter
      regions fused to a CAT expression vector. T3 inhibited the expression of human
      and rat beta-MHC constructs with an IC50 of about 1nM, which was similar to the
      EC50 for beta MHC-mRNA observed in cardiomyocytes. Deletion analysis of beta MHC
      promoter constructs suggested that a T3 response element (TRE) is located near
      the start of transcription. Possibly, T3-receptor binding at this site interferes
      with formation of the transcriptional initiation complex.

PMID- 8147895
TI  - Porphyromonas gingivalis trypsin-like protease: a possible natural ligand for the
      neutrophil formyl peptide receptor.
AB  - Porphyromonous gingivalis is a periodontopathic Gram-negative anaerobe associated
      with chronic adult periodontitis. P. gingivalis proteases are considered
      important virulence factors in the pathogenesis of periodontal diseases. In
      addition, defective bactericidal activity of neutrophils has also been observed
      in periodontitis. In this report we describe the effects of trypsin-like
      protease(s) secreted from P. gingivalis cells on the ligand binding of FMLP
      receptor on neutrophils. It was observed that trypsin-like protease(s) from P.
      gingivalis stimulate neutrophils by means of superoxide anion production.
      Subsequently, the proteases were found to cleave the FMLP receptor protein as
      evident by direct labeling of the FMLP receptor molecule. These results suggest
      that trypsin-like protease(s) secreted from P. gingivalis cells contribute to
      attenuate the bactericidal activity of neutrophils by cleaving the polypeptide
      chain of the FMLP receptor molecule. The finding that neutrophils after the
      incubation with P. gingivalis released protease preparation fail to respond to
      further stimulation by FMLP suggests that P. gingivalis trypsin-like protease(s)
      may be a possible ligand for the FMLP receptor.

PMID- 8147896
TI  - The intracellular region adjacent to plasma membrane (residues 684-692) of the
      thyrotropin receptor is important for phosphoinositide signaling but not for
      agonist-induced adenylate cyclase activation.
AB  - We investigated the role of the intracellular region adjacent to transmembrane
      helix VII of the thyrotropin receptor (TSHR) in signal transduction using mutants
      as we did on the cytoplasmic loops. Two mutants with a substitution of the alpha
      1- or beta 2-adrenergic receptor sequence showed a TSH- or Graves' IgG-stimulated
      cAMP response despite a low TSH binding Bmax. Both the mutants completely lost or
      markedly decreased the TSH- or Graves' IgG-stimulated inositol phosphate
      increase. These findings suggest that the intracellular region adjacent to the
      transmembrane region (residues 684-692) of the TSHR does not play a crucial role
      in agonist-induced adenylate cyclase activation but that it is important for
      phosphoinositide signaling.

PMID- 8147897
TI  - The binding of fibronectin to entactin is mediated through the 29 kDa amino
      terminal fragment of fibronectin and the G2 domain of entactin.
AB  - Previous work has shown that fibronectin and entactin, an ubiquitous basement
      membrane glycoprotein, co-localize in the extracellular matrix of the embryonal
      carcinoma-derived 4CQ cell. Glutathione-S-transferase (GST) fusion proteins
      containing different domains of entactin have been obtained in the pGEX3X
      expression vector. These fusion proteins, GST-G1, GST-G2, GST-E and GST-G3, were
      purified with a glutathione affinity column. By using a solid phase binding
      assay, it was shown that the 125I-labeled 29 kDa amino terminal fragment of
      bovine fibronectin bound specifically to the immobilized GST-G2 fusion protein
      but not to GST-G1, GST-E, and GST-G3. Half saturation for binding of the 29 kDa
      fibronectin fragment to the immobilized GST-G2 fusion protein was obtained at a
      concentration of approximately 5 nM. It is suggested that the strong association
      between GST-G2, which contains the second globular domain of entactin, and the 29
      kDa amino terminal fragment of fibronectin may be involved in the assembly of
      certain types of extracellular matrices.

PMID- 8147898
TI  - Glucose transporter GLUT1 mRNA expression in the ontogeny of glucose
      incorporation in mouse preimplantation embryos.
AB  - Glucose incorporation and utilization in mouse embryos increases during
      preimplantation development. A reverse transcription-polymerase chain reaction
      (RT-PCR) was applied to quantitatively determine the levels of glucose
      transporter GLUT1 mRNA in preimplantation mouse embryos. The levels of GLUT1 mRNA
      increased during embryonic development, and it was 11-fold greater in blastocysts
      than in 2-cell embryos. Similar increases were observed in glucose incorporation
      as measured by 2-deoxyglucose uptake in the embryos. Increases in GLUT1 mRNA and
      glucose uptake are also observed when 2-cell embryos are developed to blastocysts
      in vitro, although the levels are one-third to half of those of the in vivo
      blastocysts. These results suggest that glucose incorporation during
      preimplantation development depends at least in part on the expression of GLUT1
      mRNA transcription, which results in increased amounts of GLUT1 protein and that
      the difference in its expression in vivo and in vitro may serve as a clue for
      studying the preimplantation development of embryos.

PMID- 8147899
TI  - Interaction of ebselen with glutathione S-transferase and papain in vitro.
AB  - The interaction of ebselen(2-phenyl-1,2-benzisoselenazol-3(2H)-one) with rat
      liver cytosolic glutathione S-transferases (GSTs) and the plant cysteine
      protease, papain, was studied as cysteine residues are important for the activity
      of these enzymes. The capacity of GST 1-2 and 3-4 for ebselen binding is similar
      (1.5 mol ebselen/mol GST isozyme), while GST 2-2 and GST 7-7 bind 0.3 and more
      than 2.0 mol ebselen/mol GST isozyme, respectively. Ebselen does not bind to N
      ethylmaleimide-treated GST, and its binding to GST is prevented by 5 mM thiols.
      Ebselen irreversibly inactivates the different GST isozymes with a second order
      rate constant ranging from 20 to 2250 M-1 sec-1 for the different subunits. GST
      inhibition by ebselen is partially restored by 5 mM thiols. Ebselen binds to
      untreated papain and to cysteine-treated papain at a ratio of about 0.1 and 0.75
      mol ebselen/mol papain, respectively. Ebselen does not bind to N-ethylmaleimide
      treated papain, and its binding to papain is interfered with by added thiols.
      Papain is inactivated by ebselen with a second order rate constant of 1800 M-1
      sec-1 in the absence of thiols. However, in the presence of GSH, 2
      mercaptoethanol or sodium borohydride, ebselen exerts an activating effect on
      papain. The binding of ebselen by a seleno-sulfide bond to cysteine residues of
      GSTs and papain leads to their inactivation.

PMID- 8147900
TI  - Effects of suramin on increases in cytosolic calcium and on inhibition of
      adenylate cyclase induced by adenosine 5'-diphosphate in human platelets.
AB  - The effects of the P2-purinoceptor antagonist, suramin, on ADP-induced increases
      in human platelet cytosolic calcium concentration ([Ca2+]i) and inhibition of
      prostaglandin E1 (PGE1)-stimulated adenylate cyclase activity were investigated.
      Suramin (50-200 microM) acted as an antagonist of ADP-induced increases in
      [Ca2+]i, causing parallel, rightward shifts of the log concentration-response
      curve to ADP with no apparent depression of the maximal response. However, the
      slope of the Schild plot was 2.3 +/- 0.3, similar to that obtained in previous
      studies on aggregation, indicating that the antagonism was not simply
      competitive. The apparent pA2 for suramin, taken from the Schild plot, was 4.63,
      similar to that for suramin's inhibition of aggregation, which suggests that
      these two effects are closely related. Suramin was not specific for the ADP
      receptor, however, as it was also able to inhibit, non-competitively, increases
      in [Ca2+]i induced by 5-hydroxytryptamine. Suramin (50-400 microM) also inhibited
      the effect of ADP on PGE1-stimulated accumulation of cyclic AMP, causing parallel
      shifts of the log concentration-response curve to ADP, with a Schild plot slope
      of 1.00 +/- 0.10, suggesting competitive antagonism, and a pA2 value of 5.09.
      Suramin (400 microM) did not reduce the inhibition of cyclic AMP accumulation by
      adrenaline, although it was able to inhibit the accumulation of cyclic AMP caused
      by PGE1, again showing that suramin has some non-specific effects. These data
      suggest that suramin is an antagonist at the platelet ADP receptor mediating
      increases in [Ca2+]i and inhibition of adenylate cyclase, but that it also shows
      non-specific effects and can depress platelet responses to other agonists. In
      addition, the similar pA2 value of suramin for the two effects of ADP does not
      support suggestion that they are mediated by two different receptors on human
      platelets.

PMID- 8147901
TI  - Contrasting effects of two arachidonate 5-lipoxygenase inhibitors on formyl
      methionyl-leucyl-phenylalanine (fMLP) and complement fragment 5a induced human
      neutrophil superoxide generation.
AB  - SC-45662 and SC-41661A, selective arachidonate 5-lipoxygenase (5-LO) inhibitors,
      had markedly different effects on formyl-methionyl-leucyl-phenylalanine (fMLP)
      and complement fragment 5a (C5a) induced superoxide release from human
      neutrophils (PMNs). SC-45662 inhibited superoxide generation induced by fMLP and
      C5a with IC50 values of 12 and 5 microM, respectively. Furthermore, SC-45662 was
      capable of inhibiting fMLP and C5a induced superoxide release in PMNs primed with
      bacterial lipopolysaccharide, tumor necrosis factor-alpha and other priming
      agents. SC-41661A, a compound from the same chemical series as SC-45662, did not
      inhibit or induce superoxide generation, but instead primed PMNs for fMLP and C5a
      induced superoxide generation. The induced superoxide release was concentration
      dependently enhanced 2 to 4-fold at 5-50 microM. Superoxide release induced by
      phorbol myristate acetate or serum-activated zymosan was unaffected by either SC
      45662 or SC-41661A. The regulation of superoxide generation by these compounds,
      both of which have the identical oxidation-reduction pharmacophore, was clearly
      independent of their effects on 5-LO activity. Furthermore, the mechanism by
      which SC-45662 and SC-41661A alter superoxide generation did not appear to depend
      on inhibition of xanthine oxidase, catalase or superoxide dismutase. These new
      compounds provide effective tools for further investigation of the relationship
      of these two biochemical oxidative systems.

PMID- 8147902
TI  - Aromatic hydroxylation during the myeloperoxidase-oxidase oxidation of
      hydrazines.
AB  - Benzoic acid was found to be hydroxylated by a mixture of myeloperoxidase (MPO)
      and the mycobactericidal drug, isoniazid. Aromatic hydroxylation and formation of
      compound III (oxyperoxidase) were coincident during the MPO-oxidase oxidation of
      isoniazid which proceeded without augmentation from the reagent hydrogen
      peroxide. An intermediate of isoniazid reduced ferric MPO to ferrous MPO which
      associated with dioxygen to form compound III. Aromatic hydroxylation also
      occurred in a mixture of isoniazid (or phenylhydrazine) and a ferric salt.
      Hydroxylations in both the enzymatic and nonenzymatic reaction systems were
      inhibited by the iron chelator, desferal, as well as by the specific hydroxyl
      radical scavenger, mannitol. To distinguish between the hydroxylating
      intermediates in the different reaction systems, the unique properties of the
      natural antioxidant, phytic acid, were exploited. Phytic acid inhibited aromatic
      hydroxylation in the Fe(3+)-INH system, which is in accordance with its known
      properties as a powerful inhibitor of iron-driven reactions (.OH formation). By
      contrast, phytic acid stimulated hydroxylation in the enzymatic system which was
      accompanied by a concomitant stimulation in the rate of compound III formation.
      These events were, however, not directly related to each other. Phytic acid had a
      direct effect on the redox transformation of isoniazid by stimulating superoxide
      generation during auto-oxidation of the drug. In addition, phytic acid also
      facilitated compound III decay in the absence of isoniazid, suggesting that it
      may also regulate the oxygen affinity of MPO, similar to its effect on the
      oxygenation of haemoglobin. The data on aromatic hydroxylation in the MPO
      isoniazid system do not support a role for .OH in the reaction and may fit the
      model for the P450 mixed oxidase system.

PMID- 8147903
TI  - Direct demonstration of NO formation in vivo from organic nitrites and nitrates,
      and correlation to effects on blood pressure and to in vitro effects.
AB  - Previous studies, utilizing nitric oxide synthase inhibitors and nitric oxide
      application, indicate that nitric oxide has the capacity to modulate contractile
      responses in pulmonary vessels. In the present study, in vitro effects of organic
      nitrates/nitrites were compared with their in vivo ability to generate nitric
      oxide and their effects on blood pressure. Glyceryl trinitrate, ethyl nitrite,
      isobutyl nitrate, isobutyl nitrite, isoamyl nitrite and butyl nitrite inhibited
      contractions in response to nerve stimulation in guinea pig pulmonary artery and
      vas deferens. Glyceryl trinitrate (also known as nitroglycerin) was the most
      potent and isobutyl nitrate the least potent substance with this action (IC50 4.5
      +/- 0.2 x 10(-10) and 1.1 +/- 0.1 x 10(-5) M, respectively). Contractile
      responses to noradrenaline were inhibited, whereas noradrenaline release was
      unaffected by organonitrates/nitrites, indicating a post-junctional inhibitory
      effect. When infused intravenously to anaesthetized rabbits glyceryl trinitrate,
      ethyl nitrite and isobutyl nitrate generated dose-dependent increments of nitric
      oxide in exhaled air and dose-dependent decrements in systemic blood pressure.
      Significant correlations were obtained between in vivo NO generation and effects
      on blood pressure, as well as between NO generation in vivo and the in vitro
      activity of the organic nitrites and organic nitrates. In conclusion, organic
      nitrites and organic nitrates can modulate adrenergic neuroeffector transmission
      in guinea pig pulmonary artery and vas deferens, and produce detectable
      concentrations of nitric oxide in exhaled air in vivo, in the rabbit. The
      observations give direct in vivo evidence that organic nitrites and nitrates
      generate NO, and strongly support them exerting their action via NO formation.

PMID- 8147904
TI  - Characterization of human serum and umbilical artery semicarbazide-sensitive
      amine oxidase (SSAO). Species heterogeneity and stereoisomeric specificity.
AB  - Semicarbazide-sensitive amine oxidases (SSAOs) are located in cardiovascular
      smooth muscle, cartilage and brown adipose tissues of different species,
      including human. The enzyme is also present in blood, and its activity appears to
      be altered under certain pathological conditions. SSAOs from both human umbilical
      arteries and serum were partially purified, and some of their biochemical
      properties were investigated. Both human artery and blood SSAO exhibited very
      similar substrate preference, lack of stereospecificity catalyzing the
      deamination of pro-R and pro-S benzylamine-deuterated enantiomers, and were very
      sensitive towards (E)-2-(4-fluorophenethyl)-3-fluoroallylamine (MDL-72974A). It
      was concluded that circulating serum SSAO is identical to the SSAO from vascular
      tissues. Human SSAO exhibited distinctly different properties in comparison to
      bovine and rat SSAOs.

PMID- 8147905
TI  - Metabolism of lidocaine by rat pulmonary cytochrome P450.
AB  - The metabolism of lidocaine was studied using microsomes from extrahepatic
      tissues of rats, including lung, kidney and brain, or using a reconstituted
      system with purified CYP2B1 and CYP4B. Rat pulmonary microsomes metabolized
      lidocaine to an N-deethylated metabolite, monoethylglycinexylidide (MEGX). Renal
      microsomes produced MEGX and 3-hydroxylidocaine (3-OH LID), although the rate of
      MEGX formation was much lower in renal than in pulmonary microsomes. Other
      metabolites were not detected. Lidocaine was not metabolized by brain microsomes.
      In extrahepatic tissues, pulmonary microsomes had the highest activity. Hence,
      two major forms of cytochrome P450 isozymes, CYP2B1 and CYP4B1, in rat pulmonary
      microsomes were used for further study. The study with a reconstituted system
      using purified cytochrome P450 isozymes revealed that only CYP2B1 showed
      lidocaine deethylation activity; the other form of cytochrome P450 in the lung,
      CYP4B1, did not. The Michaelis-Menten constant for lidocaine N-deethylation by
      rat pulmonary microsomes was 0.27 mM. Antibody against CYP2B1 completely
      inhibited the formation of MEGX by pulmonary microsomes. These results suggest
      that lidocaine is metabolized by rat lung, including CYP2B1.

PMID- 8147906
TI  - Effect of purine synthesis inhibition on WiDr spheroids in vitro or on WiDr or
      colon 38 tumors in vivo. Complete growth inhibition but not regression.
AB  - Clinical responses for anticancer agents are based upon tumor regression. We have
      investigated the potential of glycineamide ribonucleotide transformylase (GAR
      TFase) inhibitors to produce regressions in multiple preclinical models of colon
      carcinoma. The growth of multicellular tumor spheroids of WiDr human colon
      carcinoma was inhibited by the GAR TFase inhibitors 5-deazaacyclotetrahydrofolate
      (5-DACTHF), its 2'-fluoro, 3'-fluoro, 10-deaza, and 10-thia analogs as well as
      5,10-dideazatetrahydrofolate, but none of the compounds caused spheroid
      regressions. By contrast, complete spheroid disruption was observed with exposure
      to etoposide, m-AMSA (amsacrine), piritrexim, or 2-desamino-2-methyl-10-propargyl
      5,8-dideazafolate (DMPDDF). Light microscopy of the spheroids treated with either
      5-DACTHF or DMPDDF suggested that the reason for the difference is extensive cell
      kill throughout the spheroid in the presence of DMPDDF compared with little or no
      kill, over that found in controls, with 5-DACTHF. Treatment of spheroids with 5
      DACTHF in the presence of 1 microM hypoxanthine resulted in no significant
      reversal of growth inhibition; 50% reversal required 10 microM hypoxanthine. The
      spheroid studies were extended to in vivo studies examining the effects of 5
      DACTHF on established WiDr and colon 38 tumors. The results showed that, in
      contrast to melphalan, which produced cures and tumor regressions, 5-DACTHF
      produced reversible growth inhibition with no significant regression of tumors.
      The results predict that clinical response, typically measured by tumor
      regression, may be rare following single agent therapy with inhibitors of de novo
      purine biosynthesis.

PMID- 8147907
TI  - Role of cellular glutathione and glutathione S-transferase in the expression of
      alkylating agent cytotoxicity in human breast cancer cells.
AB  - Glutathione (GSH) and glutathione S-transferases (GSTs) play an important role in
      the protection of cells against toxic effects of many electrophilic drugs and
      chemicals. Modulation of cellular GSH and/or GST activity levels provides a
      potentially useful approach to sensitizing tumor cells to electrophilic anti
      cancer drugs. In this study, we describe the interactions of four representative
      alkylating agents (AAs), melphalan, 4-hydroperoxy-cyclophosphamide (4HC), an an
      activated form of cyclophosphamide, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU),
      and cisplatin, with GSH and GST in the human breast cancer cell line MCF-7.
      Depletion of cellular GSH pools by approximately 80% by treatment of the cells
      with the GSH synthesis inhibitor buthionine sulfoximine (BSO) sensitized the
      tumor cells to each AA to a different extent, with dose-modifying factors of
      2.39, 2.21, 1.64, and 1.27 observed for melphalan, 4HC, cisplatin, and BCNU,
      respectively. Treatment of the cells with the GST inhibitor ethacrynic acid (EA)
      failed to show any significant effects on the cytotoxicity of these AAs. However,
      EA did potentiate the cytotoxicity of melphalan when given in combination with
      BSO, an effect that may be due to a more complete depletion of cellular GSH
      levels by the combined modulator treatment. Following a 1-hr exposure to
      cytotoxic-equivalent concentrations of these AAs, GSH levels decreased
      substantially in the case of 4HC and BCNU, but increased by 30-50% in the case of
      cisplatin and melphalan. BSO pretreatment largely blocked this effect of
      cisplatin and melphalan on cellular GSH, while it further enhanced the GSH
      depleting activity of both 4HC and BCNU. On the basis of these results, it is
      concluded that (a) GSH affects the cytotoxicity of different AAs to different
      extents, (b) basal GST expression in MCF-7 cells does not play a major role in AA
      metabolism, (c) EA can potentiate the enhancing effect of BSO on melphalan
      cytotoxicity in MCF-7 cells, and (d) depletion of cellular GSH by pretreatment
      with BCNU or cyclophosphamide may correspond to a useful strategy for enhancing
      the anti-tumor activity of other AAs given in a sequential combination.

PMID- 8147908
TI  - Bestatin transport in rabbit intestinal brush-border membrane vesicles.
AB  - The effect of papain treatment on bestatin uptake by rabbit intestinal brush
      border membrane vesicles (BBMVs) was studied. Papain treatment of BBMVs
      effectively diminished aminopeptidase activity but not bestatin uptake by a
      H+/dipeptide cotransporter. Bestatin uptake by BBMVs was composed of two
      saturable components, and after papain treatment the high-affinity component
      disappeared while the low-affinity component was retained. These findings suggest
      that high- and low-affinity components represent bestatin binding to
      aminopeptidase and the true uptake by the H+/dipeptide cotransporter,
      respectively.

PMID- 8147909
TI  - Increase of UDP-glucuronosyltransferase activities toward xenobiotics during the
      development of hereditary hepatitis in LEC rats.
AB  - UDP-glucuronosyltransferase activities were induced spontaneously during the
      development of hepatitis in LEC (Long Evans Cinnamon-like coat color) rats.
      Transition of hepatic microsomal UDP-glucuronosyltransferase activities was
      observed during the development of the LEC rat, which displayed spontaneous
      fulminant hepatitis with severe jaundice at about 12-16 weeks after birth. UDP
      glucuronosyltransferase activities toward various substrates in 8-week-old LEC
      and LEA (Long Evans Agouti coat color; control) rats were similar. After 8 weeks
      of age, the transferase activities of LEA rats towards all substrates tested,
      except for bilirubin, decreased slightly during the next 24 weeks. In LEC rats,
      the transferase activities towards serotonin and several phenolic xenobiotics,
      such as 4-nitrophenol, 1-naphthol and 4-methylumbelliferone, but not 4
      hydroxybiphenyl, increased about 2-fold at 16 weeks of age. During the 24 weeks
      following the first 8 weeks of age, the high level activities towards the
      xenobiotics continued, with the exception of bilirubin transferase activity which
      decreased gradually. These results suggest that a form of UDP
      glucuronosyltransferase, which catalyzes the glucuronidations of serotonin and
      these xenobiotics except for 4-hydroxybiphenyl, is induced during the development
      of hepatitis in the LEC rat.

PMID- 8147910
TI  - Role of N-glycosylation in the structure and function of the methotrexate
      membrane transporter from CCRF-CEM human lymphoblastic leukemia cells.
AB  - The carrier protein for methotrexate and tetrahydrofolate cofactors (GP-MTX) in
      CCRF-CEM human lymphoblastic leukemia cells in a 117 kDa glycoprotein containing
      both N- and O-linked oligosaccharides (Matherly et al., J Biol Chem 267: 23253
      23260, 1992). Tunicamycin, an inhibitor of N-glycosylation, was used to
      investigate the roles of asparagine-linked oligosaccharides in the structure,
      intracellular routing, and transport function of GP-MTX. Tunicamycin was growth
      inhibitory toward CCRF-CEM cells (IC50-0.80 micrograms/mL) and caused a potent
      suppression of [3H]mannose incorporation into nascent glycoproteins. From 1-3
      micrograms/mL, inhibition of [3H]mannose incorporation was 66-87%, exceeding that
      for [35S]methionine incorporation by 2 to 4-fold. Tunicamycin (1 and 2
      micrograms/mL) exposures decreased the median molecular masses of GP-MTX on
      immunoblots (to 82 and 67 kDa, respectively) and were accompanied by reduced
      maximal rates of methotrexate uptake (31 and 37%, respectively, of control
      levels). Conversely, the Ki values for methotrexate binding to the transporter
      were unaffected by tunicamycin treatments. The effects of tunicamycin on
      methotrexate influx closely correlated with lower levels of immunoreactive GP-MTX
      in plasma membranes and specific [3H]methotrexate binding to intact cells,
      suggesting that the transport effect was due to decreased numbers of carrier
      proteins at the membrane surface. The reduced molecular mass values for GP-MTX,
      which accompanied tunicamycin exposures, were further decreased (to 55 and 50 kDa
      at 1 and 2 micrograms/mL, respectively) by digestions with N-glycanase. Hence,
      despite the large loss of N-glycan from GP-MTX in tunicamycin-treated cells,
      residual core oligosaccharides remained. The sizes of hypoglycosylated GP-MTX
      following both treatments were similar to that of the functionally homologous
      methotrexate membrane carrier previously identified in L1210 murine leukemia
      cells.

PMID- 8147911
TI  - Morin: a wood pigment that protects three types of human cells in the
      cardiovascular system against oxyradical damage.
AB  - Morin is a yellowish pigment extractable from the wood of Chlorophora tinctoria.
      In the present study, we have determined that morin protects three types of human
      cells--ventricular myocytes, saphenous vein endothelial cells, and erythrocytes-
      against damage by oxyradicals generated in situ. In myocytes and endothelial
      cells, morin prolonged substantially and in a concentration-dependent manner the
      survival of cells exposed to either xanthine oxidase-generated oxyradicals or
      superoxide radicals produced with menadione. Morin protected erythrocytes from
      lytic attack by peroxyl radicals generated with 2,2'-azo-bis (2-amidinopropane)
      dihydrochloride. In all three types of human cells, the protective effect of
      morin clearly excelled that displayed by Trolox (a vitamin E analog), ascorbate,
      or mannitol, which are water-soluble antioxidants of similar molecular size.
      Chemically, we verified that morin behaves as an antioxidant by diminishing
      markedly the amount of malondialdehyde (lipid peroxidation product) found in
      human cardiocytes despite their exposure to oxyradicals. In agreement with
      related reports, we also observed that morin is non-toxic in rats even when used
      at concentrations 2-3 orders of magnitude higher than those in our in vitro
      studies. Thus, morin acts as a broad-spectrum and non-toxic antioxidant.

PMID- 8147912
TI  - Lipocortin-derived peptides.

PMID- 8147913
TI  - Halothane and isoflurane enhance basal and carbachol-stimulated
      inositol(1,4,5)triphosphate formation in SH-SY5Y human neuroblastoma cells.
AB  - The cellular mechanisms underlying the clinical effects of volatile anaesthetics
      remain unknown, although the plasma membrane and its associated proteins are
      likely targets. One such protein is the enzyme phospholipase C (PLC), which
      catalyses the formation of the second messenger inositol(1,4,5)triphosphate
      [Ins(1,4,5)P3]. Using SH-SY5Y human neuroblastoma cells we have demonstrated that
      halothane (0.50, 0.75 and 1.00%) enhances basal Ins(1,4,5)P3 mass formation
      approximately 1.8-fold. Halothane also caused a dose-dependent enhancement of
      carbachol-stimulated biphasic Ins(1,4,5)P3 formation at both the peak (half
      maximal stimulation, EC50 = 0.76%) and plateau (EC50 = 0.74%) phases. At 1%,
      halothane did not alter the affinity for carbachol at either the peak (IC50: air
      = 9.4 +/- 1.5, halothane = 12.7 +/- 1.0 microM) or plateau (EC50: air = 11.7 +/-
      1.2, halothane = 11.6 +/- 1.0 microM) phase, but did increase the maximum
      Ins(1,4,5)P3 response at both phases (air vs halothane: peak, 79.9 +/- 0.5 vs
      124.8 +/- 2.5; plateau, 33.2 +/- 0.5 vs 47.9 +/- 0.6 pmol/mg protein). Isoflurane
      (2%) also enhanced basal and carbachol-stimulated Ins(1,4,5)P3 formation 2-fold
      and 1.5-fold, respectively. In summary, clinically relevant doses of the volatile
      anaesthetics halothane and isoflurane enhance basal and carbachol-stimulated
      Ins(1,4,5)P3 formation. Thus, activation of PLC, and subsequent potential
      Ins(1,4,5)P3-mediated rises in intracellular calcium, could play a part in the
      cellular mechanisms of volatile agent-induced anaesthesia.

PMID- 8147914
TI  - Bradykinin B2- and 5-hydroxytryptamine (5-HT2)-receptor stimulated increases in
      intracellular calcium in cultured guinea-pig aortic smooth muscle cells.
AB  - The effect of 5-hydroxytryptamine (5-HT) and bradykinin on intracellular free
      calcium concentration ([Ca2+]i) has been studied in cultured guinea-pig aortic
      smooth muscle cells loaded with the Ca(2+)-sensitive fluorescent dye fura-2.
      Bradykinin and 5-HT elicited rapid increases in [Ca2+]i with log EC50 values of 
      7.9 +/- 0.05 M (N = 3) and -6.1 +/- 0.1 M (N = 4), respectively. Both agonists
      stimulated the release of intracellular calcium (Ca2+ responses still present in
      the absence of extracellular calcium) and to a lesser extent Ca2+ influx
      (observed when extracellular calcium was re-applied to cells initially stimulated
      in nominally Ca(2+)-free buffer containing 0.1 mM EGTA). The B1-receptor
      antagonist des-Arg9,[Leu8]-bradykinin had no effect on calcium responses elicited
      100 nM bradykinin, whereas the B2-receptor antagonist D-Arg[Hyp3,Thi5.8,D-Phe7]
      bradykinin (10 microM) inhibited the response to 100 nM bradykinin by 43%. The
      bradykinin B2-receptor antagonist D-Arg[Hyp3,Thi5.8,D-Phe7]-bradykinin virtually
      abolished the response to 10 nM bradykinin (IC50 4 microM). No increase in
      [Ca2+]i was observed with the B1-receptor agonist des-Arg9-bradykinin (300 nM).
      The response to 5-HT (100 microM) was abolished by the 5-HT2 receptor antagonist
      ketanserin (IC50 = 2 +/- 0.4 nM; N = 3). These data suggest that in cultured
      guinea-pig aortic smooth muscle cells bradykinin B2- and 5-HT2-receptor
      activation stimulates the release of Ca2+ from intracellular stores and Ca2+
      influx through Ca2+ entry pathways in the plasma membrane.

PMID- 8147915
TI  - Effect of chemical modification of arginyl and histidyl residues on [3H]MK-801
      binding to brain synaptic membranes.
AB  - Chemical modification of the N-methyl-D-aspartate (NMDA) receptor was
      investigated in a thoroughly washed Triton-treated pig forebrain membrane
      preparation. Modification of arginyl residues using phenylglyoxal significantly
      reduced activation of the NMDA receptor as measured by specific binding of [3H]MK
      801 [(+)-5-methyl-10,11-dihydro-dibenzo[a,d]cyclohepten-5,10-imine]. The
      reduction was due to a decrease in the affinity of MK-801 for its binding site
      from 3.2 +/- 0.5 nM to 22 +/- 8 nM. Protection studies indicated that alteration
      of the glutamate or glycine binding sites is not directly responsible for the
      effect. Diethyl pyrocarbonate treatment also reduced [3H]MK-801 binding, by
      modification of histidyl residues. The binding affinity was reduced to 8.3 +/-
      1.4 nM whereas the Bmax was unchanged. Protection studies indicated that the
      modified histidine is unlikely to be a component of the glutamate, glycine or MK
      801 binding sites. However, the accessibility of the modified histidine seems to
      be partly dependent on the activation of the receptor.

PMID- 8147916
TI  - Contrasting uptakes of 59Fe into spleen, liver, kidney and some other soft
      tissues in normal and hypotransferrinaemic mice. Influence of an antibody against
      the transferrin receptor.
AB  - Uptake of iron-59 from blood into various soft tissues of anaesthetized mice was
      investigated by continuous intravenous infusion of the radiotracer during 2 hr.
      The 59Fe was given either as ferrous chloride with ascorbate or as 59Fe
      transferrin. Infusions were made into adult mice with and without pretreatment
      with a monoclonal antibody against transferrin receptors, and into
      hypotransferrinaemic mice and appropriate controls. In normal mice, 59Fe uptake
      into spleen was much higher than into other tissues and was 94-96% inhibited by
      the antibody. Inhibitions due to the antibody were less complete in liver and
      renal cortex, and there was evidence of some non-transferrin-mediated transport
      during infusion of 59Fe/ascorbate. In the hypotransferrinaemic mice, tissue
      uptakes of 59Fe during infusion of 59Fe/ascorbate were enormous, being two to
      three orders of magnitude greater than in the normal controls. The rank order for
      size of uptake was liver > renal cortex > pancreas > spleen > other tissues. All
      tissues examined have a considerable potential capacity for uptake of non
      transferrin-bound iron, this being greatest in liver and renal cortex.

PMID- 8147917
TI  - Stimulation of intracellular free calcium increases by platelet-activating factor
      in HT29 colon carcinoma cells. Spectrofluorimetric and preliminary spatio
      temporal analysis using confocal laser scanning fluorescence imaging microscopy.
AB  - We examined the ability of platelet-activating factor (PAF) and its lyso
      derivative (lyso-PAF) to elicit increases in intracellular free calcium
      concentration ([Ca2+]i) in HT29 human colon carcinoma cells. Using
      spectrofluorimetric analysis with indo-1 as the [Ca2+]i reporter molecule, we
      found that 1-10 microM concentrations of both lipids stimulated substantial,
      reversible, monophasic [Ca2+]i elevations. Evidence was obtained that the two
      lipids may act via specific receptors to release Ca2+ from internal stores.
      Homologous desensitization was observed in both cases and PAF and lyso-PAF were
      also able to desensitize cells reciprocally (heterologous desensitization). The
      potent PAF receptor antagonist WEB 2086 (3-[4-(chlorophenyl)-9-methyl-6H
      thieno[3,2-f][1,2, 4]triazolo-[4,3-a][1,4]-diazepin-2-yl]-1-(4-morpholinyl)-1
      propano ne) successfully blocked PAF-induced [Ca2+]i elevations, but did not
      affect rises in response to lyso-PAF, suggesting that lyso-PAF may act through a
      different cellular receptor or mechanism. Higher concentrations (> 10 microM) of
      PAF resulted in non-reversible [Ca2+]i elevations which were caused by Ca2+
      influx following membrane lysis. However, the WEB 2086 insensitivity of these
      effects and the resultant cellular toxicity clearly showed that such events were
      mechanistically distinct from the reversible [Ca2+]i elevations apparently
      operating via WEB 2086-sensitive receptors. Preliminary spatio-temporal
      observations, using confocal microscopy and fluo-3 as the [Ca2+]i reporter
      molecule, suggested that PAF can also induce [Ca2+]i elevations in the absence of
      cell lysis in monolayer HT29 cells. Visual impressions were obtained of cellular
      and subcellular heterogeneity and of [Ca2+]i oscillations in responding cells.
      However, these need to be interpreted with caution because of the intrinsic
      limitations of the methodology, particularly using non-ratiometric dyes. The
      significance of a receptor-mediated, reversible elevation of [Ca2+]i by sub-toxic
      concentrations of PAF in HT29 colon cancer cells remains to be elucidated, but it
      is tempting to speculate that PAF might function as a locally acting signalling
      mediator in these and possibly other tumour cells.

PMID- 8147918
TI  - Increased biological activity of 20-epi-1,25-dihydroxyvitamin D3 is due to
      reduced catabolism and altered protein binding.
AB  - The 20-epi series of vitamin D3 analogs has been shown to be made up of more
      potent inducers of cell differentiation than calcitriol in vitro. Using 20-epi-1
      alpha,25-dihydroxyvitamin D3 (MC 1288), we attempted to rationalize this
      increased biological activity by examining several parameters including the
      binding affinity of the analog for the plasma binding globulin (DBP) and the
      target cell vitamin D receptor (VDR), as well as attempting to measure the rate
      at which MC 1288 is metabolized. MC 1288 was found to be metabolized 36 times
      more slowly than its epimer 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3), forming
      several metabolites which were analogous to metabolites of 1,25-(OH)2D3 formed in
      the side chain oxidation pathway. Bovine thymus VDR bound MC 1288 with five times
      greater affinity than calcitriol, while rat plasma DBP did not bind MC 1288 even
      at a concentration of 50 microM, 5000 times the B50 of 25-OH-D3, the ligand used
      in the assay. Using a vitamin D-inducible growth hormone gene reporter system we
      were able to demonstrate that MC 1288 induces human growth hormone (hGH) activity
      30-fold more efficiently than 1,25-(OH)2D3 in the presence of fetal calf serum
      (FCS), while the analog is only 10 times more efficient than 1,25-(OH)2D3 in the
      absence of FCS. We therefore conclude that MC 1288 is more biologically active
      than calcitriol in vitro due to a combination of factors: the increased VDR
      binding affinity, the decreased DBP binding affinity, and the decreased rate of
      metabolism. As with other analogs of vitamin D, the altered protein binding and
      decreased catabolism of MC 1288 may be important in pharmaceutical applications
      such as a topical treatment for psoriasis or skin cancer.

PMID- 8147919
TI  - Development of a novel method for determination of acetyl-CoA:1-alkyl-sn-glycero
      3-phosphocholine acetyltransferase activity and its application to screening for
      acetyltransferase inhibitors. Inhibition by magnolol and honokiol from Magnoliae
      cortex.
AB  - A method was developed for determining the activity of acetyl-CoA:1-alkyl-sn
      glycero-3-phosphocholine acetyltransferase (EC 2.3.1.67), a key enzyme in the
      biosynthesis of platelet-activating factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3
      phosphocholine). The assay involves measurement of the radioactivity in the
      trichloroacetic acid (TCA)-precipitated complex of radioactive product and
      albumin after incubation of 1-alkyl-sn-glycero-3-phosphocholine and [3H]acetyl
      CoA with rat spleen microsomes or membrane fractions of human polymorphonuclear
      leukocytes (PMNs). The radioactive product associated with the precipitate was
      identified as PAF using an ultrahigh-sensitivity TV camera system after
      extraction and separation by TLC. This TCA method was then used to screen the
      components of crude preparations that inhibited acetyltransferase activity. Major
      components from the cortex of Magnoliae (magnolol and honokiol), which have anti
      inflammatory and anti-bacterial actions, inhibited the acetyltransferase activity
      in rat spleen microsomes (IC50, 150 and 150 microM, respectively) and membrane
      fractions of human PMNs (IC50, 70 and 60 microM, respectively). The inhibitory
      action of magnolol and honokiol was reversible, and similar to or higher than
      that of nordihydroguaiaretic acid. PAF production in human PMNs stimulated by the
      ionophore A23187 was also suppressed dose dependently by magnolol and honokiol.
      These activities may be relevant to the claimed therapeutic effects of the
      extract from Magnoliae cortex.

PMID- 8147920
TI  - It's the patient, stupid!

PMID- 8147921
TI  - Reduced joint counts in rheumatoid arthritis clinical trials. American College of
      Rheumatology Committee on Outcome Measures in Rheumatoid Arthritis Clinical
      Trials.

PMID- 8147922
TI  - New evidence for involvement of retroviruses in Sjogren's syndrome and other
      autoimmune diseases.

PMID- 8147923
TI  - Reduced joint counts in controlled clinical trials in rheumatoid arthritis.
AB  - OBJECTIVE: To determine if quantitative assessment of a reduced number of joints
      provides information equivalent to that obtained by the traditional 60-joint
      evaluation in detecting changes in patients participating in clinical trials of
      rheumatoid arthritis (RA). METHODS: The changes in quantitative joint scores of
      patients from 3 previously reported clinical trials were compiled and compared
      with changes in quantitative scores derived using a reduced number of joints.
      Effect sizes were calculated (mean change in joint score/standard deviation of
      joint score) and compared for the different joint indices. RESULTS: The effect
      sizes of the joint scores derived using a reduced number of joints were similar
      to those of the original 60-joint score. The reduced joint count scores revealed
      significant changes for clinical trials involving as few as 15 patients.
      CONCLUSION: Reduced joint count scores may be used to evaluate the results of
      clinical trials without decreasing the ability to detect change over time.
      Quantitative assessment of a reduced number of joints may also facilitate
      assessment of responses to treatment in the routine care of patients with RA.

PMID- 8147924
TI  - Variation among rheumatologists in the use of prednisone and second-line agents
      for the treatment of rheumatoid arthritis.
AB  - OBJECTIVE: To test for and estimate variation among rheumatologists in their
      prescribing of prednisone and second-line agents for the treatment of rheumatoid
      arthritis (RA), after taking into account the characteristics of their patients.
      METHODS: Multiple logistic regression incorporating random effects for
      rheumatologists, with adjustment for patient characteristics. RESULTS: Values for
      the likelihood-ratio statistic provided strong evidence of such variation. Random
      effect variance estimates showed that the variation is of great magnitude.
      CONCLUSION: Even after patient characteristics have been taken into account, the
      data show that the rheumatologist may strongly influence the use of prednisone
      and second-line agents by a patient.

PMID- 8147926
TI  - Induction of cyclooxygenase II in human synovial microvessel endothelial cells by
      interleukin-1. Inhibition by glucocorticoids.
AB  - OBJECTIVE: To characterize the effects of interleukin-1 alpha (IL-1) on
      prostanoid biosynthesis by human rheumatoid synovium microvessel endothelium
      (HSE). METHODS: HSE cells were treated with cytokines, metabolic inhibitors, and
      steroids under various conditions, and prostaglandin biosynthesis was determined
      by radioimmunoassay. Newly synthesized cyclooxygenase (COX) was quantitated by
      immunoprecipitation of metabolically labeled HSE cell lysates. The effects of IL
      1 on levels of messenger RNA (mRNA) for COX II were also determined. RESULTS: IL
      1 induced an increase in COX activity (as assessed by prostaglandin E2 release)
      that was dose- and time-dependent and was blocked by cycloheximide, actinomycin
      D, and dexamethasone. IL-1 induced a selective increase in COX II mRNA and
      biosynthesis of COX II protein that was blocked by dexamethasone. CONCLUSION: IL
      1 treatment of HSE cells induces COX II, as demonstrated by both Northern
      blotting and immunoprecipitation. The induction of COX II expression provides, at
      least in part, a mechanism for the pronounced increase in prostanoid synthesis
      observed in HSE cells following incubation with IL-1. The selective up-regulation
      of HSE COX II by inflammatory cytokines such as IL-1 suggests that development of
      specific pharmaceutical inhibitors for this novel isozyme may provide significant
      new therapeutic advantages in the treatment of RA.

PMID- 8147925
TI  - The mortality of rheumatoid arthritis.
AB  - OBJECTIVE: To determine the risk and causes of death and to quantify mortality
      predictors in patients with rheumatoid arthritis (RA). METHODS: RA patients (n =
      3,501) from 4 centers (Saskatoon n = 905, Wichita n = 1,405, Stanford n = 886,
      and Santa Clara n = 305) were followed for up to 35 years; 922 patients died.
      RESULTS: The overall standardized mortality ratio (SMR) was 2.26 (Saskatoon 2.24,
      Wichita 1.98, Stanford 3.08, Santa Clara 2.18) and increased with time. Mortality
      was strikingly increased for specific causes: infection, lymphoproliferative
      malignancy, gastroenterologic, and RA. In addition, as an effect of the SMR of
      2.26, the expected number of deaths was increased nonspecifically across all
      causes (except cancer), with a large excess of deaths attributable to
      cardiovascular and cerebrovascular diseases. Independent predictors of mortality
      included age, education, male sex, function, rheumatoid factor, nodules,
      erythrocyte sedimentation rate, joint count, and prednisone use. CONCLUSION:
      Mortality rates are increased at least 2-fold in RA, and are linked to clinical
      severity.

PMID- 8147927
TI  - Association of TAP2 polymorphism with rheumatoid arthritis is secondary to
      allelic association with HLA-DRB1.
AB  - OBJECTIVE: To study polymorphisms of the newly described TAP2 locus in rheumatoid
      arthritis (RA) and to analyze their relationship with HLA-DRB1 alleles previously
      implicated in the development of the disease. METHODS: TAP2 polymorphic residues
      at 3 sites, Val/Ile-379, Ala/Thr-565, and Ala/Thr-665, were characterized by
      amplification refractory mutation system polymerase chain reaction in 185 RA
      patients and 48 HLA-DR4 positive healthy controls. HLA-DR4 subtypes were
      determined by sequence-specific priming and oligonucleotide hybridization.
      RESULTS: The frequencies of Ile-379, Thr-565, and Thr-665 were significantly
      increased in DR4 positive versus DR4 negative RA patients. TAP2 genotype
      distributions also differed between the patient groups stratified by DR4 status.
      However, no significant differences in TAP2 polymorphisms were observed between
      DR4 positive RA patients and DR4 positive controls, although relationships
      between specific DR4 subtypes and TAP2 variants were identified. CONCLUSION:
      Particular TAP2 polymorphisms are associated with distinct HLA-DR specificities
      in both normal and RA populations. Thus, the prevalence of specific TAP2 residues
      and genotypes in RA appears to be secondary to the HLA-DR frequencies and
      genotypic combinations that are typical of RA.

PMID- 8147928
TI  - HLA-DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid
      arthritis.
AB  - OBJECTIVE: Immunogenetic analysis has demonstrated that giant cell arteritis
      (GCA) and rheumatoid arthritis (RA) are associated with 2 different domains of
      the HLA-DR4 molecule. The present study was undertaken to evaluate whether
      polymyalgia rheumatica (PMR) immunogenetically resembles GCA or RA and to
      determine whether expression of HLA-DRB1 alleles can be used to detect
      heterogeneity among PMR patients. METHODS: Forty-six patients with PMR, 52 with
      GCA, 122 with seropositive RA, and 72 normal individuals were genotyped for HLA
      DRB1 alleles by allele-specific amplification and subsequent oligonucleotide
      hybridization. RESULTS: The HLA-DRB1*04 allele was the most frequent among PMR
      patients (67%). While the expression of allelic variants of the HLA-DR4 family
      was restricted to HLA-DRB1*0401 and *0404/8 in RA patients, all HLA-DRB1*04
      alleles, including B1*0402 and B1*0403, were represented in the PMR group. The
      distribution of HLA-DRB1 alleles among HLA-DRB1*04 negative patients was similar
      in those with PMR and those with GCA, and could be distinguished from that in RA
      patients. In particular, HLA-DRB1*01 alleles, which were found in most HLA
      DRB1*04 negative RA patients, were underrepresented in patients with PMR and GCA.
      CONCLUSION: The distribution of HLA-DRB1 alleles in PMR resembles that found in
      GCA. PMR and GCA share the associated sequence polymorphism encoded by the second
      hypervariable region (HVR) of the HLA-DRB1 gene. The HLA-DRB1 association of PMR
      and GCA can be distinguished from that of RA, which is linked to a sequence motif
      in the third HVR of DRB1 alleles. The differential role of distinct domains on
      HLA-DR molecules suggests that multiple biologic functions are regulated by these
      molecules and that they contribute differently to disease mechanisms. The
      similarities in the distribution of HLA-DRB1 alleles in PMR and GCA indicates
      that HLA-DRB1 alleles are not predictive for progression of PMR to the vasculitic
      lesions that are pathognomonic for GCA.

PMID- 8147929
TI  - Intraarticular injections of hyaluronan in patients with cartilage abnormalities
      and knee pain. A one-year double-blind, placebo-controlled study.
AB  - OBJECTIVE: To compare the effect of intraarticular injections of hyaluronan and
      placebo (vehicle, saline) in patients with knee pain on exertion and with joint
      cartilage abnormalities. METHODS: Fifty-two patients with arthroscopically
      verified deep cartilage fissures and villus-like flakes in the symptomatic knee
      were randomly assigned to receive intraarticular injections of 2.5 ml of either
      hyaluronan or vehicle, weekly for 5 weeks. The effect was evaluated by both
      primary and secondary parameters of efficacy at 2, 4, 13, 26, and 52 weeks.
      RESULTS: At the followup visits, both groups had improvement from baseline;
      however, there was no difference between the groups in any of the relevant
      variables at any time point. CONCLUSION: The effects of intraarticular hyaluronan
      do not differ significantly from those of placebo in patients with knee pain and
      cartilage disease.

PMID- 8147930
TI  - Diacerhein in the treatment of osteoarthritis of the hip.
AB  - OBJECTIVE: To determine the efficacy and safety of diacerhein, a potential new
      therapeutic agent with properties differing from those of existing nonsteroidal
      anti-inflammatory drugs (NSAIDs), and of a combination of diacerhein and an NSAID
      (tenoxicam) in the treatment of osteoarthritis (OA) of the hip. METHODS: Two
      hundred eighty-eight patients with painful OA of the hip were enrolled in an 8
      week randomized, double-blind, placebo-controlled, 2 x 2 factorial design study.
      Four treatment groups were defined: 1) diacerhein placebo and tenoxicam placebo,
      2) tenoxicam and diacerhein placebo, 3) diacerhein and tenoxicam placebo, and 4)
      diacerhein and tenoxicam. The daily dosages of diacerhein and tenoxicam were 100
      mg and 20 mg, respectively. RESULTS: Analyses of efficacy showed no interaction
      between diacerhein and tenoxicam in terms of efficacy, a clinically significant
      rapid (< or = 2 weeks) and persisting effect of tenoxicam during the 8 weeks of
      the study, and a slow-acting (6 weeks) effect of diacerhein. Moderate, transient
      diarrhea was the most frequent side effect observed in the diacerhein group (37%)
      compared with the placebo group (4%). CONCLUSION: Both tenoxicam and diacerhein
      appear to be superior to placebo, and neither agent appears to significantly
      enhance or detract from the efficacy of the other when they are administered
      concomitantly. The onset of action of diacerhein appears to be delayed (> or = 4
      weeks).

PMID- 8147931
TI  - Integrin expression by human articular chondrocytes.
AB  - OBJECTIVE: To perform a comprehensive analysis of the integrin forms expressed by
      normal human articular chondrocytes. METHODS: Cartilage sections and collagenase
      released chondrocytes were probed with a comprehensive panel of integrin isoform
      specific monoclonal antibodies (MAb), using in situ immunohistochemistry
      techniques, indirect immunofluorescence and flow cytometry, and
      immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). RESULTS: Chondrocytes in cartilage sections reacted with MAb specific
      for the alpha 5, alpha v, and beta 1 integrin subunits and the alpha v beta 3 and
      alpha v beta 5 heterodimers. They also reacted with a polyclonal antibody
      specific for the intracytoplasmic portion of the alpha 1 subunit. MAb specific
      for the alpha v subunit reacted more strongly with chondrocytes near the
      articular surface than with those in deeper layers of cartilage, and the alpha v
      beta 3-specific MAb reacted exclusively with chondrocytes within the most
      superficial 30 microns of cartilage. Flow cytometric analysis and SDS-PAGE
      analysis of immunoprecipitates prepared from extracts of cell-surface
      radioiodinated chondrocytes confirmed the above observations, and additionally
      revealed the presence of the alpha 3 beta 1 integrin. CONCLUSION: Normal human
      articular chondrocytes prominently display substantial quantities of the alpha 1
      beta 1, alpha 5 beta 1, and alpha v beta 5 integrin heterodimers, as well as
      lesser quantities of the alpha 3 beta 1 and alpha v beta 3 heterodimers. The
      alpha v subunit-containing integrins are detected more readily on the more
      superficial chondrocytes than on chondrocytes deep within cartilage. These
      observations provide the basis for analysis of the role of chondrocyte integrins
      in cartilage homeostasis and in the pathogenesis of joint diseases.

PMID- 8147932
TI  - Expression of sequences homologous to HTLV-I tax gene in the labial salivary
      glands of Japanese patients with Sjogren's syndrome.
AB  - OBJECTIVE: 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).
      METHODS: 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 reverse transcription and polymerase chain reaction techniques.
      RESULTS: 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. 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- 8147933
TI  - Effect of low-dose cyclosporin A on systemic lupus erythematosus disease
      activity.
AB  - OBJECTIVE: To determine the effect of low-dose cyclosporin A (CSA) treatment on
      disease activity in systemic lupus erythematosus (SLE). METHODS: All patients in
      the study had active disease as defined by at least the presence of a low CH50
      level. Patients were initially given 3 mg/kg/day of CSA. Dosages were adjusted
      individually at every visit, according to both clinical and laboratory data.
      RESULTS: Eleven women with SLE were enrolled in the study; 10 were evaluable.
      After 20 weeks of CSA treatment, the mean score for disease activity on the SLE
      Disease Activity Index decreased significantly, from 10.6 to 3.8 (P = 0.02). The
      titer of antinuclear antibodies decreased in 8 patients and the level of anti-DNA
      antibodies decreased in 5. Side effects included hypertension (40%),
      hypertrichosis (30%), gingival hypertrophy (10%), and a rise in the blood urea
      nitrogen level. Serum creatinine levels remained unchanged. CONCLUSION: The
      favorable responses observed in our patients strongly suggest that low-dose CSA
      can reduce the disease activity of SLE.

PMID- 8147934
TI  - Kidney biopsy in systemic lupus erythematosus. III. Survival analysis controlling
      for clinical and laboratory variables.
AB  - OBJECTIVE: To examine the importance of renal biopsy as a predictor of death due
      to any cause in patients with systemic lupus erythematosus (SLE). METHODS: The
      study included 123 SLE patients who had a renal biopsy between 1970 and 1984 and
      were followed up as part of a prospective study. Data were initially analyzed to
      identify clinical and laboratory features that were significantly associated with
      the risk of dying. Renal biopsy variables were then examined to determine whether
      they contributed additional information about prognosis. RESULTS: The clinical
      and laboratory factors most closely associated with the risk of dying in
      multivariate analyses were the serum creatinine level and the SLE Disease
      Activity Index score. The presence of chronic renal lesions on biopsy contributed
      significantly to the prognostic information offered by clinical and laboratory
      factors in the subset of patients who had normal serum creatinine levels--the
      majority (85%) of patients in this study. CONCLUSION: These results indicate that
      renal biopsy serves an important role in the assessment of prognosis in patients
      who do not have advanced renal disease.

PMID- 8147935
TI  - Association between antiphospholipid antibodies and epilepsy in patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether the occurrence of seizures is correlated with the
      presence of serum antiphospholipid antibodies (aPL) in systemic lupus
      erythematosus (SLE) patients. METHODS: The study included 221 unselected patients
      with SLE. Of these, 21 patients with epileptic seizures not attributed to any
      cause other than SLE were identified. Epilepsy was diagnosed by clinical history
      and electroencephalography. Blood samples were tested for the presence of
      antibodies to cardiolipin (aCL, IgG and IgM isotypes) and lupus anticoagulant
      (LAC). RESULTS: LAC was detected in 43.8% of the patients with epilepsy and in
      20.8% of controls (P = 0.057). A statistically significant association was found
      between moderate-to-high titers of IgG aCL and the presence of seizures (P =
      0.02). Brain computed tomography and/or magnetic resonance imaging scanning was
      performed in 14 patients. All patients with abnormal features found on these
      tests had positive aPL (P = 0.03). Nine patients (42.9%) had at least 1 of the
      classic features associated with the aPL syndrome. CONCLUSION: We confirmed that
      epilepsy as a primary neuropsychiatric event is significantly associated with
      moderate-to-high titers of IgG aCL in SLE patients. Our results suggest that aPL
      could have a role in the etiopathogenesis of epilepsy in SLE.

PMID- 8147936
TI  - Serum thrombomodulin. A novel marker of disease activity in systemic lupus
      erythematosus.
AB  - OBJECTIVE: Soluble thrombomodulin (sTM), a proposed serum marker of endothelial
      cell injury, was investigated as a parameter of disease activity in patients with
      systemic lupus erythematosus (SLE). METHODS: Levels of sTM were determined by
      enzyme-linked immunosorbent assay. Disease activity was assessed using 3
      established scoring systems: the American College of Rheumatology (ACR), the New
      York Hospital for Special Surgery (NYHSS), and the Systemic Lupus Activity
      Measure (SLAM) systems. RESULTS: A close correlation was found between sTM levels
      and disease activity as assessed with all 3 scoring systems: r = 0.52 by the ACR,
      0.75 by the NYHSS, and 0.82 by the SLAM. CONCLUSION: We found that sTM is a
      sensitive serologic marker of organ involvement in patients with SLE.
      Furthermore, sTM may prove to be an important marker for vasculitis in general.

PMID- 8147937
TI  - Determination of the blood lactate:pyruvate ratio as a noninvasive test for the
      diagnosis of zidovudine myopathy.
AB  - OBJECTIVE: To evaluate the use of the lactate: pyruvate ratio as a test for the
      detection of zidovudine myopathy. METHODS: Twenty consecutive human
      immunodeficiency virus-infected patients with muscle involvement and 20 without
      muscle involvement were studied prospectively. Blood lactate and pyruvate levels
      and serum creatine kinase levels were tested, muscle involvement was assessed
      both clinically and electrophysiologically, and muscle biopsy was performed in
      patients with myopathy. RESULTS: Nine patients had biopsy-proven zidovudine
      myopathy. All 9 had a high lactate:pyruvate ratio, with elevations on 2 of 2
      determinations in 6 patients and on 1 of 2 in 3 patients. Two of 11 patients with
      other myopathies and 2 of 20 patients without myopathy had a high
      lactate:pyruvate ratio on 1 of 2 determinations. CONCLUSION: The lactate:pyruvate
      ratio, when determined repeatedly, is a sensitive test for detecting
      mitochondrial muscular toxicity of zidovudine.

PMID- 8147938
TI  - Reduction of mortality and lymphadenopathy in MRL-lpr/lpr mice treated with
      nonmitogenic anti-CD3 monoclonal antibody.
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of nonmitogenic anti-CD3
      monoclonal antibody (MAb) in a preexisting autoaggressive response, using the MRL
      lpr/lpr (MRL/l) murine model of autoimmune disease. METHODS: Female MRL/l mice, 8
      10 weeks of age, were treated with nonmitogenic anti-CD3 MAb or phosphate
      buffered saline and effects on mortality, lymphadenopathy, T cell phenotypes,
      anti-DNA titers, and total IgG titers were measured. RESULTS: Nonmitogenic anti
      CD3 MAb treatment resulted in a dramatic reduction in lymphadenopathy and
      mortality, as well as an early reduction in alpha/beta+, CD4-, CD8-, Thy+, B220+
      (double-negative) lymph node cells. No significant effects on anti-DNA or IgG
      titers were observed. No morbidity was observed following administration of
      nonmitogenic anti-CD3 MAb. CONCLUSION: A short course of treatment with
      nonmitogenic anti-CD3 MAb can suppress preexisting autoimmune responses without
      inducing the cytokine-mediated toxicity characteristic of mitogenic forms of anti
      CD3 MAb. The use of nonmitogenic anti-CD3 MAb may be efficacious in the clinical
      setting for the treatment of T cell-mediated autoimmune disorders.

PMID- 8147939
TI  - Relationship between antineutrophil cytoplasmic antibody levels and disease
      activity in Wegener's granulomatosis: comment on the article by Kerr et al.

PMID- 8147940
TI  - The effects of methotrexate on soluble interleukin-2 receptor levels in
      rheumatoid arthritis: comment on the article by Barrera et al.

PMID- 8147941
TI  - Stereoselective differences in the binding of N-methylated barbiturates to human
      serum albumin.
AB  - The binding to human serum albumin (HSA) of a homologous series of N-methylated
      chiral barbiturates was studied by means of equilibrium dialysis. The length of
      the aliphatic side chain at C-5 of the barbiturate ring was variable, and the
      compounds used were: (+)-(S)- and (-)-(R)-5-methyl-(A), -5-ethyl-(B), -5-propyl
      (C) and -5-butyl-(D)-1-methyl-5-phenyl-barbiturate. Binding parameters (numbers
      of binding classes and of binding sites in each class, affinity constant, total
      binding constant) were obtained from the Scatchard plot of the percent binding
      values. For both enantiomers of A and D as well as for (-)-(R)-B 2 classes were
      obtained; (+)-(S)-B and both enantiomers of C had only 1 class. The total binding
      constant (K) indicated a more than twofold higher binding of (-)-(R)-B (2.64 x
      10(3).mol-1) and C (5.75 x 10(3).mol-1) compared with the corresponding (+)-(S)
      enantiomer (1.02 and 2.00 x 10(3).mol-1, respectively); in the case of D the (+)
      (S)-enantiomer was preferentially bound (K = 10.14 vs. 5.40 x 10(3).mol-1 for the
      (-)-(R)-enantiomer). The percent binding values of (+)-(S)-A were higher than
      those of (-)-(R)-A; however, the K-values of the A-enantiomers were almost
      identical.

PMID- 8147942
TI  - [Absolute bioavailability of chlorpromazine, promazine and promethazine].
AB  - The absolute bioavailability of the three phenothiazine neuroleptics, promazine
      (Sinophenin, CAS 58-40-2), chlorpromazine (Propaphenin, CAS 50-53-3) and
      promethazine (Prothazin, CAS 60-87-7) was tested in three single-dose cross-over
      studies. In each trial 12 to 14 healthy volunteers were enrolled. The single
      doses for promazine, promethazine and chlorpromazine were 100, 75 and 150 mg
      (orally) and 20, 50 and 50 mg (intravenously), resp. The serum concentrations of
      the three neuroleptics were measured by means of a selective HPLC-method. the
      distribution-free confidence intervals for the absolute bioavailability of the
      three phenothiazines were within 10.5 to 24.7% for chlorpromazine, 7.8 to 24.9%
      for promazine and 12.3 to 40% for promethazine. Promazine and chlorpromazine are
      pharmacokinetically very similar and differ substantially from promethazine.

PMID- 8147943
TI  - Taurine and myocardial noradrenaline.
AB  - Taurine (CAS 107-35-17) is an anticonvulsant used also as an adjunct in the
      treatment of cardiovascular disorders. Therefore, we studied its effects
      noradrenergic transmission in the isolated rabbit heart prelabelled with 3H
      noradrenaline. At the concentrations of 1 and 10 mmol/l taurine treatment was
      without effect on the neuronal and extraneuronal uptake of noradrenaline by the
      myocardial tissue. At the highest concentration, it decreased the spontaneous
      release of the transmitter and enhanced its catabolism. Without any significant
      effect on tyramine-induced noradrenaline release, taurine decreased the release
      of the amine induced by dimethylphenylpiperazinium and nerve stimulation. These
      results suggested that taurine may reduce the peripheral sympathetic activity by
      accelerating noradrenaline catabolism and decreasing its release probably via its
      ability to prevent a rise of intracellular calcium ion.

PMID- 8147944
TI  - Radioautographic study of benidipine hydrochloride. Localization in the
      mesenteric artery of spontaneously hypertensive rat.
AB  - Microradioautographic study of [3H]-benidipine hydrochloride (KW-3049, CAS 91599
      74-5) and nitrendipine (CAS 39562-70-4) localization was performed in the
      supramesenteric arteries of the spontaneously hypertensive rats (SHR) at 10 and
      30 min after intravenous administration or in vitro incubation. The distribution
      of silver grains was observed by light and electron microscopy and the number of
      grains was counted in the tunicae intima, media and adventitia of the arteries.
      Areas of the correlated part of the artery were measured and the grain count per
      area was calculated. The grain count of [3H]-benidipine hydrochloride showed
      almost uniform distribution in the tunicae intima and media, which was compared
      at 10 and 30 min after the administration both in the in vivo and in the in vitro
      studies. The grain density of [3H]-nitrendipine to the tunicae intima and media
      increased time-dependently. Electron microscopic observation revealed that the
      fine distribution of [3H]-benidipine hydrochloride was mainly localized on the
      plasma membrane and on the cytoplasm of the cellular components of the mesenteric
      artery. The result suggested that the distribution of [3H]-benidipine
      hydrochloride was related to its pharmacologically active site, i.e. plasma
      membrane of the tunica intima and the smooth muscle cells of the tunica media.

PMID- 8147945
TI  - Antihypertensive efficacy of a slow release nifedipine tablet formulation given
      once daily in patients with mild to moderate hypertension. A placebo-controlled,
      double-blind parallel-group trial.
AB  - In a double-blind, randomized parallel-group, multi-center study the
      antihypertensive efficacy of a slow release tablet containing 60 mg nifedipine
      (Aprical long, CAS 21829-25-4) has been investigated. After two-weeks wash-out of
      previous antihypertensive medication and a two-weeks placebo run-in period, 88
      patients of both gender with a diastolic blood pressure between 95 and 115 mmHg
      received either nifedipine or placebo for 8 weeks. Blood pressure was measured at
      the end of the dose interval at rest by a semi-automatic, auscultatory device.
      Control measurements were recorded using a standard cuff sphygmomanometer.
      Primary efficacy criterion was the drop in diastolic blood pressure (DBP,
      measured semi-automatically) after 8 weeks therapy. 88 patients were randomized
      to nifedipine or placebo. 86 patients completed the protocol (42 nifedipine, 44
      placebo). However, only in 73 patients BP measurements were recorded
      appropriately with the semi-automatic device (36 nifedipine, 37 placebo). In the
      nifedipine group, blood pressure fell from 152 (+/- 18)/102 (+/- 6) mmHg to 139
      (+/- 16)/91 (+/- 10) mmHg. Blood pressure under placebo was determined to 149 (+/
      20)/102 (+/- 8) mmHg before treatment and 146 (+/- 18)/100 (+/- 10) mmHg at the
      end of the study. Heart rate was not affected under both treatments. The 90%
      confidence interval of the difference between the mean fall in DBP ranged from
      5.0 to 12.5 mmHg, the point estimator was 8.8 mmHg. At the end of the study, 21
      of 36 patients under nifedipine and 10 of 37 patients under placebo had a DBP
      below 90 mmHg and/or a decrease in DBP > 10 mmHg.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8147946
TI  - Study on the acceleration in healing of ethanol-induced gastric lesions in rats
      by methylprednisolone.
AB  - This study was designed to determine the influences of methylprednisolone (MP,
      CAS 2375-03-3) on the genesis and healing of gastric lesions induced by 50%
      ethanol in relation to the changes in gastric mucosal prostaglandin (PG) and
      leukotriene (LT) contents and vascular permeability. Intragastric administration
      of 1 ml of 50% ethanol induced hemorrhagic lesions in the fundic portion, and
      these lesions were not affected by 20 mg/kg of MP injected subcutaneously 30 min
      before ethanol administration. In untreated rats, 4 kinds of PGs, i.e., 6-keto
      PGF1a, PGF2a, PGE2, and PGD2, were determined in gastric mucosa by high
      performance liquid chromatography (HPLC), but no LTs were detected.
      Administration of ethanol significantly reduced all PG contents and increased
      production of peptide-LTs in gastric mucosa. Pretreatment with MP did not
      influence ethanol-induced changes in PG and peptide-LT contents. Ethanol-induced
      lesions required 96 h for total healing. Ulcer healing was not affected by MP,
      which was injected subcutaneously twice daily from 1 h after ethanol
      administration until the end of the experiment, and complete ulcer healing was
      observed after 72 h. MP did not affect ethanol-induced decrease in PG contents,
      their recoveries, or peptide-LT contents. Ethanol increased vascular permeability
      and MP reduced this increase. These results suggest that MP does not have a
      hazardous effect, but is rather beneficial with regard to healing of ethanol
      induced gastric lesions through prevention of the increase in vascular
      permeability caused by ethanol, and that it affected neither gastric mucosal PG
      nor peptide-LT contents.

PMID- 8147947
TI  - Effects of treatment with bezafibrate on lipoprotein lipase activity and mass in
      patients with hypertriglyceridemia.
AB  - The activity and mass of lipoprotein lipase (LPL) in postheparin plasma (PHP)
      from patients with hypertriglyceridemia coupled with hypertension, impaired
      glucose tolerance, hyperinsulinemia were investigated in order to clarify the
      cause of hypertriglyceridemia and the effects of bezafibrate (CAS 41859-67-0), a
      novel lipid lowering agent. Eight weeks of treatment with bezafibrate (200 mg/d)
      lowered plasma total cholesterol and triglyceride by 7 and 39%, respectively, and
      increased plasma high density lipoprotein (HDL) cholesterol by 23% in the
      patients (n = 15). The LPL activity and mass of PHP in the patients were found to
      be lower than in the normal controls. The LPL activity and mass of PHP in the
      patients before treatment with bezafibrate (n = 15) were 2.05 +/- 1.06 mumol/ml/h
      and 147 +/- 45 ng/ml, respectively, whereas after treatment with 200 mg/d of
      bezafibrate for 8 weeks, these values were 3.62 +/- 1.30 mumol/ml/h (p < 0.01)
      and 226 +/- 57 ng/ml (p < 0.05), respectively. The increases of LPL mass were
      positively correlated with the decrease of triglyceride levels during the same
      period. These results suggest that the expression of LPL enzyme protein is
      impaired in patients with hypertriglyceridemia coupled with hypertension,
      impaired glucose tolerance and hyperinsulinemia, and the impaired expression of
      LPL recovers during treatment with bezafibrate, resulting in improvement of
      hypertriglyceridemia.

PMID- 8147948
TI  - Antitussive effects of levodropropizine in the dog.
AB  - The antitussive activity of levodropropizine (S(-)3-(4-phenyl-piperazine-1-yl)
      propane-1,2-diol, DF 526, CAS 99291-25-5) was evaluated after oral administration
      to the conscious dog. Levodropropizine had a good antitussive activity,
      comparable with, but having a longer duration of action than dropropizine, the
      racemate from which it is derived. The antitussive activity of levodropropizine
      in the dog was approximately 1/20 of that of codeine phosphate.

PMID- 8147949
TI  - Synthesis of 7-substituted-4-(3',4',5'-trisubstituted-1-pyrazolyl)pyramido-[5,4
      c] cinnolines and their anti-inflammatory activities.
AB  - Eight title compounds were synthesised from substituted anelines. All compounds
      were tested for inhibition of bovine serum albumin denaturation. Few selected
      compounds were studied for their ability to provide protection against
      carrageenin-induced edema in rat paw and to inhibit denaturation of bovine serum
      albumin in an attempt to elucidate their cellular mechanism of action. There was
      no relationship between anti-inflammatory activity of 7-substituted-4-(3',4',5'
      trisubstituted-1-pyrazolyl)pyrimido[5,4- c] cinnolines and their bovine serum
      albumin denaturation effectiveness.

PMID- 8147950
TI  - Binding of sulindac to human serum albumin studied by circular dichroism.
AB  - The protein binding of sulindac (CAS 38194-50-2) was studied using circular
      dichroism (CD). By the new algorithm for the analysis of proposed data the
      association constants (k) and number of binding sites (N) were determined. The
      binding was found to go through separate stages, where the binding affinity tends
      to become lower; the first step characterized by kI = 7.6 x 10(6) l.mol-1 and NI
      = 1.4; while for the second step kII = 1.7 x 10(6) l.mol-1 and NII = 6.6. On the
      basis of the CD-data and using UV-spectra the nature of binding sites was
      studied. It may be stated that the binding sites are situated in the region of
      asymmetrically perturbed chromophore of the drug, which made a positive
      contribution to the Cotton effect. The results obtained suggest a mechanism of
      interaction which is consistent with the stepwise binding model.

PMID- 8147951
TI  - Anti-inflammatory activity of rolipram in a rat ear edema model.
AB  - In the present study the anti-inflammatory activity of the phosphodiesterase
      inhibitor rolipram (ZK 62,711, CAS 61413-54-5) was tested in a rat model where
      edema was induced in the ears of the animals by the epicutaneous application of
      croton oil in ethanol (5%, by volume). The administration of 0.015, 0.15 and 1.5
      mg rolipram per ear dose-dependently inhibited the formation of edema.
      Concomitantly, the body temperature of the rats was decreased. 4-14% of rolipram
      was percutaneously absorbed within a 5-h interval. The absorbed proportion,
      represented by the area under the plasma level-time curve, correlated with the
      inhibition of edema formation and with the decrease in body temperature.

PMID- 8147952
TI  - Synthesis and biological studies on some organo-tin and lead halo and mixed halo
      pseudohalo anionic complexes.
AB  - Some new anionic complexes of organo-tin(IV) and lead (IV) isolated in
      combination of tetraorgano-ammonium phosphonium and stibonium cation(s). L[R4
      nMXnY] and L2[R2MX2Y2], where R = C2H5, C4H9 or C6H5; M = Sn or Pb; X = Y = Cl =
      Br, I, N3, NCS; n = 1, 2 and L = R4M1 (M1 = N, P, Sb), whose structures were
      confirmed by correct elemental analyses, molar conductance values, van't Hoff
      factor and IR spectral studies, were synthesized and evaluated for anti
      convulsant activity in vivo and antiviral and antibacterial activity in vitro. A
      few of them exhibited promising activity. In addition, the toxicity (ALD50) and
      effects on the central nervous system of these complexes have been studied in
      mice.

PMID- 8147953
TI  - Efficacy and quality in clinical trials. Requirements to the investigator site.
      European Economic Community.
AB  - Guidelines and recommendations to conduct clinical trials have been defined for
      Europe since 1st July 1991 to ensure high quality standards. Thus, cost and speed
      of clinical trials are becoming more and more important in clinical research. The
      article tries to summarize specific requirements to the investigator site
      considering the aspects of quality and data evaluation. Furtheron a model is
      proposed to optimize realization of clinical trials in hospital institutions.
      Realization of "Good Clinical practice" (GCP) at the sponsor and the investigator
      site will improve the quality of clinical trials for the sake of the patients and
      finally leads to the acceptance of European clinical trials abroad.

PMID- 8147954
TI  - A solvent I detergent treated, pasteurised and highly purified factor VIII
      concentrate.
AB  - In an assessment of the risks of virus transmission by clotting concentrates it
      is clear that the currently practised procedures for virus inactivation are not
      equally effective against all types of viruses; neither a pasteurisation nor the
      solvent detergent (SID) process alone are adequate enough to inactivate viruses
      that are strongly resistant to heat and organic solvents. In this context, human
      parvovirus B19 and hepatitis A virus (HAV) are of particular concern. In order to
      improve this situation which still poses a risk to the haemophiliac patients, a
      more effective pasteurisation process has been developed that could be easily
      applied to an already well established factor VIII (FVIII) process in addition to
      the SID-treatment. Experiments using temperatures above 60 degrees C were
      performed prompted by two recent publications, which demonstrate that HAV becomes
      instable at temperatures exceeding 62 degrees C. It is the purpose of this paper
      to present the following progress: achievement of a pasteurisation procedure for
      FVIII at 63 degrees C for 10 h with no discernible change in the structure of the
      factor VIII/von Willebrand factor (FVIII/VWF) complex owing to a newly developed
      composition of stabilizers; application of this pasteurisation procedure to a
      purified FVIII fraction that has already been submitted to a SID-treatment: Doing
      so, two independent virus inactivation steps are performed as previously
      recommended by the International Association of Biological Standardization
      (IABS). Introduction of a second purification step on an anion exchange resin,
      achieving an additional virus reduction over the presently manufactured FVIII
      preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8147955
TI  - The assessment of speech-related attitudes and beliefs of people who stutter.

PMID- 8147956
TI  - [Intracavernous injections in erection disorders].

PMID- 8147957
TI  - Correction of micrognathia with ankylosis of the temporomandibular joint in
      childhood.
AB  - Insult of temporomandibular joints in infancy may result in severe micrognathia
      with ankylosis. These patients require tracheostomy and a pureed diet for
      survival. Between July of 1987 and December of 1990, we treated eight patients
      with severe micrognathia and ankylosis of one or both temporomandibular joints.
      Preoperative range of motion at the central incisors was 3.2 +/- 2.1 mm (mean +/-
      SD). Patients underwent functional reconstruction of one (n = 3) or both (n = 5)
      temporomandibular joints using costochondral grafts and mandibular advancement at
      10.4 +/- 1.7 years of age (mean +/- SD). Rigid fixation of bone grafts with early
      remobilization was achieved in all cases. Average mandibular advancement was 23.8
      +/- 3.7 mm (mean +/- SD), and average elongation was 21.4 +/- 3.3 mm (mean +/-
      SD). Range of motion at the central incisors was 27.4 +/- 4.2 mm (mean +/- SD)
      1.7 +/- 0.8 years (mean +/- SD) postoperatively. Seven patients had
      tracheostomies prior to surgery, and all were successfully decannulated within 6
      months postoperatively. One patient was treated with closed capsulotomy under
      general anesthesia. Two were treated with open capsulotomy and fascial flap
      transposition. Functional reconstruction of this deformity in mixed dentition
      offers these unfortunate individuals significant predictable improvement.

PMID- 8147958
TI  - From lymphodrek to interleukin 1 (IL-1)

PMID- 8147959
TI  - Morbidity and mortality in hypertensive adults with a low ankle/arm blood
      pressure index.
AB  - OBJECTIVE: To evaluate the relationship between the ankle/arm blood pressure
      index (AAI, the ratio of ankle to arm systolic blood pressure, a measure of
      peripheral arterial disease) and short-term cardiovascular morbidity and
      mortality in older adults with systolic hypertension. DESIGN: Prospective cohort
      study, 1- to 2-year follow-up (mean, 16 months). SETTING: Eleven of 16 field
      centers from the Systolic Hypertension in the Elderly Program. PARTICIPANTS: 1537
      older men and women with systolic hypertension. MAIN OUTCOME MEASURES: All-cause
      mortality, coronary heart disease (CHD) mortality, cardiovascular disease (CVD)
      mortality, and CHD and CVD morbidity and mortality. RESULTS: The AAI was measured
      at the 1989-1990 clinic examination and was 0.9 or less in 25.5% of 1537
      participants. A low AAI was associated with most major CHD and CVD risk factors.
      In those with a low AAI (< or = 0.9) compared with those with an AAI of more than
      0.9, age- and sex-adjusted relative risks for mortality end points at follow-up
      were as follows: total mortality, 3.8 (95% confidence interval [CI], 2.1 to 6.9);
      CHD mortality, 3.24 (95% CI, 1.4 to 7.5); and CVD mortality, 3.7 (95% CI, 1.8 to
      7.7). For CVD morbidity and mortality, the age- and sex-adjusted relative risk
      was 2.5 (95% CI, 1.5 to 4.3). After adjustment for baseline CVD and other
      cardiovascular risk factors, the relative risk for total mortality was 4.1 (95%
      CI, 2.0 to 8.3) and for CVD morbidity and mortality, 2.4 (95% CI, 1.3 to 4.4).
      Results were similar when participants with clinical CVD at baseline were
      excluded. CONCLUSION: A low AAI appears to be an important predictor of morbidity
      and mortality among older adults with systolic hypertension.

PMID- 8147960
TI  - The effect of long-term intensified insulin treatment on the development of
      microvascular complications of diabetes mellitus.
AB  - BACKGROUND: A cause-and-effect relation between blood glucose concentrations and
      microvascular complications in patients with insulin-dependent diabetes mellitus
      has not been established. METHODS: We randomly assigned 102 patients with insulin
      dependent diabetes mellitus, nonproliferative retinopathy, normal serum
      creatinine concentrations, and unsatisfactory blood glucose control to
      intensified insulin treatment (48 patients) or standard insulin treatment (54
      patients). We then evaluated them for microvascular complications after 18 months
      and 3, 5, and 7.5 years. RESULTS: Mean (+/- SD) glycosylated hemoglobin values
      were reduced from 9.5 +/- 1.3 percent to 7.1 +/- 0.7 percent in the group
      receiving intensified treatment and from 9.4 +/- 1.4 percent to 8.5 +/- 0.7
      percent in the group receiving standard treatment (P = 0.001). In 12 of the
      patients receiving intensified treatment (27 percent of those included in the
      analysis) and 27 of those receiving standard treatment (52 percent), serious
      retinopathy requiring photocoagulation developed (P = 0.01). Visual acuity
      decreased in 6 patients receiving intensified treatment (14 percent) and in 18
      receiving standard treatment (35 percent) (P = 0.02). Nephropathy (urinary
      albumin excretion, > 200 micrograms per minute) developed in one patient in the
      group receiving intensified treatment, as compared with nine patients in the
      group receiving standard treatment (P = 0.01). No patient in the intensified
      treatment group had nephropathy with subnormal glomerular filtration rates, as
      compared with six patients in the standard-treatment group (P = 0.02). The
      conduction velocities of the ulnar, tibial, peroneal, and sural nerves decreased
      significantly more in the standard-treatment group than in the intensified
      treatment group. The odds ratio for serious retinopathy was 0.4 (95 percent
      confidence interval, 0.2 to 1.0; P = 0.04) in the intensified-treatment group as
      compared with the standard-treatment group. The corresponding odds ratio for
      nephropathy was 0.1 (95 percent confidence interval, 0 to 0.8; P = 0.04).
      CONCLUSIONS: Long-term intensified insulin treatment, as compared with standard
      treatment, retards the development of microvascular complications in patients
      with insulin-dependent diabetes mellitus.

PMID- 8147961
TI  - Lymphocyte responsiveness of children supplemented with vitamin A and zinc.
AB  - We sought to determine the effect of supplementation with zinc, vitamin A, or a
      combination of the two on proliferation of T lymphocytes to concanavalin A
      (ConA), tetanus toxoid (TT), or tuberculin (PPD) of children living in a region
      endemic for suboptimal vitamin A and zinc intake. The children (n = 140, aged 6
      13 y) were randomly assigned and supplemented with either zinc (25 mg/d), vitamin
      A (1500 mg RE/d), zinc + vitamin A, or placebo for 6 mo. After a baseline blood
      collection, subjects were boosted with diphtheria-tetanus antigen. Proliferative
      responsiveness of T lymphocytes to ConA and TT in each treatment group (n = 35)
      was not different at baseline or postsupplementation. Children supplemented with
      zinc + vitamin A tended to show higher proliferative responsiveness of T
      lymphocytes to PPD than did those treated with placebo (P = 0.08). This tendency
      was observed in females but not in males. Increased zinc and vitamin A intake
      could result in health benefits for children living in regions endemic for
      suboptimal micronutrient nutriture.

PMID- 8147962
TI  - Epidemiology and transmission of HIV-2. Why there is no HIV-2 pandemic.
AB  - Although human immunodeficiency virus type 1 (HIV-1) and HIV-2 share modes of
      transmission, their epidemiologic characteristics differ and international spread
      of HIV-2 has been very limited. Recently, the prevalence of infection with HIV-1
      but not HIV-2 has increased rapidly in different West African countries, where
      HIV-2 was probably present earlier. Among 19,701 women of reproductive age tested
      in Abidjan, Ivory Coast, between 1988 and 1992, the prevalence of HIV-1 infection
      increased from 5.0% to 9.2%, while that of HIV-2 declined from 2.6% to 1.5%.
      Differences in viral load may be responsible: reported results of virus culture
      and polymerase chain reaction assays suggest that at high CD4+ T-lymphocyte
      counts viral load is lower in HIV-2-infected than in HIV-1-infected persons; the
      efficacy of heterosexual and perinatal transmission of HIV-2 is less efficient
      than that of HIV-1 at this stage. At low (< 0.20 x 10(9)/L [< 200/microL]) CD4+ T
      lymphocyte counts, virus isolation is equally successful for both viruses, and
      the efficacy of heterosexual transmission is similar. Differences in HIV-1 and
      HIV-2 natural history are reflected in differences in viral load, that for HIV-2
      being lower until immunodeficiency is severe. Differences in viral load
      throughout most of the natural history of infection appear to correlate with
      lower transmissibility of HIV-2 than HIV-1, and are the likeliest explanation for
      their markedly different global epidemiology.

PMID- 8147963
TI  - A comparison of two systems for assessing cerebral venous oxyhaemoglobin
      saturation during cardiopulmonary bypass in humans.
AB  - The Somanetics Invos 3,100 cerebral oximeter is a new noninvasive device which
      measures the regional oxygen saturation of haemoglobin within the cerebral
      microvasculature by infrared spectroscopy. It was used in nine patients
      undergoing elective cardiac surgery and its results were compared with
      measurements of jugular venous bulb saturations obtained by the Oximetrix
      Opticath oximetry system. The index value of jugular venous bulb saturation was
      obtained by analysis of jugular bulb blood in an Il282 cooximeter. The cerebral
      oximeter was less accurate and precise (standard deviation of difference 14.1%)
      than the Oximetrix system (standard deviation of the difference 2.65%) and also
      demonstrated a systematic error in bias unrelated to cerebral perfusion pressure.
      The cerebral oximeter may therefore be less useful than jugular venous bulb
      saturation in the clinical management of patients undergoing cardiopulmonary
      bypass.

PMID- 8147964
TI  - Behavior, cortical ectopias, and autoimmunity in BXSB-Yaa and BXSB-Yaa+ mice.
AB  - The BXSB-Yaa recombinant inbred strain was created by crossing a male SB/Le with
      a female C57BL/6J. A Y chromosome factor derived from the SB/Le male, known as
      the autoimmune accelerator (Yaa), leads to an earlier onset and greater severity
      of autoimmune disease in males. In contrast, male BXSB mice, which lack the Yaa
      gene (called BXSB-Yaa+) because their Y chromosome is derived from the C57BL/6J,
      do not develop an autoimmune condition. To examine the influence of the Y
      chromosome on behavior, cortical ectopia incidence, and immune functioning, males
      and females of these two strains were compared. Significant strain differences
      (for both sexes) were found for behavioral measures including discrimination,
      spatial and avoidance learning, and activity. For immunological parameters, a sex
      difference was seen in the BXSB-Yaa (males more autoimmune), but not in the BXSB
      Yaa+ strain. As expected, male BXSB-Yaas were more autoimmune than male BXSB
      Yaa+s. However, there was also a strain difference for IgG in the females (BXSB
      Yaa+ greater). No strain difference was found for the presence of ectopias.
      However, there was a sex difference across both strains, with males having a
      higher incidence. BXSB-Yaa and BXSB-Yaa+ mice have behavioral and immunological
      differences greater than would be predicted by their known genetic differences.
      The significant differences between the two female groups suggest that the two
      strains differ with respect to autosomal genes, in addition to the Y chromosome.
      The incidence of ectopias is independent of this genetic difference and is
      influenced by the subject's sex.

PMID- 8147965
TI  - Increased SIL-2R levels in celiac disease.

PMID- 8147966
TI  - Natural family planning. Depends on consumers not providers.

PMID- 8147967
TI  - Near infrared spectroscopy.

PMID- 8147968
TI  - Management of acute symptomatic hyponatremia.

PMID- 8147969
TI  - ATP sensitive potassium channels and ischemic heart disease.

PMID- 8147970
TI  - Roles of glycogen synthase kinase-3 in signal transduction.

PMID- 8147971
TI  - The definition of alcoholism.
AB  - Formulations of alcohol dependence are continuously refreshed, in line with
      changing concepts and altered needs. Two new descriptions have been prepared: the
      revised WHO criteria for substance use disorders and an educative definition of
      alcoholism. The major sets of diagnostic criteria provided by WHO and by the
      American Psychiatric Association are moving closer together but have not solved
      all the semantic problems. More refined assessments are also available to quicken
      fulfillment of the long-awaited hope that treatments can be matched to patients.

PMID- 8147972
TI  - Alcohol-associated generation of oxygen free radicals and tumor promotion.
AB  - We discuss evidence indicating how ethanol could generate oxygen free radicals.
      Recent use of techniques such as spin trapping and EPR spectroscopy have
      demonstrably confirmed that both acute and chronic alcohol use by laboratory
      animals would generate free radical intermediates. These radicals are of
      biological origin and presumably involve lipids. However, an exact identification
      of the intermediates produced has not been worked out with the currently
      available methodologies. Also not known is the mechanism whereby ethanol could
      initiate free radicals. The relationship between generation of free radicals and
      cell toxicity or carcinogenesis is also not understood. Using a variety of
      systems that included different species, strains and gender (male Sprague-Dawley
      and Fisher-344 rats, female C57BL/6 mice, male Syrian golden hamsters) and
      carcinogens (NMBZA, NNN, NNK, DMBA and LP-BM5 retrovirus) we have shown an
      association of lipid peroxidation with ethanol tumor promotionability. However,
      the process of tumor promotion in general is not very clear and the role played
      by ethanol in this process is still more unclear. Here we are reviewing evidence
      that could possibly be involved in such promotion processes.

PMID- 8147974
TI  - Maternal ethanol consumption induces transient compensatory hyperplasia of
      developing cardiac tissue in the neonatal rat.
AB  - The effect of continuous exposure to ethanol in utero and postpartum on growth
      and cell division in developing cardiac tissue was studied in neonatal Fischer
      rats. Pregnant and lactating females were maintained on three dietary regimens; a
      control group fed rat chow ad libitum, an experimental group receiving an ethanol
      containing (6% by volume) liquid diet, and a pair-fed control group, which
      received an isocaloric amount of control liquid diet. At days 1, 5, and 10
      postpartum, five litters of pups from each control and experimental group were
      sacrificed and the body weights, heart weights, heart-to-body weight ratios, and
      mitotic frequency of the ventricular myocardium were measured. When compared to
      either group of controls, pups continuously exposed to dietary ethanol expressed
      significantly (P < 0.01) lower body weights. Pups maintained by the pair-fed
      females had significantly (P < 0.01) lower body weights at days 5 and 10 than
      pups maintained by the chow-fed females, indicating a pair-fed effect of
      suboptimal nutrition of the model. As the pups developed, the heart weights of
      pups maintained by the chow-fed females became progressively greater (P < 0.01)
      than the heart weights of pups maintained by the pair-fed and ethanol-fed
      females, which expressed no weight difference. The reduction of heart weight
      present in the ethanol-fed and pair-fed pups represents a pair-fed effect of
      suboptimal nutrition and not an obvious effect of exposure to dietary ethanol.
      The ratio of heart weight to body weight and mitotic frequency were significantly
      greater (P < 0.01) in 1- to 5-day-old pups exposed to ethanol. Following day 5,
      these parameters decreased and approached the control values. This indicates that
      growth of cardiac tissue is not suppressed in the 1- to 5-day-old rat pups
      exposed continuously to dietary ethanol. These observations further suggest the
      presence of a mechanism intrinsic to the heart which can provide stage-dependent
      protection from the adverse effects of ethanol during early development. The
      decline in heart weight to body weight ratios and mitotic frequency in pups of
      ethanol-fed females also suggests that ethanol may initiate suppression of the
      growth of cardiac tissue or may incur stage-dependent injury during the later
      stages of development. The possible mechanism of this stage-dependent protection
      during early neonatal development is an increased mitotic activity of the cardiac
      myocytes.

PMID- 8147973
TI  - Effects of calcium antagonists on central actions of ethanol: comparative studies
      with nifedipine, verapamil and cinnarizine.
AB  - The effects of nifedipine (17.5 and 50 mg/kg), verapamil (5 and 15 mg/kg) and
      cinnarizine (75 and 200 mg/kg) on acute toxicity and central actions of ethanol
      (i.e. ethanol-induced sleep and hypothermia, disturbances of rota-rod performance
      and spontaneous activity) were investigated in mice. Additionally, effects of
      these drugs on the development of tolerance to hypothermic and sleep-inducing
      action of ethanol were studied in rats. Calcium antagonists were given acutely 30
      min before ethanol administration, or chronically once daily (lower dose) for 10
      days, and on the 11th day the animals received an ethanol injection. Single doses
      of nifedipine increased the acute toxicity of ethanol and potentiated its central
      effects. After long-term administration of nifedipine no significant alterations
      in the central actions of ethanol were observed. Verapamil and cinnarizine
      antagonized the ethanol-induced sleep and impairment of locomotor activity.
      Nifedipine did not affect the development of tolerance to hypnotic and
      hypothermic action of ethanol. Verapamil prevents the development of tolerance to
      hypnotic action of ethanol, whereas cinnarizine prevents the development of
      tolerance to the hypnotic and hypothermic action of ethanol.

PMID- 8147975
TI  - Ethanol-induced alterations in gonadotrophins secretion during the estrous cycle
      of rats.
AB  - The effects of ethanol administration during a preovulatory period on both serum
      and pituitary gonadotrophin concentrations were studied in female rats. The
      animals were injected with 2 g/kg of ethanol (30% v/v, in saline solution) at
      18:00 hr of diestrous 2. Hormonal levels were measured by RIA at different times
      during the estrous cycle, especially during the proestrus day. The preovulatory
      LH surge was inhibited using ethanol. Serum LH levels decreased between 16.00 and
      20.00 hr of proestrus (P < 0.01). The levels of FSH in serum were slightly
      depressed by ethanol between 12.00 and 17.00 hr of proestrus (P < 0.05 with
      respect to the control set), but the values during the proestrus surge (18.00
      20.00 hr) were unaffected. Ethanol augmented pituitary hormonal content during
      the periods in which serum hormonal levels decreased (P < 0.05 with respect to
      the control set) but it did not affect gonadotrophins synthesis. The increase in
      pituitary gonadotrophin concentrations induced by ethanol during the proestrus
      day is due to the accumulation of the hormone which was not released before. The
      preovulatory LH surge was re-established in the next cycle (5th day after
      treatment). These effects of ethanol on gonadotrophin levels could explain the
      previously observed anovulatory effects induced by ethanol administration in
      diestrous.

PMID- 8147976
TI  - Effects of seed saponins of Thea sinensis L. (Ryokucha saponin) on alcohol
      absorption and metabolism.
AB  - We evaluated the effects of the seed saponins of Thea sinensis L. on alcohol
      absorption and metabolism in rats and mice. An ethanolic extract from the seeds
      of T. sinensis was orally administered to the rats 1 hr before or 0.5 hr after
      administration of ethanol (2 g/kg), and the blood ethanol assayed 0.5, 1, 2, 3,
      and 4 hr after ethanol administration. The ethanol level decreased after both pre
      and post-administration of the extract. The extract was further purified to
      obtain a saponin fraction which was orally administered to mice 1 hr before
      ethanol administration. Blood, liver, and stomach were obtained 0, 1, 3, and 6 hr
      after ethanol administration, and the ethanol, acetaldehyde, acetate, and acetone
      concentrations in each specimen were measured by head space gas chromatography.
      The saponin fraction decreased the ethanol levels in the blood and liver but
      increased that in the stomach five-fold over the control level, suggesting
      inhibition of alcohol absorption. The ethanol disappearance time from the blood
      was shortened, suggesting the promotion of alcohol disappearance. The acetate and
      acetone levels were unaffected. However, the acetaldehyde level decreased in the
      blood, liver, and stomach. The decreases in the ethanol and acetaldehyde levels
      in the liver suggested the protective effects of the seed saponins on the liver.
      The saponins did not directly inhibit hepatic alcohol dehydrogenase activity. The
      seed saponins of T. sinensis seem to suppress alcohol absorption by slowing
      gastric emptying and by inhibiting absorption across the cell membranes of the
      digestive tract.

PMID- 8147977
TI  - Plasma xanthine oxidase level and alcohol administration.
AB  - The acute administration of ethanol by gastric catheter significantly increases
      the plasma xanthine oxidase activity in both rats and hamsters without changing
      other enzyme activities--alanine aminotransferase and aspartate aminotransferase.
      The plasma xanthine oxidase level seems to be a sensitive marker of liver damage.
      Its higher activity due to the acute ethanol intoxication may have an impact on
      ethanol organ damage.

PMID- 8147978
TI  - Familial alcoholism and ERPs: differences in probability sensitivity?
AB  - Event-related potentials (ERPs) were recorded from sons (age 11-14) of families
      that were positive (FH+) and negative (FH-) for alcoholism in response to
      circles, triangles and squares presented in four colors with a single central
      digit. A button was pressed for successive presentations of identical stimuli
      (target probability = 0.2). Reduced late positivity in FH+ boys has been
      previously reported. This positivity was shown to increase with the number of
      features that match target requirements. FH- boys responded more quickly, but no
      less accurately, than FH- boys, and were characterized by reduced ERP stimulus
      selectivity. That is, FH+ boys not only produced less P3 than FH- boys in
      response to targets, but generally produced more late positivity than FH- boys in
      response to nontargets. The pattern of group differences was most consistent with
      FH+ boys exhibiting both reduced ERP effects of target features in general, and a
      specific insensitivity to matching digits. It is hypothesized that these effects
      result from reduced sensitivity to information about the frequency with which
      categories of events occur, and that this may be characteristic of those at high
      risk for alcoholism.

PMID- 8147979
TI  - Hip fractures in middle-aged men: a consequence of early retirement and alcohol
      misuse?
AB  - From the 1950s to the 1980s the incidence of hip fractures in women aged 50-64
      and cervical fractures in men of the same age in Malmo did not increase, whereas
      the incidence of trochanteric fracture in men aged 50-64 increased significantly.
      Significant background factors in men were alcohol misuse, living alone, early
      retirement, previous fractures, low weight/height ratio and less severe trauma-
      more in men with trochanteric than in men with cervical fracture. The deviant
      life-style and suspected physical inertia in this group of middle-aged men
      probably predisposes to osteoporosis and increased fracture risk.

PMID- 8147980
TI  - Consumption and harm: drinking patterns of the Irish, the English and the Irish
      in England.
AB  - There has been controversy over the relationship between alcohol consumption and
      related problems amongst the Irish in England. Irish migrants have high
      Standardised Mortality Ratios for chronic liver disease and cirrhosis and high
      hospital admission rates for alcohol-related diagnoses in England. Yet it has
      been considered that people from the Republic of Ireland, whether living in
      Ireland (Conniffe et al., 1990) or in England (Pearson et al., 1991), actually
      drink less than the English. This paper reviews the evidence. In recent years
      Irish per capita volume alcohol consumption has been comparable to that of the
      U.K., although the distribution of consumption differs. Women in Ireland are less
      likely to drink than women in England and Wales, while men in Ireland are more
      likely to drink at high-risk levels than men in England and Wales: their average
      weekly consumption levels are closer to those of high-consuming men in Yorkshire
      and Humberside, who also drink more than the U.K. national average. Men in
      Ireland also appear to be more likely to experience drinking problems than their
      counterparts in England and Wales, although this may be related to factors other
      than the total amount of alcohol consumed. Although a previous study of General
      Household Survey data indicated low-risk alcohol consumption levels for people
      from the Irish Republic living in Britain, a reanalysis of these data adjusting
      for age and gender shows drinking rates that are very high.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8147981
TI  - Emergency oxygen: What? Who? When?
AB  - 1. While the need for oxygen to support ill or injured clients is well
      established, confusion exists about oxygen devices and legal and training
      requirements. 2. The FDA recognizes both emergency and prescription oxygen.
      Emergency devices may be used legally by a non-health care workplace first aider
      who has completed a course in oxygen administration. Training sources for oxygen
      administration training are identified. 3. Workplace first aiders may assist a
      client and occupational health nurse by administering emergency oxygen. The
      appropriate use of these devices for cases of cardiac distress/arrest, shock,
      COPD, and hyperventilation is reviewed.

PMID- 8147982
TI  - Preventive measures applied by RNs in occupational health settings: a descriptive
      study.
AB  - 1. Registered nurses employed in hospital settings spent more time with primary
      prevention measures than did nurses employed in textile settings. 2. Nurses
      employed less than 3 years spent more time with primary prevention activities
      than did nurses employed more than 15 years. 3. The education of nurses in the
      last decade includes an increasing emphasis on wellness models. 4. A commitment
      to education, research, and practice will facilitate measures that focus on
      primary prevention.

PMID- 8147983
TI  - Gender differences in research.

PMID- 8147984
TI  - Management of traumatic injuries in the workplace.
AB  - Traumatic injuries in the workplace occur from a variety of mechanisms and may
      produce a wide range of injuries. Critical to the management of these injuries is
      the knowledge that life saving interventions for airway, breathing, and
      circulation must take priority. Controlling external bleeding and managing
      circulation is imperative in the traumatically injured worker. Inadequate control
      of hemorrhage leads to cellular shock from which the client may never recover.
      Extremities should be managed appropriate to the specific injury. Careful
      monitoring of neurovascular status is significant in limb preservation. Amputated
      parts must be meticulously cared for, with the vision of replantation in mind.
      Electrical burns are unique burn injuries, as the complete area of damage is not
      visible. Monitoring cardiac and respiratory function is essential to detect any
      life threatening abnormalities in all injuries, but is especially important in
      the electrically injured client. The occupational health nurse can make a
      significant difference in the outcome of a traumatically injured client in the
      workplace. Adequate knowledge of treatment modalities, as well as transfer to the
      most appropriate trauma care facility, can make the difference in obtaining the
      best possible outcome.

PMID- 8147985
TI  - Preventing homicide in the workplace.

PMID- 8147986
TI  - The Americans with Disabilities Act: importance to occupational health.

PMID- 8147987
TI  - A heart health survey at the worksite: the first step to effective programming.
AB  - 1. Cardiovascular disease is the number one killer in Canada, accounting for 42%
      of all deaths. 2. Workplace policy and health promotion programs can have a
      significant impact on modifiable risk factors associated with the development of
      heart disease. 3. This article describes the results of a worksite cardiovascular
      risk behavior screening of 652 mining employees in Sudbury, Ontario. 4. The
      theoretical framework for this study is based on the PRECEDE-PROCEED model: to
      reach the ultimate outcome, improved quality of life changes must be made at both
      the individual as well as the environmental (workplace) level (Green, 1991).

PMID- 8147988
TI  - Hospital based occupational health services: meeting community needs.
AB  - 1. Community health plans must include comprehensive approaches to meeting
      employment related health care needs. 2. To be effective, occupational health
      services should be based on a complete assessment of the needs of employers in
      the community. 3. Integration of community health care resources requires strong
      communication links, cooperation, and collaboration among providers.

PMID- 8147989
TI  - The revised NIOSH lifting guidelines. Application in a hospital setting.
AB  - 1. Ergonomic interventions, which include the application of biomechanical
      models, are an integral part of a workplace injury control program. 2. The NIOSH
      1991 Lifting Guide is an example of a biomechanical model. It is utilized as an
      assessment tool in the ergonomic analysis of a task performed by hospital nursing
      personnel. 3. The risk for musculoskeletal injury is quantified from the
      analysis. Economically feasible modifications to the task are outlined to reduce
      the associated lifting hazards.

PMID- 8147990
TI  - Chemical abuse rehabilitation for hospital employees: examination of benefit
      usage when referred by an employee assistance professional.
AB  - 1. Chemical abuse is the third leading health problem in the United States.
      Approximately 7 million workers are addicted to chemicals. 2. There is a
      relationship between chemical abuse and poor job performance (decreased
      productivity and efficiency, tardiness) and excessive use of sick time,
      disability, and workers' compensation. 3. An equivalent quasi-experimental design
      with a control group was used to examine benefit usage pre- and post-chemical
      abuse rehabilitation. Wilcoxon's signed rank test demonstrated sick time, late
      arrival/early departure, and absent time were not comparable before
      rehabilitation, but became similar after rehabilitation. 4. The researcher
      concluded that chemically dependent hospital employees who are referred and
      complete an inpatient rehabilitation program will experience benefit usage
      comparable to the employee population without recognized chemical abuse.

PMID- 8147991
TI  - Occupational health software: selecting the right program.
AB  - 1. Occupational health nurses who are selecting software should identify specific
      goals for computerization, such as tracking compliance activities or analyzing
      trends. 2. Nurses should evaluate software programs by the extent to which each
      achieves these goals without exceeding available resources. 3. Successful
      software installations require commitment from an on site project manager to
      ensure that the program meets specifications and that the vendor provides
      adequate user training and ongoing support.

PMID- 8147992
TI  - Providing health promotion to a dispersed population.
AB  - Health promotion in the 1990s and beyond needs to be flexible, designed for
      specific populations based on needs assessment, and available to participants at
      the time of need. The program also must be continuously evaluated and updated as
      the needs of the participants and corporation change.

PMID- 8147993
TI  - Health care reform: antitrust and competitive implications for nursing.

PMID- 8147994
TI  - Cholesterol management: guidelines have changed, although diet is still central.
AB  - 1. The second report of the National Cholesterol Education Program's Adult
      Treatment Panel re-emphasizes low density lipoprotein cholesterol as the main
      target of cholesterol lowering therapy; dietary therapy as the first line
      approach to cholesterol management; and the reservation of drug therapy for
      clients at high risk for coronary heart disease (CHD). 2. In the new treatment
      guidelines, the type and intensity of cholesterol treatment, which now involves a
      greater emphasis on the high density lipoprotein cholesterol level, is guided by
      the client's CHD risk status. 3. Under the new recommendations, dietary
      management of high blood cholesterol, which is the cornerstone of cholesterol
      intervention, should also include greater attention to increasing the client's
      physical activity and losing weight if needed. 4. The new cholesterol
      intervention guidelines not only provide occupational health nurses with new
      directions for cholesterol intervention, but reinforce the critical role of
      nurses in providing a more holistic, integrated approach to risk factor
      reduction.

PMID- 8147995
TI  - Managing drug therapy: new insights into the National Cholesterol Education
      Program guidelines.
AB  - 1. The National Cholesterol Education Program ATP II Report clearly defines those
      individuals most likely to benefit from drug therapy for treatment of
      cholesterol. 2. Knowing the choice of drugs, method of action, administration
      hints, and side effects of these agents is important for occupational health
      nurses. 3. The nurse's role in providing education, defining techniques to
      enhance compliance to medications, and reinforcing change in lifestyle behaviors
      is key to the client's success in maintaining life long therapy for cholesterol
      management.

PMID- 8147996
TI  - Cholesterol intervention in the workplace: successful integration with other risk
      reduction programs.
AB  - 1. Despite substantial progress in reducing cardiovascular disease in the United
      States, 52 million Americans with elevated cholesterol still require dietary
      intervention and another 12.7 million may require drug intervention. 2. Only one
      third of the population who need lipid management receive it; 40% of people who
      have seen a physician in the past 2 years have never been screened for
      cholesterol. Therefore, screening at the worksite may provide an opportunity for
      cholesterol awareness and follow up evaluation. 3. It is important to understand
      the different behavioral models which help motivate individuals to make lifestyle
      changes. Generally, a combination of these models can be used successfully at the
      worksite in promoting health behavior changes. 4. Because the employer benefits
      from health promotion programs, it should be an integral part of the occupational
      health nurse's role. The most successful programs offer information about making
      lifestyle changes and provide individual and group support.

PMID- 8147997
TI  - Lowering cholesterol levels in children and adolescents: a role for the
      occupational health nurse.
AB  - 1. The atherosclerotic process begins in childhood and is influenced by genetics,
      diet, and lifestyle. Abnormal cholesterol levels are not uncommon in children. 2.
      The NIH Expert Panel on Blood Cholesterol Levels in Children and Adolescents
      recommends heart healthy eating for all children over the age of 2 years. This
      eating pattern is nutritionally adequate and lowers amounts of saturated fatty
      acids and total fat in the diet. 3. Children with a family history of premature
      coronary heart disease or elevated cholesterol levels should have a lipoprotein
      analysis to assess for abnormal levels. 4. The occupational health nurse has an
      important role in assisting families in which parents and children have lipid
      disorders.

PMID- 8147998
TI  - A nursing approach to elevated cholesterol and triglycerides: case studies.

PMID- 8147999
TI  - Postexposure requirements and counseling issues resulting from the bloodborne
      pathogens standard.
AB  - The management of employees during follow up for an occupational exposure for
      bloodborne pathogens presents clear opportunities and challenges for the
      occupational health nurse. These include understanding the intent of the OSHA
      Bloodborne Pathogens Standard, identifying postexposure follow up requirements,
      counseling workers for pre- and posttest procedures, protecting the
      confidentiality of medical records and information, and educating both employees
      and management about bloodborne pathogens and the potential for transmission.
      Postexposure follow up is also another opportunity for the occupational health
      nurse to educate employees about health promotion and disease prevention.

PMID- 8148000
TI  - HIV educational interventions with low risk groups.

PMID- 8148001
TI  - Professional presentations: transmitting information with polish and flair, Part
      I--Preparing the presentation.
AB  - Writing a presentation requires the speaker to know the audience and the purpose
      of the presentation. Research, whether in the library or through interviews, is
      important for a presentation to be current and accurate. The organization of the
      presentation hinges on a clear central idea, measurable objectives, coherent
      outline complete with main points and supporting material, effective transitions,
      an introduction that previews the presentation, and a conclusion that summarizes
      it. This process provides a foundation for a presentation that is interesting,
      informative, and memorable.

PMID- 8148002
TI  - Two inhibitors of platelet aggregation from a Panus species (Basidiomycetes).
AB  - Two inhibitors of platelet aggregation were isolated from fermentations of Panus
      sp. 9096. One inhibitor proved to be identical to naematolon (2), an antibiotic
      previously isolated by S. Backens et al. from several Hypholoma species. The
      other metabolite, panudial (1), is a new nordrimane (cis-annelation of the
      bicyclus) lacking the carbon atom in position 10 of the drimane skeleton.
      Panudial is a potent inhibitor of bovine and human platelet aggregation
      stimulated by different inducers.

PMID- 8148003
TI  - Uncoupling by trehalose of Ca2+ transport and ATP hydrolysis by the plasma
      membrane (Ca2+ + Mg2+) ATPase of kidney tubules.
AB  - Trehalose, the disaccharide of glucose, inhibits both initial rate and maximal
      capacity of ATP-dependent Ca2+ transport in inside-out vesicles of basolateral
      membrane from kidney proximal tubules. This inhibition (I0.5 = 60 mM) cannot be
      attributed to an increase in Ca2+ permeability, since the rate of EGTA-stimulated
      Ca2+ efflux from preloaded vesicles is not modified by trehalose. In the presence
      of 600 mM trehalose, Ca2+ uptake was almost completely inhibited, but the Ca(2+)
      stimulated ATPase activity was unaffected; thus trehalose uncouples the Ca2+
      transport from the ATPase activity. The Ca2+ transport inhibition by trehalose is
      reversible, since the inhibition disappeared when the vesicles were pre-incubated
      with 600 mM trehalose and then diluted in reaction medium to measure Ca2+
      accumulation. Other mono- and disaccharides such as glucose, fructose, galactose,
      sucrose, maltose and lactose were tested but were not so effective as trehalose.
      The uncoupling of Ca2+ transport from hydrolysis can be explained by an
      interaction of trehalose with the phospholipid environment of the enzyme that
      induces conformational changes in specific domains of the enzyme so as to impair
      the coupling process.

PMID- 8148004
TI  - 31P NMR studies on perfused liver from mouse with chronic ethanol ingestion.
AB  - Changes in the levels of phosphate metabolites as affected by acute ethanol
      administration and chronic ethanol ingestion were investigated in perfused mouse
      liver by 31P NMR spectroscopy. Acute ethanol administration decreases
      intracellular Pi and the Pi/ATP ratio, and increases phosphomonoester levels in
      normal-fed animals. No such change was observed in the liver from ethanol-fed
      mice. Chronic ethanol ingestion renders the liver more prone to ischemia-induced
      changes in ATP, intracellular Pi and phosphomonoesters. The Pi/ATP ratio
      increases fivefold in control mice and fourfold in alcohol-fed mice when ischemia
      is induced in the presence of ethanol. Intracellular pH of 7.45 +/- 0.05 is not
      affected by ethanol perfusion. Cellular acidosis resulting from ischemia in the
      presence or absence of alcohol was similar. However, longer period of ischemia
      leads to an additional 0.11 unit drop in pH in the presence of ethanol.

PMID- 8148005
TI  - Xanthanolides of Xanthium italicum Moretti and their biological activity.
AB  - Seven xanthanolides were identified in the extract of X. italicum leaves.
      Antibacterial and cytotoxic activities were found for the total extract and its
      major constituents xanthinin and xanthatin.

PMID- 8148006
TI  - Purification and properties of acridone synthase from cell suspension cultures of
      Ruta graveolens L.
AB  - Acridone synthase has been purified from cell suspension cultures of Ruta
      graveolens using a combination of gel filtration and ion exchange chromatography.
      The purified enzyme has an apparent molecular weight of 69 kDa on gel filtration
      and a subunit structure on SDS-PAGE of 40 kDa. The apparent Km-values are 10.64
      microM and 32.8 microM for N-methylanthraniloyl-CoA and malonyl-CoA,
      respectively. Tryptic digestion of the homogeneous acridone synthase was
      performed. Seven of the peptides were chosen for microsequencing. The homology of
      the amino acid sequences from this particular polypeptide and corresponding
      peptides from chalcone synthase 3 from garden pea amounted to 76%.

PMID- 8148007
TI  - Evidence for nickel in the soluble hydrogenase from the unicellular green alga
      Scenedesmus obliquus.
AB  - Cultures of the green alga Scenedesmus obliquus were grown in the presence of
      either the chelating reagent EDTA or NiCl2 in various concentrations and assayed
      for hydrogenase catalyzed photohydrogen evolution after an anaerobic dark
      adaptation period. Cultivation of algae in the presence of 100 microM EDTA
      inhibited the formation of hydrogenase activity by 37%. After a cultivation of
      the cells in the presence of 5-20 microM NiCl2 photohydrogen evolution was
      increased by 20-40%. Addition of EDTA up to a final concentration of 1.5 mM had
      no effect on the activity of hydrogenase in cell-free hydrogenase preparations.
      Cultures grown in the presence of radioactive 63NiCl2 incorporated 63Ni in a
      parallel fashion to the cell growth. In radioactive labeled hydrogenase
      preparations a co-elution of radioactivity and hydrogenase activity could be
      observed using gel filtration chromatography.

PMID- 8148008
TI  - Biochemical activities of propolis-extracts. III. Inhibition of dihydrofolate
      reductase.
AB  - Ethanolic and aqueous extracts of the natural compound PROPOLIS indicate
      substantial antiinflammatory functions as well as antibiotic activities in vitro
      and in vivo. The exact mode of physiological or biochemical mechanisms
      responsible for the medical effects, however, is all but clear. The
      standardization on the basis of quantitative determination of prominent
      components of these extracts have been substituted recently by simple biochemical
      model reactions including photodynamic properties. In this communication we
      report on the inhibitory activity of an aqueous extract of propolis on the enzyme
      dihydrofolate reductase. This activity may at least partially be due to the
      content of caffeic acid, as revealed by HPLC chromatography and comparative
      activity tests of representative ingredients of the propolis extract. This result
      may explain some of the protective functions of propolis, similar to those shown
      for several "non-steroidal antiinflammatory drugs", NSAIDs.

PMID- 8148009
TI  - Insecticidal and fungicidal compounds from Isatis tinctoria.
AB  - Tryptanthrin (1), indole-3-acetonitrile (2) and p-coumaric acid methylester (3)
      were isolated from the aerial parts of Isatis tinctoria L. The compounds show
      insecticidal and anti-feedant activity against termites (Reticulitermis
      santonensis), insect preventive and control activity against larvae of the house
      longhorn beetle (Hylotrupes bajulus) and fungicidal activity against the brown
      rot fungus (Coniophora puteana).

PMID- 8148010
TI  - Purification, characterization and N-terminal sequence of phosphoserine
      aminotransferase from the green alga Scenedesmus obliquus, mutant C-2 A'.
AB  - Phosphoserine aminotransferase (EC 2.6.1.52), an enzyme of the "phosphorylated
      pathway" leading to the formation of serine, was purified from Scenedesmus
      obliquus, mutant C-2 A'. Purification started from the soluble supernatant of a
      crude cell homogenate and included different affinity and DEAE chromatographic
      techniques, as well as gel filtration. The purified phosphoserine
      aminotransferase was enriched 1537-fold and identified to be a homodimer with
      subunit molecular masses of 40 kDa, each. The absorption spectrum is consistent
      with the presence of pyridoxal-5-phosphate as cofactor. From the purified enzyme
      18 amino acids of the N-terminus could be determined, showing at least 67%
      homology with the serC gene encoding phosphoserine aminotransferases from
      bacterial organisms.

PMID- 8148011
TI  - Proteolysis in heterocyst-forming cyanobacteria: characterization of a further
      enzyme with trypsin-like specificity, and of a prolyl endopeptidase from Anabaena
      variabilis.
AB  - Soluble extracts of the cyanobacterium Anabaena variabilis ATCC 29413 and an
      engineered mutant that lacks an intracellular protease cleaving after Lys and Arg
      (Maldener, Lockau, Cai, and Wolk, Mol. Gen, Genet. 225, 113-120 (1991)) were
      separated by ion exchange chromatography, and protease profiles determined using
      azocasein, N alpha-benzoyl-D,L-arginine-4-nitroanilide and N-carbobenzoxy-glycyl
      L-proline-4-nitroanilide as substrates. A second enzyme cleaving at the carboxyl
      side of lysine and arginine, and a prolyl endopeptidase were detected, enriched
      and characterized. Both proteolytic enzymes appear to be located in the
      periplasm.

PMID- 8148012
TI  - Evidence for nucleosomal phasing and a novel protein specifically binding to
      cucumber satellite DNA.
AB  - The nucleosomal organization and the protein-binding capability of highly
      repeated and methylated satellite DNA of cucumber (Cucumis sativus L.),
      comprising approx. 30% of the genome, were analyzed. Nucleosomal core DNA from
      satellite type I was prepared after micrococcal nuclease digestion of chromatin
      and sequenced. Most of the core sequences obtained could be grouped in two main
      (A and B) and two minor groups (C and D) indicating a specific and complex
      phasing of nucleosomes on this satellite DNA. In vitro, gel retardation assays
      with cloned satellite DNA repeats (types I-IV) demonstrated a specific binding of
      nuclear proteins. These specific binding effects are also obtained with genomic,
      in vivo methylated and sequence heterogeneous (1 to 10% diversity) satellite type
      I DNA. For the first time in plants, a satellite DNA-binding protein with an
      apparent molecular weight of 14 kDa (SAT 14) was identified.

PMID- 8148013
TI  - [The present possibilities for routine use of blood-saving measures from the
      anesthesiologic point of view--theoretical basis and clinical practice. II:
      Perioperative retransfusion of acute blood loss; plasmapheresis].
AB  - Intra- and postoperative blood-salvage with consecutive retransfusion represent
      an established part within the "Concept of Autologous Transfusion (CAT)".
      According to the processing technique of the blood salvaged there exist two
      different systems: Autologous Transfusion System II (ATS II) and Autologous
      Transfusion System III (ATS III). By using ATS II blood (with or without
      anticoagulation) is collected within a collecting reservoir after having passed a
      rough-filter-system. Passing a fine-filter-system the blood collected is
      retransfused into the patient without any preceding processing (autologous direct
      retransfusion, ADR). Because of the activation of the coagulation proteins by the
      tissue and by the collection system as well as due to the destroyed red blood
      cells, the white blood cells, the platelets and the free plasma hemoglobin the
      patient is transfused with an autologous "whole-blood-like product" of minor
      quality. By administration of ATS III blood is collected and anticoagulated and
      passes a rough-filter as well; by processing the blood by means of centrifugation
      and separation and by washing the damaged red blood cells, a great part of the
      white blood cells, of the platelets and of the plasma hemoglobin (and of the
      anticoagulatory drug) is eliminated resulting in a washed autologous product,
      which mainly consists of red blood cells, which are retransfused into the patient
      through a fine-filter system. This means, that the autologous product obtained by
      the two different systems differs both regarding its quality and the plasmatic
      and corpuscular contents. However, undoubtedly either system is able to
      effectively reduce the need for homologous blood.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8148014
TI  - [The present possibilities for routine use of blood-saving measures from the
      anesthesiologic point of view--theoretical bases and clinical practice. III.
      Autologous blood donation, autologous donation criteria and organizational
      measures].
AB  - This third part of a review on "Autologous Transfusion" deals with preoperative
      autologous blood donation, with supplemental pharmaco-therapy, with election
      criteria of the patient as well as with the organizational measures to be taken
      into account if an intensive autologous predeposit programme is routinely
      applied. Donation of an autologous predeposit aims at supplying the patient with
      autologous blood and autologous plasma, respectively, according to the expected
      blood loss and in order to reduce the need for homologous transfusion. Important
      aspects, which have to be considered if applying a routine autologous donation
      programme refer both to the election criteria of the patient and to the
      organizational programme and measures to be considered. Data in the literature
      reveal, that the risk of side effects for the patient (who is both the donor and
      the receiver of the (autologous) blood) during and after donation of an
      autologous predeposit is definitely not greater than the risk reported for
      otherwise healthy homologous volunteers. In our opinion, this means, that a
      patient who has been declared eligible for an elective operative intervention
      which makes homologous transfusion very probable, can be considered eligible for
      donating an autologous predeposit; additionally, he should also be eligible for
      acute normovolemic hemodilution, as donating an autologous predeposit with
      accompanying volume substitution of the predeposit 'is under hemodynamic aspects'
      nothing else than an acute and preoperatively performed normovolemic
      hemodilution. Analysing the data so far reported, volume substitution of the
      autologous predeposit appears to be a very important component for the patient's
      safety.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148015
TI  - [The present possibilities for routine use of blood-saving measures from the
      anesthesiologic point of view--theoretical bases and clinical practice. IV:
      Supportive administration of erythropoietin and iron].
AB  - In clinical studies erythropoietin has been shown to effectively increase the
      autologous predeposit in patients undergoing elective surgery; however, the
      results demonstrating a reduction of homologous transfusion are not equally
      convincing. Besides the administration of erythropoietin in preoperative blood
      donation the necessity of which is to be questioned as a routine measure due to
      the efficacy of apparative-technical methods, more distinct and more specific
      indications probably emerge for this pharmacological support: preoperative
      administration of erythropoietin in anemic patients incapable of donating an
      autologous predeposit, anemic patients unable to undergo an elective surgical
      intervention due to the severity of the pre-existing anemia, patients who refuse
      autologous predeposit as well as homologous blood transfusions for religious
      reasons, and finally short term perioperative (pre- and/or postoperative)
      administration for reducing the period and the extent of postoperative anemia.

PMID- 8148016
TI  - [The present possibilities for routine use of blood-saving measures from the
      anesthesiologic point of view--theoretical basis and clinical practice. I.
      Potential risks of homologous transfusion; normovolemic hemodilution].
AB  - This paper, which is the first part of four, deals with the potential risks of
      homologous blood transfusion as well as with normovolemic hemodilution, an
      autologous transfusion method, which is easily to be applied and not expensive.
      Although the various methods of autologous transfusion are well known for many
      years the public discussion on the "AIDS-topic" has led to a growing interest in
      blood-saving measures. However, in contrast to the so-called "AIDS-topic" the
      potential risks of a transfusion-transmitted hepatitis as well as the immunologic
      effects of homologous blood are of much greater importance. Moreover, high-court
      sentences give the legal background for intensifying autologous transfusion and
      to offer it to the patients. So far there are four autologous transfusion methods
      to be applied routinely: 1. normovolemic hemodilution (NHD); 2. intra- and/or
      postoperative blood salvage (I/PBS) with or without autologous direct
      retransfusion (ADR); 3. preoperative autologous plasmapheresis (PPH); 4.
      preoperative autologous blood donation (ABD). Moreover, drug-induced stimulation
      of the erythropoiesis by means of erythropoietin and the additional (intravenous)
      administration of iron may become a further component among autologous
      transfusion methods. Normovolemic hemodilution means exchange of autologous blood
      versus an artificial colloid. To make sure for normovolemia is to be considered a
      "conditio sine qua non" for "functioning" of normovolemic hemodilution.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8148017
TI  - [The efficiency of sterilization methods for different soils].
AB  - Three different soil types (two sandy materials and one till soil type) were
      sterilized with 14 different sterilization methods or variations. The cation
      exchange capacity and specific surface of the soil samples were chosen as control
      parameters of physico-chemical modifications in the soils. Incubation of soil
      samples in the presence of Na-azide and HgCl2, in addition to tyndallization and
      fractionated heating of soil lead to a significant reduction of microorganisms.
      UV radiation and alternating freezing and thawing of soil had no influence on the
      number of microorganisms. The application of mercury-II-chloride did not lead to
      the expected sterilization, especially with till. A sterilization of soil is
      possible by using formaldehyde and ethylene oxide gassing, in addition to
      autoclaving and gamma radiation. No microorganisms could be detected in the soils
      after application of these sterilization methods. The cation exchange capacity of
      the soils was only slightly influenced with these methods. The use of gamma
      radiation seems to be the best method for sterilization of soils.

PMID- 8148018
TI  - Assessment of some selective media for the recovery of Aeromonas hydrophila from
      surface waters.
AB  - A comparison was made of three different growing media already proposed by some
      authors for the recovery of Aeromonas hydrophila in environmental water samples
      of various origins. The media tested were Rippey and Cabelli m Aeromonas agar,
      Rimler-Shotts agar and the Ryan Aeromonas Base Medium with the addition of
      ampicillin. The efficiency of the three media was evaluated on the basis of the
      following reference criteria: accuracy, selectivity and specificity. The results
      obtained, analyzed by calculating the Kendall concordance coefficients,
      demonstrated that m Aeromonas agar is the most suitable media for quantitative
      recovery of Aeromonas hydrophila from surface water samples even if a reduction
      in the total heterotrophic load of 3-logs was never obtained with this medium.

PMID- 8148019
TI  - [Model tests for effectiveness assay of disinfectants on surfaces. III.
      Dependence of test results on the type of substances and the test microbes
      (Staphylococcus aureus, Mycobacterium terrae)].
AB  - A new test method for surface disinfectants was applied to investigate the
      efficacy of the most important active components of disinfectants to
      Staphylococcus aureus and Mycobacterium terrae. The test germs were embedded in
      coagulated blood. Frosted glass served as test surface. The disinfection was
      performed by applying a fixed amount of the disinfectant and mixing it with the
      contamination by rubbing. The number of surviving germs was determined
      quantitatively. Generally, the two test germs showed a distinctly different
      behaviour towards the active substances applied. Mycobacteria proved to be
      clearly more resistant than staphylococci, except with formaldehyde and the
      cresol-soap solution. The formaldehyde, the mycobacteria were only a little more
      resistant, while to cresol-soap solution they were even a little more sensitive
      than were staphylococci. Compounds containing active chloride showed a sufficient
      effect on mycobacteria only if the consumption of the active component by blood
      was nearly excluded. The quaternary ammonium compound and glyoxal, even the high
      concentrations, showed a totally insufficient efficacy to mycobacteria. The
      results shall provide the basis for a new guideline to be established by the
      Federal Health Office concerning the efficacy testing of surface disinfectants
      effective against mycobacteria, especially tuberculosis bacteria.

PMID- 8148020
TI  - Needed: technology for the masses.

PMID- 8148021
TI  - Using a computer color-matching system in color reproduction of porcelain
      restorations. Part 2: Color reproduction of stratiform-layered porcelain samples.
AB  - Computer color matching is an excellent method for reproducing certain colors of
      various objects using a spectrophotometer and a computer. In this study the
      authors attempted to reproduce the color of layered porcelain samples according
      to the computer color-matching formulation, wherein a computer color-matched
      sample is made and compared with the target sample. The color differences between
      the computer color-matched samples (opaque/dentin and opaque/dentin/enamel) and
      the target samples approximated 1.0, and the samples were indistinguishable by
      visual observation. The spectral reflectance curves were also very similar.

PMID- 8148022
TI  - The influence of temperature on the dimensional stability of poly (vinyl
      siloxane) impression materials.
AB  - It may be desirable to extend the working time of poly(vinyl siloxane) impression
      materials when making a multiple-unit impression. Alteration of the base-catalyst
      ratio is not possible with automix systems, but chilling the impression material
      provides an alternative. This study evaluated the dimensional accuracy of chilled
      impression material and the effect on accuracy of reheating the impression to
      mouth temperature prior to pouring. Two brands of poly(vinyl siloxane) impression
      material were evaluated both after refrigeration and at room temperature.
      Impressions were poured at room temperature and reheated to mouth temperature
      prior to pouring. Gypsum dies were recovered and measured. Refrigeration had no
      statistically significant effect on dimensional accuracy. Reheating the
      impression had no clinically significant effect on accuracy.

PMID- 8148023
TI  - A comparison of the accuracy of two removable die systems with intact working
      casts.
AB  - This study evaluated the reproducibility of die position using two removable die
      systems and two die stones. Poly(vinyl siloxane) impressions were made of a
      stainless steel, U-shaped arch with four evenly spaced abutments. Six groups were
      evaluated: Zeiser system/Fuji Rock; Zeiser system/Die Keen; solid cast/Fuji Rock;
      solid cast/Die Keen; Fuji Rock/Pindex; and Die Keen/Pindex. An optical comparator
      was used to measure the height of each abutment, the distance between the
      anterior abutments, and the distance between the posterior abutments. The Zeiser
      system with either Fuji Rock or Die Keen yielded the greatest accuracy. Die Keen
      exhibited more linear expansion than Fuji Rock, and solid casts had less
      distortion than the Pindex system.

PMID- 8148024
TI  - Using cephalometry to evaluate maxillomandibular relationships in complete
      denture construction.
AB  - Long-term denture wearers undergo facial changes as a result of occlusal wear of
      the dentures and residual ridge resorption. This study examined 12 such patients,
      presenting with a clinical appearance of Angle's Class III occlusal
      relationships, to evaluate a clinical method of determining the correct
      mandibular position. Complete dentures were fabricated for each patient using
      standard clinical procedures, but acrylic resin blocks were left on the
      mandibular posterior bases instead of denture teeth. Ensuing changes in
      maxillomandibular relationships were recorded. After the stabilization of the
      mandibular relationship, the dentures were completed using mandibular posterior
      teeth. Patients were evaluated using cephalometric analysis before and after
      treatment. Results show that a careful procedure of denture fabrication allows
      the determination of the correct mandibular relationship, even in patients who
      have experienced extreme facial collapse.

PMID- 8148025
TI  - Fracture toughness of high alumina core dental ceramics: the effect of water and
      artificial saliva.
AB  - The fracture toughnesses of two high alumina core ceramics were determined by
      using the single edge notched specimen method. Measurements were made in air,
      water, and artificial saliva. Fracture toughnesses of 1.89 and 1.75 MPa.m1/2 were
      obtained for Cerestore and Vitadur N samples, respectively, tested in air. Values
      obtained from Vitadur N samples that were tested in deionized water were
      significantly lower than those that were measured in air. Values for samples of
      both ceramics that were tested in artificial saliva were not significantly
      different from those that were tested in air. The fracture mode was a combination
      of intergranular and transgranular for Cerestore and predominantly transgranular
      for Vitadur N.

PMID- 8148026
TI  - Early erosion of glass-ionomer cement at crown margins.
AB  - This study investigated the early erosion of glass ionomer-cement that had been
      used to lute complete cast crowns. Restorations had margins ending on either
      enamel or cementum and had various sizes of marginal openings. These restorations
      were compared to those using a standard zinc phosphate cement. Results showed
      that leaving the band of excess cement, expressed during the seating of the
      crown, undisturbed for 10 minutes prevented significant erosion in a wet field. A
      resin coat was not necessary to provide further protection after removal of the
      band. Zinc phosphate cement also showed significant early erosion when exposed to
      moisture.

PMID- 8148027
TI  - Effect of dissolution on color of extrinsic porcelain colorants.
AB  - The effect of in vitro dissolution in acidulated phosphate-fluoride gel on the
      color of metal ceramic samples having surface metal oxide colorants was
      determined. Three different colorants were applied using two techniques at two
      different firing temperatures. The color difference was most apparent when the
      colorant and glaze were combined with only one firing cycle. All colorants
      increased in value, but changes in color difference were most evident with the
      blue colorant. It was concluded that dissolution in acidulated phosphate-fluoride
      gel does affect the color of extrinsic metallic oxide colorants.

PMID- 8148028
TI  - Numeric approach to the biomechanical analysis of thermal effects in coated
      implants.
AB  - A two-dimensional, finite element method was used to examine the influence of
      material selection and suprabony exposure of the implant coating on thermal and
      mechanical stress distribution. Hydroxyapatite coating reduced the heat
      conduction to the surrounding tissue because of its low thermal conductivity.
      However, thermal stress resulted from thermal expansion of the hydroxyapatite and
      titanium core. This might influence the success of hydroxyapatite-coated implants
      because the biomechanical properties of ceramics are so poor for tensile and
      shearing stress. In addition, this tendency becomes more pronounced when the
      hydroxyapatite coating surface extends beyond the cortical bone.

PMID- 8148029
TI  - A rapid three-dimensional measurement system for facial morphology by laser multi
      slits.
AB  - A laser light-sectioning technique for measuring the three-dimensional shape of
      the face has been developed. Multi-slit lasers were used to minimize the
      recording time, and the accumulating technique of multiple images was used to
      reduce the memory size. The system can scan the entire human face within 6
      seconds and develop a three-dimensional image in approximately 4 minutes. The
      accuracy of this system was found to be within a 0.4% relative error. The method
      has the advantages of being contact-free, rapid, automatic, and useful for three
      dimensional clinical assessment.

PMID- 8148030
TI  - Microleakage associated with resin composite-cemented, cast glass ceramic
      restoration.
AB  - Resin cements are the preferred luting media for ceramic restorations, but
      manufacturers have traditionally made no recommendations concerning the use of
      dentin bonding agents in the luting process. This in vitro study evaluated the
      microleakage associated with several luting agents for ceramic inlays. One
      hundred twenty Class V inlays (occlusal margins in enamel and gingival margins in
      dentin) were luted in extracted teeth using zinc phosphate cement, two resin
      cements without a bonding agent, and two resin cements with three dentin bonding
      agents. This study suggests that the use of a dentin bonding agent with a resin
      cement will reduce microleakage in cast glass-ceramic restorations.

PMID- 8148031
TI  - Marginal fit of restorations before and after cementation in vivo.
AB  - Triturated luting cements provide convenient clinical handling. This study
      clinically evaluated the influence of two trituration capsule cement systems on
      the marginal fit of inner copings for telescoping crowns. Using a randomized
      parallel design, one coping was cemented using zinc phosphate cement (Phosphacap)
      and one using a glass-ionomer cement (Ketac-Cem Maxicap) for each of 12 patients.
      A blind examination of the marginal fit of the restorations was made before and
      after cementation using the replica technique and a scanning electron microscope.
      The mean marginal discrepancies for all cast copings were approximately 30
      microns (median 23 microns) before cementation. They increased significantly
      after cementation to 86 microns (median 63 microns) in the zinc phosphate cement
      copings but to only to 47 microns (median 44 microns) in the glass-ionomer cement
      copings.

PMID- 8148032
TI  - Prothymosin alpha mRNA is expressed in competent and proliferating rat thyroid
      cells (FRTL-5) but is not sufficient to elicit cell progression through the cell
      cycle.
AB  - Using flow cytometry we observed the effects that different hormonal treatments
      had on the progression of rat thyroid (FRTL-5) cells through the cell cycle. The
      absence of hormones or the addition of TSH (6 mU/ml) did not induce DNA
      synthesis; however, the addition of IGF-I (30 ng/ml) promoted cell proliferation.
      The number of cells recruited by IGF-I was lower than when IGF-I and TSH were
      used. We therefore concluded that we had a model with three different types of
      cells: (1) quiescent cells, cells cultured in the absence of hormones, considered
      to be G0-arrested cells, (2) competent cells, TSH-treated cells that did not
      proliferate (being arrested in a cycle phase different from G0) and (3) actively
      proliferating cells, cells treated with TSH plus IGF-I. Prothymosin alpha (PTA)
      mRNA levels were almost undetectable in cells cultured without hormones at all
      times studied, i.e. 8, 14 and 24 h. On the contrary, TSH and/or IGF-I greatly
      increased PTA mRNA. These data indicate that G0-arrested quiescent cells do not
      express PTA mRNA and that PTA mRNA is induced when FRTL-5 cells are committed to
      proliferate by the addition of TSH, in spite of being arrested by the lack of IGF
      I. We therefore conclude that PTA mRNA expression may be an event that is
      necessary for cells to proliferate, but that it is not sufficient for the
      promotion of cell progression through the cell cycle.

PMID- 8148033
TI  - The hepatic receptor for sex steroid-binding protein: study on a non-malignant
      cell line (Chang liver).
AB  - The binding of human sex steroid-binding protein (SBP), labelled with 125I, was
      studied on whole cultured liver cells (Chang liver cells). SBP was shown to bind
      to a receptor site on normal hepatocytes. The binding was time- and temperature
      dependent, highly specific and of high affinity. The liver receptor recognizing
      SBP was demonstrated to be different from the asialoglycoprotein receptor; in
      addition, laminin, which is structurally related to SBP, could not bind to the
      receptor. SBP was shown to recognize two binding sites with different affinities;
      the low affinity site was shown to possess a remarkably high capacity. This
      characteristic, which until now has been described only for hepatocytes, could be
      related to the unique role of the liver with regard to both SBP and sex steroids.

PMID- 8148034
TI  - Molecular cloning of cDNAs encoding two types of gonadotrophin alpha subunit from
      the masu salmon, Oncorhynchus masou: construction of specific oligonucleotides
      for the alpha 1 and alpha 2 subunits.
AB  - Two types of cDNA (GTH alpha 1 and -alpha 2) encoding the alpha subunits of masu
      salmon (Oncorhynchus masou) gonadotrophin were cloned by the reverse
      transcription-polymerase chain reaction for pituitary mRNAs. The nucleotide
      sequences showed that the GTH alpha 1 cDNA was 380 bp long, encoding 119 amino
      acids, and that GTH alpha 2 cDNA was 365 bp long, encoding 114 amino acids. The
      masu salmon alpha subunit types had a few differences between the sequences, with
      homologies of 80% (nucleotide sequence) and 72% (amino acid sequence). The
      structural difference between the alpha 1 and alpha 2 subunits was predicted
      using hydropathic analysis. The evolutionary interval between masu and chum
      salmon was estimated to be 4.0 and 2.3 million years by comparing their GTH alpha
      1 and -alpha 2 subunits respectively. These time values are roughly consistent
      with the evolutionary time interval (3.0 million years) estimated from fossil
      records and an isozyme study. Specific synthetic oligonucleotide probes were
      constructed and used for genomic Southern blot analyses. The restriction fragment
      sizes of the GTH alpha 1 and -alpha 2 genes were similar, and when their patterns
      were compared with those from four other teleosts, each species showed a
      different pattern from the others, but no difference between their respective
      alpha 1 and alpha 2 genes. Therefore, the structural features of the GTH alpha 1
      and -alpha 2 genes may have diverged in a similar manner in these five teleosts.

PMID- 8148035
TI  - Molecular cloning of cDNAs encoding two gonadotrophin beta subunits (GTH-I beta
      and -II beta) from the masu salmon, Oncorhynchus masou: rapid divergence of the
      GTH-I beta gene.
AB  - Two types of cDNA (GTH-I beta and -II beta) encoding the beta subunit of masu
      salmon (Oncorhynchus masou) gonadotrophin were cloned using the reverse
      transcription-polymerase chain reaction for pituitary mRNAs. The nucleotide
      sequence of GTH-I beta cDNA was 469 bp long, encoding 137 amino acids, and GTH-II
      beta cDNA was 476 bp long, encoding 142 amino acids. These two masu salmon beta
      subunit types showed low homologies of 52% (nucleotide sequence) and 33% (amino
      acid sequence). The evolutionary interval between masu and chum salmon was
      estimated to be 5.65 and 1.43 million years by comparing GTH-I beta and GTH-II
      beta respectively. These time values are markedly inconsistent with the
      evolutionary time (3.0 million years) estimated from fossil records and an
      isozyme study. Southern blot analyses showed that the I beta gene restriction
      fragment lengths differed among five teleosts, whereas, with one exception, the
      II beta gene showed well conserved patterns. Therefore, the GTH-I beta gene may
      have diverged at a faster rate than the GTH-II beta gene.

PMID- 8148036
TI  - Expression of Pit-1 and related proteins in diverse human pituitary adenomas.
AB  - Pit-1, a member of the POU family of homeo-domain transcription factors,
      activates prolactin and GH gene expression but also has a role in pituitary cell
      differentiation and proliferation. Expression of Pit-1 may therefore be of
      central importance in the function and phenotype of human pituitary adenomas. We
      have found evidence that, in addition to Pit-1 mRNA, Pit-1-like immunoreactivity
      and DNA-binding activity are readily detectable in a series of human pituitary
      adenomas. Gel mobility shift assays using adenoma protein extracts with two Pit-1
      binding sites from the human prolactin gene promoter demonstrated the formation
      of several DNA sequence-specific protein-DNA complexes; some of these could be
      accounted for by Oct-1-binding activity. Pit-1 activity was anticipated in
      prolactin- and GH-secreting adenomas, but was also detected in a proportion of
      endocrine-inactive (non-secreting) adenomas that did not express Pit-1 target
      genes. The data demonstrate the presence of Pit-1 in a range of pituitary
      adenomas. Different adenomas generated slightly differing patterns of DNA-binding
      activity, though Pit-1 mRNA and protein size appeared normal in all tumours so
      far examined.

PMID- 8148037
TI  - Influence of growth factors on the plasminogen activator activity of avian
      granulosa cells from follicles at different maturational stages of preovulatory
      development.
AB  - Granulosa cells from the first (F1), third (F3) and fifth and sixth (F5-6)
      preovulatory follicles and the small yellow follicles (SYFs; diameter 6-8 mm)
      were cultured for 21 h in the absence and presence of murine and human epidermal
      growth factors, fibroblast growth factor, transforming growth factors alpha and
      beta-I (TGF alpha, TGF beta), platelet-derived growth factor and insulin-like
      growth factor-I at concentrations of 0.1-100 ng/ml. Plasminogen activator (PA)
      activities in the cell (PAc) and in the medium (PAm) were measured by
      fibrinolysis and fibrin overlay methods. Basal PAc and PAm activities were
      highest in cell cultures from the less mature follicles (F5-6 and SYF) and
      decreased as the follicles matured (F3 > F1). PAc activity was greater than PAm
      activity, irrespective of the stage of follicular development. All growth factors
      examined at the 100 ng/ml level were effective in increasing PAc and PAm
      activities in cultures of granulosa cells from F1 follicles. However, only TGF
      alpha was able to increase PA activities at lower concentrations. The stimulation
      of the PA activities of granulosa cells from F3 follicles was inconsistent. None
      of the growth factors significantly increased PA activities in granulosa cells
      from F5-6 follicles and SYFs, as determined by fibrinolysis. The major PAc and
      PAm species (characterized by fibrin overlay) had a molecular mass of about 35
      kDa, which is characteristic of the urokinase type. Both assay methods detected a
      stimulatory effect of the growth factors on PA activities in the granulosa cells
      from F1 follicles. However, an increase in PA activities in cells from F3 and F5
      6 follicles and SYFs was indicated only after fibrin overlay analysis. Tritiated
      thymidine was incorporated into the DNA of granulosa cells at all stages of
      follicular development and was enhanced by all growth factors, although TGF alpha
      and TGF beta were the most effective and had a ranked order of activity: F3, F5-6
      > F1, SYF. The present findings show that, of the growth factors examined, TGF
      alpha may be an effective regulator of PA activity in avian granulosa cells
      during follicular development, in addition to its observed mitogenic action.

PMID- 8148038
TI  - Differential expression of non-allelic insulin genes in rodent islet tumour
      cells.
AB  - We have compared the expression patterns of the non-allelic insulin 1 and 2 genes
      during prolonged in-vitro culture of the mouse islet cell line beta-TC3, where
      transformation by the SV40 T oncoprotein is targeted to the differentiated beta
      cell phenotype, and the rat islet cell line NHI-6F, in which the beta-cell
      phenotype is induced by transient in-vivo passage. The NHI-6F clone carries, in
      addition, a single copy of a transfected silent human insulin gene which contains
      3 kb of regulatory sequences known to confer beta-cell-specific expression.
      Insulin gene expression was measured by an assay based on a reverse transcription
      polymerase chain reaction, to determine whether the ancestral rodent insulin 2
      genes (and the human homologue in the NHI-6F cells) are regulated differently
      from the duplicated rat and mouse insulin 1 genes. We have shown that activation
      of insulin gene expression in the NHI-6F cells includes transcriptional
      activation of all three genes, but that extended propagation of tumour cells in
      vitro leads to a selective and equal decline in the quantities of transcripts
      from the rat 2 and human genes relative to transcripts from the rat 1 gene. In
      the later passages, insulin transcripts were derived almost exclusively from the
      rat 1 gene. In early in-vitro passages of the mouse endocrine cell line beta-TC3,
      the expression pattern of the mouse 1 and 2 insulin genes resembled that seen in
      isolated mouse islets. After more than 45 in-vitro passages, expression of the
      duplicated mouse 1 gene decreased tenfold when compared with the ancestral mouse
      2 gene. As previously shown for NHI-6F cells, the differential expression of non
      allelic insulin genes in the beta-TC3 line was also clearly evident at the
      cellular level, where a subpopulation of cells selectively expressed readily
      detectable levels of mouse C-peptide 2 immunoreactivity while devoid of C-peptide
      1. Our results suggest that the maintenance of insulin gene expression in rodent
      tumour cells is influenced by enhancer sequences which are not shared by the
      ancestral and duplicated insulin genes, and that either species-specific
      conditions or transformation-related differences exist between the rat and mouse
      cell lines that govern which gene remains active during prolonged in-vitro
      propagation.

PMID- 8148039
TI  - Insulin-like growth factor-I mRNA expression in the interstitial cells of the rat
      testis.
AB  - IGF-I mRNA has been demonstrated in testicular tissue and, more recently,
      localized specifically to Leydig cells. This study investigated the expression of
      IGF-I and side-chain cleavage enzyme (SCC) mRNA in two preparations of rat
      interstitial testicular cells which were separated by buoyant density into Leydig
      cell-enriched and -depleted fractions. RNA was prepared from interstitial cells
      obtained from the testes of untreated adult and immature rats and adult rats
      treated with human chorionic gonadotrophin (hCG) or ethane dimethanesulphonate
      (EDS; to destroy Leydig cells). IGF-I mRNA was detected in all samples, with five
      major transcripts ranging from 7.5 to 0.6 kb. Leydig cells (3 beta-hydroxysteroid
      dehydrogenase-positive and sensitive to EDS) expressed abundant IGF-I and SCC
      mRNAs, and levels of both were increased following hCG treatment. However, in
      addition, IGF-I mRNA which was derived from non-Leydig interstitial cells was
      detected, in the complete absence of SCC message, either in the more buoyant
      interstitial cells or in both interstitial cell fractions following the
      destruction of Leydig cells by EDS treatment. IGF-I expression in the Leydig cell
      depleted cell fraction was also increased by hCG treatment, and it is therefore
      suggested that at least part of this non-Leydig interstitial cell IGF-I mRNA
      originates in Leydig cell precursors. In conclusion, Leydig cells are not the
      sole origin of IGF-I mRNA in the testis, and the non-Leydig cell expression may
      be an important component of testicular IGF-I production.

PMID- 8148040
TI  - Direct effect of adenosine on prolactin secretion at the level of the single rat
      lactotroph: involvement of pertussis toxin-sensitive and -insensitive transducing
      mechanisms.
AB  - We studied the effect of adenosine on prolactin secretion by the anterior
      pituitary, and the transduction mechanisms whereby the purine exerts its action.
      Adenosine inhibited prolactin release in basal and in vasoactive intestinal
      peptide (VIP)- or TRH-stimulated conditions. Pertussis toxin pretreatment reduced
      the inhibition of VIP-stimulated prolactin secretion which was induced by
      adenosine, while it completely abolished the effect of the purine on TRH-evoked
      prolactin release. In membrane preparations of anterior pituitary cells,
      adenosine reduced the adenylate cyclase activity stimulated by VIP. Such an
      inhibition was not blocked by pertussis toxin pretreatment. Furthermore, the
      purine reduced TRH-stimulated inositol phosphate production in cultured anterior
      pituitary cells, an effect that was reversed by pretreatment with pertussis
      toxin. In addition, the nucleoside did not significantly affect the TRH-induced
      rise in intracellular calcium. In conclusion, our data show that adenosine
      inhibits prolactin secretion, acting on purinergic receptors coupled to the
      adenylate cyclase enzyme and phospholipase C. The effect of the nucleoside on
      adenylate cyclase seems to be achieved either by the involvement of an adenosine
      receptor coupled to the catalytic subunit of the enzyme via a pertussis toxin
      sensitive G protein, or by the activation of a site directly coupled to the
      catalytic subunit of the adenylate cyclase (the P site). Its effect on
      phospholipase C seems to be mediated by a purinergic receptor coupled to the
      intracellular effector via a pertussis toxin-sensitive G protein.

PMID- 8148041
TI  - Insulin delivery by somatic cell gene therapy.
AB  - The feasibility of somatic cell gene therapy as a method of insulin delivery has
      been studied in mice. Murine pituitary AtT20 cells were transfected with a human
      preproinsulin DNA in a plasmid containing a metallothionein promoter and a gene
      conferring resistance to the antibiotic G418. The AtT20MtIns-1.4 clone of cells
      was selected because of its higher insulin-releasing activity compared with other
      clones. After culturing for 24 h in Dulbecco's medium containing 10 mM glucose,
      the AtT20MtIns-1.4 cells released human insulin at about 5 ng/10(6) cells per 24
      h. Insulin release was not significantly altered by raised concentrations of
      glucose, potassium or calcium, but insulin release was increased by 20 mM
      arginine, 5 mM isomethylbutylxanthine and 90 microM zinc. AtT20MtIns-1.4 cells (2
      x 10(6)) were implanted intraperitoneally into non-diabetic athymic nude (nu/nu)
      mice, and the mice were made diabetic by injection of streptozotocin after 7
      days. Release of human insulin in vivo was assessed using a specific plasma human
      C-peptide assay. Human C-peptide concentrations were maintained at about 0.1
      pmol/ml throughout the 29 days of the study. The development of streptozotocin
      induced hyperglycaemia was delayed in recipients of the cells releasing human
      insulin, compared with a control group receiving an implant of non-transfected
      cells. At autopsy the implanted AtT20MtIns-1.4 cells in each recipient had formed
      a tumour-like aggregation, with an outer region of insulin-containing
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148042
TI  - Cloning of a toad prolactin cDNA: expression of prolactin mRNA in larval and
      adult pituitaries.
AB  - A toad (Bufo japonicus) prolactin cDNA was specifically amplified from cDNAs
      constructed from the total RNA of adenohypophyses, employing the DNA polymerase
      chain reaction. Sequencing analysis revealed that the cDNA clone thus obtained
      was 602 bp in length, and encoded the C-terminal 134 amino acid residues of the
      toad prolactin molecule. The length of the toad prolactin mRNA was estimated to
      be about 1.0 kb by Northern blot analysis. The partial amino acid sequence
      deduced from the nucleotide sequence showed the following homologies between toad
      prolactin and the prolactins of other vertebrates: 69% with man, 80% with
      chicken, 81% with sea turtle, 91% with bullfrog and 38% with salmon. Using the
      cDNA as a probe, developmental and seasonal changes in prolactin mRNA levels in
      the pituitaries of toads were studied. Prolactin mRNA in the pituitary rose as
      metamorphosis progressed and declined at the end of metamorphosis. During the
      breeding season the pituitary content of prolactin mRNA was relatively high. This
      finding suggests that the increases in plasma and pituitary prolactin levels in
      larvae at metamorphic climax and in adults that remain in or migrate into water,
      as reported previously, accompany the increase in prolactin synthesis.

PMID- 8148043
TI  - Preparation and characterization of a recombinant DNA-derived ovine growth
      hormone variant internally labelled with sulphur-35.
AB  - 125I-Labelled polypeptide hormones have been extremely valuable for
      radioimmunoassays, receptor-binding studies and investigation of the processing
      and metabolism of hormones. However, such externally labelled material has the
      disadvantage that addition of one or more iodine atoms may alter the properties
      of the polypeptide. Furthermore, for studies on hormone metabolism and
      processing, the label may become separated from the hormone or its main breakdown
      products. Use of internally labelled polypeptides produced by biosynthesis can
      avoid such problems, but previously such material has usually been of low
      specific radioactivity, and unsuitable for many purposes. Here we describe the
      development of a procedure for the production of an internally labelled ovine GH
      analogue (oGH1) using a plasmid produced by recombinant DNA methods and
      expression in Escherichia coli. Bacteria were grown in medium containing a low
      sulphate concentration, and then incubated in medium containing 35SO4(2-) as the
      sole sulphur source. Under these conditions, the bacteria incorporated 35S into
      proteins including GH. Purification of such material required considerable
      modification of previously described methods, because of the need to handle very
      small amounts of highly radioactive material. The bacteria were lysed using
      lysozyme, and inclusion bodies were solubilized using 6 M guanidinium chloride.
      [35S]oGH1 was renatured and then purified by gel filtration on Sephacryl S-100,
      followed by immunoaffinity chromatography and a second gel filtration step.
      Material prepared in this way had a specific radioactivity of 6-27
      microCi/micrograms, and showed high 'bind-ability' to polyclonal and monoclonal
      antibodies and to receptors. 35S-Labelled material bound to receptors more
      effectively than 125I-labelled GH and showed improved stability.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8148044
TI  - [Cross allergies].
AB  - The first descriptions of crossed allergenicity were concerned with the
      associations between Pollen/Food allergy: birch pollen/apple, grass pollen/wheat
      tomato etc. Since then other crossed reactions have been described, involving
      pneumoallergens, tropallergens, drugs, hymenoptera venoms. Crossed reactions are
      the combination of an antigen with a recognition molecule other than that which
      stimulated its synthesis, because of epitope(s) that are common or sufficiently
      close between two antigens. The techniques of immunoprints and RAST inhibition
      give confirmation of crossed reactions that are suspected clinically.

PMID- 8148045
TI  - [Nocturnal spasmodic cough in the infant. Evolution after antireflux treatment].
AB  - Several studies have shown the relationship between gastro-oesophageal reflux,
      bronchial asthma and chronic nocturnal cough and this should not be neglected,
      particularly in patients who present an unfavourable development in spite of
      conventional treatment. For diagnosis of gastroesophageal reflux, amongst other
      investigations, esophageal gammagraphy of swallowing, that detects alterations in
      the mobility of the oesophagus, secondary to a possible oesophagitis. The
      objective of this study was to evaluate the clinical progress and gammagraphy of
      a group of children with chronic predominantly nocturnal cough (with or without
      bronchial asthma) with initially pathological esophageal gammagraphy, after three
      months of treatment with gastrokinetic drugs (cisapride against domperidone) and
      postural dietetic limits, in comparison with a reference group who, although
      having followed the limits in question had not received the pharmacological
      treatment. From the clinical viewpoint, cough disappeared in 64.5% of cases
      without significant statistical differences between the two groups. Gammagraphy
      became normal in 20/55 cases, improved in 10/55 cases and was unchanged in 25/55.
      Although there was no significant difference, gammagraphy development was better
      in children who received domperidone. The agreement between clinical progress and
      gammagraphy was 60% with a large number of false positives in the gammagraphy. We
      believe that the simple introduction of the postural-dietetic measures may
      improve the clinical control in the type of patients who present with a chronic
      nocturnally predominant cough that does not yield to conventional treatment.

PMID- 8148046
TI  - [Desensitization with grass pollens: a review of the literature].

PMID- 8148047
TI  - [State of the art on allergy to the cat: a review of the literature].
AB  - There are now seven cat allergens. The major, Feld is present in squames, skin
      and urine, but not in serum albumin. Recent studies have shown that its base is
      in sebum. It can float in the atmosphere on very small, light particles
      indefinitely and is deposited on clothes, curtains and carpets in considerable
      amounts. Immunotherapy, often the cause of collateral accidents, in the best
      cases only gives a transitory reduction of conjunctival and pituitary
      sensitisation. It has no proven activity in asthma and the biological data do not
      change logically during treatment. Prevention consists of total exclusion, which
      is very difficult to effect.

PMID- 8148048
TI  - ["Alternaria": a review of the literature].

PMID- 8148049
TI  - [Desensitization against the venoms of hymenoptera: a review of the literature].
AB  - Use of purified Hymenoptera venom extracts in desensitization protocols has made
      it possible to show its efficacy and tolerance in patients who have presented
      with a generalised serious reaction following Hymenoptera stings. In spite of a
      partial consensus, there are still points for discussion about the indications
      and especially about the stop criteria, which must be studied case by case.
      Different studies that compare batches of desensitized patients with others who
      have been not insufficiently treated, all confirm the best protection of
      subjects, even if in each batch there are exceptions that tend to qualify
      optimistic results.

PMID- 8148050
TI  - [Cross allergies: latex-food].

PMID- 8148052
TI  - Characterization of cell lines derived from formaldehyde-induced nasal tumors in
      rats.
AB  - Cell lines derived from formaldehyde-induced nasal tumors in Fischer 344 rats
      were established. All of the lines were found to be epithelial and aneuploid and
      to express keratin, transforming growth factor-alpha, and epidermal growth factor
      receptor transcripts. Two of four lines were tumorigenic upon injection into nude
      mice, and these lines also contained point mutations in the p53 suppressor gene.
      The data indicate that these lines possess characteristics that make them a
      valuable tool for the study of chemically induced respiratory tract
      carcinogenesis.

PMID- 8148051
TI  - Inhibition of hepatitis B virus surface antigen gene expression in carcinogen
      induced liver tumors from transgenic mice.
AB  - We previously showed that hepatitis B surface antigen (HBsAg)-producing
      transgenic mice were more sensitive to hepatocarcinogens than their normal
      littermates were. We have now investigated the regulation of hepatitis B virus
      (HBV) gene expression in carcinogen-induced liver tumors of HBV-carrier
      transgenic mice and in three cell lines derived from tumor samples. Transcription
      of the S gene was repressed in 17 tumors even though they had normal levels of
      liver-specific mRNAs such as albumin and transferrin. Three hepatoma cell lines,
      derived from independent tumor samples, were analyzed for their capacity to
      express the S gene after transfection of cloned DNA. Although they no longer
      expressed the endogenous S gene, they were still able to express it from
      transfected viral DNA both transiently and stably. The loss of HBsAg expression
      in tumors and in the cell lines was accompanied by de novo methylation of the S
      region, which is a way to permanently repress gene expression. Our data confirm
      in an animal model previous observations of S-gene expression in human
      hepatocarcinoma and suggest a role for its downregulation in tumor progression.

PMID- 8148054
TI  - In vitro and in vivo acceleration of the neoplastic phenotype of a low
      tumorigenicity rat bladder carcinoma cell line by transfected transforming growth
      factor-alpha.
AB  - We conducted an experiment to determine whether expression of transforming growth
      factor-alpha (TGF-alpha) enhances tumorigenicity in a low-tumorigenicity rat
      bladder carcinoma cell line and whether it is sufficient to induce a tumorigenic
      phenotype in a nontumorigenic rat bladder cell line. D44c cells (which are
      nontumorigenic) were derived from a minute nodule from a bladder treated with N
      methyl-N-nitrosourea (MNU); G1-200 cl-17 cells (which have low tumorigenicity)
      were isolated from D44c cells exposed to MNU in vitro. Neither cell line
      expressed TGF-alpha mRNA. The cells were cotransfected with pSV2neo and pSR alpha
      rTGF-alpha. The latter plasmid contains the rat TGF-alpha cDNA under the
      transcriptional control of the SR alpha promoter. In the low-tumorigenicity G1
      200 cl-17 cells, the expression of TGF-alpha mRNA and the subsequent synthesis of
      TGF-alpha protein activated epidermal growth factor receptors (EGFRs) and
      markedly enhanced tumorigenicity in nude mice (i.e., shortened the latency period
      before tumor appearance, accelerated the rate of growth, and increased the size
      of the tumors) as well as anchorage-independent growth in vitro. In
      nontumorigenic D44c cells, however, transfected TGF-alpha did not induce either
      anchorage-independent growth or tumorigenicity in nude mice, in spite of
      overexpression of EGFR mRNA and the constitutive expression of c-jun and junB
      mRNA. These results suggest that the increased signal transduction mediated by
      TGF-alpha enhanced tumorigenicity in a cell that was already tumorigenic but was
      not sufficient to induce tumorigenicity in a nontumorigenic cell.

PMID- 8148053
TI  - Influence of DNA repair by ada and ogt alkyltransferases on the mutational
      specificity of alkylating agents.
AB  - We investigated the influence of the alkyltransferases (ATases) encoded by the
      ada and ogt genes of Escherichia coli on the mutational specificity of alkylating
      agents. A new mutational assay for selection of supF- mutations in shuttle-vector
      plasmids was used. Treating plasmid-bearing bacteria with N-methyl-N-nitrosourea
      (MNU), N-ethyl-N-nitrosourea (ENU), and ethyl methanesulfonate (EMS) dramatically
      increased the mutation frequency (from 33-fold to 789-fold). The vast majority of
      mutations (89-100%) were G:C-->A:T transitions. This type of mutation increased
      in ada- (MNU) or ogt- (ENU) bacteria, suggesting that repair of O6-methylguanine
      by ada ATase and repair of O6-ethylguanine by ogt ATase contribute mainly to the
      decrease in G:C-->A:T transitions. The analysis of neighboring base sequences
      revealed an overabundance of G:C-->A:T transitions at 5'-GG sequences. The 5'-PuG
      bias increased in ATase-defective cells, suggesting that these sequences were not
      refractory to repair. G:C-->A:T transitions occurred preferentially in the
      untranscribed strand after in vivo exposure. That this strand specificity was
      detected even in bacteria devoid of ATase activity (ada- ogt-) and not after in
      vitro mutagenesis suggests a bias for damage induction rather than for DNA
      repair. Highly significant differences were found between the in vivo and in
      vitro incidences of G:C-->A:T substitutions at the two major hotspots, positions
      123 (5'-GGG-3'; antisense strand) and 168 (5'-GGA-3'; sense strand). These
      results are explained by differences in the probability of formation of stem-loop
      structures in vivo and in vitro.

PMID- 8148055
TI  - Altered expression of transforming growth factor-beta 1 mRNA and protein in mouse
      skin carcinogenesis.
AB  - Transforming growth factor (TGF)-beta 1, whose gene is located on mouse
      chromosome 7, has been proposed to be involved in skin carcinogenesis. In the
      study presented here, we demonstrated that single topical treatments with
      different types of tumor promoters, i.e., the protein kinase C activator 12-O
      tetradecanoylphorbol-13-acetate (TPA, 2 micrograms); the non-protein kinase C
      activators anthralin (22.6 micrograms), benzoyl peroxide (20 mg), and cumene
      hydroperoxide (1.2 mg); the first-stage tumor promoters 4-O-methyl-TPA (500
      micrograms) and A23187 (166 micrograms); and the second-stage tumor promoter
      mezerein (2 micrograms) produced transient induction of TGF-beta 1 mRNA in SSIN
      (inbred SENCAR) mouse skin. The time of maximum induction varied from 3 to 12 h;
      the relative extent of induction was ranked as cumene hydroperoxide > benzoyl
      peroxide > anthralin > TPA > 4-O-methyl-TPA > mezerein > A23187. These findings
      suggested that TGF-beta 1 mRNA induction is a common response of skin to several
      types of complete and stage-specific promoters; however, the extent of induction
      did not correlate with the reported hyperplastic activity of single applications
      of these promoters. We also demonstrated that TGF-beta 1 mRNA expression in
      papillomas of SENCAR mice generally correlated with expression levels of cyclin
      D1, another gene on chromosome 7, and with stage of tumor progression. TGF-beta 1
      mRNA expression was constitutively elevated in most squamous cell carcinomas from
      either initiation-promotion or complete carcinogenesis protocols. Cell lines
      established from carcinomas also overexpressed TGF-beta 1 mRNA.
      Immunohistochemical staining of tissue sections of normal and TPA-treated skin
      revealed the presence of extracellular TGF-beta 1 protein in the dermis and
      intracellular TGF-beta 1 protein in the epidermis, especially in the suprabasal
      layers. The staining patterns of papillomas varied, with 62 +/- 13% of the tissue
      showing strong intracellular staining but only 25 +/- 8% of the connective tissue
      staining for extracellular TGF-beta 1. Variable staining patterns were also found
      in carcinomas; some areas stained heavily for both the intracellular and
      extracellular forms of TGF-beta 1. Overall, 28 +/- 6% of the tissue of the 12
      analyzed carcinomas stained for the intracellular form and 18 +/- 5% for the
      extracellular form of TGF-beta 1.

PMID- 8148056
TI  - Mutations and expression of the p53 gene in rat bladder carcinomas and cell
      lines.
AB  - Abnormalities of the p53 gene are frequently observed in human tumors, including
      urinary bladder carcinoma, suggesting that p53 plays an important role in human
      carcinogenesis. However, its role in rat bladder carcinogenesis is unclear. We
      investigated p53 gene mutations and expression in rat urinary bladder
      carcinogenesis in vivo and in vitro. Fifteen urothelial cell lines, including six
      untransformed (nontumorigenic) ones, six transformed (tumorigenic) in vitro, and
      three derived from tumors induced in vivo, were examined for p53 expression by
      immunochemical analysis and for p53 mutations; in addition, 81 rat bladders were
      analyzed immunohistochemically for p53 expression, and 23 rat bladder tumors were
      analyzed for p53 mutations. Four cell lines had mutations in the p53 gene. Two of
      these were missense point mutations, and the other two were splicing mutations.
      On the other hand, no mutations were found in the bladder tumors induced in rats.
      By immunoprecipitation with PAb240, which is supposed to be specific for mutant
      p53, we detected mutations in three of the cell lines; PAb240 did not react with
      wild-type p53. However, in all cell lines and in growing populations of primary
      cultured bladder urothelial cells, p53 expression was detected
      immunohistochemically or by western blotting using PAb240 or PAb 421 monoclonal
      antibodies. In a high percentage of transitional cell carcinomas, wild-type p53
      expression was detected by immunohistochemical analysis with PAb240. These
      results suggest that p53 gene mutations may not occur frequently in rat bladder
      carcinogenesis in vivo but may occur in vitro and that p53 overexpression
      detected immunohistochemically is common and may be related to cell proliferation
      rather than to the presence of mutations in rat bladder carcinogenesis.

PMID- 8148057
TI  - Percutaneous transluminal coronary angioplasty: advances in technology and
      implications for nursing practice.

PMID- 8148058
TI  - Understanding post operative psychosis and sleep deprivation: a case approach.
AB  - The care of a critically ill, intensive care unit patient dangerously out of
      touch with reality, is a challenge requiring exceptional problem solving skills.
      This article will discuss the nursing management of a distressing, unusual case
      of post-operative psychosis. Specifically, this case involved a patient who
      suddenly became psychotic on his first post-operative day after having an atrial
      septal defect repair. The patient's self-destructive actions and the innovative
      strategies used by nursing staff to effectively intervene are described.
      Discussion of the complex interrelationship of factors that contributed to this
      patient's erratic behaviour is highlighted. Questions about the effects of sleep
      deprivation are raised.

PMID- 8148059
TI  - Sleep: a reality or dream for the hospitalized adult?
AB  - Nursing research literature is examined to determine the extent of sleep loss for
      the hospitalized adult. Research from the patient's perspective, nurses'
      assessment of patient's sleep and somnographic studies are considered. Although
      these three methods are inconsistent in the exact extent of sleep loss, all
      suggest that hospitalized patients experience less sleep than their normal
      pattern. Reasons for patients losing sleep are explored. Environmental factors in
      critical care areas are the most cited reason for loss of sleep yet other reasons
      are suggested. Consequences of sleep loss are explored. Some nursing
      interventions offered in the existing literature are examined for their
      feasibility. Finally, directions for future research are offered from this review
      of the literature.

PMID- 8148060
TI  - Understanding mediastinitis: nursing's role in prevention and treatment.
AB  - Mediastinitis is a clinical problem seen in patients after a mediasternotomy
      usually following cardiac surgery. Although relatively rare, this complication
      slows recovery, lengthens hospital stay and increases health care costs. An
      overview of the problem of sternal wound infection after cardiac surgery is
      provided. Predisposing, intraoperative and post-operative factors related to this
      problem will be discussed. Attention to the factors related to the problem may
      contribute to the prevention of mediastinitis. Clinical recognition of the
      problem will be described and treatment options, nursing therapeutics and
      research questions will be addressed.

PMID- 8148061
TI  - Development of an instrument to assess patient knowledge of cardiac
      catheterization.
AB  - The purpose of this article is to describe the development of a valid and
      reliable method of assessing patients' knowledge of cardiac catheterization. The
      findings of test-retest reliability, equivalence reliability as well as content
      and construct validity strongly support the validity and reliability of two
      cardiac catheterization knowledge questionnaires.

PMID- 8148062
TI  - Action research: a useful strategy for combining action and research in nursing?

PMID- 8148063
TI  - Some deleterious effects of intravenous dipyridamole in the presence of chronic
      lung disease.

PMID- 8148064
TI  - Uncertainty, and appraisal in patients diagnosed with abdominal aortic aneurysms.
AB  - The purpose of this study was to describe the uncertainty of subjects diagnosed
      with abdominal aortic aneurysms and to examine the relationship between
      uncertainty and subjects', positive or negative appraisals of uncertainty. Twenty
      seven subjects who had a definitive diagnosis of abdominal aortic aneurysms were
      surveyed using the Mishel Uncertainty in Illness Scale (MUIS), the Folkman and
      Lazarus Restructured Appraisal Scale, and a demographic questionnaire. Findings
      from the study suggested that the level of uncertainty among patients with
      abdominal aortic aneurysms was similar or higher than the level of uncertainty
      that has been reported for patients with myocardial infarctions (M = 91.9, S.D. =
      19.56). There was no significant relationship between uncertainty and appraisal
      of uncertainty as a danger (r = .21, p = .14) or opportunity (r = .14, p = .25).
      Implications for further research include examining patients uncertainty levels
      and appraisal at repeated intervals during their illness trajectory.

PMID- 8148065
TI  - A roadmap for the novice researcher.
AB  - This article outlines the research process as it applies to nurses in clinical
      practice. While the topic seems intimidating at first, by questioning clinical
      practice and maintaining an open mine, nurses can generate the enthusiasm and
      commitment necessary to conduct their own research. First, a nursing research
      issue worthy of investigation needs to be identified and thoroughly reviewed in
      the literature. The nurse next needs to bring together an appropriate research
      team and develop a formal research proposal. The team then submits the proposal
      through the organizational structure that grants approval and provides funding.
      Once the study has been implemented and the data collection is complete, the
      research team must decide on the best method of disseminating the research
      findings to nursing colleagues. This last important step helps to expand and
      build nursing's professional body of knowledge, and ensures that current nursing
      practice is based on valid research findings.

PMID- 8148066
TI  - The role of transdermal nicotine therapy in smoking cessation.
AB  - Despite repeated health warnings, cigarette smoking continues to cause
      significant morbidity and mortality to society. This may be attributal in large,
      to the addictive properties of nicotine and the withdrawal symptoms following
      smoking cessation. A clearer understanding of nicotine addiction has introduced
      new approaches to its treatment. This article will review the symptoms and
      treatment of nicotine addiction and withdrawal, with a particular focus on the
      role of the nicotine transdermal systems.

PMID- 8148067
TI  - Is your patient too old for cardiac surgery?

PMID- 8148068
TI  - Family protectiveness: a response to ischemic heart disease.
AB  - The concept of family protectiveness is described in the context of a family
      systems nursing approach to families experiencing chronic ischemic heart disease.
      Following a review of the literature, the concept is defined as a defensive
      response to guard the family against injury and loss, whereby the ill family
      member is the recipient of preferential treatment, and whereby at least one
      family member covers for the ill family member by taking temporary charge of
      responsibility for health maintenance and household activities. Family
      protectiveness is compared and contrasted to family support. Examples of
      criterion for measurement of family protectiveness for nursing research are
      proposed. Implications for nursing practice and nursing intervention research are
      discussed.

PMID- 8148069
TI  - Role patterns and emotional responses of women with ischemic heart disease 4 to 6
      weeks after discharge from hospital.
AB  - Women comprise only a small percentage of subjects in studies of psychosocial
      responses to heart disease. Some research suggests women have higher rates of
      anxiety and depression post myocardial infarction than men. This descriptive
      correlational study examined role enactment and emotional responses of nineteen
      women with ischemic heart disease four to six weeks after discharge from
      hospital. More specifically, the study examined the relationship among Physical
      Symptoms, Quality of Role Enactment, and Emotional Response. Study findings
      suggest subjects were generally satisfied with their role enactment. There were
      no relationships among the three study variables-Physical Symptoms, Quality of
      Role Enactment, and Emotional Response. However, women who experienced a
      myocardial infarction and those with other forms of ischemic heart disease
      differed in terms of physical symptoms and role enactment after discharge.
      Subjects did not report high levels of depression; yet, there was some indication
      of emotional distress. Interestingly, the first two weeks after discharge were
      described as the most difficult time. The results from this study point to areas
      of further research.

PMID- 8148070
TI  - Mid-term results with cultured epidermal autografts, allogenic skin transplants
      and cyclosporin A medication.
AB  - Transplantation of allogenic split thickness skin grafts (STSG) and
      immunosuppression with cyclosporin A enable early and definitive skin replacement
      of extensive, deep partial and full thickness burns. Covering burn defects with
      definitely engrafted, allogenic dermis and cultivated epithelial autografts (CEA)
      permits the subsequent withdrawal of cyclosporin A medication. Light-microscopy
      examination of biopsies, taken 12 and 24 months postgrafting, and electron
      microscopy of biopsies taken 12 months postgrafting, demonstrates a re
      established, but somewhat reduced anchoring of the CEA as compared with a normal
      epidermal-dermal junction. Clinical inspection, 20 months postgrafting, confirms
      the histological observations that epifascial transplantation is qualitatively
      inferior to placing the allogenic STSG on the subcutaneous tissue. In the first
      situation, the dermis is inelastic and collagen deposition is excessive, whereas
      in the second case collagen deposition is comparatively reduced and the dermis
      shows clinically some elasticity.

PMID- 8148071
TI  - Cultured autologous keratinocytes in fibrin glue suspension, exclusively and
      combined with STS-allograft (preliminary clinical and histological report of a
      new technique).
AB  - The use of cultured epidermal cell sheets has become a recognized method for the
      coverage of extensive burns. The disadvantages are a long time-lag until the
      cells are available, the fragility and difficult handling of the grafts, an
      unpredictable 'take' and extremely high costs. In three patients with deep
      partial and full skin thickness burns we have applied cultured autologous
      keratinocytes suspended in fibrin glue. In two of these patients the keratinocyte
      culture in the fibrin matrix (KFGS) was overgrafted with allogeneic, glycerine
      preserved split thickness cadaver skin. The area thus covered ranged from 3 to 15
      per cent TBSA. Cultured grafts were available between 2.5 and 3 weeks. The non
      confluent cells developed a continuous epithelial layer within the 4 days until
      the first dressing change. Histological examination showed a stratified
      neoepidermis. Clinically the new skin had satisfactory stability and mechanical
      quality. The epidermis of the allogeneic overgrafts desquamated within a few days
      without signs of inflammation, but there are indications that the STS-allograft
      dermis is at least partly integrated into the new skin and may serve as a
      scaffold for the grafted cell culture. The fibrin glue matrix seems to give
      sufficient adherence stability to keratinocytes that are grafted in an actively
      proliferating state. Further advantages are the easy repetition and application,
      as well as a reduction in operating time and costs in these severely injured
      patients.

PMID- 8148072
TI  - A mixture of allogeneic and autologous microskin grafting of rabbit skin wounds
      with Biobrane overlay.
AB  - A mixture of allogeneic and autologous microskin grafts (10:1 expansion ratio)
      were transplanted and overlain with Biobrane, on to full-thickness skin wounds
      (8.0 x 5.0 cm in size) in 16 rabbits. They were divided into two groups: in group
      I, the expansion ratio of both allo- and autograft was 20:1; in group II, the
      expansion ratio of allo- and autograft was 15:1 and 30:1 respectively. On day 9,
      all wounds of group I and II were almost completely resurfaced with
      neoepithelium. There was no serious rejection reaction within the neoepithelium
      and the wounds were maintained completely resurfaced after day 9. There were
      scales on the epithelialized wound which were more numerous in group II than in
      group I. Histological examination revealed that these wounds were resurfaced with
      well-differentiated epithelium which contained two different histological
      patterns. They were identified as the survived transplanted allogeneic and
      autologous microskin grafts, each having their own characteristic histological
      features and different sex chromosome. Thus both the largely expanded allogeneic
      and autologous microskin grafts could proliferate together and contribute to the
      resurfacing of the wound. With this method, the rabbit skin wound could be
      resurfaced completely after the ninth postoperative day with markedly minimized
      amounts of autologous and allogeneic grafts.

PMID- 8148073
TI  - Effects of washing with a neutralizing agent on alkaline skin injuries in an
      experimental model.
AB  - In this report a skin alkaline injury model was constructed using experimental
      rats and 2 N NaOH. We observed the effects of washing with a neutralizing agent
      on the subcutaneous tissue pH at 1, 10 and 30 min after injury and compared it
      with water-washing groups. In comparison with the water washing group, the peak
      pH values following the use of the neutralizing agent were significantly higher
      in the 1-min washing group, and significantly lower in the 10-min and 30-min
      washing groups. Changes in the pH values of the subcutaneous tissue after
      reaching a peak showed a similar course in the 1-min washing group, whereas in
      the 10 and 30 min washing groups there was a significantly different rate of
      decrease of pH. These results indicate that although treatment with a
      neutralizing agent directly after injury causes harmful effects due to the
      neutralizing reaction with a highly concentrated alkali. Subsequently with
      prolonged washing there is an effective reduction of the high pH.

PMID- 8148074
TI  - The significance of changes in serum tumour necrosis factor (TNF) activity in
      severely burned patients.
AB  - In order to explore the pathogenesis of postburn internal organ injury (OI) and
      multiple organ failure (MOF), serum TNF activity was measured by biological assay
      in 24 severely burned patients. Parameters related to internal organ functions
      were simultaneously measured. The results showed an obvious increase in serum TNF
      activity accompanied by increased serum myocardial and hepatic enzymes, plasma
      lactate and aggregations of WBC in internal organ tissues. Serum protein levels
      decreased substantially. These changes were more marked in patients suffering
      from both OI and MOF. It is suggested that large amounts of TNF are produced
      postburn and might have an important role in the development of OI and MOF.

PMID- 8148075
TI  - Phenol burns and intoxications.
AB  - Phenol burns and intoxications are life-threatening injuries. Roughly 50 per cent
      of all reported cases have a fatal outcome. Only a small number of cases have
      been reported with high serum concentrations after phenol burns who survived. In
      our own experience a patient with 20.5 per cent total body surface area deep
      partial skin thickness phenol burns and serum concentrations of 17,400
      micrograms/litre survived after immediate and repeated treatment of the scalds
      with polyethylene glycol (PEG) and silver sulphadiazine. A literature review of
      experiences with phenol intoxications reveals the advantages of PEG application.
      Questions on the need for enforced diuresis and haemodialysis as well as the
      initial treatment procedures are discussed. Advantages of different solutions for
      local therapy are reported.

PMID- 8148076
TI  - Adjunctive hyperbaric oxygen therapy in the treatment of thermal burns: a review.
AB  - Hyperbaric oxygen therapy provided in specially designed pressure chambers is
      currently the treatment of choice for decompression sickness, arterial gas
      embolism, and serious carbon monoxide poisoning. It is an important adjunct in
      the treatment of gas gangrene, chronic osteomyelitis, radiation injury, and
      indolent wounds. The potential benefit in the treatment of thermal burns is not
      well appreciated. Hyperbaric oxygen therapy may significantly reduce morbidity,
      mortality, and cost of care. The application of this technology based on the
      demonstrated beneficial effects on the pathophysiology of the burn wound merits
      consideration in selected patients.

PMID- 8148077
TI  - Massive burns: a study of epidemiology and mortality.
AB  - This study describes the epidemiology and mortality of patients with burns
      involving over 30 per cent of the body surface who were hospitalized between 1
      January 1988 and 1 January 1990. During this period 302 patients were
      hospitalized (8.1 per cent of those treated); of these, 52 (16.7 per cent) had
      burns affecting more than 30 per cent of the total body surface. There were 38
      males and 14 females (mean age, 43 years). The mean burn extent was 55.3 per cent
      of the total body surface, and the most common cause was fire (75 per cent); 67.3
      per cent of accidents occurred at home. Patient mortality in our series was 30.7
      per cent with a mean survival of 10.3 days.

PMID- 8148078
TI  - A simple and compressive splint for palmar skin grafting in young children with
      burns.
AB  - A simple, compressive, and easily applied splint which is suitable even for
      fearful and uncooperative patients after skin grafting for paediatric deep palmar
      burns is described. The hand, including the wrist and the forearm, is inserted
      between the palmar and dorsal plates of the splint and thus compression and
      immobilization act to decrease flexion contracture and dysfunction of the digits.
      Compression can be easily controlled by the use of leather bands.

PMID- 8148079
TI  - Epidemiological data and costs of burn injuries in workers in Switzerland: an
      argument for immediate treatment in burn centres.
AB  - A complete statistical evaluation of epidemiological data and costs of burn
      injuries in 1984 with a follow-up for 5 years is presented, considering a
      collective of 1.77 million workers in Switzerland. The majority of burns are
      minor injuries; only about 5 per cent of the burn victims are admitted to a
      hospital, 0.2 per cent died. Burn injuries at work are rare, mainly owing to
      strict safety measures. Only one-fifth of the costs caused by burns are due to
      medical treatment. All other expenses result from continuation of payments of
      salaries and annuities. The treatment of the few severely burned patients in burn
      units produces effective costs which are higher than the tariff paid by the
      insurance. Even so, the predominant portion of the enormous costs is taken up by
      wages while off work and annuities. As our conclusion we stress the importance of
      primary care for all severe burns including all burns of the hands in a
      specialized centre. Any economic effort for primary burn treatment, however high
      it may be, is justified if the duration of rehabilitation and invalidity can be
      reduced.

PMID- 8148080
TI  - The effect of early surgical intervention on mortality and cost-effectiveness in
      burn care, 1978-91.
AB  - A 14-year (1978-91) single centre analysis was performed involving 3561 patients.
      Several variables thought to influence burn outcome were included in the
      analysis, as was length of stay, interval between surgical interventions on each
      patient, and cost of care. Mortality rate declined by over 2 per cent (from 9.8
      per cent during the first 7 years to 7.3 per cent in the second 7 years, P <
      0.001). Multiple regression showed that percentage burn, presence of inhalation
      injury, and age had a significant effect on mortality. These variables, as well
      as the DRG distribution, were statistically evenly distributed over the 14-year
      study. There was a statistically significant decrease in length of stay (23 days
      in 1979 to 14.2 days in 1990), which significantly correlated with a decrease in
      interval between surgical interventions (14.76 days in 1979 to 6.12 days in
      1990). The average annual increase of hospital charges for burn care grew at 9.6
      per cent annually, higher than the consumer price index during the same time (5.8
      per cent) but substantially lower than the hospital market as a whole (10.8 per
      cent). Mortality rate of major burns has decreased significantly in this study,
      while burn severity indices remained constant. Increase in cost of care was
      substantially lower than that of general hospital care. This apparent cost
      efficiency is driven by a decreased length of stay closely correlated with
      aggressive surgical intervention for closure of the burn wound.

PMID- 8148081
TI  - Usefulness of narrow pedicled intercostal cutaneous perforator flap for coverage
      of the burned hand.
AB  - A narrow pedicled intercostal cutaneous perforator (np-ICP) flap is used for
      reconstruction of hand scar contractures after burns. This flap is designed with
      a narrow pedicle which includes some intercostal cutaneous perforators of 4-7th
      intercostal spaces, and with a wide distal area which lies over the costal cage
      and upper abdomen. Additionally the flap is thinned until only the subdermal
      vascular network is preserved in most of the wide distal area. It seems that this
      flap is more useful, not only functionally but also aesthetically, than
      conventional methods. This report describes the technique and concept, with a
      demonstration of some clinical examples.

PMID- 8148082
TI  - The dialysis debate: acute renal failure in burns patients.
AB  - Acute renal failure is an uncommon occurrence in burns patients, although the
      mortality of this condition remains high. We review briefly the literature on the
      incidence and management of acute renal failure in burns patients. We discuss the
      results of a questionnaire sent to all units in the UK examining this problem.
      Our findings suggest that acute renal failure is usually part of a complex
      multiorgan failure. However, an aggressive approach in the management of these
      patients can result in a significant improvement in prognosis, in the absence of
      a greater understanding of prevention of the condition. We have suggested
      measures that could be taken to aid the care of burns patients with renal
      failure.

PMID- 8148083
TI  - Domestic iron burns in children: a cause for concern?
AB  - The case notes of 26 children with contact thermal burns to the hand who were
      treated in the Burn Unit at Stroke Mandeville Hospital as inpatients during the
      period 1987-92 have been reviewed. The burns were found to be caused by a variety
      of injuring agents, although the domestic iron was the single commonest cause
      accounting for 46 per cent of cases. Mechanisms of iron injuries were variable
      although leaving a hot iron on the floor or on a low table were identified as
      being two important causes. Fifteen children (58 per cent) underwent either
      primary or tangential excision of the burn skin and grafting. The majority of the
      children had a satisfactory outcome, although five children (19 per cent)
      developed hypertrophic scars. The results of this study demonstrate the
      relatively high incidence of domestic iron burns as a causative factor for
      contact hand burns in children. Parental vigilance and leaving a hot iron in a
      secure place are two factors which will help to reduce the incidence of this
      potentially serious injury.

PMID- 8148084
TI  - A method of recording and objective assessment of hypertrophic burn scars.
AB  - A technique for recording the shape and size of hypertrophic burns scars during
      conservative treatment is described. This technique is extremely useful not only
      for an objective assessment of the healing process but also as an adjunctive
      research method for comparing two or more differing techniques of treatment.
      After taking a negative impression of the scar using dental impression material,
      a positive cast model of the scar is made, which is a three-dimensional copy of
      the scar. These cast models can be easily obtained and are very precise. They
      represent the height, size and general appearance of the scar, so that by taking
      positive impression models at regular intervals, and combining them with
      photographic and tonometric evaluations, they help in the evaluation of
      conservative treatment or in studying the mode of action of treatment.

PMID- 8148085
TI  - Surgeons', nurses' and bereaved families' attitudes toward dying in the burn
      centre.
AB  - Because death of a patient is one of the most emotionally disruptive events in
      the health professionals' life as well as the bereaved, it was hypothesized that
      surgeons' and nurses' attitudes in the burn centre would interfere with their
      emotional support of the bereaved family. Consequently, we performed a
      psychometric assessment of the surgeons', nurses' and bereaved families'
      attitudes about death and dying in the burn centre. A psychometric instrument was
      developed and validated that assessed 13 surgical directors' of burn centres, 13
      burn nurses' and nine bereaved family members' attitudes on death and dying in
      the burn centre. In the case of the bereaved family member, this instrument was
      complemented by interviews to ensure that the respondents understood each
      question. All surgeons and nurses were experienced health professionals working
      for an average of 12 +/- 8 years and 3 +/- 1 years respectively. The majority of
      burn surgeons (six) and the burn nurses (seven) found it to be emotionally
      difficult to support emotionally the bereaved family after the death of the
      patient. Over half the burn surgeons (seven) and nurses (seven) felt that the
      process of dealing with the bereaved family was different from that experienced
      in other hospital settings. The surgeons attributed this difference to the long
      duration of the patients' illnesses, while the nurses felt that it was due to the
      traumatic and painful qualities of burn injury. These emotional difficulties
      experienced by the staff in dealing with the dying patients were associated with
      a relatively low frequency of contact with the bereaved families after the
      patients' death.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148086
TI  - Clinical burn wound infection caused by L-forms of Staphylococcus aureus.
AB  - A patient with an infection with the L-form of Staphylococcus aureus occurring in
      burn wounds is reported. The authors conclude that the infection was attributable
      to a decrease in the host immunological functions and repeated administration of
      antibiotics resulting in the development of bacterial L-forms.

PMID- 8148087
TI  - Caecal perforation due to colonic ulcer in a burn patient.
AB  - Non-specific ulcers of the colon are occasionally reported as a cause of
      perforation of the colon. No previous cases have been reported in burn patients
      as a cause of perforation, although cases of haemorrhage have been cited. A 42
      year-old black-skinned female with a 26 per cent TBSA burn developed a caecal
      perforation from this cause. Treatment with caecostomy patient recovered
      successfully.

PMID- 8148088
TI  - An unusual cause of sunbed burns.
AB  - Three women successively using the same sunbed received superficial to medium
      partial thickness burns as a result of an ultraviolet filter slipping out of
      place. Whilst the longer-term effects of the various spectra of ultraviolet (UV)
      light continue to be evaluated, the near-immediate cutaneous and/or ocular
      sequelae of excess exposure are well known. Cutaneous burns are not, however,
      immediately manifest and it is concluded that suntanning devices should
      incorporate failsafe mechanisms activated by filter slippage or other
      malfunction.

PMID- 8148089
TI  - Unusual complication of nasogastric feeding.

PMID- 8148090
TI  - [Epidemiology of intestinal infection and operative rehydration strategy at the
      Mexican Institute of Social Security].
AB  - The purpose of the study was to analyze the trend of morbidity and mortality due
      to intestinal infections in children under the age of 1 (infants) and 1-4 years
      old (preschool children) among the population group covered by the Mexican Social
      Security Institute (IMSS) between 1983 and 1990. For this purpose, information
      was obtained from death certificates, outpatient consultation reports, and
      hospital discharges with a diagnosis of intestinal infections. Only direct
      beneficiaries of the IMSS were included in the study. Total and cause-specific
      mortality rates for infants and preschool children were calculated, as well as
      the incidence of intestinal infections in outpatient consultations and
      hospitalizations and case-fatality rates due to intestinal infections. During the
      study period, mortality rates among infant and preschool children decreased by
      15% and 20%, respectively. A reduction in intestinal infections accounts for
      73.2% of the decline in infant mortality and 62.6% of the decrease in mortality
      of preschool children. Incidence and case-fatality rates of intestinal infections
      also declined in both age groups. Lower morbidity and mortality rates may be due
      to the IMSS oral rehydration program and to the fact that most of the population
      group studied lives in cities and has received basic education. Notwithstanding,
      obstacles to further reducing the incidence of these diseases still exist.

PMID- 8148091
TI  - Repair of labial avulsion in a cat.
AB  - This photo essay illustrates a technique used for treating a cat presented with a
      trauma induced detachment of the labial mucosa. Stainless steel orthopedic wire
      was placed through the mandible to effect reattachment of the labial avulsion.

PMID- 8148092
TI  - Anatomy, diagnosis and management of disorders of the tongue.
AB  - The tongue is an integral and functional part of the oral cavity. This article
      reviews and describes various disorders of the tongue. A comprehensive
      description of diagnosis and management of tongue problems is included. A review
      of the anatomy related to the tongue is described.

PMID- 8148093
TI  - Masticatory muscle myositis.
AB  - This report examines a case of masticatory muscle myositis in a dog. Inflammatory
      disorders can affect the muscles of mastication. Two types of inflammatory
      myopathies have been described. The histopathology and immunochemical features of
      this case suggest an immune mediated basis for this disorder. The diagnosis and
      treatment are described for this immune mediated inflammatory myositis.

PMID- 8148094
TI  - Effects of preactivated MC540 in the treatment of lymphocytic plasmacytic
      stomatitis in feline leukemia virus and feline immunodeficiency virus positive
      cats.
AB  - Photoactive compounds and drugs are used therapeutically as antibacterial,
      antiviral and antitumor agents. This report examines the use of a photoactive
      compound, preactivated merocyanine 540 (pMC540), in the treatment of stomatitis
      in two cats that are both feline immunodeficiency virus (FIV) positive. One of
      the cats was also feline leukemia virus (FeLV) positive. Dramatic short term
      improvement is reported with the dosage regimen and complications.

PMID- 8148095
TI  - Dicalcium 1,4,5,8-naphthalenetetracarboxylate pentahydrate.
AB  - In the title structure, the 1,4,5,8-naphthalenetetra-carboxylate anion possesses
      2/m symmetry with the twofold axis coincident with the central C--C bond of the
      naphthalene rings. The ten atoms comprising the naphthalene core have a mean
      deviation of 0.033 A from the best least-squares plane describing these atoms,
      with the carboxyl C atom 0.395 (2) A removed from the plane. The dihedral angle
      between the carboxylate plane and the least-squares plane of the naphthalene
      rings is 46.2 (3) degrees. The O--C--O angle of the carboxylate group, 121.13(12)
      degrees, is smaller than normally expected, presumably due to the bidentate
      interaction with the Ca ion. The Ca ion is coordinated by eight O atoms: six
      carboxylate O atoms and two water O atoms. Because the Ca ion resides on a
      twofold axis there are only four independent Ca--O distances, which are in the
      range 2.368 (1)-2.681 (1)A. In this structure, the organic anions are separated
      by Ca ions and water molecules such that there are no short-range organic-organic
      interactions. One of the water molecules separating the organic anions is not
      involved in coordination with Ca, and is disordered.

PMID- 8148096
TI  - Structure of a modified nucleoside, 3' alpha-diethylphosphono-3' beta-hydroxy-5'
      O-tritylthymidine.
AB  - The modified nucleoside of the title was synthesized by nucleophilic addition of
      lithium diethyl phosphite to the corresponding 3'-keto nucleoside under basic
      conditions. C--P bond formation resulted from attack on the alpha face, trans to
      C(5') and the thymine ring. One molecule of EtOH crystallized with the nucleoside
      (C33H37N2O8P.-C2H6O). Intermolecular hydrogen bonds were observed between the O
      atom of the alcohol and the O(3')hydroxyl H atom, and between the phosphoryl O
      atom, O(5), and the N(3) H atom of the thymine ring.

PMID- 8148097
TI  - Crystal and molecular structures of pyridazinone cardiovascular agents.
AB  - The crystal and molecular structures of 11 6-substituted pyridazinone
      derivatives: 6-phenyl-3(2H)-pyridazinone-acetic acid (1/1) (1), 6-(4-aminophenyl)
      3(2H)-pyridazinone (2), 6-(4-aminophenyl)- 5-methyl-3(2H)-pyridazinone (3), 6-(4
      acetamidophenyl)- 3(2H)-pyridazinone (4), 6-(4-acetamido-2- methoxyphenyl)-3(2H)
      pyridazinone (5), 6-(2-aminophenyl)-3(2H)- pyridazinone (6), 6-phenyl-3(2H)-
      pyrazinone (7), 6-(4-aminophenyl)-4,5-dihydro- 3(2H)-pyridazinone (8), (R)-(-)
      6[4-(3-bromopropionamido)phenyl]- 4,5-dihydro-5-methyl-3(2H)-pyridazinone (9),
      (R)-(-)-6-(4-ammoniophenyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (-)-tartrate
      dichloromethane-methanol (1/1/1) (10), 4,5-dihydro-6-methyl-3(2H)-pyridazinone
      (11) have been determined as part of a study to determine the relationship
      between their cardiovascular properties and molecular structure and dimensions.
      For the two optically resolved chiral derivatives (9) and (10) the absolute
      configuration has been determined.

PMID- 8148098
TI  - Molecular and electronic structures of two (anticonvulsant) diphenylhydantoin
      derivatives.
AB  - 1-Benzyl-5,5-diphenyl-2,4-dioxo-3-imidazolidineacetic acid (AC), M(r) = 400.434,
      triclinic, P1, a = 8.7640 (3), b = 11.112 (1), c = 11.323 (2) A, alpha = 102.10
      (2), beta = 95.44 (5), gamma = 109.12 (1)., V = 1002.65 (30) A3, Z = 2, Dx = 1.33
      g cm-3, F(000) = 420, mu(Mo K alpha) = 0.852 cm-1, T = 293 K, R = 0.066 for 5551
      unique observed reflections. The compound crystallizes from ethanol at room
      temperature in the form of colourless prism. 3-(2,4-Dichlorobenzyl)-5,5-diphenyl
      2,4-dioxo-1-imidazolidineacetic++ + acid (AD), M(r) = 469.323, monoclinic, P2(1),
      a = 8.0399 (7), b = 9.7237 (6), c = 26.9768 (12) A, beta = 94.281 (4)., V =
      2102.92 (96) A3, Z = 4, Dx = 1.48 g cm-3, F(000) = 968, mu(Mo K alpha) = 3.417 cm
      1, T = 293 K, R = 0.066 for 5677 unique observed reflections. The compound
      crystallizes from ethanol at room temperature in the form of colourless prisms.
      Two approaches are employed in trying to understand the known differences in
      pharmacological activity: an analysis of the molecular geometries, and electronic
      structure calculations. A detailed analysis is made of the molecular geometries
      both from the X-ray diffraction results, and following energy minimization with
      molecular mechanics. The ab initio calculations employ the energy-minimized
      conformations. Several electronic properties are intercompared for AC, AD and
      their common parent molecule diphenylhydantoin (DPH). The analyses of geometry
      and electronic structure indicate dissimilarities between active and inactive
      compounds which may be linked to differences in the activity.

PMID- 8148099
TI  - The community integration questionnaire. A comparative examination.
AB  - The community integration questionnaire (CIQ) was designed to assess home
      integration, social integration and productive activity in persons with acquired
      brain injury. The instrument consists of 15 items and can be completed by self
      report or with the assistance of a family member or caregiver familiar with the
      person's health status and social activities. Previous research has demonstrated
      adequate test-retest reliability and internal consistency. This study was
      designed to examine further, the psychometric characteristics of the CIQ and
      begin the process of establishing the instrument's validity. The CIQ was
      administered to 341 persons with traumatic brain injury (TBI) and 210 persons
      without TBI or any other apparent disabilities. The results indicate that the
      total scores are normally distributed for both persons with and without TBI. A
      statistically significant difference (P < 0.01) was found between subjects with
      TBI and those without TBI for all three subscales of the CIQ and for total
      scores. Data analysis also revealed that the total CIQ scores statistically
      differentiated among subjects with TBI living in three different settings: (1)
      living independently; (2) living in a supported community situation and (3)
      living in an institution. Intercorrelations among the three subscales (home,
      social and productivity) demonstrated that the CIQ provides unique information in
      the assessment of community integration for persons with TBI. Areas of future
      research necessary to expand the research and program evaluation usefulness of
      the CIQ are identified.

PMID- 8148100
TI  - A profile of fibromyalgia in occupational environments.
AB  - The effect of the occupational environment on fibromyalgic patients has not been
      well studied. Individuals (321) from across the United States completed a
      questionnaire regarding effects of their current and past occupations on their
      fibromyalgia. Occupations with a high percentage of responders were general
      office workers (20%), health care providers (14%) and educators (11%). Of the
      respondents, 8% were unemployed. Activities reported to aggravate the symptoms of
      fibromyalgia were computer or typing (37%), prolonged sitting (37%), prolonged
      standing and walking (27%), stress (21%), heavy lifting and bending (19%) and
      repeated moving and lifting (18%). Activities that did not appear to exacerbate
      the symptoms of fibromyalgia included walking (19%), variable light sedentary
      work (15%), teaching (8%), light desk work (6%) and phone work (6%). Patients
      with fibromyalgia report that they do not tolerate prolonged, repetitive
      activities, maintaining any one position for sustained periods of time and jobs
      with high stress. Light sedentary occupations that allow varied tasks and
      changing positions appear to be tolerated the best.

PMID- 8148101
TI  - Further studies on the electrodiagnosis of diabetic peripheral polyneuropathy
      using discriminant function analysis.
AB  - Discriminant function analysis can be useful when applied to multiple nerve
      conduction parameters for diabetic and nondiabetic subjects to reveal the
      essential dimension along which key neuropathic differences occur between these
      groups. In this study, 19 electrophysiologic parameters were used in a stepwise
      discriminant function analysis to reveal a highly significant dimension of
      intergroup differences between 67 diabetic and 75 normal adult Japanese-American
      males. The classification functions thereby derived are more sensitive and
      specific than those reported previously for this population. Furthermore, when 72
      additional subjects with impaired glucose tolerance were examined, they showed
      considerable overlap with the normal and separation from the diabetic groups,
      respectively. Their intermediate position between normal and diabetics in the key
      discriminant dimension indicates that essential neuropathic change is, at most,
      incipient in this latter group.

PMID- 8148103
TI  - Who funds published research in physical medicine and rehabilitation. A
      commentary.

PMID- 8148102
TI  - Adventitious bursae in below knee amputees. Case reports and a review of the
      literature.
AB  - Adventitious bursae are known to occur from repeated friction and pressure but
      rarely have been reported in adult amputees. Four cases of adventitious bursae
      are described, which were noted during the course of a follow-up study of below
      knee amputees. Two bursae resolved with modification of the socket or
      refabrication. One developed bursitis and drainage and a fourth persisted in a
      patient with systemic lupus erythematosus.

PMID- 8148104
TI  - Workshop on pulmonary rehabilitation research. A commentary.

PMID- 8148105
TI  - Ethical considerations in the management of individuals with severe neuromuscular
      disorders.
AB  - There have been many recent advances in improving the quality of life and
      prolonging life for individuals with advanced neuromuscular disease. These
      include the use of physical medicine techniques to balance extremity muscle
      strength and improve range of motion and noninvasive techniques to provide
      inspiratory and expiratory muscle assistance to prolong life without resort to
      tracheostomy. Such advances help eliminate the "crisis" decision making about
      "going on a respirator" and sophisticated assistive equipment and robotic aids.
      Physicians and society in general use quality of life issues inappropriately
      derived by questioning physically able individuals to justify withholding or
      implementing life-sustaining therapeutic interventions for these individuals.
      Informed decisions about ethically and financially complex matters such as long
      term ventilator use should be made by examining the life satisfaction of
      competent individuals who have already chosen these options. The great majority
      of severely disabled ventilator-assisted individuals with neuromuscular disease
      are satisfied with their lives despite the inability to achieve many of the
      "usual" goals associated with quality of life in the physically able population.
      Their principle life satisfaction derives from social relationships, the
      reorganization of goals and from their immediate environment. Although the
      Americans with Disabilities Act is seen as an important step to prevent
      discrimination against disabled individuals, it does little or nothing for the
      self-directed disabled individual who is not informed by his/her physicians
      regarding potentially vital therapeutic options nor does it help those who are
      warehoused in institutions because of lack of a national personal assistance
      services policy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148106
TI  - A message to Dr. Death from a physiatrist.

PMID- 8148107
TI  - Comparative effects of fluoxetine, amitriptyline and serotonin on functional
      motor recovery after sensorimotor cortex injury.
AB  - A recent investigation of the effects of the antidepressants desipramine and
      trazodone on behavioral recovery in brain-injured animals suggested that
      antidepressants, which act to increase noradrenergic activity in the brain, may
      facilitate the rate of recovery, whereas those that act to increase serotonergic
      (5-HT) activity may hinder recovery and reinstate deficits in recovered animals.
      The present study was designed to evaluate these findings further by assessing
      the effect of a single intraperitoneal injection of fluoxetine (a relatively pure
      5-HT reuptake blocker), amitriptyline (a mixed 5-HT and noradrenergic reuptake
      blocker with alpha 1-adrenergic receptor blocking activity) or a single
      intraventricular infusion of 5-HT on recovery of beam-walking ability in animals
      with a unilateral sensorimotor cortex injury. None of the drugs significantly
      affected the rate of recovery. Although fluoxetine was ineffective in reinstating
      the motor deficit in recovered animals, amitriptyline reinstated the deficit in a
      dose-dependent fashion. Infusion of 5-HT resulted in an extremely transient
      reinstatement of the deficit, which was largely attributable to its short-term
      sedative properties. These results suggest that 5-HT may be less involved in
      functional recovery than previously thought. They also add further support to
      previous findings that indicate that drugs which act to antagonize alpha 1
      adrenergic activity (e.g., phenoxybenzamine) may interfere with motor recovery
      after sensorimotor cortex injury. An appreciation of the potential impact of
      certain antidepressants on functional recovery in brain-injured patients appears
      warranted.

PMID- 8148108
TI  - The value of routine chest roentgenograms on admission for rehabilitation after
      traumatic spinal cord injury.
AB  - The value of routine chest roentgenograms has come under increasing scrutiny in
      the medical literature. In this retrospective study we investigated the value of
      routine chest radiographs obtained on admission to a rehabilitation unit after an
      acute spinal cord injury. The charts of all patients admitted for rehabilitation
      after a traumatic spinal cord injury during a 1-year period were reviewed and 79
      patients fulfilled criteria for inclusion into the study. Of the 79 patients, 12
      had findings on routine admission films, 9 of which were felt to be significant
      (11.4%). All 9 patients with abnormal admission films had experienced
      cardiopulmonary complications during their acute hospitalization (P < 0.001).
      Fourteen patients with normal chest roentgenograms on admission had repeat films
      performed during their rehabilitation stay, 4 of which were abnormal. All 4 had
      experienced cardiopulmonary complications during their acute hospitalizations (P
      < 0.01). Our findings would support the selective use of admission chest
      roentgenograms in spinal cord-injured patients with clinical indications or a
      history of cardiopulmonary complications during their acute care stay.

PMID- 8148109
TI  - Determining differences in post discharge outcomes among catastrophically and
      noncatastrophically sponsored outpatients with spinal cord injury.
AB  - This study tested differences in functional independence status, level of
      psychologic distress and extent of handicap experienced after discharge from
      inpatient rehabilitation among a group of 125 outpatients with spinal cord injury
      (SCI) sponsored by one of three types of rehabilitation insurance payors:
      catastrophic (Michigan Automobile No-Fault and Workers' Disability Compensation),
      Medicaid and third-party privates. Outcome measures included the functional
      independence measure, the brief symptom inventory and the Craig handicap
      assessment reporting technique. Insurance data was obtained via medical chart
      reviews and interviews that were conducted either face-to-face or by telephone,
      using the benefits coverage inventory. No differences in terms of post discharge
      functional independence across subjects sponsored by the three payors was found
      when controlling for neurologic status. However, SCI subjects sponsored by
      different payors reported receiving different amounts of benefits. Subjects also
      differed on the extent of psychologic distress experienced after discharge and
      the extent of their handicaps. SCI subjects sponsored by Medicaid reported
      receiving fewer benefits, being more distressed and experiencing greater handicap
      in comparison to others. Third-party privately sponsored subjects, conversely,
      experienced less handicap and distress than did the study's other subjects.

PMID- 8148110
TI  - Characteristics of the silent period after transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation (TMS) of human cortex during voluntary muscle
      contraction produces a transient period of inhibition (i.e., silent period, SP)
      in the electromyographic (EMG) activity. The duration of the SP in relation to
      the level of muscle force (10%, 50% and 100% of maximum voluntary contraction) as
      well as possible cumulative effects of sequential TMS on the SP were studied.
      Methodologic problems were encountered in defining the SP and thus the duration
      of both an absolute (complete EMG silence) and relative (return of uninterrupted
      EMG activity) SP was measured. In all subjects, shortening of the SP duration
      occurred in relation to an increase in force when the criterion for absolute SP
      was used. Conversely, the relative SP duration suggested a trend toward
      prolongation with increasing force of contraction. No cumulative effects of TMS
      were observed on the absolute SP duration, whereas two subjects showed a
      cumulative effect of TMS on the relative SP. We conclude that the effect of
      muscle force and sequential TMS on the SP duration is dependent on the methods
      used to measure the SP. It is therefore essential to agree on methodology before
      SP measurements are clinically useful.

PMID- 8148111
TI  - [Metasympathetic system and neuroendocrine elements of the human cecal appendix.
      Immunohistochemical study].
AB  - This study was carried out to demonstrate the neuroanatomical bases of pain in
      non inflamed appendices. Fifty human cecal appendices were examined by means of
      an immunohistochemical method utilizing antibodies for S100 protein, Neuron
      Specific Enolase, Chromogranin A and Serotonin. In all samples histological
      analysis did not demonstrate inflammatory alterations. The neuroendocrine pattern
      was investigated. Results show numerous nerve fibers and ganglions around the
      muscle layers and within the submucosa and the lamina propria. Large
      neuroendocrine cell population shows immunohistochemical staining for
      chromogranin and serotonin. Neurogenous hyperplasia and the high density of
      epithelial neuroendocrine cells in non inflamed appendices suggest that neural
      mechanism and serotonin release from neurosecretory cells are implicated in
      appendical pain. The nerve hyperplasia might be the effect of serotonin release.

PMID- 8148112
TI  - Some anatomical remarks on the posterior region of the tympanic cavity.
AB  - The Authors have studied the posterior region of the tympanic cavity in 25 fresh
      human temporal bones, making horizontal and vertical sections. In all cases the
      Sinus Tympani has been observed and the same for the Sappey's Suprapyramidal
      Recess, near the Facial Sinus. It has been determined the distance between Sulcus
      Tympani and the facial canal which is very variable and this assumes great
      importance from a surgical point of view.

PMID- 8148113
TI  - Thermodynamical aspects of the polymerization reaction of PMMA cement mixed with
      phosphatic mineral phases.
AB  - The main problem related to the use of polymeric cement in orthopaedics is the
      high temperature reached during the polymerization, causing necrosis. This paper
      reports a thermodynamical study of the polymerization reaction of an acrylic
      cement mixed with powdered phosphatic phases. In particular, mixing of alpha
      tricalciumphosphate, beta-tricalciumphosphate and hydroxyapatite was proposed.
      Important preliminary results indicated that amounts of about 66% by weight of
      alpha-tricalciumphosphate reduced the polymerization temperature to about 58
      degrees C in respect to 100 degrees C of pure acrylic cement. In addition, a
      special chamber was designed and realized to monitor the temperature variations
      involved during the polymerization reaction of the different mixtures.

PMID- 8148114
TI  - [Computerized parametrization in orthognathodontics].
AB  - The relationship between unilateral posterior cross-bite and area and volumetric
      proportions of the palatal vault observed in the frontal plane were studied in 6
      cross-bite cases before and after the correction of the malocclusion by removable
      appliances. Comparison of area and volume were carried out between the
      hemipalatal vault with the teeth in cross-bite and the hemipalatal vault with the
      teeth in good occlusion. The results demonstrated discrepancies of measurements
      between the two hemipalatal vaults before treatment. After the correction of
      cross-bite few or no asymmetries were recorded.

PMID- 8148115
TI  - [Electroencephalographic effects of a new triazolobenzodiazepine (Adinazolam) in
      the rabbit].
AB  - In this study we investigated the central effects of adinazolam, a
      triazolobenzodiazepine, by means of neurophysiological techniques
      (electroencephalogram, EEG, and quantified analysis of EEG, QEEG). The drug has
      been administered at the doses of 0.1-1-10 mg/kg i.v. The evaluation of the data
      obtained by QEEG has demonstrated that this substance acts on the central nervous
      system. Particularly we observed that the drug at the middle and high doses
      caused an increase of the "slow waves sleep" EEG pattern. This preclinical study
      has shown that adinazolam possesses a neuropharmacological profile similar to
      that of atypical antidepressive and/or anxiolytic drugs.

PMID- 8148116
TI  - [Role of the dopaminergic system in experimental models of epilepsy].
AB  - It has been shown that neuroleptics which interact selectively with either D-1 or
      D-2 dopamine receptors possess a marked difference in their propensity on
      seizures. The aim of this work was to investigate whether the D-1 antagonist SCH
      23390 differs from haloperidol (D-2 antagonist) in models of experimental
      epilepsy induced by electrical stimulation of selected brain regions (hippocampus
      and amygdala), in rabbits. Haloperidol increased and SCH 23390 significantly
      decreased the susceptibility to seizures in both models investigated. The data
      suggest that the D-1 and D-2 receptor subtypes have different roles in the
      mechanisms underlying seizures.

PMID- 8148117
TI  - [Expression of HLA-DR, DP, DQ antigens in fibrous sino-nasal polyps].
AB  - In the last years nasal polyps have been studied by several authors with
      different methodologies; however, their etiology is still unclear. In this paper
      we have analyzed in four nasal polyps of fibrous type, the HLA class II (HLA-DR,
      DP, DQ) molecule expression by means of immunohistochemical techniques
      (immunoperoxidase and immunophosphatase). A strong inflammatory cell
      infiltration, a percentage increase of both HLA-DR+ and HLA-DQ+ cells (normal
      nasal mucous membrane stroma infiltrating cells: DR+ < 40%, DP+ < 2%, DQ+ < 3%;
      fibrous polyps infiltrating cells: DR+ = 68%, DP+ < 2, DQ+ = 7%) as well as a
      clear positivity for DR expression of both surface and glandular epithelia were
      observed in all polyps. Furthermore, in the stalk area of one of the studied
      polyps DR+DQ+ cells with macrophagic features and having tight. connections with
      the vessels were observed. The scanty vascularization with the presence of
      activated mononuclear and mast cells might be responsible for polyp growth by
      locally producing an anomalous concentration of growth factors.

PMID- 8148118
TI  - [Muco-ciliary transport in chronic inflammatory pathology of the middle ear].
AB  - The Authors have studied the behaviour of nasal mucociliary transport (MCT) in
      the chronic phlogistic pathology of the middle ear, in subjects suffering from
      simple and cholesteatomatous otitis. In both groups the duration of MCT was
      longer than a control group of normal subjects; instead no significant difference
      was observed either between the two kind of pathologies nor between the two
      different phases of the otitis (quiescence and breakthrough). The Authors
      conclude therefore that, in the recurrent phlogistic pathology of the middle ear,
      the function of MCT must be carefully studied, possibly corrected if damaged, to
      prevent the evolution in the breakthrough.

PMID- 8148119
TI  - [Bio-imaging for the study of organic changes in the C.N.S.: comparison between
      computerized tomography and magnetic resonance].
AB  - Several comparative studies have been carried out in order to evaluate the
      possible diagnostic superiority of Computed Tomography (C.T.) vs. Magnetic
      Resonance Imaging (M.R.I.) in different diseases of the Central Nervous System.
      The present investigation is aimed at critically revising this problem also
      including the study of patients clinical data as a criterion of choice. A sample
      of 69 subjects was examined. It was seen that in demyelinative as well as in
      chronic cerebrovascular diseases M.R.I. should be preferred because of its higher
      sensitivity and specificity. Concerning specifically chronic cerebrovascular
      diseases, clinical data can have a more significant role in justifying the choice
      of M.R.I. C.T., and M.R.I. should be considered as complementary rather than
      competitive in studying cerebral tumors and spinal cord pathology; the planning
      of surgical operations, needing a complete evaluation of data, which in these
      cases are very variable, requires the use of both methods.

PMID- 8148120
TI  - Chemistry and structure of a new canal sealer showing a dynamical behaviour.
AB  - The complete apical seal without percolation and transit of bacteria and their
      products along the wall of the endodontic canal is the fundamental condition to
      obtain a lasting result of a correct endodontic therapy. The aim of this study
      was to characterize a new formulation cement (PROENDO, VEBAS, Italy) with
      characteristics totally different from the conventional ones. Finally, we can
      assert that an alloplastic material like PROENDO, which is the subject of this
      study, bio-compatible, osteo-inductive, non-toxic, with adhesive capacities, is
      able to quicken the phenomena of restoration and recovery after an endodontic
      operation.

PMID- 8148121
TI  - Effect of strategy and attribution training on strategy maintenance and transfer.
AB  - Effects of rehearsal strategy and attribution training on strategy use and
      transfer were investigated with 12-year-old students who had mild or moderate
      mental retardation. Students were randomly assigned to four groups that received
      either rehearsal strategy training, attribution training, combined rehearsal and
      attribution training, or no training. Both rehearsal strategy groups outperformed
      the others at maintenance. However, at transfer, only the combined strategy and
      attribution group performed better than the attribution and control groups. For
      students with mental retardation, strategy transfer was enhanced by the addition
      of attributional training.

PMID- 8148122
TI  - Autistic features, personality, and adaptive behavior in males with the fragile X
      syndrome and no autism.
AB  - Nine males with mental retardation due to fragile X syndrome were compared to 9
      males with mental retardation of other etiology. Subjects were compared on
      measures of personality, autistic features, and adaptive behavior. Results
      suggested that males with fragile X syndrome have a distinct psychological
      profile. In terms of DSM-III-R definitions, they had more autistic features, more
      schizoid features, and more schizotypal features. On measures of temperament,
      these males were more shy, more socially withdrawn, less energetic, and more
      emotional. The two groups did not differ with respect to adaptive behavior
      skills.

PMID- 8148123
TI  - Relations among maternal stress, cognitive development, and early intervention in
      middle- and low-SES infants with developmental disabilities.
AB  - Relations between maternal stress and the development of infants with handicaps
      was examined in 72 middle-SES and 72 low-SES families who attended a weekly early
      intervention program. Measures of maternal stress and development of infants were
      obtained 10 months apart. Regression analyses predicted 81% of variance in later
      developmental level with initial Bayley MA, initial Mental Development Index
      (MDI), SES, initial stress, early intervention participation, and SES x Initial
      Stress x Attendance interaction. Subsequent maternal stress was predicted (42%
      variance explained) by initial stress, attendance, initial MDI, number of
      intervention agencies and MDI x SES x Attendance. Results were interpreted in
      terms of a transactional model.

PMID- 8148124
TI  - Aberrant lateralization of brainstem auditory evoked responses by individuals
      with Down syndrome.
AB  - Brainstem auditory evoked response latencies were studied in 80 males (13 with
      Down syndrome, 23 with developmental disability due to other causes, and 44 with
      no disability). Latencies for waves P3 and P5 were shorter for the Down syndrome
      than for the other groups, though at P5, as compared to latencies for the
      nondisabled group, the difference was not significant. The pattern of left versus
      right ear responses in the Down syndrome group differed from those of the other
      groups. This finding was related to research noting decreased lateralization of
      and decreased ability at receptive and expressive language among people with Down
      syndrome. Some individuals required sedation. A lateralized effect of sedation
      was noted.

PMID- 8148125
TI  - Long-term morbidity and management strategies of tracheal aspiration in adults
      with severe developmental disabilities.
AB  - The feeding skills and health of 73 adults with severe developmental disabilities
      who aspirated were examined between 1986 and 1990. Sixty individuals had profound
      mental retardation (82%) and 48, cerebral palsy (66%). Modified barium swallow
      studies, esophagrams and gastric follow-throughs were completed on 67 clients
      (92%). Twenty adults aspirated barium. Aspiration was specific for barium texture
      in 8 (40%). Mobility, level of mental retardation, or feeding skills did not
      discriminate those who aspirated. Mealtime respiratory distress (65%) or chronic
      lung disease (55%), however, were significantly associated with aspiration. More
      studies are needed on the early identification and management of aspiration.

PMID- 8148126
TI  - Object mastery motivation of children with Down syndrome.
AB  - Mastery motivation of children with Down syndrome and MA-matched typically
      developing children was examined. The two groups performed similarly with respect
      to the quality of their play but differed in level of task engagement and
      causality pleasure. The children with Down syndrome appeared to be less engaged
      in the task than were the typically developing group as indicated by shorter
      sequences of goal-directed behavior and higher rates of toy rejection. In
      addition, the children with Down syndrome displayed less causality pleasure with
      object exploration than did the typically developing children.

PMID- 8148127
TI  - Cardiovascular risk factor levels in adults with mental retardation.
AB  - Cardiovascular risk factors in a population of adults with mental retardation
      were examined. The subjects resided in three types of settings (16+ bed facility,
      group home, and natural family) and were measured on the following parameters:
      blood lipids, obesity, and smoking. The data were compared to a nonretarded
      population and to the guidelines established by the National Cholesterol
      Education Program. Results indicated that adults with mental retardation had
      cardiovascular risk profiles similar to those of individuals without mental
      retardation in the Framingham Offspring Study and that to the extent that
      cardiovascular health is a concern to the general population, it must also be a
      concern for individuals with mental retardation.

PMID- 8148128
TI  - Professionals' prognoses for individuals with mental retardation: search for
      consensus within interdisciplinary settings.
AB  - Previous studies have shown a lack of consensus in professionals' prognoses for
      individuals with mental retardation. The present study was designed to continue
      the investigation of professionals' prognoses for the achieved capabilities and
      residential and vocational placement of individuals with mild, moderate, or
      severe mental retardation. Four professional groups (N = 567 subjects) from 50 of
      the 52 University Affiliated Programs throughout the country were surveyed. The
      Prognostic Beliefs Scale was used. Results showed that physicians had
      significantly lower expectations and more pessimistic prognoses for children with
      moderate or severe mental retardation than did the other professionals. The only
      consensus on prognosis was for children with mild mental retardation. Results
      call into question one of the assumed benefits of interdisciplinary teams-
      communication--and its impact on professionals' expectations and prognoses for
      individuals with mental retardation.

PMID- 8148130
TI  - Temporomandibular joint synovial fluid effect on resorption of mouse calvarial
      bone in vitro.

PMID- 8148129
TI  - Peer-directed communicative interactions of augmented language learners with
      mental retardation.
AB  - Naturally occurring peer-directed communicative interactions of 13 youth with
      mental retardation and little or no functional speech who used the System for
      Augmenting Language (SAL) as their primary means of communication were described.
      Findings suggest that this system was an integral component of both successful
      and effective conversations and may be one important means of enhancing social
      interactions with peer communicative partners who have and do not have mental
      retardation.

PMID- 8148131
TI  - A cephalometric hard tissue assessment of maxillary and mandibular relationships
      in complete unilateral cleft lip and palate patients requiring orthognathic
      surgery.

PMID- 8148132
TI  - Flurbiprofen effects on bone resorption.

PMID- 8148133
TI  - Digital subtraction radiography for assessing alveolar bone grafts: diagnostic
      accuracy and sensitivity.

PMID- 8148134
TI  - The effect of elevated calcium on bone cells and neuronal cells.

PMID- 8148135
TI  - Effects of high calcium on bone metabolism.

PMID- 8148136
TI  - Effects of high concentrations of flurbiprofen on bone remodeling in neonatal
      mouse calvaria.

PMID- 8148137
TI  - An anatomical study of retinal arteriovenous crossings and their role in the
      pathogenesis of retinal branch vein occlusions.
AB  - To elucidate the anatomical features which predispose artery over vein (AV)
      crossings to be the preferential sites for retinal branch vein occlusions (RBVO),
      11 AV and six vein over artery (VA) crossings in 12 eyes from non-hypertensive
      donors who were aged 35 to 82 years, were studied by light and electron
      microscopy. At AV crossings the veins were often observed to abruptly alter
      direction to pass under the artery. Here focal stratification of the vein
      basement membrane opposite the point of contact with the artery was seen. A focal
      reduction in the vein lumen occurred at three of 11 AV crossings. In contrast,
      deviation of the vein, focal basement membrane stratification or focal narrowing
      was not seen at VA crossings. Both types of crossings had a common adventitial
      sheath when each vessel was of large calibre. This study demonstrated anatomical
      features which predispose AV crossings to be the preferential site for venous
      occlusion.

PMID- 8148138
TI  - An improved method of densitometry of red-free retinal nerve fibre layer
      photographs.
AB  - The red-free negatives of 53 right eyes (30 normal eyes and 23 glaucomatous eyes)
      and 51 left eyes (32 normal eyes and 19 glaucomatous eyes) were analysed using
      two different image densitometry techniques. The first technique measured the
      density from rectangular sample areas, while the second measured density from
      sector-shaped sample areas which more closely follow the course of the nerve
      fibres in the retina. Indices which measured the deviation of the data from a
      clinically determined normal 'gold standard' were calculated, and were used to
      determine the optimum sensitivity and specificity in separating normal from
      glaucomatous eyes. There is a significant difference between the data from the
      normal and glaucomatous groups of eyes, when measured from the sector sample
      areas. The relative efficacy of this technique is also shown by the improved
      values of sensitivity (from 42%-70% to 70%-91%), although specificity remained
      fairly constant (from 66%-83% to 62%-88%).

PMID- 8148139
TI  - Endophthalmitis in Auckland 1983-1991.
AB  - A review was made of 58 cases of suspected endophthalmitis presenting to Auckland
      Public Hospital between January 1983 and July 1991 (103 months). Thirty culture
      positive cases were found comprising 13 early onset postoperative, six delayed
      onset postoperative, five bleb-associated, four post-traumatic and two endogenous
      cases. The most frequent organism grown in postoperative endophthalmitis was
      Staphylococcus epidermidis. No conclusion could be reached as to the
      effectiveness of early versus delayed vitrectomy. Endophthalmitis due to S.
      epidermidis usually had a good prognosis while streptococcal endophthalmitis had
      a poor prognosis. Delayed-onset postoperative endophthalmitis most often had a
      good prognosis while bleb-associated endophthalmitis had a uniformly poor visual
      outcome. Two isolates responsible for cases of delayed-onset postoperative
      endophthalmitis, Propionibacterium acnes and Rhodococcus species, did not grow on
      agar plates until the seventh day of culture. Significant bacterial resistance to
      cephazolin was identified with 33% of Gram-positive and 75% of Gram-negative
      isolates resistant. Prevention of postoperative endophthalmitis is discussed.

PMID- 8148140
TI  - Acanthamoeba keratitis. A masquerade of presentation in six cases.
AB  - Acanthamoeba keratitis is an uncommon but devastating complication of contact
      lens wear causing significant ocular morbidity. Six consecutive cases occurring
      in Western Australia in an 18-month period are reported. In all cases either poor
      contact lens hygiene or an association with swimming pools and contact lens use
      is a feature. There is invariably a delay in making the diagnosis, with the
      appearance frequently mistaken for herpes simplex keratitis. In all cases corneal
      biopsy was required to confirm the diagnosis. Of the six patients, four responded
      to medical therapy alone, one required a corneal graft and one required
      enucleation. We suggest that earlier rather than later corneal biopsy is
      important in unresponsive cases of culture-negative keratitis, especially in
      contact lens wearers. We would agree that the treatment of choice is intensive
      topical propamidine and neosporin. Prevention by strict adherence to contact lens
      care and hygiene is urged.

PMID- 8148141
TI  - Phototherapeutic keratectomy for Reis Bucklers' corneal dystrophy.
AB  - Superficial keratectomy, penetrating and lamellar keratoplasty have all been
      advocated when intervention in Reis Bucklers' corneal dystrophy is necessary
      because of diminished visual acuity. In this study, 11 eyes were treated by
      phototherapeutic keratectomy with an excimer laser. Two eyes had previously been
      treated by penetrating keratoplasty. The visual acuity improved in all eyes, from
      an average of 6/60 to 6/9 with complete cessation of recurrent erosions. The
      technique was modified, with experience, to minimise the hyperopic shift that
      occurs with this procedure. Phototherapeutic keratectomy has significant
      advantages over other procedures and is now the procedure of choice once surgery
      is required in Reis Bucklers' dystrophy.

PMID- 8148142
TI  - Effective corneal retrieval in a general hospital. The Royal Melbourne Hospital
      Eye Bank.
AB  - An active program of corneal transplantation depends upon a constant supply of
      high quality donor tissue. We describe an effective and inexpensive system of
      corneal donor retrieval in a major teaching hospital, and present an analysis of
      its donor population. During the five-month period studied in detail (May to
      October 1991), 365 deaths occurred in the hospital. The relatives of the
      decreased were contacted and consent for donation was requested after 323 (88.5%)
      of these deaths. Consent was given in 212 cases (65.5% of requests), with a mean
      age of the donor population of 69 years. After screening donor tissue for
      quality, 110 pairs of corneal buttons and 10 globes of sclera were dispatched for
      surgery during the study period, giving an overall procurement rate of over 30%.
      Further, the efficient notification and 'on-call' retrieval system led to very
      rapid corneal retrieval, resulting in an average death to storage medium time of
      less than two hours.

PMID- 8148143
TI  - Reliability of the Otago photoscreener. A study of a thousand cases.
AB  - The Otago photoscreener is a 35 mm single len reflex camera in which the flash
      light comes from a narrow ring around the outer margin of its lens. The margin is
      also the limiting aperture of the optic system and in the centre of the lens is a
      flickering fixation light. In a colour photograph taken at a distance of 66 cm
      from the face of the subject who is accurately focusing on and fixing the camera
      fixation light with both eyes, the fundus reflex in each pupil is very dark red
      and the corneal light reflexes are symmetrical. If either or both eyes are not
      appropriately focused or fixing, the fundus reflex is brighter and yellow or
      white. This article describes a prospective trial of the performance of the Otago
      photoscreener in a series of 1000 infants with actual or suspected amblyopia,
      refractive error or strabismus. In this study photoscreening showed a sensitivity
      of 94% and a specificity of 79%. Photoscreening also identified some cases of
      esotropia and of refractive error which were missed on clinical examination. In
      this series photoscreening passed as normal three children with mild to
      moderately severe amblyopia. This represents les than 1% of the clinically
      abnormal children.

PMID- 8148144
TI  - The application of a computerised diagnostic index for ophthalmic practice.
AB  - All 2792 patients seen in my private practice between July 1989 and September
      1992 and receiving a diagnosis were coded according to the International
      Classification of Diseases-9 (Clinical Modification), 1979. Any procedures
      performed were coded according to the American Medical Association Current
      Procedural Terminology. Patient details and codes were filed by computer using a
      customised database in Foxpro 2.0 software. Those with minor refractive error or
      presbyopia alone and those who had no abnormality were excluded from the
      database. The set-up and maintenance of this diagnostic index is described and
      the database structure is specified. A modification of the glaucoma section of
      ICD-9, which better suited my needs, is presented. Examples of the potential
      information available from such a database is described, including some analysis
      of this general ophthalmic practice.

PMID- 8148145
TI  - Sturge-Weber syndrome and secondary glaucoma.

PMID- 8148146
TI  - Chronic canaliculitis.

PMID- 8148147
TI  - The distinction between multiple retinal pigment epithelial hamartomata (MRPEH)
      in familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal
      pigment epithelium (CHRPE)

PMID- 8148148
TI  - Polyhexamethylene biguanide in the treatment of Acanthamoeba keratitis.

PMID- 8148149
TI  - Primary tubulointerstitial nephritis and uveitis syndrome.

PMID- 8148150
TI  - Branch retinal arterial occlusion with trauma.

PMID- 8148151
TI  - Transplantation of the lateral rectus muscle to the medial side of the globe in
      third nerve palsy.

PMID- 8148152
TI  - Subconjunctival local anaesthesia.

PMID- 8148153
TI  - Demographic characteristics of ophthalmic outpatients at the Royal Victorian Eye
      and Ear Hospital.

PMID- 8148154
TI  - Developmental regulation of cytokine expression in the mouse brain.
AB  - Expression of four cytokine genes, transforming growth factor (TGF) beta 2, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and macrophage colony
      stimulating factor (CSF-1 also known as M-CSF) was examined to determine whether
      these genes are developmentally regulated in the brain. Northern blots were
      performed on RNA isolated from the mouse brain from embryonic day 15 (E15)
      through postnatal day 9. TGF beta 2 gene expression was relatively high in the
      earliest embryos studied and decreased after E16-E17, and the three transcripts
      were developmentally regulated. TNF-alpha and IL-6 were detected in total RNA on
      all days studied. CSF-1 was detected only in polyadenylated RNA. The data suggest
      that expression of these cytokines is related to specific developmental events
      that share cellular functions with regenerative or inflammatory processes.

PMID- 8148155
TI  - A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human
      umbilical vein endothelial cells and in placenta.
AB  - Placenta Growth Factor (PlGF) was recently discovered as a secreted growth factor
      for vascular endothelial cells and based on its homology to vascular endothelial
      growth factor (VEGF), can be classified as a new member of this growth factor
      family. We have carried out polymerase chain amplification (PCR) of RNA from
      human umbilical vein endothelial cells and placenta tissue and discovered a
      second species of PlGF, PlGF-2. PlGF-2 has a 21-amino acid insertion not present
      in PlGF-1 coding for a highly basic region near the C-terminus. This is similar
      to VEGF189. Northern analysis has shown, that the PlGF gene is expressed only in
      a limited number of cell types and tissues, e.g. human umbilical vein endothelial
      cells (HUVE) and placenta. Infection of Sf158 insect cells with recombinant
      baculoviruses specific for the two forms showed, that both, PlGF-1 and PlGF-2 are
      secreted efficiently into the supernatant and PlGF-2 can bind with high affinity
      to heparin. Both PlGF forms had a similar mitogenic potency for bovine aortic
      endothelial cells. Binding studies with 125I-VEGF165 demonstrate, that
      supernatant of PlGF expressing insect cells can compete for receptor binding.
      Similar to VEGF, PlGF can exist in different forms which are probably generated
      by differential splicing. The occurrence of two molecular forms of this
      endothelial specific growth factor suggests different physiological roles of the
      two forms during placental development and differentiation.

PMID- 8148156
TI  - Subcellular localization and biological activity of M(r) 18,000 basic fibroblast
      growth factor: site-directed mutagenesis of a putative nuclear translocation
      sequence.
AB  - Residues 27-31 (Lys-Asp-Pro-Lys-Arg) of the 155-amino acid form of basic
      fibroblast growth factor (bFGF) are in good agreement with a consensus sequence
      for nuclear translocation. To evaluate the role of this sequence in mediating the
      intracellular localization and biological activity of bFGF, basic residues Lys
      27, Lys-30, and Arg-31 were changed to neutral glutamine residues by site
      directed mutagenesis of the human bFGF cDNA. The bFGF mutant (M1Q-bFGF) was
      expressed in eukaryotic cells and in prokaryotic cells, from which it was
      purified to homogeneity. Transient expression of bFGF cDNA and of M1Q-bFGF cDNA
      in simian COS-1 cells followed by immunolocalization and by subcellular
      fractionation indicated that both molecules localize in the nucleus, as well as
      in the cytoplasm of transfected cells, and interact with nuclear chromatin and
      with eukaryote DNA in a similar manner. Prokaryotic expression of M1Q-bFGF cDNA
      yields a polypeptide endowed with a receptor-binding capacity and mitogenic
      activity similar to that exerted by wild-type bFGF. However, recombinant M1Q-bFGF
      showed a drastically reduced capacity to induce the production of urokinase-type
      plasminogen activator (uPA) in endothelial cells. The uPA-inducing activity of
      M1Q-bFGF was fully restored by the presence of soluble heparin in the culture
      medium. In conclusion, the sequence bFGF(27-31) does not appear to represent a
      nuclear translocation and/or retention sequence for bFGF. However, neutralization
      of its basic residues seems to modify the tertiary structure of the growth
      factor, thus affecting some of its biological properties.

PMID- 8148157
TI  - Immunohistochemical localization of basic fibroblast growth factor (bFGF) within
      growing and atretic mouse ovarian follicles.
AB  - Basic fibroblast growth factor is a biologically active peptide with a strong
      affinity for heparin. This growth factor has been previously shown to be
      mitogenic for a variety of mesoderm and neuroectoderm-derived cells. The
      immunohistochemical localization of basic FGF within mouse growing and atretic
      ovarian follicles is presented in the study. Ovarian tissue samples were obtained
      either (a) randomly from mice housed in a controlled light environment or (b)
      following the administration of exogenous gonadotropins to stimulate follicle
      development. Ovarian samples were fixed in Bouin's fluid for no longer than 18 h.
      Following fixation and paraffin embedding, sections were exposed to a primary
      antibody made in rabbits against either (a) human recombinant basic FGF or (b)
      the 1-24 synthetic fragment of bovine basic FGF. The primary antibody was
      followed by biotinylated goat anti-rabbit IgG and a biotin-avidin-peroxidase
      complex. There were no differences in the immunolocalization of basic FGF using
      either source of primary antibody or between randomly obtained ovarian samples
      and those obtained from mice given exogenous gonadotropins. Basic FGF was
      immunolocalized in follicle basal laminae and was also closely associated with
      individual follicle cells during all stages of ovarian follicle development.
      Basic FGF was absent in the theca interna, oocyte cytoplasm, zona pellucida and
      follicle fluid of normal growing follicles. Individual corpora luteal cells were
      surrounded by basic FGF but lacked cytoplasmic staining. Atretic follicles
      exhibited staining patterns similar to their respective stage of follicle
      development. However, when present, follicle fluid within atretic follicles was
      strongly positive for basic FGF. These results indicate that basic FGF may be an
      important factor involved in intraovarian control mechanisms.

PMID- 8148158
TI  - Leukemia inhibitory factor expression in human carotid plaques: possible
      mechanism for inhibition of large vessel endothelial regrowth.
AB  - One common feature of atherosclerotic plaques is the denudation of the
      endothelium covering the plaque and subsequent failure of endothelial regrowth in
      contrast to a marked proliferation of neocapillaries arising from the vasa
      vasorum within the medial wall. Previous studies in vitro have demonstrated the
      ability of leukemia inhibitory factor (LIF) to potently inhibit aortic
      endothelial cell growth while only slightly inhibiting the growth of adrenal
      cortex capillary endothelial cells. This selective effect of LIF on endothelial
      cells from different sources suggests that it may play a role in the failure of
      endothelial regrowth in atherosclerosis. Sections of human carotid endarterectomy
      samples were examined by in situ hybridization for LIF mRNA expression. In one
      third of the samples (4/12) examined, cells within the atherosclerotic plaque
      exhibited LIF expression. Immunohistochemistry of serial sections suggested that
      the LIF-positive cells were activated macrophages. These results suggest that LIF
      may play a role in the pathogenesis of atherosclerosis, particularly the
      denudation of the large vessel endothelium.

PMID- 8148159
TI  - Clonal analysis of erythropoietin stimulated J2E cells reveals asynchrony during
      terminal differentiation.
AB  - J2E erythroid cells proliferate and differentiate in response to erythropoietin
      (epo), the red blood cell specific hormone. Using methylcellulose colony assays
      and suspension cultures we have demonstrated that nearly all the cells stimulated
      by epo synthesized haemoglobin. To achieve maximum production of haemoglobin J2E
      cells had to be treated with epo for only 6 h; hormone added subsequently did not
      enhance haemoglobin synthesis. Although virtually all viable J2E cells produced
      haemoglobin, the cells matured morphologically at different rates. Thus, upon
      exposure to epo J2E cells become committed to erythroid terminal differentiation
      but proceed in an asynchronous manner.

PMID- 8148160
TI  - Erythropoietin induced ultrastructural alterations to J2E cells and loss of
      proliferative capacity with terminal differentiation.
AB  - Erythropoietin (epo) induced differentiation of the J2E erythroid cell line is
      characterized by haemoglobin synthesis, together with morphological changes and
      an immediate increase in proliferation. In this manuscript we have shown that the
      size of J2E cells decreased during differentiation and the nucleus to cytoplasm
      ratio was reduced appreciably. Furthermore, major ultrastructural alterations
      occurred-mitochondria, rough endoplasmic reticulum and Golgi apparatus decreased
      in size and number with maturation, while nuclei condensed considerably before
      extrusion. The use of mitotic indices, 3H-thymidine uptakes and flow cytometry
      confirmed that the immature J2E cells undergo enhanced replication shortly after
      epo stimulation. In addition, we demonstrated that cell division ceased as the
      cells entered the final stages of erythroid differentiation. Thus the J2E line
      provides a useful model, not only for haemoglobin synthesis, but for all aspects
      of erythroid terminal differentiation.

PMID- 8148162
TI  - 65th Annual meeting of the Genetics Society of Japan. Mishima, September 17-19,
      1993. Abstracts.

PMID- 8148161
TI  - Differential effects of PDGF isoforms on proliferation of normal rat kidney
      cells.
AB  - The effects of the PDGF isoforms AA, AB and BB have been studied on the
      proliferation of normal rat kidney cells, a non-tumorigenic fibroblast cell line
      which contains both type alpha and type beta PDGF receptors. On monolayer cells
      made quiescent by serum deprivation, PDGF-AA is a relatively poor mitogen
      compared to PDGF-AB and PDGF-BB. When these cells are made density-arrested
      following continuous incubation with epidermal growth factor, however, they can
      be restimulated to proliferate by all three PDGF isoforms with similar activity
      when added at sufficiently high concentration, resulting in phenotypic cellular
      transformation. Binding of radiolabelled isoforms to confluent NRK monolayers
      obeys the predictions of an induced receptor dimerisation model, and increases in
      the order AA < AB < BB. Upon preincubation of the cells with PDGF-AA, the dose
      response curve for mitogenic activity of PDGF-AB is shifted to higher
      concentrations, indicating that PDGF-AA can partly antagonize the growth
      stimulating activity of PDGF-AB, as has also been observed in ligand binding
      studies. This observation has subsequently been confirmed using fluorescence
      cytometric analysis. PDGF-AB is highly active in inducing anchorage-independent
      proliferation of NRK cells, but in all such assays PDGF-AA is at least as potent
      as PDGF-BB. Intriguingly, PDGF-BB is almost devoid of activity in inducing soft
      agar growth of these cells, in contrast to PDGF-AA. When compared to substrate
      attached cells, enhanced expression of the type alpha PDGF receptor was observed
      under anchorage-independent conditions. These results show that the relative
      potency of the three PDGF isoforms to stimulate proliferation of NRK cells is
      different for quiescent cells in monolayer, density-arrested cells and anchorage
      independent cells. Moreover it is shown that the biological activity of PDGFs can
      be impaired by the additional presence of other isoforms.

PMID- 8148163
TI  - [Indications and techniques of surgical intervention in chronic postembolic
      pulmonary hypertension].
AB  - The paper gives indications for surgical management and describes a surgical
      technique on the basis of the author's experience with 36 reconstructive
      interventions on pulmonary arteries in persistent post-embolic occlusion. The
      absolute indication for elimination of occlusion is central pulmonary arterial
      lesion which exists no more than 3 years and which is accompanied by elevated
      systolic pulmonary pressure (ranging from 51 to 100 mm Hg) and relatively
      preserved right ventricular myocardial function. The optimal surgical method is
      thrombin-thymectomy performed in deep hypothermia using intermittent
      extracorporeal perfusion.

PMID- 8148164
TI  - [Anatomic correction of transposition of the great arteries in infants:experience
      of the first 10 operations].
AB  - In the period March 1992 to January 1993, ten patients with transposition of
      great arteries (TGV) whose age ranged from 9 days to 8 months and body weight 3.2
      to 7.2 kg were operated on using the arterial switch. A single-stage anatomic
      correction was made in 2 patients with patent arterial duct, 4 with ventricular
      septal defect (VSD), one with multiple VSD. Three patients with common TGA
      underwent correction in 2 stages: arterial switch followed prior constriction of
      the pulmonary artery switch followed prior constriction of the pulmonary artery
      and subclavian-pulmonary anastomosis. In all cases of single VSD, it was closed
      with a flap made from the Gore-Tex material. In the whole series of operations, 2
      patients died: one being on the operating table due to anesthesiological errors,
      the other due to coronary blood flow disorder 3 hours after surgery. Six of the 8
      discharged patients were followed 3-8 months after surgery. Two patients needed
      digitalis. No sign of myocardial ischemia was detected in antibody. All the
      patients were found to have normal left ventricular pump function. These
      surgeries are the first in our country and so our little experience may be of
      interest for national specialists.

PMID- 8148165
TI  - [Attempt at allo-aortal conduits in the correction of congenital heart defects].
AB  - In the period September 1990 to April 1993, an allo-aortic conduit was used in 16
      patients during reconstruction of the right ventricular outflow duct. The
      patients age ranged from 2 years 8 months to 14 years, their body weight was 11.8
      to 26 kg. Seven patients were diagnosed as having pulmonary atresia with
      ventricular septal defect, 4 had Fallot's tetrad and 5 transposition of great
      vessels with pulmonary stenosis and ventricular septal defect. The allo-aortic
      conduit made by the procedure developed at the A. N. Bakulev Institute of
      Cardiovascular Surgery, Russian Academy of Medical Sciences, was used in all
      cases to reconstruct the right ventricular outflow duct. The allografts were
      sterilized in a solution containing culture medium RPMI-1640 and mixture of
      antibiotics. After sterilization, the prostheses were frozen in liquid nitrogen
      vapours and kept at -150 to -160 degrees C till their clinical application. In
      the immediate postoperative period, 2 patients died, which amounted to 13%. Two
      deaths were caused by excessive bleeding, but in one case the implanted conduit
      wall bled. The residual right ventricle-pulmonary artery gradient was no more
      than 23 +/- 17 mm Hg. A discharge echocardiographic examination of patients found
      no valvular dysfunction of the implanted conduits on days 12 to 26 days after
      surgery. The findings suggest that the allo-aortic conduits prepared at the A. N.
      Bakulev Institute of Cardiovascular Surgery, Russian Academy of Medical Sciences,
      can be regarded as the prostheses of choice in the surgery of congenital cardiac
      malformations.

PMID- 8148166
TI  - [Cryo-treated allo-prosthesis: applications and complications].
AB  - From January 1987 to December 1992, fifty two patients aged 1 day to 20 years
      were implanted cryo-treated homografts into the right-sided position. The
      patients were diagnosed as having severe Fallot's tetrads, common arterial trunk,
      transposition of great vessels, vascular bifurcation with pulmonary atresia and
      isolated pulmonary atresia. The authors implanted 56 homografts, out of them 37
      aortic and 19 pulmonary. In the early postoperative period 8 (15.4%) patients
      died whereas in the late period 1 (1.92%) patient. Out of complications,
      pseudoaneurysm, calcification with pseudoaneurysm, flap dilatation, and severe
      prosthesis calcification were found in 1, 1, 1, and 4 patients, respectively. The
      development of pseudoaneurysms is likely to result from incorrect treatment of
      donor tissue and to be not so infrequently as previously assumed. To prevent
      their development is to apply accessory individual sutures to the gaskets in the
      area of the anterior wall of proximal anastomosis and to use the Gore-Tex
      material for an external flap.

PMID- 8148167
TI  - [Immediate and late results of transluminal balloon angioplasty of Blalock
      Taussig stenosing anastomosis in cyanotic congenital heart defects].
AB  - Transluminal balloon angioplasty of Blalock-Taussig's stenotic anastomosis was
      performed in 37 patients with various congenital heart diseases in 1989 to April
      1993. The patients' age ranged from 3 to 16 years (mean 8.4 +/- 0.5 years).
      Arterial blood oxygen saturation varied from 38 to 74% (mean 62.4 +/- 1.5%).
      Hemoglobin amounted to 14 to 28.4 g% (mean 19.0 +/- 8.4 g%). Phonocardiography
      recorded no or low-amplitude systolic-diastolic anastomosis murmur in points IV-V
      in all patients. After balloon anastomosis dilatation, arterial blood oxygen
      saturation increased, on an average, from 62.4 +/- 1.5% to 81.2 +/- 1.2%.
      Anastomosis angiometry performed prior to and following balloon dilatation showed
      its significant dilatation (on an average, from 3.39 +/- 0.19 to 5.26 +/- 0.24
      mm). There was a distinct systolic-diastolic murmur of anastomosis on the PhCG.
      Post-balloon-dilatation complications occurred only in 3 cases: femoral
      thrombosis in 2 patients and pulmonary edema in 1. The late results were studied
      in 18 patients at months 2 to 40. None of them showed deterioration of clinical
      results after balloon dilatation. Eight patients were radically operated on. The
      best results were achieved in patients with discrete anastomosis stenoses and
      when balloons whose diameter corresponded to that of the subclavian artery and
      equal to 0.92-1.2 mm were used. A good effect following balloon angioplasty was
      observed in 24 (64.9%), satisfactory and poor results were found in 12 (32.4%)
      and 1 (2.7%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148168
TI  - [Recommendations for implanting cardiac pacemakers in bradycardia].
AB  - The paper gives recommendations for cardiologists and cardiac surgeons who are
      engaged in working out indications, choice of the type and mode of cardiac
      pacing. Based on the understanding of the great importance of nomenclature
      documents concerning the development of indications for pacemakers implantation,
      the Working Group of the Expert Committee, Ministry of Health of the Russian
      Federation and Russian Academy of Medical Sciences, for implantable
      antiarrhythmic devices and electrophysiology has developed recommendations on
      pacemaker implantation in acquired atrioventricular (AV) block, in AV-block after
      myocardial infarction, chronic bi- and tri-fascicular block, sinoatrial nodal
      dysfunction, hypersensitive carotid sinus syndrome, neurovascular syndromes, as
      well as in childhood bradyarrhythmias. In developing the recommendations, the
      authors have used their own 25-year experience in implanting pacemakers and the
      recommendations proposed by the Working Group of the American College of
      Cardiologists and the American Association of Cardiologists in 1984 and 1991 for
      implanting pacemakers in bradyarrhythmias. The proposed recommendations define
      indications and contraindications for implantation of up-to-date pacemaker models
      and determine the behaviour policy of a specialist in selecting patients with
      bradyarrhythmias for the optimal pacing mode, which suggests a compulsory
      certification of the centers engaged in implanting pacemakers in
      bradyarrhythmias.

PMID- 8148169
TI  - [Surgical treatment of paroxysmal cardiac arrhythmias with extracorporeal
      circulation and deep hypothermic protection].
AB  - The paper analyzes the results of surgical management of the Wolff-Parkinson
      White syndrome in 29 patients. Evidence is provided that it is not necessary to
      perform an intracardiac electrophysiological study in all patients in the
      preoperative period. A method for pacing mapping is proposed, which is advisable
      to be used in conduction block by the accessory pathway during an operation.
      Surgical policy is also discussed in the paper in relation to the site of
      accessory pathway. The paper provides the results of surgical management of
      cardiac fibrillation in patients with the Wolff-Parkinson-White syndrome in deep
      hypothermic protection.

PMID- 8148170
TI  - [Clinical applications of xenopericardial conduits in surgery of ascending aortic
      aneurysms].
AB  - At the Department of Acquired Cardiac Diseases (Head is Prof. G. I. Tsukerman),
      A. N. Bakulev Institute of Cardiovascular Surgery, 145 patients underwent
      operation for ascending aortic aneurysms, out of them the Bentalle-De Bono and
      the Cabrol operations were performed in 81 and 25 patients, respectively, the
      remaining 39 patients had palliative interventions. From February 1991 to April
      1993, the clinic performed in 11 patients prosthesis of the ascending aorta with
      a xeno-pericardial conduit containing a bioprosthesis of the same tissue. The
      paper describes the technical features of bio-conduit implantation. The use of
      xeno-pericardial conduits facilitates the technique of applying anastomoses,
      lowers hemophilia and reduces the length of an operation. Hemorrhagic and
      thromboembolic events are expected to be reduced in late periods. At the hospital
      stage 1 patient died. The cause of his death was peri-coronary hematoma. Ten
      patients are still under observation. Repeated examinations have not detected no
      specific complications typical of those observed in the application of synthetic
      conduits. The first experience has proved to be quite promising. However, the
      final assessment is possible only when sufficient clinical materials are
      accumulated and late outcomes are studied.

PMID- 8148171
TI  - [Prosthesis of the aortic valve by a loose allograft].
AB  - A procedure has been developed to prepare live aortic allografts, which consists
      in taking a valve early after a donor's death, sterilizing it in antibiotics and
      freezing it to -190 degrees C in the presence of the cryoprotective agent
      dimethylsulfoxide. The preservation of valve tissue is evidenced by morphological
      studies. The first 3 operations for aortic valvular diseases were performed. In
      two cases, the indication for surgery was infectious endocarditis refractory to
      antibiotic therapy. Postimplantation complications were not seen. The competence
      of the allograft was confirmed by intraoperative transesophageal
      echocardiographical study. The patients examined 4 months postoperation developed
      no signs of aortic incompetence and infectious endocarditis. Thus, the creation
      of a bank of live valves allows this prosthesis to be implanted with appropriate
      indications, one of which is active infectious endocarditis of the aortic valve.

PMID- 8148172
TI  - [Comparative assessment of variants of potassium crystalloid cardioplegia].
AB  - Sixty eight patients operated on for valvular abnormalities were examined. In
      Group 1 (n = 34) myocardial protection was made by potassium solutions containing
      different potassium concentrations: 30 mM and 5 mM for induction and reinfusion,
      respectively. In Group 2 (n = 34) a hyperosmolar oxygenized cardioplegic solution
      containing K+, 15 mM, and Mg2+, 16 mM was administered under the same conditions.
      In the early postoperative period, no differences were found in the frequency and
      size of inotropic support, as evidenced by central hemodynamic parameters. ECG
      showed that in Group 2 there was a reduction in the frequency of changes of S-T
      segment, indicating the presence of myocardial ischemic changes. A 24-hour Holter
      monitoring demonstrated that life-threatening ventricular arrhythmias occurred
      significantly more infrequently in Group 2. The ultrastructural study of
      intraoperative biopsy specimens of the myocardium, including their treatment with
      colloid lanthanum showed that the tracer had penetrated virtually into all
      cardiomyocytes at the peak of ischemia and reperfusion in Group 1. In Group 2,
      ultrastructural changes were less profound and the particles of the tracer
      lanthanum had penetrated into the sarcoplasm of 15% of cells. Inadequate
      myocardial protection cannot be regarded as a cause of one of three deaths from
      acute heart failure. The studies demonstrated that crystalloid potassium
      cardioplegia was highly effective. However, the possibility of additionally
      affecting the permeability of a cell membrane by changing the solution
      composition (elevating magnesium concentrations) and the reduction of frequency
      of cardiac arrhythmias suggest that each components of the cardioplegic solution
      should be studied.

PMID- 8148173
TI  - [Indications for repairing the internal carotid artery after carotid
      endarterectomy].
AB  - From 1983 to 1989, a total of 182 patients with atherosclerotic stenosis of the
      internal carotid artery (ICA) were examined and operated on. They underwent 198
      carotid endarterectomies (EAE). In the long-term postoperative period, Doppler
      sonography and spectral analysis of an ultra Doppler signal were used to study
      143 patients. Depending on the type of endarterectomy, 2 groups of patients were
      identified (1) 61 who had after EAE a plastic bifurcation operation with
      transition to the ostium of the ICA by means of a flap from a fragment of a
      synthetic prosthesis, autovein or xeno-pericardium; (2) 82 underwent EAE without
      dilatation of ICA. The analysis of the results of the studies revealed that after
      carotid EAE, the incidence of restenoses was 18.2%, that of thromboses was 8.4%,
      the incidence of atherosclerotic restenoses depended on the method to close the
      arteriotomic ostium: when the dilating flap was used, it was 1.5%, in isolated
      carotid EAE without its use, it was 11.03%. The incidence of myointimal
      restenoses in patients undergone plasty or no plasty of ICA was virtually equal.
      In atherosclerotic restenosis, 18.2% developed a negative dynamics of
      cerebrovascular insufficiency, whereas in thromboses 25% did, myointimal
      restenoses ran without clinical signs. The low incidence of atherosclerotic
      restenosis in plasty of carotid bifurcation made it the method of choice. Taking
      into account the nature of myointimal hyperplasia and the absence of clinical
      signs it should be noted that repeated reconstruction in this restenosis is not
      indicated, while in atherosclerotic restenosis, reconstruction is indicated in
      the presence of clinical manifestations.

PMID- 8148174
TI  - [Role of extra-intracarotid anastomosis in the surgical treatment of chronic
      cerebral ischemia].
AB  - About 500 patients with ischemic brain lesions were studied. Out of them 201
      patients underwent 230 operations: 140 extra-intracarotid bypass (EIB) and 90
      various interventions on brachiocephalic branches. The study of cerebral
      hemodynamics by examining blood pressure in the central artery of the retina and
      middle cerebral artery during surgery, comparison of these findings with those of
      Doppler sonography and angiography made the authors conclude that EIB improves
      cerebral hemodynamics, and in some cases it is the only intervention able to
      improve the status of patients. In severe disseminated atherosclerosis with
      occlusion of one of the carotid arteries, EIB should follow other interventions
      on brachiocephalic branches. EIB was found to make the natural history of
      cerebral failure steady in 80.3%.

PMID- 8148175
TI  - [Use of the superficial femoral vein in reconstructive-corrective vascular
      surgery].
AB  - The paper describes the procedure and results of using the femoral vein in
      reconstructive-corrective operations on arteries. The femoral vein was used in
      infection of a synthetic vascular prosthesis in the inguinal area in 24 patients,
      in the reconstruction of arteries below the inguinal ligament in the absence or
      in applicability of the large subcutaneous vein in 17 patients, in vascular
      plasty during a radical removal of malignant tumors in 5 patients. A good result
      was achieved in 83.4 +/- 7.6% in prosthesis infection, in 70.6% in plastic
      operations of the femoral-popliteal segment, and in all 5 cases in arterial
      plasty during removal of tumors of various sites. Pronounced phenomena of
      transient venous insufficiency were observed in 3 patients.

PMID- 8148176
TI  - [Reconstruction of the right ventricular outflow tract without using the
      traditional conduit].

PMID- 8148177
TI  - [New system for diagnosing acute circulatory disorders and assessing drug choice
      and dosage].
AB  - The assessment of the status of a patient and diagnosis are first made strictly
      algorithmically. At the same time the procedure is monitored by a physician in
      terms of his experience and knowledge. The dialogue is made on the basis of a
      model and images which reflect the pattern of blood circulation. The diagnosis is
      made by isolating the key pathophysiological link and interpreting it by means of
      a clinico-mathematical classification. The usual wording based on the evaluation
      of the severity and stage of a pathological process is supplemented with
      assessments of compensatory, protective, and other adaptive changes which greatly
      influence the choice of a therapy. The action of drugs is evaluated by their
      cumulative effects on the changes in physiological functions determining their
      properties, direction and magnitude of alterations of the weakest link. The
      clinical experience has shown that the procedure is beneficial for rapid
      detection of clinically significant changes, choice and assessment of
      therapeutical efforts just during an operation and in the early postoperative
      period.

PMID- 8148178
TI  - [Anatomic correction of transposition of the great vessels in a newborn].

PMID- 8148179
TI  - Nutritional management of infants with cystic fibrosis.

PMID- 8148180
TI  - Paediatrics in Hong Kong.

PMID- 8148181
TI  - Vaccines against invasive Haemophilus influenzae type b disease.

PMID- 8148182
TI  - Hospital admission rates for asthma and pneumonia in Fijian and Indian children.
AB  - To confirm the clinical impression that Melanesian Fijian and Fiji Indian
      children differ in their profiles of respiratory morbidity, national hospital
      admission statistics for respiratory diseases in children aged 5-14 years were
      examined for 4 years between 1985 and 1989. The mean annual admission rate for
      asthma was three-fold higher in Indians (1.68/1000) than Fijians (0.56/1000);
      rate ratio (Indian:Fijian) = 3.00, 95% confidence interval 2.54-3.55. Conversely,
      the mean annual admission rate for pneumonia was three-fold higher in Fijians
      (1.70/1000) than Indians (0.50/1000); rate ratio (Fijian:Indian) = 3.39 (2.85
      4.03). Admission rates for influenza, tuberculosis and bronchiectasis were also
      higher in Fijian children. Fijian and Indian children differ in hospital
      admission rates for respiratory diseases, possibly due to differences in
      incidence, prevalence or severity.

PMID- 8148183
TI  - Six year trend of neonatal septicaemia in a large Malaysian maternity hospital.
AB  - A study carried out in the Maternity Hospital, Kuala Lumpur over a 6 year period
      from 1986 to 1991, showed that the annual rates of septicaemia ranged from 5.2 to
      10.2/100 admissions. Septicaemia accounted for between 11.0 to 30.4% of all
      neonatal deaths. The case fatality ratios ranged from 23.0 to 52.2%, being
      highest in 1989 when basic facilities were compromised. Low birthweight neonates
      accounted for 55.5% of those with septicaemia. The most common causative
      organisms were Staphylococcus epidermidis and Staphylococcus aureus in 1986 and
      1987, but from 1988 Klebsiella species became the most common. More than 50% of
      neonatal septicaemia occurred after the age of 2 days. The results of the study
      demonstrated the dynamism of infection control: when control measures introduced
      earlier were not sustained, outbreaks of nosocomial infection recurred or
      worsened.

PMID- 8148184
TI  - Infant weaning practices in Adelaide: the results of a shopping complex survey.
AB  - The results are presented of a survey of infant weaning practices carried out in
      shopping complexes in the Adelaide metropolitan area. The types of foods and
      fluids currently being consumed by the sample of 258 healthy infants was
      documented, and a comparison made between the feeding practices of breast and
      artificially fed infants and with respect to socio-economic status. While the
      majority of weaning diets were compatible with the South Australian guidelines,
      40% of infants under 4 months of age were having solid foods and a greater
      percentage of these infants were artificially fed. Iron intake may not be optimal
      after six months of age with the increasing use of cow's milk and non-fortified
      adult cereals. There is an increasing awareness of the inappropriateness of
      adding sugar and salt to infant foods; however, foods high in sugar and salt are
      still being used. The results suggest that parents may not always be aware of or
      understand the rationale behind recommendations for weaning and that dietary
      guidelines for adults and children may not always be appropriate for infants.
      Consistent guidelines for infants, modified to consider current food trends,
      would be useful for parents.

PMID- 8148185
TI  - Reducing the lead load in childhood.

PMID- 8148186
TI  - Cotside plasma rather than whole blood estimates of blood glucose in the newborn.
AB  - An evaluation of the use of a glucose reflectance meter for the cotside
      measurement of plasma rather than whole blood glucose was undertaken. Three
      hundred and twelve samples were obtained for examination. There is a closer
      correlation between plasma glucose than whole blood glucose to laboratory values.
      Confidence and prediction intervals show that even separating plasma from whole
      blood at the cotside does not improve the reliability of glucose reflectance
      meters when predicting blood glucose values in the context of managing high risk
      newborn infants. The cotside measurement of blood glucose using glucose
      reflectance meters should be abandoned and improved methods for quickly obtaining
      accurate laboratory data should be instituted.

PMID- 8148187
TI  - Plasma fibronectin levels in extremely preterm infants in the first 8 weeks of
      life.
AB  - Fibronectin has in the past been considered to function simply as a non-specific
      plasma opsonin. However, recent studies have demonstrated that this molecule
      plays an important role in fundamental components of the immune response, for
      example, neutrophil adhesion, T cell activation and endothelial function.
      Additionally, fibronectin is important in lung homeostasis where it contributes
      to alveolar epithelial integrity. In this study plasma fibronectin levels were
      measured longitudinally in a group of extremely preterm infants, mean gestational
      age 27 weeks. Plasma fibronectin levels at birth were significantly lower in the
      preterm study group than in term controls (mean 91 +/- 33 micrograms/mL compared
      with 214 +/- 62 micrograms/mL in the term controls, P < 0.0001). The preterm
      cohort demonstrated a more than two-fold rise in plasma fibronectin on days one
      and two; levels fell almost to baseline values by day three with a subsequent
      slow rise to a plateau by day 28. No further increase was seen by day 56. This
      sequence of early changes in fibronectin levels mirrored closely the time course
      of respiratory distress syndrome. Infants of mothers with pre-eclampsia had
      significantly lower peak fibronectin levels than in those without (P = 0.016),
      and those infants with bronchopulmonary dysplasia showed a trend towards lower
      basal fibronectin levels (P = 0.07) and a greater difference between peak and
      basal levels (P = 0.05). Neonates, particularly those born preterm, have blunted
      immunological responses to infection. Fibronectin plays a key role in
      immunological responsiveness. The significant changes in fibronectin levels after
      birth in the preterm neonate are likely to have important pathophysiological
      consequences.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148188
TI  - C-reactive protein as a diagnostic tool of sepsis in very immature babies.
AB  - Three hundred and nine septic screens were performed on 123 consecutively
      admitted infants of < 30 weeks gestation. As part of the septic screen, serial
      quantitative measurements of C-reactive protein (CRP) were performed daily until
      discontinuation of antibiotic therapy. Complete blood counts were performed daily
      for the first 2 days of each septic episode. The babies had a mean birth weight
      of 1035.8 g s.d. 273.2 and a mean gestational age of 27 weeks s.d. 1.8. A CRP
      level of 10 mg/L or above was considered abnormal. Subsequently the receiver
      operator characteristic curve for CRP was constructed to demonstrate the ideal
      cut off value. Of the 309 septic screens, there were 51 instances of proven
      sepsis and 39 instances of deep culture negative sepsis. In the remaining 219, a
      diagnosis of proven or deep culture negative sepsis could not be made. On the
      first day of the septic episode CRP showed a sensitivity of 62.7%, specificity of
      87.2% and negative predictive value of 92.2% for proven sepsis. There was a
      significant increase in the sensitivity (90.2%) and negative predictive value
      (97.7%) of CRP with a specificity of 80.6 when both day 1 and 2 estimations were
      combined. We conclude that when the CRP is elevated on day 1 and/or day 2, the
      diagnosis of sepsis is extremely likely and when the CRP is within normal limits
      on days 1 and 2 of the septic episode, neonatal sepsis can be confidently
      excluded and antibiotic therapy ceased.

PMID- 8148189
TI  - Carbon dioxide concentrations in the environment of sleeping infants.
AB  - In 22 infants continuous measurements were made of the concentration of carbon
      dioxide (CO2) in inspired air during sleep. Evidence was found of CO2 enrichment
      of inspired air in certain environmental conditions. The levels achieved were not
      sufficiently high to acutely endanger an infant. Carbon dioxide concentrations as
      high as 2-3% were observed in the prone position when the infant's head was under
      a blanket and when the lower face was obscured by bedding. Sleeping prone on a
      sheepskin also resulted in an increased concentration of CO2 but to a lesser
      extent than being under a blanket. In awake infants the presence of a pacifier
      also promoted an excess of CO2 in the inspired air, both in the prone and supine
      positions. The physiological and clinical implications of these findings, in
      relation to the Sudden Infant Death Syndrome (SIDS), are unknown and warrant
      investigation.

PMID- 8148190
TI  - A review of venovenous haemofiltration in seriously ill infants.
AB  - Between April 1989 and October 1991, 13 severely ill infants, median age 13 days
      (range 1-180 days), median weight 3.5 kg (range 2.5-4.8 kg), received continuous
      venovenous haemofiltration (CVVH) for a median duration of 39 h (range 5-234 h).
      Filtration was performed through a double lumen catheter inserted into a central
      vein. The indications for filtration included acute renal failure (8), fluid
      overload (5), inborn errors of metabolism (3) and sepsis (1). Some infants had
      more than one indication. The median Paediatric Risk of Mortality (PRISM) score
      on the day of admission to the intensive care unit was 27 (range 8-42). No change
      in the level of respiratory support was required following the commencement of
      CVVH. Serum electrolyte concentrations and plasma osmolality remained normal
      throughout. Serum creatinine fell from a mean of 0.11 mmol/L (95% CI 0.058-0.168)
      to 0.07 mmol/L (CI 0.034-0.112). Urea fell from a mean of 9.5 mmol/L (CI 4.4
      14.6) to 6.5 mmol/L (CI 2.7-10.3). Platelet counts fell by 40-50% from a mean of
      126 x 10(6)/mm3 (CI 72-180) to 69 x 10(6)/mm3 (CI 36-103) 18 h following
      commencement of filtration but no bleeding was encountered. The main complication
      was a thrombosis of the superior and inferior vena cava in one infant. Four
      infants survived to be discharged from intensive care. Continuous venovenous
      haemofiltration, with its inherent advantages over arteriovenous haemofiltration,
      is feasible in small infants using standard paediatric equipment.

PMID- 8148191
TI  - Patterns of weight growth in aboriginal children on Queensland communities.
AB  - We have used data from existing health records to study the birthweights and
      percentage weights for age (%W/A) of children in five Aboriginal communities in
      Queensland. The data are from cohorts of children born in the 1950s-80s at
      Cherbourg, the 1960s-80s at Yarrabah and the 1970s-80s in Woorabinda, Palm Island
      and Doomadgee. Birthweights have not changed significantly in any of the
      communities and generally remain below the international level. The weights for 1
      and 5 year old children have improved significantly at Cherbourg and Palm Island,
      but have dropped significantly at Doomadgee. The overall pattern is for children
      on remote communities to have a lower %W/A and less improvement in %W/A than
      those closer to population centres. Other workers have found the same pattern
      elsewhere. These patterns of growth are probably not directly related to the
      level of general health services, but rather to other facilities available and
      attitudes of mothers to child care. The results also show that Aboriginal
      children can reach international levels of %W/A, so the poor growth in many
      communities is potentially preventable.

PMID- 8148192
TI  - Elimination of methicillin-resistant Staphylococcus aureus from a neonatal
      intensive care unit after hand washing with triclosan.
AB  - Evaluating hand wash products in terms of user acceptability and effectiveness
      against methicillin-resistant Staphylococcus aureus (MRSA) has been part of a
      long-term strategy to eliminate endemic MRSA from the neonatal intensive care
      unit at the Royal Women's Hospital (Brisbane). Following the introduction of a
      new hand wash disinfectant (triclosan 1% wt/vol), new cases of MRSA colonization
      were monitored for 12 months. In addition, the use of antibiotics, the incidence
      of multi-resistant Gram-negative cultures and neonatal infections were noted. No
      changes were made to any procedures or protocols during the trial. All babies
      colonized with MRSA had been discharged from the nursery within 7 months of the
      introduction of triclosan and in the subsequent 9 months no new MRSA isolates had
      been reported. Reduction in the use of vancomycin has resulted in a cost saving
      of approximately $A17,000. The total number of Gram-negative isolates has not
      increased, although Pseudomonas aeruginosa is now reported more often. Compared
      with the previous 12 months, fewer antibiotics were prescribed and fewer
      nosocomial infections recorded (P < 0.05).

PMID- 8148193
TI  - The Australian College of Paediatrics. Policy statement. Children's television.

PMID- 8148194
TI  - Aerosol deposition in cystic fibrosis using an aerosol conservation device and a
      conventional jet nebulizer.
AB  - The deposition of technetium radiolabelled aerosol within the lungs of 12 stable
      cystic fibrosis patients (mean age 12.7 years) was compared using the Acorn
      nebulizer and mouthpiece alone, and the Acorn nebulizer attached to the Mizer
      Aerosol Conservation Device (MACD). The total activity delivered to the patient
      using the MACD was 11.1% (+/- 7.8% s.d.) of the initial dose, compared to 5.8%
      (+/- 4.2% s.d.) with the nebulizer and mouthpiece alone (P < 0.05). With the
      MACD, 84% of the intrapulmonary dose was delivered to the peripheral regions,
      compared to 76.5% with the nebulizer and mouthpiece (P < 0.05). No significant
      correlation was found between aerosol deposition and pulmonary function. The
      Mizer Aerosol Conservation Device significantly increases both total
      intrapulmonary aerosol deposition and peripheral aerosol distribution.

PMID- 8148195
TI  - Adrenal haemorrhage: presenting as acute scrotal swelling in a neonate.

PMID- 8148196
TI  - Epstein-Barr virus associated aplastic anaemia and hepatitis.
AB  - We report a Chinese girl with Epstein-Barr virus (EBV) associated aplastic
      anaemia and hepatitis. Epstein-Barr virus genome was demonstrated in her bone
      marrow cells and EBV-specific serology suggested reactivation of EBV infection.
      She was initially treated with anti-thymocyte globulin (ATG) and
      methylprednisolone but with no haematologic response, and liver function
      continued to deteriorate. She was then treated with acyclovir. Her aplastic
      anaemia improved and hepatitis resolved, and there was eradication of EBV genome
      from her bone marrow cells.

PMID- 8148197
TI  - Cyanoacrylate-assisted foreign body removal from the ear and nose in children.
AB  - Two cases of foreign body removal using cyanoacrylate (Histoacryl blue, B. Braun
      Australia Pty. Ltd., Sydney, NSW) or tissue glue are described. Both cases
      involved children with beads, one in the external auditory meatus and the other
      in the nostril. The benefits of this technique are discussed.

PMID- 8148199
TI  - Childhood pica.

PMID- 8148198
TI  - The 'use' of children.

PMID- 8148200
TI  - Vesico-ureteric reflux.

PMID- 8148201
TI  - Vesico-ureteric reflux.

PMID- 8148202
TI  - Sudden infant death syndrome.

PMID- 8148203
TI  - The management of acute bronchiolitis.

PMID- 8148204
TI  - Chemoprophylaxis for Haemophilus and meningococcal infections. Position paper,
      Royal Australasian College of Physicians.

PMID- 8148205
TI  - Nephrology certification developed by nurses, for nurses.

PMID- 8148206
TI  - Measuring and predicting outcomes in ESRD patients.
AB  - To test the feasibility of using general health status as a practical dialysis
      outcome measure, in a longitudinal pilot study, two well-validated instruments
      were administered to patients from our dialysis unit or clinic. The instruments
      were administered three times, at eight-week intervals for seven months to 41
      hemodialysis (HD) patients. Forty-five transplant (Tx) patients were surveyed
      once as a validating control. Sociodemographic, imaging and biochemical data were
      tested as outcome predictors. Unexpected hospitalizations and adverse
      intercurrent events were used as additional outcome measures. Preliminary
      analysis shows HD patients scoring low, while Tx patients scored higher
      (healthier). These preliminary results suggest that assessment of general health
      status is a valid and practical outcome measure.

PMID- 8148207
TI  - Reaching out: bringing the human factor back to dialysis.
AB  - Prior to the early 1980s, two Winnipeg hospitals provided hemodialysis for all
      patients in Manitoba with chronic renal failure. Because no other hemodialysis
      centres existed, families were forced to relocate to the city. Because of these
      factors, the Manitoba Renal Failure Advisory Committee proposed the development
      of an outreach hemodialysis program. Under the auspices of the Health Sciences
      Centre in Winnipeg, this outreach program has evolved into the current Manitoba
      Local Centre Dialysis Program. Hemodialysis services are now available in an
      additional seven health care centres throughout Manitoba and northwestern
      Ontario. This program has benefited many and in some instances, families
      previously separated by distances of up to 500 miles have been reunited.
      Creativity has been one of the most essential ingredients in the evolution of
      this unique program.

PMID- 8148208
TI  - The development and implementation of a respite care program for paediatric
      peritoneal dialysis patients.
AB  - When a child is sent home on peritoneal dialysis, the family is faced with
      enormous challenges. Despite the coordination of community resources, there are
      few opportunities for relief from the many tasks required to keep a child home on
      dialysis. The intensity and duration of the home care required for children
      awaiting renal transplantation have often led to overwhelming parental stress,
      marital discord and burn-out. These events can lead to the detriment of the well
      being of the child and may result in a higher incidence of peritonitis. Many
      families had identified the need for some form of relief. Recognizing this, the
      staff of the home dialysis program of the Toronto Hospital for Sick Children
      (HSC) joined forces with the staff at Bloorview Children's Hospital (a chronic
      care/rehabilitation centre) to develop a respite program for these families. The
      HSC staff provided staff education, medical back-up and financed the equipment
      and supply costs while the Bloorview Hospital provided the accommodation and the
      medical and nursing staff to care for the children. In addition to providing
      parental relief, Bloorview Hospital was able to provide extended care to children
      requiring peritoneal dialysis until their parents were able to care for them at
      home. This enabled HSC to use their beds for more acutely ill children. Initial
      evaluation of the program was favourable and efforts are now being made to
      streamline the system.

PMID- 8148209
TI  - Results of the Canadian Association of Nephrology Nurses and Technicians 1992
      cross-Canada survey.

PMID- 8148210
TI  - Application of electron energy loss spectroscopy and electron spectroscopic
      imaging to aluminum determination in biological tissue.
AB  - Electron energy loss spectroscopy (EELS) is a high spatial resolution electron
      microscopic technique with the potential to quantify elements at the subcellular
      level. The presence of each element is demonstrated by the electron energy loss
      edge at the energy characteristic of that element. The area of the edge may
      indicate the quantity of element present. Electron spectroscopic imaging (ESI) is
      a similar technique generating graphic images of elemental localization in the
      specimens. An ESI of an aluminum (Al)-loaded rabbit hippocampus showed Al only in
      pyramidal cell lysosomes, but no EELS edge could be obtained. To determine the
      sensitivity of EELS for Al and to be able to adjust the instrument to optimal
      operating conditions, standards containing 50-5000 ppm Al were produced. An Al
      chloride: dicyclohexano-18-crown-6 (Al: crown) complex was synthesized. The
      purity of the complex was confirmed by nuclear magnetic resonance (NMR)
      spectroscopy and the percentage of Al in the complex was determined by
      electrothermal atomic absorption spectroscopy (ETAAS). The complex was introduced
      into a biological tissue embedding resin (Spurr medium) and appeared to be
      compatible with the resin at Al concentrations < or = 500 ppm. EELS signals from
      the Al K edge could be obtained at a spatial resolution of 3.3 nm in a 30-nm
      thick section from 2.78 x 10(-21) g of Al, representing a sample concentration of
      1% Al.

PMID- 8148211
TI  - The pharmacokinetics of piroxicam in elderly persons with and without renal
      impairment.
AB  - 1. Piroxicam pharmacokinetics were assessed in three groups of subjects: (1)
      young healthy volunteers, (2) healthy elderly subjects (mean +/- s.d. creatinine
      clearance 88 +/- 13 ml min-1), and (3) elderly patients with renal insufficiency
      (creatinine clearance 60 +/- 10 ml min-1) following the administration of
      piroxicam 20 mg as a single dose and after chronic dosing of 20 mg once daily for
      4 weeks. 2. Piroxicam and 5'-hydroxypiroxicam concentrations were measured by
      h.p.l.c. in serum and urine samples collected for 96 h after the single dose and
      for 144 h after chronic dosing. Unbound concentrations of piroxicam were
      determined by ultrafiltration. 3. Elimination half-lives, steady state
      concentrations of piroxicam and 5'-hydroxypiroxicam, clearances of total and
      unbound piroxicam, volumes of distribution normalized for body weight, and
      urinary recovery of 5'-hydroxypiroxicam were not influenced by age or renal
      function. Volumes of distribution after the single dose were significantly lower
      in women compared with men (mean +/- s.d. 10.0 +/- 2.9 l vs 12.9 +/- 5.0 l; 95%
      confidence interval of the difference 0.1 to 5.6). 4. Percent unbound piroxicam
      values were 1.46 +/- 0.3% after the single dose and 1.45 +/- 0.2% at steady
      state. There were significant reductions in clearance and clearance of unbound
      piroxicam between single and chronic doses. The half-lives of 5'-hydroxypiroxicam
      (80.9 +/- 44 h) were significantly longer than those of piroxicam (54.9 +/- 26 h)
      after chronic dosing.

PMID- 8148212
TI  - Good clinical practice--a question of balance.

PMID- 8148213
TI  - Examination of some factors responsible for a food-induced increase in absorption
      of atovaquone.
AB  - 1. Atovaquone is a potent antiprotozoal slowly and irregularly absorbed after
      administration as tablets to fasting volunteers. A series of studies was
      performed to investigate the effects of food, bile and formulation on atovaquone
      absorption. 2. In 18 healthy male volunteers, a high-fat breakfast administered
      45 min before 500 mg atovaquone as tablets increased AUC by 3.3-fold (95% CI 2.8
      4.0) and Cmax 5.3-fold (4.3-6.6) compared with fasting. 3. The absorption of
      atovaquone from tablets was examined in 12 healthy male volunteers after an
      overnight fast, following toast alone, toast with 28 g butter (LOFAT), or toast
      with 56 g butter (HIFAT). Compared with absorption when fasted, toast had no
      significant effect but LOFAT increased AUC 3.0-fold (2.1-4.2) and Cmax 3.9-fold
      (2.6-5.8). HIFAT increased AUC 3.9-fold (2.7-5.5) and Cmax 5.6-fold (3.8-8.4). 4.
      The absorption of atovaquone was examined in nine healthy fasting male volunteers
      from tablets, an aqueous suspension, and an oily solution/suspension in miglyol
      (fractionated coconut oil). Compared with tablets, AUC following the aqueous
      suspension was increased 1.7-fold (1.0-2.7) and Cmax 2.4-fold (1.7-3.5).
      Following miglyol, AUC was increased to the same extent but Cmax was only
      increased 1.8-fold (1.2-2.6). 5. Atovaquone absorption was examined in eight
      healthy fasting male volunteers following an i.v. infusion of cholecystokinin
      octapeptide (CCK-OP) which decreased gallbladder volume by 82% (73%-90%) on
      occasion 1 or saline on occasion 2. AUC(0,12) was increased following CCK-OP by
      1.6-fold (1.1-2.4) and Cmax by 1.5-fold (0.98-2.4).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8148214
TI  - The influence of gender and sex steroid hormones on the plasma binding of
      propranolol enantiomers.
AB  - 1. Plasma binding of tritium-labelled racemic propranolol (P) was measured by
      equilibrium dialysis. The unbound enantiomers were separated by h.p.l.c. after
      chiral derivatization. The binding of (-)-P was higher than that of (+)-P. 2.
      Contrary to previous suggestions, a sex difference in the plasma binding of the P
      enantiomers (9 young women, 12 young men) was not observed. The unbound
      percentage of (-)-P was 9.2 +/- 1.8 (mean +/- s.d.) in women vs 9.1 +/- 1.7 in
      men; for (+)-P it was 10.8 +/- 1.8 vs 10.8 +/- 2.1. 3. In the nine women, the
      binding did not change with fluctuating plasma oestradiol concentrations during
      the menstrual cycle. Testosterone cypionate doubled the circulating
      concentrations of testosterone in eight men but had no effect on P binding. 4.
      Ethinyl oestradiol (50 micrograms day-1) alone or together with norethindrone
      (OCD) in eight of the women produced an increase in the unbound percentage of
      both (-)-P (11.4 +/- 2.6 vs 9.5 +/- 1.6 for control; P < 0.001) and (+)-P (13.2
      +/- 2.5 vs 11.2 +/- 1.5 for control; P < 0.001). This was due to a decrease in
      the plasma concentrations of alpha 1-acid glycoprotein from 0.54 +/- 0.11 mg ml-1
      in control to 0.37 +/- 0.08 mg ml-1 (P < 0.001) during ethinyl oestradiol
      treatment. 5. Enantioselectivity in the unbound fraction of P increased with
      increasing total binding from a (-)/(+)-ratio of 0.93 at 84% binding to a (-)/(+)
      ratio of 0.78 at 94% binding (P < 0.001).

PMID- 8148215
TI  - A double-blind, placebo-controlled interaction study between oxcarbazepine and
      carbamazepine, sodium valproate and phenytoin in epileptic patients.
AB  - 1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT)
      on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12
      epileptic patients taking one of these drug as monotherapy. 2. Each patient took
      a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC
      300 mg thrice daily and matched placebo in random order. 3. Seven untreated
      patients, acting as controls, were prescribed the single OXC dose and 3 weeks'
      active treatment only. 4. In those patients completing the study, the area under
      the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ),
      the active metabolite of OXC, was significantly lower in the CBZ-treated group
      than in controls (P < 0.05). 5. No other differences in AUCs or elimination half
      lives for OHCZ were found between treated and untreated patients following single
      or multiple OXC dosing. 6. Median AUCs of CBZ, VPA and PHT during a dosage
      interval did not differ significantly after treatment with OXC and placebo. 7.
      Ten patients completing the study complained of side-effects during treatment
      with OXC compared with one taking placebo (P < 0.01). 8. There were no important
      changes in cognitive function testing during administration of OXC compared with
      placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic
      patients receiving CBZ, VPA or PHT without producing a clinically relevant
      pharmacokinetic interaction.

PMID- 8148216
TI  - Acoustic rhinometry compared with posterior rhinomanometry in the measurement of
      histamine- and bradykinin-induced changes in nasal airway patency.
AB  - 1. Acoustic rhinometry is a relatively new method for objectively assessing nasal
      airway patency. In this paper we compare acoustic rhinometry with active
      posterior rhinomanometry. 2. Twenty normal healthy volunteers underwent nasal
      challenge with either histamine or bradykinin, 100 micrograms to 1000 micrograms,
      and responses were assessed by acoustic rhinometry. A further 20 subjects
      received identical nasal challenges and responses were assessed by active
      posterior rhinomanometry. 3. On a subsequent occasion, the subjects challenged
      previously with histamine, were given the selective H1-receptor antagonist,
      cetirizine, 10 mg orally, 3 h before repeat nasal challenge with histamine, 100
      1000 micrograms. Again, responses were assessed by active posterior
      rhinomanometry and acoustic rhinometry. 4. The acoustic reflection measurements
      and the nasal airway resistance measurements showed comparable, significant dose
      related changes in nasal patency to both histamine and bradykinin. Pretreatment
      with cetirizine blocked the histamine-induced change in nasal patency as measured
      by both methods. 5. We conclude that acoustic rhinometry has a number of
      advantages over posterior rhinomanometry. It is quick to perform, requires
      minimal subject co-operation and gives a reliable objective, measurement of dose
      related changes in nasal airway patency before and after pharmacological
      treatment.

PMID- 8148217
TI  - An assessment of lacidipine and atenolol in mild to moderate hypertension.
AB  - 1. The aim of this randomised, double-blind four way crossover study was to
      assess the interaction between the new calcium antagonist, lacidipine and
      atenolol, in patients with mild to moderate hypertension. 2. Sitting blood
      pressure at 4 h post-dosing with lacidipine (4 mg) and atenolol (100 mg) alone
      was significantly lower compared with placebo (137/89 +/- 3/3 mmHg; 142/89 +/-
      5/3 mmHg; and 154/98 +/- 5/3 mmHg respectively; P < 0.001). Co-administration of
      both drugs produced a significant additive effect compared with atenolol and
      lacidipine alone (124/80 +/- 4/2 mmHg; P < 0.002). 3. Heart rate on treatment
      with lacidipine alone was significantly greater at 4 h compared with placebo (86
      +/- 1 beats min-1 and 74 +/- 2 beats min-1 respectively; P < 0.001). When both
      drugs were used in combination, there was a significant decrease in pulse rate
      compared with lacidipine alone (58 +/- 1 beats min-1 and 86 +/- 1 beats min-1
      respectively; P < 0.001). 4. Home blood pressure recordings confirmed the
      statistically significant reduction in blood pressure on co-dosing (120/82 +/-
      10/2 mmHg) compared with lacidipine (140/92 +/- 5/3 mmHg) and atenolol (146/90 +/
      6/3 mmHg) given alone (P < 0.05). 5. Lacidipine alone produced a significant
      exercise tachycardia compared with atenolol alone and the atenolol/lacidipine
      combination (97 +/- 8 beats min-1; 65 +/- 4 beats min-1 and 75 +/- 7 beats min-1
      respectively; P < 0.001). Exercise tolerance was not adversely affected by the co
      administration of both lacidipine and atenolol.

PMID- 8148218
TI  - Colestipol at varying dosage intervals in the treatment of moderate
      hypercholesterolaemia.
AB  - 1. Bile acid sequestrants such as colestipol are effective lipid lowering agents
      but have a poor reputation for tolerability particularly when administered at the
      originally recommended doses. We have investigated a low dosage regimen with
      varying dosage intervals in order to assess efficacy and tolerability. 2. This
      double-blind, placebo controlled, parallel group study was conducted to
      investigate the effect of varying administration schedules of colestipol (10 g
      daily), against placebo in reducing LDL cholesterol levels in patients with
      moderate hypercholesterolaemia on the American Heart Association step 1 diet. 3.
      Colestipol or matched placebo, was administered as 5 g twice daily (COL am/pm) or
      10 g once daily in the morning (COL am) or evening (COL pm) at fixed times with
      meals. 4. All 98 patients who entered the initial 16 week dietary phase,
      subsequently entered the 12 week active treatment phase and were randomised to
      placebo or active treatment and to one of the three treatment schedules. Fasting
      lipid profiles were performed every 4 weeks during both phases. 5. All active
      treatments significantly reduced LDL and total cholesterol compared with placebo
      (COL am: 17% and 10%, COL pm: 18% and 10%, COL am/pm: 19% and 12% (P = 0.0001)).
      HDL cholesterol rose significantly with COL am (5% (P = 0.021)) and COL am/pm (7%
      (P = 0.002)) when compared with placebo while a marginal increase was seen with
      COL pm (4% (P = 0.063)). Colestipol tended to increase serum triglyceride
      concentrations but the changes were not significant.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8148219
TI  - Effects of ACE inhibitors on oxidation of human low density lipoprotein.
AB  - Oxidation of low density lipoprotein (LDL) may be instrumental in the development
      of atherosclerosis. We have examined the effect of the angiotensin converting
      enzyme (ACE) inhibitors captopril and quinaprilat and the -SH containing compound
      N-acetylcysteine on LDL oxidation. Oxidation of isolated human LDL was initiated
      with CuCl2. Conjugated diene formation (monitored spectrophotometrically at 234
      nm) gave a measure of LDL oxidation. Captopril inhibited LDL oxidation but
      quinaprilat did not. The lag phase to the rapid increase in absorbance at 234 nm
      determined was 109 (65-157) min median and range for control samples and rose to
      209 (168-305) min with captopril 10 microM, a ratio of 2.1:1 for drug to control
      (P = 0.01). N-acetylcysteine had a similar effect to captopril (drug to control
      lag time ratio 2.0:1, with NAC 10 microM), i.e. suggesting resistance to
      oxidation was due to the -SH group of both drugs. Captopril may have a
      potentially anti-atherosclerotic property not shared by other ACE inhibitors.

PMID- 8148220
TI  - Oxidative activation of proguanil and dapsone acetylation in Thai soldiers.
AB  - The prevalence of putative poor metaboliser (PM) phenotypes of proguanil
      oxidation in Caucasian populations is 3-10%. The PM frequency in Oriental
      populations is unknown. In this study the plasma metabolic ratios of proguanil
      and dapsone to their principal metabolites cycloguanil and monoacetyldapsone were
      determined in Thai soldiers receiving antifolate drug combinations for malaria
      prophylaxis. The distribution ratio of proguanil to cycloguanil (PROG/CYC) was
      highly skewed with no evidence of bimodality. Assuming subjects with a PROG/CYC
      ratio greater than 10 are PMs from studies in Caucasians, the incidence of PMs in
      the soldiers would be 18% (30 of 170). The mean PROG/CYC ratio for PMs in the
      Thai soldiers was 31.2 +/- 28.9 (n = 30) compared with 25.5 +/- 2.5 (n = 3) in a
      study of Caucasians. The corresponding values for putative EMs were 5.4 +/- 2.1
      (n = 140) and 2.4 +/- 0.2 (n = 134). Similar to other Oriental populations, Thais
      were found to be predominantly (76%, 173 of 228) rapid acetylators of dapsone.

PMID- 8148221
TI  - Zidovudine pharmacokinetics in zidovudine-induced bone marrow toxicity.
AB  - 1. The major adverse effect of zidovudine (ZDV) is haematological toxicity which
      results in anaemia and granulocytopenia. The aim of the present study was to
      investigate if HIV-positive patients developing erythroid aplasia/hypoplasia are
      exposed to higher plasma concentrations of ZDV owing to impaired hepatic
      metabolism to the major metabolite, 3'-azido-3'-deoxy-5'-beta-D
      glucopyranuronosylthymidine (GZDV). 2. Twelve HIV-positive male patients were
      studied, six having developed bone marrow aplasia/hypoplasia within the first 6
      months of ZDV therapy. Each of the patients exhibiting toxicity were matched for
      age, weight, risk factors for HIV infection and disease stage with patients who
      had no evidence of early bone marrow toxicity. 3. ZDV was administered orally in
      doses of 3-10 mg kg-1 and blood samples taken at intervals to 6 h. Urine was
      collected over the whole 6 h period. ZDV and GZDV were assayed by h.p.l.c. 4.
      There were no significant differences in the pharmacokinetic parameters between
      the two groups of patients. For patients with early bone marrow toxicity the
      elimination half-life of ZDV was 1.10 +/- 0.16 h with an oral clearance of 2752
      +/- 1031 ml min-1 compared with values of 1.06 +/- 0.18 h and 2843 +/- 730 ml min
      1 seen in the control group. Similarly there was no significant difference in the
      pharmacokinetics of GZDV or the urinary ratio of GZDV to ZDV. 5. Therefore,
      despite the fact that ZDV toxicity to haematopoietic progenitor cells has been
      previously shown to be dose related, there was no indication from this study that
      it is directly related to plasma concentrations of ZDV.

PMID- 8148222
TI  - Disposition of clozapine in man: lack of association with debrisoquine and S
      mephenytoin hydroxylation polymorphisms.
AB  - A large interindividual variability has previously been demonstrated in the
      bioavailability, steady-state plasma concentrations and clearance of clozapine,
      an atypical neuroleptic drug. To evaluate the importance of genetic factors in
      the metabolism of clozapine, its disposition after a single oral dose of 10 mg
      was studied in 15 healthy Caucasian volunteers. Five of the subjects were poor
      metabolisers (PM) of debrisoquine, five were PM of S-mephenytoin, and the
      remaining five were extensive metabolisers (EM) of both probe drugs. There was a
      10-fold interindividual variation in Cmax and a 14-fold variation in AUC(0, 24)
      of clozapine among the 15 subjects studied. The mean (s.d.) Cmax was 117 (81)
      nmol l-1 and the mean AUC(0,24) value was 890 (711) nmol l-1 h. The value of
      t1/2,z varied 3-fold with a mean (s.d.) of 13.3 (5.0) h. There were no
      significant differences in the plasma concentrations or any of the
      pharmacokinetic parameters of clozapine between PM and EM of debrisoquine, or
      between the two S-mephenytoin hydroxylation phenotypes. We conclude that neither
      of the major genetic polymorphisms of oxidative drug metabolism contribute to the
      large interindividual variability in clozapine pharmacokinetics.

PMID- 8148223
TI  - The pharmacokinetics of ketorolac enantiomers following intramuscular
      administration of the racemate.
AB  - A single dose of racemic ketorolac (30 mg of tromethamine salt, Toradol) was
      administered by bolus intramuscular injection to four young, healthy volunteers.
      The concentrations of total (bound plus unbound) (R)- and (S)-ketorolac were
      measured in plasma for 9 h after dosing. The mean +/- s.d. clearance of (S)
      ketorolac (45.9 +/- 10.1 ml h-1 kg-1) exceeded (P = 0.0032) that of the (R)
      enantiomer (19.0 +/- 5.0 ml h-1 kg-1). The mean +/- s.d. AUC ratio for (S)
      ketorolac:(R)-ketorolac (0.442 +/- 0.043) was significantly different from unity
      (P = 0.0001). The steady-state volume of distribution of (S)-ketorolac (0.135 +/-
      0.022 l kg-1) was significantly different (P = 0.0013) from that of its optical
      antipode (0.075 +/- 0.014 l kg-1) and the half-lives of (S)- and (R)-ketorolac
      (2.35 +/- 0.23 h and 3.62 +/- 0.79 h, respectively) were also significantly
      different (P = 0.026). These data indicate that the disposition of ketorolac in
      man is subject to marked enantioselectivity and, because of possible differences
      in biological activity of (S)- and (R)-ketorolac, emphasize the need to monitor
      separate stereoisomer concentrations of the drug if pharmacological data are to
      be interpreted correctly.

PMID- 8148224
TI  - Neither cimetidine nor probenecid affect the pharmacokinetics of tenoxicam in
      normal volunteers.
AB  - The effect of pretreatment with cimetidine (1 g day-1, 7 days) and of probenecid
      (1 g twice daily, 4 days) on the pharmacokinetics of tenoxicam (single oral dose,
      20 mg) was studied in six healthy volunteers. Cmax was increased significantly
      when tenoxicam was given with probenecid (2.8 micrograms ml-1 alone, 3.5
      micrograms ml-1 after probenecid; P < 0.005). No other pharmacokinetic parameters
      were altered significantly by either drug. It is concluded that neither
      cimetidine nor probenecid affects the pharmacokinetics of tenoxicam in a
      clinically important way.

PMID- 8148225
TI  - The effect of ferrous sulphate on the absorption of norfloxacin, ciprofloxacin
      and ofloxacin.
AB  - The effect of ferrous sulphate on the absorption of norfloxacin, ciprofloxacin
      and ofloxacin was studied in three separate, two-period crossover trials, each
      involving eight healthy volunteers. After an overnight fast, a single dose of
      norfloxacin (400 mg), ciprofloxacin (500 mg) or ofloxacin (400 mg) was
      administered with and without ferrous sulphate (corresponding to 100 mg elemental
      iron). The absorption of all the fluoroquinolones studied was significantly
      reduced when they were co-administered with ferrous sulphate. The reduction in
      the area under the plasma drug concentration-time curve from 0 to 24 h was most
      marked in the case of norfloxacin, while ofloxacin was least affected by ferrous
      sulphate. The AUC of norfloxacin was reduced by 73% (P < 0.001) and its peak
      plasma concentration by 75% (P < 0.01) by concomitant ingestion of ferrous
      sulphate. The AUC and peak plasma concentration of ciprofloxacin were reduced by
      57% (P < 0.001) and 54% (P < 0.01), respectively, by ferrous sulphate.
      Concomitant ingestion of ferrous sulphate reduced the AUC and peak plasma
      concentration of ofloxacin by 25% (P < 0.01) and 36% (P < 0.01), respectively.
      Similar results were obtained with respect to the urinary recoveries of each
      fluoroquinolone. We recommend that norfloxacin and ciprofloxacin should not be
      taken together with ferrous sulphate. It would also be advisable not to take
      ofloxacin with ferrous sulphate, especially if the organism causing infection is
      only moderately susceptible.

PMID- 8148226
TI  - Plasma concentrations of betamethasone after topical application of betamethasone
      17-valerate: comparison with oral administration.
AB  - Plasma concentrations of betamethasone were measured by r.i.a. after oral
      administration of 0.6 mg betamethasone and topical application of betamethasone
      17-valerate in the same five healthy subjects. Betamethasone 17-valerate was
      prepared as a suspension in medical grade pressure sensitive adhesive and applied
      to a 100 cm2 area on the back for 28 h. Mean maximum plasma concentrations were
      5.0 and 0.24 ng ml-1 and mean AUC values were 75.4 and 7.74 ng ml-1 h after oral
      and topical administrations, respectively. The mean plasma elimination half-life
      of betamethasone after the removal of topical betamethasone 17-valerate was 16.6
      h which was twice that after oral administration, 8.1 h. Betamethasone 17
      valerate may require application to the skin more than twice daily.

PMID- 8148227
TI  - Blood concentrations of dopexamine in patients during and after orthotopic liver
      transplantation.
AB  - Blood concentrations of dopexamine were measured in five female patients during
      and after orthotopic liver transplantation. Each patient received a continuous
      infusion of the drug (2 micrograms kg-1 min-1), starting at induction of
      anaesthesia and finishing 48 h afterwards. Blood concentrations of dopexamine
      increased rapidly at the start of the infusion, to a mean (range) value of 64 (40
      150) ng ml-1 after 20 min. Blood concentrations of dopexamine increased further
      during the anhepatic period of surgery, to 236 (180-410) ng ml-1. On reperfusion
      of the donor liver, concentrations of dopexamine decreased rapidly, reaching
      similar values to the maximum seen during the dissection period. Steady-state was
      not reached during either the dissection or anhepatic periods. From 1-2 h after
      revascularisation the mean (range) steady-state concentration was 85 (69-102) ng
      ml-1 corresponding to a mean (range) clearance of 24 (20-29) ml min-1 kg -1.
      These results suggest that the liver plays a significant role in the clearance of
      dopexamine.

PMID- 8148229
TI  - Effects of a thromboxane receptor antagonist on prostaglandin D2 and histamine
      induced bronchoconstriction in man.
AB  - Many prostanoids including are prostaglandin (PG) F2 alpha and PGD2 are potent
      bronchoconstrictor agents. There is evidence to suggest that airway thromboxane
      (TP) receptor may act as a common receptor for their bronchoconstrictor actions.
      We tested the hypothesis that inhaled prostaglandin (PG) D2-induced
      bronchoconstriction is mediated by interacting with the TP receptor antagonist,
      ICI 192605, on the bronchoconstrictor response to inhaled PGD2 in a double-blind,
      placebo-controlled and crossed-over trial in normal subjects. The effect of ICI
      192605 on histamine induced bronchoconstriction served as control for non
      specific bronchodilatory actions. The study had two phases; the first consisted
      of two inhaled PGD2 challenge study days, and the second phase was that of
      inhaled histamine. Each study day was separated by at least a week. On each study
      day, the challenge tests were carried out 30 min after ingestion of 100 mg ICI
      192605 or placebo. Doubling concentrations of agonist were given till more than
      35% fall in post-diluent specific airway conductance (sGaw) occurred. The
      concentration needed to cause a fall in a sGaw of 35% post-diluent value
      (PC35sGaw) was then determined from linear interpolation of the log dose
      response. Eight male subjects (median age 26, range 20-35 years) completed the
      study. ICI 192605 did not change baseline airway calibre 30 min after ingestion
      on either PGD2 or histamine study days. ICI 192605 significantly shifted the dose
      response curve to inhaled PGD2 to the right by a median of 3.4 fold (Wilcoxon
      rank sign test, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148228
TI  - Pharmacokinetic study of yohimbine and its pharmacodynamic effects on salivary
      secretion in patients treated with tricyclic antidepressants.
AB  - The pharmacokinetic parameters and the time course of the effect after acute oral
      administration of yohimbine on salivary secretion in patients treated with
      tricyclic antidepressants were investigated. Yohimbine (10 mg) increased both
      salivary outflow and plasma noradrenaline levels for 4 h. Pharmacokinetic
      parameters (t1/2, tmax, Cmax and AUCexp) and plasma concentrations of
      noradrenaline were higher in patients treated with tricyclic antidepressants than
      in controls. At this dose, yohimbine induced a relatively large number of side
      effects. A lower dose (4 mg) increased salivary secretion for 3 h without any
      side effects in patients treated with tricyclic antidepressants but not in
      healthy volunteers. These data describe an interaction between yohimbine and
      tricyclic antidepressants and thus show that a relatively low dose (4 mg) of
      yohimbine could be useful in the treatment of dry mouth due to tricyclic
      antidepressants.

PMID- 8148230
TI  - In vivo 31P MRS of experimental tumours.
AB  - More than 50% of cancers fail to respond to any individual treatment and tumour
      follow-up after treatment plays a major role in routine therapy planning and
      pharmacological research. Today, MRS is the only technological approach providing
      non-invasive access to tumour biochemistry. Ten years ago, expectations were
      raised concerning 31P MRS as an exciting and promising technical approach to the
      study of tumours. However the expectations have not always come to fruition. How
      close are we now to seeing routine 31P NMR in clinical oncology? This review of
      the 127 published papers shows spectroscopy results in more than 150 experimental
      animal tumour models. These tumour/host/treatment systems provide us with a
      useful basis to evaluate the current state of the art, summarize the basic
      knowledge presently available, determine the key points underlying the present
      disappointment of some clinical oncologists and stimulate new basic research. The
      information collected concerns the discussion of the reliability of experimental
      models in oncology, the technical improvement of magnetic resonance technology
      and the monitoring of bioenergetic status, pH regulation and phospholipid
      metabolism in treated and untreated tumours. Recent advances (two-thirds of the
      papers have been published in the last 5 years) seem to provide more optimistic
      perspectives than those generally accepted a few years ago, in the depressing
      period following early pioneering work.

PMID- 8148231
TI  - Localized T1 measurements using an inversion-recovery OSIRIS method.
AB  - This work presents a new method for localized T1 measurements, based upon the
      OSIRIS scheme. It relies on the use of a non-selective 180 degrees pulse applied
      before the OSIRIS preparation cycle. The accuracy of the method has been verified
      with test tubes and in vivo for two nuclei, 1H and 19F. The accuracy of the T1
      values is discussed, as well as possible applications of the inversion-recovery
      method to non-invasive in vivo pO2 measurements.

PMID- 8148232
TI  - In situ 13C NMR quantification of hepatic glycogen.
AB  - We report on the 13C NMR visibility of the C-1 glycosidic carbon of alpha
      particulate glycogen in perfused rat liver. We used rats fed ad libitum, animals
      refed after a 48 h fast with a sucrose supplement with or without glucocorticoid
      treatment, and gsd/gsd rats with a hepatic glycogen storage disease due to
      phosphorylase kinase deficiency. Thus we studied a wide range of glycogen levels
      (25-140 mg/g liver). All livers were perfused with 15 mM glucose, to maintain
      constant glycogen levels. Failure to activate glycogen phosphorylase ensures
      stable glycogen levels in gsd/gsd livers. Natural abundance 13C NMR signals were
      calibrated against a phantom containing a fixed amount of glycogen. Accumulated
      free induction decays were analysed after Fourier transformation by numerical
      integration, or by direct analysis of the signal in the time domain using a non
      iterative method based on singular value decomposition. NMR quantification of the
      glycogen correlated well with the chemical determination over the whole
      concentration range. However, the precision (reproducibility) of glycogen
      determinations (be it by chemical methods or by NMR spectroscopy) may pose
      problems. Authors should be encouraged to report systematically on the precision
      of their methods.

PMID- 8148233
TI  - In vivo 19F one-dimensional chemical shift imaging study of isoflurane uptake in
      rabbit brain.
AB  - 19F one-dimensional chemical shift imaging and one-pulse techniques were used to
      follow the uptake of isoflurane in rabbit brain in vivo. Brain isoflurane
      appeared mainly in two adjacent slices of cerebral cortex. Both slices showed
      increase in anesthetic content at similar rates. A biphasic first-order uptake
      pattern with an initial fast component and a slower rate for the duration of the
      uptake was observed by the one-pulse technique. Only the slower kinetic was
      followed by chemical shift imaging due to constraints on temporal resolution.
      Anesthetic levels in arterial blood reached equilibrium significantly earlier
      than in brain, suggesting a 'restricted' diffusion into brain tissue for this
      agent.

PMID- 8148234
TI  - Non-invasive investigation of parenchymal liver disease using 31P NMR
      spectroscopy.
AB  - Four 31P NMR spectroscopy parameters were measured non-invasively in the liver of
      11 healthy pigs and 9 pigs with CCl4-induced liver disease: (i) absolute molar
      concentration of phosphorous metabolites; (ii) pH based on the chemical shift of
      the P(i) peak; (iii) T1 of the peaks in the 31P NMR spectrum; and (iv) changes in
      ATP, P1 and phosphomonoester after fructose administration. Liver disease was
      verified by histology and blood chemistry. The concentration of ATP decreased
      from 3.0(2.8-3.1) to 2.0(2.0-2.4) mM (median and quartiles) when liver disease
      was induced (p < 0.05). The concentration of phosphodiesters (PDEs) decreased
      from 14.8(11.4-19.5) to 8.7(7.4-11.6) mM (p < 0.05). pH increased by 0.1 unit. T1
      relaxation times for the gamma-, alpha- and beta-ATP peaks increased from 320(249
      471) to 577(506-638) ms (p < 0.01), from 765(611-786) to 906(820-1058) ms (p <
      0.05) and from 402(327-509) to 579(543-743) ms (p < 0.01), respectively, while T1
      for the PDE peak decreased from 2204(1909-2404) to 1758(1502-1894) ms (p < 0.05).
      In the healthy animals injection of fructose was followed by a reduction of ATP
      (beta-ATP). In diseased livers this reduction was significantly smaller. In
      conclusion, it was possible non-invasively to show differences between healthy
      and diseased livers in all NMR parameters evaluated. This means that 31P NMR
      spectroscopy may have a potential as a non-invasive diagnostic method for
      studying liver disease.

PMID- 8148235
TI  - Tissue barriers, immunosuppressive microenvironments, and privileged sites: the
      eye's point of view.
AB  - Immune privilege exists at numerous sites in the body. It is becoming
      increasingly clear that privilege is extended to foreign tissues implanted at
      privileged sites by active regulatory mechanisms, rather than because implanted
      tissues are hidden from recognition by cells of the immune system. Recent
      experimental analysis of privilege has focused on regional tissue factors that
      participate in creating the privileged status. Local barriers are being more
      fully described, barriers that restrict, but do not prevent, afferent and
      efferent communication between a privileged site and the systemic immune
      apparatus. In addition, cytokines and mediators are being discovered at local
      sites, and these agents appear to create novel microenvironments that act on
      migrating cells of the lymphoreticular system and thereby modify both the
      induction and expression of immunity to antigenic materials that are introduced
      into, or arise within, privileged sites. This review summarizes many recent
      studies, and attempts to place in the broader context of systemic immunity what
      has been learned in the recent past about the unique forms of immunity that
      attend foreign tissue grafts and other types of antigenic materials placed
      experimentally in privileged sites. Particular emphasis is placed on reconciling
      (a) the requirements of various organs and tissues for immune protection against
      invading pathogens with (b) the vulnerability of certain organs and tissues to
      immunopathogenic processes that inadvertently inflict tissue injury and
      dysfunction.

PMID- 8148236
TI  - In vitro culture allows splenic dendritic cells to reach their full potential for
      T-cell activation.
AB  - Splenic dendritic cells (DCs), bone marrow-derived cells of the presumed
      monocyte/macrophage lineage, have been used as freshly prepared cells, as well as
      after overnight culture, to analyze their capacity to activate T cells in vitro
      with and without cognate antigen being present in the culture. Cultured DCs were
      found to possess potent accessory properties in vitro, displaying the abilities
      1) to activate naive, syngeneic T cells in the absence of cognate antigen, and,
      after being derivatized with the hapten, dinitrofluorobenzene (DNFB), and 2) to
      sensitize unprimed, hapten-specific T cells such that the latter were able to
      mediate DNFB-dependent contact hypersensitivity in normal, unprimed mice. Freshly
      prepared splenic DCs also displayed accessory cell function; in the presence of
      the super-antigen, staphylococcal enterotoxin B, fresh DCs induced T-cell
      proliferation, and, when derivatized with DNFB, fresh DCs activated hapten
      specific T cells from in vivo-primed mice. However, in both of these assays,
      fresh DCs were quantitatively inferior to cultured DCs. We conclude that splenic
      DCs can exist in two functional forms in vitro, and we propose that the
      functional properties displayed by freshly obtained cells correspond to the
      capabilities constitutively displayed by splenic DCs in the normal, unstimulated
      spleen. In these regards, splenic DCs appear to resemble Langerhans cells after
      the latter have been exposed to similar culture conditions. The possible
      relationships between Langerhans cells and DCs are discussed in terms of the role
      of the cytokine-containing microenvironment in dictating distinct functional
      properties of antigen-presenting cells.

PMID- 8148237
TI  - Aqueous humor inhibits epidermal cell antigen-presenting function.
AB  - Aqueous humor (AH) is a complex biological fluid containing factors that mediate
      a number of activities that may contribute to immune privilege in the anterior
      chamber of the eye. To determine whether AH may inhibit dendritic cell antigen
      presenting function, we evaluated the ability of AH to alter the ability of
      freshly obtained epidermal cell (EC) preparations enriched for Langerhans cells
      (LC) to present tumor-associated antigens (TAA) derived from the S1509a spindle
      cell tumor for elicitation of a delayed-type hypersensitivity (DTH) reaction in
      tumor-immune mice. Fresh EC preparations contain 2-5% LC. Exposure of EC to media
      containing AH for 2 hours prior to TAA-pulsing and injection into a hind footpad
      of tumor-immune mice resulted in a dose-dependent decrease in the DTH response.
      Aqueous humor contains transforming growth factor-beta (TGF beta), primarily TGF
      beta 2 as determined by specific neutralization of activity in the Mv 1 Lu cell
      assay. However, exposure of EC to TGF beta 2 in this fashion prior to TAA-pulsing
      had no effect on the degree of hypersensitivity elicited. Furthermore,
      preincubation of AH with neutralizing antiserum to TGF beta 2 had no effect on
      the ability of AH to inhibit LC antigen-presenting function. Mixing of AH-exposed
      non-TAA-pulsed EC with TAA-pulsed EC not exposed to AH prior to footpad challenge
      did not diminish the DTH response, suggesting that carryover of AH into the
      footpad was not responsible for the inhibition observed.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8148238
TI  - Murine Pam 212 cutaneous squamous cell carcinoma is nonimmunogenic in normal
      syngeneic hosts and resistant to immune effector mechanisms.
AB  - We established a mouse model of cutaneous squamous cell carcinoma (SCC) using the
      Pam 212 cell line to study antitumor immunity in normal syngeneic hosts. In
      vitro, Pam 212 cells expressed very low levels of class I major
      histocompatibility complex (MHC) antigen; interferon-gamma (IFN-gamma)
      significantly increased the expression of this antigen. In vivo, Pam 212 tumors
      grew progressively in normal BALB/c hosts and resembled poorly differentiated
      human cutaneous SCC. Immunization of normal syngeneic hosts with irradiated,
      class I-negative or -positive Pam 212 cells failed to prevent tumor growth or
      induce specific cytotoxic T lymphocytes (CTL). However, Pam 212 tumor cells were
      rejected by C3H allogeneic mice, indicating adequate and functional class I
      antigen expression in vivo. Rejection of Pam 212 tumors by C3H hosts was in part
      dependent on CD8+ CTL lysis, as alloreactive anti-H-2d CTL lysed class I-positive
      Pam 212 cells, demonstrating that Pam 212 cells express functional class I MHC
      antigens. Both class I-positive and -negative Pam 212 cells were resistant to
      natural killer cell lysis. We hypothesize that ineffective syngeneic immune
      responses against Pam 212 cells may involve multiple mechanisms: inability of Pam
      212 cells to elicit a primary immune response, as well as resistance to cell
      mediated lysis.

PMID- 8148239
TI  - Modification of T-lymphocyte subsets in peripheral blood, the liver, and the
      spleen during liver regeneration after partial hepatectomy of mice.
AB  - Flow cytometry analysis was performed to investigate the modifications to the T
      lymphocytes in peripheral blood, the spleen, and two intrahepatic lymphocyte
      fractions--the intrahepatic lymphocyte fraction 1 (IHL Fr.1), which is easily
      washed out from the liver by perfusion of collagenase solution, and the
      intrahepatic lymphocyte fraction 2 (IHL Fr.2), which remains in the liver after
      the perfusion--occurring in the liver regeneration process after partial
      hepatectomy of mice. The following findings were obtained: 1) The nontreated
      murine liver contains Thy 1.2+ cells, alpha beta TCR+ cells, gamma delta TCR+
      cells, CD4+ cells, and CD8+ cells. 2) The percentage of each T-cell subset in IHL
      Fr.1 shows an intermediate value between that in the peripheral blood lymphocytes
      (PBL) and that in the IHL Fr.2. 3) One day after partial hepatectomy, the Thy
      1.2+ cells, alpha beta TCR+ whole cells, and CD4+ cells in IHL Fr.2 all showed a
      transient, yet significant, decrease, but did not reveal any major change in the
      other fractions. 4) Both the alpha beta TCR dull+ cells and the CD8+ cells showed
      practically no change after partial hepatectomy in any of the fractions. This
      indicates that the alpha beta TCR dull+ cell/alpha beta TCR+ whole cell and the
      CD8+ cell/CD4+ cell ratios show a significant increase 1 day after partial
      hepatectomy only in the IHL Fr.2. Double-positive cells, which were scarcely
      found in the spleen of nontreated mice, appeared in the spleen after partial
      hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148240
TI  - Failure to inhibit endotoxin-induced uveitis with antibodies that neutralize
      tumor necrosis factor.
AB  - Many of the effects of bacterial endotoxin are attributed to the cytokines that
      it induces. Tumor necrosis factor alpha (TNF alpha) may be responsible for many
      of the pathophysiologic effects of endotoxin because antibodies that neutralize
      TNF alpha reduce endotoxin-induced mortality in experimental animals and many of
      the activities of endotoxin can be mimicked by the infusion of TNF alpha.
      Accordingly, we tested the ability of an antibody that neutralizes TNF alpha in a
      well characterized rat model, endotoxin-induced uveitis. Rats receiving
      subcutaneous endotoxin had a prompt rise in serum TNF alpha that was eliminated
      by the monoclonal antibody. Small quantities of TNF alpha were detectable in
      aqueous humor after either subcutaneous or intravitreal injection of endotoxin.
      Endotoxin-induced uveitis as quantitated by cells and protein in aqueous humor
      was, however, not affected by the antibody. Similarly, intraocular inflammation
      was not reduced by the intravitreal injection of the neutralizing antibody.
      Although TNF alpha may mediate many of the systemic effects of endotoxin, its
      role in the intraocular inflammatory effects of endotoxin should be questioned.

PMID- 8148241
TI  - The UK's AIDS rate.

PMID- 8148242
TI  - Discrimination. Racism in nursing.

PMID- 8148243
TI  - Discrimination. Accepting differences.

PMID- 8148244
TI  - Change, revolt and the student nurse.
AB  - Nurse education is facing great changes which challenge traditional methods of
      training and educating student nurses. Project 2000, college amalgamation and
      links with universities have coincided with a drive towards increasing
      opportunities for nurses to achieve graduate status and generally raise the
      academic status of nursing as a profession. The student nurses caught up in these
      changes must be more than passive recipients of information, or dissatisfaction
      will occur. The author considers the unsettling effect of change on students and,
      through examination of factors such as teachers' attitudes and adult education,
      concludes that student participation in programme planning and policy-making must
      become more widespread of educators are to avoid dissatisfaction turning to
      revolt.

PMID- 8148245
TI  - Hormone replacement therapy (HRT) (continuing education credit).

PMID- 8148246
TI  - Psychosocial care of HIV-positive people.
AB  - HIV-positive people continue to be faced with an array of social and personal
      prejudices, most of which are based on ignorance and fear. The author explores
      how such attitudes affect HIV-positive people, and offers advice to nurses on how
      they can help to establish more constructive relationships with these patients.

PMID- 8148247
TI  - Role extension: bendable or expendable?

PMID- 8148248
TI  - Community care: CPN'd of the line?

PMID- 8148249
TI  - The named nurse: a nurse with no name.

PMID- 8148250
TI  - The Standard guide to green nursing.

PMID- 8148251
TI  - Healthy platitudes.

PMID- 8148252
TI  - Computer reviews. Impressive presentations.

PMID- 8148253
TI  - Northern Ireland: a cautious road to reform.

PMID- 8148254
TI  - Clinical practice and management awards. The rewards of awards.

PMID- 8148255
TI  - Clinical developments in continence care.
AB  - In conjunction with National Continence Week, a joint initiative between the
      Department of Health and the Continence Foundation, this article reviews the
      development of continence care in this country and some of the key research
      projects which have influenced this development. The author also outlines the
      current research projects taking place and how these are likely to affect the
      future provision of services.

PMID- 8148256
TI  - Arterial leg ulcers (continuing education credit).

PMID- 8148258
TI  - Nom de gloom.

PMID- 8148257
TI  - Total parenteral nutrition (Part 2).
AB  - Last week, the author described the controversial history of total parenteral
      nutrition (TPN) and offered brief guidelines for safe and effective
      administration (1). She now concludes her overview of TPN by describing the
      metabolic, pharmacological, mechanical, infection control and psychological
      considerations which have such an important effect on the therapy.

PMID- 8148259
TI  - Childcare: poor start, poor finish.

PMID- 8148260
TI  - One minute wisdom. Trust efficiency induces bare bum trauma.

PMID- 8148261
TI  - Professional conduct: gift rapped.

PMID- 8148262
TI  - Research: cotton wool bull.

PMID- 8148263
TI  - Political correctness: dis-labelled rights.

PMID- 8148264
TI  - Complementary medicine. Viable alternative?

PMID- 8148265
TI  - Pay and conditions: 40 pieces of silver.

PMID- 8148266
TI  - The emerging epidemic of skin cancer.
AB  - A study of the incidence of skin cancer over a 14-year period in the North
      Humberside area of the U.K. indicates a steady rise in the numbers of the four
      most common types of skin cancer. A steep increase in the incidence of squamous
      cell carcinoma of the skin compared with that of internal squamous cell carcinoma
      was also detected. Our findings emphasize the need for continuing public
      education about both the dangers of UV radiation and measures to reduce exposure.

PMID- 8148267
TI  - Distribution and changing density of gamma-delta T cells in murine skin during
      the induced hair cycle.
AB  - Gamma-delta T cells (gdTC) are recognized as the predominant intraepidermal T
      cell population in murine skin, although their physiological functions are still
      unclear. Little is known of the exact distribution of gdTC in the other
      epithelial skin compartments of normal mice. Using selective gdTC-receptor
      antibodies in immunohistology (alkaline phosphatase technique), the distribution
      and density of gdTC was analysed morphometrically in cryostat sections of full
      thickness back skin of normal, adolescent C57 BL-6 mice in all the different
      stages of the depilation-induced hair cycle. We found that, during the entire
      hair cycle, V gamma 3-TCR-bearing lymphocytes are restricted to the epidermis,
      and to the epithelial hair bulb in, and distal to, the bulge area. No gdTC were
      seen in the sebaceous glands. During early anagen development, the number of pan
      gdTC receptor-positive cells increased significantly (P < 0.005) in the
      interfollicular epidermis and the suprainfundibular portion of the hair bulb,
      whereas the number decreased in the infrainfundibular region (P < 0.005). As gdTC
      are thought to migrate into the skin only during embryogenesis, this finding
      suggests hair cycle-dependent, differential intraepithelial proliferation of gdTC
      in murine skin. We advocate employing only skin of defined hair cycle stages in
      immunological studies on murine skin, and discuss the value of the C57 BL-6 model
      for assessing the functions of gdTC in skin and hair biology.

PMID- 8148268
TI  - Isolation and culture of follicular papillae from murine vibrissae: an
      introductory approach.
AB  - The recent successes in culturing follicular papilla cells have afforded a rapid
      advance in our understanding of hair biology. Although the experimental
      manipulation of the papilla is briefly described in the original reports, a
      detailed description for workers starting in the field is not yet available. In
      this report we give a brief review of hair biology relevant to the papilla, and
      illustrate the method we have found successful for isolating and growing papilla
      cells.

PMID- 8148269
TI  - Elevated phosphorylase kinase activity in psoriatic epidermis: correlation with
      increased phosphorylation and psoriatic activity.
AB  - To determine whether abnormal activity of a calmodulin-containing enzyme which
      catalyses phosphorylation reactions may play a pathogenetic role in psoriasis,
      the presence and activity of phosphorylase kinase (PK) in human epidermis were
      determined in patients with untreated/active psoriasis (n = 10),
      treated/resolving psoriasis (n = 10), and non-psoriatic controls (n = 10).
      Biopsies were taken from involved and uninvolved skin for PK, organic phosphorus,
      and inorganic phosphate estimation, and light and electron microscopy. The enzyme
      was present in involved and uninvolved skin of every patient in the study. PK
      activity (units/mg protein) was significantly higher in active psoriasis than in
      resolving psoriasis and controls. PK activity correlated directly with organic
      phosphorus levels, and inversely with the extent of cellular glycogenolysis
      measured by the depletion of glycogen granules within the keratinocytes. The
      study demonstrates that PK is present in both psoriatic and normal epidermis,
      with significantly higher levels in active psoriasis. Furthermore, higher levels
      of PK activity, glycogenolysis and phosphorylation are associated with increased
      clinical psoriatic activity. We conclude that PK, a calmodulin-containing enzyme,
      is involved in regulating calcium-dependent phosphorylation events in human
      epidermis, and disturbance of its activity may play a key role in the clinical
      manifestations of psoriasis.

PMID- 8148270
TI  - Epidermal Langerhans cells, HIV-1 infection and psoriasis.
AB  - Langerhans cells (LCs) subserve an important antigen-presenting function in the
      skin immune system. They bear CD4 receptors, which make them potential targets
      for infection with the human immunodeficiency virus (HIV-1). The observation of
      reduced numbers of LCs in the skin of patients with the acquired immunodeficiency
      syndrome (AIDS), and the association of severe psoriasis with HIV-1 infection,
      raise interesting questions regarding the role of LCs in the skin of HIV-1
      positive psoriatic patients. In this study, LCs were quantified in the lesional
      and non-lesional skin of seven HIV-1-positive psoriatic patients, and the results
      were compared with age-, sex- and site-matched HIV-1-negative psoriatic patients.
      The number of LCs was determined by staining skin sections with S-100 polyclonal
      antibody, using the three-step avidin-biotin immunoperoxidase method. The S-100
      positive cells above the basal layer were quantified in two ways: cells/mm2 of
      epidermal area, and cells/mm of length of basement membrane. HIV-1-positive
      psoriatic patients showed a reduction in the number of epidermal LCs compared
      with HIV-1-negative psoriatic patients using both methods of quantification, in
      both lesional and non-lesional skin (P < 0.05, Mann-Whitney test). In addition, a
      reduction in the number of LCs in lesional compared with non-lesional skin was
      observed in both HIV-1-positive and -negative patients when LCs were quantified
      per mm2 of epidermal area (P < 0.05, Wilcoxon test).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8148271
TI  - Cyclosporin A inhibits keratinocyte cytokine gene expression.
AB  - The immunosuppressive peptide cyclosporin A (CyA) is an extremely effective
      therapy for severe recalcitrant psoriasis, although its mechanism of action is
      unknown. In this study, we examined the effect of CyA on keratinocyte growth and
      cytokine expression, and showed that CyA inhibits the growth of murine and human
      keratinocytes (KC) and KC cell lines. In addition, CyA inhibits the expression of
      cytokine genes in a dose-dependent fashion. After 2 days' incubation with 20
      microM CyA, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), and
      interleukin 8 (IL-8) mRNA were decreased by 4-fold, 3.3-fold and 3.3-fold,
      respectively, in COLO-16, a keratinocyte cell line. IL-1 biological activity
      recovered from COLO-16 culture supernatants decreased to one-fifth of that of
      controls. In the murine KC cell line PAM 212, 10 microM CyA treatment for 2 days
      downregulated IL-1 alpha, tumour necrosis factor-alpha (TNF-alpha) and IL-1
      receptor by 60%, but had no effect on the message for interleukin 3 (IL-3),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), ornithine
      decarboxylase and beta-actin. Cells cultured for 5 days in the presence of CyA
      required much lower concentrations (2 microM) to achieve the same degree of
      inhibition of IL-1 alpha. Similar tissue concentrations of CyA have been reported
      in psoriatics undergoing CyA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148272
TI  - Stable and strong expression of basic fibroblast growth factor in naevus cell
      naevus contrasts with aberrant expression in melanoma.
AB  - It has been proposed that basic fibroblast growth factor (bFGF) is an autocrine
      growth factor of melanoma cells, in contrast with normal melanocytes where bFGF
      acts as a paracrine growth factor. As this notion is mostly based on the
      different requirements for bFGF in cultures of benign and malignant pigment cells
      in vitro, we performed an immunohistochemical study to examine bFGF expression in
      vivo, using paraffin sections from naevus cell naevi (NCN) and malignant melanoma
      (MM). All the NCN (n = 7) showed strong and homogeneous expression of bFGF
      protein, whereas the primary MMs (n = 5) showed heterogeneous expression, with a
      population of negative cells. Metastatic MMs (n = 5) also showed heterogeneous
      expression, and had a greater population of negative cells. These results suggest
      that bFGF has some, as yet unidentified, role in the growth of benign NCN, and
      that overexpression of bFGF is neither a prerequisite for melanoma genesis nor
      for progression to metastatic MM.

PMID- 8148273
TI  - Hydration, transepidermal water loss, pH and skin surface parameters:
      correlations and variations between dominant and non-dominant forearms.
AB  - The aim of this study was to examine differences between the skin of both
      forearms with regard to several parameters: hydration (skin capacitance),
      transepidermal water loss (TEWL), pH and skin surface parameters. Possible
      correlations between measurements were investigated. Thirty-three healthy women
      (32.6 +/- 8.4 years) participated in the study. The different parameters were
      measured on each volar forearm (dominant and non-dominant) at precisely
      delineated sites. TEWL and developed length (DL) were significantly increased on
      the dominant forearm (P < 0.001 and P < 0.01, respectively). In addition, a
      correlation matrix was calculated with the differences between dominant and non
      dominant forearms for all the parameters measured. Only the skin surface
      parameters were found to be interrelated with this statistical approach. These
      data confirm that randomization between forearms is essential in the design of a
      reliable experimental plan, and indicate the lack of relationship between these
      measurements as assessed in a group of healthy young women.

PMID- 8148274
TI  - Inhibition of erythromycin-resistant propionibacteria on the skin of acne
      patients by topical erythromycin with and without zinc.
AB  - Propionibacteria resistant to high concentrations of erythromycin [minimal
      inhibitory concentration (MIC) > or = 0.5 mg/ml] are now commonly isolated from
      the skin of antibiotic-treated acne patients. This double-blind study was carried
      out to assess the ability of 4% w/v erythromycin with and without 1.2% w/v zinc
      acetate to reduce the numbers of erythromycin-resistant propionibacteria in vivo,
      and also to monitor the acquisition of resistant strains de novo during therapy.
      Under laboratory conditions, erythromycin-resistant propionibacteria were shown
      to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the
      erythromycin/zinc complex and erythromycin alone produced highly significant
      reductions in total propionibacteria (P < 0.001) and in the number of
      erythromycin-resistant strains (P < 0.001 at 8 weeks). After 12 weeks, resistant
      propionibacteria were reacquired, or acquired de novo, by three patients treated
      with erythromycin alone and four patients treated with the erythromycin/zinc
      complex. In contrast, changes in numbers of Micrococcaceae were slight and, after
      12 weeks, erythromycin-resistant strains were predominant in both treatment
      groups. In vitro MIC determinations suggested that this finding might be
      explained by the exceptionally high degree of erythromycin resistance displayed
      by some staphylococcal strains (MIC > 4 mg/ml) and by the relative insensitivity
      of all staphylococcal strains to zinc acetate. Erythromycin with and without zinc
      was clinically effective, and both preparations produced significant reductions
      in acne grade, and inflamed and non-inflamed lesion counts (P < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8148275
TI  - Increased serum and blister fluid levels of creatine kinase in patients with
      toxic epidermal necrolysis.
AB  - Keratinocytes have recently been reported to contain creatine kinase (CK) of
      brain-type isoenzyme. The aim of this study was to investigate whether necrosis
      of keratinocytes induced raised CK levels in toxic epidermal necrolysis (TEN).
      The serum and blister fluid levels of creatine kinase and its isoenzymes
      [muscular-type (MM), brain-type (BB), myocardial-type (MB)] were measured in 40
      patients with TEN, 10 patients with other bullous dermatoses, and in suction
      blisters in five controls. The mean serum CK was significantly higher in TEN
      patients than in patients with other bullous dermatoses (mean +/- SD: 480 +/- 535
      U/l vs. 107 +/- 44 U/l, P < 0.05). The MM-isoenzyme was predominant (94%). A
      positive correlation was found between the level of the serum CK and the
      percentage of body surface area (BSA) involved (r = 0.49, P < 0.001). The mean
      blister CK was significantly higher in TEN patients than in patients with other
      bullous dermatoses or controls (mean +/- SD: 728 +/- 437 U/l vs. 310 +/- 244 U/l
      and 268 +/- 194 U/l, respectively, P < 0.02). The isoenzyme distribution of
      blister CK in TEN patients was: 76.8% MM, 18.1% MB and 5% BB. Although a
      significant part of blister CK comigrating with CK-MB, after preincubation with
      protein A-Sepharose, appeared to be CK-BB/IgG complex, the CK-BB fraction
      constituted less than 25% of blister CK. Therefore, the CK present in increased
      amounts in serum and blister fluid in TEN was not directly produced by
      keratinocytes.

PMID- 8148276
TI  - Neonatal lupus erythematosus. Report of serological and immunogenetic studies in
      twins discordant for congenital heart block.
AB  - Autoantibody, HLA studies and C4 phenotypes were performed on twins discordant
      for isolated congenital heart block. Serum from the mother and cord blood from
      the infants revealed Ro(SSA) and La(SSB) antibodies in all three sera. No
      significant difference in Ro(SSA) antibody titre was noted in the cord blood of
      either twin when compared with maternal titres, as detected by a sensitive ELISA
      assay. The infants' mother was HLA-DR3 positive. Both infants had identical HLA
      and C4 phenotypes. Immunoblot analysis revealed that sera from both mother and
      infants reacted with the 52-kDa Ro(SSA) macromolecule. Quantitative cord blood
      IgM levels were not elevated in either twin. This study indicates that placental
      transfer of anti-Ro(SSA) or anti-La(SSB) alone to the fetus is not sufficient for
      the expression of congenital complete heart block. We conclude from this
      experiment of Nature that there must be a second event determining which infant
      develops complete heart block, but this is unknown at present.

PMID- 8148277
TI  - Surface microscopy of naevi and melanomas--clues to melanoma.
AB  - In this present study, 260 histologically confirmed melanocytic skin tumours (188
      benign naevi and 72 malignant melanomas; from 1989 to 1990) were investigated
      with regard to valid surface microscopical criteria of malignancy. The tumours
      were analysed using a system which assessed eight components. Most melanomas were
      characterized by the following pattern: asymmetrical pigment distribution, more
      than three colours, black pigment, peripheral stripes, and asymmetrical
      depigmentation. The results were evaluated statistically by contingency tables
      and logistic regression procedures. On the basis of the classification derived,
      the sensitivity and specificity were determined for lesions from 1991, and were
      0.9 and 0.85, respectively. Many melanocytic naevi were not identified by the
      above criteria, or were found only occasionally. Pigment network was often absent
      in naevi and melanomas, and was not decisive for the diagnosis. The present
      investigation demonstrates that in vivo diagnosis of pigmented melanocytic
      lesions can be improved by surface microscopy.

PMID- 8148278
TI  - Differences in phototoxic potency should be considered when tetracyclines are
      prescribed during summer-time. A study on doxycycline and lymecycline in human
      volunteers, using an objective method for recording erythema.
AB  - In order to test the phototoxic potency of the two tetracyclines most frequently
      prescribed in Sweden, a double-blind cross-over study using a double-dummy
      technique with doxycycline 0.1 g twice daily, lymecycline 0.6 g twice daily, and
      placebo, was performed in 15 healthy volunteers. Drugs were given for 3
      consecutive days, and on the third day volunteers were tested with 25, 50, 75 and
      100 J/cm2 of artificial long-wave ultraviolet radiation (UVA), and assessed 6 h
      later for erythematous photoreactions. Objective readings were made using skin
      reflectance spectrophotometry. All three substances were tested in each
      individual at weekly intervals. Within 50, 75 and 100 J/cm2 of UVA, lymecycline
      showed a slight increase in erythema compared with placebo, but this was not
      significant (50 and 100 J/cm2), or was of low significance (75 J/cm2). However,
      with the same doses, doxycycline showed a substantial increase in erythema
      compared with placebo, which was highly significant. We conclude that doxycycline
      has a higher phototoxic potency than lymecycline, and this is in agreement with
      earlier in vitro experimental data. We recommend that therapy with doxycycline is
      avoided during summer-time, and during holidays in a sunny climate.

PMID- 8148279
TI  - Photoprotective action of emollients in ultraviolet therapy of psoriasis.
AB  - An in vitro technique was used to measure the monochromatic protection factors of
      all emollients available on prescription. The action spectra for ultraviolet
      erythema and erythema in psoralen-sensitized skin were used to calculate, for
      each emollient, erythema protection factors relevant to UVB phototherapy and
      psoralen photochemotherapy, respectively. Of the 40 products tested, 22 (55%) had
      a UVB erythema protection factor > 1.2 at an application density of 2
      microliters/cm2, and 31 (78%) at an application density of 4 microliters/cm2.
      Fewer products, 25% at 2 microliters/cm2 and 50% at 4 microliters/cm2, had a
      psoralen erythema protection factor > 1.2. A protection factor of 1.2 is
      equivalent to a reduction in ultraviolet dose of 17%, and is thus likely to be of
      clinical importance. These results allow a choice of emollient products which may
      improve response by increasing transmission of radiation through psoriasis scale
      without a concomitant decrease in transmission due to a sunscreening action.

PMID- 8148281
TI  - Maintenance treatment with cyclosporin in atopic eczema.
AB  - We have studied two reducing-dose regimens intended to minimize toxicity of
      cyclosporin A (CyA) while maintaining its capacity to control atopic eczema
      following induction of remission. Twenty-four patients with severe chronic atopic
      eczema were first treated in a double-blind randomized placebo-controlled cross
      over study of CyA (5 mg/kg/day). All 19 who completed the study showed the
      expected highly significant improvements, compared with placebo, in area
      involved, erythema, excoriation, lichenification, itch and requirement for
      topical steroid. In 17 of the 19 patients, control was re-established with CyA 5
      mg/kg/day, and they were then re-randomized to stepwise reduction at 2-week
      intervals in either (i) the dose of CyA given daily, or (ii) the frequency with
      which the 5 mg/kg dose was given. Fifteen patients (seven continuous reducing
      dose, eight intermittent fixed dose) completed the planned reduction to either 1
      mg/kg/day or 5 mg/kg every fifth day. In both groups the response was sustained
      despite dose reduction, although control was less good at a continuous dose of 1
      mg/kg. Intermittent treatment was as good as or better than continuous reducing
      dosage in this study, and in both groups there was further deterioration after
      the drug was stopped. The findings suggest that the dose of CyA required to
      control atopic eczema is less than that required to achieve remission, and that
      the therapeutic index can be further improved by alternative dosing strategies.
      This offers a new approach to maintenance treatment of eczema and other chronic
      refractory dermatoses.

PMID- 8148280
TI  - Efficacy and safety of oral cyclosporin A (CyA; Sandimmun) for long-term
      treatment of chronic severe plaque psoriasis.
AB  - The value of oral cyclosporin A (CyA; Sandimmun) in the treatment of chronic
      severe plaque psoriasis has already been established. Many controlled studies
      have addressed the issues of efficacy and safety, mostly in studies of several
      months duration. Patients treated for up to several years have been reported, but
      never in multicentre controlled studies. Guidelines have established the maximum
      dose permissible to reduce the risk of side-effects. However, the efficacy and
      safety of therapy of longer duration remain under investigation. The results of a
      multicentre prospective randomized clinical study (251 patients) to evaluate the
      efficacy, safety and tolerability of two dose levels of CyA (2.5 or 5 mg/kg/day)
      for inducing remission, and for use in long-term maintenance therapy for up to 21
      months, are presented. An assessment of relapse as the dose was tapered (during
      the last 3 months of treatment), and the reversibility of CyA-induced side
      effects, is also presented (follow-up phase of 3 months). Efficacy was evaluated
      by means of the psoriasis area and severity index (PASI). Safety was assessed by
      using the results of vital signs, physical examination, laboratory tests and
      physician and patient evaluation of adverse events. During the induction of
      remission phase of therapy, a total of 184 patients (73%) were treated
      successfully. The percentage of patients classified as successes at the end-point
      was significantly higher in the group on 5.0 mg/kg/day (92%) than in that on 2.5
      mg/kg/day (52%; P < 0.001). A total of 215 (86%) patients reported at least one
      adverse event during the study. In 136 patients (54%) the reported adverse event
      was judged by the investigator as being related to CyA. Nineteen patients (8%)
      reported events that were judged as severe, and related to treatment with CyA. A
      total of 45 patients (18%) discontinued treatment due to adverse events.
      Hypertension was one of the reasons, or the reason, for discontinuation in 16
      patients (6%). The occurrence of hypertension appeared unrelated to CyA dose. One
      hundred and sixteen patients (46%) experienced a maximum increase in serum
      creatinine > 30% above baseline values on at least one occasion. This increase in
      serum creatinine was often transient, and was one of the reasons, or the reason,
      for discontinuation in 24 patients (10%). An increase in serum creatinine > 30%
      above baseline was dose-related. The results of this study show that 5.0
      mg/kg/day of CyA is significantly more effective than 2.5 mg/kg/day in the
      treatment of chronic plaque psoriasis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8148282
TI  - Protein S deficiency in lupus erythematosus secondary to hereditary angio-oedema.
AB  - We report a child with lupus erythematosus secondary to type 2 hereditary angio
      oedema (HAE). Reduced levels of free protein S were found. Total protein S, and
      C4 binding protein (C4bp) were normal, and there was no evidence of
      anticardiolipin antibodies or lupus anticoagulant. We postulate that reduced
      levels of C4, secondary to C1 inhibitor deficiency, resulted in increased binding
      of protein S to C4bp, leading to reduced levels of free protein S and thus
      functional deficiency of protein S.

PMID- 8148283
TI  - Systemic lupus erythematosus in association with ulcerative colitis: related
      autoimmune diseases.
AB  - We report a patient who developed urticaria, angio-oedema and polyarthropathy
      secondary to the hypocomplementaemic urticarial vasculitis syndrome, a year prior
      to the onset of ulcerative colitis. Ten years later, primary sclerosing
      cholangitis and the antiphospholipid syndrome developed concomitantly. We believe
      this patient represents only the second reported case of idiopathic systemic
      lupus erythematosus (SLE) occurring in association with ulcerative colitis.

PMID- 8148284
TI  - Partial unilateral lentiginosis associated with blue naevi.
AB  - We report a patient with unilateral lentiginosis and blue naevi. This association
      has not been reported previously. Additional clinical features included right
      bundle branch block and lateral popliteal nerve palsy.

PMID- 8148285
TI  - Electron-beam therapy in scleredema adultorum with associated monoclonal
      hypergammaglobulinaemia.
AB  - We report a case of scleredema adultorum (Buschke's disease) associated with an
      IgA kappa monoclonal hypergammaglobulinaemia. A significant improvement in the
      skin was obtained with electron-beam therapy. Scleredema would appear to be
      linked to monoclonal hypergammaglobulinaemia, but the relationship between the
      skin disorder and the immunoglobulin abnormality remains to be elucidated.

PMID- 8148286
TI  - Pyoderma gangrenosum and subcorneal pustular dermatosis, without monoclonal
      gammopathy.

PMID- 8148287
TI  - Subungual hair implantation in hairdressers.

PMID- 8148288
TI  - Cetirizine may block transmigration of eosinophils at post-capillary venules.

PMID- 8148289
TI  - Brachial plexus block. A comparison of the supraclavicular lateral paravascular
      and axillary approaches.
AB  - BACKGROUND AND OBJECTIVES: Anesthesia of the brachial plexus has been associated
      with injuries to adjacent structures (e.g., pneumothorax, vascular penetration).
      It is not uncommon to have only partial block of the upper extremity, hindering
      completion of the surgical procedure. The supraclavicular lateral paravascular
      approach to brachial plexus anesthesia has been proposed as an effective, safe
      alternative to the traditional approaches to brachial plexus anesthesia. METHODS:
      This prospective, randomized study sought to determine if the supraclavicular
      lateral paravascular (SCLP) approach is as effective as the transarterial
      axillary approach, the most common brachial plexus block used at our institution.
      RESULTS: 16/20 (80%) of SCLP blocks were good. 13/20 axillary blocks were good.
      The success rate with the SCLP approach was 95%. The success rate with the
      axillary approach was 90%. CONCLUSIONS: The supraclavicular lateral paravascular
      approach is as effective as the axillary approach.

PMID- 8148290
TI  - Sensory, motor, and sympathetic block during epidural analgesia with 0.5% and
      0.75% ropivacaine with and without epinephrine.
AB  - BACKGROUND AND OBJECTIVES: Ropivacaine is a new long-acting local anesthetic,
      with vasoconstrictive properties. The purpose of this randomized, double-blind
      study was to evaluate sensory, motor, and sympathetic block following epidural
      anesthesia, and the influence of the addition of epinephrine. METHODS: Forty
      eight male patients, scheduled for transurethral surgery, received 20 mL of 0.5%
      or 0.75% ropivacaine with or without addition of epinephrine (5 micrograms/mL)
      epidurally. Sensory block was assessed by pinprick, motor block by a modified
      Bromage scale, and sympathetic block by skin resistance level, skin resistance
      response, skin temperature, and skin blood flow (laser Doppler flowmetry).
      RESULTS: Onset time for analgesia was short (Th10 blocked after median 5.3-6.7
      minutes), and maximum segmental level was median Th 2-3 (range, Th5-C4). A
      tendency toward a dose-response relationship (duration of sensory block) was
      noted for the 0.75% solutions (median, 258-264 minutes at Th10) compared to the
      0.5% solutions (median, 228-234 minutes at Th10). Only about half of the patients
      exhibited a complete motor block of the lower extremities with a longer duration
      with the 0.75% solutions. The majority of patients had a marked or complete
      sympathetic block in the lower limbs. Short-lasting, mild hypotension, responding
      well to ephedrine intravenously, was noted in 40%-70% of the patients. No serious
      adverse reactions were observed. CONCLUSIONS: Ropivacaine given epidurally
      provided adequate sensory anesthesia and motor block for transurethral surgery.
      Addition of epinephrine did not provide any significant prolongation of the
      sensory or motor block, nor any influence upon the sympathetic block.

PMID- 8148291
TI  - Subarachnoid morphine and fentanyl for labor analgesia. Efficacy and adverse
      effects.
AB  - BACKGROUND AND OBJECTIVES: The study was designed to compare analgesic efficacy
      and associated adverse effects between a group of parturients receiving
      subarachnoid opioids via the combined spinal-epidural (CSE) technique with a
      group receiving epidural analgesia alone for labor. METHODS: The authors studied
      59 healthy parturients admitted for labor and delivery. Group 1 consisted of 26
      consecutive patients who received the CSE technique, initially receiving
      subarachnoid morphine sulfate 0.25 mg, and fentanyl 25 micrograms, for labor
      analgesia. If patients requested additional analgesia, epidural analgesia was
      initiated. Group 2 was comprised of 33 consecutive patients who received
      conventional epidural analgesia. All patients were monitored for the occurrence
      and treatment of peripartum nausea and vomiting (N/V), pruritus, postdural
      puncture headache, and respiratory depression. RESULTS: Additional analgesia was
      requested by 20/26 (76%) patients in group 1. Group 1 reported more N/V (50%
      versus 15%, P = .01) and required more therapy for N/V (31% versus 0%, P < .01)
      than group 2. Furthermore, group 1 reported having more pruritus (50% versus 3%,
      P < .01), and required more treatment for pruritus (35% versus 3%, P < .01), than
      group 2. No patient developed significant respiratory depression. Only one
      patient in group 1 developed a postdural puncture headache, following
      unintentional dural puncture with the 18 gauge Tuohy needle. CONCLUSIONS: The
      combination of subarachnoid morphine 0.25 mg and fentanyl 25 micrograms, when
      used for labor analgesia as part of the CSE technique, was associated with a
      higher incidence of clinically significant nausea and vomiting and pruritus,
      compared to conventional epidural anesthesia. Furthermore, the combination of
      subarachnoid morphine and fentanyl proved ineffective in providing adequate pain
      relief for the duration of labor and delivery for the majority of patients. The
      authors recommend that subarachnoid morphine and fentanyl serve a limited role in
      the treatment of labor pain.

PMID- 8148292
TI  - Comparative flow rates of saline in commonly used spinal needles including pencil
      tip needles.
AB  - BACKGROUND AND OBJECTIVES: Certain characteristics of spinal needles that can
      influence their clinical usefulness were examined, namely, flow rates, internal
      diameters, and size of orifices of pencil-type needles. METHODS: Flow rates of
      0.9% sodium chloride solution were measured in spinal needles with an infusion
      pressure of 10 mmHg at isothermic and steady-state conditions. In 15 different
      types, a new needle was used for each experiment, and 6 experiments were
      performed with each needle type for a total of 90 experiments. The Hagen
      Poisseuille Law for laminar flow was used to calculate the internal diameters.
      RESULTS: The flow rates of needles of the same gauge varied considerably
      depending on the manufacturer. Compared with 26-gauge ultrathin-wall spinal
      needle produced by the same manufacturer (Braun, Bethlehem, Pennsylvania), the
      flow rate through 29-gauge spinal needle was 18% that of the former needle. The
      flow rate through 27-gauge Quincke Whitacre needle (Becton Dickinson, Rutherford,
      New Jersey) was not statistically different from that through 26-gauge needle by
      the same manufacturer. By arbitrarily choosing < or = 2 seconds to be the in
      vitro desirable period for saline to traverse the needle from one end to the
      other, all needles with the exception of 29-gauge and standard 26-gauge Quincke
      Braun needles met this criterion. The length and size of the orifices of Whitacre
      needles were found to be significantly smaller than those of Sprotte needles
      (Havel, Cincinnati, Ohio). The orifice of Sprotte needle was longer than the
      known thickness of the dura while that of the Whitacre needle was smaller.
      CONCLUSIONS: Needles of the same gauge do not necessarily have the same flow
      rate. Flow rate correlates well with internal, not external, diameter. By
      considering < or = 2 seconds to be the desirable time for saline to traverse a
      spinal needle, all, except two, meet this criterion. The orifice of Whitacre
      needle has more desirable features than that of Sprottle needle.
      Anesthesiologists are encouraged to use 27-gauge needles since their flow rate is
      not slower than that of 26-gauge needles.

PMID- 8148293
TI  - Do agents used for epidural analgesia have antimicrobial properties?
AB  - BACKGROUND AND OBJECTIVES: Local anesthetics inhibit bacteria growth in culture
      although this effect diminishes as the concentration of the drug is reduced. The
      antimicrobial properties of opioids are unknown. This study was designed to
      determine the ability of lidocaine and bupivacaine, with or without fentanyl or
      sufentanil, to inhibit bacteria growth in culture at concentrations typically
      used to provide analgesia. METHODS: Potential bacteria pathogens were cultured in
      agar media containing: agar alone, 2%, 1.5%, and 1% lidocaine, 0.5%, 0.25%, and
      0.125% bupivacaine, 0.125% bupivacaine + fentanyl 2 mcgs/mL, 0.125% bupivacaine +
      sufentanil 0.3 mcgs/mL, and fentanyl 5 mcgs/mL, fentanyl 2 mcgs/mL or sufentanil
      0.3 mcgs/mL. Organisms were deemed sensitive to the study agent if no growth was
      apparent after incubation for 24 hours. RESULTS: Both lidocaine and bupivacaine
      significantly reduced bacteria growth at all concentrations studied compared to
      the growth observed in agar alone (P < .0001). This growth inhibition diminished
      as the concentration of local anesthetic was reduced especially for certain
      bacteria species for example. Staphylococcus aureus (P < .0001). Neither fentanyl
      nor sufentanil inhibited any bacterial growth in culture. CONCLUSIONS: Since the
      growth in culture of common pathogens, especially S. aureus, is not inhibited as
      the concentration of local anesthetic is reduced, the local anesthetics tested
      are unlikely to help prevent epidural-catheter-related infection due to common
      pathogens. More study is necessary to determine if local anesthetics help prevent
      infection from less common pathogens in patients at increased risk for infectious
      complications.

PMID- 8148294
TI  - Diluting lidocaine and mepivacaine in balanced salt solution reduces the pain of
      intradermal injection.
AB  - BACKGROUND AND OBJECTIVES: Intradermal injection of local anesthetics prior to
      percutaneous needle insertion is often painful. This study evaluated the effect
      of diluting lidocaine and mepivacaine with balanced salt solution on perception
      of pain on intradermal injection. METHODS: Twenty healthy volunteers were each
      intradermally injected with six solutions in random order. These solutions were:
      normal saline (NS), 0.9% benzyl alcohol in NS, 0.2% lidocaine in NS, 0.2%
      lidocaine in balanced salt solution, 0.2% mepivacaine in NS, and 0.2% mepivacaine
      in balanced salt solution. Discomfort of each injection was reported on a 0-2
      pain scale. The degree of anesthesia at each site was evaluated by pinprick every
      minute for 20 minutes. RESULTS: Benzyl alcohol and lidocaine and mepivacaine in
      balanced salt solution caused the least injection pain. However, mepivacaine in
      NS and NS alone caused the most pain. The anesthetic effect of benzyl alcohol was
      judged adequate for only 4 minutes whereas both lidocaine and mepivacaine in
      either NS or balanced salt solution gave adequate anesthesia for at least 15
      minutes. CONCLUSIONS: The dilution of lidocaine and mepivacaine with balanced
      salt solution produces a solution that is both painless on injection and of
      moderate duration.

PMID- 8148295
TI  - Effects of epidural test dose volume on skin perfusion, temperature, and reflex
      vasoconstriction.
AB  - BACKGROUND AND OBJECTIVES: The authors sought to define the effects of differing
      volumes of epidural test dose on skin perfusion, skin temperature, and reflex
      vasoconstriction to a maximal inspiration (inspiratory gasp vasoconstrictive
      response, IGVR). METHODS: With informed consent and Institutional Review Board
      approval, the authors studied 40 patients undergoing epidural anesthesia. Skin
      perfusion was monitored in glabrous skin on the foot using laser Doppler.
      Inspiratory gasp vasoconstrictive response and temperature measurements were
      obtained at 1-minute intervals. After a baseline period, 5 patients received 60
      mg intravenous lidocaine HCl; 5 received 5 mL normal saline, via epidural
      catheter; and 30 patients received 50 mg lidocaine HCl and 20 mcg epinephrine in
      2.5, 5.0, or 7.5 mL normal saline (10 patients each). Inspiratory gasp
      vasoconstrictive response was defined as the percent change in perfusion from
      baseline produced by an inspiratory gasp. Perfusion was normalized by expressing
      each patient's value as a percentage of the respective baseline value. RESULTS:
      Significant increases in perfusion, of up to 169% of baseline, were seen 12
      minutes after the test dose. Inspiratory gasp vasoconstrictive response showed
      significant changes from baseline in all test groups. The temperature change was
      insignificant. Control groups did not show perfusion or IGVR changes.
      CONCLUSIONS: Skin perfusion and IGVR changed significantly after epidural test
      dose; the minimal effect of volume appears to be 5 mL of lidocaine-epinephrine
      solution; the presence of IGVR or perfusion changes, or both, are positive
      predictors of successful placement of the catheter into the epidural space; and
      temperature changes as observed here were not reliable predictors of proper
      placement of epidural catheters.

PMID- 8148296
TI  - Blister formation on the thumb following the second intravenous regional
      reserpine in the hand. Case report.
AB  - BACKGROUND AND OBJECTIVES: Local, not systemic, complications associated with
      intravenous regional sympathetic block (IVRS) are very rare. The authors report
      the complication that occurred in a 70-year-old man who sustained an injury of
      the left thumb. METHODS: The second IVRS using reserpine and lidocaine, 1 week
      after the first IVRS, was performed for pain relief. RESULTS: About 1 hour after
      the operation, an entirely localized blister developed in the dorsolateral aspect
      of the thumb. The palmar side appeared viable 2 weeks after the operation, which
      guaranteed intact survival of the thumb, but 2 months later the patient reported
      that he had the thumb amputated at an outside hospital. CONCLUSIONS: When IVRS is
      applied to the extremities with compromised vasculature, or with an altered
      neuroanatomy, unpredictable and counterproductive mishaps may occur.

PMID- 8148297
TI  - Postblock epidural hematoma causing paraplegia. Case report.
AB  - BACKGROUND AND OBJECTIVES: An elderly man with no obvious preexisting coagulation
      disorder had paraplegia following epidural block for transurethral prostatectomy
      that was later found to be due to a large epidural hematoma requiring surgical
      decompression of the spinal cord. METHODS: There was a delay in starting
      treatment since the cause was not initially suspected. RESULTS: The patient did
      not improve much after the operation. CONCLUSIONS: The anesthesiologist should be
      alert to the possibility of epidural hematoma forming in otherwise normal
      patients to avoid such unfavorable outcomes.

PMID- 8148298
TI  - Multiple epidural abscesses and spinal anesthesia in a diabetic patient. Case
      report.
AB  - BACKGROUND AND OBJECTIVES: Spinal anesthesia as a cause of epidural abscess is
      extremely rare. Infection at the site of needle placement is the usual cause of
      abscess formation. METHODS: Immunocompromised patients, and in this case a
      diabetic patient may be at higher risk for this complication. RESULTS:
      Anesthesiologist need to be aware of factors that may lead to epidural abscess
      formation. CONCLUSIONS: The signs and symptoms of this unfortunate complication
      should be uppermost in the physician's mind when assessing new neurologic
      deficits after regional anesthesia.

PMID- 8148299
TI  - Combined spinal and epidural anesthesia for abdominal hysterectomy in a patient
      with myotonic dystrophy. Case report.
AB  - BACKGROUND AND OBJECTIVES: The authors report a case of myotonic dystrophy in a
      34-year-old woman who presented for total abdominal hysterectomy. The goal of
      anesthetic management is to prevent the known triggers of myotonic crisis, such
      as hypothermia, shivering, and hyperkalemia; and to avoid depolarizing muscle
      relaxants and anticholinesterase agents. METHODS: In this patient, the authors
      used combined spinal and epidural block for intraoperative anesthesia and
      postoperative analgesia. RESULTS: The advantages of the combined technique offers
      rapid onset and good muscle relaxation from subarachnoid block, with the ability
      to supplement analgesia through the epidural catheter both during and after
      surgery. In addition, the potential complications associated with general
      anesthesia, including respiratory insufficiency, aspiration pneumonia, cardiac
      arrhythmia, and heart failure can be avoided. The other measures were directed
      toward the prevention of shivering, a common problem encountered with general or
      regional anesthesia. CONCLUSIONS: After the postoperation, optimal analgesia was
      obtained by infusing local anesthetic (0.125% bupivacaine) via the epidural
      catheter. No obvious side effects occurred. The authors believe combined spinal
      and epidural block provides a safe alternative, to other techniques, and
      minimizes the potential hazards of myotonic dystrophy, while offering effective
      intraoperative anesthesia and postoperative analgesia.

PMID- 8148300
TI  - Concomitant use of epidural opioids and antiemetics?

PMID- 8148301
TI  - Continuous interscalene block for cancer pain.

PMID- 8148302
TI  - Eutetic mixture of local anesthetics: not just for kids.

PMID- 8148303
TI  - Sciatic nerve block. A comparison of single versus double injection technique.
AB  - BACKGROUND AND OBJECTIVES: Two techniques, single versus double injection, for
      blocking the sciatic nerve via the classical (Labat) approach were prospectively
      evaluated for onset and efficacy of block in 50 adult patients undergoing lower
      extremity surgery. The tibial, common peroneal, and posterior femoral cutaneous
      nerves were evaluated at 5, 10, 15, 20, 30, and 45 minutes after the initial
      injection of local anesthetic. Motor function was used to assess the block of the
      tibial and common peroneal nerves while pinprick response was used to assess
      block of the posterior femoral cutaneous nerve. METHODS: Group 1 (n = 25)
      received a single injection of 20 mL of an amide-ester solution (1%
      lidocaine/0.2% tetracaine) with epinephrine 1:200,000 when either component of
      the sciatic nerve (tibial or peroneal) was identified with the aid of a
      peripheral nerve stimulator. Group 2 (n = 25) received two 10 mL injections of
      the same solution with the tibial and peroneal components of the sciatic nerve
      being identified and injected separately (through the same skin wheal in serial
      fashion by withdrawing and redirecting the needle). The two groups were compared
      at each of the time intervals with analysis of variance. RESULTS: Group 2 (double
      injection) showed faster onset and better efficacy (P < .05) at all time
      intervals evaluated. CONCLUSIONS: The double injection technique for sciatic
      nerve block via the classical approach results in a more rapid onset and
      increased efficacy of block than that of the single injection technique.

PMID- 8148304
TI  - [Superoxide-generating system in leukocytes: its activation mechanism and
      significance].
AB  - Leukocytes such as neutrophils, eosinophils, monocytes and B lymphocytes but not
      T lymphocytes nor NK cells have a special electron transport system on their
      plasma membrane and generate superoxide anion upon stimulation. Superoxide anion
      is released to the outside of the cells (or inside of phagosomes if they are
      phagocytes), where other active oxygen species are formed secondarily. These
      species may be used for killing infectious agents. Superoxide-generating system
      in these cells consists of a total of 5 proteins, i.e. 91- and 22-kDa subunits of
      cytochrome b558 in membrane and 21-, 47- and 65-kDa proteins in cytoplasm. Upon
      stimulation, a functionally active complex is formed in the membrane, which
      caries electrons from NADPH in the cytoplasm to molecular oxygen at the surface
      of the cells. Any defect in these components except the cytosolic 21-kDa protein
      (a small GTP binding protein, Rac) causes chronic granulomatous disease, an
      inherited disorder where leukocytes can not generate superoxide anion. The
      patients with this disease suffer from recurrent, life-threatening infections of
      catalase-positive microorganisms. This review will focus on active oxygen species
      formed during phagocytosis, components of superoxide-generating system in
      neutrophil and B lymphocytes, its activation mechanism and significance of active
      oxygen formation by the cells.

PMID- 8148305
TI  - Immortalization of normal human cells is a multistep process and a rate limiting
      step of neoplastic transformation of the cells.
AB  - Three normal human fibroblast strains were immortalized by treatment with either
      4-nitroquinoline 1-oxide (SUSM-1 and OUMS-24F lines) or 60Co gamma rays (KMST-6
      line). Immortalization of normal human cells with these agents required repeated
      treatments. Before immortalization, most of the cells treated with these
      mutagenic agents showed more or less chromosome aberrations, but immortalized
      cells appeared very rarely. This suggests that several mutational events are
      involved in the immortalization process itself. The immortalized cells showed
      polygonal or epithelial-like morphology, prominent numerical and structural
      abnormalities of chromosomes, requirement of serum growth factors for their
      growth, and no tumorigenicity. The immortalized KMST-6 and OUMS-24F were further
      transformed into neoplastic ones by the ras oncogene, but not by transfection
      with the mutant p53 gene. Normal human fibroblasts which are mortal were not
      immortalized nor neoplastically transformed with the ras oncogene or the mutant
      p53. These findings strongly indicate that the immortalization of human cells is
      prerequisite for neoplastic transformation of the cells.

PMID- 8148306
TI  - [Role of the RB gene in carcinogenesis].
AB  - RB protein is an intranuclear phosphoprotein encoded by the RB gene which was
      isolated as a human tumor suppressor gene from the 13q14 locus. One of the
      important functions of the RB protein is to regulate cell cycle by interacting
      with a variety of molecules. Biological analysis of the RB protein at the
      cellular level has been performed by either transfecting a wild-type RB gene into
      RB-mutated cancer cells or knocking out the endogenous RB gene in transgenic
      mouse experiments. Role of the RB gene in multistep carcinogenesis and its
      additional aspects, including the regulation of cell surface adhesion or invasion
      related phenotypes, have also been elucidated.

PMID- 8148307
TI  - [Mechanism of transcriptional activation by HTLV-1 Tax].
AB  - A trans-activator protein Tax of HTLV-1 activates the transcription of various
      cellular genes as well as viral promoter through the multiple enhancer elements
      and leads cells to the transformation. Tax protein interacts to enhancer DNA
      elements by associating with cellular enhancer binding proteins such as CREB, NF
      kappa B and SRF. In addition, we found recently that Tax interacts with an I
      kappa B protein, the inhibitor of NF-kappa B, resulting in the enhancement of
      nuclear translocation of NF-kappa B molecules. Therefore, Tax seems to modulate
      the transcription by the interaction with multiple transcription factors in
      different modes of control.

PMID- 8148308
TI  - [Leukemia and nuclear proteins].
AB  - Recently, lot of evidences are showing that the expression of some subsets of
      genes are essential for leukemogenesis. It becomes clear that nuclear proteins
      namely transcription factors-have important roles for the development of
      leukemias from the studies of avian virus-induced leukemia, murine leukemia
      models of transgenic mice, and chromosome translocations of human leukemias. In
      this review article, some transcription factors involved in leukemogenesis are
      chosen and their roles in leukemogenesis are explained.

PMID- 8148309
TI  - [Establishment and characterization of a CA125-producing human ovarian clear cell
      carcinoma cell line].
AB  - A human ovarian cancer cell line designated "KK" was established from ascites of
      a patient with ovarian clear cell carcinoma. This cell line was grown for more
      than 2 years and over 140 passages in medium RPMI1640 containing 10% FCS.
      Doubling time of this cell line at passage 70 was approximately 4 days and
      saturation density was 1.1 x 10(5)/cm2. Plating efficiency was approximately 23%.
      Chromosome analysis revealed aneuploidy with a model number of 67. PAS-positive
      substances were present in the cytoplasm. CA125 and SLX were detected in both the
      original tumor and the cultured cells. This cell line is less sensitive to
      cisplatin than KF cells and IC50 was 0.95 microM.

PMID- 8148310
TI  - Tungsten modulates the toxicity of paraquat for epithelial cells.
AB  - The modulation of paraquat toxicity by tungsten was studied in vitro using
      cultured MDCK epithelial cells. MDCK cells were cultured in minimal essential
      medium with or without 1 ppm tungsten. Proliferation of cells cultured with
      tungsten was not inhibited after exposure to 0.25 mM or 0.5 mM paraquat. In
      addition, lactate dehydrogenase release into the culture medium was lower for
      tungsten-treated cells than for cells cultured without tungsten. Cells cultured
      in medium alone showed reduced viability compared with controls after exposure to
      0.5 mM paraquat, but 0.25 mM paraquat did not decrease cell viability. Tungsten
      treated cells showed no decrease viability in after exposure to either
      concentration of paraquat. Cells exposed to paraquat developed a honeycomb
      morphology with scanty cytoplasm and abnormal nucleoli. However, these major
      structural changes were not observed in cells cultured with tungsten. Our study
      showed that cell damage after paraquat exposure was modulated by addition of
      tungsten to the culture medium. It is suggested that cytosolic xanthine oxidase
      activity was reduced by tungsten, leading to less production of superoxide and
      other radicals and thus conferring resistance to paraquat toxicity.

PMID- 8148311
TI  - Establishment of a neuroblastoma cell line and induction of lymphokine-activated
      killer (LAK) activity against the autologous neuroblastoma cell line.
AB  - We have established a new human neuroblastoma (NB) cell line from the bone marrow
      of a 1-year-old boy with NB, termed JK-NB1, which showed constant growth for as
      long as 17 months or more, similar phenotype to those of other reported NB cell
      lines, colony formation in liquid and methylcellulose culture, N-myc
      amplification, high expression of N-CAM, and NSE production. We have tried to
      induce LAK cell activity with peripheral blood mononuclear cells (PBMCs) from the
      patient against the autochthonous JK-NB cells. PBMCs from the patient
      proliferated up to 20-fold in the presence of interleukin-2 (IL-2) after 9 days
      of incubation, and LAK activity increased up to 24.7-fold and killed all of the
      JK-NB1 cells. In contrast, IL-2 alone or PBMCs from the patient or a healthy
      adult donor had little effect on the growth of NB cells. These data suggest that
      it is possible to induce LAK cell activity in PBMCs from the patient against
      autologous as well as allogenic NB cells, and provide a rational base for the
      clinical use of IL-2 as one of the treatments for NB.

PMID- 8148312
TI  - Chemotactic response of fibroblasts to root surface components in wound healing
      following flap surgery.
AB  - The purpose of this study was two-fold; first to investigate the chemotactic
      response of periodontal cells to root surface components during wound healing
      following flap surgery; second, to investigate the chemoattractive effect of the
      root components on cell migration. Cells were obtained by culturing cells from
      monkey periodontal tissues and rat calvarial cells. Root surface components were
      obtained from teeth extracted at 4, 7, 10 and 14 days after flap surgery. The
      chemotactic response of the isolated cells to root surface components was
      quantitated by an in vitro assay using a 48 well microchemotaxis chamber. The
      effect of root components or other growth factors on the cell migration was
      evaluated using a three-dimensional gel system. Cemental components produced a
      strong chemotactic response for gingival fibroblasts, alveolar bone cells and rat
      calvarial cells. Kinetics of the chemotactic potential of cementum was
      characterized by an initial increase (up to 7 days after surgery), a transient
      decline (at 10 days after surgery) and a second increase (at 14 days after
      surgery). Cemental components obtained 7 days after surgery most profoundly
      facilitated invasion of gingival fibroblasts with comparable effects induced by
      PDGF and TGF-beta. These results suggest that cemental components influence the
      chemotactic migration of gingival fibroblasts at the initial stage of wound
      healing, and therefore, cementum plays an important role in periodontal
      regeneration.

PMID- 8148313
TI  - Establishment and characterization of new IgD lambda type myeloma cell lines,
      MOLP-2 and MOLP-3, expressing CD28, CD33 antigens and the IL-6 receptor.
AB  - Multiple myeloma cell lines, MOLP-2 and MOLP-3, were established from the
      peripheral blood of a patient in leukemic phase of multiple myeloma. Both cell
      lines express the IL-6 receptor, CD28 T cell-associated antigen and CD33 myeloid
      associated antigen. IgD lambda immunoglobulin was found in the culture
      supernatants of both MOLP-2 and MOLP-3.

PMID- 8148314
TI  - [Human cell line of intracranial B cell lymphoma].

PMID- 8148315
TI  - [DNA fingerprint method of the cultured cells].
AB  - DNA fingerprint method is very available not only to examine the cross
      contamination of cultured cell lines and their origins and but to know the
      somatic mutation frequency in the cultured cells by exposure of radiation and
      chemicals. The method for DNA fingerprint was grouped in the following four types
      in term of probe; multilocus minisatellite probe, simple sequence repeat probe,
      locus specific minisatellite probe and repeat unit sequence variation in
      minisatellites.

PMID- 8148316
TI  - [Apoptosis: from its molecular structure to therapeutic application].

PMID- 8148317
TI  - Non-random employment of V beta 6 and J beta gene elements and conserved amino
      acid usage profiles in CDR3 regions of human fetal and adult TCR beta chain
      rearrangements.
AB  - We have studied the usage of V beta 6, D beta, and J beta elements, and the
      composition of the CDR3 regions of human fetal TCR beta chain rearrangements in a
      17 week old fetal thymus and in fetal liver, bone marrow, spleen, and cord blood
      at 11 and 13 weeks of gestation. These fetal sequences were compared with TCR
      beta chain rearrangements obtained from post-partum thymus, adult spleen, and
      adult peripheral blood mononuclear cells. Both fetal and adult TCR V beta 6
      rearrangements exhibited a non-random usage of V beta and J beta elements. Up to
      90% of the sequences obtained at 11 weeks of gestation used J beta 2 elements,
      most notably J beta 2.1. In the 13 and 17 week old fetal and in the adult
      tissues, J beta 1 elements were used in approximately 30% of the rearrangements
      while, within the J beta 2 rearrangements, J beta 2.1 and J beta 2.7 were used
      most frequently. Both fetal and adult TCR beta chain CDR3 regions showed non
      random usage of amino acids. However, the early fetal repertoire was further
      limited due to the relative absence of N-regions in up to 60% of the 11 and 13
      week old TCR beta chain rearrangements, resulting in smaller antigen binding
      sites. In fetal and adult TCR beta chain rearrangements the distribution patterns
      of the length of N-regions and the usage profiles of J beta elements were similar
      in hematopoietic and peripheral organs, suggesting no apparent preference for
      particular TCR beta chain rearrangements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148318
TI  - Class II histocompatibility molecules associate with calnexin during assembly in
      the endoplasmic reticulum.
AB  - Class II histocompatibility antigens are composed of polymorphic alpha and beta
      polypeptides which associate in the endoplasmic reticulum (ER) with a third, non
      polymorphic invariant polypeptide (Ii). The alpha beta Ii complexes are
      subsequently transported through the Golgi to the endosomes, where the Ii chain
      dissociates before the alpha beta complex is transported to the cell surface.
      Results from transport-defective class II expression variant studies suggest that
      class II intracellular transport is regulated in multiple intracellular
      compartments. Consistent with this, a large number of studies have demonstrated
      that protein folding and/or oligomerization is facilitated in the ER by a class
      of proteins collectively known as molecular chaperones. In this report, we show
      that the ER-resident protein calnexin associates with human and murine class II
      antigens. Specifically, calnexin associates in the ER with free Ii polypeptides
      and partially assembled wild-type class II complexes, including A alpha and/or A
      alpha Ii complexes, as well as with alpha beta dimers isolated from class II
      transport-defective cells. Calnexin also physically associates with alpha beta Ii
      complexes, but not with mature alpha beta dimers. These results suggest that
      calnexin may regulate class II intracellular transport by facilitating the
      production of transport competent molecules out of the ER. In addition, we report
      that the nucleotide sequence of the gene encoding murine calnexin shows a high
      degree of homology to human IP90 and dog calnexin at both the nucleotide and
      deduced amino acid sequence level. The isolation of cDNA fragments encoding
      murine calnexin will allow us to further evaluate the functional consequences of
      calnexin-class II interaction.

PMID- 8148319
TI  - Quantitation of human influenza virus-specific cytotoxic T lymphocytes:
      correlation of cytotoxicity and increased numbers of IFN-gamma producing CD8+ T
      cells.
AB  - To study virus-specific cytotoxic T lymphocyte (CTL) activity at the single cell
      level, an IFN-gamma specific ELISPOT assay was adapted to elucidate the frequency
      of influenza-specific CTLs together with a standard cytotoxic 51Cr-release assay.
      Peripheral blood mononuclear cells (PBMCs) from human volunteers were cultured
      with influenza virus-infected autologous cells; following 3 or 7 days of culture,
      T cell subsets were assessed for IFN-gamma production by IFN-gamma-specific
      ELISPOT and ELISA, while IFN-gamma mRNA expression was determined by reverse
      transcriptase-polymerase chain reaction (RT-PCR). Influenza virus-specific CTL
      activity was measured in a 4 h 51Cr-release assay. Culture of PBMC with
      autologous A/Taiwan influenza (H1N1)-infected stimulator cells resulted in IFN
      gamma spot forming cells (SFCs) at 3 days that increased after 7 days of
      incubation. Numbers of IFN-gamma SFCs directly correlated with levels of secreted
      IFN-gamma and higher levels were seen in supernatants from 7 day cultures. RT-PCR
      analysis (35 cycles of amplification) showed greater IFN-gamma mRNA in T cells
      isolated from 7 day cultures. Separate aliquots of T cells from these cultures
      were also assessed for virus-specific cytotoxicity and T cells from 7 day (but
      not from 3 day) cultures induced high 51Cr release. Analysis indicated a
      significant direct correlation between level of cytotoxicity, number of IFN-gamma
      SFCs, and amount of IFN-gamma in culture supernatants. Studies with purified T
      cell subsets showed that elevated IFN-gamma SFCs, IFN-gamma synthesis, and
      cytotoxic activity were associated with CD4-CD8+ T cells but not with the CD4+CD8
      T cell subset.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148320
TI  - Mechanism for transforming growth factor beta regulation of alpha mRNA in
      lipopolysaccharide-stimulated B cells.
AB  - Transforming growth factor (TGF)-beta has been shown to stimulate isotype
      switching to IgA in cultures of lipopolysaccharide (LPS)-stimulated B cells. The
      induction of isotype switching is associated with the appearance of novel
      germline alpha transcripts that cannot be found in cultures stimulated with LPS
      alone. TGF-beta also increases the steady state level of productive alpha mRNA.
      In order to further elucidate both the role of TGF-beta and germline transcripts
      in isotype switching to IgA in B cells, the mechanism responsible for the changes
      in alpha mRNA was investigated. The increase in alpha mRNA which does not occur
      until day 2 of culture continues until at least day 4. Nuclear run-on analysis
      demonstrated that TGF-beta does not significantly increase the rate of
      transcription of either germline or productive alpha mRNA after 12, 24, or 48 h
      of culture. However, by day 2 of culture TGF-beta increases the half-life of
      alpha mRNA. These findings support the idea that TGF-beta acts as a secondary
      signal to stimulate isotype switching to IgA in a population that has already
      received a signal that drives it toward IgA production. In addition these studies
      suggest that either the germline transcripts or processing of pre-germline alpha
      mRNA transcripts plays a role in targeting recombination.

PMID- 8148321
TI  - Physiological cell death in B lymphocytes: I. Differential susceptibility of WEHI
      231 sublines to anti-Ig induced physiological cell death and lack of correlation
      with bcl-2 expression.
AB  - WEHI-231 is a murine lymphoma generally considered to represent an immature B
      cell. Cross-linking of slg on WEHI-231 leads to growth arrest and eventually
      physiological cell death (PCD). We characterized three sublines of WEHI-231 by
      flow cytometry and compared their responses with slg cross-linking. All sublines
      had identical expression of a series of common B cell surface markers (IgM, IgD,
      Fc gamma R, ICAM-1, and CD45), but one was I-A-. Despite the phenotypic
      similarities between these sublines, anti-IgM caused aptotosis in only two
      sublines, although it inhibited growth in all three. The growth arrest induced by
      anti-IgM was reversible by lipopolysaccharide and Th2 clones and independent of
      Fc gamma R engagement. Anti-IgD, unlike anti-IgM, induced neither growth arrest
      nor apoptosis. To further compare the sublines' susceptibility to PCD, we
      investigated their responses to anti-IgM by ultrastructural morphology,
      [3H]thymidine release, propidium iodide exclusion, and incorporation into DNA. By
      all these experimental criteria, two of the WEHI-231 sublines were susceptible to
      PCD while the third demonstrated remarkable resistance to anti-IgM, but not
      irradiation or Th1-induced PCD. This differential susceptibility to PCD did not
      correlate with either bcl-2 levels in the resting cells or to the decrease in bcl
      2 expression following slg engagement. We discuss the implications of these
      findings for our understanding of PCD in B cells.

PMID- 8148322
TI  - Pre-B cells adhere to fibronectin via interactions of integrin alpha 5/alpha V
      with RGDS as well as of integrin alpha 4 with two distinct V region sequences at
      its different binding sites.
AB  - The present study aimed to develop an assay system capable of directly examining
      the adhesion of cells to each cell-binding site on fibronectin (FN) and to
      investigate molecular mechanisms underlying the pre-B cell-FN interaction.
      Treatment of culture plates with 3-(2-pyridyldithio) propionic acid N
      hydroxysuccinimide ester and subsequently with dithiothreitol (DTT) allowed the
      plates to adsorb DTT-treated extracellular matrix (ECM) proteins as well as
      synthetic peptides containing cysteine at the N-terminal. These treatments
      produced culture plates coated with ECM proteins or peptides corresponding to its
      cell-binding sequences, i.e. three sites on FN termed RGDS, LDVP, and RGDV. Pre-B
      cells exhibited potent adhesiveness to FN-coated plates. Its FN binding was most
      efficiently inhibited by adding a combination of free forms of RGDS, LDVP, and
      RGDV peptides, indicating the involvement of these three cell-binding sites in
      the pre-B cell-FN interaction. In accordance with this, pre-B cells exhibited
      considerable and potent binding to the respective RGDS-, LDVP-, or RGDV-coated
      plates. Such binding was specific for the peptide used for coating, because each
      binding to a given peptide-coated plate was inhibited only by addition of a
      homologous free peptide. This assay system further demonstrated that the pre-B
      cell binding to RGDS was mediated by the alpha 5 and alpha v integrins, whereas
      the binding to LDVP and RGDV was mediated by the alpha 4 integrin. It was also
      shown that LDVP binding was inhibited by LDVP but not by RGDV and, likewise, RGDV
      binding was inhibited by RGDV but not by LDVP.2+ interaction involving complex
      molecular mechanisms.

PMID- 8148323
TI  - Dynamic changes in mRNA expression of neutrophils during the course of acute
      inflammation in rabbits.
AB  - To examine RNA/protein synthesis of neutrophils and related dynamic changes
      during the inflammatory process, we investigated mRNA expressions in neutrophils,
      by RNA blot hybridization analyses using 12 different rabbit gene probes. We
      first selected five candidate genes encoding inflammation-related proteins, i.e.
      tumor necrosis factor (TNF-alpha) IL-1 alpha, IL-1 beta, neutrophil activating
      peptide-1/IL-8 (NAP-1/IL-8) and monocyte chemoattractant protein (MCP)-1. We
      further selected several genes on basis of the results from gene subtraction
      between cDNA libraries from neutrophils at an early (5 h) and at a late (24 h)
      stage of casein-induced acute peritonitis in rabbits, i.e. immune activation gene
      2 (Act-2), migration inhibitory factor-related protein-8 (MRP-8), MRP-14, gamma
      actin, and formyl-methionyl-leucyl-phenylalanine receptor (fMLP-R), and ferritin
      light (L) chain. In addition to these genes we used ferritin heavy (H) chain
      gene, another component of the ferritin molecule. We examined mRNA expressions by
      cytoplasmic slot blot analysis of the above 12 genes in neutrophils obtained from
      blood and from various stages of casein-induced inflammation in rabbits. The
      observed patterns of mRNA expression kinetics were classified into three. Pattern
      1: mRNAs of MRP-8, MRP-14, and gamma-actin were constitutively expressed in blood
      neutrophils, and increased rapidly after emigration into inflammatory sites.
      Pattern 2: mRNAs of IL-1 beta, NAP-1/IL-8, Act-2, and fMLP-R were undetectable in
      blood neutrophils, and were induced rapidly after the onset of inflammation.
      Pattern 3 mRNAs of ferritin L and H chain were induced slowly, and increased with
      progression of the inflammatory process.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148324
TI  - Influence of surrogate L chain on DHJH-reading frame 2 suppression in mouse
      precursor B cells.
AB  - DHJH rearrangements start in progenitor and precursor B cells and occur in three
      reading frames (rf). A strong bias for rf I has been noticed in murine and
      chicken antibodies, while the representation of rf II has been found suppressed
      both in peripheral as well as in precursor B cells. H chain gene loci DHJH
      rearranged in rf II are potentially capable of expressing a truncated DHJHC mu
      protein on the cell surface. Mice incapable of expressing this protein on the
      surface have previously been shown to have all reading frames represented in near
      equal frequency, suggesting that membrane-bound DHJHC mu protein is involved in
      the suppression of rf II. In this paper we show that suppression of rf II is not
      yet established in c-kit+ CD43+ IL-7/stromal cell-reactive pre-B I cells of fetal
      liver at day 15 of gestation, but becomes established when such precursor cell
      populations are expanded in vitro on stromal cells in the presence of IL-7. H
      chain gene loci using the DQ52 segment for rearrangements (which contains a stop
      codon in rf II, thus being unable to make DHJHC mu protein) do not show rf II
      suppression under these conditions. The same type of fetal liver-derived pre B-I
      cells from lambda 5 deficient mice also do not show rf II suppression after in
      vitro expansion. Bone marrow-derived pre B-I cells from normal mice assayed ex
      vivo and expanded in vivo show rf II suppression, while the corresponding pre-B I
      cells from lambda 5T mice do not. Collectively these experiments suggest that
      surrogate L chain is involved in rf II suppression. This may happen by inhibition
      of proliferation of pre-B cells expressing a complex of DHJHC mu protein and
      surrogate L chain.

PMID- 8148325
TI  - Flow cytometric analysis reveals unexpected shared antigens between
      histologically defined populations of thymic stromal cells.
AB  - Utilizing flow cytometry, the expression of antigens recognized by six thymic
      stromal cell (TSC) reactive mAbs was investigated on fresh TSCs and TSC lines. It
      was found that some thymic epithelial cells and dendritic cells share antigenic
      phenotypes, and that most TSC reactive mAbs have a more extensive distribution
      than would have been predicted from immunohistology. While these findings
      illustrate the higher sensitivity of flow cytometric analysis, they more
      importantly emphasize the great complexity of TSC that direct T cell development.
      In order to identify the molecular parameters that define the various steps
      involved in T cell differentiation, TSC antigens (non-TCR/MHC/co-receptor) that
      are functional will have to be identified. This study represents the initial
      steps in characterizing such antigens.

PMID- 8148326
TI  - Transcriptional regulation of immunoglobulin gene expression by anti-Ig.
AB  - When transfected into mouse splenic B cells stimulated with lipopolysaccharide
      (LPS) the expression of DNA vectors containing the chloramphenicol acetyl
      transferase gene under the control of a SP6 kappa promoter and the Ig heavy chain
      intron enhancer could be down-regulated 5- to 10-fold by treatment of the cells
      with anti-Ig prior to transfection. Exchanging the SP6 kappa promoter by minimal
      promoters consisting of an octamer or a SP1 motif linked to TATA box did not
      impair the anti-Ig induced down-regulation while inserting a rabbit beta-globin
      promoter did. The transcriptional regulation could be observed after replacing
      the Ig heavy chain intron enhancer with a SV40 enhancer, or duplicated minimal Ig
      heavy chain enhancers containing or lacking the octamer element. The down
      regulation was not dependent on the level of transcriptional stimulation
      observed. A difference in Oct2 expression could neither be detected at the RNA
      nor protein level after treatment of LPS stimulated B cells with anti-Ig or
      phorbol-dibutyrate. Anti-Ig treatment, but not phorbol-di-butyrate treatment,
      induced increased levels of AP1 and NF kappa B transcription factors. Thus,
      either differentiation specific transcriptional control of Ig genes is exerted
      via transcription factors common to several distinct enhancers or via
      transcriptional adaptor molecules that can interact with several distinct DNA
      binding proteins.

PMID- 8148327
TI  - Non-coordinate synthesis of MHC class II proteins and invariant chains by
      epidermal Langerhans cells derived from short-term in vitro culture.
AB  - Epidermal cells (EC) prepared from Lewis rat skin contained 2-3% class II+, LCA+
      Langerhans cells (LC). LC enriched from freshly isolated EC suspensions proved
      highly effective accessory cells when presenting the nominal antigen OVA to an
      RT1.Bl-restricted ovalbumin (OVA)-specific rat T cell clone. Short-term
      preculture of the EC resulted in diminished OVA presenting capacity of the LC.
      Flow cytometry (FCM) analysis of class II and gamma chain expression revealed an
      up-regulation of class II on the LC's cell surface, consistent with earlier
      findings in mouse and human. However, while the presence of gamma chains in mouse
      LC was reported to decline to negligible levels during culture we observed
      substantial gamma surface expression on 3 day cultured rat LC, accompanied by
      increasing quantities of gamma inside the cells as revealed by FCM analysis on
      permeabilized cells. Biosynthetic labeling of panning-enriched LC from fresh and
      cultured EC confirmed and extended the immunocytological analysis. In contrast to
      the synthesis of class II proteins, that declined during culture to background
      levels, gamma chain synthesis was strongly augmented after 1 day in culture and
      remained at prominent levels throughout the culture period. In LC pulse labeled
      for 4 h and subjected to a 3 day chase period prominent quantities of labeled
      class II complexes were detectable with the majority of the dimers exhibiting the
      compact (C)-type folding form. On the basis of our findings a novel function of
      the invariant gamma chain is suggested to be effective in LC.

PMID- 8148328
TI  - Retroviruses--a clue to autoimmunity?

PMID- 8148329
TI  - Changing concepts in ptosis surgery.

PMID- 8148330
TI  - Human T lymphotropic virus type 1 uveitis after Graves' disease.
AB  - A distinct clinical entity of uveitis associated with human T lymphotropic virus
      type 1 (HTLV-I) has been reported previously. During the period between January
      1989 and April 1992, 93 patients were observed with HTLV-I uveitis and a
      significant correlation was found between Graves' disease and HTLV-I uveitis.
      Sixteen of the 93 patients with HTLV-I uveitis (17.2%) had a previous history of
      Graves' disease. Fifteen patients were female (15/60, 25.0%) and one was male
      (1/33, 3.0%). Interestingly, uveitis occurred after the onset of Graves' disease
      in all cases. On the other hand, none of 222 patients with idiopathic uveitis who
      were seronegative to HTLV-I had a history of Graves' disease. Although the
      mechanisms by which HTLV-I causes the correlation between uveitis and Graves'
      disease are unknown, the present data suggest that immune mediated or autoimmune
      mechanisms are involved in HTLV-I uveitis.

PMID- 8148331
TI  - Adjustable sutures in eyelid surgery for ptosis and lid retraction.
AB  - New techniques are described and illustrated for ptosis and lid retraction
      surgery in which the sutures holding the upper eyelid position are adjustable
      postoperatively. In the anterior approach, the sutures pass from the levator
      muscle through the anterior surface of the tarsal plate at the position of the
      skin crease and are tied at the skin crease incision. In the posterior approach,
      the sutures pass from the levator muscle through the cut upper edge of the tarsal
      plate and are tied at the position of the desired skin crease. The techniques
      allow the lid height to be adjusted for over and undercorrection medially,
      centrally, laterally, or overall if required, thereby achieving the optimal
      surgical result without altering the position of the skin crease. Suture
      adjustment is a simple procedure and is recommended at 24 hours.

PMID- 8148332
TI  - A comparison of automated static dark stimuli with the Humphrey STATPAC program
      in glaucomatous visual field loss.
AB  - Visual field examination is conventionally performed with bright stimuli on a
      dark background. Dark stimuli on a bright background, however, may provide
      different information as light increases and decreases are subject to parallel
      processing in the visual pathway. Twenty five eyes with primary open angle
      glaucoma and visual field loss were examined with the Humphrey visual field
      analyser thresholding program 30-2 and the computer assisted moving eye
      campimeter (CAMEC) using static dark stimuli at four different Weber contrast
      levels of -10 (n = 9), -22 (n = 25), -37 (n = 14), and -76% (n = 25) on a cathode
      ray tube with a background luminance of 10 cd/m2. The cumulative results obtained
      with STATPAC 'pattern deviation' empirical probability maps and the results from
      each contrast of the dark stimulus at identical test locations were compared at
      eccentricity annuli bands of 4-9, 10-20, and 21-28 degrees. Dark stimuli of lower
      contrast provided higher abnormal point detection rates. Furthermore, visual
      field defects to the low contrast dark stimuli were more extensive than those to
      the luminous stimuli. In conclusion, dark stimuli allowed the delineation between
      glaucomatous field defects and the normal regions in the central visual field.

PMID- 8148333
TI  - Representation of the visual field in the occipital striate cortex.
AB  - The representation of the field of vision in the human striate cortex is based on
      the Holmes map in which about 25% of the surface area of the striate cortex is
      allocated to the central 15 degrees of vision. Following the introduction of
      computed tomography of the brain, the accuracy of the Holmes map was apparently
      confirmed by clinical/radiological correlation, but a revision has been proposed
      by Horton and Hoyt based on a magnetic resonance imaging study of three patients
      with visual field defects due to striate lesions. They propose that the central
      cortical representation of vision occupies a much larger area. This study reviews
      the perimetric and imaging findings in a larger series of patients with striate
      cortical disease and provides support for the revised representation. The
      clinical phenomenon of macular sparing and its relation to representation of the
      macula at the occipital pole is also discussed.

PMID- 8148334
TI  - Electroretinogram b/a wave ratio improvement in central retinal vein obstruction.
AB  - The electroretinogram (ERG), especially the b/a wave ratio, is considered a good
      indicator of retinal ischaemia in central retinal vein obstruction (CRVO). Seven
      CRVO patients who showed b/a wave ratio improvement from < 1.0 [negative type (-)
      ERG] to > or = 1.0 and one from 1.07 to 1.53 were studied. Three mechanisms of
      change were observed: firstly, the b-wave amplitude increased without an a-wave
      amplitude decrease (group A, n = 2); secondly, the b-wave amplitude increased
      with an a-wave amplitude decrease (group B, n = 4); and, thirdly, both decreased,
      but the a-wave amplitude decreased more markedly (group C, n = 2). In group A,
      the visual acuities improved markedly. In group B, the visual acuities improved
      in two cases in which the b-wave amplitude reached the normal range; the visual
      acuities did not improve in two cases in which the b-wave amplitude did not reach
      the normal range. In group C, the visual acuities remained poor. The negative (-)
      ERG or significantly reduced b/a wave ratio is associated with ischaemic CRVO and
      did not occur because of the filtering effect of the haemorrhage, which may
      reduce the stimulus light for the ERG. Improvement of the reduced b/a wave ratio
      with an increased b-wave amplitude was accompanied by improvements in fundus
      appearance and visual acuity in CRVO. The results suggest that the retinal
      ischaemia in CRVO, as revealed by the ERG and fluorescein angiogram, may be
      reversible in some cases.

PMID- 8148335
TI  - 193 nm excimer laser sclerostomy in pseudophakic patients with advanced open
      angle glaucoma.
AB  - A modified open mask system incorporating an en face air jet to dry the target
      area during ablation and a conjunctival plication mechanism, which allows ab
      externo delivery of the 193 nm excimer laser without prior conjunctival
      dissection, has been developed to form small bore sclerostomies accurately and
      atraumatically. Full thickness sclerostomies, and sclerostomies guarded by a
      smaller internal ostium can be created. A pilot therapeutic trial was conducted
      in pseudophakic patients with advanced open angle glaucoma. Six full thickness
      sclerostomies (200 microns and 400 microns diameter) and three guarded
      sclerostomies were created in nine patients by 193 nm excimer laser ablation
      (fluence per pulse 400 mJ/cm2, pulse rate 16 Hz, air jet pressure intraocular
      pressure +25 mm Hg). After 6 months' follow up, intraocular pressure was
      controlled (< or = 16 mm Hg) in eight of the nine patients (6/9 without
      medication). Early postoperative complications included hyphaema (trace--2.5 mm)
      (6/9), temporary fibrinous sclerostomy occlusion (4/9), profound early hypotony
      (all patients without fibrinous occlusion), and suprachoroidal haemorrhage in one
      case. Conjunctival laser wounds were self sealing. Small bore laser sclerostomy
      procedures are functionally equivalent to conventional full thickness procedures,
      producing early postoperative hypotony, with an increased risk of suprachoroidal
      haemorrhage in association with this. Further research is required to improve
      control over internal guarding in excimer laser sclerostomy before clinical
      trials of this technique can safely proceed.

PMID- 8148336
TI  - The treatment and follow up of adult chlamydial ophthalmia.
AB  - Sixty two patients diagnosed as having adult chlamydial ophthalmia were treated
      with oral doxycycline and roxithromycin in association and tetracycline eye wash
      for 2 weeks. Chlamydial ophthalmia was diagnosed by laboratory detection of the
      micro-organism in ocular specimens using direct immunofluorescent monoclonal
      antibody staining for Chlamydia trachomatis, chlamydial culture in cycloheximide
      treated McCoy cells, and Giemsa staining. An immunoenzymatic method for detection
      of specific IgG and IgA in patients' serum was used as an additional test to
      confirm the diagnosis. All patients were reexamined 3 weeks after completing
      their course of antibiotics and in the case of persistent infection a further
      course of treatment was given. With this treatment regimen 48 out of 62 patients
      (77.4%) were cured after three courses. Because of the risks of an inadequate
      response to therapy, we recommend a proper post-treatment follow up in all
      patients with chlamydial eye infections.

PMID- 8148337
TI  - Percutaneous anaesthesia with a lignocaine-prilocaine cream (Emla) for eyelid
      skin surgery.
AB  - Epicutaneous application of the anaesthetic cream Emla (lignocaine and
      prilocaine), to induce percutaneous anaesthesia in 38 patients scheduled for
      eyelid skin surgery is presented. The cream was applied 60 to 90 minutes before
      operation. In 36 out of the 38 patients (94.8%) no supplementary analgesia was
      required. The pain during the procedure was rated either as no pain in 29
      patients (76.3%), slight pain in five patients (13%), moderate pain in two
      patients (5.2%), and severe pain in two patients (5.2%). Percutaneous anaesthesia
      induced by Emla cream is a useful and painless alternative method for analgesia
      in eyelid skin surgery.

PMID- 8148338
TI  - Distribution and characterisation of rat choroidal mast cells.
AB  - Despite the implication that choroidal mast cells are involved in the onset of
      experimental autoimmune uveoretinitis (EAU), a widely used animal model of
      uveoretinitis, little is known of these cells. In the present study the
      distribution, total number, regional density, and phenotype of choroidal mast
      cells were examined in Lewis, Wistar Furth, PVG/c, and brown Norway rats.
      Choroidal mast cells were predominantly associated with arteries and arterioles
      of more than 30 microns diameter which lie in the outer (sclerad) choroid. The
      density of mast cells was greatest in the posterior choroid with density
      diminishing anteriorly. The choroid of male Lewis rats contained significantly
      greater number of mast cells than that of females (p < 0.01). Histochemical
      (Alcian blue/safranin) and immunohistochemical (anti-rat mast cell protease I and
      II monoclonal antibodies) studies revealed choroidal mast cells were of the
      connective tissue type. However, granule proteinase content appeared less than
      that of well characterised connective tissue mast cell populations such as those
      in mesentery and skin. Lewis rats exhibited the highest density of choroidal mast
      cells (23.6 (SD 1.2)/mm2), Wistar Furth approximately half that of Lewis (13.5
      (0.7)/mm2) while PVG/c and brown Norway rats had very low densities (3.06(0.3);
      1.95(0.2/mm2 respectively). These studies provide valuable choroidal mast cell
      data for rats which may have implications for our understanding of experimental
      models of intraocular inflammation and clinical uveitis.

PMID- 8148339
TI  - The history of artificial eyes.

PMID- 8148340
TI  - Infectious endophthalmitis after cataract surgery.

PMID- 8148341
TI  - Periorbital necrotising fasciitis.

PMID- 8148342
TI  - Ocular complications associated with bungee jumping.

PMID- 8148343
TI  - Bungee jumping and intraocular haemorrhage.

PMID- 8148344
TI  - Development of neovascular glaucoma in the course of interferon alfa therapy for
      hepatitis type C.

PMID- 8148345
TI  - Sub-Tenon's infiltration of local anaesthetic with hyaluronidase.

PMID- 8148346
TI  - Indocyanine green enhanced diode laser photocoagulation of subretinal neovascular
      membranes.

PMID- 8148347
TI  - Ophthalmic complications after bungee jumping.

PMID- 8148348
TI  - ApoB metabolism in familial hypercholesterolemia. Inconsistencies with the LDL
      receptor paradigm.
AB  - The biology of the low-density lipoprotein (LDL) receptor has been examined in
      detail, and a paradigm for LDL metabolism has evolved from comparative studies of
      cholesterol metabolism in a variety of cells cultured from normal individuals and
      subjects with familial hypercholesterolemia (FH). Cultured cells from patients
      with homozygous FH lack a functional LDL receptor and show diminished LDL
      clearance, induction of the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA)
      reductase, increased cholesterol synthesis, decreased cholesterol ester
      production, and depleted cholesterol ester stores. The observed decrease in the
      fractional catabolic rate (FCR) of LDL is attributed to the mutated LDL receptor
      gene. However, in the experimental animal model of this disease, the Watanabe
      heritable hyperlipidemic (WHHL) rabbit, cholesterol ester stores are increased,
      while hepatic cholesterol synthesis is decreased. Furthermore, in humans HMG-CoA
      reductase is suppressed, and the LDL apolipoprotein (apo) B production rate is
      increased in patients with FH. These findings raise questions about the adequacy
      of the paradigm in understanding hepatic cholesterol metabolism in vivo. In
      humans, apoB metabolism is believed to be principally determined by the liver,
      where apoB is both synthesized and catabolized. Assuming the neutral lipid
      content of the liver is the major determinant of apoB metabolism, we postulated
      that the changes in apoB metabolism in FH are predictable when based on the
      assumption of an increase in hepatic cholesterol and cholesterol ester content,
      as observed both in the WHHL rabbit and in humans. We examined this hypothesis in
      vivo in patients with heterozygous FH by using tracer kinetic methodology and
      have used similar data from normal and hypertriglyceridemic (HTG) subjects as
      controls. Whereas normal and HTG subjects secrete apoB primarily as large,
      triglyceride-enriched very-low-density lipoprotein (VLDL), heterozygous FH
      patients have an absolute decrease in apoB production and secrete almost 40% of
      apoB as smaller intermediate-density lipoprotein (IDL)/LDL. In normal humans,
      about half of secreted apoB is catabolized rather than being converted to LDL. In
      HTG subjects two thirds of apoB follows this same route, by which VLDL remnants
      remaining after triglyceride hydrolysis are largely returned to the liver. In
      contrast, in FH subjects secreted apoB is fully converted to LDL. Thus, although
      total apoB secretion is reduced in FH subjects, total LDL production is greater
      than in either normal or HTG subjects. Under basal conditions the elevated LDL in
      heterozygous FH is due to both decreased LDL receptor-mediated catabolism and
      increased LDL production. However, the number of LDL receptors actually expressed
      is suppressed below the number of potentially functional receptors.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8148349
TI  - Concentrations of apolipoprotein A-I-containing particles in patients with
      hypoalphalipoproteinemia.
AB  - This study was performed to determine relations among concentrations of high
      density lipoprotein (HDL) apolipoprotein (apo) A-I and apoA-II and lipoproteins
      with apoA-I only (LpA-I) and with both apoA-I and apoA-II (LpA-I:A-II) in
      patients with low plasma levels of HDL cholesterol. Seventy-seven middle-aged men
      with low HDL cholesterol levels (< 40 mg/dL) were compared with 37 middle-aged
      men with normal HDL cholesterol levels (> 40 mg/dL). Low-HDL patients were
      divided into those with normotriglyceridemia (triglycerides < 250 mg/dL; n = 49)
      and hypertriglyceridemia (triglycerides > or = 250 mg/dL; n = 28). Total apoA-I
      and apoA-II concentrations and apoA-I levels in LpA-I were significantly lower in
      the two low-HDL groups compared with control subjects. Although low-HDL patients'
      apoA-I levels were numerically lower in LpA-I:A-II compared with control
      subjects' levels, the differences were not statistically significant. Thus, there
      is a preferential reduction in apoA-I levels of LpA-I compared with LpA-I:A-II in
      patients with low HDL cholesterol. This preferential reduction in LpA-I levels
      was observed in both normotriglyceridemic and hypertriglyceridemic patients.
      However, among low-HDL patients levels of apoA-I in LpA-I did not distinguish
      between those with and without coronary heart disease.

PMID- 8148350
TI  - Hyperinsulinemia predicts multiple atherogenic changes in lipoproteins in elderly
      subjects.
AB  - Several studies have shown that hyperinsulinemia and insulin resistance are
      associated with high triglyceride and low high-density lipoprotein (HDL)
      cholesterol levels. However, previous studies have been cross-sectional, and thus
      the presence of hyperinsulinemia or insulin resistance could be a consequence of
      the underlying lipid disorder instead of its cause. Therefore, we examined the
      relation of fasting insulin level measured in a cross-sectional study in
      nondiabetic subjects 65 to 74 years old (n = 881) to the risk of developing lipid
      disorders 3.5 years later. The incidence of the following lipid abnormalities was
      calculated: hypertriglyceridemia (n = 49/732, incident cases/subjects free of the
      particular disorder at baseline), high low-density lipoprotein (LDL) cholesterol
      level (n = 43/696), low HDL cholesterol level (n = 33/708), high apolipoprotein
      (apo) B level (n = 72/699), low apoAI level (n = 47/711), low serum LDL
      cholesterol/serum apoB ratio (n = 55/685), and low serum HDL cholesterol/serum
      apoAI ratio (n = 48/707). Baseline insulin level was not significantly associated
      with the development of high LDL cholesterol or low HDL cholesterol levels.
      Baseline insulin was associated with the development of hypertriglyceridemia
      (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12 to 2.40; P = .011),
      high apoB (OR, 1.54; 95% CI, 1.13 to 2.10; P = .006), low apoAI (OR, 1.72; 95%
      CI, 1.22 to 2.42; P = .002), low LDL cholesterol/apoB ratio (OR, 1.99; 95% CI,
      1.36 to 2.90; P < .001), and low HDL cholesterol/apoAI ratio (OR, 1.93; 95% CI,
      1.34 to 2.79; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148351
TI  - The human apolipoprotein(a)/plasminogen gene cluster contains a novel homologue
      transcribed in liver.
AB  - Lipoprotein(a) is an atherogenic lipoprotein whose function and plasma
      concentration reflect the structure and regulation of the apolipoprotein(a) gene.
      Apolipoprotein(a) is a close homologue of plasminogen, and their genes are
      tightly linked on chromosome 6. To further characterize these genes, we analyzed
      overlapping human genomic yeast artificial chromosome clones, which revealed a
      cluster of four highly homologous genes encoding apolipoprotein(a), plasminogen,
      and two apolipoprotein(a)-related genes (rg) or pseudogenes. Hybridization
      analysis and reverse transcriptase polymerase chain reaction showed that one of
      these novel genes, designated apolipoprotein(a)rg-C, has a domain structure
      similar to apolipoprotein(a) and is transcribed in human liver. Three additional
      homologues designated as plasminogen-related genes are shown to be unlinked to
      this gene cluster and reside on chromosomes 2 and 4.

PMID- 8148352
TI  - Effect of dietary fat selection on plasma cholesterol synthesis in older,
      moderately hypercholesterolemic humans.
AB  - To study factors controlling plasma cholesterol levels, the effect of dietary fat
      type on cholesterol synthesis was examined in 15 hypercholesterolemic subjects
      (low-density lipoprotein [LDL] cholesterol > 130 mg.dL-1) consuming over a period
      of 32 days (1) a baseline diet (36% kcal as fat: 15% saturated, 15%
      monounsaturated, and 6% polyunsaturated fat; 180 mg cholesterol.1000 kcal-1) and
      diets meeting National Cholesterol Education Program step 2 criteria (30% kcal as
      fat, < or = 7% saturated fat, 80 to 85 mg cholesterol/Mcal), where two thirds of
      the fat was either (2) olive, (3) corn, or (4) canola oil. Plasma total, LDL, and
      high-density lipoprotein (HDL) cholesterol and triglyceride levels were
      determined at the end of each period. Cholesterol fractional synthesis rate (FSR)
      was also measured as the deuterium (D) incorporation into plasma total
      cholesterol relative to body D2O level (1.2 g D2O.kg-1 estimated body water) over
      24 hours. Absolute synthesis rates (ASRs) were determined as the product of FSR
      and rapid turnover cholesterol pool size. Plasma total and LDL cholesterol levels
      declined significantly (P < .005) on all plant-oil diets compared with the
      baseline diet; however, triglyceride levels were not different. FSRs were higher
      (P < .05) for the corn oil (0.0665 +/- 0.0097 pool.d-1) compared with baseline
      (0.0412 +/- 0.0060 pool.d-1) and olive oil (0.0409 +/- 0.0052 pool.d-1) but not
      canola oil (0.0492 +/- 0.0072 pool.d-1) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148353
TI  - Rice bran oil consumption and plasma lipid levels in moderately
      hypercholesterolemic humans.
AB  - The effect of rice bran oil, and oil not commonly consumed in the United States,
      on plasma lipid and apolipoprotein concentrations was studied within the context
      of a National Cholesterol Education Panel (NCEP) Step 2 diet and compared with
      the effects of canola, corn, and olive oils. The study subjects were 15 middle
      aged and elderly subjects (8 postmenopausal women and 7 men; age range, 44 to 78
      years) with elevated low-density lipoprotein (LDL) cholesterol (C) concentrations
      (range, 133 to 219 mg/dL). Diets enriched in each of the test oils were consumed
      by each subject for 32-day periods in a double-blind fashion and were ordered in
      a Latin square design. All food and drink were provided by the metabolic research
      unit. Diet components were identical (17% of calories as protein, 53% as
      carbohydrate, 30% as fat [< 7% as saturated fat], and 80 mg cholesterol/1000
      kcal) except that two thirds of the fat in each diet was contributed by rice
      bran, canola, corn, or olive oil. Mean +/- SD plasma total cholesterol
      concentrations were 192 +/- 19, 194 +/- 20, 194 +/- 19, and 205 +/- 19 mg/dL, and
      LDL-C concentrations were 109 +/- 30, 109 +/- 26, 108 +/- 31, and 112 +/- 29
      mg/dL after consumption of the rice bran, canola, corn, and olive oil-enriched
      diets, respectively. Plasma cholesterol and LDL-C concentrations were similar and
      statistically indistinguishable when the subjects consumed the rice bran, canola,
      and corn oil-enriched diets and lower than when they consumed the olive oil
      enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148354
TI  - Effects of linoleate-enriched and oleate-enriched diets in combination with alpha
      tocopherol on the susceptibility of LDL and LDL subfractions to oxidative
      modification in humans.
AB  - This report describes the effects of feeding linoleate- or oleate-enriched diets
      to subjects who were concurrently taking 1200 mg/d of alpha-tocopherol on the
      susceptibility of low-density lipoprotein (LDL) and buoyant and dense LDL
      subfractions to oxidation. LDL isolated from subjects who consumed linoleate
      enriched diets was more susceptible to copper-mediated oxidation, as measured by
      formation of conjugated dienes and lipid peroxides and loss of unsaturated fatty
      acids, compared with LDL isolated from subjects who consumed their usual or
      oleate-enriched diets. In all subjects, buoyant LDL had a higher content of alpha
      tocopherol per particle and a lower 18:2 to 18:1 ratio and was considerably more
      resistant to oxidation than dense LDL. Although dense LDL from all groups had
      comparable alpha-tocopherol levels, dense LDL from the linoleate group was most
      susceptible to oxidation, followed by that from the standard diet, whereas dense
      LDL isolated from the oleate diet group was most resistant. In summary, high
      dosages of alpha-tocopherol did not prevent enhanced susceptibility to oxidation
      of LDL isolated from subjects fed linoleate-enriched diets. Furthermore, dense
      LDL was more susceptible to oxidation than was buoyant LDL, and this effect was
      greatly exaggerated in the dense LDL isolated from subjects fed linoleate
      enriched diets. Conversely, dense LDL isolated from subjects fed oleate-enriched
      diets was the most protected. If oxidation of LDL is important in the
      pathogenesis of atherosclerosis, then these data suggest that in people with
      increased amounts of small, dense LDL, dietary enrichment in oleic acid may
      decrease the susceptibility of their LDL to oxidation.

PMID- 8148355
TI  - Impact of myristic acid versus palmitic acid on serum lipid and lipoprotein
      levels in healthy women and men.
AB  - The cholesterol-raising effect of dietary saturated fatty acids is largely
      accounted for by lauric, myristic, and palmitic acids. Dairy fat is a major
      source of myristic acid, and palm oil is especially rich in palmitic acid.
      Myristic acid is suspected of being much more cholesterolemic than palmitic acid,
      but direct comparisons have been lacking. We therefore fed 36 women and 23 men
      three diets that differed from each other in palmitic, oleic, and myristic acid
      content by about 10% of total energy. We used palm oil, high-oleic acid sunflower
      oil, and a specially produced high-myristic acid fat to achieve these
      differences. Each diet was consumed for 3 weeks in random order. Mean serum
      cholesterol was 4.53 mmol/L on the high-oleic acid diet, 4.96 mmol/L on the
      palmitic acid diet, and 5.19 mmol/L on the myristic acid diet (P < .0001 for all
      comparisons). Myristic acid raised low-density lipoprotein (LDL) cholesterol by
      0.11 mmol/L, high-density lipoprotein (HDL) cholesterol by 0.12 mmol/L, and
      apolipoprotein (apo) A-I by 7.2 mg/dL relative to palmitic acid; increases
      relative to oleic acid were 0.50 mmol/L for LDL cholesterol, 0.15 mmol/L for HDL
      cholesterol, 6.0 mg/dL for apoB, and 8.9 mg/dL for apoA-I (P < .01 for all
      comparisons). The HDL cholesterol and apoA-I levels on the palmitic and oleic
      acid diets were the same. None of the responses differed significantly between
      woman and men. Myristic acid and palmitic acid both caused high LDL cholesterol
      and apoB levels and low HDL to LDL ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148356
TI  - A dose-response study of the effects of dietary cholesterol on fasting and
      postprandial lipid and lipoprotein metabolism in healthy young men.
AB  - Despite many previous studies, controversy remains concerning the effects of
      dietary cholesterol on plasma cholesterol concentrations. In addition, the focus
      of previous studies has been fasting lipid and lipoprotein concentrations; there
      are no published studies with postprandial measurements. We studied the effects
      of four levels of dietary cholesterol intake on fasting lipid, lipoprotein, and
      apoprotein levels, as well as postprandial lipid levels, in a group of young,
      healthy men who were otherwise eating a low-fat, American Heart Association step
      1 diet. Twenty young, healthy men completed a randomized, four-way crossover
      design study to test the effects of an American Heart Association step 1 diet
      containing 0, 1, 2, or 4 eggs per day. Dietary cholesterol ranged from 128 to 858
      mg cholesterol per day. Each diet was eaten for 8 weeks, with a break between
      diets. Three fasting blood samples were obtained at the end of each diet period.
      In addition, blood samples were obtained just before and 2, 4, and 6 hours after
      ingestion of a standard lunch containing the various amounts of egg cholesterol.
      We also obtained blood 4 and 8 hours after the subjects ingested a standard, high
      fat formula. Fasting plasma total cholesterol concentrations increased by 1.47
      mg/dL (0.038 mmol/L) for every 100 mg dietary cholesterol added to the diet (P <
      .001). Low-density lipoprotein (LDL) cholesterol increased in parallel.
      Responsiveness varied but appeared to be normally distributed. Fasting plasma
      apoprotein B concentrations increased approximately 10% between the 0- and 4-egg
      diets and were correlated with changes in total and LDL cholesterol
      concentrations. Although there was a trend toward a greater response in men with
      an apoprotein E4 allele, this was not statistically significant. Fasting plasma
      cholesteryl ester transfer protein levels were higher only on the 4-egg diet, and
      changes in cholesteryl ester transfer protein levels between the 0- and 4-egg
      diets correlated with changes in total and LDL cholesterol. There were no
      differences in the postlunch or post-fat-formula responses of plasma lipids
      across the diets. Incubation of the 4-hour postlunch serum with J774 macrophages
      did not affect cell cholesteryl ester content at any level of dietary
      cholesterol. Cellular free cholesterol levels were slightly higher on each of the
      egg-containing diets versus the 0-egg diet. In summary, increases in dietary
      cholesterol resulted in linear increases in fasting total and LDL cholesterol in
      young, healthy men.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8148357
TI  - Dietary polyunsaturated fat decreases coronary artery atherosclerosis in a
      pediatric-aged population of African green monkeys.
AB  - The hypothesis tested was that juvenile African green monkeys consuming diets
      enriched with n-6 polyunsaturated fat from birth until young adulthood would have
      significantly less coronary artery atherosclerosis than comparable animals
      consuming diets enriched with saturated fat. African green monkeys (Cercopithecus
      aethiops, n = 108) of both sexes were fed atherogenic diets (0.8 mg
      cholesterol/kcal) throughout their lives so that death at 16, 32, or 60 months of
      age permitted quantification of atherosclerosis. In the coronary arteries, the
      average intimal area increased significantly with age (P = .02), showing
      increases of 28-fold and sevenfold between 32 and 60 months in the saturated fat-
      and polyunsaturated fat-fed groups, respectively. Young adult male animals at 60
      months of age were found to have significantly (P = .03) more coronary artery
      atherosclerosis than female animals. Animals fed polyunsaturated fat had
      significantly (P < or = .01) less coronary artery atherosclerosis. By 60 months
      of age in the animals consuming polyunsaturated fat, the average coronary artery
      intimal area was one fourth and the average size of the largest coronary intimal
      lesion was one fifth that in monkeys fed saturated fat. Low-density lipoprotein
      (LDL) cholesterol and LDL particle size were each found to be positively
      correlated with coronary artery atherosclerosis end points in both diet groups.
      In addition to the coronary arteries, atherosclerosis in the abdominal and
      thoracic aorta and carotid arteries was also evaluated; the coronary arteries
      were the only arterial system with significantly less atherosclerosis in the
      polyunsaturated fat group as measured by intimal area. However, evaluation of
      histological sections of abdominal aorta showed relatively more sterol clefts in
      the saturated fat-fed group, and more free cholesterol was measured, suggesting
      that lesions were more complicated in this group. These results show that dietary
      intervention early in life with n-6 polyunsaturated fat can be effective in
      decreasing the development of atherosclerosis, particularly in the coronary
      arteries of primates. This outcome supports the concept that dietary intervention
      beginning early in childhood can have beneficial effects on the coronary heart
      disease of later life.

PMID- 8148358
TI  - ACAT inhibition decreases LDL cholesterol in rabbits fed a cholesterol-free diet.
      Marked changes in LDL cholesterol without changes in LDL receptor mRNA abundance.
AB  - Rabbits fed low-fat, cholesterol-free diets containing casein as the sole protein
      source develop endogenous hypercholesterolemia (EH). To test the hypothesis that
      lipoprotein cholesteryl esters in EH rabbits are acyl coenzyme A:cholesterol
      acyltransferase (ACAT) derived, we treated EH rabbits with CI-976, a potent and
      selective ACAT inhibitor. In addition, since cholesterol and bile acid synthesis
      as well as low-density lipoprotein (LDL) receptor activity are reduced in EH
      rabbits, we determined whether changes in gene expression for 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase, 7 alpha-hydroxylase, and the LDL
      receptor might be associated with the efficacy due to ACAT inhibition. Compared
      with EH controls, CI-976-treated rabbits (50 mg/kg per day for 5 weeks) had
      decreased plasma total cholesterol (-43%), very-low-density lipoprotein (VLDL)
      cholesterol (-62%), LDL cholesterol (-43%), plasma apolipoprotein B (-23%), liver
      cholesteryl esters (-39%), LDL size, VLDL and LDL cholesteryl ester content
      (percent of total lipids), cholesteryl oleate/cholesteryl linoleate ratios in
      VLDL and LDL (25% to 30%), and ex vivo liver ACAT activity. The
      triglyceride/cholesteryl ester ratio increased twofold to fourfold in these
      apolipoprotein B-containing lipoproteins. Endogenous cholesterol absorption
      appeared to be unaffected by drug treatment. CI-976 failed to alter specific
      hepatic mRNAs involved in cholesterol metabolism, but comparisons among dietary
      control groups revealed a marked reduction in 7 alpha-hydroxylase mRNA, no change
      in LDL receptor mRNA, and an increase in HMG-CoA reductase mRNA in EH rabbits
      compared with normal chow-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148359
TI  - Modulation of thrombotic responses in moderately stenosed arteries by cigarette
      smoking and aspirin ingestion.
AB  - Cigarette smoking is a known risk factor for cardiovascular disease in men and
      women, and it has been suggested that this risk is linked to enhanced formation
      of platelet thromboxane A2 (TxA2). This led us to investigate the effect of
      cigarette smoking and TxA2 formation on collagen-induced thrombogenesis in
      flowing nonanticoagulated human blood. Thrombus formation in blood from smokers
      and nonsmokers was compared before and 2 hours after ingestion of a single oral
      dose of 990 mg aspirin, which is sufficient to block platelet TxA2 formation.
      Nonanticogulated blood was drawn directly from an antecubital vein over collagen
      fibrils in a parallel-plate perfusion chamber by a peristaltic roller pump placed
      distally to the chamber. Wall shear rates at the collagen surface were
      characteristic for medium-sized (650 s-1) and moderately stenosed (2600 s-1)
      arteries. Blood-collagen interactions were morphologically quantified, and
      markers of platelet release, beta-thromboglobulin (beta-TG), and activation of
      coagulation, fibrinopeptide A (FPA), were measured immediately distal to the
      perfusion chamber. The thrombus volume in blood from cigarette-smoking
      individuals was nearly twofold larger than in blood from nonsmokers at 2600 s-1
      (37.4 and 19.4 microns 3/microns 2; P < .03). However, ingestion of aspirin
      reduced the thrombus volume in blood from smokers by 61.8% (P < .01), which was
      substantially more than the 37.6% reduction in blood from nonsmokers (P < .03).
      Neither cigarette smoking nor aspirin ingestion affected thrombus formation at
      650 s-1. The plasma levels of FPA and beta-TG were slightly lower in nonsmokers
      and after aspirin ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148360
TI  - Liposome-like particles isolated from human atherosclerotic plaques are
      structurally and compositionally similar to surface remnants of triglyceride-rich
      lipoproteins.
AB  - Recent studies have demonstrated the presence of unesterified cholesterol-rich,
      liposome-like vesicles in the extracellular space of atherosclerotic lesions in
      humans and animals. Liposome-like vesicles accumulate in the subendothelial space
      in rabbits within 2 weeks of initiation of cholesterol feeding, well before foam
      cells appear. These observations suggest that extracellular liposome-like
      vesicles may play a pivotal role in atherogenesis. The origin of these particles
      is unknown. We report a combination of in vivo and in vitro experiments that
      suggest a novel origin for these liposome-like vesicles. We demonstrate that the
      liposome-like particles isolated from postmortem human atherosclerotic plaques
      are rich in intact apolipoprotein (apo) A-I, C apolipoproteins, and
      sphingomyelin. We show that the in vivo derived particles are virtually
      identical, structurally and compositionally, to liposome-like lipolytic surface
      remnants of triglyceride (TG)-rich lipoproteins produced during in vitro
      lipolysis of hypertriglyceridemic serum. In vitro lipolysis of isolated very-low
      density lipoprotein has shown that the lipolytic surface remnants remain attached
      to the core remnants in the absence of high-density lipoprotein (HDL), dissociate
      to form liposome-like vesicles in the presence of low levels of HDL, and are
      assimilated into HDL to form larger HDL particles in the presence of excess HDL.
      Thus, the in vitro produced, liposome-like particles represent a complex of
      lipolytic surface remnants of TG-rich lipoproteins and apo A-I derived from HDL.
      Two possible origins have been suggested for the extracellular liposome-like
      vesicles in atherosclerotic plaques: (1) modified, aggregated, and/or degraded
      LDL particles entrapped in an intimal matrix and (2) intracellular lipid products
      of arterial wall cells. Neither possibility directly explains the presence of A-I
      and C apolipoproteins and excess sphingomyelin that we observe. We propose as an
      alternate explanation that the in vivo liposome-like particles are lipolytic
      surface remnants of TG-rich lipoproteins. We further suggest that these remnants
      are produced in the intimal space by undefined processes and/or are transcytosed
      into the intima from the plasma compartment as a product of normal lipolysis gone
      awry. We conjecture that one role of HDL may be to assimilate the highly
      atherogenic liposome-like particles in a (1) "mop-up" fashion to remove them from
      the artery wall and/or (2) preventive fashion in the plasma compartment to
      prevent their transcytosis into the artery wall. The suggestion that elevated
      concentrations of surface remnants act as a "sink" for apo A-I can also account
      for the well-established but poorly understood link between hypertriglyceridemia
      and low HDL.

PMID- 8148361
TI  - Effect of flow on the process of endothelial cell division.
AB  - In this study we investigated the effect of flow and the associated shear stress
      on the process of endothelial cell division. A shear stress of 7 N/m2 (70
      dyne/cm2) was applied to a monolayer of bovine aortic endothelial cells (BAECs)
      by using a parallel-plate flow-chamber system. Dividing cells under flow
      conditions were qualitatively compared with those under static-culture
      conditions. In addition, the duration of some phases of the cell cycle (ie,
      mitosis and cytokinesis) was measured for both static and flow conditions.
      Dividing BAECs in static cultures bowed upward; however, when cells were
      preconditioned by at least 6 hours of exposure to flow, they stayed relatively
      attached to the substrate during the entire process of cell division. Cell area
      significantly decreased during division for both static-culture and flow
      conditions. Finally, although significant changes in the duration of phases were
      observed in single experiments during which cells were exposed to shear stress,
      any differences disappeared when the data for a large number of cells were
      combined. Hence, on average, flow and its associated shear stress did not affect
      the duration of the different phases of endothelial cell division.

PMID- 8148362
TI  - Structural organization of reconstituted human arterial smooth muscle tissue.
AB  - We used human arterial smooth muscle cells (SMCs) that had been reorganized three
      dimensionally into aggregates, so-called spheroids, as a model system that might
      more closely correspond to arterial smooth muscle in vivo than do conventional
      monolayer cultures. After reaggregation the presence of serum in the culture
      medium strongly promoted the maintenance of spheroidal SMCs. With access to fresh
      serum, the spheroids developed into highly organized structures with an outer
      laminated shell of spindle-shaped SMCs and a more porous core of rounded or
      polygonal SMCs. After several weeks in culture, extracellular matrix components
      appeared and the tissue assumed features characteristic of maturing intimal
      repair tissue. Many cells had features of programmed cell death (apoptosis). This
      feature may be important because it may indicate that regression of arterial
      smooth muscle tissue may be a much more strongly controlled process than hitherto
      realized. Without access to fresh serum, the spheroidal tissue showed
      degenerative features, much like those in atherosclerotic lesions, ie, the
      presence of foam cells, cellular debris, and some cell death. It is possible that
      this situation in vitro resembles that of atherosclerotic tissue in vivo, in
      which retention of plasma constituents is a conspicuous feature. In some
      respects, therefore, the small sample of human arterial tissue represented by the
      spheroid may represent an in vitro analogue of the arterial wall, which may
      undergo maturation or degenerative atherosclerosis-like changes depending on
      exogenous factors. The spheroidal SMC system may therefore also be a suitable
      model for in vitro studies of atherogenesis.

PMID- 8148363
TI  - Pharmacology of benzodiazepine receptors: an update.
AB  - Benzodiazepine receptors are allosteric modulatory sites on GABAA receptors.
      GABAA receptors are probably composed of five protein subunits, at least some of
      which belong to different subunit classes. So far six alpha-, four beta-, three
      gamma-, and delta- and two rho = p subunits of GABAA receptors have been
      identified. A large number of different subunit combinations, each of which will
      result in a GABAA receptor with distinct electrophysiological and pharmacological
      properties, are therefore possible. Many compounds from different chemical
      classes which are able to bind to benzodiazepine receptors have been identified.
      Depending on their individual efficacy, binding of these compounds either
      enhances, reduces or does not influence GABAergic transmission. However, the
      individual efficacy of the benzodiazepine receptor ligands changes with the
      subunit composition of the GABAA receptor. The investigation of the regional
      distribution, subunit composition and pharmacology of GABAA receptors will result
      in the development of new and more selective compounds for psychiatry.

PMID- 8148364
TI  - Polymorphism in the metabolism of drugs, including antidepressant drugs: comments
      on phenotyping.
AB  - In neurochemistry there are advantages in determining how patients are likely to
      react to psychoactive drugs prior to the commencement of drug therapy.
      Explanations of a patient's nonresponse, or unexpected adverse reactions to drugs
      are required. In many instances, a knowledge of the drug metabolism status of a
      patient can be helpful in the selection of a drug and its dosage regimen, and in
      the prediction of possible drug/drug interactions when two or more drugs have to
      be administered concomitantly. Important information on these topics may be
      obtained by phenotyping patients prior to drug therapy. The metabolism of various
      antidepressant and neuroleptic drugs is catalyzed by CYP2D6, a cytochrome P450
      isozyme (also named P450IID6), whereas the metabolism of other drugs may involve
      different cytochromes P450. The properties of CYP2D6 and four other isozymes
      (CYP1A1, CYP1A2, CYP2C8/9 and CYP3A4) are described, and substrates identified.
      Phenotyping of patients for CYP2D6 activity and mephenytoin hydroxylase activity
      is described.

PMID- 8148365
TI  - Angiotensin converting enzyme inhibitors as potential cognitive enhancing agents.
AB  - Anecdotal reports of a mood-elevating effect in patients and improvements in the
      performance of memory tests in the clinic has led to investigations into the
      nootropic actions of angiotensin converting enzyme (ACE) inhibitors. A cognitive
      enhancing action for the ACE inhibitors has been demonstrated in a number of
      animals models of memory function. Neurochemical studies in animals have shown
      that angiotensin II acting via an angiotensin II receptor can inhibit the release
      of 3HAch from entorhinal cortex slices. Thus the ability of ACE inhibitors to
      facilitate cognitive processes may be related to reduced availability of
      angiotensin II. Lack of specificity of ACE inhibitors may be a limiting factor in
      the development of such compounds as cognitive enhancers. However, the recent
      development of selective antagonists for subtypes of the angiotensin II receptor
      may represent a novel approach for the treatment of cognitive disorders with an
      underlying cholinergic disturbance.

PMID- 8148366
TI  - Curative effects of the atypical antidepressant mianserin in the chronic mild
      stress-induced anhedonia model of depression.
AB  - This study was designed to validate a novel animal model of depression by testing
      the curative effects of the atypical antidepressant mianserin. In this paradigm,
      the hedonic state of rats was assessed using an intracranial self-stimulation
      (ICSS) procedure. The ICSS threshold was determined before, during and after a 38
      day period of exposure to a variety of intermittent, unpredictable, mild
      stressors. After 11 days of this regimen, the ICSS threshold was significantly
      higher in the stressed rats, suggesting a gradual decrease of sensitivity to
      reward. This "anhedonia" lasted throughout the stress regimen and progressively
      diminished over a 20-day period after stress was terminated. When stressed
      animals exhibiting anhedonia were treated with mianserin, the stress-induced
      increase in the ICSS threshold was gradually reversed over ten days of treatment.
      These results provide further support for the value of this anhedonia paradigm in
      modelling an important aspect of human depressive disorders.

PMID- 8148367
TI  - 4-Ethoxyamphetamine: effects on intracranial self-stimulation and in vitro uptake
      and release of 3H-dopamine and 3H-serotonin in the brains of rats.
AB  - Experiments were conducted to compare the effects of 4-ethoxyamphetamine, a novel
      "designer" amphetamine, with (+)-amphetamine and an earlier "designer"
      amphetamine, 4-methoxyamphetamine, on rats. (+)-Amphetamine significantly
      decreased frequency threshold measures in an intracranial self-stimulation (ICSS)
      procedure using medial forebrain bundle electrodes, while 4-methoxyamphetamine
      and 4-ethoxyamphetamine increased these ICSS frequency thresholds. 4
      Methoxyamphetamine and 4-ethoxyamphetamine had more potent effects on inhibition
      of uptake and stimulation of spontaneous release of 5-hydroxytryptamine
      (serotonin) than of dopamine. It is concluded that the neuropsychopharmacological
      profile of 4-ethoxyamphetamine is unlike that of (+)-amphetamine, but similar to
      that of 4-methoxyamphetamine, a potent hallucinogen in humans.

PMID- 8148368
TI  - Effects of repeated treatment with fluoxetine and citalopram, 5-HT uptake
      inhibitors, on 5-HT1A and 5-HT2 receptors in the rat brain.
AB  - Repeated treatment with fluoxetine and citalopram, which are potent 5-HT reuptake
      inhibitors, resulted in different regulation of 5-HT1A and 5-HT2 receptors in the
      rat brain. Their effects were compared with those of other antidepressants:
      imipramine, mianserin and levoprotiline. The density of 5-HT1A receptors,
      labelled with [3H]8-OH-DPAT, in the rat hippocampus was enhanced after
      citalopram, imipramine, mianserin and levoprotiline, but not altered after
      fluoxetine administration. [3H]Ketanserin binding sites, which label 5-HT2
      receptors, were increased after fluoxetine and levoprotiline, but decreased after
      citalopram, imipramine and mianserin in the rat cerebral cortex. Acute
      administration of fluoxetine, but not citalopram, resulted in a decreased density
      of 5-HT1A receptors. 5-HT2 receptors were not changed by acute administration of
      either fluoxetine or citalopram. The obtained results indicate that besides 5-HT
      reuptake inhibiting properties of both compounds, there may exist an additional
      mechanism(s) of their action, which leads to different regulation of 5-HT1A and 5
      HT2 receptors.

PMID- 8148369
TI  - Recent developments in the initiation of chromosomal DNA replication: a complex
      picture emerges.

PMID- 8148370
TI  - Molecular cloning and characterization of an isoprenylated 67 kDa protein.
AB  - The cDNA coding for a 67 kDa protein (p67) was isolated from a rat Schwann cell
      library. A recombinant form of p67 expressed in bacteria was used to produce
      polyclonal anti-p67 antibodies. By immunoblot analysis p67 was found to be
      expressed in most tissues and cell lines examined. Inspection of the deduced
      amino acid sequence revealed a COOH-terminal consensus sequence for
      isoprenylation. Consistent with this finding, p67 was a substrate for
      isoprenylation in vitro by geranylgeranylpyrophosphate. p67 was associated
      predominantly with the particulate fraction of rat smooth muscle cells. The rat
      p67 sequence was highly homologous to a family of recently described human and
      mouse gamma-interferon inducible, guanine nucleotide binding proteins.

PMID- 8148371
TI  - Interactions among four subunits of elongation factor 1 from rice embryo.
AB  - To establish the subunit construction of elongation factor EF-1, interactions
      among four non-identical subunits of rice embryo EF-1 (alpha, beta, beta', and
      gamma) were analyzed with polyacrylamide gel electrophoresis. Complexes beta
      beta', alpha beta, alpha beta', and beta gamma were formed by mixing the two
      respective subunits. However, no complex was formed between EF-1 beta' and EF-1
      gamma. Complexes containing three subunits like alpha beta beta', alpha beta
      gamma, and beta beta' gamma, were formed by mixing the three respective subunits.
      EF-1 was reconstructed when each subunit was added in the following order, beta,
      beta', gamma, and alpha. The affinity of EF-1 alpha for other subunits was as
      follows, beta beta' gamma > beta beta' > beta not equal to beta'. Likewise, the
      affinity of EF-1 gamma for other subunits was: beta beta' gamma > beta >> beta'.
      Phe-tRNA binding activity of the reconstructed EF-1 was about 90% of that of the
      native EF-1. From these results, we concluded that rice embryo EF-1 is
      constructed of equimolar amount of four subunits, alpha, beta, beta' and gamma.

PMID- 8148372
TI  - Coordinated expression and mechanism of induction of HSP32 (heme oxygenase-1)
      mRNA by hyperthermia in rat organs.
AB  - Heme oxygenase isozymes, HO-1 and HO-2, catalyze the cleavage of heme b (Fe
      protoporphyrin-IX) at the alpha-meso carbon bridge to form the antioxidant,
      biliverdin IX alpha, and the putative cellular messenger, carbon monoxide. HO-1
      is a heat shock (HSP32) or stress protein, while HO-2 is a noninducible enzyme.
      Presently, we have examined the time course of expression of HSP32 in liver,
      kidney, and heart of rats exposed to hyperthermia and investigated the mechanism
      of induction of HO-1 by hyperthermia. We report a coordinated induction response
      of all organs to elevated ambient temperature (42 degrees C, 20 min).
      Specifically, the maximum induction of the 1.8 kb HO-1 mRNA was observed 1 h
      after hyperthermia and reached a value 20-40-fold that of the control; the
      transcript level approximated the control value by 6 h after heat stress. In
      contrast, the levels and the ratio of the 1.3 and 1.9 kb HO-2 transcripts were
      not affected by hyperthermia. As judged by in vitro nuclear transcription run-on
      assays, thermal stress caused the stimulation of HO-1 gene transcription. The
      increase in HO-1 mRNA transcription was accompanied by an increase in binding of
      nuclear factor(s) to the heat shock element in the promoter region of the gene.
      The increase of the HO-1 mRNA was reflected in increases in both heme oxygenase
      activity and in immunoreactive HO-1 protein. We suggest that the induction of
      heme oxygenase by heat stress is a physiologically relevant defense mechanism
      whereby both the degradation of heme of denatured hemoproteins and the generation
      of biologically active products of heme catabolism are enhanced.

PMID- 8148373
TI  - Localization of c-myc protooncogene expression in the rat heart in vivo and in
      the isolated, perfused heart following treatment with norepinephrine.
AB  - We have investigated the expression of the protooncogene c-myc in rat hearts
      following exposure to norepinephrine, both in vivo and in isolated perfused
      preparations. Both chronic and acute norepinephrine treatment produced a rapid,
      transient elevation of c-myc mRNA in adult rat hearts, but chronic infusion
      produced a second, larger increase. This expression profile was characteristic
      for c-myc since it was not found for four other protooncogenes. In the isolated,
      perfused heart, addition of norepinephrine to the perfusion buffer and elevation
      of perfusion pressure separately increase c-myc mRNA suggesting both direct
      hormonal and hemodynamic factors might be important in vivo. Immunocytochemistry
      showed that Myc protein accumulated predominantly in the nuclei of non-myocyte
      cells following norepinephrine treatment indicating that expression at the mRNA
      level culminated in protein synthesis. These findings suggest that the c-myc
      expression observed in the hypertrophying adult heart following exposure to
      norepinephrine may be associated with proliferating cells like fibroblasts rather
      than cardiomyocytes.

PMID- 8148374
TI  - The giant extracellular hemoglobin from the polychaete Neanthes diversicolor. The
      cDNA-derived amino acid sequence of linker chain L2 and the exon/intron boundary
      conserved in linker genes.
AB  - The 4000 kDa extracellular hemoglobin from the polychaete Neanthes diversicolor
      consists of three types of subunits; three 15 kDa monomers (chains M1, M2 and
      M3), a 45 kDa disulfide-bonded trimer of chains T1, T2 and T3, and two 50-55 kDa
      disulfide-bonded homodimeric linkers (chains L1 and L2). The latter linker
      subunits are essential for the assembly of the other heme-containing subunits,
      monomers and a trimer. The cDNA encoding the linker chain L2 was amplified by
      polymerase chain reaction (PCR), and the cDNA-derived amino acid sequence of 235
      residues has been determined. The sequence showed 22-75% identity with other
      linker chains. All of the linker sequences examined so far have a highly
      conserved cysteine-rich segment at positions 89-130: Xaa3-Cys-Xaa6-Cys-Xaa6-Cys
      Xaa6-Cys-Asp-Gly-X aa2-Asp-Cys-Xaa4-Asp-Glu-Xaa4-Cys, and the motif corresponds
      exactly to the cysteine-rich repeats of the ligand-binding domains of vertebrate
      low-density lipoprotein (LDL) receptors (Suzuki, T. and Riggs, A.F. (1993) J.
      Biol. Chem. 268, 13548-13555). A 287 bp intron interrupts the coding sequence of
      Neanthes L2 gene just at the N-terminal boundary of this motif, and the position
      of the splice junction was exactly conserved in Neanthes and Lumbricus linker
      genes. This suggests that the intron has been conserved for at least 450 million
      years in annelid linker genes. The evolutionary origin of the remaining parts of
      linker chains is unclear, but it is noteworthy that the topology of the two
      intrachain disulfide bridges in the C-terminal segment of linker chains is
      homologous with that of the carbohydrate-recognition domain of animal C-type
      lectin.

PMID- 8148375
TI  - Characterisation of functional domains within the mouse erythropoietin 3'
      enhancer conveying oxygen-regulated responses in different cell lines.
AB  - We have analysed sequences within the mouse erythropoietin enhancer which are
      required for oxygen regulated operation in the erythropoietin producing cell
      line, HepG2, and in two non-erythropoietin producing cell lines; the lung
      fibroblastoid cell line a23, and mouse erythroleukaemia (MEL) cells. At least
      three critical sites were demonstrated within a 96 nucleotide sequence. Oxygen
      regulated operation was dependent on sites within the first 26 nucleotides.
      Sequences lying 3' to this region modulated enhancer function but did not
      themselves convey oxygen regulated operation. In HepG2 cells these 3' sequences
      co-operated to permit operation of the inducible element at a distance from a
      promoter, but in MEL cells 3' sequences repressed activity of the inducible
      element. Though operation of this 3' sequence differed according to the cell
      type, oxygen regulated operation was dependent on the same two critical sites in
      the 5' region in both erythropoietin producing and non-erythropoietin producing
      cells. These findings support the existence of a widespread oxygen sensing system
      in mammalian cells which is similar to that operating in specific cells to
      regulate erythropoietin production, and they indicate that the system activates
      factors with similar DNA sequence specificity in different cells.

PMID- 8148376
TI  - Organization of the mouse GP42/Basigin gene: a member of the Ig superfamily.
AB  - We have mapped and sequenced the GP42/Basigin gene isolated from a Balb/C mouse
      genomic library. The genomic organization and upstream, putative regulatory,
      regions of this gene have not been previously reported. Our data show that exon 5
      of the GP42/Basigin gene encodes the carboxy proximal half of the second Ig-like
      domain, the highly conserved transmembrane region and a portion of the
      cytoplasmic tail. This inclusion of Ig-like and other functional domains in a
      single exon is unusual. Splice junction analysis indicates that two reported
      alternate GP42/Basigin cDNA isoforms are likely due to cloning artifacts. In
      addition, we find that GP42/Basigin is polymorphic in mice. Our data also support
      the proposal that the transmembrane domain and portions of the cytoplasmic region
      of GP42/Basigin have been evolutionarily conserved.

PMID- 8148377
TI  - Molecular cloning of the murine homologue of CD63/ME491 and detection of its
      strong expression in the kidney and activated macrophages.
AB  - The mouse homologue of CD63/ME491 (Mu-CD63) was molecularly cloned and analyzed.
      Mu-CD63 exhibited a strikingly high similarity to CD63/ME491 and the rat
      homologue. Northern blot analysis revealed that Mu-CD63 mRNA was expressed
      strongly in the kidney of adult mice, especially in the glomerulus fraction,
      implying the possibility that Mu-CD63 plays an important role in maintaining
      normal renal function. Activated macrophages and splenocytes exhibited strong
      expression of Mu-CD63 mRNA, whereas cultured thymocytes barely expressed the mRNA
      irrespective of cell activation. Taken together, the present results suggest that
      Mu-CD63 expression is associated with differentiation and/or development of
      certain cell types, but not necessarily with cell proliferation.

PMID- 8148378
TI  - Molecular cloning and functional analysis of a cDNA coding for human DOPAchrome
      tautomerase/tyrosinase-related protein-2.
AB  - We have cloned the cDNAs encoding tyrosinase-related protein-2 (TRP-2) from a
      human melanoma cDNA library. Transient expression of the isolated cDNA in HeLa
      cells established that TRP-2 is DOPAchrome tautomerase. Human TRP-2/DOPAchrome
      tautomerase is composed of 519 amino acids with a molecular weight of 59,000 and
      has about 84% identity with the mouse counterpart.

PMID- 8148379
TI  - A novel actin cDNA is expressed in the neurons of Aplysia californica.
AB  - A novel actin cDNA has been isolated from an abdominal ganglion cDNA library of
      Aplysia californica by differential screening. This cDNA of 1596 nucleotides in
      length encodes a putative actin protein of 41.8 kDa. This protein shows 95.2%
      identity with another Aplysia actin gene previously shown to be expressed in the
      muscular sheath of the ganglion (DesGroseillers et al. (1990) Nucleic Acids Res.
      18, 3654). However, the 5' and 3' untranslated regions of these cDNAs are
      completely different. PCR experiments performed with mRNA isolated from dissected
      neurons, ovotestis or kidney reveal that the gene is expressed in the neurons of
      the ganglia and in other tissues as well. Southern blot analysis reveals that the
      neuronal actin gene is a member of a large gene family.

PMID- 8148380
TI  - Cloning and sequencing of a cDNA encoding the murine vitamin K-dependent protein
      S.
AB  - A cDNA clone encoding the vitamin K-dependent protein S was isolated from a
      murine liver cDNA library. Sequencing revealed an open reading frame encoding a
      634 amino acid mature protein. Comparison to human and bovine sequences showed a
      high degree of similarity and the conservation of key residues between the
      species.

PMID- 8148381
TI  - Cloning and nucleotide sequence of a full length cDNA encoding ribosomal protein
      L27 from human fetal kidney.
AB  - Differential screening of a human fetal kidney cDNA library resulted in the
      isolation of D69, eventually renamed HumRPL27, which was expressed at higher
      levels in fetal kidney than in adult kidney. The 476 bp cDNA insert from HumRPL27
      contains an open reading frame of 135 amino acids displaying 100% identity to rat
      RPL27 and chicken RPL27 predicted protein sequences although 64 and 38 silent
      base pairs changes respectively are found at the DNA level. In Northern blots, a
      1.0 kb HumRPL27 mRNA transcript is expressed abundantly in all fetal tissues
      examined and at lower abundance in adult tissues. Southern analysis of HumRPL27
      suggests the presence of multiple copies of the gene in human, rat, mouse and
      hamster DNA.

PMID- 8148382
TI  - The nucleotide sequence of the gene coding for the elongation factor 1 alpha in
      Sulfolobus solfataricus. Homology of the product with related proteins.
AB  - The cloning and sequencing of the gene coding for the archaebacterial elongation
      factor 1 alpha (aEF-1 alpha) was performed by screening a Sulfolobus solfataricus
      genomic library using a probe constructed from the eptapeptide KNMITGA that is
      conserved in all the EF-1 alpha/EF-Tu known so far. The isolated recombinant
      phage contained the part of the aEF-1 alpha gene from amino acids 1 to 171. The
      other part (amino acids 162-435) was obtained through the amplification of the S.
      solfataricus DNA by PCR. The codon usage by the aEF-1 alpha gene showed a
      preference for triplets ending in A and/or T. This behavior was almost identical
      to that of the S. acidocaldarius EF-1 alpha gene but differed greatly from that
      of EF-1 alpha/EF-Tu genes in other archaebacteria eukaryotes and eubacteria. The
      translated protein is made of 435 amino acid residues and contains sequence
      motifs for the binding of GTP, tRNA and ribosome. Alignments of aEF-1 alpha with
      several EF-1 alpha/EF-Tu revealed that aEF-1 alpha is more similar to its
      eukaryotic than to its eubacterial counterparts.

PMID- 8148383
TI  - Sequencing of a cDNA encoding the human fast-twitch skeletal muscle isoform of
      troponin I.
AB  - A cDNA encoding the human fast-twitch skeletal muscle isoform of troponin I
      (TnIfast) has been sequenced. This cDNA is 701 base pairs in length, and encodes
      a protein of 182 amino acids. TnIfast is the last of the three known human TnI
      isoforms to be sequenced. Comparison of the deduced human TnIfast protein
      sequence with a variety of troponin I isoforms from other species has revealed a
      high degree of cross-species sequence conservation between TnIfast proteins.

PMID- 8148384
TI  - Formation of a hairpin structure by telomere 3' overhang.
AB  - The telomeres of most eukaryotes contain tandemly-repeated DNA sequences, with a
      cluster of G residues on one strand. Recent studies showed that the Oxytricha
      telomeric DNA oligonucleotide, d(G4T4G4), dimerizes to form a quadruplex in the
      presence of Na+ or K+. We have observed that the oligonucleotide d(G4T4G4) does
      not dimerize in the presence of Li+ ion at low sample concentrations. In the
      monomeric state, this molecule forms a simple foldback hairpin structure
      containing G x G reverse Hoogsteen basepairs in the stem region. This hairpin
      structure has a thermal stability which is well reconciled with telomere
      functions in vivo.

PMID- 8148385
TI  - Isolation of promoter for cytosolic phospholipase A2 (cPLA2).
AB  - Cytosolic phospholipase A2 (cPLA2) releases arachidonic acid from membrane
      phospholipids and is believed to be the rate-limiting enzyme in the arachidonic
      acid pathway. We report herein the isolation of a 3 kb fragment of rodent genomic
      DNA containing part of the first intron, the first exon and 5'-flanking sequence.
      The start site of transcription was mapped by 5'-rapid amplification of cDNA ends
      and corroborated by ribonuclease protection assay. The gene has a TATAless
      promoter with no classical Sp1 binding sites or initiator element. A
      microsatellite series of CA repeats was noted in the 5'-flanking region of both
      the rodent and human promoters. Deletion constructs have been analysed for
      luciferase activity and confirmed promoter activity.

PMID- 8148386
TI  - Dexamethasone-dependent modulation of human lymphoblastoid B cell line through
      sphingosine production.
AB  - The relationship between dexamethasone-dependent changes in intracellular
      sphingosine levels, energy and phospholipid metabolism have been investigated by
      31P-NMR spectroscopy and high-performance liquid chromatography. The cellular
      functions have been evaluated by cellular growth and immunoglobulin M secretion
      (IgM). Significant increases in intracellular phosphorylcholine (PCho),
      extracellular choline (Cho), and endogenous sphingosine levels were observed only
      at 30 min incubation with dexamethasone. These results confirmed a sphingosine
      dependent hydrolysis of choline-linked phospholipids (Miccheli, A., Ricciolini,
      R., Piccolella, E., Delfini, M. and Conti, F. (1991) Biochim. Biophys. Acta 1093,
      29-35). Furthermore, no significant variations were evidenced at hours 1, 2, 6
      and 18 of incubation. Dexamethasone causes an inhibition of cellular growth and
      IgM secretion as well as the sphingosine treatment. The results suggest that the
      effect of dexamethasone may be mediated by endogenous sphingosine production in
      Epstein-Barr virus transformed B lymphocytes.

PMID- 8148387
TI  - Seminal plasmin, a bovine seminal plasma protein, lyses dividing but not resting
      mammalian cells.
AB  - Seminal plasmin, an antimicrobial and transcription-inhibitory protein of bovine
      seminal plasma, is shown to lyse dividing mammalian cells in vitro. It lyses
      cells in culture such as CHO, Vero, HeLa and L929. It also lyses regenerating rat
      liver parenchymal cells and cells of two ascitic tumours of rat--the Zajdela
      ascitic hepatoma and the AK-5. However, it does not lyse resting cells such as
      adult liver parenchymal cells, erythrocytes, or resting lymphocytes, though it
      binds to their cell surface. It can be used, therefore, to distinguish cells that
      are in the division cycle from cells that are in the resting phase. The cell
      lytic activity of seminal plasmin is inhibited by Ca2+.

PMID- 8148388
TI  - Inhibition of the G1-S transition of the cell cycle by inhibitors of
      deoxyhypusine hydroxylation.
AB  - The formation of the unusual amino-acid hypusine in eIF-5A (eukaryotic initiation
      factor 5A) is associated with cellular proliferation. We used a panel of
      compounds, including mimosine, to probe the relationship between the exit from
      the G1 phase of the cell cycle, i.e., the onset of DNA replication, and the
      formation of hypusine by the enzyme deoxyhypusyl hydroxylase (DOHH). These two
      parameters displayed the same dose dependency and structure-activity
      relationship. Only compounds that inhibited DOHH also suppressed proliferation.
      This effect was observed: (i) in spontaneously proliferating, virally
      transformed, and mitogen-stimulated cells; (ii) for both anchorage-dependent and
      anchorage-independent proliferation; and (iii) with normal and malignant cell
      lines. DOHH reactivation occurred rapidly after inhibitor withdrawal and
      correlated with synchronized entry into S. The changes in the expression of
      specific genes during the G1-to-S transition mimicked the physiological pattern.
      These findings suggest that hypusine formation in eIF-5A which occurs in a
      specific, invariant sequence motif acquired early in evolution, may be involved
      in the G1-to-S transition in the eukaryotic cells tested.

PMID- 8148389
TI  - The nonapeptide leucinostatin A acts as a weak ionophore and as an
      immunosuppressant on T lymphocytes.
AB  - Earlier studies have disclosed that leucinostatin A, a hydrophobic nonapeptide
      antibiotic, assumes an alpha-helical secondary structure in nonpolar
      environments. The present report demonstrates that the peptide acts as a weak
      ionophore facilitating the transport of mono-and divalent cations through the
      plasma membrane of T lymphocytes and through artificial membranes. Leucinostatin
      A does not change the thymidine uptake of both resting mouse thymocytes and
      peripheral blood lymphocytes but dose-dependently prevents the activation of T
      lymphocytes by tetradecanoyl-phorbol-acetate and by anti-T cell receptor
      antibody.

PMID- 8148390
TI  - Intracellular sodium in cardiomyocytes using 23Na nuclear magnetic resonance.
AB  - Intracellular sodium content in superfused isolated rat cardiomyocytes was
      measured using 23Na nuclear magnetic resonance. The shift reagent dysprosium
      tripolyphosphate was added to the buffer to distinguish between NMR signals from
      the intracellular region and the extracellular buffer. The NMR visibility of the
      intracellular sodium signal was experimentally determined by measuring the
      changes induced in the sodium NMR signals by application of ischemia as an
      intervention. Intracellular volume was accounted for by determining the change in
      the sodium signal upon adding cells (in beads) to the buffer solution at the
      beginning of each experiment and by killing the cells (in beads) with Triton X
      100 at the end of each experiment. The visibility of intracellular sodium
      (relative to extracellular) was 0.47 +/- 0.12 (mean +/- S.D., n = 12). The
      average intracellular sodium concentration using this visibility is 29 +/- 4.5 mM
      (n = 12). This value is much higher than results obtained by some investigators
      using NMR techniques and by others using different standard methods, with the
      exception of those methods which evaluate the total intracellular sodium (atomic
      absorption spectroscopy and X-ray microanalysis). We conclude that total Nai is
      higher than generally reported, using other accepted techniques such as ion
      specific electrodes, and that 23Na-NMR analysis can be used to accurately
      determine Nai in intact cells.

PMID- 8148391
TI  - Modulation of proliferation of cultured human cells by urinary trypsin inhibitor.
AB  - Several reports have indicated that proteinase inhibitors can act as both
      stimulators and inhibitors of the growth of cultured cells. To confirm and extend
      these reports, we have purified the trypsin inhibitor from human urine (UTI). We
      have demonstrated a biphasic effect of this protein on the proliferation of human
      fibroblasts, and have identified two types of cellular binding site which may be
      responsible for the stimulatory and inhibitory aspects of this effect. Both
      aspects of UTI action have also been observed in human tumour cell cultures, but
      they are not consistently associated in these cells.

PMID- 8148392
TI  - Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus
      protein A.
AB  - Peptides from 10 to 22 amino acids containing sequences encompassed by
      Staphylococcus aureus protein A were synthesized. Some of these peptides, when
      present in cultures of lymphomononuclear cells from healthy donors or from cancer
      patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell
      carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear
      population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and
      (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated
      monocytes responded also to those peptides with a release of IL-1 and TNF alpha
      and an increase of cytotoxicity against HT-29 cells. It was found that the active
      peptides had the following structural pattern: a length of at least 15 amino-acid
      residues with a proline at position 6, valine, leucine, isoleucine, glycine,
      alanine or lysine at position 2, and glutamic or aspartic acid at position 11.
      Replacement of Pro at position 6 with any other residue turned the peptide
      inactive. Replacement of residues at positions 2 and 11 with amino-acid residues
      other than those required for activity resulted in compounds with a marked
      decrease in the immunomodulating properties described, or lacking these
      properties altogether.

PMID- 8148393
TI  - Vitamin D stimulates DNA synthesis in alveolar type-II cells.
AB  - Alveolar type-II cells are responsible for alveolar epithelial cell proliferation
      during growth and development and in response to lung injury. Based on the
      observation of abnormal lung development in rachitic rat pups and the expression
      of receptors for vitamin D by fetal alveolar epithelial cells, the present study
      examined the influence of 1,25-dihydroxy vitamin D (DHD) on the proliferation of
      primary cultures of fetal, neonatal and adult alveolar epithelial cells. The
      ontogony of vitamin D responsiveness was examined, using fetal (days 18, 19 and
      22 = term), neonatal (days 7 and 18) alveolar epithelial cells as well as adult
      alveolar type-II cells. Maximal stimulation of [3H]thymidine incorporation
      occurred in neonatal d18 cells: (250 +/- 4.8%, n = 4, P < 0.05). Incubation of
      adult type-II cells, in the presence of 10(-9) M DHD increased thymidine
      incorporation into DNA (149.1 +/- 33.2%, mean +/- S.E., n = 3, P < 0.001)
      compared to control cells maintained in basal medium. Exposure to DHD also
      increased thymidine incorporation after stimulation with a mixture of
      conventional progression factors (insulin (10 micrograms/ml) (I), cholera toxin
      (10 micrograms/ml) (C) and EGF (20 ng/ml) (E)) (349.4 +/- 42.9% vs. 213.5 +/-
      23.6%, n = 6, P < 0.005). Autoradiographic labeling indices of adult type-II
      cells increased from 3.1 +/- 0.6% for cells cultured in basal medium to 7.2 +/-
      1.7% in cells exposed to DHD from the time of plating and I, C, E from 20-68 h in
      culture (n = 4, P < 0.05). Although no increase in the number of adult type-II
      cells was observed in these experiments, flow cytometric analysis of nuclear DNA
      content revealed an increased proportion of cells in the S and G2 phases of the
      cell cycle (basal: S = 2.6%, G2/M = 3.0%, DHD+GF: S = 4.7%, G2/M = 5.6%, P < 0.05
      for each comparison). These data demonstrate that vitamin D3 is a growth factor
      for alveolar type-II cells and suggest the possibility that local elaboration of
      vitamin D may provide a novel mechanism of modulation of epithelial proliferation
      in the context of lung development and repair.

PMID- 8148394
TI  - Role of extracellular calcium in the regulation of 1,25-dihydroxyvitamin D3
      formation in cultured human keratinocytes.
AB  - Cultured normal human keratinocytes (NHK) provide a useful experimental model for
      studies of processes occurring during terminal differentiation, since the extent
      of keratinocyte maturation can be manipulated experimentally by modulation of
      extracellular calcium concentration. When NHK are maintained in low calcium (0.06
      mM) medium they proliferate but do not stratify. Raising the level of calcium to
      1-2 mM results within a few hours in induction of keratinocyte differentiation.
      Results of the present study show that formation of 1,25-(OH)2D3 is higher in NHK
      grown at 0.06 mM than in NHK grown at 1.6 mM calcium concentration. After 2 h
      exposure of low calcium cultures to 1.6 mM calcium the 1,25-(OH)2D3 production
      starts to decrease. On the other hand, exposure of cells cultured in 1.6 mM
      calcium medium to 0.06 mM calcium concentration induced already within 4 h an
      increase in 1,25-(OH)2D3 formation which was not accompanied by a decrease in
      cornified envelope formation. Thereby, the present study demonstrated that
      calcium can regulate 1,25-(OH)2D3 formation independently of changes in
      keratinocyte differentiation.

PMID- 8148395
TI  - Dexamethasone-dependent modulation of cholesterol levels in human lymphoblastoid
      B cell line through sphingosine production.
AB  - The effect of dexamethasone on lipid composition of Epstein-Barr virus
      transformed human B lymphocytes have been investigated by 31P- and 1H-NMR
      spectroscopy and compared to the effects due to exogenous sphingosine treatment.
      Furthermore, the effects of dexamethasone and sphingosine on membrane structure
      was evaluated by fluorimetry. No significant changes were evidenced in
      phospholipid composition and in the ratio of unsaturated to total fatty-acid
      chains. A significant increase in total cholesterol levels was evident at 30 min
      incubation with dexamethasone or sphingosine; a parallel increase in DPH
      polarization at 30 min was also demonstrated. TMA-DPH intensity measurements
      suggest a slowing of vesicular intracellular traffic due to the treatment. The
      results suggest a dexamethasone- and sphingosine-dependent inhibition of
      intracellular cholesterol transport.

PMID- 8148396
TI  - Arachidonic acid liberation induced by phosphatidic acid endogenously generated
      from membrane phospholipids in rabbit platelets.
AB  - The action of phosphatidic acid generated from membrane phospholipids on
      phospholipase A2 activation in rabbit platelets was investigated. When
      [3H]arachidonic acid-labelled platelets were treated with phorbol 12-myristate 13
      acetate (PMA) and the membranes isolated from the cells incubated at 37 degrees C
      with 50 microM CaCl2 and 50 microM guanosine 5'-O-(3-thiotriphosphate) (GTP gamma
      S), both phosphatidic acid production and arachidonic acid liberation increased
      in PMA- and GTP gamma S-concentration-dependent manners. Ethanol dose-dependently
      inhibited these responses, accompanied by the formation of phosphatidylethanol.
      Since propranolol, an inhibitor of phosphatidic acid phosphohydrolase, had no
      influence on the production of phosphatidic acid, the arachidonic acid liberated
      does not appear to be derived from diacylglycerol which may be produced from
      phosphatidic acid through the action of this enzyme. In another approach,
      treatment of [3H]arachidonic acid-labelled membranes with phospholipase D from
      Streptomyces chromofuscus induced arachidonic acid liberation as well as
      phosphatidic acid formation in time- and dose-dependent manners. The former
      response was suppressed by p-bromophenacyl bromide, a phospholipase A2 inhibitor.
      These results suggest that phosphatidic acid derived from membrane phospholipids
      potentiates phospholipase A2 activation and contributes to the amplification of
      platelet activation.

PMID- 8148397
TI  - Involvement of calmodulin in Ca(2+)-activated K+ efflux in human colonic cell
      line, HT29-19A.
AB  - The receptor-mediated agonist, neurotensin (NT) stimulated Ba(2+)- and
      charybdotoxin-sensitive 86Rb (K+) efflux in the HT29-19A colonic cell line.
      Efflux was also stimulated by ionomycin and thapsigargin and could be abolished
      by incubation with the intracellular Ca2+ chelator, BAPTA. Together, these data
      suggest a rise in [Ca2+]i is prerequisite for activation of K+ efflux in these
      cells. Comparison of the temporal profiles for NT-induced increases in [Ca2+]i
      and 86Rb efflux, however, failed to show a direct relationship between these
      parameters. The NT-stimulated increase in [Ca2+]i was transient, returning to
      baseline within 4-5 min, while efflux was sustained over a much longer period (>
      12 min). Ca(2+)-activated 86Rb efflux was inhibited by pretreatment with
      calmodulin (CaM) antagonist, W7. W7 had no effect on basal efflux, but reduced
      both NT- and IM-activated efflux up to 80%, with a Ki of 38 microM. Other CaM
      antagonist inhibited efflux with an order of potency (TFP approximately W8 > W7
      >> W5) consistent with inhibition of a CaM-dependent process. Inhibition by W7
      was not abolished by ouabain or bumetanide, indicating its effects are not
      mediated by action upon K+ uptake processes. W7 did not inhibit NT-stimulated
      125I efflux but significantly reduced efflux stimulated by the Ca2+ ionophore,
      ionomycin. NT-stimulated 86Rb+ efflux was localized to the basolateral membrane
      of HT29-19A monolayers grown on permeable supports. These data are consistent
      with the involvement of CaM in mediating Ca(2+)-dependent activation of K+
      conductance in HT29-19A colonocytes.

PMID- 8148398
TI  - Characterization of vasoactive intestinal peptide receptors in human liver.
AB  - The stoichiometric, pharmacological and molecular properties of vasoactive
      intestinal peptide (VIP) receptors have been analyzed in human liver membranes
      and compared in parallel with those in rat liver membranes. The binding of
      [125I]VIP was rapid, saturable and specific. The stoichiometric data indicated
      the presence of two classes of binding sites in both human and rat liver
      membranes with Kd values of 0.22 (human) and 0.20 (rat) nM for the high-affinity
      site, and 27.3 (human) and 3.6 (rat) nM for the low-affinity site. Tracer binding
      was displaced by structurally related peptides with an order of potency: VIP =
      PACAP-27 > helodermin > secretin in human liver, and VIP = PACAP-27 = helodermin
      > secretin in rat liver. GTP inhibited [125I]VIP binding in a dose-dependent
      manner suggesting the involvement of a G protein in the signal transduction
      pathway. Cross-linking experiments revealed an apparent molecular mass for the
      VIP-receptor complex that was 67,500 +/- 2700 and 50,500 +/- 900 in human and rat
      preparations, respectively. VIP receptors were functional, since VIP stimulated
      adenylyl cyclase activity in a dose dependent manner with similar efficacy but
      different potency in human (ED50 = 1.2 nM) and rat (ED50 = 5.8 nM) liver
      membranes.

PMID- 8148399
TI  - Cyclosporin A antagonizes phenylephrine, oxytocin and angiotensin effects on
      glucose metabolism in rat thymus lymphocytes.
AB  - Effects of phenylephrine, oxytocin and angiotensin on fructose 2,6-bisphosphate
      (Fru 2,6-P2) content and glycolytic parameters were studied in incubated thymus
      lymphocytes. These hormones modified Fru 2,6-P2 content dependent upon the
      energetic status of the cells. In non-preincubated thymus lymphocytes (with
      relatively high levels of glycogen and ATP), phenylephrine, oxytocin and
      angiotensin depressed Fru 2,6-P2 content in a dose-dependent manner. The opposite
      was found when the cells were preincubated for 2 h without substrates (low levels
      of ATP and glycogen). Changes in lactate release were less evident, but
      significant. Phenylephrine did not modify the maximal activities of
      phosphofructokinase (PFK)-1 or PFK-2. However, both submaximal PFK-1 and PFK-2
      activities were inhibited by phenylephrine, and the response to exogenous Fru 2,6
      P2 on PFK-1 was also altered. The activities of Fru 1,6-P2 and pyruvate kinase
      were not modified by phenylephrine or A23187 treatment. Simultaneous presence of
      Cyclosporin A (CsA), an immunosuppressive drug, antagonizes the alpha-adrenergic
      effect on Fru 2,6-P2 content. CsA alone did not alter basal levels of ATP, hexose
      phosphate or Fru 2,6-P2, and its opposing effect to alpha-agonist was dose
      dependent. CsA cannot change the positive action of PMA or the negative action of
      A23187 on Fru 2,6-P2 content. The present data suggest that CsA acts prior to
      calcium liberation and protein kinase C activation. Different possible molecular
      models are discussed.

PMID- 8148400
TI  - Bombesin stimulates transplasma-membrane electron transport by Swiss 3T3 cells.
AB  - Bombesin, a mitogenic neuropeptide, stimulates transplasmalemma reduction of
      diferric transferrin or ferricyanide by Swiss 3T3 cells. The stimulation of
      diferric transferrin reduction occurs in the range of bombesin concentrations
      that stimulate proliferation of Swiss 3T3 cells. Diferric transferrin reduction
      by the 3T3 cells is accompanied by increased proton release from the cells and
      bombesin increases the differic transferrin-stimulated proton release twofold.
      Insulin increases the diferric transferrin reductase response and increases
      growth stimulation with bombesin. The effect of bombesin on the transmembrane
      electron transport is a new aspect of its effect on the plasma membrane in
      addition to increase in phosphatidylinositol turnover and protein kinase c
      activation. The electron transport can provide an independent mechanism of
      activation of the Na+/H+ exchange or it can change the redox state of pyridine
      nucleotide in the cytoplasm.

PMID- 8148401
TI  - Vascular endothelial growth factor/vascular permeability factor is detectable in
      the sera of tumor-bearing mice and cancer patients.
AB  - We developed an enzyme-linked immunosorbent assay (ELISA) for vascular
      endothelial growth factor/vascular permeability factor (VEGF/VPF). The assay
      revealed that VEGF/VPF levels in the sera of mice were significantly increased
      from undetectable level by s.c. transplantation with a solid tumor. We also
      measured VEGF/VPF levels in serum specimens obtained from cancer patients with
      several types of cancers. VEGF/VPF levels in the sera from cancer patients were
      significantly higher than those in the sera from the individuals with no sign of
      cancer.

PMID- 8148402
TI  - 252Cf-plasma desorption mass spectrometry. II--A perspective of new directions.
AB  - The 252Cf-PDMS method is a 'mature' technique, having survived 20 years of
      research, development and application. Recent advances in the application of the
      method have led to the use of the technique in clinical quantitation studies, the
      development of a microscopic method for measuring chemical homogeneity, in situ
      applications where serial modifications can be made and studied in a sequential
      fashion and the utilization of the primary fragmentation patterns to correlate
      with primary structure. Future directions in research, development and
      application will focus more attention on the chemistry of the 252Cf-PDMS process
      and the understanding and control of gas-phase reactions that occur in the
      ejection plume. Predictions are that the application of the in situ modification
      technique could lead to a new approach to pharmacokinetic studies as well as cell
      surface interactions where 252Cf-PDMS is effectively used to expand the
      capabilities of in vitro studies of biological processes.

PMID- 8148403
TI  - Short-column gas chromatography/tandem mass spectrometry for the detection of
      underivatized anabolic steroids in urine.
AB  - Short-column (3.5 m) gas chromatography (GC)/tandem mass spectrometry (MS/MS) has
      been investigated for the detection of structurally related, underivatized
      anabolic steroids in urine. The approach described here demonstrates the ability
      to rapidly and qualitatively detect underivatized anabolic steroids in spiked
      urine matrices. In this approach, underivatized steroids are determined using a
      short-column GC separation, ionized by positive ion chemical ionization, and
      detected by selected reaction monitoring MS/MS. This approach permits positive
      identification of underivatized anabolic steroids based on retention time and the
      production of characteristic product ions. Preliminary detection limits studies
      in spiked urine samples showed quantitative results between 2 and 40 ng steroid
      per milliliter of uterine. The potential advantages of this approach compared to
      present screening methods based on conventional (30 m) GC/MS are its rapidity and
      selectivity. Reliable qualitative identification can be performed with a short
      column GC/MS/MS analysis of less than 6 min with a reduction in sample
      preparation time due to the elimination of the derivatization step.

PMID- 8148404
TI  - Analysis of phenoxazine chemosensitizers: an electron ionization and keV-ion beam
      bombardment mass spectrometry study.
AB  - The mass spectral behavior of a set of eight 2- and 10-disubstituted phenoxazines
      putatively possessing anticancer drug enhancer properties was investigated. Both
      electron ionization (EI) and keV-ion beam bombardment (liquid secondary ion mass
      spectrometry, LSIMS) were used. As expected, EI led to extensive fragmentation to
      produce structurally characteristics ions. Except in one example, the molecular
      ions were reasonably abundant. Two different liquid matrices--sulfolane and 3
      nitrobenzyl alcohol--were used to obtain LSIMS data. The use of the latter
      produced more stable molecular ions. Ion beam bombardment also produced several
      structure-specific fragments. A unique feature of the LSI spectra obtained using
      either of the above matrices is production of both M+. and [M + H]+ ions, with
      the former being more abundant in most cases. Adduct formation with the liquid
      matrices was also observed for many compounds.

PMID- 8148405
TI  - Identification of clozapine N(+)-glucuronide in the urine of patients treated
      with clozapine using electrospray mass spectrometry.
AB  - Clozapine N(+)-glucuronide was detected in the urine of five patients chronically
      treated with clozapine. Identification was made on the basis that the material
      isolated from urine had the same high-performance liquid chromatographic
      retention time and positive electrospray mass spectra as that of an authentic
      reference standard of clozapine N(+)-glucuronide. These results indicate that
      electrospray mass spectrometry is a valuable technique in the analysis of low
      molecular-weight biologically derived N(+)-glucuronide metabolites.

PMID- 8148406
TI  - The determination of cyclophosphamide and its metabolites in blood plasma as
      stable trifluoroacetyl derivatives by electron capture chemical ionization gas
      chromatography/mass spectrometry.
AB  - A method is described for the determination of the antitumour drug
      cyclophosphamide and six stable metabolites in plasma of cancer patients, namely
      dechloroethyl-cyclophosphamide, 4-keto-cyclophosphamide, carboxy-phosphamide,
      alcophosphamide, nor-nitrogen mustard and the N-chloroethyl-1,3-oxazolidine-2
      one, as methyl and/or trifluoroacetyl derivatives by single ion monitoring gas
      chromatography/mass spectrometry, mostly in the electron capture chemical
      ionization mode. The isolation of most metabolites was performed by solid-phase C
      18 extraction in weakly acidic medium. The phosphoramide mustard isolated under
      these conditions decomposes readily to the nor-nitrogen mustard during
      derivatization. The original nor-nitrogen mustard and the chloroethyl-1,3
      oxazolidine-2-one were isolated by liquid extraction with ethyl acetate in
      alkaline medium. Recoveries of 75-99% were measured using spiked blank plasma
      samples. Quantitation of metabolites in patient plasma samples was performed
      using two sets of calibration curves for the concentration ranges of 1-100 ng and
      0.1-10 micrograms of metabolite per millilitre of original plasma.

PMID- 8148407
TI  - beta-Lactamase ragged ends detected by electrospray mass spectrometry correlates
      poorly with multiple banding on isoelectric focusing.
AB  - Purified preparations of TEM-2, P99, Bacillus cereus I and B. cereus II beta
      lactamases were examined by electrospray (ES) mass spectrometry. The ES mass
      spectra of the B. cereus enzymes revealed the presence of four to five components
      of different mass, corresponding to the loss of different numbers of N-terminal
      amino acids (ragged ends). The ES mass spectra of both TEM-2 and P99 consisted of
      a single component with no evidence of ragged ends. All four beta-lactamase
      preparations were visualized on isoelectric focusing (IEF) gels stained with
      nitrocefin to investigate a possible correlation between IEF patterns and ragged
      ends. Multiple banding patterns were seen with each beta-lactamase preparation.
      Although these may correlate with the presence of ragged ends in the two B.
      cereus preparations, the satellite bands seen with P99 and TEM-2 were not
      associated with differences detected by ES mass spectrometry. In this study we
      have shown for the first time that beta-lactamase satellite bands seen on IEF are
      not always associated with ragged ends. Furthermore, we have illustrated the use
      of ES mass spectrometry to characterize the extent of ragged end formation in
      protein samples. This is of particular significance if the sample is required for
      detailed biochemical or crystallography experiments.

PMID- 8148408
TI  - Determination of prostaglandin E1 and its main plasma metabolites 15-keto
      prostaglandin E0 and prostaglandin E0 by gas chromatography/negative ion chemical
      ionization triple-stage quadrupole mass spectrometry.
AB  - Prostaglandin E1 (PGE1), 15-keto-PGE0 and PGE0 in plasma were determined in an
      isotope dilution assay by gas chromatography/triple-stage quadrupole mass
      spectrometry. After addition of deuterated internal standards, the prostaglandins
      were extracted by a solid-phase cartridge and derivatized to the
      pentafluorobenzyl ester methoxime. The samples were purified by thin-layer
      chromatography, converted to the trimethylsilyl ethers and quantified by gas
      chromatography/triple-stage quadrupole mass spectrometry. The parent ions in the
      negative ion chemical ionization mode were [M-pentafluorobenzyl]- ([P]-), the
      daughter ions used for quantification were [P-(CH3)3SiOH]- (PGE0 and 15-keto
      PGE0) and [P-2(CH3)3SiOH]- (PGE1), respectively. Plasma concentrations in healthy
      subjects were at about 1-3 pg ml-1 for PGE1 and PGE0 and 2-15 pg ml-1 for 15-keto
      PGE0. After infusion of 60 micrograms PGE1 in 2 h, the concentrations in plasma
      were 3-10 pg ml-1 for PGE1, 8-17 pg ml-1 for PGE0 and 115-205 pg ml-1 for 15-keto
      PGE0.

PMID- 8148409
TI  - Simulation of visual cortex development under lid-suture conditions: enhancement
      of response specificity by a reverse-Hebb rule in the absence of spatially
      patterned input.
AB  - In this report, I show that a reverse-Hebb synaptic modification rule leads to
      the enhancement of response specificity of simulated visual cortex neurons in the
      absence of spatial patterning of the afferent activity. Although it is clear that
      receptive fields in the visual cortex can be modified by experience, many studies
      have shown a substantial increase of response specificity in cats deprived of
      pattern vision by lid suture, leading some to conclude that receptive field
      properties are essentially hard-wired. The hard-wired vs. experience-dependent
      controversy can be resolved by assuming that while Hebb-type plasticity is
      responsible for developmental synaptic changes, the organization of presynaptic
      activity which exists under conditions of visual deprivation is sufficient to
      drive the neurons towards greater specificity (Linsker 1986a-c; Miller 1989,
      1992; Miller et al. 1989). As a reverse-Hebb rule enhances response specificity
      by balancing the push-pull system of ON- and OFF-center afferents, the sufficient
      condition is that the activity of ON- and OFF-center retinal ganglion cells be
      negatively correlated, a condition which will be met by diffuse illumination as
      seen through sutured eyelids. Unlike the models of Linsker and Miller and
      colleagues, which are based on a standard-Hebb rule, the model presented here
      does not require the presence of a "Mexican hat" spatial patterning of the
      afferent correlations, which has not been observed experimentally.

PMID- 8148410
TI  - Simulations of a ventrolateral medullary neural network for respiratory
      rhythmogenesis inferred from spike train cross-correlation.
AB  - Connections among ventrolateral medullary respiratory neurons inferred from spike
      train analysis were incorporated into a model and simulated with the program
      SYSTM11 (MacGregor 1987). Inspiratory (I) and expiratory (E) neurons with
      augmenting (AUG) and decrementing (DEC) discharge patterns and rostral I-E/I
      neurons exhibited varying degrees of adaptation, but no endogenous bursting
      properties. Simulation parameters were adjusted so that respiratory phase
      durations, neuronal discharge patterns, and short-time scale correlations were
      similar to corresponding measurements from anesthetized, vagotomized, adult cats.
      Rhythmogenesis persisted when the strength of each set of connections was
      increased 100% over a smaller effective value. Changes in phase durations and
      discharge patterns caused by manipulation of connection strengths or population
      activity led to several predictions. (a) Excitation of the I-E/I population
      prolongs the inspiratory phase. (b) Rhythmic activity can be reestablished in the
      absence of I-E/I activity by unpatterned excitation of I-DEC and I-AUG neurons.
      (c) An increase in I-DEC neuron activity can cause an apneustic respiratory
      pattern. (d) A decrease in I-DEC neuron activity increases the slope of the
      inspiratory ramp and shortens inspiration. (e) Excitation of the E-DEC population
      prolongs the expiratory phase or produces apnea; inhibition of E-DEC neurons
      reduces expiratory time. (f) Excitation of E-AUG cells causes I-AUG neurons to
      exhibit a step rather than a ramp increase in firing rate at the onset of their
      active phase. The results suggest mechanisms by which the duration of each phase
      of breathing and neuronal discharge patterns may be regulated.

PMID- 8148411
TI  - Chaos in percepts?
AB  - Multistability in perceptual tasks has suggested that the mechanisms underlying
      our percepts might be modeled as nonlinear, deterministic systems that exhibit
      chaotic behavior. We present evidence supporting this view, obtaining an estimate
      of 3.5 for the dimensionality of such a system. A surprising result is that this
      estimate applies for a rather diverse range of perceptual tasks.

PMID- 8148412
TI  - Simulations of the alpha motoneuron pool electromyogram reflex at different
      preactivation levels in man.
AB  - The alpha motoneuron pool and the surface electromyogram (EMG) of the human
      soleus muscle are modelled, respectively, by an alpha motoneuron pool model
      generating the firing patterns in the motor units of the muscle and by a muscle
      model using these discharge patterns to simulate the surface EMG. In the alpha
      motoneuron pool model, we use a population of motoneurons in which cellular
      properties like cell size and membrane conductance are distributed according to
      experimentally observed data. By calculating the contribution from each motor
      unit, the muscle model predicts the EMG. Wave forms of the motor unit action
      potentials in the surface EMG are obtained from experimental data. Using the
      model, we are able to give a quantitative prediction of the motoneuron pool
      activity and the reflex EMG output at different preactivation levels. The
      simulated data are consistent with experimentally obtained results in healthy
      humans. During static isometric muscle preactivations, the simulations show that
      the reflex strength is highly dependent on the intrinsic threshold properties of
      the alpha motoneuron pool.

PMID- 8148413
TI  - Reduced-system analysis of the effects of serotonin on a molluscan burster
      neuron.
AB  - The mathematical model described in Bertram (1993) is used to carry out a
      detailed examination of the manner in which the neurotransmitter serotonin
      modifies the voltage waveform generated endogenously by burster neuron R15 of
      Aplysia. This analysis makes use of a reduced system of equations, taking
      advantage of the slow rate of change of a pair of system variables relative to
      the others. Such analysis also yields information concerning the sensitivity of
      the neuron to brief+ synaptic perturbations.

PMID- 8148414
TI  - Phase-entrainment dynamics of visually coupled rhythmic movements.
AB  - Do interlimb rhythmic coordinations between individuals exhibit the same
      relations among the same observable quantities as interlimb rhythmic coordination
      within an individual? The 1:1 frequency locking between the limbs of two people
      was investigated using a paradigm in which each person oscillated a hand-held
      pendulum, achieving and maintaining the mutual entrainment through vision. The
      intended coordination was antiphase, phi = pi, and the difference between the
      uncoupled eigen-frequencies, delta omega, was manipulated through differences in
      the lengths of the two pendulums. The mean phase relation and its variance for
      visually coupled coordinations differing in delta omega were predicted by an
      order parameter equation developed by Haken et al. (1985) and Schoner et al.
      (1986) for the relative phase of correlated movements of limb segments.
      Specifically, the experiment revealed that: (1) the deviation of phi from pi
      increased with increasing deviation of delta omega from 0; and (2) fluctuations
      in phi increased with increasing deviation of delta omega from 0. With deviations
      of delta omega from 0, new peaks were added at higher harmonics in phi's power
      spectrum. These results were in agreement with previous research on the stable
      states of interlimb coordination within a person, mediated by mechanoreceptive
      rather than photoreceptive mechanisms. Additionally, they were in agreement with
      previous research on phase transitions in interlimb coordination which have been
      shown to conform to the same order parameter dynamics whether the coupling be
      mechanoreceptively or photoreceptively based. It was suggested that phase
      entrainment in biological movement systems may abide by dynamical principles that
      are indifferent to the details of the coupling.

PMID- 8148415
TI  - Coincidence of familial platelet glycoprotein Ib/IX deficiency (Bernard-Soulier
      syndrome), idiopathic autoantibody against platelet glycoprotein Ib/IX, familial
      appearance of antiphospholipid antibodies, and familial factor XII deficiency.
AB  - The case of an 8-year-old boy with apparently homozygous Bernard-Soulier syndrome
      (platelet GP Ib/IX complex deficiency) and a transient idiopathic autoantibody
      against GP Ib/IX is described. He had been diagnosed with chronic autoimmune
      thrombocytopenia (due to the detection of antiplatelet autoantibodies) before
      Bernard-Soulier syndrome was proven. Both parents and his brother displayed
      intermediate deficiency of GP Ib/IX, thus indicating a heterozygote state for
      Bernard-Soulier syndrome. Alloimmunization as an explanation for the appearance
      of GP Ib/IX antiplatelet antibodies in the propositus can be excluded. A so
      called pseudo Bernard-Soulier syndrome due to selective antibodies was also
      excluded. Flow cytometric analysis revealed residual expression of 2% GP Ib and
      13% GP IX on the propositus' platelets. It seems that the propositus showed an
      idiopathic autoantibody against a platelet glycoprotein in which he is
      genetically deficient (but which is not completely lacking). Thus, in patients
      with untypical behavior upon therapy of "autoimmune thrombocytopenia", other
      differential diagnoses should also be considered even if antiplatelet antibodies
      are detected. In addition, all family members displayed elevated concentrations
      of antiphospholipid antibodies. These findings raise the question of a genetic
      predisposition for the development of autoantibodies. Moreover, an F. XII
      deficiency was found in all family members except the mother.

PMID- 8148416
TI  - Chronic neutrophilic leukemia. A study of four cases.
AB  - Chronic neutrophilic leukemia (CNL) is a very rare entity, which has to be
      included among the chronic myeloid leukemias. Once an underlying cause of
      neutrophilia is excluded, the diagnosis of CNL is based on exclusion of chronic
      granulocytic and other types of chronic myeloid leukemias. The classification
      proposed by Sheperd et al. has proven to be helpful, but it must be completed by
      cytogenetic analysis and the search for bcr rearrangement by molecular biology
      methods, in order to confirm the absence of Philadelphia chromosome and of bcr
      abl hybrid gene. We report here four cases of CNL, with confirmed absence of bcr
      rearrangement in two cases. Two patients died, 12 and 8 years after diagnosis,
      the second one following transformation into myelofibrosis with myeloid
      metaplasia. The other two died of acute myelogenous leukemia, the first one, 25
      years after diagnosis of CNL, following a 3-year phase of acceleration. The last
      patient presented combined features of CNL and refractory anemia with excess of
      blasts, and was characterized by both progressive leukocytosis and severe
      thrombocytopenia; acute transformation into acute myelogenous leukemia occurred 6
      months after diagnosis and death 1 month later. Among the 30 cases reported so
      far, plus the four presented here, combined myelodysplastic features were
      observed in five cases and transformation into acute myelogenous leukemia in six.
      Chronic neutrophilic leukemias should be reported regularity, in view of the
      uncertain and low frequency of this hematological disease.

PMID- 8148417
TI  - The impact of EBV, proliferation rate, and Bcl-2 expression in Hodgkin's disease
      in childhood.
AB  - The role of Epstein-Barr virus (EBV) in the pathogenesis of Hodgkin's disease
      (HD) has not yet been clarified. Using RNA in situ hybridization (ISH) and
      immunohistochemistry (IHC), the occurrence of small Epstein-Barr virus encoded
      RNA (EBER) and latent membrane protein-1 (LMP-1) was studied in 22 tissue samples
      from 21 patients between 4 and 17 years of age with Hodgkin's disease. EBER was
      detected in eight of 21 patients (38%) in Hodgkin and Reed-Sternberg cells and
      reactive lymphocytes irrespective of initial clinical stage and histological
      subtype, whereas LMP-1, positive in ten of 21 patients (48%), was restricted to
      neoplastic cells. All cases positive for EBER expressed LMP-1 as well.
      Additionally, oncoprotein Bcl-2 was identified in nine of 21 patients (43%),
      indicating, besides immortalization of HD cells by EBV, a further growth
      advantage due to apoptosis prevention by overexpression of this protein.
      Proliferation-associated antigens Ki-S1 and Ki-S5 were highly expressed in
      Hodgkin and Reed-Sternberg cells. CD 30 antigen was found in most cases, using
      two different antibodies (90% and 80%). The presence of this protein, which
      belongs to the family of nerve growth factor receptor (NGFR), is related to high
      expression of Ki-67 protein, detected by Ki-S5. CD 20 antigen was detectable in
      only three of 21 patients (14%). If we compare results of ISH and IHC with
      clinical data, the occurrence of EBV genome in children with HD seems to have no
      adverse effect on the final outcome of these patients.

PMID- 8148418
TI  - Defective burst-promoting activity of T lymphocytes from anemic and nonanemic
      elderly people.
AB  - Erythroid stem cell proliferation is regulated by lymphokines and erythropoietin.
      The helper subset of T lymphocytes is known to produce the erythroid growth
      factor IL-3 or burst-promoting activity (BPA), while the suppressor subset seems
      to inhibit the erythroid growth. Leukocyte-conditioned media derived from white
      cells of nonanemic elderly were reported to provide defective support to the
      erythropoiesis. In two groups of elderly, nonanemic and anemic, we studied the
      ability of T lymphocytes to stimulate the BFU-E growth and the in vitro effect of
      cimetidine, as a drug that inhibits the suppressor T lymphocytes. Culture data
      were then compared with the peripheral blood lymphocyte picture. The study shows
      that defective mononuclear cell support to the BFU-E growth, namely due to
      reduced absolute number of the T4 subset of T lymphocytes, can be observed in
      both anemic and nonanemic elderly. It is suggested that isolated defective BPA
      production is not always sufficient to induce anemia. In most cases, anemia of
      unexplained origin in senescence would be due to the concomitance of both BFU-E
      impairment and defective BPA production. The simultaneous evaluation of BFU-E
      growth, lymphokine production, and the T-lymphocyte blood picture offers the best
      way to investigate the erythropoiesis of the elderly.

PMID- 8148419
TI  - Hb Cemenelum [alpha 92 (FG4) Arg-->Trp]: a hemoglobin variant of the alpha 1/beta
      2 interface that displays a moderate increase in oxygen affinity.
AB  - Hb Cemenelum [alpha 92 (FG4) Arg-->Trp] carries a structural modification at the
      same position as Hb Chesapeake, a very high oxygen affinity variant. Hb Cemenelum
      was found in a French diabetic patient with no abnormal hematological features.
      The purified abnormal hemoglobin, like Hb J Cape Town, another variant of
      position alpha 92(FG4), displayed only a 1.5- to 2-fold increased oxygen affinity
      and a reduced cooperativity. This hemoglobin demonstrates that, even for some key
      residues of the alpha 1/beta 2 interface, the degree at which the functional
      properties are altered depends upon the specific residue occupying this position.

PMID- 8148420
TI  - Possible effect of medroxyprogesterone acetate (MPA) in lymphoid blast crisis of
      chronic myelogenous leukemia.
AB  - A patient with a lymphoid blast crisis of a chronic myelogenous leukemia (CML)
      was treated with vindesine, vincristine and prednisone. Blasts disappeared from
      the peripheral blood but persisted at a level of 60% in the bone marrow. After 5
      weeks of continuous therapy, the patient became thrombopenic, and 2 weeks later
      blasts rose to 31%. After 7 weeks, 1 g MPA was given daily p.o. and weekly
      vincristine treatment was resumed. Blasts disappeared again from the peripheral
      blood, thrombocytes rose to a maximum of 274 g/l, and a remission with less than
      5% blasts was demonstrated in the bone marrow. In another relapse after
      withdrawal of MPA, estrogen and progesterone receptors (PR) were found in the
      leukemic cells. Thus, a remission was seen during treatment with vincristine,
      prednisone, and MPA after a deterioration with vincristine and prednisone alone
      in a PR-positive leukemia, and an effect of MPA in this lymphoid blast crisis of
      a CML has to be discussed.

PMID- 8148421
TI  - Acute parotitis during induction therapy including L-asparaginase in acute
      lymphoblastic leukemia.
AB  - In a patient affected by acute lymphoblastic leukemia (ALL) and subjected to
      therapy with Erwinia L-asparaginase, acute parotitis was observed.
      Microbiological studies excluded any infectious etiology. Regression of parotitis
      was spontaneous. This complication has not been previously reported and could be
      due to the same mechanism of pancreatic injury. The occurrence of acute parotitis
      needs to be promptly recognized in order to avoid the continuation of L
      asparaginase.

PMID- 8148422
TI  - Trisomy 21 as the sole clonal aberration in a patient with acute myelomonocytic
      leukemia with abnormal bone marrow eosinophils and extramedullary involvement.
AB  - We describe a 30-year-old acute myelomonocytic leukemia patient with abnormal
      bone marrow eosinophils (AML FAB subtype M4Eo) with extensive extramedullary
      involvement and, in the abscence of an aberration involving chromosome 16, clonal
      trisomy 21 in the leukemic blast cells.

PMID- 8148423
TI  - Granulocytic sarcoma of the prostate as the first manifestation of a late relapse
      of acute myelogenous leukemia.
AB  - We describe a 68-year-old patient who developed granulocytic sarcoma of the
      prostate 9 years after complete remission following successful treatment of acute
      myelogenous leukemia (FAB, M2). PCR analysis of bone marrow samples in first
      remission and at the time of relapse detected an AML1/ETO rearrangement typical
      for AMLs with t (8;21). The CD56 antigen was not expressed on the leukemic cells.
      Systemic chemotherapy led to a short-lasting regression of the tumor, but the
      patient subsequently developed overt bone marrow relapse and died during
      chemotherapy. While granulocytic sarcoma as a primary manifestation of AML is
      well known, as the first manifestation of relapse it appears to be very uncommon.

PMID- 8148424
TI  - Implantology for the future.

PMID- 8148425
TI  - Restoring the anterior maxillary arch with an implant supported fixed bridge.

PMID- 8148426
TI  - Peri-implantitis.

PMID- 8148427
TI  - A new angle on restoring anterior teeth with root-form implants: clinical report.
AB  - Root-form implants may be indicated for the replacement of missing anterior
      teeth. Occasionally fixtures are placed in a position inconsistent with proper
      tooth alignment. The new PreAngled Abutment (Dentsply/Implant Division, Encino,
      CA) addresses this problem and was used to successfully restore missing tooth
      numbers 7 and 8 for a patient that had two malpositioned implants.

PMID- 8148428
TI  - Single tooth replacement with a combined post-and-crown implant prosthesis: a
      case report.
AB  - A patient desiring restoration of an individual second molar requested an
      osseointegrated implant. However, this patient lacked sufficient vertical space
      to accommodate a cemented crown, and did not want to compromise the adjacent
      dentition. A combination post-and-crown prosthesis effectively restored function
      and clinically acceptable aesthetics for this patient. The techniques for
      fabrication and rationale for this type of prosthesis are discussed.

PMID- 8148429
TI  - Introduction to plasma glow discharge treatment of dental implants.
AB  - As more practitioners are using implants in their practice, more questions have
      arisen regarding the use of these devices. One very important factor is the type
      of bone-implant interface obtained. The more inert and stable over time the metal
      is, the more we can control the overall success of the implant. Plasma glow
      discharge treatment is an ideal technique to increase the wettability of the
      metal and to insure a sound bone-implant interface. This article is an
      introduction to the use of plasma glow discharge treatment on dental implants.

PMID- 8148430
TI  - Replacing four mandibular incisors with an implant supported prosthesis.

PMID- 8148431
TI  - Diacetyl for blocking the histochemical reaction for arginine.
AB  - Two different histochemical methods for blocking the guanidinium group of
      arginine in formalin fixed, paraffin embedded material are reported here. One
      procedure uses diacetyl with short incubation times and high pH, the other uses
      the trimer of the diacetyl reagent and requires longer incubation times but
      moderate pH. The diacetyl reagent is recommended despite its high pH because the
      preparation of the diacetyl trimer is laborious and time-consuming.

PMID- 8148432
TI  - Detection of Staphylococci in mouse phagocytic cells by in situ hybridization
      using biotinylated DNA probes.
AB  - In situ hybridization was used to detect intracellular Staphylococcus aureus and
      S. epidermidis in mouse phagocytic cells after experimental infection of C3H mice
      with Staphylococci via abdominal or intravenous injection. Isolated ascites or
      whole blood were tested by the phagocyte smear technique, using bacteriolytic
      enzymes to preserve phagocytic cell morphology. The exposed bacterial DNA was
      visualized as intracellular hybridized signals by use of biotinylated DNA probes
      and by immunocytochemistry using streptavidin-alkaline phosphatase conjugates as
      detector molecules. These DNA probes, prepared from randomly cloned genomic DNA
      fragments of S. aureus and S. epidermidis, were strain-specific and did not cross
      hybridize either in situ or on dot-blot hybridization. This technique of in situ
      hybridization with phagocyte smears is useful for detection and diagnosis of
      intracellular bacteria regardless of viability.

PMID- 8148433
TI  - A variant of a slam freezing device for electron microscopy.
AB  - A home-made slam freezing device is presented that allows reproducible results in
      freezing various unfixed tissues. The heart of the device is an aluminum socket,
      which harbors a plunger that is set in motion by a spring. At the end of the
      plunger there is an electromagnet which holds the sample on a sheet metal
      planchette. During stop freezing the electrical contacts are interrupted and the
      plunger can be withdrawn leaving the specimen on the cooled copper block. This
      guarantees freezing of not only solid tissues, but also cell suspensions, such as
      blood or bone marrow.

PMID- 8148434
TI  - Removal of biological stains from aqueous solution using a flow-through
      decontamination procedure.
AB  - Chromatography columns filled with Amberlite XAD-16 were used to decontaminate,
      using a continuous flow-through procedure, aqueous solutions of the following
      biological stains: acridine orange, alcian blue 8GX, alizarin red S, azure A,
      azure B, brilliant blue G, brilliant blue R, Congo red, cresyl violet acetate,
      crystal violet, eosin B, eosin Y, erythrosin B, ethidium bromide, Giemsa stain,
      Janus green B, methylene blue, neutral red, nigrosin, orcein, propidium iodide,
      rose Bengal, safranine O, toluidine blue O, and trypan blue. Adsorption was most
      efficient for stains of lower molecular weight (< 600). Adsorption of stain
      increased as the flow rate decreased; column diameter had little effect on
      adsorption. Adsorption of stain was greatest when finely ground resin was used,
      but if the resin particles were too small, column clogging occurred. Limited
      grinding of the resin gave increased adsorption while retaining good flow
      characteristics. Amberlite XAD-16 saturated with methylene blue was regenerated
      to its initial adsorption capacity by passing methanol through the column. The
      technique described provides an economical, rapid means of removing stains from
      aqueous solution.

PMID- 8148435
TI  - A comparison of cognitive behavioral treatment for chronic fatigue syndrome and
      primary depression.
AB  - To evaluate the effect of cognitive behavioral intervention on chronic fatigue
      syndrome (CFS), we studied three patient groups: a CFS-treatment group (n = 22),
      a primary depression-treatment group (n = 20), and a no-treatment control group
      of subjects with CFS (n = 22). For the CFS-treatment group, a trend toward
      reduced depression-symptom scores was noted, but there were no significant
      changes in stress-related symptoms or fatigue severity. For the most depressed
      treated subjects with CFS, significant score reductions were observed in measures
      of depression, stress, fatigue severity, and fatigue-related thinking. In the
      depression group, significant reductions in depression, stress, and fatigue
      severity scores were found. No significant changes in any measure were observed
      in the CFS control group. A new fatigue-related cognitions scale, developed to
      assess cognitive and emotional reactions to fatigue, showed a significant
      reduction in such reactions in the CFS-treatment group, a finding suggesting that
      depression in this group was mediated by maladaptive thinking. The results
      suggest that a subset of CFS patients with cognition-related depressive
      symptomatology may respond to short-term behavioral intervention.

PMID- 8148436
TI  - A comparison of case definitions of chronic fatigue syndrome.
AB  - We compared three case definitions of chronic fatigue syndrome (CFS) applied to
      patients followed in CFS clinics at two institutions. All patients had
      debilitating fatigue without apparent etiology; patients with medical conditions
      associated with chronic fatigue and with major psychiatric disorders were
      stratified and presented separately. Patients were classified according to
      whether they met case definitions developed by a Centers for Disease Control and
      Prevention (CDC) Working Group, a British group, or an Australian group. When
      findings for 805 patients followed at the two clinics were combined, 61% met the
      CDC criteria, 55% met the British criteria, and 56% met the Australian criteria;
      these proportions were relatively similar at both sites. In addition, similar
      laboratory abnormalities were found for all case groups and for fatigued patients
      who met none of the three case definitions. These data suggest that more
      inclusive case definitions may be superior.

PMID- 8148437
TI  - Viral studies of chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) has many characteristics suggesting persistent
      fatigue following a viral illness. At least nine different RNA and DNA viruses
      have been considered to be associated with this disease, but none of these
      viruses has been found to be the etiologic agent. Immunologic studies have
      demonstrated activated CD8+ cells and reduced function of natural killer cells
      suggesting a host response to an infection that has led to persistent immune
      disorders. Some of the symptoms of CFS may be due to cytokines produced by this
      hyperactive immune response to a virus that is still present in the host or that
      has been eliminate but leaves abnormal immunologic sequelae. These possibilities
      offer directions for future studies of CFS and therapeutic approaches to this
      condition.

PMID- 8148438
TI  - Lack of evidence for infection with known human and animal retroviruses in
      patients with chronic fatigue syndrome.
AB  - We investigated 21 patients with chronic fatigue syndrome who were identified
      through the surveillance system of the Centers for Disease Control and Prevention
      (CDC) in Atlanta for the presence of several human and animal retroviruses. In
      addition, we evaluated 21 CDC employee controls matched with the patients for age
      (+/- 5 years), gender, and race. The viruses tested included human T-lymphotropic
      viruses types I and II; human spuma retrovirus; simian T-lymphotropic virus type
      I; simian retroviruses types 1, 2, and 3; bovine leukemia virus; feline leukemia
      virus; and gibbon ape leukemia virus. Samples of peripheral blood lymphocytes and
      leukocytes from patients and controls were analyzed in a blinded fashion for
      retroviral sequences; polymerase chain reaction (PCR) amplification assays and
      Southern blot hybridization to 32P-labeled internal oligoprobes were used. All
      PCR assays were optimized for maximal sensitivity on respective infected cell
      lines or plasmids, and sensitivity controls were included in each experiment. All
      samples from patients and controls were negative for the tested retroviral
      sequences. Our data indicate that none of these retroviruses plays an etiologic
      role or is a cofactor in the chronic fatigue syndrome illnesses of our study
      population.

PMID- 8148439
TI  - Studies on enterovirus in patients with chronic fatigue syndrome.
AB  - A large study on 121 patients with the chronic fatigue syndrome (CFS) that
      examined muscle biopsy samples for enterovirus by means of polymerase chain
      reaction analysis was carried out. The results were compared with those obtained
      from 101 muscle biopsy specimens from patients with a variety of other
      neuromuscular disorders (OND), including neurogenic atrophies, dystrophies, and
      mitochondrial, metabolic, and endocrine myopathies. Thirty-two (26.4%) of the
      biopsy specimens from the group of patients with CFS were positive, compared with
      20 (19.8%) from the group of patients with OND, a difference that was not
      significant. This finding is in contrast to those of our previous smaller study
      in which significantly more patients with CFS than control subjects (53% [32 of
      60] vs. 15% [6 of 41]) had enterovirus RNA sequences in their muscle. It was
      concluded that it is unlikely that persistent enterovirus infection plays a
      pathogenetic role in CFS, although an effect in initiating the disease process
      cannot be excluded.

PMID- 8148440
TI  - Viral studies of chronic fatigue syndrome.

PMID- 8148441
TI  - Immunologic abnormalities associated with chronic fatigue syndrome.
AB  - Several aspects of cellular immunity in patients with clinically defined chronic
      fatigue syndrome (CFS) were evaluated and compared with those in healthy
      individuals. Flow cytometric analyses revealed normal expression of total T
      (CD3+), B (CD19+), and NK (natural killer) (CD16+, CD56+) markers on the surface
      of peripheral blood mononuclear cells (PMC) from patients with CFS. However,
      compared with those of healthy individuals, patients' CD8+ T cells expressed
      reduced levels of CD11b and expressed the activation markers CD38 and HLA-DR at
      elevated levels. In many of the individuals in whom expression of CD11b was
      reduced the expression of CD28 was increased. These findings indicate expansion
      of a population of activated CD8+ cytotoxic T lymphocytes. A marked decrease in
      NK cell activity was found in almost all patients with CFS, as compared with that
      in healthy individuals. No substantial abnormalities in monocyte activity or T
      cell proliferation were observed. The results of this study suggest that immune
      cell phenotype changes and NK cell dysfunction are common manifestations of CFS.

PMID- 8148442
TI  - Cytokine production and fatigue in patients with chronic fatigue syndrome and
      healthy control subjects in response to exercise.
AB  - We have studied the relationship between the cytokine production induced in vivo
      by prolonged isometric exercise and the symptom complex marked by fatigue in
      patients with chronic fatigue syndrome (CFS). Twelve male patients and 13 matched
      male control subjects undertook an isometric hand-grip exercise protocol
      utilizing dynamometers. Subjects undertook 30 minutes of exercise, for which the
      target force was set at 40% of the maximal voluntary contraction and the duty
      cycle was 50%. Prior to, during, and for 24 hours following the exercise, blood
      samples were collected and assayed for the presence of cytokines, including
      interferon-gamma and interferon-alpha, interleukin-1 beta, and tumor necrosis
      factor-alpha. At those times subjects also completed the Profile of Mood States
      (POMS) questionnaire, which served as a measure of changes in subjective fatigue.
      No significant alteration in the level of any of the cytokines in the plasma of
      patients or control subjects was detected before, during, or after exercise.
      Surprisingly, the patients' levels of fatigue, depression, and confusion, as
      measured by the POMS, decreased in response to the exercise. These data do not
      confirm the presence of an immunologic process correlating with the exacerbation
      of fatigue after exercise experienced by patients with CFS. Limitations in the
      study design and in the sensitivity of the cytokine assays may have affected our
      results.

PMID- 8148443
TI  - Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome:
      interrelations with cellular sources and patterns of soluble immune mediator
      expression.
AB  - Among a group of 70 individuals who met the criteria established by the Centers
      for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS),
      12%-28% had serum levels exceeding 95% of control values for tumor necrosis
      factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2
      receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of
      one or more of the nine soluble immune mediators tested. Nevertheless, only the
      distributions for circulating levels of TNF-alpha and TNF-beta differed
      significantly in the two populations. In patients with CFS--but not in controls-
      serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly
      with one another and (in the 10 cases analyzed) with relative amounts (as
      compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse
      transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear
      cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6
      (in order of appearance). These findings point to polycellular activation and may
      be relevant to the etiology and nosology of CFS.

PMID- 8148444
TI  - Association between HLA class II antigens and the chronic fatigue immune
      dysfunction syndrome.

PMID- 8148445
TI  - Decreased natural killer cell activity is associated with severity of chronic
      fatigue immune dysfunction syndrome.
AB  - Natural killer (NK) cell activity was measured blindly in vitro with blood
      specimens from 50 healthy individuals and 20 patients with clinically defined
      chronic fatigue immune dysfunction syndrome (CFIDS) who met the criteria
      established by the Centers for Disease Control and Prevention (Atlanta). In
      accordance with a group scoring system of 1-10 points, with 10 being the most
      severe clinical status, the patient population was stratified into three clinical
      groups: A (> 7 points), B (5-7 points), and C (< 5 points). NK cell activity was
      assessed by the number of lytic units (LU), which for the 50 healthy controls
      varied between 20 and 250 (50%, 20-50 LU; 32%, 51-100 LU; 6%, 101-130 LU; and
      12%, > 150 LU). In none of the 20 patients with CFIDS was the NK cell activity >
      100 LU. For group C, the 10 patients stratified as having the least severe
      clinical condition, the measure was 61.0 +/- 21.7 LU; for group B (more severe, n
      = 7), it was 18.3 +/- 7.3 LU; and for group A (most severe, n = 3), it was 8.0 +/
      5.3 LU. These data suggest a correlation between low levels of NK cell activity
      and severity of CFIDS, which, if it is confirmed by additional studies of larger
      groups, might be useful for subgrouping patients and monitoring therapy and/or
      the progression of CFIDS.

PMID- 8148446
TI  - Epidemic neuromyasthenia and chronic fatigue syndrome: epidemiological importance
      of a cluster definition.
AB  - Outbreaks of illness variously identified by a number of terms, including
      epidemic neuromyasthenia, myalgic encephalomyelitis, Iceland disease, and
      atypical poliomyelitis, have been reported from many countries during the past 45
      years. Since the first well-described outbreak occurring in 1934, > 60 outbreaks
      have been reported, but few of these have been described in considerable detail.
      These outbreaks are usually cited in historical reports of chronic fatigue
      syndrome (CFS) since each of these outbreaks appears to contain a number of cases
      meeting the current case definition of CFS. There has been inadequate attention
      given to the fact that epidemic neuromyasthenia and related clusters
      characterized by various complaints, including fatigue, do not have an accepted
      epidemiological or clinical definition, and only rarely have descriptions of
      these clusters included a specific case definition. When such case definitions
      have been applied, the occurrence of cases meeting the current case definition
      for CFS appears to be both variable and infrequent. This report utilizes examples
      of several well-documented outbreaks to emphasize specific aspects that should be
      considered in the investigation of future clusters.

PMID- 8148447
TI  - Primary juvenile fibromyalgia syndrome and chronic fatigue syndrome in
      adolescents.
AB  - Chronic fatigue syndrome (CFS) and primary juvenile fibromyalgia syndrome (PJFS)
      are illnesses with a similar pattern of symptoms of unknown etiology. Twenty
      seven children for whom CFS was diagnosed were evaluated for fibromyalgia by the
      presence of widespread pain and multiple tender points. Eight children (29.6%)
      fulfilled criteria for fibromyalgia. Those children who met fibromyalgia criteria
      had a statistically greater degree of subjective muscle pain, sleep disturbance,
      and neurological symptoms than did those who did not meet the fibromyalgia
      criteria. There was no statistical difference between groups in degree of
      fatigue, headache, sore throat, abdominal pain, depression, lymph node pain,
      concentration difficulty, eye pain, and joint pain. CFS in children and PJFS
      appear to be overlapping clinical entities and may be indistinguishable by
      current diagnostic criteria.

PMID- 8148448
TI  - Borrelia burgdorferi reactivity in patients with severe persistent fatigue who
      are from a region in which Lyme disease is endemic.
AB  - Borrelia burgdorferi is the pathogen that causes Lyme disease. Patients
      frequently experience fatigue and malaise that can persist after antibiotic
      treatment. This study examined serological reactivity to B. burgdorferi in
      patients with chronic fatigue who were from a region in which Lyme disease is
      endemic. Blood and CSF were collected from patients without a history of
      infection due to B. burgdorferi (n = 12) and patients with persistent fatigue
      after antibiotic treatment of Lyme disease (n = 13). Serum and CSF were examined
      by ELISA for antibodies to B. burgdorferi, and routine studies of CSF were done.
      In the first group, one patient (8%) was seropositive; no patients had detectable
      antibodies in CSF. In the second group, nine patients (69%) were seropositive or
      borderline seropositive; seven (54%) had detectable antibodies in CSF.
      Unexplained abnormalities in CSF were noted in 42% and 31% of patients in each
      group, respectively. In this study positive serologies for Lyme disease were not
      found at a higher than expected rate for patients from a region of Lyme disease
      endemicity who had idiopathic chronic fatigue. Fatigued patients did show a
      surprisingly high rate of unexplained minor CSF abnormalities suggestive of CNS
      or meningeal dysfunction.

PMID- 8148449
TI  - Chronic fatigue syndrome and a disorder resembling Sjogren's syndrome:
      preliminary report.
AB  - Chronic fatigue syndrome (CFS), as currently described in the working criteria
      proposed by the Centers for Disease Control and Prevention (Atlanta), may be
      associated with multiple, distinct, and possibly unique clinical and/or
      etiopathogenic subsets. Sjogren's syndrome (SS) is a disease of unknown etiology
      that is characterized by dryness of the mucous membranes and a variety of
      autoimmune phenomena and conditions. Subjective manifestations of SS such as
      neurocognitive dysfunction and fatigue have been stressed by some observers. We
      have detected a large number of patients with unrecognized SS-like illness in a
      clinical specializing in CFS and believe the relationship to be more than casual.
      From January 1991 through April 1992, 172 patients were evaluated for CFS; the SS
      cohort consisted of 27 females (mean age, 41.9 years). Sixteen of these patients
      had previously been found to have CFS by a physician, and 11 were self-referred.
      All patients complained of severe, dominating, chronic fatigue. Complaints of
      myalgia were prominent; 20 of 27 patients met the criteria for fibromyalgia.
      Neurocognitive complaints and/or a history of neuropsychiatric disease was
      frequent. Results of Schirmer's test were abnormal for 16 of 27, and results of
      minor salivary-gland biopsy were abnormal for 20 of 25. Antibodies to nuclear
      antigen were present in 16 of 27, but anti-Ro was present in only 1 of 21. In the
      SS group, 13 of 27 patients met eight or more CDC minor criteria for CFS, and 18
      of 27 met six or more of the criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148450
TI  - Reflections on epidemic neuromyasthenia (chronic fatigue syndrome).

PMID- 8148451
TI  - A comparative review of systemic and neurological symptomatology in 12 outbreaks
      collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and
      myalgic encephalomyelitis.
AB  - Outbreaks of illnesses of unknown etiology typified by a chronic relapsing course
      of constitutional symptoms and nervous system involvement have collectively been
      referred to as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic
      encephalomyelitis. To examine heterogeneity of clinical presentation, a
      comparative review was undertaken for 12 well-documented outbreaks reported since
      1934. A systemic syndrome characterized by excessive fatigue, myalgias, headache,
      low-grade fever, and other constitutional symptoms was common to cases in all
      outbreaks. However, marked heterogeneity in the range of neurological features
      was apparent. On the basis of predominant neurological manifestations, outbreaks
      could be grouped into four levels of increasing neurological involvement:
      affective neuropsychological changes (level I); prominent cutaneous sensory
      symptoms with both affective and cognitive neuropsychological changes (level II);
      marked objective paresis with cutaneous sensory as well as affective and
      cognitive neuropsychological changes (level III); and cutaneous sensory,
      affective and cognitive neuropsychological, posterior column, cranial nerve, and
      mixed upper and lower motor neuron changes (level IV). Groups with the most
      prominent objective neurological findings (levels III and IV) comprised
      exclusively outbreaks reported between the 1930s and 1950s. All but one outbreak
      in groups with less prominent neurological findings (levels I and II) were
      reported between the 1960s and 1980s; a range of neurological features was
      observed for these groups. Because a complete neurological examination is not
      emphasized as part of the diagnostic workup in current outbreaks, it is possible
      that less obvious neurological findings may be overlooked. Careful evaluation of
      neurological features in epidemic and endemic cases of what is now called chronic
      fatigue syndrome may be one approach to distinguishing subtypes of what has been
      described in the past as a nosological entity.

PMID- 8148452
TI  - Concurrent sick building syndrome and chronic fatigue syndrome: epidemic
      neuromyasthenia revisited.
AB  - Sick building syndrome (SBS) is usually characterized by upper respiratory
      complaints, headache, and mild fatigue. Chronic fatigue syndrome (CFS) is an
      illness with defined criteria including extreme fatigue, sore throat, headache,
      and neurological symptoms. We investigated three apparent outbreaks of SBS and
      observed another more serious illness (or illnesses), characterized predominantly
      by severe fatigue, that was noted by 9 (90%) of the 10 teachers who frequently
      used a single conference room at a high school in Truckee, California; 5 (23%) of
      the 22 responding teachers in the J wing of a high school in Elk Grove,
      California; and 9 (10%) of the 93 responding workers from an office building in
      Washington, D.C. In those individuals with severe fatigue, symptoms of mucous
      membrane irritation that are characteristic of SBS were noted but also noted were
      neurological complaints not typical of SBS but quite characteristic of CFS. We
      conclude that CFS is often associated with SBS.

PMID- 8148453
TI  - An approach to studies of cancer subsequent to clusters of chronic fatigue
      syndrome: use of data from the Nevada State Cancer Registry.
AB  - Chronic fatigue syndrome (CFS) has been increasingly associated with immune
      dysregulation, including depressed natural killer cell activity; this phenomenon
      is associated with increased susceptibility to cancer. Although anecdotal reports
      have suggested an association between CFS and cancer, particularly non-Hodgkin's
      lymphoma and brain cancer, there has been no a priori justification for
      evaluating such an association and no consideration of relevant parameters, such
      as length of latent period vs. tumor type. We reviewed data from the Nevada State
      Cancer Registry subsequent to a reported outbreak of a CFS-like illness in Nevada
      that occurred during 1984-1986. We concentrated on non-Hodgkin's lymphoma and
      brain/CNS tumors, with particular emphasis on persons 15-34 and 35-54 years of
      age. An upward trend in the incidence of brain/CNS tumors, which could be related
      to a national upward trend for this disease, was noted. No consistent trends were
      noted for non-Hodgkin's lymphoma. Because of the difficulties inherent in studies
      of cancer subsequent to various exposures, we evaluated the methodology for
      determining an association between outbreaks of CFS-like disease and cancer. We
      propose several approaches that should be considered in future studies for
      investigation of possible associations between CFS and cancer, including expected
      latent periods for specific tumors.

PMID- 8148454
TI  - Epidemiology of chronic fatigue syndrome.

PMID- 8148455
TI  - Acylcarnitine deficiency in chronic fatigue syndrome.
AB  - One of the characteristic complaints of patients with chronic fatigue syndrome
      (CFS) is the skeletal muscle-related symptom. However, the abnormalities in the
      skeletal muscle that explain the symptom are not clear. Herein, we show that our
      patients with CFS had a deficiency of serum acylcarnitine. As carnitine has an
      important role in energy production and modulation of the intramitochondrial
      coenzyme A (CoA)/acyl-CoA ratio in the skeletal muscle, this deficiency might
      induce an energy deficit and/or abnormality of the intramitochondrial condition
      in the skeletal muscle, thus resulting in general fatigue, myalgia, muscle
      weakness, and postexertional malaise in patients with CFS. Furthermore, the
      concentration of serum acylcarnitine in patients with CFS tended to increase to
      the normal level with the recovery of general fatigue. Therefore, the measurement
      of acylcarnitine would be a useful tool for the diagnosis and assessment of the
      degree of clinical manifestation in patients with CFS.

PMID- 8148456
TI  - Sleep disorders in patients with chronic fatigue.
AB  - This prospective, cohort study examined the prevalence of sleep disorders among
      highly selected patients with chronic fatigue. On the basis of responses
      suggestive of sleep pathology on a screening questionnaire, 59 patients from a
      university-based clinic for chronic fatigue who had undergone a medical and
      psychiatric evaluation underwent polysomnography. Criteria for chronic fatigue
      syndrome (CFS) were met by 64% of patients and those for a current psychiatric
      disorder were met by 41%. Overall, 41% of patients had abnormal results for a
      multiple sleep latency test and 81% had at least one sleep disorder, most
      frequently sleep apnea (44%) and idiopathic hypersomnia (12%). In comparing
      patients who did and did not meet CFS criteria, no significant differences were
      found in individual sleep symptoms or sleep disorders. Likewise, symptoms and
      sleep disorders were unrelated to psychiatric diagnoses. In conclusion,
      chronically fatigued patients with suggestive symptoms may have potentially
      treatable coexisting sleep disorders that are not associated with meeting
      criteria for CFS or a current psychiatric disorder.

PMID- 8148457
TI  - Psychosocial correlates of illness burden in chronic fatigue syndrome.
AB  - We related reported physical symptoms, cognitive appraisals (e.g., negative style
      of thinking), and coping strategies (e.g., denial/disengagement strategies) with
      illness burden across several functional domains separately in subsets of chronic
      fatigue syndrome (CFS) patients with (n = 26) and without (n = 39) concurrently
      diagnosed major depressive disorder (MDD). In regard to cognitive appraisal
      measures, automatic thoughts and dysfunctional attitudes were strongly associated
      with a higher illness burden, as indicated in sickness impact profile (SIP)
      scores. Active-involvement coping strategies measured on COPE scales (active
      coping, planning, and positive reinterpretation and growth) were not associated
      with SIP scores, while other coping strategies (mental disengagement, behavioral
      disengagement, and denial) were positively correlated with psychosocial and
      physical SIP scales, especially those pertaining to interpersonal life-style
      arenas. After we accounted for the number of different CFS-specific physical
      complaints reported and DSM-III-R depression diagnosis status, cognitive
      appraisals and coping strategies predicted a substantial proportion of the
      variance in the severity of illness burden. For the most part, the magnitude of
      these relationships between our predictor model variables and illness burden
      severity was similar in the MDD and non-MDD subgroups.

PMID- 8148458
TI  - Measuring the functional impact of fatigue: initial validation of the fatigue
      impact scale.
AB  - The fatigue impact scale (FIS) was developed to improve our understanding of the
      effects of fatigue on quality of life. The FIS examines patients' perceptions of
      the functional limitations that fatigue has caused over the past month. FIS items
      reflect perceived impact on cognitive, physical, and psychosocial functioning.
      This study compared 145 patients referred for investigation of chronic fatigue
      (ChF) with 105 patients with multiple sclerosis (MS) and 34 patients with mild
      hypertension (HT). Internal consistency for the FIS and its three subscales was >
      .87 for all analyses. Fatigue impact was highest for the ChF group although the
      MS group's reported fatigue also exceeded that of the HT group. Discriminant
      function analysis correctly classified 80.0% of the ChF group and 78.1% of the MS
      group when these groups were compared. This initial validation study indicates
      that the FIS has considerable merit as a measure of patient's attribution of
      functional limitations to symptoms of fatigue.

PMID- 8148459
TI  - Cognitive functioning of patients with chronic fatigue syndrome.
AB  - Neuropsychological problems are a distressing and frequent component of the
      symptom complex associated with chronic fatigue syndrome. Objective assessment of
      these difficulties is essential to understanding the nature of this illness.
      Results of the studies discussed in this paper suggest that impaired information
      processing, rather than primary memory dysfunction, may be at the root of the
      cognitive problems that afflict so many patients with CFS.

PMID- 8148460
TI  - A controlled clinical trial with a specifically configured RNA drug,
      poly(I).poly(C12U), in chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is a physically debilitating illness associated
      with immunologic abnormalities, viral reactivation, and impairment of cognition.
      In a randomized, multicenter, placebo-controlled, double-blind study of 92
      patients meeting the CFS case definition of the Centers for Disease Control and
      Prevention, the response of several laboratory and clinical variables to an
      antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined. Measures
      of clinical response included Karnofsky performance score, a cognition scale
      derived from a self-administered instrument assessing symptomatology (SCL-90-R),
      an activities of daily living scale, and exercise treadmill performance. After 24
      weeks, patients receiving poly(I).poly(C12U) had higher scores for both global
      performance and perceived cognition than did patients receiving placebo. In
      particular, patients given poly(I).poly(C12U) had increased Karnofsky performance
      scores (P < .03), exhibited a greater ability to do work during exercise
      treadmill testing (P = .01), displayed an enhanced capacity to perform the
      activities of daily living (P < .04), had a reduced cognitive deficit (P = .05),
      and required less use of other medications (P < .05).

PMID- 8148461
TI  - Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with
      chronic fatigue syndrome.
AB  - Levels of 2',5'-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L
      were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15
      individuals with chronic fatigue syndrome (CFS) before and during therapy with
      the biological response modifier poly(I).poly(C12U) and were compared with levels
      in healthy controls. Patients differed significantly from controls in having a
      lower mean basal level of latent 2-5A synthetase (P < .0001), a higher
      pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy
      RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean
      basal level of activated 2-5A synthetase higher than the corresponding control
      value (P = .009). All seven pretherapy PBMC extracts tested were positive for the
      replication of human herpesvirus 6 (HHV-6). Therapy with poly(I).poly(C12U)
      resulted in a significant decrease in HHV-6 activity (P < .01) and in
      downregulation of the 2-5A synthetase/RNase L pathway in temporal association
      with clinical and neuropsychological improvement. The upregulated 2-5A pathway in
      CFS before therapy is consistent with an activated immune state and a role for
      persistent viral infection in the pathogenesis of CFS. The response to therapy
      suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this
      situation.

PMID- 8148462
TI  - Molecular events in the activation of human neutrophils for microbial killing.
AB  - Human neutrophils provide protection from a variety of microbes; neutropenia or
      neutrophil dysfunction can both have serious clinical consequences. Effective
      microbial killing involves attachment to blood vessel walls, transmigration into
      tissues, chemotaxis, and phagocytosis. The molecular mechanisms by which
      neutrophils kill microbes have been extensively dissected. Each of the cellular
      processes is initiated in response to the occupancy of unique surface receptors.
      Receptor occupancy is translated into specific cellular activities via such
      signals as activation of calcium-mediated protein kinases and phosphorylation of
      critical proteins. After phagocytosis, the engulfed particle is subjected to
      killing mechanisms, which include reactive oxygen species, acid pH, and
      antimicrobial proteins. A thorough understanding of these molecular events may
      allow the modulation of neutrophil activity.

PMID- 8148463
TI  - Potential role of colony-stimulating factors in the prevention and treatment of
      infectious diseases.
AB  - The colony-stimulating factors (CSFs) principally involved in the production of
      neutrophils and monocytes are granulocyte CSF, granulocyte-macrophage CSF,
      macrophage CSF, and interleukin 3 (sometimes called multi-CSF). The natural
      response to inflammation and infection in the immunocompetent host probably
      involves all of these CSFs. CSFs can be used as pharmacological agents to
      accelerate the production of neutrophils and monocytes/macrophages and to enhance
      mechanisms of host defense. Rapidly accumulating evidence appears to justify the
      use of CSFs for the prevention of fever and infections in several clinical
      settings, such as chemotherapy-associated neutropenia, bone marrow
      transplantation, and severe chronic neutropenia. Trials of CSF treatment of
      infections in settings not including neutropenia are under way.

PMID- 8148464
TI  - Pathogenesis and potential strategies for prevention and treatment of septic
      shock: an update.
AB  - Septic shock is mediated by complex interactions of cells, cytokines, and humoral
      pathways. Clinical therapeutic strategies aimed at inhibiting selected pathways
      have been efficacious in subsets of patients. Experimental studies focusing on
      the activities of single cytokines have contributed to the understanding of the
      complex pathophysiology of septic shock. More precise delineation of the roles of
      each mechanism contributing to pathogenesis will permit the identification of
      subsets of patients who might benefit from particular therapeutic strategies and
      will guide the development of additional approaches to prevention and treatment.

PMID- 8148465
TI  - Platelet-activating factor biosynthesis in rat vascular smooth muscle cells.
AB  - The ability of platelet-activating factor (PAF) receptor antagonists to protect
      rats from the cardiovascular collapse induced by large doses of endothelin 1 led
      us to examine the capacity of rat cultured vascular smooth muscle cells to
      produce PAF and also to evaluate its potential functional roles in this cell
      type. Adenosine triphosphate and the vasoactive peptides, endothelin 1,
      angiotensin II, and arginine vasopressin, each elicited an increase in the PAF
      level in extracts of rat cultured vascular smooth muscle cells as determined by
      bioassay. PAF was not detectable (above 20 fmol/mg protein) in the supernatants
      of these cells. The identity of the bioactivity as PAF was confirmed by GC/MS
      which indicated that more than 80% of the PAF was 1-O-hexadecyl-2-acetyl-3-sn
      glyceryl-phosphorylcholine. Exogenous PAF (100 nM) elicited increases in
      intracellular calcium that were inhibited by WEB 2086 (10 microM). Endothelin 1,
      at a concentration which stimulated PAF synthesis, (1 nM), elicited increases in
      intracellular calcium levels that were not inhibited by WEB 2086 (10 microM).
      Thus, endogenous PAF is unlikely to be involved in the endothelin-1-induced
      calcium increases. Although WEB 2086 (3-100 microM) inhibited concentration
      dependently fetal calf serum (10% v/v) induced [3H]-thymidine incorporation,
      reaching a maximum effect at 30 microM of 40-50% reduction, in parallel
      experiments WEB 2086 had no effect on serum-induced increases in cell numbers. We
      conclude that PAF is produced and retained by cultured rat vascular smooth muscle
      and that it is unlikely to contribute to the signaling of increases in
      intracellular calcium or proliferation.

PMID- 8148466
TI  - In the normal rabbit femoral artery increasing arterial wall injury does not lead
      to increased intimal hyperplasia.
AB  - Angioplasty inflicts damage to the arterial wall. We studied whether augmented
      medial smooth muscle cell necrosis leads to augmented intimal hyperplasia and
      thus aggravates restenosis. Sixty-three normal femoral arteries of New Zealand
      White rabbits were overstretched with an angioplasty balloon during either
      maximal vasoconstriction with phenylephrine (32 arteries) or maximal vasodilation
      with nitroprusside (31 arteries). After 3 days' survival, medial necrosis was
      determined as percentage of cross-sectional medial area. In the 3 weeks' survival
      group, intimal hyperplasia was quantified as its average thickness. The dilation
      ratios, i.e. balloon diameter divided by arterial diameter at the time of
      dilation, were significantly higher in the 3 days' and 3 weeks' vasoconstriction
      groups (VC groups), respectively: 1.96 +/- 0.10 (mean +/- SD) and 2.14 +/- 0.08
      in the VC groups versus 1.27 +/- 0.03 and 1.32 +/- 0.05, respectively, in the
      vasodilation groups (VD groups) (both p < 0.001). Medial necrosis was more
      extensive in the VC group (64 +/- 5%) than in the VD group (23 +/- 7%, p < 0.001)
      and proportional to the dilation ratio (r = 0.69, p < 0.01). Intimal hyperplasia,
      however, was equal in the VC (59 +/- 8 microns) and VD (57 +/- 6 microns, NS)
      groups and not dependent on dilation ratio (r = 0.10). Thus, extensive medial
      necrosis produced during balloon dilation in maximally vasoconstricted arteries
      did not lead to more intimal hyperplasia than when less medial necrosis was
      induced by balloon dilation during vasodilation.

PMID- 8148467
TI  - Angiotensin-II-induced expression of laminin complex and laminin A-chain-related
      transcripts in vascular smooth muscle cells.
AB  - Laminin, a major structural glycoprotein complex of basement membranes has been
      found to be modulated by angiotensin II in vitro and in vivo. In cultures of
      aortic organoids and vascular smooth muscle cells, expression of laminin was
      stimulated by exogenous vasoconstrictor peptide. Stimulation of laminin protein
      and mRNA expression was observed for both laminin B1/B2-chains and an unknown
      laminin heavy chain. Compared with PYS-2 cells, a mouse teratocarcinoma cell line
      which constitutively expresses a 10-kb mRNA transcript for 'classical' laminin A
      chain, cultured vascular smooth muscle cells (VSMC) did not express a
      corresponding mRNA. However, cultured VSMC were found to express laminin A-chain
      related mRNAs of approximately 1.8 kb and approximately 3.8 kb, respectively. The
      1.8-kb species of transcript was expressed in a constitutive manner, whereas the
      3.8-kb mRNA was found to be regulated by angiotensin II. Laminin complexes
      secreted by cultured cells contained a approximately 300 kD heavy chain which did
      not immunoreact with immunoreagents raised against either the classical laminin
      complex secreted by EHS tumor cells or the merosin heavy chain. The putative A
      chain analogue possibly represents a new form of a tissue-specific laminin heavy
      chain, distinct from the A- and M-chains thus far described. Translation products
      encoded by the A-chain-related transcripts of cultured smooth muscle cells could
      not be specified using currently available antibodies. The putative protein(s) is
      speculated to contain the biological features of the N-terminus of the laminin A
      chain, namely self-assembly and association with collagen type IV.

PMID- 8148468
TI  - Thrombin generation following arterial injury is a critical initiating event in
      the pathogenesis of the proliferative stages of the atherosclerotic process.
AB  - Vascular injury, activation of the coagulation system and thrombosis are common
      initial events in the accelerated atherosclerotic process. The role of thrombin
      generated at the site of aortic injury in the subsequent neointimal proliferation
      was studied in rabbits (n = 16) 3 weeks after balloon catheter injury. In half of
      these animals, potent thrombin antagonists, r-hirudin and P-PACK, were
      administered to prevent acute thrombotic events. Compared to aortas with intact
      endothelium (n = 8), aortas de-endothelialised 21 days earlier showed neointimal
      hyperplasia as measured by the intimal/medial ratio (0.68 vs. 0.04, injured vs.
      normal aortas) and an increase in both total cholesterol (4.08 vs. 3.31 mg/g, p <
      0.05) and lipid peroxide content (31.3 vs. 1.1 nmol/g; p < 0.001). Neointimal
      hyperplasia following endothelial denudation was inhibited in rabbits treated
      with thrombin-antagonists (0.27 vs. 0.68, treated vs. untreated, p = 0.012) and
      neither total cholesterol (3.48 mg/g) nor lipid peroxide content (1.5 nmol/g)
      differed significantly from that of intact arteries. By demonstrating a strong
      relationship between thrombin generation following de-endothelialisation and the
      progressive intimal proliferation, this study supports the hypothesis that
      thrombin is an important contributor to restenosis after vascular injury. The
      highly atherogenic lipid peroxidation seems to be linked to the early, thrombin
      mediated events, as it was completely prevented by adequate thrombin antagonism.

PMID- 8148469
TI  - A new consistent model explaining structure (conformation)-activity relationships
      of opiates with mu-selectivity.
AB  - Several different classes of opiates such as PET (7-alpha-(1-Hydroxy-1-methyl-3
      phenylpropyl)-6,14-endo-ethenotetra - hydronorthebaine), phenazocine, fentanyl,
      carfentanil, ohmefentanyl, prodine derivatives, methadone and etonitazene have
      been investigated using the molecular modelling program package SYBYL and the
      TRIPOS empirical force field. Comparison of the energetically optimized
      structures and their corresponding molecular electrostatic potentials was used
      for the development of a new model of conformation-activity relationships of mu
      selective opiates. We considered six important spatial positions of these
      molecules which were assumed to be directly implicated in the interaction with
      the opiate receptor. We found that these opiates may bind to the receptor with
      their protonated nitrogen atom assuming one or the other of two different
      orientations. The obtained results offer new insights into important receptor
      interactions and the diverse opiate activities of all the compounds examined can
      be explained in a unified manner. For example, the most active ohmefentanyl
      stereo-isomer was predicted on the basis of the proposed model.

PMID- 8148470
TI  - Classification of serine proteases derived from steric comparisons of their
      active sites.
AB  - The steric arrangements of the amino acyl residues in the catalytic triads and
      tetrads of the active site are compared with each other by means of systematic
      analysis of the conformation of the serine proteases stored in the Brookhaven
      Protein Data Bank. On this basis a differentiation between the representatives of
      the (chymo)trypsin family on the one hand and those of the subtilisin family on
      the other hand is found. The enzyme tonin distinguishes from representatives of
      the (chymo)trypsin family and should be classified to a new subclass of this
      family. Thermitase represents a new subclass of the subtilisins. The spatial
      orientation of the amino acyl residues of the active site of tonin suggests a new
      mechanism of enzyme catalysis that possibly also occurs in dipeptidyl peptidase
      IV.

PMID- 8148471
TI  - Synthesis and cardiodepressant activity of dialkyl 1,4-dihydro-2,6-dimethyl-4
      (pentatomic-heteroaryl)-3,5-pyridine-dicarbo xylates. 2.
AB  - A new series of 1,4-dihydropyridine bearing substituted pyrazole and imidazole at
      C-4 position was synthesized and characterized as inotropic, chronotropic and
      calcium antagonist agents, in order to evaluate the effect on pharmacological
      activity of replacement of the 4-aryl group of nifedipine-like drugs by pyrazole
      and imidazole moieties. All compounds were tested on myocardial muscle and
      vascular smooth muscle of guinea-pigs. The new compounds showed both significant
      selective negative inotropic activity and fairly good negative chronotropic
      effects. All compounds elicited weak calcium antagonist activity, except compound
      9 which is a selective bradycardic agent.

PMID- 8148472
TI  - Dibenzothiazepinones as potential calcium channel antagonists. I.
AB  - Certain dibenzo[a,d]cycloheptenes and dibenzo[b,e]thiepins (e.g., 1 and 2)
      substituted in the 5 and 11-positions, respectively, are potent calcium channel
      antagonists. It has previously been shown that potency increases with a decrease
      in the angle between the planes of the flanking aromatic rings, as computed by
      semi-empirical AM1 calculations with geometry minimization. In the present study,
      we evaluated a series of dibenzo[b,f]-1,4-thiazepinones (10-14) as potential
      bioisosteres of these compounds having a slightly more acute angle of flexure. X
      Ray diffraction reveals the crystal structure of the parent dibenzo[b,f]-1,4
      thiazepinone 4 to have a flexure angle of 108.4 degrees. Due to electron
      delocalization, the amide moiety in the seven-membered ring adopts a planar
      conformation. The synthesis of a series of 10-[omega-[4-(4-fluorophenyl)piperazin
      1-yl]alkyl]dibenzo[b,f]-1,4 - thiazepin-11(10H)-ones (10-14), and results of
      their evaluation for calcium channel antagonistic activity on hamster aorta, are
      presented.

PMID- 8148473
TI  - Evaluation of the conjugate between N4-(4-carboxybutyryl)-1-beta-D
      arabinofuranosylcytosine and chitosan as a macromolecular prodrug of 1-beta-D
      arabinofuranosylcytosine.
AB  - The conjugate of N4-(4-carboxybutyryl)-1-beta-D-arabinofuranosylcytosine (glu-ara
      C) with chitosan, named chi-glu-ara-C, was prepared and evaluated on its utility
      as a macromolecular prodrug. 1-beta-D-Arabinofuranosylcytosine (ara-C) was
      predominantly regenerated gradually from chi-glu-ara-C in 1/15 M phosphate
      buffer, pH 7.4, at 37 degrees C, and its amount after 7 d incubation was 56%
      (w/w). The antitumor effect was evaluated by an increase in the lifespan (ILS) of
      the mice bearing P388 leukemia at the single administration at 24 h after
      inoculation. Ara-C exhibited an ILS of 3.4% at a dose of 100 mg/kg, and the
      survival time was not significantly different from that of the control. However,
      chi-glu-ara-C showed an ILS of 60.7% at a dose of 88 mg eq ara-C/kg, and the
      survival time was significantly different from that of the control. Chitosan and
      chi-glu-ara-C were observed to cause the side effects judged from the body weight
      loss to a certain extent. However, chi-glu-ara-C was recognized to be useful
      because of its effectiveness.

PMID- 8148474
TI  - Thrombogenic mechanisms in the human: fresh insights obtained by immunodiagnostic
      studies of coagulation markers.
AB  - Although in vitro studies have been invaluable in revealing the complex
      biochemistry of the blood coagulation system, meaningful in vivo studies of
      thrombogenic mechanisms have previously been hindered by the absence of suitable
      assays. This article reviews the recent development and/or contemporary clinical
      application of plasma-based immunoassays for coagulation markers (factor XIIa,
      factor IX activation peptide, prothrombin fragment F1 + 2, thrombin-antithrombin
      complex and fibrinopeptide A) and for the fibrinolytic marker, D-dimer, which
      have enabled a critical re-appraisal of some long-standing hypotheses. In chronic
      renal disease the intrinsic coagulation pathway was found to be activated before
      haemodialysis and increased end-stage coagulation activity was detected during
      dialysis when heparinization was limiting. No evidence was found to support the
      generally accepted hypothesis that thrombogenesis in dialysis is triggered by
      stimulation of the contact system following exposure of blood to the dialyser
      membrane. Instead, it is postulated that it is a failure of regulation of end
      stage coagulation proteinases (owing to the absence of endothelium) which is
      responsible for increased thrombogenesis in the dialyser circuit. Excessive end
      stage coagulation activity was observed during cardiopulmonary bypass (CPB)
      surgery and in patients undergoing general thoracic surgery. The data did not
      accord with the hypothesis that the contact system provides the major
      thrombogenic trigger in CPB surgery. It is proposed that, in general thoracic
      surgery, a powerful procoagulant stimulus is provided via the tissue factor
      factor VIIa pathway and that the same mechanism is also primarily responsible for
      triggering thrombogenesis during CPB surgery. The established hypothesis of a
      prethrombotic state in hereditary AT III deficiency is challenged by the
      inability to detect increased coagulation activity in asymptomatic AT III
      deficient patients. It is concluded that the AT III concentration in deficient
      members is sufficient to enable regulation of the coagulation system in the basal
      state, whereas failure to regulate the coagulation system only occurs following a
      major procoagulant stimulus, which overwhelms the impaired inhibitory capacity
      and triggers thrombosis. These findings highlight the advantages of using plasma
      based immunoassays to investigate thrombogenic mechanisms in hypercoagulable
      states and have important implications for the further study and treatment of
      blood-surface interactions and thrombotic disease.

PMID- 8148475
TI  - Biological effects of a S/D-treated, very high purity, von Willebrand factor
      concentrate in five patients with severe von Willebrand disease.
AB  - A highly purified von Willebrand factor (vWf) concentrate with low factor VIII
      (FVIII) content was tested to evaluate its biological effects in five patients
      with severe von Willebrand disease (vWd). The patients were infused with a single
      dose of this product corresponding to approximately 65 IU vWf:RCo and
      approximately 11 IU FVIII:C/kg and were followed up for 48 h. The plasma levels
      of FVIII and vWf and the multimeric pattern of vWf were determined before and 1,
      3, 6, 12, 24 and 48 h after infusion. In all patients the recovery (93 +/- 14%)
      and half-life (13 +/- 1 h) of vWf were consistent and normal and sustained FVIII
      levels were attained. In four patients both the duration and the volume of shed
      blood were measured after one incision with a standardized template method of
      bleeding time (BT). The duration of bleeding was completely corrected in two out
      of the four patients and partially corrected in the other two while the volume of
      shed blood was completely corrected in three patients and partially corrected in
      the fourth. However, the time for correction of both BT parameters was variable
      between patients. These data indicate that the vWf concentrate can correct the
      quantitative defects related to plasma vWf deficiency in vWd patients whereas the
      effect on template BT is less reproducible.

PMID- 8148476
TI  - Recombinant factor VIIa for intracranial haemorrhage in a Jehovah's Witness with
      severe haemophilia A and factor VIII inhibitors.
AB  - A Jehovah's Witness with severe haemophilia A and a high titre, high responding
      inhibitor to both human and porcine factor VIII (FVIII) was treated with
      recombinant activated factor VII (rVIIa) during an episode of intracranial
      bleeding. He recovered completely without any adverse effects or neurological
      sequelae. Treatment with rVIIa in this case was safe and effective. This
      therapeutic agent should be considered in haemophilia patients with inhibitors
      who refuse management with blood products on religious grounds and when
      recombinant factor VIII is not a cost-effective option.

PMID- 8148477
TI  - Acquired haemophilia in association with type III von Willebrand's disease:
      successful treatment with high purity von Willebrand's factor and recombinant
      factor VIIa.
AB  - A patient with autosomal dominant (Type III) von Willebrand's disease (vWd)
      developed acquired haemophilia post-operatively, possibly due to exposure to
      amoxycillin. She refused porcine factor VIII (pFVIII) on religious grounds and
      was managed successfully with recombinant activated factor VII (rFVIIa) together
      with highly purified von Willebrand factor concentrate (vWf-VHP). In patients
      with acquired haemophilia rFVIIa appears to be a suitable agent for symptomatic
      management.

PMID- 8148478
TI  - Recombinant streptokinase: opportunity for an improved agent.

PMID- 8148479
TI  - Protein C, factor VII and prothrombin time as early markers of liver function
      recovery or failure after liver transplantation.
AB  - Irreversible initial non-function of the graft liver is a life-threatening early
      complication of orthotopic liver transplantation (OLT), which needs immediate
      retransplantation if the patient is to survive. Since protein C (PC) is a vitamin
      K dependent protein synthesized in the liver and with the same half-life as
      factor VII (FVII), the behaviour of PC in patients undergoing OLT was studied in
      comparison with prothrombin time (PT) and FVII. Twelve OLT patients were divided
      into two groups on the basis of clinical outcome: group A (six cases) in which
      OLT was successful, and group B (six cases) who developed initial non-function of
      the graft liver. PT, FVII activity (FVII:act) and antigen (FVII:Ag) and PC
      activity (PC:act) and antigen (PC:Ag) were carried out on six blood samples
      collected during the operation. At baseline, coagulation disorders were in
      agreement with the underlying liver disease, but no differences were seen between
      the two groups when all tests were considered. Ten minutes, 1, 2 and 3 h after
      liver reperfusion, mean PT and FVII:act were always significantly increased in
      good responder patients compared to non-responders. FVII:Ag and PC:Ag were
      significantly higher in group A than in group B starting 2 h after the liver
      graft reperfusion; no difference was seen in PC:act levels between the two
      groups. In addition, PC:Ag mean levels were increased with respect to
      corresponding PC:act values in non-responder patients, suggesting a qualitative
      rather than quantitative defect of protein synthesis due to liver damage. In
      conclusion, PT and FVII:act were more sensitive than PC activity as early
      prognostic indices of clinical outcome in OLT.

PMID- 8148480
TI  - Modulation of procoagulant activity of extracellular endothelial matrix by anti
      tissue factor antibody and the synthetic peptide Arg-Gly-Asp-Val. Experiments
      with flowing non-anticoagulated human blood.
AB  - Fibrin forms on and binds to the extracellular matrix of endotoxin-stimulated
      endothelium when exposed to flowing non-anticoagulated blood. These processes
      have been investigated by employing a human ex vivo perfusion model, a synthetic
      peptide Arg-Gly-Asp-Val and a monoclonal anti-tissue factor antibody which
      inhibits tissue factor/FVIIa-induced coagulation. Procoagulant extracellular
      matrix on plastic cover-slips was prepared from cultures of endotoxin-stimulated
      human endothelium following brief exposure to 0.1 M NH4OH. Non-anticoagulated
      blood was drawn directly from an antecubital vein by a pump at venous (100/s) and
      arterial (650/s) wall shear rates over the matrix-coated cover-slips positioned
      in parallel-plate perfusion chambers. Deposition of fibrin and platelets on the
      matrix was quantified by morphometry. Preincubation of the matrix with Arg-Gly
      Asp-Val inhibited fibrin deposition by 80-90% at both venous (P < 0.001) and
      arterial shear (P < 0.05). However, the peptide had no effect on the clotting
      time in a modified one-stage clotting assay where coagulation was initiated by
      lysed endotoxin-stimulated endothelial cells, indicating that the peptide
      interfered with the binding of fibrin to the matrix in the perfusion model.
      Preincubation of the matrix with the anti-tissue factor antibody, which blocked
      the coagulant activity ( > 95%, P < 0.01) in the modified coagulation assay, also
      inhibited fibrin deposition on the matrix by 90-95% (P < 0.01) at both shear
      rates. In the absence of either inhibitor, platelets adhered preferentially to
      the fibrin meshwork, and more so at arterial shear. Platelet thrombus formation
      on the fibrin coat was in particular pronounced at arterial shear. Thus, it
      appears that the extracellular matrix of endotoxin-stimulated endothelium
      initiates coagulation predominantly through tissue factor/FVIIa and that the
      resulting fibrin meshwork forming on the surface induces rapid platelet thrombus
      formation. The inhibitory effect of Arg-Gly-Asp-Val on the binding of fibrin to
      the matrix may indicate the presence of specific matrix fibrinogen/fibrin binding
      site(s) with a recognition sequence of Arg-Gly-Asp.

PMID- 8148481
TI  - Fibrinolytic parameters during acute haematemesis in endemic hepatosplenomegaly.
AB  - Fibrinogen (Fg), plasminogen (Plg), alpha 2-antiplasmin (alpha 2-AP), plasminogen
      activator (PA), tissue plasminogen activator (tPA), plasminogen activator
      inhibitor (PAI), D-dimer (DD) and fibrin(ogen) degradation products (FDP) were
      studied in 60 subjects: 40 patients with endemic hepatosplenomegaly (20 during
      acute haematemesis from ruptured oesophageal varices, 20 with endemic
      hepatosplenomegaly assigned to the same grade of oesophageal varices but with no
      history of haematemesis) and 20 normal controls. All parameters were markedly
      altered in the disease groups. Reduced levels of Fg, Plg, alpha 2-AP and PAI were
      associated with increasing levels of PA, t-PA, DD and FDP. Alterations were most
      marked in the group complicated by acute bleeding. It was concluded that these
      patients have an enhanced fibrinolytic state. This was probably aggravated in the
      haematemesis group by an acute haemostatic imbalance that superimposed the low
      grade chronic DIC reported in cases of hepatosplenic schistosomiasis.

PMID- 8148482
TI  - Effect of synthetic phospholipids on the response of the activated partial
      thromboplastin time to heparin.
AB  - The activated partial thromboplastin time (aPTT) is the most popular test for
      monitoring of heparin therapy. The purpose of the present study was to show that
      an aPTT reagent with good response to heparin can be prepared from synthetic
      phosphoglycerides. Mixed liposomes were prepared from synthetic
      dioleoylphosphatidylserine (DOPS), dioleoylphosphatidylcholine (DOPC), and
      dioleoylphosphatidylethanolamine (DOPE). These liposomes were used in an aPTT
      test system with kaolin as activator, to evaluate their procoagulant activity in
      the absence and presence of heparin. For comparison, mixtures of purified non
      synthetic phospholipids were prepared and tested with the same systems. The aPTT
      and its response to heparin were influenced by the phospholipid class composition
      and concentration. The presence of phosphatidylserine (PS) was required to reduce
      the aPTT of normal plasma to values between 30 and 40s. The presence of
      phosphatidylethanolamine (PE) in mixed liposomes could modulate the response to
      heparin. At low PE/PS liposome concentrations (approximately 40 microM), a
      relatively low response was observed. At high liposome concentrations
      (approximately 1 mM), the response to heparin increased with the mole fraction of
      phosphatidylethanolamine. The results obtained with non-synthetic phospholipid
      mixtures were similar to those obtained with the synthetic phosphoglycerides.
      Optimal concentrations of DOPS, DOPE and DOPC were found with which an almost
      linear response to heparin and to low molecular weight heparin (Fragmin) was
      observed. Using a mixed liposome consisting of 12 microM DOPS/12 microM DOPC/16
      microM DOPE, a doubling of the base-line aPTT was achieved at approximately 0.2
      IU/ml of heparin, and at approximately 1.0 IU/ml of Fragmin.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8148483
TI  - Platelets contain releasable coagulation factor IX antigen.
AB  - Platelets take up plasma proteins into their alpha granules. Platelet activation
      releases the alpha granule contents. The goal of this study was to test the
      hypothesis that human platelets also contain some coagulation factor IX in their
      alpha granules. Platelets were examined by immunofluorescence microscopy.
      Activated and unactivated platelets were quick frozen on to slides and dehydrated
      in situ to preserve optimal morphology. The slides were stained by indirect
      immunofluorescence for factors V and IX. Unactivated platelets showed coarsely
      granular staining for factor V and finely granular staining for factor IX.
      Staining for factor V was diffuse after activation, while staining for factor IX
      disappeared. Thus, the results support the conclusion that platelets contain
      factor IX which can be released upon activation. Immunoelectron microscopic
      studies were conducted to more precisely localize the site of the platelet factor
      IX. As expected, factor V was primarily localized in the alpha granules of
      unactivated platelets. By contrast, factor IX was observed both in alpha granules
      and diffusely in the platelet cytoplasm and membrane-bounded vesicles. After
      activation, staining for both factors V and IX was primarily in the open
      canalicular system. The physiological importance of this small amount of factor
      IX is unknown. However, it may be significant since only a few percent of normal
      IX levels are required to support haemostasis in the absence of trauma, and
      platelet factor IX could be released at sites of active coagulation.

PMID- 8148484
TI  - Immunofluorescent studies of tissue factor on U87MG cells: evidence for non
      uniform distribution.
AB  - U87MG cells (human glioblastoma) express tissue factor and shed membrane-derived
      vesicles enriched in procoagulant activity. Tissue factor antigen has been
      studied by flow cytometry, immunofluorescent microscopy and Western blotting.
      Flow cytometric analysis utilized monoclonal antibodies recognizing the tissue
      factor extracellular domain and the carboxyl-terminal nine amino acids. Studies
      with intact and permeabilized cells support the location of the carboxyl-terminal
      domain in the cytoplasm, as previously predicted from the protein sequence.
      Immunofluorescent microscopy revealed a heterogeneous staining pattern,
      indicating that tissue factor antigen may be clustered on the cell surface.
      Intense staining was occasionally observed in cytoplasmic extensions and membrane
      regions that appeared to be extruding from the cells. Western blot analysis of
      vesicles shed into the culture medium revealed a principal tissue factor band
      with mobility marginally slower than that of placental tissue factor. Both
      extracellular and cytoplasmic epitopes were present in this vesicular tissue
      factor.

PMID- 8148485
TI  - Urinary protein C inhibitor binding region in the B beta-chain of human
      fibrinogen.
AB  - The urinary protein C inhibitor (PCI) binding region in the B beta-chain of human
      fibrinogen was examined by ligand blotting, reverse-phase HPLC and amino acid
      sequencing. The B beta-chain, isolated from reduced and pyridylethylated
      fibrinogen, was digested with staphylococcal V8 protease to yield eight peptides
      consisting of 10, 12, 13, 13.5, 14, 16, 17 and 18 kDa bands and the cleaved
      peptides were ligand-blotted. The 12 kDa band bound to urinary PCI. Moreover, the
      digested B beta-chain was isolated by reverse-HPLC and the elution peak showing
      positive binding to urinary PCI was sequenced. The N-terminal amino acid sequence
      was A V S Q T, which corresponds to Ala106-Thr110 in the B beta-chain. Judging
      from the M(r) of this peptide (12 kDa), it comprises the region from Ala106 to
      Glu192-Glu210 which are partly located in the D-region. It is concluded that the
      urinary PCI-binding region to the B beta-chain resides in the sequence of Ala110
      to Glu192-Glu210.

PMID- 8148486
TI  - Evidence for thrombin binding to dermatan sulphate sites in the rabbit aorta
      subendothelium in vitro.
AB  - The proposal that thrombin binds to dermatan sulphate chains of extracellular
      proteoglycans has been examined directly using the subendothelium of the rabbit
      aorta. Freshly excised aortas were de-endothelialized by balloon catheter in
      vitro and then incubated with 125I-thrombin to allow adsorption of 20-30 fmol of
      thrombin/cm2. Pretreatment of the subendothelium with FPR-thrombin or
      chondroitinase ABC partially inhibited thrombin binding, each by approximately 40
      45%. The addition of dermatan sulphate inhibited, competitively, up to 50% of
      thrombin from binding to the subendothelium whereas chondroitin-4 or -6 sulphates
      had little or no effect. By contrast, protamine inhibited 90% of FPR-thrombin
      binding. Of subendothelium-bound thrombin, chondroitinase ABC released only a
      small proportion (3-12%) of bound thrombin but up to 44% of bound FPR-thrombin.
      It is concluded that, when 125I-thrombin is bound in vitro at a concentration of
      < 30 fmol/cm2 of aorta intima-media, approximately 50% of subendothelial 125I
      thrombin is bound to dermatan sulphate chains of proteoglycan in the
      extracellular matrix. The possibility is discussed that dermatan sulphate chains
      may function as thrombin-binding loci to control or augment thrombin activity in
      the ECM of the injured vascular wall in vivo.

PMID- 8148487
TI  - The influence of tamoxifen in vivo on the main natural anticoagulants and
      fibrinolysis.
AB  - The long-term effects of tamoxifen on alterations in haemostasis which could lead
      towards thrombosis were investigated in 149 women who were disease-free for at
      least 5 years following mastectomy for breast cancer. All participants were
      randomized to receive tamoxifen as a post-surgical adjuvant treatment (89
      patients, treated group) or not (60 patients, controls) for at least 2 years.
      5.62% of the cases treated with tamoxifen suffered a venous thrombosis, while no
      thromboembolism was reported in the control group. No significant differences
      were observed between groups in the global clotting times, fibrinogen,
      fibrinolytic factors, or in the concentration of the main natural anticoagulants,
      antithrombin III (AT-III), protein C(PC) and protein S (PS). However, when the
      treated group was sub-divided, current users (n = 18) of the drug (median
      treatment duration 72 months) had significantly lower AT-III (P < 0.05) and PC (P
      < 0.05) activities, together with higher levels of plasminogen activity (P <
      0.01) and tissue plasminogen activator antigen (P < 0.01), compared with 71 ex
      users (who mostly received treatment for 2 years) and controls. We conclude that
      long-term treatment with tamoxifen for 2 or more years tends to reduce both AT
      III and PC, a situation possibly predisposing towards thrombosis. Monitoring
      haemostasis in tamoxifen-treated breast cancer patients is therefore advisable.

PMID- 8148488
TI  - The activation of factor VII in citrated plasma by charged long-chain saturated
      fatty acids at the interface of large triglyceride-rich lipoproteins.
AB  - The prolonged incubation of dilute plasma on ice in the presence of added
      sulphatide vesicles or the long-chain saturated fatty acids (FA) stearic acid
      (C18:0) or behenic acid (C22:0) induced a concentration-dependent increase in
      factor VII coagulant activity (VIIc). The addition of FA at various ratios to
      human serum albumin showed the micellar non-bound pool to be responsible for this
      effect, FA bound to the high-affinity or low-affinity binding sites of albumin
      having no influence on VIIc. Plasma VIIc also increased following addition of
      behenate-enriched lipoprotein particles produced by incubation of the d < 1.006
      g/ml lipoprotein fraction with this FA, or addition of lipoprotein remnants
      produced by pre-incubation of the d < 1.006 g/ml fraction with lipoprotein
      lipase. Long-chain saturated fatty acids in the interface of lipoprotein
      remnants, produced by the interaction of triglyceride-rich lipoprotein particles
      with lipoprotein lipase, appear to provide a surface that activates the contact
      system of coagulation and subsequently factor VII.

PMID- 8148489
TI  - Biology of factor IX.
AB  - Within the past 20 years or so, factor IX has been at the centre of particularly
      intensive studies of its physiology, pathology and biochemistry as well as its
      molecular genetics and biology. With the complete nucleotide sequence of its
      human gene determined in 1985 and the molecular defects of over 600 abnormal
      human factor IX genes analysed to date, factor IX is among the few mammalian
      proteins which have been exhaustively studied in almost every aspect. The
      enormous amount of information we now have on this medium-sized plasma protein
      sheds light on how a gene and its protein evolve, how the protein carries out a
      highly regulated, specific and pivotal role in the delicately balanced blood
      coagulation reaction, and the correlation between clinical presentations and its
      highly diverse molecular mechanism of defects. This wealth of knowledge makes
      factor IX an excellent model for deeper study, such as truly quantitative
      analysis of its structure-function relationship and in vivo function and
      regulation. It will also provide a sound foundation which may lead to improved
      treatment of haemophilia B and perhaps to its cure. This paper attempts to review
      the recent progress in research on factor IX.

PMID- 8148490
TI  - Post-receptor events associated with thrombin-induced platelet activation.
AB  - Thrombin is by far the most potent platelet agonist. Potentially this reflects
      multiple intracellular processes involved in transmitting the activation signal
      from the initial contact with a receptor, or binding site, to the final platelet
      response. Platelet membranes have two putative receptors: the high affinity
      glycoprotein Ib, whose function remains to be clarified, and the moderate
      affinity autoproteolytic receptor. The autoproteolytic receptor is a member of a
      family of receptors, with seven transmembrane domains, which interact with GTP
      binding proteins. Distal to the membrane, several forms of phospholipase C are
      activated and roles for both heterotrimeric and low molecular mass GTP-binding
      proteins have been presented. Phospholipase C acts on inositol phospholipids to
      generate inositol trisphosphate and diacylglycerol, both of which function as
      second messengers in thrombin-induced platelet activation. Inositol trisphosphate
      mobilizes internal calcium stores and this is accompanied, and enhanced, by an
      influx of calcium from the external milieu. Diacylglycerol and calcium both serve
      to regulate the activity of multiple protein kinases which, in turn, mediate the
      phosphorylated state of numerous proteins. Phosphorylation can occur on serine,
      threonine or tyrosine residues of target proteins and the phosphorylated state of
      these proteins determines the final activation of the platelet.

PMID- 8148491
TI  - The role of endotoxin immunity, neutrophil degranulation and contact activation
      in the pathogenesis of post-operative organ dysfunction.
AB  - Gut mucosal hypoperfusion is associated with a poor outcome following major
      surgery but the pathogenetic mechanisms remain poorly understood. We have
      examined the relationship between gut mucosal hypoperfusion, endotoxin core
      antibodies (EndoCAb), neutrophil elastase alpha-1 antitrypsin complexes (NE) and
      components of the contact system during elective major surgery. Of the 26
      patients studied 16 developed gut mucosal hypoperfusion (pHi < 7.32) by the end
      of surgery; of these four developed multiple organ failure (MOF) and three
      subsequently died. In this group there was a significant rise in NE (P < 0.005)
      and significant reductions in components of the contact system (factor XII,
      antithrombin III, prekallikrein and C1-inhibitor; P < 0.001) from immediately
      before surgery to 24 h later. Ten patients maintained gut mucosal perfusion (pHi
      > or = 7.32); none of these developed life threatening complications. In this
      group there was no significant increase in NE and, although there were
      significant reductions in some components of the contact system (P < 0.01),
      levels of C1-INH were not reduced. All patients demonstrated a significant
      reduction in both IgG and IgM EndoCAbs (P < or = 0.005) indicating exposure to
      endotoxin. However, the group that maintained gut mucosal perfusion had
      significantly higher IgG EndoCAb levels at baseline and 24 h (P < or = 0.005).
      These data suggest that all patients were exposed to endotoxin and that high
      levels of anti-endotoxin antibodies may contribute to the prevention of endotoxin
      induced contact activation, neutrophil degranulation and gut mucosal
      hypoperfusion occurring during major surgery and thus reduce the likelihood of
      the development of post-operative MOF.

PMID- 8148492
TI  - In vivo effects of purified recombinant human macrophage colony-stimulating
      factor in combination with local hyperthermia on tumor progression in B16a
      melanoma bearing mice.
AB  - Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was
      evaluated, alone or in combination with local hyperthermia (LH), for their
      antitumor effects in mice inoculated with B16a melanoma cells. Several tumor
      related parameters and other hematopoietic and immunologic parameters were
      evaluated 5 weeks after subcutaneous (s.c.) inoculation of tumor cells into the
      right limbs of C57BL/6J male mice. RhuM-CSF was administered at 20
      micrograms/injection, s.c., twice a day for 5 days/week for 2 weeks beginning 6
      days after tumor cell inoculation and LH (43 +/- 0.2 degrees C) was given for 30
      min twice/week for 2 weeks. Combined therapy prolonged survival of mice and
      caused significant inhibition of tumor growth, as measured by the volume or size
      of primary tumor, number and size of lung metastases, and chromatin fragment (CF)
      formation in tumor bearing mice, while treatment with M-CSF or LH alone had less
      or no effect. Combined therapy also resulted in increased numbers of splenic T
      lymphocytes and the ratio of T-helper/suppressor cells, restoration of natural
      killer (NK) cell activity, increased numbers of peritoneal macrophages and their
      erythrophagocytosis capacity, and increased release or production of tumor
      necrosis factor (TNF)-alpha, but not interleukin (IL)-1 alpha or IL-6. These
      results add to previous evidence that M-CSF might be a relevant therapeutic agent
      in combination with other therapies in the treatment of certain malignant
      diseases.

PMID- 8148493
TI  - Chromosomic findings in patients with paroxysmal nocturnal hemoglobinuria.
AB  - The chromosomes of 14 patients (9 males, 5 females) suffering from paroxysmal
      nocturnal hemoglobinuria in Merida, Mexico between April 1989 and July 1992 were
      analyzed. Four of the patients were children (range, 3-15 years old) and 9 were
      adults (range, 19-62 years old). None of the patients had any evidence of
      leukemic transformation and 9 of them had antecedent insecticide exposure. In
      50%, the clinical presentation was anemia plus hemorrhagic syndrome. Only 1 case
      had thrombosis. The lapse between the beginning of the disease and the karyotypic
      analysis was 14.5 months on average (range, 1-172 months). In all cases we found
      a normal chromosomic complement. In addition, 5 patients had an acentric fragment
      in only 1 metaphase and one of these had a mar and Cq chromatid break in another
      metaphase, but neither could be considered as specific chromosomal abnormality
      for paroxysmal nocturnal hemoglobinuria.

PMID- 8148494
TI  - Differential expression of fibronectin receptors during myeloid differentiation
      and in marrow- and peripheral blood-derived leukemic cells.
AB  - A 125I-labeled 120-kDa fibronectin fragment (FN120) containing the RGD binding
      site was employed to assess FN120 receptor levels in control and
      dimethylsulfoxide (DMSO)-differentiated HL60 cells, as well as in leukemic
      peripheral and bone marrow blast cells from acute lymphoid (ALL) and myeloid
      (AML) patients. Fibronectin CS1 fragment receptor alpha 4 (VLA4-alpha) and RGD
      dependent alpha 5 integrin subunits (VLA5-alpha) were characterized by specific
      monoclonal antibodies (MoAb). HL60 cells, induced along the granulocytic pathway
      with DMSO, displayed low FN120 binding level densities (36,070 +/- 5142
      sites/cell (s/c) vs. 19,780 +/- 4564 s/c, P < 0.005), respectively, for untreated
      and treated cells) together with decreased VLA5-alpha expression. Granulocytes
      displayed low levels of FN120 receptors (3167 +/- 1165 s/c) with weak VLA5-alpha
      expression and absence of VLA4-alpha. Normal lymphocytes displayed 17,670 +/-
      8,705 s/c FN120 receptors and VLA4-alpha and VLA5-alpha. The mean FN120 binding
      levels and mean VLA5-alpha expression were lower in peripheral blast cells, both
      in ALL and AML, than in the bone marrow leukemic cells. VLA4-alpha remained the
      same irrespective of cell localization. FN120 binding sites and differential
      expression of VLA4-alpha and VLA5-alpha integrin molecules on hemopoietic cells
      could be related to lineage characteristics or cell type distribution within
      hemopoietic tissue.

PMID- 8148495
TI  - Spinal epidural involvement in pleural lymphomas developing from long-standing
      tuberculous pyothorax or pleuritis.
AB  - Spinal epidural involvement was noted in 3 patients with pleural lymphoma
      developing from long-standing pyothorax or pleuritis. Two patients presented with
      cord compression syndrome and pleural tumor. The other patient showed rapidly
      progressive signs of cord compression 8 months after the diagnosis of pleural
      lymphoma. Biopsy and autopsy findings revealed that both the epidural masses and
      the pleural tumors had the pathological features of malignant lymphoma. Several
      reports have described pleural lymphomas complicated with chronic tuberculous
      pyothorax. However, as far as we know, there is no previous report associating
      spinal epidural compression with pyothorax-related pleural lymphoma. Spinal
      involvement should be included as a noteworthy complication of pleural lymphoma
      developing from long-standing tuberculous pyothorax.

PMID- 8148496
TI  - Reactivation of hepatitis B virus in two chronic GVHD patients after transplant.
AB  - We report two cases of hepatitis B virus reactivation following allogeneic bone
      marrow transplantation (BMT) for severe aplastic anemia and acute myelocytic
      leukemia. The presence of antibodies to HBsAg, HBeAg and HBcAg prior to
      transplant indicated previous infection with hepatitis B virus (HBV). These
      antibodies disappeared 2 and 4 months after the onset of chronic graft versus
      host disease (GVHD) following immunosuppressive treatment, but HBsAg reappeared
      in their sera 6 and 10 months later, respectively. This suggests that chronic
      GVHD and immunosuppressive drugs can reactivate HBV in HBsAb-positive patients,
      most likely because of the decrease in quality and function of helper T cells and
      B cells during chronic GVHD to induce clearance of HBV antibodies and
      reactivation of HBV. Our observation confirms that patients with HBsAb, HBeAb and
      HBcAb present in their sera should not be considered to have 'immunity' to HBV
      after BMT.

PMID- 8148497
TI  - Ultrastructural analysis of a human megakaryocytic leukemia cell line (CMK11-5)
      following prostaglandin E1 stimulation.
AB  - We examined the ultrastructural changes occurring in a human megakaryocytic
      leukemia cell line, CMK11-5, in response to stimulation with prostaglandin E1
      (PGE1). The addition of PGE1 to cultured cells dose-dependently caused vacuole
      enlargement, the development of cell surface projections, cell surface vacuole
      formation, and the release of a tracer protein (horseradish peroxidase) which had
      been incorporated into cytoplasmic granules. These morphological changes, which
      occurred parallel with [Ca2+]i mobilization in the CMK11-5 cells, were similar to
      those observed in CMK cells in response to stimulation with ADP, thrombin, and
      collagen. Our present findings suggest that PGE1 has a stimulatory effect on
      CMK11-5 cells through the induction of [Ca2+]i mobilization, and that the PGE1
      induced transmembrane signaling system in megakaryocytes is completely different
      from that in platelets.

PMID- 8148498
TI  - Flow cytometric analysis of surface membrane proteins on activated platelets and
      platelet-derived microparticles from healthy and thrombasthenic individuals.
AB  - We used flow cytometry to investigate surface membrane protein expression by
      platelets and platelet-derived microparticles from normal individuals and a
      patient with Glanzmann's thrombasthenia. Microparticles were detected by both
      forward scatter and side scatter using FACScan. The binding of coagulation
      factors on microparticles was investigated by using monoclonal anti-Factor IX
      (IXa) and anti-Factor X (Xa) antibodies. Furthermore, the procoagulant activity
      of microparticles was measured with a chromogenic substrate (S-2222) using a
      microtiter enzyme-linked immunosorbent assay. Both types of platelets showed
      similar release of microparticles. Microparticles released from platelets after
      activation with the calcium ionophore A23187 did not bind factors IXa and Xa, but
      when purified factors Va and Xa were added to the incubation buffer, factor Xa
      binding increased markedly in both normal and thrombasthenic platelets. Both
      normal and thrombasthenic platelets showed a similar time-dependent release of
      microparticles when activated with A23187. However, the binding of an antibody to
      granule membrane protein-140 also increased time-dependently in normal
      microparticles, but was little increased in thrombasthenic microparticles. These
      findings suggest that glycoprotein IIb/IIIa does not participate in the
      expression of prothrombinase activity on the surface of activated platelets and
      microparticles, whereas this glycoprotein appears to have an important role in
      the movement of granule membrane protein-140 from platelets to microparticles.

PMID- 8148499
TI  - Gene organization of human protein C inhibitor, a member of SERPIN family
      proteins encoded in five exons.
AB  - Protein C inhibitor (PCI), a plasma serine protease inhibitor, neutralizes
      activated protein C, which plays an important role in the regulation of blood
      coagulation. We determined the organization of the gene coding for this
      inhibitor. A human genomic phage DNA library was screened using the 32P-labeled
      protein C inhibitor cDNA as a probe and a phage genomic clone that contained the
      full length of the inhibitor gene, including the 5'- and 3'-flanking region, was
      isolated. The gene was characterized by restriction enzyme mapping, Southern
      blotting and sequencing all the coding parts as well as the 5'- and 3'-flanking
      regions. The protein C inhibitor gene spanned about 13 kilobase pairs and
      consisted of 5 exons and 4 introns as do the genes for human alpha 1-antitrypsin,
      alpha 1-antichymotrypsin, heparin cofactor II and rat angiotensinogen. All exon
      intron boundaries agreed with the GT-AG rule. The 5'-flanking region contained no
      TATAA or CCAAT sequences, but contained the putative Sp-1 and AP-2 binding sites
      in the 5'-upstream region, which indicated promoter activity in human hepatoma
      cell line, HepG2, using the luciferase gene as a reporter gene and the
      polyadenylation site in the 3'-downstream region. A transcription initiation site
      was identified by primer extension analysis using template human liver
      poly(A)RNA. The length of the non-coding exon I of this inhibitor gene was
      similar to those of the other serine protease inhibitors as described above.
      These findings suggest that the protein C inhibitor gene evolved from a common
      ancestor gene of these serine protease inhibitors.

PMID- 8148500
TI  - Time-course detection of HIV-1 proviral DNA and genomic RNA by polymerase chain
      reaction in sera from seropositive and seronegative hemophiliacs treated with
      clotting factor concentrates.
AB  - The detection of HIV-1 proviral DNA and genomic RNA was performed by polymerase
      chain reaction (PCR) in hemophiliacs treated with non-heated clotting factor
      concentrates. Reamplification with double PCR was performed on those samples that
      were negative for single PCR. Primer pairs of the gag, env, and pol regions were
      used for the amplification of HIV-1 proviral DNA sequences. Amplification of the
      gag region by the SK38/SK39 primer pair was useful for the detection of proviral
      DNA sequences. With double PCR, 44 of 47 seropositive samples (93.6%) were PCR
      positive. All 23 seronegative samples were PCR-negative. Reverse transcription
      and PCR amplification (RT-PCR) according to the primer pair of the gag region
      were performed to detect HIV-1 genomic RNA sequences. Double RT-PCR analysis of
      the HIV-1 RNA sequence in frozen-preserved sera revealed that 49 of 55
      seropositive sera (89.1%) were PCR-positive. Although quantification of the PCR
      method was not performed in this study, we concluded that, in patients in whom
      proviral DNA or genomic RNA sequences are detected with difficulty with PCR, the
      onset and progression of HIV-1 infection is delayed.

PMID- 8148501
TI  - Anterior aesthetic considerations for the placement and restoration of
      nonsubmerged endosseous implants.
AB  - Nonsubmerged endosseous dental implants should be considered when planning
      optimal anterior implant rehabilitation. Detailed diagnostic records are a
      necessity, along with preoperative and preprosthetic treatment plans that are
      designed to address the unique challenges of anterior restorations. This paper
      discusses these concerns and presents two case reports which utilize some of the
      techniques that can be incorporated into achieving predictable anterior aesthetic
      rehabilitation using a single-stage implant. The learning objective of this
      article is to familiarize the reader with those challenges and techniques.

PMID- 8148502
TI  - Soft tissue contouring for aesthetic single-tooth implant restorations.
AB  - The aesthetic replacement of a single anterior tooth has been revolutionized by
      the advent of dental implant technology. The learning objective of this article
      is to enhance the knowledge of single tooth restorations through the discussion
      of the restorative techniques, soft tissue management, and aesthetic
      considerations. The techniques presented can be used to obtain predictable
      results in the anterior region for aesthetic, hygienic, and functional
      restorations.

PMID- 8148503
TI  - Immediate postextraction placement of an alloplast and titanium screw implant: a
      seven-year case presentation.

PMID- 8148504
TI  - Aesthetic considerations for posterior single-tooth implant prosthetics: a case
      study.
AB  - The initial research in dental implantology was performed on fully edentulous
      anterior mandibles, and the results were disclosed in 1982 at the Toronto
      Conference. Single-tooth implants have been developed since, and attention has
      focused on the aesthetic component. This article presents a case study of single
      tooth implant prosthetics with the learning objective to enhance the knowledge of
      the single-tooth implant restorations.

PMID- 8148505
TI  - Practical stress absorption by means of modified abutments. Case presentations.
AB  - To improve the success rates of implants, numerous clinicians suggest progressive
      bone loading. The effectiveness of progressive loading can be enhanced by the use
      of stress-absorbing components. This paper reviews a polyoxymethylene intramobile
      element, which provides a resilient connection between the implant and prosthesis
      and reduces the stress transmitted to the implant and supporting bone, resulting
      in an improved long-term performance. This paper also introduces a relatively new
      intramobile connector system, which provides stress absorption and distributes
      the masticatory load in physiologic manner to the bone surrounding the implants.
      Types of bone and their locations in the mandible and the maxilla are discussed.
      Four case reports are used to illustrate the clinical procedure. The learning
      objective of this article is to expand the knowledge of available enhancements in
      stress absorption.

PMID- 8148506
TI  - Periodontitis and periimplantitis: one and the same?
AB  - Research shows that the same anaerobic, gram-negative pathogens are present in
      the periodontal and implant pocket or crevice. The implants in a partially
      edentulous case are probably more at risk due to the bacteria being more
      pathogenic and a seeding mechanism from the tooth pocket to the implant crevice.
      In the face of a normal microbial flora, retrograde periimplantitis or
      radiographic bone loss without gingival changes may be due to trauma because of
      overloading, loading too soon, and/or loading in a lateral direction. Finally,
      the combination of an infective process (periimplantitis) and noninfective or
      traumatic process (retrograde periimplantitis) will result in rapid osseous
      destruction and, possibly, loss of the implant fixture(s).

PMID- 8148507
TI  - Perfect dentistry? Only in a perfect world!

PMID- 8148508
TI  - Surgical criteria for endosseous implant placement: an overview.
AB  - This paper presents an overview of important criteria for successful endosseous
      implantation. It discusses implant-specific anatomy, preoperative planning, the
      influence of structure and quality of the available bone on implant prognosis,
      and the principles of mechanical implant site preparation. The presentation also
      considers the vitality of adjacent bone, implant surface integrity, local bone
      defect augmentation, implant selection, and immediate implantation. The learning
      objective of this article is to enhance the knowledge of surgical and implant
      site preparation protocol.

PMID- 8148509
TI  - Misapplication of the Tarasoff duty to driving cases: a call for a reframing of
      theory.
AB  - In the years since the original Tarasoff cases created a new duty for
      psychotherapists toward third parties harmed by patients' violence, a series of
      cases nationwide--so called "driving cases"--have applied Tarasoff-like reasoning
      to situations where a patient injured others while driving a car. Our thesis in
      this paper is that such application is inappropriate since it represents an
      unjustified and largely unexamined assumption that driving injury is an
      expression of the mental-illness-derived intended violence that justifies the
      Tarasoff duty and its inevitable associated breach of confidentiality. We suggest
      to the contrary that driving cases almost invariably result from a patient's
      negligent driving rather than intentional violence stemming from mental illness;
      that clinicians in most instances have almost no capacity, training, or clinical
      bases on which to predict a patient's future negligence, violence aside; and that
      the theory of driving cases should be revised.

PMID- 8148510
TI  - First year of Maryland's new CRP statute in one state hospital.
AB  - The first year of Maryland's new Clinical Review Panel (CRP) statute in one state
      psychiatric hospital is reviewed. CRPs provide a nonjudicial means to administer
      medication to an involuntarily committed psychiatric patient refusing medicines
      in a nonemergency situation. While the statute adds appropriate formal procedural
      protections and while the CRP process "works," the statute also adds the
      possibility of unnecessary legal proceedings. Clinical decisions about
      medications should be made by psychiatrists and not by lawyers or judges.

PMID- 8148511
TI  - The biases of child sexual abuse experts: believing is seeing.
AB  - Experts in clinical evaluations of child sexual abuse were studied using a
      paradigm that requested them to estimate the likelihood of a 3-year-old child
      having been sexually molested by her father, as alleged by her mother, when she
      was two years old. All of the experts claimed special qualifications and
      experience in the field of diagnosing and treating child sexual abuse victims.
      Expert-respondents provided two estimates of the likelihood that the child had
      been molested, the first following a detailed presentation of the clinical case
      by the actual evaluator of the child (the presentation included opportunities to
      ask questions ad libitum beyond the presentation material), the second following
      an extensive discussion of the clinical material with other child experts
      present. The range of estimated likelihoods that the child had been molested was
      extreme among the expert respondents. The clinical conference format that was
      used seemed to provide the experts with no apparent means for eliminating or
      reducing differences in their clinical opinions. Recommendations concerning how
      the supervising court should regulate further child-father contacts were
      similarly varied. The implications of these findings for judicial acceptance of
      expert testimony in cases of alleged child sexual abuse are discussed.

PMID- 8148512
TI  - Report of the task force on consent to voluntary hospitalization.

PMID- 8148513
TI  - Informed decision making in persons acquitted not guilty by reason of insanity.
AB  - Deciding to raise an insanity defense carries serious consequences. This is
      especially true for persons charged with minor offenses, for whom an acquittal
      not guilty by reason of insanity (NGRI) might lead to a longer period of
      incarceration than would conviction. Before raising an insanity defense, a
      defendant should be provided with information necessary to make an informed
      decision and should be competent to understand the consequences of the verdict.
      This study attempted, through retrospective review and concurrent evaluation, to
      determine the degree to which trial courts in Virginia attended to these
      important aspects of informed decision making before finding defendants charged
      with misdemeanors NGRI. The study also attempted to assess the degree to which
      defendants were competent and informed at the time of adjudication. In most
      instances, trial courts did not consider defendants' competence to make decisions
      regarding the insanity defense and did not consider whether defendants were
      informed about the consequences of a successful insanity defense at the time of
      adjudication. The average length of stay for these patients was (at least) 21
      months; most would have been released earlier had they been committed civilly
      rather than committed as a result of insanity pleas. We stress the need to
      educate judges, attorneys and forensic evaluators to the importance of
      considering defendants competence to plead insanity and of providing information
      about the consequences of a successful plea. We also propose that laws be changed
      to recognize the importance of these elements in the decision making process
      regarding pleas of insanity.

PMID- 8148514
TI  - Asbestos exposure and posttraumatic stress disorder.
AB  - In 48 cases of claims of psychic injury due to exposure to asbestos,
      posttraumatic stress disorder (PTSD) was alleged as a basis for damages in nine
      (19%). PTSD as currently defined refers to a specific syndrome following exposure
      to a life-threatening traumatic event, one outside the general range of people's
      experiences such as military combat, floods, earthquakes, bombing, torture, death
      camps--events either natural or man-made. The symptoms include reexperiencing of
      the event with intrusive thoughts or nightmares of the event, startle reactions,
      psychic numbing, and survival guilt. The application of this concept to chronic
      illness, often of minor degree, is quite inappropriate. The clinical data in the
      nine cases reveal no pertinent precipitating event and the lack of a clinical
      syndrome compatible with the disorder. The cases also generally reflect no
      psychiatric impairment, inadequate medical review, and lack of background history
      -common characteristics in asbestos litigation with no disabling pulmonary
      parenchymal impairment. If the results in this group are typical, then one must
      suspect the legitimacy of claims of psychic injury such as post-traumatic stress
      disorder from asbestos exposure and at the very least the reasonableness of the
      experts who provide input into the medicolegal process.

PMID- 8148515
TI  - Multiple personality disorder in criminal law.
AB  - The authors review the recent literature on multiple personality disorder (MPD),
      the most severe and chronic of the dissociative disorders, in relation to court
      cases of competence to stand trial, the insanity defense, and research on
      malingerers feigning MPD. Issues relevant in the assessment of competency and
      insanity are described. Features characteristic of MPD, including amnesia and
      alterations in consciousness and personality, have varying degrees of influence
      over the criminal behavior of an individual with MPD. As in other psychiatric
      disorders, the influence of MPD on an individual's competence to stand trial, and
      sanity, can be evaluated systematically. This article discusses a specific
      diagnostic tool, the Structured Clinical Interview for DSM-IV Dissociative
      Disorders (SCID-D), an extensively field tested instrument that is potentially
      quite useful in forensic assessment of suspects manifesting dissociative symptoms
      and disorders. The particular advantages of the SCID-D will be reviewed in the
      context of some well known criminal cases involving MPD. Further research using
      diagnostic interviews for the systematic assessment of dissociative symptoms and
      MPD in criminal cases will continue to clarify the influence of these symptoms in
      a forensic context.

PMID- 8148516
TI  - The noncustodial parent and medical treatment.
AB  - Despite the frequency of divorce, there are no comprehensive guidelines for the
      relative rights of custodial and noncustodial parents. Since there are no
      definite rules for the parties to follow, divorced parents receive conflicting
      advice and are more likely to engage in bitter misunderstandings. This paper
      creates a framework for defining whether the noncustodial parent has a right to
      authorize emergency medical care, routine medical care, serious nonemergency
      medical care, psychiatric evaluation, and psychiatric treatment. The author
      suggests that the noncustodial parent should be able to authorize routine medical
      treatment, but not routine psychiatric treatment.

PMID- 8148517
TI  - Pseudodementia and competency.
AB  - An increase in the number of challenges to competency determinations in probate
      cases parallels an increasingly aging population. In the literature on competency
      determination, there is little if any discussion of the implications of
      pseudodementing conditions, which can quite readily be misdiagnosed as true
      dementias, especially in the elderly. This case report describes a patient
      thought to have had a stroke with dementia and paresis who turned out to have had
      a pseudodementia. She later made a dramatic and somewhat surprising recovery. It
      subsequently came to light that a nearly successful attempt had been made to
      defraud her of her estate during her presumed dementia, which was thought to have
      been irreversible. The case underscores issues in competency determination,
      including matters of diagnosis, prognosis, and undue influence.

PMID- 8148518
TI  - An anatomic variation of the deltoid muscle (case report).
AB  - A bilateral anomaly of deltoid muscles was found in cadaver dissection of a
      middle aged male. Posterior part of the muscle was enclosed with a separate
      fascial sheath. There was no concomitant muscular anomaly in any part of the
      body.

PMID- 8148519
TI  - [The frondiformis ligament and stabilization of the posterior tarsus].
AB  - The frondiformis ligament is a part of the retinaculum extensorum of the instep.
      Actuated by the tendons of the extensor digitorum longus, it takes a direct
      effect on the talus and the calcaneum, induces the valgus of the tarsus and
      contributes to the stability of the ankle and the foot.

PMID- 8148520
TI  - [Anatomic bases of the surgical approach to the carpal tunnel. A propos of 50
      dissections].
AB  - After a classic dissection of 50 wrists in black african cadavers, we have
      studied carpal tunnel anatomy for therapeutic deductions. By a wide anterior
      incision following the longitudinal axis of the third finger remounting the
      inferior third of the forearm we studied both the anatomical limits specially the
      transcarpal ligament, the volare carpal ligament and also median nerve and
      flexores digitorum tendons. We have observed in 2 cases an ectopic second
      lumbrical muscle inside the carpal tunnel; we found numerous variations of the
      collateral and terminal branches of median nerve; we concluded that it is
      difficult to definitively establish the cartography of the terminal branches of
      median nerve. However our anatomical observations allowed us to choose larger and
      more medial surgical approach of the carpal tunnel to avoid the following
      complications: incomplete section of the carpal ligament, damages of collateral
      branches of median nerve, dislocation of flexor tendons of index and middle
      fingers, ignorance of anomalous muscle.

PMID- 8148521
TI  - [Arterial vascularization of the colon. The middle mesenteric artery].
AB  - In its modal disposition, the arterial vascularisation of the colon is on the
      dependence of the superior and inferior mesenteric arteries anastomosed by the
      way of "arcade de Riolan". Some more exceptional schemes can complicate this
      distribution: arteria colica media, medium mesenteric artery, intermesenteric
      arcus. This rare arterial dispositions can have a big practical importance, in
      the case of colic transposition, and more recently in the case of the utilization
      of the right gastroepiploic artery for coronary by-pass.

PMID- 8148522
TI  - [Aponeuroses and superficial fascia. Mechanical and structural properties].
AB  - Eleven superficial aponeuroses have been examined in order to study their
      biomechanical and structural properties. Specimens were taken from 5 fresh
      cadavers, 3 males, 2 females with a mean age between 40 and 60 years. The study
      was done by two methods: biomechanical and histological. Aponeuroses can be
      classified in 2 biomechanical and histological groups that match perfectly. The
      first group has biomechanical and histological properties similar to those of
      tendons, and the second group similar to those of tendons, and the second group
      similar to those of ligaments. Ignoring the biomechanical and histological
      properties of tendons, ligaments and aponeuroses can be the cause of failure of a
      number of ligament and tendon plasties. The surgeon has an important role in
      choosing the transplants according to the histological properties (thickness,
      length of structures, bundle orientation) and biomechanical properties (solidity
      and extensibility).

PMID- 8148523
TI  - Ligamentum teres hepatis: an unusual variation.
AB  - We report a variation of the ligamentum teres hepatis in 45 year old male
      cadaver. The ligamentum teres hepatis was found between the layers of the rectus
      sheath. A review of the literature reveals no additional reports of similar
      anomaly. There was also a variation in the form of the liver.

PMID- 8148524
TI  - [Usefulness of cytoprognostic classification combined with histoprognostic
      classification in breast cancer].
AB  - Histopathological grading according to Scarff Bloom Richardson can provide
      powerful prognostic information. However one criticism of this system is that 60%
      of patients cluster in grade 2 with no clear separation of good versus bad
      prognosis. In an effort to solve this problem we propose to add cytological
      grading performed on fine needle aspirates or imprints. Indeed histological grade
      2 (H2) group can be subdivided into 2 groups according to cytological grading:
      cytological grade 2 (C2) and grade 3 (C3). Analysis of cytometrical and
      proliferative features shows that H2 C3 tumors are closer from H3 C3 than from H2
      C2 tumors. So, using morphological evaluation, we propose to classify breast
      carcinoma into 2 groups: 1 group associating histological grade 1 tumors and
      histological grade 2, cytological grade 2 tumors; group 2, associating
      histological grade 3 tumors and histological grade 2, cytological grade 3 tumors.

PMID- 8148525
TI  - [Estimation of liver volume as a function of the individual's morphology].
AB  - Computed tomography using transversal scanning, may be usefull in the
      determination of liver volume. The aim of this study is to evaluate this
      technique in living subjects and to determine a relationship between liver volume
      and morphological body surface area and other morphological criteria. In a series
      of 25 patients, liver volume was computed from the body surface area, using a
      mathematical function. This method allow a quick and accurate determination of
      the liver volume which could be used in liver transplantation for a better
      matching between donor liver and recipient.

PMID- 8148526
TI  - Glutaraldehyde revisited.
AB  - January 1994 and the Control of Substances Hazardous to Health Regulations
      (COSHH) are being amended to include among others anaesthetic gases. For COSHH to
      be effective it has to be enforced. In order to see how this might be achieved
      one can perhaps look at the effectiveness of the Regulations since 1989.

PMID- 8148527
TI  - Methods of cleaning and disinfection.
AB  - Most equipment associated infection is due to inadequate cleaning and
      disinfection and not a failure in sterilisation practices. The method of
      disinfection chosen should depend on the risks associated with the procedure
      undertaken, the heat, pressure and chemical tolerances of the item and the time
      available for processing. Heat disinfection or sterilisation is preferred but if
      the item is heat sensitive, chemicals may have to be used. It is important that
      the process selected is effective against patient associated organisms and
      opportunistic pathogens present in the environment. The most effective stage of
      any decontamination procedure is thorough cleaning and this should accompany or
      precede all disinfection procedures. Automated processors offer the safest, most
      reliable option, providing they are suitably monitored and maintained and that
      staff wear appropriate protective clothing.

PMID- 8148528
TI  - Why nurses choose theatre nursing.
AB  - This qualitative study uses a grounded theory approach to explore the
      motivational factors which affect nurses' career choice, by focusing on the
      responses of post registration nurses undertaking a course in operating room
      nursing. In all, 15 nurses were interviewed. Examination of the data, using a
      constant comparative method, revealed five conceptual categories which were used
      to explain factors which affected their career decisions. The descriptive
      analysis of each section serves to illuminate individual motivational factors
      which brought these respondents into nursing and the initial socialization
      process: early experiences of theatre nursing; aspects of work which provide job
      satisfaction; how nurses use nursing skills in theatre and recruitment of future
      theatre nurses. For these respondents, theatre nursing provided a clear task
      identity which is seen as significant in terms of patient outcomes, it provides
      interesting and challenging work within a good team structure, which was viewed
      as important for job satisfaction and motivation.

PMID- 8148530
TI  - Reflections--at the cutting edge.

PMID- 8148529
TI  - The measurement of anaesthetic gases--legal requirement.

PMID- 8148531
TI  - MRSA in the operating department.
AB  - In recent years, infection control in the operating department has focused on the
      concept of universal precautions. This allows protection for both patients and
      staff in relation to blood borne pathogens. Recent research, however, suggests
      that the introduction of universal precautions could lead to an increase in the
      transmission of other pathogens, for example, Methicillin Resistant
      Staphylococcus Aureus (MRSA). This article aims to provide a brief overview of
      the universal precautions, followed by an in-depth consideration of MRSA, its
      history, incidence, transmission, effect and implications for both patients and
      staff in the operating department.

PMID- 8148532
TI  - Angioscopy management.

PMID- 8148533
TI  - Hip arthroscopy.
AB  - One of the more recent advances in keyhole surgery is hip arthroscopy. This
      particular area of arthroscopic surgery has been relatively neglected until
      recently but its development has widened the options open to the orthopaedic
      surgeon when considering the most appropriate treatment for the patient.
      Historically, attempts at hip arthroscopy were first reported in 1931 by Burman.
      Soon after, the procedure appears to have lost popularity until, during the mid
      1970s and 1980s, there appear isolated reports of hip arthroscopy.

PMID- 8148534
TI  - Caring, the essence of theatre nursing.

PMID- 8148535
TI  - Potential learning through critical incident analysis.

PMID- 8148536
TI  - An African diary.

PMID- 8148537
TI  - Ilizarov fixation.
AB  - Professor Gavanit Ilizarov, a Russian, was practising medicine in Siberia and
      although not trained as a surgeon he was becoming increasingly faced with
      orthopaedic problems. As he had no means of treating many of these, he devised
      his own system based on Kurstner wires and rings but using bicycle spokes and
      modified clutch rings. This was in 1951. He continued to make modifications over
      the years and, as the system has been introduced to the rest of the world,
      others, too, have added their own adaptations. There are now 42 components which
      go to make up the Ilizarov system. By using various combinations of these
      components it is possible to build a frame to treat a variety of orthopaedic
      problems i.e. deformities, non-unions and limb lengthening.

PMID- 8148538
TI  - Arthroscopic anterior cruciate ligament repair using patella tendon graft.

PMID- 8148539
TI  - Iliac crest bone donation--pain control.

PMID- 8148540
TI  - Techniques and results in bilateral sequential single lung transplantation. The
      National Heart & Lung Replacement Service.
AB  - Lung transplantation continues to evolve as a therapeutic option for patients
      with end-stage lung disease. Bilateral sequential single lung transplantation
      (BSSLTx) is a recent addition to the lung transplant surgeon's armamentarium that
      incorporates the benefits of single lung transplantation in patients who require
      double lung replacement while avoiding the morbidity inherent in the en bloc
      double lung transplant procedure. Between November 1992 and October 1993, 17
      recipients underwent 18 bilateral BSSLTx procedures for a variety of indications.
      In 53% of patients, the procedure was completed without the requirement for
      cardiopulmonary bypass. Telescoping of the bronchial anastomosis has proved
      satisfactory. Induction cytolytic therapy has not been utilized. Patients
      received methyl prednisolone from day 1 and as maintenance prednisolone therapy.
      Actuarial 1-year survival is 87%; 12 of the 15 survivors are in Functional Class
      I. BSSLTx is an evolving transplant option for patients who require double lung
      replacement. Definitive clinical diffusion of the procedure will depend upon
      intermediate and long-term outcomes for specific recipient pathologies.

PMID- 8148541
TI  - The safety of simultaneous arterial and coronary sinus perfusion: experimental
      background and initial clinical results.
AB  - Concern over myocardial damage from simultaneous arterial (antegrade) and
      coronary sinus (retrograde) perfusion has led to alternating between these
      delivery routes to maximize their individual benefits. Based upon predominant
      retrograde drainage via Thebesian veins, this study: (1) confirms experimentally
      the safety of simultaneous arterial and coronary sinus perfusion; and (2) reports
      initial clinical application of this combined strategy in 155 consecutive
      patients. EXPERIMENTAL: Five mini-pigs (25 to 30 kg) underwent 1 hour of aortic
      clamping with simultaneous aortic and coronary sinus perfusion at 200 mL/min with
      normal blood (37 degrees C) before and after 30 minutes of perfusion with either
      warm (37 degrees C) or cold (4 degrees C) blood cardioplegia. Coronary sinus
      pressure was always less than 30 mmHg. There was no right or left ventricular
      edema, lactate production, or lipid peroxidation as transmyocardial and
      myocardial conjugated dienes were unaltered, and postbypass recovered left
      ventricular end-systolic elastance (conductance catheter) and preload recruitable
      stroke work index 101% +/- 3% and 109% +/- 90%, respectively. CLINICAL:
      Simultaneous arterial/coronary sinus perfusion was used in 155 consecutive high
      risk patients (New York Heart Association Class III to IV) undergoing isolated
      coronary artery bypass grafting (CABG) (n = 109) and CABG+valve
      replacement/repair or aneurysm (n = 46). Included were 16 patients in cardiogenic
      shock and 24 undergoing reoperation. Mean aortic clamping time averaged 90 +/- 4
      minutes (range 30 to 207), with 3.5 +/- 0.1 grafts per patient; all anastomoses
      were performed with the aorta clamped. Cold intermittent blood cardioplegia was
      used for distal anastomoses and valve implantation/repair in 123 patients, and
      warm continuous blood cardioplegia was used in 32 patients. Following a warm
      cardioplegic reperfusate, all patients received warm noncardioplegic blood
      perfusion simultaneously via grafts and coronary sinus. Coronary sinus pressure
      was always less than 40 mmHg. Of 18 patients requiring postoperative mechanical
      circulatory support (IABP), 16 had IABP placed preoperatively for cardiogenic
      shock. There were three postoperative myocardial infarctions (2%), and six
      patients died (3.9% mortality). CONCLUSION: These experimental and clinical
      findings overcome perceived concerns about myocardial damage from simultaneous
      arterial and coronary sinus perfusion, and suggest this approach may add to the
      armamentarium of cardioprotective strategies.

PMID- 8148542
TI  - Aortic valve replacement with cryopreserved pulmonary allograft.
AB  - Experimental as well as clinical data support the finding of using the pulmonary
      valve as a systemic semilunar valve. From January 1990 to December 1992, 89
      patients received pulmonary cryopreserved allografts as aortic valve replacement.
      Sixteen subjects suffering from native or prosthetic valve endocarditis were
      included. Age ranged from 10 to 74 years. Sixty-five patients received isolated
      aortic valve replacement and 24 patients required additional surgical measures,
      such as coronary artery bypass graft, mitral valve reconstruction, replacement of
      the ascending aorta, supravalvular patch aortoplasty, ventricular septal defect
      closure, or myectomy. All operations were performed with normothermic bypass and
      cold cardioplegic arrest. Follow-up is maintained by visits to the outpatient
      clinic and echocardiographic assessment of the valve status every 3 months during
      the first year and every 6 months thereafter. There were four early and three
      late deaths. Four valves had to be removed: one intraoperatively and three 2, 4,
      and 24 months postoperatively. Echocardiographic assessment proved that gradients
      across the valve were low or absent. The majority of patients showed trivial or
      no aortic regurgitation during follow-up. No thromboembolic events have been
      observed and no new endocarditis occurred. Thus, event-free survival at 3 years
      is 87%. The results with pulmonary allografts have shown to be comparable to
      aortic allografts. Even in patients with acute native or prosthetic valve
      endocarditis, the use of cryopreserved pulmonary allografts has shown no adverse
      effects. We continue to implant cryopreserved pulmonary allografts in the aortic
      position. The long-term function of the valve, however, must be established,
      making continued evaluation of postoperative patients mandatory.

PMID- 8148543
TI  - Surgical management of Marfan syndrome in children.
AB  - Between August 1983 and January 1991, seven patients with Marfan syndrome
      underwent surgery for severe cardiovascular complications. The mean age at
      presentation was 5.7 months (range 4 to 9 months) in the infant group (n = 3),
      and 13.3 years (range 10 to 16 years) in a group of older children (n = 4). The
      primary indications for surgery in the infant group (performed at a mean of 3
      years after diagnosis) were ascending aortic aneurysm with valvar regurgitation
      in one patient, and severe mitral valve prolapse with regurgitation in two. In
      the older group, surgical indications (performed at a mean of 2.8 years after
      diagnosis) were ascending aortic aneurysm with valvar regurgitation in three
      patients and acute aortic dissection in one. For aortic surgery, a composite
      valved conduit was used in four patients, and an aortic homograft in one. For
      mitral valve surgery, mechanical prostheses were used. All patients survived the
      primary operation. Over a mean follow-up of 17.5 patient-years (range 1 to 9
      years), two patients in the infant Marfan group went on to further successful
      surgery (prosthetic mitral valve replacement and aortic root repair with aortic
      homograft) at a mean interval of 4.3 years after the initial surgery. Our results
      suggest that the major cardiovascular risk factors of Marfan syndrome in the
      young, even in those diagnosed during infancy, have been favorably changed by
      surgery with an encouraging medium-term outlook. The correct timing of surgery is
      aided by echocardiography.

PMID- 8148544
TI  - Management of mycotic aneurysm following repair of corrected transposition.
AB  - Omental flaps have been used for the treatment of infected aortic prosthetic
      grafts in adults. We report the case of a 26-month-old male who developed a
      mycotic aneurysm 9 months following insertion of a ventricle to pulmonary artery
      conduit. The aneurysm was excised and the reconstructed outflow tract wrapped
      with omentum. The patient has not had recurrence of his aneurysm following this
      course of management.

PMID- 8148545
TI  - Dissection of the atrial septum following mitral valve surgery.
AB  - Interlayer dissection of the atrial septum resulting in the formation of a cavity
      developed after an attempted repair of a mitral paraprosthetic leak. Subsequent
      rupture of the cavity into both atria resulted in a small left-to-right shunt and
      significant left ventriculoatrial regurgitation. Misplaced stitches, aimed at
      obliterating the paraprosthetic leak, were the cause of the dissection. This case
      illustrates a previously unreported complication of mitral valve surgery and
      stresses the importance of proper exposure and handling of the mitral annulus.

PMID- 8148546
TI  - Descending aortic dissection originating from a juxtaductal traumatic aneurysm:
      technical considerations.
AB  - A 65-year-old male presented with a descending aortic dissection. His past
      history was remarkable for severe blunt chest trauma 26 years prior to
      presentation. Operative and pathologic findings included a posttraumatic
      pseudoaneurysm of the thoracic aorta and an aortic dissection that originated
      from the orifice of the pseudoaneurysm. The ductal fovea, the mouth of the
      pseudoaneurysm, is an area that may be more susceptible to accelerated
      atherosclerosis and the complications of atherosclerosis including aortic
      dissection.

PMID- 8148547
TI  - Donor/recipient aorta size mismatch in heart transplantation: a technical
      alternative.
AB  - A technical alternative is proposed to enable transplantation in cases of
      considerable size mismatch between donor and recipient aorta: interposition of a
      Dacron graft of intermediate diameter. This procedure was performed in a 56-year
      old patient weighing 75 kg in whom a heart from a 40-kg donor was implanted.

PMID- 8148548
TI  - Simpler locally focused tomography in MR imaging.
AB  - The author describes a simple technique for performing locally focused tomography
      with magnetic resonance imaging. In contrast to a previous technique, which
      utilized wave functions to represent k-space data, the one described here does
      not require complicated experimental design and reconstruction procedures and is
      easy to implement and understand. The technique is verified with an experimental
      study. Technical details and experimental results are presented.

PMID- 8148549
TI  - Angle-dependent utilization of gradient hardware for oblique MR imaging.
AB  - A straightforward method for calculating maximum gradient amplitudes for the
      frequency-encoding, phase-encoding, and section-select functions in oblique
      magnetic resonance (MR) imaging is presented. The calculated amplitude values
      depend on the prescribed angulation and on which of the three functions are
      simultaneously active. The derived expressions are optimal in most cases, and
      when not optimal, they still offer substantial improvement over calculations that
      do not incorporate angular information. Both matrix-based and geometric
      interpretations are presented.

PMID- 8148550
TI  - MR imaging of disorders of the brachial plexus.
AB  - The authors evaluated 64 consecutive patients with suspected brachial plexus (BP)
      abnormalities of diverse cause with magnetic resonance (MR) imaging, using the
      body coil and a standardized protocol. Of the 43 patients for whom follow-up was
      available, 25 were suspected of having neoplastic involvement of the BP, nine had
      sustained injuries, and nine presented with BP symptoms of uncertain cause. MR
      imaging was 63% sensitive, 100% specific, and 77% accurate in demonstrating the
      abnormality in this diverse patient population. When patients with neoplastic and
      traumatic disorders were considered separately, sensitivity increased to 81%,
      accuracy to 88%, and specificity remained unchanged. In the patients with a
      clinical diagnosis of idiopathic or viral plexitis, the MR imaging findings were
      normal, serving to exclude other structural abnormalities. It is concluded that
      MR imaging is valuable in the assessment of a wide range of BP disorders.

PMID- 8148551
TI  - MR imaging findings after transplant surgery for Parkinson disease.
AB  - The authors describe the magnetic resonance (MR) imaging appearance of the head
      of the right caudate nucleus in patients who have undergone adrenal medullary
      transplant surgery for Parkinson disease. All four patients examined showed some
      clinical improvement after surgery. The MR images acquired 4-6 months
      postoperatively showed no evidence of caudate atrophy. Three of the four patients
      showed some increase in size of the operated caudate head relative to
      preoperative studies. Neither cavitation nor high signal intensity on T2-weighted
      images was evident within the caudate head. The one patient studied after
      administration of gadopentetate dimeglumine showed no abnormal enhancement. These
      images provided a description of the transplant site and also suggested that the
      clinical improvement seen was not due to simple ablation of caudate tissue or to
      postoperative inflammation. The increase in size of the caudate head also
      suggested that some implanted tissue may have remained in these patients at the
      time the MR images were acquired.

PMID- 8148552
TI  - Velocity and flow quantitation in the superior sagittal sinus with ungated and
      cine (gated) phase-contrast MR imaging.
AB  - Normal blood flow and velocity in the superior sagittal sinus were measured in 30
      patients. A fast two-dimensional ungated phase-contrast (PC) pulse sequence was
      compared with a peripherally gated cine PC technique for velocity and flow
      quantitation. The same imaging parameters were used for both methods. Measured
      values for mean velocity and flow obtained with the two methods were compared by
      using regression analysis and t testing. For blood flow, the correlation
      coefficient was .976. For velocity measurements, r was .950. Mean flow was 285
      mL/min +/- 19 with the ungated PC method and 281 mL/min +/- 19 with the cine PC
      method. The mean velocities measured with the two methods were 12.94 cm/sec +/-
      1.1 and 13.59 cm/sec +/- 1.1, respectively. There was no significant difference
      (paired t test) between the methods for mean flow or velocity data. This was true
      even though flow in the superior sagittal sinus is moderately pulsatile, as shown
      with the cine PC technique. The ungated PC method provided these data in 13
      seconds versus 3.5 minutes for the cine PC method.

PMID- 8148553
TI  - MR angiography of congenital heart disease: value of segmented two-dimensional
      inflow technique and maximum-intensity-projection display.
AB  - Magnetic resonance (MR) angiography of the cardiovascular system was evaluated in
      41 patients with congenital heart disease by using a two-dimensional (2D) inflow
      technique based on a magnetization-prepared gradient-echo pulse sequence with
      segmented k-space data acquisition and electrocardiographic gating at 0.5 T.
      Inversion and saturation prepulses were used to suppress stationary tissue and
      enhance intravascular signal. Presaturation slabs were applied where certain
      vascular structures had to be suppressed. Sequence parameters were optimized by
      evaluating signal intensity and contrast characteristics for various flip angles
      and inversion and saturation delay times. The heart and intrathoracic vasculature
      were encompassed with 40-50 overlapping sections. Both 2D angiograms and maximum
      intensity-projection images were evaluated. Combining data sets acquired in the
      sagittal and transverse orientations provided the most satisfactory information
      about the pulmonary arteries. The highest signal-to-noise ratios were obtained
      with a flip angle of 65 degrees and short prepulse delay times. Two-dimensional
      MR angiography can provide useful diagnostic information but requires a thorough
      understanding of in-plane and hemodynamically induced signal intensity changes.

PMID- 8148554
TI  - Carotid and vertebral artery blood flow in left- and right-handed healthy
      subjects measured with MR velocity mapping.
AB  - The goal of the study was to establish normal carotid artery flow rates in left
      handed and right-handed individuals as a standard against which patients with
      carotid artery disease could be compared. Antegrade and retrograde flow were
      measured in the ascending aorta, in the right and left common, internal, and
      external carotid arteries, and in the vertebral arteries of 12 healthy subjects.
      Five subjects were right-handed, five left-handed, and two ambidextrous. Measured
      flow rates were as follows: common carotid arteries, 360-557 mL/min (mean [+/-
      standard deviation], 465 mL/min +/- 52); internal carotid arteries, 132-367
      mL/min (mean, 265 mL/min +/- 60); external carotid arteries, 113-309 mL/min
      (mean, 186 mL/min +/- 51); vertebral arteries from 133-308 mL/min (mean, 244
      mL/min +/- 43); and cerebral circulation, 546-931 mL/min (mean, 774 mL/min +/-
      134). All right-handed subjects had higher flow rates in the left internal
      carotid artery than in the right, and all left-handed subjects had higher flow
      rates in the right internal carotid artery (P = .007). There were no significant
      differences in left and right common carotid artery flow rates between left- and
      right-handed subjects. The standard deviation of a single measurement was 5%. The
      flow rates were similar to those obtained previously with other techniques and
      could be used as a normal standard.

PMID- 8148555
TI  - Techniques for high-resolution MR imaging of atherosclerotic plaque.
AB  - Atherosclerotic cardiovascular disease is the most common cause of death in the
      United States. Investigation of atherosclerotic plaque morphology and composition
      is important because the findings may be useful in predicting prognosis or
      response to therapy. This study presents high-resolution magnetic resonance (MR)
      imaging techniques developed on a 1.5-T whole-body imager with a custom-built
      surface coil, for characterizing the composition and morphology of plaque removed
      at carotid endarterectomy. The initial comparison of MR imaging and histologic
      results showed good correlation. In conjunction with MR angiography, these
      techniques could be used in in vivo imaging to define the size, location, and
      contents of atherosclerotic plaque at the carotid bifurcation.

PMID- 8148556
TI  - Measurement of stroke volume and cardiac output within a single breath hold with
      echo-planar MR imaging.
AB  - The measurement of cardiac output and ejection fraction is useful in the
      treatment of diverse cardiac and cardiopulmonary disease states. Although several
      techniques are available for accurate measurement of left ventricular parameters,
      assessment of the right ventricle is less well represented. No single method is
      overwhelmingly superior, each having different strengths and weaknesses. In the
      present study, the applicability of an echo-planar magnetic resonance (MR)
      imaging method in which a complete volumetric measurement of the right and left
      ventricles may be obtained during 12 heart-beats is demonstrated. This rapidity
      permits imaging during a 15-second breath hold. The authors show in 12 volunteers
      that breath-hold echo-planar volume measurements of both ventricles were
      consistent with results obtained with conventional MR imaging methods.

PMID- 8148558
TI  - Tissue temperature monitoring for thermal interventional therapy: comparison of
      T1-weighted MR sequences.
AB  - For thermal interventional therapy, near real-time monitoring of temperature
      changes in the treated area is desirable. In this study, various fast T1-weighted
      magnetic resonance (MR) imaging protocols were compared to determine the
      sensitivity and resolution of signal intensity for temperatures within the range
      of 36 degrees C-66 degrees C in gel phantoms and in vitro porcine liver
      specimens. The results showed that a T1-weighted fast spin-echo sequence with a
      TR of 100 msec had better temperature sensitivity and resolution than other
      sequences with comparable temporal resolutions. The longer imaging times required
      for fast spin-echo sequences with a TR of 300 msec did not improve temperature
      sensitivity. The methods introduced to evaluate temperature sensitivity and
      resolution should prove useful in selecting appropriate MR protocols for
      monitoring thermal treatment modalities such as interstitial laser therapy,
      focused ultrasound therapy, or radio-frequency heating.

PMID- 8148557
TI  - Quantitative MR relaxometry study of muscle composition and function in Duchenne
      muscular dystrophy.
AB  - Magnetic resonance imaging and maps of T1 and T2 values were used to study muscle
      composition in Duchenne muscular dystrophy (DMD). The mean T2 of anterior tibial
      muscle was 27 msec in healthy control subjects and 43 msec with increased fatty
      infiltration in DMD patients. In stronger DMD patients, the distribution of
      muscle T2 values was narrow, centered at 27 msec as in the controls, with a
      nonoverlapping fat peak centered at 49 msec. In weaker DMD patients, the width of
      the muscle T2 peak increased and the peak shifted toward the fat peak. Mean
      muscle T1 decreased from 1.7 to 0.6 second with increasing fatty infiltration.
      These results show that quantitative T1 and T2 maps may be used to assess muscle
      status and monitor DMD progression.

PMID- 8148559
TI  - Effect of MR imaging on the normal human pineal body: measurement of plasma
      melatonin levels.
AB  - Production of melatonin, a hormone synthesized and secreted by the pineal body,
      has been suppressed by electromagnetic fields in some but not all animal studies.
      Magnetic resonance (MR) imaging at 1.5 T was evaluated for its ability to
      modulate the level of melatonin in eight male volunteers. Subjects were exposed
      to three conditions, respectively, between 1:00 and 2:00 AM on different nights:
      (a) a series of routine MR pulse sequences for brain imaging in dark conditions,
      (b) dark control conditions, and (c) bright-light control conditions. Plasma was
      analyzed for melatonin and cortisol levels. Hormonal changes were analyzed by one
      factor repeated measures within-subject analysis of variance. These conditions
      were associated with significant differences in melatonin levels: F(2, 6) = 7.95,
      and P = .021. Subjects exposed to darkness showed a typical increase in melatonin
      concentration. Subjects exposed to bright light showed a characteristic
      suppression of melatonin concentration. Those exposed to the MR imaging fields
      showed an increase in melatonin level similar to that seen in the dark control
      condition. Light and MR imaging had no significant effects on cortisol levels.
      Thus, MR imaging at field strengths known to modulate melatonin levels in rats
      did not suppress melatonin production in human subjects.

PMID- 8148560
TI  - Hematopoietic reconstitution after bone marrow transplantation: assessment with
      MR imaging and H-1 localized spectroscopy.
AB  - Magnetic resonance (MR) studies were performed in 14 patients as early as
      possible (21-110 days) after bone marrow transplantation (BMT). MR
      characteristics of lumbar vertebral bone marrow were studied with T1-weighted
      spin-echo imaging, water- and fat-selective imaging with a frequency-selective
      excitation technique, and point-resolved spatially localized proton spectroscopy.
      Signals from water and fat protons and their T1 and T2 values were analyzed.
      Water proton signal intensity correlated well with cellularity within bone
      marrow, as determined with parallel iliac crest biopsies. The fraction of signal
      from water in red bone marrow of patients with allogeneic transplants from
      siblings (four cases) was significantly higher than in four patients with
      autologous transplants. The latter showed very low cellularity in the period of
      about 4 weeks after BMT because of the cytotoxic pretreatment of the bone marrow.
      The MR results in six patients with allogeneic transplants from unrelated donors
      ranged widely, depending on the complications after BMT. Analysis of data
      obtained with the different techniques showed that water- and fat-selective MR
      imaging and spectroscopic methods are useful for noninvasive monitoring of
      hematopoietic reconstitution after BMT.

PMID- 8148561
TI  - Magnetization transfer imaging with pulsed off-resonance saturation: variation in
      contrast with saturation duty cycle.
AB  - Magnetization transfer contrast (MTC) can be generated in magnetic resonance
      images of water-containing macromolecular structures. Results obtained with the
      pulsed off-resonance saturation technique for achieving MTC are presented,
      allowing comparison of this technique with others. The magnetization transfer
      effect is demonstrated in newborn piglet brain and bovine muscle tissue, as well
      as in human subjects. MTC increases nonlinearly with the duty cycle of the off
      resonance irradiation, approaching a maximum value corresponding to continuous
      irradiation. However, approximately half of the available contrast can be
      obtained at a given saturation offset frequency, with 16% irradiation duty cycle.
      Examples of MTC in various human tissues demonstrate the specificity of this
      technique at power levels within U.S. Food and Drug Administration guidelines.
      Plots of MTC versus the irradiation offset frequency demonstrate the effects of
      magnetization transfer and are compared with the curve generated by a control
      phantom that does not show magnetization transfer. Magnetization transfer imaging
      with pulsed off-resonance saturation is effective and easily implemented and may
      be useful in the investigation of saturation transfer phenomena in tissue.

PMID- 8148563
TI  - Improved T1-weighted two-dimensional MP-GRE imaging of the liver with variable
      flip angles for shaping the signal evolution.
AB  - The recently introduced method of shaping the transient signal evolution in
      magnetization-prepared gradient-echo (MP-GRE) imaging with variable flip angles
      has been applied to two-dimensional (2D) MP-GRE imaging of the abdomen. The
      technique was analyzed by using theoretical models and was implemented on a
      standard 1.5-T whole-body imager with a segmented acquisition. Theoretical models
      predicted that the variable-flip-angle 2D MP-GRE sequence would increase liver
      spleen signal difference--to-noise ratios by 290%, 110%, and 160% compared with a
      2D MP-GRE sequence with a flip angle of 10 degrees and sequential phase encoding,
      a 2D MP-GRE sequence with a flip angle of 30 degrees and centric phase encoding,
      and the fast low-angle shot sequence, respectively. Experimental measurements
      supported the theoretical predictions.

PMID- 8148562
TI  - Spin-echo and dynamic gadolinium-enhanced FLASH MR imaging of hepatocellular
      carcinoma: correlation with histopathologic findings.
AB  - Evaluation of histologic subtype and degree of differentiation in hepatocellular
      carcinoma (HCC) is essential because it affects patient prognosis and treatment
      planning. To evaluate the histologic subtype of HCC with magnetic resonance (MR)
      imaging, conventional spin-echo and dynamic studies were correlated with
      histopathologic and angiographic findings in 72 HCCs. Dynamic MR imaging was
      performed with the fast low-angle shot (FLASH) technique after administration of
      gadopentetate dimeglumine. There was considerable overlap in signal intensity
      between various tumor grades on both T1- and T2-weighted images. On dynamic MR
      images, the peak contrast enhancement ratio correlated with tumor grade (well
      differentiated, 29.5 +/- 24.7; moderately differentiated, 63.5 +/- 24.1; poorly
      differentiated, 86.9 +/- 26.4) or degree of dilatation of the sinusoidlike
      vascular space between tumor cells. The maximum contrast-to-noise ratio in tumor
      (relative to surrounding liver) was achieved within 60 seconds in 45 HCCs (mostly
      of the trabecular or pseudoglandular type). Enhancement was slight or minimal in
      17 tumors (mostly small, well-differentiated tumors). In 10 tumors, the degree of
      enhancement increased with time, with maximum enhancement in the delayed phase
      (most frequently in scirrhous HCC). These dynamic patterns correlated with
      angiographic findings. These data indicate that the degree and pattern of
      enhancement on dynamic MR images reflect tumor differentiation and architecture
      of HCC.

PMID- 8148564
TI  - Recurrent biliary cystadenoma: MR imaging appearance.
AB  - The authors report the case of a 37-year-old woman with a biliary cystadenoma
      that mimicked a liver cyst. The magnetic resonance (MR) imaging features of this
      rare lesion were correlated with the pathologic findings, showing the potential
      of MR imaging for depicting and aiding in the diagnosis of biliary cystadenoma
      and its recurrence.

PMID- 8148565
TI  - Spine fracture risk is predicted by non-spine fractures.
AB  - A prospective cohort study of 1098 postmenopausal Japanese-American women
      evaluated the relationship between baseline non-spine fractures and new
      (incident) spine fractures. At the baseline examination in 1981, prevalent non
      spine fractures were ascertained by interview, and prevalent spine fractures by
      radiograph. Bone mass measurements of the distal radius, proximal radius,
      calcaneus (1981), the lumbar spine (1984) were obtained and repeated at 1- to 2
      year intervals. Women with existing non-spine fractures have a threefold greater
      risk of subsequent spine fractures, independent of bone mass, and independent of
      the known association between prevalent spine fractures and subsequent spine
      fractures. Women with both a prevalent non-spine fracture and low bone mass (50th
      percentile or lower) have an eightfold greater risk of new spine fractures
      compared with women above the 50th percentile of bone mass and no prevalent
      fractures. In addition to low bone mass, both prevalent spine fractures and
      prevalent non-spine fractures are strong risk factors for subsequent spine
      fracture. These data suggest that not all osteoporotic risk factors are expressed
      via bone mass, and that other, unmeasured risk factors, such as bone quality
      defects, may explain these results. In clinical terms, women with both prevalent
      fractures and low bone mass should be recognized as being at extremely high risk,
      and treatment potency should be commensurate with this level of risk.

PMID- 8148566
TI  - Patient dose in dual x-ray absorptiometry.
AB  - Dual x-ray absorptiometry (DXA) provides a convenient, non-invasive method of
      assessing skeletal bone mineral which is widely used for clinical studies. This
      report describes a study to estimate the effective dose of radiation (ICRP-60
      (1990)) to a typical female patient from scans performed on three DXA scanners:
      the Hologic QDR-1000, QDR-1000/W and QDR-2000. The scans modes studied were:
      total body; anteroposterior (AP) lumbar spine; lateral lumbar spine; proximal
      femur; distal forearm. An ionization chamber and tissue-equivalent phantom were
      used to determine entrance surface dose and percentage depth-dose curves for each
      scan mode. Anatomical data from ICRP-23 (Reference Man) and a body section atlas
      were used to estimate the absorbed dose to each organ in the scan fields.
      Effective dose was estimated using the ICRP-60 tissue weighting factors and the
      fraction of each organ in the scan field. Results are summarized below. Figures
      for the effective dose are given both excluding and (in brackets) including the
      ovaries to cover the cases of postmenopausal and premenopausal women
      respectively.

PMID- 8148567
TI  - Determinants of hormone replacement therapy among postmenopausal women enrolled
      in the French GAZEL cohort.
AB  - Although the efficacy of hormonal replacement therapy (HRT) regarding numerous
      consequences of menopause is proven, its prevalence of use is low, as is
      compliance with the prescribed treatment. The aim of this work was to study the
      factors influencing a woman's decision to take HRT by analyzing the determinants
      of HRT use of at least 6 months' duration among post-menopausal women working for
      a French company and enrolled in a cohort study. Special attention was paid to
      the women's expectations of HRT. We compared two groups of women: 113 current HRT
      users who had been users for at least 6 months and 101 never users. Among the 113
      current users, the most frequent treatment was a combination of oestrogen and
      progestin (86%). The determinants of HRT use for at least 6 months included a
      prior spinal radiograph, which showed a significant relationship with the use of
      hormone treatment (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.2-4.7), a
      current marriage (OR 2.5; 95% CI 1.3-5.1) and previous hot flushes (OR 2.4; 95%
      CI 1.2-4.9). The strongest determinant was an expectation that HRT would prevent
      osteoporosis (OR 5.0; 95% CI 2.2-11.6). In this population concern about
      osteoporosis appears to be an important determinant of HRT use. Our results
      underline the importance of the diffusion of information among physicians and
      women about HRT's benefits, especially its efficacy in preventing osteoporosis.

PMID- 8148568
TI  - In vitro study of osteoblastic cells from patients with idiopathic osteoporosis
      and comparison with cells from non-osteoporotic controls.
AB  - We have examined bone cells derived from iliac crest trabecular explants of 30
      patients with idiopathic osteoporosis and 45 control subjects in order to
      determine whether intrinsic abnormalities in osteoblast function may contribute
      to the decreased bone formation observed in this disease. Bone cells isolated
      from all subjects expressed several in vitro characteristics of the osteoblast
      phenotype including adenylate cyclase responsiveness to parathyroid hormone (PTH)
      and prostaglandin E1 (PGE1), basal and 1,25(OH)2D3-stimulated alkaline
      phosphatase activity and osteocalcin production. Results were compared amongst
      three subject groups; young controls less than 40 years old, older controls over
      40 years old, and osteoporotics. Osteoporotic cells were found in general to be
      fully active in vitro. There were no differences between osteoporotic and control
      cells in their basal levels of adenylate cyclase, or alkaline phosphatase, in
      their growth rates, or cell morphology. The cyclic AMP (cAMP) response to PTH was
      significantly lower in osteoporotic cells (71%, p < 0.01) and older control cells
      (64%, p < 0.005) relative to the response in cells from younger controls,
      suggesting that the decreased responsiveness in osteoporotic cells was due to
      subject age rather than the osteoporotic state. At the same time, the cAMP
      responses to PGE1 and cholera toxin were similar in cells from all three subject
      groups. The response to forskolin was reduced to about 40% in osteoporotic cells
      compared with controls, but this was not mirrored by similar differences in the
      responses to PTH, PGE1 or cholera toxin, suggesting that the availability of
      catalytic subunits is not rate-limiting in these cells. 1,25(OH)2D3-stimulated
      osteocalcin production was 220% higher in osteoporotics than in older controls,
      but the numbers tested were small and the difference did not reach significance.
      The one significant abnormality we observed in osteoporotic cells was in alkaline
      phosphatase activity: 1,25(OH)2D3-stimulated alkaline phosphatase activity was
      twofold higher in osteoporotics than in younger (p < 0.05), older (p < 0.05) and
      pooled controls (p < 0.025). The significance of this finding is unknown, but we
      postulate that it may reflect an intrinsic abnormality in osteoblast function in
      patients with idiopathic osteoporosis.

PMID- 8148569
TI  - Skin thickness does not reflect bone mineral density in postmenopausal women.
AB  - Skin and bone both contain primarily type I collagen in connective tissue
      matrices and are assumed to be related due to this common organic constituent.
      The purpose of this study was to investigate whether skin thickness measurements
      by ultrasound (US) could be used for screening for low bone mass. In 94 healthy,
      white, non-smoking women, 1-3 years postmenopause, the thickness of the skin of
      the left upper arm and forearm was measured by ultrasound (US). These
      measurements were compared with values of bone mineral density (BMD) as measured
      by quantitative computed tomography (QCT) of the lumbar spine and quantitative
      video micro-densitometry (QMD) of the hand. The correlation found between US skin
      thickness measurements and BMD results was of low magnitude and not significant.
      It is concluded that US measurements of skin thickness cannot be used to screen
      early postmenopausal women for low bone mass.

PMID- 8148570
TI  - Non-responders to hormone replacement therapy for the prevention of
      postmenopausal bone loss: do they exist?
AB  - Hormone replacement therapy (HRT) prevents postmenopausal bone loss, but the
      prevalence of non-responders in healthy early postmenopausal women is not known.
      In order to study this, we reviewed data from three published studies, each
      carried out in a randomized, placebo-controlled, longitudinal design over 2 year,
      that used seven hormone replacement therapies. Bone mineral content (BMC) was
      measured in the distal forearm by single photon absorptiometry. A mathematical
      model for elimination of measurement errors was applied to published BMC data.
      After this correction, we found that only 1.2% of early healthy postmenopausal
      women who are receiving HRT in conventional doses will lose more than 1% of
      forearm BMC per year. In conclusion, most, if not all, healthy early
      postmenopausal women who might need HRT against loss of bone will respond
      positively in forearm BMC to such therapy.

PMID- 8148571
TI  - Quantitative ultrasound of the heel: correlation with densitometric measurements
      at different skeletal sites.
AB  - To assess the utility of quantitative ultrasound (QUS) of the heel for
      osteoporosis screening, we studied a group of 170 early postmenopausal women
      using both QUS of the heel and dual-energy X-ray absorptiometry (DXA) at the
      spine, hip, forearm, and whole body. On the basis of the linear regression
      results between QUS and DXA, a 95% bone mineral density (BMD) estimate confidence
      range was defined. Correlation coefficients between the QUS measurements and DXA
      ranged from 0.26 to 0.63. The confidence ranges for the estimated BMD based on a
      QUS measurement of the heel were large, such that an estimation of skeletal BMD
      at any of the DXA sites measured was not possible. For example, an estimate of
      the normative anteroposterior spine BMD (i.e. the T-score or the Z-score) based
      on a calcaneal ultrasound reading would have an error of +/- 1.9 standard
      deviations. Results for predicting the normative BMD of the other DXA regions
      were similar, with expected errors ranging from +/- 1.4 to +/- 2.0 standard
      deviations. We therefore conclude that QUS is not suited for the screening of
      early postmenopausal women for low axial or peripheral BMD. However, QUS may have
      a role as an independent predictor of fracture by measuring skeletal properties
      in addition to bone density.

PMID- 8148572
TI  - Bone density of the calcaneus and fractures in 75- and 80-year-old men and women.
AB  - Bone mineral density of the calcaneus in relation to fractures was studied both
      retrospectively and prospectively among the 75- and 80-year-old men and women
      resident in the city of Jyvaskyla, Finland, in 1989 and 1990, respectively. The
      bone measurements were performed at the calcaneus by 125I-photon absorption.
      Retrospective fracture (RF) history after age 50 was collected by questionnaire
      and interview, and reported fractures were checked from medical records. In the
      retrospective study, in the 75-year-olds a fracture was found in 22% (n = 22) of
      men and in 45% (n = 84) of women. The corresponding figures for the 80-year-olds
      were 16% (n = 9) and 35% (n = 48). Over half of the fractures were of the
      wrist/hand or ankle/leg. Prospective fractures (PF) were recorded over periods of
      29-34 months. Twenty of the 75-year-olds and 16 of the 80-year-olds sustained a
      fracture during the follow-up period. In the 75-year-olds, the results showed
      that both RF and PF women, together with the RF men, had lower bone area density
      (BMDa) and volume density (BMDv) than the non-fracture (NF) subjects (p = 0.001
      0.011). In the 80-year-olds, significantly lower BMDa was found in the RF women
      (p = 0.008) and lower BMDv in the PF women (p = 0.024) compared with the NF
      subjects. During the follow-up period there were no fractures in either of the
      sex or age groups among those with BMDa and BMDv values greater than 1 SD above
      the mean. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148573
TI  - Kyphosis in older women and its relation to back pain, disability and osteopenia:
      the study of osteoporotic fractures.
AB  - To test the hypothesis that thoracic kyphosis is associated with substantial
      pain, disability, and height loss, we measured thoracic curvature, using an
      architect's flexicurve, of 610 women aged 65-91 years who were recruited from
      population-based listings. We assessed study subjects for back pain, back-related
      disability, height loss since age 25 years, perceived state of health, and bone
      mineral density (BMD) at the spine, calcaneus, proximal radius, and distal
      radius. Compared with the rest of the cohort, the 10% of women with the most
      severe kyphosis had 7%-17% lower BMD (p < 0.001) and had lost an additional 2.4
      cm height (p < 0.001). However, kyphotic women had no greater back pain,
      disability caused by back problems, or poorer health. This cross-sectional study
      suggests that kyphosis is associated with decreased BMD and loss of height but
      does not cause substantial chronic back pain, disability, or poor health in older
      women.

PMID- 8148575
TI  - Role of cytokines in bronchial hyperresponsiveness.

PMID- 8148574
TI  - The incidence of hip fractures in independent and institutionalized elderly
      people.
AB  - The incidence density of hip fractures in the population of Amsterdam, aged 70
      years and over, was studied according to the type of residence. In 1989, 655
      patients were admitted to nine hospitals within Amsterdam for a hip fracture.
      Postal codes were used to classify the residence of the population and the hip
      fracture cases as independent, home for the elderly or nursing home. Stepwise
      logistic regression was used for data analysis. The risk of hip fracture
      increased with age and was 1.7 times higher for women than for men. In the age
      group 70-74 years the relative risk (RR) was 7.6 for those in homes for the
      elderly and 5.8 for those in nursing homes, when compared with the independent
      elderly. This RR was approximately 1 for those in homes for the elderly aged 85
      years and over. However, in nursing homes the RR was still 2.8 in the age group
      95+. We concluded that, despite protective measures against falls, the
      institutionalized elderly are at greater risk of hip fracture than the
      independent elderly of the same age and sex. This higher risk is especially
      apparent in the 'younger' age groups.

PMID- 8148576
TI  - Potential species dependency for the pulmonary antiallergic effects of
      aerosolized heparin.
AB  - The inhibition of antigen aerosol-induced bronchoconstriction by heparin aerosol
      pretreatment has been demonstrated in conscious sheep. Therefore, we investigated
      the effect of heparin aerosol pretreatment on antigen aerosol-induced
      bronchoconstriction in anaesthetized and ventilated guinea-pigs. In one study all
      animals were pretreated with propranolol and indomethacin in order to produce a
      large bronchoconstriction, whereas in a second study this pretreatment was
      omitted in order to produce a smaller bronchoconstriction. In both studies
      aerosolized heparin failed to inhibit antigen aerosol-induced
      bronchoconstriction, whether delivered at 1, 10 and 100 mg/ml 10 min prior to
      antigen challenge or delivered at 50 mg/ml 60 min prior to antigen challenge. In
      contrast, salbutamol aerosol pretreatment (1 mg/ml, delivered 10 min prior to
      antigen challenge) produced a near-maximum inhibition of antigen aerosol-induced
      bronchoconstriction. These results suggest that the pulmonary antiallergic
      effects of aerosolized heparin are potentially species dependent.

PMID- 8148577
TI  - The effect of sodium transport and calcium channel inhibitors on phorbol ester
      induced contraction of bovine airway smooth muscle.
AB  - We studied the role of sodium transport and calcium channels in protein kinase C
      mediated signal-transduction pathways in bovine airway smooth muscle. 4-beta
      phorbol 12,13 dibutyrate (PDB), an activator of protein kinase C, caused dose
      related slowly developing contraction in bovine bronchial rings with a peak
      effect at 60-90 min. 4-alpha PDB, an inactive analogue, was without effect. Mean
      peak PDB-induced contraction (measured as a percentage of the maximum response to
      methacholine) was reduced from 122% to 20% when experiments were carried out in
      calcium-free fluids +EDTA (10(-3) M). Similar reductions were seen in the
      presence of nifedipine and verapamil, inhibitors of voltage-dependent calcium
      channels. Amiloride at high concentrations (10(-3) M) reduced the contractile
      response to PDB from 87% to 20%, but at a concentration which inhibits the sodium
      entry channel (10(-6) M), amiloride was without effect. 5-N,N-hexamethylene
      amiloride (10(-5) M), a specific inhibitor of Na+/H+ exchange, did not alter the
      contraction produced by PDB. Frusemide (10(-5) M), an inhibitor of Na(+)-K(+)-Cl-
      cotransport, was without effect on PDB contractions. We conclude that phorbol
      ester-induced contraction of bovine airway smooth muscle is dependent on calcium
      entry via voltage-dependent calcium channels but is independent of Na+ entry,
      Na+/H+ exchange or Na(+)-K(+)-Cl- cotransport.

PMID- 8148578
TI  - Inhibitory effect of a thromboxane A2 synthetase inhibitor OKY-046 on bronchial
      hyperresponsiveness to histamine, but not on airway wall thickening, induced by
      intravenous administration of leukotriene C4 in guinea-pigs.
AB  - We studied the effect of i.v.administration of leukotriene (LT) C4 on bronchial
      responsiveness to histamine and airway wall thickening in guinea-pigs. The
      infusion of 3 micrograms/kg LTC4 for 1 h induced an increase of the relative
      thickness of the airway wall in peripheral bronchi, found by histological
      examination. In analysis of airway function, the infusion of 3 micrograms/kg LTC4
      for 1 h induced airway wall thickening and airway hyperresponsiveness to
      histamine administered i.v.at doses of 1.8 and 3.6 micrograms/kg. Thromboxane A2
      synthetase inhibitor OKY-046, which was administered perorally, inhibited the
      LTC4-induced airway hyperresponsiveness to histamine in a dose-dependent manner
      at doses from 30-100 mg/kg, but not the airway wall thickening induced by LTC4.

PMID- 8148579
TI  - Randomized placebo-controlled study on the characteristics and duration of action
      of surfactant treatment in premature lambs.
AB  - In a placebo-controlled study, the characteristics and duration of action of a
      commercially available bovine lung surfactant factor (LSF; 50 mg/kg body weight)
      were investigated in premature lambs at 124-127 days gestational age. Exact
      mating of ewes was controlled by progesterone hormone analysis. To minimize
      unwanted effects of narcotics through transplacental transfer to the fetus,
      spinal anaesthesia of the ewes was performed. The physiological status 'in utero'
      was demonstrated by arterial blood gas analysis (partial arterial oxygen pressure
      (PaO2), partial arterial carbon dioxide pressure (PaCO2) and arterial blood pH)
      of the fetus before umbilical cord ligature. The values for blood gases, blood
      pressure and lung mechanics measured after onset of ventilation and before LSF
      treatment were indicative of fetal maturity. Immediately after LSF treatment,
      PaO2 increased significantly, then decreased for about 2 h and finally stabilized
      on a plateau until the end of the experiment. In contrast, arterial blood pH and
      PaCO2 values normalized more slowly and remained normal for a longer period in
      the LSF group, whereas both parameters did not normalize in the placebo group.
      Total dynamic lung compliance also showed a slow improvement and remained on a
      higher level for a longer period than PaO2. Using a low respiratory rate it was
      possible to ventilate at lower peak inspiratory pressures and this resulted in
      higher compliance values. In conclusion, the presented data suggest that
      artificial ventilation greatly influences lung mechanics. Due to a relatively
      short substance effect concerning PaO2 we assume that higher or repeated doses of
      LSF may be necessary to produce sustained improvements in clinical trials.

PMID- 8148580
TI  - The integrity of the epithelium is a major determinant of the responsiveness of
      the dog bronchial segment to mucosal provocation.
AB  - The intact bronchial segment of the dog was used to investigate the role of the
      epithelium in modulating bronchial responsiveness: firstly, because it retains
      many of the properties of the airway wall including the separation of the mucosal
      and adventitial surfaces; and secondly, because airway tissue from dogs has been
      principally used in advancing evidence for epithelial relaxant substances. The
      development of tone by the airway smooth muscle was measured as an increase in
      luminal pressure of the isovolumic segment. Cholinergic excitatory and
      sympathetic inhibitory responses were obtained to electrical field stimulation.
      Responses to acetylcholine (ACh), carbachol, depolarizing K+ solution and
      vanadate (VO3-) applied to the mucosal surface were greatly attenuated both in
      sensitivity and reactivity compared with their effect on the adventitial surface.
      Mechanical removal of the epithelium greatly augmented these responses to agents
      in the lumen (ACh sensitivity increased 100-fold) to equal those by adventitial
      stimulation. The latter were unaffected by epithelial removal. No functional
      evidence for epithelial-derived inhibitory factors could be demonstrated. It is
      concluded that the impermeable nature of the epithelium acts as a barrier to
      diffusion of hydrophilic and charged molecules thereby producing large
      concentration gradients across the airway wall. A breach in the integrity of the
      epithelium enables molecules to gain access to the smooth muscle.

PMID- 8148581
TI  - [Social control of medical-technical progress].
AB  - The analysis emphasises the dependence of medical-technological progress on the
      zero fees for standard health services. Technologies with an additional or total
      self-payment are discriminated against by the patients and the physicians.
      Besides, a tendency to apply medical maximum standards was discerned. The
      enforcement of novel methods of diagnosis and therapy has been made substantially
      easier. In contrast, there are scarcely any incentives to introduce cost-saving
      technologies from the patient's point of view. The fixed budgets of the Health
      Structure Act will exercise greater pressure on introducing cost-cutting
      innovations.

PMID- 8148582
TI  - [Digoxin content in blood lipids of children, athletes, sports ground attendants
      and residents after content with dioxin-containing surface slag (Kieselrot)].
AB  - In 1991 it was discovered, that a large number of sporting grounds and
      playgrounds in Germany were covered with a waste slag material from a former
      copper smelter located at Marsberg, Germany. This material was found to contain
      high levels of PCDD/F ranging up to 100,000 TE/kg. The objective of the present
      study was to assess whether subjects sporting on such grounds had elevated levels
      of PCDD/F in blood. PCDD/F in blood fat was used as an indicator of the PCDD/F
      body burden. Additionally, six children and seven residents of a contaminated
      sporting and playground were examined. Generally, the levels of PCDD/F in blood
      fat were in the range of background levels in all subjects. Taking into account
      the effect of age, slightly elevated blood levels of PCDD/F were detected in
      children. The results show that the bioavailability of PCDD/F in the slag
      material is very low. However, from the preventive point of view children who
      might ingest slag material by hand-to-mouth-activities, should not play on such
      contaminated playgrounds.

PMID- 8148583
TI  - [Criteria for the determination of chronic exposure to hazardous substances via
      soil ingestion].
AB  - Legally recoverable protection of human health against pollutant effects must
      have for the enforcement in practice a technically comprehensible toxicological
      basis, i.e., a coherence or connection between the toxicological and legal
      definition of a dangerous situation must be found. For this purpose toxicological
      and socially accepted reference points in the unit "mg of pollutant amount
      absorbed per kg of weight per day" (mg/[kg of weight x d]) may be used to assess
      a danger in the sense a sufficient probability a damage to human health exists
      after exposure to certain pollutant concentrations. Based on the plausible
      toxicological assumption that above this reference point in case of an
      undisturbed course of action and by giving consideration to all exposure pathways
      a threshold of harmlessness including all groups of the population would be
      exceeded, criteria both for non-carcinogenic and carcinogenic substances or for
      substances suspected to cause cancer are being developed. These criteria allow to
      determine from which point the existence of a danger would be assessable as
      "sufficiently probable", and hence the required coherence between legal and
      toxicological view to be established.

PMID- 8148584
TI  - [Prognostic factors in malaria tropica--results of a 1963-1988 evaluation study
      in Germany].
AB  - A retrospective study was performed on all cases of malaria recorded in the
      Federal Republic of Germany between 1963 and 1988. The questionnaires evaluated
      by the Federal Bureau of Public Health showed a total of 8049 cases, of which
      3991 concerned malaria tropica, and 173 deaths. During this 26-year period, 90%
      of the patients suffering from malaria tropica had contracted the disease in
      Africa. Deaths from malaria had shown a constant figure of almost 10% between
      1963 and 1978, but after that there was a distinct drop. Differentiated analysis
      revealed that between 1979 and 1988 the death rate for malaria tropica acquired
      in Africa had been 3.3%. This was clearly dependent on chemoprophylaxis
      behaviour, on the time of initiation of treatment and on the age of the patients;
      if tablets were taken regularly, the death rate was 2.3%, rising to 3.1% on
      irregular intake and to 5.4% without chemoprophylaxis. If therapeutic measures
      were initiated on the 1st to 5th day of onset, the death rate was 0.6%, on the
      6th to 10th day 2.4%, on the 11th to 15th day 2.5% and on the 16th to 20th day
      16.7%. In the age group between 60 and over 60 years the lethality was 15.9%. In
      the course of this study the authors worked out a new malaria questionnaire for
      the Federal Bureau of Public Health.

PMID- 8148585
TI  - [Employees and regular customers of restaurants and discos as transmitters of
      tuberculosis].
AB  - It is often maintained that tuberculosis is a disease affecting only individuals
      and that it scarcely causes epidemics any longer. Public health authorities state
      that this notion needs to be considerably corrected. Precisely because the
      incidence of tuberculosis has, to a large extent, been declining over past
      decades, the point in time for initial infection has been largely pushed back
      into the middle-aged group. In particular, alcoholics and those with a weakened
      immune system are subject to tuberculosis diseases, which represent a risk for
      contact persons. Those most at risk are young people whose immune system has
      never had to combat TB. Above all, if an unknown bacterial source, a regular
      customer, a waiter or disc jockey, coughs in a restaurant or disco, there can
      easily be a small or even large epidemic of tuberculosis. Especially today,
      therefore, importance is placed on consistent "environmental" examinations by the
      public health authorities in accordance with the Federal Law on Epidemics. The
      necessity and effectiveness of this measure is demonstrated using the example of
      an outbreak of tuberculosis in a disco, whereby a waitress and a disc jockey were
      confirmed as TB cases in a routine examination. Within five years, 19 active lung
      tuberculosis cases were discovered among those going to that disco. Three of
      those infected have respectively caused two further cases of the disease in their
      close contact circles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148586
TI  - [General practice of salmonella control from the viewpoint of the public health
      office--a report of experiences from Cottbus and the Brandenburg area].
AB  - Internationally, an enhanced incidence of the PT4 plasmid is seen in S.
      enteritidis. Parallel to this, the incidence is also increasing in the new German
      Land of Brandenburg. The Federal law governing the control of epidemics--which is
      now also valid in Brandenburg due to the reunification of Germany--demands that
      strict controls are enforced wherever there are institutions for children,
      including controls of the environment of such institutions. As a result of this
      enforcement, it was possible to identify 947 salmonella infections in the Cottbus
      district in 1992, 82.15% of which were due to S. enteritidis with identification
      of PT4 plasmid. The question is now raised as to whether the high infectious dose
      of S. enteritidis with PT4 plasmid still applies and whether the prescribed
      antiepidemic measures are still necessary in respect of assuming--as the law
      demands--that strains with PT4 plasmids are to be considered equal in respect of
      all other salmonella serovars. More than 1000 children under 2 years of age are
      being cared for in the kindergartens and creches of Cottbus who would be
      particularly exposed to infections not transmitted by food intake alone. But
      there is a shortage of funds which is a serious obstacle to antiepidemic
      measures. A note of warning is sounded against restricting investigations to food
      intake only. Particular attention is drawn to the crying need for more research,
      for interdisciplinary cooperation and stricter measures to fight infection.

PMID- 8148587
TI  - [Short-term occupational disability].
AB  - The present political discussion about absenteeism in industry and introduction
      of days of absence in case of sickness emphasises the amount of short-term
      sickness cases. More or less openly the misuse of continued salary payment via
      "unauthorized" working inability is discussed: this is often connected with the
      increased absenteeism on Mondays and Fridays. From the point of view of the Legal
      Health Insurances this thesis of misuse is investigated in an analysis of cases
      of short-term work disability.

PMID- 8148588
TI  - [Paraplegic patients are "severely disabled"].

PMID- 8148589
TI  - [Sexual abuse of children (section 176 StGB)--general practice of forensic
      perpetrator assessment].
AB  - Data from 28 paedophilic persons seen on the occasion of forensic psychiatric
      assessment are presented. These persons represented a remarkable 25% proportion
      of all sexual offenses seen at the department of forensic psychiatry between 1986
      and 1992 (n = 111). Paedophilics were on the average elderly persons who tended
      to have a lower education level and achieved poorer results in intelligence
      testing (WIP-72). In their medical history, data on brain injury and child
      development retardation were not significantly more often available than from
      other sexual delinquents. Comparing persons accused because of paedophilic acts
      with those accused because of other sexual offenses the proportion of recurrent
      sexual offenses was not significantly different. Personality traits of
      paedophilics (FPI-A1) were dominated by signs of passive and dependent behaviour.

PMID- 8148590
TI  - [Response to Ewers et al.: Determination of heavy metal pollution of soil and
      garden produce from Stolberg personal gardens and lead and cadmium burden of
      Stolberg small scale gardeners].

PMID- 8148591
TI  - [Health and life style].
AB  - In the theoretically top-heavy, demanding and over-fastidiously artificial and
      abstract variety of Marxism, some seeds of certain anthropological and biological
      "constants" of illness and health had been at least sown. This notwithstanding,
      society as conceived and practised in the former so-called German Democratic
      Republic was governed by an oversocialised image of Man. The positive core of
      this tendency to oversocialisation was the axiom that humanising Man coincided
      with humanising Man's social environment. Negative sequels of such
      oversocialisation of the human image were, among others, separating Man's
      anthropological mode of existence from the social context; underestimating the
      role of borderline situations in human life (as conceived by Jaspers); and
      massive intrusions by the State into Man's private sphere. Last but by no means
      least, the vision of the emerging new "rich human being", of a "human being in
      need of the entirety of human manifestations of life" (Marx) proved to be nothing
      but a Utopian abstraction. One of the arguments brought forward was that chances
      to acquire and preserve health are actually options for translating aims of life
      into reality by means of the possibilities of individual development of one's
      innate propensities, possibilities offered to Man by and within the framework of
      social structures. It follows from this manner of reasoning that both the
      political and the intellectual strata in the German Democratic Republic were
      convinced that their ideological construction of "congruence" between the
      interests of society and those of the individual was indeed a reality.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8148592
TI  - [Expert assessment and counseling--a contradiction?].
AB  - This article concerns the rules and regulations governing the Federal German
      compulsory (statutory) health insurance which, among other ordinances, define the
      tasks of a so-called "Medical Service of the Statutory Health Insurance". The
      definitions given under the heading "Expertizing and Consultation" create a field
      of tension between the activities of advising the insured patient on the one hand
      and giving an expert opinion to the insurance body on the other, both functions
      being exercised by one and the same doctor. Four examples from daily practice are
      given to illustrate this, each example covering a different kind of medical
      activity. Against the background of his job to prepare an expertise for the
      insurance body the doctor confronts the insured patient: in the first example, he
      has to examine whether the kind of medical care for which the insurance body must
      pay is feasible from the cost viewpoint (or to suggest an alternative, cheaper
      method); in the second example, he removes well-founded doubts regarding the
      patient's inability to work, at the request of the employer; in the third case,
      he examines a prescribed or desired medical treatment or cure, and in the fourth
      case he examines the need for an adjuvant or remedial measure before this is
      sanctioned by the insurance body. These case reports show that there is no
      contradiction between consulting and expertizing: the results of expertizing can
      be conveyed to the patient in a comprehensible manner only by advising the
      patient accordingly. The expertizing doctor is no longer anonymous when he gives
      advice to the patient, and this is a challenge--in respect of competence, human
      understanding, and ability to face and resolve conflicts.

PMID- 8148593
TI  - [Significance of European integration for public health in Germany].

PMID- 8148594
TI  - [The development of European public health from the viewpoint of one country].
AB  - Health politics and health systems of the European regions will be influenced by
      article 129 of the Maastricht treaty. Public health and health information are
      keywords. Science and the relevant associations will have to pay attention to
      this development.

PMID- 8148595
TI  - [Nine months German Statutory Health Insurance Structural Reform Law--effects and
      perspectives].
AB  - In 1992 the German Statutory Health Insurance body was in the red by about 9,000
      million DM and had the highest membership fees ever since it was created. Costing
      analysis revealed the following reasons for this enormous deficit: too expensive
      hospital financing a continually growing number of doctors and dental surgeons
      unrational drug prescription and supply. Of course, medical progress and
      demographic development are very significant costing factors. When assessing the
      impact of the Structural Reform Legislation we must differentiate between purely
      cost-reducing measures and structural changes. Cutting down the budgets in
      essential areas of compensation payment and slashing doctor's fees are like
      putting your foot down on the brake pedal. The statutory health insurance data
      for the first two quarters showed: doctors +3.4%, dental surgeons -4.3%. Limiting
      the budget for drugs to about 24,000 million DM and for remedial items to about
      4,000 million DM with a possible collective slashing of the fees paid to doctors
      if these budgets were exceeded, proved to be an effective cost-reducing measure.
      In the case of drugs costs went down by 20.1% compared with the previous year
      (1992) due to an halt in prices charged by the drug industry and greater
      financial participation on the part of the patients. Prescriptions were reduced
      to a comparatively slight extent (1-2%), but the mode of prescription was much
      more economical.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148596
TI  - [Do legal regulations obstruct adequate quality assurance in the area of drug
      therapy?].
AB  - In Germany the quality of drug therapy suffers from the lack of transparency of
      an overloaded drug market, from the turnover-oriented information strategies of
      the pharmaceutical industry and from the lack of prescribing transparency and
      quality control of the individual doctor. After an analysis of the present
      deficient situation in the area of drug therapy the following paper discusses
      strategies to improve structure as well as process quality. It also stresses the
      necessity of implementing a legal framework to analyse individual patients'
      records aimed at controlling the quality of therapy. Because of problems with
      confidentiality continuous patient record linking is not allowed although it is a
      precondition for an adequate control of the patients progress and the quality of
      results.

PMID- 8148597
TI  - [Comparison of public health systems within the European Community].
AB  - Only two out of three ideal types of health care systems can be observed in the
      European Community (EC): Centrally planned systems (countries with a national
      health service) and systems managed mainly by associations of health insurance
      funds and also of providers (countries with a social insurance system). We find
      no country with a market-type health care system in Europe. Both types of systems
      occurring in the EC are compared with each other, both with regard to their ideal
      types and also to their actual operations when judged on grounds of financing and
      production of health care. When seen as ideal types, we note considerable
      differences. Real types however exhibit only gradual differences. The shares of
      major subcategories of health spending differ widely between EC countries. These
      differences, however, cannot be attributed to the different health care systems.
      Similar observations can be made regarding different forms of payment for
      hospital care and for physician services and also regarding the share of total
      health expenditure in GDP.

PMID- 8148598
TI  - [Pathogenetic and salutogenetic factors--personality development and addiction
      career].
AB  - The problem of pathogenetics and salutogenetics factors for addiction are
      examined. Drug use is classified in each case as a specific expression of
      personal problem processing and psychosocial conflicts. The differential approach
      to therapy from this model is discussed and a case is made out for a stronger
      integration of pathogenetic and salutogenetic personality organisation in the
      diagnosis and therapy of addiction.

PMID- 8148599
TI  - [Work capacity--a central category of practical social medicine].
AB  - Gainful employment-related performance capacity is a central but rarely
      considered category of practical social medicine. Its evaluation belongs to the
      workday routine of social physicians. Special difficulties arise if chronic pain
      disorders are to be evaluated, especially in chronic "nonspecific" cases, i.e. in
      the absence of biomedically relevant signs. Employment-related performance is
      conceptualised as a multidimensional construct with several latent variables. It
      integrates and extends the domains of "impairments" and "disabilities" of the
      International Classification of Impairments, Disabilities, and Handicaps (ICIDH)
      of WHO. Three basic dimensions are distinguished: one comprising biomedical, the
      other psychological, the third function-related variables. They are specified
      within a multidimensional model of employment-related performance. This includes
      different components of the perception and appraisal of pain, concomitant bodily
      complaints (e.g. vital exhaustion), psychological impairments as helplessness or
      anxiety, special facets of the pain behaviour, and functional limitations and
      allows an estimate of the chronification and prognosis of the pain problem. Some
      diagnostic measures are still inadequate in respect of established clinimetric
      standards. In particular, assessment of functional limitations requires further
      development and research.

PMID- 8148600
TI  - Humanised technology and compassionate competence.

PMID- 8148601
TI  - A study into the uses and effects of do-not-resuscitate orders in the intensive
      care units of two teaching hospitals.
AB  - Do-not-resuscitate (DNR) orders pose many ethical and moral dilemmas for health
      professionals. When placed in the context of an Intensive Care Unit (ICU), these
      dilemmas are magnified. Data were obtained on all admissions to two ICUs over a 3
      month period, using a descriptive survey design. During this period 26 patients
      were deemed not for resuscitation, all of whom were suffering from multiple
      medical problems. Nursing dependency was found to be unaltered by a DNR order.
      Medical intervention was unaltered in 13 (52%) of the DNR patients after an order
      was made, but in the remaining (12) 48% some therapy was withdrawn. One patient
      was admitted to ICU with a DNR order already having been made on an elderly care
      ward. 24 (92%) of the DNR patients died in ICU, with a further patient dying on a
      general ward, and another still an inpatient 3 months after leaving ICU. The
      patients' family were involved in the discussions regarding resuscitation in 20
      (80%) of the cases, and the nursing staff in 17 (68%). The medical input was at a
      senior level, although the order was generally documented by more junior staff.
      In six (24%) cases DNR orders were verbal only. These units demonstrate generally
      good practice regarding DNR decision-making and nursing care. However, explicit
      documentation is necessary in all cases.

PMID- 8148602
TI  - Nurses' attitudes toward computerised care plans in intensive care. Part 2.

PMID- 8148603
TI  - Maintaining the patency of transduced arterial and venous lines using 0.9% sodium
      chloride.
AB  - Using dilute concentration of heparin in continuous flush systems for arterial
      and venous invasive cannulae is an established practice in intensive care units
      (ICUs) throughout the UK. It is, however, practical to maintain the patency of
      these lines using 0.9% sodium chloride, thus reducing the possibility of drug
      interactions, systemic anticoagulation and cost. A small feasibility study was
      carried out in a 10-bedded general ICU on both arterial and venous lines using
      0.9% sodium chloride over a 3-month period. The study has subsequently changed
      unit policy.

PMID- 8148604
TI  - Introducing a change of nursing model in a general intensive therapy unit.
AB  - This paper focuses on the management of change in the context of health care and
      looks specifically at methods of introducing a new model of nursing into a
      general Intensive Therapy Unit (ITU). Rationale for change is discussed, change
      theory is appraised and a strategy for implementation, management and evaluation
      of change is provided.

PMID- 8148605
TI  - Does nurse turnover mean nurse wastage in intensive care units.
AB  - It has been claimed that the turnover rate of nurses working in Intensive Care
      Units (ICUs) is higher than in other areas of nursing; very little statistical
      evidence was found to support this claim. A questionnaire was designed to
      discover the reasons for nurse turnover among intensive care nurses. 45 nurses
      who had left the three ICUs of a large teaching hospital took part in the survey
      providing quantitative and qualitative data. High levels of dissatisfaction were
      found for career development, pay and clinical regrading, these being the main
      cause of turnover among the nurses who responded. Other causes were moving to
      another geographical area and the need for flexible hours. These findings can
      partly be explained by role conflict.

PMID- 8148606
TI  - Causal and emotional factors related to work stress in ICU nursing staff. The
      importance of accurate measurement.
AB  - This study was designed to determine the degree of intervention of causal and
      emotional factors in work stress in intensive care unit (ICU) nursing staff. A
      questionnaire to assess stress causes (27) and associated emotions (33) was given
      to 123 people (85 registered nurses and 38 auxiliary nurses) aged 22-56, working
      in ICUs in different hospitals in Palma de Mallorca. Descriptive and factorial
      analyses were carried out. Respondents gave most stress causes a medium score
      (3.5-6.5 points), the highest values corresponding to staff shortage (mean =
      6.71), bad management organisation (mean = 6.65) and little free time (mean =
      6.5). These causes are grouped in seven factors which account for 65.51% of
      variance and are particularly related to organisational problems, training and
      personal relationships, work demands and physical and emotional overload. The
      most important emotions for this sample are: responsibility (mean = 6.61),
      impotence (mean = 6.23) and desire to excel (mean = 6.080). Such emotions are
      divided into seven factors which explain 65.31% of the variance and define states
      of personal satisfaction, depersonalisation, anxiety, low self-esteem,
      helplessness and arrogance. Surprisingly, the main factor with the value 5.08 and
      a variance of 15.42%, corresponds to positive or pleasant emotions. The results
      corroborate previous research findings on work stress, provide a simplified tool
      for assessing this and show the need to quantify the degree of such
      manifestations in the assessments.

PMID- 8148607
TI  - Touch and visualisation to facilitate a therapeutic relationship in an intensive
      care unit--a personal experience.
AB  - This paper describes how the nature of touch was explored and utilised in nursing
      practice to promote a therapeutic relationship between nurse and client in an
      intensive care setting. It explains how this, and other complementary therapies
      such as visualisation and relaxation techniques, were used to facilitate a
      counselling situation, and also to effect the resolution of acute anxiety as an
      alternative to the traditional allopathic approach.

PMID- 8148608
TI  - Ethical decision-making in intensive care: a nurse's perspective.
AB  - Technology has increased our ability to sustain life, but to what end? Ethical
      dilemmas abound in intensive care units (ICUs), but in the author's experience
      nurses are rarely formally involved in ethical decision-making. Should nurses be
      involved? This article is an attempt to answer this question by considering the
      unique position of an intensive care nurse, the stress caused by ethical
      dilemmas, the ethical and legal responsibilities of the nurse and the educational
      and psychological factors influencing the decision-making process. The current
      involvement of nurses in ethical decision-making is reviewed and a framework for
      ethical decision-making is suggested. Implications for education and practice are
      drawn from the discussion.

PMID- 8148609
TI  - Personal cost, caring and communication: an analysis of communication between
      relatives and intensive care nurses.
AB  - Much of health care is seen as 'communication-centred' (Smith & Bass 1982) and
      the interpersonal nature of nursing gives this view particular relevance. The
      potential contribution to patient well-being which is offered by good
      communication is being recognised by professional service providers and consumers
      alike. Whilst relatives or 'significant others' have an important impact on
      patient well-being, recognition of their own needs is becoming more evident. This
      paper, therefore, is intended to focus attention on communication between nurses
      and patients' relatives in critical care settings. Needs of relatives are
      discussed along with an analysis of nurses' responses to these needs, and nurses'
      apparent reluctance to be involved is explored. A critical appraisal of the
      literature reveals compelling arguments for a decisive contribution by nurses to
      this area of care. Initiatives aimed at placing communication needs of relatives
      more firmly within a nursing remit are then explored. Whilst intensive care units
      (ICUs) may generally demonstrate good practice in relation to communicating with
      relatives it is suggested that exploration of concepts surrounding both the
      nature of nursing and caring may offer valuable insights into this aspect of
      critical care nurses' role.

PMID- 8148610
TI  - Recovery units: the future of postoperative cardiac care.
AB  - In the current climate of scarce financial resources health care managers have
      had to question the financial viability of a 36-hour stay in an ICU for patients
      undergoing cardiac surgery. The management of this group of patients has had to
      be reexamined. The solution to this problem appears to lie in the utilisation of
      a designated recovery area for the management of this group of patients. This
      paper is an audit of the first 100 cardiac patients who recovered in such a
      designated recovery unit. The audit examines types of operations performed,
      average length of time patients required artificial ventilation, blood loss in
      the first 4h, average length of stay in hospital, and postoperative
      complications. Possible methods of improving the utilisation of a recovery area
      in the management of postoperative cardiac patients are discussed. The conclusion
      is that utilisation of a designated recovery area for the immediate postoperative
      management of cardiac surgical patients is a financially viable alternative to an
      intensive care environment. More importantly, high quality service and care is
      maintained without increasing the utilisation of resources.

PMID- 8148611
TI  - EXAFS studies of Fe(III)-phosvitin at high metal to protein ratios.
AB  - The stereochemistry of the Fe(III) binding sites in chicken egg phosvitin (PST)
      at very high iron content, in solution and as a powder, has been investigated
      through EXAFS spectroscopy. We found that the EXAFS spectra obtained for aqueous
      PST solutions at metal:protein ratios of 20:1 and 40:1 are very similar to those
      previously obtained by us on a Fe10PST sample. In all cases the iron ions are
      octahedrally coordinated by oxygen atoms of the serine-bound phosphate groups and
      by other ligands from either the protein or the solvent. The average metal-donor
      atom distance is 1.94 A. At variance, the EXAFS results for a Fe50PST powder
      sample suggest the occurrence of a switch in iron coordination from octahedral to
      lower coordination numbers (5,4). The average iron-oxygen distance is virtually
      unchanged; apparently, four iron ligands are provided by four different
      coordinate phosphate groups from the phosphorylated serine residues abundant in
      the protein. This finding contains interesting implications for the structure
      function relationships of this intriguing protein.

PMID- 8148612
TI  - Structure of vulnibactin, a new polyamine-containing siderophore from Vibrio
      vulnificus.
AB  - A new siderophore named vulnibactin has been isolated from low iron cultures of
      Vibrio vulnificus, a human pathogen. The structure was established as N-[3-(2,3
      dihydroxybenzamido)propyl]-1,3-bis[2-(2-hydroxy-phenyl)- trans-5 - methyl-2
      oxazoline-4-carboxamido]propane by a combination of acid hydrolysis, nuclear
      magnetic resonance spectroscopy and positive fast atom bombardment mass
      spectrometry. Vulnibactin is characterized as containing one residue of 2,3
      dihydroxybenzoic acid as well as two residues of salicylic acid, both of which
      are involved in the formation of oxazoline rings with L-threonine bound to a
      norspermidine backbone. In addition, two other compounds with siderophore
      activity were purified and their structures were also determined. These two
      compounds provided further support for the structure of vulnibactin.

PMID- 8148614
TI  - Cadmium in blood in Alzheimer's disease and non-demented subjects: results from a
      population-based study.
AB  - Blood cadmium concentrations were studied in Alzheimer's disease (AD) and non
      demented subjects. The 29 individuals were randomized from the ongoing population
      survey on ageing and dementia in Stockholm, the Kungsholmen Project. Smokers had,
      as expected, higher cadmium levels than non-smokers. Cadmium concentrations in
      blood were related to diastolic blood pressure in non-smoking, non-demented
      individuals. In contrast to previous reports no differences in blood cadmium
      levels were found between AD sufferers and non-demented subjects. Furthermore,
      there were no correlations between cadmium levels in blood and age or cognitive
      functions. The importance of quality assurance in sample collection and analysis
      of cadmium as well as scrutinizing smoking habits is emphasized.

PMID- 8148613
TI  - Management of dietary essential metals (iron, copper, zinc, chromium and
      manganese) by Wistar and Zucker obese rats fed a self-selected high-energy diet.
AB  - The balances and content of essential elements (iron, copper, zinc, chromium and
      manganese) in the body of Wistar, Zucker lean and Zucker obese rats fed a
      reference or cafeteria diet from day 30 to 60 after birth have been studied.
      Intestinal iron absorption compensated for low iron content of the cafeteria diet
      and the extra needs of growth and fat deposition. It can be assumed that the
      altered energy regulation processes that afflict the genetically obese rat are
      not directly related to altered iron metabolism. Obese Zucker rats had lower
      copper tissue concentrations than lean rats, but when fed a cafeteria diet the
      differences between Zucker rats strains disappear. This cannot be traced to large
      differences in diet copper concentration. A low diet availability of zinc--such
      as that of cafeteria-fed fa/fa rats--is easily compensated for by increasing
      absorption. So, as a consequence, we can conclude that genetic obesity did not
      impair zinc absorption. There was no deficit of zinc in any of the groups
      studied; the rats have enough capacity to extract zinc within a wide range of
      dietary concentrations. The absorption of dietary chromium was inversely
      proportional to its concentration. The ability to extract chromium from the diet
      and the very low urinary losses are a consequence of its scarcity in most dietary
      items. Despite wide variations in the manganese of the diets, the absorption
      rates were practically unchanged except for obese rats fed the cafeteria diet. It
      seems that this low absorptive capacity is enough to supply the rat with the
      manganese it needs, since a sizeable--but subjected to 8-fold-span variations-
      proportion is lost in the urine. This alone points towards a considerable excess
      of manganese in both diets studied. Obesity does not have a significant effect on
      the abilities to absorb and retain minerals, since these processes were more
      related to dietary availability. Management of essential metals by obese rats
      depends whether this condition is genetic or induced by diet. Most of the
      differences observed can be related to differences in diet concentration, to the
      excess fat content or different metabolic attitude to use substrates of obese
      animals. The data presented show that the cafeteria diet used adequately serves
      the mineral needs of the rat, since the rat adapts its absorbing and retaining
      strategies to match the dietary availability of these minerals.

PMID- 8148615
TI  - Evidence for the interference of aluminum with bacterial porphyrin biosynthesis.
AB  - Aluminum (0.74 mM) was found to retard bacterial growth, and enhance porphyrin
      formation and excretion in Arthrobacter aurescens RS-2. Coproporphyrin III was
      shown to be the main porphyrin excreted by aluminum-exposed A. aurescens RS-2
      cultures and by RS-2 cultures grown under anoxic conditions. Synthesis and
      excretion of porphyrins in A. aurescens RS-2 increased in a dose-dependent manner
      when the bacteria were exposed to increasing aluminum concentrations. Incubation
      of A. aurescens RS-2 with delta-aminolevulinic acid (delta-ALA, 1.2 mM) brought
      about the intense formation and excretion of porphyrins by the cells, in the
      presence or absence of aluminum. delta-ALA slightly enhanced the toxicity of
      aluminum towards RS-2 bacteria. Furthermore, the intracellular concentration of
      heme was reduced by 63.9 +/- 8.67% in aluminum-exposed RS-2 bacteria when
      compared with control cultures. The results are discussed in light of the recent
      finding concerning aluminum toxicity and porphyrin biosynthesis in
      microorganisms.

PMID- 8148616
TI  - Distribution and excretion of lanthanides: comparison between europium salts and
      complexes.
AB  - Europium (152,154Eu) was intravenously injected into rats as: (i) the chloride
      salt at pH 7.4, (ii) the chloride salt at pH 3, (iii) the albumin complex and
      (iv) the DTPA complex, and tissue uptake was determined 24 h later. For the
      chlorides, the target organ for uptake was liver (about 60% of dose) whilst
      europium complexes were rapidly excreted in urine and were predominantly taken up
      into the kidney (about 0.5% of dose) and bone. Liver uptake of EuCl3, pH 7.4,
      corresponded to that of a colloidal material with most 152Eu present in the non
      hepatocyte population; however, EuCl3, pH 3, was handled in a different manner,
      with significant uptake by hepatocytes. The differing tissue distributions of
      EuCl3 and Eu-albumin suggest that plasma albumin does not readily bind injected
      EuCl3. Renal uptake of europium, although a relatively low proportion of the
      injected dose, was associated with many subcellular fractions, including
      lysosomes, suggesting significant intracellular uptake and thus possible
      retention.

PMID- 8148617
TI  - HPLC separation of enterobactin and linear 2,3-dihydroxybenzoylserine
      derivatives: a study on mutants of Escherichia coli defective in regulation
      (fur), esterase (fes) and transport (fepA).
AB  - Reversed-phase HPLC separation of enterobactin and its 2,3-dihydroxybenzoylserine
      derivatives was used for a comparative analysis of mutants of Escherichia coli,
      defective in the regulation of enterobactin biosynthesis (fur), enterobactin
      transport (fepA) and enterobactin esterase (fes). A complete separation of all
      2,3-dihydroxybenzoylserine compounds was achieved: the monomer (DHBS), the linear
      dimer (DHBS)2 and trimer (DHBS)3, the cyclic trimer, enterobactin, as well as 2,3
      dihydroxybenzoic acid. The production of all these compounds was followed after
      ethylacetate extraction from acidified culture fluids. Enterobactin was found to
      be the predominant product in all mutant strains. The mutant strains behaved
      differently with regard to the breakdown products. All degradation products, such
      as DHBS, (DHBS)2 and (DHBS)3, were detected in the overproducing fur mutant where
      both transport and esterase are still functioning, while only the monomer, DHBS,
      was detected in the fepA mutant and no degradation was found in the esterase
      deficient fes mutant. From the pattern of breakdown products it may be inferred
      that the esterase acts in two different ways, depending on whether transport is
      functioning or not. Thus, esterolytic cleavage of ferric enterobactin after
      entering the cells results in a mixture of all three hydrolysis products, i.e.
      DHBS, (DHBS)2 and (DHBS)3, while cleavage of iron-free enterobactin subsequent to
      its biosynthesis yields only the monomer. Thus, the results of quantitative HPLC
      analysis of enterobactin and its breakdown products show that different
      enterobactin esterase products arise, depending on whether iron is bound to
      enterobactin or not.

PMID- 8148618
TI  - Comparisons between the inorganic content of healthy and hypertensive rat tissues
      by inductively coupled plasma-mass spectrometry.
AB  - The inorganic contents of bone, brain, erythrocyte, heart, kidney cortex, kidney
      medulla, liver, lung, muscle and plasma from spontaneously hypertensive rats were
      compared with those of the same tissues from healthy Sprague-Dawley rats. A
      general inductively coupled plasma-mass spectrometry method developed for multi
      element determinations of most of the elements present in biological tissues was
      used. Variations were found not only for major elements, as expected, but also
      for many trace elements in several tissues.

PMID- 8148619
TI  - Structure of acinetoferrin, a new citrate-based dihydroxamate siderophore from
      Acinetobacter haemolyticus.
AB  - From low-iron cultures of Acinetobacter haemolyticus ATCC 17906, a new
      hydroxamate siderophore was purified by XAD-7 adsorption followed by preparative
      thin layer chromatography. The siderophore, named acinetoferrin, released citric
      acid, 1,3-diaminopropane and (E)-2-octenoic acid upon hydrolysis with HCl,
      reductive hydrolysis with HI and oxidation with periodate, respectively.
      Structure elucidation by a combination of NMR spectroscopy and positive fast atom
      bombardment mass spectrometry revealed that acinetoferrin is a derivative of
      citric acid, both of its terminal carboxyl groups being symmetrically amide
      linked with the 1-amino-3-(N-hydroxy-N-2-octenylamino)propane residues. The (E)-2
      octenoic acid is novel as a component of the siderophores.

PMID- 8148620
TI  - In vitro studies on the DNA impairments induced by Cr(III) complexes with
      cellular reductants.
AB  - The influence of Cr(III) complexes with ascorbic acid, cysteine and glutathione
      on DNA has been studied spectrophotometrically and chromatographically. The toxic
      and genotoxic activities of these complexes were also investigated. It was found
      that these complexes bind to DNA weaker than hexaaqua Cr(III) complexes. It could
      be explained through the greater strength of the bi- and tridentate ligands
      coordinated to chromium in comparison to water molecules. The formation of DNA
      DNA intermolecular bonds and DNA interstrand cross-linking has been also
      observed. These complexes were found to be non-toxic and non-genotoxic in the
      bacterial test.

PMID- 8148621
TI  - Effect of nickel on certain physiological and biochemical behaviors of an acid
      tolerant Chlorella vulgaris.
AB  - This study concerns the inhibitory effects of acid pH and nickel on growth,
      nutrient (NO3- and NH4+) uptake, carbon fixation, O2 evolution, electron
      transport chain and enzyme (nitrate reductase and ATPase) activities of acid
      tolerant and wild-type strains of Chlorella vulgaris. Though a general reduction
      in all these variables was noticed with decreasing pH, the tolerant strain was
      found to be metabolically more active than the wild-type. A reduced cation (NH4+,
      Na+, K+ and Ca2+) uptake, coupled with a facilitated influx of anions (NH4+,
      PO4(3-) and HCO3-), suggested the development of a positive membrane potential in
      acid tolerant Chlorella. Nevertheless, a tremendous increase in ATPase activity
      at decreasing pH revealed the involvement of superactive ATPase in exporting H+
      ions and keeping the internal pH neutral. A difference in Na+ and K+ efflux of
      the two strains at decreasing pH suggests there is a difference in membrane
      permeability. The low toxicity of Ni in the acid tolerant strain may be due to
      the low Ni uptake brought about by a change in membrane potential as well as in
      permeability. Hence, the development of superactive ATPase and a change in both
      membrane potential and permeability not only offers protection against acidity,
      but also co-tolerance to metals.

PMID- 8148622
TI  - Community nursing: role boundaries should be changed.

PMID- 8148623
TI  - Why does nursing theory fail in practice?

PMID- 8148624
TI  - Role of the nurse in thrombolytic therapy.
AB  - The introduction of thrombolytic therapy has led to significant changes in the
      management of patients with myocardial infarction. This article reviews the
      current literature and discusses the role of the nurse and the implications for
      practice.

PMID- 8148625
TI  - Effects of noise in hospitals.
AB  - Excessive noise in health care settings can induce headaches, cause irritability,
      prolong wound healing and increase sensitivity to pain. Simple measures, such as
      wearing soft-soled shoes, closing doors to areas with excessive noise (the
      television or sluice rooms) and choosing equipment with quieter alarms, can
      improve patient outcomes and result in a better working environment for hospital
      staff.

PMID- 8148626
TI  - Reflection, the art and science of nursing and the theory-practice gap.
AB  - In their daily practice, nurses appear to encounter difficulties in incorporating
      science into the art of nursing and in bridging the gap between theory (which is
      often developed separate from practice) and practice itself. Indeed, there is a
      debate within nursing itself as to whether nursing is an art, a science, or both
      an art and a science.

PMID- 8148627
TI  - Telling children about their impending death.
AB  - Although some parents and health care staff believe that knowledge of impending
      death should be withheld from children to protect them, seriously ill children
      usually have an awareness of death. Denial of this by parents and staff may
      increase the child's stress. Nurses must address the question: asked by Rimmer
      (1993): 'To whom does the information of the diagnosis belong?'

PMID- 8148628
TI  - Nurse-aid management of psychiatric emergencies: 3.
AB  - The previous article in this series highlighted the nursing management of
      depression, mania and anxiety. This article considers the nurse-aid interventions
      for another disturbed affective state, aggression.

PMID- 8148629
TI  - Care of a handicapped woman with metastatic breast cancer.
AB  - Reflection can be utilized by nurses as a learning process to help them expand
      and develop their clinical knowledge and skills to directly benefit client care.
      Patients with advanced diseases that cannot be cured are part of a low status
      group which renders them vulnerable. As nurses we have control and power and it
      is our professional duty and privilege to use it on our patients' behalf. The
      early detection of cancer in the mentally handicapped population is often
      difficult. For nurses to feel confident in dealing with malignant wounds, they
      should also have a basic knowledge of the factors leading to malignant lesions
      and the factors that influence wound healing. Each malignant ulcer is unique,
      requiring individual assessment. The preferred conventional treatment for locally
      advanced breast cancer is palliative radiotherapy.

PMID- 8148630
TI  - A definition of nursing based on nurturing.

PMID- 8148631
TI  - Audit of head injury management in the Northern Region. Northern Regional Head
      Injury Group.
AB  - Head injury is a major cause of mortality and morbidity in the UK and is more
      prevalent among children and young adults. However, certain factors that
      contribute to deaths and brain damage can be audited. This article describes an
      audit of head injury management conducted by the Northern Regional Head Injury
      Group.

PMID- 8148632
TI  - Postconcussional disorder: time to acknowledge a common source of neurobehavioral
      morbidity.
AB  - Closed head injuries are common, affecting approximately 2 million people
      annually in the United States. The majority of these are "mild" in the sense of
      not being associated with prolonged unconsciousness, intracranial bleeding, skull
      fracture, or protracted periods of confusion. Yet a proportion of such "mild"
      injuries are accompanied by persisting cognitive, vegetative, and affective
      behavioral sequelae, some of which affect day-to-day life. We argue that there is
      sufficient research to indicate that postconcussional symptoms occur and that
      they tend to have a predictable configuration. It is necessary to recognize the
      existence of "Postconcussional Disorder" in our nosology in order to provide more
      prompt diagnosis and management and to facilitate scholarly communication and
      research regarding this important neurobehavioral disorder.

PMID- 8148633
TI  - A survey of the phenomenology and pharmacotherapy of compulsive and impulsive
      aggressive symptoms in Prader-Willi syndrome.
AB  - Prader-Willi Syndrome (PWS) is a congenital disorder characterized by hyperphagia
      as well as by other behavioral disturbances such as self-mutilation and temper
      outbursts. Some of these symptoms have been reported to respond to psychotropic
      medications. A systematic survey was conducted to gather information on the
      phenomenology and pharmacotherapy of compulsive and impulsive-aggressive symptoms
      in PWS. Both compulsive and impulsive-aggressive symptoms are frequent in this
      population. Pharmacotherapeutic intervention may have a role in the management of
      these symptoms. Rigorous diagnostic and treatment studies should be undertaken in
      this population.

PMID- 8148634
TI  - The Delirium Rating Scale in a psychogeriatric inpatient setting.
AB  - The Delirium Rating Scale (DRS) has been shown to be a valid instrument for
      identifying and grading the severity of delirium in patients admitted to a
      general hospital for medical or surgical treatment. However, its accuracy in
      identifying delirium among elderly patients admitted to a psychiatric hospital
      for evaluation and treatment of psychiatric illness has not been previously
      addressed. The DRS was administered to 791 elderly patients who were
      consecutively admitted to a psychogeriatric unit; 70 met DSM-III-R criteria for
      delirium. A DRS threshold score of > or = 10 correctly identified delirious
      patients with a sensitivity of 94% and a specificity of 82%. Both psychosis and
      cognitive impairment appeared to falsely elevate the DRS score in this
      population.

PMID- 8148635
TI  - Smooth pursuit eye movement abnormality in severe major depression: effects of
      ECT and clinical recovery.
AB  - Smooth pursuit eye movement (SPEM) dysfunction is a putative genetic marker for
      schizophrenia, but it has also been described in major depression. The authors
      longitudinally evaluated effects of clinical state on SPEM quality in patients
      with depression. Prior to ECT, SPEM abnormality characterized 42% of 24 severely
      depressed patients, 60% of 30 schizophrenia patients, and 5% of 20 control
      subjects. SPEM was significantly correlated to Hamilton Rating Scale for
      Depression scores (r = 0.49, P = 0.02) in the depressed patients. Although SPEM
      was transiently disrupted by an acute ECT treatment, it improved during the
      treatment course. This improvement of SPEM quality with clinical recovery
      suggests that SPEM abnormality may be a state marker in severe major depression,
      in contrast to its invariable trait nature in schizophrenia.

PMID- 8148636
TI  - Self-report of symptoms and neuropsychological performance in asymptomatic HIV
      positive individuals.
AB  - This study examined the relationship between subjective complaints and
      neuropsychological performance in 133 HIV-positive asymptomatic and 80 HIV
      negative gay or bisexual men. Presence and duration of self-reported symptoms
      were most strongly related to measures of information processing and reaction
      time. These relationships remained significant when the effect of depression was
      statistically controlled, and no significant relationships were found between CD4
      level and either presence or duration of symptoms. These data suggest that 1)
      depression does not completely account for the relationship between subjective
      complaints and neuropsychological performance and 2) early subjective recognition
      of symptoms may represent a risk factor for subsequent development of
      neurobehavioral abnormalities.

PMID- 8148637
TI  - Use of botulinum toxin injections for spasmodic torticollis of tardive dystonia.
AB  - Because intramuscular injections of type A botulinum toxin (btx) are effective
      for idiopathic spasmodic torticollis, they were administered to 3 patients who
      had neck movements as their only manifestation of tardive dystonia. Each
      improved, with a decrease in involuntary movement and reduction in pain. None had
      either systemic or local side effects. Although expensive, btx treatment is
      recommended for involuntary neck movements of tardive dystonia but not yet for
      the classic buccolingual dyskinesia.

PMID- 8148638
TI  - Predicting long-term outcome in individuals at risk for Alzheimer's disease with
      the Dementia Rating Scale.
AB  - The Dementia Rating Scale, previously shown to be sensitive to dementia
      progression, was used to differentiate among normal control subjects, patients
      with Alzheimer's disease (AD), and those judged to be at risk for AD on the basis
      of subclinical memory impairment. The memory scale of the Dementia Rating Scale
      predicted with 93% accuracy which at-risk individuals would develop AD at 4- to 6
      year follow-up.

PMID- 8148639
TI  - DSM-IV: proposed criteria for postconcussive disorder.

PMID- 8148640
TI  - DSM-IV: mild neurocognitive disorder.

PMID- 8148641
TI  - EXIT, QED, and DSM-IV: regional syndromes.

PMID- 8148642
TI  - EXIT, QED, and DSM-IV: very early Alzheimer's disease.

PMID- 8148643
TI  - Abuse of formaldehyde-laced marijuana may cause dysmnesia.

PMID- 8148644
TI  - Treatment of depersonalization disorder and associated depression with
      electroconvulsive therapy.

PMID- 8148645
TI  - ENOD12, an early nodulin gene, is not required for nodule formation and efficient
      nitrogen fixation in alfalfa.
AB  - To demonstrate the importance of an extensively studied early nodulin gene ENOD12
      in symbiotic nodule development, plants of different Medicago sativa subspecies
      were tested for the presence or absence of ENOD12 alleles. In M. s. ssp coerulea
      w2 (Mcw2), two ENOD12 genes were detected, whereas in M. s. ssp quasifalcata k93
      (Mqk93) only one gene was present. In both plants, the ENOD12 genes were
      expressed in nodules induced by Rhizobium meliloti. The nucleotide sequence of
      the ENOD12 genes showed that the two Mcw2-specific genes were similar to the
      ENOD12A and ENOD12B genes of the tetraploid M. s. ssp sativa. ENOD12 from Mqk93
      was similar to the corresponding gene found in M. truncatula. From the aligned
      ENOD12 sequences, an evolutionary tree was constructed. Genetic analysis of the
      progenies of a cross between Mqk93 and Mcw2 showed that several offspring in F1
      carried a null allele originating from Mcw2, and among the F2 progenies, plants
      with the null allele only lacking the ENOD12 gene appeared. Surprisingly, the
      ENOD12-deficient plants were similar to their wild-type parents in viability,
      nodule development, nodule structure, and nitrogen fixation efficiency.
      Therefore, we concluded that in Medicago the ENOD12 gene is not required for
      symbiotic nitrogen fixation. Furthermore, we proposed that the heterozygous
      nature of these legumes can be exploited for the identification of mutated
      alleles of other known nodulin genes; this will permit the construction of plant
      mutants deficient in these genes.

PMID- 8148646
TI  - Isolation of uvh1, an Arabidopsis mutant hypersensitive to ultraviolet light and
      ionizing radiation.
AB  - A genetic screen for mutants of Arabidopsis that are hypersensitive to UV light
      was developed and used to isolate a new mutant designated uvh1. UV
      hypersensitivity in uvh1 was due to a single recessive trait that is probably
      located on chromosome 3. Although isolated as hypersensitive to an acute exposure
      to UV-C light, uvh1 was also hypersensitive to UV-B wavelengths, which are
      present in sunlight that reaches the earth's surface. UV-B damage to both wild
      type and uvh1 plants could be significantly reduced by subsequent exposure of UV
      irradiated plants to photoreactivating light, showing that photoreactivation of
      UV-B damage is important for plant viability and that uvh1 plants are not
      defective in photoreactivation. A new assay for DNA damage, the Dral assay, was
      developed and used to show that exposure of wild-type and uvh1 plants to a given
      dose of UV light induces the same amount of damage in chloroplast and nuclear
      DNA. Thus, uvh1 is not defective in a UV protective mechanism. uvh1 plants were
      also found to be hypersensitive to ionizing radiation. These results suggest that
      uvh1 is defective in a repair or tolerance mechanism that normally provides
      plants with resistance to several types of DNA damage.

PMID- 8148647
TI  - The transcriptional activator Opaque2 recognizes two different target sequences
      in the 22-kD-like alpha-prolamin genes.
AB  - The maize Opaque2 (O2) protein is a "leucine zipper" DNA binding factor that
      interacts with the sequence TCCACGTAGA in the promoters of the 22-kD alpha-zein
      genes and activates its transcription. A completely different consensus sequence
      (GATGAPyPuTGPu) identified in b-32, a gene that encodes an abundant albumin that
      is also under control of the O2 locus, can also be bound by the O2 protein. We
      showed that the gene encoding the 22-kD-like alpha-coixin, the alpha-prolamin of
      the maize-related grass Coix, can also be transactivated by the O2 protein. A
      binding assay in vitro and footprint analysis demonstrated that the GACATGTC
      sequence of the alpha-coixin promoter can be recognized and protected by the
      maize O2 protein. Employing transient expression experiments in immature maize
      endosperm and tobacco mesophyll protoplasts, we demonstrated that the O2 protein
      can activate expression of the beta-glucuronidase reporter gene placed under the
      control of the 22-kD-like alpha-coixin promoter. We also demonstrated that a 22
      kD-like alpha-coixin pseudogene promoter is transactivated by the maize O2
      protein.

PMID- 8148648
TI  - A novel cis-acting element in an Arabidopsis gene is involved in responsiveness
      to drought, low-temperature, or high-salt stress.
AB  - Two genes, rd29A and rd29B, which are closely located on the Arabidopsis genome,
      are differentially induced under conditions of dehydration, low temperature, high
      salt, or treatment with exogenous abscisic acid (ABA). It appears that rd29A has
      at least two cis-acting elements, one involved in the ABA-associated response to
      dehydration and the other induced by changes in osmotic potential, and that rd29B
      contains at least one cis-acting element that is involved in ABA-responsive, slow
      induction. We analyzed the rd29A promoter in both transgenic Arabidopsis and
      tobacco and identified a novel cis-acting, dehydration-responsive element (DRE)
      containing 9 bp, TACCGACAT, that is involved in the first rapid response of rd29A
      to conditions of dehydration or high salt. DRE is also involved in the induction
      by low temperature but does not function in the ABA-responsive, slow expression
      of rd29A. Nuclear proteins that specifically bind to DRE were detected in
      Arabidopsis plants under either high-salt or normal conditions. Different cis
      acting elements seem to function in the two-step induction of rd29A and in the
      slow induction of rd29B under conditions of dehydration, high salt, or low
      temperature.

PMID- 8148649
TI  - PF1: an A-T hook-containing DNA binding protein from rice that interacts with a
      functionally defined d(AT)-rich element in the oat phytochrome A3 gene promoter.
AB  - Phytochrome-imposed down-regulation of the expression of its own phytochrome A
      gene (PHYA) is one of the fastest light-induced effects on transcription reported
      in plants to date. Functional analysis of the oat PHYA3 promoter in a
      transfection assay has revealed two positive elements, PE1 and PE3, that function
      synergistically to support high levels of transcription in the absence of light.
      We have isolated a rice cDNA clone (pR4) encoding a DNA binding protein that
      binds to the AT-rich PE1 element. We tested the selectivity of the pR4-encoded
      DNA binding activity using linker substitution mutations of PE1 that are known to
      disrupt positive expression supported by the PHYA3 promoter in vivo. Binding to
      these linker substitution mutants was one to two orders of magnitude less than to
      the native PE1 element. Because this is the behavior expected of positive factor
      1 (PF1), the presumptive nuclear transcription factor that acts in trans at the
      PE1 element in vivo, the data support the conclusion that the protein encoded by
      pR4 is in fact rice PF1. The PF1 polypeptide encoded by pR4 is 213 amino acids
      long and contains four repeats of the A-T hook DNA binding motif found in high
      mobility group I-Y (HMGI-Y) proteins. In addition, PF1 contains an 11-amino acid
      long hydrophobic region characteristic of HMG I proteins, its N-terminal region
      shows strong similarities to a pea H1 histone sequence and a short peptide
      sequence from wheat HMGa, and it shows a high degree of similarity along its
      entire length to the HMG Y-like protein encoded by a soybean cDNA, SB16. In vitro
      footprinting and quantitative gel shift analyses showed that PF1 binds
      preferentially to the PE1 element but also at lower affinity to two other AT-rich
      regions upstream of PE1. This feature is consistent with the binding
      characteristics of HMG I-Y proteins that are known to bind to most runs of six or
      more AT base pairs. Taken together, the properties of PF1 suggest that it belongs
      to a newly described family of nuclear proteins containing both histone H1
      domains and A-T hook DNA binding domains.

PMID- 8148650
TI  - gamma-Tubulin in Arabidopsis: gene sequence, immunoblot, and immunofluorescence
      studies.
AB  - gamma-Tubulin is a protein associated with microtubule (Mt)-organizing centers in
      a variety of eukaryotic cells. Unfortunately, little is known about such centers
      in plants. Genomic and partial cDNA clones encoding two gamma-tubulins of
      Arabidopsis were isolated and sequenced. Comparisons of genomic and cDNA
      sequences showed that both genes, TubG1 and TubG2, contain nine introns at
      conserved locations. The sequences of the two genes both predict proteins
      containing 474 amino acids, with molecular masses of 53,250 and 53,280 D,
      respectively. The predicted gamma 1- and gamma 2-tubulins exhibit 98% amino acid
      identity with each other and approximately 70% amino acid identity with the gamma
      tubulins of animals and fungi. RNA gel blot results demonstrated that both genes
      are transcribed in suspension culture cells, seedlings, and roots and flowers of
      mature plants. Immunoblots of Arabidopsis proteins using an antibody specific to
      a conserved peptide of gamma-tubulin showed a major cross-reacting polypeptide
      with an M(r) of 58,000. The same antibody stained all Mt arrays in tissue and
      suspension culture cells of this species. Binding was inhibited by the homologous
      oligopeptide in the gamma-tubulins predicted by the two Arabidopsis gene
      sequences. Antibody staining avoided the plus ends of Mts at the kinetochores and
      cell plate, but unlike the case in animal cells, seemed to be localized over
      broad stretches of the kinetochore fibers and phragmoplast toward the minus ends.
      We concluded that at least two gamma-tubulin protein homologs are present in
      Arabidopsis and that at least one of them is localized along Mt arrays. Its
      distribution is correlated with and may help explain unique characteristics of Mt
      organization in plants.

PMID- 8148651
TI  - Ruffled feathers.

PMID- 8148652
TI  - Nutrition in pediatric primary care: assessment and common problems.
AB  - As health promotion and disease prevention gain prominence, nutritional
      assessment and intervention become important tools for the NP. The nutritional
      needs of the growing child and adolescent are explored, with a discussion about
      common nutritional deficits seen in the pediatric population.

PMID- 8148653
TI  - Leslie de la Flor: putting nutrition into practice. Interview by Karna Bramble.

PMID- 8148654
TI  - Nutritional management of common gastrointestinal problems.
AB  - Nutritional management plays a vital role in many gastrointestinal problems
      commonly seen in primary care. Irritable bowel syndrome, lactose intolerance, and
      celiac sprue are three problems that are best managed by dietary changes. To
      achieve positive outcomes, NPs must know the latest nutritional interventions and
      provide their patients with counseling and education to support these dietary
      changes. Elements of high fiber, lactose-free, and gluten-free diets are
      discussed in this article.

PMID- 8148655
TI  - Obesity: assessment and intervention for primary care practice.
AB  - The 1976-1980 National Health and Nutrition Examination Survey revealed that an
      estimated 34 million adults (26%) between the ages of 20 and 75 are obese. The
      health implications of obesity are well known and contribute to the increased
      morbidity and early mortality in those who are affected. As a result, obesity has
      become a public health concern that has been targeted as a national health
      objective in Healthy People 2000. The overall health objective, related to the
      problem of overweight in adults, is to reduce the prevalence from 26% to < 20%.

PMID- 8148656
TI  - Eating disorders: a women's health problem in primary care.
AB  - Eating disorders pose a significant risk to the health and psychological well
      being of adolescent girls and adult women, yet a sizeable number of health care
      practitioners do not routinely assess for eating disorders. This paper provides
      an overview of what is currently understood about the nature and assessment of
      eating disorders. Diagnostic features, psychiatric comorbidity, and medical
      complications of anorexia nervosa, bulimia nervosa, and binge eating disorder are
      discussed. We suggest ways that health care providers can incorporate assessment
      for eating disorders and referral for treatment into their routine clinical care
      practices.

PMID- 8148657
TI  - Overview of malpractice insurance.

PMID- 8148658
TI  - Nutritional assessment of the elderly in the ambulatory care setting.
AB  - Malnutrition is a major risk for morbidity and mortality among elderly hospital
      and nursing home patients. Moreover, prevalence of malnutrition or inadequate
      nutrition among the elderly is quite high with 10% to 51% of community-residing
      elderly, 20% to 60% of hospitalized elderly patients, and up to 85% of nursing
      home patients showing significant nutritional deficits. Malnutrition in the
      elderly is a multifactorial problem involving physical, physiological,
      psychosocial, and economic factors. Because of the many factors that can
      contribute to inadequate nutrition in the elderly, the clinician needs to assess
      the elderly individual's physical function, cognition, mood, and alcohol use,
      socialization and living arrangements, finances, and medications as part of the
      routine nutrition assessment. Accurate identification of the underlying problems
      is essential. Interventions are aimed at reducing or alleviating risk factors for
      inadequate nutrition or at maintaining or promoting nutritional status. Thus,
      nutrition interventions cover a wide range of activities and can be provided by
      various social and health professionals. This article provides an overview of the
      common factors affecting the elderly's nutritional status, recommended assessment
      techniques, and intervention strategies.

PMID- 8148659
TI  - Assessing nutrition education in clients with weak literacy skills.
AB  - NPs perform a significant role in providing nutrition education in the primary
      care setting. In particular, for those clients with weak literacy skills, NPs
      coordinate and collaborate efforts among other health care professionals to help
      identify and manage nutritional problems. Various strategies applicable to a
      primary care setting are presented.

PMID- 8148660
TI  - Breast cancer and benign breast disease in men.

PMID- 8148661
TI  - Food fights: the struggle to lose weight.

PMID- 8148662
TI  - Development of bone mass and bone density of the spine and femoral neck--a
      prospective study of 65 children and adolescents.
AB  - The bone mineral density (BMD, g/cm2) of the lumbar spine (L2-L4) and femoral
      neck was measured twice with a 1-year interval by dual energy X-ray
      absorptiometry (DEXA) in 65 healthy children and adolescents aged 7-20 years. In
      addition, the BMD values were corrected for the size of bones to obtain the bone
      volumetric density (BMDvol, g/cm3) using a method developed previously. The
      annual increases of BMD and BMDvol in both spine and femoral neck were most
      marked in females at the time of menarche (during the age of 11-13 years), and in
      males between the ages of 13 and 17 years. The males showed significantly higher
      values in their mean annual increment rates of femoral bone mineral content (BMC)
      and femoral neck width, whereas no differences in spinal parameters were found.
      The acquisition of bone mass and bone density stopped or markedly diminished
      before the age of 20 years, supporting the theory that the major portion of the
      peak bone mass is attained in late adolescence. We could not find any significant
      relationship between the increment rate of bone density, and physical activity or
      calcium intake. This study emphasizes the significant effect of puberty and
      genetic factors on the development of bone mass and density.

PMID- 8148663
TI  - Serum ionized calcium, parathyroid hormone and related variables: effect of age
      and sex.
AB  - This study was carried out in order to determine interrelationships of age and
      sex on parameters within the parathyroid endocrine system in healthy men and
      women. One hundred and fifteen normal subjects (70 females and 45 males)
      subdivided into three groups aged 25-35, 45-55 and 65-75 years were studied.
      Female subjects aged between 45 and 55 were further subdivided into two age
      matched groups in relation to gonadal functional status. Serum intact parathyroid
      hormone (PTH) concentrations were measured using a two-site immunoradiometric
      assay. We found that there was a significant decrease of serum ionized calcium
      with ageing only in men (r = -0.666, P < 0.001) and a significant increase of
      serum PTH with age in both men (r = 0.488, P < 0.001) and women (r = 0.279, P <
      0.019). A significant inverse correlation was found between serum ionized calcium
      and PTH in male subjects (r = -0.661, P < 0.001) and in fertile females (r = 
      0.353, P < 0.037) but not in postmenopausal women or in the entire female
      population. Furthermore, we found a significant decline of serum phosphate (r = 
      0.484, P < 0.001) and TmP/GFR (r = -0.492, P < 0.001) with advancing age in men,
      but not in women. We believe that the decrease of serum ionized calcium, as a
      likely consequence of the physiological reduction of intestinal calcium
      absorption, is the pivotal factor responsible for the increased PTH levels we
      observed with advancing age. The phenomenon is clear in men and in premenopausal
      women, but is masked in the female sex at menopause by the effects of a shortage
      of oestrogen on the calcium-phosphorus metabolism. These may also be responsible
      for the differences observed between the two sexes as far as phosphate metabolism
      is concerned. In conclusion, this study has, for the first time, taken
      relationships between serum ionized calcium and PTH, over a wide age range, into
      consideration. The results obtained show a marked difference of serum ionized
      calcium values between sexes with ageing, while serum parathyroid hormone levels
      increase in both men and women. Important differences also exist, as far as
      phosphate metabolism is concerned, between males and females.

PMID- 8148664
TI  - Bone mineral content of two populations of Chinese children with different
      calcium intakes.
AB  - Bone mineral content (BMC) of 5-year-old Chinese children (115 children in
      Jiangmen, China and 128 children in Hong Kong) was evaluated by single-photon
      absorptiometry at the distal 1/3 radius. The mean (S.D.) calcium intakes of
      children of Jiangmen and Hong Kong were 244 (46) and 542 (332) mg/day,
      respectively. The mean BMC, weight and height of Jiangmen children were
      significantly less than Hong Kong children by 14%, 10% and 4%, respectively (P <
      0.001). Multiple regression analysis showed that 62% of the variance in BMC was
      explained by bone width (BW), weight and regional location (P < 0.0001). A
      regional difference in BMC of 0.0303 g/cm (P < 0.0001) still remained after
      adjusting for BW and weight by multiple regression analysis. When comparing sub
      groups of children in the two regions with comparable low current calcium intake
      at 5 years, the BMC of Jiangmen children was still significantly lower than Hong
      Kong children even when potential confounders were adjusted (P < 0.003). The
      study suggests that the regional discrepancy in BMC might be explained by long
      term habitual calcium intake and physical activity.

PMID- 8148665
TI  - 1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from
      patients with postmenopausal osteoporosis.
AB  - A decrease in intestinal calcium absorption, in spite of normal serum calcitriol
      levels, has been reported in postmenopausal osteoporotic women, raising the
      possibility of an intestinal resistance to the hormone. The mechanism responsible
      for it could lie at the receptor or postreceptor level. Intestinal receptors are
      difficult to study on clinical settings, but calcitriol receptors have been found
      in peripheral blood mononuclear cells (PBMC). We have studied the PBMC calcitriol
      receptors by means of Scatchard analysis in 11 postmenopausal osteoporotic women
      without any treatment and in 12 normal postmenopausal women of similar age. No
      differences were found in the dissociation constant (Kd) or the concentration of
      binding sites (Nmax) (Kd in patients: 0.90 +/- 0.75 x 10(-10) M; Kd in controls:
      0.85 +/- 0.40 x 10(-10) M; Nmax in patients: 2.4 +/- 1.2 fmol/10(7) cells; Nmax
      in controls: 2.1 +/- 0.6 fmol/10(7) cells), supporting the contention that the
      disorder responsible for the resistance to calcitriol in postmenopausal
      osteoporotic women is located at the postreceptor level. In addition, our study
      included five postmenopausal osteoporotic women treated with calcitriol (0.5
      microgram/day). The number of calcitriol receptors was increased in this group
      (Nmax: 3.9 +/- 2.0 fmol/10(7) cells vs. 2.1 +/- 0.6 fmol/10(7) cells; P = 0.02).

PMID- 8148666
TI  - Direct evidence of a parathyroid related protein gradient between the mother and
      the newborn in humans.
AB  - Umbilical cord plasma has increased parathormone (PTH)-like bioactivity in
      comparison with that in maternal plasma, but suppressed PTH levels. Previous
      attempts to detect elevated levels of PTHrP(1-34) in the umbilical cord were
      unsuccessful, whereas PTHrP was detected by immunohistochemistry in both fetal
      parathyroid glands and placental membranes. At the time of delivery, plasma
      samples were drawn simultaneously from 47 normal mothers (mean age, 26 years) and
      from the umbilical cord of 25 female and 22 male newborns and assessed for
      calcium adjusted for albumin, magnesium, creatinine, intact PTH and PTHrP. PTHrP
      was measured using a new 2-site immunoradiometric assay recognizing separately 1
      40 and 60-72 residues with a sensitivity of 0.3 pmol/l. Mean (+/- S.D.) plasma
      calcium values were 2.35 +/- 0.10 in the mothers versus 2.63 +/- 0.12 mmol/l in
      the newborns (P < 0.001). PTH values were significantly higher in the mothers, as
      expected (22.3 +/- 14.8 vs. 6.2 +/- 0.9 pg/ml). In contrast, PTHrP values were
      significantly higher in the newborns (1.50 +/- 0.39 versus 0.84 +/- 0.28 pmol/l,
      P < 0.001). Only 1/47 mother had a PTHrP level higher than her child (0.9 vs. 0.8
      pmol/l). Only 10/47 mothers had PTHrP higher than 1 pmol/l whereas only 1/47
      newborn had a value below 1 pmol/l. There was no correlation between Ca and PTHrP
      in either group. Serum creatinine values were all within the normal range. Serum
      magnesium levels were not different between the mothers and the
      children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148667
TI  - Ipriflavone: pharmacological properties and usefulness in postmenopausal
      osteoporosis.
AB  - Ipriflavone (IP) is an isoflavone derivative available in several countries for
      investigational and/or therapeutic use. Inhibition of bone resorption was
      demonstrated in several models, both in vitro and in vivo for IP and its
      metabolites. Their mechanisms of action on bone are not yet fully elucidated but
      some of them are widely accepted. IP does not possess, per se, any estrogenic
      activity. It appears that IP-related inhibition of bone resorption might be
      mediated by an indirect effect on osteoclast and related to an inhibition of
      recruitment and/or differentiation of pre-osteoclast, maybe through a modulation
      of osteoblast response to PTH. Clinical studies in Paget's disease of bone or
      primary hyperparathyroidism have confirmed preferential inhibition of bone
      resorption suggesting a clinical interest in postmenopausal osteoporosis.
      Preliminary (1 year) results of double blind placebo controlled studies designed
      in postmenopausal and senile osteoporosis confirm a reduction in bone turnover
      rate in patients treated with 600 mg/day of IP, resulting in a significant bone
      sparing effect both at lumbar and radial levels. All clinical and pharmacological
      trials confirm a very good tolerance of IP with a frequency of adverse reactions
      equal to that observed during administration of a placebo. Providing ongoing
      studies will confirm the actual promising preliminary results, IP seems a very
      interesting new non hormonal approach for prevention and treatment of
      postmenopausal and senile osteoporosis.

PMID- 8148668
TI  - Bone histomorphometry and serum concentrations of intact parathyroid hormone
      (PTH(1-84)) in patients with primary hyperparathyroidism.
AB  - The consequences of bone disease in primary hyperparathyroidism (PHPT) are still
      a matter of discussion. We studied transiliac bone biopsies of 24 patients (9 men
      and 15 women) with mild to moderate PHPT, proven by surgery. Histomorphometric
      data were compared with control values obtained from autopsy bone samples. The
      biopsies of the PHPT patients were characterized by increased trabecular bone
      volume (P < 0.01) and surface (P < 0.02), increased osteoid volume and increased
      osteoid and resorption surfaces (P < 0.001). Cortical porosity showed a non
      significant increase in the PHPT patients. In the patients the fasting serum
      concentrations of parathyroid hormone (PTH(1-84)) correlated positively with
      cortical porosity (r = 0.50, P = 0.02), osteoid volume (r = 0.40, P = 0.05),
      osteoid surface (r = 0.50, P = 0.01), and eroded surface (r = 0.59, P < 0.01). It
      is concluded that moderate PHPT is associated with preservation of trabecular
      bone, whereas cortical bone may be lost in these patients. Cortical porosity and
      the parameters of bone turnover correlate well with the fasting serum PTH(1-84)
      concentration.

PMID- 8148669
TI  - Apparent velocity of ultrasound (AVU) at the patella in comparison to bone
      mineral density at the lumbar spine in normal males and females.
AB  - It has been reported that apparent velocity of ultrasound (AVU) at the patella
      discriminates as well between osteoporotic and normal subjects as measurement of
      bone mineral density (BMD) using dual photon absorptiometry. To investigate the
      relationship between AVU and peak bone mass, we compared AVU (Signet, Osteo
      Technology, Framingham, MA) at the patella and BMD (QDR 1000, Hologic, Waltham,
      MA) at the lumbar spine in a large sample of healthy males and females. The study
      population consisted of 153 males (aged 20-60 years) and 129 premenopausal
      females (aged 20-52 years). Vertebral BMD showed no significant difference
      between males and females (1.03 +/- 0.16 g/cm2 for males vs. 1.07 +/- 0.14 g/cm2
      for females, NS), while AVU values were significantly higher in males compared
      with females (1967 +/- 64 m/s vs. 1938 +/- 76 m/s, P < 0.05). In men there was a
      significant decrease in BMD with aging (r = -0.27, P < 0.05), in premenopausal
      females we found no age-related change in BMD. Similarly in males AVU decreased
      significantly with age (r = -0.2, P < 0.05), whereas in females AVU values showed
      relative stability over the age range. There was a significant correlation
      between AVU and BMD (r = 0.36 for males, r = 0.34 for females, P < 0.05). Our
      study demonstrates only a weak correlation between AVU at that patella and BMD at
      the lumbar spine, supporting the view that AVU not only reflects bone quantity
      but possibly also qualitative properties of bone structure. The sex difference in
      AVU but not in BMD suggests that the trabecular bone at the patella differs
      significantly from axial trabecular bone. The identical peak BMD at the lumbar
      spine for young males and females underscores the importance of the menopause for
      later manifestation of vertebral fractures.

PMID- 8148670
TI  - Acute effect and mechanism of action of prolactin on the in situ passive calcium
      absorption in rat.
AB  - Acute effect of prolactin (PRL) given intraperitoneally 1 h before on calcium
      fluxes was studied in 6 in situ intestinal segments from weaned, sexually mature
      and aged rats. In mature rats, PRL increased net passive calcium absorption in
      jejunum and cecum by 64% and 38%, respectively, by enhancing lumen-to-plasma
      calcium flux (CaL-P) in the jejunum and by reducing plasma-to-lumen flux (CaP-L)
      in the cecum. Since PRL-enhanced both CaL-P and CaP-L in the ileum, net calcium
      absorption did not change. In weaned rats, PRL significantly increased CaL-P in
      the jejunum but not in the ileum. However, the increase in net absorption was not
      significant. In contrast, effect of PRL was not seen in aged rats. By
      demonstrating an absence of PRL action on jejunal calcium fluxes when sodium-free
      test solution was used, we reconfirmed the sodium-dependent PRL action on passive
      calcium absorption. The PRL-induced parallel increase in the lumen-to-plasma
      transport of 45Ca and [3H]mannitol indicated that PRL action was to increase the
      paracellular transport of calcium.

PMID- 8148671
TI  - Estrogen modulates the mRNA levels for cancellous bone protein of ovariectomized
      rats.
AB  - This study was undertaken to examine the effects of ovariectomy and 17 beta
      estradiol (E2) on the gene expression of type 1 collagen, osteocalcin and the
      protooncogen, c-myc, in cancellous bone. Female Sprague-Dawley rats, aged 95
      days, were divided into 4 groups. Group 1 was sham operated and Groups 2-4 were
      ovariectomized. Groups 3 and 4 received daily injections of 160 ng and 1600 ng
      E2/kg body weight, respectively. Groups 1 and 2 received the solvent vehicle. All
      animals were sacrificed after 14 days. The femurs were dissected out and
      cancellous bone scraped from the distal metaphysis. RNA was isolated from the
      cancellous bone, immobilized on filters or size-fractionated by agarose gel
      electrophoresis and adsorbed on filters which were then hybridized with specific
      cDNA probes. Ovariectomy resulted in a significant increase in the mRNAs of type
      1 collagen, osteocalcin and c-myc. The increase was suppressed in animals that
      received 17 beta-estradiol injections. In addition, ovariectomy caused the
      expected decrease in cancellous bone in the proximal tibia and increased
      osteoclast and osteoblast numbers. The ovariectomy-induced changes were prevented
      by 17 beta-estradiol administration. These findings suggest that the lack of
      ovarian hormones shortly after ovariectomy up-regulates and estrogen
      administration down-regulates the expression of important cancellous bone matrix
      proteins as well as the protooncogen, c-myc.

PMID- 8148672
TI  - Immune cell defects affect bone remodelling in osteopetrotic op/op mice.
AB  - The aim of the present work was to further characterize immunological defects in
      osteopetrosis. The op/op mutant mouse is of particular interest since a marrow
      cavity develops spontaneously in older animals. The interleukin production (IL-1,
      IL-2, IL-3, IL-4, IL-6), the presence of macrophage differentiation antigens and
      the evolution of the bone lesions were studied in osteopetrotic and normal mice.
      Low levels of IL-1, IL-3 and IL-4 were observed at the age of 6 weeks in the
      op/op mice. However, at 22 weeks of age, the level of IL-1 and IL-4 returned to
      normal value in these op/op mice whereas the level of IL-3 remained partially
      decreased at the same age. Furthermore, macrophage expression of MAC-2 antigen,
      reduced at 12 weeks of age was found to be normal 10 weeks later. These
      immunological defects and their recovery seems to be concomitant with the healing
      of the bone lesions.

PMID- 8148673
TI  - Maintenance of bone mass by physical exercise after discontinuation of
      intermittent hPTH(1-34) administration.
AB  - Human PTH(1-34) has been recognized for its marked anabolic effect on bone, but
      that effect has been reported to be lost after cessation of PTH treatment. The
      objective of this study was to determine the fate of hPTH-stimulated bone and
      whether this anabolic effect of PTH could be maintained by daily exercise. Eleven
      week-old Sprague-Dawley rats were ovariectomized (OVX) and human PTH(1-34) (30
      micrograms/kg) was injected subcutaneously three times per week for 12 weeks
      beginning one week after surgery. After the cessation of PTH treatment, treadmill
      exercises were performed for 8 weeks (15.7 m/min, 1 h/day, 5 days/week). The
      results of histomorphometric assessment in the proximal tibial metaphysis
      demonstrated that hPTH treatment partially prevented OVX-induced cancellous bone
      loss. Eight weeks following the cessation of PTH treatment, PTH-stimulated bone
      mass went back to the OVX control level. Daily exercise did maintain PTH
      stimulated bone mass; however, this exercise did not increase the bone mass in
      PTH-untreated OVX rats.

PMID- 8148674
TI  - Asthma: guided self management.

PMID- 8148675
TI  - Peak flow meters: a problem of scale.

PMID- 8148676
TI  - Non-heart beating donors as a source of kidneys.

PMID- 8148677
TI  - Homosexuality and mental health services.

PMID- 8148678
TI  - Integrated care for asthma: a clinical, social, and economic evaluation. Grampian
      Asthma Study of Integrated Care (GRASSIC)
AB  - OBJECTIVES: To evaluate integrated care for asthma in clinical, social, and
      economic terms. DESIGN: Pragmatic randomised trial. SETTING: Hospital outpatient
      clinics and general practices throughout the north east of Scotland. PATIENTS:
      712 adults attending hospital outpatient clinics with a diagnosis of asthma
      confirmed by a chest physician and pulmonary function reversibility of at least
      20%. MAIN OUTCOME MEASURES: Use of bronchodilators and inhaled and oral steroids;
      number of general practice consultations and hospital admissions for asthma;
      sleep disturbance and other restrictions on normal activity; psychological
      aspects of health including perceived asthma control; patient satisfaction; and
      financial costs. RESULTS: After one year there were no significant overall
      differences between those patients receiving integrated asthma care and those
      receiving conventional outpatient care for any clinical or psychosocial outcome.
      For pulmonary function, forced expiratory volume was 76% of predicted for
      integrated care patients and 75% for conventional outpatients (95% confidence
      interval for difference -3.6% to 5.0%). Patients who had experienced integrated
      care were more likely to select it as their preferred course of future management
      (75% (251/333) v 62% (207/333) (6% to 20%)); they saved 39.52 pounds a year. This
      was largely because patients in conventional outpatient care consulted their
      general practitioner as many times as those in integrated care, who were not also
      visiting hospital. CONCLUSION: Integrated care for moderately severe asthma
      patients is clinically as effective as conventional outpatient care, cost
      effective, and an attractive management option for patients, general
      practitioners, and hospital consultants.

PMID- 8148679
TI  - Effectiveness of routine self monitoring of peak flow in patients with asthma.
      Grampian Asthma Study of Integrated Care (GRASSIC).
AB  - OBJECTIVE: To evaluate the effectiveness of routine self monitoring of peak flow
      for asthma outpatients. DESIGN: Pragmatic randomised trial. SETTING: Hospital
      outpatient clinics and general practices in north east Scotland. MAIN OUTCOME
      MEASURES: Use of bronchodilators and inhaled and oral steroids; number of general
      practice consultations and hospital admissions for asthma; sleep disturbance and
      other restrictions on normal activity; psychological aspects of health including
      perceived control of asthma. RESULTS: After one year there were no significant
      differences between patients randomised between self monitoring of peak flow and
      conventional monitoring. However, those given a peak flow meter recorded an
      increase in general practice consultations that was nearly significant. Among
      patients whose asthma was judged on entry to be more severe, those allocated to
      self monitoring used more than twice as many oral steroids (2.2; 95% confidence
      interval 1.1 to 4.6). Patients who already possessed a peak flow meter at the
      start of the study recorded higher morbidity over the course of the year than
      those eligible for randomisation. CONCLUSION: Prescribing peak flow meters and
      giving self management guidelines to all asthma patients is unlikely to improve
      mortality or morbidity. Patients whose asthma is severe may benefit from such an
      intervention.

PMID- 8148681
TI  - Response to organ shortage: kidney retrieval programme using non-heart beating
      donors.

PMID- 8148680
TI  - Accuracy of mini peak flow meters in indicating changes in lung function in
      children with asthma.
AB  - OBJECTIVE: To assess whether mini flow meters used to measure peak expiratory
      flow can track changes in lung function and indicate clinically important
      changes. DESIGN: Comparison of measurements with a spirometer and different
      brands of mini flow meter; the meters were allocated to subjects haphazardly.
      SUBJECTS: 12 boys with asthma aged 11 to 17 attending boarding school. MAIN
      OUTCOME MEASURES: Peak expiratory flow measured twice daily for three months with
      a spirometer and at least one of four brands of mini flow meter. RESULTS: The
      relation between changes in lung function measured with the spirometer and those
      measured with the mini flow meters was generally poor. In all, 26 episodes (range
      1-3 in an individual child) of clinically important deterioration in lung
      function were detected from the records obtained with the spirometer. One mini
      flow meter detected six of 19 episodes, one detected six of 15, one detected six
      of 18, and one detected three of 21. CONCLUSIONS: Not only are the absolute
      values of peak expiratory flow obtained with mini flow meters inaccurate but the
      clinical message may also be incorrect. These findings do not imply that home
      monitoring of peak expiratory flow has no place in the management of childhood
      asthma but that the values obtained should be interpreted cautiously.

PMID- 8148682
TI  - Renal grafts from non-heart beating donors.

PMID- 8148683
TI  - Clinical course and prognostic factors in acute low back pain: an inception
      cohort study in primary care practice.
AB  - OBJECTIVE: To describe the natural course of recent acute low back pain in terms
      of both morbidity (pain, disability) and absenteeism from work and to evaluate
      the prognostic factors for these outcomes. DESIGN: Inception cohort study.
      SETTING: Primary care. PATIENTS: 103 patients with acute localised non-specific
      back pain lasting less than 72 hours. MAIN OUTCOME MEASURES: Complete recovery
      (disappearance of both pain and disability) and return to work. RESULTS: 90% of
      patients recovered within two weeks and only two developed chronic low back pain.
      Only 49 of 100 patients for whom data were available had bed rest and 40% of 75
      employed patients lost no time from work. Proportional hazards regression
      analysis showed that previous chronic episodes of low back pain, initial
      disability level, initial pain worse when standing, initial pain worse when
      lying, and compensation status were significantly associated with delayed episode
      recovery. These factors were also related to absenteeism from work. Absenteeism
      from work was also influenced by job satisfaction and gender. CONCLUSIONS: The
      recovery rate from acute low back pain was much higher than reported in other
      studies. Those studies, however, did not investigate groups of patients enrolled
      shortly after the onset of symptoms and often mixed acute low back pain patients
      with patients with exacerbations of chronic pain or sciatica. Several
      sociodemographic and clinical factors were of prognostic value in acute low back
      pain. Factors which influenced the outcome in terms of episode recovery (mainly
      physical severity factors) were only partly predictive of absenteeism from work.
      Time off work and return to work depended more on sociodemographic and job
      related influences.

PMID- 8148684
TI  - Consensus on diagnosis and management of primary antibody deficiencies. Consensus
      Panel for the Diagnosis and Management of Primary Antibody Deficiencies.

PMID- 8148685
TI  - Homophobia among doctors.
AB  - Homophobia creates stress for gay men and women. An interview study of 28
      doctors, 20 gay and eight non-gay, was performed to assess whether homophobia is
      strong among the medical profession, the stress it causes, and whether the advent
      of AIDS and HIV infection has increased the stress. The doctors, recruited by
      word of mouth and by a letter in the medical and gay press, were asked about
      their own attitudes to homosexuality and AIDS. Only one (non-gay) doctor thought
      that there was no prejudice against gay doctors in the medical profession. The
      gay doctors certainly perceived prejudice, which they claimed caused them extra
      stress; the advent of AIDS had increased this stress to an extent. Doctors who
      had not openly declared themselves to be gay feared doing so because of the
      effect on their job prospects, but those who had declared themselves openly
      reported less stress than previously. Homophobia clearly exists within the
      medical profession. Non-gay doctors should use the power of the profession to
      challenge homophobia in the profession and in society. HIV infection could then
      be treated as a purely medical condition; sufferers would receive wider
      understanding and the pressures of extra workload could be more equally shared.

PMID- 8148686
TI  - Myxoedema revealed by simvastatin induced myopathy.

PMID- 8148687
TI  - The scandal of poor medical research. Sloppy use of literature often to blame.

PMID- 8148688
TI  - The scandal of poor medical research. Undergraduates learn the wrong lessons.

PMID- 8148689
TI  - The scandal of poor medical research. Better libraries and more journal clubs
      would help.

PMID- 8148690
TI  - The scandal of poor medical research. Wrong results should be withdrawn.

PMID- 8148691
TI  - Angiotensin converting enzyme inhibitors and asthma.

PMID- 8148692
TI  - Human parvovirus B19. Virus transmissible in blood products.

PMID- 8148693
TI  - Raw eggs in recipes in magazines should go.

PMID- 8148694
TI  - Failure to thrive. Define it carefully.

PMID- 8148695
TI  - Failure to thrive. Persevere with breast feeding.

PMID- 8148696
TI  - Risk factors for Salmonella infection. Loss of gastric acid linked to
      candidiasis.

PMID- 8148697
TI  - Risk factors for Salmonella infection. Risks higher in developing countries.

PMID- 8148698
TI  - Overruling the parents of child patients.

PMID- 8148699
TI  - Immunity to diphtheria in adults in England.

PMID- 8148700
TI  - Funding international family planning.

PMID- 8148701
TI  - Arterial bypass surgery and smokers.

PMID- 8148702
TI  - Misuse of alcohol or drugs by elderly people.

PMID- 8148704
TI  - Recent initiatives by the European Union.

PMID- 8148703
TI  - Policy on drug misuse in Europe.

PMID- 8148705
TI  - Diagnosing the undiagnosed with diabetes.

PMID- 8148706
TI  - Are clinical information systems safe?

PMID- 8148707
TI  - Zidovudine could cut transmission of HIV by mothers.

PMID- 8148708
TI  - Gulf states test foreigners for AIDS.

PMID- 8148709
TI  - Non-invasive detection of malignancy by identification of unusual CD44 gene
      activity in exfoliated cancer cells.
AB  - OBJECTIVE: To investigate non-invasive detection of cancer by testing for unusual
      CD44 gene activity in a clinical sample as an indicator of exfoliated tumour
      cells. DESIGN: Case-control study. SUBJECTS: 44 unselected, consecutive patients
      with bladder cancer and 46 people with no evidence of neoplasia. MAIN OUTCOME
      MEASURE: Presence or absence of large CD44 gene products containing exon 6
      derivatives in urine samples. RESULTS: Novel abnormalities in the pattern of
      expression of this gene, seen specifically in tumour tissue, led to cloning of a
      newly recognised coding region in it (exon 6). This was tested as a probe for
      detection of exfoliated malignant cells in naturally voided urine. CD44 gene
      products extracted from the urine and amplified with polymerase chain reaction
      contained predicted electrophoretic band of 735 base pairs in 40 of the 44
      patients with bladder cancer (sensitivity 91%). Products from 38 of the 46 people
      with no evidence of neoplasia showed no such band (specificity 83%). CONCLUSIONS:
      Unusual activity of the CD44 locus in neoplasia and malignancy is confirmed, and
      techniques for the analysis of such activity can enable non-invasive
      investigation of patients for primary or recurrent bladder cancer or for other
      tumours that shed neoplastic cells into body fluids.

PMID- 8148710
TI  - Management of acute diarrhoea in diabetic patients using oral rehydration
      solutions containing glucose, rice, or glycine.
AB  - OBJECTIVE: To assess the risk of hyperglycaemia with two standard oral
      rehydration solutions that contain carbohydrate compared with a carbohydrate free
      solution during rehydration of diabetic patients with acute diarrhoea. DESIGN:
      Prospective randomised allocation to one of three oral rehydration solutions
      (World Health Organisation (glucose), rice, or glycine) groups after admission to
      hospital with acute diarrhoea. SETTING: Dhaka hospital of the International
      Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 45 diabetic
      patients aged between 15 and 60 who had had diarrhoea for fewer than three days
      on admission. MAIN OUTCOME MEASURES: Fluctuation of blood glucose concentrations
      measured three times a day, daily stool output, and time taken for recovery from
      diarrhoea. RESULTS: There were no significant differences in blood glucose
      concentrations, stool output, and duration of recovery from diarrhoea among the
      three groups. CONCLUSIONS: Oral rehydration solutions containing glucose, rice
      powder, or glycine can be safely administered to diabetic patients with acute
      diarrhoea and some dehydration.

PMID- 8148711
TI  - The outcome of targeting community mental health services: evidence from the West
      Lambeth schizophrenia cohort.
AB  - OBJECTIVES: To report outcome of targeting community mental health services to
      people with schizophrenia in an inner London district who had been shown, one
      year after discharge, to have high levels of psychotic symptomatology and social
      disability but very low levels of supported housing and structured day activity.
      DESIGN: Repeat interview survey of symptoms, disability, and receipt of care four
      years after index discharge. SETTING: Inner London health district with
      considerable social deprivation and a mental hospital in the process of closure.
      SUBJECTS: 51 patients originally aged 20-65 years who satisfied the research
      diagnostic criteria for schizophrenia. MAIN OUTCOME MEASURES: Contact with
      services during the three months before interview, levels of symptoms (from
      present state examination), global social disability rating. RESULTS: 65% (33/51)
      of the study group had been readmitted at least once in the three years between
      surveys. Recent contacts with community psychiatric nurses and rates of hospital
      admission increased (8 at one year v 24 at four years, p < 0.01; 5 v 13, p <
      0.06). Conversely, fewer patients were in contact with social workers (17 v 7, p
      < 0.03). Proportions in supported housing, day care, or sheltered work did not
      change. Unemployment rates remained very high. A considerable reduction (almost a
      halving) in psychiatric symptoms was observed, but there was no significant
      change in mean levels of social disability. CONCLUSIONS: The policy of targeting
      the long term mentally ill resulted in significant increases in professional
      psychiatric input to the cohort but failed to improve access to social workers or
      suitable accommodation. Improvements in social functioning did not follow from
      reductions in the proportions of patients with psychotic mental states. Social
      interventions are likely to be crucial to achieving the Health of the Nation
      target of improving social functioning for the seriously mentally ill, as
      improving mental state seems in itself to be insufficient.

PMID- 8148712
TI  - Nocturnal blood pressure in normotensive subjects and those with white coat,
      primary, and secondary hypertension.
AB  - OBJECTIVE: To compare the mean nocturnal blood pressure of patients with various
      forms of renal and endocrine hypertension with that in patients with primary and
      white coat hypertension, and normal blood pressure. DESIGN: Ambulatory monitoring
      of blood pressure over 24 hours in a prospective study. SETTING: Two German
      centres for outpatients with hypertension and kidney diseases. SUBJECTS: 176
      normotensive subjects, 490 patients with primary hypertension including mild and
      severe forms, 42 with white coat hypertension, 208 patients with renal and
      renovascular hypertension, 43 with hypertension and endocrine disorders, and
      three with coarctation of the aorta. MAIN OUTCOME MEASURES: Fall in nocturnal
      blood pressure. RESULTS: Blood pressure in normotensive subjects fell by a mean
      of 14 mm Hg (11%) systolic and 13 mm Hg (17%) diastolic overnight (2200 to 0600).
      The falls in patients with primary and white coat hypertension were not
      significantly different. In all patients with renal and renovascular
      hypertension, however, the fall was significantly reduced (range of fall from 3/3
      mm Hg to 7/9 mm Hg). In patients with hypertension and endocrine disorders the
      pattern of night time blood pressure was not uniform: patients with
      hyperthyroidism, primary hyperaldosteronism, and Cushing's syndrome had
      significantly smaller reductions in blood pressure (6/8, 4/7, 3/6 mm Hg,
      respectively). In patients with phaeochromocytoma the mean night time blood
      pressure increased by 4/2 mm Hg. In patients with hypertension, primary
      hyperparathyroidism, and unoperated coarctation of the aorta the falls in blood
      pressure were normal. CONCLUSIONS: In normotensive subjects and those with
      primary hypertension there is usually a reduction in blood pressure at night. In
      all renal forms of secondary hypertension and in most endocrine forms the
      reduction in blood pressure is only a third to a half of normal. Patients with
      primary hyperparathyroidism and unoperated coarctation of the aorta show a normal
      reduction.

PMID- 8148713
TI  - Effect of advertising on awareness of symptoms of diabetes among the general
      public: the British Diabetic Association Study.
AB  - OBJECTIVE: To determine the impact of posters advertising symptoms of diabetes on
      public knowledge of these symptoms. DESIGN: Structured street interviews of
      members of the general public before, at the end of, and 10 weeks after a
      campaign advertising the main symptoms of diabetes. SETTING: Basingstoke and
      Wolverhampton. SUBJECTS: Three samples of 1000 members of the general public were
      interviewed. Samples were selected randomly but stratified to match the local
      population's age (20-75), sex, social class, and racial characteristics. MAIN
      OUTCOME MEASURES: Knowledge of symptoms of diabetes; perceived seriousness of
      diabetes; and induction of anxiety about symptoms in the target population.
      RESULTS: Advertising significantly raised knowledge (without prompting) of
      symptoms: thirst, 245 before v 411 at end of campaign (P < 0.0001) v 341 after (P
      = 0.0012 v before); polyuria, 72 v 101 (P = 0.0211) v 92 (P = 0.5169); lethargy,
      180 v 373 (P < 0.0001) v 298 (P < 0.0001); knowledge of weight loss and visual
      disturbance was unaffected. The number of subjects lacking knowledge of any
      symptoms was reduced from 550 to 388 (P < 0.0001). The perceived seriousness of
      diabetes was unaffected (mean 7.6 in each phase on a scale of 1 (not) to 10
      (very). Before advertising, 449 (45%) claimed to have one or more symptoms of
      diabetes, but this number fell at the end of the campaign (403; P = 0.0419) and
      10 weeks afterwards (278; P < 0.0001). CONCLUSIONS: An advertising campaign
      raised public knowledge of diabetes symptoms without inducing fear of diabetes or
      anxiety about symptoms. Its potential for achieving earlier detection of non
      insulin dependent diabetes should be evaluated.

PMID- 8148714
TI  - Prevalence of HIV infection in patients attending an inner city accident and
      emergency department.

PMID- 8148715
TI  - Measuring prescribing: the shortcomings of the item.
AB  - OBJECTIVES: To assess the validity of the item as a measure of the volume of a
      drug prescribed; and to investigate the possibility that higher quantities per
      item are prescribed for patients who are not exempt from the prescription charge.
      DESIGN: Five substudies. For the first, a frequency distribution was derived of
      the different quantities per item of 10 commonly used drugs prescribed by 20
      randomly selected practices in each of five family health service authority
      areas. For the second, the variation in average quantity per item for the same
      drugs in the same practices was calculated. For the third and fourth, variation
      in average quantity per item for 90 commonly used drugs was calculated for all 90
      family health service authorities and for all 14 regional health authorities in
      England. For the fifth, the average quantity per item for each of the 90 drugs
      was regressed on the percentage of items exempt from the prescription charge, at
      family health service authority level, and the percentage of variation explained
      by the regression found. MAIN OUTCOME MEASURE: Distribution of quantity per item;
      variation in average quantity per item between the practices, between family
      health service authorities, and between regions; and percentage of variation
      between family health service authorities accounted for by exemption from the
      prescription charge. RESULTS: Wide variation was found in the quantities per item
      prescribed by the practices, and in the average quantity per item between
      practices and between family health service authorities. No family health service
      authority was consistently high or low in quantity per item across the 90 drugs.
      Variation in average quantity per item was less at regional than at family health
      service authority level, though still high for many of the drugs. The proportion
      of variation accounted for by exemption from prescription charges ranged from 0%
      to 49% across the 90 drugs. CONCLUSIONS: The item is unsuitable as a measure of
      prescribing volume, even at regional level: a new measure, based on standard
      daily dosages, is needed. The percentage of the variation in quantity per item
      accounted for by exemption is inconsistent, and in over half the 90 drugs it was
      below 20%--therefore it is not a useful predictor.

PMID- 8148716
TI  - Do growth chart centiles need a face lift?
AB  - European height and weight growth charts commonly extend from the 3rd to the 97th
      centile, whereas in North America the extremes are usually the 5th and 95th
      centiles. There is no good reason for the difference, and neither chart is
      particularly useful for screening owing to the high false positive rate
      associated with a cut off based on the lowest centile. The World Health
      Organisation's international growth reference uses cut offs based on standard
      deviation scores rather than centiles, which are more suitable for the extremes
      of growth status seen in the developing world. This chart, however, is
      incompatible with charts based on centiles. Here a unified growth chart is
      proposed: it has nine rather than seven centiles, and they are spaced two thirds
      of a standard deviation score apart rather than the more usual unit spacing. This
      gives a set of curves very like the conventional 3rd to 97th centiles, but with
      additional curves at 2.67 standard deviation below and above the mean (roughly
      the 0.4th and 99.6th centiles). The 0.4th centile is a more practical cut off for
      screening purposes than the 3rd or 5th centile.

PMID- 8148717
TI  - Complicated myocardial infarction.

PMID- 8148718
TI  - The changing scene in general practice in Europe.

PMID- 8148719
TI  - Antiplatelet prophylaxis. Consider the protective effect of blood loss from the
      gut.

PMID- 8148720
TI  - Compliance in screening programmes. High compliance essential in cervical
      screening programme...

PMID- 8148721
TI  - Managing halitosis. Remember the tongue.

PMID- 8148722
TI  - Compliance in screening programmes .... and in breast screening programme.

PMID- 8148723
TI  - Gangliosides and Guillain-Barre syndrome. No causal link.

PMID- 8148724
TI  - Anticoagulation in patients with atrial fibrillation.

PMID- 8148725
TI  - Gangliosides and Guillain-Barre syndrome. Apparent association is a coincidence.

PMID- 8148726
TI  - Variation in caesarean section rates. What difference does it make.

PMID- 8148727
TI  - Variation in caesarean section rate. Maternal mortality higher after caesarean
      section.

PMID- 8148728
TI  - Pertussis immunization and neurological illness.

PMID- 8148729
TI  - Preventing the hand-arm vibration syndrome.

PMID- 8148730
TI  - Sunburn and melanoma.

PMID- 8148731
TI  - Avoidable factors in stroke.

PMID- 8148732
TI  - Confidentiality, contraception and young people.

PMID- 8148733
TI  - Fluoroquinolones in upper respiratory tract infections.

PMID- 8148734
TI  - Tobacco advertising near schools.

PMID- 8148735
TI  - Infant death and consanguineous marriage.

PMID- 8148736
TI  - [Psychological and pediatric psychiatry aspects of development of children
      resulting from medical reproduction treatment of their parents].
AB  - Subject matter are actual case reports dealing with somatic symptoms in child
      development. Related thoughts on child psychiatry and development psychology are
      being discussed with due respect to the understandable reluctance of the parents
      in revealing and reflecting details of the development of child and parents. A
      future goal should be to keep child development under a closer surveillance for a
      longer period of time with special focus on the parent-child and the inter-parent
      relationship.

PMID- 8148737
TI  - [In vitro fertilization--challenge to our awareness of conception and
      reproduction].

PMID- 8148738
TI  - [Ethical aspects of in vitro fertilization from the medical viewpoint].

PMID- 8148739
TI  - [Responsibility of the physician in reproductive medicine].
AB  - The article explores the responsibility of the physician in reproductive medicine
      as a therapist of the couple and the child. It is based on the understanding of
      responsibility as a term with six relations. The article emphasizes that
      responsibility can only be ascribed to the physician with regard to the structure
      of the physicians acting.

PMID- 8148740
TI  - Conversation with Vincent Dole.

PMID- 8148741
TI  - Why do some people recover from alcohol dependence, whereas others continue to
      drink and become worse over time?
AB  - For more than three decades, my colleagues and I have examined factors that help
      people overcome adversity, in particular how personal and treatment factors and
      the broader social context influence recovery from alcoholism. Guided by a
      demanding Guardian Angel, we have formulated conceptual models that raise key
      issues, developed tentative measures of key constructs, and conducted long-term
      naturalistic studies. In an ongoing odyssey of quest and discovery, we have
      identified interrelated factors that are important to predicting outcomes. These
      factors include personal resources and specific aspects of treatment, life
      context, and appraisal and coping. Such basic processes are also broadly relevant
      to remission and recovery from depression and other disorders. The answers to
      each question we have addressed point to more intriguing and complex issues to
      consider before we will grasp the essence of why some people adapt to adversity
      so much better than others do.

PMID- 8148742
TI  - Research in general practice for smokers and excessive drinkers in Australia and
      the UK. I. Interpretation of results.
AB  - This review examines the role of the general practitioner in assisting patients
      to stop smoking and in reducing levels of excessive drinking. After over a decade
      of clinical trials, we discuss what interventions work in general practice and
      interpret the results of clinical trials conducted predominantly in Australia and
      the UK. Studies have generally found a superiority of GPs' brief advice over non
      intervention groups. Very brief GP advice results in smoking abstinence rates
      from 5% to 10%, reduction in alcohol consumption of around 25-35% and reduction
      in proportions of excessive drinkers of around 45%. The greater investment of
      GPs' time and the more comprehensive interventions which include follow up
      usually resulted in higher abstinence rates among smokers from between 20% to
      36%, and reduction in proportions of excessive drinkers of up to 60-70%. The
      contributions of the adjuncts nicotine chewing gum, follow up visits and the
      personalization of health effects are discussed. It is difficult to make
      comparisons between studies and we examine some of the reasons. The predictors of
      successful outcome are presented as they are of particular interest to GPs in
      terms of targeting health promotion activities.

PMID- 8148743
TI  - Research in general practice for smokers and excessive drinkers in Australia and
      the UK. II. Representativeness of the results.
AB  - This paper reviews some of the issues related to the appropriateness of
      generalizing the results from clinical trials which have been conducted in
      general practice for smokers and excessive drinkers. We discuss the
      representativeness of the results related to the method of recruitment of general
      practices and patients to the study populations. We examine methodological issues
      and reasons associated with general practitioners' and patients' non-compliance
      with maintaining the research protocols and intervention requirements which
      relate to the practiceworthiness and the future uptake of interventions. When
      assessing the applicability of interventions to general practice, there are three
      basic research questions which should be looked at quite separately that relate
      to: efficacy, effectiveness and implementation.

PMID- 8148744
TI  - Research in general practice for smokers and excessive drinkers in Australia and
      the UK. III. Dissemination of interventions.
AB  - This article reviews the main methods of dissemination of interventions to
      doctors for the benefit of patients who are smokers and excessive drinkers.
      Firstly, the modes of delivery of interventions are discussed such as: postal
      delivery, face-to-face strategies such as an educational facilitator, courier,
      training workshops, reinforcement contact after training, and teaching in medical
      school. Secondly, we examine GPs' delivery of interventions working in
      association with others such as with: the health visitor, health facilitator,
      practice nurse, and specialist clinic. Thirdly, we discuss the debate about the
      public health impact of GP interventions for smokers, which is about rates of
      recruitment of patients to programs and about the most effective interventions
      that will continue to be used by GPs. Fourthly, doctors underutilize their
      opportunities to identify and intervene with smokers and excessive drinkers and
      we explore many of the barriers to intervention. Finally, there are several new
      initiatives in general practice that require research including: matching GPs to
      specific treatments, comparing the uptake and continued use of different levels
      of interventions, evaluating the most effective ways of delivering interventions
      to GPs, and the training of doctors in the intervention methods.

PMID- 8148745
TI  - Alcoholism--still an inferior disease?

PMID- 8148746
TI  - Mediators and moderators of young adults' drinking.
AB  - Direct effects of modeling and indirect effects of social perception processes
      have been implicated in the acquisition and maintenance of alcohol use. Parental
      and peer drinking behavior (assessed from self-reports), and student perceptions
      about parent and peer drinking (assessed from student estimates of their parents'
      and friends' alcohol use) were examined through surveys of college students,
      their parents, and a same-sex best friend. Results showed that students'
      perceptions about their parents' drinking and parents' self-reported quantity of
      alcohol consumed were significant correlates of students' own drinking.
      Perceptions about their friends' alcohol use were found to mediate the strong
      correlation between student and friend drinking. Perceived similarity to parents,
      but not perceived similarity to their friend, moderated the relation between
      students' alcohol use and their perceptions about the alcohol use of significant
      others. When parents were asked to estimate the alcohol use of their sons,
      daughters, and the average college student, they consistently estimated lower
      consumption for their offspring than for the average student.

PMID- 8148747
TI  - HIV risk-taking behaviour among amphetamine users in Sydney, Australia.
AB  - A survey was undertaken of needle-sharing and sexually risky behaviour among 231
      Australian amphetamine users, half of whom usually injected amphetamine. The
      prevalence of risky needle use and sexual behaviour was similar to that observed
      in recent Australian surveys of opioid injectors. About a third of those who had
      ever injected had shared needles, and the variables that best predicted frequency
      of sharing needles were having an injecting drug user as a partner, having
      experienced symptoms of dependence on amphetamines, and having sought medical
      treatment for an amphetamine related problem. Regular condom use with either
      regular or causal partners was low; only the minority employed in the sex
      industry regularly used condoms. Sexual risk-taking was not related to needle
      sharing or amphetamine use. Although Australian amphetamine and opioid users have
      reduced their risks of transmitting HIV, there remains a substantial minority of
      both types of drug injector who continue to place themselves and others at risk
      by sharing needles and engaging in unsafe sexual behaviour.

PMID- 8148748
TI  - Sex differences in morbidity among respondents classified as alcohol abusers
      and/or dependent: results of a national survey.
AB  - To date, none of the studies on gender differences in physical morbidity have
      focused on persons classified as DSM-III-R alcohol abusers and/or dependent in
      the general population. This Data Note presents data from a nationally
      representative survey on drinking practices and related problems for the purpose
      of examining gender differences in physical morbidity among respondents receiving
      these diagnoses. Results indicated that for certain major sociodemographic
      subgroups of the population, gender differences in morbidity were significant.
      The female-to-male odds ratios of these subgroups generally varied within the
      range of 1.5 and 2.0, reflecting about two times greater odds of experiencing
      morbid conditions for females when compared to males.

PMID- 8148749
TI  - Addiction, reductionism and Aaron's rod.

PMID- 8148750
TI  - Distinctive features of the methadone treatment program of Victoria, Australia.

PMID- 8148751
TI  - Gender differences in needle sharing behaviour patterns.

PMID- 8148752
TI  - Do female injectors under-utilize needle exchanges?

PMID- 8148753
TI  - [Effect of isosorbide dinitrate on pulmonary venous compliance].
AB  - Irreversible poor pulmonary venous compliance (PV comp) could worsened natural
      course of patients (pts) with high pulmonary capillary wedge pressure especially
      pts with mitral stenosis. Nitrates (isosorbide dinitrate-ISDN) possessing venous
      dilating action could increase PV comp in most of pts. The main aim of that study
      was to assess hemodynamic effects of ISDN, in pts with MS, with special emphasis
      on PV com changes. PV comp was estimated according to Hirakawa equation (dV/dp =
      0.4*k2*SV/(v-d) in 35 pts with MS, during preoperative right heart
      catheterisation with VYGON 5155-180 thermodilution catheters during rest and
      effort in supine position (25W). The same protocol was performed after Iso-Mack
      sprawy 3.75 mg. According to the PV comp response to ISDN, pts were divided in
      two groups: good responders (I)-15% and higher increase in PV comp and poor
      responders (II). ISDN increased PV comp in the whole group according to the
      response to ISDN, there were significant differences in stroke volume index (SVI)
      and heart rate (HR). In the group of good responders mean right atrial pressure
      (RA), mean pulmonary artery pressure (PAP), mean pulmonary wedge pressure (PWP)
      decreased significantly with simultaneous slight not significant decrease in SVI
      and not significant increase of HR. In the group of poor responders SVI decreased
      significantly by about 20% with significant increase of HR. In conclusion
      significant decrease in pulmonary pressures (PAP, PWP) in pts with good response
      to ISDN are secondary to the increase of PV comp, while among poor responders the
      same effects are due to diminished flow secondary to the decrease of the systemic
      venous return.

PMID- 8148754
TI  - [Effect of improper pulmonary venous compliance on clinical results of mitral
      valve replacement].
AB  - The pulmonary venous vascular volume and its compliance (PVcomp) are important
      factors influencing filling of the left ventricle. It seems that a poor PVcomp
      effects the value and reversibility of secondary pulmonary hypertension. Basing
      on Hirakawa's method PVcomp (= 0.4'' x SV/V-d) was calculated in 34 patients with
      isolated mitral stenosis (SM). Basing on the mean value of PVcomp the group was
      divided into those with poor (< = 4.3 ml/mmHg) and good (4.4 and more ml/mmHg)
      PVcomp. Prior mitral valve replacement (MVR) the groups did not differ in values
      of PAP, PWP, SVI, PVR assessed at rest. During exercise (25 Watt) in the supine
      position significant higher values of PAP and PWP were observed in patients with
      poor compliance. Six months after MVR the PAP and PWP values normalized in all
      patients. In the patients with the initial good PVcomp values significantly
      higher values of SVI and a decrease in PVR was found. During exercise (25 Watts)
      significantly higher values of PAP and PVR were registered in patients with
      initial poor PVcomp values. Pulmonary venous compliance may be an independent
      factors influencing the clinical outcome of mitral valve replacement 6 months
      after the procedure.

PMID- 8148755
TI  - [Role of pentoxifylline in prevention and treatment of adult respiratory distress
      syndrome].
AB  - Pentoxifylline (3,7-dimethyl-1-/5-oxohexyl)-xanthine (PTXF) is a drug that has
      been demonstrated to improve peripheral vascular circulation. The mechanism of
      this effect is believed to involve the prevention of platelet aggregation,
      reduction of blood viscosity and increase red blood cell flexibility. PTXF has
      been successfully used as a therapeutic agent for intermittent claudication
      secondary to chronic occlusive arterial disease. In the present paper, the
      special attention was paid to the possibility of using PTXF in the treatment of
      ARDS and PTXF mechanisms of action preventing the development of that syndrome
      were reviewed.

PMID- 8148756
TI  - [The effect of pentoxifylline on the degree of lung parenchyma injury after
      papain].
AB  - In the last years pentoxifylline (PTXF) has been successfully used in reducing
      acute injury of the lung parenchyma in ARDS. The authors have studied the effect
      of PTXF on degree of papain induced lung injury. Papain was administered
      intratracheally in a dose of 2 mg, 4 mg, 6 mg in 1 ml of PBS. The effect of
      papain on bronchoalveolar lavage characteristics was also evaluated. Wistar rats
      of both sexes were used in the experiment. The degree of lung destruction,
      reflected by interstitial hemorrhage was assessed by measuring hemoglobin content
      in the fluid of the lavaged lungs. The hemoglobin levels were assessed
      spectrofluorometrically with the use of the 414 nm wave length. A reduction of
      hemoglobin content was seen after PTXF administration only in animals receiving
      the lowest dosage of papain. However in all animals a decrease in the BAL
      neutrophil count was demonstrated. The protective effect of PTXF on pulmonary
      tissue in papain induced injury models and situations leading to development of
      ARDS may suggest a similar pathomechanism in both entities.

PMID- 8148757
TI  - [The influence of n-acetylcysteine on chemiluminescence of granulocytes in
      peripheral blood of patients with chronic bronchitis].
AB  - The effect of NAC on exacerbation of chronic obstructive pulmonary disease (COPD)
      may be due to its mucolytic properties due to the thiol group of NAC and to its
      reducing and antioxidant properties. It has been postulated that NAC may protect
      lung cells from inhaled oxidants or oxidants produced by inflammatory leukocytes
      by increasing intra and extra cellular GSH. The FMLP induced granulocyte
      chemiluminescence (CL) in 6 healthy and 12 patients with COPD was determined.
      Peripheral blood polymorphonuclear leukocytes were incubated with NAC. The
      results obtained show a significant decrease of CL after incubation with NAC in
      both groups. We also found higher CL in healthy subjects than patients with COPD.
      This study showed a significant increase of FVC, FEV1 and a significant decrease
      of granulocyte CL after treatment with oral NAC 200 mg three times daily for 3
      weeks.

PMID- 8148758
TI  - [Pathogenic action of Erwinia herbicola. I. In vitro investigations].
AB  - The effects of antigen and endotoxin of Erwinia herbicola on physiological status
      of alveolar macrophages were studied in vitro. The studies comprised
      determination of the cytotoxicity of antigens + and their effects on superoxide
      anion and interleukin-1 (IL-1) generation by alveolar macrophages. It was found
      that tested agents were cytotoxic for alveolar macrophages in large
      concentrations (from 1000 micrograms/ml. In lower concentrations (1-10
      micrograms/ml) they stimulated the activity of alveolar macrophages, causing
      significant increase in superoxide anion(O2) and IL-1 generation. Superoxide
      anion and IL-1 production may be of importance in pathogenesis of organic dust
      induced lung diseases and our results indicate that agents associated with these
      diseases induced their production.

PMID- 8148759
TI  - [Pathogenic action of Erwinia herbicola. II. In vivo investigations].
AB  - The pulmonary response of guinea pigs to inhalation of antigen and endotoxin of
      Erwinia herbicola was investigated. Pulmonary parameters monitored in this study
      were breathing rate, cellular differential counts from bronchoalveolar lavage
      fluid, superoxide anion and interleukin-1 (IL-1) production by alveolar
      macrophages. Both agents caused an increase in breathing rate; an influx of
      neutrophils, lymphocytes, and red blood cells to the lung; and an enhancement of
      secretion of superoxide anions and IL-1 by pulmonary macrophages. The results
      indicate significant role of extrinsic bacilli Erwinia herbicola in respiratory
      pathology and show new mechanisms of their action.

PMID- 8148760
TI  - [Test of a quick differentiation of selected mycobacteria with pyrolytic gaseous
      chromatography].
AB  - The five mycobacterium strains H37Rv series 363, M. bovis (An5) series 250, M.
      kansasii series 377, M. intracellulare series 364, M. xenopi series 302 and BCG
      series 180291 were tested using pyrolytic gas chromatography method. After
      regeneration of lyophylisate, the strains were incubated using L-J medium in 37
      degrees C for 2 to 6 weeks--the period that was necessary to obtain profuse
      growth. The bacterial mass obtained from the culture was collected in test-tubes
      and pyrolized after autoclave incubation and dry procedure. The CHROM 5 gas
      chromatograph together with FID detector was used for detecting the products of
      pyrolysis. The signal was transmitted from the detector to analog-digital
      converter A/C and registered by IBM PC/XT computer. 12-15 analysis of each strain
      were performed. Chromatograms of strains pyrolysis products were recorded as
      files to the hard disc. This way the standard data base was built. The pyrolysis
      products of tested strains were compared with data base using BAZCHRO program. E.
      coli JC 7623 was employed as a standard for comparison of chromatograms. The
      similarity of chromatograms was presented as percentage. The 85-95% of similarity
      was obtained as a result of comparison of the same Mycobacteria strains.

PMID- 8148761
TI  - [Pulmonary infections in patients with lung cancer during antineoplastic
      therapy].
AB  - 162 pulmonary infection episodes were observed in 94 patients with lung cancer
      undergoing antineoplastic therapy. 80 (40%) episodes occurred during leukopenia.
      Elevation of leucocyte count was seen in 12 episodes only. Elevated body
      temperature was the only sign in 20 episodes, of which in 7 cases microorganisms
      were cultured from the blood. Purulent pulmonary infections were observed in 71
      episodes, in 66 the causative agent was identified. Purulent urinary tract
      infections were observed in 29 episodes, of which in 28 the microorganisms were
      identified. A coexistent pulmonary and urinary tract infection was seen in 13
      cases, of which in all the causative agent was identified. Purulent infections of
      the nasopharyngeal mucosal membranes were observed in 16 cases, while herpes
      zoster in 13. The most often isolated organism in these cases were: Gram negative
      rods (E. coli, Klebsiella sp., Proteus sp., Hemophilus influenzae); less commonly
      Gram positive bacteria were isolated, mainly Staphylococcus aureus. Candida sp.
      was the most common fungus that was isolated from these patients. In four cases
      Candida was isolated from blood.

PMID- 8148762
TI  - [Complications in the respiratory tract from measles].
AB  - In the study and incidence of measles complications in the respiratory tract was
      analyzed in patients hospitalized in the Department of Infectious Diseases CSK
      WAM in 1972-1992 because of measles. In this period the (equal?) epidemiology of
      disease was observed in 1989/1990. In 17% hospitalized patients pharyngitis
      and/or pneumonia were observed as a typical complications of measles. High
      percentage of complications without consequences was probably connected with
      virus mechanism of infection.

PMID- 8148763
TI  - [Epidemic of Pneumocystis carinii infection in infants].
AB  - Epidemic intra-ward infection caused by Pneumocystis carinii was described. 18
      infants and small children were ill from among 21 treated in the infants ward.
      The diagnosis was given on the grounds of cytologic examination of bronchial
      excretion from subglottic region.

PMID- 8148764
TI  - [A case of accessory bronchus].

PMID- 8148765
TI  - [Alveolar phospho-lipo-proteinosis--etiologic, pathogenetic and diagnostic
      problems--presentation of cases].

PMID- 8148766
TI  - [A case of lipid pneumonia].
AB  - The authors discuss the etiology, pathomechanisms, radiological features of lipid
      pneumonia. The role of bronchoalveolar lavage is stressed in determining this
      diagnosis. A case is presented of a patient receiving paraffin oil for chronic
      constipation. The diagnosis was made after identifying the lipid droplets (Sudan
      III stain) in alveolar macrophages sampled by BAL.

PMID- 8148767
TI  - [Osteochondroplastic tracheobronchopathy--relation to rhinitis atrophica and iron
      deficiency].
AB  - Tracheobronchopathia osteochondroplastica (TO) is a rare disease with
      accumulation of bony and cartilaginous nodules in the tracheal and bronchial
      mucosa. In some cases rhinitis atrophica (ozena) has been associated. A case of
      TO coexisting with ozena and iron deficiency anaemia was described.

PMID- 8148768
TI  - [Coexistence of tuberculosis and diabetes. Clinical and treatment aspects].

PMID- 8148769
TI  - [Respiratory infections in patients with immunosuppression].

PMID- 8148770
TI  - [Computed tomography with high resolution in interstitial lung diseases].

PMID- 8148771
TI  - [Viral infections of the respiratory system. I. influenza infections].

PMID- 8148772
TI  - [Viral infections of the respiratory system. II. Immunity against the influenza
      virus].

PMID- 8148773
TI  - [Respiratory disturbances in myasthenia gravis].

PMID- 8148774
TI  - [Nobel prize in the field of physiology and medicine in 1993].

PMID- 8148775
TI  - Insulin resistance: the link between impaired glucose tolerance, body mass index
      and plasma lipids.
AB  - Body mass index defined as weight (Kg)/height (cm2) and plasma lipids (total
      lipids-TL, triglycerides-TG and cholesterol-CH) were determined in 131 patients
      (61 males and 70 females aged between 21 and 63 years) with impaired glucose
      tolerance (IGT) defined according to WHO criteria. Blood glucose (BG) values and
      plasma insulin (PI) levels (radioimmunological assay) were determined during 2
      hours OGTT with samples obtained before and after 1 h and 2 h after the intake of
      75 g glucose. The sum of blood glucose and plasma insulin levels (0 + 1h + 2h)
      were compared in each of the following 5 groups of subjects: A--25 cases with IGT
      but without obesity (BMI: 23.2 +/- 2.6) and hyperlipidaemia (PL: 627 +/- 112; TG:
      102 +/- 109 and CH: 208 +/- 35 mg/dl); B--35 cases with IGT and obesity (BMI:
      31.2 +/- 2.6) but without hyperlipidaemia (PL: 807 +/- 109; TG: 136 +/- 31 and
      CH: 254 +/- 41 mg/dl); C--23 cases with IGT and hyperlipidaemia (PL: 1013 +/-
      217; TG: 214 +/- 85 and CH: 311 +/- 52 mg/dl) but without obesity (BMI: 25.4 +/-
      1.9); D--48 cases with IGT and both obesity (BMI: 30.9 +/- 2.8) and
      hyperlipidaemia (PL: 1457 +/- 155; TG: 597 +/- 188 and CH: 483 +/- 184 mg/dl); a
      control group of 49 cases without IGT, obesity (BMI: 26.2 +/- 1.9) or
      hyperlipidaemia (PL: 726 +/- 99 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148776
TI  - Risk factors and risk determinants for the evolution of the diabetic nephropathy
      in IDDM: a case control study of 108 IDDM patients in the Bucharest Center of
      Diabetes.
AB  - The study included 108 IDDM patients (59 males, 49 females, aged 15-59 years)
      from the Bucharest Diabetic Centre which participated in the EURODIAB
      multicentric study. They were divided into three groups according to the duration
      of diabetes (less than 7 years; 8 to 14 years; more than 15 years) and we have
      made a comparison between the importance of some risk factors, as elevated blood
      pressures, age, elevated levels of the total plasma cholesterol, and glycosylated
      hemoglobin (HbA1C) on the progression of the microalbuminuria in these groups.
      Excluding the patients in the renal failure stage of the diabetic nephropathy or
      with other chronic diseases, our results confirm the data in the literature
      referring to the important role of the elevated diastolic blood pressure and
      elevated levels of the total plasma cholesterol in the rapid progression of the
      renal injury, especially after more than 8 years of IDDM evolution. We also
      found, between the long-term diabetics (over 15 years of evolution) a large
      proportion which appears to be genetically protected against the diabetic
      nephropathy. This point confirms some data from the literature (the Steno
      hypothesis). The HbA1C levels appears to lower with the duration of the diabetes
      and they are not correlated with the degree of the renal injury. These findings
      appear to be in contradiction with the data from the literature.

PMID- 8148777
TI  - Impaired glucose tolerance in the third trimester of pregnancy: associated
      factors to its persistence postpartum.
AB  - Glucose tolerance (75 g OGTT, according WHO) during the third trimester of
      pregnancy, in 302 women, has formerly been evaluated. Of these, 37 women were
      reinvestigated, with the same methodology, in absence of pregnancy and lactation,
      2 years postpartum. According to oral glucose tolerance three groups were
      differentiated: group A (n = 14) with normal glucose tolerance (NGT) both in
      pregnancy and postpartum. Group B1 (n = 12) with impaired glucose tolerance (IGT)
      in pregnancy but NGT postpartum. Group B2 (n = 11) with IGT both in pregnancy and
      postpartum. B2 group had increased values (mean + SD) for age (37.0 +/- 6.6
      years) versus B1 (30.2 +/- 5.5; p < 0.02) and A (29.5 +/- 5.9); p < 0.02) groups
      and BMI (32.5 +/- 4.2) versus 26.4 +/- 5.2; p < 0.01 and 23.3 +/- 4.4; p < 0.001
      respectively). The ratio between basal insulinogenic indexes (microU IRI/mg BG)
      during pregnancy and 2 years postpartum has been significantly reduced in B1 (1.4
      +/- 0.8) and B2 (1.5 +/- 0.6) as compared to A (2.5 +/- 1.1; p < 0.01) group
      suggesting, by comparison, the persistence of an increased level of insulin
      resistance postpartum in B1 and B2 groups. Insulinogenic index, after oral
      glucose was lower in B2 (34.4 +/- +/- 7.8) versus B1 (53.5 +/- 20.9; p < 0.01)
      group. These results suggest that, on an increased insulin resistance background,
      the decrease in glucose induced insulin response and increase in age and BMI are
      associated to deterioration of glucose tolerance early in the natural history of
      NIDDM.

PMID- 8148778
TI  - Low insulin secretion in decompensated liver cirrhosis with diabetes mellitus.
AB  - The present study aimed to investigate the pathogenesis of altered glucose
      tolerance frequently observed in liver cirrhosis by means of oral glucose
      tolerance test (OGTT) and i.v. glucagon followed by determining the
      immunoreactive insulinemia and insulinogenic index (Seltzer). In these conditions
      of beta islet cells upper limit stimulation a low insulin secretion was found in
      decompensated liver cirrhosis with alteration of the glucose tolerance (DM or
      IGT) and a tendency toward hepatic resistance to i.v. glucagon.

PMID- 8148779
TI  - Electron spin resonance study of the erythrocyte membrane fluidity changes in
      diabetes.
AB  - The membrane fluidity of intact erythrocytes from diabetic patients and sex
      matched controls has been examined between 20 and 40 degrees C by electron spin
      resonance spectroscopy using the 5-doxyl palmitic acid spin label. In contrast to
      the normal erythrocytes, in both types of diabetes a significant non-linearity
      was found around 30 degrees C in the fluidity-temperature plots of the lipid
      bilayer. This was assigned to a phase transition normally absent in the 20-40
      degrees C range. The magnitude of the bilayer fluidity showed a little decrease
      in insulin-dependent diabetes and an increasing trend vanishing around 37 degrees
      C in non-insulin-dependent diabetes. In addition, we observed two protein
      immobilized lipid subpopulations, showing slightly higher apparent concentrations
      and modified fluidity in diabetes. Membrane composition alterations, mainly in
      the fatty acid concentrations, may explain the fluidity changes. Our results,
      although preliminary in a clinical sense because the number of investigated
      patients was too small, evidenced specific and complex changes of the erythrocyte
      membrane fluidity in diabetes and demonstrated the high potential of the spin
      label approach for the diabetic medicine.

PMID- 8148780
TI  - Pancreatic B-cell culture after intravitam B-cell selection with nitric
      pilocarpine and modified B-technique use.
AB  - Our purpose was intravitam selection of endocrine pancreatic tissue. We decided
      to use 3% nitric pilocarpine as oral treatment for normal Wistar rats. This
      experiment was made on 12 male normal Wistar rats, 8 of them receiving 0.025 ml
      3% nitric pilocarpine in a single daily dose, for 7 days. In the next 3-4 days,
      all of these have demonstrated clinical picture of exocrine pancreatic failure
      leading finally to death. Animals have received ad libitum food-intake. During
      this period, the study group has demonstrated glycemia values between 65...75
      mg/dl vs. 68...85 mg/dl for normal group. The histological picture of study
      group's pancreatic pieces demonstrated intensive necrobiotic changes for exocrine
      components, but normal features for the exocrine ones. Furthermore we have
      obtained primary monolayer cultures of this dominant B-cell tissue, using a
      modified B-technique. Our results demonstrated the greatest percentage of B-cells
      on the cultures, in comparison with the non-using pilocarpine method (other
      studies). The presence of mega-beta-islet cells in primary cultures, as well as
      the lack of fibroblast population, demonstrated the efficiency of this method.

PMID- 8148781
TI  - Predictive value of glucose and proteic sulphur levels in the hair for an early
      detection of the preclinical stage of IDDM.
AB  - Assays of glucose and proteic sulphur levels in the hair of patients with
      recently detected IDDM provided information on the preclinical stage of insulin
      secretion disorders, which was estimated at 6 +/- 2 months. Such investigations
      in subjects at high risk of developing an IDDM might reveal the period preceding
      the disease onset, thus enabling to start an early therapy.

PMID- 8148782
TI  - Fear of hypoglycemia in type 1 (insulin-dependent) diabetic patients.
AB  - A clinical-psychological study was carried out in 224 insulin-dependent diabetic
      patients, distributed into two groups according to the frequency of hypoglycemic
      episodes. Group. A included 124 patients, 65 men and 59 women (mean age 35 +/- 18
      years), who reported frequent episodes of hypoglycemia (HG). In the 100 patients
      of group B (46 men and 54 women with a mean age of 37 +/- 10 years), the HG
      episodes were only occasional. The degree and type of anxiety were evaluated
      using: (1) a semistructured interview to determine the HG frequency and
      intensity; (2) the anxiety scale for HG, with two sections: a) 15 items about the
      behaviour to prevent HG occurrence and b) 10 items for the anxiety level; (3) the
      questionnaire of anxiety with 40 items. Highly significant differences between
      groups were found for the degree of anxiety about HG, particularly for the
      frequency of high anxiety scores (with ideative ruminations or generalized
      anxiety, accompanied or not by agoraphobia) (73.86% in group A versus 34.09% in
      group B; p < 0.001). Relatively significant differences were recorded with
      respect to the compliance to treatment (preventive behaviour for HG) as well as
      for the anxiety index (47.95% in group A versus 33.45% in group B), with a
      prevalence of the covered anxiety in group A and of the overt anxiety scores,
      indicating a dissimilation tendency of the adaptative role of anxiety as a signal
      of communication.

PMID- 8148783
TI  - Educational treatment manner of first choice for noninsulin dependent diabetes
      mellitus patients.

PMID- 8148784
TI  - Isolation of Borrelia burgdorferi in British Columbia.

PMID- 8148785
TI  - Lyme disease: seroprevalence and vector survey in southern Alberta.

PMID- 8148786
TI  - Three cluster outbreaks of tuberculosis in British Columbia.

PMID- 8148787
TI  - Control of tuberculosis transmission in health care settings. A joint statement
      of the WHO tuberculosis programme and the International Union Against
      Tuberculosis and Lung Disease (IUATLD).

PMID- 8148788
TI  - Effects of root planing on the distribution of microorganisms adult periodontitis
      sites.
AB  - The aims of this study were to identify the microbial species present in
      subgingival plaque in patients with adult periodontitis, and to investigate the
      effects of root planing upon the microbial flora for 12 months following root
      planing. Microorganisms from samples of subgingival plaque obtained from adult
      periodontitis sites in 15 patients were cultured, both aerobically and
      anaerobically, on a variety of media and identified. Prevotella intermedia and
      Porphyromonas asaccharolytica were the most frequently identified species before
      treatment. Bacteroides ureolyticus, the Prevotella veroralis/buccalis complex and
      other microorganisms including Capnocytophaga ochracea, species of streptococci,
      staphylococci and diphtheroids were also frequently isolated. Root planing
      improved periodontal health, and was accompanied by reductions in the frequencies
      with which P. intermedia, P. asaccharolytica, the P. veroralis/buccalis complex
      and C. ochracea were isolated. Regular scaling and oral hygiene reviews
      maintained the clinical improvements and balance in favour of beneficial
      microbial species during the study.

PMID- 8148789
TI  - Effect of microwave polymerisation on indentation creep, recovery and hardness of
      acrylic denture base materials.
AB  - With the advent of newer methods of activation of the polymerisation of denture
      base resins, there is a need to compare their physical properties using various
      modes of activation. Indentation creep, recovery and hardness of denture base
      resins polymerised either by microwave irradiation or heat were compared. A
      microwave curing cycle of 3 minutes at 500W was used. The Wallace microhardness
      tester and an indentation creep test were employed in order to evaluate the
      denture base resins. Under the experimental conditions of the study the results
      indicated that indentation creep, recovery and cyclic loading-deloading were
      similar in the resins polymerised by the two methods. Hardness was either similar
      or a softer produce was produced by microwave irradiation for two of the resins
      used. Hardness seems to be more sensitive to residual monomer levels, and for
      this reason a suitable microwave curing cycle should be employed to optimise all
      the physical properties.

PMID- 8148790
TI  - The tooth-denture base bond: stress analysis using the finite element method.
AB  - Although acrylic resin teeth are the most popular artificial teeth used for
      denture construction, a high number fracture away at the tooth-denture base
      interface. Various causes have been documented for this failure; however, it is
      logical that eventual fracture occurs due to localised tensile stresses at this
      interface. Examination of these stresses using the finite element method showed
      that on load application to the upper incisors, the maximum tensile stresses were
      concentrated within the body of the tooth and not at the tooth-denture base
      interface. Stresses encountered at the interface were relatively low and
      introduction of a crack made no significant difference to their magnitude.

PMID- 8148791
TI  - Assessment of masticatory efficiency: new methods appropriate for clinical
      research in dental practice.
AB  - A new chewing test has been assessed in which the test food was contained in a
      chewable rubber bag. Six subjects chewed ten single 'unbagged' almonds and ten
      single 'bagged' almonds. The bagged experiments gave generally similar results to
      unbagged ones in terms of the particle size distribution; they also proved more
      acceptable to the subjects and eliminated the serious, undefinable loss of chewed
      particles that occurs intraorally in conventional (unbagged) tests. In this study
      an optical scanning method was used which provided a simple, fast measurement of
      individual particles.

PMID- 8148792
TI  - Accuracy of fit of cobalt-chromium removable partial denture frameworks on master
      casts.
AB  - Fifty-six cobalt-chromium removable partial denture frameworks made to the same
      design were found to fit their master casts poorly. Spaces were significantly
      greater between palatal aspects of abutment teeth and palatal reciprocal arms,
      and between buccal aspects of occlusal rests and rest seats. Excessive
      contraction towards the centre of the palate was found. Expansion of the
      refractory investment may not have compensated adequately for solidification and
      cooling contraction of the cobalt-chromium alloy. Although dimensional changes in
      investment and casting are by volume, no evidence of anisotropic expansion of
      castings in a vertical direction was found.

PMID- 8148793
TI  - Masticatory efficiency of patients treated with implant retained fixed bridges in
      the upper jaw over a 2-year period.
AB  - The aim of this study was to investigate the effect of the rehabilitation of the
      upper jaw with a fixed bridge supported by Branemark implants upon patient's
      masticatory efficiency. Five patients wearing complete dentures in the upper jaw
      were selected for the study. Chewing tests using Optosil tablets were performed
      before fixture installation, immediately after bridge connection and 2 years
      after bridge delivery. The results indicated that treatment with fixed bridges
      retained by osseointegrated implants did not give immediate improvements in
      masticatory efficiency. Only after the subjects had enough time to adapt to the
      reconstruction was an improvement in the masticatory efficiency index observed.

PMID- 8148794
TI  - Proton magnetic resonance spectroscopy of cerebrospinal fluid as an aid in
      neurological diagnosis.
AB  - The proton magnetic resonance (1H-NMR) spectra were obtained from 38
      cerebrospinal fluid (CSF) samples from 34 patients with various central nervous
      system (CNS) diseases and the H2O signals were reduced by the presaturation
      method. A doublet signal for CH3 protons of lactate, as well as a singlet one for
      alpha-CH proton of glucose, were clearly detected in all the spectra obtained.
      The relative lactate concentration values were calculated on the basis of the
      glucose concentrations which had been measured by a routine laboratory method in
      the hospital and the ratios of the peak heights (lactate CH3/glucose alpha-CH).
      In the CSF samples examined, the relative lactate values semi-quantitatively
      determined in this way were clearly elevated in cerebral infarction and bacterial
      meningitis, but not in other disorders including viral meningitis. On the other
      hand, one CSF component whose enhancement was found only in a sample from a
      hepatic encephalitis patient was identified as glutamine from the double quantum
      filtered-shift correlation spectrum. These results suggest that 1H-NMR
      spectroscopy of CSF can become a powerful aid in biochemical diagnosis of CNS
      diseases.

PMID- 8148795
TI  - Differential aging pattern of cerebral accumulation of radiolabeled glucose and
      amino acid in the senescence accelerated mouse (SAM), a new model for the study
      of memory impairment.
AB  - Using an accelerated senescence-prone model mouse strain, SAMP8, with
      spontaneously occurring age-related deficits in learning and memory, cerebral
      glucose and amino acid accumulation were investigated to study the metabolic
      abnormalities in relation to age. The findings were compared with those in an
      accelerated senescence-resistant mouse strain, SAMR1, without deterioration of
      ability in learning and memory. [14C]-2-Deoxyglucose accumulation in the SAMP8
      brain was normal at 1 month of age but decreased from 2-3 months of age onwards.
      In contrast, tyrosine accumulation was unchanged from 1 to 5 months of age. The
      impairment of memory in the SAMP8 at 2-3 months of age corresponded with the
      decrease in [14C]-2-deoxyglucose accumulation, but was not related to Tyr. This
      animal model may help provide new information on the metabolic changes in aging.

PMID- 8148796
TI  - Pharmacokinetics of RK-28 (a new radiosensitizer) and pharmaceutical design of a
      suppository form using rats.
AB  - The pharmacokinetics of RK-28, a new hypoxic cell radiosensitizer, was studied in
      rats following its intravenous, intraportal, oral, and rectal administration. The
      pharmaceutical design of an RK-28 suppository form was also examined. After
      intravenous injection, RK-28 was rapidly removed from the plasma (biological half
      life of 17 min) and its area under the curve (AUC) was proportional to the amount
      of RK-28 administered. The absolute bioavailability of RK-28 was 59.7% for
      intraportal administration and 36.9% for oral administration. Following oral
      administration of RK-28, it seems likely that specific acid-catalyzed
      decomposition of RK-28 takes place in the stomach and then the absorbed RK-28
      undergoes first-pass metabolism in the liver. When "solidified RK-28
      suppository," made by solidifying molten RK-28, was inserted into the rectum,
      hepatic first-pass metabolism could be avoided substantially. The resulting
      absolute bioavailability of RK-28 increased to 75%. Furthermore, "RK-28 emulsion
      suppository," prepared by emulsifying RK-28 with 1-hexadecanol and hydrogenated
      castor oil (HCO 60) at 80 degrees C, showed a plasma concentration-time curve
      very suitable for radiation therapy; the maximum plasma concentration was
      attained 30 min after rectal administration and then decreased within a short
      period. Administration of "RK-28 emulsion suppository," resulted in an absolute
      bioavailability of 76%.

PMID- 8148798
TI  - Gastrointestinal physiology-regulated dogs: utilization of a bioavailability
      study of a new thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]-diazepine, an antagonist
      of platelet-activating factor, and its preparations.
AB  - The gastrointestinal (GI) physiology of beagle dogs was effectively regulated
      with a combined treatment using intramuscular pentagastrin (10 micrograms/kg x 2)
      and intravenous atropine sulfate (0.02 mg/kg x 1). The superiority of the GI
      physiology regulated-dogs over the intact dogs was confirmed by comparative
      bioavailability studies using two classes of preparations of poorly water-soluble
      4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H- thieno[3,2
      f][1,2,4]triazolo[4,3-a][1,4]diazepine (Y-24180). Both the fine granules and the
      tablets of Y-24180 exhibited similar absorption profiles in the intact dogs,
      whereas the latter preparations revealed a delayed plasma curve of the drug in
      the regulated-dogs. The absorption profiles of the two classes of Y-24180
      preparations in the regulated-dogs simulated those in healthy volunteers. The
      combined-treatment of beagle dogs with pentagastrin and atropine sulfate was
      suggested to supply a useful animal model for predicting the absorption
      characteristics of poorly water-soluble drugs and their preparations in humans.

PMID- 8148797
TI  - Effect of food on propranolol oral clearance and a possible mechanism of this
      food effect.
AB  - To better define the mechanism of the increased plasma concentration of
      propranolol (PL) after meals, the effect of the dietary constitution of a meal on
      the kinetics of PL and beta-naphthoxylactic acid (NLA), a main metabolite, after
      administration of the drug, was investigated in rats. Additionally, the hepatic
      uptake of PL and cytochrome P-450 (P-450) content and uridine 5'
      diphosphoglucuronyltransferase (UDPGT) activity in liver were measured after
      glucose intake. As a result, protein (skim milk) intake slightly, but not
      significantly, increased the area under the plasma concentration-time curve (AUC)
      and bioavailability of PL, with a slight increase (16%) in hepatic blood flow,
      and enhanced PL metabolism to NLA. Soybean oil and fatty acid intake
      significantly decreased the bioavailability of PL, while glucose intake
      dramatically decreased the hepatic uptake of PL and P-450 content at high glucose
      levels, resulting in a decrease in the plasma PL concentration at the initial
      time period and in the inhibition of a metabolic conversion to NLA. Thus, a
      possible mechanism involved in the effect of food on PL bioavailability could
      have been due largely to the decreased microsomal P-450 content and hepatic
      uptake of PL after glucose intake, but only partly to the increased hepatic blood
      flow after protein intake.

PMID- 8148799
TI  - Long circulating emulsion carrier systems for highly lipophilic drugs.
AB  - With the aim of developing of emulsion carrier systems for lipophilic drugs with
      the potential for prolonged circulation in the blood or hepatic targeting, the in
      vivo disposition of four model compounds, i.e., [3H]prostaglandin E1,
      [3H]retinoic acid, [14C]cholesterol, and [14C]cholesteryl oleate with calculated
      log PC(oct) values of 2.15, 6.61, 9.46, and 18.3, respectively, injected with
      various emulsion formulations, were studied in mice. Small sized emulsions of
      about 100 nm in diameters, with compositions of egg phosphatidylcholine (PC):
      soybean oil = 1:1 (small PC emulsion) and PC: egg sphingomyelin (SM): soybean oil
      = 0.7:0.3:1 (small SM emulsion), and a conventional emulsion with a diameter of
      about 250 nm and a composition of PC: soybean oil = 1:1 (large PC emulsion) were
      compared. Highly lipophilic [14C]cholesteryl oleate, a marker of emulsion
      particles, indicated diverse in vivo behaviors; i.e., the small SM emulsion
      produced prolonged circulation in the blood, and the small PC emulsion followed
      this, while the large PC emulsion was rapidly uptake by the liver. Thus, a
      reduction in size and coating with SM on the surface of oil droplets resulted in
      avoidance of the reticuloendothelial system (RES). Disposition profiles of other
      test compounds differed, depending on their lipophilicities: [14C]cholesterol
      showed disposition patterns in all formulations similar to those of
      [14C]cholesteryl oleate, but moderately lipophilic [3H]prostaglandin E1 and
      [3H]retinoic acid showed common disposition profiles, regardless of emulsion
      types, suggesting their rapid release from the emulsion carriers. These results
      suggest that small SM emulsion and large PC emulsion can act respectively as long
      circulating and liver targeting carriers for highly lipophilic drugs with log
      PC(oct) larger than 9.

PMID- 8148800
TI  - Evaluation of the thrombolytic effect of tissue-type plasminogen activator with
      ultrasonic irradiation: in vitro experiment involving assay of the fibrin
      degradation products from the clot.
AB  - Previous studies show that the combined method using thrombolytic drugs and
      ultrasonic irradiation enhances the effect of thrombolysis in in vitro and in
      vivo experiments. However, the mechanism of the clot lysis was unclear. In
      previous studies the evaluation of the clot lysis effect was determined by the
      rate of decrease in clot weight or the decrease in radioisotope-labeled
      fibrinogen in the clot. However, it was unclear whether or not the fibrinogen in
      the clot was degraded. We measured quantitatively the fibrin degradation product,
      D-dimer (FDP-DD), produced from clots subjected to recombinant tissue-type
      plasminogen activator (rt-PA, 2.0 micrograms/ml), with and without ultrasonic
      irradiation. Two levels of continuous ultrasound were used, 300 kHz (100 V, 0.07
      W/cm2) and 1 MHz (20 V, 0.4 W/cm2). The quantity of FDP-DD produced was 1.74
      times at 300 kHz and 1.80 times at 1 MHz, greater than that measured in rt-PA
      solution without ultrasonic irradiation; clot lysis was not observed in normal
      saline with ultrasonic irradiation. Our experiment clarifies that the mechanism
      of clot lysis when subjected to a combination of drug and ultrasound leads to
      degradation of fibrin, allowing a quantitative measurement of the enhancement of
      clot lysis. A high correlation was observed between the FDP-DD produced from the
      clots and the rate of decrease in clot weight.

PMID- 8148801
TI  - Relationship between the tissue distribution and antitumor activity of highly
      branched (1-->3)-beta-D-glucan, SSG.
AB  - Distribution of 3H-labeled (1-->3)-beta-D-glucan([3H]SSG) obtained from the
      culture filtrate of Sclerotinia sclerotiorum IFO 9395, in various tissues in
      tumor-bearing mice was examined. [3H]SSG administered intra-peritoneally was
      mainly detected in liver, spleen, kidney and tumor masses. In contrast to i.p.
      administration, intra-lesionally administered [3H]SSG was not released from the
      tumor. Similarly, in a double grafted tumor system, [3H]SSG was located in the
      administered tumor and not distributed in the distant site tumor, in spite of the
      fact that significant antitumor effect was shown in both tumor sites in this
      system. Winn assay confirmed the activation of the systemic antitumor immunity.
      These results suggested that the distribution of glucans would be one important
      factor in determining their antitumor effects. However, this would not always be
      necessary if systemic immunity could be induced.

PMID- 8148802
TI  - Evaluation of antiseptics by the modified phenol coefficient method: sensitivity
      of methicillin-resistant Staphylococcus aureus.
AB  - The relationship between an effective concentration and the duration of exposure
      to antiseptics was evaluated in strains of Staphylococcus aureus with a known
      genetic background, which include methicillin-resistant strains, using a modified
      version of the phenol coefficient method as part of an effort to investigate the
      antiseptic resistance of S. aureus. Chlorhexidine digluconate killed an
      antiseptic-sensitive strain within 1.5 min at 22 degrees C at a standard
      concentration (0.1%), whereas resistant strains still survived after 1.5 min.
      Povidone-iodine killed the sensitive strain within 1.5 min at a concentration of
      0.1%, whereas it took this agent 3.0 and 4.5 min to kill low- and high-level
      resistant strains, respectively, at a concentration of 0.8%. These results
      indicate that the modified phenol coefficient method used is suitable for the
      evaluation of the sensitivity of microorganisms to antiseptics. An antiseptic
      resistant chain that was associated with the ebr gene exhibited cross-resistance
      to povidone-iodine.

PMID- 8148803
TI  - Colorimetric determination of urinary xanthurenic acid using an oxidative
      coupling reaction with N,N-diethyl-p-phenylenediamine.
AB  - A simple enzymatic method for the spectrophotometric determination of xanthurenic
      acid (XA) in urine is described. The method is based on the formation of a
      pigment derived from an oxidative coupling reaction with XA and N,N-diethyl-p
      phenylenediamine (DE-PPD) in the presence of hydrogen peroxide and horseradish
      peroxidase. The color of the reaction mixture was developed with a peak
      absorbance at 750 nm. The recoveries against XA added to urine ranged from 91.0
      to 96.5%. With this method, XA can be determined within 5 min, without a time
      consuming sample preparation. The detection range of this method was between 5
      and 150 microM, with a coefficient of variation of 2.7% or less. The correlation
      between this and the fluorometric method was  good.

PMID- 8148804
TI  - Urinary levels of gamma-carboxyglutamic acid and its clinical significance.
AB  - Urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in healthy
      subjects of all ages. The urinary gamma-Gla levels were highest in infants (0-1
      years), then fell in an age-dependent manner, again in subjects reaching a
      minimum value in adults, then gradually increased over 60 years of age. Urinary
      gamma-Gla levels therefore change markedly with aging. The relationships between
      the urinary gamma-Gla excretion and plasma levels of prothrombin and protein C in
      patients with various hepatic diseases or diabetes mellitus were examined and
      compared with those in healthy adults. Both plasma prothrombin and protein C
      levels were decreased in all patients with liver disease compared with healthy
      adults. In patients with hepatitis and liver cirrhosis, the decrease did not,
      however, affect the gamma-Gla excretion. In addition, in patients with hepatoma
      or carcinoma with liver metastases, the urinary gamma-Gla levels were increased.
      In patients with diabetes mellitus, the urinary gamma-Gla levels and plasma
      levels of prothrombin and protein C tended to increase, but this was not
      significant. The present results indicate that simultaneous measurement of the
      levels of urinary gamma-Gla and plasma prothrombin and protein C is a useful tool
      for the diagnosis of liver diseases and diabetes mellitus.

PMID- 8148805
TI  - Antioxidative effects of black tea theaflavins and thearubigin on lipid
      peroxidation of rat liver homogenates induced by tert-butyl hydroperoxide.
AB  - The antioxidative activity of theaflavins (TFs) and thearubigin (TR) purified
      from the infusion of black tea leaves was examined using the tert-butyl
      hydroperoxide-induced lipid peroxidation of rat liver homogenates. The
      concentrations which produced 50% inhibition of lipid peroxidation (IC50) by
      theaflavin (TF), theaflavin monogallate-A (TFM-A), and TR were 4.88 x 10(-4),
      4.09 x 10(-4), and 4.95 x 10(-4%) (w/v), respectively. The anti-oxidative
      activity of these compounds was higher than that of glutathione, L(+)-ascorbic
      acid, dl-alpha-tocopherol, butylated hydroxytoluene, butyl hydroxyanisole, etc.,
      but was lower than the activity of (-)-epicatechin gallate, (-)-epigallocatechin,
      and (-)-epigallocatechin gallate. As to the IC50 in molarity, the antioxidative
      activity of TFM-A was the second highest among all the samples used in this
      study. The antioxidative activity of lyophilized tea infusions was compared. The
      activity of black tea was about as potent as that of green tea. These results
      suggest that black tea infusion containing TFs and TR could inhibit lipid
      peroxidation in biological conditions in the same way as green tea infusion
      containing epicatechins.

PMID- 8148806
TI  - Production of choleretic substances in the capitulum, leaf and stem of Artemisia
      capillaris during the plant growth cycle.
AB  - Five Artemisia capillaris plants were selected at random from among a bed of
      twenty plants cultivated in a field for one year. Several branches were collected
      from each plant once a month, except in August and October, when two collections
      were made during budding and flowering. Each organ (leaf, stem, and capitulum)
      was separated from the branch and dried, and later analyzed for capillarisin and
      6,7-dimethylesculetin content by high-performance liquid chromatography (HPLC).
      The capillarisin and 6,7-dimethylesculetin content reached maximum levels in the
      leaf just before the appearance of flower buds at end of July. About one month
      later, at the end of August during budding and flowering, capillarisin content in
      the capitulum reached a peak and then decreased. On the other hand, 6,7
      dimethylescuretin content reached a maximum at the beginning of September, two
      weeks after the capillarisin maximum. The results suggest that the most
      appropriate time to harvest A. capillaris for use as a crude drug is between the
      flower bud stage and early flower stage, from late August to early September.

PMID- 8148807
TI  - Comparative study of permeability into rat cerebrospinal fluid of the quinolones:
      dependency on their lipophilicities.
AB  - Pharmacokinetic behavior involved in the entry of four quinolone antibacterial
      agents, norfloxacin (NFLX), ciprofloxacin (CPFX), ofloxacin (OFLX) and nalidixic
      acid (NA), into cerebrospinal fluid (CSF) was comparatively investigated in rats.
      Periodically, after the bolus i.v. dose of each quinolone (10 mg/kg), aliquots of
      CSF were collected by cisternal puncture and blood samples were then withdrawn
      from the jugular vein. CSF and serum (total and unbound) levels of the drugs were
      determined by HPLC method. Transport parameters for three new quinolones (NFLX,
      CPFX, OFLX) into CSF were obtained by physiological model analysis. Serum levels
      of OFLX and NFLX declined bi-exponentially with time, whereas the serum levels of
      NA and CPFX declined in mono-exponential and tri-exponential fashion,
      respectively. Fractions of each quinolone unbound to serum protein (approximately
      0.7 for NFLX, CPFX, and OFLX, 0.12 for NA) were almost the same at any point in
      time. The CSF levels of these quinolones rose quite rapidly after drug
      administration, and then declined, along with their serum levels. Both the CSF
      level and the ratio of CSF concentration to serum unbound concentration were the
      highest for NA, followed by OFLX, CPFX and NFLX. These values of the four
      quinolones were almost proportional to the apparent partition coefficient (Papp)
      between n-octanol and phosphate buffer (pH 7.0) values of each reported in a
      previous paper [Tsuji et al., Antimicrob. Agents Chemother., 32, 190 (1988)]. In
      the three new quinolones, OFLX had a larger value of apparent diffusional
      clearance between blood and CSF (PAc) than CPFX and NFLX.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8148808
TI  - Gas chromatographic-mass spectrometric determination of 13C-glucose level for
      evaluating the effect of alpha-glucosidase inhibitor acarbose on the digestion of
      [U-13C] starch in rat.
AB  - The effect of acarbose on the digestion of starch was examined by a stable
      isotope tracer technique. [U-13C]-Starch was administered orally to rats with or
      without acarbose. After the addition of [2H3]-D-glucose as the internal standard,
      the plasma samples were treated successively for defatting, deproteinizing and
      desalting. Glucose was converted to sorbitol by reduction with sodium
      borohydride. The cyclic butylboronate of sorbitol was injected into a gas
      chromatograph-mass spectrometer, and the concentration of labeled glucose was
      measured by selected monitoring of the quasi-molecular ion. The plasma
      concentration of labeled glucose was decreased significantly by the addition of
      acarbose. The effect of acarbose on the digestion of starch was clearly confirmed
      using [U-13C]starch.

PMID- 8148809
TI  - Drug binding properties of glycosylated human serum albumin as measured by
      fluorescence and circular dichroism.
AB  - Binding properties of Sudlow's site-specific drugs to glycosylated human serum
      albumin (G-HSA) were investigated using fluorescence and circular dichroism (CD).
      Dansylamide, phenylbutazone and warfarin were used as site I-specific drugs, and
      dansylproline, ibuprofen and flufenamic acid were used as site II-specific ones.
      Similar changes in the fluorescence intensity of dansylamide occurred in the
      presence of both G-HSA and intact human serum albumin (HSA), while the
      fluorescence enhancement of dansylproline caused by G-HSA was extremely weakened
      in comparison with that by HSA. These results suggest that the glycosylation of
      HSA inhibits the binding of the site II-specific drug, dansylproline, to HSA,
      while it does not influence the binding of the site I specific drug, dansylamide.
      The induced ellipticities of the complexes of ibuprofen, flufenamic acid and
      phenyl butazone with G-HSA were diminished in comparison with those with HSA.
      With the complexes of warfarin, the induced ellipticity was enhanced. These CD
      results suggest that the glycosylation of HSA induces microenvironmental changes
      in the binding sites for the above site-specific drugs which influence the drug
      binding ability of HSA.

PMID- 8148810
TI  - Phytogrowth-inhibitory activities of 2-thiophenecarboxylic acid and its related
      compounds.
AB  - 2-Thiophenecarboxylic acid (I) exhibited growth-inhibitory activity in five kinds
      of plants. In particular, I strongly inhibited the growth of the roots of Lactuca
      sativa L. var. longifolia LAM and Echinochloa utilis OHWI et YABUNO, even at the
      low concentration of 5.0 x 10(-3) M. Furthermore, all of the I-related compounds
      (II-V and VII-X) except for VI, showed more or less obvious inhibitory activity
      on the seeds of Sesamum indicum L. Compounds VII-X, in which the carboxyl group
      of I was replaced by acetic acid, propionic acid, butyric acid and acrylic acid,
      and exhibited more potent phytogrowth-inhibitory activity than I. Among these
      compounds, 2-thiophenebutyric acid (IX) showed the strongest activity.
      Esterification of the carboxyl group in I increased the inhibitory activity
      relative to that of I, while amidation and reduction of this group markedly
      decreased its inhibitory activity. The radicles of the plants treated with each
      of the compounds except for VI showed negative geotropism, even though
      germination occurred.

PMID- 8148812
TI  - Calcein release from temperature-sensitive liposome with or without stirring.
AB  - Characteristics of the calcein release from temperature-sensitive liposomes with
      or without stirring were studied. Calcein release from
      DPPC(dipalmitoylphosphatidylcholine) REV(reverse phase evaporation vesicle) with
      stirring occurred at a temperature lower by 8 degrees than that without stirring.
      DPPC-DSPC(distearoylphosphatidylcholine)-mixed REV showed the maximum release(%)
      for calcein, near 40 degrees C with stirring and 45 degrees C without stirring.

PMID- 8148811
TI  - Substrates and inhibitors of antiseptic resistance in Staphylococcus aureus.
AB  - The range of substrates of antiseptic resistance associated with the ebr gene is
      very wide and includes antiseptics, DNA-intercalating drugs and preservatives
      which have no quaternary ammonium group in methicillin-resistant Staphylococcus
      aureus. Antiseptic resistance was inhibited by calcium channel blockers and
      calmodulin inhibitors similarly to the resistance to multiple antitumor agents
      encoded by the mdr gene in human cells. These results show that the common
      properties of the mdr gene and the ebr gene may be shared by the mechanisms that
      are involved in the removal of toxic substances from the cell.

PMID- 8148813
TI  - Nerve growth factor content of rat brain increases following basal-forebrain
      lesions induced by ibotenic acid but not by electrolysis.
AB  - We attempted to measure the change in the nerve growth factor (NGF) content in
      the hippocampus and parietal cortex following basal-forebrain lesions induced by
      ibotenic acid and electrolysis. The NGF content of the parietal cortex and
      hippocampus increased transiently on days 3 to 7, and then returned to the
      control level on day 14 after the lesion of the basal forebrain induced by
      ibotenic acid. Ibotenic acid decreased both the choline acetyltransferase (ChAT)
      activity in the parietal cortex and the dopamine content in the striatum.
      Electrolytic lesions of the basal forebrain decreased the dopamine content in the
      striatum, but did not affect the NGF content and ChAT activity in any of the
      brain regions examined. These results suggest that the mechanism of NGF synthesis
      is related to cholinergic, but not to dopaminergic, neurons in the basal
      forebrain.

PMID- 8148814
TI  - A simple method for the assessment of macrophage scavenger receptor-ligand
      interaction: adherence of erythrocytes coated with oxidized low density
      lipoprotein and modified albumin to macrophages.
AB  - A simple method is described for the assessment of the binding of macrophage
      scavenger receptor and its ligands such as oxidized low density lipoprotein (ox
      LDL) and maleylated bovine serum albumin (m-BSA). In this method, the binding of
      ox-LDL or m-BSA to macrophages is observed as the adherence of erythrocytes
      precoated with ox-LDL or m-BSA under phase-contrast microscopy. Erythrocytes were
      coated with native LDL or ox-LDL simply by incubating mouse erythrocytes with
      LDL. The ox-LDL-coated erythrocytes attached to the monolayer of mouse peritoneal
      macrophages without phagocytosis at 37 degrees C, while native LDL-coated
      erythrocytes did not. The extent of the adherence of the ox-LDL-coated
      erythrocytes to the macrophages was conveniently expressed as the proportion of
      the macrophages binding the coated erythrocytes. An optimal concentration of ox
      LDL for erythrocyte coating giving maximum erythrocyte adherence to macrophages
      was 10 micrograms/ml as protein at an erythrocyte concentration of 2%. The
      binding of the ox-LDL-coated erythrocytes to the macrophages could be inhibited
      by ligands for scavenger receptor, and reflected the extent of LDL oxidation.
      Mouse erythrocytes were successfully coated with m-BSA using chromium(III) ion as
      adsorbent. The m-BSA-coated erythrocytes attached to the macrophages, while
      native BSA-coated erythrocytes did not. The adherence was inhibitable with
      ligands for scavenger receptor, and reflected the extent of maleylation. The
      method would be useful particularly for measurement of the ligand-binding
      activity of the receptor, and the receptor-binding activity of the ligands.

PMID- 8148815
TI  - Characterization of cytosolic phospholipase A2 in rat mastocytoma RBL-2H3.
AB  - We previously reported that cultured mast cells expressed three discrete
      phospholipases A2 (PLA2S), one of which showed a remarkable preference for
      phospholipids bearing an arachidonoyl residue at the sn-2 position [M. Murakami,
      et al., J. Biochem., 111, 175 (1992)]. In the present study, we have purified and
      characterized this enzyme using rat mastocytoma RBL-2H3 as an enzyme source. The
      elution profiles of the arachidonoyl-preferential PLA2 activity of rat
      mastocytoma RBL-2H3 cells on several column chromatographies were
      indistinguishable from those of 85-kDa cytosolic PLA2 (cPLA2) characterized so
      far. The molecular mass of the partially purified PLA2 was estimated to be about
      90 kDa by gel filtration and it hydrolyzed arachidonate-containing phospholipids
      preferentially in the presence of submicromolar Ca2+ concentrations. Furthermore,
      it was immunoprecipitated with an anti-rabbit cPLA2 antibody almost completely.
      From these observations, we have concluded that the arachidonoyl-preferential
      PLA2 in mast cells belongs to the "cPLA2" family.

PMID- 8148816
TI  - Radioimmunoassay of conjugated 1 beta-hydroxycholic acid in dried blood spots for
      diagnosis of congenital biliary atresia.
AB  - Radioimmunological measurement of conjugated 1 beta-hydroxycholic acid in dried
      blood spots obtained from newborns at 4-5 d after birth has been carried out to
      investigate a diagnostic utility for congenital biliary atresia. The method
      allowed the determination of this bile acid, with a detection limit of 50 pg in
      one disc (3 mm i.d.), and showed good reproducibility with inter- and intra-assay
      coefficients with variations of 3.5-7.7% and 6.3-8.8%. With the analysis, a
      relatively high concentration of this substance was observed in the patients, as
      compared to normal subjects, averaging 1.63 ng/disc in the former and 0.97
      ng/disc in the latter.

PMID- 8148817
TI  - Modification of delipidated apoprotein B of low density lipoprotein by lipid
      oxidation products in relation to macrophage scavenger receptor binding.
AB  - It is known that macrophages recognize and take up oxidized low density
      lipoprotein (LDL) and this macrophage recognition has been suggested to be due to
      modification of the lysine (Lys) residues of apoprotein B (apo B). In order to
      determine whether such modification is involved in recognition, delipidated apo B
      was modified with lipid peroxidation products and the macrophage recognition of
      the modified apo B was examined. When delipidated apo B was treated with linoleic
      acid 13-mono-hydroperoxide (LOOH) and trans-2-octenal (octenal), apo B became
      fluorescent and its Lys and histidine (His) residues were decreased. When
      delipidated apo B, partially methylated at the epsilon-amino groups of Lys
      residues, was treated with LOOH and octenal, fluorescence was not produced and
      the free Lys residues were not decreased. LOOH- and octenal-modified delipidated
      apo B were recognized by mouse peritoneal macrophages. The macrophage recognition
      of the modified apo B was prevented by maleyl bovine serum albumin, indicating
      that the scavenger receptor was involved in recognition. Neither methyl apo B nor
      methyl apo B, modified with LOOH or octenal, was recognized by macrophages.
      Neutralization of positively charged Lys residues of apo B by modification with
      LOOH and octenal may be requisite for recognition. Bovine serum albumin modified
      with LOOH and octenal prevented the recognition of the modified apo B, indicating
      that none of the intrinsic structure of apo B is required for recognition.

PMID- 8148818
TI  - Effect of a benzylidene derivative, novel antirheumatic agent, on the production
      of tissue inhibitor of metalloproteinases.
AB  - We investigated the effects of PAL (protocatechualdehyde), a metabolite of ACP
      (3,4-diacetoxy benzylidene diacetate) which is a candidate as a novel
      antirheumatic agent, on the production of a tissue inhibitor of
      metalloproteinases (TIMP) using a primary chondrocyte culture from bovine nasal
      septum cartilage. The addition of human recombinant interleukin-1 alpha (hrIL-1
      alpha) induced proteoglycan (PG) depletion from a chondrocyte matrix. PAL
      significantly reduced the induction of PG depletion. HrIL-1 alpha increased the
      casein-degrading activity, matrix metalloproteinase (MMP) activity, and the level
      of TIMP secretion in the culture media. PAL significantly reduced the casein
      degrading activity and further increased TIMP secretion under hrIL-1 alpha
      stimulation. Phorbol myristate acetate (PMA) also increased the level of TIMP
      secretion, and staurosporine, a specific inhibitor of protein kinase C (PKC),
      reduced the TIMP secretion to the control level under hrIL-1 alpha or PMA
      stimulation. Furthermore, PAL showed a significant increase following treatment
      with a low concentration of PMA which alone did not increase TIMP production.
      These findings suggest that the activation of the PKC pathway plays an important
      role in TIMP production and that PAL increases the level of TIMP production
      through an additive or synergistic effect with the activation of the PKC pathway.
      In conclusion, these findings demonstrate that the inhibition of the MMP activity
      and the increase of TIMP production by PAL contribute to the inhibition of PG
      depletion in a primary chondrocyte culture from bovine nasal septum cartilage.

PMID- 8148819
TI  - Effect of some peptidase inhibitors on exogenous and endogenous opioid actions in
      guinea-pig ileum.
AB  - Met-enkephalin concentration-dependently and transiently inhibited the ileal
      twitch contraction and this inhibition gradually recovered with time. Bacitracin,
      phosphoramidon, thiorphan and captopril did not influence the twitch inhibition
      of met-enkephalin, but bestatin increased the twitch inhibitory potency of met
      enkephalin and terminated it in a manner which almost paralleled that of
      untreated tissue. Transient inhibition of twitch contraction after tetanic
      stimulation (post-tetanic twitch inhibition) was obtained. Bestatin increased the
      potency of met-enkephalin and this was terminated within 2 min. Phosphoramidon
      tended to increase the potency and delayed the termination of post-tetanic twitch
      inhibition. Bacitracin, thiorphan and captopril did not influence either the
      potency or the termination of post-tetanic twitch inhibition. Morphine-induced
      twitch inhibition was not influenced by bacitracin, bestatin or phosphoramidon.
      These results suggest that bestatin-sensitive aminopeptidase and phosphoramidon
      sensitive enkephalinase take part in post-tetanic twitch inhibition, acting in a
      different mode of action, and have an important role in the termination of the
      pharmacological action of endogenous opioids (post-tetanic twitch inhibition) in
      MPLM. This different mode of response of bestatin and phosphoramidon upon post
      tetanic twitch inhibition may underlie that aminopeptidase is a more soluble
      enzyme and enkephalinase is membrane-bound in myenteric plexus-longitudinal
      muscle (MPLM).

PMID- 8148820
TI  - Synergistic enhancement of nitrite on lysophospholipid-mediated cytolysis.
AB  - Nitrogen oxide, which is produced by activated macrophages, has been demonstrated
      to possess anti-tumor activity. We report herein the synergistic effect of sodium
      nitrite (NO2-) and/or sodium nitroprusside (SNP) on lysophospholipid (LysoPL)
      mediated cytolysis. The incubation of 51Cr-labeled mouse melanoma (B16) cells
      with NO2- alone for 3 h at 37 degrees C did not induce cytolysis. On the other
      hand, NO2- significantly enhanced the cytolysis of B16 cells in the presence of
      lysophosphatidylcholine (LysoPC; 2.0 microM). A similar effect of NO2- on B16
      cytolysis was also observed in the presence of 1-O-alkyl-sn-glycero-3
      phosphocholine (LysoPAF). In addition, SNP (0.05-0.5 mM) synergistically enhanced
      B16-cytolysis in the presence of LysoPC. However, nitrate had no effect on the
      cytolysis of B16 cells treated with LysoPC. Furthermore, NO2- synergistically
      enhanced the hemolysis of sheep erythrocytes in the presence of LysoPC, but not
      in the presence of an anti-sheep erythrocyte antibody and complement. These
      findings suggest that NO2- directly affects membrane damage in the presence of
      LysoPL.

PMID- 8148821
TI  - Cytotoxicity of chlorinated hydrocarbons and lipid peroxidation in isolated rat
      hepatocytes.
AB  - The effects of 11 chlorinated hydrocarbons on toxicological parameters and lipid
      peroxidation were examined in cultured rat hepatocytes. The cytotoxicity was
      evaluated by measuring the lactate dehydrogenase (LDH) released and the protein
      amount in cells attached to culture dishes. Phosphatidylcholine hydroperoxide
      (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) levels were determined
      by HPLC with chemiluminescence detection (CL-HPLC). Severe cytotoxicity was
      observed under the presence of the carbon tetrachloride, 1,1,1-trichloroethane,
      tetrachloroethylene and 1,3-dichloropropene in a concentration of 10 mM. The
      cellular PCOOH and PEOOH levels were remarkably increased (more than 4 times) by
      adding these 4 chlorinated hydrocarbons. The other 7 chlorinated hydrocarbons
      examined did not cause any change on the cellular phospholipid hydroperoxide
      levels, and showed lower or no cytotoxicity at a concentration of 10 mM. The
      peroxidative degradation of membrane phospholipids may play an important role in
      causing the cytotoxicity of some chlorinated hydrocarbons.

PMID- 8148822
TI  - Examination of the extraction methods and re-evaluation of blue fluorescence
      generated in rat tissues in situ.
AB  - Extraction methods for measuring blue fluorescence generated in rat liver and
      brain in situ were examined. Great care should be taken when the traditional
      chloroform/methanol extraction method is employed because artificial blue
      fluorescence is readily produced by subsequent light irradiation, or by passage
      through a silicic acid column. In contrast, sodium dodecylsulfate (SDS)
      extraction were found to be suitable since no artificial blue fluorescence was
      produced by subsequent light irradiation. The levels of blue fluorescence in rat
      tissues were re-evaluated following SDS extraction. The levels of blue
      fluorescence in rat liver increased with age, whereas those in rat brain did not.
      Accumulation of blue fluorescence in the tissues was only slightly enhanced by
      vitamin E-deficiency. Blue fluorescence in the extracts did not seem to be
      derived from autofluorescent yellow lipofuscin in situ. The results were not
      always consistent with earlier observations obtained using the
      chloroform/methanol extraction.

PMID- 8148823
TI  - Development of glycoside-bound radiopharmaceuticals: novel radioiodination method
      for digoxin.
AB  - We combined 2-hydroxy-3-methylbenzoylhydrazide (HMBH) with glycosides as a novel
      method for the radioiodination of physiologically active glycosides. This method
      was tested using digoxin, which is one of the cardiac glycosides. A digoxin-HMBH
      conjugate was synthesized by periodate cleavage of the third sugar ring, and was
      readily radiolabeled with Na[125I] by the chloramine-T method. 125I labelled
      digoxin-HMBH conjugate retained Na+, K(+)-ATPase binding in vivo and in vitro,
      and also retained immunoreactivity to an anti-digoxin antibody. Thus, this 125I
      labelled digoxin-HMBH conjugate represents a potential radiopharmaceutical for
      Na+, K(+)-ATPase imaging, as well as for the radioimmunoassay of digoxin.

PMID- 8148824
TI  - Tea not tranquillisers.

PMID- 8148825
TI  - Why invest in home care?

PMID- 8148826
TI  - Rough and tumble guide to laundering.

PMID- 8148827
TI  - Promoting good practice.

PMID- 8148828
TI  - Do you really have to fill that job?

PMID- 8148829
TI  - Swimming in health.

PMID- 8148830
TI  - Gerontological gender gap.

PMID- 8148831
TI  - Straight from the pack.

PMID- 8148832
TI  - An old kind of caring.

PMID- 8148833
TI  - As I was saying ... the third age.

PMID- 8148834
TI  - Equilibrium and non-equilibrium partition of tritium between organics and tissue
      water of different biological systems.
AB  - The biological tritium fractionation factor, accompanying the equilibrium
      partition of tritium between the organic and the aqueous phases of the biosystem
      through isotope effects on the enzyme reactions of its metabolism, has been
      determined. The ratio (R) of the specific activities of organically bound tritium
      and tissue water tritium has been measured under special conditions to eliminate
      analytical as well as biological interfering effects that possibly alter the
      experimental R value. Two plant categories with distinct photosynthetic CO2
      fixation pathways, adapted to their different water use efficiency, namely barley
      (C3 plant) and maize (C4 plant), have been compared in order to estimate the
      natural variation of the biological tritium fractionation factors among different
      biosystems.

PMID- 8148835
TI  - The U.S. physician supply: generalism in retreat.

PMID- 8148836
TI  - Urban health care delivery systems in the 1980s.

PMID- 8148837
TI  - A success story--waiting to be retold: methadone treatment in New York City.

PMID- 8148838
TI  - Providing health services for the homeless: a stitch in time.

PMID- 8148839
TI  - Bringing comprehensive health education to the New York City Public Schools: a
      private-public success story.
AB  - The New York Academy of Medicine has pioneered a far-sighted effort which
      successfully introduced two model health education curricula into the New York
      City Public Schools at both the elementary and middle school levels. The
      curriculums for kindergarten through sixth grades, Growing Healthy, are currently
      being used in 525 of New York's 625 elementary schools, and the curriculum for
      seventh and eighth grades, Being Healthy, is in place in 60 of 200 junior high
      schools. These curricula offer a comprehensive approach to health education that
      promotes emotional well-being as well as physical health by improving health
      behaviors, attitudes, and academic performance of students through hands-on and
      interactive activities which develop decision-making skills and the ability to
      make healthful choices. The program has met with ongoing success and expanding
      influence, as the result of several important factors. First, the New York
      Academy of Medicine took a leadership role in supporting a venture outside its
      own walls and became an active advocate for comprehensive health education in the
      public schools. The Academy's standing as a prestigious yet independent medical
      association brought influence to the organizing efforts and contributed the
      credibility needed to get the program off the ground. Second, the Division of
      Student Support Services of the New York City Public Schools gave strong
      acceptance and cooperation leading to ongoing financial support and
      institutionalization of the program. Added to that is the enthusiasm of teachers,
      administrators, and other in-school personnel who have made the lessons of
      Growing Healthy and Being Healthy meaningful by reaching hundreds of thousands of
      students across New York City. Another important factor is the oversight and
      longevity which has been provided by the unusual gathering of doctors, educators,
      public health specialists, funders, and city administrators who created an
      effective private-public coalition 15 years ago and have remained committed to
      working together. Last through its ongoing efforts, the Academy's Office of
      School Health Programs has stayed at the forefront of developments in health
      education. By continuing to evaluate their activities and by constantly
      integrating new materials into the existing curricular framework, they have
      demonstrated that a comprehensive health education program can be both meaningful
      to children and responsive to community needs by reflecting current public health
      issues and concerns.

PMID- 8148840
TI  - The Know Your Body program: a review of evaluation studies.
AB  - Know Your Body is a comprehensive school health promotion program for
      kindergarten through six grades, initially developed in the 1970s by the American
      Health Foundation. The impact of the KYB program has been evaluated in three
      field trials, the results of which have been reviewed in this article. Across the
      three studies, at 3-year follow-up, consistent positive intervention effects were
      reported for systolic blood pressure, diastolic blood pressure, smoking, HDL
      cholesterol, and health knowledge. Results for total blood cholesterol, fitness
      score, heart-healthy snacks, fruit/vegetable intake, whole milk intake, and
      health attitudes were mixed. For body mass index, triceps skinfold, all remaining
      dietary variables, self-esteem/self-efficacy, and locus of control no significant
      effects were observed. Overall, significant treatment effects were reported for
      19 of the 40 variables assessed at 3-year follow-up, an effects ratio of 48%.
      Consistent positive results at 5-year follow-up were reported for smoking and
      health knowledge. Mixed results were obtained for total blood cholesterol,
      diastolic blood pressure, and percent kilocalories from saturated fat. Consistent
      null results were reported for HDL-cholesterol, systolic blood pressure, body
      mass index, triceps skinfold, fitness score, percentage kilocalories from fat,
      cholesterol intake, and fiber intake. Overall, significant treatment effects were
      reported for 7 of 36 variables at 5-year follow-up, an effects ratio of 19%.
      Although reported program effects were largely mixed, they seem consistent with
      other health education evaluations. Null results may have been related to
      insufficient teacher implementation as well as weaknesses in design and
      assessment. Additional research is needed to determine the effect of the program
      on a broader range of outcomes, to what degree increasing the "dose" produces
      larger and more enduring treatment effects, and the relative impact of the
      various components that comprise the program.

PMID- 8148841
TI  - Health needs of incarcerated youth.
AB  - From a health care point-of-view, the most needy adolescents in the United States
      are those who become incarcerated in the juvenile justice system. These
      youngsters have poor health care before incarceration is not much better. Their
      health problems range from the results of trauma to the consequences of sexual
      activity to severe psychological problems. Their health needs include: (1)
      prevention of health problems which contribute to behaviors for which youths are
      incarcerated; (2) comprehensive assessment and care; (3) continuity of care after
      discharge from the institutions; (4) comprehensive health education and health
      promotion; (5) professional, competent health care providers; (6) educated,
      sympathetic administrators and supervisory personnel; and (7) adequate financing
      of health services. Concerned health providers must become advocates for these
      adolescents and for their health care in correctional and political settings.

PMID- 8148842
TI  - Adolescents and access to health care.
AB  - The developmental characteristics and health behaviors of adolescents make the
      availability of certain services--including reproductive health services,
      diagnosis and treatment of sexually transmitted disease, mental health and
      substance abuse counseling and treatment--critically important. Furthermore, to
      serve adolescents appropriately, services must be available in a wide range of
      health care settings, including community-based adolescent health, family
      planning and public health clinics, school-based and school-linked health
      clinics, physicians' offices, HMOs, and hospitals. National, authoritative
      content standards (for example, the American Medical Association's Guidelines for
      Adolescent Preventive Services (GAPS), a multispecialty, interdisciplinary
      guideline for a package of clinical preventive services for adolescents may
      increase the possibility that insurers will cover adolescent preventive services,
      and that these services will become part of health professionals' curricula and
      thus part of routine practice. However, additional and specific guidelines
      mandating specific services that must be available to adolescents in clinical
      settings (whether in schools or in communities) are also needed. Although local
      government, parents, providers, and schools must assume responsibility for
      ensuring that health services are available and accessible to adolescents,
      federal and state financing mandates are also needed to assist communities and
      providers in achieving these goals. The limitations in what even comprehensive
      programs currently are able to provide, and the dismally low rates of preventive
      service delivery to adolescents, suggests that adolescents require multiple
      points of access to comprehensive, coordinated services, and that preventive
      health interventions must be actively and increasingly integrated across health
      care, school, and community settings. Unless access issues are dealt with in a
      rational, coordinated fashion, America's adolescents will not have access to
      appropriate health services. Current efforts to minimize current health care
      expenditures through managed care programs inevitably conflict with efforts to
      deliver comprehensive preventive services to all adolescents. Use of multiple
      sites may not represent inadequate access to care. However, as managed care
      reimbursement continues to expand, school-based clinics and free-standing
      adolescent health programs increasingly report decreases in reimbursement without
      a change in demand for services. The Office of Technology Assessment study called
      for explicit funding and expansion of services for America's youth; since then, a
      federal Office of Adolescent Health has been authorized, and, by the time this
      reaches print, should have received appropriations and been staffed. Dryfoos has
      called for expansion to nearly 5000 comprehensive programs in the coming years.
      76 Additionally, The Robert Wood Johnson Foundation has just announced a $23.2
      million state-community partnership grant program to increase availability of
      school-based health services for children and youth with unmet health needs.77 As
      health care reform efforts move forward,both careful definition of the services
      adolescents need and adequate financing for these services are essential to
      ensure access to care for all adolescents.

PMID- 8148843
TI  - Preventing lead poisoning in New York City: priorities for lead abatement in
      housing.
AB  - The major challenge for lead poisoning prevention programs is to increase the
      availability of lead-safe housing as quickly as possible. The approach proposed
      by the City of New York maximizes the impact of the limited resources available
      to address this problem. The approach, however, is based on an assumption that in
      the short-term, modest lead hazard reduction measures such as restoring surfaces
      to an intact condition is adequate for most units and that more extensive
      abatement should be reserved for the relatively fewer units in which there is a
      high risk of exposure of lead-poisoned children reside. Ideally, this plan would
      be implemented with voluntary efforts to abate lead hazards when other renovation
      or remodeling occurs or when dwellings are vacant and more extensive abatement
      work can be performed at lower cost and without the attendant difficulty of
      abating occupied units. Approaches ranking hazards and implementing varying
      levels of hazard reduction must be fully evaluated and modified as new
      information becomes available. The specific criteria used to rank hazards should
      be evaluated to determine what measures best differentiate risk. Given the
      magnitude of the problem and the numerous obstacle--lack of funding, limited
      trained workers, and limited technical knowledge--it will probably take years, if
      not decades, to abate lead hazards in all the dwellings in which they exist. We
      must not be deterred, however, from beginning this effort in the communities and
      dwellings that need intervention the most: deteriorated, older housing units in
      which young children reside. In major urban centers such as New York City the
      greatest lead hazards will generally be found in areas where poverty is greatest.
      Thus, every effort must be made to ensure that adequate resources are available
      to improve housing in the communities in greatest need.

PMID- 8148844
TI  - For mother and child: Hadassah in the Holy Land, 1913 through 1993.

PMID- 8148846
TI  - [Methotrexate in rheumatology].

PMID- 8148845
TI  - [Mutation of collagen genes and familial osteoarthritis].

PMID- 8148847
TI  - [Enthesopathy and hyperostosis-osteitis-periostitis syndrome. A nosological
      radioclinical approach to inflammatory spondyloarthropathies].

PMID- 8148848
TI  - [Prevalence of hypothyroidism and hyperthyroidism in temporal arteritis and
      rhizomelic pseudopolyarthritis. A controlled study of 104 cases].
AB  - The aim of this study was to assess the prevalence of hyperthyroidism and
      hypothyroidism in giant cell arteritis and polymyalgia rheumatica. The prevalence
      of thyroid dysfunction in giant cell arteritis and polymyalgia rheumatica
      patients was determined retrospectively from 1976 through 1984 and prospectively
      from 1984 through 1991. A control group was composed of patients over 55 years of
      age consecutively admitted to the same hospital department for another condition.
      Patients were screened for thyroid dysfunction using a thyrotropin assay.
      Abnormal results were evaluated by T3 and T4 assays and, if needed, a TRH test.
      Among the 68 giant cell arteritis patients (mean age 72.6 +/- 7 years), of which
      41 were included in the prospective arm of the study, 6 had hypothyroidism and 3
      had hyperthyroidism. Corresponding figures were 4 and 4 among the 36 patients
      with polymyalgia rheumatica (mean age 71.7 +/- 8.3 years), of which 18 were
      evaluated prospectively. Among the 305 controls (mean age 71.6 +/- 9.4 years), 16
      had hypothyroidism and 10 had hyperthyroidism. Prevalences of hypothyroidism,
      hyperthyroidism, and antithyroid antibodies were not significantly different in
      the control and case groups. Data fail to support previous suggestions that giant
      cell arteritis or polymyalgia rheumatica patients may be an increased risk for
      hypothyroidism or hyperthyroidism. They lend no indirect support to the
      hypothesis that giant cell arteritis and polymyalgia rheumatica may be autoimmune
      disorders.

PMID- 8148849
TI  - [Value of the self-evaluation of functional and painful disorders for the
      differentiation between fibromyalgia and inflammatory rheumatic diseases].
AB  - The authors sought to determine whether the self-report questionnaire developed
      by L.F. Callahan and T. Pincus is of use for the diagnosis of fibromyalgia when
      severe and/or chronic pain raises doubts as to an inflammatory rheumatic disease.
      This questionnaire evaluates the ratio between pain severity assessed on a visual
      analog scale and impairment of activities of daily living. High values suggest
      fibromyalgia, whereas low values occur in rheumatoid arthritis patients. The
      French translation of the questionnaire was completed by 15 fibromyalgia patients
      and 22 patients with inflammatory arthritic syndrome of whom 15 had rheumatoid
      arthritis. Mean pain/impairment ratio was 5.85 +/- 0.68 (SEM) in the fibromyalgia
      group versus 3.01 +/- 0.38 in the inflammatory rheumatism group. This difference
      was highly significant (p = 0.001 by Student's t test). The rheumatoid arthritis
      subgroup was also significantly different from the fibromyalgia group (p =
      0.003). These findings are very similar to those reported by Callahan and Pincus.
      Our data confirm the value of this simple self-evaluation tool. In practice,
      ratios greater than 5 suggest fibromyalgia whereas ratios under 3 support the
      diagnosis of rheumatoid arthritis.

PMID- 8148850
TI  - [Hip dysplasia, a complication of sickle cell anemia].
AB  - Eighty-four hips of sickle cell anemia patients were followed up during adulthood
      after the occurrence during childhood of avascular necrosis of the femoral head.
      Roentgenograms showed residual dysplasia at completion of growth in a substantial
      number of cases: coxa magna was found in 11 hips, coxa plana or loss of capital
      sphericity in 53 hips, and true osteochondritis in 3 hips. Only 20 hips exhibited
      normal morphological features at completion of growth. Anomalies were found not
      only in the proximal femur but also in the acetabulum which was altered in 14
      hips (inadequate lateral coverage in 8 hips and protrusion in 6).
      Roentgenological changes suggested that the acetabular alterations were due to
      triradiate cartilage lesions directly produced by the blood disorder rather than
      to the effects of the femoral alterations. The anomalies seen also suggested that
      the adverse effects of sickle cell anemia on growth involve not only epiphyseal
      ossification centers but also growth plates.

PMID- 8148851
TI  - [Osteoarthritis of limbs in hospital practice in Lome (Togo)].
AB  - Medical records of patients seen at the Lome Teaching Hospital rheumatology
      clinic (Togo) were studied retrospectively to determine the prevalence and
      topographic patterns of osteoarthritis. Among the 2626 patients seen over a three
      year period, 232 had appendicular osteoarthritis. Distribution of affected joints
      was as follows: knee, 212 patients (83% female, 17% male); hip, 17 patients with
      primary osteoarthritis; scapulohumeral joint, 2 patients; and fingers, 1 patient.
      At the knee, the lesions involved the medial femorotibial compartment in 114
      patients, the lateral femorotibial compartment in 54 patients and the
      patellofemoral compartment in 44 patients. Mean age at onset of femorotibial
      osteoarthritis was 50 years. Among females with femorotibial osteoarthritis, 70%
      were obese and 90% had varus or valgus deformities. This study confirms that in
      black Africa the high prevalence of femorotibial osteoarthritis contrasts with
      the low prevalence of primary osteoarthritis of the hip and of osteoarthritis of
      the fingers. Female sex, obesity, and varus or valgus deformities are the main
      risk factors for femorotibial osteoarthritis in black Africa.

PMID- 8148852
TI  - [Common low back pain and vertebral manipulations. Inventory. Evaluation,
      presumptive mechanisms of action. Problems].
AB  - Published data on the efficacy and presumptive modes of action of spinal
      manipulations are reviewed, as well as current problems with the technique.
      Although the best-designed studies have shown promising results, the efficacy of
      spinal manipulations has not as yet been firmly proven. The mode of action may
      involve mechanical changes in the disk and facet joints, but neurological
      mechanisms probably play the key role. Complications of cervical spinal
      manipulations are rare. To protect patients, French law requires that spinal
      manipulations be performed only by licensed physicians, who are the only
      professionals capable of establishing the accurate diagnosis before undertaking
      manipulations.

PMID- 8148853
TI  - [Acquired hemophilia and rheumatoid arthritis. Value of intravenous
      immunoglobulins].
AB  - The authors report an exceedingly rare complication of rheumatoid arthritis, i.e.
      acquired hemophilia due to anti-factor VIII autoantibody production. Treatment
      with intravenous immune globulin ensured control of hemorrhagic manifestations by
      inducing a transient rise in factor VIII level.

PMID- 8148854
TI  - [LP 200mg flurbiprofen versus LP 200mg ketoprofen in rheumatoid arthritis in
      rheumatologic practice].
AB  - A multicentre, randomised, double-blind, double-dummy, parallel-group study in
      outpatients with rheumatoid arthritis compared the efficacy and safety of
      flurbiprofen 200 mg and ketoprofen 200 mg, both in sustained-release form. One
      hundred and sixteen patients aged 18 to 75 years were randomised to receive
      either one capsule of flurbiprofen sustained-release 200 mg (n = 60) or one
      tablet of ketoprofen sustained-release 200 mg (n = 56). Both drugs were taken
      once daily in the evening for 28 days. Patients were assessed at entry and after
      two and four weeks. Overall efficacy as evaluated on a four-point scale by the
      investigator and patient, and overall spontaneous pain as evaluated by the
      patient showed significant improvements in both treatment groups with a trend
      favouring greater benefit with flurbiprofen. Adverse events were recorded in 14
      patients receiving flurbiprofen and 22 patients receiving ketoprofen. Neither the
      incidence nor the type of adverse events were significantly different in the two
      groups. Withdrawal rates for adverse events were very similar with both drugs. In
      conclusion, flurbiprofen sustained-release 200 mg is as effective as ketoprofen
      sustained-release 200 mg in the treatment of symptoms of rheumatoid arthritis,
      and exhibits a comparable safety profile.

PMID- 8148855
TI  - [Algodystrophy of the foot after arterial surgery: microcirculation evaluation].

PMID- 8148856
TI  - [Rapid destructive coxarthritis and Charcot-Marie-Tooth disease. Apropos of 3
      cases].

PMID- 8148857
TI  - [Cervical stabilization with Cotrel-Dubousset equipment in inflammatory rheumatic
      diseases].

PMID- 8148858
TI  - [Diaphyseal Salmonella typhi osteomyelitis. A case].

PMID- 8148859
TI  - [Spontaneous fracture of the femoral neck complicating hip algodystrophy during
      pregnancy. Magnetic resonance imaging].

PMID- 8148860
TI  - [Biological abnormalities in fibromyalgia: a new therapeutic approach?].

PMID- 8148861
TI  - [Rheumatoid factor, subcutaneous nodules and Sjogren's syndrome in rheumatoid
      polyarthritis in Magreb].

PMID- 8148862
TI  - Comparison of a hand-held and fixed dynamometer in measuring strength of patients
      with neuromuscular disease.
AB  - While numerous studies report acceptable reliability of hand-held dynamometers,
      very little information is available on factors affecting measurements and
      comparisons with other force measurement systems. A hand-held dynamometer was
      compared to a fixed dynamometer to determine if the two systems of force
      measurement yielded comparable results. Twenty-one patients with neuromuscular
      disease were measured for maximal isometric strength of 12 muscle groups with
      both force measurement systems using standardized positioning and stabilization
      procedures. Only one of the 12 muscle groups tested demonstrated significantly
      different force measurements between the two systems. Good association was found
      between both systems in force measurements, with Pearson correlation coefficients
      ranging from .76 to .90. We conclude that a hand-held dynamometer and a fixed
      dynamometer yield comparable results in patients with neuromuscular disease,
      provided that testing is limited to muscle groups producing relatively low
      forces.

PMID- 8148863
TI  - Lifting instruction to children in an elementary school.
AB  - Many people have advocated initiating back care education early in life because
      back pain and injuries are so common in the adult population. This study
      investigated the learning of a lifting technique and the risk factors involved in
      low back pain with 27 sixth-grade and 28 eighth-grade public school children. The
      students were instructed through verbal presentation, demonstration, and a
      practice session. Student performance was assessed with multiple choice tests and
      practical performance tests. Testing was administered prior to instruction, 2
      days after instruction, and 6-7 weeks after instruction. There was a
      statistically significant improvement (p < 0.05) in all postinstruction scores
      compared with preinstruction scores in both the multiple choice and practical
      performance tests for both grade levels. The effectiveness of a brief
      instructional session on some back care education principles to children was
      demonstrated. Preventive intervention programs with children could be easily
      implemented in elementary school systems. The long-term outcome of such programs
      needs to be evaluated.

PMID- 8148864
TI  - Are "passive" extension exercises really passive?
AB  - When rehabilitating patients with back dysfunction, extension exercises that are
      presumably "passive" for the erector spinae muscles are frequently used. The
      purpose of this study was to record electromyographic (EMG) activity from back
      extensor muscles to determine if these muscles are truly inactive during these
      maneuvers. Surface EMG was recorded bilaterally from lower lumbar muscles in 62
      pain-free subjects. The root-mean-square EMG activity, recorded in microV, for
      the four positions tested was (mean +/- SD): lying prone (1.268 +/- 0.902),
      extension in lying prone (6.713 +/- 6.976), standing neutral (4.760 +/- 3.282),
      and extension in standing (3.558 +/- 2.273). One-way ANOVA for repeated measures
      and Tukey's post hoc test were used to analyze the data. The results indicated
      that EMG activity was greatest for extension in lying prone (p < .05), equivalent
      between the two standing positions (p > .05), and least when lying prone (p <
      .05). The results of this study demonstrated that "passive" extension exercises
      were not truly passive for lumbar back extensor muscles. From a clinical
      perspective, if the performance of passive back extension is important, extension
      in lying prone may not be the exercise of choice and having patients lying prone
      may be the most beneficial.

PMID- 8148865
TI  - Referred knee pain in a young athlete: a case study.
AB  - Parapatellar pain is a common complaint in the active adolescent patient
      population. Patello-femoral pain syndrome, Osgood-Schlatter disease, Sinding
      Larsen-Johansson syndrome, patellar tendinitis, and other stress failure
      conditions are the primary causes of these parapatellar symptoms. Not all cases
      of knee discomfort are related to knee pathology. This case study discusses hip
      pathology as a source of referred knee pain in an 8-year-old male athlete. Care
      must be taken to evaluate all possible sources of both primary and referred pain
      in all cases.

PMID- 8148866
TI  - Injury in ballet: a review of relevant topics for the physical therapist.
AB  - Currently, there is a need for a review of the literature on ballet injury as it
      pertains to the physical therapist. Relatively few articles have reviewed ballet
      injury prevalence and mechanisms of injury. The purpose of this paper was to
      provide a thorough literature review of the prevalence of ballet injury and
      mechanisms of injury. Environmental factors and footwear relating to ballet
      injury were also reviewed. The literature indicated that 65-80% of ballet
      injuries are in the lower extremity, 10-17% occur in the vertebral column, and
      most of the remaining percentage are upper limb injuries (5-15%). The etiology of
      common lower limb conditions included an incorrect turnout; soft tissue
      imbalances; reduced quadriceps performance; "rolling in of the foot;" inversion
      sprains; and frequent plies, pointe, and demipointe work. Spinal conditions were
      reported to result from hyperextension and hyperlordosis of the lumbar spine as
      well as the psoas insufficiency syndrome. It was revealed that inappropriately
      fitting footwear lead to various foot conditions and abnormal lower kinetic chain
      biomechanics. Environmental factors, such as the dance surface, also have
      implications in ballet injury. The author concluded that ballet injuries have a
      multifactorial etiology that primarily involves the interplay of compensatory
      biomechanics in the spine and lower extremity, environmental factors, and
      footwear. In addition, some clinical recommendations have been made regarding the
      physical therapy management of ballet injuries.

PMID- 8148867
TI  - Rehabilitation parameters in total knee replacement patients undergoing epidural
      vs. conventional analgesia.
AB  - Epidural analgesia for total knee replacement (TKR) surgery has been proposed as
      a means of enhancing patient comfort, thereby expediting rehabilitation and
      reducing hospital stay. This study was done to determine differences in
      rehabilitation parameters of range of motion and mobility in patients receiving
      epidural vs. conventional (intravenous) analgesia following TKR surgery. Chart
      reviews were done of 52 patients who underwent consecutive unilateral TKR, with
      26 patients in each analgesia group. There were 21 males and 31 females, ages 24
      88 years (median 65), with diagnoses of osteoarthritis (45), rheumatoid arthritis
      (4), and other (3). The surgeon, procedure, type of prosthesis, and physical
      therapy protocol were the same for all subjects. Demographics, range of motion,
      distance walked, assistance required for gait and transfers, assistive device,
      and exercise competence data were studied at the first postoperative day and at
      time of discharge. No significant difference was found in the length of stay at
      the p < .05 level. Significant differences at the first postoperative day favored
      the epidural group: in knee flexion range--median difference was 0.26 rad [95%
      confidence interval (CI): 0.09-0.52, p < .05] ie., 15 degrees (95% CI: 5-30); in
      total range of motion--median difference was 0.30 rad (95% CI: 0.09-0.58, p <
      .05), ie., 17 degrees (95% CI: 5-33); and in assistance required for gait and
      transfers (p < .05). At discharge, the epidural group required significantly less
      assistance (p < .05). There was a trend toward greater walking distance in the
      epidural group, who walked a median of 15.2 m farther than the conventional
      analgesia group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8148868
TI  - The effects of athletic massage on delayed onset muscle soreness, creatine
      kinase, and neutrophil count: a preliminary report.
AB  - It was hypothesized that athletic massage administered 2 hours after eccentric
      exercise would disrupt an initial crucial event in acute inflammation, the
      accumulation of neutrophils. This would result in a diminished inflammatory
      response and a concomitant reduction in delayed onset muscle soreness (DOMS) and
      serum creatine kinase (CK). Untrained males were randomly assigned to a massage
      (N = 7) or control (N = 7) group. All performed five sets of isokinetic eccentric
      exercise of the elbow flexors and extensors. Two hours after exercise, massage
      subjects received a 30-minute athletic massage; control subjects rested. Delayed
      onset muscle soreness and CK were assessed before exercise and at 8, 24, 48, 72,
      96, and 120 hours after exercise. Circulating neutrophils were assessed before
      and immediately after exercise, and at 30-minute intervals for 8 hours; cortisol
      was assessed before and immediately after exercise, and at 30-minute intervals
      for 8 hours; cortisol was assessed at similar times. A trend analysis revealed a
      significant (p < 0.05) treatment by time interaction effect for 1) DOMS, with the
      massage group reporting reduced levels; 2) CK, with the massage group displaying
      reduced levels; 3) neutrophils, with the massage group displaying a prolonged
      elevation; and 4) cortisol, with the massage group showing a diminished diurnal
      reduction. The results of this study suggest that sports massage will reduce DOMS
      and CK when administered 2 hours after the termination of eccentric exercise.
      This may be due to a reduced emigration of neutrophils and/or higher levels of
      serum cortisol.

PMID- 8148869
TI  - Mouse dioxin-inducible cytosolic aldehyde dehydrogenase-3: AHD4 cDNA sequence,
      genetic mapping, and differences in mRNA levels.
AB  - We have cloned and sequenced the murine AHD4 cDNA encoding the 'Class 3'
      cytosolic aldehyde dehydrogenase (ALDH-3c). The cDNA is 1722 bp in length,
      excluding the poly(A+) tail, and has 5' and 3' nontranslated regions of 174 bp
      and 186 bp, respectively. AHD4 encodes a protein of 453 amino acids, including
      the first methionine (M(r) = 50,466). The murine AHD4 protein is 91% and 80%
      similar to the rat and human ALDH3c proteins, respectively, 64% identical to the
      rat microsomal ALDH3 protein, and < 28% similar to ALDH 'Class 1' and 'Class 2'
      proteins. Surprisingly, in contrast to the rat gene that is expressed in both
      cell cultures and the intact liver, the murine Ahd-4 gene is inducible by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD; dioxin) or benzo[a]pyrene in cell cultures but
      not in liver of the intact adult or newborn mouse. Southern hybridization
      analysis of mouse DNA probed with the full-length cDNA reveals that the Ahd-4
      gene is likely to span less than a total of 15 kb, and was mapped to chromosome
      (Chr) 11 between the Mgat-1 and Shbg loci by analysis of two multilocus crosses.
      AHD4 mRNA levels are strikingly elevated in the untreated mouse hepatoma Hepa
      1c1c7 mutant line c37 lacking CYP1A1 (aryl hydrocarbon hydroxylase) activity and
      in the untreated 14CoS/14CoS mouse cell line having a homozygous deletion of
      about 1.2 cM on Chr 7. Our data suggest that the Ahd-4 gene in murine cell
      cultures is regulated by three distinct mechanisms: Ah receptor-mediated
      induction by TCDD or benzo[a]pyrene, CYP1A1 metabolism-dependent repression, and
      Chr 7-mediated putative derepression.

PMID- 8148870
TI  - Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of
      human CYP2C in N-demethylation in the substrate concentration-dependent manner.
AB  - Metabolism of diazepam (DZP) was studied in vitro to clarify the involvement of
      different forms of hepatic cytochrome P450 (CYP) in rats, and humans of Japanese
      and Caucasian origin. Microsomal 3-hydroxylation was the major pathway of DZP
      metabolism in rats and was inhibited by anti-CYP3A antibodies. Purified CYP3As
      and CYP2C11 catalysed 3-hydroxylation and N-demethylation, respectively, in the
      reconstituted systems. The rates of both reactions in human liver microsomes
      depended on the substrate concentration: the rate of 3-hydroxylation was 3-4
      times higher than N-demethylation at 0.2 mM; the two activities were essentially
      the same at a lower substrate concentration (0.02 mM). Inhibitions of the N
      demethylation by anti-CYP2C antibody and S-mephenytoin also depended on the
      substrate concentration and was detectable only at a low substrate concentration.
      Kinetic studies revealed the presence of two distinct catalytic activities for
      the N-demethylation; low Km and low Vmax, and high Km and high Vmax. The former
      activity seems to be mediated by a CYP2C P450 form. On the other hand, DZP 3
      hydroxylation was rather selectively catalysed by a CYP3A P450 at the low and
      high substrate concentrations. These results were consistent with the observation
      in vivo that DZP N-demethylation and S-mephenytoin 4'-hydroxylation are closely
      correlated in humans. These results also suggest that the apparent discrepancy on
      the role of CYP forms in DZP metabolism in vitro and in vivo may reside in the
      difference in substrate concentration.

PMID- 8148871
TI  - Beeturia and the biological fate of beetroot pigments.
AB  - Beeturia, the passage of pink or red urine after the ingestion of beetroot, is
      said to occur in 10-14% of the population, and is more common in iron deficiency
      and malabsorption. A specific HPLC assay for betacyanins, the red beetroot
      pigments, in biological fluids was developed to study the prevalence of this
      apparent polymorphism in humans, and to investigate its basis in rats. Two major
      peaks were observed in chromatograms of extracts of unpickled beetroot. They had
      identical UV absorption spectra (lambda max = 535 nm) by diode array analysis,
      and mass spectrometry indicated that one (betacyanin 1) was betanin or its epimer
      and the other (betacyanin 2) a disaccharide of betacyanin 1. In a population of
      100 normal subjects the 0-8 h urinary recoveries after an oral dose of 60 mg
      beetroot extract were 0.06-0.54% for betacyanin 1 and 0.01-0.6% for betacyanin 2.
      The distributions of these data were skewed but not clearly bimodal by visual
      inspection or by kernel density analysis. Four subjects produced visibly red
      urine and had betacyanin recoveries at the upper end of the population range.
      Studies using in situ isolated perfused rat jejunum and liver preparations
      indicated a negligible absorption of the pigments after 1 h and no detectable
      metabolism or biliary secretion. Intact anaesthetized rats given i.v. bolus doses
      of beetroot extract cleared both betacyanins from plasma at the rate of 3.3 +/-
      0.9 (SD) ml min-1 (n = 5). The total urinary recovery of both pigments amounted
      to 80% of the dose, and their renal clearances approached their plasma
      clearances. These data suggest that beeturia does not arise from deficiencies in
      hepatic metabolism or renal excretion of betacyanins. After oral administration
      of beetroot extract to rats the betacyanin content of the stomach decreased
      rapidly with time but neither the intestines nor the bile duct were stained
      visibly red. These findings together with those showing instability of the
      betacyanins in acid conditions suggest that variability in the biological fate of
      beetroot pigments may be determined largely by gastric pH and emptying rate.

PMID- 8148872
TI  - Ten nucleotide differences, five of which cause amino acid changes, are
      associated with the Ah receptor locus polymorphism of C57BL/6 and DBA/2 mice.
AB  - We have analysed by heteroduplex formation (HF), single stranded conformational
      polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), and
      nucleotide sequencing the cDNAs of the Ahrb-1 and Ahrd allelic forms of the
      aromatic hydrocarbon receptor (AhR) present in inbred strains of mice. The Ahrb-1
      allele, found in the C57BL and C57BR strains, encodes a 95 kDa receptor with an
      affinity for ligand 15-20 times higher than the affinity of the 104 kDa receptor
      encoded by the Ahrd allele, found in the DBA/2 strain. Five overlapping fragments
      of the AhR coding sequence were obtained from liver RNA by reverse transcriptase
      synthesis of a cDNA first strand, followed by polymerase chain reaction
      amplification of these cDNA sequences (RT-PCR). Analysis by HF and SSCP revealed
      the presence of sequence differences in three of the five fragments. When the
      complete nucleotide sequence of the coding regions was determined by PCR
      sequencing, we found a total of ten nucleotide differences between the two
      alleles, nine of which localized to the three fragments where differences were
      detected by HF and SSCP. Five of the differences are silent. Of the other five,
      one changes the opal termination codon in Ahrb-1 to the codon for Arg in Ahrd,
      extending translation of the mRNA by 43 amino acids and accounting for the larger
      size of the AhR peptide in DBA/2 mice. One of the four remaining differences
      causes the replacement of a leucine residue in Ahrb-1 by a proline residue in
      Ahrd, and breaks a potential alpha-helix near the AhR Q-rich region; it is likely
      that structural changes associated with this amino acid change are responsible
      for the differences in agonist affinity observed between the Ah receptors of
      these two strains of mice.

PMID- 8148873
TI  - Relationship of CYP2D6 (debrisoquine hydroxylase) genotype to breast cancer
      susceptibility.

PMID- 8148874
TI  - Polymorphic N-acetyltransferase (NAT2) in Amerindian populations of Panama and
      Colombia: high frequencies of point mutation 857A, as found in allele S3/M3.

PMID- 8148875
TI  - Extensin: repetitive motifs, functional sites, post-translational codes, and
      phylogeny.
AB  - Homologous hydroxyproline-rich glycoproteins (HRGPs) of the plant extracellular
      matrix include extensins, repetitive proline-rich proteins (RPRPs), some
      nodulins, gum arabic glycoprotein (GAGP), arabinogalactan-proteins (AGPs), and
      chimeric proteins such as potato lectin which contain an extensin module fused to
      a lectin. The key to the role of HRGPs in cell wall self-assembly and cell
      extension lies in their chemistry, which is dependent on extensive post
      translational modifications (PTMs): hydroxylation, glycosylation, and cross
      linking. Repetitive peptide motifs characterize HRGPs. One or more repetitive
      peptide motifs and their variants, singly or in combination, may constitute
      functional sites involved in various aspects of cell wall assembly, as follows:
      (i) X-Hypn including Ser-Hyp4 (arabinosylation site, molecular rigidity, and
      reptation). (ii) Pro-Hyp-Val-Tyr-Lys and variants (putative intermolecular cross
      links, adhesion, cohesion, and possible beta-turns). (iii) Tyr-X-Tyr-Lys
      (intramolecular isodityrosine [IDT] cross-links increase molecular rigidity and
      hydrophobicity). (iv) (Glyco)peptide palindromes (centrosymmetric domains:
      putative self-assembly nucleation sites). (v) Ionic interaction sites (protein
      protein and protein-carbohydrate cross-links). (vi) Hyp and Ser glycosylation
      sites (enhance conformational stability and molecular recognition). (vii)
      Extensin modules in chimeric proteins (e.g. solanaceous lectins). Rules for the
      post-translational modifications are emerging: (i) Hydroxylation of proline
      residues may depend on multiple, sequence-specific prolyl hydroxylases rather
      than on a single (polyproline-II) conformation-dependent enzyme. Furthermore, Lys
      Pro, Tyr-Pro, and Phe-Pro are not hydroxylated, while Pro-Val is always. (ii)
      Contiguity of Hyp residues probably determines the extent of Hyp glycosylation,
      blocks of tetrahydroxyproline (Hyp4) being the most highly arabinosylated, while
      single non-contiguous Hyp residues are rarely arabinosylated, although they are
      likely attachment sites for the larger arabinogalactan substituents of gum arabic
      glycoprotein and arabinogalactan-proteins. (iii) While intramolecular cross-links
      involve IDT, unidentified intermolecular cross-links most likely involve the Val
      Tyr-Lys motif (perhaps also Val-Lys-Pro-Tyr-His-Pro), probably as an adduct
      between Tyr and Lys catalyzed in vitro by a pI 4.6 extensin cross-linking
      peroxidase. Thus, we can classify HRGPs functionally as either cross-linking or
      non-cross-linking, i.e. CL- or NCL-extensins. Their protistan origin obscures the
      phylogenetic affinities of a single extensin-HRGP family due to their sequence
      divergence. We propose a phylogenetic series ranging from the minimally
      glycosylated basic RPRPs to the highly glycosylated acidic AGPs. Furthermore,
      based on similarities between dicots and gymnosperm extensins, and their marked
      difference from graminaceous monocot extensins, graminaceous monocot and dicot
      lines may have diverged as early as the progymnosperms.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8148876
TI  - Pokeweed antiviral protein inactivates pokeweed ribosomes; implications for the
      antiviral mechanism.
AB  - Pokeweed antiviral protein (PAP) and other ribosome-inactivating proteins (RIPs)
      had previously been thought to be incapable of attacking conspecific ribosomes,
      thus having no effect on endogenous processes. This assertion conflicts with a
      model for PAP's in vivo antiviral mechanism in which PAP (a cell wall protein)
      selectively enters virus-infected cells and disrupts protein synthesis, thus
      causing local suicide and preventing virus replication. We show here that
      pokeweed (Phytolacca americana) ribosomes, as well as endod (Phytolacca
      dodecandra) ribosomes, are indeed highly sensitive to inactivation by conspecific
      RIPs. Ribosomes isolated from RIP-free pokeweed and endod suspension culture
      cells were found to be highly active in vitro, as measured by poly(U)-directed
      polyphenylalanine synthesis. Phytolacca ribosomes challenged with conspecific
      RIPs generated dose-response curves (IC50 of 1 nM PAP or dodecandrin) very
      similar to those from wheat germ ribosomes. To determine if Phytolacca cells
      produce a cytosolic 'anti-RIP' protective element, ribosomes were combined with
      Phytolacca postribosomal supernatant factors from culture cells, then challenged
      with conspecific RIPs. Resulting IC50 values of 3-7 nM PAP, PAP-II, PAP-S or
      dodecandrin indicate that supernatants from these Phytolacca cells lack a
      ribosomal protective element. This research demonstrates that PAP inactivates
      pokeweed ribosomes (and is therefore potentially toxic to pokeweed cells) and
      supports the local suicide model for PAP's in vivo antiviral mechanism. The
      importance of spatial separation between PAP and ribosomes of cells producing
      this RIP is emphasized, particularly if crop plants are transformed with the PAP
      gene to confer antiviral protection.

PMID- 8148877
TI  - The basic domain in the bZIP regulatory protein Opaque2 serves two independent
      functions: DNA binding and nuclear localization.
AB  - For organisms to grow and develop, transcriptional regulatory proteins must
      localize to the nucleus. This movement is mediated by nuclear localization
      sequences (NLSs) which consist of short stretches of basic amino acids that are
      part of the structure of mature nuclear proteins. Two NLSs have been previously
      identified in the maize regulatory protein Opaque2 (O2), a member of the basic
      domain, leucine-zipper (bZIP) class of proteins. In this report, it has been
      determined that both of these NLSs are necessary for import of O2, and the focus
      has been on a functional analysis of the more efficient, bipartite NLS that is
      present in the basic or DNA-binding domain. A mutation which contains altered
      amino acids on both parts of this NLS severely reduced nuclear targeting, and led
      to the definition of two classes of bipartite NLSs. Since the bipartite NLS is
      located in the highly conserved. DNA-binding domain, the dual role of this domain
      was examined using the maize mutant o2-676, in which a conservative mutation
      eliminates the DNA-binding function. The o2-676 protein localized to the nucleus
      in maize and the bZIP domain from the mutant protein was sufficient to redirect a
      reporter protein to the nucleus in transgenic plant cells. Thus, it was possible
      to show that the nuclear targeting function of this domain is independent of DNA
      binding. Sequence conservation of the basic domain of other bZIP proteins
      suggests that the bifunctionality of this domain may be conserved in all members
      of this class; a consensus sequence for a bipartite NLS in bZIP proteins is
      suggested.

PMID- 8148878
TI  - Cloning and in vivo expression of functional triose phosphate/phosphate
      translocators from C3- and C4-plants: evidence for the putative participation of
      specific amino acid residues in the recognition of phosphoenolpyruvate.
AB  - The primary sequences of the chloroplast triose phosphate/phosphate translocator
      precursor proteins from C4-plants (maize mesophyll cells and Flaveria trinervia)
      and from the C3-type Flaveria pringlei were determined. The mature parts of these
      translocators possess 83-94% identical amino acid residues. The C4-translocator
      protein can be correctly targeted to C3-type chloroplasts and inserted into the
      envelope membrane. Expression of the mature parts of these chloroplast
      translocators (cTPT) in transformed yeast cells and subsequent reconstitution of
      the functional proteins reveals the difference between the recombinant
      translocator proteins from the two cell types with respect to the transport of
      phosphoenolpyruvate. Comparison of the cTPT sequences from F. pringlei and F.
      trinervia in combination with computer-aided molecular modelling of the substrate
      translocation pore leads to the suggestion, that only minor exchanges of amino
      acid residues between the C3- and C4-translocator proteins are sufficient to
      extend their substrate specificities to recognize also phosphoenolpyruvate.

PMID- 8148879
TI  - The psaA operon pre-mRNA of the Euglena gracilis chloroplast is processed into
      photosystem I and II mRNAs that accumulate differentially depending on the
      conditions of cell growth.
AB  - The chloroplast genome of Euglena gracilis contains a psaA operon which encodes a
      lysine tRNA gene, trnK; psaA and psaB photosystem I genes, and psbE, psbF, psbL
      and psbJ photosystem II genes. The pre-mRNA of the psaA operon undergoes a
      complex processing pathway of 5' and 3' tRNA processing, splicing of 11 group II
      introns and one group II twintron, plus three intercistronic RNA cleavage events.
      The accumulated transcripts of the psaA operon have been characterized by
      Northern hybridization, S1 nuclease analysis and primer extension RNA sequencing.
      The mature 5' end of the psaA-psaB-psbE-psbF-psbL-psbJ hexacistronic transcript
      lies 8 nt downstream of the trnK gene, and is the result of intercistronic trnK
      psaA cleavage. Other intercistronic processing events occur between the psaA and
      psaB genes and the psaB and psbE genes. Processing at the latter site produces a
      dicistronic mRNA of PSI genes and a tetracistronic mRNA of PSII genes. The PSI
      dicistronic transcript is further processed to monocistronic psaA and psaB mRNAs.
      Secondary structural motifs within the intercistronic regions may be recognition
      sites for processing. The steady-state levels of psaA operon mRNAs from Euglena
      grown under several different conditions have been determined. Accumulated
      transcripts from all growth conditions are spliced, and a proportion are also
      processed at the intercistronic sites. The products of intercistronic processing
      increase from heterotrophic dark- to heterotrophic light-grown Euglena, and from
      heterotrophic light- to photoautotrophic light-grown Euglena. The differential
      accumulation of psaA operon mRNAs may be a means of chloroplast gene regulation
      or, alternatively, a consequence of gene expression during chloroplast
      development.

PMID- 8148880
TI  - Transgenic complementation of the hy3 phytochrome B mutation and response to PHYB
      gene copy number in Arabidopsis.
AB  - A recombinant PHYB minigene (mPHYB) consisting of the complete Arabidopsis PHYB
      cDNA sequence fused to 2.3 kb of upstream PHYB promoter sequence has been
      introduced into wild-type Arabidopsis and into a strain containing the Bo64
      allele of the hy3 mutation. The Bo64 mutant has previously been shown to contain
      a nonsense mutation in the PHYB coding sequence. Transformation of this strain
      with the mPHYB gene results in complementation of all of the mutant phenotypic
      characteristics tested including hypocotyl length and hypocotyl cell size,
      response to end-of-day far-red light, leaf morphology, chlorophyll level, and
      flowering time. Presence of the mPHYB transgene in a wild-type genetic background
      causes exaggeration of this same set of phenotypic characteristics, indicating
      that these diverse photo-morphogenic responses are sensitive to the copy number
      of the PHYB gene. The transgene inserts in the Bo64(mPHYB) and WT(mPHYB) lines
      are shown to be single locus and single copy and the immunologically detectable
      level of phytochrome B is shown to vary linearly with PHYB gene copy number.
      These results demonstrate a complex role for phytochrome B in Arabidopsis photo
      morphogenesis and suggest that the expression level of this phytochrome gene is
      an important determinant of the intensity of light-induced plant responses.

PMID- 8148881
TI  - Fertile transgenic wheat from microprojectile bombardment of scutellar tissue.
AB  - A reproducible transformation system for hexaploid wheat was developed based on
      particle bombardment of scutellar tissue of immature embryos. Particle
      bombardment was carried out using a PDS 1000/He gun. Plant material was bombarded
      with the plasmid pDB1 containing the beta-glucuronidase gene (uidA) under the
      control of the actin-1 promoter of rice, and the selectable marker gene bar
      (phosphinothricin acetyltransferase) under the control of the CaMV 35S promoter.
      Selection was carried out using the herbicide Basta (Glufosinate-ammonium). From
      a total number of 1050 bombarded immature embryos, in seven independent
      transformation experiments, 59 plants could be regenerated. Putative
      transformants were screened for enzyme activity by the histochemical GUS assay
      using cut leaf material and by spraying the whole plants with an aqueous solution
      of the herbicide Basta. Twelve regenerants survived Basta spraying and showed GUS
      activity. Southern-blot analysis indicated the presence of introduced foreign
      genes in the genomic DNA of the transformants and both marker genes were present
      in all plants analysed. To date, four plants have been grown to maturity and set
      seed. Histochemically stained pollen grains showed a 1:1 segregation of the uidA
      gene in all plants tested. A 3:1 segregation of the introduced genes was
      demonstrated by enzyme activity tests and Southern blot analysis of R1 plants.

PMID- 8148882
TI  - Capital concerns. Financial reporting, corporate cultures challenges to
      integrated health systems.

PMID- 8148883
TI  - Blue Hill's odyssey. Our goal: to be a prototype for rural primary care.
      Interview by Kevin Lumsdon.
AB  - When Bruce Cummings was recruited for the CEO post at Blue Hill (ME) Memorial
      Hospital, the organization was still reeling from a dispute that had led the
      medical staff to declare a vote of no confidence in the former administration and
      board of directors. Cummings has since guided the medical staff and board through
      discussions that culminated in a new vision: forming an integrated primary care
      system. That redirection earned Blue Hill honors as a finalist earlier this year
      in the American Hospital Association's first NOVA awards for collaboration.
      Cummings spoke recently with senior editor Kevin Lumsdon about the hospital's
      plans.

PMID- 8148884
TI  - Changing course. Realigning the supply chain: providers & suppliers share risks,
      rewards.
AB  - The term "partnership" is overused these days, but health care providers and
      suppliers are taking it seriously, forging new kinds of relationships. A new
      Hospitals & Health Networks survey documents the approaches suppliers are taking
      in response to reform and other health system changes. In fact, a strong majority
      of suppliers are working with their clients now to realign the supply chain, and
      redefining the concept of value in the process.

PMID- 8148885
TI  - State laws: a stumbling block for systems integration?
AB  - Health care providers and insurers moving to form networks face a raft of state
      regulations on the purchase of equipment or the addition of new services,
      selective contracting, the hiring of physicians, referral practices and
      licensure. Two of these of regulations, the "any-willing-provider" laws and
      certificate-of-need laws, are making headlines in some states.

PMID- 8148886
TI  - Hitting the mark. Benchmarking: management tool in the quest for improved
      clinical quality.

PMID- 8148887
TI  - Resolving conflict the right way.

PMID- 8148888
TI  - Atlanta. Managed care heats up competition among payers and providers.

PMID- 8148889
TI  - Data watch. Rural and primary care across the nation.

PMID- 8148890
TI  - Getting real: study finds success factors in patient education.

PMID- 8148891
TI  - Student program spurs generalism at medical schools.

PMID- 8148892
TI  - Who's responsible? Resolving provider and public differences.

PMID- 8148893
TI  - Curing workers' compensation woes.

PMID- 8148894
TI  - Tools for the road ahead.

PMID- 8148895
TI  - Gestational diabetes: a nearly normal pregnancy.

PMID- 8148896
TI  - Jessica's story.

PMID- 8148897
TI  - Balinese birth.

PMID- 8148898
TI  - Roller coaster ride.

PMID- 8148899
TI  - Loss of a homebirth dream.

PMID- 8148900
TI  - A plea for compassionate care.

PMID- 8148901
TI  - Miscarriage at home.

PMID- 8148903
TI  - They built midwives homes.

PMID- 8148902
TI  - Tea for two.

PMID- 8148904
TI  - Heart attack!

PMID- 8148905
TI  - A healing year.

PMID- 8148906
TI  - Midwives on line.

PMID- 8148907
TI  - In the daily waterfall of tears.

PMID- 8148908
TI  - Life is, as birth often is, an unexpected outcome.

PMID- 8148909
TI  - When one of us dies.

PMID- 8148910
TI  - A painful road.

PMID- 8148911
TI  - Second-guessing an unexpected outcome.

PMID- 8148913
TI  - Breastfeeding: food for thought.

PMID- 8148912
TI  - A father's metamorphosis.

PMID- 8148914
TI  - Finger-feeding a preemie.

PMID- 8148915
TI  - A short term disability.

PMID- 8148916
TI  - The good oil.

PMID- 8148917
TI  - Elegy for country hospitals.

PMID- 8148918
TI  - Strikes gain political favour.

PMID- 8148919
TI  - A little help with the law. Interview by Kathy Stodart.

PMID- 8148920
TI  - Putting Peplau to work.

PMID- 8148921
TI  - Developing standards.

PMID- 8148922
TI  - Keeping it private.

PMID- 8148923
TI  - The impact of five-month basic military training on the body weight and body fat
      of 197 moderately to severely obese Singaporean males aged 17 to 19 years.
AB  - The impact of five-month basic military training on body weight and fat mass was
      studied in 197 male obese recruits, aged 17 to 19 years old. The training
      programme of five days per week lasted for 20 weeks. Of these sessions, 57% could
      be considered to be physically intense for the obese subjects. No dietary
      restriction was imposed. The cohort was divided into three categories based on
      their percentage body fat, i.e. %BF 24 to < 30, %BF 30 to < 35 and %BF > or = 35.
      The overall mean weight loss was 12.5 kg or 0.63 kg per week. Mean weight losses
      for each category were 10.7 kg, 13.1 kg and 16.1 kg, respectively. Most of this
      weight was lost in the 2nd month of training. The weight loss is attributed to a
      decrease of body fat as determined by skinfold measurements. Attrition rate, due
      to training injuries resulting in temporary disabilities, was negligible at 6.1%.
      In conclusion, this study shows that intense physical activity over a duration of
      20 weeks is effective in reducing the body fat of our obese subjects and in
      training obese subjects for combat duties.

PMID- 8148924
TI  - Glycemic thresholds for hypoglycemic responses in obese subjects.
AB  - The objective of this study was to compare glycemic thresholds for hypoglycemic
      responses in obese and control subjects. A modified glucose-clamp technique was
      used to produce a standardized fall in plasma glucose (0.5 mmol/l per 40 min) in
      nine morbidly obese and ten control subjects. The release of the counter
      regulatory hormones was measured and a symptom questionnaire was filled out every
      10 min. The hypoglycemic thresholds (taken as the plasma glucose level where the
      response exceeded the basal level +2 s.d.) were practically identical in the two
      groups both for the hormones and the symptoms (including hunger). Our results
      argue against the hypothesis that an increased sensitivity to a falling plasma
      glucose is of importance in the pathogenesis of obesity.

PMID- 8148925
TI  - The effect of adiposity on children's left ventricular mass and geometry and
      haemodynamic responses to stress.
AB  - This study evaluated the relationship between adiposity, left ventricular mass
      and geometry, and haemodynamic parameters at rest and during laboratory stressors
      in a sample of 69 normotensive children with positive family histories of
      essential hypertension. Children were classified as overweight if they were above
      the 85th percentile of weight-for-height for their age and gender compared to
      national normative data. Nineteen children (7 whites, 12 blacks) were classified
      as overweight and the remaining 50 (26 whites, 24 blacks) were not overweight.
      Overweight children were found to have higher resting systolic and diastolic
      blood pressures, heart rates (HR), cardiac output (CO) and stroke volumes (SV),
      and lower resting total peripheral resistance than the non-overweight children.
      No differences were noted in haemodynamic reactivity to the stressors.
      Echocardiographic findings indicated that the overweight children had greater
      left ventricular mass indexed by height2.7, interventricular septal thickness and
      left ventricular end diastolic diameter (LVEDD) compared to non-overweight
      children. These findings are the first to indicate that the higher resting
      pressures of overweight normotensive children are a reflection of increased
      normotensive children are a reflection of increased preload (i.e. greater HR, SV,
      CO, LVEDD). These findings point out the early deleterious effects of obesity on
      the cardiovascular system in the young and highlight the need for effective
      obesity prevention and intervention programmes.

PMID- 8148926
TI  - Plasma cholecystokinin and pancreatic polypeptide secretion in response to
      bombesin, meal ingestion and modified sham feeding in lean and obese persons.
AB  - Disturbed satiety mechanisms may contribute to obesity. There has been
      speculation that cholecystokinin (CCK) and pancreatic polypeptide (PP) are
      involved in the regulation of satiety. We have therefore investigated whether
      there are differences between healthy lean and healthy non-diabetic obese
      volunteers in plasma CCK or PP release after a neuropeptidergic stimulation with
      bombesin and after infusion of a mixed meal. There were no differences in plasma
      CCK between groups either basally or in response to either form of stimulation.
      However, the plasma PP concentrations after the meal were significantly less in
      obese (2845 +/- 404 pM.min) than in lean subjects (5569 +/- 997 pM.min), whereas
      the plasma PP concentrations during bombesin were similar in both groups. We
      tested two other groups of nine obese and lean subjects to determine whether a
      disturbed vagal function could be the cause of the diminished plasma PP in obese
      persons, by studying the effect of modified sham feeding (MSF) on plasma PP.
      However, there were no significant differences in the plasma PP response to MSF
      between lean and obese subjects. We conclude that there are no differences
      between lean and obese persons in plasma CCK secretion in response to infusion of
      the neuropeptide bombesin or to ingestion of a mixed meal. However, the plasma PP
      after a mixed meal, is markedly diminished in obese subjects. This could not be
      attributed to a disturbed vagal cephalic stimulation.

PMID- 8148927
TI  - Ethnic differences in indices of body mass and body fat distribution in Israel.
AB  - Ethnic differences in cardiovascular disease have been demonstrated in the Jewish
      population in Israel. Different measures of body fat have been shown to be
      directly and indirectly associated with increased risk of cardiovascular disease.
      It is not known to what extent lifestyle and genetic factors contribute to the
      distribution of body fat. The aim of this study was to examine ethnic differences
      in the distribution of body fat among Israelis. Between 1985 and 1989, a sample
      of 2154 males and 1395 females employed in Israeli industry were screened for
      selected risk factors for cardiovascular disease, in the framework of the Israel
      CORDIS study. Anthropometric measurements included height, weight, three
      circumferences (waist, hip, chest) and two skinfolds (subscapular and triceps
      skinfolds). In univariate analysis of six anthropometric variables, highly
      significant differences (P < 0.001) between ethnic groups were found in both
      sexes. The subjects of European origin had the highest amount of fat in the upper
      part of the body (WHR) for both sexes. After adjustment for factors such as
      cigarette smoking, education and sporting activity, the discrimination between
      ethnic groups remained statistically significant (P < 0.001) for all
      anthropometric indices except the triceps skinfold. Body mass index was not the
      best discriminating variable. Chest-to-waist ratio was the most powerful
      discriminator in males, but the subscapular-to-triceps ratio was the most
      powerful in females. These findings suggest that differences in body fat
      distribution are derived from both genetic and lifestyle factors.

PMID- 8148928
TI  - Adipose tissue density, estimated adipose lipid fraction and whole body adiposity
      in male cadavers.
AB  - Lipid and water together typically make up more than 90% of the body's adipose
      tissue mass. Although some reports have shown that the fraction of lipid in
      adipose tissue is greater in obese people than in lean ones, the quantitative
      relationship between adipose lipid fraction and overall adiposity of the body has
      never been investigated. We dissected six male unembalmed cadavers and weighed
      all adipose tissue (range 9.7-25.7 kg), allowing the calculation of percentage
      adiposity as 100 x total adipose mass/body mass (range 17.8-43.9%). Adipose
      tissue volume was determined by hydrostatic weighing of all portions of the
      dissected adipose tissue. For the six cadavers, whole body adipose tissue density
      ranged from 0.925-0.970 g/ml. Based on a three-component model of adipose tissue
      (lipid, water and dry fat-free solids), an expression for lipid fraction, F, was
      derived. After assuming densities for adipose lipid (0.905 g/ml), water at 36
      degrees C (0.997 g/ml) and the dry fat-free component (1.38 g/ml), the equation
      simplified to F = 6.256/D-5.912, where D is adipose tissue density (g/ml). Lipid
      fraction was then calculated for each of the six cadavers: the range (0.54-0.85)
      was in excellent agreement with published data. There was a significant
      correlation (r = 0.95, P < 0.005) between calculated lipid fraction and
      percentage adiposity. The regression equation predicting lipid fraction from
      percentage adiposity was y = 0.327 + 0.0124x. We conclude that the estimated
      fraction of lipid in human adipose tissue shows both a wide range and a strong
      positive linear relationship with overall body fatness.

PMID- 8148929
TI  - Predictors of weight change in a bi-ethnic population. The San Antonio Heart
      Study.
AB  - To study demographic, anthropometric and metabolic determinants of weight change,
      we divided a random sample of 1493 Mexican Americans and non-Hispanic whites into
      two groups: weight gainers and weight losers. This classification was based on
      the weight change during the eight-year follow-up of participants of the San
      Antonio Heart Study, a population-based longitudinal study of diabetes and
      cardiovascular disease. Men gained significantly less weight and lost more weight
      than women. The average gains for weight gainers were 6.1 kg and 6.8 kg for men
      and women respectively; and the average losses for weight losers were 4.4 and 3.4
      kg for men and women respectively. There was no ethnic difference in either
      category of weight change. Weight gainers were significantly younger and leaner
      than weight losers. Fasting insulin was the only independent metabolic predictor
      of weight change and only among the most obese tertile of the population: the
      higher the baseline levels of fasting insulin, the less the likelihood of gaining
      and the greater the likelihood of losing weight. Our results support the
      hypothesis that insulin resistance is part of a negative feedback mechanism that
      attenuates further weight gain among the obese.

PMID- 8148930
TI  - Reduced effectiveness of atrial natriuretic factor in pre-menopausal obese women.
AB  - It is well-known that the prevalence of hypertension progressively increases with
      body weight. Since the major physiological activities of atrial natriuretic
      factor (ANF) are its natriuretic, diuretic and vasodilatory effects, the aim of
      the present study was to investigate the ANF basal plasma levels and platelet
      receptor number in 15 young normotensive obese (O) and 12 age-matched normal
      weight healthy (C) women. ANF effectiveness was also studied in eight of the
      obese and seven of the control women, after an intravenous bolus of the hormone
      (human ANF (99-126): 0.5 mg/kg body weight). Results are expressed as means+s.d.
      Basal ANF plasma levels were similar between obese (18.2 +/- 9.7 pg/ml) and
      control women (12.3 +/- 7.7 pg/ml), whereas obese patients showed an increase
      density of platelet ANF-binding sites (clearance receptors) (C: 28.7 +/- 33.5
      fmol/10(9) cells; O: 39.6 +/- 4.6 fmol/10(9) cells; P < 0.001), without apparent
      differences in receptor affinity (Kd) (C: 6.0 +/- 3.0 pM; O: 7.0 +/- 2.0 pM). The
      biological response to ANF, evaluated by changes of mean blood pressure levels
      (C: 5 +/- 1 mmHg; O: 1 +/- 1 mmHg; P < 0.001) and the percentage increase of
      diuresis (C: 159 +/- 52%; O: 81 +/- 62%; P < 0.01) and natriuresis (C: 205 +/-
      129%; O: 99 +/- 41%; P < 0.05) was significantly reduced in obese patients. The
      percentage increase in sodium excretion was inversely related to the basal
      insulin concentrations in the obese group (r = 0.64, P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8148931
TI  - Comparison of an ephedrine/caffeine combination and dexfenfluramine in the
      treatment of obesity. A double-blind multi-centre trial in general practice.
AB  - In previous separate studies, dexfenfluramine (DF) and ephedrine/caffeine (EC)
      have been shown to promote weight loss in obese patients as compared with
      placebo. In order to compare the efficacy and safety of these two anorectic
      drugs, 103 patients with 20-80% overweight were included in a 15-week double
      blind study in general practice. Patients were randomized to either 15 mg DF
      twice daily (n = 53), or 20 mg/200 mg ephedrine/caffeine three times a day (n =
      50), supplementary to a 5 MJ/day diet. Forty-three patients from the DF group and
      38 from the EC group completed the study. After 15 weeks of treatment, the DF
      group (n = 43) had lost 6.9 +/- 4.3 kg and the EC group (n = 38) had lost 8.3 +/-
      5.2 kg (mean +/- s.d., P = 0.12). In the subgroup of patients with BMI > or = 30
      kg/m2 (n = 59), the mean weight loss was 7.0 +/- 4.2 kg in the DF group (n = 29)
      and 9.0 +/- 5.3 kg in the EC group (n = 30), P < 0.05. Both systolic and
      diastolic blood pressures were reduced similarly during both treatments. Twenty
      three patients in the DF group (43%) and 27 in the EC group (54%) complained of
      side-effects. Central nervous system side-effects, especially agitation, were
      more pronounced in the EC group (P < 0.05), whereas gastro-intestinal symptoms
      were more frequent in the DF group (P < 0.05). The side-effects declined markedly
      during the first month of treatment in both groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8148932
TI  - Fire and ice.

PMID- 8148933
TI  - Immunization coverage in a population-based sample of Maryland children.
AB  - OBJECTIVE: To describe the vaccination coverage of a population-based sample of
      Maryland children. DESIGN: Historical cohort study using stratified cluster
      sampling. Strata were formed from five state regions and public and private
      schools within each region. SETTING: Random sample of elementary schools in
      Maryland. SUBJECTS: Immunization records were obtained for a randomly selected
      cohort of 1938 first-grade children in Maryland. OUTCOME MEASURES: Age of
      completion of recommended childhood vaccines and proportion of vaccines given
      simultaneously. RESULTS: By first grade, 95.2% of the sample of Maryland children
      were documented to have received at least four doses of the diphtheria and
      tetanus toxoids and pertussis (DTP) vaccine, three doses of oral poliovirus (OPV)
      vaccine, and one dose of measles-mumps-rubella (MMR) vaccine. However, only 54.8%
      of children surveyed had achieved this level of immunization by 24 months of age.
      For children whose immunizations were up to date on their first birthday (78.7%
      of children surveyed), vaccine providers failed to administer one dose of DTP,
      OPV, and MMR vaccines to 30% of these children during the second year of life.
      Only 16.2% (n = 313) of children sampled received an MMR vaccination
      simultaneously with any dose of DTP or OPV vaccine. CONCLUSIONS: This study shows
      that while immunization levels are very high at school entry, there are serious
      delays in vaccine administration before school entry. These delays are observed
      regardless of whether children are in public or private schools or attend school
      in an urban, suburban, or rural area. Physicians and health care providers could
      play an important role in age-appropriate vaccination by administering vaccines
      simultaneously.

PMID- 8148934
TI  - Trends in asthma-related admissions among American Indian and Alaskan native
      children from 1979 to 1989. Universal health care in the face of poverty.
AB  - OBJECTIVE: To describe changes in asthma-related hospitalizations in Indian
      Health Service facilities and compare with national trends. DESIGN: Trend
      analysis. PATIENTS AND SETTING: Hospital discharge records of patients aged 17
      years and younger treated by the Indian Health Service between 1979 and 1989.
      MAIN OUTCOME MEASURES: Patients discharged with asthma as the first listed
      diagnosis. RESULTS: The rates of asthma-related hospitalizations increased an
      average of 2.6% (95% confidence interval [CI], 0.1 to 5.2) per year between 1979
      and 1989 among American Indian and Alaskan Native children aged 0 to 17 years.
      The increase was 3.7% among the 0- to 4-year age group (95% CI, 2.0 to 5.5) and
      0.3% (95% CI, 0.26 to 0.3) among the 5- to 17-year age group. Boys tended to have
      a higher rate of increase (4.3% [95% CI, -0.1 to 8.7]) compared with girls (2.6%
      [95% CI, -0.2 to 5.4]). The rates for any hospitalization decreased during this
      period for 0- to 4-year-olds (-7.5% [95% CI, -10.5 to -4.5]). Little change was
      noted in hospitalization rates for lower respiratory tract diseases. Diagnostic
      transfer from bronchitis/bronchiolitis to asthma could not explain the increase.
      Both first admission and readmission for treatment of asthma contributed to the
      increase. Compared with previously published data, 0- to 4-year-old American
      Indian and Alaskan Native children more closely approximate white children than
      black children in both rates of hospitalization (1979-1987) and annual percentage
      increase in hospitalization (1979-1989 for American Indian and Alaskan Native
      children and 1979-1987 for white and black children) for the treatment of asthma.
      CONCLUSIONS: American Indian and Alaskan Native children who are cared for by the
      Indian Health Service have asthma-related hospitalization patterns that are
      similar to those seen in white children despite having socioeconomic
      characteristics more similar to those of black children.

PMID- 8148935
TI  - The termination of a randomized clinical trial for poor Hispanic children.
AB  - OBJECTIVE: To conduct a randomized clinical trial of the Spanish version of an
      educational program designed to be an adjuvant to adequate medical care of
      children with asthma. DESIGN: Randomized, clinical trial. SETTING: Los Angeles
      County, Calif. PARTICIPANTS: One hundred thirty-eight Hispanic children, ages 7
      to 12 years, from disadvantaged families. All had used emergency facilities of
      major local hospitals in the previous year. MEASUREMENT/MAIN RESULTS: As the
      study proceeded, it became apparent that subjects were receiving inadequate
      medical and nursing care and had numerous barriers to applying knowledge and self
      care skills gained from the program. Realizing this, we considered it unethical
      to allow the control children to suffer for the duration of the trial (1 year).
      Therefore, all children received "adequate" care from the research staff, and the
      randomized clinical trial, as originally designed, was ended. The emergency
      department/hospital use by both groups was significantly reduced compared with
      previous experience. CONCLUSION: Those researchers conducting randomized trials
      involving poor children should be aware of the potential ethical problems
      inherent in such ventures.

PMID- 8148936
TI  - Laboratory monitoring of children with precocious puberty.
AB  - It is necessary not only to perform laboratory tests for the correct diagnosis of
      children with precocious puberty, but also to monitor laboratory tests to ensure
      adequacy of therapy. Careful laboratory testing is a requisite in the
      differentiation of central from peripheral precocious puberty. It is also
      required to determine whether the patient who presents with early physical
      changes of pubertal development with peripheral precocious puberty has evidence
      of pubertal hormonal secretion. The most useful single test is gonadotropin
      releasing hormone (gonadorelin) stimulation of luteinizing hormone release. The
      same stimulation test is also indicated to verify the adequacy of suppression of
      gonadotropin secretion among patients with central precocious puberty who are
      being treated with gonadotropin-releasing hormone analogue. It is necessary to
      know which gonadotropin assay is being used and the range of normal levels to
      correctly interpret the tests.

PMID- 8148937
TI  - A gradient relationship between low birth weight and IQ at age 6 years.
AB  - OBJECTIVE: To test for a suspected adverse effect of low birth weight (< or =
      2500 g) on IQ at age 6 years in two socioeconomically disparate populations.
      DESIGN: Nonconcurrent prospective study. SETTING: An urban, predominantly
      disadvantaged population and a suburban middle-class population in southeastern
      Michigan. PARTICIPANTS: Low-birth-weight (N = 473) and normal-birth-weight (N =
      350) subjects, randomly selected from the 1983 through the 1985 newborn lists of
      two major hospitals, one serving an urban and the other a suburban population.
      MAIN OUTCOME MEASURES: The Wechsler Intelligence Scale for Children-Revised to
      measure IQ. RESULTS: The mean full-scale IQ of low-birth-weight children was 4.9
      points lower than that of normal-birth-weight children, controlling for
      population site, maternal IQ, maternal education, and race (95% confidence
      interval [CI], 3.0 to 6.8). There was no evidence of low-birth-weight interaction
      with population site, and the same IQ difference was detected in both
      populations. In the urban population, low birth weight was associated with an
      increased risk for IQ below 85 (odds ratio, 2.2; 95% CI, 1.3 to 3.7). In the
      suburban population, low birth weight was associated with an increased risk for
      IQ below 100 (odds ratio, 2.0; 95% CI, 1.2 to 3.4). A gradient relationship with
      full-scale IQ was observed, with the largest deficit in those born weighing 1500
      g or less, an intermediate deficit in those born weighing 1501 through 2000 g,
      and the least pronounced deficit in those born weighing 2001 through 2500 g.
      CONCLUSIONS: The overall effect of low birth weight represents an increase of
      approximately 10% of low-birth-weight children with an IQ of more than 1 SD below
      the population's mean. Children born weighing 2000 g or less bore the major
      burden of the IQ deficits.

PMID- 8148938
TI  - Birth weight and hospital readmission of infants born prematurely.
AB  - OBJECTIVE: To determine whether the hospital readmission rate of infants born
      prematurely was greatest in those whose birth weight was less than 750 g. DESIGN:
      A prospective cohort study. SETTING: Regional neonatal intensive care unit.
      PATIENTS: Consecutive very-low-birth-weight (< 1500 g) infants admitted to the
      neonatal intensive care unit; infants with congenital abnormalities were
      excluded. Two-year follow-up was completed for 109 (90.8%) of these patients.
      MEASUREMENTS/MAIN RESULTS: Following discharge from the neonatal intensive care
      unit, infants were seen at 6-month intervals at which time a detailed history was
      taken and examinations were performed. Hospital admissions were documented and
      confirmed from the medical records. Infants with birth weights of less than 750 g
      and those of very-low gestational age (< or = 28 weeks) made up the greatest
      number of admissions and had the longest hospital stays. In the first year of
      life, the duration of stay was inversely related to birth weight. CONCLUSION:
      Increased survival of extremely low-birth-weight infants has important
      implications for resource allocation of pediatric beds.

PMID- 8148939
TI  - Inherited antithrombin III deficiency in the neonate.
AB  - OBJECTIVE: To describe two cases of inherited antithrombin III (AT-III)
      deficiency presenting at less than or equal to 28 days of age, and to review
      other neonatal reports. RESEARCH DESIGN: Clinical descriptions of two patients
      and literature review of known references to the neonatal presentation of this
      disorder. SETTING: Academic neonatal intensive care unit. PATIENTS: Case reports-
      two patients with thrombosis and family history of AT-III deficiency. Literature
      review--neonatal patients with thrombosis and diagnosis of AT-III deficiency or
      parental diagnosis of AT-III deficiency or diagnosis of AT-III deficiency alone.
      SELECTION PROCEDURES: Random observation (case reports) and literature search for
      cases of AT-III deficiency diagnosed in the neonatal period or presenting with
      thrombosis and a positive family history of the disorder. INTERVENTIONS: Fresh
      frozen plasma, heparin, and AT-III concentrate were employed in the current case
      reports. The cases from the literature used combinations of the above or no
      intervention. MEASUREMENTS/MAIN RESULTS: Twenty-three cases, including the
      current reports, of suspected or proved AT-III deficiency were found, with at
      least 11 cases of thrombosis and at least 10 deaths. CONCLUSIONS: Significant
      morbidity and mortality from inherited AT-III deficiency can occur in the
      neonatal period, and the incidence of affected neonatal patients is probably
      underestimated. Careful family history, early recognition, diagnosis, and
      specific treatment are important for management of this disorder.

PMID- 8148940
TI  - Age as a risk factor for burn injury requiring hospitalization during early
      childhood.
AB  - OBJECTIVE: To examine the variation by age in the rates and causes of burn injury
      requiring hospitalization during early childhood. DESIGN AND SETTING: Hospital
      discharge data and a burn unit admission log were used to identify all children
      in the Denver (Colo) metropolitan area younger than 5 years who sustained burn
      injuries and were hospitalized in 1989 and 1990. Patients' medical records were
      reviewed. RESULTS: One hundred twenty-two children were identified with burn
      injuries that required hospitalization, an annual incidence of 40.5 per 100,000
      children younger than 5 years. Children aged 6 months through 2 years accounted
      for 88% of all cases and were seven times more likely to be hospitalized for a
      burn injury than were children outside this age range. Scalding and contact with
      hot objects accounted for 64% and 20% of cases, respectively, and occurred
      primarily in the 6-month through 2-year age group. CONCLUSIONS: The findings
      underscore the importance of developmental stage as a determinant of risk and
      type of burn injury. Children aged 6 months through 2 years are at increased risk
      of severe burn injury and should be targeted for prevention efforts.

PMID- 8148941
TI  - Anticardiolipin antibodies in pediatric systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the prevalence and the clinical significance of
      anticardiolipin antibodies (ACLs) in a group of children with systemic lupus
      erythematosus (SLE). DESIGN: Cross-sectional and longitudinal study. SETTING:
      Pediatric Clinic, University of Pavia, Italy. PARTICIPANTS: Thirty children (aged
      4.9 to 16.5 years) with SLE. MEASUREMENTS AND MAIN RESULTS: Twenty-six (87%) of
      the 30 patients were initially positive for either IgG or IgM ACLs; 24 (80%) of
      30 had IgG ACLs, and 15 (50%) of 30 had IgM ACLs. The cross-sectional analysis
      showed a trend for IgG ACLs to be positively associated with autoimmune cytopenia
      and negatively associated with renal disease. The levels of ACLs, particularly of
      the IgG isotype, tended to correlate with SLE activity as expressed by the
      complement fraction C3, the erythrocyte sedimentation rate, or the SLE Activity
      Measure, but not by the SLE Disease Activity Index or the anti-DNA antibodies.
      Serial determinations of ACL levels in 20 patients revealed frequent
      fluctuations. High levels of IgG ACLs (> 50 arbitrary units) were observed in
      nine patients; all nine had active disease and eight had one or more clinical
      features that have been previously associated with antiphospholipid antibodies:
      neuropsychiatric manifestations in six patients, autoimmune cytopenia in two
      patients, and avascular necrosis of bone in one patient. Only one patient
      experienced an overt episode of vascular thrombosis; IgG ACLs were positive at a
      medium level 6 months before the thrombotic event, but their level was unchanged
      when the thrombosis was discovered; the lupus anticoagulant test was positive at
      time of the thrombosis. CONCLUSIONS: Our results show that in pediatric SLE, ACLs
      are frequently found, high levels of IgG ACLs are often associated with central
      nervous system involvement, and ACLs have a low predictive value in the
      development of vascular thrombosis.

PMID- 8148942
TI  - A program to develop residents as teachers.
AB  - Residents are recognized as important and influential teachers of medical
      students. Although they are expected to teach and evaluate students, few
      residents have been taught how, and most would like to receive training to
      develop and improve their skills as teachers. We developed a "Residents as
      Teachers" retreat based on our faculty development program for clinical
      preceptors. We focused on clinical precepting skills, including
      evaluation/feedback, and the ability to prepare and deliver a brief presentation.
      The program increased knowledge and skills and improved attitudes about teaching,
      as reflected in self-reports, observed performance, and medical student ratings.
      The retreat also provided a valuable social experience for residents. The program
      has been considered beneficial by residents, program faculty members, medical
      students, the student clerkship director, and the residents' primary care
      preceptors. The retreats form the centerpiece of our curriculum for residents as
      teachers and have become an annual tradition in the residency program.

PMID- 8148943
TI  - Consanguineous matings in an Israeli-Arab community.
AB  - OBJECTIVE: To determine the frequency of consanguineous marriages and the
      inbreeding coefficient in Israeli Arabs. DESIGN: Cohort survey. SETTING: General
      community in 70 settlements in Israel. PARTICIPANTS: Nine thousand three hundred
      Israeli-Arab students in the second grade were sent questionnaires to be filled
      out by their fathers, with 8521 completed questionnaires returned. INTERVENTIONS:
      None. MEASUREMENTS/MAIN RESULTS: Of the 8521 completed questionnaires, 1156 (14%)
      were from urban areas, 2267 (27%) were from suburban areas, and 5098 (60%) were
      from rural areas. The prevalence of consanguineous matings in the studied group
      was 44.3%, with a mean inbreeding coefficient of .0192. This prevalence is high
      and was highest in the rural areas. Marriages between first cousins occurred more
      often than marriages between other relatives in all locations. CONCLUSION: The
      frequency of consanguineous marriages is quite high among Israeli Arabs,
      approaching 50%.

PMID- 8148944
TI  - Radiological cases of the month. Congenital hiatal hernia.

PMID- 8148945
TI  - Radiological cases of the month. Esophageal coins.

PMID- 8148946
TI  - Picture of the month. Congenital depressed skull fracture.

PMID- 8148947
TI  - Pathological cases of the month. Kikuchi's disease (histiocytic necrotizing
      lymphadenitis).

PMID- 8148948
TI  - Pathological cases of the month. Erythema multiforme (EM).

PMID- 8148949
TI  - The adolescent pelvic examination: an update of a successful program.

PMID- 8148950
TI  - Infant 'abandonment' by drug-using mothers: blaming the victims?

PMID- 8148951
TI  - Chloride deficiency syndrome in older exclusively breast-fed infants.

PMID- 8148952
TI  - Hypothyroidism in patients with Down syndrome.

PMID- 8148953
TI  - Cytomegalovirus and latency: an overview.
AB  - Cytomegalovirus (CMV) is a member of the herpes virus group. Infection results in
      a variety of disorders which depend largely on the immune status of the host. A
      well known property of CMV is that after primary infection the virus persists in
      the body of the host resulting in latency. Severe immunodepression or
      immunodeficiency can cause reactivation of the virus from its latent state,
      leading to endogenous reinfection. In contrast to other herpes viruses, such as
      herpes simplex virus which persists in neurons, and Epstein Barr virus which
      persists in B lymphocytes, little is known about the localization of latent CMV.
      In order to obtain more insight in the organ or cell type serving as a reservoir
      for latent CMV, it is important to know more about the course of natural
      infection and the cells and organs involved. When more information is available
      about the localization of latent virus, studies concerning the physical state of
      viral DNA or the extent of viral transcription and/or translation will follow in
      the near future. In this review some properties of the epidemiology and
      transmission of human CMV, as well as data about acute infection will be given.
      In addition, some characteristics of the localization of latent CMV and the
      physical state of the virus will be discussed. Where necessary, particularly
      regarding insight into CMV-host interactions, knowledge of animal, particularly
      murine, rat and guinea pig CMV infections, will be discussed.

PMID- 8148954
TI  - Phenotypical and functional analyses of mononuclear cells during rejection of a
      transplanted murine fibrosarcoma.
AB  - Repeated injections of mitomycin C-treated T2 fibrosarcoma cells into tumor
      sensitized mice cause regression of a secondary tumor graft and more than 90% of
      the mice are cured. In the data presented here, an enhancement of the cytolytic
      cell-mediated activities measured in vitro against the specific T2 targets is
      shown in lymph nodes draining the tumor and in the spleen during the process of
      tumor rejection. Histopathologic studies revealed a rapid and marked accumulation
      of mononuclear cells mostly at the periphery of the rejected tumor tissue. A
      significant increase of CD8-positive, asialo GM1-positive and acid phosphatase
      positive cells was observed in the rejected tumors whereas CD4-positive cells
      were similarly detected in both progressing and rejected tumor tissue. As
      macrophages seemed to be the population presenting the most persistent variation
      after immunization, the production of TNF-alpha was studied within the tumor site
      and in the lymphoid tissues during the regression process. Firstly, the presence
      of TNF-alpha within the cytoplasm of most of the adherent cell fractions isolated
      from the spleen and the tumor of immune mice was demonstrated by
      immunocytochemistry. Next, TNF-alpha mRNA-containing cells were determined by in
      situ hybridization of frozen tumor sections and identified essentially as tumor
      infiltrating macrophages. Finally, the macrophage populations isolated from
      tumors and from the spleen of immune mice were able to produce in vitro large
      quantities of TNF-alpha without exogenous stimulation. These findings support the
      role of TNF-alpha in the effector mechanisms contributing to the tumor regression
      process.

PMID- 8148955
TI  - Activation and enhanced contact of human T-lymphocytes with autologous red blood
      cells are required for their stable adherence at 37 degrees.
AB  - The adherence of human red blood cells (RBC) to autologous T-cells does not occur
      in the body, and in vitro is elicited at 4 degrees. Autologous E-rosetting at 37
      degrees has not previously been described. In this work, lymphocyte-RBC adherence
      has been studied in mixed leukocyte-RBC cultures and in whole blood from healthy
      donors. Vital, cytochemical and electron microscopic studies have shown that T
      cells may form stable E-rosettes with autologous RBC at 37 degrees. As in the
      previously reported cold-dependent reversible rosetting, stable rosetting is
      mediated by the erythrocyte LFA3 and lymphocyte CD2 molecules. Uniquely, this
      phenomenon requires both T-cell activation and an enhanced contact between the T
      cell and RBC membranes. These requirements were met by exposure of cell cultures
      to: (1) PHAE, the erythroagglutinating component of PHAP, or (2) to either non
      erythroagglutinating mitogens, PHAL, Con A, OKT3 or SEA, or to antigens of typhus
      group rickettsiae or salmonellae, provided that the RBC membrane was desialyted.
      Cultures derived from individuals seropositive to rickettsiae or vaccinated with
      salmonellae demonstrated the adherence phenomenon after antigen exposure when
      neuraminidase was present in the culture medium. The system 2 described here can
      be used as a diagnostic tool for defining activated T-cells and T-cell clones
      with the memory to antigens capable of inducing cell-mediated immunity.

PMID- 8148956
TI  - In situ hybridization of albumin mRNA in normal liver and liver tumors:
      identification of hepatocellular origin.
AB  - In situ hybridization was performed to detect albumin mRNA in normal liver, liver
      cirrhosis, primary liver tumors and secondary liver neoplasms. In areas of normal
      liver, and liver cirrhosis, signals for albumin mRNA were present in hepatocytes,
      whereas no signals were seen in other cells such as endothelial and Kupffer
      cells, bile duct epithelium and smooth muscle cells. In 53 of 56 hepatocellular
      carcinomas signals were present in tumor cells but in eight cholangiocarcinomas
      and 14 metastatic adenocarcinomas from large bowel or pancreas, carcinoma cells
      were negative for albumin mRNA. In three metastatic tumors (from two
      neuroendocrine carcinomas and one gastric leiomyosarcoma), tumor cells contained
      no signals, while the surrounding hepatocytes showed diffuse grains. In 15 of the
      84 specimens examined in situ hybridization was applied to routine formalin-fixed
      and paraffin-embedded blocks and strong signals were obtained for albumin mRNA.
      We conclude that in situ hybridization of human albumin is a valid tool in the
      differential diagnosis of hepatocellular carcinoma from cholangiocarcinomas and
      tumors metastatic to the liver.

PMID- 8148957
TI  - Interleukin 6-producing malignant mesothelioma.
AB  - Systemic amyloidosis of the amyloid A (AA) type, is occasionally associated with
      various neoplasms, but the cause is still unclear. We obtained interleukin 6 (IL
      6)-producing cells designated YO from a primary culture of a malignant peritoneal
      mesothelioma of epithelial type obtained from a 62-year-old woman. Post mortem
      examination revealed that the patient had systemic amyloidosis of the AA type.
      The supernatant media of YO cells, as well as recombinant human IL-6,
      successfully induced nonneoplastic liver cells to produce serum AA (SAA). Our
      data suggest that IL-6 produced by the tumor cells may have played an important
      role in the paraneoplastic syndrome of AA amyloidosis in this patient.

PMID- 8148958
TI  - Sympathetic hyperinnervation protects vascular smooth muscle cells from necrosis
      in stroke-prone spontaneously hypertensive rats.
AB  - Sympathetic nerve fiber distribution and vascular smooth muscle morphology were
      investigated in the ophthalmic artery of stroke-prone spontaneously hypertensive
      rats (SHRSP) and were compared with those of normotensive Wistar Kyoto (WKY) rats
      at the age of 120 days. The distribution of fluorescent noradrenergic (NA) nerve
      fibers was examined by the glyoxylic acid method. The ophthalmic artery was
      divided into two portions according to the size of the outer diameter, that is
      into a proximal portion (above 100 microns) and a distal portion (30-70 microns).
      The distribution densities of noradrenergic nerve fibers were measured by
      quantitative image analysis using the Interactive Bild-Analyse System (IBAS). The
      distribution densities of NA nerve fibers in both portions of the ophthalmic
      artery were significantly higher (p < 0.01) in SHRSP than that in WKY rats. The
      difference in the density of NA fibers of the ophthalmic arteries between SHRSP
      and WKY rats was 1.9 times in the proximal portion and 1.5 times in the distal
      portion. The vascular smooth muscle cells of the ophthalmic arteries in SHRSP
      were observed by scanning electron microscope to examine the trophic effect of NA
      nerve fibers on the vascular smooth muscle cells. The smooth muscle cells of both
      portions of the ophthalmic arteries in SHRSP showed a smooth surface texture and
      no necrosis, and were very similar to those of WKY rats.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8148959
TI  - An immunohistochemical study of human pituicytes demonstrating frequent
      expression of MHC class II antigens and macrophage markers.
AB  - Using a panel of antibodies (Abs) and a lectin, normal human adult pituicytes
      were studied in neurohypophyses obtained from 29 patients at autopsy. The
      pituicytes reacted frequently with Abs against major histocompatibility complex
      (MHC) class II antigens (Ags), macrophage markers (KP.1, PG.M1, LN-5), an anti
      vimentin Ab and a biotinylated lectin Ricinus communis agglutinin (RCA-1). The
      number of pituicytes immunostained for these reagents varied, with the notable
      exception of vimentin. MHC class II Abs (LN-3, CR3.43)-positive pituicytes were
      numerous in approximately half. Microscopically, MHC class II Ag was found in
      pituicytes of various shapes, and were identified in macrophage-typed pituicytes
      by electron microscopic immunohistochemistry. Glial fibrillary acidic protein was
      found in only a small number of pituicytes and was absent in cells labeled with
      MHC class II Abs or macrophage markers. The results indicate that the
      immunophenotype of human pituicytes is distinct from other glial cells of the
      central nervous system, with a considerable number of cells expressing MHC class
      II Ags and macrophage markers.

PMID- 8148960
TI  - Human hepatocyte polyploidization kinetics in the course of life cycle.
AB  - The processes of polyploidization in normal human liver parenchyma from 155
      individuals aged between 1 day and 92 years were investigated by Feulgen-DNA
      cytophotometry. It was shown that polyploid hepatocytes appear in individuals
      from 1 to 5 years old. Up to the age of 50 years the accumulation rate of
      binucleate and polyploid cells is very slow, but subsequently hepatocyte
      polyploidization is intensified, and in patients aged 86-92 years the relative
      number of cells with polyploid nuclei is about 27%. Only a few hepatocytes in the
      normal human liver reach 16C and 8C x 2 ploidy levels for mononucleate and
      binucleate cells respectively. Using a mathematical modeling method, it was shown
      that during postnatal liver growth the polyploidization process in human liver is
      similar to that in the rat, and that polyploid cells are formed mainly from
      binucleate cells. As in rats, prior to an increase in ploidy level, diploid human
      hepatocytes can pass several times through the usual mitotic cycles maintaining
      their initial ploidy level. After birth, only one in ten hepatocytes starting DNA
      synthesis enters the polyploidization process. At maturity about 60% of 2C
      hepatocytes starting DNA synthesis divide by conventional mitosis, the rest
      dividing by acytokinetic mitosis leading to the formation of binucleate cells.
      During ageing the probability of hepatocyte polyploidization increases and in
      this period there are two polyploid or binucleate cells for every diploid
      dividing by conventional mitosis.

PMID- 8148961
TI  - Ultrastructural interaction between multinucleate giant cells and the fungus in
      aspergillomas of human paranasal sinuses.
AB  - The interaction between multinucleate giant cells (MGCs) and the fungus
      Aspergillus flavus as seen by transmission electron microscopy (TEM) is described
      in paranasal granulomas occurring in a Saudi patient dying from chronic
      aspergillosis. Two morphologically different types of MGCs were recognized; these
      were: a) 'Unhealthy looking' type I cells, rich in well organized organelles and
      containing few, partially degenerated and necrotic fungal elements. b) 'Healthy
      looking' type II cells that contained scanty, randomly dispersed cell organelles
      and normal, or partially degenerated fungal hyphae. The fungal elements had very
      thick and multilayered cell walls, and were found either in close contact to the
      host cell cytoplasm, or enclosed within phagosomes. The mechanism of the fungus
      destruction by the host MGCs is described and compared with that previous reports
      of MGCs involved in the elimination of extracellular microorganisms. The
      morphology and the various physiological activities of MGCs seems to depend
      mainly on whether the pathogen is extra- or intracellular. However, this study
      showed that MGCs are the cells best suited for killing pathogenic fungi.

PMID- 8148962
TI  - Effect of reactive oxygen species on lysosomal membrane integrity. A study on a
      lysosomal fraction.
AB  - Using a lysosome-enriched "light mitochondrial" fraction of a rat liver
      homogenate, the effects of the reactive oxygen species hydrogen peroxide,
      superoxide- and hydroxyl radicals were determined. Alterations in the
      intralysosomal pH and the release of a lysosomal marker enzyme, N-acetyl
      glucosaminidase, were used as indicators of changes in the lysosomal membrane
      integrity. Lipid peroxidation of the fraction was assayed by TBARS measurement.
      Neither superoxide radicals, generated by hypoxanthine/xanthine oxidase, nor a
      bolus dose of hydrogen peroxide (0.5-1.5 mM) induced any lysosomal damage. If,
      however, Fe(III)ADP was included in the superoxide radical-generating system,
      lysosomal membrane damage was detected, both as an increase in lysosomal pH and
      as a release of N-acetyl-glucosaminidase, but only after a lag phase of about 7
      min. Lipid peroxidation, on the other hand, proceeded gradually. Lysosomes
      treated with hydrogen peroxide displayed similar dose-dependent alterations,
      albeit only if both Fe(III)ADP and the reducing amino acid cysteine were added.
      In the latter system, however, alterations of the lysosomal membrane stability
      occurred more rapidly, showing a lag phase of only 2 min. Lipid peroxidation,
      which proceeded faster and displayed no lag phase, levelled out within 10 min.
      The results indicate that neither superoxide radicals nor hydrogen peroxide are
      by themselves damaging to lysosomes. Available catalytically active iron in
      Fe(II) form, however, allows reactions yielding powerful oxidative species-
      probably hydroxyl radicals formed via Fenton reactions--to take place inducing
      peroxidation of the lysosomal membranes resulting in dissipation of the proton
      gradient and leakage of their enzyme contents.

PMID- 8148963
TI  - [The effect of hypo- and hypermagnetic fields on the motor activity of the
      ciliary apparatus of the ependymal cells].
AB  - The effect of vertical component of geomagnetic field on ciliate apparatus of
      ependymal cells in newborn rats in culture has been studied. It has been shown
      that hypo- and hypermagnetic fields retard the motor activity of ciliary
      apparatus up to full stoppage with cell swelling.

PMID- 8148964
TI  - [The reproductive function of male rats in the late periods after x-ray
      irradiation].
AB  - Reproductive function in male rats was studied in 1, 3 and 6 months after X-ray
      irradiation of doses of 2 and 3 Gy. It has been established that long-term
      effects of irradiation at a dose of 3 Gy are manifested through decrease in
      spermatozoa content in the epididymis and reduction of nucleic acid and protein
      content in the testes. Fertility of male rats under study significantly lowered
      shortly after irradiation and full recovery of fecundating ability was observed 6
      months later. The effect of irradiation with a dose of 2 Gy was less pronounced.

PMID- 8148965
TI  - [The role of the hemopoiesis-inducing microenvironment in the postradiation
      regeneration of hemopoiesis].
AB  - The dynamic of granulocytic macrophages and erythroid precursors content in bone
      marrow of CBA mice, irradiated by 2.0 Gy and the level of colony-stimulating and
      erythropoietic activities in supernatant of bone marrow myelocariocytes and blood
      serum were studied. The process of haemopoiesis regeneration was accompanied by
      increasing of the values of these indexes in bone marrow and peripheral blood.
      The treatment of bone marrow cells by monoclonal antibodies to Thy 1.2 antigens
      resulted in decreasing of myeloid precursors and diminishing of colony
      stimulating activity of bone marrow cells supernatant.

PMID- 8148966
TI  - [Microvascular hemostasis in the phase of postradiation recovery].
AB  - Laser-induced thrombosis was used for studying of thrombogenic properties and
      thromboresistance of microvessels after total gamma irradiation with a dose of 2
      Gy. The increased time of primary haemostasis was stated during postirradiation
      period. The area of thrombus section was reduced both in the arterioles and the
      venules after 1 month. But the normalization of this parameter is more intense in
      the venules.

PMID- 8148967
TI  - [The pharmacological mechanisms of the radioprotective effect under whole-body
      conditions and the prospects of the search for radioprotectors].
AB  - On the basis of the current views of the pharmacological agents action and the
      analysis of the structural and functional mechanisms of the radioprotection
      realization a unitary hypothesis of the radioprotective effect development has
      been formulated. Three stages of its development in animals and humans have been
      distinguished. The proposed hypothesis allows to substantiate a strategy of the
      search for new antiradiation drugs.

PMID- 8148968
TI  - [The essential questions of constructing a theory of radioprotective action on
      the body].
AB  - The most disputable points of an universal hypothesis concerning radioprotective
      action are discussed. The attention is focused on the question whether it is
      necessary to differ the ways of radioresistance development in organism and the
      sites of its realization to the radioprotective effect.

PMID- 8148969
TI  - [The radiotherapeutic effect of the CM-5 fraction of turtle spleen extract].
AB  - CM-5 fraction of tortoise spleen extract injected after irradiation in dose
      CD50/30 (540 R) raises a survival of mice to 73.4%. The number of endocolonies of
      spleen increases to 4.0 in experiment against 0.3 in control and the average life
      of experimental animals increases to 12.7 days against 8.8 in control. In vitro
      it has been found a considerable increase of RNA-synthetic activity of bone
      marrow cells stimulated by CM-5 fraction in post-irradiation period. The dose
      alteration factor for CM-5 fraction is 1.46 according to CD50/30 standard at
      survival test.

PMID- 8148970
TI  - [A decrease in the damaging action of gamma irradiation on human lymphocytes by
      postradiation treatment with the preparation MDI].
AB  - The effect of MDI, the agent of plant origin, on the cell cycle and the number of
      micronuclei in human lymphocytes after gamma-irradiation has been studied. It has
      been found that the treatment of lymphocytes with MDI stimulates DNA synthesis
      and reduces the delay of irradiated cells in (G2 + M) phase. Moreover post
      irradiation cell treatment with MDI reduces the number of damaged cells.

PMID- 8148971
TI  - [The modifying influence of thermal injury on the postradiation changes in the
      biochemical and functional activities of peritoneal macrophages].
AB  - The effect of thermal injury on radiation-induced (3-7 Gy) changes in
      quantitative and qualitative composition, biochemical and functional activity of
      the peritoneal macrophages was studied. The reduce of peritoneal cells total
      number and alterations of their qualitative composition were conditioned by
      radiation component of combined radiation end thermal injury (CRTJ). The enzymes'
      activity and the protein content in macrophages were the most enhanced 7-9 days
      after CRTJ as compared with the effect of radiation per se. The early and the
      most pronounced luminol- and lucigenin-enhanced chemiluminescence increase in
      zymosan stimulated macrophages was conditioned by thermal component. The
      mechanisms of increase in the macrophages functional activity induced by
      radiation end CRTJ are discussed.

PMID- 8148972
TI  - [The cytogenetic effect in the seeds from natural Crespis tectorum populations in
      long-term storage subjected to chronic irradiation as a result of the radioactive
      pollution in a 30-kilometer area of the accident at the Chernobyl Atomic Electric
      Power Station].
AB  - Seeds of the 1st and 3d Crepis tectorum natural populations subjected to chronic
      irradiation during 4 months in 1986 within 30 km zone of Chernobyl accident were
      stored for 5 years in laboratory. For this period germination capacity of 1st
      population seeds decreased but the seeds retained a germination capacity up to
      1992 were characterized by the increased germination rate. The germination
      capacity and the germination rate of 3d population seeds did not change. The
      frequency of metaphases with chromosome aberrations in the first mitotic cycle of
      root tip meristematic cells of seedlings increased after 5 year storage: from 9.1
      +/- 0.44 to 13.0 +/- 0.57% in 1st population and from 2.6 +/- 0.27 to 3.8 +/-
      0.38% in 3d population.

PMID- 8148973
TI  - [The characteristics of unscheduled DNA synthesis and of the changes in the
      structural parameters of human lymphocyte nuclei after the action of x-ray
      radiation in low doses and in combination with UV irradiation].
AB  - Effects of X-ray low doses (0.5-25 cGy) with following UV light (254 nm, 20 J/m2)
      on human peripheral blood lymphocytes were studied. Reparation response
      registered by unscheduled DNA synthesis (UDS) activity was demonstrated to be the
      most intensive after action of X-rays in dose ranges 2-3 cGy and 15-20 cGy, and
      least intensive after 10 cGy. In those cells where UV light was followed by X
      rays, dose ranges 2-3 cGy and 15-20 cGy cause essential decrease of UDS as
      compared with UV-light action only. The most intensive UDS was in those UV
      irradiated lymphocytes which where previously exposed to 10 cGy of X-rays. At the
      same time 10 cGy cause minimal reparation response without UV light. Possible
      mechanisms of discovered phenomena are discussed. In particular, reaction on 2-3
      cGy might be a reorganization of genome for adaptive response or an evolution
      reserve cells response. From 10 cGy the reason of reaction might be a reparation,
      induced by radiation.

PMID- 8148974
TI  - [Antibodies to the thyroid microsomal antigen in children and adolescents
      subjected to radiation exposure as a result of the accident at the Chernobyl
      Atomic Electric Power Station].
AB  - For evaluation of the possibility of the appearance of autoimmune thyroiditis in
      children and juveniles lived in the areas of Kaluga Province [correction of
      region] suffered from the Chernobyl accident the content of antibodies to human
      thyroid microsomal antigen was investigated. Percentage of positive sera varied
      from 4.8% to 1.2% during 6 years. There is significant difference in the
      frequency of the antibody appearance between persons suffered from radioactive
      iodine and unsuffered ones. Correlation between levels of antimicrosomal
      antibodies and radiation dose obtained from incorporated radioactive iodine was
      not estimated.

PMID- 8148975
TI  - [Prostaglandins--their role in the mechanisms of the development of the primary
      reaction to radiation syndrome].
AB  - In experiments with dogs and rats it has been shown that early after high doses
      of irradiation, the content of prostaglandins in the blood plasma increases,
      whereas in the intestinal tissues it decreases. The inhibitors of prostaglandins
      synthesis indomethacin and voltaren hinder the development of early digestive
      disturbances, normalize the intestine absorptive and propulsive functions and
      make post-irradiation hypokinesia less pronounced. Possible mechanisms of the
      prostaglandins involvement in the genesis of prodromal radiation syndrome are
      discussed.

PMID- 8148976
TI  - [The effect of the blood plasma from irradiated animals on the Ca2(+)- and Mg2(+)
      ATPase activity in thymocyte plasma membranes].
AB  - Rats were irradiated at doses 1.5, 4.0, 7.0 and 10 Gy. After 1, 8, 15, 22 and 30
      days the effect of blood plasma on activity of Ca(2+)-ATPase and Mg(2+)-ATPase in
      plasma membrane of thymocytes was investigated. It was found that the raise of
      irradiation dose leads to increasing of blood plasma effect on membrane-bound
      enzymes.

PMID- 8148977
TI  - [The effect of ionizing radiation on the Mg2(+)-binding proteins of thymocyte
      plasma membranes].
AB  - The effect of ionizing radiation at doses 10, 10(2), 10(3) and 10(4) Gy on Mg(2+)
      binding plasma membrane proteins in thymocytes was studied. Marked changes in the
      Mg(2+)-binding protein structure-dynamic organization at doses above 10(3) Gy
      were found.

PMID- 8148978
TI  - [The effect of the repeated irradiation of rats on the Ca2(+)- and Mg2(+)-ATPase
      activity of thymocyte plasma membranes].
AB  - Rats were daily irradiated at doses 0.5 Gy in period of two weeks. The activity
      of Ca(2+)-ATPase, Mg(2+)-ATPase and the extent of lipid peroxidation in thymus
      were determined. The peculiarity of changing of enzymes activity demonstrates the
      dependence of Mg(2+)-ATPase on lipid peroxidation.

PMID- 8148979
TI  - [Blood trace elements as an indicator of the degree of severity in radiation
      lesions].
AB  - Changes of selenium, chromium, antimony, silver, cobalt, rubidium, zinc, iron and
      bromine concentration in whole blood of Wistar rats were examined in early period
      after gamma irradiation by 3, 7.5 and 10 Gy. Level of these trace elements was
      measured by instrumental neutron activation and X-ray fluorescence analysis.
      Diagnostic and prognostic significance of some trace elements were established.

PMID- 8148980
TI  - [The functional dynamics of the system of immunity in rats during adaptation to
      single and fractionated exposures to low doses of external gamma irradiation].
AB  - The content of serum corticosterone so as immunological and nonspecific
      reactivity in rats exposed to single or fractionated gamma-radiation (0.35 Gy)
      were studied during 1 month. It has been revealed that corticosterone level,
      dynamics of absolute amount of leucocytes, lymphocytes, Rc-receptor-bearing cells
      in blood, relative content of FcR(+)-cells in bone marrow, spleen and peripheral
      lymph nodes of irradiated animals depend on the scheme of irradiation. Single
      irradiation didn't significantly influence natural and antibody-dependent killer
      cells activity and basal chemiluminescence level of polymorphonuclear cells,
      while the fractionated irradiation in equal dose induced considerable
      fluctuations of these parameters. The direction and intensity of the disturbances
      depend on the time after irradiation.

PMID- 8148981
TI  - [Functionally active T-cells and T-lymphocyte precursors in the thymus of newborn
      mice irradiated in the intrauterine period of development].
AB  - Mice were irradiated in dose of 2 Gy in 14 or 17 days of gestation. Irradiation
      retarded the increase of cell number in developing thymuses but in the day of
      birth the number of thymocytes was normalized. In normal development SC-1+ cells
      (T cell precursors) disappeared from the thymus immediately before the birth.
      After the irradiation they persisted in the newborn thymus. Mitogenic responses
      of newborn thymocytes on the action of thymic peptides and T cell mitogens were
      decreased after the fetal irradiation (adult irradiation enhances mitogenic
      response of thymocytes). The helper activity of thymocytes in humoral immunity
      was decreased after the fetal irradiation in more degree and helper activity in
      splenic colony-formation--in less degree than after the adult irradiation. The
      consequences of the irradiation in 14 and 17 days of gestation were similar.

PMID- 8148982
TI  - [The significance of the radioactive isotope potassium-40 for the normal
      development of the animal organism].
AB  - 21-day-old rats subjected to nourishing by KCl (20-30 mg per day) without
      radioactive isotope 40K. Besides the decrease of 40K content in animal tissue (30
      50%) a reducing of body weight was obtained. In the second set of experiments in
      the lead (9 cm thick) chamber with low (20 times) background radiation the
      trustworthy decrease of young mouse development was observed under the
      simultaneous reducing other components of background radiation (radon, products
      of its disintegration, gamma, beta radiation, cosmic radiation). Possible
      mechanisms of necessity of 40K natural concentration for the normal development
      of the animal organism are discussed.

PMID- 8148983
TI  - [The probable causes of thyroid diseases in the victims of the Chernobyl
      accident].
AB  - Ideas about the thyroid gland diseases development in people suffering from the
      Chernobyl accident explaining the absence of straight dose dependence of
      pathologies raise from the irradiation were elaborated. It is supposed that the
      probable reason for a number of these pathologies can be the inadequate and
      inopportune preventive iodine administration. It is known that significant amount
      of iodine being incorporated in children or persons with compromised thyroid
      gland could lead to a number of pathological changes, primarily to autoimmune
      thyroiditis which is a reason of other consequent pathologies of this organ. The
      principal mechanism of the process can be presented as following: iodine
      transformation (oxidation) in the thyroid gland accompanies with the generation
      of considerable quantities of various radicals imitating the radiation damage.
      This hypothesis allows to consider the children suffered from the Chernobyl
      accident with autoimmune thyroiditis as belonging to the group of risk as the
      literary data testify that the presence of autoimmune thyroiditis rises 75 time
      the risk of malignant lympho-proliferated diseases appearance. A simple
      immunological method of autoimmune thyroiditis diagnostics was developed which
      informativity is comparable with the method of ultrasound diagnostics. Serial
      production (the antibodies to microsomal fraction of thyroid gland) was
      organized. This method can be used in screening investigations.

PMID- 8148984
TI  - [A realistic approach to the modelling of nonuniform whole-body radiation
      exposures in a radiobiology experiment].
AB  - The equidosimetric principle for modelling of general nonuniform radiation
      effects has been formulated. The method for realistic modelling of the effects by
      dynamic control of radiation exposure of two basic critical systems (active bone
      marrow and intestine) has been developed.

PMID- 8148985
TI  - [The early reaction of the neuroendocrine system to irradiation at high doses].
AB  - It has been found that in 2 hours after the total gamma irradiation of rats at
      doses of 20 and 100 Gy the ACTH and glucagon levels in plasma increased by 5-6
      and 10-12 times correspondingly. No significant changes in levels of plasma
      insulin and glucose have been revealed.

PMID- 8148986
TI  - [The kinetics of polykaryon formation in a HeLa cell culture after irradiation at
      doses of 5 and 10 Gy].
AB  - Monolayer culture of HeLa tumor cells irradiated at 5 Gy and 10 Gy doses was
      followed up in kinetics for 14 days. It was shown that starting with day 3 the
      cell monolayer is modified in such a way that some cells occur in 2- to 8-cell
      accumulations. The rate of formation of such groups and the number of cells in
      them were dose-related. The labeling index in these formations was several times
      higher than that in the irradiated population on the whole. The analysis of the
      grade of DNA synthesis synchronization in these accumulations showed that
      complete cell fusion and polykaryon formation after irradiation at the dose of 10
      Gy occurred on day 4 whereas after 5 Gy, only on day 7. In both cases the status
      of complete fusion was 3 days in duration.

PMID- 8148987
TI  - Determination of drugs by direct injection of plasma into a biocompatible
      extraction column based on a protein-entrapped hydrophobic phase.
AB  - Drugs were determined by direct injection of plasma samples into a biocompatible
      extraction column. The column is based on particles with a biocompatible external
      surface and a hydrophobic internal surface. The pores of the particles are small
      enough to exclude the protein molecules; the drug molecules can penetrate the
      porous particle and are retained on the hydrophobic internal surface.
      Biocompatibility of the particles was obtained by reaction of the external
      surface with the human plasma protein alpha1-acid glycoprotein. The surface
      within the pores of the particles contains hydrophobic C8 or C18 groups. The
      biocompatible extraction column was used in a fully automated system for the
      determination of ibuprofen, naproxen, propranolol, carbamazepine and phenytoin in
      plasma. No pressure increase was observed during the analysis of several hundred
      plasma samples. Plasma concentrations of propranolol in the range 4.5-125 ng/ml
      were determined with a precision (R.S.D.) of 0.75-1.8%. Linear calibration graphs
      were observed for the five drugs, and correlation coefficients of 1.0000 were
      obtained for four of the five model compounds.

PMID- 8148988
TI  - Perfusible and non-perfusible supports with monoclonal antibodies for bioaffinity
      chromatography of Escherichia coli penicillin amidase within its pH stability
      range.
AB  - Several monoclonal antibodies (mABs) have been prepared and immobilized for the
      biospecific isolation of penicillin amidase (PA) from Escherichia coli (EC
      3.5.1.11), an enzyme without S-S bridges and a pH stability range of 4-9. During
      the immobilization the fluorescence emission maxima of the mABs were found to
      change from 336 nm to ca. 350 nm. Only one of these mABs was found to be suitable
      for preparative bioaffinity chromatography of PA within the pH stability range.
      This mAB was immobilized on different spherical supports (Eupergit C 250 L and
      Sepharose) and one perfusible support (Knauer Quick Disc) and used for analytical
      and preparative bioaffinity chromatography. Under isocratic conditions the plate
      height for the perfusible biospecific adsorbent was found to be an order of
      magnitude lower than for the other supports. The different forms of this
      proteolytically processed bacterial enzyme could not be separated, however, by
      the biospecific adsorbents. At the mAB density used in the adsorbents (10-30
      microM), less than 30% of the theoretical binding capacity of the immobilized
      mABs could be used to adsorb the enzyme.

PMID- 8148989
TI  - Enzyme-based biosensor as a selective detection unit in column liquid
      chromatography.
AB  - A reagentless enzyme electrode based on co-immobilized alcohol oxidase and
      horseradish peroxidase was used as the working electrode in an amperometric flow
      through cell connected to a column liquid chromatographic (CLC) system for the
      selective detection of methanol and ethanol. The enzymes were covalently
      immobilized in carbon paste (graphite-phenylmethylsilicone oil) in the presence
      of polyethylenimine. Electrodes prepared from the enzyme-modified carbon paste
      were optimized with respect to their sensitivity and selectivity. Different
      membranes were cast or electropolymerized directly on the surface of the
      electrode to increase the long-term stability of the biosensor. The compatibility
      with the reversed-phase chromatographic system was established. A PLRP-S polymer
      based separation column was used with phosphate buffer as the mobile phase. The
      selectivity of the enzyme electrode was also determined by injecting some easily
      oxidizable and possibly interfering species normally present in biological
      samples. The enzyme electrode was also used in an on-line system, consisting of a
      microdialysis probe as the sampling unit, the CLC system and the biosensor
      detection device, for the selective following of the ethanol produced when a
      paper pulp industrial waste water was fermented with Saccharomyces cerevisiae.

PMID- 8148990
TI  - Synergies between micropreparative high-performance liquid chromatography and an
      instrumental optical biosensor.
AB  - The recent development of an automated surface plasmon resonance technology for
      the measurement of biomolecular interactions (Pharmacia BIAcore) has provided new
      opportunities for the detection and analysis of protein-protein interactions. In
      the BIAcore, detection is based on changes in surface plasmon resonance which are
      monitored optically. Changes in surface plasmon resonance correspond to changes
      in surface concentration of macromolecules and can be monitored in real time. We
      have found that the detection sensitivity obtainable with this technology (ng/ml
      concentrations of specific ligands are readily detectable for many applications)
      is complementary "in a bidirectional manner" to micropreparative HPLC. Thus
      micropreparative HPLC may be used to purify and characterise reagents for the
      biosensor, whilst the biosensor may be used to define chromatographic parameters
      such as elution conditions for affinity chromatography or serve as an affinity
      detector for fractions obtained during chromatographic purification. Examples of
      such applications, including the potential of the biosensor to search for and
      monitor the purification of unknown ligands for which the target molecule has
      been identified, are shown. In particular, the use of the biosensor to monitor
      the purification of soluble epidermal growth factor receptor from A431 cell
      conditioned media is demonstrated.

PMID- 8148991
TI  - Determination of traces of pyrethrins and piperonyl butoxide in biological
      material by high-performance liquid chromatography.
AB  - A liquid chromatographic method for the determination of pyrethrins and of the
      synergist piperonyl butoxide in human plasma after C18 solid-phase extraction is
      described. UV detection was found to be sensitive enough to determine
      concentrations far below the limit of toxicity. With respect to future
      investigations concerning studies in biological materials, a column-switching
      system for sample preparation was developed and compared with solid-phase
      extraction. Both methods show comparable limits of detection, but the column
      switching technique has the advantage of fully automating the system.

PMID- 8148992
TI  - High-performance liquid chromatographic determination of FCE 24928, a new
      aromatase inhibitor, in human plasma.
AB  - A sensitive and selective high-performance liquid chromatographic method for the
      determination of FCE 24928 (4-amino-androsta-1,4,6-triene-3,17-dione) in human
      plasma is reported. The drug was extracted from buffered (pH = 8) plasma samples
      with methylene chloride-isooctane, then analysed by reversed-phase liquid
      chromatography. Quantitation was achieved by ultraviolet detection of the eluate
      at 238 nm. Blank plasma samples from humans, dog and rat assayed as described
      showed no significant peak at the retention time of the compound of interest. The
      suitability of the method for in vivo samples was tested by measuring the plasma
      levels of FCE 24928 in rats that received oral doses of the test compound.

PMID- 8148993
TI  - Simultaneous determination of L-693,612, a topical carbonic anhydrase inhibitor,
      and two potential metabolites in human whole blood by ion-pair high-performance
      liquid chromatography.
AB  - A method for the simultaneous determination of a topical carbonic anhydrase
      inhibitor, L-693,612, and two of its potential metabolites in human whole blood
      is described. The analytes are isolated from the matrix via liquid-liquid
      extraction with a mixture of toluene, ethyl acetate and isopropanol (49:50:1,
      v/v/v). The analytes are then back extracted into dilute phosphoric acid prior to
      injection into the HPLC system. A cyano column (Zorbax SB-CN, 150 x 4.6 mm) with
      a mobile phase of phosphoric acid(0.085%)-acetonitrile (73.5:26.5) containing 10
      mM sodium decane sulfonate and adjusted to pH 3 is used for the analysis.
      Detection is based on UV absorbance at 252 nm. The assay was found to be linear
      in the concentration range of 5-500 ng/ml for each analyte when 1-ml aliquots of
      whole blood were extracted.

PMID- 8148994
TI  - Automated assay for GV104326, a novel tribactam antibiotic, in human plasma by
      high-performance liquid chromatography and solid-phase extraction.
AB  - A highly automated, rapid, robust and specific plasma assay for GV104326, a novel
      tribactam antibiotic, has been developed to monitor human volunteer trials. The
      method involves automated solid-phase extraction with a strong anion-exchange
      phase and HPLC on a reversed-phase column with ultraviolet detection. The
      calibration range for the assay is 0.05-2 micrograms/ml. The assay is linear over
      this range and is specific with respect to endogenous interference and likely
      metabolites of GV104326. Both intra- and inter-assay variability were < 8% and
      intra- and inter-day bias < 10%.

PMID- 8148995
TI  - Rapid, high-resolution high-performance liquid chromatographic analysis of
      antibiotics.
AB  - A HPLC column devised for high separation speed combined with highly practical
      operating features has been found useful for separating antibiotics. Important
      characteristics involved compromises in packing particle size, column
      configuration and support-stationary phase combinations. We determined that these
      columns are useful for rapid, high-resolution separations with unmodified state
      of-the-art HPLC equipment without the extra-column band-broadening effects
      typical of so-called "fast" HPLC columns. The proposed columns feature efficient
      sterically-protected monofunctional silane stationary phases that provide good
      separation reproducibility and high column stability. The combination of these
      unique bonded silanes and a highly purified, less-acidic silica support give
      superior peak shapes for antibiotic compounds. The proposed column configuration
      can halve separation times and double peak heights without loss in resolution,
      compared to widely used analytical columns. Increased mobile phase flow-rates
      permit even faster separations of antibiotics with only modest loss in resolution
      and peak heights for trace analyses in biological systems.

PMID- 8148996
TI  - Sensitive procedure for the determination of reboxetine enantiomers in human
      plasma by reversed-phase high-performance liquid chromatography with fluorimetric
      detection after chiral derivatization with (+)-1-(9-fluorenyl)ethyl
      chloroformate.
AB  - A sensitive and selective high-performance liquid chromatographic method for the
      determination of reboxetine enantiomers in human plasma was developed. Although
      two chiral centres are present in reboxetine, its stereospecific synthesis leads
      to two rather than four possible enantiomers. After extraction from plasma and
      reaction with (+)-1-(9-fluorenyl)ethyl chloroformate, reboxetine enantiomers were
      separated as diastereoisomeric derivatives by reversed-phase high-performance
      liquid chromatography (HPLC) and determined by fluorimetric detection. The HPLC
      analysis time was about 90 min. The linearity, precision, accuracy and limit of
      quantification of the method were evaluated. No interference from blank plasma
      sample was observed. The suitability of the method for in vivo samples was
      assessed by the analysis of plasma samples obtained from a healthy male volunteer
      who had received a single oral dose of 4 mg of reboxetine in tablet form.

PMID- 8148997
TI  - Prolegomena to any future code of ethics for bioethicists.

PMID- 8148998
TI  - Ethics consultation: the least dangerous profession?

PMID- 8148999
TI  - Some suggestions for holding bioethics committees and consultants accountable.

PMID- 8149000
TI  - Invoking the law in ethics consultation.

PMID- 8149001
TI  - The ethics consultant and ethics committees, and their acronyms: IRBs, HECs, RM,
      QA, UM, PROs, IPCs, and HREAPs.

PMID- 8149002
TI  - The ethical role of the consultant.

PMID- 8149003
TI  - A description of humanist scholars functioning as ethicists in the clinical
      setting.

PMID- 8149004
TI  - Measuring hospital ethics committee success.

PMID- 8149005
TI  - Does depression invalidate competence? Consultants' ethical, psychiatric, and
      legal considerations.

PMID- 8149006
TI  - CQ sources.

PMID- 8149007
TI  - Assessing bioethics today.

PMID- 8149008
TI  - A matter of conscience: legal protection for the rights of conscience of
      healthcare providers.

PMID- 8149009
TI  - An inquiry into ethics committees' understanding: how does one educate the
      educators?

PMID- 8149010
TI  - 1991 national survey of carcinoma of the breast by the Commission on Cancer.
AB  - A nationwide survey of patterns of care for carcinoma of the breast was conducted
      by the Commission on Cancer of the American College of Surgeons. Information
      regarding patient history, diagnostic tests, treatment, survival and disease
      status was obtained for 17,295 patients treated during 1983 and 24,356 patients
      treated during 1990. The results indicate that patients diagnosed in recent years
      (1990) are being treated at an earlier stage of the disease compared with the
      1983 survey and the findings of earlier years, probably because of the use of
      mammography. Surgical treatment for conservation of the breast is being used more
      frequently, but modified radical mastectomy remains the most commonly used
      surgical treatment.

PMID- 8149011
TI  - A prospective comparison of the status of the deep venous system after treatment
      with intracaval interruption versus anticoagulation.
AB  - The safety and efficacy of caval interruption has been well demonstrated.
      Likewise, comparisons of caval interruption and anticoagulation have shown
      similar rates of mean and long term clinical outcome. One concern that continues
      to be voiced is whether or not anticoagulation enhances venous recovery and
      function. The present study compares outcome by impedance plethysmography, Duplex
      scanning and clinical sequelae at six months after the acute illness and
      treatment with either caval interruption or anticoagulation. The results show no
      significant differences between the two treatment groups.

PMID- 8149012
TI  - Metastases from carcinoma of the colon and rectum detected in small lymph nodes
      by the clearing method.
AB  - A study of regional lymph node metastases was performed using the clearing method
      in 322 patients with carcinoma of the colon and rectum (140 with carcinoma of the
      colon and 182 with carcinoma of the rectum) who had undergone surgical resection.
      The mean number of nodes examined per patient was 76.4 and the metastatic rate
      (patients with metastases divided by the total of patients) was 61.4 percent,
      with a metastatic incidence (nodes with metastases divided by the total of
      examined nodes) of 6.4 percent for carcinoma of the colon using the clearing
      method. For carcinoma of the rectum, the mean number of nodes examined was 73.7
      with a metastatic rate of 57.1 percent and a metastatic incidence of 7.1 percent.
      In contrast, node analysis by the conventional manual method resulted in a mean
      of 18.1 nodes being examined, with a metastatic rate and incidence of 42.1 and
      12.8 percent, respectively, for carcinoma of the colon. Manual examination of
      lymph nodes in carcinoma of the rectum resulted in a mean of 21.2 nodes being
      examined, with a metastatic rate and incidence of 50.0 and 16.8 percent,
      respectively. Compared with the manual method, the clearing method provided a
      greater number of nodes, a higher metastatic rate and a lower metastatic
      incidence. These differences may be explained by the detection of metastatic
      regional nodes smaller than 4 millimeters in maximum diameter by the clearing
      method. By TNM classification there were more pN3 than pN2 lesions. The five year
      survival rate after curative resection was 78.5 percent for pN1 lesions, 45.7
      percent for pN2 lesions and 45.4 percent for pN3 lesions for carcinoma of the
      colon and 72.7 percent for pN1 lesions, 75.0 percent for pN2 and 53.9 percent for
      pN3 lesions for carcinoma of the rectum. There was no significant survival
      difference between the patients with pN1, pN2 and pN3 carcinomas. The presence of
      regional nodes metastases should be examined in detail. Therapies and prognosis
      of carcinoma of the colon and rectum should be discussed based on accurate
      staging.

PMID- 8149013
TI  - Bile duct injury during laparoscopic and conventional cholecystectomy.
AB  - It has been suggested that the risk of injury to the bile duct is higher after
      laparoscopic cholecystectomy than after conventional cholecystectomy. The results
      of previous studies on laparoscopic cholecystectomy showed no difference but they
      were limited (positive) selections from highly specialized centers. Thus, a
      questionnaire was sent to all surgical departments in The Netherlands to analyze
      the number of repair procedures for bile duct injury, the techniques and
      complications of this treatment and the number of cholecystectomies performed
      during 1991 to determine the "actual" risk of bile duct injury. The response was
      88.4 percent (122 of 138 centers). A total of 11,712 cholecystectomies were
      performed, of which 2,932 were laparoscopic and 8,780 were conventional. Thirty
      two bile duct injuries resulted from laparoscopic cholecystectomy (1.09 percent)
      and 45 resulted from conventional cholecystectomy (0.51 percent) (p < 0.001).
      Thirty-six injuries (46.7 percent) were detected during the procedure or within
      24 hours and 41 (53.2 percent) after a mean period of ten days. The bile duct
      lesion consisted of transection in 35 patients (45.5 percent), a stenosis or
      clips in 17 patients (22.1 percent) and a lesion with bile leakage in 25 patients
      (32.5 percent). The repair procedure included primary closure or end to end
      anastomosis in 33 patients (42.8 percent) and hepatojejunostomy in 31 patients
      (40.2 percent). Hepatojejunostomy was performed upon 17 percent of the injuries
      detected early and in 61 percent of the injuries detected after a delay.
      Complications were found in 31.1 percent and the mortality rate was 7.8 percent.
      In summary, the risk of bile duct injury after laparoscopic cholecystectomy was
      significantly (p < 0.001) higher than after conventional cholecystectomy, which
      was probably related to the relative inexperience (all units from one country).
      The risk of bile duct injury after conventional cholecystectomy was slightly
      higher than that found in literature, which probably reflects the fact that we
      studied the number of "repair procedures" instead of registration of
      complications (injury). Repair procedures for lesion detected after a delay are
      more complicated (hepatojejunostomy) than for the injury detected early.

PMID- 8149014
TI  - The pediatric diaphragm in acute gastric volvulus.
AB  - Acute gastric volvulus occurred in nine infants and one older child during the
      past 19 years; all patients had an associated left diaphragmatic anomaly. There
      were seven examples of eventration of the diaphragm, two of giant hiatal hernia
      and one Bochdalek hernia. Nine of the ten patients presented with vomiting and
      one with acute respiratory distress. The gastric volvulus was mesenteroaxial in
      eight patients and organoaxial in two. Operative treatment consisted of repair of
      the diaphragmatic anomaly and gastric fixation in eight patients. Gastric
      fixation alone was performed in one patient. A single patient died preoperatively
      and had gastric necrosis at postmortem examination. Of the nine patients treated
      operatively, all remain alive and well without recurrence. Acute gastric volvulus
      should be considered in any infant presenting with unexplained vomiting in
      association with a left diaphragm anomaly, and once diagnosed, immediate
      operation is mandatory.

PMID- 8149015
TI  - The diagnostic value of magnetic resonance imaging for the detection of tumor
      recurrence in patients with carcinoma of the ovaries.
AB  - Disease status during follow-up evaluation of patients with carcinoma of the
      ovaries is the main criterion for the selection of appropriate management. A
      cohort analysis was performed to investigate if magnetic resonance imaging (MRI)
      could improve noninvasive assessment of disease status in patients with carcinoma
      of the ovaries during follow-up examination. Twenty-four women with carcinoma of
      the ovaries after primary surgical treatment with subsequent platinum containing
      chemotherapy were entered into the study. MRI was performed in addition to
      sonography and computed tomography (CT). Patients without evidence of disease
      underwent restaging laparotomy. Sensitivity of sonography, CT and MRI was 50, 63
      and 75 percent, respectively. Combination of CT and MRI revealed a 75 percent
      sensitivity rate. Specificity for sonography, CT and MRI was 100, 94 and 94
      percent, respectively, and for the combination of CT and MRI, 88 percent.
      Positive and negative predictive value and accuracy of these methods were 100, 80
      and 83 percent for sonography; 83, 83 and 83 percent for CT; 86, 88 and 88
      percent for MRI, and 75, 88 and 83 percent for the combination of CT and MRI. In
      one instance of false-negative sonographic and CT results, MRI detected
      recurrence located in postoperative scar tissue. In one instance, MRI did not add
      essential information to the other imaging methods. Therefore, MRI as a time- and
      cost-intensive procedure should be reserved for instances in which there are
      doubtful findings arising with other diagnostic tools, rather than as an
      indispensable routine procedure in the follow-up evaluation of patients with
      carcinoma of the ovaries.

PMID- 8149016
TI  - Defecation mechanisms in conscious dogs after total colectomy with ileorectal
      anastomosis.
AB  - To clarify defection mechanisms in those with total colectomy, we performed
      comparative studies of intestinal motility in two groups of straight and J-pouch
      ileorectal anastomosis. In the straight group, 98 percent of the interdigestive
      migrating contractions (IMC) reached the anastomosis and 48 percent of the
      defecations were affected by the contractions. In the J-pouch group, 16 percent
      of the contractions reached the anastomosis and only 8 percent of the defecations
      were related to the contractions. We conclude that transmission of IMC to the
      rectum is related to the frequency of defecation after total colectomy and that
      the disappearance of IMC in the J-pouch anastomosis reduced the frequency of
      defecations in those instances.

PMID- 8149017
TI  - Clinical significance of duodenal diverticula.
AB  - Duodenal diverticula are found in up to 22 percent of the population. According
      to the literature, less than 10 percent of duodenal diverticula will cause
      symptoms, and about 1 percent will require definite treatment. There is no
      indication for treatment of asymptomatic patients with duodenal diverticula. A
      trial of conservative treatment is justified if the symptomatic patient is in
      stable condition. If symptoms persist or serious complications are present and
      other pathology of the abdomen that might be responsible is ruled out, definitive
      treatment is necessary. For intraluminal duodenal diverticula an elective
      endoscopic approach is possible. Our approach for extraluminal duodenal
      diverticula is discussed herein. The clinical presentations of 50 patients from
      1986 to 1992 are summarized. In a surprisingly high proportion (12 percent), the
      symptoms could be clearly related to the duodenal diverticula. Eight percent were
      treated surgically, and postoperative mortality rates zero. In the literature,
      postoperative mortality rates even for elective surgery are 8 to 12 percent and
      reach 20 percent for emergency operations.

PMID- 8149018
TI  - Cryptic presentations of germ cell tumors.
AB  - The records of 636 patients who were treated for carcinoma of the testis were
      reviewed. Of these patients, 61 (9.6 percent) presented with extratesticular
      complaints. In order of decreasing frequency, the complaints were pain
      (abdominal, back or groin), gynecomastia or mastodynia, pulmonary complaints,
      enlarged lymph nodes or a nontesticular mass, swelling of the lower extremity or
      neurologic changes. A substantial number of these patients were initially
      misdiagnosed and underwent a surgical procedure. Of importance, most of these
      patients had either abnormal testicular examination results, elevated markers or
      a history of cryptorchidism. The data suggest that patients with germ cell
      tumors, even when presenting with cryptic complaints, can readily be diagnosed if
      a high level of suspicion is maintained, a careful testicular examination is
      performed and tumor markers obtained. This frequently makes a diagnostic
      abdominal exploration or other surgical interventions unnecessary.

PMID- 8149019
TI  - Hypercoagulable states as an evolving risk for spontaneous venous and arterial
      thrombosis.
AB  - This study of 49 patients with spontaneous venous and arterial thrombosis
      identified 27 with hypercoagulable states: 13 had only venous thrombosis (VT),
      six had episodes of VT followed by arterial thrombosis (AT) and eight had AT
      only. All 27 patients were less than 42 years of age; 22 had specific natural
      anticoagulant or fibrinolytic deficiencies: antithrombin III (nine patients),
      protein C (eight patients), protein S (three patients), heparin cofactor II (two
      patients), tissue plasminogen activator release (one patient) and mixed
      antithrombin III and protein S (one patient). The remaining five patients had
      recurrent thrombotic events associated with resistance to heparin
      anticoagulation, but no established laboratory diagnosis. Clotting complications
      included recurrent VT, pulmonary embolism, multiple failed arterial procedures
      and lower extremity amputation. The remaining 22 patients (mean age of 53 years,
      range of 46 to 63 years), 12 with VT and ten with AT, did not have laboratory
      evidence of hypercoagulability and none had recurrent vascular occlusions. All
      these patients were successfully treated by conventional therapy without any
      additional thrombotic events during the follow-up period. Young adults with
      spontaneous thrombotic events should be screened for possible hypercoagulable
      states. Additionally, these young patients need further evaluation and treatment
      of cardiovascular risk factors. Those with premature atherosclerosis have an
      especially poor prognosis despite surgical intervention and anticoagulant
      therapy.

PMID- 8149020
TI  - Long-term survival after curative resection for carcinoma of the rectum.
AB  - The clinical outcome of 453 patients with histologically confirmed adenocarcinoma
      surveyed from 1980 to 1992 was evaluated. Special consideration was given to the
      prognostic significance of local recurrence and distant metastases as the
      significant contributors to postoperative morbidity and mortality. Of 453
      patients, 371 were treated by a curative surgical approach. The remaining 82
      patients, with extended disease, received palliative treatment. Among those
      undergoing surgical treatment, the local recurrence rate was 11.3 percent; the
      incidence of distant metastases was 16.2 percent, and 2.7 percent of the patients
      exhibited combined lesions. The five-year survival rate depended on the extent of
      the primary lesion and lymph node status--it was highest for patients with stage
      I adenocarcinoma (80 percent), a rate significantly better (p < 0.01) than
      patients with stage II disease (40 percent), who fared better (p < 0.02) than
      patients with stage III disease (30 percent) (Union Internatinale Contre le
      Cancer [International Union Against Cancer] classification). Sixty percent of the
      patients with local recurrence and almost 70 percent with distant spread showed
      proof of failure within two years. Of 42 patients with local failure, 12
      underwent reoperation without leaving residual tumor (RO-treatment) but exhibited
      no improvement in five-year survival compared with those with no second surgical
      approach. The operative techniques were abdominoperineal resection (36.9
      percent), low anterior resection (58.2 percent) and transanal resection (4.9
      percent). They were without significant influence on long term results. Critical
      analysis of the data emphasizes the urgency of adjuvant treatment for patients
      with poor long term prognosis, as given for stages IIB and III.

PMID- 8149021
TI  - Infected retroperitoneal fat necrosis associated with acute pancreatitis.
AB  - Treatment of necrosis associated with acute pancreatitis is controversial. Forty
      consecutive patients (63.4 +/- 1.4 years of age) with necrotic retroperitoneal
      fat associated with nonalcoholic pancreatitis were treated by debridement and
      closed drainage. None of the patients had overt pancreatic necrosis. Eight
      percent of the patients were operated upon 48.4 +/- 2.9 days (late referrals) and
      20 percent on 4.3 +/- 0.6 days after the onset of pancreatitis. The main
      indication for operation was clinical deterioration. All patients had bacterial
      infection of the necrosis and none had a preoperative invasive procedure. Twenty
      five percent of the patients had colonic necrosis at initial operation; this did
      not progress thereafter. No patient had histologically identifiable pancreas,
      which remained grossly intact at the conclusion of operation. Morbidity included
      postoperative "septic shock" in 97.5 percent of the patients, renal failure in
      40.0 percent and enterocutaneous fistula in 47.5 percent. Reoperation for a
      persistent septic focus was required for 25 percent of the patients. The
      mortality rate was only 2.5 percent. No patient operated upon early had colonic
      necrosis or postoperative worsening of renal function or a fistula or required
      reoperation. The outcome suggests that most patients with infected
      retroperitoneal fat necrosis do not require pancreatic resection. Open drainage
      or use of continuous lavage, or both, are not necessary to achieve a low
      mortality rate. Retroperitoneal necrosis can harbor infection much earlier than
      commonly believed. While mortality has not been clearly shown to be related to
      early or late debridement, early operation upon patients with infected necrosis
      may decrease the morbidity rate.

PMID- 8149022
TI  - Outcome of thirty patients who underwent repair of posthysterectomy prolapse of
      the vaginal vault with abdominal sacral colpopexy.
AB  - Thirty women experiencing posthysterectomy prolapse of the vaginal vault were
      treated with abdominal sacral colpopexy between 1984 and 1991. Lyodura
      (lyophilized cerebral dura mater allograft transplant) was used as the suspensory
      material in 81 percent and Gore-Tex (reinforced polytetrafluoroethylene) in 16
      percent of the operations. There were no perioperative or postoperative
      complications. At the follow-up examination (mean, three years), good vaginal
      vault support was observed in 85 percent of the patients. Significant cystocele
      were seen in 18 percent, and vault prolapse, enterocele, rectocele and chronic
      perineal laceration each in 15 percent of the patients. At follow-up study, 22
      percent of the patients experienced dyspareunia and 41 percent had decreased
      sexual interest and coital events. Development of stress urinary incontinence in
      18 percent of patients was noted. Concomitant Burch colposuspension will cure and
      prevent stress incontinence and anterior vaginal relaxation. Abdominal sacral
      colpopexy appears to be a safe and effective method in the treatment of
      posthysterectomy prolapse of the vaginal vault. In our experience, it seems that
      coexistent cystocele and rectocele should be corrected in the connection with
      sacral colpopexy.

PMID- 8149023
TI  - Extended left hepatectomy with vascular exclusion.
AB  - Extended left hepatectomy represents the most extensive and difficult type of
      hepatic resection. The risk of hemorrhage during transection of the hepatic
      parenchyma and subsequently the risk of biliary complications may be minimized
      with use of hepatic vascular exclusion.

PMID- 8149024
TI  - Portal vein graft in living related hepatic transplantation.
AB  - In living related hepatic transplantation, sclerotic small portal vein and
      thrombosis can impede standard end to end anastomosis of the graft portal vein
      and the recipient portal vein. We have described herein the successful use of the
      donor ovarian vein as the portal vein graft. It offers a safe and simple modality
      that can avoid unnecessary wound to the living donor.

PMID- 8149025
TI  - Surgical trial for carcinoma of the rectum using a tissue expander in association
      with pelvic partition to prevent dysfunction of the bladder.

PMID- 8149026
TI  - Simple technique for assuring completeness of a pyloromyotomy.
AB  - A technique for assuring completeness of a pyloromyotomy is presented. I think
      this simple maneuver adds a sense of security to the operation and can be
      accomplished relatively quickly and with almost no added expense. I recommend its
      consideration to others.

PMID- 8149027
TI  - An efficient system for controlled distal colorectal irrigation.
AB  - We have found this setup to be most useful. For those surgeons who incorporate
      rectal irrigation as part of their treatment plan for patients with rectal
      injuries, we would recommend trial of this simple yet effective technique. The
      more senior anesthesia and nursing staff who have suffered through the vagaries
      of widespread fecal contamination from the beginning to the end of the operation
      rapidly become advocates of this procedure.

PMID- 8149028
TI  - Laparoscopic wedge biopsy of the liver.
AB  - We have created a technique of laparoscopic wedge biopsy of the liver that uses
      the Endo-GIA instrument. Two staple lines are placed at right angles on the edge
      of the liver to release a wedge of hepatic parenchyma. We have used this
      technique as part of a laparoscopic staging procedure for Hodgkin's lymphoma and
      found it to be simple and rapidly performed.

PMID- 8149029
TI  - Pulmonary failure and the production of leukotrienes.
AB  - The activation of neutrophils and elaboration of leukotrienes has a role in the
      pathophysiologic factors of many of the disease states seen by surgeons and
      nonsurgical counterparts. Although direct evidence of cause and effect is
      lacking, there is a growing array of literature proving the importance of
      neutrophils and LTB4 in the pathophysiologic factors of ARDS and MOF after
      significant illness or injury. Experimental and clinical data using alteration of
      arachidonic acid metabolism through drugs or diet should begin to accumulate to
      regulate the detrimental inflammatory response seen after severe illness or
      injury.

PMID- 8149030
TI  - Single-dose cefuroxime versus multiple-dose cefazolin as prophylactic therapy for
      high-risk cholecystectomy.
AB  - The ideal regimen for the prevention of postoperative infections occurring after
      elective cholecystectomy has been widely debated. This double-blind, randomized
      study was conducted to compare the effectiveness and safety of cefuroxime with
      that of cefazolin in 295 patients undergoing elective cholecystectomy who were
      considered to be at high risk for postoperative infection. Patients were randomly
      assigned to receive either a single 1.5 gram dose of cefuroxime plus three doses
      of placebo, or four 1 gram doses of cefazolin. Each regimen was begun 30 to 60
      minutes preoperatively and repeated every six hours for three doses
      postoperatively. Patients were evaluated during the hospitalization period and
      again at 30 days. All postoperative infections, including remote infections, were
      included in the definition of failure. Bacteriologic success rates were 95.5
      percent in the cefuroxime group and 98.2 percent in the cefazolin group (p >
      0.05). Corresponding clinical success rates were 91.4 and 94.9 percent (p >
      0.05), respectively. There was no association between intraoperative bile
      cultures and the risk of failure or the type of microorganism isolated from
      postoperative infections. Both regimens were well-tolerated. In view of the
      additional costs and time associated with preparation and administration of
      multiple doses, a single preoperative 1.5 gram dose of cefuroxime may be a cost
      effective alternative to four 1 gram doses of cefazolin in patients undergoing
      elective cholecystectomy who are at high risk for postoperative infection.

PMID- 8149031
TI  - Endoscopic vesical neck and uterovaginal suspension for cystocele prolapse
      repair.
AB  - The therapeutic surgical approach to cystourethrocele and pelvic organ prolapse
      with or without urinary incontinence usually involves hysterectomy and anterior
      colporrhaphy. This is associated with a high degree of failure and may cause the
      appearance of de novo urinary incontinence because of functional disturbances of
      the lower urinary tract. We report a new combined needle suspension of bladder
      neck and uterine isthmus to correct uterovaginal prolapse and urinary
      incontinence without the need for hysterectomy. This endoscopic procedure is
      minimally invasive, safe, effective and simple. The operative approach is
      flexible, well tolerated and could be adapted to an outpatient setting. It is
      designed to restore the functional pelvic anatomy without extensive operative
      dissection and anterior colporrhaphy.

PMID- 8149032
TI  - Glucose infusion instead of preoperative fasting reduces postoperative insulin
      resistance.
AB  - In severe catabolic states, such as burn injury, sepsis and accidental injury, a
      state of marked insulin resistance is encountered. Insulin resistance is also
      present after elective surgical treatment, more pronounced with increasingly
      greater magnitude of operation performed. Results of recent animal experiments
      have shown that even short periods of food deprivation, reducing carbohydrate
      reserves, alter responses to stress. This notion resulted in our questioning the
      rationale of carbohydrate depletion associated with overnight preoperative
      fasting. Twelve patients undergoing elective open cholecystectomy were randomly
      given no infusion (control group) or 5 milligrams per kilogram per minute of
      glucose infusion (glucose group) during preoperative overnight fasting. Insulin
      sensitivity (M value, milligram per kilogram per minute) was determined using the
      hyperinsulinemic normoglycemic clamp (plasma insulin level, 65 microunits per
      milliliter and blood glucose level, 4.5 millimoles per liter) before and the
      first postoperative day. Preoperative insulin sensitivity was similar in the two
      groups. Postoperatively, M values decreased by 55 +/- 3 percent (control group)
      and by 32 +/- 4 percent (glucose group) (p < 0.01). Plasma levels of insulin, c
      peptide, glucagon, growth hormone, catecholamines and cortisol in connection with
      clamps were similar in both groups preoperatively and postoperatively. The
      present results indicate that active preoperative carbohydrate preservation may
      improve postoperative metabolism because postoperative occurrence of insulin
      resistance was reduced with preoperative glucose infusion.

PMID- 8149033
TI  - Orthotopic hepatic transplantation in patients with type I diabetes mellitus.
AB  - Six transplantations of the liver were performed over a period of six years in
      five adult patients with Type I diabetes mellitus (DM). The diabetic group
      included two males and three females with a mean age of 36 years and a mean
      duration of DM of 20 years. Primary diseases of the liver included two instances
      of primary biliary cirrhosis, two instances of sclerosing cholangitis and one
      instance of autoimmune chronic hepatitis. Three patients also received a
      simultaneous whole organ pancreatic transplant. All patients were managed with
      cyclosporine and prednisone immunosuppression with selective OKT3 induction.
      Patient and hepatic allograft survival rates were 80 and 67 percent,
      respectively, after a mean follow-up period of 4.7 years. One of the three
      pancreatic grafts was successful and resulted in euglycemia for two years. Three
      patients have subsequently undergone successful renal transplantation at one, two
      and one-half, and six and one-half years after hepatic transplantation. Although
      transplantation of the liver can be performed safely in carefully selected
      patients with Type I DM, these patients are still at risk for the development of
      progressive nephropathy. Renal transplantation is an acceptable therapeutic
      alternative when this occurs.

PMID- 8149034
TI  - Pack and close approach to persistent postcardiopulmonary bypass bleeding.
AB  - Persistent intraoperative hemorrhage after cardiopulmonary bypass was managed in
      three patients by packing the suspected bleeding sites with surgical sponges,
      leaving the packs in place and closing all layers of the sternal wound. The
      maneuver reduced the rate of bleeding to acceptable levels. The day after the
      primary operation the wounds were reopened and the surgical sponges were removed.
      Bleeding had ceased and the operative field remained dry in all three patients.
      Definitive closure of the sternotomy incisions was then performed. The method is
      proposed as a simpler alternative to the commonly used approach of leaving the
      mediastinum open for days and closing the wound after the bleeding stopped.

PMID- 8149035
TI  - Interleukin-2 and interleukin-6 in relation to burn wound size in the acute phase
      of thermal injury.
AB  - Thermal injury induces significant physiologic responses of acute inflammation,
      acute phase reaction and cell repair and growth, mediated by interleukins,
      cytokines and growth factors. To determine the relative role of interleukin-2 (IL
      2) and interleukin-6 (IL-6) in the acute phase of thermal injury, 60 patients (47
      men and 13 women, with average age of 37 years [1.5 to 70.0 years]) were analyzed
      within the first 36 hours and at five to seven days postoperatively. The patient
      population was categorized by percent burn (2 or 3, or both, degrees): less than
      20 percent, n = 22; 20 to 40 percent, n = 18, and greater than 40 percent, n =
      20. The average percent burn was 32 percent (range 4 to 95 percent). The
      mechanism of injury was by flame (25 instances), explosion and flame (19
      instances), scald (12 instances), electric (three instances) or chemical (one
      instance). Twelve patients had an associated inhalation injury; 14 patients had
      sepsis syndrome. The overall mortality rate was 13 percent. Within 36 hours of
      onset of injury, IL-6 and IL-2 levels increased in proportion to the severity of
      the burn wound size. IL-2 levels were significantly elevated in the 20 to 40
      percent burn group as compared with the greater than 40 percent group and
      patients in a control group (p < 0.0001). IL-6 levels increased with burn wound
      size and were significant only in the greater than 40 percent group (p < 0.0007).
      Any physiologic modulation of the thermal injury by biologic modifiers must be
      adapted to the extent of burn wound size and phase of injury: acute, recovery or
      reparative for optimal benefit and results.

PMID- 8149036
TI  - Recent advances in the diagnosis and surgical treatment of patients with
      carcinoma of the esophagus.
AB  - Five hundred and eighty-five patients with carcinoma of the thoracic esophagus
      underwent resection of the esophagus in the surgical department in which we work
      since 1965. The postoperative 30 day mortality rate was 11.9 percent during the
      early period, from 1965 to 1974, whereas it has decreased to 1.3 percent in the
      period since 1985. The most common cause of mortality was pulmonary complications
      (45.8 percent). The five year survival rate of patients who underwent a curative
      resection between 1975 and 1984 was only 29.1 percent, whereas it has remarkably
      increased to 49.9 percent since 1985, at which time cervical thoracic and
      abdominal lymph node dissection began to be regularly performed. There were three
      patients with intraepithelial carcinoma and 17 with mucosal carcinoma,
      respectively; none of these patients died within five years postoperatively.
      However, the five year survival rate of 73 patients with submucosal carcinoma of
      the esophagus was only 52.6 percent. Thus, it is clear that the prognosis
      substantially worsens when carcinomatous invasion reaches the submucosal layer.
      From the results of this study, it can be concluded that a combination of early
      detection and resection of the esophagus with three field lymph node dissection
      offers the best chance for long term survival in patients with carcinoma of the
      esophagus.

PMID- 8149037
TI  - The role of transplantation in small hepatocellular carcinoma complicating
      cirrhosis of the liver.
AB  - Of 176 hepatic transplants performed from 1986 to December 1992, 27 patients had
      small hepatocellular carcinoma (< or = 5 centimeters) complicating cirrhosis of
      the liver. All patients were asymptomatic for the hepatic malignancy and the
      diagnosis was established in each instance preoperatively by means of serial
      sonographic scans and alpha-fetoprotein levels. Cirrhosis was classified as
      Child's A in eight instances, as Child's B in 16 and Child C's in three. The
      cause was alcoholic in three patients, posthepatitic in 21 patients (eight
      hepatitis B virus [HBV] positive and 13 hepatitis C virus [HCV] positive) and
      undetermined in three. The in-hospital mortality rate was 11 percent (three of
      27). Additionally, five patients died at different intervals after
      transplantation: only two died of neoplastic recurrence at 12 and 32 months,
      respectively (7.4 percent rate). Actuarial survival rates were 82 percent at one
      year and 71 percent at three years, with a mean follow-up period of 32 months
      (range six to 78 months). Morbidity related to the procedure was a relevant
      problem: 21 percent of the patients had prompt resumption of normal life while 37
      percent required repeated hospitalization and 42 percent required strict control
      on an outpatient basis. The most frequent problem was HBV or HCV reinfection of
      the grafted liver, which occurred in 42 percent. Based on this experience,
      transplantation of the liver has shown an excellent oncologic accuracy for small
      hepatocellular carcinoma in cirrhosis of the liver, thus representing the most
      rational surgical procedure for patients with Child's B and Child's C cirrhosis
      classification. The relevant mortality and morbidity rates, strictly related to
      this procedure, suggest other options as more appropriate in those with Child A
      cirrhosis at this time.

PMID- 8149038
TI  - Chronic and recurrent appendicitis are uncommon entities often misdiagnosed.
AB  - Those having chronic and recurrent appendicitis represent a small portion of
      patients with disorders of the appendix. We present a series of nine patients who
      underwent appendectomy for chronic or recurrent appendicitis at The Johns Hopkins
      Hospital, Baltimore, Maryland, between July 1984 and October 1992. There were
      seven women and two men (median age of 30 years, range of 15 to 63 years). All
      patients presented with pain in the right lower quadrant or lower abdomen of
      three or more weeks duration (mean of 16.0 +/- 8.4 months, range of three weeks
      to seven years), had no alternative diagnosis to account for the symptoms, had
      pathologic evidence of chronic inflammation or fibrosis of the appendix and had
      complete relief of the symptoms after appendectomy. Although the patients
      presented herein had clinical and pathologic evidence for recurrent or chronic
      appendicitis, careful review of the course of each patient before surgical
      referral revealed at least one episode of acute pain in the abdomen consistent
      with acute appendicitis managed by nonoperative means. This suggests that, while
      recurrent acute appendicitis and chronic appendicitis do occur, they can be
      avoided by the accurate diagnosis and operative management of acute appendicitis.
      We conclude that acute appendicitis can resolve spontaneously and recur
      repeatedly in the same individual; in the evaluation of a patient with abdominal
      pain, a history of prior similar episodes of pain should never dissuade one from
      considering the diagnosis of acute appendicitis, and recurrent acute appendicitis
      and chronic appendicitis should be considered in the differential diagnosis of
      recurrent pain in the lower abdomen.

PMID- 8149039
TI  - Occurrence and prognosis of contralateral carcinoma of the breast.
AB  - Of the 4,554 patients who registered at The University of Texas M. D. Anderson
      Cancer Center, Houston, Texas from 1965 to 1988 with a diagnosis of carcinoma of
      the breast and who underwent surgical treatment of at least one carcinoma of the
      breast at this institution, 142 had either a history of a prior carcinoma of the
      breast (metachronous; n = 55) or a contralateral carcinoma of the breast detected
      within four months of registration (synchronous; n = 87). We retrospectively
      studied the records of these 142 patients and found that the occurrence of
      bilateral carcinoma of the breast was low (3.1 percent), the frequency of
      metachronous carcinoma of the breast remained relatively constant over time, the
      nodal status of the second carcinoma of the breast correlated with the method of
      discovery rather than the stage of the first carcinoma of the breast and survival
      rates from the second carcinoma of the breast were similar for metachronous and
      synchronous disease. These data support the role of vigilant surveillance of the
      contralateral breast with screening at the time of initial diagnosis and during
      follow-up evaluation. Because the likelihood of detecting a second carcinoma of
      the breast at an early stage is high, with subsequent good survival rates, the
      use of prophylactic mastectomy should be very selective and based on the
      emotional needs of the patient.

PMID- 8149040
TI  - Extracorporeal circulation as a blood conservation technique for extensive pelvic
      operations.
AB  - Difficult pelvic operations for malignancy or complex benign conditions can be
      associated with extensive blood loss. Religious beliefs that preclude transfusion
      and the known risks of homologous blood have prompted investigators to seek
      alternatives to transfusion. We used the Haemonetics-V50 Cell Separator
      (Haemonetics Corporation) to provide for extracorporeal circulation of the
      patient's own blood with associated normovolemic hemodilution as a means of
      conserving blood during operations. This technique was used in eight patients
      undergoing extensive pelvic operations. The procedure was accepted by Jehovah's
      Witnesses and was well tolerated by all patients. Estimated blood loss ranged
      from 75 to 2,000 milliliters. One instance of mild intraoperative disseminated
      intravascular coagulation was encountered. Two patients were given homologous
      transfusions. While clinical judgment is necessary to determine the safety of
      complicated operations, this technique is useful in expanding surgical options
      for some patients who object to blood transfusion.

PMID- 8149041
TI  - Gasless laparoscopy using a planar lifting technique.
AB  - In clinical use, the mechanical lifting technique has demonstrated the ability to
      displace the abdominal wall and create a useful cavity for visualization and
      surgical manipulation. By forming a planar ceiling, as opposed to the domed
      ceiling of conventional pneumoperitoneum, the abdominal organs are brought into
      closer proximity of the surgeon. Instrument length may be shortened, imparting
      greater surgical control. Without the necessity for gas sealing, entry portals
      are simplified. Conventional instruments (right angle clamps) may be introduced
      through the fan retractor insertion sites or by way of separate stab incisions.
      The planar lifting technique has the potential for simplifying laparoscopy and
      restoring instrument control to the operating surgeon.

PMID- 8149042
TI  - A new improved technique for placement of a pursestring suture on the edge of the
      distal part of the rectal stump using a skin stapler for low anterior resection.
AB  - Instead of a linear stapler or manual pursestring suture onto the lower part of
      the rectum, we placed a No. 2-0 Prolene suture on the edge of the rectal stump,
      using 12 to 16 clips and a disposable skin stapler. This technique is
      satisfactory for very low anterior resection.

PMID- 8149043
TI  - A modified technique for bedside placement of nasoduodenal feeding tubes.
AB  - A technique for bedside placement of NDT that was used in our ICU and allowed a
      significant percentage of feeding tubes to be placed in the duodenum without
      moving the patient from the ICU setting is reported. We believe that this
      modification for feeding tube placement is effective and safe and represents an
      improvement of the previous method.

PMID- 8149044
TI  - Galen--a father of medicine.

PMID- 8149045
TI  - The management of penetrating trauma to the urinary tract.
AB  - Penetrating trauma to the urinary tract is best dealt with early in the overall
      management of the trauma patient. As there are usually other more obvious
      associated injuries, involvement of the urinary tract may be overlooked. Delayed
      management may be of severe consequence to the patient, causing delayed bleeding,
      retroperitoneal abscess and nephrectomy. Patients suspected for urinary trauma
      are those with flank or back wounds, retroperitoneal hematoma, pelvic trauma or
      those presenting with hematuria. The modern approach to trauma emphasizes the
      staging of injury prior to definite management. Appropriate roentgenographic
      studies of the urinary tract should be included in the initial evaluation of the
      patient with trauma. Renal injuries are staged according to severity and method
      of infliction. Stab wounds or low velocity GSW and those of minor or moderate
      degree may be managed conservatively with an acceptably good outcome. High
      velocity GSW usually cause extensive damage and surgical exploration is
      warranted. Ureteric injuries are rare, but prone to be missed at initial
      diagnosis. Emergency roentgenologic studies may be insufficient and must be
      augmented by thorough examination at the initial laparotomy. Hematuria
      accompanies nearly all instances of bladder trauma. The mandatory investigation
      is retrograde cystography. The standard approach to penetrating bladder trauma is
      surgical.

PMID- 8149046
TI  - Wound healing and wound management: focus on debridement. An interdisciplinary
      round table, September 18, 1992, Jackson Hole, WY.
AB  - A multidisciplinary panel of experts convened to discuss the basic concepts of
      prevention and treatment of pressure ulcers. Special emphasis was placed on four
      types of debridement: mechanical, surgical, autolystic, and enzymatic.
      Debridement of burns was also discussed. Team management by informed
      practitioners is vital to successful wound care and all treatments should be
      based on a holistic appraisal of patients and their individualized plans of care.

PMID- 8149047
TI  - Surgical correction of pressure ulcers in an urban center: is it efficacious?
AB  - Recurrence following surgical correction of pressure ulcers remains one of the
      more formidable complications of their treatment. To assess the effect of
      surgical therapy on recurrence, thirty patients were evaluated between 1985 and
      1990 at The Johns Hopkins Hospital. These data were compared to a prior study
      conducted from our institution between 1977 and 1980. Follow-up in this current
      study ranged from 1-108 months. Of the 22 paraplegic patients, pressure ulcers
      recurred at the same site of surgical correction in 82 percent (n = 18), or at a
      different site in 64 percent (n = 14), at an average of 18.2 and 20.2 months
      respectively. No recurrence was noted in the eight non-paraplegic patients. In an
      urban center, surgically corrected pressure ulcers have a high recurrence.
      Physician and patient must be willing to accept a high recurrence rate prior to
      attempted surgical closure.

PMID- 8149048
TI  - Effects of different turn intervals on skin of healthy older adults.
AB  - A comparison of the effects of one-, one and a half-, and two-hour turning
      intervals on changes in the skin surface temperature, interface pressure, and
      color was conducted on 16 older, healthy adults. Both trochanters and the sacrum
      were the sites used for measurement. Findings indicated that the greatest
      increase in skin surface temperature occurred at the end of the two-hour turning
      interval and in the trochanteric positions. No significant differences in
      interface pressure were found with respect to the length of the turning interval
      or body position. A descriptive summary of changes in skin color is also
      presented.

PMID- 8149050
TI  - Classification of ulcers.

PMID- 8149049
TI  - Skin vascular reaction to standard patient positioning on a hospital mattress.
AB  - The effects of duration and posture on reactive hyperemia in the skin overlying
      the greater trochanter of the femur was determined in normal subjects using
      thermography. Multivariate analysis revealed that in the six subjects studied,
      post-lying blood flow within the skin superficial to bony prominences was
      significantly increased over that of the preexperimental and passively-warmed
      controls. These analyses also showed that both maximal interface pressures and
      vascular reactions were experienced in the side-lying position when the legs were
      extended, and significantly reduced when the legs were flexed. While there was
      good correlation between magnitudes of interface pressures measured and vascular
      responses within each individual, there was no such direct correlation between
      individuals. The individual with the highest interface pressures did not have the
      most intense reactive hyperemic reactions, and the individual with the least
      interface pressures did not have the least intense reactive hyperemic reactions.
      Intrinsic features of each individual's vascular response to the normal
      mechanical forces experienced during lying appear to be a sensitive measure of
      the individual's susceptibility to develop pressure ulcers.

PMID- 8149051
TI  - "Turbo charging" the vertical rectus abdominis myocutaneous (turbo-VRAM) flap for
      reconstruction of extensive chest wall defects.
AB  - We report our experience using "turbo charging" of the vertical rectus abdominis
      myocutaneous (turbo-VRAM) flap in 7 patients with extensive chest wall defects.
      The turbo-VRAM flap provides augmented blood supply with microvascular
      anastomosis between the inferior epigastric system and available vessels of the
      axillary, brachial or cervical vascular system. All patients in this study had
      uncomplicated recovery. In 3 patients, the skin paddle of the flap, which was
      designed as a fish shape, was effectively used to cover a wide defect. One
      patient required resection of some lower costal cartilages located near the
      superior epigastric vascular system in order to extend the rotation distance of
      the flap. These technical options have made the turbo-VRAM flap more versatile.
      The turbo-VRAM flap allows successful coverage of extensive chest wall defects,
      including defects of the axilla, upper arm, shoulder, or neck.

PMID- 8149052
TI  - The use of scapular skin island flaps in the treatment of axillary postburn scar
      contractures.
AB  - The scapular island flap easily covers the anterior and posterior aspects of the
      axilla, providing a smooth skin surface with good underlying subcutaneous fatty
      tissue. Its elastic properties are well adapted to the dynamic requirements of
      the shoulder joint. Performed in 20 patients for treatment of axillary postburn
      contractures, this flap led to a convincing improvement of the shoulder range of
      motion and satisfying aesthetic results.

PMID- 8149053
TI  - A two-year review of pain control during laser therapy using the flashlamp pulsed
      dye laser.
AB  - Laser therapy is now accepted as the treatment of choice for port wine stains.
      Patient reaction to laser light exposure and methods used to control pain during
      1357 treatment sessions for 350 medium to large port wine stains using the SPTL-1
      laser (Candela Laser Corporation) are reported. In the majority of cases (86%) it
      was necessary to use either general anaesthesia or some other form of local pain
      control.

PMID- 8149054
TI  - Measuring outcome in low-priority plastic surgery patients using Quality of Life
      indices.
AB  - 292 patients with a variety of "low-priority" conditions completed the Health
      Measurement Questionnaire self-report instrument (HMQ) on admission for surgery,
      and again 6 months post-operation. Comparison of the two questionnaires permitted
      the change in Quality of Life (QoL) to be measured. Overall, of the respondents,
      73% gained benefit from surgery in terms of improvement in QoL. The largest gains
      were in the breast surgery group, but there were individual patients in all
      groups who gained substantial improvement in QoL. The results suggest that the
      HMQ is a useful method of measuring benefit in patients admitted for low priority
      plastic surgery procedures.

PMID- 8149055
TI  - Outcome audit in plastic surgery: the Cambridge Classification.
AB  - Plastic Surgery Outcome Audit has until now been limited to studies of individual
      conditions. The Department of Plastic Surgery at Addenbrooke's Hospital,
      Cambridge, has developed an objective outcome classification applicable to all
      plastic surgery procedures. The four end-result categories--aesthetic appearance;
      physical function; tumour clearance; and surgical complications--are each graded
      in clear stages from 1 (excellent result) to 4 (result requiring re-operation) in
      a system which is easy to apply to every patient. The development and potential
      use of this classification are discussed. The Cambridge Classification is used in
      conjunction with diagnostic codes, which can be simple like the Logbook codes
      used by British Trainees or more complex, such as Read codes.

PMID- 8149056
TI  - A prospective investigation of the healing of grafted pretibial wounds with early
      and late mobilisation.
AB  - The aims of this study were to determine whether early mobilisation delays wound
      healing after meshed split skin graft repair of pretibial wounds and to identify
      other factors delaying the healing of these wounds. A prospective randomised
      controlled trial was conducted to compare the time to complete healing of
      patients mobilised early (the first postoperative day) against those who
      mobilised late (the tenth postoperative day). There was no difference in time to
      complete healing. Patients with a history of oral steroid therapy had a mean
      delay in wound healing of approximately 8 days (p < 0.02). The severity of tissue
      damage, as indicated by undermining of the skin margins, damage to the fascia and
      exposure of the periosteum, correlated with delayed wound healing (p < 0.05).

PMID- 8149057
TI  - Reconstruction of soft tissue defects of the lower leg with the distally based
      medial adipofascial flap.
AB  - A distally based medial adipofascial flap, based on the lower perforator
      originating from the posterior tibial vessels, is described. It has been used
      successfully to cover tibial bone and/or plate exposure on the lower leg in 5
      patients.

PMID- 8149058
TI  - Squamous cell carcinoma arising in a congenital naevus.
AB  - A case is presented in which an SCC arises within a congenital melanocytic naevus
      -a phenomenon which, to our knowledge, has not previously been described. It is
      more significant in that the area involved is a non-sun exposed area.

PMID- 8149059
TI  - Hypoglossia congenita with anterior maxillo-mandibular fusion.
AB  - Two cases of hypoglossia congenita with anterior maxillo-mandibular fusion are
      reported. One is a case of hypoglossia with anterior maxillo-mandibular fusion
      and the other is a case of hypoglossia-hypodactylia with anterior maxillo
      mandibular fusion. This condition presents the anaesthetist with the problem of
      airway management during the surgery. A simple technique using a nasopharyngeal
      tube was used for these two cases, with satisfactory results.

PMID- 8149060
TI  - Link pattern adipofascial flap.

PMID- 8149061
TI  - Neurocutaneous axial island flaps.

PMID- 8149062
TI  - Two end-to-side neurorrhaphies and nerve graft with removal of the epineural
      sheath: experimental study in rats.
AB  - We have studied a new type of end-to-side nerve repair in rats. The healthy
      (donor) nerve was not divided but an epineural window was created. In our
      experiment, a nerve graft bridged the tibial nerve to the distal end of the
      divided peroneal nerve. Electrophysiological studies showed electrical impulses
      conducted through both end-to-side nerve junctions. Histological studies
      demonstrated axons leaving the lateral surface of the healthy (donor) nerve.
      Based on these observations, we suggest that end-to-side neurorrhaphy from a
      healthy nerve may bridge a neural deficit.

PMID- 8149063
TI  - Squamous cell carcinoma of the pinna: a 6-year study.
AB  - Over a 6-year period, 54 sequential lesions of squamous cell carcinoma of the
      pinna were studied in 44 patients with regard to the side, clinical features and
      their duration, TNM clinicopathological classification, treatment and follow-up.
      Treatment delay, types of surgical procedures, anaesthesia and postoperative
      complications were all analysed. The overall incidence of residual and recurrent
      cancer was 25.92%. The regional lymph node recurrence was 9.26%, though only
      5.56% had clinically persistent cancer. Six patients subsequently died; two of
      these deaths were due to the cancer.

PMID- 8149064
TI  - Non-melanoma skin cancer in renal transplant recipients: the extent of the
      problem and a strategy for management.
AB  - Over the past 2 years, we have examined all patients with a functioning renal
      allograft attending a regional nephrology unit. A total of 291 patients were
      examined. 172 (59%) were found to have cutaneous warts, and 64 (21.9%) had non
      melanoma skin cancer (NMSC). The proportion of patients with both warts and NMSC
      increased with time from transplantation: 40% of patients who had been
      transplanted for more than 9 years had NMSC. Fifteen patients had extensive
      dysplastic change in all sun-exposed areas, particularly the dorsal aspect of the
      hands. This subgroup of patients develop large numbers of tumours, particularly
      squamous cell carcinomas (SCC), and require close surveillance and frequent
      surgery. One patient has died as a result of rapidly evolving metastases from an
      SCC on the dorsum of the hand. Excision and grafting of the backs of the hands in
      four patients, and long term etretinate therapy in 6 patients have led to a
      marked reduction in the frequency of surgery to remove tumours. The very high
      rate of NMSC, frequently multiple, found in this study of UK residents is a
      source of concern and indicates the need for close dermatological monitoring of
      allograft recipients, with intensive surveillance of patients with extensive
      dysplasia, who may develop tumours requiring surgery every few weeks.

PMID- 8149065
TI  - Surgical research, experimentation and innovation.

PMID- 8149066
TI  - Congenital breast asymmetry: subjective and objective assessment.
AB  - There is currently no standard objective method for the assessment of
      developmental breast asymmetry. The results of corrective surgery in 24 patients
      with congenital breast deformities were evaluated subjectively (symmetry scores
      by patients and panels of observers), and objectively (linear measurements of
      nipple position and stereophotogrammetrically determined breast volumes). The
      latter were obtained using a newly developed prototype computer based technique
      (Bodymap). This study is the first reported use of stereophotogrammetry in
      assessing results of surgery for the correction of congenital breast asymmetry.
      The results obtained, their clinical implications, and the usefulness of Bodymap
      in the objective measurement of breast asymmetry are discussed.

PMID- 8149067
TI  - [Spontaneous pneumothorax].

PMID- 8149068
TI  - [Minimal intervention in smoking in the outpatient pneumonology consultation].
AB  - Brief intervention (BI) in smoking has been shown to be an effective way of
      stopping smoking in the general population. BI involves medical advice given to
      each smoking patient, with complementary information on the effects of smoking on
      the body and methods of giving up the habit. Patients who come to the clinic with
      respiratory disease may be especially receptive to BI since the strong link
      between their symptoms and smoking may increase their motivation for cessation. A
      BI protocol on smoking was applied in 285 smokers seen in an outpatient
      pneumological clinic. Two hundred eight smokers (group A) received medical advice
      and health care education with the offer of follow up. Seventy-seven smokers
      (group B) received the same BI protocol, with the offer of support treatment with
      nicotine gum (2 mg) and an explanation as to its use. One year after BI the
      patients were contacted by telephone to determine the number of non-smokers, with
      the result adjusted according to the truth index (71.4%) known for telephone
      response in this context. A total of 71 (24.9%) smokers were not located by
      telephone due to change of address, wrong number, exitus or lack of telephone.
      The estimated number of non-smokers in group A was 31.5/160 (19.7%) and 8.6/54
      (15.9%) (non significant difference, chi square test). Group B's use of nicotine
      gum was therapeutically significant in 11.0% of the cases. We conclude that the
      efficacy of BI in the outpatient pneumological clinic is high.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8149069
TI  - [The description of a method for performing repeated evacuatory thoracentesis in
      patients with untreatable malignant pleural effusion].
AB  - Repeated drainage by thoracocentesis may be carried out in patients with
      untreatable malignant pleural effusion by subcutaneous insertion of an access
      system initially designed for the peritoneum. The catheter is inserted into the
      pleural cavity through thoracic tissue, facilitating repeated drainage with
      minimum risk for the patient with recurring malignant pleural effusion who is no
      longer eligible for other therapeutic procedures. We describe our initial
      experience in three patients with untreatable advanced neoplasms who received
      symptomatic treatment for dyspnea with this method on an out-patient basis for a
      period of between one to four months. No complications were observed except for
      partial obstruction of a catheter which was unblocked with urokinase.

PMID- 8149070
TI  - [The primary ciliary dyskinesia syndrome. A frequent pathology].
AB  - The prevalence of primary ciliary dyskinesia syndrome (PCDS) in Western countries
      is of 1/40,000 but is 13% in patients with bronchiectasis. The aim of this study
      was to determine the prevalence of PCDS in patients with bronchiectasis and
      sinusitis, including whether or not these patients present specific clinical
      signs. Eighteen patients with these two conditions from an area with 750,000
      inhabitants in Valencia (Spain), were studied for 2 years. Radiologic and
      clinical information was recorded and mucociliary motility was measured with
      albumin marked with radioactive technetium. The structure of the nasal mucosa
      cilia was also studied. In 14 patients (77%) mucociliary motility was suppressed
      and in 13 ultrastructural changes typical of PCDS were observed. Only male
      infertility and situs inversus were more frequent in patients with PCDS; other
      clinical signs were equally severe and frequent in patients with PCDS and in
      those in whom no cause for bronchiectasis and sinusitis could be found. We
      conclude that 1) the prevalence of PCDS in patients with bronchiectasis and
      sinusitis is 77%; 2) in these patients a test of mucociliary motility is
      sufficient for diagnosis (structural study not being required); 3) the prevalence
      of PCDS in our population seems to be greater than that described; and 4)
      clinical signs are similar in patients with PCDS and in those with bronchiectasis
      of unknown genesis.

PMID- 8149071
TI  - [The role of computed tomography (CT) of the thorax in defining the anatomical
      extent in bronchogenic carcinoma (BC)].
AB  - A series of 129 carriers of non-small cell bronchogenic carcinoma (BC), in whom
      computed tomography (CT) of the thorax was performed as part of the preoperative
      study, are presented. The results of CT were compared with those of thoracotomy
      in terms of sensitivity (SEN), specificity (SP), positive predictive value (PPV)
      and negative predictive value (NPV). Thoracic wall (prevalence 0.18): SEN, SP,
      PPV and NPV were 0.65, 0.92, 0.63 and 0.92, respectively. In peripheral tumors
      these values were 0.85, 0.90, 0.69 and 0.96, respectively. CT demonstrating
      invasion of the thoracic wall thus requires confirmation for the purpose of
      surgical staging. If CT reveals an intact wall, however, surgery may take place
      immediately. Malignant mediastinal lymph nodes: (prevalence 0.36): SEN, SP, PPV,
      and NPV were 0.70, 0.89, 0.78 and 0.84, respectively. For peripheral tumors these
      values were 0.78, 0.93, 0.82 and 0.91, respectively. CT demonstrating malignant
      mediastinal lymph nodes should be confirmed by mediastinoscopy. If mediastinal
      malignancy is not observed by CT, thoracotomy may be performed in peripherally
      located tumors; in centrally located tumors, however, the absence of adenopathy
      should be confirmed by mediastinoscopy.

PMID- 8149072
TI  - [Home mechanical ventilation: the current outlook].

PMID- 8149073
TI  - [The results of the surveys of the Lung Cancer Task Force of the Spanish Society
      of Pneumology and Thoracic Surgery (SEPAR)].
AB  - BACKGROUND: After its formation in 1991, the Lung Cancer Task Force of the
      Spanish Pneumology and Thoracic Surgery Society (SEPAR) wrote a list of Spanish
      research priorities as a basis for future multi-center studies. OBJECTIVES: 1) To
      obtain information on ways of diagnosing, treating and making decisions regarding
      patients with bronchogenic carcinoma; 2) to identify different attitudes toward
      bronchogenic carcinoma with homolateral mediastinal adenopathy (N2); 3) to sound
      out thoracic surgeons regarding their participation in nationwide collaborative
      studies on bronchogenic T3 and T4 carcinoma and obtain their views on concrete
      surgical questions; and 4) to study protocols for postoperative surveillance.
      MATERIAL AND METHODS: The Executive Committee took into consideration the
      contributions of Task Force members in writing four survey questionnaires. Survey
      1: "Ways of studying, treating and coming to decisions about patients with
      bronchogenic carcinoma." Survey II: "Diagnostic and therapeutic attitudes toward
      N2." Survey III: "Bronchogenic T3-T4 carcinoma." Survey IV: Postoperative
      assessment in bronchogenic carcinoma." Forty-seven, 43, 35 and 42 replies,
      respectively, were received. Analysis of evaluable replies provide the basis of
      the results. RESULTS: Survey I: The 47 replies came from 32 hospitals; 21 also
      sent copies of their diagnostic-therapeutic protocols, revealing 19 different
      models for clinical use (17) or research (2). SURVEY II: X-rays and computed
      tomography (CT) of the thorax are the non-invasive procedures used by most of the
      respondents (39 or 95%). Mediastinoscopy is indicated selectively according to 32
      (78%) and routinely according to 7 (17%). Twenty-eight (68%) respondents confirm
      N2 X-rays histologically and 9 (22%) resort immediately to surgery. Five (12%)
      exclude from surgery any N1 found by mediastinoscopy or mediastinotomy, while the
      others may exclude such patients depending on histological type, number and
      location of ganglia and type of mediastinal involvement. After induction
      chemotherapy in patients excluded from surgery, 24 (59%) may restore eligibility
      if some form of remission is observed. If N2 is found during thoracotomy, 25
      respondents (61%) follow with pulmonary resection and mediastinal
      lymphadenectomy, although they first take into account mainly patient
      operability, likelihood of a complete resection, tissue type, invasion of the
      gangliar capsule and the number of malignant nodes found. SURVEY III: Twenty
      seven, or a 98% majority of the 29 evaluable respondents, said that they would be
      in favor of a national register of T3-T4 carcinoma, would use a computerized
      system for recording case histories and would follow a standard therapeutic
      protocol. All believe that resection of the pleura and the costal wall and
      intercostal space is useful; slightly more than half believe that it would be
      useful to extend resection to the trachea and carina, superior vena cava or
      atrium. Eight (30%), 11 (41%) and 12 (44%) favor resection of the vertebral body,
      muscle wall of the esophagus and the pulmonary artery, respectively. Twenty-four
      (83%) place no faith in partial surgery in cases of T3 and T4. SURVEY IV: Thirty
      (96%) of the 31 thoracic surgeons who answered the questionnaire follow their
      patients after surgery, while only 7 (63%) of the 11 pneumologists do so. Thirty
      four (80%) use a postoperative follow-up protocol and 29 (69%) note the tumor
      free interval. Twenty-three (54%) make a functional assessment of the patient and
      26 (62%) order blood and biochemical work-ups. There is little agreement on the
      use of tumoral markers and only 6 (14%) do immunological studies occasionally.
      All use simple chest X-rays routinely; CT, abdominal sonograms and bone
      gammagrams may be used, depending on clinical data and physical examination. Most
      (36 or 85%) believe that collaboration on a postoperative protocol for nationwide
      use would be useful. (ABSTRACT TRUNCATED)

PMID- 8149074
TI  - [Tracheobronchial involvement in non-Hodgkin's lymphoma].
AB  - Tracheobronchial involvement in non-Hodgkin's lymphoma (NHL) has been little
      described. We present two patients with NHL and endobronchial involvement of
      different characteristics. In the first case diffuse involvement of the bronchial
      mucosa was observed in the context of a systemic NHL of 10 years' duration. In
      the second patient, endobronchial involvement consisted of a mass obstructing the
      trachea and the right main bronchus which was the first manifestation of
      lymphoma.

PMID- 8149075
TI  - [Antibiotic therapy in the acuity of COPD: yes or no?].

PMID- 8149076
TI  - [Endobronchial inflammatory pseudotumor. A case report and review of the
      literature].
AB  - The endobronchial inflammatory pseudotumor is a little described variant of
      inflammatory lung pseudotumor, the growth of which is directed towards bronchial
      lumen. A case is presented and seventeen other well documented cases from the
      medical literature are reviewed. This variant has been frequently observed with
      clinical manifestations of obstructive respiration and atelectasis as a
      radiologic pattern allowing detection at an early age. Endoscopy does not usually
      confirm diagnosis; surgery and study of the specimen removed is therefore
      necessary.

PMID- 8149077
TI  - [Bronchial asthma or the sick building syndrome?].

PMID- 8149078
TI  - [Left lower lobectomy by video-assisted surgery].

PMID- 8149079
TI  - [Silicosis in the granite industry].

PMID- 8149080
TI  - [Pneumothorax and acupuncture].

PMID- 8149081
TI  - [Adenosine deaminase activity in the pleural effusion. A study of 64 cases].
AB  - Clinical and analytic data of 64 patients with firm etiologic diagnosis of
      pleural effusion with adenosine deaminase (ADA) present, were analyzed
      retrospectively. The patients had entered our hospital over a 40-month period.
      ADA activity in pleural fluid was analyzed by the Blake and Berman kinetic
      method. Mean ADA activity of the total sample was 32 U/l (SD:23.9). In patients
      with tuberculous pleural effusion ADA activity was higher than in the remaining
      patients (47.7, SD:21.4, versus 15.5 SD: 13.2; p < 0.0001). In the group of
      patients with tuberculous pleuritis diagnosed by pleural biopsy (22 cases) the
      presence of necrotizing granulomas was associated with slightly higher ADA
      activity although the difference was not statistically significant (49.2 SD 10.1
      versus 41.3 SD 8.9; p = 0.07). Among only patients with tuberculous pleuritis or
      neoplasia with lymphocytic exudate, a cut off point greater than 23 U for ADA
      predicted a diagnosis of tuberculous pleuritis with a sensitivity of 0.96,
      specificity of 1, positive predictive value of 1, negative predictive value of
      0.94, and a confidence limit of 0.97. In conclusion, ADA activity greater than 23
      U determined by the kinetic method in pleural fluid with signs of lymphocytic
      exudate is strongly suggestive of pleural tuberculosis based on our sample of
      patients with pleural effusion.

PMID- 8149082
TI  - "New" causes of heart disease and stroke.
AB  - I have discussed 10 "new" diseases. Some produce heart disease, some produce
      strokes, and some may produce both heart disease and stroke. It is of great
      interest to me that some of them are due not to nature's ravages but to the
      ingestion of agents such as toxic oil, L-tryptophan, ergot, adriamycin, and
      psychotropic drugs. I classify these man-made diseases as "environmental"
      diseases. Use of some of the offending agents cannot be justified; for example,
      toxic oil and L-tryptophan are not needed. On the other hand, drugs such as ergot
      preparations are extremely useful when used properly.

PMID- 8149083
TI  - Cerebral venous thrombosis.

PMID- 8149084
TI  - The value and limitations of cardiac enzymes in the recognition of acute
      myocardial infarction.
AB  - Assay of plasma enzymes, particularly creatine kinase isoenzymes and isoforms,
      provides sensitive and specific criteria for the diagnosis of acute myocardial
      infarction. Recent advances offer particular promise of very early detection of
      infarction, noninvasive and prompt recognition of coronary recanalization, and
      detection of early recurrent infarction.

PMID- 8149085
TI  - Practical aspects of cardiac resuscitation.

PMID- 8149086
TI  - Surgical treatment of cardiac arrhythmias.
AB  - Surgical treatment of cardiac arrhythmias will continue to evolve as advances in
      understanding of the mechanisms of these arrhythmias and technological
      developments in the areas of mapping and noninvasive diagnostic capabilities are
      made. As limitations with many aspects of pharmacological therapy become more
      apparent, surgical therapies will continue to play a pivotal role in the
      definitive treatment of these supraventricular and ventricular tachyarrhythmias.

PMID- 8149087
TI  - Are triglycerides important as a risk factor for coronary disease?

PMID- 8149088
TI  - The role of speech therapy in stroke rehabilitation.

PMID- 8149089
TI  - Tips for smoking cessation.

PMID- 8149090
TI  - The athletic heart.

PMID- 8149091
TI  - Intracerebral hemorrhage.

PMID- 8149092
TI  - Recognition and management of mitral stenosis.
AB  - Mitral stenosis may be recognized simply on routine physical examination from
      abnormalities on auscultation, which are subsequently confirmed by Doppler
      echocardiographic examination. The diagnosis may also be suspected in patients in
      whom the history is suggestive of rheumatic fever and in whom physical diagnosis
      reveals findings indicative of mitral stenosis. Occasional cases of mitral
      stenosis are picked up in the Doppler echocardiography laboratory when a patient
      has not been suspected of having mitral stenosis but in whom a routine
      echocardiogram has been taken, for whatever reason. If there is any doubt about
      the presence of mitral stenosis, confirming the presence of a diastolic pressure
      gradient across the mitral valve during cardiac catheterization permits one to
      make a definitive diagnosis as well as estimate the area of the stenotic valve
      orifice. Intervention with either surgery or balloon valvotomy is indicated when
      the mitral valve area falls to < or = 1.2 cm2 in a symptomatic patient.

PMID- 8149093
TI  - Stroke symptoms associated with migraine headaches.

PMID- 8149094
TI  - Systolic murmurs.

PMID- 8149095
TI  - Essential workup of the hypertensive patient.

PMID- 8149096
TI  - The role of transcranial Doppler ultrasound in assessing cerebrovascular disease.

PMID- 8149097
TI  - When to refer a patient for transesophageal echocardiography.

PMID- 8149098
TI  - The "Shaggy" aorta.

PMID- 8149099
TI  - The cardiovascular effects of cocaine.

PMID- 8149101
TI  - Varicose veins in the lower extremities.

PMID- 8149100
TI  - Recognition and management of pulmonary embolism.

PMID- 8149102
TI  - Excitation-contraction-relaxation coupling in the normal and failing heart.

PMID- 8149103
TI  - Of mouse and man: molecular switches that control cardiac growth and development.

PMID- 8149104
TI  - Growth factors and the vessel wall.
AB  - The vascular tree is a highly specialized organ that has developed a complex and
      highly orchestrated mechanism of response to injury and stress. After PTCA-like
      injury many of these mechanisms are activated to maintain vessel integrity.
      Similar but clearly different growth mechanisms are activated by hypertension and
      hemodynamic stress. In this light, restenosis is merely a reparative response
      that has gone on too long or to a greater extent than necessary. The number of
      growth factors that affect this system is enormous, and their temporal and
      spatial distribution suggests that therapy targeted to any single factor is
      unlikely to be successful. In contrast, therapies directed at common mediators
      such as extracellular matrix and downstream cellular effectors may be more
      effective. Increasing knowledge of these interactions should point the way to new
      therapies based on cell-cell and cell-matrix interactions that are tissue
      specific and focused in time and that take advantage of the common mechanisms by
      which vessels normally adapt to stress.

PMID- 8149105
TI  - Angina pectoris: words patients use and overlooked precipitating events.
AB  - Routine questioning may be inadequate to identify angina pectoris or prolonged
      discomfort due to myocardial ischemia. The clinician must ask patients if they
      have had any unpleasant sensations in the chest, neck, throat, jaw, arms, elbow,
      wrist, or back that they have not noticed previously. Once the patient uses a
      word to describe the discomfort, the physician should use the same word and
      inquire about the duration of the discomfort and precipitating causes, including
      the less common and unusual ones discussed in this editorial.

PMID- 8149106
TI  - Limiting the size of myocardial infarction by early coronary artery reperfusion.

PMID- 8149107
TI  - Diastolic murmurs.

PMID- 8149108
TI  - Lessons learned from deinstitutionalisation in the US.
AB  - Deinstitutionalisation is at an advanced stage in the US, both in duration, and
      in reduction in state hospital beds. The new generation of chronically and
      severely mentally ill persons has posed the greatest problems. They no longer
      receive life-long hospital admission and thus permanent asylum from the demands
      of the world. Resistance to treatment and substance abuse are problems. Early
      proponents of deinstitutionalisation believed it would be cheaper, better, and
      give the mentally ill their freedom. In reality, good community care does not
      cost less. While a number of community programmes in the US have been impressive,
      they have served only a small proportion of the total population of severely
      mentally ill persons. More freedom has been of benefit for many, but has proved
      difficult for some patients. Some patients have been deinstitutionalised who
      cannot be effectively treated in the community. The homeless mentally ill
      epitomise all these problems.

PMID- 8149109
TI  - Evidence for autosomal dominant transmission in Tourette's syndrome. United
      Kingdom cohort study.
AB  - Complex segregation analyses were performed on families ascertained through 40
      unselected consecutive patients with Tourette's syndrome to examine the
      hypothesis that its transmission is consistent with genetic inheritance. Analyses
      were done using several diagnostic classifications. All results were consistent
      with an autosomal dominant gene with high penetrance. The penetrances ranged from
      0.882 to 1.000 for males and 0.452 to 0.980 for females, depending upon the
      specific classification scheme incorporated into the analyses.

PMID- 8149110
TI  - A placebo-controlled trial of d-fenfluramine in bulimia nervosa.
AB  - d-Fenfluramine is a 5-HT agonist which decreases food intake and excessive
      carbohydrate intake in humans. A placebo-controlled trial of d-fenfluramine (45
      mg/day) was conducted in 43 patients with bulimia nervosa. The patients entered
      an eight-week trial of medication during which they also received cognitive
      behavioural therapy. Treatment response was assessed using food diaries to record
      eating behaviour, and self-rating questionnaires to measure psychopathology. The
      drug trial, and a follow-up assessment after a further eight weeks, were
      completed by 39 patients. Abnormal eating behaviour and psychopathology improved
      significantly in both the d-fenfluramine and placebo groups during the treatment
      trial. The study failed to show that the addition of d-fenfluramine affords an
      advantage over brief psychotherapy alone. Although d-fenfluramine is effective in
      suppressing the overeating, excessive snacking, and excessive carbohydrate
      consumption which are frequently found in overweight or obese patients, this
      study suggests that the drug is not an effective treatment for bulimia nervosa.

PMID- 8149111
TI  - Mood and psychiatric disturbance in HIV and AIDS: changes over time.
AB  - A sample of 26 HIV seronegative, 59 HIV seropositive asymptomatic and 7 HIV
      seropositive symptomatic homosexual and bisexual men were assessed over two
      visits, a mean of 11 months apart, using the BDI, STAI, and CIS. Significant
      differences emerged between the symptomatic group and the other two groups. Past
      psychiatric history and the somatic items in the assessments accounted for some
      of these differences. The seropositive asymptomatic and the seronegative groups
      did not differ on any of the mood or psychiatric assessments, suggesting minimal
      effect on psychological well-being of seroconversion in the absence of symptoms.

PMID- 8149112
TI  - Quality of life for patients detained in hospital.
AB  - The quality of life of detained patients has not received adequate attention
      despite the responsibilities placed on hospital staff and the special problems
      faced by these patients. Legal principles to ensure quality of life have not been
      formalised, and the acceptable standards that a patient can expect have not been
      tested in the UK courts. Contemporary models of ensuring quality are being
      imposed with increasing pressure on health care professionals, but high-quality
      management has sometimes lagged behind. This has led to a poor quality of life
      for certain patients. It is important for future research to overcome
      difficulties in developing objective measurements and set the appropriate
      standards of quality of life that detained patients should expect. This would
      provide a basis against which both appropriate standards of care and the
      necessary resource allocation could be measured.

PMID- 8149113
TI  - Diagnostic agreement in psychiatry. A comparative study between ICD-9, ICD-10 and
      DSM-III-R.
AB  - A random sample of 100 new patients referred consecutively to the psychiatric
      hospital was assessed using the Arabic translation of the PSE. An abstract form
      was designed to include all PSE scores as well as the necessary extra data to
      make ICD-9, ICD-10, and DSM-III-R diagnoses. Kappa correlation was calculated for
      inter-rater and intra-rater reliability. Overall reliability and reliability of
      each major psychiatric diagnosis were compared between the three systems. The use
      of the PSE helped in achieving good agreement between Arab psychiatrists for all
      the three systems, but ICD-10 was found to have the highest reliability figures
      both for three-digit and four-digit psychiatric diagnoses.

PMID- 8149114
TI  - Child and adult depression: a test of continuities with data from a family study.
AB  - The summaries of clinical data on children attending the Maudsley Hospital during
      the years 1968-72 were used to identify 80 children meeting operational criteria
      for depression, and 80 matched psychiatric control children. At follow-up, on
      average 18 years after the initial contact, information was obtained on the adult
      outcomes of 62 of the depressed children and 69 of the controls. At least one
      first-degree relative of 111 (85%) of these probands was interviewed; the great
      majority of interviews with relatives were conducted 'blind' to the proband's
      symptoms in both childhood and adulthood. The lifetime prevalence of RDC
      depression was significantly higher in the 128 interviewed relatives of the
      depressed children than in the 151 relatives of the controls. Higher rates of
      depression were found among the female relatives of both the depressed and
      control probands. These findings suggest that depression in young people
      resembles depression in adults in two key respects: it tends to run in families,
      and there are higher rates of depression among the female than among the male
      first-degree relatives.

PMID- 8149115
TI  - Lithium augmentation therapy in tricyclic-resistant depression. A controlled
      trial using lithium in low and normal doses.
AB  - Thirty-four patients with tricyclic-resistant depressive illness took part in a
      nine-week, double-blind, placebo-controlled trial of lithium augmentation. In
      addition to the maximum tolerated doses of their tricyclic antidepressant, the
      experimental group (n = 16) received 250 mg lithium daily for three weeks,
      followed by 750 mg lithium daily for six weeks, while the controls (n = 18)
      received placebo for three weeks followed by three weeks each of 250 mg lithium
      daily and 750 mg lithium daily. There was no significant difference between
      placebo and 250 mg lithium for weeks 0-3 of the trial. However, there was a
      significantly greater improvement on the MADRS for weeks 3-6 for those subjects
      on 750 mg lithium than for those on 250 mg lithium. In addition, using a 50% fall
      in the HRSD as a criterion of drug responsiveness, 22% responded to placebo, 18%
      to 250 mg lithium, and 44% to 750 mg lithium. Thus, lithium in normal, but not in
      low, dose has a significant antidepressant effect in TCA-resistant depression.
      Further controlled studies using lithium in normal dose in trials which have a
      greater duration of placebo exposure are required to confirm the lithium
      augmentation effect.

PMID- 8149116
TI  - An affective syndrome in psychopaths with borderline personality disorder?
AB  - A preliminary study of the repetitive mood swings of 72 female psychopaths with a
      DSM-III diagnosis of borderline personality disorder demonstrated considerable
      complexity and specificity in what has been previously considered a criterion of
      personality disorder. A principal-components analysis of the symptom profile for
      these affective disturbances revealed four factors (anxiety, anger, depression,
      and tension) which showed individual patterns of association with additional
      lifetime diagnoses of major mental illness and other personality disorders. The
      women also had multiple mood-related behavioural disorders, enacted with a
      feeling of compulsion, which appeared to relieve the original affective symptoms.
      It is hypothesised that these women could have a distinct affective syndrome that
      has not previously been described in the literature.

PMID- 8149117
TI  - Impaired in vivo immune responses in patients with melancholia.
AB  - Previous attempts to establish a relationship between impaired cell-mediated
      immunity (CMI) and major mood disorders have been limited by a failure to explore
      the relevance of depressive subcategories or to assess CMI by in vivo methods. In
      this case-control study CMI was assessed in 57 patients with major depression (31
      with melancholic, 26 with non-melancholic disorders), and in age- and sex-matched
      controls by both in vitro and in vivo immunological techniques. Compared with
      control subjects and patients with non-melancholic depression, patients with
      melancholia demonstrated reduced in vivo CMI as assessed by delayed-type
      hypersensitivity (DTH) skin responses. Although increasing age, severity of
      depression, hospital admission for treatment, and reported weight loss are
      correlates of melancholia, none of these factors alone, or in combination,
      accounted for the differences in DTH responses observed between the two
      depressive subtypes. These data suggest that impaired CMI in vivo may be limited
      to those with melancholic disorders. At this stage the factors which account for
      this effect are unclear.

PMID- 8149118
TI  - Sex and schizophrenia: effects of diagnostic stringency, and associations with
      and premorbid variables.
AB  - In a case-record study, all first-contact patients with non-affective functional
      psychosis from a defined area over 20 years were diagnosed according to
      operational criteria of varying stringency and emphasis, and incidence rates for
      each set of criteria determined by sex and age at onset; data on premorbid
      adjustment were also analysed by sex and age at onset. The overall first-contact
      incidence of non-affective functional psychosis was approximately equal in men
      and women; however, the ratio of male to female incidence rates rose
      progressively when RDC (1.2), DSM-III-R (1.3), DSM-III (2.2), and Feighner (2.5)
      criteria for schizophrenia were applied. Schizophrenia was most common in young
      males and least common in older males, with females occupying an intermediate
      position. Schizophrenia in young males, particularly when stringently defined,
      was especially likely to be associated with single status, poor work and social
      adjustment, and premorbid personality disorder. The results suggest that
      schizophrenia syndrome is heterogeneous, and young males are especially prone to
      a severe neurodevelopmental form of illness associated with premorbid deficits.

PMID- 8149119
TI  - Age of onset in schizophrenia: relations to psychopathology and gender.
AB  - This retrospective study evaluated differences between patients with first
      manifestation of schizophrenic psychosis (ICD 295) or paranoid syndrome (ICD 297)
      between the ages of 18 and 23 or 40 and 63 years. Gender-specific variations in
      psychopathology were also examined. The numerous analyses of variance gave few
      significant differences. Patients with a late onset of the disease scored higher
      on depressive and autonomic syndrome scales at admission, whereas patients with
      an early onset showed more psychosocial impairment at discharge and their stay in
      hospital was longer. Among schizophrenic patients only (ICD 297 excluded), only
      the higher score for autonomic syndrome of the older patients at admission was
      confirmed. Men were more apathetic at admission and discharge than were women.
      Excluding patients with a paranoid syndrome, these differences were again
      significant. Moreover, schizophrenic men had higher depressive and psycho-organic
      syndrome scores at discharge. The demonstration of only marginal differences
      between early- and late-onset schizophrenia does not support the assumption that
      age of onset markedly influences psychopathology.

PMID- 8149120
TI  - Psychiatric morbidity in the first-degree relatives of schizophrenic patients.
AB  - First-degree relatives (FDRs) of 162 schizophrenic and 106 control probands were
      investigated [corrected]. Psychiatric morbidity was present in 34.8% of FDRs of
      schizophrenic probands and in 9.2% of FDRs of controls. There was significantly
      more psychiatric illness in the siblings and parents than in the offspring of
      both schizophrenic and control subjects. The morbidity risks for schizoid
      schizotypal personality disorders, cannabis-use disorder and paranoid personality
      disorder were significantly higher in the FDRs of schizophrenic patients than in
      those of controls, suggesting a biological relationship.

PMID- 8149121
TI  - Compulsory treatment for anorexia nervosa: compassion or coercion?

PMID- 8149122
TI  - Sex reassignment surgery. A study of 141 Dutch transsexuals.
AB  - "This is an evaluation of the therapeutic effect of sex reassignment surgery on
      36 female-to-male transsexuals and 105 male-to-female transsexuals in the
      Netherlands. Data were collected by means of structured interviews. The
      evaluation was made on the basis of subjective data only, that is on what the
      persons themselves reported on their gender identity, gender role, and physical
      condition. Allowing for the restrictive methodology of the (ex post facto) study,
      it is concluded that there is no reason to doubt the therapeutic effect of sex
      reassignment surgery. No specific differences were found between those who were
      still in medical treatment and those who had completed treatment. The findings
      obtained in the female-to-male transsexuals compare favourably with those
      obtained in male-to-female transsexuals. Finally, the conclusion is drawn that
      more attention ought to be paid to psychosocial guidance in addition to medical
      guidance."

PMID- 8149123
TI  - Clozapine-induced agranulocytosis treated with granulocyte macrophage colony
      stimulating factor.
AB  - Clozapine-induced agranulocytosis is usually reversible after discontinuation of
      the drug. A patient who developed agranulocytosis after termination of clozapine
      therapy responded to treatment with granulocyte macrophage colony stimulating
      factor.

PMID- 8149124
TI  - Concurrent agranulocytosis and hepatitis secondary to clomipramine therapy.
AB  - A 67-year-old man developed concurrent severe agranulocytosis and elevation of
      hepatic transaminases as a result of treatment with clomipramine. Although such
      adverse drug reactions can be considered rare events, the potentially serious
      nature of these reactions vindicate the routine monitoring of blood picture, and
      liver function tests, after initiation of treatment with tricyclic
      antidepressants.

PMID- 8149125
TI  - Lithium neurotoxicity at normal therapeutic levels.

PMID- 8149126
TI  - Capgras' syndrome presenting with violence following heavy drinking.
AB  - Two cases of Capgras' syndrome are described in which patients committed serious
      acts of violence towards family members who had become the subject of delusional
      misidentification. The cases illustrate some typical features of Capgras'
      syndrome including its potential for dangerousness. Intoxication with alcohol is
      proposed as a precipitant for violence in these patients.

PMID- 8149128
TI  - Psychiatry is more than a science.

PMID- 8149127
TI  - Face-processing impairments and the Capgras delusion.
AB  - Investigations of two cases of the Capgras delusion found that both patients
      showed face-processing impairments encompassing identification of familiar faces,
      recognition of emotional facial expressions, and matching of unfamiliar faces. In
      neither case was there any impairment of recognition memory for words. These
      findings are consistent with the idea that the basis of the Capgras delusion lies
      in damage to neuro-anatomical pathways responsible for appropriate emotional
      reactions to familiar visual stimuli. The delusion would then represent the
      patient's attempt to make sense of the fact that these visual stimuli no longer
      have appropriate affective significance.

PMID- 8149129
TI  - Psychiatry is more than science.

PMID- 8149130
TI  - Blood-letting in bulimia nervosa.

PMID- 8149131
TI  - Neglect of anger in Western psychiatry.

PMID- 8149132
TI  - Computerised assessment of depression in the medically ill.

PMID- 8149133
TI  - Insight in psychosis.

PMID- 8149134
TI  - Down's syndrome, longevity, and Alzheimer's disease.

PMID- 8149135
TI  - Association of schizophrenia and Duchenne muscular dystrophy.

PMID- 8149136
TI  - Quality of life in cancer patients: whose business is it anyway?

PMID- 8149137
TI  - Quality of life--a measure of the quality of nursing care?
AB  - Quality of life is a very complex phenomenon in the life of cancer patients.
      Individual perceptions might change with the state of disease and with necessary
      interventions. Some definitions seem to be more useful in cancer care than
      others. There has been considerable controversy in the quantity versus quality
      debate. Some confusion in the measurement of quality of life concerns
      "objectivity and subjectivity", referring either to the content of information or
      to persons other than the patient eliciting it. The relation between quality of
      life and quality of care has to be further explored: some dimensions of care
      might be of little or of potential relevance to the patient's quality of life.
      The dimensions of proven relevance concern psychological well-being through, for
      example, promotion of self-care or an enhanced perception of self-worth. These
      findings emphasise the importance of the concept of care, which is the essence of
      nursing. Contemporary professional and political difficulties require critical
      analysis.

PMID- 8149138
TI  - Bacterial resistance: new threats, new challenges.
AB  - Bacterial resistance remains a major concern. Recently, genetic transfers from
      saprophytic, non-pathogenic, species to pathogenic S. pneumoniae and N.
      meningitidis have introduced multiple changes in the penicillin target molecules,
      leading to rapidly growing penicillin resistance. In enterobacteriaceae, a
      succession of minute mutations has generated new beta-lactamases with
      increasingly expanded spectrum, now covering practically all available beta
      lactam antibiotics. Resistance emerges in the hospital environment but also, and
      increasingly, in the community bacteria. Widespread resistance is probably
      associated with antibiotic use, abuse and misuse but direct causality links are
      difficult to establish. In some countries as in some hospitals, unusual
      resistance profiles seem to correspond to unusual antibiotic practices. For
      meeting the resistance challenge, no simple solutions are available, but combined
      efforts may help. For improving the situation, the following methods can be
      proposed. At the world level, a better definition of appropriate antibiotic
      policies should be sought, together with strong education programmes on the use
      of antibiotics and the control of cross-infections, plus controls on the
      strategies used by pharmaceutical companies for promoting antibiotics. At various
      local levels, accurate guidelines should be adapted to each institution and there
      should be regularly updated formularies using scientific, and not only economic,
      criteria; molecular technologies for detecting subtle epidemic variations and
      emergence of new genes should be developed and regular information on the
      resistance profiles should be available to all physicians involved in the
      prevention and therapy of infections.

PMID- 8149139
TI  - Psychosocial aspects of cancer pain.
AB  - Pain, and especially cancer pain, is not a pure nociceptive, physical experience,
      but involves different dimensions of man, such as personality, affect, cognition,
      behavior and social relations. Cancer pain is best conceptualized as the
      convergence of multiple activated systems with feedback mechanisms to a complex,
      multidimensional model. The psychosocial aspects of this multidimensional model
      will be analyzed with special emphasis on results from recent research. Although
      most research has been conducted on the role of affect and cognition in cancer
      pain, data on other factors such as personality, behavior or social aspects exist
      and will be presented. In the second part of this paper the implications of these
      results for therapeutic strategies in clinical work will be discussed. Although a
      considerable body of knowledge exists to support the hypothesis of a
      multidimensional model of cancer pain, where psychosocial variables play an
      important role, only a few studies address the issue of to what degree different
      factors exercise their influence. This may be different from patient to patient
      and may change over the course of the disease. Whatever importance these single
      variables in the multidimensional model of cancer pain may have, the patient is
      best treated when none of these aspects is neglected in the assessment and all
      are taken care of in the treatment. A multidisciplinary team, with a psychiatrist
      as one of the team members, is often best prepared to fulfill this task.

PMID- 8149140
TI  - Cardiopulmonary resuscitation in medical cancer patients: the experience of a
      medical intensive-care unit of a cancer centre.
AB  - This study aimed to determine the effectiveness and potential indications of
      cardiopulmonary resuscitation (CPR) in medical cancer patients, by retrospective
      analysis of the records of the patients admitted between November 1985 and
      January 1992 in the medical intensive-care unit of a cancer hospital following
      cardiac arrest. Cardiac arrest occurred in 49 cancer patients. CPR was successful
      in 19 (39%) but only 5 (10%) were discharged alive from the hospital. CPR was
      successful in all 8 patients in which cardiac arrest was the consequence of an
      acute cardiovascular drug toxicity, even if the cancer was metastatic and the
      purpose of treatment not curative, while it was effective in only 25% of those
      where cardiac arrest was an ultimate complication of various problems such as
      septic shock or respiratory failure complicating the neoplastic disease. The
      results suggest that in cancer, as in other types of disease, CPR is mainly
      indicated when cardiac arrest is the consequence of an acute insult.

PMID- 8149141
TI  - Oral acyclovir as prophylaxis for bacterial infections during induction therapy
      for acute leukaemia in adults. The Leukemia Group of Middle Sweden.
AB  - We prospectively tested the hypothesis that prevention of herpes simplex virus
      infection with acyclovir might also reduce the incidence of bacterial infections
      in adult patients with acute leukaemia. During the first induction therapy a
      double-blind, randomized and placebo-controlled study was undertaken. Fifty-two
      patients were treated with 200 mg acyclovir orally four times daily throughout
      the induction period, whereas 55 patients received placebo. The groups were
      comparable with regard to age, cytotoxic chemotherapy and duration of
      neutropenia. Bacteraemias were significantly fewer in the acyclovir group (20
      versus 41 episodes; P = 0.007). The number of isolated microorganisms causing
      bacterial or fungal infections was also lower during acyclovir prophylaxis (52
      isolates, versus 93 isolates; P = 0.02). There was no significant difference
      between the groups with regard to the number of clinically documented infections
      or fevers of unknown origin. Herpes simplex virus isolations occurred only in the
      placebo group (P = 0.001). Thus, oral acyclovir prophylaxis was associated with
      reductions of all microbiologically documented infections suggesting that
      prevention of herpes simplex virus reactivation in acute leukaemia patients may
      reduce the occurrence of other infections.

PMID- 8149142
TI  - Caring for severely ill cancer patients. A comparison of working conditions in
      hospital-based home care and in hospital.
AB  - The goal of the study was to compare working conditions in a hospital with the
      conditions in a specialized hospital-based home care (HBHC) unit, which aims to
      replace hospital care for patients in need of institutional car. Staff (doctors
      included) in a HBHC unit (n = 35) and on three hospital wards (n = 113)
      participated in the study. All staff members worked regularly with severely ill
      cancer patients. Question about stress, job satisfaction and working conditions
      were asked in a self-administered questionnaire. Both groups showed a limited
      degree of continuous stress and a high degree of job satisfaction. Thus, the
      overall perception was than the working conditions were good. When significant
      differences were found, the responses of the HBHC staff were more positive. This
      included items such as more freedom to make their own decisions (P < 0.001),
      better co-operation between day and night shifts (P < 0.001), a more reasonable
      work load (P = 0.0001), fewer problems in communication with patients (P <
      0.001), and fewer problems with tension (P < 0.05) and with sleeping (P < 0.05).
      The findings may be due to several factors: the HBHC staff were older, more often
      married, had more children, had worked longer in health care and were thus more
      experienced. Complementary explanations may be continuous education within the
      HBHC and an organization stimulating the staff's own initiative, but also capable
      of supporting when necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149143
TI  - Cancer patients and their network: the meaning of the social network and social
      interactions for quality of life.
AB  - A lot of research is carried out on the subject of social relations and quality
      of life. One should find at least some indication for an association between the
      social environment and quality of life of cancer patients; will interventions be
      appropriate and well-considered? But until now, less has been known about the
      association between the social network of cancer patients and their quality of
      life. In this study, the way in which the patients' network can effect their
      quality of life is examined. Two patient groups are distinguished: a group of
      cancer patients recently treated for their cancer by surgery and a group treated
      by chemotherapy (n = 108 and n = 109) and these are compared with a disease-free
      group of cancer patients (n = 192). Although an association between network,
      social relations and quality of life is found, only a small part of the variation
      in quality of life can be explained by this social component. It seems that the
      cancer itself and the cancer treatment mainly affect the patients' quality of
      life and that the impact of the social environment is less significant.

PMID- 8149144
TI  - Blindness secondary to prostate cancer.
AB  - We report a case of blindness, secondary to hormone-refractory prostate cancer,
      occurring 7 years after the diagnosis of metastatic prostate cancer and 3.5 years
      after the clinical onset of the hormone-refractory state. Prolonged suppression
      of the disease with chemotherapy may have contributed to the unusual clinical
      findings. We discuss the role of supportive care in the management of prostate
      cancer.

PMID- 8149145
TI  - Management of bleeding in a patient with colorectal cancer: a case study.
AB  - Superficial bleeding in patients with malignant disease is a distressing symptom,
      which is often difficult to control. The following is a case study outlining the
      use of Sucralfate, an oral cytoprotective agent, used topically in a patient with
      colo-rectal cancer. The treatment resulted in control of bleeding, less localized
      pain and more freedom and independence for the patient.

PMID- 8149146
TI  - Two-stage incisor transplant and orthodontic space redistribution.
AB  - This report describes a complex case with unerupted upper anterior teeth and
      other dental anomalies requiring the two-stage incisor transplantation technique
      in conjunction with two phases of orthodontic treatment. The case illustrates the
      benefits of careful planning and of limiting treatment goals to the needs and
      perceptions of the patient. The final result also emphasizes the aesthetic dental
      improvements now possible with a multidisciplinary approach.

PMID- 8149147
TI  - SEM analyses of repaired glass-ionomer cements.
AB  - This study assessed the nature of the adhesion in repaired glass-ionomer
      restorative materials. Two chemically different glass-ionomer cements, Ketac Fil
      and Chemfil II Cap, and three different methods of conditioning the surface for
      repair were employed. Specimens of each material were prepared and the cut
      surfaces were then treated with either 35% phosphoric acid, 35% polyacrylic acid
      or a combination of phosphoric acid followed by polyacrylic acid. Freshly mixed
      material was injected against these treated surfaces and allowed to set under
      simulated intraoral conditions. The specimens were tested to failure in flexion
      after seven days storage. Assessment of the fractured surfaces was then carried
      out using the scanning electron microscope. The results showed the occurrence of
      both adhesive and cohesive failure.

PMID- 8149148
TI  - Effect of bleaching on vital discoloured teeth--a colorimetric evaluation in
      three patients.
AB  - Vital bleaching is considered effective for reduction of tooth discolouration.
      This evaluation was to measure colour changes before and after bleaching of vital
      tetracycline-discoloured teeth in three patients. Vital bleaching of their
      anterior maxillary teeth was performed five times at weekly intervals. Tooth
      colour was measured with a small-area colorimeter before, immediately and two,
      four and six months after bleaching. The results were expressed in the CIE L*a*b*
      colour system. The L* value, a lightness variable, increased after bleaching. The
      a* value changed only negligibly, but the b* value decreased after bleaching
      showing changes in the tooth colour from yellow to blue. The colour differences
      before treatment and six months after bleaching was visually perceivable.

PMID- 8149149
TI  - A new surgical approach to correcting mandibular prognathism in Oriental
      patients: report of two cases.
AB  - Surgical procedures had been used for the reduction of mandibular prognathism to
      achieve improved function and aesthetics. However, in Oriental patients
      mandibular prognathism was often present together with maxillary protrusion.
      Mandibular set-back surgery alone could not achieve the desired aesthetics in
      such patients. This report describes a surgical approach involving both maxillary
      subapical osteotomy and mandibular set-back surgery to correct the problem. This
      new surgical procedure not only produced optimum aesthetics but achieved the
      desired results in the shortest possible time.

PMID- 8149150
TI  - Adaptation of composite fillings to cavity walls in three different cavities.
AB  - Adaptation of eight kinds of resin restorations on Class V enamel cavity, cement
      enamel-junction (CEJ) cavity and root surface cavity were compared. Extracted
      human premolars were used as experimental specimens. Restored specimens were
      divided into two groups; short storage group of 2 week duration and long storage
      group of 6 month duration. The specimens were thermal cycled during storage.
      After that replicas of the vertical sections were made for examination by SEM and
      the gaps measured from photographs. The appearance and width of gaps between
      resin and cavity walls were characterised by the type of cavity and the filling
      materials. In Class V enamel cavity, gaps were observed on the cavity floor,
      whilst almost none was observed in other areas showing good adaptation. In the
      CEJ cavity, gaps appeared only at the cavity floor and gingival wall. In the root
      surface cavity, gaps were observed on all cavity walls with smaller widths on the
      occlusal wall and greater width on the cavity floor. Clearfil-F and Clearfil-F II
      showed fine adaptation on all cavities in general, especially on the dentinal
      cavity wall. Almost all the materials showed a tendency to form gaps which was
      found to increase with time. The difference in width, however, varied with the
      materials used.

PMID- 8149151
TI  - Shear bond strength of composite resin to unbleached and bleached human dentine.
AB  - The purpose of this study was to compare the shear bond strength of composite
      resin to unbleached and bleached human dentine when used in conjunction with new
      dentine bonding systems. One hundred extracted, caries free, permanent human
      molars were used in this study. An in vitro walking bleach model was developed to
      stimulate clinical conditions during bleaching. It was found that the mean shear
      bond strength of composite resin to bleached dentine attained was lower than that
      to unbleached dentine. The value of 6.7 MPa bond strength to bleached human
      dentine demonstrated by All-Bond dentine conditioner and adhesive (Technique 1B)
      was much higher than in previous reports.

PMID- 8149152
TI  - Aesthetic dental technique using a computer imaging system.
AB  - Patients are concerned about their appearance following an operation and would
      appreciate a preview of the final results. The key to treating a patient's
      anterior teeth is to first analyse his or her face, then develop a new tooth
      shape that is both functional and aesthetic. A computer imaging system can
      objectively portray the appearance which can be expected following an operation.
      Such a system, therefore, can be a very useful part of the armamentarium for
      analysis during the patient's pretreatment consultation.

PMID- 8149153
TI  - A consumer's guide to laparoscopic equipment for urology.
AB  - The ever increasing amount of laparoscopic instrumentation and the lack of any
      objective comparison make choosing the most appropriate equipment a difficult
      task for the urological neo-laparoscopist. All major manufacturers of
      laparoscopic equipment were invited to submit as much of their equipment as
      possible for inspection. A selection of ports, hand instruments, haemostatic
      devices and imaging systems was then tested in a laboratory and clinical setting.
      Costings are provided for evaluated ports, hand instruments and imaging systems.
      Vessels with a diameter greater than 7 mm, such as renal artery and vein, should
      be secured with a linear stapler-cutter. The optics of the Olympus OTV-S4, CLV-10
      light source, Olympus light cable and A5254A telescope are superior to the other
      imaging systems tested. Laparoscopic equipment is diverse in specification,
      performance and cost. Due consideration must be given to these factors when
      purchasing equipment to avoid disappointment and wastage of resources,
      particularly with regard to disposable instruments and imaging systems.

PMID- 8149154
TI  - Epididymo-orchitis due to brucellosis.
AB  - A diagnosis of epididymo-orchitis due to brucellosis was made in 13 patients
      between 1989 and 1991. Both testis and epididymis were involved in 8 patients, 3
      had bilateral epididymo-orchitis and 2 presented with orchitis alone. Patients
      were treated with a combination of 200 mg doxycycline and 600 mg rifampicin daily
      for 6 weeks and complete resolution was achieved in 10.

PMID- 8149155
TI  - Wolfram's (DIDMOAD) syndrome and its urological manifestation.
AB  - We report 2 patients with DIDMOAD syndrome (diabetes insipidus, diabetes
      mellitus, optic atrophy and neural deafness), with emphasis on the urological
      aspects and their management. Both patients underwent thorough radiological
      endoscopic and urodynamic evaluation, in addition to detailed evaluation of other
      systems involved. Each had the characteristic hyper-reflexive neurogenic bladder
      with sphincteric dyssynergia, which resulted in severe urinary tract dilation.
      One patient was diagnosed at this institution and managed conservatively with
      clean intermittent catheterisation and anticholinergic medication; the second
      patient was referred to us after several attempts at surgical correction. The
      presentation, details of the urological evaluation with special emphasis on the
      urodynamic findings, and the outcome of different means of management are
      discussed.

PMID- 8149156
TI  - Urethral atresia and the prune belly syndrome. Report of 6 cases.
AB  - An association between urethral atresia and the prune belly syndrome (PBS) has
      been recognised, but few reports discuss the outcome of treatment for these
      gravely ill patients. Of the 34 patients with prune belly syndrome evaluated at
      our institutions, 6 had urethral atresia (3 males and 3 females). Two of these
      patients died as neonates as a result of pulmonary insufficiency and 1 was
      stillborn. The common feature of the 3 surviving patients (2 males and 1 female)
      was the presence of a vesicocutaneous fistula. As neonates, 2 suffered from
      pulmonary insufficiency due to oligohydramnios. The mean length of follow-up for
      these 3 patients was 37 months (range 13-58). The urinary tract was decompressed
      in 2 patients by a formal vesicostomy performed early in life. The surviving girl
      has normal renal function following reconstructive surgery. Because both the
      bladder and urethra were absent in this patient, an ileocaecal bladder substitute
      and an appendiceal urethra were constructed. The 2 surviving boys both have renal
      insufficiency. One has received a renal transplant from a living relative and is
      doing well. In one of the boys, urethral atresia was initially managed by
      perineal urethrostomy and then by reconstructive surgery. Progressive catheter
      dilation was used on the other boy. Urethral atresia occurred in 18% of our
      patients with PBS; the incidence was equal in males and females. Survival
      correlated with the development of a spontaneous vesicocutaneous fistula. Two
      thirds of the survivors developed end-stage renal failure.

PMID- 8149157
TI  - Vesical endometriosis: value of laparoscopy.

PMID- 8149158
TI  - Xanthogranulomatous pyelonephritis and Wilms' tumour.

PMID- 8149159
TI  - Kaposi's sarcoma of the testis.

PMID- 8149160
TI  - Clear cell sarcoma of kidney in an adult.

PMID- 8149161
TI  - Carcinoma in situ in atrophic testis: biopsy based on abnormal ultrasound
      pattern.

PMID- 8149162
TI  - Malakoplakia and carcinoma of the prostate.

PMID- 8149163
TI  - Transitional cell carcinoma of the fossa navicularis.

PMID- 8149164
TI  - A simple technique to facilitate vesicourethral anastomosis following radical
      prostatectomy.

PMID- 8149165
TI  - Percutaneous puncture of non-deflating ureteric balloon dilatation catheter.

PMID- 8149166
TI  - An unusual complication of intracavernous self-injection of papaverine.

PMID- 8149167
TI  - Ureteric stent retrieval--"a better mousetrap".

PMID- 8149168
TI  - Continent bladder-sparing diversion for female urethral carcinoma.

PMID- 8149169
TI  - Extracorporeal shock wave lithotripsy for treatment of ureterolithiasis in
      patients with cystinuria.
AB  - Ten of 42 patients with cystinuria admitted for extracorporeal shock wave
      lithotripsy (ESWL) treatment had ureterolithiasis. Of these, 3 had bilateral
      stones, 2 had only 1 functioning kidney, and 2 had stones in both the kidney and
      ureter on the same side. Only 1 patient was on medical treatment at the time of
      referral. After initiation of medical treatment for cystinuria, 2 patients were
      discharged without further intervention, 1 was discharged after placement of a
      ureteric stent and 10 were treated with ESWL. After an average of 1.5 ESWL
      treatment sessions per ureter, 8 patients became stone-free and in the remaining
      2, ureteroscopy was required to complete the treatment. Problems associated with
      the ESWL treatment of cystine stones are discussed. It was concluded that ESWL is
      the treatment of choice for ureterolithiasis in patients with cystinuria because
      it is effective and is the least invasive procedure even in patients with
      cystinuria.

PMID- 8149170
TI  - Re: Urinary continence following radical retropubic prostatectomy. J. Ramon et
      al. Br. J. Urol., 71, 47-51, 1993.

PMID- 8149171
TI  - Helically ridged ureteric stent facilitates the passage of stone fragments in an
      experimental porcine model.
AB  - We have developed a ureteric stent with features designed to facilitate active
      expulsion of ureteric stone fragments. Its unique characteristics include a helix
      like ridge along a thin central core; the superior edge of the ridge is bevelled
      caudally and the inferior is concave. The ridge's outer edge is smooth and
      hydrophilic. As the stent is moved in relation to the ureteric wall (owing to
      respiratory motion and/or peristalsis), stone fragments will slip over the
      superior edge of the helical ridge. Once past this edge, they cannot migrate in a
      cephalad direction; they will pass down the helical trough or be ratcheted by the
      repetitive bevel and emerge through the ureteric orifice. To evaluate the
      effectiveness of the design it was compared with a conventional, smooth-surfaced
      double-pigtail stent in an ex vivo porcine model. A single artificial stone
      fragment (3 x 2 x 2 mm, 4 x 3 x 2 or 5.5 x 3 x 2 mm) was placed in the proximal
      ureter and the stent was moved up and down (56 studies with each type of stent).
      The helically ridged stent required a mean of 79 excursions (standard deviation
      60, range 8-291). In contrast, the conventional stent was unable to move any
      stone fragments--even after more than 1000 excursions.

PMID- 8149172
TI  - Endoscopic treatment of vesicoureteric reflux in transplanted kidneys.
AB  - Twenty-one patients underwent endoscopic subureteric injection of Polytef paste
      for the correction of secondary vesicoureteric reflux (VUR) in transplanted
      kidneys. Ureteroneocystotomy was performed in renal transplants using an
      extravesical technique in 19 patients and the Leadbetter-Politano technique in 2
      cases. Success was achieved in only 6 patients, including the 2 ureters
      reimplanted according to the Leadbetter-Politano technique. No significant
      complication relating to the technique was observed. Despite the low success rate
      (30%), endoscopic treatment of VUR in transplanted kidneys is justified as a
      first attempt in view of the morbidity of VUR and the difficulties of repeated
      surgical reimplantation in this population.

PMID- 8149173
TI  - Endoscopic transurostomy diathermy anastomotomy. A combined approach to uretero
      ileal stenoses.
AB  - Uretero-ileal stenosis is a recognised complication of ileal conduit urinary
      diversion. Two patients are described in whom a combination of fibreoptic
      conduitoscopy with standard endoscopic "biliary" sphincterotomy was used to treat
      anastomotic strictures. The technique of endoscopic transurostomy diathermy
      anastomotomy allowed the salvage of 3 renal units without the need for laparotomy
      or long-term indwelling ureteric stents.

PMID- 8149174
TI  - Prevalence and significance of urethral instability in women with detrusor
      instability.
AB  - The phenomenon of urethral instability has been poorly defined and its
      significance is disputed. The aim of this study was to investigate the prevalence
      and significance of urethral instability in a group of women with idiopathic
      detrusor instability. Urethral instability was defined as a spontaneous fall in
      maximum urethral pressure of one-third or more, in the absence of detrusor
      activity, over a 2-min period. Urethral instability occurred in 42% of patients
      with detrusor instability and was strongly associated with the sequence of
      relaxation of the urethra prior to unprovoked detrusor contraction. Women with
      detrusor instability and a stable urethra exhibited primary contraction of the
      detrusor. The symptom of stress incontinence was more common in women with
      urethral instability. Women with detrusor instability may be subdivided into 2
      groups on the basis of urethral instability, the presence of which suggests a
      primary dysfunction of the urethra. Such patients may derive more benefit from
      treatment with an alpha adrenoceptor agonist in addition to (or instead of)
      standard anticholinergic therapy.

PMID- 8149175
TI  - Association between urinary incontinence in women and a previous history of
      surgery.
AB  - In a cross-sectional study, 85% of 3114 women responded to a questionnaire on
      urinary incontinence and a history of abdominal, gynaecological and urological
      surgery. In 1987 the prevalence of urinary incontinence was 17%; 63% had
      undergone surgery, mainly gynaecological, and almost one-third of the respondents
      had had more than one operation. Bivariate and multivariate analysis showed
      stress urinary incontinence to be associated with previous exposure to surgery.

PMID- 8149176
TI  - Frequency-volume charts: comparison of frequency between elderly and adult
      patients.
AB  - Urinary frequency is a common complaint in the elderly and can be due to many
      different causes. To clarify the aetiology of frequency, patient-maintained
      frequency-volume charts were evaluated as a diagnostic tool. We studied 215
      patients who complained of frequency. They were divided into 2 groups based on
      age: 85 were over 65 years of age (elderly group) and 130 were less than 64 years
      old (adult group). Compared with the adults, elderly patients had a smaller
      urinary volume during waking hours and a larger volume during sleeping hours,
      with more frequent episodes of voiding and a smaller volume voided during the
      latter period. Analysis of the cause of frequency led to the patients being
      subdivided into 6 diagnostic categories. Among elderly patients, nocturnal
      polyuria (37%) and an unstable bladder (34%) were frequent causes. In adult
      patients an unstable bladder (28%) and polyuria due to excessive fluid intake
      (23%) were most common. As a result of our findings, 108 patients were advised
      not to be concerned about their micturition and/or restriction of fluid intake.
      Seventy-six patients (35%) required anticholinergic medication. Frequency-volume
      charts, together with a detailed medical history, provide useful information on
      the diagnosis and treatment of frequency.

PMID- 8149177
TI  - Desmopressin in elderly women with increased nocturnal diuresis. A short-term
      study.
AB  - We report the changes in the pattern of diuresis in 20 women (average age 71
      years) with increased nocturnal diuresis who were treated with 20 micrograms
      desmopressin (Minirin). Before treatment, antidiuretic hormone levels were
      measured every 4 h over a 24-h period and 75% of the levels were found to be
      beneath the lowest detectable limit (< 0.4 pmol/l). Nocturnal diuresis decreased
      by 355 +/- 208 ml and in 8 cases the decrease exceeded 400 ml. Diurnal diuresis,
      on the other hand, increased by 226 +/- 331 ml. Side effects were mild and
      occurred in only 2 women.

PMID- 8149178
TI  - Activity patterns of pubococcygeal muscles in nulliparous continent women.
AB  - Simultaneous electromyographic (EMG) recordings from the left and right
      pubococcygeal muscles were obtained in 10 continent nulliparous women (aged 22-32
      years) via wire electrodes inserted percutaneously. During relaxation, sustained
      motor unit firing was obtained in 14 and no EMG activity in 4 of the 20 recorded
      muscle sites. During voluntary squeeze, stopping urine in midstream and coughing
      there was always bilateral recruitment of motor units that was gradual in the
      recording sites with ongoing EMG activity and brisk in the sites without EMG
      activity; the 2 different patterns of activity were called "tonic" and "phasic"
      respectively. Voluntary squeeze led to activation of motor units sustained for 26
      to 647 s (median 193.9) with the bladder empty and 25 to 600 s (median 198.4)
      with a full bladder. A marked decrease in ongoing tonic motor unit activity was
      seen during the attempt to urinate. Bladder filling caused an increase in tonic
      activity in 7 females bilaterally and in 1 unilaterally, whereas there was no
      change in 3 women. During the Valsalva manoeuvre, simultaneous motor unit
      recruitment was seen in all subjects bilaterally with the bladder empty and in
      all but one with the bladder full: in the latter case the motor unit recruitment
      with an empty bladder changed into simultaneous bilateral inhibition of firing of
      motor units with a full bladder (both in the supine and erect position); this
      pattern changed to bilateral recruitment of motor units again after bladder
      emptying. It is important to be familiar with the normal patterns of activity of
      the pubococcygeal muscles in continent nulliparous women since the denervation
      injury caused by childbirth might not only weaken these muscles but also
      influence their behaviour.

PMID- 8149179
TI  - The role of the Mathieu repair as a salvage procedure.
AB  - Conceived as a primary single-stage procedure for coronal and subcoronal
      hypospadias, the Mathieu repair has not been previously described as a salvage
      operation in situations where other forms of hypospadias surgery have failed to
      give an adequate functional or cosmetic result. We describe the use of the
      operation as a planned salvage procedure.

PMID- 8149180
TI  - Urinary retention after renal and ureteric surgery.
AB  - A retrospective study was carried out on 200 patients who underwent surgery
      between January 1989 and September 1991. The aim was to investigate the
      development of urinary retention following renal and ureteric surgery. The
      incidence of urinary retention was 55% for patients in the renal group and 26%
      for those in the ureteric group. In a control group of 100 patients undergoing
      cholecystectomy the incidence was 5%. The results showed that bladder function
      was inhibited greatly after renal surgery. Catheterisation in the pre-operative
      period may help to prevent post-operative urinary retention.

PMID- 8149181
TI  - Autoaugmentation gastrocystoplasty in a sheep model.
AB  - Ten lambs had their bladders augmented with de-epithelialised stomach muscle
      added to an intact urothelium. They were assessed functionally and histologically
      up to 2 months post-operatively. The urothelium remained viable with minimal
      inflammation and a neo-bladder with good volume was formed.

PMID- 8149182
TI  - Genitourinary malakoplakia.
AB  - Between 1973 and 1991, 13 patients with malakoplakia (MKP) have been diagnosed
      and treated. The lesions involved all sites in the genitourinary tract; 2
      patients had multiple and 11 had single lesions. Treatment was based on 2
      criteria: (a) pharmacological treatment with trimethoprim-sulphamethoxazole
      and/or ascorbic acid and/or bethanechol chloride; (b) excision of the MKP lesion
      either endoscopically or by open surgery. Two patients died (1 from multiple MKP
      and the other from a myocardial infarct); the remainder did well. The pathogenic,
      diagnostic and therapeutic aspects of the disease are discussed.

PMID- 8149183
TI  - Urinary levels of tumour associated antigens (CA 19-9, TPA and CEA) in patients
      with neoplastic and non-neoplastic urothelial abnormalities.
AB  - The urinary excretion of carbohydrate antigen 19-9 (CA 19-9), tissue polypeptide
      antigen (TPA) and carcinoembryonic antigen (CEA) was evaluated in 264 patients
      with bladder cancer. Cut-off levels were established using a pool of healthy
      blood donors. The combined determination of CA 19-9 and TPA had a sensitivity of
      74% in pTa and 83% in pT1 tumours, and 62% in grade 1, well differentiated
      tumours. Absence of disease at follow-up was related to a significant decrease in
      CA 19-9 and TPA in 129 patients with superficial (pTa or pT1) bladder carcinoma,
      followed up for at least 3 years. Recurrences, defined as new tumours at the same
      site or elsewhere in the bladder, were associated with an increase in the mean
      values but this was not statistically significant. A poor prognosis was indicated
      in patients with infiltrating tumours and the following pre-operative levels: TPA
      > 1500 u/l or CA 19-9 > 300 u/ml or CEA > 50 ng/ml.

PMID- 8149184
TI  - Hyperthermic intravesical peplomycin perfusion treatment for bladder cancer.
AB  - Thirty-three patients with malignant bladder tumours were treated by hyperthermic
      intravesical perfusion. The study group included 25 patients with superficial T1
      bladder tumours, 4 with T2 tumours and 4 with T3 tumours. Physiological saline
      solution containing 40 micrograms/ml peplomycin with/without 2% ethanol was used
      as a perfusate. Perfusion was carried out for 2 h 3 times per week and this
      regimen was repeated every other week, totalling 6 sessions in 3 weeks. Three
      patients achieved a complete response (CR), 5 a partial response (PR) (more than
      50% tumour reduction), 8 a minimal response (MR) (25-50% tumour reduction) and
      the remaining 17 patients showed no response (NC). Complete, partial and minimal
      responses were obtained only in patients with T1 tumours. The NC patients
      included 4 with T2 and 4 with T3 lesions. Profuse haematuria from invasive tumour
      was markedly reduced after treatment. A major side effect was irritation of the
      bladder and urethra. Our results indicate that hyperthermic perfusion with
      ethanol and peplomycin is clinically safe, is accompanied by very little pain and
      may be useful for the management of superficial bladder tumours in elderly
      patients.

PMID- 8149185
TI  - Haemodynamic effects of transurethral prostatectomy.
AB  - Thoracic bio-impedance cardiography was used to study the haemodynamic changes in
      28 patients undergoing transurethral prostatectomy (TURP) under either general or
      spinal anaesthesia. Cardiac output and mean arterial pressure fell with induction
      of general anaesthesia, whilst mean arterial pressure and systemic vascular
      resistance fell with induction of spinal anaesthesia. The transthoracic fluid
      index fell during resection under general anaesthesia, but no significant
      haemodynamic changes were seen during resection under either anaesthetic. This
      study suggests that resection has no specific adverse haemodynamic consequences.
      Spinal anaesthesia may produce less haemodynamic disturbance than general
      anaesthesia in patients undergoing TURP and formal comparison of the 2 techniques
      seems necessary.

PMID- 8149186
TI  - Absorption of irrigating fluid and height of fluid bag during transurethral
      resection of the prostate.
AB  - The purpose of this study was to examine the relationship between the static
      pressure and the absorption of irrigating fluid during transurethral resection of
      the prostate. We measured the absorption by the ethanol method in 550 operations
      during which the fluid bags were placed randomly at distances of 60-65, 70-75, 80
      85 or 90-100 cm above the operating table. There was no difference in the volume
      of irrigant absorbed at different bag heights or any association between fluid
      height and absorption when different ranges of fluid absorption were analyzed.
      This suggests that irrigant absorption cannot be prevented by placing the fluid
      bags at a certain height within the range of 60 to 100 cm above the operating
      table.

PMID- 8149187
TI  - Distinction between focally accelerated bone formation and osteomalacia in
      carcinoma of prostate metastasised to bone.
AB  - We studied the histological indices of skeletal turnover in 40 patients with
      carcinoma of the prostate and skeletal metastases in order to determine the
      prevalence of osteomalacia. In 20 patients biopsied through uninvolved bone, the
      histological indices of bone turnover were normal. In particular, osteoid seam
      width and bone formation rates were consistently normal, indicating the absence
      of osteomalacia. In biopsies from tumour-laden bone, hyperosteoidosis was
      present, usually associated with increased amounts of woven collagen and
      consistently associated with high rates of bone formation and mineralisation. It
      was concluded that hyperosteoidosis in prostatic cancer is rarely due to
      osteomalacia.

PMID- 8149188
TI  - Alcohol, AIDS and immunity.
AB  - In order to understand the potential impact of alcohol consumption on the course
      of the HIV/AIDS pandemic we examine at least 3 very different debates. In an
      attempt to summarise these debates we assess the impact of alcohol consumption on
      numerous aspects of HIV infection, including the relationship between alcohol use
      and likelihood of engagement in 'unsafe' sexual behaviour; the impact of alcohol
      on immune function and its importance as a co-factor for AIDS-related illness. We
      argue that, contrary to popular belief, the consumption of alcohol does not
      appear to make individuals more likely to engage in unsafe sex. Furthermore,
      while alcohol has clearly been proven to effect immune function in vivo and in
      vitro there is no clear evidence that it plays any part in individuals'
      susceptibility to HIV infection or has any effect on disease progression among
      persons with HIV infection. Clearly some of this research is in its infancy and
      such conclusions should be treated with caution.

PMID- 8149189
TI  - Liver damage: mechanisms and management.
AB  - Despite recent advances in our knowledge of the mechanisms of alcohol-induced
      liver damage, abstinence from alcohol and supportive measures remain the
      mainstays of management for the majority of patients. Progress has been made in
      our understanding of ethanol metabolism, the role of acetaldehyde, and both
      genetic and environmental factors responsible for the variation in individual
      susceptibility to alcoholic liver disease. Evidence for the involvement of the
      immune system and the effects of alcohol on hepatic fibrosis are also reviewed.
      Recent therapeutic trials of corticosteroids in acute alcoholic hepatitis have
      confirmed their benefit in patients who have a high risk of mortality. For
      patients with end-stage cirrhosis, orthotopic liver transplantation is now an
      accepted therapy in selected patients who have a good prognosis for future
      abstinence.

PMID- 8149190
TI  - Ethanol induced cardiovascular disease.
AB  - Although the beneficial effects of mild or moderate ethanol consumption have been
      implied with respect to coronary artery disease, excessive ethanol consumption
      can result in alcoholic heart muscle disease (AHMD). The latter is characterized
      by features consistent with dilated cardiomyopathy with concomitant ventricular
      dysfunction and histopathological abnormalities. By definition, no other cause
      for the abnormalities in AHMD is demonstrated, other than excessive alcohol
      consumption. The metabolic basis of AHMD is probably multi-factorial, and the
      alterations of myocardial biochemistry are contributing factors for the
      precipitation and progression of the disease. The latter may reverse with
      abstention. Evidence is provided to support the contention that the abnormalities
      include central defects in protein metabolism, which perhaps are engendered by
      free radicals and/or the formation of acetaldehyde adducts. The latter may
      initiate the formation of auto-antibodies, therefore providing an auto-immune
      basis for AHMD in chronic alcohol misuse. Evidence is also provided to show that
      acetaldehyde is a potent perturbant of protein synthesis, and reduces the
      formation of new contractile proteins.

PMID- 8149191
TI  - Alcohol misuse as challenge to medical education: a belated remedy.
AB  - Substance misuse contributes directly or indirectly to each of the 5 key targets
      outlined in the Health of the Nation strategy: coronary heart disease and stroke,
      cancers, mental illness, HIV/AIDS and accidents. More specifically, the risk
      factor targets include a 30% reduction in the prevalence of cigarette smoking to
      no more than 20% in both men and women by the year 2000; a 30% reduction in the
      proportion of men drinking more than 21 units of alcohol per week and women
      drinking more than 14 units per week to 18% and 7% respectively, and reduction in
      the percentage of drug misusers sharing equipment to no more than 5% in the year
      2000. The Tomlinson report repeatedly underscores the problems of drug misuse,
      alcohol problems and mental illness in Inner London. Both these recent reports
      admit to a 'lack of trained professionals' (p17) and to 'ensuring that
      professionals ... are adequately and appropriately educated' (p97). Furthermore,
      Health of the Nation declares that 'Professional bodies in health and social work
      will continue to design training to promote the early identification of alcohol
      misuse, and appropriate referral skills' (p16).

PMID- 8149192
TI  - Prevention policies.
AB  - Alcohol is a special commodity because of its dependence producing properties and
      the extent and severity of problems associated with its use, many of which are
      preventable. The elements of a comprehensive preventive policy include: controls
      to raise the price of alcohol; controls on the availability of alcohol,
      particularly minimum age limits for the purchase of alcohol and limits to the
      hours and days of sale of alcohol and numbers of outlets; controls on the use of
      alcohol, particularly restricting drinking and driving; product safety standards,
      particularly information on the alcohol content of beverages, controls on
      marketing, particularly restrictions on advertising and sponsorship and;
      education and information programmes, including those based at a community level
      to promote support for prevention policies and those based in schools and primary
      health care.

PMID- 8149193
TI  - Genetics of alcohol misuse.
AB  - Family, twin, and adoption studies demonstrate the genetic contribution to
      alcoholism but also confirm an important environmental component. The current
      rapid developments in genetics are providing candidate genes that can be assessed
      for a role in alcoholism, and a reported association with the DRD2 receptor gene
      is still being examined. Alcoholism is a complex behaviour which may be more
      amenable to genetic studies when dissected into its constituent parts. It is
      probable that multiple genes contribute to the genetic vulnerability to
      alcoholism and, hopefully, the effect of some will be of sufficient size so that
      they can be identified. Identification of these vulnerability factors will allow
      targeting of preventative efforts but before genetic tests are used clinically
      the full ethical implications will need to be considered carefully.

PMID- 8149194
TI  - A conditioning approach to the analysis and treatment of drinking problems.
AB  - Drinking problems are a major public health concern and a significant part of
      this concern arises because drinking habits are very difficult to change once
      established; although many patients can detoxify successfully there is a high
      rate of relapse. This chapter describes the analysis and treatment of drinking
      problems using a behavioural approach based on the concepts and methods of
      classical conditioning. Recent evidence shows that alcoholic patients show a
      variety of physiological and subjective responses to the presentation of
      alcoholic drink cues and these responses may play a part in the regulation of
      drinking behaviour. The implication is that cue-exposure treatments ought to
      reduce drinking. In cue-exposure, responses to drink cues are extinguished by
      repeated presentation of the cue without allowing subsequent consumption of
      alcohol. The empirical evidence for the effectiveness of such treatments is
      described and the current status of the approach to the analysis and treatment of
      drinking problems will be summarised.

PMID- 8149195
TI  - Alcohol problems in the general hospital.
AB  - The likelihood of a man being admitted to a general hospital for liver disease,
      myocardial infarction, other cardiovascular disease, upper gastrointestinal
      disease and acute trauma increases progressively as admitted alcohol intake
      increases, commencing at an admitted consumption of 30/g per day. Heavy drinkers
      are also more likely than light drinkers to be admitted for respiratory
      disorders, presumably because of the connection with smoking. In addition to
      these and other medical conditions linked to alcohol use, there are admissions
      directly related to alcohol dependence and its complications such as fits, or
      delirium. Trends in general hospital discharges for alcohol dependence, psychosis
      and misuse for the 1980's have been examined in Scotland and found to have
      increased, in a period when discharges for alcohol disorders from psychiatric
      hospitals have decreased (Figs 1-3). Changes in diagnostic practices are unlikely
      to account for such a large change, but a shift from psychiatric to general
      hospital may have contributed.

PMID- 8149196
TI  - Alcohol: strengthening the primary care response.

PMID- 8149197
TI  - Alcohol policy--evaluating the options.
AB  - All policy interventions have costs and benefits and the 'harm' created by the
      use of alcohol can only be mitigated at a cost. The purpose of economic analysis
      is to measure these costs and benefits in an explicit way and to use these
      results to inform policy. Policy makers like to use estimates of the social costs
      of alcohol use but such data are of little use in identifying which interventions
      reduce harm at least cost: knowing alcohol use costs in local currencies $6
      million in Australia, $5.8 billion in the USA, $5.7 billion in Canada and $2
      billion in the UK may fuel political debate but does not identify the
      intervention where investment produces the greatest increase in benefit at least
      cost. Integrated policies to raise taxes in relation to price and income changes
      have significant impacts on alcohol consumption and, if complemented with
      advertising controls and limits on availability have even larger effects. The
      quantity and quality of economic evaluations of health care interventions is
      inadequate. What little evaluation that has been undertaken indicates that low
      cost minimal interventions may be cost effective for the wider population of
      problem drinkers. Other more intensive interventions are likely to be cost
      effective only if well targeted on appropriate client groups. There are many
      effective ways of reducing alcohol consumption. The industry will lose and oppose
      change but improvements in health and other aspects of life (eg civil order) will
      be significant.

PMID- 8149198
TI  - Alcohol misuse and the predisposing environment.
AB  - In recent years, the aetiology of alcohol misuse has come to be conceptualised in
      terms of risk factor models. Risk can emanate from a number of sources ranging
      from the genetic to the sociostructural. This chapter reviews the major
      environmental risk factors under two broad headings--those that affect the
      availability of the agent and those that affect the vulnerability of the host.
      The former include a variety of economic, social and physical factors such as
      price, advertising and licensing laws. The latter include broad socioeconomic and
      sociocultural factors, as well as interpersonal influences such as family, peers,
      employment and stress. Practitioners (as distinct from policy-makers) concerned
      with prevention and treatment of alcohol misuse can most effectively intervene at
      the interpersonal level, and the paper concludes with a discussion of the
      implications for clinical practice of the research reviewed in this domain.

PMID- 8149199
TI  - Alcohol: the drug.
AB  - The purpose of this chapter is to bring together some of the recent research that
      has significantly increased our knowledge of the mechanisms underlying the
      actions of alcohol in the body, including absorption and metabolism. One
      particular field of growth is that of the actions of alcohol in the brain. In the
      past few years there have been a number of important advances in our
      understanding of the mechanisms by which alcohol produces sedation, intoxication
      and pleasure as well as those processes which contribute to its addictive
      properties. Progress has also been made in unravelling the mechanisms of
      tolerance and physical withdrawal and these studies have also thrown light on the
      basis of the neurotoxic effects of alcohol. Similarly in the periphery new ideas
      about the toxic tissue damaging properties of alcohol have been developed.

PMID- 8149200
TI  - What happens over the long-term?
AB  - What happens over the long-term course of alcoholism focuses our view on a number
      of issues found throughout the literature of alcoholism studies, placing them in
      a quite different perspective. When trying to encompass the effects of what may
      be a chronic condition, lasting for decades, the importance of short-term
      prognoses and treatment results falls back and gives centre stage to the overall
      pattern of events. Treatment episodes recur and become an accumulated treatment
      experience, a voluntary consumption pattern of treatment services. The
      spontaneous recoveries that take place in the community and the undiagnosed cases
      of alcoholism that do not reach for medical intervention take on a special
      significance in charting the general course. The backdrop of maturing and ageing
      processes interacts with a life course of events in determining the direction of
      the play.

PMID- 8149201
TI  - Alcohol and bone.
AB  - It is well known that the prolonged use of excess alcohol causes a multiplicity
      of abnormal clinical, biochemical and electrophysiological changes that are
      associated with diseases of the liver, neuromuscular system, heart and brain. It
      is less well appreciated that the long-term use of excess alcohol also effect
      bone and may play an important role in the causation of extensive bone loss, and
      osteoporosis.

PMID- 8149202
TI  - Alcohol and accidents.
AB  - The association between alcohol use and accidental injury or death has been
      acknowledged for a long time. Alcohol is thought to contribute to 50,000 deaths
      per year and up to 500,000 hospital admissions annually in the UK. Thus, up to
      40% of all hospitalisation relates directly or indirectly to alcohol.

PMID- 8149203
TI  - Aetiology of alcoholic brain damage: alcoholic neurotoxicity or thiamine
      malnutrition?
AB  - The clinical presentation of brain damaged alcoholics is heterogenous and
      includes minimal cognitive impairment, amnesia and dementia. Whichever
      neurobiological technique is used, eg neuropathology, structural and functional
      neuroimaging, the clinico-pathological evidence suggests that thiamine
      malnutrition, affecting the diencephalon, can account for all clinical forms.
      Alcohol neurotoxicity can cause neuronal damage in cerebral cortex and can
      contribute to cognitive impairment but there is little direct evidence to support
      the need for a distinct clinical category of alcoholic dementia. Most organic
      brain syndromes in alcoholics therefore can be considered as variants of the
      Wernicke-Korsakoff syndrome and rigorous attention should be paid to the
      nutritional status of all alcoholics.

PMID- 8149204
TI  - Clinical variability in Becker muscular dystrophy. Genetic, biochemical and
      immunohistochemical correlates.
AB  - We have investigated 59 Becker muscular dystrophy patients, representing 56
      independent mutations, to test the hypothesis of predictability of muscle
      dystrophin expression and clinical phenotype based on location of dystrophin gene
      mutations. Partial intragenic deletions and duplications account for 82% of the
      independent mutations, of which 76.7% were deletions and 5.3% duplications.
      Mutations in which boundaries could be defined, were of in-frame type (35 out of
      37, 94.6%, with two exceptions. Eighty-two percent of mutations were located at
      the distal part of the rod domain (exons 45-60), 9% at domain I (promoter through
      exon 9) and 9% at proximal and central parts of domain II. Domain I deleted
      patients tended to have a worse clinical phenotype, with earlier presentation,
      faster progression rate and lower dystrophin expression, while distal rod domain
      deleted patients showed a more classic Becker muscular dystrophy phenotype.
      Between these two groups, only the differences in the immunohistochemical
      patterns of dystrophin expression and disease progression rate were statistically
      significant. Partial clinical and biochemical heterogeneity was observed in the
      distal domain II patient group, due to the presence of few patients covering the
      extremities of clinical severity. Two asymptomatic patients had deletions located
      in the central (exons 41-44) and distal parts (exons 50-53) of the rod domain.
      Severe myalgia and cramps were often reported as early onset symptoms (18 out of
      59): no correlation was found between this symptomatology and the location of the
      mutation. Relative levels of muscle dystrophin correlated with
      immunohistochemical patterns of subsarcolemma staining. Dystrophin levels (as
      estimated by 30 kDa antibody immuno-reactivity) correlated with age of reaching a
      moderate degree of muscle involvement as well as with delay in reaching that
      stage, a parameter of disease progression rate. Our data confirm that different
      Becker muscular dystrophy gene in-frame mutations have different effects on
      dystrophin expression and clinical severity, indicating several functional roles
      of the dystrophin domains.

PMID- 8149205
TI  - The disconnection syndrome. Basic findings reaffirmed.
AB  - Recent challenges to the traditional view of the disconnection syndrome have been
      based primarily on evidence of information shared between the hemispheres in
      commissurotomy patients L.B. and N.G. of the West Coast series. In order to
      evaluate the generality of these claims, patients J.W., V.P. and D.R. were tested
      using a series of experiments which replicated and extended some of the
      experiments carried out in the West Coast series. Using comparisons of numerical
      identity and value as the model tasks, we found no indication that the separated
      hemispheres of J.W. or D.R. could share information on any of the tasks they
      performed. V.P., who has spared callosal fibres and has shown highly specific
      transfer in previous investigations, performed above chance (60%) in one out of
      three between field conditions. Together the data fail to support the claims that
      split-brain patients show evidence of unified cognitive functioning particularly
      for more abstract, nonperceptual tasks. The data are consistent with the
      traditional view of the corpus callosum as the primary interhemispheric pathway
      by which sensory and high-level cognitive integration is achieved.

PMID- 8149206
TI  - Cortical tongue area studied by chronically implanted subdural electrodes--with
      special reference to parietal motor and frontal sensory responses.
AB  - Motor and sensory cortical tongue representations were examined in 40 patients
      with intractable seizures who underwent chronic subdural electrode grid
      implantation. Tongue responses were observed in a wide area 4.5 cm anterior and 3
      cm posterior to the central sulcus. The distribution of the responses was not
      influenced by whether the responses were unilateral or bilateral. In patients
      with fronto-parietal lesions, the tongue motor area was located significantly
      more superior to the Sylvian fissure and more anterior to the central sulcus than
      was the tongue motor area of patients without organic lesion. Both motor and
      sensory responses were found outside of the classic precentral or postcentral
      area on the lateral surface of the cortex. Motor responses ('parietal motor
      responses') could occur posterior to the central sulcus and, rarely, sensory
      responses ('frontal sensory responses') were identified anterior to the central
      sulcus. These paradoxical parietal motor and frontal sensory responses were seen
      in 17 out of 40 (42.5%) patients. Nine of these 17 patients had no organic brain
      lesion on MRI. Clinical factors, such as patient's age, duration of seizures and
      cognitive functions (IQ, word fluency score), did not influence the frequency of
      the paradoxical responses. However, patients with brain lesions showed a tendency
      to have associated paradoxical responses (P < 0.05). In conclusion, paradoxical
      responses are not uncommon in epilepsy patients, particularly in those with
      organic lesions. The physiological and clinical implications of the paradoxical
      responses are discussed.

PMID- 8149207
TI  - A new appraisal of abnormalities of the odontoid process associated with atlanto
      axial subluxation and neurological disability.
AB  - It is well known that abnormalities of the odontoid process may be associated
      with subluxation and neuraxial compression. Modern computerized imaging is
      demonstrating that existing classifications are in need of revision since they no
      longer reflect current views on development, nor do they adequately explain the
      patterns of abnormality commonly encountered in clinical practice. This study is
      a description of 62 varied clinical cases examined by high definition
      computerized myelography or MRI in flexion and extension, some before and after
      stabilization procedures. From these descriptions, and a review of the old and
      more recent literature concerning phylogenesis and ontogenesis of the odontoid,
      the following conclusions were drawn. The dens within the atlas ring is not
      morphologically a centrum of the first cervical vertebra, but a projection
      arising from it. In os odontoideum the dens forms normally, but ossifies
      abnormally because of abnormal motion; it is a result rather than the cause of
      instability. Hypoplasia of the dens is usually incorrectly diagnosed. When
      present it is associated with atlanto-occipital assimilation, fusion of the
      second and third, or more, cervical vertebrae, loss or reduction in axial
      rotation of the head, basilar invagination and hindbrain deformity of Chiari
      type. Therefore it is part of a regional anomaly involving hypoplasia of the
      derivatives of the occipital and upper cervical somites. Recognition of these
      aspects simplifies both diagnosis and the formulation of therapeutic strategies
      for different types of clinical presentation.

PMID- 8149208
TI  - A psychophysical study of the mechanisms of sensory recovery following nerve
      injury in humans.
AB  - Twenty-four subjects were studied before and up to 1 year after surgery that
      produced injury to a major sensory branch of the trigeminal nerve. We employed a
      battery of 11 psychophysical tests, in which the neural mechanisms underlying
      performance are understood, to study the basis of recovery following nerve
      injury. Immediately after nerve injury, sensation was profoundly impaired in all
      subjects. In the following weeks and months, the recovery of performance
      proceeded in an orderly fashion. Although the rates of recovery varied between
      subjects, the order of recovery between tasks did not. The recovery rates fell
      into three distinct categories. Recovery in one task, brush-stroke directional
      discrimination, was most rapid. Two weeks after nerve injury, 52% of subjects
      could discriminate brush-stroke direction; by 3 months only one subject could not
      perform this task. The second category comprised recovery rates for pain
      thresholds for noxious heat, cold and mechanical stimuli, and to preinjury
      performance in tasks assessing touch and vibration detection, two-point
      discrimination, cooling detection and subjective magnitude estimation of
      mechanical force. The third, slowest group included recovery rates for warming
      detection and grating orientation discrimination. Early recovery to preinjury
      performance levels in the brush-stroke direction and one-point versus two-point
      discrimination tasks was correlated with later recovery to near normal
      performance in the grating orientation task. The grating orientation task was
      unique in providing a measure that corresponded consistently with the subjects'
      reports of sensory deficits. Our psychophysical findings are consistent with
      neurophysiological data showing that the major primary afferent fibre classes
      reinnervate the skin at a similar rate. A hypothesis that accounts for the
      psychophysical findings in this study is that differences in recovery rates
      between tasks is determined largely by their relative dependencies on functional
      innervation density. Alternative hypotheses are considered.

PMID- 8149209
TI  - Comparison of oculomotor findings in the progressive ataxia syndromes.
AB  - In this study we compare the results of quantitative oculomotor function testing
      in patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA)
      and cerebello-olivary atrophy (CA). Common features in all three syndromes
      included gaze-evoked nystagmus, saccade dysmetria and prolonged saccade reaction
      times. Patients with FA showed a characteristic combination of frequent saccadic
      intrusions, especially ocular flutter, relatively preserved optokinetic nystagmus
      (OKN) and smooth pursuit, and impaired vestibulo-ocular reflex (VOR) responses.
      In patients with CA saccadic intrusions were infrequent, OKN and smooth pursuit
      were severely impaired and VOR gain was normal or increased. Results in OPCA were
      more variable. When present, slowing of saccades or the combined loss of pursuit
      and vestibular function were characteristic for OPCA. The ability to suppress the
      VOR with a head fixed target was relatively preserved in FA, normal to moderately
      impaired in OPCA and always severely impaired in CA. We conclude that oculomotor
      testing is useful in the differential diagnosis of the progressive ataxia
      syndromes.

PMID- 8149210
TI  - Properties of cutaneous afferents during recovery from Guillain-Barre syndrome.
AB  - The technique of percutaneous microneurography was used to record from 60
      mechanosensitive cutaneous afferents in patients (n = 5) who were recovering from
      acute Guillain-Barre syndrome (GBS) and who displayed residual sensory deficits
      in the hands. Recordings were obtained from median and ulnar nerves, between 1
      and 31 months following plasma exchange therapy. The behaviour of all four types
      of cutaneous afferents known to innervate the glabrous skin of the normal hand
      (rapidly adapting types RA and PC and slowly adapting types SAI and SAII) was
      studied in response to mechanical skin stimulation. Some of the units could not
      be fully classified. Additionally, intradermal electrical stimulation was used to
      study conduction velocity and absolute refractory period. Abnormal response
      behaviour was encountered in RA, PC and slowly adapting afferents. The
      abnormalities consisted of a generation of only a single action potential to
      above threshold stimuli (RA), inability to follow high frequency vibration (PC)
      and, in slowly adapting afferents, reduced discharge rates during sustained skin
      indentations or cessation of discharge during indentation. Abnormally responding
      units were more frequently found in patients with marked, than in those with
      mild, clinical sensory symptoms. In the former, half of all units in each patient
      responded abnormally (12 out of 23 in total). In patients with mild symptoms,
      most units (33 out of 37) were normal in response behaviour as well as in other
      measures made: threshold to mechanical stimuli, static discharge rate, receptive
      field size, conduction velocity, absolute refractory period. Spontaneous activity
      of unknown origin was also encountered in some patients. The activity consisted
      of highly regular discharge bursts or relatively regular unitary discharges. The
      data indicate that the encoding capabilities of all types of cutaneous afferents
      (RA, PC, SAI and SAII) may be affected in GBS, contributing to the sensory
      deficits of the disease. The abnormal encoding most likely reflects a limited
      ability of the axons to conduct trains of action potentials.

PMID- 8149211
TI  - The triple cold syndrome. Cold hyperalgesia, cold hypoaesthesia and cold skin in
      peripheral nerve disease.
AB  - A syndrome of cold hyperalgesia associated with cold hypoaesthesia is described
      in 28 patients with peripheral polyneuropathy or mononeuropathy of various
      aetiologies. A mechanism of sensory disinhibition, where diminished cold-specific
      A delta input releases cold pain input carried by C nociceptors, is proposed to
      explain the hyperalgesia. In most patients, the symptomatic skin is abnormally
      cold. This is a likely consequence of vasospasm, due to sympathetic denervation
      supersensitivity, caused by dropout of sympathetic efferents as part of the small
      caliber nerve fibre insult. The term 'triple cold syndrome' is coined to describe
      this specific pathophysiological condition. Descriptively it is a mirror image of
      erythralgia, as described by Sir Thomas Lewis (1936) and updated by one of the
      present authors, a human condition also centred around anomalous primary
      nociceptor input, in which there is heat hyperalgesia and hot symptomatic skin
      due to C nociceptor sensitization and vasodilatation from antidromic discharge.
      Thus, like the latter condition, the triple cold syndrome emerges as an
      independent clinical entity with definable abnormal mechanisms which should be
      retrieved out of the all-embracing, descriptive, diagnostic category 'reflex
      sympathetic dystrophy--causalgia'.

PMID- 8149212
TI  - Electromyographic features of levator palpebrae superioris and orbicularis oculi
      muscles in blepharospasm.
AB  - Electromyographic (EMG) recording was performed synchronously from the levator
      palpebrae superioris (LP) and the orbicularis oculi (OO) muscles in 28 patients
      referred to us for treatment of blepharospasm with botulinum A toxin. At the time
      of this study, 19 patients were under the treatment with botulinum, four started
      treatment shortly after the EMG recording and five patients had not yet been
      treated. Based on the EMG patterns, we were able to classify five major groups of
      abnormalities. Group 1 (blepharospasm): consisted of 10 patients with dystonic
      discharges limited to OO, normal LP tonic activity, intact reciprocal inhibition
      between LP and OO and dense bursts of action potentials with high amplitude
      preceding the return of LP tonic activity, i.e. 'postinhibition potentiation' of
      LP, brought about by a brief contraction of OO. Group 2 (combined dystonic
      activities of LP and OO): seven patients belonged to this group. The EMG
      recording revealed alternating tremulous discharges in both LP and OO muscles,
      and short intervals of co-contractions due to moderately disturbed reciprocal
      inhibition. Group 3 (combination of blepharospasm, LP motor impersistence): the
      EMG patterns, observed in three patients, were characterized by a gradual
      cessation of LP activity, followed by a brief contraction of OO, which
      facilitated the return of LP activity, resulting in opening of the eyes. The EMG
      recordings, thus, revealed the crucial, beneficial role of postinhibition
      potentiation as a compensatory mechanism in this type of eyelid movement
      disorder. The EMG patterns were also characterized by short or prolonged periods
      of dystonic discharges limited to the OO muscles. Group 4 (combination of
      blepharospasm, involuntary LP inhibition): this group consisted of four patients.
      In addition to episodes of dystonic activities of OO, the EMG also showed some
      periods of involuntary inhibition of LP without any concomitant activities of OO.
      Two patients also exhibited a failure of inhibition of OO muscle activity,
      following the voluntary contraction of this muscle. The postinhibition
      potentiation was often not observed. Group 5 (involuntary LP inhibition):
      consisted of four patients with EMG patterns of involuntary inhibition of LP
      activity, without any dystonic discharges in OO. The postinhibition potentiation
      was not observed in this group. The response to the treatment with botulinum
      toxin was good in the first group and gradually worsened towards the fifth group.
      Application of botulinum into multiple sites of OO, especially its pretarsal
      portion, resulted in better response to the treatment in the second and fourth
      groups.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8149213
TI  - Rapid wrist movements in patients with essential tremor. The critical role of the
      second agonist burst.
AB  - Ballistic wrist flexion movements towards 15, 30 and 60 degrees visual targets
      were studied in a group of 17 patients with hereditary essential tremor. Compared
      with age-matched normal subjects (n = 16), there were three main kinematic
      differences: patients overshot the target a little more; the kinematic profile of
      their movements was more 'asymmetric' due to higher peak decelerations; and their
      movements initiated tremor. Ballistic movements performed by patients with
      essential tremor were associated with a triphasic pattern of agonist-antagonist
      agonist muscle activity similar to that of normal subjects. The duration and size
      of each EMG burst was normal. The onset latency of the antagonist EMG burst was
      also normal, but the onset of the second agonist EMG burst was delayed. The delay
      in the onset of the second agonist EMG activity resulted in unopposed action of
      the antagonist muscle in the second half of each movement. As a result,
      deceleration occurred too rapidly as the hand returned past the target leading to
      a series of damped oscillations around the point of aim. The onset latency of the
      second agonist EMG burst correlated significantly with the tremor period; the
      longer the period the later the burst. We speculate that the delay in the second
      agonist burst reflects an abnormality in the timing of anticipatory muscle
      activity in essential tremor and that this may involve cerebellar mechanisms.

PMID- 8149214
TI  - Serial proton magnetic resonance spectroscopy in acute multiple sclerosis
      lesions.
AB  - Serial proton magnetic resonance spectroscopy (MRS), was carried out at 1-2
      monthly intervals on eight patients with multiple sclerosis who presented with
      evidence of a large acute cerebral white matter lesion. An MRS was obtained from
      acute lesions (volumes of interest 4-12 ml), which at presentation showed
      gadolinium-diethylenetriamine penta-acetic acid enhancement, and from similar
      volumes of normal appearing white matter lateral to the lesion and nearer the
      scalp. Follow-up ranged from 4 to 9 months (mean 6 months). Short echo spectra
      from acute enhancing lesions invariably showed the presence of large resonances
      at 0.9 and 1.3 p.p.m. compared with normal appearing white matter and healthy age
      matched controls, indicating that these peaks were not the result of voxel
      contamination from scalp fat. These resonances, which probably represent lipid
      products of myelin breakdown, were detected in lesions which had been enhancing
      for < 1 month and remained elevated for a mean of 5 months (range 4-8 months).
      The results provide evidence that short echo proton MRS can detect myelin
      breakdown products and that myelin breakdown occurs during the initial
      inflammatory stage of lesion development. The ratio of N-acetylaspartate (NAA) (a
      neuronal marker) relative to creatine was reduced in acute lesions and in normal
      appearing white matter. In six of the lesions studied there was, however, a
      subsequent rise in the NAA/creatine ratio indicating that axonal loss is not the
      only mechanism of reduction in the NAA/creatine ratio.

PMID- 8149215
TI  - Anatomical origin of deja vu and vivid 'memories' in human temporal lobe
      epilepsy.
AB  - Jackson (Brain 1898; 21: 580-90) observed that seizures arising in the medial
      temporal lobe may result in a 'dreamy state', consisting of vivid memory-like
      hallucinations, and/or the sense of having previously lived through exactly the
      same situation (deja vu). Penfield demonstrated that the dreamy state can
      sometimes be evoked by electrical stimulation of the lateral temporal neocortex,
      especially the superior temporal gyrus. Halgren et al. (Brain 1978; 101: 83-117)
      showed that the dreamy state can be evoked by stimulation of the hippocampal
      formation and amygdala and Gloor (Brain 1990; 113: 1673-94) has suggested that it
      is evoked by lateral stimulation only when the resulting after-discharge spreads
      medially. In order to resolve the relative importance of these areas, we
      considered the mental phenomena observed in epileptic patients with electrodes
      stereotaxically implanted into different brain areas for seizure localization
      prior to surgical treatment. Sixteen patients, all with seizures involving the
      temporal lobe, experienced the dreamy state either as a result of spontaneous
      seizures (nine dreamy states in six patients), or due to electrical stimulation
      (43 in 14) or to chemical activation (five in three). Deja vu and hallucinations
      of scenes were often evoked by different stimulations of the same electrode in
      the same patient. As Jackson had also observed, the dreamy state could occur
      alone but was often associated with epigastric phenomena and fear, and followed
      by loss of contact and oro-alimentary automatisms, and then by simple gestural
      automatisms, all characteristic of partial seizures beginning in the medial
      temporal lobe. Furthermore, as also emphasized by Jackson, the dreamy state was
      seldom associated with sensory illusions. Stimulation of either the neocortex (15
      occurrences), anterior hippocampus (17) or amygdala (10) could evoke a dreamy
      state. However, since fewer hippocampal and amygdala leads were stimulated than
      temporal neocortical, the proportion of medial temporal electrodes where dreamy
      states could be evoked was much higher than in the neocortex. Most responsive
      lateral temporal sites were located in the superior temporal gyrus, rather than
      the middle temporal gyrus which was significantly less responsive. In 85% of
      dreamy states evoked by medial temporal lobe stimulation, the discharge spread to
      the temporal neocortex; and in 53% of dreamy states evoked by lateral temporal
      stimulation, the discharge spread medially. Considering all dreamy states, the
      amygdala was involved (as the stimulated structure, or as the site of ictal- or
      after-discharge) in 73% of cases, the anterior hippocampus in 83% and the
      temporal neocortex in 88%.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8149216
TI  - The dynamics of cerebral dominance during unilateral limbic seizures.
AB  - An apparent discrepancy exists between the remarkable language competence of the
      isolated right cerebral hemisphere in some split-brain patients and the lack of
      language competence in some aphasic patients in whom only the left cerebral
      hemisphere has been damaged. This has led to a revival of the idea that the
      dominant cerebral hemisphere inhibits the potential functioning of its partner.
      We tested this model of interhemispheric inhibition in four patients with
      unilateral limbic seizures (three left-sided, one right-sided). While seizure
      activity was monitored with bilaterally implanted stereotactic EEG depth
      electrodes or bilateral foramen ovale EEG electrodes, the patients were tested in
      lateralized hemisphere-specific tachistoscopic recognition experiments. In two
      patients performance was correlated with the electrical pattern during prolonged
      unilateral subclinical limbic status epilepticus, and in two patients performance
      and intracranial electrical activity were compared before, immediately after and
      during the recovery phase of left limbic complex partial seizures with postictal
      aphasia. Three main findings were obtained. (i) Focal unilateral limbic seizure
      activity in the depth interferes with cognitive functions, even when unnoticed
      clinically or undetectable on the surface EEG, provided that epileptiform EEG
      activity lasts for several seconds. (ii) This interference is specific to the
      cognitive functions associated with the 'dominant' processing of the discharging
      hemisphere. (iii) Seizure-induced impairment of the 'dominant' functions of the
      discharging hemisphere is associated with improvement of performance of the same
      function by the other hemisphere. Although each patient's clinical and
      experimental situation differed, the converging results support the hypothesis of
      hemispheric interaction based upon functional inhibition for verbal processing in
      patients with a left hemispheric focus. The reverse situation, namely facial
      processing in a single case with a right hemisphere focus, remains inconclusive.

PMID- 8149217
TI  - Peripheral proprioceptive modulation in crayfish walking leg by serotonin.
AB  - In vitro serotoninergic modulation of intracellularly recorded sensory responses
      was examined in primary afferent terminals of a crayfish leg proprioceptor, the
      coxo-basal chordotonal organ (CB CO). The effects of different concentrations of
      serotonin (5-HT) on static and dynamic sensory responses were analysed following
      bath or pressure applications of the monoamine directly on the strand of the
      mechanoreceptor. Consequently, the reported effects result from the direct
      peripheral action of 5-HT on the sensory organ itself. Serotonin modulates the
      sensory activity by modifying the sensory discharge frequency. The firing
      discharge of the primary afferents is increased in a dose-dependent manner. The
      maximal effect is obtained with a concentration of 10(-6) M. Higher
      concentrations are less effective, and for 20% of the recorded cells, 10(-4) M 5
      HT induces a decrease of the sensory discharge, i.e. has an inhibitory effect.
      Alteration in the pattern of sensory firing, resulting in bursting discharge, was
      observed in some units. All the recorded sensory units were responsive to the
      neuromodulator whatever their functional properties. The effects of 5-HT lasted
      as long as the amine was applied and were reversible after wash. The results
      suggest that 5-HT could exert a modulatory action on the proprioceptive feedback,
      by peripheral action on the sensory organ. The natural modalities of 5-HT action
      are discussed on the basis of immunohistochemistry data suggesting: (i)
      connections between CB CO and central serotoninergic cells, (ii) 5-HT content in
      sensory cells of the CB CO. Since the CB CO is involved in the control of leg
      movement and position, the modulation of its primary afferents might influence
      the organization of the locomotor pattern. The functional significance of this
      peripheral sensory neuromodulation was approached by the analysis of the motor
      reflex activity.

PMID- 8149218
TI  - Activation of the human supraoptic and paraventricular nucleus neurons with aging
      and in Alzheimer's disease as judged from increasing size of the Golgi apparatus.
AB  - The supraoptic (SON) and paraventricular nucleus (PVN) of the human hypothalamus
      produce vasopressin (AVP) and oxytocin (OXT). Since in these nuclei no cells are
      lost during aging or Alzheimer's Disease (AD), factors are searched for which may
      be responsible for this remarkable stability. Earlier work in both rat and human
      indicated that the peptide synthesis of these neurons was activated in the oldest
      age groups as judged from increased neuronal and nuclear size and AVP plasma
      levels. The size of the Golgi Apparatus (GA) has proved to be a very sensitive
      parameter for the synthetic activity of these neurosecretory cells in animal
      experiments. In order to determine changes in the GA during aging and in
      Alzheimer's Disease, we applied a polyclonal antiserum against immunoaffinity
      purified MG-160, a sialoglycoprotein of the medial cisternae of the GA, on
      formalin-fixed and paraffin-embedded sections of the SON and PVN of patients
      ranging in age from 29 to 97 years. However, our standard fixation procedure
      masked antigenic sites resulting in a minimal immunocytochemical staining in most
      of the tissues examined. It appeared to be possible, however, to retrieve the
      antigen and to obtain an excellent staining of the GA by heating sections in a
      microwave oven before immunostaining. Following this procedure, an increase in
      size and intensity of the GA became apparent in individuals from about 70 years
      and older. In AD patients a similar increase in size and intensity of the
      immunostained GA was observed. Taken together, these results indicate that SON
      and PVN neurons are activated during the course of aging and also in AD and that
      this activation takes place at an earlier age than observed previously by other
      cellular parameters.

PMID- 8149219
TI  - Transthyretin expression in the rat brain: effect of thyroid functional state and
      role in thyroxine transport.
AB  - Rats were made hypo- or hyperthyroid to study the role of thyroid hormones on
      cerebral transthyretin (TTR) mRNA expression. TTR mRNA was detected by Northern
      blot in rat liver, choroid plexus and meninges but not in cultured astrocytes or
      cultured cerebral endothelial cells. No changes were found in the levels of TTR
      mRNA in liver, choroid plexus or meninges in hypo- or hyperthyroid rats compared
      with the controls. In order to investigate the main route of thyroxine transport
      from blood to brain, the distribution of [125I]thyroxine in the brain was studied
      after intravenous (i.v.) and intraventricular (i.v.c.) injection by both direct
      counting and autoradiography. While distribution of [125I]thyroxine could be seen
      throughout the brain parenchyma after i.v. injection, the labelling was confined
      to the CSF spaces after i.v.c. administration. When protein synthesis was
      inhibited by cycloheximide treatment and [125I]thyroxine was injected
      intravenously, the uptake of [125I]thyroxine in the choroid plexus decreased
      while the uptake in the cerebral cortex increased. This indicates that thyroxine
      is transported into the brain primarily through the blood-brain barrier and not
      via the choroid plexus and CSF. We discuss the possibility that TTR has a role in
      the distribution of thyroxine throughout the brain.

PMID- 8149220
TI  - Mercury (Hg2+) decreases voltage-gated calcium channel currents in rat DRG and
      Aplysia neurons.
AB  - Inorganic mercury (Hg2+) reduced voltage-gated calcium channel currents
      irreversibly in two different preparations. In cultured rat dorsal root ganglion
      (DRG) neurons, studied with the whole cell patch clamp technique, a rapid
      concentration-dependent decrease in the L/N-type currents to a steady state was
      observed with an IC50 of 1.1 microM and a Hill coefficient of 1.3. T-currents
      were blocked with Hg2+ in the same concentration range (0.5-2 microM). With
      increasing Hg2+ concentrations a slow membrane current was additionally
      activated, most obviously at concentrations over 2 microM Hg2+. This current was
      irreversible and might be due to the opening of other (non-specific) ion channels
      by Hg2+. The current-voltage (I-V) relation of DRG neurons shifted to more
      positive values, suggesting a binding of Hg2+ to the channel protein and/or
      modifying its gating properties. In neurons of the abdominal ganglion of Aplysia
      californica, studied with the two electrode voltage clamp technique, a continuous
      decrease of calcium channel currents was seen even with the lowest used
      concentration of Hg2+ (5 microM). A steady state was not reached and the effect
      was irreversible without any change on resting membrane currents, even with high
      concentrations (up to 50 microM). No shift of the I-V relation of the calcium
      channel currents was observed. Effects on voltage-activated calcium channel
      currents with Hg2+ concentrations such low have not been reported before. We
      conclude that neurotoxic effects of inorganic mercury could be partially due to
      the irreversible blockade of voltage-activated calcium channels.

PMID- 8149221
TI  - Expression of Fos in rat central nervous system elicited by afferent stimulation
      of the femoral nerve.
AB  - To investigate the distribution of Fos-like immunoreactivity (FLI) in the central
      nervous system of urethane anesthesized rats after activation of a
      somatosympathetic reflex pathway, the cut central end of the right femoral nerve
      of 17 male Wistar rats was stimulated electrically for 1 h at parameters such
      that increases in heart rate and arterial pressure were elicited. Sections of
      brain and spinal cord were incubated in anti-Fos antibody and the presence of FLI
      was detected using the ABC immunoperoxidase method. In the spinal cord FLI was
      present in the ipsilateral lumbar spinal cord (laminae 1 and 2, 4-6 and 10) and
      contralateral intermediolateral nucleus in the thoracic spinal cord. In the
      hindbrain, FLI was present in the contralateral rostral ventrolateral medulla and
      bilaterally in the cochlear nucleus, external cuneate nucleus, locus coeruleus
      and lateral parabrachial nucleus. In the midbrain, label appeared in the Edinger
      Westphal nucleus and peripeduncular nucleus on both sides. In the forebrain, FLI
      appeared bilaterally in the central nucleus of the amygdala, para- and
      periventricular hypothalamus, supraoptic nucleus, paraventricular thalamus,
      reuniens nucleus, subfornical organ and bed nucleus of the stria terminalis.
      These results define the central nervous system pathways of somatosympathetic
      reflexes and demonstrate that areas in the forebrain not previously known to be
      activated by somatosympathetic reflexes, but previously implicated in mediating
      the defense reaction, are activated by these reflexes.

PMID- 8149222
TI  - Mechanisms underlying hypothalamic temperature changes during sleep in mammals.
AB  - The mechanisms underlying hypothalamic temperature (Thy) changes across the
      ultradian wake-sleep cycle were analyzed in cats chronically implanted with EEG
      and EMG electrodes, and transducers that measured Thy and pontine temperature
      (Tp). The influence of artificially induced changes in (i) systemic blood
      temperature, (ii) heat loss from the specific heat exchangers of the head, and
      (iii) carotid artery occlusion, on Thy, Tp and ear pinna temperature (Ts) during
      waking (W), synchronized sleep (SS) and desynchronized sleep (DS) were assessed
      in animals maintained in a thermoneutral environment. The results show that the
      decrease in Thy during SS is dependent on increased heat loss from heat
      exchangers (ear pinna), whereas the increase in Thy during DS is due to an
      alteration in the arterial blood perfusion of the circle of Willis receiving an
      increased supply of warm vertebral blood that replaces a decrease in supply of
      cool carotid blood.

PMID- 8149223
TI  - Repeated exposure to hyperbaric oxygen sensitizes rats to oxygen-induced
      seizures.
AB  - Repeated exposure to increased partial pressure of oxygen (PO2) is the standard
      of care for several medical conditions. The side-effects of repeated exposure to
      hyperbaric oxygen (HBO), however, are not well defined. Previous studies have
      demonstrated that acute exposure of rats to HBO causes hypothermia that precedes
      convulsions. In the present studies, rats that were repeatedly exposed to 100%
      oxygen at 4 atmospheres absolute (ATA) pressure developed convulsions earlier
      than naive controls. There was also a trend toward less hypothermia in the rats
      repeatedly exposed to oxygen. The purpose of this study was to test the
      hypothesis that repeated exposure to HBO increases sensitivity to convulsions
      induced by HBO and to determine if the time to onset of convulsions is affected
      by the hypothermia caused by exposure to HBO. Rats were repeatedly exposed to 2
      ATA oxygen for a total of 10 days. After 72 h, these rats were challenged by
      exposure to 100% oxygen at 4 ATA pressure. Rats repeatedly exposed to HBO had
      convulsions significantly earlier than the naive controls (84 +/- 8 min compared
      to 147 +/- 11 min), and they developed significantly less hypothermia. Control
      studies suggested that the decrease in the degree of hypothermia was caused by
      both repeated exposure to oxygen and adaptation to the mild restraint used during
      oxygen re-exposures. Adaptation to restraint eliminated the hypothermia induced
      by oxygen but did not change the time to onset of convulsions. Increased
      sensitivity to convulsions was present after five exposures to 2 ATA oxygen and
      persisted for 10 days after the last 2 ATA oxygen re-exposure.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8149224
TI  - Activation of the medial septal area attenuates LTP of the lateral perforant path
      and enhances heterosynaptic LTD of the medial perforant path in aged rats.
AB  - Age-related memory impairments may be due to dysfunction of the septohippocampal
      system. The medial septal area (MSA) provides the major cholinergic projection to
      the hippocampus and is critical for memory. Knowledge of the neurobiological
      mechanisms by which the cholinergic system can attenuate age-related memory loss
      can facilitate the development of effective cognitive enhancers. At present, one
      of the best neurobiological models of memory formation is long-term
      potentiation/long-term depression (LTP/LTD). In previous studies, intraseptal
      infusion of the muscarinic agonist oxotremorine, which excites MSA neurons,
      improved memory in aged rats. The present study examined LTP and LTD in aged
      Fisher 344 rats following intraseptal infusion of oxotremorine. LTP and LTD were
      assessed using the slope of the EPSP recorded from the hilar region of the
      dentate gyrus. Induction of LTP was blocked in the lateral perforant path, but
      not in the medial perforant path, following intraseptal infusions of
      oxotremorine. The generation and amplitude of heterosynaptic LTD was enhanced in
      the medial perforant path, but not in the lateral perforant path. The results
      provide evidence that pharmacological activation of the MSA can modulate LTP and
      LTD in the hippocampus of aged rats. The implications of these results with
      respect to memory and synaptic plasticity in the hippocampus are discussed.

PMID- 8149225
TI  - Pre-emptive administration of clonidine prevents development of hyperalgesia to
      mechanical stimuli in a model of mononeuropathy in the rat.
AB  - Traumatic nerve injury in man can often result in the development of neuropathy.
      An animal model of neuropathic hyperalgesia is produced by loose ligation of the
      sciatic nerve in the rat. We have examined the effect of pre-emptive treatment
      with a number of drugs on the development of hyperalgesia in this model. Animals
      received clonidine (1 mg.kg-1, s.c.), morphine (5 mg.kg-1, s.c.), (+/-)-baclofen
      (40 mg.kg-1, s.c.), carbamazepine (50 mg.kg-1, s.c.) or vehicle (4 ml.kg-1, s.c.)
      30 min prior to loose ligation or sham-operation. Morphine- and clonidine-treated
      animals were administered a second dose of drug 6h following surgery. Twenty-six
      or twenty-nine days following surgery, the ipsilateral (ipsi.) and contralateral
      (contra.) paw withdrawal thresholds were determined using an Algesymeter. In
      vehicle-treated animals the ipsilateral paw withdrawal threshold (118 +/- 7 g)
      was significantly lower (P < 0.0001, paired t-test) than the contralateral (195
      +/- 7 g). In contrast, in animals pre-treated with clonidine no significant
      difference between ipsilateral (200 +/- 9 g) and contralateral (191 +/- 7 g) paw
      withdrawal thresholds was detected. Morphine pre-treatment was less effective in
      preventing development of hyperalgesia; however, whilst the ipsilateral (146 +/-
      18 g) paw withdrawal threshold tended to be lower than the contralateral (183 +/-
      8 g), this was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149226
TI  - Gustatory and tactile stimulation of the posterior tongue activate overlapping
      but distinctive regions within the nucleus of the solitary tract.
AB  - Both the gustatory and somatosensory systems provide necessary sensory input for
      the initiation and control of oromotor behaviors. Behavioral studies indicate
      that somatosensory input from the posterior tongue (PT) is important in
      initiating swallowing, whereas PT taste input is particularly important in
      gustatory rejection reflexes. However, there have been few studies of the central
      representation of PT gustatory or tactile responses. In the present study,
      electrophysiological multi-unit recording techniques were used to map the
      location of PT-mediated taste and tactile responses in the nucleus of the
      solitary tract (NST) of the rat. A stimulation technique that allows taste
      stimuli to be introduced directly and specifically into the papillae trenches was
      used to optimally activate PT taste receptors located within the circumvallate
      (CV) and foliate (FOL) papillae. The results demonstrated that non-PT responsive
      sites dominated the rostral half of the rostral division of NST (rNST), while PT
      responsive sites dominated the caudal half. Some PT-responsive sites extended
      into the caudal NST. Both gustatory and tactile stimuli were effective at 28% of
      PT-responsive locations (taste-tactile sites), whereas at the remaining
      locations, only tactile stimulation was effective (tactile-only sites). Although
      these two types of PT-responsive sites exhibited some anatomical overlap, their
      distributions were distinctive, with taste-tactile sites restricted medially and
      the laterally located tactile-only sites offset caudally. On the other hand,
      responses arising from stimulation of the CV and FOL exhibited no anatomical
      organization, i.e., responses to stimulation of both papillae were coexistensive.
      On average, of the four tastants used (0.01 M Na saccharin, 0.3 M NaCl, 0.01 M
      quinine hydrochloride, 0.03 M HCl), HCl was the most effective stimulus for both
      the CV and FOL. The present results delimit the regions of the NST that provide a
      substrate for the gustatory and somatosensory limbs of PT-mediated oromotor
      reflexes.

PMID- 8149227
TI  - Effect of portal infusion of hypertonic saline on neurons in the dorsal motor
      nucleus of the vagus in the rat.
AB  - Effects of hepatoportal osmo-receptive (or sodium-receptive) afferents on neurons
      within the dorsal motor nucleus of the vagus (DMV) were investigated
      electrophysiologically in urethane-chloralose anesthetized rats. Responses of 56
      spontaneously active neurons to antidromic stimulation of the ventral trunk of
      the subdiaphragmatic vagus were recorded in the left DMV. Among them, 35 neurons
      were inhibited by electrical stimulation of the hepatic branch of the vagus nerve
      (inhibitory neurons), except two neurons that were slightly excited. Effects of
      portal infusion of 3.6% NaCl were examined on 26 inhibitory neurons. Sixteen
      neurons increased their discharge rates and one neuron decreased its discharge
      rate in response to portal infusion of hypertonic saline. Thirty-five right DMV
      neurons responded to electrical stimulation of the dorsal trunk of the
      subdiaphragmatic vagus were inhibited by electrical stimulation of the hepatic
      branch of the vagus. Four neurons were excited by this stimulation. Relatively
      smaller number of neurons (5 out of 22 inhibitory neurons) increased their
      discharge rates in response to portal infusion of hypertonic saline. In
      conclusion, the response of DMV neuron observed in this experiment was
      characterized by increasing the frequency of spike discharges in response to
      portal infusion of hypertonic saline. However, these neurons were inhibited by
      electrical stimulation of the hepatic branch of the vagus nerve. These results
      suggest that the hepatoportal osmo-receptive afferents may be conveyed to the DMV
      via inhibitory synapses.

PMID- 8149228
TI  - Membrane currents in CA1 pyramidal cells during spreading depression (SD) and SD
      like hypoxic depolarization.
AB  - We used the patch clamp technique in whole-cell configuration to investigate the
      membrane current and membrane resistance of neurons in rat hippocampal tissue
      slices during spreading depression (SD) induced by high K+ solution or electrical
      stimulation and during SD-like depolarization caused by hypoxia. The potential of
      the patch pipette was referred to an extracellular micropipette electrode to
      ensure control of the true membrane potential during large shifts of
      extracellular potential, delta Vo. During both hypoxic and normoxic SD, increase
      of holding current indicated a large inward current which reached a mean maximum
      of about 1.75 nA. This virtual inward current started and ended at the same time
      as the extracellularly recorded negative delta Vo shift, but the trajectories of
      the two differed. When the membrane was clamped at strongly positive potential,
      the current during SD was outward. The average apparent reversal potential of the
      current during SD was near zero but in individual cases varied from -26 mV to +
      12 mV. During SD the input resistance decreased on the average to 43% of the
      resting control value. The decrease of the input resistance was not voltage
      dependent. The increase of holding current and decrease of resistance occurred
      with both Cs- and K-gluconate recording pipettes and was not suppressed by 2 mM
      intracellular QX-314. Voltage-gated currents disappeared during SD; a small,
      Cs(+)-resistant outward rectifying current was the last to be lost. During
      recovery, reversal potential and input resistant overshot the control level and
      then returned to normal within about 5 min. The data are consistent with change
      of both driving potential and conductance for several ions, but the decrease of
      overall membrane resistance was less than earlier estimates with other methods
      had suggested. Normoxic SD and hypoxic SD-like depolarization could not be
      distinguished by these tests.

PMID- 8149229
TI  - Opioid receptor density changes in Alzheimer amygdala and putamen.
AB  - Since opioids can influence the release of acetylcholine, substance P and a
      number of other neurotransmitters that have been implicated in the pathogenesis
      of Alzheimer's disease (AD), it is of interest to assess opioid receptor levels
      in AD. We have examined mu, delta and kappa opioid receptor binding parameters,
      binding sensitivity to a GTP analog and distribution in amygdala, frontal cortex
      and putamen of AD brain. Control brains were matched according to age, sex, post
      mortem interval and storage time. Kd values and GTP analog binding sensitivity
      did not differ in AD and control brains. Bmax values for mu ([3H]DAMGE) sites
      also appeared unaffected by in vitro binding assays. In contrast, kappa
      ([3H]U69593) and delta ([3H]DSLET) opioid receptor levels, were significantly
      changed. In AD amygdala kappa Bmax values increased from control levels of 123 +/
      12 to 168 +/- 13 fmol/mg protein, whereas densities of kappa and delta sites
      were decreased from 94 +/- 8 to 48 +/- 8 and 102 +/- 3.6 to 69 +/- 8.5 fmol/mg
      protein, respectively, in putamen. Autoradiography revealed corresponding
      differences in the distribution of kappa opioid receptors. The findings indicate
      that the kappa binding site, which is quantitatively the major opioid receptor
      class in human brain, undergoes marked changes in AD amygdala and putamen.

PMID- 8149230
TI  - Location and axonal projection of one type of swallowing interneurons in cat
      medulla.
AB  - Extracellular recordings were made from a type of relay neurons of the superior
      laryngeal nerve (SLN) afferents in the vicinity of the retrofacial nucleus (RFN)
      in either pentobarbitone-anesthetized or unanesthetized and decerebrate cats,
      which were paralyzed and artificially ventilated. A total of 26 neurons that
      could be activated both orthodromically by electrical stimulation of the SLN and
      antidromically by stimulation of the brainstem were analyzed. All 26 neurons were
      activated from the ipsilateral SLN and 13 were activated from the contralateral
      SLN with mean latencies of 7.7 ms and 11.4 ms, respectively. The majority of
      these neurons were located in the parvocellular reticular formation dorsomedial
      to the RFN and to the rostral part of the nucleus ambiguus (AMB). Antidromic
      stimulation of the medulla showed that 22 of the 26 neurons projected to the
      hypoglossal nucleus (HYP) and 19 neurons tested projected to the AMB. Of these,
      15 neurons projected to both the HYP and AMB and two projected to the lateral
      reticular nucleus as well. Seventeen neurons were tested for their behavior
      during fictive swallowing which was elicited by continual electrical stimulation
      of the SLN and monitored by the activity of the hypoglossal nerve. Twelve neurons
      showed brief (100-200 ms) burst firing at the onset of swallowing; the firing of
      the other 5 neurons were suppressed during swallowing. Both the swallowing-active
      and swallowing-inactive neurons projected to the HYP and AMB. Thus, the SLN relay
      neurons in the vicinity of the RFN might participate in the early stage of SLN
      induced swallowing by integrating inputs from SLN afferents.

PMID- 8149231
TI  - Na+ influx through Ca2+ channels can promote striatal GABA efflux in Ca(2+)
      deficient conditions in response to electrical field depolarization.
AB  - Electrical field depolarization releases gamma-aminobutyric acid (GABA) in rat
      striatal slices in the absence of external Ca2+. omega-Conotoxin GVIA (omega
      CgTx; 1-50 nM), a neuronal Ca2+ channel blocker, inhibits electrically evoked
      efflux of newly taken up [3H]GABA in a concentration-dependent manner in either
      normal or Ca(2+)-free medium. This suggests that ion influx occurs through Ca2+
      channels in the absence of external Ca2+ and contributes to the efflux of GABA.
      Reducing external Na+ concentration to 27.25 mM (low [Na+]o medium) by
      equimolarly substituting choline chloride for sodium chloride has differential
      effects on electrically evoked GABA efflux depending on the external Ca2+
      concentrations. In normal Ca2+ medium, electrically evoked GABA efflux increases
      whereas, in Ca(2+)-free medium, it is greatly inhibited when [Na+]o is reduced to
      27.25 mM. In low [Na+]o medium, GABA efflux is largely tetrodotoxin (TTX)
      sensitive, however, spike firing evoked by antidromic stimulation of striatal
      cells is inhibited. In Na(+)-free medium, resting GABA efflux increases 17-fold
      whereas evoked GABA efflux diminishes. In Ca(2+)-free medium, 70 min of
      incubation with 1-2-bis-(1-aminophenoxy)ethane-N,N,N',N' tetraacetoxy methyl
      ester (BATPA-AM, 1 microM), an intracellular calcium chelator, increases both
      resting GABA efflux and electrically evoked GABA overflow by approximately 100%.
      These results suggest that: (1) in Ca(2+)-free conditions, Na+ permeability of
      cells increases via Ca2+ channels and this profoundly affects GABA efflux. (2)
      Electrical field depolarization is likely to release GABA by directly
      depolarizing axon terminals. (3) Ca(2+)-independent GABA efflux is not promoted
      by an increase in intracellular free Ca2+ concentration via Na+/Ca2+ exchange
      processes from internal pools.

PMID- 8149232
TI  - Microcircuitry of posterior cingulate cortex in vitro: electrophysiology and
      laminar analysis using the current source density method.
AB  - We used current source density (CSD) analysis of a laminar profile of subicular
      stimulus-evoked field potentials recorded in cortical slices in vitro to
      characterize the interlaminar microcircuitry of posterior cingulate cortex.
      Neuroanatomic and electrophysiologic data indicate that subiculocingulate tract
      (SCT) afferents monosynaptically excite apical dendrites of deep laminae (V-VI)
      neurons, evoking pure EPSPs, while superficial laminae (II/III-IV) neurons are
      driven polysynaptically, evoking a mixture of longer latency EPSPs and IPSPs.
      Consistent with this model, CSD analysis of field potential laminar profiles
      supports the conclusion that activation of excitatory subicular afferent terminal
      fields in superficial laminae of cingulate cortex elicits primary monosynaptic
      activation of apical dendrites of deep lamina (V-VI) pyramids. Subsequent EPSP
      propagation to the somata of these pyramids generated synchronous action
      potential discharges which appeared to elicit delayed polysynaptic activation of
      superficial laminae pyramids and interneurons. Latency differences between SCT
      stimulus-evoked EPSPs and action potentials in superficial and deep laminae were
      minimized by stimulus train frequencies of 5-8 Hz, indicating that the proposed
      microcircuitry can show functional tuning at frequencies characteristic of
      hippocampal neuronal activity (theta). Such tuning suggests that hippocampal
      output activity frequency and phase locked to theta rhythm will be preferentially
      gated through cingulate cortex.

PMID- 8149233
TI  - Development and regulation of beta adrenergic receptors in kitten visual cortex:
      an immunocytochemical and autoradiographic study.
AB  - The developmental pattern and laminar distribution of beta 1 and beta 2
      adrenergic receptor subtypes were studied in cat visual cortex with
      autoradiography using [125I]iodocyanopindolol as a ligand and also with
      immunocytochemistry using a monoclonal antibody directed against beta adrenergic
      receptors. In the primary visual cortex of adult cats, the laminar distributions
      of both beta 1 and beta 2 adrenergic receptors revealed by autoradiography were
      very similar, with concentrations in layers I, II, III and VI. In young kittens
      (postnatal days 1 and 10), fewer beta adrenergic receptors were present, and they
      were concentrated in the deep cortical layers (V-VI) and subcortical white
      matter. Between postnatal days 15 and 40, beta adrenergic receptors increased in
      density more quickly in the superficial layers than they did in the deep and
      middle cortical layers. By postnatal day 40, the adult pattern was achieved, with
      two bands of intense binding in the superficial and deep cortical layers and a
      lower density in layer IV. Immunocytochemical techniques applied to adult cat
      cortex showed that beta adrenergic receptor-like immunoreactivity was found in
      different populations of neurons and glial cells. The immunoreactive neural cells
      were most dense in layers II, III and VI. About 50% of these immunoreactive
      neural cells were glial cells, primarily astrocytes. Immunoreactive pyramidal
      cells were mostly located in layers III and V. In layer IV, many stellate cells
      were stained. Immunoreactive astrocytes in the subplate and white matter
      progressively increased in number during development until adulthood. The pattern
      of laminar distribution and the developmental process was not affected by
      interrupting noradrenergic innervation from locus coeruleus either before or
      after the critical period. However, when visual input was interrupted by lesions
      of the lateral geniculate nucleus in young kittens (postnatal day 10), the
      density of both beta adrenergic receptor subtypes decreased significantly in the
      deep cortical layers. Lateral geniculate nucleus lesions in adult cats resulted
      in a pronounced decrease in beta adrenergic receptor density in layer IV.

PMID- 8149234
TI  - Reduction of voluntary alcohol consumption in the rat by transplantation of
      hypothalamic grafts.
AB  - Stimulation of the peripheral renin-angiotensin system has been shown previously
      to decrease the voluntary intake of ethanol in the rat. The existence of a
      separate brain renin-angiotensin system, independent from that of the periphery,
      has been widely demonstrated. The brain renin-angiotensin system plays an
      important role in the regulation of water and electrolyte balance and
      neuroendocrine function. However, the role played by this system in the
      regulation of voluntary alcohol consumption has not yet been studied. The goal of
      the present work was to assess the feasibility of decreasing the voluntary
      alcohol intake in a strain of rats (Rapp SS/Jr rats) that have a genetic
      deficiency responsible for a low activity of the renin-angiotensin system and
      elevated alcohol intake. Adult Rapp SS/Jr rats received intraventricular
      transplants of fetal hypothalamic grafts (from normal donors), known to contain
      angiotensin-immunoreactive cell bodies. Our studies revealed that angiotensin
      immunoreactivity in the cell bodies and fibres in the paraventricular, supraoptic
      and suprachiasmatic nuclei of the hypothalamus in Rapp SS/Jr rats was markedly
      reduced. Animals that had surviving grafts containing angiotensin-immunoreactive
      cell bodies in the dorsal third ventricle--but not in the ventral third
      ventricle, in the lateral ventricles, or sham operated animals--had a 40%
      decrease of their voluntary alcohol intake, when compared to their intake before
      surgery, or to the control group. However, water consumption was not reduced in
      both the sham and transplanted animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149235
TI  - Neuritogenesis of retinal ganglion cells is differentially promoted by target
      extract.
AB  - Labeled retinal ganglion cells from neonatal rats extended neurites in
      dissociated cell culture as a cell type-specific response to the influence of a
      superior collicular extract. The molecule responsible for this neuritogenic
      effect is soluble and non-dialysable (> 12 kDa). Nerve growth factor had a
      neuritogenic effect both on ganglion cells and other types of retinal cells.

PMID- 8149236
TI  - Increased levels of the excitotoxin quinolinic acid in spinal cord following
      contusion injury.
AB  - Products of inflammatory phagocytes are potential contributors to secondary
      pathology following spinal cord trauma. In the present study we quantified the
      levels of the neurotoxin and product of activated macrophages, quinolinic acid
      (QUIN), in the lower thoracic spinal cord of adult guinea pigs 5 days after brief
      compression injury. At the injured site (T13), elevations in tissue QUIN levels
      (> 10-fold) accompanied proportional increases in the activity of indoleamine-2,3
      dioxygenase (> 2-fold) and the concentrations of L-kynurenine (> 2.5-fold). In
      contrast, no significant changes occurred in two uninjured regions examined
      compared to controls, namely cervical spinal cord (C2) and the somatosensory
      cortex. Further studies of QUIN as a potential contributor to spinal cord injury
      are warranted.

PMID- 8149237
TI  - Mapping extracellular excitability in an insect mechanoreceptor neuron.
AB  - The cockroach tactile spine contains a single bipolar mechanosensory neuron.
      Extracellular stimulation of the neuron is possible by cutting the spine and
      lowering a microelectrode into the lumen, where the neuron is located, but
      neither the microelectrode nor the neuron can be visualized during stimulation.
      The threshold for electrical stimulation of the neuron was measured as a function
      of spatial position in the lumen. The spine was then fixed and serially sectioned
      for computer-aided reconstruction. Alignment of threshold measurements with
      reconstructions produced maps of excitability around the neuron. The lowest
      threshold was always close to the sensory dendrite or the adjacent soma. These
      results are discussed in terms of models of action potential initiation in this
      class of sensory neurons.

PMID- 8149238
TI  - Involvement of EP3 subtype of prostaglandin E receptors in PGE2-induced
      enhancement of the bradykinin response of nociceptors.
AB  - Prostaglandin E2 augments bradykinin-induced discharges of polymodal receptors as
      studied in vitro preparations. The antagonist and agonists for three subtypes of
      EP receptors were used to determine which subtype is involved in this phenomenon.
      The agonist for EP3 (M&B28767) simulated the PGE2-induced effect but not for EP2
      (butaprost). The antagonist for EP1 (AH6809) did not suppress the effect. These
      findings indicate the involvement of the EP3 receptor subtype in the effect.

PMID- 8149239
TI  - Adult rabbit brain synthesizes retinoic acid.
AB  - Tissues of adult rabbit brain were shown to enzymatically oxidize retinol and
      retinaldehyde to retinoic acid, a potent stimulator of gene expression. Rates of
      retinoic acid synthesis by the cerebrum, cerebellum, and meninges were comparable
      to, or exceeded, rates measured with rat liver, an organ known to have a
      relatively high capacity to synthesize retinoic acid. These results, taken
      together with previous observations that the adult brain contains retinoic acid
      activated transcription factors and cellular retinoid-binding proteins, suggest
      that retinoids may play an important role in the adult central nervous system.

PMID- 8149240
TI  - Distribution of N-methyl D-aspartate (NMDA) receptor mRNAs in the rat
      suprachiasmatic nucleus.
AB  - Photic entrainment of the circadian oscillator located in the hypothalamic
      suprachiasmatic nucleus (SCN) is considered to be mediated at least partly by
      release of glutamate from the retinal presynaptic nerve terminals acting via a
      NMDA receptor. Several NMDA receptor subtypes have been cloned and expressed in
      model systems. The NMDA-R1 subtype is essential for the function of the NMDA
      receptor, and the multiple NMDA-R2(-A, -B, or -C) subunits potentiate and
      differentiate the function of the NMDA receptor by forming different heteromeric
      configurations with NMDA-R1. The aim of this study was to use in situ
      hybridization histochemistry with oligonucleotide sequences (42-48-mer) labeled
      with 35S to detect whether NMDA receptor mRNA is present in the rat SCN, and if
      so, to characterize which receptor subtypes occur. In order to identify the
      precise location of NMDA receptor mRNAs within the SCN, sections were dipped in
      emulsion and cellular resolution was achieved. The hybridization revealed a high
      abundance of NMDA-R1 mRNA in the SCN as well as in many other forebrain areas.
      The NMDA-R1 expressing cells were distributed throughout the SCN. NMDA-R2A and
      NMDA-R2B mRNAs were found in the hippocampus, but not in the SCN. In contrast,
      NMDA-R2C mRNA was found in relative high amounts in the rat SCN, but not in other
      hypothalamic areas. In dipped sections, it was evident that the localization of
      NMDA-2RC was mostly confined to the dorsomedial part of the SCN. Thus, the rat
      SCN contains a specific combination of NMDA receptor mRNA subtypes not found in
      other forebrain structures. These observations are consistent with the hypothesis
      that glutamate mediates the effect of light on entrainment of the circadian
      oscillator.

PMID- 8149241
TI  - Colocalization of Fos- and glucocorticoid receptor-immunoreactivities is present
      only in a very restricted population of dorsal horn neurons of the rat spinal
      cord after nociceptive stimulation.
AB  - Immunocytochemical techniques were used to study the colocalization of proto
      oncogene c-fos protein (Fos)-like immunoreactivity and of glucocorticoid receptor
      immunoreactivity in the spinal cord dorsal horn of adult male rats after
      nociceptive stimulation. About 5-10% of the stimulus evoked Fos-immunoreactive
      profiles colocalized glucocorticoid receptor immunoreactivity. The results
      suggest the possibility of a corticosteroid action in a small neuronal population
      of the dorsal horn implicated in processing nociceptive inputs.

PMID- 8149242
TI  - Differential controls of small and large motor unit activity in the masseter
      muscle with incisal stimulation in humans.
AB  - The activity of masseter motor units with different spike amplitudes was recorded
      and reflex responses by force stimulation of an incisor were analyzed in humans.
      The effects of reflex responses varied depending on the level of prestimulus
      firing frequency (background activity, BGA). When small amplitude motor units and
      large amplitude motor units were tested at the same level of BGA, the former
      tended to exhibit excitatory reflexes and the latter inhibitory ones.

PMID- 8149243
TI  - Colocalization of calbindin-D28k with vasopressin in hypothalamic cells of the
      rat: a double-labeling immunofluorescence study.
AB  - By use of a double-labeling immunofluorescence method, we examined whether
      vasopressin-containing cells possess a calcium-binding protein, calbindin-D28k,
      in the hypothalamus of the rat. Subpopulations of vasopressin-containing cells
      varied in their ability to possess calbindin-D28k immunoreactivity in different
      regions. In the supraoptic nucleus, most vasopressin-immunoreactive cells were
      also stained for calbindin-D28k. By contrast, in the magnocellular part of the
      hypothalamic paraventricular nucleus, all vasopressin-labeled cells lacked
      calbindin-D28k. In the suprachiasmatic nucleus, no calbindin-D28k was found in
      vasopressin-stained cells. This study shows a further characterization of
      vasopressin-containing cells of the rat hypothalamus.

PMID- 8149244
TI  - Intrahippocampal transplants of septal cholinergic neurons: choline
      acetyltransferase activity, muscarinic receptor binding, and spatial memory
      function.
AB  - Recent studies have demonstrated that intrahippocampal cholinergic septal grafts
      can ameliorate deficits in spatial memory function and hippocampal cholinergic
      neurochemical activity in animals with disruptions of the septohippocampal
      pathway. Further studies have revealed that hippocampal cholinergic activity, as
      measured by high affinity choline uptake, correlates significantly with
      performance on tests of spatial memory function. The present study was designed
      to examine the effect of cholinergic septal grafts on reversing deficits in
      hippocampal choline acetyltransferase activity and on normalizing muscarinic
      receptor binding in animals with lesions of the septohippocampal system, and to
      examine the correlations between these cholinergic parameters and performance of
      spatial memory tasks. The results of this study indicated that in animals with
      lesions plus septal grafts, hippocampal ChAT activity was restored significantly
      and muscarinic receptor binding was normalized to a level not different from the
      control animals. Regression analyses indicated that ChAT activity was
      significantly correlated with performance on spatial reference memory, spatial
      navigation and spatial working memory, while muscarinic receptor binding
      correlated significantly with spatial reference memory performance.

PMID- 8149245
TI  - Fos induction by nerve growth factor in the adult rat brain.
AB  - The distribution of Fos, the protein product of the immediate early gene c-fos,
      was studied with immunocytochemistry in the adult male rat brain after nerve
      growth factor (NGF) administration. NGF was injected in the lateral cerebral
      ventricle through a previously implanted cannula. The total number of Fos
      immunoreactive (ir) neurons in the brain was 2-3 times higher after NGF
      administration than in control animals (untreated or injected with cytochrome c).
      With respect to control rats, in the NGF-treated cases Fos-ir cells were more
      numerous in the anterior olfactory nucleus, in the medial prefrontal and anterior
      cingulate cortices, in the basal forebrain, in the preoptic and ventromedial
      nuclei of the hypothalamus, as well as anterior hypothalamic area, in the
      thalamic midline nuclei, and in some brainstem structures, such as the
      parabrachial nucleus. The relative quantitative increase of Fos-ir neurons varied
      in the different structures. In addition, Fos-ir neurons were evident after NGF
      administration in areas devoid of immunopositive cells in control animals. These
      included: frontoparietal and occipital cortical fields, the hypothalamic arcuate
      nucleus, and many brainstem structures, such as the dorsal nucleus of the lateral
      lemniscus, posterodorsal tegmental, medial and lateral vestibular, ventral
      cochlear, and prepositus hypoglossal nuclei. These findings demonstrate that the
      intracerebroventricular administration of NGF can induce c-fos expression in
      neurons in vivo. The distribution of Fos-ir neurons indicates that NGF can induce
      activation of functionally and chemically heterogeneous neuronal subsets in the
      brain.

PMID- 8149246
TI  - Ventral tegmental injections of morphine but not U-50,488H enhance feeding in
      food-deprived rats.
AB  - Food-deprived rats received microinjections of the preferential mu opiate
      morphine or the selective kappa opiate U-50,488H (0.1, 1 and 10 nmol) into the
      ventral tegmental area (VTA). Meals were divided into discrete segments so that
      repeated measures of the speed of eating and the latency to initiate eating could
      be obtained. Morphine produced a dose-dependent increase in the speed of eating.
      Injections of saline or U-50,488H into the VTA or injections of morphine dorsal
      to the VTA were ineffective. Neither morphine nor U-50,488H had a significant
      effect on the latency to initiate feeding. These data suggest that mu but not
      kappa opioid receptors in the VTA are involved in the regulation of feeding in
      food-deprived rats.

PMID- 8149247
TI  - Neonatal sciatic nerve lesion triggers the sprouting of fibers in the
      contralateral ventral root of the rat.
AB  - We explored the possibility that unilateral neurectomy of the sciatic nerve of
      the rat at the neonatal stage triggers sprouting of afferent fibers in the
      contralateral ventral root. 3 months after neonatal sciatic neurectomy, the
      numbers of both myelinated and unmyelinated fibers in the L5 and L3 ventral roots
      were counted on electron micrographic montages. Age-matched littermates were used
      as unoperated controls. To identify regenerating axons, electron microscopic
      immunohistochemistry was done on the ventral roots using antibody against growth
      associated phosphoprotein (GAP-43). Neonatal sciatic neurectomy resulted in: (1)
      about a three-fold increase in the number of unmyelinated fibers in the
      contralateral L5 ventral root as compared with the unoperated control; (2) about
      a 25-fold increase in the number of unmyelinated fibers in the ipsilateral L5
      ventral root as compared with the control; (3) approximately 25% of the
      unmyelinated fibers in the contralateral L5 ventral root expressing GAP-43; and
      (4) no significant change in the number of unmyelinated fibers in the L3 ventral
      root of either side as compared with the control. The data suggest that a
      neonatal sciatic neurectomy of the rat triggers sprouting of unmyelinated
      afferent fibers in the ventral root of the contralateral as well as the
      ipsilateral side. The sprouting is restricted, however, to spinal segments which
      receive inputs from the sciatic nerve.

PMID- 8149248
TI  - Localisation of muscarinic (m1) and other neurotransmitter receptors on
      corticofugal-projecting pyramidal neurones.
AB  - Experimental lesions and quantitative autoradiography were used to investigate
      the cellular localisation of receptors. Lesions were produced by intrastriatal
      injections of either volkensin or ricin, only the former is retrogradely
      transported. Volkensin treatment caused significant losses in Fr1/Fr2 of
      neocortex in the number of infragranular pyramidal neurones and binding to deep
      cortical layers of both [3H]pirenzepine (muscarinic cholinergic m1 receptors) and
      [3H]kainate (kainate sensitive glutamate receptors). In common with previous
      findings, which also showed sparing of interneurones, supragranular pyramidal
      neurones were not reduced in number and the binding to deep cortical layers of
      [3H]8-hydroxy-2-(n-dipropylamino)tetralin (serotonin 1A receptors) was reduced.
      Significant increases in [3H]prazosin binding to both total alpha adrenoceptors
      and the alpha 1b subtype were observed in superficial layers. Adrenoceptors were
      not decreased in any layer. The binding of [3H] GABA to GABAA receptors was not
      affected at all. Muscarinic receptors and pyramidal neurones were also reduced in
      deep cortical layers of Par1/Par2 in common with serotonin 1A (5-HT1A) receptors
      and total alpha receptors were significantly decreased in the middle layers.
      Overall m1 and kainate receptors were less affected than 5-HT1A receptors. The
      results are discussed in terms of the biology of cortical pyramidal neurones,
      drugs for Alzheimer's disease and novel ligands for improving human brain in vivo
      scanning techniques.

PMID- 8149249
TI  - Variations in soleus H-reflexes as a function of plantarflexion torque in man.
AB  - The purpose of this study was to evaluate the effects of the levels of voluntary
      isometric contraction on the Hoffman reflex in human soleus and medial
      gastrocnemius (MG) muscles. H-reflexes were recorded in sixteen healthy adults at
      each of 16 isometric plantarflexion (pf) torque levels ranging from 0-100% of
      their maximum voluntary isometric contraction (MVC) and were elicited at two
      intensities of stimulation: (i) supramaximal for M-response and (ii) a submaximal
      stimulus that produced an H-reflex in soleus that was 50% of maximum H-reflex at
      rest. The H-reflex peak-to-peak amplitudes were linearly related to pf torque
      levels ranging from 0 to 50% MVC at both supramaximal and submaximal stimulus
      intensities. The slope of this relationship was higher for the submaximal
      stimulation. Beyond 60% of MVC, the soleus H-reflex amplitude showed no further
      increase with increasing pf torque for both stimulus intensities. Thus, beyond 50
      60% of MVC the soleus H-reflex does not provide an accurate measure of soleus
      motor neuron pool excitability. Further experimental results showed that the H
      reflex amplitude at a given torque level depended on whether torque was
      increasing or decreasing. When torque was increasing, the amplitude of the H
      reflex was larger than when the same torque was maintained at a constant level.
      In contrast, if the torque was decreasing, amplitude of the reflex was lower than
      when torque was increasing. Therefore, variations in H-reflex amplitudes at a
      given torque level may be more closely correlated to the direction of the ongoing
      contraction than to the actual muscle force being produced at the time the H
      reflex is elicited.

PMID- 8149250
TI  - [Results of twenty year follow-up of patients with inoperable prostate cancer
      (stage C) treated by radiotherapy. Report of a national multicenter study].
AB  - This is a report on a National Cooperative study of Radiotherapy for inoperable
      patients with cancer of the prostate: 372 patients with adenocarcinoma of the
      prostate, stage C, received radiotherapy from 1967 to 1973, according to a very
      strict protocol. With minor variations, all patients received the same total
      dose: 7000 cGy in 47 days or 7500 cGy in 54 days. Mild episodes of hematuria and
      rectal bleeding were observed in a number of patients: urethral and rectal
      strictures also resulted in a few cases, but were no life-threatening
      complications. A total of 177 patients (47%) died from prostatic cancer, mostly
      bony metastases that may have been present when the patients were first seen;
      death from prostatic cancer decreased as the years went by. Only 4 patients (1%)
      were lost to follow-up, only one before ten years, and none had evidence of
      cancer when last seen. However, 167 (44%) of the 372 patients lived for various
      periods of times and died without ostensible evidence of prostatic cancer. In
      addition 24 were still living after 20 years. Thus, more than half of these
      elderly inoperable patients treated by radiotherapy lived to die of something
      else.

PMID- 8149251
TI  - [Current questions and controversies on the treatment of prostate cancer].
AB  - The treatment of prostatic adenocarcinoma is the subject of debate and
      controversy at all stages of the disease. At the initial "subclinical" stage,
      discovered in transurethral resection or prostatectomy specimens, the
      conservative approach generally adopted should sometimes be replaced by curative
      treatment in young patients or in the case of high grade cancers. The localised,
      intraprostatic stage is amenable to curative treatment. However, radical
      prostatectomy may not be indicated in the presence of lymph node metastases and
      the discovery of positive margins on histological examination of the resection
      specimen raises the question of the necessity and the chronology of complementary
      treatments. At the stage of locally advanced cancer, all therapeutic modalities
      have been proposed in various combinations. The most controversial question
      concerns neoadjuvant endocrine therapy prior to radical prostatectomy. Metastatic
      disease is treated by endocrine therapy. However, the necessity of complete
      androgen blockade chemotherapy has still not been demonstrated. No effective
      therapeutic solution has yet been found for "endocrine escape", but a number of
      palliative measures should improve the quality of the patient's limited survival.

PMID- 8149252
TI  - [Health education about alcohol; need to abandon a purely quantitative message].
AB  - In health education, the foundations of the classic message of moderate alcohol
      consumption, based on the notion that there exist safe thresholds below which one
      can drink without danger, have become outdated. This is due to various factors:
      the discovery of additional routes for the oxidation of alcohol into
      acetaldehyde; epidemiological studies on the relationship between dose and effect
      that have challenged classic thresholds; and, finally, the rising emphasis on the
      role played by background, now better understood because of the opening of new
      physiological perspectives and evidence of the involvement of genetic factors.
      This role has led to an underling of the notions of vulnerability and inequality
      in relation to alcohol. The message of health education must therefore be one of
      "alcohol risk", a message combining both the factor of quantity ingested and the
      factor of background. Without giving rise to prohibitionist attitudes, it should
      lead to responsible individual behavior where alcohol is concerned.

PMID- 8149253
TI  - [The obstetric emergency].

PMID- 8149254
TI  - [Emergencies in neurosurgery].

PMID- 8149255
TI  - [Population genetics, immunologic evaluation and Buerger's disease. Projection
      through a personal study comprising 127 cases of juvenile arteriopathy].
AB  - The analysis of anamnestic, clinical and arteriographic parameters in 127 young
      patients with arterial disease of the lower limbs allowed a definite distinction
      between thromboangiitis obliterans (TAO) and early-onset atheroma, even if the
      etiopathogenic of TAO is still obscure. The HLA gene frequency has been
      determined in 54 patients (14 TAO, 40 early atheroma) and has been compared with
      local blood donors and with caucased subjects from the IXth Workshop. The results
      (higher frequency of HLA A28, AX, B53 and BX in the TAO group) have, however, a
      dubious significance. Furthermore, there were no differences between TAO and
      early atheroma in a comparative study of immunological parameters (anti-nuclear
      antibodies, circulating immune complexes, C3, C4 and CH50, cryoglobulin) in 72
      patients (22 TAO, 50 early atheroma). So, neither a genetic predisposition nor a
      dysimmunity could be involved in the pathogenesis of TAO.

PMID- 8149256
TI  - [Role of surgical visceral manifestations in the natural history of the acquired
      immunodeficiency syndrome in adults].
AB  - The surgical effects of AIDS in adults are rather frequent. On the basis of 74
      cases, from 1985 to 1992, that we have studied clinically, by imaging procedures,
      biology, previous and long term follow-up, we have tried to set up the place of
      these effects in the natural history of the disease. The infectious complications
      must distinguished from tumorous ones. As to the first, we must underline the
      alithiasic cholecystitis, more often by cytomegalovirus, the sclerosing
      cholangitis and anorectal sepsis. So far as concerns tumors, note should be taken
      of the visceral Kaposi's tumors, and the non-hodgkins lymphomas which may given
      mass effect, haemorrhage or perforation. The common carcinomas shows an abnormal
      swiftness of growth. The complications chiefly happen at the C stage, so they are
      mixed up with other effects and their numerous treatments. Thereafter, the
      diagnosis and the treatment are difficult as well. In spite of some success in
      the short term on the complications themselves, the surgical procedures did not
      alter the general course of the disease. The advanced stage of this one leads to
      a high rate of mortality. Fifty-three of our patients died in a short time. We
      lost sight of 10 but in a critical state. The other 11 are still now in
      remission.

PMID- 8149257
TI  - [Modes of management of people infected with human immunodeficiency virus (HIV)].

PMID- 8149258
TI  - [Recent developments in the epidemiology and prevention of rabies].
AB  - Rabies is one of the oldest known diseases and man has been combatting it for
      many centuries. In many parts of the world, however, especially in the developing
      countries, success in controlling the disease will remain limited. Sanitary
      prophylaxis of rabies has reached its limit due to two factors: the difficulty of
      confining or eliminating all the vector animals, and the growing public
      opposition to the use of such measures. Medical prophylaxis can be undertaken in
      two ways: vaccination by the parental route or oral vaccination. The former has
      reached its limit in many developing countries, where its high cost is considered
      to outweigh the benefit to public health. Oral vaccination, on the other hand,
      has achieved spectacular success in Europe, where it is being used to
      progressively eliminate fox rabies. This technique could applied to dogs as soon
      as the scientific and technical prerequisites have been clearly defined.

PMID- 8149259
TI  - [Child victims of house fires in France. Mortality, morbidity, prevention].
AB  - Children injuries by house fires in France are the cause of a severe mortality
      (sixty deaths in average each year) and of a morbidity for the survival due to
      smoke toxicity (oxygen deprivation and inhalation of toxic gases--CO and HCN) and
      to thermal burns. Epidemiological studies show that young children (0 to 4) are
      specially concerned by this threat and that the deaths occurred more often in
      some part of France (Nord-Pas-de-Calais Region). A special strategy for this
      prevention should be applied in France, the same available in USA, Sweden and UK,
      including information on the behavior one should have with children: never leave
      them alone and escape with them as soon as possible out of the smoke. The
      usefulness of smoke detectors should be confirmed by French administration and
      recommended to the public, since they have had effective results in other
      countries.

PMID- 8149260
TI  - [Auditory risks related to use of the walkman].

PMID- 8149261
TI  - [Peroxidation of human high density lipoproteins by oxygen-derived free
      radicals].
AB  - The involvement of low density lipoprotein (LDL) peroxidation in atherogenesis is
      now admitted. The oxidation of high density lipoproteins (HDL) could contribute
      to the atherogenic process, by limiting their capacity to accept cholesterol from
      cell membranes. In this work, we studied the human HDL peroxidation initiated by
      OH. or OH./O2.- free radicals generated by gamma radiolysis. This method allows a
      quantitative and selective production of free radicals, and the resulting
      oxidation is less drastic than the chemical one. HDL oxidation was followed, as a
      function of the radiation dose, by the disappearance of endogenous vitamin E, the
      formation of thiobarbituric acid-reactive substances (TBARS) and the fluorescence
      at 440 nm. Human HDL turned out to be oxidizable by hydroxyl free radicals and
      oxygen potentiated this effect. The oxidative modification of HDL, leading to a
      rigidification of the HDL envelop, could contribute to reduce the ability of HDL
      to stimulate efflux of cholesterol from tissues.

PMID- 8149262
TI  - [Humoral and cellular immunity in influenza virus infection].
AB  - In man, humoral immunity against influenza viruses (induced by presently
      available vaccines) is exerted by local and circulating antibodies against two
      surface antigens of the virions: hemagglutinin (HA) and neuraminidase (NA).
      Within each major antigenic type of influenza virus (A, B and C) these antibodies
      are strictly specific of the HA and NA characterizing variable sub-types, which
      appear in the course of time from an epidemic to the next one. There exists
      however a cell-mediated facet of immunity: study of the experimental infection of
      laboratory mice with mouse-adapted viruses has shown that this cellular immunity
      is type-specific and therefore covers all the sub-types of a given type of virus.
      This heterologous immunity is primarily mediated by cytotoxic T lymphocytes (CTL)
      which recognize an internal nucleoprotein (NP) common to all the sub-types. These
      CTL are able to lyse influenza virus-infected cells and contribute to local
      production of interferon in the course of infection. Such mechanisms likely play
      a major role in the natural resistance of the host to this infection. Thanks to
      the molecular characterization of the NP protein, it is now possible to conceive
      the design of vaccines endowed with a wider spectrum than those presently used;
      in association with the latter, it should become possible in the future to
      stimulate efficiently both facets of anti-influenza immunity.

PMID- 8149263
TI  - [AIDS and drug addiction in the prison environment].

PMID- 8149264
TI  - Radiologic features of pulmonary tuberculosis: an assessment of 188 cases.
AB  - To assess the radiologic patterns of presentation of active pulmonary
      tuberculosis, the authors studied all patients with active, culture-proven
      pulmonary tuberculosis who presented in British Columbia between May 1989 and May
      1991. The chest radiographs were assessed by two observers. Epidemiologic data
      were collected to allow examination of differences among ethnic groups. The 188
      patients ranged in age from 1 to 96 (median 54) years; only 2 were less than 20
      years of age. Thirty of the 188 patients (16%) presented with clinical and
      radiologic findings consistent with primary tuberculosis; the other 158 (84%) had
      postprimary disease. Of the second group, typical upper lobe infiltrates were
      seen in 126 (80%). Less common manifestations included lymphadenopathy (in 14
      cases), isolated nodular tuberculoma (in 10), isolated involvement of the lower
      lung zones (in 10), cavities with air-fluid levels (in 6) and isolated pleural
      effusion (in 2). The authors conclude that the characteristic upper lobe
      infiltrates of postprimary disease remain the most common form of presentation of
      active tuberculosis in adults. However, atypical presentation, due to either an
      unusual pattern of postprimary tuberculosis or to primary tuberculosis, may be
      seen in up to 30% of patients.

PMID- 8149265
TI  - Focal nodular hyperplasia of the liver--an imaging conundrum.
AB  - Focal nodular hyperplasia is a common benign tumour of the liver that usually
      does not require treatment. This tumour can be difficult to distinguish
      noninvasively from other lesions in young patients that may require intervention,
      such as hepatic adenoma and fibrolamellar carcinoma. The authors report three
      cases of histologically proven focal nodular hyperplasia and one case in which
      the imaging features strongly suggested this tumour. These cases illustrate many
      of the variable imaging features of focal nodular hyperplasia. The authors review
      the typical imaging findings for focal nodular hyperplasia, hepatic adenoma and
      fibrolamellar carcinoma, indicate the areas of overlap that make noninvasive
      diagnosis impossible and discuss the role of percutaneous biopsy in establishing
      the definitive diagnosis.

PMID- 8149266
TI  - The influence of referral protocols on the utilization of magnetic resonance
      imaging: evidence from Manitoba.
AB  - The relative scarcity of magnetic resonance imaging (MRI) capacity in most
      Canadian jurisdictions has created pressures to develop guidelines on appropriate
      clinical indications for examination by this method. The objective of this study
      was to assess the influence of referral protocols on the utilization of MRI
      services. Three neuroradiologists and one radiologist reviewed the indications
      for MRI for 198 referrals to the facility at St. Boniface General Hospital in
      Winnipeg (99 from outside Manitoba and 99 from within the province), selected at
      random from patients seen between Jan. 1 and Dec. 31, 1991, for suspected
      disorder of the brain or the spine. Out-of-province referrals had not been
      subject to referral protocols, whereas those from within Manitoba had been
      subject to such protocols. At least three of the four radiologists agreed on
      whether an examination was appropriate in 175 of the 198 cases (88.4%). Out-of
      province referrals were significantly more likely to be considered inappropriate
      for MRI: 24 (24%) of the referrals from outside Manitoba were judged
      inappropriate by three or more reviewers, whereas only 10 (10%) of the referrals
      from within Manitoba were judged inappropriate (chi 2, p < 0.01). Of the 19 cases
      that were judged inappropriate for MRI by three or more reviewers and that
      yielded abnormal findings, unique clinical information was derived from the
      examination in only 1 (5%); in contrast, of the 85 cases that were judged
      appropriate for MRI by three or more reviewers and that yielded abnormal
      findings, unique information was found in 47 (55%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8149267
TI  - Radiation dose associated with spiral computed tomography.
AB  - Spiral computed tomography (CT) has recently become available as a practical
      diagnostic tool; its introduction has created the need for a comprehensive
      understanding of the magnitude and distribution of the radiation dose to the
      patient. Dose distributions for conventional and spiral CT were measured with
      thermoluminescent dosimeters loaded in standard phantoms and then compared to
      determine the validity of using standard dose descriptors for assessing the dose
      delivered during spiral CT. Two dose descriptors applied to conventional CT, the
      CT dose index and the multiple-scan average dose, were found to be adequate for
      quantifying the dose delivered by spiral CT.

PMID- 8149268
TI  - Aneurysms of the posterior cerebral and superior cerebellar arteries in a child.
AB  - The authors describe an 11-year-old girl with two aneurysms in the posterior
      circulation of the brain; one of the lesions was treated surgically, and the
      second resolved spontaneously. The utility of magnetic resonance imaging and
      angiography in the detection and follow-up of the lesions is discussed.

PMID- 8149269
TI  - Parapharyngeal branchial cleft cyst presenting with cranial nerve palsies.
AB  - The authors report a case of branchial cleft cyst for which the location and
      presentation of the lesion were unusual. This abnormality should be considered in
      the differential diagnosis of cystic lesions of the parapharyngeal space. The
      presence of multiple cranial nerve palsies in association with a mass in this
      region does not necessarily indicate a neoplastic lesion.

PMID- 8149270
TI  - Magnetic resonance imaging in moyamoya disease.
AB  - The authors describe the characteristic magnetic resonance imaging (MRI) findings
      of moyamoya disease in a 51-year-old woman; the disease was confirmed by
      angiography. MRI demonstrated well the occlusions and collateral vessels that
      typically occur secondary to this rare disease. Although hemorrhagic
      complications often result in a poor prognosis for patients with moyamoya
      disease, the patient described here recovered.

PMID- 8149271
TI  - Benign mucous membrane pemphigoid: treatment of esophageal stricture.
AB  - The authors describe a 35-year-old man who has had benign mucous membrane
      pemphigoid from the age of 12 years. Upper esophageal stricture, a rare
      complication of the syndrome, developed when he was 24 years old. This recurrent
      condition has been followed for 11 years. It was treated initially, for 6 years,
      with esophagoscopy and bougie dilatation. Balloon dilatation under fluoroscopic
      guidance was then substituted for bougienage; this procedure has been performed
      successfully 10 times over the last 5 years and remains the patient's preferred
      treatment. The mean period for recurrence of symptoms has been 5 months. Several
      previous reports of this condition describe treatment with esophagoscopy and
      bougie dilatation, but there has been no previous report of interventional
      radiology with balloon dilatation.

PMID- 8149272
TI  - Breast gigantism due to D-penicillamine.
AB  - One of the alarming side effects of D-penicillamine therapy is massive breast
      hypertrophy. This effect has been observed in nine patients to date. The author
      presents another case, including the first description of mammographic findings.

PMID- 8149273
TI  - Intrathoracic scapular prolapse after thoracotomy.
AB  - The authors present a case of intrathoracic prolapse of the scapula after
      anterolateral thoracotomy. Although shoulder deformity and weakness have been
      reported after thoracotomy, intrathoracic scapular displacement has not
      previously been described. Debilitation and steroid therapy may have contributed
      to weakness of the chest wall. Computed tomography of the thorax was essential in
      making the diagnosis.

PMID- 8149274
TI  - Carney syndrome: radiologic features.
AB  - The Carney syndrome, first described in 1977, is characterized by the association
      of three rare tumours of different origin: gastric leiomyosarcoma, functioning
      extra-adrenal paraganglioma and pulmonary chondroma. The authors describe a young
      woman in whom gastric leiomyosarcoma, retroperitoneal paraganglioma and pulmonary
      chondroma developed. Radiologists should be aware of the possible association of
      these three types of neoplasia, because simple radiologic examination of the
      abdomen and the chest may lead to the correct diagnosis.

PMID- 8149275
TI  - Residents' corner. Answer to case of the month #24. Syphilitic aortic aneurysm.

PMID- 8149276
TI  - Transient global amnesia.

PMID- 8149277
TI  - Pulmonary manifestations of coccidioidomycosis.
AB  - Pulmonary coccidioidomycosis is a fungal disease seen primarily in the
      southwestern United States and Mexico. However, with the advent of mass travel it
      is being seen increasingly in countries outside the zone where it is endemic.
      Pulmonary coccidioidomycosis, which has a high infectivity, is acquired by
      inhalation of fungal arthrospores. Its infectivity is increased in
      immunosuppressed patients, particularly those with the acquired immunodeficiency
      syndrome. Because of these factors, it is important for radiologists
      (particularly those practising outside the area of endemicity) to recognize the
      various manifestations of this disease. The authors review the major clinical
      syndromes and their radiologic manifestations.

PMID- 8149278
TI  - Optimal imaging techniques for locating leaflets after escape from prosthetic
      heart valves.
AB  - The authors report two cases of leaflets escaping from an Edwards-Duromedics
      bileaflet prosthetic heart valve (Baxter-Edwards Division, Baxter Healthcare
      Corp., Irvine, Calif.). Several imaging techniques were used in attempts to
      locate the leaflets. Only computed tomography (CT) led to conclusive results.
      Because progressive extrusion through the arterial wall was documented surgically
      in these cases, the authors recommend that CT be performed as early as possible
      after a leaflet escapes, even in asymptomatic patients. Extrusion through the
      arterial wall precludes percutaneous intravascular movement or retrieval of
      escaped leaflets.

PMID- 8149279
TI  - Pulmonary edema of the right upper lobe associated with acute mitral
      regurgitation.
AB  - To determine the association between mitral regurgitation and pulmonary edema
      localized in the right upper lobe, the authors reviewed 21 cases of mitral
      regurgitation secondary to dysfunction or rupture of the papillary muscle or
      rupture of the chordae tendineae cordis. The patients, 12 men and 9 women ranging
      in age from 36 to 92 (mean 64) years, had been admitted to a tertiary care
      hospital between July 1985 and July 1990. Three independent observers, who were
      unaware of the patients' identity or the diagnoses, reviewed the chest
      radiographs. In eight of the patients pulmonary edema was localized
      preferentially in the right upper lobe, an unusual pattern that can simulate
      neoplasia, hemorrhage or infection. All eight patients had myocardial infarction,
      five had papillary muscle dysfunction, and three had rupture of the posterior
      papillary muscle. Mitral regurgitation toward the orifices of the veins of the
      right upper lobe seems to play a role in the preferential distribution of edema
      to that lobe. Awareness of edema in the right upper lobe in association with
      mitral regurgitation might lead to earlier diagnosis of papillary rupture or
      dysfunction and perhaps affect the outcome.

PMID- 8149280
TI  - [Experimental study and clinical use of thin skin flap with subdermal vascular
      rete].
AB  - The extent and limit of defatting and the reliability of the blood supply of
      random-pattern and island flaps with subdermal vascular rete were studied in 12
      piglets. The results showed that if 3 mm of adipose tissue or one third of
      superficial fascia was preserved beneath the subdermal vascular network, the
      survival rate of these two kinds of skin was similar. After division of the
      pedicle on the sixth postoperative day, random-pattern subdermal vascular rete
      skin flap could survive with a length-width ratio of 2.5:1. The area of island
      flap with subdermal vascular rete could be thinned as much as 60%-70%. 27 wounds
      in 25 patients were covered successfully with random-pattern skin flap with
      subdermal vascular rete. In addition, transplantation of 13 free flaps with
      subdermal vascular rete with microsurgical technique was completely successful in
      12 patients.

PMID- 8149281
TI  - [Experimental study and clinical application of restoration of vascularity of
      random thin skin flap with preserved subdermal vascular rete].

PMID- 8149282
TI  - [Reconstruction of the hand with thin skin flap with preserved subdermal vascular
      rete].
AB  - Since Dec. 1991, we have used thin skin flaps to reconstruct hand with scar
      contractures of hand as a result of burn or trauma in 10 patients, including one
      with osteomyelitis of the proximal phalanx. The size of the skin flaps ranged
      from 8-18 x 4 x 7 cm. The shortest time of division of the pedicle was 7 days and
      the longest was 12 days, with a mean of 8. 7 days. The thin skin flap with
      preserved subdermal vascular rete was compared with free skin graft, also with
      preserved subdermal vascular rete, and conventional skin flap, and its advantages
      and shortcomings were discussed. The mechanism of survival after an early
      division of the pedicle was also discussed.

PMID- 8149283
TI  - [Use of paraumbilical perforator artery pedicle flap with preserved subdermal
      vascular network in hand injury].
AB  - From October 1990 to September 1991, 11 cases of hand injury (2 cases of
      infected) had been repaired successfully with paraumbilical perforator artery
      pedicle axial flap with preserved subdermal vascular network. The largest size of
      the flap was 20cm x 6. 5-10. 5cm and the smallest one was 6. 5cm x 2. 5cm. All of
      skin flap survived. Division of the pedicles was performed 5-7 days
      postoperatively except 2 cases with infected wringer injury, which was done on
      9th and 11th day. The pedicle division time and the quality of axial flap with
      preserved subdermal vascular network are discussed.

PMID- 8149284
TI  - [Use of thin skin flap with preserved subdermal vascular rete in the repair of
      electric burn of fingers].

PMID- 8149285
TI  - [Application of pedicled thin skin flap in electric contact burn].
AB  - Eight cases with deep injuries as a result of electric contact burn were repaired
      with 8 pedicled thin skin flap successfully. The area of pedicled thin skin flap
      was from 6cm x 4cm to 12cm x 3cm. The pedicles of the flap were divided on 7-10
      postoperative days after clamp training of the pedicles, and all the flaps
      survived. The cosmetic and functional results were all satisfactory. The
      operative method is described, and the mechanism of skin flap survival is
      discussed.

PMID- 8149286
TI  - [Epidemiological analysis of 9695 cases of electric burns].
AB  - 9695 cases of electric burn patients admitted to 84 hospitals in 26 provinces,
      municipalities and autonomous regions of China were analyzed. Useful
      epidemiological data pertaining to sex and age distribution, profession,
      treatment, amputation rate, survival rate, and complications etc were obtained.

PMID- 8149287
TI  - [Pathological changes in the liver after electric burn in rabbits].

PMID- 8149288
TI  - [Electrocardiographic changes after high-tension electric shock].

PMID- 8149289
TI  - [Squamous cell carcinoma arising from burn scars].
AB  - 37 cases of squamous cell carcinoma (SCC) arising in burn scars were reviewed.
      They were diagnosed between 1963 to 1991, accounting for 9.6% of 387 cases of
      skin SCC diagnosed during the same period. 24 cases were male and 13 female.
      Their ages varied from 15 to 73 years, with a mean age of 43 years. The interval
      period from initial burn to diagnosis of SCC ranged from 12 to 63 years, with a
      mean of 35.7 years. Macroscopically, an infiltrative ulcerative carcinoma was
      found in 12 cases, and an exophytic cauliflower like carcinoma was seen in 25
      cases. Microscopically, the SCC was well differentiated in 26 cases, moderately
      differentiated in 8 cases, poorly differentiated in 3 cases. The course of growth
      of the malignancy, the clinicopathological features and the clinical diagnosis
      concerning the burn scar carcinoma were discussed in this paper.

PMID- 8149290
TI  - [Skin carcinoma arising from scar (a report of 6 cases)].
AB  - In the past 20 years, we had seen 6 patients of carcinoma arising from scar,
      accounting for 0.78% (6/765) of all inpatients with scars and 17% (6/35) of all
      skin carcinoma patients. The causes were thermal burn, radiation burn and trauma.
      In 2 cases of radiation burn, one was irradiated for the treatment of hairy legs
      with 60Co. The carcinoma was diagnosed 6 years after irradiation, and he died of
      bone sarcoma 12 years after irradiation. In a patient, X-ray irradiation was
      given for keratosis of the palm, and scar carcinoma of palm developed 22 years
      after radiation. Scar carcinoma is a highly differentiated squamous cell
      carcinoma in most of the cases. Because of scar fibrosis and thrombosis of blood
      vessel and lymphatic vessel, the growth of scar carcinoma is slow. The metastasis
      is restricted. If the carcinoma can be diagnosed and treated early, the prognosis
      is favorable. The principle of operation is wide excision of the lesion. In some
      cases amputation is a safe but radical surgery.

PMID- 8149291
TI  - [Clinical application of the fascia lata flap].
AB  - The clinical application of the musculo-cutaneous flap of musculus tensor fascia
      lata has been limited because it includes muscle and it is very thick. To correct
      this disadvantage, the ascending branch of the lateral femoral circumflex artery,
      which is the supplying artery, is dissected up to its entrance into the tensor
      muscle of the fascia lata, then the upper, middle and lower branches were
      identified, and the upper and middle branches are ligated, followed by resection
      of the muscle, resulting in a fascia lata flap supplied by the lower branch only.
      The flap contains the lateral femoral cutaneous nerve. It is a good flap to
      repair a defect of skin and to restore sensory function at the same time. It has
      been used in 15 cases with good effect.

PMID- 8149292
TI  - [Bi-dimensional staged excision].

PMID- 8149293
TI  - [Correlation of examination with nasal tone meter and evaluation in patients with
      cleft palate].

PMID- 8149294
TI  - [Prethrombotic state in burn patients].
AB  - 78 burned patients (53 males and 25 females) were classified into 4 groups (mild:
      14 cases, moderate: 13 cases, severe: 17 cases and extra--severe: 34 cases) in
      accordance with criteria established by the Chinese Society for Burns. 22
      parameters related to platelet, coagulant and anticoagulant factors, fibrinolysis
      system and hemorheology were determined in the first 24 hours, and on the third
      and fifth post burn days. The results were as follows: Fibrinogen antigen, von
      Willebrand factor antigen, plasminogen activator inhibitor activity, thromboxane
      B2 and hematocrit and whole blood viscosity significantly increased, while
      antithrombin III, protein C antigen, free protein S and 6-Keto-prostaglandin F1
      alpha markedly decreased as compared with normal control in the first 24 hours
      postburn. In addition, fibrinogen antigen, von Willebrand factor antigen,
      plasminogen inhibitor activity, thromboxane B2 and whole blood viscosity were
      persistently elevated, while antithrombin III, protein C, free protein S and 6
      Keto-prostaglandin F1 alpha declined on the third and fifth postburn days. These
      changes resulted in a prethrombotic state, which might be an important factor in
      the pathogenesis of microthrombosis in burn sites, resulting in deepening of burn
      wound on the third and fifth days in burn patients.

PMID- 8149295
TI  - [Index for deep burn injuries: (2). Analysis of 117 cases].
AB  - A trial to index for deep burn injuries (IDBI) on the basis of 304 burn sites in
      117 patients was reported in this paper. Based on the index, a gradation of IDBI
      from Type I to Type V was developed. Further analysis of the 117 cases suggested
      that the IDBI might provide a reliable numerical indication system for the early
      diagnosis, guide for repair, prognosis as well as further study in the field of
      the deep burn injuries.

PMID- 8149296
TI  - [Advances in the experimental study and clinical uses of venous transplantation].

PMID- 8149297
TI  - Health Level Seven (HL7): standard for healthcare electronic data transmissions.
AB  - The nursing profession needs computer-formatted data that can be exchanged within
      and between agencies. The exchange of electronic data, both in the United States
      and in the international community, requires agreement on the format of the data
      elements to be exchanged. The Health Level Seven (HL7) standard is a proposed
      voluntary standard for healthcare applications that addresses the way information
      is exchanged electronically. This brief article will provide background
      information regarding the development and status of HL7 and its implications for
      nursing. From the clinical perspective, nurses follow standards of care developed
      by professional organizations. These standards facilitate clear communication
      among nurses, consumers, and members of other disciplines. Similarly, the
      electronic transmission and exchange of clinical information must have a standard
      to ensure that messages arrive and are decoded correctly. Many standards for
      electronic data already exist; financial transactions such as banking are
      familiar examples. The theme of the 1990 Symposium on Computer Applications in
      Medical Care (SCAMC), was Standards in Medical Informatics. Many pertinent papers
      and workshops were presented. However, references to electronic data standards
      are found primarily in conference proceedings and technical manuals. Thus,
      although activity is widespread, and events are rapidly moving in the healthcare
      industry, most of the information is not yet widely available. It seems timely,
      therefore, to provide background material to nurses in order for them to
      participate in the process.

PMID- 8149298
TI  - HyperDesigning: an instructional design model applied to the development of a
      HyperCard computer assisted instruction on intramuscular injection sites.
AB  - As more instructional software is designed by faculty, it becomes increasingly
      important, as well as time efficient, that faculty approach development of
      software from an instructional design perspective. Today, faculty can select
      among emerging technologies, and the future will undoubtedly present even more
      options. Educators who want to design their own computer assisted instruction
      (CAI) programs are frequently left to their own devices for instructional design.
      Instructional design models can provide helpful guidelines for selection and
      development of relevant programs. This article outlines the development of a
      faculty-designed software program using the Seels and Glasgow model of
      instructional design. The Seels and Glasgow model employs the essential
      components of analysis, design, development, implementation, evaluation, and
      diffusion with iterative intermediary steps.

PMID- 8149299
TI  - A study of the paper chart and its potential for computerization.
AB  - The traditional paper chart is an expensive and inefficient method of managing
      the mountains of information gathered about each patient admitted to the
      hospital. Greater efficiency can be obtained through the use of computerized
      systems of documentation that facilitate the rapid processing of information and
      make that information immediately available to care providers. A systematic
      analysis of the medical record at the Medical Center at Princeton provided
      valuable information to determine the outcome potential of a computerized
      documentation system.

PMID- 8149300
TI  - Design and development of an expert system for student use in a school of
      nursing.
AB  - Use of the expert system as a tool for clinical decision support for students and
      practitioners of nursing is a subject of much discussion and developmental
      activity. A prototype of a nursing expert system was designed for use in a
      simulated laboratory environment to provide nursing students with decision
      support in identifying and managing common postoperative complications. Formative
      evaluation of the system with associate and baccalaureate nursing students
      elicited positive response and formed the basis for ongoing program refinement.
      The practicing nurse of the future must understand expert system use in order to
      consider the implications and potential of such a clinical tool in nursing
      practice.

PMID- 8149301
TI  - Expert systems as computer assisted instruction systems for nursing education and
      training.
AB  - The ever-increasing specialization of nursing care may require nursing
      professionals to provide nursing care outside of their specialty. Nurses will
      have to familiarize themselves with a new specialization area at short notice.
      Fortunately, expert-systems technology can prove particularly helpful in
      achieving this familiarity. As such, this technology can prove a valuable tool
      for education and training of nursing professionals and students. This article
      describes the unique edge that expert systems technology provides in this
      context. Using VP-Expert, an expert system shell, the authors present two
      examples to illustrate the development of a computer aided instruction system and
      the unique benefits such a system offers.

PMID- 8149302
TI  - Repurposing videodiscs for interactive video instruction: teaching concepts of
      quality improvement.
AB  - The purpose of this study was to develop an interactive video instruction (IVI)
      program to teach registered nurses in the clinical setting concepts of quality
      improvement and to test the effectiveness of the program. The Smith Author System
      was used to combine text and video sequences repurposed from videodiscs developed
      for nursing education to describe and illustrate concepts of quality improvement.
      A sample of 55 registered nurses from a midwest regional medical center who used
      the program had a significant increase in knowledge (p < .05) from pre- to
      postprogram opinionnaire. More nurses with baccalaureate degrees scored above the
      median for the interactive video instruction program than those with associate
      degrees or diplomas. Registered nurses with more than 5 years of experience also
      expressed willingness to apply the concepts of quality improvement to their daily
      patient care activities and to use computers for learning.

PMID- 8149303
TI  - Self-instructional laboratories revisited by high technology.
AB  - Faculty at Southeastern Louisiana University School of Nursing identified a need
      to change the method of teaching basic nursing skills. A creative approach was
      needed to handle the increasing number of students without compromising the
      learning experience. The out-dated media center was renovated into a computer
      laboratory. Self-instructional modules to teach skills were developed using
      interactive video technology, computer assisted instruction, and videocassettes.
      The change was a success.

PMID- 8149304
TI  - Point-of-care technology: the 'window' into the integrated clinical database,
      Part 7.

PMID- 8149305
TI  - A comparative assessment of interactive videodisc instruction.

PMID- 8149306
TI  - International file: the finer points of working in England's ORs.
AB  - The fundamental philosophy behind quality patient care is international; the
      specialised area of OR nursing should be less susceptible to international
      differences. Yet, the experience of moving to a different country reveals the
      extent of the actual cultural and professional variations available. The subtle,
      yet real, practical differences observed by a Canadian OR nurse, after working in
      England for two years, are examined.

PMID- 8149307
TI  - The contoured anterior spinal plate: a nursing perspective.

PMID- 8149308
TI  - President's message: motivation/behaviour.

PMID- 8149309
TI  - The ABC's of recovery room nursing.

PMID- 8149310
TI  - Biochemical and physiological characteristics of Yarrowia lipolytica strains in
      relation to isolation source.
AB  - The physiological characteristics and fatty acid composition of 40 strains of
      Yarrowia lipolytica isolated from irradiated poultry meat, commercial chilled
      foods, the superficial water of lagoons of an Italian river delta, and commercial
      light butter were compared. Discriminant analysis of the results permitted the 40
      strains to be classified into four groups according to their isolation source.
      The lag phase length at 3, 5, and 7 degrees C, the proteolytic and lipolytic
      activities, and the growth on sorbitol, gluconate, and N-acetylglucosamine, as
      well as the relative percentages of C12:0, C15:0, C17:1, C18:1, C18:2, the
      unsaturation level, and the percentage of total odd chain fatty acids were the
      characteristics exhibiting the highest discriminatory power. These results
      indicate that the isolates are well adapted and significant biochemical
      characteristics may account for the success of individual strains in their
      original habitat.

PMID- 8149311
TI  - PID, a new member of the P1 bacteriophage group.
AB  - Phage P1D produces particles of essentially uniform head size and differs from P1
      in its range and tail length. The dimensions of phage P1 are reassessed. The P1
      phage group shows signs of morphological evolution.

PMID- 8149312
TI  - Adherence of Candida albicans germ tubes to murine tissues in an ex vivo assay.
AB  - Adhesion of Candida albicans germ tubes to murine tissues was examined. An ex
      vivo assay previously employed to examine adhesion of yeast cells of C. albicans
      was adapted for use with germ tubes. Binding of germ tubes to kidney, liver,
      spleen, and lymph node tissues was found to occur throughout the tissue section,
      with little morphologic specificity. In general, more organisms adhered to spleen
      and lymph node tissues than to kidney and liver tissues. Observation of adhesion
      with scanning organisms adhered to spleen and lymph node tissues than to kidney
      and liver tissues. Observation of adhesion with scanning electron microscopy
      showed three germ tube-tissue interactions described as loose, tight, or
      embedded.

PMID- 8149313
TI  - Attempted suicide using insulin by a non diabetic: a case study demonstrating the
      acute and chronic consequences of profound hypoglycemia.
AB  - This paper describes the case of a non diabetic physician with a prior
      psychiatric history in which there was overwhelming biochemical and clinical
      evidence that he had attempted suicide by injecting himself with an overdose of
      insulin. He was extensively monitored from the time of his admission to hospital
      in a coma, until he fully recovered consciousness 30 days later and during the
      next eight months of his rehabilitation. This case attests to the high level of
      morbidity which might follow profound hypoglycemia. It also illustrates some
      putative psychodynamics of suicidal behaviour--notably ambivalence and denial (at
      the time of writing, the patient never acknowledged that he had overdosed with
      insulin). A selective review on some of the more recent literature on the
      neuropathological effects of insulin overdose and profound hypoglycemia is
      presented.

PMID- 8149314
TI  - Capacity to stand trial: pitfalls of legal interpretation.
AB  - Legally, the concept of fitness to stand trial is fixed and absolute.
      Psychiatrists view fitness as a homeostatic functional capacity. The Ontario
      Court of Appeal recently set a precedent (Queen versus Taylor) for a standard of
      fitness to stand trial by interpreting the criteria for unfitness as defined in
      terms of Section 2 of the Criminal Code. They held that only a factual
      understanding of these criteria is required by the courts. A person suffering
      from acute psychotic symptoms with delusions which relate to the subject matter
      of the trial, who act contrary to their best interests and who are disruptive in
      their behaviour to the orderly flow of the trial may still fulfill the criteria
      for fitness to stand trial. The writer illustrates some important implications of
      this decision and suggests recommendations to current legal interpretations of a
      clinical capacity.

PMID- 8149315
TI  - Case report of a person with Down's syndrome and multiple personality disorder.
AB  - A case is presented of an individual with Down's syndrome and multiple
      personality disorder. No such cases were found in a review of the literature.
      Three other individuals with Down's syndrome are also discussed whose symptoms
      range from experiencing imaginary friends to experiencing borderline multiple
      personality disorder. In all these cases the imaginary friends became more
      evident and resistive of diversion as the levels of stress increased. We
      speculate that experiencing imaginary friends progresses to experiencing multiple
      personality disorder in some individuals as personal stress increases. These
      cases also indicate that limited cognitive development does not preclude
      individuals from presenting with imaginary friends or multiple personality
      disorder.

PMID- 8149316
TI  - Co-existence of misidentification, pseudocyesis and erotomanic delusions.

PMID- 8149317
TI  - Sustained bradycardia during fluvoxamine and buspirone intoxication.

PMID- 8149318
TI  - Necrotizing enterocolitis in a newborn: maternal psychotropic drugs suspected.

PMID- 8149319
TI  - Etizolam for auditory hallucinations in schizophrenia.

PMID- 8149320
TI  - [Clozapine and priapism: an association to consider].

PMID- 8149321
TI  - Teaching psychiatry in Cuba.

PMID- 8149322
TI  - Toward a consensus: the synthesizing formulation.

PMID- 8149323
TI  - [Some consequences of catchment area psychiatry: a stand against sectorization].
AB  - The author presents a critical and polemic essay bearing on the organization of
      psychiatric services based on catchment areas. Several negative consequences are
      discussed: the loss of initial goals related to community psychiatry, the
      adoption of a major first-line role for psychiatrists and the identification of
      psychiatrists to the treatment of chronic and severe psychiatric disorders.
      Catchment area psychiatrists and psychiatric teams frequently function in a
      unique manner within the medical profession, and their spreading throughout the
      community leads to the development of closed subcultures often characterized by
      resistance to change and a lack of academic motivation. Catchment area psychiatry
      is also described as generating crisis after crisis and as detrimental to the
      positive evolution of former mental hospitals.

PMID- 8149324
TI  - Mood swings in patients with panic disorder.
AB  - Depression is frequently found in patients with panic disorder. It is known that
      patients suffering from panic disorder and depression have more severe symptoms
      of anxiety and avoidance and respond less well to treatment with antidepressants.
      The General Behaviour Inventory, an instrument that identifies subjects with
      subsyndromal and syndromal recurrent mood disorders was completed by 108 patients
      in a panic disorder program. Thirty-four percent (n = 37) were classified as
      suffering from a mood disorder. Of the mood disordered patients, 25 of 37 (68%)
      (23% of the total) were classified as suffering from bipolar or cyclothymic mood
      disorder.

PMID- 8149326
TI  - Heterogeneity of rat aortic smooth muscle cell replication during development:
      correlation with replicative activity after experimental endothelial denudation
      in adults.
AB  - Proliferation of smooth muscle cells (SMCs) is a major event in vascular
      development and atheromatous plaque formation. In order to characterize SMC
      replicative potential, newborn rats have been injected with 3H-thymidine (3H-TdR)
      during their first week of life when most of SMCs were proliferating; then, 3H
      TdR labelling was evaluated in adult rats. Depending on the number of mitosis
      that SMCs had accomplished after the first week of life, four different SMC
      subpopulations could be defined indicating that rat aortic SMCs are heterogeneous
      in their replicative activity. 5-Bromo-2'-deoxyuridine (BrdU) incorporation after
      balloon induced endothelial denudation of rat aorta in adult rats showed that
      SMCs entering into the cell cycle were mainly devoid of 3H-TdR labelling. This
      category could derive from two distinct SMC subpopulations: SMCs which were
      arrested in their proliferation before or just after birth or SMCs which had
      actively replicated during development. Thus, one (or two) subpopulation(s) of
      rat aortic SMCs, characterized by a particular replicative activity during
      development, is (are) selectively activated after balloon induced endothelial
      denudation.

PMID- 8149325
TI  - A thirty-year retrospective study of hospitalization among severely mentally ill
      patients.
AB  - This study examines the effects of deinstitutionalization policies on psychiatric
      hospitalization rates over a thirty-year period. It is based on a retrospective
      study of successive hospitalizations in severely disabled patients. The data
      indicate that in any five-year period these patients still spend over 20% of
      their time in hospital. For patients who have stayed for a total of more than one
      year every five years in hospital, the average length of stay has been decreasing
      far less rapidly in the last fifteen years than it had previously. Patients who
      were first admitted after 1971 spent proportionally as much time in hospital as
      those whose first stay was earlier. These results show that the groups primarily
      affected by deinstitutionalization are those who were first hospitalized prior to
      the 1970s and those who are the heaviest hospital users. However, the data from
      the patients admitted since the seventies seem to reveal that the process of
      change may have reached its limits.

PMID- 8149327
TI  - Orthogonal arrays of particles (OAPs) in perivascular astrocytes and tight
      junctions in endothelial cells. A comparative study in developing and adult brain
      microvessels.
AB  - The plasmamembranes of the astrocyte processes, which envelop the capillaries of
      the adult brain, contributing to the blood-brain barrier constitution, are
      characterized by peculiar aggregates of intramembrane particles (IMPs) packed in
      orthogonal arrays (orthogonal arrays of particles, OAPs). With the aim of
      investigating the maturation sequence of the cerebral microvasculature, the IMPs
      distribution has been analysed in the plasmamembranes of both perivascular
      astrocytes and endothelial cells of fractured microvessels, in 16-, 20-, 21-day
      chick embryo and 10-day chicken optic tecta. The IMPs distribution undergoes
      remarkable changes from late embryonic to early postnatal life in the astrocytes
      and endothelial cells as well. In the astrocyte plasmamembranes, short chains of
      individual particles and linear units of packed ones precede the appearance of
      complete OAPs; in the endothelium junctional plasmamembranes, fibrils of fused
      particles precede the formation of fibrillary networks which express the tight
      junction setting up. The parallel formation of the astrocytic OAPs and the
      endothelial tight junctions further supports the suggestion that mutual
      relationships establish between perivascular glia and endothelium in the cerebral
      microvasculature differentiation during the blood-brain barrier development.

PMID- 8149328
TI  - Ultrastructure of macrophages and dendritic cells in osteopetrosis (op) mutant
      mice lacking macrophage colony-stimulating factor (M-CSF/CSF-1) activity.
AB  - The ultrastructural features of macrophages and dendritic cells of mice
      homozygous for osteopetrosis (op/op) mutation were studied. The mutant mice are
      characterized by defective differentiation of osteoclasts, monocytes, and tissue
      macrophages due to the lack of functional macrophage colony stimulating factor (M
      CSF/CSF-1) activity. In op/op mice, tissue macrophages were reduced in number and
      smaller than in normal littermates. Macrophages in op/op mice showed various
      degrees of phagocytosis but the development of intracytoplasmic organelles and
      microvillous projections was poor. After administration of CSF-1 daily for 2
      weeks, macrophages in op/op mice developed lysosomes and microvillous
      projections. In the thymic medulla, T-cell zone of lymph nodes, splenic white
      pulp and epidermis of the op/op mice, the number of dendritic cells was similar
      to that in normal littermates and the dendritic cells developed a tubulovesicular
      system typical of interdigitating cells. Birbeck granules in epidermal Langerhans
      cells were detected in unmanipulated op/op mice, op/op mice injected with CSF-1,
      and normal littermates or control mice. However, in untreated op/op mice,
      dendritic cells projected shorter cytoplasmic processes than in normal
      littermates, normal control mice and CSF-1 injected op/op mice. These results
      indicate that the differentiation and maturation of tissue macrophages are
      mediated by CSF-1, but the dendritic cell differentiation is controlled by other
      factor(s) than CSF-1, most probably by GM-CSF.

PMID- 8149329
TI  - The nature of anionic sites and the endocytic pathway in heart muscle cells.
AB  - The distribution and internalization of anionic sites in heart muscle cells (HMC)
      were studied by direct measurements of their zeta potential (ZP) and by
      ultrastructural cytochemistry. Our data showed that HMC are negatively charged
      and that their anionic sites are distributed over the entire sarcolemma.
      Treatments with neuraminidase and trypsin altered the ZP value and also reduced
      binding of cationized ferritin (CF) to the sarcolemma. Sialic acid was shown to
      be an important component on the surface of HMC, since its removal reduced the
      cell surface negative charge by 25%. Phospholipase C did not significantly change
      the surface charge, nor did it alter HMC reactivity to CF particles when compared
      with control cells. Endocytosis of anionic sites was investigated using two
      different protocols that allow follow-up of this dynamic process. Incubation of
      HMC with cationized ferritin particles at 37 degrees C induced a redistribution
      of ligand-bound anionic sites, followed by their internalization or detachment.
      The clustering of anionic sites on the surface of HMC indicates that these cells
      are characterized by a high level of membrane fluidity. CF particles were
      localized inside early and late endosomes, lysosomes, and also in ferritin
      enriched vesicles near the sarcolemma. An endocytic pathway for anionic sites in
      HMC is discussed.

PMID- 8149330
TI  - Transmission electron microscope study of human hydrocephalic cerebral cortex.
AB  - Cortical biopsies of 17 patients with diagnosis of hydrocephalus and associated
      pathology were examined under the transmission electron microscope to study
      alterations of neurons, neuroglial cells, extracellular space and capillary wall.
      Nerve cells showed moderate and severe swelling as well as dilation of
      endoplasmic reticulum canaliculi and perinuclear cistern, edema and degenerative
      changes of Golgi apparatus, variable degrees of mitochondrial swelling and
      fragmentation of plasma membrane. The neighbouring neuropil showed notable
      enlargement of extracellular space and signs of synaptic degeneration
      characterized by swollen pre- and postsynaptic endings, clumping of spheroidal
      synaptic vesicles and detachment of glial synaptic ensheathment. The astrocytes
      exhibited edematous changes and phagocytic activity. Oligodendroglial cells
      appeared normal in certain cases and in others showed moderate hydropic changes.
      Evidences of oligodendrocyte mitotic divisions were not found. Numerous myelin
      figures were observed in some undifferentiated nerve cells. The capillary wall
      showed evident signs of blood-brain barrier dysfunction featured by increased
      endothelial vesicular and vacuolar transport, open interendothelial junctions and
      focal capillary basement membrane thickenings.

PMID- 8149331
TI  - Actinobacillus pleuropneumoniae in gnotobiotic piglets: ultrastructural changes
      in the pulmonary alveoli with dose and time.
AB  - The ultrastructural changes in pulmonary alveoli produced by transtracheal
      inoculation of 10(6) and 10(8) CFU of Actinobacillus pleuropneumoniae serotype 5
      in gnotobiotic piglets were studied after 1 and 4 h. At 1 h postinoculation
      (p.i.) with 10(6) or 10(8) CFU, no gross change in lung and no evidence of
      infiltration of cells into alveoli was observed. At 4 h p.i., at a dose of 10(6)
      CFU, a generalized red mottling occurred in the dorsal half of the caudal lobe,
      which revealed ultrastructural evidence of neutrophil infiltration into alveoli
      along with fibrin and a few erythrocytes. At 4 h p.i., at a dose of 10(8) CFU,
      there was a bilateral lung lesion characterized by a generalized mottling and
      congestion, within which we observed ultrastructural evidence of bacteria and
      cellular debris in the alveoli and fibrin clots and cellular necrosis in the
      alveolar septum. By using gnotobiotic piglets and visualizing the effects of
      bacterial inoculum on cellular ultrastructure of the lung, we have demonstrated
      that both dose and time play roles in the early pathogenesis of experimental
      porcine pleuropneumonia. The developing lesion in lungs of gnotobiotic piglets
      infected with pure cultures of A. pleuropneumoniae can be controlled
      experimentally. This experimental procedure can provide a base of reproducible,
      sequential, ultrastructural changes with which to compare the role of
      inflammatory mediators in the lung and the effects of drugs on immunologic events
      in the lung.

PMID- 8149332
TI  - Morphometric analysis of renal proximal tubules in cadmium-treated rats.
AB  - The morphological changes in renal proximal tubules of Sprague Dawley rats given
      acute or chronic exposure to cadmium were analysed. Cadmium chloride was
      administered either by five subcutaneous injections of cadmium at 2 mg kg-1 body
      weight or in drinking water at 100 micrograms ml-1 for 39 weeks. The mean cadmium
      concentration in the kidneys of these rats was 45 and 102 micrograms g-1 wet
      weight respectively. The rats were anaesthetized and the kidneys were fixed by
      perfusion and processed for electron microscopy. Proximal tubule profiles were
      larger in the acute exposure rats. The brush border in both groups of treated
      rats was shorter and there were focal areas of loss of microvilli. The surface
      density of microvillus membrane per unit cell volume was reduced by 25% and 19%
      for chronic and acute dosed rats respectively. There were few significant changes
      in organelles detected by morphometric analysis of the entire kidney tissue,
      however there was a reduction in volume density of lysosomes following chronic
      exposure and individual necrotic cells and distorted nuclei were observed. The
      morphological changes observed in chronic and acute dosed rats were consistent
      with a primary site of toxic insult on the apical plasma membrane. There appeared
      to be no evidence for change in fluid and electrolyte homeostasis in the
      epithelium. The results suggest that the cadmium may produce a selective deficit
      of transport mechanisms for macromolecules.

PMID- 8149333
TI  - X-ray microanalysis of renal proximal tubules in cadmium-treated rats.
AB  - Cadmium chloride was administered to Sprague-Dawley rats in drinking water at 100
      ppm for 39 weeks. The mean cadmium concentration in kidneys from 5 rats at the
      end of this period was 102 +/- 17 micrograms g-1 wet weight (mean +/- SE)
      compared with 0.22 +/- 0.15 microgram g-1 wet weight in a similar group of
      control rats. Right kidneys were rapidly frozen in propane and small pieces of
      cortex were prepared for X-ray microanalysis by freeze-substitution in
      ether/acrolein for 21 days. Analysis of freeze-substituted sections showed that
      Cd concentrations rose to 3.9 mmol kg-1 of resin embedded tissue (approximately
      wet weight) in cytoplasm and 6.5 mmol kg-1 in nuclei. At the same time S
      concentrations rose by 31 percent in nuclei and 23 percent in the cytoplasm. Cd
      was also present in lysosomes. Cytoplasmic and nuclear ionic (Na, K, Cl, Ca, Mg)
      concentrations did not change in spite of a considerable decrease in microvillus
      membrane surface area. The concentration of P also did not change suggesting that
      nucleoside phosphate levels remained stable. The distribution of Cd and S
      supports current concepts of cadmium toxicity. Although total kidney Cd was at
      the critical concentration and extensive damage to microvilli had occurred, there
      appeared to be no effect on ionic permeability and cell electrolyte balance and,
      by inference, NaCl reabsorption.

PMID- 8149334
TI  - Ultrastructure of human liver grafts preserved with UW solution. Comparison
      between patients with low and high postoperative transaminases levels.
AB  - We studied the morphology of sinusoidal cells on 21 human liver grafts prior to
      harvesting, at the end of the preservation period in UW solution, and after
      complete revascularization. The mean cold ischemic period was 11 h 34 min.
      Immediate follow-up was uneventful in 20 of these cases; 13 showed a mean peak of
      postoperative transaminases below 1,300 IU/L (group A), and 7 above 1,500 IU/L
      (group B). In the case of one patient (group C) steatosis was severe (50%) and
      there was serious postoperative dysfunction (transaminases 18,000 IU/L). Biopsies
      were perfusion-fixed by the transparenchymal route to ensure satisfactory
      ultrastructural results. In group A, some sinusoidal endothelial cells presented
      signs of activation at the end of the preservation period, and even more after
      revascularization. Kupffer cells also presented signs of activation particularly
      after reperfusion. Signs of endothelial cell damage with gaps and partial rupture
      of the plasmic membrane were also observed, particularly after revascularization
      in areas which contained numerous inflammatory cells adhering to the wall. The
      sinusoidal pole of hepatocytes was occasionally damaged, with the formation of
      blebs. In group B, adhesion of inflammatory cells to the sinusoidal wall was
      increased. Furthermore, in some areas with endothelial cell damage, neutrophils
      and platelets infiltrated the Disse space, and hepatocytes were increasingly
      damaged. In the case of patient C, the most obvious signs after reperfusion were
      hepatocyte drop out and death but there was no evidence of any concomitant
      sinusoidal cell damage. It would appear that even in cases where immediate follow
      up is eventful, endothelial and Kupffer cells show signs of activation. This can
      be associated with signs of microcirculatory disturbances as was seen in 4 cases
      in group B. In the only case of severe steatosis that we studied, the essential
      sign was death of hepatocytes.

PMID- 8149335
TI  - Abnormal length of respiratory cilia in a pig. An ultrastructural study.
AB  - The authors report the first case of abnormal length of respiratory cilia in a
      domestic animal (18 microns versus normal length about 5 microns). These cilia
      lie on the carpet of cilia of normal length. The width of some of these cilia is
      also abnormal, measuring 0.5-0.6 microns. Other cilia have hook-shaped tips that
      could be responsible for an effective beat. We suggest that the ineffective
      ciliary beat could also be due to the undulating movements of abnormally long
      cilia, and stress the need for further morphological and biochemical studies of
      respiratory cilia in pigs. Respiratory pathology is a very common finding in pigs
      and is responsible for remarkable economical losses.

PMID- 8149336
TI  - Functions of the Golgi complex in cell division: formation of cell-matrix
      contacts and cell-cell communication channels in the terminal phase of
      cytokinesis.
AB  - The Golgi complex of mammalian cells is disorganized into dispersed vesicular and
      tubular elements during mitosis and is then reorganized into an interconnected
      system of cisternal stacks in each daughter cell during cytokinesis. Recent
      studies further indicate that the Golgi complex is typically relocated from the
      proximal to the distal side of the nucleus in the terminal phase of cytokinesis
      (as related to the intercellular bridge). Here, the functional role of this shift
      in position was approached using rat embryo fibroblasts synchronized with
      thymidine and nocodazole. Mitotic cells were collected by shaking and seeded in
      medium without or with brefeldin A (a fungal metabolite that inhibits protein
      secretion). They were fixed after one or two hours and stained for
      immunocytochemical demonstration of mannosidase II (a Golgi protein), fibronectin
      (an extracellular matrix protein), the fibronectin receptor (a member of the
      integrin family of proteins), and connexin 43 (a member of the connexin family of
      gap junction proteins). One hour after seeding, the cells had completed mitosis
      and progressed into cytokinesis. The Golgi complex was now usually located on the
      proximal side of the nucleus and overlapping fibrillar arrays of fibronectin and
      fibronectin receptors were observed in the contact zone between the daughter
      cells, while connexin 43 mainly occurred in fine dispersed spots. Two hours after
      seeding, the cells had spread out on the substrate and started to move apart. The
      Golgi complex was now usually located on the distal side of the nucleus.
      Moreover, fibronectin and fibronectin receptors were found to codistribute both
      in the contact zone between the daughter cells and in adhesive contacts beneath
      them, while connexin 43 was concentrated to plaques in the former zone. After
      treatment with brefeldin A, there was a diffuse cytoplasmic staining for
      mannosidase II and fibronectin and no distinct extracellular staining for
      fibronectin was noted. In addition, the connexin 43 positive plaques were reduced
      in size and number. Although the cells completed cytokinesis in the presence of
      the drug, they showed an increased tendency to detach from the substrate and
      locate on top of each other rather than to move apart normally. Taken together,
      the observations suggest that the change in position of the Golgi complex during
      cytokinesis serves the function to direct transport of secretory proteins as well
      as membrane constituents to different parts of the cell surface at different
      times.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8149337
TI  - Primary cilia in cultured mammalian cells: detection with an antibody against
      detyrosinated alpha-tubulin (ID5) and by electron microscopy.
AB  - A fluorescent-labelled antibody against detyrosinated alpha-tubulin, ID5 (Wehland
      and Weber, 1987), allows primary cilia and centrioles to be detected rapidly and
      accurately for analysis in cell cultures. Many features of primary cilia have
      been re-examined, including frequency of expression in relation to levels of
      confluency, different sera, different cell cycle stages, and following
      trypsinization and centrifugation procedures. The detection of multiple ciliation
      per cell, and the precise positioning of cilia in cells in monolayers are readily
      recorded. The findings are discussed in relation to cilium expression in cell
      growth and cycling, to previous findings based on ultrastructural analysis, and
      to their potential role in sensing the local environment.

PMID- 8149338
TI  - Successful topical treatment of oral lichen planus and leukoplakias with
      fenretinide (4-HPR).
AB  - Eight patients with diffuse (non-operable) pre-cancerous lesions (oral lichen or
      leukoplakias) were treated with fenretinidec (4-HPR) applied topically twice
      daily. After one month of therapy two patients had complete remission and the
      other six had a greater than 75% response. 4-HPR was well tolerated, and no local
      or distant side effects were observed. Topical treatment may be combined with
      oral administration at lower doses to obtain therapeutic results with less
      toxicity than observed with oral administration alone. A study to further
      evaluate the efficacy of topical treatment is in progress at our institute.

PMID- 8149339
TI  - Enhanced growth of mammary adenocarcinoma in rats by chloroquine and quinacrine.
AB  - This study investigated whether the growth of transplanted mammary tumors is
      altered in rats by treatment with the antimalarial drugs chloroquine (CQ) and
      quinacrine (QN). Female inbred F344 rats were divided into three experimental
      groups. Animals were injected i.p. with either CQ, QN or normal saline for 5 days
      a week throughout the entire experimental period (25 days). After 7 days of drug
      treatment each rat received subcutaneously one 2-mm2 aliquot of R3230AC mammary
      adenocarcinoma in the mid-thoracic region. Eighteen days after implantation, all
      rats were sacrificed and tumors were excised, weighed and measured. The results
      indicate that weights and volumes of tumors as well as tumor-to-body weight
      ratios were significantly higher in CQ and QN-treated animals than those in
      saline-treated animals. The final body weights of rats treated with QN were
      significantly lower than those treated with saline. The prostaglandin E2 content
      of tumors was significantly reduced by CQ treatment. Erythrocyte glutathione
      reductase activity coefficient and reduced glutathione concentrations remained
      unaffected by both treatments. These results suggest that CQ and QN have
      significant stimulatory effects on the growth of mammary adenocarcinoma in rats.

PMID- 8149340
TI  - Spermidine acetylation in N1 and N8 position in rat brain and in N-ethyl-N
      nitrosourea-induced gliomas.
AB  - N-ethyl-N-nitrosourea-induced rat gliomas showed a stimulation of cytosolic
      spermidine N-acetyltransferase activity compared with normal brain, with an
      increased formation of N1 and N8-acetylspermidine, suggesting the activation of
      two enzymes acetylating the polyamine in N1 and N8 position, respectively. The
      enhancement in cytosolic spermidine N1-acetyltransferase was probably responsible
      for an activation of the polyamine interconversion pathway in gliomas, as
      indicated by an accumulation of N1-acetylspermidine and a marked increase in
      putrescine. Spermidine N8-acetyltransferase, although acetylating histones at a
      high rate, seemed distinct from the nuclear enzyme, as, unlike from the latter,
      it showed very low affinity for putrescine and was not inhibited by methylglyoxal
      bis(guanylhydrazone).

PMID- 8149341
TI  - Laser scanning microscopic analysis of DNA damage in frozen tissues.
AB  - DNA damage is central to research in many fields, especially cancer research and
      toxicology. The possible loss of DNA structural integrity during freezing or
      sustained maintenance at low temperatures may present difficulties in the
      interpretation of data accumulated in studies of tissues collected over a period
      of time and subsequently evaluated. Using laser scanning microscopic analysis of
      the recently developed single-cell gel (SCG) assay to measure DNA strand breaks
      in individual cells, we found that the basal levels of DNA damage in frozen
      tissue was higher than fresh tissue, but tissues frozen for greater lengths of
      time do not appear to contain significantly more DNA damage than those frozen for
      a short period. Evaluation of DNA damage in tumors stored by or collected using
      cryopreservation may produce artificially exaggerated levels of damage, which
      could limit analytical interpretations.

PMID- 8149342
TI  - A diet containing the lectin phytohaemagglutinin (PHA) slows down the
      proliferation of Krebs II cell tumours in mice.
AB  - Mice injected intraperitoneally with Krebs II cells and then fed on a diet
      containing the lectin phytohaemagglutinin (PHA) developed ascites tumours more
      slowly than mice fed on a control diet. After an 8-day period following injection
      the number of cells recovered from mice maintained on the PHA diet was half that
      from those fed the control diet. A switch of diet from control to PHA on day 4
      after injection resulted in a large decrease in number of tumour cells recovered.
      Mice injected s.c. also developed tumours at later times when fed on the PHA
      diet. A quantitative of ribosomes in polysome-containing fractions showed no
      major differences in protein synthesis in control mice and those fed the PHA
      diet.

PMID- 8149343
TI  - Influences of aging and sex on renal pelvic carcinogenesis by N-butyl-N-(4
      hydroxybutyl)nitrosamine in NON/Shi mice.
AB  - Influences of aging and sex on renal pelvic carcinogenesis induced by N-butyl-N
      (4-hydroxybutyl)nitrosamine (BBN) were examined in 6-, 15 -and 45-week-old male
      and female NON/Shi mice. Histopathological examination revealed an age-related
      shortening of induction time for renal pelvic carcinomas in males, although
      actual incidences did not increase. The histological patterns of carcinomas
      induced in both renal pelvis and urinary bladder demonstrated male mice to be
      more prone to develop transitional cell carcinomas, while squamous cell
      carcinomas were more likely to arise in females. Moreover, the sex factor
      appeared to influence the progression of both renal pelvic and urinary bladder
      carcinomas.

PMID- 8149344
TI  - Alpha 1-antichymotrypsin complexes in human breast cyst fluids.
AB  - Alpha 1-antichymotrypsin, a serum protease inhibitor, was found in 72 breast cyst
      fluids aspirated from women affected by gross cystic breast disease. When
      fractionated by gel chromatography, the presence of protein complexes or
      aggregates was demonstrated. A different distribution of the alpha 1
      antichymotrypsin appeared to be related to the ionic composition of the breast
      cyst fluid; when compared with metabolically active apocrine cysts, a
      statistically significant increase of alpha 1 protease inhibitor values in
      flattened epithelial cysts was revealed (P < 0.001). Two-dimensional
      immunoelectrophoresis showed in apocrine cysts (Na/K ratio < 3) a characteristic
      double peak of alpha 1-antichymotrypsin immunoprecipitin curve. The relationship
      between this alpha 1 protease inhibitor and electrolyte profiles may provide
      further knowledge about the imbalance between proteases and their inhibitors on
      functional changes of gross cysts and might be useful in studies on their
      mechanism of formation and relationship to subsequent breast cancer.

PMID- 8149345
TI  - Lack of promoting activity of 7-methoxy-2-nitro-naphtho-[2,1-b]furan (R7000) in a
      medium-term rat liver bioassay.
AB  - Among the nitro-naphthofurans, 7-methoxy-2-nitro-naphtho[2,1-b]furan (R7000) has
      proved to be a very potent mutagen that causes sarcomas at the subcutaneous
      injection site and carcinomas in the forestomach after p.o. administration. In
      the present study, possible promoting activity for diethylnitrosamine (200 mg/kg,
      i.p.)-initiated liver carcinogenesis was assessed in rats. R7000 dissolved in 5%
      ethanol solution at doses of 10 or 50 mg/l given as the drinking water for 6
      weeks did not enhance development of pre-neoplastic glutathione S-transferase
      placental form positive foci. Thus, it was concluded that R7000 may not be
      carcinogenic for the rat liver under the present experimental conditions.

PMID- 8149346
TI  - Expression of plasminogen activator inhibitor type 1 (PAI-1) by HT-29di human
      large bowel carcinoma cells is modulated as a function of epithelial
      differentiation.
AB  - Highly differentiated epithelial populations (36% mucin-producing cells; sixfold
      increase in alkaline phosphatase activity; development of flat, substrate
      adherent, entero-cytic foci) were induced upon in vitro exposure of HT-29di human
      colon carcinoma cells to sodium butyrate (NaB). 1,25-dihydroxyvitamin D3 [1,25
      (OH)2D3] (10(-7) M) and the ionophore A23187 (0.5 microM) significantly augmented
      (two to threefold) NaB-induced HT-29di differentiation, whereas 1,25-(OH)2D3 or
      A23187 alone were not effective. Induction reflected specific changes in protein
      abundance, involving, most notably, a differentiation-associated increase in the
      expression and substrate-deposition of a 47-kDa protein with pI/mw two
      dimensional map coordinates and immunochemical properties identical to that of
      plasminogen activator inhibitor type 1 (PAI-1), a major regulator of the
      pericellular proteolytic cascade. Culture of HT-29di cells in medium of either
      high (2.5 mM) or low (0.25 mM) Ca2+ concentration did not affect the incidence of
      'spontaneous' differentiation, although NaB-induced goblet cell and enterocytic
      maturation was Ca(2+)-dependent. The inability of 1,25-(OH)2D3, A23187 or
      modulated Ca2+ levels alone (i.e., in the absence of NaB) to effect
      differentiation of HT-29di cells and the Ca(2+)-dependence of the NaB response
      indicate that NaB and Ca2+ act co-operatively to induce colonic epithelial
      maturation in vitro.

PMID- 8149347
TI  - Monoamine oxidase B inhibitor enhances experimental carcinogenesis in rat colon
      induced by azoxymethane.
AB  - The effects of prolonged administration of the monoamine oxidase (MAO)-A
      inhibitor N-methyl-N-propargyl-3-(2,4-dichlorophenoxy)propylamine (clorgyline)
      and the MAO-B inhibitor N-methyl-N-2-propynyl-benzylamine (pargyline) on the
      incidence, number and histology of colon tumors induced by azoxymethane (AOM),
      and on the norepinephrine (NE) concentration in the colon wall and the labeling
      index of colon mucosa were investigated in Wistar rats. Rats were treated s.c.
      with 7.4 mg/kg body weight of AOM once a week for 10 weeks, and also s.c. with 5
      mg/kg body weight of clorgyline or 50 mg/kg body weight of pargyline in 0.9% NaCl
      until the end of the experiment. Treatment with pargyline significantly increased
      the incidence of colon tumors in week 35. However, it did not influence the
      histological appearance of the colon tumors or the histological types and depth
      of involvement of colon adenocarcinomas. Furthermore, it significantly increased
      the NE concentration in the colon wall and the labeling index of the colon mucosa
      during and after AOM-treatment. In contrast, clorgyline had no influence on the
      development or histological appearance of colon tumors. These findings indicate
      that the MAO-B inhibitor, but not the MAO-A inhibitor, enhanced colon
      carcinogenesis, and that its effect may be related to its effect in increasing
      the NE concentration in the colon wall and subsequently increasing the
      proliferation of colon epithelial cells.

PMID- 8149348
TI  - Inhibition of ubiquinone and cholesterol synthesis by the monoterpene perillyl
      alcohol.
AB  - Monoterpenes such as perillyl alcohol have been shown to cause the complete
      regression of advanced mammary carcinomas. Given the common origin of plant
      monoterpenes and many important molecules in mammalian mevalonate metabolism
      pathway, we investigated the effects of the monoterpene perillyl alcohol on
      mevalonate metabolism. NIH3T3 cells were labeled with [14C]mevalonolactone and
      lipids were analyzed. Perillyl alcohol inhibited ubiquinone synthesis and blocked
      the conversion of lathosterol to cholesterol. These two cellular effects of
      perillyl alcohol may contribute to the antitumor activity of the monoterpenes.

PMID- 8149349
TI  - Risk of HTLV-I infection in Japanese women who are last in birth order.
AB  - The percentage of last-born women among pregnant women who were seropositive for
      human T-lymphotropic virus type I (HTLV-I) significantly exceeded that among HTLV
      I seronegative women (119/258 (46.1%): 89/251 (35.4%); P < 0.05). The findings
      suggest that last-born women are susceptible to HTLV-I infection. At least two
      possible interpretations of this birth-order effect are: (i) these last-born
      women were born to mothers who, on the average, were older than those of early
      born women and, as a consequence, were more likely to have been seropositive and
      to have passed on HTLV-I to their daughters; (ii) husband-to-wife transmission of
      HTLV-I requires time to occur, so last-born women are more likely than early-born
      women to become infected.

PMID- 8149350
TI  - Cytostatic and cytotoxic activity of sex steroids against human leukemia cell
      lines.
AB  - We investigated effects of sex steroids and analogs (estradiol, DES, norgestrel,
      progesterone, medroxyprogesterone, and testosterone) on the proliferation and
      survival of 10 human leukemia/lymphoma cell lines (HL-60, K562, U937, CEM, KG-1,
      Jurkat, U266, H929, PA and SUNHL). Micromolar concentrations of sex steroids
      exerted cytostatic and cytotoxic effects on all cell lines tested, irrespective
      of their sensitivity to glucocorticoids. The order of potency of sex hormones
      was: DES > progesterone > or = medroxyprogesterone > testosterone > estradiol >>
      norgestrel. For progesterone and estradiol, cytostatic effects can be achieved at
      lower concentrations than cytotoxic effects. The most potent agent, DES, exerted
      half maximal cytotoxic activity at a median concentration of 4 microM (for 10
      leukemia cell lines). Our results provide a basis for the potential therapeutic
      use of estrogens and progestins in glucocorticoid-resistant leukemias and
      lymphomas.

PMID- 8149352
TI  - Theory as vision: a framework for expressing Christian values in nursing actions.

PMID- 8149351
TI  - High levels of c-myc gene expression precede point mutational activation of Ki
      ras in mouse lung cancer.
AB  - A cell culture model of mouse lung alveologenic carcinoma, consisting of type 2
      pneumocyte-related cells, known to contain an A to G transition in the second
      base position of codon 61 of the c-Ki-ras gene has been examined for molecular
      changes affecting nuclear oncogenes. A small, twofold increase in c-myc mRNA
      levels and transcription levels was observed in malignant cell lines (C4SE9 and
      NULB5) compared with non-malignant cells (C4E10). Interestingly, the
      transcriptional level of the c-myc gene in C4E10 cells was very high relative to
      any other gene examined. Similar high levels of c-myc gene expression levels were
      also observed in type 2 pneumocytes obtained from normal mouse lung tissue. No
      major DNA rearrangements or amplifications were detected between C4E10 cells and
      either C4SE9 or NULB5 cell lines. These data suggest that high levels of c-myc
      gene expression occurred prior to the activating point mutation of the c-Ki-ras
      gene and may predispose the type 2 pneumocyte to transformation.

PMID- 8149353
TI  - A conceptual framework for Christian nursing practice.
AB  - The use of models and theories of nursing has raised questions for Christian
      nurses. It was acknowledge that many of the underlying philosophical assumptions
      made in models and theories of nursing are contrary to those acceptable to
      Christians. Questions of the importance of understanding these philosophical
      assumptions when adopting a model of nursing were raised. What essential
      assumptions should the Christian nurse accept when adopting a given model of
      nursing? Is there in certain circumstances a need to reject a given model of
      nursing because it does not support fundamental Christian beliefs about the
      nature of mankind, society or nursing? Is it necessary for Christian nurses to
      develop their own model of nursing?

PMID- 8149354
TI  - Trends in nursing: yesterday, today and tomorrow.

PMID- 8149355
TI  - Molecular, functional and biochemical characteristics of the dopamine
      transporter: regional differences and clinical relevance.
AB  - The carrier molecule that transports dopamine (DA) across the synaptic membrane
      is known as the dopamine transporter (DAT). Depending on the ionic conditions,
      DAT may function as a mediator of both the inward directed DA transport known as
      the "reuptake" and the outward directed DA transport known as the "release." The
      functional significance of DAT is in the regulation of DA neurotransmission by
      terminating the action of DA in the synapse via reuptake. With use of DAT binding
      as a presynaptic marker to measure altered DA innervation, abnormalities of the
      DAT binding have been demonstrated in idiopathic Parkinson's disease, 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity, and progressive
      supranuclear palsy. Moreover, the identification of DAT as the neuronal element
      that mediates the addictive properties of cocaine highlights its significance in
      cocaine addiction. Cocaine binding in the brain is heterogeneous, and there is an
      uneven distribution of the high- and low-affinity binding sites across the
      anatomical regions. Regional differences in ligand binding are observed by using
      both [3H]cocaine and the diphenyl-substituted piperazine derivatives known as the
      "GBR series" of ligands. The identification of compounds that inhibit the binding
      of medications for cocaine abuse. Furthermore, clarification of the various
      binding domains that may be relevant to transporter function in human
      neuropsychiatric disorders may lead to the development of new medications for
      schizophrenia, Tourette's disease, and drug addiction.

PMID- 8149356
TI  - Ticlopidine: a new antiplatelet agent for the secondary prevention of stroke.
AB  - Ticlopidine hydrochloride, an inhibitor of platelet aggregation that has been
      approved for use in the United States for secondary stroke prevention, may be
      more effective than aspirin for the secondary prevention of stroke, but this
      advantage decreases greatly over time. The pharmacology, adverse effects,
      efficacy, drug interactions, and indications for ticlopidine are discussed here
      with summaries of various clinical trials. The drug is more costly than aspirin,
      and patients must have complete blood counts during the first 3 months of
      therapy. It is recommended for those who cannot take aspirin and may be more
      effective in certain groups--nonwhites, diabetics, and women and those with
      vertebrobasilar ischemia, intermittent claudication, unstable angina, and
      nonproliferative retinopathy.

PMID- 8149357
TI  - Pharmacodynamic interactions between phenytoin and valproate: individual and
      combined antiepileptic and neurotoxic actions in mice.
AB  - Although the current trend is to use monotherapy in the treatment of epilepsy,
      combination therapy is still employed in patients who have failed to respond to
      monotherapy. There is little clinical or experimental documentation of evidence
      against or in favor of anticonvulsant combination therapy. In this context,
      anticonvulsant and neurotoxic pharmacodynamic interactions between phenytoin
      (PHT) and valproate (VPA) were assessed in an experimental model in mice. All
      results were expressed in terms of brain drug concentrations for eliminating any
      pharmacokinetic interaction from the analysis. Both the median neurotoxic and the
      median anticonvulsant brain concentrations were determined for each drug used
      alone and for the combination. The interaction for the combination of PHT and VPA
      was shown to be supraadditive for the anticonvulsant activity, indicating an
      antiepileptic potentiation, whereas neurotoxicity was simply additive. These
      results suggest a potential benefit in terms of overall efficacy versus toxicity
      for the combination of PHT and VPA, as compared with PHT or VPA used alone.

PMID- 8149358
TI  - Comparison between a fast and a slow release preparation of levodopa and a
      combination of the two: a clinical and pharmacokinetic study.
AB  - After overnight drug withdrawal and in the fasting state, 11 patients with
      Parkinson's disease (PD) and a fluctuating response to chronic levodopa treatment
      were given, in random sequence on consecutive days, equivalent levodopa doses
      (with peripheral decarboxylase inhibitor) (a) as levodopa methyl ester (ME), (b)
      as Sinemet CR, or (c) as half the dose of ME together with a halved tablet of
      Sinemet CR. All patients turned ON rapidly after treatments a and c, but only
      half did so after treatment b. On period duration was longest after treatment c,
      intermediate after treatment a, and shortest after treatment b. Pharmacokinetic
      analysis in a subset of 6 patients revealed no significant difference between
      treatments a and c, although there was a trend for t1/2 to be longer after
      treatment c. We conclude that giving ME with a halved tablet of Sinemet CR
      provided a useful clinical balance between rapid onset and extended duration of
      action of at least the first levodopa intake of the day. In view of differing
      release profiles between whole and halved tablets of Sinemet CR, similar single
      dose pharmacokinetic studies, followed by sequential-dose clinical studies, are
      indicated when Sinemet CR 125 tablets soon become available.

PMID- 8149359
TI  - Pharmacokinetics of apomorphine in Parkinson's disease: plasma and cerebrospinal
      fluid levels in relation to motor responses.
AB  - In this study, we measured the relationship between plasma and cerebrospinal
      fluid (CSF) apomorphine levels and their clinical effects in two patients with
      Parkinson's disease (PD). After subcutaneous injection of apomorphine, serial
      samples of plasma and lumbal CSF were taken and serial scoring of motor responses
      was done using the Webster Rating Scale. The ratio of the highest level of
      apomorphine in CSF and plasma was 0.036 for patient A and 0.025 for patient B.
      The time lag between the highest level of apomorphine in plasma and CSF was 20
      min for patient A and 10 min for patient B. Plasma levels of apomorphine
      correlated weakly with clinical motor responses. However, we could establish a
      highly strong correlation between apomorphine CSF levels and clinical motor
      responses: 0.93 and 0.89 for patients A and B, respectively. We conclude that a
      two-compartment pharmacokinetic model explains the clinical effects of
      apomorphine better than does a one-compartment model. In a two-compartment model,
      clinical effect can clearly be correlated to apomorphine levels in the central
      compartment.

PMID- 8149360
TI  - L-tyrosine pharmacotherapy of schizophrenia: preliminary data.
AB  - The utility of L-tyrosine (10 g/day in four divided doses) as an adjuvant to
      molindone (150 mg/day) in the treatment of schizophrenia was investigated using a
      placebo-controlled, double-blind crossover design (3 weeks on L-tyrosine, 3 weeks
      on placebo). The objective of this inpatient study was to increase dopaminergic
      neural transmission along mesocortical projections in patients by increasing the
      precursor availability of L-tyrosine for dopamine biosynthesis. Theoretically,
      this approach might lessen both negative and positive symptoms of schizophrenia
      and improve frontal lobe-mediated neuropsychological performance. There was no
      evidence of statistically significant improvement conferred by L-tyrosine as
      measured by weekly Brief Psychiatric Rating Scale (BPRS), Schedule for the
      Assessment of Negative Symptoms (SANS), or Clinical Global Impressions (CGI)
      scales. The 12-h trough plasma level of L-tyrosine was significantly higher in
      all patients during the L-tyrosine phase of the study (t = -3.9, df = 20, p =
      0.0009). At the end of each 3-week study period, no significant differences could
      be found in Wisconsin Card Sorting Test (WCST) or memory test performance. Smooth
      pursuit eye movement (SPEM) performance had significantly more saccadic
      intrusions during the L-tyrosine supplementation phase compared to the placebo
      period. This increase in saccades during SPEM suggests that the tyrosine
      supplementation might have had some central effect.

PMID- 8149361
TI  - Buspirone in levodopa-induced dyskinesias.
AB  - We made a double-blind, crossover comparison of buspirone (10 mg orally, twice a
      day) and placebo in 10 patients with Parkinson's disease and levodopa-induced
      dyskinesias. The duration of the study was 3 weeks, for both buspirone and for
      placebo treatment. Chronic therapies remained unchanged. The extrapyramidal
      symptoms, dyskinesias, and anxious/depressive symptoms were evaluated at the
      beginning of the study and after the buspirone and placebo treatments. Seven
      patients concluded the trial. The extrapyramidal symptoms, evaluated in both the
      "off" and "on" states during an oral L-Dopa test, did not show any worsening
      during the trial. Buspirone significantly lessened the severity of levodopa
      induced dyskinesias in five of the seven patients, whereas it proved ineffective
      in the two patients with the mildest dyskinesias. There were no changes in the
      mild anxious and depressive symptoms at any time during the study. The activities
      of buspirone on the serotonin and dopamine systems might have led to the
      antidyskinetic effect we observed. At daily dosages of 20 mg, buspirone might
      prove effective in reducing levodopa-induced dyskinesias without worsening of
      parkinsonism.

PMID- 8149362
TI  - Platelet monoamine oxidase activity in neuroleptic-naive schizophrenic patients:
      lack of influence of chronic perphenazine treatment.
AB  - We investigated the possible relationship between schizophrenia, neuroleptic
      treatment, and platelet monoamine oxidase (MAO) activity. Platelet MAO activity
      was similar in neuroleptic-naive schizophrenic patients and healthy controls and
      was not affected by chronic (10-week) perphenazine treatment. A relationship
      between platelet MAO activity and central disturbances in schizophrenia remains
      uncertain.

PMID- 8149363
TI  - Lacrimation in Parkinson's disease.
AB  - The present study compares lacrimal secretion in control subjects and patients
      with Parkinson's disease with use of Schirmer's test. Tear secretion was
      decreased in Parkinson's disease. The reduction was more marked in stages III-IV
      than in stages I-II. The results are discussed in relationship with autonomic
      dysfunction in Parkinson's disease.

PMID- 8149364
TI  - Apomorphine increases blood glucose concentrations in Parkinson's disease.
AB  - Data from studies indicate that blood glucose levels may be influenced by
      stimulation of central D1 and D2 dopamine receptors. This is modulated by central
      dopamine receptor status. We studied apomorphine-induced increase in blood
      glucose levels in Parkinson's disease compared with those in Parkinsonian
      syndromes unresponsive to dopaminergic drugs. Results indicate that apomorphine
      induced blood glucose level increases are significant only in Parkinson's
      disease. As in the animal, this could possibly be explained by central dopamine
      receptor status.

PMID- 8149365
TI  - L-dopa malabsorption in a parkinsonian patient with Strongyloides stercoralis
      duodenitis.
AB  - We report a parkinsonian patient initially responding to L-dopa who developed a
      severe loss of drug efficacy due to Strongyloides stercoralis duodenitis. The
      patient was put on mebendazole and metronidazole, and the parasitosis abated,
      allowing L-dopa reduction by 33%. Our patient illustrates the advisability of
      searching for Strongyloides stercoralis when L-dopa malabsorption is suspected in
      Parkinson's disease.

PMID- 8149366
TI  - Apomorphine and diphasic dyskinesia.
AB  - We report on three observations of parkinsonian patients with levo-dopa-induced
      diphasic dyskinesias, who received subcutaneous apomorphine to reduce the
      duration of abnormal movements. Apomorphine was effective in reducing the
      duration of diphasic dyskinesias at doses higher than the threshold doses
      necessary to induce an "on" phase (mean increase: 43%). However, after a few
      months of treatment, apomorphine was ineffective in stopping abnormal movements,
      even when doses were increased. In two patients, apomorphine remained effective
      in the morning, but increased the intensity of the dyskinesias in the afternoon.
      Acute diurnal variations of the pharmacodynamic striatal response are suggested
      explanation for these clinical observations.

PMID- 8149367
TI  - Synthesis of dispirodioxanyl pseudo-oligosaccharides by selective protonic
      activation of isomeric glycosylfructoses in anhydrous hydrogen fluoride.
AB  - Dispirodioxanyl pseudotetrasaccharides 6-O-alpha-D-glucopyranosyl-alpha-D
      fructofuranose 6-O-alpha-D-glucopyranosyl-beta-D-fructofuranose 1,2':2,1'
      dianhydride, 5-O-alpha-D-glucopyranosyl-alpha-D-fructopyranose 5-O-alpha-D
      glucopyranosyl-beta-D-fructopyranose 1,2':2,1'-dianhydride, 4-O-alpha-D
      glucopyranosyl-alpha-D-fructofuranose 4-O-alpha-D-glucopyranosyl-beta-D
      fructopyranose 1,2':2,1'-dianhydride, 4-O-beta-D-galactopyranosyl-alpha-D
      fructofuranose 4-O-beta-D-galactopyranosyl-beta-D-fructopyranose 1,2':2,1'
      dianhydride, and 3-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 3-O-alpha-D
      glucopyranosyl-beta-D-fructofuranose 1,2':2,1'-dianhydride were respectively
      obtained, on a preparative scale, by dissolution of the isomeric
      glycosylfructoses palatinose, leucrose, maltulose, lactulose, and turanose in
      anhydrous hydrogen fluoride. The reaction, involving selective protonation at the
      free anomeric position of the fructose unit, was extended to the preparation of
      the pseudotrisaccharides 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose beta-D
      fructopyranose 1,2':2',1-dianhydride from palatinose and fructose, and to its 3-O
      , 4-O-, and 4'-O-glucosyl analogues using turanose and maltulose as the
      disaccharide precursor. The cross-reactions of palatinose with maltulose and with
      leucrose resulted in the preparation of 6-O-alpha-D-glucopyranosyl-alpha-D
      fructofuranose 4-O-alpha-D-glucopyranosyl-beta-D-fructopyranose 1,2':2,1'
      dianhydride and 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 5-O-alpha-D
      glucopyranosyl-beta-D-fructopyranose 1,2':2,1'-dianhydride, respectively.

PMID- 8149368
TI  - An improved procedure for the analysis of linkage positions in 2-acetamido-2
      deoxy-D-glucopyranosyl residues by the reductive-cleavage method.
AB  - The conditions of the reductive-cleavage method were modified to allow
      simultaneous analysis of 2-acetamido-2-deoxy-D-glucopyranosyl residues and
      monosaccharides of other classes. Methyl 2-deoxy-3,4,6-tri-O-methyl-2-(N
      methylacetamido)-beta-D-glucopyran oside was found to undergo transglycosidation
      under reductive-cleavage conditions when the reaction was quenched with an
      alcohol. Transglycosidation proceeded via an oxazolinium-ion intermediate, which
      then acted as a glycosyl donor to form an anomerically pure product. Time-course
      studies showed that in the presence of trimethylsilyl trifluoromethanesulfonate
      (Me3SiOSO2CF3), 4 h were required for complete conversion of the substrate into
      this intermediate, which was then trapped with methanol-d4. When the reaction was
      conducted in the presence of a mixture of trimethylsilyl methanesulfonate
      (Me3SiOSO2Me) and boron trifluoride etherate (BF3.OEt2) or with BF3.OEt2 alone,
      24 h and 48 h, respectively, were required for complete conversion. The alpha
      anomer was unreactive after 24 h under all conditions, confirming earlier
      results. Reaction with racemic 2-butanol yielded a pair of diastereomers, in a
      1:1 ratio, which were distinguishable by their GLC retention times and their 1H
      NMR spectra. Reaction with (S)-2-butanol gave only one of the diastereomeric
      products. These experiments demonstrated the feasibility of using the reductive
      cleavage method to determine the absolute configuration of 2-acetamido sugars.

PMID- 8149369
TI  - Structural studies of endopolygalacturonase-resistant fragments of an antiulcer
      pectin from the roots of Bupleurum falcatum L.
AB  - The endo-alpha-(1-->4)-polygalacturonase-resistant fractions (PG-1, PG-2, and PG
      3) from an antiulcer pectin (Bupleuran 2IIc), isolated from the roots of
      Bupleurum falcatum L., were further analysed by lithium degradation. The results
      indicated that PG-1 contained a small proportion of long, branched arabinosyl
      chains and a large proportion of short, neutral oligosaccharide chains. GLC-MS
      analysis showed that, after methylation the short, neutral oligosaccharide
      fraction consisted of at least 22 kinds of di- to tetra-saccharide alditols, such
      as Gal-(1-->4)-Rha-ol (a major component), Ara-(1-->4)-Rha-ol, Glc-(1-->4)-Rha
      ol, Ara-->Ara-->Ara-ol, and Ara-->Ara-->Ara-->Ara-ol (minor components) in
      addition to heteroglycosyl alditols. After deesterification, PG-2 and PG-3 were
      digested with endo-alpha-(1-->4)-polygalacturonase again, and the enzyme
      resistant intermediate size fraction (PG-2') was purified. Component sugar
      analysis indicated that PG-2' contained 2-Me-Fuc, 2-Me-Xyl, apiose (Api), aceric
      acid (AceA), 3-deoxy-D-lyxo-heptulosaric acid (Dha), and 3-deoxy-D-manno-2
      octulosonic acid (Kdo) in addition to Rha, Fuc, Ara, Xyl, Man, Gal, Glc, GalA,
      and GlcA. Lithium degradation of PG-2' gave mainly a pentosyl-->6-deoxyhexosyl-
      >6-deoxyhexosyl-->pentitol fragment, with some neutral di- and tri-saccharide
      alditols, including a pentosyl-->deoxyhexitol. Methylation analysis of these
      degradation products indicated that they contained terminal Rha, Araf, Fuc, Xyl,
      and Gal, 4-linked Rha, 3-linked Fuc, 3-linked Ara, and 3'-linked Api. Bupleuran
      2IIc was eluted as essentially a single peak on gel filtration on Sepharose CL
      6B. The neutral sugar content of the successive fractions increased with
      increasing molecular weight, but each fraction also contained, in addition to
      Rha, Ara, and Gal, 2-Me-Fuc, 2-Me-Xyl, and Api.

PMID- 8149371
TI  - Protonic reactivity of sucrose in anhydrous hydrogen fluoride.
AB  - Sucrose reacts quantitatively, when dissolved at high concentration in anhydrous
      hydrogen fluoride, to afford a complex mixture of difructose dianhydrides and
      their glucosylated derivatives. Oligo- and small poly-saccharides up to dp 14
      were detected by FABMS. Oligosaccharides up to dp 4, representing approximately
      50% of the total mixture, have been isolated and characterized by mass
      spectrometry, 13C NMR spectroscopy, and comparison with reference
      oligosaccharides previously obtained by unambiguous synthesis. alpha-D
      Fructofuranose beta-D-fructopyranose 1,2':2,1'-dianhydride is the main
      spirodioxanyl pseudodisaccharide entity found in the mixture, either free or
      glucosylated at C-6 and to a lesser extent at C-3, C-4, C-4', C-6, and C-5' C-6.
      Minor spirodioxanyl pseudodisaccharide components are di-beta-D-fructopyranose
      1,2':2,1'-dianhydride, which has also been found glucosylated at C-5, alpha-D
      fructopyranose beta-D-fructopyranose 1,2':2,1'-dianhydride, beta-D-fructofuranose
      beta-D-fructopyranose 1,2':2,3'-dianhydride, and the 6,6'-diglucosylated alpha-D
      fructofuranose beta-D-fructofuranose 1,2':2,1'-dianhydride. A 13C NMR examination
      of the higher mass oligomeric fraction suggests that it may involve 6-O
      isomaltooligoglycosyl alpha-D-fructofuranose beta-D-fructopyranose 1,2':2,1'
      dianhydrides as the main structural components. The reaction of sucrose in
      anhydrous HF is believed to proceed through initial selective protonic activation
      of the tertiary anomeric carbon atom of the fructose moiety, resulting in the
      quantitative formation of difructose dianhydrides, which subsequently suffer
      electrophilic substitution by glucopyranosyl oxocarbenium ions generated in a
      second step by action of the HF.

PMID- 8149370
TI  - Specificity studies of the GDP-[L]-fucose: 2-acetamido-2-deoxy-beta-[D]-glucoside
      (Fuc-->Asn-linked GlcNAc) 6-alpha-[L]-fucosyltransferase from rat-liver Golgi
      membranes.
AB  - The specificity of Golgi-membrane glycoprotein 6-alpha-[L]-fucosyltransferase
      [GDP-[L]-fucose: 2-acetamido-2-deoxy- beta-[D]-glucoside (Fuc-->Asn-linked
      GlcNAc) 6-alpha-[L]-fucosyltransferase; EC 2.4.1.68] has been assessed with
      regard to substrate covalent structures and the effect of a protein matrix on the
      conformational display of those covalent structures. Specificity was studied by
      direct comparison of the substrate quality of nine 6-biotinamidohexanoylAsn (= R)
      derivatives of intermediates and products in the pathway from Man5GlcNAc2-R to a
      fully sialylated biantennary complex-type glycan. The Man5 derivative and the
      sialic acid-containing glycans were completely inactive as substrates. The other
      glycans were all fucosylated; the best substrate was GlcNAcMan3GlcNAc2-R. The
      protein-matrix effect was studied by comparing the substrate quality of the same
      6-biotinamidohexanoylAsn derivatives as well as the corresponding biotinylAsn
      derivatives free in solution and bound to streptavidin. On the basis of a model
      derived from the known 3D structure of biotin (biocytin)-saturated streptavidin,
      it was predicted that the fucosylation site in the substrates would be completely
      masked in the biotin-binding pocket in the biotinyl derivatives (proximal
      display), and at least partially masked in the 6-biotinamidohexanoyl derivatives
      (distal display). The activity measurements were in agreement with these
      predictions; the glycan structures GlcNAcMan5GlcNAc2-, GlcNAcMan3GlcNAc2-, and
      GlcNAc2-Man3GlcNAc2- were readily fucosylated as derivatives free in solution,
      but were totally inert in the proximal complex with streptavidin. In the distal
      complexes the latter two structures were found to be fucosylated very slowly
      while the former structure was inactive.

PMID- 8149372
TI  - Glycamine formation via reductive amination of oligosaccharides with benzylamine:
      efficient coupling of oligosaccharides to protein.
AB  - The conventional reagents for the reductive amination of sugars, ammonium salts
      or ammonia, require relatively harsh conditions such as high temperatures or high
      concentrations. In addition, they give substantial amounts of dimeric byproducts.
      We have developed a method of using benzylamine as a donor to achieve near
      quantitative amination of reducing oligosaccharides. Benzylamine reacts with
      reducing oligosaccharides faster and yields less dimeric byproduct than ammonium
      ion, rendering it especially advantageous for preparative operation. In
      combination with a heterobifunctional reagent, 5-[N-(2,2
      dimethoxyethyl)carbamoyl]pentanoyl azide, [Lee et al. Biochemistry, 28 (1989)
      1856-1861], we could couple a nearly maximal number of phosphorylated
      mannopentaose molecules to ribonuclease A via its primary amino groups.

PMID- 8149373
TI  - The crystal and molecular structure of the trisaccharide erlose trihydrate.
AB  - Erlose [beta-D-fructofuranosyl O-alpha-D-glucopyranosyl-(1-->4)-D
      glucopyranoside] trihydrate, C18H32 O16.3H2O, M(r) = 558.48, is orthorhombic,
      P2(1)2(1)2(1) with a = 31.164(7), b = 13.111(5), c = 11.636(5) A, and Z = 8. The
      structure was solved by direct methods, and refined to R = 0.035 for 3926
      observed reflections. The unit cell contains two independent molecules having a
      similar conformation. The conformation of the alpha-(1-->2) glycosidic linkage is
      similar to that observed in erlose monohydrate, whereas the conformation of the
      alpha-(1-->4) glycosidic linkage differs significantly. The molecule has no
      intramolecular hydrogen-bonds except for the minor components of three-center
      bonds, but indirect intramolecular hydrogen-bonds through the water molecules are
      formed. The hydrogen-bond system in the crystal structure consists of infinite
      and finite chains crosslinked by water molecules.

PMID- 8149374
TI  - New acyclic analogues of lipid A: synthesis of 4-phosphonoxybutyl and 3
      phosphonoxypropyl glycosides of 2-amino-2-deoxy-D-glucose.
AB  - Several analogues of lipid A have been synthesized, in which the reducing
      monosaccharide moiety of the parent molecule has been replaced by an acyclic
      spacer. The new compounds show high endotoxic activity and are able to protect
      neutropenic mice against pseudomonas infection, two properties characteristic of
      LPS-like molecules.

PMID- 8149376
TI  - Chemical and enzymatic synthesis of multivalent sialoglycopeptides.
AB  - Linear and branched glycopeptides containing multiple sialyl-N-acetyllactosamine
      side chains have been synthesized using a combined chemical and enzymatic
      approach. Peptide backbones in which beta-GlcNAc-Asn residues were incorporated
      were obtained in good yields by optimized solid-phase synthesis following the Boc
      strategy. The resulting multivalent glycopeptides were galactosylated in near
      quantitative yields using bovine galactosyltransferase, UDP-galactose, and calf
      alkaline phosphatase that destroys the inhibiting side product UDP. Subsequent
      enzymatic sialylation yielded the desired glycopeptides containing asparagine
      linked sialyl-N-acetyllactosamine side chains. The compounds were characterized
      by 1H NMR and FABMS. Recombinant sialyltransferase and CMP-sialate synthetase
      were used for the enzymatic synthesis of sialosides on a preparative scale. The
      synthetic glycopeptides were tested as inhibitors of influenza virus to cells,
      revealing that most of the multivalent sialoglycopeptides exhibit increased
      binding that depends on the spacing when compared to monovalent compounds. A
      possible mechanism for increased binding is proposed.

PMID- 8149375
TI  - Synthesis of O-[2-acetamido-2-deoxy-6-O-stearoyl- and -6-O-(2
      tetradecylhexadecanoyl)-beta-D-glucopyranosyl]-(1-->4)-N- acetylnormuramoyl-L
      alpha-aminobutanoyl-D-isoglutamine, lipophilic disaccharide analogues of MDP.
AB  - Silver triflate-promoted condensation of 3,4,6-tri-O-acetyl-2-deoxy-2-
      phthalimido-beta-D-glucopyranosyl bromide (1) with benzyl 2-acetamido-6-O-benzyl
      2-deoxy-3-O- (methoxycarbonyl)methyl-alpha-D-glucopyranoside (4) afforded the key
      compound, benzyl 2-acetamido-6-O-benzyl-2-deoxy-3-O- (methoxy-carbonyl)methyl-4-O
      (3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-b eta-D- glucopyranosyl)-alpha-D
      glucopyranoside (5), which after deprotection was transformed into acid 10.
      Condensation of 10 with the benzyl ester of L-alpha-aminobutanoyl-D-isoglutamine
      and deisopropylidenation of the product 11 afforded the benzyl ester of N-(2-O
      [benzyl 2-acetamido-4-O-(2-acetamido-3-O-benzyloxymethyl-2- deoxy-beta-D
      glucopyranosyl)-6-O-benzyl-2,3-dideoxy-alpha-D-glucopyra nosid-3- yl]glycoloyl)-L
      alpha-aminobutanoyl-D-isoglutamine (12). Partial O-acylation of 12 and
      hydrogenolysis of protecting groups gave the 6-O-stearoyl- and 6-O-(2
      tetradecylhexadecanoyl)-disaccharide-dipeptides 17 and 18, respectively.
      Pyrogenicity and adjuvant activity in cell-mediated immunity are reported.

PMID- 8149377
TI  - Structure and physical properties of the extracellular polysaccharide PS-P4
      produced by Sphingomonas paucimobilis P4 (DSM 6418).
AB  - A new strain, Sphingomonas paucimobilis P4 (DSM 6418), was found during a
      screening programme for exopolysaccharide-producing bacteria. The highly viscous
      fermentation broth yields a polysaccharide (up to 10 kg/m3), named PS-P4, and
      shows thixotropic flow behaviour. In the presence of phosphate ions, PS-P4 forms
      aqueous gels after heating and cooling at alkaline pH. After isolation and
      purification of the exopolysaccharide, structural analysis by 1D and 2D 1H NMR
      spectroscopy and mass spectrometry was performed. The deacylated
      exopolysaccharide has the following repeating trisaccharide structure:-->4)-beta
      D-Glcp-(1-->4)-alpha-L-Rhap-(1-->3)-beta-D- Glcp(1-->Additionally, the presence
      of ester-bound acetic acid, D-glyceric acid, and (R)-3-hydroxybutyric acid in the
      native polysaccharide was demonstrated.

PMID- 8149378
TI  - Structural studies of fungal cell-wall polysaccharides from two strains of
      Talaromyces flavus.
AB  - The water-soluble cell-wall polysaccharides isolated from strains CBS 352.72 and
      310.38 of Talaromyces flavus have been investigated by chemical analyses and NMR
      studies. Two different skeletons coexist, having the structures: [formula:see
      text]. The small differences between the polysaccharides isolated from both
      strains are probably due to slight diminution of branching in strain 352.72, as
      compared with strain 310.38.

PMID- 8149379
TI  - Recognition of synthetic O-methyl, epimeric, and amino analogues of the acceptor
      alpha-L-Fuc p-(1-->2)-beta-D-Gal p-OR by the blood-group A and B gene-specified
      glycosyltransferases.
AB  - The disaccharide alpha-L-Fuc p-(1-->2)-beta-D-Gal p-O-(CH2)7CH3 (6) is an
      acceptor for the glycosyltransferases responsible for the biosynthesis of the A
      and B blood-group antigens. These enzymes respectively transfer GalNAc and Gal in
      an alpha linkage to OH-3 of the Gal residue in 6. All eight possible O-methyl,
      epimeric, and amino analogues of 6 having modifications on the target Gal residue
      were chemically synthesized and kinetically evaluated both as substrates and
      inhibitors for the A and B glycosyltransferases. The results support earlier
      findings that both enzymes will tolerate replacement of the hydroxyl groups at
      the 3 and 6 positions of the Gal residue. Substitution at or replacement of OH-4
      of the Gal residue, however abolishes recognition. The 6-O-methyl and 6-amino
      compounds are substrates for both enzymes while the 3-epimeric (10) and 3-amino
      (12) compounds are inhibitors. For the B transferase, 10 is a competitive
      inhibitor with a Ki of 7.8 microM. Attempts to determine a Ki for 12 with the B
      transferase were unsuccessful because of a complex mode of inhibition. Similarly,
      both 10 and 12 are potent inhibitors of the A transferase, but the inhibition
      constants could not be calculated because of a complex mode of inhibition,
      resembling that for the B transferase. With the A transferase, 12 had an
      estimated Ki in the 200 nM range.

PMID- 8149380
TI  - Synthesis of allyl 3-deoxy- and 4-deoxy-beta-D-galactopyranoside and simultaneous
      preparations of Gal(1-->2)- and Gal(1-->3)-linked disaccharide glycosides.
AB  - Syntheses of galactose derivatives that are useful in probing the binding
      specificity of galactose-specific lectins are reported. These include allyl 3
      deoxy- and 4-deoxy-beta-D-xylo-hexopyranoside and several disaccharide glycosides
      having Gal(1-->2) and Gal(1-->3) linkages. The beta-linked Gal disaccharide
      isomers were produced using 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl
      bromide as glycosyl donor and the 4,6-O-benzylidene derivatives of allyl beta-D
      galactopyranoside, alpha-D-glucopyranoside, alpha-D-mannopyranoside, and 2
      acetamido-2-deoxy-alpha-D-galactopyranoside as acceptors. Only the Gal(1-->3)
      linked disaccharide was obtained when the benzylidene derivatives of the
      mannopyranoside and 2-acetamido-2-deoxygalactopyranoside were used. Attempts at
      the preparation of Gal(alpha, 1-->2)Gal and Gal(alpha, 1-->3)Gal disaccharide
      glycosides were made using the same strategy, but employing the 1-trichloro
      acetimidate or 1-N-methylacetimidate of 2,3,4,6-tetra-O-benzyl-D-galactopyranose
      as the glycosyl donor. The latter imidate produced a mixture of Gal(alpha, 1-
      >2)Gal and Gal(alpha, 1-->3)Gal derivatives as major products, but the former
      gave the Gal(beta, 1-->2)Gal isomer as the major product.

PMID- 8149381
TI  - Structural features and hypoglycemic activities of two polysaccharides from a hot
      water extract of Agrocybe cylindracea.
AB  - A glucan (AG-HN1, [alpha]D +24 degrees) and a heteroglycan (AG-HN2, [alpha]D +26
      degrees) were isolated from a hot-water extract of the fruiting bodies of
      Agrocybe cylindracea. The structures were investigated by a combination of
      chemical and spectroscopic methods. The results indicated that high molecular
      weight glucan AG-HN1 is primarily a beta-(1-->6)-branched (1-->3)-beta-D-glucan
      containing small amounts of (1-->4)-linked and (1-->6)-linked glucopyranosyl
      residues. Low molecular weight heteroglycan AG-HN2 gives galactose, glucose,
      fucose, and mannose on hydrolysis and appears to be chiefly composed of (1-->6)
      linked gluco- and galacto-pyranosyl residues, many of them branched, and various
      nonreducing terminal residues. AG-HN1 showed a remarkable hypoglycemic activity
      in both normal and streptozotocin-induced diabetic mice by ip administration, and
      its activity was higher than that of AG-HN2.

PMID- 8149382
TI  - A 1,2-alpha-D-mannosidase from a Bacillus sp.: purification, characterization,
      and mode of action.
AB  - A 1,2-alpha-D-mannosidase was purified to homogeneity from the culture
      supernatant of Bacillus sp. M-90, which was isolated from soil by enrichment
      culture on baker's yeast mannan. The purified enzyme had M(r) 380,000 Da, and was
      comprised of two apparently identical 190,000 Da subunits. It had a neutral
      optimum pH (7.0) and an isoelectric point of 3.6. The enzyme was highly specific
      for alpha 1,2-linked D-mannose oligosaccharides. An N-linked high-mannose type
      oligosaccharide, Man9GlcNAc2, was a good substrate, yielding Man5GlcNAc2, and the
      alpha 1,2-linked side chains of Saccharomyces cerevisiae mannan were also
      specifically hydrolyzed by the enzyme. p-Nitrophenyl alpha-D-mannopyranoside and
      1,2-alpha-D-mannobiitol were not hydrolyzed at all. Calcium ion, 1-deoxyman
      nojirimycin, and swainsonine had no effect on the enzyme, but the activity was
      completely inhibited by EDTA. The mode of action on alpha 1,2-linked
      mannotetraose indicated that the enzyme is an exo-1,2-alpha-D-mannanase.

PMID- 8149383
TI  - New pyruvylated, glycosylated acyltrehaloses from Mycobacterium smegmatis
      strains, and their implications for phage resistance in mycobacteria.
AB  - Phage resistance and apparent lysogenization of Mycobacterium smegmatis due to
      infection with mycobacteriophage D29 results in the emergence of new variations
      of the pyruvylated, acylated trehaloses described by Saadat and Ballou, J. Biol.
      Chem. 258 (1983) 1813-1818. Thin-layer chromatography of the glycolipids from two
      strains of phage-resistant M. smegmatis (mc(2)22 and mc(2)11) and comparison with
      those from phage-sensitive strains revealed a new, more mobile glycolipid in each
      case. The structures of these acyltrehalose-containing lipooligosaccharides were
      elucidated by a combination of gas-liquid chromatography-mass spectrometry,
      methylation analysis, 1H and 13C NMR spectroscopy, and fast-atom bombardment mass
      spectrometry. The glycolipid from M. smegmatis mc(2)22 is beta-D-Glcp-(1-->3)-4,6
      O-(1-methoxycarbonylethylidene)-beta-D-Glc p-(1-->4)- beta-D-Glcp-(1-->6)-2-O
      acyl-alpha-D-Glcp-(<==>1)-3,4-O-acyl-alpha-D-Glc p and that from M. smegmatis
      mc(2)11 is 4,6-O-(1-methoxycarbonylethylidene)-3-O-Me-beta-D-Glcp-(1-->3)-4,6 -O-
      (1-methoxycarbonylethylidene)-beta-D-Glcp-(1-->4)-beta-D-Glcp-(1-- >6)-2-O-acyl-
      alpha-D-Glcp-(1<==>1)-3,4-di-O-acyl-alpha-D-Glcp. These differ from the original
      pyruvylated glycolipids of Saadat and Ballou in the extent of their O-acylation
      and O-methylation. The findings are the first example of the definition of a
      chemical basis for phage resistance and presumed lysogeny in mycobacteria, and
      show parallels to related changes in gram-negative enteric bacteria.

PMID- 8149384
TI  - A canine model of acute coronary artery thrombosis for the evaluation of
      reperfusion strategies.
AB  - A model of coronary artery thrombosis which: (1) provides a stable thrombus; (2)
      incorporates intimal injury; (3) has a low mortality rate; (4) responds
      predictably to thrombolytic therapy, and (5) is technically simple, was
      developed. Intimal injury was produced proximal to a critical stenosis and
      followed by the infusion of a blood and thrombin mixture into the injured
      segment. After thrombus formation flow remained absent in all control animals (n
      = 7). Microscopy showed intimal injury and coronary thrombosis with platelets
      adherent to the subendothelium. In animals treated with tissue plasminogen
      activator (n = 7) flow returned to > 60% of baseline at 20.2 +/- 7.7 min and was
      cyclical. Mortality and complications were infrequent. This model is useful in
      investigations of reperfusion therapy.

PMID- 8149385
TI  - Left-ventricular hypertrophy in the spontaneously hypertensive rat: effect of ACE
      inhibitors on ultrastructural morphology.
AB  - The ACE inhibitors cilazapril and captopril were administered at 10 and 100
      mg/day, respectively, to spontaneously hypertensive (SHR) and normotensive Wistar
      Kyoto rats (WKY) from the 12th to the 22nd week of life. Both drugs produced
      statistically significant reductions in systolic and diastolic blood pressure,
      left-ventricular mass and index of left-ventricular hypertrophy in SHR. After
      cilazapril treatment, the morphology of SHR cardiocytes became similar to that in
      untreated normotensive rats, while in captopril-treated rats, myofibrils were
      disarranged, obliquely oriented and smaller than normal, with areas of electron
      transparent sarcoplasm separating the myofibril bundles; mitochondria were also
      altered. In WKY rats, we observed no statistically significant changes in blood
      pressure, ventricular weight and hypertrophy index between the two drugs;
      however, there were different effects of the two drugs on the ultrastructural
      morphology of the myocardium. These observations suggest that these two
      molecularly dissimilar ACE inhibitors act differently at the tissue level despite
      similar effects on blood pressure and left-ventricular mass.

PMID- 8149386
TI  - Noninvasive methods in the early detection of restenosis after percutaneous
      transluminal angioplasty in peripheral arteries.
AB  - In a prospective study, several noninvasive methods were evaluated in the early
      detection of restenosis after percutaneous transluminal angioplasty in peripheral
      arteries. Sensitivity and specificity of various noninvasive resting and exercise
      methods for the detection of restenosis were determined. It is concluded that
      noninvasive follow-up after percutaneous transluminal angioplasty in peripheral
      arteries requires exercise testing with determination of ankle-arm index or
      segmental arterial pulse oscillography for the early detection of restenosis.

PMID- 8149387
TI  - Relationship between exercise tolerance, hemodynamics at rest and during exercise
      and ejection fraction, and their prognostic relevance in asymptomatic
      postinfarction patients.
AB  - In 309 postmyocardial infarction patients (age 40 +/- 7.7 years) without
      persistent ischemia there is only a weak correlation between ejection fraction
      (EF) and exercise tolerance (r = 0.45, p < 0.01), and between EF and maximum
      cardiac output (CO; r = 0.41, p < 0.01) and maximum pulmonary capillary wedge
      pressure (PCWP; r = -0.32, p < 0.001). The same was true for exercise tolerance
      and maximum PCWP (r = -0.53, p < 0.001). A big scattering of individual values
      could be observed. Although we found a high positive correlation between maximum
      CO and exercise tolerance (r = 0.80, p < 0.001), in individual cases a low CO
      could be related to high exercise tolerance and vice versa. In the multivariate
      analysis, only the heart volume/kg body weight and maximum PCWP could be shown to
      be of independent prognostic importance for survival and/or mortality in the
      following years (chi 2 = 5.9, p < 0.015 and chi 2 = 7.2, p < 0.007,
      respectively).

PMID- 8149388
TI  - Ambulatory electrocardiographic findings in top athletes, athletic students and
      control subjects.
AB  - Aim of the present study was to evaluate 24 h electrocardiographic recording in
      30 top athletes, 30 athletic students and 30 sedentary control subjects. Each
      group consisted of 15 males and 15 females and were matched for age (about 24
      years). Training was not allowed during the recording. Top athletes had the
      lowest diurnal and nocturnal heart rate, but the difference between top athletes
      and athletic students was far less pronounced than between athletic students and
      controls. This may indicate that bradycardia reaches a lower limit with moderate
      degrees of training. Atrioventricular (AV) block II was found in 3 top athletes
      and 4 athletic students and in none of the subjects, the longest pause being 2.4
      s in both athletic groups. Most episodes occurred during night and nearly all
      were Mobitz type I. In all cases of AV block II the QRS complexes were narrow and
      AV block III did not occur. SA block was found in 3 top athletes, 1 athletic
      student and 1 control subject, the longest pause being 3.1, 2.9 and 1.9 s,
      respectively. Ventricular premature beats were rare in all groups and complex
      ventricular arrhythmias were not found. Half of the subjects were in Lown class
      0, the other half in Lown class 1. Supraventricular premature beats were also
      scarce and most frequent in top athletes, followed by athletic students and
      sedentary controls (2.0, 1.0, 0.7 beats/h, respectively).

PMID- 8149389
TI  - Electrocardiographic findings of repolarization in athletic students and control
      subjects.
AB  - We have investigated resting electrocardiograms in 1,299 athletic students and
      151 sedentary control subjects. ST elevations were more frequent and pronounced
      in athletes compared to controls, whereas there was no difference in ST
      depressions. Athletes with ST elevation above 2 mm were characterized by lower
      heart rate, increased PQ duration, increased indices of left, right and septal
      hypertrophy and T wave amplitude. Negative T waves in 3 of 6 precordial leads, V3
      6, were found in 1.5% of athletes and 0.7% of controls, and in V5-6 in 0.4% of
      athletes and none of controls, the differences not being significant. Athletes
      had significantly more often a T wave axis between +30 and -180 degrees and less
      often a frontal T wave axis between +30 and +180 degrees. The mean QRS-T angle
      was significantly greater in athletes, and U waves were more prominent. Analyzing
      athletes with QTc below and above 0.430 s, we found an increased heart rate, QRS
      duration, ST depression and a more pronounced left QRS axis in the group with QTc
      above 0.430 s. There was a positive correlation between QTc and heart rate which
      indicates that the use of Bazett's formula leads to an underestimation of QTc at
      lower heart rates and to an overestimation at higher heart rates. Bazett's
      formula does not provide an adequate correction for heart rate and should be used
      with caution. Our finding of a prolonged QTc in athletes compared to control
      subjects in spite of lower heart rate in the athletic group demonstrates that a
      real QTc prolongation exists in athletes.

PMID- 8149390
TI  - Rare association of congenital bicuspid aortic valve, annuloaortic ectasia, and
      anomalous origin of left circumflex coronary artery.
AB  - A bicuspid aortic valve (BAV) is one of the most common congenital heart
      anomalies. Although each annuloaortic ectasia (AAE) and malformation of the left
      coronary artery has been described as a complication of BAV, no case associated
      with both abnormalities has been reported previously. We present here a very rare
      case of congenital BAV complicated by AAE and the anomalous origin of the left
      coronary artery.

PMID- 8149391
TI  - Pioneering change: the first female dean of a dental school.

PMID- 8149392
TI  - Understanding and addressing a woman's esthetic needs.

PMID- 8149393
TI  - A look at women's health issues.
AB  - Women's health issues have become the focus of much debate. A critical question
      in that debate centers on gender bias in medical research, which may result in
      bias in treatment. In this article, several disease processes are examined as
      they relate to women today. The areas of uncertainty in treatment, as well as
      areas of needed research, are highlighted.

PMID- 8149394
TI  - Breast carcinoma metastatic to the mandible.

PMID- 8149395
TI  - Aging and oral health: implications for women.
AB  - Of the 30 million Americans over age 65, 18.3 million are women and it is
      estimated that between 1989 and 2030, women will make up an increasingly large
      segment of this group. As one ages, the risk of chronic disease increases. These
      diseases and their treatment can have a significant impact on oral health. This
      article will discuss relevant issues in providing oral health care for older
      women. The demographics of aging in women, chronic diseases commonly seen in
      older women, and the impact of these diseases on oral health treatment planning
      will also be discussed. The article will highlight the importance of prevention
      of oral diseases throughout a woman's lifetime.

PMID- 8149396
TI  - Alteration in female sex hormones: their effect on oral tissues and dental
      treatment.
AB  - This article will discuss and describe the various oral manifestations that occur
      during the life cycles of the female when there is an alteration in the sex
      hormones--puberty, menstruation, pregnancy, and menopause. The effect of oral
      contraceptives on the oral tissues and dental treatment will also be discussed.

PMID- 8149397
TI  - Addressing snoring and obstructive sleep apnea: a problem often overlooked in
      women.

PMID- 8149398
TI  - Oral manifestations of menopause.
AB  - Menopause is a normal developmental stage in a woman's life, marking the
      permanent cessation of menstruation. It is the result of irreversible changes in
      the hormonal and reproductive functions of the ovaries. Menopause is accompanied
      by a number of characteristic physical changes; some of which occur in the oral
      cavity. The two most common oral manifestations of menopause are: oral
      discomfort, including pain, a burning sensation, dryness, and altered taste
      perception; and alveolar bone loss as a result of osteoporosis. Although
      menopause has been recognized for centuries, it has only been recently that the
      study of menopause has gained much attention. The purpose of this article is to
      review the basic physiology of menopause, and to present the etiology of the oral
      manifestations associated with menopause.

PMID- 8149399
TI  - An overview of anorexia and bulimia nervosa, and the impact of eating disorders
      on the oral cavity.
AB  - The two most common eating disorders, anorexia nervosa and bulimia nervosa, can
      severely impact oral health. This article will discuss and describe the nature of
      these disorders and attempt to explain why mostly women suffer from them. In
      addition, the signs and symptoms of these disorders will be described as they
      present on medical and oral examination, and recommendations for rehabilitating
      these patients will be presented.

PMID- 8149400
TI  - Psychodynamic factors contributing to esthetic dental failures.
AB  - Traditionally, dentistry has focused on biomedical and mechanotechnical
      approaches to patients' dental health care. Objective and quantifiable
      measurements, such as tooth form, occlusal function, color, and biological
      compatibility, are conventional indicators of success or failure. However, unlike
      most facets of dental practice, the attainment of an enhanced facial and dental
      appearance is influenced and measured by more abstract, psychological factors
      such as perception, ideal body image, self-image, and personal motivation. These
      complex concepts are affected by emotional and personality factors that develop
      during the life cycle. This article will explore a psychodynamic perspective of
      patients who are dissatisfied with the esthetics of their dental treatment,
      although the result may be functionally and esthetically acceptable.

PMID- 8149401
TI  - Women in dentistry: building a powerful and successful practice.

PMID- 8149402
TI  - Effect of serotonin and tricyclic antidepressants on intracellular calcium
      concentrations in Spisula oocytes.
AB  - Microspectrofluorometry and video imaging techniques were used to study and to
      compare the changes in intracellular calcium concentrations ([Ca2+]i) of
      individual Fura-2 loaded Spisula oocytes treated with serotonin (5
      hydroxytryptamine, 5-HT) or tricyclic antidepressants. In the present study, we
      showed that 5-HT increased [Ca2+]i in freshly isolated Spisula oocytes suspended
      in artificial sea water. In the absence of extracellular Ca2+, 5-HT did not
      influence [Ca2+]i. Stimulation of [Ca2+]i by 5-HT was blocked by calcium channel
      blocker, e.g. verapamil, and by tricyclic antidepressants. These observations
      combined with our previous results on the effects of 5-HT, tricyclic
      antidepressants and verapamil on calcium uptake suggest that the increase in
      [Ca2+]i induced by 5-HT results from an influx of extracellular calcium through
      calcium channels, which can be blocked by tricyclic antidepressants. The use of
      the Fura-2 imaging technique allowed single-cell measurements and defined changes
      induced by 5-HT in [Ca2+]i which is the net result of calcium uptake and release
      of intracellular calcium from storage sites in individual Spisula oocytes.

PMID- 8149403
TI  - The plasma membrane calcium pump is the preferred calpain substrate within the
      erythrocyte.
AB  - The activation of calpain in normal human erythrocytes incubated in the presence
      of Ca2+ and the Ca2+ ionophore A23187 led to the decline of the Ca(2+)-dependent
      ATPase activity of the cells. Preloading of the erythrocyte with an anticalpain
      antibody prevented the decline. The pump was also inactivated by applied to
      isolated erythrocyte plasma membranes. The decline of the pump activity
      corresponded to the degradation of the pump protein and was inversely correlated
      to the amount of the natural inhibitor of calpain, calpastatin, present in the
      cells. In erythrocytes containing only 50% of the normal level the degradation
      started at a concentration of Ca2+ significantly lower than in normal cells. A
      comparison of the concentrations of Ca2+ required for the degradation of a number
      of erythrocyte membrane proteins showed that the Ca2+ pump and band 3 were the
      most sensitive. All other membrane proteins tested were attacked at higher levels
      of intracellular Ca2+. Thus, the degradation of the Ca2+ pump protein may be a
      simple and sensitive means to monitor calpain activation in vivo. Furthermore,
      the results have shown that the calpastatin level correlated directly with the
      amount of activable calpain and with the concentration of Ca2+ required to
      trigger the activation process.

PMID- 8149404
TI  - Spontaneous calcium oscillations in Xenopus laevis melanotrope cells are mediated
      by omega-conotoxin sensitive calcium channels.
AB  - The dynamics of intracellular Ca2+ signalling in single melanotrope cells of the
      pituitary gland of the amphibian Xenopus laevis have been studied by means of a
      digital imaging technique using the fluorescent dye Fura-2. When placed in vitro,
      the majority of the cells (77%) displayed spontaneous oscillatory changes in the
      free cytosolic Ca2+ concentration with a frequency of 1 +/- 0.25 (SD) min-1. The
      oscillations rapidly stopped when extracellular Ca2+ was reduced to nanomolar
      concentrations, revealing their complete dependence on Ca2+ influx. The fact that
      the Ca2+ oscillations were blocked by 1 microM omega-conotoxin, but not by
      nifedipine, at concentrations up to 50 microM, indicated that Ca2+ entered the
      cell via N-type rather than L-type voltage operated Ca2+ channels. Thapsigargin,
      a putative inhibitor of intracellular Ca(2+)-ATPase activity, elevated the
      baseline Ca2+ concentration but had no effect on the occurrence of the
      spontaneous oscillations. This suggests that intracellular Ca2+ pools are not
      involved in the mechanism underlying spontaneous Ca2+ oscillations. This is the
      first report showing spontaneous Ca2+ oscillations mediated by N-type Ca2+
      channels in melanotrope cells.

PMID- 8149405
TI  - Subcellular Ca(2+)-gradients in A7r5 vascular smooth muscle.
AB  - The free calcium concentrations in nucleus ([Ca2+]n) and in cytoplasm ([Ca2+]c)
      of cultured A7r5 smooth muscle were estimated by confocal laser microscopy using
      the Ca(2+)-indicator Indo-1. Upon stimulation with 5 microM vasopressin (AVP) a
      cytosolic Ca2+ gradient was observed whereby the highest increase was observed in
      the subplasmalemmal region. The maximal nuclear Ca2+ concentration ([Ca2+]n)
      attained a lower level than that in the cytoplasm ([Ca2+]c > [Ca2+]n). After the
      initial rise, a second sustained change of the Ca2+ level was found and the
      initial gradient ([Ca2+]c > [Ca2+]n) was preserved. In Ca(2+)-free solution
      containing 2 mM EGTA the maximal [Ca2+]c value after AVP stimulation was
      significantly lower than in the Ca(2+)-containing solution, but it remained
      higher than [Ca2+]n which was the same in both conditions. The initial Ca2+ rise
      was followed by a monoexponential decline. When the influx of Ca2+ through
      voltage-sensitive Ca2+ channels was blocked, the maximal and steady state values
      of [Ca2+]c but not of [Ca2+]n were lower as compared to the values in non-treated
      cells. Preincubation with 10 microM verapamil and 2 mM Ni2+ resulted in initial
      [Ca2+]c and [Ca2+]n rises which were not significantly different from the levels
      found in the absence of Ni2+, but the sustained phase was absent in both
      compartments. The differential effect with [Ca2+]c > [Ca2+]n was not observed if
      1 nM AVP was applied instead of 5 microM AVP. The results indicate that cytosolic
      and nuclear Ca2+ stores behave differently with respect to their dependence on
      the agonist concentration and also with respect to the effect of Ca(2+)-entry
      mechanisms.

PMID- 8149406
TI  - Inositol 1,4,5-trisphosphate receptors in Xenopus laevis oocytes: localization
      and modulation by Ca2+.
AB  - Inositol 1,4,5-trisphosphate receptors (InsP3R) in Xenopus laevis oocytes were
      localized and their regulation by Ca2+ was investigated. Antibodies raised
      against the C-terminal region of the mouse cerebellar InsP3R (cAb) cross-reacted
      with a 255 kD protein in Western blots of Xenopus microsomal membranes.
      Immunolocalization of this protein in cryosections of oocytes revealed diffuse
      staining of the cytoplasm, intense staining of the sub-plasma membrane region of
      the animal hemisphere, and punctate staining in association with the germinal
      vesicle. In the presence of 40 microM free Ca2+, isolated oocyte membranes
      exhibited a high affinity binding site for Ins 1,4,5-P3 (KD = 5nM) and a binding
      capacity of 450 fmol/mg protein. The specific binding capacity of oocyte
      membranes for [3H]-Ins 1,4,5-P3 increased as the level of free Ca2+ present in
      binding assays was raised from < 0.1 nM to 4.0 microM, with an apparent EC50 of
      60 nM. Increasing the concentration of free Ba2+ failed to facilitate [3H]
      Ins1,4,5-P3 binding. Other inositol phosphates competed for Ins1,4,5-P3 binding
      sites with approximate IC50 values of: Ins1,3,4,5-P4 = 79 nM, Ins2,4,5-P3 = 455
      nM and L-Ins1,4,5-P3 = 20 microM. In addition, 150 micrograms/ml (approximately
      12 microM) heparin displaced 50% of bound [3H]-Ins1,4,5-P3, whereas caffeine (10
      mM) had little effect. Functional reconstitution of solubilized InsP3Rs into
      lipid bilayers revealed that Ca2+ was a necessary co-agonist for activation of
      the InsP3R. When InsP3 (5 microM) and Ca2+ (5 microM) were applied together,
      conductance steps were observed. InsP3 or Ca2+ alone had little effect. These
      results suggest that the subcellular organization of InsP3Rs and the facilitation
      of InsP3 binding and channel opening by Ca2+ contribute to the Ins1,4,5-P3
      mediated Ca2+ spikes, waves, and oscillations observed in Xenopus oocytes.

PMID- 8149407
TI  - Fluorescence lifetime imaging of intracellular calcium in COS cells using Quin-2.
AB  - We describe the first fluorescence lifetime images of cells. To demonstrate this
      new capability we measured intracellular images of Ca2+ in COS cells based on the
      Ca(2+)-dependent fluorescence lifetime of Quin-2. Apparent fluorescence lifetimes
      were measured by the phase-modulation method using a gain-modulated image
      intensifier and a slow-scan CCD camera. We describe methods to correct the images
      for photobleaching during acquisition of the data, and to correct for the
      position-dependent response of the image intensifier. The phase angle Quin-2
      images were found to yield lower than expected Ca2+ concentrations, which appears
      to be the result of the formation of fluorescent photoproducts by Quin-2.
      Fluorescence lifetime imaging (FLIM) does not require wavelength-radiometric
      probes and appears to provide new opportunities for chemical imaging of cells.

PMID- 8149408
TI  - The important discrepancy between the apparent affinity observed in Ca2+
      mobilization studies and the Kd measured in binding studies is a consequence of
      the quantal process by which inositol 1,4,5-trisphosphate releases Ca2+ from
      bovine adrenal cortex microsomes.
AB  - Inositol 1,4,5-trisphosphate (InsP3) is a second messenger responsible for Ca2+
      release from a non-mitochondrial intracellular store. An important discrepancy
      has been observed between the affinity measured in binding studies (Kd) and the
      apparent affinity obtained in Ca2+ mobilization studies (EC50). It has been
      proposed that this discrepancy could be due to different experimental conditions
      used for Ca2+ mobilization studies and for InsP3 binding studies. With the
      fluorescent indicator Fura-2, we studied InsP3-induced Ca2+ release activity at 7
      degrees C and at 37 degrees C, in bovine adrenal cortex microsomes. Under both
      conditions, the Ca2+ releasing effect of InsP3 (1 microM) was completed within
      about 2 s, as a result of the quantal process of InsP3 receptor action. The
      apparent affinity (EC50) observed for InsP3-induced Ca2+ release at 7 degrees C
      and at 37 degrees C were 0.64 +/- 0.2 microM and 0.9 +/- 0.2 microM respectively.
      InsP3 degradation studies, at 37 degrees C, indicated that less than 10% of [3H]
      InsP3 was degraded within the first 10 s of incubation. InsP3 association rates
      were evaluated, at low temperature, with increasing concentrations of [3H]-InsP3.
      These kinetic studies revealed a direct relationship between the initial rate of
      association (Vi) and InsP3 concentration. From this relationship, we evaluated
      that the concentration of InsP3 needed to occupy half of the binding sites within
      the first second of incubation was 271 nM. We conclude that the discrepancy
      between Kd and EC50 is related to a kinetic constraint dictated by the quantal
      process by which InsP3 releases Ca2+.

PMID- 8149409
TI  - Enhanced calcium influx by parathyroid hormone in identified Helisoma trivolvis
      snail neurons.
AB  - The modulation of [Ca2+]i by parathyroid hormone (PTH) has been extensively
      studied in vertebrates. The present study examined the effects of PTH on [Ca2+]i
      in isolated invertebrate neurons B5 from buccal ganglia of the pond snail,
      Helisoma trivolvis, utilizing the Fura-2 fluorescence technique. Bovine PTH, bPTH
      (1-84), induced a slow and sustained increase in [Ca2+]i in neurons B5. In
      contrast, the elevation of extracellular K+ concentration from 1.7 mM to 15 mM
      induced a rapid and transient increase in [Ca2+]i. Simultaneous application of 15
      mM KCl and bPTH-(1-84), or application of 15 mM KCl in the presence of bPTH-(1
      84) additively increased [Ca2+]i in neurons B5. An increase in [Ca2+]i in neurons
      B5 was also induced by a PTH agonist [bPTH-(1-34)], but not by a PTH antagonist
      [bPTH-(3-34)]. The absence of calcium, or the presence of lanthanum (2 mM) or
      omega-conotoxin (10 microM), in the bath solution abolished the effect of bPTH-(1
      84) on [Ca2+]i. Furthermore, our results demonstrated that the effect of PTH on
      [Ca2+]i in neurons B5 was not due to the hormonal modulation of voltage-dependent
      Na+ or K+ channels or a Na+/Ca2+ exchanger. The results from this study show that
      PTH can modulate [Ca2+]i in an identified invertebrate neuron mainly by promoting
      extracellular calcium influx via the N-like voltage-dependent calcium channel.

PMID- 8149410
TI  - Fatty acyl-CoA esters induce calcium release from terminal cisternae of skeletal
      muscle.
AB  - The effect of palmitoyl-CoA (PCoA) on Ca2+ fluxes in unfractionated SR,
      longitudinal tubules (LSR) and terminal cisternae (TC) subfractions, obtained
      from rabbit fast-twitch skeletal muscles, was investigated. After MgATP-dependent
      Ca2+ preloading, PCoA released Ca2+ from unfractionated SR and TC, but not from
      LSR. Both the extent and the rate of PCoA-induced Ca2+ release from TC were
      increased in a dose-dependent manner, the half-maximal effect being attained at
      [PCoA] of approximately 6 microM. Ruthenium red, a Ca2+ release channel blocker,
      completely inhibited PCoA-induced Ca2+ release, whereas caffeine, a Ca2+ release
      channel agonist, depleted TC of Ca2+ and prevented the PCoA action. Scatchard
      plot analysis of [3H]-ryanodine binding showed that PCoA increased the affinity
      without affecting Bmax. The action of PCoA was mimicked by a nonhydrolysable
      analog. The present results indicate that PCoA interacts and opens the Ca2+
      release channel (ryanodine receptor) of TC and that the mechanism of action
      involves binding rather than hydrolysis.

PMID- 8149411
TI  - Effects of elevated pressures of inert gases on cytosolic free Ca2+ of cultured
      human neuroblastoma cells stimulated with carbachol: relevance to high pressure
      neurological syndrome.
AB  - Suspended cells of the human neuroblastoma line SK-N-SH were exposed to elevated
      pressures of non-narcotic helium (He) and the narcotic gases nitrogen (N2), and
      argon (Ar) and stimulated with carbachol. He, 18 and 36 atmospheres absolute
      (ATA), equivalent to 544 and 1120 feet of seawater, potentiated the increase in
      [Ca2+]i induced by carbachol, as measured by Fura-2. Carbachol-stimulated
      increases in [Ca2+]i were not significantly altered from values in 1 ATA air by
      either N2 or Ar at the same pressures. The response to carbachol of cells exposed
      to 36 ATA of He and slowly decompressed to 1 ATA was indistinguishable from that
      of cells never exposed to pressure. Thus this pressure-potentiated increase in
      [Ca2+]i is compatible with excitation, is reversible and is not elicited by
      narcotic gases. It was observed, moreover, at pressures encountered by commercial
      deep-sea divers. The High Pressure Neurological Syndrome (HPNS) encountered by
      divers breathing He/O2 mixtures at high pressures, and its known antagonism by
      N2, may be due in part to effects on neuronal [Ca2+]i levels since an increase in
      these would most likely result in an excitatory response.

PMID- 8149412
TI  - Nitric oxide decreases [Ca2+]i in vascular smooth muscle by inhibition of the
      calcium current.
AB  - Endothelium derived relaxing factor (nitric oxide, or NO) activates cytoplasmic
      guanylate cyclase in vascular smooth muscle and decreases vascular tone through
      cGMP-dependent mechanisms that are not yet understood fully. In cultured vascular
      smooth muscle cells (A7r5 cell line) sodium nitroprusside (NP), a vasodilator
      that decomposes into nitric oxide, lowered [Ca2+]i in cells in which [Ca2+]i was
      elevated after depolarization. NP decreased current through voltage-gated calcium
      channels, but did not affect release of calcium from intracellular stores.
      Hemoglobin, a scavenger of NO, reversed the effect of NP on [Ca2+]i and 8-Br
      cGMP, a membrane permeant form of cGMP, mimicked the effect of NP on [Ca2+]i and
      on calcium currents. Thus, the signal transduction mechanism of endothelium
      dependent relaxation of vascular smooth muscle involves a decrease in [Ca2+]i by
      inhibition of Ca2+ entry. Relaxation or vasodilation would then result from
      decreased activity of myosin light chain kinase, in addition to myosin light
      chain dephosphorylation.

PMID- 8149413
TI  - Calcium regulation of skeletal myogenesis. II. Extracellular and cell surface
      effects.
AB  - The process of myoblast fusion during skeletal myogenesis is calcium regulated.
      Suppression of fusion is obtained by lowering medium [Ca2+] and re-initiated by
      raising medium [Ca2+]. Previously, we showed that such changes in medium [Ca2+]
      produced concomitant changes in myoblast [Ca2+] and that a critical cellular
      concentration of calcium must be present in myoblasts for fusion to occur. In
      this study, we report on further investigations on the relationship between
      myoblast [Ca2+] and fusion and also present data which suggest that an outer cell
      surface pool of calcium is involved in the fusion process. Cellular [Ca2+] must
      reach greater than 0.8 pmoles/cell and the medium [Ca2+] must be greater than 0.2
      0.4 mM for myoblast fusion to occur. These conditions do not have a trigger
      effect on the entire myoblast population; instead, myoblast fusion was a dose
      dependent linear response. If medium [Ca2+] was not maintained at 0.9 mM then
      cellular [Ca2+] decreased below a critical 0.8 pmoles/cell nucleus and fusion
      ceased. The cell surface pool of calcium was detected with the calcium antagonist
      lanthanum. A defined culture medium with 0.9 mM Ca2+ was used to maintain cell
      viability, and to prevent precipitation of medium components and changes in
      medium pH with La3+ (0.1 mM). La3+ did not enter the myoblasts as detected by
      electron microscopy, did not inhibit Ca2+ movement into the cells and the
      cellular [Ca2+] was sufficient to promote myoblast fusion. Under these
      conditions, myoblast fusion was inhibited. Morphologically, the fusion-suppressed
      myoblasts resembled those suppressed by lowered medium [Ca2+]. After removal of
      the fusion-block by washing, the myotubes that formed were equivalent to those
      present in unaltered cultures. These results suggest that a La3+ displaceable
      Ca2+ pool exists at the surface of myoblasts which is involved in myoblast
      fusion. Thus, it appears that myoblast fusion is dependent on the continuous
      presence of cell surface calcium and an adequate intracellular Ca2+. An influx of
      calcium alone is not sufficient to promote myotube formation.

PMID- 8149414
TI  - The Ca(2+)-induced permeability transition pore is involved in Ca(2+)-induced
      mitochondrial oscillations. A study on permeabilised Ehrlich ascites tumour
      cells.
AB  - The Ca(2+)-induced permeability transition of the mitochondrial inner membrane
      was studied in digitonin-permeabilized Ehrlich ascites tumour cells respiring on
      succinate in an isotonic medium. Addition of a sufficient amount of Ca2+ to
      induce an efflux of accumulated Ca2+ from mitochondria produced an oscillatory
      state with periodically changing rates of respiration, transmembrane potential,
      delta pH and direction of Ca2+ fluxes. This contrasts with liver mitochondria in
      which only a Ca2+ efflux is induced under these conditions. Addition of traces of
      cyclosporin A (approximately 0.1 nM) damped the oscillations by inhibiting the
      phase in which Ca2+ efflux occurs and promoting the reestablishment of a higher
      transmembrane potential. Efflux was also prevented by addition of ATP or ADP, ATP
      being more potent. Efflux was also inhibited by low concentrations of spermine.
      It is concluded that Ca(2+)-induced oscillations involve the cyclosporin A
      sensitive pore and that the Ehrlich ascites tumour cell mitochondria differ from
      liver mitochondria in being far more sensitive to cyclosporin A and ATP. The
      possible physiological role of the oscillatory state is discussed.

PMID- 8149415
TI  - Importance of arachidonic acid metabolites in regulating ATP-induced calcium
      fluxes in thyroid FRTL-5 cells.
AB  - Stimulating rat thyroid FRTL-5 cells with the purinergic agonist ATP activates
      both the inositol phosphate signal-transduction pathway and the phospholipase A2
      pathway. In the present study we wanted to investigate the possible inter
      relationships between these two systems during ATP-induced changes in
      intracellular free calcium ([Ca2+]i). Pretreatment of Fura-2 loaded cells with 4
      bromophenylacyl, an inhibitor of phospholipase A2, had no effect on the ATP
      induced entry of Ca2+ but inhibited the release of sequestered Ca2+.
      Nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and 5,8,11,14
      eicosatetraynoic acid (ETYA), an inhibitor of cytochrome P-450 enzymes,
      attenuated the ATP-evoked transient increase in [Ca2+]i. Furthermore, the
      capacitative entry of Ca2+ was also attenuated in NDGA- and ETYA-treated cells
      stimulated with ATP. Similar results were obtained using econazole, an inhibitor
      of cytochrome P-450 enzymes. However, treatment of the cells with indomethacin, a
      cyclooxygenase inhibitor, had no effect on the ATP-evoked response in [Ca2+]i. We
      also showed that stimulation of intact or permeabilized FRTL-5 cells with
      arachidonic acid released sequestered calcium. This calcium originated, at least
      in part, from an IP3 sensitive calcium pool. In addition, arachidonic acid
      rapidly acidified the cytosol. The results suggest that metabolism of arachidonic
      acid by a non-cyclooxygenase pathway is of importance in supporting agonist
      induced calcium fluxes evoked via stimulation of the inositol phosphate pathway
      in FRTL-5 cells. Furthermore, arachidonic acid per se may modify agonist-induced
      calcium fluxes in these cells.

PMID- 8149416
TI  - Ca(2+)-mobilising agonists potentiate forskolin- and VIP-stimulated cAMP
      production in human colonic cell line, HT29-cl.19A: role of [Ca2+]i and protein
      kinase C.
AB  - This study has examined the involvement of the Ca(2+)-signalling pathway in the
      regulation of agonist-stimulated cAMP responses in the human colonic
      adenocarcinoma cell line, HT29-cl.19A. The muscarinic agonist, carbachol (CCh)
      stimualted rapid increases in cellular IP3 and cytosolic Ca2+, [Ca2+]i in HT29
      cl.19A cells. These were accompanied by a small but significant increase in basal
      cAMP levels and a marked (3-4-fold) potentiation of both forskolin- (FSK) and VIP
      stimulated cAMP generation. Similar effects were observed with two other Ca(2+)
      mobilising agonists, neurotensin and ATP. The failure of CCh to elicit
      potentiation of adenylate cyclase in broken cell preparations indicated an
      indirect action. Potentiation could be mimicked by the calcium ionophore,
      ionomycin, and thapsigargin and inhibited 70-90% by depleting intracellular Ca2+
      stores suggesting that a rise in [Ca2+]i is the primary mediator of this
      response. In contrast, increasing [Ca2+]i levels to > 500 nM caused a significant
      inhibition of FSK-stimulated cAMP generation. The involvement of protein kinase C
      (PKC) was also assessed. PKC activators phorbol 12,13 dibutyrate (PDB) and 1
      oleoyl-2-acetyl glycerol (OAG) potentiated FSK-stimulated cAMP production by 50
      70% though PDB markedly inhibited the cAMP response to the receptor-mediated cAMP
      agonist, VIP. Neither effect could be elicited by the inactive phorbol ester, 4
      alpha-phorbol, 12,13 didecanoate (PDD). PKC inhibitors staurosporine and H7
      reduced by approximately 25% the CCh-induced potentiation of FSK-stimulated cAMP
      generation. In conclusion, these results suggest that stimulation of the
      phosphoinositidase C pathway in HT29-cl.19A colonocytes induces a 'sensitisation'
      of the adenylate cyclase system resulting in a dramatic amplification of agonist
      stimulated cAMP generation. Increases in [Ca2+]i appear to be an important
      mediator of potentiation though activation of PKC may also play a significant
      role.

PMID- 8149417
TI  - Magnesium-dependent calcium efflux in mammalian heart muscle.
AB  - Extra and intracellular magnesium is involved in the control of myocardial
      calcium movements. Here we report on an increase in cytosolic calcium
      concentration in resting ventricular myocytes due to the withdrawal of
      extracellular magnesium under the condition of a blocked sodium-dependent calcium
      elimination. Evidence for an activation of cellular calcium efflux by
      extracellular magnesium showed experiments in perfused hearts. It is concluded
      that extracellular magnesium can modulate the intracellular free calcium
      concentration of the myocardial cells by its influence on calcium elimination.

PMID- 8149418
TI  - Thapsigargin-induced Ca2+ release from sarcoplasmic reticulum and asolectin
      vesicles.
AB  - Thapsigargin, an inhibitor of several isoforms of the Ca(2+)-ATPase protein, has
      been used in many cell preparations to induce an increase in cytosolic Ca2+
      concentration purportedly by inhibition of the catalytic cycle. We report in this
      paper, that thapsigargin induces rapid Ca2+ release from sarcoplasmic reticulum
      vesicles at concentrations higher than those required to inhibit ATPase activity.
      Thapsigargin also induces a similar concentration-dependent release in Ca(2+)
      loaded asolectin liposomes devoid of any protein. These data suggest that Ca2+
      release induced by micromolar concentrations of thapsigargin is due to an
      ionophoric effect on the lipid membrane.

PMID- 8149419
TI  - The development of a new family of intracellular calcium probes.
AB  - Four new potential fluorescent probes for Ca2+ using the coumarin moiety as a
      fluorophore have been synthesized and their spectral properties and binding
      affinities for Ca2+ determined. The most promising derivative for intracellular
      use, BTC, exhibits an excitation wavelength shift from 462 nm to 401 nm on
      binding Ca2+, with an emission wavelength of 530 nm. The quantum yield of this
      probe increases from 0.07 as the free indicator to 0.12 on binding Ca2+. BTC,
      loaded as its tetraacetoxymethyl ester (AM ester) into mouse myeloma P3X cells,
      responded only when cytoplasmic Ca2+ exceeded typical intracellular calcium
      concentrations. The dye, therefore, appears to be useful in excitatory cells or
      extracellular spaces with intracellular calcium concentrations high enough to
      saturate typical excitation ratio Ca2+ indicators such as Fura-2.

PMID- 8149420
TI  - On-line quantitative coronary analysis in clinical practice: one step closer to
      reality?
AB  - Quantitative coronary analysis is widely used in studies of
      progression/regression and restenosis of coronary lesions. On-line digital
      systems are used in diagnostic coronary angiography, and as a guide in coronary
      interventions. The aim of this investigation was to test the reliability of
      measures obtained with one commercially available on-line equipment. Well
      visualized coronary lesions from patient studies were analyzed for variability in
      single-frame measurement. Procedural factors affecting the consistency of
      measurements were identified by repeated visualization of the same coronary
      lesion with hand- and power-injection of contrast in various positions in the
      field of the image intensifier, and by imaging of steel phantoms in the same
      positions. Steel phantoms closely resembling coronary lesions as encountered in
      practice were visualized in the most favourable radiologic setting compatible
      with clinical situations. Accuracy and precision of measurements were found to be
      worse than reported in validation studies. This may be due to a host of variables
      which may need to be tested in each laboratory performing on-line quantitative
      coronary angiography, when data so obtained are to be used in clinical decision
      making or in research studies.

PMID- 8149421
TI  - Is intravascular ultrasound better than quantitative coronary arteriography to
      assess cardiac allograft arteriopathy?
AB  - Optimal methods to detect and quantify allograft arteriopathy have not been
      established. Both arteriography and intravascular ultrasound have been used to
      evaluate vessel lumen diameter and area and arterial wall thickness in patients
      following cardiac transplantation, although due to the anatomically diffuse
      nature of this disease, neither technique has been accepted as the diagnostic
      "gold standard". To determine the usefulness of quantitative angiography to
      detect transplant-related coronary artery disease compared to intravascular
      ultrasound, 25 patients underwent both procedures following cardiac
      transplantation (20 < 1 year, 5 > 1 year). Lumen diameter and area measurements
      of proximal coronary artery segments were compared using both techniques.
      Overall, lumen diameter and area measurements correlated closely between the two
      procedures, both for the early and late follow-up patients. However, because of
      the ability to characterize changes more precisely in coronary vessel shape and
      wall thickness, intravascular ultrasound offered distinct advantages over routine
      coronary angiography and is probably the technique of choice to evaluate
      allograft arteriopathy.

PMID- 8149422
TI  - Effect of balloon inflation in angiographically normal coronary segments during
      coronary angioscopy: a quantitative angiographic study.
AB  - Visualization of coronary stenoses by coronary angioscopy is facilitated by
      inflating an occlusive cuff located near the distal end of the device to
      temporarily interrupt blood flow. In animal models, this procedure induces
      substantial endothelial denudation. Experimental studies show that endothelial
      denudation may lead to neointimal hyperplasia at the denuded site. This study was
      designed to determine whether angioscopy was associated with significant changes
      in lumen diameter at the site of cuff inflation. We studied 52 consecutive
      patients undergoing coronary angioscopy. We measured with use of quantitative
      edge-detection angiography [computer-assisted evaluation of stenosis and
      restenosis (CAESAR) system] the mean and minimal lumen diameters at the site of
      cuff inflation localized by filming the inflated cuff during angioscopy and at
      control non-instrumented segments on angiograms performed before angioscopy,
      after angioscopy, and at 6 months follow-up. Follow-up angiograms were performed
      in 80% of eligible patients. At follow-up, the mean (3.22 +/- 0.54 mm) and
      minimal (2.76 +/- 0.58 mm) diameters of the segment exposed to the inflated cuff
      were not significantly different from the equivalent values (3.22 +/- 0.58 and
      2.75 +/- 0.61 mm) before angioscopy. No significant changes occurred in the mean
      or minimal diameters of the control segments over the same period. The late
      change (follow-up minus pre-angioscopy) in mean lumen diameter at the cuff
      inflation site (-0.005 +/- 0.18 mm) was not significantly different from that at
      the control site (0.004 +/- 0.20 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149423
TI  - Complete heart block complicating retrograde left ventricular catheterization:
      case report and review.
AB  - Complete heart block (CHB) following retrograde left ventricular catheterization
      is uncommon. We report a case of transient CHB in a patient with severe aortic
      stenosis and bifascicular block on the baseline surface electrocardiogram during
      retrograde left ventricular catheterization. The block resolved spontaneously
      without sequelae. A review of the literature using MedLine was performed and
      recommendations for temporary and permanent pacing are outlined.

PMID- 8149424
TI  - Unusual tear in Inoue balloon during percutaneous balloon mitral valvuloplasty in
      a patient with calcific mitral stenosis.
AB  - An unusual tear in an Inoue balloon during dilatation of calcific mitral stenosis
      is presented and its mechanisms discussed. An abnormal sequence of inflation
      indicates a possible tear.

PMID- 8149425
TI  - Lupus anticoagulant: a potential risk factor for complication following
      percutaneous transluminal coronary angioplasty.
AB  - A patient is described with antiphospholipid antibodies who died approximately 24
      hr after an uncomplicated balloon angioplasty. Since the literature suggests a
      relationship between the presence of antiphospholipid antibodies and thromboses,
      we suggest that these antibodies may be a risk factor for abrupt closure after
      percutaneous transluminal coronary angioplasty.

PMID- 8149426
TI  - Attenuation of hypertensive-induced pulsus alternans by nifedipine and
      nitroglycerin.

PMID- 8149427
TI  - Fundamentals of translesional pressure-flow velocity measurements. Part II.

PMID- 8149428
TI  - Extendable Probe: a modified method.
AB  - We believe our method improves the ease of extending the Probe by using routine
      equipment readily available in the catheterization laboratory. Another method of
      linking the Probe is also described. In addition, if the second method of linking
      the Probe is used, there will be some cost savings as an extra extension wire is
      not required.

PMID- 8149429
TI  - Coronary thrombus: a novel catheter-based approach to treatment.
AB  - The presence of coronary thrombus during intracoronary interventions increases
      the risk of complications during the procedure. We describe a novel approach to
      infusing thrombolytic agents selectively into a coronary artery utilizing a new
      low-profile perfusion balloon. This approach may add a useful new treatment for
      resistant intracoronary thrombi.

PMID- 8149430
TI  - Prolonged intragraft urokinase with a new infusion wire: improved short-term
      results.
AB  - Patients with aged saphenous vein grafts and recurrent symptoms of angina are
      being seen with increasing frequency [Bourassa: J Am Coll Cardiol 17:1081-1083,
      1991]. The treatment of these patients remains a dilemma. Direct balloon
      angioplasty is frequently complicated by distal embolization and early restenosis
      [Aureran and Gruentzig: Am J Cardiol 53:953-954, 1984]. There is evidence that
      thrombus plays a significant role in this occlusive process [Hartmann et al.: J
      Am Coll Cardiol 18:1517-1523, 1991]. Prolonged intragraft urokinase infusion with
      a new multiside hole infusion catheter debulks thrombus and permits balloon
      angioplasty without the usual complications.

PMID- 8149431
TI  - Coronary revascularization directed by results of coronary Doppler flow
      measurements.
AB  - We present a case where Doppler coronary flow velocity and Doppler reserve
      measurement directed the decision to proceed with coronary artery
      revascularization. Measurement of coronary Doppler flow velocity and flow reserve
      can be useful to help evaluate angiographic "intermediate lesions." The following
      case involves an indeterminate lesion. A patient was felt likely to have a high
      grade stenosis which could not be adequately visualized angiographically because
      of overlapping vessels. Largely based on the flow velocity and reserve data, the
      patient was referred for coronary artery bypass grafting.

PMID- 8149432
TI  - Starr-Edwards valve thrombosis detected preoperatively by transesophageal
      echocardiography.
AB  - A 31-year-old woman developed increasing signs of congestive heart failure 15
      years following placement of a mitral Starr-Edwards mechanical valve. A
      preoperative transesophageal echocardiogram (TEE) demonstrated a large,
      obstructive valvular thrombus and the patient underwent successful reoperative
      valve replacement.

PMID- 8149433
TI  - Unique coronary anatomy and pathology.

PMID- 8149434
TI  - Transient cortical blindness after second coronary angiography: is immunological
      mechanism possible?

PMID- 8149435
TI  - A simple technique to cross mitral valve during percutaneous balloon mitral
      valvuloplasty.

PMID- 8149436
TI  - In response to: "Percutaneous left atrial to femoral arterial bypass pumping for
      circulatory support in high-risk coronary angioplasty".

PMID- 8149437
TI  - Comparison of results of intracoronary stenting in patients with unstable vs.
      stable angina.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) has higher complication and
      restenosis rates when performed in the setting of unstable angina. Balloon
      expandable intracoronary stenting is a new technique with the potential to
      improve the results of PTCA. In order to determine whether stenting is associated
      with a poorer outcome in patients with unstable angina, we retrospectively
      examined our experience with the Palmaz-Schatz balloon-expandable intracoronary
      stent in 105 patients. Patients were divided into 2 groups on the basis of
      symptoms at the time of stent insertion: group I (n = 57) had stable angina
      pectoris, and group II (n = 48) had unstable angina defined as pain at rest
      despite antianginal therapy (Braunwald class II, III). Initial (30-d) and final
      (6-mo) success rates were defined as stent insertion without myocardial
      infarction, need for bypass surgery, death, and significant angina. Baseline
      characteristics were similar, although the patients with unstable symptoms were
      older, more likely to be female, and had a higher incidence of postinfarction
      angina. A total of 136 stents were successfully delivered to 97 target sites in
      92% of patients. Major complications occurred in 4 patients (4%) and were due to
      subacute thrombosis in 3 of them. There were no differences in complication rates
      between patients receiving stents electively with stable vs. unstable symptoms
      (2% vs. 6%, p = NS). Six-mo. follow-up status was ascertained in 96% of patients
      and revealed overall clinical success in 83% with angiographic restenosis (> or =
      50% stenosis) in 28% of patients. There were no significant differences between
      groups in rates of restenosis, follow-up angina class, or overall clinical
      success.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149438
TI  - Thoughts about exercise.

PMID- 8149439
TI  - Musculoskeletal problems of performing artists.
AB  - We have reviewed the frequency and variety of rheumatic problems among performing
      artists. For instrumentalists, injuries are related to the type of instrument
      played, the technique used and the effort expended in the quest for excellence.
      For dancers, musculoskeletal problems too reflect technique and effort. We should
      not be surprised at the frequency of these problems. Rheumatologists, as well as
      orthopaedic surgeons, physiotherapists, neurologists and other physicians,
      encounter performing artists as patients. We should be familiar with their
      problems and be able to knowledgeably diagnose and manage them. This may include
      observing the artist during actual performances. How is the instrument being
      held? What is the posture of the artist? What are the comments of the coach or
      teacher. What type of shoes does the ballerina wear? What movements in particular
      cause discomfort? These and similar observations will have direct bearing on the
      musculoskeletal problems of these artists. Published studies have related the
      variety, frequency and disabling nature of performance-related musculoskeletal
      problems. Unfortunately few if any of these are controlled, blinded or
      prospective. We need more and better information. We will want clear information
      about prevalence of problems, better definition of the musculoskeletal ailments,
      classification of the relationship of problems with performance and individual
      biomechanical features, information about response of specific problems to
      interventions, and data about the long-term consequences, if any, of these
      rheumatic problems to the musculoskeletal system. Artists as patients are unique.
      Minor problems can become potentially career-ending disabilities. Making music or
      performing dance may provide us with delightful entertainment but represents a
      source of livelihood to artists. Understanding their medical needs and enabling
      them to continue to perform is the challenge before us.

PMID- 8149440
TI  - Exercise and soft tissue injury.
AB  - Once the almost exclusive domain of the orthopaedic surgeon, sports injuries are
      now being seen with increasing frequency by other specialists, including
      rheumatologists. It is therefore important for rheumatologists to be able to
      diagnose and manage the various musculoskeletal conditions that are associated
      with physical activity. Soft tissue injuries are a very common cause of morbidity
      in both competitive and recreational athletes. Most of these conditions are
      provoked by muscle-tendon overload (or overuse) that is usually the result of
      excessive training or improper training techniques. However, despite an emerging
      literature on the natural history of soft tissue overuse syndromes, relatively
      little is known about the causes, incidence and outcome of many of these
      injuries. Of the methodologically robust epidemiological studies that have been
      done, most have focused on habitual distance runners. In this population, it has
      been reported that the incidence of injury can be as high as 50% or more, and
      that overtraining and the presence of previous injury are the most significant
      predictors of future injury. In other popular forms of exercise, such as walking,
      swimming, cycling, aerobics and racquet sports, injuries are also reported with
      high frequency but, to date, no prospective studies have examined actual
      incidences in these populations, and risk factors for injury in these activities
      remain speculative. Several of the more commonly occurring soft tissue injuries
      (such as rotator cuff tendinitis, lateral and medial epicondylitis, patellar
      tendinitis, the iliotibial band friction syndrome, Achilles tendinitis and
      plantar fasciitis) exemplify the overuse concept and are therefore highlighted in
      this review. The management of these, and most other, exercise-related soft
      tissue injuries is directed towards promptly restoring normal function and
      preventing re-injury.

PMID- 8149441
TI  - Does stress or trauma cause or aggravate rheumatic disease?

PMID- 8149442
TI  - Exercise for arthritis.
AB  - The data available indicate that ROM, strengthening and aerobic conditioning
      exercises are safe for patients with OA, RA or AS, despite earlier concerns that
      exercise might exacerbate joint symptoms or accelerate disease. Less clear are
      the therapeutic benefits of exercise. In patients with OA, stretching,
      strengthening, and aerobic conditioning programmes can improve the deficits
      observed in these patients. The improvements observed generally have been small,
      and the evidence that these individual improvements result in improved overall
      function is minimal. None the less, it is likely that exercise will reduce pain,
      improve endurance for physical activities and improve cardiovascular fitness.
      Study of the long-term effects of exercise in the geriatric population, for
      sustaining independent living and functioning, is critically important for future
      health care and social expenditures. In RA, strengthening and aerobic
      conditioning exercise programmes can increase muscle strength and cardiovascular
      fitness and probably improve physical function as well. Improvements demonstrated
      in patients with RA seem more convincing than those in patients with OA and AS;
      this probably represents their poorer physical status prior to exercising. For
      patients with AS, intensive physiotherapy brings statistically significant short
      term improvements in spinal and hip ROM which are only modestly clinically
      significant. It is possible that spinal mobility exercises decelerate loss of
      mobility over the long term, but controlled studies are needed to confirm this.
      Improvement in respiratory function with exercise appears to be related to
      cardiopulmonary fitness and perhaps to improvements in diaphragmatic respiration
      rather than to changes in thoracic cage mobility. Given the overall safety and
      likely benefits of the described forms of exercise, exercise should be included
      in the overall treatment of patients with OA, RA or AS. Careful patient
      evaluation and education about exercise should be a part of the exercise
      programme.

PMID- 8149443
TI  - Exercise for the low back pain patient.
AB  - As 90% of patients with acute LBP recover within a 2-month period, irrespective
      of the type of treatment received, exercise probably plays little role in
      facilitating recovery from an acute episode of LBP. It may be a very important
      factor in both symptomatic and functional recovery in chronic LBP, as well as an
      integral factor in preventing recurrent injury. The most efficacious exercise
      regimen for treating LBP is currently unknown. Similarly, little is known about
      the efficacy of individual exercises. In certain patients, flexion or extension
      exercises may be inappropriate. A careful history and physical examination,
      observing the movements that cause pain, will assist the physician in tailoring
      the exercise programme to the individual patient to achieve the greatest
      likelihood of success. Communication between the patient, physician and therapist
      is vital to allow continual adjustment of the programme to best meet the
      patient's needs. As improvement occurs, more stressful exercises can be added to
      improve strength, endurance and aerobic fitness. Individualizing the exercise
      programme to the patient's symptoms and communication between the patient,
      therapist and physician lead to greater compliance with the exercise programme
      and a greater likelihood of improved outcome.

PMID- 8149444
TI  - Special problems of the female athlete.
AB  - The number of women of all ages participating in physical activity is
      consistently increasing. Although there are numerous benefits to physical
      activity, specific problems may occur along the various stages of the female
      athlete's life, which need special attention. A remarkably late menarche,
      exaggerated beyond the expected genetic predisposition and a high prevalence of
      abnormal or absent menstrual cycles is seen in athletes, especially in dancers
      and long distance runners. Reproductive system dysfunction is associated with
      multiple factors, of which nutritional intake and caloric balance seem to be of a
      special importance. A high proportion of athletes suffer from pathological eating
      behaviours and there is an overlap between many features of anorexic patients and
      highly active athletes. The pathophysiology seen in most cases is hypo
      oestrogenism due to suppression of the GnRH pulse generator. The mechanism(s)
      causing this reversible hypothalamic dysfunction are yet unknown. Of major
      concern are the skeletal abnormalities, including failure to reach peak bone
      mass, reduced bone density, scoliosis and stress fractures as a result of
      prolonged hypo-oestrogenism. Hormone replacement may be indicated in cases in
      which reduction of exercise or weight gain is not feasible or unsuccessful. Other
      populations that need special precautions are pregnant athletes and older women.

PMID- 8149445
TI  - Perspectives of an orthopaedist team physician.

PMID- 8149446
TI  - Perspectives of a rheumatologist team physician.

PMID- 8149447
TI  - Exercise and rheumatic disease. Perspectives of an Olympic medallist.

PMID- 8149448
TI  - Exercise assessment of arthritic and elderly individuals.
AB  - Exercise testing is now widely used as both a diagnostic tool in the elderly and
      as a means of generating the information necessary to provide them with a valid
      exercise training prescription. An appropriate medical history and physical
      examination prior to exercise testing will allow for the adequate assessment of
      an individual's risk of undergoing an exercise test. Appropriate screening of the
      individual, assessment of risk prior to exercise, and appropriate monitoring
      during and following the exercise test have contributed to the relative safety of
      maximal exercise testing, with statistics indicating roughly one death occurs in
      every 10,000 clinical maximal exercise tests. When designing an exercise test
      protocol for use in the elderly, their reduced exercise capacities, increased
      prevalence of CV disease, and the reason for doing the test must be taken into
      consideration. The Bruce treadmill protocol is the most widely used exercise test
      in populations of all ages; however, because of its relatively high VO2 demands
      in the initial minutes of exercise, it may not be the optimal protocol for the
      elderly. Other alternative protocols including the Naughton and Balke tests may
      be more appropriate, especially when attempting to generate a valid exercise
      prescription. However, the modified Balke protocol, with a constant speed of 2
      miles/h and starting on the level, is probably the best protocol for exercise
      testing in the elderly for the purposes of generating an exercise prescription.
      If individuals are unable to undergo exercise tests on a treadmill, cycle and arm
      ergometer tests provide alternative test modalities, but these have a number of
      inherent problems that must be considered prior to exercise testing. The
      interpretation of an elderly individual's ECG responses during a maximal exercise
      test is intimately related to their risk of having CV disease prior to the
      exercise test, though fewer false-positive tests will be evident because of the
      increased prevalence of CV disease in the elderly.

PMID- 8149449
TI  - Exercise and the immune response.
AB  - The data presented here document that exercise is associated with changes in
      immunological activity as assessed by a variety of in vitro assays. In general,
      these changes appear to be temporally associated with activity and are not
      persistent. In fact, most alterations are probably secondary to exercise-induced
      hormonal changes, with resultant effects on the intravascular composition of
      immunocompetent cells. Thus, changes in lymphocyte trafficking induced by
      hormonal effects lead to relative and absolute differences in cell numbers, which
      may be reflected in in vitro functional assays. These data argue against any
      profound impact of exercise on the immune system, which might impact on overall
      health. Furthermore, there is little information about exercise decreasing the
      number of infectious illnesses or diminishing the likelihood of immunologically
      mediated conditions or malignancies. Nevertheless, these results should not be
      construed as an argument against the tangible health benefits of exercise. The
      changes in life-style which often accompany exercise programmes, as well as the
      documented benefits for cardiovascular health, are reasons enough to support
      these activities.

PMID- 8149450
TI  - Do occupation-related physical factors contribute to arthritis?
AB  - Occupational physical activities over many years can induce osteoarthritis in
      selected joints. Well-studied examples include evidence of osteoarthritis of the
      knees and spine in miners, osteoarthritis of the hip in farmers and increased
      rates of osteoarthritis of otherwise not usually affected upper extremity joints
      in pneumatic drill operators. Occupation-induced osteoarthritis may not be
      limited to these uncommon occupations but may, in fact, account for a large
      proportion of osteoarthritis in the population. Additional studies of this issue,
      which incorporate high-quality ergonomic assessments of occupational physical
      activities, are needed. People with pre-existing arthritis often experience work
      disability, especially when faced with physically demanding jobs in which they
      have little control over the pace or the specific physical demands of their
      labour.

PMID- 8149451
TI  - Physical activity epidemiology as applied to elderly populations.
AB  - Physical activity epidemiological studies provide one of many types of research
      evidence that are necessary to assess the importance of physical activity to
      health. Available epidemiological evidence, when coupled with relevant
      experimental and clinical research, suggests that physical activity has the
      potential to favourably influence the development and progression of a variety of
      chronic diseases and conditions that are a burden to public health. The evidence
      is only beginning to emerge for elderly populations, however, thereby
      highlighting an important void in our scientific knowledge. Attempting to
      increase the level of physical activity of elderly people raises three important
      issues. First, improving adherence to a physically active life-style requires
      assistance of behavioural scientists, either through direct intervention, or
      through research that can help the elderly identify and overcome impediments to
      physical activity. Second, many elderly people have diseases that can limit their
      physical ability, but exercise scientists can assist by prescribing exercise that
      is both efficacious and safe given the level of limitation. Third, the number of
      injuries may increase with increased physical activity in elderly persons.
      Epidemiologists and exercise scientists working in the area of injury control can
      determine which activities are safe at specific levels of physical ability and
      function. To quote one of the originators of exercise physiology, Per Olaf
      Astrand (1992), 'As a consequence of diminished exercise tolerance, a large and
      increasing number of elderly people will be living below, at, or just above
      "thresholds" of physical ability, needing only a minor intercurrent illness to
      render them completely dependent'. Physical activity can help to push back that
      'threshold of physical ability' and thereby improve physical functioning. As
      physical function improves, there is a propensity to perform even greater amounts
      of physical activity that may be essential to the quality and perhaps quantity of
      life for an elderly person.

PMID- 8149452
TI  - Exercise and the musculoskeletal system.
AB  - 1. Normal joints in individuals of all ages may tolerate prolonged and vigorous
      exercise without adverse consequences or accelerated development of OA. 2.
      Individuals who have underlying muscle weakness or imbalance, neurological
      abnormalities, anatomical variances, and who engage in significant amounts of
      exercise that stress the lower extremities, may accelerate the development of OA.
      3. Individuals who have suffered injuries to supporting structures may also be
      susceptible to accelerated development of OA in weight-bearing joints, even
      without increased stress to the joint from exercise. 4. Certain individuals with
      established degenerative or inflammatory arthritis may benefit from supervised
      exercise programmes. 5. Still more information is needed so that physicians can
      identify subjects at risk for the development of OA, advise the millions of
      participants about the beneficial and deleterious effects of regular exercise and
      sports participation, and develop successful rehabilitation programmes for
      injured joints.

PMID- 8149453
TI  - Regio- and stereoselective synthesis of carbocyclic 2',3'-dideoxy-3'-fluoro
      nucleosides as potential antiviral agents.
AB  - The synthesis and antiviral activity of racemic carbocyclic 2',3'-dideoxy-3'
      fluoro nucleosides are reported. Carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides
      were obtained from the 3-fluoro cyclopentane derivative 4, which was prepared by
      two methods. The SN2-displacement of the hydroxyl group of (+/-)-(1 beta, 2
      alpha, 3 beta, 4 beta)-4-acetamido-2-fluoro-3-hydroxycyclopentylmethyl acetate
      (1) with Ph3P-I2 followed by tin hydride reduction afforded the 3-fluoroamino
      alcohol derivative 3. Alternatively, the protected fluoroamino alcohol 3 was
      prepared by regio- and stereoselective bromo-fluorination of cis-4 beta
      acetamidocyclopent-2-enemethyl acetate (5) with hydrogen fluoride-pyridine/N
      bromosuccinimide followed by tin hydride reduction to remove the bromine atom.
      Carbocyclic 2',3'-dideoxy-3'-fluoroguanosine (14) thus obtained was moderately
      active against herpes simplex virus in vitro.

PMID- 8149454
TI  - Marine natural products. XXXII. Absolute configurations of C-4 of the manoalide
      family, biologically active sesterterpenes from the marine sponge Hyrtios erecta.
AB  - Cytotoxic sesterterpenes, manoalide 25-acetals (1a, 1b), seco-manoalide (2), (E)
      neomanoalide (3), (Z)-neomanoalide (4), and heteronemin (6), were isolated from
      the marine sponge Hyrtios erecta (collected at Amami Island, Kagoshima
      Prefecture, Japan) by bioassay-guided separation and the absolute configurations
      of these manoalide family members have been determined. Manoalide 25-acetals (1a,
      1b) were shown to exhibit in vivo antitumor activity and to inhibit the DNA
      relaxing activity of mouse DNA topoisomerase I and the DNA-unknotting activity of
      calf thymus DNA topoisomerase II.

PMID- 8149455
TI  - Chemical transformation of terpenoids. X. Ionophoretic activities of macrocyclic
      lactone epoxides synthesized from geraniol.
AB  - Two coronand-type 18-membered lactone epoxides, i.e., geranyl dimeric lactone
      diepoxide (GL2E2, 10) and tetraepoxide (GL2E4, 11), were synthesized from
      geraniol as diastereomeric mixtures. Among them, GL2E4 (11) was shown to exhibit
      ion-transport activity for Ca2+ ion in the test using a W-07 (liquid-membrane
      type) apparatus and ion-permeation activities for Ca2+ and K+ ions across the
      human erythrocyte membrane. Isolation of six component diastereomers of GL2E4
      (11) [GL2E4-1 (11c), -2 (11d), -3 (11e), -4 (11f), -5 (11g), -6 (11h)], was
      effected by HPLC separation of two diastereomeric tetraepoxides (11a, 11b) which
      were prepared from two diepoxides (GL2E2-1, 10a and GL2E2-2, 10b). The relative
      stereostructures of these diastereomers were determined by a combination of X-ray
      diffraction and 1H-NMR analyses. Among the six diastereomers, S2-symmetrical
      GL2E4-4 (11f) exhibited the strongest ion-transport activity for Ca2+ ion while
      C2-symmetrical GL2E4-6 (11h) exhibited the strongest ion-permeation activity for
      Ca2+ ion across the human erythrocyte membrane.

PMID- 8149456
TI  - Renin inhibitors. III. Synthesis and structure-activity relationships of
      transition-state inhibitors containing dihydroxyethylene isostere at the P1-P1
      site.
AB  - The design, synthesis and structure-activity relationships of transition-state
      inhibitors containing the dihydroxyethylene isostere at the scissile site are
      described. The compounds with (2S,3R,4S)-4-amino-5-cyclohexyl-1-morpholino-2,3
      pentanediol at the P1-P1 site are potent renin inhibitors. (2S,3R,4S)-4-[N-[(2S)
      3-Ethylsulfonyl-2-(1-naphthylmethyl)propiony l]-L- norleucyl]amino-5-cyclohexyl-1
      morpholino-2,3-pentanediol (2) (BW-175), which is the most potent inhibitor
      (IC50: 3.3 nM against human renin) in this series, poorly inhibits cathepsin D
      (IC50: 26000 nM) and pepsin (IC50: > 100000 nM), and thus it is specific for
      renin. Compound 2 contains only one amino acid and showed an oral bioavailability
      of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. The interaction between renin
      and inhibitor 2 is discussed on the basis of molecular modeling studies.

PMID- 8149457
TI  - Isolation and characterization of saponins from Castanospermum australe Cunn. et
      Fraser.
AB  - Three new triterpenoid saponins, their methyl esters designated as castaralesides
      F (1), G (2) and H (3), were isolated from the fresh leaves of Castanospermum
      australe. The structures of these three saponins were elucidated on the basis of
      chemical and spectral data as 3 beta-O-[beta-galactopyranosyl-(1-->4)-beta
      glucuronopyranosyl]-2 beta,23-dihydroxyolean-12-en-28-oic acid; 3 beta-O-[alpha
      rhamnopyranosyl-(1-->4)-beta-galactopyranosyl-(1-->2)-beta - glucurono-pyranosyl]
      2 beta,28-dihydroxyolean-12-ene; and 3 beta-O-[alpha-rhamnopyranosyl-(1-->4)-beta
      xylopyranosyl-(1-->2)-beta- glucuronopyranosyl]-2 beta,28-dihydroxyolean-12-ene.

PMID- 8149458
TI  - Steroidal glycosides from Asclepias fruticosa L.
AB  - Five novel steroidal glycosides 2-6 were isolated from the whole plant of
      Asclepias fruticosa L. (Asclepiadaceae). The structures of these steroidal
      glycosides were determined on the basis of spectral and chemical evidence. All of
      these glycosides contain 2,6-dideoxyhexopyranoses as component sugars and their
      structures were elucidated as polyoxypregnane-type glycosides, which have
      lineolon as the aglycone moiety.

PMID- 8149459
TI  - Lanosterol oligosaccharides from the plants of the subfamily Scilloideae and
      their antitumor-promoter activity.
AB  - Phytochemical studies of the bulbs of Scilla peruviana, Eucomis bicolor,
      Chionodoxa gigantea and C. luciliae gave respectively two new and two known, four
      new and two known, three known, and one new and five known lanosterol
      oligosaccharides. The structures of the new compounds were determined from
      spectroscopic data. A total of 19 lanosterols, including previously isolated
      compounds, were examined for inhibitory activity on 12-O-tetradecanoylphorbol 13
      acetate (TPA)-stimulated 32P incorporation into phospholipids of HeLa cells as
      the primary screening test to find new antitumor-promoter compounds.

PMID- 8149460
TI  - Studies on dissolution tests for soft gelatin capsules. IV. Dissolution test of
      nifedipine soft gelatin capsule containing water soluble vehicles by the rotating
      dialysis cell method.
AB  - The dissolution of oval soft gelatin capsules containing 5 mg of nifedipine
      dissolved in a water soluble vehicle was evaluated by the rotating dialysis cell
      (RDC) method and the paddle (PD) method as described in the Japanese
      Pharmacopoiea (JP) XI. The dissolution pattern of nifedipine obtained by the PD
      method was linear, and almost 100% of the content was dissolved within 7 to 10
      min. The dissolution pattern obtained by the RDC method corresponded to the
      absorption pattern vs. time curve obtained by th oral administration test in
      humans. When the RDC method was performed with the cell containing a buffered
      solution coupled with n-octanol as the dissolution medium, the in vitro
      dissolution pattern best simulated the in vivo absorption pattern.

PMID- 8149461
TI  - Preparation of 6(1),6n-di-O-(tert-butyldimethylsilyl)-cyclomalto-octaoses.
AB  - Four positional isomers of 6(1),6n-di-O-(tert-butyldimethylsilyl)- cyclomalto
      octaose (n = 2-5) were prepared by reaction of cyclomalto-octaose (1, cG8) with
      tert-butyldimethylsilyl chloride in pyridine, and were isolated by high
      performance liquid chromatography. The regiochemical determination of those
      positional isomers was performed by comparison with authentic compounds, prepared
      from 6(1),6n-di-O-trityl-cG8s (n = 2-5).

PMID- 8149462
TI  - Synthesis, lipophilicity studies and antibacterial properties of some novel
      quaternary ammonium salts.
AB  - The synthesis of some novel quaternary ammonium salts, derivatives of 15-phenyl
      decapentanoic acid, is described. Their lipophilicity was estimated applying the
      Hansch-Leo fragmental procedure and measured by means of reversed phase thin
      layer chromatography. All compounds were tested for their antibacterial activity
      against Gram positive and gram negative microorganisms. The less lipophilic
      compounds showed weak activity, mainly against gram positive microorganisms.

PMID- 8149463
TI  - Synthesis and mutagenicity of a new mutagen, 2-amino-1,7,9-trimethylimidazo[4,5
      g]quinoxaline, and its analog.
AB  - A new mutagen, 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (1), isolated
      from beef extract, was synthesized from 3-fluoro-2-methylaniline via an
      intermediate, 2,8-dimethyl-7-methylaminoquinoxaline (7a). Its 2-methylanalog (2)
      was also synthesized from the same intermediate. The synthetic 1 showed the same
      mutagenic activity as the isolated mutagen. However, 2 was non-mutagenic.

PMID- 8149464
TI  - Differential recognition of stereochemically defined base adducts by antibodies
      against anti-benzo[a]pyrene diol-epoxide-modified DNA.
AB  - The configurational isomers of benzo[a]pyrene diol-epoxide exhibit a range of
      reactivity, adduct profiles, genotoxic, mutagenic and tumorigenic responses.
      Whilst the (+)-enantiomer of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy
      7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) is the most potent genotoxic
      species, studies dealing with many critical aspects of BPDE genotoxicity have
      predominantly been done with the racemic mixture of anti-BPDE. By utilizing
      highly sensitive non-competitive immunoassays, we have shown that both polyclonal
      and monoclonal antibodies developed against anti-BPDE-modified DNA exhibit a high
      degree of stereospecific adduct selectivity with 11mer oligodeoxynucleotides
      containing a single well-defined base adduct. The polyclonal antibody (PAb BP1)
      distinctly recognized the highly carcinogenic lesion (+)-anti-BPDE-N2-dG with a
      40-fold preference over the (-)-anti-BPDE-N2-dG adduct. In contrast, the
      monoclonal antibody (MAb 5D2) bound avidly to (-)-anti-BPDE-N2-dG and exhibited
      very little affinity for the (+)-anti-BPDE-N2-dG adduct. The overall sensitivity
      of detection of polyclonal antibodies for adducts in (+/-)-anti-BPDE-modified DNA
      was about 90-fold higher than monoclonal antibodies. Neither antibody showed any
      detectable reactivity with (+)-or (-)-anti-BPDE-N6-dA and with unmodified DNA
      antigens. The distinct preference of antibodies for particular enantiomeric
      adducts was observed in both single and duplexed oligomeric conformations. The
      demonstrated differential interaction of antibodies with the established
      conformations of (+)- and (-)-enantiomer anti-BPDE-DNA adducts (de los Santos et
      al., Biochemistry, 31, 5245-5252, 1992), has significant implications for in
      vitro and in vivo adduct processing and risk assessment biomonitoring studies.

PMID- 8149465
TI  - Characterization of tissue selenium profiles and anticarcinogenic responses in
      rats fed natural sources of selenium-rich products.
AB  - The present report describes the biological effects associated with the feeding
      of three selenium-rich natural products in rats: high-selenium garlic, high
      selenium onion and Brazil nut. The first two are experimental crops cultivated
      with selenium fertilization. Brazil nut is probably the only unadulterated high
      selenium food that is available commercially. Tissue selenium profiles, liver
      glutathione concentrations and mammary cancer inhibition (in the dimethylbenz[a]
      anthracene model) were the endpoints of investigation. Parallel designs were set
      up to compare the three high-selenium products with selenite and
      selenomethionine. Previous studies have shown that treatment with seleno
      methionine resulted in significantly greater tissue selenium accumulation,
      particularly in skeletal muscle, than treatment with selenite. In contrast,
      selenite, but not selenomethionine, induced a modest increase in liver
      glutathione concentrations. The objective was to determine whether the high
      selenium natural products elicited responses that were similar to that of
      selenite or selenomethionine. Our experiments suggested that the high-selenium
      garlic and onion might have some unique attributes. First, their ingestion did
      not lead to an exaggerated accumulation of tissue selenium, a concern that was
      shared by both selenomethionine and Brazil nut. Second, unlike selenite, they did
      not cause any perturbation in glutathione homeostasis. Third, they expressed good
      anticancer activity that was equal to, if not better than, that of selenite. The
      chemical form(s) of selenium present in the high-selenium Allium vegetables will
      be discussed in relation to the manifestation of the above characteristics.

PMID- 8149466
TI  - A comparative study of tamoxifen metabolism in female rat, mouse and human liver
      microsomes.
AB  - The metabolisms of tamoxifen in female rat, mouse and human liver microsomal
      preparations were compared. Rat, mouse and human liver microsomes were incubated
      with tamoxifen in the presence of NADPH and MgCl2 and the metabolites formed were
      analysed by on-line HPLC-electrospray ionization MS. The major metabolites formed
      by rat liver microsomes were 4-hydroxytamoxifen, 4'-hydroxytamoxifen, N
      desmethyltamoxifen and tamoxifen N-oxide. In addition, two epoxide metabolites,
      3,4-epoxytamoxifen and 3',4'-epoxytamoxifen, and their hydrolysed derivatives,
      3,4-dihydrodihydroxytamoxifen and 3',4'-dihydrodihydroxytamoxifen, have been
      identified. The pattern of the main metabolites obtained with human liver
      microsomes resembles qualitatively that of rat liver microsomes. The major
      differences between rat and human liver microsomes were that the amount of
      hydroxylated metabolites were much lower in human and only traces of 3,4
      epoxytamoxifen and the corresponding dihydrodihydroxy derivative were detected.
      No 3',4'-epoxytamoxifen was detected in human liver microsomes. The four major
      metabolites were also formed in much larger amounts and with faster rates of
      formation by mouse liver microsomes, though tamoxifen N-oxide clearly
      predominated in this species. Polar metabolites, 3,4-dihydroxytamoxifen and 4
      hydroxytamoxifen N-oxide, which were undetectable in rat and human, were formed
      in significant amounts in mouse microsomes. As in human microsomes, there was
      only one epoxide metabolite, 3,4-epoxytamoxifen, produced by mouse liver
      microsomes at levels lower than that found in rat. The faster rate of metabolism
      and the production of polar metabolites may indicate the ability of mouse to
      detoxify tamoxifen by rapid elimination compared with rat and human. The
      production of a larger amount of potentially reactive epoxide metabolites in rat
      may be responsible for the liver carcinogenesis in this species.

PMID- 8149467
TI  - Characteristics of a purified dog hepatic microsomal N,O-acyltransferase.
AB  - Dog liver microsomes have at least three different enzymes that are capable of
      the deacylation of amides, N-arylhydroxamic acids and carboxylesters, the
      acyltransfer of N-arylhydroxamic acids and the N-acetylation of arylamines. As
      judged by SDS-PAGE stained with silver nitrate, one of these enzymes was purified
      to homogeneity by sequential treatment with Triton X-100, ion-exchange column
      chromatography, gel filtration and chromatofocusing. The protein was a
      glycoprotein trimer with a subunit weight of approximately 60 kDa. It showed
      microheterogeneity on analytical isoelectric focusing (IEF) in polyacrylamide
      with pls of 5.4-5.6. Following digestion with endoglycosidase H, its subunit
      weight was reduced to approximately 58 kDa, and it appeared to be homogeneous on
      IEF with a pl of approximately 5.6. A monoclonal antibody prepared against this
      enzyme also reacted with the pl 6.0 carboxylesterase of rat liver microsomes, but
      did not react with the other two dog hepatic acyltransferases. Conversely, a
      polyclonal antibody raised against the rat esterase reacted with the dog enzyme.
      The N-terminal sequence of the enzyme was Y-P-S-L-P-P-V-V-D-T-V-Q-G-K-V-, which
      was homologous to the form 1 carboxylesterase of rabbit liver and the pl 6.0
      carboxylesterase of rat liver. Immunohistochemical analyses showed the presence
      of this enzyme in the epithelium of dog liver and urinary bladder, human liver
      and rat liver, esophagus, forestomach, glandular stomach, small and large
      intestines, renal tubules, trachea and prostate and alveolar cells of lung. Since
      this enzyme is present in the urothelium, it may be important for the activation
      of urinary metabolites of carcinogenic arylamines for the initiation of bladder
      carcinogenesis in the dog.

PMID- 8149468
TI  - Cyclopenta[cd]pyrene-induced tumorigenicity, Ki-ras codon 12 mutations and DNA
      adducts in strain A/J mouse lung.
AB  - Cyclopenta[cd]pyrene (CPP) is a ubiquitous cyclopenta-fused polycyclic aromatic
      hydrocarbon. CPP is highly genotoxic in bacterial and mammalian systems inducing
      gene mutations, sister chromatid exchanges and morphological transformation. CPP
      is a mouse skin carcinogen, a mouse skin tumor initiator and induces pulmonary
      tumors in newborn mice. We have examined the tumorigenic activity of CPP in
      strain A/J mice, have determined the formation and persistence of CPP-induced DNA
      adducts in lung tissue, and analyzed the mutational spectrum in the Ki-ras
      oncogene from CPP-induced tumors. CPP dissolved in tricaprylin was administered
      by i.p. injection to male A/J mice (20 mice/dose) at 0, 10, 50, 100 and 200
      mg/kg. Animals were killed 8 months later and the lungs removed, fixed, and
      surface adenomas enumerated. CPP proved to be highly tumorigenic in A/J mice in
      terms of inducing lung adenomas. The observed tumor multiplicities (lung
      adenomas/mouse) were: 97.7 +/- 28.7 at 200 mg/kg, 32.8 +/- 15.4 at 100 mg/kg,
      4.63 +/- 2.11 at 50 mg/kg and 0.58 +/- 0.82 at 10 mg/kg. Tricaprylin-treated
      controls produced 0.60 +/- 0.58 lung adenomas/mouse. Groups of mice treated under
      the same dosing conditions as those in the tumor studies were killed 1, 3, 7, 14
      and 21 days after treatment. The lungs were removed, and the DNA was subjected to
      DNA adduct analysis by the 32P-postlabeling method. Total CPP-DNA adducts in
      mouse lung peaked at day 3 with 5870 amol CPP adducts/micrograms DNA after a
      single dose of 200 mg/kg. DNA adduct levels decreased to 1800 amol CPP
      adducts/micrograms DNA at day 21. Qualitative DNA adduct analysis revealed four
      major adducts and one minor adduct. Co-chromatography of the lung DNA from CPP
      treated mice with calf thymus DNA treated with CPP-3,4-oxide indicated that all
      DNA adducts were oxide derived and comparison with CPP-3,4-oxide-treated
      polydeoxyguanylic acid suggests that almost all of these adducts are CPP-3,4
      oxide-2'-deoxyguanosine adducts. Ki-ras codon 12 mutation analysis of the DNA
      from tumors taken from the 100 and 200 mg/kg CPP dose groups demonstrated the
      following patterns: GGT-->CGT (50%); GGT-->GTT (15%); GGT-->TGT (25%); GGT-->GAT
      (10%). We conclude that CPP is highly tumorigenic in the A/J mouse lung adenoma
      model, being five times more active than benzo[a]pyrene. This is unlike the
      result of CPP as a mouse skin tumorigen or tumor initiator in which CPP is
      considerably less potent than benzo[a]pyrene.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8149469
TI  - Inhibition of thymidine kinase in cultured mammary tumor cells by the
      chemopreventive organoselenium compound, 1,4
      phenylenebis(methylene)selenocyanate.
AB  - To identify mechanisms by which the organoselenium compound 1,4
      phenylenebis(methylene)selenocyanate (p-XSC) mediates its chemopreventive
      activities, we have examined its effects on cell lines derived from breast cancer
      of humans and rats. When log-phase cells were treated with a dose of 1 microM p
      XSC, we observed a significant decrease in thymidine kinase (TK) activity within
      4 h, and reduced thymidine incorporation after 24-48 h. When the dose of p-XSC
      was increased to 2 microM, the decrease in TK was accompanied by a modest, but
      significant, decrease in thymidine incorporation at 4 h, and a greater inhibition
      after 24-48 h. At a dose of > or = 3 microM, we observed a large decrease in TK,
      accompanied by > 70% reduction in thymidine incorporation, as well as decreases
      in mitochondrial activity and cell numbers, all within 4 h. Equal concentrations
      of selenium in the form of Na2SeO3 had no effect on the parameters described
      above. These data suggest that inhibition of thymidine kinase is an early effect
      of p-XSC in cultured breast tumor cells.

PMID- 8149470
TI  - Metabolic activation of N-hydroxy-4-acetylaminobiphenyl by cultured human breast
      epithelial cell line MCF 10A.
AB  - Metabolism and nucleic acid binding of the mammary gland carcinogen N-hydroxy-4
      acetylaminobiphenyl (N-OH-AABP) was investigated using the human mammary
      epithelial cell line MCF 10A. Chromatographic analysis of the ethyl acetate
      extract of the media from cultured MCF 10A after 24 h exposure to N-OH-AABP
      revealed the formation of two metabolites, 4-aminobiphenyl (ABP) and 4
      acetylaminobiphenyl (AABP). Incubation of [3H]N-OH-AABP with calf thymus DNA in
      the presence of the cytosols or microsomes revealed a binding of 0.21 and 2.36
      nmol/mg DNA/mg protein respectively. In contrast to cytosol-mediated binding, the
      microsome-mediated binding of [3H]N-OH-AABP to DNA was inhibited by paraoxon.
      Furthermore, exogenous addition of non-labelled N-hydroxy-4-aminobiphenyl (N-OH
      ABP) to the incubation mixture blocked the binding of [3H]N-OH-AABP to DNA,
      suggesting that the metabolic activation process involves inter-molecular
      transacetylation. Cytosols from MCF 10A also catalyzed acetyl coenzyme A (AcCoA)
      dependent binding of [3H]N-OH-ABP to DNA; the amount of binding was 0.51 nmol/mg
      DNA/mg protein. HPLC of the DNA hydrolysate obtained after incubation of [3H]N-OH
      AABP and [3H]N-OH-ABP with the MCF 10A microsomes and cytosols showed N
      (deoxyguanosin-8-yl)-4-aminobiphenyl (dG-ABP) as the primary adduct, based on the
      mobility of the radioactive peak in comparison with the synthetic standard. 32P
      postlabeling of adducted DNA obtained on incubation with N-OH-ABP or N-OH-AABP
      showed similar adduct profiles, with the major adduct corresponding with the
      bisphospho derivative of dG-ABP and a minor adduct corresponding with N
      (deoxyadenosin-8-yl)-4-aminobiphenyl (dA-ABP). Additionally, the cellular DNA
      isolated from MCF 10A following exposure to N-OH-AABP also revealed a major spot
      corresponding with the dG-ABP derivative. These results suggest that the mammary
      gland carcinogen N-OH-AABP is activated to reactive electrophilic species in the
      target human mammary tissues by acetyl transferase(s) enzyme systems.

PMID- 8149471
TI  - Nitrate, nitrite and volatile N-nitroso compounds in the urine of Schistosoma
      haematobium and Schistosoma mansoni infected patients.
AB  - The present study presents, for the first time, the amounts of nitrate, nitrite
      and volatile N-nitroso compounds in saliva and urine samples of Schistosoma
      haematobium and Schistosoma mansoni infected patients. Mid-morning saliva and 24
      h urine samples were collected from male patients infected with S.haematobium (n
      = 129 saliva and 79 urine samples) and S.mansoni (n = 64 saliva and 65 urine
      samples) and in a comparative control group of healthy individuals (n = 27) from
      the Nile Delta region of Egypt. Saliva samples were analyzed for the presence of
      nitrate and nitrite; while urine samples were analyzed for the presence of
      nitrate, nitrite and volatile N-nitroso compounds. In the control group, N
      nitroso-dimethylamine (NDMA) was detected at concentrations (mean +/- SD) of 0.27
      +/- 0.47 microgram/day. N-Nitrosopiperidine (NPIP; 0.6 microgram/day) and N
      nitrosopyrrolidine (NPYR; 0.4 microgram/day) were also present in one sample.
      S.mansoni infected subjects showed significantly (P < 0.001) higher levels of 2.9
      +/- 2.9 micrograms/day NDMA and a higher frequency of NPIP (in 40/65 samples; 0.4
      +/- 0.3 microgram/day) and NPYR occurrence (in 59/65 samples; 0.9 +/- 0.9
      microgram/day). Significant further increases in the excretion of volatile N
      nitroso compounds were found in S.haematobium-infected patients with mean daily
      excretion of 19.2 +/- 21 micrograms/day NDMA (in all samples; P < 0.001), 1.6 +/-
      2.3 micrograms/day NPIP (in 56/79 samples; P < 0.001) and 1.3 +/- 1.9
      micrograms/day NPYR (in 58/79 samples; P < 0.1). The differences either in
      salivary nitrite/nitrate or in urinary nitrite between the three distinct groups
      were not significant. However, the urinary excretion of nitrate was elevated from
      139 +/- 82 mg/day in the control group to 249 +/- 126 mg/day in S.mansoni
      infected patients (P < 0.001) and to 174 +/- 176 mg/day in S.haematobium infected
      subjects (P < 0.005 in comparison to S.mansoni infected group). These results
      suggest a possible role of N-nitroso compounds in the etiology of schistosome
      associated bladder cancer and imply a partial participation of S.mansoni in the
      multistage process of urinary schistosomiasis-associated bladder carcinogenesis.

PMID- 8149472
TI  - A unique structural feature of rabbit DNA repair methyltransferase as revealed by
      cDNA cloning.
AB  - cDNA encoding rabbit O6-methylguanine-DNA methyltransferase that repairs DNA
      damaged by alkylating agents was isolated, using as a probe a fragment of mouse
      cDNA coding for a region containing the active site of the enzyme. The nucleotide
      sequence of the cDNA revealed that the rabbit methyltransferase is a 181-amino
      acid polypeptide with a mol. wt of 19,385. Expression of the cDNA in a
      methyltransferase-deficient Escherichia coli mutant resulted in appearance of a
      23 kDa polypeptide with methyltransferase activity, and this rendered the E.coli
      cells resistant to N-methyl-N'-nitro-N-nitrosoguanidine, in terms of both cell
      killing and induction of mutation. The rabbit methyltransferase is highly
      homologous to this enzyme in human, mouse, rat and hamster, but is 26-30 amino
      acid residues shorter as compared with methyltransferases in other mammalian
      species. Based on a comparison of the nucleotide sequences for the C-terminal
      regions of these proteins, we propose that a single base substitution, which
      would generate a TGA termination codon, was introduced into the sequence for the
      rabbit enzyme during the process of evolution. Existence of the naturally
      occurring truncated form of methyltransferase suggests that the longer C-terminal
      tails of other mammalian methyltransferases may have no significant role in
      exerting functions of the enzyme in vivo.

PMID- 8149473
TI  - Crocidolite asbestos increased 8-hydroxydeoxyguanosine levels in cellular DNA of
      a human promyelocytic leukemia cell line, HL60.
AB  - Crocidolite, one of the most carcinogenic asbestos fibers, induces the release of
      reactive oxygen species (ROS) from neutrophils and macrophages. Using HPLC
      combined with electrochemical detection, we determined that 8
      hydroxydeoxyguanosine (8OHdG), a molecule typical of mutagenic oxidative DNA
      damage, was induced in the cellular DNA of a human promyelocytic leukemia cell
      line, HL60, incubated with crocidolite. Crocidolite increased 8OHdG in the
      cellular DNA of phorbol myristate acetate (PMA)-differentiated HL60, which
      phagocytosed crocidolite. PMA-differentiated HL60 released ROS spontaneously, as
      determined by ESR with 5,5-dimethylpyrrolone-N-oxide as a spin trap. However, the
      release of ROS from the cell line did not increase after the addition of
      crocidolite. The addition of superoxide dismutase at a sufficient concentration
      to scavenge ROS released from the cell did not inhibit the 8OHdG increase induced
      by crocidolite. Cytochalasin B, which inhibited phagocytosis, did not inhibit the
      release of ROS. However, it inhibited the crocidolite-induced 8OHdG increase by
      48.3%. Contrary to PMA-differentiated HL60, undifferentiated HL60 neither
      phagocytosed crocidolite nor showed a crocidolite-induced increase in 8OHdG
      formation. The 8OHdG increase induced by crocidolite was not correlated with ROS
      release, but with the internalization of crocidolite, suggesting that the
      increase was not due to an increase in ROS release from the cell but was due to
      the conversion of relatively inert ROS to highly reactive ROS, such as hydroxyl
      radicals, by crocidolite that was internalized and close to DNA.

PMID- 8149474
TI  - Adduction of the heterocyclic amine food mutagens IQ and PhIP to mitochondrial
      and nuclear DNA in the liver of Fischer-344 rats.
AB  - The heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogens that form DNA
      adducts. In the present study, we used the 32P-postlabeling method to measure the
      levels of IQ and PhIP adducts in hepatic nuclear and mitochondrial DNA of Fischer
      344 rats given a single dose (100 mg/kg, p.o.) or 10 doses of either carcinogen.
      After a single dose of IQ, adduct levels were > 2-fold higher in hepatic nuclear
      than in mitochondrial DNA; however, after repeated IQ exposure, the levels of
      adducts in nuclear and mitochondrial DNA were not significantly different. In
      contrast, after a single dose of PhIP, there were no significant differences in
      adduct levels in nuclear and mitochondrial DNA; however, after multiple doses of
      PhIP, adduct levels were significantly higher in mitochondrial DNA than in
      nuclear DNA. The percentages of individual IQ or PhIP adducts were different
      between nuclear DNA and mitochondrial DNA, particularly after 10 doses. With IQ,
      the C8-guanine adduct accounted for 72% of the total IQ adduct levels in nuclear
      DNA but only 40% of total adduct levels in mitochondrial DNA. After 10 doses of
      PhIP, the C8-guanine adduct accounted for 48% and 15% of total adduct levels in
      nuclear DNA and mitochondrial DNA respectively. In addition, the percentage of an
      uncharacterized PhIP adduct was 14% in nuclear DNA but < 1% in mitochondrial DNA.
      The percentages of individual adducts were approximately the same 3, 24, 120 and
      240 h after a single dose of either compound, though total IQ and PhIP adduct
      levels appeared to decline over time in both organelles. The significance of IQ
      and PhIP mitochondrial DNA adduction and the influence of distinct heterocyclic
      amine adducts on carcinogenesis merit further investigation.

PMID- 8149475
TI  - Effects on tumor induction, growth, metastasis and histology of concurrent
      administration of putrescine and its metabolizing inhibitor alpha
      difluoromethylornithine in nickel tumorigenesis in soft tissue.
AB  - The effects of putrescine and the inhibitor of its biosynthesis alpha
      difluoromethylornithine (DFMO) on nickel tumorigenesis in soft tissue was
      studied. Three groups of female F-344 rats were injected i.m. with 10 mg of
      nickel subsulfide (NiSS) in the right hind leg, after which one group was
      administered 200 mg/kg body wt of putrescine (i.p.) once a week, and one group
      was administered 0.2% DFMO in the drinking water for 32 weeks until termination.
      The DFMO-treated group exhibited longer tumor induction time, lower tumor growth
      rate and significantly lower metastatic rate, whereas the putrescine-treated
      group exhibited a temporarily higher tumor growth rate than the NiSS-only group.
      Histologically, the putrescine-treated group and especially the DFMO-treated
      group frequently exhibited differentiated sarcomas but the NiSS-only group
      exhibited anaplastic sarcomas. The present study demonstrated that long-term
      administration of DFMO has an inhibitory effect on tumors and metastasis, and
      induces differentiation of tumor cells from anaplastic round cells to well
      differentiated pleomorphic cells in NiSS tumorigenesis in soft tissue.

PMID- 8149476
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is expressed in mouse
      skin in response to tumor-promoting agents and modulates dermal inflammation and
      epidermal dark cell numbers.
AB  - In mouse dorsal skin multistage carcinogenesis models, tumor promotion can be
      mediated by chemical agents, but also by wounding or abrasion of the epidermis,
      suggesting that endogenous growth factors mediate this process. Granulocyte
      macrophage colony-stimulating factor (GM-CSF) is one such factor that has been
      reported to be produced by keratinocytes in vitro, and has been suggested both to
      stimulate keratinocyte proliferation, and also to be a chemoattractant for
      neutrophils and macrophages. In this study we examined the expression and
      function of GM-CSF in mouse skin following the application of tumor-promoting
      agents. Both single and multiple applications of 12-O-tetradecanoylphorbol-13
      acetate (TPA) resulted in accumulation of GM-CSF mRNA in the epidermis. Various
      phorbol and non-phorbol ester tumor promoters were found to induce increases in
      epidermal GM-CSF mRNA levels commensurate with their relative tumor promoting
      capabilities. Fluocinolone acetonide (FA) and tosyl phenylalanine chloromethyl
      ketone (TPCK), inhibitors of tumor promotion, inhibited tumor promoter-mediated
      GM-CSF accumulation, whereas all-trans-retinoic acid (RA) enhanced the TPA
      induced increase. The retinoic acid analogue RO-109359 which, unlike RA, does not
      have tumor promoting activity per se, inhibited the TPA-induced increase in
      epidermal GM-CSF mRNA levels. When an antibody specific to GM-CSF was
      administered prior to TPA, the promoter-induced dermal inflammation and increase
      in epidermal dark cell number were reduced, yet promoter-induced epidermal
      hyperplasia was not. These findings implied that elevation of GM-CSF levels plays
      an important role in chemically-mediated mouse skin tumor promotion and
      principally via effects on promoter-induced inflammation and increased epidermal
      dark cell number.

PMID- 8149477
TI  - DNA adduct formation and repair in hamster and rat tracheas exposed to
      benzo[a]pyrene in organ culture.
AB  - Syrian golden hamsters are much more susceptible than Wistar rats to the
      induction of tracheal tumors by benzo[a]pyrene (B[a]P). To investigate whether
      this difference is reflected in the pattern of DNA adduct induction and removal,
      tracheas from either species were isolated and exposed to B[a]P (5 micrograms/ml)
      in organ culture. At various time-points B[a]P-DNA adducts were quantified by 32P
      postlabeling; unscheduled DNA synthesis (UDS) and cell proliferation were
      determined by [3H]thymidine incorporation during the 18 h before sampling. In an
      induction-repair experiment tracheas were exposed to B[a]P for 2 days, and
      cultured for another 4 days without B[a]P. After 2 days of exposure total B[a]P
      DNA adduct levels were 10 times higher in hamster compared to rat tracheas. In
      hamster tracheas one major adduct was formed (95%), namely the adduct between (+)
      anti-benzo[a]pyrene diolepoxide and deoxyguanosine (BPDE-N2dG). In rat tracheas
      BPDE-N2dG comprised approximately 60% of the total B[a]P-DNA adduct level. The
      other major adduct found in rat tracheas is probably derived from interaction of
      syn-BPDE and deoxyadenosine. During exposure to B[a]P in hamsters the adduct
      level increased to 36 +/- 19 adducts/10(6) nucleotides (add/10(6)n) on day 2. Two
      days after removal of B[a]P the B[a]P-DNA adduct level had decreased to 60% of
      that on day 2; there was no further decrease in the B[a]P-DNA adduct level,
      despite considerable cell proliferation at the end of the 6 day culture period.
      UDS increased during exposure to B[a]P and decreased after removal of B[a]P. In
      rats removal of B[a]P did not lead to a decrease in the B[a]P-DNA adduct level,
      which agreed with the observed absence of UDS. In a second experiment tracheas
      were exposed to B[a]P continuously for 15 days. In hamster tracheas the total
      B[a]P-DNA adduct level increased from 11 +/- 0.7 add/10(6)n after 1 day of
      exposure to 105 +/- 2 add/10(6)n after 15 days; also UDS increased with
      increasing exposure until day 11. Cell proliferation was low at the end of the
      culture period. In rat tracheas no progressive increase in the B[a]P-DNA adduct
      level was seen, UDS was not increased and cell proliferation had increased
      significantly at the end of the exposure period. The extent of adduct induction
      in the trachea of the two species corresponded with the different
      susceptibilities to B[a]P-induced tumor formation.

PMID- 8149478
TI  - Metabolic activation of the food mutagen Trp-P-1 in endothelial cells of heart
      and kidney in cytochrome P450-induced mice.
AB  - Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) is a carcinogen metabolized
      by hepatic cytochrome P4501A (P4501A). This study showed that there was a highly
      selective solvent-resistant binding of radioactive substance in endothelial cells
      of heart and kidney 1 day following injection of [3H]-Trp-P-1 (0.1 or 1.5 mg/kg)
      in NMRI mice treated with the P450-inducing agent beta-naphthoflavone (BNF). In
      the heart, the binding was highest in capillaries and coronary vessels. In the
      kidney, the binding was highest in afferent and efferent arterioles and
      glomerular and peritubular capillaries. A corresponding localization of
      radioactivity did not occur in corn oil-treated mice injected with [3H]-Trp-P-1.
      On incubation of heart and kidney slices with [3H]-Trp-P-1, there was a binding
      of radioactivity in endothelial cells of BNF-treated mice, but not in corn oil
      treated mice. The P4501A inhibitor ellipticine abolished the BNF-induced
      endothelial binding of [3H]-Trp-P-1 in vivo and in vitro, whereas the effects of
      alpha-naphthoflavone were inconsistent. The results indicate an in situ
      metabolism of [3H]-Trp-P-1 to a reactive species, catalysed by a BNF-inducible
      enzyme, possibly P4501A1, in endothelial cells in the heart and kidney. Since
      related heterocyclic amines induce tumors and other lesions in the rodent
      vascular system, the results raise the possibility that Trp-P-1 and other food
      mutagens may play a role in cardiovascular disease.

PMID- 8149479
TI  - Effect of salt-induced mucosal damage and healing on penetration of N-methyl-N'
      nitro-N-nitrosoguanidine to proliferative cells in the gastric mucosa of rats.
AB  - We have studied the effect of gastric exposure to 4.5 M NaCl on penetration of a
      carcinogen, N-[3H]methyl-N'-nitro-N-nitrosoguanidine (3H-MNNG) from the gastric
      lumen to proliferative cells in the gastric mucosa of Wistar rats at different
      time intervals after salt exposure. Cells in S-phase were labeled by
      incorporation of bromodeoxyuridine. Cells in S-phase labeled with 3H-MNNG (double
      labeled cells) are the cell population at risk of N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG)-induced gastric carcinogenesis. Ten minutes after salt
      damage the average percentage S-phase cells labeled with 3H-MNNG in pylorus was
      significantly decreased compared to control (1.2 +/- 0.6 and 9.5 +/- 0.7). Ten
      minutes after salt exposure a marked increase in gastric mucosal blood flow and
      leakage of fluid from the mucosa into the gastric lumen were observed, and the
      damaged gastric mucosa was covered by a thick mucoid layer. These factors may
      contribute to the reduced 3H-MNNG penetration into mucosa immediately after
      damage. Two hours after salt exposure the number of double-labeled cells (8.6 +/-
      3.7/mm) and percentage S-phase cells labeled with 3H-MNNG (10.4 +/- 3.1) in
      pylorus did not differ from control (6.1 +/- 0.9/mm and 9.5 +/- 0.7). Twelve and
      24 h after salt exposure the number of double-labeled cells (79.6 +/- 13.4/mm and
      32.4 +/- 2.4/mm) and the percentage S-phase cells labeled with 3H-MNNG (29.7 +/-
      2.8 and 18.9 +/- 1.3) in pylorus were significantly increased compared to
      control. Increased number of S-phase cells, a higher location of the
      proliferative zone in the glandular layer were observed 12-24 h after salt
      exposure and increased permeability of the mucosa to carcinogen was observed 12 h
      after salt exposure. These factors explain the increased number of double-labeled
      cells and the increased penetration of carcinogens to the proliferative cells,
      and may contribute to explain the previously described cocarcinogenic effect of
      salt on gastric carcinogenesis.

PMID- 8149480
TI  - Characterization of neutral metabolites of benzo[a]pyrene in urine from germfree
      rats.
AB  - [14C]Benzo[a]pyrene (BP) was administered to male germfree rats. Urinary
      metabolites, constituting 9% of the administered radioactivity, were fractionated
      by lipophilic ion exchange chromatography. More than 80% of the urinary
      metabolites were conjugated, while neutral metabolites constituted 13-18%. The
      latter group was characterized by reversed-phase HPLC, ultraviolet spectrometry
      (UV) and gas chromatography/mass spectrometry (GC/MS). Relative quantities of BP
      metabolites were estimated from the distribution of radioactivity upon HPLC
      fractionation. Some coeluted peaks were further quantitated from the total ion
      current chromatograms obtained in the GC/MS analysis. Two 7,8,9,10-tetrols which
      might be produced from the ultimate carcinogen r-7-t-8-dihydroxy-t-9,10-oxy
      7,8,9,10-tetrahydro-BP (anti-7,8-diol-9,10-epoxide) were detected at trace levels
      and indicated to be the r-7-t-8,9-c-10-(7,10/8,9-) and r-7-t-8,9,10-(7/8,9,10-)
      isomers. A trans-11,12-dihydrodiol was characterized as a major metabolite, while
      a trans-7,8-dihydrodiol was present at trace levels. Three additional
      quantitatively important metabolites were identified as isomeric trihydroxy-BPs.
      Two metabolites coeluting with BP quinones on HPLC were detected with relatively
      high abundance and tentatively identified as carboxylic methyl ester derivatives
      of BP quinones. Three quinones were detected with 1,6-, 3,6- and 6,12
      substitutions. The 6,12- and 11,12-dihydroxy-BPs were also found at trace levels.
      A group of quinone-like metabolites were tentatively identified as trioxo-BPs. No
      monohydroxy-BP was detected in the neutral fraction of the urine extract. The
      time course of excretion was also studied and found to differ between individual
      metabolites.

PMID- 8149481
TI  - Inhibition of gap junctional intercellular communication in Syrian hamster embryo
      cells by TPA, retinoic acid and DDT.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA), trans-retinoic acid (RA) and DDT
      inhibit gap junctional intercellular communication in Syrian hamster embryo (SHE)
      cells. The inhibition is rapid and takes place within minutes. Northern blot
      analysis shows that SHE cells express connexin 43 and that exposure to these
      compounds for up to 20 h has no effect on connexin 43 mRNA level. Immune
      cytochemistry shows that the connexon structures in SHE cells are scattered over
      the cell, and not confined to the cell-cell boundaries as is the case in the rat
      liver epithelial cell line IAR20. RA and TPA induce the disappearance of the
      connexon structures in parallel to the induced inhibition of communication in SHE
      cells. The disappearance of the connexon spots takes place with no apparent
      effect on the cellular content of connexin protein measured by immunoblotting,
      and is probably caused by disaggregation of the connexon structures rather than
      disappearance or degradation of the connexin protein. DDT shows little or no
      apparent effect on connexin immunostaining in SHE cells, indicating a different
      mechanism of action. In the IAR20 cells, exposure to TPA and RA also results in
      loss of immunostainable connexon structures while exposure to DDT results in
      relocalization of the connexons away from the cell-cell borders. Immunoblotting
      of connexin 43 in SHE cells results in three major bands with apparent mol. wts
      of 40-50 kDa where the two higher mol. wt bands represent phosphorylated connexin
      43 protein. Exposure of the cells to the communication inhibiting compounds
      results in reduction or loss of the highest mol. wt phosphorylated band,
      indicating a relation between a specific connexin phosphorylation and aggregation
      of connexin 43 protein to functional communicating gap junctions. The results
      suggest the presence of various post-transcriptional control mechanisms in the
      regulation of connexin function which are vulnerable to exogenous stimuli.

PMID- 8149482
TI  - Permissivity for methotrexate-induced DHFR gene amplification correlates with the
      metastatic potential of rat adenocarcinoma cells.
AB  - During selection for methotrexate (MTX) resistance the metastatic subclone
      BSp73ASML of a spontaneous rat adenocarcinoma and a metastatic transfectant
      containing the metastogene META-1 underwent amplification of the dihydrofolate
      reductase (DHFR) gene at accelerated rates in contrast to non-metastatic but
      closely related BSp73AS cells. A four log increase in MTX resistance was
      associated with a 16-fold amplification and increased expression of the DHFR
      gene. The capacity for gene amplification in metastatic BSp73ASML cells was
      correlated with a deletion in the p53 gene and enhanced expression of the
      oncogene c-myc due to a 10-fold amplification of the myc gene. Increased
      expression of Ki-ras and c-raf in the non-metastatic BSp73AS cells seems to
      confer tumorigenicity but not permissivity for gene amplification.

PMID- 8149483
TI  - Retinoic acid nuclear receptors and tumor promotion: decreased expression of
      retinoic acid nuclear receptors by the tumor promoter 12-O-tetradecanoylphorbol
      13-acetate.
AB  - During studies to determine the mechanism of tumor promotion by 12-O
      tetradecanoylphorbol-13-acetate (TPA), we found that TPA downregulates mouse
      epidermal retinoic acid nuclear receptors (RAR), a superfamily of nuclear
      steroid/thyroid receptors implicated in mediating effects of retinoic acid (RA).
      Application of TPA to mouse skin decreased the binding of [3H]RA to RAR from
      mouse epidermal nuclear extracts. In this experiment, 20 nmol of TPA was applied
      to mouse skin and 3.5 h later binding of [3H]RA to RAR was analyzed by
      chromatography on a size-exclusion column. TPA treatment resulted in an
      approximately 67% decrease in the specific binding of [3H]RA to RAR. In a more
      detailed time course, application of 20 nmol of TPA to mouse skin led to 20, 36,
      92 and 0% decrease in the binding of [3H]RA to mouse epidermal RAR at 2, 4, 12
      and 72 h after treatment respectively. Okadaic acid, an inhibitor of protein
      phosphatases 1 and 2A but a mouse skin tumor promoter, also inhibited the binding
      of RA to RAR. RAR alpha and RAR gamma, but not RAR beta mRNA, could be detected
      in mouse epidermis. In addition, RA nuclear receptor RXR alpha was also expressed
      in the mouse epidermis. As determined by Northern blot analysis of total as well
      as poly(A)+ RNA, application of 10 nmol of TPA to mouse skin led to decreased
      expression of RAR alpha, RAR gamma and RXR alpha mRNA at 3.5 h after treatment.
      The effect of TPA on the attenuation of RAR expression was specific. Specific
      binding of RA to RAR was decreased when TPA-induced expression of the c-fos, c
      jun and ornithine decarboxylase gene was increased. Downregulation of RAR(s) may
      be an essential component of the mechanism of mouse skin tumor promotion.

PMID- 8149484
TI  - Involvement of protein kinase C in the transcriptional regulation of 12-O
      tetradecanoylphorbol-13-acetate-inducible genes modulated by AP-1 or non-AP-1
      transacting factors.
AB  - The involvement of protein kinase C (PKC), a 12-O-tetradecanoylphorbol-13-acetate
      (TPA) receptor, in the transcriptional regulation of TPA-inducible genes was
      determined. Expression plasmids harboring full-length or kinase domain of PKC
      alpha and PKC delta (PKC alpha K and PKC delta K) were constructed. Transient
      transfection of PKC alpha K and PKC delta K into COS cells resulted in
      approximately 20- and 16-fold increase in phospholipid-, calcium-independent
      protein kinase activity. To determine the effects of overexpression of PKC alpha
      K and PKC delta K on the AP-1-mediated TPA-inducible genes, we transfected into
      COS cells the PKC alpha K or PKC delta K expression plasmids with collagenase
      chloramphenicol acetyltransferase (CAT) reporter construct containing one TPA
      responsive element (TRE), or a construct containing five synthetic TRE linked to
      a thymidine kinase promoter. PKC alpha K or PKC delta K overexpression resulted
      in a comparable increase (approximately 4-fold) in CAT activity. However, CAT
      activity was not increased after transfection of PKC constructs with non-TPA
      responsive thyroid hormone responsive elements CAT construct (delta MTV-TyRE
      pCAT). We also found that deletion of the AP-1-like motif in the SV40 promoter
      abolished the PKC alpha K or PKC delta K-induced activity of luciferase (luc)
      reporter constructs. Overexpression of full-length PKC delta in COS cells also
      increased the activity of the CAT construct with TRE after TPA treatment. We
      determined the effects of overexpression of PKC alpha K and PKC delta K on
      transcription of the ornithine decarboxylase (ODC) gene, which has a non-AP-1
      TRE. Cotransfection of PKC alpha K or PKC delta K expression plasmids with a TPA
      inducible ODC luc construct (-72/+130-ODC-luc) into HeLa cells resulted in an
      increased luc activity. These results indicate that both PKC alpha (calcium
      dependent) and PKC delta (calcium independent) may mediate the transcription of
      TPA-inducible genes through both AP-1 and non-AP-1 sequences.

PMID- 8149485
TI  - Mutagenicity of butadiene and its epoxide metabolites: I. Mutagenic potential of
      1,2-epoxybutene, 1,2,3,4-diepoxybutane and 3,4-epoxy-1,2-butanediol in cultured
      human lymphoblasts.
AB  - The mutagenic potential of the epoxide metabolites of butadiene (BD) was measured
      at the tk and hprt loci in TK6 human lymphoblastoid cells. TK6 cells were exposed
      for 24 h to 0-400 microM 1,2-epoxybutene (EB), 0-800 microM 3,4-epoxy-1,2
      butanediol (EBD), or 0-6 microM 1,2,3,4-diepoxybutane (DEB). Treated cells were
      allowed to grow for several days and then seeded in medium containing either 6
      thioguanine or trifluorothymidine to select for hprt- or tk-/- mutants,
      respectively. All three metabolites were mutagenic at both loci, with DEB
      exhibiting activity at concentrations approximately 100-fold lower than EB or
      EBD. At the hprt locus, an induced mutation frequency of 5 x 10(-6)
      (approximately twice background hprt- frequency) was produced by treatment with
      3.5 microM DEB, 150 microM EB and 450 microM EBD. At the tk locus, a similar
      increase in mutation frequency (total tk-/- frequency) was produced by treatment
      with 1.0 microM DEB, 100 microM EB and 350 microM EBD. Each epoxide tested was
      capable of inducing slow growth tk-/- mutants. This mutant phenotype, as shown
      previously by others, results from large alterations in the tk region which
      completely remove the active tk allele. In addition, Southern blot analysis
      revealed that approximately half of DEB-induced hprt- mutants displayed loss of
      wild-type hprt restriction fragments. No statistically significant increase in
      the fraction of hprt deletions among EB mutants was observed. The ability of DEB
      to induce deletions may be related to its ability to form DNA-DNA and DNA-protein
      cross-links.

PMID- 8149486
TI  - Mutagenicity of butadiene and its epoxide metabolites: II. Mutational spectra of
      butadiene, 1,2-epoxybutene and diepoxybutane at the hprt locus in splenic T cells
      from exposed B6C3F1 mice.
AB  - The mutagenic potential and mutational spectra of butadiene (BD), 1,2-epoxybutene
      (EB), and diepoxybutane (DEB) were determined in splenic T cells from exposed
      B6C3F1 mice. Mice exposed by inhalation to 625 p.p.m. BD for 2 weeks displayed an
      average hprt- mutation frequency of 6.2 x 10(-6) compared to 1.2 x 10(-6) in
      controls. Mice were also given three daily i.p. doses of 60, 80 and 100 mg EB/kg
      or 7, 14 and 21 mg DEB/kg. Average hprt- frequencies of 5.4 x 10(-6), 4.1 x 10(
      6) and 8.6 x 10(-6) were seen in the EB groups, respectively, while average
      frequencies of 4.6 x 10(-6), 9.4 x 10(-6) and 13 x 10(-6) were seen in the DEB
      groups. DNA sequencing revealed that approximately half of the mutations induced
      in vivo by BD, EB and DEB were frameshift mutations. A +1 frameshift 'hotspot' in
      six consecutive guanine bases in exon 3 was observed with all three compounds.
      The remaining mutations produced by BD, EB and DEB were transition and
      transversion mutations at both AT and GC base pairs. Base pair substitutions
      induced by BD were biased in favor of mutation at AT base pairs. The mutational
      spectra produced by BD, EB and DEB were very similar to that observed previously
      with ethylene oxide, suggesting that these epoxide agents may be working through
      a similar mutagenic mechanism.

PMID- 8149487
TI  - Co-expression of human CYP1A1 and a human analog of cytochrome P450-EF in
      response to 2,3,7,8-tetrachloro-dibenzo-p-dioxin in the human mammary carcinoma
      derived MCF-7 cells.
AB  - Cultured human mammary carcinoma (MCF-7) cells exhibited constitutive cytochrome
      P450-dependent metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) (45-75 pmol/mg
      microsomal protein). Exposure of the cells to 2,3,7,8-tetrachloro-dibenzo-p
      dioxin (TCDD), which is known to induce CYP1A1, not only resulted in a 30-fold
      increase in the total microsomal metabolism of DMBA but produced substantial
      differences in the distribution of DMBA metabolites formed. This suggested that
      different cytochrome P450 (P450) forms predominated in untreated and induced
      cells. Comparative studies with TCDD-induced human hepatoblastoma (HepG2) and
      skin cell carcinoma (SCC-13) cells and also recombinantly expressed human CYP1A1,
      confirmed that the DMBA-metabolite profile in TCDD-induced MCF-7 cells was that
      of human CYP1A1. This distribution, however, differed substantially from the
      regioselectivity of rat CYP1A1 and mouse Cyp1a-1. Rabbit antibodies to rat CYP1A1
      completely inhibited the DMBA-metabolizing activity of TCDD-induced MCF-7 cells
      but had no inhibitory effect on constitutive DMBA metabolism which was, however,
      completely inhibited by chicken antibodies to the novel P450 in mouse embryo
      fibroblasts (P450-EF). Anti-P450-EF inhibited only 10% of the DMBA-metabolizing
      activity in the TCDD-induced MCF-7 cell microsomes. Microsomes from untreated MCF
      7 cells expressed a 52 kDa protein that was immunodetectable by rabbit anti-P450
      EF and failed to express immunodetectable levels of human CYP1A1. DMBA
      metabolism, therefore, switches from P450-EF in uninduced microsomes to CYP1A1 in
      TCDD-induced microsomes. The mobility of the P450-EF-like protein in MCF-7 cells
      was higher than that of P450-EF from C3H/10T1/2CL8 (10T1/2) cells (55 kDa). The
      52 kDa protein from MCF-7 cells was induced approximately 8-fold by TCDD while
      CYP1A1 immunodetectable protein was increased to much higher levels. The SCC-13
      cell line exhibited a similar pattern of expression of a 52 kDa P450-EF-like
      protein and CYP1A1. HepG2 cells expressed the highest levels of CYP1A1 in
      response to TCDD without expression of the 52 kDa protein.

PMID- 8149488
TI  - Occurrence of the nitrosamide precursor pyrrolidin-(2)-one in food and tobacco.
AB  - Pyrrolidinone was identified in food and tobacco samples by gas chromatography
      combined with NO-specific chemiluminescence detection (TEA). Up to 77 mg/kg
      pyrrolidinone were detected in cocoa powders, coffee, coffee surrogates, dried
      vegetables and tobacco leaves. When treated with excess nitrite under acidic
      conditions, N-nitrosopyrrolidinone was formed in concentrations up to 44 mg/kg.
      The nitrosation characteristics of pyrrolidinone indicate its possible conversion
      to nitrosopyrrolidinone under conditions of the gastric tract.

PMID- 8149489
TI  - Epoxide reductase activity of mammalian liver cytosols and aldehyde oxidase.
AB  - The present study provides the first evidence that a mammalian liver cytosolic
      enzyme, aldehyde oxidase, has an ability to reduce arene oxides to the parent
      hydrocarbons under anaerobic conditions. The comparative ability of rabbit liver
      preparations to reduce arene oxides was examined using naphthalene 1,2-oxide and
      benzo[a]pyrene 4,5-oxide as substrates. The liver cytosol with an electron donor
      of aldehyde oxidase exhibited much higher epoxide reductase activity compared
      with the liver microsomes with NADPH and FAD. The cytosolic activity was
      sensitive to inhibitors of aldehyde oxidase. Purified rabbit liver aldehyde
      oxidase also exhibited a significant epoxide reductase activity in the presence
      of its electron donor. Apparent Km and Vmax values of the enzyme were 426 microM
      and 323 nmol/min/mg protein for naphthalene 1,2-oxide and 255 microM and 100
      nmol/min/mg protein for benzo[a]pyrene 4,5-oxide respectively. However, no
      epoxide reduction by the enzyme or by the liver cytosol was detected in olefin
      epoxides such as styrene oxide and trans-stilbene oxide. Similar results were
      obtained with rat liver preparations. However, the epoxide reductase activity of
      cytosol and aldehyde oxidase from rat liver was considerably lower than that of
      the rabbit liver preparations. In hamsters, mice and guinea-pigs, liver cytosols
      with an electron donor of aldehyde oxidase as well as liver microsomes with NADPH
      exhibited a significant epoxide reductase activity toward naphthalene 1,2-oxide.
      However, no epoxide reduction was observed with dog liver cytosol. Administration
      of sodium tungstate to rats depleted liver cytosolic reductase activity and
      sodium molybdate treatment resulted in partial restoration of the activity,
      supporting the view that the epoxide reductase activity observed in the liver
      cytosol mainly originates from aldehyde oxidase.

PMID- 8149490
TI  - Increased poly(ADP-ribose) polymerase activity during repair of (+/-)-anti
      benzo[a]pyrene diolepoxide-induced DNA damage in human peripheral blood
      lymphocytes in vitro.
AB  - Poly(ADP-ribose) polymerase, which catalyzes the formation of poly(ADP-ribose)
      polymers, is an enzyme involved in cell proliferation, differentiation and
      transformation as well as in recovery from DNA damage. Poly(ADP-ribose) polymers
      are rapidly synthesized from the ADP-ribose moieties from intracellular NAD+,
      which, as a consequence, is depleted. It has been shown that DNA strand breaks
      are required for enzyme activation and it is suggested that one of the functions
      of poly(ADP-ribosylation) is to improve accessibility of damaged sites to other
      DNA repair enzymes. The aim of this study was to investigate whether poly(ADP
      ribosylation) is involved in repair of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10
      alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene [(+/-)-anti-BPDE]-induced DNA
      damage in human lymphocytes in vitro. Results show that (+/-)-anti-BPDE is
      capable of inducing poly(ADP-ribosylation), NAD+ depletion and inhibition of
      proliferation in phytohemagglutinin-stimulated human peripheral blood
      lymphocytes. Also, repair of (+/-)-anti-BPDE induced DNA damage was confirmed by
      both unscheduled DNA synthesis and (+/-)-anti-BPDE-deoxyguanosine adduct removal.
      Based on these findings, it is concluded that poly(ADP-ribosylation) is involved
      in (+/-)-anti-BPDE-induced DNA repair in these cells. In addition, these results
      confirm the possible relation between poly(ADP-ribosylation), NAD+ depletion and
      inhibition of proliferation, after induction of DNA damage.

PMID- 8149491
TI  - Inductions of oxidative DNA damage and mesothelioma by crocidolite, with special
      reference to the presence of iron inside and outside of asbestos fiber.
AB  - Inductions of oxidative DNA damage (oh8dG) in vitro and peritoneal mesothelioma
      in rats (F344, female) were compared between crocidolite (CR) and de-ironized
      crocidolite [DCR, washed by HCl and ethylenediamine tetraacetic acid (EDTA)] to
      verify the hypothesis that reactive oxygen species contribute to carcinogenesis,
      focusing on the role of iron present inside or outside of the CR. The yield of
      oh8dG was 14.6 oh8dG/10(5)dG in CR and 30.2 in DCR under simple incubation with
      DNA. In the incubation systems added several chemicals and H2O2, DCR induced
      higher levels of oh8dG than CR. Especially, the addition of Fe2O3 and H2O2 to DCR
      increased oh8dG in DNA depending on the Fe2O3 concentration, however, this
      tendency was not observed in the same system of CR. Surprisingly, 7 out of 10
      rats died within 2 days after the injection of 10 mg of Fe2O3 following the DCR
      injection (5 mg/rat), showing necroses of hepatocytes from the surface of each
      lobe where CR and Fe2O3 particles had been deposited together. There was no death
      in other groups of rats. One year after the i.p. injection of CR (5 mg/rat,
      single injection), mesotheliomas were found in all rats administered DCR and
      Fe2O3 (2 mg/rat, once a week, for 35 weeks), in 4 rats of DCR alone (n = 10), in
      5 rats of CR alone (n = 10) and in none of the rats administered Fe2O3 alone (n =
      10). Therefore, present results indicate that the induction of oxidative DNA
      damage changed even when the same type of asbestos was washed by chemical
      treatment, and Fe2O3 promoted the development of mesothelioma which was induced
      by DCR.

PMID- 8149492
TI  - Effect of alpha Ni3S2 on arachidonic acid metabolites in cultured human lung
      cells (L132 cell line).
AB  - Our previous investigations have shown evidence of an interaction between alpha
      Ni3S2 and membranous and cellular lipids of lung cells with a significant
      increase in the linoleic, linolenic and arachidonic acid pool. The present work
      is designed to follow the metabolic fate of arachidonic acid in alpha Ni3S2
      exposed human embryonic pulmonary epithelial cells (L132) in culture (50 microM
      alpha Ni3S2 for 3 days). The metabolites of arachidonic acid were assessed by
      HPLC determination coupled with UV or electrochemical detection. We determined
      malondialdehyde (MDA), hydroxyeicosatetraenoic acid (HETE), leukotrienes (LT) and
      reduced glutathione (GSH). In exposed cells we observed a significant increase of
      MDA, which is a breakdown product of lipid peroxidation. In addition, we noted
      significant increases of 5-HETE and 15-HETE in L132 cells resulting from the
      enzymatic reduction of 5-HPETE and 15-HPETE respectively. There was also a
      simultaneous decrease of GSH--confirmed by a strong decrease of GSH in exposed
      cells with respect to controls. 5-HPETE is furthermore converted to epoxides such
      as leukotriene A4 and we also quantified in exposed cells a significant increase
      of its subsequent catabolites LTB4, LTC4 and LTE4. These investigations show
      clearly that exposure of L132 cells to alpha Ni3S2 enhances lipid peroxidation
      based upon direct measurements of MDA and other metabolites of arachidonic acid.
      This lipid peroxidation is an autocatalytic free-radical process and could be
      responsible for DNA damage.

PMID- 8149493
TI  - Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in rats
      given chlorophyllin: dose-response and time-course studies in the liver and
      colon.
AB  - Chlorophyllin (CHL), a water-soluble salt of chlorophyll, has been shown to
      inhibit 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in vitro by a
      mechanism that involves molecular complex formation with the carcinogen. Based on
      this mechanism, rats weighing approximately 160 g were given 10 mumol (100
      microCi) IQ or IQ plus 20, 200 or 1000 mumol CHL by single oral gavage. Six hours
      after dosing, CHL produced dose-related inhibition of IQ-DNA binding in three
      target organs for carcinogenesis, namely, the small intestine, large intestine
      and liver. In the latter tissues, > 80% inhibition was detected at the highest
      CHL dose tested, while IQ-DNA binding levels in the small intestine were reduced
      to below the limit of detection. Co-injection of CHL and IQ into ligated sections
      of small intestine inhibited the absorption of IQ in a dose-related manner, such
      that the highest dose of CHL almost completely blocked carcinogen uptake.
      Finally, rats given CHL by gavage at time 0 h were treated with IQ at various
      times thereafter and IQ-DNA binding levels were measured in the liver and colon 6
      h after carcinogen exposure. Compared with controls given IQ alone, CHL inhibited
      binding by 79% at 0 h and 40% at 1 h in the liver, and by 63% at 0 h, 38% at 1 h
      and 58% at 24 h in the colon (P < 0.05 by Student's t-test). These results
      support a mechanism involving complex formation between CHL and IQ in vivo and
      suggest that the inhibitor is likely to be most effective when ingested
      simultaneously with the carcinogen.

PMID- 8149494
TI  - Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts and increased p53 protein in
      mouse skin.
AB  - p53 protein expression has been shown to increase in response to DNA damage in
      cell culture systems. We have studied p53 expression and benzo[a]pyrene (B[a]P)
      induced DNA-damage in the form of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA
      adducts as measured by synchronous fluorescence spectrophotometry (SFS) in B[a]P
      treated C57BL/6 mouse skin. Polyclonal murine antibody CM5, which is comparable
      to human CM1, detecting both wild-type and mutated protein, was used. BPDE-DNA
      adducts reached their maximum at 24 h after all dosage regimens, but were very
      well detectable also at 12 and 48 h after the treatment, while no adducts were
      measurable at 1 week and thereafter. p53 expression was seen in 9/17 (53%) skin
      samples from mouse treated with 500 microgram of B[a]P 12-48 h after the
      treatment, while all 25 (100%) cases of similarly treated mouse skins were
      negative after 30 weeks of the treatment. Only one positive sample of total 11
      was found among mice treated with repeated 62.5 micrograms doses and this was 24
      h after the last treatment. After one 62.5 micrograms dose all mice were
      negative. This is the first report of an association of p53 protein with DNA
      damage in vivo and gives support for the putative function of p53 in cellular
      defense machinery towards chemical damage.

PMID- 8149495
TI  - Sequential analysis of K-ras mutations in aberrant crypt foci and colonic tumors
      induced by azoxymethane in Fischer-344 rats on high-risk diet.
AB  - Forty Fischer-344 male rats were given a high-risk diet (HRD) that was high in
      fat, low in fiber and low in calcium. After 4 weeks, the rats were given two
      weekly s.c. injections of azoxymethane (AOM, 15 mg/kg body wt), and remained on
      the same diet till death. Eight rats were killed at 12 weeks and again at 20
      weeks in order to microdissect aberrant crypt foci (ACF) containing four or more
      crypts/focus from their colons. The remaining 24 rats were killed at 30 weeks to
      harvest colonic tumors. The polymerase chain reaction (PCR) was used to amplify
      specific DNA segments in the K-ras gene from ACF and colonic tumors. The PCR
      amplified DNAs were sequenced to identify the point mutations in codons 12 and
      13. All the mutations detected in the ACF and colonic tumors were G to A
      transitions in the second position of codon 12. These mutations were present in
      the ACF of 2/8 (25%) and 3/8 (37%) rats at 12 and 20 weeks respectively. The
      mutations were present in colonic tumors of 7/24 (29%) rats. These results
      provide important evidence for the significance of K-ras mutations in ACF (> 4
      crypts/focus) as early markers of malignant potential in the colons of F344 rats
      exposed to AOM while receiving a high-risk western style diet.

PMID- 8149496
TI  - Five of six protein kinase C isoenzymes present in normal mucosa show reduced
      protein levels during tumor development in the human colon.
AB  - Protein kinase C (PKC) isoenzyme patterns were analyzed from human colonic
      epithelial cells of normal, premalignant and malignant origin. PKCs alpha, beta
      and zeta were found predominantly in the cytosol and the subtypes delta, epsilon
      and neta almost exclusively in the particulate fraction. Of the isoenzymes found
      beta, epsilon and neta were low in abundance and could only be detected after
      partial purification of cellular fractions on DE52-cellulose. Only PKC beta was
      similar in abundance in normal mucosa, premalignant and malignant colonic
      epithelial cells, while all other isoenzymes were decreased in abundance in tumor
      cells. The loss of PKC protein in tumor cells correlated with a loss in enzyme
      activity, as has been described before by other groups, especially affecting the
      Ca(2+)-dependent isoenzymes. On the other hand, activation of PKC by phorbol
      ester treatment in vivo was only possible in carcinoma cells (4/4) and a subset
      of adenomas (3/7). Normal human colonic epithelial cells did not respond to TPA
      treatment with either stimulation of PKC activity or translocation of cytosolic
      enzymes to the particulate fraction. Instead, TPA treatment resulted in a rapid
      loss of protein for the isoenzymes alpha, delta and to a lesser degree also beta.
      We assume that this reflects qualitative differences in response between normal
      and tumor cells, that may be due to the differences in isoenzyme distribution.

PMID- 8149497
TI  - Expression of cytokines, TNF-alpha and IL-1 alpha, in MAM acetate and 1
      hydroxyanthraquinone-induced colon carcinogenesis of rats.
AB  - The expression of cytokines, TNF-alpha and IL-1 alpha, was examined by means of a
      reverse transcription followed by PCR (RT-PCR) in rat colon carcinogenesis. Forty
      male F344 rats were used and divided into four groups. At the start of the
      experiment, 20 rats were treated with methylazoxymethanol (MAM) acetate (25 mg/kg
      body wt, one time, i.p.) and divided into two groups; group 1 was exposed to 1% 1
      hydroxyanthraquinone (1-HAQ) and group 2 was fed a basal diet during the
      experiment (40 weeks). Other rats were also divided into two groups; group 3 was
      exposed to 1% 1-HAQ as group 1, and group 4 was used as control. Tumor incidence
      (100%) and multiplicity (5.00 +/- 2.05) in group 1 were significantly greater
      than those in group 2 (20% and 0.2 +/- 0.42) and group 3 (10% and 0.10 +/- 0.32)
      (P < 0.01 and P < 0.01 respectively). RT-PCR technique with RNA was applied to
      the tissues from colon neoplasms and mucosa in each group. Expression of TNF
      alpha and IL-1 alpha in the colon neoplasms was much stronger than that in the
      colon mucosa of each group (P < 0.001 and P < 0.01 respectively). The expression
      of TNF-alpha was more remarkable in the colon mucosa of group 1 than that in
      corresponding tissue of groups 2 and 3 (P < 0.01). The expressions of TNF-alpha
      and IL-1 alpha were more increased in the colon mucosa of groups 1, 2 and 3 than
      that in group 4 as control (P < 0.01 and P < 0.05 respectively). The results
      indicate that TNF-alpha and IL-1 alpha may act as growth factors in rat colon
      carcinogenesis by MAM acetate and 1-HAQ. In addition, the synergistic effect of 1
      HAQ with MAM acetate in colon carcinogenesis might be related to biological
      effects of the cytokines expressed in the inflammatory condition generated by 1
      HAQ.

PMID- 8149498
TI  - Growth inhibition of rat liver epithelial tumor cells by monoterpenes does not
      involve Ras plasma membrane association.
AB  - The role of altered ras oncoprotein (Ras) farnesylation and membrane association
      in the growth inhibitory effects of several monoterpenes (limonene, perillic
      acid, perillyl alcohol, menthol, pinene and cineole) was investigated in rat
      liver epithelial cells. All of the above compounds except cineole inhibited the
      growth of viral Ha-ras-transformed rat liver epithelial cells (WB-ras cells) at
      concentrations of 0.25-2.5 mM. These cells, however, were not necessarily more
      sensitive to these compounds compared to non-transformed and viral raf
      transformed rat liver epithelial cells. Growth inhibition by limonene, perillic
      acid and pinene was only partially restored (20-50%) by supplementing the culture
      medium with 2 mM mevalonic acid. Western blot analyses of cytosolic and
      membranous fractions of WB-ras cells treated with monoterpenes indicated no
      change in Ras distribution. In contrast, lovastatin, a potent inhibitor of 3
      hydroxy-3-methyl-glutaryl coenzyme A reductase and Ras farnesylation,
      specifically reduced WB-ras cell growth and increased cytosolic levels of Ras.
      Thus, monoterpene-induced growth inhibition of rat liver epithelial cells was
      dissimilar to lovastatin and did not appear to involve altered Ras plasma
      membrane association.

PMID- 8149499
TI  - Children with epilepsy and their families: needs and services.
AB  - Social factors play a major role in determining the impact of epilepsy on
      families. This paper reviews the literature on the needs of families and their
      social networks, and services proposed for them. The predominantly negative
      picture presented in the 'expert' literature is compared with the more positive
      one presented in first-hand studies of families' views and in the literature on
      children with other disabilities. The implications of these differing
      perspectives for service provision are discussed.

PMID- 8149500
TI  - Conservation-withdrawal reaction in infancy? An underdescribed entity.
AB  - Conservation-withdrawal is considered a biological non-pathological process
      subserving survival in circumstances which pose an extreme threat to an infant,
      child or adult. Although initially described in an infant, is reported frequency
      in that age group seems sparse. Four infants are described, three of whom
      presented with weight loss. Despite their mothers' assertions that their breast
      feeding was adequate, the three infants gained weight rapidly on complementary
      feeding and became more responsive. Previously they had passively accepted sub
      optimal intakes, crying little and sleeping excessively. When their initial
      crying and objection went unheeded, they seemed to pass into a conservation
      withdrawal state, conserving their energies, biologically adapting to their
      mothers' inability to provide adequate nutrition. These infants did not appear
      ill and investigations proved normal. With adequate feeding, rapid improvement
      was observed in their weight gain, activity and responsiveness with normal
      development. Their mothers' selective denial of their own inadequate breast
      supply resulted in their inability to perceive their infants appropriately,
      depriving them of their nutritional needs. Additional factors of emotional
      deprivation and neglect may have occurred in the fourth infant. The responses of
      these infants observed during their period of severe stress, may appropriately be
      characterised by Engel's conservation-withdrawal state.

PMID- 8149501
TI  - Clumsiness in children: a defect of kinaesthetic perception?
AB  - Abnormal clumsiness in otherwise normal children has been recognized for many
      years, but the causes of this disorder are heterogeneous or unknown. Although
      equivocal, there is some evidence from reaction time studies suggesting that
      clumsiness is associated with a defect in perception of movement in the
      kinaesthetic modality and of motor programming. In this experiment clumsy
      children and matched controls performed simple and choice kinaesthetic reaction
      time tasks with either simple or complex responses. The requirement to
      discriminate between kinaesthetic stimuli was found to increase reaction time
      more for clumsy than for control children, but increasing response complexity had
      no significant effect on the reaction time of either group. These results were
      interpreted as suggesting that clumsiness is associated with a perceptual defect
      in the kinaesthetic modality, but providing no support for an association of
      clumsiness with a defect of motor programming.

PMID- 8149502
TI  - Implications of a model of stress and coping for services to families of young
      disabled children.
AB  - Much recent research on families bringing up a disabled child has explored their
      coping strategies to deal with stress. The major findings are reviewed, and
      possible implications for the structure and content of service delivery
      suggested. The paper emphasizes the importance of social support networks,
      including the relationship between the mother and father, and of quality services
      in enhancing parental adaptation.

PMID- 8149503
TI  - The comparative efficacy of antecedent exercise and methylphenidate: a single
      case randomized trial.
AB  - This study evaluated the comparative efficacy of antecedent exercise,
      methylphenidate (Ritalin), and placebo in the reduction of hyperactive behaviour
      in a pre-school boy. A single-case alternating treatments experimental design was
      employed for a total of 82 days. The dependent variable was the Conners'
      Abbreviated Symptom Questionnaire. Antecedent exercise failed to reduce
      hyperactive behaviour. Methylphenidate produced significantly less hyperactive
      behaviour than both placebo and antecedent exercise (P = 0.0238). Neither
      methylphenidate nor antecedent exercise produced notable side-effects as measured
      by the Monitoring of Side-Effects Scale. These data add to a sparse literature on
      the effects of antecedent exercise and methylphenidate amongst pre-school
      children.

PMID- 8149504
TI  - Bacterial translocation following abdominal trauma in humans.
AB  - Bacterial translocation in humans has been identified only with small bowel
      obstruction and in trauma patients. Our aim was to determine whether the
      occurrence of bacterial translocation correlates with clinical outcome in trauma
      patients. All patients requiring exploratory celiotomy for abdominal trauma over
      a 2-month period were considered for the study. Gross fecal contamination of the
      abdomen was the only exclusion criterion. Five patients with small bowel injuries
      without obvious contamination were included. Patients received preoperative
      antibiotics. Once surgical hemostasis and injury repair were complete, two
      mesenteric lymph nodes were harvested--one for quantitative culture, the other
      for electron microscopic evaluation. Postoperatively, patients were monitored for
      infection via temperature, white blood cell (WBC) count, and, when indicated,
      chest X-ray (CXR) and culture. Statistical analysis utilized ANOVA (P < 0.05
      significant) and linear regression. Sixteen patients were included in the study.
      Fifteen patients sustained penetrating abdominal trauma, one blunt. Six patients
      presented in Class I hemorrhagic shock, four in Class II, and two in Class III.
      The remaining four were not in hemorrhagic shock. Thirteen patients demonstrated
      bacterial translocation: one by culture alone, nine by electron microscopy, and
      three by both culture and electron microscopy. Statistical analysis of these
      three groups and patients without evidence of infection failed to reveal
      significant difference in average age, injury severity, hospital days, or
      incidence of postoperative infection. Bacterial translocation occurs following
      abdominal trauma in humans. Electron microscopic evaluation of mesenteric lymph
      nodes demonstrated that the incidence of translocation is greater than
      anticipated by culture alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149505
TI  - Platelet activating factor impairs pressor responses to noradrenaline in the
      anaesthetized rat but does not mediate endotoxin-induced hyporeactivity.
AB  - A nonhypotensive dose of endotoxin (Escherichia coli lipopolysaccharide, 250
      micrograms kg-1 h-1) impaired both the pressor responsiveness to noradrenaline
      and its effects in reducing renal and hindquarter blood flow, measured using
      ultrasound Doppler flow probes. Platelet activating factor (PAF, 50 ng kg-1 h-1)
      similarly impaired pressor responsiveness to noradrenaline, although this effect
      was accompanied by marked hypotension. These actions of PAF were prevented by
      pretreatment with the PAF antagonists WEB 2086 (20 mg kg-1) or BN 50739 (10 mg kg
      1) 15 min before commencing the infusion. However, neither antagonist modified
      the effect of endotoxin in impairing vascular responsiveness to noradrenaline.
      Thus, these results do not support a role for PAF in mediating endotoxin-induced
      vascular hyporeactivity, at least in the early stages of endotoxaemia.

PMID- 8149506
TI  - Early hemodynamic and renal effects of tumor necrosis factor alpha: role of
      thromboxane.
AB  - TNF alpha is an early mediator of endotoxemic shock. Its acute effect on renal
      hemodynamics is not known. In this study, the early hemodynamic and renal effects
      of TNF alpha were investigated in a rabbit model of shock, in which the
      measurement of the aortic blood flow before the bifurcation of the renal arteries
      allows one to differentiate between prerenal factors and hemodynamic renal
      response. Six groups of rabbits were studied, receiving either: (1) endotoxin,
      (2) endotoxin + thromboxane inhibitor Dazmegrel, (3) TNF alpha, (4) TNF alpha +
      Dazmegrel, (5) TNF alpha+indomethacin, or (6) placebo. Between 60 min and 3 hr
      after the injection, endotoxin induced a mean fall in arterial pressure of 32% (P
      < 0.01) and TNF alpha of 16% (P < 0.01). After endotoxin, the aortic blood flow
      decreased by 27% (P < 0.01) and after TNF alpha by 18% (P < 0.001). Both specific
      thromboxane inhibition and indomethacin abolished the TNF alpha central
      hemodynamic effect. The renal blood flow (-53%), the renal fraction of the aortic
      blood flow (-38%), and the glomerular filtration rate (-47%, P < 0.05) decreased
      1 hr after endotoxin injection. In contrast, TNF alpha induced only a slight fall
      of the renal fraction of the aortic blood flow (-19%) after 2.5 hr. Glomerular
      filtration was not modified after TNF alpha injection most likely because of a
      17% mean increase of filtration fraction in this group (P < 0.001). These data
      indicate that TNF alpha is implicated in the early hemodynamic changes of
      endotoxemic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149507
TI  - Effects of hypertonic saline solutions in the coronary circulation.
AB  - The use of small-volume injections of hypertonic saline solutions (HSS) in
      resuscitation from hemorrhagic shock is accompanied by well-maintained and
      pronounced increases in coronary blood flow (CBF) and by increases in myocardial
      contractility. The present study was performed in open-chest, anesthetized dogs
      to evaluate the contribution of direct coronary vasodilator and positive
      inotropic effects of HSS to these therapeutic responses. The left anterior
      descending coronary artery (LAD) was cannulated and perfused at constant pressure
      (100 mm Hg) with normal arterial blood. CBF in LAD was measured
      electromagnetically, and used to calculate myocardial oxygen consumption (MVO2)
      and coronary arterial plasma osmolality. Percent segmental shortening in LAD bed
      (% SS) was evaluated with ultrasonic crystals. Measurements were obtained during
      infusion into LAD of 2.5, 5.0, and 7.5% HSS at 2 ml/min. These HSS solutions
      yielded calculated plasma osmolalities of 329 +/- 3, 361 +/- 8, and 378 +/- 10
      mOsm/kg, respectively. The increases in plasma osmolality by 2.5% HSS were in the
      therapeutic range, whereas those by 5.0 and 7.5% HSS were supertherapeutic. HSS
      caused initial peak increases in CBF (reflecting decreases in coronary vascular
      resistance), which waned rapidly to achieve modest steady-state increases within
      2-3 min. The magnitude of the peak and steady-state increases in CBF by HSS
      correlated to osmolality. The 2.5% HSS had no effect on MVO2 and % SS, whereas
      the 5.0% and 7.5% HSS increased these variables in an osmolality-dependent
      manner. CONCLUSIONS: (1) intracoronary infusions of HSS caused modest steady
      state coronary vasodilation, (2) Supertherapeutic elevations of plasma osmolality
      by HSS were required for direct positive inotropic effects, and (3) the present
      findings suggest that the direct cardiac actions of HSS contribute minimally to
      the increases in coronary blood flow and myocardial contractility that follow the
      use of these solutions for resuscitation from hemorrhagic shock.

PMID- 8149508
TI  - Role of xanthine oxidase inhibition in survival from hemorrhagic shock.
AB  - The irreversible loss of adenine nucleotides and the formation of free radicals
      have both been suggested as causes of irreversibility following prolonged
      hemorrhagic shock. This study was performed to assess the effect of xanthine
      oxidase inhibition (allopurinol 50 mg/kg/day), free radical scavenging
      (superoxide dismutase 15,000 u/kg, catalase 15,000 u/kg, dimethylsulfoxide 20
      mg/kg, and alpha tocopherol 100 mg/kg/day) or both, on the 24-hr survival of dogs
      subjected to irreversible haemorrhagic shock. Twenty anesthetized dogs were bled
      to a mean arterial pressure of 30 mm Hg for 4 hr. The dogs were allocated to a
      control, an allopurinol pretreated, a free radical scavenger, or a combined
      treatment group. Both groups pretreated with allopurinol had significantly
      improved survival (P < 0.05) over that seen in the control group, but the free
      radical scavenger treated group was not significantly different from the control
      group. This study demonstrates the beneficial effect of xanthine oxidase
      inhibition on survival, and suggests that it may be due to preservation of
      adenine nucleotides rather than prevention of free radical formation.

PMID- 8149509
TI  - Pulmonary vascular effects of endotoxin in canine lobes pretreated with dapsone.
AB  - Endotoxin results in a granulocyte mediated loss of hypoxic pulmonary
      vasoconstriction (HPV). Dapsone blocks the granulocyte respiratory burst and
      might, therefore, preserve HPV following endotoxin. Isolated-perfused canine
      lobes (n = 6) were pretreated with 18 mg/kg dapsone (dapsone group), and compared
      to six lobes which did not receive dapsone (control group). Total pulmonary
      vascular resistance (Rtot) and arterial, middle (Rm), and venous segmental
      resistances were calculated by a vascular occlusion technique. We then
      administered endotoxin (2 mg/kg) and repeated measurements at 5, 30, and 90 min.
      The increase in Rm during 3% O2 compared to 35% O2 ventilation was used to define
      the presence of HPV. In the control group, following endotoxin, values of Rm did
      not change (P > 0.05) during 3% O2 ventilation (0.011 +/- 0.006 cm H2O/ml/min)
      compared with 35% O2 ventilation (0.014 +/- 0.005 cm H2O/ml/min). In the dapsone
      group, following endotoxin, values of Rm increased (P < 0.05) during 3% O2
      ventilation (0.06 +/- 0.026 cm H2O/ml/min) compared with 35% O2 ventilation (0.03
      +/- 0.015 cm H2O/ml/min). Changes in 6-keto PGF1 alpha or thromboxane B2 do not
      explain these observations. We conclude that in this experimental preparation,
      pretreatment with dapsone prevents the loss of HPV associated with endotoxin.

PMID- 8149510
TI  - Changes in tissue antioxidant enzyme activities and lipid peroxides in endotoxin
      induced multiple organ failure.
AB  - Intravenous administration of bacterial endotoxin (lipopolysaccharide: LPS)
      induces shock and disseminated intravascular coagulation in rats. Our report here
      shows that LPS-administered rats (10 mg/100 g) develop tissue injuries and
      functional disorders in multiple vital organs. In the present study, we
      investigated changes in tissue antioxidant enzyme activities, neutrophil
      sequestration, and lipid peroxides in multiple organs (lung, stomach, small
      intestine for antioxidant enzyme activities and neutrophil sequestration; lung,
      stomach, small intestine, liver, abdominal aorta for lipid peroxides) of LPS
      treated rats. LPS-treated animals morphologically revealed pulmonary interstitial
      edema, alveolar hemorrhage, and mucosal hemorrhage in the small intestine 45 min
      after LPS administration. Blood samples withdrawn from LPS-treated animals
      exhibited increases in serum amylase, blood urea nitrogen, creatinine, and
      transaminase levels up to 180 min post-LPS infusion. LPS-treated animals showed a
      significant increase in tissue myeloperoxidase (MPO) activities of the lung, but
      not of the small intestine and stomach 45 min after LPS infusion. Thiobarbituric
      acid reactive substances (TBARS) in the lung, small intestine, stomach, liver,
      and abdominal aorta significantly increased at 45 min post-LPS-infusion. Tissue
      superoxide dismutase (SOD) activities of the LPS-treated animals demonstrated a
      significant decrease in the lung, which suffered from severe insults and
      neutrophil sequestration; no significant change in the small intestine, which
      suffered from morphological insults without neutrophil sequestration, and a
      significant increase in the stomach, which showed no histological impairment, at
      180 min post-LPS administration. Glutathione peroxidase (GSH-PX) activities of
      the lung and small intestine showed no significant change in LPS-treated rats,
      while those of the stomach revealed a marked increase.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8149511
TI  - Lung and systemic oxidant and antioxidant activity after graded smoke exposure in
      the rat.
AB  - We wanted to determine the effect of a graded smoke inhalation on lung and
      systemic oxidant stress, and its relationship to physiological and histological
      change. Male Wistar rats were given 12 breaths of 10 ml/kg (n = 8) (group 1) or
      20 ml/kg (n = 8) (group 2) tidal volume, using cotton toweling smoke through the
      trachea using positive pressure. Rats were monitored, then killed at 24 hr. Data
      were compared to controls (n = 8). Peak group 1 and group 2 carboxyhemoglobins
      were 22 +/- 6 and 46 +/- 6%, with a mortality prior to 24 hr of 14% and 50%,
      respectively. Group 1 rats showed only moderate lung dysfunction but with severe
      airway inflammation and edema, alveolar inflammation and atelectasis, with a
      decrease in PaO2 from the control of 96 +/- 4 to 72 +/- 5 torr. No increase in
      lung, liver, or kidney oxidant-induced lipid peroxidation, measured as
      malondialdehyde lung, liver, or kidney oxidant-induced lipid peroxidation,
      measured as malondialdehyde (MDA), or decrease in the antioxidant defenses
      catalase was noted. Group 2 rats demonstrated severe airways edema, alveolar
      atelectasis, and alveolar edema, and a PaO2 decreasing below 60 torr,
      corresponding with a 3-fold increase in lung tissue MDA and 35% decrease in
      catalase. In addition, liver and kidney tissue MDA doubled, and catalase activity
      decreased by 40%. Increased oxygen consumption was also demonstrated.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8149512
TI  - Peter Debyeprize 1994 on Molecular Biology of Cardiovascular Diseases-
      Fundamental and Clinical Aspects Awarded to Drs Lydie Rappaport, Ketty Schwartz,
      and Bernard Swynghedauw from Unit 127 of INSERM, Paris, France. Committee of
      Deans, University of Limburg.

PMID- 8149513
TI  - Prevention and translation activities. Delivering the goods.

PMID- 8149514
TI  - Constituents key to Congressional passage of increased federal funding for
      biomedical research.

PMID- 8149515
TI  - Variable expression of the estrogen receptor in normal and atherosclerotic
      coronary arteries of premenopausal women.
AB  - BACKGROUND: The relative absence of coronary atherosclerosis in premenopausal
      women has been established. Estrogen is presumed to play a role in the protection
      of coronary arteries from atherosclerosis, and part of this protective effect
      appears to be mediated by amelioration of serum lipid profiles. However, all of
      the atheroprotective effect of estrogen is not explained by alteration of serum
      lipids. In this study, we attempt to identify evidence of estrogen receptors in
      coronary artery specimens of female patients and in human vascular smooth muscle
      cells. METHODS AND RESULTS: Postmortem coronary artery specimens were obtained
      from premenopausal (n = 18) and postmenopausal (n = 22) women who died with
      significant coronary artery disease (n = 19) and from noncardiac causes with
      normal coronary arteries (n = 21). Sections were examined for evidence of
      estrogen receptor expression using a monoclonal antibody stain. Radioligand
      binding assays for estrogen receptors were performed on human vascular smooth
      muscle cells in culture, and gel retardation assays were performed to confirm the
      presence of functional estrogen receptors. Estrogen receptor expression was
      identified by immunostaining in a total of 21 coronary arteries, with the
      majority of normal arteries (15 positive of 21 total, P = .0117) demonstrating
      evidence of estrogen receptor expression. Conversely, a minority (6 of 19, P =
      NS) of atherosclerotic arteries were positive for estrogen receptor expression.
      Furthermore, the relation between estrogen receptor expression and absence of
      coronary atherosclerosis was most evident in premenopausal subjects, with 10 of
      12 normal arteries in this group demonstrating evidence of estrogen receptors,
      whereas only 1 of 6 atherosclerotic coronary arteries was positive (P = .0062).
      Radioligand binding assays confirmed the presence of estrogen receptors at
      significant concentrations in intact human vascular smooth muscle cells. Gel
      retardation assays also documented the presence of functional estrogen receptors
      in extracts from human vascular smooth muscle cells. CONCLUSIONS: This
      investigation provides evidence of estrogen receptors in smooth muscle cells from
      human coronary arteries. The demonstrated relation between the presence of the
      receptors and the absence of atherosclerosis in premenopausal women suggests that
      these receptors may play a functional role in coronary atheroprotection.

PMID- 8149516
TI  - A new approach for local intravascular drug delivery. Iontophoretic balloon.
AB  - BACKGROUND: Catheter-based systems are being developed to deliver drugs directly
      into the vessel wall. Pressure-mediated trauma and lack of homogeneous delivery
      are key limitations of these approaches. METHODS AND RESULTS: We studied a new
      catheter-based delivery system that uses electrical current to force the drug
      into the vessel wall. The in vivo feasibility of this approach has been assessed
      by delivering 125I-hirudin into porcine carotid arteries. Vascular levels of
      hirudin after active iontophoresis (4 mA/cm2, 5 minutes) were 80-fold greater
      than those achieved by passive diffusion (without electricity). Tissue hirudin
      levels declined over time; by 1 hour after delivery, 80% of the drug had left the
      vessel wall, and by 3 hours later, the levels of hirudin within the wall were
      similar to those achieved by passive diffusion. Autoradiography revealed
      distribution of the drug throughout the entire circumference of the arterial wall
      within the intima, media, and adventitia. Iontophoresis-mediated vessel wall
      trauma was minimal (less than 10% endothelial denudation and medial smooth muscle
      cell damage). Balloon injury after local delivery changed neither kinetics nor
      distribution of the drug into the arterial wall. CONCLUSIONS: (1) High local
      concentrations of hirudin in the arterial wall may be achieved with the
      iontophoretic balloon catheter. (2) The drug is distributed throughout the entire
      vessel wall without significant damage. (3) The retention of hirudin in the
      arterial wall is time dependent. (4) This technique might be useful to deliver
      therapeutic agents before or after percutaneous vascular interventions.

PMID- 8149517
TI  - Heparin neutralization by platelet-rich thrombi. Role of platelet factor 4.
AB  - BACKGROUND: Platelets contain several factors that inhibit heparin. This study
      was designed to assess the heparin-neutralizing activity present in acute,
      platelet-rich arterial thrombi formed at sites of arterial injury in animals.
      METHODS AND RESULTS: Platelet-rich thrombi (n = 3) were induced in pig coronary
      arteries by balloon catheter-mediated arterial injury. Soluble extracts were
      prepared from each thrombus and assayed for the capacity to inhibit heparin in an
      in vitro clotting assay (activated partial thromboplastin time). Mean heparin
      neutralizing activity was 28 U of heparin neutralized per milliliter of thrombus,
      indicating that 1 vol of coronary thrombus completely inhibited the heparin
      present in 140 vols of therapeutically anticoagulated (0.2 U heparin/mL) plasma.
      In contrast, thrombus extracts had no effect on the anticoagulant activity of
      hirudin, a direct-acting thrombin inhibitor. The heparin-neutralizing activity
      present in coronary thrombi bound to heparin-agarose and was eluted from it by
      1.4 mol/L NaCl, suggesting that platelet factor 4 mediated the antiheparin effect
      of thrombi. Consistent with this hypothesis, a murine monoclonal antibody to
      rabbit platelet factor 4 nearly completely inhibited the heparin-neutralizing
      activity present in rabbit thrombi (n = 3) generated by carotid artery injury.
      CONCLUSIONS: Extracts prepared from platelet-rich arterial thrombi significantly
      inhibit the in vitro anticoagulant potency of heparin but not of hirudin. This
      antiheparin effect appears to be mediated by platelet factor 4. These results are
      consistent with the hypothesis that localized inhibition of heparin at sites of
      platelet activation may reduce its antithrombotic efficacy. In addition, they
      suggest an additional mechanism for the apparent superiority of hirudin over
      heparin as a thrombin inhibitor at sites of arterial injury.

PMID- 8149518
TI  - Short-term cholesterol lowering decreases size and severity of perfusion
      abnormalities by positron emission tomography after dipyridamole in patients with
      coronary artery disease. A potential noninvasive marker of healing coronary
      endothelium.
AB  - BACKGROUND: Cholesterol lowering over 1- to 3-year trials is associated with
      modest regression or no progression of focal coronary artery stenoses compared
      with progression in controls, a decrease in cardiac events proportionately more
      than the modest improvement in percent stenosis, and in experimental animals
      improved endothelial-mediated coronary vasodilation. METHODS AND RESULTS:
      Accordingly, we hypothesized that there would be improvement in size and severity
      of perfusion abnormalities by rest-dipyridamole positron emission tomography
      (PET) imaging in a randomized intensive cholesterol-lowering trial with each
      patient studied after a baseline control period, a 90-day intensive cholesterol
      lowering treatment, and a final control period off cholesterol-lowering regimens.
      Completely automated, objective measures of size and severity of perfusion
      abnormalities on rest-dipyridamole PET images were made by computer algorithm in
      12 patients with coronary artery disease. There were statistically significant
      decreases (improvement) in size and severity of perfusion abnormalities by rest
      dipyridamole PET on comparison of baseline control with perfusion abnormalities
      after intensive 90-day cholesterol lowering and significant increases (worsening)
      in size and severity after the final control period, respectively, as follows.
      (1) The percent of left ventricle outside 2.5 SD of normal values on the
      dipyridamole-to-rest ratio image of normalized counts was 22 +/- 20% after the
      initial control period, 13 +/- 14% after the treatment period, and 26 +/- 22%
      after the final control period with a significant decrease (improvement)
      occurring between the initial control and treatment periods (P = .02) and an
      increase (worsening) occurring between the treatment and final control periods (P
      = .009). (2) The percent of left ventricle with a ratio of < or = 0.66 in the
      dipyridamole-to-rest ratio image of normalized counts was 11 +/- 13% after the
      initial control period, 5.8 +/- 10% after the treatment period, and 14 +/- 19%
      after the final control period with a significant decrease (improvement)
      occurring between the initial control and treatment periods (P = .04) and an
      increase (worsening) occurring between the treatment and final control periods (P
      = .02). (3) The myocardial quadrant on the polar display with the lowest average
      activity expressed as a percent of maximal activity was 0.81 +/- 0.18 after the
      initial control period, 0.87 +/- 0.014 after the treatment period, and 0.77 +/-
      0.23 after the final control period with significant improvement occurring
      between the initial control and treatment periods (P = .05) and worsening
      occurring between the treatment and final control periods (P = .05). CONCLUSIONS:
      These results suggest that relatively short-term, intensive cholesterol lowering
      over 90 days improves myocardial perfusion capacity before anatomic regression of
      stenoses occurs and that such improvement, or deterioration after withdrawal of
      lipid-lowering treatment, can be followed noninvasively by dipyridamole PET,
      reflecting the integrated flow capacity of the entire coronary
      arterial/arteriolar vascular system affected by diffuse atherosclerosis.

PMID- 8149519
TI  - The Australian Schools Health and Fitness Survey. Physical fitness related to
      blood pressure but not lipoproteins.
AB  - BACKGROUND: Recent research indicates that levels of conventional coronary heart
      disease risk factors in children are related to the premature development of
      atheroma. It is therefore important to determine how risk factors might be
      modified on a population scale in children. METHODS AND RESULTS: In 1985, the
      Australian Schools Health and Fitness Survey was conducted on a representative
      sample of Australian schoolchildren aged 7 to 15 years. In children aged 9, 12,
      and 15, data on plasma cholesterol, triglycerides, and high-density lipoprotein
      cholesterol were obtained along with measurements of blood pressure, fitness, and
      body fatness. From an original sample of 2400 in these three age categories 1919
      underwent the full set of measurements. Univariate analysis of these data
      revealed a strong association between body fatness and plasma lipids. There was
      no significant association between fitness (measured as physical work capacity at
      a heart rate of 170 beats per minute per kilogram of lean body mass) and plasma
      lipids, but a significant negative association was found for fitness and systolic
      blood pressure (r = -.12, P < .001). Multiple regression analysis revealed that
      the association of fitness with systolic blood pressure was only partly accounted
      for by the confounding effect of lower body fatness in fitter children.
      CONCLUSIONS: These data collected on a representative sample of children under
      standardized conditions confirm a previous finding of a link between fitness and
      blood pressure in schoolchildren and also support a growing consensus that
      fitness is only weakly linked to plasma lipids and lipoproteins in children and
      adolescents.

PMID- 8149520
TI  - Effects of tissue plasminogen activator and a comparison of early invasive and
      conservative strategies in unstable angina and non-Q-wave myocardial infarction.
      Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia.
AB  - BACKGROUND: Although coronary thrombosis plays a critical role in the
      pathogenesis of unstable angina and non-Q-wave myocardial infarction (NQMI), the
      effects of thrombolytic therapy in these disorders is not clear. Also, the role
      of routine early coronary arteriography followed by revascularization has not
      been established. METHODS AND RESULTS: Patients (n = 1473) seen within 24 hours
      of ischemic chest discomfort at rest, considered to represent unstable angina or
      NQMI, were randomized using a 2 x 2 factorial design to compare (1) TPA versus
      placebo as initial therapy and (2) an early invasive strategy (early coronary
      arteriography followed by revascularization when the anatomy was suitable) versus
      an early conservative strategy (coronary arteriography followed by
      revascularization if initial medical therapy failed). All patients were treated
      with bed rest, anti-ischemic medications, aspirin, and heparin. The primary end
      point for the TPA-placebo comparison (death, myocardial infarction, or failure of
      initial therapy at 6 weeks) occurred in 54.2% of the TPA-treated patients and
      55.5% of the placebo-treated patients (P = NS). Fatal and nonfatal myocardial
      infarction after randomization (reinfarction in NQMI patients) occurred more
      frequently in TPA-treated patients (7.4%) than in placebo-treated patients (4.9%,
      P = .04, Kaplan-Meier estimate). Four intracranial hemorrhages occurred in the
      TPA-treated group versus none in the placebo-treated group (P = .06). The end
      point for the comparison of the two strategies (death, myocardial infarction, or
      an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in
      18.1% of patients assigned to the early conservative strategy and 16.2% of
      patients assigned to the early invasive strategy (P = NS). In the latter, the
      average length of initial hospitalization, incidence of rehospitalization within
      6 weeks, and days of rehospitalization all were significantly lower. CONCLUSIONS:
      In the overall trial, patients with unstable angina and NQMI were managed with
      low rates of mortality (2.4%) and myocardial infarction or reinfarction (6.3%) at
      the time of the 6-week visit. These results can be achieved using either an early
      conservative or early invasive strategy, the latter resulting in a reduced
      incidence of days of hospitalization and of rehospitalization and in the use of
      antianginal drugs. The addition of a thrombolytic agent is not beneficial and may
      be harmful.

PMID- 8149521
TI  - Recombinant hirudin for unstable angina pectoris. A multicenter, randomized
      angiographic trial.
AB  - BACKGROUND: Coronary artery thrombosis plays an important pathophysiological role
      in unstable angina and non-Q-wave myocardial infarction. To date, heparin and
      thrombolytic therapy has not provided complete or consistent benefit. We
      hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent
      accumulation of coronary artery thrombus in a manner superior to heparin. METHODS
      AND RESULTS: Patients with rest ischemic pain, abnormal ECG, and baseline
      angiogram indicating a > or = 60% stenosis of a culprit coronary artery or
      saphenous vein graft with visual appearance of thrombus were randomized to one of
      two different doses of heparin (either a target activated partial thromboplastin
      time [aPTT] of 65 to 90 or 90 to 110 seconds) or one of four doses of hirudin
      (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 infusion) in a dose-escalating protocol.
      After 72 to 120 hours of study drug, a repeat coronary angiogram was obtained,
      and the paired studies underwent quantitative analysis. The primary end point was
      change in the average cross-sectional area of the culprit lesion. Other efficacy
      end points also involved changes in culprit lesion dimensions and TIMI flow
      grade. Recombinant hirudin led to a dose-dependent elevation of aPTT that
      appeared to plateau at the 0.2-mg/kg dose. A higher proportion of hirudin-treated
      patients had their aPTT within a 40-second range (16% heparin versus 71% hirudin,
      P < .001). Overall, the 116 patients treated with hirudin tended to show more
      improvement than the 50 patients receiving heparin relative to the primary
      efficacy variable--the average cross-sectional area (P = .08)--as well as minimal
      cross-sectional area (P = .028), minimal luminal diameter (P = .029), and percent
      diameter stenosis (P = .07). CONCLUSIONS: Recombinant hirudin appears to be a
      promising antithrombotic intervention compared with heparin for inhibition of
      coronary artery thrombus. Large-scale comparative trials are warranted.

PMID- 8149522
TI  - A pilot, early angiographic patency study using a direct thrombin inhibitor as
      adjunctive therapy to streptokinase in acute myocardial infarction.
AB  - BACKGROUND: The success of streptokinase in acute myocardial infarction is
      hampered by the high failure rate to achieve early reperfusion. This study
      evaluates the possible benefit of Hirulog (Biogen, Cambridge, Mass), a direct
      thrombin inhibitor, as adjunct therapy to streptokinase to enhance early patency
      and prevent rethrombosis. Heparin has been shown to be of very limited benefits
      in this setting. METHODS AND RESULTS: Forty-five patients were randomized to
      Hirulog or heparin (2:1 ratio). Coronary angiography documented a TIMI 2 or 3
      flow after 90 minutes in 77% of the patients treated with Hirulog and
      streptokinase and in 47% of patients treated with heparin and streptokinase (P <
      .05) and after 120 minutes in 87% and 47% of patients, respectively (P < .01).
      TIMI 3 flow was established in 77% of patients with Hirulog compared with 40%
      with heparin (P < .02). The clinical outcome and the bleeding rate was also
      favorable to Hirulog; no reocclusion was observed at late angiography performed
      4.7 days later. CONCLUSIONS: Hirulog in this pilot study significantly improved
      the early patency rate of the infarct-related artery with a favorable clinical
      profile. This new direct thrombin inhibitor exhibits promise as adjunctive
      therapy to thrombolysis.

PMID- 8149523
TI  - Plasma endothelin determination as a prognostic indicator of 1-year mortality
      after acute myocardial infarction.
AB  - BACKGROUND: Plasma endothelin concentrations are increased in the acute phase of
      myocardial infarction and in chronic heart failure. Since endothelin may
      contribute to hemodynamic deterioration by potent vasoconstrictory and
      cardiotoxic actions, increased plasma levels may be associated with an
      unfavorable prognosis after myocardial infarction. METHODS AND RESULTS: We tested
      the hypothesis that plasma endothelin determination in the subacute phase of
      myocardial infarction is related to subsequent survival and assessed whether
      plasma endothelin measurements provide additional prognostic information to that
      obtained from clinical and biochemical variables previously known to be
      associated with high mortality. Plasma endothelin determination was obtained from
      142 patients (average age +/- SD, 67.8 +/- 10.1 years) on day 3 after documented
      myocardial infarction and was related to 1-year mortality. Sixteen patients died
      during the follow-up period. In a univariate Cox proportional-hazards model, day
      3 plasma endothelin concentrations were significantly related to mortality (P <
      .0001). Patient age, previous treatment for systemic hypertension, presence of
      clinical heart failure, and plasma atrial natriuretic factor levels were all
      related to mortality in univariate analysis but provided no additional prognostic
      information to that obtained from endothelin determination in a multivariate
      model. CONCLUSIONS: Plasma endothelin concentrations are strongly related to
      outcome after myocardial infarction and provide prognostic information
      independent of clinical and biochemical variables previously associated with a
      poor prognosis.

PMID- 8149524
TI  - Endothelin in human congestive heart failure.
AB  - BACKGROUND: Although recent investigations report the elevation of plasma
      endothelin (ET) in congestive heart failure (CHF), it remains unclear if this
      elevation is that of the biologically active peptide ET-1 or of its precursor big
      ET. Furthermore, it is unclear if such elevation is associated with increased
      myocardial ET and if the molecular form from cardiac tissue is altered ET. Last,
      it remains to be established whether circulating ET is increased at the earliest
      stage of CHF in patients with asymptomatic left ventricular dysfunction and
      correlates with the magnitude of ventricular dysfunction. METHODS AND RESULTS:
      The present study was designed to investigate concentrations and molecular forms
      of ET in plasma and cardiac tissue in healthy subjects and CHF patients with New
      York Heart Association (NYHA) class I through IV using cardiac radionuclide
      angiogram, cardiac myocardial biopsy, radioimmunoassay, gel permeation
      chromatography (GPC), and immunohistochemical staining (IHCS). Plasma ET was
      increased only in patients with moderate (NYHA class III) or severe (NYHA class
      IV) CHF compared with healthy subjects and individuals with asymptomatic (NYHA
      class I) or mild (NYHA class II) CHF. The elevation of circulating ET in CHF
      showed a negative correlation with left ventricular ejection fraction and cardiac
      index and a positive correlation with functional class and left ventricular end
      diastolic volume index. GPC demonstrated that immunoreactive plasma ET was ET-1
      in healthy subjects and both mature ET-1 and its precursor big-ET in severe CHF
      patients, with big-ET the predominant molecular form. Cardiac tissue
      concentrations and IHCS revealed ET presence in healthy atrial and ventricular
      tissue, which were not different in severe CHF. GPC revealed that the molecular
      form of cardiac ET was ET-1 in both healthy and CHF hearts. CONCLUSIONS: The
      present study establishes for the first time that the elevation of plasma ET in
      severe human CHF represents principally elevation of big-ET. Second, ET is
      present in healthy and failing myocardia, and its activity by both
      immunohistochemistry and radioimmunoassay is not changed in CHF. Furthermore, the
      elevated plasma ET is characteristic of severe CHF and not asymptomatic or mild
      CHF. In addition, the degree of plasma elevation of ET correlates with the
      magnitude of alterations in cardiac hemodynamics and functional class. The
      present study confirms and extends previous investigations of ET in human CHF and
      establishes the evolution of circulating and local cardiac ET in the spectrum of
      human CHF.

PMID- 8149525
TI  - Use of therapeutic ultrasound in percutaneous coronary angioplasty. Experimental
      in vitro studies and initial clinical experience.
AB  - BACKGROUND: Previous studies have shown the feasibility of peripheral arterial
      ultrasound angioplasty. METHODS AND RESULTS: In this report, we describe the use
      of percutaneous therapeutic ultrasound for coronary angioplasty. In vitro, 11
      postmortem, atherosclerotically occluded coronary arteries were obtained to
      assess catheter-delivered ultrasound for arterial recanalization as well as for
      assessment of the size of particulate debris. Clinically, coronary ultrasound
      angioplasty was performed in 19 patients (mean age, 56 years) to assess safety
      and feasibility for the treatment of obstructive coronary atherosclerosis. Three
      patients with unstable angina and 16 with exercise-induced myocardial ischemia
      were treated with a prototype 4.6F coronary catheter ultrasound ablation device
      with a 1.7-mm diameter ball tip. The ultrasound coronary catheter delivered
      ultrasound energy at 19.5 kHz, with a power output of 16 to 20 W at the
      transducer. Energy is delivered in a pulsed mode with a 50% duty cycle of 30
      milliseconds. Patients were treated for a mean of 493 seconds (range, 130 to 890)
      with intracoronary ultrasound ablation. All lesions were treated with adjunctive
      balloon angioplasty. All 11 postmortem coronary occlusions were recanalized, and
      99% of the particulates generated were < 10 microns in diameter. We found that
      after ultrasound, mean (+/- SD) coronary arterial stenosis fell from 80 +/- 12%
      to 60 +/- 18% (P < .001) and to 26 +/- 11% (P < .001) after adjunctive balloon
      angioplasty. Mean pressures required to achieve full balloon inflation were 2.7
      atm (range, 1 to 5.5) with a median of 3.0-mm balloon size (2.5 to 3.5). No
      ultrasound-related complications were identified. CONCLUSIONS: Intracoronary
      ultrasound plaque ablation appears to be safe. Our findings suggest that catheter
      delivered high-intensity, low-frequency ultrasound may be useful for lesion
      debulking and enhancing arterial distensibility, allowing balloon dilation at
      relatively low pressures.

PMID- 8149526
TI  - Lipoprotein(a) in restenosis after percutaneous transluminal coronary angioplasty
      and coronary artery disease.
AB  - BACKGROUND: The purpose of the study was to investigate the relation of
      lipoprotein(a) and serum lipid parameters to restenosis after percutaneous
      transluminal coronary angioplasty (PTCA) and to assess the association of these
      same biochemical markers to coronary artery disease (CAD) in individuals with
      angiographically defined normal and diseased coronary arteries. METHODS AND
      RESULTS: Sixty-two patients with successful PTCA had follow-up angiography at 35
      +/- 10 weeks. Restenosis occurred in 21 male patients (46%) and 6 female patients
      (38%). Elevated apolipoprotein B (P < .01) and decreased high-density lipoprotein
      2 cholesterol (P < .02) were found to be independently associated with restenosis
      after angioplasty, whereas lipoprotein(a) was not. Eighty-five patients
      undergoing PTCA were compared with 46 subjects who had no evidence of CAD on
      angiography. Elevated lipoprotein(a) (P < .001) and reduced apolipoprotein A1 to
      B ratio (P < .001) were found to be strong independent risk factors for the
      presence of CAD when adjustment was made for age (P < .005), male sex (P < .01),
      smoking (P < .005), and hypertension (P = .06). CONCLUSIONS: Serum lipoprotein(a)
      levels are not associated with restenosis after PTCA, but elevated levels are
      strongly associated with CAD. Low-serum, high-density lipoprotein-2 cholesterol
      concentration and elevated apolipoprotein B concentration were found to be
      associated with restenosis after PTCA.

PMID- 8149527
TI  - Tissue plasminogen activator, plasminogen activator inhibitor-1, and fibrin as
      indexes of clinical course in cardiac allograft recipients. An immunocytochemical
      study.
AB  - BACKGROUND: Tissue-type plasminogen activator (TPA) is the principal activator of
      plasminogen. Since hemostasis in the microcirculation of allografts is a well
      recognized complication of transplantation, we asked (1) whether the distribution
      and amount of cellular TPA in biopsies of transplanted human hearts are
      associated with fibrin deposits in and around the microcirculation, (2) whether
      such changes involve the physiological inhibitors of TPA and plasmin, and (3)
      whether the presence of these activators and inhibitors of fibrinolysis in tissue
      is correlated with clinical outcome. METHODS AND RESULTS: We immunocytochemically
      quantified the presence of fibrin, plasmin, TPA, and the TPA inhibitor PAI-1 in
      938 biopsies from 68 consecutive cardiac allografts over a 54-month period. The
      localization, distribution, and quantification of TPA in arteriolar smooth muscle
      cells revealed that 35 of the 68 allografts maintained vascular TPA reactivity
      consistent with time-zero biopsies of autologous donor hearts: this was
      designated as the normal TPA group. In contrast, 33 of the 68 allografts
      significantly lost vascular TPA reactivity compared with time-zero biopsies of
      autologous donor hearts: this was designated as the depleted TPA group. Analysis
      of sequential biopsies from both groups during 54 months revealed that the mean
      cumulative quantitative TPA value for the normal TPA group was 1.0 +/- 0.01,
      whereas the depleted TPA group value was 1.9 +/- 0.02 (P = .0001), and the mean
      cumulative quantitative fibrin value for the normal TPA group was 1.0 +/- 0.01,
      whereas the depleted TPA group value was 1.5 +/- 0.05 (P = .0001). Biopsies of
      allografts in the depleted TPA group contained endothelial reactivity for TPA-PAI
      1 complexes, whereas biopsies from the normal TPA group did not. Plasmin
      associated molecules were rarely identified in biopsies of the normal TPA group
      but were present in the depleted TPA group, and the fibrin-to-plasmin ratio in
      the normal TPA group always was less than the fibrin-to-plasmin ratio in biopsies
      from the depleted TPA group. Analysis of demographic and risk factors revealed no
      significant differences between patients in the normal and depleted TPA groups,
      but none of the 35 patients in the normal TPA group died or were retransplanted,
      and 13 of the 33 patients in the depleted TPA group died or required
      retransplantation (P = .0001). CONCLUSIONS: Time-zero hearts (n = 68) and 34 of
      38 stable allografts contained immunocytochemically detectable TPA only in
      vascular smooth muscle cells. Twenty-nine of 30 patients with normal TPA in their
      time-zero biopsies who subsequently developed a poor clinical outcome were found
      to have depleted TPA in biopsies evaluated during their first postoperative month
      and remained depleted throughout the study. Of 33 patients with depleted TPA, 39%
      died or required retransplantation. Depleted arteriolar TPA associated
      significantly with vascular and interstitial deposits of fibrin, plasmin, and
      endothelial TPA-PAI-1 complexes. These findings indicate that hemostatic and
      fibrinolytic pathways are activated in falling allografts, and they reveal
      evidence of depleted TPA before clinical or histopathological signs of failure.
      Patients with such allografts were found to be at high risk of death
      independently of other widely used clinical/laboratory parameters of prediction.

PMID- 8149528
TI  - Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in
      patients with congestive heart failure.
AB  - BACKGROUND: Since organic nitroesters and endothelium-derived nitric oxide
      mediate vasodilation through a final common pathway, that is, by activation of
      soluble guanylate cyclase in vascular smooth muscle, nitroglycerin (NTG) could
      specifically enhance the endothelium-dependent vasodilatory response to
      acetylcholine (Ach) in patients with congestive heart failure (CHF) and
      endothelial cell dysfunction. Accordingly, the net effects of an intra-arterial
      infusion of NTG (10(-9) mol/L) on endothelium-dependent and endothelium
      independent vasodilation were assessed in the forearm circulation of patients
      with CHF. METHODS AND RESULTS: The forearm blood flow responses to intra-arterial
      administration of graded concentrations of Ach (10(-7) to 10(-5) mol/L) were
      determined by venous occlusion plethysmography (mL/min per 100 mL) in 18 patients
      with CHF and 5 age-matched normal subjects before and during intra-arterial
      infusion of NTG (10(-9) mol/L) for 20 minutes. In eight patients, the duration of
      the infusion of NTG (n = 5) or vehicle control solution (n = 3) was extended to
      12 hours with measurement of the forearm blood flow responses to Ach at 20
      minutes, 4 hours, and 12 hours. In five additional patients, forearm blood flow
      response to intra-arterial administration of two doses of phentolamine (0.05 and
      0.5 mg) were determined before and during a 20-minute NTG infusion. Regional
      administration of NTG 10(-9) mol/L did not change resting forearm blood flow in
      either normal subjects or patients with CHF. Before administration of NTG 10(-9)
      mol/L, intra-arterial infusions of Ach 10(-7), 10(-5) and 10(-5) mol/L increased
      forearm blood flow to 14.7 +/- 6.2, 20.2 +/- 4.7, and 38.4 +/- 7.9 mL/min per 100
      mL in normal subjects and to 4.1 +/- 0.8, 5.0 +/- 1.1, and 10.6 +/- 2.3 mL/min
      per 100 mL in patients with CHF. After administration of NTG 10(-9) mol/L for 20
      minutes, the vasodilatory response to Ach significantly increased to 5.6 +/- 1.0,
      6.9 +/- 1.6, and 17.7 +/- 3.4 mL/min per 100 mL in patients with CHF but did not
      change in normal subjects. The enhanced forearm blood flow responses to
      administration of Ach observed after 20 minutes of NTG administration in patients
      with CHF were sustained throughout a 12-hour NTG infusion. In contrast, regional
      administration of NTG did not change the vasodilatory responses to phentolamine.
      CONCLUSIONS: NTG, when administered intra-arterially for 20 minutes at a dose
      that does not affect resting forearm blood flow, specifically increased the
      vasodilatory response to intra-arterial administration of Ach in patients with
      CHF but not in normal subjects. The vasodilatory response to Ach was consistently
      enhanced by low-dose NTG throughout a 12-hour period. The vasodilating effects of
      organic nitroesters on the peripheral vasculature of patients with CHF may result
      in part from an interaction with the vascular endothelium.

PMID- 8149529
TI  - Effect of L-arginine on coronary endothelial function in cardiac transplant
      recipients. Relation to vessel wall morphology.
AB  - BACKGROUND: Coronary endothelial vasodilator dysfunction is a common finding in
      cardiac transplant recipients and may represent an early marker for the
      development of intimal thickening and graft atherosclerosis. The present study
      tested the hypothesis that endothelial dysfunction precedes intimal thickening
      and that administration of L-arginine, the precursor of endothelium-derived
      relaxing factor, improves endothelial vasodilator function of coronary conduit
      and resistance vessels if given at an early stage of graft atherosclerosis.
      METHODS AND RESULTS: Acetylcholine (10(-6), 10(-5), 10(-4) mol/L) was infused
      into the left anterior descending or circumflex artery and repeated after
      intravenous infusion of L-arginine (10 mg.kg-1.min-1 over 20 minutes) in 18
      cardiac transplant recipients. Epicardial responses were evaluated by
      quantitative angiography, and the microcirculation was studied by determination
      of coronary blood flow with a Doppler flow velocity wire. Intimal thickening was
      assessed by intravascular ultrasound (n = 14). In epicardial coronary arteries,
      acetylcholine tended to elicit vasoconstriction. Epicardial coronary
      vasoconstriction elicited by acetylcholine was attenuated by infusion of L
      arginine (10(-4) mol/L, -6.8% versus -2.8%; P < .01); this beneficial effect was
      observed predominantly in patients with normal intravascular ultrasound
      characteristics. In coronary resistance vessels, acetylcholine induced
      vasodilation, reflected by increases in coronary blood flow. The acetylcholine
      induced increase in blood flow was significantly enhanced with L-arginine (at a
      dose of 10(-4) mol/L, + 121% versus 176%; before versus after L-arginine, P <
      .002). CONCLUSIONS: The coronary vasculature of cardiac transplant recipients
      exhibits a generalized endothelial dysfunction of conduit and resistance vessels.
      L-Arginine improves endothelial dysfunction of both coronary microvasculature and
      epicardial coronary arteries. The reversibility of epicardial endothelial
      dysfunction by L-arginine is more likely in vessels with normal wall morphology.

PMID- 8149530
TI  - Effects of cardiac transplantation on bioenergetic abnormalities of skeletal
      muscle in congestive heart failure.
AB  - BACKGROUND: Patients with advanced heart failure have bioenergetic abnormalities
      of skeletal muscle metabolism during exercise. Using 31P magnetic resonance
      spectroscopy, we sought to determine whether skeletal metabolic responses to
      exercise are normalized by orthotopic cardiac transplantation. METHODS AND
      RESULTS: Four groups were studied: healthy normal volunteers (n = 9), subjects
      awaiting heart transplantation (n = 10), subjects < 6 months (mean, 4 months)
      after transplant (n = 9), and subjects > 6 months (mean, 15 months) after
      transplant (n = 8). None of the posttransplant patients had biopsy evidence of
      rejection at the time of study. There were no significant differences in age,
      preoperative functional class, or symptom duration among the three patient
      groups. Metabolic responses were monitored in the dominant arm during incremental
      weight pull exercise and 10 minutes of recovery by 31P magnetic resonance
      spectroscopy, with measurement of pH and the phosphocreatine (PCr)/(PCr +
      inorganic phosphate [Pi]) ratio, an index of PCr concentration. In addition,
      based on recovery data, the rate of PCr resynthesis was calculated as a measure
      of oxidative metabolism that is independent of work level, recruitment, or muscle
      mass, and the effective maximal rate of mitochondrial ATP synthesis (Vmax) was
      determined. Analysis was by ANOVA. There were no differences between groups in pH
      or PCr/(PCr + Pi) at rest. Compared with the normal control group, the
      pretransplant group had a decreased exercise duration (11.3 +/- 2.5 versus 15.0
      +/- 1.3 minutes, P = .02), a lower submaximal exercise PCr/(PCr + Pi) ratio (0.58
      +/- 0.11 versus 0.76 +/- 0.08, P < .05), a reduced PCr resynthesis rate (13 +/- 6
      versus 22 +/- 9 mmol/L per minute, P < .05), and a lower calculated Vmax (26 +/-
      14 versus 53 +/- 26 mmol/L per minute, P < .05). In the group studied early after
      transplantation, all the changes noted in the pretransplant group persisted and
      were if anything somewhat worse. In the group studied late after transplantation,
      there was a significant improvement in the PCr resynthesis rate compared with the
      early-posttransplant group (27 +/- 6 late versus 15 +/- 6 mmol/L per minute
      early, P < .05) and statistically nonsignificant trends toward improvements in
      submaximal exercise pH (6.86 +/- 0.24 late versus 6.72 +/- 0.24 early) and
      submaximal PCr/(PCr + Pi) ratio (0.56 +/- 0.14 late versus 0.44 +/- 0.15 early)
      and Vmax (45 +/- 21 late versus 33 +/- 15 mmol/L per minute early). However,
      compared with normal subjects, exercise duration and submaximal PCr/(PCr + Pi)
      were still reduced in the late-posttransplant group. CONCLUSIONS: Despite
      successful heart transplantation, skeletal muscle abnormalities of advanced heart
      failure persist for indefinite periods, although partial improvement occurred at
      late times. The persistent abnormalities may contribute to the reduced exercise
      capacity that is present in most patients after transplantation.

PMID- 8149531
TI  - Cardiovascular responses during static exercise. Studies in patients with
      complete heart block and dual chamber pacemakers.
AB  - BACKGROUND: During static exercise in normal subjects, the mean arterial pressure
      increases as a result of an increase in heart rate and thereby cardiac output
      with no significant change in stroke volume or systemic vascular resistance. We
      hypothesized that if one component of the blood pressure response to static
      exercise, ie, heart rate, were fixed, plasticity of the neural control mechanisms
      during exercise would allow for preservation of the blood pressure response by
      alternative mechanisms. METHODS AND RESULTS: Thirteen patients 20 to 68 years old
      with structurally normal hearts, complete heart block, and dual chamber
      pacemakers performed static exercise during three conditions: (1) normal dual
      chamber sensing and pacing mode, (2) heart rate fixed at the resting value
      obtained in the DDD mode of 78 +/- 4 beats per minute, and (3) heart rate fixed
      at the peak value obtained during exercise in the DDD mode of 94 +/- 4 beats per
      minute. Heart rate, blood pressure, and cardiac output were measured and stroke
      volume and systemic vascular resistance were calculated at rest and at 1 and 5
      minutes during static one-leg extension at 20% of maximal voluntary contraction.
      The mean arterial pressures at rest and at 5 minutes were higher when the heart
      rate was fixed at the faster peak exercise heart rate. In the DDD mode, heart
      rate increased by 16 beats per minute and cardiac output by 1.1 L/min, with a
      resultant 25 mm Hg increase in mean arterial pressure at 5 minutes with no change
      in the stroke volume or systemic vascular resistance. In both fixed heart rate
      pacing modes, mean arterial pressure increased by 24 mm Hg when the heart rate
      was fixed at the resting heart rate and by 25 mm Hg when the heart rate was fixed
      at the faster peak exercise heart rate pacing modes associated with an increase
      in stroke volume, with similar increases in cardiac output. During static
      exercise there was no change in systemic vascular resistance from the resting
      value in any pacing mode. CONCLUSIONS: When heart rate is fixed in the presence
      of normal left ventricular function, the mean arterial pressure increases
      normally during static exercise because of an increase in stroke volume with no
      change in the systemic vascular resistance.

PMID- 8149532
TI  - Cardiovascular responses to exercise. Effects of aging and exercise training in
      healthy men.
AB  - BACKGROUND: Cardiac aging alters many of the acute responses to exercise stress,
      but the extent to which chronic exercise (ie, training) can alter or improve the
      effects of aging in humans is largely unknown. METHODS AND RESULTS:
      Cardiovascular responses to graded supine exercise stress (beginning at 200 kpm
      and increasing by 200 kpm every 3 minutes till exhaustion) were assessed using
      radionuclide ventriculography in 13 older (age, 60 to 82 years) and 11 young
      (age, 24 to 32 years) rigorously screened healthy men before and after 6 months
      of endurance training. Repeated-measures ANOVA was used to test significance.
      During exercise, the old group had a lesser increase in heart rate (+105% old
      versus +166% young), a greater increase in mean blood pressure (+35% old versus
      +22% young), lesser increases in ejection fraction (+3 ejection fraction units
      old versus +11 units young) and peak ejection rate (+62% old versus +119% young),
      a greater increase in end-diastolic volume index (+8% old versus -10% young), a
      lesser fall in end-systolic volume index (-0% old versus -32% young), and a
      lesser increase in cardiac index (+135% old versus +189% young) (all P < .01
      young/old versus exercise stage). Stroke volume index response to exercise was
      not different with aging (+14% old versus +6% young, P = NS). Exercise training
      increased maximal oxygen intake by 21% in the older group (28.9 +/- 4.6 to 35.1
      +/- 3.8 mL.kg-1.min-1, P < .001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/
      6.3 mL.kg-1.min-1, P < .001) and increased peak workload by 24% in the old and
      28% in the young. Exercise training had no differential effects on old versus
      young men. Among all subjects, training significantly reduced the resting heart
      rate by 12% (-8 beats per minute) and increased resting end-diastolic volume
      index by 13% (+9 mL/M2) and resting stroke volume index by 18% (+7 mL/M2) (all P
      < .01). At peak exercise, cardiac index increased by 16% (+1.07 L.M-2.min-1)
      compared with before training, which was the result of an increase in stroke
      volume of 18% (+7 mL/M2) (P < .001); peak heart rate was unchanged. The increase
      in stroke volume index at peak exercise was the result of both a 12% increase in
      end-diastolic volume index (+8 mL/M2) (P < .01) and an increase in ejection
      fraction (+3 ejection fraction units) (P < .05) at peak exercise. The increased
      ejection fraction at peak exercise occurred despite a 9% increase in systolic
      blood pressure (+18 mm Hg) (P < .01), suggesting an increase in contractility.
      Thus, both the young and old increased peak exercise cardiac output by use of the
      Frank-Starling mechanism (ie, cardiac dilatation) as well as an increase in
      ejection fraction. CONCLUSIONS: We conclude that there is an age-associated
      decline in heart rate, ejection fraction, and cardiac output responses to supine
      exercise in healthy men. Although the stroke volume responses of the young and
      old are similar, the old tend to augment stroke volume during exercise more
      through cardiac dilatation, with an increase in end-diastolic volume (+8%) but
      without much change in ejection fraction (+3 ejection fraction units), whereas
      the young rely more on an increase in the ejection fraction (+11 ejection
      fraction units) with no cardiac dilatation (-10%). Despite the significant
      cardiovascular changes that occur in the response to a single bout of exercise
      with aging, adaptations to chronic exercise training were not different with
      aging and included improvements in maximal workload and increases in ejection
      fraction, stroke volume index, and cardiac index at peak exercise.

PMID- 8149533
TI  - Assessment of effects of autonomic stimulation and blockade on the signal
      averaged electrocardiogram.
AB  - BACKGROUND: Signal-averaged ECG is a noninvasive test designed to detect "late
      potentials." The effects of alterations in autonomic tone on the signal-averaged
      ECG have not been evaluated systematically. METHODS AND RESULTS: The effects of
      autonomic stimulation and blockade on the signal-averaged ECG were evaluated in
      14 healthy subjects (8 men and 6 women; age, 28.5 +/- 4.8 years) on 2 separate
      days. The signal-averaged ECG was recorded at baseline and after physiological
      and pharmacologic beta-adrenergic stimulation (tilt, exercise, and epinephrine
      and isoproterenol infusions), sequential and combined beta-adrenergic and
      parasympathetic blockade, and alpha-adrenergic stimulation before and after
      parasympathetic blockade. Analysis was performed with a bidirectional filter (40
      Hz high-pass). Significant changes in the signal-averaged QRS duration from
      baseline (105.1 +/- 12.0 milliseconds) were noted with tilt (96.8 +/- 8.8
      milliseconds), tilt after double blockade (97.5 +/- 9.0 milliseconds),
      epinephrine (110.5 +/- 11.8 milliseconds), and isoproterenol (99.6 +/- 12.6
      milliseconds). Changes in the root-mean-square voltage of the terminal 40
      milliseconds and the low-amplitude (< 40 microV) signal duration paralleled the
      changes in the QRS duration. CONCLUSIONS: The signal-averaged ECG does not
      measure only "fixed" parameters but rather is altered under a variety of
      physiological and pharmacologic conditions. Upright tilt leads to shortening of
      the QRS duration before and after autonomic blockade; thus, the decrease in QRS
      duration with tilt may be related to factors other than changes in autonomic
      tone. These findings have implications for interpretation of the results of
      signal-averaged ECG.

PMID- 8149534
TI  - High-density mapping of electrically induced atrial fibrillation in humans.
AB  - BACKGROUND: Mapping studies in animals have suggested that atrial fibrillation
      (AF) is based on multiple reentering wavelets. Little information is available
      about the patterns of activation during AF in humans. The objective of the
      present study was to reconstruct and classify the patterns of human right atrial
      (RA) activation during electrically induced AF. METHODS AND RESULTS: AF was
      induced by rapid atrial pacing in 25 patients with Wolff-Parkinson-White syndrome
      undergoing surgery for interruption of their accessory pathway(s). The free wall
      of the RA was mapped using a spoon-shaped electrode containing 244 unipolar
      electrodes. The activation of the RA during AF showed large interindividual
      differences. Based on the complexity of atrial activation, three types of AF were
      defined. In type I (40% of patients), single broad wave fronts propagated
      uniformly across the RA. Type II (32%) was characterized by one or two
      nonuniformly conducting wavelets, whereas in type III (28%), activation of the RA
      was highly fragmented and showed three or more different wavelets that frequently
      changed their direction of propagation as a result of numerous arcs of functional
      conduction block. There were significant differences (P < .05) among the three
      types of AF in median intervals (174 +/- 28, 150 +/- 14, and 136 +/- 16
      milliseconds), variation in AF intervals (P5-95) (54 +/- 25, 94 +/- 21, and 104
      +/- 22 milliseconds), incidence of electrical inactivity (42 +/- 11%, 21 +/- 4%,
      and 8 +/- 4%) and reentry (3 +/- 7%, 36 +/- 28%, and 99 +/- 36%), and average
      conduction velocity during AF (61 +/- 6, 54 +/- 4, and 38 +/- 10 cm/s).
      CONCLUSIONS: During pacing-induced AF in humans, the RA is activated by one or
      multiple wavelets propagating in different directions. Three types of RA
      activation during AF were identified. From type I to type III, the frequency and
      irregularity of AF increased, and the incidence of continuous electrical activity
      and reentry became higher. These various types of AF in humans appear to be
      characterized by different numbers and dimensions of the intra-atrial reentrant
      circuits.

PMID- 8149535
TI  - Radiofrequency ablation therapy in idiopathic left ventricular tachycardia with
      no obvious structural heart disease.
AB  - BACKGROUND: The feasibility and efficacy of radiofrequency ablation therapy in
      idiopathic left ventricular tachycardia has not been assessed in a large group of
      patients. METHODS AND RESULTS: Twenty consecutive patients with idiopathic left
      ventricular tachycardia and without structural heart disease underwent
      electrophysiological study, pharmacological interventions with administration of
      verapamil and adenosine, and radiofrequency ablation therapy. There were 17 men
      and 3 women with a mean age of 28 +/- 8 years. The QRS configuration during
      tachycardia was of right bundle branch block and superior axis in 13 patients,
      indeterminate axis in 6 patients, and right axis in 1 patient. The tachycardia
      was electrically inducible and responsive to verapamil but not to adenosine.
      Thirteen patients demonstrated entrainment. Activation and pace-mapping studies
      disclosed that the tachycardia originated from the inferior apical septum in 15
      patients, the midseptum in 4 patients, and the anterior lateral wall of the left
      ventricle in 1 patient. Radiofrequency ablation was successful in 17 of the 20
      patients (85%). The successful ablation sites were characterized by an
      endocardial activation time 30 milliseconds earlier than the onset of QRS during
      tachycardia and by a pace-mapping QRS similar to or closely resembling the
      tachycardia. All patients displayed sharp spikes preceding the local ventricular
      electrogram at the ablation site. However, these sharp spikes also were noted in
      15 control patients and were not specific for this tachycardia; they persisted
      after ablation. There were no complications. A follow-up of 7 +/- 8 months in the
      17 successfully ablated patients showed no symptomatic tachyarrhythmias without
      medications. Six patients underwent repeat electrophysiological study, and no
      induction of tachycardia was revealed. CONCLUSIONS: Radiofrequency ablation
      therapy is effective and safe in patients with idiopathic left ventricular
      tachycardia. It should be considered as the primary therapeutic modality in these
      patients.

PMID- 8149536
TI  - Detection of myocardial ischemia by 31P magnetic resonance spectroscopy during
      handgrip exercise.
AB  - BACKGROUND: The metabolic changes of myocardial ischemia in patients with
      coronary artery disease assessed by 31P magnetic resonance spectroscopy (MRS)
      have been reported previously. A significant decrease in the ratio of
      phosphocreatine (PCr) to ATP during handgrip exercise in a group of patients with
      severe coronary artery disease has been demonstrated. However, there are no
      reports at present that directly compare cardiac 31P MRS data with exercise 201Tl
      myocardial scintigraphy, now established as one of the most important clinical
      methods to assess myocardial ischemia. The purpose of this study was to
      investigate whether 31P MRS with handgrip exercise testing is able to detect
      myocardial ischemia, demonstrated by exercise 201Tl scintigraphy. METHODS AND
      RESULTS: Twenty-seven patients with severe stenosis of the left anterior
      descending coronary artery (> or = 75%) and 11 normal control subjects composed
      the present study. Patients were divided into two groups on the basis of exercise
      201Tl scintigraphy: a reversible 201Tl defect group (RD[+]) who demonstrated
      redistribution at the late image and a fixed 201Tl defect group (RD[-]). While
      lying supine within the magnet, subjects performed handgrip exercise at 30% of
      maximal force once in every two cardiac cycles. 31P MR spectra were collected
      before and during handgrip exercise. Data were corrected for the saturation
      factor. ANOVA revealed significant differences among the three groups with
      respect to the mean +/- SD PCr/ATP ratio at rest (control, 1.85 +/- 0.28 > RD(+),
      1.60 +/- 0.19 > RD(-), 1.24 +/- 0.30; P < .05). The PCr/ATP ratio decreased
      significantly from 1.60 +/- 0.19 at rest to 0.96 +/- 0.28 during exercise (P <
      .001) in the RD(+) group (n = 15). However, in the RD(-) group (n = 12), the
      ratio did not change significantly during handgrip exercise (1.24 +/- 0.30 at
      rest versus 1.19 +/- 0.28 during exercise). Similarly, the ratio did not change
      in the control group (n = 11) (1.85 +/- 0.28 at rest versus 1.90 +/- 0.23 during
      exercise). CONCLUSIONS: Contrary to normal subjects or patients with fixed
      thallium defects, the PCr/ATP ratio was significantly altered by exercise in
      patients with reversible thallium defects. These results suggest that 31P MRS
      with handgrip exercise testing is a sensitive method for detecting myocardial
      ischemia.

PMID- 8149537
TI  - Left ventricular mass and subsequent blood pressure changes among middle-aged men
      in rural and urban Japanese populations.
AB  - BACKGROUND: It has been suggested that echocardiographically determined left
      ventricular mass (LVM) is useful in the prediction of hypertension. To examine
      the relation between LVM and subsequent blood pressure (BP) change, a 6- to 8
      year follow-up was conducted in adult Japanese men. METHODS AND RESULTS: LVM was
      determined by M-mode echocardiography using the American Society of
      Echocardiography formula among 354 normotensive men aged 30 to 59 years from a
      rural community (n = 193) and from urban companies (n = 161) in Japan between
      1979 and 1983. BP was remeasured 6 to 8 years after baseline in 148 rural men
      (77%) and 127 urban men (79%). For men whose BP was remeasured, the mean +/- SD
      LVM index (LVM/body surface area [g/m2]) at baseline was 117 +/- 22 in rural men
      and 99 +/- 15 in urban men (the difference, P < .001). For both populations, LVM
      index was positively associated with age and physical activity but not with body
      mass index. Associations of LVM index with usual alcohol intake and initial BPs
      were generally weak. According to linear regression analyses after controlling
      for these covariates at baseline, a 20-g/m2 greater LVM index at baseline was
      associated with a 5 mm Hg increase in systolic and a 4 mm Hg increase in
      diastolic BP during the subsequent 6 to 8 years for urban men. A 1-mm greater
      average ventricular wall thickness was associated with a similar BP increase. For
      rural men, positive associations of LVM index with BP increase existed but were
      weak. The weaker association between LVM index and BP increase in rural compared
      with urban men was probably the result of effects of higher physical activity,
      leading to a larger left ventricular internal dimension. The increase in systolic
      and diastolic BPs over the 6 to 8 years of observation was significantly related
      to baseline LVM index in rural and urban men with a smaller internal dimension
      (rural men, < or = 49 mm; urban men, < or = 47 mm) but not in those with larger
      dimensions. CONCLUSIONS: An increased LVM index predicts subsequent BP increase
      in middle-aged normotensive men in the presence of a normal or small internal
      dimension.

PMID- 8149538
TI  - Comparison of intravascular ultrasound and angiography in the assessment of
      myocardial bridging.
AB  - BACKGROUND: In autopsy, myocardial bridging is a common finding. With coronary
      angiography, a systolic compression, mainly of the left anterior descending
      coronary artery, is observed in 1% to 3% of the patients. Controversy exists
      concerning the functional importance of this finding. To obtain a functional
      insight into the myocardial bridging, intravascular ultrasound and intracoronary
      Doppler were performed. METHODS AND RESULTS: Intracoronary ultrasound and Doppler
      were performed in 14 patients with angiographic evidence of systolic vessel
      compression ("milking effect") in the left anterior descending coronary artery.
      The 4.8F, 20-MHz ultrasound catheter could not be advanced through the entire
      myocardial bridge segment in 6 of the 14 patients studied because the lumen was <
      1.6 mm. In these patients, only the proximal parts of the bridge segment were
      scanned. The changes in cross-sectional shape during the cardiac cycle were
      determined for both the normal proximal segment and the bridge segment by use of
      a semiautomatic computer program. Intracoronary Doppler (20 MHz) was performed in
      7 patients with a 3F catheter. A highly characteristic systolic eccentric or
      concentric compression with delayed relaxation in diastole of the myocardial
      bridging segment was clearly visualized in all patients. The cross-sectional
      lumen area variation was 40 +/- 25% in the bridging segments and 9 +/- 7% in the
      normal segments (P < .01). No atherosclerotic lesions were detected in the bridge
      or the distal segment in the 8 patients in whom the IVUS catheter was
      successfully advanced through the entire myocardial bridge. However,
      atherosclerotic plaques were found in the segments proximal to the bridge in 12
      of 14 patients (86%). The resting mean flow velocity was 6.4 +/- 1.2 cm/s; the
      maximal mean flow velocity after intracoronary administration of 10 mg papaverine
      was 14.1 +/- 3.4 cm/s. The coronary flow velocity reserve was 2.2 +/- 0.7. A
      highly characteristic pattern showing a prominent peak in coronary velocity in
      early diastole was observed in 86% of patients, and this pattern was enhanced
      after injection of intracoronary papaverine. CONCLUSION: Intravascular ultrasound
      demonstrated a characteristic systolic compression of the bridge segments. The
      delayed compression release may explain the characteristic sharp early diastolic
      peak in coronary flow velocity found with intracoronary Doppler in vessels with
      myocardial bridging. Reduced coronary flow reserve may be related to this
      phenomenon, possibly explaining signs of ischemia detected in some of the
      patients, but may alternatively be a result of the presence of atherosclerosis in
      the segment proximal to the bridge in these patients.

PMID- 8149539
TI  - Survival in primary pulmonary hypertension. Validation of a prognostic equation.
AB  - BACKGROUND: The prognosis of patients with primary pulmonary hypertension (PPH)
      remains a major problem for the planning and assessment of therapeutic
      interventions. The objectives of this study were (1) to characterize mortality in
      a Mexican population of patients with PPH and to investigate factors associated
      with survival and (2) to test the applicability in this population of the
      prognostic equation proposed by the US National Institutes of Health study on
      PPH. METHODS AND RESULTS: A dynamic cohort of patients with PPH at our
      institution were enrolled between June 1977 and August 1991 and prospectively
      followed at regular intervals through September 1992. Measurements at diagnosis
      included hemodynamic and pulmonary function variables in addition to information
      on demographic data and medical history. The response to vasodilator treatment
      was also analyzed. The estimated median survival of the group was 4.04 years (95%
      confidence interval, 2.98 to 5.08 years). Variables associated with poor survival
      (univariate analysis) included an elevated mean right atrial pressure, a
      decreased cardiac index, and a decreased mixed venous PO2. A reduced forced vital
      capacity and the absence of vasodilator treatment were also associated with poor
      survival. A multivariate Cox proportional-hazards regression analysis was used to
      assess the adjusted hazard ratios, hence the relative contributions of the
      variables controlling for confounding. Reduced forced vital capacity and cardiac
      index and increased right atrial pressure were still significantly associated as
      risk factors for survival in patients with PPH. Survival as computed by the
      equation correlated with real survival of PPH patients with positive predictive
      values of 87%, 91%, and 89% at 1, 2, and 3 years, respectively. The equation,
      however, was relatively unable to predict deaths in our population, in part
      because of the strict limits of poor prognosis. CONCLUSIONS: Mortality in PPH is
      largely associated with hemodynamic variables that assess right ventricular
      function. The proposed prognostic equation had a high sensitivity and a
      relatively low specificity to predict survival in our PPH population. To improve
      this specificity it may be necessary to increase the limits of poor prognosis as
      defined by the equation.

PMID- 8149540
TI  - Arterial reactivity is significantly impaired in normotensive young adults after
      successful repair of aortic coarctation in childhood.
AB  - BACKGROUND: Despite successful repair of coarctation of the aorta in childhood,
      adult survivors often have hypertension at rest or on exercise, and their life
      expectancy is shorter than normal because of premature coronary and
      cerebrovascular disease. This may be related to persistent structural and
      functional arterial abnormalities after surgery. METHODS AND RESULTS: Using high
      resolution ultrasound, we studied the right brachial arteries of 25 normotensive
      young adults who had undergone successful repair of coarctation in childhood
      (mean age at repair, 62 months; range, 0 to 167 months, including 8 patients
      operated on in infancy; mean age at study, 19 years; range, 14 to 27 years) and
      50 age- and sex-matched control subjects. We assessed the degree of reactive
      hyperemia (RH) produced after distal cuff occlusion and release and the changes
      in arterial diameter in response to RH (with increased flow causing endothelium
      dependent dilation) and to glyceryltrinitrate (GTN, an endothelium-independent
      dilator). The response of the right femoral artery to GTN was also measured in 12
      coarctation subjects and 12 control subjects. Studies were performed 13.7 years
      (range, 7 to 21 years) after surgery. RH was significantly lower in coarctation
      subjects (343 +/- 130% versus 482 +/- 147%), as were endothelium-dependent
      dilation (3.8 +/- 3.3% versus 8.8 +/- 3.6%) and GTN response (13.3 +/- 6.0%
      versus 20.5 +/- 6.1%) (P < .001 for each), reflecting abnormal dilatory capacity
      in both the resistance and conduit arteries. In contrast, GTN-induced dilation in
      the femoral arteries was similar to that in control subjects (9.5 +/- 2.6% versus
      10.1 +/- 4.1%, P = .70). On multivariate analysis, GTN response and systolic
      blood pressure at peak exercise were inversely correlated (r = -.52, P = .04).
      Vascular responses were not related to the age at repair. CONCLUSIONS: Despite
      successful repair of coarctation in childhood, arterial dilation is significantly
      impaired in the precoarctation vascular bed of healthy young adults. This may be
      an important contributor to exercise-related hypertension and late morbidity or
      mortality.

PMID- 8149541
TI  - Independent predictors of long-term results after balloon pulmonary
      valvuloplasty. Valvuloplasty and Angioplasty of Congenital Anomalies (VACA)
      Registry Investigators.
AB  - BACKGROUND: This study was performed to determine independent predictors of long
      term outcome after percutaneous balloon dilation of congenital pulmonary valve
      stenosis. Smaller follow-up series of patients after balloon pulmonary
      valvuloplasty have shown inconsistent results regarding the independent relation
      between prognostic factors and long-term outcome, as many patient selection and
      technical factors are correlated. METHODS AND RESULTS: Follow-up data were
      obtained for 533 patients from 22 institutions at up to 8.7 years after an
      initial balloon pulmonary valvuloplasty. Patients were grouped based on defined
      long-term outcomes, and the independent effects of patient selection and
      technical factors were sought in multivariate statistical analyses. At follow-up,
      23% of patients were noted to have an outcome judged to be suboptimal because of
      either a residual right ventricle to pulmonary artery peak systolic gradient of >
      or = 36 mm Hg or further treatment of pulmonary stenosis requiring repeat balloon
      pulmonary valvuloplasty or surgical therapy. Significant independent predictors
      of a suboptimal long-term outcome included an earlier study year of the initial
      valvuloplasty (adjusted odds ratio, 0.71 per consecutive year), a small valve
      hinge point diameter (0.81 per 1-mm increase), and a higher immediate residual
      gradient (1.32 per 10 mm Hg increase). A smaller ratio of balloon to valve hinge
      point diameter significantly predicted suboptimal outcomes for patients with
      valve morphologies classified as typical (0.52 per 0.1 increase in ratio) and
      complex (primarily postsurgical valvotomy, 0.43) but not for patients with
      dysplastic (0.95) or combined morphologies (dysplasia with commissural fusion,
      1.01). Patient age, the presence of Noonan's syndrome or associated cardiac
      lesions, pre-balloon valvuloplasty hemodynamic parameters, and the use of a
      simultaneous double-balloon technique did not independently predict follow-up
      outcomes. CONCLUSIONS: Accurate prognostication after balloon pulmonary
      valvuloplasty depends on the careful determination of valvar anatomy. The use of
      an appropriate ratio of balloon to valve hinge point diameter in the setting of
      typical valve morphology will optimize the chance of long-term success.

PMID- 8149542
TI  - Effects of the KATP channel opener bimakalim on coronary blood flow, monophasic
      action potential duration, and infarct size in dogs.
AB  - BACKGROUND: The major purpose of the present study was to determine the effect of
      the potassium channel opener bimakalim, administered intracoronary only during
      the initial 10 minutes of ischemia, on myocardial infarct size in anesthetized
      dogs. A second aim was to test the possibility that bimakalim mediates its
      cardioprotective effects by accelerating the rate of myocyte action potential
      shortening during early ischemia. A third aim was to determine the relative
      potency of bimakalim to open coronary vascular ATP-regulated potassium (KATP)
      channels versus myocyte KATP channels. METHODS AND RESULTS: Barbital-anesthetized
      open-chest dogs were used. In the initial studies, bimakalim (0.1 to 10
      micrograms/min) was infused into the left anterior descending coronary artery
      (LAD), and changes in coronary blood flow and monophasic action potential
      duration (MAPD) were used as indexes of coronary vascular KATP channel and
      myocyte KATP channel activity, respectively. In subsequent infarct studies, dogs
      were subjected to 60 minutes of LAD occlusion followed by 4 hours of reperfusion.
      Based on preliminary studies, two doses of bimakalim that did not shorten MAPD
      during nonischemic conditions (0.1 and 0.3 microgram/min) and one that markedly
      shortened MAPD during nonischemic conditions (3.0 micrograms/min) or an equal
      volume of vehicle were infused into the LAD during the initial 10 minutes of
      coronary artery occlusion. Transmural myocardial blood flow was measured at 5 and
      30 minutes of occlusion by the radioactive microsphere technique, and infarct
      size was determined at the end of 4 hours of reperfusion by triphenyltetrazolium
      staining. The monophasic action potential duration at 50% repolarization (MAPD50)
      was measured by an epicardial probe placed in the center of the ischemic area.
      Bimakalim had an approximately 10-fold greater affinity for the coronary vascular
      than the myocardial KATP channel (ED50 coronary, approximately 0.3 microgram/min;
      ED50 myocyte, approximately 3.0 micrograms/min). Three doses of bimakalim (0.1,
      0.3, and 3.0 micrograms/min) all markedly reduced infarct size expressed as
      percent of the area at risk (12.6 +/- 3.3%, 14.5 +/- 2.2%, and 14.2 +/- 5.3%,
      respectively, versus 27.2 +/- 5.7% in controls) to nearly equal extents.
      Subsequently, we found that the two higher doses of bimakalim (0.3 and 3.0
      micrograms/min) markedly accelerated yet the 0.1-microgram/min dose of bimakalim
      did not significantly affect the ischemia-related shortening of the action
      potential during the initial 5 minutes of occlusion. In addition, 0.1 and 0.3
      microgram/min bimakalim did not increase the incidence of ventricular
      fibrillation during the 60 minutes of occlusion (0 of 7 and 0 of 8 dogs,
      respectively), whereas 3.0 micrograms/min bimakalim had a profibrillatory effect
      (6 of 6) compared with the control group (1 of 8). There were no significant
      differences between groups in systemic hemodynamics, myocardial oxygen demand,
      ischemic bed size, or collateral blood flow to the ischemic region. CONCLUSIONS:
      The results of the present study clearly reveal that a small dose (0.1 or 0.3
      microgram/min) of the KATP channel opener bimakalim administered only during the
      initial 10-minute period of ischemia markedly reduced myocardial infarct size to
      an extent equal to that of a higher profibrillatory dose in barbital-anesthetized
      dogs. These data also suggest that bimakalim and other potassium channel openers
      may partially exert their cardioprotective effects by accelerating KATP channel
      activation during early ischemia as evidenced by an enhanced rate of ischemic
      myocyte action potential shortening. However, the results also suggest that other
      cellular mechanisms may be involved in mediating the cardioprotection produced by
      a low dose of bimakalim (0.1 microgram/min) because it did not significantly
      accelerate the shortening of the action potential duration, yet it had an
      efficacy to redu BACKGROUND: The major purpose of the present study was to de

PMID- 8149543
TI  - Involvement of 5-HT2 receptors in chronic endothelial dysfunction after balloon
      injury of porcine coronary arteries.
AB  - BACKGROUND: Endothelium-dependent, pertussis toxin-sensitive relaxation to 5
      hydroxytryptamine (5-HT) is impaired selectively after balloon injury of porcine
      coronary artery, followed by regeneration of the endothelial cells. The present
      study was designed to test the hypothesis that 5-HT, released from aggregating
      platelets, affects the progression of the endothelial dysfunction. METHODS AND
      RESULTS: Yorkshire pigs were assigned randomly to three groups: control group
      (standard diet), denudation group (high-cholesterol diet plus balloon denudation
      of the endothelium of coronary artery under fluoroscopy), and DV-7028-treated
      group (denudation group plus chronic treatment with the selective 5-HT2 receptor
      antagonist DV-7028, given from the first day on after balloon denudation). Four
      weeks after the denudation, quantitative angiography revealed that 5-HT injected
      into the coronary artery decreased the luminal diameter of the left anterior
      descending coronary artery at the denuded site in the denudation group but not in
      the control or the DV-7028-treated group. Then, animals were killed so we could
      study the endothelium-dependent responses of their coronary arteries in
      conventional organ chambers. The arteries from the denudation group exhibited
      less relaxation to 5-HT and sodium fluoride (a stimulant of G proteins) than
      those of the control group. Relaxations to 5-HT and sodium fluoride were greater
      in arteries from the DV-7028-treated group than in those from the denudation
      group. In contrast, the endothelium-dependent, pertussis toxin-insensitive
      relaxations to bradykinin and thrombin and the endothelium-independent
      relaxations to sodium nitroprusside and isoproterenol were not affected
      significantly by chronic treatment with DV-7028. CONCLUSIONS: These results
      suggest that 5-HT2 receptors are involved in the chronic progression of
      endothelial dysfunction after balloon denudation in the porcine coronary artery.

PMID- 8149544
TI  - Liposome-bound prostaglandin E1 often prevents cyclic flow variations in stenosed
      and endothelium-injured canine coronary arteries.
AB  - BACKGROUND: Prostaglandin E1 is a potent vasodilator with anti-inflammatory and
      antiplatelet effects. We tested the hypothesis that prostaglandin E1 attenuates
      or prevents platelet aggregation-associated cyclic flow variations (CFVs) in
      severely stenosed and endothelium-injured coronary arteries. METHODS AND RESULTS:
      We induced CFVs in 21 dogs by placing an external constrictor around the left
      anterior descending coronary artery at the site where the endothelium had been
      mechanically injured. The blood flow velocity in the artery was monitored by a
      pulsed Doppler flow probe. Sixty minutes after CFVs were established, liposome
      bound prostaglandin E1, a stable formulation, was administered intravenously to
      12 dogs at incremental doses of 0.25, 0.5, 1, and 2 micrograms/kg body wt; it
      abolished CFVs in 8 of the 12 dogs (67%). After CFVs were eliminated, epinephrine
      was infused intravenously, and at a dose of 6.6 +/- 1.6 micrograms/min, it
      restored CFVs in 7 of 7 dogs. Control dogs (n = 9) were treated with free
      prostaglandin E1, which did not abolish CFVs in any dog. CONCLUSIONS: Liposome
      bound but not free prostaglandin E1 effectively diminishes CFVs in severely
      stenosed and endothelium-injured canine coronary arteries.

PMID- 8149545
TI  - Marked reduction in myocardial infarct size due to prolonged infusion of an
      antioxidant during reperfusion.
AB  - BACKGROUND: There has been controversy about whether early reperfusion of
      myocardial infarcts causes further necrosis mediated by reactive oxygen species
      or other mechanisms. Unequivocal evidence that therapeutic agents given only
      during reperfusion can prevent, rather than delay or modify, injury has been
      sparse. Failure to account for variables, such as collateral blood flow, that
      influence infarct size independently and attempts to measure infarct size too
      early in reperfusion may have limited the sensitivity and specificity of some
      previous studies. METHODS AND RESULTS: After 90 minutes of coronary occlusion and
      48 hours of reperfusion in a canine model, we examined the effect on infarct size
      of intravenous infusion of N-(2-mercaptopropionyl)-glycine (MPG), a diffusible
      antioxidant. Infarct size and region at risk were measured by post-mortem dual
      perfusion with triphenyl tetrazolium chloride and Evans blue dyes, and regional
      myocardial blood flow was measured with radioactive microspheres. Infusion of MPG
      100 mg.kg-1.h-1, beginning either 15 minutes before the onset of reperfusion or
      30 minutes after the onset of reperfusion and continued until 4 hours of
      reperfusion and followed by an intramuscular dose, reduced infarct size,
      normalized for both region at risk and the level of collateral blood flow, by 60%
      and 45%, respectively. When infusion of MPG was limited to the last 15 minutes of
      ischemia and the first hour of reperfusion only, the normalized infarct size was
      reduced by 26%. Heart rate, blood pressure, and their product did not differ
      among the four groups studied. The plasma half-time of MPG was < 10 minutes. In
      in vitro experiments MPG was a scavenger of hydrogen peroxide but not of
      superoxide radical. CONCLUSIONS: After 90 minutes of coronary ligation, infusion
      of the diffusible hydrogen peroxide scavenger, MPG, for several hours, beginning
      as late as 30 minutes after the onset of reperfusion, substantially reduced
      infarct size measured 48 hours later. In this model, necrosis caused by processes
      during reperfusion may be more extensive than necrosis caused by ischemia alone.
      Since infusion of this agent for only the first hour of reperfusion was
      considerably less effective, it appears that most of the oxidant injury leading
      to necrosis occurred after the first 60 minutes but within the first 4 hours of
      reperfusion.

PMID- 8149546
TI  - Combination of platelet fibrinogen receptor antagonist and direct thrombin
      inhibitor at low doses markedly improves thrombolysis.
AB  - BACKGROUND: We evaluated the effects of a novel platelet fibrinogen receptor
      antagonist, Integrelin, and a direct thrombin inhibitor, recombinant hirudin,
      given together with recombinant tissue plasminogen activator (rTPA) in a canine
      experimental model of intracoronary thrombosis. We tested the hypothesis that
      combination of both agents at low doses would have an additive antithrombotic
      effect, resulting in a significant improvement in the efficacy of rTPA. METHODS
      AND RESULTS: Thirty-two dogs with an electrically induced coronary thrombus were
      treated with rTPA (1 mg/kg over 20 minutes) together with one of the following
      adjunctive treatments in a random fashion. Eight dogs received saline for 90
      minutes; Integrelin (5 micrograms.kg-1.min-1 for 90 minutes) was given to 8 dogs;
      8 dogs received recombinant hirudin (20 micrograms.kg-1.min-1 for 90 minutes);
      and 8 dogs were treated with a low-dose combination of Integrelin (2.5
      micrograms.kg-1.min-1) plus recombinant hirudin (10 micrograms.kg-1.min-1) for 90
      minutes. Integrelin or recombinant hirudin, when given as single adjunct to rTPA,
      enhanced the lysis of the occlusive thrombus, causing full restoration of
      coronary blood flow (100% of its baseline value) for 29 +/- 16 and 26 +/- 5
      minutes, respectively, whereas coronary blood flow was fully restored for only 5
      +/- 1 minutes in dogs receiving rTPA plus saline (both P < .05). However, either
      Integrelin or recombinant hirudin failed to modify the reocclusion rate (57% and
      63%, respectively) compared with saline (83%; all P = NS). Conversely, the low
      dose combination therapy led to complete restoration of coronary blood flow for
      92 +/- 19 minutes (P < .01 versus all treatments) and significantly reduced the
      reocclusion rate (25%; P < .05 versus saline). CONCLUSIONS: These data show that
      inhibition of specific pathways of platelet and thrombin activity improves the
      extent and duration of rTPA-induced thrombolysis in the electrolytic canine
      model. Furthermore, our findings suggest that low doses of platelet IIb/IIIa and
      direct thrombin antagonists in combination may be used successfully during
      thrombolysis.

PMID- 8149547
TI  - Functional improvement precedes structural regression of atherosclerosis.
AB  - BACKGROUND: Vasoconstrictor responses to serotonin are augmented in monkeys with
      diet-induced atherosclerosis and improve after 18 months of normal diet. We
      tested the hypothesis that functional improvement may occur early during
      regression, before evidence of structural improvement. METHODS AND RESULTS:
      Responses of the iliac artery to serotonin were measured by quantitative
      angiography and a Doppler flow probe in several groups of monkeys: (1) normal
      monkeys, (2) monkeys fed an atherogenic diet for 2 years (atherosclerotic), and
      (3) monkeys fed an atherogenic diet for 2 years (preregression) followed by a
      normal diet for 4, 8, or 12 months (regression). In normal monkeys, serotonin
      produced minimal constriction of the iliac artery, and blood flow to the legs
      increased. In atherosclerotic monkeys, there was pronounced constriction of the
      iliac artery, and blood flow to the legs decreased markedly. After 4 months of
      regression diet, four of eight monkeys demonstrated marked reduction in
      hyperresponsiveness to serotonin angiographically, and by 8 months, six of eight
      monkeys had significant improvement. After regression, serotonin produced minimal
      changes in flow. There was no reduction in intimal area (ie, atherosclerotic
      lesion) in iliac arteries from regression monkeys compared with atherosclerotic
      monkeys, but there was a marked reduction in cholesteryl ester in arteries from
      regression monkeys. CONCLUSIONS: Abnormal vasoconstrictor responses to serotonin
      usually return to or toward normal within a few months during regression of
      atherosclerosis. Functional improvement occurs in conjunction with early
      resorption of lipid from the arterial wall and occurs before detectable changes
      in mass of the atherosclerotic lesion.

PMID- 8149548
TI  - Intracoronary versus intravenous effects of cocaine on coronary flow and
      ventricular function.
AB  - BACKGROUND: Cocaine use has been associated with cardiomyopathy and ischemic
      coronary syndromes. However, the pathophysiological mechanisms responsible for
      these syndromes are not clear and have been suggested to involve direct effects
      of cocaine on myocyte contractility and coronary resistance as well as indirect
      effects via altered autonomic tone, secondary mediators, and myocardial
      metabolism. We sought to distinguish direct from indirect effects of cocaine on
      ventricular function and coronary resistance by comparison of the administration
      of intracoronary cocaine (0.12 to 0.36 mg/min constant infusion) with intravenous
      cocaine (5 mg/kg bolus infusion) in an in vivo anesthetized pig preparation.
      METHODS AND RESULTS: To control for changes in coronary resistance secondary to
      autoregulation and myocardial metabolism, the left anterior descending coronary
      artery was perfused at constant coronary pressure and the interventricular vein
      was cannulated for coronary venous oxygen saturation measurement. Coronary blood
      flow, regional percent segment shortening, myocardial oxygen consumption, and
      serum cocaine concentrations were measured. Intracoronary cocaine produced a dose
      dependent decrease in percent segment shortening in the absence of significant
      changes in coronary flow or systemic hemodynamics. In contrast, intravenous
      cocaine had mild biphasic effects on coronary resistance with an initial brief
      vasodilation (30.0 +/- 5% increase in flow from control) followed by more
      prolonged vasoconstriction (17.0 +/- 3.3% decrease in flow from control), which
      were independent of autoregulation or myocardial metabolism. In addition,
      intravenous cocaine caused an early 48% decrease in percent segment shortening,
      at which time the measured cocaine concentration was 20.1 micrograms/mL blood.
      This was comparable to the intracoronary cocaine concentration of 17.1
      micrograms/mL blood, which produced a similar 48% decrease in percent segment
      shortening. CONCLUSIONS: We conclude that the effects of acute cocaine exposure
      on ventricular function are predominantly direct but of brief duration and
      therefore probably not clinically relevant. The effects of cocaine on coronary
      tone are predominantly indirect and biphasic, with early vasodilation followed by
      mild and more prolonged vasoconstriction. In the absence of coronary stenosis or
      ventricular hypertrophy, this small amount of vasoconstriction is unlikely to
      cause ischemia.

PMID- 8149549
TI  - In vivo assessment of left atrial contractile performance in normal and
      pathological conditions using a time-varying elastance model.
AB  - BACKGROUND: Contractile function of the ex vivo, isolated left atrium (LA) has
      been described by a time-varying elastance, but this atrial chamber property has
      not been shown in vivo. METHODS AND RESULTS: Instantaneous LA pressure-volume (P
      V) relations were studied in 12 anesthetized, autonomically blocked, atrially
      paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a
      cast-validated formula. Data were collected during increases in LA pressure
      produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V
      points from 5 beats, representing a wide range of atrial pressures, were fitted
      by linear regression analysis (range of R2, .92 to .99). There were significant
      time-dependent increases in the slopes [E(t)] and small but statistically
      insignificant decreases in the volume axis intercepts [VO(t)] of the
      instantaneous LA P-V relations during atrial contraction; maximal elastance
      (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA
      volume). Emax was not significantly different than the slopes of either the
      nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V
      relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL,
      respectively. In 7 dogs, data were collected both before and after a rapid
      infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a
      calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL,
      P < .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/-
      1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6
      mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume
      was significantly greater than and elastance determinations were similar to those
      of normal dogs. However, the effects of calcium infusion on LA function were
      attenuated in these animals. CONCLUSIONS: We conclude that (1) in the intact
      heart, LA contraction may be approximated by time-varying elastance with time
      dependent changes in E(t) and that (2) LA systolic P-V relations using either the
      nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of
      Emax, are highly linear and sensitive to calcium-induced changes in inotropic
      state, and may be useful in identifying LA chamber adaptation to chronic
      hemodynamic loads.

PMID- 8149550
TI  - Mortality benefits and the implantable cardioverter-defibrillator.
AB  - The automatic implantable cardioverter-defibrillator (ICD) is highly effective in
      reducing sudden death rates in patients with life-threatening ventricular
      tachyarrhythmias. However, the magnitude of the ability of the ICD to improve
      overall survival is less certain. Data supporting the contention that the ICD
      prolongs survival are reviewed. It is evident that the mortality benefit
      consequent to the marked reduction in sudden death varies widely across
      subpopulations in a predictable manner. This observation reflects the powerful
      influence of other clinical factors that constrain survival in typical ICD
      patients. The implications for future studies on the ICD are discussed.

PMID- 8149551
TI  - Evaluating the potential cost-effectiveness of stenting as a treatment for
      symptomatic single-vessel coronary disease. Use of a decision-analytic model.
AB  - BACKGROUND: Coronary stenting appears to provide more predictable immediate
      results and lower rates of restenosis than conventional balloon angioplasty for
      selected lesion types, but its hospital costs are significantly higher. This
      study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz
      coronary stenting relative to conventional balloon angioplasty for the treatment
      of patients with symptomatic, single-vessel coronary disease. METHODS AND
      RESULTS: We developed a decision-analytic model to predict quality-adjusted life
      expectancy and lifetime treatment costs for patients with symptomatic, single
      vessel coronary disease treated by either Palmaz-Schatz stenting (PSS) or
      conventional angioplasty (PTCA). Estimates of the probabilities of overall
      procedural success (PTCA, 97%; PSS, 98%), abrupt closure requiring emergency
      bypass surgery (PTCA, 1.0%; PSS, 0.6%), and angiographic restenosis (PTCA, 37%;
      PSS, 20%) were derived from review of the literature published as of September
      1993. Procedural costs were based on the true economic (ie, variable) costs of
      each procedure at Boston's Beth Israel Hospital. On the basis of these data,
      coronary stenting was estimated to result in a higher quality-adjusted life
      expectancy than conventional angioplasty but to incur additional costs as well.
      Compared with conventional angioplasty, stenting had an estimated incremental
      cost-effectiveness ratio of $23,600 per quality-adjusted life year gained.
      Although the cost-effectiveness ratio for stenting changed with variations in
      assumptions about the relative costs and restenosis rates, it remained less than
      $40,000 per quality-adjusted year of life gained--and thus was similar to many
      other accepted medical treatments--unless the stent angiographic restenosis rate
      was > 23%, the angioplasty restenosis rate was < 34%, or the cost of stenting
      (including vascular complications) exceeded that of conventional angioplasty by
      more than $3000. The alternative strategy of secondary stenting (initial
      angioplasty followed by stenting only for symptomatic restenosis) was estimated
      to be both less effective and less cost-effective than primary stenting over a
      wide range of plausible assumptions and thus does not appear to be cost-effective
      when primary stenting is also an option. CONCLUSIONS: Decision-analytic modeling
      can be used to evaluate the potential cost-effectiveness of new coronary
      interventions. Our analysis suggests that despite its higher cost, elective
      coronary stenting may be a reasonably cost-effective treatment for selected
      patients with single-vessel coronary disease. Primary stenting is unlikely to be
      cost-effective for lesions with a low probability of restenosis (eg, < 30%) or
      for patients for whom the cost of stenting is expected to be much higher than
      usual (eg, because of a high risk of vascular complications). Given the
      sensitivity of the cost-effectiveness ratios to even modest variations in the
      relative restenosis rates and cost estimates, future studies will be necessary to
      determine more precisely the cost-effectiveness of coronary stenting for specific
      patient and lesion subsets.

PMID- 8149552
TI  - James B. Herrick Memorial Lecture.

PMID- 8149553
TI  - Twenty-six-year-old Hispanic woman with no medical history presents with
      pleuritic chest pain.

PMID- 8149555
TI  - Key references on thrombolytic therapy 1983-1993.

PMID- 8149554
TI  - Images in cardiovascular medicine. Lymphocytic myocarditis.

PMID- 8149556
TI  - The role of clinical trials in the Food and Drug Administration approval process
      for cardiovascular devices.

PMID- 8149557
TI  - Cardiovascular devices and the Food and Drug Administration.

PMID- 8149558
TI  - Progressive left ventricular dysfunction and remodeling after myocardial
      infarction.

PMID- 8149559
TI  - Meaning of ejection fraction after subendocardial resection.

PMID- 8149560
TI  - Chronic myocardial hibernation.

PMID- 8149561
TI  - Ultrafast computed tomography in coronary screening.

PMID- 8149562
TI  - Assessment of peripheral vascular disease in diabetics.

PMID- 8149563
TI  - Intraclass correlation coefficient rather than correlation coefficient to examine
      agreements among different methods measuring valvular area.

PMID- 8149564
TI  - Induction of right ventricular hypertrophy with obstructing balloon catheter.

PMID- 8149565
TI  - Blunted nocturnal fall in blood pressure in hypertensive women.

PMID- 8149566
TI  - Clinical competence in insertion of a temporary transvenous ventricular
      pacemaker. A statement for physicians from the ACP/ACC/AHA Task Force on Clinical
      Privileges in Cardiology.

PMID- 8149567
TI  - Clinical competence in invasive cardiac electrophysiological studies. A statement
      for physicians from the ACP/ACC/AHA Task Force on Clinical Privileges in
      Cardiology.

PMID- 8149568
TI  - An objective and subjective comparative analysis of diffractive and front surface
      aspheric contact lens designs used to correct presbyopia.
AB  - As bifocal contact lenses have evolved, increasing emphasis has been placed on
      producing designs that are less dependent on such variables as pupil size and
      lens centration and movement. We evaluated these and other variables in 25
      presbyopic patients who underwent consecutive 1-week trials, wearing two
      different contact lens types: a diffractive lens and a front surface aspheric
      lens. Distance and near visual acuities were not significantly reduced by either
      lens type, and both exhibited binocular summation. With each lens design, visual
      acuity remained relatively independent of pupil size and small degrees of lens
      decentration. Contact lens movement with the aspheric design was associated with
      subjective fluctuations in vision to a greater extent than with the diffractive
      design. Contrast sensitivity was also measured and found to be reduced with the
      diffractive lens but not significantly altered by the aspheric lens. Overall,
      only two patients could not be successfully fit with either lens type. After 6
      months, 21 patients (84%) reported successful lens wear with their chosen lens
      type.

PMID- 8149569
TI  - Clinical evaluation of Purilens, an ultraviolet light contact lens care system.
AB  - Purilens is a new contact lens care system that uses ultraviolet light and
      subsonic turbulence for lens cleaning and disinfection. In a single hands-off
      process using only preservative-free sterile saline, the lenses are ready to wear
      after a 15-minute cycle. This study was designed to test the safety of this
      contact lens care system. A total of 84 contact lens wearers from six centers
      were enrolled in the 3-month study, which comprised an initial visit and follow
      up visits at 1, 2, 4, 8, and 12 weeks. At the end of the study, lenses and units
      were collected and a questionnaire was completed. Seventy-six of the 84 subjects
      (168 eyes) completed the study. No severe eye complications were reported, and no
      patients were removed from the study because of ocular problems or complications
      associated with the device or its use. Four patients were removed from the study
      for noncompliance with follow-up. Another four patients were active for 2 months,
      but were requested by the sponsor to complete the study 1 month early to complete
      data collection. Patient satisfaction was high. The study suggests that Purilens
      may be considered as an alternative for contact lens cleaning and disinfection.

PMID- 8149570
TI  - Alteration of corneal asphericity in rigid gas permeable contact lens induced
      warpage.
AB  - We developed the corneal asphericity index (CAI), which indicates the asphericity
      of the central cornea using the TMS-1 videokeratoscope, and used the CAI to
      evaluate both normal corneas and corneas with rigid gas permeable (RGP) lens
      induced warpage. The CAI (mean +/- standard deviation) for the 22 control corneas
      was 0.33 +/- 0.26, which indicates that the normal central cornea has a prolate
      shape. The average CAI for the 24 corneas with RGP lens induced warpage was
      significantly lower (-0.15 +/- 0.36, P = 0.0001). These data suggest that some
      corneas have abnormal asphericity in the central cornea when warpage occurs with
      RGP lenses. CAI is useful for the quantitative assessment of asphericity and
      topographic abnormalities in the central cornea caused by contact lens induced
      warpage.

PMID- 8149571
TI  - Contamination of disinfection solution bottles used by contact lens wearers.
AB  - We investigated the contamination of disinfection solution bottles after 2 weeks
      of patient use. Forty-four subjects participated in the study and each used three
      soft lens care systems (cross-over study). The order in which the three care
      systems were dispensed was randomized to eliminate systematic bias. Sixteen
      subjects used only one of the systems (disinfection solutions) over three
      consecutive 2-week periods (reliability study). Contamination of the disinfection
      solution bottles occurred in 12 of the 180 bottles sampled (7%), and the level of
      contamination of these bottles ranged up to 10(5) colony forming units per
      milliliter. A wide range of microorganisms was identified in these positive
      samples, many of which were potential ocular pathogens. None of the subjects in
      the study (n = 60) showed contamination in more than one of the three solution
      bottles sampled, suggesting that the phenomenon was not strongly patient
      specific. The rate of contamination of disinfection solution bottles was not
      influenced by contact lens wearing experience (i.e., familiarity with care
      procedures), by the time of year (season) at which the samples were collected, or
      by the subjects' compliance with hand washing. However, among the 44 subjects in
      the cross-over study, the rate of contamination of disinfection solution bottles
      was influenced by the type of disinfection solution.

PMID- 8149572
TI  - FluoroPerm 151 extended wear: a clinical study.
AB  - In this 3-month study, 132 (81.5%) of 162 eyes (81 subjects) successfully wore
      FluoroPerm 151 RGP lenses on an extended wear schedule. Fifty-nine (72.8%)
      subjects were adapted RGP lens wearers; 3 (3.7%) were polymethylmethacrylate
      (PMMA) lens wearers; 12 (14.8%) were current hydrogel lens wearers; and 7 (8.6%)
      had no previous contact lens experience. Throughout the study, no significant
      physiologic or pathologic concerns were found or led to lens discontinuation.
      Among the 30 eyes that discontinued the study, there were no serious health
      concerns; the chief reason for discontinuing lens wear was discomfort. Study
      results seemed to indicate that little, if any, physiologic stress was induced by
      extended wear of the FluoroPerm 151 lenses. The overall clinical success with the
      FluroPerm 151 lenses can be attributed to the material's high level of oxygen
      flux and compatible surface characteristics.

PMID- 8149573
TI  - Electron microscopic findings in a cornea with recurrence of herpes simplex
      keratitis after excimer laser phototherapeutic keratectomy.
AB  - Excimer laser phototherapeutic keratectomy is emerging as an alternative therapy
      to corneal transplantation for the treatment of multiple corneal diseases. We
      report three cases of recurrence of herpes simplex keratitis after treatment of
      herpetic corneal scars with the excimer laser. In two cases, the patients
      underwent subsequent corneal transplantation. One corneal button examined with
      transmission electron microscopy (TEM) demonstrated a well-differentiated
      epithelium over the area of ablation, a linear, continuous basal lamina, and no
      viral particles. Anterior stromal scarring may have resulted from the laser
      treatment itself or may represent incomplete ablation of previous scars. Whether
      reactivation of the virus was stimulated by the laser or occurred as part of the
      natural history of the disease is uncertain. We recommend that patients who
      undergo excimer laser treatment for herpes simplex scarring receive careful
      follow-up including antiviral coverage.

PMID- 8149574
TI  - Histopathologic evaluation of stromal inflammation in Acanthamoeba keratitis.
AB  - Ten corneal specimens obtained at the time of penetrating keratoplasty for long
      standing refractory Acanthamoeba keratitis were reviewed. Histopathologic
      findings included epithelial denudation and variable degrees of necrosis,
      inflammation, and cysts or trophozoites of acanthamoeba in the stroma. No blood
      vessels were found in the stroma despite the presence of long-standing corneal
      inflammation. The absence of corneal stromal neovascularization on biomicroscopic
      and histopathologic examination is a sign of Acanthamoeba keratitis.

PMID- 8149575
TI  - Keratoconjunctivitis sicca in female patients infected with human
      immunodeficiency virus.
AB  - We recently reported keratoconjunctivitis sicca (KCS) occurring as a single
      entity in approximately 20% of male patients testing positive for human
      immunodeficiency virus (HIV). In a subsequent study of HIV-positive females (n =
      59; age range: 23 to 42 years), ten were found to have clinical signs and
      symptoms of KCS. The Schirmer test without anesthetic was performed on these
      patients, as well as on ten HIV negative females in the same age range. Reported
      as mean +/- 1 standard deviation, the result of the Schirmer test was 5.6 +/- 4.1
      mm of wetting in the HIV-positive group, and 15.6 +/- 7.8 mm of wetting in the
      control group. The mean tear osmolarity test value of the HIV-positive patients
      was 318.8 +/- 9.5 mOsm/L, with 18 of the 20 suspect eyes testing positive for
      KCS. The tear osmolarity value among the female control patients was 304.1 +/-
      5.9 mOsm/L, with one of the 20 eyes testing positive for KCS. We conclude from
      the data that KCS occurs at a significantly greater rate in HIV positive females
      than in the general population.

PMID- 8149576
TI  - The effects of soft contact lens disinfection solutions on rabbit corneal
      epithelium.
AB  - This investigation compared the effects of three commercial soft contact lens
      solutions on the rabbit corneal epithelium. Fifteen rabbits wore lenses soaked in
      ReNu multi-purpose disinfecting solution, Opti-Free rinsing, disinfecting and
      storage solution, and neutralized AOSEPT for a period of 30 minutes. Control eyes
      wore lenses soaked in unpreserved saline for the same time period. Corneas were
      photographed by scanning electron microscopy and graded in random locations
      across the corneal surface. Slides of these photographs were projected at a
      magnification of x3000 and graded according to two scales by an observer unaware
      of the treatment used. The results showed a significant treatment effect, with
      all three experimental solutions scoring higher than controls. When the three
      experimental solutions were compared, corneas exposed to ReNu multi-purpose
      disinfecting solution showed a significantly increased effect by contingency
      table analysis of data from the adapted Burstein's scale.

PMID- 8149577
TI  - Enhancements to the conjunctival impression cytology technique and examples of
      applications in a clinico-biochemical study of dry eye.
AB  - The conjunctival impression cytology (CIC) technique was optimized for cell pick
      up and resolution of cytologic detail. Use of surfactant-free smaller pore-size
      Millipore filters yielded consistently high cell pick-up and resolution of cell
      detail. Staining by the modified Papanicolaou technique in a free-floating format
      allowed quantitative evaluation of cytologic features. Air exposure of CIC
      specimens for up to 8 minutes before fixing (as occurs with Nelson's standardized
      technique) did not adversely affect cell appearances. The optimized method was
      applied to a group of 50 patients with dry eyes. CIC features were correlated
      with symptoms, clinical test results, and serum and tear protein levels of dry
      eye patients.

PMID- 8149578
TI  - Automobile manufacturing: is there a lesson here for the RGP contact lens
      industry?

PMID- 8149579
TI  - Corneal stem cell disease: concepts, categorization, and treatment by auto- and
      homotransplantation of limbal stem cells.

PMID- 8149580
TI  - Extended wear contact lenses: boon or bane?

PMID- 8149581
TI  - Developmental plasticity of the rat olfactory receptor sheet as shown by complete
      recovery of surface area and cell number from extensive early hypothyroid growth
      retardation.
AB  - To assess the effects of early thyroid deficiency, and recovery from this
      condition on growth and development of olfactory epithelium (OE), male Sprague
      Dawley rat pups were rendered hypothyroid by addition of propylthiouracil (PTU)
      to their drinking water from birth. At weaning some rats continued to receive PTU
      while others ere allowed to recover by withdrawal of PTU. Body weights and plasma
      thyroxine levels were determined in all groups. At the ages of 25, 50 and 90
      days, the OE of these hypothyroid and 'recovery' rats were compared with age
      matched controls for surface area, epithelial thickness, density and total number
      of olfactory receptor neurons, basal cells and supporting cells, using
      morphometric and cell counting methods. Normal rats showed marked and highly
      significant increases in the OE surface area and olfactory neuron number (2.6-
      and 2.3-folds) during the post-weaning period. In the hypothyroid rats, body
      growth and thyroxine levels were severely suppressed. The OE in the 25-day-old
      hypothyroid rats showed more than 40% reduction in surface area and cell number,
      compared to controls, but mean epithelial thickness and surface density of cells
      were unchanged. In the post-weaning hypothyroid rats, the expansion of surface
      area was severely retarded, and increase in cell number ceased entirely. In rats
      allowed to recover by PTU withdrawal, by 90 days of age, body weight and size had
      markedly increased but had not caught up completely; however, thyroxine levels
      were restored to normal and the surface area and cell number in the OE had
      increased in a compensatory manner, completely restoring the deficiencies in OE
      growth, including surface area, numbers of receptor neurons, basal cells and
      supporting cells. The results indicate marked growth plasticity of OE in the post
      weaning rats. This pronounced ability to recover from early growth retardation
      contrasts with that seen in central neural structures, and indicates the great
      potential of OE for use as a model neural system for the study of recovery from
      early damage and growth retardation.

PMID- 8149582
TI  - Changes in protein expression associated with the developmental transition from
      permissive to restrictive states of spinal cord repair in embryonic chick.
AB  - In this study we examined protein changes accompanying a developmental loss of
      axon regeneration in the spinal cord occurring around embryonic day 13 (E13) of
      spinal cord development in the chick. We employed high resolution two-dimensional
      (2D) gel electrophoresis to identify proteins consistently altering their
      expression around this critical period. Spinal cord protein fractions were
      isolated from E8, E10, E12, E14, E16, E18 and post-hatching day 2 spinal cord and
      separately run on a high resolution 2D gel system. Protein spots were visualized
      with silver staining and subsequently analyzed. Ten proteins were identified,
      termed developmental spinal cord proteins (DSPs), with five increasing and five
      decreasing their abundance over the developmental period studied. Apparent
      molecular weight and isoelectric points have been calculated and are reported.
      Further studies, currently underway, will be required to determine if these
      identified proteins are involved in the developmental loss of regenerative
      ability.

PMID- 8149583
TI  - Retinohypothalamic tract development in the hamster and rat.
AB  - The development of the retinohypothalamic tract (RHT) in the albino rat and
      golden hamster was studied using anterograde transport of cholera toxin
      conjugated to horseradish peroxidase (CT-HRP). The RHT has three components in
      the adult: (1) a dense projection to the ventrolateral subdivision of the
      suprachiasmatic nucleus (SCN) with some fibers extending into the dorsomedial
      SCN; (2) a projection to adjacent areas, the anterior hypothalamic area (AHA) and
      retrochiasmatic area (RCA) and in the hamsters, into the preoptic area (POA); (3)
      a projection to the lateral hypothalamic area (LHA). In the rat, the projection
      to the SCN and adjacent areas first appears as scattered varicosities at the
      ventral border of the SCN at postnatal day 1 (P1) and gradually increases until
      the adult pattern is achieved at approximately P10. The projections to the AHA
      and RCA are seen first at P2-P3 and gradually increase to the adult appearance by
      P15. Both the projection to the SCN and adjacent areas and to the LHA, initially
      are more extensive than in the adult. Many of the axons extend well beyond the
      zone of the adult pattern but these anomalous fibers are eliminated by P6-P10.
      The LHA projection first appears at embryonic day 21-22 (E 21-22) and gradually
      increases in density from P1-P6. In the hamster the projections to the SCN, AHA
      and LHA appear first on P4 and gradually increase in density to reach the adult
      pattern by P15. The projections to the RCA and POA are present by P6 and reach
      the adult pattern by P15. None of the RHT projections in the hamster has the
      initial extended growth followed by pruning back that characterizes RHT
      development in the rat. Thus, the development of the RHT in both the rat and the
      hamster is complex with components of the projection appearing at different times
      with differing patterns of development that indicate specialized interactions of
      the developing axons with their target neurons. Synaptogenesis in the hamster
      hypothalamus was analyzed using an antiserum to synapsin I. Few synapses are
      present at E16, the last day of gestation, in the LHA, SCN and AHA. From P1-P3,
      synaptogenesis proceeds rapidly and the adult pattern is achieved in all three
      areas by P4.

PMID- 8149584
TI  - Regulation of cell division and rod differentiation in the teleost retina.
AB  - We tested the effects of several growth factors on the proliferation and
      differentiation of cells in the teleost retina which typically become rod
      photoreceptors to understand their regulation. Using organotypic slice cultures
      of differentiated teleost fish retinal tissue, we found that insulin and insulin
      like growth factor I (IGF-I) stimulate proliferation of rod precursor cells
      whereas basic fibroblast growth factor (bFGF) does not. In the presence of bFGF,
      however, a greater proportion of the cells that had divided expressed a rod
      photoreceptor-specific phenotype than did control slices. This suggests insulin
      and the related IGF-I can influence the regulation of neuronal cell division
      whereas bFGF promotes the differentiation of neuronal stem cells into rod
      photoreceptors in retinal slice culture. These results support the idea that cell
      division and differentiation are differentially regulated and diffusible factors
      play a role in this process.

PMID- 8149585
TI  - Opiates selectively increase intracellular calcium in developing type-1
      astrocytes: role of calcium in morphine-induced morphologic differentiation.
AB  - Endogenous opioids and opiate drugs inhibit nervous system maturation, in part,
      by affecting the growth of astrocytes. Opiates inhibit astrocyte proliferation
      and cause premature differentiation. The emerging importance of Ca2+ in astrocyte
      function prompted us to explore whether opiates might affect astrocyte
      development by altering Ca2+ homeostasis. Astrocyte-enriched cultures were
      derived from newborn ICR mouse cerebra. Quantitative fluorescent measurements of
      intracellular free Ca2+ ([Ca2+]i) using Fura-2 as well as fluo-3 and computer
      aided image analysis showed that 1 microM morphine significantly increased
      [Ca2+]i in flat, polyhedral, glial fibrillary acidic protein (GFAP)
      immunoreactive astrocytes at 2 and 6 min, and at 72 h. Co-administration of 3
      microM naloxone blocked morphine-dependent increases in [Ca2+]i. Treatment with 1
      microM concentrations of the kappa-opioid receptor agonist, U69,593, but not
      equimolar amounts of mu ([D-Ala2,MePhe4,Gly(ol)5]enkephalin)- or delta ([D-Pen2,D
      Pen5]enkephalin)-opioid receptor agonists, significantly increased [Ca2+]i in
      astrocytes. To assess the role of Ca2+ in morphine-induced astrocyte
      differentiation, untreated and 1 microM morphine-treated astrocyte cultures were
      incubated for 5 days in < 0.01, 0.3, 1.0, or 3.0 mM extracellular Ca2+ ([Ca2+]o),
      or incubated with 1.0 mM [Ca2+]o in the presence of 1 microM of the Ca2+
      ionophore, A23187. The areas of single astrocytes were measured and there was a
      positive correlation between astrocyte area and [Ca2+]o. Morphine had an additive
      effect on area and form factor measures when [Ca2+]o was 1.0 mM. High [Ca2+]o
      (3.0 mM) alone mimicked the action of morphine. Morphine alone had no effect on
      astrocyte area in the presence of 3.0 mM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149586
TI  - Regional cerebral blood flow response to acute hypoxia changes with postnatal age
      in the rat.
AB  - The quantitative autoradiographic [14C]iodoantipyrine technique was applied to
      measure the effects of an acute hypoxic exposure on rates of local cerebral blood
      flow (LCBF) in the 10 (P10)-, 14 (P14)- and 21 (P21)-day-old rat. The animals
      were exposed to hypoxic (7% O2/93% N2) or control gas mixtures (21% O2/79% N2)
      for 40 min before the initiation of the 1-min LCBF measurement. At P10, hypoxia
      induced a 142-415% increase in LCBF over control levels, which affected the 45
      structures studied. The highest increases in LCBF were noticed in posterior
      midbrain and brainstem regions. These increases are in good accordance with
      hypoxia-induced increases in LCBF recorded during acute hypoxia exposure in both
      newborn and adult animals. At P14 and P21, rates of LCBF decreased with hypoxia.
      These decreases were significant in 23 and 21 brain regions, respectively,
      belonging to all systems studied. These changes in LCBF are in quite good
      correlation with our previous data on the effects of acute hypoxia exposure on
      cerebral glucose utilization but the decrease in LCBF is of higher amplitude than
      the one in cerebral glucose utilization translating into a relative hypoperfusion
      at a constant metabolic level at P14 and P21. However, arterial blood pressure
      was reduced by 16 mmHg and arterial pCO2 was significantly decreased at the two
      latter ages in hypoxic animals compared to controls. These two systemic factors,
      and mainly hypocapnia, are rather responsible for the cerebral hypoperfusion
      recorded at P14 and P21 in hypoxic rats whereas the circulatory response seems to
      be predominantly hypoxic at P10.

PMID- 8149587
TI  - The 'creeper stage' in cerebellar climbing fiber synaptogenesis precedes the
      'pericellular nest'--ultrastructural evidence with parvalbumin
      immunocytochemistry.
AB  - In perinatal rats, neurons in the dorsal cap of the inferior olivary complex
      transiently express parvalbumin-immunoreactivity (PA-IR). Their terminal axonic
      fields, particularly in the flocculonodular lobe, appear as precise bands of fine
      and convoluted immunostained fibers extending over the Purkinje plate and the
      nascent molecular layer. Thicker PA-IR fibers, corresponding to vestibular
      fibers, are observed only under the Purkinje plate. Electron microscopic analysis
      of the PA-IR climbing fibers within the bands allowed us to study their
      synaptogenesis with Purkinje cells. At birth (P0), thin PA-IR climbing fiber
      axons creep over these immature neurons following the contours of their perikarya
      and dendrites. They establish a few synaptic contacts, some of them of mature
      appearance, upon the smooth surface of Purkinje cell apical dendrites. PA-IR
      axonal growth cones are observed in the upper portion of the molecular layer.
      This precocious stage of climbing fiber/Purkinje cell synaptogenesis has been
      named here the 'creeper' stage. After the regression of the Purkinje cell apical
      dendrites (by P5), PA-IR climbing fibers are perisomatically located and synapse
      on Purkinje cell somatic protrusions, forming the classical pericellular 'nests'.
      The presence of mature synapses at P0 indicates the precocity of climbing
      fiber/Purkinje cell synaptogenesis and suggests its fetal onset. Therefore, this
      process of synaptogenesis occurs in two steps: (i) an early transient one,
      simultaneous with the initiation of the formation of the olivocerebellar map,
      that could be involved in the maintenance of the nascent topography of the
      projection and (ii) a latter step which concerns the refinement of the projection
      within a given PA-IR band through the regression of multiple innervation of
      Purkinje cells by climbing fibers, step which brings the required synaptic
      specificity to the adult olivocerebellar system.

PMID- 8149588
TI  - Continued search for the cellular signals that regulate regeneration of
      dopaminergic neurons in goldfish retina.
AB  - Intraocular injections of low doses (0.7-1.4 mM estimated intraocular
      concentration) of 6-hydroxydopamine (6OHDA) selectively destroy dopaminergic
      neurons in the inner nuclear layer (INL) of goldfish retina, and they never
      regenerate. However, injection of a higher dose of 6OHDA (2.9 mM) destroys > 30%
      (but not all) of the cells in both the INL and the outer nuclear layer (ONL), but
      within 3 weeks, neurons in both the INL (including dopaminergic neurons) and the
      ONL regenerate. We hypothesize that the regenerated neurons derive from mitotic
      rod precursors in the ONL and that damage to the surrounding micro-environment
      (i.e. destruction of photoreceptors) triggers the regenerative response. To
      directly test this hypothesis, we selectively ablated > 99% of dopaminergic
      neurons (with low doses of 6OHDA) and up to 55% of rod photoreceptors (with
      tunicamycin), and asked whether the dopaminergic neurons regenerated, as
      evidenced by double immunolabeling with anti-tyrosine hydroxylase and anti
      bromodeoxyuridine. After 38 days, the number of bromodeoxyuridine-immunoreactive
      rod nuclei was increased 2.4-fold compared to controls, but no regenerated
      dopaminergic neurons were found. These data suggest that although the rate of rod
      production increases, rod precursors do not alter their normal pathway of
      development to replace dopaminergic neurons in the INL when damage to the ONL is
      limited to destruction of rods.

PMID- 8149589
TI  - Dose-related effects of a neonatal 6-OHDA lesion on SKF 38393- and m
      chlorophenylpiperazine-induced oral activity responses of rats.
AB  - Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with
      concurrent supersensitization of dopamine (DA) D1 and serotonin 5-HT1C receptors,
      for agonist-induced oral activity. The present study was conducted to determine
      if graded reduction of striatal DA content and/or graded elevation of striatal 5
      HT content by 6-OHDA would alter sensitivity of either receptor type, and thereby
      influence oral activity responses to DA and 5-HT agonists. At 3 days after birth,
      groups of rats were pretreated with desipramine (20 mg/kg i.p.), 1 h before
      administration of a range of doses of 6-OHDA HBr (15, 30, 60, 100, 150 and 200
      micrograms, i.c.v., salt form; half in each lateral ventricle) or the vehicle,
      saline (0.85%)-ascorbic acid (0.1%). Between 2 and 4 months, a series of
      challenge doses of SKF 38393 HCl (0.30 to 3.0 mg/kg i.p.) and m
      chlorophenylpiperazine 2HCl (0.30 to 6.0 mg/kg i.p.; m-CPP 2HCl) were
      administered to each group of rats and oral activity was observed. Oral activity
      was determined for 1 min every 10 min during a 60-min period, starting 10 min
      after injection of agonist or vehicle. SKF 38393 dose-response curves
      demonstrated enhanced oral activity responses in rats lesioned neonatally with
      150 or 200 micrograms of 6-OHDA. m-CPP dose-response curves demonstrated enhanced
      oral activity responses in these 2 groups of rats, as well as those lesioned
      neonatally with 100 micrograms of 6-OHDA. Striatal DA content was reduced by >
      97% in these 3 groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149590
TI  - Prenatal exposure to methadone delays the development of striatal cholinergic
      neurons.
AB  - The effect of prenatal exposure to methadone via maternal osmotic minipumps on
      the expression of acetylcholinesterase (AChE) and choline acetyltransferase
      (ChAT) has been studied by light microscopy in the striatum of male and female
      rats. At postnatal day 10, rats of both sexes exhibit reduced intensity of ChAT
      immunoreactive staining in striatal neurons in the methadone-treated group in
      comparison to either untreated or water-treated controls. Although the number and
      distribution of ChAT-immunoreactive neurons appear to be similar across all three
      groups, the size (cross-sectional area) of these neurons is significantly smaller
      in the methadone-treated animals. By postnatal day 22, there are no differences
      in the ChAT immunoreactivity of striatal neurons between the water-treated and
      methadone-treated animals. The size of these neurons in female animals of both
      treatment groups is significantly larger than those of male animals in the same
      groups at postnatal day 22. AChE histochemical staining is qualitatively similar
      between treatment groups in both age groups. Thus, prenatal exposure to methadone
      appears to produce a delay in the expression of ChAT in striatal neurons. It
      remains to be demonstrated whether these differences are a direct effect of
      methadone exposure or are a consequence of neonatal withdrawal.

PMID- 8149591
TI  - Microglial invasion and activation in response to naturally occurring neuronal
      degeneration in the ganglion cell layer of the postnatal cat retina.
AB  - Retinae of kittens between postnatal (P) days 2 and 10 were examined for the
      presence of degenerating neuronal profiles, normal nucleoli and microglia.
      Comparison of the numbers of degenerating profiles with numbers of axons lost
      from the optic nerve suggest that the majority of these profiles result from the
      degeneration of retinal ganglion cells. Analysis of local densities of the
      different profiles revealed different rates of cell loss, occurring at different
      times in central and peripheral retina. The period of rapid cell loss occurred
      between P2 and P3 in central retina compared to between P8 and P10 in peripheral
      retina. At both locations, these periods of rapid cell loss were accompanied by a
      decrease in the ratio of microglia to dying cells even though the absolute
      densities of microglia increased. However, calculation of the clearance times of
      cellular debris indicate that the speed of removal of degeneration products is
      greater during rapid cell loss, which suggests that cellular degeneration serves
      to activate the phagocytic process.

PMID- 8149592
TI  - Early in ovo exposure of chick embryos to ethanol prevents the neuronotrophic
      effects of intracerebral NGF administration on cholinergic phenotypic expression.
AB  - We have reported that ethanol administration during early neuroembryogenesis
      significantly alters neuronal phenotypic expression. In addition, previous
      findings have indicated that ethanol may interfere with the neurotrophic effects
      of NGF. In this study, we examined the cholinergic neuronal response to NGF given
      intracerebrally to embryos at embryonic day 8 (E8) which were exposed to ethanol
      in ovo via the air sac at E1-3. We found that doses of NGF ranging from 0.01 to 1
      ng/2 microliters/embryo given intracerebrally to untreated embryos at E8, and
      sacrificed at E10, significantly increased choline acetyltransferase (ChAT)
      activity, the marker for cholinergic neuronal expression. This response was most
      marked in spinal cord as compared with the low response observed in cerebral
      hemispheres. In control embryos treated with saline at E1-3 and then receiving
      NGF intracerebrally at E8, ChAT activity in the spinal cord increased with
      increasing NGF doses; the highest value was obtained with 0.1 ng NGF. In
      contrast, in ethanol-treated embryos, ChAT activity was not affected by
      intracerebral administration of NGF and, in fact, the highest dose (0.1 ng)
      produced a decrease in ChAT activity. We conclude that: (1) intracerebral
      administration of NGF produces differential cholinotrophic effects in the
      embryonic chick CNS; and (2) exposure to ethanol during early neuroembryogenesis
      interferes with the cholinotrophic effects of NGF.

PMID- 8149593
TI  - In vitro detection of calretinin immunoreactivity in chicken embryo dorsal root
      ganglion neurons: a possible developmental marker.
AB  - Calretinin, a cytosolic calcium-binding protein, is widely expressed in mammalian
      and chicken neurons, including subpopulations of dorsal root ganglion neurons. In
      chicken embryo spinal ganglion cells, calretinin first appears on the 9th day of
      incubation. To determine whether the expression of this protein is maintained in
      vitro and depends on the developmental stage, dissociated dorsal root ganglion
      cultures from chick embryos at E6 and E10 (before or after establishing
      connections) were processed for calretinin immunohistochemistry. Cultured neurons
      from E6 embryos never showed calretinin immunoreactivity at any culture duration,
      whereas neurons from E10 embryos displayed strong immunostaining immediately
      after attaching to the culture dish. Quantitative evaluation revealed that the
      percentage of calretinin-positive neurons increased until day 3 in culture and
      afterwards declined in parallel the total cell number. These results indicate
      that primary sensory neurons express calretinin in vitro similarly as in vivo and
      the gene expression depends from the establishment of connections with peripheral
      targets.

PMID- 8149594
TI  - Expression of versican mRNA is developmentally regulated in the brain of the
      embryonic chick and the developing rat.
AB  - RNA prepared from the brains of chick embryos at 12 days of incubation contained
      a 12-kb transcript that hybridized with a cDNA probe for the aggregating
      proteoglycan versican. No transcripts were detected in the brains of newborn rats
      while, at 3 days of postnatal development, three sizes of transcripts were
      present. None were detected in the 6-day old brain and, at later stages, the
      smallest transcript predominated.

PMID- 8149595
TI  - Gelsolin is localized in neuronal growth cones.
AB  - Gelsolin, a Ca(2+)-sensitive actin filament-severing protein, is involved in
      actin turnover. Immunocytochemical study with anti-gelsolin antibody revealed
      that the protein is localized in both filopodia and the body part of growth cones
      of differentiated PC12 cells with nerve growth factor (NGF) and of rat dorsal
      root ganglion neurons. Here, we identified gelsolin as one of the molecular bases
      for the Ca(2+)-dependent movement of growth cones.

PMID- 8149596
TI  - The glial fascicle: an ontogenic and phylogenic unit guiding, supplying and
      distributing mammalian cortical neurons.
AB  - Neurons destined for the mammalian neocortex migrate along radial glial cells
      (RGCs). This paper describes a comparative study of RGCs in the mouse, rat,
      hamster, cat and human fetus, selected as representative species of mammalian
      evolution. The glial fascicles display constant features throughout these
      species: they consist of 4-10 RGCs filled with glycogen. The glial fascicle
      guides and probably supplies metabolites to the migrating neurons and organizes
      the vertical lamination of the developing neocortical plate. The neuronal-glial
      unit which consists of the RGCs and their affiliated migrating neurons is
      conserved throughout the species studied, suggesting a designation as a
      phylogenic unit.

PMID- 8149597
TI  - Anomalous adrenalectomy-induced Fos-like immunoreactivity in the hypothalamic
      paraventricular nucleus of stress-hyporesponsive rats.
AB  - Cellular activity in the paraventricular nucleus of the hypothalamus (PVN) in
      response to adrenalectomy (ADX) and sham-ADX was measured in adult male rats,
      lactating females, and nursing pups using c-fos immunocytochemistry. Increased
      Fos-like immunoreactivity (FLI) was seen in the PVN of male rats at 4 h following
      ADX or sham-ADX but this increase was transient, and basal values were restored
      within 24 h. In suckling pups, ADX induced a marked FLI response in the PVN at 3
      days and at 18 days postpartum. At 11 days postpartum, however, the FLI response
      was attenuated relative to adult animals, and 3- and 18-day-old pups. Similarly,
      in nursing mothers, ADX induced FLI at 3 days, but this response disappeared by 7
      days and did not reappear by the end of the suckling period (day 21). These data
      indicate that c-fos expression is a sensitive indicator of hyporesponsiveness in
      the hypothalamic-pituitary-adrenal (HPA) system.

PMID- 8149598
TI  - Perinatal cocaine exposure inhibits the development of the male SDN.
AB  - The sexually dimorphic nucleus of the hypothalamus (SDN) is involved in sexual
      differentiation of the rat brain. Perinatal cocaine exposure was found to
      significantly reduce the volume of the male rat SDN (P < 0.001) while having no
      effect upon the volume of the female SDN. Pregnant dams and their pups were
      exposed to either saline, 7.5, 15, or 30 mg/kg of cocaine from gestational day 15
      through postnatal day 10. Litter size, pup weight, male-female sex ratio, and
      gross birth defects were unaffected, but maternal weight gain was significantly
      reduced in cocaine-treated dams. These findings imply that males perinatally
      exposed to cocaine during their critical period of SDN differentiation may
      exhibit compromised coital capabilities as well as impaired gonadotropin
      regulation.

PMID- 8149599
TI  - Morphine does not affect astrocyte survival in developing primary mixed-glial
      cultures.
AB  - In mixed-glial cultures, high concentrations of morphine (1 microM) have
      previously been shown to completely inhibit any increase in glial numbers,
      although DNA synthesis continues in flat, polyhedral astrocytes (type 1
      astrocytes). This suggests that high concentrations of morphine are toxic to
      glia. Morphine toxicity was assessed in mixed-glial cultures using calcein-AM and
      ethidium homodimer dyes as viability markers to identify live and dead cells,
      respectively. At 3, 5, and 7 days in vitro there was no significant difference in
      the number of dead cells between untreated and opiate-treated groups. Comparable
      numbers of ethidium homodimer-labeled cells were present in all groups. The
      greatest amount of cell death (16-19%) occurred at 3 days in vitro, while fewer
      cells (8-12%) were dying at 7 days in vitro. To further characterize the dying
      glia, glial fibrillary acidic protein (GFAP) and A2B5 immunocytochemistry were
      combined with viability markers. Only GFAP immunoreactive process-bearing cells
      and A2B5 immunoreactive cells (process-bearing cells and possibly some neurons)
      were dying in culture, whereas the death of flat, polyhedral GFAP-positive cells
      was not observed. Cell survival was not affected by morphine, but may be affected
      by culture conditions. Thus, morphine-induced reductions in glial numbers did not
      result from an increased rate of cell death. Collectively, the present and
      previous findings suggest that morphine inhibits the production of flat,
      polyhedral astrocytes solely by decreasing their rate of proliferation.

PMID- 8149600
TI  - Serum iron: would analytical improvement enhance patient outcome?

PMID- 8149601
TI  - Use of novel preparations of heparin to eliminate interference in ionized calcium
      measurements: have all the problems been solved?

PMID- 8149602
TI  - Clinical applications of gene therapy for cancer.
AB  - The number of gene therapy protocols for the treatment of cancer is growing
      rapidly. The most common type of approved clinical trial for cancer gene therapy
      involves the ex vivo gene transfer of cytokine genes (e.g., tumor necrosis
      factor, interleukin-2, granulocyte-macrophage colony-stimulating factor) into
      tumor cells. The idea behind this approach is to use gene transfer to induce a
      patient's tumor to become more immunogenic. The genetically altered tumor cells
      are reinjected into the patient in an effort to induce a systemic antitumor
      immune response against residual tumor cells. In other trials, investigators are
      using in situ gene transfer to selectively destroy cancer cells, sparing normal
      tissues. Continuing advances in molecular biology are likely to allow the
      development of new cancer treatments and methods of cancer prevention that will
      redefine cancer therapy.

PMID- 8149603
TI  - The fitting, acceptance, and processing of standard curve data in automated
      immunoassay systems, as exemplified by the Serono SR1 analyzer.
AB  - Methodologies for establishing standard curves on automated immunoassay systems
      are dependent on the computational capability of the instrument, its throughput,
      and, perhaps, the technical experience of the user. Here, factors constraining
      this approach are discussed in general and the procedures used for the Serono SR1
      analyzer are considered in detail. The SR1 is a moderate-throughput, fully
      automated immunoassay system capable of performing tests for (currently) 18
      analytes. The associated user-generated standard curves are utilized not only for
      interpolation of results but also for evaluation of system performance. The
      choices of curve-fitting method, weighting of data, acceptance criteria, and
      outlier rejection are taken out of the hands of the user and are made a vital and
      integral part of the system. I justify this approach and demonstrate how a
      sensible mathematical approach must be tailored to the configuration of the
      instrument.

PMID- 8149604
TI  - Enzymatic measurement of phosphatidylglycerol in amniotic fluid.
AB  - We describe an enzymatic method for measuring phosphatidylglycerol (PG) at
      concentrations as low as 0.2 mumol/L in amniotic fluid. Amniotic fluid (1.5 mL)
      is centrifuged at 10,000g for 20 min to obtain a lamellar body pellet, which is
      reconstituted with 0.5 mL of buffer. The PG is measured by a two-step enzymatic
      scheme. Recovery studies demonstrated that the pellet contains > 97% of the PG
      present in amniotic fluid. Between-run CVs were 28%, 5.7%, and 2.6% for amniotic
      fluid controls with means of 0.32, 3.9, and 10.7 mumol/L, respectively (n = 20).
      The enzymatic procedure was not significantly affected by blood, meconium,
      bilirubin, or other phospholipids. Lecithin/sphingomyelin ratio (n = 101) and
      fluorescence polarization (n = 127) compared with log(PG) showed correlation
      coefficients of 0.832 and -0.866, respectively. This test's ability to detect low
      concentrations of PG in amniotic fluid may make it a better predictor of fetal
      lung immaturity than previous methods.

PMID- 8149605
TI  - Early detection of metabolic abnormalities in preterm infants impaired by
      disorders of blood glucose concentrations.
AB  - We recently reported (Acta Paediatr Scand 1992;8: 580-4) three preterm infants
      with severe respiratory distress syndrome and abnormal glucose profiles for the
      first 5 days of life who subsequently died in infancy; only at autopsy were they
      shown to have abnormal glucose-6-phosphatase activity. We have therefore studied
      retrospectively in a matched cohort of 109 infants the blood glucose profiles
      correlated with the severity of respiratory distress syndrome (expressed as the
      fraction of inspired oxygen, FiO2): group A, mild, FiO2 < 0.25; group B,
      moderate, FiO2 0.26-0.50; group C, severe, FiO2 > 0.51. All groups had a similar
      frequency of low blood glucose values (15% < or = 2.2 mmol/L; 29% < or = 2.6
      mmol/L), but high blood glucose values and greater variability in glucose values
      were more common in groups B and C despite lower caloric intakes (A, 4.3%; B,
      9.3%; C, 9.6% > or = 7 mmol/L). We conclude that the early blood glucose patterns
      in those three previously described preterm infants with abnormal hepatic glucose
      6-phosphatase activity at autopsy cannot be viewed as abnormal when considered
      against a matched cohort of infants. Preterm infants at risk of genetic or
      developmental delays in blood glucose homeostasis should be reassessed after
      recovery from their acute illnesses.

PMID- 8149606
TI  - Chemiluminescence receptor assay for measuring vitamin B12 in serum evaluated.
AB  - We evaluated a chemiluminescence receptor assay for vitamin B12 in serum (Magic
      Lite; Ciba Corning Diagnostics), in which an acridinium ester label is used with
      magnetic particle separation. Within- and between-batch precisions were generally
      acceptable, except at low analyte concentrations. The reference range determined
      from 104 elective preoperative patients was 120-610 pmol/L, compared with 150-590
      pmol/L for our in-house radioligand-binding assay. Magic Lite discriminated
      between normal and abnormal results as effectively as the in-house method when
      local reference ranges were applied. Magic Lite demonstrated a negative bias at
      low analyte concentrations and was unable to detect any vitamin B12 in two B12
      deficient patients. Assay accuracy--judged from analytical recovery and
      comparisons with the in-house method and two other radioassay kits (Quantaphase,
      Bio-Rad Labs., and Immophase, Ciba Corning Diagnostics)--was poor at low B12
      concentrations when the manufacturer's recommended two-point calibration was
      used. This problem was partially corrected by using a full set of calibrators.

PMID- 8149607
TI  - Diagnostic power of lecithin/sphingomyelin ratio and fluorescence polarization
      assays for respiratory distress syndrome compared by relative operating
      characteristic curves.
AB  - Amniotic fluids from 328 patients were analyzed for lecithin/sphingomyelin (L/S)
      ratio and surfactant/albumin (S/A) ratio by fluorescence polarization. Of this
      group, 61 neonates showed respiratory distress syndrome (RDS) on delivery within
      3 days of testing. We compared the power of the L/S and S/A in diagnosing
      pulmonary maturity, using relative operating characteristic (ROC) curves. The
      area defined by the ROC curve of the S/A test exceeded the area defined by the
      L/S curve, but this difference was not statistically significant. The diagnostic
      power of the S/A test appears to be at least equal to that of the standard L/S
      test. A review of five cases of RDS in which laboratory tests had suggested
      maturity showed that neither the L/S nor the S/A could satisfactorily resolve the
      problem of false interpretations of maturity, particularly in mothers with
      diabetes mellitus who underwent cesarean section.

PMID- 8149608
TI  - When is a serum iron really a serum iron? The status of serum iron measurements.
AB  - Although serum iron determinations play an important role in the diagnostic
      process, the accuracy of routine methods is suspect. The poor performance of
      currently used methods is well documented in the quarterly College of American
      Pathologists survey reports. Compared with the 1990 method of the International
      Committee for Standardization in Haematology (ICSH), the 1978 ICSH Reference
      Method shows a +3.4% bias and the standard method of the National Committee for
      Clinical Laboratory Standards shows a -17.8% bias for iron results. All routine
      methods checked--DuPont aca, Abbott TDx, Kodak Ektachem (except one lot),
      BM/Hitachi 717, and Synermed--show a negative bias over the entire analytical
      range, a significant negative intercept, and extremely poor correlation with the
      1990 ICSH method for iron values < 750 micrograms/L. Individual discrepancies of
      several hundred percent were observed. Imprecision of the methods is not the
      reason for these discrepancies. We question whether most routine methods
      measuring low iron concentrations provide results sufficiently reliable for
      confirmation of iron deficiency.

PMID- 8149609
TI  - Plasma homocyst(e)ine as a risk factor for early familial coronary artery
      disease.
AB  - We measured plasma homocyst(e)ine [H(e)] and other coronary risk factors in 266
      patients with early coronary artery disease from 170 families in which two or
      more siblings were affected and in 168 unmatched controls. The mean H(e)
      concentration adjusted for significant correlates (serum creatinine, uric acid,
      and low-density lipoprotein cholesterol) was 12.0 mumol/L in proband cases
      compared with 10.1 mumol/L in controls (P = 0.0001). Many (17.6%) of the proband
      cases had H(e) concentrations exceeding the 95th percentile for the controls
      (relative odds = 4.9, P < 0.001). H(e) among cases was bimodally distributed even
      after adjustment for concentrations of plasma vitamins. Concordant high H(e) was
      seen in at least 10 (12%) of 85 families with two or more affected siblings. We
      conclude that a substantial proportion of early familial coronary artery disease
      is probably related to production of high concentrations of H(e) by one or more
      major genes.

PMID- 8149610
TI  - Replacing creatinine measurements with specific gravity values to adjust urine
      cotinine concentrations.
AB  - Creatinine and specific gravity (relative density) measurements both allow
      differences in urine concentration to be taken into account in determining urine
      cotinine concentrations. In this study we demonstrate that the variance of urine
      cotinine measurements is reduced comparably when either creatinine or specific
      gravity measurements are used for correction. This reduction in variability
      improves the correlation between urine cotinine measurements and clinical
      endpoints. In this study, the clinical endpoints were pulmonary function in a
      population of nonsmoking children with asthma, 42% of whom were reported to have
      been exposed to environmental tobacco smoke. When corrected by either creatinine
      measurements or specific gravity values, the urine cotinine measurements
      performed as well or better than reported exposure (and comparably with each
      other) in assessments of lung function. A dose-response relationship was also
      more consistently apparent. Specific gravity values can be used reliably in place
      of creatinine values to adjust urine cotinine measurements for both research and
      clinical purposes.

PMID- 8149611
TI  - Interference in ionized calcium measurements by heparin salts.
AB  - We determined the suitability of various heparin salts used for anticoagulation
      of whole-blood specimens for measurement of ionized calcium (iCa), blood gases,
      and electrolytes. We were particularly interested in a new heparin product
      containing both zinc and lithium cations (CNLZ heparin), in which the binding
      sites with greatest affinity for divalent cations are bound with zinc and low
      affinity sites with lithium. In initial experiments Li heparin decreased iCa
      concentrations 0.07 mmol/L at the lowest heparin concentration (3000 units/L) and
      progressively lowered them at higher concentrations. Zn heparin initially
      increased iCa concentrations 0.06 mmol/L but progressively lowered them as the
      heparin concentration was increased. Li heparin interfered even when present in
      amounts (9 units per 3-mL syringe) minimally effective in preventing coagulation.
      Use of CNLZ heparin (36 units per 3-mL syringe; Zn 63-78 g/kg of heparin) largely
      eliminated interference of heparin in iCa measurements. In studies that included
      the effects of concentration of heparin through partial filling of syringes,
      specimens anticoagulated with CNLZ heparin compared well with unheparinized
      controls in measurements of iCa, blood gases, and electrolytes. Blood gases and
      iCa results on CNLZ-heparinized specimens from intensive-care-unit patients also
      compared well with specimens anticoagulated with a preparation of heparin (EB
      heparin) in which calcium has been added to balance the calcium-binding capacity.
      However, the presence of calcium in EB heparin significantly increased measured
      total calcium concentrations, whereas the new CNLZ heparin did not interfere in
      total calcium determinations.

PMID- 8149612
TI  - Effect of serum lipoprotein(a) on estimation of low-density lipoprotein
      cholesterol by the Friedewald formula.
AB  - The calculation of serum low-density lipoprotein cholesterol (LDL-C) by the
      Friedewald formula does not account for the cholesterol associated with
      lipoprotein(a) [Lp(a)]. To quantify the contribution of Lp(a) cholesterol to
      total serum cholesterol, we measured concentrations of serum Lp(a) by an ELISA
      and concentrations of other serum lipids and lipoproteins by standard assays in
      23 normolipemic women, ages 50-60 years. In measuring serum high-density
      lipoprotein we found that polyethylene glycol 6000 precipitated > 99.8% of all
      Lp(a). When serum Lp(a) concentrations were < or = 300 mg/L, 301-600 mg/L, and >
      600 mg/L, the uncorrected serum LDL-C was overestimated, respectively, by a mean
      of 4.1% (n = 7), 8.5% (n = 8), and 21.4% (n = 8). Serum Lp(a) concentrations were
      positively correlated with percentage overestimation (P < 0.001), but were not
      correlated with either corrected or uncorrected serum LDL-C. We conclude that the
      Friedewald formula should be modified to take into account the contribution of
      Lp(a) cholesterol to total serum cholesterol.

PMID- 8149613
TI  - Biological variability of cholesterol, triglyceride, low- and high-density
      lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B.
AB  - Biological variability is a major contributor to the inaccuracy of cardiovascular
      risk assessments based on measurement of lipids, lipoproteins, or
      apolipoproteins. We obtained estimates of biological variation (CVb) for 20
      healthy adults and calculated the percentiles of CVb as an expression of the
      variability of CVb among individuals for cholesterol, triglyceride, high-density
      lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol,
      apolipoprotein (apo) A-I, apo B, and lipoprotein(a) [Lp(a)] by four biweekly
      measurements of these analytes. The CVb for the group was approximately 6-7% for
      cholesterol, HDL cholesterol, apo A-I, and apo B; approximately 9% for LDL
      cholesterol; and 28% for triglyceride. However, for each analyte, there was a
      considerable variation of CVb among individuals. For all analytes except Lp(a),
      there was no relation between the individual's CVb and the analyte concentration.
      Lp(a) was inversely related to CVb, and there was a very wide variation in the
      CVb for Lp(a) among the participants, ranging from 1% to 51%. The number of
      independent analyses to perform to accurately assess an individual's risk for
      coronary artery disease should be determined on the basis of the individual CVb
      for a given analyte rather than the average CVb.

PMID- 8149614
TI  - Eight compact analysis systems evaluated for measuring total cholesterol.
AB  - We examined the analytical performance of eight compact systems for measuring
      total cholesterol: AccuMeter, Cobas Ready, Discovery f2, DT60, L-D-X, Reflotron,
      QCA, and Vision. We determined average bias at two decision levels, the mean
      absolute bias, and the percentage of results differing from the comparison method
      results by > 8.9% allowable total error limit for multiple reagent lots. Average
      bias was < 3% for all lots tested for AccuMeter, Discovery f2, and DT60, but > 3%
      for one or more lots or sample types tested with the other systems. Of results
      from each reagent lot, > 95% were within the 8.9% total error specifications with
      Discovery f2, DT60, and QCA, whereas the performance of L-D-X, Vision, and
      Reflotron depended on reagent lot and (or) sample type. Of all results from each
      lot tested with AccuMeter and Cobas Ready, > 5% exceeded the total allowable
      error limit. We determined imprecision for five systems: Cobas Ready, Discovery
      f2, and QCA had CVs < 3%, whereas CVs for AccuMeter and L-D-X were > 3% but < 5%.

PMID- 8149615
TI  - International Federation of Clinical Chemistry standardization project for
      measurements of apolipoproteins A-I and B. IV. Comparability of apolipoprotein B
      values by use of International Reference Material.
AB  - We performed temporal and thermal stability studies on SP3-07, a liquid
      stabilized reference material for apolipoprotein (apo) B, selected during the
      previous phase of the International Federation of Clinical Chemistry project on
      standardization of apolipoprotein measurements. Results indicate that SP3-07
      stored at -70 degrees C has the long-term stability required for a reference
      material. We assigned an accuracy-based apo B value of 1.22 g/L to SP3-07, using
      a nephelometric method that was calibrated with freshly isolated low-density
      lipoprotein for which the apo B mass value was determined by a standardized
      sodium dodecyl sulfate-Lowry procedure. Using a common protocol, the study
      participants transferred the assigned mass value from SP3-07 to the individual
      calibrators of the analytical systems and measured the apo B concentration of 20
      fresh-frozen samples obtained from individual donors and covering a clinically
      relevant range of apo B values. The among-laboratory CV on these samples,
      analyzed by 25 analytical systems, ranged from 3.1% to 6.7%. These results
      demonstrate the lack of matrix effects of SP3-07 and its ability to provide
      accurate and comparable apo B values in a variety of immunochemical methods. On
      the basis of the outcome of these studies, the World Health Organization has
      endorsed SP3-07 as the International Reference Material for Apolipoprotein B.

PMID- 8149616
TI  - Citrate as the main small molecule binding Al3+ in serum.
AB  - A recent proposal (Clin Chem 1992;38:1809-18) that inorganic phosphate is the
      predominant small molecule binding Al3+ in blood serum is shown to be incorrect.
      Experiments in which Al3+ is added to solutions containing phosphate and citrate
      in the same proportions as in serum clearly show that citrate prevents formation
      of any aluminum phosphate precipitate, and analysis of these data indicates that
      the assumed binding constants for soluble phosphate are two orders of magnitude
      too strong. Consideration of the effect of competitive binding of alkaline earth
      metal ions to citrate on Al3+ binding and of a set of transferrin-Al3+ stability
      constants leads to the conclusion that the proportions are in close agreement
      with previously published results. We conclude on the basis of stability
      constants that, of the Al3+ in blood serum, approximately 89% (+/- 5%) binds to
      transferrin and approximately 11% (+/- 5%) to citrate.

PMID- 8149617
TI  - Simultaneous determination of mercury speciation in biological materials by
      GC/CVAFS after ethylation and room-temperature precollection.
AB  - We developed a method for the simultaneous determination of monomethyl mercury
      (MMHg), inorganic mercury [Hg(II)], and total mercury (THg) in biological
      materials. A variety of biological materials can be digested in methanolic KOH
      solution. The MMHg and Hg(II) present are converted to volatile ethyl
      derivatives, methylethyl mercury and diethyl mercury, by an aqueous-phase
      ethylation reaction with sodium tetraethylborate. The ethyl derivatives are
      precollected onto a trapping column at room temperature, in case of disconnection
      with the separation/detection system, and then thermally desorbed into a packed
      isothermal gas chromatography (GC) column. Eluted organo-Hg compounds from the GC
      column are decomposed into Hg0, and detection is completed by cold vapor atomic
      fluorescence spectrometry (CVAFS). Pure standard solutions can be used for
      calibration. The sum of MMHg and Hg(II) obtained by this method equals the THg
      value obtained by digestion with HNO3 and H2SO4, reduction with SnCl2, and single
      stage amalgamation/CVAFS for all biological materials studied. Absolute detection
      limits are 0.6 pg and 1.3 pg of Hg as MMHg and Hg(II), respectively,
      corresponding to 0.3 ng and 0.6 ng/g (wet) of sample.

PMID- 8149618
TI  - Decreased signal in Emit assays of drugs of abuse in urine after ingestion of
      aspirin: potential for false-negative results.
AB  - During routine drug analysis with the Syva d.a.u. Emit immunoassays we observed a
      high frequency of urines with lower rates of changes in absorbance (delta A R)
      than the rate for a drug-free urine calibrator. Many of these urines contained
      salicylates. Among 40 urines with apparent salicylate concentrations between 15
      and 420 mg/dL tested for benzoylecgonine (BE), 20 had delta A R < -4 (range +2 to
      -28 mA/min). The rates decreased with increasing salicylate: delta A R = -0.057 x
      (salicylate, mg/dL) -0.22 mA/min (r = 0.85, n = 40, P < 0.01). Urines from 100
      control subjects (no salicylate) had mean +/- SD delta A R values of -1.05 +/-
      2.2 mA/min (range +3 to -7; only two were < -4 mA/min). Although direct addition
      of salicylic acid (200 mg/dL) to urine specimens did not reproduce the negative
      bias, ingestion of aspirin (acetylsalicylic acid) did by -0.09 mA/min per 1 mg/dL
      (72.4 mumol/L) salicylate. Negative biases observed for other Emit d.a.u. assays
      after salicylate ingestion lead us to conclude that ingestion of therapeutic
      doses of aspirin may cause false-negative results for drug screens in urines by
      this technology.

PMID- 8149619
TI  - Steady-state concentration of cyclosporin G (OG37-325) and its metabolites in
      renal transplant recipients.
AB  - The steady-state concentrations of cyclosporin G (OG37-325) (CsG) and six of its
      metabolites (GM1, GM9, GM4N, GM1c, GM1c9, GM19) were measured throughout the 12-h
      dosing interval in six renal transplant recipients receiving CsG as prophylaxis
      against acute cellular rejection. The mean 12-h whole-blood trough concentrations
      (micrograms/L) were CsG, 131 +/- 26; GM1, 79 +/- 55; GM9, 110 +/- 114; GM4N, 28
      +/- 18; GM1c, 31 +/- 18; GM1c9, 216 +/- 145; and GM19, 303 +/- 217. The relative
      concentration of the primary metabolites (GM1, GM9, GM4N) remained stable with
      respect to CsG throughout the dosing interval, whereas that of the secondary
      metabolites increased. The secondary metabolites GM19 and GM1c9 exhibited
      extensive between-patient variation. We investigated the effect of these
      metabolites on commercially available monoclonal antibody-based fluorescence
      polarization immunoassays (FPIA) and RIAs adapted for measurement of CsG. The 12
      h whole-blood trough concentrations measured by FPIA and RIA exceed those
      measured by HPLC by 19% and 36%, respectively. These measured biases corresponded
      closely with the calculated biases (FPIA 19%, RIA 28%) based on the known cross
      reactivities of CsG metabolites and their concentrations. These results suggest
      that cross-reactivity with metabolites account for a large part of the bias
      observed in immunoassays of CsG.

PMID- 8149620
TI  - Human urinary arsenic excretion after one-time ingestion of seaweed, crab, and
      shrimp.
AB  - We studied chemical speciation of arsenic compounds in urine samples by using
      HPLC with inductively coupled plasma mass spectrometry detection. We examined
      urinary arsenic excretion patterns and the arsenic species excreted from nine
      human subjects who ingested seaweed products and crab (or shrimp). Fast urinary
      excretion of unchanged arsenobetaine was seen after ingestion of crab and shrimp,
      which contain arsenobetaine as the major arsenic species. In contrast, the
      arsenosugars, which comprise the major arsenic species in seaweed, are
      metabolized and have a longer retention time in the human body. When nine
      volunteers ingested the commercial seaweed product nori, both the urinary arsenic
      excretion pattern and the excreted arsenic species varied from individual to
      individual, and as many as six metabolites could be detected. It seems that
      arsenosugars are not decomposed by stomach acid and that reactions involving
      enzymatic and (or) microbial activity in the human body may be responsible for
      the metabolism of arsenosugars.

PMID- 8149621
TI  - Automated latex agglutination immunoassay of serum ferritin with a centrifugal
      analyzer.
AB  - A considerable demand for convenient, rapid, inexpensive assays of ferritin in
      serum has been generated in recent years in hospital laboratories and blood
      banks. We describe a simple and rapid particle-enhanced turbidimetric immunoassay
      suitable for routine application in a Monarch 2000 centrifugal analyzer with
      commercially available reagents. This fully automated assay (y) requires no
      pretreatment of sample, and correlation with a two-step sandwich ELISA (x) is
      excellent (y = 1.018x + 0.397, Sy/x = 0.027). The analytical range extends from 5
      to 900 micrograms/L. Intraassay imprecision (CV) ranged from 1.1% to 5% for
      various specimen concentrations. Interassay imprecision ranged from 2.2% for
      above-normal concentrations (755 micrograms/L) to 9.5% for low concentrations (39
      micrograms/L). No specimen-related carryover was detected. The method has been
      useful in our predeposit autologous blood transfusion program for rapid
      assessment of iron status in patients undergoing repeated phlebotomies.

PMID- 8149622
TI  - Modified immunoselection technique for definitive diagnosis of heavy-chain
      disease.

PMID- 8149623
TI  - Bias of ionized calcium results from blood gas syringes.

PMID- 8149624
TI  - Analytical quality specifications in clinical chemistry.

PMID- 8149625
TI  - Selectivity of enzymatic assays of sodium and potassium.

PMID- 8149626
TI  - Stabilization of human brain natriuretic peptide in blood samples.

PMID- 8149627
TI  - Diagnostic value of a single measurement of troponin T in serum for suspected
      acute myocardial infarction.

PMID- 8149628
TI  - An investigation of argininosuccinic acid anhydrides in argininosuccinic acid
      lyase deficiency by 1H-NMR spectroscopy.
AB  - Argininosuccinate (ASA) is excreted in large amounts in the urine of patients
      with argininosuccinate lyase (EC 4.3.2.1) deficiency (ASLD). Previous workers
      have reported the presence of anhydrides of ASA in the urine of patients with
      this disorder. We have used 1H-NMR spectroscopy to investigate the presence of
      these compounds in untreated urine. Our results indicate that the anhydrides were
      absent from urine and are artifacts produced by the conditions prevailing in the
      methods of analysis previously used to investigate the urine from patients with
      ASLD. We have also attempted to reproduce the conditions that might promote the
      transition to the anhydrides in the urine from a patient with ASLD and in
      solutions of argininosuccinate. Resolution of ASA and the two anhydrides is
      possible and a spectrum of the urine from a patient with ASLD shows that the
      anhydrides are present at below 1% of the total ASA under normal physiological
      conditions.

PMID- 8149629
TI  - A novel HPLC method for the simultaneous quantification of monosaccharides and
      disaccharides used in tests of intestinal function and permeability.
AB  - The quantification of monosaccharides and disaccharides used as probes in
      intestinal function and permeability tests can be technically demanding,
      detracting from the value of this approach to the indirect assessment of
      intestinal damage. In this study, a procedure is described for the simultaneous
      quantification of rhamnose, lactulose, 3-O-methyl-D-glucose and xylose in urine
      by HPLC using an anion exchange column with pulsed amperometric detection. This
      method is relatively fast and simple to perform, requiring no pre-treatment of
      urine samples or post-column derivatization. Accuracy and precision of
      determinations are illustrated by analytical recoveries (mean percentage +/-
      S.D., CV., n = 30) for multiple batch analyses of a diluted urine sample
      containing 20 mg/l of rhamnose (100 +/- 6.8, 6.2%), lactulose (100 +/- 6.1,
      5.5%), 3-O-methyl-D-glucose (98 +/- 5.9, 5.5%) and xylose (104 +/- 7.1, 6.5%).
      Linearity of standard curves indicated that the lower limit for accurate
      quantification was 0.1 mg/l for all four sugars. Urinary recoveries following
      oral administration of these sugars to control dogs were determined as a baseline
      for the investigation of intestinal damage in this species and comparison of
      chromatograms illustrated enhanced permeability in dogs with gluten-sensitive
      enteropathy.

PMID- 8149630
TI  - LDL sialic acid content in patients with coronary artery disease.
AB  - Low density lipoproteins (LDL) are considered to be the most atherogenic of
      lipoproteins. These LDL can be modified and oxidative modifications are now well
      known. In addition, other atherogenic modifications of LDL exist, such as
      desialylation. In the present study sialic acid content was determined in LDL
      preparations obtained from patients with coronary artery disease (CAD+) and
      compared with that of healthy subjects and patients without coronary heart
      disease (CAD-). The sialic acid concentration was found to be statistically lower
      (P < 0.05) in the LDL of CAD+ patients (11.6 +/- 2.7 micrograms/mg of protein)
      than in the LDL of controls (16.5 +/- 5.6 micrograms/mg of protein) or in the LDL
      of CAD- patients (15.3 +/- 3.8 micrograms/mg of protein). In subgroups of CAD+
      patients divided according to the severity of the disease, no statistically
      significant difference was observed in LDL sialic acid content. This work
      confirms the presence of desialylated LDL in the sera of patients with atheroma.

PMID- 8149631
TI  - The investigation of UDPGlucose and UDPGalactose concentration in red blood cells
      of patients with classical galactosaemia.
AB  - UDPGlucose (UDPGlc) and UDPGalactose (UDPGal) are nucleotide sugars formed via
      the galactose metabolic pathway and are essential cofactors for the incorporation
      of galactose and glucose into complex glycoproteins and glycolipids. It has been
      proposed that in classical galactosaemia, where the enzyme galactose-1-phosphate
      uridyl transferase is deficient, the reaction product UDPGal is reduced leading
      to the long-term complications associated with the disease. We have measured the
      concentration of UDPGal and UDPGlc in red blood cells by high performance liquid
      chromatography (HPLC) in 16 children and 15 adult galactosaemics and compared the
      results with 30 and 27 control children and adults, respectively. The results
      indicate that UDPGal levels were found to be significantly reduced in
      galactosaemic patients and UDPGlc/UDPGal ratios significantly increased.

PMID- 8149632
TI  - Is an increase of deoxyribonucleases activity in uraemic lymphocytes caused by
      their augmented synthesis in these cells?
AB  - Deoxyribonucleases activity in T and B lymphocytes isolated from 45 patients with
      chronic renal failure and 30 control subjects was measured. The results obtained
      clearly show a dramatic increase in enzyme activity in both T and B lymphocyte
      cells isolated from uraemic patients when compared with the control cell. The
      increase in enzyme activity was limited to the group of relatively small
      nucleases ranging from 14 kDa to 18 kDa. Since it was shown previously that these
      nucleases are among the cleavage products of the largest subunit of DNA-dependent
      RNA polymerase class I, it is suggested that a characteristic feature of the
      lymphocyte cell isolated from uraemic patients is increase of RNA polymerase
      lability, thus resulting in RNA synthesis decrease. Amongst toxins increasing
      catabolism of the active polymerase enzyme, a significant correlation with the
      vise of lymphocyte Mg2+ and Mn2+ ions was disclosed.

PMID- 8149633
TI  - Characterization of apo(a) polymorphism by a modified immunoblotting technique in
      an Italian population sample.
AB  - Apo(a), the specific lipoprotein(a) (Lp(a)) apolipoprotein, is characterized by
      different isoforms (from 6 to 11 on SDS-PAGE) encoded by a system of autosomal
      codominant alleles. Electrophoresis on agarose gel displays a better resolving
      power than SDS-PAGE (a larger number of apo(a) isoforms is detected). The aim of
      this work was to set up a simple technique that uses a capillary blotting
      apparatus and a polyvinylidene difluoride membrane for protein transfer. We
      tested an Italian population sample of 202 healthy subjects (123 men and 79
      women) and we detected 22 apo(a) isoforms varying from 280 to 775 kDa. In our
      sample, 135 subjects (66.5%) had a single-band phenotype, 64 (31.7%) had a double
      band phenotype and 3 subjects (1.5%) had no detectable bands ('null' phenotype).
      This simple and reproducible technique could be applied in the genetic screening
      of apo(a) polymorphisms and for clinical investigations of the risk of developing
      cardiovascular diseases.

PMID- 8149634
TI  - Diagnosis of mucopolysaccharidoses in a clinically selected population by urinary
      glycosaminoglycan analysis: a study of 2,000 urine samples.
AB  - Two thousand urine samples (from patients presenting with clinical features
      suggestive of a mucopolysaccharidosis, MPS) were analysed by a procedure that
      included a quantitative measurement of glycosaminoglycan (GAG) hexuronic acids
      (harmine reagent), a qualitative GAG analysis (cellulose acetate electrophoresis)
      and a study of urinary oligosaccharide patterns. One hundred and seventy MPS and
      29 oligosaccharidosis-affected patients were found, but 23 MPS patients among the
      170 would have been missed by use of a quantitative procedure only. Fourteen of
      these (mainly MPS IV A) were detected on the basis of abnormal electrophoresis
      and the 9 others on the basis of abnormal urinary oligosaccharide patterns (MPS
      IV B patients). Our results emphasize that normal quantitative GAG excretion
      alone cannot rule out a diagnosis of MPS; qualitative analysis is also required,
      as well as oligosaccharide screening.

PMID- 8149635
TI  - Serum bile acid concentrations in mild liver cirrhosis.
AB  - Fasting serum conjugated bile salt concentrations were measured in a group of 20
      patients with moderate post-hepatitis cirrhosis. Twenty healthy volunteers were
      used as controls. The individual conjugated bile acids were analyzed by a
      specific and sensitive method which couples reversed-phase high-performance
      liquid chromatography with mass spectrometry. Significantly elevated levels of
      the total and individual conjugated bile acids were found in cirrhotic patients.
      The predominant serum bile acids were conjugates of chenodeoxycholic acid. The
      conjugates of lithocholic acid were also increased; in subjects with normal liver
      function, on the contrary, they were found only in traces.

PMID- 8149636
TI  - An increase of serum remnant-like particles in non-insulin-dependent diabetic
      patients with microalbuminuria.

PMID- 8149637
TI  - Study of chronic granulomatous disease by a nitroblue tetrazolium densitometric
      kinetic test: a new research method.

PMID- 8149638
TI  - Beta-N-acetylhexosaminidase in spinal muscular atrophy fibroblasts.

PMID- 8149639
TI  - The validity of the ethanol precipitation method for the measurement of mucin
      content in human gastric juices and its possible relationship to gastroduodenal
      diseases.

PMID- 8149640
TI  - Microwave oven digestion procedure for atomic absorption spectrometry analysis of
      bone and teeth.
AB  - The purpose of this study was to develop a new method for determination of the
      mineral element in teeth and bone using a microwave digestion procedure coupled
      to atomic absorption spectrometry. Samples were ashed at 450 degrees C for 4.5 h
      and subsequently digested in a microwave oven at maximum power (600 W) for 10 s
      using a Teflon closed Parr bomb. This method permits the rapid dissolution of the
      biological samples, avoiding operations such as slicing and cutting which often
      introduce alterations in sample homogeneity and may contribute to their
      contamination. The analysis of Na, K, Ca, Mg, Fe, Zn, Ba, Cd and Pb showed good
      reproducibility, precision and accuracy as compared with the certified values for
      the IAEA H-5 animal bone. Average concentration for those elements in permanent
      teeth obtained from children aged 11-18 years by orthodontics are given.

PMID- 8149641
TI  - Insulin receptor binding to erythrocytes in the first half of pregnancy is
      increased in healthy pregnant women as compared with non-pregnant or gestational
      diabetic women.
AB  - Insulin binding to erythrocytes was measured longitudinally by a competitive
      radioreceptor assay in 21 healthy pregnant (HP) and 20 well-controlled
      gestational diabetic women (GD) in 4-week intervals throughout pregnancy and at
      day 4 post-partum. Maximum insulin binding (maxbdg) at weeks 8-14 was increased
      (P < 0.001) in HP (median: 6.0%) but not in GD (median: 2.7%) as compared with
      non-pregnant control subjects (C) (median: 3.6%; previously reported: Clin. Chim.
      Acta 1992;207:57-71) due to an increased number of high-affinity insulin
      receptors. Throughout gestation the binding decreased continuously, to reach at
      term the levels found in C. In GD maxbdg remained close to the level of C
      throughout pregnancy. Binding differences between HP and GD were independent of
      the body mass index. Maxbdg did not differ between diet- and insulin-treated
      patients. It was higher in women whose offspring had low umbilical cord insulin
      levels (< 10 mu units/ml). The findings suggest that (a) higher insulin binding
      in HP could contribute to the improved glucose tolerance in early pregnancy and
      (b) the lack of increase in insulin binding during early pregnancy in gestational
      diabetes might be one factor leading to the manifestation of the disease in late
      pregnancy. However, it must be kept in mind that insulin receptors on
      erythrocytes do not necessarily resemble those on the major target tissues of
      insulin.

PMID- 8149642
TI  - The lysosomal N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes in plasma: study
      of distribution in a general population by a simple routine chromatofocusing
      procedure.
AB  - We have adapted for routine analysis a pre-existing method for separating the
      three major N-acetyl-beta-D-glucosaminidase (NAG) isoenzyme forms--A, B+I1 and I2
      -by chromatofocusing followed by fluorimetric assay of the enzyme activity. This
      method combines good resolution, accurate quantification of the different
      isoenzymes and high reproducibility with an acceptable degree of analytical
      precision. We have applied it to studying the isoenzyme levels in the plasma of a
      general population of 417 subjects and have analysed these enzyme activities as
      functions of age, sex, body mass and declared alcohol consumption. Unlike the
      levels of unfractionated enzyme, levels of all the isoenzymes were higher in men
      than in women at all ages except in the 20-29 year group. Isoenzyme I2 showed the
      greatest sex difference. On the whole, with increasing age, both sexes showed
      more or less regular increases in plasma levels of all the isoenzymes. We also
      found significant correlations for the population as a whole with age and with
      body mass index. The only significant correlation with alcohol consumption was
      for B+I1 in men.

PMID- 8149643
TI  - Changes in the glycoforms of rat alpha-1-acid glycoprotein during experimental
      polyarthritis.
AB  - We analyzed the carbohydrate moiety of purified alpha-1-acid glycoprotein (AGP)
      from Lewis adult male rats that were healthy (AGPh) or had experimental
      polyarthritis (AGPi). Sodium dodecyl sulfate polyacrylamide gel electrophoresis
      before and after N-glycanase treatment showed that AGPi had a slightly lower
      molecular mass (43 kDa vs. 45 kDa for AGPh) due to a lesser carbohydrate content.
      Carbohydrate analysis of purified AGP showed a slight decrease in the sialyl and
      galactosyl molar ratio in polyarthritis. However, the same difference in AGPh and
      AGPi (i.e. 0.6 residue) between the sialyl and galactosyl molar ratio indicated
      more than one sialyl residue per complex-type branch. Affinity for concanavalin A
      (ConA) of the whole glycoprotein and released oligosaccharides showed a
      progression during polyarthritis towards more reactive glycoforms or more ConA
      bound oligosaccharides. Anion-exchange HPLC of the ConA-fractionated
      oligosaccharides corroborated the decreased sialylation in polyarthritis. Taken
      together, these results suggest a fall in branched and sialylated
      oligosaccharides during experimental polyarthritis. These structural changes
      might be related to an increase in Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase
      activity described elsewhere in inflammatory states.

PMID- 8149644
TI  - Cholesteryl ester transfer activity in lipoprotein lipase deficiency and other
      primary hypertriglyceridemias.
AB  - Cholesteryl ester transfer protein (CETP) activity was measured in d > 1.21 g/ml
      plasma from hypertriglyceridemic patients and compared with normolipidemic
      subjects. The assay consisted in measuring the specific transfer of
      [3H]cholesteryl oleate from a prelabelled, apo E-poor HDL fraction to VLDL after
      incubation at 37 degrees C in the presence of the d > 1.21 g/ml plasma sample:
      the lipoproteins were then separated by precipitation with dextran sulfate/Mg2+
      solution. Increasing the volume of d > 1.21 g/ml plasma or purified human CETP in
      the assay produced linear responses in measured activity, whereas, either during
      incubation at 4 degrees C or in the presence of rat plasma instead of human
      plasma, the transfer of [3H]cholesteryl oleate to VLDL was not stimulated. Thus,
      the assay reflects changes in CETP in the sample and appears to be suitable for
      measuring CETP activity in d > 1.21 g/ml plasma. CETP activity was very similar
      in the two groups of normolipidemic subjects considered: adolescents (203 +/- 11
      nmol esterified cholesterol transferred per 8 h/ml plasma) and adults (215 +/-
      5). Patients were grouped into lipoprotein-lipase (LPL)-deficient and non-LPL
      deficient according to their enzyme activity in postheparin plasma. CETP activity
      was highly increased in LPL-deficient, severe hyperchylomicronemic patients (430
      +/- 42) and was directly correlated with VLDL levels in the non-LPL-deficient
      individuals. Marked differences were observed in the lipid composition of HDL and
      apolipoprotein A-I levels among patients and controls. In the control group, CETP
      activity was correlated only with HDL-triglyceride and HDL-triglyceride/apo A-I
      mass ratio, which is compatible with the physiological role of CETP in
      transferring triglyceride to HDL from other lipoprotein particles. When all
      hypertriglyceridemic patients were considered together, CETP activity was
      inversely correlated with apo A-I and HDL-cholesterol, whereas it was directly
      correlated with HDL-triglyceride/HDL-cholesterol and HDL-triglyceride/apo A-I
      mass ratios. The results indicate that the enhanced CETP activity associated with
      hypertriglyceridemia contributes to the compositional change of HDL, which in
      turn may be responsible for the reduction of HDL levels in this condition.

PMID- 8149645
TI  - A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 2 (72
      kDa gelatinase/type IV collagenase) using monoclonal antibodies.
AB  - A one-step sandwich enzyme immunoassay (EIA) for human matrix metalloproteinase 2
      (MMP-2, 72-kDa gelatinase/type IV collagenase, EC 3.4.24.24) was established with
      a pair of monoclonal antibodies prepared against the precursor form of MMP-2
      (proMMP-2) purified from the conditioned medium of human skin fibroblasts or
      against a synthetic peptide corresponding to the N-terminal domain of proMMP-2.
      ProMMP-2 in samples was allowed to simultaneously react with both solid-phase and
      peroxidase-labeled antibodies. Sensitivity of this EIA system was 2.4 pg/assay
      (0.24 microgram/l) and linearity was obtained between 10 and 5,000 pg/assay (1.0
      500 micrograms/l). The EIA system recognized both the free form of proMMP-2 and
      its complex form with TIMP-2 with the same degree of immunoreactivity. ProMMP-2
      levels in human sera from patients in various disease states were analyzed. In
      sera from patients with hyperthyroidism (12), primary biliary cirrhosis (8) and
      hepatocellular carcinoma (11), 749 +/- 166, 716 +/- 135 and 686 +/- 236
      micrograms/l of proMMP-2 were detected, respectively and these were significantly
      higher than that observed in 213 normal human sera (570 +/- 118 micrograms/l). In
      contrast, the levels in sera from 33 patients with osteoarthritis (449 +/- 72
      micrograms/l), 45 with rheumatoid arthritis (408 +/- 139 micrograms/l), 13 with
      stomach cancer (427 +/- 103 micrograms/l) and 10 with pancreatic cancer (422 +/-
      130 micrograms/l) were significantly lower than that found in normal sera.
      Immunoblot and gel filtration analyses showed that human sera contain several MMP
      2 species in addition to proMMP-2 which exist in a complex form with TIMP-2.

PMID- 8149646
TI  - Prenatal detection of cri du chat syndrome on uncultured amniocytes using
      fluorescence in situ hybridization (FISH).
AB  - Fluorescence in situ hybridization (FISH) with a chromosome-region-specific DNA
      probe was used prospectively on uncultured amniocyte interphase cells to detect
      an unbalanced chromosome abnormality that resulted in cri du chat or 5p-
      syndrome. Confirmation was performed by routine cytogenetics.

PMID- 8149647
TI  - Thyroid cancer in a case with the Alagille syndrome.
AB  - A 19-year-old woman with the Alagille syndrome developed papillary thyroid
      carcinoma with lung metastasis. She was diagnosed as having Alagille syndrome at
      the age of 8. Following total thyroidectomy and lymph nodes dissection, iodine
      131 therapy was conducted for local and distant metastases. This is the first
      report of a case of thyroid cancer accompanying Alagille syndrome.

PMID- 8149648
TI  - Defective G2 repair in Down syndrome: effect of caffeine, adenosine and
      niacinamide in control and X-ray irradiated lymphocytes.
AB  - Lymphocytes from both Down syndrome (DS) patients and age-matched control donors
      have been investigated to identify a possible disturbance in chromosomal G2
      repair. Analyses of caffeine treatments during G2 have shown that the frequency
      of chromosomal aberrations is higher in DS lymphocytes than in normal
      lymphocytes. Likewise, G2 duration is longer in DS cells than in normal cells. In
      both control and DS lymphocytes, caffeine treatments increase the frequencies of
      chromatid breakages and decrease the average of G2 duration. The reversal of the
      caffeine potentiation effect by adenosine and niacinamide is higher in DS cells
      than in normal cells. Furthermore, ATP content per cell in DS lymphocytes is one
      third of that estimated in normal lymphocytes. The increase of ATP level produced
      by adenosine or niacinamide generally correlates with the reversal of the
      caffeine effect on chromosome aberrations. Under the experimental conditions
      tested, a good negative exponential correlation between ATP level and chromosome
      aberrations has been detected in both normal and DS lymphocytes which were or
      were not X-irradiated. Finally, we postulate a decrease in G2 repair capability
      of DS lymphocytes caused by a low availability of ATP and/or some other factor
      correlating with it.

PMID- 8149649
TI  - Occipital horn syndrome: report of a patient and review of the literature.
AB  - We report an 18-year-old boy with occipital horn syndrome and we review the 20
      cases previously published with this syndrome. The distinctive features common to
      all patients were unusual facial appearance, skeletal abnormalities, chronic
      diarrhea and genitourinary abnormalities. The skeletal abnormalities included
      occipital horns, short, broad clavicles, deformed radii, ulnae, and humeri,
      narrowing of the rib cage, undercalcified long bones with thin cortical walls and
      coxa valga. Occipital horn syndrome is inherited in an X-linked recessive
      fashion. Our analysis indicates that occipital horn syndrome is associated with a
      recognizable characteristic phenotype.

PMID- 8149650
TI  - Direct transmission of a tandem duplication in the short arm of chromosome 8.
AB  - A family is described in which a mother and her two children carry a tandem
      duplication of the short arm of chromosome 8. Their phenotypes are similar and
      characterised by distinct facial dysmorphism, small stature and mild mental
      retardation. This is one of the first cases of direct familial transmission of a
      partial duplication of an autosomal chromosome segment.

PMID- 8149651
TI  - Male with type II autosomal recessive cutis laxa.
AB  - A 5-year-old boy, who had pre- and postnatal growth retardation, delayed motor
      development, cutis laxa, delayed closure of large fontanels, congenital hip
      dislocation and characteristic facies, is described. Disorders with cutis laxa
      are now divided into five types. The patient had clinical manifestations very
      similar to those of cutis laxa with bone dystrophy (type II autosomal recessive
      cutis laxa). Eighteen patients have been reported, the ratio of males to females
      being 5 to 14. This is the fifth case of this disorder occurring in a male, which
      provides further evidence for autosomal recessive inheritance.

PMID- 8149652
TI  - Myoclonic epilepsy and a maternally derived deletion of 15pter-->q13.
AB  - Deletion of a 15pter-->q13 segment of maternal origin was observed in a mentally
      retarded infant. In addition to the symptoms common to deletions of proximal 15q,
      the phenotype included myoclonic epilepsy of early infantile onset. The deletion
      was caused by a 3:1 disjunction in the mother, who was a carrier of
      t(15;22)(13q;p11) translocation.

PMID- 8149653
TI  - Exclusion of an elastin gene (ELN) mutation as the cause of pseudoxanthoma
      elasticum (PXE) in one family.
AB  - An intragenic elastin Hinf I polymorphism has been used to study the inheritance
      of elastin alleles in a family considered to show recessive inheritance of
      pseudoxanthoma elasticum (PXE). The marker has proved informative, excluding the
      elastin gene as a cause of PXE in this family. In addition, whole genomic human
      elastin clones were used in Southern analysis to screen the family for gross
      elastin gene rearrangements, but none were detected.

PMID- 8149654
TI  - A constitutional mutation within the retinoblastoma gene detected by PFGE.
AB  - Retinoblastoma may be caused by constitutional mutations in the retinoblastoma
      gene which segregates as an autosomal dominant inherited predisposition for
      developing retinoblastoma tumours. Since 75% of these cases are new mutations,
      there is a need for methods to identify carriers of such germ-line mutations, so
      that informed genetic counselling is available to patients and close relatives.
      We have used pulsed-field gel electrophoresis in screening 20 unrelated cases
      with bilateral retinoblastoma. One constitutional mutation could be detected, and
      was found to be caused by a balanced chromosome (4;13) translocation with the
      breakpoint within intron 17 of the retinoblastoma gene.

PMID- 8149656
TI  - Detection of antibodies to ovarian antigens in women with premature ovarian
      failure.
AB  - Premature ovarian failure is a common condition of uncertain aetiology in most
      cases, although autoimmunity is thought to play a role in a proportion of cases.
      The frequency of ovarian antibodies, which may be markers for an autoimmune
      aetiology in this condition, remains unclear. To define this further, we have
      examined the sera of 45 women with premature ovarian failure (five with
      iatrogenic ovarian failure, nine with an associated autoimmune disease, and 27
      with idiopathic ovarian failure), as well as four women with infertility due to
      Turner's syndrome and 41 pre- and post-menopausal controls. Using two human
      ovarian antigen preparations, 24% and 60% of the ovarian failure patients reacted
      in an ELISA (P < 0.05 and P < 0.001 compared with controls), but frequent cross
      reactivity was found with fallopian tube antigens. The apparent aetiology of
      ovarian failure did not correlate with the presence of ovarian antibodies. Using
      bovine ovary as an antigen, there was a significant overall increase in binding
      by the ovarian failure patients, but this was almost identical to binding in an
      ELISA with bovine fallopian tube. In contrast to a previous report, there was no
      significant increase of binding to soluble or Triton-extracted membrane fractions
      of bovine corpora lutea containing the LH/hCG receptor by the patients with
      ovarian failure. These results suggest that ovarian antibodies are common in
      premature ovarian failure, but their specificity and pathogenic role are
      questionable.

PMID- 8149655
TI  - Cytokines and autoimmunity.
AB  - Although the immunopathology of most autoimmune diseases has been well defined,
      the mechanisms responsible for the breakdown of self-tolerance and which lead to
      the development of systemic and organ-specific autoaggression are still unclear.
      Evidence has accumulated which supports a role for a disregulated production of
      cytokines by leucocytes and possibly other cells in the pathogenesis of some
      autoimmune diseases. However, due to the complexity and heterogeneity of cytokine
      effects in the regulation of the immune response, it is difficult to determine
      whether abnormalities in the patterns of cytokine production are primary or
      secondary to the pathological process. Confusion is also caused by the fact that
      the biological activities of cytokines are multiple and often overlapping, and
      consequently it is difficult to focus on a unique effect of any one cytokine.
      Characterization of the potential and actual involvement of cytokines is
      important not only for a better understanding of the pathogenesis of autoimmune
      conditions, but particularly because of the implications for the development of
      immunotherapeutic strategies for the prevention and treatment of the diseases.

PMID- 8149658
TI  - Generation and characterization of a continuous line of CD8+ suppressively
      regulatory T lymphocytes which down-regulates experimental autoimmune orchitis
      (EAO) in mice.
AB  - We have previously shown that two injections with viable syngeneic testicular
      germ cells (TC) alone developed experimental autoimmune orchitis (EAO) in C3H/He
      mice, and that the induction of antigen-specific tolerance in this EAO model is
      associated with the generation of antigen-specific suppressively regulatory T
      (Ts) cells. For the elucidation of the nature of these Ts cells, a murine Ts cell
      line (designated Ts-A) was established. This line was generated from the spleen
      cells of C3H/He mice which had received three i.v. injections of a soluble
      (deaggregated) form of murine testicular antigen (mTA), followed by the repeated
      selection of these spleen lymphocytes in vitro by stimulation with mTA. Adoptive
      transfer of Ts-A cells into naive syngeneic mice immediately before the first TC
      injection was found to downgrade EAO in actively immunized recipients. The
      transferred Ts-A cells significantly inhibited the cellular immune response to TC
      in the recipients in an antigen-specific manner, but these cells had no
      inhibitory effect on the humoral immune response to TC. This line could also
      inhibit in vitro syngeneic TC-driven proliferation of orchitogenic lymphocytes.
      Surface phenotype of this line was CD8+, CD4-, Thy-1.2+, CD3+, and TCR alpha
      beta+. These findings may suggest an in vivo role for suppressively regulatory
      lymphocytes, capable of inhibiting helper T cells, in the regulation of EAO.

PMID- 8149657
TI  - Absence of autoantibodies against glutamate decarboxylase (GAD) in the non-obese
      diabetic (NOD) mouse and low expression of the enzyme in mouse islets.
AB  - GAD is a major islet cell autoantigen in human type 1 diabetes mellitus.
      Autoantibodies are preferentially directed against the 65-kD isoform of the
      enzyme which is the only form expressed in human islets of Langerhans. The NOD
      mouse is a spontaneous model of type 1 diabetes, frequently employed in studies
      dealing with the immunopathogenesis of the disease. In the present study the
      reactivity of sera from 34 prediabetic and 15 diabetic NOD mice was tested
      against GAD protein present in islets of Langerhans and cerebellum, and against
      recombinant, semi-purified GAD-65 and GAD-67. A rabbit antiserum (K2) raised
      against GAD-67 could readily recognize the recombinant GAD-67 and the isoform
      present in rat and mouse islets and mouse brain. A MoAb (GAD-6) specific for the
      GAD-65 isoform reacted against the recombinant GAD-65 and the isoform present in
      rat islets and mouse brain, whereas no reactivity was observed when using mouse
      islets. However, when testing the NOD mice sera by immunohistochemistry,
      immunoprecipitation and Western blot, no reactivity against any of the isoforms
      of GAD could be detected. Using reverse transcription polymerase chain reaction
      (PCR), GAD-67 mRNA could be detected in mouse and rat islets and in mouse brain.
      GAD-65 mRNA could also be detected in rat islets and mouse brain, but apparently
      a much lower copy number is present in mouse islets. These findings stress
      important differences in the immune response occurring in the animal model NOD
      mouse compared with human type 1 diabetes, and emphasize that human and animal
      type 1 diabetes possibly represent the final outcome of several different
      etiological factors.

PMID- 8149659
TI  - Elevated tumour necrosis factor-alpha (TNF-alpha) biological activity in
      psoriatic skin lesions.
AB  - Lesions of the common inflammatory skin disease psoriasis are characterized by
      epidermal hyperproliferation, leucocyte adhesion molecule expression and
      leucocyte infiltration. The local release of proinflammatory cytokines, such as
      TNF-alpha, may play an important role in the induction of these events. We have,
      therefore, analysed aqueous extracts of lesional and uninvolved (clinically
      normal) stratum corneum for the presence of TNF-alpha immunoreactivity and
      biological activity. TNF-alpha immunoreactivity and bioactivity were consistently
      higher in lesional compared with uninvolved samples. By using an anti-TNF-alpha
      neutralizing antibody it was demonstrated that the biological activity measured
      was due to the presence of TNF-alpha alone. Concentrations of soluble TNF
      receptors (p55 and p75) were also higher in lesional stratum corneum extracts,
      with the p55 form predominating. The plasma of psoriatic patients was also found
      to contain elevated concentrations of soluble p55 compared with normal controls.
      These results confirm the presence of immunoreactive TNF-alpha and, for the first
      time, conclusively demonstrate TNF-alpha biological activity and quantifiable
      concentrations of soluble TNF receptors (p55 and p75) in lesional psoriatic
      samples. TNF-alpha recovery from stratum corneum probably reflects synthesis in
      deeper, viable layers, where it is likely to exert its biological effects. Local
      and systemic release of soluble TNF receptors, in particular p55, may serve to
      regulate the effects of TNF-alpha in psoriasis.

PMID- 8149660
TI  - Role of membrane-associated lymphotoxin (mLT) in the killing activity of
      lymphokine-activated killer (LAK) cells towards various tumour cell lines.
AB  - Human lymphokine-activated killer (LAK) cells developed by an incubation of
      peripheral mononuclear cells with IL-2 express the membrane-associated
      lymphotoxin (LT)-related molecule (mLT). By a further cultivation of mLT
      expressing (mLT-positive) LAK cells for 24 h without IL-2, mLT disappears (mLT
      negative LAK cells). Cytotoxicities of various tumour cell lines by either mLT
      positive or -negative LAK cells were compared. Eight out of 12 tumour cell lines,
      less susceptible to mLT-negative LAK cells than mLT-positive LAK cells, were
      categorized as group A. Two tumour cells (K562 and Molt-4) had the same
      susceptibility to both kinds of LAK cells. The others (Daudi and Jurkat) had less
      susceptibilities only when they were assessed at E:T ratios of less than 5. The
      four tumour cell lines in the latter two cases, containing K562, Molt-4, Daudi
      and Jurkat cells, were categorized as group B. The cytotoxicities of group A
      tumour cells, but not group B tumour cells, by LAK cells were significantly
      suppressed by the presence of anti-LT antibody. Group A tumour cells had higher
      LT-binding ability (2.82-16.44 fmol/10(6) cells) than group B tumour cells (less
      than 1.46 fmol/10(6) cells). Both mLT-positive and -negative LAK cells had
      similar perforin activities and tumour cell-binding capacities. These results
      suggest that the mLT-mediated killing mechanism is involved in tumour cell
      killing by LAK cells. Further, various tumour cell lines can be classified into
      two large groups according to their susceptibilities to the mLT-mediated killing
      by LAK cells.

PMID- 8149661
TI  - Human T cells in hu-PBL-SCID mice proliferate in response to Daudi lymphoma and
      confer anti-tumour immunity.
AB  - In vitro culture of human peripheral blood lymphocytes (PBL) with Daudi (Burkitt
      lymphoma) cells results in selective proliferation of V gamma 9/V delta 2 T cells
      with high cytotoxicity against Daudi cells. After adoptive transfer into severe
      combined immunodeficient (SCID) mice, these cells exert specific anti-tumour
      activity against Daudi lymphoma. To test whether cytotoxic V gamma 9/V delta 2 T
      cells are induced in SCID mice, human PBL injected intraperitoneally were
      stimulated with irradiated Daudi cells (PBL/Daudi-SCID). After 7-14 days,
      PBL/Daudi-SCID had a significantly higher percentage of human gamma delta T cells
      in their peritoneal cavity, lymph nodes and blood than controls (PBL-SCID). DNA
      content analysis of T cell subsets from PBL/Daudi-SCID showed a significantly
      higher percentage of cells in S + G2 + M phases of the cell cycle in the TCR
      gamma delta-1+ than in CD3+ cell population. Human cells recovered from PBL/Daudi
      SCID showed specific cytotoxicity against Daudi cells. PBL/Daudi-SCID inoculated
      with a lethal dose of Daudi lymphoma survived significantly longer than controls.
      This protection was specific for Daudi cells and was not mediated by murine
      natural killer (NK) cells. Thus human peripheral blood T cells grafted in SCID
      mice proliferate in response to antigen and confer specific immunity.

PMID- 8149662
TI  - Differential effect of glucocorticoids on tumour necrosis factor production in
      mice: up-regulation by early pretreatment with dexamethasone.
AB  - Glucocorticoids (GC) are well known inhibitors of tumour necrosis factor (TNF)
      production. We investigated the role of endogenous GC in the regulation of TNF
      production in mice treated with lipopolysaccharide (LPS) using a pretreatment
      with dexamethasone (DEX) to down-regulate the hypothalamus-pituitary-adrenal axis
      (HPA). Short-term DEX pretreatment (up to 12 h before LPS) inhibited TNF
      production, but earlier (24-48 h) pretreatments potentiated it. This up
      regulating effect was not observed in adrenalectomized mice or when GC synthesis
      was inhibited with cyanoketone (CK). This effect could not be explained only by
      the suppression of LPS-induced corticosterone (CS) levels induced by DEX, since a
      48-h pretreatment potentiated TNF production without affecting LPS-induced CS
      levels. On the other hand, mice chronically pretreated with DEX were still
      responsive to its inhibitory effect on TNF production, thus ruling out the
      possibility of a decreased responsiveness to GC.

PMID- 8149663
TI  - The influence of anti-fibronectin antibodies on interactions involving
      extracellular matrix components and cells: a possible pathogenic mechanism.
AB  - Antibodies, directed to the 30-kD collagen binding domain (CBD) of fibronectin
      (Fn), have been previously demonstrated in sera from patients with systemic lupus
      erythematosus (SLE), and we now investigate the possible pathogenic effects of
      these antibodies on collagen-Fn and cell-Fn interactions. The binding of type 1
      collagen to Fn was demonstrated by ELISA, and could be specifically inhibited by
      the preincubation of solid-phase immobilized Fn with anti-Fn antibodies from SLE
      sera. By using indirect immunofluorescent staining, anti-Fn antibody containing
      SLE sera but not normal human serum (NHS) reduced the deposition of newly
      synthesized collagen and Fn on living human skin fibroblasts. We also found that
      sera from SLE patients containing anti-Fn antibodies significantly reduced
      thyroid cell attachment to Fn immobilized on plastic compared with NHS. These
      effects were shown to be due to the presence of anti-Fn antibodies in these sera,
      as SLE sera depleted of anti-Fn antibodies did not reduce the deposition of
      collagen or Fn on cultured fibroblasts, nor did they inhibit cell attachment.

PMID- 8149664
TI  - Suppression of hen egg lysozyme-induced arthritis by intravenous antigen
      administration: no role in this for antigen-driven bystander suppression.
AB  - The induction of tolerance, particularly by intervention before established
      immunity, is widely accepted. We studied the effects of intravenous (i.v.)
      administration of hen egg lysozyme (HEL), before as well as after immunization,
      on a HEL-induced arthritis. Arthritis and also cartilage destruction were almost
      completely suppressed when 100 micrograms HEL was injected before immunization.
      Antigen-specific proliferative T cell responses and IL-2 production in vitro were
      inhibited. Antigen-specific immunoglobulin and IgG1 titres were equal in control
      and tolerized mice, in contrast to lowered IgG2a titres in tolerized animals.
      Detailed histological studies showed that the immune complex-dependent
      polymorphonuclear cell phase (< 24 h after arthritis induction) was equal for
      control and HEL-injected mice. Only in the T cell-dependent phase of the
      arthritis (> 24 h), did suppression become pronounced in tolerized mice. I.v.
      administration of 100 micrograms HEL after immunization could only marginally
      reduce infiltrate and exudate, and no reduction of cartilage destruction was
      seen. An elegant way to interfere in an established immunity can be offered by
      creation of bystander suppression. We show that i.v. administration of HEL
      followed by triggering with HEL, at the moment either of immunization or of
      arthritis induction, does not reduce a methylated bovine serum albumin (BSA)
      arthritis. We conclude that arthritis can be suppressed almost totally when HEL
      is injected intravenously before immunization. Treatment after immunization is
      less effective. The i.v. induced suppression is T cell-mediated and and antigen
      specific: no bystander suppression circuit can be generated.

PMID- 8149666
TI  - Qualitative and quantitative analyses of the antibody response elicited by
      Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates
      in adults with IgG subclass deficiencies and frequent infections.
AB  - Twenty-one IgG subclass-deficient adult patients with repeated infections of the
      respiratory tract, were immunized with Haemophilus influenzae type b capsular
      polysaccharide (HibCP) covalently bound to tetanus toxoid (TT). Specific
      immunoglobulin and IgG subclasses to HibCP and TT were quantified; the biological
      activities of HibCP antibodies were also investigated. Most patients showed an
      antibody response similar to that observed in healthy adults, and the
      bactericidal activity related to the post-immunization levels of HibCP
      antibodies. No relation was found between immunoglobulin isotype deficiency, the
      clinical symptoms and the IgG subclass responsiveness, and no relation was
      observed between HibCP and TT antibody responses. Our data indicate that some,
      but not all, patients with recurrent infections and IgG subclass deficiency have
      an abnormal serum antibody response to polysaccharide and protein epitopes of Hib
      TT conjugate vaccine. Analysis of the antibody response after vaccination with
      HibCP-TT conjugate vaccine did not seem to predict the clinical course of such
      patients.

PMID- 8149665
TI  - Failure in antigen responses by T cells from patients with common variable
      immunodeficiency (CVID).
AB  - Antigen-driven responses by T cells from patients with CVID and normal subjects
      have been assessed. Low-density cells enriched for antigen-presenting dendritic
      cells were cultured with T cells using a 20-microliters hanging drop system. T
      cells from all subgroups of CVID patients showed markedly reduced responses to
      the recall antigens purified protein derivative (PPD) or tetanus toxoid, whereas
      responses by cells from patients with X-linked agammaglobulinaemia, used as a
      disease control, were in the normal range. However, primary allo-stimulation of
      CVID T cells was normal. CVID cells from two patients failed to respond to
      stimulation with a neoantigen, an HIV env peptide, under conditions where normal
      T cells did respond. These data illustrate a profound defect in antigen
      stimulated T cell proliferation in vitro in all groups of CVID patients, but do
      not distinguish whether the defect is in the presenting cell or in the T
      lymphocyte. In vivo, germinal centre B cells are thought to present antigen to
      primed T cells to obtain essential signals (e.g. CD40 ligand and IL-2) for B cell
      survival and progression to immunoglobulin secretion. A failure of antigen
      specific T cell function in vivo in CVID would thus not provide the primed T
      cells needed for B cell rescue, and could be the primary defect leading to the
      low immunoglobulin production in this condition.

PMID- 8149667
TI  - Increased levels of interferon-gamma (IFN-gamma), IL-4 and transforming growth
      factor-beta (TGF-beta) mRNA expressing blood mononuclear cells in human HIV
      infection.
AB  - Evidence has been presented for the involvement of IFN-gamma, IL-4 and TGF-beta
      in AIDS. Measured plasma levels may, however, poorly reflect in vivo production,
      since cytokines act auto- and paracrinally and have very short half life in
      plasma. In situ hybridization with complementary DNA oligonucleotide probes was
      used to enumerate blood mononuclear cells expressing cytokine messenger RNA
      (mRNA). HIV-infected patients had elevated blood levels of cells expressing each
      of the cytokines, with predominance for cells expressing TGF-beta mRNA. All AIDS
      patients included had elevated numbers of IL-4 mRNA-expressing cells, and levels
      of cells expressing this cytokine correlated inversely with counts of CD4+ cells
      in blood, reflecting the involvement of Th2-like cells in later stages of HIV
      infection. The described approach should be useful in further studies of
      cytokines in HIV infection and other diseases.

PMID- 8149668
TI  - The significance of the pre-challenge immune status of mice for development of
      retrovirus-induced immunodeficiency syndrome (MAIDS).
AB  - The effects of vaccination with RNA-free viral pseudoparticles, preinfection with
      non-pathogenic ecotropic virus, and induction of tolerance to viral proteins in
      newborns on the outcome of murine immunodeficiency syndrome (MAIDS) were studied.
      The parameters used to follow disease progression were: lymphopenia, circulating
      B and T8 cells, serum IgG and IgM levels, lymphoproliferation and skin graft
      rejection. Immunization with RNA-free viral pseudoparticles had no effect on any
      of these parameters. Preinfection of adults with ecotropic virus and the
      induction of tolerance in newborns to virus antigens both attenuated the early
      symptoms of viral infection and delayed the onset of immunodeficiency and
      lymphoproliferation in some mice, but did not significantly alter the number of
      deaths due to MAIDS. Failure of immune-based therapy to produce successful
      protection against MAIDS suggests that immune destruction caused by the
      persistent virus rather than hyperimmune activity is the main pathogenic factor
      in this disease.

PMID- 8149669
TI  - Persistence of virus and viral genome in myocardium after coxsackievirus B3
      induced murine myocarditis.
AB  - Following infection with Coxsackievirus B3 (CVB3), A-strain mice develop ongoing
      myocarditis that persists after the virus ceases to be cultivatable from heart
      tissue. We studied the natural history of this virus-induced but apparently
      autoimmune inflammation by means of in situ hybridization (ISH) and by polymerase
      chain reaction (PCR). Both ISH and culture allowed detection of virus up to 2
      weeks post-infection in virtually all heart tissues. In contrast, PCR revealed
      the presence of viral genome for a substantially longer period of time, i.e. at
      least 34 days after CVB3 infection. Similarly, the majority of mice showed
      myocardial inflammation at this time point. However, the persistence of virus did
      not correlate with ongoing myocarditis, and vice versa. Most mice with ongoing
      myocarditis produced heart myosin autoantibodies, most probably as a result of
      tissue damage. The lack of correlation between presence of ongoing inflammation
      and persistence of virus supports our previous view that the late phase of CVB3
      induced myocarditis is mediated by autoimmunological mechanisms.

PMID- 8149670
TI  - Comparison of the immune response against Mycobacterium tuberculosis antigens
      between a group of patients with active pulmonary tuberculosis and healthy
      household contacts.
AB  - The mycobacterial antigens and the factors related to protection for the
      development of active tuberculosis are not known. In a natural model of
      tuberculosis, we studied 10 patients with active pulmonary tuberculosis (non
      protective immune response) and 38 healthy household contacts (protective immune
      response). We tested the lymphocyte proliferative response by T cell Western
      blotting to eight different antigen fractions and to two purified mycobacterial
      antigens of 30 and 64 kD. Patients with active tuberculosis recognized fractions
      with molecular weights of 80-114, 60-80, 28-41 and 14-19 kD. Household contacts
      recognized the same fractions except the 14-19 kD. The response to the 64-kD
      antigen was not significantly different between groups. In contrast, 10% of the
      patients with active tuberculosis and 73% of the household contacts responded to
      the 30-kD antigen. The humoral response against the 30-kD antigen by ELISA showed
      a significantly higher production of antibodies in tuberculosis patients compared
      with household contacts. We conclude that patients with active pulmonary
      tuberculosis develop an immune response characterized by poor proliferative
      response to the 30-kD antigen with a strong humoral response, whereas the
      opposite occurs in healthy subjects infected by Mycobacterium tuberculosis.

PMID- 8149671
TI  - Cellular and humoral immune responses to recombinant 65-kD antigen of
      Mycobacterium leprae in leprosy patients and healthy controls.
AB  - Cellular and humoral immune responses to recombinant 65-kD antigen of
      Mycobacterium leprae (rML65) were studied in leprosy patients and healthy
      contacts from a leprosy-endemic population. Peripheral blood mononuclear cells
      from a considerable proportion of tuberculoid leprosy patients, healthy contacts
      and non-contacts showed proliferative response to rML65 in vitro. A strong
      positive correlation was observed between the responses to rML65 and bacille
      Calmette-Guerin (BCG) or leprosin A. Addition of recombinant IL-2 (rIL-2)
      enhanced the proportion of responders to rML65 considerably in all groups of
      leprosy patients, healthy contacts and non-contacts. Among lepromatous patients
      this enhancement was more pronounced in the bacterial index (BI)-negative group.
      These results indicate that the 65-kD antigen of Myco. leprae is a dominant T
      cell immunogen in our study population. Though lepromatous patients showed poor
      lymphoproliferative response to rML65, their IgG antibody levels to the same
      antigen were markedly high. Most of the BI-positive lepromatous patients with
      elevated anti-rML65 IgG levels did not show T cell reactivity even with the
      addition of rIL-2. On the other hand, tuberculoid leprosy patients, healthy
      contacts and non-contacts showed good T cell reactivity but low levels of IgG
      antibodies to rML65, thus indicating the presence of an inverse relationship
      between cell-mediated and humoral immune responses to a defined protein antigen
      of Myco. leprae in humans. A significant proportion of individuals among
      tuberculoid leprosy patients, healthy contacts and non-contacts showed neither T
      cell reactivity nor elevated levels of IgG antibody to rML65. However, in most of
      these subjects, a T cell response to rML65 was demonstrable with the addition of
      rIL-2. These results are discussed with reference to the immunoregulatory
      mechanisms occurring during Myco. leprae infection on the basis of differential
      activation of Th1 and Th2 subsets.

PMID- 8149672
TI  - T cell reactivity against antigen 85 but not against the 18- and 65-kD heat shock
      proteins in the early stages of acquired immunity against Mycobacterium leprae.
AB  - T cell proliferation and interferon-gamma (IFN-gamma) production of peripheral
      blood mononuclear cells (PBMC) from 20 household contacts were tested against the
      18- and 65-kD heat shock proteins from Mycobacterium leprae (ML18 and ML65
      respectively) and antigen 85 from Myco. bovis bacille Calmette-Guerin (BCG) (Ag
      85) during a 12-months follow-up study. Among the eight contacts that became
      positive, eight showed positive reactivity against Ag 85, 5/8 against ML65 and
      4/8 against ML18 at the end of the study. Of the 16 contacts who were lepromin
      positive either at first or second testing, all responded to Ag 85, 11 to ML 65,
      but only eight reacted to ML18 antigen. Contacts who were lepromin-positive at
      first testing developed responses to ML18 only at second testing. In contrast,
      among the four contacts that remained lepromin-negative during the follow up,
      three proliferated to Ag 85 either at first or second testing, but only one
      produced IFN-gamma against Ag 85 at the end of the study. These results
      demonstrated that T cell reactivity and particularly IFN-gamma secretion against
      Ag 85, but not against ML18 and ML65, might be a predominant mechanism in the
      early stages of acquired protective immunity against Myco. leprae.

PMID- 8149673
TI  - Oral and aerosol immunization with viable or inactivated Actinobacillus
      pleuropneumoniae bacteria: antibody response to capsular polysaccharides in
      bronchoalveolar lavage fluids (BALF) and sera of pigs.
AB  - To investigate the antibody response after local application of lung-pathogenic
      bacteria, pigs were immunized with viable or inactivated Actinobacillus
      pleuropneumoniae by the oral and aerogenous route. After 3 weeks class-specific
      immunoglobulins against purified A. pleuropneumoniae capsular polysaccharides
      (CP) were determined in serum and BALF by ELISA. A significant increase of IgA
      antibodies was found in BALF but not in sera of all immunized pigs. Oral
      immunization with viable A. pleuropneumoniae and aerosol immunization with either
      viable or inactivated bacteria resulted in a significant increase of IgG
      antibodies to the CP antigen in BALF, whereas only aerosol exposure to viable
      bacteria resulted in a significant increase in IgG antibodies in serum. A
      significant increase in anti-CP IgM in BALF was observed after aerosol exposure
      but not after oral immunization. IgM antibodies towards CP increased
      significantly by both routes of immunization with viable bacteria. The anti-CP
      activity of all three isotypes in sera and BALF was low in all groups compared
      with the positive controls, although inoculation of viable A. pleuropneumoniae
      led to higher levels of antibody concentration than inactivated bacteria. Our
      results indicate a traffic of primed lymphocytes from the gut into the
      bronchoalveolar airways and further support the hypothesis that polysaccharide
      specific B cells may functionally mature at the mucosal surfaces.

PMID- 8149674
TI  - Increased plasma levels of soluble IL-2R are associated with severe Plasmodium
      falciparum malaria.
AB  - Plasma samples from children with mild and severe Plasmodium falciparum malaria
      and from children with unrelated diseases were collected to investigate whether
      the clinical outcome of infection was associated with plasma factors which
      reflected the activity of different cells of the immune system. Children with
      severe P. falciparum malaria had significantly higher plasma levels of soluble IL
      2R than children with mild malaria. Plasma levels of IL-2R and levels of
      parasitaemia were significantly correlated. Neither parasitaemia nor plasma
      levels of tumour necrosis factor-alpha (TNF-alpha), IL-6, lymphotoxin (LT),
      interferon-gamma (IFN-gamma), IL-4, soluble IL-4R or soluble CD8 differed
      significantly between the two groups of children with malaria. High plasma levels
      of soluble CD8 were associated with failure of lymphocytes to produce IFN-gamma
      in vitro following stimulation with P. falciparum antigen. We conclude that
      soluble IL-2R is a useful marker of disease severity independently of the
      association with levels of parasitaemia, and that functional regulation of
      different lymphocyte subsets occurs during acute malaria episodes.

PMID- 8149675
TI  - The nonsedating antihistamine scare.

PMID- 8149676
TI  - Prognosis during one year of follow-up after acute myocardial infarction with
      emphasis on morbidity.
AB  - Previous descriptions of the prognosis after acute myocardial infarction (AMI)
      have mainly included patients admitted to coronary care units, often with an
      upper age limit. This study describes the prognosis, with emphasis on morbidity,
      during 1 year in 921 patients admitted to one single hospital with AMI regardless
      of age and regardless of whether or not they were admitted to the coronary care
      unit. During the first year, 29% of the patients died and 16% developed a
      reinfarction. Fifty-four percent required rehospitalization for various reasons,
      mainly for AMI, chest pain of other origins, and congestive heart failure. After
      1 year, 52% of the surviving patients had symptoms of angina pectoris. Among
      patients younger than 65 years, only 37% were back to work full time after 1
      year. Of patients alive after 1 year, 25% fulfilled the following criteria: no
      reinfarction, no rehospitalization, and no angina pectoris. Of patients aged less
      than 65 years at follow-up, 12% fulfilled the same criteria and were back to work
      full time after 1 year. In this unselected, consecutive series of patients with
      AMI, mortality and morbidity were high during the first year. Only a small
      percentage of patients were free of events or symptoms of angina pectoris.

PMID- 8149677
TI  - I-123 metaiodobenzylguanidine--thallium-201 mismatch following myocardial
      infarction.
AB  - Experimental data show that myocardial infarction (MI) results in regional
      depletion of myocardial catecholamines more extensively than necrosis. To
      investigate the extent of adrenergic denervation post MI in humans, we examined
      16 patients, 59 +/- 12 years old, with recent (7-12 days) MI. Resting thallium
      201 (201Tl) single photon emission computerized tomography (SPECT) imaging was
      performed to assess necrosis; metaiodobenzylguanidine I123 (MIBG) SPECT was used
      to evaluate adrenergic denervation. 201Tl and I123 MIBG defects were evaluated
      quantitatively using polar maps, and differences in defects were expressed as
      percent of total polar map. In all patients, I123 MIBG defect was larger than
      201Tl defect, and difference ranged from 19 to 61% (39.5 +/- 13.2%). Thrombolysis
      and age > 60 did not influence the difference. Anterior MI showed larger
      differences (44 +/- 13 vs. 32 +/- 11%, p < 0.05); patients with ischemic
      electrocardiographic (ECG) changes in leads without abnormal Q waves had larger
      differences (45 +/- 9 vs. 33 +/- 14%, p < 0.05). It was concluded that (a)
      patients with recent MI present denervation larger than 201Tl perfusion defect,
      and (b) patients with anterior MI and ischemic ECG changes present a larger area
      of denervation.

PMID- 8149678
TI  - Activation of leukocytes and of the kallikrein-kinin system in patients with
      unstable angina pectoris.
AB  - We investigated the leucocyte-elastase and the activity of the kallikrein system
      including kinin precursors and plasma inhibition levels in 14 patients with
      unstable angina pectoris (normal or only slightly elevated creatinine kinase
      levels; no transmural myocardial infarction) and compared them with 10 controls.
      Leucocyte-elastase levels and activity of the kallikrein system were
      significantly elevated in unstable angina pectoris. The bradykinin precursor high
      molecular-weight kininogen was markedly decreased to 79 +/- 16% indicating kinin
      generation. Except for a slight decrease in the beta factor XIIa inhibition, we
      observed no abnormalities in the plasma kallikrein inhibition or in the
      antithrombin III levels in patients with unstable angina pectoris. The findings
      indicate a significant activation of the plasma kallikrein-kinin system, which is
      not associated with a considerable reduction in the plasma inhibitor levels.
      Kinin generation might influence vascular tone and leucocyte function and thus be
      involved in the pathophysiologic alterations occurring in patients with recurrent
      angina at rest.

PMID- 8149679
TI  - Thrombolytic retreatment with tissue plasminogen activator for threatened
      reinfarction and thrombotic coronary reocclusion.
AB  - Following successful coronary arterial thrombolysis, thrombogenic substrate
      persists, increasing the risk of recurrent thrombosis, reocclusion, and
      reinfarction. The preferred treatment in this setting has not been established.
      Although many patients receive mechanical revascularization, it is conceivable
      that repeat thrombolysis, primarily with tissue plasminogen activator, represents
      the most readily available and effective alternative.

PMID- 8149681
TI  - A new approach to the management of infected pacemakers.
AB  - Management of infected pacemakers always presents a problem. This report
      describes a method of managing infected pacemakers, using the infected unit as a
      temporary pacer. This method has worked well in four patients.

PMID- 8149680
TI  - The utility of Nitroderm TTS in angina pectoris: long-term treatment after
      switching from long-acting oral isosorbide dinitrate.
AB  - Long-acting oral isosorbide dinitrate (ISDN) was replaced by Nitroderm TTS, and
      the utility of this drug in long-term treatment was assessed in 69 patients with
      angina pectoris. The frequency of attacks (p < 0.001) and the consumption of
      sublingual nitrate tablets (p < 0.01) were found to be significantly lower at 2
      weeks to 6 months than in the observation period in patients who experienced
      attacks or received sublingual tablets during the observation period. On the
      other hand, no significant time-lapse changes from the observation period were
      noted in patients who experienced no attacks or received no sublingual tablets
      during the observation period. The symptoms of adverse effects were mild. The
      improvement rates (improved) of subjective symptoms and electrocardiogram (ECG)
      in Group A were about 50% after 6 months. On the other hand, the improvement
      rates (not aggravated) of subjective symptoms and ECG in Group B were more than
      90%. Nitroderm TTS is considered a useful plaster preparation which can be used
      for sufficiently extended periods of time because its efficacy was as high as, or
      higher than, that of oral ISDN when this drug was administered over a long period
      of time after a switch from long-acting oral ISDN in angina pectoris patients.

PMID- 8149682
TI  - General concepts in the morphologic assessment of operatively excised cardiac
      valves--Part I.
AB  - This two-part article discusses the general morphologic assessment of operatively
      excised cardiac valves and applies these principles to functional
      classifications. All cardiac valves are categorized into stenotic and purely
      regurgitant (no element of stenosis) groups based upon structural features:
      presence or absence of commissural fusion, calcific deposits, and degree and
      location of fibrosis. Of 2980 operatively excised cardiac valves reviewed between
      1962 and 1992, the most common lesion was aortic stenosis, followed by mitral
      stenosis and the combination of aortic and mitral stenosis.

PMID- 8149683
TI  - Termination of pacemaker-mediated tachycardia by adenosine.
AB  - A 30-year-old woman was referred for follow-up right- and left-heart
      catheterization 4 years after cardiac transplantation. She had an implanted
      epicardial pacemaker for bradycardia; this was programmed to the DDD mode. At the
      time of her catheterization, as a pigtail catheter was pulled back across the
      aortic valve, runs of premature ventricular complexes occurred and tachycardia
      with ventricular pacing spikes and ventricular capture was initiated at a rate of
      126 beats/min. Adenosine 6 mg was given intravenously through a femoral venous
      sheath and within 20 s the tachycardia broke. The tachycardia was consistent with
      pacemaker-mediated tachycardia (PMT), a circus movement tachycardia occurring
      when ventricular pacing causes retrograde atrial depolarization followed by
      triggering of ventricular pacing. With reprogramming of the pacemaker to an AV
      delay of 160 ms and a postventricular atrial refractory period of 300 ms, no
      further episodes of PMT have occurred. This case illustrates that intravenous
      adenosine can effectively terminate PMT by causing ventriculoatrial block, thus
      interrupting the reentrant circuit by eliminating retrograde atrial activation.

PMID- 8149684
TI  - Henry T. Bahnson.

PMID- 8149685
TI  - Changes in the anterior chamber of the eye during acute hypoglycaemia in humans.
AB  - 1. The changes in the volume and depth of the anterior chamber of the eye during
      acute insulin-induced hypoglycaemia were examined in nine healthy non-diabetic
      subjects (aged 23-31 years). The dimensions of the anterior chamber of the eye
      were measured by a photogrammetric technique, with Polaroid photographs taken of
      the lower half of the mid-sagittal plane of the eye at an angle of 55 degrees at
      a magnification of x16. Photographs were taken before and at regular intervals
      after the induction of acute hypoglycaemia using an infusion of unmodified
      (soluble) insulin at 2.5 m-units min-1 kg-1. Plasma adrenaline was measured
      regularly throughout the study. 2. Plasma glucose fell from 4.5 +/- 0.2 mmol/l
      (mean +/- SEM) to a nadir of 1.0 +/- 0.1 mmol/l (P < 0.01), which coincided with
      the onset of the acute autonomic reaction. Plasma adrenaline rose from 0.3 +/-
      0.1 nmol/l to a peak of 3.2 +/- 0.6 nmol/l (P < 0.01) at 15 min after the
      autonomic reaction. 3. The volume of the anterior chamber decreased by 8.2% from
      284.7 +/- 21.5 microliters at baseline to 264.5 +/- 17.0 microliters (P < 0.01)
      at the onset of the autonomic reaction. No significant alteration in axial
      anterior chamber depth was evident, but peripheral anterior depth decreased from
      2.25 +/- 0.20 mm at baseline to 2.07 +/- 0.14 mm (P < 0.05) at the onset of the
      autonomic response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149686
TI  - Abnormalities in skeletal muscle metabolism in cyanotic patients with congenital
      heart disease: a 31P nuclear magnetic resonance spectroscopy study.
AB  - 1. Exercise tolerance is impaired in congenital heart disease. To examine the
      possible contribution of abnormalities in skeletal muscle bioenergetics, we used
      31P nuclear magnetic resonance spectroscopy to investigate muscle metabolism in
      10 subjects with congenital heart disease with cyanosis (median age 17.3 years)
      and in eight healthy age-matched control subjects. Spectra were collected from
      the gastrocnemius muscle at rest and during exercise and recovery. 2. In resting
      muscle there were significant elevations in cytosolic pH and in the cytosolic
      concentration of inorganic phosphate in the patients, and a strong positive
      correlation between cytosolic pH and blood haemoglobin concentration in all
      subjects. 3. During plantar flexion exercise the patients showed increased
      phosphocreatine depletion and cytosolic acidification over a shorter duration of
      exercise. The rise in calculated cytosolic ADP concentration was similar in both
      groups. 4. After cessation of exercise, the recovery half-times of
      phosphocreatine, ADP and phosphate were two to three times longer in the
      patients, and the initial rate of phosphocreatine resynthesis (a measure of the
      rate of mitochondrial ATP synthesis) was half the control value, consistent with
      a reduction in the effective maximum rate of oxidative ATP synthesis (expressed
      per volume of muscle). Also, recovery was faster in the young control subjects
      than in our earlier studies of older healthy control subjects. 5. The high
      phosphate concentration in resting muscle and the abnormalities found in exercise
      and recovery are consistent with a decrease in oxidative ATP synthesis due to
      reduced oxygen delivery by the blood in chronic hypoxaemia. The correlation
      between cytosolic pH and haemoglobin concentration remains to be explained.

PMID- 8149687
TI  - Diffusion of polyethylene glycol-400 across lipid barriers in vitro.
AB  - 1. Polyethylene glycol has been used extensively as a probe to measure passive
      small-intestinal permeability in vivo. However, there has been some uncertainty
      as to its suitability for use as an indicator of the permeation of water-soluble
      molecules across the intestinal wall because it seems to traverse the mucosa in
      much greater quantities than sugar molecules of equivalent M(r). 2. We have
      measured the permeation of polyethylene glycol-400 and lactulose from aqueous
      solution across pure lipid solvents in vitro. We found considerable transport of
      polyethylene glycol-400 across chloroform (1.03 g h-1 m-2) but no movement across
      petroleum ether. 3. However, in a separate experiment in which phospholipid (egg
      lecithin) was dissolved in the petroleum ether, permeation of polyethylene glycol
      400 did occur (0.13 g h-1 m2), implying interaction of polyethylene glycol-400
      with the phospholipid. No permeation of lactulose was seen in any of the
      experiments. 4. Our results suggest that, because of its interaction with lipid
      solvents, polyethylene glycol-400 is unsuitable as a probe to measure passive
      intestinal permeability in vivo.

PMID- 8149688
TI  - Atrial natriuretic peptide-cyclic GMP relationships in normal humans: effects of
      dietary sodium intake.
AB  - 1. The present study was designed to investigate the relationships between
      circulating atrial natriuretic peptide, plasma and urinary cyclic GMP and sodium
      excretion under basal conditions and in response to changes in dietary sodium
      intake. 2. Measurements of plasma atrial natriuretic peptide and plasma and
      urinary (24h collections) cyclic GMP, sodium and creatinine were made in (i) 30
      normotensive subjects on their normal sodium intake and (ii) 12 subjects on the
      5th day of a low and on the 5th day of a high sodium intake. 3. Plasma cyclic
      GMP, urinary cyclic GMP and fractional excretion of cyclic GMP in 30 normotensive
      subjects on their normal sodium intake were (means +/- SEM) 5.4 +/- 0.5 pmol/ml,
      434.5 +/- 31.8 pmol/min and 86.9 +/- 8.6%, respectively. There were significant
      correlations between urinary cyclic GMP and its corresponding filtered load (r =
      0.55) and between the renal clearance of cyclic GMP and that of creatinine (r =
      0.44), but there were no significant associations between circulating atrial
      natriuretic peptide and plasma cyclic GMP or the fractional excretion of cyclic
      GMP or between urinary sodium and the fractional excretion of cyclic GMP. 5.
      Plasma atrial natriuretic peptide was significantly raised on the 5th day of the
      high sodium intake compared with the low sodium intake (10.6 +/- 1.6 versus 4.2
      +/- 0.9 pg/ml; P < 0.05). Similarly, there were increases in urinary cyclic GMP
      excretion (692.3 +/- 43.4 versus 427.4 +/- 41.9 pmol/min, P < 0.05), but there
      were no significant differences in the fractional excretion of cyclic
      GMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149689
TI  - Renal and hormonal effects of chronic inhibition of neutral endopeptidase (EC
      3.4.24.11) in normal man.
AB  - 1. Acute pharmacological inhibition of the enzyme neutral endopeptidase (EC
      3.4.24.11), which cleaves the cardiac hormone atrial natriuretic peptide, raises
      endogenous levels of the hormone. Short-term administration of inhibitors causes
      natriuresis and diuresis in normal and hypertensive subjects; we report here the
      effects of an orally active neutral endopeptidase inhibitor (candoxatril, 200 mg)
      given twice daily for 10 days to normal salt-replete male subjects (n = 12) in a
      placebo-controlled cross-over study. 2. Candoxatril administration caused a
      transient natriuresis on day 1 of treatment, but this was not sustained, and
      cumulative sodium excretion at the end of the study was not altered by active
      therapy [1720 +/- 40 versus 1734 +/- 57 (placebo) mmol; means +/- SEM];
      exchangeable body sodium content was similarly unchanged. However, urinary cyclic
      GMP excretion was elevated throughout the active treatment phase when compared
      with placebo. 3. Although a change in plasma levels of atrial natriuretic peptide
      could not be demonstrated, platelet atrial natriuretic peptide binding sites were
      reduced by active treatment [23 +/- 3 versus 39 +/- 4 (placebo) fmol/10(9); P <
      0.001]. 4. Basal blood pressure and heart rate were not affected by candoxatril
      treatment. After 10 days of therapy subjects were given incremental infusions of
      angiotensin II (2, 4 and 8 ng min-1 kg-1) followed by phenylephrine. Although
      active therapy had not altered basal plasma concentrations of active renin and
      angiotensin II, levels of angiotensin II during infusion of the octapeptide were
      higher during the active phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149690
TI  - Early increase in glomerular leucocyte number after a reduction in renal mass:
      implications for the pathogenesis of glomerulosclerosis.
AB  - 1. Adult female Wistar rats underwent uninephrectomy (n = 8) through a flank
      incision, or a sham operation (n = 7). One to two weeks later the kidney was
      perfused in situ and glomeruli were isolated from cortical tissue by sequential
      sieving, and partially digested. Glomerular leucocytes were labelled with a mouse
      monoclonal antibody against leucocyte common antigen followed by a fluorescein
      labelled anti-mouse immunoglobulin to allow counting. 2. In a further group of
      animals 24 h albumin excretion and glomerular size were measured 2 weeks after
      either uninephrectomy (n = 6) or sham operation (n = 6). 3. Glomerular leucocyte
      number was significantly increased in uninephrectomized animals (15.7 +/- 0.9
      versus 8.9 +/- 0.4, P < 0.001), with some glomeruli having leucocyte numbers
      comparable with those seen in glomerulonephritis. 4. Albuminuria was not
      increased 2 weeks after uninephrectomy (233 +/- 35 versus 170 +/- 42
      micrograms/24 h, not significant), and glomerular size was unchanged. Light
      microscopical appearance was normal. 5. An increase in glomerular leucocyte
      number is an early response in what was previously considered a non-immunological
      lesion. It precedes the development of renal scarring and may be important in the
      pathogenesis of this process.

PMID- 8149691
TI  - Separate effects of urinary chondroitin sulphate and heparan sulphate on the
      crystallization of urinary calcium oxalate: differences between stone formers and
      normal control subjects.
AB  - 1. Urinary glycosaminoglycans were recovered from the papain digest of polyanions
      precipitated sequentially by cetylpyridinium chloride and sodium acetate
      saturated ethanol. Those from the early morning urine of 48 stone formers and 43
      normal control subjects measured 11 and 16 micrograms of uronic acid/ml of urine,
      respectively. 2. Preparative agarose gel electrophoresis of the recovered
      glycosaminoglycans in barium acetate buffer (pH 5.8) yielded fractions containing
      purely chondroitin sulphate, co-polymeric chondroitin/dermatan sulphates and
      heparan sulphate. Identification was based on the susceptibility of the fractions
      to chondroitinase or nitrous acid treatment. Similar compositions of
      glycosaminoglycan classes were observed in samples from stone formers and normal
      control subjects. 3. The fractionated glycosaminoglycans were dissolved in urine
      ultrafiltrate to assay for nucleation-promoting and growth-inhibiting activities
      towards crystallization of urinary calcium oxalate. When compared at the same
      uronic acid concentration, both the urinary chondroitin sulphate isomers and
      heparan sulphates of stone formers demonstrated the capacity to enhance crystal
      nucleation from calcium oxalate endogenous in urine ultrafiltrates, whereas only
      urinary heparan sulphates of normal control subjects demonstrated this capacity.
      4. Tissue-derived reference chondroitin sulphate, dermatan sulphate and heparin,
      when similarly tested, showed negligible crystal nucleation-promoting activity.
      The tissue-derived heparan sulphate was similar to the urinary heparan sulphates
      in showing marked crystal nucleation-promoting activity. 5. Crystal-growth
      inhibitory activity was evident in all urinary glycosaminoglycan fractions
      studied. In particular, urinary heparan sulphate of normal control subjects
      showed higher activity than that of stone formers or the chondroitin sulphate
      isomers of both stone formers and normal control subjects (P < 0.005).

PMID- 8149692
TI  - Abnormal urate transport in erythrocytes of patients with idiopathic calcium
      nephrolithiasis: a possible link with hyperuricosuria.
AB  - 1. The demonstration of an inheritable anomaly of erythrocyte oxalate transport
      in 'primary' calcium nephrolithiasis suggested that this disease might be a
      generalized metabolic disorder characterized by a defect in cellular anion
      transport. 2. To determine whether this anomaly is restricted to oxalate alone,
      we studied erythrocyte transmembrane urate self-exchange in calcium-oxalate renal
      stone formers in whom urinary excretion of uric acid is frequently increased. 3.
      Abnormal urate self-exchange was found in 30% of the patients. The urate self
      exchange rate constant was correlated with 24 h urinary excretion of uric acid;
      the erythrocyte anomaly was also associated with the frequency of hyperuricosuria
      and a more intense disease activity. Transmembrane urate self-exchange was
      inhibited by stilbene and heparan sulphate. Morphazinamide administration did not
      reduce urinary urate excretion in patients with abnormal urate erythrocyte self
      exchange. 4. These findings suggest that hyperuricosuria during calcium-oxalate
      renal stone disease might be due to a cellular defect in urate transport, and
      further support the hypothesis that idiopathic nephrolithiasis is a metabolic
      disorder characterized by a defect in cellular anion transport.

PMID- 8149693
TI  - Variability of cardiovascular and plasma noradrenaline responses to sustained
      isometric contraction in normal human subjects.
AB  - 1. Eight healthy adult males underwent three sustained isometric contractions at
      30% of maximal voluntary contraction for 3 min, within a 9 day period. 2. The
      study focuses on the inter-individual and day-to-day intra-individual variability
      of cardiovascular and plasma noradrenaline responses to sustained isometric
      contraction. 3. The results of this study indicate that inter-individual
      variability is generally greater than intra-individual variability. Diastolic
      blood pressure was the most sensitive as well as the least variable
      cardiovascular parameter measured. 4. The variability of plasma noradrenaline
      levels in both the basal and the stimulated state was high. The present study
      suggests that it is preferable to determine the 'true' noradrenaline peak after
      the release of handgrip, as this is associated with a lower variability than the
      plasma noradrenaline peak taken at the time of the release of handgrip.

PMID- 8149694
TI  - Dose-response effects of adrenergic and cholinergic stimulation on atrial
      natriuretic peptide secretion from beating isolated guinea-pig atria.
AB  - 1. The possible role of autonomic neurotransmitters in atrial natriuretic peptide
      secretion was investigated using spontaneously beating guinea-pig atria in vitro.
      Dose responses were determined for adrenaline, noradrenaline and acetylcholine
      and the selective alpha- and beta-adrenoceptor agonists phenylephrine and
      isoprenaline, respectively. Adrenoceptor effects were further studied using the
      selective alpha- and beta-adrenoceptor antagonists prazosin and propranolol,
      respectively, in conjunction with maximal adrenaline challenge. Results for rate
      and force of contraction and atrial natriuretic peptide secretion are expressed
      as a ratio (mean +/- SEM) of a 15 min treatment period (stage 2) to a
      corresponding pretreatment period (stage 1). 2. Adrenaline and noradrenaline
      caused dose-dependent increases in the rate and force of contraction and in
      atrial natriuretic peptide secretion with a peak secretory response at 2 x 10(-6)
      mol/l of 1.54 +/- 0.08 (P < 0.01) and 1.34 +/- 0.08 (P < 0.01) for adrenaline and
      noradrenaline, respectively. Acetylcholine decreased the rate and force of
      contraction, and ANP secretion was reduced to 0.47 +/- 0.06 at 3 x 10(-5) mol/l
      (P < 0.01). Isoprenaline increased the rate and force of contraction and atrial
      natriuretic peptide secretion with a peak secretory response of 1.52 +/- 0.22 at
      2 x 10(-6) mol/l (P < 0.01). Phenylephrine increased the force but had no effect
      on the rate of contraction, and stimulated atrial natriuretic peptide secretion
      to 1.13 +/- 0.09 at 2 x 10(-5) mol/l (P < 0.05). After both alpha- and beta
      adrenoceptor blockade, adrenaline was still able to significantly stimulate
      atrial natriuretic peptide secretion and positive inotropy.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8149695
TI  - Effect of chronic smoking on endothelium-dependent vascular relaxation in humans.
AB  - 1. Cigarette smoking is one of the major risk factors for the development of
      atherosclerosis. It is not clear, however, whether chronic cigarette smoking
      impairs the normal physiological function of the endothelium before the
      development of morphological vascular lesions. To test this, we investigated
      endothelium-dependent vascular relaxation in young habitual smoking subjects. 2.
      In 11 non-smokers and 10 habitual smokers we measured the changes in bilateral
      forearm blood flow, arterial blood pressure and forearm vascular resistance
      (ratio between mean arterial blood pressure and forearm blood flow) during three
      interventions: post-occlusive forearm hyperaemia, intrabrachial infusion of
      methacholine which causes vasodilatation by stimulating the release of
      endothelium-dependent relaxing factor, and intrabrachial infusion of sodium
      nitroprusside which causes vasodilatation independently from the endothelium by a
      direct effect on the vascular smooth muscle wall. 3. During infusion of the
      highest dose of methacholine, forearm vascular resistance decreased by 91.7 +/-
      1.4% in the smokers and by 89.9 +/- 1.8% in the non-smokers. During infusion of
      sodium nitroprusside, forearm vascular resistance decreased by 80.0 +/- 3.8% in
      the smokers as compared with 80.7 +/- 6.1% in the non-smokers. There was no
      difference in basal forearm vascular resistance or in post-ischaemic reactive
      hyperaemia between smokers and non-smokers. Thus, vasodilatation induced by both
      methacholine and sodium nitroprusside was not significantly different between
      smokers and non-smokers. 4. We conclude that in young habitual cigarette smokers
      the endothelium-dependent vasodilation in the forearm seems to be preserved,
      suggesting that habitual smoking does not result in permanent endothelial
      dysfunction in the human forearm.

PMID- 8149696
TI  - Mitogenic events induced by vasopressin in aortic fibroblasts from spontaneously
      hypertensive rats.
AB  - 1. To further explore the mechanisms of arterial growth, we investigated the
      signalling pathways through which arginine-vasopressin acts as a mitogen in
      cultured adventitial aortic fibroblasts of the spontaneously hypertensive rat,
      and we examined the mechanisms involved in the hyperresponsiveness to arginine
      vasopressin of fibroblasts from spontaneously hypertensive rats compared with
      fibroblasts from Wistar-Kyoto rats. 2. Arginine-vasopressin-induced [3H]thymidine
      incorporation was used to determine the peptide mitogenicity. Arginine
      vasopressin-triggered hydrolysis of phosphoinositides by phospholipase C was
      evaluated by measuring [3H]inositol phosphate formation. The role of protein
      kinase C and protein tyrosine kinases in arginine-vasopressin mitogenicity was
      assessed by stimulating the cells with arginine-vasopressin in the presence of 12
      O-tetradecanoylphorbol 13-acetate and tyrphostin (a tyrosine kinase inhibitor),
      respectively. 3. Arginine-vasopressin-induced DNA synthesis was completely
      abolished in confluent cells, whereas [3H]inositol phosphate formation was only
      reduced. The presence of 12-O-tetradecanoylphorbol 13-acetate markedly decreased
      arginine-vasopressin-induced [3H]thymidine incorporation in fibroblasts from
      spontaneously hypertensive rats and was without effect in fibroblasts from Wistar
      Kyoto rats. Tyrphostin abolished arginine-vasopressin-induced [3H]thymidine
      incorporation in a dose-dependent manner and did not affect the formation of
      inositol phosphates. 4. These results indicate that phospholipase C activation is
      not sufficient for arginine-vasopressin-induced mitogenesis. They also suggest
      that (i) tyrosine kinase activation is a necessary step in the transduction of
      the arginine-vasopressin mitogenic signal, and (ii) protein kinase C participates
      in the increased mitogenic potency of arginine-vasopressin in spontaneously
      hypertensive rats.

PMID- 8149697
TI  - Neutrophil platelet-activating factor in normal and hypertensive pregnancy and in
      pregnancy-induced hypertension.
AB  - 1. Platelet-activating factor is a phospholipid with potent vasodilator and
      platelet-activating properties. To test the hypothesis that a generalized change
      in cellular platelet-activating factor metabolism may be involved in the systemic
      vasodilatation of normal pregnancy or pregnancy-induced hypertension, we studied
      platelet-activating factor and eicosanoid synthesis in isolated leucocytes
      obtained from pregnant women before and after delivery compared with age-matched
      non-pregnant control subjects. Parallel observations were carried out in age- and
      gestation-matched women with uncomplicated hypertension in pregnancy and in women
      with pregnancy-induced hypertension and a further set of normotensive pregnant
      control subjects. 2. Leucocyte counts were higher in all pregnant groups compared
      with non-pregnant control subjects. Neutrophil production of platelet-activating
      factor and metabolites of prostacyclin, prostaglandin E2 and thromboxane in
      response to calcium ionophore stimulation were all lower in pregnant women
      compared with non-pregnant control subjects, but returned to similar levels 6
      weeks post partum. There was no significant difference between essential
      hypertensive and normotensive groups. When women with pregnancy-induced
      hypertension were a priori sub-divided into those with or without proteinuria,
      subjects with proteinuria showed significantly lower levels of neutrophil
      platelet-activating factor synthesis. 3. Plasma levels of the platelet-activating
      factor metabolite (lyso-platelet-activating factor) were also lower in pregnancy,
      suggesting alterations in the activity of enzymes controlling synthesis or
      degradation of this phospholipid in pregnancy. In pregnancy-induced hypertension
      the levels of plasma lyso-platelet-activating factor were higher than in normal
      pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149698
TI  - Pulmonary vascular reactivity and ischaemia-reperfusion injury in the rat.
AB  - 1. The endothelium has been shown to modulate the pulmonary vascular response to
      hypoxia in the rat. Acute lung injury is associated with loss of hypoxic
      pulmonary vasoconstriction and increased pulmonary vascular permeability. Similar
      loss of the vascular response to hypoxia is seen after ischaemia-reperfusion
      injury of the myocardium. 2. The effects of reperfusion injury on pulmonary
      endothelial integrity, as shown by the albumin escape index and hypoxic pulmonary
      vasoconstriction, were investigated in isolated, blood-perfused rat lungs. 3.
      Ischaemia for 0.5 h, which itself caused no increase in the albumin escape index,
      was followed by reperfusion for 0.25 h, 0.5 h and 1 h. Controls were subjected to
      2 h of perfusion only (n = 5 in all groups). The pulmonary pressor response to
      hypoxia (fractional inspired oxygen concentration, 3%) was measured before and
      after ischaemia-reperfusion, and the dilator response to acetylcholine was
      measured after ischaemia-reperfusion in all cases. 4. Ischaemia-reperfusion
      significantly increased the albumin escape index after 0.5 h (mean +/- SEM, 1.40
      +/- 0.27) and 1 h (2.0 +/- 0.30) compared with controls (0.54 +/- 0.30, P < 0.05
      in both cases). The pulmonary pressor response to hypoxia was augmented
      significantly after reperfusion when compared with baseline hypoxic pulmonary
      vasoconstriction (change from baseline: 13.2 +/- 4.63 and 22.2 +/- 7.1% after 0.5
      and 1.0 h of reperfusion, respectively, P < 0.05). Vasorelaxation of sustained
      hypoxic vasoconstriction using acetylcholine was similar in both control lungs
      and those subjected to ischaemia-reperfusion. 5. These results suggest tht the
      pressor response to hypoxia is augmented after damage to the pulmonary vascular
      endothelium induced by ischaemic-reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149699
TI  - Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia
      and insulin sensitivity in diabetes mellitus.
AB  - 1. The activity of serum butyrylcholinesterase ('pseudocholinesterase',
      EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51
      patients with type 2 diabetes mellitus and 101 healthy control subjects. 2.
      Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/
      3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the
      control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with
      type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated
      with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43,
      respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase
      activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4.
      Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma
      glutamyltranspeptidase activity, body mass index, or treatment for diabetes in
      both the diabetic populations. 5. In 37 non-diabetic patients with
      butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal
      range. 6. These results are consistent with the view that butyrylcholinesterase
      may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia
      associated with insulin insensitivity or insulin deficiency in diabetes mellitus.

PMID- 8149700
TI  - Lipid metabolism after liver transplantation from a living related donor.
AB  - 1. The recovery of lipid metabolism was investigated in paediatric patients
      treated for terminal liver disease by liver transplantation from living related
      donors. 2. The cholesterol ester ratio (esterified cholesterol/total cholesterol)
      and the total cholesterol/phospholipid ratio increased from preoperative values
      of 0.35 +/- 0.04 and 0.59 +/- 0.03 to 0.65 +/- 0.01 and 0.68 +/- 0.01 at 3 weeks
      after liver transplantation in successful cases (means +/- SEM, n = 26),
      respectively, whereas these two parameters decreased in failed cases (n = 4). 3.
      Biochemical analysis indicated that weekly recoveries in the cholesterol ester
      ratio and the total cholesterol/phospholipid ratio are characteristic of
      successful liver transplantation with a graft from a living related donor.

PMID- 8149701
TI  - Venous blood arterialization and parameters from the minimal models of glucose
      disappearance and post-hepatic insulin delivery.
AB  - 1. Modelling analysis of intravenous glucose tolerance test glucose and insulin
      concentrations can provide measures of insulin sensitivity and metabolism from a
      single straightforward procedure. However, little is known of the effects of
      blood arterialization on model-derived parameters. 2. Intravenous glucose
      tolerance tests were carried out on 18 subjects, with measurement of glucose and
      insulin concentrations in simultaneously sampled non-arterialized and
      arterialized blood. Blood oxygen saturation, partial pressure of CO2 and pH were
      measured on both non-arterialized and arterialized blood during the intravenous
      glucose tolerance test. Using the minimal models of glucose disappearance and
      post-hepatic insulin delivery, measures of insulin sensitivity, glucose-dependent
      glucose disposal, first- and second-phase post-hepatic insulin responsiveness to
      glucose and plasma insulin elimination rate were derived from intravenous glucose
      tolerance test glucose and insulin concentrations in both arterialized and non
      arterialized blood. 3. During the intravenous glucose tolerance test mean blood
      oxygen saturation was 6.7% higher, partial pressure of CO2 was 0.3 kPa lower and
      pH was 0.015 higher in arterialized than non-arterialized blood. Mean parameter
      values did not differ when derived from measurements made on non-arterialized and
      arterialized blood. Model-derived parameters were not related to the degree of
      arterialization, although there was some consistent variation with sampling site
      for parameters of glucose-dependent glucose disposal (Sg), first-phase post
      hepatic insulin responsiveness (phi 1) and insulin elimination (ni). 4.
      Measurements made on non-arterialized blood are suitable for analyses employing
      the minimal models of glucose disappearance and post-hepatic insulin delivery.
      Imprecision in some parameters may be diminished by adherence to a single
      sampling site.

PMID- 8149702
TI  - Hyperproinsulinaemia in impaired glucose tolerance.
AB  - 1. Basal circulating concentrations of islet B cell products were measured using
      two-site monoclonal antibody-based immunoradiometric assays after a 10 h
      overnight fast in a group of non-obese subjects with recently diagnosed impaired
      glucose tolerance (World Health Organization criteria). A group of healthy
      subjects with normal oral glucose tolerance matched for age and body mass index
      served as normal controls. 2. Fasting blood glucose concentration was normal in
      all subjects with mean (+/- SEM) levels of 5.1 +/- 0.2 and 4.8 +/- 0.2 mmol/l (P
      > 0.1) for the group with impaired glucose tolerance and the healthy control
      group, respectively. 3. There was no significant difference (P > 0.1) in fasting
      plasma insulin or C-peptide concentrations between the groups. 4. By contrast,
      the fasting concentration of intact proinsulin was nearly four-fold higher in the
      subjects with impaired glucose tolerance than in the matched healthy control
      subjects (4.5 +/- 1.0 versus 1.2 +/- 0.2 pmol/l, P < 0.005). 5. Similarly, the
      fasting plasma concentration of 32-33 split proinsulin in the subjects with
      impaired glucose tolerance was almost twice that of the control subjects (7.4 +/-
      1.3 versus 3.9 +/- 0.8 pmol/l, P < 0.02). 6. In conclusion, fasting
      concentrations of proinsulin-like molecules are elevated in non-obese subjects
      with newly diagnosed impaired glucose tolerance. This observation is consistent
      with defective islet B cell proinsulin processing in this syndrome.

PMID- 8149703
TI  - Skin microcirculatory and thermal changes in elderly subjects with early stage of
      pressure sores.
AB  - Elderly subjects are prone to develop pressure sores over the sacrum area mainly
      due to external pressure and shear effects which negatively affect the skin
      microcirculation. The aim of the study described here was to measure skin
      microcirculatory and thermal changes in twelve elderly patients with an early
      stage of pressure sore and in ten elderly subjects without pressure sore. The
      total skin microcirculation at a damaged risk area, the sacrum, and a reference
      area of undamaged skin over the gluteal region, was evaluated using the laser
      Doppler fluxmetry. The nutritive transport of small solutes, characterized by the
      transcapillary exchange of sodium fluorescein, was evaluated using the
      fluorescein flowmetry technique. The skin temperature was measured with a
      thermoelement. The skin microcirculation at the area with an early stage of
      pressure sore was significantly higher than at undamaged skin as measured by both
      techniques. The total microcirculatory blood flow increased > 16 times (P <
      0.001) and the nutritive transport approximately 5 times (P < 0.01) compared to
      the reference value, and the calculated blood flow of subpapillary tissue layers
      increased 17-19 times (P < 0.001). However, the skin temperatures in damaged and
      undamaged skin did not differ significantly. These results show an increased skin
      microcirculation in the early stage of pressure sores but no increase in skin
      temperature. The more strongly increased skin blood flow in subpapillary tissue
      layers effectively conducts away the heat caused by the damage and the increased
      metabolic activity.

PMID- 8149704
TI  - Cytoplasmic calcium regulation and the electrocardiogram in patients with primary
      hyperparathyroidism.
AB  - Primary hyperparathyroidism (HPT) is a disease caused by an abnormal cytosolic
      regulation of calcium concentration [Ca++]i leading to an increased secretion of
      parathyroid hormone and thereby increased levels of extracellular calcium. It is
      well known that the QT-interval measured at electrocardiography (ECG) is
      shortened in HPT subjects. Whether this is due to an abnormal intracellular
      handling of calcium also in the heart or to the raised extracellular calcium
      levels is not known. In order to study the extent to which the deranged extra-
      and intracellular levels of calcium in HPT patients were related to ECG
      characteristics, [Ca++]i was determined in vitro by microfluorometry in surgery
      removed parathyroid cells at extracellular calcium concentrations of 0.5 mM and
      30.0 mM and ECG was recorded preoperatively in 42 HPT patients and in 15 subjects
      operated on for atoxic goitre. Serum calcium and plasma-ionized calcium also were
      measured preoperatively. The QT-interval and ST-segment duration were both
      shortened in the HPT patients compared to controls (P < 0.001). [Ca++]i at 3.0 mM
      extracellular calcium divided by that at 0.5 mM was correlated to the QT
      interval, when measured at the onset of the T-wave (QoT, r = 0.39, P < 0.03) and
      early diastolic phase (end of T-wave to onset of p-wave, r = -0.34, P =
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149705
TI  - Influence of shear on skin oxygen tension.
AB  - Since the early studies on decubitus many authors expect significant influence of
      shear on decubitus risk. In the study described here skin oxygen tension at the
      sacrum was measured with combined pressure and shear stress on a young healthy
      population (mean age 25.5 years, SD 3.4 years). Cut-off pressure is defined as
      the level of external pressure exerted on the skin at which the skin oxygen
      tension is 1.3 kPa. At this level ischaemia of the skin can be expected (Bar,
      1988). A mean cut-off pressure of 11.6 kPa was found when no shear stress was
      applied vs. a significantly lower mean cut-off pressure of 8.7 kPa with a shear
      stress of 3.1 kPa. No significant relationship was found between cut-off pressure
      and systolic blood pressure, diastolic blood pressure, skin thickness at the
      sacrum, percentage of fat and skin oxygen tension in the unloaded situation.

PMID- 8149706
TI  - Diameter and velocity changes in the femoral vein during thermal stress in
      humans.
AB  - Unlike most studies on deep veins performed with simultaneous suppression of
      cutaneous blood flow, a sonographic study of femoral diameter and blood flow
      velocity changes in response to thermal stress was performed while cutaneous flow
      was preserved. In 11 normal subjects, mean peak blood flow velocity and diameter
      of the femoral vein were measured at rest and during indirect whole body heating
      and cooling. Mean peak venous blood flow velocity was 0.12 +/- 0.06 m s-1 at
      rest, 0.35 +/- 0.23 m s-1 (P < 0.001) during heat stress, and 0.13 +/- 0.07 m s-1
      during cold stress (NS). Femoral venous diameter was 5.3 +/- 0.9 mm at rest, 5.1
      +/- 1.0 mm (P < 0.05) during warming, and 5.4 +/- 81.0 mm (NS) during cooling.
      This study showed a decrease in diameter during thermal stress. However, as mean
      femoral venous blood-flow velocity was doubled during heat stress, femoral venous
      blood flow was increased. Thus, it is suggested that during heat stress part of
      the increase in cutaneous flow is returned through deep veins.

PMID- 8149707
TI  - Assessment of coronary artery stenosis pressure gradient by quantitative coronary
      arteriography in patients with coronary artery disease.
AB  - The aim of the study described here was to correlate coronary artery (CA)
      stenosis pressure gradients calculated by quantitative coronary arteriography
      (QCA) to invasively measured transstenotic pressure drops in patients with
      anginal symptoms and with known or suspected coronary artery disease.
      Furthermore, the known mathematical models are improved by introducing (1)
      pressure catheter-corrected minimal stenosis area, (2) modification of flow
      assumptions, and (3) stenosis exit angle. Included in the study were 45 patients
      with 61 stenoses. The visually estimated CA lesion severity in these non-complex
      stenoses was in the equivocal range of 40-70%. All measurements were performed
      after intracoronary administration of nifedipine and nitroglycerin. Stenosis
      dimensions were assessed from magnified cinefilms, using hand-held calipers.
      Highly significant overall correlation was found between measured and calculated
      pressure gradients with correction for the impact of the intracoronary catheter
      (P < 0.00001, r = 0.84). In particular, a substantial number of stenoses with
      haemodynamically-insignificant pressure gradients were identified by hydrodynamic
      calculations. In conclusion, the great majority of the coronary artery stenoses
      could be classified reliably by QCA as being haemodynamically insignificant or
      significant, respectively.

PMID- 8149708
TI  - Cardiac output determined by the CO2 rebreathing method during arm exercise.
AB  - Since arm exercise affects the respiratory muscles the CO2 rebreathing method for
      determining cardiac output (Q) has to be evaluated during arm exercise. The
      purpose of this study was (1) to compare three different methods of determining
      arterial CO2 tension (PaCO2) during arm exercise, (2) to verify the linearity of
      the relationship between Q and oxygen uptake (VO2) during arm exercise, and (3)
      to investigate whether the CO2 rebreathing method according to Collier can
      determine accurately Q during arm exercise. Sixty male subjects performed arm
      cranking exercise at 20%, 40% and 60% of their individual maximal load. Carbon
      dioxide output (VCO2) was measured by gas exchange measurement, and mixed venous
      CO2 tension (PvCO2) was determined from the CO2 rebreathing plateau at each
      exercise level. PaCO2 was estimated in three different ways: (A) by the modified
      Bohr formula for dead space, (B) by an arterialized blood sample from the
      hyperaemic ear-lobe, and (C) by the end-expiratory CO2 tension. A, B, and C were
      used to calculate Qa, Qb and Qc, respectively. The Pearson's correlation
      coefficient was high (P < 0.01) among the three different ways of estimating
      PaCO2. The Q-VO2 relationship proved to be linear (P < 0.01). The Q-values showed
      a good agreement with the direct Fick measurements, and were in the same range
      compared to other results obtained by dye dilution, electrical impedance
      cardiography and the exponential CO2 rebreathing method during arm exercise. In
      conclusion, the CO2 rebreathing method appeared to be accurate to determine Q
      during submaximal arm exercise.

PMID- 8149709
TI  - Is transcutaneous PO2 monitoring during exercise a reliable alternative to
      arterial PO2 measurements?
AB  - Arterial PO2 measurement during exercise is an important part in the evaluation
      of pulmonary disease but requires an intra-arterial cannula. However, in clinical
      work it would be preferable to assess PO2 non-invasively. To evaluate such a
      technique, simultaneous measurements of transcutaneous PO2 (tcPO2) and arterial
      PO2 (PaO2), sampled from an indwelling arterial radial cannula, were made before,
      during and after a fatigue or symptom-limited bicycle exercise test in 16
      patients referred to hospital because of dyspnoea. In total 181 paired
      measurements were made. Mean values (range) of PaO2 and tcPO2 were 11.2 kPa (5
      16) and 9.5 (5-13.3), respectively. The correlation coefficient between PaO2 and
      TcPO2 was only 0.36 (P < 10(-5)). By normalizing the values of tcPO2 and PaO2 to
      corresponding values at supine rest before exercise, the correlation coefficient
      increased to 0.80 (P < 10(-6). Using PaO2 as golden standard, tcPO2 described the
      trend in pO2 during exercise reasonably well in all cases and this information is
      often sufficient for assessing the degree of pulmonary insufficiency. Thus,
      transcutaneous blood gas monitoring during exercise is useful for clinical
      evaluation of pulmonary disease, but a single arterial blood sample at rest
      before exercise is recommended for baseline correlation.

PMID- 8149710
TI  - Repeated measurements of transfer factor in rabbits: an animal model suitable for
      evaluation of short-term exposure.
AB  - Acute temporary changes in lung function may be of use as a biological exposure
      indicator. However, studies of humans occupationally exposed to complex airborne
      irritants are often expensive and time demanding. Therefore, an animal model
      could be a valuable complement. A rabbit model has been evaluated where transfer
      factor was measured twice during the same day, and with the rabbit awake and
      available for exposure, in between. Anaesthesia and intubation in 22 rabbits (2.6
      [0.2] kg [Mean (SD)]) were immediately followed by two measurements of transfer
      factor and alveolar volume. Transfer factor was estimated by the single breath CO
      technique used in humans. The samples were analysed for CO and He on a gas
      chromatograph. After one pair of measurements the rabbit was allowed to wake up
      and after 5 h the duplicate measurements were repeated. The mean values of
      transfer factor, alveolar volume and transfer constant were 0.50 (0.09) mmol min
      1 kPa-1, 127 (8) ml and 3.9 (0.6) mmol min-1 kPa-1 l-1, respectively. The
      intraindividual coefficients of variation were 7.3%, 5.3% and 6.7%, respectively.
      Five hours later when the duplicate measurements were repeated, transfer factor,
      alveolar volume and transfer constant were unchanged still. The results suggest
      that relatively small changes in transfer factor may be detected without losing
      power, and thus that this model could be used as a biological exposure indicator.

PMID- 8149711
TI  - Local cooling prolongs oesophageal transit in humans.
AB  - The influence of local cooling on oesophageal transit was studied in eight
      healthy volunteers by oesophageal radionuclide transit. Compared with lukewarm
      (18 degrees C) water a significantly prolonged mean transit time (MTT) was found
      after ingestion of cold liquid (4 degrees C) and a slightly shorter MTT with 50
      degrees C. The effect was of short duration lasting less than 2 min. The effect
      of atropine, morphine and naloxone, on the influence of local cooling was
      evaluated. Morphine (7 x 5 mg i.v.) abolished the effect of cooling on MTT.
      Naloxone (1 x 6 mg i.v.) reduced the effect of cooling, but the difference
      between 4 degrees C and 19 degrees C was significant still. Atropine (1 mg i.v.)
      had no effect on the increase in MTT at 4 degrees C. It is concluded that in
      humans local cooling increases oesophageal MTT. Local warming shortened MTT
      slightly. The abolishment of the influence of cooling by morphine suggests that
      opioids may be involved.

PMID- 8149712
TI  - Increased body weight in men after the age of 55 is a risk factor for internal
      carotid artery stenosis: an epidemiological study of men aged 69.
AB  - A population-based cohort of 393 men born in 1914 and residing in the city of
      Malmo, Sweden, was examined at ages 55 and 69 years, respectively, with regard to
      risk factors for arteriosclerotic vascular and coronary disease. At age 69 an
      examination of the carotid arteries with Doppler ultrasound was carried out also,
      to establish the prevalence and degree of stenosis in the carotid vessels. The
      material was analysed for the following risk factors for internal carotid artery
      stenosis: systolic and diastolic blood pressure, cholesterol, triglycerides,
      haematocrit, gamma glutamyl transferase (GT), blood glucose, body mass index
      (BMI), body weight change (BWC), and smoking. Stepwise multiple regression
      analysis showed that only increased body weight between 55 and 69 years of age
      and the earlier known risk factor, smoking, remained as independent risk factors
      for developing carotid artery disease.

PMID- 8149713
TI  - Calculation of renal extraction during high diuresis and low renal plasma flow
      conditions.
AB  - The renal fractional extraction (Ex) is a parameter describing the ability of the
      kidneys to remove a substance x from the circulating plasma. Ex is calculated
      often as the ratio between the arteriovenous concentration difference and the
      arterial concentration. This method simplifies the calculations but it is
      associated with an underestimation of Ex. In the study described here, a
      theoretical analysis of the error is made, with a graphical presentation of its
      magnitude in different diuresis/renal plasma flow (RPF) ratios and at different
      levels of Ex. The error was analysed also in a clinical situation where the renal
      extraction of PAH (EPAH) and EDTA (EEDTA) were determined in six patients during
      different stages of cardiac surgery. The underestimation of EPAH was seldom more
      than 4%, while EEDTA was underestimated often with more than 20%. It is concluded
      that the simplified formula is accurate when calculating the renal extraction for
      substances like PAH, with a normally high extraction, even if the diuresis/RPF
      ratio is high. For substances with low extractions, e.g. filtration markers, in
      some clinical and experimental situations it is necessary to take the renal
      plasma flows into consideration or to arrange for low urine production to avoid
      significant errors.

PMID- 8149714
TI  - Model for radionuclide evaluation of left-to-right ductal shunts.
AB  - A model for radionuclide evaluation of left-to-right ductal shunts was designed.
      It was a generalization of the standard Maltz-Treves method, accounting for the
      possibility that distribution of the shunt flow between the two lungs differs
      from that in the right ventricular (RV) output (Fs). This yields a new
      formulation in which the ratio of ductal flow to pulmonary flow (Fd/Fp) equals a
      weighted average of Fd/Fp obtained separately for the right lung (RL) and the
      left lung (LL), i.e. Fd/Fp = R(Fd/FpP)RL+ (1-R) (Fd/Fp)LL; where R is the
      fraction of the RV output going to the right lung. Separate shunt-flow ratios can
      be obtained by conventional analysis of the respective lung radiohistogram, while
      R can be determined from the upslopes of these curves. Formulas were derived
      rigorously from basic principles, so that the ultimate clinical validity of the
      method depends on radioangiographic assessment of R, (Fd/Fp)RL and (Fd/Fp)LL. Due
      to asymmetry of flows there is no true referent method for patients with ductal
      shunts. Therefore a simulation study, using quasi-real data, was utilized,
      yielding satisfactory performances of the algorithm: (Fp/Fs) calculated = 0.92
      (Fp/Fs)stimulated +0.15 (r = 0.878).

PMID- 8149715
TI  - Probabilities and utilities of fictional outcomes in Wason's four-card selection
      task.
AB  - Four experiments are presented that show that selections in Wason's (1966) four
      card selection task can be increased by increasing the probability that cards
      will yield important outcomes. Experiment 4 also shows that selections can be
      influenced by varying the utilities of possible outcomes. These results suggest
      that some important content effects in this task may not arise from inferential
      processes, and examples are given of how probabilities and utilities have been
      confounded with other manipulations in previous research. The recent trend
      towards content-dependent theories of reasoning may have arisen largely because
      theorists are attempting to construct models of inferential reasoning that can
      account for what are, in part, non-inferential phenomena. Content-independent
      inferential processes and content-independent choice processes may operate
      together to account for content effects in the selection task.

PMID- 8149716
TI  - Canonical linking rules: forward versus reverse linking in normally developing
      and specifically language-impaired children.
AB  - Canonical linking rules for mapping thematic roles with syntactic functions were
      studied. Three experiments were undertaken to investigate the nature of
      productive forward linking (from semantics to syntax) and productive reverse
      linking (from syntax to semantics). I proposed that reverse linking, in contrast
      to forward linking, requires more detailed specification of the syntactic
      structure; that is, a syntactic representation which specifies each particular
      syntactic frame and all the argument positions within that frame. Six
      specifically language-impaired children (aged 6;1 to 9;6) were matched on
      language abilities to 17 younger, normally developing children (language age 3;1
      to 6;6). In Experiment 1--forward linking--the children were shown the meaning of
      a novel verb and had to describe the event using the novel verb. Experiment 2--a
      comprehension task--required acting out sentences containing the newly learned
      verbs. In Experiment 3--reverse linking--the children were told a sentence with a
      novel verb and had to act out its meaning, assigning thematic roles on the basis
      of the syntactic frame. Group and individual analysis generally revealed no
      significant differences between the specifically language-impaired children and
      the language age control children in Experiments 1 and 2, but a significant
      difference was found for Experiment 3. The normally developing children showed a
      good use of productive forward and reverse linking. The specifically language
      impaired children demonstrated good productive forward linking but were
      significantly worse at reverse linking. An interpretation of the data, showing
      differences in the syntactic representation required for forward versus reverse
      linking, can account for the findings. I propose that a deficit in the area of
      "government" or "locality" which underlies c-selection and specifies the
      syntactic relationship between constituents can account for the data from this
      study and the data from previous investigations of specifically language-impaired
      children.

PMID- 8149717
TI  - A reassessment of the shift from the classical theory of concepts to prototype
      theory.
AB  - A standard view within psychology is that there have been two important shifts in
      the study of concepts and that each has led to some improvements. The first shift
      was from the classical theory of concepts to probabilistic theories, the most
      popular of which is prototype theory. The second shift was from probabilistic
      theories to theory-based theories. In this article, I take exception with the
      view that the first shift has led to any kind of advance. I argue that the main
      reasons given for preferring prototype theory over the classical theory are
      flawed and that prototype theory suffers some of the same problems that have been
      thought to challenge the classical theory.

PMID- 8149718
TI  - The influence of orthographic consistency on reading development: word
      recognition in English and German children.
AB  - Groups of 7, 8, and 9-year-old children who were learning to read in English and
      German were given three different continuous reading tasks: a numeral reading
      task, a number word reading task, and a nonsense word reading task. The nonsense
      words could be read by analogy to the number words. Whereas reading time and
      error rates in numeral and number word reading were very similar across the two
      orthographies, the German children showed a big advantage in reading the nonsense
      words. This pattern of results is interpreted as evidence for the initial
      adoption of different strategies for word recognition in the two orthographies.
      German children appear to rely on assembling pronunciations via grapheme-phoneme
      conversion, and English children appear to rely more on some kind of direct
      recognition strategy. A model of reading development that takes account of
      orthographic consistency is proposed.

PMID- 8149720
TI  - Collaborative evaluation of a volunteer monitoring program to improve group homes
      for adults with mental retardation.
AB  - This report describes an evaluation study of a volunteer monitoring program
      designed to improve the quality of life in group homes for adults with mental
      retardation. Special attention is given to the evaluation researchers' efforts to
      collaborate with the volunteer monitors to develop valid measures and a research
      design that would minimize the inherent threats to validity (e.g., selection
      biases). Initial results noted (a) the frequency in which 257 volunteers
      monitored 248 group homes in Michigan and (b) the homes that were visited three
      or more times over the course of this study had lower normalization levels than
      the home visited only once or twice. The impact of the program was tested using a
      repeated measures design with a subsample of 79 homes that were monitored on at
      least four occasions. The evaluation results suggested that frequent monitoring
      was associated with improvements in the homes' decor, the residents' appearance,
      and the social interaction styles in the homes.

PMID- 8149719
TI  - Psychiatric disorders among elderly Koreans in the United States.
AB  - This study examines the lifetime prevalence of various psychiatric disorders
      among 100 Korean elderly in Los Angeles. The instrument used in this study is the
      Diagnostic Interview Schedule, Version III (DIS III, 1-10). The main finding is
      of relatively low prevalence of most DSM-III disorders with the exception of
      alcohol abuse and dependence. The rate of alcoholism is astonishingly high among
      elderly Korean males in Los Angeles. The findings are compared with the U.S.
      Epidemiological Catchment Area studies, and with other much larger community
      studies conducted in Korea. A comparison shows that there are no significant
      differences in the prevalence of mental disorders between elderly Koreans in Los
      Angeles and elderly Americans in St. Louis (N = 576) except for the prevalence of
      alcohol abuse and dependence. The lifetime prevalence of DSM-III disorders among
      Koreans in Korea (N = 5100) is generally higher than among elderly Koreans in Los
      Angeles.

PMID- 8149721
TI  - Contrasting a shelter and day center for homeless mentally ill women: four
      patterns of service use.
AB  - This article examines a model of service delivery for homeless mentally ill
      women, a combined day center and shelter program. Using data from participant
      observation and in-depth interviews with 21 clients, four patterns of day center
      and shelter use are delineated. Overall, few women from the day center make the
      transition to the shelter, and then to permanent housing and mental health
      stability. In the absence of a comprehensive public mental health system and low
      income housing, however, many more women benefit from periodic use of the shelter
      as respite from the streets and from daily support services provided by the day
      center.

PMID- 8149722
TI  - Posttraumatic stress disorder in persons with developmental disabilities.
AB  - Persons with developmental disabilities are more frequently abused physically,
      emotionally and sexually than nondisabled persons (Ammerman, Van-Hasselt, Herson,
      McGonigle, & Lubetsky, 1989; Sobsey, Gray, Pyper, & Reimer-Heck, 1991). Persons
      with developmental disabilities are susceptible to the full range of psychiatric
      disorders (Szymanski, Madow, Mallory, Menolascino, & Pace, 1991). There has been
      no comprehensive study of posttraumatic stress disorder (PTSD) in this population
      (Hudson & Pilek, 1990), a recent textbook of mental health and mental retardation
      does not contain index listings on this condition (Fletcher & Menolascino, 1989),
      and psychometric tests currently proposed for use with the retarded do not
      examine for this condition (Aman, Watson, Singh, Turbott, & Wilsher, 1986). In
      this preliminary study, descriptive data from 51 persons with developmental
      disabilities who met DSM-IIIR criteria for posttraumatic stress disorder are
      reported. The majority of cases were detected upon routine initial psychiatric
      interview and record review. Demographics, family histories, and comorbid
      psychiatric conditions are described. In this sample all patients who received
      comprehensive recommended treatment improved.

PMID- 8149723
TI  - A new technique for handling sexually abusive calls to telephone crisis lines.
AB  - Sexually abusive calls interfere with the legitimate functions of crisis lines
      and have detrimental effects on crisis line workers. This paper describes a new
      approach to responding to such calls in a way that meets the needs of the crisis
      line and encourages callers to seek therapeutic treatment for their problem. The
      proposed response is based on principles of covert conditioning and Ericksonian
      suggestions. A script of the response is presented along with a description of
      the rationale and suggested precautions for use with callers.

PMID- 8149724
TI  - Areas of skill training for persons with mental illness and substance use
      disorders: building skills for successful community living.

PMID- 8149725
TI  - The HIV mental health spectrum.
AB  - The growing mental health needs that are related to HIV are immense and diverse.
      The HIV mental health spectrum is a model that identifies and characterizes
      populations in need of HIV-related services which can be offered by Community
      Mental Health Centers. The spectrum describes the specialized service
      requirements for each of these populations, the challenges in providing these
      services, and staff training needs. The authors propose this as a useful model
      for clinicians, researchers, educators, and administrators in planning to meet
      the needs of this expanding epidemic.

PMID- 8149726
TI  - The use of clozapine in borderline-intellectual-functioning and mentally retarded
      schizophrenic patients.
AB  - The effect of clozapine, an atypical antipsychotic medication, in five patients
      with treatment-resistant schizophrenia or schizoaffective disorder and borderline
      intellectual functioning or mental retardation (MR) was studied. Four of the five
      patients responded favorably to clozapine with few side effects. Progressive
      improvement in psychopathology, social functioning, and ability to participate in
      daily activities were noted.

PMID- 8149727
TI  - Correlations over time between dysphoric mood and symptomatology in
      schizophrenia.
AB  - Monthly assessments of depression, anxiety, and positive and negative symptoms of
      schizophrenia were performed on 52 schizophrenic patients over periods ranging
      from 12 to 29 months. Data were analyzed to assess the extent to which symptoms
      of dysphoria (anxiety and depression) were more strongly related to negative or
      positive symptoms of schizophrenia. Consistent with past research using
      comparisons across subjects, the current longitudinal data show that there is a
      more consistent relationship between dysphoria and positive rather than negative
      symptoms.

PMID- 8149728
TI  - Higher morbidity risk for schizophrenia in males: fact or fiction?
AB  - Male to female ratios in published annual incidence rates for schizophrenia range
      from 0.70 to 3.47. These variations between studies are attributed to differences
      in sampling, diagnostic criteria, design characteristics, and methods of
      calculation, which limit the quality of the studies. In an effort to overcome
      these shortcomings, we collected a comprehensive sample of 392 consecutive first
      admissions with a diagnosis of schizophrenia or a similar disorder out of a
      population of 1.5 million in a central region of western Germany. In this large
      representative sample, no significant gender differences in the incidence of
      schizophrenia could be detected regardless of different diagnostic definitions.

PMID- 8149729
TI  - The effects of psychiatric and psychosocial interviews on children.
AB  - To test child and parent reactions to direct interviewing, a survey was
      administered to parents and children who had been directly interviewed as part of
      two family alcoholism studies. Subjects had been asked about possible
      psychopathology in the children and about psychosocial stressors that the
      children may have experienced. For this study, parents and children were asked if
      the children had been upset by the experience or affected in any negative way.
      The results show a positive response from both parents and children to all
      aspects of the interview. There were no serious negative effects. Many parents
      and children enjoyed the interview, and none of the families indicated that they
      would not continue to participate in the study because of the questions asked of
      the children.

PMID- 8149730
TI  - Assessment of DSM-III personality structure in a general-population survey.
AB  - The object of this study is to assess the internal validity of DSM-III
      personality constructs and to explore whether the constituent elements are better
      explained by an alternate internally coherent classification. A two-stage
      stratified random sample of subjects identified at the Baltimore site of the
      Epidemiologic Catchment Area (ECA) program were examined by psychiatrists for DSM
      III personality attributes using a semistructured instrument. Dichotomous factor
      analysis was used in the confirmatory mode to test whether a single factor
      explained each of the 11 DSM-III personality disorders. This approach rejected a
      single explanatory factor for all but compulsive personality disorder.
      Exploratory factor analysis showed that these DSM-III personality features are
      parsimoniously described by a five-factor model. These factors are warmth,
      animation, timidity, trust, and scrupulousness.

PMID- 8149731
TI  - Social variables and suicide in the population of Genoa, Italy.
AB  - A study of the relationship between sociodemographic conditions and suicidal risk
      was conducted on 377 cases of suicide committed in Genoa between 1985 and 1988.
      We used random subjects among Genoa residents as a control group. Data obtained
      were analyzed by means of an unconditional logistic regression model. The most
      interesting result of the study is the considerable suicide risk found among
      unmarried people.

PMID- 8149732
TI  - Clinical evaluation of 14 patients with the Charles Bonnet syndrome (isolated
      visual hallucinations).
AB  - A group of 14 patients with isolated visual hallucinations who met the criteria
      proposed by Gold and Rabins for Charles Bonnet syndrome (with the exception of
      the criterion "hallucinations are stereotyped") underwent psychiatric,
      neurologic, and ophthalmologic tests. Additional common characteristics of the
      hallucinations included the absence of personal meaning of the content of the
      hallucinations and the disappearance of the hallucinations when the patients
      closed their eyes. There was no evidence for a relationship of the syndrome to
      psychiatric disorders. In the majority of cases, ocular pathology and neurologic
      disturbances were diagnosed. There was also evidence that most patients were
      suffering from social isolation. From these data it is concluded that a
      combination of factors is probably responsible for the Charles Bonnet syndrome.

PMID- 8149733
TI  - Life events and the 1-year prevalence of major depressive episode, generalized
      anxiety disorder, and panic disorder in a community sample.
AB  - A community survey was conducted in Edmonton, Alberta, Canada, in which 3,070
      respondents completed the Diagnostic Interview Schedule (DIS) and the Life Events
      Scale (LES) of Paykel. During the year before the interview, there were 222, 234,
      and 38 cases of major depressive episode (MDE), generalized anxiety disorder
      (GAD), and panic disorder (PD), respectively, where individuals may have had more
      than one disorder. It was not possible to time the onset of the disorder relative
      to the occurrence of life events, and so correlations, no casual relationships,
      were examined. The LES score showed an increasing trend across disorder
      categories defined as follows: MDE and GAD both absent; MDE absent and GAD
      present; MDE present and GAD absent; and MDE and GAD both present. A similar
      trend was observed for most of the LES subscales studied, but only in the case of
      events classified as "entrance," "undesirable," and "marital" was there
      statistical significance. The results suggest that stressful life events are
      correlated with both MDE and GAD, that individuals with MDE only tend to have a
      greater burden of stressful events and comorbid disorders than persons with GAD
      only, and that the presence of both disorders is associated with an even greater
      level of stress and number of comorbid disorders. The similar patterns across LES
      subscales suggest that MDE and GAD are not related to specific types of live
      events, at least not those covered by the LES questionnaire.

PMID- 8149734
TI  - Clozapine's effect on negative symptoms in treatment-refractory schizophrenics.
AB  - Clozapine has proven to be more effective than typical antipsychotics in
      treatment-refractory schizophrenic patients, and some evidence suggests that it
      may be particularly useful in treating the negative symptoms of schizophrenia.
      However, it is unclear whether this observation reflects improvement in "primary"
      or "secondary" negative symptoms. We hypothesized that a portion of clozapine's
      effect on negative symptoms would be related to an improvement in positive
      (psychotic and disorganization) symptoms, a decrease in extrapyramidal side
      effects (EPSE), and/or a decrease in depressive symptoms. The remainder of its
      effect would be related to a direct effect on the neural circuits or pathologic
      processes responsible for the negative symptoms. Twenty-nine treatment-refractory
      schizophrenics treated with clozapine for 6 weeks were studied. The core negative
      symptoms measured by the Scale for the Assessment of Negative Symptoms ([SANS]
      affective flattening, anhedonia/asociality, avolition/apathy, and alogia) all
      improved with clozapine treatment. Overall, there was a 31% improvement in
      negative symptoms, a 32% improvement in psychotic symptoms, and a 35% improvement
      in disorganization. The improvement in negative symptoms was correlated with
      improvement in disorganization, but not with improvement in psychotic symptoms,
      depression, or drug-induced EPSE. Although there was a correlation between
      improvement in negative symptoms and improvement in disorganization, there was a
      suggestion that the two are changing in parallel, but are independent of each
      other. It appears that at least a portion of clozapine's effect on core negative
      symptoms is mediated through a direct effect on the underlying pathophysiology of
      schizophrenia associated with negative symptoms.

PMID- 8149735
TI  - Choking phobia: a review of the literature.
AB  - Choking phobia is characterized by fear and avoidance of swallowing food, fluids,
      or pills. Most individuals with this phobia suddenly acquire their fear after an
      episode of choking on food. Fear of choking appears to occur somewhat more often
      in females than in males, and has a variable age of onset ranging from childhood
      to old age. Its prevalence is unknown. Choking phobia appears responsive to
      antipanic medication and to certain cognitive and behavioral therapies.

PMID- 8149736
TI  - Screening mammography: the Mount Sinai BreastCheck experience.
AB  - Early detection can result in a decrease in the death rate from breast cancer.
      Screening mammography is the most important modality available to discover early
      so-called "minimal" cancer. In an effort to make screening mammography more
      available to the women of north central Connecticut, Mount Sinai Hospital, a
      community based, university-affiliated hospital initiated a screening program
      five years ago. During the four-year interval on which we are reporting, we have
      screened almost 15,000 women using a mobile van. Seventy-seven cancers were
      discovered in this screened population, with a detection rate of five cancers per
      1,000. Our biopsy rate was 1.5% with a positive predictive value of 34%. Sixty
      one percent of the tumors discovered were so-called "minimal" cancers and only 12
      of the 77 patients had positive lymph nodes.

PMID- 8149737
TI  - The right to die--an individual's perspective.

PMID- 8149739
TI  - "Inappropriate treatment or inappropriate prevention?".

PMID- 8149738
TI  - Outcome measures, quality and health care reform.

PMID- 8149740
TI  - American medical education: no one does it better.

PMID- 8149741
TI  - Comparison of the proteoglycanolytic activities of human leukocyte elastase and
      human cathepsin G in vitro and in vivo.
AB  - In this study, we evaluated the in vitro and in vivo potency of human leukocyte
      elastase (HLE) and human cathepsin G (HCG) as proteoglycanases. In vitro
      evaluation was done using bovine nasal septum aggrecan and aggrecan/hyaluronan
      aggregate as substrates. Enzyme activity was assessed by the ability of the
      proteinases to abrogate the ability of aggrecan to aggregate with hyaluronan. In
      vivo activity of the proteinases was tested by injecting purified HLE and HCG
      intra-articularly into rabbit stifle joints and quantifying the levels of
      proteoglycan released into synovial fluids. On a molar basis, HCG was at least
      tenfold more potent than HLE as a proteoglycanase in vitro. Moreover, HCG was
      twofold more potent as a proteoglycanase in vivo. In contrast, HLE hydrolyzed
      elastin approximately 22-fold faster than HCG, but was only slightly more rapid
      than HCG when [3H]-transferrin was used as substrate. These data indicate that
      HCG is more potent than HLE as a proteoglycanase both in vitro and in vivo. Thus,
      HCG could be more important in the pathogenesis of rheumatoid arthritis than
      previously suspected.

PMID- 8149742
TI  - A variant form of laminin is responsible for the neurite outgrowth-promoting
      activity in conditioned medium from a squamous carcinoma cell line.
AB  - We examined the effects of conditioned medium (CM) obtained from a squamous
      carcinoma cell line, termed SAS, on chick sympathetic neuritic outgrowth. Neurons
      grown on a substratum coated with CM extended their neurites. Antisera raised
      against human laminin and mouse EHS laminin immunoprecipitated the neurite
      outgrowth-promoting factor in CM. The most purified fraction of CM contained a
      740-kDa protein which reacted with the anti-laminin sera and was composed of
      three polypeptides of 330 kDa, 215 kDa and 195 kDa. The 215-kDa and 195-kDa
      polypeptides, but not the 330-kDa polypeptide were shown to be antigenically
      related to mouse laminin and human laminin by immunoblotting. The presence of
      merosin M chain in SAS cells was ruled out by using the method of reverse
      transcription polymerase chain reaction (RT-PCR). These results suggest that the
      740-kDa protein is a laminin variant having a novel heavy chain of 330 kDa and is
      responsible for neurite outgrowth-promoting activity in CM.

PMID- 8149743
TI  - Development of functional specializations within the maturing rabbit flexor
      digitorum profundus tendon.
AB  - Along its length, the rabbit flexor digitorum profundus (FDP) tendon exhibits two
      functionally specialized regions: classical tendon (CT) and fibrocartilage (FC).
      We examined their development in rabbits, ranging in age from newborn to nine
      months postnatal, using a combination of light microscopic, immunohistochemical
      and biochemical techniques. There is little histodifferentiation in newborn
      tendon. Both regions are composed of thin collagenous fibers, numerous fibroblast
      like cells and a low molecular weight dermatan-sulfate proteoglycan. Regional
      specialization has begun by two-weeks postnatal and by three-months postnatal, FC
      regions have been transformed into a true fibrocartilage characterized by a
      complex collagenous and elastic fiber network, numerous chondrocytes and a matrix
      rich in a high molecular weight predominantly chondroitin-sulfate proteoglycan
      and type II collagen. These features are elaborated between three and nine-months
      postnatal. CT regions undergo little substantial change during growth and
      maturation. The rabbit is born altricial and incapable of adult patterns of
      locomotion. We propose that the developmental expression of functional
      specializations within the FDP tendon is closely linked with the onset of
      different physical demands arising from the adoption of adult patterns of
      locomotion.

PMID- 8149744
TI  - Adhesion promoting property of laminin from normal tissue and from a tumorigenic
      cell line.
AB  - The cell adhesion promoting activity of laminin isolated from normal human
      placenta was compared with that isolated from mouse EHS tumor and from the
      cultures of a mouse epithelial cell line B82 and its tumorigenic derivative,
      B82HT. The adhesion promoting properties of commercial merosin isolated from
      placenta was also compared with the above preparations using the human
      fibrosarcoma HT1080 cells. Percent attachment was defined as (radioactivity
      extracted from attached cells)/(radioactivity in cells added to assay) x 100.
      HT1080 cells adhered more efficiently on laminin (0.5 micrograms/well), isolated
      from the B82 rather than B82HT cell conditioned medium, (82% vs 64%). Percent
      attachment of HT1080 cells on isolated native placental laminin or commercial
      merosin was significantly higher compared to laminin from the EHS tumor (at 0.75
      micrograms/well, 69%, 73% and 20% respectively). In parallel experiments the
      steady-state levels of mRNAs for subunits A, M, B1 and B2 in cultures of B82 and
      B82HT cells were determined. The ratio of mRNA for the laminin subunits in B82
      and B82HT cells was 1:0.9 for the A chain, 1:0.6 for the M chain, 1:0.4 for the
      B1 chain, and 1:0.3 for the B2 chain. Protein studies indicated that the M
      subunit is absent in laminin preparations from the EHS tumor whereas it is
      abundant in the laminin from placenta and in commercial merosin. Laminin isolated
      from B82 cells contains a higher proportion of the M subunit compared to that
      from B82HT cells. The data suggest that there are functional differences between
      the laminin found in normal tissue and that present in a solid tumor. Functional
      differences were noted between the laminins synthesized by the B82 cell line and
      its tumorigenic counterpart, B82HT. These differences may result from the lack of
      gene expression for the laminin subunit M by the EHS tumor and by the lower
      degree of gene expression for this subunit by B82HT cells. The possibility that
      the laminin synthesized by the tumorigenic cell line may be structurally
      different from that synthesized by the B82 cells should also be considered.

PMID- 8149745
TI  - Stress-sharing between the fluid and solid components of articular cartilage
      under varying rates of compression.
AB  - This paper investigates the factors affecting the mechanical behavior of the
      articular cartilage matrix with special emphasis on the effect of compressive
      strain-rate on the short and long term responses of the fluid and the solid
      components. The relationships expressed in the general theory of one-dimensional
      consolidation are generalized to account for strain-rate in the deformation
      process with the result that the stiffness due to the fluid and the solid
      components, and a parameter representing the degree of drag, can be calculated
      explicitly.

PMID- 8149746
TI  - A new biomechanical approach to assessing the fragility of the internal elastic
      lamina of the arterial wall.
AB  - Patterns of tearing of the internal elastic lamina induced by controlled tensile
      extension of the arterial wall in the axial direction are similar morphologically
      to those induced in vivo in the anastomosed arteries of experimental
      arteriovenous fistulae. The mural response is modelled with a simple bi-layer
      analogue and it is shown that the internal elastic lamina exhibits a greater
      degree of strain-limiting deformation behavior in the axial direction than the
      medial and adventitial layers. Application of laminate theory indicates that the
      frequency of intimal tearing along the vessel length is directly related to the
      failure strength of the intimal layer.

PMID- 8149747
TI  - Mechanisms of interaction of albumin with arterial elastin.
AB  - Binding of proteins, lipoproteins and calcium salts to arterial elastin occurs
      with age and in disease. In order to clarify the mechanisms of interaction we
      investigated the binding of native and charge-modified albumins to elastin
      isolated by alkali extraction of the porcine aorta. Fluorescence microscopy was
      used to quantify the distribution of lissamine-rhodamine labelled albumins in
      native and charge-modified elastins under different solution conditions. For
      native albumin uptake was approximately twice as high on the intimal and
      adventitial sides as in the mid media. The distribution of anionic albumin was
      very similar, but methylation either of the albumin or the elastin greatly
      reduced the transmural variation. The uptake of methylated albumin was
      approximately three-fold greater than the native albumin. The uptake of the
      native albumin was reduced preferentially in the intimal region in the presence
      of calcium and only the charge-modified proteins were able to penetrate the
      intralamellar space. These observations demonstrated the importance of
      hydrophobic interactions in albumin binding.

PMID- 8149748
TI  - Specific beta estradiol binding in cartilage and serum from young mice and rats
      is age dependent.
AB  - Various studies have shown a direct effect of beta estradiol on cartilage and
      bone. Such effects point to the possibility that specific receptors to estradiol
      exist in the growth plate cartilage as well as in bone. 3H-estradiol specific
      binding (EB) was therefore investigated in the supernatant of cartilage
      homogenates from the epiphyses and ribs of young growing mice and rats. High
      levels of EB were observed in the cytosol fraction of cartilage homogenates in
      the late fetal stage and in young rats and mice. The EB levels decreased
      gradually from late fetal stage up to 14 days of age in both groups of animals
      independent of their sex. Nuclear binding of 3H estradiol was also demonstrated
      by autoradiography in the chondrocytes of proliferating and hypertrophic zones.
      Estradiol binding was inhibited by high doses of unlabelled beta-estradiol, but
      not by alpha estradiol. Binding was also inhibited by tamoxifen and DES but not
      by testosterone. High levels of estradiol binding (EBS) were also observed in
      serum from young animals, but not in animals 2 months of age or older. Study of
      estradiol binding in cartilage and in serum of rats of the same age showed a
      significant difference in estradiol binding between these two systems. The
      difference in estradiol binding between serum and cartilage was seen in the
      response to inhibitors, Scatchard analysis, and temperature dependence. The
      results of our study imply that there are specific receptors for 17 beta
      estradiol in growth plate cartilage; they originate from chondrocytes, and their
      amount decreases with age. The effects of estradiol on endochondral bone growth
      seems therefore to be receptor mediated.

PMID- 8149749
TI  - The rates of cleavage of insoluble and soluble collagens by tissue collagenases.
AB  - The cleavage rates of insoluble and acid-soluble bovine collagens by tissue
      collagenases from the cultures of C3H mouse mammary adenocarcinoma and from human
      rheumatoid synovial fibroblasts at 37 degrees C were compared by measuring dansyl
      (Dns)-IIe and Dns-Leu, amino-terminal residues at the cleaved sites after
      dansylation. The kinetic parameters, Kcat and Km, defined functionally, were as
      follows: for insoluble Achilles tendon collagen, Km values were 0.89 and 0.83
      microM; Kcat/Km 39.2 and 317 microM-1 h-1. For acid-soluble skin collagen the
      values were 0.83 and 0.82 microM; 44.6 and 354 microM, respectively. The
      supernatants from the insoluble and acid-soluble collagens contained 28% and 92%
      of total Dns-IIe and 1.3% and 43% of total Hyp, respectively. Results showed that
      both tissue collagenases cleaved insoluble collagen almost as rapidly as they did
      reconstituted collagen fibrils. The cleavage of collagen was proportional to
      enzyme concentration. The presence of Dns-IIe and Dns-Leu in the supernatant
      arises from a second cleavage of the collagen molecule.

PMID- 8149750
TI  - [Prof. Frantisek Herles, the founder of Czech electrocardiology and
      cardiorespiratory pathophysiology].

PMID- 8149751
TI  - [Acute venous thrombosis (deep venous thrombosis)].

PMID- 8149752
TI  - Ten years of a heart transplant programme in Prague.

PMID- 8149753
TI  - Lipid parameters in blood of vegetarians.
AB  - Lipid parameters (cholesterol CH, HDL-, LDL-cholesterol, triacylglycerols TG,
      atherogenic index AI) were estimated in four age groups of vegetarians, 82 males
      and 80 females, aged 15 to 60 years. The period of consumption of vegetarian food
      was 1.4 to 1.9 years for adolescents (15-18 years old) or 2.4 to 5.4 years for
      adults (age groups 19-29 years, 30-39 years and 40-60 years). Lacto-vegetarians
      constituted one half of females and one third of males. Vitamin C content, lipid
      peroxidation levels (conjugated dienes, CD) and the activities of catalase (CAT)
      and glutathione peroxidase (GSH-Px) were estimated in the oldest age group of
      males and females. Low levels of TG and glutathione peroxidase (GSH-Px) were
      estimated in the oldest age group of males and females. Low levels of TG and CH
      (in the lower half of the reference range), low calculated values of LDL-CH and
      AI, as well as values of HDL-CH in the upper region of the standard risk zone or
      over 1.4 mmol/l (reduced risk level) in males and females of all age groups are
      the positive factors of vegetarian nutrition in prevention of atherosclerosis.
      High levels of vitamin C in blood, absence of obesity and low blood pressure
      should be mentioned here as additional positive factors as well. When considered
      as a single isolated factor, the nearly significantly elevated values of CD
      (linked to increased intake of unsaturated fatty acids) could be a negative
      factor of vegetarian nutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149754
TI  - Recent atrial fibrillation in acute myocardial infarction: a sign of
      pericarditis.
AB  - The association between recent atrial fibrillation during the course of acute
      myocardial infarction and pericarditis or pericardial effusion occurring during
      the hospital phase of myocardial infarction was studied by means of serial
      echocardiographic examinations in 192 patients presenting with their first
      myocardial infarction. Clinical pericarditis was found in 8%, echocardiographic
      effusion in 43%, and atrial fibrillation in 5% of all patients. Atrial
      fibrillation was present in only 2% of patients without pericardial effusion
      compared to 15% of patients with more than minimal effusion (p = 0.0094). Thus,
      pericarditis might play a role in the development of recent atrial fibrillation
      during the course of myocardial infarction. Recent atrial fibrillation may be a
      sign of pericardial effusion which may be otherwise silent.

PMID- 8149755
TI  - [Transseptal approach to the left atrium].
AB  - The authors present their first experience with trans-septal access to the left
      atrium, employed in 22 procedures of mitral valve surgery and in 4 myxoma
      extirpations. The majority of cases were re-operations or combined procedures,
      performed most often in connection with tricuspid valve annuloplasty. There were
      two deaths (7.6%), serious arrhythmias or signs of an intra-atrial shunt were not
      seen in any of the patients undergoing surgery. Trans-septal access allows
      thorough orientation in the left atrium, and the authors find it useful
      especially in re-operations or combined procedures.

PMID- 8149756
TI  - [History of heart transplantation].
AB  - The article examines the history of heart transplantation in experiment and in
      clinical practice. The part focusing on experimental transplantation covers the
      period from the very first attempts in 1905 up to the introduction of the current
      technique. The second part provides an outline of the history of transplantation
      in clinical practice including immunosuppressive therapy and rejection control.
      The first heart transplantation in the Czech Republic was performed in 1984.

PMID- 8149757
TI  - [Indications for heart transplantation].
AB  - Heart transplantation may have a considerable impact on the fate of the patient
      in the end stage of heart failure. A successful procedure requires the existence
      of a sophisticated programme combining the expertise of top departments of
      cardiology and cardiac surgery working in conjunction with the transplant centre
      directly responsible for removing the organ. One of the factors playing an
      important role in a favourable outcome is the correct indication for the
      procedure. The information on patient selection and criteria for the heart donor,
      presented in this paper, become increasingly important even for the practitioner
      in cardiology referring their patients to specialized departments. The paper also
      offers background information on the heart transplant programme in the Czech
      Republic suggesting the need for expanding the availability of the therapeutic
      method in this country.

PMID- 8149758
TI  - [Surgical problems in heart transplantation].
AB  - Today, heart transplantation is a generally recognized method for managing an
      otherwise uncontrollable heart failure. The surgical technique of transplantation
      has become standardized in recent years. There are no substantial differences in
      postoperative care and the rate of surgical complications between a heart
      transplant recipient and a patient undergoing routine cardiac surgery. The only
      problem to be handled is the recipient's elevated pulmonary resistance. Late
      complications are caused by infection related to immunosuppression and/or
      antirejection therapy.

PMID- 8149759
TI  - [Noninvasive diagnosis of myocardial rejection using echocardiography].
AB  - The potential of echocardiography in evaluating myocardial rejection was
      determined in 56 patients (8 females) following orthotopic heart transplantation.
      The patients' average age was 42.3 (range 18-67) years. Endomyocardial biopsy was
      used as the reference method. The study included a total of 254 results of
      biopsy: 137 specimens were free of any signs of rejection while 51 showed
      incipient rejection and mild rejection was found in 54 specimens. Moderate
      rejection was detected in 12 specimens; severe rejection was not present in any
      case. Echocardiography was used to determine ventricular size, wall thickness,
      left ventricular function, pericardial effusion, mitral and tricuspid flow and
      isovolumic relaxation time. Rejection has been found to be associated with
      ventricular wall thickening; the appearance of or an increase in pericardial
      effusion seems to be a relatively specific feature (a very low-sensitivity marker
      though); change in isovolumic relaxation time is believed to be the most
      sensitive marker. No relation between rejection and mitral and tricuspid flow was
      demonstrated. Echocardiography may alert the cardiologist to a rejection episode;
      isovolumic relaxation time and its alterations are the most informative features
      in this respect. The method may help postpone the intervals of biopsy which,
      however, must be performed on the slightest suspicion of rejection. Still, it
      cannot be regarded as a replacement for endomyocardial biopsy at the moment.

PMID- 8149760
TI  - [Standardization in the evaluation of acute rejection in heart transplantation].
AB  - The author presents a review of acute rejection classifications from the point of
      view of histology. She examines the relationship between conventional and
      cyclosporin immunosuppression and the differences in clinical practice and
      morphology. The article includes Stanford, Texas, Hannover and Brigham's
      classifications. Because of the inconsistent use of classifications in
      endomyocardial biopsy evaluation, the Society for Heart Transplantation has
      developed a standard biopsy classification system also presented in the article.

PMID- 8149761
TI  - [The patient after heart transplantation].
AB  - The data of the first 100 patients undergoing heart transplantation in the period
      between January 1984 and May 1993 were analyzed. Of this group, 57 patients are
      alive. Out of the total of 43 deaths, 14 patients died from graft failure within
      the first postoperative days, 6 died from surgical complications, 11 from
      infection, 10 deaths were due to accelerated coronary atherosclerosis, and 2
      patients died from tumours. Early mortality rates (within 30 days since surgery)
      were 37% and 17% in patients operated on between 1984-88 and between 1989-93,
      respectively. The health condition of heart transplant recipients is affected by
      side effects of immunosuppressive therapy. Forty per cent of patients re-develop
      systemic hypertension within the first post-transplantation year. Five years
      after transplantation, hypertension is detected in 60% of patients. Elevated
      serum creatinine levels are present in 70% of patients by the end of the first
      post-transplantation year. In the ensuing period, there is no progression in
      renal function impairment, which does not require cyclosporin withdrawal and is
      not associated with the development of hypertension. In the first post
      transplantation year, 45% of patients are markedly obese. All patients with
      overweight and obesity show markedly raised levels of serum cholesterol. Another
      undesirable effect (mainly due to corticosteroid therapy) is the development of
      ulcers in 16% of patients. Heart transplantation has become an established method
      at the Institute for Clinical and Experimental Medicine in Prague. Despite the
      above pitfalls, heart transplantation substantially prolongs the life of patients
      and dramatically alters the quality of their life.

PMID- 8149762
TI  - [Infectious complications in patients after heart transplantation].
AB  - The incidence of infectious complications was monitored in a group of the first
      100 patients undergoing orthotopic heart transplantation at the Institute for
      Clinical and Experimental Medicine from January 1984 through May 1993. The
      definition of an infectious complication was a clinically manifest infection
      requiring treatment. Cytomegalovirus infection and Epstein-Barr virus infection
      were evaluated by the development of antibody against IgM. A total of 168
      infectious complications were detected in 80 patients. The infectious
      complications were fatal in 11 patients; hence, infections were implicated in 26%
      of all deaths following heart transplantation. The spectrum of infections
      markedly varies depending on the interval since the procedure. The most frequent
      infections within the 30 postoperative days are bacterial (often nosocomial)
      infections. In the later period (30 days onward), viral infections account for
      72% of cases. Of the rarer types of infections, the pulmonary form of
      aspergillosis was identified in 3 cases, nocardiosis and legionellosis in one
      case each. Infectious complications were the main cause of deaths in the period
      of 1 to 4 months post-transplantation, and the spectrum and rate of complications
      were not different from data reported by other centres.

PMID- 8149763
TI  - [Coronary disease in patients after heart transplantation].
AB  - Coronary artery lesions are evaluated in a group of 43 patients surviving for
      more than 3 months after heart transplantation. An angiographic finding was
      obtained from 35 patients, autopsy findings were available in eight cases.
      Angiography demonstrated coronary artery lesions in 12 out of the 35 patients
      whereas autopsy findings were positive in five out of the eight post mortem
      examinations. Overall, lesions were found in 40% of patients at a mean follow-up
      interval of 3.5 years. While the finding of a coronary artery lesion was not
      related to the classic risk factors for atherosclerosis, an association to a
      previous cytomegalovirus or Epstein-Barr virus infection was demonstrated. The
      data suggest that infection caused by the two above viruses is an important
      factor in the development of vascular lesions in the heart transplant.

PMID- 8149764
TI  - [New developments in emergency resuscitation].
AB  - Cardiopulmonary resuscitation at present cannot, and in the future will not,
      constitute solely a uniform technique. Specific algorithms for sudden primary
      cardiac arrest have been developed which are to be further refined, and there is
      no reason why our country should lag behind the advanced nations in this respect.
      A key role in the outcome is played by other important factors such as
      instruction and training of the population enabling it to initiate basic life
      support, short time intervals from cardiac arrest to advanced life support,
      technical standard of the equipment available, expertise of medical emergency
      teams and physicians, prophylaxis of multiorgan dysfunction in the post
      resuscitation period, and psychosomatic rehabilitation. All the above aspects
      make up a complex issue we have to do our best to tackle systematically and as
      soon as possible.

PMID- 8149765
TI  - A thrombus in the right pulmonary artery and its follow-up using transoesophageal
      echocardiography.
AB  - Using transoesophageal echocardiography, the authors documented development of a
      right pulmonary artery thrombus in a patient with pulmonary hypertension due to
      chronic obstructive lung disease. This case confirms the potential of
      transoesophageal echocardiography in diagnosing pulmonary artery diseases.

PMID- 8149766
TI  - "Cardioprotection"--not all calcium antagonists are created equal.

PMID- 8149767
TI  - Ignorance and the process of learning and discovery in medicine.

PMID- 8149768
TI  - Generalizing from clinical trials.
AB  - Although randomized controlled clinical trials have become the "gold standard"
      for evaluating new treatments, only a small subset of the population considered
      for treatment participate in randomized clinical trials. To what extent is it
      reasonable to generalize beyond the boundaries of a specific clinical trial? This
      paper argues that several pieces of information are necessary to determine the
      extent of extrapolation or generalization warranted in a specific clinical trial.
      The necessary items of information are derived from basic science laboratory
      studies; animal studies; genetic studies (where applicable); observational,
      clinical, and epidemiological studies; and other randomized clinical trials in
      similar settings or with similar treatments. An example from the field of
      cholesterol reduction is presented.

PMID- 8149769
TI  - Generalizing the results of randomized clinical trials.
AB  - Many scientific and statistical issues are involved in generalizing the results
      of randomized clinical trials. This paper examines the issues of heterogeneity of
      risk and heterogeneity of effect, as well as quantitative vs. qualitative
      heterogeneity. Generalization of quantitative results to populations at different
      risk is shown to be problematic, independent of any other considerations. Issues
      of heterogeneity as they relate to target population and choice of therapy are
      discussed. A few proposals are offered regarding the design and report of trials.

PMID- 8149770
TI  - Features of the nutrient database and analysis system for the Modification of
      Diet in Renal Disease Study.
AB  - This article describes the features of the nutrient database and analysis system
      developed for the Modification of Diet in Renal Disease (MDRD) Study and outlines
      the development process itself, an example of tailoring a database and analysis
      system for a complex, long-term clinical trial. The MDRD Study was a 15-center
      trial for men and women aged 18 to 70 years with chronic renal disease who were
      not on dialysis and who had not had a kidney transplant. The effects of three
      levels of protein and phosphorus intake and two levels of blood pressure
      management were assessed on the rate of decline in kidney function. This paper
      describes the development, structure, contents, and application of the nutrient
      database and analysis system that was used to enter, analyze, and report the MDRD
      Study dietary data.

PMID- 8149771
TI  - Design of the training levels comparison trial.
AB  - The Training Levels Comparison (TLC) trial was a grant-supported, multicenter,
      randomized, controlled clinical trial designed to determine whether cardiac
      rehabilitation patients would benefit from supervised exercise for a prolonged
      period (2 years) and whether subjecting patients to a more vigorous exercise
      program than currently recommended would provide additional cardiac benefit. If
      high-intensity exercise does not enhance the cardiac benefit, then physical
      activity should be limited to low-intensity levels that are safer, easier to
      implement and more adaptable to a greater number of patients. Patients were
      randomly assigned to either a low-intensity or high-intensity training program.
      All patients were to attend three 1-hour supervised exercise sessions per week
      for a period of 2 years. Attendance at exercise sessions and adherence to
      assigned treatments were monitored throughout the study. Patients were evaluated
      for outcome measures at 3, 6, 12, and 24 months. This paper reports the study
      design and methodology for the TLC trial, and should be useful in providing
      methodologies to facilitate comparison of data from other studies with different
      levels of exercise as an intervention.

PMID- 8149772
TI  - From clinical trials to clinical practice: generalizing from participant to
      patient.
AB  - This paper uses the report of the Lipid Research Clinics Coronary Primary
      Prevention Trial as an example of how clinicians apply the results of clinical
      trials to their practice. Clinical trials influence practice primarily to the
      extent that they eventually become incorporated into the generally accepted
      standard of medical care. To a lesser extent, physicians are influenced by their
      own interpretation of clinical trial results. Since physicians usually do not
      have the leisure or the technical expertise to evaluate primary data critically,
      their conclusions are heavily influenced by the authors' sometimes overoptimistic
      interpretation of the results. Therefore, practicing clinicians often
      overestimate the benefits of a therapy and generalize the results of a trial too
      broadly. Ideally, physicians should base treatment decisions on their knowledge
      of the pathophysiology of the disease, the mechanism of action of the proposed
      treatment, and the clinical characteristics of the individual patient while
      informing their decision with a critical understanding of the results of relevant
      trials.

PMID- 8149773
TI  - A note on sample size determination for comparison of small probabilities.

PMID- 8149774
TI  - Supervision in tribal and state child welfare agencies: professionalization,
      responsibilities, training needs, and satisfaction.
AB  - Although tribal child welfare and family services have expanded substantially
      since the enactment of the Indian Child Welfare Act of 1978, little is known
      about tribal child welfare services or their personnel. This exploratory study
      compared supervisors from 11 tribal child welfare agencies and one state child
      welfare agency. Tribal and state supervisors reported similar levels of
      supervisory professionalization and satisfaction, but they differed in their
      ethnicity, their supervisory tasks, and their training needs. The results were
      interpreted from a systems perspective of ethnic-sensitive agency practice.

PMID- 8149775
TI  - Helping early adolescents tell: a guided exercise for trauma-focused sexual abuse
      treatment groups.
AB  - This article discusses the telling of the personal stories of sexual abuse within
      the context of trauma-focused group therapy for early adolescent girls. It
      examines the general benefits of group therapy for early adolescents, and
      describes the trauma-focused structured group therapy model. It also includes a
      guided exercise that facilitates the telling of the stories by the girls, offers
      cues to the therapists about each girl's unique sexual abuse experience, and
      structures feedback from group members.

PMID- 8149776
TI  - Screening and evaluating abused and neglected children entering protective
      custody.
AB  - Clinical research has documented a variety of problems that abused and neglected
      children present as a result of their having been maltreated. When these children
      enter protective custody, however, they rarely receive systematic screening
      and/or assessment of their current mental health functioning as a part of case
      management. The Screening and Evaluation Project (SEP) is a clinical research
      study examining the range of problems in 167 children entering protective
      custody. Both empirical and theoretical grounds support the importance of early
      screening and evaluation programs for children in these circumstances. Practical
      issues in implementing such programs are also discussed.

PMID- 8149777
TI  - A survey of threats and violence directed against child protection workers in a
      rural state.

PMID- 8149778
TI  - National health care reform, Medicaid, and children in foster care.

PMID- 8149779
TI  - Changes of osteosarcoma treatment over the last two decades.

PMID- 8149780
TI  - Indications, results and complications in connection with free vascularized bone
      transplants for extremity preservation.
AB  - A report is presented on 5 years experience with 33 cases of free vascularized
      bone transplants for extremity preservation. The indications, results and
      complications will be demonstrated. The successful results so far were achieved
      not only by careful indications but by virtue of a strict postoperative treatment
      scheme extending from direct postoperative blood-flow monitoring through the
      raising of a skin flap and angiographic control of anastomosis patency to
      immobilisation/mobilisation and orthotic management.

PMID- 8149781
TI  - A study of the mechanical and biological behavior of bioceramic hip arthroplasty
      followed-up after more than 10 years.
AB  - The authors report the results obtained in three experiments conducted on hip
      arthroplasty with ceramic-ceramic coupling and the evaluation of clinical follow
      ups carried out on cemented bioceramic arthroplasty more than 10 years after
      surgery. A first test consisted in the "in vivo" study of alumina powder injected
      in the joints of four pigs with the purpose of verifying the biocompatibility of
      the compound. A second test involved the experimental evaluation of "in vitro"
      wear of the alumina as compared to other types of coupling, and confirmed the
      very low tendency of wear in alumina. A third spectroscopic study conducted using
      a Raman laser demonstrated the absolute biostability of the surface of bioceramic
      material. A retrospective clinical study was conducted in order to verify
      laboratory data in 83 cemented bioceramic arthroplasties followed-up more than 10
      years after surgery and of which 92% obtained good clinical results.

PMID- 8149782
TI  - Overhead traction in the treatment of congenital dislocation of the hip.
AB  - Long-term results of traction treatment for congenital hip dislocation (CDH)
      performed between 1984 and 1990 are presented. The new traction scheme consists
      of 4 distinctive phases. It is based on gradually changed direction of traction-
      first, from the longitudinal direction to flexion and abduction against the
      hypomochilion. The traction is applied by means of non irritable adhesive tape
      using 1/4-1/5 of the child's body weight. The period of active traction is
      followed by retention period in Hanausek's biomechanical device. The success rate
      of the scheme, in terms of reduction, was 90 per cent. In 31 per cent the Salter
      innominate osteotomy was performed because of residual deformity. In 10 per cent
      of the cases open reduction was necessary.

PMID- 8149783
TI  - The role of magnetic resonance in necrosis of the femoral epiphysis as the
      sequelae of acetabular fracture (preliminary results).
AB  - Eleven patients surgically treated for fracture of the acetabulum were examined
      postoperatively by MRI in order to reveal any signs of necrosis of the femoral
      head at an early stage. The means of osteosynthesis used underwent preliminary
      testing in order to exclude magnetic or thermal phenomena. The study confirmed
      the usefulness of this test in the early diagnosis of this serious complication.
      In 3 cases the presence of the means of osteosynthesis obstructed a correct
      interpretation of the images.

PMID- 8149784
TI  - MR findings in post-traumatic carpal tunnel syndrome.
AB  - Stenosis of the canal secondary to poor consolidation of fractures of the distal
      radial epiphysis is one of the causes of compression on the median nerve of the
      wrist. Other post-traumatic compressive pathologies of the median nerve when
      there are no significant skeletal modifications caused by probable involvement of
      the soft tissues surrounding and within the canal are also described. MR was used
      to study 23 patients affected with the sequelae of fracture of the radial distal
      epiphysis who presented with clinical and electromyographic signs of carpal
      tunnel syndrome, and were submitted to decompressive surgery. MR showed indirect
      signs of compression, such as morphological changes of the median nerve, as well
      as post-traumatic changes in the carpal canal. MR allows for a complete
      anatomical view of the canal structures implicated in causing post-traumatic
      carpal tunnel syndrome.

PMID- 8149785
TI  - Prader-Willi-Labhart syndrome: orthopaedic complications.

PMID- 8149786
TI  - Gout arthropathy: description of an atypical case.
AB  - The authors describe a case of gout localized in the knee, the clinical and
      radiographic signs of which may lead to numerous diagnostic interpretations.
      Other affections with which differential diagnosis is difficult are reported, and
      principal diagnostic tests are described.

PMID- 8149787
TI  - Osteochondroma of the cervical spine. Case report.
AB  - A case of solitary osteochondroma arising from the spinous process of the C7
      vertebra is presented. An early excision of the tumor to avoid complications due
      to cord compression and malignant transformation is suggested.

PMID- 8149788
TI  - A case of perinatal osteoarthritis of the hip complicated by diaphyseal
      osteomyelitis of the femur.

PMID- 8149789
TI  - In memoriam Oscar Scaglietti.

PMID- 8149790
TI  - [The status of postoperative pain treatment from the surgical viewpoint].

PMID- 8149791
TI  - [Legal aspects of postoperative pain treatment].

PMID- 8149792
TI  - [Ovarian cancer--a visceral surgery problem?].

PMID- 8149793
TI  - [Secondary debulking operation in ovarian cancer].

PMID- 8149794
TI  - [Standard of chemotherapy in ovarian cancer].

PMID- 8149795
TI  - [Principles of staging laparotomy in ovarian cancer].

PMID- 8149796
TI  - [To what extent are laparoscopic procedures defensible in oncologic surgery?].
AB  - Successful oncological standard procedures can only be replaced by new methods if
      their value has been proven by long-term results. Laparoscopic tumor resections
      with curative intention have to be considered experimental, especially because
      long-term results are not yet available. These operations require two
      preconditions: 1) the oncological quality of tumor resection must be assessed by
      special methods of pathohistological examinations; and 2) long-term follow-up
      care must be guaranteed. In most cases, these preconditions are only secured
      within clinical trials.

PMID- 8149797
TI  - [Laparoscopic cholecystectomy in morbid obesity. Indications or
      contraindications?].
AB  - In early reports on the experience with laparoscopic cholecystectomy severe
      obesity was considered a contraindication for this procedure. The prospectively
      documented data of 370 consecutive patients undergoing laparoscopic
      cholecystectomy were analysed to investigate, whether this point of view is still
      justified. 35 of these 370 patients were classified as being severely obese (body
      mass-index greater than 33 kg/m2). Median operation time was significantly longer
      in these patients than in the remaining patients (p < 0.05). In selected cases
      the operative technique had to be slightly modified due to extreme abdominal wall
      thickness. Dissection of Calot's triangle was not more difficult than in non
      obese patients. There was no statistically significant difference concerning
      conversion rates between severely obese patients (11.4%) and the other group of
      patients (15.5%). Also, the number of complications was not increased in the
      obese patients. Since the higher complication rate in severely obese patients
      after conventional abdominal surgery is mainly due to the incision, laparoscopic
      cholecystectomy is the preferable procedure to treat symptomatic gallstone
      disease in these patients.

PMID- 8149798
TI  - [Changes in therapy of severe acute pancreatitis].
AB  - Report about the treatment of necrotizing pancreatitis in the years 1988 until
      1991. A rigorous conservative therapy was preferred, so that only 8.6% of the 140
      patients underwent surgery. In 11 cases a continuous venous-venous hemofiltration
      (CVVH) was applied to patients with most serious clinical course and multi-system
      failure. The overall lethality rate of all treated patients was 7.9%. The present
      results show, that, eliminating mediators by hemofiltration, system failure in
      connection with sterile necrosis can be treated with a good success rate.
      Therefore toxic organ failure should no longer be regarded as an imperative
      indication for operation. We recommend strict intensive care including CVVH and
      antibiotical prophylaxis for treatment of sterile necrosis, while surgical
      therapy should only be applied to patients with bacterial contamination of
      pancreatic necrosis.

PMID- 8149799
TI  - [Surgery of locally advanced non-small-cell bronchial cancer after intensive
      preoperative chemo-/radiotherapy].
AB  - From March 1991 to June 1993 50 patients with local advanced NSCLC
      (mediastinoscopy obligatory) have been entered into an ongoing trial with
      preoperative chemotherapy and simultaneous chemo-/radiotherapy, followed by re
      mediastinoscopy and surgery. Clinical response rates after chemotherapy amounted
      to 66.8% after chemo/radiotherapy 77.5%, no severe toxicity was observed. 36
      patients ultimately underwent operation, 29 with a curative, 5 with a palliative
      resection and 2 with an explorative thoracotomy. Pathological complete remission
      rates of the primary tumor were found in 11 (32.3%), R0-resection in 18 (52.9%)
      and R1-resection in 5 (14.7%) cases. Sterilisation rates of mediastinal nodes
      were found in 86.3% of N2 tumors and 66.6% of N3 tumors. Median survival time
      ranged between 21 months for stage III a and 16 months for III b disease. This
      intensive preoperative neoadjuvant treatment is tolerable and effective, the
      requirements for a randomised comparative trial was met.

PMID- 8149800
TI  - [Resection with primary anastomosis in complicated diverticulitis. Risk
      analysis].
AB  - 107 patients operated for complicated diverticulitis 1988 until 1993 were
      analysed retrospectively regarding perioperative risk of resection with primary
      anastomosis (n = 94). 53 of them had peridiverticulitis with stenosis (mortality
      0), 41 had emergency operations (mortality 14.6%). Hartmann procedure (n = 13,
      mortality 7.6%) has been accepted only for the following situations: 1. ileus
      with secondary damage of the bowel, 2. extended diffuse peritonitis with
      secondary organ failure, 3. poor blood supply of the bowel, 4. the patient under
      immunosuppression after transplantation. Regarding these recommendations
      mortality rate in emergency operations (12.9%) has been lower as compared to 15
      to 20% in literature. So regarding the recommendations named above resection with
      primary anastomosis seems to be a safe procedure in complicated diverticulitis.

PMID- 8149801
TI  - [Lichtenstein herniotomy].
AB  - All standard methods of hernia repair involve suturing together tissues which are
      not normally in apposition. This violates the basic surgical principle that
      tissue must never be approximated under tension and accounts for an unacceptable
      number of failures. Total reinforcement of the inguinal floor with a sheet of
      suitable biomaterial and employment of a "tension-free" technique is a more
      effective approach. Since June 1984, 3250 primary inguinal hernias have been
      repaired at the Lichtenstein Hernia Institute by the open tension-free technique
      using Marlex mesh. All operations were performed under local anesthesia. Patients
      were discharged from the hospital within two or four hours after the operation.
      The patients were followed from one to 8 years by physician examination. The
      follow-up rate was 87%. There were four recurrences. The causes of recurrence and
      how to avoid them are discussed.

PMID- 8149802
TI  - [Lichtenstein patch versus Shouldice technique in primary inguinal hernia with a
      high risk of recurrence].
AB  - 209 primary inguinal hernias in patients older than 60 years with high risk for
      recurrence and for surgery were randomly allocated to Shouldice repair (107
      hernias) or Lichtenstein patch (102 hernias). Over a 30 months period there was
      one recurrence in the Lichtenstein group. The amount of local anesthetic and
      postoperative pain medication was significantly reduced in the Lichtenstein
      group, 9.8% of repairs requiring no pain medication at all, and 29.4% none on the
      first postoperative day. No other hernia repair is as painless, innocuous, and
      easily performed under local anesthesia as the Lichtenstein patch. Both,
      Lichtenstein and Shouldice, serve their purpose almost ideally when done
      correctly.

PMID- 8149803
TI  - [Laparoscopic surgery of inguinal hernia by transperitoneal implantation of an
      artificial mesh. Technique and early results].
AB  - We report on 250 patients with 342 inguinal hernias operated laparoscopically by
      pre-peritoneal implantation of a prosthetic mesh. 167 hernias were indirect, 175
      direct, including 92 bilateral, 71 recurrent and 4 femoral hernias. There were
      four major complications: two lesions of the urinary bladder, treated in one case
      by laparotomy and two foreign body reactions against the mesh, which had to be
      removed. Two recurrences (0.6%) occurred during a 2-12 months follow-up. The mean
      hospital stay was 4 (3-10) days. Return to full activity was possible after one
      week.

PMID- 8149804
TI  - [Ruptured cystadenoma of the pancreas].
AB  - There are many potential reasons for an acute abdomen. Very rare is a rupture of
      a cystadenoma of the pancreas. We describe such a case of an 85-year old woman,
      who was treated with an internal drainage of the cyst with a Roux-Y-loop, as at
      the time of the emergency operation the histological diagnosis was not known. As
      for the age of the patient and her general condition a secondary procedure with
      total resection of the mucinous cyst was not carried out. The post-operative
      course was uneventful up to three months, when the patient died in a geriatric
      home due to a antibiotic-resistant urosepsis. Literature is reviewed and our case
      is discussed in respect to recent publications.

PMID- 8149805
TI  - [Intestinal obstruction with invagination caused by an inflammatory fibroid polyp
      of the small intestine].
AB  - We observed the rare case of a 50-year-old man with intestinal obstruction due to
      an inflammatory fibroid polyp (IFP) of the jejunum. Here, we report its clinical
      and pathological characteristics, and its histologic appearance. Limited small
      bowel resection led to complete recovery of the patient. In a short review of the
      literature, possible pathogenetic mechanisms as well as diagnostic and
      therapeutic means are discussed. Although rare, IFP should be considered in the
      differential diagnosis of small bowel obstruction.

PMID- 8149806
TI  - [Intraosseous lipoma of the calcaneus].
AB  - This report presents one case of rare benign intraosseus lipoma of the os calcis,
      which is analysed under the clinical, histopathologic and radiologic view. Not
      only the radiographic but also the computed tomographic findings has shown a
      typical picture of an intraosseous lipoma including a central calcification. In
      order to exclude a malignant transformation and as a prophylaxis of a
      pathological fracture the operative removal and bone graft transplantation is
      considered as therapy of choice.

PMID- 8149807
TI  - [What is a septic patient?].

PMID- 8149808
TI  - The central region of the synaptonemal complex in Blaps cribrosa studied by
      electron microscope tomography.
AB  - The synaptonemal complex (SC) in the beetle Blaps cribrosa contains a highly
      organized central element (CE), two flanking lateral elements (LEs), and a number
      of regularly spaced transverse filaments (TFs) crossing the central region. The
      CE is built like a ladder with two longitudinal components running in parallel
      and a number of regularly spaced transverse CE components, bridging the two
      longitudinal components. The CE is multi-layered with the ladders of the
      individual layers more or less in register. Essentially every TF originates in
      one of the LEs, crosses the CE through a transverse CE component and reaches the
      opposite LE; every transverse CE component in a given layer corresponds to one,
      and only one, TF. In a CE layer, short irregular pillars form the junctions
      between the transverse and longitudinal CE components. Adjacent pillars are
      connected to each other by fine fibrous bridges: the two pillars in the same
      transverse CE component are linked, and so are the pillars along each
      longitudinal component, and also more occasionally adjacent pillars in separate
      CE layers. It is proposed that a TF with the two associated short pillars
      represents the structural unit in the central region. The ordered structure of
      the CE is accomplished by linking adjacent pillars to each other into the well
      defined three-dimensional organization of the CE.

PMID- 8149809
TI  - The three-dimensional structure of the central region in a synaptonemal complex:
      a comparison between rat and two insect species, Drosophila melanogaster and
      Blaps cribrosa.
AB  - The highly ordered central region of the synaptonemal complex (SC) in Blaps
      cribrosa has recently been studied by electron microscope tomography (EMT), and a
      simple three-dimensional model presented. Using the same experimental approach we
      have now compared the central region in Blaps with the central regions in
      Drosophila melanogaster and rat. In all three species, the SCs exhibit a central
      element (CE) flanked by two lateral elements (LEs). The central region between
      the two LEs is crossed by transverse filaments (TFs). The Blaps CE element is the
      most ordered one with a well-defined ladder-like structure with two longitudinal
      components bridged by a number of regularly spaced transverse components, the
      rungs of the ladder. At the junctions between the longitudinal and transverse
      components there are prominent dense structures. The CE is multi-layered with the
      ladders of the separate layers in approximate register. In Drosophila the
      transverse CE components are as distinct and well organized as in Blaps, while in
      rat they are present but are less frequent and less well ordered. The
      longitudinal CE components in Drosophila are often fragmented and even more so in
      rat. The tomographic analysis revealed that in all three species the central
      region contains the same structural units: a single TF associated with two short
      pillars (or globules), which correspond to the junction structures. A fibrous
      lattice connects the two pillars/globules on the same TF forming the transverse
      CE component and those on adjacent TFs forming the longitudinal CE component;
      fibers between pillars/globules also link consecutive CE layers together. In the
      longitudinal component the number of fibrous bridges between the pillars/globules
      is related to the conspicuousness of the longitudinal component, i.e. Blaps has
      most, Drosophila almost as many, and rat considerably fewer bridges. We conclude
      that the central region in rat, Drosophila and Blaps contains the same basic
      structural unit but the degree of order and concentration of the units differ: a
      higher density seems to be accompanied by a higher order within the CE.

PMID- 8149810
TI  - A new type of ribonucleoprotein constituent of the polytene nucleus of the
      salivary glands of Chironomus thummi and Ch. tentans.
AB  - Using electron spectroscopic imaging, a new type of small granular structural
      constituent has been observed in the extrachromosomal zone of the polytene
      nucleus of the salivary gland cells of Chironomus thummi and Chironomus tentans.
      These granules appear isolated or in small clumps and are often seen to be
      connected with surrounding thin fibrils. They are stained by the EDTA procedure,
      which is preferential for nuclear ribonucleoprotein (RNP) constituents, and by
      the bismuth oxynitrate method for visualizing phosphorylated compounds. The
      granules are 15-23 nm in diameter and are digested by prolonged post-embedding
      RNAse hydrolysis. These structural elements contain the highest concentration of
      phosphorus in the interchromosomal space as revealed by electron energy loss
      spectroscopy. The small granules exhibit several morphological and cytochemical
      features in common with interchromatin granules, but they are not labeled with
      antibodies directed against extranucleolar small nuclear RNPs (snRNPs), as are
      interchromatin granules.

PMID- 8149811
TI  - In human chromosomes telomeric regions are enriched in CpGs relative to R-bands.
AB  - Human chromosomes were in situ nick-translated using as nicking agents the
      endonucleases MspI (CCGG), its methyl-sensitive isoschizomer HpaII, HaeIII
      (GGCC), SacII (CCGCGG), EcoRI (GAATTC) and DNaseI. We show that in metaphase
      chromosomes R-bands are enriched, as compared with G-bands, in the dinucleotide
      CpG but no more than what is expected on the basis of their relative G+C content.
      The telomeric regions, on the contrary, besides having a chromatin conformation
      that is particularly relaxed and accessible to endonucleases, also show an
      enrichment in CpGs.

PMID- 8149812
TI  - Analysis of Drosophila chromosome 4 using pulsed field gel electrophoresis.
AB  - Previous estimates of the size of Drosophila melanogaster chromosome 4 have
      indicated that it is 1% to 4% of the genome or approximately 6 Mb. We have used
      pulsed field gel electrophoresis (PFGE) to separate megabase-sized molecules of
      D. melanogaster chromosomal DNA. Southern blots of these gels were probed with
      DNA fragments from the cubitus interruptus and zfh-2 genes, which are located on
      chromosome 4. They each identify the same-sized distinct band that migrates at
      approximately 5.2 Mb in DNA preparations from the Kc cell line. We interpret this
      band to be intact chromosome 4. In DNA obtained from embryos of various D.
      melanogaster wild-type strains, this chromosome band showed strain-specific size
      variation that ranged from 4.5 to 5.2 Mb. The D. melanogaster chromosome 4 probes
      also identified a single, 2.4 Mb band in embryonic DNA from Drosophila simulans.
      We conclude that D. simulans chromosome 4 is substantially smaller than that of
      D. melanogaster, presumably owing to differences in the amount of heterochromatic
      DNA sequences. Our simple DNA preparation from embryos and PFGE conditions should
      permit preparative isolation of chromosome 4 DNA and will facilitate the
      molecular mapping of this chromosome.

PMID- 8149813
TI  - Preparation and karyotype analysis of mitotic chromosomes of the freshwater
      sponge Spongilla lacustris.
AB  - The present study documents for the first time the karyotype and mitotic
      chromosomes of a sponge. For the studies the freshwater sponge Spongilla
      lacustris (Lin. 1758) was used. Its karyotype comprises nine different chromosome
      pairs ranging in size from 2.1 to < or = 0.7 microns. Changes in size and shape
      of the chromosomes during the progression of mitosis are documented both light
      and electron microscopically. The data reveal that the lowest multicellular
      eukaryotes, the sponges, have already reached a high level of evolution of the
      mitotic mechanism.

PMID- 8149814
TI  - The spatial arrangement of Allium triquetrum chain quadrivalents at metaphase I
      as reviewed by confocal microscopy.
AB  - We examined the three-dimensional arrangement of bivalents and, in particular, a
      chain of four chromosomes (chain quadrivalent) in the metaphase I spindle of
      pollen mother cells of Allium triquetrum by confocal microscopy. Firstly, we show
      by optical sectioning and three-dimensional image reconstruction that the
      cooriented pairs of centromeres of all seven bivalents lie virtually parallel to
      each other in the metaphase I spindle, parallel to the long axis of the spindle.
      Secondly, we likewise show that the four centromeres of the chain quadrivalent
      are aligned in the metaphase I spindle in, essentially, a two-dimensional array,
      not in a three-dimensional array, as proposed by some other authors. This two
      dimensionality has its basis, we argue, in the principle that poleward directed
      spindle forces minimise centromere-to-pole distances and therefore align pairs of
      centromeres connected to opposite poles most axially (vertically) in the spindle.
      These distances are minimised for the quadrivalent as a whole only when it lies
      in two dimensions, i.e. in a plane parallel to the spindle axis.

PMID- 8149815
TI  - The salivary gland chromosomes of Drosophila virilis: a cytological map, pattern
      of transcription and aspects of chromosome evolution.
AB  - By combining information from microscopical observation and photography a
      graphical map of Drosophila virilis salivary gland chromosomes was constructed.
      About 1,560 individual bands are shown and patterns of transcription at about 360
      sites are indicated. The application of the map is demonstrated by using genetic,
      morphological and in situ hybridization data to identify the white-Notch regions
      of D. virilis and Drosophila melanogaster as homologous chromosome segments with
      constant and variable features.

PMID- 8149816
TI  - Agricultural development paths and pest management: a pragmatic view of
      sustainability.
AB  - Historical profiles can be used to portray past pathways of agricultural
      development, the factors that affected pest status and the responses made by
      farmers in the form of pest management. Understanding the key factors affecting
      these historical developments is thought to be crucial for identifying likely
      future scenarios and associated opportunities and constraints for improving pest
      management. Evidence for this view is provided by four case studies: brassica
      pests in the United Kingdom; tsetse fly and trypanosomiasis management in The
      Gambia; rice pest management in the Lop-Buri area of Thailand; and pest
      management in dryland cotton in north-east Australia.

PMID- 8149817
TI  - Systems of plant protection.
AB  - A framework for associating pest management with farming systems may be
      characterized by a cropping index (number of crop cycles per year); a plant
      species homogeneity rank, described as the degree of monoculture or polyculture
      and intensity of use of modern, high-yielding varieties versus land races or
      traditional varieties; intensity of use of synthetic agrochemicals; the
      availability of societal infrastructure to support agriculture, such as
      irrigation and roads; and availability of support services such as credit,
      public/private sector research and extension services. Traditional methods of
      plant protection in the tribal areas of the Philippines rely heavily on ritual
      based cultural practices that recognize the crop calendar and its activities as
      part of a larger social agenda. Most groundnut growers in West Africa utilize
      minimal inputs with little infrastructural support but they have often adopted
      improved varieties. Extensive farming systems with modern inputs are exemplified
      by wheat in the mid-western USA, where pests are managed mainly through host
      plant resistance. In intensive farming systems--vegetables in South-East Asia,
      wheat in The Netherlands and orchards in the USA--crop intensification is
      greatest and pest problems arising from overuse of pesticides are most
      noticeable. Unsustainable farming systems evolve if realistic plant protection is
      not taken into consideration.

PMID- 8149818
TI  - Integrated management of plant viral diseases.
AB  - Viral diseases of plants cause enormous economic losses particularly in the
      tropics and semitropics which provide ideal conditions for the perpetuation of
      viruses and their vectors. Intensive agricultural practices necessitated by the
      ever-increasing demands of the rapidly growing population and the introduction of
      new genotypes, cropping patterns and crops have further aggravated the problem of
      viral diseases. Many diverse approaches have been tried to minimize the losses
      caused by these diseases. The approaches are mainly based on avoidance of sources
      of infection; avoidance or control of vectors; modification of cultural
      practices; use of resistant varieties obtained though conventional breeding
      procedures; cross protection; systemic acquired resistance; and use of transgenic
      plants containing alien genes that impart resistance to viruses. Although the use
      of resistant varieties has been found to be the most economical and practical,
      for effective management of viral diseases an integrated approach is essential in
      sustainable agriculture. Development of integrated management practices also
      requires correct identification of the causative viruses, because symptoms can be
      misleading, and adequate understanding of the ecology of viruses and their
      vectors.

PMID- 8149819
TI  - Agriculture in Gloria Land.
AB  - A farming system has been developed on the Gloria Land farm at the Sri Aurobindo
      Ashram that uses purely organic materials and achieves yields comparable with or
      better than those on conventional farms under similar agroclimatic conditions.
      The stimulus for the conversion to organic farming came from observations of the
      toxicity of chemical pesticides and their apparent ineffectiveness in reducing
      the impact of pests and diseases. On the Gloria Land farm, a carefully integrated
      mixture of activities includes crop growing, animal husbandry, fish rearing and
      sericulture. Sufficient organic waste is produced to fulfill at the needs of the
      farm's crops. Energy is partially supplied by biogas produced on the farm. This
      system is economically viable and ecologically sustainable.

PMID- 8149820
TI  - The local view on the role of plant protection in sustainable agriculture in
      India.
AB  - Indiscriminate use of chemical insecticides has affected humans and their
      environment and contributed significantly to reduced productivity of crops. With
      the increasing realization of the importance of sustainable agriculture, the
      concept of integrated pest management (IPM) for sustainable agriculture has
      emerged. In the recent past entomologists and the farmers have identified methods
      of pest management that are ecologically non-disruptive and stable. Concurrently
      indigenous crop varieties with resistance to pests and diseases have been
      developed and cultivated. According to the principle of 'organic farming',
      several non-chemical methods have become popular among the local farmers. Simple
      cultural practices like increasing the seed rate to compensate for pest damage,
      adjusting the time of sowing to avoid pest damage, mulching, intercropping, trap
      cropping and crop rotation have been found to provide adequate protection from
      pest damage with no additional cost and without harmful effects on the
      environment. The age-old method of catch and kill is still being practised by
      farmers, particularly for cotton. Mechanical methods like the bow trap for
      control of rats and provision of tin sheets around coconut tree trunks to prevent
      rats damaging the nuts are still being adopted. The use of botanical materials
      such as the neem products for pest management has been well received almost all
      over the world. Biological control using the natural enemies of insect pests has
      become very popular among the farmers in the 1980s. The farmers who clamoured for
      chemical pesticides in the 1960s and 1970s are now disillusioned with these
      poisonous eco-destabilizing substances; they want sensible, biologically rational
      methods of IPM. Pest surveillance and monitoring play an important role in IPM
      for sustainable agriculture.

PMID- 8149821
TI  - Communication and implementation of change in crop protection.
AB  - The slow adoption of integrated pest management (IPM) has been attributed to the
      widespread gaps in farmers' knowledge of rational pest management. Other factors
      such as farmers' perception of high input use and promotion of pesticides also
      influence decisions to practise rational pest management. To bridge these gaps
      and improve farmers' pest management practices, most IPM implementation
      programmes rely on communication strategies. These communication approaches
      utilize either mass media or interpersonal channels or a combination. The choice
      of which communication approach to employ depends on project objectives and
      resources. Among extension and communication approaches used in crop protection,
      strategic extension campaigns, farmer field schools and farmer participatory
      research stand out in their ability to bring about significant changes in
      farmers' pest management practices. While extension campaigns have greater reach,
      farmer participation and experiential learning achieve more impact because
      learning effects are sustained. Communication media are important in raising
      awareness and creating a demand for IPM information but interpersonal channels
      and group methods such as the farmer field school and farmer participatory
      research are essential to accomplish the tasks of discovery and experiential
      learning of IPM skills.

PMID- 8149822
TI  - The ecological background of food production.
AB  - In the industrialized countries dramatic decreases in the number of people
      employed in agriculture have been made possible by a rise in soil and labour
      productivity. There is scope for these to improve further, particularly in
      developing countries. Potential yields are determined by the characteristics of
      the crop, local temperature and sunlight. Because the availability of nutrients
      and that of water are limiting for at least part of the growing season in most
      agricultural lands, attainable yields are lower than potential yields. Proper
      management of nutrient inputs, such that optimum use is made of each, can reduce
      this gap without causing negative environmental side-effects. Actual yields are
      lower than attainable yields because of growth-reducing factors, such as pests,
      diseases and weeds. For sustainable agriculture these should be controlled mainly
      by biological measures. There are many possibilities for this, thus biocides may
      be used as a last resort not as preventive insurance. Potential yields of rice
      and sugarcane can reach 30,000 kg ha-1 per year of consumable organic matter,
      sufficient to feed 120 people. Such yields cannot be achieved on all agricultural
      land, but it is estimated that world food production could support a population
      of 80 thousand million, if they were all vegetarian and required only 1500 m2 for
      non-food-related purposes. The green revolutions that occurred in the Western
      industrialized countries in the late 1940s and early 1950s and in Asia in the
      late 1960s and early 1970s need to be followed by a similar increase in
      agricultural productivity in Africa and West Asia to feed their rapidly growing
      populations. Better use of fertilizers and good water management require well
      educated farmers with the financial means to implement long-term strategies. If
      these developments are managed properly, food production for the ever-increasing
      human population can be guaranteed and the burden on the environment and natural
      habitats reduced, enabling the development of sustainable agricultural systems.

PMID- 8149823
TI  - Plant diseases in India and their control.
AB  - The concept of development is reviewed in terms of sustainability. Food
      production in India driven by pressure from an increasing human population uses
      90,000 t per year of technical-grade pesticide: 12% of this is fungicide and a
      good part is insecticide for the control of vectors of plant viruses. A change in
      the cropping pattern and irrigation have provided a summer 'green bridge' along
      Tamil Nadu/Andhra Pradesh border areas for the tungro virus that affects rice and
      its vector. Epidemics occur along the coramandal coast, if the weather is
      suitable. Red rot disease of sugarcane is promoted by poor drainage, river
      widening, ratooning, contaminated planting material and variation in the pathogen
      throughout the Indo-Gangetic plain. Apple production uses large amounts of
      fungicide. For every 1000 t of apples produced 1t of fungicide is sprayed 8-10
      times sequentially. Systemic application of fungicides has led to pesticide
      resistance and resurgence of other diseases. 70-80% of the Nagpur Mandrin produce
      reaches the market by trucks that have to traverse 1000 km. 10.6% of fruits are
      lost to post-harvest diseases; culling, sunburn and injuries account for another
      11.6%. In the control of leaf rust of wheat in North India, the use of varietal
      mosaics, resistance genes and extra-late wheat sowings that do not coincide with
      favourable weather have all collectively contributed to loss reduction. The drop
      in the production of exportable crops such as peppers and coconuts because of
      diseases needs attention. The traditional wisdom on crop mixtures, organic
      manuring, shifting sowings, etc, needs scientific re-evaluation.

PMID- 8149824
TI  - Sustainable agriculture and integrated pest management in China.
AB  - In developed countries, emphasis is being switched from high productivity through
      the use of high inputs to ecologically sustainable agriculture. In developing
      countries such as China priority must be given to increasing food production
      while simultaneously trying to optimize sustainability. Achievements in plant
      protection are being countered by continued evolution of the pest ecosystem, in
      part driven by application of pesticides or the introduction of new crop
      varieties. Future management of the agricultural ecosystem requires the
      development of a method of 'super-long-term' prediction to evaluate possible
      consequences of different strategies of plant protection. Crop plants with
      durable resistance to pests must be derived by conventional breeding or by using
      biotechnology and genetic engineering. Genetic vulnerability can also be reduced
      by techniques such as gene rotation and mixed cropping. Biological control of
      plant pests shows promise but requires ecological study of the relationships
      among crop, pest and natural enemy. Implementation of sustainable pest management
      will need training and education of farmers, extension workers and policy makers
      to deliver new information in the developing countries.

PMID- 8149825
TI  - Towards the rational management of the insect pests of tropical legume crops in
      Asia: review and remedy.
AB  - The productivity of legume crops, especially the pulses, has not increased
      markedly in 30 years. This is a serious matter in this time of exponential human
      population growth because legume crops provide essential diet components that are
      not present in cereals at a price that is affordable to the majority. The
      preferential allocation of research resources to cereal crops is one reason for
      this stagnation. I suggest that an international effort should be mounted to
      redress this situation. Most Asian legumes have in common a cadre of insect pests
      that are reducing yields to levels at which harvesting is not economic. The
      position is worsening because insecticide resistance in key production areas has
      rendered many species uncontrollable. The short-term remedy is to persuade
      farmers to reduce their dependence on insecticides. Long-term solutions should be
      aimed at a common policy centred on the principal components of integrated pest
      management (IPM) schemes. Governments should be supplied with information that
      will permit them to set priorities according to absolute crop loss indicators.
      These will in turn provide a rational basis for the subsequent development of
      regional strategies. The establishment of an IPM centre in Asia would support the
      facilitation of this ideal. Such an organization would become the focal point for
      collecting, developing and disseminating the information and technology needed to
      make a quantum leap in legume production.

PMID- 8149826
TI  - Perspectives for crop protection in sustainable agriculture.
AB  - The challenge facing agriculture, particularly in developing countries, is to
      increase productivity without causing ecological damage. An important aspect of
      sustainable agriculture is the substitution of chemicals and capital with locally
      grown biological inputs and knowledge. Production of food grains in India has
      risen steadily since the 1960s, partly through the introduction of high-yielding
      varieties of rice and wheat together with appropriate agronomic and plant
      protection practices. Plant breeding programmes have improved cultivated rice by
      the transfer, from wild species, of genes conferring resistance to viral
      diseases. Diversification of resistance is sought, to render the hybrids less
      vulnerable to sudden outbreaks of diseases and insect pests. For wheat,
      resistance to rusts involves the additive interaction of several gene-encoded
      traits. Linkage of resistance genes with morphological markers enables the
      inheritance of the former to be followed easily. It is important that recent
      advances in molecular genetics are incorporated into integrated pest management
      programmes. This will require appropriate social organization. Research centres
      that develop and exploit genetic sources of resistance and varietal
      diversification should be established.

PMID- 8149827
TI  - Sustainable agriculture: an explanation of a concept.
AB  - Close relationships between agriculture and many areas of human activity
      determine countless interlinkages with global issues of natural environment
      protection, human population increase, food supply, industry and world trade.
      This broad context promotes different perceptions of sustainable agriculture by
      different interest groups. Profitable diversification away from overproduction of
      basic commodities and satisfaction of environmental pressure groups are major
      preoccupations in developed countries. Elsewhere the main concerns is to maintain
      a trend of increasing production: food security with a future dimension.
      Achieving this depends essentially on protecting the agricultural resource base.
      Inputs and input substitution are important co-related issues but the core of
      sustainability is the avoidance of any attrition of the potential for future
      production; this demands that we guard soil, water sources, grazing lands and
      gene pools against loss and degradation. Though superficially biophysical or
      technical in nature, most problems of resource degradation and eroding potential
      are rooted in economic, social and political issues; few such problems will be
      solved unless the primacy of these issues is recognized and addressed.
      Sustainable agriculture will likely remain elusive until governments and other
      agencies accept it as arising only as the outcome of a synthesis of strategies on
      population, employment, economic planning, technical research and national
      investment.

PMID- 8149828
TI  - Crop protection: why and how.
AB  - The answer to the question 'why' has proximate and ultimate roots. The proximate
      answer, 'pests take our harvest', compels one to act. Crops and their pests are
      products of domestication, the ancestors of the pests still exist in nature.
      Eradication is impossible and undesirable. What action should be taken? The
      ultimate answer, how organisms became pests, may tell us how to act. Old cropping
      systems had man-made ecological sustainability but do not have economic
      sustainability in modern times. To achieve both we must prevent rather than
      control pest outbreaks, using old and new ecological tricks, with application of
      pesticides in emergency cases only. The action will require a move from chemistry
      to ecology. Optimism on regaining some ecological sustainability is mixed with
      doubts on economic sustainability. Can farmers be asked to invest in the future
      at the expense of today's family income? Crop protection faces new technical and
      moral problems.

PMID- 8149829
TI  - The economics of food production.
AB  - Although world average food production per person is increasing there are many
      countries, particularly in sub-Saharan Africa, where production has fallen in
      recent decades. The economic analysis of the world food problem concerns the
      dynamics of production, income, growth, demand and trade. The 'law of diminishing
      returns' suggests that labour incomes fall as population density increases.
      Capital investment and technological change, particularly with a land-saving
      bias, can overcome this effect. Such land-saving innovations are less appropriate
      where population densities are lower, as in much of sub-Saharan Africa.
      Innovations which reduce risk, such as stress- and disease-resistant crop
      varieties, may be more attractive to farmers. Communal or government action is
      required to ensure sustainability of food production; to reduce risk, through
      price stabilization, possibly crop insurance and contingency plans for famine
      relief; to promote equity and to ensure competitive market conditions. Public
      funding of agricultural research is necessary to promote growth in food supplies.
      If increases in supply do not keep pace with growth in demand, food prices rise,
      attracting resources into food production. If supply grows faster, food prices
      and farm incomes fall, driving resources out of agriculture. Resources may not
      move fast enough to correct imbalances. Primary producers are likely to face
      deteriorating terms of trade. Linkages between food production and other sectors
      are weak, so primary exports are not a good basis for economic development.
      Import substitution strategies may damage agriculture. Structural adjustment
      regimes have been adopted in some countries to correct imbalances and provide an
      incentive for farmers to increase production. Associated reductions in public
      expenditure may have a contrary impact.

PMID- 8149830
TI  - Government intervention in crop protection in developing countries.
AB  - Government interventions in the pesticide market are necessary, particularly in
      developing countries because of a high likelihood of market failure. The green
      revolution in Asia made governments introduce programmes which relied heavily on
      pesticide-based solutions to pest problems. With growing environmental concerns
      in donor and developing countries, a higher priority is given to natural factors
      of control. From a review of various types of government interventions it is
      concluded that government investments related to pest management should focus on
      reducing the dependence on pesticides rather than concentrating on the
      minimization of their side-effects.

PMID- 8149831
TI  - Why do functional gastrointestinal disorders come and go?

PMID- 8149832
TI  - Effect of constant light on rhythmic gastric functions in fasting rats.
AB  - The effects of four weeks of continuous illumination (LL), a subacute stress, on
      gastric mucosal endogenous aggressive and defensive factors were studied. Young
      male Sprague-Dawley rats were used with two different illumination regimens: LL
      and 12 hr light/12 hr dark (LD). At the end of three to four weeks of either
      regimen of illumination, gastric acid secretion, pepsin secretion, mucus
      secretion, and potential difference (PD) were studied. All gastric parameters,
      except mucus secretion, were significantly reduced by LL. The reduction in acid
      secretion (13.3%) was not significant after Bonferroni correction for the four t
      tests Pepsin secretion and PD were 27.9% and 24.6% less, respectively. These
      differences were significant after Bonferroni correction. The LD rats showed
      significant circadian rhythms for acid, mucus, and pepsin secretion. The LL rats
      showed significant rhythmicity for these same parameters with period lengths
      different from 24 hr. Gross inspection of the gastric mucosa indicated that 69.8%
      of the LL rats had lesion scores of 1.0 or higher, while none of the LD rats had
      scores above 0.5.

PMID- 8149833
TI  - Effect of intraduodenally administered histamine on gastric acid secretion in
      rats and guinea pigs.
AB  - We examined the effect of histamine administered intraduodenally as well as
      subcutaneously or intravenously on the gastric acid secretion in rats and guinea
      pigs, using a newly devised cannula. Intraduodenally administered histamine
      dihydrochloride caused a significant dose-dependent increase in the gastric acid
      secretion in rats. The maximal acid secretion, which corresponded to that after
      subcutaneous (20 mg/kg) or intravenous (10 mg/kg/hr) administration of histamine,
      was observed within 30 min after intraduodenal administration (40 mg/kg). The
      plasma concentrations of histamine determined 30 min after intraduodenal,
      subcutaneous, and intravenous administration of histamine were nearly the same.
      Pretreatment with aminoguanidine sulfate (diamine oxidase inhibitor) at 30 mg/kg
      significantly increased the gastric acid secretion caused by intraduodenal
      histamine. The gastric acid secretion stimulated by intraduodenal histamine was
      significantly inhibited by cimetidine, pirenzepine, and omeprazole, but remained
      unchanged with tripelennamine. Intraduodenal histamine (20 mg/kg) also maximally
      stimulated the gastric acid secretion in guinea pigs. The response was comparable
      to that with subcutaneous histamine (1 mg/kg). We conclude that intraduodenal
      histamine has the ability to stimulate gastric acid secretion in both rats and
      guinea pigs.

PMID- 8149834
TI  - Bleeding peptic ulcer occurring in hospitalized patients: analysis of predictive
      and risk factors and comparison with out-of-hospital onset of hemorrhage.
AB  - We reviewed 84 consecutive cases of peptic ulcer hemorrhage, which occurred, in
      an area of 270,000 people, from 1986 to 1988, in patients already hospitalized
      for other diseases (in-bleeders). These subjects were compared with a prospective
      series of 386 patients who initially bled as out-patients and were then admitted
      (out-bleeders). Of 84 hemorrhages in hospitalized patients, 41 followed major
      surgery, while 43 were associated with other severe conditions. Bleeding site was
      duodenal in two thirds. Mean age was 67 +/- 15 years versus 59 +/- 15 among out
      bleeders. Fifty percent of in-bleeders had recently received nonsteroidal
      antiinflammatory drugs (NSAIDs), and one third were on anticoagulants and 10% on
      corticosteroids; in 39 (46%) bleeding was shown to be persistent or recurrent, 5
      (5.9%) underwent endoscopic and 18 (21%) surgical therapy; 29 died (34%). The
      corresponding figures among out-bleeders were: further bleeding 80 (20.7%),
      endoscopic therapy 12 (3.1%), surgery 25 (6.5%), deaths 17 (4.4%). As regards in
      bleeders, only active bleeding and endoscopic stigmata emerged as statistically
      significant risk factors for further bleeding. The latter was shown to be
      significantly related to mortality. The most relevant finding was, however, that
      NSAIDs and anticoagulants, in association with stress and aging, are very
      frequently involved in peptic ulcer bleeding of hospitalized patients. The fatal
      outcome of one third, despite all available treatments, highlights the importance
      of prevention against drug- and stress-related mucosal damage in in-patients
      suffering from severe diseases.

PMID- 8149835
TI  - Adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, and
      catalase activities in gastric juices from patients with gastric cancer, ulcer,
      and atrophic gastritis.
AB  - Adenosine deaminase (ADA), 5'-Nucleotidase (5NT), Xanthine oxidase (XO), Cu-Zn
      Superoxide dismutase (SOD) and Catalase (CAT) activities were determined in
      gastric juices from patients with gastric cancer, ulcer, gastritis and from
      healthy subjects. Enzyme activities were given as units per ml gastric juice and
      units per mg protein in gastric juice. ADA, 5NT and XO activities were found
      lower and protein concentrations were found higher in the cancer group than
      controls. There was however no significant difference between Cu-Zn SOD
      activities of the cancer and control groups. In all groups including control one,
      we could not find catalase activities in most of the samples. On the other hand,
      ADA, 5NT activities and protein concentrations in the gastric juice were lower in
      the gastritis group than control group. In the ulcer group, we found higher Cu-Zn
      SOD and XO activities and lower 5NT activity and protein concentrations compared
      with control values. In an attempt to establish statistical correlations between
      mean enzyme activities, pH and protein concentrations in the gastric juices of
      the groups, we found noticeable intra and inter-correlations, which indicated
      possible relations between DNA and free radical metabolizing enzymes.

PMID- 8149836
TI  - Ornithine decarboxylase (ODC) levels in children with reflux esophagitis.
AB  - Reflux esophagitis is a common disease in infants and can be diagnosed largely by
      esophageal biopsy. In adults, chronic esophagitis may lead to Barrett's
      esophagus, a premalignant condition for esophageal cancer development. Ornithine
      decarboxylase (ODC) is used as an early marker for colon cancer development. No
      data are available on the role of ODC in reflux esophagitis in the pediatric
      population. In this study we retrospectively analyzed ODC activity in esophageal
      biopsies of children who underwent upper endoscopy. According to the esophageal
      histology, patients were divided into three groups: normal mucosa, mild, and
      moderate/severe esophagitis. None of our patients had esophageal metaplasia or
      cancer. ODC level was significantly higher in the moderate/severe esophagitis
      group compared to mild and normal mucosa group. We conclude that ODC activity is
      directly proportional to the severity of the esophageal inflammation/regenerative
      process in children with reflux esophagitis.

PMID- 8149837
TI  - Gastric emptying of solid meals in achalasic patients after successful pneumatic
      dilatation of the cardia.
AB  - Gastric emptying of a solid meal was measured by ultrasound scanning in 16
      achalasic patients following successful pneumatic dilatation of the lower
      esophageal sphincter. The data were compared with those of a control group of 15
      healthy subjects. Fasting and maximal postcibal antral sections were very similar
      in the two groups. On the contrary, the time interval before maximal antral
      dilatation, and the time necessary for the emptying of half or of the whole meal
      were significantly longer in the achalasic patients than in the controls. Half of
      the achalasic patients had longer emptying times than the upper normal limit. The
      percentage of the meal retained in the antrum at each hourly interval was
      significantly higher in the achalasic group. The finding of a high prevalence of
      gastric emptying disturbances suggests that the functional derangement in
      achalasia is not limited to the esophagus.

PMID- 8149838
TI  - Long-term follow-up of consequences of percutaneous endoscopic gastrostomy (PEG)
      tubes in nursing home patients.
AB  - PEG (percutaneous endoscopic gastrostomy) tubes are frequently placed in nursing
      home patients. The aim of this study was to assess retrospectively the long-term
      changes in functional and nutritional statuses, tube-related complications, and
      factors influencing survival in 46 nursing home residents, mean age 73.6 years
      (range 19-96). Functional status was evaluated by a standard rehabilitation
      medicine scale. Nutritional status was evaluated by serum albumin and cholesterol
      concentrations and by weight. PEG-related complications requiring hospitalization
      or emergency room or clinic evaluations were noted. Additionally, changes in
      resuscitation status were noted. The predominant indication for PEG placement was
      dementia (52%). At PEG placement, 48% of patients had total functional
      impairment. Regardless of the severity of impairment, no patient's functional
      status improved after PEG. Nutritional status did not improve significantly.
      Mortality approached 50% and 60% at 12 and 18 months, respectively, and was
      significantly related to age, resuscitation status, and serum albumin
      concentration. All patients under 40 years of age at PEG survived, in contrast to
      41.3% of patients over 40 years of age (P < 0.001). Sixty-three percent of
      patients who were "full code" at PEG placement survived, in contrast to 10% of
      "no code" patients (P < 0.001). Albumin > or = 3.5 g/dl at PEG or thereafter was
      associated with improved survival (P < 0.001) as compared to albumin < 3.5 g/dl.
      PEG-related complications occurred in 34.7% of patients, and the first occurred
      four months after PEG. We conclude that realistic expectations of what PEG can
      accomplish be a factor in the decision to place a PEG tube in nursing home
      patients.

PMID- 8149839
TI  - Acute gastritis associated with spiral organisms from cats.
AB  - Numerous studies implicated Helicobacter pylori as one causative agent producing
      gastritis and dyspepsia. Recent reports focus on another bacterium,
      Gastrospirillum hominis, as a possible pathogen producing gastritis. We report a
      30-year-old researcher who became acutely ill with epigastric pain indicative of
      esophagitis or peptic ulcer disease. Gastritis and a gastric ulcer were observed
      endoscopically. Histological examination of the gastric mucosa revealed an acute
      gastritis and large spiral-shaped organisms. The spiral forms were present in
      large quantities in the gastric mucosa of experimental animals (cats) handled by
      the patient in his research. Electron microscopy confirmed that the organisms
      from the cat and patient were morphologically identical. The patient was
      successfully treated with bismuth subsalicylate. His symptoms resolved and the
      organisms were cleared from his stomach. This study provides evidence that
      another bacterium, a Gastrospirillum, may cause gastritis in man and may be
      transmitted from animal to man.

PMID- 8149840
TI  - Effects of chronic normovolemic anemia on gastric microcirculation and ethanol
      induced gastric damage in rats.
AB  - The effects of chronic normovolemic anemia on gastric microcirculation and
      gastric mucosal susceptibility to ethanol-induced gastric damage were
      investigated in anesthetized rats. Blood exchange by a plasma expander during
      four consecutive days rendered the animals anemic with a 34% decrease in the
      baseline hematocrit but without affecting blood volume. Chronic anemia induced a
      decrease in whole blood viscosity, an increase in gastric mucosal blood flow
      measured by hydrogen gas clearance, a decrease in gastric vascular resistance,
      and a decrease in gastric hemoglobin content without changes in the gastric
      oxygen content, the latter two parameters being measured by reflectance
      spectrophotometry. Gastric mucosal blood flow was lowered by intragastric
      administration of 100% ethanol in both anemic and control rats, but the final
      blood flow was significantly higher in anemic than in control animals.
      Macroscopic gastric damage induced by ethanol administration was significantly
      lower in anemic than in control rats. We conclude that chronic normovolemic
      anemia increases gastric mucosal blood flow and leads a protecting mechanism
      against gastric mucosal damage induced by absolute ethanol.

PMID- 8149841
TI  - Esophageal motility disorders in patients with Sjogren's syndrome.
AB  - Esophageal motility was studied in 21 patients with Sjogren's syndrome, and in 25
      normal volunteers, in order to record the prevalence and type of esophageal motor
      abnormalities. Esophageal motor abnormalities were detected in seven of the 21
      patients (33.3%). These esophageal abnormalities did not correlate with the
      presence of dysphagia, the extraglandular involvement, or the presence of
      autoantibodies.

PMID- 8149842
TI  - Effect of body position on deglutition.
AB  - This study examined the effects of changes in body position on different
      swallowing parameters derived from manofluorographic examinations. Quantitative
      data were obtained in a group of 12 young healthy volunteers. They were all
      tested in the upright position; six of them were also evaluated in the supine
      position, and the other six in the upside down position. In the different
      positions all volunteers were able to swallow a liquid bolus without aspiration
      or stasis. However, the dynamics of the swallow became different. Lying down
      resulted in a pharyngeal transit time comparable with the upright position. The
      tongue driving force was higher and the hypopharyngeal suction power weakened. In
      the upside down position, the pharyngeal transit time became longer and the
      tongue driving force was even more powerful. There was no apparent difference in
      the traditional manometric parameters; the amplitude, duration, and propagation
      velocity of the pharyngeal contraction on swallowing did not change obviously in
      the different body positions.

PMID- 8149843
TI  - Correlation of lower esophageal mucosal ring and lower esophageal sphincter
      pressure.
AB  - We assessed the relationship of lower esophageal sphincter pressure (LESP) to
      presence and absence of lower esophageal mucosal ring (LEMR) in 66 patients to
      determine if the LEMR was more likely related to prolonged sphincter hypotension.
      This potential relationship is of interest because LEMR may be due to reflux
      esophagitis. Each patient had radiographic and manometric studies, and both
      examinations were done within one week of each other. The mean LESP in patients
      with LEMR was 23.8 mm Hg (range 4.2-64 mm Hg) compared to 28.7 mm Hg (range 8-59
      mm Hg) in patients without LEMR; the difference was not statistically
      significant. Patients with LEMR were also divided into three subgroups according
      to the diameter of the rings (< or = 13 mm, 14-19 mm, > or = 20 mm). There was no
      significant relationship between the caliber of LEMR and LESP (P > 0.05).
      Presence of LEMR did not affect the amplitude or duration of primary esophageal
      peristalsis. These results do not support a relationship between LEMR and
      prolonged LESP hypotension or abnormal esophageal motility. However, other
      pathogenetic mechanisms involved in producing reflux esophagitis not related to
      prolonged sphincter hypotension were not studied.

PMID- 8149844
TI  - Vascular compression of the esophagus: a manometric and radiologic study.
AB  - This study was undertaken to determine the prevalence of vascular compression in
      manometric tracings and to determine whether these findings had any clinical
      significance. Vascular compression, defined as a localized area of elevated
      intraesophageal resting pressure > 4 mm Hg with superimposed cyclic pressure
      spikes with a frequency of 60-100/min, was noted in 55 of 241 consecutive
      tracings. The groups with and without vascular compression were similar with
      regard to mean age, sex, and prevalence of dysphagia. Radiographs were available
      for 29 of the 55 and showed compression in 18, but there was no relationship with
      the manometric findings, except for a trend towards finding a positive
      esophagogram with amplitudes > 16 mm Hg. Eleven tracings showed absent
      "relaxation" of this elevation of pressure in response to swallows, and five of
      six available esophagograms showed a corresponding area of compression. We
      conclude that manometric evidence of vascular compression is common and generally
      has no clear relationship with esophagographic findings or dysphagia. However,
      the combined findings of marked increases in pressure and absence of relaxation
      in response to swallows may indicate evidence for a vascular cause of dysphagia.

PMID- 8149845
TI  - Mechanisms and sites of mannitol permeability of small and large intestine in the
      rat.
AB  - Mannitol is commonly used as an intestinal permeability probe, yet the mechanisms
      of its penetration of the intestinal barrier are not entirely clear. Therefore,
      we studied mannitol's permeability of different segments of the intestine and
      studied the kinetics and influence of intraluminal factors on mannitol
      permeability in vivo in perfused intestinal segments of rats. There was linear
      relationship between permeability rate of mannitol and its luminal concentration
      (y = 7.2x + 1.7; r = 0.98), indicating that passive diffusion is involved in
      mannitol's permeability. Increased luminal fluid osmolarity from 0.3 to 0.6
      osmol/liter resulted in decreased net water flux with a corresponding decrease in
      mannitol permeability in both jejunum and colon (P < 0.01), indicating the
      prominent influence of solvent drag on net mannitol permeability. The
      relationship between mannitol permeability and water absorption at different
      osmolarities was linear in the jejunum and colon. At luminal osmolarity of 0.3
      osmol/liter, 34.6% of mannitol permeability was mediated by passive diffusion and
      65.4% was mediated by solvent drag in the jejunum. Mannitol permeability was much
      more dependent on solvent drag in the colon (88.9%) than in the small intestine
      (65.4%). The net permeability rate of mannitol was similar in the jejunum and
      ileum but was much higher in the colon (P < 0.01). Addition of chenodeoxycholate
      (5 mM) to the perfusate resulted in a significant decrease in absorption of water
      (P < 0.01) with a corresponding decrease in mannitol permeability (P < 0.01).
      These studies indicate that mannitol permeability of the intestinal barrier is
      mediated by passive diffusion and solvent drag, with the latter accounting for a
      greater fraction of the total permeability.

PMID- 8149846
TI  - Bile salts determine leukotriene B4 synthesis in a human intestinal cell line
      (CaCo-2).
AB  - The ability of a human colonic epithelial cell line (CaCo-2) to synthesize
      leukotriene B4 (LTB4) in response to bile salt stimulation was examined, as was
      the dependency of such stimulation on the hydrophobic-hydrophilic balance of the
      bile salts. We demonstrate for the first time in this human intestinal epithelial
      cell line the ability of bile salts to stimulate synthesis of LTB4. CaCo-2 cell
      monolayers were incubated with a series of bile salts ranging in concentration
      from 0.5 microM to 1 mM. This resulted in a dose- and hydrophobicity-dependent
      increase in LTB4 synthesis. Hydrophobic bile salts (glycine and taurine
      conjugates of lithocholate and deoxycholate) caused LTB4 synthesis to be
      stimulated 27% and 35%, respectively, above control levels. In contrast,
      hydrophilic bile salts (glycine and taurine conjugates of ursodeoxycholate)
      increased LTB4 synthesis only 11.2% and 16.1%. Under basal conditions
      pretreatment with dexamethasone significantly inhibited bile salt-induced LTB4
      synthesis by 38% compared to control. With more hydrophobic bile salts,
      chenodeoxycholate and deoxycholate, dexamethasone inhibited LTB4 synthesis to
      levels significantly below those observed with dexamethasone under basal
      conditions. Unlike A23187 calcium ionophore-induced LTB4 synthesis, bile salt
      induced stimulation of LTB4 synthesis was not found to be dependent on the
      presence of extracellular calcium. Variations in bile salt stimulation of LTB4 by
      intestinal epithelial cells could be important in modulating cellular responses.
      The synthesis of chemotactic factors, such as LTB4, by the human colonic
      adenocarcinoma epithelial cell line now needs to be extended to normal human
      intestinal epithelium, as it may play a role in many of the functional
      disturbances which characterize intestinal inflammatory conditions.

PMID- 8149847
TI  - Long-term observations on morphological changes of choledochal epithelium after
      choledochoenterostomy in rats.
AB  - Morphological changes of the common bile duct were observed macroscopically and
      microscopically 20 months after choledochojejunostomy and choledochocolonostomy
      in rats. The common bile ducts were remarkably dilated in all rats of both
      experimental models. Choledochal stones consisting of fatty acid calcium and
      calcium bilirubinate were seen in two of six rats with choledochojejunostomy and
      two of five rats with choledochocolonostomy. The main pathological change
      observed in both the groups was remarkable hyperplasia of the choledochal
      epithelium. Only one rat with choledochojejunostomy revealed normal epithelium
      with choledochal stone formation. Intestinal metaplasia was seen in two rats with
      choledochojejunostomy and all with choledochocolonostomy. Squamous
      pseudostratification of the epithelium indicating atypism was observed in two
      rats with choledochojejunostomy. Sialomucin producing cells and sulfomucin
      producing cells were seen in the hyperplastic portion of the epithelium. No
      malignant alteration of the epithelium was detected. These findings indicate that
      long-lasting exposure to digestive enzymes and bacteria causes epithelial
      hyperplasia and further exposure to digestive enzymes plays a major role in
      appearance of the epithelial atypism. Carcinogenesis of the choledochal
      epithelium under such an environment will need much more time to be established.

PMID- 8149848
TI  - "Nonspecific" erosions and ulcers of the colonic mucosa.
AB  - A total of 26 cases of "nonspecific" erosions and ulcers of the colonic mucosa
      are reported. The most common causes were previous abdominal irradiation or
      ischemic disease due to arteriosclerosis. The lesions were localized to all
      segments of the colon. Of the 26 cases, five (19.2%) had erosions (ie, not
      penetrating beyond the muscularis mucosae) and the remaining 21, ulcers (ie,
      penetrating beyond the muscularis mucosae). In seven of the 26 cases (26.9%) more
      than one ulcer was found in the same specimen. Erosions may heal completely by
      epithelial regeneration (ie, restitutio ad integrum) while ulcers usually heal by
      replacing scarring tissue. Thus, the two lesions may not be clinically
      synonymous. The relatively high proportion of erosions among nonspecific
      ulcerations of the colonic mucosa has not been previously pointed out in the
      literature.

PMID- 8149849
TI  - Role of vagal dysfunction in motility and transit disorders of jejunal Roux limb
      after Roux-en-Y gastrojejunostomy.
AB  - After a Roux-en-Y gastrojejunostomy patients frequently complain about abdominal
      pain, fullness, nausea and vomiting, ie, the Roux-en-Y syndrome. Stasis in the
      Roux limb due to disordered motility is known to be a cause of these complaints.
      The aim of the present study was to determine whether vagal denervation
      contributes to the development of motility disturbances and stasis in the Roux
      limb. Forty-seven patients with a Roux-en-Y gastrojejunostomy after partial
      gastrectomy were studied. A truncal vagotomy had been performed in 26 of these 47
      patients. Transit through the Roux limb was evaluated by radionuclide studies,
      motility in the Roux limb was studied by manometry, and vagal function was tested
      by measuring the pancreatic polypeptide response to an insulin-induced
      hypoglycemia (PP test). On the basis of the PP test patients were classified as
      having (1) normal, (2) moderately impaired, and (3) severely impaired vagal
      function. The PP test showed that two of the 26 patients subjected to vagotomy
      had a moderately impaired vagal function, the other 24 all had a severely
      impaired vagal function. In the patients not subjected to a vagotomy, vagal
      function was disturbed in 11 of the 21 patients. Motility disturbances were not
      observed more frequently in patients with either moderately or severely impaired
      vagal function than in patients with normal vagal function. Stasis in the Roux
      limb was seen even more frequently in patients with a normal vagal function than
      in patients with a severely impaired vagal function.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8149850
TI  - Effect of resistant starch on colonic fermentation, bile acid metabolism, and
      mucosal proliferation.
AB  - Resistant starch is by definition that part of starch that escapes digestion in
      the small bowel. Cecal fermentation of resistant starch into short-chain fatty
      acids will result subsequently in a decrease in pH. Thus, resistant starch may
      have the same effect on colonic luminal contents and mucosa as some fiber
      components. We studied the effects of adding 45 g native amylomaize (Hylon-VII)
      to a standardized diet in 14 healthy volunteers on fermentation and colonic
      mucosal proliferation. Hylon-VII is a high amylose maize starch, containing 62%
      resistant starch. During amylomaize consumption, breath hydrogen excretion rose
      85% and fecal short chain fatty acid output increased 35% (P < 0.01). Excretion
      of primary bile acids increased and the soluble deoxycholic acid concentration
      decreased by 50% (P = 0.002). Subsequently, cytotoxicity of the aqueous phase of
      feces--as measured on a colon cancer cell line--decreased (P = 0.007). Colonic
      mucosal proliferation in rectal biopsies (proliferating cell nuclear antigen
      immunostaining) decreased from 6.7 to 5.4% (P = 0.05). We speculate that
      resistant starch consumption decreases colonic mucosal proliferation as a result
      of the decreased formation of cytotoxic secondary bile acids, which is possibly
      mediated through acidification of the large bowel by production of short-chain
      fatty acids.

PMID- 8149851
TI  - Effect of a model of canine jejunoileal orthotopic autotransplantation on jejunal
      and ileal transport of water and electrolytes.
AB  - Canine jejunoileal transplantation induces an early profuse watery diarrhea of
      uncertain etiology. Our aim was to determine the temporal effects of a canine
      model of jejunoileal autotransplantation (a model devoid of confounding effects
      of ischemia-reperfusion or immune rejection) on basal jejunal and ileal
      absorption of water and electrolytes to determine if impaired absorption is
      responsible for the diarrhea. Our hypothesis was that net absorption of water and
      electrolytes in an enterically isolated loop would decrease after jejunoileal
      transplantation. Four groups of dogs (N > or = 6) were prepared with 80-cm
      modified Thiry-Vella loops: group I, neurally intact jejunum; group II,
      autotransplanted jejunum; group III, neurally intact ileum; and group IV,
      autotransplanted ileum. The loops were perfused for 3 hr with 150 mM NaCl at 3
      ml/min under fasted conditions; transit time through the loop was determined by
      bolus of a nonabsorbable marker. Dogs were studied on three separate days at one,
      two, eight, and nine weeks postoperatively. Net absorptive fluxes of water and
      electrolytes and transit times were similar (P > 0.05) between neurally intact
      and autotransplant groups (group I vs II and group III vs IV) at each time point.
      Ileal loops absorbed more than jejunal loops, and transit was slower in ileal
      loops (each P < 0.05). Our findings suggest that, despite the obligate disruption
      of extrinsic innervation, enteric (intrinsic) neural continuity, and lymphatic
      drainage that accompanies this canine model of jejunoileal autotransplantation,
      net basal absorptive function of water and electrolytes during the fasted state
      was not decreased nor was transit altered either in jejunum or ileum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8149852
TI  - Fat-storing cell abnormalities associated with endothelial cell damage after cold
      ischemic storage of rat liver in UW solution.
AB  - Rat liver was stored at 1 degree C in University of Wisconsin solution, and
      morphological changes were observed after 12, 18, 24, and 36 hr by transmission
      electron microscopy. There were two types of endothelial cell damage in the
      hepatic sinusoids. One was disruption of the endothelial linings, and the other
      detachment of endothelial cells into the sinusoidal space accompanied by fat
      storing cell abnormalities. The former damage was seen after storage longer than
      12 hr, while the latter developed after 18 hr even in the hepatic sinusoids with
      no disruption of the linings. Considering that fat-storing cell damage can
      produce endothelial cell destruction, this damage should be given attention as
      one of factors of endothelial cell destruction in the hepatic sinusoids after
      cold storage of the liver.

PMID- 8149853
TI  - Glutathione and ATP levels, subcellular distribution of enzymes, and permeability
      of duct system in rabbit pancreas following intravenous administration of alcohol
      and cerulein.
AB  - In order to reproduce what might occur during the initial phase in some cases of
      acute alcohol-induced pancreatitis, rabbits were infused with diluted ethanol and
      low-dose cerulein. The duct permeability was assessed by recovery of
      fluoresceinated dextran (molecular weight 19,500) in central venous blood
      following orthograde duct perfusion with this substance in the anesthetized
      animal. Serum ethanol, lipase, and amylase were measured; pancreatic duct
      morphology was examined by light microscopy and electron microscopy. ATP and
      glutathione were measured, as were amylase, trypsinogen/trypsin, cathepsin B, and
      DNA levels in differential centrifugates. As expected, acinar amylase and
      trypsinogen showed a significant decrease in the experimental group; cathepsin B
      activity was similarly diminished. Compared with the control group, the activity
      of serum amylase and lipase in the experimental group demonstrated a significant
      increase. However, no differences between saline-infused control animals and the
      treated group regarding pancreatic duct permeability, continuity of lumen-lining
      epithelium, ATP and glutathione levels, and the relative subcellular distribution
      of pancreatic digestive and lysosomal enzymes were observed. Thus, our findings
      do not support the relevance of some of the most common hypotheses on the
      pathophysiology of acute pancreatitis in its early stage for at least a certain
      subgroup of patients with acute alcohol-induced pancreatitis.

PMID- 8149854
TI  - Crohn's disease and cystic fibrosis.
AB  - Advances in investigative techniques have led to increasing reports of Crohn's
      disease in CF patients. A retrospective review of the literature on IBD in CF
      showed findings characterized by ileocolitis with fistula formation; 83% required
      surgery. A prospective survey of 11,321 CF patients attending 49 CF centers
      revealed 28 with IBD (25 Crohn's, three ulcerative colitis), ages 4-20 years,
      mean 15.6 years. The prevalence rate of IBD (247/10(5)) was 7x controls and was
      accounted for by Crohn's disease (221/10(5)) which was 17x controls. The
      mechanisms that predispose CF patients to Crohn's disease are discussed.

PMID- 8149855
TI  - Anti-neutrophil cytoplasmic antibodies (ANCA) and inflammatory bowel diseases in
      Chinese.
AB  - Inflammatory bowel diseases are uncommon in the Chinese, but the incidence is
      rising. Their differentiation from infective colitis is often not clear-cut and
      diagnosing inflammatory bowel diseases can be difficult in Asia. We have studied
      Chinese patients with ulcerative colitis (N = 19) and Crohn's disease (N = 12)
      for anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence
      (IIF) and enzyme-linked immunosorbent assays (ELISA). Patients with enteric fever
      (N = 29) and irritable bowel syndrome (N = 24) were recruited as controls.
      Seventy-three percent of ulcerative colitis patients exhibited either p-ANCA
      (31%) or c-ANCA (42%) by IIF. Twenty-five percent of Crohn's disease patients
      were found to be p-ANCA positive. However, these ANCA were nonreactive to anti
      alpha granule, antiproteinase 3, antimyeloperoxidase, or antilactoferrin. All
      positive patients had extensive colitis. Sera collected from patients suffering
      from enteric fever and irritable bowel syndrome were negative for ANCA by IIF and
      ELISA. We concluded that the detection of ANCA is helpful in diagnosing
      inflammatory bowel diseases. Further attempts to characterize these
      autoantibodies are needed.

PMID- 8149856
TI  - Prostaglandins mediate fish oil protection against ethanol-induced gastric
      mucosal injury in rats.

PMID- 8149857
TI  - Interference by lubricating jelly in ELISA assay for pepsin in gastric juice
      samples.

PMID- 8149858
TI  - Response to Dr. Peterson:.

PMID- 8149859
TI  - Cosmetics expert Dr. Ron Goldstein shows how working together works. Interview by
      Cathy Jameson.

PMID- 8149860
TI  - Exploring health care reform.

PMID- 8149861
TI  - Keeping the appointment book full.

PMID- 8149862
TI  - A look at oral cancer lesions: prevention, early detection keys to survival.

PMID- 8149864
TI  - Letting out a laugh; the value of workplace humor.

PMID- 8149863
TI  - The oral effects of AIDS.

PMID- 8149865
TI  - Carpal tunnel syndrome.

PMID- 8149866
TI  - Working with the dental laboratory.

PMID- 8149867
TI  - Putting function and esthetics together.

PMID- 8149868
TI  - Pharmacokinetic assessment of the dermal absorption of N,N-diethyl-m-toluamide
      (DEET) in cattle.
AB  - Model-independent pharmacokinetic methods based on statistical moments were
      applied to investigate the plasma disposition characteristics of N,N-diethyl-m
      toluamide (DEET insect repellent) after single-dose treatment of experimental
      cattle by rapid intravenous injection (2.5-2.7 mg/kg) and by dermal application
      (10 mg/kg) to the back. DEET was determined in jugular blood samples by capillary
      GC with a nitrogen-selective detector and an internal standard of N,N-dipropyl-m
      toluamide. Using weighted least squares linear regression analysis, the assay was
      validated over the concentration range of 19-1910 ng/ml of plasma. Comparison of
      areas under the plasma concentration-time curves after intravenous and dermal
      treatments of four Hereford heifers indicated that 72.9 +/- 8.3% (mean +/- SD) of
      the dermally applied dose was absorbed into the systemic circulation. The time-to
      peak plasma concentrations following dermal treatments was 37.5 +/- 8.7 min.
      Apparent elimination rate constants were not significantly different between the
      two routes of administration. Linear pharmacokinetics was demonstrated with four
      additional cattle by comparing systemic clearance after intravenous infusion to
      steady-state plasma levels of approximately 0.5 and 2.5 micrograms/ml. The rapid
      and extensive dermal absorption of DEET observed in this study will probably
      contribute to a short duration of insect repellent action if ethanol-based sprays
      are used to protect cattle under field conditions.

PMID- 8149869
TI  - Disposition and protein binding of valproic acid in the developing rat.
AB  - The disposition of valproic acid (VPA) in serum and brain tissue was examined in
      developing rats (5, 10, 20, and 60 days postpartum) following both single and
      multiple intraperitoneal doses of VPA. The binding of VPA to proteins in serum
      was determined ex vivo by ultrafiltration for each age group in pooled serum at
      various time points following VPA administration, as well as after in vitro
      addition of VPA (8-2400 micrograms/ml) to pooled rat serum from naive animals of
      each age. Concentration-time data for VPA in serum and brain tissue were fit
      simultaneously, assuming first-order absorption from the peritoneal injection
      site and first-order transfer of drug between serum and brain tissue. Kinetic
      analysis revealed that total clearance increased with postnatal age, whereas the
      volume of distribution and brain-to-serum partitioning of VPA decreased during
      development. Furthermore, enterohepatic recirculation, a well-described facet of
      VPA disposition in adult rats, was not evident from examination of the serum
      concentration-time profile in animals prior to the time of weaning. A progressive
      increase in the binding of VPA to proteins in serum was observed during postnatal
      development. The bound fraction determined ex vivo was less than that determined
      in vitro for all age groups, suggesting the possibility of competition for VPA
      binding sites by metabolite(s) formed in vivo.

PMID- 8149870
TI  - Site-dependent intestinal hydrolysis of valproate and morphine glucuronide in the
      developing rat.
AB  - A previous pharmacokinetic study in developing rats suggested that enterohepatic
      recirculation of valproic acid was absent prior to weaning. One explanation for
      this observation is that the rate, extent, and/or primary site of glucuronide
      hydrolysis in the gastrointestinal tract changes during postnatal development. To
      test this hypothesis, the hydrolysis of two model glucuronide conjugates,
      valproate glucuronide and morphine-3-beta,D-glucuronide, was examined in vitro in
      homogenates of small and large intestine obtained from rats at 5-60 days
      postpartum. Analysis of initial hydrolysis rates indicated that the principal
      hydrolytic site for both glucuronide conjugates shifted from the upper to lower
      intestine as the animals developed. The initial hydrolysis rate (nmol/min/g) for
      valproate glucuronide decreased from 38.1 +/- 10.2 to 8.25 +/- 2.42 in the small
      intestine, and increased from 14.2 +/- 2.3 to 105 +/- 22 in the large intestine,
      as rats developed from 5 to 60 days postpartum, respectively. Likewise, the
      intestinal hydrolysis rate for morphine-3-beta,D-glucuronide decreased from 3.70
      +/- 0.46 to 0.646 +/- 0.165 in the small intestine, and increased from 3.50 +/-
      0.48 to 115 +/- 30 in the large intestine, as rats developed from 5 to 60 days
      postpartum, respectively. If hydrolysis occurs immediately after excretion of
      conjugate into the intestine in neonatal rats, minimal temporal delay between
      excretion of conjugate and reabsorption of liberated parent may occur, therefore
      concealing the secondary increase in serum drug concentrations associated with
      enterohepatic recirculation. In contrast, the time required for conjugates to
      reach the primary hydrolytic site in adult animals is sufficient for appearance
      of secondary peaks in the serum drug concentration-time profile.

PMID- 8149871
TI  - Use of rat and human in vitro systems to assess the effectiveness and enzymology
      of deoxy-guanine analogues as prodrugs of an antiviral agent.
AB  - BRL 55792, BRL 55791, and BRL 55039 are prodrugs of an active anti-viral agent 9
      (3-hydroxypropoxy) guanine, (BRL 44385). The prodrugs were 6-deoxygenated
      analogues of BRL 44385 with ether groups substituted at the 9-position: BRL 55792
      with an (isopropoxymethyloxy)propoxy group, BRL 55791 with a
      (methoxymethyloxy)propoxy group, and BRL 55039 with an ethoxypropoxy group.
      Conversion of the prodrugs to BRL 44385 had been demonstrated in vivo in rat and
      involved 6-oxidation followed by dealkylation. Metabolism was studied in rat
      liver in vitro systems to find a model to evaluate BRL 44385 production. Rat
      hepatocytes performed both reaction steps and were used to assess which of the
      three prodrugs demonstrated greatest production of the active drug. BRL 55792
      demonstrated greatest conversion in vitro and this was in agreement with in vivo
      data. The production of BRL 44385 from BRL 55792 was also demonstrated in human
      hepatocyte incubations providing evidence that these reactions can occur in man
      thereby increasing confidence that BRL 55792 would be a suitable prodrug for
      human therapy. Further experiments were performed to investigate the enzymes
      involved in these conversions. The 6-oxidation step occurred in the cytosol. Use
      of allopurinol and menadione (xanthine and aldehyde oxidase inhibitors) indicated
      that these conversions were catalyzed exclusively by xanthine oxidase in the rat
      but mainly by aldehyde oxidase in man. The dealkylation reaction was detected in
      hepatocytes but not in homogenates or subcellular fractions. Inhibition of this
      reaction by aminobenzotriazole and ketoconazole (P-450 inhibitors) indicated that
      it was mediated by cytochrome P-450.

PMID- 8149872
TI  - Metabolic disposition of simvastatin in patients with T-tube drainage.
AB  - A study to investigate the disposition and biliary excretion of simvastatin (SV)
      was conducted in four cholecystectomy patients with T-tube drainage. Each patient
      received a single oral dose of 100 mg of [14C]SV (20 microCi). Of the 14C-labeled
      dose, approximately 35% was excreted in urine, 25% in bile, and 20% in feces.
      Thus, at least 60% of the oral dose was absorbed from the gastrointestinal tract.
      Of the AUC for radioactivity in plasma, 13% was contributed by the HMG-CoA
      reductase inhibitors. In addition, only 2% of the 14C-dose was eliminated in
      urine as HMG-CoA reductase inhibitors. Thus, most of the SV-related compounds in
      plasma and urine have little or no HMG-CoA reductase inhibitory activity. The
      same is probably true for these compounds in bile. Two major active metabolites
      were present in the bile. Based on HPLC and MS/MS data, they were identified as
      6' beta-COOH-SVA and 6'-OH-SVA. In general, the majority of the radioactivity in
      the bile and urine was excreted within 24 hr postdose. Of the radioactivity
      excreted in the 0- to 24-hr bile, on average, approximately 30% was contributed
      by 6' beta-COOH-SVA and 6'-OH-SVA. These two metabolites accounted for the
      majority of HMG-CoA reductase inhibitory activity in the bile. Little or SV or no
      SVA was present in the bile.

PMID- 8149873
TI  - Codeine toxicokinetics in rats during a two-year dosed feed study.
AB  - Codeine toxicokinetics in F344 rats of both sexes were determined during a 2-year
      chronic toxicology study using dosed feed as the exposure route with a 12-hr
      light/dark cycle starting at 7:00 a.m. Rats were allowed to access to dosed feed
      formulations ad libitum with codeine concentrations at 0, 400, 800, and 1600 ppm.
      Blood samples were collected from individual rat on days 7, 21, and 90 at 7:00
      p.m., 11:00 p.m., 3:00 a.m., and 7:00 a.m. Additional samples were collected at
      16 and 24 months between 6:00-8:00 a.m. Plasma concentrations of codeine and
      morphine were determined directly by radioimmunoassay. Concentrations of their
      conjugates were determined indirectly by measuring the total amount of free
      codeine and morphine released after samples were treated with beta-glucuronidase.
      Results indicated that plasma concentrations of both codeine and morphine
      steadily decreased from day 7 to 16 months and then rebounded at 24 months.
      Results also indicated that plasma concentrations of both codeine and morphine
      correlated well with the amounts of codeine added to the feed. Bioavailability of
      codeine using the dosed feed route increased with dose, varying from 10% to 25%,
      which was somewhat higher than the previously reported approximately 8%
      bioavailability using the gavage route. Concentrations of conjugated codeine were
      very low, whereas concentrations of conjugated morphine were very high. These
      results suggested that demethylation of codeine to morphine in rats is the main
      metabolic pathway and was maintained over the course of the study.

PMID- 8149874
TI  - Glutathione-dependent biosynthesis and bioactivation of S-(1,2
      dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine, the glutathione
      and cysteine S-conjugates of dichloroacetylene, in rat tissues and subcellular
      fractions.
AB  - Dichloroacetylene is neurotoxic, nephrotoxic, and nephrocarcinogenic. The present
      experiments were designed to test further the hypothesis that the glutathione
      conjugate of dichloroacetylene, S-(1,2-dichlorovinyl)glutathione (DCVG), may be
      involved in dichloroacetylene-induced neurotoxicity. Hence, the biosynthesis of
      DCVG from dichloroacetylene and glutathione was studied in cytosolic, microsomal,
      and mitochondrial fractions of liver, lung, brain, and kidney. Enzymatic
      formation of DCVG was observed in liver microsomes and mitochondria, but only
      nonenzymatic formation of DCVG was seen in lung, brain, and kidney. The KM and
      Vmax for DCVG biosynthesis with glutathione as the variable substrate were 0.40
      +/- 0.28 mM and 487 +/- 90.3 nmol/mg protein/min, respectively. No region
      specific differences in the rates of DCVG biosynthesis in the brain were
      observed. In whole brain homogenates, DCVG was hydrolyzed to DCVC, which was
      biotransformed to pyruvate and S-(1,2-dichlorovinyl)-3- mercaptopyruvate,
      indicating cysteine conjugate beta-lyase-catalyzed beta-elimination and
      transamination reactions in cerebellar tissues. These findings indicate that the
      glutathione-dependent bioactivation of dichloroacetylene may be involved in the
      dichloroacetylene-induced neurotoxicity.

PMID- 8149875
TI  - Renal tubular transport of cimetidine in the isolated perfused kidney of the rat.
AB  - The renal handling of cimetidine (pKa = 6.8) was studied in the isolated perfused
      rat kidney (IPK). Concentrations in the therapeutic range (< 10 micrograms/ml)
      had little adverse effects on the functional parameters of the IPK, and even a
      concentration of 250 micrograms/ml still had only minor effects. When initial
      perfusate concentrations were low (< 2.5 micrograms/ml), the ratio of renal
      clearance over filtered amount (CLR/GF) was approximately 3, indicating net
      tubular secretion. CLR/GF decreased at increasing perfusate concentrations, and
      above 25 micrograms/ml, there was progressive net reabsorption (CLR/GF < 1).
      CLR/GF was highly dependent on variations in urine flow and pH, which is
      indicative of substantial tubular reabsorption by nonionic diffusion. A kinetic
      model was used to describe the renal handling of cimetidine. This model
      incorporates the variables influencing the clearance of cimetidine, like urine
      flow, glomerular filtration rate, and urine pH. Cimetidine was subject to active
      tubular secretion following Michaelis-Menten kinetics and passive tubular
      reabsorption of the unionized fraction. The constant for reabsorption was 197 +/-
      40 microliters/min, the Michaelis-Menten constant for tubular secretion was 0.2
      +/- 0.1 microgram/ml, and the maximum transport capacity was 1.3 +/- 0.3
      microgram/min. Cimetidine did not accumulate in IPK, with kidney to perfusate
      ratios of approximately 2. In conclusion, the renal handling of cimetidine in the
      IPK is concentration-dependent and is determined by glomerular filtration, active
      tubular secretion, and a substantial flow- and pH-dependent passive reabsorption.

PMID- 8149876
TI  - Pharmacokinetics of 13-cis-, all-trans-, 13-cis-4-oxo-, and all-trans-4-oxo
      retinoic acid after intravenous administration in the cynomolgus monkey.
AB  - The intravenous pharmacokinetics of 13-cis-, all-trans-, 13-cis-4-oxo, and all
      trans-4-oxo retinoic acid (RA) were determined in nonpregnant female cynomolgus
      monkeys. All-trans- and 13-cis-RA were injected at two doses (0.25 or 0.0125
      mg/kg) and all-trans-4-oxo RA and 13-cis-4-oxo RA at 0.25 mg/kg. Total body
      clearance, volume of distribution, and volume of distribution at steady state of
      all-trans-RA were dose-dependent with greater values at the lower dose.
      Elimination half-life was longer for the cis-compounds and not dose-dependent (N
      = 1 for 13-cis-4-oxo RA, N = 3 for other compounds, harmonic mean +/-
      pseudostandard deviation, min): 13-cis-4-oxo RA (837) > or = 13-cis-RA (301 +/-
      204) > all-trans-RA (38 +/- 3) > all-trans-4-oxo RA (11 +/- 2). Secondary plasma
      peaks were noted only after administration of 13-cis-4-oxo RA. The low area under
      the time concentration curves for observable metabolites after intravenous
      injection of the oxidated compounds suggests further metabolism plays a minimal
      role in the elimination of these compounds from the monkey. Plasma-time
      concentration curves were fitted to multicompartmental models and suggested < 30%
      of each compound was available in the central compartment for elimination in the
      postdistribution phase. A comparison of the kinetics of the isomers indicated
      oxidation of all-trans-RA to all-trans-4-oxo RA increased mean total body
      clearance values 4-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149877
TI  - Monoacetyldapsone inhibition of dapsone N-hydroxylation by human and rat liver
      microsomes.
AB  - Dapsone (DDS) is metabolized by N-hydroxylation and N-acetylation to DDS
      hydroxylamine (DDS-NOH) and monoacetyldapsone (MAD), respectively. The activities
      of these two alternative and independent reactions vary widely between
      individuals and show an inverse relationship during chronic DDS therapy. Toxicity
      observed during DDS therapy has been attributed to DDS-NOH. The observation of
      reduced toxicity in rapid acetylators, who are also poor hydroxylators,
      therefore, raised the possibility that MAD may be inhibiting DDS-NOH formation.
      This hypothesis was tested in human and rat liver microsomes. Human liver
      microsomes hydroxylated DDS with a lower affinity (KM 2-fold greater) and lower
      maximal catalytic activity (Vmax 12-fold lower) than that of the rat. The
      relative catalytic activity (Vmax/KM) was 22-fold higher in rat compared with
      human liver microsomes. Furthermore, MAD was a potent inhibitor of DDS N
      hydroxylation by rat liver microsomes (52% inhibition at 0.01 mM MAD) compared
      with human liver microsomes (23% inhibition at 0.4 mM MAD). Human, but not rat,
      liver microsomes deacetylated MAD to DDS by an NADPH independent mechanism. These
      results show that substantial differences exist in DDS N-hydroxylase between rats
      and humans, with respect to substrate affinity, enzyme activity, and
      susceptibility to inhibition, such that information obtained from the rat should
      not be extrapolated to humans. We conclude that MAD is a potent inhibitor of DDS
      NOH formation in rat liver microsomes. The degree of inhibition in human
      microsomes, however, suggest that MAD is unlikely to be a significant modulator
      of enzyme activity in vivo.

PMID- 8149878
TI  - Influence of phenobarbital induction on the enantioselective N-dechloroethylation
      of ifosfamide enantiomers in the rat.

PMID- 8149879
TI  - Drug concentrations in human brain tissue samples from epileptic patients treated
      with felbamate.

PMID- 8149880
TI  - Isolation and identification of the major urinary metabolite of m
      chlorophenylpiperazine in the rat.

PMID- 8149881
TI  - Distribution and excretion of 125I-ardeparin, a low molecular weight heparin, in
      rats and beagle dogs.

PMID- 8149882
TI  - Interaction of cimetidine with oxidized and prereduced microsomal cytochrome P
      450.

PMID- 8149883
TI  - Pharmacokinetic analysis of enterohepatic circulation of buprenorphine and its
      active metabolite, norbuprenorphine, in rats.
AB  - The pharmacokinetic characteristics of buprenorphine (BN) and its active
      metabolite, norbuprenorphine (NBN), was investigated using rats. The elimination
      half-life (t1/2), total body clearance (CLtot), and steady-state volume of
      distribution (Vdss) of BN (0.6 mg/kg iv dose) in the intact rat were 2.8 hr, 23.3
      ml/min/kg, and 4.2 liters/kg, respectively, and those of NBN (0.6 mg/kg iv dose)
      were 0.9 hr, 35.0 ml/min/kg, and 2.0 liters/kg. Within 24 hr after administration
      of BN (0.6 mg/kg dose) to the bile-fistula rat, 74.1% of dose was excreted in the
      bile as BN glucuronide (BN-Glu) and 18.5% as NBN glucuronide (NBN-Glu), and in
      urine < 3.2% as BN-Glu. After administration of NBN to the bile-fistula rat,
      85.1% and 9.1% of the dose were excreted as NGN-Glu in bile and urine,
      respectively. The existence of the enterohepatic circulation (EHC) of BN and NBN
      was confirmed by using paired rats: the donor and recipient rats. Within 24 hr
      after administration of BN (0.6 mg/kg dose) to the donor rat, 58.8% of the dose
      was reexcreted as NBN-Glu in bile of the recipient and 25.1% as BN-Glu. Based on
      the results of in vitro metabolism, it was suggested that this increase in the
      proportion of NBN-Glu in bile observed after one enterohepatic cycling of BN may
      be due to the first-pass metabolism in the liver. BN was detected in the plasma
      of the recipient rat after administration of BN, to the donor rat.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8149884
TI  - Tissue distribution and metabolism of amitriptyline after repeated administration
      in rats.
AB  - Plasma concentration, tissue distribution, and metabolism of amitriptyline (AMI)
      in rats pretreated with AMI (20 mg/kg/day, ip dose, for 7 days; treated) were
      compared with control rats. Plasma concentrations of AMI after intravenous
      administration (2 and 10 mg/kg) to the treated rat were significantly higher than
      those to the control rat in both doses. The difference in the plasma
      concentration between both groups may be caused by a change of tissue
      distribution of AMI, because the blood cell-to-plasma concentration ratio and the
      tissue-to-blood concentration ratio values for various tissues in the treated rat
      were smaller than those in the control, respectively. The plasma unbound fraction
      of AMI in the treated rat was significantly smaller (p < 0.05). alpha 1-Acid
      glycoprotein concentration in plasma of the treated rat was approximately twice
      that in the control rat. These results suggest that the decrease of tissue
      distribution of AMI in the treated rat may be caused by the decrease in the
      plasma unbound fraction of AMI with the increase of alpha 1-acid glycoprotein in
      plasma. The area under the plasma concentration-time curve for AMI and its main
      metabolite, nortriptyline, in the treated rat after intraportal administration of
      AMI was 1/3 and 3-fold those in the control rats, respectively. On the other
      hand, the hepatic intrinsic clearance (CLH,Int) of the unbound drug in the
      treated rat was approximately twice that of the control, suggesting that the
      increase of the (CLH,Int) by repeated administration of AMI may result in the
      induction of oxidative metabolism.

PMID- 8149885
TI  - Kinetics of tissue distribution and elimination of retinoid drugs in the rat. I.
      Acitretin.
AB  - Rats were injected with single intravenous doses of acitretin (6 mg/kg), and
      concentrations of the drug and its metabolite, 13-cis-acitretin, were determined
      in plasma and nine tissues up to 6 hr postdose. A newly developed sensitive
      method for the determination by HPLC of acitretin, 13-cis-acitretin, and
      etretinate was used. Acitretin rapidly appeared in liver and muscle, where it
      underwent redistribution into skin and adipose tissue. Tissue/plasma
      concentration ratios of acitretin ranged from 2.8 to 0.3 in the order adipose
      tissue > brain, liver > lung, heart, kidney, spleen > skin, muscle. Adipose
      tissue storage was moderate and short-lived. The metabolite, 13-cis-acitretin,
      was detected in all tissues but not in plasma; it accounted for < 10% of the
      administered dose at any time. No etretinate could be detected as a metabolite in
      plasma or tissues. After 6 hr, < 1% of the dose remained in the body as acitretin
      and 13-cis-acitretin. Disappearance was monophasic, with an elimination half-life
      of 70 min in plasma and 68 +/- 9 min in the nine tissues. The volume of
      distribution was 0.6 liters/kg and clearance 6 ml.min-1.kg-1. Acitretin was
      characterized by rapid first-order elimination and the absence of storage in a
      deep compartment.

PMID- 8149886
TI  - Kinetics of tissue distribution and elimination of retinoid drugs in the rat. II.
      Etretinate.
AB  - Rats were injected with single intravenous doses of etretinate (6 mg/kg), and
      concentrations of the drug and its metabolites, acitretin and 13-cis-acitretin,
      were determined in plasma and nine tissues up to 96 hr. A newly developed
      sensitive method for the determination by HPLC of the three retinoids in tissues
      was used. Etretinate rapidly appeared in most tissues and underwent a
      redistribution from highly perfused organs into muscle, skin, and ultimately,
      adipose tissue. Tissue/plasma concentration ratios ranged from 14 to 1, with the
      highest value in adipose tissue. In this tissue, maximum concentration was
      reached after 1.5 hr and remained practically constant up to 96 hr. Etretinate
      was rapidly hydrolyzed to form acitretin at concentrations that surpassed those
      of the parent drug in plasma, liver, kidney, and brain. After 6 hr, approximately
      45% of etretinate had been metabolized to acitretin and approximately 40% to
      unidentified metabolites. These metabolites were not observed in tissues after 6
      hr postdose. The parent drug was not observed 12 hr postdose, except for 6% of
      the dose remaining in adipose tissue. Etretinate elimination, in most tissues,
      was biphasic with terminal half-lives of 41 hr in skin, 1-6 hr in other lean
      tissues, and 1.7 hr in plasma. A volume of distribution of 1.7 liters/kg was
      determined, and a clearance of 12 ml.min-1.kg-1. Etretinate is characterized by
      rapid metabolism, transient storage in skin, and prolonged storage at a low level
      in adipose tissue as a deep compartment. A comparison of the pharmacokinetics of
      the closely related retinoids, etretinate and acitretin, disclose very pronounced
      differences.

PMID- 8149887
TI  - Mechanisms of time-dependent kinetics of diltiazem in the isolated perfused rat
      liver.
AB  - The time-dependent mechanisms of diltiazem (DZ) disposition were studied in a
      single-pass isolated perfused rat liver system. DZ (2-100 microM) was infused
      continuously until a steady state was achieved. The time required to achieve
      steady state (Tss) ranged from 15 to 75 min and was inversely related to infusion
      concentration. Steady-state extraction (E) of DZ decreased from 0.98 to 0.73 as
      the outlet concentration increased from 0.03 to 26.34 microM. This reduction of E
      is not related to the saturation of the primary deacetylation and N-demethylation
      pathways of metabolism. The N-demethylated metabolite went through a
      characteristic maximum prior to reaching a steady state, indicating enzyme
      inactivation. During a second DZ infusion, spaced with a 30-min washout period
      (stop-infusion experiment), the concentration vs. time profile of DZ was similar
      to that of the first one. Washout data from stop-infusion and [3H]DZ infusion
      studies showed that DZ and its metabolites were tightly bound to liver proteins.
      This observation is consistent with the unusually long Tss of DZ. Infusion
      studies with [3H]DZ showed that 669.5 +/- 156.5 and 974.2 +/- 99.2 nmol of DZ and
      its metabolites (calculated as DZ) were bound and/or distributed/g of liver at
      inlet concentrations of 35.5 +/- 3.2 and 67.2 +/- 3.4 microM, respectively. The
      amounts of DZ and its metabolites bound irreversibly to the whole liver, hepatic
      microsomal and hepatic cytosolic proteins were not different at the two inlet
      concentrations studied and were 24.5 +/- 6.6, 48.8 +/- 11.8, and 23.7 +/- 5.8
      pmol/mg of protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149888
TI  - Suppression of in vivo clearance of N-nitrosodimethylamine in mice by cotreatment
      with ethanol.
AB  - Oral cotreatment of mice with ethanol results in increased tumors in extrahepatic
      organs caused by some nitrosamines. This action, attributed in part to inhibition
      of hepatic first-pass carcinogen metabolism by ethanol, has possible relevance to
      the enhancing effect of alcoholic beverage consumption on human cancer risk. In
      this study, the effects of ethanol on clearance of N-nitrosodimethylamine (NDMA)
      were quantified in Swiss female and strain A male mice. In Swiss mice, a 1.6 g/kg
      ig ethanol dose preceding 1 or 5 mg/kg iv NDMA resulted in 20- to 30-fold
      increases in area-under-the-blood-concentration-vs.-time curves, mean residence
      times, and clearance half-times, and similar decreases in clearance. For a 0.5
      mg/kg ig NDMA dose, the pharmacokinetic parameters were altered 30-fold and 450
      fold by simultaneous ethanol doses of 0.08 and 0.8 g/kg, respectively. With 5 mg
      NDMA/kg ig, 0.4, 0.8, and 1.6 g/kg ethanol resulted in 6-, 10-, and 20-fold
      changes in clearance parameters. Comparison of the data with results obtained
      previously with patas monkeys indicated comparable effects of ethanol on tissue
      exposure to NDMA in the two species, confirming potential human applicability. In
      experiments with strain A mice, NDMA concentrations were also monitored in lung
      and liver. NDMA amounts in lung paralleled those in blood, and were more than
      sufficient to account for the previously reported increases in DNA adducts and
      tumors in lungs of similarly treated strain A mice.

PMID- 8149889
TI  - Linear relationship between GABAA receptor occupancy of muscimol and glucose
      metabolic response in the conscious mouse brain. Clinical implication based on
      comparison with benzodiazepine receptor agonist.
AB  - The effect of muscimol, a GABAA receptor agonist, on the basic metabolic activity
      was investigated in the mouse brain and was correlated with its receptor
      occupancy. For the quantitative evaluation of the functional activity of the
      mouse brain, the cerebral glucose utilization was measured by the double tracer
      technique, using [14C] 2-deoxyglucose and [3H]3-O-methylglucose. The dose
      dependent reduction in the cerebral glucose utilization was observed after
      intravenous administration of various doses of muscimol (0.3-1.5 mg/kg). On the
      other hand, the GABAA receptor occupancy of muscimol was determined by using the
      values of the unbound drug concentration in the brain tissue and the receptor
      dissociation constant based on the in vitro binding experiments using the
      dissociated brain cells. The tissue unbound concentration of muscimol was
      calculated by multiplying the total concentration in the brain after
      administration of muscimol and the tissue unbound fraction, which was measured by
      the equilibrium dialysis method using brain tissue homogenate. A linear
      relationship was observed between the GABAA receptor occupancy of muscimol and
      the decrease in the cerebral glucose utilization. This finding indicates that the
      simple receptor occupancy theory holds for this receptor-ligand system, and there
      is a large difference in the effect on glucose metabolic response between GABAA
      receptor-agonist interaction and benzodiazepine receptor-agonist interaction.

PMID- 8149890
TI  - Metabolic fate and pharmacokinetics of the acyclovir prodrug valaciclovir in
      cynomolgus monkeys.
AB  - Valaciclovir, the L-valyl ester of acyclovir (ZOVIRAX), demonstrated good oral
      absorption and nearly complete conversion to acyclovir in cynomolgus monkeys,
      indicating its suitability as an orally administered prodrug. The major urinary
      metabolites of [8-14C]valaciclovir, administered orally (10 and 25 mg/kg) or
      intravenously (10 mg/kg) to male monkeys, were acyclovir (46%-59% of urinary
      radioactivity), 8-hydroxyacyclovir (25%-30%), and 9-(carboxymethoxymethyl)guanine
      (CMMG) (11%-12%). Following oral and intravenous dosing, intact prodrug accounted
      for only 0.5% and 6% of urinary radioactivity, respectively. Dose-independent
      kinetics were observed for acyclovir derived from orally administered [8
      14C]valaciclovir at the 10 and 25 mg/kg dose levels, with both AUC (24 and 60
      microM.hr, respectively) and Cmax (8 and 23 microM, respectively) increasing
      nearly in proportion to the dose. Acyclovir was present in plasma at all sampling
      times (5 min to 7 hr postdose) after both oral doses, whereas the prodrug was not
      detected following either oral dose. The elimination of acyclovir after oral
      administration was monophasic, with an apparent half-life of 1.3-1.5 hr. Similar
      to acyclovir, both 8-hydroxyacyclovir and CMMG demonstrated dose-independent
      kinetics with apparent elimination half-lives of 1-1.6 hr. Intravenously
      administered [8-14C]valaciclovir (10 mg/kg) was rapidly converted to acyclovir,
      with the elimination half-life of acyclovir (0.9 hr) being 1.5-fold that of the
      prodrug (0.6 hr). The oral bioavailability of acyclovir derived from valaciclovir
      in cynomolgus monkey was 67 +/- 13%, representing a significant improvement over
      the limited bioavailability after acyclovir administration to primates.

PMID- 8149891
TI  - Metabolic disposition of the acyclovir prodrug valaciclovir in the rat.
AB  - The prodrug valaciclovir demonstrated good oral absorption, rapid distribution
      and elimination, and extensive biotransformation to acyclovir in male CD rats.
      The mean urinary excretion of radioactivity following oral and intravenous
      administration of [8-14C]valaciclovir (25 mg/kg) was 65% and 95% of the dose,
      respectively. Acyclovir was the predominant radiolabeled urinary metabolite
      accounting for 57% and 65% of the dose, respectively, with valaciclovir
      accounting for 2% and 23% of the dose, respectively. Radioactivity from an oral
      dose of [8-14C]valaciclovir (10 mg/kg) was distributed to all 14 tissues examined
      20 min postdose. The stomach, small intestine, kidney, liver, lymph nodes, and
      skin received the highest exposure to radioactivity, and the brain received the
      lowest exposure. Radioactivity in most tissues cleared by 24 hr postdose, and
      that in urine and feces accounted for essentially all of the administered dose by
      48 hr postdose. Acyclovir derived from valaciclovir (10 and 25 mg/kg) exhibited
      dose-independent pharmacokinetics. The Cmax and AUC for acyclovir achieved with
      orally administered valaciclovir were 8- and 4-fold higher, respectively, than
      those estimated for an equivalent dose of acyclovir. The half-life of acyclovir
      derived from valaciclovir was approximately 1 hr, whereas that of valaciclovir
      was approximately 7 min. Valaciclovir was more efficiently metabolized when
      administered orally, indicating first-pass intestinal and/or hepatic metabolism.
      Rapid hydrolysis of valaciclovir in rat liver and intestinal homogenates further
      suggested the significance of presystemic metabolism. These studies indicate that
      valaciclovir is an efficient acyclovir prodrug particularly suited for oral
      administration.

PMID- 8149892
TI  - Induction of cytochromes P-450 2B and 3A in mice following the dietary
      administration of the novel cognitive enhancer linopirdine.
AB  - The effects of the novel cognitive enhancer linopirdine [3,3-bis(4
      pyridinylmethyl)-1-phenylindolin-2-one] on hepatic cytochromes P-450 (CYP) and
      linopirdine metabolism were determined in female mice fed 0, 10, 50, and 250
      mg/kg/day of linopirdine in the diet for 4, 7, 14, and 28 days. Linopirdine
      induced CYP maximally by day 4 only at the highest dose, as demonstrated by
      significant (p < 0.05) increases in total spectral CYP and liver weight. SDS-PAGE
      revealed induced 52 kDa microsomal protein(s), identified as CYP2B and 3A by
      immunoblotting. Linopirdine also increased the rates of reactions selectively
      catalyzed by CYP2B and 3A (pentoxyresorufin O-dealkylation, benzphetamine N
      demethylation, erythromycin N-demethylation, and testosterone 2 beta-, 6 beta-,
      16 beta-hydroxylation), 1.7- to 3.0-fold vs. control, similar to increases
      produced by the prototypical CYP2B and 3A inducers phenobarbital and
      dexamethasone. No increase in microsomal CYP1A or 2E levels was demonstrated by
      immunoblotting or selective substrate assays. CYP induction increased the
      metabolism of linopirdine. The area under the plasma concentration-time curve of
      linopirdine after a 250 mg/kg/day dose decreased 11-fold from day 1-28, and
      microsomes from a parallel 250 mg/kg/day group metabolized linopirdine 1.9-fold
      faster than control (p < 0.05). This autoinduction was due primarily to the
      induced CYP3A, because antibodies recognizing CYP3A inhibited the microsomal
      metabolism of linopirdine by 85%, whereas antibodies to CYP2B were not
      inhibitory. In summary, the dietary consumption of 250 mg/kg/day of linopirdine
      by female mice coinduced CYP2B and 3A maximally by day 4, and resulted in an
      increased rate of metabolism of linopirdine, predominantly due to CYP3A.

PMID- 8149893
TI  - Metabolism of cyclophosphamide by lipoxygenases.
AB  - Cyclophosphamide (CP) can be cooxidized by several peroxidases. A number of
      xenobiotics also undergo cooxidation during metabolism of unsaturated fatty acids
      by lipoxygenases. The current study examined linoleic acid-dependent cooxidation
      of CP by soybean lipoxygenase and rabbit 15-lipoxygenase. Incubations of CP (0-5
      mM) with soybean lipoxygenase (0-1 x 10(4) units) and linoleic acid (0-5 mM)
      resulted in the generation of acrolein, an easily detected breakdown product of
      the initial unstable hydroxylated CP metabolite. Acrolein formation was dependent
      on time and concentrations of the enzyme, linoleic acid, and CP. The formation of
      acrolein was complete by 3 min and was favored at pHs above 7. The lipoxygenase
      inhibitors BW755C (0.1 mM), BWA4C (0.1 mM), and phenidione (0.01 mM)
      significantly inhibited the metabolism of CP to acrolein by 92, 66, and 57%,
      respectively. Vitamin E (0.1 mM), superoxide dismutase (10 units), and
      nordihydroguaiaretic acid (0.1 mM) significantly decreased acrolein generation by
      74, 76, and 77%, respectively. Glutathione (1 mM) significantly decreased
      measurable acrolein by 80%, perhaps by binding to this reactive aldehyde. One mM
      cysteine, mercaptoethane sulfonic acid, glutathione disulfide, or albumin also
      decreased measurable acrolein (16-36%), but significantly less efficiently than
      glutathione. Incubation of rabbit leukocyte 15-lipoxygenase with linoleic acid
      and CP also resulted in the generation of acrolein. These results indicate that
      lipoxygenases can cooxidize CP. The inhibitory effects of antioxidants suggest
      that this catalysis may involve free radicals.

PMID- 8149894
TI  - In vitro biotransformation of finasteride in rat hepatic microsomes. Isolation
      and characterization of metabolites.
AB  - Metabolism of finasteride ([N-(1,1-dimethylethyl)-3-oxo-4-aza-5 alpha-androst-1
      ene-17 beta- carboxamide]; MK-906), a new type of specific inhibitor of
      testosterone 5 alpha-reductase, was investigated using rat hepatic microsomes.
      The metabolism of finasteride by rat hepatic microsomes was oxygen- and NADPH
      dependent, and addition of metyrapone, 7,8-benzoflavone, and cytochrome c to the
      incubation mixture inhibited the metabolism of finasteride. It is suggested that
      the metabolic reaction of finasteride was mediated by a mixed function oxidase
      involving P-450. Four major metabolites were detected in vitro on incubating
      finasteride with hepatic microsomes of rats treated with phenobarbital (PB-Ms),
      whereas two major metabolites were found in the incubation mixture with
      microsomes of untreated rats (UT-Ms). These metabolites were isolated and
      purified by solvent extraction and semi-preparative HPLC, and identified by MS
      spectrometry and NMR spectroscopy. The metabolites consisted of omega-hydroxy
      finasteride (M-1), finasteride-omega-al (M-2), finasteride-omega-oic acid (M-3),
      and 6 alpha-OH finasteride (M-4). M-1 and M-4 are the major metabolites in UT-Ms,
      and M-1 and M-3 in PB-Ms. These studies revealed that hydroxylation of the t
      butyl group and ring hydroxylation at the 6-position were key steps in the
      metabolism of finasteride in the rat hepatic microsomes. Further, the major
      metabolite M-4 was hydroxylated at the 6 alpha-position, but not at the 6 beta
      position of the drug. This finding suggests the existence of a novel enzyme that
      catalyzes the 6 alpha-hydroxylation of the 4-azasteroid.

PMID- 8149895
TI  - Renal excretion of famotidine and role of adenosine in renal failure induced by
      bacterial lipopolysaccharide in rats.
AB  - Our previous studies have reported that bacterial lipopolysaccharide (LPS)
      dramatically changes the ability of the active tubular anion secretory system in
      rats. The present study has investigated the effects of LPS on the
      pharmacokinetics and renal handling of famotidine, an organic cation drug
      excreted primarily by an active tubular secretion mechanism in rats. The role of
      adenosine in the LPS-induced renal failure was also investigated using
      theophylline, an adenosine antagonist. Pretreatment with LPS (250 micrograms/kg)
      significantly decreased the steady-state volume of distribution, systemic
      clearance, and renal clearance (CLr) of famotidine, but not nonrenal clearance.
      No significant differences in total urinary recovery of unchanged famotidine were
      observed between treatments. Pretreatment with LPS significantly decreased the
      glomerular filtration rate (GFR), estimated as inulin clearance. LPS increased
      the clearance ratio of famotidine (CLr/GFR), but not the net tubular secretion,
      indicating that LPS has little or no effect on the active tubular cation
      secretory system. Theophylline (10 mg/kg) improved LPS-induced decrease in GFR
      without causing any changes in the pharmacokinetic parameters of famotidine.
      These findings provide further evidence that LPS produces different effects on
      the distribution and the active tubular secretory systems of anion and cation
      drugs, and that adenosine may play an important role in the induction of renal
      failure by LPS.

PMID- 8149896
TI  - Disposition of growth hormone-releasing peptide (SK&F 110679) in rat and dog
      following intravenous or subcutaneous administration.
AB  - The disposition of growth hormone releasing peptide (SK&F 110679) has been
      studied in male Sprague-Dawley rats and in male and female beagle dogs following
      intravenous (iv) and subcutaneous (sc) administration. Mass balance/excretion of
      [3H]SK&F 110679 was assessed in bile duct-exteriorized rats from which
      radiolabeled biliary and urinary excreta were quantified and characterized.
      [3H]SK&F 110679 was excreted, predominantly in the bile, and to a large extent as
      intact peptide following either iv or sc administration. Although the extent of
      biliary excretion of radiolabel was similar following iv or sc administration (60
      70% of the dose), the rate was significantly higher following iv administration.
      Using a specific plasma HPLC/fluorescence assay, the iv and sc pharmacokinetics
      of SK&F 110679 were investigated in both species. Following iv bolus
      administration, biphasic plasma concentration-time profiles were observed, and
      the initial phases were characterized by 2-4 min half-lives. Systemic plasma
      clearance was 27 ml/min/kg in the rat (0.4 mg/kg dose) and 17 ml/min/kg in the
      dog (0.5 mg/kg dose). High sc bioavailability (89-103%) was observed in both
      species; an apparent terminal half-life of 1 hr likely reflected slow absorption
      from the injection site.

PMID- 8149897
TI  - Pharmacokinetics and saturable blood-brain barrier transport of biotin bound to a
      conjugate of avidin and a monoclonal antibody to the transferrin receptor.
AB  - The delivery of biotinylated therapeutics through the blood-brain barrier (BBB)
      may be facilitated by the use of avidin-based chimeric peptide conjugates. The
      latter are formed by conjugating avidin to a BBB drug delivery vector, which is a
      protein that undergoes receptor-mediated transcytosis through the BBB. The murine
      OX26 monoclonal antibody to the rat transferrin receptor undergoes receptor
      mediated transport through the BBB, and previous studies have shown that a
      [3H]biotin/avidin-OX26 conjugate is effectively transported through the BBB.
      However, avidin is a cationic protein, which causes a marked increase in the
      systemic clearance of avidin-based conjugates from the plasma compartment. The
      present studies describe attempts to elevate the reduced plasma area under the
      curve (AUC) of [3H]biotin/avidin-OX26 by preloading or coloading with
      unconjugated OX26 antibody or unconjugated avidin. Both systemic clearance and
      BBB transport of avidin-OX26 were equally affected by OX26 preloading or
      coloading; this had inverse effects on the plasma AUC and the BBB permeability
      surface area product with no resulting change in the fractional delivery of
      [3H]biotin to brain. Conversely, avidin coloading preferentially reduced brain
      clearance of the [3H]biotin/avidin-OX26 conjugate, without substantial alteration
      in the plasma AUC and greatly reduced the fractional delivery of [3H]biotin to
      brain. In summary, these studies show that the use of avidin-based vectors
      results in rapid systemic clearance, which causes a reduction in the delivery of
      [3H]biotin to brain, despite a comparable BBB permeability coefficient for either
      the unconjugated OX26 antibody or the avidin-OX26 conjugate.

PMID- 8149898
TI  - [Examination of the ovarian activity of mares using progesterone profiles].
AB  - By means of clinical and analytical procedures (enzyme immuno assay for
      progesterone with microtiterplate method) the ovarian activity from 27 mares was
      tested over a period of several weeks. The measurement of the progesterone level
      to determine the time of ovulation was proved as suitable in the period of 1-2
      days after ovulation. In normocyclic mares (n = 17) a different development of
      the progesterone profile was detected, so that an insufficient development of the
      corpus luteum (35%) could be considered. By means of continuous measurement of
      progesterone (> or = 30 days) six of ten mares with aberrations in estrous cycle
      were considered carrying a persistent corpus luteum. Four of them showed a
      complete inactivity of the ovaries. The clinical importance of the determination
      of progesterone levels as a mean of routine diagnostic in mares with
      gynaecological problems is discussed.

PMID- 8149899
TI  - Effect of vitamin E on some leucocytic parameters and functions in transported
      calves.
AB  - The objective of this investigation was to determine the effect of vitamin E
      administration on leucocyte parameters and some of their functions in transported
      calves. In the study 8 calves, aged approx. 10 days, divided into two groups,
      were used. 20 mg of tocopheryl-acetate per kg body weight were administered
      orally to each of the 4 experimental calves 24 hours before loading. The calves
      were transported by road for 3 hours. Blood samples collected before and after
      the transportation were examined for total and differential leucocyte counts, T
      lymphocyte subpopulation, phagocytic activity, leucocyte migration, serum
      immunoglobulin levels, and for plasma vitamin E and cortisol levels. The animals
      showed a leucocytosis with neutrophilia and lymphopenia after transportation. The
      administration of vitamin E led to a decrease of cortisol level in 24 hours.
      There was no difference between groups in cortisol reaction due to transportation
      stress. Leucocyte migration has been less inhibited in the control group after
      unloading. A mild decline in phagocytic activity was observed 3 hours after
      transportation. Serum immunoglobulins were unaffected by both vitamin E
      administration and transportation. Vitamin E had no significant effect on
      leucocyte function and cortisol levels in present study.

PMID- 8149900
TI  - [The introduction of paddocks in circus elephant husbandry].
AB  - The guidelines for the keeping, the education and the using of animals in
      circuses and similar institutions, which are made in connection with the law for
      prevention of cruelty to animals, claim to keep elephants daily one hour
      unshackled in the group in a paddock. This paper deals with the effect of the
      paddock to the social, the play, and the comfort behaviour, and the stereotyped
      movements of circus elephants. Basically for the behaviour of kept elephants are
      results of observations in nature. A pilot study with 29 elephants in four
      circuses showed that the paddock enabled the elephants to carry out social and
      comfort behaviour more frequently than in the shackled keeping. The stereotyped
      movements were nearly absent by keeping the elephants in the paddock. If they
      keep shackled, this behaviour anomaly will take up much time.

PMID- 8149901
TI  - Two cases of Holstein calves with bovine leukocyte adhesion deficiency (BLAD)
      (case report).
AB  - Two Holstein calves showing clinical signs such as ulcerative stomatitis, severe
      gingivitis, periodontitis, loss of teeth and stunted growth, associated with
      marked neutrophilia, were evaluated by clinicopathologic analysis, neutrophil
      functions and flow cytometric analysis of CD18 expression on neutrophils.
      Decreased CL response, chemotaxis, yeast phagocytosis, and deficient CD18
      expression of neutrophils from affected animals were demonstrated. Pathological
      findings involved were ulcerative gingivitis, severe periodontitis, laryngitis,
      and multiple ulcers in forestomach. This study demonstrates that neutrophil
      functions are closely associated with impaired iC3b receptor, and these affected
      animals were diagnosed as bovine leukocyte adhesion deficiency (BLAD).

PMID- 8149902
TI  - Disposition kinetics of cephradine in normal and Escherichia coli infected goats.
AB  - The pharmacokinetics of cephradine was studied following single and repeated
      intramuscular injections in normal and Escherichia coli infected goats.
      Bioavailability of cephradine was determined in normal goats after a single
      intramuscular dose. The serum concentrations of cephradine following a single and
      repeated intramuscular administration of 10 mg/kg b.wt. twice daily for five
      consecutive days, peaked 2 hours after each intramuscular dose with a lower
      significant value recorded in E. coli infected goats than in normal goats. The
      absorption half-lives (t0.5(ab)) following a single intramuscular injection of
      cephradine was significantly higher in E. coli infected goats (1.18 h) than in
      normal goats (0.64 h). The elimination half-lives (t0.5(beta)) of cephradine were
      significantly higher in E. coli infected goats than in normal goats following the
      administration of fifth and ninth doses. The urine and milk concentrations of
      cephradine were significantly lower in E. coli infected goats than in normal
      goats. The mean systemic bioavailability of cephradine following a single
      intramuscular injection in normal goats was 73.9%.

PMID- 8149903
TI  - [The contributions of the hormones insulin, cortisol, somatotropin and total
      estrogen to the pathogenesis of sheep ketosis].
AB  - The concentrations of hormones, metabolites and electrolytes in plasma of 45 ewes
      have been examined repeatedly during gestation (day 80 to 149) and at the third
      day of lactation. Healthy single pregnant (n = 8) and twin pregnant ewes (n = 12)
      have been compared with ewes sick with subclinical (3-hydroxybutyrate > 1,0
      mmol/l, n = 6) and clinical (3-hydroxybutyrate > 1,6 mmol/l, n = 19) pregnancy
      ketosis. The concentration of 3-hydroxybutyrate, glucose, calcium, sodium and
      growth hormone in the plasma of the healthy animals were higher post partum than
      ante partum, while the concentrations of inorganic phosphorus, cortisol and total
      oestrogen were lower post partum than during pregnancy. In the pregnant ewes the
      concentrations of 3-hydroxybutyrate, bilirubin, total oestrogen and growth
      hormone in the plasma increased, while the concentration of insulin decreased
      with raising number of fetuses. In comparison with the healthy twin pregnant ewes
      the animals with subclinical and clinical pregnancy ketosis showed increased
      values of bilirubin, glutamate-dehydrogenase, growth hormone, total oestrogen,
      cortisol and cortisol/insulin ratios as well as decreased values of glucose,
      insulin and potassium. Individual differences of the animals within their groups
      were observed for the examined hormones as well as for glucose, calcium, sodium
      and potassium (analysis of variance). Beside multiple pregnancy low insulin
      values and high cortisol/insulin ratios, which are obviously due to individual
      disposition, influence enhanced ketogenesis and disorder of glucostasis.

PMID- 8149904
TI  - The occurrence of enzootic bovine leukosis (EBL) in Namibia--an epidemiological
      study.
AB  - A seroepidemiological survey for antibodies to bovine leukemia virus (BLV)
      (synonymous with bovine C-type and bovine leukosis virus) in cattle in Namibia
      was performed. A BLV glycoprotein antigen was used in an enzyme-linked
      immunosorbent assay (ELISA). In 410 (12.3%) out of a total of 3,343 sera, bovine
      leukemia virus antibodies were detected. The infection rate per State Veterinary
      District (SVD), varied from 0% (Keetmanshoop) to 52.6% (East-Caprivi). Since
      persistent antibodies to BLV proteins are a constant and early feature of BLV
      infection, a serological survey of cattle populations is the best method for
      detection of BLV infection.

PMID- 8149905
TI  - [The pathogenesis of subclinical laminitis in dairy cattle: studies of the hoof
      status, rumen status and blood coagulation factors].
AB  - In 50 dairy cows of the breed "Braunvieh" (36 heifers, 14 cows) of one herd the
      claw score was recorded over a period of 2 months before parturition until 6
      months after parturition. The claw scores were correlated with the clinical
      findings, the ruminal function and the blood coagulation factors calcium
      thromboplastin (TPZ), partial thromboplastin time (PTT), thrombin time (TZ) and
      antithrombin III (AT III) evaluated one day and one week after calving. The claw
      score increased from the first to the second examination, remaining on the same
      level in the postpartal period. No correlation between the claw scores and the
      ruminal function was evident. In comparison with a control group, TPZ and PTT
      were found higher one day and one week after parturition in the experimental
      group. Blood coagulation factors and claw scores were found uncorrelated.

PMID- 8149906
TI  - [The effect of different flavophospholipol levels in rabbit feed on the fattening
      rate of hybrid rabbits].
AB  - The present study was designed to evaluate the effects of dietary
      flavophospholipol ("Bambermycin") levels on the growth performance in 400 hybrid
      rabbits from weaning at 28 days until slaughter at 74 days of age. The fryers
      were randomly assigned to one of the four dietary treatments that consisted of
      either 0, 4, 8 or 16 ppm supplemental flavophospholipol. Each treatment was
      applied to 100 animals each. Dietary treatments exerted no significant effects on
      live weight, daily weight gain and feed consumption across the entire fattening
      period. However, daily weight gains in treated fryers were increased by 2.4% on
      the average. The only significant treatment effect was found in feed conversion
      (food/gain) in fryers fed 16 ppm supplementation; kilogram food intake per
      kilogram weight gain was reduced by 0.16 kg as compared to the control group.
      Mean feed conversion in treated groups was improved by 3.5% on the average. In
      addition of flavophospholipol a significantly decreased mortality was observed.
      It was remarkable, that losses caused by infection in control were exclusively
      due to infections by Bordetella species, while the treated groups were only
      caused by Pasteurella species.

PMID- 8149907
TI  - Expression of peptide YY in all four islet cell types in the developing mouse
      pancreas suggests a common peptide YY-producing progenitor.
AB  - The islets of Langerhans contain four distinct endocrine cell types producing the
      hormones glucagon, insulin, somatostatin and pancreatic polypeptide. These cell
      lineages are thought to arise from a common, multipotential progenitor cell whose
      identity has not been well established. The pancreatic and intestinal hormone,
      peptide YY, has been previously identified in glucagon-producing cells in islets;
      however, transgenic mice expressing Simian Virus 40 large T antigen under the
      control of the peptide YY gene expressed the oncoprotein in beta, delta and
      pancreatic polypeptide cells, and occasionally developed insulinomas, suggesting
      relationships between peptide YY-producing cells and several islet cell lineages.
      The four established pancreatic islet cell types were examined for coexpression
      of peptide YY in islets of normal and transgenic mice throughout development.
      Peptide YY immunoreactivity was identified in the earliest endocrine cells in the
      fetal pancreas and was coexpressed in each islet cell type during development.
      Peptide YY showed a high degree of co-localization with glucagon- and insulin
      producing cells in early pancreatic development, but by adulthood, peptide YY was
      expressed in less than half of the alpha cells and was no longer expressed in
      beta cells. Peptide YY was also coexpressed with somatostatin and pancreatic
      polypeptide when these cell types first appeared, but most delta and pancreatic
      polypeptide cells continued to express peptide YY throughout development. The use
      of conditions that distinguish peptide YY from the related peptides, pancreatic
      polypeptide and neuropeptide Y, as well as the ability of the peptide YY gene to
      direct expression of a reporter gene in islets of transgenic mice, establishes
      expression of peptide YY in the earliest pancreatic endocrine cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8149908
TI  - Cell cycles and clonal strings during formation of the zebrafish central nervous
      system.
AB  - Cell lineage analysis of central nervous system progenitors during gastrulation
      and early segmentation in the zebrafish reveals consistent coupling of specific
      morphogenetic behaviors with particular cell cycles. Cells in single clones
      divide very synchronously. Cell divisions become progressively oriented, and act
      synergistically with oriented intercalations during the interphases of zygotic
      cell cycles 15 and 16 to extend a single lineage into a long, discontinuous
      string of cells aligned with the nascent embryonic axis. Dorsalwards convergence
      brings the string to the midline and, once there, cells enter division 16. This
      division, or sometimes the next one, and the following cell movement reorient to
      separate siblings across the midline. This change converts the single string into
      a bilateral pair of strings, one forming a part of each side of the neural tube.
      The stereotyped cellular behaviors appear to account for the previously reported
      clonal restriction in cell fate and to underlie morphogenesis of a midline organ
      of proper length and bilateral shape. Regulation of cellular morphogenesis could
      be cell-cycle dependent.

PMID- 8149909
TI  - Spatially regulated expression of three receptor tyrosine kinase genes during
      gastrulation in the zebrafish.
AB  - We describe the isolation and early developmental expression of three novel
      zebrafish genes (rtk1-3) that encode members of the eph family of receptor
      tyrosine kinases. At the onset of gastrulation, rtk1 is expressed in the shield
      region corresponding to the future dorsal side of the embryo. As gastrulation
      proceeds, both rtk1 and rtk2 are expressed within the axial hypoblast along the
      entire axis of the embryo. After the gastrula stage is complete, expression of
      both genes is maintained in precursor cells of the notochord in the tail bud but
      is downregulated in other regions of the axial hypoblast, rtk3 is expressed in
      anterior axial hypoblast including the 'pillow' at the anterior tip of the
      hypoblast and in paraxial tissue in posterior regions of the embryo. We show that
      the precise spatial regulation of expression of rtk genes, ntl and goosecoid
      along the anteroposterior axis is maintained in embryos that have no dorsoventral
      axis. This indicates that the mechanisms that regulate gene expression along the
      anteroposterior and dorsoventral axes of the hypoblast may be independent.

PMID- 8149911
TI  - Cell contact regulates neuroblast formation in the Caenorhabditis elegans lateral
      epidermis.
AB  - A single line of epidermal seam cells lies along each side of the nematode C.
      elegans. During normal development, one of these cells, V5, produces a neuroblast
      that will give rise to a sensory structure, the postdeirid. If seam cells located
      either anterior or posterior to V5 are ablated however, this neuroblast formation
      is blocked. Because of this requirement for the presence of adjacent seam cells,
      we have asked whether V5's ability to produce a neuroblast depends on direct
      contact with its seam cell neighbors. We find that direct contact between seam
      cells is required for commitment to neuroblast production. Seam cells lose and
      reform their contacts with each other as they go through rounds of cell division
      during larval development. Signaling required for neuroblast formation occurs
      when the seam cells make contact after their first round of division. If this
      contact is prevented, no neuroblast is made; when it is delayed, the time of
      signaling is also delayed. The characteristics of these signals suggest that a
      seam cell must be part of a continuous epithelium in order to develop normally
      and that signaling may occur via a cell recognition/cell adhesion pathway. The
      effect of seam cell ablations on neuroblast formation is altered in mab-5(-)
      animals, suggesting that this HOM-C gene is part of the pathway by which seam
      cell signaling controls the decision to make a postdeirid neuroblast.

PMID- 8149910
TI  - bcl-2 protein expression is widespread in the developing nervous system and
      retained in the adult PNS.
AB  - Cell death is a common feature of neural development in all vertebrates. The bcl
      2 proto-oncogene has been shown to protect a variety of cell types from
      programmed cell death. We have examined the distribution of bcl-2 protein in the
      developing and adult nervous systems. bcl-2 protein is widespread during
      embryonic development. Proliferating neuroepithelial cells of ventricular zones
      as well as the postmitotic cells of the cortical plate, cerebellum, hippocampus
      and spinal cord express bcl-2. Postnatally, bcl-2 is principally retained in the
      granule cells of the cerebellum and dentate gyrus of the hippocampus. bcl-2
      expression in the CNS declines with aging. In the peripheral nervous system,
      neurons and supporting cells of sympathetic and sensory ganglia retain
      substantial bcl-2 protein throughout life. The widespread expression of bcl-2 in
      CNS and PNS neurons during embryonic development and its selective retention in
      the adult PNS is consistent with a role for bcl-2 in regulating neuronal
      survival. In addition, the expression of bcl-2 in some neuronal populations
      beyond the recognized period of cell death is suggestive of a role for bcl-2
      beyond simply protecting neurons from developmental cell death.

PMID- 8149912
TI  - Isoform-specific induction of a retinoid-responsive antigen after biolistic
      transfection of chimaeric retinoic acid/thyroid hormone receptors into a
      regenerating limb.
AB  - Retinoic acid (RA) induces secretory differentiation in the wound epidermis of a
      regenerating amphibian limb. We investigated the role of individual RA receptor
      (RAR) types in the newt wound epidermis by introducing chimaeric RA/thyroid
      hormone (T3) receptors (chi alpha 1 and chi delta 1) that can be activated by T3.
      A biolistic particle delivery system was employed to transfect cells in the wound
      epidermis of a regenerating limb and approximately 10% of the cells in targeted
      surface areas expressed marker genes. Both chi alpha 1 and chi delta 1 were
      comparable in their ability to stimulate transcription of a synthetic reporter
      construct through a RA response element after activation with T3 in situ. This
      activation was also comparable to that obtained by the endogenous complement of
      RARs in the RA-treated, transfected wound epidermis. The RA-inducible WE3
      antigen, a marker for secretory differentiation, which distinguishes the wound
      epidermis from normal skin (Tassava, R. A., Johnson-Wint, B. and Gross, J. 1986,
      J. Exp. Zool. 239, 229-240), was used to assess the functional role of chi alpha
      1 and chi delta 1. Chimaeric receptors were transfected with an alkaline
      phosphatase marker gene, activated with T3, and the expression of both the marker
      and WE3 was analyzed by double-label immunofluorescence. Newt limbs transfected
      with chi delta 1 showed many double-labelled cells dependent on the presence of
      T3, whereas contralateral limbs transfected with an alkaline phosphatase marker
      lacking chimaeric receptor sequences did not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149913
TI  - dishevelled is required during wingless signaling to establish both cell polarity
      and cell identity.
AB  - The dishevelled gene of Drosophila is required to establish coherent arrays of
      polarized cells and is also required to establish segments in the embryo. Here,
      we show that loss of dishevelled function in clones, in double heterozygotes with
      wingless mutants and in flies bearing a weak dishevelled transgene leads to
      patterning defects which phenocopy defects observed in wingless mutants alone.
      Further, polarized cells in all body segments require dishevelled function to
      establish planar cell polarity, and some wingless alleles and dishevelled;
      wingless double heterozygotes exhibit bristle polarity defects identical to those
      seen in dishevelled alone. The requirement for dishevelled in establishing
      polarity in cell autonomous. The dishevelled gene encodes a novel intracellular
      protein that shares an amino acid motif with several other proteins that are
      found associated with cell junctions. Clonal analysis of dishevelled in leg discs
      provides a unique opportunity to test the hypothesis that the wingless
      dishevelled interaction species at least one of the circumferential positional
      values predicted by the polar coordinate model. We propose that dishevelled
      encodes an intracellular protein required to respond to a wingless signal and
      that this interaction is essential for establishing both cell polarity and cell
      identity.

PMID- 8149914
TI  - Overlapping patterns of IGF2 and H19 expression during human development:
      biallelic IGF2 expression correlates with a lack of H19 expression.
AB  - The spatial patterns of IGF2 and H19 gene expression are strikingly similar
      during parts of human embryonic/fetal and early postnatal development. Notable
      exceptions were found with the ciliary anlage of the embryonic retina and the
      choroid plexus/leptomeninges, where transcripts from the IGF2 but not the H19
      locus could be detected. Moreover, in contrast to the other tissue samples
      examined, the choroid plexus/leptomeninges expressed both parental IGF2 alleles.
      Whilst RNase protection analysis revealed a weak activity of the P1 promoter in
      the choroid plexus/leptomeninges, the P2, P3 and P4 promoters were all active
      wherever IGF2 was expressed. We discuss these observations with respect to a
      hypothesized coordinated control of the reciprocally imprinted and closely linked
      IGF2 and H19 loci.

PMID- 8149915
TI  - wingless signal and Zeste-white 3 kinase trigger opposing changes in the
      intracellular distribution of Armadillo.
AB  - wingless/wnt-1 signaling directs cell fate during development. Genetic analysis
      in Drosophila identified genes that may encode components of the wingless signal
      transduction system. Drosophila Armadillo, homolog of vertebrate beta-catenin, is
      required for wingless signaling. Unlike armadillo RNA, Armadillo protein
      accumulates non-uniformly in different cells of each embryonic segment. We found
      that cells alter their intracellular distribution of Armadillo in response to
      Wingless signal, accumulating increased levels of cytoplasmic Armadillo relative
      to those of membrane-associated protein. Levels of cytoplasmic Armadillo are also
      regulated by Zeste-White 3 kinase. Analysis of double mutants demonstrates that
      Armadillo's role in wingless signaling is direct, and that Armadillo functions
      downstream of both wingless and zeste-white 3. We present a model for the role of
      Armadillo stripes in transduction of wingless signal.

PMID- 8149916
TI  - The daughterless gene functions together with Notch and Delta in the control of
      ovarian follicle development in Drosophila.
AB  - The daughterless (da) gene in Drosophila encodes a broadly expressed
      transcriptional regulator whose specific functions in the control of sex
      determination and neurogenesis have been extensively examined. We describe here a
      third major developmental role for this regulatory gene: follicle formation
      during oogenesis. A survey of da RNA and protein distribution during oogenesis
      reveals a multiphasic expression pattern that includes both germline and soma.
      Whereas the germline expression reflects da's role in progeny sex determination,
      the somatic ovary expression of da correlates with the gene's role during egg
      chamber morphogenesis. Severe, but viable, hypomorphic da mutant genotypes
      exhibit dramatic defects during oogenesis, including aberrantly defined follicles
      and loss of interfollicular stalks. The follicular defects observed in da mutant
      ovaries are qualitatively very similar to those described in Notch (N) or Delta
      (Dl) mutant ovaries. Moreover, in the ovary da- alleles exhibit dominant
      synergistic interactions with N or Dl mutations. We propose that all three of
      these genes function in the same regulatory pathway to control follicle
      formation.

PMID- 8149917
TI  - Induction of chondrogenesis: requirement for synergistic interaction of basic
      fibroblast growth factor and transforming growth factor-beta.
AB  - Interactions between the epithelial anlage of the developing mouse inner ear and
      its associated periotic mesenchyme control the differentiation of the
      cartilaginous otic capsule. Transforming growth factor-beta 1 (TGF-beta 1) is a
      naturally occurring signal peptide that is present in these tissues at times of
      active differentiation and morphogenesis. Previous studies have shown that TGF
      beta 1 alone is not a sufficient stimulus to initiate chondrogenesis in cultured
      periotic mesenchyme. In this study, we provide evidence that basic fibroblast
      growth factor (bFGF) can elicit a specific but limited chondrogenic response in
      cultured periotic mesenchymal cells. We also demonstrate that simultaneous
      addition of bFGF and TGF-beta 1 to cultured periotic mesenchyme results in a full
      chondrogenic response comparable to that which occurs when periotic mesenchyme is
      grown in the presence of its natural inductor tissue (i.e. otic epithelium).
      Utilizing antibodies directed against bFGF, we show localization of endogenous
      bFGF in the otic epithelium in vivo and in mixed epithelial-mesenchymal cultures.
      Additionally, we demonstrate the presence of FGF-like activity in medium
      conditioned by otic epithelium. Blocking of epithelial elicited chondrogenesis by
      a combination of both alpha bFGF and alpha TGF-beta 1 antibodies provides further
      evidence of the necessity for these growth factors in the chondrogenic
      differentiation of periotic mesenchyme in vitro. Our results suggest a role for
      both bFGF and TGF-beta 1 in the regulation of chondrogenesis during otic capsule
      formation in situ.

PMID- 8149918
TI  - Cell-extracellular matrix interactions under in vivo conditions during
      interstitial cell migration in Hydra vulgaris.
AB  - Interstitial cell (I-cell) migration in hydra is essential for establishment of
      the regional cell differentiation pattern in the organism. All previous in vivo
      studies have indicated that cell migration in hydra is a result of cell-cell
      interactions and chemotaxic gradients. Recently, in vitro cell adhesion studies
      indicated that isolated nematocytes could bind to substrata coated with isolated
      hydra mesoglea, fibronectin and type IV collagen. Under these conditions,
      nematocytes could be observed to migrate on some of these extracellular matrix
      components. By modifying previously described hydra grafting techniques, two
      procedures were developed to test specifically the role of extracellular matrix
      components during in vivo I-cell migration in hydra. In one approach, the
      extracellular matrix structure of the apical half of the hydra graft was
      perturbed using beta-aminopropionitrile and beta-xyloside. In the second
      approach, grafts were treated with fibronectin, RGDS synthetic peptide and
      antibody to fibronectin after grafting was performed. In both cases, I-cell
      migration from the basal half to the apical half of the grafts was quantitatively
      analyzed. Statistical analysis indicated that beta-aminopropionitrile,
      fibronectin, RGDS synthetic peptide and antibody to fibronectin all were
      inhibitory to I-cell migration as compared to their respective controls. beta
      xyloside treatment had no effect on interstitial cell migration. These results
      indicate the potential importance of cell-extracellular matrix interactions
      during in vivo I-cell migration in hydra.

PMID- 8149919
TI  - An increase in intracellular pH during neural induction in Xenopus.
AB  - In this paper, we show that an intracellular alkalinization of the dorsal
      ectoderm cells is among the earliest responses to neural induction in Xenopus.
      Planar explants of the dorsal marginal zone were prepared from embryos that had
      been microinjected during cleavage stages with the fluorescent pH indicator bis
      carboxyethyl-carboxyfluorescein-dextran (BCECF-dextran), and intracellular pH
      (pHi) was monitored continuously by emission ratio microfluorimetry. During stage
      10.5, the dorsal ectoderm cells undergo a sustained intracellular alkalinization
      of approximately 0.1 pH units in response to neural induction; in the absence of
      the inductive signal, the pH of the dorsal ectoderm cells decreases slightly.
      Ectoderm cells within planar explants of the ventral marginal zone show little
      change in pH during a similar period. This increase in intracellular pH is
      inhibited by 4, 4'-dihydrodiisothiocyanatostilbene-2, 2'-disulfonate (H2DIDS) or
      a low Na+/high Cl- medium, treatments that presumably affect anion transport.
      Under these conditions, expression of the anterior neural-specific homeobox gene
      engrailed is not detected, while the notochord-specific epitope recognized by the
      Tor-70 antibody is expressed in the presence of H2DIDS. This characteristic
      alkalinization is not evoked by pharmacological agents that reportedly alter
      ectodermal developmental pathways in Xenopus embryos, such as NH4Cl, phorbol
      esters, or cAMP-dependent protein kinase agonists. Our results suggest that an
      ionic regulatory event may participate in the regulation of gene expression in
      response to neural induction.

PMID- 8149920
TI  - Activin-mediated mesoderm induction requires FGF.
AB  - The early patterning of mesoderm in the Xenopus embryo requires signals from
      several intercellular factors, including mesoderm-inducing agents that belong to
      the fibroblast growth factor (FGF) and TGF-beta families. In animal hemisphere
      explants (animal caps), basic FGF and the TGF-beta family member activin are
      capable of converting pre-ectodermal cells to a mesodermal fate, although activin
      is much more effective at inducing dorsal and anterior mesoderm than is basic
      FGF. Using a dominant-negative form of the Xenopus type 1 FGF receptor, we show
      that an FGF signal is required for the full induction of mesoderm by activin.
      Animal caps isolated from embryos that have been injected with the truncated FGF
      receptor and cultured with activin do not extend and the induction of some genes,
      including cardiac actin and Xbra, is greatly diminished, while the induction of
      other genes, including the head organizer-specific genes gsc and Xlim-1, is less
      sensitive. These results are consistent with the phenotype of the truncated FGF
      receptor-injected embryo and imply that the activin induction of mesoderm depends
      on FGF, with some genes requiring a higher level of FGF signaling than others.

PMID- 8149921
TI  - Mesoderm induction by activin requires FGF-mediated intracellular signals.
AB  - We have examined the role of FGF signaling during activin-mediated mesoderm
      induction in Xenopus. Using dominant inhibitory mutants of FGF signal transducers
      to disrupt the FGF-signaling pathway at the plasma membrane or in the cytosol
      prevents animal cap blastomeres from expressing several mesodermal markers in
      response to exogenous activin. Dominant inhibitory mutants of the FGF receptor, c
      ras or c-raf inhibit the ability of activin to induce molecular markers of both
      dorsal and ventral mesoderm including Xbra, Mix1 and Xnot. Some transcriptional
      responses to activin such as goosecoid and Xwnt8 are inhibited less effectively
      than others, however, suggesting that there may differing requirements for an FGF
      signal in the responses of mesoderm-specific genes to activin induction. Despite
      the requirement for this signaling pathway during activin induction, downstream
      components of this pathway are not activated in response to activin, suggesting
      that activin does not signal directly through this pathway.

PMID- 8149922
TI  - The aggregation behavior of zinc-free insulin studied by small-angle neutron
      scattering.
AB  - The aggregation behavior of zinc-free insulin has been studied by small-angle
      neutron scattering as a function of pH and ionic strength of the solution. The
      pair distance distribution functions for the 12 samples have been obtained by
      indirect Fourier transformation. The results show that the diameter of the
      aggregates is 40 A at pH 11 and 10 mM NaCl, independent of the protein
      concentration. The largest diameter of about 120 A is found for pH 8, 100 mM
      NaCl, and a protein concentration of 10 mg/ml. Estimates of the pair distance
      distribution functions, free of inter-particle correlation effects, were obtained
      by an indirect Fourier transformation, omitting the data at small scattering
      vectors, which are influenced by these effects. By this procedure the weight
      averaged molecular mass and the average radius of gyration were determined. These
      parameters vary from 1.3 times the monomer mass and 14 A, to 6.8 times the
      monomer mass and 31 A, respectively. The mass distribution between the oligomers
      was determined by a model based on the crystal structure of zinc-free insulin.
      The results from this model and the Fourier transformations have been compared to
      an equilibrium model recently introduced by Kadima et al. (1993). The neutron
      scattering results agree well with the predictions of this model except that
      broader mass distributions are suggested by neutron scattering.

PMID- 8149923
TI  - A model of microtubule oscillations.
AB  - Simulations of microtubule oscillations have been obtained by a kinetic model
      including nucleation of microtubules, elongation by addition of GTP-loaded
      tubulin dimers, disassembly into oligomers, and dissolution of oligomers followed
      by nucleotide exchange at the free dimers. Dynamic instability is described by
      the on and off rates for dimer association in the growth phase, the rate of rapid
      shortening, and the transition rates for catastrophe and rescue. The latter are
      assumed to be completely determined by the current state of the system ("short
      cap hypothesis"). Microtubule oscillations and normal polymerizations measured by
      time-resolved X-ray scattering were used to test the model. The model is able to
      produce oscillations without further assumptions. However, in order to obtain
      good fits to the experimental data one requires an additional mechanism which
      prevents rapid desynchronization of the microtubules. One of several possible
      mechanisms that will be discussed is the destabilization of microtubules by the
      products of disassembly.

PMID- 8149924
TI  - Molecular dynamics simulation of a phospholipid membrane.
AB  - We present the results of molecular dynamics (MD) simulations of a phospholipid
      membrane in water, including full atomic detail. The goal of the simulations was
      twofold: first we wanted to set up a simulation system which is able to reproduce
      experimental results and can serve as a model membrane in future simulations.
      This goal being reached it is then further possible to gain insight in to those
      properties that are experimentally more difficult to access. The system studied
      is dipalmitoylphosphatidylcholine/water, consisting of 5408 atoms. Using original
      force field parameters the membrane turned out to approach a gel-like state. With
      slight changes of the parameters, the system adopted a liquid-crystalline state.
      Separate 80 ps runs were performed on both the gel and liquid-crystalline
      systems. Comparison of MD results with reliable experimental data (bilayer repeat
      distance, surface area per lipid, tail order parameters, atom distributions)
      showed that our simulations, especially the one in the liquid-crystalline phase,
      can serve as a realistic model for a phospholipid membrane. Further analysis of
      the trajectories revealed valuable information on various properties. In the
      liquid-crystalline phase, the interface turns out to be quite diffuse, with water
      molecules penetrating into the bilayer to the position of the carbonyl groups.
      The 10-90% width of the interface turns out to be 1.3 nm and the width of the
      hydrocarbon interior 3.0 nm. The headgroup dipoles are oriented at a small angle
      with respect to the bilayer plane. The resulting charge distribution is almost
      completely cancelled by the water molecules. The electron density distribution
      shows a large dip in the middle of the membrane. In this part the tails are more
      flexible. The mean life time between dihedral transitions is 20 ps. The average
      number of gauche angles per tail is 3.5. The occurrence of kinks is not a
      significant feature.

PMID- 8149925
TI  - Different thermal conditions of the extremities affect thermoregulation in
      clothed man.
AB  - The effects of different types of clothing on human deep body temperature were
      studied with six healthy male subjects in a supine posture. Two clothing
      ensembles were employed for the present study: A covered the whole body area with
      garments except the face (1.97 clo) and B covered only the trunk and the upper
      half of the extremities with garments (1.53 clo). The experiment was carried out
      in a climatic chamber at 55% +/- 5% relative humidity under cooling and warming
      temperatures: the temperature was changed from 22 degrees C to 10 degrees C
      (cooling) and returned to 22 degrees C again (warming). The major findings were:
      rectal temperature (T(re)) continued to decrease gradually in A throughout the
      experiment, whereas in B it increased during cooling, and returned to previous
      levels during warming. As a result, T(re) and chest skin temperature were
      maintained at a higher level in B than in A. Internal tissue conductances were
      greater in A than in B both during cooling and during warming. Thermal comfort
      appeared to have been influenced more by the rate of skin temperature change than
      by the level of skin temperature per se. It was concluded that peripheral
      vasoconstriction in B induced less heat flow from core to shell, and, thus, the
      core temperature was maintained at a higher level in B than in A.

PMID- 8149926
TI  - Changes in carotid blood flow and electrocardiogram in humans during and after
      walking on a treadmill.
AB  - Blood flow velocity in the common carotid artery and the electrocardiogram were
      measured simultaneously by telemetry in seven male subjects during 20-min walking
      on a treadmill at an exercise intensity corresponding to a mean oxygen uptake of
      26.0 (SD 2.9) ml.kg-1.min-1. The mean cardiac cycle was shortened from 0.814 (SD
      0.103) s to 0.452 (SD 0.054) s during this exercise. Of this shortening, 73% was
      due to shortening of the diastolic period and 27% to shortening of the systolic
      period. In the relatively small shortening of the mean systolic period [from
      0.377 (SD 0.043) s to 0.268 (SD 0.029) s], the isovolumetric contraction time was
      shortened by 56%. During exercise, the heart rate (fc) increased by 79.4% [from
      74.3 (SD 9.3) beats.min-1 to 133.3 (SD 14.8) beats.min-1], and the peak blood
      velocity (S1) in the common carotid artery increased by 56.1% [from 0.82 (SD
      0.10) m.s-1 to 1.28 (SD 0.11) m.s-1]. After exercise, the S1 decreased rapidly to
      the resting level. The fc decreased more slowly, still being higher than the
      initial resting level 5 min after exercise. The diastolic velocity wave and the
      end-diastolic foot decreased during exercise. The blood flow rate in the carotid
      artery increased transiently by 13.5% at the beginning of exercise [from 5.62 (SD
      0.63) ml.s-1 to 6.38 (SD 0.85) ml.s-1] and by 26.5% at the end of the exercise
      period [from 5.62 (SD 0.63) ml.s-1 to 7.11 (SD 1.34) ml.s-1].(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8149927
TI  - Hemodynamic and hormonal responses to lower body negative pressure in men with
      varying profiles of strength and aerobic power.
AB  - Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure
      (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness
      of reflex control of blood pressure during orthostatic challenge is associated
      with interactions between strength and aerobic power. Subjects underwent
      treadmill tests to determine peak oxygen uptake (VO2max) and isokinetic
      dynamometer tests to determine knee extensor strength. Based on predetermined
      criteria, subjects were classified into one of four fitness profiles of six
      subjects each, matched for age, height, and body mass: (a) low strength/average
      aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average
      aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of
      0.11 rad (6 degrees) head-down tilt (HDT), each subject underwent graded LBNP to 
      6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac,
      and hormonal responses were measured. All groups exhibited typical hemodynamic,
      hormonal, and fluid shift responses during LBNP, with no intergroup differences
      between high and low strength characteristics. Subjects with high aerobic power
      exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate,
      vascular peripheral resistance, and mean arterial pressure during rest, HDT, and
      LBNP. Seven subjects, distributed among the four fitness profiles, became
      presyncopal. These subjects showed greatest reduction in mean arterial pressure
      during LBNP, had greater elevations in vasopressin, and lesser increases in heart
      rate and peripheral resistance. Neither VO2max nor leg strength were associated
      with fall in arterial pressure or with syncopal episodes. We conclude that
      interactions between aerobic and strength fitness characteristics do not
      influence responses to LBNP challenge.

PMID- 8149928
TI  - Human skeletal muscle fibre types and force: velocity properties.
AB  - It has been reported that there is a relationship between power output and fibre
      type distribution in mixed muscle. The strength of this relationship is greater
      in the range of 3-8 rad.s-1 during knee extension compared to slower or faster
      angular knee extensor speeds. A mathematical model of the force: velocity
      properties of muscle with various combinations of fast- and slow-twitch fibres
      may provide insight into why specific velocities may give better predictions of
      fibre type distribution. In this paper, a mathematical model of the
      force:velocity relationship for mixed muscle is presented. This model
      demonstrates that peak power and optimal velocity should be predictive of fibre
      distribution and that the greatest fibre type discrimination in human knee
      extensor muscles should occur with measurement of power output at an angular
      velocity just greater than 7 rad.s-1. Measurements of torque:angular velocity
      relationships for knee extension on an isokinetic dynamometer and fibre type
      distribution in biopsies of vastus lateralis muscles were made on 31 subjects.
      Peak power and optimal velocity were determined in three ways: (1) direct
      measurement, (2) linear regression, and (3) fitting to the Hill equation.
      Estimation of peak power and optimal velocity using the Hill equation gave the
      best correlation with fibre type distribution (r < 0.5 for peak power or optimal
      velocity and percentage of fast-twitch fibres). The results of this study confirm
      that prediction of fibre type distribution is facilitated by measurement of peak
      power at optimal velocity and that fitting of the data to the Hill equation is a
      suitable method for evaluation of these parameters.

PMID- 8149929
TI  - Renal and cardiovascular responses to water immersion in trained runners and
      swimmers.
AB  - The purpose of this study was to determine if fluid-electrolyte, renal, hormonal,
      and cardiovascular responses during and after multi-hour water immersion were
      associated with aerobic training. Additionally, we compared these responses in
      those who trained in a hypogravic versus a 1-g environment. Seventeen men
      comprised three similarly aged groups: six long-distance runners, five
      competitive swimmers, and six untrained control subjects. Each subject underwent
      5 h of immersion in water [mean (SE)] 36.0 (0.5) degrees C to the neck.
      Immediately before and at each hour of immersion, blood and urine samples were
      collected and analyzed for sodium (Na), potassium, osmolality, and creatinine
      (Cr). Plasma antidiuretic hormone and aldosterone were also measured. Hematocrits
      were used to calculate relative changes in plasma volume (% delta Vpl). Heart
      rate response to submaximal cycle ergometer exercise (35% peak oxygen uptake) was
      measured before and after water immersion. Water immersion induced significant
      increases in urine flow, Na clearance (CNa), and a 3-5% decrease in Vpl. Urine
      flow during immersion was greater (P < 0.05) in runners [2.4 (0.4) ml.min-1]
      compared to controls [1.3 (0.1) ml.min-1]. However, % delta Vpl, CCr, CNa and
      CH2O during immersion were not different (P > 0.05) between runners, swimmers,
      and controls. After 5 h of immersion, there was an increase (P < 0.05) in
      submaximal exercise heart rate of 9 (3) and 10 (3) beats.min-1 in both runners
      and controls, respectively, but no change (P > 0.05) was observed in
      swimmers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149930
TI  - Metabolic capacity of muscle fibers from high-altitude natives.
AB  - We evaluate the effects of chronic hypoxia on the metabolic phenotype of the
      muscle fiber types of humans. The subjects were three Quechua natives residing in
      the Peruvian Andes at an altitude greater than 3300 m, and three lowlanders from
      below 700 m. Biopsy specimens were obtained from the vastus lateralis muscles of
      volunteers. Muscle fibers were identified histochemically as type 1 (oxidative),
      2a (oxidative-glycolytic) or 2b (glycolytic). The relative contribution of each
      fiber type to the total cross-sectional area of each biopsy sample was
      determined. In individual fibers, the activities of malate dehydrogenase (MDH,
      citric acid cycle), lactate dehydrogenase (LDH, glycolysis) and adenylokinase
      (high-energy phosphate) were quantified. The cross-sectional area of the muscle
      occupied by each fiber type is comparable between Quechuas and lowlanders. Type 1
      fibers are the only fiber type to demonstrate statistically significant (P < or =
      0.05) differences in enzyme activities between Quechaus and lowlanders. MDH
      activity is, on average, 19.6% less (P < or = 0.0001) and LDH activity 28.1% more
      (P < or = 0.0001) in the type 1 fibers of the Quechuas. Chronic hypoxia appears
      to produce a shift from oxidative to glycolytic metabolism in those fibers which
      are typically the most aerobic in human muscle.

PMID- 8149931
TI  - The influence of blood sampling site on lactate concentration during submaximal
      exercise at 4 mmol.l-1 lactate level.
AB  - This study examined lactate concentration during incremental and submaximal
      treadmill exercise at work rates corresponding to 4 mmol.l-1 lactate
      concentration, determined by fingertip (OBLA1) and venous blood (OBLA2).
      Initially, eight subjects performed a 4-min incremental exercise test until
      exhaustion. On two other occasions, seven of the subjects undertook submaximal
      exercise tests (30 min) at work rates corresponding to OBLA1 and OBLA2. Blood was
      simultaneously obtained from both sites at rest and at the end of each exercise
      stage during the incremental exercise, and at 5, 10, 20 and 30 min during the
      submaximal exercise and 5 min into recovery. Fingertip blood lactate
      concentrations were significantly higher (P < 0.05) than venous blood at rest,
      throughout the incremental exercise, consistently during exercise at OBLA1 and
      OBLA2, and into recovery. Data also revealed an exercise intensity-dependent
      lactate difference between the two sampling sites during both exercise protocols.
      Exercise at OBLA1 did not result in a progressive increase in lactate level nor
      exhaustion, and the lactate value at the end of 30 min corresponded to the
      predetermined value. However, exercise at OBLA2 resulted in a significantly
      higher (P < 0.05) lactate level than OBLA1, the lactate concentration at the end
      of 30 min was substantially higher than the predetermined value (P < 0.05) and
      exhaustion was evident. It is concluded that the lactate concentration value
      during incremental and submaximal exercise (at 4 mmol.l-1 OBLA) is dependent on
      the blood sampling site. This finding should be considered in studies concerned
      with the determination of OBLA.

PMID- 8149932
TI  - Renal response to head-out water immersion in Korean women divers.
AB  - Head-out water immersion (HOI) induces a profound diuresis and natriuresis, which
      may endanger the body fluid balance of breath-hold divers during prolonged diving
      work. To investigate if adaptation is acquired by professional breath-hold
      divers, we have evaluated renal responses to 3-h HOI in 5 Korean women divers
      (Amas) and 11 nondiving housewives (controls). In both control and diver groups,
      the average urine flow during 3-h immersion was four times greater and Na+
      excretion was 70%-80% greater than the pre-immersion value [urine flow: 3.7 (SD
      1.0) ml.min-1 vs 0.9 (SD 0.4), P < 0.001, in controls; 4.3 (SD 0.9) vs 1.1 (SD
      0.4), P < 0.001, in divers; Na+ excretion: 270 (SD 176) mumol.min-1 vs 161 (SD
      84), P < 0.025, in controls; 303 (SD 31) vs 164 (SD 62), P < 0.005, in divers].
      In all cases, the values for a given period were not significantly different
      between the two groups. The plasma concentrations of Na+ and osmolality, and
      renal clearance of creatinine did not change significantly. However, the osmolal
      clearance increased [from 2.0 (SD 0.8) ml.min-1 to 2.8 (SD 0.7), P < 0.05, in the
      controls; from 2.2 (SD 0.4) to 2.6 (SD 0.4), P < 0.05, in the divers] and free
      water clearance changed from negative to positive values [from -1.1 (SD 0.5)
      ml.min-1 to 1.2 (SD 0.3), P < 0.005, in the controls; from -1.2 (SD 0.4) to 1.6
      (SD 1.1), P < 0.01, in the divers] during immersion, again the pattern of change
      being similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149933
TI  - The influence of exercise/rest schedule on the physiological and psychophysical
      response to isometric shoulder-neck exercise.
AB  - Six female subjects, aged 24-34 years, performed shoulder-neck exercise for 1 h
      or until they were exhausted by holding out their arms horizontally at 60 degrees
      to the sagittal plane. One continuous and six intermittent protocols were
      applied, all with a mean load corresponding to the torque of the arms, i.e. about
      15% maximal voluntary contraction (MVC). The intermittent protocols varied
      according to cycle time (10 s, 60 s, 360 s) and duty cycle (0.33, 0.50, 0.67,
      0.83). Electromyogram (EMG), mean arterial blood pressure (BPa), heart rate (fc)
      and perceived fatigue were monitored at regular intervals during exercise. Blood
      concentrations of potassium, lactate and ammonia were determined in pre- and
      postexercise samples of venous blood. Before and up to 4 h after exercise,
      measurements were made of MVC, pressure pain threshold, proprioceptive
      performance, and of EMG, BPa and fc during 1-min arm-holding at 25% MVC.
      Endurance times ranged from about 10 min to more than 1 h, significantly relating
      to both cycle time and duty cycle. The BPa, fc, EMG amplitude and perceived
      fatigue increased early during all protocols and continued to increase throughout
      the exercise period. Duty cycle influenced all of these variables, while only BPa
      and fatigue perception were related to cycle time. Cardiovascular and
      neuromuscular recovery was incomplete for hours after several of the protocols,
      as indicated for example by a sensitized response to the 1-min arm-holding. The
      protocols differed substantially as regards the relationship between different
      responses. Thus, ranking of the protocols in terms of physiological strain was
      different, depending on the criterion variable. The result stresses the relevance
      of applying a comprehensive selection of variables when evaluating the responses
      to intermittent shoulder-neck exercise.

PMID- 8149934
TI  - The combined effects of orthostatic and mental stress on heart rate, T-wave
      amplitude, and pulse transit time.
AB  - The purpose of the present study was to determine whether cardiovascular
      reactivity to mental stress may be comparable in sitting and standing postures.
      Fifteen healthy males performed two 1-min mental arithmetic tasks, either while
      sitting or while standing, in counterbalanced order. Heart rate, pulse transit
      time, and T-wave amplitude were recorded in the last 10 s of the minute before,
      during, and after the mental arithmetic. Reactivity scores for each of the
      dependent measures were computed by calculating the percentage change from
      baseline values. Data were analyzed with multivariate and univariate repeated
      measures analysis of variance. Heart rate reactivity to the combination of
      orthostatic and mental stress was greater than to either stressor alone. Cardiac
      sympathetic reactivity was greater in response to orthostatic than to mental
      stress as revealed by greater changes in T-wave amplitude and pulse transit time
      in response to the former. No additional decreases in T-wave amplitude, in
      response to mental stress, were observed during standing, but pulse transit time
      decreased in the same situation. However, no changes in pulse transit time in
      response to mental stress were observed in the sitting position. These results
      demonstrate that cardiovascular reactivity to mental stress depends on the body
      position in which the stressor is encountered.

PMID- 8149935
TI  - Diurnal variations of serum erythropoietin in trained and untrained subjects.
AB  - The diurnal variations of serum-erythropoietin concentration ([s-EPO]) were
      investigated in six physically trained (T) and eight untrained (UT) men. The T
      subjects had a higher mean maximal oxygen uptake than UT subjects [75.7 (SEM 1.6)
      ml.min-1.kg-1 versus 48.3 (SEM 1.4) ml.min-1.kg-1, P < 0.0001] and a lower mean
      body mass index [BMI, 21.7 (SEM 0.7) kg.m-2 versus 24.4 (SEM 0.6) kg.m-2, P =
      0.02]. Each subject was followed individually for 24 h as they performed their
      normal daily activities. Venous blood samples were collected from awakening (0
      min) until the end of the 24-h period (1440 min). Both T and UT had a nadir of [s
      EPO] 120 min after awakening [10.0 (SEM 0.3) U.l-1 versus 11.5 (SEM 2.1) U.l-1, P
      > 0.05]. The UT and T increased their [s-EPO] to peak values at 960 min and 960
      1200 min, respectively (ANOVA P = 0.03) after awakening [UT: 18.4 (SEM 2.8) U.l
      1; T: 16.2 (SEM 2.5) U.l-1, P > 0.05]. The mean 24-h [s-EPO] were 14.5 (SEM 1.0)
      U.l-1 and 14.9 (SEM 0.9) U.l-1 in T and UT, respectively (P > 0.05). The
      individual mean 24-h [s-EPO] were not correlated to body mass, BMI or maximal
      oxygen uptaken. Significant diurnal variations in [s-EPO] occurred in these
      healthy subjects irrespective of their levels of physical activity.

PMID- 8149936
TI  - Metabolic cost and efficiency in two forms of squatting exercise in children and
      adults.
AB  - These experiments investigated the oxygen consumption and work efficiency of
      adults and children performing identical movement patterns. Adult men (mean age
      24) and male children (mean age 12) performed squatting exercises with and
      without a pause at the lowest point of the squat. The former were termed no
      rebound squats and the latter were termed rebound squats. Subjects performed the
      exercises without load and with loads equal to 5%, 10% and 15% of body mass. The
      results showed that the children consumed 10% more oxygen per unit total body
      mass than the adults. The gross efficiency of the adults was significantly
      greater than that of the children. Net and apparent efficiencies were not
      significantly different between the age groups. Gross and net efficiencies
      declined with load. Rebound squats required 13% less oxygen than no rebound
      squats. The gross, net and apparent efficiency of rebound squats was
      significantly greater than that of no rebound squats. It is suggested that the
      greater gross efficiencies of adults is related to their lower basal metabolic
      rate and that the greater efficiency of rebound exercise is related to the
      storage of energy in elastic tissues.

PMID- 8149937
TI  - Quantification of erector spinae muscle fatigue during prolonged, dynamic lifting
      tasks.
AB  - A method was developed to quantify erector spinae fatigue resulting from
      repetitive dynamic lifting in the sagittal plane. This method was tested with the
      data from eight male subjects lifting inertial loads of 19 kg and 17 kg during
      sessions of 20 min and 2 h, respectively. Surface EMG electrodes were applied
      over sites representing the bilateral lumbar and thoracic erector spinae and
      external oblique muscles. Maximal and submaximal isometric trunk extensor
      contractions were performed at the start, intermittently throughout, and at the
      end of the dynamic lifting trials, within an apparatus designed to control spine
      posture in the upright standing position. These exertions were used to assess the
      decreases in strength, endurance and EMG mean power frequency (fw) as well as the
      increases in EMG amplitude that have been shown to accompany muscle fatigue. The
      average of the group for extensor strength decreased 17% and 21% (P < 0.05) and
      the endurance times decreased 60% and 62% (P < 0.01) for the 2-h and the 20-min
      session, respectively. The average endurance time decreased at least 10% for each
      subject in each session. Strength decreased at least 10% in all but 2 of 16 cases
      (both in the 20-min session). The average decreases in fw were 12% (lumbar) and
      17% (thoracic; P < 0.05) in the 2-h sessions and 20% (lumbar; P < 0.05) and 14%
      (thoracic) in the 20-min sessions. There was also a significant increase in EMG
      amplitude (P < 0.05) for both muscle group in both sessions.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8149938
TI  - Influence of posture on arm exercise tolerance and physiologic responses in
      persons with spinal cord injured paraplegia.
AB  - This study compared metabolic and cardiopulmonary responses to incremental supine
      and upright sitting arm crank ergometry (ACE) in nine men with spinal cord
      injured paraplegia ranging from T1-T5. Both tests consisted of continuous graded
      ACE from rest to volitional fatigue on a modified electronically braked cycle
      ergometer with the work rate increased by 8.2 W.min-1. No significant differences
      (P > 0.05) existed for peak ACE power output (W), oxygen uptake, pulmonary
      ventilation, respiratory exchange ratio, and O2 pulse between the two tests.
      Heart rate and O2 pulse responses at six submaximal work rates representing 0-58%
      peak W were also not significantly different between postures. These data
      indicate that ACE tolerance in persons with high-lesion paraplegia was not
      enhanced when ACE was performed in the supine posture.

PMID- 8149939
TI  - Cardiac anatomy and diastolic filling in professional road cyclists.

PMID- 8149940
TI  - Effect of plasma binding of ortho- and para-I-benzoates on their distribution in
      blood and into lymph, biotransformation and excretion in rat urine.
AB  - Two positional iodine derivatives of benzoic acid, i.e. ortho- (OIB) and para-
      (PIB), were used alone and in combination with salicylic acid (SA) to study the
      effects of plasma binding on their pharmacokinetics. Their lymphatic
      bioavailability (central lymph), their biotransformation and urinary excretion in
      rats were also studied. Plasma binding of the two benzoates is different, about
      95% of PIB and approximately 50% of OIB are bound. The competitive inhibition
      effect of SA was shown by an increase in the amount of free drug in plasma in
      both benzoates. Lymphatic binding is lower compared to plasma binding, an effect
      of SA of the free faction of drug in lymph was shown only with PIB. Kinetic
      parameters of benzoates are influenced by plasma binding; significant differences
      were found mainly in total clearance and areas under concentration curves.
      Lymphatic bioavailability (FL) differs only slightly with different plasma
      binding; a significant change in FL was, however, found in PIB after SA
      premedication. Significantly higher urinary excretion of OIB as compared with PIB
      corresponds to plasma binding of drugs, SA premedication decreases total
      excretion of both benzoates. SA also changes the proportion of the individual
      fractions of metabolites of benzoates in urine.

PMID- 8149941
TI  - Influence of different doses of interferon-alpha-2b on the blood plasma levels of
      5-fluorouracil.
AB  - The blood plasma levels of 5-fluorouracil (5FU) after i.v. administration have
      been determined without and under the influence of 1, 5 or 9 million units (MU)
      preadministered interferon (IFN) in patients with gastrointestinal carcinoma. The
      co-administration of 9 MU IFN causes a doubled increase of the 5FU serum
      concentrations combined with a statistically significant change of the
      pharmacokinetics of 5FU for c0, AUC, Vd and Cltot (P < 0.005). A similar effect
      with distinctly increased serum concentrations could be observed for the
      preadministration of 5 mU IFN whereby c0 and AUC were elevated significantly (P <
      0.05), but not Vd, Cltot and cd. The preadministration of 1 MU IFN also leads to
      higher plasma levels, but no changes in the pharmacokinetics of 5FU could be
      calculated (P > 0.05). A linear correlation between the IFN dose and the
      pharmacokinetic parameters c0 (R = 0.958), AUC0-120 (R = 0.948), Vd (R = 0.941)
      and Cltot (R = 0.963) of 5FU could be found (P < 0.05), but not for the
      coefficient of distribution and t1/2el. The results indicate that the
      pharmacokinetics of 5FU might be influenced by the preadministered IFN dose.

PMID- 8149942
TI  - Comparative bioequivalence study of different brands of acetyl salicylic acid in
      human volunteers.
AB  - A double blind cross over randomized study was conducted in 7 normal healthy
      volunteers. Single dose (700 mg) of buffered aspirin or aspirin with calcium
      carbonate or aspirin with caffeine was administered orally, at least 3 days
      apart. Blood samples were drawn at different time intervals after administration
      of drug for estimation of salicylate levels. The values of different
      pharmacokinetic parameters (AUC0-infinity, Cmax and tmax) did not show any
      significant difference, suggesting that these three brands of aspirin are
      biologically equivalent.

PMID- 8149943
TI  - Non linear disposition of thiopentone following long-term infusion.
AB  - The pharmacokinetics of thiopentone administered at infusion rates ranging 4.5
      11.5 mg.kg-1.h-1 for 50-130 h was studied in 6 patients with neurologic evidence
      of severe cerebral damage. Arterial plasma concentrations of thiopentone were
      measured during and after discontinuation of the infusion. The postinfusion
      plasma concentrations were fitted to the one compartment Michaelis-Menten model.
      At the end of the infusion, the level of saturation of the enzymatic systems
      ranged 67.0-95.7%. Vm was on average 0.93 +/- 0.57 mg.l-1.h-1. The mean plasma
      clearance was 2.0 +/- 1.4 ml.min-1.kg-1. The apparent half-life of the terminal
      phase was 5.5 +/- 3.9 h.

PMID- 8149944
TI  - Effects of phenobarbital and 3-methylcholanthrene pretreatment on the
      pharmacokinetics of praziquantel in rats.
AB  - The effects of phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment on
      the pharmacokinetics of praziquantel (PZQ), a schistosomicide were studied in
      Sprague-Dawley rats. Blood samples at different time intervals were obtained by
      severing the tail vein and were analyzed for unchanged PZQ by HPLC. The PB
      pretreated rats showed a 6-fold decrease in AUC, a 5-fold decrease in Cmax and an
      8-fold increase in CLtot compared to the saline treated controls. The MC
      pretreated rats and their olive-oil treated controls did not show any
      statistically significant differences in the above parameters. These results
      suggest that PZQ is extensively metabolised by PB-inducible cytochrome P-450
      isoforms and not by MC-inducible isoforms. These findings also suggest that the
      bioavailability of praziquantel could be altered to a significant extent in
      humans taking drugs that are phenobarbital type inducers.

PMID- 8149946
TI  - Influence of fluconazole on antipyrine kinetics in rats.
AB  - The present study was undertaken to examine the effect of fluconazole on in vivo
      drug metabolism in rats, using the model substrate antipyrine. Oral doses of
      fluconazole, 20 mg/kg, were administered once (acutely) or twice daily for 4 days
      (chronically). Control animals received oral drug vehicle. Antipyrine kinetics
      were determined following an intravenous dose of 20 mg/kg given either 1 or 12 h
      after the single or last dose of fluconazole respectively. Acute fluconazole
      treatment significantly increased antipyrine half-life by 250% and reduced its
      clearance by 50%, without affecting its volume of distribution. Chronic treatment
      with fluconazole failed to affect antipyrine pharmacokinetics. This study
      demonstrates that acute fluconazole inhibits the metabolism of antipyrine in
      rats.

PMID- 8149945
TI  - Kinetics of propiverine as assessed by radioreceptor assay in poor and extensive
      metabolizers of debrisoquine.
AB  - A pharmacokinetic study with 30 mg propiverine p.o. was performed in healthy
      volunteers (10 males, 6 females, age 36-56 years, body weight 55-100 kg, body
      height 162-184 cm, Broca index 0.96-1.19). 8 of them were poor and 8 extensive
      metabolizers of the debrisoquine type hydroxylation polymorphism. The total
      anticholinergic activity of the parent compound and active metabolites was
      measured with a radioreceptor assay calibrated with the metabolite M2. The
      affinity of this metabolite to the muscarinic receptors was similar to that of
      atropine. The urinary excretion of 3 major metabolites was determined with TLC
      and densitometry. Arterial blood pressure, heart rate, diameter of pupils,
      accommodation and parotic salivary flow were also measured. The concentrations of
      anticholinergic equivalents of propiverine were below 1 ng/ml of M2. 1.4-6.0% of
      the dose were excreted as N-oxidized metabolites into the urine. The poor and
      extensive metabolizers of debrisoquine did not differ significantly with regard
      to the concentration time behaviour of the active drug components, pattern of
      major metabolites, adverse drug reactions or any pharmacodynamic parameters
      measured.

PMID- 8149947
TI  - Steady state investigation of possible pharmacokinetic interactions of moxonidine
      and glibenclamide.
AB  - The aim of the study presented here was to determine possible pharmacokinetic
      interactions of moxonidine and glibenclamide at steady state in 18 healthy male
      volunteers. Multiple oral doses of 0.2 mg of moxonidine b.i.d. (q. 12 h) and of
      2.5 mg of glibenclamide o.i.d. (q. 24 h) were administered alone and in
      combination in an open, non-randomized, three-treatment design. The preparations
      were given for 5 days in each of the 3 periods. The results of this multiple dose
      study did not indicate substantial pharmacokinetic interactions of the drugs.
      Regarding the influence of glibenclamide on the pharmacokinetics of moxonidine,
      no significant changes were seen at all. In the presence of moxonidine, a minor
      decrease of bioavailability of glibenclamide was detectable, as could be derived
      from the AUC and clearance data. The actual differences were small and not
      considered to be of clinical significance.

PMID- 8149948
TI  - Biotransformation of pethidine: a comparative study of 24 h urine in three ethnic
      groups.
AB  - 219 surgical patients of either Caucasian, Chinese or Nepalese origin were given
      pethidine 1 mg/kg by intramuscular injection as pre-operative medication. Urine
      was collected for 24 h and analysed for pethidine, pethidinic acid, pethidinic
      acid conjugates, norpethidine, norpethidinic acid, and norpethidinic acid
      conjugates. The mean proportion of the percentage of metabolites attributable to
      oxidative demethylation, hydrolysis and conjugation was almost identical in each
      ethic group (P > 0.2). It was concluded that there were no differences in the
      metabolic variability of the biotransformation of pethidine in Asians and
      Caucasians in whom the urine pH had not been acidified.

PMID- 8149949
TI  - Comparative pharmacokinetics of silipide and silymarin in rats.
AB  - The plasma level profile and the biliary excretion of silybin, the main
      flavanolignan component of silymarin, were evaluated in rats after single
      equimolar oral doses (200 mg/kg, expressed as silybin equivalents) of the silybin
      phosphatidylcholine complex silipide (laboratory code IdB 1016) and of silymarin.
      Silybin was assayed by using a specific HPLC method which allowed also the
      determination of other flavanolignans present in the biological fluids after
      administration of silymarin (i.e. silydianin, silycristin and isosilybin). After
      oral silipide, silybin reached peak plasma levels within 2 h, with a Cmax of 9.0
      +/- 3.0 micrograms/ml for unconjugated drug and 93.4 +/- 16.7 micrograms/ml for
      total (free + unconjugated drug). Maximum total biliary concentrations of silybin
      (2989 +/- 568 micrograms/ml) were observed within 2 h and the biliary recovery
      after 24 h accounted for about 13% of the administered amount. After
      administration of silymarin, unconjugated and total plasma silybin levels as well
      as biliary excretion were several-fold lower than those observed after treatment
      with silipide. Silybin recovered over a 24 h period after silymarin intake
      accounted for about 2% of the administered dose. Plasma and bile obtained after
      administration of silymarin contained also silydianin, silycristin and, to a
      greater extent, isosilybin. The concentrations of the latter compound in plasma
      and in bile were higher than those of silybin itself. The relative
      bioavailability of silipide (calculated in the target organ as the ratio between
      AUCs of cumulative biliary excretion curves) was 10-fold higher than that of
      silymarin.

PMID- 8149950
TI  - Self class I molecules protect normal cells from lysis mediated by autologous
      natural killer cells.
AB  - The surface expression of given HLA class I alleles protects target cells from
      lysis mediated by natural killer (NK) clones specific for these (or related)
      alleles. We could define two groups of NK clones specifically recognizing either
      Cw4 and related C alleles ("group 1") or Cw3 and related C alleles ("group 2"),
      respectively. Monoclonal antibodies (mAb) to class I molecules should interfere
      with the interaction between NK receptors and class I molecules, thus resulting
      in lysis of protected target cells. However, none of the numerous available mAb
      to class I molecules had this effect. Therefore, we attempted to select new mAb
      on the basis of their ability to induce lysis of Cw4- or Cw3-protected
      lymphoblastoid cell lines by "group 1" or "group 2" NK clones, respectively. From
      mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing
      either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136
      (IgM), on the basis of their ability to induce lysis of protected target cell.
      Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of
      the class I heavy chain and beta 2 microglobulin, respectively. It has been
      proposed (but not proven), that self major histocompatibility complex class I
      molecules protect normal cells from autologous NK cell lysis. Thus, we used the
      6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific ("group 1")
      and Cw3-specific ("group 2") NK clones were isolated from donors expressing the
      corresponding (or related) protective C alleles. None of these clones lysed
      autologous PHA-induced blasts, used as target cells. However, addition of the
      F(ab')2 of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells
      by "group 1" or "group 2" NK clones, respectively. These data provide direct
      evidence that the expression of class I molecules protects normal cells from
      lysis by autologous NK cells.

PMID- 8149951
TI  - Small CD4+8+TCRlow thymocytes contain precursors of mature T cells.
AB  - To evaluate directly the developmental potential of cortical CD4+8+ thymocytes,
      highly purified populations of small, nondividing CD4+8+TCRlow and large,
      dividing CD4+8+TCRhigh thymocytes from H-2d mice expressing a transgenic T cell
      receptor restricted by H-2Db (major histocompatibility complex class I) molecules
      were transferred into the thymus of normal, nonirradiated H-2b recipient mice.
      The results show that both populations generate CD4-8+ thymocytes under these
      conditions, thus providing conclusive evidence that small cortical thymocytes do
      not represent a 'dead end' but an important intermediate stage in T cell
      development.

PMID- 8149952
TI  - A second promoter and enhancer element within the immunoglobulin heavy chain
      locus.
AB  - The joining of immunoglobulin gene segments during B cell development consists of
      a tightly regulated series of rearrangement steps. A variety of experiments have
      suggested that transcription is involved in activating the locus as substrate for
      the V(D)J recombinase. Here, we have characterized a region located immediately
      upstream of the most J-proximal D element (DQ52), which contains both promoter
      and enhancer activities preferentially active in precursors of B cells.
      Interestingly, this DQ52 regulatory element is inevitably deleted in fully
      rearranged H chain genes. We propose that it is involved in the early activation
      and rearrangement events at the IgH locus.

PMID- 8149953
TI  - A directory of human germ-line V kappa segments reveals a strong bias in their
      usage.
AB  - From the genomic DNA of a single individual, we have amplified, cloned and
      sequenced 37 human germ-line V kappa segments. Four of these segments were new.
      We then compiled a comprehensive directory of all germ-line V kappa segments and
      identified 50 different sequences with open reading frames. Comparison with 236
      rearranged sequences revealed that no more than 24 of these germ-line sequences
      could be assigned rearranged counterparts, that some of these were rarely used,
      and that only about 11 sequences are used frequently. This suggests that the
      expressed V kappa repertoire is mainly derived from a limited number of segments.
      Most surprisingly, the J kappa-distal region of the locus appears to be rarely
      used: we could unambiguously assign 162 rearranged sequences to V kappa segments
      of the J kappa-proximal region, but only 5 to segments of the J kappa-distal
      region.

PMID- 8149954
TI  - Bimodal distribution of V beta 2+CD4+ T cells in human peripheral blood.
AB  - The distribution of T cells using the V beta 2 gene was studied in a group of 99
      humans. The distribution of V beta 2+CD4+ levels was bimodal. Twelve individuals
      had levels of V beta 2+CD4+ less than 2% and 86 others had values greater than
      5%. Only one individual had a value between 2% and 5%. The V beta 2 low (mean 1.3
      +/- 0.49) and V beta 2 high (mean 8.2 +/- 1.65) phenotypes were stable. The V
      beta 2 low phenotype is inherited and not limited to HLA or T cell receptor V
      beta gene complexes. The CD8V beta 2 levels of CD4V beta 2 low individuals are
      also low. The residual V beta 2+ T cells in V beta 2 low individuals were not
      anergic to V beta 2-specific stimulation. These data are compatible with the
      effects of an endogenous superantigen.

PMID- 8149956
TI  - Ca2+ mobilization in physiologically stimulated single T cells gradually
      increases with peptide concentration (analog signaling).
AB  - We have investigated Ca2+ mobilization in single T cells stimulated with their
      physiological ligand, i.e. antigenic peptide bound to major histocompatibility
      complex (MHC) molecules on antigen-presenting cells (APC). Fibroblasts expressing
      I-Ed class II molecules were pulsed with a peptide derived from the lambda 2(315)
      immunoglobulin light chain. Onto such antigen-pulsed fibroblasts were sedimented
      cloned Th1 cells loaded with Fura-2. Changes in cytosolic Ca2+ concentration in
      single T cells were continually monitored by use of an imaging system based on
      fluorometry. Ca2+ mobilization was both peptide-specific and MHC-restricted.
      Within seconds of the initial APC-T cell contact, a Ca2+ spike could be observed.
      The Ca2+ response gradually declined over a 25-min period, during which
      oscillations were noted. Various parameters characterizing the magnitude of the
      Ca2+ response (latency, increase rate, max and mean Ca2+ increase, frequency and
      period of oscillations) all correlated with the amount of peptide used for
      pulsing the fibroblasts. Thus, Ca2+ mobilization in single T cells appears not to
      be an all or none phenomenon. Rather, activation is incremental (analog
      signaling), the degree of Ca2+ mobilization probably being related to the number
      of stimulatory peptide-MHC complexes on the surface of the APC. The extent of
      calcium mobilization and lymphokine production (interleukin (IL)-2, IL-3,
      interferon-gamma) correlated, at least at the population level.

PMID- 8149955
TI  - Engagement of the CD4 receptor inhibits the interleukin-2-dependent proliferation
      of human T cells transformed by Herpesvirus saimiri.
AB  - Infection with Herpesvirus saimiri, a tumor virus of non-human primates,
      transformed human CD4+ T cell clones to permanent interleukin (IL)-2-dependent
      growth without need for restimulation with antigen and accessory cells. The IL-2
      dependent proliferation of these cells was dramatically inhibited by soluble anti
      CD4 whole antibodies, F(ab')2 and Fab fragments, and also by gp 120 of human
      immunodeficiency virus. The inhibition was not due to cell death and could be
      overcome by high concentrations of exogenous IL-2. Cell surface expression of
      CD4, and to a lesser degree the density of the IL-2 receptor alpha chain, were
      reduced upon anti-CD4 treatment. After long lasting (> 12 h) incubation with anti
      CD4, abundance and activity of CD4-bound p56lck were diminished while the free
      fraction of p56lck remained unchanged. Since IL-2 binding to its receptor
      activated only the CD4-bound fraction of p56lck, the IL-2-induced p56lck activity
      was diminished after long-term CD4 ligation. Taken together, our results suggest
      a cross talk between CD4- and IL-2 receptor-mediated signaling via p56lck.

PMID- 8149957
TI  - A novel, complement factor H-related regulatory protein expressed on the surface
      of human B cell lines.
AB  - Complement regulatory proteins present on the surface of various mammalian cells
      play an important role in controlling homologous lysis, by interacting with C3
      (and usually C4). These proteins have a similar structural motif ("short
      consensus repeat") (Reid, K.B.M., Bentley, R.D., Campbell, R.D., Chung, L.P.,
      Sim, R.B., Kristensen, T. and Tack, B.F., Immunol. Today 1986. 7:230), and the
      genes encoding them are members of the family of regulators of complement
      activation. Here we describe a hitherto unknown member of this family, a molecule
      expressed by B lymphoblastoid cells. This protein is recognized by polyclonal
      antibodies to factor H and by MAH4, a monoclonal antibody reacting with the N
      terminal portion of factor H. The cell surface protein is built up of two
      disulfide-linked chains of approximately 68 and 75 kDa. Biosynthetic labeling
      studies confirmed that it is synthesized by B cells only, but not by the
      investigated lines of other origin. When tested for its functional activity, this
      molecule was shown to act as cofactor for factor I-mediated cleavage of fluid
      phase C3b to C3bi. The protein appears to be encoded by a 3.5-kb mRNA,
      hybridizing with a cDNA probe coding for the N-terminal portion of factor H. Due
      to its cross-reactivity with anti-H antibodies, cofactor activity for factor I
      and hybridization with factor H cDNA, despite its two-chain composition, it is
      considered a factor H-like protein.

PMID- 8149958
TI  - Targeting major histocompatibility complex class II molecules to the cell surface
      by invariant chain allows antigen presentation upon recycling.
AB  - We studied the functional consequences of targeting class II molecules to either
      the cell surface or to endocytic structures by expressing HLA-DR1 in human kidney
      cells in the presence or absence of different forms of the invariant chain (Ii).
      Transfectants expressing class II molecules in the absence of Ii present
      influenza virus efficiently and co-expression of full length Ii does not further
      increase antigen presentation. Chimeric Ii containing the cytoplasmic domain of
      the transferrin receptor (Tfr-Ii) delivers class II molecules associated with Tfr
      Ii to endosomal compartments, but this does not result in efficient antigen
      presentation. When class II molecules are targeted to the cell surface by Ii
      lacking either 15 (delta 15Ii) or 23 (delta 23Ii) amino acids from the
      cytoplasmic domain, a fraction of free class II molecules is also observed.
      Whereas delta 15Ii did not affect antigen presentation by class II molecules,
      delta 23Ii inhibited, but did not abrogate, the response. We show that class II
      molecules expressed in the presence of delta 23Ii can be internalized, followed
      by degradation of delta 23Ii and return of free class II alpha beta heterodimers
      to the cell surface. A fraction of the resulting free class II molecules is
      sodium dodecyl sulfate stable, indicating that internalization and reappearance
      of class II molecules at the cell surface can be an alternative route for antigen
      presentation. In all transfectants, class II molecules were found in endocytic
      compartments that labeled for CD63 and resembled the multilaminar MIIC
      compartments found in B cell lines. Ii is not required for endosomal targeting of
      class II molecules. The number of class II molecules observed in the multilaminar
      compartments correlates with the efficiency of antigen presentation.

PMID- 8149959
TI  - Interleukin-10 inhibits the primary allogeneic T cell response to human epidermal
      Langerhans cells.
AB  - In this study, we analyzed the effect of interleukin-10 (IL-10) on the primary
      allogeneic T cell response induced by human Langerhans cells (LC), the dendritic
      cells from epidermis. We showed that IL-10 strongly inhibited the T cell
      response, provided it was added at the beginning of the mixed epidermal cell
      lymphocyte reaction (MELR). Proliferation of both CD4+ and CD8+ T cell subsets
      was affected by the cytokine. An inhibitory effect of IL-10 on human LC
      allostimulatory function was evidenced by the fact that IL-10-preincubated LC,
      but not IL-10-preincubated T cells, can display inhibitory effect. LC treatment
      with IL-10 partially inhibited the increase of HLA-DR expression on cultured LC
      as the percentage of highly positive HLA-DR cells was lower than that observed in
      the absence of the cytokine. IL-10 inhibited T cell alloreaction induced by 2-day
      cultured human LC which constitutively display high levels of HLA class II, as
      well as ICAM-1 and LFA-3 antigens. This suggests that the suppressive effect of
      the cytokine was not merely related to an impaired up-regulation of these
      molecules. Addition of IL-1 during the MELR potentiated the allogeneic T cell
      proliferation and could reverse, at least partly, the inhibitory effect of IL-10.
      Collectively, these data indicate that IL-10 can prevent the alloreaction induced
      by human dendritic cells, providing new insights into the potential clinical use
      of this cytokine.

PMID- 8149960
TI  - The progressive differentiation of primed T cells is associated with an
      increasing susceptibility to apoptosis.
AB  - Recent studies have suggested that T cell memory for recall antigens resides in
      clones of primed T cells with a short inter-mitotic half-life. In humans such
      cells express an isoform of the leukocyte common antigen termed CD45RO.
      Nevertheless, little is known of the fate of these primed T cells after initial
      activation, since no markers are available to distinguish recently primed cells
      from long-established clones. This report is focused on a spectrum of primed CD4+
      T cells characterized by an inverse relationship between the expression of two
      CD45 epitopes: CD45RB and CD45RO. We show that primed CD4+ T cells progress
      through many cycles of division from a CD45RBbrightOdull to a CD45RBdullObright
      state, resulting in a highly skewed distribution of the T cell receptor variable
      region usage within this particular population. The progressive differentiation
      defined by the shift from CD45RBbright to CD45RBdull is paralleled by the gradual
      loss of bcl-2 and gain of Fas expression, two features associated with an
      increased propensity for apoptosis. At the same time, the highly differentiated
      CD45RBdull cells selectively lose the capacity to synthesize interleukin (IL)-2,
      a cytokine which is particularly effective in preventing T cell apoptosis,
      although they produce high levels of IL-4. The inability to produce adequate
      levels of IL-2 leads to the apoptosis of primed CD45RBdull cells, when they are
      stimulated in the absence of exogenous IL-2. These observations show the crucial
      dependence of highly differentiated T cells on the availability of exogenous IL
      2, and suggest both a major constraint for the persistence of T cell memory
      maintained by continually cycling primed cells, and an important mechanism
      contributing to the maintenance of T cell homeostasis in vivo.

PMID- 8149961
TI  - B precursor acute lymphoblastic leukemia third complementarity-determining
      regions predominantly represent an unbiased recombination repertoire: leukemic
      transformation frequently occurs in fetal life.
AB  - To determine whether the ALL (acute lymphoblastic leukemia) CDR3 (third
      complementarity-determining region) repertoire represents the recombination
      repertoire, or shows evidence of selectional processes inherent to normal B cell
      differentiation or malignant transformation, we analyzed 68 ALL CDR3 regions and
      included 127 previously published sequences in the analyses. We found no evidence
      of selection prior to malignant transformation as recombination was random with
      1/3 "in frame" and 2/3 "out of frame" joinings and usage of all three D reading
      frames was observed. D and JH gene segments were predominantly unmutated which
      allowed a detailed analysis of gene usage and rearrangement characteristics. JH4
      and JH6 usage (both 32.2%) was significantly different (p = 0.005) from that
      observed in peripheral B lymphocytes. D gene family usage roughly represented D
      gene family size with the exception of the DXP and DA/K family which were over-
      and underrepresented (p = < or = 0.05), respectively. D-D fusions were found in
      26.2% of CDR3 regions. If less stringent criteria were applied DIR homology was
      found in 40/65 sequences, suggesting the frequent involvement of DIR gene
      segments in human CDR3 formation. The rearranged D genes were evenly distributed
      over the D locus, suggesting that D recombination is a predominantly random
      process, independent of physical location at the locus. Also, there was no
      correlation between JH gene usge and physical location of the rearranged D gene
      segment, which excludes a major contribution of the DJH replacement recombination
      mechanism. In 36.1% of CDR3 regions N-nucleotides at the DJH junction were
      absent. This frequency is higher than observed for peripheral B lymphocytes. It
      is suggested that for a number of ALL the initial transformational event took
      place in early fetal life. We conclude that ALL CDR3 sequences show no evidence
      of selection prior to malignant transformation, nor of extensive changes
      subsequent to malignant transformation.

PMID- 8149962
TI  - Lymphokine production induced by streptococcal pyrogenic exotoxin-A is
      selectively down-regulated by pooled human IgG.
AB  - The influence of pooled human IgG preparations for intravenous use (IVIg) on
      cytokine production induced by streptococcal pyrogenic exotoxin-A (SPE-A) was
      studied at the single-cell level using cytokine-specific monoclonal antibodies
      and indirect immunofluorescence or immunohistochemical staining. Mononuclear
      cells from healthy adult blood donors were stimulated with SPE-A alone or in the
      presence of IVIg. IVIg was added either prior to stimulation or 24 h after
      initiation of cultures, in an attempt to evaluate whether IVIg treatment could
      influence an already established systemic streptococcal disease. Cells were
      harvested after 48 or 72 h of culture and stained for the following cytokines:
      interleukin(IL)-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, IL-2, tumor necrosis
      factor interferon(IFN)-gamma and TNF-alpha and TNF-beta and granulocyte
      macrophage-colony-stimulating factor. Stimulation with SPE-A lead to extensive
      lymphokine and monokine production. With the addition of IVIg prior to
      stimulation there was a strong reduction of blast transformation and an almost
      complete inhibition of lymphokine production, in particular in the synthesis of
      IFN-gamma and TNF-beta while the synthesis of IL-1 and IL-8 was either unaffected
      or increased. Adding IVIg 24 h after SPE-A stimulation also resulted in reduced
      blast transformation and decreased synthesis of IFN-gamma and TNF-beta. These
      results indicate an immunomodulatory potential by IVIg on streptococcally induced
      T cell activation and lymphokine production.

PMID- 8149963
TI  - CD3 components at the surface of pro-T cells can mediate pre-T cell development
      in vivo.
AB  - Developmentally arrested pro-T cells (CD4-8-, IL-2R+, HSA++) of RAG-1-deficient
      mice appear to express low levels of CD3 molecules in the absence of T cell
      receptor (TcR) chains at their surface, while developmentally arrested pre-T
      cells of TcR alpha-deficient mice express low levels of a disulfide-linked TcR
      beta chain in association with CD3 molecules. Cross-linking of the CD3 modules on
      pro-T cells of RAG-1-/- mice in vivo, with either of two different CD3 epsilon
      specific monoclonal antibodies, induces differentiation of these pro-T cells into
      pre-T cells (CD4+8+, IL-2R-, HSA+), concomitant with a rapid expansion of the
      thymic T cell compartment, up to 175-fold within 12 days. The same effects can be
      produced by introduction of a mutant TcR beta transgene lacking most of the
      variable domain (delta V-TcR beta) into the RAG-1-/- background. These
      experiments suggest that cross-linking of the CD3 modules on pro-T cells mimics
      the signaling function expected of the pre-TcR complex, which is found at the
      surface of pre-T cells prior to functional TcR alpha gene rearrangement. The
      variable domain of the TcR beta chain is apparently not essential for inducing
      these aspects of T cell development.

PMID- 8149964
TI  - Isolation of tumor cell-specific single-chain Fv from immunized mice using phage
      antibody libraries and the re-construction of whole antibodies from these
      antibody fragments.
AB  - Enhanced expression of epidermal growth factor receptor (EGFR) occurs on a
      variety of malignant tissues thus making anti-EGFR antibodies possible agents for
      the diagnosis and therapy of human tumors. Standard hybridoma technology has been
      used successfully to isolate anti-EGFR antibodies from immunized mice and rats.
      This report demonstrates that phage-antibody libraries are an alternative, and
      more versatile, method for isolating antibodies from immunized mice. Anti-EGFR
      antibodies were isolated from phage-antibody libraries constructed not only from
      the spleen of an immunized mouse but also from the draining lymph node of an
      immunized mouse and from in vitro immunized mouse cells. Two of the single-chain
      Fv isolated from the phage-antibody libraries were engineered to create partially
      humanized whole antibody molecules.

PMID- 8149965
TI  - Distinct roles for CD4 and CD8 as co-receptors in T cell receptor signalling.
AB  - We demonstrate that CD4 and CD8 modify signals induced through the T cell
      receptor for antigen (TCR alpha beta) in distinct fashions. Pretreatment of CD4+
      lymph node T cells with CD4-specific monoclonal antibody results in a tenfold
      inhibition of DNA synthesis induced by anti-TCR alpha beta. In contrast,
      pretreatment of CD8+ T cells with CD8-specific mAb has no effect on DNA synthesis
      subsequently induced through TCR alpha beta. While inhibiting late activation
      signals, pretreatment with anti-CD4 does not detectably alter the pattern of anti
      TCR alpha beta-induced tyrosine phosphorylation of cellular proteins, nor
      subsequent Ca2+ mobilization. The distinct biological consequences of anti-CD4
      and anti-CD8 pretreatment correlate with the differential association of their
      respective ligands with the cellular protein tyrosine kinase, p56lck. While both
      T cell lineages contain similar levels of cellular p56lck, tenfold more is
      associated with CD4 than with CD8. This difference is associated with the
      differential effects of pretreatment with anti-CD4 and anti-CD8 on the
      distribution and activity of p56lck. Further, antibody-mediated aggregation of
      TCR alpha beta on CD4+ T cells induces the appearance of a p56lck species with
      decreased mobility in sodium dodecylsulfate-polyacrylamide gel electrophoresis.
      This effect is observed in CD4+ T cells exclusively and involves the fraction of
      p56lck which is not associated with CD4. The results presented here demonstrate
      that the signalling elements which couple the antigen receptor to second
      messenger-generating systems are under distinct physical and/or functional
      constraints in the two T cell lineages.

PMID- 8149966
TI  - Regulation of the immune response by nitric oxide differentially produced by T
      helper type 1 and T helper type 2 cells.
AB  - The balance between T helper type 1 (Th 1) and T helper type 2 (Th2) cells
      determines the outcome of many important diseases. Using cloned murine T cell
      lines, evidence is provided that Th1, but not Th2, cells can be activated by
      specific antigens or a T cell mitogen, concanavalin A, to produce large amounts
      of nitric oxide (NO). Furthermore, NO can inhibit the secretion of interleukin
      (IL)-2 and interferon-gamma by Th1 cells but has no effect on IL-4 production by
      Th2 cells. Th1 and Th2 cells can, thus, be distinguished by their differential
      production of and susceptibility to NO. NO exerts a self-regulatory effect on Th1
      cells which are implicated in immunopathology.

PMID- 8149967
TI  - A fungal metabolite which inhibits the interaction of CD4 with major
      histocompatibility complex-encoded class II molecules.
AB  - CD4, a cell-surface glycoprotein expressed on a subpopulation of T cells, is the
      receptor for class II molecules of the major histocompatibility complex (MHC II)
      and a receptor for the envelope glycoprotein (gp 120) of human immunodeficiency
      virus-1 (HIV-1). Screening of microbial metabolites for CD4-binding activity
      using an enzyme-linked immunosorbent assay based on the binding of the CD4
      specific monoclonal antibody (mAb), anti-Leu3a, identified a family of compounds
      comprising several novel polyketides. The parent compound (411F, Vinaxanthone) is
      a C28 molecule probably arising from a dimerization of two C14 polyketide units.
      It strongly inhibited the interaction of anti-Leu 3a and that of several other
      D1/D2 epitope-specific mAb with CD4, but only weakly inhibited the binding of HIV
      1 gp120. Binding of a representative MHC class II molecule, HLA-DRB*0401, was
      also inhibited by 411F with a comparable inhibitory concentration (IC50 = 1
      microM). In functional assays 411F inhibited antigen-induced CD4-dependent T cell
      proliferative responses of peripheral blood mononuclear cells. At the clonal
      level 411F exhibited selectivity in that the compound inhibited peptide-induced
      CD4+ T cell proliferative responses but not alloantigen-induced CD8+ T cell
      proliferation. It is hypothesized that 411F, a polyanionic compound in aqueous
      solution at neutral pH, inhibits CD4-dependent functions by binding over a broad
      area of the positively charged amino-terminal D1 and D2 domains implicated in the
      interaction with MHC II molecules. 411F has the potential for development as an
      immunosuppressive agent with a novel mechanism of action.

PMID- 8149968
TI  - Defective T cell receptor/CD3 complex signaling in human type I diabetes.
AB  - The autoimmune process leading to the destruction of pancreatic beta-cells is
      mediated by T lymphocytes. Peripheral T cells from subjects with preclinical and
      clinical type I diabetes respond weakly in vitro to lectin stimulation. We,
      therefore, investigated in a group of newly diagnosed diabetic patients the
      presence of a defect in the signal transduction pathway of the T cell receptor
      (TcR)/CD3 complex. Following stimulation with anti-CD3-coupled beads, the
      proliferative response in diabetic T cells was significantly decreased in
      comparison with that from normal T cells. Interestingly, addition of either
      recombinant interleukin (IL)-2 or phorbol 12-myristate 13-acetate to the cell
      culture was able to completely restore impaired anti-CD3-induced proliferation in
      diabetic T cells, suggesting the presence of a defect through the TcR/CD3
      pathway, located upstream of protein kinase C (PKC) activation and resulting in
      low IL-2 production and proliferation. Intracellular Ca2+ measurements by Fluo-3
      labeling and flow cytometry analysis on diabetic and control T cells after anti
      CD3 stimulation gave comparable results, indicating that this defect does not
      involve events leading to intracellular Ca2+ mobilization. In contrast, anti-CD3
      stimulation of diabetic T cells resulted in a marked impairment of PKC
      translocation and CD69 antigen expression, as assessed by peptide substrate
      phosphorylation and by flow cytometry analysis, respectively. Taken together, our
      data clearly show the presence in individuals at the onset of the disease of an
      in vitro defect in the signal transduction pathway of the TcR/CD3 complex,
      resulting in ineffective PKC activation which is not able to induce normal IL-2
      production and proliferation of diabetic T cells.

PMID- 8149969
TI  - Formoterol on airway smooth muscle and human lung mast cells: a comparison with
      salbutamol and salmeterol.
AB  - Formoterol, like salbutamol and salmeterol, relaxed isolated preparations of
      guinea-pig trachea and human bronchus, and inhibited antigen-induced mediator
      release from human lung fragments in a concentration-related fashion. In each
      case, these actions were mediated through beta 2-adrenoceptors, with formoterol
      being 50-120-fold more potent than salbutamol, and 2-27-fold more potent than
      salmeterol. The duration of action of formoterol was longer than that of
      salbutamol in all preparations, but was markedly shorter than that of salmeterol,
      whose actions persisted for many hours despite continuous or extensive washing of
      the tissues. In conscious guinea-pigs, inhaled formoterol, salbutamol and
      salmeterol all caused dose-related inhibition of histamine-induced
      bronchoconstriction. Formoterol was again more potent (10-20-fold) than either
      salbutamol or salmeterol. However, while the actions of a threshold-effective
      dose of formoterol persisted for less than 3 h, somewhat longer than those of
      salbutamol (< 1.5 h), an equivalent dose of salmeterol was active for at least 6
      h. Therefore, while formoterol is a potent beta 2-adrenoceptor agonist in vitro
      and in vivo, and is consistently longer-acting than salbutamol, its duration of
      action is markedly shorter than that of salmeterol.

PMID- 8149970
TI  - Effect of a bradykinin receptor antagonist, HOE 140, against bradykinin- and
      vagal stimulation-induced airway responses in the guinea-pig.
AB  - We have investigated the effect of inhaled HOE 140, a novel bradykinin B2
      receptor antagonist, against bradykinin- and vagal stimulation-induced airway
      microvascular leakage and bronchoconstriction in anesthetized guinea-pigs. Lung
      resistance was measured for 6 min after challenge, followed by measurement of
      extravasation of Evans blue dye into airway tissues, used as an index of airway
      microvascular leakage. Bradykinin was given by inhalation (1 mM, 45 breaths) and
      bilateral vagus nerves were stimulated electrically during a 5-min period (3 and
      10 Hz, 5 V, pulse width of 5 ms), both of which caused a significant increase in
      lung resistance and leakage of dye in the airway. HOE 140 (20 and 200 microM, 60
      breaths) completely abolished both the airway effects induced by bradykinin,
      whereas even the higher dose of HOE 140 had no effect against those induced by
      electrical vagal stimulation. In conclusion, airway microvascular leakage and
      bronchoconstriction induced by inhaled bradykinin are mediated by activation of
      bradykinin B2 receptors in the guinea-pig. In contrast, mechanisms via bradykinin
      B2 receptors do not play an important role in the acute airway responses induced
      by vagal stimulation.

PMID- 8149971
TI  - Effect of SR 47436, a novel angiotensin II AT1 receptor antagonist, on human
      vascular smooth muscle cells in vitro.
AB  - Proliferation of smooth muscle cells within the intima plays a key role in
      vascular occlusive disorders such as atherosclerosis and restenosis following
      balloon angioplasty. Among the factors that may be important in the development
      of vascular lesions, several authors have reported that the local angiotensin
      system participates in modulating the proliferation of smooth muscle cells after
      arterial injury. This study was therefore designed to characterize the
      antagonistic properties and to investigate the antiproliferative effect of a
      newly developed non-peptide angiotensin II AT1 receptor antagonist, SR 47436.
      This compound is a potent and competitive antagonist of the binding of
      [125I]angiotensin II to its receptor on cultured human aortic smooth muscle
      cells, exhibiting an IC50 value of 1.7 +/- 0.6 nM. SR 47436 was 10-fold more
      potent than DuP 753 (Losartan) (IC50 = 20.8 +/- 3.7 nM). In these same cells, SR
      47436 potently inhibited the angiotensin II-induced [Ca2+]i increase (IC50 = 0.53
      +/- 0.13 vs. 7.4 +/- 1.3 nM for DuP 753). Angiotensin II is a potent mitogen for
      human aortic smooth muscle cells in culture, exhibiting a maximum proliferative
      response at 1 microM. SR 47436 and Losartan prevented angiotensin II-induced
      proliferation of these cells in a dose-dependent manner (IC50 = 0.32 +/- 0.09 and
      0.71 +/- 0.08 microM, respectively). SR 47436 displayed a marked in vitro
      inhibition of serum-induced smooth muscle cell proliferation (IC50 = 5.5 +/- 0.8
      microM). A selective AT2 receptor antagonist, PD 123177 did not affect
      angiotensin II-induced responses in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8149972
TI  - Adenosine A1 receptors are not involved in contraction of canine gastric
      muscularis mucosae by adenosine analogues.
AB  - In vitro contractility studies were conducted in canine gastric muscularis
      mucosae muscle strips with the adenosine analogues 2-chloroadenosine (CIAD), 5'-N
      ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA),
      R-N6-(2-phenylisopropyl)adenosine (R-PIA), S-PIA, N6-cyclohexyladenosine (CHA)
      and (2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS21680) as well as
      the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Adenosine
      analogues contracted the muscle strips with the following rank order of potency:
      CPCA > NECA > CIAD > R-PIA > CHA > S-PIA > CGS21680. CPCA, R-PIA, and CHA were
      partial agonists. At a concentration selective for adenosine A1 receptors (50
      nM), DPCPX did not alter the concentration-response curves to CIAD or CHA.
      However, at higher concentrations (1-10 microM), DPCPX antagonized CIAD-mediated
      contractions in a competitive manner (pA2 = 6.96; slope = 0.93). CIAD-mediated
      contraction was not altered by treatment of the muscle strips with tetrodotoxin
      (1 microgram/ml) or mepyramine (1 microM). Our results indicate that adenosine A1
      receptors, nerves or mast cells are not involved in contraction of canine gastric
      muscularis mucosae by adenosine analogues.

PMID- 8149973
TI  - Involvement of the 5-HT2 receptor in the 5-HT receptor-mediated stimulation of
      prolactin release.
AB  - The present study examined the involvement of 5-HT1C and 5-HT2 receptors in the
      regulation of prolactin release in the rat. Both the mixed 5-HT2/5-HT1C receptor
      agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the
      preferential 5-HT1C agonist, 2-chloro-6-(1-piperazinyl)pyrazine monohydrochloride
      (MK-212), elicited a significant increase in plasma prolactin concentration with
      DOI about 20 times more potent than MK-212. Treatment with DOI, but not with MK
      212, induced head twitching in the rat, and this behavior was inhibited by both
      the mixed 5-HT2/5-HT1C receptor antagonist, ritanserin, and the selective 5-HT2
      receptor antagonist, amperozide. DOI-induced prolactin release was also
      antagonized by ritanserin and amperozide, whereas only ritanserin affected MK-212
      induced prolactin release. Furthermore, amperozide did not attenuate d
      fenfluramine-elicited prolactin release, which is known to be antagonized by
      ritanserin. These data suggest that the pharmacological stimulation of prolactin
      release by DOI is mediated via the 5-HT2 receptor and that the 5-HT1C receptor
      may be of importance for the physiological regulation of prolactin release.

PMID- 8149974
TI  - 31P nuclear magnetic resonance study of the effects of the calcium ion channel
      antagonist fantofarone on the rat heart.
AB  - The biochemical and mechanical effects of a new calcium ion channel antagonist,
      fantofarone ((2-isopropyl-1-((4-(3-(N-methyl-N-(3,4-dimethoxy-beta-phenethyl)
      amino) propyloxy)benzenesulfonyl))-indolizine), on isovolumic perfused rat heart
      have been assessed by using 31P nuclear magnetic resonance (NMR) spectroscopy
      together with simultaneous monitoring of myocardial mechanical function.
      Cytosolic pH and phosphocreatine, adenosine triphosphate and inorganic phosphate
      contents were monitored by using 31P NMR. Heart rate, coronary flow and left
      ventricular developed pressure were measured routinely to assess mechanical
      function. Perfusion with 10 nM, 100 nM or 1 microM fantofarone for a period of 48
      min did not cause any measurable metabolic changes. However, coronary
      vasodilatation and a partial positive inotropic effect were noted. A 15-min
      pretreatment with 100 nM did not protect against the deleterious effects of an 18
      min period of normothermic, zero-flow ischemia. In contrast, a 20-min
      pretreatment period with 1 microM fantofarone significantly improved the recovery
      of mechanical performance, metabolic activity and pH after the same 18 min of
      ischemia. While only a slight protection of the ATP pool was noted during the
      ischemic period, major beneficial effects were observed during the reperfusion
      period, such that reflow was characterized by high recoveries of left ventricular
      pressure and rate pressure product (70-80%), low end diastolic pressure (< 10 mm
      Hg), significant recovery of ATP content (to 55%), a complete repletion of the
      phosphocreatine pool and a fast return of cytosolic pH to normal value.

PMID- 8149975
TI  - Intracerebral infusion of (+)-AJ76 and (+)-UH232: effects on dopamine release and
      metabolism in vivo.
AB  - The dopamine D3- and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232
      were administered locally in the striatum and the nucleus accumbens. Their
      effects on dialysate dopamine and 3,4-di-hydroxyphenylacetic acid (DOPAC) were
      measured and compared with the effects of raclopride. (+)-AJ76 and (+)-UH232 but
      not raclopride seem to interact primarily with dopamine receptors in the terminal
      regions of the A9 and A10 dopaminergic fibers to exert their maximal effect on
      dopamine release in vivo. Thus, (+)-AJ76 and (+)-UH232 seem to recruit different
      dopamine receptor populations as compared to raclopride. Though the dopamine
      receptor antagonist-induced effects on dopamine release seem to be mediated
      mainly by dopamine receptors in the terminal areas, the effects on DOPAC by the
      different antagonists seem to be mediated mainly via effects elsewhere,
      presumably at the somatodendritic autoreceptors. Thus, it is suggested that the
      regulation of extracellular dopamine and DOPAC after treatment with dopamine
      receptor antagonists are subjected to different control mechanisms.

PMID- 8149976
TI  - Sulfate esters of hydroxy amino acids as stereospecific glutamate receptor
      agonists.
AB  - Enantiomerically pure sulfate esters of the hydroxy amino acids homoserine,
      hydroxyproline and 4-hydroxypipecolic acid were synthesized and tested on alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D
      aspartate (NMDA) receptors present in the mice cortical wedge preparation and on
      NMDA receptors present in the myenteric plexus of the guinea pig with the aim of
      finding new possible endogenous ligands (either agonists or antagonists) for
      excitatory amino acid receptors. The linear and flexible compound S-homoserine
      sulfate caused a depolarization of both AMPA and NMDA receptors. In the cortex
      its agonist action had an EC50 of 150 microM for NMDA and 300 microM for AMPA
      receptors and in the myenteric plexus its EC50 was 600 microM. The stereoisomer R
      homoserine sulfate did not depolarize the cortical wedges and failed to cause
      ileal contraction up to a concentration of 500 microM. Among the four possible
      stereoisomers of 4-hydroxyproline sulfate, which are rigid structures and may be
      regarded as cyclization forms of homoserine sulfate, t-S-hydroxyproline sulfate
      was a selective AMPA receptor agonist with an EC50 of 70 microM in the cortex.
      The other three isomers were not active as agonists up to 500 microM and none of
      them had antagonist activity. Finally, t-4-hydroxy-S-pipecolic acid-4-sulfate, a
      superior homologue of t-S-hydroxyproline sulfate, was found to be one of the most
      potent and selective NMDA receptor agonists so far described with an EC50 of 0.7
      microM in the cortex and 250 microM in the myenteric plexus.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8149977
TI  - Indirectly acting agonists. A model for the functional interaction of released
      endogenous double agonists.
AB  - A theoretical model is presented to describe the functional interaction of an
      endogenous double agonist released by an indirectly acting agonist. The model
      takes into account the functional interaction of a released double (dualistic)
      agonist and describes both functional synergism and antagonism. It was shown that
      receptor density plays an important role in determining the profiles of
      concentration-effect curves and that it is necessary that the model should
      incorporate a parameter which describes receptor density. The model predicted
      that the shape of the concentration-effect curves may be sigmoid or bell-shaped.
      The theoretical predictions are comparable with experimental results.

PMID- 8149978
TI  - Locomotor activation induced by MK-801 in the rat: postsynaptic interactions with
      dopamine receptors in the ventral striatum.
AB  - The effects of bilateral 6-hydroxydopamine-induced destruction of the dopamine
      nerve terminals in the ventral striatum (nucleus accumbens) or pharmacological
      blockade of dopamine receptors with haloperidol injected locally into this area
      were examined on the locomotor hyperactivity induced by systemic administration
      of the non-competitive NMDA receptor antagonist, MK-801 ((+)-5-methyl-10,11
      dihydro-5H-dibenzo(a,d) cyclohepten-5,10-imine hydrogen maleate salt). The
      locomotor stimulation induced by two doses of MK-801 (0.15 and 0.3 mg/kg, i.p.)
      was not attenuated by 6-hydroxydopamine bilateral lesions to the ventral
      striatum, either 7 or 14 days after the operation. The same lesion however
      reduced the locomotor activation induced by 0.5 mg/kg d-amphetamine 14 days after
      surgery. Bilateral intra-accumbens injection of haloperidol at a dose (2.5
      micrograms/side) that blocked d-amphetamine-induced hypermotility did not reduce
      the locomotor response to 0.3 mg/kg MK-801, while 5 micrograms/side haloperidol
      decreased the MK-801-induced locomotor stimulation. These results suggest that
      the locomotor response to MK-801 is dependent on an interaction between
      dopaminergic and excitatory amino acid transmission occurring postsynaptically
      rather than presynaptically in the ventral striatum.

PMID- 8149979
TI  - SB 211475, a metabolite of carvedilol, a novel antihypertensive agent, is a
      potent antioxidant.
AB  - The antioxidant effects of SB 211475, a metabolite of carvedilol, a novel
      antihypertensive agent, were studied and compared with carvedilol and other
      antioxidants such as U78517F, U74500A and probucol. SB 211475 inhibited Fe(2+)
      vitamin C-initiated lipid peroxidation, assessed as thiobarbituric acid reactive
      substance, in brain-homogenate with an IC50 of 0.28 microM. Under the same
      conditions, the IC50s of probucol, carvedilol, U74500A and U78517F were 50, 8.1,
      0.71 and 0.16 microM, respectively. SB 211475 inhibited oxidation of human low
      density lipoprotein by mouse macrophages with an IC50 of 0.043 microM. In the
      same model, the IC50s of carvedilol, U78517F and probucol were 3.8, 0.15, and
      0.80 microM, respectively. SB 211475 protected cultured bovine pulmonary artery
      endothelial cells against hydroxyl radical-initiated lipid peroxidation (IC50 =
      0.15 microM) and cell damage (lactate dehydrogenase release, IC50 = 0.16 microM),
      and promoted cell survival with an EC50 of 0.13 microM. SB 211475 also protected
      endothelial cells against xanthine/xanthine oxidase-initiated cytotoxicity and
      protected rat cerebellar neurons from hydroxyl radical-mediated cell death (EC50
      = 0.19 microM). Moreover, SB 211475 inhibited superoxide (O2-) release from human
      neutrophils stimulated by phorbol myristate acetate. These observations indicate
      that SB 211475 is a potent antioxidant and may potentially contribute to the
      therapeutic effects of carvedilol in vivo.

PMID- 8149980
TI  - Effect of chronic treatment with the antidepressant tianeptine on the hypothalamo
      pituitary-adrenal axis.
AB  - The effects of acute and chronic administration of tianeptine, a novel
      antidepressant agent, on the hypothalamo-pituitary-adrenal axis were studied in
      the adult male rat. A single injection of tianeptine did not alter the activity
      of the hypothalamo-pituitary-adrenal axis. In contrast, chronic administration of
      tianeptine (10 mg/kg twice a day for 15 days) induced a significant decrease in
      the concentration of corticotropin-releasing factor (CRF) in the hypothalamus and
      adrenocorticotropin (ACTH) in the anterior lobe of the pituitary. Chronic
      tianeptine treatment did not modify CRF levels in the cerebral cortex and
      hippocampus, and did not alter alpha-melanocyte-stimulating hormone and beta
      endorphin levels in the neurointermediate lobe of the pituitary. Using the in
      situ hybridization technique, we observed that chronic administration of
      tianeptine did not modify CRF mRNA levels in the paraventricular nucleus of the
      hypothalamus. The effect of chronic tianeptine treatment on the neuroendocrine
      response to stress was also investigated. Tube restraint stress for 30 min
      induced a significant depletion of hypothalamic CRF and a substantial increase of
      plasma ACTH and corticosterone. Tianeptine abolished the stress-induced reduction
      of hypothalamic CRF concentration and markedly reduced the stress-induced
      increase in plasma ACTH and corticosterone levels. Taken together, these results
      suggest that tianeptine acts primarily at the level of the hypothalamus: (1) in
      unstressed rats, tianeptine reduces hypothalamic CRF and pituitary ACTH contents;
      (2) in stressed animals, tianeptine attenuates the activation of the hypothalamo
      pituitary-adrenal axis.

PMID- 8149981
TI  - Phospholipase A2 inhibitors regulate the proliferation of normal uterine cells.
AB  - The effects of inhibitors of phospholipase A2, cyclooxygenase, lipoxygenase and
      cytochrome P450 activity on the proliferation of normal rat uterine stromal cells
      (UIII) were studied. At non-cytotoxic doses, inhibitors of cyclooxygenase,
      lipoxygenase and cytochrome P450 activity had no effect; UIII cells did not lose
      their ability to synthesize and secrete arachidonic acid metabolites, mainly
      prostaglandin I2 and prostaglandin E2, after successive passages. Inhibition of
      prostaglandin production did not affect their proliferation. In contrast,
      phospholipase A2 inhibitors significantly reduced UIII cell proliferation in a
      reversible and dose-dependent manner. Aristolochic acid was the most potent
      inhibitor with an IC50 of 0.3 mumol/l on day 7 of culture. Moreover, low doses of
      arachidonic acid stimulated UIII cell proliferation. Thus the proliferation of
      normal uterine stromal cells appears to be independent of arachidonic acid
      oxygenated metabolites, contrary to what is observed in tumor cells, but requires
      an intact phospholipase A2 pathway.

PMID- 8149982
TI  - Involvement of delta 1-opioid receptor antagonism in the antitussive effect of
      delta-opioid receptor antagonists.
AB  - The effects of 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid
      receptor antagonist, and naltriben, a selective delta 2-opioid receptor
      antagonist, on the capsaicin-induced cough reflex were studied in mice. I.p.
      administration of BNTX in doses from 0.1 to 3.0 mg/kg reduced the number of
      coughs dose dependently. The antitussive effect of BNTX was antagonized by [D
      Pen2,5]enkephalin (DPDPE), a selective delta 1-opioid receptor agonist, while [D
      Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, had no effect on
      the antitussive effect of BNTX. Pretreatment with nor-binaltorphimine, a
      selective kappa-opioid receptor antagonist, had no significant effect on the
      antitussive effect of BNTX. I.p. administration of naltriben, in doses of 1 and 3
      mg/kg, also significantly decreased the number of coughs. Although the
      antitussive effect of naltriben was antagonized by nor-binaltorphimine, the
      antitussive effect of naltriben was not attenuated by either DPDPE or [D
      Ala2]deltorphin II. The antitussive effects of neither BNTX nor naltriben were
      antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist.
      Thus, it seems likely that the delta 1-opioid receptor antagonism may be involved
      in the antitussive effect of delta-opioid receptor antagonists.

PMID- 8149983
TI  - Modulation by metabotropic glutamate receptor of long-term potentiation of
      population spikes in the dentate gyrus in vivo.
AB  - The effect of 2-amino-3-phosphonopropionate (AP3), a metabotropic glutamate
      receptor antagonist, on long-term potentiation (LTP) of evoked potentials in the
      dentate gyrus was investigated using anesthetized rats. Intracerebroventricular
      injection of AP3 (50 nmol) prior to application of tetanic stimulation did not
      significantly affect LTP induced by 100-pulse, 100-Hz tetanus, but inhibited the
      formation of LTP by weaker tetanus (30 pulses at 60 Hz). When AP3 was injected
      after tetanus, it did not significantly affect the established LTP. These results
      suggest that metabotropic glutamate receptors play a role in facilitation of the
      formation of LTP in the dentate gyrus in vivo.

PMID- 8149984
TI  - The effect of suramin on vasodilator responses to ATP and 2-methylthio-ATP in the
      Sprague-Dawley rat coronary vasculature.
AB  - The effect of suramin, a P2 purinoceptor antagonist, on the vasodilator response
      to adenosine 5'-triphosphate (ATP), 2-methylthio-ATP (2-meSATP) and adenosine
      were examined in the Sprague-Dawley rat coronary vasculature using the
      Langendorff heart preparation. Relaxation induced by 2-meSATP was significantly
      inhibited by suramin. Only responses to low doses of adenosine and ATP were
      inhibited by suramin. 8-(p-Sulphophenyl)theophylline (8-PSPT) did not affect the
      relaxant response to ATP and 2-meSATP at a concentration that significantly
      inhibited the response to adenosine. It is concluded that 2-meSATP acts via P2Y
      purinoceptors while ATP appears to be acting largely through a different
      mechanism. It is not acting via a P1 purinoceptor because ATP was not inhibited
      by the P1 purinoceptor antagonist 8-PSPT.

PMID- 8149985
TI  - Modification by cyclopiazonic acid and ryanodine of depolarization-induced
      constriction in rat mesenteric artery.
AB  - Cyclopiazonic acid (53 or 159 nmol/min) or ryanodine (53 or 530 nmol/min) was
      applied to perfused rat mesenteric artery contracted with 40 mM K+ and 0.1 mM
      Ca2+. Both agents transiently elevated the perfusion pressure. The transient
      pressor response to caffeine observed after ryanodine was depressed more than
      after cyclopiazonic acid. This suggests that ryanodine increased the constriction
      through acceleration of Ca2+ release while cyclopiazonic acid increased it by
      inhibiting Ca2+ uptake into Ca2+ stores. In the continued presence of ryanodine,
      the next depolarization-dependent constriction was greatly depressed, suggesting
      that Ca(2+)-induced Ca2+ release was involved in the constriction.

PMID- 8149986
TI  - Methamphetamine protects against MPTP neurotoxicity in C57BL mice.
AB  - Methamphetamine (5 mg/kg) administered 30 min prior to each injection with 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (3 x 30 mg/kg, at 24 h
      intervals) prevents the reduction of striatal levels of dopamine and its
      metabolites in C57BL mice. Methamphetamine and amphetamine inhibit the uptake of
      1-methyl-4-phenylpyridinium (MPP+) by striatal synaptosomes of rats. A 30-min
      post-treatment with methamphetamine or amphetamine also prevents the MPTP-induced
      dopamine depletion, suggesting that their protective effect is related to the
      blockade of MPP+ uptake into dopaminergic neurons. Since amphetamine and
      methamphetamine are themselves neurotoxins at higher doses, this work
      demonstrated the protection against the actions of one neurotoxin by the
      administration of another.

PMID- 8149987
TI  - 3-alpha-Chlorimperialine: an M2-selective muscarinic receptor antagonist that
      penetrates into brain.
AB  - Muscarinic M2 receptors have been found to be severely depleted in post-mortem
      brains of Alzheimer's patients. This loss of receptor may represent a useful
      diagnostic marker, if it could be quantitatively imaged with single-photon
      emission computed tomography (SPECT) or positron emission tomography (PET)
      imaging. In order to develop a radioligand with selectivity for muscarinic M2
      receptors, we now report that 3-alpha-chlorimperialine is a potent M2 receptor
      antagonist with a Ki of 0.32 nM at M2 receptors, a 12-fold selectivity for M2
      over M1 receptors, and a 5-fold selectivity for M2 over M4 receptors.
      Furthermore, 2% of the injected dose of 3-alpha-chlorimperialine per gram tissue
      penetrates into brain within 30 min, then washes out gradually. Taken together,
      these studies demonstrate that 3-alpha-chlorimperialine is a potent M2-selective
      muscarinic antagonist that penetrates into brain and may be a useful substrate
      for radioiodination and subsequent imaging of brain muscarinic M2 receptors.

PMID- 8149988
TI  - Org 2766 prevents disruption of vestibular compensation by an NMDA receptor
      antagonist.
AB  - The adrenocorticotrophic hormone fragment 4-9 (ACTH-(4-9)) analog, Org 2766 has
      been shown to accelerate vestibular compensation. However, N-methyl-D-aspartate
      (NMDA) receptor antagonists disrupt the recovery process. When Org 2766 was
      administered at a dose of 20 nmol/kg every 4 h for 52 h, it prevented the
      disruption of compensation usually produced by a single 5 mg/kg i.p. injection of
      the NMDA receptor antagonist 3-([+]-2-carboxy-piperazin-4yl)-propyl-1-phosphonic
      acid (CPP). NMDA receptor antagonists and ACTH-like peptides may produce their
      effects on compensation by acting directly or indirectly at the same receptor
      complex.

PMID- 8149989
TI  - Evidence that a serotonergic mechanism is involved in the anticonvulsant effect
      of fluoxetine in genetically epilepsy-prone rats.
AB  - Fluoxetine (15 mg/kg i.p.) decreased the audiogenic seizure intensity in 33% of
      severe seizure genetically epilepsy-prone rats (GEPR-9s). 5-Hydroxytryptophan (5
      HTP, 12.5 mg/kg i.p.) produced no anticonvulsant effect in GEPR-9s. When GEPR-9s
      were treated with a combination of these two drugs, the combination treatment
      decreased the audiogenic seizure intensity in 83% of the animals tested. Brain
      microdialysis studies showed that the same combination of 5-HTP and fluoxetine
      also produced a marked potentiation of the increase in the extracellular
      serotonin concentration in the thalamus of freely-moving GEPR-9s when compared
      with administration of either drug alone. A negative correlation between
      audiogenic seizure intensity and extracellular serotonin concentration existed
      after either fluoxetine alone or the combination treatment. No significant
      changes in extracellular norepinephrine concentrations were observed after the
      combination treatment. These results coupled with our earlier reports strongly
      suggest that a serotonergic mechanism is involved in the anticonvulsant effects
      of fluoxetine in GEPRs.

PMID- 8149990
TI  - Potentiation of MK-801-induced breathing impairment by 2,3-dihydroxy-6-nitro-7
      sulfamoyl-benzo(F)quinoxaline.
AB  - The purpose of our study was to examine whether a significant interaction occurs
      between NMDA and non-NMDA receptor antagonists on respiratory function. For this
      purpose chloralose-anesthetized cats were used and respiratory minute volume
      (VE), tidal volume (Vt) respiratory rate (f), inspiratory and expiratory
      durations, and end tidal CO2 (FeCO2) were monitored. In some animals, phrenic
      nerve activity was also continuously recorded. In five spontaneously breathing
      animals, the NMDA receptor antagonist MK-801 was administered in a dose of 0.1
      mg/kg i.v., and produced decreases in VE, Vt, f and increases in inspiratory
      duration and FeCO2. Using these five animals exhibiting respiratory effects from
      prior MK-801 dosing, we then administered the non-NMDA receptor antagonist NBQX
      (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) i.v. in a dose of 3
      mg/kg. This dose is too low to produce a neuroprotective effect in animal models
      of brain ischemia. In each of the five animals NBQX administration produced an
      immediate impairment of respiration, culminating in apneusis within 55 s after
      i.v. injection. In terms of phrenic nerve discharge, inspiratory duration was
      increased approximately 4-fold by MK-801, and with the addition of NBQX,
      continuous discharge of the phrenic nerve occurred. Finally, NBQX given i.v. to
      animals not pretreated with MK-801 had only a slight depressant effect on
      respiratory activity. These results obtained with co-administration of low doses
      of two drugs that block NMDA and non-NMDA receptors raise the spector that
      combined use of these agents to ameliorate disorders in neurological function may
      be extremely deleterious to respiratory function.

PMID- 8149991
TI  - The decompensatory phase of acute hypovolaemia in rabbits involves a central
      delta 1-opioid receptor.
AB  - Graded caval occlusion in conscious rabbits caused a biphasic response. Phase I
      was characterized by a fall in conductance so that arterial pressure was
      maintained. When cardiac output had fallen to 69 +/- 2% of its baseline level,
      phase II supervened. During phase II, conductance rose abruptly and arterial
      pressure fell to a life-threatening level (< 40 mmHg). Centrally administered
      delta-opioid receptor antagonists prevented the occurrence of phase II. The
      relative order of potency was 7-benzylidene-naltrexone (BNTX, delta 1-selective)
      > N,N-diallyl-Tyr-Aib-Phe-Leu-OH (ICI 174,864) > naltrindole (delta 2-selective).
      It is concluded that a central delta 1-opioid receptor is involved in the onset
      of the second decompensatory phase of the haemodynamic response to haemorrhage.

PMID- 8149992
TI  - Inhibition by SKF 525A and quinacrine of endogenous glibenclamide-sensitive K+
      channels in follicle-enclosed Xenopus oocytes.
AB  - Effects of local anesthetics-related drugs, SKF 525A (proadifen, a cytochrome
      P450 inhibitor) and quinacrine (a phospholipase A2 inhibitor) on glibenclamide
      sensitive K+ currents were investigated using native Xenopus oocytes. SKF 525A
      and quinacrine suppressed cromakalim-induced/glibenclamide-sensitive K+ currents
      with IC50 values of 9.8 microM and 4.4 microM, respectively. Inhibitors of either
      cytochrome P450 or phospholipase A2, which are structurally unrelated to local
      anesthetics, however, did not affect the K+ currents. Similar results were
      obtained for Y-26763-induced/glibenclamide-sensitive K+ currents. SKF 525A and
      quinacrine block the glibenclamide-sensitive K+ currents by a mechanism
      irrelevant to the inhibition of cytochrome P450 or phospholipase A2 in oocytes.

PMID- 8149993
TI  - Myocardial infarction and purine transport inhibition in anaesthetised ferrets.
AB  - The potential cytoprotective effect of the purine transport inhibitor S-(p
      nitrobenzyl)-6-thioinosine (NBTI) in a model of myocardial ischaemia and
      reperfusion was investigated in the anaesthetised ferret. The left anterior
      descending coronary artery (LAD) was occluded for 90 min, producing ischaemia in
      53 +/- 3% of the left ventricular free wall, followed by 240 min reperfusion.
      NBTI (0.5 mg kg-1, i.v.) was given prior to ischaemia or prior to reperfusion. In
      addition the effect of purine transport inhibition was investigated in animals
      subjected to ischaemia without reperfusion. NBTI reduced infarct size from 84.0
      +/- 1.7 to 71.4 +/- 3.7% of the area at risk (P < 0.05) when given prior to
      occlusion of the LAD. NBTI was ineffective however when given 15 min prior to
      reperfusion. NBTI had no effect upon infarct size produced by ischaemia without
      reperfusion. The effect of NBTI was independent of significant changes in
      myocardial blood flow during ischaemia and reperfusion or upon neutrophil
      infiltration.

PMID- 8149994
TI  - The effects of MK-801 on body temperature and behavior in the rat: cross
      sensitization and cross-tolerance with phencyclidine.
AB  - The purpose of the present study was to compare the acute and repeated
      administration of MK-801 (dizocilpine) on body temperature and behavior in the
      rat, and to determine whether there is cross-tolerance and/or cross-sensitization
      to phencyclidine (PCP) after repeated administration of MK-801. The acute
      administration of MK-801 increased body temperature, and this response was
      enhanced after repeated drug administration. PCP had little effect on body
      temperature in control rats, but produced increases in body temperature in rats
      treated daily with MK-801. The acute administration of MK-801 produced ataxia,
      locomotion, sniffing, and head-weaving, and after repeated drug administration
      both ataxia and head-weaving were reduced. PCP-induced ataxia, backpedalling,
      head-weaving, and turning behaviors were decreased in rats treated daily with MK
      801, but PCP-induced locomotion and rearing were increased. These results
      indicate that there is cross-sensitization to the hyperthermic and locomotor
      effects of MK-801 and PCP, but there is cross-tolerance to some of the other
      behavioral effects of the drugs.

PMID- 8149995
TI  - Harman (1-methyl-beta-carboline) is a natural inhibitor of monoamine oxidase type
      A in rats.
AB  - Harman (1-methyl-beta-carboline) displaces [3H]pargyline in vitro from high
      affinity binding sites on membranes from cerebral cortex, provided that
      experimental conditions are chosen under which [3H]pargyline labels selectively
      monoamine oxidase type A. Norharman (beta-carboline) is a much weaker displacing
      compound. It is well known that the type A enzyme can be blocked irreversibly in
      vivo by treatment of rats with clorgyline. Under these conditions no specific
      binding of [3H]harman and [3H]pargyline to monoamine oxidase type A was detected
      in brain, whereas the specific binding was reduced to 5% in liver tissue. The in
      vitro and ex vivo experiments suggest that there is a specific binding site for
      harman on monoamine oxidase type A, thereby extending earlier in vitro findings.
      It has been postulated that harman operates as a natural inhibitor of monoamine
      oxidase type A in mammals. The present study demonstrates that harman and
      norharman occur in rat brain, blood plasma, heart, kidney and liver. It further
      shows that pretreatment with clorgyline induces a time-dependent increase in the
      blood plasma levels of harman, suggesting the displacement of harman from the
      enzyme in tissue with its subsequent delivery into the blood. These findings
      strongly support the hypothesis based on in vitro experiments, that harman binds
      reversibly to the active site of monoamine oxidase type A in vivo. Dietary
      sources for mammalian harman play probably only a minor role, because the
      concentrations in beer and wine as well as other foodstuffs are too low to
      contribute substantially to endogenous levels of harman.

PMID- 8149996
TI  - Mesolimbic sites mediate the discriminative stimulus effects of morphine.
AB  - The neuroanatomical basis of opiate addiction has been studied using a variety of
      behavioural techniques. Mesolimbic structures such as the ventral tegmental area
      and nucleus accumbens appear to be critical in mediating the expression of
      rewarding effects of opiates. However, the role of these brain structures in
      mediating the discriminative stimulus effects have not been fully examined. The
      aim of the present study was to investigate the role of the ventral tegmental
      area and the nucleus accumbens in a two-lever operant drug discrimination
      paradigm. Male Wistar rats were trained to discriminate morphine (3.0 mg/kg s.c.)
      from saline with a fixed ratio schedule of food reinforcement (FR10). Once rats
      had acquired the discrimination, a randomised sequence of morphine
      microinjections (1-10 micrograms) were evaluated. Subsequently, tests with
      morphine (1.0-10.0 mg/kg s.c.) administered systemically were performed to
      confirm the integrity of the discrimination. Small doses of morphine (1-3
      micrograms) administered into the ventral tegmental area proved sufficient to
      produce generalisation to the systemic cue, whereas similar injections into the
      nucleus accumbens produced only partial generalisation. Furthermore, these intra
      nucleus accumbens injections (3-10 micrograms) produced significant increases in
      the latency to complete the first ratio. Similar doses of morphine administered
      into the striatum failed to show generalisation. These results demonstrate that
      activation of opioid receptors located within mesolimbic structures mediate, in
      part, the discriminative stimulus effects of morphine. Furthermore, the finding
      that the discriminative stimulus effects and rewarding effects share common
      neural pathways suggest a possible linkage between the two stimulus properties.

PMID- 8149997
TI  - Influence of ifenprodil on the ACTH-induced behavioral syndrome in rats.
AB  - Ifenprodil--an antagonist at the modulatory site of the NMDA receptor complex
      sensitive to polyamines--intraperitoneally injected at doses of 3 or 10 mg/kg,
      dose dependently prevented the behavioral syndrome induced by
      intracerebroventricular administration of adrenocorticotropin (ACTH)-(1-24) in
      adult male rats (excessive grooming, stretching, yawning, penile erections).
      These data further support a role of the brain ornithine decarboxylase (ODC)
      polyamine system in the ACTH-induced behavioral syndrome, and may suggest an
      involvement of excitatory amino acids.

PMID- 8149998
TI  - An outbreak of diarrhoeal disease attributed to Shigella sonnei.
AB  - An outbreak of gastroenteritis occurred in a village on the Island of Crete, with
      1479 inhabitants. One hundred and thirty-eight symptomatic patients from 57
      different families were examined. Thirty percent of children under 12 years were
      affected compared with 4% of adolescents and adults (P < 0.0001). Thirty-five out
      of 105 stool cultures (33%) grew Shigella sonnei. Thirty-four isolates had the
      same susceptibility pattern and were sensitive to ampicillin, while one was
      resistant to this antibiotic. Thirty-three isolates had the same plasmid profile.
      Based on epidemiologic and environmental findings, it was concluded that the
      transmission of shigellosis was waterborne. Shigella were not isolated from
      water, but one of the three village springs was found to be contaminated with
      faecal coliforms. This spring was probably contaminated by sewage material, due
      to its proximity to a source of untreated sewage effluent. Implementation of
      environmental and control measures brought the epidemic to an end.

PMID- 8149999
TI  - In vivo R-plasmid transfer in a patient with a mixed infection of shigella
      dysentery.
AB  - Transfer of shigella R-plasmids in vivo has seldom been demonstrated. Strains of
      Shigella dysenteriae type 1 and Shigella flexneri type 5b were isolated from a
      Bulgarian traveller who visited Vietnam and developed dysentery, which was
      treated with trimethoprim/sulfamethoxazole (TMP/SMZ) for a short time. Both
      species of shigellae are unusual in Bulgaria where strains of S. sonnei
      predominate. Both shigella strains were multiresistant to the same antimicrobial
      agents. Each strain contained a 48-kilobase plasmid that conferred the entire
      resistance phenotype to a susceptible Escherichia coli. Restriction endonuclease
      patterns of plasmid DNA from the respective strains were identical. Transmissible
      plasmids of the same resistance phenotypes and restriction patterns were isolated
      from the patient's colonic E. coli. Transconjugants hybridized to a dihydrofolate
      reductase type I-DNA probe. These studies support the hypothesis that R-plasmid
      transfer may occur between non-pathogenic, faecal strains and pathogenic
      shigellae, a process that may have been facilitated by inadequate treatment with
      TMP/SMZ at the onset of the illness.

PMID- 8150000
TI  - Insertion sequence IS200 fingerprinting of Salmonella typhi: an assessment of
      epidemiological applicability.
AB  - When Pst I-generated digests of genomic DNA from each of the type strains of 49
      of the Vi phage types of Salmonella typhi were probed with a PCR-amplified IS200
      gene probe, all strains were found to possess at least 11 IS200 elements carried
      on fragments in the range 24.2-1.2 kb. Fourteen fingerprints were identified but
      two patterns designated IS200Sty1 and IS200Sty2 predominated. In one strain, a
      plasmid-mediated IS200 element was identified. When IS200 fingerprinting was
      applied to epidemiologically-unrelated strains of S. typhi isolated in Ecuador, 3
      patterns were identified in 10 strains belonging to 9 different phage types. It
      is concluded that Vi phage typing remains the method of choice for the primary
      differentiation of S. typhi but that IS200 fingerprinting may be of limited use
      in laboratories which do not have access to phage typing.

PMID- 8150001
TI  - Bacterial flora of Tasmanian SIDS infants with special reference to pathogenic
      strains of Escherichia coli.
AB  - The general bacterial flora of 38 Tasmanian SIDS infants was examined together
      with faecal flora of 134 comparison infants ranging in age from birth to 6
      months. The microflora of all specimens received was investigated with special
      emphasis on the toxigenic Escherichia coli (TEC). Samples were examined for
      verocytotoxigenic E. coli, free faecal verocytotoxin (FVT), heat labile toxin
      (LT) and heat stable toxin (ST) producers with the use of a Vero cell assay and
      commercial kits. The findings of this study revealed a high isolation rate (39%)
      of TEC from SIDS infants as compared to 1.5% from the healthy comparison infants.
      Atypical E. coli strains were also identified during the study, including E. coli
      A-D. An analysis of the same specimens for rotaviral and adenoviral antigens
      indicated that 30% of the SIDS cases were positive as compared to 20% in the
      comparison group.

PMID- 8150002
TI  - Seasonal variations in the occurrence of Vibrio vulnificus along the Dutch coast.
AB  - The seasonal variation in the occurrence of V. vulnificus in relation to water
      temperature and salinity was studied along the Dutch coast. In two consecutive
      years V. vulnificus strains could be isolated in August when the water
      temperature was highest. The indole-positive strains isolated from North Sea
      water samples were identical to most strains isolated from human disease and from
      the environment. However, strains isolated from four of five patients living in
      countries around the North Sea were different from the North Sea isolates in that
      they were indole-negative and have a lower NaCl tolerance.

PMID- 8150003
TI  - Characterisation of haemolytic activity from Aeromonas caviae.
AB  - Aeromonas caviae, an enteropathogen associated with gastroenteritis, displays
      several virulence characteristics. Studies on the kinetics of growth of A. caviae
      and expression of beta-haemolytic toxin revealed that A. caviae produced maximum
      haemolytic activity extracellularly during the stationary phase. Preliminary
      studies on the properties of A. caviae haemolysin suggested that divalent cations
      (Mg2+ and Ca2+) and thiol compounds, dithiothreitol and mercaptoethanol enhanced
      the haemolytic activity. Addition of L-cysteine, glutathione and EDTA reduced the
      haemolytic activity. The iron chelator, 2-2' bipyridyl, significantly inhibited
      the growth of A. caviae possibly by iron limitation, with parallel enhancement of
      haemolysin production compared to A. caviae grown in excess of iron. These
      results suggest that A. caviae produces only beta-haemolysin, which resembles the
      haemolysins reported for several other bacteria and the activity might be
      regulated by environmental factors especially iron.

PMID- 8150004
TI  - An additional set of phages to characterize epidemic methicillin-resistant
      Staphylococcus aureus strains from Spain (1989-92).
AB  - In recent years, methicillin-resistant Staphylococcus aureus (MRSA) isolates in
      Spain have increased dramatically; in 1986 there were only 1.2% MRSA amongst all
      nosocomial Staphylococcus aureus (SA) isolates, by 1989 this percentage had risen
      to 44% in some hospital causing a very serious epidemic situation in the country.
      We have characterized these isolates by direct, reverse and Fisk phage typing and
      we have also looked for an additional local set of phages to help us to
      differentiate these strains. We have been able to differentiate an epidemic
      strain from other MRSA strains which cause sporadic hospital outbreaks, and we
      have also distinguished between some variants of the epidemic strain.

PMID- 8150005
TI  - Cell surface hydrophobicity and adherence to extra-cellular matrix proteins in
      two collections of methicillin-resistant Staphylococcus aureus.
AB  - Non-specific and specific mechanisms of adherence have been examined in two
      collections of methicillin-resistant Staphylococcus aureus (MRSA). Determination
      of hydrophobicity by salt aggregation, hydrophobicity indices and of adherence to
      the extra-cellular matrix proteins fibronectin, vitronectin, laminin and collagen
      type 1 have failed to reveal any correlation with phage-type, plasmid profile or
      antibiogram. Further, the strain collections, made over a period of years in two
      countries, differ markedly in their adherence characteristics; MRSA are
      heterogeneous in this respect. Such heterogeneity may explain the polarization of
      views on the epidemicity or 'virulence' of MRSA. With the exception of adherence
      to collagen a small group of methicillin sensitive S. aureus had characteristics
      intermediate between the two groups of MRSA.

PMID- 8150006
TI  - Smoking, the environment and meningococcal disease: a case control study.
AB  - This case control study investigated environmental factors in 74 confirmed cases
      of meningococcal disease (MD). In children aged under 5, passive smoking in the
      home (30 or more cigarettes daily) was associated with an odds ratio (OR) of 7.5
      (95% confidence interval (CI) 1.46-38.66). ORs increased both with the numbers of
      cigarettes smoked and with the number of smokers in the household, suggesting a
      dose-response relationship. MD in this age group was also significantly
      associated with household overcrowding (more than 1.5 persons per room) (OR 6.0,
      95% CI 1.10-32.8), with kisses on the mouth with 4 or more contacts in the
      previous 2 weeks (OR 2.46, 95% CI 1.09-5.56), with exposure to dust from plaster,
      brick or stone in the previous 2 weeks (OR 2.24, 95% CI 1.07-4.65); and with
      changes in residence (OR 3.0, 95% CI 1.0-8.99), marital arguments (OR 3.0, 95% CI
      1.26-7.17) and legal disputes in the previous 6 months (OR 3.10, 95% CI 1.24
      7.78). These associations were independent of social class. Public health
      measures to lower the prevalence of cigarette smoking by parents of young
      children may reduce the incidence of MD. The influence of building dust and
      stressful life events merits further investigation.

PMID- 8150007
TI  - Nosocomial Legionnaires' disease in England and Wales, 1980-92.
AB  - Two hundred and eighteen nosocomial cases of Legionnaires' disease with 68 deaths
      were reported to the National Surveillance Scheme for Legionnaires Disease
      between 1980 and 1992, representing 15% of the reported infections acquired in
      England and Wales. Twenty-two nosocomial outbreaks accounted for 135 (62%) of
      these cases, the remainder occurring as single cases either in hospitals where
      other single cases or outbreaks had been reported in different years or as
      'sporadic' cases in hospitals from which no other cases were reported. A clinical
      history prior to onset of Legionnaires' disease was available for 124 patients,
      61 of whom had undergone recent transplant therapy or were immunosuppressed for
      other reasons. Sixty cases (27%) were diagnosed by culture of the organism and
      isolates from 56 patients were typed; 25 (42%) were non L. pneumophila serogroup
      1 infections. Methods for prevention and control of nosocomial outbreaks are
      discussed, in particular the susceptibility to Legionnaires' disease of certain
      groups of hospital patients.

PMID- 8150008
TI  - False positive legionella serology in campylobacter infection: campylobacter
      serotypes, duration of antibody response and elimination of cross-reactions in
      the indirect fluorescent antibody test.
AB  - Sera from 83 patients with campylobacter gastroenteritis were examined for the
      presence of legionella antibodies by indirect immunofluorescence. Twenty-one
      patients (25%) had positive titres (> or = 16) including 11 patients with titres
      of > or = 128. Legionella seropositivity persisted in 5 of 9 patients (55%)
      studied for 6-9 months. Campylobacter isolates were serotyped by the Penner
      scheme. Isolates associated with legionella seropositivity included Penner types
      1, 2 and 4, the common endemic serotypes in England. Campylobacter blocking
      fluids were prepared from a range of Penner reference strains. The blocking fluid
      prepared from Penner type 11 was the most efficient at inhibiting the false
      positive legionella titres. Using this absorption step legionella titres were
      inhibited from 24 of 26 patients (92%) with campylobacter but not from 8 patients
      with culture-proven legionnaires' disease. We recommend that this method is
      incorporated into routine diagnostic legionella serology in order to eliminate
      false-positive reactions due to campylobacter.

PMID- 8150009
TI  - Immunoglobulin A antibodies directed against Campylobacter jejuni flagellin
      present in breast-milk.
AB  - We studied the relationship between IgA anti-campylobacter flagellin antibodies
      in breast milk samples and protection of breastfed infants living in a rural
      Mexican village from campylobacter infection. There were fewer episodes of
      campylobacter infection (symptomatic and asymptomatic combined) in infants
      breastfed with milk containing specific anti-flagellin antibodies
      (1.2/child/year, 95% CI 0.6-1.8) versus non-breastfed children (3.3/child/year,
      95% CI 1.8-4.8; P < 0.01). Infants breastfed with milk that was anti-flagellin
      antibody negative by ELISA also had fewer episodes of infection compared with non
      breastfed children, but the difference did not reach statistical significance
      (1.8/child/year, 95% CI 0.7-3.0 versus 3.3/child/year, 95% CI 1.8-4.8, P > 0.05).
      Breastfeeding has a protective effect against campylobacter infection and is
      associated with the presence of specific antibodies directed against
      campylobacter flagellin.

PMID- 8150010
TI  - Host-microflora interaction in systemic lupus erythematosus (SLE): colonization
      resistance of the indigenous bacteria of the intestinal tract.
AB  - Experimental data suggest a role for the microflora in Systemic Lupus
      Erythematosus (SLE). Anti-ds-DNA antibodies may be pathogenic in SLE by forming
      immune complexes with DNA. Foreign bacteria in the intestines could constitute
      the stimulus for anti-ds-DNA antibody production in SLE. Colonization Resistance
      (CR) is the defence capacity of the indigenous microflora against colonization of
      the intestines by foreign bacteria. A low CR implies increase of translocation of
      bacteria and a higher chance of subsequent, possibly DNA-cross-reacting
      antibacterial antibody production. We measured CR by a comprehensive biotyping
      technique in healthy individuals and patients with inactive and active SLE. CR
      tended to be lower in active SLE patients than in healthy individuals (P = 0.09,
      Wilcoxon one sided, with correction for ties). This could indicate that in SLE
      more and different bacteria translocate across the gut wall due to a lower CR.
      Some of these may serve as polyclonal B cell activators or as antigens cross
      reacting with DNA.

PMID- 8150011
TI  - Lyme disease: a search for a causative agent in ticks in south-eastern Australia.
AB  - Attempts were made to identify the causative organism of Lyme disease in
      Australia from possible tick vectors. Ticks were collected in coastal areas of
      New South Wales, Australia, from localities associated with putative human
      infections. The ticks were dissected; a portion of the gut contents was examined
      for spirochaetes by microscopy, the remaining portion inoculated into culture
      media. The detection of spirochaetes in culture was performed using microscopy,
      and immunochemical and molecular (PCR) techniques. Additionally, whole ticks were
      tested with PCR for spirochaetes. From 1990 to 1992, approximately 12,000 ticks
      were processed for spirochaetes. No evidence of Borrelia burgdorferi or any other
      spirochaete was recovered from or detected in likely tick vectors. Some
      spirochaete-like objects detected in the cultures were shown to be artifacts,
      probably aggregates of bacterial flagellae. There is no definitive evidence for
      the existence in Australia of B. burgdorferi the causative agent of true Lyme
      disease, or for any other tick-borne spirochaete that may be responsible for a
      local syndrome being reported as Lyme disease.

PMID- 8150012
TI  - Landfill sites, botulism and gulls.
AB  - Botulism due to Clostridium botulinum type C causes considerable mortality in
      gulls in the UK, and refuse disposal sites are suspected as a major source of
      toxin. C. botulinum types B, C and D were each found in 12 (63.2%) of 19 landfill
      sites examined. Type E was detected in only one (5.2%) and types A, F and G were
      not found. The prevalence of type C spores was much higher than that demonstrated
      in the UK environment by earlier surveys. The presence of these spores, together
      with the rotting organic matter and generated heat associated with landfill
      sites, undoubtedly leads to bacterial proliferation and toxigenesis. This is
      likely to result in botulism in scavenging gulls unless skilled landfill
      management prevents the ingestion of toxic material. Type D spores were
      previously shown to be rare in the UK environment and their high prevalence on
      landfill sites was therefore surprising. Four composite samples of refuse
      collected before distribution on a landfill gave negative results for C.
      botulinum and it seems likely that the gulls themselves play a major role in
      introducing contamination.

PMID- 8150013
TI  - A study of a hospital cluster of systemic candidosis using DNA typing methods.
AB  - A cluster of disseminated Candida albicans infections, which occurred at the
      Intensive Care Unit of the Department of Heart Surgery, was investigated. Ten
      patients became infected and seven died. A wide microbiological surveillance was
      carried out. A total of 14 isolates of Candida albicans, four environmental and
      ten human, were examined using the Restriction Endonuclease Analysis (REA) of
      DNA. The isolates were classified into five different main groups. Five of the
      clinical isolates had the predominant pattern Ab and two more clinical strains
      were very closely related. Two more isolates from the emergency kit desk and the
      hands of a nurse gave the same REA profile. Such a relationship proved the
      epidemic nature of the cluster, with most of the patients cross-infected, and
      strongly suggested transmission on the hands of the staff as a determinant of the
      epidemic. Thus, REA has the potential to address many important questions in the
      study of nosocomial epidemiology of Candida albicans.

PMID- 8150014
TI  - The diagnosis of toxoplasmosis using IgG avidity.
AB  - Current methods to establish the duration of toxoplasma infection in pregnant
      women and for the diagnosis of toxoplasmosis in the neonate or HIV infected
      patient have significant limitations. We assessed the precision of a commercial
      ELISA for the detection of toxoplasma specific IgG and adapted the assay to
      measure avidity using an elution agent washing step. The sensitivity and
      specificity of the ELISA were 100 and 75% respectively and optimal measurement of
      avidity was achieved using 6 M urea as the elution agent. Toxoplasma
      lymphadenopathy of less than 3 months duration was associated with low avidity
      specific IgG but some discordant findings were recorded. Serial measurement of
      IgG avidity assisted the distinction between actively produced antibody in
      infants with congenital toxoplasmosis and passively acquired antibody of maternal
      origin in uninfected babies. There was no significant difference between avidity
      levels in HIV infected patients with or without cerebral toxoplasmosis.

PMID- 8150015
TI  - Measles vaccine: a 27-year follow-up.
AB  - In 1964, the Medical Research Council undertook a trial of measles vaccine in
      over 36,000 United Kingdom children; 9577 of whom received live vaccine, 10,625
      received inactivated followed by live vaccines, and 16,328 acted as unvaccinated
      controls. Participants in this study have been followed to determine the long
      term protection from measles vaccine and follow-up data were available on 4194,
      4638 and 274 respectively. During the 5-year period 1986-90, the protective
      efficacy of live measles vaccine has remained high at 87%, but the 95% confidence
      interval was wide (-43 to 99%) due to the small numbers of cases. Between 1976
      and 1990, however, the overall efficacy of the live vaccine was 92% (95%
      confidence interval 86 to 95%) and there was no evidence of a decline in efficacy
      (P = 0.13) over the 15-year period. This study suggests that the protection from
      live measles vaccine persists for up to 27 years after vaccination, and that no
      change in the current United Kingdom measles immunization policy should be made
      on the grounds of waning immunity.

PMID- 8150017
TI  - Antigenicity and immunogenicity of equine influenza vaccines containing a
      Carbomer adjuvant.
AB  - Equine influenza vaccines containing inactivated whole virus and Carbomer
      adjuvant stimulated higher levels and longer lasting antibody to haemagglutinin
      in ponies than vaccines of equivalent antigenic content containing aluminium
      phosphate adjuvants. Five months after the third dose of vaccine containing
      Carbomer adjuvant, ponies were protected against clinical disease induced by an
      aerosol of virulent influenza virus (A/equine/Newmarket/79, H3N8). In contrast
      ponies which received vaccine containing aluminium phosphate adjuvant were
      susceptible to infection and disease. There was an inverse correlation between
      prechallenge levels of antibody detected by single radial haemolysis (SRH) and
      duration of virus excretion, pyrexia and coughing. All ponies with antibody
      levels equivalent to SRH zones of > or = 154 mm2 were protected against infection
      and all those with levels > or = 85 mm2 were protected from disease.

PMID- 8150016
TI  - Long-term survival in trial of medium-titre Edmonston-Zagreb measles vaccine in
      Guinea-Bissau: five-year follow-up.
AB  - A trial of protective efficacy which compared medium-titre Edmonston-Zagreb (EZ)
      measles vaccine (10(4.6) p.f.u.) from the age of 4 months with the standard
      Schwarz (SW) measles vaccine given from the age of 9 months was started in an
      urban community in Guinea-Bissau in 1985. Because trials of high-titre measles
      vaccine have found increased mortality among female recipients, we examined
      whether EZ medium-titre vaccine was associated with any long-term impact on
      mortality, suppression of T-cells, or growth. The mortality rate ratio over 5
      years of follow-up was 1.12 for EZ children compared with children in the
      standard group (P = 0.63). Seventy-five percent of the children still residing in
      the area at 5 years of age took part in an immunological and anthropometric
      examination. There was no difference in T-cell subsets between the two groups.
      There was no difference in mid-upper-arm circumference, but EZ children were
      significantly shorter than the children in the standard group. In conclusion,
      medium-titre EZ was not associated with reduced survival or persistent
      immunosuppression.

PMID- 8150018
TI  - Lens sodium channels are inactivated by anti-MIP26 antibodies.
AB  - Sodium-specific channels can be functionally identified in phosphatidylcholine
      liposomes incorporating detergent-solubilized membrane proteins from pig lens
      epithelium and outer cortex. The transport of sodium is saturable, specific and
      protease-sensitive. MIP26 was identified in the solubilized membrane fraction and
      in the liposomes by means of Western blot analysis. Pre-treatment of liposomes
      with anti-MIP26 antiserum abolished the transport of sodium. These data indicate
      that MIP26 is associated to a sodium selective transport activity.

PMID- 8150019
TI  - The prevention of cataract caused by oxidative stress in cultured rat lenses. II.
      Early effects of photochemical stress and recovery.
AB  - Previous work has demonstrated that photochemically induced oxidative stress
      generated with 4 microM riboflavin in a 4% oxygen atmosphere utilizing daylight
      type radiation is capable of causing cataract in cultured rat lenses. Such
      cataract is prevented by the GSH peroxidase type mimic, AL-3823A. Examination of
      the early stages of cataract formation produced by short-term oxidative stress
      and recovery is now reported. A 24-hr oxidative stress, under the above
      conditions, causes loss of transparency, particularly in the equatorial region,
      increased hydration, loss of glyceraldehyde-3-PO4 dehydrogenase activity,
      oxidation of non-protein thiol and a decrease in 86Rb and [14C]choline uptake and
      ATP levels. Examination of recovery of these parameters during a 72-hr period
      indicates, in most cases, little or no reversal of oxidative damage. Hydration
      and loss of non-protein thiol continued during the recovery period. The presence
      of AL-3823A during the stress period prevented change in all parameters.
      Transport systems appear to be particularly vulnerable to this type of oxidative
      stress losing 50% or more activity within 4 hr. Even after a 2-hr stress, choline
      transport did not recover even though, under these conditions, ATP levels had
      only decreased slightly. Cytosolic components such as non-protein thiol and
      glyceraldehyde-3-PO4 dehydrogenase also showed little change after a 4-hr insult.
      86Rb efflux experiments indicated no change in permeability during a 24-hr stress
      period. The overall conclusion from these studies is that a 24-hr oxidative
      stress which appears to reflect physiological conditions existing during cataract
      development, causes extensive, irreversible damage.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8150020
TI  - A versatile perifusion system for the NMR spectroscopy of bovine retina.
      Assignment of resonances and effect of ischemia.
AB  - A perifusion system has been designed for metabolic nuclear magnetic resonance
      (NMR) spectroscopy studies of the bovine retina. This system, which allows the
      use of unmodified commercial probes for multinuclear studies, is shown here to
      maintain the perifused retina in a metabolic steady state at 25 degrees C, as
      deduced from its 31P and 1H NMR spectra. The 31P NMR ex vivo spectrum of the
      retina has been characterized, and its major resonances have been assigned in
      tissue extracts. We have found that excised retinal tissue subjected to 2 hr of
      ischemia is capable, upon perifusion with oxygenated medium, of recovering its
      resting spectral pattern. Thus, this system offers a versatile model for studies
      of physiological events related with ischemia in a neural tissue, without
      associated systemic effects.

PMID- 8150021
TI  - Identification of cyclic nucleotide-regulated phosphoproteins, including
      phosducin, in motile rod inner-outer segments of teleosts.
AB  - In teleost retinas, rods elongate in the light and shorten in the dark. Rod
      motility is mediated by the actin cytoskeleton of the inner segment and is
      regulated by cyclic AMP- or cyclic GMP-stimulated phosphorylation of target
      proteins. In this study, we have identified the target proteins of cyclic
      nucleotide-dependent kinases in rods, using preparations of isolated, motile rod
      inner-outer segments (RIS-ROS). Five proteins found in Percoll-purified RIS-ROS
      were phosphorylated in the presence of cAMP (> 10 nM), cGMP (> or = 10 microM)
      and exogenous catalytic subunit of cAMP-dependent protein kinase (PKA). The PKA
      inhibitor, PKI, blocked stimulation of phosphorylation by both cAMP and cGMP.
      Three cAMP-stimulated phosphoproteins were detected in cytoskeletal fractions of
      light- and dark-adapted RIS-ROS. One of these, PP33, appears to be a fish
      homologue of mammalian phosducin, based on immunolabeling by two different
      antibodies against mammalian phosducin and on electrophoretic characteristics in
      2-D gels. Two additional phosducin immunoreactive bands were detected in Western
      blots. One, at 35 kDa, comigrated with a second cAMP-stimulated RIS-ROS
      phosphoprotein, PP35, which was also detected in the cytoskeleton. The other, at
      37 kDa, was present in whole teleost retinas but not in purified RIS-ROS. Our
      results suggest that the effects of both cAMP and cGMP on teleost rod motility
      are mediated through PKA modulation of target phosphoproteins. These
      phosphoproteins include a cytoskeleton-associated phosducin homologue.

PMID- 8150022
TI  - Protein kinase C regulation of a Na+, K+, Cl- cotransporter in fetal human
      pigmented ciliary epithelial cells.
AB  - The epithelium of the ciliary body is the site of aqueous humor secretion in the
      eye. We have begun to study ion transport in this tissue by investigating the
      mechanisms of K(+)-transport in fetal human pigmented ciliary epithelial (PE)
      cells using 86Rb+ as a tracer for K+. In PE three mechanisms were found: (1)
      ouabain-sensitive, bumetanide-insensitive 86Rb+ uptake (approximately 70% of
      total); (2) bumetanide-sensitive, ouabain-insensitive 86Rb+ uptake (approximately
      15% of total); and (3) K+ channel blocker-sensitive 86Rb+ uptake (approximately
      15% of total). Evidence that the ouabain-insensitive component of 86Rb+ uptake
      includes a Na+, K+, Cl- cotransporter is the following: (1) bumetanide inhibited
      86Rb+ uptake with an IC50 of 0.6 microM and (2) bumetanide-sensitive 86Rb+ uptake
      was substantially reduced in media lacking Na+ or Cl-, suggesting that both
      extracellular Na+ and Cl- are required for optimal 86Rb+ uptake via this
      mechanism. Treatment of cells for 15 min with phorbol 12-myristate, 13-acetate
      (PMA) caused a dose-dependent inhibition of bumetanide-sensitive 86Rb+ uptake. No
      other 86Rb+ uptake mechanism was affected. Efflux studies revealed that efflux
      via the bumetanide-sensitive mechanism was likewise inhibited by PMA. Treatment
      with other phorbol esters or an analog of diacylglycerol inhibited bumetanide
      sensitive 86Rb+ uptake, while the protein kinase C inhibitor staurosporine
      blocked inhibition by phorbol esters. These data suggest that a Na+, K+, Cl-
      cotransporter in human PE cells is inhibited activation of protein kinase C.

PMID- 8150023
TI  - Retinomotor movements in isolated teleost retinal cone inner-outer segment
      preparations (CIS-COS): effects of light, dark and dopamine.
AB  - Teleost cone inner segments elongate and contract in response to light and
      circadian signals. Previous studies have shown that teleost cone contraction is
      triggered by light or dopamine, while cone elongation is triggered by darkness or
      experimental elevation of cAMP. We have developed procedures for isolating and
      purifying motile cone fragments consisting of inner and outer segments (CIS-COS)
      to permit more detailed analysis of light and dopamine regulation of cone
      retinomotor movements. When retinas are dissected from long-term dark-adapted
      fish, CIS-COS break off at the base of the ellipsoid and remain attached to the
      RPE. CIS-COS can be detached from the RPE by brief protease treatment, thereby
      generating a highly enriched CIS-COS suspension. CIS-COS retain normal morphology
      and extend new myoids when cultured in darkness or in light plus forskolin, an
      activator of adenylate cyclase. The microtubule and actin cytoskeletons of the
      new myoids resemble those of intact cone myoids in vivo. Light inhibits CIS-COS
      myoid elongation, suggesting that light reception by the outer segment can
      directly influence cone motility. In dark-cultured CIS-COS, myoid elongation is
      inhibited half-maximally by nanomolar concentrations of dopamine, suggesting that
      dopamine effects on motility are mediated by D2-family receptors present on the
      cone inner and/or outer segment. After dark-induced elongation in culture, CIS
      COS myoids can be induced to contract by subsequent culture in the light or with
      dopamine. Thus isolated cone inner and outer segments possess sufficient
      cytoskeletal and regulatory machinery to exhibit light- and dopamine-regulation
      retinomotor movement similar to that observed in intact cones in situ.

PMID- 8150024
TI  - Electron microscopic immunocytochemical evidence for the mechanism of blood
      retinal barrier breakdown in galactosemic rats and its association with aldose
      reductase expression and inhibition.
AB  - Blood-retinal barrier (BRB) breakdown occurs in human diabetic retinopathy and
      can lead to significant loss of vision. The galactosemic rat serves as a model
      for human diabetic retinopathy and develops many of the same ocular
      complications, including BRB failure. Aldose reductase (AR), an enzyme in the
      polyol pathway, has been implicated in several of these complications. Electron
      microscopic immunocytochemical staining for albumin can be used to visualize
      extravasated albumin in control and galactosemic rats with and without AR
      inhibition to reveal the mechanism for galactosemia-related BRB failure without
      the use of tracer substances, and to determine whether AR activity influences
      this mechanism. Electron microscopic immunocytochemical labeling of AR can reveal
      the cellular distribution of AR in normal and galactosemic rat retina and
      determine whether a correlation exists between BRB breakdown and AR expression in
      cells that form or influence the BRB. Extravascular albumin is demonstrable as
      early as 2.5 months in galactosemic rats, which is prior to the presentation of
      ultrastructural changes. Albumin-positivity is visualized in retinal vascular
      endothelial (RVE) cell cytoplasm from galactosemic rats both diffusely and within
      vesicles, but it is not detected in comparably aged normal rat RVE cells or
      within the tight junctions of the RVE or RPE (the cells that form the BRB) in
      control or galactosemic rats, suggesting that BRB breakdown in galactosemic rats
      may be mediated through two mechanisms: a permeation of the RVE cell membrane
      leading to diffuse cytoplasmic positivity for albumin, and vesicular transport
      across the RVE. The AR inhibitor, sorbinil, prevents diffuse cytoplasmic staining
      of RVE cells, but not vesicular staining, implying that RVE membrane permeability
      may be altered by AR activity, but vesicle formation does not appear to be
      affected. AR was immunocytochemically demonstrated in some RVE cells from
      galactosemic rats, but not from controls. In perivascular astrocytes, which may
      influence the integrity of the inner BRB, AR labeling was augmented in
      galactosemic rats. Increased AR expression in RVE cells and perivascular
      astrocytes from galactosemic rats provides additional support for a role for AR
      in galactosemia-related BRB failure.

PMID- 8150025
TI  - Calcium activated proteolysis and protein modification in the U18666A cataract.
AB  - Proteolytic modifications of specific water soluble lens crystallins during
      U18666A cataract formation in young rats were identified by two dimensional gel
      electrophoresis and contrasted with those produced by incubating control lens
      homogenates with calcium. Protein changes which began in clear precataractous
      lenses at 12 days age included a decrease in 31 and 27 kDa (likely to be beta B1a
      and beta A3, respectively) crystallin polypeptides, increase in 25 kDa basic
      polypeptide, appearance of new polypeptide at 30 kDa and modification of alpha A
      crystallin. Further modification of both alpha- and beta-crystallins occurred as
      cataracts formed; they progressed from early to advanced stage within a span of 4
      days. During this period polypeptides beta B1a and beta A3 almost completely
      disappeared and several new components of 23-26 kDa in beta-crystallin region
      appeared. Extensive modification of alpha A resulted in appearance of new
      components of less than 20 kDa. Most of the gamma-crystallins disappeared from
      the water soluble proteins in advanced cataract lenses of 18 day old rats
      presumably by leaking out of the lens. The water insoluble proteins which
      accumulated in the cataract were very similar to modified crystallins which
      appeared in the water soluble fraction. In vitro incubation of normal lens water
      soluble proteins with calcium duplicated most of the protein changes seen during
      cataract progression. Immunoblotting studies with antisera to rat alpha- and beta
      crystallins revealed the identity of most of the modified water soluble
      proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150026
TI  - DL-propranolol inhibits lens hexokinase activity and affects lens optics.
AB  - A clinico-biochemical study indicated that the beta-blocker DL-propranolol may
      affect human lens epithelial hexokinase (HK) activity. In that study five key
      enzymes were analysed in 192 freshly excised human lens epithelia obtained during
      cataract surgery. In a large number of patients the epithelial HK was found to be
      inactive. Medical records of these patients showed widespread use of the drug DL
      propranolol. In vitro experiments demonstrated a direct inhibitory effect of the
      drug on human lens HK activity. Lens refractive function was monitored during
      long term bovine lens culture experiments in which the potential cataractogenic
      agent was added to the culture media. DL-propranolol in a concentration of 0.1 mM
      reduced HK activity in bovine lens epithelium after 72 hr in organ culture and
      disrupted lens light focusing ability after 250 hr of incubation. Kinetic studies
      of HK inhibition suggested a competitive inhibitory effect of the drug on the
      enzyme.

PMID- 8150027
TI  - Effects of RPE age and culture conditions on support of photoreceptor cell
      survival in transplanted RCS dystrophic rats.
AB  - This study assessed the effects of transplants of freshly isolated or cultured
      (ie. passaged) retinal pigment epithelial (RPE) cells from neonatal and adult
      normal and RCS pigmented dystrophic rats on photoreceptor cell survival in
      retinas of 22-26-day-old pink-eyed RCS dystrophic rats. We determined that
      retinas of 2-month-old RCS rats transplanted at 26 days with RPE cells of adult
      RCS rats did not support photoreceptor cell survival above that seen in sham or
      nontreated control RCS retinas, as outer nuclear layer (ONL) thicknesses were not
      significantly different (10.0 +/- 1.31 microns, 11.7 +/- 4.04 microns and 9.42 +/
      1.88 microns, respectively). Surprisingly, in this same transplant group, RPE
      transplants from neonatal RCS dystrophic rats were able to promote photoreceptor
      cell survival similar to that seen in transplants of neonatal Long Evans rats, as
      evidenced by similar ONL thicknesses (34.4 +/- 3.16 microns and 33.6 +/- 6.03
      microns, respectively), but the rescue effect quickly diminished. However, in
      retinas of 22-26-day-old RCS rats transplanted with RPE cells from adult Long
      Evans rats, the level of photoreceptor cell rescue was approximately 48% (ONL:
      19.6 +/- 2.79 microns), when compared to retinas transplanted with RPE cells from
      neonatal Long Evans rats, but significantly greater than that caused by
      transplants of RPE cells from adult RCS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150028
TI  - Expression of recoverin mRNA in the human retina: localization by in situ
      hybridization.
AB  - The localization of mRNA encoding recoverin in the human retina was examined by
      in situ hybridization. The riboprobe utilized in this study was transcribed from
      a cDNA clone containing the complete coding region of human recoverin. The
      riboprobe hybridized extensively with the photoreceptor inner segments, and the
      outer nuclear layer. Specific hybridization was also seen in a subpopulation of
      cells in the inner nuclear layer, and occasionally in cells of the ganglion cell
      layer (GCL). Recoverin-like immunoreactivity was observed in all photoreceptors,
      and in a subpopulation of bipolar cells. Very robust immunolabeling was observed
      in a small population of cells in the GCL. This study suggests that recoverin, or
      a recoverin-like protein, is produced by at least three different cell types in
      the human retina: photoreceptors, bipolars and rare cells in the ganglion cell
      layer.

PMID- 8150029
TI  - Interphotoreceptor retinoid binding protein (IRBP) enhances rhodopsin
      regeneration in the experimentally detached retina.
AB  - Results obtained in a previous study showed that, compared with a normal eyecup
      preparation, the amount of rhodopsin regenerated and the rate at which it was
      resynthesized after bleaching were reduced by about 50% when the skate retina was
      detached from its pigment epithelium (RPE) and replaced immediately on the apical
      surface of the RPE (Sun and Ripps, 1992). In the present study, these
      observations have been extended to preparations in which the detachment procedure
      was performed under fluid in order to dilute the IRBP content of the
      interphotoreceptor matrix. The goal initially was to determine whether lowering
      the IRBP concentration of the subretinal space affected the regenerative process.
      Using fundus reflectometry, it was found that allowing fluid to enter the
      subretinal space exposed by the detachment procedure caused profound deficits in
      both the rate and amount of rhodopsin that regenerated after bleaching. Results
      obtained with SDS-PAGE and immunohistochemistry showed that the molecular weight
      of the IRBP extracted from the skate retina is similar to that of many other
      vertebrate species, and that antibodies prepared against mammalian IRBP react
      with epitopes on skate IRBP within the interphotoreceptor matrix. Accordingly, it
      was investigated whether it is possible to reverse the detachment-induced
      anomalies in rhodopsin kinetics by introducing ligand-free IRBP purified from
      bovine retina to the subretinal space. Again using fundus reflectometry, it was
      found that instilling 5 microM of a 130 microM IRBP solution between the neural
      retina and the RPE increased significantly the rate of regeneration, and more
      than doubled the amount of rhodopsin reformed in darkness.

PMID- 8150030
TI  - Increased susceptibility to metal catalysed oxidation of diabetic lens beta L
      crystallin: possible protection by dietary supplementation with acetylsalicylic
      acid.
AB  - The effect of dietary supplementation with acetylsalicylic acid on the increased
      modification, and susceptibility to modification, of lens crystallins from the
      streptozocin diabetic rat, has been determined. This was done by the measurement
      of characteristic markers of protein post-translational oxidative modification
      and glycation, in beta L crystallins purified from the lenses of control,
      diabetic and acetylsalicylic acid-supplemented diabetic animals, with no further
      manipulations, and again following the application of an in vitro graded
      oxidative insult. Crystallins prepared from the diabetic, in comparison with
      control animals, exhibited a higher level of bityrosine- and AGEP-like
      fluorescence as well as a loss of tryptophan fluorescence and sulphydryl groups.
      Exposure to an oxidative insult (in the form of CuSO4 and ascorbate) increased
      all parameters in beta L crystallins, irrespective of their source. However, the
      effects were most pronounced in the diabetic in which the effects of oxidative
      stress were always greater than the control crystallin. Dietary supplementation
      of the diabetic group with acetylsalicylic acid (100 mg kg-1 body weight day-1)
      had a marked effect in decreasing the level of modification induced in diabetic
      crystallins, by in vitro metal catalysed oxidative stress, lowering the levels of
      AGEP- and bityrosine-like fluorescence and carbonyl group formation. Increasing
      the oxidative stress by addition of increasing concentrations of H2O2, induced
      stress proportional increases in the indicators of protein modification in all
      beta L crystallins, irrespective of source. The increase in damage in relation to
      H2O2 concentration was greater in those crystallins from diabetic animals,
      revealing a greater susceptibility to such oxidative stress.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8150031
TI  - Uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis
      in the Lewis rat.

PMID- 8150032
TI  - The autonomous release of erythropoietic inhibition during long-term in vivo
      administration of actinomycin D.
AB  - In this study, we describe the effect of actinomycin D (Act D), 120 micrograms/kg
      every 2 days, on hematopoiesis over a 48-day period. Erythropoiesis is almost
      totally eradicated by day 6. Despite continued Act D treatment, however, the
      block in differentiation between the early (burst-forming units-erythroid [BFU
      E]) and late (colony-forming units-erythroid [CFU-E]) erythropoietic progenitor
      populations is overcome, giving rise to a synchronized and periodic
      erythrocytosis in both bone marrow and spleen. The first peak is seen on day 27,
      followed by a second peak on day 41. Circulating erythropoietin (Epo) levels
      increase from days 16 to 34, indicating that Act D does not have an effect on Epo
      production. Increasing endogenous Epo levels by bleeding results in an earlier
      erythroblast and 59Fe incorporation peak than in unbled animals. The BFU-E
      population increased in number until the block between BFU-E and CFU-E was
      overcome. No apparent change occurred in either the day 8 colony-forming units
      spleen (CFU-S day 8) or granulocyte-macrophage colony-forming cells (GM-CFC) in
      the bone marrow, although a dramatic increase in GM-CFC in the spleen was
      observed. It appears that release from the Act D-induced block in differentiation
      may, in part, be due to Epo, but the mechanism by which this phenomenon takes
      place is unclear.

PMID- 8150033
TI  - Synergistic effects of interleukin-11 with other growth factors on the expansion
      of murine hematopoietic progenitors and maintenance of stem cells in liquid
      culture.
AB  - The effect of interleukin-11 (IL-11), alone and in combination with other
      hematopoietic growth factors, was studied in liquid suspension cultures of murine
      bone marrow. Stem and progenitor cell contents of input bone marrow 2 days after
      5-fluorouracil (5-FU) treatment (FU2dBM) and lineage-depleted, Sca-1-positive
      FU2dBM (Lin-Sca+Fu2dBM) were compared with output values obtained after 6 days in
      different growth factor combinations. Stem and progenitor cell recoveries were
      measured by long-term in vivo competitive repopulation, spleen colony-forming
      unit (CFU-S), and in vitro limiting dilution long-term bone marrow culture
      (cobblestone area-forming cell [CAFC]) assays. IL-11, IL-3, IL-6, and Steel
      factor (SF) were tested separately and in combinations of two, three, and four
      factors. IL-11 was incapable of maintaining the survival of stem or progenitor
      cells as a single agent but synergized with either IL-3 or SF to expand
      progenitor cell output in cultures of FU2dBM. IL-11 greatly enhanced progenitor
      cell expansion from FU2dBM when added to two- and three-factor combinations of
      SF, IL-3, and IL-6. The recovery of long-term repopulating ability was enhanced
      four-fold by incubation in SF plus IL-11 compared to SF alone. IL-11 in
      combination with SF, IL-3, and IL-6 stimulated a 24,000-fold expansion of
      progenitor cells from stem cell-enriched Lin-Sca+FU2dBM. Overall, the results
      indicate that IL-11 is a potent synergistic factor for stem cell proliferation
      and expansion of progenitors in liquid culture.

PMID- 8150035
TI  - Alteration of the proteoglycan form of macrophage colony-stimulating factor
      produced by a human stromal line stimulated by tumor necrosis factor-alpha.
AB  - Immunoblot analysis of macrophage colony-stimulating factor (M-CSF) in KM 102
      cell-conditioned medium showed the presence of two M-CSF molecular types, one
      being 85-kd M-CSF, the other a proteoglycan form (PG-M-CSF) carrying a
      chondroitin sulfate chain of variable length. When KM 102 cells were stimulated
      by TNF-alpha, they produced more M-CSF than that produced in unstimulated
      condition, in which PG-M-CSF had a shorter chondroitin sulfate chain. Although PG
      M-CSF has binding affinity for type V collagen, the PG-M-CSF with the shorter
      chondroitin sulfate chain shows lower affinity. This spreads in type V collagen
      containing agarose gel more easily than does PG-M-CSF with a longer chondroitin
      sulfate chain.

PMID- 8150034
TI  - Ciprofloxacin enhances hematopoiesis and the peritoneal neutrophil function in
      lethally irradiated, bone marrow-transplanted mice.
AB  - We analyzed the effect of in vivo ciprofloxacin and ceftazidime treatment on the
      development of myeloid progenitors and on the survival of lethally irradiated
      mice rescued with syngeneic bone marrow transplantation (BMT). Ciprofloxacin
      treatment (15 mg/kg per dose three times daily for 5 days) enhanced myeloid
      progenitor (colony-forming cell [CFU-C]) number in the bone marrow and the
      survival of mice transplanted with suboptimal doses (1 x 10(5) of s[Ngeneic bone
      marrow cells (BMC). Twenty days postirradiation, 50% (38 of 76) of saline-treated
      mice transplanted with 1 x 10(5) cells died compared with 25% (19 of 76) of
      ciprofloxacin-treated mice (p < 0.05). Similarly, ciprofloxacin treatment
      enhanced survival of mice transplanted with 1 x 10(6) syngeneic bone marrow
      cells: 50% (38 of 76) of saline-treated mice died within 20 days vs. 15% (12 of
      80) of ciprofloxacin-treated mice. In contrast, treatment with ceftazidime did
      not affect progenitor cell number or survival. On day 8 postirradiation, although
      lethally irradiated mice transplanted with 1 x 10(5) BMC treated with
      ciprofloxacin demonstrated similar white blood cell (WBC) and red blood cell
      (RBC) counts as saline-treated mice, a (1.9 +/- 0.2)-fold increase in the
      percentage of polymorphonuclear cells (PMN) was observed in the peripheral blood
      of ciprofloxacin-treated mice. On day 5 postirradiation, ciprofloxacin-treated
      mice showed a (1.6 +/- 0.2)-fold increase in the number of peritoneal PMN and a
      6.5-fold increase in their antibacterial activity towards Salmonella typhimurium
      in comparison with saline-treated mice.

PMID- 8150036
TI  - Evidence suggesting a negative regulatory role for macrophages in murine
      erythropoiesis in vivo.
AB  - Increasing the rate of erythropoiesis in C57BL/6 mice, either by hypoxia or by
      the injection of recombinant erythropoietin (Epo), resulted in significant
      reductions in marrow macrophage number, as assessed by flow cytometry employing
      the monoclonal antibody against the macrophage antigen Mac-1 and by histologic
      determination of reductions in the number of marrow esterase-positive cells. This
      decline was paralleled by decreases in marrow colony-forming unit-macrophage (CFU
      M) and colony-forming unit-granulocyte/macrophage (CFU-GM) number. The
      intramedullary concentration of the cytokines interleukin-1 alpha (IL-1 alpha)
      and tumor necrosis factor-alpha (TNF-alpha), which are produced by macrophages,
      was also reduced. Cessation of erythropoiesis was associated with increases in
      macrophage number, CFU-M and CFU-GM colony number, and IL-1 alpha concentrations.
      Increased erythropoiesis resulted in reductions in number of burst-forming unit
      erythroid (BFU-E) colonies, which were less sensitive to suppression by
      macrophages as evidence by less increase in colony number when macrophages were
      removed from the marrow before in vitro BFU-E culture. BFU-E colony number was
      suppressed less when IL-1 alpha and TNF-alpha were added to cultures obtained
      from animals with stimulated erythropoiesis. Compared to controls, BFU-E number
      and suppression by macrophages increased significantly when erythropoiesis was
      reduced. These observations provide compelling evidence for a regulatory role for
      macrophages in normal erythropoiesis in vivo, presumably acting as a negative
      balance to the stimulatory effects of Epo.

PMID- 8150037
TI  - Age-related changes in extramedullary hematopoiesis in the spleen of normal and
      perturbed osteopetrotic (op/op) mice.
AB  - Occlusion of the marrow cavity by excessive bone formation in young osteopetrotic
      (op/op) mice results in a significant reduction in the space available for
      hematopoiesis. At this time, splenomegaly is evident, and the spleen is a site of
      significant extramedullary hematopoiesis. In vitro clonal assays of spleen cell
      suspensions in young op/op mice demonstrated a 22-fold elevation in the content
      of high proliferative potential colony-forming cells (HPP-CFC) (4 weeks of age)
      and a 14-fold elevation in the content of committed progenitors responsive to
      colony-stimulating factor-1 (CSF-1) (6 weeks of age). Flow-cytometric analysis
      also demonstrated a shift in the myeloid:lymphoid cell ratio in the spleens of
      young op/op mice, with a 35% reduction in the number of B220+ cells, and a two
      fold increase in myeloid cells expressing the hematopoietic cell surface lineage
      antigens Mac-1 and Gr-1. However, the hematopoietic deficiencies of op/op mice
      are not permanent. An age-related progressive remodeling of the bone marrow
      cavity results in the correction of bone marrow parameters by 22 weeks of age.
      This correction in marrow hematopoietic activity is accompanied by a resolution
      of the splenomegaly, a progressive decrease in splenic hematopoietic activity at
      both the primitive and committed progenitor cell levels, and a correction of the
      lymphoid:myeloid cell ratio. Negative immunomagnetic selection of splenic
      hematopoietic progenitor cells from op/op and control littermate mice, followed
      by analysis of their expansion in liquid culture, demonstrated that primitive
      hematopoietic progenitor cells of high proliferative potential continued to
      reside in the spleen of old op/op mice. The response of these mice to a 5
      fluorouracil (5-FU) cytotoxic challenge suggested that this pool of primitive
      progenitor cells acted as a hematopoietic reserve capable of rapidly responding
      to hematopoietic perturbation.

PMID- 8150038
TI  - Erroneous results of 3H-thymidine incorporation are related to position of
      thymidine residues in oligodeoxynucleotides.
AB  - Antisense oligodeoxynucleotides (ODNs) targeted to complementary mRNA sequences
      have proved to be a powerful approach in assessing the function and the role of
      unique genes in cell proliferation, differentiation, or transformation. Despite
      their importance in the development of future therapies, little is known about
      their fate after uptake by cells. Here, we have examined the contribution of
      individual nucleotide residues from synthetic nonspecific ODNs on assays commonly
      used to measure cell proliferation. A dramatic decrease of the 3H-thymidine (3H
      T) incorporation was obtained with nonspecific ODNs, while no effect on cell
      proliferation was observed as assessed by three other techniques. We demonstrate
      that the presence and position of thymidine in the ODNs directly interfere with
      the intracellular thymidine pool, leading to faulty data of 3H-T incorporation.
      As an alternative method, we used 3H-deoxyuridine (3H-dU), which is integrated
      more efficiently in DNA than thymidine. We observed that 3H-dU incorporation was
      also decreased. In conclusion, caution should be exercised in the interpretation
      of the results of 3H-T and 3H-dU incorporation in the presence of
      oligodeoxynucleotides.

PMID- 8150039
TI  - Meeting on negative regulation of hematopoietic cell growth and differentiation.

PMID- 8150040
TI  - Hematopoietic cytokines enhance survival of SCID mice undergoing high-dose
      irradiation.

PMID- 8150041
TI  - Upregulation of fibroblast growth factor-receptor messenger RNA expression in rat
      brain following transient forebrain ischemia.
AB  - Recently, we demonstrated that transient forebrain ischemia in rats leads to an
      early and strong induction of basic fibroblast growth factor (bFGF) synthesis in
      astrocytes in the injured brain regions. In this study, in order to clarify the
      targets of such raised endogenous bFGF levels, the messenger RNA (mRNA)
      expression of its receptors (flg and bek) in the hippocampus following transient
      forebrain ischemia induced by four-vessel occlusion for 20 min was investigated
      using an in situ hybridization technique. Transient forebrain ischemia induced an
      increase in the number of flg mRNA-positive cells from an early stage (24 h after
      ischemia) in the hippocampal CA1 subfield where delayed neuronal death occurred
      later (48-72 h after ischemia). This increase became more marked with the
      progression of neuronal death and was still evident in the same area 30 days
      later. The time course of the appearance and distribution pattern of flg mRNA
      positive cells in the CA1 subfield were quite similar to those of bFGF mRNA
      positive cells. On the other hand, in situ hybridization for bek mRNA showed only
      slight and transient (observed 72 h and 5 days after ischemia) increases in the
      number of mRNA-positive cells in the CA1 subfield following ischemia. The use of
      in situ hybridization and glial fibrillary acidic protein immunohistochemistry in
      combination demonstrated that the cells in the CA1 subfield that exhibited
      ischemia-induced flg or bek mRNA expression were astrocytes. These data indicate
      that transient forebrain ischemia induces upregulation of fibroblast growth
      factor-receptor expression, accompanied by increased bFGF expression in
      astrocytes, and suggest that the increased astrocytic bFGF levels in injured
      brain regions act on the astrocytes via autocrine systems and are involved in the
      development and maintenance of astrocytosis.

PMID- 8150042
TI  - Effects of nucleus basalis lesion on muscarinic receptor subtypes.
AB  - The cholinergic system in the central nervous system is an important component of
      the neural circuitry of learning, memory and cognition. A decline of cholinergic
      innervation in the human brain is a characteristic feature of dementia of
      Alzheimer's type. In this study, changes in cholinergic markers were studied
      after a unilateral lesion of the nucleus basalis magnocellularis (nbM).
      Acetylcholinesterase (AChE) histochemistry showed a loss of cortical AChE
      containing neurons, and choline acetyltransferase (ChAT) immunohistochemistry
      demonstrated a loss of cholinergic cells in nbM. The localizations of muscarinic
      M1 and M2 receptors using [3H]pirenzepine ([3H]PZ) and [3H]AF-DX 384,
      respectively, were studied by quantitative autoradiography 1, 2, 4 and 6 weeks
      following unilateral ibotenic acid lesion of nbM. A significant decrease in
      [3H]PZ binding sites was observed at postlesion week 1 in the parietal and
      temporal cortices. The decrease in [3H]AF-DX 384 binding sites on the lesioned
      side was observed throughout frontal, parietal and temporal cortices after
      postlesion week 1, with a significant increase after 6 weeks, possibly as result
      of loss of presynaptic receptors and upregulation of postsynaptic ones. Moreover,
      laminar distribution after nbM lesion shows that M1 and M2 receptor binding sites
      are more affected in superficial layers (I,II,III) than in the deep layers
      (IV,V,VI), depending on ligand, postlesion period and cortical region.
      Furthermore, nbM lesion causes a higher deficit of M2 receptors than of M1
      receptors. These data suggest the existence of a presynaptic population as well
      as a postsynaptic population of M1 and M2 receptors which are differently
      affected after unilateral nbM lesion.

PMID- 8150043
TI  - The effects of HA1077, a novel protein kinase inhibitor, on reductions of
      cerebral blood flow and glucose metabolism following acute and/or chronic
      bilateral carotid artery ligation in Wistar rats.
AB  - The effects of HA1077, a novel protein kinase inhibitor on local cerebral blood
      flow (LCBF) 2.5 h (acute) after permanent bilateral carotid artery ligation
      (BCAL) and on LCBF and local cerebral glucose utilisation (LCGU) one week
      (chronic) after BCAL were studied in conscious Wistar rats. Use was made of
      quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose
      techniques and 24 anatomically discrete regions of the brain. HA1077 (1 or 3
      mg/kg) or saline was infused i.v. over a 30 min period. HA1077 significantly
      increased LCBF after acute BCAL in one of the 23 decreased regions in rats given
      1 mg/kg, and in 14 of 23 decreased regions in rats given 3 mg/kg, compared to
      findings in the saline-treated group. Significant increases in LCBF and LCGU
      after chronic BCAL were noted in seven of the 13 decreased regions and in four of
      the 11 decreased regions in rats given 3 mg/kg, as compared to observations in
      the corresponding saline-treated group, respectively. The LCBF and LCGU
      reductions in forebrain regions with global ischaemia after acute and/or chronic
      BCAL were overcome by HA1077. These results suggest that HA1077 may be considered
      for treatment of subjects with acute and chronic cerebral ischaemia, with
      impairment in cerebral circulation and/or glucose metabolism.

PMID- 8150044
TI  - Saccadic eye movements and the horizontal vestibulo-ocular and vestibulo-collic
      reflexes in the intact guinea-pig.
AB  - The guinea-pig is an attractive model for investigating gaze stabilization
      because it is suitable for in vitro and in vivo studies. However, few data are
      available on its oculomotor performance. We therefore investigated spontaneous
      eye movements, horizontal vestibulo-ocular (HVOR) and vestibulo-collic reflexes
      (HVCR) in the alert head-fixed guinea-pig using the magnetic search coil method.
      First the characteristics of the spontaneous saccades in the light were analysed.
      They occurred with a mean frequency of 4.6/min and with a mean amplitude and
      duration of 7.41 +/- 3.57 deg and 30.9 +/- 9.5 ms, respectively (n = 340).
      Saccadic duration and velocity were linearly related to the amplitude of the eye
      movement. The HVOR was studied in response to sinusoidal rotations (0.01 Hz to 2
      Hz, peak head velocity of 40 deg/s) in the dark. Vestibular responses were linear
      at 0.5 and 0.05 Hz for peak head velocities between 40 and 80 deg/s. As in other
      species, the gain increased and the phase lead decreased with increasing
      frequencies. The number of fast phases per second increased with peak head
      velocity and with increasing frequencies from 0.01 to 0.5 Hz, with a plateau
      between 0.2 and 0.5 Hz. The HVOR time constant, when measured in response to
      velocity steps, was 7.0 +/- 1.5 s and the latency of the vestibular responses
      averaged 21 +/- 4 ms. Finally, the HVCR was assessed in unrestrained guinea-pigs
      subjected to horizontal sinusoidal rotation in the frequency range of 0.05-2 Hz.
      Exploratory behaviour was prevalent and there were few head stabilization
      episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150045
TI  - The horizontal vestibulo-ocular reflex in the hemilabyrinthectomized guinea-pig.
AB  - The horizontal vestibulo-ocular reflex (HVOR) in the alert guinea-pig elicited by
      sinusoidal rotations and by velocity steps was studied with scleral search coil
      measurement between 3 and 7 days (short term) and between 35 and 160 days (long
      term) after hemilabyrinthectomy. Animals of the short-term group were always
      tested after spontaneous nystagmus in darkness had disappeared. The HVOR gain in
      response to sinusoidal rotations (peak angular velocity: 40 deg/s) in the short
      term group was bilaterally depressed compared to normal animals. The HVOR phase
      showed a shift towards larger phase leads over the whole frequency range tested
      (from 0.05 to 3 Hz). In addition, both the mean number of fast phases per half
      cycle of sinusoidal rotation and the mean amplitude were reduced. HVOR responses
      to velocity steps at a constant acceleration of 300 deg/s2 up to final velocity
      (0 to 100 deg/s) and of 1000 deg/s2 up to final velocity (0 to 300 deg/s) were
      depressed bilaterally and asymmetrically such that the gain for rotation towards
      the intact side greatly exceeded that obtained for rotation towards the lesioned
      side. Finally, the latency of the vestibular responses was increased and the time
      constant reduced for both sides of rotation. The HVOR gain values for sinusoidal
      rotations in the long-term group were lower than normal but higher than in the
      short-term group: they were asymmetric as a result of a greater compensation for
      rotation towards the intact side. Neither the phase lead nor the HVOR latency and
      time constant recovered values close to normal. Finally, the mean number of fast
      phases per half-cycle remained depressed although the mean amplitude recovered.
      These results demonstrate that in the guinea-pig, the dynamic deficits show a
      certain degree of recovery after unilateral labyrinthectomy. However, compared to
      the compensation of the static deficits previously quantified, the rate of
      recovery is much lower. This suggests that different processes may be involved in
      the compensation of the static and dynamic deficits.

PMID- 8150046
TI  - Directional tuning of motion-sensitive cells in the anterior superior temporal
      polysensory area of the macaque.
AB  - An investigation was made into the directional sensitivity of cells in the
      macaque anterior superior temporal polysensory region (STPa) to the motion of
      objects. The cells studied were sensitive to the presence of motion but showed
      little or no selectivity for the form of the stimulus. Directional tuning was not
      continuously distributed about all possible directions. The majority of cells
      were most responsive to motion in a direction within 15 degrees of one of the
      three cartesian axes (up/down, left/right, towards/away). Tuning to direction
      varied in sharpness. For most (34/37) cells the angular change in direction
      required to reduce response to half maximal was between 45 and 70 degrees (for
      3/37 cells it was > 90 degrees). The estimates of the directionality (median Id =
      0.97) of STPa cells was similar to that reported for posterior motion processing
      areas (the middle temporal area, MT, and the medial superior temporal area, MST).
      The tuning for direction (sharpness, distribution and discrimination) of the
      motion-sensitive STPa cells were found to be similar to the tuning for
      perspective view of STPa cells selective for static form of the head and body. On
      average the STPa responses showed a 100- to 300-ms transient burst of activity
      followed by a tonic discharge maintained at approximately 20% of the peak firing
      rate for the duration of stimulation. The responses of motion-sensitive STPa
      cells occurred at an earlier latency (mean 91 ms) than responses of cells
      selective for static form (mean 119 ms), but the time course of responses of the
      two classes of cell were similar in many other respects. The early response
      latency and directional selectivity indicate that motion sensitivity in STPa
      cells derives from the dorsal visual pathway via MT/MST. The similarity of tuning
      for direction and perspective view within STPa may facilitate the integration of
      motion and form processing within this high-level brain area.

PMID- 8150047
TI  - Distribution of neurons expressing substance P receptor messenger RNA in immature
      and adult cat visual cortex.
AB  - We have investigated the expression of messenger RNA (mRNA) encoding substance P
      receptor (SPR) in the visual cortex of adult cats and 17-day-old kittens, using
      in situ hybridization histochemistry with two digoxigenin-labeled
      oligodeoxynucleotides complementary to the SPR mRNA. In the adult cortex, a
      subset of large pyramidal neurons of layer V and layer III is heavily labeled.
      Other, mainly pyramidal neurons in layers II, III and V are less intensely
      labeled, but most neurons in these layers appear unlabeled. Neurons in layer IV
      and VI, and in the white matter do not show hybridization signals above
      background levels. In the 17-day-old kitten, SPR mRNA-expressing cells are
      confined to layer V and to the upper white matter (subplate zone), whereas
      supragranular neurons do not yet contain SPR mRNA. A few neurons in layer VI
      display moderate labeling. Astrocytes, identified with anti-glial fibrillary acid
      protein antibodies, did not express detectable levels of SPR mRNA in both adult
      and kitten visual cortex. These results indicate that SPR mRNA expression is
      transient in neurons of the white matter, and is developmentally regulated in
      supragranular layers. In addition, the localization of SPR mRNA in a subset of
      pyramidal cells suggests that substance P modulates the excitability of certain
      projection neurons which are the origin of extrinsic connections.

PMID- 8150048
TI  - Fictive locomotion in the adult thalamic rat.
AB  - In immobilized adult thalamic rats, electrical stimulation of sites within the
      lateral hypothalamic area (LHA) or the mesencephalic locomotor region (MLR) were
      found to elicit fictive locomotor patterns in hindlimb muscle nerves. Significant
      differences were found between several characteristics (average cycle period,
      locomotor episode duration, intralimb and interlimb coordination patterns) of the
      LHA-induced and MLR-induced fictive locomotor activities. These findings support
      the hypothesis that LHA and MLR play different functional roles during
      locomotion.

PMID- 8150049
TI  - Goldfish ganglion cells with unusual receptive field properties.
AB  - Goldfish retinal ganglion cells with unusual response properties are described.
      Each cell was classified as either Y-like or W-like, based upon its responses to
      sinusoidally modulated contrast-reversal gratings presented at various positions
      across the cell's receptive field. The unusual responses of the cells (which
      distinguish them from typical Y-like and W-like cells) occurred when sinusoidal
      gratings were drifted across the receptive field at a constant temporal rate.
      These cells responded at double the stimulus temporal rate to low-spatial
      frequency gratings; a Fourier decomposition of the response revealed a large
      second harmonic component. However, to high-spatial-frequency stimuli, the
      response modulated at the temporal frequency of the stimulus; the Fourier
      fundamental component dominated the response. To examine the underlying receptive
      field mechanisms of these cells, each cell's response was analyzed using several
      different response measures. The results suggest that the receptive field
      properties of these unusual cells differ from the typical center/surround
      organization and confirm recent findings that the receptive fields of goldfish
      ganglion cells consist of inhomogeneities and subareas.

PMID- 8150050
TI  - Cerebral response to pyramidal tract stimulation in wood rats and its relation to
      laboratory rats.
AB  - The cerebral response evoked by stimulation of the bulbar pyramidal tract in wood
      rats, like that of laboratory rats, consisted of a small alpha wave, almost
      obscured by a very large, superimposed r wave. The alpha wave behaved like a
      purely antidromic response, whereas the r wave behaved like a postsynaptic
      response, including a marked variability in amplitude on repeated trials. The
      contralateral forepaw and hindpaw motor sites mapped onto the somatic sensory
      foci for these two paws; further examination showed that the somatic sensory and
      motor representations were largely superimposed. An incipient sagittal fissure
      1.5 mm lateral to the midline marked the boundary between limbic and neocortex.
      Because of their structural similarities and their differences in somatic sensory
      and motor organization, wood rats and laboratory rats are prime subjects for
      comparative study of the role of amalgamated and separate sensory and motor
      cortices in regulating movement and behavior.

PMID- 8150051
TI  - A possible visual pathway to the cat caudate nucleus involving the pulvinar.
AB  - Electrical stimulation of the thalamic nucleus pulvinar was found to influence
      unit activity in the feline caudate nucleus. Twenty-six (18.3%) units were
      encountered, in this subcortical region of the brain, that responded to
      activation of the pulvinar input in anesthetized cats and 41 (54%) in awake
      animals. In the two types of experiments, stimulation of the pulvinar induced
      mainly an initial excitatory reaction (81% and 78% of responsive cells,
      respectively). A latency analysis indicated that the majority of responses
      occurred at a long latency, while 9 (34.6%) cells in anesthetized cats and 5
      (12%) in awake animals were excited at a short latency. The short latency is
      compatible with the involvement of a monosynaptic pathway between the pulvinar
      and the caudate nucleus. Units that responded to thalamic stimulation were found
      predominantly in the posterior regions of the caudate nucleus. These results
      confirm previous neuroanatomical findings of a direct projection from the
      pulvinar to the feline caudate nucleus. In awake animals, neurons activated by
      pulvinar stimulation were also tested, using visual stimuli of various
      orientations. Out of 41 units, 63% were classified as having "visual responses".
      Of these, 5 cells were found to respond selectively to a particular orientation
      of the visual stimulus. Three of these were excited at a short latency by
      pulvinar stimulation. The possible involvement of a direct pathway from the
      pulvinar to the caudate nucleus in the processing of visual information is
      discussed.

PMID- 8150052
TI  - Membrane potential oscillations in CA1 hippocampal pyramidal neurons in vitro:
      intrinsic rhythms and fluctuations entrained by sinusoidal injected current.
AB  - The mechanisms mediating intrinsic and entrained CA1 pyramidal neuron rhythmic
      membrane potential oscillations were investigated in rat hippocampal slices.
      Intrinsic oscillations (6-14 Hz, < 10 mV) were evoked by long duration (2 s),
      depolarizing current pulses in 42% of the cells. Oscillations were also evoked by
      imposing sinusoidal transmembrane currents at 2, 7, and 14 Hz, adjusted at 7 Hz
      to imitate the synaptically mediated in vivo "intracellular theta". Slow all-or
      none events (40 mV, 55 ms)--reminiscent of the rhythmic, high threshold slow
      spikes observed in vivo--were evoked and entrained by the sine wave current
      cycles with large, imposed depolarization in 35% of the cells. Intrinsic
      oscillations were insensitive to Ca(2+)-free, Co2+ (2 mM) and Mn2+ (2 mM)
      solutions, but were blocked by tetrodotoxin (TTX; 5 microM), illustrating that
      they were Na(+)-mediated. Tetraethylammonium (TEA; 15 mM) unmasked slow all-or
      none events (40-50 mV, 20-55 ms) and plateau potentials (40-60 mV, 100-700 ms).
      Plateaus were Co2+ and Mn2+ resistant and were abolished by TTX, hence suggesting
      that the underlying persistent conductance was Na(+)-mediated. Plateaus were
      entrained one-to-one at all sinusoidal current frequencies in Ca(2+)-free, TEA +
      Co2+, or TEA + Mn2+ solutions. However, the high threshold Ca2+ spikes uncovered
      in TEA + TTX could only follow sinusoidal currents of less than 7 Hz. In
      conclusion, the high threshold Ca2+ and persistent Na+ conductances coexist in
      CA1 pyramidal cells. The persistent Na+ conductance mediated the intrinsic
      oscillations, and fluctuated at all the sine wave current frequencies used. The
      more sluggish high-threshold Ca2+ conductance exclusively oscillated at
      frequencies of less than 7 Hz and did not support the intrinsic rhythm.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8150053
TI  - Optokinetic-vestibular interaction in patients with increased gain of the
      vestibulo-ocular reflex.
AB  - We studied optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and
      visual-vestibular interaction in five patients with markedly elevated vestibulo
      ocular reflex (VOR) gain due to cerebellar atrophy. All had impaired smooth
      pursuit, decreased initial slow phase velocity of OKN, and impaired ability to
      suppress the VOR with real or imagined targets. OKN slow phase velocity gradually
      built up over 25-45 s, reaching normal values for low stimulus velocities (< or =
      30 deg/s). Initial velocity of OKAN was increased, but the rate of decay of OKAN
      was normal. These findings can be explained by models that include separate
      velocity storage and variable gain elements shared by the vestibular and
      optokinetic systems.

PMID- 8150054
TI  - Selective impairment of express saccade generation in patients with
      schizophrenia.
AB  - When a temporal gap is introduced between the offset of a central fixation point
      and the onset of a peripheral saccadic target, normal subjects generate an
      increased number of short latency (90-150 ms) saccades, termed express saccades,
      and the profile of express saccade frequency across different gap sizes for any
      individual subject, even if untrained in the task, shows a high test-retest
      reliability. In patients with schizophrenia, the generation of express saccades
      was also normal for gap sizes of 200-300 ms or in an overlap task (gap = 0 ms).
      However, for temporal gaps of 50-150 ms, the generation of express saccades was
      significantly impaired in the schizophrenic subjects. This selective deficit
      appeared to be independent of the patients' neuroleptic medication status and did
      not correlate with the severity of schizophrenic symptoms. It is postulated that
      the successful execution of an express saccade requires that the cognitive
      operations of disengagement of visual attention and selection of the appropriate
      motor command to generate a saccade both be commenced or completed during the
      temporal gap between fixation offset and peripheral target onset. Our results
      suggest that, in schizophrenia, there is an impairment in the
      cortical/subcortical neural network that generates express saccades and controls
      these cognitive operations. Potential sites for such dysfunction in schizophrenia
      include the parietal cortex and the GABA-ergic function of the superior
      colliculus.

PMID- 8150055
TI  - Cyclovergence: a comparison of objective and psychophysical measurements.
AB  - Several psychophysical procedures have been used to measure cyclovergence but
      none has been adequately validated with respect to an objective measure. Scleral
      search coils were used to measure cyclovergence induced by dichoptic textured
      patterns which cyclorotated in antiphase through 6 degrees at frequencies between
      0.05 and 2 Hz. In one psychophysical procedure subjects nulled the apparent
      oscillatory motion of radial nonius lines superimposed on a small black disc at
      the center of a large cyclorotating display. In the second, subjects nulled the
      apparent inclination in depth of a vertical line displayed in the same way. The
      amplitude of cyclovergence measured objectively and the magnitude of oscillation
      of the nonius lines were similar at low stimulus frequencies. At higher
      frequencies of cyclorotation, both amplitudes declined but the nonius amplitude
      exceeded that of cyclovergence. The apparent inclination of the vertical test
      line, as indicated by the nulling procedure, also declined with increasing
      frequency of cyclorotation, but not at the same rate. At low frequencies, the
      apparent inclination of the test line was greater than that corresponding to the
      cyclodisparity induced into the line and almost as great as that corresponding to
      the relative disparity between the oscillating pattern and the line. The
      implications of these results for measuring cyclovergence and for an
      understanding of stimuli driving cyclovergence and perceived inclination in depth
      are discussed.

PMID- 8150056
TI  - The time of secondary saccades to primary targets.
AB  - When a first saccade is made in response to a single, suddenly appearing stimulus
      it often misses the target. The retinal error may be very large, in particular in
      those cases where the subject anticipates the target location and initiates a
      saccade to a wrong position. We have analyzed the time of the occurrence of the
      secondary saccades by which the subject corrects these errors. Using the gap task
      with random target locations we found that large errors after anticipatory
      saccades--especially those after direction errors--can be corrected very fast.
      The latencies of these corrective saccades (being measured from target onset, not
      from the end of the primary saccade) form bimodal distributions with a first peak
      at 100 ms. It is therefore concluded that large errors can be corrected by
      express secondary saccades.

PMID- 8150057
TI  - Control of torque direction by spinal pathways at the cat ankle joint.
AB  - To study the biomechanics of the calcaneal tendon's complex insertion onto the
      calcaneus, we measured torque-time trajectories exerted by the triceps surae and
      tibialis anterior muscles in eight unanesthetized decerebrate cats using a multi
      axis force-moment sensor placed at the ankle joint. The ankle was constrained to
      an angle of 110 degrees plantarflexion. Muscles were activated using crossed
      extension (XER), flexion (FWR), and caudal cutaneous sural nerve (SNR) reflexes.
      Torque contributions of other muscles activated by these reflexes were eliminated
      by denervation or tenotomy. In two animals, miniature pressure transducers were
      implanted among tendon fibers from the lateral gastrocnemius (LG) muscle that
      insert straight into the calcaneus or among tendon fibers from the medial
      gastrocnemius (MG) that cross over and insert on the lateral aspect of calcaneus.
      Reflexively evoked torques had the following directions: FWR, dorsiflexion and
      adduction; SNR, plantarflexion and abduction; and XER, plantarflexion and modest
      abduction or adduction. The proportion of abduction torque to plantarflexion
      torque was always greater for SNR than XER; this difference was about 50% of the
      magnitude of abduction torque generated by tetanic stimulation of the peronei.
      During SNR, pressures were higher in regions of the calcaneal tendon originating
      from MG than regions originating from LG. Similarly, pressures within the MG
      portion of the calcaneal tendon were higher during SNR than during XER, although
      these two reflexes produced matched ankle plantarflexion forces. Selective
      tenotomies and electromyographic recordings further demonstrated that MG
      generated most of the torque in response to SNR, while soleus, LG, and MG all
      generated torques in response to XER.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150058
TI  - Respiratory illness and mortality in England and Wales. A study of the
      relationships between weekly data for the incidence of respiratory disease
      presenting to general practitioners, and registered deaths.
AB  - The possible relationship between the incidence of respiratory diseases as
      reported to general practitioners and numbers of registered deaths in England and
      Wales has been examined. Morbidity data from sentinel practices for the period
      1986-1990 (population covered increased from 220,000 to 470,000) were used to
      calculate weekly rates of aggregated respiratory disease for persons of all ages
      and for elderly persons (aged 65 years and over). The elderly respiratory disease
      rates and numbers of deaths were aggregated into 4-week periods; secular and
      seasonal trends were removed from each series and the two sets of residuals were
      examined graphically and cross correlation coefficients calculated. There was a
      very strong positive association between the respiratory disease rate and number
      of deaths in the same 4-week period and there was also a significant but less
      pronounced association between respiratory disease in one 4-week period and
      deaths in the next. After prior separation of weeks according to temperature into
      four bands, weekly rates for respiratory disease were also strongly associated
      with the number of weekly deaths for each temperature band. The synchronisation
      of peaks and troughs in the two series throughout the year supports the
      hypothesis that a cause and effect relationship exists between respiratory
      disease in the elderly and number of deaths. Other climatic and meteorological
      variables besides temperature may play a part in determining the spread of a
      respiratory disease. There is a for further research to identify the micro
      organisms responsible for acute respiratory infections in the elderly.

PMID- 8150059
TI  - Predictors of mortality in very old subjects aged 80 years or over.
AB  - We studied 318 subjects aged 80 years of over included in the Cardiovascular
      Study in the Elderly (CASTEL). Some well known risk factors (left ventricular
      hypertrophy, glucose intolerance, cholesterol, ApoB/ApoA ratio, triglycerides,
      proteinuria, cigarette smoking, and ECG abnormalities), whose importance in
      cardiovascular risk is definitely accepted for young adults, were very poor
      predictors of mortality in our survey. On the contrary, FEV1 reduction and blood
      uric acid were strong predictors.

PMID- 8150060
TI  - The descriptive epidemiology of pharyngeal cancer in Scotland.
AB  - There have been recent reports of substantial increases occurring in the
      incidence of and/or mortality from tongue and mouth cancers in several countries.
      In this paper using data from Scotland (1960-89) we report on time trends in
      pharyngeal cancer. Similar increases in rates are evident for cancers of the
      oropharynx and hypopharynx while there has been little change in the occurrence
      of nasopharyngeal cancer (which has distinct aetiological factors). It therefore
      seems that reported changes in the incidence of and mortality from oral cancer
      may be real, and in Scotland, this is most probably due to changes in alcohol
      consumption.

PMID- 8150061
TI  - A local education campaign on early diagnosis of malignant melanoma.
AB  - The growing incidence of all kinds of skin cancer is a worldwide phenomenon
      observed in the last decades. Malignant melanoma is of special concern because of
      its high death rate when in an advanced stage, poor therapeutic response and fast
      growing incidence. Malignant melanoma is primarily located on the skin and
      therefore well suited for early cancer detection. The "Deutsche Dermatologische
      Gesellschaft" carried out a highly successful information campaign in Germany.
      Under this roof we organised different campaigns. Following considerable success
      in a campaign in 1989, a total of 1467 patients were examined and advised in the
      course of a local initiative (Education Campaign "Black cancer") in the city of
      Bochum (approximately 400,000 inhabitants) in the summer of 1991. In addition to
      full body examinations, important data were collected concerning the degree of
      knowledge about skin cancer, epidemiology, and the risk of skin cancer in
      general. As a result of the clinical examinations, 73 patients with strongly
      suspected skin cancer have been treated. Within this group, 14 malignant
      melanomas (1.0%) as well as 34 basal cell carcinomas (1.9%) were diagnosed. These
      numbers highly exceed the assumed risk incidence of skin cancer in Germany. Even
      on the assumption that the population was selective it is to be feared that a
      high number of individuals with skin cancer remain undetected and untreated. The
      majority of persons seeking advice had been motivated by the local media. The
      response and results of this local campaign indicate that further preventive
      measures for the general population in Europe are conceivable, meaningful and
      urgently needed.

PMID- 8150062
TI  - Moderate maternal drinking and outcome of pregnancy.
AB  - The adverse effect of light or moderate maternal drinking during pregnancy on the
      well being of the newborn has been investigated. The study group included 2145
      live births in the obstetric units of 11 Italian cities between February 1989 and
      July 1990. A detailed life style questionnaire was administered to the mothers.
      Information on the newborn was collected from clinical records as well as from a
      clinical examination. Both univariate and multivariate analyses were suggestive
      of a decrease in mean birth weight associated with maternal drinking pregnancy,
      especially in women who also smoked during pregnancy. This effect was higher in
      male newborns. The occurrence of low birth weight (< 2500 g.) was more frequent
      in women drinking during pregnancy in both smokers and non-smokers (for this
      latter group an effect is suggested only for a daily consumption of more than 10
      grams of absolute alcohol). Maternal alcohol drinking of more than 20 grams of
      absolute alcohol per day also increased the risk of preterm delivery (OR = 2.35;
      95% CI: .98-5.59). Finally, an increase in the rate of early jaundice was found,
      also associated with maternal drinking (OR = 3.30; 95% CI: 1.03-10.54).

PMID- 8150063
TI  - The epidemiology of three serious cardiac defects. A joint study between five
      centres.
AB  - The paper reports a joint study made by five member programs of the International
      Clearinghouse for Birth Defects Monitoring Systems. Three specific heart
      malformations were studied, hypoplastic left heart syndrome (HLHS), transposition
      of the great vessels (TGV), tetralogy of Fallot, and some epidemiological
      characteristics were analyzed. The prevalence at birth was estimated to be 2.0,
      2.9, and 2.2 per 10,000 births, respectively. No time trend in the prevalence at
      birth was observed for any one of the three malformations in the total study
      population. When only isolated defects were considered (infants without major non
      cardiac malformations), all three cardiac anomalies showed an increased rate in
      infants with low birth weight, short gestational duration and probably twinning.
      A preponderance for males was observed for each defect but was strongest among
      infants with tetralogy of Fallot (sex ratio 2.5 for Fallot, 1.4 to 1.5 for the
      other conditions). There were also differences between the three cardiac defects
      with respect to percentage of low birth weight, preterm births, and rate and type
      of associated extracardiac malformations. This paper stresses the advantage of
      pooling data from different registries in studies of uncommon specific
      malformations and infrequent characteristics.

PMID- 8150064
TI  - Tetanus in Switzerland 1980-1989.
AB  - Tetanus cases that occurred in Switzerland between 1980 and 1989 have been
      reviewed with the help of three data surveillance systems: a) morbidity data from
      the Federal Office of Public Health (FOPH), b) mortality data from the Swiss
      Federal Statistical Office (SFSO), and c) data from the Association of Swiss
      Hospitals and Clinics (VESKA), completed by a written enquiry to clinics which
      did not (or only partly) participate in the VESKA system during the study period.
      For every case, a questionnaire was sent to the clinic to verify the diagnosis
      and to obtain additional information on the circumstances of occurrence. Ninety
      one cases were identified. This corresponds to a yearly incidence of 1.93 per
      million population between 1980-84 and 0.88 for the 1985-89 period (p < 0.01).
      Eighty-one percent of the cases were older than 50 years of age and women were
      significantly more frequently affected than men. None of the cases identified had
      a documented primary immunization series. Data available at the FOPH and SFSO
      level have been compared to data obtained through the VESKA system using the
      Chandra Sekhar and Deming method. It is estimated that 134 tetanus cases (95% CI:
      91-197) have occurred in Switzerland between 1980 and 1989, together with 28
      deaths (95% CI: 27-31). Based on these estimates, FOPH appears to detect only 6
      13% of tetanus cases occurring in Switzerland. By contrast, SFSO had fairly
      consistent data for 81-100% of tetanus associated deaths. The low rate of tetanus
      reported by physicians necessitates a sustained effort to increase the
      understanding of epidemiological surveillance by Swiss practitioners.

PMID- 8150065
TI  - Risk factors for acute parenterally transmitted viral hepatitis: a 20-year study.
AB  - In order to verify the relative role of each single risk factor during a long
      period of observation, and to compare the frequency of risk factors in
      parenterally and non-parenterally transmitted acute viral hepatitis, we studied
      1,251 patients admitted to our Department from 1971 to 1991. Acute hepatitis A
      cases were considered non-parenterally transmitted, whereas B, C, NANB and Delta
      hepatitis were grouped together as parenterally transmitted. The two groups were
      compared for age, sex and the following risk factors: surgical procedures,
      transfusion, dental procedures, intravenous drug addiction, infected partner,
      infected relative and hospital admission. There were 243 non-parenterally
      transmitted and 1,008 parenterally transmitted cases. In univariate analysis,
      mean age in the two groups was 20 and 37 years (p = 0.000001) for non
      parenterally and parenterally transmitted cases respectively; mean ages of
      patients with different parenterally transmitted hepatitis (B, NANB, C, Delta)
      did not differ significantly (p = 0.35). The following risk factors were
      significantly more frequent in the parenterally transmitted hepatitis group:
      surgical procedure (odds ratio = 8.04, 95% confidence intervals: 3.75, 20.51),
      transfusion (OR = 18.79, 95% CI: 5.03, 157.72), dental procedures (OR = 2.19, 95%
      CI: 1.2, 4.06), drug addiction (OR: 11.02, 95% CI: 4.15, 41.34), and infected
      partner (OR = 17.61, CI: 3.02, 708.65). However, logistic regression showed the
      following factors as being significant: age (p = 0.00001), transfusion (OR =
      3.35, 95% CI: 1.61, 6.94), dental procedures (OR = 1.61, 95% CI: 1.18, 2.2), drug
      addiction (OR = 4.88, 95% CI: 2.94, 8.1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150066
TI  - Risk factors for severe disease due to Toxoplasma gondii in HIV-positive
      patients.
AB  - The objective of this study was to assess the risk of toxoplasmosis in HIV
      positive subjects as a basis for primary prophylaxis. A retrospective chart
      review of 400 consecutive patients was carried out and clinical and laboratory
      markers at first presentation and follow-up data on the occurrence of
      toxoplasmosis were recorded. Independent variables were identified, laboratory
      parameters were stratified, and estimates for the risk of toxoplasmosis and the
      impact of different variables on its occurrence were made using conventional
      statistical methods. An increased risk of toxoplasmosis was strongly associated
      with a positive Toxoplasma gondii IgG EIA in conjunction with a CD4+ cell cont
      below 0.15/nl (the estimated risk of toxoplasmosis was 20% and 35% after 12 and
      24 months, respectively) or a history of one or more opportunistic infections
      (the estimated risk was 12% and 30% after 12 and 24 months, respectively).
      Toxoplasma gondii-seropositive patients with CD4+ cell counts below 0.15/nl and
      those with antecedent opportunistic infections are most likely to develop
      toxoplasmosis and thus might benefit from primary prophylaxis. The risk of
      disease probably outweighs the risk of medication in these subjects. Prospective
      clinical trials are needed to define the optimal choice of drugs.

PMID- 8150067
TI  - An emerging opportunistic infection in HIV patients: a retrospective analysis of
      11 cases of pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis usually occurs in patients with severe
      granulocytopenia or defects of cell-mediated immunity secondary to cytotoxic
      chemotherapy or high-dose corticosteroids, but it is an unusual opportunistic
      infection in patients with AIDS. Eleven cases of Aspergillus pulmonary disease
      were diagnosed in HIV-infected patients from January 1985 to December 1992, in
      the Department of Infectious Diseases of the Catholic University. Four patients
      had invasive pulmonary aspergillosis, six probable pulmonary invasive
      aspergillosis and one allergic bronchopulmonary aspergillosis. Fiberoptic
      bronchoscopy with bronchoalveolar lavage was confirmed to be an useful tool for
      the diagnosis of pulmonary aspergillosis in AIDS patients. The response of
      aspergillosis to therapy, either amphotericin B or itraconazole, has usually been
      poor. It is possible to speculate that the longer survival of AIDS patients and
      the latter development of other functional immunological abnormalities related to
      HIV infection may allow the appearance of opportunistic infection, such as
      pulmonary aspergillosis, different from those more often observed.

PMID- 8150068
TI  - Identification of Rickettsia prowazekii using the polymerase chain reaction.
AB  - Polymerase chain reaction (PCR) was used to identify Rickettsia prowazekii, the
      etiologic agent of epidemic typhus. For the PCR, Thermus thermophilus
      thermostable DNA polymerase was applied with buffer containing a relatively low
      Mg2+ concentration (1.5-2 mM with dNTP's at 250 microM each). A primer pair used
      to amplify a 448-base-pair (bp) fragment of R. prowazekii genome was synthesized
      on the basis of the DNA sequence of gene rpa14/16, coding for a precursor of the
      mature polypeptides of molecular weight (Mr) 14,000 and/or 16,000 (16kD) from R.
      prowazekii strain E. For determining the specificity of the primer pair, purified
      genomic DNAs of 16 rickettsial and 10 other bacterial strains were used.

PMID- 8150069
TI  - Molecular epidemiology of two genes encoding 3-N-aminoglycoside
      acetyltransferases AAC(3)I and AAC(3)II among gram-negative bacteria from a
      Spanish hospital.
AB  - The molecular epidemiology of the aacC1 and aacC2 genes, encoding 3-N
      aminoglycoside acetyltransferases AAC(3)I and AAC(3)II, respectively, was studied
      by DNA-DNA hybridization. The sample included 315 gentamicin-resistant Gram
      negative bacilli collected over a six-month period from patients attending a
      Spanish Hospital. The aminoglycoside resistance phenotype of these strains was
      also determined. The aacC1 probe hybridized with 39 strains, the aacC2 probe with
      146 strains and both probes hybridized with 26 strains. The aacC1 gene was most
      frequently detected in Pseudomonas aeruginosa whereas the aacC2 gene was most
      frequently detected in enterobacteria and Acinetobacter spp. Strains harbouring
      aacC genes were isolated from both in- and outpatients with different infectious
      diseases, mainly urinary tract infections. As inferred from the results of
      Southern hybridization, both genes showed a wide horizontal dispersion among
      plasmids and bacteria.

PMID- 8150070
TI  - In vitro activity of ceftriaxone and other cephalosporins against 602 clinical
      isolates of staphylococci from geographically diverse medical centers.
AB  - The in vitro activity of ceftriaxone and six additional antimicrobial agents
      (ceftizoxime, cefoperazone, cefuroxime, fleroxacin, ciprofloxacin, and
      trimethoprim/sulfamethoxazole) was assessed or 602 recent clinical isolates of
      staphylococci from six geographically distinct medical centers in North America.
      All seven antimicrobial agents were active (90-100% of strains susceptible)
      against oxacillin-susceptible (OS) strains of Staphylococcus aureus (OSSA) and
      coagulase-negative staphylococci (OSCNS) but had limited activity against
      oxacillin resistant (OR) staphylococci. Our assessment of the in vitro
      antistaphylococcal activity of ceftriaxone against contemporary isolates of
      Staphylococcus aureus and coagulase-negative staphylococci indicates that the
      activity versus OS staphylococci has not changed over the past decade despite
      widespread use of the drug. It appears that these agents will continue to be
      useful for empiric therapy in those centers in which OR strains are uncommon.

PMID- 8150071
TI  - Declining prevalence of HIV infection among injecting drug users entering drug
      treatment in Italy: 1990-1991.
AB  - Two surveys were conducted in 1990 and 1991 in order to estimate the prevalence
      of HIV infection among injecting drug users attending drug treatment centers
      throughout Italy. Among the 35,073 IDUs attending these facilities in 1990, 32.1%
      were HIV-positive. In 1991, 29.7% of 41,794 IDUs were HIV-positive. HIV
      prevalence was higher among prior attendees compared to new entrants (38.0% vs.
      20.5% in 1990, and 35.8% vs. 16.6% in 1991); prevalence was also higher among
      females. These findings suggest that HIV prevalence among Italian drug users is
      slowly declining.

PMID- 8150072
TI  - Influenza epidemic among a community of elderly people in spite of vaccination.
AB  - An outbreak of influenza occurred in a nursing home of 81 vaccinated elderly
      people. The clinical attack rate was 73%. The responsibility of an A/H3N2 strain
      was proved in 12 patients and 2 staff members of the 15 investigated persons. The
      vaccine was effective in reducing mortality but not morbidity. An antigenic drift
      between the wild and the vaccine strains was involved in the inefficiency of the
      vaccination.

PMID- 8150073
TI  - A case of infant botulism associated with honey feeding in Italy.
AB  - A case of infant botulism in a 9 week-old female is described. A strain of C.
      botulinum type B was isolated from the feces of the baby. The epidemiologic study
      detected in a sample of home canned honey Clostridium botulinum spores of the
      same serotype that was isolated from the patient. The honey had been used only to
      sweeten the pacifier of the baby. This is the first case of infant botulism in
      Europe linked conclusively to honey.

PMID- 8150074
TI  - Maternal sauna and hyperthermia during pregnancy and cardiovascular and other
      malformations in offspring.

PMID- 8150075
TI  - Expression of a bovine vesicular monoamine transporter in COS cells.
AB  - Catecholamines are accumulated in vesicles by a proton gradient-dependent
      transport, which has mostly been studied in bovine chromaffin granules. The full
      sequence of a cDNA encoding a vesicular transporter from bovine chromaffin cells,
      bVMAT2, was recently reported. We now present an analysis of bVMAT2, expressed in
      transfected COS cells. Comparing the binding of a labelled ligand, [3H]TBZOH, and
      the rate of uptake, we find a much lower molecular turnover number than in
      chromaffin granules, probably indicating that a majority of expressed
      transporters are correctly folded and possess the ligand binding site but cannot
      actively transport monoamines because they are located in compartments which do
      not possess a proton gradient. The substrate specificity of uptake and its
      pharmacological sensitivity to various inhibitors closely resemble those
      previously observed in chromaffin granules. These results suggest that VMAT2 is
      the major transporter in bovine adrenal glands, and raise the question of the
      significance of the second related transporter, VMAT1, which is also expressed in
      this tissue.

PMID- 8150076
TI  - The accessibility of peptides bound to the mouse MHC class II molecule IEd
      studied by fluorescence.
AB  - The accessibility of fluorescently labeled (antigenic) peptides bound to the
      detergent-solubilized mouse MHC class II protein IEd has been studied by
      fluorescence techniques. Based on the efficiency of fluorescence quenching by the
      aqueous quenchers iodide and TEMPOL, different degrees of accessibility of the
      peptide-attached fluorescein moiety are distinguished in the IEd-bound state,
      which depend on the nature of the peptide and on the site of attachment. These
      different extents of sequestration from the aqueous phase are reflected in the
      fluorescence properties of the corresponding NBD-labeled peptides bound to IEd.
      The results provide information on the topology of class II bound peptides.

PMID- 8150077
TI  - Cloning and expression of the bovine sodium- and chloride-dependent noradrenaline
      transporter.
AB  - A cDNA encoding a functional bovine, tricyclic antidepressant-sensitive
      noradrenaline transporter has been identified by screening a lambda gt11 cDNA
      library of the bovine adrenal medulla using the cDNA of the human noradrenaline
      transporter [1991, Nature 350, 350-354]. The sequence predicts a protein of 615
      amino acids (M(r) 68,900). The bovine transporter shares 93% amino acid identity
      with the human sequence, but displays two more consensus sites for
      phosphorylation by protein kinase C. Transient expression of the transporter in
      COS-7 cells resulted in a sodium- and chloride-dependent uptake of noradrenaline
      with a pharmacology typical for a neuronal noradrenaline transporter.

PMID- 8150078
TI  - Precise expression of the cAMP receptor gene, CAR1, during transition from growth
      to differentiation in Dictyostelium discoideum.
AB  - The gene expressions associated with the switch-over from cell proliferation of
      Dictyostelium discoideum to differentiation have been analyzed using temperature
      shift and differential plaque hybridization methods. Quit1 was cloned as a
      specifically expressed gene when cells were starved just before the PS point
      (putative shift point from growth to differentiation). The coding region of the
      Quit1 gene is identical to that of the cAMP receptor 1 (CAR1) gene, which is
      essential for development. Quit1 mRNA was specifically expressed just after
      starvation of cells at around the PS point, thus indicating the importance of
      CAR1 for cellular differentiation as well as the actual existence of the PS
      point.

PMID- 8150079
TI  - Enhanced intracellular delivery of doxorubicin by scavenger receptor-mediated
      endocytosis for preferential killing of histiocytic lymphoma cells in culture.
AB  - A conjugate of the antineoplastic drug doxorubicin (DXR) with maleylated bovine
      serum albumin (MBSA) was taken up by a human histiocytic lymphoma cell line
      (U937) through the high efficiency process of scavenger receptor-mediated
      endocytosis resulting in a sixfold higher intracellular concentration of the drug
      compared to that obtained when the free drug was administered. Compared to the
      free drug, the drug conjugate showed significantly higher cytotoxicity towards
      U937 cells presumably because of intracellular availability of a
      pharmacologically active form of the drug. The intracellular product released
      after lysosomal degradation of the drug conjugate was chromatographically
      identical to free DXR. These findings merit serious consideration in the
      development of new chemotherapeutic agents for the treatment of histiocytic
      malignancies.

PMID- 8150080
TI  - Expression of the catalytic domain of cyclic GMP-dependent protein kinase in a
      baculovirus system.
AB  - The Type I cGMP-dependent protein kinase catalytic domain (residues 336-671 from
      the I alpha isoform) has been expressed as a cGMP independent kinase in a
      baculovirus system. Using peptide substrates, the protein retains similar
      substrate specificity as the native holoenzyme. The recombinant catalytic domain
      catalyzes the phosphorylation of histone, but does not display the inhibition
      using non-substrate histones which has been described for the holoenzyme. The
      catalytic domain is an active kinase in mammalian cells also since vascular
      smooth muscle cells transfected with the cDNA encoding the catalytic domain
      display altered morphology. The catalytic domain of G-kinase may be a useful tool
      for delineating the role of cGMP-mediated protein phosphorylation in cell
      systems.

PMID- 8150081
TI  - The intrinsic 22 kDa protein is a chlorophyll-binding subunit of photosystem II.
AB  - The intrinsic 22 kDa polypeptide associated with photosystem II (psbS protein)
      was found to be able to bind chlorophyll. Extraction of isolated photosystem II
      membranes with octyl-thioglucopyranoside, followed by repetitive electrophoresis
      under partially denaturing conditions gave only one green band. It contained both
      chlorophyll a and chlorophyll b, exhibited an absorption maximum at 674 nm and a
      77 K fluorescence peak at 675 nm. The chlorophyll-protein band contained a single
      polypeptide of 22 kDa. Based on these results and on previous protein sequence
      comparisons, it is suggested that the psbS protein is a chlorophyll a/b binding
      polypeptide and should thus be denoted CP22.

PMID- 8150082
TI  - Transforming growth factor beta mediates increase of mature transmembrane amyloid
      precursor protein in microglial cells.
AB  - By using the immortalized microglial cell line BV-2, we show that the high
      expression of the beta A4 amyloid precursor protein (APP), its biogenesis and
      metabolism is modulated by TGF beta, a cytokine with immunosuppressive activity,
      and by the microglia-stimulating agent LPS. TGF beta induces accumulation of
      cellular mature APP, the putative precursor of the amyloid subunit of Alzheimer's
      disease. LPS leads to an increase in cellular immature, non-amyloidogenic APP and
      secretion of also non-amyloidogenic APP fragments. We also demonstrate a
      functional involvement of ECM molecules in the regulation of microglial APP
      expression at mRNA and protein level by TGF beta and LPS.

PMID- 8150083
TI  - Transcription factor GATA-1-multiprotein complexes and chicken erythroid
      development.
AB  - The chicken erythrocyte transcription factor, GATA-1, is associated with several
      non-DNA binding proteins. We show that GATA-1 multiprotein complexes exist in
      primitive and definitive erythrocytes. These complexes bind to GATA motifs of the
      rho-globin promoter and histone H5 enhancer with high affinity, and to the
      chicken beta-globin promoter specialized TATA element and enhancer GATA with low
      affinity. The low affinity beta-globin TATA element would allow basal
      transcription factors to displace the GATA-1 multiprotein complex. Further, our
      results suggest that rho-globin promoter's low affinity Sp1 binding site and
      reduced levels of Sp1 in definitive cells prevent its expression in these cells.

PMID- 8150084
TI  - Cloning of cDNA for granzyme-like protein III, a novel serine proteinase from rat
      duodenum.
AB  - We previously reported cloning of cDNAs which encode two granzyme-like serine
      proteinases (GLP I and GLP II) from rat duodenum. In this paper we present the
      cDNA sequence for a novel member of the granzyme-like protein family from rat
      duodenum, GLP III. The amino acid sequence deduced from the cDNA consists of 248
      residues and shows 88.2% identity to GLP I and 50.6% identity to GLP II.
      Comparison of the amino acid sequence of GLP III with sequences of related
      proteinases reveals the location of the catalytic amino acid triad and enables
      the prediction of the substrate specificity. Despite close similarity to GLP I,
      GLP III is expected to demonstrate different substrate specificity due to a
      substitution of the Arg residue by Glu at the critical position. Northern blot
      analysis demonstrates that the GLP III transcript is present only in duodenum.

PMID- 8150085
TI  - Gallinacins: cysteine-rich antimicrobial peptides of chicken leukocytes.
AB  - We purified three homologous antimicrobial peptides ('gallinacins') from chicken
      leukocytes, examined their antimicrobial activity in vitro, and established their
      primary sequences by a combination of gas phase microsequencing and on-line LC
      ESI-MS analysis of endo- and exoprotease peptide digests. The peptides contained
      36-39 amino acid residues, were relatively cationic due to their numerous lysine
      and arginine residues, and each contained 3 intramolecular cystine disulfide
      bonds. Gallinacins showed primary sequence homology to the recently delineated
      beta-defensin family, heretofore found only in the respiratory epithelial cells
      and neutrophils of cattle, suggesting that beta-defensins originated at least 250
      million years ago, before avian and mammalian lineages diverged. The 9 invariant
      residues (6 cysteines, 2 glycines and 1 proline) common to avian gallinacins and
      bovine beta-defensins are likely to constitute the essential primary structural
      motif of this ancient family of host-defense peptides.

PMID- 8150086
TI  - Serotonin release and cell proliferation are under the control of alpha
      bungarotoxin-sensitive nicotinic receptors in small-cell lung carcinoma cell
      lines.
AB  - Neuronal type nicotinic acetylcholine receptors (nAchRs) have recently been
      identified in small-cell lung carcinoma. We here show that both nicotine and
      cytisine stimulate [3H]serotonin release in a dose-dependent manner; this effect
      is antagonized by alpha-bungarotoxin (alpha Bgtx) and alpha-conotoxin MI (alpha
      Ctx). Nicotine and cytisine stimulate in vitro SCLC proliferation and this effect
      is completely antagonized by both alpha Bgtx and alpha Ctx. By PCR analysis, we
      demonstrate the presence in SCLC of both the alpha 7 and the beta 2 nAchR
      subunits mRNA. These data show that nAchRs play an important role in the biology
      of SCLC, and that alpha Bgtx-sensitive receptors of the alpha 7 subtype are
      crucially involved in both the secretagogue and mitogenic effects of nicotinic
      agonists.

PMID- 8150087
TI  - 1 kb of the lactase-phlorizin hydrolase promoter directs post-weaning decline and
      small intestinal-specific expression in transgenic mice.
AB  - Adult-type hypolactasia is a genetic condition making approximately one half of
      the human population intolerant to milk because of abdominal symptoms. The cause
      is a post-weaning down-regulation of the intestinal-specific enzyme lactase
      phlorizin hydrolase (LPH) reducing the intestinal capacity to hydrolyze lactose.
      We here demonstrate that the stretch -17 to -994 in the pig LPH-promoter carries
      cis-elements which direct a small intestinal-specific expression and a post
      weaning decline of a linked rabbit beta-globin gene. These data demonstrate that
      the post-weaning decline of LPH is mainly due to a transcriptional down
      regulation.

PMID- 8150088
TI  - Two intestinal specific nuclear factors binding to the lactase-phlorizin
      hydrolase and sucrase-isomaltase promoters are functionally related oligomeric
      molecules.
AB  - Lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) are enterocyte
      specific gene products. The identification of regulatory cis-elements in the
      promoter of these two genes has enabled us to carry out comparative studies of
      the corresponding intestinal-specific nuclear factors (NF-LPH1 and SIF1-BP).
      Electrophoretic mobility shift assays demonstrated that the two nuclear factors
      compete for binding on the same cis-elements. The molecular size of the DNA
      binding polypeptide is estimated to be approximately 50 kDa for both factors. In
      the native form the factors are found as 250 kDa oligomeric complexes. Based on
      these results NF-LPH1 and SIF1-BP are suggested to be either identical or closely
      related molecules.

PMID- 8150089
TI  - Processing and transport of human small intestinal lactase-phlorizin hydrolase
      (LPH). Role of N-linked oligosaccharide modification.
AB  - The effect of glycosylation on the intracellular transport of human intestinal
      lactase-phlorizin hydrolase (LPH) was investigated by biosynthetic labeling of
      biopsy samples in the presence or absence of glycosidase inhibitors. In the
      presence of deoxynojirimycin (dNM) and deoxymannojirimycin (dMM), endo H
      sensitive LPH glycoforms of M(r) = 135,000 in both cases were produced (LPHdNM
      and LPHdMM). The LPH glycoform generated in the presence of swainsonine had an
      apparent molecular mass of 141,000 (LPHSwa) and was partially sensitive to endo
      H. By contrast to unmodified mature LPH (LPHm, M(r) = 160,000), these glycoforms
      are either not O-glycosylated (LPHdNM and LPHdMM) or partially O-glycosylated
      (LPHSwa) indicating that processing of N-linked carbohydrates has direct effects
      on the O-glycosylation of pro-LPH. Analysis of transport kinetics of the various
      glycoforms strongly suggested that carbohydrate modification does not affect the
      transport of pro-LPH from the cis-Golgi to the cell surface, but could be rate
      limiting at the level of the ER.

PMID- 8150090
TI  - The mechanisms and regulation of procathepsin L secretion from osteoclasts in
      bone resorption.
AB  - The secretion mechanisms of cathepsin L from osteoclasts in the process of bone
      resorption were investigated. The increases in bone pit numbers formed take place
      by PTH addition in parallel with the increases of cathepsin L and/or L-like
      proteinase activities in the culture medium of bone cells, and these were
      suppressed by the addition of calcitonin. The Z-Phe-Arg-MCA hydrolysing activity
      increased in the medium through the effect of PTH is considered to be a kind of
      procathepsin L by Western blotting analysis, and was suppressed by calcitonin
      addition. Furthermore, monensin inhibited not only the PTH-induced pit formation,
      but also cysteine proteinase activity in osteoclasts. Therefore, the procathepsin
      L excreted might be transferred from endothelial reticulum via Golgi and/or via
      lysosomes.

PMID- 8150091
TI  - Highly polarized expression of carbohydrate-binding protein p33/41 (annexin IV)
      on the apical plasma membrane of epithelial cells in renal proximal tubules.
AB  - p33/41 is a Ca(2+)-dependent carbohydrate-binding protein and is identical to
      annexin IV, a member of the annexin protein family. The localization of p33/41 in
      bovine kidney specimens was investigated immunohistochemically by use of specific
      polyclonal antibodies. The most interesting finding on immunostaining was that
      p33/41 was highly concentrated in the apical plasma membrane of the epithelial
      cells in the proximal tubules contrary to the distribution throughout the
      cytoplasm in the papillary ducts and papilla epithelium. The enrichment of p33/41
      in the apical membrane was confirmed by immunoblotting of the brush border
      membrane fraction prepared from a kidney homogenate. Sequential extraction with
      EDTA and Triton X-100, and a partition experiment with Triton X-114 revealed that
      most p33/41 associates with the renal brush border membrane in a Ca(2+)
      independent manner and is integrated into the membrane like intrinsic membrane
      proteins.

PMID- 8150092
TI  - Structural differences in chlorosomes from Chloroflexus aurantiacus grown under
      different conditions support the BChl c-binding function of the 5.7 kDa
      polypeptide.
AB  - Structurally different chlorosomes were isolated from the green photosynthetic
      bacterium Chloroflexus aurantiacus grown under different conditions. They were
      analysed with respect to variable pigment-protein stoichiometries in view of the
      presumed BChl c-binding function of the 5.7 kDa chlorosome polypeptide. Under
      high-light conditions on substrate-limited growth medium the pigment-protein
      ratio of isolated chlorosomes was several times lower than under low-light
      conditions on complex medium. Proteolytic degradation of the 5.7 kDa polypeptide
      in high-light chlorosomes led to a 60% decrease of the absorbance at 740 nm. The
      CD spectrum of high-light chlorosomes exhibited a sixfold lower relative
      intensity at 740 nm (delta A/A740) than low-light chlorosomes, but it showed a
      fivefold increase in intensity upon degradation of the 5.7 kDa polypeptide
      compared to a twofold increase in low-light chlorosomes. It seems probable that
      BChl c in the chlorosomes is present as oligomers bound to the 5.7 kDa
      polypeptide. Our data suggest further that compared to low-light chlorosomes
      smaller oligomers or single BChl c molecules are bound to the 5.7 kDa polypeptide
      in high-light chlorosomes resulting in lower rotational strength.

PMID- 8150093
TI  - Molecular cloning of the S-adenosylmethionine synthetase gene in Drosophila
      melanogaster.
AB  - We have isolated and sequenced cDNA clones encoding the Drosophila melanogaster S
      adenosylmethionine synthetase. The deduced amino acid sequence contains 405 amino
      acid residues and shows high homology to rat, yeast, Arabidopsis and Escherichia
      coli counterparts. The gene is transcribed throughout Drosophila development but
      its main activity is seen in adult males and females. The highest transcription
      activity is seen in female ovaries. The transcript has an unusually long 5'
      untranslated region, which might be of importance for translational regulation.

PMID- 8150094
TI  - Strong affinity of Maackia amurensis hemagglutinin (MAH) for sialic acid
      containing Ser/Thr-linked carbohydrate chains of N-terminal octapeptides from
      human glycophorin A.
AB  - The interaction of the Maackia amurensis hemagglutinin (MAH) with various
      glycopeptides and oligosaccharides was investigated by means of immobilized
      lectin affinity chromatography. An amino terminal octapeptide obtained from human
      glycophorin A having three Neu5Ac alpha 2-->3Gal beta 1-->3(Neu5Ac alpha 2-
      >6)GalNAc tetrasaccharide chains, designated as CB-II, was found to have an
      extremely strong affinity for MAH. Therefore, it is strongly suggested that
      hemagglutination by MAH was caused by its interaction with Ser/Thr-linked
      carbohydrate chains of human glycophorin A on erythrocyte membranes.

PMID- 8150095
TI  - Comparative study of different laser systems.
AB  - OBJECTIVE: To review lasers, laser physics, laser-tissue interaction, delivery
      systems, and their clinical applications relevant to gynecology. SETTINGS:
      Gynecological Service at Massachusetts General Hospital (MGH) and MGH Laser
      Center. INTERVENTIONS: None. DESIGN: Laser literature review and personal
      experiences of the authors were used to prepare this manuscript. CONCLUSIONS:
      Lasers have been used in gynecologic practice for cutting and coagulating
      purposes. Photodynamic therapy has been used clinically for malignant conditions
      and is being investigated for dysplastic lesions of the lower genital tract and
      for endometrial ablation. Laser welding has potential, but further work is
      required in this field before it finds a clinical application. The main lasers
      used in gynecology are CO2, neodymium-yttrium aluminum garnet (Nd:YAG), and
      potassium tatanyl-phosphate-doubled Nd:YAG. Pulsed Ho:YAG laser looks promising,
      as does diode lasers. Holmium-yttrium aluminum garnet and diode lasers will be
      soon available commercially. Improvements in delivery systems have increased user
      friendliness, and more developments in this area are anticipated, for example, a
      fiber-optic delivery system for CO2 lasers. We believe that enhanced
      understanding of laser technology will provide unique applications for
      development in gynecology.

PMID- 8150096
TI  - International consensus conference on postmenopausal hormone therapy and the
      cardiovascular system.

PMID- 8150097
TI  - Dyssynchrony in the maturation of endometrial glands and stroma.

PMID- 8150098
TI  - Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory
      women.
AB  - OBJECTIVE: To determine whether weight loss in obese, hyperandrogenic,
      anovulatory women is associated with resumption of ovulation and/or with changes
      in insulin, androgen, and gonadotropin concentrations. DESIGN: Prospective,
      randomized, controlled study. SETTING: University research center. PATIENTS:
      Twelve obese, hyperandrogenic, anovulatory women. INTERVENTIONS: Twelve-week
      weight loss program in treatment (n = 6); 12-week "waiting list" in control group
      (n = 6). MAIN OUTCOME MEASURES: [1] Ovulation; [2] fasting insulin and glucose
      measurements; [3] sex hormone-binding globulin (SHBG), total and non-SHBG T
      concentrations; [4] LH pulse frequency, amplitude, and concentration; and [5] FSH
      concentration. RESULTS: In contrast with the control group who showed no change
      in weight, ovulation status, or hormone levels, women in the treatment group lost
      an average of 16.2 kg and showed a significant increase in SHBG, a significant
      decline in non-SHBG T, and a decline (though nonsignificant) in fasting insulin.
      Four of six subjects resumed ovulation. However, no changes were evident in LH
      pulse frequency or amplitude or in mean LH and FSH concentrations. CONCLUSIONS:
      Weight loss in obese, hyperandrogenic, anovulatory women appears to reduce
      insulin and non-SHBG T concentrations despite the absence of a change in
      gonadotropin secretion and may lead to resumption of ovulation.

PMID- 8150099
TI  - Insulin sensitivity in women with polycystic ovary syndrome: relationship to
      hyperandrogenemia.
AB  - OBJECTIVE: To evaluate the extent of decreased insulin sensitivity in relation to
      body mass index and its relationship to serum androgens in women with polycystic
      ovarian syndrome (PCOS). DESIGN: Comparative study of endogenous glucose disposal
      and serum insulin responses to oral glucose load with endocrine parameters in
      PCOS. SETTING: Fertility and Endocrine Clinics, North Staffordshire Hospital
      Centre. PATIENTS: Forty-nine obese and 16 nonobese women with PCOS were compared
      with 18 obese and 16 nonobese control women with regular ovulatory cycles and no
      features of PCOS. MAIN OUTCOME MEASURES: Basal concentrations of serum LH, FSH,
      T, androstenedione, sex hormone-binding globulin (SHBG), and free T index.
      Measurements of insulin sensitivity by rate of endogenous glucose disposal after
      i.v. bolus injection of insulin and glucose mediated insulin responses. RESULTS:
      Obese women with PCOS showed decreased insulin sensitivity and hyperinsulinemia
      to an extent greater than can be explained by obesity alone. Serum insulin showed
      inverse correlation with SHBG, and therefore hyperinsulinemia increased the
      bioavailability of androgens in obese PCOS. In nonobese PCOS, this method of
      assessment failed to reveal insulin resistance. CONCLUSION: Hyperandrogenemia and
      insulin resistance are independent features of PCOS. Hyperinsulinemia enhances
      expression of hyperandrogenemia by increasing bioavailability of androgens.

PMID- 8150100
TI  - Comparison of the efficacy of spironolactone versus flutamide in the treatment of
      hirsutism.
AB  - OBJECTIVE: To compare the efficacy of two antiandrogens, spironolactone and
      flutamide, in the treatment of hirsutism. PATIENTS, PARTICIPANTS: Twenty women
      with idiopathic hirsutism were randomized to receive either flutamide or
      spironolactone. DESIGN: Twenty hirsute women were recruited from patients
      presenting to the hirsutism clinic in Marmara University, Istanbul. Each patient
      underwent a complete medical and gynecological examination as well as endocrine
      profile, hematologic, hepatic, and renal function analyses. Hirsutism scores were
      determined according to the Ferriman-Gallwey scoring system. These tests were
      then repeated at 3, 6, and 9 months of therapy. Ten patients received 250 mg of
      flutamide two times per day, and 10 patients received 100 mg of spironolactone
      for 9 months. RESULTS: Ferriman-Gallwey scores were decreased significantly in
      both groups at the end of 9 months. The percent of change in hirsutism scores in
      flutamide and spironolactone group were as follows: 26.4% and 20.9% at 3 months;
      39.5% and 32.9% at 6 months; and 46.4% and 39.6% at 9 months, respectively. There
      was a trend toward a better response with flutamide that did not achieve
      significance. None of the hormonal parameters changed significantly during this
      period of time. Irregular bleeding was observed in five patients (50%) of the
      spironolactone group, whereas none of the patients in the flutamide group
      experienced menstrual irregularity. Conversely, dry skin and increased appetite
      were experienced by two patients (20%) in the flutamide group but not in the
      spironolactone group. CONCLUSION: These data suggest that both spironolactone and
      flutamide were similarly effective in treatment of hirsutism, and the pure
      antiandrogen flutamide is a safe and effective alternative in treatment.

PMID- 8150101
TI  - Plasma insulin-like growth factor-I, CA-125, estrogen, and progesterone in women
      with leiomyomas.
AB  - OBJECTIVE: To determine plasma levels of insulin-like growth factor-I (IGF-I), CA
      125, estrone (E1), E2, and P in women with uterine leiomyomas compared with
      normal women. DESIGN: Women with leiomyomas were compared with normal women
      (control). SETTING: University Department of Obstetrics and Gynecology. PATIENTS:
      Fifty-one premenopausal women with uterine myomas > 14 weeks gestation and 30
      normal fertile women (controls) were studied. Peripheral blood samples were
      obtained before myomectomy or hysterectomy and during the nonmenstruating phase
      in the controls. MAIN OUTCOME MEASURES: Plasma levels of E1, E2, P, CA-125, and
      IGF-I were determined by specific and sensitive RIAs and immunoradiometric
      assays. RESULTS: Plasma IGF-I levels were 2,006 +/- 185 mU/mL (mean +/- SEM, n =
      35) and 2,335 +/- 287 mU/mL (n = 16) in women with leiomyomas during the
      follicular and luteal phases, respectively, whereas the corresponding values for
      normal women were 1,702 +/- 120 (n = 30) and 1,774 +/- 239 mU/mL (n = 30).
      Similarly, plasma CA-125 levels were unchanged in women with leiomyomas (myomas:
      18.8 +/- 2.4, 21.5 +/- 3.7 U/mL; normal: 15.9 +/- 1.5, 15.8 +/- 1.3 U/mL during
      follicular and luteal phases, respectively). Women with leiomyomas had plasma E1,
      E2, and P levels during the follicular phase (91.9 +/- 11.5 pg/mL; conversion
      factor to SI unit, 3.699; 94.6 +/- 19.0 pg/mL; conversion factor to SI unit,
      3.671; and 1.5 +/- 0.4 ng/mL; conversion factor to SI unit, 3.180, respectively)
      and the luteal phase (105.8 +/- 11.2 pg/mL; conversion factor to SI unit, 3.699;
      128.7 +/- 24.8 pg/mL; conversion factor to SI unit, 3.671; and 9.6 +/- 1.6 ng/mL;
      conversion factor to SI unit, 3.180) similar to normal women. CONCLUSION: Plasma
      levels of IGF-I, CA-125, E1, E2, and P are normal in women with leiomyomas.

PMID- 8150102
TI  - Evaluation of leuprolide acetate treatment on histopathology of uterine myomata.
AB  - OBJECTIVE: To determine if short-term, preoperative leuprolide acetate (LA)
      therapy alters the histologic appearance of uterine leiomyomata. DESIGN:
      Retrospective evaluation by a pathologist (who was blinded to patient history) of
      the histologic features of leiomyomata excised from 36 women, 12 who received
      preoperative LA and 24 age-matched controls. SETTING: Yale-New Haven Hospital,
      New Haven, Connecticut, from September 1989 to September 1990. MAIN OUTCOME
      MEASURE: The histologic specimens were evaluated for the presence of mitotic
      activity, cellular atypia, cellularity, and secondary changes including edema,
      fibrosis, calcification, hemorrhage, infarction, hyalinization, and vascular
      appearance. RESULTS: Of the 12 patients treated with LA, 10 (84%) demonstrated a
      reduction in uterine volume after 3 to 6 months of LA therapy. There was no
      difference in any of the histopathologic parameters evaluated between the LA
      treated group and the untreated group. Exclusion of leiomyoma, which did not have
      a reduction in size during LA therapy, did not alter the analysis. Among patients
      treated with LA, those leiomyoma that did not respond to LA had a greater degree
      of hyalinization than those that responded. CONCLUSION: Reduction in uterine size
      by short-term LA therapy did not detectably alter histologic appearance of
      leiomyoma.

PMID- 8150103
TI  - Serum human chorionic gonadotropin dynamics during spontaneous resolution of
      ectopic pregnancy.
AB  - OBJECTIVE: To study serum hCG dynamics in patients with ectopic pregnancy (EP)
      selected for expectant management. DESIGN: A prospective observational study.
      SETTING: Helsinki University Central Hospital, Helsinki, Finland. SUBJECTS: One
      hundred eighteen patients, who were selected for expectant management among 493
      patients with EP. INTERVENTIONS: Patients were examined every 1 to 3 days using
      transvaginal sonography and serum hCG determinations until hCG values < 10 IU/L
      (conversion factor to SI unit, 1 IU/L = 2.93 pmol/L) were reached. Laparoscopy
      was performed if the patient developed abdominal pains or intra-abdominal
      hemorrhage as revealed by sonography. MAIN OUTCOME MEASURE: Serum hCG level.
      RESULTS: The median gestational age at the start of follow-up in patients with a
      spontaneous resolution was 44 days and in patients requiring laparoscopy was 48
      days. The success rate for a spontaneous resolution was 88% when the initial hCG
      level was < 200 IU/L but only 25% at levels > 2,000 IU/L. In the 77 patients with
      a spontaneous resolution, the initial median hCG concentration was 374 IU/L
      (range, 20 to 10,762 IU/L) and it decreased to normal in 4 to 67 days (mean, 20
      days). In the 41 patients requiring laparoscopy the median initial hCG
      concentration was 741 IU/L (range, 165 to 14,047 IU/L); a normal level was
      reached in 3 to 43 days (mean, 12 days) after operation. Follow-up period before
      operation was 1 to 24 days (mean, 9 days). Laparoscopy was indicated in two
      thirds of the patients with a serum hCG level > 64% of the initial value after 7
      days of follow-up. CONCLUSIONS: Spontaneous resolution of EP correlated with a
      low and rapidly decreasing hCG level.

PMID- 8150104
TI  - Characterization of the normal progesterone and placental protein 14 responses to
      human chorionic gonadotropin stimulation in the luteal phase.
AB  - OBJECTIVE: To examine whether midluteal phase administration of the luteotrophic
      hormone hCG can result in higher and more stable serum levels than random
      sampling of P and placental protein 14 (PP14). DESIGN: Prospective controlled
      clinical study. SETTING: Normal human volunteers in an academic research
      environment. PARTICIPANTS: Twenty-six fertile, regularly cycling women.
      INTERVENTIONS: Blood samples were drawn at 0, 3, 6, 9, 12, 18, and 24 hours and
      then daily for the next 6 days, after a single IM injection of 5,000 IU hCG or
      saline given on day 5, 7, or 9 after the LH surge, as detected by rapid plasma
      assays. MAIN OUTCOME MEASURES: Serum P and PP14 measurements. RESULTS: Peak P and
      PP14 concentrations occurred at 6 hours and 5 days, respectively, after hCG
      stimulation on luteal phase day 9. Progesterone but not PP14 levels were
      significantly higher and less variable after hCG than after saline administration
      on this day. Progesterone responses exceeded 11.0 ng/mL (35.0 nmol/L) in all
      women, suggesting that this represents the cutoff limit for normal luteal
      function. Because PP14 responses were highly variable and inconsistent, it was
      not possible to determine a threshold for normal endometrial function.
      CONCLUSIONS: Midluteal phase administration of hCG in normal women induces
      consistent serum P levels > 11.0 ng/mL (35.0 nmol/L) but highly variable PP14
      responses.

PMID- 8150105
TI  - Pharmacokinetics of a triphasic oral contraceptive containing desogestrel and
      ethinyl estradiol.
AB  - OBJECTIVE: To demonstrate that pharmacokinetic measurements were made at steady
      state. Subsequently, dose proportionality for desogestrel and ethinyl E2 kinetics
      were demonstrated. DESIGN: Open-label, noncomparative study. SETTING: Healthy
      volunteers in an academic research environment. PARTICIPANTS: Twenty white women
      who were 19 to 32 years old were solicited via an advertisement. Nineteen of the
      20 women completed the study. INTERVENTIONS: Study medication consisted of three
      cycles of a triphasic oral contraceptive containing desogestrel and ethinyl E2.
      Blood samples were taken at baseline and during cycle 3 between -48 and 24 hours
      on days 1, 7, 14, and 21, with additional sampling times on day 21 at 48, 60, and
      72 hours. MAIN OUTCOME MEASURES: Serum concentrations of 3-keto-desogestrel and
      ethinyl E2. RESULTS: Evaluation of the trough serum levels indicated that a
      steady state of 3-keto-desogestrel had been reached. Statistical analysis on the
      Cmax, area under the curve (AUC), and Css,min indicated dose proportionality for
      the administered desogestrel. Ethinyl E2 serum levels obtained at the same time
      points also reflected steady state levels and showed minimal variability. The
      statistical analysis on Cmax, AUC, Css,min, and Tmax indicated that the
      pharmacokinetics of ethinyl E2 on days 7, 14, and 21 were not statistically
      significantly different, indicating dose equivalency. CONCLUSIONS: Steady state
      of 3-keto-desogestrel is reached after each of the three phases and the
      pharmacokinetics are dose proportional. After reaching steady state, the
      pharmacokinetics of ethinyl E2 remain constant over time.

PMID- 8150106
TI  - Impaired follicular growth and abnormal luteinizing hormone surge in luteal phase
      defect.
AB  - OBJECTIVE: To determine whether luteal phase defect (LPD) is associated with
      follicular growth or LH surge. DESIGN: The length of luteal phase was determined
      by the date of ovulation assessed by serial ultrasound measurements of follicle
      growth on a daily basis. Luteal phase defect was defined when the length of the
      luteal phase was < 11 days and/or the midluteal serum P level was < 10 ng/mL
      (31.8 nmol/L). Preovulatory follicular growth was examined by transvaginal
      ultrasonography. Blood samples taken at midluteal phase were assayed for P. Urine
      LH levels were determined in samples collected twice a day during periovulatory
      cycles using rapid urinary assay kits. SETTING: Infertility outpatient clinic,
      Tokyo University Hospital. PATIENTS: Eighty-one menstrual cycles from 63 normally
      cycling infertile women who were not administered any medications. RESULTS:
      Thirty-six of 81 cycles showed LPD. The mean +/- SD maximal preovulatory
      follicular diameter was significantly smaller in LPD cycles than in non-LPD
      cycles (16.5 +/- 2.7 versus 19.0 +/- 2.8 mm). The mean +/- SD peak level of
      urinary LH surge was significantly lower in LPD cycles compared with non-LPD
      cycles (50 +/- 25 versus 65 +/- 21 IU/L). Luteal phase defect cycles showed a
      relatively high incidence of abnormal LH surges, namely, lower peak levels or
      prolonged duration. CONCLUSIONS: Luteal phase defect was associated with impaired
      follicular growth and/or abnormal LH surge. These factors may be involved in the
      pathogenesis of LPD.

PMID- 8150107
TI  - Elevation of the phospholipase A2 activity in peritoneal fluid cells from women
      with endometriosis.
AB  - OBJECTIVE: To assess the prostaglandin (PG) production on peritoneal fluid (PF)
      cells, phospholipase A2 (PLA2) activity of those cells in women with
      endometriosis was measured and compared with that of women without endometriosis.
      DESIGN: Prospective clinical controlled study. PATIENTS: Women who underwent
      laparoscopy and were found either to have endometriosis (n = 15) or not (n = 9)
      were included in this study. Mononuclear cells obtained from the patients at
      laparoscopy were immediately separated by a Ficoll-Paque technique, lysed by
      nitrogen cavitation, and stored at -80 degrees C. INTERVENTIONS: Phospholipase A2
      activity was measured by Dole assay using 1-palmitoyl-2-[1-14C] palmitoyl
      phosphatidyl choline and assessed on a protein basis and a cell number basis.
      RESULTS: There were at least four measurable kinds of PLA2 activity detected in
      the cells: two calcium-dependent pH optima 7.0 and 9.0 activities and two calcium
      independent pH optima 7.5 and 8.5 activities. A calcium-dependent and pH optima
      9.0 activity was the highest, and it was significantly higher in women with
      endometriosis when compared with those who did not have endometriosis.
      CONCLUSION: These results indicate that the increase in the PGs in PF with
      endometriosis may be produced by PF cells in which PLA2 activity is elevated.

PMID- 8150108
TI  - Effects of aging on the human ovary: the secretion of immunoreactive alpha
      inhibin and progesterone.
AB  - OBJECTIVE: To investigate the changes induced by age in the function and
      secretory pattern of the human ovary. Immunoreactive alpha-inhibin, E2, and P
      secretion in vivo and in vitro have been compared in two different populations.
      DESIGN: Prospective study. Women undergoing IVF-ET were divided into two groups
      according to age: group 1 (32.0 +/- 0.7 years; mean +/- SEM) and group 2 (40.3 +/
      0.3 years). SETTING: In vitro fertilization program at the Instituto Valenciano
      de Infertilidad. PATIENTS: A total of 33 infertile women with regular menses,
      undergoing IVF-ET. INTERVENTIONS: Follicle aspiration performed by transvaginal
      ultrasound. Four follicles per patient were aspirated in individual plastic
      tubes. Granulosa-luteal cells isolated with Percoll columns and cultured in vitro
      up to 4 days in the presence of hCG. MAIN OUTCOME MEASURES: In vitro
      fertilization parameters, serum levels of E2, immunoreactive alpha-inhibin, and
      P, as well as the secretion of immunoreactive alpha-inhibin and P by the cultured
      granulosa-luteal cells. RESULTS: Serum immunoreactive alpha-inhibin levels the
      day of ovum pick-up were significantly lower in group 2 compared with group 1.
      Incubation of cells for 96 hours showed a significantly higher ability to
      accumulate immunoreactive alpha-inhibin in group 1 than 2. Human chorionic
      gonadotropin stimulated immunoreactive alpha-inhibin production after 96 hours.
      Cells from younger women displayed a significantly higher ability to secrete P
      than cells from older women. Human chorionic gonadotropin was able to
      significantly stimulate P production in group 1. CONCLUSIONS: These results
      confirm previous observations showing a reduced production of immunoreactive
      alpha-inhibin and steroids of ovaries from older women and suggest that a reduced
      cellular function, rather than a decrease in the follicular population, is the
      main mechanism by which these changes are produced.

PMID- 8150109
TI  - Clinical pharmacology of recombinant human follicle-stimulating hormone (FSH). I.
      Comparative pharmacokinetics with urinary human FSH.
AB  - OBJECTIVE: To assess and compare the pharmacokinetics of recombinant human FSH
      with those of a reference preparation of urinary human FSH. DESIGN: Urinary human
      FSH and recombinant human FSH (Metrodin and Gonal-F; Laboratoires Serono,
      Aubonne, Switzerland) were administered in a balanced, random order, crossover
      sequence as a single i.v. dose of 150 or 300 IU separated by 1 week of washout to
      12 pituitary down-regulated, healthy female volunteers. Serum FSH concentrations
      were measured by an immunoradiometric assay (IRMA) and by an in vitro rat
      granulosa cell aromatase bioassay. Urine FSH concentrations were measured by
      IRMA. RESULTS: The mean concentration-time profiles after 150 IU of urinary human
      FSH and recombinant human FSH were superimposed, and the mean profile after 300
      IU of recombinant human FSH was double that of the 150 IU dose. The data for both
      FSH preparations were well described by a biexponential equation. Total clearance
      of the preparations was comparable, judging from immunoassay and bioassay data
      (0.5 and 0.15 L/h, respectively). Based on the immunoassay, renal clearance of
      urinary human FSH was 0.1 L/h, whereas for recombinant human FSH it was slightly
      lower at 0.07 L/h, indicating that less than one fifth of the administered dose
      was excreted in the urine. Immunoassay showed that the two preparations were
      similar in terms of initial and terminal half-lives (2 and 17 hours,
      respectively). The volumes of distribution at steady state (11 L) were similar.
      The results of the in vitro bioassay confirmed this pharmacokinetic analysis.
      Just after i.v. administration, an initial decrease in the serum
      bioassay:immunoassay ratio was observed because of dilution of urinary human FSH
      or of recombinant human FSH in the residual endogenous FSH pool. Then the ratio
      increased progressively with time, suggesting either metabolic selection or
      activation of both types of injected human FSH toward forms with greater in vitro
      bioactivity. The bioassay:immunoassay ratio returned to baseline by day 7.
      CONCLUSION: The results obtained in this study indicate that the following [1]
      the pharmacokinetic characteristics of recombinant human FSH are similar to those
      of urinary human FSH; [2] the terminal half-life of human FSH is approximately 1
      day; [3] after a single i.v. injection of human FSH a progressive increase in FSH
      bioassay: immunoassay ratio is observed; and [4] clinical use of recombinant
      human FSH could follow protocols and treatment regimens currently applied to
      urinary human FSH.

PMID- 8150110
TI  - Clinical pharmacology of recombinant human follicle-stimulating hormone. II.
      Single doses and steady state pharmacokinetics.
AB  - OBJECTIVE: To assess the single-dose pharmacokinetics of a recombinant human FSH
      preparation (Gonal-F; Laboratoires Serono, Aubonne, Switzerland), administered by
      i.v., IM, and SC routes and its pharmacokinetics at steady state after multiple
      dosing by the SC route. DESIGN: Twelve healthy down-regulated female volunteers
      received in random order three single doses of recombinant human FSH (150 IU,
      i.v., IM, and SC), with each administration separated by 1 week. The volunteers
      then received multiple recombinant human FSH doses by the SC route (150 IU one
      time per day) for 7 days. Follicle-stimulating hormone concentrations were
      measured by an immunoradiometric assay and an in vitro granulosa cell aromatase
      bioassay. RESULTS: After a single administration, the pharmacokinetics of
      recombinant human FSH were well-described by a two-compartment model after i.v.
      administration and by a one-compartment model with first order absorption after
      IM or SC administration. The mean total clearance of FSH was approximately 0.6
      L/h, and renal clearance accounted for one tenth of the total elimination after
      i.v. administration. The distribution half-life was close to 2 hours. The
      terminal half-life was nearly 1 day when estimated either by modeling the i.v.
      data set or from analysis of the terminal phase of the steady state
      pharmacokinetic curve or from the time taken to reach steady state after repeated
      SC administrations. After single IM and SC injection, two thirds of the
      administered dose was available systemically. The cumulation factor for repeated
      SC administration was approximately 3 when steady state was reached. The in vitro
      bioassay data confirmed these estimations. The temporal evolution of the
      bioassay:immunoassay ratio suggests either metabolic selection or activation of
      recombinant human FSH toward forms with greater in vitro bioactivity. CONCLUSION:
      The estimation of the elimination half-life of approximately 1 day indicates that
      the maximal effect of a given dose of recombinant human FSH administered daily
      cannot be observed until 3 to 4 days of repeated administration. This indicates
      that, on a pure pharmacokinetic basis, physicians should wait at least 4 days to
      assess the efficacy of a given dose of recombinant human FSH and that they should
      not modify dosage too frequently.

PMID- 8150111
TI  - Clinical pharmacology of recombinant human follicle-stimulating hormone. III.
      Pharmacokinetic-pharmacodynamic modeling after repeated subcutaneous
      administration.
AB  - OBJECTIVE: To investigate the respective role of the pharmacokinetic and of the
      pharmacodynamic characteristics in individual variability and to reassess the
      time course and the informative value of FSH pharmacodynamic markers by applying
      a combined pharmacokinetic-pharmacodynamic modeling analysis. DESIGN: After a 1
      week SC administration of 150 IU/d of recombinant human FSH (Gonal-F;
      Laboratoires Serono, Aubonne, Switzerland) to 12 healthy down-regulated female
      volunteers, inhibin and E2 serum level and total follicular volume were recorded
      at preset times during 2 weeks. RESULTS: Good correlations were obtained between
      inhibin maximal levels and maximal total follicular volumes and between E2
      maximal serum level increases and maximal total follicular volumes. In contrast,
      no correlation was found between maximal serum concentration of FSH and any of
      the recorded effects. Pharmacodynamic effects started to increase significantly
      later than FSH serum concentration, especially for E2 serum level and total
      follicular volume. Inhibin serum level was the first pharmacodynamic marker to
      increase. A full pharmacokinetic-pharmacodynamic model was developed to determine
      the relationship between drug concentrations and FSH pharmacological effects.
      This approach provides a better understanding of the concentration-effect
      relationship and should allow a rational design for recombinant human FSH dose
      regimen. The average equilibration half-life between serum concentrations and
      theoretical effect-compartment concentrations is approximately 2 days for inhibin
      and approximately 4 days for E2, indicating that inhibin serum levels are
      tracking FSH concentrations more closely than E2 serum levels. CONCLUSIONS: [1]
      Recombinant human FSH alone is effective to stimulate ovarian follicular
      development and steroidogenesis in women pretreated with a GnRH agonist despite
      complete LH suppression; [2] there is a large interindividual variability in the
      response to recombinant human FSH; [3] this variability is mainly related to
      ovarian sensitivity to FSH rather than difference in pharmacokinetics; [4]
      inhibin is an early index of follicular development, further supporting its role
      as a putative tool to monitor FSH therapy; and [5] a slow stepwise increase in
      FSH dose is recommended if FSH overexposure and excessive ovarian stimulation are
      to be minimized. These observations suggest that recombinant human FSH will in
      the near future replace urinary human FSH in the clinics.

PMID- 8150112
TI  - Endometrial structure after superovulation: a prospective controlled study.
AB  - OBJECTIVE: To demonstrate the effect of superovulation using a GnRH agonist (GnRH
      a) and hMG and hCG on endometrial structure. DESIGN: Prospective, case-controlled
      study. SETTING: Tertiary referral assisted reproduction unit in an academic
      department. PATIENTS: Eleven women undergoing GIFT or IVF, without ET.
      INTERVENTIONS: All women were treated with a long stimulation regimen using the
      depot GnRH-a Goserelin (ICI, Macclesfield, United Kingdom) and hMG and hCG. MAIN
      OUTCOME MEASURES: Comparison of endometrial biopsy specimens taken 4 days after
      ovulation in an unstimulated cycle with specimens taken 4 days after oocyte
      recovery, using standard dating criteria and morphometric analysis. RESULTS:
      There was no difference in endometrial glandular development as assessed by
      either standard criteria or morphometric analysis. CONCLUSIONS: Superovulation
      preceded by pituitary down regulation is not associated with abnormal endometrial
      glandular development, even though supraphysiological levels of E2 and P are
      induced.

PMID- 8150113
TI  - Superovulation with human menopausal gonadotropins is associated with endometrial
      gland-stroma dyssynchrony.
AB  - OBJECTIVE: To investigate the prevalence of endometrial inadequacy in endometrial
      biopsies from women undergoing superovulation with hMG and to correlate these
      findings with the hormonal milieu. DESIGN: Controlled, retrospective analysis.
      SETTING: University-based, tertiary referral, outpatient infertility clinic.
      SUBJECTS: Endometrial biopsies were performed during the late luteal phase in 89
      women undergoing hMG superovulation combined with IUI. Results were compared with
      the initial biopsies obtained as part of their routine infertility evaluation.
      MAIN OUTCOME MEASURES: Biopsies were dated by two different observers using
      standard dating criteria. Serum samples obtained during the midluteal phase were
      assayed in duplicate for E2 and P levels using commercially available RIAs.
      RESULTS: Fifty-seven percent of the endometrial biopsies showed differences in
      the dating of the glandular epithelium that differed by > 2 days when compared
      with the stroma. In contrast, only 13% of endometrial biopsies obtained during a
      nonstimulated cycle showed gland-stroma dyssynchrony. When cycles associated with
      gland-stroma dyssynchrony were compared with cycles associated with coordinated
      development of the glands and stroma, no significant differences were observed in
      E2 level on the day of hCG administration, midluteal serum P, midluteal E2 level,
      or P:E2 ratios. CONCLUSIONS: This study demonstrates that when endometrial
      biopsies are obtained during the late luteal phase in patients undergoing ovarian
      hyperstimulation there is a significant dyssynchrony in the maturation of the
      glandular epithelium and the stroma. This may reflect the degree of
      responsiveness of an individual woman's endometrium rather than a result of the
      hormonal milieu.

PMID- 8150114
TI  - Comparison between nafarelin and leuprolide acetate for in vitro fertilization:
      preliminary clinical study.
AB  - OBJECTIVE: To evaluate the clinical effect of two different biochemical GnRH
      agonists (GnRH-a), nafarelin acetate and leuprolide acetate (LA), as adjunct to
      induction of ovulation in patients for IVF. DESIGN: Twenty-four women were
      assigned randomly to either nafarelin acetate or LA during IVF cycles. SETTING:
      University-affiliated clinics. PATIENTS: Infertile women undergoing IVF cycles in
      an academic research environment. INTERVENTIONS: Intranasal nafarelin at a dosage
      of 200 micrograms twice daily or LA at a dose of 1 mg/d SC was administered.
      Blood samples were collected on day 21 of previous cycle, days 2 and 8, and
      before hCG injection. MAIN OUTCOME MEASURE: Patient response as indicated by
      follicular phase serum levels of E2, FSH, and LH. RESULTS: Hormone profiles on
      cycle day 2 showed no statistical difference between both GnRH-a groups in FSH
      levels and a slight statistical difference for E2 levels. Patient response as
      demonstrated by follicular phase of E2, FSH, and LH measured on cycle day 8 and
      the day of hCG injection showed no statistically significant difference in both
      groups. Furthermore, the mean number of follicles, eggs retrieved, egg quality,
      fertilization rate, and number of embryos transferred and frozen were similar.
      The cycle cancellation rate and pregnancy rate per stimulation start were also
      not statistically different between the two groups. CONCLUSION: The study shows
      the comparable efficacy of these two drugs in controlled ovarian hyperstimulation
      (COH) protocols. The easy administration of nafarelin with prompt nasal
      absorption and the readily achieved blood level made nafarelin an option for use
      in COH in assisted reproductive technology.

PMID- 8150115
TI  - Prospective study of a modified gonadotropin-releasing hormone agonist long
      protocol in an in vitro fertilization program.
AB  - OBJECTIVE: To determine if pituitary suppression is still maintained if GnRH
      agonist (GnRH-a) is discontinued as gonadotropin stimulation is begun in a long
      protocol. DESIGN: Prospective, randomized study. SETTING: An outpatient IVF-GIFT
      program. PATIENTS: One hundred seventy-three patients entering an IVF-GIFT
      program. INTERVENTIONS: Gonadotropin-releasing hormone agonist in long protocol
      was either discontinued or continued as gonadotropin stimulation was begun. MAIN
      OUTCOME MEASURES: Luteinizing hormone (LH), E2, and P levels, egg numbers,
      fertilization rate, number of embryos transferred, day of gonadotropin
      stimulation, and pregnancy rates (PRs). RESULTS: Pituitary suppression was
      maintained although GnRH-a was discontinued as gonadotropin stimulation was
      begun. No spontaneous LH surge was seen, and PRs were increased in the IVF
      patients. CONCLUSION: This study indicates that the advantages gained from use of
      GnRH-a in the long protocol are not compromised by its early discontinuation.

PMID- 8150116
TI  - Assessment of the separation of X- and Y-bearing sperm on albumin gradients using
      double-label fluorescence in situ hybridization.
AB  - OBJECTIVE: To determine the ratio of X- to Y-bearing human spermatozoa in
      fractions isolated from discontinuous albumin gradients. DESIGN: The proportions
      of X- and Y-bearing sperm were determined in neat semen samples (control) and in
      albumin-separated fractions from the same samples. Two albumin methods were used:
      a two-layer method (experiment 1) and a three-layer method (experiment 2). X- and
      Y-bearing sperm were identified simultaneously using chromosome-specific DNA
      probes and fluorescence in situ hybridization. SETTING: Hospital-based university
      department. PARTICIPANTS: Healthy donors with normal semen characteristics. MAIN
      OUTCOME MEASURES: The proportions of haploid cells (X or Y) and cells with two
      sex chromosomes (XX, YY, or XY) were determined. RESULTS: Labeling efficiencies
      were > 96% in all samples. Control samples showed a 1:1 ratio of X- to Y-bearing
      sperm. Fractions isolated on albumin gradients showed a slight, but statistically
      significant enrichment of X-bearing sperm. This was evident with both albumin
      methods. CONCLUSIONS: Discontinuous albumin gradients do not enrich Y-bearing
      sperm as previously reported.

PMID- 8150117
TI  - Sperm quality of subfertile males before and after treatment with human follicle
      stimulating hormone.
AB  - OBJECTIVE: To assess the potential of short-term systemic administration of FSH
      for improving sperm quality, including ultrastructure, in teratozoospermic
      patients having normal endocrine profiles. DESIGN: Semen parameters were assessed
      prospectively using light microscopy (LM), biochemical analysis, and quantitative
      ultramorphological analyses within 2 months before FSH administration and within
      5 days after the end of treatment. SETTING: Samples were collected from patients
      who were referred to the male fertility clinic at Bar-Ilan University. PATIENTS:
      Thirty-one patients with teratozoospermia who exhibited normal hormonal profiles
      and who failed to fertilize their wives in at least two previous IVF attempts (n
      = 17) or who had wives with apparent normal fertility unable to conceive for > or
      = 5 years (n = 14) were classified as subfertile. One hundred one males with no
      previous history of infertility, whose wives conceived after < or = 12 months of
      pregnancy expectation, served as the control group. INTERVENTION: Treatment was
      75 IU FSH administered daily for 30 days. MAIN OUTCOME MEASURES: Pretreatment and
      post-treatment sperm evaluation of basic and quantitative ultramorphological
      analyses parameters. The hypothesis was FSH treatment may improve spermatid
      morphogenesis by its multiple actions on the Sertoli-gamete cell compartment
      without interfering with the testicular hormonogenic function. RESULTS: A
      significant improvement in agenesis of the acrosome and in the amorphous heads
      was observed, reaching normal values after treatment with FSH. The axonema
      deteriorated. No significant changes were observed in basic semen analysis
      parameters. CONCLUSIONS: Because malformations of the fine structure of the sperm
      head subcellular organelles seem to be prerequisites for the success of FSH
      treatment, ultramorphological examination of the sperm may serve as an indication
      for the probability of success of this treatment.

PMID- 8150118
TI  - Impaired hamster egg penetration by human sperm from ejaculates with low acrosin
      activity but otherwise normal.
AB  - OBJECTIVE: To determine if a low acrosin activity in otherwise normal ejaculate
      from infertile patients is associated with an impairment of sperm functions
      involved in the hamster egg penetration. SETTING: A tertiary care center, the
      Andrology Clinic, Department of Internal Medicine, University of L'Aquila.
      PATIENTS: Nine infertile patients with low acrosin activity in otherwise normal
      ejaculate (including normal immunoreactivity for acrosin) were studied; nine
      fertile men served as a control group. The two groups were homogeneous for
      seminal parameters. INTERVENTIONS: The hamster egg penetration assay and the
      acrosome reaction rate assessment were performed on capacitated sperm suspensions
      in basal conditions and after ionophore challenge. MAIN OUTCOME MEASURES: The
      penetration rate, the penetration index, and the acrosome reaction rate were
      measured and compared between the groups. RESULTS: No penetration was achieved in
      seven patients and a low penetration was achieved in two cases. The difference
      with the control group was significant. The ionophore challenge was associated to
      penetration of hamster eggs in seven of nine patients, but the penetration index
      was significantly lower than the controls. Acrosin activity was correlated to
      hamster egg penetration. Both spontaneous and induced acrosome reaction rate were
      similar in the two groups. CONCLUSIONS: A low sperm acrosin activity in otherwise
      normal ejaculate is associated with an impaired hamster egg penetration. This
      impairment does not seem to be due to altered dynamics of acrosome reaction.

PMID- 8150119
TI  - Tissue-type plasminogen activator level is decreased in human seminal plasma with
      abnormal liquefaction.
AB  - OBJECTIVE: To determine plasminogen activators (PAs) and PA inhibitor levels in
      seminal plasma of patients attending an infertility clinic. DESIGN:
      Quantification by immunologic method of PAs in seminal plasma. SETTING: Patients
      of Department of Urology and Andrology, University Hospital, Nimes, France.
      PATIENTS: Ninety-two men attending for assessment because of infertility.
      INTERVENTIONS: Semen were collected by masturbation. Usual sperm parameters were
      determined; immediately after liquefaction, samples were snap-frozen at -85
      degrees C until used for immunologic determination. MAIN OUTCOME MEASURES: Tissue
      type PA antigen, urokinase-type PA antigen, and type 1 PA inhibitor antigen
      levels in seminal plasma. RESULTS: Median values of PA were 270 ng/mL (tissue
      type PA) and 5.4 ng/mL (urokinase-type PA) in normozoospermia; 290 ng/mL (tissue
      type PA) and 5.7 ng/mL (urokinase-type PA) in oligozoospermia; 325 ng/mL (tissue
      type PA) and 3.5 ng/mL (urokinase-type PA) in oligoasthenozoospermia. Type 1 PA
      inhibitor antigen levels were often under detection limit. Tissue-type PA was
      173.5 ng/mL in semen with abnormal liquefaction and 290 ng/mL in semen with
      normal liquefaction. CONCLUSION: The study confirmed the presence of both types
      of PAs in seminal plasma, tissue-type PA being largely predominant. No difference
      was found in tissue-type PA, urokinase-type PA, or type 1 PA inhibitor antigen
      levels between normal and oligozoospermic semen nor between normal and
      asthenozoospermic semen. On the other hand, semen with abnormal liquefaction had
      significantly lower tissue-type PA level than normal semen.

PMID- 8150120
TI  - Quantification of spermatogenesis by dual-parameter flow cytometry.
AB  - OBJECTIVE: To investigate the usefulness of dual-parameter flow cytometry of
      testicular fine-needle aspirates for the quantification of spermatogenesis.
      Immunofluorescence staining for vimentin was introduced to discriminate vimentin
      negative germ cells from vimentin-positive stromal cells. The results of flow
      cytometry were compared with testicular morphology and immunohistochemistry in
      cases of regular and disturbed germ cell maturation. DESIGN: Testicular fine
      needle aspiration and surgical biopsy were performed in 50 autopsy cases. The
      fine-needle aspirates were double stained for the intermediate filament vimentin
      by indirect immunofluorescence and DNA propidium iodide and analyzed by flow
      cytometry. Surgical biopsies were examined by light microscopy. The distribution
      of vimentin-positive cells was evaluated by immunohistochemistry. RESULTS: A
      comparison of morphology and flow cytometric analysis yielded characteristic
      quantitative distribution patterns of the different germ cell and somatic cell
      populations in regular and disturbed spermatogenesis. All three ploidy
      compartments of the germ epithelium correlated with high statistical significance
      with the respective histologic diagnoses. Moreover, a marked quantitative
      increase of stromal cells could be demonstrated in spermatogenetic disorders.
      CONCLUSIONS: The simultaneous analysis of the cellular DNA content and the
      intermediate filament vimentin by flow cytometry enables a detailed investigation
      of spermatogenetic disorders. Quantitative changes of the relationships between
      germ cells and somatic cells can be selectively investigated.

PMID- 8150121
TI  - A quantitative study of sperm head ultrastructure in subfertile males with excess
      sperm precursors.
AB  - OBJECTIVE: To make an objective comparison between sperm head ultrastructure in
      fertile subjects and a subfertile cohort with an excess of immature germinal
      elements in the ejaculate. DESIGN: A quantitative analysis of ultrastructural
      features of the sperm head using transmission electron microscopy in the defined
      groups. PATIENTS: Ten men of proven fertility as controls and 10 subfertile
      subjects with a persistent excess of sperm precursors in the ejaculate were
      investigated. SETTING: The Infertility Clinic at Queen Charlotte's and Chelsea
      Hospital, London. MAIN OUTCOME MEASURES: Each individual in the study achieved a
      score for a range of previously defined features of sperm head ultrastructure.
      These scores provided the basis for comparison between fertile and subfertile
      subjects. RESULTS: Subfertile individuals were found to have motile sperm with
      significantly more hypoplastic, detached, and abnormally shaped acrosomes than
      fertile controls. Sperm nuclei in these subjects also contained significantly
      more intranuclear vacuoles and immature chromatin and were associated more
      commonly with cytoplasmic droplets than fertile controls. CONCLUSION: Men with an
      excess of sperm precursors in the ejaculate have motile sperm with a range of
      abnormalities involving the nucleus and acrosome to account for reduced
      functional competence.

PMID- 8150122
TI  - Expression of a common secretory granule specific protein as a marker for the
      extracellular organelles (prostasomes) in human semen.
AB  - OBJECTIVE: To further characterize prostasomes, trilamellar to multilamellar
      vesicles that are thought to originate from acinar cells of the human prostate
      and present in appreciable amounts in normal human semen. Purified prostasomes
      were shown to have immunosuppressive activity in vitro as measured by inhibition
      of mitogen-induced lymphocyte proliferation and inhibition of superoxide
      generation by neutrophils. A granule membrane protein, called granulophysin, has
      recently been identified in the membranes of platelet dense granules. Antibodies
      that recognize granulophysin also stain granules in different cell types
      including leukocytes, melanocytes, neurones, endothelial cells, and epithelial
      cells. DESIGN: The presence of epitopes recognized by antigranulophysin
      monoclonal antibody in prostasomes was investigated using indirect
      immunofluorescence and subsequent cytofluorimetric analysis. The protein was also
      analyzed by Western blotting. Reactivity of antigranulophysin antibody with the
      prostate tissue was studied by immunoperoxidase staining. RESULTS: A majority of
      prostasome particles specifically reacted with antigranulophysin antibody. In
      lysates prepared from prostasomes, a broad band of 32 to 37 kd was detected by
      Western blotting. CONCLUSION: This report defines granulophysin as a constituent
      membrane molecule of prostasomes that may serve as a useful marker in elucidation
      of prostasome function.

PMID- 8150123
TI  - The formation of coalescing peritoneal adhesions requires injury to both
      contacting peritoneal surfaces.
AB  - OBJECTIVE: To determine whether surgical trauma to one or both contacting
      peritoneal surfaces is necessary to cause coalescing adhesions. SETTING: Research
      laboratory. DESIGN: The abdominal wall peritoneum and one or both contacting
      medial peritoneal surfaces of surgically approximated uterine horns in mice were
      injured by electrocautery, cutting, scratching, or scraping. Adhesion formation
      was assessed visually and histologically 3 and 7 days later. RESULTS: Regardless
      of the type of peritoneal injury, few adhesions resulted when only a single
      injury was made to the abdominal wall (< or = 6%) or to one uterine horn (< or =
      13%). When both opposing uterine surfaces were injured, however, adhesions formed
      at 57% of the sites after electrocautery, 100% after cutting, 100% after
      scratching, but 0% after scraping. When previously created uterine adhesions were
      lysed, they reformed at 15 of 15 sites with and 12 of 13 (92%) sites without
      electrocautery for hemostasis at the time of lysis. CONCLUSIONS: In this murine
      model, the development of postsurgical adhesions required surgical trauma to both
      contacting peritoneal sites, regardless of the type of injury, the mobility of
      the opposing peritoneal surfaces or whether hemostasis was achieved. The clinical
      implications are that more attention needs to be focused on protecting contacting
      normal peritoneal surfaces from inadvertent injury during surgery and that
      different therapeutic strategies may be required for prevention of adhesion
      formation and reformation because of the high probability of contact between
      injured peritoneal surfaces with the latter.

PMID- 8150124
TI  - Sperm morphology and recurrent abortion.
AB  - In 98 men whose partners experienced three or more spontaneous abortions, there
      were no significant differences in ejaculate volume, concentration of sperm, the
      percentage of total abnormal sperm, or the percentage of individual sperm defects
      as compared with normal WHO standards and 17 men fathering successful
      pregnancies. These data indicate that neither abnormal sperm concentration nor
      abnormal sperm morphology are significantly associated with recurrent spontaneous
      abortion.

PMID- 8150125
TI  - The significance of gonadotropin-releasing hormone test for predicting fertility
      after varicocelectomy.
AB  - To predict the surgical outcome in 30 infertile men with varicocele,
      endocrinologic evaluation by the GnRH test was performed before and 6 months
      after the high ligation of the left internal spermatic vein. Semen analysis was
      performed and the levels of basal T and PRL were examined preoperatively and 6
      months postoperatively. In the pregnancy group, the preoperative excessive
      response of LH to the GnRH test decreased significantly after surgery.
      Significant reduction in the LH response is considered to be a valuable parameter
      for predicting fertility.

PMID- 8150126
TI  - Zona drilling and sperm insertion with combined laser microbeam and optical
      tweezers.
AB  - A combined UV-laser microbeam and optical-tweezers trap was used to perform laser
      zona drilling and subzonal insemination in cattle. Using a precisely focused UV
      laser microbeam, a small channel of about 10 microns in diameter was drilled into
      the zona pellucida. With a three-dimensional optical-tweezers trap, a single
      sperm was caught and transported through the laser-drilled hole directly into the
      perivitelline space. Furthermore, the sperm was brought into close contact with
      the oolemma to facilitate sperm-oocyte fusion. Using the laser-microscope system,
      noncontact, entirely sterile, and highly selective micromanipulation of gametes
      can be achieved with no need for mechanical microtools. Laser micromanipulation
      seems to be less detrimental to the gametes and is comparatively is easy to
      perform. Thus, the combined UV-laser microbeam and optical tweezers trap may be a
      helpful tool for IVF procedures.

PMID- 8150127
TI  - Ureteral obstruction--a complication of oocyte retrieval.

PMID- 8150128
TI  - Ureteral obstruction--a complication of oocyte retrieval.

PMID- 8150129
TI  - Language and sea urchins in science.

PMID- 8150130
TI  - Age-related decline in fecundity--cause?

PMID- 8150131
TI  - Age-related decline in fecundity--cause?

PMID- 8150132
TI  - The dangers of downsizing.

PMID- 8150133
TI  - So you want to treat TMJ?

PMID- 8150134
TI  - Median income outpaces inflation.

PMID- 8150135
TI  - Photos are valuable in designing this office.

PMID- 8150136
TI  - Tracking laboratory results.

PMID- 8150137
TI  - Could your management system falter?

PMID- 8150138
TI  - Achieving cosmetic and functional excellence with indirect resin inlays and
      onlays.

PMID- 8150139
TI  - Castable ceramic post/cores and crowns.

PMID- 8150140
TI  - Maxillary molar extractions and breakages.

PMID- 8150141
TI  - Aging and oral health: prevention isn't just for kids.

PMID- 8150142
TI  - Multidisciplinary approach to esthetic dentistry.

PMID- 8150143
TI  - Reattaching fractured tooth segments.

PMID- 8150144
TI  - Non-orthodontic correction of malpositioned and missing teeth.

PMID- 8150145
TI  - Infection-control training for the total staff.

PMID- 8150146
TI  - Intraoral cameras for everyone.

PMID- 8150147
TI  - When I grow up, I want to be a dentist.

PMID- 8150148
TI  - Responding to inquisitive patients.

PMID- 8150149
TI  - Dentistry by the boomers and for the boomers.

PMID- 8150150
TI  - Partnerships: the key ingredients.

PMID- 8150151
TI  - What is your practice worth?

PMID- 8150152
TI  - Smoking cessation: who is responsible?

PMID- 8150153
TI  - Staff salaries rise slowly.

PMID- 8150154
TI  - Paying for your child's education.

PMID- 8150155
TI  - Finally, answers to your questions about OSHA.

PMID- 8150156
TI  - A turning point in dentistry.

PMID- 8150157
TI  - Staff compensation takes big share of overhead pie.

PMID- 8150158
TI  - New year brings tax-law changes.

PMID- 8150159
TI  - Periodontics 2000.

PMID- 8150161
TI  - Intraoral cameras--are they for you?

PMID- 8150160
TI  - Incorporate high-tech equipment into your practice.

PMID- 8150162
TI  - An impression technique that will help you achieve clinical excellence.

PMID- 8150163
TI  - Orthodontic veneering and the cosmetic smile-lift.

PMID- 8150164
TI  - A step-by-step smile recovery.

PMID- 8150165
TI  - Snoring eliminated with simple dental appliance.

PMID- 8150166
TI  - Electronic anesthesia's role in dentistry's future.

PMID- 8150167
TI  - Negative media coverage will continue.

PMID- 8150168
TI  - A philosophy of risk management.

PMID- 8150169
TI  - Economic freedom.

PMID- 8150170
TI  - Are dental lasers for real?

PMID- 8150171
TI  - Scaling down.

PMID- 8150172
TI  - The hiring process: do it right the first time.

PMID- 8150173
TI  - Mutual funds: getting through the quicksand.

PMID- 8150174
TI  - One simple change.

PMID- 8150175
TI  - The ethics of dental practice sales.

PMID- 8150176
TI  - Management of dental trauma using bonded adhesive material.

PMID- 8150177
TI  - Faster, easier, better root planing with ultrasonics.

PMID- 8150178
TI  - Is managed care the answer?

PMID- 8150179
TI  - My early-morning business lesson.

PMID- 8150180
TI  - Purchasing a practice.

PMID- 8150182
TI  - How to increase referrals.

PMID- 8150181
TI  - Overhead control.

PMID- 8150183
TI  - Have you ever been sued?

PMID- 8150184
TI  - Maximize your recall system.

PMID- 8150185
TI  - Update on bleaching.

PMID- 8150186
TI  - Environmental considerations.

PMID- 8150187
TI  - To seal or not to seal.

PMID- 8150189
TI  - Immediately-placed implants after tooth extraction: a viable treatment option.

PMID- 8150188
TI  - Management of root lesions.

PMID- 8150190
TI  - Multiphase gutta-percha obturation technique.

PMID- 8150191
TI  - Would you choose dentistry again?

PMID- 8150192
TI  - The sun, the ozone layer and the skin: the role of ultraviolet light in lip and
      skin cancer.

PMID- 8150194
TI  - Root resorption: aetiology, classification and clinical management.

PMID- 8150193
TI  - The great eights debate: do the mandibular third molars affect incisor crowding?
      A review of the literature.

PMID- 8150196
TI  - Dose limitation in dental radiography.

PMID- 8150195
TI  - Amelogenesis imperfecta: a method of reconstruction.

PMID- 8150197
TI  - Exodontia and minor oral surgery for the child patient.

PMID- 8150198
TI  - Skeletal pattern is specified autonomously by the primary mesenchyme cells in sea
      urchin embryos.
AB  - In the sea urchin embryo the primary mesenchyme cells (PMCs) produce a CaCO3
      skeleton in a pattern that is species specific. To establish whether skeletal
      pattern is specified autonomously by the PMCs or through instructive interactions
      with the ectoderm, we have taken advantage of improvements in cell
      transplantation techniques to produce PMC/ectoderm chimeras between two species.
      It was found that the pattern of the skeletons produced in these chimeric embryos
      depended upon the source of the PMCs. Thus, skeletal pattern appears to be
      specified autonomously by the PMCs. In comparing this data with other information
      known about skeletogenesis, it is proposed that the ectoderm provides spatial and
      temporal information for the correct placement and timing of skeletogenesis, and
      that the PMCs then synthesize the skeleton according to an endogenous program.
      The ability of PMCs from one species to produce an appropriately patterned
      skeleton in the ectoderm of another indicates that the cues provided by the
      ectoderm are largely conserved between species.

PMID- 8150199
TI  - During fetal muscle development, clones of cells contribute to both primary and
      secondary fibers.
AB  - All mammalian muscle fibers are formed by cell fusion, but fiber formation occurs
      in two successive waves. Initially a small number of large fibers (primaries) are
      produced and are used as a scaffold for the formation of a larger number of
      smaller later forming fibers (secondaries). It has been reported that different
      populations of myoblasts are present at different ages, but it is unclear whether
      separate populations of cells contribute to primary and secondary fibers during
      the period of fetal development. We have tested this by injecting two replication
      deficient retroviruses, carrying a marker gene (lacZ), into the hind limbs of
      Embryonic Day (E) 15 and E17 mouse fetuses. All fetuses were killed at E19.
      Clusters of marked fibers (assumed to correspond to single clones) found after
      injection at both ages contained both primary and secondary fibers. This
      indicates that at these ages, a single population of cells contributes to both
      primary and secondary fibers.

PMID- 8150200
TI  - Isolation and characterization of a novel gene of the DEAD box protein family
      which is specifically expressed in germ cells of Xenopus laevis.
AB  - We have isolated a cDNA of the DEAD protein family from a Xenopus ovary cDNA
      library. Northern hybridization revealed that the mRNA corresponding to the cDNA
      [XVLG1 (Xenopus vasa-like gene)] was specifically expressed in adult testis and
      ovary. The deduced amino acid sequence of XVLG1 was relatively homologous to that
      of Drosophila vasa. XVLG1 protein was found to be expressed exclusively in adult
      testis and ovary by immunoblotting with a monoclonal antibody against XVLG1
      protein. Immunocytological study showed that XVLG1 protein was expressed in
      oogonia, oocytes, spermatogonia, spermatocytes, and also in primordial germ cells
      in stage 46 tadpoles. The monoclonal antibody used in this study specifically
      stains germ line cells and is useful both as a germ cell lineage marker and in
      biochemical studies of germ cells.

PMID- 8150201
TI  - Cell lineage of the prototroch of Patella vulgata (Gastropoda, Mollusca).
AB  - The trochophore larva of the archaeogastropod mollusc Patella vulgata has a well
      developed locomotory organ, the ciliated prototroch. This structure is formed
      from specific founder cells, the trochoblasts. Two methods were employed to
      determine the composition and cell lineage of the prototroch. Fluorescent cell
      lineage tracer injection in trochoblasts and trochoblast founder cells was used
      to show how the various trochoblasts became incorporated into the prototroch.
      Scanning electron microscopy was used to study both differentiation, more
      specifically ciliation, of trochoblasts and localization of trochoblasts in the
      prototroch. The results obtained with both methods are in accordance with each
      other. During early development all trochoblasts involved in prototroch formation
      become cell cycle-arrested and develop cilia. Subsequently, the trochoblasts
      shift in position to form a circular prototroch and a number of trochoblasts
      deciliate. As a result of these processes the mature prototroch consists of a
      number of heavily ciliated cells as well as a number of deciliated cells.
      Comparison of prototrochs from a number of spiralian species shows that this
      structure is very conserved during evolution. The significance of this is
      discussed.

PMID- 8150202
TI  - Plasticity in the development of topographic order in the mammalian
      retinocollicular projection.
AB  - The topographically ordered retinocollicular projection in rats emerges from an
      initially diffuse projection present in neonates through the elimination of
      aberrantly positioned axons and arbors. We explore developmental plasticity in
      this process by making partial retinal lesions at birth and determining the
      topographic mapping of the remaining retina at later ages when the map normally
      has a mature, retinotopic order. In normal mature rats, DiI focally injected into
      the retina labels axons that form a dense focus of overlapping arbors at the
      topographically correct location in the superior colliculus (SC). Similar
      injections in rats with partial retinal lesions label axons that form two
      discrete foci of arborizations; one at the topographically appropriate region of
      the SC and another in the region of the SC deprived of its normal retinal input
      by the retinal lesion. A focal injection of DiI into the "deprived" SC region
      retrogradely labels ganglion cells widely scattered in the retina. Therefore, a
      partial retinal lesion in developing rats does not lead to an orderly expansion
      of the remaining retinal projection to cover the entire SC, as it does in
      amphibians and fish following optic nerve regeneration. Rather, in rats, the
      remaining partial retina forms two distinct, contiguous projections to the SC: a
      retinotopically ordered one that retains normal topographic relationships and an
      aberrant, diffusely ordered one to the SC region topographically matched with the
      lesioned part of the retina. This abnormal persistence of topographically
      aberrant axons and arbors indicates that competitive interactions between retinal
      axons drive the remodeling of the initially diffuse retino-collicular projection
      into a topographically ordered one.

PMID- 8150203
TI  - Effects of localized application of retinoic acid on Xenopus laevis development.
AB  - In order to more accurately determine the mechanism by which retinoic acid causes
      embryonic defects, we have developed a simple method of locally applying retinoic
      acid rather than immersing the whole embryo in retinoic acid solutions. Retinoic
      acid was suspended in corn oil and then injected between the surface and the deep
      ectodermal layers of an early gastrula Xenopus embryo. When droplets containing
      retinoic acid were injected into the presumptive head region, the embryos
      exhibited inhibited development of anterior structures near the injection site.
      Development of the eye, cement gland, hatching gland, olfactory pits, and
      expression of engrailed protein were all disrupted near the injection site.
      Inhibited development of anterior structures was far greater on the injected side
      of the embryo than on the uninjected side. The retinoic acid droplet did not
      cause an anterior shift of structures on the injected side relative to the
      uninjected side. These experiments suggest that retinoic acid does not cause
      global respecification of axial level in the head, but rather suppresses
      development of anterior structures. Retinoic acid injected into presumptive trunk
      regions had no discernible effect.

PMID- 8150204
TI  - Expression of three mouse homologs of the Drosophila segment polarity gene
      cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm- and mesoderm-derived
      tissues suggests multiple roles during postimplantation development.
AB  - Three mouse genes, Gli, Gli-2, and Gli-3, which share a similar zinc finger
      domain with the products of the Drosophila segment polarity gene cubitus
      interruptus and the Caenorhabditis elegans sex-determining gene tra-1 were cloned
      and characterized. The expression patterns during postimplantation development of
      the three genes were analyzed by Northern blot, whole-mount, and section in situ
      hybridizations. Expression was first detected during gastrulation in both the
      ectoderm and mesoderm. Later in development, their expression became more
      restricted in various ectoderm- and mesoderm-derived tissues and was not
      detectable after completion of organogenesis. Interestingly, in the developing
      neural tube, Gli showed a narrow ventral domain of expression, whereas Gli-2 and
      Gli-3 showed a broad and dorsally restricted domain. Expression of these three
      Gli genes in various ectoderm- and mesoderm-derived tissues suggests that they
      play multiple roles during postimplantation development. Consistent with this
      hypothesis, a naturally occurring Gli-3 mutation, the mouse extra-toes mutant;
      shows defects in both mesoderm- and ectoderm-derived tissues.

PMID- 8150205
TI  - The Drosophila hydei gene Dhmst101(1) encodes a testis-specific, repetitive,
      axoneme-associated protein with differential abundance in Y chromosomal deletion
      mutant flies.
AB  - To understand the effect of the megabase-sized, Y chromosomal fertility genes on
      different stages of spermatogenesis in Drosophila hydei, an immunoscreening was
      performed to search for testis-specific protein-encoding cDNAs. The array of
      isolated clones contained cDNA sequences derived from a gene on chromosome 5 at
      101BC. The gene, Dhmst101(1), is a member of a small gene family and is
      specifically expressed in adult testis tissue. The mRNA encodes a protein of 344
      amino acids with a deduced apparent molecular weight of 37,793 Da. The main
      portion of the protein sequence comprises repetitive, highly charged amino acid
      units and shows repeat number variations among several D. hydei laboratory
      stocks. Immunocytochemistry with antibodies raised against synthetic peptides
      localized the protein product in elongated spermatids. This pattern of expression
      and the evaluation of biophysical considerations on the protein sequence data
      suggest that the Dhmst101(1) gene product may have some importance for the
      structural integrity of the sperm tail. Moreover, Y chromosomal deletions
      affecting correct spermiogenesis lead to degradation of the Dhmst101(1) gene
      product.

PMID- 8150206
TI  - Intermittent expression of BmFTZ-F1, a member of the nuclear hormone receptor
      superfamily during development of the silkworm Bombyx mori.
AB  - BmFTZ-F1 is a sequence-specific DNA-binding factor in the silkworm Bombyx mori
      sharing similar biochemical characteristics with Drosophila FTZ-F1, a member of
      the nuclear hormone receptor superfamily. Using DNA sequence homology with FTZ-F1
      and information on tryptic peptide sequences of BmFTZ-F1, we isolated a cDNA
      encoding for BmFTZ-F1. Amino acid sequences in the zinc finger DNA-binding region
      and the putative ligand-binding domain of BmFTZ-F1 showed strong similarity to
      not only FTZ-F1 but also its mammalian homologues, LRH-1, ELP, and Ad4BP,
      suggesting the importance of each region for the function of these proteins.
      Northern blot analyses of RNA isolated from the middle and posterior silk glands
      and fat bodies showed that a 6.1-kb BmFTZ-F1 mRNA is present in all tissues so
      far examined. Expression of BmFTZ-F1 mRNA is intermittent, being high during
      larval molting and both the larval-pupal and the pupal-adult transformations.
      Injection of 20-hydroxyecdysone at the third day of the 5th instar larvae induced
      BmFTZ-F1 mRNA in the posterior silk gland after 24 hr. When 5th instar silk
      glands were cultured in vitro, BmFTZ-F1 mRNA was induced by a 6-hr exposure to 20
      hydroxyecdysone followed by 6 hr in hormone-free medium. These results suggest
      that BmFTZ-F1 is inducible by decline in the ecdysteroid titer and may play an
      important role in the development of the silkworm as a transcription factor.

PMID- 8150207
TI  - Neural crest cell interactions with laminin: structural requirements and
      localization of the binding site for alpha 1 beta 1 integrin.
AB  - We have identified the sites of neural crest cell interaction with laminin in
      vitro by examining their ability to attach to and migrate on proteolytic
      fragments of the molecule and the ability of fragment-specific antibodies to
      inhibit these interactions. The binding site on laminin was localized to the E8
      domain on the long arm of laminin, as well as the T8' fragment within this
      domain, but not the E1', E3, or E4 fragments. Only subfragments containing the
      carboxy-terminal rod-like portion of the A chain plus the corresponding B1 and B2
      chains retained the attachment-promoting activity of the parent E8 fragment. In
      addition, interactions required maintenance of the triple-stranded and alpha
      helical coiled-coil structure of this domain. Reduction and alkylation of laminin
      and the E8 and T8 fragments significantly reduced neural crest cell attachment
      and migration. An antiserum against chick alpha 1 integrin reduced migration and
      adhesion of neural crest cells on an intact laminin-nidogen complex, the E8
      fragment, and all its active subfragments. Furthermore, we observed that neural
      crest cells modified laminin substrata prepared in the absence of divalent
      cations. Early stable attachment to these substrata was mediated by an integrin
      other than alpha 1, whereas later attachment and migration were mediated by alpha
      1 integrins. Our results suggest that neural crest cells selectively bind to the
      B1-A-B2 mid-portion (T8') of the E8 domain of laminin, requiring structural
      integrity of this region and that they modify laminin substrata as a result of
      prolonged cell-matrix interactions.

PMID- 8150208
TI  - Two Drosophila regulatory genes, deformed and the Broad-Complex, share common
      functions in development of adult CNS, head, and salivary glands.
AB  - Deformed (Dfd), a homeotic selector gene required for segment identity in the
      head, and the Broad-Complex (BR-C), a steroid hormone-regulated locus required
      for metamorphosis of the epidermis and multiple internal tissues, are members of
      distinct genetic regulatory hierarchies. Their protein products contain DNA
      binding domains (of the homeodomain and zinc-finger variety, respectively) and
      are believed to act by regulating the transcription of target genes. In this
      study we demonstrate that Dfd and BR-C mutants dying during metamorphosis share
      defects of CNS reorganization, ventral adult head development, and adult salivary
      gland morphogenesis. Specifically, the shared phenotypes are (i) failure to
      separate the subesophageal ganglion (SEG) from the thoracic ganglion (TG); (ii)
      structural and functional abnormalities of the proboscis and maxillary palps,
      innervated by the SEG; and (iii) failure of the adult salivary glands to extend
      into the thorax. Experiments performed with a conditional allele demonstrate that
      Dfd+ function during either larval life or metamorphosis is sufficient to rescue
      the SEG-TG separation phenotype. BR-C;Dfd double mutants show synergistic
      enhancement of the ventral head defects. This genetic interaction suggests that
      the segment identity and steroid hormone-sensitive regulatory hierarchies
      intersect during postembryonic development.

PMID- 8150209
TI  - Myogenic cell lines derived from transgenic mice carrying a thermolabile T
      antigen: a model system for the derivation of tissue-specific and mutation
      specific cell lines.
AB  - Skeletal myoblasts cloned from limb muscles of H-2Kb-tsA58 transgenic mice
      remained proliferative through at least 80 generations under conditions
      permissive for expression and function of the tsA58 gene product. When switched
      to nonpermissive conditions or implanted into muscles of nude mdx mice they
      underwent differentiation but, in one clonal cell line, a small proportion
      appeared to become quiescent muscle precursors in vivo. H-2Kb-tsA58 X mdx/mdx F1
      male mice yielded dystrophin-deficient myoblasts. By such simple genetic crosses,
      H-2Kb-tsA58 transgenic mice provide a valuable tool for the rapid isolation of
      cell lines, myogenic or otherwise, bearing mutations of interest.

PMID- 8150210
TI  - Inhibition of protein and lipid sulfation in oligodendrocytes blocks biological
      responses to FGF-2 and retards cytoarchitectural maturation, but not
      developmental lineage progression.
AB  - We have examined the interfaces between protein and lipid sulfation, the response
      of progenitor cells to specific growth factors, and developmental lineage
      progression. The experimental system used is the oligodendrocyte (OL), the cell
      responsible for myelination of axons in the central nervous system. The ability
      to regulate the growth and differentiation of oligodendrocytes in primary
      cultures growing in defined medium offers a particularly attractive model for
      these interrelated areas of cell and developmental biology. Sulfation was
      inhibited in this system by growing cells in sodium chlorate, a competitive
      inhibitor of sulfation. Four principal conclusions are drawn from the data.
      First, heparan sulfate proteoglycan is a necessary cofactor for the environmental
      regulation by FGF-2 of nontransformed oligodendrocyte progenitors, including both
      the mitogenic response and the inhibition of terminal differentiation at a
      specific stage of the lineage. Second, the differentiation of oligodendrocyte
      progenitors from an early to a mature stage can occur in the absence of
      sulfation. Third, however, the formation of cellular processes and myelin-like
      sheets is retarded, leading to the prediction that sulfated molecules are
      critically involved in aspects of oligodendrocyte differentiation directly
      relating to myelination per se. Fourth, the developmental proligodendroblast
      antigen, POA, is a sulfated molecule. The results provide clear evidence for the
      importance of sulfation for the responses of OL progenitors to FGF-2 and for OL
      cytoarchitectural maturation, while demonstrating an ability of OL progenitors to
      undergo lineage progression in its absence.

PMID- 8150211
TI  - Measurement of time in oligodendrocyte-type-2 astrocyte (O-2A) progenitors is a
      cellular process distinct from differentiation or division.
AB  - When stimulated by platelet-derived growth factor (PDGF), oligodendrocyte-type-2
      astrocyte (O-2A) progenitors derived from perinatal rat optic nerves undergo a
      limited number of cell divisions before clonally related cells synchronously and
      symmetrically differentiate into nondividing oligodendrocytes. The duration of
      this mitotic period is thought to be controlled by a cell-intrinsic biological
      clock. Thus, in the presence of PDGF, the measurement of time by the biological
      clock is intimately coupled to the control of division and differentiation. In
      contrast, O-2A progenitors grown in the presence of PDGF plus basic fibroblast
      growth factor (bFGF) divide indefinitely in the absence of differentiation and so
      do not exhibit a limited period of division. We have tested whether growth in
      PDGF plus bFGF alters the duration of the limited period of division O-2A
      progenitors exhibit in response to PDGF alone. Accordingly, O-2A progenitors were
      grown in the presence of PDGF plus bFGF for varying lengths of time, before being
      switched to conditions that promote timed differentiation (PDGF but not bFGF).
      Increasing duration of culture in PDGF plus bFGF led to a gradual shortening of
      the period for which O-2A progenitors were subsequently responsive to PDGF alone,
      until eventually all cells differentiated without dividing after switching. In
      contrast, a short exposure to bFGF was not sufficient to cause a similar
      alteration in the pattern of differentiation. These results indicate that O-2A
      progenitors prevented from undergoing timed differentiation nevertheless retain
      the ability to measure elapsed time, implying that the biological clock in this
      cell type can be uncoupled from differentiation. Furthermore, they demonstrate
      that the biological clock does not impose an absolute limit on the number of
      divisions that an O-2A progenitor can undergo. In contrast with existing
      hypotheses, our observations suggest that the molecular mechanism that controls
      timed differentiation must consist of at least two components, with the clock
      itself being in some manner distinct from mechanisms that limit cell division
      and/or directly regulate differentiation.

PMID- 8150212
TI  - Electrical activity in the neuromuscular unit can influence the molecular
      development of motor neurons.
AB  - During the first few weeks of postnatal life spinal motor neurons develop
      electrophysiological, morphological, and molecular features that are
      characteristic of adult motor neurons. To understand how the acquisition of the
      mature neuronal phenotype is regulated, we have examined the expression of the
      motor neuron cell surface proteoglycan recognized by monoclonal antibody Cat-301
      in the hamster. Previously we found that Cat-301 immunoreactivity is not present
      on motor neurons at birth and that by the end of the second postnatal week all
      motor neurons are Cat-301-positive. Surgical and pharmacological lesion studies
      have shown that the onset of Cat-301 expression depends upon input from both
      large-diameter primary afferents and from supraspinal afferents. Once the Cat-301
      proteoglycan is expressed on motor neurons, its continued expression is
      independent of these inputs. These studies suggested that motor neuron maturation
      depends upon the coordination of several afferent inputs during the first
      postnatal weeks of life. Our previous studies could not address whether segmental
      and descending afferents (i) provide a chemical signal (such as a trophic factor)
      or (ii) confer a pattern of neuronal activity upon motor neurons that then
      results in the expression of the Cat-301 proteoglycan. The present experiments
      examine the role of electrical activity in motor neuron maturation. In normal
      animals, all sciatic motor neurons are Cat-301-positive by Postnatal Day 19
      (P19). Chronic application of the sodium channel blocker, tetrodotoxin (TTX), to
      the sciatic nerve in neonatal animals reduces the percentage of Cat-301-positive
      motor neurons found at P21 by one-third. This reduction is not due to a
      nonspecific inhibition of all protein synthesis, because the expression of two
      other motor neuron antigens proceeds normally in TTX-treated neonates. Blockade
      of neuromuscular transmission in neonates by Botulinus toxin A also reduces the
      percentage of Cat-301-positive motor neurons. Cat-301 expression is not tied
      simply to neuronal activity, because chronic application of TTX to the sciatic
      nerve, or Botulinus toxin A to muscles, in the adult does not reduce Cat-301
      expression. These findings indicate that electrical activity generated within the
      neuromuscular unit in early postnatal life can influence the acquisition of
      mature molecular properties by motor neurons.

PMID- 8150213
TI  - Adult forms of nicotinic acetylcholine receptors are expressed in the absence of
      nerve during differentiation of a mouse skeletal muscle cell line.
AB  - Changes in the functional properties of acetylcholine receptor (AchR) channels
      were followed in the C2 muscle cell line over the period of 1 to 17 days
      following myotube formation. Up to 1 week after myotube formation, the
      predominant class of channel exhibited low (45 pS) conductance and long mean
      channel open time (14 msec), characteristic of the major type of AchR in
      embryonic skeletal muscle. Three additional Ach-activated currents with
      conductances lower than 45 pS and long channel open times were also observed.
      Seven to 10 days following myotube formation, channels of 45 pS and 65 pS and
      short (2-6 msec) mean open duration were observed, characteristic of receptor
      channels in adult muscle. Increases in epsilon subunit mRNA levels preceded the
      functional expression of channels with brief open durations. Our results show
      that C2 muscle cells maintained in culture express a full range of functionally
      distinct AchR types in the absence of nerve.

PMID- 8150214
TI  - Receptor subtype and intracellular signal transduction pathway associated with
      situs inversus induced by alpha 1 adrenergic stimulation in rat embryos.
AB  - In previous studies, we have demonstrated that stimulation of alpha 1 but not
      alpha 2 or beta adrenergic receptors in rat embryos grown in culture interferes
      with normal development of the left/right body axis leading to situs inversus. In
      the present study, we aimed to determine the alpha 1 adrenergic receptor subtype
      and signal transduction pathway involved in this phenomenon. Rat embryos at Stage
      11a by a modified Theiler's staging system were cultured for 50 hr in medium
      containing various compounds which are known to activate or inhibit different
      sites of the signal transduction pathways associated with alpha 1 adrenergic
      receptors. They were then examined to determine the sidedness of asymmetric body
      structures. WB4101, a selective antagonist of alpha 1A adrenergic receptor
      subtype, but not chlorethylclonidine, a selective antagonist of alpha 1B
      adrenergic receptor subtype, inhibited phenylephrine (an alpha 1 adrenergic
      agonist)-induced situs inversus. Neither the protein kinase C (PKC) activators
      phorbol 12-myristate 13-acetate and SC-9 nor the PKC inhibitor calphostin C
      caused situs inversus. Furthermore, calphostin C did not block phenylephrine
      induced situs inversus. A23187, a Ca2+ ionophore, induced situs inversus;
      nifedipine, a L-type Ca2+ channel blocker, partially blocked phenylephrine
      induced situs inversus. The calmodulin antagonists trifluoperazine, W-7, and W-13
      blocked phenylephrine-induced situs inversus, although they did not cause situs
      inversus by themselves. KN-62, a Ca2+/calmodulin-dependent protein kinase II (CaM
      kinase II) inhibitor, dose-dependently blocked phenylephrine-induced situs
      inversus. However, higher concentrations of this compound produced no block in
      the presence of phenylephrine and in its absence produced a 50% incidence of
      situs inversus. These results indicate that alpha 1 adrenergic stimulation
      induced situs inversus is mediated by the alpha 1A adrenergic receptor subtype
      and that activation of CaM kinase II but not PKC may be involved.

PMID- 8150215
TI  - In vitro development of the sea urchin male pronucleus.
AB  - We have developed a cell-free extract from fertilized or unfertilized sea urchin
      eggs which promotes formation of male pronuclei from exogenously added
      permeabilized sperm nuclei. Using a buffer to simulate egg cytoplasmic
      conditions, three states of nuclear condensation can be distinguished: condensed
      (conical), partially decondensed (conical or ovoid), and decondensed (spherical).
      The in vitro system meets several in vivo criteria established by microinjection
      experiments. Decondensation is promoted at elevated pH and in activated egg
      cytoplasm, but does not require Ca2+. Pronuclear development is supported to >
      100 male nuclei per egg-equivalents as in vivo. Pronuclear development requires
      addition of an ATP-generating system and is blocked by two kinase inhibitors (6
      DMAP and staurosporine) at the same concentrations effective in vivo. Decondensed
      nuclei form by 40 min of incubation and acquire a putative nuclear envelope shown
      by exclusion of 150 kDa FITC-dextran by 1-2 hr. The rates of decondensation and
      nuclear envelope formation are accelerated by addition of GTP. Protease
      inhibition experiments suggest a role for nonhistone protein degradation in
      pronuclear progression. This system should prove useful for investigating
      mechanisms of the postmeiotic sea urchin male chromatin remodeling which follows
      fertilization, previously accessible only in vivo.

PMID- 8150216
TI  - Cell-layer interactions influence the number and position of lateral shoot
      meristems in Nicotiana.
AB  - In higher plants the formation of lateral shoot meristems (i.e., axillary
      meristems) in the axils of leaves establishes potential growth centers along the
      principal axis of the stem. The position and number of lateral buds in Nicotiana
      glauca, two genotypes of Nicotiana tabacum, and a series of interspecific
      periclinal chimeras composed of these species was studied to establish the role
      of position (location of the node along the main axis), flowering, and cell-layer
      interactions on the pattern of lateral meristem initiation. In N. glauca, both
      the number of nodes generated and the transition to flowering influenced the
      number and position of lateral meristems. A short-day mutant of N. tabacum grown
      under long days remained vegetative and never produced multiple lateral buds per
      node, indicating that attaining a certain node number was not sufficient to cause
      the formation of multiple buds. Yet, flowering plants of both short-day and day
      neutral N. tabacum possessed multiple buds in their upper nodes. An analysis of
      the number of buds per node and bud position along the main axis in periclinal
      chimeras indicated that the genotype of the third apical layer (LIII) of the
      meristem had the greatest influence on the pattern of lateral shoot meristems in
      both vegetative and flowering plants. The lineage of the three apical layers (LI,
      LII, and LIII) of the terminal shoot meristem was preserved in primary (1 degree)
      lateral meristems but minor deviations in lineage were observed in secondary (2
      degrees) buds (i.e., those formed later but in the same node as the 1 degree
      bud). An analysis of the phenotype of 2 degrees shoots that displayed deviations
      from expected lineage indicated that in most cases the periclinal cell divisions
      that destabilized the lineage occurred at the flanks of the meristem and began
      before the most basal node, indicating that periclinal cell divisions most likely
      occurred prior to the inception of the 2 degrees lateral meristem. Based on our
      studies, we conclude that both 1 degree and 2 degrees lateral meristems in
      Nicotiana ultimately descend from derivatives of all three apical layers of the
      terminal shoot meristem.

PMID- 8150217
TI  - Evidence for both tyrosine kinase and G-protein-coupled pathways leading to
      starfish egg activation.
AB  - To investigate possible pathways leading to egg activation at fertilization, the
      ability of exogenously introduced tyrosine kinase and G-protein-coupled receptors
      to mimic events of fertilization was examined. Oocytes of the starfish Asterina
      miniata were injected with RNA for a chimeric receptor consisting of the
      extracellular domain of the beta form of the mouse platelet-derived growth factor
      (PDGF) receptor and the transmembrane/intracellular domain of the human
      fibroblast growth factor (FGF) receptor, or with RNA for the rat serotonin 1c
      receptor. These oocytes were cultured for 1 to 3 days and then matured with 1
      methyladenine. In response to PDGF or serotonin, the injected eggs underwent
      responses like those at fertilization: cortical granule exocytosis, a rise in
      intracellular free calcium, and DNA synthesis. Some of these artificially
      activated eggs cleaved, and some of the PDGF-activated eggs were observed to form
      larvae. A PDGF/FGF receptor with a point mutation which eliminated its ability to
      interact with phospholipase C-gamma did not cause fertilization-like responses.
      Thus components of a signaling pathway involving phospholipase C-gamma,
      characteristic of tyrosine kinase receptors, as well as components of a pathway
      involving a G-protein and phospholipase C-beta, characteristic of G-protein
      coupled receptors, appear to be present in starfish eggs. Either or both could
      function in egg activation at fertilization.

PMID- 8150218
TI  - Speract receptors are localized on sea urchin sperm flagella using a fluorescent
      peptide analog.
AB  - In two species of sea urchins, Strongylocentrotus purpuratus and Lytechinus
      pictus, the egg jelly-associated decapeptide, speract, binds to specific sperm
      surface receptors resulting in increased sperm motility and respiration rate.
      Previously, a peptide analog, GGG[Y2]-speract, was used to identify a 77-kDa
      receptor on intact sperm cells using chemical cross-linking. In this paper we
      describe the synthesis and characterization of a fluorescent derivative of
      GGG[Y2]-speract for use as a probe for the sperm receptor. Fluorescein
      isothiocyanate (FITC) was conjugated to the amino terminus of GGG[Y2]-speract and
      the resulting analog (FITC-GGG[Y2]-speract) was purified by size exclusion
      chromatography and reverse-phase HPLC. Competition binding studies with the
      fluorescent peptide and intact spermatozoa yielded IC50 values which were
      indistinguishable from native speract and GGG[Y2]-speract (approximately 20 nM).
      FITC-GGG[Y2]-speract half-maximally stimulated sperm respiration at a
      concentration nearly identical to that of the native peptide (EC50 approximately
      50 pM). Using digitally enhanced video imaging fluorescence microscopy, FITC
      GGG[Y2]-speract was used to localize the speract receptor on the flagella of
      intact sperm. Excess concentrations of both unlabeled speract and GGG[Y2]-speract
      abolished the binding of the fluorescent analog, yet unrelated peptides did not.
      Further, results of cross-linking experiments using 125I-GGG[Y2]-speract and
      purified sperm flagella and heads were consistent with the fluorescent labeling
      results on whole cells. The finding that the speract receptor is localized
      exclusively to the sperm flagella may reveal its role in the regulation of
      flagellar motility.

PMID- 8150219
TI  - Retinoic acid gradients during limb regeneration.
AB  - Retinoids have been implicated in pattern formation processes in both developing
      chick limbs and in the regenerating limbs of urodele amphibians as well as in
      other aspects of embryonic development. Since chick wing buds have been shown to
      have a higher concentration of all-trans-retinoic acid (RA) in the posterior
      region than in the anterior region, we set out to look for a gradient of RA in
      the regenerating limb of the axolotl, Ambystoma mexicanum. We used high
      performance liquid chromatography to separate, identify, and measure the
      concentration of retinoids present in the tissues. Our results show that the
      concentration of RA is about five times higher in posterior quarters of the limb
      regeneration blastema compared to anterior quarters. In addition, levels of RA
      are about two and a half times higher in blastemas from the radius-ulna level of
      the limb compared to those from the humerus level. By contrast, the limb
      regenerates of the African clawed frog, Xenopus laevis (which produce a
      regenerative outgrowth which is pattern-deficient), do not exhibit an
      anteroposterior gradient of any of the retinoids investigated. This paper also
      reports on the levels of retinoids in a number of other tissues as well. This
      anteroposterior gradient of RA in the axolotl limb regeneration blastema has
      significant implications for pattern formation during limb development and
      regeneration.

PMID- 8150220
TI  - Isolation and partial characterization of a gene from trachea of Manduca sexta
      that requires and is negatively regulated by ecdysteroids.
AB  - The molting cycle in insects is regulated by the fluctuating levels of
      ecdysteroids. Twenty-four hours prior to the pupal molt in Manduca sexta steroid
      titers are relatively high and they fall to very low levels at 4 hr before the
      molt. Several physiological events accompanying molts have been shown to require
      the rise and then the subsequent decline of ecdysteroid levels. These events also
      require the expression of a new set of genes. We used subtractive hybridization
      to isolate genes that are expressed 4 hr, but not 24 hr, prior to the pupal molt
      in the nervous system of Manduca. These genes are expected to play a role either
      in ecdysis behavior or in the development of pupal/adult structures. The first
      such gene we have identified, esr20 (EcdySteroid Regulated) encodes a 20-kDa
      protein. The deduced amino acid sequence of the protein shows similarity to
      acidic domains in three urelated proteins, chick nucleolin, rat heavy-molecular
      weight neurofilament, and the Drosophila steroid orphan receptor, knirps-related.
      The similarity among the four proteins appears to be in regions implicated in
      protein-protein interactions. The accumulation of esr20 mRNA starts 16 hr prior
      to the pupal molt and abruptly stops at ecdysis. Expression of esr20 was
      localized to tracheal epithelial cells within all tissue types, and the
      transcript was present prior to the larval, pupal, and adult molts only after the
      molting peak of ecdysteroids had declined. Its expression was inhibited in the
      presence of ecdysteroids in vitro and required protein synthesis.

PMID- 8150221
TI  - Aminoguanidine reduces regional albumin clearance but not urinary albumin
      excretion in streptozotocin-diabetic rats.
AB  - Advanced glycation end-product-formation is thought to play a role in the
      development of diabetic angiopathy. By altering the structure of different
      extracellular matrix components advanced glycation end-products might affect
      vascular and glomerular permeability. In this study we investigated the effect of
      treatment with an inhibitor of advanced glycation end-product-formation,
      aminoguanidine, on vascular permeability and the development of albuminuria in
      streptozotocin-induced diabetic rats. Male Wistar Rp rats were randomized into a
      control group, a diabetic group, and an aminoguanidine-treated diabetic group.
      After 8 weeks, 24-h urine collections were taken and rats were implanted with an
      arterial and a venous catheter. mean arterial blood pressure was determined by
      intra-arterial measurement. Regional albumin clearances were assessed in the eye,
      ileum, lung, skeletal muscle and skin using an isotope technique. Mean arterial
      pressure in the diabetic group was significantly lower in the control and
      aminoguanidine-treated groups (p < 0.02). Regional albumin clearances were
      significantly increased in all tissues of diabetic rats compared to control rats
      (p < 0.05). Aminoguanidine treatment of diabetic rats resulted in a significant
      decrease of regional albumin clearance in all tissues except the lung (p < 0.05,
      lung p = 0.07). The development of albuminuria in diabetic rats however, was not
      affected by aminoguanidine.

PMID- 8150223
TI  - Impact of donor-related variables on islet isolation outcome in dogs.
AB  - Clinical human islet transplantation programmes are considerably hampered by the
      variability of islet isolation outcome. The effects of the islet content of the
      pancreas and other donor-related variables on isolation outcome have not been
      evaluated systematically so far--either in large animals, or in man. We studied
      the impact of interindividual differences in age, body weight and pancreatic
      islet content on the outcome of collagenase isolation of islets from the splenic
      pancreas of beagle dogs (n = 31). The islet volume of the splenic pancreas
      amounted to a mean (+/- SEM) 15.7 +/- 0.9 microliters per gramme pancreas, and
      varied three-fold (from 8.4 to 27.3 microliters). Isolated islet yield was 7.6 +/
      0.7 microliters/g and varied nine-fold (1.8-16.3 microliters). Animals also
      varied in age eight-fold (8-67 months) and body weight two-fold (8.6-18.3 kg).
      Differences in body weight and age explained 60% of variance in the fractional
      islet volume of the pancreas and 50% of the variance in islet yield (p < 0.001).
      Fractional islet volume of the splenic pancreas also explained 50% of the
      variance in islet yield (p < 0.001). We conclude that the outcome of islet
      isolation may be predictable after controlling for the variable islet content of
      pancreases, and other donor-related variables, and suggest that similar studies
      should be done in man.

PMID- 8150222
TI  - Glucokinase gene in gestational diabetes mellitus: population association study
      and molecular scanning.
AB  - Mutations of the glucokinase gene result in early-onset familial Type 2 (non
      insulin-dependent) diabetes mellitus, and several members of the mutant
      glucokinase kindreds were originally diagnosed as having gestational diabetes.
      This study examined the glucokinase gene in 270 American Black women, including
      94 with gestational diabetes whose diabetes resolved after pregnancy (gestational
      diabetes only), 77 with gestational diabetes who developed Type 2 diabetes after
      pregnancy (overt diabetes), and 99 normal control subjects who were recruited
      during the peripartum period. Two simple sequence repeat polymorphisms flanking
      either end of the glucokinase gene were evaluated. No association was found
      between glucokinase alleles and gestational diabetes only or overt diabetes,
      after adjustment for multiple comparisons. To detect single base changes, all 11
      exons and proximal islet and liver promoter regions were examined by polymerase
      chain reaction plus single-stranded conformational polymorphism analysis in 45
      gestational diabetes only patients who had not yet developed Type 2 diabetes.
      Nine coding region variants were identified: Ala11 (GCC) to Thr11 (ACC) in islet
      exon 1, and 8 variants either in untranslated regions or in the third base of a
      codon. Four variant sites were found in introns, but none in splicing consensus
      sequences. Analysis of the promoter regions revealed two common variants, G-->A
      at islet -30 (24%), and G-->A at liver -258 (42%). The frequencies of the
      promoter variants, determined by allele specific polymerase chain reaction
      analysis, but did not differ among the three groups. Thus, no significant coding
      sequence glucokinase mutations were found in 90 alleles from 45 patients with
      gestational diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150224
TI  - Primary nitrate tolerance in diabetes mellitus.

PMID- 8150225
TI  - Reactive oxygen intermediates in autoimmune islet cell destruction of the NOD
      mouse induced by peritoneal exudate cells (rich in macrophages) but not T cells.
AB  - The non-obese diabetic (NOD) mouse spontaneously develops autoimmune Type 1
      (insulin-dependent) diabetes mellitus. NOD mice exhibit massive infiltrates of T
      cells and macrophages into pancreatic islets (insulitis) prior to diabetes. The
      contribution of oxygen free radicals to the development of insulitis in NOD mice
      was examined by administration of its scavengers, such as superoxide dismutase
      and catalase. Bovine superoxide dismutase and catalase were each coupled to
      polyethylene glycol. The treatment with superoxide dismutase-polyethylene glycol
      reduced the number of islets with insulitis and increased the undamaged islet
      tissue, as compared with the control group. The treatment with catalase
      polyethylene glycol showed a similar tendency which did not reach significance.
      Using a flow cytometric assay of the oxidation of 2', 7'-dichlorofluorescein, the
      content of reactive oxygen intermediates in islet cells in the culture system was
      measured and the effect of peritoneal exudate cells and T cells on their
      production examined. Peritoneal exudate cells, but not T cells, from NOD mice
      increased the content of reactive oxygen intermediates in islet cells of either
      the NOD mouse or the ILI mouse (MHC-identical to NOD); the addition of superoxide
      dismutase to the culture medium suppressed this increase in NOD or ILI islet
      cells. The present data support the concept that production of oxygen free
      radicals mediated by macrophages can damage islet beta cells, directly resulting
      in autoimmune Type 1 diabetes in NOD mice.

PMID- 8150226
TI  - Insulin-induced translocation of GLUT 4 in skeletal muscle of insulin-resistant
      Zucker rats.
AB  - The genetically obese Zucker rat (fa/fa) is an animal model with severe insulin
      resistance of the skeletal muscle. We investigated whether a defect of insulin
      dependent glucose transporter (GLUT 4) translocation might contribute to the
      pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as
      well as normal Wistar rats were injected intraperitoneally with insulin and were
      killed after 2 or 20 min, respectively. Subcellular fractions were prepared from
      hind-limb skeletal muscle and were characterized by determination of marker
      enzyme activities and immunoblotting applying antibodies against alpha 1 Na+/K+
      ATPase. The relative amounts of GLUT 1 and GLUT 4 were determined in the
      fractions by immunoblotting with the respective antibodies. Insulin induced an
      approximately two-fold increase of GLUT 4 in a plasma membrane and transverse
      tubule enriched fraction and a decrease in the low density enriched membrane
      fraction in all three groups of rats. There was a high individual variation in
      GLUT 4 translocation efficiency within the groups. However, no statistically
      significant difference was noted between the groups. No effect of insulin was
      detectable on the distribution of GLUT 1 or alpha 1 Na+K+ ATPase. The data
      suggest that skeletal muscle insulin resistance of obese Zucker rats is not
      associated with a lack of GLUT 4 translocation.

PMID- 8150227
TI  - Aminoguanidine inhibits the development of accelerated diabetic retinopathy in
      the spontaneous hypertensive rat.
AB  - Arterial hypertension has been identified as a major secondary risk factor for
      diabetic retinopathy. However, the mechanisms by which hypertension worsens
      retinopathy are unknown. Inhibition of advanced glycation product formation
      prevents the development of experimental diabetic retinopathy in normotensive
      diabetic rats. In this study the effect of hypertension on the rate of diabetic
      retinopathy development and the formation of arteriolar thrombosis was evaluated.
      We also evaluated the effect of aminoguanidine, an inhibitor of advanced
      glycation and product formation on retinal pathology of diabetic hypertensive
      rats. After 26 weeks of diabetes, hypertension accelerated the development of
      retinopathy despite a lower mean blood glucose level than in the non-hypertensive
      group (diabetic spontaneous hypertensive rats (SHR) 16.00 +/- 6.83 mmol/l;
      diabetic normotensive Wistar Kyoto rats (WKY) 34.9 +/- 3.64 mmol/l; p < 0.0001).
      Diabetic SHR had nearly twice as many acellular capillaries as diabetic WKY (SHR
      diabetic: 91.9 +/- 7.5 acellular capillaries per mm2 of retinal area vs WKY
      diabetic: 53.7 +/- 8.5 acellular capillaries per mm2 of retinal area), and a 3.8
      fold increase in the number of arteriolar microthromboses (SHR diabetic 23,504 +/
      5523 microns2 vs SHR non-diabetic 6228 +/- 2707 microns2). Aminoguanidine
      treatment of SHR diabetic rats reduced the number of acellular capillaries by
      50%, and completely prevented both arteriolar deposition of PAS-positive material
      and abnormal microthrombus formation. These data suggest that hypertension
      induced deposition of glycated proteins in the retinal vasculature plays a
      central role in the acceleration of diabetic retinopathy by hypertension.

PMID- 8150228
TI  - Altered endothelin-1 induced contraction and second messenger generation in
      bovine retinal microvascular pericytes cultured in high glucose medium.
AB  - The effect of simulated hyperglycaemia on bovine retinal pericytes was studied
      following culture of these cells for 10 days under normal (5 mmol/l) and elevated
      (25 mmol/l) glucose conditions in the absence of endothelial cells. Pericytes
      cultured under high ambient glucose exhibited both a delayed and reduced
      contractile response following stimulation with endothelin-1. Stimulation with
      10(-7) mol/l endothelin-1 for 30 s caused significant contraction in cells grown
      in both 5 mmol/l and 25 mmol/l glucose. The former also contracted significantly
      with 10(-8) mol/l endothelin-1. Further, at all concentrations tested,
      statistical comparison of the time course of contraction showed a significant
      difference (p < 0.02) in the reduction of planimetric surface area between the
      two cell groups. Since neither binding of endothelin-1 nor the number of
      receptors for this peptide were significantly different (p > 0.1) between bovine
      retinal pericytes grown for 10 days under normo- or hyperglycaemic conditions, it
      became apparent that the altered contractility in bovine retinal pericytes
      following culture in high glucose must be due to post-binding intracellular
      disturbance(s). Indeed, both basal and 15 s post-stimulation with 10(-8) mol/l
      endothelin-1, levels of inositol trisphosphate were significantly reduced (p <
      0.05 and p < 0.02, respectively) in pericytes cultured for 10 days in 25 mmol/l
      glucose. These results show that endothelial-independent alterations in
      contractility of pericytes occur when they are grown in conditions which simulate
      hyperglycaemia. The results also suggest that the observed attenuation in
      response to endothelin-1 stimulation evident in pericytes grown under simulated
      hyperglycaemic conditions is not due to alterations in peptide binding.

PMID- 8150229
TI  - Nerve ischaemia in diabetic rats: time-course of development, effect of insulin
      treatment plus comparison of streptozotocin and BB models.
AB  - This study sought to determine the time-course of development of reduced nerve
      laser Doppler flux in experimental diabetes and the effect on this anomaly of
      insulin treatment. In addition, we aimed to compare nerve laser Doppler flux in
      streptozotocin- and genetically-diabetic BB rat models. Sciatic nerve laser
      Doppler flux in diabetic rats was variable during the 2 days following
      streptozotocin injection; from day 4, when the measurement was 80% of control,
      fluxes fell steadily and formed a plateau at 40% of control values after 4 weeks
      of diabetes. In a second study, using rats with 4-week streptozotocin-diabetes,
      sciatic nerve laser Doppler flux was reduced to 44% of the value measured in
      control rats. Treatment of a parallel group of diabetic rats with insulin, by
      sustained release implants, prevented this ischaemia, so that nerve laser Doppler
      flux was 91% of controls. Nerve Doppler flux in BB rats with 6-week genetic
      diabetes was 57% of a control (non-diabetic) BB group. There were no differences
      in mean arterial pressures between control and diabetic rats in any of the
      studies. Heart rates of control and insulin-treated diabetic animals were higher
      than those of the untreated diabetic group; in the other studies heart rates of
      diabetic animals were numerically lower than controls, but not significantly so.
      These observations suggest that sciatic nerves of rats with short-term diabetes,
      whether induced with streptozotocin or of genetic origin, are markedly ischaemic
      and that this ischaemia in streptozotocin-diabetes is evident within a week of
      diabetes onset, forms a plateau after 4 weeks and is maintained for at least 2
      months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150230
TI  - Betel nut (Areca catechu) consumption and the induction of glucose intolerance in
      adult CD1 mice and in their F1 and F2 offspring.
AB  - Many mutagenic nitroso compounds are also diabetogenic. Betel-nut (Areca catechu)
      chewing populations have an increased incidence of foregut cancers related to
      betel-nut nitrosamines which suggests that betel consumption could be
      diabetogenic. Young adult CD1 mice with a low spontaneous incidence of diabetes
      were fed betel nut in standard feed for 2-6 days. Single point (90 min) intra
      peritoneal glucose tolerance tests were used to follow glucose tolerance up to 6
      months of age. Glucose intolerance was defined as over 3 SD above mean control
      values. Glucose intolerance was found in 3 of 51 male and 4 of 33 female adult
      mice which were fed the betel diet (p < 0.01). Studies on the progeny of these
      mice are presented separately for animals studied in Aberdeen (Group 1) and
      London (Group 2). In matings of Group 1 betel-fed parents glucose intolerance was
      found in 4 of 25 male and 1 of 22 female F1 offspring, with significant
      hyperglycaemia in F1 males born to hyperglycaemic but not to normoglycaemic
      mothers (p < 0.01). In the F2 generation 4 of 23 males and 1 of 16 females and in
      the F3 generation 1 of 16 males and 0 of 20 females were glucose intolerant. In
      the Group 2 studies where betel-fed parents were mated to normal controls glucose
      intolerance was found in 10 of 35 male and 10 of 33 female F1 progeny (p <
      0.005), and mean islet areas were increased in offspring of betel-fed parents (p
      < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150231
TI  - Insulin receptor dephosphorylation by phosphotyrosine phosphatases obtained from
      insulin-resistant obese mice.
AB  - To study the possible involvement of phosphotyrosine phosphatases in insulin
      resistance, the ability of cytosolic and membrane preparations to dephosphorylate
      insulin receptors was examined in lean and goldthioglucose-treated insulin
      resistant and obese mice. Preparations were obtained from liver, heart, diaphragm
      and hindleg muscle and their phosphotyrosine phosphatase activities were measured
      using an  immunoenzymatic assay with phosphorylated insulin receptors as
      substrate. Liver cytosolic and particulate phosphotyrosine phosphatases were more
      potent than preparations from other tissues and were able to almost completely
      dephosphorylate the insulin receptor in a dose- and time-dependent manner. No
      change was observed in cytosolic and membrane-associated phosphotyrosine
      phosphatases in liver, diaphragm, and heart of obese mice compared with lean
      mice. In contrast, cytosolic, but not membrane-associated, phosphotyrosine
      phosphatase activity was decreased in hindleg muscles of obese mice. These
      results suggest that the regulation of phosphotyrosine phosphatases is tissue
      specific. In addition, alterations in total phosphotyrosine phosphatase activity
      do not appear to play an important role in insulin resistance in all tissues of
      obese mice, although specific changes cannot be excluded.

PMID- 8150232
TI  - Autoantibodies against a novel 51 kDa islet antigen and glutamate decarboxylase
      isoforms in autoimmune polyendocrine syndrome type I.
AB  - Beta-cell function and islet cell antibodies were studied in six patients with
      autoimmune polyendocrine syndrome type I. All suffered from mucocutaneous
      candidiasis, five had adrenocortical insufficiency and three hypoparathyroidism.
      All sera contained high titres of antibodies staining islets of Langerhans.
      Reactivity against glutamate decarboxylase, predominantly the 65 kDa isoform, was
      detected by immunoprecipitations and Western blots in five of the six sera, and
      all six sera immunoprecipitated a 51 kDa antigen from [35S]-methionine labelled
      rat islet cell lysates. No reactivity against this latter antigen was found in
      sera of patients with Type 1 (insulin-dependent) diabetes mellitus (n = 9),
      Graves' disease (n = 5), autoimmune gastritis (n = 4), idiopathic Addison's
      disease (n = 7), or stiff-man syndrome (n = 2). The 51 kDa antigen was also
      detected by Western blots using homogenates of rat islets and autoimmune
      polyendocrine syndrome type I patient sera, whereas no such reactivity was found
      with homogenates of testes, adrenals, small intestine, spleen, exocrine pancreas
      or brain. Moreover, the 51 kDa antigen was present in the rat insulinoma cell
      line RINm 5F but not in the SV-40 transformed, monkey kidney cell line COS, when
      examined by immunoprecipitations of [35S]-methionine labelled cell lysates and by
      Western blots. None of the patients with autoimmune polyendocrine syndrome type I
      had symptoms of diabetes and their insulin responses to glucose challenge were
      normal. The data illustrate that patients with autoimmune polyendocrine syndrome
      type I present an autoimmune response against islets of Langerhans, which is
      apparently different from that associated with classic Type 1 diabetes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8150233
TI  - Presentation and progress of childhood diabetes mellitus: a prospective
      population-based study. The Bart's-Oxford Study Group.
AB  - We surveyed the clinical presentation, initial management and subsequent course
      of a prospectively registered, population-based cohort of 230 patients with Type
      1 (insulin-dependent) diabetes mellitus diagnosed before age 21 years in the
      Oxford Regional Health Authority area in 1985 and 1986. Clinical details from the
      time of diagnosis were available on 219 patients. Thirty-four (16%) were in
      severe ketoacidosis with pH less than 7.10 or plasma bicarbonate less than 10
      mmol/l, and 21 (10%) had mild to moderate ketoacidosis with pH 7.10-7.35 or
      plasma bicarbonate 10-21 mmol/l. One child died in ketoacidosis. Presentation in
      severe ketoacidosis was most common in children under age 5 years (p < 0.05), and
      ketoacidosis of any degree was less frequent in older children (0.05 < p < 0.01)
      and those with a parent or sibling with diabetes (p < 0.01). Within 4 years of
      diagnosis, 55 of 211 patients (26%) experienced severe hypoglycaemia, which in 31
      (15%) led to one or more admissions. Readmission for unstable glycaemic control
      excluding acute hypoglycaemia occurred at least once within 1 year of diagnosis
      in 13% and within 4 years in 28%, and was more common in girls, in children aged
      less than 10 years at diagnosis, and those with a history of severe
      hypoglycaemia. A second cohort of 97 similar patients was recruited in 1990. The
      rates of admission at diagnosis (79%), severe ketoacidosis (13%) and mild to
      moderate ketoacidosis (13%) did not differ from the 1985/1986 cohort.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8150235
TI  - A high weight gain early in life is associated with an increased risk of type 1
      (insulin-dependent) diabetes mellitus.
AB  - Growth during the first years of life in relation to type of feeding in infancy
      was retrospectively studied in an unselected population-based group of 297
      children who had been diagnosed with Type 1 (insulin-dependent) diabetes mellitus
      before the age of 15 years (probands) and 792 individually-matched referent
      subjects. Reliable data were collected from child welfare clinics. Probands
      weighed slightly less at birth but their weight gain at 6, 9, 18 and 30 months of
      age was significantly greater (p < 0.02) than that of referent children. The
      weight gain of children who had never been breast-fed was more marked than that
      of breast-fed children; this was found for both probands and referent children.
      But also among exclusively breast-fed children (> 2 months), probands gained
      significantly more in weight from birth up to 18 and 30 months of age than
      exclusively breast-fed referent children. Early weight gain appears to be a risk
      factor for development of Type 1 diabetes. The lower weight gain in breast-fed
      compared to non-breast-fed children may explain the protective effect of breast
      feeding against Type 1 diabetes observed in several studies.

PMID- 8150234
TI  - Effect of hyperglycaemia on gallbladder motility in type 1 (insulin-dependent)
      diabetes mellitus.
AB  - Patients with diabetes mellitus are at increased risk of developing gallstones.
      This has been attributed, among other factors, to alterations in gallbladder
      motility in the presence of autonomic neuropathy. Since high blood glucose
      concentrations impair gastric emptying in diabetic patients, we have investigated
      the effect of acute hyperglycaemia on gallbladder motility. Seven Type 1 (insulin
      dependent) diabetic patients were studied twice during euglycaemia (blood glucose
      5 mmol/l) and hyperglycaemia (blood glucose 15 mmol/l) using a clamp technique.
      In addition, seven healthy volunteers were studied during euglycaemia and
      hyperglycaemia. Gallbladder volumes, measured with ultrasonography, were studied
      before and during infusion of step-wise increasing doses of cholecystokinin-33,
      0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1, each dose for 30 min. Mean basal
      gallbladder volumes were not significantly different in the four experiments.
      Administration of cholecystokinin resulted in significant (p < 0.05) dose
      dependent reductions in gallbladder volume in all experiments. During euglycaemia
      the gallbladder contraction in diabetic patients was not significantly different
      from the control subjects. During hyperglycaemia the gallbladder contraction in
      the diabetic patients was significantly (p < 0.05) reduced compared to
      euglycaemia only during infusion of 0.25 Ivy Dog Unit.kg-1.h-1 of cholecystokinin
      (19 +/- 6% vs 33 +/- 6%). Compared to euglycaemia, during hyperglycaemia the
      gallbladder contraction in the control subjects was significantly (p < 0.05)
      reduced during infusion of 0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1 of
      cholecystokinin (14 +/- 4% vs 31 +/- 3%; 42 +/- 6% vs 65 +/- 5%; 74 +/- 4% vs 90
      +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150236
TI  - The natural history of pre-type 1 (insulin-dependent) diabetes mellitus in
      patients with autoimmune endocrine diseases.
AB  - An 11-year prospective study was carried out in 180 non-diabetic patients with
      organ-specific autoimmune diseases to evaluate islet cell antibodies in
      predicting Type 1 (insulin-dependent) diabetes mellitus. Islet cell antibodies
      were characterised according to titres, persistence, complement-fixing ability,
      and pattern. During follow-up, 14 of 46 patients with islet cell antibodies
      persistently greater than 5 Juvenile Diabetes Foundation Units (JDF-U) (30.4%),
      none of 23 with islet cell antibodies between 2.5 and 5 JDF-U or fluctuating, and
      3 of 109 without islet cell antibodies (2.7%), developed diabetes. The cumulative
      risk of developing diabetes was 70%, 0%, and 4%, respectively. All the patients
      who developed diabetes were females. Eight progressed to insulin-dependence
      acutely, four showed a transient period of non-insulin-dependence, while two were
      still insulin-free. No difference was found in titres of islet cell antibodies
      for the risk of diabetes. Complement-fixing islet cell antibodies enhanced the
      cumulative risk for the disease in patients with conventional islet cell
      antibodies at low-middle (> or = 2.5-40 JDF-U), but not at high (> or = 80 JDF-U)
      titres. Forty-two patients with islet cell antibodies were investigated for the
      whole or the selective pattern. In the presence of the whole pattern the
      cumulative risk for diabetes rose to 100%, while with the selective pattern it
      declined to 34%. The whole pattern was found in 83% of patients who developed
      Type 1 diabetes acutely. In patients with organ-specific autoimmune diseases, the
      whole islet cell antibody pattern greatly enhances the prediction for diabetes.

PMID- 8150237
TI  - Experimental Biology 94. Part I. Anaheim, California, April 24-28, 1994.
      Abstracts.

PMID- 8150238
TI  - American Society for Biochemistry and Molecular Biology, 85th Annual meeting.
      Washington, D.C., May 21-25, 1994. Abstracts.

PMID- 8150239
TI  - Digestive Disease Week and the 95th Annual Meeting of the American
      Gastroenterological Association. New Orleans, Louisiana, May 15-18, 1994.
      Abstracts.

PMID- 8150240
TI  - [Climacteric--from the viewpoint of the established gynecologist. Interview by
      Jeanette Gerhardt].

PMID- 8150241
TI  - [How intestinal diseases, nutrition, smoking and alcohol modify the action of
      oral contraceptives].

PMID- 8150242
TI  - [The forgotten pioneers of the negative feedback of estrogens].

PMID- 8150243
TI  - [Error in patient education before delivery--the newest decision of the BGH].

PMID- 8150244
TI  - [Controversial attitude to mammography screening in asymptomatic women between 40
      and 50 years of age].
AB  - The results of screening studies conducted in the United States and in Europe in
      females between the ages of 40 and 50 are analysed. It is shown, that the results
      of this study on mortality reduction are less favourable, the poorer the
      technique of mammography (foregoing of general two-view mammography) and the
      longer the time interval between two mammography screenings. Arguments are
      presented, that are brought forward when declining to perform general mammography
      screening in this age group. The author's own results, obtained in the Hamburg
      mammography screening study, which included from 1971 to 1986 also premenopausal
      women, show, that the survival rates of patients below 50 years of age with
      mammographically detected carcinomas of the breast do not differ from those in
      patients older than 50 years, according to a relevant age group classification.
      The advances in the technique of mammography in recent years are analysed on the
      basis of the author's own patient material. It is evident, that the positive
      predictive value has been doubled, especially in the age group between 40 and 50.
      An analysis of the distribution of diagnosed noninvasive carcinomas compared with
      the invasive carcinomas reveals, that particularly this age group has the highest
      percentage of identification of prognostically favourable carcinoma stages.
      Further analyses show, why the randomised European mammography studies could not
      yield a significant mortality rate improvement. A prerequisite for the inclusion
      of mammography screening in the legally prescribed early detection of carcinoma
      examinations, however, are the quality controls, whose realisation, in our health
      system, will have to be confirmed by the German mammography study.

PMID- 8150245
TI  - [Etiologic classification of premature labor and its importance for prevention].
AB  - A retrospective analysis of 202 premature deliveries before 37 weeks was
      performed to identify major pathologies related to preterm delivery. The most
      frequent pathologies were premature rupture of membranes (32.4%), premature
      labour without recognisable aetiology (19.1%), hypertensive diseases in pregnancy
      (15.6%), multiple pregnancies (14.4%), malformations (9.8%) and bleeding in the
      3rd trimester (6.4%). The majority of premature deliveries are related to 4 major
      pathogenetic disturbances: infection, problems of placentation, pathology of the
      foetus, pathology of the uterus. Each of these pathologies can lead to premature
      delivery via premature labour, premature rupture of membranes or termination of
      pregnancy for foetal or maternal pathology. In one third of premature labour, in
      another preterm premature rupture of membranes with labour after a variable
      latent period led to delivery, and in the remaining third, delivery was performed
      by a primary caesarean section or induction of labour for foetal or maternal
      pathology. Less than 25% cases were considered as failures of tocolytic
      treatment. Tocolytics, steroids or antibiotics, may help to improve the survival
      rate in particular with very low birth-weight infants at less than 30 weeks
      gestation. A decrease in the overall rate of prematurity can be achieved only by
      a general improvement of the socio-economic working and living conditions of the
      female population, in particular of pregnant women.

PMID- 8150246
TI  - [Vaginal sonography of the cervix in twin pregnancies].
AB  - In a prospective study of 97 uncomplicated twin pregnancies, vaginosonographic
      cervix measurements of length, thickness and width of the internal os were
      performed. Furthermore, a group of 113 uncomplicated primipara was measured by
      vaginosonography. The twin pregnancies were examined sonographically at 4-5 week
      intervals between the 14th and 34th week of gestation. The results of the
      measurements were correlated between these two groups in accordance with duration
      of pregnancy and the number of deliveries. The results showed in general, that
      the cervical length of multipara-multiple pregnancy is longer than in the
      primipara-multiple pregnancy. Between the 13th and 17th week of gestation the
      cervix of primipara showed a length of 48.1 +/- 2.1 mm, the multipara twins
      showed a length of 52.3 +/- 3.4 mm. Between the 18th and 22nd gestational week,
      the primipara showed a cervical length of 49.4 +/- 3.6 mm and the multipara a
      length of 49.6 +/- 2.6 mm. In the 23rd to 27th week, the primipara had a cervical
      length of 39.4 +/- 2.4 mm, the multipara of 49.3 +/- 3.7 mm. From the 28th to
      33rd week, cervical length was reduced in primipara to 31.2 +/- 2.9 mm, and in
      multipara to 42.7 +/- 5.1 mm. In the normal group of multipara, the cervical
      length was slightly longer. The assessment of cervical thickness showed the
      widest cervices in multipara gemini followed by the primipara gemini, the
      smallest cervices were found in primipara-single pregnancies.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8150247
TI  - [Premature separation of the placenta--clinical findings and fetal monitoring].
AB  - In a study group of 41 pregnant women of postpartally confirmed placental
      abruption, the prognostic value of clinical and diagnostic findings was
      investigated. The incidence of placental abruption was 1.4% of all deliveries
      within a three-year interval. 51% of patients showed vaginal bleeding before
      delivery. Retroplacental haematoma was found in 49% of cases
      ultrasonographically. A total of 75% had a pathological CTG test. More than 95%
      of these findings occurred within 3 days before delivery. Abnormal Doppler flow
      findings in foetal vessels more than 3 days before delivery were seen in 62% of
      cases. In the last three days before delivery, 86% were abnormal. Preterm
      delivery before 37 weeks of gestation was registered in 82% of patients.
      Perinatal mortality amounted to 12%. The rate of severely dystrophic newborn was
      30%. Even in cases with lack of the clinical and/or sonographical findings, the
      possibility of placental abruption should be considered, if an acute
      deterioration of cardiotocographic or Doppler-sonographic findings.

PMID- 8150248
TI  - [Drug information in hormone substitution drugs].
AB  - The package leaflets of hormone preparations used for Hormone Replacement Therapy
      (HRT) in hypoestrogenaemic women contain contraindications, which are taken from
      the package insert of oral contraceptives: Clots in the blood vessels (thrombotic
      disorders), high blood fats, severe diabetes, abnormal red blood cells,
      deterioration of inherited deafness and jaundice not explained by infections,
      disturbances of the liver function and of existing or treated hormone-dependent
      tumours of the breast or of the lining of the womb. Numerous epidemiologic,
      animal-experimental and also clinical studies proved that the cardiovascular
      risk, hepatic discomfort and the influence on the blood system of oestradiol 17
      beta have to be evaluated completely differently compared to the
      ethinyloestradiol used in oral contraceptives; therefore, many of the listed
      contraindications must be reconsidered. In our review we try to emphasise this
      postulation by scrutinizing recent publications.

PMID- 8150249
TI  - [Trans-uterine fallopian tube catheterization--a noninvasive, ambulatory
      evaluation of fallopian tube patency].
AB  - In a prospective clinical study (March 89-June 91), we examined 114 infertile
      women to evaluate the diagnostic value of trans-uterine tubal cannulation with
      the injection of sterile fluid and consecutive sonographical control in the
      assessment of tubal patency. The results of this technique were compared with the
      findings of laparoscopy and/or hysterosalpingography. With the Jansen-Anderson
      Catheter (J-A-C) it was possible to reach the isthmic part of the tube without
      any analgesia or anaesthesia. 10 to 15 ml of sterile culture medium were
      injected. In case of tubal patency the fluid was detectable in the pouch of
      Douglas by transvaginal ultrasound. In 108 out of 114 women (94.7%), the
      cannulation of at least one tube was possible. All 97 patients with patent tubes
      (laparoscopy) were diagnosed correctly via the J-A-C. The three cases of proximal
      tubal occlusion were also diagnosed correctly, 8 patients with one or two-sided
      hydrosalpinx were also recognized. All five patients with bilateral hydrosalpinx
      were detected. Three women showed a unilateral hydrosalpinx in the laparoscopy.
      In these cases the diagnosis obtained by the J-A-C was once bilaterally patent
      and twice bilaterally distally occluded. Trans-uterine cannulation of the tubes
      with injection of sterile fluid and consecutive transvaginal sonography is an
      easy and safe method to evaluate the tubal status. It becomes possible thereby to
      prove tubal patency in a very early stage of diagnostics. Loss of time and futile
      treatment cycles (stimulations or inseminations in cases of tubal occlusion) can
      thus be avoided.

PMID- 8150250
TI  - [Tuboscopy--new developments for accurate tubal diagnosis].
AB  - A specially developed linear everting catheter (LEC) in combination with a
      microendoscope, enables for the first time the visualisation of the complete
      tubal mucosa from a vaginal approach. Preliminary results in using this technique
      are described. Physiological and pathological results of tubal mucosa can be
      presented, which will influence the diagnostic and therapeutic part of subsequent
      sterility treatment.

PMID- 8150251
TI  - [Granisetron, a new and potent antiemetic for treatment of cytostatic drug
      induced vomiting in gynecological malignancies].
AB  - The efficacy of Granisetron, a new and selective 5HT3-receptor-antagonist in the
      treatment of cytostatic induced emesis, was tested in the department of
      gynaecology and obstetrics of the University of Essen on 77 patients. The
      patients received cytostatic drugs with a high emetogenic potency (for example
      cisplatin) or with a moderately high emetogenic potency (for example
      cyclophosphamide). We were able to demonstrate the high antiemetic efficacy of
      Granisetron. We had in 63% of the cases a "complete response" during the first 24
      h after the chemotherapy and a "complete response" of 60% for the "delayed
      emesis". The observed adverse reactions such as constipation and headache were
      easily solved with standard laxatives or standard analgesics. Because of the high
      efficacy of Granisetron, which was combined with a low rate of side effects, it
      was possible to give to all the 77 patients the complete and necessary
      chemotherapy, so that no patient refused to receive the chemotherapy just because
      of nausea or emesis. The use of Granisetron is therefore a major step forward in
      the care of patients receiving chemotherapy because nausea and emesis can be
      treated effectively.

PMID- 8150252
TI  - [Infected ovarian vein thrombosis in infection with Ureaplasma urealyticum and
      Mycoplasma hominis after cesarean section].
AB  - Puerperal ovarian vein thrombophlebitis (POVT) is a rare but severe complication
      of the post partum period. We report on a patient, who developed a POVT based on
      an infection with Ureaplasma urealyticum and Mycoplasma hominis. Problems of
      diagnostic procedures in cases of POVT and the role of ureaplasma and mycoplasma
      in infectious obstetric complications are discussed.

PMID- 8150253
TI  - [Hyperreactio luteinalis in pregnancy].
AB  - We report on the extremely rare case of ovarian overstimulation in a single
      pregnancy without prior hormonal stimulation therapy. During the 26th week of
      gestation ultrasound examination showed a 103 x 57 x 78 mm polycystic tumour with
      echogenic structures inside the cysts, located behind the uterus. Further
      management consisted of laparotomy with partial resection of a cystic part of the
      left ovary. Frozen section examination confirmed the diagnosis of hyperreactio
      luteinalis and excluded malignancy. To avoid torsion of the ovaries, cysts from
      both sides were aspirated. On day 8 and 18 after surgery, sonography revealed no
      pathological finding. In the 40th week of gestation, a healthy baby was
      delivered. The possibility of a hyperreactio luteinalis has to be kept in mind,
      when cystic solid tumours of the ovaries are diagnosed during pregnancy. A
      conservative management is appropriate, because a normal spontaneous remission
      occurs after delivery.

PMID- 8150254
TI  - [Cavernous hemangioma of the uterine cervix in pregnancy].
AB  - Cavernous haemangiomas of the uterine cervix are very rare and usually harmless.
      Nevertheless, the case reported of a 31-year old multiparous woman in the 34+1
      gestational week, who presented herself with a fast growing cervical haemangioma,
      indicates, that this benign tumour may cause obstetrical complications.

PMID- 8150255
TI  - [Is moderate labor stress for newborn infants an advantage? Pilot study of
      postpartum weight gain of 791 newborn infants].
AB  - Neonatal weight development in the first 5 postpartal days is favourably affected
      by intrapartal stress factors. 1. Pathological CTS during delivery were
      registered for every 8th infant. Slight postpartal weight loss occurred twice as
      often in this group, compared with the other newborns. The incidence of distinct
      weight decrease was the same in both groups. On the 5th postpartal day, almost
      double the number of infants with pathological CTG had either reached or exceeded
      their birth weight, compared to the normal CTG group. 2. Green amniotic fluid
      coincided with slight weight loss in double the number of affected children,
      compared to the rest of the study group. 3. Slight postpartal weight loss was
      seen more often in neonates with umbilical cord-pH values of up to 7.20 than in
      infants with pH values exceeding 7.20. Distinct postpartal weight loss was,
      however, not more frequent in the former group. 4. The birth mode of the 791
      newborn was as follows: 16% Caesarean section, 7% vaginal forceps delivery, and
      77% spontaneous birth. On the 5th postpartal day 11% of the forceps-delivery
      infants, 17% of the spontaneous births and 30% of the neonates delivered by
      Caesarean section had not regained their birth weight. 5. PDA on vaginal delivery
      was applied to one-third of the women. Slight postpartal weight loss was seen
      twice as often in these infants, compared to the others. In conclusion, the study
      reflected, that intrapartal stress aids transition to extrauterine life via
      "catecholamine peaks". Our current birth monitoring methods may therefore require
      revalidation with regard to set pathologic limits, using the adaptation parameter
      of neonatal weight development.

PMID- 8150256
TI  - Genetic diversity of the iron-binding protein (Fbp) gene of the pathogenic and
      commensal Neisseria.
AB  - The pathogenic Neisseria and most commensal Neisseria species produce an iron
      binding protein (Fbp) when grown under iron-limited conditions. In the current
      study, we confirmed the presence of Fbp, as well as DNA sequences homologous to
      the gonococcal fbp, in strains of N. gonorrhoeae, N. meningitidis, N. cinerea, N.
      lactamica, N. subflava, N. kochii and N. polysaccharea. The fbp genes from these
      strains were amplified by the polymerase chain reaction, digested with StuI or
      RsaI, and the restriction patterns examined. The patterns for the gonococcal and
      meningococcal fbp were virtually identical; however, variations were observed in
      the fbp sequences of the commensal Neisseria species. N. flavescens, N. mucosa,
      N. sicca, N. ovis and Branhamella catarrhalis, did not produce Fbp as detected by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and reactivity with an
      Fbp specific monoclonal antibody, nor did they hybridize to an fbp-specific DNA
      probe.

PMID- 8150257
TI  - Induction of resistance to novobiocin in the novobiocin-producing organism
      Streptomyces niveus.
AB  - During growth of Streptomyces niveus wild-type in the novobiocin production
      medium CDM the resistance of mycelia to novobiocin rises from about 25
      micrograms/ml to over 200 micrograms/ml. (S. lividans, a novobiocin-sensitive
      strain, is resistant to approx. 10 micrograms/ml novobiocin.) The initial period
      of low level resistance extends from the time of inoculation of the culture until
      approx. 70 h when the culture is still in the growth phase. High level resistance
      is initiated before the start of novobiocin production and rises rapidly to a
      maximum level beyond the end of the growth phase. The rise in pH of the
      unbuffered CDM medium which occurs during S. niveus fermentation was shown not to
      be the cause of the change in novobiocin resistance. However, mycelia-free CDM
      from S. niveus cultures expressing high level novobiocin resistance was shown to
      contain a factor which induced high level novobiocin resistance in germinating S.
      niveus spores. Kinetic studies revealed that the inducer first appears in the
      culture medium before the switch to high level resistance begins and reaches its
      highest concentration before resistance reaches its maximum level.

PMID- 8150258
TI  - Cell-cycle mutations among the collection of Saccharomyces cerevisiae dna
      mutants.
AB  - The temperature-sensitive dna mutants of the budding yeast Saccharomyces
      cerevisiae (Dumas et al. (1982) Mol. Gen. Genet. 187, 42-46) are more inhibited
      in DNA synthesis than in protein synthesis. These properties are also
      characteristic of many yeast mutations that inhibit progress through the cell
      cycle. Therefore we surveyed the collection of dna mutants for cell-cycle
      mutations. By genetic complementation we found that dna1 = cdc22, dna6 = cdc34,
      dna19 = cdc36, and dna39 = dbf3. Furthermore, by direct gene cloning we found
      that the dna26 mutation is allelic to prt1 mutations, which are known to exert
      primary inhibition on protein synthesis. This protein-synthesis mutation exerts a
      dna phenotype due to cell-cycle inhibition: prt1 mutations can block the
      regulatory step of the cell cycle while allowing significant amounts of protein
      synthesis to continue. Our non-exhaustive screening suggests that the dna mutants
      may house other mutations that affect the yeast cell cycle.

PMID- 8150259
TI  - Extracellular protease and phospholipase C are controlled by the global
      regulatory gene gacA in the biocontrol strain Pseudomonas fluorescens CHA0.
AB  - Pseudomonas fluorescens strain CHA0 protects plants from various root diseases.
      Antibiotic metabolites synthesized by this strain play an important role in
      disease suppression; their production is mediated by the global activator gene
      gacA. Here we show by complementation that the gacA gene is also essential for
      the expression of two extracellular enzymes in P. fluorescens CHA0: phospholipase
      C and a 47-kDa metalloprotease. In contrast, the production of another exoenzyme,
      lipase, is not regulated by the gacA gene. Protease, phospholipase and
      antibiotics of P. fluorescens are all known to be optimally produced at the end
      of exponential growth; thus, the gacA gene appears to be a general stationary
      phase regulator.

PMID- 8150260
TI  - Purification and characterization of Bordetella calmodulin-like protein.
AB  - Bordetella calmodulin-like protein was purified from culture supernatant fluid of
      B. pertussis, B. parapertussis and B. bronchiseptica by successive chromatography
      on hydroxyapatite, Toyopearl HW-50F and QAE-Toyopearl 550C columns. The purified
      calmodulin-like protein appeared to be homogeneous by SDS-polyacrylamide gel
      electrophoresis. The apparent molecular mass of calmodulin-like protein on SDS
      polyacrylamide gel electrophoresis was 10 kDa, which was smaller than bovine
      brain calmodulin (17 kDa). The purified calmodulin-like protein activated both
      Bordetella adenylate cyclase and mammalian phosphodiesterase in a Ca(2+)
      dependent manner. This activation was inhibited by calmodulin antagonists. The
      calmodulin-like protein, like calmodulin, was retained by a hydrophobic resin in
      the presence of Ca2+ and eluted by the addition of EDTA. These results indicated
      that the Bordetella calmodulin-like protein is closely related to calmodulin. As
      a putative calmodulin the extracellular calmodulin may be involved in Bordetella
      pathogenesis.

PMID- 8150261
TI  - The Caulobacter crescentus holdfast: identification of holdfast attachment
      complex genes.
AB  - Caulobacters are biofilm bacteria that attach to surfaces via a holdfast, an
      adhesive expressed at discrete cell surface sites. We have described a cluster of
      at least three genes involved in the adhesive attachment of the holdfast of
      Caulobacter crescentus CB2A to the cell, analyzing the sequence of two genes,
      hfaAB. Here we report hfaC and a fourth open reading frame, hfaD. hfaC predicts a
      protein of 41 kDa homologous to ATP-binding transport-related proteins, with ChvD
      of Agrobacterium tumefaciens as best match. HfaD is predicted to be 28 kDa with
      three membrane spanning regions. hfaA, hfaC, and hfaD were expressed in
      Escherichia coli; Western analysis with antisera against a holdfast-enriched
      preparation indicated HfaA was likely holdfast-associated. Cumulative findings
      predict HfaA and HfaB are developmentally regulated and one or both enhance hfaC
      transcription, HfaA is a mediator of adhesion, possibly between holdfast and a
      membrane-bound HfaD, and HfaC mediates export of an unidentified component
      required for holdfast attachment.

PMID- 8150262
TI  - The binding of hepatitis A virus to cell surfaces shows evidence of positive co
      operativity.
AB  - Radio-iodinated hepatitis A virus binds to cultured mammalian cells in a
      saturable manner, with about 1.4 x 10(3) sites/cell and a S0.5 of about 1.4 x 10(
      11) M for FRhK-4 cells. This binding to FRhK-4 cells shows evidence of positive
      co-operativity, with a Hill coefficient of 2.1 (+/- 0.1). This implies that the
      cellular receptor for the virus may have multiple binding sites and that the
      affinity of HAV for its receptor is increased if one of the binding sites is
      occupied by virus. Binding is completely blocked by two neutralising monoclonal
      antibodies, which also inhibit viral haemagglutination. A non-neutralising
      monoclonal antibody partially inhibits binding to FRhK-4 cells, but has no effect
      on haemagglutination.

PMID- 8150263
TI  - Microorganisms surviving for 5300 years.
AB  - Recently, the well-preserved corpse of a prehistoric man with an age of
      approximately 5300 years bp was discovered in the Central European Alps. Analysis
      of materials associated with the individual has revealed the presence of
      microorganisms which are believed to have survived since the time of death. So
      far, two fungi have been isolated and identified as species of the genera
      Chaetomium and Absidia, respectively. In addition, we have obtained one bacterial
      isolate which we have identified as a Streptomyces species. Our findings
      demonstrate that microorganisms can remain viable under appropriate circumstances
      for thousands of years. The isolates may enable us to study evolutionary trends
      within microorganisms.

PMID- 8150264
TI  - Haemolytic activity associated with parasporal inclusion proteins of mosquito
      specific Bacillus thuringiensis soil isolates: a comparative neutralization
      study.
AB  - Solubilized parasporal inclusions of the three mosquito-specific Bacillus
      thuringiensis isolates belonging to three different H serovars, co-isolated from
      a single soil microhabitat, showed haemolytic activity towards mammalian
      erythrocytes. Neutralization tests with antibodies against whole inclusion
      proteins resulted in crossed neutralization of haemolytic activity among the
      isolates and the type strain of B. thuringiensis serovar kyushuensis, indicating
      that the three soil isolates produce toxins related to the CytB toxin. No cross
      neutralization occurred between the type strain of B. thuringiensis serovar
      israelensis and the three soil isolates.

PMID- 8150265
TI  - Role of the phosphotransferase system in Escherichia coli strains deficient in
      hexose phosphate transport.
AB  - In Escherichia coli, glucose 6-phosphate is transported via the Uhp system which
      is inducible by glucose 6-phosphate. We showed that, in a uhp-deficient strain,
      glucose 6-phosphate was dephosphorylated in the periplasm and that the resulting
      glucose was subsequently transported into the cells via the phosphotransferase
      system. The uptake of glucose generated from glucose 6-phosphate allowed the
      bacteria to produce an increased level of cAMP compared to cells grown on non
      limiting concentrations of glucose.

PMID- 8150266
TI  - Mineralization of monofluorobenzoate by a diculture under sulfate-reducing
      conditions.
AB  - A mesophilic, dehalogenating, sulfate-reducing diculture was isolated from an
      anaerobic lake sediment. One strain of the diculture is proposed to be an
      endospore-forming Desulfotomaculum species, the second strain was a vibrioid,
      motile and non-sporeforming species which is tentatively assigned to the genus
      Desulfovibrio. The diculture was able to mineralize 4- and 2-fluorobenzoate both
      isomers being incompletely oxidized with the release of acetate, which was
      subsequently used by both sulfate-reducing strains. Other electron donors used
      for growth included benzoate, 3- and 4-hydroxybenzoate, protocatechuate,
      catechol, phenol, 2,5-dimethoxyphenol, fatty acids up to C8, malate and pyruvate.
      The culture obtained from a freshwater habitat grew optimally at NaCl
      concentrations of 0.3-0.5 g l-1, 33-37 degrees C, and pH 7.4. Our experiments
      showed that certain fluorinated aromatic hydrocarbons could serve as sole sources
      of carbon and energy for sulfate-reducing bacteria.

PMID- 8150267
TI  - Azide-resistant mutants in Acinetobacter calcoaceticus A2 are defective in
      protein secretion.
AB  - Azide, an inhibitor of ATPase, and a specific inhibitor of protein export was
      used in order to select for protein secretion mutants in Acinetobacter
      calcoaceticus A2. Two such mutants were isolated that were azide-resistant and
      defective in the general protein transport system. The mutation also conferred
      additional phenotypic changes, including an inability to grow on minimal media or
      at 40 degrees C. The existence of protein secretion mutants with a selectable
      phenotype may be useful for the genetic study of protein export.

PMID- 8150268
TI  - Preparation of recombinant glycoprotease of Pasteurella haemolytica A1 utilizing
      the Escherichia coli alpha-hemolysin secretion system.
AB  - Three murine monoclonal antibodies were prepared against the recombinant
      glycoprotease of Pasteurella haemolytica A1 expressed in Escherichia coli. These
      monoclonal antibodies were able to recognize the authentic glycoprotease from P.
      haemolytica A1 culture supernatant. A recombinant plasmid which contained most of
      the glycoprotease gene of P. haemolytica A1 fused with the secretion signal
      sequence from hlyA of the E. coli alpha-hemolysin determinant was constructed.
      This recombinant plasmid expressed a fusion protein (Gcp-F) which was secreted
      into the culture supernatant by E. coli cells when the alpha-hemolysin secretion
      functions HlyB and HlyD are supplied in trans. Gcp-F could be readily recovered
      from the supernatant free from other cellular materials and is suitable for use
      in vaccine trials and challenge experiments in animals.

PMID- 8150269
TI  - Isolation and characterization of the dsRNA virus from the yeast Endomyces
      magnusii.
AB  - Virus-like particles (VLPs) have been isolated from the yeast Endomyces magnusii.
      The VLPs measure 43 nm in diameter and contain six species of dsRNA (0.78, 0.83,
      1.77, 1.84, 2.64, 4.30 kb respectively). E. magnusii produces a 'toxic' protein,
      which reduces the growth, and changes the colony morphology, of sensitive strains
      of Hansenula sp. growing on solid media. All strains of E. magnusii tested
      produced the 'toxin' and contained the VLPs. Current procedures of curing failed
      to destroy the ability to produce the 'toxin'.

PMID- 8150270
TI  - Children's home environments, health, behavior, and intervention efforts: a
      review using the HOME inventory as a marker measure.
AB  - The HOME inventories have been widely used in studies of children's health and
      development. This measure of the quality of stimulation and support available to
      a child in the home environment reflects the family's social status as well as
      other family ecological factors, but there is marked variability of scores within
      social classes. Information derived from HOME also reflect parental
      characteristics such as marital status, mental health status, and substance
      abuse. Subscales from the inventories show theoretically meaningful links to
      children's health, growth, language, intelligence, social competence, and
      temperament. Although the scales have been used in many different countries, it
      is unclear whether they precisely capture differences in environmental quality in
      all cultures. HOME does, however, seem to be sensitive to genetic variations in
      children and to environmental manipulations such as parent education programs and
      early intervention programs.

PMID- 8150271
TI  - There is more to emotion than goal attainment.
AB  - The current conflict theory of emotion states that emotions arise at junctures of
      plans in which circumstances show the likely attainment or nonattainment of a
      goal and in which those circumstances include other plans and other goals. But
      emotions often arise from side goals rather than from the goal being aimed at.
      This article raises the question of what a goal is and suggests that any goal
      statement should include goals about a person's identity, self-definition, and
      cognitive development. This approach questions the sharp distinction usually
      drawn between goal and cognitive structure and puts forward a broader view of
      emotion as the awareness of important cognitive change that results from the
      validation or invalidation of one's cognitive system or a part of it. This view
      emphasizes the role of having a model of the self and shows how emotions can be
      defined as beliefs about changes in belief. This approach suggests that, just as
      pain monitors changes in physical states, so emotions monitor changes in mental
      states, providing high-level information for the management of cognitions.
      Another function of emotion is to identify the type and magnitude of
      inconsistencies between two mental states in a timely manner; such identification
      avoids the need for logical proof or numerical calculation.

PMID- 8150272
TI  - The role of negative affect and positive affect in stress, depression, self
      esteem, assertiveness, Type A behaviors, psychological health, and physical
      health.
AB  - Dua (1989) constructed the Thoughts and Real-Life Experiences Scale (THARL) to
      assess the degree of positive and negative affect experienced by people as a
      result of their thoughts and day-to-day experiences. This monograph reports on a
      number of studies designed to investigate the relationship between negative and
      positive affect caused by thoughts and day-to-day experiences and psychological
      health, psychological problems, and physical health. Results showed that a
      preponderance of self-reported negative affect was related to higher levels of
      stress, depression, poor psychological well-being, poor psychological health,
      lower self-esteem and poor self-reported retrospective physical health. A
      preponderance of negative affect was associated with only one of the two measures
      of prospective physical health, namely, the number of visits to doctors for
      medical problems over a period of 4 weeks. Positive affect was not associated
      with either self-esteem or physical health. Assertiveness and Type A/B behaviors
      were not associated with either negative or positive affect. Also, of the two
      measures of negative affect, that caused by thoughts seemed to be a better
      predictor of health, well-being, and psychological problems than that caused by
      day-to-day experiences.

PMID- 8150273
TI  - The transformation of genetics by DNA: an anniversary celebration of Avery,
      MacLeod and McCarty (1944).

PMID- 8150274
TI  - Genetic properties of temperature-sensitive folding mutants of the coat protein
      of phage P22.
AB  - Temperature-sensitive mutations fall into two general classes: those generating
      thermolabile proteins; and those generating defects in protein synthesis, folding
      or assembly. Temperature-sensitive mutations at 17 sites in the gene for the coat
      protein of Phage P22 are of the latter class, preventing the productive folding
      of the polypeptide chain at restrictive temperature. We show here that, though
      the coat subunits interact intimately to form the viral shell, these temperature
      sensitive folding (TSF) mutations were all recessive to wild type. The mutant
      polypeptide chains were not rescued by the presence of wild-type polypeptide
      chains. Missense substitutions in multimeric proteins frequently exhibit
      intragenic complementation; however, all pairs of coat protein TSF mutants tested
      failed to complement. The recessive phenotypes, absence of rescue and absence of
      intragenic complementation are all accounted for by the TSF defect, in which
      destabilization of a folding intermediate at restrictive temperature prevents the
      mutant chain from reaching the conformation required for subunit/subunit
      recognition. We suggest that absence of intragenic complementation should be a
      general property of TSF mutations in genes encoding multimeric proteins. The
      spectra of new loci identified by isolating second-site suppressors and synthetic
      lethals of temperature sensitive mutants will also differ depending on the nature
      of the defect. In the case of TSF mutations, where folding intermediates are
      defective rather than the native molecule, the spectra of other genes identified
      should shift from those whose products interact with the native molecule to those
      whose products influence the folding process.

PMID- 8150275
TI  - Insertional mutations in the yeast HOP1 gene: evidence for multimeric assembly in
      meiosis.
AB  - The HOP1 gene of Saccharomyces cerevisiae has been shown to play an important
      role in meiotic synapsis. In this study we analyzed the mechanism of this
      function by phenotypic characterization of novel in-frame linker-insertion
      mutations located at various sites throughout the HOP1 coding sequence. Among 12
      mutations found to cause defects in meiotic recombination and spore viability,
      three were temperature-sensitive for the spore viability defect. Although
      substantial meiotic recombination was found for these conditional alleles at the
      restrictive temperature, the level of exchange measured in spo13 meiosis was
      reduced in some of the monitored intervals, indicating that nondisjunction
      resulting from a deficit in crossing over could account for SPO13 spore
      inviability. Intragenic complementation between linker-insertion alleles was
      assessed by testing the viability of spores generated from heteroallelic diploids
      after SPO13 meiosis. Complex patterns of complementation and enhancement of the
      spore-inviability phenotype indicate that HOP1 functions in a multimeric complex.
      In addition, the ability of alleles which map near the carboxyl terminus to
      complement several other alleles provides evidence for a functional domain in
      this region of the protein. Two previously identified multicopy suppressors of
      the conditional hop1-628ts allele were tested for their effects in cells bearing
      the linker-insertion hop1 alleles. Overexpression of REC104 from a 2 mu plasmid
      was shown to enhance the spore viability of every allele tested, including a hop1
      disruption allele. On the other hand, suppression by overexpression of RED1 from
      a 2 mu plasmid was found only for allele hop1-628ts. Surprisingly, similar
      overexpression of RED1 in strains bearing several other conditional hop1 linker
      insertion alleles caused enhanced spore lethality. This finding, in conjunction
      with the evidence for a carboxy-terminal domain, provides new insight into the
      nature of interactions between the HOP1 and RED1 products in meiosis.

PMID- 8150276
TI  - The Yak1 protein kinase of Saccharomyces cerevisiae moderates thermotolerance and
      inhibits growth by an Sch9 protein kinase-independent mechanism.
AB  - The growth defect associated with the loss of yeast A kinase activity can be
      alleviated by the overexpression or deletion of two other kinases, Sch9 and Yak1,
      respectively. Using tests of epistasis, we have shown that Sch9 and Yak1 define
      separate signaling pathways and must, therefore, suppress the A kinase defect by
      different mechanisms. Nevertheless, the Yak1 kinase appears to regulate cellular
      processes that are under A kinase control. For example, acquisition of heat
      resistance is correlated with Yak1 kinase activity, such that YAK1-overexpressing
      cells are over 200-fold more resistant than isogenic yak1 strains. These results,
      for the first time, associate a phenotype, other than suppression of the A kinase
      growth defect, with the loss of Yak1 activity and argue a broader role for the
      Yak1 kinase in cell growth.

PMID- 8150277
TI  - A pleiotropic phospholipid biosynthetic regulatory mutation in Saccharomyces
      cerevisiae is allelic to sin3 (sdi1, ume4, rpd1).
AB  - Three mutants were identified in a genetic screen using an INO1-lacZ fusion to
      detect altered INO1 regulation in Saccharomyces cerevisiae. These strains harbor
      mutations that render the cell unable to fully repress expression of INO1, the
      structural gene for inositol-1-phosphate synthase. The Cpe-(constitutive
      phospholipid gene expression) phenotype associated with these mutations
      segregated 2:2, indicating that it was the result of a single gene mutation. The
      mutations were shown to be recessive and allelic. A strain carrying the tightest
      of the three alleles was examined in detail and was found to express the set of
      co-regulated phospholipid structural genes (INO1, CHO1, CHO2 and OP13)
      constitutively. The Cpe- mutants also exhibited a pleiotropic defect in
      sporulation. The mutations were mapped to the right arm of chromosome XV, close
      to the centromere, where it was discovered that they were allelic to the
      previously identified regulatory mutation sin3 (sdi1, ume4, rpd1, gam2). A sin3
      null mutation failed to complement the mutation conferring the Cpe- phenotype. A
      mutant harboring a sin3 null allele exhibited the same altered INO1 expression
      pattern observed in strains carrying the Cpe- mutations isolated in this study.

PMID- 8150279
TI  - Mutations in the yeast PDR3, PDR4, PDR7 and PDR9 pleiotropic (multiple) drug
      resistance loci affect the transcript level of an ATP binding cassette
      transporter encoding gene, PDR5.
AB  - The yeast pleiotropic (multiple drug) resistance gene PDR5 encodes a product with
      homology to a large number of membrane transport proteins including the mammalian
      multiple drug resistance family. In this study, we identified four genes on
      chromosome II that affect the steady-state level of PDR5 transcript in addition
      to a previously identified positive regulator, PDR1. The genes in question are
      PDR3, PDR4, PDR7 and PDR9. We also analyzed the interaction between PDR5 and
      YAP1. YAP1 encodes a positive regulator with a leucine zipper motif that causes
      pleiotropic drug resistance when overproduced. YAP1-mediated pleiotropic drug
      resistance is not dependent on the presence of PDR5 and must act through other
      genes.

PMID- 8150278
TI  - Characterization of glycogen-deficient glc mutants of Saccharomyces cerevisiae.
AB  - Forty-eight mutants of Saccharomyces cerevisiae with defects in glycogen
      metabolism were isolated. The mutations defined eight GLC genes, the function of
      which were determined. Mutations in three of these genes activate the RAS/cAMP
      pathway either by impairment of a RAS GTPase-activating protein (GLC1/IRA1 and
      GLC4/IRA2) or by activating Ras2p (GLC5/RAS2). SNF1 protein kinase (GLC2) was
      found to be required for normal glycogen levels. Glycogen branching enzyme (GLC3)
      was found to be required for significant glycogen synthesis. GLC6 was shown to be
      allelic to CIF1 (and probably FDP1, BYP1 and GGS1), mutations in which were
      previously found to prevent growth on glucose; this gene is also the same as
      TPS1, which encodes a subunit of the trehalose-phosphate synthase. Mutations in
      GLC6 were capable of increasing or decreasing glycogen levels, at least in part
      via effects on the regulation of glycogen synthase. GLC7 encodes a type 1 protein
      phosphatase that contributes to the dephosphorylation (and hence activation) of
      glycogen synthase. GLC8 encodes a homologue of type 1 protein phosphatase
      inhibitor-2. The genetic map positions of GLC1/IRA1, GLC3, GLC4/IRA2,
      GLC6/CIF1/TPS1 (and the adjacent VAT2/VMA2), and GLC7 were clarified. From the
      data on GLC3, there may be a suppression of recombination near the chromosome V
      centromere, at least in some strains.

PMID- 8150280
TI  - Identification and characterization of Aspergillus nidulans mutants defective in
      cytokinesis.
AB  - Filamentous fungi undergo cytokinesis by forming crosswalls termed septa. Here,
      we describe the genetic and physiological controls governing septation in
      Aspergillus nidulans. Germinating conidia do not form septa until the completion
      of their third nuclear division. The first septum is invariantly positioned at
      the basal end of the germ tube. Block-and-release experiments of nuclear division
      with benomyl or hydroxyurea, and analysis of various nuclear division mutants
      demonstrated that septum formation is dependent upon the third mitotic division.
      Block-and-release experiments with cytochalasin A and the localization of actin
      in germlings by indirect immunofluorescence showed that actin participated in
      septum formation. In addition to being concentrated at the growing hyphal tips, a
      band of actin was also apparent at the site of septum formation. Previous genetic
      analysis in A. nidulans identified four genes involved in septation (sepA-D). We
      have screened a new collection of temperature sensitive (ts) mutants of A.
      nidulans for strains that failed to form septa at the restrictive temperature but
      were able to complete early nuclear divisions. We identified five new genes
      designated sepE, G, H, I and J, along with one additional allele of a previously
      identified septation gene. On the basis of temperature shift experiments, nuclear
      counts and cell morphology, we sorted these cytokines mutants into three
      phenotypic classes. Interestingly, one class of mutants fails to form septa and
      fails to progress past the third nuclear division. This class of mutants suggests
      the existence of a regulatory mechanism in A. nidulans that ensures the
      continuation of nuclear division following the initiation of cytokinesis.

PMID- 8150281
TI  - mei-1, a gene required for meiotic spindle formation in Caenorhabditis elegans,
      is a member of a family of ATPases.
AB  - Meiotic spindle formation in the female germline of Caenorhabditis elegans
      requires expression of the gene mei-1. We have cloned mei-1 by transformation
      rescue and found that it resides near a hot spot for recombination, in an area of
      high gene density. The highest levels of mei-1 mRNA accumulate in the female
      germline of adult hermaphrodites as well as in fertilized embryos. The message
      persists for several hours after the protein functions in embryos, implying the
      need for post-transcriptional regulation. Two alternatively spliced messages are
      made that would result in proteins that differ internally by three amino acids;
      the larger of the two mRNAs is preferentially enriched in the female germline.
      The sequence of mei-1 shows that it is a member of a newly described family of
      ATPases that share a highly conserved nucleotide-binding site; four dominant
      negative mutations of mei-1 are found at or near this region. Divergent roles
      ascribed to this family include membrane function, proteolysis, transcription and
      cell cycle regulation.

PMID- 8150282
TI  - Molecular and genetic analyses of Drosophila Prat, which encodes the first enzyme
      of de novo purine biosynthesis.
AB  - The Drosophila Prat gene encodes phosphoribosylamidotransferase (PRAT), the
      enzyme that performs the first committed step of the de novo purine nucleotide
      biosynthesis pathway. Using information from amino acid sequence alignments of
      PRAT from other organisms, a polymerase chain reaction-based approach was
      employed to clone Prat. Amino acid sequence alignment of Drosophila PRAT with
      PRAT from bacteria, yeast, and vertebrates indicates that it is most identical
      (at least 60%) to the vertebrate PRATs. It shares putative amino-terminal
      propeptide and iron-binding domains seen only in Bacillus subtilis and vertebrate
      PRATs. Prat was localized to the right arm of chromosome 3 at polytene band 84E1
      2. Owing to the fact that this region had been well characterized previously,
      Prat was localized to a 30-kilobase region between two deficiency breakpoints. By
      making the prediction that Prat would have a similar "purine syndrome" phenotype
      as mutations in the genes ade2 and ade3, which encode enzymes downstream in the
      pathway, five alleles of Prat were isolated. Three of the alleles were identified
      as missense mutations. A comparison of PRAT enzyme activity with phenotype in
      three of the mutants indicates that a reduction to 40% of the wild-type allele's
      activity is sufficient to cause the purine syndrome, suggesting that PRAT
      activity is limiting in Drosophila.

PMID- 8150283
TI  - Modification of the Drosophila heterochromatic mutation brownDominant by linkage
      alterations.
AB  - The variegating mutation brownDominant (bwD) of Drosophila melanogaster is
      associated with an insertion of heterochromatin into chromosome arm 2R at 59E,
      the site of the bw gene. Mutagenesis produced 150 dominant suppressors of bwD
      variegation. These fall into two classes: unlinked suppressors, which also
      suppress other variegating mutations; and linked chromosome rearrangements, which
      suppress only bwD. Some rearrangements are broken at 59E, and so might directly
      interfere with variegation caused by the heterochromatic insertion at that site.
      However, most rearrangements are translocations broken proximal to bw within the
      52D-57D region of 2R. Translocation breakpoints on the X chromosome are scattered
      throughout the X euchromatin, while those on chromosome 3 are confined to the
      tips. This suggests that a special property of the X chromosome suppresses bwD
      variegation, as does a distal autosomal location. Conversely, two enhancers of
      bwD are caused by translocations from the same part of 2R to proximal
      heterochromatin, bringing the bwD heterochromatic insertion close to the
      chromocenter with which it strongly associates. These results support the notion
      that heterochromatin formation at a genetic locus depends on its location within
      the nucleus.

PMID- 8150284
TI  - Mosaic suppressor, a gene in Drosophila that modifies retrotransposon expression
      and interacts with zeste.
AB  - A newly identified locus in Drosophila melanogaster, Mosaic suppressor (Msu), is
      described. This gene modifies the expression of white-apricot (wa), which is a
      copia retrotransposon-induced allele of the white gene. In addition to
      suppressing wa in a mosaic fashion, this mutation suppresses or enhances the
      expression of several other retrotransposon induced white alleles. Mutations in
      Msu alter copia transcript abundance and may regulate the expression of several
      other retrotransposons. While each of the two Msu isolates is homozygous lethal,
      heteroallelic escapers occur at a low frequency. These escapers act not only as
      strong suppressors of wa, but also as a recessive enhancer of synaptic-dependent
      gene expression at white. The mutation described here suggests a connection
      between the regulation of specific transcriptional units such as retrotransposons
      and more global synapsis dependent regulatory effects.

PMID- 8150285
TI  - A member of the Notch group of interacting loci, deltex encodes a cytoplasmic
      basic protein.
AB  - Prior genetic studies have suggested a functional relationship between the
      product of the deltex gene and those of three of the so-called "neurogenic" loci,
      Notch, Delta and mastermind. To gain further insight into this relationship, we
      have proceeded with a molecular characterization of deltex. We report that deltex
      encodes a maternally and zygotically expressed transcript that conceptually
      translates to a basic protein of novel sequence. Immunolocalization of the
      protein reveals an apparently ubiquitous distribution in embryonic and imaginal
      tissues. Because our detection methods also reveal a very low level of protein
      accumulation within the cytoplasm of cells, we have used transgenic flies to
      confirm this observation by ectopically expressing deltex under the control of a
      heat shock gene promoter. The resulting overexpression rescues deltex mutant
      defects but does not produce any obvious phenotypic abnormalities in otherwise
      wild-type flies. Finally, we examine genetically several Supressor of deltex
      mutations for evidence of functional integration with deltex and other neurogenic
      genes. We demonstrate that in addition to suppressing all adult morphological
      defects of deltex alleles, these suppressors also are capable of suppressing most
      synergistic effects involving deltex and Notch, Delta and mastermind.

PMID- 8150286
TI  - The search for homology does not limit the rate of extrachromosomal homologous
      recombination in mammalian cells.
AB  - Mouse LTK- cells were transfected with a pair of defective Herpes simplex virus
      thymidine kinase (tk) genes. One tk gene had an 8-bp insertion mutation while the
      second gene had a 100-bp inversion. Extrachromosomal homologous recombination
      leading to the reconstruction of a functional tk gene was monitored by selecting
      for tk positive cells using medium supplemented with
      hypoxanthine/aminopterin/thymidine. To assess whether the search for homology may
      be a rate-limiting step of recombination, we asked whether the presence of an
      excess number of copies of a tk gene possessing both the insertion and inversion
      mutations could inhibit recombination between the singly mutated tk genes.
      Effective competitive inhibition would require that homology searching
      (homologous pairing) occur rapidly and efficiently. We cotransfected plasmid
      constructs containing the singly mutated genes in the presence or absence of
      competitor sequences in various combinations of linear or circular forms. We
      observed effective inhibition by the competitor DNA in six of the seven
      combinations studied. A lack of inhibition was observed only when the insertion
      mutant gene was cleaved within the insertion mutation and cotransfected with the
      two other molecules in circular form. Additional experiments suggested that
      homologous interactions between two DNA sequences may compete in trans with
      recombination between two other sequences. We conclude that homology searching is
      not a rate-limiting step of extrachromosomal recombination in mammalian cells.
      Additionally, we speculate that a limiting factor is involved in a recombination
      step following homologous pairing and has a high affinity for DNA termini.

PMID- 8150287
TI  - The effects of insertions on mammalian intrachromosomal recombination.
AB  - We examined the effects of insertion mutations on intrachromosomal recombination.
      A series of mouse L cell lines carrying mutant herpes simplex virus thymidine
      kinase (tk) heteroalleles was generated; these lines differed in the nature of
      their insertion mutations. In direct repeat lines with different large insertions
      in each gene, there was a 20-fold drop in gene conversion rate and only a five
      fold drop in crossover rate relative to the analogous rates in lines with small
      insertions in each gene. Surprisingly, in direct repeat lines carrying the same
      large insertion in each gene, there was a larger drop in both types of
      recombination. When intrachromosomal recombination between inverted repeat tk
      genes with different large insertions was examined, we found that the rate of
      gene conversion dropped five-fold relative to small insertions, while the rate of
      crossing over was unaffected. The differential effects on conversion and crossing
      over imply that gene conversion is more sensitive to insertion mutation size.
      Finally, the fraction of gene conversions associated with a crossover increased
      from 2% for inverted repeats with small insertions to 18% for inverted repeats
      with large insertions. One interpretation of this finding is that during
      intrachromosomal recombination in mouse cells long conversion tracts are more
      often associated with crossing over.

PMID- 8150288
TI  - The genetic basis of sex ratio in Silene alba (= S. latifolia).
AB  - A survey of maternal families collected from natural populations showed that the
      sex ratio in Silene alba was slightly female biased. Sex ratio varied among
      populations and among families within a female biased population. Crosses among
      plants from the most female biased population and the most male biased population
      showed that the sex ratio polymorphism was inherited through or expressed in the
      male parent. Males from one family in particular exhibited a severe female bias,
      characterized by less than 20% male progeny. The inheritance of sex ratio was
      investigated using a reciprocal crossing design. Sex ratios from reciprocal
      crosses were significantly different, indicating either sex-linkage or
      cytoplasmic inheritance of sex ratio. The sex ratios produced by males generally
      resembled the sex ratios produced by their male parents, indicating that the sex
      ratio modifier was Y linked. The maternal parent also significantly influenced
      sex ratio through an interaction with the genotype of the paternal parent. Sex
      ratio, therefore, is apparently controlled by several loci. Although sex ratio
      bias in this species may be due to deleterious alleles on the Y chromosome, it is
      more likely to involve an interaction between loci that cause the female bias and
      a Y-linked locus that enhances the proportion of males in the progeny.

PMID- 8150289
TI  - Frequent loss of the En transposable element after excision and its relation to
      chromosome replication in maize (Zea mays L.).
AB  - A model of En transposition during chromosome replication is presented following
      a study of somatic events associated with the transposition of En in the
      endosperm tissue of the maize kernel. Two supporting assays, the excision and the
      postexcision events, were used in following these events. The excision of the En
      transposon has been monitored in the starch-producing endosperm tissue by using
      the wx-844 autonomously mutable allele, and events after excision have been
      monitored by using various reporter alleles of the En-1 (Spm-dSpm) system. The
      initial observations revealed an unusually large amount of loss of the En
      transposon following its excision from the wx-844 allele. Subsequent analysis of
      the somatic events using the a2-m1 reporter allele to monitor the dosage of En
      suggested that the large amount of loss would result from the transposition of En
      during chromosome replication. Transposition of En from a replicated segment of
      the chromosome to another site that has also undergone replication explains most
      of the somatic events observed.

PMID- 8150290
TI  - Pairwise comparisons of mitochondrial DNA sequences in subdivided populations and
      implications for early human evolution.
AB  - We consider the effect on the distribution of pairwise differences between
      mitochondrial DNA sequences of the incorporation into the underlying population
      genetics model of two particular effects that seem realistic for human
      populations. The first is that the population size was roughly constant before
      growing to its current level. The second is that the population is geographically
      subdivided rather than panmictic. In each case these features tend to encourage
      multimodal distributions of pairwise differences, in contrast to existing,
      unimodal datasets. We argue that population genetics models currently used to
      analyze such data may thus fail to reflect important features of human
      mitochondrial DNA evolution. These may include selection on the mitochondrial
      genome, more realistic mutation mechanisms, or special population or migration
      dynamics. Particularly in view of the variability inherent in the single
      available human mitochondrial genealogy, it is argued that until these effects
      are better understood, inferences from such data should be rather cautious.

PMID- 8150291
TI  - A phylogenetic estimator of effective population size or mutation rate.
AB  - A new estimator of the essential parameter theta = 4Ne mu from DNA polymorphism
      data is developed under the neutral Wright-Fisher model without recombination and
      population subdivision, where Ne is the effective population size and mu is the
      mutation rate per locus per generation. The new estimator has a variance only
      slightly larger than the minimum variance of all possible unbiased estimators of
      the parameter and is substantially smaller than that of any existing estimator.
      The high efficiency of the new estimator is achieved by making full use of
      phylogenetic information in a sample of DNA sequences from a population. An
      example of estimating theta by the new method is presented using the
      mitochondrial sequences from an American Indian population.

PMID- 8150292
TI  - Change in genetic variance under selection in a self-fertilizing population.
AB  - In this study we show how the genetic variance of a quantitative trait changes in
      a self-fertilizing population under repeated cycles of truncation selection, with
      the analysis based on the infinitesimal model in which it is assumed that the
      trait is determined by an infinite number of unlinked loci without epistasis. The
      genetic variance is reduced not as a consequence of the genotypic frequency
      change but due to the build-up of linkage disequilibrium under truncation
      selection in this model. We assume that the order of the genotypic contribution
      from each locus is n-1/2, where n is the number of loci involved, and investigate
      the change in linkage disequilibrium resulting from selection and self
      fertilization using genotypic frequency dynamics in order to analyze the change
      in the genetic variance. Our analysis gives recurrence relations of genetic
      variance among the succeeding generations for the three cases of gene action,
      i.e., purely additive action, pure dominance without additive effect and the
      presence of both additive effect and dominance, respectively. Numerical examples
      are also given as a check on the recurrence formulas.

PMID- 8150293
TI  - Tests for major genes affecting quantitative traits in wild radish, Raphanus
      raphanistrum.
AB  - The number of gene loci coding for quantitative traits is an important issue in
      genetics. However, there are still very few empirical data on this point,
      especially in natural populations. I tested for major gene effects on ten
      quantitative traits in wild radish, using an indirect method based on the
      patterns of family means and within and between family variances for traits. This
      method should reveal whether a single locus is responsible for most of the
      variation in a trait. Eight of the traits measured were morphological dimensions
      of leaves and flowers; no strong evidence for major gene effects on these traits
      was found. In contrast, evidence for major gene effects was found in the other
      two traits, emergence time and flowering time.

PMID- 8150294
TI  - Phenotypes of lethal alleles of the recessive temperature sensitive paralytic
      mutant stambh A of Drosophila melanogaster suggest its neurogenic function.
AB  - The mutant stambhA1 (2-56.8) of Drosophila melanogaster was identified as a
      reversible temperature sensitive adult and larval paralytic. We have (i) isolated
      and analysed phenotypes of one new homozygous viable paralytic allele and two
      recessive unconditional embryonic lethal alleles of stmA and (ii) studied the
      interaction of the viable paralytic alleles with ts paralytic mutants napts1 (2
      55.2) and parats1 (1-53.9). The homozygous viable paralytic alleles stmA2 and
      stmA1 are semi dominant neomorphs. The lethal alleles stmA12 and stmA7 appear to
      be amorphs. Unhatched embryos expressing lethal stmA alleles showed hypotrophy of
      the anterior dorsal cuticle overlying the brain with a concomitant hypertrophy of
      the anterior dorsal neurogenic region (the brain). The ventral cuticle was poorly
      differentiated, and the ventral nerve chord showed mild hypertrophy and poor
      organisation. The epidermal cells in 12-13 h old embryos did not show the normal
      palisade layer arrangement. These phenotypes are similar to mutant phenotypes of
      the neurogenic class of genes whose wild type functions are necessary for
      intercellular communication. The alleles stmA1 and stmA2 do not appear to
      interact with the paralytic mutants napts1 or parats1 in double mutant
      combinations. On the basis of our results it is proposed that stmA may belong to
      the neurogenic class of genes.

PMID- 8150295
TI  - Conservation and change in structural and 5' flanking sequences of esterase 6 in
      sibling Drosophila species.

PMID- 8150297
TI  - Psychiatric symptoms in Alzheimer's disease: mental status examination versus
      caregiver report.
AB  - To examine possible reasons for conflicting prevalence data on psychiatric
      features of Alzheimer's disease (AD), we compared the results of a mental status
      examination by a physician with a questionnaire completed by caregivers in
      eliciting 12 different psychiatric symptoms in AD patients. There was agreement
      only on categories suggesting agitation. The formal examination showed more
      correlations with stage and severity of dementia than did the caregiver report.

PMID- 8150296
TI  - Hybrid dysgenesis in natural populations of Drosophila melanogaster in Japan.
      III. The P-M system in and around Japan.
AB  - The P-M system of hybrid dysgenesis in Drosophila melanogaster was investigated
      on the basis of gonadal dysgenesis, using 1,590 strains from 28 natural
      populations in Japan, and 20 populations from Southeast Asia, the Pacific area
      and Africa. Strong P strains were found sporadically in several populations in
      Japan. Few strong M strains were observed. Q strains were present at a high
      frequency in most populations. Thus, most populations in these areas were
      regarded as Q populations. The distribution of the P element and the evolution of
      P, Q and M populations are also discussed.

PMID- 8150298
TI  - Age integration and the lives of older people.
AB  - This research-based essay argues, as a stimulus to Forum discussion, that our
      currently age-differentiated society will give way to an age-integrated one. Age
      will lose its power to constrain people's entry, exit, and performance in such
      basic social institutions as education, work, and retirement. Revolutionary
      changes toward age integration are needed to reduce the "structural lag," in
      which the dynamism of human aging is outpacing the dynamism of structural change.
      To guide these changes, aging research is beginning to complement existing
      knowledge about human lives with new and deeper understanding of the social
      structures which shape and are shaped by these lives.

PMID- 8150299
TI  - Home care research: what does it tell us?
AB  - This article assesses the applied relevance of research on home care, reviewing
      the literature on predictors of use of home care services, the experience of
      receiving home care, and efficacy studies. Research to date informs us rather
      conclusively that functioning is a major predictor of use throughout the
      industrialized world, but does not inform us of the structural factors impacting
      on home care. Studies on the experience of home care, to date, have focused on
      program implementation issues, rather than more macro policy issues. Finally,
      efficacy studies by and large have not concluded that home care is less costly or
      necessarily better for the quality of life of seniors when compared with
      institutional care. This has led to questions about the raison d'etre of home
      care. We do not have longitudinal research assessing the long-term preventive
      effects of home care.

PMID- 8150300
TI  - A one-year follow-up of relaxation training for elders with subjective anxiety.

PMID- 8150301
TI  - The investigation and outcome of reported cases of elder abuse: the Forsyth
      County Aging Study.
AB  - This study summarizes the outcome of all investigations of elder abuse conducted
      in Forsyth County, North Carolina, during a 3-year period ending December 1991.
      Of the 123 cases investigated, 23 were confirmed as elder abuse. There were no
      statistically significant differences in age, sex, race, living arrangements,
      mental status, mobility, or source of report between confirmed and unconfirmed
      cases. Unconfirmed compared to confirmed cases were more likely to reside in a
      nursing home and/or to be ill. The most frequently substantiated charge was
      exploitation of resources (46%). Only 3% of charges of physical abuse were
      substantiated. Among confirmed cases, 70% were offered and accepted protective
      services.

PMID- 8150302
TI  - What's new in elder abuse programming? Four bright ideas.
AB  - This article presents four "best practice models" that address some common
      problems faced by community agencies working with elder abuse cases: a
      multidisciplinary case consultation team; a senior advocate volunteer program; a
      victim support group; and a master's of social work degree specialization in
      adult protective services. Their relatively low cost, flexibility, and level of
      success make them worthy of replication.

PMID- 8150303
TI  - Discontinuing feeding tubes in a community nursing home.
AB  - This study retrospectively reviews the experience of a 126-bed community nursing
      home at weaning tube-fed residents. All patients admitted to facility over a 6
      year period who were tube fed were included in the review (N = 15). All tube-fed
      residents had a sustained trial of oral feeding. Tube feedings were discontinued
      if oral intake was sufficient. Fifteen tube-fed patients were admitted over the
      period studied. Seven residents were retrained to eat and were weaned from tube
      feeds. We conclude that some residents admitted to our nursing home with feeding
      tubes can be weaned from them. Prospective studies using a larger sample are
      needed to better delineate the nature of the weaning process and to define the
      clinical characteristics that predict the ability to wean.

PMID- 8150304
TI  - Preventing falls among community-dwelling older persons: results from a
      randomized trial.
AB  - A randomized trial of falls prevention program that addressed home safety,
      exercise, and behavioral risks was conducted with 3,182 independently living HMO
      members age 65 and older. The intervention decreased the odds of falling by 0.85,
      but only reduced the average number of falls among those who fell by 7%. The
      effect was strongest among men age 75 and older. The likelihood of avoiding falls
      requiring medical treatment was not significantly affected by the intervention.
      We conclude that the intervention dose was not of sufficient intensity or
      duration to have a marked protective effect on older persons. Future research
      should focus on more intensive intervention approaches because serious falls do
      not appear to be amendable to low-intensity environment/behavioral efforts.

PMID- 8150305
TI  - Gender, race, and health: the structure of health status among older adults.
AB  - A previously developed model of disease, disability, functional limitation, and
      perceived health was examined for race and/or gender biases. This model focuses
      on (a) the direct effects of three factors on perceived health status, (b) how
      disability, functional limitations, and self-rated health interrelate, and (c)
      how race and gender condition these interrelationships. The results confirm the
      construct validity of separate dimensions of disability and functional
      limitation, and indicate that their differential effects are further modified by
      gender. Eight significant differences in structural effects are identified,
      including one gender effect among both blacks and whites, and seven additional
      gender effects among whites. In the structural model, then, most differences are
      gender differences among whites. The significant racial differences within gender
      were found only in the measurement model. Race differences for upper body
      disability and perceived health are consistent across gender. Sex differences,
      however, in measures of basic ADLs and household ADLs are not consistent across
      race. The findings confirm earlier conclusions that differences in the
      measurement of health exist between males and females, and between blacks and
      whites, but that the differences in the causes of perceived health exist only
      between males and females.

PMID- 8150306
TI  - How informed can consent be? New light on comprehension among elderly people
      making decisions about enteral tube feeding.
AB  - Elderly people in long-term care facilities do not understand much about various
      medical procedures, including enteral feeding. After presentation of empirically
      precise information about enteral tube feeding, residents in both long-term care
      and community-dwelling groups showed significant improvement in their
      understanding. The community-dwelling group showed even greater improvement. For
      both, comprehension was negatively related to age and depression scores, but
      positively related to IQ, reading comprehension, social support, and mental
      status. The MMSE proved the best predictor of comprehension. Implications of the
      results are discussed.

PMID- 8150307
TI  - Residential differences in the use of formal services prior to entering a nursing
      home.
AB  - The relationship between place of residence and use of formal services prior to
      entering a nursing home was examined in a sample of older persons within 30 days
      of admission. There were no residential differences in the percent reporting the
      use of formal services prior to admission. Among those who had been receiving
      services, there were no residential differences in the number of services
      received, the kinds of services used, or the average length of time services had
      been received. Residents of rural facilities were more apt to indicate that
      needed services were not available in their communities.

PMID- 8150308
TI  - Private sector hiring and use of retirees: the firm's perspective.
AB  - This article examines the hiring and utilization of retiree workers among U.S.
      firms with 20 or more employees (e.g., the hiring process, worker history with
      the company, scheduling, task assignment, relationship with other employees).
      Over 46% of private sector firms in this population hire retirees. Few firms,
      however, have a written policy or formalized program directed at hiring retirees.
      While assignment of retiree workers to regularly performed operational tasks is
      universal, the larger the firm, the more likely that a substantial proportion of
      these employees work in white-collar fields. Study results have practical
      implications for employment counseling services, private sector firms, and human
      resource specialists.

PMID- 8150309
TI  - Trends in firearm suicide among older American males: 1979-1988.
AB  - Elderly men are more likely to commit suicide than any other age group in the
      United States. Moreover, their rate of suicide steadily increased between 1979
      and 1988. National Center for Health Statistics (NCHS) Compressed Mortality data
      were used to perform an age-specific analysis of linear trends. Males 65 and over
      were the most likely to use firearms followed by those 55-64. In 1988, nearly 8
      out of 10 suicides by males 65 and over were committed with a firearm. Firearm
      related suicide rates were much lower for blacks than whites 65 and over;
      however, suicides among blacks were more likely to involve firearms than among
      whites in this age group. The authors call for a broad public policy effort
      directed at reducing the availability of firearms.

PMID- 8150310
TI  - Caregiver burden and well-being: an elusive distinction.

PMID- 8150311
TI  - Is dying young worse than dying old?
AB  - In contemporary Western society, people experience the deaths of older and
      younger persons differently. We are disposed to feel that the death of a small
      child is a greater injustice than the death of an older adult, and we experience
      correspondingly greater sorrow, anger, regret or bitterness when a very young
      person dies. This article examines these responses critically to determine
      whether they are backed by ethical considerations that reason can discern and
      defend. We contrast contemporary attitudes with those of ancient Greece and show
      the relevance that different attitudes toward death have for health care decision
      making.

PMID- 8150312
TI  - The two faces of age and the resolution of generational conflict.
AB  - The aged are often regarded as exploiters of youth, selfishly clinging to a
      disproportionate share of wealth, power, and resources. Paradoxically, they are
      also viewed as helpless victims as they fall into physical decline. These two
      faces of age appear in a number of literary texts, including works by
      Shakespeare, Balzac, and Dickens. Although these two perceptions of old age
      suggest unresolved conflict between youth and age, there often appear young
      characters in these works who mediate between these polar extremes, thus becoming
      instruments of generational continuity.

PMID- 8150313
TI  - Constraints and facilitators to friendships in late late life.
AB  - This report analyzes friendship patterns of individuals 85 and older, 77% of whom
      are women. Despite high levels of disability and the loss of age peers, the
      majority were in frequent contact with friends and still had a close friend. Over
      31 months, however, the predictors of friendship involvement changed. At Time 1,
      mood was most important, but by Time 3, increased disability was most important.
      Qualitative data describe how the constraints and facilitators lead to changing
      criteria for friendships in late late life.

PMID- 8150314
TI  - Living alone with Alzheimer's disease: effects on health and social service
      utilization patterns.
AB  - Subjects with possible or probable Alzheimer's disease who live alone are more
      likely to be women, and more likely to be poor than those living with others.
      They are also older and have milder cognitive impairments and a shorter disease
      duration. Living arrangement is a significant predictor of service utilization
      even with other factors held constant. Subjects living alone were less likely to
      use medical services such as physicians and hospitals, and more likely to use
      services such as homemaker chore and home-delivered meals. In addition, they were
      more likely to use no services than those living with others.

PMID- 8150315
TI  - Caregiver burden and generic well-being: opposite sides of the same coin?
AB  - Caregiver burden is one of the most commonly used variables in caregiving
      research, both as a predictor and as an outcome. It has been suggested that
      caregiver burden can be measured in terms of discrete dimensions of well-being
      and that burden and well-being represent opposite sides of the same coin. The
      goal of this study was to explore this issue further by comparing commonly used
      dimensions of burden with parallel dimensions of well-being, both as outcome
      variables and as predictors of other outcomes, in a sample of caregivers. The
      findings suggest that burden may tap a unique domain of caregiving outcomes that
      is not represented by more objective indicators of these effects. Dismissing
      burden as an unnecessary or redundant construct seems premature.

PMID- 8150316
TI  - Dementia management strategies and adjustment of family members of older
      patients.
AB  - Family members caring for dementia patients must often contend with a complex set
      of behavioral problems evidenced by their demented older relatives. In this study
      we examined how strategies to manage dementia problems in (N = 152) older people
      were associated with the adjustment of family members while providing assistance
      to the patient. Three Dementia Management Strategies were identified (Criticism,
      Encouragement, and Active Management) and were found to be associated with three
      indices of family members' emotional adjustment--burden, psychiatric symptoms,
      and desire to institutionalize the patient. After controlling for the influence
      of family member and patient background characteristics and family member coping,
      Dementia Management Strategies accounted for significant and unique variance in
      family members' burden and desire to institutionalize the patient but not in
      family members' psychiatric symptoms. The use of Active Management and Criticism
      was associated with greater burden, whereas use of Encouragement was tied to less
      family member burden and less desire to institutionalize.

PMID- 8150317
TI  - The anatomy and biochemistry of headache.

PMID- 8150318
TI  - Migraine: possible role of platelet insensitivity to prostaglandin E1 (PGE1).
AB  - Platelet aggregation inhibition, induced by prostaglandin E1 (PGE1), was
      evaluated in 38 patients affected by migraine. Our data indicate a complete
      insensitivity to PGE1 in these subjects. The insensitivity to PGE1 leads to
      decreased cyclic-AMP (cAMP) levels, determining an imbalance in the inhibitory
      mechanism. From this observation we can suppose that the decreased affinity of
      PGE1-receptors, causing decreased cAMP levels, may be involved in pathogenesis of
      migraine.

PMID- 8150319
TI  - SUNCT syndrome: VIII. Pupillary reaction and corneal sensitivity.
AB  - SUNCT is a newly described headache characterized by shortlasting, unilateral
      attacks of a neuralgiform character, accompanied by conjunctival injection and
      tearing on the symptomatic side. At present, 8 patients have been observed, all
      males. In the present work, vertical pupillary diameters have been estimated by
      the binocular, Whittaker infrared pupillometer (Gulf & Western). Measurements
      have been carried out both during the basal state and after topical,
      pharmacologic stimulation (by sympathicomimetic agents, i.e. tyramine (2%), OH
      amphetamine (1%) and phenylephrine (1%). In the basal state, there was no clear
      tendency to anisocoria. After sympathicomimetic drugs, there was a tendency to
      underreaction on the symptomatic side, mainly as regards the indirectly acting
      ones (OH-amphetamine and tyramine). These two agents should supposedly give
      similar results, but, nevertheless, the results partly deviated. Phenylephrine
      did not invariably normalize the symptomatic/non-symptomatic side ratio. Corneal
      sensitivity was investigated with the Cochet-Bonnet esthesiometer. Two of 6
      patients studied outside attack showed moderately lowered values on the
      symptomatic side. During attack, there seemed to be reduced corneal sensitivity
      in both patients investigated, in one bilaterally, in the other, on the
      symptomatic side only.

PMID- 8150320
TI  - Clinical and pharmacokinetic observations on valproate: a 3 year follow-up study
      in 100 children with generalized epilepsy.
AB  - The results of a 36 month observation of therapeutic effects of various schemes
      of long-term monitored treatment of primary generalized epilepsy with Valproate
      (VPA) derivatives is presented. A hundred children and adolescents aged 5-15
      constituted the experimental group. In each of 3 groups the drug was administered
      in individually assessed doses. An optimal antiepileptic clinical effect of VPA
      was achieved thanks to therapeutic monitoring, especially pharmacokinetic
      studies.

PMID- 8150321
TI  - A case of chronic cluster-like headache in a patient with cerebrovascular
      disease.
AB  - The case of a cerebrovascular patient is presented, who at the age of 70
      developed unilateral headache, localized in the left orbital region with
      radiation to the temporo-parietal homolateral region; the attacks lasted 15 to 60
      min, presented a chronic temporal pattern from their onset and were accompanied
      by homolateral lacrimation, conjunctival injection, nasal stuffiness and ptosis
      of the eyelid. The headache also presented a circadian timing with more frequent
      occurrence in the evening or early morning h. Verapamil therapy was effective.
      The possible relevance of cerebrovascular disease with respect to the late onset
      of the headache is discussed.

PMID- 8150322
TI  - Sensory and motor neuropathy caused by excessive ingestion of vitamin B6: a case
      report.
AB  - We describe a patient who developed a severe sensory and a mild motor neuropathy.
      This syndrome was due to massive and prolonged ingestion of vitamin B6 (10 g
      daily for 5 years). To our knowledge this is the first published case of motor
      neuropathy caused by chronic abuse of vitamin B6.

PMID- 8150323
TI  - Functional neurotoxicity of drugs of abuse.
AB  - The epidemic growth of the use of controlled substances has brought their toxic
      effects to clinical attention. Several drugs of abuse are known to induce nerve
      cell toxicity after acute and chronic administration. In addition, it has been
      suggested that the three main classes of abused substances, namely
      psychostimulants, ethanol and opiates, also induce changes in the function of
      discrete neural pathways. These alterations may eventually be responsible for the
      loss of behavioral control often observed during the natural history of the
      addiction process. Therefore, biochemical and behavioral toxicity deserve equal
      attention. A complex neural network within the forebrain limbic system which has
      been characterized over the past few years seems to mediate drug-seeking behavior
      and maintain drug self-administration in rodents. A striking similarity has been
      observed between this circuit and the neural substrates of motivated behavior.
      This review focuses on the possibility that drugs of abuse may acquire
      significance as reinforcers by usurping the physiological role of this circuit
      which normally operates to ensure survival of the individual. This may represent
      a subtle mechanism through which drugs of abuse may induce behavioral toxicity
      even in the absence of nerve cell loss.

PMID- 8150324
TI  - Guidelines and recommendations for the treatment of migraine. Italian Society for
      the Study of Headache (SISC).

PMID- 8150325
TI  - The Rossi orthopedic appliance: model preparation and appliance construction.

PMID- 8150326
TI  - Management of TMJ disorders in general practice.

PMID- 8150327
TI  - A rational system for the treatment of "Class I teeth" and "Class II condyles".

PMID- 8150329
TI  - Practice building through relationship marketing.

PMID- 8150328
TI  - Development of balance and harmony of the smile.

PMID- 8150330
TI  - The significance of the plane of occlusion.

PMID- 8150331
TI  - A basis for determining fees for orthodontic treatment.

PMID- 8150332
TI  - Treatment of snoring with a nocturnal airway patency appliance (NAPA).

PMID- 8150334
TI  - Epithelial cell lineages in developing, restoring, and transforming liver:
      evidence for the existence of a 'differentiation window'.

PMID- 8150333
TI  - Parasitic infections of the small intestine.

PMID- 8150335
TI  - Inflammatory mediators in the oesophagus.

PMID- 8150336
TI  - Simultaneous two level oesophageal pH monitoring in healthy controls and patients
      with oesophagitis: comparison between two positions.
AB  - For oesophageal pH monitoring, the pH probe is usually positioned 5 cm above the
      lower oesophageal sphincter (LOS). This is by convention, and has not been
      compared with other positions in its ability to discriminate between
      physiological and abnormal acid reflux. Using simultaneous two level 24 hour pH
      monitoring (5 and 10 cm above manometrically determined LOS) in 31 controls and
      51 patients with reflux oesophagitis, the significance of the precise position of
      the probe in the oesophagus was examined. Secondly, this study compared the
      discrimination between the two groups achieved at the two levels. Patients had
      greater acid exposure than controls at both levels. In controls, acid exposure
      was greater at distal than at the proximal level except the supine acid exposure,
      which was similar at both levels. In patients, acid exposure was greater at the
      distal level for all variables (median % of total time pH < 4 = 11.7 v 7.6; p =
      0.001). There was excellent correlation between the two levels for all variables
      in controls (r = 0.883, 0.935, 0.813, and p < 0.001 for percentage of time pH < 4
      for total, supine, and upright times) as well as in patients (r = 0.848, 0.848,
      0.779, and p < 0.001). On discriminant and receiver operating characteristic
      analysis, pH threshold 4 seemed as good as or better than other pH thresholds in
      discriminating between controls and patients. The percentage of total time pH
      below 4 seemed to discriminate as well or better than other variables at both
      levels. The distal level (5 cm above LOS) provided slightly better discrimination
      than proximal level (10 cm) (percentage of subjects correctly classified=81.7 v
      75.6). The critical factor for the reliability of the test is not the precise
      position of the pH probe relative to the LOS, but that the same position is
      consistently used in patients and controls.

PMID- 8150337
TI  - Prevalence of peptic ulcer in Helicobacter pylori positive blood donors.
AB  - This study aimed to determine the importance of raised antibodies to Helicobacter
      pylori in an asymptomatic population. A total of 128 asymptomatic blood donors
      who were seropositive for H pylori and consented to endoscopy were investigated.
      These subjects were from a population of 1010 blood donors screened for
      antibodies to H pylori. A questionnaire was completed to determine if any
      subjects had complained of symptoms, and they subsequently had endoscopy.
      Altogether 121 of 128 were positive for H pylori by histology and urease test
      and/or culture and all 121 had chronic active gastritis on histology. Twenty five
      of these subjects had peptic ulcer (20 duodenal, five gastric), a further 21 had
      erosive duodenitis, and two were found to have gastric cancer. H pylori
      associated peptic ulcer disease and duodenitis occur more frequently than
      previously recognised and this suggests that H pylori infection, even if
      asymptomatic, is of far greater clinical relevance than originally thought.

PMID- 8150338
TI  - High prevalence of Helicobacter pylori infection in cohabiting children.
      Epidemiology of a cluster, with special emphasis on molecular typing.
AB  - Intrafamilial cases of infection with the same strain of Helicobacter pylori (H
      pylori) have been reported but these clusters were too small to distinguish
      between person to person spread or coinfection from a common environmental
      source. To gain more information on the mode of transmission of H pylori, an
      epidemiological survey with bacterial strain differentiation by restriction
      endonuclease analysis of chromosomal DNA was carried out in an institution of 117
      children with encephalopathy (aged 3.5 to 19 years). All children with antibodies
      against H pylori had gastroscopy to obtain gastric biopsy specimens. The
      prevalence of infection (confirmed histologically or microbiologically, or both)
      was 38% (45/117), and rose to 67% in one of the five sections of the institution.
      H pylori was isolated in 34/45 cases, and 22 different strains were found of
      which five strains were present in more than one child. Up to seven children were
      infected by the same strain, five of them were living in the same section.
      Analysis of the characteristics of infected children showed the predominant role
      of living conditions and the period of time cohabiting in this unexpectedly high
      prevalence of H pylori infection in children living in good sanitary conditions.

PMID- 8150339
TI  - Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid.
AB  - The presence of ascorbic acid in gastric juice may protect against gastric
      carcinoma and peptic ulceration. This study examined the effect of Helicobacter
      pylori (H pylori) on the secretion of ascorbic acid into gastric juice by
      measuring fasting plasma and gastric juice ascorbic acid concentrations in
      patients with and without the infection and also before and after its
      eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive
      patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than
      those in 10 H pylori negative controls (median 17.8, range 5.6-155.4
      micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations
      in both groups. The median gastric juice:plasma ascorbic acid ratio in the H
      pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median
      ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the
      patients with H pylori infection there was a significant negative correlation
      between the severity of the antral polymorphonuclear infiltrate and gastric juice
      ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After
      eradication of H pylori in 11 patients, gastric juice ascorbic acid
      concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml)
      (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased
      from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high
      gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows
      active secretion of ascorbic acid into gastric juice. Secondly, H pylori
      infection causes a reversible lowering of gastric juice ascorbic acid
      concentrations, which may predispose to gastric carcinoma and peptic ulceration.

PMID- 8150340
TI  - Eradication of Helicobacter pylori with clarithromycin and omeprazole.
AB  - Clarithromycin, a new and well tolerated, acid stable macrolide antibiotic, has a
      similar antimicrobial spectrum to erythromycin but a better in vitro MIC90 (0.03
      microgram/l-1) against Helicobacter pylori (H pylori). This study aimed at
      determining the eradication rate using clarithromycin 500 mg thrice daily and
      omeprazole 40 mg daily for two weeks. Patients were given an endoscopy and H
      pylori status assessed by antral culture (microaerobic conditions, for up to 10
      days), antral and corpus histology tests (haematoxylin and eosin/Gimenez stains),
      and 13C-urea breath test (13C-UBT, European standard protocol, positive result =
      excess delta 13CO2 excretion > 5 per mil). Compliance was assessed by returned
      tablet counts. H pylori clearance at the end of treatment and eradication four
      weeks after finishing treatment were assessed by the 13C-UBT. Seventy three
      patients (54 men, median age 45 years) with duodenal ulcers (n = 42) or
      duodenitis/non-ulcer dyspepsia (n = 31) all with a positive 13C-UBT (mean (SEM)
      excess delta-13CO2 excretion = 26.6 (4.9) per mil) and either positive antral
      histology (n = 72) or positive antral culture (n = 35) were studied. Before
      treatment 2/27 (7%) isolates of H pylori were resistant to clarithromycin and
      five isolates were resistant to metronidazole. In 70/73 (96%) the 13C-UBT was
      negative immediately after finishing treatment. Four weeks later the 13C-UBT was
      negative in 57/73 (mean (SEM) excess delta 13CO2 excretion = 1.2 (0.3) per mil,
      eradication rate = 78%). Forty eight (66%) patients experienced a metallic taste
      while taking the tablets. Although four (5%) patients, however, could not
      complete the course of treatment, in only one of these four was H pylori not
      eradicated. These results show that duel therapy with clarithromycin and
      omeprazole is well tolerated. With an eradication rate of 78% it is an effective
      treatment for metronidazole resistant H pylori and may be an alternative to
      standard triple therapy.

PMID- 8150341
TI  - Abnormal intragastric distribution of food during gastric emptying in functional
      dyspepsia patients.
AB  - Although delayed gastric emptying is found in some patients with functional
      dyspepsia, there seems to be little relation between rate of emptying and
      symptoms. This study examined the hypothesis that food maldistribution rather
      than gastric stasis may equate to symptoms in such patients and used
      scintigraphic techniques to quantify the partition of gastric contents between
      proximal and distal stomach during gastric emptying. Eleven patients with
      functional dyspepsia characterised by chronic severe postprandial bloating
      without organic abnormality, and 12 healthy volunteers, ingested a standard meal
      labelled with technetium-99M (99mTc). Serial images of the gastric area in
      anterior and posterior projections were taken for 90 minutes, regions of interest
      for proximal, distal, and total stomach were defined, and activity time curves
      were derived from the geometric means of anterior and posterior counts. Total
      emptying in patients (median: 46 minutes; range: 30-76) was not significantly
      different from controls (45 minutes; 28-58) and only three showed delayed gastric
      emptying. In controls, food remained predominantly in the proximal half of the
      stomach after ingestion and then redistributed to the distal half. In the
      patients, however, initial activity in the proximal half after ingestion (48%; 40
      65) was significantly lower (p < 0.05) than in controls (60%; 39-73) and
      distributed more fully to the distal half of the stomach with a peak distal
      activity (56%; 34-58), which was consistently higher than in controls (36%; 33
      42) (p < 0.05). It is concluded that this subgroup of functional dyspepsia
      patients show abnormal intragastric distribution of food, independent of gastric
      emptying rate.

PMID- 8150342
TI  - Pharmacological modulation of gastric emptying rate of solids as measured by the
      carbon labelled octanoic acid breath test: influence of erythromycin and
      propantheline.
AB  - The *C (13C or 14C) labelled octanoic acid breath test was recently developed to
      measure the gastric emptying rate of solids. This study aimed to investigate
      whether it is sensitive enough to detect pharmacologically induced changes in the
      gastric emptying rate. Nine healthy volunteers were studied in basal condition,
      after intravenous administration of 200 mg erythromycin, and after peroral
      administration of 30 mg propantheline. Erythromycin significantly enhanced
      gastric emptying in all subjects, with an increase of the gastric emptying
      coefficient (p = 0.0043) in eight of nine and a fall in both the gastric half
      emptying time (p = 0.0020) and the lag phase (p = 0.0044) in all nine.
      Propantheline significantly reduced the gastric emptying rate, with a decreased
      gastric emptying coefficient (p = 0.0007) and an increased gastric half emptying
      time (p = 0.0168) in all subjects, but no change in the lag phase (p = 0.1214).
      Further mathematical analysis showed that breath sampling at 15 minutes intervals
      over a four hour period is recommended to guarantee accuracy and the
      discriminative value of the breath test in various gastric emptying patterns. In
      conclusion the *C labelled octanoic acid breath test is sufficiently sensitive to
      show pharmacologically induced changes of gastric emptying rates of solids.

PMID- 8150343
TI  - Polarised interleukin 8 secretion by HT 29/19A cells.
AB  - Interleukin 8 is a neutrophil chemotactic and stimulating cytokine induced by
      various inflammatory stimuli, including tumour necrosis factor, interleukin 1,
      and endotoxin. The ability of HT 29/19A enterocytes to synthesise interleukin 8
      was studied. The results show that interleukin 1 is an important stimulus for
      interleukin 8 synthesis and secretion by HT 29/19A cells, being more potent than
      tumour necrosis factor. The tumour necrosis factor and interleukin 1 induced
      interleukin 8 secretion by HT 29/19A cells was seen to be polarised according to
      the direction of stimulation. These results support the concept that mucosal
      cells (enterocytes) may play an important part in initiating mucosal
      inflammation. Furthermore, it is proposed that HT 29/19A cells constitute a tool
      to study stimulus directed polarised cytokine secretion.

PMID- 8150344
TI  - Cholesterol synthesis and high density lipoprotein uptake are regulated
      independently in rat small intestinal epithelium.
AB  - The rates of high density lipoprotein HDL uptake and cholesterol synthesis were
      compared in the normocholesterolaemic (SW) and genetically hypercholesterolaemic
      (RICO) rat intestine. The RICO rat has a hyperintestinal cholesterol synthesis.
      14C sucrose, a marker which becomes irreversibly entrapped within the cells, was
      used to measure total rat HDL uptake over 24 hours in the various cells of the
      small intestinal mucosa. The rates of sterol synthesis were estimated in vivo
      with 1-14C acetate, as previously validated. The rates of HDL uptake in the upper
      villus cells were similar along the length of the small intestine in both types
      of rat, but the rates of sterol synthesis varied up to eightfold. When the
      mucosal epithelium was divided along the villus/crypt axis, HDL uptake increased
      two to threefold and cholesterol synthesis two to fivefold in the upper villus
      compared with the crypt cells in both SW and RICO rats. The high
      cholesterogenesis in the mucosal cells of the RICO rat is not related to a
      modified HDL cholesterol uptake. Thus, cholesterol synthesis and HDL uptake seem
      to be regulated independently in the rat small intestinal mucosa.

PMID- 8150345
TI  - Lower gastrointestinal malignancy in Crohn's disease.
AB  - An increased incidence of carcinoma of the small bowel and colon has been
      described in patients with Crohn's disease. Tumours arising in the rectum and
      anus are reported less often. Between 1940 and 1992, of some 2500 patients with
      Crohn's disease seen at this hospital, 15 are known to have developed carcinoma
      of the lower gastrointestinal tract. Malignancy occurred in the colon in two
      patients, in the upper two thirds of rectum in one, in the lower third of rectum
      in seven, and in the anus in five. The 12 patients with carcinoma arising in the
      anus or lower rectum had longstanding severe anorectal Crohn's disease, which
      included a stricture in four, fistula in four, proctitis in one, abscess in two,
      and enlarged anal skin tags in one. The development of malignancy in patients
      with Crohn's disease may apply particularly to those with chronic complicated
      anorectal disease.

PMID- 8150346
TI  - Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to
      colitis.
AB  - The thickness of adherent mucus gel on the surface of colonic mucosa was measured
      in surgically resected specimens from 46 'control' patients most of whom had
      carcinoma of the colon; 12 were from right colon, 17 left colon, and 21 from
      rectum. In addition specimens were examined from 17 patients with ulcerative
      colitis and 15 patients with Crohn's disease. In controls a continuous layer of
      mucus was readily seen on specially prepared sections viewed by phase contrast
      illumination. Mean values for right and left colon and rectum were 107 (48), 134
      (68), and 155 (54) microns respectively with a significant difference between
      right colon and rectum (p = 0.015). Values in ulcerative colitis showed greater
      variation and in those areas with acute inflammation mucosa was denuded of the
      mucus layer. In contrast, values for Crohn's disease were normal or greater than
      normal in thickness--right colon 190 (83) microns compared with 107 48 microns, p
      = 0.0093. A series of validation experiments are described for the method used to
      measure mucus thickness. The possible role of mucus in the pathogenesis of
      inflammatory bowel disease is discussed.

PMID- 8150347
TI  - Frequency of glucocorticoid resistance and dependency in Crohn's disease.
AB  - The outcome of the first steroid treatment course was prospectively studied in a
      regional cohort of 196 patients with Crohn's disease diagnosed 1979-1987. The
      immediate outcome after 30 days, and the prolonged outcome 30 days after
      treatment had stopped, are described. In all 109 patients treatment was analysed.
      Complete remission was obtained in 48%, partial remission in 32%, and no response
      in 20% within 30 days of treatment. Among primary responders (complete and
      partial remission), 55% remained in prolonged response after treatment had
      finished, while 45% relapsed or could not be withdrawn from treatment within one
      year. Localisation of disease, age, sex or clinical symptoms did not
      significantly correlate with outcome, which can be summarised as prolonged
      steroid response in 44%, steroid dependency in 36%, and steroid resistant in 20%
      of the patients.

PMID- 8150348
TI  - Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's
      disease.
AB  - One hundred and thirty patients with active symptoms of Crohn's disease were
      treated in a double blind randomised controlled trial with rifampicin, isoniazid,
      and ethambutol, or identical placebos for up to two years. All other treatment
      considered necessary was continued. Analyses were based on 126 patients, 63 in
      each treatment group. Thirty seven in the active and 30 in the placebo group had
      previous surgical procedures. There was no difference in concomitant treatment
      between the two groups. Thirty in the active and 46 in the placebo groups were
      taking corticosteroids at entry to the trial. Forty eight of 63 patients in the
      active and 49 of 63 in the placebo group, completed at least 12 months' therapy.
      Reasons for early withdrawal included pregnancy, adverse reaction, and failure to
      comply. There was no significant difference in the mean number of months
      completed between the two groups. Nineteen adverse reactions were recorded for 17
      patients in the active group compared with three reactions in patients on
      placebo. All of the nine patients withdrawn early because of adverse reactions
      were in the active group. Fifteen patients on active treatment and 14 on placebo
      had surgery during the trial with no difference in the type of surgery required
      between the groups. Radiological assessments based on 98 patients at the end of
      the trial showed no significant differences between groups in changes of extent
      of disease. More patients developed strictures on placebo compared with active
      treatment but without a statistically significant difference. No differences were
      found between groups for the total prednisolone dose or the number of days on
      which prednisolone dose was 10 mg or above. Serial measurements of body weight
      and Crohn's disease activity index (CDAI) together with blood values for albumin,
      haemoglobin, white cell count, and platelets showed no consistent different
      differences between groups. There were occasional significant differences for
      some of these values between groups, which were not sustained. The trail provides
      little evidence of tangible benefit from the trail treatment.

PMID- 8150349
TI  - Incidence of inflammatory bowel disease in north west Greece: rarity of Crohn's
      disease in an area where ulcerative colitis is common.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) are generally regarded as
      diseases of affluent societies of the Western World, although their frequency in
      less affluent areas is not well established. This retrospective study therefore,
      assesses the incidence of UC and CD in a semirural area of north west Greece
      during the 10 year period 1982-1991. By the 31 December 1991, 61 patients had met
      standard diagnostic criteria for UC (annual incidence 4.0/10(5), 95% confidence
      intervals 3.0 to 5.0/10(5)) and only five patients met the diagnostic criteria
      for CD (annual incidence 0.3/10(5), 95% confidence intervals 0.1 to 0.8/10(5)) in
      this area of 157,214 inhabitants. UC incidence was lowest in the first three
      years at 1.8/10(5) per annum and subsequently increased to 4.8 and 5.1/10(5) per
      annum for the successive four and three year periods respectively. UC incidence
      was slightly higher in men. A third of all cases of UC had pancolitis while a
      quarter had only proctitis. More than one half were categorised as having
      moderate or severe colitis. Three quarters of the patients resided in urban
      areas. The incidence of CD was a twelfth of the UC incidence, which is in
      considerable contrast with most Western countries where the incidence of CD is
      usually no less than a third that for UC. The rarity of CD points to the absence
      of aetiological environmental factors specific for CD.

PMID- 8150350
TI  - Ileitis after colectomy for ulcerative colitis or carcinoma.
AB  - An ileitis developing years or months after ileostomy was recognised and
      described many years ago but has rarely been mentioned since. We describe nine
      patients with a non-specific preanastomotic ileitis that developed years after
      colectomy in patients operated on for ulcerative colitis or carcinoma. The
      disease developed after various types of reconstruction: ileorectal, ileoanal,
      with or without pouch. The diseased ileum showed inflammation, erosions,
      ulcerations, and sometimes strictures. The disease course ranged from
      asymptomatic to severe pain and diarrhoea. No specific cause could be shown.
      Granulomas, infectious agents or ischaemic changes were not found. The
      anastomosis was always patent. Three patients have had numerous episodes of
      intestinal obstruction presumably because of adhesions. Seven of nine patients
      were female. The response to steroids, 5-aminosalicylic acid preparations, and
      methotrexate was poor, three patients responded well to azathioprine. The
      condition is not rare and the cause remains unknown.

PMID- 8150351
TI  - Desmoid tumours in familial adenomatous polyposis.
AB  - Desmoids are rare, benign fibromatous lesions, which can arise in patients with
      familial adenomatous polyposis (FAP), a disorder caused by germline adenomatous
      polyposis coli (APC) gene mutation. This study investigated the risk of desmoids
      in FAP, the relation between specific APC gene mutations and desmoid formation,
      and the clinical characteristics of FAP patients with desmoids. Eighty three of
      825 FAP patients (10%) from 49 of 161 kindreds (30%) had desmoids. The absolute
      risk of desmoids in FAP patients was 2.56/1000 person years; comparative risk was
      852 times the general population. APC gene mutations were similar in families
      with and without desmoids. The female/male ratio was 1.4 (p = NS). Previous
      abdominal surgery was noted in 68% of patients with abdominal desmoids (55%
      developed within five years postoperatively). Desmoid risk in FAP family members
      of a desmoid patient was 25% in first degree relatives v 8% in third degree
      relatives. Desmoids are a comparatively common complication of FAP associated
      with surgical trauma and familial aggregation. Desmoid development was not linked
      to specific APC gene mutations and was not found predominantly in women. Studies
      of chemopreventive therapy, given within five years after abdominal surgery,
      should be considered in FAP patients with a family history of desmoid disease.

PMID- 8150352
TI  - Human colorectal tumour infiltrating lymphocytes express activation markers and
      the CD45RO molecule, showing a primed population of lymphocytes in the tumour
      area.
AB  - This study investigated the phenotype of freshly isolated human tumour
      infiltrating lymphocytes (TIL) from 14 patients with colorectal tumours, and
      compared them with lymphocytes derived from the lamina propria of the unaffected
      mucosa and with lymphocytes derived from peripheral blood of the same patients.
      It was found that TIL expressed the activation markers CD25 and HLA-DR to a
      higher extent than the peripheral blood lymphocytes (p = 0.01), and that both
      lamina propria lymphocytes and TIL preferentially expressed the CD45RO +
      phenotype, associated with memory cells, in contrast with peripheral blood
      lymphocytes [corrected]. Both lamina propria lymphocytes and TIL contained few
      natural killer (NK) cells (CD3-CD56+) compared with peripheral blood lymphocytes
      (p = 0.001), and this was reflected in the cytotoxicity assays. After 1 to 2
      weeks in culture with interleukin-2 100 U/ml, lymphocytes from all three
      compartments had a high cytolytic activity against all targets tested, consistent
      with the lymphokine activated killer cell phenomenon. No increase in the number
      of NK cells was noted after culture, but 20-30% of the T cells now coexpressed
      the CD56 molecule. This was most prominent in the CD8+ subset, but lymphokine
      activated killer cell activity was found in both CD4+ and CD8+ subsets. Possible
      tumour escape mechanisms are discussed.

PMID- 8150353
TI  - Pelvic floor function in multiple sclerosis.
AB  - The aim of this study was to define pelvic floor function in patients with
      multiple sclerosis and bowel dysfunction, either incontinence (MSI) or defecation
      difficulties without incontinence (MSC). Normal controls and patients with
      idiopathic neurogenic faecal incontinence without multiple sclerosis (FI, disease
      controls) were also studied. Thirty eight multiple sclerosis patients (20
      incontinent, 18 incontinent) 73 normal controls, and 91 FI patients were studied.
      The FI group showed the characteristic combined sensorimotor deficit previously
      described in these patients of low resting and voluntary contraction and
      pressures, increased sensory threshold to mucosal stimulation, and increased
      pudendal nerve terminal motor latencies and fibre densities. MSI patients had
      significantly lower anal resting pressures (80 (30-140) cm H2O, median (range) v
      98 (30-200), normal controls, p = 0.002) and both MSC and MSI patients had
      significantly lower anal maximum voluntary contraction pressures (65 (0-260) cm
      H2O, MSC and 25 (0-100), MSI v 120 (30-300), normal controls, p = < 0.0004) and
      higher external anal sphincter fibre densities (1.7 (1.1-2.6), MSC and 1.7 (1.1
      2.4), MSI v 1.5 (1.1-1.75), normal controls, p < 0.006) compared with normal
      controls but pudendal nerve terminal motor latencies were similar and no sensory
      deficit was found. This contrasted with the idiopathic faecal incontinent
      patients who, in addition to significantly higher fibre densities (1.8 (1.1-3), p
      = 0.001) had increased pudendal latencies (2.5 (1.1-5.5) mS v 2.08 (1.4-2.6), p =
      0.001) compared with normal controls. The idiopathic faecal incontinent group had
      significantly lower resting anal pressures (50 (10-160) cm H2O, p=0.02) than the
      MSI group. Comparison with the incontinent and continent multiple sclerosis
      groups showed that incontinence was associated with lower voluntary anal
      contraction pressures (25 (0-100) v 65 (0-260), p=0.03) but that there were no
      other differences between these two groups. Pelvic floor function is considerably
      disturbed in multiple sclerosis, showing muscular weakness with preservation of
      peripheral motor nerve conduction, providing indirect evidence that this is
      mainly a result of lesions within the central nervous system.

PMID- 8150354
TI  - Fistulas in ano: endoanal ultrasonographic assessment assists decision making for
      surgery.
AB  - Eighteen patients with a clinical impression of a complex fistula in ano, had
      anal endosonography to delineate the anatomy of the fistula track and identify
      associated areas of sepsis. The clinical impression of a complex fistula was
      refuted by endosonography and subsequent surgical exploration in two cases.
      Horseshoe tracks were identified in nine (50%) patients and fluid collections,
      not evident on clinical examination were identified in eight (45%) patients.
      Accurate identification of the internal opening with a 7 MHz transducer was
      possible in two (11%) cases. External sphincter damage was evident in four (22%)
      patients. Surgical findings matched endosonographic appearances in all but one
      case (94%). Anal endosonography is an accurate and minimally invasive method of
      delineating the relation of fistula tracks to the anal sphincters and identifying
      deep areas of sepsis in relation to such fistulas.

PMID- 8150355
TI  - Focused liver ablation by cavitation in the rabbit: a potential new method of
      extracorporeal treatment.
AB  - A new device was used to achieve focused tissue ablation by shockwave induced
      cavitation. The device produced a half cycle of negative pressure followed by a
      shock wave, thus enhancing cavitation. Twenty eight New Zealand rabbits were
      treated. Therapeutic ultrasound was targeted at the centre of the liver under
      ultrasound guidance. The focal volume was scanned with a computer operated x-y-z
      micropositioner. The number and frequency of bursts as well as the distance
      between two x-y-z displacements were preselected. The relation of tissue ablation
      seen to preselected parameters, effects on surrounding tissues, biological side
      effects, and mode of healing were studied. Macroscopy, planimetry, and
      quantitative microscopy were used. Focused and homogeneous tissue ablation was
      achieved within well defined limits. Maximal tissue ablation was seen in the
      centre of the target. Liver surrounding the target remained unaffected. Lesions
      were made of a-cellular spots surrounded by disorganised rims of necrotic
      hepatocytes; 24 hours after treatment, the changes (mean (SEM)) in alanine
      transaminase and haemoglobin were +225 (36)% and -2.4 (2)% respectively. Serum
      transaminases, haemoglobinaemia, and packed cell volume were normal 21 days after
      treatment and the target area was replaced by a fibrous scar. It is concluded
      that ultrasound cavitation may achieve extracorporeal intrahepatic tissue
      ablation inside a predetermined target. This technique should now be tested in an
      animal hepatic tumour model.

PMID- 8150356
TI  - Oxygen saturation during endoscopic retrograde cholangiopancreatography: a
      comparison of two protocols of oxygen administration.
AB  - Patients having endoscopic retrograde cholangiopancreatography (ERCP) are
      generally elderly and require sedation while in the prone position. These factors
      may be expected to aggravate any risk of arterial hypoxia. This study evaluated
      two protocols of oxygen administration, one with and one without pre-oxygenation.
      In 25 patients in whom pre-oxygenation with 4 litres/minute for five minutes
      before sedation was used, followed by continuous oxygen administration, arterial
      oxygen saturation did not fall below 90% at any stage during the procedure. By
      contrast, in 25 patients who were not pre-oxygenated oxygen saturation fell below
      90% in nine (36%). As expected, hypoxia occurred most frequently during the early
      stages of sedation and endoscope insertion. Hypoxia did not occur in association
      with operations such as sphincterotomy, stone extraction or stent insertion. This
      study confirms that arterial hypoxia is a common event during ERCP and can be
      completely prevented by pre-oxygenation with four litres of oxygen given
      intranasally for five minutes before sedation.

PMID- 8150357
TI  - Non-adrenergic non-cholinergic inhibitory innervation shown by electrical field
      stimulation of isolated strips of human gall bladder muscle.
AB  - Non-adrenergic non-cholinergic (NANC) inhibitory nerves have been described in
      all regions of the gastrointestinal tract, but have not been shown previously in
      the human gall bladder. Electrical field stimulation was used in the presence of
      various agonists and antagonists to show NANC inhibitory innervation in strips of
      human gall bladder muscle. Gall bladder strips were set up isometrically in an
      organ bath containing oxygenated Krebs's solution. Electrical field stimulation
      was applied at 10 Hz, pulse width 0.3 ms and supramaximal voltage at intervals of
      3 to 5 minutes. Of 60 strips that contracted in response to electrical field
      stimulation, 30 showed relaxation on electrical field stimulation in the presence
      of either carbachol (5-10 microM) or else atropine (0.5-2 microM) plus
      cholecystokinin octapeptide (0.01-0.1 microM) or caerulein (0.1 nM) or histamine
      (5-10 microM). In 22 strips this relaxation was not abolished by guanethidine (2
      5 microM) showing the NANC nature of this response. The NANC relaxation was
      abolished by L-nitroarginine (100 microM) and this effect was partly reversible
      by L arginine (200 microM). All responses to electrical field stimulation were
      abolished by tetrodotoxin (0.2-2 microM). These results show for the first time a
      NANC inhibitory innervation in human gall bladder muscle. The probable
      neurotransmitter is nitric oxide.

PMID- 8150358
TI  - Pulverisation of calcified and non-calcified gall bladder stones: extracorporeal
      shock wave lithotripsy used alone.
AB  - Using a modified electromagnetic lithotripter (Siemens), extracorporeal shock
      wave lithotripsy (ESWL) was performed in 260 patients with gall bladder stones.
      Exclusion criteria for treatment were a non-functioning gall bladder, subcostal
      gall bladder location, and multiple stones occupying more than three quarters of
      the gall bladder volume. Stone pulverisation was the end point of ESWL. The
      number of shock wave discharges and sessions was not limited. Pulverisation was
      achieved in 250 patients (96.1%) after a median of three ESWL sessions (range 1
      21). The number of sessions required depended upon stone composition and burden.
      More than three sessions were required in 60.2% of patients with calcified stones
      compared with 35.9% of patients with non-calcified stones (p < 0.001). 65.8% of
      patients with stones measuring more than 30 mm in total diameter required more
      than three sessions compared with 42.9% of patients with a stone burden less than
      30 mm (p < 0.01). At 18-24 (8-12) months follow up, stone clearance was achieved
      in 94.3% (80.4%) of patients with non-calcified stones, compared with 89.5%
      (76.8%) in patients with calcified stones and in 75% (71.4%) of patients with a
      total stone diameter more than 30 mm compared with 95.7% (80.4%) for patients
      with a total stone diameter less than 30 mm (p < 0.05). ESWL related
      complications (gross haematuria) occurred in three patients. Thirty six (13.8%)
      patients experienced biliary colic; four had cholecystectomy, and five endoscopic
      papillotomy because of common bile duct obstruction. Stone recurrence was seen in
      5.3% of patients over a follow up period of up to two years (median 16.6 months).

PMID- 8150359
TI  - Benign intracranial hypertension during prednisolone treatment for inflammatory
      bowel disease.
AB  - Benign intracranial hypertension (BIH, pseudotumour cerebri) is a rare condition
      with unknown aetiology although hormonal influences have been implicated. It
      occurs spontaneously, particularly in young obese women, and is associated with
      several drug treatments including corticosteroids. Two young adult women are
      described in whom headache and papilloedema in association with raised
      intracranial pressure occurred during prednisolone treatment for inflammatory
      bowel disease. This provides further evidence of the risk of BIH during
      corticosteroid treatment and has not been described before in adults with this
      condition. Advice is given to gastroenterologists to use corticosteroids with
      caution in adults, particularly young, fertile female patients. The treatment of
      a severe relapse of colitis in a patient who has had one episode of steroid
      related BIH remains a dilemma.

PMID- 8150360
TI  - Drug induced lymphocytic colitis.
AB  - Three cases are presented of lymphocytic colitis with chronic diarrhoea
      concurrent with longterm use of Cyclo 3 Fort, a phlebotonic drug used in France.
      The histological and immunopathological features of lymphocytic colitis are
      described. We show that lymphocytic colitis is drug induced, particularly in one
      patient where the immunopathological features of mucosal immune cell activation
      were induced by drug rechallenge. It is concluded that lymphocytic colitis may be
      drug induced, secondary to a chronic activation of the mucosal immune system by
      one or several components of the drug.

PMID- 8150361
TI  - Painful rib syndrome.

PMID- 8150362
TI  - Painful rib syndrome.

PMID- 8150363
TI  - Colonoscopic surveillance in ulcerative colitis.

PMID- 8150364
TI  - Endocrine features in eutestosteronemic women with polycystic ovaries.
AB  - We attempted to assess the association between hyperandrogenemia and
      inappropriate gonadotropin secretion in women with polycystic ovaries (PCO).
      Thirty-one patients diagnosed as PCO by ultrasonography were divided into two
      subgroups: 17 with high serum total testosterone (T) level (> or = 0.5 ng/ml) and
      14 with normal serum total T level (< 0.5 ng/ml). Both subgroups presented for
      the complaints of oligomenorrhea and/or hirsutism. The control group consisted of
      15 women with regular ovulation for reference data collection. The PCO subjects
      with normal T, but not those with high T, revealed remarkable depletion of sex
      hormone binding globulin (SHBG), as compared with control. The PCO subject groups
      with high and normal serum T did not differ with respect to estrogen level,
      androgen level, follicle-stimulating hormone and prolactin levels, and SHBG
      concentration. Solely serum luteinizing hormone (LH) level was observed to be
      higher in those with high T, as typical features, than another subgroup or
      control. These data suggest that an increase in bioactive T as a result of
      decrease in serum SHBG or LH elevation may contribute to ovarian dysfunction in
      the patient with PCO.

PMID- 8150365
TI  - Detection of anti-Candida albicans IgE antibodies in vaginal washes from patients
      with acute vulvovaginal candidiasis.
AB  - Vaginal washes from 55 women were investigated by means of an ELISA method for
      the presence of IgE antibodies against Candida albicans. These antibodies were
      detected in 87.1% of patients with clinical acute vulvovaginal candidiasis (group
      I), 100% of patients with suspected vulvovaginal candidiasis but negative by
      microscopy and culture (group II), 0% of asymptomatic carriers (group III) and
      33.3% of uninfected controls (group IV). Statistically significant differences
      were observed comparing groups I and II vs. groups III and IV. The highest IgE
      vaginal antibody titers were mostly at the expense of serotype A C. albicans
      strains, which represented 83.3% of the C. albicans isolates. Non-C. albicans
      species also showed very low IgE levels. No correlation between serum and vaginal
      IgE was found. Furthermore, a second determination of vaginal IgE levels was
      performed in 3 patients. A decrease in IgE levels concomitant to a decline in
      clinical symptoms was observed in all of them after treatment.

PMID- 8150366
TI  - Comparison of cefonicid and cefazolin prophylaxis in abdominal hysterectomy.
AB  - One hundred and sixty-four patients undergoing abdominal hysterectomy for benign
      diseases were prospectively evaluated. The efficacy and safety of surgical
      prophylaxis with a single dose of the long-acting cefonicid was compared to the
      standard three dose regimen of cefazolin. Prophylaxis was successful in 82 of 85
      (96.5%) patients receiving cefonicid and in 77 of 79 (97.5%) patients receiving
      cefazolin. No serious adverse effects were encountered with both drugs. It is
      concluded that single dose intravenous cefonicid, when given preoperatively, is
      as safe and effective as the standard multiple dose regimen of cefazolin in
      patients undergoing elective abdominal hysterectomy.

PMID- 8150367
TI  - Histopathological aspects of pelviscopic hysterectomy. Investigation of
      histological giant sections and morphometry to confirm a new application of
      minimally invasive surgery.
AB  - The present study attempts to confirm the effectiveness of a new method of
      pelviscopic hysterectomy which maintains the pelvic floor integrity comparable to
      that in a supracervical uterus amputation. A major advantage of this procedure is
      that the central portion of the cervix and transformation zone is punched out
      using a special resection tool for the purpose of removing any potential source
      of cancer. Thirty-four specimens resected by pelviscopic hysterectomy were
      investigated using histological giant and serial sections. Morphometrical
      analysis was performed using MOP-AMO2 (Kontron Instruments). The transitional
      zone and cervical glands were excised completely with an average security
      distance of 1.5 cm to the resection margins. No mesonephric remnants were found
      which might serve as a possible source of adenocarcinoma. Our study confirms that
      the application of this new technique of pelviscopic hysterectomy is not limited
      by the development of stump carcinoma while also possessing the additional
      advantage of maintaining pelvic floor integrity.

PMID- 8150368
TI  - Immunohistochemical detection of proliferating tumor cells in cervical cancer
      using monoclonal antibody Ki-67.
AB  - Monoclonal antibody Ki-67 identifies cells in G1, S, G2, and M phases of the cell
      cycle. In this cytokinetic study, Ki-67 was used to characterize tumor cells in
      human cervical cancer specimen. This immunohistochemical study showed that Ki-67
      staining gave a brown nuclear reactivity dispersed heterogeneously in a tumor
      cell population and correlated well with the mitotic activities of tumor cells.
      The finding suggested that Ki-67 staining provides an easily countable index for
      the study of proliferating cell populations in cervical cancer.

PMID- 8150369
TI  - Treatment of precursors of endometrial cancer.
AB  - From 1985 to 1991, 73 hysterectomies were performed on patients suffering from
      histologically demonstrated adenomatous hyperplasia, grades 1-3, at the Kiel
      University Hospital of Gynecology. The operations were done within a month from
      the diagnosis. Three of the patients were under 40 years of age. An exact
      correspondence between the grade of adenomatous hyperplasia in the abraded
      material and the uterus specimen was found in only 44% of the cases. In the
      patients over 40 with adenomatous hyperplasia of any grade demonstrated in the
      abraded material, an already well-differentiated endometrial carcinoma was found
      in 16% of the cases, while such a carcinoma was found in 57% of the cases with
      grade 3 adenomatous hyperplasia! Even though drug therapy with gestagen may have
      a beneficial effect, a hysterectomy is nevertheless the treatment of choice for
      adenomatous hyperplasia of grade 2 and grade 3 in patients over 40 because it is
      not absolutely certain from a diagnostic point of view that the material is
      representative of the entire mucosa. In women under 40 years of age it is
      necessary to plan therapy on an individual basis.

PMID- 8150370
TI  - Plasma prealbumin in women with epithelial ovarian carcinoma.
AB  - BACKGROUND: Epithelial ovarian carcinoma produces steroid hormones that may be of
      prognostic importance. The steroids are mainly bound to plasma albumin and sex
      hormone-binding globulin. Alterations in plasma protein levels influence hormonal
      effects. As plasma prealbumin may reflect changes in the patient's clinical
      status better than do albumin determinations, it is of interest to analyze
      prealbumin in patients with ovarian cancer. METHODS: Fifty-one postmenopausal or
      oophorectomized women with epithelial cancer of the ovary were studied. Plasma
      prealbumin was analyzed prior to and during chemotherapy. Tumor volumes were
      evaluated and blood samples were drawn for prealbumin analysis on four occasions
      at monthly intervals. Plasma levels were compared with one control group of
      postmenopausal women, one group of fertile women in the follicular phase of the
      menstrual cycle, and one control group of postmenopausal women with
      nongynecologic disseminated malignant disease. RESULTS: Prealbumin concentrations
      are lower in women with carcinoma of the ovary than in postmenopausal controls
      and the levels correlate inversely to tumor volume. Prealbumin concentrations are
      decreased in the large tumor group, advanced tumor stage group and in the control
      group with nongynecologic disseminated malignant disease. During chemotherapy,
      plasma prealbumin increases concomitantly with the reduction of tumor volume.
      Initial plasma prealbumin concentration seems to have prognostic importance.
      CONCLUSIONS: Prealbumin may be a sensitive indicator of disturbances in protein
      metabolism. It may reflect changes in the patient's clinical status better than
      do albumin determinations. Prealbumin concentration seems to have a prognostic
      importance in women with epithelial ovarian carcinoma. CONDENSATION: Prealbumin
      is studied in women with epithelial ovarian carcinoma prior to and during
      chemotherapy, and is found to vary inversely with changes in tumor volume.

PMID- 8150371
TI  - Frequent overexpression of p53 in dysgerminoma of the ovary.
AB  - The expression of p53 in 7 dysgerminomas of the ovary was investigated
      immunohistochemically with the monoclonal antibodies DAKO-p53/Do-7 and Dianova
      p53/Do-1. All the tumors exhibited overexpression of p53 protein. Immunoreactive
      tumor cell nuclei amounted to more than 50% in 2 tumors, 10-50% in 2 tumors, and
      less than 10% in 3 tumors. No relationship was found between tumor stage and the
      degree of p53 expression. Overexpression of p53 thus appears to be very common in
      dysgerminoma, as it is in epithelial ovarian cancer.

PMID- 8150372
TI  - Highly elevated CA125 and tubo-ovarian abscess mimicking ovarian carcinoma.
AB  - Elevated serum CA125 levels may be caused by any condition which produces
      peritoneal irritation as well as by the presence of various malignancies. This
      report of a case with atypical presentation of tubo-ovarian abscess and CA125
      level of 1,160 U/ml serves to re-emphasize cautious operative planning in
      patients desirous of reproductive capability in the face of findings highly
      consistent with probable malignancy. This is the highest reported serum CA125
      level in a reproductive age woman with well-documented reversible benign disease.

PMID- 8150373
TI  - Early pregnancy factor as a marker for assessing embryonic viability in
      threatened and missed abortions.
AB  - It is now well recognized that the presence of early pregnancy factor (EPF) can
      signify the occurrence of fertilization, continuation of pregnancy and the
      existence of a viable embryo. With this in view, a study was undertaken to
      observe the potential of EPF as a marker in assessing embryo viability in cases
      complicated with vaginal bleeding during early pregnancy. The results indicated
      that the sensitivity of EPF as a marker in predicting threatened or missed
      abortion was 78.9% and the specificity 95.6%. The positive predictive value was
      observed to be 93.8% and the negative predictive value 84.6%. Our studies have
      shown that since EPF is present in viable but absent in non-viable pregnancies,
      it could be a useful marker of prognostic value in threatened abortions.

PMID- 8150374
TI  - Modulation of amnionic adenylate cyclase and cAMP phosphodiesterase by
      prostaglandins E1 and F2 alpha.
AB  - The action of prostaglandins E1 and F2 alpha on adenylate cyclase and cAMP
      phosphodiesterase was assayed in cell membrane fractions of amnion obtained
      before and after labor from term physiological pregnancies. Both prostaglandins
      stimulate the activity of adenylate cyclase in a dose-dependent manner. After
      spontaneous delivery both prostaglandins stimulate the activity of
      phosphodiesterase at lower doses and inhibit it at higher ones while the
      stimulatory effect of low doses is missing before labor. Such a behavior could
      represent a mechanism for the preservation of the cAMP-mediated processes
      throughout the entire event of delivery.

PMID- 8150375
TI  - Parathyroid hormone-related protein during pregnancy and the perinatal period.
AB  - To evaluate whether parathyroid hormone-related protein (PTHrP) plays any role in
      calcium metabolism during pregnancy and the perinatal period, we measured
      parathyroid hormone (PTH), immunoreactive PTHrP and calcium in maternal serum of
      women during pregnancy and puerperium, and in maternal and cord serum at
      delivery. Serum PTH levels in pregnant women were lower than those in nonpregnant
      women (p < 0.01). However, serum PTHrP levels were similar in the two groups of
      women. Cord serum total and ionic calcium levels were higher, and cord serum PTH
      levels were lower compared to maternal values (p < 0.01). Cord serum PTHrP levels
      were higher than maternal values, and umbilical arterial levels were higher than
      umbilical venous levels (p < 0.01). Higher levels of PTHrP in umbilical arterial
      blood than in umbilical venous blood suggest that the main source of cord blood
      PTHrP may be the fetus. PTHrP is reported to stimulate placental calcium transfer
      from mother to fetus in animals. The elevated cord blood PTHrP level in
      association with the decreased PTH level suggests that stimulation of placental
      calcium transfer by PTHrP may also be operative in humans.

PMID- 8150376
TI  - HLA antigen sharing in preeclampsia.
AB  - The association between human leukocyte antigens (HLA) and the development of
      preeclampsia (PE) was studied in 48 women with PE and their partners. In 20 of
      the families, the HLA antigens of the child were also determined. In 8 of 15
      cases (53%) of primigravidae with PE, the child shared at least 2 paternal
      antigens with the mother, whereas this was the case in only 1 of 26 (4%) children
      of healthy mothers (p < 0.001). In contrast to this, none of 6 children of
      multigravidae with PE shared 2 paternal antigens with the mother. An increased
      homozygosity at the HLA-B locus was also seen in the children of primigravidae
      with PE (40 vs. 4%, p = 0.01).

PMID- 8150377
TI  - Oligohydramnios: maternal complications and fetal outcome in 145 cases.
AB  - One hundred and forty-five cases of oligohydramnios in the second and third
      trimester were diagnosed by ultrasonography out of 25,000 obstetrics patients
      (0.58%). In this group, pregnancy complications included hypertension (22.1%) and
      bleeding in the second trimester (4.1%). We found a high incidence of meconium
      stained amniotic fluid (29.1%), fetal distress (7.9%) and premature placental
      separation (4.2%). IUGR occurred in 24.5% of cases. Asphyxia during labor
      occurred in 11.5% and different other perinatal problems in 23.5%. Cesarean
      section was performed in 35.2% of these pregnancies. Seventeen percent of the
      cases presented as breech. Intrauterine fetal death occurred in 5.5% of these
      pregnancies. The gross perinatal mortality was 16% and the corrected perinatal
      mortality was 10.7%. The overall rate of fetal malformations was 11% and that of
      lethal malformations 4.8%. The skeletal (7.6%) and urinary system (4.1%) were the
      predominant systems affected. Oligohydramnios is associated with a higher rate of
      pregnancy complications and increased fetal morbidity and mortality, and thus
      termination should be considered when pulmonary maturity is present or in cases
      of fetal distress.

PMID- 8150378
TI  - Fetal circulatory system in growth-retarded fetus with late decelerations and
      oligohydramnios.
AB  - We present 4 cases of growth-retarded fetuses with fetal heart rate late
      decelerations and oligohydramnios. Doppler ultrasound revealed significantly
      decreased pulsatility index (PI) values of the middle cerebral artery; however,
      the PI values of the renal artery, femoral artery and umbilical artery were
      within normal ranges in all fetuses. Relative redistributions in the fetal
      circulatory system were shown with fetal hypoxemia without acidosis.

PMID- 8150379
TI  - A semiquantitative rat model for intraperitoneal postoperative adhesion
      formation.
AB  - A reproducible and semiquantitative rat model for the evaluation of therapeutic
      modalities used for the prevention of postoperative adhesion formation is
      designed within three experiments. In all experiments, a standard peritoneal
      defect was excised, sutured and adhesion formation was evaluated after 2 weeks
      according to the extent. Variation in extent of adhesions and type of tissue
      involved depended on the experimental design. While neither cecum nor colon
      descendens participated in the adhesions after a clamping trauma, the uterine
      horn was found to participate in almost all cases, especially when sutured
      proximally and distally to the peritoneal defect. The peritoneal defect/uterine
      horn model proved to be valid and reproducible and allowed a semiquantitative
      scoring. Additionally, the amount of blood loss as graded did not influence the
      presented rat adhesion model.

PMID- 8150380
TI  - [Unusual course of scapho-capitate syndrome].
AB  - The scapho-capitate-syndrome has been defined as combined fractures of the
      scaphoid and capitate with rotation of the proximal fragment of the capitate
      through 90 or 180 degrees. Most injuries are due to falls from heights or car
      accidents. Only 26 cases of the scapho-capitate fracture syndrome have been
      reported since 1937. In nearly one third of these cases, there was a delay of
      more than two weeks in diagnosis. We report a case of a young man in whom the
      complex injury was erroneously diagnosed as an isolated fracture of the scaphoid.
      The scaphoid fracture was treated by a screw and healed well. Although the
      patient suffered persistent pain in his wrist, the correct diagnosis was made
      only two years later. During revision operation we found the head of the capitate
      still inverted and with marked signs of avascular necrosis and destruction of the
      lunate cartilage. The avascular fragment was removed and substituted by a graft
      from the iliac crest. The capitate and lunate were fused.

PMID- 8150381
TI  - [Combined arthrosis manifestation of the radial wrist joint].
AB  - In the following study, the basal joint of the thumb and its neighboring joints
      of 100 anatomical specimens were inspected radiologically and macroscopically for
      arthrotic alterations. The comparison of the radiological and macroscopic
      findings showed that early arthrotic joint alterations cannot be diagnosed by
      radiograms. Virtually half of the specimens examined demonstrated arthrotic
      lesions of the basal joint of the thumb, whereas the trapezio-scaphoidal and
      trapezoido-scaphoidal joints were only affected in one-third of the specimens.
      Two-thirds of the cases with manifest arthrosis of the metacarpophalangeal joint
      of the thumb demonstrated additional arthrotic changes in the joints between the
      scaphoid, trapezium, and trapezoideum. No macroscopic evidence of arthrotic
      alterations in the remaining radial carpal bones were observed. The architecture
      of the capsular and ligamentous apparatus as well as the individual variations in
      the scaphoid bone have both been discussed as possible causes of these phenomena,
      as were polyarthrotic or secondary arthrotic processes.

PMID- 8150382
TI  - Distal radius fracture and the distal radioulnar joint--anatomical
      considerations.
AB  - The ulna represents the non-rotating, stable and weightbearing part of the
      forearm around which the radius rotates in pronation and supination. The distal
      radioulnar joint is the distal half of an articulation, the proximal half of
      which is the proximal radioulnar joint. In spite of the distance between the two,
      the distal and proximal radioulnar joints together form a bi-condylar joint, the
      "forearm joint", with the axis of rotation running from the centre of the radial
      head out distally into the interosseous space towards the centre of the ulnar
      head. The end of the radius together with the hand and what is held in the hand
      will rest against the stable, immobile ulnar head, which acts as the keystone of
      the wrist. Mobility and stability of the distal radioulnar joint is accomplished
      by the combined action between fully congruent articulating surfaces and intact
      radioulnar ligaments. Following a distal radius fracture, the semilunar notch of
      the radius will no longer be congruent to the ulnar head due to the displacement
      of the distal fracture fragment of the radius into either dorsal angulation,
      radial angulation, or both. The stabilizing ligaments will tear. Any
      posttraumatic disabling dysfunction of the distal radioulnar joint should
      accordingly be treated by a corrective osteotomy of the radius at the fracture
      site in order to achieve full congruity between the semilunar notch and the ulnar
      head. Resection of the ulnar head deprives the wrist its keystone and should
      therefore be avoided.

PMID- 8150383
TI  - [Bilateral symmetrical absence of the hamulus ossis hamati].
AB  - In a 39-year-old man, bilateral absence of the hook of the hamate was discovered
      by chance. Diagnostic steps and differential diagnoses are presented.

PMID- 8150384
TI  - [Intramedullary nailing of distal mid-hand fractures--technique, instruments,
      case reports].
AB  - Dislocation and instability of distal metacarpal fractures necessitate open
      reduction and stable fixation. Several methods of internal fixation have been
      described, but all of them are technically difficult. Intramedullary pinning from
      proximal to distal, first described by Foucher in 1976, is a dynamically stable
      operation method and easy to perform. New instruments and the newly developed pin
      have been constructed and adapted to the operation method. All is kept as
      technically straightforward as possible. Demonstration of the handling and
      clinical cases are described, and advantages of the procedure emphasized.

PMID- 8150385
TI  - Trigger wrist induced by finger movement. Pathogenesis and differential
      diagnosis.
AB  - Four cases of trigger wrist induced by finger motion are reported. The cause of
      trigger wrist induced by finger motion was a rheumatoid nodule in one case, giant
      cell tumor of the flexor tendon sheath in one case, partial laceration of the
      flexor digitorium superficialis tendon in one case, and lipofibroma in one case.
      Triggering or snapping at the wrist is also induced by motion of the wrist and
      forearm. Reported cases were also analyzed and the clinical entity of the true
      trigger wrist and differential diagnosis were discussed.

PMID- 8150386
TI  - [Dislocation fracture of the base of the 5th metacarpus with hamate involvement
      (dorso-ulnar flake fracture)].
AB  - An uncommon case of a closed dorsal fracture dislocation of the base of the fifth
      metacarpal bone associated with a flake fracture of the hamate is described.
      Under general anaesthesia, the dislocation was reduced by traction and direct
      pressure over the metacarpal base. To maintain the reduction, Kirschner wires
      were inserted percutaneously.

PMID- 8150387
TI  - [Treatment of palmar dislocation and ulnar deviation of the metacarpophalangeal
      joint in chronic rheumatoid arthritis by modified Vainio arthroplasty].
AB  - In rheumatoid arthritis, a number of surgical procedures address the pathology at
      the metacarpophalangeal joint level. Besides synovialectomy, the use of
      endoprothetics is widespread. Particularly during the last years, more importance
      has again been attached to resection arthroplasty technique (e.g. Vainio's
      technique). The authors introduce a modified technique of Vainio's resection
      arthroplasty, permitting an active reposition of the proximal phalanx from its
      previous palmar dislocation and ulnar deviation. First clinical experience
      confirms the efficacy of this modified technique.

PMID- 8150388
TI  - [The Dellon tube in injuries of peripheral nerves].
AB  - Experimental efforts are being undertaken to improve nerve transplantation as a
      method for peripheral nerve repair. Major disadvantages of nerve transplantation
      are the creation of neurologic deficits at the donor site and the limited
      availability of nerve grafts. Mackinnon and Dellon propose the interposition of
      synthetic, biodegradable tubes as a nerve conduit for clinical use. This method
      is described according to its theoretical background and the surgical technique.
      The interposition of synthetic tubes seems possible for short defects in finger
      nerves, but will render unfavourable results in long defects of peripheral mixed
      nerves.

PMID- 8150389
TI  - [Local complications after poisonous snake bite].
AB  - The case of a zoo keeper who was bitten on the left finger by a venomous snake
      (Vipera xanthina) is reported. The administration of antivenom prevented the
      development of systemic poisoning but had no effect on the extent of the local
      complications. A compartment syndrome with a concomitant severe reaction at the
      bite site required fasciotomy of the upper and lower arm. The extensor tendon of
      the involved finger ruptured spontaneously, many weeks after wound healing was
      completed. Therefore, delayed local complications following snake bites may
      occur, even if signs of systemic poisoning are missing.

PMID- 8150390
TI  - [Pulley for strengthening a muscle replacement operation across two joints in
      brachial plexus lesion: description of the surgical technique].
AB  - The reconstruction of lost muscle functions in cases of brachial plexus lesion is
      possible even in those cases where primary nerve reconstruction was not performed
      or unsuccessful. If there are only few motor nerves available, we prefer free
      latissimus dorsi transplantation or pedicled latissimus dorsi transposition for
      replacement of biceps and finger flexors. The combination of elbow flexion and
      finger flexion becomes possible when the transposed motor is passed around a
      suitable pulley in the elbow region like the flexor carpi ulnaris or carpi
      radialis.

PMID- 8150391
TI  - [Exercise-stable arthrodesis of the area of the wrist joint using bone staplers].
AB  - In 32 of 40 cases of limited wrist fusion using bone staples, immobilization
      after wound healing was unnecessary. In 27 of 30 controlled cases, we found
      adequate bone healing. Two cases of non-union and one case of partial healing
      were due to the operative technique, not to the method of fixation.

PMID- 8150392
TI  - Caseicin, a bacteriocin from Lactobacillus casei.
AB  - The intracellular bacteriocin caseicin 80 was purified from cell extracts of
      Lactobacillus casei strain B80. It is a thermolabile protein with an apparent
      molar mass of 42 kDa. As no plasmids were observed in the bacteriocinogenic
      strain it is assumed that caseicin is encoded by the bacterial chromosome. Using
      14C-labelled precursors it was found that biosynthesis of DNA and proteins was
      influenced by caseicin but this inhibition is probably not the primary effect.
      The incorporation of fructose but not of glucose into cellular material was
      inhibited by caseicin.

PMID- 8150393
TI  - Influences of chemical fertilizers (in vitro) on aflatoxin and citrinin synthesis
      by two strains of aspergilli.
AB  - The selective effect of various levels of phosphate and nitrate (as fertilizers)
      on biosynthesis of aflatoxin by Aspergillus parasiticus var. globosus, and
      citrinin by A. terreus var. aureus was studied in defined culture medium.
      Phosphate at 35-175 mmol per 50 mL decreased aflatoxin production, but increased
      citrinin synthesis. Nitrate at 73-365 mmol per 50 mL stimulated the synthesis of
      aflatoxin but depressed that of citrinin. A rise in the levels of nitrate and
      phosphate led to a decrease in aflatoxin production, an increase in citrinin
      production and an accumulation of mycelial phosphate and nitrate contents.

PMID- 8150394
TI  - Pectin transeliminase complex from Aspergillus flavus.
AB  - Aspergillus flavus grown in a liquid medium containing pectin as the sole carbon
      source produced extracellular enzymes which degraded the 1,4-alpha-D-glycosidic
      bonds of pectin. The products of degradation were characteristic of substances
      produced by transeliminase. Synthesis of this enzyme was repressed by the
      addition of sucrose, glucose, fructose and maltose. The crude enzyme was
      partially purified by a combination of ultrafiltration and ammonium sulfate
      precipitation. The partially purified enzyme was separated by molecular exclusion
      chromatography into three components A, B and C, with molar masses ranging from
      13.2 to 64 kDa. Only fraction B exhibited enzymic activity and further
      fractionated by ion-exchange chromatography into four components I-IV. Among
      these components, only fractions I and II possessed transeliminase activity. Both
      fractions had an optimum activity at pH 8.5 and 35 degrees C, and were stimulated
      by Ca2+, Mg2+, Na+ and K+ but inhibited by EDTA and DNP. The apparent Km for the
      degradation of pectin by fractions I and II were 6.2 and 8.0 g/L, respectively.

PMID- 8150395
TI  - Biochemical, morphological and cytochemical studies of enhanced autolysis of
      Saccharomyces cerevisiae. 1. Biochemical studies.
AB  - Biochemical aspects of induced autolysis of Saccharomyces cerevisiae were
      observed in the presence of various physical and chemical enhancers of autolysis
      (increased temperature, changes of pH, NaCl, ethanol, fresh autolyzate). Direct
      assays of proteinases, nucleases, glucanases and acid phosphatases in homogenized
      autolyzed cells were performed. In addition, the degradation products of
      proteins, nucleic acids, polysaccharides and phosphate from phosphorylated
      compounds were determined in the supernatant of autolyzate after centrifugation.
      These results suggested that the inducers affected transport processes and that
      they had mostly negative effects on the activities of the above-mentioned
      enzymes.

PMID- 8150396
TI  - Biochemical, morphological and cytochemical studies of enhanced autolysis of
      Saccharomyces cerevisiae. 2. Morphological and cytochemical studies.
AB  - Morphological and cytochemical observation of Saccharomyces cerevisiae undergoing
      of induced autolysis were done in response to various chemical inducers of
      autolysis (NaCl, ethanol, fresh autolyzate). Changes in the inner structure of
      yeast cells were monitored by transmission electron microscopy and the surface of
      the cell wall was observed by scanning electron microscopy during autolysis.
      Cytochemical characterization of autolyzed cells was performed using four
      synthetic substrates for determination of proteinase activities but only
      carboxypeptidase Y could be detected in the vacuolar membranes. The morphological
      studies supported the data obtained from biochemical studies and confirmed that
      optimized conditions of autolysis have a significant effect on the structural
      changes of autolyzed yeast.

PMID- 8150397
TI  - Inhibitory action of palmitic acid on the growth of Saccharomyces cerevisiae.
AB  - High concentrations of long-chain fatty acids have been found to be harmful to
      mammalian cells and prokaryotic organisms. This effect was investigated in
      Saccharomyces cerevisiae. Addition of 3 mmol/L palmitate to a yeast extract
      peptone medium caused a significant inhibition of cell growth during the first 2
      d of incubation, followed by renewed growth and palmitate utilization. Inhibition
      was also observed with palmitate concentrations down to 0.1 mmol/L. As inferred
      from catalase activity determinations, this effect was found to correlate with
      the absence of peroxisome proliferation. Finally, no inhibition was observed in
      exponential-phase cultures or in the presence of 0.1 g/L glucose, this suggesting
      that the physiological state of the cell may determine whether its growth will be
      inhibited by fatty acids.

PMID- 8150398
TI  - Dermatophytes and other associated fungi isolated from ringworm lesions of
      camels.
AB  - Among 75 camels showing skin lesions, 48% were positive for fungal infection. The
      younger individuals were more susceptible to this infection. Sixteen species
      belonging to nine genera of keratinophilic and cycloheximide-resistant fungi were
      recovered from diseased camels. Trichophyton, Microsporum and Chrysosporium were
      the most common genera. T. verrucosum appeared to be the main cause of ringworm
      in small camels while T. mentagrophytes infected older ones. Camel skin presents
      a suitable habitat for the growth of some dermatophytes and other potentially
      pathogenic fungi.

PMID- 8150399
TI  - Factors affecting the susceptibility of sensitive yeast cells to killer toxin K1.
AB  - Optimum conditions for action of the killer toxin K1 on sensitive strain S.
      cerevisiae S6 were established. Maximum killing was reached in a very narrow pH
      range of 4.5-4.6. Maximum susceptibility to toxin was displayed by highly
      energized fresh cells from the early exponential phase in the presence of an
      external energy source (at least 200 mmol/L glucose). Further, maintenance of
      maximum membrane potential was necessary for killer action, as documented by
      decreasing toxin activity in the presence of increasing concentrations of KCl.
      The killing was strongly stimulated in the presence of millimolar concentrations
      of Ca2+ and Mg2+.

PMID- 8150400
TI  - [Management of AIDS patients in general practice. Confidentiality--alternative
      therapy].

PMID- 8150401
TI  - [Therapy of diabetes mellitus].

PMID- 8150402
TI  - [Fear, violence and depression--does too little serotonin make the mind ill?].

PMID- 8150403
TI  - [Risks and complications of contact lens use].
AB  - Hard and soft contact lenses are not always well tolerated--a certain percentage
      of lens wearers develop eye complications, which may be either mechanical toxic,
      metabolic, or allergic in nature and are caused by sensitization of the anterior
      part of the eye by cleaning/disinfecting media or the material of the lens.
      Inadequate cleaning or disinfection of the lens can also lead to eye injury, as
      can leaving the lens in the eye for too long. Only thorough patient instruction
      on the handling and care of the lenses, coupled with regular visits to the
      ophthalmologist can avoid the development of complications in contact lens
      wearers.

PMID- 8150404
TI  - [Non-tropical pyomyositis].
AB  - This is a report on a 51-year-old man with all the symptoms of a non-tropical
      pyomyositis, namely a prodromal stage with lassitude, associated with a high
      fever and diffuse joint and muscle pain followed by the gradual development of a
      full-blown invasive stage. In the suppurative stage, the extensive pus is caused
      by staphylococcus aureus located in the extensor muscle of the right thigh.

PMID- 8150405
TI  - [Preventive treatment before foreign travel. 2: Prevention of malaria].

PMID- 8150406
TI  - [Psychopharmacology since 1952].
AB  - When chlorpromazine was introduced into psychiatric therapy in 1952 and thus the
      modern psychopharmacological era was started, the situation in psychiatry was
      deplorable. The psychiatric hospitals were overcrowded and obsolete,
      complementary institutions were widely missing. In Germany, even after
      introducing the neuroleptic era and the beginning of the thymoleptic epoch in
      1957, no decisive improvement took place at first. As late as in the 70s
      successes of psychiatric reform efforts in the sense of humanization became
      visible, along with modern psychopharmacotherapy making an important contribution
      to these improvements. With the social attitude towards the mentally ill
      changing, this contribution became effective. In 1954 the antipsychotic efficacy
      of Rauwolfia alkaloids was described; in 1958 the butyrophenones, especially
      haloperidol, were introduced. In 1957 the antidepressive efficacy of imipramine
      was discovered, in the same year the psychiatric importance of monoaminoxidase
      inhibitors was defined. In 1949 Cade published his findings on the antimanic
      effect of lithium salts. As tranquilizers meprobamate (1955) and chlordiazepoxide
      (1960) were made available. In 1966 clozapine was introduced. Objections to
      psychopharmacotherapy, which were not always objective, were often raised. The
      biochemical research in cooperation with psychopharmacology has made progress,
      yet the target of clarification of the pathophysiology of the main psychoses has
      not been reached as yet. At present there is considerable resistance towards a
      further expansion of psychopharmacology, research being hampered by legal
      reglementation and bureaucracy. This development must be faced.
      Psychopharmacotherapy is not yet sufficiently effective and safe; it must be
      improved.

PMID- 8150407
TI  - [Inadequate utilization of somato-medical services by psychogenically ill
      patients].
AB  - Within the Mannheim Cohort Project on the epidemiology of psychogenic disorders
      240 probands of a high risk sample (suffering from medium psychogenic impairment)
      were randomly selected from the general population and investigated with regard
      to their realized utilization of the medical and/or psychotherapeutic services of
      the health care system. On the basis of clinical criteria the probands were
      classified as case (n = 78) of psychogenic disorder or non-case (n = 162).
      Increased psychogenic impairment caused by psychoneurotic, character neurotic, or
      psychosomatic-functional disorders was primarily combined with an intensified
      utilization of the somatically oriented medical services. Only 2.5% of the cases
      indicated that the reason for their most recent visit to a physician was
      psychotherapeutic treatment. In view of the high percentage of psychogenic
      impaired patients in private practices and general hospitals this seems to be a
      particularly discrepant finding. In spite of the psychogenic nature of their
      complaints the cases were confronted with somatically oriented therapy offers
      like the non-cases. An increased psychogenic impairment did not lead to a
      qualitative alteration of the utilization of medical and/or psychotherapeutic
      services. Facing the fact that the utilization of somatically oriented medical
      services by psychogenic ill patients is still widespread but inadequate this
      finding is interpreted as indication for an essential demand of further studies
      on the determinants of psychotherapy acceptance.

PMID- 8150408
TI  - [Unilateral caudal cranial nerve paralysis in extracranial carotid dissection].
AB  - Focal cerebral ischemic symptoms, Horner's syndrome and mostly ipsilateral
      headache are the characteristic clinical triad of extracranial carotid artery
      dissection. Lower cranial nerve palsies seem to be uncommon and rare. By means of
      two cases with identical clinical symptoms and of a literature review we make
      clear, that ipsilateral lower cranial nerve palsies, especially a hypoglossal
      nerve palsy, are not uncommon. Without focal cerebral ischemic symptoms they can
      be the only sign of extracranial carotid artery dissection. Computed tomography
      of the skull base with regard to the high cervical internal carotid artery is as
      an usually quickly available examination an alternative to magnetic resonance
      imaging.

PMID- 8150409
TI  - [The illness concept of children--review of the literature].
AB  - In this literature review a group of studies concerning illness concepts of
      children are discussed. Most of these studies are based on one of the three
      theory models of cognitive development as the main factor of development of
      illness concepts, the attributional theory (health locus of control) or the
      health belief model based on health seeking behaviour. The results yielded by
      these theories are comparable to a limited extent only. The development of
      children's illness concepts seems to be mainly influenced by age, developmental
      stage, self-consciousness and family ties.

PMID- 8150410
TI  - [Myocardial vitality: clinical correlates and diagnostic concepts].
AB  - Modern therapeutic options in ischemic coronary disease such as thrombolysis,
      coronary angioplasty, new emerging strategies in treating heart failure and
      secondary prevention have resulted in decreasing cardiac mortality over the last
      ten years. In the era of interventional cardiology a new focus of clinical
      interest is the process of transition from loss of contractile function to
      definitive necrosis of severely ischemic myocardium. The decision for bypass
      surgery or angioplasty in patients with compromised contractile function should
      be based on evidence of viable myocardium with some or full potential for
      functional recovery; otherwise prognostic benefit may be questionable or dubious.
      The clinical substrate of non-contractile, but viable myocardial tissue may be
      present in patient presenting with both stable and unstable angina, in cases of
      acute or chronic myocardial infarction and in the setting of congestive heart
      failure resulting from ischemic cardiomyopathy. Various diagnostic methods are
      theoretically useful to assess residual myocardial viability both in hibernating
      myocardium (contractile down-regulation) and post-ischemic stunned (reperfused)
      myocardial tissue. Myocardial viability is confirmed both in presence of systolic
      wall motion or systolic wall thickening as evidenced from (contrast or
      radionuclide) left ventricular angiograms or echograms. Moreover, myocardial
      tissue perfusion by thallium-201 or other radioactive perfusion agents as
      documented by uptake of tracer is considered clear evidence of viability;
      however, lack of uptake of perfusion agents may not always exclude viable
      myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150411
TI  - Potential and limitations of Tc-99m sestamibi scintigraphy for the diagnosis of
      myocardial viability.
AB  - Sestamibi is a Tc labeled radiotracer particularly suitable for myocardial
      perfusion studies, providing similar information as thallium scintigraphy for the
      diagnosis of coronary artery disease. In comparison with thallium, sestamibi has
      the advantage of improved imaging properties due to its higher gamma emission.
      This is particularly relevant when SPECT imaging is considered. The myocardial
      uptake of sestamibi is partially passively, related to the myocardial flow, and
      is also related to the metabolic cellular activity, as it is proportional to the
      electrochemical gradient generated at cell membrane level. While the role for
      sestamibi in diagnosing coronary artery disease is well accepted, it is still
      controversial for the assessment of myocardial viability. Clinical studies
      reported by others and results from our own institution will be described both in
      the setting of a recent myocardial infarction (myocardial stunning) and of
      longstanding left ventricular dysfunction (hibernating myocardium). The results
      concordantly suggest that sestamibi underestimates myocardial viability, compared
      to the accepted standards of thallium (rest-redistribution or stress-reinjection
      protocols), 18-F FDG PET and also in the prediction of left ventricular
      functional recovery after revascularisation. However, the data available at
      present are very limited, particularly after revascularisation. Furthermore,
      according to new promising results, the role of sestamibi in the setting of
      myocardial viability has potential for improvement, if the injection at rest will
      be performed during nitrates. It is also foreseen that the combined use of
      sestamibi perfusion/wall motion scan (first pass and/or gated perfusion studies)
      and the development of new softwares for attenuation correction might improve the
      results in the setting of myocardial viability.

PMID- 8150412
TI  - Persistent twenty-four hour SPECT thallium-201 defects, plasma thallium-201
      concentrations and PET metabolic viability.
AB  - Previous studies have shown that defects on four hour thallium-201 redistribution
      images often exhibit late reversibility, suggesting that the thallium-201
      scintigraphic assessment of myocardial viability might be influenced by delayed
      redistribution imaging. To assess tissue metabolic activity in segments with late
      thallium-201 defects, positron emission tomography (PET) with 13NH3 and 18FDG was
      performed in 26 coronary artery disease patients with left ventricular
      dysfunction undergoing twenty-four hour SPECT thallium-201 scintigraphy. In 13
      patients, plasma thallium-201 levels were obtained at the time of SPECT study and
      integrated tracer concentrations were determined one, two, four and twenty-four
      hours following injection. On circumferential profile image analysis of the PET
      images, ischemia was defined by preserved glucose metabolism in hypoperfused
      myocardium while infarction was identified by concordant reductions in both
      perfusion and glucose metabolism. Nineteen patients had stress-redistribution
      SPECT studies and seven had rest-redistribution SPECT studies. Using a semi
      quantitative scoring system, four experienced observers visually identified 100
      fixed, 17 partially reversible and twelve completely reversible segmental SPECT
      thallium-201 defects. On PET, metabolic activity was identified in 51 (51%) fixed
      defects (21 PET ischemia, 30 PET normal) and nine (53%) partially reversible
      defects (five PET ischemia, four PET normal). Of the twelve completely reversible
      thallium-201 defects, six (50%) were normal on PET, five (42%) had PET ischemia
      and one (8%) had PET infarction. The relative number of fixed thallium-201
      defects with metabolic activity on PET did not depend on whether a stress or rest
      thallium-201 study was performed, or on whether the plasma thallium-201 integral
      concentration was high or low relative to mean values at any time point. Despite
      delayed redistribution imaging, PET imaging identifies glucose metabolic
      activity, and therefore residual tissue viability, in the majority of fixed
      twenty-four hour thallium-201 defects.

PMID- 8150413
TI  - Assessment of tissue viability with fluorine-18-fluoro-2-deoxyglucose (FDG) and
      carbon-11-acetate PET imaging.
AB  - Positron emission tomography allows noninvasive assessment of myocardial
      metabolic processes and perfusion. Myocardial F-18-2 deoxyglucose (FDG) uptake as
      assessed by PET imaging has been established as a metabolic tracer indicating
      myocardial viability, whereas N-13 ammonia uptake reflects myocardial perfusion.
      Furthermore, it has been shown that the clearance of C-11-acetate in normal and
      ischemic myocardium correlates closely with overall myocardial oxygen consumption
      (MVO2). Therefore, C-11-acetate PET imaging has been proposed as a tracer for
      myocardial viability. In contrast with myocardial FDG uptake, the clearance of C
      11-acetate is independent from overall substrate utilization. In the present time
      the highly expensive PET studies should only be performed in patients with
      chronic advanced coronary artery disease resulting in severely impaired left
      ventricular function. Moreover, coronary anatomy has to be suitable for
      revascularization and there has to be an absence of reversible perfusion
      abnormalities on Tl-201-chloride reinjection SPECT scans. This review focuses on
      clinical studies employing C-11-acetate and FDG PET imaging in patients with
      advanced chronic coronary artery disease, acute myocardial infarction and after
      heart transplantation. Clinical applications of FDG and C-11-acetate PET imaging
      and prognosis of PET flow-metabolic imaging regarding recovery of myocardial
      function and clinical outcome after revascularization and thrombolytic therapy
      are summarized. Furthermore, PET results are compared to SPECT imaging with Tl
      201 and Tc-99m-MIBI.

PMID- 8150414
TI  - [Magnetic resonance tomography imaging techniques for diagnosing myocardial
      vitality].
AB  - In contrast to the established nuclear imaging techniques magnetic resonance
      imaging (MRI) is only in the early phase of its application to detect viable
      myocardium after myocardial infarction. Although MRI techniques have only
      recently been employed to assess residual myocardial viability three approaches
      have been described to achieve this purpose: First, the use of signal intensity
      changes on spin-echo images with and without the application of contrast media to
      define irreversible injury to the myocardium in acute and subacute infarcts;
      second, measurement of metabolite concentrations within the infarct area using
      magnetic resonance spectroscopy, and third quantitation of myocardial thickness
      and systolic wall thickening in chronic infarcts with and without positive
      inotropic stimulation. When applying magnetic resonance techniques to detect
      viable myocardium by imaging techniques, it is useful to distinguish between
      acute infarcts and chronic infarcts that are more than 16 weeks old. After the
      time, practically all infarcts have healed and the necrotic myocardium has been
      transformed into scar tissue. MRI seems ideally suited to detect and characterize
      chronic myocardial scar and distinguish it from viable but hibernating myocardium
      because it clearly depicts the regional wall thinning which is a typical feature
      of transmural infarcts (Figure 1). In contrast, more recent infarcts, even if
      they are transmural and fail to show any contraction during systole, may not yet
      exhibit myocardial thinning. Therefore, simply depicting the acutely injured
      myocardium by MRI is not sufficient to differentiate between necrotic and
      stunned, but viable myocardium. On the other hand, an increase in signal
      intensity of acutely infarcted myocardium, which appears on T2 weighted spin-echo
      MR images only a few hours after occlusion of a coronary artery, can be used to
      determine the extent of irreversible myocardial damage (Figure 2). It is not
      clear, however, whether this area of increased myocardial signal intensity that
      is seen within the first week after the event only represents necrotic myocardium
      or incorporates some edematous viable myocardium in the infarct border zone.
      After three weeks, true infarct size may be more closely approximated by the area
      of increased signal intensity because the edema surrounding the infarct has
      presumably regressed and signal abnormalities are restricted to the
      pathologically determined infarct area. More recently, new pulse sequences and
      high field magnets permit separate observation of the endocardial and epicardial
      portion of the left ventricular wall. This may further improve the detection of
      residual viable cells which are preferentially located near the
      epicardium.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8150415
TI  - [Case report. Thrombolytic therapy 17 hours after acute myocardial infarct:
      assessing myocardial viability with 201 thallium imaging].

PMID- 8150416
TI  - [Thallium scintigraphy for determining myocardial vitality. Evaluation of the
      "stunned and hibernating myocardium"].
AB  - Myocardial uptake of 201thallium is not only a function of regional myocardial
      blood flow, but also reflects cellular uptake by intact cell membranes and thus
      can not be merely regarded a signal of perfusion but also of structural cell
      integrity. Especially in the setting of severely depressed left ventricular
      function evidence of viable but dysfunctional myocardium has impact on recovery
      potential and prognosis after myocardial revascularization. Hibernating
      myocardium, a reversible chronically ischemic state of reduced aerobic metabolism
      and depressed contractile function, may be identified after injection of
      201thallium at rest and rest-redistribution SPECT imaging. Since 201thallium
      uptake in initial defect areas may occur as a function of time allowed for
      redistribution, even partial late uptake may be considered a reliable signal for
      viable, but hibernating tissue, 75% of which demonstrating contractile recovery
      after revascularization. Uptake of 201thallium at rest or with redistribution,
      thus, is indicative of myocardial viability irrespective of function. Conversely,
      lack of 201thallium uptake after stress and redistribution does not always
      indicate necrosis, since 45 to 83% of myocardium with no uptake may improve
      function after revascularization. These defects, however, often resolve with
      reinjection of 201thallium and subsequent imaging at rest. This observation led
      to a triphasic imaging protocol including conventional rest-redistribution
      imaging and a third set of images after reinjection of 1 mCi 201thallium at rest.
      This concept ensures uptake of 201thallium in 31 to 49% of presumably persistent
      defects and increases sensitivity for detection of viable tissue. In 80 to 87% of
      areas with reinjection 201thallium uptake function improved after
      revascularization compared to 0 to 8% of segments with no uptake at all.
      Redistribution imaging should not be omitted for logistical reasons, since
      important information not only on ischemia but also on viability may be lost.
      Useful imaging protocols for detection of both ischemia and viability comprise
      either a sequence of stress, redistribution and reinjection imaging or a series
      of stress, reinjection and 24 hour redistribution images; both protocols have
      similar sensitivity for detection of tissue viability. In the setting of stunned
      myocardium mainly after thrombolytic therapy the assessment of residual viability
      may be important for both additional therapeutic and prognostic reasons.
      201Thallium uptake preferentially using a re-redistribution protocol may help to
      differentiate viable from non-viable myocardium; however 201 thallium imaging
      should be performed after the hyperemic phase following successful thrombolysis
      (> or = 24 to 48 hours after thrombolysis).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8150417
TI  - Inactivation of Cu,Zn-superoxide dismutase by in vitro glycosylation and in
      erythrocytes of diabetic patients.
AB  - Purified bovine Cu,Zn-superoxide dismutase was nonenzymatically glycosylated in
      vitro at a rate proportional to incubation time (2 to 120 hrs) and glucose
      concentration (10 to 100 mM). Inverse correlation between glycosylation and the
      enzyme activity showed that increased glycosylation was accompanied with
      inactivation of the enzyme. Specific activities of glycosylated and non
      glycosylated enzymes incubated with 100 mM glucose for 120 hrs were 1150 and 2860
      units/mg protein, respectively. This indicates that nonenzymatic glycosylation
      declined the enzyme activity approximately to 40%. All these results were
      consistent with the in vivo studies that Cu,Zn-superoxide dismutase activity in
      erythrocytes of non-insulin dependent diabetic patients was inversely correlated
      with their plasma glucose. Inactivation of Cu,Zn-superoxide dismutase
      demonstrated by both in vitro and in vivo studies may be important for the
      development of diabetic complications, because the enzyme has a crucial role in
      protecting the body against the damaging effects of the superoxide radicals.

PMID- 8150418
TI  - Effects of nerve growth factor and dexamethasone on Na+,K(+)-ATPase of cultured
      PC12h cells.
AB  - When PC12h cells were cultured for 4 days in the presence of 50 ng/ml of nerve
      growth factor (NGF), they showed elongated dendrites and specifically increased
      Na+,K(+)-ATPase activity. Either singly or in combination with NGF, dexamethasone
      also increased the specific activity of this enzyme. Western blot analysis using
      anti-alpha 1 and anti-alpha 2 antisera showed that PC12h cells, either before or
      after hormone treatment, contained the alpha 1 isoform but not the alpha 2 one.
      We conclude, therefore, that NGF induces Na+,K(+)-ATPase concomitantly with
      neuronal differentiation in PC12h cells but that the growth factor does not
      induce formation of the myelin sheath, which normally expresses the alpha 2
      isoform of Na+,K(+)-ATPase.

PMID- 8150419
TI  - Androgenic modulation of lipid metabolism at subcellular sites in cholestatic
      rats.
AB  - The present studies examine the modulation of lipid metabolism at subcellular
      sites in the liver of control and cholestatic rats by a male sex hormone.
      Subcutaneous injection of testosterone enanthate (5 mg/kg body weight), increased
      triacylglycerol lipase (TG-lipase) and neutral cholesterol ester hydrolase (CE
      hydrolase) activity in endosomes of normal rats. During induced cholestasis, TG
      lipase and CE-hydrolase activity in endosomal fractions were decreased compared
      to those in endosomes of age-matched sham-operated female controls. Following
      testosterone administration to cholestatic rats, endosomal lipolytic enzyme
      activity increased to approximate the levels of normal controls. These
      observations may provide insight into the alterations in lipid metabolism which
      accompany cholestatic liver disease.

PMID- 8150420
TI  - Reduction of red cell glucose transporter intrinsic activity in diabetes running.
AB  - The function of the red blood cell glucose transporter was compared in samples
      from subjects with and without diabetes. Activity of the glucose transporting
      protein (GLUT-1) was measured by determining the first order rate constant for
      uptake of sorbose, a sugar transported by GLUT-1. Red cells were isolated from 13
      patients with diabetes and 9 patients without diabetes and were washed free of
      intracellular glucose. The uptake rate constant was calculated from measurements
      of sorbose uptake at 0, 1, 2, 5 and 90 minutes at 37 degrees C. The rate constant
      was significantly decreased in cells isolated from patients with diabetes (0.242
      vs 0.303 min-1 in non-diabetic subjects, p < 0.005). The number of GLUT-1 present
      per mg of membrane protein and clinical parameters such as weight, age, serum
      cholesterol and urea nitrogen were not significantly different between the
      groups. The rate constant per pmol of GLUT-1 was significantly decreased in the
      diabetic subjects. The relationship between diabetes control and the rate
      constant was not linear and there was no relationship between the calculated
      intrinsic activity and the HA1c. Because red cell GLUT-1 are not translocated and
      red cells do not synthesize new proteins, these data suggest that the intrinsic
      function of the glucose transporter from red cells of patients with diabetes is
      diminished. This may be due to alterations in the transporter or its membrane
      environment.

PMID- 8150421
TI  - Reduction of erythrocyte (Na(+)-K+)ATPase activity in type 2 (non-insulin
      dependent) diabetic patients with microalbuminuria.
AB  - In order to elucidate the causal relationship between (Na(+)-K+)ATPase and
      diabetic nephropathy, we studied the erythrocyte (Na(+)-K+)ATPase activity in
      Type 2 diabetic patients, 20 with microalbuminuria and 27 without
      microalbuminuria and in 16 control subjects. (Na(+)-K+)ATPase activities in
      microalbuminuric patients (0.273 +/- 0.012 mumol Pi/mg protein/h, mean +/- SE)
      were significantly reduced compared with those without microalbuminuric patients
      (0.308 +/- 0.011 mumol Pi/mg protein/h, p < 0.05) and control subjects (0.330 +/-
      0.011 mumol Pi/mg protein/h, p < 0.01). Microalbuminuric patients had higher
      systolic blood pressure (133 +/- 3 vs 124 +/- 3 mmHg, p < 0.05) and greater
      frequency of parental hypertension (50% vs 19%, p < 0.05) than those without
      microalbuminuria. (Na(+)-K+)ATPase activities in diabetic patients with
      hypertension were significantly reduced compared with those in diabetic patients
      without hypertension. Moreover, (Na(+)-K+)ATPase activities in diabetic patients
      with parental hypertension were significantly reduced compared with those in
      patients without parental hypertension. There was no difference in erythrocyte
      Na+ content between with and without microalbuminuria or hypertension or parental
      hypertension in diabetic patients. Erythrocyte Na+ content was significantly
      negatively correlated with (Na(+)-K+)ATPase activity in control subjects (r = 
      0.619, p < 0.05), but not in diabetic patients (r = -0.194). Plasma digitalis
      like substances showed no correlation with (Na(+)-K+)ATPase activities in
      diabetic patients with microalbuminuria or hypertension or parental hypertension.
      We concluded that the reduction of erythrocyte (Na(+)-K+)ATPase activity may be
      related to a familial predisposition to arterial hypertension and may partly be
      responsible for the development of diabetic nephropathy in Type 2 diabetic
      patients.

PMID- 8150422
TI  - Biochemical effects of a calcium supplement in postmenopausal women with primary
      hyperparathyroidism.
AB  - Oral calcium loading is known to decrease parathyroid hormone levels in primary
      hyperparathyroidism. We have examined the effects of a calcium supplement on bone
      resorption in postmenopausal primary hyperparathyroidism. Fasting blood and urine
      samples were obtained in 12 postmenopausal women (median age 64 yr) with primary
      hyperparathyroidism associated with mild hypercalcemia (plasma calcium < 3.00
      mmol/l). Further samples were obtained 12 hours after a 1 g calcium supplement
      given at 2100 h. After calcium administration there were rises in plasma ionized
      calcium (p < 0.02), plasma phosphate (p < 0.05) and the renal tubular maximum
      reabsorption capacity for phosphate (p < 0.01) and falls in parathyroid hormone
      (p < 0.05) and the renal tubular maximum reabsorption capacity for calcium (p <
      0.05). The urinary calcium/creatinine increased (p < 0.01) and the urinary
      hydroxyproline/creatinine (p < 0.02) fell. These results indicate that calcium
      loading inhibits bone resorption in postmenopausal women with mild primary
      hyperparathyroidism.

PMID- 8150423
TI  - Enzyme-linked immunosorbent assay (ELISA) method for screening of non-classical
      steroid 21-hydroxylase deficiency.
AB  - Morning salivary 17-hydroxyprogesterone (17-OHP) determination is a useful method
      to diagnose non-classical 21-hydroxylase deficiency (NC 21-OHD). In ethnic groups
      with high frequency of NC 21-OHD, mass screening is thought to be necessary. A
      pilot screening test for NC 21-OHD was performed by measuring morning salivary 17
      OHP by enzyme-linked immunosorbent assay (ELISA). Two individuals were found NC
      21-OHD from 230 subjects. Results of this ELISA were well correlated with those
      of established radioimmunoassay. ELISA can be performed in any laboratory because
      of non-radioactivity and the procedure is very easy by the use of a microplate.
      This ELISA is suitable for large scale population studies. We conclude that
      morning salivary 17-OHP determination by ELISA is a useful method for NC 21-OHD
      screening test.

PMID- 8150424
TI  - Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral
      density in eumenorrhoeic women with androgen excess.
AB  - Increased bone mineral density (BMD) has been reported in young women with
      androgen excess. To determine whether antiandrogen treatment in young women with
      androgen excess reduces BMD in these patients, the authors measured BMD before
      and a year after the beginning of antiandrogen therapy with spironolactone and
      linestrenol in 17 consecutive androgenized patients (median age 22 years). After
      a year's treatment BMD declined in 15 out of 17 patients, the mean decrease-
      0.032 g/cm2 (95% CI of the difference 0.016-0.048)--being highly significant (p <
      0.001). Androstenedione decrease was the only hormonal variable significantly
      correlating with BMD decrease (r = 0.5; p = 0.037) according to simple linear
      regression. A decrease of BMD might become a key factor in deciding about the
      duration of antiandrogen treatment with spironolactone in functional
      hyperandrogenemia.

PMID- 8150425
TI  - Lack of effects of glucose on IAPP biosynthesis in mouse beta TC3 cells.

PMID- 8150426
TI  - Production of thyroid stimulation blocking antibody without TSH receptor binding
      activity in rabbits with experimental autoimmune thyroiditis.
AB  - When rabbits were immunized with porcine thyroid plasma membrane, some cases of
      produced antibodies showed the blocking activity for TSH stimulated cAMP
      production in cultured porcine thyroid cells in spite of negative TSH binding
      inhibitory immunoglobulin (TBII) activity. The inhibitory effect of these thyroid
      stimulation blocking antibodies (TSBAbs) on cAMP increase by forskolin and GTP
      gamma S in porcine thyroid cells was observed in 1 and 3 rabbits, respectively.
      When the blocking activity of these antibodies for stimulated cAMP production by
      forskolin, GTP gamma S and NaF was examined in the isolated porcine thyroid
      membrane, no blocking activity for these 3 stimulators except in 1 case was
      found. The blocking activity of these antibodies could be absorbed significantly
      by incubation with porcine thyroid plasma membrane as antigen. The blocking
      activity was not observed in rabbits immunized with porcine thyroglobulin. The
      present experiment demonstrated that the produced antibody in rabbits against
      porcine thyroid membrane had the blocking activity for TSH stimulation to thyroid
      cells without affecting TSH binding to its receptor. These facts suggest that
      this type of blocking antibody may be produced against any antigen of thyroid
      membrane origin except the TSH receptor.

PMID- 8150427
TI  - Lipolysis and glycerokinase activity in brown adipose tissue of rat fed a high
      protein, carbohydrate-free diet.

PMID- 8150428
TI  - Effects of oestradiol-17 beta on small intestine iron absorption and iron uptake
      into blood and liver.

PMID- 8150429
TI  - In vitro effects of various albumins on Leydig cell testosterone production in
      immature rat.

PMID- 8150430
TI  - [Study on antibacterial proteins from rabbit bladder mucosa].
AB  - Acid-soluble extract of rabbit bladder mucosa was obtained by washing out the
      bladder of normal female New Zealand rabbit with 1% acetic acid in the presence
      of proteinase inhibitors. Acid urea polyacrylamide electrophoresis (AU-PAGE)
      analysis indicated that the extract had more than 10 main protein bands. The
      currently-known antibiotic peptides, e. g. lysozyme and defensin-like molecules
      were not found in this material. When tested for antibacterial activity by using
      ultrasensitive radial diffusion assay, the acid-soluble extract effectively
      killed E. coli ML-35P. The gel overlay assay showed that the anti-bacterial
      activity of the acid-soluble extract was relevant to two protein bands referred
      to as rabbit bladder protein 1 (Rab BP-1) and rabbit bladder protein 2 (Rab BP
      2). The Rab BP-1 and Rab BP-2 accounted for 2.5% and 1.2% of the total acid
      soluble extract proteins, respectively. These results suggest that the long
      recognized ability of the normal rabbit bladder wall to kill adherent E. coli may
      result from the presence of endogenous antibacterial proteins associated with its
      mucosa.

PMID- 8150431
TI  - [PCR amplification of nerve growth factor (beta-NGF) gene in human brain].
AB  - Nerve growth factor, an important nutrition factor for neuronal survival, growth,
      development and maintenance of neuronal functions, consists of three kinds of
      subunit (alpha 2, beta and gamma 2), but only the subunit beta-NGF has the
      biological activity. beta-NGF coding sequence is located in a single exon of NGF
      gene. In our study, a pair of specific primers (29 mers) has been designed and
      synthesized with ABI 318 A DNA synthesizer. The upstream primer includes an
      initiation codon and the 1st to 20th base of the exon. The downstream primer
      includes the complementary sequence of 334 to 354 base of the exon and a stop
      codon. The full-length DNA fragment of beta-NGF gene has been successfully
      obtained from human brain cDNA library in lambda ZAPII/EcoRI and human brain
      genomic DNA respectively by using polymerase chain reaction. The reaction program
      consists of denaturing at 93 degrees C for 1 min, annealing at 55 degrees C for 1
      min, and extending at 72 degrees C for 2 min. Both amplified products of 350 bp
      in length coincide with the exon coding sequence and are enough for the analysis
      of restriction mapping, DNA sequencing and construction of expression vector.

PMID- 8150432
TI  - [Study of clearance and distribution of 125I-labeled apolipoprotein CIII in
      mice].
AB  - Using 125I-labeled human apoCIII, the clearance and distribution of 125I-apoCIII
      were investigated. Human apoCIII was purified from plasma VLDL. 125I-apoCIII was
      prepared by chloramine T method, The fraction clearance rate (FCR) value of 125I
      apoCIII in mice plasma was 0.19/h with a plasma half life of 3 h. The
      radioactivity in different organs after the venous injection of 125I-apoCIII
      exhibited that the liver contained radioactivity 3-10 times as much as the
      reactivity in other organs, expressed by both the whole organ and 100 mg of
      tissues. Results show that there might occur some specific binding sites for
      apoCIII on liver cells.

PMID- 8150433
TI  - [PCR amplification of the leptospiral DNAs from different genus and species with
      the variable sequences of 16S rRNA gene].
AB  - We designed a pair of primers from the variable regions (V2 and V4) of 16S rRNA
      gene of Leptospira interrogans, i. e. PI: 5'GGG AAC CTA ATA CTG GAT GG; PII: 5'
      ACA TAG TTT CAA GTG GAG GC, and amplified the leptospiral DNAs from different
      genus and species. When denaturing with 55 degrees C, all DNAs of L. interrogans
      had the same products not only in length but also with Kpn I-digested pattern.
      The DNA of L. biflexa could be amplified with a c. a. 280 bp-band but not
      digested by Kpn I, while the DNAs of Leptonema and other control bacteria had no
      amplification. In addition, the products of L. interrogans spp. could be
      hybridized with the PCR product of L. interrogans serovar lai strain Lai labelled
      with 32P, while the product of L. biflexa had no hybridization. It proved that
      the 16S rRNA gene primers is useful for the classification and detection of
      leptospires.

PMID- 8150434
TI  - [Heterogeneity of the immunoreactivity of A14, A19, B16 and B26- (125I)
      monoiodoinsulin to different species of anti-insulin immuno sera].
AB  - By using lactoperoxidase oxidation with 6 mol. urea in the reaction medium, the
      four tyrosine residues contained in insulin molecule were iodinated as
      monoiodoinsulins. These tracers, namely A14, A19, B16 and B26- (125I)
      monoiodoinsulins were separated with polyacrylamide gel electrophoresis+QAE
      Sephadex A25 chromatography. The present study demonstrated that the
      radiochemical purity of these tracers was high (> 98%) and the specific
      radioactivity also high. The binding of these tracers to surplus insulin antibody
      was more than 95%. These our tracers were tested in two RIA systems against 35
      species of guinea-pig anti-insulin immuno sera to compare their immunoreactivity
      (Ka, Scatchard analysis) to each immunoserum. The two RIA systems were antibody
      dilution and self displacement, and in both of them, only iodinated insulin and
      insulin antibody were present in the reaction fluid. The results showed that for
      16 antiinsulin immuno sera, Ka for A14, A19, B16 or B26-monoiodoinsulin were
      significantly different, and for the rest 19 immuno sera no significant
      difference could be detected. The possible mechanism and implication of this
      phenomenon were discussed.

PMID- 8150435
TI  - [Study on compound levonorgestrel microspheres].
AB  - Levonorgestrel (LNG) and estradiol (E2) were mixed in the ratio of 5:2 by weight.
      Compound LNG gelatin-microspheres were prepared by phase-separation method,
      natural biodegradable gelatin being used as the core material. The experimental
      conditions were optimized, the mean diameter of the microspheres obtained being
      10-40 microns, and the rate of encapsulation 65-75%. Storage observations and
      acceleration tests of the compound LNG gelatin-microsphere injection prepared
      showed that the microspheres have good stability. The thermal degradation
      activation energy of the injection was determined to be 134.4 kJ/mol, based on
      differential scanning colorimetry (DSC). T1/2 values for dissolution in vitro of
      LNG and E2 from the compound LNG gelatin-microsphere injection and from the
      unencapsulated injection showed significant difference (P < 0.01), indicating
      that the microspheres have good sustained release action. Effects of the pure LNG
      microsphere injection and compound LNG microsphere injection on the mouse ovary
      were compared histologically. The results showed that the compound LNG
      microsphere injection reduced some of the side effects such as ovary congestion.
      This points out that the compound dosage form can clinically alleviate the
      irregular bleeding caused by the administration of LNG alone.

PMID- 8150436
TI  - [An observation of the anticarcinogenic effect of mitoxantrone
      polybutylcyanoacrylate-nanosperes].
AB  - This paper reports the result of an experiment on the anticarcinogenic effect of
      liver targeted drug delivery system-mitoxantrone-polybutylcyanoacrylate
      nanospheres (DHAQ-PBCA-NS) by using a model of heterotopic and orthotopic
      transplantation of human hepatocellular carcinoma (HCC) in nude mice. No
      significant difference was noted between the anti-HCC effects of mitoxantrone and
      dexerubicin, but the anti-orthotopic transplanting HCC effect of mitoxantrone
      nanospheres was obviously higher than that of mitoxantrone and dexerubicin by
      comparison of tumor inhibition rates and proliferating cell nuclear antigen
      (PCNA). The result showed the applicability of mitoxantrone-nanospheres.

PMID- 8150437
TI  - [Determination of apparent pharmacokinetic parameters of shengfu injection by
      acute mortality of mice].
AB  - Apparent pharmacokinetic parameters of Shengfu injection, a first-aid traditional
      Chinese medicine, were determined by acute mortality of animals. The results
      suggested that the pharmacokinetics of Shengfu injection accords with the two
      compartment open model, and t1/2 alpha = 0.063h, t1/2 beta = 2.70h. The process
      of distribution was quite rapid, and the process of elimination was slow.

PMID- 8150438
TI  - [Synthesis of protected active peptide analogues of cholecystokinin and study of
      their biological activities].
AB  - A number of protected active peptide analogues of Cholecystokinin were prepared
      in solution by N-end stretching method with active esters. In the synthesis t
      butoxycarbonyl (Boc-) and benzyloxycarbonyl (Z-) were applied as protecting
      groups. Six oligopeptides which contained protecting groups have not yet been
      reported in literature. Their structures were identified by amino acid analysis,
      opticity, IR and FAB-MS. The results of preliminary pharmacological tests show
      all the samples have biological activities in various degrees.

PMID- 8150439
TI  - [Spiral shaped bacteria in the human gastric biopsy].
AB  - Biopsy specimens from the gastric mucosa of 149 patients who underwent
      gastroduodenal endoscopy for upper gastrointestinal complaints were studied by
      light microscopy and culture. Spiral shaped bacteria were detected in four of the
      specimens by smears with Gram stain. The positive rate was 2.68%, but these
      bacteria and HP did not grow in culture. The characteristic helical morphology of
      the bacteria appears to be similar to that of the bacteria found in the stomach
      of cats and dogs. And what of significance in these cases is the presence of
      spiral shaped bacteria in association with chronic gastritis.

PMID- 8150440
TI  - [Effect of SC1001-sodium on ADA activity of the thymus, spleen and brain in
      repeated seizure rats].
AB  - Twenty nine adult SD rats in the experiment were randomly separated into two
      groups. Nineteen rats of them were intramuscularly injected (i.m.) with Coriaria
      lactone (CL, 2.5 mg/kg for female rat; 30 mg/kg for male rat) two days a time,
      continued 28 times, to induce repeated seizures, as the experimental group. The
      control group (n = 10) was injected with normal saline (N.S.) in the same volume
      as that of CL. The rats of experimental group were subdivided into a treatment
      group (n = 9) with SC1001Na (200 mg/kg) and a placebo group (n = 10) receiving
      N.S. in the same volume as that of SC1001 Na. All rats of repeated seizure were
      administered once every day for a week. The results indicated that SC1001Na (200
      mg/kg) could inhibit in some degree the growth of immune organs (spleen and
      thymus) and significantly decrease the ADA activity of thymus, cerebrum and
      cerebellum, suggesting that the antiepileptic mechanism of SC1001Na is probably
      related with the decreased activity of ADA and the increased adenosine level in
      brain.

PMID- 8150441
TI  - [Effect of propranolol on circadian rhythm of Goldblatt hypertension in goat].
AB  - With the Goldblatt two-kidney two-clip method, persistent hypertension was
      reproduced in 7 goats. After hypertension was established and stabilized, a beta
      receptor inhibitor Propranolol was given to the goats in the usual form of drug
      administration (20 mg, q 8 h) or in the form of chronotherapy (30 mg, QN). The
      mean value of BP was computed. The result suggested that, compared with the usual
      form of therapy, chronotherapy could reduce the hypertension to the same degree,
      but with less time and less amount of drug.

PMID- 8150442
TI  - [Analysis of trace elements in scalp hair of healthy people, breast cancer and
      hyperplasia patients with XRF method].
AB  - The trace element analysis on the scalp hair of patients with breast cancer and
      hyperplasia was made using the XRF method and compared with that of healthy
      people. The hair samples from 42 breast cancer patients, 57 hyperplasia patients
      and 31 healthy people were collected respectively. The results showed that Mn, Cr
      and K content in the hair of the patients with cancer was much higher than that
      of the normal (P < 0.05). Significant differences were also found between
      patients with breast cancer and with hyperplasia in K and Fe content. The former
      was much higher than the latter (P < 0.05).

PMID- 8150443
TI  - [Quantitative study of transmitral flow by spectral Doppler echocardiography].
AB  - The aim of this study is to find an accurate and simple method for measuring the
      transmitral flow by pulsed Doppler echocardiography (PDE). Four parameters were
      measured: (1) anteroposterior dimension of the mitral valve annulus (MVA) (a);
      (2) mediolateral dimension of MVA (b); (3) a and b of MVA to calculate the area
      of MVA (elliptical method); (4) the area of the mitral valve orifice (MVO). The
      transmitral flow calculated by the use of (3) and (4) were compared with the
      aortic blood flow. The findings suggested that the MVA calculated with elliptical
      method is accurate and simple in measuring the transmitral flow.

PMID- 8150444
TI  - [Study on respiratory mechanics in soldiers].
AB  - A study of the maximal expiratory flow volume (MEFV) curve, chord time constant
      (tau ch), specific time constant (S tau) and partial mean transit time (MTTp) in
      104 soldiers stationed in Chengdu was made by "point-measured method". Results
      showed that in comparison with the predicted value, the flow at high lung volume,
      V75 was increased; tau ch75, S tau 75 and MTT20-30% at the corresponding lung
      volume were shortened; V25 and FEF75-85% at the low lung volume were lowered; and
      V25, S tau 25, MTT70-80% at the same volume were prolonged. Five normal sedentary
      workers received a FVC training for a period of one month. The result showed that
      FVC, FEV1 and V75 were significantly increased, and that the changes just
      corresponded to those in trained soldiers. All the facts suggested that the
      respiratory muscles in soldiers were trained and their activities were
      strengthened by the military training. The changes in respiratory mechanics just
      after exercise show that the increased V75, enlarged tidal volume and quickened
      tidal flow lead to the deepening and quickening of respiration and increasing of
      ventilation. Resembling exercise, these changes of military training are
      available for oxygen requirement during the training.

PMID- 8150446
TI  - [Computed tomography in the diagnosis of intracranial trigeminal neuroma].
AB  - CT scans of 12 cases of intracranial trigeminal neuroma were presented. Three of
      the neuromas were located in petrous apex-middle cranial fossa, two in posterior
      cranial fossa, and 7 in both the middle and posterior cranial fossae. The tumors
      appeared hypo- and isodense on the plain CT scan. After contrast infusion, all
      tumors were well circumscribed with marked enhancement, which was homogeneous,
      inhomogeneous or circular. None of the trigeminal neuroma had surrounding brain
      edema. Of 12 cases, 10 showed change of cranial bones, which included dilatation
      of Meckle's cave and destructions of petrous apex, clivus and the bottom of
      middle cranial fossa. The tumor in one case extended to paranasopharyngeal space
      from the bottom of middle cranial fossa, Various features of trigeminal neuroma
      on CT were reviewed. Also presented were the author's experiences in
      differentiating intracranial trigeminal neuroma from meningiom, from pituitary
      adenoma spreading to parasella and glioma adjacent to cranial bottom in middle
      cranial fossa, and from acoustic neuroma, meningioma, cholesteatoma in
      cerebellopontine angle.

PMID- 8150445
TI  - [Changes in TXB2/6-keto-PGF1 alpha ratio and their relation to blood lipids of
      Type A behavioral patterns].
AB  - To study the pathophysiological relation between Type A behavioral pattern and
      coronary artery disease, we analyzed the Type A behavioral pattern, serum
      triglycerides (TG), cholesterol (TC), high density lipoprotein cholesterol
      (HDLc), and TXB2, 6-keto-PGF1 alpha in 60 patients with coronary artery disease
      and 60 age-sex-matched healthy subjects. All of them had normal blood pressure.
      The results showed Type A behavioral pattern was more prevalent than Type B
      behavioral pattern in coronary artery diseased patients and the reverse was true
      in the controlled subjects (P < 0.025); TG, TC and TXB2/6-keto-PGF1 alpha ratio
      increased significantly in Type A behavioral pattern compared with Type B
      behavioral patients, but HDLc/(TC+TG) and the level of HDLc decreased
      significantly in the Type A behavioral pattern than in the Type B behavioral
      pattern (P < 0.05). The TG, TC increased significantly and 6-keto-PGF1 alpha HDLc
      decreased significantly in the coronary artery diseased patients (P < 0.05).
      However, the ratio of TXB2/6-keto-PGF1 alpha was inversely related to
      HDLc/(TC+TG) among the coronary artery diseased patients. The results of this
      cross-sectional study suggest that coronary artery disease is associated with
      Type A behavioral pattern through the metabolism of lipids and prostaglandins in
      various ways.

PMID- 8150447
TI  - [A cephalometric study on determining the orientation of occlusal plane].
AB  - A study of the parallel relationship between the occlusal plane and the line
      connecting nasal alar and tragus was made in 90 dentulous cases by using
      cephalometry. The results show that the line connecting the inferior point of
      nasal alar and the mid-point of tragus runs much more parallel with the occlusal
      plane. The regression equation reveals a "line of closest fitting". It was used
      in the prosthetic treatment for 50 edentulous patients with good clinical
      results. The line connecting the inferior point of nasal alar and the mid-point
      of tragus therefore represents a proper reference plane for determining occlusal
      plane and hence should be still a valuable index in clinical dentistry.

PMID- 8150448
TI  - [Pleural malignant mesothelioma complicated with disseminated intravascular
      coagulation].
AB  - Three cases of MPM complicated with DIC were reported in a total of 6862
      autopsies (0.04%) from 1950 to 1989 year in our university hospital. All the
      three cases showed hemorrhagic patches, shock, decreased platelets and
      fibrinogen, and prolonged prothrombin and thrombin time. Hyaline thrombosis was
      observed in the pulmonary interstitial microvessels. We have also discussed the
      diagnosis and pathogenesis of DIC.

PMID- 8150449
TI  - [The preparation of 99mTc-NGA instant lyophilized kit for hepatic imaging].
AB  - The preparation of one-step kit for the 99mTc labelled galactosyl-neo
      glycoalbumin (NGA) using SnCl2 reduced method was reported in this paper. We
      developed a method of quality control and established the optimum scheme of
      technetium labelling on the basis of exploring the effects of varied labelled
      conditions on radiochemical purity. Our data indicates : (a) the kit is sterile,
      pyrogen-free and no toxic effects; (b) the operation is simple and fast; (c) its
      period of validity lasts no less than 3 months; (d) the radiochemical purity >
      95%; (e) the stability of 99mTc-NGA in vitro > 4 hours; (f) the results of animal
      imaging and clinical probation are satisfactory.

PMID- 8150450
TI  - [A model of orthotopic transplantation of human hepatoma established in nude mice
      tumor inhibition studies].
AB  - We established a model of orthotopic transplantation of human hepato-carcinoma.
      The tissues from human hepatoma LTNM4 were surgically implanted into the livers
      of 32 BALB/c nu/nu nude mice. These led to the development of tum or masses in
      the livers of 31 nude mice; the rate of success was about 96.8% (31/32).
      Furthermore, this model was applied to the studies on the tumor inhibitory action
      of DHAQ-PBCA-NS, a hepatic targeting preparation for anticarcinoma. Satisfactory
      effect was attained. The result has proved the applicability of this animal model
      to researches on hepatic targeting preparations against carcinoma.

PMID- 8150451
TI  - [Positive identification of the specificity of polymerase chain reaction
      product].
AB  - A method of positive identification of the specificity of polymerase chain
      reaction (PCR) product using internal oligonucleotide probe is introduced. The
      hybridization was done on the agarose gel which was dried after electrophoresis.
      Detection of the expression of T cell receptor a chain variable (TCR V alpha)
      genes on mRNA level was used as the experimental model. Twenty nine TCR V alpha
      gene subfamilies could be distinguished clearly in healthy human peripheral blood
      lymphocytes by this method. Positive identification of PCR product on dried
      agarose gel by internal oligonucleotide probe is relatively simple and less time
      consuming.

PMID- 8150452
TI  - [Determination of ceftizoxime in serum by high performance liquid
      chromatography].
AB  - This paper reports the determination of ceftizoxime, a new cephalosporin
      antibiotic, in serum by RP-HPLC. The technique for serum protein precipitation by
      adding perchloric acid is adapted for sample preparations. After centrifugation,
      a 100 microliters portion of aqueous phase is injected into chromatographic
      column of ultrasphere CN, the mobile phase being a mixture of methanol and 1%
      acetic acid (15:85). The standard curve is linear within the range of 2.5-120
      mg/L in serum. The detection limit of ceftizoxime in serum stands at 0.1 mg/L.
      The recoveries from serum samples after protein precipitation reach 95.4-96.3%.
      The within day CVs and interday CVs are 2.7-3.3% and 4.8-7.6%, respectively. This
      method is rapid, reliable and reproducible. It has been utilized to measure the
      concentration of ceftizoxime in patient serum for clinical research and
      pharmacokinetic studies.

PMID- 8150453
TI  - Immunopathology of malignant mesothelioma.

PMID- 8150455
TI  - Augmentation of fetal granulopoiesis with chorioamnionitis during the second
      trimester of gestation.
AB  - Chorioamnionitis is a major hazard to pregnancy in the second trimester. It
      affects the fetomaternal unit, causing febrile illness in the mother. The fetus
      eventually is expelled because uterine contractions can no longer be suppressed
      after a certain stage of the disease. To determine the effects of
      chorioamnionitis on the fetus we examined fetal hematopoiesis, which is, for the
      most part, located extramedullarily during the second trimester of gestation. The
      study was performed morphometrically on sections of fetal tissues; the results
      are given as an increase of cells per square millimeter. In chorioamnionitis the
      fetuses (n = 18) showed increased granulopoiesis in the parenchyma of the liver
      (x12), in the spleen (x 5), in the portal triads of the liver (x3), and in the
      bone marrow (x1.35). Erythropoiesis and total hematopoiesis were reduced in all
      compartments. Inflammatory disease in the mother other than chorioamnionitis did
      not alter fetal hematopoiesis (n = 13). Under normal conditions fetal liver
      granulopoiesis is at a very low level within the sinusoids, but an early and
      substantial increase can be seen most easily in this location during infection;
      chorioamnionitis can thus be diagnosed from the fetal liver alone. Alterations in
      fetal hematopoiesis might be caused by cytokines generated at the fetomaternal
      interface during chorioamnionitis.

PMID- 8150454
TI  - Incidence of Epstein-Barr virus bcl-2 expression and chromosomal translocation
      t(14;18) in large cell lymphoma associated with paragranuloma (lymphocyte
      predominant Hodgkin's disease).
AB  - Seven cases of large cell lymphoma (LCL) developing simultaneously or secondarily
      to lymphocyte-predominant Hodgkin's disease (nodular paragranuloma [NP]) were
      investigated for the presence of Epstein-Barr virus genomic material and the
      chromosomal translocation t(14;18) involving the major breakpoint region of the
      bcl-2 gene using the polymerase chain reaction on paraffin-embedded material. The
      translocation t(14;18) and Epstein-Barr virus could not be demonstrated in any
      case. The expression of the bcl-2 oncogene product was investigated using
      immunohistochemistry. Only in one case were the lymphocytic and histiocytic cells
      positively stained with the bcl-2 antibody, whereas the associated LCL
      demonstrated a completely negative immunoreaction. In another case the LCL had a
      positive immunoreaction with this antibody and the corresponding lymphocytic and
      histiocytic cells were completely negative. We conclude that Epstein-Barr virus
      infection is rare or absent in NP and in the LCLs associated with NP. The
      chromosomal translocation t(14;18) does not seem to be a factor in the
      transformation of NP into LCL.

PMID- 8150456
TI  - Systemic lymphadenopathic histology in human immunodeficiency virus-1
      seropositive drug addicts without apparent acquired immunodeficiency syndrome.
AB  - We examined lymph nodes from multiple sites in 50 individuals infected with human
      immunodeficiency virus (HIV-1) who died accidentally of drug overdoses and in
      whom there was no evidence of opportunistic infection. The size, histologic
      pattern, presence of Warthin-Finkeldey-type giant cells, and estimation of CD4
      cell count of these lymph nodes were compared with those of 13 seronegative drug
      addicts (controls). Lymph nodes from seropositive individuals were slightly but
      significantly larger than those of controls. Lymph nodes from seropositive cases
      were much more likely to contain secondary follicles (90%) than were those from
      controls (20%). Unlike follicles in control nodes, most secondary follicles in
      the seropositive cases were in various stages of fragmentation and involution. As
      follicular changes progressed, there was a decrease in CD4 cells and an increase
      in intrafollicular and paracortical plasma cells. Plasmacytosis was much more
      prevalent in lymph nodes from seropositive individuals than in controls. Warthin
      Finkeldey-type giant cells were present in at least one node in 29 of 50
      seropositive cases, were most numerous in those showing follicular hyperplasia
      with fragmentation (45% of cases), and were especially numerous in Peyer's
      patches (61% of cases). There was generally good concordance of HIV-1-associated
      follicular morphology among diverse lymph node groups. There is prolonged
      generalized, mild hyperplastic lymphadenopathy with frequent syncytial cells in
      intravenous drug addicts with asymptomatic HIV-1 infection.

PMID- 8150457
TI  - A comparative study of flow cytometry and histopathologic findings in thyroid
      follicular carcinomas and adenomas.
AB  - As a possible diagnostic aid in the often difficult histopathologic distinction
      of thyroid follicular carcinomas from adenomas based on invasion most flow
      cytometry studies have indicated a higher aneuploidy incidence in carcinomas.
      However, these reports often are difficult to analyze mainly due to nonuniformity
      of pathologic diagnostic criteria. The present study compares the flow cytometry
      results of 65 follicular tumors with pathologic findings based on the World
      Health Organization's specific diagnostic and staging criteria. Aneuploidy was
      significantly higher in the 28 cancers than in the 27 hypercellular (fetal and
      embryonal) adenomas (57% v 22%; P = .02). There was a high percentage of
      aneuploidy (75%; nine of 12 cases) in the widely invasive follicular carcinomas,
      compared with 40% (six of 15 cases) in the minimally invasive carcinomas, 22%
      (six of 27 cases) in the hypercellular adenomas, and 10% (one of 10 cases) in the
      normofollicular or macrofollicular adenomas. However, aneuploidy was not
      significantly different between the most difficult differential histopathologic
      diagnoses of minimally invasive follicular carcinoma (40%; six of 15 cases) and
      hypercellular adenoma (22%; six of 27 cases) (P = .12). Other data included
      relatively high frequencies of aneuploidy in hypercellular adenomas (29%; six of
      21 cases) and diploid status of carcinomas (36%; 12 of 33 cases). In summary,
      although the overall findings show a trend toward increasing aneuploidy from well
      differentiated and hypercellular adenomas to minimally and widely invasive
      follicular carcinomas, the aneuploidy data are inconsistent and indicative of its
      nonspecificity and limited diagnostic usefulness.

PMID- 8150458
TI  - Light and electron microscopic features of the liver in mucopolysaccharidosis.
AB  - The mucopolysaccharidosis (MPS) diseases lead to the accumulation of
      glycosaminoglycan in many tissues. In this study 19 MPS I, one MPS II, five MPS
      III, and two MPS VI patients underwent liver biopsy for light and electron
      microscopic examination. Electron microscopy was performed for all 27 specimens.
      Twenty-six specimens were studied by light microscopy, and the slides were
      stained with colloidal iron and alcian blue in 26 and six biopsy specimens,
      respectively. By hematoxylin-eosin stain 20 of 26 cases showed hepatocellular
      dilatation with rarefaction of the cytoplasm; the Kupffer cells were
      unremarkable. Twenty-four and 25 of the 26 biopsy specimens showed substantial
      colloidal iron staining of hepatocytes and Kupffer cells, respectively. The six
      biopsy specimens prepared with alcian blue stain showed no reactivity of any cell
      type. Electron microscopy revealed characteristic membrane-bound inclusions
      within the hepatocytes and Kupffer cells of all 27 biopsy specimens. Of 19 cases
      in which Ito cells were identified, 18 included cells containing similar
      inclusions. Twenty of 27 biopsy specimens also demonstrated the hepatocellular
      accumulation of lipid droplets. Although there were no absolute distinguishing
      features among the various MPS diseases, the two MPS VI cases showed
      glycosaminoglycan inclusions that were fewer in number, smaller, and contained
      more abundant lipofusion than those associated with the other MPS types.

PMID- 8150459
TI  - Analysis of clonality in archival tissues by polymerase chain reaction
      amplification of PGK-1.
AB  - Clonality of archival formalin-fixed tissue sections was analyzed by polymerase
      chain reaction amplification of a portion of the X-linked phosphoglycerate kinase
      (PGK-1) gene. Amplification was successful in 29 of 36 cases of uterine
      endometrioid adenocarcinoma. Five of these cases, including both tumor and
      control tissue from the same patients, were heterozygous for the BstXI
      polymorphic site of the PGK-1-amplified product, permitting analysis of
      clonality. Pretreatment of the DNA with HpaII blocked amplification of one of the
      two PGK-1 alleles from four of five cases of tumor, indicating the clonal pattern
      of X chromosome inactivation in these cases. In contrast, in DNA from paired
      control tissues HpaII pretreatment had no effect, indicating a random pattern of
      X chromosome inactivation in normal tissue. One of the cases of endometrioid
      adenocarcinoma contained a high proportion (45%) of nontumor cells, precluding
      the determination of clonality. We conclude that polymerase chain reaction
      amplification can be used for the determination of the pattern of X chromosome
      inactivation in formalin-fixed tissue sections. Such an approach makes it
      feasible to include specimens from archival tissue collections in the analysis of
      clonality.

PMID- 8150460
TI  - Invasive cavitary pulmonary aspergillosis in patients with cancer: a
      clinicopathologic study.
AB  - We studied the histopathology and clinicopathologic correlates of invasive
      cavitary pulmonary aspergillosis in 11 immunosuppressed patients with
      disseminated malignancy. In most patients cavities were produced by separation of
      necrotic from viable lung, resulting in an intracavitary sequestrum ("lung
      ball"). Central dissolution of large necrotic areas and suppurative granulomatous
      aspergillary pneumonia were additional causes of cavities in three patients. In
      four patients with chronic cavities sequestra had been replaced by intracavitary
      mycetomas ("fungus balls"). Neutrophils usually were numerous at the interface of
      the sequestrum and adjacent lung, but were minimally present in three patients
      with prolonged severe neutropenia. The lack of neutrophils in some patients
      suggests that factors other than neutrophil-derived proteases may be important in
      cavity formation. A prominent giant cell reaction was seen in three patients with
      chronic cavities. Hemoptysis occurred in five patients and massive hemoptysis due
      to a bronchoarterial fistula caused the death of one patient. The "air-crescent"
      sign was not observed radiographically in any patient and is therefore considered
      to be an insensitive marker for lung cavitation in invasive aspergillosis.
      Persistent intracavitary fungal growth may serve as a reservoir for recurrent
      fungal invasion in patients with prolonged or repeated episodes of severe
      neutropenia.

PMID- 8150461
TI  - Ewing's sarcoma--routine diagnostic utilization of MIC2 analysis: a Pediatric
      Oncology Group/Children's Cancer Group Intergroup Study.
AB  - Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) are small blue cell
      tumors with no reliable positive diagnostic markers. However, Ewing's sarcoma and
      PNET recently have been shown to strongly express an antigen determined by the
      MIC2 gene, whereas other blue cell tumors of childhood for the most part do not.
      MIC2 analysis therefore offers a distinctive addition to the panel of
      immunohistochemical stains used to differentiate among small blue cell tumors of
      childhood, since it represents the first positive marker for Ewing's sarcoma and
      PNET. This study addresses the reliability of MIC2 analysis using the monoclonal
      antibody 12E7 on tumors registered in the current Intergroup Ewing's Sarcoma
      protocol. Of 244 tumors, 221 (91%) showed a diffuse strong membranous pattern.
      The antibody appears to withstand all the fixation variables inherent in a multi
      institutional study. We conclude that MIC2 expression is highly reliable as a
      positive marker for the Ewing's sarcoma/PNET family of tumors when the results
      are interpreted in the total context with clinical and pathologic parameters.

PMID- 8150462
TI  - Diagnostic criteria and histologic grading in multiple myeloma: histologic and
      immunohistologic analysis of 176 cases with clinical correlation.
AB  - Diagnostic criteria in myeloma have not been completely standardized or tested
      for accuracy; furthermore, marrow findings of prognostic value have not been
      clearly identified. We studied 176 patients with myeloma to determine the
      relative value of marrow differential, tissue sections, and immunohistology
      singly or in concert in the diagnosis of myeloma and to correlate morphologic
      features with prognosis. Controls were patients with benign marrow plasmacytosis.
      Homogeneous nodules of plasma cells at least 1/2 high-power field and/or
      monotypic aggregates of plasma cells filling at least one interfatty marrow space
      correctly identified myeloma in 83.5% of cases, with no false positives. The
      current numerical criteria of marrow plasmacytosis > or = 10% occurred in 17.1%
      of the controls, and 39.7% of patients with myeloma had less than 10% marrow
      plasmacytosis at presentation. Myeloma was graded histologically into categories
      of none/minimal, moderate, and marked dysplasia on the basis of dysplastic
      features and mitoses; these categories correlated well with clinical outcome,
      with median length of survival of 32.9, 25.2, and 12.9 months, respectively
      (overall median length of survival of 123 patients with myeloma, 29.2 months).
      Packing of marrow by tumor and mitoses measuring at least 5/high-power field
      regardless of grade also was associated with a poor prognosis (median lengths of
      survival, 15.2 and 11 months, respectively). Myeloma may be diagnosed in the
      great majority of cases by demonstrating homogeneous nodules and/or monotypic
      aggregates of plasma cells in the marrow. Prognostic features were shown to
      include marked dysplasia, mitoses, packing of marrow by tumor, and clinical
      stage.

PMID- 8150463
TI  - Early recurrence of chronic active myocarditis after heart transplantation.

PMID- 8150464
TI  - EBNA2 expression in nasopharyngeal carcinoma.

PMID- 8150465
TI  - Left anterior descending coronary artery: ischemia and sudden death.

PMID- 8150466
TI  - Gastric adenocarcinoma with ciliated tumor cells.

PMID- 8150467
TI  - Dentistry overseas--an international volunteer program.

PMID- 8150468
TI  - Being a leader makes a difference.

PMID- 8150469
TI  - Successful financial arrangements: a team approach.

PMID- 8150470
TI  - Hospital restructuring: good news or bad?

PMID- 8150471
TI  - Overview: healthcare, the final frontier going where no nurse has ever gone
      before.

PMID- 8150472
TI  - Getting nursing's message into the media.

PMID- 8150473
TI  - Building a profession together.

PMID- 8150474
TI  - Changing nursing image through the media.

PMID- 8150475
TI  - Projecting your best professional image.

PMID- 8150476
TI  - The future of minorities in military nursing.

PMID- 8150477
TI  - Merilyn Francis. Interview by Jessica Bell.

PMID- 8150478
TI  - The Hispanic population and nursing: past, present, and future trends.

PMID- 8150479
TI  - The positive side of role reversal.

PMID- 8150481
TI  - "My most humorous moment in nursing".

PMID- 8150480
TI  - Nurses and manufacturers: sharing knowledge and experience for better health
      care.

PMID- 8150482
TI  - Getting rid of Sairy Gamp: nursing & feminism.

PMID- 8150483
TI  - Everything you always wanted to know about graduate nursing education.

PMID- 8150485
TI  - Nursing organizations.

PMID- 8150484
TI  - Success in your first interview.

PMID- 8150486
TI  - Ten tips to help your self-confidence.

PMID- 8150487
TI  - Nursing after graduation: reflections from a recent grad.

PMID- 8150488
TI  - Reflections from a 20th anniversary grad.

PMID- 8150489
TI  - What's wrong with this picture?

PMID- 8150491
TI  - Questions and answers on the computerized NCLEX-RN exam.

PMID- 8150490
TI  - Where in the world are the new grad jobs?

PMID- 8150492
TI  - The great flood of '93.

PMID- 8150493
TI  - Jaime Burmeister. Interview by Jessica Bell.

PMID- 8150494
TI  - Julie Supple. Interview by Jessica Bell.

PMID- 8150495
TI  - Nursing, unrestricted by considerations of...

PMID- 8150496
TI  - Trust and betrayal.

PMID- 8150497
TI  - What year is it, anyway?

PMID- 8150498
TI  - Volunteering for disaster nursing.

PMID- 8150499
TI  - Health care reform legislation.

PMID- 8150500
TI  - Incest: the hidden abuse.

PMID- 8150501
TI  - Sexual harassment in nursing school.

PMID- 8150502
TI  - Violence against women: implications for nursing practice.

PMID- 8150503
TI  - Elder abuse.

PMID- 8150504
TI  - Getting the most from group study sessions.

PMID- 8150505
TI  - Getting the most out of clinical classes.

PMID- 8150506
TI  - A little rose.

PMID- 8150507
TI  - Effects of osseointegrated implants on psychological and social well-being: a
      comparison with replacement removable prostheses.
AB  - Sixty-one patients participated in a longitudinal study designed to compare the
      psychological effects of osseointegrated implants with those of conventional
      denture replacements. Thirty-two patients who requested either relining or
      reconstruction of their dentures were asked to complete questionnaires designed
      to measure their psychological well-being while they were on a waiting list and
      then again 6 months after treatment. Their responses were compared with those of
      29 patients who had received an osseointegrated implant. While the implant
      patients had reported significant declines in psychological distress, there was
      no such change for the denture patients. Although both groups experienced fewer
      disabling symptoms, the decline was greater for the implant group. Finally,
      neither group showed evidence of any change in self-esteem. The results suggest
      that osseointegrated implants can have a more positive effect on well-being than
      denture replacements.

PMID- 8150508
TI  - Phenytoin hyperplasia occurring in relation to titanium implants: a clinical
      report.
AB  - Dilantin sodium is a commonly used anticonvulsive agent. A well-known side effect
      of this medication is hyperplasia of gingival tissues. This hyperplasia has also
      been reported in mucosa beneath complete dentures and has been related to poor
      oral hygiene. This case report describes hyperplasia of tissues around titanium
      implants in a patient taking Dilantin sodium to prevent epileptic seizures. The
      excess tissue was removed and hygiene reinforced. No recurrence of the tissue
      enlargement is evident after 1 year.

PMID- 8150509
TI  - Healing pattern of bone regeneration in membrane-protected defects: a histologic
      study in the canine mandible.
AB  - In this study, standard and prototype reinforced e-PTFE membranes were used to
      evaluate the pattern of bone regeneration in membrane-protected defects in the
      mandibles of four dogs. Following a healing period of 2 and 4 months, control
      sites without membranes exhibited incomplete osseous healing with a persisting
      defect. Test sites with membranes demonstrated significantly better bone healing,
      although bone regeneration was not yet completed at 4 months. The histologic
      evaluation showed that bone regeneration, once activated, progresses in a
      programmed sequence through a series of maturation steps, which closely resemble
      the pattern of bone development and growth.

PMID- 8150510
TI  - The use of e-PTFE barrier membranes for bone promotion around titanium implants
      placed into extraction sockets: a prospective multicenter study.
AB  - This multicenter study was conducted to determine the predictability for implants
      placed into immediate extraction sockets and augmented with e-PTFE barrier
      membranes. Forty-nine implants were placed in immediate extraction sockets.
      Initial and final defect measurements and the number of threads exposed were
      compared. Patients were followed up to 1 year after implant loading. Three
      implants were lost at the abutment connection surgery. The 1-year survival rate
      was 93.9%. Twenty barrier membranes became exposed and were removed prior to
      stage 2 surgery, while the remaining barriers were removed at abutment
      connection. The average defect bone formation for membrane-retained sites was 4.8
      mm, while the average bone formation for sites in which the membranes were
      prematurely removed was 4.0 mm (P < .0001). At stage 2 surgery there was an
      average of 0.6 threads exposed (P < .001) for the membrane-retained sites and 2.6
      threads for the early removal sites (NS). Forty-five pairs of nonstandardized
      radiographs were evaluated for bone loss after implant loading (average 7.5
      months). The mesiodistal bone loss averaged 0.72 mm. Within the limits of this
      study, e-PTFE membranes will promote clinically and statistically significant
      amounts of bone around immediately placed implants. Retention of e-PTFE barriers
      until stage 2 surgery improves the amount of bone promoted around the implants.

PMID- 8150511
TI  - An in vivo evaluation of an osteoinductive implantable material produced by
      osteoblastic cells in vitro.
AB  - Osteoinductive implantable materials have been a subject of basic science
      research in clinical implantology. This study examined the osteoinductive effect
      of an implantable material produced by osteoblastic cells that were isolated in
      the laboratory from mouse calvaria. After 21 days in culture, osteoblastic cells
      formed a thin film that could be easily manipulated. This thin film was subjected
      to freezing and thawing and was implanted in mouse muscle tissue. Osteoblastic
      cells were strongly positive for alkaline phosphatase reactivity and Von Kossa
      stain in vitro. Collagen type I, osteocalcin (BGP), and alkaline phosphatase were
      identified at the immunohistochemical electron microscopic level. Histologic
      findings showed an osteoinductive effect of the implanted material. The results
      strongly suggest the possibility of producing an osteoinductive implantable
      material by culturing osteoblastic cells in vitro.

PMID- 8150512
TI  - Osseointegrated implants for single-tooth replacement: progress report from a
      multicenter prospective study after 3 years.
AB  - After 3 years, 82 of the original 92 patients remain in this prospective
      multicenter study of single-tooth restorations supported by Branemark implants.
      Since the 1-year follow-up, 6 more patients have been lost, but no additional
      implants have failed in those patients examined at the 3-year follow-up visit.
      After 1 year of function, 97.2% of the implants survived in 88 patients, and
      between the 1- and 3-year follow-up, 100% survived in 82 patients, giving a 3
      year cumulative success rate of 97.2%. No changes were observed in the status of
      gingivitis, pocket depth, periodontal pocket bleeding index, and tooth and
      implant mobility from those reported after 1 year. Marginal bone resorption
      remained at a low level--less than 0.1 mm annually during the second and third
      years. Abutment screw loosening continued, but at a significantly reduced rate
      from that reported after 1 year. When used, gold rather than titanium abutment
      screws remained secure.

PMID- 8150513
TI  - Mandibular implants and the growing patient.
AB  - The dynamic relation of the anteroposterior and rotational growth of the mandible
      to the transverse arch width and dental height changes must be understood before
      placing endosseous implants in actively growing patients. Research models
      demonstrate that osseointegrated implants lack the compensatory growth mechanism
      of the natural dentition. Remodeling associated with skeletal growth in the
      region of the implant placement site could cause the implant to either become
      unsupported by bone or submerged within it. Implants placed after age 15 in girls
      and 18 in boys have the most predictable prognosis. When placed in the growing
      patient, dental implants should be closely monitored and carefully restored with
      implant prostheses designed to accommodate growth and development.

PMID- 8150514
TI  - Oral tactile sensibility recorded in overdenture wearers with implants or natural
      roots: a comparative study. Part 2.
AB  - The capacity of dentate subjects to discriminate the thickness of objects placed
      between the teeth seems to depend on receptors in the periodontal ligament and
      muscles. The compensatory mechanism of ankylotic implants for the function of
      missing periodontal ligaments is not yet known. To investigate this question in
      overdenture wearers, 26 patients with ITI implants and 20 patients with natural
      roots were selected. According to the experimental protocol, the discriminatory
      ability was recorded with 10 steel foils (thickness ranging from 10 to 100
      microns) placed between the premolars. Each thickness was tested 10 times and the
      test subjects were required to distinguish whether foil was positioned between
      the teeth. A maximum of 100 correct or 100 incorrect answers was possible. The
      average number of incorrect answers was significantly higher in test subjects
      with implants. The 50% limit (ie, the tested thickness recorded with at least 5
      wrong answers) was established, but no statistically significant difference was
      found. In both groups, the critical tactile threshold of perceived thickness was
      30 to 40 microns, with 2 being the average number of incorrect assessments. When
      comparing the minimal thickness, which was recorded without incorrect assessment,
      a significantly lower threshold was observed on patients with natural roots.
      Thus, active tactile sensibility appears to depend on the receptors in the
      periodontal ligament. However, wearing of removable prostheses is a modifying
      factor and may influence the oral tactile sensibility for both groups.

PMID- 8150515
TI  - Comparison of surface characteristics of six commercially pure titanium
      abutments.
AB  - Clinical studies have reported a positive correlation between the surface
      roughness of teeth or implants and the rate of supragingival and subgingival
      plaque maturation. This study compared the surface characteristics of abutments
      from different implant systems (Astra Tech, Bonefit, Branemark, Core-Vent, IMZ,
      and Steri-Oss). For each system, two abutments were examined for surface
      roughness and surface hardness. The latter served as an indicator for resistance
      against roughening during professional or habitual oral hygiene procedures. The
      Ra values (in microns) of the tested abutments were: Steri-Oss, 0.10; IMZ, 0.14;
      Branemark, 0.21; Bonefit, 0.23; Astra Tech, 0.27; and Core-Vent, 0.30. The
      Vickers hardness scores (in VHN) were: Branemark, 154; IMZ, 208; Astra Tech, 258;
      Bonefit, 292; Core-Vent, 304; and Steri-Oss, 340. In comparison to most
      metallographically polished composites, titanium abutments showed a higher
      initial surface roughness and a slightly higher surface hardness. This may
      explain, besides the known high surface free energy of titanium, rapid plaque
      growth on these abutments.

PMID- 8150516
TI  - New connective tissue attachment formation on various biomaterials implanted in
      roots.
AB  - To determine whether connective tissue attachment can occur on implant materials
      by repopulating periodontal ligament (PDL)-derived cells and whether the new
      connective tissue attachments formation is influenced by the type of implant
      materials, periodontal tissue regeneration on four materials implanted into root
      cavities of cat canines was observed under conditions where PDL-derived cells
      could populate the surface of the materials. New connective tissue attachment
      occurred on bioactive materials such as bioglass and hydroxyapatite, while little
      or no cementum deposition was seen on bioinert materials such as titanium alloy
      and partially stabilized zirconium. Results showed that PDL-derived cells can
      form new connective tissue attachments on implant materials and that the
      formation of new connective tissue attachment is influenced by bioactivity of the
      materials.

PMID- 8150517
TI  - A new approach to restoring single-tooth implants: report of a case.
AB  - A technique was developed for the fabrication of an anterior single-tooth
      restoration supported by a malaligned endosseous implant. Patient treatment
      included the application of this original technique, which can be used in both
      anterior and posterior sections of the arch.

PMID- 8150518
TI  - Prosthodontic complications in osseointegrated dental implant treatment.
AB  - Complications were recorded in consecutive patients with osseointegrated implant
      supported prostheses visiting prosthodontic specialist clinics during October and
      November 1991. Patients at regular follow-ups and emergency visits were included.
      Of the 600 prostheses examined, 28% needed some prosthodontic treatment.
      Complications varied widely--from simple adjustment to complete remaking of the
      prosthesis. The most common complications observed were related to the acrylic
      resin part of the prostheses. The frequency was higher in maxillary than in
      mandibular prostheses, and in full-arch removable and fixed prostheses than in
      single-tooth replacements and fixed partial dentures. Implant losses were rare
      (0.3% of all 2,709 implants placed) and occurred in 1% of the patients examined.

PMID- 8150519
TI  - Characteristics associated with the loss and peri-implant tissue health of
      endosseous dental implants.
AB  - This study investigated the association of patient and provider characteristics
      on dental implant performance and survival probabilities. The outcomes of
      interest in this study were implant failures and peri-implant tissue health
      status. Univariate and bivariate statistics were used to describe the study
      population and to assess association of outcomes with patient and facility
      characteristics. Data were gathered from the period 1985 through January 1, 1990,
      from the Department of Veterans Affairs Dental Implant Registry. Logistic
      regression models were used to relate the outcomes with independent variables.
      Results showed that implant survival is associated with (1) the medical status of
      the patient, (2) the surface coating material of the implant, and (3) implant
      surgical and healing complications. Peri-implant soft tissue health was
      associated with (1) patient's use of tobacco, (2) surface coating of implants,
      and (3) implant provider's experience.

PMID- 8150520
TI  - Infections associated with prosthetic devices: clinical considerations.
AB  - The successful development of synthetic materials and introduction of artificial
      devices into nearly all body systems has been shadowed by the adaptation of
      microorganisms to the opportunities these devices afford for eluding defenses and
      invading the host. Clinicians are faced with the task of recognizing the
      manifestations of device-associated infection, predicting the likely pathogens
      involved, knowing the appropriate diagnostic methods, and initiating appropriate
      therapy. Infections associated with prosthetic heart valves are particularly
      challenging to successfully treat; surgical replacement may be necessary.
      Infection associated with an artificial joint usually requires removal of the
      device in addition to appropriate antibiotics. Intravascular associated
      infections are the leading cause of nosocomial bacteremias and, because of their
      intravascular location, these infections are often life catheter threatening if
      not promptly diagnosed and treated. Even contact lenses, external to epithelial
      surfaces, may give rise to serious sight-threatening infections. Although
      artificial devices play a paramount role in medicine today, infection is an ever
      present potential with which clinicians must be familiar.

PMID- 8150521
TI  - Cell biology and molecular mechanisms in artificial device infections.
AB  - Biomaterials are being used with increasing frequency for tissue substitution.
      Complex devices such as total joint replacement and the total artificial heart
      represent combinations of polymers and metal alloys for system and organ
      replacement. The major barrier to the extended use of these devices is bacterial
      adhesion to biomaterials, which causes biomaterial-centered infection, and the
      lack of successful tissue integration or compatibility with biomaterial surfaces.
      Adhesion-mediated infections are extremely resistant to antibiotics and host
      defenses and frequently persist until the biomaterial or foreign body is removed.
      The pathogenesis of adhesive infections is related, in part, to preferential
      colonization of "inert" substrate whose surfaces are not integrated with healthy
      tissues composed of living cells and intact extracellular polymers. Tissue
      integration is an interesting parallel to microbial adhesion and is a desired
      phenomenon for the biocompatibility of certain implants and biomaterials. Tissue
      integration requires a form of eukaryocytic adhesion or compatibility with
      possible chemical integration to an implant surface. Many of the fundamental
      principles of interfacial science apply to both microbial adhesion and to tissue
      integration and are general to and independent of the substratum materials
      involved. Interactions of biomaterials with bacteria and tissue cells are
      directed not only by specific receptors and outer membrane molecules on the cell
      surface, but also by the atomic geometry and electronic state of the biomaterial
      surface. An understanding of these mechanisms is important to all fields of
      medicine and is derived from and relevant to studies in microbiology,
      biochemistry, and physics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150522
TI  - Practical measures to control device-related bacterial infections.
AB  - Direct examination of medical devices that have been foci of chronic device
      related bacterial infections has shown that the causative organisms grow
      predominantly in slime-enclosed biofilms. These adherent biofilms are inherently
      resistant to host defences (antibodies, phagocytes) and to conventional
      antibiotic therapy. Device-related infections can be prevented by careful
      cleaning and sterilization of the device, and by the avoidance of any
      manipulations that would allow the formation of even the most rudimentary biofilm
      prior to implantation. Once a device-related infection has become established,
      both the Minimum Inhibitory Concentration (MIC) and the Biofilm Eliminating
      Concentration (BEC) of the causative organism must be determined and therapeutic
      strategy must aim at the use of the MIC to control the acute phase caused by
      planktonic bacteria and of the BEC to eliminate the biofilm nidus of infection.
      The removal of the colonized device should be considered early in the course of
      treatment if the BEC cannot be delivered to the colonized device. We describe a
      new bioelectric technology presently in the in vitro stage of development which,
      if it can be reproduced in vivo, will be very effective in the prevention and
      control of device-related bacterial infections.

PMID- 8150523
TI  - Infections associated with implanted blood pumps.
AB  - A variety of prosthetic blood pumps are currently undergoing experimental
      development or are available for clinical use. The Jarvik-7 and Jarvik 7-70
      (Symbion-7 and Symbion 7-70) total artificial hearts (TAH) have been used
      worldwide both experimentally and for clinical mechanical circulatory support. Of
      the 190 patients implanted with these devices, 133 went on to cardiac
      transplantation and 68 of the transplanted patients are alive. Complications
      associated with the use of the TAH have included postoperative hemorrhage,
      thrombosis with thromboembolism and infection. The incidence of infection in the
      patients implanted with the TAH has declined-significantly since initial clinical
      use and is now near 30%. Staphylococcus epidermidis and Pseudomonas aeruginosa
      are the most commonly pathogens isolated from these devices.

PMID- 8150524
TI  - An assay of Staphylococcus epidermidis biofilm responses to therapeutic agents.
AB  - Implant-associated infections tend to become persistent, resisting host defences
      and antibiotic therapy. Routine clinical laboratory testing of bacterial isolates
      in the fluid phase for antibiotic susceptibility may not be predictive of
      therapeutic outcomes and therefore a number of antibiotic regimes have been
      formulated empirically. The resistance of implant-associated infections has been
      ascribed to the production by bacteria, when adherent to the implant surface, of
      a shielding matrix of polymerized carbohydrates protecting the enclosed bacteria
      from immune defences and antibiotics. This complex of surface, bacteria and
      matrix is termed a biofilm. We describe a technique to evaluate the efficacy of
      antimicrobial agents directed against biofilm-forming strains of Staphylococcus
      epidermidis (a major cause of implant infections) utilizing standardized biofilm
      preparations formed on glass. The impact of the antimicrobial agents was assessed
      quantally using the end-point of permanent cessation of metabolic activity (cell
      death) of the entire biofilm determined by the loss of ability to reduce 2,3,5
      triphenyltetrazolium chloride to a visible red intracellular precipitate of
      formazan. The relative rate of action of differing antimicrobial agents could be
      determined by the minimum period of exposure of the biofilm to the agents that is
      required to bring about sterilization, the clinically relevant marker. A wide
      range of antimicrobial substances could be evaluated, including chemical
      disinfectants, immunoreactive substances, antibiotics; singly and in combination;
      and the modifying effects of interaction with non-antibacterial therapeutic
      agents and other environmental factors. The technique is simple, inexpensive,
      reproducible and readily adaptable to the clinical situation where evaluation of
      therapeutic regimes for individual cases of prosthetic device-associated
      infection is required routinely with despatch and ease of interpretation.

PMID- 8150525
TI  - A mouse model of implant-associated infection.
AB  - Infections of implanted devices are of increasing frequency and importance,
      representing a significant limitation of many therapeutic modalities. There are
      puzzling features of implant-associated infection including the changes in
      microbial flora, the tendency to chronicity and impaired responses to
      conservative modes of treatment. The concept of the bacterial biofilm as a
      shielding mechanism generated by bacteria adherent to artificial surfaces has
      recently been proposed as an explanation for these features. The biofilm is a
      term applied to a complex comprising the implant surface, adherent bacteria and a
      specialized matrix enclosing the bacteria. The matrix of the biofilm is an
      electrostatically charged glue-like extracellular polymer derived by bacterial
      enzymes acting on tissue carbohydrates, formed by bacteria when adherent to
      surfaces. This matrix binds the bacteria to the surface providing a sequestration
      affording selective protection against harmful elements of the environment,
      especially mechanisms of host defenses and antimicrobial agents. These biological
      systems are complex to study because of the dynamic interaction of the microbial
      variables, host defenses, properties of synthetic materials and the biofilm
      matrix itself. There is a need for a laboratory model in which the variables can
      be controlled permitting the researcher to examine the outcomes of modifying one
      variable at a time in a planned and orderly manner. The practical way to attain
      this end is the conduct of studies in a stable reproducible animal model of
      localized biofilm-implant infection. Staphylococcus epidermidis is a
      representative of the class of microorganisms predominant in implant-associated
      infection. This paper describes the development of a model utilizing an implant
      S. epidermidis-biofilm infection localized to the peritoneal cavity of the mouse.
      The natural history of the infection has been well documented and is stable in
      all respects for periods exceeding 3 months. This chronicity is especially
      advantageous in analyzing the impact of long-term therapeutic modalities and
      necessary periods of recovery and assessment. A representative example of an
      experimental use of this model to determine the relative efficacy of antibiotic
      therapeutic regimes is described, demonstrating its scope and efficacy.

PMID- 8150526
TI  - Multifactorial analysis of p53 alteration in human cancer: a review.

PMID- 8150527
TI  - Clinical outcome of colorectal cancer patients treated with human monoclonal anti
      idiotypic antibody.
AB  - A human monoclonal anti-idiotypic antibody (105AD7) has been developed which
      mimics a colorectal-tumour-associated antigen and induces cellular anti
      colorectal tumour immune responses in animals. Thirteen patients with advanced
      colorectal cancer were immunized with 105AD7 and their survival was compared with
      that of a contemporary group of unimmunized patients with similar disease status.
      No toxicity related to anti-idiotype immunization was seen. Cellular responses to
      anti-idiotypic immunization were indicated by lymphocyte proliferation to gp72
      positive tumour cells, and production of interleukin-2; anti-tumour antibodies
      were not detected. Median survival following diagnosis of advanced disease of
      immunized patients was 12 months, compared with 4 months in unimmunized patients.
      The improved survival of immunized patients in this study without associated
      toxicity suggests that 105AD7 immunization may have considerable potential for
      immunotherapy of colorectal cancer.

PMID- 8150528
TI  - Ouabain-resistant non-small-cell lung-cancer cell line shows collateral
      sensitivity to cis-diamminedichloroplatinum(II) (CDDP).
AB  - We have reported that the cellular uptake of cis-diamminedichloroplatinum(II)
      (CDDP) was inhibited by an Na+,K(+)-adenosine triphosphatase (ATPase) inhibitor,
      ouabain, in a human non-small-cell lung-cancer cell line, PC-14, but not in its
      CDDP-resistant cell line, PC-14/CDDP. [3H]Ouabain binding of PC-14/CDDP was about
      50% lower than that of PC-14. Accordingly, we speculated that a decrease in
      Na+,K(+)-ATPase activity in PC-14/CDDP might contribute to the decrease in
      cellular CDDP accumulation. To clarify the relationship between the activity or
      expression of Na+,K(+)-ATPase and cellular CDDP accumulation, we established an
      ouabain-resistant non-small-cell lung-cancer cell line (PC-14/OB300), which
      showed 1.9-fold resistance to the cytotoxicity of ouabain. Interestingly, this
      cell line was 4.2-fold more sensitive to CDDP than PC-14. The accumulation of
      CDDP in PC-14/OB300 was increased to 2.7-fold that in PC-14. This elevation of
      CDDP accumulation was not considered to be caused by increased passive diffusion,
      because the accumulation of CDDP in PC-14/OB300 was also inhibited by ouabain
      compared to PC-14. As one of the indices of Na+,K(+)-ATPase activity, we
      determined cellular 86Rb+ influx rates. The 86Rb+ influx rate was 1.5-fold higher
      in PC-14/OB300 and fell to 0.7-fold in PC-14/CDDP compared with PC-14. The mRNA
      expression of Na+,K(+)-ATPase was increased in PC-14/OB300 and decreased in PC
      14/CDDP. There was no difference in cellular [3H]ouabain binding between PC
      14/OB300 and PC-14. It is possible that Na+,K(+)-ATPase of PC-14/OB300 has a
      different affinity for ouabain from that of PC-14. Our results suggest that the
      enzyme activity or the level of expression of Na+,K(+)-ATPase may contribute to
      the cellular uptake of CDDP and determine the sensitivity to CDDP.

PMID- 8150529
TI  - Androgen responsiveness of the new human endometrial cancer cell line MFE-296.
AB  - MFE-296 endometrial cancer cells express androgen receptors in vitro. These
      cells, which are tumorigenic in nude mice, are derived from a moderately
      differentiated human endometrial adenocarcinoma. They express vimentin and the
      cytokeratins 7, 8, 18, and 19. Karyotyping revealed near-tetraploidy for most of
      the cells. No marker chromosomes were observed. DNA analyses confirmed the
      genetic identity of the cell line and the patient from whom the cell line was
      derived. Proliferation of MFE-296 cells was inhibited by the progestin R5020 and
      the androgen dihydrotestosterone (DHT). The inhibition of proliferation by DHT
      was antagonized by the antiandrogen Casodex, demonstrating the involvement of the
      androgen receptor. Androgen binding was determined at 22,000 binding sites per
      cell using a whole-cell assay (KD = 0.05 nM) and 30 fmol/mg protein with the
      dextran charcoal method; 7 fmol/mg protein of progesterone receptors were found,
      whereas estrogen receptors were below 5 fmol/mg protein. The androgen receptor
      was functionally intact, as demonstrated by transfection experiments with a
      reporter-gene construct, containing an androgen-responsive element. In MFE-296
      cells the content of the androgen receptor was up-regulated by its own ligand.

PMID- 8150530
TI  - DNA base modifications in renal chromatin of Wistar rats treated with a renal
      carcinogen, ferric nitrilotriacetate.
AB  - Ferric nitrilotriacetate (Fe-NTA) causes renal proximal tubular necrosis, a
      consequence of iron ion-mediated free-radical-associated damage, that finally
      leads to a high incidence of renal adenocarcinoma in male rats and mice. We have
      investigated the levels of typical hydroxyl radical-induced DNA base
      modifications in renal chromatin of male Wistar rats treated with a single or
      repeated administrations of Fe-NTA. Five pyrimidine-derived and 5 purine-derived
      modified DNA bases were identified and quantified by gas chromatography/mass
      spectrometry with selected-ion monitoring. The modified bases were 5-hydroxy-5
      methylhydantoin, 5-(hydroxymethyl)uracil, 5-hydroxycytosine, thymine glycol, 5,6
      dihydroxyuracil, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, xanthine, 2
      hydroxyadenine and 8-hydroxyguanine. The amounts of most of these compounds were
      significantly increased over control levels in renal chromatin of Fe-NTA-treated
      rats as measured 3 and 24 hr after treatment. Elevated levels of modified bases
      were accompanied by proximal tubular necrosis. On the 19th day, however,
      accumulation of modified DNA bases was not observed. Morphologically, scattered
      karyomegalic cells were seen in the proximal tubules, but necrosis was rarely
      found. Some of the identified DNA base lesions are known to be promutagenic,
      although others have not been investigated. Presence of modified DNA bases
      concomitant with necrosis and regeneration of the renal proximal tubules may be a
      critical step in Fe-NTA-induced carcinogenesis.

PMID- 8150531
TI  - Relaxin influences growth, differentiation and cell-cell adhesion of human breast
      cancer cells in culture.
AB  - The effects of different concentrations of relaxin (RLX) on growth and
      differentiation of a human breast-cancer cell line (MCF-7) have been studied
      after various times of exposure. The cells were cultured for 4 and 7 days in the
      absence (control) and the presence of highly purified porcine RLX at
      concentrations of 10(-9) M and 10(-6) M. (3H)-Thymidine uptake assay was used to
      evaluate cell proliferation. Electron microscopy and immunocytochemistry for the
      cell-cell adhesion molecule E-cadherin were carried out to evaluate cell
      differentiation. Analysis of DNA changes associated with apoptosis was performed
      to clarify whether RLX induces active cell death in the MCF-7 cells. The findings
      obtained show that RLX, when applied at micromolar concentrations, or even at
      nanomolar concentrations for long exposure times, suppresses proliferation,
      stimulates differentiation, and enhances expression of the surface molecule E
      cadherin. Growth inhibition is not accompanied by apoptosis. The results of this
      study show that RLX can be recognized as a novel agent active in influencing
      growth and differentiation of MCF-7 breast-cancer cells. When applied at
      appropriate concentrations and exposure times, the peptide has a growth
      inhibitory action, thus reversing the growth-stimulatory effect exerted at low
      concentrations for short exposure times, and promotes differentiation and cell
      cell adhesion. These last-mentioned properties might result in a decrease in
      invasiveness of breast adenocarcinoma cells.

PMID- 8150532
TI  - Estrogen replacement therapy and ovarian cancer risk.

PMID- 8150533
TI  - HPV 18 in cervical specimens from the Cook Islands.

PMID- 8150534
TI  - Preferential usage of T-cell receptor alpha beta variable regions among tumor
      infiltrating lymphocytes in primary human malignant melanomas.

PMID- 8150535
TI  - Invasion depth is the most important prognostic factor for transitional-cell
      carcinoma in a prospective trial of radical cystectomy and adjuvant chemotherapy.
AB  - The aim of this prospective study was to examine the prognostic
      pathomorphological factors in urothelial cancer of the urinary bladder. Clinical
      and morphological variables were evaluated by univariate and multivariate
      analysis in 70 patients with invasive transitional-cell carcinoma of the bladder
      (pTI-pT4a). The patients were treated according to a prospective program
      consisting of radical cystectomy and pelvic-node dissection, either alone or
      followed by adjuvant cisplatinum chemotherapy. Nodal status was pN0 in 89% of the
      patients. The median follow-up time was 5.75 years and the 5-year survival was
      58%. Among the morphologic variables, deep invasion of the bladder wall and
      squamous differentiation indicated a poorer prognosis. Differentiation grade,
      pattern of growth (infiltrating versus expanding), angioinvasive growth,
      glandular differentiation and concomitant prostate carcinoma (pT1) were not
      significative factors for survival. By contrast, a significant reduction in
      mortality rate was found in patients with concomitant carcinoma in situ.
      Multivariate analysis confirmed that depth of invasion is an independent
      prognostic factor of outcome. The results confirm the primary importance of tumor
      stage in the prediction of survival after radical cystectomy.

PMID- 8150536
TI  - Aberrations of tumor-suppressor genes (p53, apc, mcc and Rb) in esophageal
      squamous-cell carcinoma.
AB  - Loss of heterozygosity at 4 tumor-suppressor gene loci (p53, apc, mcc and Rb) was
      investigated using polymerase chain reactions, in 49 esophageal squamous-cell
      carcinoma specimens from patients who had undergone curative resection. Mutations
      in the p53 gene within exons 5 to 8 were also examined. LOH was detected in 9
      (43%) of 21 p53 genes, 16 (55%) of 29 apc genes, 10 (48%) of 21 mcc genes, and 13
      (52%) of 25 Rb genes for which heterozygosity could be determined. Mutations in
      the p53 gene were detected in 18 (36%) of 49 cases and were significantly more
      frequent in stage-III tumors and in tumors exhibiting DNA aneuploidy. In 5 cases
      where heterozygosity could be determined for all the loci, all had 2 or more
      aberrations. Additionally, a heterozygous deletion of p53 gene was associated
      with a mutation of the remaining allele in 8 (89%) of 9 cases. Short-term relapse
      within 3 to 12 months occurred significantly more frequently in patients having
      tumors with both p53 aberrations (p < 0.05). Thus, aberration of tumor-suppressor
      genes was a frequent occurrence in esophageal squamous-cell carcinoma and
      inactivation of the p53 gene may contribute to the progression of this tumor.

PMID- 8150537
TI  - Tobacco, alcohol and the risk of gastric cancer. A population-based case-control
      study in Sweden.
AB  - Previous studies have provided conflicting information on the role of tobacco and
      alcohol in gastric carcinogenesis. A population-based case-control study with 338
      histologically confirmed gastric-cancer cases and 679 control subjects was
      conducted. Information relating to life-time tobacco consumption, alcohol intake
      and diet during adolescence and 20 years before interview, and to socio-economic
      conditions was obtained through face-to-face interviews. Current cigarette
      smokers were found to have a greater risk than non-users of tobacco. The duration
      of cigarette or pipe smoking was positively associated with gastric-cancer risk.
      There was significant interaction between tobacco use and fruit consumption. High
      fruit intake was more protective among users of tobacco than among non-users, and
      the risk estimates associated with cigarette smoking were higher among those with
      low fruit consumption than among frequent fruit-eaters. Likewise, though to a
      lesser extent, vegetable intake interacted with tobacco use. Snuff dipping and
      alcohol intake was not associated with gastric-cancer risk. However, high alcohol
      intake tended to increase the risk associated with tobacco use. This study adds
      further support to the role of tobacco smoking in gastric carcinogenesis, and
      demonstrates that high intake of fruits and vegetables may be particularly
      beneficial in smokers.

PMID- 8150538
TI  - Early-life risk indicators of gastric cancer. A population-based case-control
      study in Sweden.
AB  - Exposures early in life seem to play an important role in the development of
      gastric cancer, but their nature is not well understood. In a population-based
      case-control study, we examined weight, height and body-mass index (BMI) at the
      age of 20 as well as indices of socioeconomic conditions. Face-to-face interviews
      were conducted with 338 of 456 eligible histologically confirmed gastric cancer
      patients and 679 of 880 eligible control subjects, sampled from population
      registers and frequency matched by age and gender. Gastric cancer risk was
      negatively associated with height. Risk was positively, associated with weight at
      age 20 in both sexes. The highest BMI-quartile was associated with an increased
      risk. This association between BMI and risk was confined to BMI at age 20, and
      disappeared for BMI 20 years prior to interview. High socioeconomic status (SES)
      as well as long education carried a decreased risk of gastric cancer. Number of
      siblings was positively associated with risk. Factors related to short stature
      and high adolescent body weight are associated with an increased risk of gastric
      cancer, as is a high number of siblings. These factors may reflect influences of
      dietary patterns early in life.

PMID- 8150539
TI  - Risk factors for oesophageal cancer in northeast China.
AB  - A hospital-based case-control study of oesophageal cancer was carried out in the
      Heilongjiang Province, a low-risk area for oesophageal cancer in China. From May
      1985 to May 1989, 196 histologically confirmed cases and 392 controls with other
      (non-neoplastic) diseases were personally interviewed in the wards of 5 major
      hospitals. Information was obtained about usual consumption in the early 1980s of
      32 major contributors to the diet in the province, socio-demographic status,
      smoking and alcohol consumption. Odds ratios (OR) were obtained from logistic
      regression models, and confounding was controlled by means of multivariate
      models. Smoking and alcohol consumption were major risk factors for oesophageal
      cancer in this population. Smokers of handmade cigarettes exhibited a
      particularly high risk. A near multiplicative synergism was found between smoking
      and alcohol consumption. There was a significant inverse dose-risk trend for
      combined consumption of vegetables and fruits; a 300-g increase per day lowered
      risk by 35%. Vitamin C intake was negatively associated with risk; a 100-mg
      increase per day lowered risk by 39%. Our data suggest a modifying effect of
      vitamin C and beta-carotene on risk associated with smoking, but the power of
      analyses was low. Salt, salt-preserved foods and pickled vegetables were not
      associated with increased risk. High temperature of meals and drinks was a strong
      risk indicator in this population. The strength of tea and overall tea
      consumption were independent determinants of the risk.

PMID- 8150540
TI  - Association of IgA-anti-Fab autoantibodies with disease stage in head-and-neck
      cancer.
AB  - Patients with head-and-neck cancer commonly have immune defects. It was reported
      that these patients have raised serum IgA levels. We investigated whether IgA
      anti-Fab autoantibodies, which occur in association with immune dysfunction, are
      present in patients with head-and-neck cancer. Sera of 101 patients with squamous
      cell carcinoma (SCCHN) and 8 patients with adenoid cystic carcinoma (ACCHN) of
      the head and neck were tested in ELISA for IgA-anti-Fab autoantibody activity.
      IgA-anti-Fab serum activity was significantly higher in both SCCHN and ACCHN
      patients than in healthy controls. In patients with SCCHN, an association between
      disease stage and IgA-anti-Fab activity was established. Stage-IV patients had
      significantly higher IgA-anti-Fab than stage-I patients or healthy controls.
      Stage-II and stage-III patients had intermediate levels. Extremely high IgA-anti
      Fab activity was observed in 7 patients who died within 6 months following
      testing, suggesting a relationship of autoimmunity with terminal disintegration
      of physiological body functions. IgA-anti-Fab autoantibodies may explain the
      occurrence of immune defects in patients with head-and-neck cancer.

PMID- 8150541
TI  - Non-involvement of ras mutations in flat colorectal adenomas and carcinomas.
AB  - Ras gene mutations occur relatively early during colorectal tumor development and
      have been observed in 40-50% of malignant colorectal tumors. Advances in
      endoscopic techniques have made it possible to detect small, flat colorectal
      tumors that could not be detected by standard examinations. To determine whether
      ras gene mutations are also involved in the genesis of small, flat colorectal
      tumors, we examined ras point mutations in 34 cases of small polypoid or flat
      elevated colorectal tumors (32 adenomas, 2 carcinomas) and in 26 cases of small,
      flat colorectal tumors (13 adenomas, 13 carcinomas) by means of the polymerase
      chain reaction (PCR) and dot-blot hybridization. Ras gene point mutations were
      observed in 16 of the 34 tumors of the former type (47%), but in none of the 26
      tumors of the latter type, even though the grade of dysplasia was severe in the
      flat tumors. Our results suggest that different genetic pathways for tumor
      progression may exist for polypoid and for flat colorectal carcinomas.

PMID- 8150542
TI  - Relationship between loss of estrogen and progesterone receptor expression and of
      6q and 11q chromosome arms in breast cancer.
AB  - The expression of estrogen (ER) and progesterone (PR) receptors was quantified in
      a series of 95 cytogenetically characterized breast cancers. The relationship
      between deficiencies of 6q and 11q arms (where genes for ER and PR are mapped,
      respectively) and ER and PR expression was analyzed. The range of variations in
      expression was very large by comparison to that of the number of chromosome arms.
      Furthermore, low expression without chromosome loss and high expression with
      chromosome loss were occasionally observed. Thus, major variations in ER and PR
      expression were independent of the number of copies of the corresponding gene.
      However, both the decrease in ER expression and 6q arm losses were correlated
      with cytogenetic evolution of the tumors, this correlation being less significant
      for PR and the 11q arm. In addition, 6q- but not 11q- tumors have, on the
      average, a low ER/PR ratio, whereas 11q- but not 6q- tumors have a low PR/ER
      ratio. When all 6q- or 11q- tumors were compared to those with no 6q or 11q
      losses, the average ER or PR value of the former was about half of the later.
      These data suggest that, in addition to a regulatory change of non-genetic
      origin, gene dosage effect plays a secondary, but significant, additional role.

PMID- 8150543
TI  - Production and tumour-binding characterization of a chimeric anti-CEA Fab
      expressed in Escherichia coli.
AB  - A recombinant chimeric Fab (rcFab), with Fv derived from the monoclonal A5B7
      antibody to carcinoembryonic antigen (CEA), and with human CHI and C kappa was
      cloned into pUC 19 and expressed in Escherichia coli. rcFab (10 to 12 mg per
      litre) was produced in bacterial culture fluid, and functional purified rcFab was
      isolated by affinity chromatography (using antibody to human C kappa) and size
      exclusion gel filtration. The rcFab did not show reduced affinity for CEA, and
      reacted with human colorectal tumours showing a typical anti-CEA pattern by
      immunocytochemistry; it was also stable after iodination. Biodistribution studies
      in nude mice bearing human tumour xenografts showed no toxicity and good tumour
      localization. Therapeutic ratios at early time points were better than those
      obtained with whole murine antibody. The results demonstrate that bacterially
      produced anti-CEA Fab is of use for tumour targeting.

PMID- 8150544
TI  - Differential induction of the two early genes c-jun and c-fos in weakly and
      strongly metastatic murine lymphoma cell lines.
AB  - Induction of the 2 early-response genes c-jun and c-fos was investigated in the
      weakly metastatic T-lymphoma Eb line and the related strongly metastatic
      lymphomacrophage ESb line to find possible correlations with their different in
      vitro and in vivo phenotypes. The response of c-jun was elicited by the protein
      kinase-C activators TPA and A23187 in ESb but not in Eb cells. A much lower
      response of c-fos was also found in Eb than in ESb cells, in this case by means
      of serum and the cAMP elevator forskolin. However, both TPA and the calcium
      ionophore A23187 were similarly effective in inducing fos-mRNA in both cell
      lines. The uncoupling of c-jun and c-fos induction in Eb, but not in ESb cells,
      as well as the uncoupling of c-fos response to different stimulators, point to a
      differential activation of these 2 early-response genes by the main signal
      transduction pathways in the 2 cell types. The coordinate/uncoordinate
      availability of the fos/jun heterodimer may confer distinct regulatory patterns
      on different target genes in ESb/Eb cells. Activation of these genes may underlie
      the distinct differentiation phenotypes and in vivo behavior of Eb/ESb cells.

PMID- 8150545
TI  - Molecular cloning and expression of a cDNA encoding a protein detected by the K1
      antibody from an ovarian carcinoma (OVCAR-3) cell line.
AB  - MAb KI recognizes a cell-surface glycoprotein (MW approximately 40 kDa) present
      in ovarian carcinomas, malignant mesotheliomas, squamous-cell carcinomas and
      normal mesothelial cells. In this study, expression screening was used to isolate
      cDNA clones encoding an antigen recognized by MAb KI from a cDNA library made
      from a human ovarian carcinoma cell line (OVCAR-3). Subsequently, other clones
      were isolated by DNA hybridization using a cDNA probe derived from one of the
      initial clones. The sequence of all the clones was similar. The longest cDNA
      contains 2,444 base pairs, and encodes a polypeptide of 263 amino acids with a
      calculated molecular weight of 30,511 daltons. The nucleotide sequence and
      deduced amino-acid sequence of the protein show no homology to other sequences in
      current data bases. In vitro translation of RNA transcripts from the cDNA inserts
      yielded polypeptides of 29 and 30 kDa. Similar-sized proteins were obtained upon
      expression of the cDNA in Escherichia coli, and these proteins were reactive with
      MAb KI. The protein(s) expressed in E. coli were purified and used to make rabbit
      or mouse antisera. These antisera reacted strongly with a soluble cytosolic
      protein in OVCAR-3 cells, but not with the membrane-bound antigen. Soluble
      cytosolic proteins of a similar size, recognized with MAb KI, were found in OVCAR
      3 and N87 (gastric cancer) cells but not in 10 other cancer cell lines. These
      data indicate that the cloned cDNA encodes a cytosolic protein that reacted with
      MAb KI. This soluble protein is expressed only in cells containing the CAKI
      surface glycoprotein, suggesting that the 2 proteins could be structurally
      related.

PMID- 8150546
TI  - Long-term open evaluation of amlodipine vs hydrochlorothiazide in patients with
      essential hypertension.
AB  - The long-term efficacy and safety of amlodipine (2.5 to 10 mg) once daily was
      compared with that of hydrochlorothiazide (HCTZ) (25 to 100 mg) daily in 139
      patients with mild-to-moderate hypertension. The study was a randomized, open
      label, parallel comparison of 50 weeks' duration. Patients were randomized in a
      2:1 ratio (amlodipine n = 92: HCTZ n = 47). Atenolol was added at week 12 if
      monotherapy was inadequate. At week 12, the mean reductions for supine and
      standing systolic and diastolic blood pressure values with amlodipine were found
      to be -15.2/-12.3 mmHg and -14.0/-11.6 mmHg respectively, as compared to -15.5/
      11.1 mmHg and -16.1/-10.1 mmHg after treatment with HCTZ. The percentage of
      patients responding to treatment at week 12 was 74% on amlodipine and 70% on
      HCTZ. The addition of atenolol in those patients not adequately controlled on
      monotherapy produced additional mean reductions in supine and standing systolic
      and diastolic pressures in both the amlodipine-atenolol group and in the HCTZ
      atenolol group. The incidence of adverse effects was 47% with amlodipine and 26%
      with HCTZ at 12 weeks. Overall, six patients were discontinued because of side
      effects while receiving amlodipine monotherapy and one from the HCTZ monotherapy
      group; none were discontinued because of side effects on combination therapy.
      Laboratory test abnormalities were reported by 16% of amlodipine-treated patients
      compared with 63% of patients on HCTZ. The antihypertensive effects of amlodipine
      and hydrochlorothiazide appeared to be comparable and were maintained during long
      term therapy.

PMID- 8150547
TI  - Flecainide acetate: concentration-response relationships for antiarrhythmic and
      electrocardiographic effects.
AB  - In order to evaluate the concentration-response relationship for either
      antiarrhythmic or electrocardiographic effects, 13 patients with symptomatic,
      stable, premature ventricular contractions (> 100/hour) were selected, and
      flecainide was administered as a single oral dose (200 mg) and as chronic
      treatment (150 mg b.i.d. for 21 days). In both settings a Holter monitoring,
      serial electrocardiogram (ECG) tracings and serum samples for flecainide
      concentrations were obtained; the relationships between drug levels,
      antiarrhythmic efficacy, and ECG modifications were analysed. The results
      obtained indicated that QRS and PR intervals lengthened significantly either
      after acute oral administration or after chronic treatment by 21-36% (mean
      values), and that the QRS interval changes were significantly correlated to serum
      flecainide concentrations (r = 0.68, p < 0.001 after acute and r = 0.79, p <
      0.001 after chronic administration). However, for any given plasma concentration
      of flecainide, the percentage widening of QRS intervals was smaller after chronic
      treatment, as shown by the different slopes of the correlation lines (7.7 +/-
      4.0% ml.micrograms -1 after acute dosing versus 3.8 +/- 1.1% ml.micrograms -1
      after chronic treatment, p < 0.001). This finding suggests a relative reduction
      of flecainide's effects on ECG intervals during chronic treatment, while the
      antiarrhythmic efficacy was maintained (flecainide effective in 8/13 patients in
      acute and in 11/13 patients in chronic) without significant differences between
      flecainide's minimal effective concentrations (262 +/- 119 ng/ml and 319 +/- 276
      ng/ml for acute vs chronic respectively). We conclude that during chronic
      treatment a dissociation seems to occur between the electrocardiographic and the
      antiarrhythmic effects and this could limit the clinical usefulness of monitoring
      QRS intervals.

PMID- 8150548
TI  - Ideal therapeutic range of cyclosporine in whole blood in kidney-transplanted
      patients.
AB  - Two hundred and eighty-seven renal-transplanted recipients treated with
      cyclosporine were monitored for their cyclosporine trough blood level
      periodically. Based on the monitor results, we now can define the ideal
      therapeutic range of cyclosporine in whole blood as follows: 500-600 ng/ml in the
      first week of post-transplantation, 600-800 ng/ml in the second week to sixth
      month of post-transplantation, 400-600 ng/ml in the seventh to twelfth month of
      post-transplantation and 350-400 ng/ml 1 year after post-transplantation.

PMID- 8150550
TI  - Pharmacokinetics and pharmacodynamics of dermatan sulfate after intravenous and
      intramuscular administration to healthy volunteers.
AB  - The pharmacokinetics and pharmacodynamics of dermatan sulfate (DS) was
      investigated in healthy volunteers (two groups, namely group A: 6 subjects, group
      B: 8 subjects). The subjects of group A received 100 mg of DS both i.v. and i.m.
      and the subjects of group B received 400 mg of DS both i.v. and i.m. in two
      different days. The resulting anticoagulant activities were assessed by the
      activated partial thromboplastin time (aPTT) and the pharmacokinetic parameters
      were calculated from the plasma concentrations of DS measured by a chromogenic
      assay. The plasma concentrations of DS were fitted by linear and non-linear
      elimination models (i.e. assuming that the drug elimination follows Michaelis
      Menten kinetics). Some evidence of non-linear kinetics was given by the
      observation that the mean terminal half-life and clearance estimated by the
      linear model were not independent of the i.v. dose (0.83 +/- 0.1 and 1.74 +/-
      0.21 hours and 4.94 +/- 0.64 and 2.67 +/- 0.27 l/h after 100 and 400 mg i.v.
      respectively. Moreover the mean half-lives estimated after i.m. administrations
      were much higher than the values estimated after the i.v. dose (2.03 +/- 0.74 and
      3.54 +/- 1.3 hours after 100 and 400 mg) and linear models failed to fit
      simultaneously the DS plasma concentrations after both the administration routes.
      Using the linear model, the mean drug bioavailability after i.m. administration
      was estimated to be about 30% and 80% after the 100- and the 400-mg dose
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150549
TI  - Penetration of cefpirome into sputum in chronic respiratory infections:
      comparison of administration of 0.5 g and 1.0 g in the same patient.
AB  - This study evaluated the sputum penetration of cefpirome following slow
      intravenous infusion of 0.5 and 1.0 g using a comparative cross-over design to
      reduce variability. Five patients with chronic respiratory tract infections were
      randomized to receive either 0.5 g followed by 1.0 g, or by 1.0 g followed by 0.5
      g cefpirome, by slow intravenous infusion over 1 h, with a 24-h wash-out period
      between each treatment. With the exception of one patient, sputum concentration
      correlated well with plasma concentration. Higher sputum levels of cefpirome were
      achieved following the higher dose.

PMID- 8150551
TI  - The use of modulated energy carried on a high frequency wave for the relief of
      intractable pain.
AB  - Ten volunteer patients with chronic neck/shoulder or back pain had been taking
      analgesics, and using conventional transcutaneous electrical nerve stimulation
      (TENS) with no significant pain relief. On entry to the trial, they were
      requested to stop taking their analgesics for two days prior to the study and for
      two days after starting to use the Liss Bipolar Body Stimulator for 20 min 3-5
      times daily. Resumption of medication was then allowed. The stimulator (15,000 Hz
      carrier wave with a double modulation of 15 and 500 Hz) was connected to two
      adhesive electrodes placed so that the current field encompassed the trigger
      points, and used at a current that was just threshold for perception (1-4 mA). A
      visual analogue pain score was recorded before the study, and each evening of the
      month's study. The pain showed an overall highly significant rapid reduction of
      approximately 62% (p < 0.001), and all but two of the patients received
      substantial benefit throughout the study. We conclude that the Liss Bipolar Body
      Stimulator usually causes a substantial reduction of pain even in patients not
      helped by conventional TENS devices.

PMID- 8150552
TI  - Invisible antivirals.

PMID- 8150553
TI  - Effects of oral administration of Lactobacillus casei on antitumor responses
      induced by tumor resection in mice.
AB  - The effects of an oral administration of BLP, a preparation of viable
      Lactobacillus casei YIT 9018, upon tumor growth and the mitogenic responses of
      splenocytes from tumor-bearing mice were studied. BALB/c mice were insufficiently
      pre-immunized by resecting a Colon 26 tumor mass (primary tumor) grown for 5 days
      intradermally. Thereafter, mice were rechallenged by injecting Colon 26 tumor
      (secondary tumor) into the hind footpad. The secondary tumor grew progressively
      in control mice, but was markedly suppressed by oral administration with BLP at a
      dose of 100 or 200 mg/kg/day for 7 consecutive days. The suppression was a
      primary tumor-specific response. Viable L. casei, not heat-killed L. casei, could
      suppress the secondary tumor. Although the lymphoproliferative responses of
      splenocytes from the secondary tumor-bearing mice with T-cell mitogens
      (concanavalin A and phytohaemagglutinin) and cytokines (interleukin-1 and
      interleukin-2) were lower than those of normal mice, this suppression of
      mitogenic responses under tumor-bearing conditions was abolished by oral
      administration with BLP. Thus we concluded that oral BLP potentiated systemic
      immune responses that modified T-cell functions in tumor-bearing mice.

PMID- 8150554
TI  - Anti-CD6-blocked ricin: an anti-pan T-cell immunotoxin.
AB  - We report the development of a potent anti-pan T-cell immunotoxin capable of
      killing cells in an antigen dependent manner. The immunotoxin is composed of a
      high affinity anti-CD6 antibody (IgG2a, Kd = 1.3 x 10(-11) M) conjugated to
      blocked ricin that is a chemically modified ricin molecule wherein the lectin
      binding sites of the B-chain have been blocked by covalent attachment of affinity
      ligands. Conjugation of blocked ricin to the antibody has minimal effect on the
      apparent affinity of the antibody and no effect on the ribosome-inactivating
      activity of the ricin A-chain moiety. Anti-CD6-blocked ricin is a specific and
      highly toxic immunoconjugate killing the antigen-positive Molt-4 cell line with
      an IC37 of 4 x 10(-12) M after a 24 h exposure of cells to the immunotoxin.
      Nonspecific cytotoxicity of anti-CD6-blocked ricin for the antigen-negative
      Namalwa cell line was more than 750-fold lower with an IC37 > 3 x 10(-9) M. The
      cytotoxicity of anti-CD6-blocked ricin is dependent on the length of the
      incubation of cells with the conjugate ranging from an IC37 of 1.5 x 10(-11) M
      leaving a surviving fraction of Molt-4 cells of 0.03 after a 2.5 h exposure to an
      IC37 of 5 x 10(-13) M and leaving a surviving fraction of 3 x 10(-6) after a
      continuous (3 weeks) exposure. Anti-CD6-blocked ricin is also capable of killing
      CD6 positive cells in human peripheral blood lymphocyte populations. Systemic
      toxicity of anti-CD6-blocked ricin in mice is similar to the toxicity of other
      immunotoxins containing blocked ricin that were found to be tolerated well by
      patients. An application of this immunoconjugate for the prevention and treatment
      of graft versus host disease or tissue graft rejection is suggested.

PMID- 8150555
TI  - Microcytic anemia and changes in ferrokinetics as late after-effects of glucan
      administration in murine hepatitis virus-infected C57BL/10ScSnPh mice.
AB  - Mild microcytic anemia (without changes in mean corpuscular hemoglobin
      concentration, MCHC) was discovered 6-14 weeks after a single s.c. administration
      of 4 mg of particulate glucan to C57BL/10ScSnPh mice serologically positive for
      murine hepatitis (MHV). The anemia was associated with granulocytosis, decreased
      body weight and spleen hypertrophy. The overall intensity of erythropoiesis was
      measured by 59Fe-incorporation into the heme of erythropoietic organs. The
      localization of erythropoiesis became markedly redistributed--heme production was
      suppressed in the bone marrow while a several-fold increase was recorded for the
      spleen. A new steady state was also discovered in ferrokinetics: an iron pool
      localized away from the blood, erythropoietic organs and the liver was
      significantly elevated, and hypoferremia was detected. Anemia and wasting of mice
      were not observed in the same mouse strain free of MHV. A single administration
      of particulate glucan resulted in late impairment of red blood cell formation in
      the C57BL/10ScSnPh mouse strain infected with the mouse hepatitis virus. The
      anemia shares a number of features with those observed for the anemia of chronic
      diseases.

PMID- 8150556
TI  - Effect of lipoic acid on cyclophosphamide-induced diabetes and insulitis in non
      obese diabetic mice.
AB  - In an animal model of type I diabetes, the non-obese diabetic (NOD) mouse, the
      influence of the antioxidant lipoic acid (LA) on the development of diabetes was
      investigated. Acceleration of diabetes development with cyclophosphamide (CY)
      resulted in 60% diabetic animals with severely infiltrated islets within 1-3
      weeks. Daily administration of lipoic acid for 20 or 30 days around
      cyclophosphamide treatment suppressed the incidence of diabetes to 30% (P < 0.05)
      and 33%, respectively. Semiquantitative analysis of islet infiltration showed a
      reduction of severe intraislet infiltration and an increase in the percentage of
      islets with mild per-insular and periductular infiltrates (from 8.4 to 29.6 and
      25.9%, respectively, P < 0.01) after lipoic acid treatment. These results show
      that the protective effect of lipoic acid on diabetes development correlates with
      partial suppression of islet inflammation. The anti-inflammatory action of lipoic
      acid may be due to its ability to scavenge oxygen radicals and to suppress nitric
      oxide production.

PMID- 8150557
TI  - Augmentation of host defense mechanisms against tumor by sperabillin polymers,
      new basic peptidyl biopolymers, in mice.
AB  - Sperabillin polymers, which have been shown recently to have antitumor activity,
      are new basic peptidyl polymers composed of a pseudo-peptide antibiotic,
      sperabillin A. The polymers, HP-2 (MW 9990), AP-2 (MW 20,100) and AB-2 (MW
      35,000), were found to potently activate murine peritoneal macrophages. The
      phagocytosis-dependent respiratory burst and Fc gamma receptor expression of
      peritoneal macrophages from C57BL/6 mice were enhanced after in vitro cultivation
      with these polymers. When HP-2, a representative of these polymers, was
      intraperitoneally injected into mice, the number of peritoneal exudate cells
      increased and phagocytosis-dependent respiratory burst and class II (I-A) antigen
      expression of peritoneal macrophages were augmented. These macrophages showed
      strong inhibitory activity against the growth of murine tumor cell lines such as
      EL4 lymphoma and B16 melanoma. Nitrogen oxide, tumor necrosis factor (TNF) and
      interleukin 1 (IL-1) might be required for this inhibitory activity. Moreover, in
      mice treated with HP-2, splenocyte counts also increased and non-specific killer
      activity of the splenocytes was augmented. These results indicate that
      sperabillin polymers are new macrophage activators.

PMID- 8150558
TI  - Enhancement of polymorphonuclear leukocyte (PMN) function by OK-432.
AB  - The influence of OK-432, a streptococcal preparation, on human polymorphonuclear
      leukocytes (PMN) was examined. OK-432 increased O2- generation was also observed
      when PMN were cultured with 10(-2)KE/ml OK-432 for 1 h and then stimulated with
      phorbol myristate acetate or formyl-metionyl-leucil-phenylalanine (FMLP). In
      addition, PMN O2- generation was promoted by culture supernatants of peripheral
      blood mononuclear cells (PBMC) incubated with 10(-3) or 10(-2) KE/ml OK-432.
      Furthermore, OK-432 (10(-3)-10(-2) KE/ml) enhanced the chemiluminescence of FMLP-
      and PMA-stimulated PMN. However, nitroblue tetrazolium reduction and
      myeloperoxidase activity were only minimally enhanced. Not only the candidacidal
      activity of PMN but also antibody-dependent cell-mediated cytotoxicity against
      Candida and Raji cells were enhanced in correspondence with the increased
      generation of reactive oxygen species. Culture of PMN or PBMC for 24 h with OK
      432 resulted in a concentration-dependent increase in the substantial production
      of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha. OK-432 also
      enhanced granulocyte-macrophage colony stimulating factor and gamma-interferon
      generation by leukocytes in a dose-dependent manner. Our research indicates that
      OK-432 enhances PMN function directly as well as via the promotion of cytokine
      production, and suggests that these effects of OK-432 could be beneficial in
      immunosuppressed patients.

PMID- 8150559
TI  - Health care paper chase, 1993: the cost to the nation, the states, and the
      District of Columbia.
AB  - The U.S. health care payment system is an elaborate and increasingly wasteful
      paper chase. This article presents new state-by-state estimates of health care
      administrative costs in the United States, and savings that could be realized
      with single-payer reform. In 1993, health care bureaucracy will consume 24.7
      cents of every health care dollar, a total of $232.3 billion. Administration's
      share of health spending is up from 23.9 percent in 1987, and from 21.9 percent
      in 1983. Reducing the cost of administration to Canadian levels by adopting a
      single-payer health care system would cut U.S. health care bureaucracy by more
      than half (50.7 percent), saving at least $117.7 billion in 1993. The savings
      achievable with a single-payer system could fund universal access for the
      uninsured and improve benefits for the tens of millions of Americans who
      currently have only partial coverage, without any increase in overall health
      spending. Reform measures such as electronic billing, insurance industry
      consolidation, and increased competition (including "managed competition") would
      save little or nothing on administration. Only a single-payer reform that
      incorporates the "macro-management" approach to cost control, as in Canada, can
      achieve significant administrative savings.

PMID- 8150560
TI  - Labor union programs to reduce or prevent occupational stress in the United
      States.
AB  - In the United States, most efforts to reduce occupational stress continue to
      focus primarily on personal stress management. However, there has been a growing
      awareness that personal coping techniques have limited effectiveness and that
      sources of stress in the work environment need to be altered. Research on
      workplace sources of stress has been spurred and guided by Karasek's "job strain"
      or "job demands-control" model, and the University of Michigan model of the
      stress process. In addition, a model of occupational stress interventions
      developed by Karasek provides a useful framework for stress prevention
      activities. U.S. labor unions have undertaken a variety of activities at all
      stages of the stress process described by this stress intervention model to
      reduce or prevent the health hazards associated with occupational stress. These
      programs and strategies include employee assistance programs, educational
      programs, stress surveys, medical studies, stress committees, collective
      bargaining, organizing and public awareness, and lobbying and political action.
      These programs are described and analyzed in relation to models of occupational
      stress, as well as to the economic context faced by labor unions today, and
      continuing obstacles to work environment reform.

PMID- 8150561
TI  - Managed competition: an analysis of consumer concerns. The Working Group on
      Managed Competition.
AB  - Advocates for health care reform (representing a broad range of constituencies)
      raise serious concerns about the ability of managed competition to meet the
      health care needs of the American people. Similarities in managed competition
      proposals include establishment of a collective purchasing authority, creation of
      health plans, standardization of rules and requirements, and limitation on tax
      subsidies. Managed competition proposals vary as to whether they call for true
      universality, meaningful cost containment, and fair financing. The article raises
      questions about managed competition, including the technical feasibility; the
      link to employment; the role for insurance companies; severing the link between
      insurance and income, age, or health status; comprehensive benefits; cost
      containment; the role for managed care; universality of coverage; and the role
      for insurance companies to make treatment decisions.

PMID- 8150562
TI  - Asbestos hazard evaluation in South Korean textile production.
AB  - The manufacture and use of asbestos-containing products has become the object of
      restrictive environmental and occupational health regulation in the United States
      and many European countries. World production, however, has not declined, but
      rather shifted to developing countries. Our knowledge of the working conditions
      in these countries is limited. This article describes an investigation conducted
      in 1991 into the conditions and work practices in asbestos textile manufacturing
      in South Korea. The findings are based on site visits to several asbestos textile
      manufacturing facilities, meetings with industrial safety experts, and labor and
      industry representatives. The authors describe the current status of exposure
      control technology and industrial hygiene practices, and the results of personal
      asbestos dust monitoring at five representative textile production workstations.
      In general, manufacturers and regulatory agencies have not taken the precautions
      necessary to adequately protect employee health and meet international standards.
      Worker exposure to asbestos dust well above U.S. and German standards is
      commonplace in South Korea. International cooperation of health and safety
      experts with experience in asbestos-related problems should be promoted to
      improve the level of industrial safety in developing countries.

PMID- 8150563
TI  - Environmental and occupational pollutants are avoidable causes of breast cancer.
AB  - For over three decades, evidence has accumulated relating avoidable exposures to
      environmental and occupational carcinogens to the escalating incidence of breast
      cancer in the United States and other major industrialized nations. This evidence
      has until very recently been totally ignored by the cancer establishment, the
      National Cancer Institute, and the American Cancer Society, despite expenditures
      of over $1 billion on breast cancer research. Recognition of these environmental
      and occupational risk factors should lead to the belated development of public
      health policies directed to the primary prevention of breast cancer. Their
      recognition should also lend urgency to the need for radical reforms in the
      priorities and leadership of the cancer establishment.

PMID- 8150564
TI  - A simplistic approach to health policy analysis: the World Bank team on the
      Indian health sector.
AB  - A World Bank report on the health sector in India has set out to offer an
      alternative policy framework to cushion the impact of structural adjustment
      programs on health services. By choosing health financing as a tool for policy
      analysis, it has arrived at highly questionable conclusions.

PMID- 8150565
TI  - The politics of suffering: the impact of the U.S. embargo on the health of the
      Cuban people. Report of a fact-finding trip to Cuba, June 6-11, 1993.
AB  - The past several years have been difficult for the Cuban people. The economies of
      Cuba's major trading partners have collapsed. The 33-year U.S. embargo was
      tightened with passage of "The Cuban Democracy Act of 1992" to include trade-
      mostly in food and medicines--by subsidiaries of U.S. companies in other
      countries. The March 1993 "Storm of the Century," which devastated communities
      from the Caribbean to Canada, caused an estimated $1 billion in damage to Cuba. A
      mysterious disease known as neuropathy, which can affect vision, appeared in late
      1991 and has spread throughout the island. All this has created a situation of
      scarcity and uncertainty that has affected all aspects of Cuban society,
      including its health care system. In June 1993 a delegation that included members
      of the American Public Health Association traveled to Cuba to investigate the
      current health situation in the country, with an emphasis on the impact of the
      U.S. embargo. The delegation found that compared to two and three years ago, the
      general standard of living in Cuba and the quality of health services have
      declined dramatically. It concluded that while the overall health of the Cuban
      population has not yet seriously eroded as a result of the economic decline,
      severe problems threaten to emerge in the future. The delegation called for
      lifting of the embargo as part of a new approach in U.S. policy toward Cuba.

PMID- 8150566
TI  - Social class: the missing link in U.S. health data.
AB  - National vital statistics in the United States are unique among those of advanced
      capitalist countries in reporting data only by race, sex, and age--not by class
      and income. This article reviews the limited U.S. data resources that may be used
      to document social class inequalities in health. Summarizing the strengths and
      weaknesses of the British approach to gathering data on social class and health,
      the authors discuss possible approaches to collecting data that could be feasible
      in the U.S. context. They argue that educational level is an insufficient marker
      for socioeconomic position and contend that appropriate measures must take into
      account not only individual but also household and neighborhood markers of social
      class. These additional types of social class data are especially important for
      accurately describing and understanding social class inequalities in health among
      women and across diverse racial/ethnic groups.

PMID- 8150567
TI  - Change in the British National Health Service: policy paradox and the rationing
      issue.
AB  - The National Health Service of the United Kingdom is trapped in a policy paradox.
      On the one hand, the 1990 reforms encourage the devolution of power to local
      purchaser and provider units through the operation of the "internal market." On
      the other, mechanisms of control and accountability are being revamped to produce
      a centrally managed system bound together by corporate contracts. The political
      frictions generated by this paradox are exacerbated by the problem of rationing
      health care in the face of apparently unlimited demand. This article examines the
      political problems faced by a single Health Authority as it sought to implement
      the changes required of it by the conflicting policies.

PMID- 8150568
TI  - Femininity, responsibility, and the technological imperative: discourses on
      breast cancer in the Australian press.
AB  - The manner in which the popular press represents health issues influences, and is
      demonstrative of, societal attitudes toward illnesses and those who suffer from
      them. Cancer is one of the most feared diseases in modern society, and breast
      cancer attacks women at the bodily site where notions of femininity intersect.
      This article examines the discourses surrounding breast cancer as represented in
      the Australian press in the period between 1987 and 1990. It is argued that the
      press's portrayal of breast cancer during that time drew upon dominant cultural
      metaphors and discourses concerning femininity, the individual's responsibility
      for illness, and medical and technological dominance.

PMID- 8150569
TI  - Canadian marketing codes: how well are they controlling pharmaceutical promotion?
AB  - Pharmaceutical promotion in Canada is controlled by two codes: a voluntary one
      developed by the Pharmaceutical Advertising Advisory Board dealing mostly with
      printed promotional material, and one from the Pharmaceutical Manufacturers
      Association of Canada covering other forms of promotion. This article looks at
      enforcement of the provisions of these codes and at areas in which they are
      deficient. One of the major weaknesses in both codes is their lack of effective
      sanctions for companies that violate their provisions. Strong codes are necessary
      because many physicians rely heavily on promotional material for their source of
      prescribing information. However, voluntary codes or codes developed by the
      industry are inherently weak and lack effective enforcement mechanisms. Although
      the U.S. Food and Drug Administration is currently very active in curtailing
      promotional excesses, government control is not the solution since regulatory
      action will depend on the ideological position of the head of the regulatory body
      and/or the party in power. An independent body backed by legislative authority is
      preferable.

PMID- 8150570
TI  - The homeless mentally ill: myths and realities.
AB  - This literature review summarises the historical background of homelessness. It
      suggests that the current view of homeless people as chronic mentally ill is the
      latest phase in a series of the different ways in which society has perceived and
      labelled the homeless. We have argued that homelessness is a product of the lack
      of housing provision to the poorest section of society and that the psychiatric
      needs of many of the homeless might be a direct result of poverty and
      homelessness. This review also highlights difficulties in interpreting data
      produced by surveys of homeless people. These difficulties include the multiple
      definitions of homelessness used and also the major methodological errors which
      limit the usefulness of their findings. In particular sampling methods used may
      have overestimated the more visible part of the homeless population,
      overestimating the levels of psychiatric morbidity. Even if these limitations are
      ignored the data produced by these studies do not allow planning of effective
      mental health services for homeless people as their results depend mainly on
      diagnostic classification rather than disability or need. What is required is a
      study of needs where the appropriateness of particular services is defined, the
      sampling method is explicit and the definitions of homelessness are precise and
      consistent.

PMID- 8150572
TI  - The impact of unemployment on psychosomatic symptoms and mental well-being.
AB  - The relationship between psychosomatic symptoms and mental well-being among
      unemployed (N = 132) and employed (N = 187) personnel of two similar wood
      processing factories was studied. Mental well-being was measured by means of the
      12-item General Health Questionnaire (GHQ-score) and the 13-item Beck Depression
      Inventory (BDI-score). The 13-item questionnaire assessing psychosomatic symptoms
      was used (PS-score). The 33 and 66 percentiles (tertiles) were formed on the
      basis of PS-score of the two groups separately. The highest PS-score percentile
      was compared with the combined first and second percentile. Higher PS-score
      implied impaired mental well-being especially in the unemployed but also in the
      control group. Insufficient social support and uncertainty about the future was
      associated with highest PS-score in the study group but not in the control group.
      High PS-score was associated with subjective mental problems in both groups.
      Impaired health and PS-score were associated in both groups. Our results suggest
      that unemployment is a powerful external stress factor and that psychosomatic
      symptoms were associated with impaired mental well-being.

PMID- 8150571
TI  - Post-abortion perceptions: a comparison of self-identified distressed and
      nondistressed populations.
AB  - This study investigated the experiences of 25 women who described themselves as
      responding in an emotionally distressed manner to abortion and a comparison group
      of 25 women reporting more relieving/neutral responses. Current and initial
      stress response to the abortion, general mental health, and demographic
      characteristics were assessed quantitatively, and interviews explored subjective
      perceptions. The distress group had significantly higher scores on initial stress
      response and religiosity, were more often currently affiliated with conservative
      churches, and reported lower degree of social support and confidence in the
      abortion decision. Qualitatively, 48% of the distress group recalled experiencing
      feelings of loss immediately post-abortion, in contrast to none in the
      nondistress group. Both groups identified post-abortion "catalytic" events, such
      as subsequent childbirth, that affected responses to the abortion over time.

PMID- 8150573
TI  - The factor structure of the Turkish version of the General Health Questionnaire.
AB  - The 60-item General Health Questionnaire (GHQ) was translated into Turkish and
      administered to a community sample of 437 Turkish-speaking immigrants resident in
      Melbourne, Australia. The factor structures of the 60-item and 28-item versions
      of the GHQ were examined to determine the cross-cultural validity of the four
      subscales of the 28-item GHQ "anxiety/insomnia", "social dysfunction", "severe
      depression" and "somatic complaints". Four-factor principal components analyses
      yielded factors which corresponded to similar underlying traits, but the pattern
      of symptom loadings differed in several ways. Insomnia was less closely
      associated with anxiety, and general illness ratings such as "not feeling
      perfectly well" were not uniquely associated with somatic symptoms. The
      "anxiety/insomnia" and "severe depression" factors overlapped, with many symptoms
      partially correlated with both factors. These factors appeared to be due to
      variations in the frequency of occurrence of these symptoms rather than a
      qualitative distinction between anxiety and depression.

PMID- 8150574
TI  - Severely and persistently mentally ill patients in Italy: an overview of
      epidemiological and psychosocial findings.
AB  - The aim of this paper is to provide an overview of epidemiological, clinical and
      psychosocial characteristics of patients needing long-term treatment. The data
      concerned the following aspects: prevalence and incidence from the five best
      established Italian psychiatric case registers; needs for care; psychosocial and
      clinical outcome as assessed by means of follow-up studies; social disability and
      relatives' perceived burden. The one-year prevalence rate of "long-term users" is
      consistent in Northern Italy, higher in Middle Italy and lower in Southern Italy.
      The incidence rate was found to be around 4 per 100,000. Even in a community
      oriented mental health service, users' needs for care are only partially met. A
      good psychosocial outcome was found associated with the use of social and/or
      vocational skills training, while the average number of days per year of
      hospitalization in a psychiatric department was found associated with poor
      outcome. A moderate degree of social disability was found among patients needing
      long-term treatment. The resulting family burden presented to a marked or very
      marked degree in more than 50% of the relatives.

PMID- 8150575
TI  - Effects of occupational status on the mental health of young Italian men and
      women. A cross-sectional study.
AB  - The study was carried out on 548 subjects (307 women, 244 men) between the ages
      of 21 and 26, who had all obtained secondary school certificates. The survey was
      conducted in two contrasting areas, one showing a high rate of unemployment, the
      other a rate below the national average. The sample was divided into three groups
      according to occupational status: employed persons, students and persons seeking
      their first employment. The subjects were given five questionnaires: a
      demographic form, the General Health Questionnaire, the Beck Depression
      Inventory, the Beck Hopelessness Scale and the Rosenberg Self-Esteem Scale. Our
      findings revealed that unemployed women experience greater psychological distress
      while men are more subject to marked depressive states. There were no significant
      differences between the two areas surveyed.

PMID- 8150576
TI  - [Principles of genetic technology and molecular diagnosis].

PMID- 8150577
TI  - [Principles of gene therapy].

PMID- 8150578
TI  - [Molecular biology in hematology/oncology].

PMID- 8150579
TI  - [Molecular biology in clinical immunology].

PMID- 8150580
TI  - [Molecular biology in cardiology. Changes in the phenotype in heart failure and
      myocardial hypertrophy].

PMID- 8150581
TI  - [Molecular biology in hepatogastroenterology and infectiology].

PMID- 8150582
TI  - [Molecular biology in neurology].

PMID- 8150583
TI  - [Medical ethics aspects of gene technology].

PMID- 8150584
TI  - [Amebic liver abscess. The problem of diagnosing hepatic amebiasis after several
      years of incubation].

PMID- 8150585
TI  - [Aspergillus-induced exogenous allergic alveolitis in a rural gardener].

PMID- 8150586
TI  - [Comments on the contribution by B.-D. Gonska (drug therapy). Amiodarone].

PMID- 8150587
TI  - [Comments on the contribution by G. F. Hauf and H. Roskamm. Heart failure in
      coronary heart disease].

PMID- 8150588
TI  - [Roentgen findings in lung diseases].

PMID- 8150589
TI  - Heading in a new direction.
AB  - Health system reform may be down the road, but significant changes in the
      environment in which Iowa physicians practice are just around the corner. In the
      near future, the growth of managed care will have a profound effect on health
      care delivery. What are your options in this new environment?

PMID- 8150590
TI  - Low back pain resolution.

PMID- 8150591
TI  - Trisomy 22 in an Iowa newborn.

PMID- 8150592
TI  - Sequence and sequence analysis of E1 and pIX regions of the BAV3 genome.
AB  - Bovine adenovirus type 3 (BAV3) is a DNA virus that causes respiratory and
      gastrointestinal disorders in cattle. We have sequenced the extreme left end of
      BAV3 genome (0-11.7 map units). Partial analysis of the nucleotide sequence
      revealed 19 potential open reading frames (ORFs) that could encode for
      polypeptides of 50 or more amino acids. Four of these ORFs show homology to known
      adenovirus polypeptides. The four BAV3 ORFs are located in approximately the same
      area as the Ad5 E1a, E1b, and pIX ORFs. ORF 1 has the potential to code for a 208
      amino acid long polypeptide that is 75.5% homologous to the E1a conserved region
      III of Ad5. ORFs 2 and 3 encode 157 and 420 amino acid long polypeptide,
      respectively. The 157 amino acid polypeptides exhibits 69.3% homology to the Ad5
      small T antigen, and the 420 amino acid polypeptide exhibits 73% homology to the
      large T antigen of Ad5. ORF4 has the potential to code for a 125 amino acid long
      polypeptide that has 73% homology to the hexon-associated pIX of Ad7.

PMID- 8150593
TI  - Localization and sequence analysis of morphological transforming region III
      within human cytomegalovirus strain Towne.
AB  - A 7.6-kbp BamHI/XbaI EJ subfragment of the Towne XbaI-E fragment of human
      cytomegalovirus (HCMV) strain Towne has been previously designated as
      morphological transforming region III (mtrIII) because it induced focal and
      tumorigenic transformation of rodent fibroblasts. However, in two separate cell
      systems, mtrIII sequences were not retained because they were not detected in
      either the focal, tumor or tumor-derived cell lines. In this report, mtrIII was
      localized to a 2.1-kbp SalI/XbaI DNA fragment. The sequence of the 2,085-bp
      region was determined and compared to the colinear DNA from HCMV strain AD169.
      DNA sequence analysis revealed the presence of five open reading frames in Towne
      mtrIII, two of which are conserved in strain AD169. The localization and sequence
      analysis of mtrIII will allow further investigation as to the mechanism(s) by
      which HCMV may play a role in human cancer.

PMID- 8150594
TI  - Effects of gangliosides on the growth of herpes simplex virus type 1-infected
      cells derived from neurons and on viral replication.
AB  - Although it is well-known that herpes simplex virus can establish latent
      infections in neurons of sensory and sympathetic ganglia, little is known about
      the viral or cellular factors which regulate the latent state. Experiments were
      designed to elucidate the effects that can be produced by adding gangliosides,
      abundant components in neurons but not in most other cell types, to virus
      infected cells from mouse trigeminal ganglia and from the neuroblastoma x glioma
      hybrid cell line NG108-15. The results obtained indicate that gangliosides, when
      used in combination with acyclovir, efficiently protect the infected cells from
      lysis in both cell systems, and that they can exert antiviral activity at least
      in part via suppressing protein kinase C activity.

PMID- 8150595
TI  - Iguape: a newly recognized flavivirus from Sao Paulo State, Brazil.
AB  - A new virus, SP An 71686, was isolated from sentinel mice exposed in a forest
      area in Iguape county, Sao Paulo state, Brazil, in 1979. The results suggest
      [hemagglutination inhibition (HI), complement fixation, neutralization, and
      ELISA] that SP An 71686 virus is a new arbovirus and that it demonstrates some
      cross-reactivity with other members of the family Flaviviridae, but can be
      differentiated from them. Although there is an intensive circulation of several
      arboviruses in the area, the only diagnosed cases of human disease were caused by
      Rocio virus during and after the epidemic of encephalitis that occurred in 1975
      1977, one case of febrile illness by Caraparu virus in 1983, and by subtype IF of
      Venezuelan equine encephalitis virus in soldiers during jungle survival training
      in 1990. Wild animals had a prevalence of SP An 71686 HI monotype antibodies: 46%
      of birds captured in 1990, 40% in 1991 and 19.5% in 1992. These results suggested
      that wild birds may play a role in the virus transmission cycle. Mammals (rodents
      and marsupials) must also be considered potential hosts. However, the virus
      reservoir-vector relationships need further studies which would help to clarify
      the ecology of this virus.

PMID- 8150596
TI  - Differential behaviour in pancreas and heart of two coxsackievirus B3 variants.
AB  - In order to characterize viral kinetics and pathogenic properties of two
      intratypic variants of coxsackievirus B type 3, Balb/c mice were
      intraperitoneally inoculated and serial samples harvested from days 2 to 28.
      Although both CB3o (amyocarditic) and CB3m (myocarditic) variants induced similar
      early infectivity titres in pancreas, only the latter led to severe acinar
      necrosis, followed in turn by patent viraemia and subsequent focal myocarditis.
      Nevertheless, when both variants were inoculated in cultured cardiac cells,
      neither infectivity nor cell death rate differed noticeable. Therefore, our
      findings indicate that overt myocarditis is not attributable to contrasting
      cardiomyocyte susceptibility to the tested variants but rather to prior viral
      events in pancreatic tissues.

PMID- 8150597
TI  - Restriction endonuclease analysis and molecular cloning of porcine adenovirus
      type 3.
AB  - The 6618 strain of porcine adenovirus type 3 was cultivated in swine testis
      cells, and viral DNA was extracted from the infected cells by a modified Hirt
      procedure. The DNA was digested by each of 13 restriction endonucleases, and the
      number of cleavage sites which were identified varied from 1 to 17. The size of
      the porcine adenovirus type 3 genome, estimated from the sizes of the restriction
      enzyme fragments, was approximately 35 kb. Fragments representing the entire
      genome were cloned. Physical maps were constructed based on the results of
      restriction endonuclease analyses and hybridization and oriented with respect to
      the genome of bovine adenovirus type 3.

PMID- 8150598
TI  - Nucleotide sequence analysis of an Andean potato mottle virus middle component
      RNA cDNA clone: comparisons of the encoded proteins with those of other
      comoviruses.
AB  - Andean potato mottle virus (APMV) is a comovirus whose genomic structure consists
      of two plus-strand RNA molecules (M- and B-RNA). Here we report the nucleotide
      sequence analysis of an APMV M-RNA cDNA clone with 3,669 nucleotide (nt)
      residues, exclusive of the polyadenylate at the 3' end, covering approximately
      99% of the APMV M-RNA. The first initiation codon in register translates from nt
      194 to 3185 a polyprotein of 997 amino acid (aa) residues. A second initiation
      codon in register, beginning at nt position 416, translates a polyprotein of 923
      aa. The cleavage sites used in the processing of polyprotein were identified in
      the long open reading frame by N-terminal microsequencing of the large coat
      protein (LCP) and the small coat protein (SCP). These dipeptide cleavage sites
      are Q/M for the LCP and Q/F for the SCP. In a comparison of the deduced APMV
      polyprotein aa sequence with those of four other comoviruses, the coding regions
      for the putative movement protein, LCP and SCP, were found similar in length in
      all five species. Multiple alignment of the M-RNA sequences for each of the three
      genes from the five comoviruses revealed different degrees of homology. APMV was
      always the least homologous of the five comoviruses, showing significant aa
      substitutions in positions where the other comoviruses have identical residue or
      conservative substitutions.

PMID- 8150599
TI  - Nucleotide sequence of Johnsongrass mosaic potyvirus genomic RNA.
AB  - The complete nucleotide sequence of the RNA genome of Johnsongrass mosaic virus
      (JGMV), which infects monocotyledonous plant species, has been determined from
      cloned viral cDNAs. The JGMV genomic RNA is 9,766 nucleotides in length,
      excluding the poly (A) tail, and contains a large open reading frame that codes
      for a polyprotein of 3,052 amino acids. The open reading frame is flanked by a 5'
      untranslated region of 135 and a 3' untranslated region of 475 nucleotides. A
      comparison of the JGMV polyprotein with the sequences of other members of the
      Potyvirus genus allowed the delineation of putative proteolytic cleavage sites.
      This comparison also showed that JGMV has a genome organization that is similar
      to other members of the genus Potyvirus. As with other potyviruses, the JGMV P1
      and P3 proteins were found to be the most variable and the NIb protein the most
      conserved when compared with the corresponding proteins of other potyviruses.
      JGMV differed from other members of the genus Potyvirus in the amino acid at the 
      1 position of the putative cleavage sites of the NIa proteinase. The putative
      cleavage site for P3/CI, CI/NIa, NIa/NIb, and NIa-VPg/NIa-Pro in the JGMV
      polyprotein each contained a glutamate at the -1 position which is glutamine in
      most other potyviruses. Glutamate at the -1 position has also been observed at
      the CI/NIa-VPg junction of pea seed borne mosaic virus and turnip mosaic virus
      and at the NIb/CP junction of papaya ringspot virus polyproteins.

PMID- 8150600
TI  - Cardiovascular effects of nisoldipine in essential hypertension.
AB  - The acute hemodynamic effects of nisoldipine (Bay K552) in patients with
      essential hypertension were studied using nuclear ventriculography. In a cohort
      of 16 essential hypertension patients, an oral dose of 15 mg nisoldipine
      significantly lowered blood pressure within 20 min. The effect lasted at least 3
      h. Blood pressure that was 160.5 +/- 20.3/108.0 +/- 10.1 mm Hg initially was
      reduced to 137.0 +/- 14.9/93.8 +/- 9.4 mm Hg at 3 h (P < 0.001). Cardiac output
      rose, total peripheral resistance fell and ejection fraction rose significantly.
      End systolic and end diastolic volumes did not change significantly with this
      dose of nisoldipine. The acute hemodynamic effects of 15 mg nisoldipine
      administered orally, measured by repeat nuclear ventriculography, were maintained
      during therapy for the 8 weeks of observation. Thus, nisoldipine is a powerful
      antihypertensive agent, significantly decreasing BP as well as total peripheral
      resistance and increasing cardiac index. This effect was prominent after 3 h and
      wore off about 12 h after each dose. Five of the patients had an initially high
      heart rate. To these patients propranolol was added in small doses (20-40 mg/day,
      mean 25 +/- 26 mg/day). This addition did not change the results when the
      patients were analyzed separately.

PMID- 8150601
TI  - The yield of bone scintigraphy in cancer and non-cancer patients: its association
      with indication and clarity of the referral question.
AB  - The yield of bone scintigraphy was assessed in a general hospital. A random 1:2
      sample of the bone studies performed within a year was evaluated. The referral
      forms were judged to show absent, ambiguous or clear diagnostic questions. The
      indications for which the study was ordered were matched with the scintigraphic
      diagnosis, and yield was defined as the proportion of studies with relevant
      findings on scintigraphy. The overall yield was 23.5%. In cancer patients the
      yield was 27.2% and in repeat studies 40.2%. In non-cancer patients the yield was
      19.8% and when scintigraphy was performed for the evaluation of specific disease
      entities it was 35.7%. Relatively low-yield indications in non-cancer patients
      were suspected metastases 11.1%, and evaluation of X-ray abnormalities 11.5%. An
      association between the clarity of the diagnostic question and the scintigraphic
      yield was detected in non-cancer patients. When a diagnostic question was absent
      the yield was 12%, ambiguous 19%, and when it was clear 26%. This correlation is
      probably attributed to better understanding of this common procedure, and better
      definition of the diagnostic question in patients with diverse clinical
      conditions as compared to cancer patients in whom the question always relates to
      the presence of bone metastases.

PMID- 8150602
TI  - Intracranial tuberculoma: clinical and computerized tomographic findings.
AB  - Seven cases of intracranial tuberculoma diagnosed in northern Turkey over a 2
      year period are presented, with emphasis on the CT and clinical findings. CT
      alone cannot differentiate tuberculoma from an abscess or other granulomatous
      processes, but it is still one of the most sensitive techniques for detecting
      tuberculomas. It provides information on the nature of the lesion and the number
      of loci.

PMID- 8150603
TI  - Nisoldipine--is there a positive inotropic effect?

PMID- 8150604
TI  - Is serotonin the main culprit in depression?

PMID- 8150605
TI  - Serotonergic mechanisms in depression: clinical insights and biological
      correlates.

PMID- 8150606
TI  - New mechanisms in cholesterol gallstone disease.

PMID- 8150607
TI  - The physician's prayer of Jacob Zahalon.

PMID- 8150608
TI  - George Fernand Isidore Widal--pioneer in serology and cytodiagnostics.

PMID- 8150609
TI  - [Paraptic eczema. Why a new name?].
AB  - The new term "paraptic eczema" is proposed for a well-defined type of eczema that
      is elicited by the haematogenous action of an antigen that has already initiated
      a sensitization of the T-cell-mediated type by topical action on the skin. The
      term is composed of the Greek words "para" = " beyond, beside" and hapsis =
      "contact". Many other names have been used in the past to describe partial
      aspects of paraptic eczema, such as "haematogenous contact eczema", "dyshidrotic
      eczema", "pompholyx", "dermatophytid", or "tylotic palmar eczema", but these
      terms are inappropriate for a workable delineation of this nosological entity.

PMID- 8150610
TI  - [Catamnestic studies of patients with chronic urticaria and aspirin intolerance
      ].
AB  - Of a total of 131 patients suffering from chronic urticaria, 15 were cautiously
      re-exposed to ASA after an initial provocative exposure during an urticaria test
      programme 2-11 years before. Only 1 of these patients, who had undergone the
      initial provocative test 7 years earlier, reacted at the same intensity; 1 other
      patient reacted with much less intense symptoms 4 years after the original test.
      Among 3 other patients, who merely reacted to ASA intake with urticarial
      eruptions and did not suffer from chronic urticaria, only 1 presented 4 years
      after the initial exposure with oedema of the skin and itching. The tolerance
      threshold was markedly higher. These results suggest that the sensitivity to
      intolerance-inducing agents is reduced relatively quickly and may subside
      completely in most cases.

PMID- 8150611
TI  - [Malignant melanoma in epiluminescent microscopy].
AB  - Comparison by skin epiluminescent microscopy of 60 malignant melanomas and 130
      junctional and compound naevocellular naevi revealed statistically significant
      differences for 12 characteristics. The following microscopical in vivo signs
      that can be defined by histopathological examination were found only in malignant
      or premalignant melanocytic lesions: digitated radial streaming, greyish-blue
      reticular patterns, opaque gypseous alabaster lacunas, brown/black dots on a
      blue/greyish background, pseudopodia at the periphery and blue-in-pink areas.
      Nevertheless, specific epiluminescent phenomena of histopathologically defined
      malignant melanomas are still unknown. Therefore, diagnostic evaluation of
      malignancy is based mainly on microscopic assessment of combined details of
      morphology and colour of melanocytic tumours.

PMID- 8150612
TI  - [Transferrin concentration in seminal plasma in testicular varicocele with
      various sperm concentrations and various forms of azoospermia].
AB  - Seminal plasma transferrin concentrations were measured in semen samples from 424
      men attending a fertility unit. There was a clear positive correlation between
      seminal plasma transferrin concentration and sperm density: transferrin
      concentrations decrease with decreasing sperm density and are lowest in patients
      with azoospermia and those who have undergone vasectomy. The differences between
      the various groups in sperm density are highly significant, but individual data
      counts also vary widely. Furthermore, it was demonstrated that in polyzoospermia
      the seminal plasma transferrin concentration is increased, suggesting primary
      tubular hyperactivity. No correlations with other seminal parameters or hormonal
      values were found. Seminal plasma transferrin concentrations in normozoospermia
      and in varicocele testis or in cases with increased numbers of immature germ
      cells in the ejaculate were not significantly different. This may be interpreted
      as indicative of intact secretory activity of Sertoli cells in both varicocele
      and increased desquamation of immature germ cells. The absence of correlation
      with any of several important spermatological parameters and our inability to
      differentiate between azoospermia caused by obstruction and by tubular impairment
      indicate that seminal plasma transferrin is not a useful marker for Sertoli cell
      function or for seminiferous tubular dysfunction.

PMID- 8150613
TI  - [Subungual keratoacanthoma].
AB  - Subungual keratoacanthomas (SKA) differ in clinical presentation, biological
      behaviour and the therapy needed from keratoacanthomas in other localizations.
      Against the backdrop of two personal observations and a review of the literature,
      the authors describe clinical and histological features and also the differential
      diagnosis and therapy and this rare benign neoplasm. Patients present with a
      rapidly growing, painful subungual mass, which causes destruction of the
      underlying bone and usually does not regress spontaneously. Histological
      differentiation from squamous cell carcinoma is essential as the prognosis and
      treatment are different. SKA is treated by local excision and curettage. Erosions
      of the underlying distal phalanx usually heal spontaneously. However, persistent
      recurrences after subtotal excision often necessitate amputation of the distal
      phalanx.

PMID- 8150614
TI  - [Target-like hemosiderotic hemangioma. Further differential diagnosis of Kaposi
      sarcoma].
AB  - Targetoid haemosiderotic haemangioma (THH) can be differentiated from other
      angiomatous lesions by the characteristic findings on clinical and histological
      examination. Clinically the solitary lesion is suggestive of a melanocytic or
      angiomatous origin, surrounded by a haemorrhagic halo in the acute phase.
      Histological findings vary depending on the duration of the alteration. The
      pattern has a superficial and a deep dermal component. In the papillary body
      lesional capillaries are lined by prominent endothelial cells. The surrounding
      tissue is oedematous and contains masses of erythrocytes or haemosiderin and a
      lymphocytic infiltrate. Vessels in the deeper dermis have a lymphatic appearance
      and surround adnexal structures. Further possible similarities with Kaposi
      sarcoma are dissecting vascular lumina between collagen bundles and spindle cell
      areas. However, has no atypical cells, eosinophilic globules or apoptotic
      endothelial cells. Immunohistochemical investigations, which have now revealed
      BMA 120 for the first time in THH as well as factor VIII-R antigen and Ulex
      europaeus I lectin, have not so far made any substantial contribution to the
      differential diagnosis and histogenesis of THH, because markers distinguishing
      lymphatic from vascular endothelia are still lacking.

PMID- 8150615
TI  - [Kaposi-Irgang lupus erythematosus profundus. Lupus erythematosus panniculitis].
AB  - Lupus panniculitis is a rare variant of cutaneous lupus erythematosus. Two
      typical cases demonstrate the association of lupus panniculitis with signs of
      discoid lupus erythematosus and systemic lupus erythematosus. Clinically it is
      characterised by subcutaneous nodules or plaques, which may ulcerate leaving
      depressed atrophic scars. Histologically the lesions show lobular panniculitis. A
      positive immunofluorescent band test with deposition of IgG, IgM and C3 at the
      dermal-epidermal junction and blood vessel walls helps to confirm the diagnosis.
      The knowledge of the clinical features and histopathology of the disease is
      important because lupus panniculitis may precede systemic lupus erythematosus by
      some years.

PMID- 8150616
TI  - [Self-help groups in dermatology].
AB  - In Western Germany there are at least 2000 self-help groups concerned with
      dermatological conditions. Besides therapeutic functions, self-help groups deal
      with prophylaxis and public relations. Interaction between self-help groups and
      doctors is biased by expectations of support on the self-help groups' side and
      fears and prejudices on the doctors' side. Thus, for the benefit of their own
      patients doctors should be well informed about self-help groups working in their
      region, as the quality of help received from these groups varies widely. In this
      paper we have listed super-regional contact addresses of self-help groups.

PMID- 8150618
TI  - [Penicillamine-induced elastosis perforans serpiginosa].
AB  - Elastosis perforans serpiginosa is a rare disease with variable etiology. We
      report on a 33-year-old male patient in whom the disease was induced by long-term
      treatment with the chelating agent D-penicillamine.

PMID- 8150617
TI  - [X-chromosome dominant chondrodysplasia punctata (Happle syndrome). Lyonization
      of the eyelashes?].
AB  - X-linked dominant chondrodysplasia punctata or Happle syndrome is a rare
      hereditary disorder. The clinical features include retardation of growth,
      cataract, and temporary, ichthyosiform erythroderma. Atrophic lesions and
      hyperkeratotic papules of the skin and disturbances of hair growth follow the
      lines of Blaschko. A 5-year-old girl with X-linked dominant chondrodysplasia
      punctata was found to be mentally retarded and to have abnormalities of the
      eyelashes (growth and pigmentation), which had not previously been described in
      this condition.

PMID- 8150619
TI  - [Soft tissue and bone infections caused by dermatophytes].

PMID- 8150620
TI  - [Pigmented nevus of foot soles].

PMID- 8150621
TI  - [Symposium report: "Therapy of severe psoriasis with Sandimmune". Symposium of
      Nurnberg Sandoz AG 13 February 1993, Nurnberg].

PMID- 8150622
TI  - [The mast cell].

PMID- 8150623
TI  - [Carboxyhemoglobinemia caused by dichloromethane exposure with dermatologic
      effects].
AB  - In seven winter seasons a young watchmaker was severely disabled by the
      development of swelling and reddening of the skin, blistering and paraesthesiae
      affecting his hands. Hospital examination led to a diagnosis of "Raynaud syndrome
      of undetermined origin". Treatment with corticosteroids was unsuccessful. Not
      until the young man changed his job did the disorder disappear for good.
      Investigations at his place of work revealed that the man had inhaled
      dichloromethane fumes (methylenchloride; CH2Cl2) while cleaning watch parts in a
      small room that was not ventilated during the winter months. This led to
      endogenous carboxyneogenesis and subsequently to chronically recurring
      carboxyhaemoglobinaemia (13%, 10% and 10.7% COHb in three different blood
      samples). The significance of dichloromethane-induced CO poisoning in the
      development of dermatological changes is still the subject of controversial
      discussion.

PMID- 8150624
TI  - [Cicatricial keloids after Waterhouse-Friderichsen syndrome].

PMID- 8150625
TI  - [Spinocellular cancer in lichen sclerosus et atrophicus of the vulva].
AB  - We report on a 78-year-old woman with a 47-year-history of lichen sclerosus et
      atrophicus of the vulva on which squamous cell carcinoma developed. The lesion
      started as a small nodule that increased gradually in size and became eroded. The
      tumour and the inguinal lymph nodes on both sides were excised. Physical
      examination, chest X-ray and sonography of the abdomen 15 months later showed no
      local recurrence or distant metastases. Lichen sclerosus et atrophicus of the
      vulva should be considered a possible precancerous condition.

PMID- 8150626
TI  - [Simultaneous occurrence of extra-abdominal fibromatosis and post-traumatic
      keloid].
AB  - The report deals with the clinical features of a 26-year-old man with the
      extraabdominal form of deep fibromatosis, which became manifest at the age of 18
      years as acute ileus caused by diffuse intraabdominal fibromatous tumours. In the
      later course of the disease extensive fibromatous lesions developed, mainly at
      the skin. In addition, multiple keloids occurred after excision or after
      negligible traumas. The pathogenetic events of the clinical picture described may
      be linked to the activation of mesenchymal cells leading to the generation of
      either fibromatous tumours or posttraumatic keloids.

PMID- 8150627
TI  - [Simultaneous administration of coumarin derivatives and acetylsalicylic acid?].

PMID- 8150628
TI  - ["Ambulatory balneo-phototherapy" trial model].

PMID- 8150629
TI  - [Comment on the contribution by S. Pingel: Homeopathy--basic principles and
      applications in dermatology. A word on homeopathy].

PMID- 8150630
TI  - [Comment on the contribution by A. Schulze-Dirks and P. J. Frosch. Contact
      allergy to mephenesin].

PMID- 8150631
TI  - [Comment on the contribution by Th. Rosenbach et al. Treatment of vitiligo with
      phenylalanine and UV-A].

PMID- 8150632
TI  - [Dermatoses described in Japan. Part I].

PMID- 8150633
TI  - [Etiology of contact urticaria with special reference to occupational
      substances].
AB  - On the basis of an extensive literature search (DIMI, MEDLINE-status at June
      1992), the causes of contact urticaria so far known are displayed in tables. The
      contact urticariogens can be divided into (1) chemically defined substances and
      (2) chemically undefined biological materials. The causes most frequently
      encountered in 16 professions are given. Numerous agents are known for medical
      professions (physicians, nurses, dentists and dental technicians, veterinary
      surgeons). Today, the most frequent single cause of contact urticaria is probably
      the presence of latex proteins in rubber (gloves, condoms, tubes, balloons,
      etc.). When testing is performed a stepwise approach is recommended for safety
      reasons (rub test, prick test, scratch chamber test). For some contact
      urticariogens a commercial radioallergosorbent test (RAST) is available. In the
      cases reported in the literature it is not always possible to decide definitely
      whether the pathogenetic mechanism was immunologic (IgE mediated) or non
      immunologic (toxic or pseudoallergic). When there is a high degree of
      sensitization (e.g. to latex) professional activities must be severely
      restricted, or even completely discontinued in rare cases.

PMID- 8150634
TI  - [Therapeutic superiority of regional retrograde venous antibiotic pressure
      infusion versus systemic venous infusions in diabetic patients with infected
      neuropathic plantar ulcers].
AB  - Since systemic treatment of neuropathic plantar ulcers in diabetics (DNPU) has so
      far been rather ineffective, recent reports of successful management of DNPU by
      short-term retrograde transvenous leg perfusion (RVP) by South American
      angiologists encouraged us to apply this treatment method in diabetics suffering
      from chronic DNPU. Hence, in a prospective comparative clinical trial started in
      1989 we have treated 45 male diabetics suffering from DNPU with the same daily
      doses of netilmycin, administered either in systemic venous infusions (SVI: n =
      21, three times/day) or in RVP (n = 24, once/day). After 10 consecutive days of
      treatment, ulcers had closed in 8 of the 24 patients treated with RVP, as against
      3 of the 21 treated with SVI. Diminution of the ulcer area by > 30% including
      full debridement was achieved in 10/24 of the RVP cases (SVI: 4/21). During 6
      months of follow-up, amputation of toes or forefoot was necessary in only 1
      patient in the RVP group, but in 4 in the SVI group. Partial restitution of
      osteolytic damage was observed in some cases after RVP. Our results show that
      regional netilmycin therapy given by the RVP procedure is clearly superior to
      equal netilmycin doses administered by SVI for the treatment of DNPU. RVP can be
      recommended in DNPU, particularly when the ulcers are complicated by infections.

PMID- 8150635
TI  - [Wissler's allergic subsepsis].
AB  - A 20-year-old female patient with the typical signs of Wissler's subsepsis
      allergica (Wissler-Fanconi syndrome) is described. This rare disease is
      characterized by four typical symptoms: polymorphous exanthemas, recurrent high
      fever, leucocytosis and arthralgia. In the early stages it is difficult to
      differentiate from septicaemia. This syndrome has sometimes been considered
      equivalent to or an initial stage of Still's disease (juvenile rheumatoid
      arthritis) progressing to degenerative arthritis in many patients, whereas other
      authors have classified it as a separate entity with good prognosis. The present
      case demonstrates that Wissler's subsepsis allergica should be considered when
      ever transient polymorphous exanthema is accompanied by high recurrent fever,
      leucocytosis and arthralgia.

PMID- 8150636
TI  - [Cutaneous drug reaction caused by suramin in 4 patients with metastatic prostate
      cancer].
AB  - Suramin has long been used in the treatment of onchocerciasis and
      trypanosomiasis. Recent investigations showed an antiproliferative effect of
      suramin on prostate carcinoma cell lines. Ongoing clinical trials have confirmed
      the effect of suramin on metastasizing prostate carcinoma. Five patients with
      metastatic prostate carcinoma resistant to classic hormonal therapy were treated
      with high-dose suramin. Four of the five developed a papulovesicular or
      maculopapular rash within 2-4 weeks of starting therapy. The rashes disappeared
      after discontinuation of suramin within 10 days. In tumour therapy, high dosages
      of suramin are used to achieve a serum level of 200-300 micrograms/ml. Therefore,
      a toxic reaction to suramin is suspected as the explanation for the skin rashes.

PMID- 8150637
TI  - [Pachydermodactyly. Sequela of obsessive-compulsive neurosis].
AB  - Pachydermodactyly is an acquired, asymptomatic swelling of the lateral sides of
      the fingers and is seen mainly in young men. The formal pathogenesis is a benign
      fibromatosis. The casual pathogenesis was until now unclear, although we believe,
      that exogenic factors are the main reason. Consequently Pachydermodactyly has to
      be considered as a result of compulsion neurosis.

PMID- 8150638
TI  - [Multicentric reticulohistiocytosis and myelodysplastic syndrome].
AB  - Multicentric reticulohistiocytosis (MRH) is a rare disorder of skin and joints,
      and its aetiology is unknown. We describe a male patient who had first developed
      osteoblastic lesions of the skeleton in 1976 at the age of 59 years. Three years
      later, he presented with multiple papular and nodular skin lesions, predominantly
      on the limbs and upper trunk, and 4 years later he developed painful arthropathy.
      In 1988 skin examination showed multiple brownish-red papulo-nodules, some of
      which, at mechanically stressed areas, were ulcerated. The patient complained of
      pronounced arthrotic disorders with reduced joint mobility. Examination of biopsy
      specimens from active skin lesions demonstrated extensive numbers of macrophages
      with partial confluence to giant cells with typical ground-glass cytoplasm.
      Electron microscopy revealed phagocytosis of collagen-like-structures.
      Examination of bone marrow biopsy specimens revealed diffuse infiltration by
      histiocytic cells. The diagnosis made was therefore MRH. The patient was treated
      for several years with different therapeutic regimens, including azathioprin,
      dapsone, prednisolon, chlorambucil and cyclophosphamide, and complete remission
      of skin lesions and of bone marrow infiltration was observed. However, a
      myelodysplastic syndrome with refractory anaemia and ring sideroblasts developed,
      which is generally understood to be a preleukaemic condition. Myelodysplastic
      syndromes commonly develop between 3 and 10 years after the start of a therapy
      with antineoplastic agents.

PMID- 8150639
TI  - [Initial manifestation of bullous pemphigoid simulating dyshidrosis
      palmoplantaris].
AB  - The case of a 63-year-old woman suffering from generalized bullous pemphigoid
      with localized pemphigoid mimicking dyshidrosiform dermatitis is presented.
      Dyshidrosiform pemphigoid is an unusual variant of localized pemphigoid;
      clinically it mimics dyshidrosiform dermatitis, for example.

PMID- 8150640
TI  - Delirium tremens in acute myocardial infarction.

PMID- 8150642
TI  - Alcoholic heart disease: a review.
AB  - The association between chronic alcohol consumption and alcoholic heart disease
      in human beings is well recognized. Chronic alcohol consumption is the leading
      cause of secondary cardiomyopathy, a heart muscle disease associated with long
      term alcohol consumption. Both acute and chronic alcohol consumption have a
      negative inotropic effect on the myocardium, precipitate arrhythmias, and may
      provoke angina pectoris. There are numerous reports that alcohol changes many
      subcellular processes that are involved in excitation-contraction coupling.
      However, the exact mechanism(s) underlying these changes in the heart are still
      poorly understood. Despite the recent presumptive protective reports that
      moderate alcohol consumption protects against the risk of coronary artery
      disease, nurses and physicians must educate all patients about the many other
      adverse effects of alcohol on the cardiovascular system. The purpose of this
      article is to review and discuss the mechanism(s) that may underlie changes in
      contractile function after long-term alcohol consumption and identify current
      trends in identification and treatment of alcoholic heart disease.

PMID- 8150641
TI  - The effects of music and muscle relaxation on patient anxiety in a coronary care
      unit.
AB  - OBJECTIVE: To test the efficacy of music and muscle relaxation techniques in
      reducing the anxiety of patients admitted to a coronary care unit with ischemic
      heart disease. DESIGN: Randomized, controlled trial. SETTING: Seven-bed coronary
      care unit of an Australian tertiary care hospital. PATIENTS: Fifty-six patients
      admitted to a coronary care unit with unstable angina pectoris or acute
      myocardial infarction. OUTCOME MEASURES: Psychologic (State Trait Anxiety
      Inventory, Hospital Anxiety and Depression Scale, Linear Analogue Anxiety Scale)
      and physiologic (systolic and diastolic blood pressure and heart rate) variables
      were measured as indicators of anxiety. INTERVENTION: Two or three 30-minute
      sessions of audiotape interventions were conducted with portable tape players
      with headphones. The two intervention tapes consisted of light classical music
      and verbal instructions for muscle relaxation. RESULTS: With analysis of variance
      procedures, the null hypotheses were supported. No significant differences (p <
      0.05) between groups were demonstrated for the psychologic or physiologic
      variables; that is, no significant reductions in anxiety were achieved for
      patients using music or muscle relaxation interventions when compared with the
      control group. The effect size of the interventions on the outcome measures was
      0.19 to 0.22, indicating a small effect. Resultant power was at a low level.
      CONCLUSIONS: These results differ from those of similar studies but may be
      related to the high probability of a type II error. Further investigation with
      longer intervention sessions and larger sample sizes is indicated. Similar
      studies should incorporate power analysis when reporting their results.

PMID- 8150643
TI  - Developing a scale to measure denial levels of clients with actual or potential
      myocardial infarctions.
AB  - OBJECTIVE: To refine and test the Robinson Self-Appraisal Inventory-Form D (RSAI
      Form D), a self-administered scale designed to measure denial in coronary
      clients. DESIGN: Exploratory research. SETTING: Two midwestern medical centers.
      SAMPLE: The sample was composed of 130 patients 75 years of age and younger with
      actual or potential myocardial infarction. MEASURES: Two instruments, the
      Demographic Data Form and the RSAI-Form D, were completed by the participants.
      RESULTS: Cronbach's coefficient alpha, factor analysis, t test, and stepwise
      multiple regression were used in the data analysis. A coefficient alpha for the
      20-item scale was 0.80 for both Day 2 and Day 4. Day 2 and Day 4 oblique
      rotations revealed that items loaded on four factors but did not load on the same
      factors for both days: therefore, factors were identified for each day. There was
      a significant decrease in RSAI-Form D scores from the second to fourth
      hospitalized day (t = 5.83, p = 0.001). Two predictors, number of prior
      hospitalizations of chest pain, and whether or not the individual had sustained a
      myocardial infarction this admission (identified by stepwise multiple regression)
      explained 9.4% of the variance in the change in RSAI-Form D scores from Day 2 to
      Day 4 (F[2, 127] = 6.55, p = 0.001). CONCLUSIONS: Findings of the study did
      provide preliminary evidence that the RSAI-Form D is a reliable and valid
      inventory. Four aspects of denial were extracted, thus providing supportive
      evidence to the nurse that the use of single specific or global criteria does not
      provide sufficient data for assessing denial.

PMID- 8150644
TI  - Comparison of quality of life before and after coronary artery bypass surgery and
      percutaneous transluminal angioplasty.
AB  - OBJECTIVE: To compare quality of life, mood state, and physical functioning
      before and after revascularization in patients who have undergone coronary artery
      bypass grafting (CABG) and percutaneous transluminal angioplasty (PTCA). DESIGN:
      Quasiexperimental. SETTING: Hospital (university, Veteran's Administration,
      private) and home. SAMPLE: Patients who had undergone elective CABG (n = 44) and
      PTCA (n = 32); mean age 57.9 years (standard deviation, 8.2 years). OUTCOME
      MEASURES: Quality of life, mood state, physical functioning. RESULTS AND
      CONCLUSION: Patients who have undergone CABG and PTCA are similar in quality of
      life, mood state, and physical functioning before revascularization. Quality of
      life did not change from baseline in either group. Mood state and physical
      functioning improved for both CABG and PTCA groups after the procedure, but there
      was significantly greater improvement in the PTCA group. Future research needs to
      evaluate changes in these parameters over a longer period of time and to explore
      interventions to maximize outcomes.

PMID- 8150645
TI  - Resuscitation discussion experiences of patients hospitalized in a coronary care
      unit.
AB  - OBJECTIVE: To learn about patients' feelings, beliefs, and values concerning
      resuscitation and to suggest the role for nurses in discussion of resuscitation
      options with patients. DESIGN: Prospective, qualitative, phenomenological.
      SETTING: Midwestern teaching hospital. PATIENTS: Ten patients hospitalized in a
      coronary care unit. Age range was 67 to 89 years. RESULTS: Participants described
      beliefs about life-sustaining interventions, decision making, and patient and
      family involvement, nurses' and physicians' roles in the decision-making process,
      and desire to know the truth about their health care options. Subjects also
      offered definitions of cardiopulmonary resuscitation, resuscitation, and code in
      their own words. CONCLUSIONS: This study suggests that decision-making
      opportunities are important to patients. Because patients frequently feel
      comfortable discussing their feelings with nurses, nurses have the opportunity to
      initiate discussion of sensitive issues with patients.

PMID- 8150646
TI  - A comparison of four endotracheal tube holders.
AB  - OBJECTIVE: To compare four methods (Lillihei harness, Comfit, Dale, and
      SecureEasy) of securing endotracheal tubes in orally intubated adult patients in
      the intensive care unit. DESIGN: Prospective, quasiexperimental. SETTING:
      University-affiliated oncology critical care unit. SUBJECTS: One hundred twenty
      one adult patients who were orally intubated. OUTCOME MEASURES: Endotracheal tube
      stability, facial skin integrity, patient and registered nurse satisfaction.
      INTERVENTION: Data collection was conducted on 121 orally intubated subjects.
      Subjects were evaluated every 12 hours for stabilization of the endotracheal tube
      and integrity of facial skin. On extubation, patient and nurse satisfaction with
      the method were assessed. RESULTS: Pearson chi square revealed the SecureEasy
      holder to be the most secure (p = 0.044). Of all variables that possibly affect
      extubation, presence of prolonged coughing and gagging had the greatest impact in
      terms of accidental extubation or dislocation of the endotracheal tube. The
      fewest incidents of facial skin breakdown occurred with the SecureEasy and Dale
      holders. Patient complaints regarding discomfort with turning were least common
      with the Lillihei harness. The SecureEasy holder was associated with the highest
      degree of nurse satisfaction. CONCLUSIONS: Results of this study suggest that the
      SecureEasy holder is the preferred alternative method for securing endotracheal
      tubes when the standard method with tape is not desirable. These results are
      similar to those reported in a previous investigation in which the adequacy of
      the SecureEasy holder was assessed.

PMID- 8150647
TI  - Pneumothorax after thoracentesis in chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine whether the frequency of pneumothorax is increased after
      thoracentesis in chronic obstructive pulmonary disease patients. DESIGN:
      Prospective. SETTING: Northeastern community hospital. PATIENTS: One-hundred-six
      patients underwent multiple thoracentesis; 36 patients had co-existent chronic
      obstructive pulmonary disease (mean age, 68.2 years). Chronic obstructive
      pulmonary disease was identified by radiologic findings consistent with chronic
      obstructive pulmonary disease and as forced expiratory volume in one second less
      than 70% of predicted. OUTCOME MEASURES: Identification of pneumothorax on chest
      roentgenogram after thoracentesis. INTERVENTION: Patients had diagnostic or
      therapeutic thoracentesis with follow-up chest radiography within 2 hours, or
      sooner if clinically indicated. RESULTS: Patients with chronic obstructive
      pulmonary disease had a higher incidence of pneumothorax (15 of 36 patients;
      41.7%) than those patients without underlying chronic obstructive pulmonary
      disease (13 of 70 patients; 18.5%; p = 0.005). The frequency of pneumothorax was
      no different according to who performed the procedure (house staff or
      pulmonologist), whether it was for diagnostic or therapeutic reasons, and whether
      a small (< 500 ml) or large (> 500 ml) amount of fluid is removed. CONCLUSION:
      Pneumothorax may frequently occur in patients with chronic obstructive pulmonary
      disease undergoing thoracentesis. The reason may be related to the altered
      architecture of the lung parenchyma and the change in mechanical forces in
      chronic obstructive pulmonary disease. Sonography-guided thoracentesis may offer
      a safer means of performing thoracentesis in patients with chronic obstructive
      pulmonary disease.

PMID- 8150648
TI  - Working in an intensive or non-intensive care unit: does it make any difference?
AB  - OBJECTIVE: To compare intensive care unit and non-intensive care unit nurses
      regarding work situation characteristics (e.g., work pressure), reaction
      variables (e.g., job satisfaction), and individual and psychosocial
      characteristics (e.g., need for autonomy) to explore whether it is more stressful
      to work on an intensive care unit than on a non-intensive care unit. DESIGN:
      Descriptive, correlational study. SETTING: Sixteen randomly selected general
      hospitals in The Netherlands. SAMPLE: 561 intensive care unit and non-intensive
      care unit nurses from 36 nursing units. MEASUREMENTS: Subjects completed a survey
      questionnaire with items derived from the Job Diagnostic Survey, the Leader
      Behavior Questionnaire, the Organizational Stress Questionnaire, and the Utrecht
      Coping Questionnaire. MAIN OUTCOME MEASURES: The outcome measures were work
      related variables including work pressure, autonomy, feedback and clarity, job
      satisfaction, experienced job significance, health complaints, absence frequency,
      social support, need for autonomy, and coping strategies. MAIN RESULTS: The
      results of the study showed that nurses who work in intensive care units had more
      positive scores than nurses who work in non-intensive care units. Thus the
      assumptions that intensive care units present more stressful work situations and
      that intensive care unit nurses show more negative reactions to their work were
      not supported in this study. CONCLUSION: The results indicate non-intensive care
      unit nurses may have a greater need for interventions in the work situation.

PMID- 8150649
TI  - Expert system development in nursing: implications for critical care nursing
      practice.
AB  - OBJECTIVE: To obtain information about how highly experienced critical care
      nurses reason to plan care and make decisions about a critically ill unstable
      patient, and to determine the usefulness of this information for expert system
      development. DESIGN: Descriptive, using think-aloud technique and protocol
      analysis. SETTING: Laboratory. PATIENT: A simulated patient case whose condition
      deteriorated over a 12-hour shift. The case depicted an elderly female with
      congestive heart failure and atrial fibrillation with rapid ventricular response.
      RESULTS: Protocol analysis revealed the information (data) that subjects used and
      how they structured that information to plan care and make decisions. Examination
      of subjects' reasoning processes allowed the investigators to identify "if-then"
      rules that could be used in expert system design. CONCLUSIONS: The reasoning
      processes identified would assist in expert system development. An expert system
      designed to represent experienced critical care nurses' knowledge and reasoning
      processes would preserve that expertise in a computer system that could then be
      used to assist less experienced nurses to improve their reasoning skills and
      strategies.

PMID- 8150650
TI  - An unusual cause of pulmonary barotrauma during apneic oxygenation testing.

PMID- 8150651
TI  - Does antiseptic make a difference in intravascular device-related complications?

PMID- 8150652
TI  - Spurious ST segment elevation.

PMID- 8150653
TI  - Spotlight article: the effects of alcohol intoxication on the initial treatment
      and hospital course of patients with acute brain injury. (Gurney JG, Rivara FP,
      Mueller BA, Newell DW, Copass MK, Jorovich GJ. J Trauma 1992;33:709-13.).

PMID- 8150654
TI  - Cumulative index volumes 11-22. January 1994.

PMID- 8150655
TI  - Reproductive isolation between two species of flour beetles, Tribolium castaneum
      and T. freemani: variation within and among geographical populations of T.
      castaneum.
AB  - Tribolium castaneum and T. freemani produce sterile hybrid progeny in reciprocal
      crosses. The reciprocal crosses differ significantly in the mean numbers of
      progeny, progeny sex ratios, hybrid male body size and male antennal and leg
      morphologies. These results suggest an effect of either the X chromosome or the
      cytoplasm on characteristics of F1 hybrids. In contrast, large X chromosome
      effects on morphological traits are not usually observed in interspecific crosses
      among drosophilid flies. We also report large, significant differences in progeny
      numbers, body mass and degree of female bias in sex ratio between different
      geographic strains of T. castaneum when mated in reciprocal crosses with T.
      freemani. Sex ratio bias also varies significantly among matings within
      geographic strains of T. castaneum. When T. castaneum males are mated with T.
      freemani females, but not in the reciprocal cross, the F1 sex ratio is female
      biased, uncorrelated with family size and ranges from 57.14 per cent to 72.23 per
      cent female, depending on the geographic strain of the T. castaneum male.

PMID- 8150656
TI  - Postcopulatory, prezygotic isolation in flour beetles.
AB  - We report the existence of postmating but prezygotic reproductive isolation
      within flour beetles of the genus Tribolium. Specifically, when a female of
      either T. castaneum or T. freemani is paired simultaneously with both a
      conspecific and a heterospecific male, virtually all of the offspring are sired
      by the conspecific male. In contrast, when a female of either species is paired
      only with a heterospecific male, she produces near normal numbers of offspring.
      Mate choice experiments rule out the possibility that premating reproductive
      isolation accounts for this phenomenon. A number of different mechanisms could
      explain this phenomenon of postmating but prezygotic reproductive isolation.

PMID- 8150657
TI  - Effect of genetic architecture on the power of human linkage studies to resolve
      the contribution of quantitative trait loci.
AB  - The effect of genetic architecture (linkage relationships, dominance and two
      forms of non-allelic interaction) on the power of marker studies to detect,
      locate and analyse the contributions of specific quantitative trait loci (QTLs)
      to continuous human traits is considered for randomly mating populations in
      linkage equilibrium under a two-locus model. The expected regression of the
      within-sibling-pair mean-square on number of alleles identical by descent (IBD)
      at two marker loci is explored for every possible pair of markers over a region
      of the genome containing two QTLs linked loosely (50 CM) or more tightly (20 CM).
      For the cases examined, it is shown that epistasis between the pair of QTLs
      reduces considerably the total amount of information available for the location
      and analysis of the QTL effects. The overall effects of epistasis are more marked
      when there are duplicate gene interactions (i.e. genes operate in parallel) than
      when there are complementary interactions (i.e. genes operate in series).
      However, when there are complementary interactions, the regression approach is
      almost certain to fail to detect any evidence of epistasis. The numerical
      analysis suggests that methods of QTL analysis based on IBD in humans are
      unlikely to offer the resolving power that is desirable if QTLs are to be located
      precisely unless inheritance is very simple or prohibitively large numbers of
      highly selected individuals are available.

PMID- 8150658
TI  - Efficiency of autometallographic detection of mercury in the rat kidney.
AB  - The autometallographic silver enhancement method is a method for subcellular
      localization of some heavy metals, such as mercury. However, no quantitative
      estimate has been made of the amount of mercury demonstrated by the method. In
      this study, pellets of autometallographic silver grains were prepared from
      unfixed kidney slices of rats exposed i.p. to mercury chloride containing trace
      amounts of 203Hg. The slices were silver-enhanced, and subsequently all organic
      material was removed by enzymatic digestion. During all stages of the experiment
      the solutions and tissue were gamma-counted. The analysis showed that the final
      pellets contained approximately 30% of the mercury compared to that found in the
      slices prior to development and that the mercury was probably located in
      lysosomes.

PMID- 8150659
TI  - Cytochemical study of the effect of aluminium on cultured brain microvascular
      endothelial cells.
AB  - The cytotoxic effect of aluminium was studied on cultured goat brain
      microvascular endothelial cells used as an in vitro model of the blood-brain
      barrier. Confluent monolayers of these cells were exposed for 4 days to aluminium
      maltol and, for control purposes, to maltol alone, and also to cadmium chloride
      as a known cytotoxic substance. The localization of plasmalemma-bound enzymatic
      activities of 5'-nucleotidase and Ca(2+)-ATPase and the distribution of sialic
      acid residues were studied at the ultrastructural level. It was observed that the
      reaction for 5'-nucleotidase activity was only insignificantly affected,
      indicating its resistance to the cytotoxic action of both substances used. On the
      contrary, the activity of Ca(2+)-ATPase was evidently suppressed, especially in
      the interendothelial clefts where junctional complexes are presumably to be
      formed. Aluminium also affects the density of sialic acid residues, as shown by
      their redistribution, leading to the appearance of relatively long segments of
      unlabelled apical cell surface. The data obtained suggest that observed changes
      in the localization of Ca(2+)-ATPase and sialic acid residues can lead ultimately
      to impairment of the formation and maintenance of intercellular junctions and to
      disturbances in the negatively charged domains of the endothelial cell surface.
      Whether these alterations, induced in vitro, contribute to in vivo disturbances
      of blood-brain barrier function requires further experimental study.

PMID- 8150660
TI  - Ultrastructural localization of tumour necrosis factor-alpha.
AB  - The application of an antibody against tumour necrosis factor-alpha (TNF) to thin
      sections of plastic-embedded mouse tissue has identified sites of TNF activity in
      normal and endotoxin-treated C3N/HeN mice. Prior to endotoxin treatment, TNF was
      observed in the secretory granules of the antibacterial Paneth cell and one type
      of crypt endocrine cell. Four hours after endotoxin treatment, these two types of
      intestinal cell were found to have degranulated. In addition, endotoxin treatment
      resulted in the appearance of TNF in the secretory granules of all eosinophils,
      neutrophils and monocytes in the bone marrow, spleen, lung and the proximal
      intestine. TNF was also observed in the internal elastic lamina (IEL) of
      arterioles. These results suggest that the process of TNF induction specifically
      targets the immune system and the vasculature. An invasive stimulus, such as
      circulating endotoxin, can provoke the immune cells to be armed with TNF. That
      same stimulus may cause arteriole smooth muscle cells to secrete TNF. TNF
      secretion in the presence of arteriole smooth muscle cells may play a role in the
      adjustment of arteriole tone. In the venules, TNF may be responsible for platelet
      and neutrophil accumulation which leads to embolism formation.

PMID- 8150661
TI  - Kinetic characterization of phosphoenolpyruvate carboxylase extracted from whole
      leaf and from guard-cell protoplasts of Vicia faba L. (C3 plant) with respect to
      tissue pre-illumination.
AB  - Whole leaves and guard-cell protoplasts of the C3 plant Vicia faba L. (broad
      bean) were separately extracted following a period of illumination or following a
      period of darkness. Kinetic parameters of phosphoenolpyruvate carboxylase (PEPC,
      EC 4.1.1.31), Vmax and Km(PEP.Mg), were determined as a function of assay pH (7.0
      or 8.1), the presence of 5 mM glucose-6-Pfree (Glc-6-P, an activator), and the
      presence of 5 mM malatefree (an inhibitor). On the basis of these parameters,
      guard-cell PEPC was distinguished from that of whole leaf, indicating either that
      guard cells contain a unique isoenzyme of PEPC or a different complement of
      isoenzymes or--and less likely--that the obligatorily different methodologies for
      the leaf (intact organ) and the guard-cell (protoplast) enzymes altered them
      specifically. The values of Vmax were relatively unchanged, regardless of assay
      conditions or tissue pretreatment. The values obtained for whole-leaf PEPC Vmax
      were restricted to a small range (52.4 +/- 5.9 (SD) to 64.4 +/- 4.8 (SD) mumol.g
      fresh mass-1.h-1; the high value coincided with the presence of Glc-6-P, and the
      low value was obtained in the presence of malate. Guard-cell PEPC Vmax was also
      restricted to a small range: 7.48 +/- 0.89 (SD) pmol.guard-cell pair-1.h-1 (pH
      8.1, light, +Glc-6-P) to 5.79 +/- 0.60 (SD) pmol.guard-cell pair-1.h-1 (pH 7.0,
      dark, +malate). Depending on effectors, and particularly pH, large changes in
      Km(PEP.Mg) were calculated (whole-leaf PEPC: 0.03 to 3.84 mM; guard-cell PEPC:
      0.06 to 3.43 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150662
TI  - The localization of mercury and metallothionein in the cerebellum of rats
      experimentally exposed to methylmercury.
AB  - Rats were dosed with methylmercuric chloride, either by gastric gavage (5 x 10 mg
      kg-1 body weight over a 15-day period), or in their drinking water (20 mg
      methylmercuric chloride l-1 for 14 or 42 days). Localization of mercury within
      the cerebellum was performed with a silver physical development technique, and
      metallothionein with dinitrophenyl hapten-sandwich immunohistochemistry. Mercury
      was detected in structurally undamaged Purkinje neurones and adjacent Bergmann
      glial cells; no mercury was detected in granule cells even though these small
      cells nearest the Purkinje layer had a high incidence of pyknotic nuclei. In
      general, metallothionein was detected mainly in Bergmann glial cells, Purkinje
      cells, astrocytes and glial cells of white matter; no metallothionein was
      detected in granule cells. We hypothesized that the resistance of Purkinje cells
      to methylmercuric chloride reflects their ability to transform organic mercurials
      to inorganic mercury that, in turn, induces the synthesis of radical-scavenging
      metallothionein molecules.

PMID- 8150663
TI  - Immunocytochemical identification of murine and human megakaryocyte colonies in
      soft-agar cultures.
AB  - Murine megakaryocyte (MK) colonies in soft-agar cultures were
      immunocytochemically stained with platelet antiserum and an immuno-alkaline
      phosphatase procedure. Subsequently, cytochemical staining for
      acetylcholinesterase was used to confirm the specificity of the immunolabelling
      technique. The correlation of numbers of megakaryocyte colonies enumerated by
      independent observers was excellent. A comparable platelet antiserum directed
      against human platelet epitopes was utilized to identify human MK colonies in
      soft-agar cultures of human bone marrow. Using this method, we determined that
      the frequency of detectable human MK colonies in our agar culture system was
      maximal between days 10 and 12. The immunocytochemical staining technique we have
      developed for identification of MK colonies in soft-agar cultures yielded good
      cellular morphology and produced an intensely specific label against a clear
      background; it therefore facilitated accurate enumeration of MK colonies. This
      non-fluorescent method avoids dependence upon a non-permanent marker, and allows
      the simultaneous enumeration of positive and negative colonies.

PMID- 8150664
TI  - 6-Iodoacetamidofluorescein labelling to assess the state of sulphhydril groups
      after thermal stabilization of isolated nuclei.
AB  - Isolated nuclei and nuclear matrices, prepared from mouse erythroleukaemia cells,
      were reacted with the sulphhydryl-specific dye 6-iodoacetamidofluorescein. To
      determine whether in vitro formation of disulphide bonds might play a role in the
      nuclear matrix stabilization triggered by exposure of isolated nuclei to the
      physiological temperature of 37 degrees C, a variety of techniques were employed
      to assess the state of cysteinyl residues after such an incubation. Both flow
      cytometry and confocal microscopy quantitative analysis did not reveal major
      differences in the fluorescence intensity of nuclei incubated at 37 degrees C in
      comparison with those maintained at 0 degrees C. Confocal scanning laser
      microscopy revealed that 6-iodoacetamidofluorescein labelled a fibrogranular
      network in isolated nuclei. The fluorescent pattern of the network was not
      affected by a 37 degrees C exposure of nuclei. However, such a network was not
      detectable in isolated nuclear matrices, thus suggesting a possible protein re
      arrangement during matrix preparation. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis of fluorescent-labelled nuclear proteins showed no difference
      between heat-exposed and control samples. We conclude that oxidation of cysteinyl
      residues is not a major factor leading to the stabilization of nuclei incubated
      at 37 degrees C.

PMID- 8150665
TI  - Double labelling of major histocompatibility complex molecules and lysosomal
      protein lamp-1 on human dendritic cells.
AB  - In this study, double labelling for major histocompatibility complex (MHC) class
      I and class II molecules and for MHC molecules and the lysosomal membrane protein
      lamp-1 on ultrathin cryosections of dendritic cells isolated from human
      peripheral blood was performed. The plasma membrane proved to be positive for
      both MHC class I and MHC class II molecules and was labelled for only a very few
      lamp-1 molecules. MHC class I and MHC class II molecules did not co-localize
      intracellularly except in some peripherally located vesicles. However, many MHC
      class II-labelled vesicles were present in a juxtanuclear position but only some
      of them were co-labelled for lamp-1. These results indicate the presence of a
      separate, non-lysosomal compartment for class II molecules in dendritic cells.

PMID- 8150666
TI  - [Illnesses caused by indoor air pollution].

PMID- 8150667
TI  - [Early and late damage to the auditory and vestibular area after meningitis in
      childhood and adolescence].
AB  - Meningitis is still one of the serious infectious diseases in clinical practise.
      In a high percentage of cases with this disease process, the auditory and
      vestibular parts of the inner ear are damaged. In this study the auditory and
      vestibular systems of 53 children and teenagers between 1.7 and 18.7 years of age
      were examined following meningitis. The mean time-interval between meningitis and
      examination was 5.8 years. Eighty-one of 106 ears examined showed sensorineural
      hearing losses which varied between mild hearing loss and total deafness.
      Peripheral vestibular lesions were found in 60 of 106 labyrinths examined. These
      varied between inhibition and total loss of function. In addition, we also found
      central vestibular lesions in 29 cases. Mild and moderate combined auditory and
      vestibular lesions could be verified in 23 ears, whereas profound functional
      disturbances or functional losses were found in 29 ears examined. Eight of 40
      ears with hearing losses and 12 of 40 ears with peripheral vestibular lesions
      showed progression during follow-up. The findings of this study emphasize the
      need for auditory and vestibular diagnostic studies followed meningitis in
      children and teenagers. Patients and their families should be cared for on a long
      term basis to avoid social and psychological problems.

PMID- 8150668
TI  - [Tinnitus--often a common nuisance to patients and experts. Why does troublesome
      tinnitus turn the afflicted person into a troublesome patient?].

PMID- 8150669
TI  - [Social support, disability, coping with stress and personality markers in
      patients with subjective chronic aural tinnitus and a clinical control group].
AB  - The inhibition of physiological habituation in patients with chronic aural
      tinnitus extends from the level of cellular processing to psychologic and
      psychosocial determinants. The following hypotheses were tested in 32 patients
      with chronic tinnitus and 30 patients of a comparable clinical control group:
      tinnitus patients differ concerning (1) the perception of social support, (2) a
      disposition to psychosomatic diseases, (3) coping with stress and (4) certain
      personality traits. Standard psychological tests were used as well as a detailed
      examination of at least 30 minutes. Results showed that the tinnitus patients
      statistically perceived less social support and more social distress compared to
      the control group. They also showed significantly poorer results in coping with
      stress. Increased social distress in a number of cases resulted in noticeable
      decompensation. Additionally, a disposition to psychosomatic disorders increased,
      so that conflicts arising expressed themselves in various functional diseases. In
      most cases psychiatric exploration showed a vocational or familial overcharge. In
      patients experiencing decompensation, close cooperation with a psychotherapist is
      required.

PMID- 8150670
TI  - [Pleomorphic parotid adenomas and their recurrence].
AB  - Even today, a wide variety of techniques are performed in parotid pleomorphic
      adenoma surgery, ranging from enucleation to total parotidectomy. This study
      reports the results of our experiences. Among a total of 587 surgically treated
      parotid lesions at the Homburg/Saar University ENT Department from 1968 through
      1991, 205 were parotid pleomorphic adenomas. Among these, 166 patients received
      primary surgery at our department. Twenty-one enucleations led to 3 recurrent
      tumors (14%), while 108 superficial parotidectomies had 3 recurrences (2.8%).
      Fifteen extended superficial parotidectomies also produced 3 recurrences (20%)
      and 22 total parotidectomies had one recurrent case (4.5%). The overall
      recurrence rate was 6%, but increased to 8.3% in 5 years, 9.5% in 10 years and
      12.5% in 15 years follow-up. The "true" overall recurrence rate after 10 years
      was estimated to be between 9.5 and 20% and that for lateral parotidectomies
      between 4.4 and 13%. Patients younger than 30 years of age at the time of primary
      surgery developed a tumor recurrence in 17% of all cases. The overall recurrence
      rate following secondary surgery was 13%. Clinical findings and surgical
      techniques for resections of pleomorphic adenomas and their recurrences are
      discussed. Segmental parotidectomy is the preferred treatment, but may have to be
      changed locally to enucleation in some cases in order to preserve the facial
      nerve.

PMID- 8150671
TI  - [Reconstruction of oral cavity and oropharyngeal defects with a pure muscle
      fascia flap].
AB  - As a rule carcinomas of the oral cavity and oropharynx are not diagnosed in early
      stages. Surgical resections of these tumors including margins of safety
      invariably result in large defects. At present, one-stage flap techniques are
      preferred for reconstruction, as exemplified by pectoralis major myocutaneous
      flaps and free revascularized jejunum grafts. The skin island of the myocutaneous
      flap is underlayed by fat tissue as a sliding surface. Temporary sutures are
      necessary but have the disadvantage of producing a convex configuration. This
      shape compromises anatomical reconstruction of the oral cavity and oropharynx.
      Robertson et al. in 1985 demonstrated an alternative method for a muscle-fascia
      flap from the pectoralis major muscle. In comparison to the temporalis muscle
      fascia flap, the pectoralis muscle-fascia flap is associated with a lesser
      incidence of complications. Although it is still too early to conclude their
      definitive use, their application in some cases is now being questioned because
      of such factors as reduced time of anesthesia.

PMID- 8150672
TI  - [Therapy of hypopharyngeal cancer. Part I. Review of the literature: Surgery
      and/or radiotherapy].
AB  - On the basis of a literature review of the last 20 years concerning the surgical
      and/or radiotherapeutic management of hypopharyngeal carcinoma (and in
      particular, pyriform sinus carcinoma), the indications for therapy are presented
      and the results of loco-regional control, organ preservation, quality of life and
      complications analyzed critically. Using this material and in the following
      publications, the applications of chemotherapy and its results in treatment are
      discussed. The concept of minimally invasive therapy is presented, especially as
      it involves transoral function preservation laser microsurgery and its long-term
      results.

PMID- 8150673
TI  - [Indoor air pollution by emissions from individual fossil fuel stoves. Possibly a
      so-far underestimated risk factor in development of cancers of the head and neck
      area].
AB  - We have carried out three case-control studies on the relative risk of head and
      neck cancer in association with indoor air pollution. The studies performed at
      the Department of Otorhinolaryngology of the University of Heidelberg comprised
      369 male patients with squamous cell carcinomas of the oral cavity, pharynx and
      larynx; one thousand, four hundred and seventy-six healthy subjects were used as
      controls and were matched for sex, age and residential area. The relative risk
      (RR) of laryngeal cancer related to daily exposure to fossil fuels due to stove
      heating with oil, coal, gas and wood in a period longer than 40 years was 2.5
      [confidence interval (CI): 1.51-4.05]. After adjustment for tobacco and alcohol
      the RR declined slightly to 2.0 [CI: 1.10-3.46] but was still significant.
      Increased risks were also found for daily exposure in a kitchen containing air
      oil, coal or wood oven for a period longer than 40 years (RR = 1.7; CI: 1.01
      2.71). In this latter group the RR because 1.4 after adjustments for use of
      tobacco and alcohol [CI: 0.76-2.41]). The RR of pharyngeal cancer related to
      daily exposure to fossil fuels due to stove heating with oil, coal, gas and wood
      in a period longer than 40 years was 3.6 [CI: 2.04-6.41]. After adjustments were
      made for tobacco and alcohol, the RR declined slightly to 3.3 [CI: 1.43-7.55] but
      was still significant. Elevated risks were also found for daily presence in a
      kitchen with oil, coal or wood ovens for a period longer than 40 years (RR = 1.6
      [CI: 0.89-2.77].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150674
TI  - [Studies of sound condition in the reconstructed middle ear with a hydrophone.
      Initial results].
AB  - The acoustic result following reconstruction of the middle ear is often
      disappointing and unpredictable. Apart from biologic factors, this is due to
      insufficient knowledge of the mechanism of sound transmission through the
      operated middle ear. Therefore, temporal bone experiments with simulated middle
      ear operations were set up to investigate the sound transmission following
      different prosthesis' designs, materials, etc. We developed a tiny hydrophone
      which has a frequency range from 100 Hz to 10 kHz in order to measure the sound
      pressure in the cochlear fluid. By comparing the sound pressure in the inner ear
      with the sound pressure at the drum membrane, we were able to analyze the
      transfer function of the manipulated middle ear. First results with different
      reconstruction techniques, prosthesis' designs and attachments demonstrated the
      usefulness of this measuring technique for the development of acoustically better
      middle ear reconstructions.

PMID- 8150675
TI  - [Detection of inactivity of the auditory system in the beginning stage with the
      Freiburg masked speech test].
AB  - Late-onset auditory deprivation or "inactivity" phenomenon has been reported in
      single cases only because it has not been possible to assemble a larger number of
      calculable cohorts for which all necessary details concerning individual
      histories are available. Subjects should not be older than 60 years of age and
      should have had asymmetric hearing for at least about 10 years or should have
      been wearers of monaurally fitted hearing aids. The development of late-onset
      auditory deprivation is presented in 6 single cases. All were assessed by the
      Freiburg speech discrimination test and the distorted Freiburg speech test, with
      the latter showing greater sensitivity and variability. It is of special interest
      that the quotient of distorted speech is reduced in subjects who have normal
      hearing in one ear and considerable hearing loss in the other ear (for example,
      in the case of unilateral microtia). This effect may be evidence for significant
      activation of hearing selectivity developing in the brainstem versus
      inactivation.

PMID- 8150676
TI  - [Does esthetic surgery serve a function?].
AB  - The present paper discusses to aesthetic surgical corrections in the facial
      region. The article reflects the personal considerations of the author in regard
      to indications, psychological evaluations and conditions of patients for such
      surgery.

PMID- 8150677
TI  - Regional licensure by endorsement: New England boards test the waters.

PMID- 8150678
TI  - Gastropexy for treatment of gastric torsion/dilatation in dogs.

PMID- 8150679
TI  - More on feral cats.

PMID- 8150680
TI  - Use of anabolic steroids in horses.

PMID- 8150681
TI  - Oral and dental disease in cats.

PMID- 8150682
TI  - Canine pyoderma.

PMID- 8150683
TI  - Immune suppression challenges bovine practitioners.

PMID- 8150684
TI  - What is your diagnosis? Pneumomediastinum and severe bilateral pneumothorax.

PMID- 8150685
TI  - Animal behavior case of the month. Aggression by a dog toward the owners for at
      least 7 years.

PMID- 8150686
TI  - Hazards in the hospital.
AB  - In an earlier article (JAVMA, Jan 15, 1994), the author outlined some of the
      first steps necessary in establishing a hospital safety program that will comply
      with current Occupational Safety and Health Administration (OSHA) guidelines. One
      of the main concerns of the OSHA guidelines is that there be written plans for
      managing hazardous materials, performing dangerous jobs, and dealing with other
      potential safety problems. In this article, the author discusses potentially
      hazardous situations commonly found in veterinary practices and provides details
      on how to minimize the risks associated with those situations and how to
      implement safety procedures that will comply with the OSHA guidelines.

PMID- 8150687
TI  - A veterinarian's liability to employees.

PMID- 8150688
TI  - AVMA Animal Welfare Forum: The Veterinarian's Role in Farm Animal Welfare.
      Rosemont, Illinois, November 5, 1993.

PMID- 8150689
TI  - A special relationship: the coevolution of human beings and domesticated animals.

PMID- 8150690
TI  - Realities of contemporary livestock production.

PMID- 8150691
TI  - Farm animal welfare during handling, transport, and slaughter.

PMID- 8150692
TI  - Welfare of companion livestock: keeping large animals as pets.

PMID- 8150693
TI  - Practices of concern.

PMID- 8150694
TI  - Animal welfare in Europe.

PMID- 8150695
TI  - The veterinarian's role in farm animal welfare: directions in production and
      practice.

PMID- 8150696
TI  - Lymphocele in a cat.
AB  - A 21-month-old spayed domestic shorthair cat was examined to determine the cause
      of a chronic fluctuant swelling involving the left hind limb. A lymphocele was
      tentatively diagnosed on the basis of results of blood tests, radiography, and
      cytologic examination. Lymphangiography revealed the lymphocele and 2 tortuous
      collateral lymphatic channels. The lymphocele and a mass of fatty tissue were
      excised and 3 aberrant lymphatic vessels were ligated. Histologic examination did
      not reveal evidence of neoplasia. The cyst wall was composed of a layer of
      collagen and fibroblasts. The mass was an inflammatory nodule incorporating a
      lymphatic vessel. The authors believe this cat had an acquired lymphocele. The
      exact cause of lymphoceles is uncertain, but acquired lymphoceles have been
      reported secondary to tissue trauma or surgery in human beings. Treatment has
      included aspiration, tube drainage, open drainage and second-intention healing,
      surgical excision, ligation of lymphatic vessels, and chemical sclerosis of the
      cyst.

PMID- 8150697
TI  - Primary IgG secreting plasma cell tumor in the gastrointestinal tract of a dog.
AB  - A mixed-breed dog, evaluated because of a chronic history of diarrhea and
      intestinal bleeding, was found to have a multilobular mass involving the
      intestine. Surgical resection of the mass necessitated an ileocolic anastomosis.
      On the basis of histologic and electron microscopic appearance and staining
      characteristics, a tentative diagnosis of intestinal carcinoid was made. Recovery
      was uncomplicated; the owners declined further diagnostic tests or treatment.
      Eight weeks later, the dog was reexamined because of signs consistent with
      hyperviscosity syndrome and hyperproteinemia. At the owner's request, the dog was
      euthanatized. At necropsy, extensive metastases to liver and lymph nodes, but not
      to bone, were seen. Reevaluation of the intestinal mass supported classifying the
      tumor as an IgG-secreting extramedullary plasmacytoma. This case underscores the
      need for additional histologic techniques, especially when confronted with an
      unusual manifestation of hyperproteinemia.

PMID- 8150698
TI  - Postoperative complications and prognostic indicators in dogs and cats with
      septic peritonitis: 23 cases (1989-1992).
AB  - Medical records of 21 dogs and 2 cats treated for septic peritonitis were
      reviewed. Animals were between 1 and 12 years old, (mean, 6.5 years) and weighed
      between 6 and 51.4 kg (mean, 22.7 kg). Overall, 13 animals survived and were
      discharged from the hospital. Immediately after surgical correction of the
      underlying cause of peritonitis, most animals were tachycardic (mean heart rate,
      148 beats/min; range, 80 to 204 beats/min), and many were hypotensive (mean
      arterial pressure, 84.4 mm of Hg; range, 44 to 156 mm of Hg). Hypotension was
      attributed to sepsis and hypovolemia secondary to extensive loss of fluid into
      the peritoneal cavity. Survivors did not differ from nonsurvivors with regard to
      mean arterial pressure immediately after surgery, and in most animals,
      hypotension could be corrected by IV administration of fluids. Three animals died
      after failing to respond to fluid treatment, despite concurrent administration of
      inotropic or pressor agents. Mean rate for crystalloid fluid administration was
      12.8 ml/kg of body weight/h (range, 5 to 23.5 ml/kg/h) during the first 24 hours
      after surgery. Six of 23 animals had low urine output for a short time after
      surgery, but urine output increased when fluids were administered.
      Hypoalbuminemia developed in all animals (mean serum albumin concentration, 1.17
      g/dl; range, 0.6 to 2.3 g/dl), and peripheral edema developed in 13. Neither
      lowest mean serum albumin concentration nor fluid administration rate was
      significantly different between animals that developed peripheral edema and those
      that did not. Fluid administration rates were significantly higher in
      nonsurvivors (15 ml/kg/h; range, 5.5 to 23.5 ml/kg/h) than in survivors (11
      ml/kg/h; range, 5 to 17.5 ml/kg/h).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150699
TI  - Inflammatory response to clostridial vaccines in feedlot cattle.
AB  - In 24 individually housed feedlot steers that weighed 275 kg, clostridial
      vaccines were compared for size of injection site reactions, systemic
      inflammatory response caused by vaccination, and impact on feed consumption.
      Vaccines were a bacterin/toxoid containing antigens from multiple clostridial
      species (7-way), and a Clostridium perfringens type C and D toxoid; sterile
      physiologic saline solution was used as the control. Injection site reactions
      were observed in all vaccinated cattle. Differences in size of lesions were
      found, with cattle given the 7-way vaccine (7-way group) having the largest
      lesions. The inflammatory-response to vaccination, measured by serum
      concentration of the acute-phase protein haptoglobin, was significantly (P <
      0.05) increased in both vaccinated groups over that of controls. However, the 7
      way group had higher postinjection values than did the group given type C and D
      toxoid. The 7-way group had a significant (P < 0.05) 20% decrease in feed
      consumption in response to the second injection of vaccine. These findings are
      indicative of potential negative effects of multiple clostridial vaccinations.

PMID- 8150700
TI  - Internal fixation of bilateral mandibular body fractures in a steer.
AB  - Bilateral fractures of the mandible were identified in a 9-month-old mixed-breed
      beef steer, used for show, that had been hit by a car 8 hours prior to admission.
      The fractures involved the left interdental space and the premolar region of the
      right hemimandible. For maximal cosmesis, fractures were repaired via internal
      fixation by use of a medially positioned broad dynamic-compression plate and
      cerclage wire. A medial approach served to protect more laterally located
      vascular and nervous structures. The wider intermandibular space in cattle,
      compared with that in horses, made the medial approach and plate placement
      feasible.

PMID- 8150701
TI  - Congenital maldevelopment of the tibia in two calves.
AB  - Two calves were admitted for evaluation of valgus deformity centered at the
      middiaphysis of the right tibia. Each deformity was observed at the time of
      attended, unassisted birth. The limbs were stable and the calves were ambulatory.
      Radiography revealed a thick lateral cortex and radiating trabecular bone
      pattern. The valgus deformities (75 degrees and 45 degrees) were treated by
      corrective osteotomy. One of the cows was bred and carried a clinically normal
      fetus to near term before dying of undetermined causes. The angular limb
      deformities appeared to be attributable to in utero bending stress and bone
      remodeling early in gestation.

PMID- 8150702
TI  - Adenovirus-associated pneumonia and hepatitis in four llamas.
AB  - This report focuses on the diagnostic laboratory and necropsy findings in 4
      llamas with adenovirus-associated hepatitis or pneumonia. In the 2 young llamas,
      clinical illness was characterized by chronic respiratory tract disease. In the 2
      adult llamas, clinical illness was characterized by neurologic signs and a
      history of respiratory tract disease. Histologic examination, electron
      microscopy, virus isolation, and fluorescent antibody results indicated that
      adenovirus infection was associated with disease in all 4 llamas.

PMID- 8150703
TI  - Survival of pigeon red blood cells after transfusion into selected raptors.
AB  - Survival time of 51Cr-labeled pigeon RBC transfused into 5 raptors was
      determined. Mean +/- SD estimated RBC survival time was 0.51 +/- 0.19 days. This
      was considerably shorter than estimated survival time of autologous RBC in a Red
      tailed Hawk (estimated survival, 35.1 days) and in a pigeon (estimated survival,
      26.8 days). Estimated survival time after homologous transfusion of RBC from one
      pigeon to another was 7.1 days. Although single heterologous blood transfusions
      have been recommended as a safe and efficacious means of whole blood replacement
      in birds, results of this study suggest that heterologous RBC transfused from
      pigeons to selected raptor species are rapidly destroyed.

PMID- 8150704
TI  - Enterolithiasis in two zebras.
AB  - Enterolithiasis, as a cause of colic, was diagnosed and treated during surgical
      intervention in 2 Grant's zebras (Equus burchelli bohmi). The zebras were part of
      a wild herd in a zoo in the western United States. The clinical signs of
      enterolithiasis in both zebras were similar to those reported for horses.
      Analysis of the enterolith from 1 zebra revealed a composition identical to
      enteroliths that have been analyzed from horses. Three other zebras from this
      herd had enteroliths at necropsy. Enterolithiasis should be considered as a
      differential diagnosis for zebras with low-grade obstructive colic.

PMID- 8150705
TI  - Veterinary sales and purchases of goods and the warranties that affect them.

PMID- 8150706
TI  - A new topoisomerase II inhibitor, BE-22179, produced by a streptomycete. I.
      Producing strain, fermentation, isolation and biological activity.
AB  - A new topoisomerase II inhibitor, designated BE-22179, was isolated from the
      culture broth of Streptomyces sp. A22179, which resembles "Streptomyces
      gangtokensis". The inhibitor was extracted from the mycelial cake of the culture
      broth with organic solvent and successively purified by silica gel
      chromatography. BE-22179 inhibited topoisomerase II strongly but not
      topoisomerase I and showed potent antitumor activity against various tumor cell
      lines both in vitro and in vivo.

PMID- 8150707
TI  - 3-Alkanoyl-5-hydroxymethyl tetronic acid homologues and resistomycin: new
      inhibitors of HIV-1 protease. I. Fermentation, isolation and biological activity.
AB  - In the course of a screening program for HIV-1 protease inhibiting activity, six
      new homologues of 3-alkanoyl-5-hydroxymethyl tetronic acids (1 approximately 6)
      and the known natural product resistomycin (7) were isolated from cultures of the
      Actinomycete strain DSM 7357. The substituted tetronic acids belong to a recently
      described structural class of secondary metabolites. The HIV-1 activity of
      resistomycin (7) has not been reported before.

PMID- 8150708
TI  - 3-Alkanoyl-5-hydroxymethyl tetronic acid homologues: new inhibitors of HIV-1
      protease. II. Structure determination.

PMID- 8150709
TI  - Pyripyropenes, novel inhibitors of acyl-CoA:cholesterol acyltransferase produced
      by Aspergillus fumigatus. I. Production, isolation, and biological properties.
AB  - Aspergillus fumigatus FO-1289, a soil isolate, was found to produce a series of
      novel inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Four active
      compounds, named pyripyropenes A, B, C and D, were isolated from the fermentation
      broth of the producing strain by solvent extraction, silica gel column
      chromatography, ODS column chromatography and preparative HPLC. Pyripyropenes A,
      B, C and D show very potent ACAT inhibitory activity in an enzyme assay system
      using rat liver microsomes with IC50 values of 58, 117, 53 and 268 nM,
      respectively.

PMID- 8150710
TI  - Pyripyropenes, novel inhibitors of acyl-CoA:cholesterol acyltransferase produced
      by Aspergillus fumigatus. II. Structure elucidation of pyripyropenes A, B, C and
      D.
AB  - The structures of pyripyropenes A, B, C and D, novel acyl-CoA:cholesterol
      acyltransferase (ACAT) inhibitors, were determined mainly by spectroscopic
      studies including various NMR measurements. Pyripyropenes have a common structure
      which consists of pyridine, alpha-pyrone and sesquiterpene moieties. One of the
      three O-acetyl residues in the sesquiterpene moiety of pyripyropene A is replaced
      with an O-propionyl residue in pyripyropenes B, C and D.

PMID- 8150711
TI  - Gypsetin, a new inhibitor of acyl-CoA:cholesterol acyltransferase produced by
      Nannizzia gypsea var. incurvata IFO 9228. I. Fermentation, isolation, physico
      chemical properties and biological activity.
AB  - A novel inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated
      gypsetin, was isolated from the cultured broth of Nannizzia gypsea var. incurvata
      IFO 9228 by solvent extraction, silica gel chromatography and crystallization.
      Gypsetin inhibited rat liver microsomal ACAT activity competitively with respect
      to the substrate oleoyl-CoA with an apparent Ki value of 5.5 microM. In cultured
      macrophage J774 cells incubated with oxidized low density lipoprotein, gypsetin
      inhibited cholesteryl ester formation from [14C]oleate by 50% at a concentration
      of 0.65 microM without affecting cell surface binding, uptake and degradation of
      the lipoprotein.

PMID- 8150712
TI  - Gypsetin, a new inhibitor of acyl-CoA: cholesterol acyltransferase produced by
      Nannizzia gypsea var. incurvata IFO 9228. II. Structure determination.
AB  - The elucidation of the structure of gypsetin, a new inhibitor of acyl-CoA:
      cholesterol acyltransferase, is described in this paper. By spectroscopic and X
      ray crystallographic analyses, the structure of gypsetin has been determined to
      be 8a,16a-dihydroxy-5a,13a-bis[1,1-dimethylallyl]-[1]benzazolidine [3'''
      2''':4'',5'']azolidino[1'',2'':4',5'][1,4]perhydrodiazin[1', 2':1,
      5]azolidino[2,3-b]-[1]benzazolidine-7,15-dione.

PMID- 8150713
TI  - Application of the random amplified polymorphic DNA using the polymerase chain
      reaction for efficient elimination of duplicate strains in microbial screening.
      I. Fungi.
AB  - For efficient fungal strain selection in microbial screening, we applied the
      random amplified polymorphic DNA (RAPD) method using the polymerase chain
      reaction (PCR). In order to evaluate this system, the genus Trichoderma was
      employed, because its species are difficult to distinguish from each other. We
      selected an appropriate oligonucleotide decamer, R28 (5'-ATGGATCCGC), determined
      the optimal cycles of PCR as 30 cycles, simplified the template preparation
      method, and determined optimal concentrations of the template and Taq DNA
      polymerase. We then examined 74 closely related strains of Trichoderma. The
      electrophoretic band patterns of the PCR products were compared. According to the
      statistical analysis with the phylogenetic analysis using parsimony (PAUP), the
      results were consistent with the morphological, physiological and ecological data
      on these strains. Therefore, we conclude that RAPD is a simple, efficient and
      reliable method for the selection of fungal strains employed in screening.

PMID- 8150714
TI  - Application of the random amplified polymorphic DNA using the polymerase chain
      reaction for efficient elimination of duplicate strains in microbial screening.
      II. Actinomycetes.
AB  - We evaluated the random amplified polymorphic DNA (RAPD) method using
      Streptomyces lavendulae and Streptomyces virginiae strains to eliminate duplicate
      actinomycete strains in our microbial screening program. The RAPD data were
      compared with phenotypic characteristics, DNA relatedness, HPLC analysis of
      metabolites and low-frequency restriction fragment analysis by pulsed-field gel
      electrophoresis. These results were consistent with each other. Therefore, we
      conclude that RAPD is a simple, efficient, and reliable method for the selection
      of actinomycete strains.

PMID- 8150715
TI  - Application of the random amplified polymorphic DNA using the polymerase chain
      reaction for efficient elimination of duplicate strains in microbial screening.
      III. Bacteria.
AB  - Random amplified polymorphic DNA (RAPD) analysis was evaluated for the selection
      and elimination of bacterial strains used in microbial screening. For this pilot
      study we used eight bacterial strains producing fragin and two Pseudomonas fragi
      strains, which are often isolated during the screening. A dendrogram constructed
      by the statistical analysis using parsimony, PAUP, based on the band patterns of
      RAPD with primer R28 was in good correlation with the results of DNA-DNA
      hybridization, HPLC analysis of metabolites, and conventional morphological and
      physiological characterization. RAPD was also applicable to a wide range of
      bacteria. This rapid selection system by RAPD was a very useful tool for
      excluding similar bacterial isolates encountered during screening.

PMID- 8150716
TI  - Isolation, structural identification and biological activity of two metabolites
      produced by Penicillium olsonii Bainier and Sartory.
AB  - From the culture broth of a fungus, two metabolites have been isolated: bis(2
      ethylhexyl)phthalate (DEHP) precedently isolated from Streptomyces sp. and 2-(4
      hydroxyphenyl)-2-oxoacetaldehyde oxime (PHBA) here reported as a natural compound
      in the (E)-s-cis configuration. The producing organism was identified as a strain
      of Penicillium olsonii. Culture growth and chemical identification are discussed
      in the present work.

PMID- 8150717
TI  - Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria
      sinclairii metabolite.
AB  - A potent immunosuppressive activity was found in the culture broth of the fungus
      Isaria sinclairii (ATCC 24400). The metabolite, ISP-I ((2S,3R,4R)-(E)-2-amino-3,4
      dihydroxy-2- hydroxymethyl-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin)
      suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte
      reaction, but had no effect on the growth of human tumor cell lines. It also
      suppressed the appearance of plaque-forming cells in response to sheep red blood
      cells and the generation of allo-reactive cytotoxic T lymphocytes in mice after
      intraperitoneal or oral administration. The metabolite was 10- to 100-fold more
      potent than cyclosporin A as an immunosuppressive agent of the immune response in
      vitro and in vivo, and appears to be a candidate for clinical application as a
      powerful immunosuppressant.

PMID- 8150718
TI  - Fungal metabolites. Part 12. Potent immunosuppressant, 14-deoxomyriocin,
      (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyleicos-6-enoic acid and
      structure-activity relationships of myriocin derivatives.
AB  - In order to investigate the structure-activity relationships, fourteen
      derivatives of myriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyl-14
      oxoeicos- 6-enoic acid) were prepared and examined for immunosuppressive activity
      on mouse allogeneic mixed lymphocyte reaction in vitro. Among them, 14
      deoxomyriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyleicos-6-enoic
      acid) was the most potent. It also suppressed the generation of allo-reactive
      cytotoxic T lymphocytes in mice upon intraperitoneal administration, with a
      potency 10-fold greater than that of myriocin.

PMID- 8150719
TI  - Modification of glycopeptide antibiotic eremomycin by the action of alkyl halides
      and study on antibacterial activity of the compounds obtained.
AB  - Alkylation of glycopeptide antibiotic eremomycin by the action of different alkyl
      halides leads, depending on the structure of alkyl halides used, to eremomycin
      derivatives of six types; alkylated at the N-terminus, quaternary compounds at
      the N-terminus, eremomycin esters, esters of eremocycin alkylated at the N
      terminus, esters of eremomycin quaternised at the N-terminus, esters of
      eremomycin alkylated both at the N-terminus and at the aminogroup of disaccharide
      branch. Five compounds demonstrated high antibacterial activity in vitro, N
      allyleremomycin and methyl ester of N,N-dimethyleremomycin being at least as good
      as the parent eremomycin.

PMID- 8150720
TI  - Milbemycin derivatives: modification at the C-5 position.
AB  - Protection of the hydroxyl group at the C-5 position of milbemycin A4 and D was
      carried out to investigate the influence of the C-5 hydroxyl group on the
      anthelmintic potency of these derivatives. Moreover, the hydroxyl group was
      converted into amide groups as bioisosters. Biological activities of these
      derivatives were measured against Nippostrongylus brasiliensis in vitro, and
      minimal concentrations which induce 100% immotility in worms were determined for
      each derivative. Biological testing revealed that the hydroxyl group at C-5 is a
      structural requirement for retaining anthelmintic activity.

PMID- 8150721
TI  - Synthesis of trehazolin beta-anomer.
AB  - Synthesis of trehazolin beta-anomer (3) from a D-glucose derived azido alcohol
      (4), was accomplished. 2-Chloro-1-methylpyridinium iodide was used in place of 2
      chloro-3-ethylbenzoxazolium tetrafluoroborate as a means of preventing
      concomitant anomerization. Evaluation of compound (3) reveals that the
      stereochemistry of the anomeric position is significant for generation of
      inhibitory activities towards trehalases.

PMID- 8150722
TI  - Production of additional squalestatin analogues by directed biosynthesis.

PMID- 8150723
TI  - 16-membered lactone compounds from izenamicins-producing microorganism.

PMID- 8150725
TI  - Magnesidin A, a component of marine antibiotic magnesidin, produced by Vibrio
      gazogenes ATCC29988.

PMID- 8150724
TI  - Novel C-3 cyclic ether cephalosporins and their orally absorbed prodrug esters.

PMID- 8150726
TI  - Synthesis and biological evaluation of neopyrrolomycin analogs.

PMID- 8150727
TI  - Modelling the malleus vibration as a rigid body motion with one rotational and
      one translational degree of freedom.
AB  - Vibration of a set of points distributed along the manubrium of cat was measured
      with a heterodyne interferometer in response to sinusoidal acoustic signals. The
      observed motion did not fit pure rotation of the malleus around a fixed axis
      coinciding with the anterior mallar and posterior incudal ligament as is
      classically assumed. As a first approximation a model of motion consisting of a
      rotational and a translational component was used. At low frequencies the
      rotation is mostly predominant, but the situation may be entirely reversed at mid
      and high frequencies. The presence of a translation besides rotation was also
      found at some frequencies in the motion of the human malleus.

PMID- 8150728
TI  - Pigment-dependent differences in the stria vascularis of albino and pigmented
      guinea pigs and rats.
AB  - Functional models of the stria vascularis (SV) have ascribed roles for the
      marginal and basal cells, but not for the intermediate cells, which remain poorly
      understood. Intermediate cells have been identified as melanocytes, which produce
      melanin in most pigmented animals including humans. The relationship of melanin
      to intermediate cell function may be addressed through comparisons with the
      albino inner ear. Albinos have a normal distribution of melanocytes that are
      unable to synthesize melanin pigment. In the present study, the SV was compared
      between albino and pigmented littermates in both the guinea pig and the rat.
      Photomicrographic montages of the SV were analyzed from each of 7 cochlear
      regions in the guinea pig and 5 regions in the rat. Stereological procedures were
      used to determine the volume density (Vv) for each of the three main cell types
      in the stria, the surface density (Sv) of the marginal cells, and to derive
      estimates of absolute cell volume and surface area. In the guinea pig,
      comparisons between pigment groups showed that marginal cell Vv was larger across
      cochlear turns in the albinos, while intermediate cell Vv was smaller.
      Intermediate cell cytoplasmic and total cell volumes were smaller in the albino
      guinea pigs; however, marginal cell Sv and absolute area were larger. In the rat,
      intermediate cell Vv was alos smaller across cochlear turns in the albinos.
      Similarly, intermediate cell cytoplasmic and total cell volumes were smaller in
      the albinos, while marginal cell total surface area per radial cross-section of
      the SV was larger. These results demonstrate that amelanotic melanocytes occupy
      significantly less volume than do pigmented melanocytes, and suggest that melanin
      may influence the structure and function of the SV.

PMID- 8150729
TI  - Plastic changes in ipsi-contralateral differences of auditory cortex and inferior
      colliculus evoked potentials after injury to one ear in the adult guinea pig.
AB  - In normal adult guinea pigs, evoked potentials recorded at the ipsilateral
      auditory cortex to monaural high-frequency acoustic stimuli present higher
      thresholds and lower amplitudes than at the contralateral cortex; in the inferior
      colliculus, such ipsi-contralateral differences (ICDs) are smaller than in the
      auditory cortex. Changes in the ICDs were studied after opposite ear injury.
      Following quasi-complete hair cell destruction induced by sisomicin injection
      into the contralateral inner ear, threshold ICDs almost disappeared after about
      two to six days and ipsilateral amplitudes progressively increased in two to
      three weeks. The occurrence of ICDs at higher auditory centers revealed in this
      study, indicates peculiar processing of high frequency stimuli in normal guinea
      pigs. The alteration of ICDs after opposite ear impairment provides a new
      possibility to study the auditory plasticity in adult animals.

PMID- 8150730
TI  - Differences of inner and outer hair cells in the organ of Corti of the guinea pig
      in respect to the cellular content of precipitable calcium.
AB  - Differences between inner and outer hair cells in the cellular content of
      precipitable calcium were detected using a potassium pyroantimonate precipitation
      method and the electron spectroscopic imaging (ESI-) technique. The cytoplasm of
      the inner hair cells was scattered with a high number of calcium precipitates in
      all analysed animals, but only a few reaction products could be identified in the
      cytoplasm of the outer hair cells in all analyzed specimens. Even the well
      developed system of the subsurface fenestrated cisternae in the outer hair cells
      was nearly empty of calcium precipitates. A relatively high amount of reaction
      products could be identified in the nuclei of both types of nerve endings of the
      receptor cells. Significant differences regarding the content of precipitable
      calcium were found in the different types of nerve endings, which come into
      contact with the basal parts of both receptor cells. The observed differences in
      the content of precipitable calcium between the two types of hair cells are
      discussed with respect to their probable different roles in signal transduction
      processes.

PMID- 8150731
TI  - Purkinje-like cells in rat cochlear nucleus.
AB  - A unique class of cells, strongly immunopositive for anti-calbindin D-28 kDa was
      observed in and near the cochlear nucleus of young adult, male Sprague-Dawley
      rats. These cells are present in small numbers which are highly variable across
      animals and inconstant in position. They are preferentially located in the dorsal
      cochlear nucleus, with occasional examples being present in the ventral cochlear
      nucleus, as well as in adjacent brainstem locations. They have been referred to
      in other studies as displaced Purkinje cells or 'Purkinje cell-like cells', and
      are here designated 'Purkinje-like cells' (PLCs). PLCs have relatively large cell
      bodies, with thick, heavily spined dendrites, and are typically situated in an
      immediately subpial position. The dendritic arborization extends into the
      interior of the nucleus, away from the pial surface, a trajectory opposite in
      direction to that of the cerebellar Purkinje cells. The intense immunoreactivity
      exhibited by PLC somata and dendrites when treated with antiserum directed
      against calbindin is equivalent to that of cerebellar Purkinje cells, and
      markedly stronger than that of most other cell populations of the cochlear
      nucleus. However, in tissue treated with anti-parvalbumin, which also strongly
      labels cerebellar Purkinje cell somata and dendrites, PLC labeling, when present,
      is relatively weak, limited to the cell bodies and only the base of the dendrites
      of PLCs, indicating non-equivalence of the two cell types. In addition, the
      intensity of calbindin immunostaining in the PLCs appears to be more sensitive to
      glutaraldehyde in any of the fixative solutions than that seen in cerebellar
      Purkinje cells in the same sections. Of the cell types of the cochlear nucleus,
      the cartwheel cells would appear to be the most similar to the PLCs on
      morphological and immunocytochemical grounds. However, the subpial position and
      average somal dimensions of the PLCs, as well as the relatively modest
      immunoreactivity of the cartwheel cells for calbindin, rather clearly
      differentiate the PLCs from this class of neurons. The results of the present
      study suggest that the PLCs of the cochlear nucleus, although they may arise
      developmentally as ectopic cerebellar Purkinje cells and maintain certain
      Purkinje cell characteristics, represent a distinct neuronal cell type in the
      adult rat cochlear nucleus, exhibiting incomplete overlap of fixation,
      immunocytochemical and morphological characteristics with both cartwheel cells of
      the cochlear nucleus and cerebellar Purkinje cells.

PMID- 8150732
TI  - Spontaneous otoacoustic emissions in the bobtail lizard. II: Interactions with
      external tones.
AB  - The response of spontaneous otoacoustic emissions to the presentation of external
      tones was studied in the Australian bobtail lizard. Three basic types of effects
      were observed: suppression (a reduction in the emission's amplitude),
      facilitation (an increase in the emission's amplitude) and frequency shifting.
      The suppressive effect was highly frequency selective. Iso-suppression tuning
      curves resembled the rate-threshold tuning curves of the high-frequency
      population of VIIIth nerve fibres in this species. The frequency with the lowest
      threshold for suppression corresponded, on average, to the emission's own
      frequency and did not show any systematic deviation from it. Facilitation of
      between 2 and 10 dB occurred, but only in response to frequencies within certain
      narrow ranges, and at sound pressure levels below those that suppressed. The most
      commonly-observed facilitation range lay between 0.2 and 0.6 octaves above the
      emission's own frequency and coincided in frequency with a characteristic notch
      in the iso-suppression tuning curve. In the same narrow frequency range, the
      input/output functions of amplitude suppression always showed a pronounced
      increase in slope. The emissions moved their own frequency away from that of an
      external tone. The observed shifts were comparatively large (up to -330 Hz) and
      were more pronounced in the downward direction.

PMID- 8150733
TI  - Spontaneous otoacoustic emissions in the bobtail lizard. III: Temperature
      effects.
AB  - Spontaneous otoacoustic emissions (SOAE) in the ear canal of the Australian
      bobtail lizard are temperature sensitive. They shift their frequency up with an
      increase in temperature, an effect that is fully reversible. The degree of shift
      is dependent not only on the center frequency of the SOAE (lower-frequency SOAE
      show a smaller shift) but also on the temperature range in question. Rates of
      change of frequency are 0.014 to 0.04 oct/degrees C at 30 degrees C, and twice
      that at 22 degrees C. There was no strong and consistent effect of temperature on
      SOAE amplitudes. The above findings are very similar to those on the effect of
      temperature on SOAE of frogs and mammals. Suppression tuning curves of SOAE
      shifted with temperature, the largest effects being near the center frequency in
      the tuning-curve's tip region.

PMID- 8150734
TI  - Distribution of actin in developing outer hair cells in the gerbil.
AB  - During the two weeks following the onset of cochlear function in the gerbil,
      active cochlear processes appear to mature. The active cochlear processes likely
      involve outer hair cells with their specialized lateral wall structures,
      including the subsurface cisternae and associated cytoskeletal elements. We have
      previously demonstrated that the subsurface cisternae mature gradually during the
      time that active cochlear processes mature in the gerbil. In the study reported
      here, we used postembedding immunocytochemical electron microscopy to investigate
      whether actin labelling associated with the cortical cytoskeleton of the gerbil
      outer hair cell increased concomitantly. In contrast to the gradual development
      of the subsurface cisternae, actin labelling in the region of the cortical
      cytoskeleton significantly increased during the onset of cochlear function and
      maintained this level during the time that active cochlear processes mature.
      Thus, it appears that increased actin adjacent to the lateral plasma membrane of
      the outer hair cell is related to the onset of cochlear function rather than to
      the maturation of active cochlear processes.

PMID- 8150735
TI  - Toluene exposure affects the functional activity of the outer hair cells.
AB  - Rats were exposed to toluene by inhalation (1400 ppm, 16 h/d, 8 days) and the
      auditory brainstem response (ABR) and distortion product otoacoustic emissions
      (DPOEs) were used as measures of the auditory sensitivity. These measurements
      were made before the exposure to toluene, 3 and 5 days after the start of the
      exposure and 4 days after the end of the exposure. To quantify the repeated DPOE
      data the area under the curve of the DPOE amplitudes versus the stimuli levels
      was calculated and used for statistical analysis. Results demonstrate that 3 days
      of toluene exposure tended to lower DPOE amplitudes and elevate ABR thresholds.
      Similarly after 5 days of exposure significantly lower DPOE amplitudes were
      observed at most frequencies along with elevated ABR thresholds. At 4 days post
      exposure DPOE amplitudes were greatly diminished at all frequencies and the ABR
      thresholds were raised by about 40 dB between 1.6 and 20 kHz. These results show
      a parallel shift between ABR thresholds and DPOE amplitudes during toluene
      exposure. Furthermore, the results from the DPOE measurements indicate that
      mainly the outer hair cells are adversely affected by toluene exposure.

PMID- 8150736
TI  - Internally-generated sound stimulates cochlear nucleus units.
AB  - The body generates many physiological sounds. One of the most prominent is that
      produced by the blood flowing inside the vessels with each heart beat. On the
      other hand, the cochlea is a very sensitive receptor with a low threshold. Given
      the anatomical close proximity of the carotid artery and other vessels to the
      inner ear, the possibility of its being stimulated is very high. Cochlear nucleus
      spontaneous as well sound-responding auditory units were studied. A close
      relationship between the heart beat, that is the blood flow, and the cochlear
      nucleus firing was demonstrated, in anesthetized and awake guinea-pigs. Temporary
      mechanical interruption of the blood flow through the ipsilateral carotid artery
      abolished firing increments at the cochlear nucleus time-locked to the heart
      beat. We conclude that one component of the so called 'spontaneous' firing in the
      auditory system is actually evoked activity due to normal body-generated sounds
      or noises.

PMID- 8150737
TI  - Population responses to multifrequency sounds in the cat auditory cortex: one-
      and two-parameter families of sounds.
AB  - Population responses to multi-frequency sounds were recorded in primary auditory
      cortex of anesthetized cats. The sounds consisted of single-tone stimuli; two
      tone stimuli; and nine-tone stimuli, with the tones evenly spaced on a linear
      frequency scale. The stimuli were presented through a sealed, calibrated sound
      delivery system. Single units, cluster activity (CA) and the short-time mean
      absolute value of the envelope of the neural signal (MABS) were recorded
      extracellularly from six microelectrodes simultaneously. The CA and MABS were
      interpreted as measures of the activity of large populations of neurons, in
      contrast with the single unit activity which is presumably recorded from single
      neurons. The responses of the MABS signal to simple stimuli were generally
      similar to those of the CA, but were more stable statistically. Thus, the MABS is
      better suited for studying the activity of populations of neurons. The responses
      to tones near the best frequency were strongly influenced by a second tone, even
      when the second tone was outside the single-tone response area. These influences
      could be both facilitatory and suppressory. They could not be predicted from the
      responses to single tones. The responses to the nine-tone stimuli could be
      explained qualitatively by the responses to the two-tone stimuli. It is concluded
      that the population responses in primary auditory cortex are shaped by the
      contributions of the individual frequencies appearing in the stimulus and by the
      interactions between pairs of frequencies. Interactions between stimulus
      components are therefore a necessary component of any attempt to explain the
      processing of complex sounds in the auditory cortex. They may play a role in a
      global representation of the stimulus spectrum in the primary auditory cortex.
      The presence of higher-order interactions cannot be excluded by the results
      presented here.

PMID- 8150738
TI  - Population responses to multifrequency sounds in the cat auditory cortex: four
      tone complexes.
AB  - Population responses to two-tone and four-tone sounds were recorded in primary
      auditory cortex of anesthetized cats. The stimuli were delivered through a
      sealed, calibrated sound delivery system. The envelope of the neural signal
      (short time mean absolute value, MABS) was recorded extracellularly from six
      microelectrodes simultaneously. A new method was developed to describe the
      responses to the four-tone complexes. The responses were represented as sums of
      contributions of different orders. The first order contributions described the
      effect of the single frequencies appearing in the stimulus. The second order
      contributions described the modulatory effect of the pairs of frequencies. Higher
      order contributions could in principle be computed. This paper concentrates on
      the mean onset responses. The extent to which the first and second order
      contributions described the onset responses was assessed in two ways. First, the
      actual responses to two-tone stimuli were compared with those predicted using the
      contributions computed from the four-tone stimuli. Second, the residual variance
      in the responses, after the subtraction of the first and second order
      contributions, was computed and compared with the variability in the responses to
      repetitions of the same stimulus. The first type of analysis showed good
      quantitative agreement between the predicted and the measured two-tone responses.
      The second type of analysis showed that the first and second order contributions
      were often sufficient to predict the responses to four-tone stimuli up to the
      level of the variability in the responses to repetitions of a single stimulus. In
      conjunction with the results of the companion paper (Nelken et al., 1994a) it is
      concluded that the onset responses to multifrequency sounds are shaped mainly by
      the single frequency content of the sound and by two-tone interactions, and that
      higher order interactions contribute much less to the responses. It follows that
      single-tone effects and two-tone interactions are necessary and sufficient to
      explain the mean population onset responses to the four-tone stimuli. More
      information can be coded in the temporal evolution of the responses.

PMID- 8150739
TI  - Protection from noise-induced hearing loss by prior exposure to a nontraumatic
      stimulus: role of the middle ear muscles.
AB  - Recent evidence suggests that prior exposure to a moderate-level acoustic
      stimulus can reduce damage due to later exposure to the same stimulus at high
      intensity [Canlon et al., Hear. Res. 34, 197-200 (1988)]. To test the role of the
      middle ear muscles (MEMs) in this phenomenon, Mongolian gerbils were conditioned
      by exposure to a two-octave band of noise (1414-5656 Hz) at 81 dB SPL for 3
      weeks. Either immediately afterward, or following a one week rest period, they
      were exposed to the same stimulus at 110 dB SPL for one hour. The ABR thresholds
      of these animals were compared to those seen in animals exposed at 110 dB SPL
      without conditioning. The MEMs of one ear in each subject were cut, to determine
      their role in any noise trauma protection effects. In the unoperated ears,
      conditioning without a recovery period did not alter the effects of the 110 dB
      stimulus. Conditioning followed by a one week recovery period reduced both
      temporary (TTS) and permanent (PTS) threshold shift. MEM section had no effect on
      either TTS or PTS in unconditioned subjects, and did not alter the reduction in
      TTS or PTS seen with conditioning. It is concluded that the noise trauma
      resistance provided by acoustic conditioning is not mediated by the MEMs.

PMID- 8150740
TI  - In search of the best stimulus: an optimization procedure for finding efficient
      stimuli in the cat auditory cortex.
AB  - Units in the auditory cortex of cats respond to a large variety of stimuli: pure
      tones, AM- and FM-modulated signals, clicks, wideband noise, natural sounds, and
      more. However, no single family of sounds was found to be optimal (in the sense
      that oriented lines are optimal in the visual cortex). The search for optimal
      complex sounds is hard because of the high dimensionality of the space of
      interesting sounds. In an effort to overcome this problem, an automatic search
      procedure for finding efficient stimuli in high-dimensional sound spaces was
      developed. This procedure chooses the stimuli to be presented according to the
      responses to past stimuli, trying to increase the strength of the response. The
      results of applying this method to recordings of population activity in the
      primary auditory cortex of cats are described. The search was applied to single
      tones, two-tone stimuli, four-tone stimuli and to a two-dimensional subset of
      nine-tone stimuli, parametrized by the center frequency and the fixed difference
      between adjacent frequencies. The method was able to find efficient stimuli, and
      its performance improved with the dimension of the sound spaces. Efficient
      stimuli, found in different optimization runs using population activity recorded
      from the same electrode, often shared similar frequencies and pairs of
      frequencies, and tended to evoke similar levels of activity. This result
      indicates that a global analysis of the location of spectral peaks is performed
      at the level of the auditory cortex.

PMID- 8150742
TI  - Stimulus-onset dominance in the perception of binaural information.
AB  - With dichotic signals presented by headphone, stimulus-onset dominance (the
      'precedence effect') was investigated for various types of binaural-processing
      based percepts. The following three dichotic cues were considered: (1) inter
      aural time delay (IATD, underlying the lateralization of the sound image), (2)
      inter-aural level difference (IALD, also underlying lateralization), and (3)
      inter-aural cross correlation (IACC, underlying the spaciousness of the sound
      image in terms of broadness/compactness). For all three cases, the degree of
      stimulus-onset dominance is estimated by one and the same experimental paradigm,
      which is essentially the same as used by Aoki and Houtgast [Hear. Res. 59, 25-30
      (1992)]: When subdividing a brief stimulus in two parts of equal duration, a
      leading and a trailing part, in which the dichotic cue has opposite values, the
      over-all sensation is found to be dominated by the cue in the leading part. This
      dominance can be compensated by shortening the leading part (while keeping total
      signal duration constant), providing a quantitative measure for the onset
      dominance. The signals were octave-band filtered noise (center frequencies 500 or
      2000 Hz) or 7-kHz low-pass filtered noise, and total signal duration was 5, 10,
      20 or 40 ms. The results obtained for the four signal durations have been
      converted to a weighting function, representing the perceptual weight of the
      dichotic information as a function of time-after-signal-onset.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8150741
TI  - A characteristics protein highly expressed in guinea pig inner ear, defined by
      monoclonal antibody WH-1.
AB  - A new monoclonal antibody (termed WH-1; isotype IgG2b) was established using a
      homogenate of dissected guinea pig cochleas (N = 60) as immunogen. Western
      blotting and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      identified the WH-1 antigen as a protein or glycoprotein with M(r) approximately
      40 kDa. Immunoperoxidase treatment of histologic cryosections of guinea pig
      cochlea, followed by light microscopic examination, revealed strong positive
      staining at three sites: (i) parts of Hensen's stripe, marginal band, covering
      net, and Kimura's membrane (within the tectorial membrane [TM]); (ii) Deiters'
      cells, pillar cells, Hensen's cells, and stereocilia of outer hair cells (within
      the organ of Corti); (iii) interdental cells, inner and outer sulcus cells,
      Reissner's membrane, and surface membrane of stria vascularis epithelium. Similar
      staining patterns were observed for cryosections of rat and mouse cochleas. Only
      a trace quantity of cross-reacting protein was detectable in brainstem. The
      protein was not detectable in tongue extract by Western blotting. However,
      sections of brainstem and tongue did show positive immunohistological staining
      with WH-1. Localization of WH-1 antigen was further examined by electron
      microscopy. WH-1 positivity on outer hair cell stereocilia, certain sites on the
      TM, interdental cell surface, Reissner's membrane epithelia, and inner and outer
      sulcus cells was confirmed. WH-1 antigen was not detected on inner hair cell
      stereocilia by light or electron microscopy. The localization of WH-1 antigen on
      outer hair cell stereocilia and TM suggests that it may play some role in
      adhesion between these structures.

PMID- 8150743
TI  - Postnatal changes in cochlear polyamine metabolism in the rat.
AB  - Ornithine decarboxylase (ODC), the initial enzyme in the polyamine biosynthetic
      pathway, is increased in the developing rat cochlea, suggesting that polyamine
      biosynthesis is important in cochlear development. Although cochlear polyamines
      have been detected in adult rats, they have not been identified in developing
      rats. We quantified polyamines in the developing and mature rat cochlea and
      further characterized ODC in the early postnatal period. Putrescine and
      spermidine in combined tissues of the organ of Corti and lateral wall of the
      cochlea were highest during the first 10 postnatal days, then declined to adult
      levels shortly thereafter. Spermine demonstrated a similar developmental trend. A
      high spermidine to spermine ratio was noted during this period as was rapidly
      increasing ODC activity. A high spermidine/spermine ratio was also noted in the
      cochlear nerve of developing and mature rats, suggesting that spermidine may be
      necessary for function and maintenance of the nerve. This is the first report of
      polyamines in the developing rat cochlea. The period of increased polyamine
      synthesis coincides with the critical period for ototoxicity induced by alpha
      difluoromethylornithine, a specific ODC inhibitor, and the period of rapid
      cochlear development.

PMID- 8150744
TI  - Development of gerbil outer hair cells after the onset of cochlear function: an
      ultrastructural study.
AB  - It has recently been proposed that elements which contribute to active cochlear
      processes develop at the same time (between postnatal day (PND) 12 and 21) as the
      shift of the place code in the developing gerbil cochlea. Since outer hair cells
      (OHCs) have been implicated in these processes, we have hypothesized that
      developing OHCs will exhibit changes in anatomical features that contribute to
      cochlear maturation. Our results demonstrate that the ultrastructural
      characteristics of OHCs change after the onset of hearing (PND 12), during the
      time that cochlear nonlinearities are being established (PND 12-21). Differences
      are primarily associated with the distribution of cytoplasmic organelles. The
      subsurface cisternae (SSC), which are thought to be related to the mechanical
      support of the outer hair cell, to cell motility, and therefore to cochlear
      mechanics, are present at PND 10 but remain immature, with cisternal layers added
      during the preweanling period. In immature OHCs, more mitochondria are centrally
      located than in mature OHCs. During development mitochondria come to form a
      continuous row near the innermost leaflet of the SSC. These ultrastructural
      features undergo rapid change during the maturation of peripheral auditory
      function.

PMID- 8150745
TI  - N-myc expression in the embryonic cochlea of the mouse.
AB  - N-myc expression in the mouse embryo was examined during the late cochlear
      organogenesis. Tissue distribution of N-myc expression was histologically
      analyzed by in situ hybridization of the transcript in the cochlea between 15 and
      18 days of gestation. At 15 days of gestation, N-myc expression was found very
      conspicuous in nervous structure of the cochlea such as the auditory nerve and
      the spiral ganglion. Moreover, N-myc was also present in the Kollikers organ and
      in the epithelium surrounding the cochlear canal. A few days later, N-myc
      expression was still clearly present in the Kollikers organ but less so in
      nervous structures. This study shows that cochlear tissues derived from the otic
      placode present a significant level of N-myc transcript during late
      embryogenesis. N-myc expression seems to be related to cell differentiation in
      the inner ear.

PMID- 8150746
TI  - Otoacoustic emissions from the cochlea of the 'constant frequency' bats,
      Pteronotus parnellii and Rhinolophus rouxi.
AB  - During stimulation with continuous pure tones, the cochlea of each individual of
      the mustached bat, Pteronotus parnellii, produces a strong evoked stimulus
      frequency otoacoustic emission (SFOAE) at about 62 kHz. The SFOAEs were on
      average 480 Hz above the dominant constant frequency component of the
      echolocation call (resting frequency, RF). In two out of nine individuals of
      Pteronotus the SFOAEs changed into spontaneous otoacoustic emissions of 25-40 dB
      SPL. In the rufuous horseshoe bat, Rhinolophus rouxi spontaneous emissions were
      not detected and only in two out of seven animals were there weak SFOAEs about
      300 Hz above the RF of 78 kHz. This difference may be due to a stronger damping
      of underlying resonant processes in Rhinolophus (Henson et al., 1985a). Acoustic
      distortion products behaved quite similar in both species. The first lower
      sideband distortion 2f1-f2 was measurable over a wide frequency range between 10
      and 100 kHz. The optimum frequency separation delta f of the two primary tones to
      evoke maximum 2f1-f2 distortion was 0.8 to 5.8 kHz in Pteronotus and 1 to 7 kHz
      in Rhinolophus for frequencies outside the range of the constant frequency
      components of the call. This corresponds to ratios f2/f1 of about 1.03 to 1.2. At
      the frequency of the SFOAE in Pteronotus (480 Hz above the RF) and about 300 Hz
      above the RF in Rhinolophus the optimum delta f decreased sharply to values of 31
      63 Hz in Pteronotus (ratio f2/f1 of 1.0005-1.001), and to 39-590 Hz in
      Rhinolophus (ratio f2/f1 of 1.0005-1.007). In Pteronotus a second minimum of
      delta f was found at about 90 kHz (values of 180-620 Hz, ratios f2/f1 of 1.002
      1.007). In both bat species, the respective minima of delta f are located at or
      close to frequencies where neuronal tuning sharpness is exceptionally high. This
      indicates a mechanical origin of enhanced tuning. After adjusting the frequency
      of f2 to match the optimum delta fs, 2f1-f2 threshold curves were obtained. The
      distortion product threshold approximately parallels neuronal data and is in both
      species characterized by a pronounced insensitivity at the RF followed by a steep
      threshold minimum at frequencies 0.3-3 kHz above the RF. These features may be
      involved in reducing the cochlear response to the call such that the bats are
      able to focus on the Doppler-shifted echos which are slightly higher in frequency
      and thus within the range of the threshold minimum.

PMID- 8150747
TI  - Evidence for a mechanical filter in the cochlea of the 'constant frequency' bats,
      Rhinolophus rouxi and Pteronotus parnellii.
AB  - To investigate the function of basilar membrane (BM) thickenings in the cochlea
      of bats which use constant frequency (CF) echolocation calls, acoustic distortion
      products were measured while placing the primary stimuli f1 and f2 at frequencies
      which are represented in the thickened BM regions. In Rhinolophus, for primary
      stimuli between about 80-100 kHz, pronounced maxima of the level of distortion
      products (2f1-f2, 3f1-2f2, 4f1-3f2) can be measured if the frequency separation
      between the two primary tones is chosen so that the resulting distortion
      frequency matches the dominant CF frequency (resting frequency, RF). The
      distortion maxima extend from the individual RF down to frequencies which are 2-4
      kHz lower. The data indicate that the thickened BM region in the basal halfturn
      of the cochlea strongly oscillates at the bats' RF and slightly below. The
      hearing threshold, however, is at a maximum at the RF (see Kossl 1993).
      Therefore, the RF oscillations are thought to be involved in absorbing the
      respective frequency such that the more apically located frequency place of the
      RF is insensitive and a mechanical notch filter is established. In Pteronotus,
      there are maxima of the level of 2f1-f2 at distortion frequencies around the RF
      of about 61.5 kHz up to the frequency of a strong stimulus-frequency otoacoustic
      emission (SFOAE) which is a few hundred Hz higher. Pronounced distortions in the
      RF range can only be elicited when the stimulus frequencies are between about 62
      to 72 kHz. Similar to the situation in Rhinolophus, this frequency band is
      represented on a stretch of thickened BM.

PMID- 8150748
TI  - TEM analysis of neural terminals on autoradiographically identified regenerated
      hair cells.
AB  - Regenerated tall and short hair cells identified by autoradiography
      ([3H]thymidine) were analyzed for their neural contacts using transmission
      electron microscopy. Ears from mature Coturnix quail (N = 5) exposed to pure tone
      overstimulation (1500 Hz, 115 dB, 12 h) and treated with [3H] thymidine for 10
      days were fixed, embedded, sectioned serially in 100 mu intervals and prepared
      for autoradiography. At fifty percent length along the papilla, alternating semi
      thick (1 micron) and thin (70 nm) sections were taken at 50 microns intervals.
      Semi-thick sections were analyzed at the light microscope level for
      autoradiographic labeling of [3H]thymidine over the hair cell nucleus. When an
      autoradiographically labelled hair cell was identified the corresponding serial
      thin sections were analyzed in the transmission electron microscope. Seven
      autoradiographically labeled hair cells in semi-thin sections were positively
      identified in immediately adjacent thin serial sections. Labeled hair cells were
      morphologically similar to adjacent cells with no label and generally appeared to
      receive similar innervation. Regenerated short hair cells showed large chalice
      shaped, efferent terminals, intermediate hair cells received both afferent and
      efferent innervation and tall hair cells were contacted by two to three afferent
      terminals with synaptic specializations. These results provide conclusive
      evidence of both efferent and afferent synaptic contacts on newly regenerated
      hair cells of all types 10 days following acoustic trauma.

PMID- 8150749
TI  - Partial hearing loss in the macaque following the co-administration of kanamycin
      and ethacrynic acid.
AB  - Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA)
      rapidly produces a profound hearing loss in the cat while maintaining normal
      renal function [Xu et al., Hear. Res. 70, 205-215 (1993)]. In the present paper
      we have applied this deafening procedure to the old world monkey Macaca
      fascicularis (macaque). Following the co-administration of KA and EA, the hearing
      loss in the macaque developed far slower than we observed in the cat. Moreover,
      unlike the cat, there was evidence of a partial recovery in the animal's hearing,
      resulting in a bilaterally symmetrical high frequency hearing loss. The extent of
      this hearing loss was dependent on the dose of the EA administered. Finally, the
      most unexpected result of the present study was the degree of acute
      nephrotoxicity experienced by these animals following the drug administration.
      The sensitivity of this species to renal failure restricted the dose of EA that
      could be safely administered. In conclusion, the co-administration of KA and EA
      cannot reliably produce a profound hearing loss in the macaque. While it can
      produce a dose dependent high frequency hearing loss the animal will also
      experience acute renal failure that requires careful management.

PMID- 8150750
TI  - 3CLT ABR analyses in a human subject with unilateral extirpation of the inferior
      colliculus.
AB  - Reported are the results of analyses of three-channel Lissajous trajectories
      (3CLTs) of the auditory brain stem responses (ABRs) in a human subject in whom a
      focal lesion of the brain stem was caused by stereotactic radiosurgery, the
      'gamma knife'. The surgery caused total destruction of the right inferior
      colliculus. The results, using multiple measures for defining ABR components,
      confirm findings from more conventional 2-channel recordings which, in turn,
      suggested the presence of an intact wave IV but a negligible, if not totally
      absent, wave V with stimulation of the left (contralateral) ear. The results thus
      support theories that wave V is generated by crossed pathways and that wave IV is
      an independent wave generated by the lateral lemniscus. Since magnetic resonance
      imaging suggested no destruction of tissue below the inferior colliculus, the
      findings also support theories of wave V generation at or rostral to the inferior
      colliculus. In practical terms, the results demonstrate the value of multichannel
      recordings of the ABR in component identification and in interpreting ABR
      abnormalities.

PMID- 8150751
TI  - beta-Lactam resistance amongst Enterobacter species.
AB  - Following the introduction of extended-spectrum cephalosporins into clinical use,
      the prevalence of species belonging to the genus Enterobacter has increased
      because of their natural resistance to earlier cephalosporins and their ability
      to develop resistance rapidly to the newer drugs. beta-Lactam resistance in this
      genus is due, for the most part, to the presence of a Bush group 1 chromosomal
      cephalosporinase. This enzyme is normally inducible and resistance to older
      cephalosporins, cephamycins and aminopenicillins results from either the extreme
      lability of the drugs to the enzyme or from their inducer activities. Resistance
      to newer penicillins, cephalosporins and monobactams is attributable to the
      selection of mutants which express large amounts of the enzyme. Such mutants
      arise as the result of a spontaneous mutation in one of the regulatory genes
      responsible for suppressing enzyme expression. Since the enzyme has very high
      affinity for the newer cephalosporins, this, coupled with the slow penetration of
      the drugs into the cell, provides a very efficient mechanism of resistance.
      Recent surveys in the USA and elsewhere have shown that the increased prevalence
      of multi-beta-lactam-resistant strains of enterobacter is due to the increased
      use of the newer cephalosporins. Attempts to prevent these problems include the
      more judicious use of newer beta-lactam antibiotics and the development of
      enhanced-potency cephalosporins which are able to avoid resistance because they
      have lower enzyme affinity and permeate more rapidly into the cell.

PMID- 8150752
TI  - Cefepime: a beta-lactamase-stable extended-spectrum cephalosporin.

PMID- 8150753
TI  - Pharmacokinetics of cefepime: a review.
AB  - The pharmacokinetic profile of cefepime following single and repeated i.v. or im
      administration was evaluated in healthy volunteers (n = 130), volunteers with
      renal failure (n = 42), elderly volunteers (n = 24), and in infected patients (n
      = 10). Following a 30 min iv infusion of between 250 and 2000 mg, the maximum
      plasma concentration (Cmax) and area under the concentration-time curve (AUC)
      increased in proportion to the dose, indicative of linear kinetics. The Cmax
      ranged between 16.3 and 133 mg/L, with corresponding AUC values ranging between
      34 and 263 mg.h/L. The elimination half-life (T1/2) was approximately 2 h and was
      dose-independent. Total clearance (Cltot) for all doses ranged between 122 and
      136 mL/min. Renal clearance (Clren) varied between 96 and 116 mL/min, suggesting
      that cefepime is eliminated mainly by glomerular filtration. No probenecid
      studies have been performed. Urinary excretion was comparable at all dose levels,
      with the parent compound accounting for > 80% of the recovered dose (i.v. or im).
      Following single im doses of between 250 and 2000 mg, absorption was rapid and
      the Tmax was attained in 1-1.6 h. Values for Cmax and AUC increased in a dose
      proportional manner. The T1/2 was approximately 2 h and independent of dose. The
      bioavailability following im administration of 2000 mg was 100%. No accumulation
      following multiple i.v. or im dosing over 10 days was observed. Binding to plasma
      proteins was 16%. The volume of distribution at steady-state (Vdss) varied
      between 18 and 22 L and was dose-independent. The pharmacokinetic profiles of
      cefepime following single and repeated doses suggest that twice-daily
      administration by either the i.v. or im route is adequate to treat most
      infections caused by susceptible bacteria.

PMID- 8150754
TI  - Pharmacokinetics of cefepime in patients with the sepsis syndrome.
AB  - We investigated the pharmacokinetics of cefepime after administration of multiple
      doses to seven patients with the sepsis syndrome. Patients ranged in age from 66
      to 78 years (mean +/- S.D.: 74 +/- 5 years); all fulfilled the criteria of the
      sepsis syndrome and had APACHE-II scores between 14 and 21 (mean +/- S.D.: 17 +/-
      2). Serial blood and urine samples were collected after a minimum of 3 days
      (steady state) of treatment with cefepime 2.0 g bd i.v. Cefepime was assayed by
      HPLC. Data were analysed using non-compartmental methods. The mean +/- S.D.
      creatinine clearance (Clcr) was 55 +/- 8 mL/min. Mean +/- S.D. values for
      selected pharmacokinetic parameters on day 5 were Cmax (94.2 +/- 23.9 mg/L), T1/2
      (3.4 +/- 1.1 h), Vdss (32.6 +/- 17.5 L), and the total clearance Cl(total) (125
      +/- 51 mL/min). Time to peak plasma concentration (Tmax) and area under curve
      (AUC) averaged 0.7 +/- 0.2 h and 305 +/- 115 mg.h/L, respectively. Cefepime
      plasma concentrations were above the MIC90 for Pseudomonas aeruginosa (7 mg/L)
      for approximately 80% of the time and in the case of Enterobacteriaceae (0.5
      mg/L) for 100% of the time. The more prolonged T1/2 in comparison with young
      healthy volunteers (T1/2 = 2.1 h) is consistent with the changes in renal
      function associated with increased age, and is comparable to data obtained in
      healthy elderly subjects (T1/2 = 3.7 h). Cmax, AUC and Cl(tot) were more variable
      than those observed in previous studies and are probably a reflection of the
      clinical conditions under which dosing and sampling occurred.

PMID- 8150755
TI  - Low-dosage cefepime as treatment for serious bacterial infections.
AB  - Since infection develops in significant numbers of hospitalized patients, the
      problem of resistance to third-generation cephalosporins is of increasing
      concern. We evaluated the efficacy of cefepime 1 g bd as treatment for acute,
      moderately severe bacterial infection in 239 hospitalized patients (mean age 60
      years). Of these patients, 204 were evaluated clinically for urinary tract
      infection (UTI) (n = 90), lower respiratory tract infection (LRTI) (n = 70), skin
      and soft tissue infection (S/STI) (n = 12) and bacteraemia which was associated
      with either UTI or LRTI (n = 32) but not included in the previously mentioned UTI
      and LRTI groups. Amongst the pathogens isolated (36 Gram-positive, 150 Gram
      negative), the most predominant species were Escherichia coli in UTI and
      bacteraemia (n = 81), Streptococcus pneumoniae in LRTI and bacteraemia (n = 23),
      Haemophilus influenzae in LRTI (n = 16), Pseudomonas aeruginosa (n = 4) and
      Enterobacter cloacae (n = 2) in S/STI. The mean duration of treatment was 8.5
      days and was the same for the 204 clinically evaluable patients. Overall, the
      clinical cure rate for cefepime was 94% (191/204). Pathogen eradication was
      achieved in 93% (185/199) of infections. Of the patients with associated
      bacteraemia, the clinical cure rate was 97% (31/32) and 94% (16/17) of the
      pathogens were eradicated. Cefepime therapy was well-tolerated. Treatment was
      discontinued in eight patients (3%) because of local intolerance and in five
      patients (2%) because of drug-related adverse events (rash, headache and
      pruritus). Cefepime 1 g bd is as safe and effective as other parenteral
      cephalosporins for the treatment of acute bacterial UTI, LRTI and S/STI,
      including those cases with associated bacteraemia. The bd dosing schedule and
      reported lack of cross-resistance with other cephalosporins against some species
      of aerobic Gram-negative bacilli make cefepime an attractive treatment option in
      hospitalized patients.

PMID- 8150756
TI  - A comparative study of the in-vitro activity of cefepime and other antimicrobial
      agents against penicillin-susceptible and penicillin-resistant Streptococcus
      pneumoniae.
AB  - Using the national surveillance programme of USA hospitals, we selected 162
      strains of Streptococcus pneumoniae for sensitivity testing using the NCCLS
      breakpoints for benzylpenicillin and the oxacillin discs screen test. Included in
      the group of isolates were 85 relatively penicillin-resistant and 33 penicillin
      resistant strains. The activity of cefepime, a new cephalosporin, was compared
      with other cephalosporins and penicillins as well as some non-beta-lactam
      antimicrobials. Imipenem was the most active agent but, cefepime, cefotaxime,
      ceftriaxone and ciprofloxacin were only slightly less active. The least active
      agents were ceftazidime, cefuroxime, piperacillin/tazobactam and
      ticarcillin/clavulanate. Cefepime is a potential alternative treatment to
      penicillin, particularly when penicillin-resistant and relatively penicillin
      resistant S. pneumoniae are encountered. The clinical importance of screening for
      penicillin resistance by the use of the oxacillin disc is emphasized.

PMID- 8150757
TI  - A non-comparative, multicentre study of cefepime in the treatment of serious
      bacterial infections.
AB  - Multi-resistant strains of Gram-negative bacteria are rapidly emerging as a
      frequent cause of serious bacterial infection in the hospital environment.
      Effective treatment must include an antibiotic with activity against these
      organisms. In an open multicentre study, cefepime was evaluated as empirical
      therapy in 156 hospitalized patients (mean age 57 years) with serious infection
      of the urinary tract (n = 43), lower respiratory tract (n = 101) and skin and
      soft tissue (n = 12). In 18 patients, septicaemia/bacteraemia was also diagnosed.
      Cefepime, 2 g bd, was administered for a maximum of 16 days (mean 8). Of 98
      pathogens isolated, 75 were Gram-negative and 23 were Gram-positive species.
      Ninety-four of the pathogens were susceptible to cefepime, including multi
      resistant isolates such as Pseudomonas aeruginosa and Enterobacter cloacae. The
      overall clinical cure rate, excluding septicaemia/bacteraemia, was 92% (94/102);
      the corresponding bacterial eradication rate was 95% (52/55). In patients with
      septicaemia/bacteraemia, the clinical cure rate was 87% (13/15) despite
      eradication of 100% (11/11) of the assessable pathogens. Cefepime was well
      tolerated, although 14 (9%) patients experienced local intolerance at the
      infusion site. Other drug-related adverse events were reported in six (4%)
      patients and included diarrhoea, pruritus, rash and urticaria. Cefepime is safe
      and effective as empirical treatment for serious infections commonly found in the
      hospital setting. Clinical cure and bacterial eradication can be achieved with a
      convenient bd dosing schedule.

PMID- 8150758
TI  - Cefepime as treatment for osteomyelitis and other severe bacterial infections.
AB  - Cefepime, a novel, injectable alpha-methoxyimino aminothiazolyl cephalosporin, is
      active in vitro against many of the Gram-positive and Gram-negative bacteria
      which cause severe infections, including Pseudomonas aeruginosa. It is more
      active than existing third-generation cephalosporins against multiply-resistant
      strains of Enterobacteriaceae because of its low affinity for beta-lactamases and
      its resistance to hydrolysis by these enzymes. Cefepime retains its high potency
      of activity against methicillin-susceptible Staphylococcus aureus, coagulase
      negative staphylococci and streptococci other than enterococci. Seventy-four
      patients (46 male and 28 female) were treated with cefepime 2 g i.v. every 12 h;
      61 patients were evaluable for efficacy (39 male and 22 female). The infections
      included pneumonia caused by Gram-negative bacilli (21 patients, six with
      bacteraemia), septicaemia (seven), pyelonephritis (two), osteomyelitis (23,
      mainly caused by S. aureus), septic arthritis (four) and soft tissue infections
      (four, one with bacteraemia). Responses were as follows: 52 (85.3%) patients
      cured; three (4.9%) improved and six (9.8%) failed. The failures included three
      patients with osteomyelitis, one with pyelonephritis and two with pneumonia. The
      pathogens and eradication rates were: S. aureus 23/24 (96%), Staphylococcus
      epidermidis 4/4, Streptococcus spp. 10/10 (100%), P. aeruginosa 11/14 (79%),
      Enterobacteriaceae 28/28 (100%), Haemophilus spp. 3/3 and others 7/7. Clinical
      adverse effects included diarrhoea in 11 patients (14.9%) nausea in five (6.8%)
      and pruritus in three (4.1%). Laboratory abnormalities included leucopenia in
      three patients (4.1%) and direct Coombs' conversion in 32 (43.2%). Patients were
      treated for an average of 31.8 days for osteomyelitis and 11.9 days for other
      infections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150759
TI  - Cefepime monotherapy for the empirical treatment of fever in granulocytopenic
      cancer patients.
AB  - In a pilot study, we evaluated the efficacy and the safety of cefepime, a new
      cephalosporin with extended-spectrum activity against both Gram-positive and Gram
      negative bacteria, as empirical monotherapy for 108 febrile episodes in 84
      granulocytopenic cancer patients. Cefepime (2 g tds) was given for a minimum of 7
      days or until resolution of infection. Of the 108 episodes, 91 were evaluable.
      Microbiologically documented infections occurred in 25 patients (27%) (18 Gram
      positive, 7 Gram-negative), of whom 18 had bacteraemia. Infection was clinically
      documented in 47 patients (52%) and fever was unexplained in 19 (21%). Overall,
      71% (65/91) of the infections resolved. Response rates were 86% (6/7) for Gram
      negative infections, 44% (8/18) for Gram-positive infections (57% for cefepime
      susceptible Gram-positive bacteria), 77% (36/47) for clinically documented
      infections and 79% (15/19) for unexplained fevers. Of the 26 patients (29%) whose
      primary infections did not improve with cefepime monotherapy, 23 responded after
      the addition of other antibiotics. Sixteen patients (18%) developed secondary
      infections of which 13 were microbiologically documented; Gram-positive bacteria
      were isolated from seven patients, Gram-negative bacteria from two, fungi from
      three and a virus from one. Adverse effects were mild and did not require
      premature discontinuation of therapy except for one patient who developed an
      immediate allergic reaction after the first dose of cefepime from which he
      recovered fully. The survival rate after resolution of granulocytopenia was 96%;
      three patients died of primary bacterial infection and one from secondary
      disseminated candidiasis. In this pilot study, cefepime monotherapy appeared safe
      and effective as empirical therapy for fever in cancer patients with
      granulocytopenia. Whether cefepime is superior to other advanced-generation
      cephalosporins for the treatment of Gram-positive infections will require
      evaluation in a larger comparative study.

PMID- 8150760
TI  - A comparative study of cefepime and ceftazidime in the treatment of community
      acquired lower respiratory tract infections.
AB  - Antibiotic treatment for community-acquired pneumonia must target Gram-positive
      pathogens, especially frequently isolated organisms such as Streptococcus
      pneumoniae. The severity of community-acquired pneumonia is often related to
      underlying factors. Occasionally it may be complicated by staphylococcal or Gram
      negative bacillary infection. We have compared the safety and efficacy of
      cefepime 1 g bd with ceftazidime 1 g tds as empirical treatment in adults with
      community-acquired lower respiratory tract infections (LRTIs). One hundred and
      thirty-one patients with moderate to severe LRTIs were randomized to two
      treatment groups: 87 received cefepime and 44 received ceftazidime. The treatment
      groups were comparable with regard to sex, age and treatment duration. Of the 116
      pathogens isolated, 57 were Gram-positive (46 strains of S. pneumoniae) and 59
      were Gram-negative (33 strains of Haemophilus influenzae). Of the 111 patients
      evaluated, clinical cure rates were 87% (65/75) in the cefepime group and 86%
      (31/36) in the ceftazidime group. Pathogen eradication rates were 95% (74/78 and
      36/37, respectively) in both groups. Both drugs were well tolerated and the
      incidence of adverse events in each group was comparable. Cefepime 2 g per day (1
      g bd) was as safe and effective as ceftazidime 3 g per day (1 g tds) in the
      treatment of community-acquired LRTIs.

PMID- 8150761
TI  - International comparative study of cefepime and ceftazidime in the treatment of
      serious bacterial infections.
AB  - In this randomized multicentre study, we compared the safety and efficacy of
      cefepime, 2.0 g bd i.v., with that of ceftazidime, 2.0 g tid i.v., as initial
      treatment of adult patients with serious infections of bacterial aetiology. Three
      hundred and forty-eight patients were entered into the study, 173 received
      cefepime and 175 ceftazidime. The treatment groups were comparable with respect
      to demographic characteristics, including the types of infection
      (cefepime/ceftazidime: urinary tract, 55/72; lower respiratory tract, 83/74; skin
      and soft tissue, 23/14; septicaemia, 81/81; and others, 15/5). Gram-positive
      bacteria were identified as pathogens on 86 occasions (cefepime/ceftazidime:
      48/41), including 20 Staphylococcus aureus isolates (13/7) and 27 Streptococcus
      pneumoniae isolates (14/13). Gram-negative bacilli were isolated on 261 occasions
      (126/135), and included 219 Enterobacteriaceae (cefepime/ceftazidime: 108/111)
      and 34 strains of Pseudomonas aeruginosa (14/20). An intention-to-treat analysis
      revealed satisfactory clinical response rates of 80% and 79% for the cefepime and
      ceftazidime groups, respectively, and bacteriological eradication rates of 85%
      and 88% for the cefepime and ceftazidime groups, respectively. Of patients with
      microbiologically documented infections, 86% (84 of 98) treated with cefepime and
      87% (94 of 108) treated with ceftazidime responded satisfactorily. Thirty-two
      patients (19%) treated with cefepime and 26 (15%) treated with ceftazidime died.
      Thirty-six patients in the cefepime group and 23 in the ceftazidime group
      experienced adverse events; therapy was discontinued prematurely in four and two
      patients in the cefepime and ceftazidime groups, respectively. Of the patients
      experiencing adverse events, 22 (13%) treated with cefepime developed intolerance
      at the injection site, compared with 11 (6%) treated with ceftazidime (P =
      0.045). In conclusion, twice-daily cefepime (2 g bd) is at least as effective as
      ceftazidime (2 g tid), as initial empirical therapy for serious bacterial
      infections in non-neutropenic patients.

PMID- 8150762
TI  - Cefepime versus cefotaxime in the treatment of lower respiratory tract
      infections.
AB  - Patients with lower respiratory tract infection (LRTI) were randomized 2:1 to
      receive either cefepime 2 g i.v. bd or cefotaxime 2 g i.v. tds. Bronchopneumonia
      alone or associated with another LRTI was diagnosed in 30 of 37 cefepime
      recipients and in 11 of 18 cefotaxime recipients; other diagnoses included
      bronchitis, lobar pneumonia and aspiration pneumonia. The mean duration of
      treatment was 5.9 days in the cefepime group and 5.4 days in the cefotaxime
      group. There were no significant differences between the two groups with regard
      to clinical or bacteriological outcome. Treatment was associated with a
      satisfactory clinical response in 27 (73%) of 37 evaluable cefepime patients and
      in 10 (56%) of 18 evaluable cefotaxime patients. Treatment resulted in
      eradication of 33 (89%) of 37 pathogens in the cefepime group, including 13 of 15
      strains of Staphylococcus aureus, and of 16 (73%) of 22 pathogens in the
      cefotaxime group, including eight of ten strains of S. aureus. Two Pseudomonas
      aeruginosa strains persisted in the cefotaxime group. The sole clinical adverse
      event reported was a rash in one cefepime patient which did not require
      discontinuation of treatment. No clinically relevant changes in laboratory test
      results were attributed to either agent. Cefepime twice daily and cefotaxime
      three times daily were of comparable safety and efficacy in the treatment of
      bronchopneumonia and other LRTIs.

PMID- 8150763
TI  - Randomized comparative study of cefepime and cefotaxime in the treatment of acute
      obstetric and gynaecological infections.
AB  - Patients with presumed acute gynaecological infections were randomized (2:1) to
      receive cefepime 2 g every 12 h (n = 159) or cefotaxime 2 g every 8 h (n = 72),
      both im or by a 30-min i.v. infusion. For evaluation of efficacy, patients were
      required to have a bacteriologically documented infection, with at least one
      pathogen isolated susceptible to both drugs. Duration of treatment was 2-8 days
      in the 95 cefepime-treated patients and 3-10 days in the 36 cefotaxime-treated
      patients with evaluable infections; approximately three-quarters of the patients
      in each group were treated for 4-5 days. Clinical response was satisfactory in
      81/95 (85%) of the evaluable cefepime recipients and 30/36 (83%) of the evaluable
      cefotaxime recipients (P = 0.802). In total, 211 (85%) of the 247 pathogens
      isolated from evaluable cefepime recipients were eradicated, compared with 98
      (90%) of 109 pathogens isolated from evaluable cefotaxime recipients. All
      pathogens were eradicated in 77 (81%) cefepime-treated patients and in 31 (86%)
      cefotaxime-treated patients (P = 0.379). Overall response to treatment,
      calculated by combining clinical response and individual patient bacteriological
      response, was considered effective, partially effective or ineffective in 77%,
      13% and 11% of cefepime-treated patients respectively and in 75%, 19% and 6% of
      cefotaxime-treated patients respectively (P = 0.932 for effective response).
      Adverse clinical events were reported by 68 (43%) of 159 cefepime recipients and
      by 26 (36%) of 72 cefotaxime recipients (P = 0.342); adverse events were deemed
      drug-related in 6% of cefepime recipients (diarrhoea, rash and headache) and in
      1% of cefotaxime recipients (diarrhoea, pruritus and rash). Treatment was
      discontinued prematurely due to adverse events in five cefepime-treated patients
      and in one cefotaxime-treated patient (P = 0.476). Local intolerance was reported
      by 33 (21%) of the 159 cefepime-treated patients and by 14 (19%) of the 72
      cefotaxime-treated patients receiving drug via the iv route alone; none of the
      patients discontinued treatment because of local intolerance. Laboratory test
      abnormalities were observed in a small number of patients in each group (1-8%),
      but none warranted discontinuation of treatment. Cefepime 2 g bd appears to have
      efficacy and safety comparable to that of cefotaxime 2 g tid in the treatment of
      acute obstetric and gynaecological infections.

PMID- 8150764
TI  - A non-comparative study of the efficacy and tolerance of cefepime in combination
      with amikacin in the treatment of severe infections in patients in intensive
      care.
AB  - Patients in intensive care units (ICUs) are at increased risk of developing
      nosocomial infections. This is of special concern in the immunocompromised
      patient, particularly with regard to multiresistant pathogens. We evaluated the
      effectiveness of cefepime 2 g bd in combination with amikacin 7.5 mg/kg bd for
      the treatment of severe bacterial infection in 118 ICU patients, including 113
      patients with nosocomial lower respiratory tract infections (LRTI) (mean age, 51
      years). Ninety-six per cent (108/113) of the LRTI patients required respiratory
      assistance and 12% (14/113) had associated septicaemia/bacteraemia. Eighty-four
      per cent (95/113) had clinical signs of sepsis and 35% (39/113) had features of
      septic shock. The mean Simplified Acute Physiologic Score (SAPS) was 12 at
      inclusion. Seventy-nine patients with LRTI were clinically and bacteriologically
      evaluable. The causative pathogens were representative of those usually isolated
      in ICUs: Staphylococcus aureus (19%); Pseudomonas aeruginosa (14%); and
      Klebsiella, Enterobacter and Serratia spp. (17%). The clinical cure rate was 86%
      (68/79) while the pathogen eradication rate was 91% (107/117). Of the patients
      with associated septicaemia/bacteraemia, 89% (8/9) of the pathogens were
      eliminated. Cefepime-amikacin combination therapy was well tolerated; two
      patients discontinued treatment due to rashes. Combination therapy with cefepime
      2 g bd and amikacin 7.5 mg/kg bd appears safe and effective for the treatment of
      nosocomial pneumonia in patients hospitalized in ICUs. Further comparative
      controlled studies are justified.

PMID- 8150765
TI  - In-vitro activities of cefepime against Enterobacter cloacae, Serratia
      marcescens, Pseudomonas aeruginosa and other aerobic gram-negative bacilli.
AB  - Infections caused by resistant bacterial pathogens such as Citrobacter freundii,
      Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa have become
      an increasing problem with respect to therapy in large medical centres in Korea.
      The MICs of cefepime for aerobic Gram-negative bacilli isolated during 1991,
      mostly from in-patients in a hospital in Seoul, were determined by the agar
      dilution method and compared with those of several other antimicrobials. Of the
      agents tested, cefepime had the lowest MIC90s for C. freundii and E. cloacae
      (0.12 and 8 mg/L, respectively). The MIC90s of cefepime and amikacin (both 8
      mg/L) were the lowest for S. marcescens. The MIC90s of cefepime, ceftazidime and
      doxycycline (all 32 mg/L) were the lowest for Acinetobacter anitratus. For P.
      aeruginosa, the MIC90 was relatively high (32 mg/L) but still the lowest of the
      antimicrobials tested. Of the cefotaxime-resistant E. cloacae isolates studied,
      only 7% were resistant to cefepime, while 100%, 96% and 89% were resistant to
      ceftazidime, ceftizoxime and cefuzonam, respectively. Similarly, only 6% of
      gentamicin-resistant isolates were resistant to cefepime, compared with 91%, 72%,
      69% and 63% to ceftazidime, ceftizoxime, cefuzonam and cefotaxime, respectively.
      In conclusion, isolates from Korean patients are often resistant to several
      antimicrobial agents. However, based on the results of this study, cefepime may
      be very useful as treatment for patients with nosocomial infections caused by
      aerobic Gram-negative bacilli, including those which are resistant to most of the
      third-generation cephalosporins and gentamicin.

PMID- 8150766
TI  - In-vitro activity of cefepime and other antimicrobials: survey of European
      isolates.
AB  - Cefepime, a new cephalosporin which has a broad-spectrum of activity was tested
      in vitro against 1961 Gram-positive and Gram-negative clinical isolates obtained
      from European hospitals. Cefepime was highly active against Gram-negative
      organisms, inhibiting over 94% of strains tested. The overall susceptibility rate
      for cefepime against all isolates was 81%. Cefepime was more active than any of
      the third-generation cephalosporins tested against species capable of producing
      type I beta-lactamases, e.g. Enterobacter cloacae, Citrobacter freundii, and
      Enterobacter aerogenes. The activity of cefepime against Pseudomonas aeruginosa
      was similar to that of ceftazidime and substantially greater than those of
      cefotaxime and ceftriaxone. All cephalosporins except ceftazidime exhibited high
      activity against methicillin-susceptible Staphylococcus aureus but poor activity
      was observed against methicillin-resistant strains. Overall susceptibility to
      cefepime is lower in Europe than it is in North America.

PMID- 8150768
TI  - Activity of cefepime and other beta-lactam antibiotics against permeability
      mutants of Escherichia coli and Klebsiella pneumoniae.
AB  - Permeability mutants were obtained, under selection pressure with cefoxitin, from
      five strains each of Escherichia coli and Klebsiella pneumoniae. Most mutants
      showed alterations to their outer membrane protein profiles. In general, the
      porins OmpC and F were lost from E. coli mutants, and one or both components of a
      40 kD doublet were lost from K. pneumoniae mutants. Additional minor changes to
      outer membrane proteins, of unknown significance, were detected in many of the
      mutants. MICs of cefepime, ceftazidime and cefpirome for the porin-deficient
      mutants were up to 128-fold above those for their parent strains, but remained <
      or = 4 mg/L, whereas those of cefoxitin, cefuroxime, and penicillins were raised
      above accepted breakpoints. The detection of reduced susceptibility to third- and
      fourth-generation cephalosporins is in contrast to the findings of other groups.
      Most (9/10) mutants with high-level cefoxitin resistance were reasonably stable
      during sequential batch culture in rich media, but susceptible variants tended to
      overgrow under nutrient depletion in continuous culture. These variants were not
      true revertants, having failed to regain the major porins: rather they appeared
      to have undergone compensatory mutations. Their instability probably explains why
      porin-deficient enterobacteria have not become a significant clinical problem,
      despite the ease with which they can be selected in vitro.

PMID- 8150767
TI  - In-vitro antibacterial activity of cefepime: a multicentre study.
AB  - The antimicrobial activity of cefepime, a new broad-spectrum parenteral
      cephalosporin, was evaluated in vitro against 1757 recent clinical Gram-positive
      and Gram-negative isolates. Cefepime was active at low concentrations (MIC50
      values < or = 0.06 mg/L and MIC90 values < or = 0.12 mg/L) against non
      cephalosporinase-producing Enterobacteriaceae (Escherichia coli, Proteus
      mirabilis, Salmonella spp. and Shigella spp.). For Klebsiella pneumoniae, MICs
      were between 0.016 and 16 mg/L; the highest MIC values were observed for extended
      spectrum beta-lactamase-producing strains. Against Enterobacteriaceae, such as
      cephalosporinase producing Enterobacter cloacae, MICs were < or = 0.5 mg/L, but
      MICs against cephalosporinase hyperproducing strains were generally higher.
      Ticarcillin-sensitive strains of Pseudomonas aeruginosa were inhibited by
      cefepime concentrations of 0.5-16 mg/L, while cefepime MICs were 8-64 mg/L for
      strains resistant to ticarcillin. The cefepime MIC50 value for Haemophilus spp.
      including many resistant to amoxycillin, was 0.03 mg/L. Against methicillin
      sensitive strains of Staphylococcus aureus, cefepime MICs were 0.5-16 mg/L; MICs
      against methicillin-resistant staphylococci were 16- > 128 mg/L). Against
      methicillin-sensitive coagulase-negative staphylococci, cefepime MIC values were
      0.03-16 mg/L; corresponding values for methicillin-resistant strains were 2-128
      mg/L. Streptococci (Groups A, C and G) were sensitive to cefepime with MICs
      ranging from < or = 0.008-2 mg/L (MIC50, 0.03 mg/L; MIC90, 0.25 mg/L). The
      activity of cefepime against Group B streptococci and pneumococci were
      comparable, with MIC50 values of 0.12 and 0.25 mg/L, respectively, and MIC90
      values of 0.03 and 0.25 mg/L, respectively. Most enterococci and all Listeria
      monocytogenes strains had MICs > or = 32 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150769
TI  - Development of resistance in Pseudomonas aeruginosa to broad-spectrum
      cephalosporins via step-wise mutations.
AB  - Step-wise resistance to cefepime, ceftazidime, cefotaxime, and cefpirome were
      determined for 16 Pseudomonas aeruginosa strains by daily transfer for 7 days to
      fresh media containing two-fold serial dilution of antibiotic. By the third
      transfer 4 of 16 strains (25%) were resistant (MIC > or = 32 mg/L) to ceftazidime
      compared with none, five (31%) and ten (60%) strains becoming resistant to
      cefepime, cefpirome and cefotaxime (MIC > or = 64 mg/L), respectively. At the end
      of the 7 day serial transfer, only four (25%) of the 16 strains were resistant to
      cefepime, in contrast to nine (56%) cefpirome resistant, 12 (75%) ceftazidime
      resistant and 13 (81%) cefotaxime resistant. These results are consistent with
      the infrequent, single-step development of resistance to cefepime, and this may
      also explain the frequent cefepime susceptibility of cefotaxime/ceftazidime
      resistant clinical isolates of P. aeruginosa.

PMID- 8150770
TI  - Canadian survey of antimicrobial resistance in Klebsiella spp. and Enterobacter
      spp. The Canadian Antimicrobial Resistance Study Group.
AB  - Increasing antimicrobial resistance has been reported for Klebsiella spp. and
      Enterobacter spp. The in-vitro activities of 14 antimicrobial agents against 656
      clinical isolates of Klebsiella spp. and 630 isolates of Enterobacter spp.
      collected from seven cities in Canada were determined by microbroth dilution.
      There was no regional variation in the susceptibility patterns. Klebsiella spp.
      remain highly susceptible to most antimicrobials, only one isolate was resistant
      to third-generation cephalosporins. However, many isolates of Enterobacter spp.
      (> 16%) were resistant to the third-generation cephalosporins with marked cross
      resistance to piperacillin (63.1%), piperacillin/tazobactam (44.9%), and
      aztreonam (76.6%). Gentamicin, tobramycin, imipenem, ciprofloxacin, cefepime, and
      cefpirome were consistently active against most isolates of Enterobacter spp.
      including those resistant to the third-generation cephalosporins.

PMID- 8150771
TI  - Cefepime: overview of activity in vitro and in vivo.
AB  - Cefepime is a novel methoxyimino-aminothiazolyl cephalosporin with a quaternized
      N-methyl-pyrrolidine moiety at the 3' position conferring zwitterionic
      properties. Because of this the molecule penetrates the outer cell membrane of
      Gram-negative bacteria rapidly. In addition it is resistant to degradation by
      several plasmid and chromosomally-mediated beta-lactamases, for which it also
      shows very low affinity and no inducing capacity. It has good affinity for PBPs 2
      and 3 of Escherichia coli and for PBP 3 of Pseudomonas aeruginosa. Its broad
      spectrum of activity includes Gram-positive and Gram-negative pathogens. It is
      more active than cefotaxime or ceftazidime, against Enterobacteriaceae. The MIC90
      for P. aeruginosa is higher than that of ceftazidime, but lower than those of
      cefpirome, cefoperazone and latamoxef. Other Gram-negative organisms, Haemophilus
      influenzae, Neiserria meningitidis, Neiserria gonorrhoeae, Moraxella catarrhalis
      are highly susceptible to cefepime. Among Gram-positive species methicillin
      susceptible Staphylococcus aureus and coagulase-negative staphylococci, whether
      beta-lactamase producers or not, Streptococcus pneumoniae and Streptococcus
      pyogenes are susceptible. Cefepime is active against cefotaxime- and/or
      ceftazidime-resistant Enterobacteriaceae. Only strains of P. aeruginosa producing
      large amounts of beta-lactamase may be resistant to both ceftazidime and
      cefepime. In experimental infections such as meningitis, induced with various
      bacterial species in neonatal rats and chronic staphylococcal osteomyelitis in
      rabbits, cefepime has shown good efficacy.

PMID- 8150772
TI  - Efficacy of cefepime in a Staphylococcus aureus endocarditis rat model.
AB  - The efficacy of cefepime, a new broad-spectrum cephalosporin, was compared with
      those of cefpirome, ceftazidime, vancomycin, imipenem-cilastatin and penicillin G
      in a rat model of endocarditis caused by a methicillin-susceptible strain of
      Staphylococcus aureus. Rats were infected intravenously with approximately 10(5)
      cfu of a penicillin-resistant strain of S. aureus 24 h after placement of a
      catheter into the left ventricle of the heart via the carotid artery. Efficacy
      was evaluated by comparing bacterial counts in the cardiac vegetations of treated
      rats with those of untreated controls. Rats treated with cefepime, cefpirome,
      ceftazidime, imipenem-cilastatin and vancomycin showed a reduction in the number
      of bacteria recovered from cardiac vegetations compared with infected control
      animals; penicillin G was ineffective in this respect. Serum concentrations of
      the study antimicrobials were determined at selected times following the
      administration of a single subcutaneous dose. The pharmacokinetic parameters of
      the cephalosporins were similar in these animals. This study shows that cefepime
      may be of value in the treatment of staphylococcal endocarditis.

PMID- 8150773
TI  - Estrogen receptor molecular biology.
AB  - A greater understanding of the molecular biology of estrogen receptor (ER) will
      allow the extension of its utility as a target in therapy to an increased number
      of patients. The treatment of ER-positive breast cancer with antiestrogens
      involves a very sophisticated decision. Patients are treated with tamoxifen based
      on the direct measurement of the level of ER expression in the tumor and an
      indirect assessment of its activity through the measurement of an important
      target gene, progesterone receptor (PR). An understanding of the mixed agonist
      antagonist nature of tamoxifen has led to the development of pure antagonists
      with clinical potential. Thus, the hormonal therapy of breast cancer can serve as
      the paradigm for the rational treatment of cancer based on the presence of the
      specific target of the therapy in the tumor and an understanding at the molecular
      level of the function of that target.

PMID- 8150774
TI  - New directions for breast cancer therapeutic research.
AB  - For the past two decades, attempts to improve chemotherapy for patients with
      breast cancer have emphasized the use of currently available agents. Research by
      drug discovery programs of the National Cancer Institute has identified a number
      of clinically promising novel agents. Conceivably, within the next several years
      there could be a doubling of the chemotherapy armamentarium for breast cancer-
      more than 30 active cytotoxic agents.

PMID- 8150775
TI  - Navelbine and the anthrapyrazoles.
AB  - This article reviews the preclinical and early clinical development of navelbine
      and the anthrapyrazoles. The differences in structure from the "parent" compounds
      that may confer clinical advantages are discussed. The preclinical data, clinical
      pharmacology, and Phase I trials are reviewed. Further development of these drugs
      in Phase II trials and comparative studies is also discussed.

PMID- 8150776
TI  - The genetics of breast cancer.
AB  - Some of the genetic abnormalities that give rise to human breast cancer have been
      identified. This article reviews the biology of the oncogenes c-myc and neu and
      the antioncogene p53. Data supporting the role of these genes in the pathogenesis
      of human breast cancer are reviewed. Potential diagnostic and therapeutic
      applications that have developed out of our understanding of the molecular
      genetics of breast cancer are also discussed.

PMID- 8150777
TI  - Bisphosphonates in breast cancer patients with skeletal metastases.
AB  - The utility of bisphosphonates is well established in the treatment of acute
      hypercalcemia of malignancy. Bisphosphonates may also decrease the complications
      and morbidity of skeletal metastases. This article emphasizes the use of
      bisphosphonates in breast cancer patients with skeletal metastases.

PMID- 8150778
TI  - Mammography in women under 50.
AB  - In this article, the evidence relating to the evaluation of effectiveness of
      early detection of breast cancer in women age 40 to 49 is reviewed, in light of
      the considerable controversy that has arisen over whether women in this age group
      should be given routine mammography screening. Of necessity, evidence is also
      provided on its effectiveness in older women, to facilitate comparison.

PMID- 8150779
TI  - Hormone replacement therapy in women with a history of breast carcinoma.
AB  - Hormone replacement therapy in women with a history of successfully treated
      breast cancer is felt to be contraindicated. Very little direct information is
      available regarding the effect of such therapy in this patient population. This
      article reviews the evidence both supporting and refuting a causative role for
      estrogen and progesterone in breast cancer. The majority of evidence supports
      such a role. The use of tamoxifen as an alternative treatment modality is
      examined.

PMID- 8150780
TI  - A practical view of prognostic factors for staging, adjuvant treatment planning,
      and as baseline studies for possible future therapy.
AB  - At this time the initial prognostic assessment of breast cancer patients is still
      most powerfully driven by basic histopathologic information, axillary nodal
      involvement, and tumor size. Estrogen and progesterone receptor status are
      important initial pieces of information for many patients, but this information
      is more important in deciding the most appropriate type of treatment, rather than
      the prognosis of the patient. Histologic and nuclear grading can provide
      important prognostic information, but broader application of this information
      awaits better methods to ensure accuracy and decrease intraobserver variability.
      Whether flow cytometry-derived information can be used to select patient subsets
      at very low risk of relapse awaits prospective validation in cooperative group
      trials. A number of new prognostic tests such as cathepsin D that have shown
      promise in some studies await definitive prospective validation. Further
      development of techniques to integrate prognostic factor information and the use
      of this information in individualized prognostic factor decisions is needed.

PMID- 8150781
TI  - Adjuvant therapy of breast cancer.
AB  - This article examines questions about adjuvant systemic therapy, especially in
      premenopausal and postmenopausal women. The impact of adjuvant therapy on quality
      of life is addressed, as is the role of doxorubicin in adjuvant chemotherapy. The
      value of high dose adjuvant chemotherapy and late effects of adjuvant therapy are
      also examined.

PMID- 8150782
TI  - The use of hematopoietic growth factors to support cytotoxic chemotherapy for
      patients with breast cancer.
AB  - The rationale for the uses of hematopoietic growth factors in the treatment of
      breast cancer is reviewed. The historical background of development of these
      novel therapeutic agents is also summarized as it pertains to patients undergoing
      myelosuppressive treatments. Important areas of controversy in the clinical uses
      of hematopoietic growth factors are identified, and future research directions in
      this field are discussed.

PMID- 8150783
TI  - Growth factors and their receptors.
AB  - Breast cancer represents a type of malignancy that is amenable to therapy
      targeting growth factors and receptors. There is considerable evidence that
      signaling mechanisms involving growth factors and their receptors are important
      in the normal development of breast epithelium. Dysregulation of these pathways
      may contribute to the proliferative, invasive, and metastatic phenotypes of
      breast cancer cells in humans. Approaches being tested in the preclinical setting
      include antibodies or peptides that disrupt receptor-ligand interactions as well
      as other compounds that can interfere with downstream signalling.

PMID- 8150784
TI  - Overview of the biologic markers of breast cancer.
AB  - Breast cancer is a complex but increasingly well-understood disease. Clearly,
      multiple alterations from normal mammary cells are required to achieve a
      transformed phenotype. Furthermore, there may be several possible alterations
      within broad categories that will produce the transformations leading to the
      malignant state. The specific set of alterations within a given cancer may thus
      provide necessary information about how it is unique and how it may best be
      treated. Several of the newer biologic markers of breast cancer may provide very
      specific treatment information. erbB-2 may predict for improved response to
      doxorubicin, rather than CMF. hsp 27 may predict for failure of doxorubicin. pS2
      or EGFR may provide supplemental information predicting response to hormonal
      therapy. Each of these variables has strong evidence to support its use in this
      manner, but that evidence has been obtained on limited numbers of patients
      treated in a limited number of ways. The most established markers, with multiple
      studies indicating their prognostic benefit, are erbB-2, cathepsin D, and
      proliferation markers. Of the several proliferation markers there may be no one
      choice that is best. However, very clearly, any marker must be carefully assessed
      for appropriate cut-off values, and cut-off values established by one cohort of
      patients should be verified against another cohort of patients. The oncoproteins
      associated with cell cycle regulation (cyclin D, p53, Rb, and c-myc) have shown
      strong promise of providing important prognostic information. The limited studies
      to date indicate that these markers are independent of one another. Cell cycle
      regulation may be an area in which any defect may serve to deregulate the cell,
      and therefore several defects in one cell would be unlikely. The specific nature
      of the defect in a given cancer may be very important. With the advent of
      immunohistochemical methods to measure most of the markers, more information may
      become available. Finally, the burgeoning area of tumor-stromal interactions is
      replete with potentially important markers of cancer prognosis. The growth
      factors, which are marginally a part of this area owing to the probable
      importance of paracrine effects on cancer cell growth, have progressively
      developed a body of literature supporting their prognostic potential. However,
      they have rarely been studied in conjunction with the other aspects of tumor
      stromal cooperation. The markers of metastatic potential, nm23 and angiogenesis,
      have been shown in small cohorts to have considerable prognostic import.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8150785
TI  - Dilemmas and challenges: a clinician's perspective.

PMID- 8150786
TI  - Psychiatric confidentiality in child custody disputes.
AB  - OBJECTIVE: The various legal and ethical issues that may arise in the context of
      divorce proceedings when custody of a child is disputed are noted. A latent issue
      in such cases pertains to the treatment records of the parents, as well as the
      child, if any of the parties have ever been in any type of psychiatric treatment
      or mental health therapy. The principal parties may seek access to each others'
      records, and courts and attorneys may do so as well. METHOD: The issues that
      arise are explored by way of hypothetical clinical cases, as well as a
      consideration of leading appellate cases from different legal jurisdictions.
      RESULTS: Access to psychiatric treatment records is often handled in diverse ways
      by clinicians in disputed custody proceedings. Their clinical experience offers
      little to guide them in this confusing area. To complicate matters, legal rulings
      may differ from one jurisdiction to another as well as within one jurisdiction.
      Positions taken vary along a continuum from the extremes of advocating that all
      past and current psychiatric treatment records be made available in such
      disputes, to no records being made available. CONCLUSIONS: In the state of
      current confusion and risk for psychiatrists, as well as past and present
      patients, a proposal is made that only when issues of "parental fitness" are
      raised should consideration be given to the release of psychiatric treatment
      records, in contrast to the traditional rule of "best interests of the child,"
      which would continue to operate in other areas of family disputes.

PMID- 8150787
TI  - Thyroid function and attention-deficit hyperactivity disorder.
AB  - OBJECTIVE: To examine thyroid indices in a community referred sample of boys with
      attention-deficit hyperactivity disorder (ADHD) for evidence of generalized
      resistance to thyroid hormone (GRTH). METHOD: TSH, T3, and T4 values were
      gathered prospectively in 53 physician, school, and/or parent referred ADHD
      subjects, and in 41 age and gender-matched normal controls. RESULTS: None were in
      the range suggestive of global or pituitary thyroid hormone resistance.
      CONCLUSIONS: GRTH is rare, and thyroid function should not be measured routinely
      in nonfamilial ADHD.

PMID- 8150788
TI  - Self-reported inattention, impulsivity, and hyperactivity at ages 15 and 18 years
      in the general population.
AB  - OBJECTIVE: Prevalence, impact, and continuity of self-reported attention deficit
      disorder (ADD) symptomology from ages 15 to 18 years were examined in a
      longitudinal study of a New Zealand birth cohort. METHOD: At age 15, prevalence
      of ADD symptomology was estimated, with no gender differences found in self
      reported symptomology. Four adolescents (0.5%) met full DSM-III criteria for ADD.
      Adolescents scoring higher than 1.5 SD above the sample mean on total ADD symptom
      score were identified as having high levels of ADD symptomology. RESULTS: Male
      and female adolescents reporting ADD symptomology with (6% of males; 4% of
      females) and without history of behavior disorder (6% of males; 7% of females)
      did not differ in inattention and impulsivity, received more diagnoses other than
      ADD, and experienced more adverse educational and social outcomes at 15 and 18
      years than did the nonADD group. CONCLUSIONS: Findings pertaining to the ADD with
      history group were consistent with previous research on the outcome of
      hyperactive children, whereas the ADD without history group may be reflecting the
      onset of other pathology in adolescence. Results suggest adolescent self-report
      of attentional difficulties may be a clinically significant marker of adjustment
      difficulties for both males and females, but additional information likely is
      needed for accurate diagnosis.

PMID- 8150789
TI  - Prediction of antisocial behavior in attention-deficit hyperactivity disorder
      boys from aggression/defiance scores.
AB  - OBJECTIVE: To predict teen-age arrests from measures of childhood defiance in
      attention-deficit hyperactivity disorder (ADHD) boys. METHOD: Defiance ratings
      that were independent of hyperactivity were obtained on two groups of ADHD boys.
      Official arrest data obtained on all subjects 9 years later were used as the
      outcome measure. RESULTS: ADHD boys with high defiance ratings had significantly
      higher felony offender rates than did boys with low ratings. However, the ADHD
      boys with low ratings had significantly higher felony offender rates than did
      normal control boys. CONCLUSIONS: Clinicians and parents should be alerted to the
      fact that minor antisocial features in ADHD boys, such as defiance, signal an
      increased risk for later serious antisocial behavior. However, they should not be
      misled by the absence of defiance in ADHD boys to think that these boys are not
      at risk for serious antisocial behavior (arrests for serious criminal behavior)
      later in life.

PMID- 8150790
TI  - Effects of desipramine on autonomic control of the heart.
AB  - OBJECTIVE: To assess the effects of desipramine (DMI) on autonomic control of the
      heart. METHODS: Blood pressure, RR interval (the time between successive heart
      beats), and RR interval variability, a noninvasive measure of autonomic control
      of the heart, were assessed in 13 subjects younger than 30 years old. RESULTS:
      DMI treatment was associated with an increase in blood pressure, a decrease in RR
      interval, and a decline in low and high frequency RR interval variability.
      CONCLUSIONS: These preliminary data suggest that, in young people, DMI treatment
      produces a substantial decrease in parasympathetic input to the heart and an
      increase in the ratio of sympathetic to parasympathetic input, changes that in
      certain circumstances have been associated with an increased risk of arrhythmia.
      In exploring the cardiac effects of the tricyclic antidepressants (TCAs) in young
      people, the impact of TCAs on autonomic input to the heart should be examined.

PMID- 8150791
TI  - Prevalence of affective disorder in the child and adolescent offspring of a
      single kindred: a pilot study.
AB  - OBJECTIVE: The study determined the prevalence of psychiatric disorders among the
      child and adolescent offspring of an extended family identified through a proband
      with bipolar affective disorder. METHODS: All of the not mentally retarded
      offspring (ages 6 to 17 years) of a single extended bipolar affective disorder
      pedigree were studied. Data regarding psychiatric diagnoses, intelligence, school
      achievement, temperament, and family functioning were collected using structured
      and standardized instruments. RESULTS: When the child and adolescent offspring
      were stratified by degree of genetic relationship to an adult with an affective
      disorder, there were no differences in demographic variables, IQ, school
      achievement, or most temperamental and family characteristics. In contrast, there
      were increases in the rates of affective disorders and disruptive behavior
      disorders in the offspring that correlated with the degree of genetic
      relationship to an affected adult. CONCLUSIONS: The risk of developing an early
      onset affective disorder is correlated with the degree of genetic relatedness to
      affected adults in this single, extended family. This pilot study demonstrates
      that the inclusion of extended relatives in high-risk studies can enhance the
      discrimination of genetic and environmental contributions to the development of
      affective disorders.

PMID- 8150792
TI  - Concordance between mothers' reports and children's self-reports of depressive
      symptoms: a longitudinal study.
AB  - OBJECTIVE: Developmental factors and maternal depression were examined for their
      impact on mother-child and clinician-child agreement concerning children's
      internal depressive symptoms. METHOD: Data were derived from a clinically
      referred, racially mixed sample of school-age boys and girls (n = 113), with a
      study entry diagnosis of depression. Measures of agreement were based on parallel
      items from the self-rated Children's Depression Inventory, mother-rated Child
      Behavior Checklist, and clinician-rated, semistructured psychiatric interview
      with both the child and mother. Repeated measures of agreement were modeled
      longitudinally over a maximum of 7 years as a function of age, social-cognitive
      development, and maternal depression. Additional covariates were maternal
      psychopathology (excluding depression), socioeconomic status, and child's gender
      and verbal ability. RESULTS: Mother-child and clinician-child agreement increased
      as a function of the child's age during the follow-up and was consistently
      attenuated by maternal depression. Depressed mothers overrated their children's
      symptomatology as compared with the children's self-reports. CONCLUSIONS:
      Clinicians should consider the young patient's age and level of maternal
      depression when weighing the relative merits of self-report and parental report
      of the child's depressive symptoms. Additional research is necessary to
      understand the mechanisms of change in parent-child agreement.

PMID- 8150793
TI  - Cognitive distortions and psychiatric diagnosis in dually diagnosed adolescents.
AB  - OBJECTIVE: The purpose of this study was to examine the characteristics and
      patterns of cognitive distortions among psychiatrically hospitalized adolescents.
      METHOD: Measures of cognitive distortions, depression, and hopelessness were
      administered to 135 adolescents on two psychiatric inpatient units. Subjects were
      grouped according to their Axis I diagnoses: depression only, conduct disorder
      only, depression and substance abuse, conduct disorder and substance abuse, all
      three diagnoses, and none of the three diagnoses. RESULTS: Multivariate analyses
      of covariance indicated that differently diagnosed adolescents exhibited varying
      levels of cognitive distorting as measured by the Children's Negative Cognitive
      Errors Questionnaire (CNCEQ). In particular, adolescents with multiple Axis I
      diagnoses tended to score highest. On all but one of four CNCEQ subscales, the
      depression only group evidenced as much cognitive distortion as did the group
      with multiple diagnoses. However, each diagnostic grouping demonstrated its own
      somewhat distinct distortions based on CNCEQ subscales. CONCLUSIONS: Findings are
      discussed in terms of the utility of differentiating cognitive styles for
      subsequent treatment. It is suggested that disparate cognitive interventions
      could be matched with adolescents displaying particular problems.

PMID- 8150794
TI  - Suicidal children grow up: suicidal episodes and effects of treatment during
      follow-up.
AB  - OBJECTIVES: This paper describes risk for first recurrent suicidal episodes in
      follow-up of suicidal child psychiatric inpatients. It identifies relations
      between suicide attempts in follow-up and psychosocial and psychopharmacological
      treatments. METHODS: First suicidal episodes involving either suicidal ideation
      or a suicide attempt in a 6 to 8 year follow-up period were rated for 69 child
      psychiatric inpatients and 64 children selected from the community. Psychiatric
      treatments were determined from reports from multiple sources. RESULTS: Forty
      five percent of 133 subjects reported a suicidal episode during follow-up.
      Children who reported suicidal ideation or a suicide attempt were greater than
      twice as likely to report a suicidal episode in follow-up than were children from
      the community. Children treated with antidepressants in follow-up were more
      likely to attempt suicide than were those not treated with antidepressants.
      CONCLUSIONS: Close follow-up of suicidal children is warranted to identity risk
      and to intervene to prevent suicidal episodes. Lack of efficacy of naturalistic
      treatments implies that controlled treatment studies are needed to determine
      effective intervention for suicidal children.

PMID- 8150795
TI  - Major depression or uncomplicated bereavement? A follow-up of youth exposed to
      suicide.
AB  - OBJECTIVE: To determine whether the depressive reactions experienced by youth
      exposed to suicide were uncomplicated bereavement or major depression by
      examining the longitudinal risk of recurrent major depression. METHOD: The 121
      friends and acquaintances of 26 adolescent suicide victims were followed up 1 to
      18 months after an initial interview that took place around 6 months after the
      death of the suicide victim. A demographically similar group of 138 unexposed
      controls was also followed up. RESULTS: The median duration of depression in the
      37 subjects who became depressed after exposure was 8 months. The exposed group,
      compared with controls, had a higher rate of incident depression (RR = 1.7, 95%
      Cl = 1.0-2.8) during the follow-up period, even after adjustment for previous
      history of depression and other risk factors for depression. Within the group of
      exposed subjects, the rate of depression on follow-up was highest in those who
      developed a depressive disorder before exposure to suicide, intermediate in those
      who developed depression after exposure, and lowest in those who were not
      depressed at the first interview after exposure. There was no evidence of an
      increased incidence of suicide attempts in the exposed group relative to the
      unexposed controls on follow-up. CONCLUSIONS: The depressive reactions observed
      in youth exposed to suicide are most consistent with major depressive episodes on
      the basis of course and risk of recurrence. Exposure to suicide was associated
      with an increased risk of recurrent depression but not with an increased long
      term risk of suicidal behavior.

PMID- 8150796
TI  - Suicidal ideation and suicide attempts among youth with insulin-dependent
      diabetes mellitus.
AB  - OBJECTIVE: To investigate the prevalence and correlates of suicidal behaviors
      among youth with insulin-dependent diabetes mellitus (IDDM) for up to 12 years
      after disease onset. METHOD: The occurrence of suicidal ideation and suicide
      attempts was assessed shortly after disease onset and repeatedly thereafter as
      part of a longitudinal study of diabetic children. Initial psychiatric status and
      symptomatology, characteristics of the medical illness, and sociodemographic
      variables were considered as potential correlates of suicidal behaviors. RESULTS:
      Young patients evidenced higher than expected rates of suicidal ideation, but
      relatively few attempted suicide over the follow-up. Among those who did attempt
      suicide, diabetes-related methods commonly were used. Suicidal ideation shortly
      after IDDM onset was related only to concurrent severity of depressive symptoms.
      Suicidal ideation over the follow-up was associated with later noncompliance with
      the medical regimen. CONCLUSIONS: Clinicians should be alert to the possibility
      of suicidal ideation among youth with IDDM because of the prevalence of those
      cognitions, the potential lethality of attempts due to insulin misuse, and the
      relationship of suicidal thoughts to later noncompliance with the medical
      regimen.

PMID- 8150797
TI  - Symptoms of schizotypal personality disorder in fragile X women.
AB  - OBJECTIVE: The frequency of DSM III-R symptoms of schizotypal personality
      disorder as it relates to CGG amplification and to the cytogenetic expression of
      fragile X syndrome was explored. METHOD: Four groups of women were examined: 30
      control mothers of children with developmental problems, 17 control women who
      grew up in fragile X families, 28 women cytogenetically negative but DNA positive
      for fragile X with a premutation, and 31 women who were DNA positive with an
      expanded mutation, most of whom were cytogenetically positive. All women were
      assessed using the Structured Interview for Schizotypy. RESULTS: Eight of the
      nine women who received the DSM III-R schizotypal personality disorder diagnosis
      came from the two fragile X groups: four from the premutation group and four from
      the expanded mutation group. Twenty percent of fragile X carriers who received
      the gene from their mother, but none who received the gene from their father
      demonstrated schizotypal personality disorder. CONCLUSIONS: Women who carry the
      premutation and women with the full mutation may both show schizotypal features,
      although less commonly than previously reported.

PMID- 8150799
TI  - Treatment with propranolol of severe self-injurious behavior in a blind, deaf,
      retarded adolescent.
AB  - Self-injurious behavior represents a significant barrier to behavioral
      interventions with retarded children. The etiology of this behavior is
      hypothesized as secondary to a state of overarousal. beta blockers are believed
      to be uniquely useful medications in having an effect on self-injurious behaviors
      through their ability to reduce arousal in the face of stimulation and demands.
      The case presented describes a multiply handicapped adolescent with severe self
      injury who responded to 300 mg of propranolol with a gradual but steady reduction
      in self-injury over 12 months. Concurrent with this was the emergence of
      increased interactions and benefit from behavioral interventions.

PMID- 8150798
TI  - Behavioral and psychiatric disorders in adult male carriers of fragile X.
AB  - OBJECTIVE: In the present study we examined the incidence of psychiatric and
      behavioral problems among male carriers of the fragile X gene. METHOD:
      Retrospective data on carrier males were gathered using the family informant
      method. Each of 56 fragile X carrier women was interviewed about her father by an
      examiner blind to the father's carrier status. The interviewer administered
      measures of (1) behaviors related to DSM-III-R Axis I disorders, (2) adult
      attention-deficit hyperactivity disorder (ADHD) behaviors, (3) parental bonding
      skills, and (4) abusive behaviors. The endorsements from 24 women with fragile X
      fathers were compared with endorsements from 32 women with nonfragile X fathers.
      RESULTS: The results show a higher incidence of psychopathology among the fragile
      X males (relative to nonfragile X fathers) for behaviors related to adult ADHD,
      parental bonding, abuse; and particularly for alcohol abuse/dependence and
      obsessive-compulsive disorder behaviors. CONCLUSIONS: These findings support the
      hypotheses that some "nonpenetrant" males may indeed be mildly affected carriers
      and that there is a broad spectrum of involvement among carrier males.

PMID- 8150800
TI  - Clinical effects of buspirone on intractable self-injury in adults with mental
      retardation.
AB  - OBJECTIVE: The efficacy of buspirone in controlling self-injurious behavior was
      examined in five individuals with mental retardation. Buspirone was used alone in
      two individuals and as an adjunct to thioridazine in the other three. METHOD:
      Standard behavioral observation methods were used to collect data on the number
      of self-injurious responses of the individuals during baseline and several doses
      of buspirone in an open trial. RESULTS: When compared with baseline levels, all
      five individuals showed some response to buspirone, with reductions in self
      injury ranging from 13% to 72%, depending on the dose. The most effective dose of
      buspirone was 30 mg/day for three individuals and 52.5 mg/day for the other two.
      These individuals were maintained for 6 to 33 weeks on their most effective dose.
      Coexistent symptoms of anxiety did not predict a favorable response to buspirone
      therapy. CONCLUSIONS: Buspirone showed a mixed but generally favorable response
      in controlling intractable self-injury in this and four previous studies
      reporting similar cases. However, the drug should not be endorsed as a proved
      treatment for self-injury until similar results have been obtained from well
      controlled studies of its efficacy.

PMID- 8150801
TI  - The outpatient milieu.

PMID- 8150802
TI  - Child-adult anxiety disorders.

PMID- 8150803
TI  - Clonidine for stimulant-related sleep problems.

PMID- 8150804
TI  - Medications for aggressiveness.

PMID- 8150805
TI  - The selective mutism controversy (continued)

PMID- 8150806
TI  - The inpatient crunch (continued)

PMID- 8150807
TI  - Purinoceptors modulating the release of noradrenaline.

PMID- 8150808
TI  - Adrenoceptors and their signal transduction mechanisms.

PMID- 8150809
TI  - Spectral analysis of blood pressure and heart rate variability in response to
      stress from air-jet in the Lyon rat.
AB  - 1. Power spectral analysis of the frequency of wave-forms of blood pressure and
      heart rate was used to characterize short-term fluctuations of these parameters
      in three strains of conscious Lyon rat, normotensive (LL and LN) and hypertensive
      LH. 2. A mild stress produced by means of a jet of air elicited blood pressure
      rises, associated with tachycardia. This response was of similar magnitude in the
      three strains. The stressor amplified the medium frequency (195-605 mHz) Mayer
      waves of blood pressure and heart rate which are under autonomic control. 3.
      Clonidine (10 micrograms kg-1 i.v.) lowered blood pressure and heart rate and
      dramatically reduced the amplitude of blood pressure and heart rate oscillations
      in the frequency region of 195-605 mHz. 4. A jet of air applied after clonidine
      administration led to blood pressure rise associated with tachycardia and
      enhanced oscillations in the 195-605 mHz region. 5. These results indicate that
      in Lyon normotensive and hypertensive rats, a mild emotional stressor elicits
      blood pressure and heart rate rises associated with spectral modifications
      reflecting sympathetic hyperactivity. Clonidine lowers blood pressure and heart
      rate and reduces their related variabilities. This effect is more pronounced in
      LH rats than in their normotensive controls. Clonidine appears to reduce the
      autonomic response to stress as indicated by the medium frequency oscillations.

PMID- 8150810
TI  - Pharmacological characterization and autoradiographic localization of dopamine
      receptors in the portal vein.
AB  - 1. Dopamine (DA) and DA receptor agonists exert a variety of effects on the
      cardiovascular system through interaction with specific DA receptors, including
      decreases in blood pressure and heart rate. 2. The decrease in blood pressure is
      due primarily to arterial vasodilation. This phenomenon is due to the stimulation
      of both postjunctional (D1-like or DA1) and prejunctional (D2-like or DA2)
      receptors causing respectively relaxation of arterial smooth muscle and decrease
      of the sympathetic vasoconstriction tone. 3. In view of the lack of detailed
      information on the existence of DA receptors in venous tissue, we have analysed
      D1-like and D2-like receptors in the rat portal vein using radioligand binding
      techniques associated with light microscope autoradiography. 4. No D1-like
      receptors were demonstrated in sections of the rat portal vein, whereas the D2
      like receptor ligand, [3H]-spiroperidol, was bound to sections of the vein in a
      manner consistent with the labelling of D2-like sites. Anatomically, D2-like
      sites were located within the tunica adventitia, including the adventitia-media
      border, and in the endothelium. 5. These findings suggest the existence of D2
      like but not D1-like receptor sites in the rat portal vein. D2-like sites of the
      tunica adventitia are probably prejunctional and involved in the modulation of
      sympathetic outflow. The functional significance of endothelial D2-like sites, if
      any, should be clarified in future studies.

PMID- 8150811
TI  - Opiate and opiate antidiarrhoeal drug action on rat isolated intestine.
AB  - 1. Stimulation of segments of rat jejunum (2.5, 5, 10, 20 and 40 Hz for 8 s) and
      ileum (10 Hz) resulted in a fast atropine-sensitive contraction during
      stimulation and a non-cholinergic after-contraction. Stimulation of segments with
      single pulses at 0.1 Hz had no effect. The colon (10 Hz) usually responded only
      with single large atropine-sensitive contractions. 2. The responses of the
      jejunum (2.5-40 Hz, 8 s) were unaffected by the mu-receptor ligands morphine (0.3
      microM) and RX 783006 (0.3 microM) or the kappa-receptor ligand,
      ethylketocyclazocine (0.3 microM). The cholinergic contraction of the colon was
      unaffected by ethylketocyclazocine (0.3 microM), but was reduced slightly by
      morphine at high concentrations only. 3. The prototype delta-opiate receptor
      ligand D-Ala2-D-Leu5-enkephalin (DADLE; 30 nM) reduced the contraction during
      stimulation (2.5, 5, 10 and 20 Hz for 8 s) of the rat jejunum. The IC50 value for
      inhibition of the contraction elicited by stimulation at 10 Hz was 3.2 in the
      jejunum and was 12 nM in the ileum. Contractions of the colon were only slightly
      inhibited at a high concentration of DADLE (1 microM). 4. DADLE had no effect on
      contractions elicited by acetylcholine, at a concentration of up to 3 microM in
      segments of jejunum. Naloxone (1 microM) abolished the inhibitory effect of DADLE
      on the cholinergic contraction of the electrically stimulated jejunum. In
      addition, naloxone caused a large enhancement of control responses to
      stimulation. 5. Only high concentrations of the antidiarrhoeals loperamide and
      diphenoxylate inhibited the contraction elicited at 10 Hz in the jejunum (IC50,
      1.3 and 7.1 microM, respectively) and ileum (loperamide IC50, 0.5 microM). The
      same concentrations of these drugs also inhibited the effect of exogenously added
      acetylcholine. A similar pattern of findings was made in the colon. 6. The
      results show marked differences in responses to transmural stimulation and to
      opiate drugs compared to those previously obtained from guinea-pig
      ileum.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8150812
TI  - In vivo kinetics of catecholamines.

PMID- 8150813
TI  - Extraneuronal transport of noradrenaline.

PMID- 8150814
TI  - Orthopaedic windows.

PMID- 8150815
TI  - Synoviorthesis with colloidal 32P chromic phosphate for the treatment of
      hemophilic arthropathy.
AB  - Between 1977 and 1992, we performed ninety-two synoviortheses (destruction of
      synovial tissue by intra-articular injection of a radioactive agent) on forty
      eight patients who had a severe congenital disorder of hemostasis and chronic
      hemophilic synovitis that was resistant to conventional treatment. Colloidal 32P
      chromic phosphate was injected intra-articularly: 1.0 millicurie for knees and
      0.5 millicurie for other joints. The duration of follow-up ranged from one to
      fifteen years. The frequency and importance of bleeding decreased in most of the
      patients. The range of motion of half of the joints remained stable or improved
      and that of the other half continued to decrease. Radiographic scores worsened
      progressively despite the decreased frequency of hemarthrosis. In most patients,
      the extra-articular leakage of the radioactive agent was slight. Chromosome
      breakages were observed almost exclusively in patients who were seropositive for
      human immunodeficiency virus and in whom the CD4-lymphocyte count was decreased
      from normal. The patients' level of satisfaction with the results was high.

PMID- 8150816
TI  - Low-power electromagnetic stimulation of osteotomized rabbit fibulae. A
      randomized, blinded study.
AB  - The purpose of this study was to determine whether low-power-consuming
      symmetrical-waveform electromagnetic stimuli could increase the stiffness of
      fracture sites in a rabbit fibular-osteotomy model. Both active and placebo
      devices were used in a blinded study protocol. Dose-response studies of pulse
      amplitude and pulse width were performed by continuous application (twenty-four
      hours a day) of repetitive (fifteen-hertz), bursted (five-millisecond-long)
      symmetrical, rectangular electromagnetic stimulus waveforms. The power consumed
      by these stimuli is approximately one-fifth that consumed by the pulsing
      electromagnetic field devices that are in current clinical use. Significant
      increase of callus bending stiffness was produced by pulse widths of five to
      seven microseconds and pulse amplitudes of fifty to 100 millivolts.

PMID- 8150817
TI  - Hematogenous osteomyelitis in infants and children in the northwestern region of
      Namibia. Management and two-year results.
AB  - We reviewed the records of fifty-five children, including eleven infants (three
      of whom were neonates), who had at least one skeletal manifestation of
      hematogenous osteomyelitis. Forty-two of the patients were boys and thirteen were
      girls. The patients were classified into three groups: those who had early acute,
      those who had late acute, and those who had chronic osteomyelitis. This
      classification system was based on clinical and radiographic criteria. Seven
      patients had early acute osteomyelitis; eighteen, late acute osteomyelitis; and
      thirty, chronic osteomyelitis. The bones most often affected were the tibia
      (twenty-two patients) and the femur (nineteen patients). Penicillin-resistant
      Staphylococcus aureus grew on culture of specimens of purulent material from
      twenty-nine (76 per cent) of thirty-eight patients. Escherichia coli, Proteus
      mirabilis, and Enterobacter grew on culture of specimens of purulent material
      from one patient each. Six cultures showed no growth. No purulent material was
      obtained from seventeen of the fifty-five patients. The seven patients who had
      early acute osteomyelitis, and four of the eighteen patients who had late acute
      osteomyelitis, responded well to antibiotic treatment only. A combination of
      antibiotic and operative treatment was needed in fourteen of the eighteen
      patients who had late acute osteomyelitis and in all thirty patients who had
      chronic osteomyelitis. Forty-nine of the fifty-five patients were followed for
      two years; the remaining six patients were lost to follow-up. The two-year
      results were good in nineteen of the twenty-three patients who had acute (early
      or late) osteomyelitis and in fifteen of the twenty-six patients who had chronic
      osteomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150818
TI  - An in vivo comparison between intraoperative isometric measurement and local
      elongation of the graft after reconstruction of the anterior cruciate ligament.
AB  - This study was designed to determine if isometric measurement can be used to
      predict the pattern of elongation (the change in length) of a bone-patellar
      ligament-bone graft during passive flexion-extension of the knee at the time of
      reconstruction of the anterior cruciate ligament in vivo. A standard operative
      reconstruction technique was performed on nine patients. The tunnel sites for the
      grafts were selected, and the change in the distance between these sites was
      measured, with use of a CA-5000 drill-guide isometer as the knee was subjected to
      passive flexion-extension. After the reconstruction was completed, a Hall-effect
      transducer was implanted in the graft to measure the local displacement in the
      mid-substance of the graft that was produced by passive flexion-extension of the
      knee. For comparison, the isometric measurements and the values for local
      displacement of the graft were normalized by calculation of the percentage change
      in the length. With the knee in 10 to 30 degrees of flexion, the average
      isometric measurements and the measurements of local displacement demonstrated a
      decrease in length; however, the two techniques of measurement deviated at angles
      of flexion of 40 degrees and more. On the average, the isometric measurement of
      elongation between the trial insertion sites predicted that the graft would
      increase in length in flexion relative to extension, in contrast to the response
      of the graft after fixation. There was no significant correlation between the
      isometric measurements and the local elongation of the graft (r2 =
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150819
TI  - The measurement of elongation of anterior cruciate-ligament grafts in vivo.
AB  - Many investigators who have studied the mechanical behavior of anterior cruciate
      ligament grafts have attributed the increase in anterior translation of the tibia
      relative to the femur (an increase in the anterior laxity of the knee joint) to
      the temporal changes in the material behavior (strength and elastic properties)
      of the graft that occur throughout the process of remodeling. However, with the
      onset of motion of the joint, it is unclear whether the repeatable mechanical
      behavior of the graft remains unchanged immediately after fixation, if the
      fixation slips, or if the length of the graft changes and produces an increase in
      anterior translation of the tibia relative to the femur. It is also unknown if
      procedures performed by different surgeons, using similar graft material and
      similar operative techniques, can produce similar mechanical behavior of the
      graft, or if the behavior of the graft is similar to that of the normal anterior
      cruciate ligament. In an effort to address these questions, two surgeons
      performed a reconstruction of the anterior cruciate ligament on ten patients each
      (groups 1 and 2) with use of a bone-patellar ligament-bone graft. Immediately
      after fixation of the graft, a Hall-effect transducer was implanted to measure
      the changes in the length of the mid-substance of the graft while the knee was
      moved through twenty cycles of passive flexion-extension. Unlike the length
      pattern of the normal anterior cruciate ligament, the length pattern of the graft
      changed during the initial cycles of passive motion of the knee. We defined this
      phenomenon as the cyclic response of the graft and characterized it by
      calculation of the changes in the length of the graft at fixed positions of the
      knee across the multiple cycles of passive motion. In some patients, the length
      of the graft increased through the initial passive-motion cycles, while in
      others, it decreased. With the knee nearly extended, the predicted increase in
      anterior translation of the tibia relative to the femur, resulting from the
      increase in the length of the graft, was a maximum of 1.0 millimeter. This
      indicates that increases in anterior translation of the tibia relative to the
      femur can occur immediately after reconstruction of the anterior cruciate
      ligament and that changes in the length of the graft occur after fixation at
      loads that are less than the ultimate failure load of the graft or of the
      fixation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8150820
TI  - Posteromedial pivot shift of the knee: a new test for rupture of the posterior
      cruciate ligament. A demonstration in six patients and a study of anatomical
      specimens.
AB  - A new test--the posteromedial pivot-shift test--was used to demonstrate a rupture
      of the posterior cruciate ligament of the knee in six patients. An anatomical
      study of seventeen specimens showed that in order for the posteromedial pivot
      shift to occur, the posterior collateral ligament, the medial collateral
      ligament, and the posterior oblique ligament must be cut; if one of these three
      ligaments is intact, the subluxation will not occur.

PMID- 8150821
TI  - The biological and biomechanical effects of irradiation on anterior spinal bone
      grafts in a canine model.
AB  - We evaluated the effects of irradiation on the healing of anterior vertebral
      strut grafts with use of a canine model. Through a left thoracotomy, a partial
      corpectomy of the seventh thoracic vertebra and autogenous iliac strut-grafting
      from the sixth to the eighth thoracic levels were performed in twenty-two adult
      beagles. Four groups were established: Group I (control) received no irradiation,
      Group II received preoperative irradiation, Group III received postoperative
      irradiation that began on the third postoperative day, and Group IV received
      postoperative irradiation that began on the twenty-first postoperative day. The
      irradiation protocol was five treatments of 500 centigray three times a week for
      a total of 2500 centigray. Fluorochromes were administered at regular intervals
      postoperatively. The beagles were killed three months postoperatively, and non
      destructive biomechanical testing was done to evaluate the stiffness of the
      construct. The quality of healing at the junctions of the graft with the sixth
      and eighth thoracic vertebrae, the degree of revascularization of the graft, and
      the amount of new-bone formation were evaluated histologically. Statistical
      evaluation of the biomechanical data revealed no significant difference in the
      stiffness of the construct between Groups I, II, and IV. The specimens from Group
      III were significantly less stiff than those from Group I (the control group) in
      torsion (p = 0.03) and left lateral bending (p = 0.04) and than those from Group
      II in flexion (p = 0.02) and left lateral bending (p = 0.005).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8150822
TI  - Osteoarticular allografts for reconstruction after resection of a musculoskeletal
      tumor in the proximal end of the tibia.
AB  - An osteoarticular allograft was used to reconstruct a skeletal deficiency in
      sixteen patients after resection of a tumor in the proximal end of the tibia. The
      status of each allograft and the condition of each involved limb were evaluated
      an average of nine years (range, six to fourteen years) postoperatively. The
      status of the allograft was evaluated according to the survival of the allograft
      and the occurrence of complications. Of the original sixteen allografts, seven
      were removed: six, between two and five years after the reconstruction and one,
      seven years after the reconstruction. A second reconstruction with use of an
      allograft was performed in five of the seven patients. Fifteen complications
      occurred in association with eleven of the original sixteen allografts. These
      included fracture of the allograft (five patients), subchondral collapse (five
      patients), infection (two patients), non-union (two patients), and instability of
      the joint (one patient). At the latest follow-up examination, nine patients had
      retained the original allograft, five had had a second allograft procedure, and
      two had had an above-the-knee amputation. The most recent result was rated
      excellent or good in eleven patients and fair or a failure in five, with use of
      the system of Mankin et al. It was rated good or excellent in nine patients and
      fair, poor, or a failure in six, and it was not rated in one patient who had
      died, according to the system of the Musculoskeletal Tumor Society.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8150823
TI  - Reflex inhibition of the quadriceps femoris muscle after injury or reconstruction
      of the anterior cruciate ligament.
AB  - A burst-superimposition technique was used to assess the strength of the
      quadriceps femoris muscle in three groups of patients. Group 1 comprised twenty
      patients who had had a torn anterior cruciate ligament of the knee and had a
      reconstruction of the ligament one to six months after the injury. Group 2
      comprised twelve patients who had had a torn anterior cruciate ligament for an
      average of three months (a subacute tear). Group 3 comprised eight patients who
      had had a torn anterior cruciate ligament for an average of two years (a chronic
      tear). The patients in Groups 2 and 3 had not had an operation for the torn
      ligament. The patients in Groups 1 and 3 had no evidence of failure of activation
      of the involved quadriceps, but nine of the twelve patients in Group 2 had reflex
      inhibition of contraction of the muscle.

PMID- 8150824
TI  - Undiagnosed fractures in severely injured children and young adults.
      Identification with technetium imaging.
AB  - A whole-body bone scan was performed to search for undetected fractures in forty
      eight patients who had multiple injuries or a head injury, or both, and who were
      less than twenty-two years old. The study took place from January 1991 to July
      1992. Radiographs had been made of all areas of suspected skeletal trauma at the
      time of admission. Follow-up plain radiographs were made of all areas where
      unexpected abnormal tracer activity was noted. Forty-two of these areas were
      noted in eighteen skeletally immature patients and fifty-two, in twelve
      skeletally mature patients. Nineteen previously unrecognized fractures were
      identified in the subsequent radiographic analysis. Four skeletally immature and
      two skeletally mature patients had an alteration in treatment on the basis of the
      identification of a previously undiagnosed injury. Each of these six patients had
      a cast applied. A fracture was identified three weeks or more after the injury in
      two skeletally mature patients. These fractures would have been treated (one with
      a cast and the other with open reduction and internal fixation) if they had been
      diagnosed earlier. We believe that this analysis demonstrates the usefulness of
      technetium radionucleotide bone-imaging, as an adjuvant to the orthopaedic
      examination, in the identification of undiagnosed musculoskeletal injuries in a
      patient who is less that twenty-two years old and who has sustained a head injury
      or multiple injuries, or both.

PMID- 8150825
TI  - Painful bipartite patella. A new approach to operative treatment.
AB  - Thirteen patients who had fifteen painful bipartite patellae were managed with a
      new operative technique in which the vastus lateralis insertion to the painful
      patellar fragment is detached subperiosteally while the continuity of the tendon
      periosteum complex to the main portion of the patella is preserved. A grossly
      mobile patellar fragment was removed from five patellae (three type-II and two
      type-III according to the classification of Saupe). A fragment that showed
      minimum mobility was left in situ in seven type-III and three type-II patellae.
      All of the patients had prompt relief of the pain and returned to full sports
      activity within two months after the operation. Six of the seven type-III
      fragments that had not been removed united by bone to the main portion of the
      patella within two years postoperatively, but all three type-II fragments failed
      to unite. Over-all, eleven patients (thirteen knees) had an excellent result at
      an average of five years postoperatively.

PMID- 8150826
TI  - Mesenchymal cell-based repair of large, full-thickness defects of articular
      cartilage.
AB  - Osteochondral progenitor cells were used to repair large, full-thickness defects
      of the articular cartilage that had been created in the knees of rabbits.
      Adherent cells from bone marrow, or cells from the periosteum that had been
      liberated from connective tissue by collagenase digestion, were grown in culture,
      dispersed in a type-I collagen gel, and transplanted into a large (three-by-six
      millimeter), full-thickness (three-millimeter) defect in the weight-bearing
      surface of the medial femoral condyle. The contralateral knee served as a
      control: either the defect in that knee was left empty or a cell-free collagen
      gel was implanted. The periosteal and the bone-marrow-derived cells showed
      similar patterns of differentiation into articular cartilage and subchondral
      bone. Specimens of reparative tissue were analyzed with use of a semiquantitative
      histological grading system and by mechanical testing with employment of a porous
      indenter to measure the compliance of the tissue at intervals until twenty-four
      weeks after the operation. There was no apparent difference between the results
      obtained with the cells from the bone marrow and those from the periosteum. As
      early as two weeks after transplantation, the autologous osteochondral progenitor
      cells had uniformly differentiated into chondrocytes throughout the defects. This
      repair cartilage was subsequently replaced with bone in a proximal-to-distal
      direction, until, at twenty-four weeks after transplantation, the subchondral
      bone was completely repaired, without loss of overlying articular cartilage. The
      mechanical testing data were a useful index of the quality of the long-term
      repair. Twenty-four weeks after transplantation, the reparative tissue of both
      the bone-marrow and the periosteal cells was stiffer and less compliant than the
      tissue derived from the empty defects but less stiff and more compliant than
      normal cartilage. CLINICAL RELEVANCE: The current modalities for the repair of
      defects of the articular cartilage have many disadvantages. The transplantation
      of progenitor cells that will form cartilage and bone offers a possible
      alternative to these methods. As demonstrated in this report, autologous, bone
      marrow-derived, osteochondral progenitor cells can be isolated and grown in vitro
      without the loss of their capacity to differentiate into cartilage or bone.
      Sufficient autologous cells can be generated to initiate the repair of articular
      cartilage and the reformation of subchondral bone. The repair tissues appear to
      undergo the same developmental transitions that originally led to the formation
      of articular tissue in the embryo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8150827
TI  - Pigmented villonodular synovitis presenting as a popliteal cyst in a child. A
      case report.

PMID- 8150828
TI  - Magnetic resonance-imaging scans in discitis. Sequential studies in a child who
      needed operative drainage: a case report.

PMID- 8150829
TI  - Preoperative location of a lesion with a guide-wire under ultrasonic control: an
      alternative to intraoperative fluoroscopy. A case report.

PMID- 8150830
TI  - Distraction injury of the thoracic spine. Report of two cases.

PMID- 8150831
TI  - Aneurysmal bone cyst of the thoracic spine: radical excision with use of the
      cavitron. A case report.

PMID- 8150832
TI  - The patellofemoral joint in total knee arthroplasty.

PMID- 8150833
TI  - The use of lasers in orthopaedic procedures.

PMID- 8150834
TI  - The use of lasers in orthopaedic procedures.

PMID- 8150835
TI  - Burn-induced alterations in vasoactive function of the peripheral cutaneous
      microcirculation.
AB  - Alterations in the cutaneous vasomotion function caused by scald burns to a large
      area on the flank were observed and quantified in a dorsal skin flap window with
      a hamster model. Subsequent to chronic implantation of the window chamber to
      provide direct microscopic observation of blood flow for an entire thickness of
      skin, control measurements of vasoactivity in a defined network of arterioles
      were taken by means of a digital video image splitter over a period of several
      days. A 100 degrees C, 5-second water scald was then effected over 17% to 55% of
      the total body surface area, and the vasoactivity was remeasured in the targeted
      set of sites at serial time intervals for 2 to 4 days. Data were acquired
      directly into a computer and analyzed for both the magnitude and time pattern of
      diameter fluctuations during 3-minute observation periods. Average and standard
      deviations of diameters were computed, and the Prony power spectral analysis
      method was applied to identify the presence and strength of fluctuation
      frequencies. In general, vasomotion was suppressed for several hours subsequent
      to the burn, and the activity was dominated by much slower contractions than
      control. No direction of vessel diameter changes prevailed uniformly throughout
      the peripheral microcirculation. Large alternate constrictions and dilations were
      also observed for some arteriolar and venular components, but others exhibited no
      significant change at all. The incidence and magnitude of peripheral
      microvascular response was proportional to the size of the injured area.

PMID- 8150836
TI  - Collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver
      sulfadiazine cream in partial-thickness burns: a pilot study.
AB  - A multifaceted approach that involves early debridement and control of infection
      is critical to successful and rapid burn wound healing. This pilot study was
      conducted in 15 adult patients with burns to assess the usefulness of early
      enzymatic debridement with a combination of collagenase ointment and polymyxin B
      sulfate/bacitracin spray versus silver sulfadiazine cream in partial-thickness
      burns. Combination treatment with collagenase and polymyxin B sulfate/bacitracin
      resulted in significantly shorter time to achieve a clean wound bed than silver
      sulfadiazine (median 6 vs 12 days; p = 0.0012) and significantly more rapid wound
      healing than silver sulfadiazine (median 10 vs 15 days; p = 0.0007). These
      results are encouraging and justify implementation of a larger, multicenter,
      comparative study.

PMID- 8150837
TI  - Aggressive wound closure for elderly patients with burns.
AB  - Elderly patients with burns who were age 70 years or older and who were admitted
      to Tokyo Medical College Hospital from 1981 to 1992 were evaluated. Among 63
      patients with burns, operations were performed in 35. Of the 63, 18 patients died
      (six after operation). Aggressive surgical wound closure with dermolipectomy,
      which we have been performing since 1986, obtained statistically significantly
      earlier wound closure compared with conventional methods. In cases with a burn
      index of 10 to 30, the number of fatalities was significantly lower. In addition,
      the lowering of the ability of daily life and mental status after the wound
      closure was statistically and significantly smaller. From these facts, aggressive
      wound closure with dermolipectomy appears appropriate for elderly patients with
      burns.

PMID- 8150838
TI  - The hemostatic effect of fibrin glue on graft donor sites.
AB  - One of the main uses of topical fibrin glue is hemostasis. Fibrin glue from
      pooled human plasma has been used in Europe for many years. It was used for
      fixation of skin grafts as early as 1944. Because of the risk of hepatitis and
      now of acquired immunodeficiency syndrome, this compound has not been approved by
      the U.S. Food and Drug Administration for use in the United States. It is now
      possible to make fibrin glue from a single unit of blood. Many blood banks have
      this capability, and burn centers in the United States are beginning to report
      its use in skin grafting procedures performed on patients with burns. In an
      effort to document a hemostatic effect, a prospective double-blind study was
      designed. Donor sites of patients with burns undergoing skin grafting were
      studied to provide a uniform wound; anatomic location varied, particularly with
      respect to gravity. Half of each donor site was sprayed with thrombin and fibrin
      glue, and the other half was sprayed with thrombin and placebo. A large absorbent
      pad was placed over the gauze dressing, and all dressings were collected and
      weighed by the investigators at 6 and 18 hours after the operation. Ten patients
      have been studied to date. In five patients slightly more bleeding occurred in
      the site treated with fibrin. One patient had no difference, and four had
      slightly less bleeding on the donor site treated with fibrin. No significant
      difference could be found in this initial study group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8150839
TI  - The effect of mechanical compression on chronic hand edema after burn injury: a
      preliminary report.
AB  - Chronic hand edema after wound healing is a troublesome condition to treat in
      patients with burns. Stagnant edema can cause fibrosis, which impedes
      rehabilitation and may lead to deformity. Although favorable results have been
      reported with mechanical compression used in acute injuries, no literature was
      found on the effects of compression for the treatment of chronic hand-burn edema.
      Five male patients with nine chronically edematous burned hands were subject to
      mechanical compression at 55 mm Hg pressure. A single-cell unit was used for a 30
      minute treatment at 4:1 treatment ratio. Goniometric and volumetric hand
      measurements were recorded both before and after treatment. Although patients
      expressed a subjective feeling of improvement, no statistical difference was
      found in finger joint range of motion nor in hand volume when comparing
      pretreatment and posttreatment measurements. Many different treatment protocols
      exist in the literature and are discussed.

PMID- 8150840
TI  - The use of expanded polytetrafluoroethylene gloves for care of upper-extremity
      burns.
AB  - The combination of a glove made of an expanded polytetrafluoroethylene membrane
      based laminate and silver sulfadiazine cream was evaluated as a treatment for
      burned hands. Eight patients who had burns averaging 25% total body surface area
      and who had 11 extensive partial thickness hand burns (2% total body surface
      area) were treated with an average of 17 gloves over 9 days. The burn wounds
      healed with no unusual or unexpected outcomes. Nurses and therapists agreed that
      dressing changes were quick and easy and that the gloves provided greater range
      of motion and function in the hands. Patients also expressed a preference for
      this method of treatment.

PMID- 8150841
TI  - Blood use in the burn unit: a possible role for erythropoietin.
AB  - Recently, several of our patients have raised questions concerning the safety of
      blood transfusions and especially the transmission of human immunodeficiency
      virus infection. We have noticed a growing reluctance of patients to receive
      blood transfusions. This prompted us to review the use of blood in our burn unit
      for 530 patients who were admitted from 1987 to 1989. Our traditional reasons for
      transfusion have been either an ongoing hemorrhage that leads to hypotension or a
      hematocrit of less than 30%. For these reasons 131 (24.7%) of the 530 patients
      reviewed required transfusions. The average number of units transfused in
      patients who received blood was 10 (range 1 to 69). Three hundred ninety-nine
      patients (75.3%) did not require transfusions. We undertook a prospective
      preliminary trial of recombinant erythropoietin in five patients who were
      admitted to our burn unit over a 2-month period to evaluate whether this agent
      could lessen the transfusion requirements. Because no definite value is given in
      the literature as to what level of hematocrit is most appropriate for
      transfusion, we chose a hematocrit of 20% as our new indication for transfusion.
      Inclusion into the trial required a total body surface area burn of over 10% that
      required at least one operation. Five patients met the inclusion criteria.
      Administration of erythropoietin was started on admission. According to our new
      criteria for transfusion none of the five patients receiving erythropoietin
      required the transfusion of blood or blood products. This study would suggest the
      need for both a prospective clinical trial of erythropoietin and further studies
      to better define the indications for transfusions in patients with burns.

PMID- 8150842
TI  - Successful use of recombinant human erythropoietin in a Jehovah's Witness with a
      thermal injury.
AB  - Options for treating the Jehovah's Witness with burns who repeatedly refuses
      blood are very limited. This article describes the use of human recombinant
      erythropoietin as an alternative to blood transfusion in a Jehovah's Witness with
      a 35% total body surface area burn. The combination of erythropoietin treatment,
      limited blood drawing, and excision and grafting under tourniquet control allowed
      this patient to undergo successful burn care, including four operative procedures
      to excise and graft 19.5% of the body surface area.

PMID- 8150843
TI  - Cyanide poisoning in victims of fire: analysis of 364 cases and review of the
      literature.
AB  - Cyanide is produced by the combustion of natural and synthetic materials. It is
      assumed that cyanide poisoning is a major component of smoke inhalation injury;
      however, scientific verification of this assumption is lacking. In this study we
      examined blood carboxyhemoglobin and cyanide levels in fire fatalities.
      Carboxyhemoglobin levels of 433 fatalities averaged 44.9% and exceeded fatal (>
      or = 50%) levels in 195 cases. Cyanide levels of 364 fatalities averaged 1.0 mg/L
      and exceeded fatal levels (> 3 mg/L) in 31 cases. For victims with cyanide levels
      above 3 mg/L the mean carboxyhemoglobin level was 62.5%. Cyanide poisoning is
      infrequent in fire fatalities, and when present it is associated with significant
      carboxyhemoglobinemia. Cyanide can be both produced and degraded in blood and
      tissue, making interpretation of blood levels difficult. In survivors of fire,
      detoxification of cyanide can occur without specific antidotes with the use of
      aggressive supportive care. Specific assay and treatment for cyanide poisoning is
      rarely necessary in the treatment of victims of smoke and fire.

PMID- 8150844
TI  - Photographic measurement of volar forearm skin movement with wrist extension: the
      influence of elbow position.
AB  - An important function of skin is to allow joint range of motion to occur. An
      assumed clinical relationship exists between joint movement and skin pliability.
      The purpose of this research was to document skin movement of the forearm and
      wrist with photography, to quantify the amount of skin movement during wrist
      extension, and to investigate the influence of elbow positions on forearm skin
      movement. Twenty volunteers had markings placed on the skin of the volar forearm.
      Each subject performed the motion of wrist extension in two elbow test positions
      of flexion and extension. Photographs were taken of the skin markings at the
      beginning and end of wrist extension. A significant difference was found in the
      amount of forearm skin movement that occurred when the elbow was extended and
      flexed (p < 0.001). These results substantiate the use of multijoint range of
      motion during burn rehabilitation.

PMID- 8150845
TI  - Parental well-being and behavioral adjustment of pediatric survivors of burns.
AB  - Parents of pediatric patients with burns often perceive their children as
      troubled and having an increased number of problem behaviors. This study examines
      the relationship between these problem behaviors and the parent's own emotional
      well-being. Mothers of 38 burned children completed three standardized
      questionnaires: Child Behavior Checklist, Parental Stress Index, and the Eight
      State Questionnaire. The population was further divided into troubled and
      untroubled by a Child Behavior Checklist total problem T score of 60. Parents
      were not significantly different from reference populations on most of the
      scales. However, the Parental Stress Index results revealed that parents who
      report their children as troubled are themselves stressed, not only by their
      children's behaviors but in areas unrelated to their children. In addition, these
      mothers report often feeling depressed and guilty on the Eight State
      Questionnaire. This study emphasizes the need for psychological assessment of
      both parents and children.

PMID- 8150846
TI  - Experience with silastic gel sheeting in pediatric scarring.
AB  - Silicone gel sheeting was applied to five hypertrophic scars on five pediatric
      outpatients at an acute care pediatric hospital. After silicone gel application,
      three of the five scars showed initial positive results including reduction in
      the scar size, reduction in the scar thickness, softening of the scar, a decrease
      in vascularity of the scar, and more uniform pigmentation. Many negative results
      including rash, skin breakdown, cessation of scar responsiveness, problems with
      the gel sheet application, and poor durability were documented. Preliminary
      results indicate that topical silicone gel application is not a viable treatment
      option for the control of hypertrophic scarring with a pediatric population.

PMID- 8150847
TI  - Evaluation of topical therapeutic ultrasound to improve response to physical
      therapy and lessen scar contracture after burn injury.
AB  - This study compared results of patients who received standard burn physical
      therapy and topical ultrasound with patients who received standard care alone to
      investigate the effect of topical therapeutic ultrasound on range of motion and
      pain in patients with burns. Fourteen burned extremities were studied. Eight
      joints were randomized to treatment with ultrasound followed by 10 minutes of
      passive stretching. Six joints received placebo ultrasound treatments and
      stretching. All treatments were performed every other day throughout a 2-week
      study period. Joint range of motion was measured before and after each treatment,
      and patients estimated the pain of the procedure. Patients and therapists were
      blinded to the treatment group. Analysis of the data revealed no differences in
      range of motion or perceived pain between the two groups. The effect of
      ultrasound on range of motion and pain was not predictable. We conclude that
      patients are not likely to improve from ultrasound treatment at our protocol
      parameters.

PMID- 8150848
TI  - The nurse's role in end-of-life decisions.
AB  - Last year the American Nurses Association (ANA) published four position
      statements on dealing with end-of-life issues in an effort to guide nurses
      enacting their roles as advocates for dying patients. The following is a brief
      summary of these statements.

PMID- 8150849
TI  - The burn as a continuous traumatic stress: implications for emotional treatment
      during hospitalization.
AB  - Relating to the patient with burns as being posttraumatic calls for specific
      guidelines in emotional therapy. But it seems that burn injury differs from other
      posttraumatic situations in that it confronts the patient with a much more
      complex situation, including not only the actual burn experience but also the
      ensuing difficult period of hospitalization and the subsequent renewed encounter
      with the social environment. That is why we see the patient with burns as
      suffering from a Continuous Traumatic Stress Disorder rather than from a
      Posttraumatic Stress Disorder. Although both disorders confront the patient with
      the same symptoms and with the experience of shattering the stimulus barrier and
      that of the basic assumptions, like the concept of self, invulnerability, and the
      world, they still differ in duration of the trauma. This calls for "dos and
      don'ts" as treatment principles at the time of the hospitalization, which help
      the patient's ability in coping with the continuous trauma.

PMID- 8150850
TI  - Conceptual development of nurse-physician collaboration.
AB  - The concept of nurse-physician collaboration has significance in today's changing
      health care environment. Two camps' views concerning nurse-physician
      collaboration are presented. Camp I supports nurse-physician collaboration using
      four indicators: (1) mutual power-control, (2) separate and combined practice
      spheres, (3) mutual concerns, and (4) common patient goals. Camp II takes a
      totally different approach and describes the structure that must be present
      before collaboration may exist. The literature supports the use of both camps'
      views in developing measures for the concept of collaboration. Once these aspects
      of collaboration can be accurately measured then recommendations can be made
      concerning changes needed in health care delivery systems to effect outcomes.

PMID- 8150851
TI  - A collaborative interaction model and the implementation of shared governance.
AB  - Practical experiences and examples in redesigning the professional nurse's work
      environment are shared. A collaborative interaction model where each nurse was an
      active participant in decision making was developed to convert a nursing unit to
      a shared governance structure. The implementation strategy consisted of self
      assessment for all levels of nurses involved, team building, communication, and
      change. Resulting role transitions that leaders and staff experienced are
      discussed.

PMID- 8150852
TI  - The role of the nurse manager in creating an environment for collaborative
      practice.
AB  - The role of the nurse manager is pivotal in creating a work environment in which
      nurse-physician collaboration is the expected norm. It is the nurse manager who
      clarifies the vision of collaboration, practices as a role model for
      collaboration, and inspires others to achieve this difficult goal. In addition,
      the nurse manager manipulates the environmental resources and facilitates self
      confidence of staff. The management paradigm that unites the work environment
      with individual ability is most likely to facilitate collaborative practice.

PMID- 8150853
TI  - Developing a collaborative professional role for the staff nurse in a shared
      governance model.
AB  - A shared governance model in a nursing division, incorporating a total quality
      management approach, indicates positive outcomes. The model is illustrated in the
      emergency department. The approach to developing the shared governance model and
      a leadership development model are described.

PMID- 8150854
TI  - Nurse-physician collaboration: a descriptive study.
AB  - The purpose of this research was to investigate the nature of nurse-physician
      collaboration using four indicators (power-control, practice spheres, concerns,
      and goals) in a random mail survey of registered nurses (N = 59) and physicians
      (N = 67) in a midwestern metropolitan county. Subjects completed a nurse or
      physician communication scale, an adaptation of the Weiss and Davis Collaborative
      Practice Scales, a practice spheres, and a goals checklist. Nurses and physicians
      were homogeneous on the power-control indicator, (chi 2 = .3(3), p = .98) and
      concern indicator (chi 2 = 7.2(4), p = .13). Nurses and physicians were
      inconsistent in their perceptions of responsibilities for practice spheres and
      patient goals. Relationships of demographic variables to collaboration indicators
      supported profiles of nurses and physicians who may be less collaborative.

PMID- 8150855
TI  - Same place, different experience: nurses and residents on pediatric emergency
      transport.
AB  - A questionnaire was mailed to nurse transport coordinators at the 76 United
      States pediatric training programs listing 35 pediatric residents or more, and a
      related but different questionnaire was mailed to chief pediatric residents at
      the same centers. Comparisons of responses to a series of questions on the role
      of the nurse on transport suggest that the pediatric emergency transport team
      offers an excellent opportunity to implement collaborative practice strategies
      between nurses and residents. Both groups stated the value of professional
      discussion and consultation to derive mutually satisfactory resolutions to
      patient care issues. Physician respondents indicated a genuine respect for the
      nurses' skill and expanded role in the care of critically ill children during
      transport. The transport experience offers a window of opportunity for nurses and
      physicians interested in developing research and practice models aimed at
      fostering collaboration between nurses and physicians-in-training.

PMID- 8150856
TI  - Collaboration in distance education between nursing schools and hospitals.
AB  - Interactive television (ITV) is being used by increasing numbers of nursing
      schools and hospitals to provide educational access to geographically diverse
      learners and nurse employees. ITV-related research suggests that learner outcomes
      and satisfaction with such distance education courses are similar to those
      associated with the traditional classroom. The authors conducted an evaluation of
      a major nursing school's nursing telecourse program (NTP) to assess collaborative
      efforts with hospitals and regional campuses. The respondents, 15 site
      coordinators, were generally satisfied with the operational aspects of the NTP.
      Concerns raised by respondents included classroom space availability, operational
      costs, library resources, and communication equipment and processes. These
      stakeholders' perspectives were viewed as valuable in identifying problems and
      making improvements in the school's NTP.

PMID- 8150857
TI  - A faculty-practice program: three perspectives.
AB  - An urban school of nursing and a 631-bed acute care teaching facility, two
      independent organizations, created a faculty-practice program in 1990 modeled
      after one at Cedar Crest College, Allentown, Pennsylvania. Currently there are
      two full-time faculty joint appointees on 12-month contracts: an Associate
      Director for Nursing Research/Clinical Nurse Researcher (CNR) and an Associate
      Director for Nursing Administration. The benefits and challenges of the faculty
      practice appointments are explored from three viewpoints: those of the (1) Chief
      Nurse Executive of the medical center, (2) the Dean of the School of Nursing, and
      (3) the Joint Appointee, Associate Director for Nursing Research. The joint
      appointee also describes the roles and functions inherent in the joint appointee
      role, for example, researcher, teacher, consultant, collaborator, and grant
      writer. Position descriptions for each joint appointment are included.

PMID- 8150858
TI  - Multidisciplinary teams in the acute care setting.
AB  - The culture of organizations is described based on their goal directedness, human
      resource perspective, political interests, and values and beliefs of the members.
      Based on these descriptions, a generic process for building multidisciplinary
      teams in any hospital setting is discussed. The process includes an in-depth
      organizational analysis and six-step action plan.

PMID- 8150859
TI  - Assay of urinary 2,3-dinor-6-oxo prostaglandin F1 alpha by gas chromatography
      tandem mass spectrometry.
AB  - Prostacyclin (PGI2), an important determinant of cardiovascular biology, is
      produced from arachidonic acid by endothelial cells. Measurement of its stable
      urinary metabolite, 2,3-dinor-6-oxo prostaglandin F1 alpha (PGI2-M), is the
      approach of choice to assess variations of the endogenous synthesis of PGI2 that
      occur in response to dietary, pharmacological and pathological alterations. We
      developed a relatively simple stable isotope dilution assay for PGI2-M which
      involves solid-phase extraction of 10 ml of urine with Chem Elut disposable
      columns, water/solvent partitioning from basic and acidic environments with ethyl
      acetate and methylene chloride, derivatization to 1-pentafluorobenzyl ester
      followed by TLC, methoximation and trimethylsilylation. Quantification was
      achieved, for the first time for PGI2-M, by capillary GC-electron capture
      negative ion MS-MS with a triple quadrupole mass spectrometer operated in the
      negative ion detection mode with methane as moderating gas. The mean inter-assay
      R.S.D., determined on 12 different urine samples, was 5.1 (range 0.4% to 10.5%).
      The excretion of PGI2-M in 34 healthy male subjects (age 26 to 57) was 156.2 +/-
      65.2 (mean +/- S.D.) ng/24 h.

PMID- 8150860
TI  - Determination of fatty acid and triacylglycerol composition of human very-low
      density lipoproteins.
AB  - The fatty acid composition of human very-low-density lipoproteins (VLDL) was
      studied in a population from western Andalusia with a diet in which the fat
      content came mainly from olive oil. The lipid composition of VLDL, including the
      fatty acid composition of the phospholipids and triacylglycerols, was examined by
      capillary gas chromatography. Twenty-five peaks were resolved, ranging in chain
      length from 14 to 24 carbon atoms, including geometric and positional isomers.
      The major fatty acids present in phospholipids were 16:0, 18:0, 18:1(n - 9) and
      18:2(n - 6), and in triacylglycerols were 18:1(n - 9), 16:0 and 18:2(n - 6). The
      major triacylglycerol was POO, followed by PLO and OOO. MLP, PPS and LLL were
      absent. The presence of a large amount of OOO in this fraction demonstrates that
      the triacylglycerol composition of the VLDL depends on the type of diet consumed.

PMID- 8150861
TI  - Improved method for the routine analysis of acetylcholine release in vivo:
      quantitation in the presence and absence of esterase inhibitor.
AB  - An improved high-performance liquid chromatographic (HPLC) method using
      electrochemical detection (ED) is described capable of routinely measuring the
      low levels of acetylcholine (ACh) typically found in rat brain microdialysis
      samples. Microdialysis was performed in the striatum of the urethane anesthetized
      rat using a 4-mm membrane length, high recovery (40% at 1.0 microliters/min;
      ambient conditions), loop-design probe perfused with an artificial cerebrospinal
      fluid (aCSF) solution containing physiologically normal calcium levels (1.2 mM).
      The HPLC method utilizes a polymeric stationary phase to resolve choline (Ch)
      from ACh. These analytes are then converted to hydrogen peroxide (H2O2) by a
      solid-phase reactor (containing immobilized choline oxidase and
      acetylcholinesterase enzymes). The H2O2 is detected amperometrically and
      quantitated on a platinum (Pt) working electrode (+300 mV; with a unique
      analytical cell featuring a solid-state palladium reference electrode). Two
      designs of the Pt working electrode were examined, differing only in the support
      material used (Kel-F or PEEK). The Kel-F/Pt electrode had a limit of detection
      (LOD) for both analytes of < 30 fmol per 10 microliters with a signal-to-noise
      ratio of 3:1. Striatal microdialysis perfusates were monitored for ACh and Ch
      over a 0-1000 nM range of neostigmine (NEO) in the CSF perfusion medium. Using
      the 4-mm probe, basal ACh and Ch levels were detected with a NEO level as low as
      10 nM and were found to be 37 +/- 3 fmol and 22 +/- 1 pmol per 10 microliters
      (mean +/- S.E.M., n = 6 replicates) respectively. In similar experiments using 3
      mm concentric probes comparable (lower) levels of ACh were found with the 50 and
      1000 nM NEO doses (n = 4-21 animals). ACh could not be reliably quantitated when
      animals were perfused with the 10 nM dose of NEO (n = 4). The PEEK/Pt electrode
      had an improved LOD of < 20 fmol per 10 microliters due to a two- to three-fold
      decrease in the background noise component. Basal striatal levels of ACh in the
      absence of NEO approached the LOD and were found to be 15 +/- 2 fmol per 10
      microliters; Ch was 5 +/- 1 pmol per 10 microliters (n = 2, mean of five basal
      samples). The analytical system requires very little maintenance; a simple
      electrochemical electrode cleaning step eliminates the need for routine polishing
      of the Pt electrode and the mobile phase is stable for up to one week.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8150862
TI  - Separation of neutral oligosaccharide alditols from human meconium using high-pH
      anion-exchange chromatography.
AB  - Neutral reduced oligosaccharides are in general not sufficiently retained to
      achieve adequate separation and reproducible chromatography using high-pH anion
      exchange chromatography. We describe a method to increase the retention using two
      columns in series. This method has been applied to the separation of
      oligosaccharides purified from human meconium glycoproteins, obtained as their
      alditols after alkaline-borohydride release of oligosaccharides. The neutral
      oligosaccharide alditols were significantly retained upon two CarboPac PA-100
      columns, connected in series, and eluted in 80 mM sodium hydroxide between 4 and
      10 min. Three sialylated alditols studied were substantially retained and could
      be eluted in a gradient of 0-500 mM sodium acetate-80 mM sodium hydroxide between
      10 and 45 min. The elution patterns were based on their size, charge and linkage,
      such that oligosaccharide alditol isomers could be separated.

PMID- 8150863
TI  - Quantitation of monohydroxy fatty acids by high-performance liquid chromatography
      with fluorescence detection.
AB  - A high-performance liquid chromatographic (HPLC) procedure for the separation of
      hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecanoic acids (HODEs) after
      derivatization of the hydroxy group with 1-anthroylnitrile is described. Anthroyl
      esters of HETEs were separated from those of HODEs by reversed-phase HPLC. The
      positional isomers of the HETEs and HODEs were well separated by normal-phase
      HPLC. The fluorimetric HPLC method has a high sensitivity and naturally occurring
      HETEs can be quantitatively analyzed at the picomolar level. The amount of 5-HETE
      in A23187-stimulated polymorphonuclear leukocytes (PMNLs) was determined by the
      present method. PMNLs produced approximately 150 ng of 5-HETE per 10(7) cells at
      5 min stimulation. The amount of 5-HETE determined by fluorimetric detection was
      consistent with that determined by ultraviolet detection (235 nm).

PMID- 8150864
TI  - Simultaneous determination of hydroperoxides of phosphatidylcholine, cholesterol
      esters and triacylglycerols by column-switching high-performance liquid
      chromatography with a post-column detection system.
AB  - A method for the simultaneous determination of hydroperoxides of
      phosphatidylcholines (PC), triacylglycerols (TG) and cholesterol esters (CE) has
      been developed. A sample was separated into a combined TG and CE hydroperoxides
      fraction and a PC hydroperoxides fraction on a short silica column. The fractions
      were introduced into an ODS column and another silica column by a valve-switching
      device. The PC hydroperoxides were monitored by a post-column detection system
      with diphenyl-1-pyrenylphosphine, and the TG and CE hydroperoxides were monitored
      by another switching device. With this system, the hydroperoxides were determined
      at the picomole level within 32 min. Their detection limits were 2-4 pmol at a
      signal-to-noise ratio of 3, and the relative standard deviations of the peak
      areas were 1.6-3.1%. This method was successfully applied to determine lipid
      hydroperoxides in human plasma.

PMID- 8150865
TI  - Gas chromatographic determination of inorganic tin in rat urine after a single
      oral administration of stannous chloride and mono-, di-, and triphenyltin
      chloride.
AB  - A method is described for the determination of inorganic tin by gas
      chromatography with flame photometric detection. The inorganic tins, stannous and
      stannic, were extracted with hydrochloric acid and n-hexane-benzene in the
      presence of 0.05% tropolone, and both inorganic tins were pentylated to
      tetrapentyltin with a Grignard reagent prior to gas chromatography. The absolute
      limit of detection for tetrapentyltin was 3 pg as tin. The recovery of stannous
      chloride added to rat urine samples was 80.2 +/- 2.4% (mean +/- S.D., n = 8). The
      application of this method to the study of urinary excretion of inorganic tin and
      organotin compounds in rats following oral administration of tin compounds is
      presented. The urinary excretion of tin compounds was observed over a period of
      96 h following administration of stannous chloride or phenyltin compounds. Most
      of the inorganic tin was excreted into urine within 24 h after administration of
      stannous chloride. In the experiments on organotin administration, the level of
      the excretion as total tin for monophenyltin reached a maximum ca. 0-24 h after
      administration, whereas the maxima for di- and triphenyltin were found after 24
      48 h and 48-72 h, respectively. The predominant excretion product of these tin
      compounds found in urine was monophenyltin.

PMID- 8150866
TI  - Chiral high-performance liquid chromatography and gas chromatography of the
      stereoisomers of hexyl 2,5-dichlorophenyl phosphoramidate.
AB  - O-Hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP) is a chiral organophosphorus
      compound that undergoes enzymatic hydrolysis in the rat and hen. Studies of the
      stereospecificity of its biodegradation are necessary to establish HDCP toxicity.
      To this effect, methods have been developed for the analysis of the HDCP
      stereoisomers by gas chromatography (GC) and high-performance liquid
      chromatography (HPLC). The best resolution and analysis were obtained by HPLC
      with UV detection, a OA-4100 Techocel chiral column and the mobile phase: hexane
      1,2-dichloroethane-ethanol (92:5:3, v/v/v). The detection limit was 25 microM for
      HDCP and 5 microM for one of its hydrolytic products: 2,5-dichlorophenol (DCP).
      The method was reproducible intra o inter die. Moreover, a method is described
      for the liquid extraction of HDCP and DCP with 1,2-dichloroethane in biological
      samples, with a yield of (80.3 +/- 9.7)% (n = 10, S.D.) for HDCP and (84.1 +/-
      10.0)% (n = 10, S.D.) for DCP. The method is compared with the solid-phase
      extraction technique with C18 sorbent. The hydrolysis of HDCP by hen plasma is
      studied.

PMID- 8150867
TI  - Evaluation of capillary supercritical fluid chromatography with mass
      spectrometric detection for the analysis of a drug (mebeverine) in a dog plasma
      matrix.
AB  - Supercritical fluid chromatography with mass spectrometric detection was
      evaluated as a technique for the analysis of drugs in biological fluids. Dog
      plasma was spiked with a model drug, mebeverine, and with a deuterium-labeled
      analog of mebeverine. The spiked plasma was prepared for analysis by solid-phase
      extraction on octadecylsilane cartridges. Mebeverine levels in the spiked dog
      plasma samples were determined by interpolation from a standard curve. Accuracy
      and precision of the analysis were determined within and between days. In
      general, accuracy was found to be 100 +/- 15% for plasma samples spiked with 6 to
      60 ng mebeverine/ml. The relative standard deviation for replicate sample
      analysis over this concentration range was between 5 and 12.5%.

PMID- 8150868
TI  - Determination of the aza alkyl lysophospholipid 3-methoxy-2-N,N
      methyloctadecylaminopropyloxyphosphorylcholine in rat plasma by liquid
      chromatography-particle beam-mass spectrometry.
AB  - A sensitive and specific method for the determination of the aza alkyl
      lysophospholipid (AALP) 3-methoxy-2-N,N
      methyloctadecylaminopropyloxyphosphorylcholine (I) in rat plasma is described.
      The target molecule was analyzed by high-performance liquid chromatography (HPLC)
      mass spectrometry (MS) after one single liquid-liquid extraction with chloroform
      methanol (2:1, v/v). 1,2-Didecanoyl-sn-glycero-3-phosphocholine was used as
      internal standard. HPLC was carried out using a polymeric reversed-phase column;
      the coupling to the mass spectrometer was a particle beam (PB) interface, and the
      ionization method was electron impact (EI). This simple and rugged method permits
      the measurement of I in rat plasma in the range of 25 ng/ml-5 micrograms/ml with
      good accuracy and precision and is used in pharmacokinetic studies.

PMID- 8150869
TI  - Simultaneous determination of felbamate and four metabolites in rat cerebrospinal
      fluid by high-performance liquid chromatography.
AB  - An isocratic liquid chromatographic method for direct sample injection has been
      developed for the quantitation of felbamate and four metabolites in rat
      cerebrospinal fluid. The method uses 0.050- or 0.025-ml aliquots of cerebrospinal
      fluid diluted with equal volumes of internal standard. Chromatography is
      performed on a 150 mm x 4.6 mm I.D. Spherisorb ODS2, 3-microns HPLC column eluted
      with a phosphate buffer-acetonitrile-methanol (820:120:60, v/v/v) mobile phase
      and ultraviolet absorbance detection at 210 nm. The linear quantitation ranges
      are: felbamate and the 2-hydroxy metabolite 0.195-200 micrograms/ml, the
      propionic acid metabolite 0.195-50.0 micrograms/ml, the p-hydroxy metabolite
      0.781 to 50.0 micrograms/ml, and the monocarbamate metabolite 0.098-50.0
      micrograms/ml.

PMID- 8150870
TI  - Simultaneous determination of felbamate and three metabolites in rat and dog
      plasmas by high-performance liquid chromatography.
AB  - An isocratic liquid chromatographic method employing one extraction step and a
      150 mm x 4.6 mm I.D. Spherisorb ODS2, 3-microns HPLC column using UV-absorbance
      detection at 210 nm has been developed for the quantitation of felbamate and
      three felbamate metabolites in 0.100-ml aliquots of rat and dog plasmas. The
      linear quantitation range in rat plasma is 0.195-200 micrograms/ml for felbamate;
      1.563-200 micrograms/ml for the p-hydroxy metabolite; 0.391-200 micrograms/ml for
      the 2-hydroxy metabolite; and 0.098-200 micrograms/ml for the monocarbamate
      metabolite. The linear quantitation range in dog plasma is 0.195-200
      micrograms/ml for felbamate; 0.781-200 micrograms/ml for the p-hydroxy
      metabolite; 0.195-200 micrograms/ml for the 2-hydroxy metabolite; and 0.098-200
      micrograms/ml for the monocarbamate metabolite.

PMID- 8150871
TI  - Determination of 3'-amino-3'-deoxythymidine, a cytotoxic metabolite of 3'-azido
      3'-deoxythymidine, in human plasma by ion-pair high-performance liquid
      chromatography.
AB  - A sensitive high-performance liquid chromatographic assay has been developed to
      determine the levels of 3'-amino-3'-deoxythymidine (AMT), a cytotoxic metabolite
      of 3'-azido-3'-deoxy-thymidine (AZT, zidovudine), in human plasma. The sample
      pretreatment involved solid-phase extraction using cation-exchange extraction
      columns. Chromatography was carried out on a C8 column, using a mobile phase of
      methanol-0.01 M ammonium acetate (pH 5)-0.25 M sodium dioctylsulfosuccinate
      (60:40:4, v/v/v) and ultraviolet detection at 265 nm. The method has been
      validated, and stability tests under various conditions have been performed. The
      lower limit of quantitation is 5 ng/ml (using 500-microliters human plasma
      samples). The bioanalytical assay has been used for the determination of AMT in
      patients with AIDS who used AZT.

PMID- 8150872
TI  - High-performance liquid chromatographic assay for the measurement of the novel
      microtubule inhibitor 1069C85 in biological tissues and fluids.
AB  - 1069C85 is a novel tubulin binder developed to circumvent the resistance
      associated with the Vinca alkaloids. Cytotoxic activity has been demonstrated in
      vitro against a variety of tumour cell lines, including a variant of the P388
      leukaemia with acquired resistance to vincristine. A phase I clinical trial is
      planned and an assay suitable for preclinical and clinical pharmacokinetics has
      been developed. A high-performance liquid chromatographic (HPLC) assay is
      described which allows measurement of 1069C85 in plasma, urine, and tissue
      samples. The method uses reversed-phase chromatography with isocratic elution and
      detection by fluorescence at 406 nm following excitation at 340 nm. The assay is
      specific, sensitive (limit of sensitivity 0.25 ng/ml) and reproducible
      (coefficient of variation < 5%). The method has been used to study the
      pharmacokinetics of 1069C85 in Balb C mice following a single oral dose of 1
      mg/kg. The maximum plasma concentration was reached 15 min after administration
      and subsequent elimination was slow with a half life of 6.5 +/- 2.2 h. The drug
      remained detectable in plasma, at 1 +/- 0.5 ng/ml, 24 h after this dose. This
      assay will be used to determine the pharmacokinetic profile of 1069C85 in mice
      and in a forthcoming phase I clinical trial.

PMID- 8150874
TI  - High-performance liquid chromatographic determination of pentamidine in plasma.
AB  - This report describes the analysis of pentamidine by isocratic reversed-phase
      high-performance liquid chromatography (HPLC) using a commercially available
      compound (melphalan) as the external standard. Previously described assays use
      ion-pairing HPLC, an internal standard (hexamidine) that is not readily
      available, and require a relatively large sample size. In the present assay,
      pentamidine was extracted from plasma using solid-phase extraction and was
      analyzed using a C18 column and a mobile phase containing 18% acetonitrile, 2%
      methanol, 0.2 M ammonium acetate and 0.5% triethylamine. The identity of the
      eluting peaks was verified using a diode array detector. The extraction yield of
      pentamidine was 82%. The limit of detection was 8.6 ng/ml with a sample size of
      100 microliters. The inter-day and intra-day coefficients of variation ranged
      between 0.3% and 10% with an average of 5%. This method was applied to study the
      pharmacokinetics of pentamidine in rodents.

PMID- 8150873
TI  - Determination of Elsamitrucin (BMY-28090) in plasma and urine by high-performance
      liquid chromatography with fluorescence detection.
AB  - The cytostatic agent Elsamitrucin is a new fermentation product active in a
      variety of in vivo tumor models of murine and human origin. To determine its
      pharmacokinetics during the clinical phase I trial, an HPLC procedure was
      developed and validated. Plasma samples were extracted after addition of the
      internal standard, i.e. the analog Chartreusin. Urine samples were injected
      without extraction of the samples. Because of the wide concentration range of
      Elsamitrucin in the plasma samples two standard curves were used: up to 100 nM
      and from 100-1000 nM. Recoveries of Elsamitrucin from plasma were 87% and 74% for
      concentrations lower and higher than 100 nM, respectively. The detection limits
      were 1 nM in plasma and 7.5 nM in urine at a signal-to-noise ratio of 3. The
      accuracy ranged from 95-107% for plasma and from 96-104% for urine. The within
      day precision was < or = 4.8% and < or = 2.8% in plasma and urine, respectively.
      The between-day precision was < or = 4.4% and < or = 7.1% in plasma and urine,
      respectively. The method proved to be sufficiently sensitive, specific and
      accurate for analysis of clinical samples for pharmacokinetic purposes.

PMID- 8150875
TI  - Analysis of urinary organic acids by liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry.
AB  - We developed a new method for the rapid determination of urinary organic acids
      using liquid chromatography-atmospheric pressure chemical ionization mass
      spectrometry. Mass spectra of authentic organic acids obtained in the negative
      ion mode showed intense [M-H]- ions with some fragment ions. Urine samples of
      patients with methylmalonic aciduria, ornithine transcarbamylase deficiency, and
      phenylketonuria were extracted using anion-exchange columns. The mass
      chromatograms of the extracts showed some dominant peaks of abnormal metabolites
      characteristic of each disorder. This is a useful method for the analysis of
      urinary organic acids for the diagnosis of organic aciduria, because the sample
      preparation is simple.

PMID- 8150876
TI  - Micellar electrokinetic chromatography of hydroxyproline and other secondary
      amino acids in biological samples with laser-induced fluorescence detection.
AB  - Micellar electrokinetic chromatography (MEKC) with laser-induced fluorescence
      (LIF) was used for the rapid and sensitive detection of hydroxyproline in serum
      and hydrolyzed urine that were pre-column derivatized with 9-fluorenylmethyl
      chloroformate (FMOC). The application of the combined o-phthalaldehyde (OPA)/FMOC
      derivatization in MEKC for the selective detection of secondary amino acids in
      biological samples is investigated.

PMID- 8150877
TI  - Rapid determination of sparteine and its metabolites in urine.
AB  - A method is presented for the isolation, separation and determination of
      sparteine and its metabolites in urine. The isolation is based on rapid
      extraction with dichloromethane and pentane in a glass separator. For the
      separation and determination, capillary gas chromatography with nitrogen
      phosphorus detection was used. The recovery of the method ranged from 81.6% to
      94.8%, and the limit of determination varied between 0.2 and 0.5 microgram ml-1.
      For quantification, 17-ethylsparteine was used as the internal standard.

PMID- 8150878
TI  - Determination of polyanionic macromolecules by size-exclusion chromatography.
AB  - This report presents an extension of a method developed for determination of
      dextran sulfate in rat serum. The drug is a negatively charged polysaccharide
      with a molecular mass of 8000. It is fractionated by molecular size and separated
      from serum components by high-performance size-exclusion chromatography.
      Sensitive detection is achieved by the post-column complexation of the analyte
      with 1,9-dimethylmethylene blue (DMMB). A metachromatic complex is formed; the
      absorbance maximum of the complex is shifted from that of the free dye. Various
      glycosaminoglycans and other macromolecular polyanions interact with DMMB.
      Several can be determined using the chromatographic conditions developed for
      dextran sulfate. The method provides a simple procedure for quantitation of these
      compounds. Compared to spectrophotometric assays, less sample preparation is
      required, selectivity is enhanced, and molecular mass information is provided.
      With modification of eluent composition, dye concentration, and detection
      wavelength, the method can be validated for determination of additional
      compounds.

PMID- 8150879
TI  - High-performance liquid chromatographic determination of bupivacaine in plasma
      samples for biopharmaceutical studies and application to seven other local
      anaesthetics.
AB  - A sensitive analytical procedure for bupivacaine dosing in plasma samples by
      reversed-phase high-performance liquid chromatography is described. After a two
      step extraction, the analysis was performed using a C18 column and a mobile phase
      of 0.01 M sodium dihydrogen-phosphate (pH 2.1)-acetonitrile (80:20, v/v). The
      extraction yield of bupivacaine from plasma was 73.5 +/- 5.1% (mean +/- S.D., n =
      10). The within-day and between-day reproducibilities at a concentration of 100
      ng/ml were 2.1% and 5.6%, respectively (n = 10). Calibration curves were linear
      (r2 = 0.9996) between 5 and 1000 ng/ml. The limit of detection, defined by a
      signal-to-noise ratio of 3:1, was 2 ng/ml. The accuracy at a concentration of 100
      ng/ml was 2.3%. This method could be applied to the plasma analysis of seven
      other local anaesthetics (articaine, etidocaine, lidocaine, mepivacaine,
      pramocaine, procaine and tetracaine). The procedure was used in bioavailability
      studies of bupivacaine-loaded poly(D,L-lactide) (i.e. PLA) and poly(D,L-lactide
      co-glycolide) (i.e. PLGA) microspheres after subcutaneous and intrathecal
      administrations in rabbits.

PMID- 8150880
TI  - High-performance liquid chromatographic separation of ondansetron enantiomers in
      serum using a cellulose-derivatized stationary phase and solid-phase extraction.
AB  - R(-)-Ondansetron and S(+)-ondansetron in human serum were resolved and quantified
      using a stereospecific HPLC method. Each enantiomer and the internal standard
      prazosin were isolated from serum using a solid-phase extraction procedure on a
      cyanopropyl column. Recoveries of 97, 96 and 88% were obtained for the R(-)
      enantiomer, the S(+)-enantiomer, and the internal standard, respectively. A
      cellulose-based chiral analytical column (Chiralcel OD) was used with a mobile
      phase consisting of hexane-95% ethanol-2-propanol-acetonitrile (65:25:10:1, v/v).
      Linear calibration curves were obtained for each enantiomer in serum in the
      concentration range 10-200 ng/ml. The limit of quantitation of each enantiomer
      was 10 ng/ml. The detection limit for each enantiomer in serum using UV detection
      at 216 nm was 2.5 ng/ml (signal-to-noise ratio of 3).

PMID- 8150881
TI  - Source memory in mild to moderate Alzheimer's disease.
AB  - This research examined whether source memory is preserved in patients with mild
      to moderate Alzheimer's disease (AD). In Experiment 1, AD patients and normal
      elderly controls recalled true facts (information acquired outside of the
      experimental setting) and made-up facts (information acquired in the experiment),
      and they determined the source of these memories. Relative to controls, AD
      patients recalled fewer facts, but when they remembered this information, they
      attributed their learning to the correct source. In Experiment 2, memory of made
      up facts was equated between groups by incorporating a 1-week recall delay for
      the controls. Again, AD patients accurately determined whether facts were learned
      inside or outside of the experiment. However, both groups performed at chance in
      terms of their memory for whether a made-up fact was read on a card or told by
      the examiner. The findings indicate relative preservation of source memory in the
      earliest stages of AD and are discussed in terms of methodological problems in
      testing source memory in impaired groups and in terms of frontal-lobe
      functioning.

PMID- 8150882
TI  - Allocation of attention to programming of movement sequences in Parkinson's
      disease.
AB  - The allocation of attention to the programming and execution of movement
      sequences was examined in Parkinson's disease (PD). The time taken to initiate
      and execute sequences of one, three, and five button taps was examined, while
      also varying the hand used (left or right) and the attentional resources that
      could be allocated to sequencing (using single- versus dual-task conditions).
      These results showed that performance anomalies in PD were most apparent with the
      preferred right hand under single-rather than dual-task conditions. Subjects
      suffering from PD may tend to divert attention from the right hand under single
      task conditions, and perhaps with short sequences, as well as being less likely
      to prepare sequences of more than three movements in advance with that hand.
      These effects were unlikely to reflect asymmetric pathology. If the right hand of
      such subjects has in some respects now come to behave more like a "clumsy" left
      hand, this may reflect a deliberate strategic choice in an attempt to cope with a
      movement impairment.

PMID- 8150883
TI  - Effect of attentional bias to right space on wheelchair mobility.
AB  - The impact of hemispatial neglect on wheelchair navigation was investigated using
      a wheelchair obstacle course. The results replicated the findings of Webster et
      al. (1988): Right-CVA patients with hemispatial neglect (n = 25) struck more
      objects on their left and ran directly into obstacles placed in their path (p <
      .0001). Right-CVA patients who did not omit left-space targets on letter
      cancellation (n = 23) did not run directly into obstacles; however, they did
      sideswipe more obstacles and struck more left-sided obstacles than did left-CVA
      (n = 20) and nonpatient controls (n = 19; p < .0001). Both hemi-neglecting
      patients and right-CVA patients who committed left-space sideswipes (n = 12)
      evidenced attentional bias to right space, as measured by more rightward starting
      points on letter cancellation and the Rey-Osterreith Complex Figure copy (p <
      .0001).

PMID- 8150884
TI  - Visual event-related potentials of dyslexic children to rhyming and nonrhyming
      stimuli.
AB  - In a visual event-related potential (ERP) study, children diagnosed as dyslexic
      in terms of both age and IQ discrepancy criteria were compared with two contrast
      groups: poor for age (SLOW) readers and normal reading children with Attention
      Deficit Disorder (ADD). The children viewed 200 stimulus pairs and judged whether
      the second stimulus of each pair rhymed with the first. The first stimulus was
      always a three-letter word, while half of the second stimuli were pronounceable
      nonsense words and half were real words. Rhyme probability was 50%. The ERP
      waveforms of the dyslexics were significantly different from those of the ADD
      group in showing less late negativity. The SLOW group's waveforms more closely
      paralleled those of the ADD group. The major anomalous feature of the dyslexics'
      waveform was a pronounced late positive peak (P500), which followed an attenuated
      N450 peak. Over all groups, the N450 peak was sensitive to the rhyme
      manipulation, as has been found in adults (Rugg, 1984a, 1984b). Real words and
      nonsense words produced similar waveforms. Hemispheric effects were found but did
      not interact with group. Results suggest non-automatic visual cognitive
      processing of rhyme in dyslexics.

PMID- 8150885
TI  - Case report of an intracarotid amobarbital procedure performed for a deaf
      patient.
AB  - The intracarotid amobarbital procedure (IAP) was conducted with a profoundly deaf
      young man prior to right anteromedial temporal lobectomy for pharmacologically
      refractory partial complex seizures. The IAP required considerable modification
      in order to take into account the use of varying sign language methods and
      related issues. Visual memory, American Sign Language, signed English, and finger
      spelling functioning were all assessed. The patient manifested left hemisphere
      dominance for all these abilities, performing well under right hemisphere
      anesthesia. In contrast, no ability to function on these tasks was detectable
      when the left hemisphere was anesthetized. This demonstrates that an intact left
      temporal lobe and related structures are sufficient to support sign language
      functioning. The development of a deaf adaptation of the IAP is of methodological
      significance, as the IAP is thereby rendered accessible for deaf patients.

PMID- 8150886
TI  - Multiple comparison methods: establishing guidelines for their valid application
      in neuropsychological research.
AB  - This comment serves to provide a rationale for research clinical
      neuropsychologists to decide: (1) under what conditions multiple comparison
      methods are required; and (2) what specific guidelines can be used to distinguish
      conditions favoring a given multiple comparison technique over its competitors.
      The topic is discussed both for the parametric and nonparametric case, as well as
      for post hoc tests following both statistically significant main effects and
      interactions.

PMID- 8150887
TI  - Handedness is related to formal thought disorder and language dysfunction in
      schizophrenia.
AB  - The handedness of 29 schizophrenics, 42 manic-depressives, and 25 normal controls
      was examined in relation to formal thought disorder and language dysfunction.
      Subjects demonstrated hand preference (Preference Index) and also performed four
      tasks of manual proficiency. On each of the four proficiency tasks a lateral
      proficiency score was computed to quantify direction and degree of manual
      superiority and their mean constituted the Lateral Proficiency Index. A
      Variability Index, consisting of their standard deviation, was also computed.
      Sinistrality, as measured by the Preference Index, was related to severity of
      formal thought disorder in male schizophrenics. The Variability Index was
      significantly related to severity of formal thought disorder and to language
      dysfunction in the schizophrenic group as a whole. These relations were not
      demonstrated in the control groups. These findings support the hypothesis that,
      in schizophrenia, atypical handedness is a marker of left-hemisphere dysfunction
      that also disrupts language processes, including those implicated in the
      manifestation of formal thought disorder.

PMID- 8150888
TI  - Long-term neurobehavioral outcome in pediatric brain-tumor patients: review and
      methodological critique.
AB  - This paper provides an overview of pediatric brain tumors and reviews the
      literature on long-term neurobehavioral outcomes for these children. Progress in
      this area has been slow due to numerous methodological and practical
      complications. While some general conclusions can be drawn, the development of
      comprehensive models awaits more research into the multiplicity of biological and
      nonbiological events, and their interactions, potentially affecting outcome.
      Increased theoretical and methodological sophistication will be needed to address
      this complex classification of diseases. Barriers to research in this area are
      enumerated as are suggestions for future efforts.

PMID- 8150889
TI  - Learning disability subtypes and the effects of auditory and visual priming on
      visual event-related potentials to words.
AB  - Three learning-disability (LD) subtype groups and a normal control group of
      children were compared in their visual event-related potentials (ERPs) to primed
      and unprimed words. The LD subtypes were defined by deficient performance on
      tests of arithmetic (Group A), reading and spelling (Group RS), or both (Group
      RSA). The primed words were preceded by pictures or spoken words having a related
      meaning, while unprimed words were preceded by non-associated pictures or spoken
      words. For normal controls, N450 amplitude was greater to unprimed words than to
      words primed by pictures and spoken words. For Group A, N450 amplitude was
      reduced by spoken-word primes, but not by picture primes, an effect that
      demonstrates a deficit in processing visual-spatial information. For Group RS and
      Group RSA, neither picture nor spoken-word primes reduced N450 amplitude. These
      effects can be understood in terms of deficiencies in processing auditory-verbal
      information. Normal controls displayed a greater left- than right-hemispheric
      asymmetry in frontal N450 amplitude to unprimed words, an effect that is
      consistent with the association of skilled reading with hemispheric
      specialization. This asymmetry was absent in the ERPs of all the LD subtypes. The
      distinct ERP effects for the groups endorses the value of defining LD subtypes on
      the basis of patterns of deficits in arithmetic and reading and spelling.

PMID- 8150890
TI  - Some aspects of memory disorders clearly distinguish dementia of the Alzheimer's
      type from depressive pseudo-dementia.
AB  - Two groups of patients affected by mild dementia of the Alzheimer's type (n = 42)
      or by depressive pseudo-dementia (n = 26) were given a modified version of the
      Rey's Auditory Verbal Learning Test. The two groups were roughly matched for
      overall level of cognitive impairment. The main purpose of the research was to
      determine if some aspects of their memory disorders distinguished the two
      diagnostic groups. Comparison between results obtained on recall and on
      recognition measures was of little diagnostic usefulness in distinguishing
      dementia of the Alzheimer's type (DAT) from depressive pseudo-dementia (DPD). A
      marked prevalence of the recency over the primary effect in immediate recall, a
      high rate of forgetting, and the presence of many intrusion errors on delayed
      recall were observed more frequently in DAT than in DPD patients. None of these
      indices, however, was sensitive and specific enough to allow a confident
      diagnostic discrimination at the individual case level. The memory measure which
      best distinguished DAT from DPD patients was the presence of several false
      positive errors on delayed recognition because DAT patients adopted a very
      liberal response bias, endorsing many false recognition errors, whereas DPD
      patients adopted a conservative criterion and tended to miss real stimuli, rather
      than making false recognition errors.

PMID- 8150891
TI  - Callosal morphology and performance on intelligence tests.
AB  - Variation in the size of the human corpus callosum was examined in relation to
      variation in measured IQ. The midsagittal surface area of the corpus callosum,
      obtained by magnetic resonance imaging, was measured in 47 patients with
      epilepsy. Intellectual ability was positively related to a larger posterior
      callosal area. We suggest that the relationship between the posterior callosal
      region and measured intelligence is "non-functional" in itself, but rather, may
      reflect other anatomical-cognitive associations. That is, differences in splenial
      size may reflect differences in the number of cortical neurons and
      interconnections between areas of the brain that are important for processing the
      kind of information measured on intelligence tests. Our conclusions, however,
      must be tempered by a number of factors; in particular, the nature of our
      subjects and the relatively small sample size.

PMID- 8150892
TI  - Dichotic listening and focused attention in children with hemiplegic cerebral
      palsy.
AB  - Dichotic listening data are reported from children with left and right
      hemiplegia, compared with a normal, age-matched, control group. The dichotic
      listening test was performed under two different attentional instructions. The
      aim of the study was to investigate whether lateral injury to one hemisphere also
      affects the capacity to direct attention in a laterality task because of
      inattention. The dichotic task consisted of consonant-vowel syllables that were
      presented with two different instructions, to attend to the left- or right-ear
      stimulus. The results showed that the control children had a right-ear advantage
      during the forced-right attention instruction, and a small left-ear advantage
      during the forced-left instruction. The two hemiplegia groups, however, showed
      the same ear advantage irrespective of attentional instruction. The results are
      discussed in terms of hemi-inattention and hypoarousal of the lesioned hemisphere
      in children with hemiplegia.

PMID- 8150893
TI  - Development and validation of a Multiple Ability Self-Report Questionnaire.
AB  - We present results from three studies on the development and validation of the
      Multiple Ability Self-Report Questionnaire (MASQ), a self-report measure
      comprising items from five cognitive domains; language, visuo-perceptual, verbal
      memory, visual memory, and attention. In Study 1, we determined the content
      relevance of the questionnaire items. In Study 2, we assessed the basic
      psychometric properties (i.e., internal consistency and test-retest reliability)
      of the MASQ in 118 individuals without neurologic or psychiatric disorder, aged
      25 to 88 years. In Study 3 we provide validity data for the MASQ by comparing the
      ratings of normals to people with unilateral temporal-lobe epilepsy, and
      examining the relationship of self-report to objective test performance. The
      potential use of the MASQ to study the neurologic and psychological correlates of
      accuracy and unawareness in self-appraisal across different cognitive domains and
      various clinical groups is discussed.

PMID- 8150894
TI  - Preliminaries to fertilization. The role of cholesterol during capacitation of
      human spermatozoa.

PMID- 8150895
TI  - Mechanism and control of the human sperm acrosome reaction.

PMID- 8150896
TI  - Gonadotrophin-releasing hormone agonist and ovarian hyperstimulation syndrome in
      assisted reproduction.
AB  - The available literature concerning the association between gonadotrophin
      releasing hormone agonist and ovarian hyperstimulation syndrome has been reviewed
      and the different patterns by which this agent may contribute to the development
      of such iatrogenic complication has been elicited, and guidelines have been
      presented for prevention of this malady. Gonadotrophin-releasing hormone agonist
      acts directly on human granulosa cells, probably in its own dose-dependent
      manner. The extent of this action is probably subjected to follicular maturation
      stage and to the degree of gonadotrophin pre-treatment. Various agonist effects
      in assisted reproduction may be implicated in the development of ovarian
      hyperstimulation syndrome: a higher amount of menotrophin; premature
      luteinization prevention; 'flare-up' effect; and a higher pregnancy rate.
      Different methods for prevention of ovarian hyperstimulation syndrome may be
      attempted: (i) all embryo cryopreservation with luteal phase reinitiation of
      agonist; (ii) avoidance of ovulatory human chorionic gonadotrophin (HCG) and
      continuation of agonist; (iii) cancellation of ovulatory HCG, prolongation of
      agonist and later recommencement of menotrophin; (iv) pre-ovulatory LH surge
      triggering by agonist instead of the conventional HCG. Gonadotrophin-releasing
      hormone agonist may affect the steroidogenic ovarian stroma directly and such
      interaction may aggravate the development of ovarian hyperstimulation syndrome.

PMID- 8150897
TI  - Sperm numbers and distribution within the human fallopian tube around ovulation.
AB  - This study aimed to determine the number and distribution of spermatozoa within
      the human Fallopian tubes around ovulation. Parous women, undergoing total
      abdominal hysterectomy for menorrhagia, were inseminated with either partner's
      semen (3/10) or donor semen (7/10). Approximately 18 h later both Fallopian tubes
      were ligatured into ampullary, isthmic and intramural regions. These were removed
      and assessed for sperm content by flushing, scanning electron microscopy (SEM) or
      homogenization. A median of 251 spermatozoa were recovered (range, 79-1386). The
      number of spermatozoa within each tube was not significantly different. The
      ovulatory ampulla contained a significantly (P < or = 0.01) larger percentage of
      spermatozoa than the non-ovulatory ampulla. The number of motile spermatozoa
      inseminated was not significantly correlated to the number of spermatozoa
      recovered, but a trend was identified. The time between the onset of the
      luteinizing hormone surge and hysterectomy was significantly correlated (P < or =
      0.01) to the number of spermatozoa within the intramural regions, but not to the
      tubal sperm distribution. Spermatozoa were not observed, by SEM, bound to the
      tubal epithelium. These data suggest that, after artificial insemination at
      least, sperm access to the human Fallopian tube may be controlled, but that
      ovulation does not affect the redistribution of spermatozoa between tubal regions
      and that the isthmus does not appear to act specifically as a sperm reservoir.

PMID- 8150898
TI  - Luteal function following ovulation induction in polycystic ovary syndrome
      patients using exogenous gonadotrophins in combination with a gonadotrophin
      releasing hormone agonist.
AB  - The luteal phase was studied in 12 polycystic ovary syndrome (PCOS) patients
      following ovulation induction using exogenous gonadotrophins combined with a
      gonadotrophin-releasing hormone agonist (GnRH-a). Human menopausal gonadotrophin
      (HMG) was preceded by 3 weeks of treatment with GnRH-a (buserelin; 1200
      micrograms/day intra-nasally) and administered in a step-down dose regimen
      starting with 225 IU/day i.m. GnRH-a was withheld the day before administration
      of human chorionic gonadotrophin (HCG; 10,000 IU i.m.). Blood sampling and
      ultrasound monitoring was performed every 2-3 days until menses. The luteal phase
      was significantly shorter in PCOS patients as compared to eight regularly cycling
      controls: 8.8 (3.3-11.4) days [median(range)] versus 12.8 (8.9-15.9) days (P =
      0.01). Median peak values for progesterone did not show significant differences
      comparing both groups: 52.3 (17.1-510.3) nmol/l versus 43.0 (31.2-71.1) nmol/l,
      respectively (P = 0.8). The interval between the day of the progesterone peak and
      return to baseline was significantly shorter in the PCOS patients than in
      controls: 2.5 (0.3-4.9) days versus 4.2 (3.9-10.5) days (P < 0.005). Luteinizing
      hormone (LH) concentrations during the luteal phase as reflected by area under
      the curve were significantly lower in PCOS as compared to controls: 4.4 (1.6
      21.0) IU/l x days and 49.0 (27.8-79.6) IU/l x days, respectively (P < 0.001). In
      conclusion, patients with PCOS may suffer from insufficient luteal phases after
      ovulation induction using HMG/HCG in combination with a GnRH-a. The corpus luteum
      apparently lacks the support of endogenous LH and may be stimulated only by the
      pre-ovulatory injection of HCG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150899
TI  - The induction of ovulation with pulsatile gonadotrophin-releasing hormone (GnRH)
      administration in hyperandrogenic women after down-regulation with buserelin or
      suppression with an oral contraceptive.
AB  - The hypothalamic-pituitary axis of 22 hyperandrogenic infertile women had
      suppression with either the gonadotrophin-releasing hormone (GnRH)-analogue
      buserelin (n = 12) or with an oestrogen-gestagen compound (Diane; n = 12). This
      was followed by pulsatile GnRH application for inducing ovulation (Zyklomat). In
      terms of ovulation and pregnancy rates the buserelin pre-treatment was more
      effective than the steroid pre-treatment, especially in hyperandrogenic non
      polycystic ovaries (PCO).

PMID- 8150900
TI  - von Willebrand factor: an endothelial marker to monitor in-vitro fertilization
      patients with ovarian hyperstimulation syndrome.
AB  - A retrospective study was conducted to evaluate the possible role of endothelial
      and extracellular factors in the pathophysiology of ovarian hyperstimulation
      syndrome (OHSS). Plasma changes in von Willebrand-Jurgen factor were correlated
      with the clinical condition of hyperstimulated patients, since the rise of
      capillary permeability is the central event in all subsequent morbidity. The
      corresponding oestradiol levels and ultrasound parameters were assessed. In-vitro
      fertilization patients designated as 'high responders' and with oestradiol values
      > 2500 pg/ml and > 8 pre-ovulatory follicles at the time of human chorionic
      gonadotrophin (HCG) injection were assessed. Among 62 patients, 37 fulfilled
      these criteria and 18 developed OHSS, indicating the low predictive ability of
      ultrasound and oestradiol values alone. The remaining 19 patients served as
      control group. von Willebrand factor-associated antigen in plasma was measured
      using enzyme-linked immunosorbent assay and ristocetin co-factor activity by an
      aggregatometric test. Basal values of the two groups of patients did not differ
      but there were large inter-individual variations. A slight increase occurred in
      the control group until the day of HCG although individual cycles showed 'no
      change of pattern' or a 'decreasing tendency' from the start. Some patients
      allocated to the non-hyperstimulated type showed a steep increase of values
      followed by a decline. A consistent increase in the OHSS group lasted after
      embryo transfer even to the late corpus luteum phase. These subtle changes of
      capillary permeability or damage always preceded the clinical signs, such as
      ascites, haemoconcentration, hypoproteinaemia and pleural effusion. Mean values
      differed in the two groups from the day preceding ovum retrieval.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8150901
TI  - Daily measurements and in-vitro effects of human chorionic gonadotrophin in the
      early luteal phase.
AB  - The purpose of the present study was to analyse daily measurements of human
      chorionic gonadotrophin (HCG) in in-vitro fertilization (IVF) cycles and to
      reproduce the effects of HCG in vitro using human granulosa-luteinized cells from
      the same patients. The study population consisted of nine women undergoing IVF
      because of tubal infertility in whom blood was drawn every 24 h from the day of
      the ovulatory dose of HCG (10,000 IU) until 6 days after ovum pick-up. Granulosa
      luteal cells from the follicular aspirates were collected and cultured in vitro
      up to 6 days in the presence of increasing concentrations (0, 0.01, 0.1, 1.0 and
      100.0 IU/ml) of HCG. Serum progesterone and HCG in vivo as well as progesterone
      accumulation in vitro on days 2, 4 and 6, were the main outcome measures. Maximum
      HCG concentrations (0.25 IU/ml) were reached the day before ovum pick-up, and
      continuously decreased until day 6 after ovum retrieval. HCG did not stimulate
      progesterone production in vitro at any dose tested until day 6 after ovum pick
      up. Then, 0.01 IU/ml resulted significantly (P < 0.05) stimulatory compared to
      controls, while 1.0 IU/ml was inhibitory (P < 0.05). It is concluded that HCG
      supplementation in an IVF cycle is unnecessary until day 6 after ovum pick-up. On
      day 6, progesterone production is stimulated with very low concentrations of HCG.

PMID- 8150902
TI  - Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation
      in patients undergoing IVF: a randomized comparative study.
AB  - One-hundred women undergoing ovarian stimulation with gonadotrophin-releasing
      hormone agonist (GnRH-a) and a human menopausal gonadotrophin (HMG) for in-vitro
      fertilization (IVF) participated in this randomized comparative study. The
      effectiveness of long-acting s.c. goserelin (Zoladex depot; 49 patients) and
      intranasally (i.n.) administered buserelin acetate (Suprefact; 51 patients) for
      pituitary down-regulation was compared. Treatment with s.c. goserelin (3.6 mg) or
      i.n. buserelin acetate (200 micrograms; 6 times/day) was started on day 21-23 of
      the cycle. Stimulation with 150 IU of HMG/day was started after at least 11 days
      of GnRH-a treatment. There were no differences in the time required for
      follicular development nor in the clinical outcome between groups treated with
      either goserelin or buserelin. The number of oocytes recovered in the goserelin
      group was 6.7 +/- 5.0 versus 6.3 +/- 4.9 in the buserelin group. There were 11
      pregnancies after the use of goserelin (22.4%) and 12 pregnancies in those given
      buserelin (24.0%). The number of HMG ampoules needed for follicular maturation
      was higher in the goserelin group (27.9 +/- 7.8) than in the buserelin group
      (24.6 +/- 7.8, P < 0.05). The patients given buserelin suffered significantly
      more from tiredness, depression, headache and abdominal pain than those receiving
      goserelin, whereas there were no differences between the groups in experiencing
      mental irritability, nausea and swelling. Subcutaneous goserelin depot injection
      offers a useful alternative for pituitary down-regulation in IVF stimulation.

PMID- 8150903
TI  - The combination of gonadotrophin-releasing hormone (GnRH) antagonist and
      pulsatile GnRH normalizes luteinizing hormone secretion in polycystic ovarian
      disease but fails to induce follicular maturation.
AB  - To evaluate the role of altered luteinizing hormone (LH) release in the mechanism
      of polycystic ovarian disease (PCOD) anovulation, we have co-administered a
      gonadotrophin-releasing hormone (GnRH) antagonist and pulsatile GnRH therapy to
      two clomiphene citrate-resistant PCOD patients. The aim was to correct their
      inappropriate gonadotrophin secretion. Nal-Glu was administered s.c. every 72 h
      to both subjects for 3 weeks. On day 7 after commencing the study, intravenous
      pulsatile GnRH therapy was initiated (10 micrograms/pulse) every 90 min for 15
      days to both subjects. In one subject, Nal-Glu treatment was continued and the
      GnRH dose was increased to 20 micrograms/pulse for 10 additional days. Prior to
      Nal-Glu, mean serum LH levels were 10.4 +/- 1.6 and 9.3 +/- 1.3 mIU/ml (mean +/-
      SEM) and mean interpulse intervals were 67.1 and 60 min in patients 1 and 2,
      respectively. Mean serum FSH levels were 4.9 +/- 0.4 and 4.2 +/- 0.2 mIU/ml for
      patients 1 and 2, respectively. LH pulsatility was abolished following Nal-Glu,
      mean serum LH decreased to 1.1 +/- 0.1 and 1.3 +/- 0.5 mIU/ml and mean FSH to 1.8
      +/- 0.1 and 2 +/- 0.1 mIU/ml in the two subjects. On the 4th day of the combined
      therapy, mean serum LH increased to 5.4 +/- 1.3 and 3.9 +/- 0.9 mIU/ml with a
      mean interpulse interval of 72 and 80 min, respectively. Mean FSH levels
      increased to 3 +/- 0.1 and 2.8 +/- 0.1 mIU/ml, respectively and to 5.5 +/- 0.2
      mIU/ml after the GnRH dose was increased in patient 2.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8150904
TI  - Ultrasonic monitoring during replacement of frozen/thawed embryos in natural and
      hormone replacement cycles.
AB  - We evaluated the results of cryopreserved/thawed embryo replacement (FER) to
      determine if the outcome following transfer in a natural cycle in a defined group
      was different to that from a hormone replacement cycle, and also to assess
      vaginal ultrasonographic features that assist in predicting the timing of the
      transfer. At the London Fertility Centre, 149 consecutive FER cycles were studied
      retrospectively. Women with proven ovulation and regular cycles were included
      during natural cycles (n = 77). The hormone replacement cycle group included
      women with anovulation, irregular cycles and older women (n = 72). In the natural
      cycle group, transfer was performed following positive urinary luteinizing
      hormone (LH) surge and confirmation of ovulation by ultrasonography. With the
      hormone replacement therapy group, gonadotrophin-releasing hormone analogue was
      used to induce pituitary down-regulation, oestradiol valerate was supplemented
      followed by regular ultrasound monitoring, and FER 2 days following the
      initiation of progesterone, which was started once adequate endometrial
      development was noticed on ultrasonography. The pregnancy and ongoing/delivery
      rates were analysed in relation to the treatment cycle, age, number and quality
      of embryos transferred. Ultrasonographic features were examined to evaluate their
      relationship with the outcome of treatment. The results showed that no difference
      existed between natural and hormone replacement cycles in pregnancy rates per
      cycle (26 and 25%), ongoing/delivery rate (20.8% in both groups), and
      implantation rate (10.3 and 10.6%). Pregnancy rates were not influenced by the
      number of embryos transferred, stage at which the embryos were cryopreserved, or
      whether they were extra embryos from in-vitro fertilization/embryo transfer, or
      gamete intra-Fallopian transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150905
TI  - Metastatic ovarian strumosis in an in-vitro fertilization patient.
AB  - Malignant struma ovarii is a very rare tumour, with considerable controversy
      concerning the necessary histologic features for malignancy. Still more
      infrequent is the condition termed 'metastatic ovarian strumosis' or simply
      'benign strumosis or strumatosis' and characterized by the presence of peritoneal
      implants of mature thyroid tissue occurring in struma ovarii. 'Strumosis' should
      not be confused with malignancy. Presented is a case of 'metastatic ovarian
      strumosis' in a 36-year-old woman with primary infertility who underwent three in
      vitro fertilization (IVF) cycles with ovarian stimulation. She received hormonal
      treatment for 6 months after her last IVF because of 'persistent enlarged ovarian
      follicles' which were in fact 'thyroid follicles'.

PMID- 8150906
TI  - Ultrastructure of human ovarian primordial follicles after combination
      chemotherapy for Hodgkin's disease.
AB  - Ovarian damage, with consequent permanent infertility, is one of the more common
      side-effects which occurs during chemotherapeutic treatment of patients affected
      by Hodgkin's disease. This damage is morphologically represented by a marked loss
      of primordial and primary follicles. The administration of contraceptive drugs
      before starting chemotherapy enhances survival of a greater number of ovarian
      follicles, as revealed by morphometric analyses, nevertheless, total ovarian
      protection is not assured. This study evaluated the number and the morphology of
      ovarian follicles, by means of transmission electron microscopy, in patients with
      Hodgkin's disease treated with multi-drug chemotherapeutic protocols following
      the administration of medroxyprogesterone acetate. Ovarian biopsies were
      performed prior to any pharmacological treatment, after medroxyprogesterone
      therapy, and after this therapy plus chemotherapy. Particular attention was given
      to the ultrastructure of primordial follicles. After morphometric evaluation,
      primordial follicles were numerous in controls and medroxyprogesterone therapy
      (28.55 +/- 6.59/mm3 of ovarian cortex). After chemotherapy and
      medroxyprogesterone acetate, the number of follicles was slightly reduced (19.37
      +/- 3.41/mm3 of ovarian cortex) in contrast to the dramatic loss usually observed
      when protection is not given, although more follicles were atretic.
      Medroxyprogesterone may protect follicles only from acute, toxic effects of
      chemotherapy, which dramatically reduce their number and lead to sterility.
      Nevertheless, the quality of follicles is still impaired, and many undergo
      atresia, resulting in a shortened fertility period.

PMID- 8150907
TI  - Oocyte donation: comparison between recipients from different age groups.
AB  - Oocyte donation was carried out in 87 patients in 141 replacement cycles. These
      patients received oocytes from 108 women undergoing assisted reproductive
      technology procedures at our centre. Standardized hormonal replacement therapy
      and in-vitro fertilization procedures were performed. We divided recipients into
      four groups according to their age (group A, 21-35 years; B, 36-40 years; C, 41
      49 years; and D, 50-61 years). Oocytes donors were 21-35 years old, and equally
      spread across these different age groups. There were significant differences in
      the pregnancy and implantation rates according to the age of the recipients;
      which were 45% and 23% respectively in women 21-35 years old (group A) versus 23%
      and 10% in women 41-49 years old (group C). A comparison of data between oocyte
      donors and young recipients, with similar results in donors and young recipients,
      with pregnancy rates of 45% and 42% and implantation rates of 23% and 19.5%
      respectively. Statistically significant differences were found between donors and
      the older recipients, pregnancy rates being 43% versus 23%, and implantation
      rates 18% versus 10%. These data seem to demonstrate a lesser likelihood of
      pregnancy and implantation in older recipients because of increasing uterine age.

PMID- 8150908
TI  - A new approach to gamete intra-fallopian transfer via hysteroscopy.
AB  - This study describes the technique and results of a new approach for the
      hysteroscopic catheterization of the Fallopian tube in order to transfer gametes
      (hysteroscopic GIFT). Ovarian stimulation was started on 51 patients. Three
      cycles were cancelled because of a failure of ovarian response. Forty-eight
      patients underwent hysteroscopic GIFT utilizing a technique completely different,
      easier, faster and more precise than that previously reported. Fourteen
      pregnancies were achieved (29.2%) of which five are ongoing, six patients have
      delivered and three have aborted. No ectopic pregnancies were observed.

PMID- 8150909
TI  - Loa loa microfilariae aspirated during oocyte retrieval.
AB  - Loa loa is a filarial parasite which is mainly confined to West and Central
      Africa. Although considered as mildly pathogenic for people living in endemic
      areas, its appearance in other places might be a cause for concern. We report
      here the unusual finding of Loa loa microfilariae in the follicular aspirate of a
      35-year-old black women during oocyte retrieval for in-vitro fertilization. Most
      likely these microfilariae were aspirated, along with follicular fluid, from the
      small blood vessels around the ovarian follicles, which are frequently lacerated
      during ovarian puncture. Despite the spectacular microscopic view of vigorous
      moving worms trapped on the cumulus cells, the presence of Loa loa microfilariae
      does not seem to prevent fertilization and cleavage completely.

PMID- 8150910
TI  - Influence of spermatozoa characteristics on gamete intra-fallopian transfer
      procedures: analysis of results obtained utilizing normozoospermic,
      oligoasthenozoospermic and donor spermatozoa.
AB  - The objective of this study was to analyze the efficacy of the gamete intra
      Fallopian transfer (GIFT) procedure in relation to spermatozoa characteristics. A
      total of 268 infertile couples enlisted for GIFT were categorized into three
      groups on the basis of semen characteristics in the husband. These included
      oligoasthenozoospermic men in 88 retrieval cycles (group 1), normozoospermic men
      in 116 cycles (group 2) and azoospermic partners who needed donor semen in 86
      cycles (group 3). All female patients had ovarian stimulation and laparoscopic
      GIFT. Pregnancy rates were significantly higher with donor spermatozoa than with
      oligoasthenozoospermic or normozoospermic spermatozoa, i.e. 51.1% versus 15.9% (P
      < 0.001), and 32.7% (P < 0.005). Implantation rates were significantly higher
      with donor spermatozoa than with normo- or oligoasthenozoospermic spermatozoa (P
      < 0.01). These data suggest that GIFT does not give good results with male factor
      infertility. Donor cryopreserved semen gives higher pregnancy and implantation
      rates than normozoospermic semen, and GIFT with donor spermatozoa gives a good
      chance of pregnancy to couples previously treated with artificial insemination
      using donor semen.

PMID- 8150911
TI  - Pentoxifylline-enhanced acrosome reaction correlates with fertilization in vitro.
AB  - To evaluate the possible effect of pentoxifylline on the acrosome reaction (AR)
      and its correlation with in-vitro fertilization (IVF), sperm samples obtained
      from 51 patients who underwent IVF treatment were studied. Acrosome reactions
      were evaluated as spontaneous, pentoxifylline-treated and calcium ionophore
      (A23187) induced, before and after treatment. The correlation of AR with
      fertilization in vitro in spermatozoa pre-treated with pentoxifylline was sought.
      In cases with failure or very low fertilization rate (< or = 10%) in their
      previous trials, spermatozoa after swim-up were treated before insemination.
      Spontaneous acrosome loss remained low even after treatment (mean +/- SD: 8.18 +/
      1.74%). Response to A23187 was enhanced significantly (P < 0.001) by pre
      treatment with pentoxifylline in 33 control cases (group A) in which
      fertilization in vitro was previously successful without this treatment. Patients
      with at least two episodes of failed fertilization were divided into two groups.
      In 11 cases (group B), the IVF rate was improved significantly (P < 0.001) by the
      treatment. This was not observed in seven cases (group C) in which the treatment
      induced no increase in IVF rate. We achieved nine (27.3%) pregnancies in group A
      and five (45.4%) pregnancies in group B. This study demonstrated that
      pentoxifylline enhanced A23187 induced the acrosome reaction and this effect was
      correlated with improvement in IVF rate.

PMID- 8150912
TI  - Fibrin glue for anastomosis of the fallopian tube--morphology.
AB  - In a morphological study fibrin-glued tubal anastomoses were compared with
      classical anastomoses using microsutures. In the isthmic-isthmic anastomoses,
      whether they were glued or sutured, the opposition of the folds and the
      continuity of the tubal wall were good. Scanning electron microscope studies of
      Fallopian tubes subjected to anastomosis using fibrin glue or microsurgical
      sutures showed a break in the fold structure regardless of the technique used,
      with formation of polyp-like and tuborous structures in some of the anastomoses
      in the ampullary region. In one case of an ampullar-ampullar anastomosis with
      fibrin glue, formation of a fistula was observed and in another case of the same
      type of anastomosis a hydrosalpinx developed as the consequence of intratubal
      adhesions and stenosis. In glued anastomoses in particular, intraluminal fibrin
      deposits were observed. Otherwise our scanning and transmission electron
      microscope investigations of the region of the anastomoses revealed a normal cell
      picture with abundant cilia-bearing, structurally unremarkable cells. Fibrin
      glueing can thus be regarded as a possible alternative to the conventional
      microsurgical suturing technique for the construction of anastomoses in the
      isthmic segment of the tube. In the case of wide-lumen ampullary anastomoses,
      however, the danger of fistula formation, dehiscence, development of intraluminal
      adhesions and stenosis must be regarded as increased. Fibrin glueing also does
      not appear to be appropriate for anastomoses requiring approximation of differing
      luminal widths.

PMID- 8150913
TI  - Mitochondrial distribution after fast embryo freezing.
AB  - Mitochondrial distribution pattern after ultrarapid freezing in
      dimethylsulphoxide was assessed in human multipronucleate zygotes, 2-cell and 4
      cell stage embryos using rhodamine 123. The mitochondrial distribution pattern
      was evaluated at 37 degrees C after a 30 min incubation in rhodamine 123
      solution, 4 h and 24 h after thawing. Non-frozen human unfertilized oocytes, 2
      cell and 4-cell embryos used as a control showed a homogeneous distribution of
      mitochondria throughout the cytoplasm, while there was sequestration of
      mitochondria from the cortex to the region surrounding the pronuclei in
      multipronucleate zygotes. Morphologically intact multipronucleate zygotes, 2-cell
      and 4-cell stage embryos after quick freeze-thawing showed the same mitochondrial
      distribution pattern found in the unfrozen controls. Mitochondria exhibited a
      typical severe aggregation (clumping) throughout the cytoplasm when non-viable
      single blastomeres or embryos at thawing were exposed to rhodamine 123. Our study
      indicates that quick freezing does not affect subcellular structures. The well
      organized and specific mitochondrial distribution appeared still to be present
      after frozen storage, and subcellular structures seemed to be rather resistant
      targets for cryo-injury.

PMID- 8150914
TI  - Human blastocyst grading: an indicator of developmental potential?
AB  - We have observed marked variation in the in-vitro development of individual human
      embryos to the blastocyst stage which was poorly associated with the grade of the
      embryo on the day of transfer (day 2). Therefore we also graded embryos at the
      blastocyst stage to determine if their development potential can be better
      predicted at this stage. A total of 41 blastocysts were categorized into three
      grades depending on their morphology. Various parameters such as hatching,
      adherence, growth and amount of human chorionic gonadotrophin (HCG) secreted were
      documented. The number of nuclei in another 34 blastocysts belonging to the three
      grades were measured. Also morula stage embryos with large vacuoles but no
      morphological differentiation were included in a separate group called
      'vacuolated morulae'. Overall, there was no significant difference between grade
      1 and 2 blastocysts as assessed by their development to day 14, cumulative HCG
      secretion and nuclei counts. Grade 3 blastocysts reflected 'poor' morphology,
      secreted significantly lower levels of HCG and had significantly fewer nuclei
      than the other two grades. Vacuolated morulae did not resemble blastocysts in
      their morphological development, secreted no HCG and had significantly fewer
      nuclei than grade 1 and 2 blastocysts. This study illustrates the need for
      selecting blastocysts for transfer to the uterus or for cryopreservation to allow
      a better assessment of the success of these techniques. In addition, the data
      will be useful for evaluating the effects of techniques such as co-culture with
      feeder cells on the development of embryos to the blastocyst stage and beyond.

PMID- 8150915
TI  - Determination of the acrosome reaction in human spermatozoa is predictive of
      fertilization in vitro.
AB  - The acrosome reaction was determined in aliquots from ejaculates of 74 patients
      undergoing in-vitro fertilization at the University of Giessen, Germany, by means
      of the triple-stain technique. The percentage of acrosome-reacted spermatozoa
      after low-temperature induction of the acrosome reaction was not significantly
      related with the fertilization rate (H test, P = 0.693, SJ test, P = 0.366).
      However, all patients showing < 13.0% acrosome-reacted spermatozoa had poor
      fertilization rates. Highly significant differences between patients could be
      detected by correlating the inducibility of the acrosome reaction with the
      fertilization rate (H test, P = 0.018; SJ test, P = 0.004); patients with high
      fertilization rates showed a corresponding high inducibility of acrosome
      reactions. From our results, it is evident that percentages of acrosome-reacted
      spermatozoa < 13.0% or an inducibility of the acrosome reaction of < 7.5% are
      indicative of subfertility.

PMID- 8150916
TI  - Granulosa cells improve human embryo development in vitro.
AB  - A total of 17 couples with repetitive implantation failure after transfer of
      fresh or frozen-thawed embryos had half of their zygotes cultured in standard
      conditions and frozen at day 2 after insemination, and the other half cocultured
      with autologous granulosa cells and transferred at the morula or blastocyst stage
      at day 5 or 6 after oocyte retrieval. At the end of the culture period,
      supernatants of cocultures were recovered for steroid assays. Monolayers were
      stained for granulosa cell growth and morphological assessment. We observed that
      granulosa cells improve embryo development in vitro since 32 out of 60 (53%)
      reached the morula stage and 18 (30%) the blastocyst stage, leading to a total of
      83% embryos available for transfer (compared with 3% without coculture). The
      ongoing pregnancy rate of these patients who were selected because they had at
      least three previous implantation failures, is only 5.9%, however, which is
      similar to the control group without coculture (6.3%). To conclude, granulosa
      cells improve embryo development but not the pregnancy rate after transfer of
      cocultured embryos in patients with multiple previous implantation failures.

PMID- 8150917
TI  - Head-specific mannose-ligand receptor expression in human spermatozoa is
      dependent on capacitation-associated membrane cholesterol loss.
AB  - D-Mannose binding lectins appear on the human sperm head following in-vitro
      incubation under capacitating conditions. Surface expression of lectin is
      dependent on reduction of the sterol content of sperm membranes. Mannose-specific
      lectin distribution over the head differs in acrosome-intact and acrosome-reacted
      spermatozoa. Sugar competition experiments show that mannose is the only
      saccharide competitive with D-mannosylated albumin binding and that free mannose
      induces an acrosome reaction in capacitated spermatozoa. A total of 183 men with
      normozoospermic semen parameters were screened for the ability of their
      spermatozoa to bind fluorescein isothiocyanate (FITC)-labelled mannosylated
      albumins, before and after incubation in vitro. The spermatozoa from 176 men
      'responded' to incubation by exhibiting time-dependent increases in head-directed
      mannosylated albumin binding, accompanied by increases in the percentage of
      spermatozoa showing spontaneous acrosome loss. Motile spermatozoa from the
      remaining seven men failed to express mannose-lectin binding activity after 18 h
      of incubation and only low percentages of their spermatozoa showed spontaneous
      acrosome loss. These seven men were classified as 'non-responders'. The relative
      amounts of non-esterified cholesterol in the sperm membranes of the responder and
      non-responder males were analysed by gas-liquid chromatography. Responder
      spermatozoa showed decreases in free cholesterol content whereas non-responder
      spermatozoa exhibited either no decrease or increases in relative free
      cholesterol per cell. Fresh swim-up spermatozoa contain sub-plasma membrane
      stores of mannose lectins which are revealed by FITC-mannosylated albumin
      labelling before and after removal of the plasma membrane by vortexing. In
      contrast, the mannose-lectin binding activity of capacitated spermatozoa is
      entirely limited to the sperm surface. Western blots of proteins isolated from
      sperm plasma membranes after capacitation revealed two molecular species reactive
      with polyclonal antibodies against human macrophage mannose receptors. A model is
      proposed for the molecular mechanism whereby mannose lectins are transposed from
      sub-plasma membrane sites to an integral membrane position as a consequence of
      the loss of cholesterol from the sperm membrane.

PMID- 8150918
TI  - Fertilization potential in vitro is correlated with head-specific mannose-ligand
      receptor expression, acrosome status and membrane cholesterol content.
AB  - Normozoospermic men who do not fertilize human eggs in vitro constitute a clearly
      identifiable class of occult male factor infertility. We have studied the
      relationships between in-vitro fertilization (IVF) outcomes and the appearance of
      sperm surface mannose lectin/zona pellucida ligand activity measured by the
      binding of fluorescein isothiocyanate (FITC)-labelled mannosylated albumin. Of
      338 semen specimens with normal profiles, 10 (2.96%) failed to fertilize in vitro
      (IVF-). Motile spermatozoa from six of these were analysed retrospectively for
      zona ligand binding activity on the sperm head in relation to acrosome status and
      the free cholesterol content of their plasma membrane. IVF+ males and fertile
      donors served as controls. The six IVF- occult male factor cases were
      distinguished from controls by their failure to show time-dependent increases in
      the percentage of spermatozoa exhibiting head-directed mannose ligand activity,
      by the slow loss or apparent increase in membrane cholesterol and by the absence
      of spontaneous and/or mannose-induced acrosome exocytosis.

PMID- 8150919
TI  - Evidence of sperm entry into assumed unfertilized human oocytes after sub-zonal
      sperm microinjection.
AB  - Sub-zonal sperm microinjection (SUZI) as a treatment for male factor infertility
      can facilitate fertilization, however, in many cases oocytes remain unfertilized
      even though the sperm is placed in close contact with the oolemma. In order to
      improve our understanding of gamete interaction in cases of failed fertilization,
      we have analysed the failed fertilized oocytes from both SUZI and conventional in
      vitro fertilization. The fluorochrome Hoechst 33342 (which binds specifically to
      DNA) was used to check for the possible presence of paternal chromatin in the
      unfertilized oocytes. A significantly higher (P < 0.01) number of microinjected
      oocytes showed signs of fertilization 2-3 days after sperm microinjection
      compared to normally inseminated oocytes, 30/175 (17.1%) and 2/79 (2.5%)
      respectively. In addition, four out of eight couples returning for a second
      treatment by SUZI displayed anomalies in fertilization in both cycles. The semen
      characteristics of patients with or without anomalies in fertilization was not
      different. The irregularities observed in the fertilization process infer that
      certain male factor patients have intrinsic sperm anomalies lying at the sperm
      membrane and/or chromatin level that could lead to anomalies in the appearance of
      the pronuclei.

PMID- 8150920
TI  - Oscillations in intracellular free calcium induced by spermatozoa in human
      oocytes at fertilization.
AB  - Calcium has an important role in the events of egg activation and early
      preimplantation development. We investigated changes in intracellular calcium
      concentration in human oocytes at fertilization using the calcium-sensitive
      photoprotein aequorin. Oocytes were donated for research by patients undergoing
      in-vitro fertilization treatment in the Department of Obstetrics and Gynaecology.
      Cumulus cells, and in some cases zonae pellucidae, were removed by appropriate
      enzyme treatment. Single oocytes were micro-injected with aequorin and incubated
      in a chamber perfused with pre-equilibrated culture medium in a photomultiplier
      system. Eleven zona-intact and 15 zona-free oocytes were incubated with sperm,
      and oocytes from each group were incubated without sperm as controls. Dramatic
      transient increases in intracellular free calcium concentration were recorded in
      three zona-intact and seven zona-free oocytes, thought to be the first direct
      measurements of intracellular changes in human oocytes at fertilization. The
      amplitude (up to 2.5 microM), duration (120 s) and frequency (every 10-35 min) of
      these transients were similar in zona-intact and zona-free oocytes. They resemble
      those recorded in mouse oocytes, which may therefore be a suitable model for
      biochemical events at human fertilization.

PMID- 8150921
TI  - Intracytoplasmic single sperm injection of 1-day-old unfertilized human oocytes.
AB  - Although the average fertilization rate in most in-vitro fertilization (IVF)
      centres is approximately 60-70%, there are cases of complete or virtually
      complete fertilization failures. The aim of our work was to study the
      fertilization and the subsequent cleavage characteristics of 1-day-old human
      oocytes treated by intracytoplasmic single sperm injection (ICSI) after failing
      to fertilize during the standard IVF procedure. A total of 115 metaphase II 1-day
      old unfertilized oocytes were collected from 23 patients. No additional treatment
      was applied to the oocytes or to the semen sample. A single spermatozoon from the
      patient's husband was injected into the cytoplasm of each of these oocytes 21-33
      h after ovum retrieval. Injected oocytes were observed at 16-18 h and again 42-44
      h after the ICSI procedure. Of the injected oocytes, 92% (n = 106) were intact
      after ICSI, 38% (n = 44) had two distinct pronuclei and there was no difference
      in the fertilization rate of oocytes when andrological and non-andrological
      patients were compared. Similarly, there was no difference in the fertilization
      rate after ICSI where patients with acceptable or good (> 15%) fertilization
      after standard IVF were compared to patients who had poor (< or = 15%)
      fertilization after IVF. There was no significant difference in the sperm
      concentration or in the progressive forward motility (a + b motility) in these
      groups except where a + b motility of andrological and non-andrological patients
      was compared. The majority (84%) of the normally fertilized oocytes cleaved and
      most (77%) of these embryos showed < 20% fragmentation 2 days after the ICSI
      procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150922
TI  - Diagnosis of major chromosome aneuploidies in human preimplantation embryos.
AB  - A short fluorescence in-situ hybridization (FISH) procedure using fluorochrome
      and digoxigenin labelled DNA probes was developed for application in human
      preimplantation embryos in order to analyse the five chromosomes most involved in
      human aneuploidy (X, Y, 18, 13 and 21). The chromosomes were fluorescent-stained
      and detected simultaneously in 157 blastomeres from 30 human embryos. Successful
      FISH analysis was achieved in 93% of the blastomeres. Aberrations for these
      chromosomes were found in 70% of abnormally developing monospermic embryos. The
      majority of normally developing monospermic embryos obtained from older patients
      were also chromosomally abnormal. By analysing all or most of the cells from
      these embryos, true mosaicism was distinguished from technique failure. Mosaic
      embryos, polyploid embryos with ploidies as high as 8n, haploid embryos, embryos
      monosomic for 13/21 and for X, and embryos trisomic for 13/21 and 18, were common
      in abnormally developing embryos. In contrast, aneuploidy was the main chromosome
      abnormality found in normally developing monospermic embryos.

PMID- 8150923
TI  - Preimplantation diagnosis or chorionic villus biopsy? Women's attitudes and
      preferences.
AB  - The objective of this work was to assess women's attitudes and preferences to two
      methods of prenatal diagnosis for genetic disease: embryo and chorionic villus
      biopsy (CVS). The design involved a structured postal questionnaire sent to women
      in the Grampian region with different reproductive experiences. The population
      sample included 46 women who had had genetic counselling because of a family
      history of a single gene disorder, 18 women who had had CVS for a single gene
      disorder, 158 women who had had CVS for other reasons, 200 women who had recently
      delivered a normal baby and 50 women who had experience of in-vitro fertilization
      (IVF). The main outcome measures were attitudes to family limitation, prenatal
      diagnosis, termination for fetal abnormality, embryo biopsy and CVS. Of the women
      surveyed, 38% preferred embryo diagnosis, whereas 42% favoured CVS and
      termination. Women with previous experience of CVS preferred this option whereas
      those with experience of IVF as infertility treatment were more likely to favour
      embryo diagnosis, as were women who had had genetic counselling for a single gene
      disorder. It was concluded that a substantial number of women find embryo
      diagnosis more acceptable than CVS when the pregnancy is at high risk. This is
      especially true amongst those with experience of IVF or who are at risk
      themselves. A demand for embryo diagnosis has been demonstrated.

PMID- 8150924
TI  - Biopsy of the human blastocyst and polymerase chain reaction (PCR) amplification
      of the beta-globin gene and a dinucleotide repeat motif from 2-6 trophectoderm
      cells.
AB  - Cultured human blastocysts have been biopsied on day 5-6 post insemination and 2
      6 extra-embryonic cells from the trophectoderm were removed and their DNA
      subjected to specific amplification by the polymerase chain reaction (PCR).
      Simultaneous amplification of part of the beta-globin gene and a dinucleotide
      repeat sequence has been achieved in a high percentage of cases when using the
      DNA from both trophectoderm cell biopsies and biopsied blastocysts as template
      for the PCR. A similar success rate was achieved when serial biopsies were taken
      from the same blastocyst, thus allowing one cell sample to be held in reserve for
      use should equivocal results be obtained. Over the entire experimental period (5
      months), no contamination was experienced with biopsy or PCR procedures.
      Following biopsy of the trophectoderm cells all blastocysts had reformed a
      blastocoele cavity within 3-4 h of the biopsy procedure. Those blastocysts
      remaining in culture after this time showed a high incidence (78-83%) of hatching
      and outgrowth.

PMID- 8150925
TI  - Primer extension preamplification for detection of multiple genetic loci from
      single human blastomeres.
AB  - A new technology called primer extension preamplification (PEP), which has been
      applied to single spermatozoa, increases the amount of polymerase chain reaction
      (PCR) templates by amplifying DNA of the whole genome. The current investigation
      was aimed at applying PEP to single human blastomeres. Two blastomeres with
      nuclei from arrested embryos were selected for this study. Using three different
      PEP protocols (experiments I, II and III), DNA from single blastomeres was
      amplified using 15-base oligonucleotide random primers. The efficiency of the
      procedure was determined by further amplifications of aliquots of the PEP
      products with two specific sequences. Three aliquots from each PEP product were
      used as PCR templates for the human X chromosome (X) or the exon 10 of the cystic
      fibrosis gene (CF). PCR amplified products were analysed by gel electrophoresis.
      In experiment I, when X primers were used, positive signals were detected in all
      10 embryos (100%), 90.0% (18/20) of the blastomeres, and in 80.0% (96/120) of the
      replicates. When CF primers were amplified, all embryos (100%, 10/10), 90.9%
      (18/20) of the blastomeres and 78.3% (47/60) of the replicates were positive. In
      experiment II, efficiency was significantly reduced when total time for the
      procedure was minimized from 8 h to 5 h and 45 min. Although the time was further
      reduced to 4 h and 40 min in experiment III, the efficiency remained the same as
      in experiment I when the volume of PEP was reduced from 60 microliters
      (experiments I and II) to 40 microliters. One out of 132 control replicates
      (0.8%) was contaminated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8150926
TI  - Oestrogen and progesterone receptors in endometriotic tissue and endometrium:
      comparison of different cycle phases and ages.
AB  - The levels of oestrogen and progesterone receptors were analysed in 62
      endometriotic tissue samples obtained at laparotomy of 58 women and in samples of
      endometrium obtained simultaneously from 49 of the women. Both ligand techniques
      and enzyme immunoassays were used for the assays. The steroid receptor levels
      were significantly lower in endometriotic tissue than in endometrium, both in
      cytosol and nuclear fractions. The differences were most pronounced in follicular
      phase. In endometrium the oestrogen and progesterone receptor levels varied
      during the menstrual cycle, being highest in follicular phase. In endometriotic
      tissue, the oestrogen receptor level remained low throughout the cycle. The
      progesterone receptor level, determined by immunoassay, increased during the
      menstrual cycle, being higher in luteal than in follicular phase. This cycle
      phase pattern was found neither in the nuclear progesterone receptor level nor
      when the cytosol was assayed with the ligand technique. In contrast to
      endometrium, there were no correlations between patients' age and steroid
      receptor levels in endometriotic tissue. The results show that oestrogen and
      progesterone receptors in endometriotic tissue have a different pattern during
      the menstrual cycle than endometrium and that the progesterone receptors
      synthesized are not all biologically active. These results strengthen previous
      data indicating differences in the hormonal regulation of the two tissue types.

PMID- 8150927
TI  - Scanning electron microscopic and immunohistochemical studies of pelvic
      endometriosis.
AB  - The pathogenesis of pelvic endometriosis has been studied by using scanning
      electron and light microscopy, observing the surface structure of bluish lesions
      obtained from 26 patients during laparotomy. Paraffin sections included another
      17 tissue samples of endometriosis, based on immunohistochemical responses to
      epithelial membrane antigen, keratin and vimentin. Ultrastructurally, the surface
      epithelial cells could not be detected in 13 out of 17 pelvic peritoneal
      endometriosis samples. In one case in which the surface peritoneal cells were
      seen histologically to dip into the subperitoneal stroma, many surface peritoneal
      infoldings were observed, and ciliated cells were detected at the edge of these
      infoldings. Ovarian endometriosis was composed of three types of cells, none of
      which had any cilia. These findings were observed in continuity with adjacent
      normal mesothelial cells. No characteristic structure of the endometrial surface
      was observed for the bluish lesion, but the gland surface of endometriosis
      located in the subperitoneal stroma initially had ciliated cells. The
      immunoreactions in both the columnar mesothelial cells with surface peritoneal
      infoldings and the glands of endometriotic tissues were similar to those of
      normal endometrial glands, but different from those of normal mesothelial cells.
      Pelvic endometriosis might originate by a process of metaplasia from the pelvic
      peritoneum.

PMID- 8150928
TI  - Operative laparoscopy for ectopic pregnancy: how experienced should the surgeon
      be?
AB  - The purpose of this study was to assess the efficacy of laparoscopic surgery for
      ectopic pregnancy in a general hospital in Paris, where most of the surgeons are
      still in training. During a period of 20 months, 100 cases of ectopic pregnancy
      were diagnosed and treated by the attending residents. Nine cases required a
      laparotomy due to heavy bleeding or interstitial ectopic pregnancy. Most of the
      other cases were treated laparoscopically, with either salpingectomy (70 cases)
      or linear salpingostomy (19 cases). Complications of the laparoscopic surgical
      procedures were rare. There was one failure of linear salpingostomy that required
      a second intervention (5.3% failure rate); there was one case of urinary
      retention that resolved after 48 h; and one case of fever above 38 degrees C that
      responded well to antimicrobial therapy. In conclusion, we have shown that the
      current notion that laparoscopic surgery is preferred to conventional abdominal
      surgery for the treatment of ectopic pregnancy, can be applied to a public
      gynaecological centre with young inexperienced residents, supervised by
      experienced gynaecologists.

PMID- 8150929
TI  - Combined intra-uterine and extra-uterine pregnancy in the contralateral tube
      after gamete intra-fallopian transfer.
AB  - A case of combined intra-uterine and contralateral tubal pregnancy after gamete
      intra-Fallopian transfer (GIFT) is presented. Laparotomy with partial tubal
      resection was performed after tubal rupture. The intra-uterine pregnancy is still
      ongoing without complications. Heterotopic pregnancies are dangerous conditions
      for the patient and should be taken into account after transfer of multiple
      oocytes. To our knowledge this is the first report of a heterotopic pregnancy in
      the contralateral tube after GIFT.

PMID- 8150930
TI  - Low-dose aspirin for prevention of pregnancy losses in women with primary
      antiphospholipid syndrome.
AB  - Pregnancy loss, often recurrent, is one of the most important clinical
      manifestations associated with the primary antiphospholipid syndrome. In these
      cases, pregnancy wastage is related to the presence of antiphospholipid
      antibodies, namely lupus anticoagulant and anticardiolipin antibodies, but
      patients do not have features of systemic lupus erythematosus or any other well
      defined autoimmune disease. We report here on the outcome of 21 consecutive
      pregnancies in 18 patients with the syndrome who were treated with low-dose
      aspirin (100 mg/day) from 1 month before attempting conception and throughout the
      pregnancy. Low-dose prednisone (15-30 mg/day) was added for potentially non
      obstetric (autoimmune-related) reasons in six pregnancies. Patients were
      monitored as having high-risk pregnancies. Prior to therapy, the rate of live
      born babies was 6.1% (46 previous fetal losses and three live-born babies), and
      after therapy, it was 90.5% (21 pregnancies and 19 live-born babies). Pre-term
      delivery due to maternal or fetal indications was required in 15% (3/20) of the
      viable pregnancies. Except for prematurity (20% of viable pregnancies) and its
      potential associated complications, there were no significant adverse effects to
      either mothers or babies. Our treatment modality is advocated for prevention of
      pregnancy losses in patients with the 'obstetric' primary antiphospholipid
      syndrome.

PMID- 8150931
TI  - Dizygotic triplet pregnancy following in-vitro fertilization.
AB  - We present a case of dizygotic triplet pregnancy (mono-amniotic twins and a
      singleton) that, as far as we know, is the first reported one induced by
      artificial reproductive technology. It ended in the delivery of three healthy
      normal babies: two monozygotic twin boys and a girl. It appears that zygote
      splitting is significantly more common in patients treated with ovulation
      inducing agents than in the general population. Also, in-vitro conditions of
      embryonic growth might influence the chances of multifetal gestation and the
      incidence of identical twinning. This may be due to changes in the physical
      properties of the zona pellucida and subsequent partial hatching of the pre
      embryo. Evaluation of similar cases in the future may shed more light on the
      mechanism underlying their occurrence following in-vitro fertilization.

PMID- 8150932
TI  - Quadruplet pregnancy in a 51-year-old menopausal woman following oocyte donation.
AB  - A quadruplet pregnancy occurred in a woman 51 years of age following oocyte
      donation and embryo transfer. Successful pregnancy occurred following two
      previously unsuccessful attempts. The patient underwent a selective reduction of
      her pregnancy to two fetuses at approximately 13 weeks gestational age. Her
      pregnancy continued uneventfully and she underwent the delivery of two viable
      infants at 38 weeks gestational age by Caesarean section. This case represents
      the first quadruplet pregnancy to be established in a woman of 50 years of age or
      older. It illustrates both the benefits and risks of oocyte donation to women of
      advanced reproductive age.

PMID- 8150933
TI  - Ovulation induction agents and ovarian cancer.

PMID- 8150934
TI  - The ecological context of human ovarian function.
AB  - New methods for monitoring ovarian function have allowed an extension of research
      venue beyond typical clinical settings to studies of human populations in their
      natural settings. Such studies have confirmed that patterns of variation in
      ovarian function with age and energetic factors are general features of human
      reproductive biology. Age patterns of ovarian function are extremely robust
      across populations of distinct genetic, ecological and cultural backgrounds.
      Comparable ovarian responses to energetic stresses are likewise observable in
      different populations where they arise as correlates of local ecologies rather
      than as correlates of voluntary patterns of diet or exercise. Maternal age and
      energetic factors also appear to interact with lactation in the modulation of
      postpartum, ovarian function. Average levels of ovarian function, however, differ
      considerably between populations, perhaps correlated with chronic environmental
      conditions that affect growth, development, and the establishment of adult set
      points. Western populations appear to represent an extreme of the spectrum of
      variation in ovarian function, a fact which may relate to the epidemiology of
      breast and ovarian cancer.

PMID- 8150936
TI  - Nested PCR for specific detection and rapid identification of human
      picornaviruses.
AB  - A nested PCR for the detection and rapid identification of human picornaviruses
      is described. Enteroviruses and rhinoviruses were amplified with the same set of
      four primers from the 5'-noncoding region. The nested primers allowed the
      detection of far less than 1 PFU in diluted virus stocks without Southern blot
      hybridization. In patients with neurological disorders (mainly aseptic
      meningitis), 43% of 37 specimens (11 of 21 cerebrospinal fluid specimens, 2 of 10
      serum specimens, and 3 of 6 stool specimens) were positive by PCR. A total of 21%
      (10 of 47 specimens) of heart biopsy specimens from patients with dilative
      cardiomyopathy were PCR positive, whereas 3% (2 of 70 specimens) of control
      biopsy specimens from patients with coronary artery disease were PCR positive.
      PCR-amplified fragments from 27 of 29 clinical isolates and 14 of 28 patient
      samples were successfully serotyped by restriction enzyme digestion. Two
      specimens were further investigated by direct sequencing of PCR products, leading
      to the identification of a poliovirus type 3 isolate with a sequence that was
      highly divergent from previously published sequences.

PMID- 8150935
TI  - Sensitivity and specificity of PCR for detection of Mycobacterium tuberculosis: a
      blind comparison study among seven laboratories.
AB  - PCR is, in principle, a simple and rapid test for use in the detection of
      Mycobacterium tuberculosis. However, virtually no data are available on the
      reliability and reproducibility of the method. In order to assess the validity of
      PCR for the detection of mycobacteria in clinical samples, seven laboratories
      participated in a blinded study of 200 sputum, saliva, and water samples
      containing either known numbers of Mycobacterium bovis BCG cells or no added
      organisms. Each laboratory used its own protocol for pretreatment, DNA
      extraction, and detection of the amplification product. Insertion sequence IS6110
      was the target for DNA amplification. Several participating laboratories reported
      high levels of false-positive PCR results, with rates ranging from 3 to 20% and
      with one extreme value of 77%. The levels of sensitivity also ranged widely among
      the different participants. A positive PCR result was reported for 2 to 90% of
      the samples with 10(3) mycobacteria. Although most participants did include
      control tests to check the sensitivity and specificity of the PCR, the sequence
      of operations from sample pretreatment to purification of DNA from bacteria was
      not always monitored adequately. During these procedures cross-contaminating DNA
      was introduced and/or bacterial DNA was lost. The results of the study show that
      the implementation of an effective system for monitoring sensitivity and
      specificity is required before the PCR can be used reliably in the diagnosis of
      tuberculosis.

PMID- 8150937
TI  - Rapid and simple PCR assay for quantitation of human immunodeficiency virus type
      1 RNA in plasma: application to acute retroviral infection.
AB  - A method for quantitating human immunodeficiency virus type 1 plasma viremia may
      be useful in monitoring disease progression and the responsiveness of patients to
      a therapeutic regimen or vaccine. A quantitative assay for viral RNA in plasma or
      sera that differs in several aspects from those reported previously was
      developed. First, whereas conventional reverse transcriptase-PCR assays involve a
      two-step process and use two enzymes, the method described uses a single enzyme,
      rTth DNA polymerase, for both reverse transcription and PCR. The reactions are
      carried out in a single tube and with a single buffer solution with uninterrupted
      thermal cycling. Second, uracil-N-glycosylase and dUTP are incorporated into the
      reaction mixtures to ensure that any carryover of DNA from previous
      amplifications will not compromise quantitation. Third, a quantitation standard
      is incorporated into each reaction mixture so that differences in amplification
      efficiency caused by sample interferents, variability in reaction conditions, or
      thermal cycling can be normalized. To ensure comparable amplification efficiency,
      the quantitation standard has the same primer-binding regions as the human
      immunodeficiency virus type 1 target and generates an amplified product of the
      same size and base composition. The probe-binding region was replaced with a
      sequence that can be detected separately. Fourth, a colorimetric detection format
      was modified to provide at least a four-log-unit dynamic range. The quantitative
      assay requires only a single amplification of the sample and can be completed in
      less than 8 h. The procedure was used on archival samples to demonstrate the
      viremic spike in acute infection and the suppressed levels of circulating virus
      following seroconversion.

PMID- 8150938
TI  - Epidemiological study by pulsed-field gel electrophoresis of an outbreak of
      extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a geriatric
      hospital.
AB  - Twelve cases of infections caused by extended-spectrum beta-lactamase (ESBla)
      producing Klebsiella pneumoniae were reported between August 1991 and March 1993
      in the Geriatric Department of the Nimes University Hospital, where these
      bacterial had not been previously isolated. Restriction profiles of total genomic
      DNAs cleaved by XbaI and SpeI were compared by pulsed-field gel electrophoresis.
      The strains that were tested included the 12 isolates from K. pneumoniae-infected
      patients, strains recovered from rectal swabs of asymptomatic patients in the
      same ward, and strains isolated in other hospitals in Nimes at the same time. The
      restriction profiles of the 12 isolates and those recovered from asymptomatic
      patients in the same ward were very similar. Over a period of more than 1 year,
      extended-spectrum beta-lactamases were not detected in K. pneumoniae isolates
      with restriction patterns different from that of the epidemic strain. It seems,
      therefore, that there was no transfer of a plasmid or a gene coding for ESBla to
      strains of K. pneumoniae that were different from the epidemic strain. At the
      same time, ESBla-producing K. pneumoniae isolates exhibiting restriction
      endonuclease profiles very different from that of the epidemic strain were
      isolated from other hospitals in Nimes. None of these strains caused an outbreak.
      Pulsed-field gel electrophoresis, which allows precise characterization of
      strains beyond the species level, is a useful tool for studying the ESBla
      producing K. pneumoniae strains involved in nosocomial outbreaks.

PMID- 8150939
TI  - Sequence analysis of the 5' untranslated region in isolates of at least four
      genotypes of hepatitis C virus in The Netherlands.
AB  - The RNAs of hepatitis C virus (HCV) isolates from 62 patients with chronic HCV
      infection were analyzed by direct sequencing of the 5' untranslated region. Two
      important sequence motifs were recognized: one between positions -170 and -155
      and the other between positions -132 and -117. These motifs are partly
      complementary. All three previously published genotypes were observed; 34 (55%)
      isolates were classified as type 1 (including prototype [from the United States]
      and HCV-BK [from Japan] sequences), 11 (18%) were classified as type 2 (including
      HC-J6 and HC-J8), and 12 (19%) were classified as type 3 (including EB1); one
      patient was infected with genotypes 1 and 2. Four (6%) isolates showed aberrant
      sequences and were therefore provisionally classified as genotype 4. These
      results indicate the significance of sequence variation among the 5' untranslated
      regions of different HCV genotypes and indicate that this region could possibly
      be used for consistent genotyping of HCV isolates.

PMID- 8150940
TI  - Serotypic differentiation of rotaviruses in field samples from diarrheic pigs by
      using nucleic acid probes specific for porcine VP4 and human and porcine VP7
      genes.
AB  - Of 216 fecal and intestinal samples collected from nursing or weaned diarrheic
      pigs in the United States and Canada, 57 were identified as group A rotavirus
      positive by RNA electrophoresis and silver staining. Fifty-seven and 52 rotavirus
      positive samples were analyzed by hybridization with Gottfried and OSU PCR
      derived gene 9 and 4 probes, respectively. Only 17 samples were identified with
      either homologous VP4 (P)- or VP7 (G)-coding genes or both. One rotavirus
      identified as G4 and P7 was similar to the previously characterized interserotype
      rotavirus, SB-1A. Additional hybridization analyses were performed with PCR
      derived probes prepared from gene 9 cDNA of the human rotaviruses Wa (G1), DS-1
      (G2), and P (G3) and of the porcine rotavirus YM (G11). Eleven of 52 samples
      collected and analyzed from swine in Ohio, California, and Nebraska were
      identified as G11. No samples with G1-, G2-, or G3-type specificities were
      detected among the 25 of 57 rotavirus-positive samples analyzed with human
      rotavirus-derived probes. Further investigations with a PCR-derived gene 4 probe
      prepared from porcine rotavirus YM revealed hybridization specificities similar
      to those of the OSU gene 4 probe.

PMID- 8150941
TI  - Norwalk virus-associated gastroenteritis traced to ice consumption aboard a
      cruise ship in Hawaii: comparison and application of molecular method-based
      assays.
AB  - Investigation of an outbreak of acute nonbacterial gastroenteritis on a cruise
      ship provided an opportunity to assess new molecular method-based diagnostic
      methods for Norwalk virus (NV) and the antibody response to NV infection. The
      outbreak began within 36 h of embarkation and affected 30% of 672 passengers and
      crew. No single meal, seating, or food item was implicated in the transmission of
      NV, but a passenger's risk of illness was associated with the amount of ice (but
      not water) consumed (chi-square for trend, P = 0.009). Of 19 fecal specimens
      examined, 7 were found to contain 27-nm NV-like particles by electron microscopy
      and 16 were positive by PCR with very sensitive NV-specific primers, but only 5
      were positive by a new highly specific antigen enzyme immunoassay for NV. Ten of
      12 serum specimen pairs demonstrated a fourfold or greater rise in antibody titer
      to recombinant baculovirus-expressed NV antigen. The amplified PCR band shared
      only 81% nucleotide sequence homology with the reference NV strain, which may
      explain the lack of utility of the fecal specimen enzyme immunoassay. This
      report, the first to document the use of these molecular method-based assays for
      investigation of an outbreak, demonstrates the importance of highly sensitive
      viral diagnostics such as PCR and serodiagnosis for the epidemiologic
      investigation of NV gastroenteritis.

PMID- 8150942
TI  - Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population.
AB  - To estimate the extent of meningococcal carriage in the Norwegian population and
      to investigate the relationship of several characteristics of the population to
      the carrier state, 1,500 individuals living in rural and small-town areas near
      Oslo were selected at random from the Norwegian National Population Registry.
      These persons were asked to complete a questionnaire and to volunteer for a
      bacteriological tonsillopharyngeal swab sampling. Sixty-three percent of the
      selected persons participated in the survey. Ninety-one (9.6%) of the volunteers
      harbored Neisseria meningitidis. The isolates were serogrouped, serotyped, tested
      for antibiotic resistance, and analyzed by multilocus enzyme electrophoresis.
      Eight (8.8%) of the 91 isolates represented clones of the two clone complexes
      that have been responsible for most of the systemic meningococal disease in
      Norway in the 1980s. Age between 15 and 24, male sex, and active and passive
      smoking were found to be independently associated with meningococcal carriage in
      logistic regression analyses. Working outside the home and having an occupation
      in transportation or industry also increased the risk for meningococcal carriage
      in individuals older than 17, when corrections for gender and smoking were made.
      Assuming that our sample is representative of the Norwegian population, we
      estimated that about 40,000 individuals in Norway are asymptomatic carriers of
      isolates with epidemic potential. Thus, carriage eradication among close contacts
      of persons with systemic disease is unlikely to have a significant impact on the
      overall epidemiological situation.

PMID- 8150943
TI  - Natural infections with Borrelia spirochetes in two dogs from Florida.
AB  - Spirochetemia is a rarely reported observation in dogs. We describe the clinical,
      hematologic, and immunodiagnostic features of two spirochetemic dogs from
      northern Florida and the subsequent isolation and preliminary characterization of
      a Borrelia species from one dog in which culture of a sample for spirochetes was
      attempted. Results of polyacrylamide gel electrophoresis, monoclonal antibody
      testing, and PCR analysis indicate that the Florida isolate is not Borrelia
      burgdorferi, the only other member of the genus that has been isolated in
      Florida. Our findings also indicate that a member of the genus Borrelia
      potentially causes disease in dogs in Florida and that serologic cross-reactivity
      of the Florida canine Borrelia isolate with B. burgdorferi probably contributes
      to the inaccurate diagnosis of canine Lyme disease in the region.

PMID- 8150944
TI  - Analysis of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum by
      multilocus enzyme electrophoresis.
AB  - The genetic diversity of 74 Australian field isolates of Erysipelothrix
      rhusiopathiae and 22 reference strains for serovars of E. rhusiopathiae or
      Erysipelothrix tonsillarum was examined by multilocus enzyme electrophoresis.
      Four serovar reference strains of E. tonsillarum (strains KS 20 A, Wittling,
      Lengyel-P, and Bano 107 for serovars 25, 3, 10, and 22, respectively) were
      genetically distinct from E. rhusiopathiae. However, the E. tonsillarum reference
      strain for serovar 14 (Iszap-4) and the reference strain for serovar 13 (Pecs
      56), which has been said to represent a new genomic species, were found to
      cluster with typical isolates and reference strains of E. rhusiopathiae. Our
      reference strain for serovar 7 (Rotzunge) was also genetically typical of E.
      rhusiopathiae, thus indicating that these serotype reactivities cannot be relied
      upon as a means of identifying isolates as E. tonsillarum. Australian field
      isolates of E. rhusiopathiae were genetically diverse. Those recovered from sheep
      or birds were more diverse than those isolated from pigs, and isolates of serovar
      1 were more diverse than those of serovar 2. The diversity found among isolates
      of the same serovar and the presence of isolates of different serovars in the
      same electrophoretic types (ETs) indicated that serotyping of E. rhusiopathiae
      was unreliable for use as an epidemiological tool. Some ETs contained isolates
      recovered from different animal species. ET 41 contained 32.2% of the field
      isolates and two reference strains, indicating that this clone of E.
      rhusiopathiae is both widespread and commonly associated with disease in various
      species of animals.

PMID- 8150945
TI  - Correlation between antibiotic resistance, phage-like particle presence, and
      virulence in Rhodococcus equi human isolates.
AB  - Rhodococcus equi is a gram-positive coccobacillus that appears to be emerging as
      a pulmonary pathogen in AIDS patients. In four human clinical isolates, two
      antibiotic resistance phenotypes were found to coexist: one beta-lactam resistant
      and the other beta-lactam susceptible. In vitro, beta-lactam-resistant mutants
      were obtained at a frequency of 1 x 10(-5) to 5 x 10(-5) from beta-lactam
      susceptible strains on cephalothin-containing plates. Neither beta-lactamase nor
      plasmid DNA was detected in beta-lactam-resistant or -susceptible strains. The
      penicillin-binding protein patterns for the two types of strains were identical.
      Electron microscopy revealed that the beta-lactam-resistant strains possessed
      cell-surface-associated appendages and produced phage-like particles. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis of total cell protein showed
      at least three additional bands of 42, 39, and 30 kDa found only in the beta
      lactam-resistant strains. Testing for virulence in Swiss mice revealed that (i)
      phage-like-particle-producing strains had lower 50% lethal doses when injected
      intravenously in euthymic and nude mice than the non-phage-like-particle
      producing strains did and (ii) intravenous inoculation of a sublethal dose (5 x
      10(6) CFU) in nude mice led to chronic infection by the phage-like-particle
      producing bacteria only. Finally, in vitro growth curves indicated that the phage
      like-particle-producing strains possessed an ecological selection advantage.
      These results suggest that, among R. equi human isolates, the antibiotic
      resistance phenotype is associated with virulence and may be phage mediated.

PMID- 8150946
TI  - Characterization, distribution, and microbiological associations of Fusobacterium
      spp. in clinical specimens of animal origin.
AB  - During the years from 1984 through 1991, 1,067 specimens from canine, equine,
      exotic, feline, porcine, and ruminant animal sources were found to contain
      members of the genus Fusobacterium: The most common sites or conditions from
      which members of this genus were isolated were abscesses, the respiratory tract,
      and pleural and peritoneal cavities. Most specimens contained a single
      Fusobacterium species. The most commonly isolated species was Fusobacterium
      necrophorum. Almost all of the specimens contained other obligate anaerobes
      together with facultative and obligate aerobes. The identities of the other
      isolates depended upon the species of animal from which the sample was obtained.

PMID- 8150947
TI  - Clotting activity in Staphylococcus schleiferi subspecies from human patients.
AB  - Staphylococcus schleiferi subsp. schleiferi is a coagulase-negative
      staphylococcus, usually present as a contaminant in human specimens. A near
      relative, S. schleiferi subsp. coagulans, possesses coagulase activity but has
      not been reported from humans. We here describe three isolates of pseudocoagulase
      positive S. schleiferi subsp. schleiferi and one isolate of S. schleiferi subsp.
      coagulans from human patients. The pseudocoagulase from the S. schleiferi subsp.
      schleiferi isolates differs from S. aureus staphylocoagulase by being sensitive
      to a combination of protease inhibitors (aprotinin, N-ethylmaleimide, and
      heparin). These isolates could all easily be confused with S. aureus in a typical
      clinical laboratory, since they all possess a heat-stable DNase and promote
      clotting formation. Moreover, S. schleiferi subsp. coagulans produces protein A,
      and S. schleiferi subsp. schleiferi expresses a clumping factor (fibrinogen
      affinity factor). Southern blot hybridization with an S. aureus coa-specific
      probe revealed no sequence related to the coa gene in any of the S. schleiferi
      isolates, and their riboprobe profiles and biochemical characteristics were
      typical of S. schleiferi subspecies, not of S. aureus. This study demonstrates
      that both subspecies of S. schleiferi can promote clotting of rabbit plasma in
      the standard tube test for coagulase.

PMID- 8150948
TI  - Evaluation of Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test and PCR
      for direct detection of Mycobacterium tuberculosis in clinical specimens.
AB  - The Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTD) is a direct
      specimen assay for the identification of Mycobacterium tuberculosis from
      respiratory samples. rRNA is amplified, and the product is detected with a
      specific chemiluminescent probe. We performed a retrospective evaluation of three
      separate respiratory specimens from each of 250 patients by using the AMTD and
      compared the results with those of microscopy, culturing, and a patient chart
      review. From the latter results, 198 patients (594 specimens) were found negative
      for M. tuberculosis by culturing and clinical criteria. The overall specificity
      of the AMTD after discrepancy resolution was 98.5% (585 of 594). There were 52
      patients with culture-proven and/or clinically diagnosed tuberculosis. Of these
      156 specimens, the organism was cultured from 142 (91%), and acid-fast microscopy
      was positive for 105 (67.3%). The AMTD was positive for 142 (91%) specimens from
      these patients. Tuberculosis patient samples were tested by a PCR assay which
      uses primers for amplification of the IS6110 insertion sequence of the M.
      tuberculosis complex. The PCR assay detected 144 of the 156 (92.3%) specimens.
      Overall, when three specimens per patient were examined, the AMTD found all 52
      patients positive for tuberculosis, while the PCR assay found 51 patients
      positive by agarose gel analysis and all 52 patients positive by Southern blot
      hybridization.

PMID- 8150949
TI  - Use of pulsed-field gel electrophoresis for epidemiological study of Bordetella
      pertussis in a whooping cough outbreak.
AB  - We used pulsed-field gel electrophoresis (PFGE) of chromosomal DNA digested with
      XbaI to determine the distribution of different Bordetella pertussis strains from
      clinical isolates obtained during a large whooping cough outbreak that occurred
      in Alberta, Canada, from December 1989 to May 1991. Our initial study analyzed 28
      clinical isolates, 14 from the city of Edmonton and 1 from each of 14 northern
      Alberta towns. These clinical isolates were randomly chosen over the course of
      the 18-month outbreak. The DNA profiles were more heterogeneous than anticipated
      and caused concern that PFGE was too sensitive a technique to characterize
      strains. Further analysis showed that this was not the case, as clusters of
      similar PFGE patterns were observed in strains isolated from the same outlying
      town. Identical PFGE patterns were also seen in clinical strains obtained from
      different members of the same family. Two PFGE pattern types, a and b,
      predominated in the outbreak, accounting overall for 44 of 70 B. pertussis
      strains tested. Results from isolates from outlying towns, however, indicated
      involvement of local strains rather than a single, highly infectious strain in
      the whooping cough outbreak in Alberta.

PMID- 8150950
TI  - Diagnosis of human immunodeficiency virus (HIV) infection: multicenter evaluation
      of a newly developed anti-HIV 1 and 2 enzyme immunoassay.
AB  - A new anti-human immunodeficiency virus type 1 and 2 (anti-HIV 1 and 2) test is
      described. It uses recombinant p24 and peptides covering gp32, gp41, and gp120 to
      identify HIV-1 and HIV-2 infections. This test has been shown to be specific
      (99.5%) and sensitive (99.8%). In this respect, the assay was equal or superior
      to anti-HIV 1 and 2 tests run as references. The test was able to discriminate
      sera from patients with HIV infections from those from uninfected individuals
      with excellence; it also exerted high intra- and interassay precisions. The
      "modular" concept of the test allows the use of single components (gp32 or gp41)
      to separate between HIV-2 and HIV-1 infections, respectively.

PMID- 8150951
TI  - Sensitive quantitation of endotoxin by enzyme-linked immunosorbent assay with
      monoclonal antibody against Limulus peptide C.
AB  - Limulus peptide C, a 28-amino-acid fragment of coagulogen formed by the reaction
      of endotoxin with Limulus amebocyte lysate, was synthesized, and a monoclonal
      antibody against it was raised. A new microassay for endotoxin was developed,
      using this antibody in an enzyme-linked immunosorbent assay for generated peptide
      C-like immunoreactivity. A linear relationship between absorbance and endotoxin
      concentration was obtained. Control standard endotoxin in water could be detected
      to a level of 0.001 endotoxin unit per ml. The endotoxin levels in plasma samples
      from normal humans, rabbit, mice, and guinea pigs were generally found to be
      below the detection limit of 0.01 endotoxin unit per ml of plasma. The color and
      turbidity of specimens did not interfere with the assay. The consumption of
      Limulus amebocyte lysate in the assay was less than 5% of that in the gel-clot
      and chromogenic assays. With raw lysate, which was much more stable in solution
      than chloroform-treated lysate, the assay was still highly sensitive to endotoxin
      but was totally unresponsive to natural glucans. The monoclonal antibody cross
      reacted with peptide C-like immunoreactivity generated in Tachypleus amebocyte
      lysate, which gave equal sensitivity in the endotoxin assay.

PMID- 8150952
TI  - Monoclonal antibody to native P39 protein from Borrelia burgdorferi.
AB  - We have produced, by using a sonicate of Borrelia burgdorferi, a monoclonal
      antibody (MAb), NYSP39H, that is specific for the P39 protein band. This MAb
      reacted with 13 isolates of B. burgdorferi but not with eight different
      spirochetes (four borrelias, two leptospiras, and two treponemas). Surface
      labeling of B. burgdorferi with biotin and subsequent treatment with Nonidet P-40
      showed that P39 was not biotinylated but was extracted with Nonidet P-40,
      indicating that it is present within the outer membrane, but not on the surface
      of the spirochete. Immunoelectron microscopy revealed the immunogold probe
      primarily at the cytoplasmic membrane region of the spirochete. The MAb detected
      B. burgdorferi in the indirect fluorescent-antibody test only when the
      spirochetes from a culture or in a tick homogenate were fixed with polylysine and
      not with acetone. NYSP39H appears to be an appropriate probe for use in the
      specific detection of B. burgdorferi.

PMID- 8150953
TI  - Comparison of E test with standard broth microdilution for determining antibiotic
      susceptibilities of penicillin-resistant strains of Streptococcus pneumoniae.
AB  - We compared the E test (AB Biodisk North America, Inc., Culver City, Calif.) with
      the National Committee for Clinical Laboratory Standards broth microdilution
      method for the determination of MICs of penicillin and cefotaxime for 108
      isolates of Streptococcus pneumoniae. The E test was performed following
      manufacturer's recommendations with Mueller-Hinton blood agar, and the broth
      microdilution procedure was performed with lysed horse blood-supplemented Mueller
      Hinton broth. The microdilution method classified 26 isolates as highly
      penicillin resistant (MIC, > or = 2 micrograms/ml), 33 as intermediately
      resistant to penicillin (MIC, > or = 0.1 < 2.0 micrograms/ml), and 49 as
      susceptible to penicillin (MIC, < 0.1 micrograms/ml). Discordant results obtained
      with the E test for penicillin susceptibility testing compared with broth
      microdilution occurred for 19 of the 108 isolates tested. Cefotaxime MICs for 90%
      of isolates found highly resistant, intermediately resistant, and susceptible to
      penicillin by broth microdilution were 2.0, 0.5, and 0.06 micrograms/ml,
      respectively. There were 16 susceptibility category changes when the E test was
      used to determine cefotaxime MICs. All of the discrepancies in the penicillin and
      cefotaxime MICs determined by the E test occurred at the susceptibility category
      breakpoints, and all represented differences of only one twofold dilution factor.
      Properly performed and controlled, the E test should be a reliable quantitative
      procedure for more accurately predicting the susceptibility of S. pneumoniae to
      several antibiotics.

PMID- 8150954
TI  - Evaluation of differential inoculum disk diffusion method and Vitek GPS-SA card
      for detection of oxacillin-resistant staphylococci.
AB  - This study was conducted in order to compare the accuracy of detection of
      oxacillin-resistant staphylococci, defined by microdilution MICs, population
      analyses, and mec gene hybridization, with the Vitek GPS-SA Susceptibility Card
      with that of the standard inoculum (10(7) CFU) and high-inoculum (10(9) CFU) disk
      diffusion tests. By the standard inoculum disk diffusion test, 10 of 67 (15%)
      isolates of oxacillin-resistant Staphylococcus aureus and 3 of 47 (6%) isolates
      of Staphylococcus epidermidis were falsely susceptible after 24 h of incubation
      at 35 degrees C. By the high-inoculum disk diffusion test (10(9) CFU), 4 of the
      10 isolates of S. aureus remained falsely susceptible, whereas none of the
      isolates of S. epidermidis was falsely susceptible. Of the 10 isolates of S.
      aureus falsely susceptible by the standard disk test, only one remained falsely
      susceptible after an additional 24 h of incubation at 22 degrees C. All four
      isolates of S. aureus that were falsely susceptible by the high-inoculum disk
      diffusion test after 24 h of incubation at 35 degrees C became resistant after an
      additional 24 h of incubation at 22 degrees C. Thus, extended incubation of both
      the standard and high-inoculum disk diffusion tests increased their accuracy in
      detecting oxacillin resistance. All isolates of oxacillin-resistant staphylococci
      were accurately detected with the Vitek software upgrades (6.1 and 7.1) of the
      GPS-SA card.

PMID- 8150956
TI  - Genotypic variation and slime production among blood and catheter isolates of
      Candida parapsilosis.
AB  - Candida parapsilosis is an important nosocomial pathogen that can proliferate in
      high concentrations of glucose and form biofilms on prosthetic materials. We
      investigated the genotypic diversity and slime production among 31 isolates of C.
      parapsilosis from individual patients with bloodstream or catheter infections.
      DNA subtyping was performed by using electrophoretic karyotyping plus restriction
      endonuclease analysis with BssHII followed by pulsed-field gel electrophoresis.
      Slime production was evaluated by growing organisms in Sabouraud broth with 8%
      glucose and examining the walls of the tubes for the presence of an adherent
      slime layer. Overall there were 14 DNA subtypes among the 31 isolates. Eighty
      percent of the isolates produced slime; 67% of the isolates were moderately to
      strongly positive, 13% were weakly positive, and 20% were not slime producers.
      The ability of isolates of a given DNA type to produce slime under these
      conditions was variable. The results of these studies indicate moderate genotypic
      variation among clinical isolates of C. parapsilosis. The propensity of these
      isolates to form slime in glucose-containing solutions suggests that this
      phenotypic characteristic may contribute to the ability of C. parapsilosis to
      adhere to plastic catheters and cause infections.

PMID- 8150955
TI  - Serologic surveillance for the Lyme disease spirochete, Borrelia burgdorferi, in
      Minnesota by using white-tailed deer as sentinel animals.
AB  - To determine the effectiveness of white-tailed deer as sentinel animals in
      serologic surveillance programs for Borrelia burgdorferi, we performed enzyme
      linked immunosorbent assay (ELISA) and Western immunoblotting analyses on 467
      deer serum samples. The seropositivity rate in the ELISA was 5% for the 150
      samples collected at the three sites in which the tick Ixodes scapularis was
      absent. The three sites with established I. scapularis populations had a
      seropositivity rate of 80% for 317 samples. Results were similar for two closely
      situated sites, one with an established I. scapularis population and one without;
      these sites were only 15 km apart. Rates of seropositivity were significantly
      higher in yearling and adult deer than in fawns. The mean numbers of bands seen
      on Western immunoblots were 3.0 for samples negative in the ELISA and 13.8 for
      samples positive in the ELISA; all of these samples were collected from sites in
      which I. scapularis was established. At sites in which I. scapularis was absent,
      the mean numbers of bands seen were 1.6 for samples negative in the ELISA and 8.2
      for samples positive in the ELISA. There were 14 different B. burgdorferi
      antigens that reacted with more than 50% of the ELISA-positive samples from areas
      with I. scapularis. A 19.5-kDa antigen reacted with 94% of the ELISA-positive
      samples. Reactivity against OspA and OspB was weak a infrequent (2%). Serologic
      analysis of white-tailed deer sera appears to be an accurate and sensitive
      surveillance method for determining whether B. burgdorferi is present in specific
      geographic locations.

PMID- 8150957
TI  - Virulence of Rhodococcus equi isolates from patients with and without AIDS.
AB  - Rhodococcus equi is an emerging opportunistic pathogen of human immunodeficiency
      virus-infected patients. Thirty-nine isolates of R. equi from immunocompromised
      patients with and without AIDS were analyzed for the presence of virulence
      plasmid DNA, expression of 15- to 17-kDa antigens, and their pathogenicities in
      mice. Of the human isolates, eight contained an 85-kb virulence plasmid,
      expressed 15- to 17-kDa antigens, and were virulent in mice. Nineteen isolates
      carried cryptic plasmids of various sizes, and the remaining 12 isolates did not
      contain any plasmids. These 31 isolates did not express virulence-associated
      antigens and were not virulent in mice. The results suggested that opportunistic
      infections in immunocompromised patients could be caused by both virulent and
      avirulent R. equi strains and that the pathogenesis of R. equi infection in
      immunocompromised patients appears to be different from that which occurs in
      foals.

PMID- 8150958
TI  - A 2-year study of Helicobacter pylori in children.
AB  - From September 1990 to October 1992, Helicobacter pylori was searched for in 426
      children, 2 days to 16 years old, requiring upper fibroscopy for various
      symptoms. H. pylori was detected in 77 children (18.1%). Recurrent abdominal pain
      was present in 63.3% of the patients with H. pylori versus 48.6% of a control
      group of 74 age-matched children negative for H. pylori, weight loss was present
      in 6.5% of the patients versus 0% of the control subjects, and a family history
      of peptic ulcer was present in 14.2% of the patients versus 5.4% of the controls.
      Micronodular gastritis was observed in 31 children with H. pylori infection
      (40.2%). Among the 24 children (31.1%) with H. pylori infection and a normal
      mucosa at endoscopy, 18 (75%) complained of recurrent abdominal pain. H. pylori
      was also found in 21 of 38 children (55.2%) being examined because of short
      stature. These findings indicate that H. pylori should be looked for in children
      with recurrent abdominal pain with or without weight loss or a family history of
      peptic ulcer. Its relevance in short-stature syndrome requires further
      clarification.

PMID- 8150959
TI  - Loofah sponges as reservoirs and vehicles in the transmission of potentially
      pathogenic bacterial species to human skin.
AB  - Loofah sponges are natural products used as exfoliative beauty aids. As a
      consequence of tracing a case of Pseudomonas aeruginosa folliculitis to a
      contaminated loofah sponge, we assessed the role of loofah sponges in supporting
      the growth of a wide variety of bacterial species. Our data show growth
      enhancement of sterile loofah fragments for numerous gram-negative (Pseudomonas,
      Xanthomonas, and Klebsiella) and gram-positive (Enterococcus and group B
      Streptococcus) species of human and environmental origin. Furthermore, hydrated
      new, unused loofah sponges undergo a shift in bacterial flora from sparse
      colonies of Bacillus spp. and Staphylococcus epidermidis to a predominantly gram
      negative flora. The growth-promoting potential of loofah sponges (and other
      exfoliatives) can be further augmented by desquamated epithelial cells entrapped
      in the loofah fibrous matrix. Therefore, as loofah sponges (and other
      exfoliatives) can serve as a reservoir and a vehicle for the transmission of
      potentially pathogenic species to the human skin, we recommend their
      decontamination with hypochlorite (10%) bleach at regular intervals.

PMID- 8150960
TI  - Variation of DNA sequence in immediate-early gene of human herpesvirus 6 and
      variant identification by PCR.
AB  - The complete nucleotide sequence of one of the immediate-early genes of human
      herpesvirus 6 variant B was determined and compared with that of variant A
      reported by Martin et al. (M.D. Martin, J. Nicholas, B. J. Thomson, C. Newman,
      and R. W. Honess, J. Virol. 65:5381-5390, 1991). While it was reported that two
      open reading frames exist in this region of variant A, only one open reading
      frame was found in variant B and the putative coding region of variant B was
      2,679 nucleotides long. Furthermore, two additive regions of 108 and 228 bp were
      found in variant B. Primers covering one of these regions deleted in variant A
      were synthesized and used for PCR amplification. Twelve isolates from patients
      were clearly classified into variants A and B by PCR amplification with these
      primers. All isolates from patients with exanthem subitum were variant B.

PMID- 8150961
TI  - Rapid detection of parainfluenza virus type 3 RNA in respiratory specimens: use
      of reverse transcription-PCR-enzyme immunoassay.
AB  - Parainfluenza virus type 3 (PIV-3), an important lower respiratory tract pathogen
      in young children and immunocompromised individuals, may be underdiagnosed
      because of the insensitivity of available culturing systems and delay in
      identification of virus in cell culture. We developed a reverse transcription-PCR
      enzyme immunoassay (RT-PCR-EIA) for PIV-3, using primers specific for a highly
      conserved region of the hemagglutinin-neuraminidase gene. Testing of nasal washes
      spiked with PIV-3 or other respiratory viruses showed that this assay detected
      seven strains of PIV-3 but not other respiratory viruses. Of 103 respiratory
      tract samples obtained from children experimentally infected with a liver PIV-3
      vaccine or naturally infected with wild-type PIV-3, 51 were positive by culture
      and 48 were positive by RT-PCR-EIA. Eleven of the culture-positive samples were
      negative by RT-PCR-EIA; however, none of these grew virus upon reinoculation into
      cell culture, indicating that virus was lost or was present at a very low titer.
      Eight of the culture-negative samples were positive by RT-PCR-EIA: two were
      obtained from a subject who was culture negative but had a serologic response to
      PIV-3, four were obtained 7 to 9 days after the first positive culture, and two
      were obtained 1 day prior to the first positive culture. Thus, this RT-PCR-EIA
      for PIV-3 is sensitive and specific and can detect viral RNA in samples from
      which virus cannot be cultivated. This assay could be used for diagnosis late in
      the course of PIV-3 infection and for accurate detection of disease outbreaks.

PMID- 8150962
TI  - Ribotyping for differentiating Flavobacterium meningosepticum isolates from
      clinical and environmental sources.
AB  - On the basis of DNA-DNA hybridization data, two main genomic relatedness groups
      (I and II) have been reported for a geographically varied collection of 52
      strains of Flavobacterium meningosepticum. Herein, we have shown that genomic
      group II can be further divided into four subgroups (II:1 to II:4). To examine
      the taxonomic relevance of the ribosomal patterns of the 52 F. meningosepticum
      strains, the patterns were compared with existing DNA-DNA hybridization data with
      restriction enzymes PstI and HindIII. Ribotyping of the 52 F. meningosepticum
      strains showed banding patterns that could identify them correctly to one of the
      five genomic groups or subgroups. To assess the value of ribotyping for the
      interpretation of epidemiological data, the discriminatory power of the method
      was investigated for the 52 F. meningosepticum strains. With one to four
      restriction enzymes (PstI, HindIII, ClaI, EcoRI), a discriminatory index of 0.95
      to 0.97 was found. The value of ribotyping in an epidemiological setting was
      assessed for three clinical isolates of F. meningosepticum from an outbreak of
      meningitis and bacteremia in the neonatal intensive care unit, Rigshospitalet,
      Copenhagen, Denmark. The three clinical isolates were shown to belong to the same
      ribotype, characteristic of genomic subgroup II:1. This ribotyping method will
      prove to be a useful tool for epidemiological studies concerning F.
      meningosepticum in the future.

PMID- 8150963
TI  - Comparative evaluation of alternative methods for broth dilution susceptibility
      testing of fluconazole against Candida albicans.
AB  - A comparative evaluation of methods for broth macro- and microdilution
      susceptibility testing of fluconazole was conducted with 119 clinical isolates of
      Candida albicans. Macro- and microdilution testing were performed according to
      National Committee for Clinical Laboratory Standards recommendations. For
      reference macrodilution testing, an 80% inhibition endpoint (MIC 80%) was
      determined after 48 h of incubation in accordance with National Committee for
      Clinical Laboratory Standards proposed standard M27-P. Microdilution endpoints
      were scored as the first tube or well in which a prominent reduction in turbidity
      (score 2 out of a possible 4) was observed compared with the growth control
      (Micro MIC-2). Alternative endpoint criteria were assessed independently of the
      reference MIC 80% and Micro MIC-2 values and included a colorimetric
      microdilution endpoint determined by using an oxidation-reduction indicator
      (Alamar Blue; Alamar Bio-sciences Inc., Sacramento, Calif.). The MICs for the two
      microdilution test systems were read after 24 and 48 h of incubation. The
      percentage of fluconazole MICs within 2 doubling dilutions of the macrodilution
      reference values was 94% for both microdilution tests read at 24 h. Agreement was
      slightly lower at 48 h and ranged from 91 to 93%. Comparison of Micro MIC-2 and
      colorimetric microdilution MICs resulted in agreements of 97 and 93% at 24 and 48
      h, respectively. These results show excellent agreement among alternative methods
      for fluconazole susceptibility testing.

PMID- 8150964
TI  - Isolation of hepatitis C virus RNA from serum for reverse transcription-PCR.
AB  - Standard multistep extraction and isolation of RNA for hepatitis C virus (HCV)
      reverse transcription (RT)-PCR are impractical for routine use in clinical
      laboratories. We compared three simple commercially available methods for RNA
      isolation (RNAzol B, TRISOLV, and ULTRASPEC; Biotecx Laboratories, Houston, Tex.)
      and a total nucleic acid isolation method (IsoQuick; MicroProbe Corp., Garden
      Grove, Calif.) for the recovery of HCV RNA from sera obtained from 12 viremic
      patients for RT-PCR. RNAzol B, TRISOLV, ULTRASPEC, and IsoQuick extraction
      methods detected 87.5, 79.2, 33.3, and 58.3% of the paired positive samples,
      respectively. The method used for isolation of RNA is an important concern when
      optimizing HCV RT-PCR.

PMID- 8150965
TI  - Direct identification of Mycobacterium species in BACTEC 7H12B medium by high
      performance liquid chromatography.
AB  - Primary cultures of mycobacteria grown in BACTEC 7H12B medium (Becton Dickinson
      and Co., Paramus, N.J.), with and without the addition of oleic acid-albumin
      dextrose-catalase (OADC) enrichment (Becton Dickinson and Co., Cockeysville,
      Md.), were analyzed for their mycolic acid patterns by high-performance liquid
      chromatography. Of the 126 isolates grown in medium to which OADC was added, 117
      (93%) were successfully identified to the species level. The time to
      identification of Mycobacterium tuberculosis (n = 65) averaged 19 days, and the
      average time was 21 days for nontuberculosis mycobacteria (n = 52) from initial
      specimen processing. None of the 10 isolates cultured without OADC were
      identified. The mycolic acid patterns were considered reliable for identification
      if the height of the tallest peak in the chromatogram was at least 50% of the
      internal standard peak height.

PMID- 8150966
TI  - Suppression of fungal growth exhibited by Pseudomonas aeruginosa.
AB  - Three surgery patients were monitored postoperatively, with particular reference
      to lung infection. In each case there was a clinical impression that Pseudomonas
      aeruginosa suppressed the growth of Candida albicans in patients with clinically
      significant lung infections from whom both of these organisms were isolated from
      serial sputum samples. Regrowth of C. albicans after P. aeruginosa eradication
      occurred in two patients, despite fluconazole therapy, to which both C. albicans
      isolates were susceptible. In all three patients, the strain of P. aeruginosa was
      found to inhibit the growth of the corresponding C. albicans strain in vitro.
      Further in vitro susceptibility studies revealed significant inhibition by 10
      strains of P. aeruginosa of 11 strains of fungi known to infect humans; these
      were Candida krusei, Candida keyfr, Candida guillermondii, Candida tropicalis,
      Candida lusitaniae, Candida parapsilosis, Candida pseudotropicalis, Candida
      albicans, Torulopsis glabrata, Saccharomyces cerevisiae, and Aspergillus
      fumigatus.

PMID- 8150967
TI  - Improved PCR sensitivity for direct genotyping of Chlamydia trachomatis serovars
      by using a nested PCR.
AB  - Successful amplification of omp1 DNA by PCR is crucial in the genotyping of
      Chlamydia trachomatis when directly performed with clinical samples (J. Lan, J.
      M. M. Walboomers, R. Roosendaal, G. J. van Doornum, D. M. McLaren, C. J. L. M.
      Meijer, and A. J. C. van den Brule, J. Clin. Microbiol. 31:1060-1065, 1993).
      Several primers flanking the four variable domains of the omp1 gene were selected
      and tested for sensitivity in several nested PCRs with serial dilutions of
      serovar G. The optimal sensitivity obtained was 0.1 to 0.01 inclusion-forming
      units, similar to that obtained in the C. trachomatis plasmid PCR. With this
      approach, any C. trachomatis PCR-positive sample can be typed.

PMID- 8150968
TI  - Optical immunoassay for streptococcal pharyngitis: evaluation of accuracy with
      routine and mucoid strains associated with acute rheumatic fever outbreak in the
      intermountain area of the United States.
AB  - The Strep A OIA (BioStar, Inc., Boulder, Colo.) rapid detection system is an
      intriguing technology that utilizes an immunoassay relying on changes in
      reflected light to directly detect group A streptococcal antigen from specimens.
      In this evaluation, 424 routine pediatric throat specimens and 20 simulated
      oropharyngeal specimens with added mucoid (M type 3, 18) strains were cultured
      and tested by the Strep A OIA. The respective sensitivities and specificities
      were as follows: Strep A OIA versus enhanced broth culturing, 84.2 and 95.7%; and
      streptococcus-SXT agar (BBL Microbiology Systems, Cockeysville, Md.) culturing
      versus enhanced broth culturing, 82.9 and 98.6%. The Strep A OIA is an 8-min,
      technologist-friendly, accurate technique with an 89.4% agreement with
      traditional culturing.

PMID- 8150969
TI  - Purification of Chlamydia trachomatis strains in mixed infection by monoclonal
      antibody neutralization.
AB  - A Chlamydia trachomatis D* serovariant strain was found to be mixed with an F
      serovar strain in a clinical specimen. By using a monoclonal antibody which
      neutralizes serovar F infectivity in hamster kidney cells, the D* variant strain
      was enriched until it could be cloned by limiting dilution. This newly described
      neutralization enrichment procedure can be used to purify a C. trachomatis
      serovar present in small numbers in a mixed culture or, potentially, to identify
      nonneutralizable mutants.

PMID- 8150971
TI  - Treponemal infections in hares in The Netherlands.
AB  - Treponemal infections in wild European brown hares (Lepus europaeus) from The
      Netherlands were diagnosed by means of serological tests for human syphilis and
      histological demonstration of spirochetes by the Bosma-Steiner silver
      impregnation method in histological sections of skin lesions. The treponeme
      should probably be classified as "Treponema paraluisleporis."

PMID- 8150970
TI  - Rapid assay for detection of toxic shock syndrome toxin 1 from human sera.
AB  - A noncompetitive enzyme-linked immunosorbent assay that enables the quantitation
      of toxic shock syndrome toxin 1 (TSST-1) to as little as 30 pg/ml and the
      detection of TSST-1 to 10 pg/ml in phosphate-buffered saline including 33% human
      serum or plasma was developed. It takes only 3 h to complete this assay after
      plate preparation. In this study, 64 human serum samples obtained from 30
      patients with toxic shock syndrome or toxic shock syndrome-like symptoms were
      subjected to testing for the detection of TSST-1. With a cutoff level for TSST-1
      of less than 100 pg/ml, 28 samples obtained from 12 patients were positive for
      TSST-1. The mean and maximum concentrations for these TSST-1-positive samples
      were 440 and 5,450 pg/ml, respectively. Of these 12 patients, 8 were
      Staphylococcus aureus culture positive, 3 were negative upon bacterial culturing,
      and 1 had no cultures done.

PMID- 8150973
TI  - Early recognition of atypical Francisella tularensis strains lacking a cysteine
      requirement.
AB  - Seven cultures referred to in our laboratories as unidentified gram-negative
      bacilli or Haemophilus species were identified as atypical strains of Francisella
      tularensis lacking a requirement for cysteine or enriched medium for growth. The
      use of cellular fatty acid composition analysis facilitated early recognition of
      this pathogen and prompt implementation of appropriate biosafety measures.

PMID- 8150972
TI  - Microplate-based DNA hybridization assays for detection of human retroviral gene
      sequences.
AB  - Nonisotopic, microwell-based DNA hybridization assays for the specific detection
      of human immunodeficiency virus type 1 (HIV-1) gag, human T-cell lymphotropic
      virus type I (HTLV-I) pol, and HTLV-II pol DNA sequences were evaluated. The
      performances of these detection kits (Gene Detective enzyme oligonucleotide
      assays; Cellular Products, Inc., Buffalo, N.Y.) were assessed by using clinical
      samples whose infection status were established by amplification by PCR and then
      liquid hybridization detection by using virus-specific probes. Peripheral blood
      mononuclear cell lysates from 59 HIV-1-, 35 HTLV-I-, and 19 HTLV-II-infected
      individuals and from 15 healthy blood donors were used as substrates for PCR
      amplification. The results of the study demonstrated a clinical sensitivity of
      100%. In addition, the enzyme oligonucleotide assays were able to detect 1 to 10
      proviral copies subsequent to PCR amplification, indicating an analytical
      sensitivity comparable to that of liquid hybridization.

PMID- 8150974
TI  - Diagnosis of paracoccidioidomycosis by dot immunobinding assay for antibody
      detection using the purified and specific antigen gp43.
AB  - The dot immunobinding assay, a rapid, visually read test, was adapted for
      serodiagnosis and follow-up of paracoccidioidomycosis (PCM). Purified gp43
      antigen was tested before and after sodium metaperiodate treatment. To evaluate
      the assay, it was tested with sera from PCM, histoplasmosis, Jorge Lobo's
      disease, aspergillosis, candidiasis, and cryptococcosis patients and healthy
      subjects. Native gp43 gave positive results with all sera from PCM patients and
      weakly positive results with sera from Jorge Lobo's disease patients (31.3%). No
      false-positive results were obtained when periodate-treated gp43 was used as the
      antigen. These results indicate that the dot immunobinding test is sensitive,
      specific, economical, and fast for serodiagnosis and follow-up studies of PCM.

PMID- 8150975
TI  - Microflora of abdominal sepsis by locus of infection.
AB  - Specimens from 152 abdominal infections were examined to determine which groups
      of endogenous bacteria participate in infection emanating from different sites in
      the gastrointestinal tract. A notable finding was the predominance of anaerobic
      microflora from infections of ischemic versus perforated small bowel. Empiric
      antibiotic treatment for ischemic bowel should include focused coverage for
      anaerobes.

PMID- 8150976
TI  - Predictive accuracy of disk diffusion test for Proteus vulgaris and Providencia
      species against five newer orally administered cephalosporins, cefdinir,
      cefetamet, cefprozil, cefuroxime, and loracarbef.
AB  - Three members of the tribe Proteeae (Proteus vulgaris, Providencia rettgeri, and
      Providencia stuartii) were tested against five newer orally administered
      cephalosporins (cefdinir, cefprozil, cefuroxime, cefetamet, and loracarbef) by
      the disk diffusion and reference broth microdilution methods. One hundred strains
      of these organisms were tested to confirm the excessive interpretive error rates
      that previously had been noted for the disk diffusion test. The results indicate
      that the suggested disk diffusion breakpoints for cefetamet and cefuroxime were
      without serious interpretive errors. In contrast, loracarbef, cefdinir, and
      cefprozil results exceeded acceptable interpretive error rates, with very major
      (false-susceptible) errors of 4, 5, and 9% respectively. Loracarbef currently has
      a warning in the National Committee for Clinical Laboratory Standards table
      footnotes addressing this problem. We recommend including cefdinir and cefprozil
      in the list of compounds requiring this warning. In addition, MICs of cefazolin,
      cefaclor, and cephalothin were determined to establish whether a class MIC
      concept to predict susceptibility for these agents was possible. When the indole
      positive Proteus strains are tested, cefazolin MICs can be used to predict MICs
      of all tested orally administered cephems (8 to 13% total errors, with only a 0
      to 1% very major error.

PMID- 8150978
TI  - Effects of blood medium supplements on activities of newer cephalosporins tested
      against enterococci.
AB  - This comparative study determined the effect of blood on the antienterococcal
      activities of the newer cephalosporins. Standardized disk diffusion
      susceptibility tests were performed with 57 strains of enterococci (30
      Enterococcus faecalis strains) on Mueller-Hinton agar with and without 5% sheep
      blood supplementation. Twelve cephalosporins representing five different
      structural groups (based on the 7-alpha position substitution) were tested. The
      greatest frequency of activity enhancement by blood was observed with cefdaloxime
      and cefdinir (7-alpha hydroxyimino group) against E. faecalis. Cephalosporins
      with a 7-alpha methoxyimino group (cefpodoxime, cefepime, and cefpirome) had
      marked increases in zone diameters (3 to > 9 mm) when tested with the blood
      supplement. Cephems with 7-alpha amino or carboxy substitutions did not
      demonstrate any enhanced activity. Awareness of this phenomenon is important for
      the interpretation and accuracy of cephalosporin susceptibility testing.

PMID- 8150977
TI  - Case report of spinal epidural abscess caused by Haemophilus paraphrophilus.
AB  - Haemophilus paraphrophilus was recovered in pure culture from purulent material
      collected at surgery from a patient presenting with a spinal epidural abscess and
      a severe neurological deficit. This is the first report of such an occurrence.

PMID- 8150979
TI  - Improved performance of PACE 2 with modified collection system in combination
      with probe competition assay for detection of Chlamydia trachomatis in urethral
      specimens from males.
AB  - The Gen-Probe PACE 2 assay (GP) in combination with a modified collection system
      was compared with cell culture (CC) for the detection of Chlamydia trachomatis in
      urethral specimens from males. Analysis of discordant results was performed by
      PCR. The modifications, i.e., application of a more rigid swab type and a 50%
      reduction in the amount of transport medium, were made to improve the sensitivity
      of the assay. By using the modified GP on 302 urethral specimens from males, a
      sensitivity of 89.5% and a specificity of 100% were determined. In addition,
      performance of a probe competition assay on all GP samples with a result > 0.6
      and < 1.0 times the cutoff factor (gray zone) detected three more true-positive
      samples. The sensitivity of GP in combination with the probe competition assay
      increased to 94.9%, with a specificity of 100%. This was identical to the
      performance of CC. The modified GP offers a very sensitive and specific
      alternative to CC.

PMID- 8150980
TI  - Survival of human immunodeficiency virus in suspension and dried onto surfaces.
AB  - Cell-free and cell-associated human immunodeficiency virus cultures suspended in
      10% serum remained infectious for several weeks at room temperature. The
      stability was further increased when cell-associated virus was suspended in neat
      serum. When dried onto a glass coverslip, virus remained infectious for several
      days, although cell-associated virus lost infectivity more rapidly than cell-free
      virus.

PMID- 8150981
TI  - Nosocomial septicemia caused by Serratia plymuthica.
AB  - We report a case of nosocomial septicemia in a 79-year-old patient caused by
      Serratia plymuthica with no evident focus of infection. The patient was treated
      with gentamicin (40 mg every 8 h) during 10 days; clinical resolution of the
      infection was obtained after the 10-day treatment period.

PMID- 8150983
TI  - Lyme disease: the sensible pursuit of answers.

PMID- 8150982
TI  - Identification of Streptococcus suis isolated from swine: proposal for
      biochemical parameters.
AB  - A study was made of the biochemical profiles of 59 strains serotyped as
      Streptococcus suis, isolated from diseased and clinically healthy pigs. The
      following parameters are proposed for the identification of the species: Voges
      Proskauer negativity, hydrolysis of esculin positivity, trehalose positivity,
      negativity for growth in 6.5% NaCl, and absence of beta-hemolysis on sheep blood
      agar. S. suis serotype 2 is negative for hippurate, pyrrolidonylarylamidase, and
      mannose.

PMID- 8150984
TI  - Monoclonal antibody-based enzyme-linked immunosorbent assay for glycyrrhizin and
      its aglycon, glycyrrhetic acid.
AB  - Monoclonal antibodies (MoAbs) specific for glycyrrhetic acid (GA) were prepared
      and characterized. Obtained MoAbs (AGA-1, AGA-3, and AGA-6) reacted with GA dose
      dependently, but not with glycyrrhizin (GL), carbenoxolone, and steroids. Next,
      an enzyme-linked immunosorbent assay (ELISA) system using AGA-1 was established.
      The standard curve showed good linearity between 0.01 and 1000 ng/ml of GA, and
      the detection limit was 5 pg/ml. Recovery, and intra- and interassay variations
      of this assay system was satisfactory. GL was also measurable quantitatively
      after acid-hydrolysis of the samples. The developed ELISA system would be useful
      to determine GL and GA in biological samples or drugs as an alternative method to
      high performance liquid chromatography (HPLC).

PMID- 8150985
TI  - Subpicogram determination of oxytocin by an enzyme immunoassay using
      acetylcholinesterase as label.
AB  - The pure tetrameric form of Acetylcholinesterase (EC-3.1.1.7) from the electric
      eel electrophorus electricus has been covalently coupled to oxytocin. This
      conjugate has been used as tracer in a heterologous competitive immunoassay.
      Microtiter plates coated with a mouse monoclonal anti-rabbit immunoglobulin
      antibody were used to separate bound and free moieties of the tracer.
      Acetylcholinesterase activity bound to the solid phase was measured by a
      colorimetric assay. The minimum detectable concentration was 0.075 pg/well (ie
      1.5 pg/ml) and precision was less than 8% at concentration above 0.15 pg/well. An
      extraction step improved sensitivity up to 10 times with good recoveries. To
      assess the validity of this assay, basal levels of oxytocin were measured during
      the oestrous cycle of a cow.

PMID- 8150986
TI  - A comparison of two fixatives on IFA HEp-2 slides for the detection of
      antinuclear antibodies.
AB  - A comparative evaluation of two fixatives on HEp-2 slides that detect antinuclear
      antibodies via indirect immunofluorescence was undertaken. The sensitivities of
      these two methods were compared to determine which of the two is more efficient
      in screening for anti-SS-A (Ro) antibodies. Fixing HEp-2 cells with a pure
      acetone solution resulted in a 97.5% sensitivity when anti-SS-A (Ro) positive
      samples were tested while only an 81.3% sensitivity was seen on HEp-2 cells fixed
      in an alcohol/acetone solution when detecting anti-SS-A (Ro) antibodies. In sera
      with only anti-SS-A (Ro) antibodies present, the fluorescence was more pronounced
      on the acetone fixed slides which made it easier to read than the alcohol/acetone
      fixed slides.

PMID- 8150987
TI  - Immunoassay of circulating trypanosomal antigens in sleeping sickness patients
      undergoing treatment.
AB  - Sera from 99 patients infected with Trypanosoma brucei rhodesiense and undergoing
      treatment, were analyzed for circulating trypanosomal antigens using a sandwich
      antigen-trapping enzyme-linked immunosorbent assay (ELISA). Trypanosomal antigens
      were detected in 83 (84%) of the patients. Post-treatment antigen profile in 67
      patients showed five distinct patterns: in 48% of the patients antigen levels
      remained elevated throughout the time of hospitalisation and follow-up; in 31%,
      antigens dropped to the negative value by the second month; in 7.5%, antigens
      dropped to the negative level and became elevated afterwards; in 7.5%, antigen
      levels were negative initially, but later, became elevated and remained so
      throughout the observation period; in 6%, antigen levels remained below the
      negative value throughout. All patients who relapsed on follow-up had earlier
      shown evidence of elevated antigen profile. There were no cases of relapses among
      21 patients whose antigen levels dropped subsequent to treatment. This ELISA
      trypanosome antigen detection test could be useful in evaluating treatment
      success, when used together with parasitological diagnostic techniques.

PMID- 8150988
TI  - Sensitivity of immunoenzymometric assay and detection method of enzyme.
AB  - The effect of the detection limit of an enzyme measurement on the detection limit
      of the immunoenzymometric assay (IEMA) was investigated. Using a biotin-labelled
      antibody and avidin-biotin alkaline phosphatase complex (ABC enzyme) reagent,
      three IEMA systems for interferon-gamma with different enzyme substrates for
      colorimetric, fluorometric, or chemiluminometric detection were developed. The
      optimum amounts of the reagents, the non-specific binding (NSB) level, and the
      detection limit of the IEMA were estimated. The results of this study suggest
      that the biotin-labelled antibody and ABC enzyme reagent should not decrease to
      less than 20 times the concentration of its Kd value and to less than 250 times
      the enzyme activity of the NSB, respectively. The detection limit of IEMA did not
      decrease as much as that of enzyme measurement because of lack of proportionate
      decrease of the NSB level. These findings should be very useful not only for IEMA
      but also for immunoblotting and immunocytochemistry research.

PMID- 8150989
TI  - DSM-IV: empirical, accessible, not yet ideal.

PMID- 8150990
TI  - Ecology and mental health.

PMID- 8150991
TI  - Rediscovering opportunities in the emerging health service environment.

PMID- 8150992
TI  - Pattern analysis in psychotherapy: a classical extinction paradigm.

PMID- 8150993
TI  - Psychology's role in a national health program.
AB  - Despite APA's virulent opposition to managed care, the reality is that with the
      forthcoming universal health coverage, managed care in some form is going to be
      central to whatever specific plan is adopted. The American Psychological
      Association has done the profession a great disservice by its unrelenting attacks
      on managed care. During the years that psychology could have played a role in
      shaping managed care, APA has sat on the sidelines simply carping at these new
      developments in the health care marketplace. Psychologists must recognize the
      reality of these changes and adapt to them, or we will find ourselves in the next
      5 to 10 years in a health profession that time has passed by.

PMID- 8150994
TI  - Neuropsychological measures and event-related potentials in alcoholics:
      interrelationships, long-term reliabilities, and prediction of resumption of
      drinking.
AB  - Sober male and female alcoholics and peer controls were tested and then retested
      14 months later on neuropsychological performance tests (NTP) and also had event
      related potentials (ERPs) recorded (non-concurrently) to visual stimulation. Both
      NTP and ERP measures distinguish male alcoholics from peer controls at test and
      retest; NTP, but not ERP, scores distinguish female alcoholics from peer
      controls. Both measures manifest moderate to high reliabilities over time and are
      correlated modestly. NTP and ERP measures obtained at the end of treatment
      predict future resumers and abstainers 8 to 14 months later. The results
      demonstrate the utility of biopsychological approaches to alcoholism and support
      Grant's (1986) concept of alcoholics as suffering from an intermediate duration
      (subacute) organic mental disorder.

PMID- 8150995
TI  - Ward Halstead's contributions to neuropsychology and the Halstead-Reitan
      Neuropsychological Test Battery.
AB  - This paper reviews the roots from which Halstead began his investigations, the
      significance of his original collaboration with neurological surgeons, and the
      long-term implications of his practical approach of observing brain-damaged
      patients in their everyday living situations in order to identify the problems
      and limitations they experienced. This work led to development of the Halstead
      Reitan Battery (HRB), which has proved to be sensitive to a broad range of
      neurological variables including location, type, and status of brain lesion. The
      HRB, in turn, has laid the groundwork for a rehabilitation program (REHABIT) that
      integrates neuropsychological evaluation with cognitive retraining, using an
      approach that can be designed to restore the individual's functional ability
      structure (as contrasted with approaches oriented toward highly specific deficits
      or toward a general, nonspecific notion of "brain damage."

PMID- 8150996
TI  - Psychology in a medical school: a personal account of a department's 35-year
      history.
AB  - In 1911 John Broadus Watson and Shepard Ivory Franz proposed that the teaching of
      psychology was as essential to the education of medical students as were anatomy,
      pharmacology, surgery, and the other basic and clinical sciences. Today, our
      country's 126 medical schools each employ an average of some 35 full-time faculty
      psychologists; 6 have established full-fledged departments of psychology that are
      comparable (administratively) to departments that include faculty from the more
      traditional basic and clinical sciences. Thirty-five years ago (in 1957) the
      University of Oregon Medical School was the first medical school to create a
      department of Medical Psychology. The present writer was hired that year to chair
      that newly established department and has served continuously in that capacity
      since then. This Presidential Address to the APA Division of the History of
      Psychology offers the writer's personal perspective on the history and
      development of that department during its first 35 years of existence.

PMID- 8150997
TI  - CAVEing the MMPI for an Optimism-Pessimism Scale: Seligman's attributional model
      and the assessment of explanatory style.
AB  - Research based on Seligman's model indicates that a pessimistic explanatory style
      predicts increased frequency of depression, poorer physical health, and lower
      levels of achievement. The data show that persons who have a pessimistic outlook
      on life are more frequent users of the medical and mental health care delivery
      systems. This paper describes the development of a bipolar MMPI Optimism
      Pessimism (PSM) scale that is based on the results of a technique--Content
      Analysis of Verbatim Explanation (CAVE)--applied to the MMPI. Reliability and
      validity indices show that the PSM scale is highly accurate and consistent with
      Seligman's theory. Identification of the patient's explanatory style may lead to
      improved management because intervention measures can be directed more accurately
      according to the patient's personality style. The new scale also will allow
      researchers to use existing MMPI data to explore relationships between
      explanatory style and various outcome variables and behavioral correlates.

PMID- 8150998
TI  - Issues in the design and analysis of controlled clinical trials.
AB  - Several issues that pertain to the analysis of data from repeated measurements
      designs are addressed. The necessity for an assumption concerning uniformity of
      correlations (symmetry) can be avoided by calculating linear and/or nonlinear
      trend scores. In the usual repeated measurements ANOVA the baseline covariate
      does not affect within-subject sums of squares, such as that for the groups x
      times interaction. However, the separately calculated trend scores have the
      advantage of accounting for most of that interaction and permitting covariance
      correction for baseline differences. Chance baseline differences in a repeated
      measurements design otherwise can contribute materially to probabilities of
      erroneous conclusions. A conservative criterion for use of one-sided tests of
      significance is proposed.

PMID- 8150999
TI  - Cytochromes in psychopharmacology.

PMID- 8151000
TI  - Buprenorphine effects on morphine- and cocaine-induced subjective responses by
      drug-dependent men.
AB  - The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on
      reports of subjective effects after single intravenous doses of morphine (10 mg),
      cocaine (30 mg), and saline placebo were studied on an inpatient clinical
      research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III
      R). Latency to detection and certainty of a drug effect, as well as drug quality
      (intensity, euphoria, and dysphoria), were studied before and after 10 to 12 days
      of buprenorphine maintenance. Saline was accurately identified by all 26 patients
      during the drugfree baseline and by 25 patients during buprenorphine maintenance
      conditions. All patients accurately identified morphine during the drugfree
      period before treatment with buprenorphine, but 18 (69%) of 26 patients were
      unable to detect morphine during buprenorphine maintenance and 2 misidentified
      morphine as cocaine. Six men (23%) accurately identified morphine and reported
      that the intensity and quality of morphine's effects were equivalent to drugfree
      conditions. Cocaine levels in plasma 5 minutes after intravenous cocaine
      injection were equivalent before and during buprenorphine treatment and averaged
      282.8 +/- 43.6 and 295.2 +/- 28.8 ng/ml during 4 and 8 mg/day of buprenorphine
      maintenance, respectively. All patients accurately identified cocaine before and
      during buprenorphine maintenance, and there were no significant changes in
      latency to detection and certainty of a drug effect or reports of cocaine-induced
      intensity or euphoria during buprenorphine treatment. The concordance between
      responses to morphine and cocaine during inpatient buprenorphine maintenance and
      drug use during the first 4 weeks of outpatient buprenorphine treatment was also
      examined in 16 men. The effects of buprenorphine on individual responses to an
      acute intravenous dose of morphine or cocaine during the inpatient study did not
      reliably predict the frequency of heroin or cocaine self-administration during
      the first 4 weeks of daily outpatient buprenorphine maintenance.

PMID- 8151001
TI  - Relationship between concentrations of adinazolam and its primary metabolite in
      plasma and therapeutic/untoward effects in the treatment of panic disorder.
AB  - Adinazolam mesylate, a triazolobenzodiazepine with antidepressant and anxiolytic
      activity, has been shown in several studies to treat panic disorder effectively.
      This report presents the results of analysis of concentrations in plasma of
      adinazolam and its primary metabolite, N-desmethyladinazolam (NDMAD), determined
      as a part of a flexible-dose, double-blind study of the efficacy of adinazolam
      mesylate sustained release tablets in the treatment of panic disorder with
      agoraphobia. Dosages administered in the study were titrated from 30 mg/day up to
      a maximum of 120 mg/day. Concentrations in plasma were determined by high
      performance liquid chromatography at clinical evaluations at the end of treatment
      weeks 1, 2, and 4. The concentrations of both compounds were proportional to the
      administered dose. An inverted U-shaped concentration-response curve was
      apparent, where response was based on a priori definitions contained in the study
      protocol. However, this was probably a result of the flexible-dose study design
      used. By use of the post hoc definitions of response, as measured by the
      Clinician's Global Improvement Scale and the total panic attack frequency,
      logistic regression analysis resulted in more adequate predictions of actual
      response frequencies. Results indicate that NDMAD contributes to the therapeutic
      effects of adinazolam mesylate sustained release tablets in the treatment of
      panic disorder. The exact contributions of adinazolam and NDMAD to response in
      panic disorder could not be determined, because of the correlation between
      adinazolam and NDMAD concentrations on multiple dosing.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8151002
TI  - Nicotine skin patch treatment increases abstinence, decreases withdrawal
      symptoms, and attenuates rewarding effects of smoking.
AB  - A variety of studies have shown that nicotine skin patches are effective in
      promoting smoking cessation. This study replicated this effect, in addition,
      nicotine skin patches were found to decrease a variety of withdrawal effects,
      including craving for cigarettes, negative affect, hypoarousal, and increased
      appetite. This study also assessed the depressive symptoms shown by smokers
      before and after they quit smoking. Control subjects showed a significant
      increase in depressive symptoms after smoking cessation, whereas the subjects
      given the nicotine skin patch were not as affected. If the subjects slipped and
      smoked a cigarette during the time they were wearing the patch, they were asked
      to rate the effects of that cigarette. These "slip" cigarettes were rated
      significantly lower in satisfaction and good taste by subjects in the nicotine
      patch group than by controls. The nicotine skin patch may improve smoking
      cessation rates both by reducing nicotine withdrawal effects and by reducing the
      reward of slips back to smoking. This latter effect may prove to be effective in
      preventing slips from turning into relapses.

PMID- 8151003
TI  - Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the
      role of pressor amines in beer.
AB  - A case report of a hypertensive crisis resulting from the ingestion of tap beer
      in a patient on an irreversible monamine oxidase inhibitor (MAOI; phenelzine)
      stimulated the investigation of different kinds of beer for tyramine
      concentration. The objective was to determine the tyramine concentration in tap
      and bottled beers. A total of 98 beer samples (79 different brands of beer) were
      analyzed by high-performance liquid chromatography for tyramine. Of these 98
      beers, 49 were bottled or canned beers and 49 were beers on tap. All of the
      bottled beers analyzed had safe tyramine concentrations (< or = 10 mg/liter;
      range, 0 to 3.16 mg/liter) and, thus, do not require restriction in patients
      receiving MAOIs. Therefore, the consumption of canned or bottled beer, including
      dealcoholized beer, in moderation (fewer than four bottles or cans; 1.5 liters
      within a 4-hour period) appears to be safe and does not require restriction in
      patients receiving MAOIs. Only 4 of 98 beer samples studied were found to have a
      dangerous (> 10 mg/liter) tyramine concentration, one of which was the index
      beer. The tyramine concentration in these four beers ranged from 26.34 to 112.91
      mg/liter. All four of these beers were tap beers produced by bottom fermentation
      (lagers) and brewed by a secondary fermentation process. Although we did not find
      any visible bacterial growth in the tap beers with high tyramine content, this
      finding does not preclude the possibility that bacterial contamination, bacterial
      growth, production of tyramine, and eventually bacterial death occurred at some
      earlier time. Therefore, to err on the side of caution, it is recommended that
      patients on irreversible MAOIs avoid beers on tap.

PMID- 8151004
TI  - New psychotherapeutic drugs.
AB  - Many new psychotherapeutic drugs are being developed for the major clinical
      indications for which they might be useful. As usual, we hope not only to obtain
      better drugs but also to posit hypotheses based on the presumed mode of action of
      effective drugs. Thus, we have a chance to test the role of serotonin, via the
      5HT1A receptor, in anxiety or to test the possible significance of multiple
      benzodiazepine receptors. Among antidepressant agents, we have a chance to
      determine the relative roles of norpinephrine and serotonin in the pathogenesis
      of these disorders. We may also determine whether antidepressant actions involve
      a number of aminergic neurotransmitters. Among antipsychotic drugs, the
      importance of dopamine D2 receptor blockade has diminished with the advent of
      atypical drugs affecting a variety of other receptors. It might also be possible
      to delineate more clearly the role of serotonin in psychosis. The GABA hypothesis
      of mania can be tested in a number of ways by current drugs. The role of calcium
      antagonism remains to be demonstrated. The acetylcholine hypothesis of
      Alzheimer's disease will be tested further by new compounds under trial. However,
      it seems increasingly doubtful that current drugs under test will explicate the
      current hypothesis of the abnormal processing of beta-amyloid precursor protein
      in that disorder. Thus, we hope, as we have for the past three decades, to be
      able to use drugs not only to treat, but also to generate hypotheses. It is a
      kind of bootstrapping enterprise, but our ultimate hope is not only to be better
      able to treat our patients, but also to better understand their afflictions.

PMID- 8151005
TI  - Duration of antidepressant trials: clinical and research implications.
AB  - The objective of our study was to demonstrate that additional antidepressant
      benefit occurs between weeks 4 and 6 in adult outpatients, even when dose is not
      increased. Response between weeks 4 and 6 was studied among depressed outpatients
      randomly assigned to imipramine, phenelzine, or placebo under double-blind
      conditions. Patients were selected for analysis only if they did not have a dose
      increase after the start of the fourth week of treatment (day 22). Eighty-eight
      patients met this condition. Conditional probability analysis was performed.
      Nonresponders to 4 weeks (28 days) of treatment had a significantly greater
      likelihood of responding by week 6 if they were on phenelzine rather than
      placebo. The same is probably true for patients on imipramine. In research and
      clinical care, 4 weeks is too short a trial of phenelzine to conclude a lack of
      efficacy. Four weeks is probably also too short a trial of imipramine.

PMID- 8151006
TI  - Concomitant use of valproate and carbamazepine in bipolar and schizoaffective
      disorders.
AB  - From pharmacy records, the authors identified 17 consecutive patients who were
      treated with carbamazepine and valproate simultaneously. Twelve patients were
      diagnosed with bipolar disorder, manic or mixed types; four patients received a
      diagnosis of schizoaffective disorder, manic type; and one had major depression
      and posttraumatic stress disorder. All 12 bipolar patients had a moderate to
      marked response to the combination drug treatment, whereas all 4 schizoaffective
      patients failed to respond. Only two patients had minor side effects. The authors
      conclude that the combination of valproate and carbamazepine is usually well
      tolerated and that it can be effective in bipolar patients who have previously
      failed to respond to anticonvulsant monotherapy.

PMID- 8151007
TI  - The use of the reversible monoamine oxidase-A inhibitor brofaromine in social
      phobia complicated by panic disorder with or without agoraphobia.

PMID- 8151008
TI  - Fluvoxamine treatment of body dysmorphic disorder.

PMID- 8151009
TI  - Behavioral side effects in obsessive-compulsive patients treated with
      fluvoxamine: a clinical description.

PMID- 8151010
TI  - Buspirone in combat-related posttraumatic stress disorder.

PMID- 8151011
TI  - Valproate treatment of comorbid panic disorder and affective disorders in two
      alcoholic patients.

PMID- 8151012
TI  - Changes in prostaglandin E2 and F2 alpha during vitellogenesis in the Florida
      crayfish Procambarus paeninsulanus.
AB  - While the role of eicosanoids in reproduction in vertebrate species has been well
      established, the role of these fatty acid derivatives in invertebrate species has
      not been as well characterized. The purpose of this study was to investigate
      changes in prostaglandins E2 and F2 alpha during vitellogenesis in the crayfish
      Procambarus paeninsulanus. In homogenates of crayfish ovaries taken at various
      stages of development, the rate of prostaglandin synthesis and the concentrations
      of prostaglandins E2 and F2 alpha increased during the final stages of yolk
      production just prior to ovulation. A gradual increase in prostaglandin E2
      amounts was observed throughout the progression of vitellogenesis. The data
      suggests the possible involvement of prostaglandins in regulatory events
      associated with vitellogenesis and the induction of ovulation in Procambarus
      paeninsulanus.

PMID- 8151013
TI  - Metabolism, thermogenesis and daily rhythm of body temperature in the wood
      lemming, Myopus schisticolor.
AB  - Wood lemmings (Myopus schisticolor) were captured during their autumnal migration
      in September and October. The animals were maintained at 12 degrees C and under
      12L:12D photoperiod. Basal metabolic rate and thermogenic capacity of the wood
      lemming were studied. Basal metabolic rate was 3.54 ml O2.g-1.h-1, which is 215
      238% of the expected value. The high basal metabolic rate seems to be typical of
      rodents living in high latitudes. The body temperature of the wood lemming was
      high (38.0-38.8 degrees C), and did not fluctuate much during the 24-h recording.
      The high basal metabolic rate and the high body temperature are discussed with
      regard to behavioural adaptation to a low-quality winter diet. Thermogenic
      capacity, thermal insulation and non-shivering thermogenesis of the wood lemming
      displayed higher values than expected: 53.0 mW.g-1, 0.53 mW.g-1.degrees C-1 and
      53.2 mW.g-1, respectively. Brown adipose tissue showed typical thermogenic
      properties, although its respiratory property was fairly low, but mitochondrial
      protein content was high compared to other small mammals. The 24-h recording of
      body temperature and motor activity did not reveal whether the wood lemming is a
      nocturnal animal. Possibly, the expression of a circadian rhythm was masked by
      peculiar feeding behaviour. It is concluded that the wood lemming is well adapted
      to living in cold-temperature climates.

PMID- 8151014
TI  - Quinidine-sensitive K+ channels in the basolateral membrane of embryonic
      coprodeum epithelium: regulation by aldosterone and thyroxine.
AB  - Basolateral K+ channels and their regulation during aldosterone- and thyroxine
      stimulated Na+ transport were studied in the lower intestinal epithelium
      (coprodeum) of embryonic chicken in vitro. Isolated tissues of the coprodeum were
      mounted in Ussing chambers and investigated under voltage-clamped conditions.
      Simultaneous stimulation with aldosterone (1 mumol.l-1) and thyroxine (1 mumol.l
      1) raised short-circuit current after a 1- to 2-h latent period. Maximal values
      were reached after 6-7 h of hormonal treatment, at which time transepithelial Na+
      absorption was more than tripled (77 +/- 11 microA.cm-2) compared to control (24
      +/- 8 microA.cm-2). K+ currents across the basolateral membrane were investigated
      after permeabilizing the apical membrane with the pore-forming antibiotic
      amphotericin B and application of a mucosal-to-serosal K+ gradient. This K+
      current could be dose dependently depressed by the K+ channel blocker quinidine.
      Fluctuation analysis of the short-circuit current revealed a spontaneous and a
      blocker-induced Lorentzian noise component in the power density spectra. The
      Lorentzian corner frequencies increased linearly with the applied blocker
      concentration. This enabled the calculation of single K+ channel current and K+
      channel density. Single K+ channel current was not affected by stimulation,
      whereas the number of quinidine-sensitive K+ channels in the basolateral membrane
      increased from 11 to 26.10(6).cm-2 in parallel to the hormonal stimulation
      transepithelial Na+ transport. This suggests that the basolateral membrane is a
      physiological target during synergistic aldosterone and thyroxine regulation of
      transepithelial Na+ transport for maintaining intracellular K+ homeostasis.

PMID- 8151015
TI  - The thyroid and photoperiodic control of seasonal reproduction in American tree
      sparrows (Spizella arborea).
AB  - To explore the role of the thyroid gland in the control of seasonal reproduction
      in obligately photoperiodic American tree sparrows (Spizella arborea), the
      effects of (1) thyroxine administered in drinking water to thyroid-intact
      photosensitive or photorefractory birds, and (2) radiothyroidectomy before and
      after photostimulation and during photorefractoriness were examined. Chronic
      administration of pharmacological doses of thyroxine induced testicular growth
      and usually regression in initially photosensitive birds held on short or
      intermediate daylengths. Some thyroxine-treated birds with regressed testes were
      absolutely photorefractory, but most remained photosensitive. Exogenous thyroxine
      never induced testicular growth in photorefractory birds moved to short days,
      though it often impeded, and sometimes even blocked, the recovery of
      photosensitivity. Although circumstantial, these effects of exogenous thyroxine
      are consistent with an hypothesis that assigns to thyroid hormones two roles--one
      stimulatory and the other inhibitory--in the control of seasonal reproduction.
      Radiothyroidectomy before photostimulation inhibited (but did not prevent)
      photoinduced testicular growth, blocked spontaneous testicular regression,
      suppressed molt, and prevented photorefractoriness. Moreover, as demonstrated by
      testicular growth after thyroxine replacement therapy, radiothyroidectomy during
      photorefractoriness later restored photosensitivity despite continued
      photostimulation. Thus, euthyroidism is an essential condition for maximizing
      (but not for initiating) photoinduced testicular growth and for triggering and
      maintaining photorefractoriness in photostimulated tree sparrows. However, when
      performed early during photostimulation, radiothyroidectomy neither immediately
      induced nor later blocked spontaneous testicular regression. Thus, endogenous
      thyroid hormones and long days may interact during a critical period to program a
      sequence of physiological events that plays out as photorefractoriness in
      chronically photostimulated birds. Such an organizational event cannot be
      permanent, for seasonal reproduction is episodic and its control mechanism
      necessarily cyclic. Because thyroidectomy simulated the well-known restorative
      effect of short days (and exogenous thyroxine impeded it), short days may
      dissipate photorefractoriness by creating a milieu wherein thyroid hormones are
      deficient or inactive.

PMID- 8151016
TI  - Recovery after anaerobic metabolism in the leech (Hirudo medicinalis L.).
AB  - Medicinal leeches (Hirudo medicinalis L.) responded to self-induced hypoxia (72
      h) with typical anaerobic metabolism characterized by a decrease in adenylate
      energy charge, utilization of the substrates glycogen and malate, and
      accumulation of the main anaerobic end-products succinate and propionate.
      Propionate was also excreted into the medium. Ammonia excretion was suppressed.
      Aerobic recovery resulted in a profound O2 debt. Resynthesis of ATP was completed
      within 30 min. Disposal of succinate and restoring of malate required 2-3 h, and
      clearance of propionate and recharging of glycogen 6-12 h. Ammonia excretion did
      not exceed normoxic rates and excretion of propionate during recovery accounted
      for only 10% of total propionate accumulated during hypoxia. It is postulated
      that the clearance of succinate and propionate involves oxidation but also
      resynthesis of malate and glycogen. During hypoxia and recovery blood osmolality
      remained constant. The Na+ and Cl- ion concentrations in blood, the decrease of
      which was nearly equimolar during hypoxia, were re-established following
      different time-courses. Na+ concentration returned to normoxic levels after 2-3
      h. The delayed increase in Cl- concentration, however, correlating with 6-12 h
      necessary to clear blood propionate, is interpreted as an anion regulating
      effect.

PMID- 8151017
TI  - Regulation of a voltage-dependent, calcium-activated K conductance by cyclic GMP
      in dissociated flounder enterocytes.
AB  - Enterocytes from the winter flounder (Pseudopleuronectes americanus) were
      isolated by collagenase digestion and maintained in flounder Ringer's solution.
      Whole cell currents were studied using the amphotericin-perforated whole-cell
      patch clamp technique. The mean resting membrane potential and capacitance values
      or dissociated cells were -45 +/- 7 mV and 5 +/- 0.4 pF, respectively.
      Enterocytes held at -20 mV and treated with 1 mumol.l-1 ionomycin exhibited
      outward currents when cells were stepped through a series of voltages from -60 to
      +110 mV. The reversal potential of this current in flounder Ringer's solution was
      -55 mV and the voltage at which half-maximal activation occurred was +20 mV.
      Voltage-dependent inhibition of outward current was observed at +60 mV and above.
      When cells were bathed in symmetric K Ringer's solution the reversal potential
      shifted to zero mV and no inhibition of current was observed at voltages between 
      60 and 140 mV. When the holding potential of the cell was changed from -20 to -80
      mV and stepped from -60 to +110 mV, a second [previously characterized, O'Grady
      et al. (1991)] K current with delayed-rectifier properties was identified. This
      observation demonstrated that the delayed rectifier K channel and the Ca(2+)
      activated K channel described in this study exist in the same cell. Extracellular
      addition of 2 mmol.l-1 Ba2+ to cells bathed in symmetric K Ringer's solution
      resulted in nearly complete inhibition of outward current. Charybdotoxin produced
      only minor effects on this current.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151018
TI  - Metabolic depression and Na+/K+ gradients in the aestivating Australian
      goldfields frog, Neobatrachus wilsmorei.
AB  - During aestivation the metabolic rate of the Australian goldfields frog
      Neobatrachus wilsmorei was reduced by 80% from its standard metabolic rate. The
      in vitro rate of oxygen consumption of isolated muscle and skin from aestivating
      frogs was up to 50% lower than that of the non-aestivating frogs. This in vitro
      rate of oxygen consumption was maintained for 6-12 h, indicating an intrinsic
      metabolic depression of tissues during aestivation. Frogs became dehydrated
      during aestivation. Muscle, skin and liver also became dehydrated during
      aestivation, but brain and kidney did not. Na+ and K+ contents and extracellular
      space measurement for muscle indicated that ion gradients were maintained across
      the muscle cell membrane during aestivation. Increases in plasma concentrations
      of Na+ and K+ were matched with similar increases in muscle intracellular ion
      concentrations. Extracellular space measurements were unsuccessful in the other
      tissues, but K+ content in all tissues (per dry weight) was maintained during
      aestivation, and the concentration of plasma K+ did not increase above that which
      can be accounted for by dehydration, indicating that K+ gradients were
      maintained.

PMID- 8151019
TI  - Comparative thermoregulatory adaptations of field mice of the genus Apodemus to
      habitat challenges.
AB  - Thermoregulatory abilities, which may play a role in physiological adaptations,
      were compared between two field mouse species (Apodemus mystacinus and A.
      hermonensis) from Mount Hermon. While A. hermonensis is common at altitudes above
      2100 m, A. mystacinus is common at 1650 m. The following variables were compared
      in mice acclimated to an ambient temperature of 24 degrees C with a photoperiod
      of 12L:12D, body temperature during exposure to 4 degrees C for 6 h, O2
      consumption and body temperature at various ambient temperature, non-shivering
      thermogenesis measured as a response to a noradrenaline injection, and the daily
      rhythm of body temperature. Both species could regulate their body temperature at
      ambient temperatures between 6 and 34 degrees C. The thermoneutral zone for A.
      mystacinus lies between 28 and 32 degrees C, while for A. hermonensis a
      thermoneutral point is noted at 28 degrees C. Both species increased O2
      consumption and body temperature as a response to noradrenalin. However, maximal
      VO2 consumption as an response to noradrenaline and non-shivering thermogenesis
      capacity were higher in A. mystacinus, even though A. hermonensis is half the
      size of A. mystacinus. The body temperature rhythm in A. hermonensis has a clear
      daily pattern, while A. mystacinus can be considered arhythmic. The results
      suggest that A. hermonensis is adapted to its environment by an increase in
      resting metabolic rate but also depends on behavioural thermoregulation. A.
      mystacinus depends more on an increased non-shivering thermogenesis capacity.

PMID- 8151020
TI  - An overview of oral health status, resources, and care delivery.

PMID- 8151021
TI  - Access to oral health and health care reform--inside the President's Task Force.

PMID- 8151022
TI  - Building on a strong foundation.

PMID- 8151023
TI  - The Coalition for Oral Health's position on health care reform.

PMID- 8151024
TI  - A tension between two cultures ... dentistry as a profession and dentistry as
      proprietary.

PMID- 8151025
TI  - Implications for state and local dental programs and relationships between public
      and private dental practice.

PMID- 8151026
TI  - The dental health care system and minority patients.

PMID- 8151027
TI  - Patients, parents, and providers as partners for care.

PMID- 8151028
TI  - Health care reform and oral medicine.

PMID- 8151029
TI  - Some suggestions for dentistry.

PMID- 8151030
TI  - Follow-up recommendations for patients with stage I malignant melanoma.
AB  - The objective of follow-up examinations of patients who have had Stage I invasive
      malignant melanoma is the early detection of local recurrences, metastases, and
      new primary melanomas. Model schedules for follow-up intervals were developed
      based on a survey of eight physicians. These melanoma experts agree that regular
      follow-up examinations are indicated and that the time intervals between
      examination vary according to the thicknesses of the melanomas. The patient
      follow-up schedule derived is: for melanomas up to 0.75-mm thick, every 6 months
      for years 1 and 2, and annually for years 3, 4, and 5; for melanomas 0.76-1.50 mm
      thick, every 3 months for years 1 and 2, semi-annually for years 3, 4, and 5; and
      for melanomas > 1.50 mm thick, every 3 months for years 1, 2, and 3, and semi
      annually for years 4 and 5. After the fifth year, the recommendation is to
      examine all patients annually for life because of the continued risk for
      recurrences and new primary melanomas. For those individuals at especially high
      risk for developing multiple primary melanomas more frequent examinations may be
      appropriate.

PMID- 8151031
TI  - Recalling basal cell carcinoma patients. A regional survey.
AB  - BACKGROUND: Patients with a basal cell carcinoma (BCC) are at increased risk for
      developing further BCCs, and long-term follow-up has been recommended to detect
      new cancers at an earlier, more easily treatable stage. The majority of BCCs are
      treated by dermatologists in their offices; we do not know to what extent they
      perform long-term follow up on their patients. OBJECTIVE: To determine how
      practicing dermatologists follow up their BCC patients. METHODS: A mailed
      questionnaire survey of 166 practicing members of a regional dermatologic society
      (the San Francisco Dermatological Society), to which 142 (85%) replied. RESULTS:
      Two thirds of the respondents recalled BCC patients for screening examinations;
      of these, 58% followed up non-responders. Recall efforts were hampered by
      inefficient, unwieldy, and time-consuming techniques. CONCLUSION: Practicing
      dermatologists are motivated to recall BCC patients for examination, but
      guidelines and techniques for effective and efficient computerized recalling of
      skin cancer patients are needed. It is suggested that the American Academy of
      Dermatology set up a task force to develop guidelines and criteria for effective
      recall software.

PMID- 8151032
TI  - Use of nitrous oxide in hair transplantation surgery.
AB  - A study of 400 hair transplants carried out in 200 patients using nitrous oxide
      as an inducing agent before instillation of lidocaine 1%/epinephrine 100,000
      parts anesthesia is presented. Clinical efficacy, side effect profile, and
      toxicity profile are presented. Nitrous oxide is an excellent agent used for the
      preanesthetic induction phase of hair transplantation surgery.

PMID- 8151033
TI  - Buffered local anesthetics and epinephrine degradation.
AB  - Lidocaine with epinephrine is currently the most common local anesthetic agent
      used for facial soft tissue surgery. This combination is generally safe and
      effective in providing complete anesthesia and adequate hemostasis. Because
      epinephrine is unstable at physiologic pH, the commercial preparation is
      formulated with a low pH (3.5-5.5). Unfortunately, this acidic pH causes
      significant pain during infiltration. To reduce pain, clinicians sometimes buffer
      acidic local anesthetic agents with sodium bicarbonate. However, little is known
      about the stability of epinephrine when the pH of epinephrine is clinically
      altered. Using high pressure liquid chromatography (HPLC), epinephrine levels
      were measured after the addition of sodium bicarbonate. Our results indicate a
      significant amount of epinephrine degradation occurs in some of these specimens.
      Recommendations regarding the use of buffered local anesthetic agents are made.

PMID- 8151034
TI  - Spindle cell hemangioendothelioma. Report of three cases and review of the
      literature.
AB  - BACKGROUND: Spindle cell hemangioendothelioma lesions are uncommon, affect a wide
      age range in both sexes, and show a predilection for skin and subcutaneous tissue
      of the extremities. OBJECTIVE: To present three cases of spindle cell
      hemangioendothelioma and review the literature. METHODS: Three cases of spindle
      cell hemangioendothelioma are presented. RESULTS: Two of our cases first
      presented very early in life and progressed by local recurrences over many years.
      None of our cases showed evidence of metastases, but the lesions exhibited local
      aggressive and invasive behavior. Histologically, the lesions consist of
      alternating areas of dilated, thin walled cavernous vascular spaces and solid
      areas composed predominantly of spindle cells and clusters of epithelioid
      endothelial cells with intracytoplasmic vacuoles. That spindle cell
      hemangioendothelioma is a non-neoplastic lesion and not a neoplasm of borderline
      malignancy is suggested by the following observations from our cases: the
      repeated presence of organized intravascular thrombi in all cases, the early
      clinical presentation in two cases, and the presence of some degree of vascular
      malformation at the periphery of lesions. CONCLUSION: Both clinicians and
      pathologists should be aware of the existence of this lesion in order to diagnose
      and treat an affected patient correctly.

PMID- 8151035
TI  - Combining flaps. Medical canthal/lateral nasal root reconstruction utilizing
      glabellar "fan" and cheek rotation flaps--an O-to-Z variation.
AB  - An increased use of multiple flaps applied to single reconstructive problems is
      encouraged. Removal of a basal cell carcinoma involving the medial canthus and
      adjacent lateral nasal root skin resulted in significant defect. When a glabellar
      "fan" flap failed to provide adequate tissue for canthal reconstruction without
      undue distortion, a preplanned medial cheek rotation flap followed sequentially
      in the repair process. The basic principles of an O-to-Z flap reconstruction were
      therefore fulfilled by conjoining two different flap design applications.

PMID- 8151036
TI  - Application of electrosurgery in scalp reduction. Experience with an ultrasharp
      tungsten needle electrode.
AB  - An ultrasharp tungsten electrode was used in several hundred scalp reduction
      procedures from 1988-1992 at Peterson Medical Institute, Santa Monica,
      California. This unique instrument has proved to be a useful adjunct in
      facilitating hair restoration surgery.

PMID- 8151037
TI  - A communication from the Hellenic (Greek) Society for Dermatologic Surgery.

PMID- 8151039
TI  - Billing practices for micro- and minigrafting.

PMID- 8151038
TI  - Age and patient selection in planning hair transplantation procedures.

PMID- 8151040
TI  - Clinical misdiagnosis of melanoma as well as squamous cell carcinoma masquerading
      as seborrheic keratosis.

PMID- 8151041
TI  - Cutaneous ischemia caused by local anesthesia containing a vasoconstrictor in a
      patient with meralgia paresthetica.

PMID- 8151042
TI  - Further experiences using EMLA.

PMID- 8151043
TI  - Graft repair using methacrylate adhesive.

PMID- 8151044
TI  - Reducing fire risks of the flashlamp pumped 585-nm pulse dye laser.

PMID- 8151045
TI  - Sex and depression in the National Comorbidity Survey. II: Cohort effects.
AB  - Data from a nationally representative sample of the general population are used
      to study cohort differences in the prevalence of DSM-III-R Major Depressive
      Episode (MDE). We document increasing lifetime prevalence of MDE among both men
      and women in more recent cohorts, but no major change in the sex ratio over the
      40-year period retrospectively covered in the survey. We find a cohort difference
      in 12-month MDE, with older women much more likely than older men to have
      recurrent episodes. This sex difference in recurrence plays an important part in
      the elevated 12-month prevalence of depression among women compared to men in the
      45-54 age range.

PMID- 8151046
TI  - Short-term effects of electroconvulsive treatment on the uptake of 99mTc
      exametazime into brain in major depression shown with single photon emission
      tomography.
AB  - Fifteen patients with major depression who were being treated with bilateral
      electroconvulsive treatment (ECT) were investigated before and 45 min after a
      single ECT using split-dose Single Photon Emission Tomography (SPET or SPECT)
      with 99mTc-Exametazime. All patients suffered from unipolar depressive illness
      and were rated on the Newcastle scale and with the 17-item Hamilton scale. They
      completed tests of orientation and verbal memory on the day of ECT. For
      comparison, verbal memory was also tested on the preceding day. The uptake of
      99mTc-Exametazime was expressed relative to calcarine/occipital cortex.
      Significant decreases in tracer uptake were confined to the inferior anterior
      cingulate cortex. The changes were correlated with the severity of depressive
      symptoms and more weakly with decrements of memory function produced by ECT;
      there was no significant correlation with stimulus intensity or
      electroencephalographic measures of seizure duration.

PMID- 8151047
TI  - Temperament predicts clomipramine and desipramine response in major depression.
AB  - Clinical predictors of drug response in major depression have been weak and
      inconsistent. Eighty-four patients suffering from a current major depressive
      episode completed a 6-week double-blind trial of either clomipramine or
      desipramine. Temperament, as measured by the Tridimensional Personality
      Questionnaire, accounted for 35% of the variance in treatment outcome, compared
      with less than 5% predicted by clinical variables. In the more severely depressed
      patients, temperament predicted nearly 50% of the variance in treatment outcome,
      which is the first time that such a substantial predictor of drug response has
      been identified. Within depressed women, temperament also predicted response to
      different antidepressant drugs. The potential importance of temperament, and the
      need for replication of these findings is discussed.

PMID- 8151048
TI  - Effects of morning light treatment on subjective sleepiness and mood in winter
      depression.
AB  - The effects of morning light treatment on mood, subjective sleepiness and body
      temperature were investigated with 13 outpatients with winter depression and 13
      healthy controls. Bright light for 1 h daily for 2 weeks resulted in a
      significant reduction in depression ratings and evening subjective sleepiness in
      the patients compared with the healthy controls. Even a short 15-min exposure to
      light daily produced these changes.

PMID- 8151049
TI  - Predictors of response to alprazolam and placebo in patients with panic disorder.
AB  - Date from a panic disorder treatment study with 506 patients, comparing
      alprazolam and placebo in a double-blind manner for 8 weeks, were analyzed to
      identify demographic and clinical characteristics of the patients that might
      predict response to treatment. The strongest predictors of response to alprazolam
      were age over 40, and lower baseline levels of anxiety and phobic symptoms.
      Predictors of response to placebo were weaker and, in addition to lower levels
      anxiety and panic attacks, included a lack of previous psychiatric treatment.

PMID- 8151050
TI  - Direction of weight change in depression.
AB  - Direction of weight change in depression has recently been reported to be
      mediated by Body Mass Index (BMI). The present study examined the relation
      between direction of weight change in unipolar depression, BMI, and clinical
      variables such as severity of depression, melancholia, chronicity and recurrence
      in 89 patients with major depression. While the BMIs of individuals who gained
      weight when depressed were significantly higher than individuals with no weight
      change, the BMIs of individuals who lost weight were not significantly lower than
      those with no weight change. Direction of weight change was not predicted by
      severity of depression, melancholia, chronicity or recurrence. Concerns regarding
      conceptual and methodological difficulties in research on predictors of direction
      of weight change in depression are discussed.

PMID- 8151051
TI  - The classification of facial emotions: a computer-based taxonomic approach.
AB  - This study investigated whether the six 'fundamental' expressions of emotion each
      have configurational properties which would result in their being grouped into
      classes by a classification program. Twenty-three actors posed the six
      'fundamental' emotions of happiness, surprise, fear, disgust, anger, sadness and
      a neutral expression. Still images of these videotaped expressions were digitised
      and distance measures between facial landmark points were obtained. These
      measures were subjected to a numerical taxonomy procedure which generated five
      classes. Class 1 contained almost 70% of the happiness expressions. In Class 2
      the majority of expressions were of surprise. Each of classes three, four and
      five consisted of mixtures of emotions. Class 5 however, was distinguished from
      all other classes by the complete absence of happiness expressions. The typical
      facial appearance of members of each class is described (based on distance
      measures). These findings support the salience of happiness among emotional
      expressions and may have implications for our understanding of the brain's
      function in the early development of the human infant as a social organism.

PMID- 8151052
TI  - OSHA--authority over reason.

PMID- 8151053
TI  - Updating TMJ diagnostic concepts.

PMID- 8151054
TI  - Motivating patients to accept needed treatment now!

PMID- 8151055
TI  - Candidate for President-elect of the American Dental Association: an interview
      with Heber Simmons. Interview by John H. Mosteller.

PMID- 8151056
TI  - Defining successful treatment of "temporomandibular disorders".

PMID- 8151057
TI  - Detection of mosquito saliva-specific IgE and IgG4 antibodies by immunoblotting.
AB  - IgE and IgG subclass antibodies against Aedes communis mosquito saliva were
      studied by immunoblotting in 12 adults with immediate and/or delayed skin
      reactions to mosquito bites. Four antigenic proteins, with molecular weights of
      22, 30, 36, and 64 kd, were found in the mosquito saliva. Almost all subjects (11
      of 12) had anti-mosquito saliva-specific IgE antibodies directed against the 36
      kd protein. The IgG antibody response appeared to be restricted mostly to IgG4
      (11 of 12) and IgG1 (8 of 11) subclasses against the same 36 kd antigen. Ten of
      the 12 subjects had both IgE and IgG4 antibodies to the 36 kd protein. No anti
      mosquito antibodies were found in pooled sera of five infants never exposed to
      mosquito bites. These results show that most persons with immediate skin
      reactivity to A. communis mosquito bites have both IgE and IgG4 antibodies that
      recognize the 36 kd antigen present in the mosquito saliva, suggesting that anti
      saliva antibodies may play a role in the pathogenesis of mosquito bite reactions.

PMID- 8151058
TI  - Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects
      from a double-blind placebo study.
AB  - Twenty-eight patients (14 in an active treatment group and 14 in a placebo group)
      with rhinoconjunctivitis and asthma caused by cat hypersensitivity took part in a
      placebo-controlled, randomized, double-blind study to evaluate the risk-benefit
      quotient of the maintenance dose corresponding to 13.2 micrograms Fel d I
      antigen. The cat extract was biologically standardized and quantified with
      monoclonal antibodies (100 biological units: 33 microgram of Fel d I antigen, 650
      micrograms of albumin, and 99 micrograms of Fel d Bd/K30 antigen). After 1 year
      of treatment, the systemic reactions to cat extract immunotherapy were mild and
      infrequent. Improvement was observed in the active treatment group in comparison
      with the placebo group in the medication-symptoms score (p < 0.001); in skin
      prick test (p < 0.001), conjunctival provocation test (p < 0.001), and allergen
      bronchoprovocation test (p < 0.05) results, and in nonspecific bronchial
      hyperreactivity measured with methacholine, which was not statistically
      significant. This study demonstrates the favorable risk-benefit quotient of the
      dose of 13.2 micrograms of Fel d I antigen, which may serve as a future reference
      in defining the optimum dose and appropriate proportion of antigens that should
      be administered in cat extract immunotherapy.

PMID- 8151059
TI  - Nasal polyps: effects of seasonal allergen exposure.
AB  - Nasal polyps are characterized by chronic eosinophilic inflammation and often
      coexist with rhinitis and asthma. Many patients with polyps have no detectable
      allergy, and it is considered that allergy, at least in many cases, is not
      relevant to polyp to pathogenesis. To explore the association of nasal polyps
      with allergy, 16 patients with polyps and ragweed allergy (PRW +) and 16 patients
      with polyps who were not allergic to ragweed (PRW-) were compared with patients
      without polyps, 16 who were allergic to ragweed (NPRW +) and 16 who were not
      allergic to ragweed (NPRW-), before and during the ragweed season. The level of
      ragweed allergy was comparable in the PRW+ and NPRW+ populations as determined by
      ragweed skin test wheal diameter, ragweed IgE RAST percent binding, and total
      serum IgE. Symptom scores before the ragweed season recorded on visual analog
      scales for the symptoms of blockage, sneezing, decreased smell, itch, postnatal
      drip, and runny nose were high in patients in the PRW+ and PRW- groups and did
      not change during ragweed season. Mean symptom scores were low in the NPRW+ group
      before ragweed season and increased during the season to levels similar to those
      of patients in the PRW+ and PRW- groups. Preseason nasal lavage albumin
      concentration was higher in subjects with polyps than those without polyps (58.5,
      98) versus (13.6, 15 micrograms/ml) (p = 0.02) and did not change significantly
      in any group with seasonal exposure. Data are presented as mean, 1 SD;
      comparisons are made with unpaired t tests.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151060
TI  - Follow-up of asthma from childhood to adulthood: influence of potential childhood
      risk factors on the outcome of pulmonary function and bronchial responsiveness in
      adulthood.
AB  - The outcome of asthma in 406 children, aged 8 to 12 years, was studied. Follow-up
      in adulthood was 86%, with a mean age of 24.7 years and a mean interval of follow
      up of 14.8 years. The predictive value of gender and various childhood variables
      on the adult level of pulmonary function (forced expiratory volume in 1 second
      [FEV1]) and bronchial responsiveness in adulthood was assessed. An increase in
      mean percent predicted FEV1 from childhood to adulthood was found, both in
      subjects with (76%) and without (24%) current respiratory symptoms. The only
      childhood variable predictive of adult level of FEV1 was the level of percent
      predicted FEV1 (p < 0.01). The proportion of subjects with a histamine
      provocative concentration causing a 10% decrease in FEV1 less than or equal to 16
      mg/ml decreased significantly in adulthood. The degree of bronchial
      responsiveness had increased slightly in adults with symptoms (p = 0.87), whereas
      it had decreased significantly in subjects without symptoms (p < 0.01). Female
      subjects were significantly more responsive in adulthood than male subjects (p =
      0.047). The childhood degree of bronchial responsiveness significantly predicted
      the presence of bronchial responsiveness in adulthood (p = 0.02). We conclude
      that childhood percent predicted FEV1 is relevant to predict the outcome of the
      adult pulmonary function level, whereas female gender and the childhood degree of
      bronchial responsiveness are important for the prediction of adult degree of
      bronchial responsiveness among children with asthma.

PMID- 8151061
TI  - Effect of antigen on the glycoconjugate profile of tracheal secretions and the
      epithelial glycocalyx in allergic sheep.
AB  - To characterize the glycoconjugate composition of tracheal secretions and the
      apical glycocalyx of the tracheal epithelium under baseline conditions and after
      antigen challenge, sheep allergic to Ascaris suum were intubated with a double
      balloon nasotracheal tube to create a tracheal chamber. After an initial tracheal
      lavage, the animals were either exposed to intratracheally nebulized phosphate
      buffered saline (PBS) (3 ml, n = 6) or A. suum antigen (251,000 protein nitrogen
      units in 3 ml of PBS, n = 6). Tracheal lavage was repeated 2 hours later, and the
      animals were killed. An enzyme-linked lectin assay and lectin histochemical
      analysis were used to characterize carbohydrate residues in lyophilized,
      resuspended tracheal secretions and the apical glycocalyx of the tracheal
      epithelium, respectively. Eight lectins were used to detect GalNAc, alpha-Gal,
      beta-Gal, alpha-Fuc (1-3)Man, alpha-Man/Glu, alpha-Man, and alpha-(2-3)sialyl
      residues. The amounts of total nondialyzable solids, proteins, and lipids in
      tracheal secretions were approximately twice as high after exposure to A. suum
      than after exposure to PBS. All carbohydrate residues were present in tracheal
      secretions after exposure to PBS and A. suum, but the reactivity was higher after
      exposure to A. suum for beta-Gal (+125%), alpha-Man/Glu (+150%), alpha-(1-3)Man
      (+287%), alpha-(2-3)sialyl (+353%), and alpha-Man (+448%) (p < 0.05). Likewise,
      the apical glycocalyx contained all carbohydrate residues after exposure to PBS
      and A. suum; afer exposure to A. suum, the reactivity was greater for alpha
      GalNAc (+18%), alpha-(2-3)sialyl (+90%), beta-Gal(1-3)GalNAc (+433%), and alpha
      (1-3)Man (+482%) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151062
TI  - Histamine-induced venodilation in human beings involves both H1 and H2 receptor
      subtypes.
AB  - Histamine is a potent vasodilatory substance released during anaphylaxis. The
      purpose of this study was to investigate the mechanism by which histamine
      produces venodilation in humans in vivo with the use of the dorsal hand-vein
      compliance technique. In healthy volunteers full dose-response curves were
      constructed by infusing histamine, before and after administration of an H1 or H2
      antagonist or both antagonists, into dorsal hand veins preconstricted with the
      alpha-adrenergic agonist phenylephrine. In the presence of the H1 antagonist
      brompheniramine (530 ng/min), the maximal venodilatory response to histamine
      decreased from 128% +/- 57% to 78% +/- 15% (p < 0.05). In the presence of H2
      antagonist cimetidine (49 micrograms/min), the maximal venodilatory response to
      histamine decreased from 120% +/- 33% to 48% +/- 26% (p < 0.01). Concurrent
      infusion of histamine with the combination of cimetidine and diphenhydramine
      resulted in almost complete abolishment of histamine-induced venodilation.
      Methylene blue (6.8 micrograms/min), an inhibitor of the action of endothelium
      derived relaxing factor, decreased the vasodilatory response to histamine from
      131% +/- 23% to 73% +/- 24% (p = 0.01). The results suggest that the venodilatory
      response of histamine is mediated through both H1 and H2 receptor subtypes and
      that this response is mediated in part by endothelium-derived relaxing factor.

PMID- 8151063
TI  - Lymphocyte infiltration and thickness of the nasal mucous membrane in perennial
      and seasonal allergic rhinitis.
AB  - We have used immunocytochemical techniques to study infiltration by lymphocytes
      in biopsy specimens of the nasal mucosal membrane in 24 atopic patients and 10
      normal volunteers. Twelve patients had perennial rhinitis and 12 had seasonal
      allergic rhinitis (SR) to grass pollen. Biopsy specimens were taken both in and
      out of the pollen season in patients with SR. Biopsy specimens were strained with
      the indirect immunoperoxidase technique and monoclonal antibodies to CD3, CD4,
      CD8, CD22, and CD25. T helper cells (CD4+) and CD24+ cells were significantly
      more numerous in patients exposed to allergen (those with perennial rhinitis and
      SR in season) compared with normal volunteers, whereas values for SR out of
      season were intermediate. The thickness of the nasal epithelium was significantly
      (p < 0.05) greater in biopsy specimens from patients with perennial rhinitis
      (mean, 51.43 microns) than in those from patients with SR in season (median,
      32.44 microns). These results suggest that in allergic rhinitis, natural exposure
      to allergen is accompanied by increased infiltration of the nasal mucous membrane
      by T-helper and CD25+ cells.

PMID- 8151064
TI  - Affinity purification of latex antigens.
AB  - Latex extracts are complex mixtures of antigenic peptides. We attempted to raise
      monoclonal antibodies to latex and to use these antibodies to purify latex
      antigens. A monoclonal antibody, CRI-C, was raised by standard techniques.
      Peptides of nonammoniated latex (NAL) and ammoniated latex were
      electrophoretically separated and transferred for immunoblots. CRI-C was
      covalently attached to an agarose column. NAL was passed over the column, and
      purified antigen was then eluted. The eluate was analyzed by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis and RAST inhibition with sera
      from health care workers and children with spina bifida. CRI-C recognized a
      single band in ammoniated latex immunoblots and several distinct bands in NAL.
      The affinity-purified antigen of CRI-C (C-Ag) had multiple bands of less than 20
      kd and was 3.9 times more potent in RAST inhibition than NAL when sera from
      patients with spina bifida were used. However, when health care workers' sera
      were used, there was no significant difference in the inhibitory potency of NAL
      and C-Ag. CRI-C appears to recognize a distinct and important epitope in the IgE
      immune response to latex of patients with spina bifida.

PMID- 8151065
TI  - Granulocyte-macrophage colony-stimulating factor stimulates macrophages to
      respond to IgE via the low affinity IgE receptor (CD23).
AB  - We have found increased concentrations of granulocyte-macrophage colony
      stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid of 11 patients
      with nocturnal asthma (15.3 +/- 4.6 pg/ml) compared with normal subjects (2.3 +/-
      6.1 pg/ml) (p = 0.03). In contrast to patients with asthma, low affinity IgE
      receptors (Fc epsilon RII or CD23) are not expressed on monocytes obtained from
      healthy, nonatopic donors. Fc epsilon RII expression was induced by the cytokines
      GM-CSF and interleukin (IL)-4 either alone or in combination. As assessed by flow
      cytometry, the combination of IL-4 and GM-CSF was found to be synergistic,
      inducing up to 54.8% +/- 4.6% Fc epsilon RII-positive monocytes compared with a
      maximum of 27.4% +/- 5.0% and 30.0% +/- 4.0% with IL-4 and GM-CSF alone,
      respectively (p < 0.05 compared with either cytokine alone). Human monocytes from
      the peripheral blood of seven normal subjects were cultured for 24 hours with and
      without IL-4 or GM-CSF. With IL-4, addition of IgE/anti-IgE complexes failed to
      induce IL-1 secretion and inhibited IL-1 secretion induced by
      lipopolysaccharides. The addition of GM-CSF or IgE immune complexes alone
      resulted in no additional IL-1 secretion in supernatants of the untreated
      monocytes, whereas the IgE complexes did stimulate IL-1 secretion by monocytes
      cultured in GM-CSF, as measured by ELISA (from 0.7 +/- 0.2 ng/ml to 2.3 +/- 0.5
      ng/ml; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151066
TI  - Immunosuppression in the treatment of disease.

PMID- 8151067
TI  - Deconvolutions based on singular value decomposition and the pseudoinverse: a
      guide for beginners.
AB  - Singular value decomposition (SVD) is deeply rooted in the theory of linear
      algebra, and because of this is not readily understood by a large group of
      researchers who could profit from its application. In this paper, we discuss the
      subject on a level that should be understandable to scientists who are not well
      versed in linear algebra. However, because it is necessary that certain key
      concepts in linear algebra be appreciated in order to comprehend what is
      accomplished by SVD, we present the section, 'Bare basics of linear algebra'.
      This is followed by a discussion of the theory of SVD. Next we present step-by
      step examples to illustrate how SVD is applied to deconvolute a titration
      involving a mixture of three pH indicators. One noiseless case is presented as
      well as two cases where either a fixed or varying noise level is present.
      Finally, we discuss additional deconvolutions of mixed spectra based on the use
      of the pseudoinverse.

PMID- 8151068
TI  - A continuous spectrophotometric assay for alkaline phosphatase with
      glycerophosphate as substrate.
AB  - We describe a continuous coupled spectrophotometric assay for alkaline
      phosphatase which uses alpha- or beta-glycerophosphate as substrate, and glycerol
      dehydrogenase as ancillary enzyme. The glycerol liberated by alkaline phosphatase
      is determined by measuring the increase in absorbance at 340 nm caused by NADH
      formation that is combined with glycerol oxidation by the ancillary enzyme. The
      assay procedure was optimized using a bovine bone extract as alkaline phosphatase
      source.

PMID- 8151069
TI  - Properties and applications of a new type of iodinated gradient medium.
AB  - This paper reports on the properties of a new iodinated density-gradient medium,
      Iotrolan, and its potential application for separating dense cells. Iotrolan is a
      dimeric, nonionic, iodinated compound which is distinguished by its ability to
      form dense, non-viscous gradients of low osmolarity. Isotonic gradients of up to
      1.30 g/ml can be formed, allowing even dense cells such as sperm to be separated
      under isotonic conditions.

PMID- 8151070
TI  - Fluorometric determination of the kinetics of anthracyclines uptake by cells.
AB  - Fluorometric measurements on extracellular medium are shown to allow kinetic
      parameters of in vitro anthracycline uptake by cells to be calculated. The method
      provides influx and efflux rates, as well as the time dependence of both influx
      and efflux. It is applied to a normal thyroid epithelial cell line (FRTL-5) and a
      cell line (MPTK-6) derived from the lung metastases of a thyroid carcinoma
      exposed to daunorubicin at concentrations within the range of 250 to 1000 ng/ml.
      The results show that the number of cells influences the dependence of the
      kinetics upon the extracellular drug concentration and that the MPTK-6 cells are
      endowed with very efficient efflux mechanisms.

PMID- 8151071
TI  - A fluorometric assay of peroxidase activity utilizing 2',7'-dichlorofluorescein
      with thiocyanate: application to the study of salivary secretion.
AB  - A sensitive assay for secretory peroxidase activity has been developed utilizing
      the fluorogenic substrate 2',7'-dichlorofluorescein in the presence of
      thiocyanate. The assay has been characterized using bovine lactoperoxidase and
      used to determine the peroxidase activities of salivas and extracts obtained from
      rat submandibular glands. Comparison of the 2',7'-dichlorofluorescein-thiocyanate
      assay and the commonly used 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic
      acid) colorimetric assay indicates that the new assay is approx. 50-fold more
      sensitive. This has enabled measurement of peroxidase activities present in
      parasympathetic saliva samples which were beyond the detection limit of the
      colorimetric assay. Despite great differences in the peroxidase activities and
      protein concentrations of parasympathetic and sympathetic salivas and tissue
      extracts, the activities per unit protein were very similar. Unlike most other
      published methods, prior dialysis of samples to remove interference by endogenous
      thiocyanate is not required. The assay is therefore convenient and will be
      particularly useful for applications in which sample volume or peroxidase
      activity is low.

PMID- 8151072
TI  - Mitochondria in evolution and disease.

PMID- 8151073
TI  - Infantile spasms secondary to the surgical excision of a brain tumor.

PMID- 8151074
TI  - Human parvovirus B19 antibodies in infantile autism.

PMID- 8151075
TI  - Pediatric syringomyelia.
AB  - Syringomyelia was first recognized as a disease process some 400 years ago. The
      process of cystic dilation of the spinal cord is unpredictable and may result in
      a delay of many decades before the symptoms and signs of neurologic and
      orthopedic changes become apparent and commensurate with the observed cystic
      changes within the spinal cord. The syringomyelic process is usually associated
      with trauma, tumor, or congenital abnormalities at the craniocervical junction or
      along the spinal neuraxis. Several theories have been proposed as to processes
      involved in the development of spinal cyst formation, although none are
      completely compatible with the observed clinical pathology of syrinx development.
      Magnetic resonance imaging has markedly improved our ability to study the anatomy
      and natural history of syrinx formation, but to date, our understanding of the
      process remains imprecise. In view of the limited understanding of the
      pathophysiology of this disease process, it is not surprising that a variety of
      treatment regimens have been proposed and their efficacy remains difficult to
      fully evaluate.

PMID- 8151076
TI  - Elevated biopterin and homovanillic acid levels in cerebrospinal fluid from
      children with aseptic meningitis.
AB  - To examine biopterin fractions and biogenic amine metabolites in cerebrospinal
      fluid in aseptic meningitis, the concentrations of homovanillic acid, 5
      hydroxyindoleacetic acid, and the total, the oxidized form, and the reduced form
      of biopterin were determined in cerebrospinal fluid specimens from 15 children
      with aseptic meningitis in the acute phase, 15 children with aseptic meningitis
      in the recovery phase, and six other children as controls. The concentration of
      each substance was significantly higher in the acute phase than in the recovery
      phase. Homovanillic acid in the acute phase was significantly increased compared
      to that in the control group. The concentrations of the total, the oxidized form,
      and the reduced form of biopterin, and 5-hydroxyindoleacetic acid were higher in
      the acute phase than those in the controls; however, the differences were not
      significant. The concentration of each substance in the recovery phase was not
      significantly different from that in the controls. There was no difference in the
      5-hydroxyindoleacetic acid/homovanillic acid ratio or in the reduced form/total
      biopterin ratio among the patients in acute and recovery phases and the controls.
      These results suggested that levels of biopterin and biogenic amine metabolites
      in cerebrospinal fluid are increased in the acute phase of aseptic meningitis and
      return to normal during the recovery phase. This is the first report of increased
      concentrations of biopterin fractions and biogenic amine metabolites in aseptic
      meningitis.

PMID- 8151077
TI  - Abnormal carbohydrate metabolism in cerebrospinal fluid in Rett syndrome.
AB  - We analyzed lactate, pyruvate, and citric acid cycle intermediates in
      cerebrospinal fluid by high-performance liquid chromatography in Rett syndrome
      patients (n = 27; mean age, 5.7 +/- 3.4 years) and age-matched female controls (n
      = 12; mean age, 7.0 +/- 3.3 years). The lactate, pyruvate, alpha-ketoglutarate,
      and malate were significantly elevated in Rett syndrome compared to the controls.
      The lactate/pyruvate ratio was not different. On the other hand, cerebrospinal
      fluid citrate, cis-aconitate, succinate, fumarate, and oxaloacetate were not
      significantly different in Rett syndrome patients than in the controls. We also
      evaluated the correlation between these acids and clinical symptoms and signs,
      including clinical stage, seizures medications (anticonvulsants or naltrexone),
      developmental quotient, self-abuse, and hyperventilation or apnea or both. The
      concentrations of all these acids did not differ significantly with clinical
      stage. Lactate elevation significantly correlated with apnea. Lactate and
      pyruvate elevation significantly correlated with hyperventilation or with both
      breathing abnormalities. Our observations in this sample of patients with Rett
      syndrome led us to speculate that patients with the Rett syndrome may have
      defective carbohydrate metabolism. Elevated mitochondrial reduced nicotinamide
      adenine dinucleotide-linked substrates suggest that reduced nicotinamide-adenine
      dinucleotide-ubiquinone oxidoreductase may be deficient in the brain in Rett
      syndrome patients.

PMID- 8151078
TI  - Valproate-associated acute pancreatitis in a child with neuronal ceroid
      lipofuscinosis.
AB  - An 11-year-old girl with juvenile neuronal ceroid lipofuscinosis developed acute
      pancreatitis secondary to valproic acid treatment, which resolved after
      discontinuation of the medication and conservative treatment. To my knowledge,
      this is the first reported case of neuronal ceroid lipofuscinosis with valproate
      associated pancreatitis. Children with neuronal ceroid lipofuscinosis may be
      susceptible to developing this complication.

PMID- 8151079
TI  - Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes
      (MELAS): current concepts.
AB  - Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS)
      syndrome is one of many mitochondrially inherited multisystem diseases. The
      features of 110 reported mitochondrial encephalomyopathy, lactic acidosis, and
      strokelike episodes patients are reviewed to define the clinical spectrum of this
      disease. The clinical disorder, in addition to emerging concepts of genetic
      etiology, is promoting our understanding of mitochondrial functions. New
      knowledge may lead to more rational therapies. Finally, the recent revolution in
      the study of mitochondrial diseases may further our understanding of other
      degenerative disorders and even aging.

PMID- 8151080
TI  - Ipsilateral constructional apraxia.
AB  - Two boys, aged 7 and 12 years, with nondominant (right) hemispheric acquired
      vascular lesions and left visual-field disturbances had right spatial
      constructional disabilities, contralateral to that which would be expected. These
      unusual disturbances may represent the previously unreported phenomena of
      ipsilateral neglect or ipsilateral constructional apraxia.

PMID- 8151081
TI  - Paroxysmal kinesigenic dystonia after methylphenidate administration.
AB  - We report a patient who developed paroxysmal kinesigenic dystonia shortly after
      initiation of therapy with methylphenidate for presumed attention deficit
      hyperactivity disorder. Attacks persisted long after methylphenidate was
      discontinued and responded completely to treatment with carbamazepine. Though it
      is possible that methylphenidate caused this syndrome in our patient, it is more
      likely that the stimulant triggered the onset of a genetically determined
      disorder.

PMID- 8151082
TI  - Hypoplasia of the corpus callosum: a study of 445 consecutive MRI scans.
AB  - The size of the corpus callosum was assessed visually and by computer-assisted
      image analysis in a series of 445 consecutive magnetic resonance imaging (MRI)
      scans in children under 17 years of age. Fifty individuals were subjectively
      identified with small corpora callosa on visual inspection of the MRI scans.
      Seven patients had true hypoplasia of the corpus callosum after comparing the
      computer-measured relative size of the structure to previously established normal
      values. Five additional patients had complete agenesis, and two had partial
      agenesis of the corpus callosum. The cognitive functional levels of the seven
      patients with callosal hypoplasia and a control group of 63 randomly selected
      individuals from the remainder of the group were ascertained by record review.
      Seventy-one percent of the patients with hypoplasia of the corpus callosum and
      29% of the control group had impaired function. The P value determined by
      Fisher's exact test was P = .061, suggesting that further study with greater
      numbers may be warranted. The prevalence of mental retardation in this condition,
      and the fact that hypoplasia is as common as complete and partial agenesis of the
      corpus callosum combined, suggest that hypoplasia of the corpus callosum is a
      marker of cerebral dysgenesis that should be looked for in the appropriate
      clinical setting.

PMID- 8151083
TI  - Pseudo-tics in Tourette syndrome.
AB  - We describe two patients with Tourette syndrome who also had pseudo-tics. The
      psychogenic movements resolved in both children when the stressful issues in
      their lives were addressed. It is important to differentiate psychogenic symptoms
      from tics and compulsions in children with Tourette syndrome in order to avoid
      unnecessary medication and allow appropriate therapy.

PMID- 8151084
TI  - Leigh syndrome: pyruvate dehydrogenase defect. A case with peripheral neuropathy.
AB  - Pyruvate dehydrogenase deficiency is one of the most common causes of
      encephalopathy associated with lactic acidosis and is known to account for
      congenital lactic acidosis, recurrent ataxia, and infantile Leigh syndrome.
      Hitherto, however, peripheral neuropathy has not been regarded as a presenting
      symptom of pyruvate dehydrogenase deficiency. Here, we report on a boy who
      presented peripheral neuropathy with severe limb hypotonia, absent deep-tendon
      reflexes, and reduced motor nerve conduction velocities at 8 months of age.
      Persistent hyperpyruvicemia with normal lactate/pyruvate molar ratios in plasma
      were highly suggestive of a pyruvate dehydrogenase deficiency, and the
      determination of pyruvate dehydrogenase activity in circulating lymphocytes led
      to the diagnosis of pyruvate decarboxylase (PDH-E1) deficiency in the proband.
      Based on this observation, we suggest that pyruvate dehydrogenase deficiency
      should be considered in the diagnosis of peripheral neuropathy in infancy,
      especially when associated with persistent hyperpyruvicemia, normal
      lactate/pyruvate molar ratios in plasma, and recurrent episodes of drowsiness and
      hypotonia of unknown origin.

PMID- 8151085
TI  - Disseminated multifocal herpes zoster leukoencephalitis and subcortical
      hemorrhage in an immunosuppressed child.
AB  - We describe a rare case of multifocal varicella-zoster leukoencephalitis in an
      immunosuppressed adolescent boy who developed a herpetiform rash on his groin and
      subsequently presented with a subacute encephalopathy, aphasia, and hemiparesis.
      Magnetic resonance imaging scan of the brain revealed multifocal bi-hemispheric
      target-like lesions predominantly in the white matter. A magnetic resonance
      imaging scan 2 weeks later showed a subcortical hemorrhage in the left insular
      region. He received long-term high-dose intravenous acyclovir and had significant
      improvement in his neurologic status.

PMID- 8151086
TI  - Magnetic resonance imaging of postmortem infant brains.
AB  - In order to obtain postmortem magnetic resonance images of infant brains, the
      formalin-fixed brains of 37 infants, ranging in age from 17 days to 17 months,
      were studied. Factors that improved scan resolution included formalin fixation,
      not washing the formalin from the brain, imaging the brain with a thin film of
      water over it, and the use of an extremity coil. The scan resolution was of
      sufficient quality to direct the histopathologist to regions requiring
      microscopic examination and to map the progress of myelination.

PMID- 8151087
TI  - Head circumferences standards in neonates.
AB  - Head circumference at birth is an important measure of intrauterine growth,
      reflecting accurately brain growth and predicting subsequent development.
      Standards need to reflect the population and the factors that affect intrauterine
      growth in the population and must be constructed in a manner that is clinically
      useful and predictive. Many of the present standards used to assess newborn
      infants are inadequate because of the limitations of sample size and study
      design. As a result, the current standards are not adequate for premature infants
      below 30 weeks of gestation and, in newborns from later in gestation, may
      underreport significant deviations from the mean in certain situations.

PMID- 8151088
TI  - Kluver-Bucy syndrome in juvenile neuronal ceroid lipofuscinosis.
AB  - Although Kluver-Bucy syndrome in adults is commonly associated with
      neurodegenerative conditions, Kluver-Bucy syndrome in children has been
      recognized almost exclusively in association with acute bitemporal injury or
      dysfunction. We report a child with juvenile neuronal ceroid lipofuscinosis, who
      developed dementia, childhood-onset autistic disorder, and Kluver-Bucy syndrome.
      The behavioral features of this case are compared with those of previously
      reported cases of juvenile neuronal ceroid lipofuscinosis and with previous
      reports of Kluver-Bucy syndrome in children and adults.

PMID- 8151089
TI  - Neuroaxonal dystrophy at birth with hypertonicity and basal ganglia
      mineralization.
AB  - A full-term male infant exhibited rigidity of all extremities with hyperreflexia
      beginning soon after birth and lasting until his death at age 6 months. Head
      circumference remained at the 25th to 50th percentile. Distinct sleep-wake cycles
      and responsiveness to visual, auditory, and tactile stimuli developed. Metabolic
      studies, skin biopsy, electroencephalography, and electromyography produced
      normal results. Head computed tomographic and magnetic resonance imaging scans
      revealed mineralization of the basal ganglia and thalamus. Muscle and nerve
      biopsy results were consistent with axonal dystrophy. Autopsy showed widespread
      neuronal loss, with reactive gliosis, marked in the globus pallidus and brainstem
      reticulate core; spheroids in globus pallidus, nucleus cuneatus, and upper
      cervical cord; and mineralized neurons in the inner division of globus pallidus
      and thalamus. Neonatal hypertonia, rapid progression, and mineralization of the
      basal ganglia are unusual features of neuroaxonal dystrophy exhibited in this
      case.

PMID- 8151090
TI  - Regional differences in the critical period neurodevelopment in the mouse:
      implications for neonatal seizures.
AB  - The voltage-sensitive calcium channel probe 125I-omega-GVIA conotoxin has been
      shown to be a developmental marker in whole brain preparations of Swiss Webster
      mice. The present study looks more carefully at regional dissections of the mouse
      brain (cerebrum, cerebellum, and brain stem) at postnatal day 8 and postnatal day
      16. 125I-omega-GVIA conotoxin binding, thought to be presynaptic, showed a
      dramatic increase between postnatal days 8 and 16 in the cerebral cortex, a
      decrease in the cerebellum, and no change in the brain stem. The dramatic
      cerebral cortex increases indicated by these binding data correspond to a
      critical period between postnatal day 11 and postnatal day 14 in Swiss Webster
      mice; during this critical period, dendrites exhibit rapid outgrowth, sensory
      modalities come on line, electroencephalographic patterns mature, and the cortex
      reaches adult proportions. This period parallels a similar initiation of
      electrical maturation in the 28- to 32-week neonatal human brain. We conclude
      from these data that the unusual clinical presentation of neonatal seizures is
      not just the result of immature myelin formation. It includes incomplete synapse
      formation linking the cortex to the brain stem.

PMID- 8151091
TI  - Dissociation between delayed alternation and memory after pediatric head injury:
      relationship to MRI findings.
AB  - This study investigated the usefulness of a delayed alternation task in
      characterizing the cognitive sequelae of closed head injury in children and
      adolescents. Verbal learning and memory (California Verbal Learning Test) were
      also studied for comparison. Sixty-two closed head injury patients (mean age, 9.6
      years), who were studied after an average postinjury interval of 20 months, were
      divided according to both their lowest postresuscitation Glasgow Coma Scale score
      (3 to 8 versus 9 to 15) and age range (5 to 7 years versus 8 to 16 years) at the
      time of testing. Magnetic resonance imaging was performed to evaluate the
      relationship of focal brain lesions to cognitive and memory performance. Fifty
      six neurologically normal children (mean age, 9.9 years) were tested on the same
      measures. The results disclosed no relationship between delayed alternation
      performance and severity of injury. In contrast, verbal memory was impaired in
      the severely-injured patients, relative to both controls and less severely
      injured patients. Frontal lobe (but not extrafrontal) lesion size incremented the
      Glasgow Coma Scale score in predicting verbal memory, but there was no
      relationship between focal brain lesions and delayed alternation performance. In
      contrast to the tendency for more efficient delayed alternation performance in
      the 5- to 7-year-old subjects than in the 8- to 16-year-old subjects, verbal
      memory significantly improved with age in the closed head injury and control
      groups. Notwithstanding our essentially negative findings for delayed
      alternation, it is possible that this task may be useful for assessing frontal
      lobe injury in younger children or infants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151092
TI  - A hypotonic infant with complete deficiencies of acid maltase and debrancher
      enzyme.
AB  - Infantile acid maltase deficiency is an autosomal recessive disease that
      invariably leads to death in the first 2 years of life. Debrancher deficiency,
      also an autosomal recessive disease, however, carriers a slowly progressive
      course. We report a hypotonic infant with a typical clinical course of infantile
      acid maltase deficiency in whom biochemical investigation revealed complete
      deficiencies of both acid maltase and debrancher enzyme.

PMID- 8151093
TI  - Migraine in the infant and toddler.
AB  - This report consists of 13 patients who on retrospective analysis had had
      periodic symptomatology in the first 2 years of life, and who on later evaluation
      were determined to have juvenile migraine. The commonest early expression
      consisted of vomiting, accompanied by behavioral change. Seven of 13 showed some
      indication of headache. Other symptoms such as sleep relief, pallor, and vertigo
      or ataxia were relatively common. A family history of migraine, primarily
      maternal, was found in 11 of 12 patients in whom it could be evaluated.

PMID- 8151094
TI  - Enhancement of unbound clearance of ICG by plasma proteins, demonstrated in human
      subjects and interpreted without assumption of facilitating structures.
AB  - The kinetics of hepatic removal of protein-bound substances were studied in nine
      human subjects with various liver diseases by the use of indocyanine green as a
      model substance. Intrinsic hepatic clearance of indocyanine green was measured by
      means of a constant infusion of indocyanine green and concentration measurements
      of indocyanine green in arterial and hepatic venous plasma samples. During the
      indocyanine green infusion, 1-1.51 of dextran-70 was given whereby a stable
      dilution of the plasma protein concentration by a factor of 0.6-0.8 was obtained.
      In each of the subjects, the intrinsic clearance of indocyanine green increased
      after the protein dilution (range 11-64%). Elimination of ethanol (not protein
      bound), similarly assessed, was not significantly changed. The traditional
      hypothesis that unbound clearance (intrinsic clearance divided by the free
      fraction of the ligand) is independent of protein concentration was refuted since
      in each of the subjects the protein dilution was followed by a reduction of the
      unbound clearance of ICG (P < 0.005, n = 9). We examined whether these
      observations imply some special mechanism (e.g. a hepatocyte protein receptor) by
      which the unbound clearance is enhanced by the binding protein(s). The previously
      developed pseudofacilitation model--describing the effects of ligand-protein
      diffusion and dissociation in an unstirred plasma layer near the hepatocyte--was
      extended to the case of a mixture of binding proteins, and parameter-free bounds
      were derived to predict the response of intrinsic clearance to protein dilution.
      The observed changes of the intrinsic clearance values did not violate these
      bounds (P < 0.002, n = 9). Thus no facilitating mechanisms are necessary to
      account for the observed deviations from the traditional hypothesis.

PMID- 8151095
TI  - Effects of vasopressin and nicardipine on hemodynamics and liver function in
      patients with cirrhosis: comparison with vasopressin alone.
AB  - The effects of a combination of vasopressin and a calcium channel blocker
      (nicardipine) on portohepatic hemodynamics and liver function were compared with
      the effects of vasopressin alone in 18 patients with portal hypertension. Nine
      patients received 0.4 units/min of vasopressin and 9 patients received the same
      dose of vasopressin plus 0.3 mg/min of nicardipine for 40 min. Vasopressin plus
      nicardipine induced a significant reduction in both free portal venous pressure
      and the portal venous pressure gradient. These effects were similar to the
      changes with vasopressin alone (-14% vs. -16% in free portal venous pressure; 
      29% vs. -31% in portal venous pressure gradient). Vasopressin decreased both
      hepatic blood flow (-34%, P < 0.01) and intrinsic clearance of indocyanine green
      (-22%, P < 0.05). In contrast, these two parameters did not significantly change
      after vasopressin plus nicardipine (-8% and -3%, respectively). These results
      suggest that the addition of nicardipine improves hepatic impairment induced by
      vasopressin but causes no further reduction on portal pressure.

PMID- 8151096
TI  - Effect of tauroursodeoxycholate on actin filament alteration induced by
      cholestatic agents. A study in isolated rat hepatocyte couplets.
AB  - The mechanism of the protective effect of ursodeoxycholic acid in cholestatic
      liver diseases remains unclear. Since there is evidence that alterations in the
      pericanalicular actin microfilament network play a major role in cholestasis, the
      aims of this study were (a) to determine the effect of the cholestatic agents,
      taurolithocholate (TLC) and erythromycin estolate (ERY), on F-actin distribution
      in isolated rat hepatocyte couplets and (b) to assess the effect of
      tauroursodeoxycholate (TUDC) and taurocholate on the modifications induced by
      these two compounds. F-actin was stained with fluorescein-isothiocyanate
      phalloidin and fluorimetric measurements were performed using a scanning laser
      cytometer ACAS 570. F-actin distribution was assessed in the couplets by the
      ratio of the pericanalicular area fluorescence/total couplet fluorescence
      (CF/TF). At non-cytotoxic concentrations, TLC (50, 100 microM) and ERY (10, 50,
      100 microM) induced a significant accumulation of F-actin around the bile
      canaliculus as indicated by increased fluorescence in the pericanalicular area
      and by the increased CF/TF ratio compared with the controls. Electron microscopy
      studies showed significant alterations in bile canaliculi microvilli in couplets
      treated with 100 microM TLC. Only a few canaliculi showed an increase in
      pericanalicular microfilaments after treatment with 100 microM ERY. As assessed
      by scanning laser cytometry, TUDC prevented changes in F-actin distribution when
      it was added to the medium with taurolithocholate or erythromycin estolate at
      equimolar concentrations. However, the morphological changes observed by electron
      microscopy after treatment with TLC were not modified by co-treatment with TUDC.
      Taurocholate was ineffective. We conclude that (a) abnormalities of
      pericanalicular F-actin microfilaments occur in two different models of
      cholestasis, (b) tauroursodeoxycholate prevents the accumulation of
      pericanalicular F-actin detected by scanning laser cytometry but not the
      morphological changes of the canaliculus observed by electronic microscopy.
      Therefore, in these experimental conditions, the protective effect of TUDC
      appears to be partial.

PMID- 8151097
TI  - Acute effects of partial hepatectomy on liver blood flow in the jaundiced rat.
AB  - The aim of this study was to define the effects of hepatic resection on liver
      blood flow and portal pressure in the presence of obstructive jaundice. Liver
      blood flow and portal pressure were measured in 17 jaundiced animals (5 days bile
      duct ligation) and 16 control animals. A 70% liver resection with or without
      hepatic artery ligation was performed in the control animals. On day 5, the
      animals underwent a second operation. Hepatic artery ligation alone was performed
      in a group of control animals. In jaundiced rats there was a decrease in liver
      blood flow (1.24 +/- 0.23 ml/min per g vs. normal 1.91 +/- 0.38 ml/min per g, P <
      0.01) and an increase in portal pressure (11.2 +/- 3.47 mmHg vs. normal 6.93 +/-
      1.01 mmHg, P < 0.01). After partial hepatectomy, a significant increase in liver
      blood flow was observed in controls (2.44 +/- 0.74 ml/min per g, P < 0.01) but
      not in jaundiced rats. Hepatic artery ligation did not affect blood flow or
      portal pressure either before or after resection. Small but significant portal
      systemic shunting was found in all jaundiced rats (2.19 +/- 2.1% vs. 0.026 +/-
      0.015%, P < 0.05). These results demonstrate that partial hepatectomy results in
      a significant increase in total liver blood flow. Acute cholestasis appears to
      prevent this increase. Even in the early stages of obstructive jaundice in the
      rat, there were signs of portal-systemic shunts.

PMID- 8151098
TI  - Grand mal seizures as a complication of treatment with pefloxacin in patients
      with cirrhosis. A report of three cases.
AB  - In this paper, three cases of grand mal seizures are reported as a complication
      of pefloxacin at usual doses (400 mg twice a day) in patients with cirrhosis.
      Grand mal seizures occurred from 12 h to 8 days after the onset of pefloxacin
      treatment. In 1 case, seizures recurred after inadvertent rechallenge with the
      drug. Elevated pefloxacin serum levels were demonstrated in 2 cases. Brain
      computed tomography in all 3 cases and cerebrospinal fluid examination showed
      normal results. No etiology other than pefloxacin overdose was found. After
      pefloxacin withdrawal, no recurrence of seizures were observed. Therefore, when
      pefloxacin treatment is indicated for cirrhotic patients, a reduced dosage and/or
      careful monitoring of pefloxacin serum levels should be recommended.

PMID- 8151099
TI  - Acetaldehyde-protein adducts, but not lactate and pyruvate, stimulate gene
      transcription of collagen and fibronectin in hepatic fat-storing cells.
AB  - Hepatic fibrosis is an important morphological feature of alcohol-induced liver
      injury. We previously reported that acetaldehyde, but not ethanol can stimulate
      type I collagen and fibronectin synthesis in cultures of rat fat-storing cells
      (FSC) by increasing transcription of the specific genes. The effect of lactate
      and pyruvate was studied on collagen I, III, fibronectin accumulation by cultured
      rat FSCs and it was investigated whether acetaldehyde could increase procollagen
      I and fibronectin gene transcription through the formation of protein adducts.
      Lactate and pyruvate (5, 15 and 25 mmol/l) did not significantly affect collagen
      I, III and fibronectin production by cultured FSCs. Pyridoxal-phosphate and p
      hydroxymecuribenzoate (inhibitors of acetaldehyde-protein adduct formation)
      blocked the stimulatory effect of acetaldehyde on procollagen I and fibronectin
      gene transcription. These data suggest that ethanol may act as a liver fibrogenic
      factor through acetaldehyde, its immediate metabolite, whereas lactate does not
      seem to play a role. Acetaldehyde might stimulate gene transcription of
      extracellular matrix components by liver FSCs through the formation of adducts
      with proteins.

PMID- 8151100
TI  - Protective effects of FUT-175 on acute massive hepatic necrosis induced in mice
      following endotoxin injection and immunization with liver proteins.
AB  - Experimental autoimmune hepatitis was induced in C57BL/6 mice by immunization
      with syngeneic liver protein and adjuvant. Hepatitis was characterized by marked
      cellular infiltrates, but hepatic necrosis was mild to moderate. A small dose of
      endotoxin (25 micrograms/mouse) produced lethal hepatitis with elevation of serum
      transaminase levels in these mice. The endotoxin-induced reactions were
      completely inhibited by i.p. administration of FUT-175 (5 mg/kg), a synthetic
      protease inhibitor, 1 h before the endotoxin injection. In vitro experiments
      showed that two-thirds of the inflammatory infiltrates were monocyte/macrophages.
      Cytotoxicity against syngeneic hepatocytes was significantly increased by the
      addition of endotoxin (25 micrograms/ml), but the same dose of endotoxin alone
      had no effect on the viability of hepatocytes. The endotoxin-induced increase in
      cytotoxicity was prominent in the glass-dish adherent (monocyte/macrophage
      enriched) fraction and was also demonstrated after depletion of T-cells. However,
      elevated cytotoxicity did not occur when FUT-175 (> 1 x 10(-7) M) was present
      throughout the assay period. These results seem to indicate that the hepatotoxic
      effects of endotoxin are mediated, at least in part, by monocytes or macrophages
      infiltrating the liver following immunization of liver proteins. Our results also
      suggest that FUT-175 has protective effects against endotoxin-induced hepatotoxic
      reactions.

PMID- 8151101
TI  - Autonomic and peripheral neuropathy in primary biliary cirrhosis.
AB  - Autonomic and peripheral nerve function was examined in a group of patients with
      primary biliary cirrhosis using standard cardiovascular reflex tests and
      peripheral nerve conduction studies. Sixty-three percent had cardiovascular
      autonomic dysfunction with predominantly parasympathetic abnormalities. Symptoms
      of peripheral neuropathy were rarely volunteered spontaneously but occurred
      frequently when specifically sought; 40.7% had definite peripheral neuropathy,
      with symptoms and/or signs plus peripheral neurophysiological abnormalities. A
      close association between autonomic and peripheral nerve function was found with
      correlation between the heart rate variation on deep breathing and both peroneal
      nerve conduction velocity (r = 0.67, P < 0.001) and sural nerve conduction
      velocity (r = 0.52, P < 0.008). Correlations were also noted between other
      autonomic tests and peripheral nerve function. Both autonomic and peripheral
      nerve function correlated with serum bilirubin and albumin; no significant
      association was noted with vitamin E deficiency or hyperlipidaemia. A generalised
      neuropathy with peripheral and autonomic abnormalities is common in primary
      biliary cirrhosis and could be related to hepatic damage. Although rarely
      clinically disabling, the autonomic impairment associated with this neuropathy
      may be of prognostic significance.

PMID- 8151102
TI  - Ribavirin in the treatment of chronic hepatitis C unresponsive to alfa
      interferon.
AB  - For the 30-50% of patients with chronic hepatitis C who do not respond to alpha
      interferon therapy there is no alternative treatment. Some previously untreated
      patients have shown a biochemical response to ribavirin, but the antiviral
      effects of this substance on alpha-interferon-resistant cases is largely unknown.
      Twelve patients with chronic hepatitis C who had not responded to a 6-12 month
      course of alpha-interferon were included in this study. Oral ribavirin was
      administered at a dose of 16 mg/kg per day for 6 or 9 months. Aminotransferase
      levels had not significantly changed during interferon therapy but decreased
      significantly during ribavirin treatment (mean alanine aminotransferase at
      baseline, 102 +/- 18 IU/l vs. 55 +/- 14 IU/l at 6 months; P = 0.0001).
      Aminotransferase levels became normal in 6 cases (50%), significantly decreased
      in 3 patients (25%), and did not significantly change in the remaining 3 cases
      (25%). All patients with normalized aminotransferase values relapsed after
      ribavirin was discontinued and aminotransferase activity returned to pretreatment
      levels. Before therapy serum hepatitis C virus RNA was detected by polymerase
      chain reaction in 10 cases. None of them had cleared viral RNA when tested
      following 3, 6 and 9 months of ribavirin therapy. Side-effects were mild and
      reversible. In conclusion, about half of the patients with chronic hepatitis C
      who are unresponsive to alpha-interferon show a clear-cut biochemical response
      after 6-9 months of ribavirin administration. However, ribavirin does not clear
      circulating hepatitis C virus RNA and relapses occur after withdrawal.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8151103
TI  - Effects of reserpine administration in two models of portal hypertension in rats.
AB  - The effects of reserpine were investigated in two models of portal hypertension
      in rats. Twenty-four hours after 1 mg/kg of reserpine was administered
      intraperitoneally to normal and portal vein stenosed rats, the cardiac index,
      mean arterial pressure, heart rate, and portal pressure were significantly
      decreased compared with normal and portal vein stenosed rats receiving placebo.
      In addition, the portal tributary blood flow was significantly decreased in
      portal vein stenosed rats receiving reserpine, but was unchanged in normal rats.
      In cirrhotic rats receiving a single dose of reserpine, 0.1 mg/kg
      intraperitoneally for 24 h, there were significant decreases in cardiac index,
      mean arterial pressure and heart rate compared with cirrhotic rats receiving
      placebo, while the portal pressure and portal tributary blood flow followed a
      decreasing trend after reserpine administration. The degree of hemodynamic change
      was similar in the groups of rats receiving reserpine, even though cirrhotic rats
      received lower doses than either normal or portal vein stenosed rats. This study
      suggests enhanced sympathetic nervous activity observed in cirrhotic rats.

PMID- 8151104
TI  - Effects of ornithine aspartate on plasma ammonia and plasma amino acids in
      patients with cirrhosis. A double-blind, randomized study using a four-fold
      crossover design.
AB  - This paper documents dose-dependent effects of ornithine aspartate (OA) on
      postprandial hyperammonemia and plasma amino acids. Ten patients with cirrhosis
      were randomized to undergo 1 out of 4 infusion series. Each series consisted of
      four 8-h infusions (09:00 h-17:00 h), with placebo (NaCl), 5 g, 20 g or 40 g of
      OA being administered on separate days in varying sequences. This 4-fold
      crossover design was double-blind. On infusion days, patients received 2 oral
      protein loads (0.25 g/kg at 09:00 h and 0.5 g/kg at 13:00 h). Venous blood
      samples were drawn every 2 h and the 24-h urine was collected. In addition to
      measuring plasma ammonia and amino acids, the urea production rate, serum glucose
      and serum insulin were analyzed. A significant postprandial rise in the ammonia
      concentration was noted during the infusions of placebo and 5 g of OA but did not
      occur with the dosages of 20 g (after the second protein load) and 40 g (after
      both protein loads). Furthermore, the latter dose, compared with placebo,
      significantly reduced plasma ammonia after the minor protein load. Urea
      production rate increased when 20 g or 40 g of OA was administered. Of the amino
      acids involved in the metabolic pathways of ornithine and/or aspartate, glutamate
      showed a rise in its plasma level following infusion of 40 g of OA, whereas
      glutamine did not. Concentrations of methionine, phenylalanine, tyrosine,
      threonine, serine and glycine declined progressively with increasing doses of OA
      (5-40 g). The highest dose of the drug caused hyperglycemia and
      hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151105
TI  - Treatment of chronic hepatitis B with recombinant interferon alpha versus
      recombinant interferon alpha plus levamisole.
AB  - To compare the efficacy and tolerance of the simultaneous administration of
      levamisole plus IFN versus treatment with IFN alone in chronic hepatitis B, 39
      patients were randomly assigned into two groups. Nineteen patients received 15
      million units of recombinant alpha interferon 2b (rIFN-alpha 2b) 3 times a week
      for 4 months. The other 20 patients were treated with the same dose and schedule
      of rIFN-alpha 2b and 150 mg of levamisole simultaneously given during the first 6
      weeks of treatment. At the end of the study (thirteenth month), serum HBV-DNA was
      negative in 59% of patients treated with interferon alone and in 37% of those
      treated with interferon and levamisole. HBeAg was negative in a similar
      percentage in the two groups (41% vs. 37%). Serum alanine aminotransferase levels
      decreased in patients who lost viral DNA. These data demonstrate that the
      combination of alpha interferon and levamisole, at the doses and under the
      schedule used in this study, does not achieve better results than the treatment
      with alpha interferon alone. Although tolerance to the simultaneous
      administration of alpha interferon and levamisole is good, secondary effects may
      be hazardous.

PMID- 8151106
TI  - Effect of orthotopic transplantation and chemical denervation of the liver on
      hepatic hemodynamics in the rat.
AB  - The involvement of the sympathetic nervous system in the control of basal hepatic
      hemodynamics was investigated. Hepatic denervation was achieved by orthotopic
      transplantation or chemical denervation of the organ. In male Lewis rats,
      transplantation with rearterialization of the graft was performed. Chemical
      denervation was achieved by intraportal injection of 6-hydroxydopamine (75
      mg/kg). Normal liver physiology was confirmed by histology and liver function
      tests. Four weeks post-transplantation and 7 days post-denervation, histological
      examination revealed no differences between transplanted, denervated and
      untreated or sham-operated control animals. Liver function measured by standard
      tests (e.g., plasma SGOT, bilirubin) was normal in all groups. The rate constants
      for aminopyrine breakdown in transplanted (0.015 +/- 0.005 min-1), denervated
      (0.015 +/- 0.0012 min-1) and control rats (0.015 +/- 0.001 min-1) were not
      significantly different. No significant difference in the rate of galactose
      breakdown was found. Total liver blood flow (measured by the 133Xe clearance
      technique in the anesthetized animal) was unaffected by transplantation (rate
      constant, 0.245 +/- 0.062 min-1; control 0.279 +/- 0.011 min-1). The interlobular
      distribution of portal blood flow was tested by intraportal injection of 51Cr
      labelled microspheres. A linear relationship between flow to lobe and lobe size
      was confirmed in control (r = 0.95), denervated, (r = 0.99) and transplanted rats
      (r = 0.97) and the 'relative' flow to each lobe was not significantly different
      in the 3 groups. No significant differences in the 'core' to 'periphery'
      distribution of portal blood flow were found in the 3 groups. A small but
      significant portal systemic shunt was found in transplanted but not denervated or
      control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151107
TI  - Ursodiol in the long-term treatment of chronic hepatitis: a double-blind
      multicenter clinical trial.
AB  - Ursodeoxycholic acid (UDCA or ursodiol) administration has been associated with a
      reduction of serum liver enzymes in patients with chronic liver disease and with
      improvement of liver histology in patients with primary biliary cirrhosis. To
      establish the potential therapeutic efficacy of ursodiol in chronic hepatitis,
      serum biochemistry and liver histology were investigated in a multicenter, double
      blind placebo controlled clinical trial. Sixty patients with non-cholestatic
      chronic active (mild or severe) hepatitis, mainly of viral (virus C) etiology and
      almost completely asymptomatic, were enrolled in 3 centers: 29 were assigned to
      receive placebo and 31 UDCA (600 mg/day) for 1 year. Demographic, biochemical,
      virological and histological features were balanced between the 2 groups at the
      entrance into the study. Fifty-six patients (34 males, 22 females; 19 with
      cirrhosis; 5 HBsAg-positive; 45 anti-HCV positive) were included in the final
      analysis. Compliance was checked by measuring UDCA levels at the 3 follow-up
      visits (3, 6 and 12 months). Liver biopsy was performed at the beginning and at
      the end of treatment and was evaluated blindly by our pathologist (F.C.). Alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and
      gammaglutamyltransferase (GGT) levels were significantly reduced by 25% from
      baseline values during treatment with ursodiol but not with placebo. The efficacy
      of UDCA in lowering serum AST and ALT was more pronounced in the presence of
      cirrhosis. The semiquantitative liver histological score used remained
      substantially unchanged after treatment and no differences between placebo and
      UDCA were found for portal or periportal necrosis or inflammation, intralobular
      degeneration, cholestasis or fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151108
TI  - Gallbladder responses to modified sham feeding: effects of the composition of a
      meal.
AB  - Changes in gallbladder contraction and plasma cholecystokinin release were
      studied following modified sham feeding of 3 different isocaloric meals rich in
      either fat, protein or carbohydrates in healthy volunteers, and results were
      compared with those following real feeding of comparable meals. In contrast to
      carbohydrate-rich meals (8 +/- 19 ml/120 min), fat- (-412 +/- 46 ml/120 min) and
      protein-rich meals (-352 +/- 42 ml/120 min) reduced integrated gallbladder volume
      (P < 0.05) in response to modified sham feeding. Plasma cholecystokinin levels
      were not significantly influenced by modified sham feeding of fat, protein or
      carbohydrates. Real feeding of a carbohydrate-rich meal also failed to
      significantly reduce gallbladder volume and to stimulate cholecystokinin release
      (-45 +/- 40 ml/120 min and 51 +/- 11 pmol/120 min, respectively), while real
      feeding of both fat- and protein-rich meals distinctly reduced gallbladder volume
      (-679 +/- 76 and -564 +/- 53 ml/120 min, respectively; P < 0.05) and increased
      cholecystokinin release (651 +/- 72 and 504 +/- 43 pmol/120 min, respectively; P
      < 0.05). This study demonstrates that gallbladder contraction during the cephalic
      phase of meal stimulation is dependent on the fat, protein and carbohydrate
      percentages of a meal, and is activated by different mechanisms than the
      intestinal phase of a meal.

PMID- 8151109
TI  - Dextropropoxyphene induced hepatotoxicity: a report of nine cases.
AB  - Nine patients are described with jaundice, upper abdominal pain and malaise
      attributable to dextropropoxyphene hepatotoxicity. In each case the history was
      suggestive of large bile duct obstruction. All patients underwent ultrasound
      examination and percutaneous liver biopsy. Three patients also underwent
      endoscopic retrograde cholangio pancreatography. The histological features of the
      biopsies concur with previously reported cases of dextropropoxyphene
      hepatotoxicity. The histological changes seen on biopsy were remarkably constant,
      consisting of centrilobular cholestasis, portal tract inflammation and bile duct
      abnormalities, in all cases mimicking large bile duct obstruction. Fifteen
      previous patients with probable dextropropoxyphene hepatotoxicity have been
      described. The occurrence of 9 further cases at one centre, 6 presenting within
      12 months, suggests that it is much more common than previously assumed and may
      be misdiagnosed as large bile duct obstruction.

PMID- 8151110
TI  - Modulation of protein kinase C alters hemodynamics and metabolism in the isolated
      liver in fed and fasted rats.
AB  - The activation of protein kinase C (PKC) has been implicated in the pathogenesis
      of gram-negative sepsis. The effects of PKC modulation on hepatic flow and
      metabolism were studied using isolated liver perfusion. The liver was isolated
      from well-fed or overnight-fasted, male Sprague-Dawley rats weighing 250-310 g,
      and perfused at a constant pressure of 12 cmH2O using a recirculating system.
      Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC, decreased
      hepatic flow and oxygen consumption, and increased net lactate production. It
      enhanced net glucose production in fed animals. Neither 4 alpha-phorbol
      didecanoate, an inactive phorbol ester for PKC nor 4 alpha-phorbol, an inactive
      phorbol had any significant effect. The effects of PMA were augmented by
      increasing calcium concentration in the medium. PMA at an initial concentration
      of 4 x 10(-8) M stimulated net lactate and/or glucose production more than a
      reduction of perfusion pressure from 12 to 6 cmH2O. Staurosporine, a potent PKC
      inhibitor, significantly attenuated the PMA-induced alterations of hepatic flow
      and oxygen consumption. These results indicate that modulation of PKC exerts
      significant effects on hepatic flow and metabolism, which are dependent on
      extracellular calcium concentrations and feeding conditions, and that the effect
      of PMA on carbohydrate metabolism is not merely attributed to decreases in
      hepatic flow and oxygen consumption. It is suggested that PKC activation may be
      involved in the alterations of hepatic flow and metabolism during severe sepsis.

PMID- 8151111
TI  - Selection for emergency liver transplantation.

PMID- 8151112
TI  - Prevalence of hepatitis C virus RNA in suspected drug induced liver diseases.

PMID- 8151113
TI  - Urinary copper excretion after penicillamine in the diagnosis of Wilson's disease
      in children.

PMID- 8151114
TI  - The languages of William Harvey's natural philosophy.

PMID- 8151115
TI  - Benjamin Perley Poore and his historical materials for a biography of W.T.G.
      Morton, M.D.

PMID- 8151116
TI  - The reorientation of medical education in late nineteenth-century Ontario: the
      proprietary medical schools and the founding of the Faculty of Medicine at the
      University of Toronto.

PMID- 8151117
TI  - "Country boys make the best nurses": nursing the insane in Alabama, 1861-1910.

PMID- 8151118
TI  - The molecular basis of metal recognition by T cells.
AB  - T lymphocytes play critical roles in a series of important immune responses,
      including delayed-type hypersensitivity and contact sensitivity. Metal haptens
      such as nickel are among the most common sensitizers. In general, T cells
      recognize fragments of proteins complexed to MHC molecules. Haptens, however, are
      too small to be antigenic by themselves. Recent experiments have suggested that
      hapten-specific T cells recognize hapten-modified MHC-peptide complexes. Here I
      review the data supporting this hypothesis and speculate on the relevance of
      these findings for the understanding of chemical-induced hypersensitivities.

PMID- 8151119
TI  - Ex vivo and in vivo gene transfer to the skin using replication-deficient
      recombinant adenovirus vectors.
AB  - The skin has the potential for a variety of gene therapy applications. In
      addition to local delivery, it is the largest organ of the body, and highly
      vascular, and thus is an ideal site for systemic delivery of gene products. To
      evaluate the potential for adenovirus-mediated skin gene transfer, the
      replication-deficient recombinant adenovirus vectors Ad.RSV beta gal (coding for
      Escherichia coli beta-galactosidase) and Ad alpha 1AT (coding for human alpha 1
      antitrypsin) were used in both ex vivo and in vivo approaches. Following in vitro
      infection with Ad.RSV beta gal, murine keratinocytes expressed beta
      galactosidase. Parallel in vitro studies with Ad alpha 1AT documented de novo
      synthesis and secretion of human alpha 1AT as shown by [35S]methionine labeling
      and immunoprecipitation. Quantification of human alpha 1AT in the culture
      supernatants demonstrated 0.1-0.3 microgram human alpha 1AT secreted/ml-24 h.
      Evaluation of the serum of mice receiving transplants (10(5) cells/mouse) of Ad
      alpha 1AT-infected syngeneic keratinocytes demonstrated human alpha 1AT for at
      least 14 d with maximum levels of 41 ng/ml. To demonstrate the feasibility of
      direct adenovirus-mediated in vivo transfer of genes to the skin, Ad.RSV beta gal
      or Ad alpha 1AT were administered subcutaneously to mice. Histologic evaluation
      after 4 d demonstrated expression of beta-galactosidase in various types of skin
      cells. Quantification of human alpha 1AT in serum of animals infected
      subcutaneously with Ad alpha 1AT showed levels of 53 ng/ml at day 4, with human
      alpha 1AT detectable for at least 14 d. These observations support the
      feasibility of ex vivo and in vivo gene transfer to the skin mediated by
      replication-deficient adenovirus vectors.

PMID- 8151120
TI  - UVB light induces nuclear factor kappa B (NF kappa B) activity independently from
      chromosomal DNA damage in cell-free cytosolic extracts.
AB  - It has been shown previously that ultraviolet (UV) light (290-320 nm) activates
      keratinocytes to release proinflammatory cytokines including interleukin (IL)-6.
      Because the 5' flanking region of the IL-6 gene contains a consensus NF kappa B
      binding sequence, the effect of UVB light on an NF kappa B-like binding activity
      was investigated in a human epidermoid carcinoma cell line (A431). Nuclear factor
      kappa B (NF kappa B) activation in the cytoplasm is known to be due to the
      dissociation of an inactive NF kappa B-inhibitor of nuclear factor kappa B (I
      kappa B) complex. Cytosolic extracts from cells harvested shortly after sublethal
      UVB irradiation showed a UVB dose-dependent increase of NF kappa B binding. The
      activation was reduced by radical scavenging chemicals, suggesting involvement of
      reactive oxygen intermediates. NF kappa B activation has been shown previously to
      be triggered by DNA lesions induced by UV light. To elucidate whether DNA damage
      is necessary and sufficient to mediate NF kappa B activation crude, cytosolic
      protein extracts obtained from unirradiated cells were exposed to UVB light. This
      in vitro UVB treatment led to activation of an NF kappa B-like binding activity,
      suggesting an additional signaling pathway independent of chromosomal DNA damage
      or byproducts of DNA damage. The activation process was dependent on the presence
      of membranes. The data suggest at least an additional signaling pathway for the
      early UVB response, including a component of the pathway residing at the cell
      membrane.

PMID- 8151121
TI  - p53 gene mutations in human skin cancers and precancerous lesions: comparison
      with immunohistochemical analysis.
AB  - Mutations of exons 3 through 9 of the p53 gene in skin lesions were screened in
      23 cases of squamous cell carcinoma (SCC), 25 cases of basal cell carcinoma
      (BCC), two cases of Bowen's disease, 10 cases of solar keratosis, and five cases
      of keratoacanthoma by polymerase chain reaction--single strand conformation
      polymorphism analysis. Mutations of the p53 gene were detected in seven of 23
      SCCs (30%), three of 25 BCCs (12%), and none in all cases of Bowen's disease,
      solar keratosis, or keratoacanthoma. Of 23 cases of SCC, mutations were detected
      in four of 15 SCCs (27%) that originated in the sunlight-exposed skin region, in
      two of three SCCs (67%) that originated in the scar tissue, and in one of three
      SCCs (33%) that originated in radiation dermatitis. Mutations of C-->T transition
      predominated in SCC and BCC that originated in the sunlight-exposed skin region.
      Mutations of C-->A or CC-->AT observed in tumors that originated in the
      predisposed conditions, presumably unrelated to UV light, are different from
      those found in UV light-related SCC or BCC. Twelve cases of SCC were
      comparatively analyzed with the immunohistochemical staining with anti-p53
      antibody. Two of four cases with positive staining had missense mutations, and
      three of eight cases with negative staining had nonsense mutations. Based on
      these findings, immunohistochemical results do not necessarily mean the presence
      or absence of p53 gene mutations in skin tumors, and sequence analysis is
      essential for determining whether the gene is mutated.

PMID- 8151122
TI  - Dose-response effects of acute ultraviolet irradiation on antioxidants and
      molecular markers of oxidation in murine epidermis and dermis.
AB  - There has not as yet been an integrated, comprehensive study of the responses of
      dermis and epidermis in vivo to a wide range of ultraviolet (UV) doses,
      encompassing all major antioxidants and a sensitive marker of oxidative damage.
      We have irradiated hairless mice with simulated solar light at doses of 2, 5,
      12.5, and 25 J/cm2 combined UVA and UVB (0.8 to 10 MED) and measured enzymic and
      non-enzymic antioxidants as well as lipid hydroperoxides in both epidermis and
      dermis to elucidate the response of cutaneous antioxidant defense mechanisms to
      UV stress. Among the nonenzymic antioxidants two different dose-response patterns
      were seen. Ascorbate was rapidly depleted at doses between 0 and 5 J/cm2 but was
      less affected between 5 and 25 J/cm2. In contrast, glutathione, ubiquinol/one,
      and alpha-tocopherol levels remained approximately equal to control levels
      between 0 and 5 J/cm2, then decreased to varying degrees from 5 to 25 J/cm2;
      ubiquinol was almost completely depleted, whereas alpha-tocopherol dropped only
      30%. The concentration of lipid hydroperoxides increased throughout the dose
      range. These results may be explained partly by direct destruction of some
      antioxidants by UV light, partly by the separate antioxidant functions of the
      compounds, and partly by recycling of some antioxidants (e.g., alpha-tocopherol)
      at the expense of others (e.g., ubiquinol). Even at the lowest dose (0.8 MED)
      lipid hydroperoxide formation was observed. Among the enzymic antioxidants,
      superoxide dismutase activity decreased significantly (to 63.6% of initial
      activity for epidermis and 51.5% for dermis at 25 J), whereas activities of
      glutathione peroxidase and glutathione reductase decreased slightly. Catalase
      activity decreased dramatically at doses above 5 J (to 11.8% of initial activity
      in epidermis and 27.7% in dermis at 25 J). The dramatic loss of catalase is
      almost entirely accounted for by direct destruction by the simulated solar light,
      but superoxide dismutase was unaffected by direct exposure; hence its destruction
      must be due to indirect effects, either mediated by free radicals or other
      harmful species formed upon irradiation. At low doses of UV light many components
      of the cutaneous antioxidant system were damaged, whereas at high doses all
      components were damaged and some were almost completely destroyed.

PMID- 8151123
TI  - Effect of age on antioxidants and molecular markers of oxidative damage in murine
      epidermis and dermis.
AB  - This is the first study of antioxidants and oxidative-damage-related parameters
      in epidermis and dermis of the skin as a function of age. The four major
      antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase, and
      glutathione peroxidase), hydrophilic and lipophilic antioxidants, and lipid
      hydroperoxides were assayed in both epidermis and dermis of young and old
      hairless mice. Catalase, superoxide dismutase, and glutathione reductase had
      similar activity levels in young and old animals. Only glutathione peroxidase
      from epidermis showed an activity decrease due to age. This decrease became
      apparent when enzyme activity was expressed per mg of total cellular protein.
      Hydrophilic and lipophilic antioxidants did not change as a function of age, nor
      did lipid hydroperoxide levels. Both the absolute level of oxidized glutathione
      and the ratio of oxidized to reduced glutathione were higher in dermis from old
      mice. These results suggest that skin aging is not accelerated in old age due to
      a general decrease in the antioxidant capacity of the tissue. The data are
      compatible, however, with the idea that continuous damage to skin tissue by free
      radicals occurs throughout an organism's lifetime because scavenging cannot be
      100% efficient.

PMID- 8151124
TI  - Molecular characterization of a ferrochelatase gene defect causing anomalous RNA
      splicing in erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria is an inherited disorder caused by deficient
      activity of the enzyme ferrochelatase. We have examined the ferrochelatase gene
      in an 11-year-old female with protoporphyria and have found that she is
      heterozygous for a mutation at a conserved residue in the exon 3 donor splice
      site consensus sequence (T(+2)-->G). This is inherited from her father, who also
      has deficient ferrochelatase activity. As a consequence of the mutation,
      ferrochelatase transcripts are aberrantly spliced and give rise to mRNA molecules
      in which sequences corresponding to exon 3 are absent. This leads to the
      expression of a ferrochelatase protein lacking a central region of 40 amino
      acids.

PMID- 8151125
TI  - Enhanced pyrimidine dimer repair in cultured murine epithelial cells transfected
      with the denV gene of bacteriophage T4.
AB  - The patch size for excision repair of ultraviolet radiation (UV)-induced
      pyrimidine dimers was determined in cultured murine epithelial cells with normal
      and enhanced pyrimidine dimer repair capabilities. Cells with enhanced pyrimidine
      dimer repair were produced by transfecting 308 cells with the denV gene of
      bacteriophage T4; this gene encodes the enzyme endonuclease V. Pyrimidine dimer
      repair following exposure to UV from an FS-40 sunlamp was determined by
      micrococcal dimer-specific nuclease digestion and alkaline sucrose
      ultracentrifugation. Patch size ws estimated based on the photolytic lability of
      bromodeoxyuridine-substituted DNA. Excision repair of UV-induced pyrimidine
      dimers in denV-transfected 308 cells was enhanced two- to threefold. Production
      of mRNA from the denV gene in cell lines with enhanced repair was confirmed by
      RNA blotting. In control cells, the patch size for excision repair of DNA
      photoproducts was estimated to be 34 nucleotides per photoproduct removed; in
      denV-transfected cells, a smaller average patch size of 10-16 nucleotides per
      photoproduct removed was calculated. Thus, endonuclease V activity appears to
      alter not only the extent, but also the nature of excision repair in UV-exposed
      mammalian epithelial cells.

PMID- 8151126
TI  - Phospholipid analogue hexadecylphosphocholine inhibits proliferation and
      phosphatidylcholine biosynthesis of human epidermal keratinocytes in vitro.
AB  - The alkylphospholipid hexadecylphosphocholine (HePC), member of a new class of
      antineoplastic drugs, has been previously shown to exert cytotoxic effects on
      neoplastic cell lines in vitro, and a selective antineoplastic activity has been
      reported after topical application of HePC in vivo, in particular on skin
      metastases of human mammary carcinomas. Preliminary observations suggest that
      HePC might also be beneficial in the treatment of non-neoplastic skin diseases
      characterized by epidermal hyperplasia such as psoriasis. Therefore, we
      investigated whether HePC might inhibit the proliferation of normal human
      keratinocytes, and whether its effects might be dependent upon the proliferative
      status of the treated cells. Moreover, its effects on phosphatidylcholine
      biosynthesis were studied in keratinocytes. HePC dose-dependently decreased cell
      numbers, thymidine incorporation, and protein synthesis when applied during the
      growth phase of keratinocytes grown in serum-free medium, with a minimal
      inhibitory dose of 10(-7) mol/l for thymidine incorporation, 3 x 10(-7) mol/l for
      cell numbers, and 10(-6) mol/l for 35S-methionine incorporation. No major
      differences were observed when keratinocytes were grown under high-Ca++
      conditions. In contrast, slowly proliferating confluent keratinocyte cultures
      showed growth inhibition only after 10(-4) mol/l HePC. Phosphatidylcholine
      biosynthesis was dose-dependently inhibited by HePC with a half inhibitory
      concentration of 3 x 10(-6) mol/l, and with translocation of the rate-limiting
      enzyme. CTP:phosphocholine cytidylyltransferase, to the cytosol, where the enzyme
      is inactive. These data show a pronounced antiproliferative effect of HePC also
      on proliferating non-malignant keratinocytes, and are compatible with its
      possible action on hyperproliferative skin disorders.

PMID- 8151127
TI  - Role of gene expression and protein synthesis of tyrosinase, TRP-1, lamp-1, and
      CD63 in UVB-induced melanogenesis in human melanomas.
AB  - Using melanotic cells (SK-MEL-23 and G361) and amelanotic cells (C32 and SK-MEL
      24) of human melanoma, this study examined whether UV-B irradiation has a direct
      stimulatory effect on the expression of genes involved in melanogenesis. Our
      initial screening of methylthiazol tetrazolium (MTT)-formazan formation assay
      indicated a low dose of ultraviolet (UV)-B irradiation, 2.5 and 5.0 mJ/cm2, can
      metabolically stimulate these cells. Repeated exposure of UV-B at 5.0 mJ/cm2 for
      seven consecutive days resulted in increased tyrosinase activity and melanin
      synthesis in SK-MEL-23 and G361 cells, but not in C32 and SK-MEL-24 cells. On
      reverse-transcription-polymerase chain reaction and immunoprecipitation studies,
      the two melanotic cell lines exhibited upregulated expression of mRNA and
      antigenic epitopes of tyrosinase, tyrosinase-related protein (TRP-1; gp75/HMSA
      5), and lysosomal membrane associated protein (Lamp-1). The amelanotic cell line,
      C32, expressed the tyrosinase gene and protein constitutively but revealed no
      active tyrosinase or melanin synthesis even after UV-B exposure. Another
      amelanotic cell line, SK-MEL-24, exhibited no expression of tyrosinase gene and
      protein before and after UV-B exposure and, therefore, no melanin synthesis. Both
      C32 and SK-MEL-24 showed no gene or protein expression of TRP-1 before or after
      UV exposure, but upregulation of the Lamp-1 gene and protein expressions after
      exposure. We conclude that tyrosinase is the key enzyme responsible for UVB
      induced melanogenesis. Both TRP-1 and Lamp-1 act together in melanogenesis, TRP-1
      being essential and necessary. There is no change in the expression of CD63
      lysosomal membrane protein at either the mRNA or protein level.

PMID- 8151128
TI  - High plasma level of a eumelanin precursor, 6-hydroxy-5-methoxyindole-2
      carboxylic acid as a prognostic marker for malignant melanoma.
AB  - Melanin synthesis is a biologic property unique to the melanocyte. It is highly
      elevated in malignant melanoma with the production of both eumelanin (brown/black
      pigment) and pheomelanin (yellow/red pigment), dihydroxyindole (DHI) and
      cysteinyldopa (CD), respectively, being major precursors. Melanin metabolites are
      often released in the urine of patients with disseminated melanoma metastasis
      (melanuria). To establish a better method for the detection of occult melanoma
      this study compares the plasma levels of a pheomelanin metabolite, 5-S-CD, and a
      eumelanin metabolite, 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C), in
      melanoma and non-melanoma patients and correlates them with tumor thickness and
      melanoma metastasis. We found a) that the normal plasma levels of 5-S-CD and
      6H5M12C are less than 2.22 ng/ml and 1.04 ng/ml, respectively; b) that the group
      with the normal 6H5MI2C plasma level does not have any metastasis, whereas a
      normal 5-S-CD level is seen in both non-melanoma and melanoma patients with and
      without metastasis; c) that a high plasma 6H5MI2C level is seen in all melanoma
      patients with tumor thickness more than 3.0 mm regardless of the presence or
      absence of metastasis, whereas in thinner melanoma patients this is seen only in
      positive metastasis group; and d) that all melanoma patients with positive
      metastases showed a high plasma 6H5MI2C level (more than 1.75 ng/ml). We conclude
      that the measurement of plasma levels of melanin metabolites provides a method
      for detecting occult melanoma metastasis and estimating the prognosis of melanoma
      patients, plasma 6H5MI2C level being more sensitive and reliable than that of 5-S
      CD, and its increased level being a high risk factor.

PMID- 8151129
TI  - Merkel cells of the terminal hair follicle of the adult human scalp.
AB  - Human scalp skins were treated with 20 mM ethylenediaminetetraacetic acid and
      terminal hair follicles were extracted with the epidermis. Some terminal hair
      follicles were morphologically preserved well and provided opportunity to examine
      three-dimensional distribution of CAM5.2 (K8, 52.5 kD) reactive Merkel cells. In
      anagen terminal hair of the scalp numerous immunoreactive Merkel cells were
      distributed in the presumptive bulge area. Distinct swelling as in the bulge of
      human vellus hair was usually absent; however, in rare instances anagen terminal
      hair demonstrated unilateral prominent swelling with dense aggregation of Merkel
      cells. In telogen hair the bulge becomes indistinguishable from the regressed end
      of the club hair follicle but Merkel cells continued to be abundant. We found
      morphologic variation of the bulge such as formation of knoblike swellings and
      villous projections. Interestingly, Merkel cells were also located in these
      structures. Palisading stockade-like nerve endings were observed surrounding the
      follicular epithelium at the sebaceous gland level. Merkel cells were sparse in
      this follicular segment. Variable number of Merkel cells were also scattered in
      the infundibulum of terminal hair in no association with peripheral nerves.

PMID- 8151130
TI  - Immunocytochemical localization of androgen receptors in the scalp of the
      stumptail macaque monkey, a model of androgenetic alopecia.
AB  - The purpose of this study was to identify the distribution of androgen receptors
      in the bald and hairy scalp of adult male and female stumptail macaque monkeys by
      light microscopic biotin-avidin immunocytochemistry with a highly purified rat
      monoclonal antibody against the cloned human androgen receptor. Consistent,
      intense nuclear and minimal cytoplasmic immunostaining was observed in several
      distinct cell populations of the pilosebaceous unit including the dermal papilla,
      hair epithelium, outer root sheath, dermal sheath, and sebaceous gland. A similar
      distribution of androgen receptors was found in miniaturized and terminal anagen
      and telogen follicles of the bald and hairy scalp, respectively. Binding of
      androgen receptor antibody was also detected in dermal fibroblasts, basal and
      intermediate layers of the interfollicular epidermis, and duct and glandular
      cells of eccrine sweat glands. This investigation demonstrates the presence of
      androgen receptors in the pilosebaceous unit of the scalp of the stumptail
      macaque and also shows that their distribution is comparable to that previously
      reported for humans.

PMID- 8151131
TI  - Use of a human skin-grafted nude mouse model for the evaluation of topical
      retinoic acid treatment.
AB  - Cultured human keratinocytes and artificial dermal equivalents maintained in
      vitro do not perfectly mimic the terminal differentiation patterns and response
      to drugs observed in intact human skin. We have made use of human skin grafted
      onto nude mice to demonstrate that such grafts maintain the pattern of
      pharmacologic responsiveness to all-trans retinoic acid previously reported in
      human subjects. The use of a quantitative polymerase chain reaction method to
      measure induction of a retinoic acid responsive gene, cytoplasmic retinoic acid
      binding protein II, has made it possible to generate objective data suitable for
      investigations of drug efficacy. This method of using grafted human skin has
      potential broad applicability for investigation of topical drugs in a number of
      therapeutic fields.

PMID- 8151132
TI  - The receptor for urokinase-type plasminogen activator is expressed by
      keratinocytes at the leading edge during re-epithelialization of mouse skin
      wounds.
AB  - Expression of urokinase-type plasminogen activator receptor mRNA was examined in
      vivo in mouse skin wounds by in situ hybridization. Urokinase-type plasminogen
      activator receptor mRNA was found in keratinocytes at the front of the
      regenerative epithelial outgrowths at the edge of 12-, 48-, and 96-hour-old
      wounds. The signal was strongest in the keratinocytes just beginning to move 12 h
      after wounding. At later time-points the signal was weaker, but still confined to
      keratinocytes at the wound edges. Using in situ hybridization, no cells
      expressing urokinase-type plasminogen activator receptor mRNA could be detected
      in normal epidermis, in normal-looking epidermis adjacent to the wounds, in
      dermis, in subcutis, or in newly formed granulation tissue. The specificity of
      the results was supported by the use of antisense RNA from two different non
      overlapping cDNA clones and the corresponding sense RNA probes, and by Northern
      analysis of tissue extracts. Together with previous findings on expression of
      urokinase-type plasminogen activator and its type 1 inhibitor, the localized and
      regulated expression of urokinase-type plasminogen activator receptor mRNA during
      skin wound healing indicates that focal extracellular proteolysis at the cell
      surface generated by receptor-bound urokinase-type plasminogen activator is
      implicated in the migration of re-epithelializing keratinocytes.

PMID- 8151133
TI  - U937 cells can utilize plasminogen activator to regulate human interferon-gamma.
AB  - Urokinase-type plasminogen activator (uPA) converts the proenzyme plasminogen to
      plasmin and thereby contributes to processes like cell migration, tissue
      remodeling, and cytokine processing. We report here that uPA produced by the
      human U937 promonocytic cell line also initiated the inactivation of recombinant
      interferon-gamma (rIFN-gamma) by plasmin-mediated proteolysis. When cultured
      serum-free with plasminogen, U937 promonocytic cells generated measurable levels
      of plasmin activity and destroyed the antiviral activity of exogenously added
      rIFN-gamma. This effect was not seen in the absence of plasminogen, was prevented
      by inhibitors of uPA and plasmin, and was accompanied by changes in the
      electrophoretic mobility of rIFN-gamma on polyacrylamide gels, consistent with
      limited proteolysis of the lymphokine. Culturing U937 cells or blood monocytes
      for 48 h led to an elevated expression of their surface uPA and an increase in
      their capacity to produce plasmin and inactivate rIFN-gamma. The ability of rIFN
      gamma to induce Fc receptors on U937 cells could also be prevented by providing
      the cells with a source of exogenous plasminogen, indicating that U937 cells
      could control their own activation in vitro through the action of uPA. The
      results of these studies support the conclusion that mononuclear phagocytes have
      the capacity to use uPA to regulate cytokine activity in vitro.

PMID- 8151134
TI  - Superinduction of mitogen-stimulated interferon-gamma production and other
      lymphokines by Sendai virus.
AB  - We observed that Sendai virus preinduction of peripheral blood mononuclear cells
      and subsequent mitogenic stimulation resulted in: (i) Superproduction of
      interferon-gamma, (IFN-gamma) (ii) an increase in interleukin-2 (IL-2) synthesis
      that correlates with DNA synthesis when stimulated with phytohemagglutinin (PHA)
      or pokeweed mitogen (PWM) after treatment with the Sendai virus, while
      stimulation with Protein A from Staphylococcus aureus was not affected, and (iii)
      enhanced tumor necrosis factor-alpha (TNF-alpha) production in response to
      bacterial lipopolysaccharide (LPS). Treatment of monocyte cultures with LPS and
      cycloheximide or actinomycin-D inhibited the superinduction phenomenon. When
      cycloheximide was added at the viral induction time, the inhibition of TNF-alpha
      superproduction and DNA synthesis was still observed. These results suggest that
      Sendai virus lymphocyte superinduction is specific for a particular stimulatory
      pathway, not dependent on mRNA accumulation, and probably mediated by induction
      of an activating protein.

PMID- 8151135
TI  - Interferon induction by viruses. XXII. Vesicular stomatitis virus-Indiana: M
      protein and leader RNA do not regulate interferon induction in chicken embryo
      cells.
AB  - Several field isolates, strains, mutants, and revertants of vesicular stomatitis
      virus (VSV), Indiana (IN) serotype, were studied that differed greatly in their
      capacity to induce interferon (IFN) in aged chick embryo cells. The predicted M
      protein amino acid sequence of a wild-type field isolate that induced > or =
      10,000 units/ml IFN in chicken embryo cells was identical to that of a wild-type
      field isolate that induced < 2 units/ml and of a noninducing wild-type laboratory
      strain. The 47-base plus-strand leader RNA sequences were the same for five IFN
      inducing, and eight noninducing independent isolates of wild-type VSV IN. Our
      data show that the M-protein and plus-strand leader RNA do not of themselves
      regulate the induction of IFN in this system. Because the capacity of VSV IN to
      induce IFN resides in virion-associated elements (Marcus and Sekellick, 1987, J.
      Interferon Res. 7, 269-284), the differences in IFN yield observed with various
      isolates must result from changes in other virion components that remain to be
      determined.

PMID- 8151136
TI  - Xanthine oxidase does not mediate the antiproliferative effects of interferon
      gamma in human umbilical vein endothelial cells.
AB  - Interferon-gamma (IFN-gamma) has potent antiproliferative effects on the
      endothelium, although the specific mechanisms responsible for this effect are not
      clear. We tested the hypothesis that suppression of endothelial cell
      proliferation by IFN-gamma is mediated by an increase in xanthine oxidase-derived
      O2-.. Human umbilical vein endothelial cells (HUVEC) were exposed to recombinant
      human IFN-gamma. We found that [3H]thymidine uptake decreased (p < 0.05) with
      increasing doses of IFN-gamma. Treatment of HUVEC with the xanthine oxidase
      inhibitor allopurinol or the O2-. scavenger superoxide dismutase had no effect (p
      > 0.05) on [3H]thymidine uptake of IFN-gamma-treated cells. In parallel, IFN
      gamma decreased (p < 0.05) HUVEC cell counts, while allopurinol again had no
      effect (p > 0.05) on cell counts of IFN-gamma-treated or control HUVEC. In
      addition, xanthine oxidase activity of HUVEC did not (p > 0.05) increase
      following treatment with IFN-gamma. We conclude that IFN-gamma suppresses HUVEC
      proliferation by a mechanism independent of O2-. production by xanthine oxidase.

PMID- 8151137
TI  - Induction of interferon in human leukocyte cultures by natural pathogenic
      respiratory viruses.
AB  - Some common viruses responsible for respiratory disease have been reported to be
      poor inducers of interferon (IFN). Therefore, we have studied the induction of
      IFN in cultures of human leukocytes exposed under standardized conditions to
      various concentrations of adenovirus type 7A, coronavirus 229E, an influenza type
      A virus (H3N2), a rhinovirus, and respiratory syncytial virus (RSV). All five
      viruses induced substantial amounts of IFN at a multiplicity of infection of one
      infectious unit per cell or less. Leukocyte cultures from 50 healthy children
      were exposed to a standard concentration of each of the viruses. IFN was induced
      almost without an exception, but the amounts produced varied extensively
      according to both the virus and the individual leukocyte donor.

PMID- 8151138
TI  - Effect of interferon-gamma on membrane conformation in the macrophage-like cell
      line P388D.
AB  - Interferon-gamma (IFN-gamma) specifically induced the uptake of the unsaturated
      fatty acid [14C]linoleic acid into membrane phospholipids of the murine
      macrophage-like P388D cell lineage, but did not alter the incorporation of the
      saturated fatty acid [14C]stearic acid. Spin label ESR spectroscopy was used to
      examine any effects of these IFN-gamma-induced changes on membrane fluidity and
      the results revealed significant increases in plasma membrane fluidity. This
      alteration in membrane fluidity may have important consequences in the dynamic
      properties of cellular physiochemical interactions and some of the stimulatory
      effects of IFN-gamma on macrophages might be attributed to its effects on the
      plasma membrane composition.

PMID- 8151139
TI  - Expression and regulation of an interferon-alpha-inducible membrane protein p106
      on human hematopoietic cells.
AB  - p106 is a human membrane protein of 106 kD previously shown to be inducible by
      interferon-alpha (IFN-alpha) on Daudi cells. To investigate the role of p106
      further, its distribution and inducibility within hematopoietic cells was
      studied. Multiparameter flow cytometry (FCM) analysis showed that p106 expression
      was restricted to B cells and monocytes, and in both cell lineages acquired at a
      late stage of differentiation. Thus, p106 was found on mature B lymphocytes and
      monocytes in peripheral blood and on a variety of freshly isolated leukemic cells
      of B and myeloid origin as well as on a variety of cultured B-cell lines. In
      contrast, no expression was found on T lymphocytes, natural killer (NK) cells or
      granulocytes. p106 expression could be further induced by IFN-alpha on monocytes
      and Daudi cells, and this capacity was shown to be selective for IFN-alpha, since
      no other cytokines tested induced p106. Moreover, IFN-alpha therapy of chronic
      myeloid leukemia (CML) and hairy cell leukemia (HCL) patients lead to a clearcut
      induction of p106 on such malignant cells. The distribution of p106 could suggest
      that it represents an activation antigen. Further studies, including cloning of
      p106 cDNA, are needed to determine the function of p106.

PMID- 8151140
TI  - Nomenclature of the human interferon genes.

PMID- 8151141
TI  - [A prospective study of septic episodes due to Staphylococcus aureus and the
      background of the patients].
AB  - From January 1983 to December 1991, 94 cases of Staphylococcus aureus septicemia
      were identified at Matsue Red Cross Hospital and were evaluated. Methicillin
      resistant Staphylococci aureus counted 49%. Seventy two percent of the patients
      were 60 years or over in age. Intravascular catheters were the most common foci
      (33%), respiratory infections in 25% and so on. Administration of antibiotics
      before isolation of Staphylococcus aureus were thought to be the most significant
      factor in producing the methicillin-resistant septicemia, used in 41% of MSSA and
      91.3% of MRSA cases. Especially, the trend of unproper usage of the 3rd
      generation cephems derivative antibiotics had a major role in producing multi
      drug resistant bacteria. No significance was seen in the clinical background,
      underlying diseases, primary site of infection in between the two groups of
      methicillin resistant and sensitive cases. Mortality due to septicemia was 47.9%
      in the MSSA group of patients, while it was much higher in cases of MRSA (73.9%).
      In conclusion, as the administration of antibiotics even in non-infectious
      episodes is common in daily clinical activities in some out-patient clinics, the
      indications should be restricted, in order to prevent the further MRSA
      infections.

PMID- 8151142
TI  - [Bacterial contamination of hair washing liquids].
AB  - To determine the extent of contamination by bacteria of hair-washing shampoo and
      rinse used professionally at barber shops and hair-dressing saloons, quantitative
      isolation of bacteria were performed by using a total of 39 samples of shampoo
      and rinse fluid obtained from 17 facilities. It was found that a maximal number
      of 1 x 10(7)/ml colony forming units/ml of bacteria were isolated from 60.7% (17
      out of 28 samples) of the shampoo and 45.5% (5 out of 11) of the rinse. Gram
      negative bacilli were the predominant strains (87.9%) involved in bacterial
      contamination and the major isolates were Serratia marcescens (43.3%, most
      frequently isolated), Pseudomonas cepacia, P. fluorescens, P. aeruginosa and
      Klebsiella pneumoniae, all which are widely recognized as nosocomial-infection
      causing pathogens. These results indicate hair-washing liquids for professional
      use are contaminated with a great number of gram-negative bacteria, being
      possible causes of nosocomial infections, and much attention should be paid to
      the sanitation and cleanliness of the shampoo and rinse for hair-washing.

PMID- 8151143
TI  - [Formation of drug-induced serotype variants of Pseudomonas aeruginosa: changes
      in biochemical properties, drug susceptibility and outer membrane proteins].
AB  - The serotype variants were formed in some isolates of Pseudomonas aeruginosa in
      the presence of anti-pseudomonal drugs in vitro. Pyocin type, various biochemical
      properties and drug susceptibility of these variants were compared with those of
      the parent cells. Furthermore, the patterns of outer membrane proteins were also
      examined for some respective parent and variant cells by the SDS-PAGE and
      compared with their drug susceptibilities. In P. aeruginosa No. 1-S (serotype E)
      and No. 1-R (serotype C), simultaneously isolated from the identical specimen of
      the infectious patient, the serotype variants were formed by anti-pseudomonal
      drugs and accompanied by changes in pyocin types, some biochemical properties and
      susceptibilities to various kinds of anti-pseudomonal drugs. When the profiles of
      outer membrane proteins of P. aeruginosa No. 1-R parent and two variant cells
      were evaluated by the SDS-PAGE, the quantitative differences of the porin
      proteins between the parent and variant cells were well related to their drug
      susceptibilities. Although eight variant cells with other serotype were formed
      from the parent cells (serotype A) of P. aeruginosa No. 13, four variants with
      serotype M and one non-typable variant showed changes in drug susceptibility such
      as resistance to imipenem only and no changes in biochemical properties. On the
      other hand, three other variants showed marked changes in two kinds of
      biochemical properties and in susceptibilities to various kinds of anti
      pseudomonal drugs. From the results of SDS-PAGE, it was found that the porin
      protein profiles of outer membranes of these parent and variant cells except a
      few cells which corresponded to their drug susceptibility.

PMID- 8151144
TI  - [Effect of 14-member lactone ring macrolides on anti staphylococcal activity and
      swarming ability of Pseudomonas aeruginosa].
AB  - The purpose of this report is to examine the effect of Macrolides (Erythromycin
      and Roxythromycin) on swarming ability and antistaphylococcal activity of
      Pseudomonas aeruginosa. The standard strain (ATCC27854) and clinically isolated
      P. aeruginosa were used as test strains. The influence of Macrolides on
      antistaphylococcal activity and swarming ability were determined by the agar
      plate dilution method. The antistaphylococcal activity of P. aeruginosa was not
      affected at the concentration of 1.56 micrograms/ml of both Erythromycin and
      Roxythromycin. But the antistaphylococcal activity was not observed at the
      concentration over 100 micrograms/ml. The swarming ability was not affected at
      the concentration up to 12.5 micrograms/ml. It has been proved that Macrolides
      reveal inhibition of virulent factors of P. aeruginosa such as protease,
      elastase, piocianin and so on. Furthermore our data revealed that Macrolides
      inhibited swarming ability of P. aeruginosa, and did not affect the
      antistaphylococcal activity of P. aeruginosa under 1.56 micrograms/ml
      concentration. Consequently, these results suggest that Macrolides have exhibited
      a previously unknown pharmacological effect, and may be of interest in that there
      may be bacterial interaction between MRSA and P. aeruginosa.

PMID- 8151145
TI  - [Viral etiology in travellers' diarrhea].
AB  - Virological examinations were performed on stools obtained from 1,264 overseas
      travellers with diarrhea at Nagoya International Airport between 1986 and 1991.
      Group A rotavirus was detected in 11 samples (0.87%) by latex agglutination
      method, but other viral agents such as atypical rotaviruses and small round
      structured viruses were not observed by electron microscopic analysis.
      Rotaviruses were detected in various age groups, but the positive rate of
      rotavirus in females (6/398) was higher than that in males (5/866). Seasonal
      variation in the detection of rotavirus was observed. Entero 71 was isolated from
      one of 11 rotavirus-positive cases, but the other 10 cases were not associated
      with enteroviruses. All rotavirus-positive cases were negative for isolation of
      enteropathogenic bacteria.

PMID- 8151146
TI  - [Susceptibility to macrolides against Mycoplasma pneumoniae isolated during 7
      years].
AB  - The efficacies of macrolide antibiotics, rokitamycin, leukomycin, josamycin and
      erythromycin were investigated against 63 strains of M. pneumoniae included FH
      strain which were isolated from clinical specimens obtained in 1986-1987, 1991,
      1992-1993. Values of MICs and MBCs of these antibiotics were evaluated by two
      methods, broth dilution method and M. pneumoniae L cell infection system. In
      broth dilution method, MIC50 and MBC50 of rokitamycin were 0.0063-0.025
      microgram/ml and 0.025-0.2 microgram/ml respectively. The ratios of MBC50/MIC50
      were 1-32. MIC50 of leukomycin, josamycin and erythromycin were 0.0063-0.05
      micrograms/ml, 0.0025-0.05 microgram/ml, and 0.0125-0.05 microgram/ml
      respectively. MBC50 of these drugs were 0.0125-50 micrograms/ml, 25-50
      micrograms/ml, and 25-50 micrograms/ml respectively. The ratios of MIC50/MBC50
      were 2-800, 500-2000, 500-4000. MIC50 of rokitamycin and leukomycin to the
      isolates during period from 1992-1993 were higher as compare to those of isolates
      during 1986 to 1991. On the other hand, rokitamycin markedly reduced the numbers
      of CFU in the growth phase when added at the concentrations of 16 and 4 times the
      MIC, but the other macrolides were reduced slightly CFU at the concentrations of
      4 times, the MIC. In L cell infectious system, MIC50 and MBC50 of rokitamycin
      were 0.005-0.0125 microgram/ml and 0.05-0.1 microgram/ml respectively. The ratios
      of MBC50/MIC50 were 1-2 Ratios of leukomycin, josamycin, and erythromycin were
      0.05-0.1 microgram/ml, 0.05-0.2 microgram/ml and 0.050-0.1 microgram/ml
      respectively. The MBC50 of these drugs were 0.2-0.4 micrograms/ml, 0.8-1.6
      microgram/ml, 0.8-1.6 microgram/ml. Ratios of MBC50/MIC50 were 2-8, 4-32, 8
      32.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151147
TI  - [Mechanism of efficacy of erythromycin on diffuse panbronchiolitis--effect of
      erythromycin on cytokine mRNA expression in human whole blood model].
AB  - Recently, "low-dose and long-term" erythromycin (EM) has been reported to be
      effective in treatment of diffuse panbronchiolitis (DPB), but its mechanism is
      still obscure. We studied the effect of EM on cytokine mRNA expression by using
      LPS-stimulated human whole blood as an experimental vivo model. IL-8 mRNA was
      expressed in biphasic fashion with peak expression at 6 hours and 20 hours from
      the start of LPS stimulation. When whole blood was pretreated with EM (2
      micrograms/ml) for 1 hours. IL-8 mRNA expression was depressed at 20 hours (p <
      0.025) from the start of LPS (1 microgram/ml) stimulation. However, when
      pretreated for 12 hours, it was not depressed. EM (2 micrograms/ml) also
      depressed IL-1 beta (p < 0.025) and TNF alpha (p < 0.05) mRNA expressions at 6
      hours from the start of LPS stimulation. From the above results, it was suggested
      that the direct inhibition of IL-1 beta and TNF alpha production by EM resulted
      in subsequent depression of production of IL-8 that is a potent chemotactic
      factor for neutrophil, and consequently, EM acts to protect the bronchiole
      tissues of DPB patients from destruction by proteolytic enzymes released from
      neutrophils. This assumption seems to be supported by our previous observation
      that when patients with DPB were treated with EM a marked decrease in number of
      neutrophil in bronchoalveolar lavage fluid (BALF) was accompanied by clinical and
      radiographic improvement.

PMID- 8151148
TI  - [Coexisting respiratory tract infection and bacteremia or sepsis caused by the
      same bacterium].
AB  - We experienced 12 patients who were suffering from bacteremia or sepsis and
      pneumonia or lung abscess coincidently caused by the same bacterium, during the 8
      years from 1985 to 1992 a Hokusyo Central Hospital. All of them has some
      underlying diseases, and the average age was 73.6 years old. In ten out of 12
      patients bacteremia or sepsis preceded the respiratory tract infection, and in 7
      cases indwelling intravenous catheter was thought to be the port of entry of the
      bacteria. Respiratory tract infections were composed of pneumonia in 8 cases and
      lung abscess in 4 cases. Methicillin resistant Staphylococcus aureus (MRSA) was
      detected in 4 cases, Methicillin sensitive Staphylococcus aureus (MRSA),
      Klebsiella pneumoniae and Pseudomonas aeruginosa were in 2 cases respectively,
      Citrobacter freundii and Methicillin resistant Staphylococcus spp. were in one
      cases respectively. Eight out of 12 cases died in spite of current antibiotics
      therapy, suggesting poor prognosis.

PMID- 8151149
TI  - [Thirty seven cases of respiratory syncytial virus infection hospitalised and 7
      severe cases with apneic attacks].
AB  - We studied 37 cases of respiratory syncytial virus infection hospitalized during
      the period January 1, 1989 and March 31, 1993. 37 patients were 0-4 years old on
      admission. Fever, positive CRP and elevation of BSG were frequent in patients
      aged 8 months-4 years old. Patient more than 8 months of age didn't need
      supplementation of oxygen. Of the 37 patients, we had one case who had
      hyponatremia and six cases who were admitted with severe apneic attacks required
      incubation. Of the six cases, one patient had delayed neurological deterioration
      after anoxia due to apneic attacks. He, followed up for 4 years, have serious
      residual deficits including spastic quadriplegia, delayed development and
      epilepsy. Variety of factors, including premature birth, young postnatal age and
      milk feeding appeared to be significant risk factors for sever infections of RSV.
      In RSV infection, apneic attacks can cause near-miss SIDS. So, we stress the
      importance of careful and rapid diagnosis for all infants less than 8 months of
      age.

PMID- 8151150
TI  - [Clinical evaluation of aciclovir granules in the treatment of chickenpox in
      otherwise healthy children].
AB  - The efficacy and safety of aciclovir granules (containing 40% w/w aciclovir) were
      evaluated in the treatment of chickenpox in otherwise healthy children. Patients
      presenting with chickenpox received aciclovir granules at a dose of 20 mg/kg four
      times daily for five to seven days. Overall 51 children received treatment with
      aciclovir. A further 53 patients receiving conventional symptomatic therapy acted
      as a control. In the aciclovir group the overall efficacy rate was 92.2%. There
      were reductions in the numbers of lesions, fever, itching and the duration of
      symptoms. No adverse experiences were reported. Overall this formulation of
      aciclovir appears to be a safe and effective treatment for chickenpox in this
      patient population. However the need for anti-viral therapy in otherwise healthy
      children is still the subject of debate and it might be appropriate to identify
      sub-groups for whom such therapy is justified.

PMID- 8151151
TI  - [Three cases of Pasteurella multocida infection in the respiratory tract].
AB  - Pasteurella multocida (P. multocida) is well recognized as "normal flora" in the
      upper respiratory tract of cats, dogs and other animals. Recently, various
      infections due to P. multocida in human have been noted as pulmonary infections
      in the patients with chronic pulmonary diseases as well as skin abscesses or
      septicemia after an animal bite or scratch. We report here three cases of
      respiratory tract infections caused by P. multocida. The first two patients had
      acute exacerbation of bronchiectasis caused by P. multocida and the other
      patients with pulmonary emphysema developed pneumonia. These three patients
      improved by antibiotic therapy. In Japan, P. multocida respiratory tract
      infection is rare, but it may become more common in the future. Therefore, it
      seems to be important to take this pathogen into consideration in the management
      of chronic lung disease.

PMID- 8151152
TI  - [Two cases of Campylobacter fetus subsp. fetus sepsis].
AB  - We encountered two relatively rare cases of sepsis due to Campylobacter fetus
      subsp. fetus (C. fetus). Case 1. A 54-year-old female with abdominal polysurgery
      developed a slight fever and vomiting in August 1984. Despite the administration
      of some digestive drugs by her family doctor, these symptoms continued. In mid
      October, she was hospitalized with high fever with chill and rigor on the skin.
      On the third hospital day, C. fetus was detected in the blood culture. After
      combination chemotherapy of intravenous drip infusion of latamoxef (LMOX) (2
      g/day) and oral administration of erythromycin (EM) (800 mg/day), her symptoms
      improved. Case 2. A 57-year-old male with diabetic retinopathy and nephropathy
      was hospitalized because of slight fever, general edema and pleural effusion. On
      the 6th hospital day, C. fetus was detected in the blood culture and he was
      diagnosed with sepsis. Under treatment with the intravenous drip of LMOX (2
      g/day) and oral administration of EM (1200 mg/day), his condition improved. Both
      cases had common underlying diseases such as hypoproteinemia with edema and
      problems in the lower intestinal tract; the former had polysurgery and
      malabsorption syndrome, the latter had diffuse ulceration of the colon. Such
      underlying conditions may have permitted the invasion of C. fetus into the blood.

PMID- 8151153
TI  - [A case of brain abscess associated with enterococcal endocarditis].
AB  - Enterococcal infections involving the central nervous system are uncommon
      clinical entities. A 74-year-old male was admitted to our hospital on November 3,
      1991 for high fever. Nuchal rigidity was observed at neurological examination.
      All four blood cultures yielded E. faecalis. The MIC value of ABPC against the
      isolated E. faecalis was 0.25 microgram/ml. Vegetation on the mitral valve and
      mitral regurgitation were revealed by an echocardiogram. Enhanced CT scan showed
      low density area with ring enhancement in the right basal ganglia and a CSF
      examination suggested bacterial meningitis. He became better after ABPC 8 g/day
      was intravenously administered. Then the vegetation on the mitral valve and the
      brain abscess disappeared. He was discharged with no complications. We reported a
      rare case of brain abscess associated with enterococcal endocarditis.

PMID- 8151154
TI  - [A case report of infant botulism without a history of honey ingestion].
AB  - A 66-day-old female with infant botulism is reported. She was admitted to our
      hospital with respiratory failure. Laboratory examinations detected botulinal
      toxin type A in her feces. This was the first case with no history of honey
      ingestion among the 13 cases of infant botulism reported in Japan. It is possible
      that other cases, in which honey had not been consumed, remain undiagnosed.
      Further studies may be needed to clarify the factors necessary to cause infant
      botulism.

PMID- 8151155
TI  - [A case of NIDDM with non-clostridial gas-producing infection in the lower limb-
      the effects of hyperbaric oxygen therapy].
AB  - A 36-year-old male was admitted because of swelling and pain in the lower left
      limb. He had been diagnosed as having non-insulin dependent diabetes mellitus 4
      years previously and had been treated unsuccessfully with insulin. Since gas
      formation was radiographically demonstrated in the soft tissue of the left foot,
      we treated him with antibiotics and hyperbaric oxygen under the diagnosis of gas
      gangrene. Despite this therapy, the gangrenous lesions progressed. Amputation of
      the left foot was necessary. Peptstreptococcus was isolated from the gangrenous
      area and identified as such on the seven hospital day. Nine cases of diabetic
      patients with non-clostridial gas gangrene who were treated with hyperbaric
      oxygen therapy have been reported in Japan. The results indicated that hyperbaric
      oxygen therapy is ineffective in the treatment of non-clostridial gas gangrene in
      diabetic patients.

PMID- 8151156
TI  - Locus- and allele-specific DNA-protein interactions in the HLA-DQB1 X box.
AB  - Expression of MHC class II genes is regulated by a complex series of protein-DNA
      interactions which lead to the initiation of transcription. Although the
      different MHC class II loci are generally coordinately expressed, important
      differences in expression can be seen among loci and among individual alleles.
      The major sites of transcriptional control in the human MHC consist of several
      highly conserved nucleotide sequence elements located upstream of each MHC class
      II gene. We have analyzed the interlocus and interallelic variation in one of
      these key regulatory regions of the HLA-DQB1 promoter, the X box, and identified
      several sites of protein-DNA interaction. Two protein-DNA complexes were found
      which differ between the DQ and DR loci as well as two distinct complexes which
      differed between DQ alleles. These nuclear protein-X box interactions are likely
      to influence the differential expression of the MHC class II loci and alleles in
      tissue-specific or developmentally regulated pathways.

PMID- 8151157
TI  - The detection of antithyroglobulin activity in human serum monoclonal
      immunoglobulins (monoclonal gammopathies).
AB  - The sera of 159 patients with monoclonal gammopathies were examined for the
      presence of anti-thyroglobulin (Tg) activity. An enzyme-linked immunosorbent
      assay was employed. Thirty-one (19.5%) sera were found to bind Tg. The activity
      against Tg was further confirmed by using purified immunoglobulins and employing
      competition assays. The anti-Tg antibodies were found in the sera of patients
      with IgG, IgM and IgA gammopathies. Anti-Tg antibodies were more frequent among
      patients with IgG gammopathy. Autoantibodies to Tg are found in patients with
      Hashimoto's thyroiditis, Graves' disease and occasionally in patients with
      thyroid carcinoma. Natural autoantibodies directed against human Tg have been
      detected, as well, in healthy subjects. None of the patients in the present study
      whose serum was found to contain high titers of anti-Tg human monoclonal
      antibodies had any clinical or biochemical evidence of thyroid disease. Our
      results of a high incidence of anti-Tg activity in the sera of patients with
      monoclonal gammopathies support previous reports of autoantibody properties
      characteristic of these immunoglobulins.

PMID- 8151158
TI  - Immunoregulatory characteristics of the in vitro anti-ssDNA response.
AB  - Continuous blockade of B-cell antigen receptors (BCRs) with Fab alpha sIg
      prevents the anti-ssDNA response of high, but not low, density B cells. Signaling
      via the BCRs, by prior exposure to crosslinking F(ab')2 alpha sIg, had no effect
      on the spontaneous anti-DNA response, but prevented a lipopolysaccharide-induced
      anti-DNA response. Pretreatment with intact alpha sIg, which provides exogenously
      derived Fc signals, reduced the response. An Fc-signal-blocking agent, F(ab')2
      anti-IgG-Fc antibody, increased the number of anti-DNA antibody-forming cells
      produced in the absence of exogenous IgG anti-ssDNA antibody. Thus, activation is
      dependent on the availability of the BCRs, prior BCR crosslinking does not
      interfere with activation, and endogenous IgG anti-ssDNA antibody limits the
      activation of anti-ssDNA-specific B cells most of which are T-cell independent.
      These results indicate that the anti-ssDNA response is driven through the BCR.

PMID- 8151160
TI  - Special issue on endovascular surgery.

PMID- 8151159
TI  - Vitamin E supplementation modulates cytokine production by thymocytes during
      murine AIDS.
AB  - Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS,
      which is functionally similar to human AIDS. Retrovirus infection targeted the
      thymus, producing altered T cell differentiation via the dysregulation of
      thymocyte cytokine production. Human AIDS causes vitamin deficiencies, therefore
      the effects of dietary vitamin E supplementation were determined on the kinetics
      of cytokine production by concanavalin A-stimulated thymocytes in uninfected
      normal mice and mice with murine AIDS. Dietary supplementation, with a 15-fold
      increase in vitamin E (160 IU/l) in the liquid diet (National Research Council),
      modulated interleukin-2 (IL) production in both uninfected mice and retrovirus
      infected mice. Vitamin E significantly reduced the level of IL-4 secretion in the
      uninfected mice at 4 and 8 weeks, but not at 12 and 16 weeks. It also
      significantly reduced IL-4 production, elevated by retrovirus infection. Vitamin
      E significantly reduced IL-6, and interferon-gamma production increased in murine
      AIDS. The effects of dietary vitamin E on concanavalin A-induced proliferation of
      thymocytes were consistent with the finding of changes in IL-2 secretion. No
      effects of dietary vitamin E on thymus weight were observed in uninfected or
      retrovirus-infected mice, whereas vitamin E significantly increased serum and
      thymic vitamin E concentration, which had been reduced by retrovirus infection.
      These data indicate that dietary vitamin E supplementation can modulate cytokine
      production by thymocytes, affecting T cell differentiation, especially during
      retrovirus-induced immune dysfunction.

PMID- 8151161
TI  - Endovascular surgery: history, current status and future perspective.

PMID- 8151162
TI  - The current role of vascular stents.
AB  - The limitations of percutaneous balloon angioplasty have favoured the development
      and the use of vascular endoprostheses or stents. These thin-walled metal devices
      maintain after expansion, an optimal and constant diameter for the vascular
      lumen. Restenosis, dissection, abrupt closure, residual stenosis or re-opened
      total occlusion represent appropriate indications for stenting. A large
      experience with non-coronary application of stents is currently available in
      iliac, femoro-popliteal and renal arteries, aorta, large veins.

PMID- 8151163
TI  - Intravascular ultrasound imaging: an essential component of angioplasty
      assessment and vascular stent deployment.
AB  - Potential early complications of balloon angioplasty include occlusion due to
      vessel wall recoil, medial dissection, creation of intimal flaps, spasm and
      luminal thrombosis. These features have also been implicated in the development
      of restenosis and late occlusion. As a possible solution to these problems, an
      endovascular scaffold (stent) was proposed by Dotter in the 1960s, and initial
      studies suggested that use of such a device in specific circumstances may reduce
      complications related to major dissection, vessel recoil and spams. This paper
      reports the utility of two- and three-dimensional intravascular ultrasound (IVUS)
      imaging in assessing arterial morphology following balloon angioplasty, and
      guiding the need for, and adequacy of deployment of intravascular stents. IVUS
      imaging provides a technique to accurately assess the immediate results of
      angioplasty and examine both the luminal size and contour following intervention.
      Accurate imaging such as this is essential for the successful use of balloon
      expandable stents, by ensuring correct initial positioning and complete
      deployment at the time of balloon expansion. Two cases are reported which
      highlight the important issues which are critical to the ongoing development of
      endovascular therapies: (i) accurate assessment of the angioplasty results, and
      (ii) selection and confirmation of stent deployment. We conclude that IVUS
      imaging may provide a new standard for the assessment of angioplasty procedures
      and will play a pivotal role in identifying failure mechanisms of endovascular
      interventions.

PMID- 8151164
TI  - The role of endovascular therapy in lower extremity revascularization. Lessons
      learned and current strategies.
AB  - Percutaneous endovascular therapy has emerged as an important modality in the
      treatment of lower extremity ischemia. Its role is relatively small but better
      defined at present. Balloon angioplasty remains as the most useful and versatile
      of all catheter interventions. Common iliac artery lesions, if short and
      stenotic, are best managed with angioplasty. Percutaneous therapy of femoral
      popliteal lesions is less satisfactory but applicable in a small subset of
      patients with favorable lesions. Intravascular stents and thrombolysis are viewed
      as major developments in the field. Critically ischemic limbs are seldom amenable
      to endovascular recanalization. The subspecialty of endovascular therapy should
      become increasingly the focus of attention by the contemporary vascular surgeon.
      Catheter technology is destined to influence profoundly current strategies and
      techniques in the treatment of vascular diseases.

PMID- 8151165
TI  - Percutaneous peripheral rotational ablation using the Rotablator: immediate and
      mid term results. Single center experience concerning 146 lesions treated.
AB  - In order to assess the role of percutaneous peripheral rotational ablation using
      Rotablator (PPRA), 95 symptomatic patients (58 M, 37 F, m. age: 77 +/- 1 y) (r:
      50-90 y) having 146 peripheral vascular lesions (PVL) were treated by PPRA. 59%
      were below the knee and 41% above. The runoff status (n of distal leg art.
      involved) was as follows: 3:52 pts, 2:23 pts, 1:14 pts, 0:6 pts. The femoral
      lesions were significantly longer than those at other sites (5.27 +/- 0.43 vs
      2.97 +/- 0.3 cm) (p < 0.001). The mean length was 3.73 +/- 0.26 cm (r: 1-20 cm).
      Complementary PTA was significantly (p < 0.001) more frequent in femoro-popliteal
      (32 PTA/48 Fem, 5 PTA/12 Pop) than in distal leg lesions (10/86.). RESULTS. After
      PPRA alone (99 PVL) the stenosis % decreased from 81 +/- 0.75 to 18 +/- 1.1. The
      residual stenosis was greater at femoral (26 +/- 2.3%) than at distal leg level
      (16 +/- 1.2%) (p < 0.01). Complementary PTA (47 PVL) lowered residual stenosis
      from 44% to 13%. 52 complications (spasm, perforation, dissection, distal emboli,
      no reflow, others) were cured in 47 PVL. Thus our primary technical success per
      PVL was 97% and per pt 95%. The mean follow-up period was 11 +/- 1 mths (r: 1-37
      m). Among 78 pts having a follow-up period > or = 4 mths, 74 pts representing 115
      treated PVL underwent an angiography control (2 deaths, 2 lost for follow-up). 87
      lesions (76%) showed no restenosis and 28 lesions (34%) showed restenosis of 83
      +/- 2.4% (r: 50-100%). The restenosis rate was higher in femoral (12/21: 36%)
      than in distal (15/58: 21%) or popliteal arteries (1/8: 12%). Restenosis was more
      frequent for PVL > or = 7 cm (67% vs 16%) (p < 0.001) at all sites. This result
      together with the complication rate would seem to indicate that lesions > or =
      6.7 cm would be a limitation for PPRA. CONCLUSIONS. In our experience
      Percutaneous Peripheral Rotational Ablation has taken a pre-eminent position in
      the treatment of distal leg arteries. Our results lead us to broaden its
      indications to complex vascular lesions. The possibility of runoff treatment
      should allow an improvement in the long-term patency of PTA and bypass grafts.

PMID- 8151166
TI  - Intravascular ultrasound imaging: development and clinical applications.
AB  - Intravascular ultrasound is an exciting, new catheter based technique for imaging
      blood vessels. It provides accurate, real-time information about the types and
      distribution of vascular disease and displays both the macro- and micro-structure
      of blood vessels utilizating transducer frequencies of 10 MHz to 50 MHz. This
      paper discusses the development and current clinical applications of
      intravascular ultrasound technology, based on early intracardiac devices in the
      1950s and resulting in very small diameter (1.3 mm), flexible probes in the 1990s
      for use in coronary and small peripheral vessels. Preliminary studies have
      established the dimensional accuracy of intravascular ultrasound, and more recent
      techniques such as three-dimensional image reconstruction have produced a very
      powerful research and clinical tool. The value of intravascular ultrasound in the
      diagnosis and therapy of vascular disease is based on its ability to define the
      transmural distribution of disease within the vessel, characterize plaque and
      intimal lesions, and provide accurate cross-sectional information regarding
      luminal and vessel wall morphology before and after intervention. Major
      priorities in the ongoing development of intravascular ultrasound are the need
      for further miniaturization and cost-effective manufacturing. Future angioplasty
      guidance devices may combine the benefits of angioscopy and intravascular
      ultrasound in a single delivery system suitable for incorporation into any
      ablative (mechanical or laser) catheter.

PMID- 8151167
TI  - Percutaneous transluminal angioplasty of the brachiocephalic vessels: guidelines
      for therapy.
AB  - Angioplasty of the brachiocephalic vessels has been utilized in the treatment of
      stenotic/occlusive lesions for the past twelve years. The guidelines for use of
      PTA therapy versus surgery, however, have not been well defined. Multiple
      pathologies and morphologies for the various lesions have been described. The
      location of the lesion on the brachiocephalic chain plays a role. In our study of
      131 brachiocephalic vessels (66 subclavian, 3 axillary, 3 brachial, 35 vertebral,
      9 innominate, 6 common carotid, 7 internal carotid and 2 external carotid), we
      successfully dilated 93% (122/131) of all vessel stenoses/occlusions. Our success
      rate varied, however, with the severity, pathology, and location of the lesion.
      [We experienced greater success with stenotic versus occlusions (98%, 118/121 for
      stenotic lesions, versus 40%, 4/10 for total occlusions)]. In addition, we
      experienced only 2 complications in our series, a thromboembolism to the arm, and
      one patient with temporary bilateral blindness. Both patients experienced full
      recovery. Following PTA therapy, a 5 year follow-up was attempted. Although not
      complete, we have documented only 5 patients with restenoses at the site of
      original angioplasty. The restenoses occurred at 3, 6, 8, 12, and 18 months post
      procedure. Two of the long-term failures were from totally occluded vessels.
      Through our results, as well as a thorough review of the current literature, we
      have defined five lesions in which PTA therapy would be superior to surgical
      intervention.

PMID- 8151168
TI  - Endovascular techniques for abdominal aortic occlusions.
AB  - The application of endovascular interventions is spreading to encompass more
      anatomic locations and a wider array of vascular pathologies. The combination of
      thrombolysis with intraluminal devices has been an important factor in applying
      interventional therapy to abdominal aortic occlusive disease, where such
      intraluminal options can reduce the need for abdominal surgery. Seven patients
      with total abdominal aortic occlusions were treated with antegrade, high-dose
      urokinase infusion delivered to the clot site over a 20-48 hour period prior to
      balloon dilation and Palmaz stent implantation for unresolved pressure gradients,
      residual plaque, lesion recoil, or dissection. Lytic therapy cleared the thrombus
      totally in 6 patients and sufficiently in the 7th to facilitate retrograde iliac
      artery wire passage. All 7 patients required stent implantation to maximize
      revascularization (11 stents deployed in the abdominal aorta and 10 in the common
      iliac arteries). There were 2 instances of post-procedural distal embolization
      attributable to the thrombolysis, but both were treated satisfactorily. In up to
      28 months of follow-up, all patients remain asymptomatic. Combining lytic therapy
      and stenting extends the applicability of endovascular interventions to patients
      with aortic occlusion.

PMID- 8151169
TI  - Limb salvage: thrombolysoangioplasty as an alternative to amputation.
AB  - OBJECTIVE: This 5-year retrospective study evaluates the results of
      thrombolysoangioplasty (TLA) used as an alternative to major amputation in
      patients with severely debilitating, lower extremity, peripheral vascular
      disease. All patients in this study were originally designated for major
      amputation to treat their ischemic symptoms after all other surgical options were
      exhausted. MATERIALS AND METHODS: Twenty-one limbs in 20 patients with complete
      occlusions of the superficial femoral, popliteal and at least 2 of the 3 major
      branches below the popliteal trifurcation were attempted for
      thrombolysoangioplasty for limb salvage. The majority of patients had previous
      bypass procedures, and all patients had either nonhealing ischemic ulcers, tissue
      loss, and/or resting pain. RESULTS: There were no primary failures. 17/21
      patients were saved from major amputation. 4/21 patients were changed from an AKA
      to a BKA. 5/21 patients reoccluded within 1 year. 4/5 were successfully retreated
      via TLA. 1/5 required a major amputation. Life Table analysis demonstrated 63.6%
      (+/- 3.72)-12 months and 45.4% (+/- 3.78)-15 months primary patency rates. Limb
      salvage rates, however, were significantly better. Twenty-four month and 31 month
      rates of 75.5% (+/- 5.57) and 75.5% (+/- 6.44) were seen for complete limb
      salvage, respectively, while 24 and 40 months partial limb salvage rates of 94.7%
      (+/- 3.67) and 94.7% (+/- 4.27) were demonstrated. There were 2 complications;
      they were both retroperitoneal hemorrhages. Both patients recovered without
      sequelae. DISCUSSION: In conclusion, these preliminary results indicate that TLA
      is an effective alternative to major amputation for patients with severely
      debilitating peripheral vascular disease.

PMID- 8151170
TI  - [Cyclooxygenase in ooplasm is essential for early embryonal differentiation but
      not for successful fertilization in the mouse].
AB  - It has been known that inhibition of prostaglandin (PG) synthesis interferes with
      successful implantation. The present study dealt with the chronology in
      cyclooxygenase (COX) expression and the effects of inhibition in mouse oocytes in
      the perifertilization period. COX protein was detected in both oocytes and
      fertilized eggs whereas the mRNA was not found by a high sensitivity RT-PCR only
      in blastocysts. Oocytes which were sham operated or micro-injected with
      preabsorbed anti-COX monoclonal antibody (hPES01) or non-immune IgG were
      fertilized and developed to two-cell embryos, whereas hPES01 injected oocytes
      were fertilized but failed to differentiate (p < 0.05 chi 2-analysis). This
      inhibitory effect on early embryonal development of COX inhibition was also seen
      in indomethacin pre-cultured oocytes which were successfully fertilized but
      failed to develop further. We concluded that the COX gene which is one of the
      immediate early genes is not transcribed in the perifertilization period but the
      enzyme which remains in the cytoplasm and the presence of intact COX before
      fertilization are essential for early embryonal differentiation.

PMID- 8151171
TI  - [Aggressive management of prolapsed fetal membranes earlier than 26 weeks'
      gestation by emergent McDonald cerclage combined with amniocentesis and bladder
      overfilling].
AB  - During the period January, 1987-December, 1992, 32 pregnant women (33 fetuses)
      earlier than 26 weeks' gestation were admitted to our perinatal unit with
      incompetent cervix and prolapsed fetal membranes through the cervix
      (hourglassing). Eighteen pregnant women (19 fetuses) were managed aggressively
      with emergent double McDonald cerclage, which included preoperative amniocentesis
      and bladder overfilling to decompress and replace prolapsed fetal membranes.
      Fourteen pregnant women were managed conservatively with bed rest, tocolysis, and
      antibiotic therapy. The perinatal results of aggressive management were clearly
      more favorable than those of conservative management when compared: Prolongation
      of pregnancy 35.2 +/- 39.7 vs. 3.5 +/- 2.6 days (p < 0.01), gestational age at
      delivery 27.3 +/- 5.3 vs. 24.2 +/- 1.2 weeks' (p < 0.05), birth weight 1,260 +/-
      909 vs. 690 +/- 124 grams (p < 0.05), and fetal salvage rates 74(14/19) vs.
      7(1/14)%, respectively.

PMID- 8151172
TI  - [Ultrasonographic blood flow velocimetry in maternal and umbilical arteries
      during maternal exercise].
AB  - To see hemodynamic changes induced by exercise in pregnant women, we performed
      blood flow velocimetry with an ultrasonic pulsed Doppler in femoral (FA),
      external carotid (CA), uterine (UA) and umbilical arteries (Umb A) of pregnant
      women before and after aerobic dancing at an intensity of approximately 65%
      maximal heart rates. The subjects were 21 volunteer pregnant women at from 34 to
      40 weeks of gestation without obstetrical problems. The velocimetry was done at
      intervals of five minutes for only one artery of the four arteries. The
      measurement was repeated 4 times. The following results were obtained: (1) Both
      pulse rates and blood pressure (BP) increased significantly five minutes after
      the onset of exercise (p < 0.05) and tachycardia continued for 20 minutes. The
      intensity of exercise was equivalent to 68.8 +/- 1.1% of the maximal heart rates
      (mean +/- S.E.). (2) Systolic peak velocity in the FA of the pregnant women
      increased by 130%, flow volume per minute jumped by 337% (p < 0.05), and the
      pulsatility index (PI) decreased by 80% (p < 0.05). (3) Neither the systolic peak
      velocity nor the PI of CA and UA changed significantly. (4) The FHR became
      tachycardic due to exercise from 142.2 +/- 2.5 bpm to 161.1 +/- 3.8 bpm,
      associated with the increase in maternal pulse rates. (5) The PI of Umb A was
      decreased from 0.95 +/- 0.04 to 0.80 +/- 0.03 by exercise. The PI showed a
      negative correlation (r = -0.37, p < 0.05) with the FHR, not different from a
      correlation shown without exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151173
TI  - [Lipids metabolism evaluated of by vitamin E to total lipid ratio in maternal and
      cord sera in normal pregnancy].
AB  - Changes in plasma levels of lipids peroxide (LPO) and vitamin E(VE) are observed
      in pregnant women. We measured levels of VE and lipids in 80 maternal and cord
      sera in normal delivery and obtained the following results. 1. For each lipid and
      VE, the concentration gradients were preserved in maternal sera to cord sera
      through placentas. 2. The concentration of VE correlated with that of total
      lipids (TL) in both sera. 3. The VE to TL ratio (VE/TL ratio) inversely
      correlated with the concentration of LPO in both sera. 4. The concentration of VE
      correlated with the VE/TL ratio and there was a more significant correlation of
      the VE and VE/TL ratio than that of VE and TL in both sera. 5. The VE/TL ratio in
      maternal serum correlated with VE/TL ratio and the concentration of VE in cord
      serum. These results suggested that lipids in serum was a regulatory factor in VE
      and that VE and lipids maintained the gradation of the concentration according to
      their own placental transport systems. It seems that the fetus has a unique VE
      which is comparatively lowered. This may be due to the effects of the accelerated
      lipid metabolism in the fetus.

PMID- 8151174
TI  - [Histological analysis of spontaneous adenomyosis-like changes in recombinant
      inbred mouse uterus (SMXA mouse)--a novel animal model for adenomyosis].
AB  - The etiology and the pathogenesis of adenomyosis, which is a benign uterine
      disease featuring the ectopic proliferation of endometrial tissues and glands
      into the myometrium and the serosa in the uterus, are still unknown. A novel
      mouse strain, which showed signs of a condition resembling adenomyosis, was found
      and the localization of alpha-actin and tenascin was analyzed in order to
      characterize the histological features of this disease. 1. The uteri of
      recombinant inbred SMXA mice were shown to have undergone spontaneous
      histological changes similar to adenomyosis. 2. Compared with SMXA mice, the
      uteri of F1 mice between the SMXA and NJL strains showed further prominent
      changes resembling human adenomyosis, which suggests that some hereditary factors
      may be involved in the pathogenesis of adenomyosis. 3. In a normal mouse uterus,
      the regions in which tenascin was expressed change with the estrus cycle. In SMXA
      mice, tenascin was expressed around the dysplastic and cystic uterine glands, and
      in the myometrium. These results indicated that tenascin is an important marker
      of the histological changes in adenomyosis. 4. SMXA mice, which are recombinant
      inbred mice, are shown to be a useful animal model to use in analyzing the
      pathogenetic mechanisms of adenomyosis.

PMID- 8151175
TI  - [Usefulness of CA125 determination in the diagnosis of lymph node metastasis in
      post menopausal uterine endometrial carcinoma].
AB  - It has been difficult to diagnose all but advanced cases of lymph node metastases
      with CT or MRI. It has been reported that the serum value of CA125 rises with the
      stage of endometrial cancer. This level is lower in the postmenopausal period
      than before menopause. In this study, we have examined the usefulness of CA125
      for the assessment of lymph node metastasis in 43 postmenopausal endometrial
      cancer cases. There were significant differences in the CA125 level between lymph
      node metastasis positive cases and negative cases, between cancers occupying > or
      = 1/2 and < 1/2 of the uterine cavity, between lesions of > or = 1/3 and < 1/3
      depth, and between surgical stages I, and III and IV. There was no significant
      correlation between serum CA125 levels and histological type. The serum CA125
      value (mean +/- S.D., U/ml) was 179.0 +/- 291.0 (N = 6) in cases with lymph node
      metastasis and 15.8 +/- 8.5 (N = 37) in cases without metastasis (p < 0.001). We
      concluded that 32U/ml, which equals the mean + 2S.D., is a useful cut off value
      for suspicion of lymph node metastasis. The sensitivity and specificity of this
      cut off value were 100 (6/6) and 91.9% (34/37), respectively. This standard seems
      likely to considerably increase the accuracy of diagnosis of lymph node
      metastasis when taken in combination with the several factors already known to
      predict this. It may also be useful to diagnose lymph node metastasis in the
      preoperative period. Although the number of cases in this study was small, the
      data seem very promising for planning therapy for individual cases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8151176
TI  - [A study on the distribution of metastases at autopsy in 70 patients with ovarian
      cancer].
AB  - A total of 6,457 autopsy protocols were reviewed to identify 70 women who died of
      ovarian cancer. 1. Epithelial tumors were the most common tumor (74%). Twenty%
      were germ cell tumors. There were two cases each of sarcoma and stromal cell
      tumors. 2. The patients with germ cell tumors were younger than those with
      epithelial tumors. The duration of the epithelial tumor disease was longer than
      that of germ cell tumor. 3. The most common mechanism of death was carcinomatosis
      (69%). Eight of 70 patients (11%) had respiratory failure. One case of subacute
      cor pulmonale was due to tumor embolization. One case had a rupture of the portal
      vein. 4. The peritoneum was most frequently involved in every tumor (87%). The
      liver was the second most frequent site (73%). Other frequent metastatic sites
      included the lungs (44%), and spleen (47%). Lymph nodes including the paraaortic,
      pelvic and mesenteric were also very frequent metastatic sites. 5. CDDP
      containing regimens were used in 33 cases (47%). FAMT regimen was the second most
      common treatment (15.7%). Another common treatment is whole abdominal
      radiotherapy (14%). The patients treated with the CDDP containing regimen had a
      significantly longer survival time (23.4 months) than those treated with FAMT
      (19.2 months) and others (13.6 months). 6. For metastasis to the lungs, spleen
      and mesenteric lymph nodes the patients treated with the CDDP containing regimen
      were more numerous than those treated without CDDP. For metastasis to the
      kidneys, the patients treated without CDDP were more numerous than those treated
      with CDDP containing regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151177
TI  - [Pregnancy after frozen-thawed embryo transfer to endometrium controlled by the
      replacement of exogenous ovarian steroid hormones].

PMID- 8151178
TI  - [Prenatal diagnosis of arachnoid cyst of quadrigeminal cistern: a case report].

PMID- 8151179
TI  - [Clinical study on residual ovary syndrome].

PMID- 8151180
TI  - [Evaluation of CO2 laser conization for pregnant women with cervical
      intraepithelial neoplasia].

PMID- 8151181
TI  - [Total laparoscopic hysterectomy].

PMID- 8151182
TI  - [Laparoscopic salpingo-oophorectomy (adnexectomy) with percutaneous organ
      extraction instruments].

PMID- 8151184
TI  - Case-control study of BCG vaccination as a risk factor for leprosy and
      tuberculosis in western Kenya.
AB  - A case-control study was carried out in western Kenya to measure the protection
      imparted by BCG against leprosy and tuberculosis. The study involved 69 newly
      diagnosed leprosy cases, 238 age-, sex- and neighborhood-matched controls, and
      144 newly diagnosed, sputum-smear-positive tuberculosis cases along with 432 age
      , sex- and neighborhood-matched controls. Information on BCG vaccination history
      was inferred from scars. Using matched analysis, the protection imparted by BCG
      against leprosy was estimated to be 81% [95% confidence interval (CI) = 67-90]
      with no apparent difference in protection against paucibacillary [vaccine
      efficacy (VE) = 83%, 95% CI = 58-92] and multibacillary leprosy (VE = 76%; 95% CI
      = 30-91). The effectiveness against tuberculosis was appreciably lower (VE = 22%)
      and was not statistically significant (95% CI = -20-51).

PMID- 8151183
TI  - Low predictive value of PGL-I serology for the early diagnosis of leprosy in
      family contacts: results of a 10-year prospective field study in French
      Polynesia.
AB  - In 1983, a cohort study to follow up the family contacts of leprosy cases was
      implemented in French Polynesia to assess the usefulness and applicability of
      phenolic glycolipid-I (PGL-I) serology in a leprosy control program. A total of
      1201 contacts (666 females, 535 males) have been included in the study. The IgM
      anti-PGL-I seroprevalence determined on the initial sera was 17%. It was
      significantly higher among females than males (20% vs 15%, p = 0.02). From 1983
      to 1992, 4 out of 204 (2%) anti-PGL-I seropositive contacts developed the disease
      (1 indeterminate, 1 BT, 1 BL, 1 LL) compared with 10 out of 997 (1%) seronegative
      contacts (4 indeterminate, 3 BT, 1 BB, 2 TT). Of these 10 patients, only 3 (2
      indeterminate, 1 BT) converted to seropositivity when leprosy was diagnosed. The
      risk of developing leprosy was not significantly higher among seropositive than
      among seronegative groups (2% vs 1%, p = 0.2). A PGL-I circulating antigen test
      performed on 216 selected sera at entry into the trial showed a higher antigen
      prevalence when the antibody level was higher. PGL-I antigen was detectable in 5
      of 12 patients tested prior to diagnosis (1 LL, 1 BL, 3 indeterminate). The
      median time to externalize the disease was not significantly different among
      antibody-positive and -negative contacts (17 vs 25 months, p = 0.3). The relative
      risk of developing leprosy for contact individuals was 30.8 times that of
      noncontacts, and 15% of the total new cases detected between 1983 and 1992
      emerged from the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151185
TI  - Intrafamilial transmission of leprosy in Vellore Town, India.
AB  - A hospital-based study was done from 1968 to 1991 to determine the risk and
      extent of intrafamilial transmission of leprosy in relation to the
      characteristics of the index cases and contacts in urban areas in India. Families
      were examined by doctors annually. Skin smears were done for contacts of
      multibacillary (MB) leprosy patients. Person years of follow up were computed for
      each contact and used as the denominator for computation of incidence rates.
      Specific rates were computed by age, sex, type of leprosy, smear in index cases,
      age at registration, and sex of contacts. Of the 120 index cases (81 males, 39
      females) 44% were MB; 410 contacts (186 males, 224 females) and 14 co-prevalent
      cases were registered. The cumulative years of follow up was 2725 years. Fourteen
      contacts developed the disease (9 TT, 3 indeterminate, and 2 BT); 85.7% were in
      the 0-14 age group; 12 of 14 patients were detected to have leprosy during the
      first 5 years. The incidence rate (IR) was 5.1/1000 (males 5.15, females 5.12).
      The IR was 7.3/1000 and 2.3/1000 among contacts of MB and paucibacillary leprosy
      patients (p < 0.05). The IR in multiple-case families was 1.8. The importance of
      active surveillance by a hospital-based survey is emphasized. It should be
      designed to focus on children younger than 15 years and should be limited to 5
      years of follow up.

PMID- 8151186
TI  - HIV-1 infection as a risk factor for leprosy; a case-control study in Tanzania.
AB  - A case-control study was carried out in Tanzania to determine the relative risk
      of those with HIV-1 infection for getting leprosy. Cases were 93 consecutively
      diagnosed patients with leprosy aged 15-54 years from the Mwanza Region. Controls
      were a representative population sample of 4161 people drawn from a stratified
      cluster sample from urban areas, roadside settlements, and rural villages. HIV-1
      infection was determined by enzyme-linked immunosorbent assay (ELISA); Western
      blot was used when the ELISA result was indeterminate. The HIV-1 prevalence in
      leprosy cases was 10% in rural (7 of 72) and in roadside and urban areas (2 of
      21); in controls these prevalences were 3.4% and 9.9%, respectively. The relative
      risk of HIV-1 infection for the development of leprosy was estimated to be 2.2
      [95% confidence interval (CI) = 1.0-4.7; p = 0.07]. HIV-1 infection was
      significantly associated with multibacillary (MB) leprosy (odds ratio 4.6; CI =
      1.3-13.2) but not with paucibacillary leprosy (odds ratio 1.4; 95% CI = 0.4-3.8).
      The population etiological fraction for the development of MB leprosy
      attributable to HIV-1 infection in this population is estimated to be 13% (95% CI
      = 4%-23%). We conclude that HIV-1 is a risk factor for the development of MB
      leprosy. The impact of the HIV-1 epidemic on the incidence of leprosy so far has
      been limited since HIV-1 occurs mainly in urban areas and leprosy in rural areas.

PMID- 8151187
TI  - Sensitization potential and reactogenicity of varying doses of BCG plus killed
      Mycobacterium leprae: an extended study.
AB  - This study is an extension of a previous study on an antileprosy combination
      vaccine of BCG plus killed Mycobacterium leprae (KML) regarding its sensitization
      potential and reactogenicity. The study was extended to see if by reducing the
      dose of BCG in the combination vaccine the incidence of suppurative adenitis
      could be reduced without a significant reduction in the level of postvaccination
      skin-test responses. The study included 860 individuals, and three preparations
      of the combination vaccine [BCG 0.05 mg + 6 x 10(8) KML (I), BCG 0.05 mg + 5 x
      10(7) KML (II), BCG 0.01 mg + 5 x 10(7) KML (III)] along with normal saline
      (i.v.) were used. Each individual received one of these four preparations by
      random allocation. They were also tested with Rees' M. leprae soluble antigen
      (MLSA) and lepromin A 12 weeks after vaccination. Reactions to the MLSA were
      measured after 48 hr; reactions to lepromin A after 48 hr and 3 weeks. The
      character and size of the local response at the vaccination site were recorded at
      the third, eighth, and 15th week postvaccination. The results of the study showed
      that by halving the dose of BCG in the combination vaccine BCG plus 6 x 10(8) KML
      a) the incidence of suppurative regional adenitis was reduced significantly, b)
      there was no significant change in the post-vaccination response at 12 weeks as
      measured by Rees' MLSA and lepromin A, and c) the evolution of the vaccination
      lesion was somewhat prolonged. This dose was found satisfactory for use in a
      comparative antileprosy vaccine trial in South India.

PMID- 8151188
TI  - Serological response in leprosy and tuberculosis patients to the 18-kDa antigen
      of Mycobacterium leprae and antigen 85B of Mycobacterium bovis BCG.
AB  - Two enzyme-linked immunosorbent assays (ELISAs) for the detection of leprosy
      antibodies were developed. These assays were based on the recombinant 18-kDa
      protein of Mycobacterium leprae and the 85B antigen of M. bovis. Sera from
      leprosy and tuberculosis patients were analyzed, and a phenolic glycolipid-I (PGL
      I) ELISA was used as a reference test. The 18-kDa ELISA reached a sensitivity of
      70% on lepromatous leprosy sera. The corresponding results for the 85B and the
      PGL-I ELISAs were 93% and 96%, respectively. The sensitivity on tuberculoid
      leprosy sera was 72% for the 18-kDa antigen, 95% for the 85B antigen, and 60% for
      the PGL-I antigen. The 18-kDa antigen ELISA was found to have crossreactivity to
      sera from patients with tuberculosis, while the 85B and PGL-I assays had high
      specificity.

PMID- 8151189
TI  - Altered calcium-binding ability of plasma proteins as the cause of hypocalcemia
      in lepromatous leprosy.
AB  - This paper reports a study performed on 10 lepromatous leprosy outpatients and on
      the same number of age- and sex-matched contacts. All of the lepromatous patients
      were hypocalcemic, but plasma levels of ionized calcium and the acid-base status
      were normal. The average daily food intake assessed through a questionnaire
      revealed adequate nutrition of patients and controls. Plasma proteins and 1,25
      dihydroxyvitamin D3 and intestinal absorption of calcium were discarded as the
      causes of the hypocalcemia. In vitro experiments designed to investigate the
      effect of hydrogen ion concentration on the equilibrium between calcium ion and
      proteins revealed that, at normal pH values, plasma proteins from lepromatous
      leprosy patients bind a smaller fraction of total plasma calcium than those from
      controls. This phenomenon produces a normal concentration of ionized calcium that
      determines a normal parathyroid status as indicated by the normal urinary
      excretion of hydroxyproline and plasma concentrations of alkaline phosphatase
      (total and bone isoenzyme) and tartrate-resistant acid phosphatase.

PMID- 8151190
TI  - Neuritis of the lateral femoral cutaneous nerve in leprosy.
AB  - Neuritis of the lateral femoral cutaneous nerve (meralgia paresthetica) is
      observed more frequently in leprosy than in nonleprosy patients, and its symptoms
      can easily be confused with those suggesting, e.g., ischialgia. The diagnosis can
      be confirmed by a diagnostic block with a local anesthetic solution. Analgesics,
      antiinflammatory drugs, bed rest and, in severe cases, therapeutic blocks were
      successfully applied in the treatment of the neuritis, and no surgical
      intervention was needed. Three leprosy patients with severe meralgia paresthetica
      are presented.

PMID- 8151191
TI  - Cytological needle aspiration of the nerve for the diagnosis of pure neural
      leprosy.
AB  - Pure neural (also called primary neuritic) leprosy manifests itself by
      involvement of only the nerve in the absence of skin lesions. Therefore, it
      sometimes can pose a diagnostic problem. Cytological needle aspiration of an
      affected nerve can be a valuable tool under such circumstances. The method as
      developed at Anandaban Leprosy Hospital, Nepal, is described and two cases are
      presented.

PMID- 8151193
TI  - Activity of sparfloxacin against Mycobacterium leprae measured by the
      proportional bactericidal test.
AB  - The activity of 25 mg/kg and 50 mg/kg sparfloxacin was measured against
      Mycobacterium leprae in normal (immunocompetent) mouse foot pads by the
      proportional bactericidal test. This was compared with the action of 25, 50, and
      150 mg/kg ofloxacin by the same method. Sparfloxacin, at both concentrations, was
      found to be strongly bactericidal by this method, comparable to 150 mg/kg
      ofloxacin.

PMID- 8151192
TI  - A simple and rapid technique for the detection of rifampin resistance in
      Mycobacterium leprae.
AB  - The rifampin resistance of Mycobacterium leprae is due to missense mutations in
      the rpoB gene encoding the beta-subunit of the essential enzyme RNA polymerase. A
      rapid and very simple method has been developed to detect rifampin resistance in
      small numbers of M. leprae present in biopsies. It involves polymerase chain
      reaction amplification of a defined region of the rpoB gene followed by single
      strand conformational polymorphism analysis (PCR-SSCP). The reliability of the
      method has been tested on a sample of known drug-resistant and susceptible
      isolates of M. leprae.

PMID- 8151194
TI  - Differential production of interleukin 1 (IL-1), IL-6, tumor necrosis factor, and
      IL-1 receptor antagonist by human monocytes stimulated with Mycobacterium leprae
      and M. bovis BCG.
AB  - Human blood monocytes cultured in various serum conditions were stimulated with
      Mycobacterium leprae or M. bovis BCG and their cytokine-inducing abilities were
      compared. BCG, either live or killed, induced production of interleukin 1 (IL-1),
      IL-6, tumor necrosis factor (TNF), and IL-1 receptor antagonist (IL-1ra). Live
      BCG at a lower bacterial number was more potent than killed BCG in the induction
      of IL-6 and TNF. In contrast to BCG, killed M. leprae induced few cytokines
      except for IL-1ra. Similar results were obtained when monocytes were cultured in
      the presence of untreated or heat-inactivated fetal bovine serum (FBS). When FBS
      and human serum (HS) were compared and the effect of heat inactivation was
      investigated, monocytes in HS produced the most cytokines, then those in FBS,
      irrespective of heat inactivation, and those in heat-inactivated HS produced the
      least cytokines. There were no differences between live and killed M. leprae, and
      BCG were far more potent than M. leprae in all of our experimental conditions,
      indicating that the poor cytokine (IL-1, IL-6 and TNF)-inducing ability of M.
      leprae was not due to their viability. Cytokine production was partially in
      parallel with the phagocytosis of the mycobacteria. These results suggest that M.
      leprae favor their infection by evoking little host reaction through the
      induction of only low levels of immunostimulatory or proinflammatory cytokines
      but a substantial amount of immunosuppressive cytokine.

PMID- 8151195
TI  - A singular obsession: New Brunswick's leprosy doctor.

PMID- 8151196
TI  - How effective is monthly rifampin?

PMID- 8151197
TI  - Leprosy--economy--environment; might we predict leprosy incidence from this point
      of view?

PMID- 8151198
TI  - Lack of response to WHO/MDT; a case report.

PMID- 8151199
TI  - An investigation of mast cells in two basic leprosy groups.

PMID- 8151200
TI  - Pedal edema following clofazimine therapy; a case report.

PMID- 8151202
TI  - Members of the International Leprosy Association.

PMID- 8151201
TI  - 1993 Damien-Dutton Award recipient.

PMID- 8151203
TI  - Subject descriptions and single-subject research.
AB  - In this manuscript, we respond to the minimum standards for describing research
      subjects as proposed by the Council for Learning Disabilities (CLD) Research
      Committee. Three issues are raised about the standards: (a) whether justification
      exists for the recommended standards, (b) whether a relationship exists between
      the description of subjects and the probability of replication, and (c) whether
      all types of research require the same subject description standards. These
      issues are discussed, and three recommendations to investigators who use single
      subject research designs are made: (1) Describe variables that control subjects'
      performance in baseline conditions and the contexts of that performance, (2)
      identify subject selection criteria, and (3) report status variables as
      recommended by the CLD Research Committee.

PMID- 8151204
TI  - A postmodern critique of Conte's, Andrews's, Gresham's, and Elliott's
      assumptions.
AB  - In this article I suggest that the assumptions that Conte, Andrews, Gresham, and
      Elliott make regarding the characteristics that should be attributable to
      learning disabilities are limited by the "either/or" empirical view. I contend
      that (a) there is no such phenomenon as a pure primary disorder; all behavioral
      and learning problems are manifested by a discrete cluster of behaviors, so that
      one differentiates exceptionalities by looking at the quality of behaviors and
      possible antecedents rather than comparing them quantitatively; (b) that learning
      disabilities are earmarked by the inefficient manner in which tasks are
      approached in one's specific area(s) of deficient intellect rather than by
      universal characteristics; (c) that all aspects of learning are metaphorical and,
      therefore, have implicit dimensions; and learning disabilities are, in large
      part, a deficit in learning implicit information; (d) that in-school and out-of
      school learning are of a piece and must be synthesized, just as theory, research,
      and practice must be synthesized; and (e) that the definition should not dictate
      our notion of what learning disabilities are, but rather should reflect our
      observations of persons with learning disabilities.

PMID- 8151205
TI  - Nonverbal learning disabilities and socioemotional functioning: a review of
      recent literature.
AB  - Over the past decade, there has been increasing interest in the use of subtyping
      techniques for research and treatment of learning disabilities (LD). This article
      presents an overview of the current literature relating to a nonverbal learning
      disabilities (NLD) subtype. Research on the relationship between nonverbal
      learning disabilities and socioemotional functioning is critically reviewed.
      Issues of generalizability of research outcomes, individual differences, and
      treatment validity are addressed. Emphasis is on findings that are most likely to
      have direct relevance for practitioners.

PMID- 8151206
TI  - Parallels between math and reading disability: common issues and approaches.
AB  - There is a relatively larger body of research on reading than on math
      disabilities. However, many research findings and theoretical issues are common
      to both areas of study. In this review, similarities in skill acquisition across
      domains are identified, and findings concerning the nature of the differences
      between learners with and without disabilities are discussed. Evaluating the
      areas of similarity and difference between reading and math disabilities may
      enhance our understanding of individual differences in learning abilities, and
      may be useful in guiding future research and theory development.

PMID- 8151207
TI  - A comparison of fast-rate, slow-rate, and silent previewing interventions on
      reading performance.
AB  - Researchers investigated the effects of three different previewing interventions
      on the oral reading rates of 12 junior and senior high school students with
      learning disabilities. Under fast-rate listening previewing (FRLP), students were
      instructed to follow silently as experimenters read from a text at an average
      rate that was 77.7% faster than the students' current oral reading rate. During
      slow-rate listening previewing (SRLP), students followed along as experimenters
      read at an average rate that was 22.5% faster than the students' reading rate.
      Students were instructed to read passages silently under silent previewing (SP).
      Immediately following each previewing intervention, students read the same
      passage aloud. The number of words read correctly per minute and the number of
      errors per minute served as dependent variables. The results showed statistically
      significant decreases in error rates under SRLP and SP. The results also showed
      that SRLP resulted in statistically significantly fewer errors per minute than
      FRLP. These results suggest that orally reading while students follow along at a
      rate much higher than their current reading rates may not be as beneficial as
      reading aloud at slower rates.

PMID- 8151208
TI  - Eye-movement rhythmicity and reading comprehension.
AB  - The purpose of these two studies was to examine the rhythmical patterns displayed
      by subjects with and without reading disabilities while they were reading (Study
      1), and to vary rhythmicity through priming and observe the effects on parsing
      ability using eye-movement and comprehension measures (Study 2). Rhythmicity
      during silent reading was operationalized by transcribing eye-movement measures
      into pitch, rhythm, and rests. In Study 1, 17 subjects with reading disabilities
      and 15 control subjects (M age = 15, male = 60%) parsed 20 flawed and control
      sentences. In Study 2, 35 control subjects (M age = 21, male = 43%) parsed 9
      phrases from familiar songs under one of three rhythm-priming conditions. Results
      (Study 1) indicated significant differences in rhythm patterns. Subjects with
      reading disabilities exhibited rhythm variability, unpredictability, and
      lethargic tempos. In Study 2, significant differences across priming conditions
      were found, with primed subjects exhibiting improved parsing and comprehension.
      Rhythm may be an organizational substrate for syntax.

PMID- 8151209
TI  - A longitudinal study on dysgraphic handwriting in primary school.
AB  - In an epidemiological study, the scripts of 121 Dutch primary-school children
      were evaluated annually, starting in Grade 2. The children were followed for 5
      years. An evaluation scale for children's handwriting (the BHK scale) was used
      for rating the scripts on 13 characteristics and for measuring the speed of
      writing. Principal component analysis of the LONG matrix (in which the data
      collected on the five occasions are arranged beneath each other) yielded three
      clusters of items: (a) fine-motor ability, (b) structural performance, and (c)
      stylistic preference. It was found that the children with dysgraphic handwriting
      (10% scoring highest on the BHK quality items) had lower fine-motor ability and,
      in the higher grades, showed less preference for a personal style. Their
      structural performance also was poorer than that of the other writers. Children
      with and without dysgraphic handwriting did not differ in writing speed. Some
      implications of the study for handwriting instruction are discussed.

PMID- 8151210
TI  - Child abuse and neglect: an overview.

PMID- 8151211
TI  - Child abuse and neglect: the need for education.

PMID- 8151212
TI  - Reporting child abuse and neglect.

PMID- 8151213
TI  - Case studies. Child abuse.

PMID- 8151214
TI  - The dentist's role in treating child abuse.

PMID- 8151215
TI  - Can a dentist be charged with child abuse?

PMID- 8151216
TI  - Abuse of disabled persons.

PMID- 8151217
TI  - Dentistry and family violence.

PMID- 8151218
TI  - Elder abuse.

PMID- 8151219
TI  - A clinico-pathologic presentation. Hyperostosis.

PMID- 8151220
TI  - A clinico-pathologic presentation. Geographic tongue.

PMID- 8151221
TI  - Questions and answers about managed competition.

PMID- 8151222
TI  - Infectious diseases in dentistry: answers to ten legal (or illegal?) questions.

PMID- 8151223
TI  - Gloves: are they safe and effective?

PMID- 8151224
TI  - A case of a central odontogenic fibroma presenting a differential diagnostic
      problem.
AB  - Central odontogenic fibromas are rare benign tumors. We are presenting a case of
      a 67-year-old female with a central odontogenic fibroma which posed considerable
      difficulty in microscopic interpretation. The differential diagnosis ranged from
      metastatic carcinoma to a benign odontogenic neoplasm. The final diagnosis was
      made through persisting on multiple pathologic consultations, which allowed for
      conservative rather than aggressive surgery. Follow-up evaluation has confirmed
      the benign diagnosis.

PMID- 8151225
TI  - On Clinton's health care reform proposal, further reflections.

PMID- 8151227
TI  - Deja vu all over again: the health insurance reform debate in Georgia.

PMID- 8151226
TI  - What's going on ... at the Capitol?

PMID- 8151228
TI  - True managed competition versus the Clinton health plan. Why the real thing is
      better than "gumbo soup".

PMID- 8151229
TI  - Physicians prescription for Georgia, building a better state of health: a
      synopsis.

PMID- 8151230
TI  - Doctor's watch: how to avoid lab fines.

PMID- 8151231
TI  - Understanding participating physician agreements.

PMID- 8151232
TI  - Guns and self-protection.

PMID- 8151233
TI  - Eddies in the stream: of our family and our priorities.

PMID- 8151234
TI  - Physicians for patient power.

PMID- 8151235
TI  - After the fall: particularism in bioethics.

PMID- 8151236
TI  - A qualified bioethic: particularity in James Gustafson and Stanley Hauerwas.
AB  - Most theoretical approaches in bioethics begin with a theory that articulates and
      defends basic principles or rules that are more or less systematically related
      and that seek to yield more or less precise conclusions with regard to specific
      acts, cases, or policies. Concerns about the agent and descriptions of the
      context of action stand on the margins of the theory. This is ironic, given the
      overwhelming importance and impact the training of health care professionals has
      upon them and upon the practice of health care as a whole, and given the fact
      that many advocates of the theories themselves concede that one's beliefs and how
      one describes a situation and weighs "facts" and values relevant to the case
      strongly determine one's conclusions. While morality may not lead ineluctably to
      religion, as Kant believed, bioethics does appear inevitably to involve
      particularity. I examine the work of James M. Gustafson and Stanley Hauerwas to
      analyze two views of the role of particularity in bioethics. I then show the
      relevance of their work for addressing some problems with the practicality and
      concreteness of current models in bioethics.

PMID- 8151237
TI  - An Eastern Orthodox approach to bioethics.
AB  - This article seeks to identify some of the major perspectives in Eastern Orthodox
      Christianity which provide direction for bioethical-decision making. The article
      first identifies some historical, theological, and liturgical sources in the
      Eastern Orthodox tradition which have implications for bioethics. The manuscript
      also seeks to address the question of the place of religious bioethics within
      public discussion of issues in bioethics and health care policy.

PMID- 8151238
TI  - Talking ethics with strangers: a view from Jewish tradition.
AB  - The work of H. Tristram Engelhardt provides an important set of reflections for
      bioethics in a secular context. Taking Engelhardt's work as its point of
      departure this article explores the challenges that Jewish ethicists face in
      contributing to bioethics in a secular context. The article explores how the
      Jewish tradition can address issues in bioethics in ways that are true to its
      tradition and at the same time accessible and relevant to "moral strangers" in a
      secular society.

PMID- 8151239
TI  - The common good in a secular society: the relevance of a Roman Catholic notion to
      the healthcare allocation debate.
AB  - This essay analyzes Roman Catholic social teaching on the right to health care
      and the legitimacy of healthcare rationing. It considers that discussion at two
      levels: (1) the specific warrants that undergrid key terms; and (2) the
      accessibility and applicability of those warrants to policy choices in a secular
      society. The essay concludes with a number of broader reflections meant to
      reserve an appropriate place for religious voices in the process of policy
      making, as distinguished from its justification.

PMID- 8151240
TI  - Sealing ability of a mineral trioxide aggregate for repair of lateral root
      perforations.
AB  - Amalgam, IRM, and a mineral trioxide aggregate were tested for repair of
      experimentally created root perforations. Fifty sound, extracted mandibular and
      maxillary molars were used in this study. A perforation was created on the mesial
      root surface at about a 45-degree angle to the long axis of each tooth. The tooth
      was then placed into a saline-soaked "Oasis" to simulate a clinical condition.
      After placing the repair materials into the perforations, the teeth were kept for
      4 wk in the Oasis model. The perforation sites were then stained with methylene
      blue for 48 h, sectioned, and examined under a dissecting microscope. The results
      showed that the mineral trioxide aggregate had significantly less leakage than
      IRM or amalgam (p < 0.05). The mineral trioxide aggregate also showed the least
      overfilling tendency while IRM showed the least underfilling tendency.

PMID- 8151241
TI  - In vivo measurement accuracy in vital and necrotic canals with the Endex apex
      locator.
AB  - Currently apex locators are being used to determine working length. This study
      was undertaken to see what is actually being measured and if the pulp status,
      i.e. vital or necrotic, makes a difference in the determination. In this in vivo
      study, 33 teeth, both vital and necrotic, were measured by the Endex apex locator
      and then radiographed. After the length determination, the file was cemented to
      place, the tooth extracted, and then shaved back until the file and the apex were
      exposed. The position of the file was measured in relation to the apical foramen.
      Results indicate that all measurements were within a narrow range (-0.86 mm to
      0.50 mm). There was no statistical difference in measurements between vital and
      necrotic canals.

PMID- 8151242
TI  - A novel noninstrumented technique for cleansing the root canal system.
AB  - The aim of this study was to develop a machine to clean root canals without
      conventional instruments. This goal was achieved with a device which was able to
      develop controlled cavitation in the root canal. Under reduced pressure,
      alternating pressure fields generated microscopic and macroscopic cavitation
      bubbles. Subsequently, these vapor-filled cavitation bubbles collapsed, creating
      hydrodynamic turbulence. These two phenomena allowed the irrigant to penetrate
      the canal system and then be exchanged with new irrigant. To test the cleaning
      ability of the device 79 freshly extracted vital molars with 222 root canals were
      collected. The control group (27 molars, 73 canals) was prepared with the step
      back technique using NaOCl (3%) as an irrigant. The three test groups (52 molars,
      149 canals) were prepared with the new machine using NaOCl (1, 2, or 3%). The
      treatment time ranged from 16 to 32 min in the hand group and from 10 to 15 min
      in the machine groups. The teeth were then prepared histologically and examined
      by light microscopy. Overall, the treatment with NaOCl (2 and 3%) resulted in
      similar or better cleanliness in all three root sections when comparing machine
      and hand instrumentation. In curved canals, however, the apical one third was
      also significantly cleaner when using the machine and 3% NaOCl than with hand
      instrumentation. This in vitro study shows that it is possible to clean a root
      canal system by a noninstrumented technique as well as by conventional hand
      instrumentation.

PMID- 8151243
TI  - Reduced cytotoxicity of a root canal sealer through eugenol substitution.
AB  - The cytotoxicity of two zinc oxide root canal sealers was investigated in vitro.
      The sealers were freshly mixed and set for 24 and 168 h. The sealers had
      identical powders but different liquid components. One (Canals) used eugenol,
      while the other (Canals-N) used fatty acids. L929 cells were incubated for 4 and
      24 h in direct contact with the materials or with an eluate of the materials. The
      toxicity was evaluated using the radiochromium release assay. In the direct
      exposure assay, both sealers were cytotoxic when freshly prepared or after 24 h
      of setting. After 1 wk of setting, Canals was still toxic, while Canals-N was not
      significantly different from the control in the 4-h assay. In the elution assay
      the materials showed very low cytotoxicity. Only the eluate from freshly prepared
      Canals was clearly cytotoxic after 24 h. The liquid of Canals-N was clearly less
      cytotoxic than liquid from Canals. The results showed that the cytotoxicity of a
      root canal sealer can be reduced by replacing eugenol with fatty acids.

PMID- 8151244
TI  - Dentinal wall adaptation of thermoplasticized gutta-percha in the absence or
      presence of smear layer: a scanning electron microscopic study.
AB  - The dentinal adaptation of injected thermoplasticized gutta-percha and
      thermoplasticized gutta-percha resulting from Ultrafil and Thermafil systems was
      evaluated by scanning electron microscopy and compared with adaptation obtained
      with the lateral condensation of gutta-percha. Each method was evaluated with and
      without the smear layer removed. Scanning electron microscopic observations
      showed the thermoplasticized gutta-percha resulting from either system to have
      better dentinal wall adaptation than lateral condensation of gutta-percha in
      either the absence or presence of the smear layer. In the absence of smear layer,
      the adaptation of gutta-percha was improved in all groups. Although sealer was
      used, removing the smear layer was found to enhance the ability of the
      thermoplasticized gutta-percha to enter the patent tubules.

PMID- 8151245
TI  - Thermafil retreatment with and without chloroform solvent.
AB  - A previous study reported that retreatment of Thermafil-obturated canals resulted
      in significantly more remaining gutta-percha than retreatment of those obturated
      with laterally condensed gutta-percha. The purpose of this study was to evaluate
      two retreatment methods in Thermafil-obturated canals. Thirty canals were cleaned
      and shaped. They were obturated with Thermafil and sealer. One-half were
      retreated using chloroform to aid in gutta-percha removal (group 1). The others
      were retreated without chloroform (group 2). The ease or difficulty of removing
      the metal carrier was assessed during each retreatment. The teeth were split
      longitudinally; the canal area and remaining gutta-percha area were measured in
      the coronal, middle, and apical thirds. The results were analyzed by analysis of
      variance. In each group, seven Thermafil devices were easy to remove and eight
      were difficult. No significant differences were found in comparing the two
      groups. However, when the factor of ease of removal was added there were
      significant differences. Group 2 had significantly less gutta-percha in the
      apical third (5.9%) when the device was easily removed than when it was hard to
      remove (54.2%). Group 2 canals were significantly cleaner in the apical third
      than group 1 canals whether the device was difficult (38.3%) or easy to remove
      (42.5%). Adequacy of Thermafil retreatment may be related more to the ability to
      easily remove the carrier than to the technique of gutta-percha removal.

PMID- 8151246
TI  - Role of catalase in the elimination of residual hydrogen peroxide following tooth
      bleaching.
AB  - Hydrogen peroxide at high concentrations may cause damage to the tooth structure
      and to the surrounding periodontal tissues. The efficacy of catalase applied
      following intracoronal bleaching to eliminate residual hydrogen peroxide was
      examined and compared with prolonged water rinses. Extracted human premolars were
      treated endodontically and bleached with 30% hydrogen peroxide. Upon completion
      of the bleaching procedure, the teeth were treated with either catalase or water.
      Radicular hydrogen peroxide penetration was measured immediately after bleaching
      and following each catalase and/or water rinse. A correlation between the number
      of water rinses and the reduction in the radicular hydrogen peroxide penetration
      was found. Three cycles of 5-min water rinses and 1-h immersion of the teeth in
      water significantly reduced the residual hydrogen peroxide penetration. One
      treatment with catalase applied for 3 min totally eliminated the residual
      hydrogen peroxide. It is therefore suggested that catalase be used as an adjunct
      following intracoronal bleaching of nonvital teeth to effectively eliminate the
      residual hydrogen peroxide from the pulp chamber and from the surrounding
      periodontal tissues.

PMID- 8151247
TI  - An experimental study of the sealing ability of a dentinal apical plug treated
      with bonding agent.
AB  - The purpose of this study was to evaluate the sealing ability of a dentinal
      apical plug treated with a bonding agent. Ninety human lower premolars were used.
      The teeth were divided into three groups. in groups 1 and 2, to prepare an apical
      isthmus of 1 mm in length, the first apical seat was prepared with a #45 K file 1
      mm short of the anatomical apex and with a #60 K file 2 mm short for the second
      apical seat. Dry dentin fillings were packed in the apical isthmus with a #60 K
      file. In group 1, the root canal was obturated with gutta-percha and Canals root
      canal sealer by the lateral condensation method. In group 2, following an
      application of the bonding agent to the plug, the root canal was obturated in the
      same way. In group 3 (control), a single apical seat was prepared with a #60 K
      file 1 mm short of the apex and the root canal was obturated similarly. The teeth
      of three groups were immersed in a 1% methylene blue solution for 1, 2, and 4 wk.
      Dye penetration depth from the apical foramen was determined. Group 2 showed no
      leakage after 4 wk. Groups 1 and 3 showed dye penetration into the root canal,
      and in these two groups dye penetration increased with time.

PMID- 8151248
TI  - Factors associated with endodontic posttreatment pain.
AB  - One hundred six patients with pretreatment pain presenting for endodontic
      treatment participated in a controlled double-blind study of dexamethasone use.
      Endodontic therapy was performed and, after controlling for use of nonuse of
      dexamethasone, patient variables and treatment factors were evaluated for their
      effects on endodontic posttreatment pain. Patients with no radiographic
      periapical lesions had significantly more pain than patients with periapical
      lesions at 8-, 24-, 48-, and 72-h posttreatment regardless of whether they
      received placebo or dexamethasone. No other patient or treatment factors
      correlated with posttreatment pain. Twenty-two patients in the subgroup receiving
      placebo reported an 81% incidence of posttreatment pain, 73% of them required
      posttreatment pain medications. By 72-h posttreatment, the incidence and severity
      of pain in the placebo group was minimal.

PMID- 8151249
TI  - Root invagination treatment: a conservative approach in endodontics.
AB  - The occurrence of dens invaginatus, a developmental anomaly, is reported to be
      0.04 to 10%. Treatment modalities, such as extraction, endodontic surgery, and
      conventional instrumentation of the defect and/or the pulp canal, have been
      reported. Most suggested treatment modalities are based on the assumption that
      the tissue inside the invagination communicates with the pulp tissue. However,
      histological studies show that depending on the type of invagination, the
      entrapped tissue is mostly connective tissue which may or may not contain pulp
      tissue components. In situations where the invaginated tissue is contaminated and
      yet no communication with the pulp cavity exists, it is possible to instrument
      and disinfect the invagination without affecting the pulp and sacrificing tooth
      vitality. Such treatment will be referred to as "root invagination treatment." A
      case is described where tooth vitality was preserved when only the invagination
      was treated.

PMID- 8151250
TI  - A simplified model to demonstrate the operation of electronic root canal
      measuring devices.
AB  - This article describes how to construct and use a simplified model to demonstrate
      the operation of electronic root canal measuring devices. The model is effective,
      more economical than those previously described, and uses readily available
      materials.

PMID- 8151251
TI  - Long-term sealing efficacy of four root surface sealing materials used in
      endodontic leakage studies.
AB  - Fifty extracted human maxillary anterior teeth were biomechanically instrumented
      and divided into five equal groups, four experimental and a control. The teeth in
      the experimental groups had their root surface coated with one of four sealants;
      epoxy, casting resin, sticky wax, or nail polish. The roots of the remaining
      teeth were not coated and served as controls. All of the teeth were mounted in
      the caps of scintillation vials. Five microliters of [3H]uridine were deposited
      in the root canal space and disintegration counts were obtained over time periods
      of 1, 4, 8, 12, and 36 wk. At the conclusion of the experiment, sticky wax was
      demonstrated to provide a superior seal (p < 0.0001).

PMID- 8151252
TI  - Sealing ability of a mineral trioxide aggregate when used as a root end filling
      material.
AB  - This in vitro study used rhodamine B fluorescent dye and a confocal microscope to
      evaluate the sealing ability of amalgam, super EBA, and a mineral trioxide
      aggregate when used as root end filling materials. Thirty single-canal teeth were
      cleaned, shaped, and obturated with gutta-percha and root canal sealer. After
      application of nail polish to the external surface, the apical 3 mm of each root
      was resected and 3-mm deep root end preparations were made. The roots were
      randomly divided into three groups and the root end preparations filled with the
      experimental materials. All roots were then exposed to an aqueous solution of
      rhodamine B fluorescent dye for 24 h, longitudinally sectioned, and the extent of
      dye penetration measured using a confocal microscope. Statistical analysis showed
      that the mineral trioxide aggregate leaked significantly less than amalgam and
      super EBA.

PMID- 8151253
TI  - AH 26 releases formaldehyde.

PMID- 8151254
TI  - Evaluation of sealing properties of Thermafil and Ultrafil techniques in the
      absence or presence of smear layer.
AB  - The apical sealing abilities of two thermoplasticized gutta-percha techniques
      were evaluated. A total of 128 single-rooted teeth were divided into six groups
      in which Ultrafil, Thermafil, and lateral condensation techniques, with and
      without the smear layer, were used to obturate 20 roots in each group. The roots
      were implanted subcutaneously in rats for 90 days to expose the materials to
      vital tissue and tissue fluids. The roots were recovered, immersed in 1%
      methylene blue for 2 wk, cleared, and the dye penetration was measured using a
      dissecting microscope. Thermafil showed the least leakage with smear layer
      present and Ultrafil the least with it absent. The two thermoplasticized gutta
      percha techniques both showed significantly less leakage than lateral
      condensation with and without the smear layer. Removing the smear layer reduced
      the leakage significantly in all groups.

PMID- 8151255
TI  - Computerized three-dimensional reconstruction: a method to study pulpal vessels
      and nerves.
AB  - This study describes a method of computerized three-dimensional reconstruction of
      the main neurovascular pulpal bundle of human teeth, using serial cross paraffin
      sections, digital image processing, and three-dimensional computer graphics.

PMID- 8151256
TI  - Comparison of endodontic retreatment of laterally condensed gutta-percha and
      Thermafil with plastic carriers.
AB  - The purpose of this study was to evaluate canal wall cleanliness in cases of
      retreatment using laterally condensed gutta-percha and Thermafil with plastic
      carriers. Forty extracted mandibular canines were prepared using a step-back
      flared technique and divided into two groups: group A, obturated with lateral
      condensation and group B, obturated with Thermafil. AH26 was the sealer used in
      both groups. Retreatment of all teeth was done using Gates Glidden burs and a
      solvent. The teeth were then split longitudinally, photographed, and projected
      onto a screen at x10 magnification. The total area of the canal and the area of
      gutta-percha/sealer were then traced on white paper. Both areas were accurately
      quantified using a computerized image analysis system and the ratio of remaining
      obturation material to root canal periphery was derived and statistically
      analyzed. Results showed that the average percentage of the remaining gutta
      percha/sealer was 14.23 for the lateral condensation group and 15.70 for the
      Thermafil group with no statistically significant difference (Student's t test, p
      = 0.01). The plastic carrier was easily removed from the canals.

PMID- 8151258
TI  - Vital root canal treatment of a dens in dente.
AB  - A case of dens invaginatus is presented in which a greatly enlarged mandibular
      lateral incisor radiographically appeared to have a tooth within a tooth (dens in
      dente). The dens was treated endodontically without violating the integrity of
      the pulp.

PMID- 8151257
TI  - Dental pain: self-observations by a neurophysiologist.
AB  - This is a description of a dentally trained neurophysiologist's first-hand
      experience of the slow and progressive deterioration of the pulp of one of his
      posterior teeth. He describes his sensations throughout the course of the pulpal
      pathosis and his experience as a patient undergoing endodontic treatment for the
      first time. His subjective experiences are put into the context of the current
      understanding of the physiology of pain.

PMID- 8151259
TI  - Pseudocyst of the maxillary sinus.
AB  - A case report is presented involving the endodontic retreatment of a maxillary
      second molar associated with a sinus radiopacity. Disappearance of sinus pathosis
      occurred within 6 days after root canal debridement. A direct relationship
      between apical pathosis and a pseudocyst of the maxillary sinus is suggested.
      Thirteen-month recall shows no recurrence.

PMID- 8151260
TI  - The treatment of chronic myeloid leukaemia--much still to be achieved.

PMID- 8151261
TI  - The lamentable state of basic patient-oriented research: a call for action.

PMID- 8151262
TI  - Systemic blood pressure and glomerular leakage with particular reference to
      diabetes and hypertension.
AB  - Both day and night blood pressure have considerable ranges in normal individuals
      and also in diabetic patients. In addition, there is considerable variation intra
      individually, with considerable excurses in blood pressure, e.g. during exercise,
      other daily activities as well as on exposure to medical personnel. There is good
      evidence to suggest that elevated blood pressure is an important factor in the
      progression of renal disease in diabetes, even from the initial phase of the
      slight elevation of the albumin excretion rate. From the earliest phase of
      microalbuminuria, blood pressure may increase by an average of 3-4 mmHg per year
      in contrast to 1 mmHg per year in healthy controls and in clearly
      normoalbuminuric individuals. Throughout the course of the complications of
      diabetes, both insulin-dependent and non-insulin-dependent, there is a
      correlation between albuminuria and blood pressure in cross-sectional studies;
      also there is a significant correlation between blood pressure and the
      progression of albuminuria. The same findings are available in essential
      hypertension and also to some extent in the background population, although in
      the latter the correlation between albuminuria and blood pressure is much less
      precise, although highly significant. Several trials conducted over the years
      uniformly show that antihypertensive treatment reduces albuminuria and, in many
      studies, progression in renal disease also, as measured by the glomerular
      filtration rate (GFR) fall. Therefore, it could be considered as a means to
      reduce blood pressure generally in diabetic individuals, even from the start of
      diabetes, with the aim of future further prevention of renal complications and
      possibly other complications. Such a proposal is less attractive in the
      background population because renal disease is much more rare. Another similar
      approach would be the prevention of renal disease, e.g. diabetics. Obviously,
      abnormalities in the vascular wall of a biochemical/functional nature may make
      diabetics more pressure-sensitive, and the indication is that several other risk
      factors are involved, in particular poor metabolic control. Nevertheless, it is
      proposed that trials should be conducted very early in the course of diabetes, to
      see if the same positive effect can be obtained early as that documented later in
      the course of microalbuminaria and overt renal disease, both in insulin-dependent
      and in non-insulin-dependent diabetes. In essential hypertension,
      antihypertensive treatment has a profound effect on albuminuria, and this may be
      associated with long-term renoprotection, but this is less well documented.

PMID- 8151263
TI  - Endothelial nitric oxide and cardiovascular disease.
AB  - The vascular endothelium is the site of formation of several powerful mediators.
      One of these is NO, a chemically unstable radical formed by enzymatic conversion
      of L-arginine in the presence of molecular oxygen. NO elicits relaxation of VSMC
      by activating cytosolic guanylate cyclase. NO also counteracts platelet adhesion
      and aggregation. The biological actions of NO make it a key substance in the
      endogenous defense against vascular occlusion and thrombosis. The basal formation
      of NO maintains a moderate but significant vasodilation in the systemic
      resistance vessels and counteracts platelet activity. When blood flow in conduit
      arteries is increased there is an augmented endothelial formation of NO,
      eliciting flow-dependent vasodilation. Beside this, several vasodilators
      (acetylcholine, bradykinin, histamine, substance P) operate by stimulating
      endothelial NO formation. On the other hand, drugs like nitroglycerin and
      papaverine operate independently of the vascular endothelium. Vasodilator
      mechanisms, physiological as well as pharmacological, may therefore be
      characterized as endothelium-dependent (i.e. NO-mediated), or endothelium
      independent (i.e. not mediated by NO). Physiologically, mixed mechanisms occur.
      Failure of the vascular endothelium to elicit NO-mediated vasodilatation may be
      due to decreased formation, increased degradation, decreased sensitivity to the
      NO formed, or a mixture of these factors. Irrespective of the mechanism behind,
      this is referred to as endothelial dysfunction. Endothelial dysfunction occurs in
      several cardiovascular settings, like atherosclerosis, hypercholesterolaemia,
      diabetes, and essential hypertension. Endothelial dysfunction leads to an
      impaired tissue perfusion, increased local vascular resistance, decreased defense
      against thrombus formation, and possibly also decreased defense against
      hypertrophy of the VSMC in the vessel wall media. In patients with CHD,
      endothelial dysfunction leads to an impaired coronary flow response to physical
      and mental stress, and to promotion of platelet adherence and aggregability.
      Endothelial dysfunction is thereby a probable aggravating factor in the
      atherosclerotic process, adding a functional component on top of the structural
      lesions characterizing this disease. A particular form of endothelial
      dysfunction, limited to the arterial resistance vessels, may explain the symptoms
      and clinical characteristics of microvascular angina. In patients with essential
      hypertension, endothelial dysfunction prevails, adding a functional component to
      the structural factors also in this disease. Hitherto, the only therapeutic tools
      available to restore endothelial dysfunction appear to be restriction of the
      dietary intake of lipids, possibly reinforced with intake of antioxidants like
      fish oil and vitamin E. However, large clinical trials to confirm the efficacy of
      such therapy in reversing endothelial dysfunction have not been conducted. In the
      future, more directly acting therapeutic regimens, aimed at supporting or
      substituting the endogenous formation of NO, are likely to appear as well.

PMID- 8151264
TI  - Continuous infusion of furosemide in the treatment of patients with congestive
      heart failure and diuretic resistance.
AB  - OBJECTIVES: To assess the value of treatment with continuous intravenous infusion
      of furosemide (F) in patients with refractory congestive heart failure. DESIGN:
      Open uncontrolled dose-response study. SUBJECTS: Patients with congestive heart
      failure (those with New York Heart Association (NYHA) classes III and IV with an
      assessed amount of oedema of more than 5 kg and diuretic resistance were included
      [n = 10]). Diuretic resistance was defined as: failure to lose weight and/or
      inappropriate urinary sodium excretion (50 mmol 24 h-1) despite bed rest for a
      period of 2-3 days, salt and water restriction, orally and intravenously
      administered furosemide in a dose of 250 mg day-1, digoxin, and when possible an
      ACE inhibitor. Included patients were treated with continuous F infusion at a
      delivery rate of 20 mg-1 over 24 h. The infusion rate was gradually heightened up
      to a maximum dose of 160 mg h-1. MAIN OUTCOME MEASURES: Daily physical
      examination, history of side-effects, determination of serum electrolytes and 24
      h electrolyte excretion during treatment with furosemide. RESULTS: Weight loss
      (mean +/- SD; 12.5 +/- 5 kg) and relief of symptoms was achieved in all patients.
      Mean (+/- SD) 24-h sodium output rose from 19 +/- 16 mmol 24 h-1 (n = 10) on oral
      therapy with 250 mg F to 137 +/- 85 mmol 24 h-1 (n = 8) during 80 mg h-1 and to
      268 +/- 124 mmol 24 h-1 (n = 3) on the maximal dose of 160 mg h-1. CONCLUSION:
      Continuous infusion of F under careful monitoring of the patient is a safe,
      controllable and efficient treatment in patients with severe congestive heart
      failure and diuretic resistance.

PMID- 8151265
TI  - Metformin and metoprolol CR treatment in non-obese men.
AB  - OBJECTIVE: To study the effect of metformin and metoprolol CR on insulin
      sensitivity, blood lipids, fibrinolytic activity and blood pressure. DESIGN: A
      double-blind, placebo controlled, triple cross-over study with randomization to
      either metformin, 850 mg b.i.d., or metoprolol CR 100 mg o.d., or placebo for a
      period of 18 weeks. The glucose uptake was measured with the euglycaemic clamp
      technique after every 6 weeks' treatment period. Blood pressure and blood samples
      were taken every 3rd week. SUBJECTS: Eighteen non-obese men (53 +/- 6 years of
      age). RESULTS: Metformin decreased C-peptide (P < 0.02), FFA (P < 0.003), total
      and low-density lipoprotein cholesterol, tissue plasminogen activator antigen and
      the urinary potassium excretion (P < 0.05 for all), but not blood pressure
      compared to placebo. Metoprolol CR reduced diastolic blood pressure and pulse
      rate; fasting free fatty acids and the urinary potassium increased (P < 0.05 for
      all). No effect of metformin or metoprolol CR was seen on the glucose disposal
      rate, blood glucose, plasma insulin, triglycerides, high-density lipoprotein
      cholesterol, lipoprotein(a), uric acid or plasminogen activator inhibitor 1
      activity or antigen. The glucose uptake was not particularly decreased in these
      subjects. CONCLUSION: The study shows that metformin has some favourable effects
      on metabolism and that metoprolol CR is fairly neutral in this regard. The lack
      of effect of metformin on glucose disposal rate and blood pressure can be
      explained by the fact that the individuals studied were neither insulin resistant
      nor hypertensive. The data does not preclude an antihypertensive effect by
      treating a concomitant insulin resistance.

PMID- 8151266
TI  - The changes in blood pressure after acute stroke: abolishing the 'white coat
      effect' with 24-h ambulatory monitoring.
AB  - OBJECTIVES: To assess the changes in 24-h and casual blood pressure (BP) levels
      following hospitalization for acute stroke. DESIGN: Prospective study of patients
      admitted with acute hemispheric stroke and hospitalized controls using casual and
      24-h BP monitoring. SETTING: Medical wards in a large teaching hospital.
      SUBJECTS: Thirty-three patients (median age 77 years, 17 male) and 21 control
      subjects admitted non-acutely. INTERVENTIONS: All subjects underwent 24-h BP
      monitoring within 24 h of stroke onset (patients) or admission (controls) and
      again at 1 week. Casual BPs were recorded over the same period. MAIN OUTCOME
      MEASURES: The change in BP over the first week in each group. Eleven stroke
      subjects had 24-h BP monitoring repeated at 6 months. RESULTS: In the stroke
      group, 24-h systolic BP (SBP) fell by 7 mmHg (95% CI, 0 to 14 mmHg; P < 0.05) and
      diastolic BP (DBP) by 3 mmHg (95% CI, 0 to 6 mmHg; P < 0.02) over the first week.
      Mean 24-h BP levels in the control group did not change during this period.
      However, casual BP recordings fell in both stroke (18/12 mmHg) and control (19/9
      mmHg) groups. Stroke subjects followed to 6 months showed no further change in 24
      h BP (day 7: 137 +/- 17/79 +/- 13 mmHg; month 6: 138 +/- 16/78 +/- 11 mmHg).
      CONCLUSIONS: Although there was a large fall in causal BPs seen in both groups
      there was only a small, but a significant fall in mean 24-h BP over the first
      week following hemispheric stroke that was not seen in control subjects. Although
      the 'white coat effect' and admission to hospital play an important part in the
      high casual BP observed in the days following acute stroke they are unlikely to
      be the sole factors.

PMID- 8151267
TI  - Relation of maternal blood pressure during pregnancy to birth weight and blood
      pressure in children. The Hypertension in Pregnancy Offspring Study.
AB  - OBJECTIVE: To evaluate the importance of perinatal factors, e.g. low birth
      weight, reduced gestational period and elevated maternal blood pressure during
      pregnancy, as well as high maternal blood pressure at follow-up 7-12 years after
      pregnancy, on blood pressure in children born after normotensive and hypertensive
      pregnancies. DESIGN: Follow-up study in children from hypertensive pregnancies
      and a control group of children born after normotensive pregnancies. SETTING:
      University Hospital, Goteborg, Sweden. SUBJECTS: Thirty-six children born after
      hypertensive pregnancies and a control group of 17 children born after
      normotensive pregnancies were studied at a mean age of 12.5 years. MAIN OUTCOME
      MEASURE: Blood pressure. RESULTS: Systolic blood pressure was higher in children
      born after hypertensive pregnancies. They also had lower birth weight and a
      shorter gestational period. There was a negative correlation between the highest
      recorded maternal blood pressure during pregnancy and birth weight of the child
      and a positive correlation between maternal blood pressure and blood pressure in
      their offspring. No correlation was found between birth weight and blood pressure
      in these children. CONCLUSIONS: Children born after hypertensive pregnancies have
      higher blood pressure compared to children born after normotensive pregnancies.
      There is a positive relationship between childhood blood pressure and maternal
      blood pressure during pregnancy.

PMID- 8151268
TI  - A 5-year follow-up study on the incidence of retinopathy in type 1 diabetes
      mellitus in relation to medical risk indicators.
AB  - OBJECTIVES: The aim of the present study was to describe the 5-year incidence of
      retinopathy in type 1 diabetes mellitus and to characterize risk indicators for
      the development and progression of retinopathy. DESIGN: A cross-sectional study
      of type 1 diabetic patients taken care of at a medical department. SETTING: All
      type 1 diabetic patients attending the Department of Internal Medicine,
      University Hospital, Lund, during a 2-year period were offered ophthalmological
      examination. SUBJECTS: A total of 396 out of 461 (85.9%) initially examined type
      1 diabetic patients formed the basis for this 5-year follow-up study. MAIN
      OUTCOME MEASURES: The degree of retinopathy was based on fundus photography or
      biomicroscopy. Degree of metabolic control was assessed by HbA1c levels, signs of
      nephropathy by albumin creatinine clearance ratio and urinary albumin levels.
      Blood pressure was measured in the supine position. Duration of diabetes, age,
      and insulin dosage were registered. RESULTS: The incidence of retinopathy was
      47.2% and progression from background to severe retinopathy occurred in 41%. Risk
      indicators for the development of retinopathy were duration of diabetes (P <
      0.001), degree of metabolic control (P < 0.001), insulin dosage (P < 0.05) and
      signs of nephropathy based on measurements of albumin creatinine clearance ratio
      (P < 0.01) and urinary albumin concentration (P < 0.05). Two risk indicators
      could be identified for progression of retinopathy, i.e. the degree of metabolic
      control (P < 0.01) and diastolic blood pressure (P < 0.05). CONCLUSIONS: The
      results suggest that apart from poor metabolic control, development of
      retinopathy in type 1 diabetes is associated with long diabetes duration and
      clinical signs of diabetic nephropathy. Progression of retinopathy is associated
      with poor metabolic control and elevated diastolic blood pressure levels.

PMID- 8151271
TI  - Pheochromocytoma without hypertension.
AB  - Pheochromocytoma is a rare tumour which is usually suggested by sustained or
      paroxysmal hypertension. Our patient with a pheochromocytoma was unusual for two
      reasons: she was normotensive during 3 weeks of close observation in the hospital
      and the urinary adrenaline level was higher than the noradrenaline level. In the
      patient's history there were no data on hypertension attacks. The patient had a
      palpable abdominal mass and the cytological finding was in contrast with a
      clinical diagnosis of pheochromocytoma. The surgery revealed a tumour and the
      pathohistologic evaluation established the diagnosis of pheochromocytoma. After
      surgery, the patient's urinary catecholamine levels reverted to normal. Our
      patient may have been normotensive because her tumour predominantly secreted
      adrenaline and perhaps other vasodilating substances.

PMID- 8151270
TI  - Fulminant hepatitis with severe lactate acidosis in HIV-infected patients on
      didanosine therapy.
AB  - We report two cases of fulminant hepatic failure in HIV-1-infected patients
      treated with didanosine (ddI). Clinical manifestations including vomiting,
      diarrhoea and dyspnoea were identical in both cases. Biological data mainly
      revealed hepatic failure and lactic acidosis. Histological examination of liver
      biopsies showed diffuse microvesicular steatosis. The outcome was fatal in both
      patients. The only comparable case previously reported (Lai et al., 1991) showed
      close similarities in the clinical, biological and histological manifestations
      with microvesicular steatosis. This prompted us to suspect that ddI might be
      responsible for fulminant hepatitis in all three AIDS patients. This toxic effect
      may be added to the list of potential adverse events occurring during ddI
      therapy.

PMID- 8151269
TI  - Effects of captopril on renal function in healthy uninephrectomized subjects and
      in healthy control subjects.
AB  - OBJECTIVES: To study the importance of the renin-angiotensin-II system for renal
      haemodynamics and sodium and water handling in the adapted remnant kidney in
      healthy uninephrectomized subjects. DESIGN: Case-control study. SETTING: All
      subjects were investigated at laboratory C, Department of Medicine and
      Nephrology, Skejby Hospital. SUBJECTS: Fourteen healthy uninephrectomized (Unx)
      and 14 matched healthy control subjects (Cs). INTERVENTION: Captopril, 25 mg
      orally. MAIN OUTCOME MEASURES: The glomerular filtration rate (GFR) and renal
      plasma flow (RPF) were measured by the constant infusion clearance technique
      using 125I-iothalamate and 131I-hippuran as reference substances, tubular
      function was evaluated by the lithium clearance technique (CLi), urinary flow
      rate (V), sodium excretion (UNaV), fractional sodium excretion (FENa), mean blood
      pressure (MBP) and heart rate (HR) were measured by conventional methods and
      plasma levels of angiotensin II (Ang-II), aldosterone (Aldo), arginine
      vasopressin (AVP) and atrial natriuretic peptide (ANP) were measured by
      radioimmunoassay. RESULTS: In both groups captopril ingestion resulted in a
      significant decrease in the MBP (Unx: 87.1 to 83.5 and Cs: 86.8 to 83.8 mmHg,
      median values), filtration fraction (Unx: 24.6 to 22.1 and Cs: 24.1 to 22.5%,
      median values) and Ang-II (Unx: 10.5 to 7.7 and Cs: 12 to 7.6 pmol-1, median
      values). Single kidney GFR, V, and CLi were unchanged in both groups. FENa and
      single kidney RPF were significantly increased in only the Cs group; FENa (Unx:
      1.81 to 1.91 and Cs: 1.56 and 1.90%, median values). The plasma level of ANP was
      significantly decreased in only the Unx group. CONCLUSION: The data suggest that
      sodium handling in the remnant kidney in uninephrectomized subjects could be less
      sensitive to Ang-II than in healthy control subjects, and that this might be as a
      result of adaptive changes in the distal parts of the nephron.

PMID- 8151272
TI  - Chronic lymphocytic leukaemia complicated by chylothorax.
AB  - Chylothorax is a very rare complication of chronic lymphocytic leukaemia: we
      describe an 81-year-old woman with chronic lymphocytic leukaemia complicated by
      chylothorax. Treatment with mediastinal irradiation and chemotherapy was
      unsuccessful. The pleural effusion resolved after talc pleurodesis.

PMID- 8151273
TI  - Monoplegia following carotid sinus massage.
AB  - Serious complications after carotid sinus massage are rare. A case is described
      of monoplegia complicating carotid sinus massage in an elderly patient without
      symptoms or signs of cerebrovascular disease. We remind physicians of this
      potential complication and suggest that alternative therapies be considered prior
      to the use of carotid sinus massage in this age group.

PMID- 8151274
TI  - Toward a redefinition of implicit memory: process dissociations following
      elaborative processing and self-generation.
AB  - Does conceptual processing affect unconscious uses of memory? We used a process
      dissociation procedure to separate automatic (unconscious) and consciously
      controlled uses of memory in a stem-completion task. Contrary to results from
      indirect test conditions, estimates derived from our procedure showed no effect
      of self-generation and no differential effect of semantic and nonsemantic study
      conditions on automatic uses of memory. These results provide evidence that (a)
      indirect tests are often contaminated by conscious uses of memory and (b) stem
      completion is highly dependent on prior perceptual (and perhaps lexical)
      processing. The experiments demonstrate the advantages of using process
      dissociation procedures over comparisons between direct and indirect tests.

PMID- 8151275
TI  - Unconscious perception: attention, awareness, and control.
AB  - Conscious perception is substantially overestimated when standard measurement
      techniques are used. That overestimation has contributed to the controversial
      nature of studies of unconscious perception. A process-dissociation procedure (L.
      L. Jacoby, 1991) was used for separately estimating the contribution of conscious
      and unconscious perception to performance of a stem-completion task. Unambiguous
      evidence for unconscious perception was obtained in 4 experiments. In Experiment
      1, decreasing the duration of a briefly presented word diminished the
      contribution of both conscious and unconscious perception. In Experiments 2-4,
      dividing attention reduced the contribution of conscious perception while leaving
      that of unconscious perception unchanged. Discussion focuses on the measurement
      of awareness and the relation between perception and memory.

PMID- 8151276
TI  - Effects of solving related proofs on memory and transfer in geometry problem
      solving.
AB  - Three experiments investigate the relationship between memory and problem solving
      in the domain of geometry theorem proving. In Experiment 1, Ss memories for an
      original problem-solving episode were interfered with retroactively by solving a
      2nd problem that had the same diagram, but no memory effects were observed that
      depended on the second problem's logical similarity to the original. Results
      suggest that the diagram is the basis for geometry problem-solving memories.
      Experiments 2 and 3 investigated problem-solving memories in use by examining Ss
      transfer to a 3rd (test) problem. As with the memory results, transfer was
      reduced when the 1st two problems had the same diagram relative to when they had
      2 different diagrams. Transfer was reduced most in the condition with the
      greatest proportion of memory-interfering steps. Results suggest that the
      structure and quality of problem-solving memories affect problem-solving
      transfer.

PMID- 8151277
TI  - Similarity and property effects in inductive reasoning.
AB  - Three experiments investigated the proposal that inductive inferences about
      different properties depend on different measures of similarity. In Experiments 1
      and 2, Ss were given the premise that a category of animals has some property and
      judged the probability that another category of animals also has that property.
      Ss made the strongest inferences when the kind of property (anatomical or
      behavioral) corresponded to the kind of similarity between the animal categories
      (anatomical or behavioral). These results cannot be explained in terms of a
      single measure of similarity underlying induction. In Experiment 3, Ss rated the
      similarity of animal pairs with respect to anatomy or behavior. Regression
      analyses showed that both behavioral and anatomical similarity influenced
      behavioral inferences, but only anatomical similarity influenced anatomical
      inferences.

PMID- 8151278
TI  - Composition during serial learning: a serial position effect.
AB  - Composition is a computational learning mechanism that merges serially performed
      elementary processes into hierarchically organized knowledge structures. The main
      goals of this research were to explore (a) the role of serial position in
      composition and (b) the relation between degree of composition and explicit
      serial recall in serial learning. In 3 experiments, Ss performed a rule-based
      serial reaction time task in which they had to categorize a sequence of 12
      stimuli shown simultaneously on a video monitor. A procedure based on the
      comparison of reaction times to random sequences and a repeating sequence
      identified a serial position effect of composition that was, however, moderated
      by Ss' explicit, postexperimental recall of the repeating sequence. A production
      system-based computational model of composition is described that qualitatively
      reproduces the empirical findings. Implications for the mechanisms governing
      serial learning are discussed.

PMID- 8151279
TI  - Category invention in unsupervised learning.
AB  - This research aimed to discriminate between 2 general approaches to unsupervised
      category learning, one based on learning explicit correlational rules or
      associations within a stimulus domain (autocorrelation) and the other based on
      inventing separate categories to capture the correlational structure of the
      domain (category invention). An "attribute-listing" paradigm was used to index
      unsupervised learning in 3 experiments. Each experiment manipulated the order in
      which instances from 2 different categories were presented and evaluated the
      effects of this manipulation in terms of the 2 competing theoretical approaches
      to unsupervised learning. Strong evidence was found for the use by Ss of a
      discrete category invention process to learn the categories in these experiments.
      These results also suggest that attribute listing may be a valuable method for
      future investigations of unsupervised category learning.

PMID- 8151280
TI  - Mechanisms underlying reduction in Stroop interference with practice for young
      and old adults.
AB  - Age-related factors in the reduction of Stroop interference with practice were
      examined in 3 studies. Young and old adults received extensive practice on a
      modified version of the Stroop task. Both groups showed reduced interference on
      the Stroop task with practice. Results suggest that young adults' reduction in
      Stroop interference was due to general task factors plus the development of a
      reading suppression response. The old adults' reduction in Stroop interference
      was attributed primarily to general task factors. Results indicate that old
      adults have greater difficulty than young adults in developing new automatic
      processes and modifying existing automatic processes. The implication of these
      findings for current models of Stroop interference is that, in addition to
      automatic processing, attentional mechanisms must be incorporated to account for
      the age-related differences.

PMID- 8151282
TI  - DNA typing: approaches and applications.

PMID- 8151281
TI  - Quantitative immunoblot detection of rare proteins in whole cell extracts using
      biotin-strepavidin reagents.
AB  - A novel immunoblotting method designed for quantitative detection of low copy
      number proteins in crude cell extracts is presented. This technique can be used
      with either mono- or poly-clonal antibodies and utilizes the sensitivity and
      amplification of the high affinity interaction between biotin and strepavidin.
      Radioactive iodination of the strepavidin moiety allows for rapid and accurate
      quantification of proteins bound to nitrocellulose. This biotin/125I-strepavidin
      technique is highly reproducible and can detect as little as 1 ng of protein. In
      addition, use of biotinylated secondary antibodies directed against a specific
      type of primary antibody avoids the problem of low affinity recognition of
      immunoglobulins from certain species by protein A. Finally, the methodology is
      simple and convenient, and secondary and tertiary reagents are commercially
      available. The application of this technique is illustrated in the determination
      of relative quantities of the tight junction-associated protein ZO-1, present in
      very small amounts in epithelial cells. This same technique can also be used for
      the quantitative analysis of relatively more abundant cellular constituents or
      purified protein.

PMID- 8151283
TI  - Statistical interpretation of DNA evidence.

PMID- 8151284
TI  - Population genetics of DNA profiles.

PMID- 8151285
TI  - DNA profiling and crime investigation--the European context.

PMID- 8151286
TI  - The evidential value of DNA profiles.

PMID- 8151287
TI  - Genomic variation of human immunodeficiency virus type 1 (HIV-1): molecular
      analyses of HIV-1 in sequential blood samples and various organs obtained at
      autopsy.
AB  - Length polymorphisms and partial nucleotide sequences were determined for the
      hypervariable regions, V1 to V5, of the human immunodeficiency virus type 1 (HIV
      1) env gene obtained from proviral DNA of sequential peripheral blood samples,
      from viral RNA in plasma, and from proviral DNA obtained from different organs of
      individuals at autopsy. The lengths of several env regions of HIV-1 proviral DNA
      differed markedly when obtained from different organs of an individual.
      Nucleotide sequences of the hypervariable V3 region of HIV-1 obtained from
      different organs of one patient demonstrated distinct viral variants. Most
      proviral DNA sequences found in organs were also present in viral RNA obtained
      from plasma. The majority of HIV-1 V3 variants present in the lymph tissue could
      be found in the plasma viral population obtained at autopsy and in the sequential
      blood samples obtained before death, but were absent from the cardiac blood
      provirus population obtained at autopsy. However, sequence variants found in the
      brain proviral DNA were not detected in either plasma or the sequential blood
      samples. Sequence differences were observed at the apex of the V3 loop between
      HIV-1 variants present in sequential blood samples and in blood lymphocytes and
      nervous tissue, lymph tissue and plasma obtained post-mortem. The potential
      effect of lymph tissue on the long-term persistence of different viral variants
      is discussed. Virus obtained from the two sequential blood samples produced
      syncytia in primary cultures and was easily transmitted to the continuous JM cell
      line. Consensus (majority) V3 loop sequences determined for the adapted viruses
      demonstrated that some, but not all, sequences were represented within the in
      vivo viral population.

PMID- 8151288
TI  - Structural proteins and DNA characteristics of 14 Listeria typing bacteriophages.
AB  - The major structural proteins of 13 temperate and one virulent Listeria typing
      bacteriophages were analysed and compared using isoelectric focusing in
      immobilized pH gradients (IPG), ultrathin-layer two-dimensional electrophoresis,
      amino acid analysis and N-terminal amino acid sequences of selected proteins.
      Isoelectric points for major capsid and tail proteins of the 12 members of the
      siphoviridae family included in this study ranged from 4.70 to 5.92, whereas one
      of the two myoviridae investigated (B054) showed structural proteins in the 6.1
      to 6.3 range. In comparison to protein profiles from one-dimensional SDS gels,
      the IPG technique gave better resolution and improved discrimination of phage
      proteins. Combination of this technique and SDS gel electrophoresis made it
      possible to correlate M(r) and isoelectric points of major structural proteins.
      Tail polypeptides of all siphoviridae are smaller and, with one exception, more
      acidic than their corresponding capsid counterparts. We also determined the amino
      acid composition of capsid and tail proteins. When compared with an average
      protein, they were found to be fairly rich in acidic and short-chain hydrophobic
      amino acids, as well as in lysine. In addition, the N-terminal amino acid
      sequences of major capsid and tail proteins of four representative listeriaphages
      were compared. The base composition of listeriaphage DNAs was between 37% and 39%
      G + C, reflecting that of their bacterial hosts. Each phage had a distinct
      restriction endonuclease pattern, and genome sizes ranged from 35 to 116 kb. DNA
      DNA hybridization permitted the identification of five DNA homology groups. The
      two myoviruses studied (A511 and B054) showed no DNA homology to other phages,
      confirming their unique nature. The 12 siphoviruses were classified into three
      DNA homology groups with little cross-homology. Furthermore, phage A006 was found
      to share little DNA homology with the other investigated members of species 2671.
      Therefore, a new species (A006) is proposed. With respect to phage classification
      and taxonomy, a good correlation between the various approaches was observed,
      mostly corresponding to particle morphology.

PMID- 8151289
TI  - Nucleotide sequence of the carlavirus associated with blueberry scorch and
      similar diseases.
AB  - We have synthesized and mapped a library of cDNA clones representing the RNA
      genome of a strain of blueberry scorch carlavirus (BBScV) associated with a
      disease known locally, in New Jersey, U.S.A., as Sheep Pen Hill disease. The
      nucleotide sequence of that strain was determined to be 8514 residues, excluding
      the poly(A) tail. In addition, cDNA clones representing the 3' terminus of
      another strain of the virus from the same field were synthesized, mapped and
      sequenced. The overall identity between sequences of these two strains was
      approximately 90% spanning the 1634 residue overlap, confirming their identity as
      distinct strains and not simply different isolates of a single strain. Finally,
      the coat protein gene of a distinct strain of the virus, isolated from plants
      with blueberry scorch disease in the Puyallup Valley in Washington State, U.S.A.,
      was cloned from total cDNA by PCR. Sequence analysis revealed that the strain
      from Washington was more divergent from the two New Jersey strains than they were
      from each other. Comparisons of these sequences with other carlavirus sequences
      indicated that BBScV is more closely related to lily symptomless virus and potato
      virus S than to potato virus M, Helenium virus S, carnation latent virus or
      poplar mosaic virus. BBScV and potato virus M shared approximately 54% nucleotide
      sequence identity overall.

PMID- 8151290
TI  - Simultaneous regulation of tomato golden mosaic virus coat protein and AL1 gene
      expression: expression of the AL4 gene may contribute to suppression of the AL1
      gene.
AB  - The tomato golden mosaic virus (TGMV) coat protein and AL1 genes are located in
      opposite directions on either side of an intergenic region. To enable the effects
      of the AL1, AL2 and AL3 gene products on expression of the coat protein and AL1
      genes to be studied simultaneously, a plasmid was constructed, containing the
      intergenic region linked on one side to a 5'-terminal portion of the AL1 gene
      fused to a beta-glucuronidase (GUS) reporter gene (to replace most of the AL1
      gene) and on the other side to a neomycin phosphotransferase (NEO) reporter gene
      (to replace the coat protein gene). This GUS-NEO plasmid was mixed with plant
      expression plasmids containing the AL1, AL2 or AL3 coding regions, the DNA was
      transformed into Nicotiana benthamiana protoplasts and GUS activities and NEO
      protein levels were measured. Control transformations were carried out with the
      GUS-NEO plasmid mixed with the AL1, AL2 or AL3 plasmids in which mutations were
      introduced to prevent translation of the open reading frames (ORFs). The results
      showed that transactivation of the coat protein gene by the AL2 gene product and
      suppression of the AL1 gene by the expression of AL1 DNA (both reported
      previously) can occur simultaneously. It was also shown that expression of AL4, a
      small ORF contained within AL1 DNA but in a different reading frame, as well as
      expression of ORF AL1, can cause significant suppression of AL1 gene expression.
      Neither the AL1 nor the AL3 gene products affected the expression of the coat
      protein gene.

PMID- 8151291
TI  - A stable 463 nucleotide variant of citrus exocortis viroid produced by terminal
      repeats.
AB  - An unusual variant of citrus exocortis viroid (CEV) was detected when an inoculum
      source from Gynura aurantiaca D.C. was used to infect a hybrid tomato
      (Lycopersicon esculentum Mill. x L. peruvianum). The 92 nucleotide larger
      variant, CEV D-92, which displayed the characteristic circular and linear viroid
      structural forms, contained two repeated sequences spanning the V and T2 domains.
      A dramatic moderation of symptom expression in Gynura accompanied the
      incorporation of these repeated sequences. A comparison of the sequence and
      structure of CEV D-92 with coconut cadang-cadang viroid revealed similarities in
      the regions generating the naturally occurring terminal repeats suggesting a
      possible preferred site for RNA recombination between viroids.

PMID- 8151292
TI  - Characterization of the herpes simplex virus type 1 strain 17+ neurovirulence
      gene RL1 and its expression in a bacterial system.
AB  - The DNA sequence of herpes simplex virus type 1 (HSV-1) strain 17+ in the region
      coding for the polypeptide ICP34.5 predicts a protein of 248 amino acids with a
      proposed M(r) of 26,158. The entire RL1 open reading frame was cloned into the
      expression vector pET8c to enable over-expression of ICP34.5 in Escherichia coli.
      The expressed protein was partially purified and used as an immunogen to produce
      a polyclonal antiserum in rabbits. Construction of an ICP34.5 null mutant (1771),
      demonstrated that the predicted open reading frame for ICP34.5 in strain 17+ is
      correct and confirmed that HSV-1 strain 17+ ICP34.5 specifically determines
      neurovirulence. The specificity of the anti-serum directed against the E. coli
      expressed ICP34.5 was defined by Western blotting of wild-type and RL1-negative
      infected cell extracts.

PMID- 8151293
TI  - Binding and repression of the latency-associated promoter of herpes simplex virus
      by the immediate early 175K protein.
AB  - We demonstrate that the immediate early 175K protein (IE175K) of herpes simplex
      virus type 1 binds to the cap site of the latency-associated promoter (LAP) in an
      unusual manner. The complex formed on the LAP cap site was significantly larger
      than that formed on the IE175K cap site and the requirements for binding were
      qualitatively distinct with respect to both the primary sequence determinants at
      the site, and the regions of IE175K protein required for binding compared to
      those for the IE175K cap site. Although purified IE175K was sufficient for this
      large complex formed on the LAP cap site, the DNA-binding domain was unable to
      bind efficiently. This contrasted strikingly with the IE175K cap site where,
      using precisely analogous probes, the DNA-binding domain exhibited a strong
      interaction. Surprisingly, from dissociation kinetics we show that binding of the
      intact protein to the LAP cap site is considerably more stable than the binding
      of IE175K to its own cap site (half-lives of the complexes 15 min and < 1 min
      respectively), and this was reflected in more efficient repression of LAP-driven
      expression than IE175K promoter-driven expression by IE175K. Moreover, primary
      sequence requirements for IE175K binding to the LAP cap site region differed from
      previously identified IE175K recognition sequences in that in addition to a
      partially conserved consensus sequence, neighbouring bases were necessary for
      binding. Although the LAP cap site exhibits a pseudopalindromic arrangement of
      core consensus sites, we show that this is not the basis for the higher order,
      more stable binding to this region. Together these results indicate that IE175K
      forms an unusual complex at the LAP cap site, broadening the range of previously
      defined sequences recognized by IE175K.

PMID- 8151294
TI  - Tumour necrosis factor-alpha production during cytomegalovirus infection in
      immunosuppressed rats.
AB  - The production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL
      6, all proinflammatory cytokines, was investigated in radiation-immunosuppressed
      rats infected with rat cytomegalovirus (RCMV). At day 7 post-infection, when the
      animals showed disease signs, high TNF-alpha levels were detected in the serum
      and in homogenates of various organ tissues. In contrast, IL-1 and IL-6 levels
      were not significantly elevated. Moreover, replication of RCMV induced TNF-alpha
      expression in different types of cells grown in vitro. When frozen tissue
      sections were examined by immunohistology, TNF-alpha-producing cells were found
      in areas with extensive pathology in the lungs, spleen and liver. Both
      lymphocytes and RCMV-infected cells were identified as the sources of TNF-alpha.
      Its abundance in RCMV-infected rats suggests an important role for TNF-alpha in
      CMV pathogenesis.

PMID- 8151295
TI  - Characterization of the 55K adenovirus type 5 E1B product and related proteins.
AB  - In addition to major proteins of 19K and 55K (176 and 496 residues, 176R and
      496R, respectively), early region 1B (E1B) of human adenovirus type 5 (Ad5) is
      predicted to encode at least three other polypeptides of 156R, 93R and 84R that
      share 79 amino-terminal residues with 496R. We have used a series of specific
      antipeptide sera to identify and partially characterize these proteins. 84R was
      produced in large amounts, 156R somewhat less, and 93R at very low levels.
      Synthesis of 176R, 496R, as well as the E2A 72K DNA-binding protein commenced
      shortly after that of E1A proteins in Ad5-infected KB cells. Production of 156R,
      93R and 84R began somewhat later, but prior to the synthesis of the late
      structural protein IX and hexon. 156R, which is composed of the 79 amino-terminal
      and 77 carboxy-terminal amino acids of 496R, migrated on SDS-PAGE as two species
      which appeared to differ by their degree of phosphorylation. 156R and 496R
      yielded identical tryptic phosphopeptides that contained both phosphoserine and
      phosphothreonine, and one of these was immunoprecipitated by a serum specific for
      the carboxy terminus. These results suggested that Ser-490 and/or Ser-491 as well
      as Thr-495 are major sites of phosphorylation in these proteins.

PMID- 8151296
TI  - Cytotoxic T lymphocytes raised against Japanese encephalitis virus: effector cell
      phenotype, target specificity and in vitro virus clearance.
AB  - Several H-2 defined cell lines were examined for their ability to support
      infection and replication of Japanese encephalitis virus (JEV) before their use
      in in vitro and in vivo stimulation protocols for generating cytotoxic T
      lymphocytes (CTLs) against JEV. Among 11 different cell lines tested, two H-2d
      macrophage tumour lines (P388D1, RAW 264.7), an H-2d hybridoma (Sp2/0), an H
      2KkDd neuroblastoma (Neuro 2a), and H-2k fibroblast cell line (L929) were found
      to support JEV infection and replication. These cell lines were used to generate
      anti-JEV CTLs by using in vivo immunization followed by in vitro stimulation of
      BALB/c mice. We observed that not only syngeneic and allogeneic infected cells
      but also JEV-infected xenogeneic cells could prime BALB/c mice for the generation
      of JEV-specific CTLs upon subsequent in vitro stimulation of splenocytes with JEV
      infected syngeneic cells. Although infected xenogeneic cells were used for
      immunization, the anti-JEV effectors that were generated lysed infected syngeneic
      targets but not JEV-infected xenogeneic or allogeneic target cells in a 5 h 51Cr
      release assay. These anti-JEV effectors recognized syngeneic target cells
      infected with West Nile virus to a lesser extent and were shown to be Lyt-2.2+ T
      cells. The results of unlabelled cold target competition studies suggested
      alterations in the cell surface expression of viral antigenic determinants
      recognized by these CTLs. We further demonstrate that the JEV-specific CTLs
      generated could virtually block the release of infectious virus particles from
      infected P388D1 and Neuro 2a cells in vitro.

PMID- 8151297
TI  - The nucleoprotein of Marburg virus is phosphorylated.
AB  - The nucleoprotein (NP) of Marburg virus (MBG), a filovirus, is encoded by the
      gene closest to the 3' end of the non-segmented negative-strand RNA genome.
      Sequence comparison has indicated that NP is the functional equivalent to the
      nucleoproteins of paramyxoviruses and rhabdoviruses. Expression of recombinant NP
      in two eukaryotic systems using vaccinia virus and baculovirus (vectors pSC11 and
      pAcYMB1, respectively) and analysis of MBG-specific proteins have demonstrated
      that the NP of MBG is phosphorylated. The NP appeared in two forms differing in
      M(r) by about 2K (94K and 92K respectively). Dephosphorylation clearly
      demonstrated that the 94K form is phosphorylated whereas the 92K form is
      unphosphorylated. In virion particles NP was exclusively present in the
      phosphorylated form. These findings suggest that only the phosphorylated NP can
      form nucleocapsid complexes and interact with the genomic RNA.

PMID- 8151298
TI  - Reversal of the measles virus-mediated increase of phosphorylating activity in
      persistently infected mouse neuroblastoma cells by anti-measles virus antibodies.
AB  - To investigate the effect of persistent measles virus infection on signal
      transduction in cells of neuronal origin, the mouse neuroblastoma cell line
      NS20Y/MS, which is persistently infected with measles virus, was used. The
      results demonstrate an approximate 50% increase in total phosphorylation and a
      similar increase in protein kinase C (PKC) activity. Western blot analysis with
      anti-total PKC or anti-PKC-alpha antibodies revealed a significant increase in
      the level of an 80K immunoreactive PKC in NS20Y/MS cells. Following incubation of
      NS20Y/MS cells with polyclonal anti-measles virus antibodies, which down-regulate
      the level of measles virus proteins, total and PKC-mediated phosphorylation
      returned to the basal level of uninfected cells. This effect was reversible and
      removal of the antibodies resulted in restoration of the high level of total and
      PKC-mediated phosphorylation. The release of infectious measles virus was
      strongly inhibited by incubation of NS20Y/MS cells with the PKC inhibitor, 1-(5
      isoquinolinylsulphonyl)-2-methylpiperazine (H-7). These results demonstrate that
      measles virus induces elevation in cellular phosphorylation which is essential
      for measles virus production.

PMID- 8151299
TI  - Identification and characterization of the ecdysteroid UDP-glucosyltransferase
      gene of the Lymantria dispar multinucleocapsid nuclear polyhedrosis virus.
AB  - We have located, cloned, sequenced and characterized the ecdysteroid UDP
      glycosyltransferase gene (egt) gene from the baculovirus Lymantria dispar
      multinucleocapsid nuclear polyhedrosis virus. (LdMNPV), which is specific for the
      gypsy moth (L. dispar). The egt gene from the related baculovirus Autographa
      californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) disrupts the
      hormonal balance of the host larva by galactosylating ecdysone, which prevents
      moulting. The location of the LdMNPV egt gene, determined by hybridization
      analysis using a cloned coding segment of the AcMNPV egt gene, was mapped to
      between 79.1 and 80.2 map units on the viral genome. This region contains an open
      reading frame of 1464 nucleotides capable of encoding a 55K polypeptide. This
      predicted protein exhibits a 42% amino acid identity with the AcMNPV egt
      polypeptide. Transcripts of the egt gene were analyzed by Northern blot and
      primer extension. The egt gene is transcribed from approximately 12 to 48 h, and
      maximally at about 16 h post-infection. Transcription occurred in the presence of
      aphidicolin, a viral DNA synthesis inhibitor, but not in the presence of
      cycloheximide, a protein synthesis inhibitor. Therefore the LdMNPV egt gene is
      classified as a delayed early gene. The egt gene is transcribed in a clockwise
      direction with respect to the circular map, and transcription initiates at a
      single site. Comparisons between the two baculoviral egt proteins and mammalian
      UDP-glucuronosyltransferases reveal areas which are conserved between the
      mammalian and baculoviral genes, as well as areas that are only conserved in the
      viral egt proteins. The LdMNPV protein sequence appears to include a signal
      peptide, which would allow the protein to be secreted into the haemolymph.

PMID- 8151300
TI  - Analysis of the human immunodeficiency virus type 1 envelope protein interaction
      with the CD4 host cell receptor.
AB  - A secreted form of human immunodeficiency virus type 1 (HIV-1) envelope
      glycoprotein (gp160s), expressed in HeLa cells from a vaccinia virus recombinant
      was analysed by velocity-gradient centrifugation and chemical cross-linking. We
      showed that gp160s existed predominantly as a dimer, but higher forms
      corresponding to trimers and tetramers were also found. Soluble CD4 (sCD4) and
      native CD4 expressed by recombinant vaccinia viruses were analysed by sucrose
      gradient sedimentation alone or after complexing with gp160s. The sCD4 sedimented
      in sucrose gradients as a monomer, whereas after solubilization the native CD4
      was in a dimeric state. Both forms of CD4 were able to form complexes when
      incubated with gp160s. In the case of the sCD4, the M(r) corresponded to a
      (sCD4)2-(gp160s)2 complex, whereas with CD4 the complexes were of a greater order
      of magnitude. HIV gp120 was secreted into the medium in a monomeric state. With
      sCD4 it gave a one-to-one complex, whereas with the native CD4 high M(r)
      complexes were formed. The importance of the oligomeric state of the virus- and
      cell-receptor proteins are discussed regarding their avidities.

PMID- 8151301
TI  - Correlation between high level gp160 expression and reduced CD4 biosynthesis in
      clonal derivatives of human immunodeficiency virus type 1-infected U-937 cells.
AB  - We have compared cytoplasmic CD4 mRNA accumulation, CD4 biosynthesis and steady
      state levels of both CD4 protein and mRNA in a variety of clonal derivatives of U
      937 cells, chronically infected with human immunodeficiency virus type 1 IIIB
      (HIV-1), that express various cellular and viral phenotypes. These phenotypes
      included defective processing of either gp160 or Gag-Pol, viruses with severely
      limited host-range, and inability to generate viral products. All clones, with
      the exception of the one that failed to generate viral mRNA and proteins, did not
      express cell surface CD4. Furthermore, each of these clones had steady-state
      levels of CD4 mRNA which were either equivalent to or higher than those of the
      parental U-937 cell line. Patterns of cytoplasmic CD4 mRNA levels resembled those
      of total RNA, suggesting that CD4 mRNA transport from the nucleus to the
      cytoplasm was unaffected by HIV-1 infection. Profiles of steady-state levels of
      the CD4 protein resembled those of CD4 mRNA in the UHC clones, but CD4
      biosynthesis was reduced in all clones with the exception of that which failed to
      express viral products. This report is the first demonstration that steady-state
      CD4 biosynthesis is reduced in HIV-1-infected cells. In general, there was a good
      correlation between high levels of expression of gp160 and reduced CD4
      biosynthesis. These results suggest that HIV-1 env gene products may contribute
      to the observed reduction in levels of CD4 biosynthesis.

PMID- 8151302
TI  - Expression of functional protease and subviral particles by vaccinia virus
      containing equine infectious anaemia virus gag and 5' pol genes.
AB  - Cells infected with vaccinia viruses expressing the equine infectious anaemia
      virus (EIAV) gag gene (VGag) or gag plus the 5' pol encoding protease (VGag/PR)
      were evaluated with monoclonal antibody to a p26 capsid protein linear epitope
      (QEISKFLTD). Both recombinant viruses expressed Gag precursor protein (55K)
      whereas only VGag/PR expressed a detectable Gag-Pol fusion protein (82K) with a
      functional protease, shown by subviral particles containing processed p26. Horses
      inoculated with VGag/PR produced antibodies reactive with EIAV Gag proteins.

PMID- 8151303
TI  - Expression of bovine herpesvirus 1 glycoprotein gIII by a recombinant baculovirus
      in insect cells.
AB  - Bovine herpesvirus 1 (BHV-1) glycoprotein gIII functions both as a major virus
      attachment protein and haemagglutinating protein. Here we constructed recombinant
      baculovirus incorporating the BHV-1 gIII coding sequence to characterize the
      expression, function and immunogenicity of the glycoprotein in insect cells. The
      recombinant gIII had an M(r) of 72K and seemed to form homodimers. The gIII was
      expressed on the surface of insect cells and a rosette formation assay
      demonstrated haemadsorbing activity of the glycoprotein. Antigenic authenticity
      of the recombinant gIII was confirmed by a panel of monoclonal antibodies
      specific for the glycoprotein produced in mammalian cells. Antisera raised to
      recombinant gIII neutralized the infectivity of BHV-1. These data suggest that
      recombinant gIII produced in insect cells may be a useful immunogen in a BHV-1
      vaccine.

PMID- 8151304
TI  - Transcriptional analysis and genome expression of chicken anaemia virus.
AB  - Strand-specific riboprobes representative of either strand of the chicken anaemia
      virus (CAV) replicative form (RF) DNA indicated that only one strand of the RF
      was transcribed to produce a major 2.0 kb transcript and that the encapsidated
      DNA strand was of negative sense. Primer extension analysis located a single
      transcriptional start site at nucleotide position 360 of the CAV sequence.
      Amplification, cloning and sequencing of the 3' end of the major transcript
      revealed the polyadenylation site at nucleotide position 21. Northern blot
      analysis using a series of genomic probes indicated that the 2.0 kb transcript
      was devoid of splicing and identified a non-transcribed region of the genome.
      This non-transcribed region was shown to possess promoter activity, enhancing the
      expression of the human growth hormone reporter gene in a transient gene
      expression assay. These observations suggest a simple strategy of genome
      expression involving a functional polycistronic message.

PMID- 8151305
TI  - Sequence variation in the capsid protein genes of human papillomavirus type 16.
AB  - We have cloned and sequenced the L1 and L2 genes from human papillomavirus type
      16 (HPV16) DNA-containing cervical cytology samples collected from the U.K. and
      Trinidad. Samples containing high copy numbers of HPV16 DNA were selected as
      being likely to contain fully functional virus DNA molecules in an episomal
      state, rather than in an integrated and possibly altered state. In comparison
      with the previously published sequence of HPV16 isolated from an invasive cancer
      a variety of differences were detected in both L1 and L2. The pattern of changes
      appears to be different in samples from the two geographic regions. One of the
      differences (resulting in D at position 202 of the L1 protein) reported recently
      to be functionally important for virus particle assembly was found to occur in
      all the samples examined. Variations in L1 found within known immunoreactive
      regions or hydrophobic domains should be taken into account in design of
      prophylactic vaccines for HPV16 based on virus-like particles. All variations
      within L2 protein were found in hydrophilic domains in the carboxy-terminal half
      of L2. These positions were highly variable among other types of papillomavirus
      and are located outside the known L2 immunoreactive region.

PMID- 8151306
TI  - Effect of frameshift mutation in the pre-C region of hepatitis B virus on the X
      and C genes.
AB  - We have previously cloned a mutant hepatitis B virus (HBV) genome which had one
      thymidine addition in the pre-C region resulting in a frameshift mutation in the
      pre-C region and fusion of the X and C genes. We constructed plasmids containing
      serially deleted and/or back-mutated (authentic) pre-C regions to study the
      effect of the frameshift mutation. COS cells transfected with plasmids containing
      the frameshifted pre-C region produced a 21K C protein (P21c) but not a 22K
      partially processed pre-C protein (P22). On the other hand, COS cells transfected
      with plasmids containing the back-mutated pre-C region produced P22. This result
      was also observed in HepG2-K8 cells producing the mutant HBV particles.
      Therefore, the pre-C region of HBV is likely to be non-essential for virus
      replication. COS cells transfected with the plasmid containing a fused X-C open
      reading frame (ORF) produced a 40K X-C fusion protein. This X-C fusion protein
      exerted transcriptional trans-activation. These results suggest that the mutant
      HBV has a C gene with a defective pre-C region and a fused X-C ORF, and hence
      cannot synthesize 16K HBeAg (P16e).

PMID- 8151307
TI  - Hepatitis C virus variants from Nepal with novel genotypes and their
      classification into the third major group.
AB  - Five isolates of hepatitis C virus (HCV) RNA from patients with chronic liver
      disease in Nepal were not classifiable into the known genotypes I/1a, II/1b,
      III/2a, IV/2b or V/3a using PCR with type-specific primers deduced from the HCV
      core gene. Their nucleotide sequences were determined for the 5'-terminal 1.5
      kilobases and 3'-terminal 1.2 kilobases, covering 30% of the entire genome, and
      compared with each other and with reported sequences of HCV isolates of various
      genotypes. They were more similar to a reported HCV isolate (NZL1) of genotype
      V/3a (in 81.6 to 84.1% of their nucleotides and 85.7 to 88.7% of the deduced
      amino acid sequence) compared with the genotypes I/1a to IV/2b (in 69.3 to 74.7%
      and 72.3 to 77.4%, respectively). Hence they were considered to be variants of
      the third major group (group 3). The five HCV isolates shared 81.3 to 85.2% of
      nucleotide sequence and 85.4 to 89.3% of deduced amino acid sequence. Thus they
      were substantially different from each other. One of them was classified as
      genotype VI/3b due to an 88.2% similarity in nucleotide sequence to that of the
      reported HCV isolates of this genotype, whereas the remaining four were
      classified into provisional genotypes 3c, 3d, 3e and 3f. These HCV variants have
      evolved and remained in Nepal, and have not been observed in the other areas of
      the world.

PMID- 8151308
TI  - Role of virion M2 protein in influenza virus uncoating: specific reduction in the
      rate of membrane fusion between virus and liposomes by amantadine.
AB  - The anti-influenza virus drug amantadine was shown to reduce the rate of fusion
      of liposomes with influenza A viruses whose replication is inhibited by this
      drug. The fusion with amantadine-resistant viruses was unaffected. Experiments
      with reassortant and mutant viruses showed that this effect was linked to the M2
      protein and not to the haemagglutinin of the virus. The proton ionophore
      monensin, on the other hand, substantially increased the rate of fusion of the
      viruses tested. These results indicate that the kinetics of virus-liposome fusion
      can be modulated by the virus M2 protein, the target of amantadine action, and it
      is postulated that the M2 ion channel functions by transporting protons into the
      virion interior and facilitating virus uncoating.

PMID- 8151309
TI  - Electron paramagnetic resonance and difference ultraviolet studies of Mn2+
      binding to serum transferrin.
AB  - Serum transferrin is the mammalian protein whose normal function is to transport
      ferric ions through the blood among sites of absorption, storage, and
      utilization. It has two specific metal-binding sites that bind a variety of metal
      ions in addition to ferric ion. The macroscopic equilibrium constant for the
      binding of the first equivalent of Mn2+ to apotransferrin has been determined by
      electron paramagnetic resonance spectroscopy (EPR) to be logKM1 = 4.06 +/- 0.13
      at pH 7.4 in 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (Hepes).
      An equilibrium constant for nonspecific binding of Mn2+ to apotransferrin of
      logKns = 2.93 +/- 0.13 has also been obtained by using EPR. Binding of Mn2+ to
      apotransferrin and to both C- and N-terminal nonferric transferrin has also been
      studied by difference UV spectroscopy. The second stepwise macroscopic
      equilibrium constant for the formation of Mn2Tf is logKM2 = 2.96 +/- 0.13. The
      site-specific microconstants for Mn2+ binding are logkN = 3.13 +/- 0.09 for the N
      terminal site and logkC = 3.80 +/- 0.09 for the C-terminal site. There does not
      appear to be any significant cooperativity between the two sites with respect to
      metal binding. An equilibrium model for the speciation of Mn2+ in serum has been
      developed which estimates that almost 90% of Mn2+ is bound to serum proteins, but
      only approximately 1% is bound to transferrin. The weak binding of Mn2+ to
      apotransferrin and the obvious inability of transferrin to compete with albumin
      indicates that the appearance of Mn-transferrin as a major serum species in vivo
      must involve oxidation of the metal to form the much more stable Mn(3+)
      transferrin complex. The computer model confirms that albumin has a sufficient
      binding affinity to complex most of the Mn(II) in serum in competition with the
      common low molecular weight ligands in serum. However, there is insufficient data
      to rule out the possibility that some other protein, such as alpha 2
      macroglobulin, may compete with albumin for Mn(II).

PMID- 8151310
TI  - Synthesis and antitumor activity of 1,2-diaminocyclohexane platinum(IV)
      complexes.
AB  - The synthesis, characterization, and antitumor activity of a series of
      platinum(IV) complexes of the type DACH-PtIV(X)2Y (where DACH = trans-dl, or
      trans-l-1,2-diaminocyclohexane, X = OH or Cl, and Y = oxalato, malonato,
      methylmalonato, tartronato, ketomalonato, 1,1-cyclopropanedicarboxylato, or 1,1
      cyclobutanedicarboxylato, are described. These complexes have been characterized
      by elemental analysis, HPLC, and infrared and 195Pt NMR spectroscopic techniques.
      The complexes had good in vitro cytotoxic activity (IC50 = 0.14-7.6
      micrograms/ml) and were highly active in vivo against leukemia L1210 cells (%T/C
      = 152- > 600, cisplatin = 218). In addition, excellent in vivo antitumor
      activities against B16 melanoma (%T/C = 309), M5076 reticulosarcoma (100% cures)
      and cisplatin-resistant L1210/DDP (%T/C = 217) cell lines were also exhibited by
      an analog selected for further evaluation.

PMID- 8151311
TI  - Organomercury(II) complexes of kojic acid and maltol: synthesis,
      characterization, and biological studies.
AB  - A number of organomercury(II) complexes of kojic acid (HL1, I) and maltol (HL2,
      II) of the type p-XC6H4HgL1 (III) and p-XC6H4HgL2 (IV) [X = Me, MeO, NO2] have
      been synthesized and characterized. [formula: see text] Conductance measurements
      indicate the nonelectrolyte behavior of the complexes. From IR and UV studies,
      the bonding modes of the ligands to the organomercury(II) moieties have been
      elucidated. The 1H and 13C NMR spectra support the stoichiometry of the
      complexes. The fragmentation pattern has been analyzed on the basis of mass
      spectra. From thermal studies (TG and DTA), various kinetic and thermodynamic
      parameters for thermal degradation have been enumerated. The complexes have been
      screened against some pathogenic bacterial strains. The bactericidal activity has
      been correlated with the thermal data.

PMID- 8151312
TI  - What have we learned about risk factors for local recurrence after breast
      conserving surgery and irradiation?

PMID- 8151313
TI  - Risk factors in breast-conservation therapy.
AB  - PURPOSE: To identify clinical and pathologic factors associated with an increased
      risk of local recurrence following breast-conservation therapy (BCT) to assess
      the safety of this procedure for all subgroups of patients. PATIENTS AND METHODS:
      The study population consisted of 1,026 patients with clinical stage I and II
      breast cancer treated between 1979 and 1988 at the Netherlands Cancer Institute.
      The BCT regimen consisted of local excision and axillary lymph node dissection
      (ALND) followed by whole-breast irradiation to a total dose of 50 Gy in 2-Gy
      fractions and boost irradiation (mostly by iridium implant) of 15 to 25 Gy.
      RESULTS: With a median follow-up duration of 66 months, the actuarial breast
      recurrence rate was 4% at 5 years, counting all breast recurrences. Univariate
      analysis showed seven factors to be associated with an increased risk of local
      recurrence; age, residual tumor at reexcision, histologic tumor type, presence of
      any carcinoma-in-situ component, vascular invasion, microscopic margin
      involvement, and whole-breast radiation dose. Three factors remained
      independently significant after proportional hazard regression analysis: age,
      margin involvement, and the presence of vascular invasion. When the analysis was
      repeated, but counting only those breast recurrences that occurred before
      regional or distant failures, only young age and vascular invasion were
      independent predictive factors. In the third analysis, factors predicting the
      necessity of local salvage treatment were analyzed. In this analysis, the
      possible bias in the former analysis caused by censoring actuarial methods was
      avoided. The results were the same as in the second analysis, showing young age
      and vascular invasion as the only independent predictive factors. Breast
      recurrence rates were 6% for patients less than 40 years of age and 8% for
      patients with tumors showing vascular invasion. In the absence of risk factors,
      the breast recurrence rate is only 1% at 5 years. CONCLUSION: Slightly higher
      recurrence rates were found in patients less than 40 years of age and in patients
      with tumors showing vascular invasion. The role of margin involvement is
      uncertain.

PMID- 8151314
TI  - Effects of interleukin-1 alpha on carboplatin-induced thrombocytopenia in
      patients with recurrent ovarian cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical safety and
      ability of interleukin-1 alpha (IL-1 alpha) to ameliorate carboplatin-induced
      thrombocytopenia and thus allow patients with ovarian cancer to receive multiple
      cycles of chemotherapy at full doses. PATIENTS AND METHODS: IL-1 alpha was
      administered by continuous intravenous infusion daily at doses of 0.1 to 10
      micrograms/m2/24 hours over 4 days (96 hours) before the first cycle and/or
      following the second cycle of carboplatin in 21 patients with recurrent ovarian
      cancer who had platinum-responsive disease. In cycle no. 1, patients received
      carboplatin (400 mg/m2) alone, while in cycle no. 2 carboplatin was followed by
      IL-1 alpha. RESULTS: Treatment with IL-1 alpha before carboplatin was associated
      with moderate leukocytosis (baseline mean, 6.15 x 10(3)/microL; maximum mean,
      17.9 x 10(3)/microL; P < .001) and significant increases in platelet counts
      (baseline mean, 241 x 10(3)/microL; maximal mean, 392 x 10(3)/microL; P < .001).
      IL-1 alpha following carboplatin significantly reduced the duration of
      thrombocytopenia (days platelet count < 50,000, 5.1 to 2.9 days; P = .003) and
      increased the area under the curve (AUC) of platelets as a function of time (P <
      .001). The mean nadir platelet counts were 54,000/microL and 67,000/microL (P =
      .08) in cycles no. 1 and 2, respectively. In fact, seven of 12 patients given 3
      micrograms/m2/d of IL-1 alpha had less thrombocytopenia in cycle no. 2 than in
      cycle no. 1. Treatment with IL-1 alpha was associated with the tolerance of
      multiple cycles of carboplatin at the same dose in several patients. The maximum
      tolerated dose (MTD) was 3 micrograms/m2/d; fever, chills, hypotension, and fluid
      retention were dose-limiting toxic effects. CONCLUSION: These findings
      demonstrate that IL-1 alpha can enhance recovery of platelets following
      carboplatin therapy and suggest a potential therapeutic role for IL-1 alpha in
      attenuating thrombocytopenia associated with chemotherapy.

PMID- 8151315
TI  - Effects of PIXY321, a granulocyte-macrophage colony-stimulating
      factor/interleukin-3 fusion protein, on chemotherapy-induced multilineage
      myelosuppression in patients with sarcoma.
AB  - PURPOSE: To evaluate the clinical safety and ability of PIXY321, a novel fusion
      protein of recombinant human granulocyte-macrophage colony-stimulating factor (GM
      CSF) and interleukin-3 (IL-3), to ameliorate chemotherapy-induced multilineage
      myelosuppression. PATIENTS AND METHODS: PIXY321 was administered by subcutaneous
      injection twice daily (25 to 1,000 micrograms/m2/d) over 14 days to 24
      chemotherapy-naive patients with sarcoma in a phase I/II study. Three weeks from
      the initiation of PIXY321, the first cycle of chemotherapy with cyclophosphamide,
      doxorubicin, and dacarbazine (DTIC) (CyADIC) was administered over 3 days. Four
      weeks later, a second cycle of CyADIC was administered, followed by 14 days of
      PIXY321. RESULTS: Treatment with PIXY321 was well tolerated. Local skin reactions
      and constitutional symptoms were the main side effects. The dose-limiting
      toxicity was not encountered; however, headache and fatigue were more frequent at
      the highest dose (1,000 micrograms/m2). PIXY321 before chemotherapy elicited a
      modest increase in the WBC count (consisting mainly of mature neutrophils),
      platelets, and corrected reticulocyte counts (all P < .001). Following
      chemotherapy, PIXY321 at effective doses (500 to 1,000 micrograms/m2/d),
      significantly reduced both the degree (mean nadir, 70 v 310/microL; P = .016) and
      duration (mean days < 500/microL, 6.6 v 3.9 days; P = .002) of neutropenia.
      Cumulative thrombocytopenia was not observed during the first two cycles of
      CyADIC (mean nadir platelet count, 103 v 95 x 10(3)/microL, in cycles no. 1 and
      2, respectively; P = NS). Compared with our historic control data, the mean nadir
      platelet count in cycle no. 2 was significantly higher after PIXY321 (1.7-fold, P
      < .05) than with CyADIC alone or with GM-CSF support. There was a suggestion for
      a dose response, since the mean percentage change in nadir platelet values from
      cycle no. 1 to cycle no. 2 increased with the PIXY321 dose (P < .02), with the
      peak effect observed at 750 micrograms/m2/d. CONCLUSION: These results suggest a
      potential clinical role for PIXY321 in attenuating the cumulative multilineage
      hematopoietic toxicity of chemotherapy.

PMID- 8151316
TI  - Tumor epidermal growth factor receptor studies in patients with non-small-cell
      lung cancer or head and neck cancer treated with monoclonal antibody RG 83852.
AB  - PURPOSE: Tumor tyrosine kinase activity associated with the epidermal growth
      factor receptor (EGFR) and localization of anti-EGFR monoclonal antibody RG 83852
      were studied in patients with non-small-cell lung cancer (NSCLC) and head and
      neck cancer. PATIENTS AND METHODS: Fifteen patients were treated with escalating
      doses of RG 83852 by continuous intravenous infusion for 5 days. Fresh tumor
      specimens were obtained 24 hours after therapy in 10 patients (of whom five had a
      pretherapy sample taken). Tumor EGFR tyrosine kinase activity was determined in
      fresh tumor samples by autophosphorylation of EGFR isolated in immunocomplexes
      with RG 83852. Tumor EGFR saturation with RG 83852 was assessed
      semiquantitatively by comparing the EGFR tyrosine kinase activity in
      immunocomplexes of tumor specimens obtained after therapy with total EGFR
      tyrosine kinase activity assessed by exogenous addition of RG 83852 to tumor
      lysates. Modulation of EGFR tyrosine kinase activity after the administration of
      RG 83852 was assessed by comparing EGFR tyrosine kinase activity from the same
      malignant lesion obtained before and after therapy. Tumor localization of RG
      83852 and EGFR saturation were also assessed by immunohistochemistry. RESULTS: No
      significant side effects were observed up to a total dose of 600 mg/m2. Based on
      tyrosine kinase activity, a high degree of EGFR saturation (> or = 50%) was
      observed at doses > or = 200 mg/m2, and EGFR saturation was estimated to be 100%
      at a dose level of 600 mg/m2 both in tumor tissue and skin used as surrogate EGFR
      positive tissue. Immunohistochemistry studies showed that RG 83852 localized in
      tumor tissue and skin, but not in stroma, at doses > or = 400 mg/m2, and high
      EGFR saturation was observed at 600 mg/m2. Tumor EGFR tyrosine kinase activity
      was studied in five patients (four with EGFR-positive tumors) before and 24 hours
      post-therapy; a threefold to fourfold upregulation of EGFR tyrosine kinase
      activity in posttherapy specimens was observed in two patients. Moderate
      upregulation of EGFR itself was suggested in both of these patients and in two
      additional patients by immunohistochemistry. CONCLUSION: RG 83852 causes no toxic
      effects at doses that result in high tumor EGFR saturation. Treatment with RG
      83852 may enhance EGFR tyrosine kinase activity and/or EGFR expression. Because
      high EGFR expression by tumors has been associated with increased sensitivity to
      cytotoxic therapy, the suggestion of antibody-mediated upregulation of EGFR by
      agents such as RG 83852 may prove useful in enhancing chemotherapeutic efficacy.

PMID- 8151317
TI  - Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber
      Cancer Institute/Children's Hospital Acute Lymphoblastic Leukemia Consortium
      Protocol 85-01.
AB  - PURPOSE: The goals of this treatment program were as follows: to improve event
      free survival (EFS) rates for high-risk (HR) patients by increasing the intensity
      of induction treatment; to improve EFS rates for infants by adding a special
      postinduction intensification; to treat the CNS using cranial irradiation doses
      that were lower than in our historic control group; and to confirm our previously
      obtained good results for children with T-cell disease. PATIENTS AND METHODS: Two
      hundred twenty children with acute lymphoblastic leukemia (ALL) from all risk
      groups, including infants and patients with T-cell disease, were treated between
      1985 and 1987 with multiagent chemotherapy and cranial irradiation. RESULTS: The
      7-year EFS rate (+/- SE) for all 220 patients was 78% +/- 3% at a median follow
      up duration of 6.2 years, 89% +/- 4% for the 82 patients classified as standard
      risk (SR), and 72% +/- 4% for the remaining 138 patients classified as HR and
      very high risk (VHR). Eleven infants had an EFS rate of 55% +/- 15% that might be
      attributable to treatment with high doses of methotrexate and cytarabine (ara-c).
      Twenty children with T-cell disease had an EFS rate of 70% +/- 10%. CNS leukemia
      relapse (isolated or combined with bone marrow) occurred in four of 82 SR
      patients who received 18 Gy of cranial irradiation and four of 138 HR and VHR
      patients who received 24 Gy. CONCLUSION: This protocol, which featured early
      intensive treatment including asparaginase, doxorubicin, and cranial irradiation,
      provided good long-term disease control for children with ALL.

PMID- 8151318
TI  - Autologous and allogeneic bone marrow transplantation for chronic lymphocytic
      leukemia: preliminary results.
AB  - PURPOSE: This study was undertaken to evaluate the feasibility and therapeutic
      effect of high-dose chemoradiotherapy with autologous or allogeneic bone marrow
      transplantation (BMT) in patients with advanced chronic lymphocytic leukemia
      (CLL) who relapse after fludarabine treatment. PATIENTS AND METHODS: Twenty-two
      patients with advanced CLL received high-dose cyclophosphamide, total-body
      irradiation, and BMT. Eleven patients with relapsed CLL received autologous BMT
      with marrow collected during a prior fludarabine-induced remission; leukemia
      cells were depleted from the autologous marrow in seven patients using an anti
      CD19 monoclonal antibody and immunomagnetic separation. Eleven patients received
      allogeneic or syngeneic BMT, seven of whom had refractory Rai stage III or IV
      disease. RESULTS: Six autologous transplant recipients achieved a complete
      remission (CR), four a nodular CR (nCR), and one a partial remission (PR). Two
      recurred with CLL, and three developed Richter's transformation. Two patients had
      recurrence of immune cytopenias while in morphologic remission; one of these
      patients died of cytomegalovirus pneumonia. Six of 11 patients survive in
      remission 2 to 29 months following BMT. Of the 11 patients who received
      allogeneic or syngeneic BMT, seven achieved a CR, two a nCR, and one a PR; 10
      survive 2 to 36 months following BMT. CONCLUSION: These data indicate that high
      dose chemotherapy with allogeneic BMT is effective at producing CRs in patients
      with CLL. Autologous transplantation in CLL is feasible and is capable of
      producing remissions in patients with advanced CLL. Further studies are warranted
      to assess the role of BMT in the treatment of CLL.

PMID- 8151319
TI  - High-dose melphalan and autologous bone marrow transplantation as consolidation
      in previously untreated myeloma.
AB  - PURPOSE: We report the results of intensive chemotherapy with high-dose melphalan
      (HDM) following conventional-dose cytoreductive chemotherapy in previously
      untreated patients with myeloma. PATIENTS AND METHODS: From 1986 to 1991, 53
      previously untreated patients with myeloma received HDM 200 mg/m2 plus
      methylprednisolone 1.5 g daily (MP) for 5 days with autologous bone marrow
      transplantation (ABMT) after cytoreductive chemotherapy. RESULTS: At the time of
      HDM administration, responses to induction therapy were complete remission (CR)
      in nine patients, partial remission (PR) in 38, and no response (NR) in six.
      Following HDM, all but one patient responded, with 40 patients achieving a CR
      (75%). There was one treatment-related death following HDM. The median time to
      reach a WBC count more than 1,000/microL and platelet count more than
      25,000/microL was 19 days (range, 13 to 30) and 24 days (range, 15 to 55),
      respectively. The median duration of response has not been reached at 20 months,
      and it is significantly longer for patients in CR than for those in PR (P <
      .025). Currently, with a median follow-up duration of 31 months (range, 6 to 58),
      12 patients are dead and 40 are alive, and the estimated probability of survival
      at 54 months is 63%. Multivariate analysis found hemoglobin (Hb) more than 10
      g/dL (P = .012), and stage A disease (P = .001) at diagnosis to be favorable
      indicators for survival. CONCLUSION: Myeloma patients who are able to receive HDM
      plus ABMT following conventional chemotherapy achieve a high proportion of CRs,
      which may be associated with prolonged survival.

PMID- 8151320
TI  - High-dose melphalan for multiple myeloma: long-term follow-up data.
AB  - PURPOSE: To present long-term follow-up data of patients with myeloma treated
      with high-dose melphalan HDM, including an assessment of prognostic factors.
      PATIENTS AND METHODS: Between November 1981 and April 1986, 63 previously
      untreated patients with multiple myeloma received HDM 140 mg/m2 without
      autologous bone marrow transplantation. RESULTS: The overall response rate was
      82% (51 of 62), with 32% (20 of 62) patients entering complete remission (CR).
      The median duration of response was 18 months, and six patients remain alive and
      free from disease progression at 60+ to 84+ months. Improvements in quality of
      life associated with remission were immediate in terms of pain grade (89% of
      patients) and performance status (92%), and later in terms of bone healing (29%).
      Currently, at a median follow-up duration of 74 months (range, 63 to 100) since
      HDM, 23 patients are alive with a median survival duration of 47 months, and 35%
      of patients are expected to be alive at 9 years. Apart from early-stage disease,
      no factors were found to predict long-term survival. No second malignancies or
      other late side effects have been recorded. CONCLUSION: Single-agent HDM without
      autologous bone marrow transplantation is a feasible therapeutic option in
      myeloma, and is associated with a high objective response rate, relatively long
      remission durations, and good symptom control.

PMID- 8151321
TI  - Serum levels of soluble CD30 are elevated in the majority of untreated patients
      with Hodgkin's disease and correlate with clinical features and prognosis.
AB  - PURPOSE: To evaluate the serum levels of the soluble form of the CD30 molecule
      (sCD30) in patients with Hodgkin's disease (HD) to establish whether there is a
      correlation with clinical features at presentation and prognosis. PATIENTS AND
      METHODS: The sCD30 serum levels of 117 patients were measured at diagnosis with a
      commercial sandwich enzyme-linked immunoadsorbent assay (ELISA) test kit, and in
      78 of these patients the sCD30 levels were also recorded during the follow-up
      period. RESULTS: sCD30 levels at diagnosis were increased (> 20 U/mL) in a high
      proportion of patients (87.2%; mean +/- SD, 108 +/- 134 v 5.3 +/- 5.7 U/mL in
      controls, P < .0001) and correlated with stage (stages I + II, 73 +/- 97 U/mL;
      III + IV, 162 +/- 165 U/mL; P < .0001), with presence of B symptoms (stage A, 69
      +/- 82 U/mL; stage B, 162 +/- 171 U/mL; P < .0001), and, to some extent, with
      tumor burden (bulky presentation, 141 +/- 129 U/mL; nonbulky, 91 +/- 133 U/mL; P
      = .058). Patients with sCD30 levels greater than 100 U/mL at diagnosis had a
      significantly higher rate of poor outcome in terms of failure to achieve a
      complete remission (CR) or disease relapse after CR achievement. In fact, the
      event-free survival (EFS) duration of patients with sCD30 levels greater than 100
      U/mL was significantly worse (P = .0016). Using multivariate analysis, an sCD30
      level greater than 100 U/mL retained its significance after adjustment for other
      prognostic parameters. CONCLUSION: sCD30 in HD at presentation strictly
      correlates with clinical features. Serum levels greater than 100 U/mL at
      diagnosis entail a significantly higher risk of treatment failure, a factor that
      is independent of other prognostic parameters.

PMID- 8151322
TI  - Detection of cells bearing the t(14;18) translocation following myeloablative
      treatment and autologous bone marrow transplantation for follicular lymphoma.
AB  - PURPOSE: To use the polymerase chain reaction (PCR) technique for molecular
      assessment of the results of myeloablative treatment of follicular lymphoma with
      autologous bone marrow transplantation. PATIENTS AND METHODS: Seventy-six
      patients with follicular or transformed follicular lymphoma were treated with
      cyclophosphamide 60 mg/kg x 2 and total-body irradiation 12 Gy, supported by
      autologous bone marrow transplantation. The bone marrow mononuclear cell fraction
      was treated in vitro with CD20 monoclonal antibody and baby rabbit complement.
      The PCR technique was used to identify 50 patients with amplifiable t(14; 18)
      translocations in biopsy material from lymph nodes or bone marrow infiltrated by
      lymphoma. RESULTS: Following treatment of the harvested bone marrow in vitro, 29
      samples were tested by PCR to assess the efficacy of purging. In 25 cases, the
      same t(14; 18) sequences were amplified as from the patients' original biopsies,
      while in four cases, the marrow became PCR-negative. Three of the four patients
      treated with PCR-negative marrow subsequently developed recurrent lymphoma,
      compared with 11 of 25 in the PCR-positive group. Bone marrow and peripheral
      blood mononuclear cell samples from 27 patients were studied during the follow-up
      period. All but one had the presence of the lymphoma-related t(14; 18) clone
      detectable by PCR and confirmed by direct sequencing from at least one sample
      between 3 months and 7 years after reinfusion of the bone marrow. With a median
      follow-up duration of 3 years, 13 patients developed recurrent disease, 13
      remained in remission with the t(14; 18) still detectable, and one died of acute
      myeloid leukemia. CONCLUSION: This form of therapy does not eliminate the
      lymphoma-related t(14; 18)-bearing clone of cells, although the significance of
      its continued presence is uncertain. Improved methods for both treatment of the
      bone marrow in vitro and treatment of the lymphoma in vivo are required.

PMID- 8151324
TI  - Evaluation of the neurobehavioral functioning of patients before, during, and
      after bone marrow transplantation.
AB  - PURPOSE: To evaluate the cognitive and emotional functioning of patients
      undergoing bone marrow transplantation (BMT) in the protected environment (PE).
      PATIENTS AND METHODS: Patients were given tests of cognition and mood before
      their hospitalization in the PE, after 2 weeks, at discharge, and at 8 months
      post-BMT. Locus of control, degree of social support, previous biotherapy, and on
      treatment psychiatric consultation were also analyzed. RESULTS: Before BMT, 20%
      of patients had mild cognitive dysfunction, and nearly 40% had significant
      anxiety. Although few patients developed problems with cognition or mood during
      the study, short-term memory deficits nearly doubled at follow-up compared with
      baseline. Anxiety decreased significantly during hospitalization and remained low
      at follow-up. In contrast, depression increased throughout hospitalization, but
      decreased at follow-up. Pre-BMT emotional status and cognitive functioning were
      highly related to long-term outcome. Type of BMT, locus of control, and degree of
      social support were related to psychologic distress and cognitive functioning,
      both during and after BMT. Patient age was not a predictor of neurobehavioral
      symptoms during or after BMT. CONCLUSION: Pretransplant emotional and cognitive
      functioning are important determinants of long-term outcome and quality of life
      (QOL) in BMT patients. In addition, a few patients undergoing BMT develop short
      term memory difficulties and mood disturbance that may persist. Pretransplant
      identification of patients at risk for neurobehavioral difficulties may guide
      early interventions during hospitalization. Posttransplant assessment may then be
      used to develop rehabilitation programs and other interventions for individuals
      with persisting complaints.

PMID- 8151323
TI  - Multicenter randomized trial of dacarbazine alone or in combination with two
      different doses and schedules of interferon alfa-2a in the treatment of advanced
      melanoma.
AB  - PURPOSE: Some phase II studies have suggested that the combination of interferons
      (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM)
      increases the antitumor activity of DTIC alone. In an attempt to confirm this
      hypothesis, a randomized study was performed with the further intent of observing
      whether low doses of recombinant interferon alfa-2a (rIFN alpha 2a) could be as
      effective as intermediate doses. PATIENTS AND METHODS: Two hundred sixty-six
      patients were randomized onto three different treatment arms: DTIC 800 mg/m2
      intravenously (IV) days 1 and 21; DTIC plus rIFN alpha 2a 9 mIU intramuscularly
      (IM) daily; and DTIC plus rIFN alpha 2a 3 mIU IM three times per week. Major
      prognostic factors were well balanced among the three arms. Chemotherapy was
      administered for a maximum of eight cycles. After 6 months of therapy, rIFN alpha
      2a was continued until disease progression at 3 mIU three times per week in
      responding patients who had received the combined treatment. RESULTS: The
      percentage of objective responses did not differ among the three groups (20%,
      28%, and 23%, respectively), although a significant prolongation of response
      duration was observed when rIFN alpha 2a was added to DTIC (2.6 v 8.4 v 5.5
      months, respectively). However, this improvement in response duration did not
      translate into an amelioration of overall survival. The addition of rIFN alpha 2a
      led to the onset of flu-like syndrome, but in no case was it necessary to
      withdraw the treatment program and no toxic deaths or life-threatening toxicities
      were reported. CONCLUSION: In this study, rIFN alpha 2a significantly prolonged
      response duration, whereas no effects on response rate and survival were
      observed; rIFN alpha 2a 3 mIU appeared to be equally effective and better
      tolerated than 9 mIU.

PMID- 8151325
TI  - Prediction of systemic fungal infection in allogeneic marrow recipients: impact
      of amphotericin prophylaxis in high-risk patients.
AB  - PURPOSE: To identify risk factors that might predict for systemic fungal
      infections in marrow transplant recipients within the first 100 days and to
      assess the efficacy of low-dose amphotericin B used as prophylaxis for candidemia
      and infection with invasive Aspergillus species in patients at risk. PATIENTS AND
      METHODS: A retrospective analysis of transplant outcomes for 331 allogeneic
      marrow recipients transplanted between 1983 and 1989 was performed to identify
      patients who might be at increased risk of fungal infection. Factors analyzed
      included disease, remission status, transplant regimen, graft-versus-host disease
      (GVHD) prophylaxis, duration of neutropenia, and development of GVHD. A trial of
      low-dose amphotericin (5 to 10 mg/d) begun on day +1 and continuing for 2 to 3
      months posttransplant was begun in 1987 to evaluate its utility in reducing
      systemic mycoses. RESULTS: There were 18 episodes of candidemia and 18 systemic
      mycoses documented by blood or tissue culture or by biopsy. The initiation of
      high-dose (0.5 to 1 mg/kg/d) corticosteroids early as a component of GVHD
      prophylaxis in 1986 was identified as the most important risk factor for fungal
      infections, with a sixfold increase in infections as compared with the previous
      GVHD regimen (P < .0001); this was despite a significant decrease in the
      incidence of grade II to IV GVHD (7% v 43%; P = .0001). Low-dose amphotericin B
      initiated before the start of high-dose corticosteroid GVHD prophylaxis reduced
      the incidence of fungal infections from 30% to 9% (P = .01) without renal
      toxicity. Cyclosporine levels were lower in the patients who received
      amphotericin, leading to an increase in the rate of GVHD to 19% (P = .02).
      Controlling for GVHD prophylaxis, prolonged neutropenia (P = .00), and grade II
      to IV GVHD (P = .01) were also identified as risk factors for fungal infection.
      CONCLUSION: Amphotericin B can be used in low doses as prophylaxis for fungal
      infections early in the posttransplant course. However, cyclosporine doses need
      to be monitored to maintain target levels.

PMID- 8151326
TI  - Phase I trial of doxorubicin with cyclosporine as a modulator of multidrug
      resistance.
AB  - PURPOSE: To study the effects of cyclosporine (CsA), a modulator of multidrug
      resistance (MDR), on the pharmacokinetics and toxicities of doxorubicin. PATIENTS
      AND METHODS: Nineteen patients with incurable malignancies entered this phase I
      trial. Initially patients received doxorubicin alone (60 or 75 mg/m2) as a 48
      hour continuous intravenous (i.v.) infusion. Patients whose tumors did not
      respond received CsA as a 2-hour loading dose of 6 mg/kg and a 48-hour continuous
      infusion of 18 mg/kg/d with doxorubicin. Target CsA levels were 3,000 to 4,800
      ng/mL (2.5 to 4.0 mumol/L). Doxorubicin doses were reduced to 40% of the prior
      dose without CsA, and then escalated until myelosuppression equivalent to that
      resulting from doxorubicin alone was observed. Doxorubicin pharmacokinetics were
      analyzed with and without CsA. RESULTS: Thirteen patients received both
      doxorubicin alone and the combination of doxorubicin and CsA. Mean CsA levels
      were more than 2,000 ng/mL for all cycles and more than 3,000 ng/mL for 68% of
      cycles. Dose escalation of doxorubicin with CsA was stopped at 60% of the
      doxorubicin alone dose, as four of five patients at this dose level had WBC
      nadirs equivalent to those seen with doxorubicin alone. Nonhematologic toxicities
      were mild. Reversible hyperbilirubinemia occurred in 68% of doxorubicin/CsA
      courses. The addition of CsA to doxorubicin increased grade 1 and 2 nausea (87% v
      47%) and vomiting (50% v 10%) compared with doxorubicin alone. There was no
      significant nephrotoxicity. Paired pharmacokinetics were studied in 12 patients.
      The addition of CsA increased the dose-adjusted area under the curve (AUC) of
      doxorubicin by 55%, and of its metabolite doxorubicinol by 350%. CONCLUSION: CsA
      inhibits the clearance of both doxorubicin and doxorubicinol. Equivalent
      myelosuppression was observed when the dose of doxorubicin with CsA was 60% of
      the dose of doxorubicin without CsA. Understanding these pharmacokinetic
      interactions is essential for the design and interpretation of clinical trials of
      MDR modulation, and should be studied with more potent MDR modulators.

PMID- 8151327
TI  - Attitudes about genetic testing for breast-ovarian cancer susceptibility.
AB  - PURPOSE: In anticipation of the availability of genetic testing for a breast
      ovarian cancer susceptibility gene (BRCA1), this study examined interest in and
      expectations about the impact of a potential genetic test. PATIENTS AND METHODS:
      The subjects were 121 first-degree relatives (FDRs) of ovarian cancer patients.
      The design was cross-sectional. Subjects completed a structured telephone
      interview of attitudes about cancer and genetic testing, and self-report
      psychologic questionnaires to assess coping style and mood disturbance. RESULTS:
      Overall, 75% of FDRs said that they would definitely want to be tested for BRCA1
      and 20% said they probably would. In bivariate analyses, interest was associated
      positively with education, perceived likelihood of being a gene carrier,
      perceived risk of ovarian cancer, ovarian cancer worries, and mood disturbance.
      In logistic regression analysis, perceived likelihood of being a gene carrier was
      associated strongly with interest (odds ratio, 3.7; P = .006). Results of
      stepwise linear regression modeling indicated that an anticipated negative impact
      of genetic testing was associated with being younger (beta = -.66, P = .009),
      having more mood disturbance (beta = .015, P = .01), and having an information
      seeking coping style (beta = .19, P = .002). CONCLUSION: These results suggest
      that the demand for genetic testing for BRCA1 among FDRs of cancer patients may
      be great. Moreover, those who elect to participate may represent a more
      psychologically vulnerable subgroup of high-risk women.

PMID- 8151328
TI  - Cancer chemoprevention.
AB  - PURPOSE: To review the most important recent advances in clinical trials and
      biologic studies within the growing field of chemoprevention. METHODS: The most
      critical methods issue concerns the definitive end point of phase III trials,
      which is now cancer incidence. This end point usually needs thousands of subjects
      monitored for 5 to 10 or more years to determine efficacy. Biologic markers of
      potential intermediate end points are under intensive study and may one day
      replace cancer incidence. Validated intermediate end point biomarkers could
      greatly reduce phase III trial populations, durations, and costs. RESULTS:
      Randomized clinical trials over the last 5 years have produced significant
      activity in reversing oral, skin, colon, and cervical premalignancy; in
      preventing primary skin and stomach cancer; and in preventing second primary
      tumors associated with head and neck and lung cancer. These clinical advances
      have been paralleled at the basic science level by elegant molecular studies of
      premalignant carcinogenesis and of chemopreventive agents' mechanisms of action.
      One major laboratory advance is the discovery of nuclear retinoic acid receptors
      and strong evidence of their roles both in carcinogenic progression and in its
      response to retinoids. CONCLUSION: Chemoprevention has matured greatly in recent
      years with the significant reversal or suppression of premalignancy by
      chemopreventive agents in several sites. The future of chemoprevention will be
      determined largely by several ongoing phase III trials, including trials of
      retinoids, beta-carotene, and alpha-tocopherol in the aerodigestive tract, of
      tamoxifen and fenretinide in the breast, and of finasteride in the prostate.

PMID- 8151329
TI  - Myelodysplastic syndrome and acute myeloid leukemia secondary to mitolactol
      treatment in patients with breast cancer.

PMID- 8151330
TI  - An alternative method to overcome central venous portable external infusion pump
      blockage in patients receiving weekly 24-hour high-dose fluorouracil and
      leucovorin.

PMID- 8151331
TI  - Mantle cell lymphoma.

PMID- 8151332
TI  - Meta-analysis of adjuvant chemotherapy in gastric cancer: a critical reappraisal.

PMID- 8151333
TI  - Meta-analyses need time, collaboration, and funding.

PMID- 8151334
TI  - Periapical cemental dysplasia: a case report.

PMID- 8151335
TI  - To have or to be.

PMID- 8151336
TI  - Donated dental services.

PMID- 8151337
TI  - OSHA interprets bloodborne pathogens standard.

PMID- 8151338
TI  - Reflections upon the nature and management of intracranial and intraspinal
      vascular malformations and fistulae.
AB  - Evidence is presented that dural fistulae are preceded by sinus thrombosis and
      that their danger lies in arterialized venous pressure within the cranium or the
      orbit. Arterial side occlusion leads to recurrence, while venous side occlusion
      leads to permanent cure. Vein of Galen aneurysms embrace some features of
      cerebral arteriovenous malformations (AVM's), namely a reticulum, and some
      features of dural fistulae, namely evidence of previous sinus anomaly and direct
      drainage into a sinus. These aneurysms are also permanently cured by venous side
      thrombosis, although the dangers inherent in their reticulum demand that this be
      done in stages or preceded by arterial side embolization. A very limited
      experience with venous end occlusion of cerebral (and spinal) AVM's suggests that
      they, too, can be permanently cured by venous side occlusion without excision.
      Their reticulum demands maximum, multistage, preliminary arterial side
      embolization together with intraoperative hypotension during the venous occlusion
      stage in order to minimize intracerebral hemorrhage or swelling. Schematic models
      of both fistulae and malformations are presented, together with reasons why
      particulate embolization is safer than glue embolization. The theory is advanced
      that dural fistulae, vein of Galen aneurysms, and AVM's are venous- rather than
      arterial-based lesions, which is consistent with the experience that permanent
      cure has been effected by venous side occlusion without excision in all three
      anomalies. It is speculated that there may be a developmental link between AVM
      and the venous malformation, the AVM being essentially a fistulized venous
      malformation.

PMID- 8151339
TI  - Treatment of cranial dural arteriovenous fistulae by interruption of
      leptomeningeal venous drainage.
AB  - Cranial dural arteriovenous fistulae (AVF's) of the tentorial incisura or the
      dura of the middle fossa have a much higher incidence of draining via
      leptomeningeal veins than do AVF's of the transverse-sigmoid sinuses or the
      cavernous sinus. Such a drainage pattern is associated with an increased
      incidence of intracranial hemorrhage and progressive focal neurological deficits.
      Patients with cranial dural AVF's often undergo surgical excision and/or
      endovascular embolization for elimination of the AVF. Since these lesions are
      frequently large and involve the skull base or adjacent dural sinuses, extensive
      surgery is often required. In contrast, spinal dural AVF's with only intradural
      venous drainage to the medullary venous system are treated successfully by simply
      interrupting the vein that drains the dural AVF as it enters the subarachnoid
      space. The authors identified a subgroup of patients with cranial dural AVF's in
      whom the AVF was drained only by leptomeningeal veins, and sought to establish
      whether simple interruption of the vein draining the blood from the AVF into the
      subarachnoid space is effective and lasting treatment in this subgroup of
      patients, as it is in patients with spinal dural AVF's. Four adult patients with
      symptomatic cranial dural AVF's (two petrotentorial, one middle fossa floor, and
      one posterior fossa base) were identified on arteriography as having fistulae
      that were supplied by the internal and/or external carotid arteries and drained
      only via leptomeningeal veins (two entered the petrosal vein, one a cerebellar
      hemispheric vein, and one a mesencephalic vein). All patients underwent
      interruption of the vein draining the dural AVF as it penetrated the dura to
      enter the subarachnoid space, and experienced neurological improvement after
      surgery. Repeat arteriography at 1 to 2 weeks (three patients), 3 months (3
      patients), 12 to 15 months (three patients), and 4 years (two patients) revealed
      no residual AVF and no evidence of abnormal blood flow. Many cranial dural AVF's
      with leptomeningeal venous drainage (the type with the most aggressive behavior)
      are drained only by leptomeningeal veins. This subgroup of patients can be
      identified by selective arteriography and requires only interruption of the
      draining vein as it enters the subarachnoid space for successful, lasting
      elimination.

PMID- 8151340
TI  - Feeding artery pedicle aneurysms: association with parenchymal hemorrhage and
      arteriovenous malformation in the brain.
AB  - The association between arteriovenous malformations (AVM's) and aneurysms is well
      documented in the literature. However, a specific type of aneurysm, termed a
      "pedicle" aneurysm, has received little attention despite its role as a primary
      source of hemorrhage. The authors report four recent cases of patients with
      cerebral AVM's who bled from aneurysms arising from the midportion of AVM-feeding
      artery pedicles. Angiography, computerized tomography, and magnetic resonance
      imaging confirmed the origin of the hemorrhage from the pedicle aneurysm in each
      case. Because pedicle aneurysms are at risk for recurrent rupture, they represent
      an important subclassification of aneurysms associated with AVM's. The authors
      have expanded the previous classification systems for aneurysms associated with
      AVM's to include pedicle aneurysms; this classification is based on the location
      of the aneurysm and its relationship to the malformation. Complete documentation
      of such aneurysms as the potential source of hemorrhage is recommended, and
      prompt intervention by embolization and/or surgical resection is indicated for
      this dangerous aneurysm associated with cerebral AVM's.

PMID- 8151341
TI  - Multiple clipping technique for large and giant internal carotid artery aneurysms
      and complications: angiographic analysis.
AB  - Experience with surgical clipping of 16 large and nine giant aneurysms of the
      intradural internal carotid artery (ICA) is described. Reconstruction of the
      parent artery with part of the aneurysmal wall was necessary in the majority of
      cases. Multiple clips were required for satisfactory clipping in 20 cases.
      Complications related to the clipping procedure comprised occlusion and stenosis
      of the parent carotid artery in isolated cases. Straightening of the parent
      carotid artery with consequent kinking of the middle cerebral artery was seen in
      three cases of an aneurysm with a dome directed ventrally in the proximal segment
      of the ICA. The factors that caused straightening of the ICA are analyzed. It was
      observed that an excessive change in the direction of the ICA can cause cerebral
      infarction.

PMID- 8151342
TI  - Early surgery for ruptured vertebrobasilar aneurysms.
AB  - The authors present a series of 1767 patients with aneurysms of the
      vertebrobasilar circulation, most of whom were operated on 14 days or more
      following their last subarachnoid hemorrhage (SAH). Since 1970, 206 patients with
      vertebrobasilar aneurysms have been surgically treated within 7 days after their
      last SAH (day of SAH = Day 0). Of patients with a good preoperative grade
      (Botterell Grade 1 or 2), a good or excellent outcome was obtained in 80% during
      the first postsurgical month, irrespective of the timing of surgery. All except
      one of the Grade 5 patients died, and 70% of the Grade 4 patients were
      significantly disabled or dead. The overall operative mortality rate was the same
      whether surgery took place in the 1st week after SAH or was delayed. The
      frequency of rupture of the aneurysm during early surgery was not higher than
      during late surgery. Thirteen percent of patients developed a delayed ischemic
      neurological deficit as a consequence of reactive arterial narrowing (vasospasm).
      The authors recommend early surgery for patients with a good preoperative grade,
      whose aneurysm does not present a particular technical difficulty because of
      size, configuration, or location, and occasionally in patients whose lives appear
      to be in jeopardy because of recurrent hemorrhage.

PMID- 8151343
TI  - Surgery for paraclinoidal carotid artery aneurysms.
AB  - Aneurysms arising from the proximal carotid artery between the roof of the
      cavernous sinus and the origin of the posterior communicating artery pose
      conceptual and technical surgical problems with regard to acquisition of proximal
      control and safe intracranial exposure. Over the past 3 1/2 years, 89 patients
      with paraclinoidal aneurysms have been treated at the University of Texas
      Southwestern Medical Center. Thirty-nine (44%) of these patients presented with
      subarachnoid hemorrhage. A total of 149 aneurysms and six arteriovenous
      malformations have been identified in this patient group such that 38 (43%) of
      the patients suffered multiple vascular anomalies. Temporary artery occlusion has
      been employed during operation in 48 cases (54%), permanent carotid artery
      occlusion in four (4%), and hypothermic circulatory arrest in two (2%). Twenty
      two patients harbored giant aneurysms, seven of which had ruptured. Outcome was
      considered good in 77 patients (86.5%), fair in eight (9%), and poor in three
      (3%); one patient died. This concentrated experience permitted a practical
      anatomical grouping of aneurysms into three types: carotid-ophthalmic artery
      aneurysms with a superior or superomedial projection (44 cases); superior
      hypophyseal aneurysms with a medial or inferomedial projection (26 cases); and
      proximal posterior carotid artery wall aneurysms projecting posteriorly or
      posterolaterally (19 cases). Despite the fact that paraclinoidal aneurysms often
      disobey the traditional teachings of aneurysm development, having no vessel of
      origin or clear hemodynamic cause, this practical grouping has allowed
      individualized and focused operative approaches unique to each aneurysm
      projection with good visual function and outcome in most patients.

PMID- 8151344
TI  - The efficacy of endosaccular aneurysm occlusion in alleviating neurological
      deficits produced by mass effect.
AB  - Endovascular obliteration of intracranial aneurysms with preservation of the
      parent artery (endosaccular occlusion) has been advocated for patients who fail
      or are excluded from surgical clipping and cannot undergo Hunterian ligation
      therapy. To clarify the effect that endosaccular occlusion has on the presenting
      neurological signs, 26 patients with aneurysms and symptoms related to mass
      effect who underwent this therapy were followed for a mean of 60 months. Only
      patients with objective neurological deficits who had not suffered a hemorrhage
      were included in this series. Response to therapy was classified into one of
      three groups: "resolved," if the patient had complete resolution of presenting
      signs; "improved," if significant and sustained improvement was recorded in the
      neurological examinations, and "unchanged," if no change was observed. Thirteen
      patients (50%) were classified as resolved, 11 (42.3%) as improved, and two
      (7.7%) as unchanged. A comparison of patients classified as resolved with those
      who were improved revealed that the former group had less wall calcification (30%
      vs. 60%) and a shorter duration of symptoms. Patients with neurological sign
      resolution (62%) were more likely to have totally occluded aneurysms on late
      follow-up arteriograms than those who had improvement (28%) or were unchanged
      (0%). This study suggests that endosaccular embolization therapy can improve or
      alleviate presenting neurological signs unrelated to hemorrhage or distal
      embolization in the majority of cases.

PMID- 8151345
TI  - Nonsurgical treatment of unruptured intracranial vertebral artery dissection with
      serial follow-up angiography.
AB  - The question of whether unruptured intracranial vertebral artery dissections
      should be treated surgically or nonsurgically still remains unresolved. In this
      study, six consecutive patients with intracranial vertebral artery dissection
      presenting with brain-stem ischemia without subarachnoid hemorrhage (SAH) were
      treated non-surgically with control of blood pressure and bed rest, and five
      received follow-up review with serial angiography. No further progression of
      dissection or associated SAH occurred in any of the cases, and all patients
      returned to their previous lifestyles. In the serial angiograms in five patients,
      the findings continued to change during the first few months after onset. Four
      cases ultimately showed "angiographic cure," while fusiform aneurysmal dilatation
      of the affected vessel persisted in one case. In one patient, arterial dissection
      was visualized on the second angiogram despite negative initial angiographic
      findings. These results indicate that intracranial vertebral artery dissection
      presenting without SAH can be treated nonsurgically, with careful angiographic
      follow-up monitoring. Persistent aneurysmal dilatation as a sequela of arterial
      dissection seemed to form a subgroup of fusiform aneurysms of the posterior
      circulation. These aneurysms may be prone to late bleeding and may require
      surgical treatment.

PMID- 8151346
TI  - Diffuse brain swelling after head injury: more often malignant in adults than
      children?
AB  - A series of 118 patients with diffuse traumatic brain swelling was studied
      retrospectively in order to compare the clinical findings in children with those
      in adults, and to determine the occurrence of neurological deterioration and
      outcome. The computerized tomography (CT) picture of absent third ventricle and
      basal cisterns was used to identify the cases. Although this condition has been
      associated with children, we found the same number of children and adults (59
      cases each). Secondary deterioration (decline in consciousness, the development
      of new focal neurological signs, or an increase in intracranial pressure)
      occurred in 40% of cases and was more common in adults than children. Features
      that were significantly associated with deterioration were the presence of
      prolonged coma (> 1 hour) after the injury, CT signs of diffuse axonal injury or
      subarachnoid hemorrhage, or a recorded episode of hypotension. A moderate or good
      recovery at 6 months was achieved by 70 patients (59%), but 45 patients had a
      poor outcome (severe disability in nine, vegetative state in three, and death in
      33) and this was often a consequence of secondary deterioration. In three
      patients, the outcome was not known. The combination of a severe initial injury,
      secondary insult, and diffuse swelling is associated with a poor outlook,
      particularly in adults. The CT appearance of diffuse swelling may develop more
      readily in children because of the lack of cerebrospinal fluid available for
      displacement. In children, diffuse swelling may have a relatively benign course
      unless there is a severe primary injury or a secondary hypotensive insult.

PMID- 8151347
TI  - The long-term outcome in children with late-onset aqueductal stenosis resulting
      from benign intrinsic tectal tumors.
AB  - Benign intrinsic tumors arising in the dorsal midbrain have long been recognized
      as a potential cause of late-onset aqueductal stenosis. Where histopathological
      studies of such lesions have been performed, the majority have been reported to
      be low-grade gliomas. Because these tumors often present with a paucity of
      neurological findings and a characteristic radiographic appearance and because
      there has been substantial uncertainty regarding their potential for long-term
      progression, the authors have routinely deferred biopsy and/or radiotherapy for
      these lesions until there has been clear-cut evidence of disease progression.
      Herein, the authors report their experience with 16 children manifesting this
      syndrome who were treated between 1979 and 1992. The patients ranged in age from
      6 months to 14 years at presentation (median 9.75 years). In general, symptoms of
      increased intracranial pressure developed insidiously; three of the older
      children had exhibited profound macrocephaly since infancy, which predated the
      onset of other symptoms of hydrocephalus by several years. Only one of the 16
      children showed evidence of brain-stem dysfunction at presentation, a partial
      Parinaud's syndrome that resolved following placement of a ventriculoperitoneal
      shunt. In 12 patients, the tumor was detected by magnetic resonance (MR) imaging
      at initial evaluation as a bulbous enlargement of the tectal plate. In four
      patients who presented before the advent of MR imaging, initial computerized
      tomography (CT) scans failed to delineate the tectal lesion convincingly;
      however, subsequent MR studies clearly demonstrated the presence of an intrinsic
      tectal mass. All 16 patients underwent cerebrospinal fluid diversion initially,
      with conservative management of the tectal lesion and close long-term follow-up
      monitoring. Four children ultimately demonstrated clinical signs of progressive
      tumor growth with the insidious onset of partial or complete Parinaud's syndrome,
      despite the presence of a functioning shunt. The median interval to symptom
      progression was 7.8 years from the time of shunt insertion and 11.5 years from
      the onset of initial symptoms and signs of hydrocephalus. Follow-up CT and MR
      studies demonstrated obvious tumor enlargement in three of the four patients who
      then underwent stereotactic or open biopsy. The histological diagnosis in these
      three was benign mixed glioma, anaplastic astrocytoma, and low-grade astrocytoma.
      All four patients with clinical evidence of disease progression were treated with
      conventional radiotherapy; the patient with an anaplastic astrocytoma also
      received focal stereotactic radiosurgery. These patients subsequently remained
      clinically stable, with three showing tumor regression and one showing stable
      disease on serial MR studies (median follow-up period from tumor progression,
      4.25 years).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8151348
TI  - Treatment and prevention of tethered and retethered spinal cord using a Gore-Tex
      surgical membrane.
AB  - The incidence of the tethered cord syndrome after repair of spinal dysraphism is
      not insignificant. A retethered spinal cord may also develop after an untethering
      operation. In order to treat and/or prevent the tethered and retethered spinal
      cord, the authors developed and successfully used a new method in 12 cases. After
      complete release and reconstruction of the spinal cord, a Gore-Tex surgical
      membrane was placed over the cord and fixed to the lateral dural surface with
      stay sutures. During a postoperative follow-up period ranging from 23 months to 7
      years, no further neurological deterioration was observed in the 12 patients and
      magnetic resonance imaging studies showed no adhesion of the spinal cord to the
      operative site. It is concluded that this simple new method is effective for the
      treatment and prevention of tethering and/or retethering of the spinal cord,
      although a longer follow-up study is required.

PMID- 8151349
TI  - Dialysis-associated spondylarthropathy. Report of 10 cases.
AB  - Ten patients undergoing long-term renal dialysis for end-stage renal failure
      developed a destructive, non-infectious spondylarthropathy. All 10 patients had
      biopsy-proven dialysis-associated spondylarthropathy and subsequent spinal
      instability secondary to beta 2-microglobulin deposition in the vertebrae,
      intervertebral disc spaces, and support structures of the spine. Nine patients
      had cervical spinal instability and one had thoracolumbar spinal instability,
      with resultant neural compression. In at least one patient, the spinal
      instability was rapidly progressive. All had received renal dialysis for 34
      months or longer (mean 109 months, range 34 to 154 months). Each patient required
      spinal stabilization (external in seven patients, internal in three). Nine of the
      10 patients underwent neural decompression and spinal stabilization and fusion
      procedures. One patient's neurological condition was worse following surgery due
      to a postoperative cervical epidural hematoma; in the other nine patients, the
      presenting symptoms and signs improved. Three of these chronically ill patients
      did not survive their hospitalization, for a perioperative mortality rate of 30%.
      Death was due to cardiopulmonary arrest in two patients on Day 5 and 9
      postoperatively and to sepsis in the third on Day 14. Of the seven early
      survivors, two additional patients died: one on Day 59 due to congestive heart
      failure and the other on Day 273 due to a cerebrovascular accident. Four of five
      patients who were followed for 8 months or longer (mean 14 months, range 8 to 20
      months) had successful neural decompression and spinal stabilization procedures
      with evidence of stable bone fusion, indicating that these chronically ill,
      difficult-to-manage patients can be successfully treated. Clinicians who treat
      patients with renal disease and neurosurgeons who treat spinal disorders should
      be aware of dialysis-associated spondylarthropathy as a potential cause of
      degenerative vertebral column instability.

PMID- 8151350
TI  - Distinctive electrophysiological characteristics of functionally discrete brain
      areas: a tenable approach to functional localization.
AB  - The direct cortical response (DCR), an electrical potential recorded in the
      immediate vicinity of a surface cortical stimulus, shows a configuration in the
      primary sensory areas of animals that is different from the one observed in
      association cortex. This suggested the possibility that systematic study of the
      DCR in the human brain might reveal a profile of configurations in which the form
      of the response provides functional information about the gyri being tested.
      Studies were carried out in subhuman primates and in patients undergoing surgery
      for tumors, occult vascular malformations, and epilepsy. In the animals, DCR's
      from somatosensory, motor, and association cortex are distinguishable; however,
      there are no differences in configuration between motor and premotor responses,
      or between association responses from prefrontal and parietal cortex. In patients
      with epilepsy due to nonspace-occupying pathology, the responses did not show
      distinguishing features. In contrast, in the patients with tumors or occult
      vascular malformations, DCR's from somatosensory, motor, and premotor cortex
      could be readily distinguished from each other. Responses along the mid and
      posterior sylvian fissure of the dominant hemisphere also had distinctive
      features, but more data are needed before the significance of this finding with
      respect to language function can be assessed. The accumulating results suggest
      that analysis of DCR's may prove to be a useful method for functional
      localization in individuals with focal space-taking pathology.

PMID- 8151351
TI  - Hemodynamics of subarachnoid hemorrhage arrest.
AB  - Subarachnoid hemorrhage (SAH) causes a spectrum of clinical syndromes from mild
      discomfort to rapid brain death. The reason for these heterogeneous consequences
      is poorly understood. A canine autologous shunt model of SAH was used to study
      this problem. The duration and volume of hemorrhage into the suprasellar cistern
      at each animal's mean arterial blood pressure were measured at variable
      hemorrhage flow rates. At high rates of bleeding in seven dogs (18.7 +/- 2.2
      ml/min, mean +/- standard deviation), hemorrhage duration was significantly less
      (191 +/- 116 seconds, p < 0.03) and hemorrhage volume was significantly greater
      (15.1 +/- 7.0 ml, p < 0.05) than at low flow rates. At low flow rates of bleeding
      in nine dogs (4.4 +/- 2.2 ml/min), hemorrhage duration was 394 +/- 202 seconds
      and volume was 10.9 +/- 6.5 ml. Cerebral perfusion pressure (CPP) decreased at
      all hemorrhage rates but never to 0 mm Hg (perfusion arrest). No correlation
      between a decrease in CPP and SAH volume or duration was identified. The initial
      flow rate of SAH had a positive linear correlation with the volume of hemorrhage
      (23 dogs, r = 0.64, p < 0.01). The data suggest that initial SAH flow rate, and
      not CPP, has a primary influence on hemorrhage arrest. This finding may influence
      the clinical rationale for acute management of SAH-induced brain injury.

PMID- 8151352
TI  - Stenosis of central canal of spinal cord in man: incidence and pathological
      findings in 232 autopsy cases.
AB  - The central canal of the spinal cord is generally regarded as a vestigial
      structure that is obliterated after birth in 70% to 80% of the general
      population. This report describes the first detailed histological study of the
      human central canal in 232 subjects ranging in age from 6 weeks' gestation to 92
      years. Whole spinal cords were harvested at autopsy and sectioned serially from
      the conus medullaris to the upper medulla. Histological findings and morphometric
      analysis of the cross-sectional luminal area were used to grade stenosis at seven
      levels of the canal. Varying grades of stenosis were present at one or more
      levels in none (0%) of 60 fetuses, one (3%) of 34 infants, three (18%) of 17
      children, 21 (88%) of 24 adolescents and young adults, 67 (96%) of 70 middle-aged
      adults, and all 27 adults aged 65 years or older (100%). The stenotic process was
      most pronounced in the thoracic segments of the canal and involved more levels
      with higher grades of stenosis in older individuals. Histological findings
      consisted of disorganization of the ependymal epithelium, formation of ependymal
      rosettes or microcanals, proliferation of subependymal gliovascular buds, and
      intracanalicular gliosis. These features are consistent with a pathological
      lesion involving ependymal injury and scarring and are less compatible with an
      involutional or degenerative process. Stenosis of the central canal probably
      influences the anatomical features of syringomyelia and may account for
      variations in cavity formation such as the prevalence of holocord syrinxes in
      children, the formation of focal and paracentral syrinxes in adults, and the rare
      incidence of syrinx formation in many older individuals with acquired lesions
      known to produce syringomyelia.

PMID- 8151353
TI  - Expression of a functional endothelin (ETA) receptor in human meningiomas.
AB  - Endothelin (ET) receptor subtypes (ETA and ETB) in human meningiomas were
      characterized using quantitative receptor autoradiography. A single class of high
      affinity 125I-ET-1 binding sites was localized in all meningioma tissue studied
      (dissociation constant: 2.4 +/- 0.3 nM, maximum binding capacity: 319 +/- 66
      fmol/mg (mean +/- standard error of the mean for 13 tumors)). Unlabeled ET-1
      showed a strong affinity for 125I-ET-1 binding to tissue sections of the tumors
      with a 50% inhibiting concentration (IC50) of 2.9 +/- 0.7 x 10(-9) M, whereas ET
      3 showed a much lower affinity (IC50: 8.4 +/- 2.5 x 10(-6) M). Sarafotoxin S6c, a
      selective agonist for the ETB receptor, could not compete for 125I-ET-1 binding
      to meningiomas. Endothelin-1 significantly stimulated deoxyribonucleic acid (DNA)
      synthesis in a dose-dependent manner in cultured human meningioma cells. In
      contrast, no significant stimulation of DNA synthesis occurred with an S6c
      concentration up to 10(-7) M. Pretreatment of the meningioma cells with pertussis
      toxin, a bacterial toxin that adds adenosine 5'-diphosphate-ribose to the alpha
      subunit of guanine nucleotide binding (G) proteins such as Gi or G(o), induced a
      concentration-dependent reduction in ET-stimulated DNA synthesis in meningioma
      cells, but did not affect the epidermal growth factor-induced DNA synthesis.
      These observations suggest that the ETA receptor is predominantly expressed in
      human meningioma tissue and that ET may act as a growth factor on the meningioma
      cells by interacting with the ETA receptor and by pertussis toxin-sensitive
      mechanisms.

PMID- 8151354
TI  - Meningioangiomatosis of the brain stem. Case report.
AB  - The case is reported of meningioangiomatosis of the brain stem in a 3 1/2-year
      old girl who suffered from vomiting, left facial weakness, difficulty in
      swallowing, and ataxia. This is believed to be the first reported case of
      meningioangiomatosis in the brain stem. Computerized tomography showed an
      intensely enhancing hyperdense mass in the left restiform body. Magnetic
      resonance imaging revealed that the lesion was isointense to gray matter on the
      T1-weighted image and hypointense on the T2-weighted image, with a surrounding
      zone of high T2 signal and intense enhancement. Angiography was normal. Surgical
      exploration demonstrated an intramedullary firm mass that was partially resected.
      Histologically, the mass consisted of a low-grade lesion of meningeal origin with
      spindle cells in a whorling pattern that were occasionally focused around small
      vessels. On 2-year follow-up imaging, the lesion remains unchanged in size.
      Certain particularities of this lesion are discussed in the context of the
      literature.

PMID- 8151355
TI  - Surgical treatment of spontaneous intracranial hypotension associated with a
      spinal arachnoid diverticulum. Case report.
AB  - The authors present the case of a 22-year-old woman who developed spontaneous
      intracranial hypotension as a result of a cerebrospinal fluid leak from a
      thoracic extradural arachnoid diverticulum. The patient was successfully treated
      by ligation of the diverticulum. The entity of spontaneous intracranial
      hypotension and its relevance to neurosurgery are discussed.

PMID- 8151356
TI  - Erythropoietin-augmented isovolemic hemodilution in skull-base surgery. Case
      report.
AB  - Human erythropoietin in concert with intraoperative hemodilution, tumor
      embolization, and surgical staging was used to manage a red blood cell mass in an
      anemic Jehovah's Witness patient with a hypervascular meningioma. Erythropoietin
      (3000 U thrice weekly) and oral iron (1300 mg daily) were given for 1 month prior
      to surgery, raising the hemoglobin level from 11.8 to 14.1 gm/100 ml. A posterior
      fossa craniectomy combined with a temporal craniectomy was then performed so that
      partial petrosectomy, section of the transverse sinus, incision of the tentorium,
      and exposure of the lesion could be carried out. The first stage of the surgery
      was terminated immediately prior to tumor mobilization. Isovolemic hemodilution
      was initiated just before the skin incision. Postoperatively, the hemoglobin
      concentration dropped to 11.5 gm/100 ml. The erythropoietin dose was doubled and
      administration of oral iron continued, leading to a hemoglobin level of 14.0
      gm/100 ml at 1 month after the first operation. The tumor was embolized using
      superselective catheterization. The next day, at the second stage of the surgery,
      the tumor was extirpated, again employing isovolemic hemodilution. By the 4th
      postoperative day, the hemoglobin level had dropped to 9.4 gm/100 ml. The patient
      made an uncomplicated recovery. Erythropoietin therapy contributed substantially
      to the successful outcome of this case. Since erythropoietin has the potential to
      augment all other forms of autologous banking, its role in elective neurosurgery
      may become increasingly important in an era of heightened concern about
      heterologous transfusion.

PMID- 8151357
TI  - Malformation of a cervical facet joint with inclusion of an arthrolith. Case
      report.
AB  - The authors present the case of a 49-year-old man with an isolated malformation
      of the left cervical facet joint at C5-6, with secondary spondylarthrotic
      hypertrophy of the joint leading to involvement of the C-6 nerve root. The
      etiology of this cervical joint malformation is discussed.

PMID- 8151358
TI  - A simple method to ensure proper screw position and plate size selection using
      the Morscher cervical spine locking plate. Technical note.
AB  - The use of bone plate instrumentation with screw fixation has proved to be a
      useful adjunctive measure in anterior cervical spine fusion surgery. Proper
      fitting, positioning, and attachment of this instrumentation have been shown to
      be frequently suboptimal if done without radiographic guidance. The most commonly
      used method of radiographic assistance for placement of this instrumentation is
      fluoroscopy. While this gives satisfactory technical results, it is expensive and
      time-consuming, and exposes the patient and the operating room personnel to
      ionizing radiation. The authors present a simple technique to ensure screw
      placement and plate fitting using Kirschner wires and a single lateral
      radiograph. This technique saves time, reduces exposure to radiation, and has led
      to satisfactory results in over 20 operative cases.

PMID- 8151359
TI  - Accurate placement of coronal ventricular catheter using stereotactic coordinate
      guided free-hand passage. Technical note.
AB  - Long-term patency of the ventricular catheter of a cerebrospinal fluid shunt
      depends on the positioning of the hole-bearing segment of the catheter. Placement
      of this segment near the choroid plexus or injured ependyma increases the
      probability of obstruction. Proper positioning for a coronal shunt in turn
      depends on the ventricular catheter length and target coordinates. The authors
      describe a method of calculating the catheter length based on bone landmarks on
      skull radiographs, and a technique for accurate ventricular catheter placement
      using free-hand passage guided by simple stereotactic coordinates based on
      visible and palpable surface anatomy. The insertion trajectory is aligned with
      the coronal obliquity of the lateral ventricle so that, even with slit
      ventricles, the entire hole-bearing segment of the catheter can be reliably
      situated within the anterior horn. The predetermined catheter length also fixes
      the tip at the foramen of Monro, away from the choroid plexus and injured
      ependyma. Of 160 children undergoing ventriculoperitoneal shunt insertion using
      this technique, only three required catheter revision during a mean follow-up
      period of 39 months. Radiographic grading of the ventricular catheter position in
      112 children showed a satisfactory placement rate of 93.2%; all three children
      with occlusion showed poor catheter positioning. Thus, this method results in
      accurate ventricular catheter placement with a 1.9% obstruction rate, which
      compares favorably to the 16% to 18% incidence of proximal obstruction reported
      in the literature. This technique is applicable to patients of all ages but is
      particularly suitable for children because of the greater variability in head
      size.

PMID- 8151360
TI  - Intraoperative transdural functional mapping. Technical note.
AB  - During craniotomy for supratentorial intraparenchymal space-occupying lesions,
      with the patient either under general anesthesia or awake, a smaller durotomy
      designed to expose only the region of resection may be desirable because of brain
      swelling. Similarly, during repeat craniotomy or craniotomy following cerebral
      injury or infection, pial-dural adhesions increase the risk of damage to
      essential cortex, making a limited dural opening desirable. Intraoperative
      transdural somatosensory evoked potentials and transdural cortical stimulation
      mapping permit localization of functional cortex prior to durotomy. These
      techniques can be combined with intraoperative transdural ultrasonography to
      identify topographical landmarks and borders of mass lesions.

PMID- 8151361
TI  - Stereotactic transtentorial hiatus ventriculoperitoneal shunting for the
      sequestered fourth ventricle. Technical note.
AB  - The authors describe a technique of stereotactic transtentorial hiatus
      ventriculoperitoneal shunting for the treatment of the sequestered fourth
      ventricle, used successfully in the care of four patients. They recommend it as a
      safe, effective treatment of patients suffering from an isolated fourth
      ventricle.

PMID- 8151362
TI  - Evolution of the Journal of Neurosurgery.
AB  - The Journal of Neurosurgery, begun in 1944, has successfully fulfilled the
      purposes of its founders. During the 50 years of its existence it has remained
      pre-eminent in its field, while evolving in presentation, size, and content in
      response to the needs of succeeding generations of neurosurgeons and allied
      specialists. This article draws from the memories of many people, from the
      minutes of meetings of the Editorial Board, and from reports of successive
      editors, and touches on some of the knotty problems faced by those dedicated
      individuals.

PMID- 8151363
TI  - Dorsal rhizotomy: to monitor or not to monitor?

PMID- 8151364
TI  - Natural history of unruptured aneurysms.

PMID- 8151365
TI  - Photodynamic therapy.

PMID- 8151366
TI  - Head injury and therapeutic hypothermia.

PMID- 8151367
TI  - Biopsy of low-grade astrocytomas.

PMID- 8151368
TI  - Health care reform, restructuring predominate at mid-winter meeting.

PMID- 8151369
TI  - An update on radiopharmaceuticals for myocardial perfusion imaging.

PMID- 8151370
TI  - New instrumentation for cardiovascular nuclear medicine.

PMID- 8151371
TI  - Biokinetics of thallium-201 in normal subjects: comparison between adenosine,
      dipyridamole, dobutamine and exercise.
AB  - There are currently four common types of stress used with thallium-201 imaging in
      the diagnosis of coronary artery disease and risk assessment. The objective of
      this study was to examine the thallium biokinetics during exercise, adenosine,
      dipyridamole and dobutamine stress testing in 15 healthy volunteers. METHODS:
      Each subject underwent planar 201Tl imaging during maximal treadmill exercise
      testing, adenosine infusion (140 micrograms/kg/min for 6 min), dipyridamole
      infusion (142 micrograms/kg/min for 4 min) and dobutamine infusion (40
      micrograms/kg/min). RESULTS: Absolute myocardial thallium activity was greater
      after pharmacologic testing than exercise, (p < 0.001 each). Thus, the activity
      was 505 counts/pixel with adenosine, 491 counts/pixel with dipyridamole, 517
      counts/pixel with dobutamine and 409 counts/pixel with exercise. The myocardial
      thallium clearance was lower with pharmacologic testing than exercise; 9.7%/hr
      with adenosine, 9.9%/hr with dipyridamole, 11.3%/hr with dobutamine and 13%/hr
      with exercise (p < 0.01 each). The thallium uptake and clearance in the lung and
      liver were also greater with pharmacologic stress testing than exercise (p <
      0.05). CONCLUSIONS: Thus, thallium biokinetics are different during pharmacologic
      stress testing with adenosine, dipyridamole and dobutamine than during exercise.
      Diagnostic criteria for quantitative analysis of myocardial perfusion imaging
      must therefore be specific for the type of stress used.

PMID- 8151372
TI  - Comparative feasibility of separate or simultaneous rest thallium-201/stress
      technetium-99m-sestamibi dual-isotope myocardial perfusion SPECT.
AB  - Separate or simultaneous rest 201Tl/stress 99mTc-sestamibi dual-isotope SPECT are
      potentially efficient myocardial perfusion imaging protocols which combine the
      use of a high-resolution 99mTc tracer for stress perfusion assessment and 201Tl,
      the current single-photon agent of choice, for viability assessment. METHODS: To
      investigate the feasibility of dual-isotope myocardial perfusion SPECT protocols
      using rest 201Tl and stress sestamibi, 201Tl crosstalk into the 99mTc acquisition
      window (Group 1, n = 26 patients) and 99mTc crosstalk into 201Tl windows (Group
      2, n = 25) were studied. For Group 1, treadmill exercise with sestamibi injection
      and poststress SPECT ("virgin" sestamibi images) were performed, followed by rest
      201Tl injection and SPECT acquisition using dual-isotope windows (contaminated or
      "dual" images). For Group 2, the order was reversed: rest 201Tl SPECT (virgin
      201Tl images) was performed first, followed by exercise sestamibi injection and
      dual-isotope SPECT. RESULTS: The contribution of 201Tl scatter to the dual
      sestamibi images (Group 1) was measured to be 2.9% +/- 2.1%, while 99mTc
      crosstalk contributed 26.7% +/- 13.0% to the dual 201Tl images (Group 2). Image
      quality was considered good to excellent in 92% of the sestamibi (virgin and
      dual) images and 88% of the virgin 201Tl SPECT, but only in 23% of the dual 201Tl
      studies. CONCLUSIONS: Technetium-99m crosstalk into 201Tl windows is substantial;
      therefore, simultaneous dual-isotope protocols, which involve assessment of 201Tl
      images contaminated by 99mTc, are not recommended. On the other hand, because of
      the small amount of 201Tl crosstalk into the 99mTc window, a separate acquisition
      dual-isotope approach employing the rest 201Tl (virgin)/stress sestamibi sequence
      is acceptable.

PMID- 8151373
TI  - Sequential dual-isotope SPECT imaging with thallium-201 and technetium-99m
      sestamibi.
AB  - This study examined the results of sequential SPECT dual-isotope imaging with
      201Tl and 99mTc-sestamibi in 148 patients, 114 of whom also had coronary
      angiography and 34 had < 5% pretest probability for coronary artery disease
      (CAD). METHODS: Stress thallium/rest sestamibi was used in 82 patients and rest
      thallium/stress sestamibi in 66 patients. Coronary angiography showed that 17
      patients had no CAD, 27 patients had one-vessel CAD, 41 patients had two-vessel
      CAD and 29 patients had three-vessel CAD. The thallium study (3 mCi) was always
      done before the sestamibi study (20-25 mCi). The stress was either symptom
      limited treadmill exercise testing or adenosine infusion at a rate of 140
      micrograms/kg/min for 6 min. RESULTS: The study was completed within 2 hr. The
      stress and rest images were normal in 11 of 17 patients (65%) with no CAD by
      angiography and in 33 of 34 patients with a low pretest probability of CAD
      (normalcy rate = 97%). The images were abnormal in 75 patients with CAD (77%).
      The perfusion pattern was compared to wall motion in 485 segments (97 patients)
      assessed by contrast ventriculography. There were no or reversible perfusion
      defects in 357 of 386 segments (92%) with no wall motion abnormality. CONCLUSION:
      Sequential dual-isotope imaging is feasible and can be completed in a short
      period of time and may therefore enhance laboratory throughput and patient
      convenience.

PMID- 8151374
TI  - Prognostic value of normal technetium-99m-sestamibi cardiac imaging.
AB  - The purpose of this study was to describe the clinical outcome of patients with a
      normal 99mTc-sestamibi cardiac imaging study. METHODS: One-day gated rest-stress
      planar dipyridamole (n = 112) and symptom-limited exercise (n = 122) 99mTc
      sestamibi protocols were used. All patients (n = 234, mean age 55 +/- 12 yr, 127
      males and 107 females) had normal perfusion and wall motion on qualitative
      analysis. Patients were followed for 6-16 mo (mean 10 +/- 2 mo). Cardiac events
      were defined as cardiac death or nonfatal myocardial infarction. RESULTS: ST
      segment depression or chest pain occurred in 8 (7%) and 29 (26%) patients in the
      dipyridamole group, respectively, and 20 (16%) and 28 (22%) patients in the
      exercise group. Cardiac events occurred in only one patient. The annualized event
      rate was 0.5% per year. In addition, only two patients underwent coronary
      revascularization during the follow-up period. CONCLUSIONS: Our data confirm the
      benign outcome of patients with normal 99mTc-sestamibi cardiac imaging, at least
      over an intermediate follow-up period.

PMID- 8151375
TI  - Effects of time discrepancies between input and myocardial time-activity curves
      on estimates of regional myocardial perfusion with PET.
AB  - Estimates of myocardial perfusion with PET using kinetic models require faithful
      recording of radioactivity content in blood and myocardium. Typically the
      arterial time-activity curve is obtained by placing a region of interest (ROIs)
      within the left atrial or left ventricular cavity. However, curves generated from
      these regions appear earlier in time than tissue time-activity curves obtained
      from ROIs within the myocardial tissue, and such time discrepancies can lead to
      errors in flow estimates. METHODS: The magnitude of these time discrepancies and
      their effect on estimates of regional myocardial perfusion using oxygen-15-water
      were measured in 30 normal subjects evaluated at rest and again after
      administration of dipyridamole. RESULTS: Under baseline conditions, the left
      atrial curve appeared 0.97 +/- 0.67 (s.d.) before the ascending aorta input curve
      (p < 0.05) and estimated perfusion decreased from 1.28 +/- 0.28 ml/g/min using
      the left atrial curve uncorrected for time to 0.98 +/- 0.27 ml/g/min after
      correction (p < 0.05). After dipyridamole, the left atrial curve appeared 0.68 +/
      0.72 sec before the ascending aorta curve (p < 0.05) and estimated perfusion
      decreased from 3.60 +/- 1.40 ml/g/min using the left atrial curve uncorrected for
      time to 3.24 +/- 1.26 ml/g/min using the time-corrected curve (p < 0.05). Because
      the magnitude of time discrepancies between the left ventricular and ascending
      aortic curves was less (0.25 +/- 0.34 and 0.19 +/- 0.23 sec at rest and after
      dipyridamole, respectively), effects on flow estimates were more modest.
      CONCLUSIONS: The results of this study demonstrate that time discrepancies
      between input and tissue time-activity curves can affect estimates of myocardial
      flow. Correction for this potential source of error is proposed.

PMID- 8151376
TI  - Whither water?

PMID- 8151377
TI  - Significance of defect severity in technetium-99m-MIBI SPECT at rest to assess
      myocardial viability: comparison with fluorine-18-FDG PET.
AB  - The pathophysiological significance of 99mTc-MIBI uptake at rest for assessing
      myocardial viability in patients with coronary artery disease (CAD) is still
      controversial. Therefore, we studied the relationship of 99mTc-MIBI uptake at
      rest and preserved or absent uptake of 18FDG as assessed with PET in 111
      consecutive patients after overnight withdrawal of their antianginal medication.
      METHODS: Each ventricle was evaluated in 13 segments derived from 25 regions of
      interest (ROIs) in short-axis cuts and 18FDG uptake was normalized to the
      intraindividual normal reference ROI (ROI with maximal = 100% 99mTc-MIBI uptake).
      Segments with a normalized 18FDG uptake > 70% were defined as viable while
      segments with a 18FDG uptake < 50% were defined as nonviable. RESULTS: Five to
      11% of segments with 99mTc-MIBI uptake at rest < or = 30% of peak activity were
      viable and 80%-84% nonviable. Of moderate to severe 99mTc-MIBI defects at rest
      (31%-70% of peak), 13%-61% were viable. Segmental 99mTc-MIBI uptake and
      normalized 18FDG uptake were linearly correlated (r = 0.61, n = 1443, p < 0.001).
      In segments revealing severely reduced 99mTc-MIBI uptake (< or = 50% of peak) the
      correlation was considerably lower (r = 0.44, n = 295, p < 0.001). CONCLUSIONS:
      In patients with CAD, 99mTc-MIBI uptake underestimates myocardial viability in
      comparison to 18FDG-PET. Myocardial 99mTc-MIBI uptake therefore appears to
      reflect myocardial blood flow rather than myocardial viability. Patients with
      moderate and severe 99mTc-MIBI defects at rest may benefit from additional
      metabolic PET imaging prior to final therapeutic decisions.

PMID- 8151378
TI  - Clinical utility of technetium-99m-teboroxime myocardial washout imaging.
AB  - The purpose of this study was to evaluate the clinical utility of 99mTc
      teboroxime myocardial washout imaging. The differential washout after a single
      tracer injection has been proposed as an alternative for characterization of the
      perfusion defects. METHODS: Fifty-six patients received 5-min adenosine infusion.
      The stress dose of 99mTc-teboroxime was injected at 4.5 min and stress imaging
      with a single-headed SPECT gamma camera was started at 6 min, washout imaging
      followed immediately. At 20 min, the rest tracer dose was injected at rest and
      imaging was started at 21.5 min. The reversibility of the perfusion defects on
      the washout and rest images was compared visually and quantitatively. RESULTS:
      There was no statistical difference in the number of stress defects that improved
      on the washout and rest images. The visual interpretation of the perfusion
      abnormalities was confirmed by quantitative analysis of relative segmental
      activity. CONCLUSION: Thus, 99mTc-teboroxime-adenosine washout myocardial
      perfusion imaging can be safely and quickly accomplished. Detected reversibility
      of the perfusion defects did not significantly differ from reversibility observed
      on the rest images.

PMID- 8151379
TI  - Comparison of technetium-99m-Q3 and thallium-201 for detection of coronary artery
      disease in humans.
AB  - Technetium-99m-Q3 is a myocardial imaging agent that produces prompt myocardial
      visualization in humans. METHODS: In 19 patients with angiographic coronary
      artery disease, 2 patients with no angiographic coronary artery stenosis greater
      than 50% of the luminal diameter and 6 healthy volunteers, exercise and resting
      myocardial imaging were performed with 99mTc-Q3 and also with 201Tl. Technetium
      99m-Q3 imaging began 15 min after injection at rest and with exercise, in a
      complete imaging sequence that required less than 100 min. RESULTS: Overall
      accuracy for coronary disease detection was 78% (21 true-positive or true
      negative studies among 27 study participants) by tomographic thallium imaging
      versus 89% for 99mTc-Q3 tomographic imaging (p = ns). Accuracy for detection of
      individual coronary stenoses was 75% (61 true-positive or true-negative coronary
      segment classifications among 81 total coronary segments) for 201Tl imaging and
      83% for 99mTc-Q3 imaging (p = ns). CONCLUSIONS: Technetium-99m-Q3 when used in a
      rest-exercise sequence that can be completed in 100 min appears to provide
      comparable diagnostic accuracy to 201Tl for overall coronary disease detection
      and detection of individual coronary artery stenoses.

PMID- 8151380
TI  - Technetium-99m-tetrofosmin myocardial imaging: a comparison with thallium-201 and
      angiography.
AB  - Images recorded after intravenous administration of 99mTc-tetrofosmin were
      compared to those obtained with 201Tl in a series of 40 patients with
      angiographically documented coronary artery disease. These patients were part of
      a Phase II tetrofosmin study and presented anamnestic or laboratory evidence
      suggestive of ischemic heart disease. METHODS: Thirty-seven patients had one or
      more coronary obstructions greater or equal to 70% of luminal diameter. Three
      patients studied after bypass surgery or angioplasty had patent grafts, absence
      of disease progression or no significant restenosis. Twenty-six patients had
      evidence of previous myocardial infarction. All images were processed into a
      common display format by a core laboratory. They were identified by code and read
      by concensus of four investigators. Each segment was classified as normal or
      abnormal and these readings were combined and categorized into normal,
      reversible, fixed or mixed regional defects. RESULTS: There was good segmental
      correspondence between thallium and tetrofosmin (kappa values ranged from 0.43 to
      1.00). The ability of thallium and tetrofosmin to recognize and localize
      myocardial infarction was excellent, since corresponding abnormalities were
      present in respectively 24 and 25 of the 26 patients with previous myocardial
      infarction. Abnormalities in noninfarcted territories were recognized with both
      tracers in 16 of 28 patients presenting with coronary lesions involving vessels
      unrelated to the infarct. CONCLUSION: In comparison to rest tetrofosmin, thallium
      redistribution shows more reversibility in areas with myocardial infarction but
      less reversibility in areas of myocardial ischemia. Current Phase II results
      suggest that tetrofosmin is a sensitive and reliable tracer for detecting
      myocardial infarction and ischemia. Results should be confirmed in a larger group
      of patients.

PMID- 8151381
TI  - Myocardial tomography using technetium-99m-tetrofosmin to evaluate coronary
      artery disease.
AB  - To assess the clinical value of the 99mTc-labeled myocardial perfusion agent,
      99mTc-tetrofosmin, the findings of stress and rest myocardial tomography were
      compared with those of stress and 3-hr delayed 201Tl tomography and coronary
      arteriography. METHODS: Twenty-five patients who had coronary arteriography were
      studied with both stress tetrofosmin and 201Tl tomography. RESULTS: The image
      quality of tetrofosmin was superior to that of 201Tl despite a shorter
      acquisition time. Both the tetrofosmin and 201Tl studies were quite sensitive to
      detect coronary artery disease (100% and 95%, respectively) (p = ns). The two
      studies showed similar sensitivity (75% and 73%) and specificity (80% and 77%,
      respectively) for the detection of significant (> or = 75% diameter) coronary
      artery stenosis. Stress distribution of tetrofosmin tended to be slightly higher
      than that of 201Tl (% uptake: 63.3% +/- 13.5% versus 60.4% +/- 12.2%, p = 0.0006;
      uptake score: 2.33 +/- 1.03 versus 2.22 +/- 1.07, p = 0.007), indicating less
      defect contrast in the former. A high concordant rate (89%) of the stress
      perfusion score was observed between the two radiopharmaceuticals. Reversible
      perfusion abnormalities were observed to be similar between stress-rest
      tetrofosmin and stress-delayed 201Tl studies. CONCLUSIONS: Stress tetrofosmin
      perfusion tomography is a valuable method to detect coronary artery disease and
      to assess tissue viability with accuracy similar to that of stress 201Tl
      tomography.

PMID- 8151382
TI  - A multicenter trial on interobserver and intraobserver reproducibility of
      segmental scoring of thallium-201 planar myocardial imaging before and after
      reinjection. Italian Group of Nuclear Cardiology.
AB  - Inter- and intraobserver reproducibility (R) of segmental 201Tl scores after
      stress (ST), redistribution (RD) and reinjection (RI) planar imaging were
      evaluated. METHODS: Images were examined from 396 patients with suspected
      coronary artery disease, demonstrated by means of post-ST imaging of at least one
      perfusion defect. To eliminate external sources of variability, the same gamma
      camera, acquisition protocol and computer software were used in this multicenter
      study. Thallium-201 images of the anterior, left anterior oblique and left
      lateral projections were obtained immediately, 4 hr after exercise and 30 min
      after the injection of additional 201Tl either on the same day or on a different
      day. The left ventricle was divided into 15 segments and evaluated by three
      independent observers, blinded to clinical data, according to a five-point scale.
      RESULTS: The R score for ST, RD and RI images, expressed as an intraclass
      correlation coefficient, was 0.76, 0.74 and 0.72, respectively. After averaging
      multiple observer scores, R increased to 0.91, 0.90 and 0.89, respectively.
      Individual observer measurement of the R score was 0.48, 0.51 and 0.32 for ST-RD,
      ST-RI and RD-RI image pairs, respectively, and multiple observer scores showed R
      increases to 0.74, 0.76 and 0.58. CONCLUSION: This qualitative scale reliably
      assesses the severity of 201Tl perfusion defects, particularly when multiple
      observer scores are averaged. Individual observer change scores should be taken
      with great caution, especially in studies involving the visual evaluation of RD
      RI image changes.

PMID- 8151383
TI  - Multicenter trial validation for quantitative analysis of same-day rest-stress
      technetium-99m-sestamibi myocardial tomograms.
AB  - The accuracy of an automated quantitative analysis of same-day rest/stress 99mTc
      sestamibi SPECT images for detection and localization of coronary artery disease
      (CAD) was assessed in a multicenter trial consisting of 161 patients from 7
      different clinical sites utilizing various camera computer systems. METHODS: Of
      the 161 patients, 102 had angiographically documented coronary artery disease, 22
      had normal coronary arteriograms, and 37 had a low (< 5%) likelihood of coronary
      artery disease based on their age, sex, symptoms and the results of their
      exercise electrocardiograms. The patients were studied using previously optimized
      image acquisition and processing protocols. An additional population consisting
      of 45 patients with single-vessel disease were evaluated to determine the optimal
      criteria for detection of CAD. RESULTS: The quantitative analysis method was
      associated with an overall sensitivity of 87%, specificity of 36%, and normalcy
      rate (true negative rate in the low likelihood patients) of 81%. Sensitivity for
      overall detection of disease was similar (90%) in patients with and without
      myocardial infarction (90% versus 89%). The sensitivities and specificities for
      identification of disease in individual coronary arteries were, respectively, 69%
      and 76% for LAD, 70% and 80% for LCX, and 77% and 85% for RCA. CONCLUSION: The
      results of this study demonstrate that the new objective quantitative method for
      analysis of same-day rest/stress 99mTc sestamibi SPECT images is accurate for
      detection and localization of CAD and correlates highly with expert visual
      interpretation.

PMID- 8151384
TI  - Significant gastric reflux of technetium-99m-MIBI in SPECT myocardial imaging.
AB  - We present a case in which significant gastric reflux of 99mTc-methoxy
      isobutylisonitrile (MIBI) was observed in a patient who underwent stress/rest
      99mTc-MIBI SPECT myocardial perfusion imaging for suspected coronary artery
      disease. The intense gastric activity partially obscured myocardial uptake of
      99mTc MIBI, particularly in the inferolateral wall of the left ventricle. The
      presence of significant gastric activity should be considered when performing
      SPECT myocardial imaging with 99mTc MIBI, and, where necessary, steps should be
      taken to minimize this activity prior to commencing acquisition.

PMID- 8151385
TI  - Improved detection of viable myocardium with thallium-201 reinjection in chronic
      coronary artery disease: comparison with technetium-99m-MIBI imaging.
AB  - Exercise-redistribution 201Tl with reinjection at rest and exercise-rest 99mTc
      methoxy isobutyl isonitrile (MIBI) cardiac imaging was performed in a patient
      with multivessel chronic coronary artery disease (CAD) and evaluated before and
      after coronary revascularization. Thallium reinjection showed reversible defects
      of the inferior and septal walls and irreversible defect of the infero-apical
      region. Technetium-99m-MIBI scintigraphy demonstrated irreversible defects of the
      inferior, septal and infero-apical regions. After coronary artery bypass grafts,
      both thallium reinjection and 99mTc-MIBI images showed only irreversible defects
      of the infero-apical region. Functional recovery of the inferior and septal walls
      was observed on two-dimensional echocardiography. Thallium reinjection identifies
      severely ischemic but viable myocardium more accurately than 99mTc-MIBI in
      chronic CAD. Thallium myocardial imaging with reinjection at rest is recommended
      for evaluating patients with chronic ischemic left ventricular dysfunction to
      determine if these patients are candidates for revascularization procedures.

PMID- 8151386
TI  - Extended acquisition for minimizing attenuation artifact in SPECT cardiac
      perfusion imaging.
AB  - Artifacts due to attenuation can complicate the interpretation of SPECT cardiac
      perfusion images, especially when the attenuated region corresponds to that of a
      coronary vascular distribution. Since methods of correction are limited, some
      patients undergo coronary angiography unnecessarily. Acquisition using a three
      detector camera provides more data that can serve to minimize the effects of
      localized attenuation if incorporated into the final reconstruction set. In this
      article, a practical approach for interpreting SPECT cardiac perfusion images is
      outlined, demonstrating with an illustrative case how this approach can be
      clinically helpful.

PMID- 8151387
TI  - Receptor imaging with atrial natriuretic peptide. Part 1: High specific activity
      iodine-123-atrial natriuretic peptide.
AB  - METHODS: Atrial natriuretic peptide (ANP) was labeled in high specific activity
      using 123I (p,2n). The biodistribution of 123I-ANP was studied in green vervet
      monkeys by gamma scintigraphy and in rats by dissection and gamma counting.
      Iodine-125-ANP was also studied in monkeys by in vitro autoradiography. RESULTS:
      Iodine-123-ANP showed rapid blood clearance with localization to ANP receptors in
      the kidneys and lungs, which accounted for 35% of total uptake. In vivo
      competition imaging studies using cold ANP99-126 and C-ANP102-121 proved that
      uptake is receptor mediated and allowed imaging of the differential
      biodistribution of A/B and C-ANP receptor families. Thus, it was possible through
      the use of selective receptor occupation to prevent uptake in certain organs and
      to effectively steer the labeled ANP to others. The observed biodistribution
      patterns were confirmed by an in vitro study using 125I-ANP in the same monkeys,
      which correlated the scintigraphic images with receptor distribution. An in vivo
      biodistribution study in rats showed a profound effect of specific activity on
      biodistribution, with a cutoff for receptor uptake at less than 3000 Ci/mmole.
      CONCLUSION: Gamma scintigraphy with 123I-ANP permits the imaging of ANP receptors
      in vivo. In contrast to receptor imaging with either organic molecules or
      antibodies, ANP provides rapid first-pass uptake and substantial accumulation
      (%dose/organ approximately 20% or greater) in receptors. The key to receptor
      imaging with peptides is high specific activity. Labeled ANP offers potential as
      a diagnostic tool for diabetic nephropathy, particularly for quantifying the
      involvement of glomerular disease.

PMID- 8151388
TI  - Defects on SPECT "perfusion" images can occur due to abnormal segmental
      contraction.
AB  - Technetium-99m-sestamibi images reflect tracer distribution at the time of
      injection. This "stay put" indicator allowed us to separate the effects of
      segmental left ventricular dysfunction per se versus myocardial blood flow on
      SPECT "perfusion" images in ten dogs. METHODS: An electromagnetic flow probe and
      hydraulic occluder were placed on the LAD coronary artery. Sonomicrometry was
      used to measure segmental wall shortening. At peak myocardial blood flow induced
      by adenosine, 35-45 mCi 99mTc-sestamibi were injected without occlusion. At 1 hr
      postinjection, during normal contraction, 40-50 msec end-diastolic and end
      systolic SPECT images (#1) were acquired to reflect normal myocardial blood flow
      distribution. Later, during total LAD occlusion, and without reinjection of
      isotope, another gated scan (#2) was acquired. RESULTS: Coincident with abnormal
      contraction, large severe systolic defects [(28 +/- 5)% more severe compared to
      the baseline-scan #1; p < 0.01], and milder diastolic defects [(12 +/- 8)% more
      severe compared to the baseline-scan #1; p < 0.01] were observed during scan #2.
      Thus, abnormal contraction alone produced defects on SPECT images. CONCLUSION:
      Accordingly, defects in myocardial perfusion images must be interpreted as
      representing the integrated result of the combination of blood flow and segmental
      contraction heterogeneity.

PMID- 8151389
TI  - A count-based radionuclide method for volume quantitation using conjugate imaging
      and an external reference source: theoretical consideration and phantom study.
AB  - A count-based method was developed for ventricular volume determination during
      multigated equilibrium cardiac blood-pool imaging (MUGA). METHODS: Two sets of
      conjugate images of the volume were obtained, one with an external reference
      overlying the volume and the other without. The reference has known activity and
      dimension. The ratio of the geometric mean count rates over a pixel obtained from
      these two conjugate images, Ratio(geo), and the ratio of the specific activity in
      the reference to that in the volume, Ratio(ext), were used to calculate the
      length of the volume over that pixel perpendicular to the camera face, H, as a
      function of the length of the reference source, R, and the attenuation
      coefficient, ub, of the volume: [formula: see text] Based on H, the volume is
      then calculated. This method corrects for attenuation directly and determines the
      volume explicitly. To validate this method, phantom studies are carried out with
      known volumes of 99mTc containing saline solutions in situations of variable
      amount of attenuating medium and background activity. RESULTS: In all cases, the
      calculated volume agrees closely with the actual volume. CONCLUSION: This is an
      accurate method of volume quantitation that is well suited for determining
      ventricular volume during MUGA studies.

PMID- 8151390
TI  - Comparison of americium-241 and technetium-99m as transmission sources for
      attenuation correction of thallium-201 SPECT imaging of the heart.
AB  - This study compares the ability of 241Am and 99mTc to estimate 201Tl attenuation
      maps while minimizing the loss in the precision of the emission data. METHODS: A
      triple-head SPECT system with either an 241Am or 99mTc line source opposite a fan
      beam collimator was used to estimate attenuation maps of the thorax of an
      anthropomorphic phantom. Linear attenuation values at 75 keV for 201Tl were
      obtained by linear extrapolation of the measured values from 241Am and 99mTc.
      RESULTS: Lung and soft-tissue estimates from both isotopes showed excellent
      agreement to within 3% of the measured values for 201Tl. Linear extrapolation did
      not yield satisfactory estimates for bone from either 241Am (+11.7%) or 99mTc (
      15.3%). Patient data were used to estimate the dependence of crosstalk on patient
      size. Contamination from 201Tl in the transmission window was 5-6 times greater
      for 241Am compared to 99mTc, while the contamination in the 201Tl data in the
      transmission-emission detector head (head 1) was 4-5 times greater for 99mTc
      compared to 241Am. No contamination was detected in the 201Tl emission data of
      heads 2 and 3 from 241Am, whereas the 99mTc produced a small crosstalk component
      giving a signal-to-crosstalk ratio near 20:1. Measurements with a fillable chest
      phantom estimated the mean error introduced into the data from the removal of the
      crosstalk. CONCLUSION: Based on the measured data, 241Am is a suitable
      transmission source for simultaneous transmission-emission tomography for 201Tl
      cardiac studies.

PMID- 8151391
TI  - Technetium-99m-tetrofosmin to assess myocardial blood flow: experimental
      validation in an intact canine model of ischemia.
AB  - Technetium-99m-tetrofosmin is a 99mTc-labeled perfusion tracer demonstrating
      promise for myocardial perfusion imaging. To determine if 99mTc-tetrofosmin
      tracks myocardial flow over a pathophysiologic range, the initial myocardial
      uptake and clearance of 99mTc-tetrofosmin relative to microsphere flow were
      evaluated in a canine model of ischemia during pharmacological vasodilatation.
      METHODS: Six open-chest dogs were subjected to complete left anterior descending
      coronary artery occlusion. Dogs were injected with 99mTc-tetrofosmin and
      radiolabeled microspheres during pharmacological stress. Coincident with
      radiotracer injection, dynamic planar imaging and arterial sampling were
      performed to assess 99mTc-tetrofosmin clearance from blood, myocardium, lung and
      liver. Fifteen minutes after injection, hearts were excised for well counting of
      myocardial 99mTc-tetrofosmin activity and flow. RESULTS: Myocardial 99mTc
      tetrofosmin activity correlated linearly with microsphere flow (r = 0.84).
      Relative 99mTc-tetrofosmin activity underestimated flow at higher flow ranges (>
      2.0 ml/min/g) and overestimated flow in low flow ranges (< 0.2 ml/min/g).
      Technetium-99m-tetrofosmin cleared rapidly from the blood and was retained in the
      myocardium. Resting target-to-background activity ratios (heart:lung = 3.57 +/-
      1.01; heart:liver = 0.58 +/- 0.04) were acceptable 10 min after injection.
      CONCLUSION: Our experimental data support both the validity of 99mTc-tetrofosmin
      as a myocardial perfusion tracer and the use of early poststress 99mTc
      tetrofosmin imaging for the assessment of myocardial perfusion in man.

PMID- 8151392
TI  - Cardiovascular nuclear medicine: state-of-the-art.

PMID- 8151393
TI  - Myocardial perfusion imaging with thallium-201.
AB  - Over the past 15 yr, numerous clinical studies have validated the use of
      myocardial perfusion imaging with 201Tl for detection and evaluation of coronary
      artery disease (CAD). In addition, 201Tl scintigraphy plays a valuable role in
      the risk stratification of patients with suspected or known CAD to determine
      prognosis. Typical protocols involve a comparison of stress and rest images to
      locate regions of myocardial ischemia. Results are comparable from protocols that
      employ either exercise stress or pharmacologic stress. By combining 201Tl
      scintigraphic criteria with electrocardiographic (ECG) data, the sensitivity for
      detection of ischemia may be increased by as much as 25%-30%. The introduction of
      quantitative interpretation and SPECT has increased the accuracy of myocardial
      perfusion imaging with 201Tl. With respect to prognosis, several 201Tl scan
      variables, such as multiple perfusion defects and abnormal 201Tl lung uptake, are
      associated with high risk. Even when cardiac catheterization findings are known,
      201Tl scintigraphy provides important supplementary information for identifying
      high-risk subgroups of patients with CAD.

PMID- 8151394
TI  - Myocardial perfusion imaging with technetium-99m-sestamibi: comparative analysis
      of available imaging protocols.
AB  - Several protocols for rest and stress myocardial perfusion imaging with 99mTc
      sestamibi have been developed, each with distinct advantages and disadvantages.
      The various approaches have similar sensitivities and specificities for detection
      of coronary artery disease (CAD), but differ mainly in their ability to identify
      defect reversibility. The dual-isotope approach, with a rest 201Tl study and a
      stress 99mTc-sestamibi study, permits optimal evaluation of both stress perfusion
      and defect reversibility. Gated SPECT may be added to any of the protocols and
      aids in identifying artifacts, defining regional wall thickening and assessing
      ventricular function. First-pass 99mTc-sestamibi radionuclide angiography can add
      exercise ventricular function data to the study. Clinical trials have shown that
      the various protocols for 99mTc-sestamibi provide diagnostic and prognostic
      information comparable to that derived from traditional 201Tl imaging, with the
      added advantage of higher quality images and increased certainty in
      interpretation.

PMID- 8151395
TI  - Myocardial perfusion imaging with technetium-99m-teboroxime.
AB  - Technetium-99m-teboroxime is a myocardial perfusion imaging radiotracer that,
      although not widely used in clinical practice, has the potential to provide
      valuable diagnostic information. Teboroxime's high myocardial extraction and
      rapid in vivo myocardial clearance make stress/rest studies possible using very
      short imaging protocols. In addition, differential washout of 99mTc-teboroxime
      produces defect filling on early delayed images in a high percentage of patients,
      potentially eliminating the need for a second rest injection. Finally, because of
      its rapid myocardial clearance, serial injections of 99mTc-teboroxime in an acute
      myocardial infarction (MI) setting can provide information on infarct vessel
      patency based on defect size and can help document the success or failure of
      reperfusion therapy.

PMID- 8151396
TI  - Myocardial perfusion imaging with PET.
AB  - Although SPECT has become an accepted imaging technique for myocardial perfusion
      studies, there are several advantages to evaluating coronary artery disease (CAD)
      with PET. CAD is a complex, dynamic disease and quantitative measurements of
      myocardial blood flow by PET can improve the functional characterization of CAD.
      The major advantage of PET over SPECT is its ability to provide attenuation
      corrected images, which decreases incidence of attenuation artifacts and
      increases specificity. Myocardial perfusion imaging with PET can also provide
      more accurate information on localization of disease, as well as quantitative
      assessment, in absolute values, of myocardial blood flow. The measurement of
      regional flow reserve allows for physiologic characterization of stenosis
      severity, and may provide early detection of CAD as well as prognostic
      information. The disadvantage of PET, compared to SPECT, is that the equipment
      and operations are more expensive. As more accurate diagnostic and prognostic
      data lead to improved patient management, the cost-to-benefit ratios of PET and
      SPECT in the clinical setting need to be further analyzed to determine which
      diagnostic test is most efficient in the work-up of patients with suspected or
      known CAD.

PMID- 8151397
TI  - How to detect and avoid myocardial perfusion SPECT artifacts.
AB  - Although myocardial perfusion imaging with SPECT is an accurate and reliable
      diagnostic study, artifacts must be avoided, or detected and corrected, to
      minimize the rate of false-positive results. Common sources of artifacts are
      nonuniformity in gamma camera detectors, center of rotation errors, misaligned
      cameras on multidetector scanner systems, errors in image reconstruction, patient
      motion, radiotracer uptake in nontarget organs and attenuation. Some of these
      artifacts can be avoided by quality control of instrumentation and by imaging the
      patient in a prone rather than supine position to separate radiotracer activity
      from the target and nontarget organs and to reduce the effect of inferior wall
      attenuation. Other artifacts can be detected by careful image inspection and
      corrected by reprocessing. The best way to avoid artifacts is to pay very close
      attention to the technical factors of image acquisition and processing, and to be
      aware of attenuation factors.

PMID- 8151398
TI  - The role of stress redistribution thallium-201 myocardial perfusion imaging in
      evaluating coronary artery disease and perioperative risk.
AB  - Thallium-201 myocardial perfusion imaging can provide prognostic information on
      the risk of future cardiac events in patients with known or suspected chronic
      coronary artery disease (CAD). In addition, patients at risk for cardiac events
      during surgery can be risk-stratified preoperatively with myocardial perfusion
      studies. The presence or absence of transient defects on perfusion images is a
      strong predictor of subsequent cardiac events. The extent of transient defects,
      which reflects the extent of jeopardized yet viable myocardium, is useful to
      predict patient outcome. Myocardial perfusion imaging with 201Tl adds significant
      prognostic value to standard ECG and clinical data.

PMID- 8151399
TI  - Role of thallium-201 and PET imaging in evaluation of myocardial viability and
      management of patients with coronary artery disease and left ventricular
      dysfunction.
AB  - The reported mortality of patients with coronary artery disease (CAD) and
      congestive heart failure is high but variable. In the clinical management of
      these patients, the available treatment choices are medical therapy, cardiac
      transplantation and myocardial revascularization. Myocardial revascularization
      has become an attractive alternative in the management of patients with CAD and
      poor left ventricular function because medical therapy is associated with a high
      mortality and cardiac transplantation is expensive and not practical due to
      shortage of donor hearts. Myocardial revascularization, however, should be
      recommended in those patients in whom the procedure is very likely to reverse
      regional and global left ventricular dysfunction and to improve heart failure
      symptoms and survival. Thallium-201 rest-redistribution myocardial scintigraphy
      and PET imaging of myocardial perfusion and 18F-fluoro-deoxyglucose metabolism
      have been extensively evaluated for the assessment of myocardial viability and
      for prediction of recovery of regional left ventricular dysfunction following
      myocardial revascularization; with positive and negative predictive accuracies of
      72% and 70% for 201Tl rest-redistribution imaging and 83% and 84% for perfusion
      metabolism PET imaging. Both modalities also are predictive of improvement in
      left ventricular ejection fraction after myocardial revascularization. Patients
      with congestive heart failure who demonstrate the PET pattern of mismatch are
      more likely to improve their heart failure symptoms following revascularization
      than those without the mismatch pattern. Furthermore, the PET pattern of mismatch
      identifies a subgroup of patients who are at very high risk for cardiac death on
      medical therapy. Survival of these patients can be significantly improved by
      myocardial revascularization.

PMID- 8151400
TI  - Exercise and pharmacologic stress testing for prognosis after acute myocardial
      infarction.
AB  - To evaluate patients after acute myocardial infarction (MI), myocardial perfusion
      imaging provides prognostic parameters that help identify patients at risk for
      subsequent cardiac events. In addition, myocardial perfusion imaging can be used
      to identify functionally important residual stenoses and multivessel disease,
      even in patients who have received thrombolytic therapy. Three parameters of
      myocardial perfusion imaging emerge as strong predictors of future cardiac events
      in post-MI patients: (1) presence of transient defects, (2) the number of
      transient defects and (3) increased radiotracer uptake in the lung. In addition,
      radionuclide left ventricular ejection fraction (LVEF) is one of the most
      powerful predictors of subsequent risk for cardiac events, particularly cardiac
      death and congestive heart failure. Cardiac catheterization, for the most part,
      does not add to the prognostic value of radionuclide stress testing. Results of
      myocardial perfusion imaging studies that employ pharmacologic stress instead of
      submaximal exercise provide strong predictors of prognosis in post-MI patients.

PMID- 8151401
TI  - The role of radionuclide ventriculography in the assessment of prognosis in
      patients with CAD.
AB  - One of the most important roles of cardiovascular nuclear medicine in evaluating
      patients with coronary artery disease (CAD) is predicting patient outcome.
      Measurements of ventricular function obtained by radionuclide ventriculography
      play a key role in defining a patient's prognosis. Because ventricular function
      correlates well with the total extent of myocardial ischemic burden, data derived
      from radionuclide ventriculography serve as valuable prognostic indicators.
      Radionuclide ventriculography provides noninvasive information that is comparable
      to contrast angiography for predicting subsequent cardiac events and mortality in
      patients with CAD.

PMID- 8151402
TI  - Exercise myocardial perfusion imaging.
AB  - The role of physical exercise in myocardial perfusion imaging is critical for two
      reasons: (1) stress is essential to create heterogeneity of blood flow in
      myocardial regions supplied by normal versus stenosed coronary arteries and (2)
      exercise data provide invaluable information that can influence the
      interpretation of perfusion images. Image interpretation and correlation with
      exercise data provide important prognostic information on a patient's risk for
      subsequent cardiac events.

PMID- 8151403
TI  - Dipyridamole myocardial perfusion imaging.
AB  - Dipyridamole is a pharmacologic stressor used in place of exercise for myocardial
      perfusion imaging in patients who cannot exercise due to various physical
      limitations. Perfusion studies with dipyridamole can identify coronary artery
      disease (CAD) as accurately as maximal exercise stress testing. In addition,
      dipyridamole myocardial perfusion studies are useful to stratify patients
      according to risk of subsequent cardiac events. As dipyridamole is infused, it
      blocks the reabsorption and metabolism of adenosine normally produced in the
      body, producing the desired effect on the heart, coronary hyperemia. Dipyridamole
      can be used with 201Tl and 99mTc myocardial perfusion tracers, for either planar
      or SPECT imaging, in patients who cannot exercise or who can only exercise at
      submaximal levels.

PMID- 8151404
TI  - Adenosine myocardial perfusion imaging.
AB  - Adenosine myocardial perfusion imaging is useful in diagnosis of coronary artery
      disease (CAD) and risk assessment in patients who have exercise limitations. As a
      pharmacologic stressor, adenosine acts on two cell-surface purine receptors, A1
      and A2. Activation of A2 receptors cause coronary vasodilation. Unlike other
      pharmacologic stressors, such as dipyridamole and dobutamine, adenosine is an
      endogenous biochemical. Adenosine perfusion studies have a relatively high
      sensitivity and specificity (80%-90%) for identifying CAD. Images from adenosine
      studies are comparable to, or better than, images from exercise myocardial
      perfusion studies. The side effects are common, but not serious; they are short
      lived and rarely require the administration of aminophylline.

PMID- 8151405
TI  - Dobutamine myocardial perfusion imaging.
AB  - Dobutamine, a pharmacologic stressor, is useful for myocardial perfusion imaging
      in patients who cannot exercise. Patients with asthma or severe chronic
      obstructive pulmonary disease who are at risk for adverse effects from either
      dipyridamole or adenosine are prime candidates for dobutamine perfusion studies.
      Dobutamine is a predominant beta-1 agonist that increases heart rate, myocardial
      contractility and systolic blood pressure. The sensitivity and specificity of
      dobutamine myocardial perfusion imaging are comparable, for the most part, to
      those from perfusion studies using exercise, dipyridamole or adenosine.

PMID- 8151407
TI  - Myocardial viability assessment.

PMID- 8151406
TI  - The role of clinical data in interpretation of perfusion images.

PMID- 8151408
TI  - Use and limitations of metabolic tracers labeled with positron-emitting
      radionuclides in the identification of viable myocardium.
AB  - Identification of viable myocardium is crucial in identifying patients who could
      benefit from interventional therapy such as coronary artery balloon angioplasty
      or bypass surgery. PET can be used to prospectively identify viable from
      nonviable myocardium based on the pattern of substrate use in comparison with
      perfusion. Viable myocardium can be identified with such diverse tracers as 1-11C
      palmitate (for assessment of fatty acid metabolism) and 18F-fluorodeoxyglucose
      (for assessment of the uptake of glucose). Recent studies have suggested that
      assessment of oxidative metabolism with tracers such as 1-11C-acetate may predict
      with the greatest accuracy segments of myocardial tissue that will recover after
      recanalization. Further studies will be necessary to determine whether PET
      represents a superior technology compared with other more widely available (and
      less expensive) approaches for identification of jeopardized myocardium.
      Nonetheless, PET should provide a better understanding of the pathophysiology of
      myocardial ischemia (since it enables delineation of the biochemical alterations
      that underlie contractile dysfunction) and of therapeutic strategies likely to be
      beneficial. It will also be useful for the identification of viable from
      nonviable myocardium when results of other diagnostic techniques are equivocal,
      and in patients who are at high risk.

PMID- 8151409
TI  - Single-photon perfusion imaging for the assessment of myocardial viability.
AB  - The identification of viable myocardium is an important consideration for patient
      selection prior to interventional procedures, especially in patients with severe
      left ventricular dysfunction. Myocardial perfusion imaging may reflect viability,
      because tracer uptake requires adequate perfusion, cellular integrity and
      metabolic function. The underestimation of myocardial viability noted with
      traditional stress and redistribution thallium imaging has lead to the
      development of alternative protocols to detect viable myocardium, such as late
      (24-hr) imaging and the thallium reinjection method. Rest-redistribution thallium
      imaging may be a useful procedure for predicting recovery of ventricular function
      following revascularization. Quantitative analysis of thallium activity provides
      important information, because mild or moderate defects are usually metabolically
      active as determined by PET. Administration of adjunct medications, such as
      ribose or nitroglycerin, can increase the detection of reversible perfusion
      abnormalities. Technetium-99m perfusion agents offer great promise for perfusion
      imaging, but their role in the detection of myocardial viability is not well
      defined. Underestimation of myocardial viability has been described with 99mTc
      sestamibi scintigraphy; however, use of quantitative perfusion image analysis or
      the addition of functional data provided by gated tomography or first-pass
      imaging may enhance the assessment of viability. Although the optimal method for
      the detection of myocardial viability with single-photon agents is not apparent,
      current methods have substantially improved discrimination between nonviable and
      viable myocardium. In certain instances, however, metabolic imaging with single
      photon fatty acid analogs or positron-emitting radionuclides may be necessary.

PMID- 8151410
TI  - Clinical experience with iodine-123-iodophenylpentadecanoic acid.
AB  - Initial research in dogs and later research in normal volunteers and patients
      with coronary artery disease indicated that 123I-iodophenylpentadecanoic acid
      (IPPA) can provide valuable diagnostic information. This agent compared favorably
      to 201Tl in detecting stenosed coronary arteries and identified reversible
      lesions with greater frequency. Testing with both 201Tl and IPPA before and after
      percutaneous transluminal coronary angioplasty produced similar results,
      supporting the notion that IPPA deserves inclusion among the diagnostic tools
      used to evaluate coronary heart disease.

PMID- 8151411
TI  - Preliminary report of an ongoing phase I/II dose range, safety and efficacy study
      of iodine-123-phenylpentadecanoic acid for the identification of viable
      myocardium.
AB  - An agent that can accurately and cost-effectively identify viable myocardium is
      needed to select the patients most likely to benefit from myocardial
      revascularization. Iodine-123-phenylpentadecanoic acid (IPPA) is a synthetic
      radiolabeled fatty acid that has shown promise in evaluating patients with
      coronary artery disease (CAD). IPPA has unique metabolic properties that may make
      it superior to other single-photon agents used for this task. A Phase I/II study
      is underway to evaluate safety, dose range and efficacy of IPPA in assessing
      viability and predicting functional recovery after revascularization. Patients
      between the ages of 21 and 75 with angiographically documented CAD, who were
      being referred for coronary revascularization, were recruited. The patients were
      randomized to receive 2, 4 or 6 mCi of IPPA and then underwent sequential SPECT
      imaging at 4, 12, 20, 28 and 36 min after injection. Radionuclide
      ventriculography and perfusion imaging were performed before and again 8 wk after
      revascularization. Myocardial metabolic activity of IPPA was analyzed and
      compared to the preinjection and postejection fractions. There were no
      significant adverse effects from the administration of IPPA. Image quality was
      dose-dependent; the 2-mCi dose was not consistently acceptable for quantitative
      analysis. These preliminary data show that IPPA is safe and can produce
      myocardial images of good quality when 4 mCi or more are used. Early results are
      encouraging but more experience will be needed to define the role of IPPA in
      identifying myocardial viability.

PMID- 8151412
TI  - When is myocardial viability an important clinical issue?
AB  - Myocardial viability is a clinically important issue in patients after acute
      myocardial infarction and in patients with left ventricular dysfunction in the
      presence or absence of symptoms. With these broad criteria, roughly 10% to 20% of
      patients with coronary artery disease will be suitable candidates for myocardial
      viability studies. Techniques that predict improvement in regional or global left
      ventricular function must be able to detect hibernating myocardium. The
      improvement observed following coronary revascularization represents a complex
      interaction between compensatory mechanisms, coronary anatomy, surgical outcome
      and patient selection.

PMID- 8151413
TI  - Myocardial viability assessment with dynamic low-dose iodine-123
      iodophenylpentadecanoic acid metabolic imaging: comparison with myocardial biopsy
      and reinjection SPECT thallium after myocardial infarction.
AB  - Aggressive cardiac revascularization requires recognition of stunned and
      hibernating myocardium, and cost considerations may well govern the technique
      used. Dynamic low-dose (1 mCi) [123I]iodophenylpentadecanoic acid (IPPA)
      metabolic imaging is a potential alternative to PET using either 18FDG or 15O
      water. Resting IPPA images were obtained from patients with severe ischemic
      cardiomyopathy, and transmural myocardial biopsies were obtained during coronary
      bypass surgery to confirm viability. Thirty-nine of 43 (91%) biopsies confirmed
      the results of the IPPA images with a sensitivity for viability of 33/36 (92%)
      and a specificity of 6/7 (86%). Postoperatively, wall motion improved in 80% of
      IPPA-viable, dysfunctional segments. Furthermore, when compared to reinjection
      thallium (SPECT-TI) scans after myocardial infarction, IPPA-SPECT-TI concordance
      occurred in 27/35 (77%) (K = 0.536, p = 0.0003). Similar to PET, IPPA
      demonstrated more viability than SPECT-TI, 26/35 (74%) versus 18/35 (51%) (p =
      0.047). Metabolic IPPA cardiac viability imaging is a safe, inexpensive technique
      that may be a useful alternative to PET.

PMID- 8151414
TI  - The clinical utility of echocardiography in the assessment of myocardial
      viability.
AB  - The detection of reversible myocardial dysfunction may be important in patients
      with acute and chronic myocardial dysfunction due to coronary artery disease.
      Assessment for reversible dysfunction may identify high-risk patients who may
      benefit most from aggressive revascularization therapy. Echocardiography has been
      used to identify reversible myocardial dysfunction in both subsets of patients.
      The resting echocardiogram is useful because wall thickening is very predictive
      of viable myocardium. Chamber size, global ventricular function and wall
      thickening can be quantified. Inotropic stimulation by catecholamines or the
      Gregg phenomenon accurately differentiates reversible from fixed dysfunction in
      animal models of myocardial infarction. Clinically, improved wall thickening
      during low-dose dobutamine infusion (dobutamine responsive wall motion) may
      accurately detect reversible dysfunction in both acute and chronic ischemic
      myocardial dysfunction. The accuracy of dobutamine echocardiography has been
      compared to resting planar and SPECT 201Tl scintigraphy and PET. Two studies
      demonstrated that dobutamine responsive wall motion may be as sensitive as
      resting 201Tl SPECT scintigraphy and PET, respectively, for reversible
      dysfunction after acute myocardial infarction. Two other small studies (14
      patients each) demonstrated that dobutamine- responsive wall motion was as
      sensitive as resting quantitative 201Tl planar scintigraphy in patients with
      chronic dysfunction undergoing revascularization.

PMID- 8151415
TI  - Metabolic imaging to assess myocardial viability.
AB  - A potentially reversible impairment of contractile function in patients with
      chronic coronary artery disease characteristically exhibits a regional increase
      in glucose utilization or, more precisely, glucose extraction, as evidenced by
      the presence of a blood flow-glucose metabolism mismatch. The predictive accuracy
      of patterns of blood flow and glucose metabolism has now been established in more
      than 107 patients with 384 dysfunctional myocardial segments against the gold
      standard of myocardial viability, the functional outcome of contractile function
      after revascularization. According to long-term albeit retrospective follow-up
      studies, correlations exist between the blood flow-metabolism patterns and
      patient survival or cardiac morbidity. The same studies point out the high risk
      of patients with blood flow-metabolism mismatches and, at the same time, the
      considerable benefits derived from revascularization, i.e., reduced mortality and
      improvement in symptoms related to congestive heart failure. Imaging of the
      relative distribution of blood flow and of exogenous glucose utilization with PET
      therefore appears to be of considerable value for identifying high-risk patients
      as well as for stratifying patients to the most appropriate therapeutic
      management. This pertains especially to patients with poor left ventricular
      function and symptoms related to congestive heart failure. Assessment of
      myocardial viability in this particular patient group remains diagnostically
      challenging. On the other hand, as demonstrated by several investigations, blood
      flow metabolism imaging with 18F-deoxyglucose and PET is highly accurate in these
      patients for the identification of viable or reversibly dysfunctional myocardium.

PMID- 8151416
TI  - En-couragement versus empowerment.

PMID- 8151417
TI  - Encouragement versus empowerment. A nurse editor responds.

PMID- 8151418
TI  - Encouragement versus empowerment. A nurse executive responds.

PMID- 8151419
TI  - The new AONE.

PMID- 8151420
TI  - The chief nurse executive and intellectual property law. Selected concerns.
AB  - At first, consideration of intellectual property law may seem a remote concern.
      However, CNEs have developed and led the advent of innovative work redesigns,
      unique measurement instruments, patient care documentation tools, and other
      administrative research and teaching originations. Consider intellectual property
      ownership and the rights to use or reproduce that "property" as soon as possible
      to avoid misunderstandings and potential infringements.

PMID- 8151421
TI  - International experiences. Notes and observations.

PMID- 8151422
TI  - The Patient-Driven Interdisciplinary Care Plan.
AB  - Given the paradigm shift to patient-focused care, the Patient-Driven
      Interdisciplinary Care Plan is the next, natural evolutionary step for the
      healthcare industry. The plan, based on four underlying principles, is presented,
      along with preliminary impressions of staff members and patients on one pilot
      unit.

PMID- 8151423
TI  - Unlicensed assistive personnel. Issues relating to delegation and supervision.
AB  - The restructuring of healthcare delivery systems has increased the need for
      professional nurses who are skilled in managing various levels of assistive
      personnel. The authors provide an overview of issues related to supervision and
      delegation and discuss the legal responsibilities of registered nurses when
      delegating nursing care activities to unlicensed assistive personnel.

PMID- 8151424
TI  - The ambulatory treatment unit. An innovative model.
AB  - Changes in the healthcare delivery system have created a competitive marketplace
      that demands new programs to contain healthcare costs while providing more
      efficiently for patients' healthcare needs. One major change is a trend toward
      outpatient ambulatory healthcare. Procedures once performed in the hospital
      currently are done routinely on an outpatient basis. Drug/alcohol treatment
      units, rehabilitation centers, and occupational health centers provide long-term
      care on an outpatient basis. Home healthcare programs provide nursing services
      for patients who are chronically ill and for those with special recovery needs
      after discharge; hospice programs provide nursing care for terminally ill
      patients. Although change can be unsettling, it also provides new opportunities
      for nursing to be creative and innovative in providing client services that meet
      present demands. This article presents one such innovation, the development of an
      ambulatory treatment unit.

PMID- 8151426
TI  - Information technology as a proactive strategic weapon in healthcare.

PMID- 8151425
TI  - Discharge planning. A study of nursing staff involvement.
AB  - Discharge planning places the nurse in a pivotal position in the care process. In
      this study, although most nurses acknowledged the importance of a nursing
      leadership role in the discharge-planning process, many were confused about how
      discharge planning was accomplished in their hospitals. Feedback about
      effectiveness of discharge planning was almost nonexistent, and resources were
      not easily accessible. Nurses must become more effective in this role. Nursing
      administrators must establish organization mechanisms to encourage nursing
      participation in discharge planning, and provide ongoing support.

PMID- 8151427
TI  - A transformational model for the practice of professional nursing. Part 1, The
      model.
AB  - Our healthcare system is undergoing major transformation. Most nurse executives
      know that change is necessary and inevitable, but are less certain how to
      position their departments for these changes. The Transformational Model for the
      Practice of Professional Nursing was developed as a "road map" for that purpose.
      Part 1 of the model discusses the paradigm shifts that need to occur in
      professional practice for future success. The various components of the model are
      presented, and applications are identified. Part 2 will appear in the May 1994
      issue of JONA, and will discuss the implementation of this model into a practice
      setting.

PMID- 8151428
TI  - Total quality management: a feminist perspective.

PMID- 8151429
TI  - Reputational shared governance.

PMID- 8151430
TI  - How to write a winning research proposal. Strategies for nursing executives.

PMID- 8151431
TI  - Changes in nursing administration research priorities. A sign of the times.
AB  - Although research is the critical element in the advancement of knowledge, for
      research to contribute knowledge to the practice of nursing it must be focused on
      subjects germane to the practice arena. When the focus of research in a
      discipline is not congruent with the needs of the discipline, knowledge
      development is compromised. By comparing the aforementioned retrospective
      research reviews to the research priority lists, we see that published research
      in nursing administration has not been tied closely to identified priorities.
      Healthcare reform provides nursing administration with a renewed opportunity to
      focus its research on priority areas. With the implementation of healthcare
      reforms, the practice arena for nursing and nursing administration will shift
      from the acute care setting to community and home-based settings, necessitating a
      shift in research to address these new delivery settings and the required care
      systems. The priorities generated from the national consensus group represent
      that shift, and may provide meaningful foci for future nursing administration
      research.

PMID- 8151432
TI  - Data needs for decision support of chief nurse executives.
AB  - The dynamic changes in healthcare require accurate data on which chief nurse
      executives can base their decisions. Once these data are available, they must be
      organized efficiently to assist with decision making. The author presents the
      results from a national Delphi study, in which data elements for the decision
      support of chief nurse executives were delineated.

PMID- 8151433
TI  - Benefits of hospital information systems as seen by front-line nurses and general
      hospital staff.
AB  - A series of descriptive correlation studies involving 6 hospitals and 697
      respondents identified the benefits of computerized hospital information systems
      (HIS) and the value of those benefits as perceived by front-line system users.
      Benefits related to quality of care were realized to a greater extent, and
      considered more important, than those related to cost/savings/productivity or
      professionalism/recruitment/retention. Perceptions of nurses were not
      significantly different from those of general hospital staff members. Scattered
      significant correlations were revealed between demographic and organization
      variables and perceptions of benefits.

PMID- 8151434
TI  - Using an interview guide to identify effective nurse managers. Phase 1,
      Qualitative tool construction and testing.
AB  - Hiring effective nurse managers is key to the success of today's healthcare
      institutions. The authors describe the development of a pre-employment interview
      guide to assist in the selection process of nurse managers. Characteristics and
      competencies of effective nurse managers are delineated from the qualitative
      data.

PMID- 8151435
TI  - Staff nurse perception of job empowerment and organizational commitment. A test
      of Kanter's theory of structural power in organizations.
AB  - In this study, Rosabeth Kanter's structural theory of organizational behavior was
      tested in a nursing population by examining the relationship between 161 staff
      nurses' perceived job empowerment and their commitment to the organization. Data
      were collected using the Organizational Description Opinionnaire, the
      Organizational Commitment Questionnaire, a modified version of the Conditions for
      Work Effectiveness Questionnaire, and a demographic questionnaire. Consistent
      with Kanter's theory, a strong positive relationship was found between nurses'
      perceptions of power and opportunity and their commitment to the organization. In
      addition, overall empowerment was correlated positively with nurses' perceptions
      of their immediate managers' power. The results suggest that nurse administrators
      can empower their staff and improve organizational commitment by manipulating the
      structures in the work environment to allow greater access to the power and
      opportunity structures that Kanter maintains are important to overall work
      effectiveness.

PMID- 8151436
TI  - Nurse manager competencies.
AB  - First-line nurse managers play a critical management role because they greatly
      influence the success of healthcare organizations. Several studies have profiled
      the first-line nurse manager, but have focused on the characteristics and
      responsibilities of these individuals. This study delineated and identified
      specific behavioral competencies that are considered important for hospital-based
      nurse manager effectiveness. The results of the survey are relevant for the
      selection, preparation, and development of effective hospital-based nurse
      managers.

PMID- 8151437
TI  - Technological and environmental characteristics of intensive care units.
      Implications for job redesign.
AB  - Nurse executives are experiencing severe pressures to create systems of care
      delivery that provide services in more cost-conscious ways. Before care systems
      can be restructured, a systematic assessment of the work and the environment of
      the nursing unit must take place. This study found significant differences among
      nine intensive care units regarding both the nature of their work and their
      environments. These differences provided information that can be used in staffing
      decisions, nurse/physician interaction, and staff nurse and managerial
      recruitment.

PMID- 8151438
TI  - Mohs' micrographic surgery and prompt reconstruction for basal cell carcinoma:
      report of 62 cases using the combined method.
AB  - Aggressive, recurrent, and difficult to manage skin cancers may require complex
      solutions. In this review of 62 skin cancers, we demonstrate a novel approach to
      the management of these tumors. Mohs' micrographic surgery was used to remove the
      tumor, and was followed by immediate or delayed plastic surgical repair. Using
      this combined method, the highest attainable cure rate is linked with a
      coordinated prompt cosmetic repair. In this series of 54 patients with 62 skin
      cancers, there was one recurrence with a follow-up of one to four years. Most
      cases (65%) involved reconstruction within ten days of tumor removal. Eighty-one
      percent had a single-stage reconstruction. In seventeen patients, new tumors
      developed at other sites during the four-year follow-up period. On the basis of
      our experience with this combined method, we feel that Mohs' surgery, coordinated
      with prompt plastic repair, offers distinct advantages in the management of
      difficult skin cancers.

PMID- 8151439
TI  - Percutaneous discectomy.
AB  - 1. In patients with symptomatic lumbar disc herniations contained within the
      interspace, the percutaneous automated discectomy is a reasonable option to open
      operative procedures. The results appear to be comparable in either case. 2. The
      procedure is done under local anesthesia, thus avoiding a general anesthetic, and
      has a shorter and less painful postoperative recovery period. 3. The
      complications and morbidity from the percutaneous technique appear to be
      significantly less than the open surgical techniques. 4. Proper selection of
      surgical candidates is extremely important in any surgical approach to the
      treatment of lumbar degenerative disc disease. Patients who have had a prior
      lumbar surgery (or "redo" cases) do not appear to do well with percutaneous
      discectomy. 5. As demonstrated in many other studies, the workers'
      compensation/liability patients did not fare as well as "standard" patients. 6.
      Since the original study, we have performed an additional 50 automated
      percutaneous discectomies and 52 laser discectomies (totaling 212 cases in all).
      7. Although the sample size is small, and our experience is limited, patients
      treated with laser discectomy appear to be experiencing a higher percentage of
      favorable results than patients treated with automated percutaneous discectomy.

PMID- 8151441
TI  - State's durable medical equipment claims now going to regional carrier.

PMID- 8151440
TI  - Jungle medicine. An Oklahoma medical team visits Mexico.

PMID- 8151443
TI  - Back to the marketplace!

PMID- 8151442
TI  - Compression brachial plexopathy caused by chronic posterior dislocation of the
      sternoclavicular joint.
AB  - Thoracic outlet syndrome developed in a patient due to chronic posterior
      dislocation of the sternoclavicular joint, following an all-terrain vehicle
      accident. Decompression of the thoracic outlet was accomplished by surgical
      reduction of the clavicle, excision of the medial clavicle and reconstruction of
      the costoclavicular ligament. The patient's symptomatology was relieved by the
      surgical procedure performed.

PMID- 8151444
TI  - Liver transplantation following preoperative closure of intrapulmonary shunts.
AB  - Intrapulmonary shunts producing basal resting hypoxemia and necessitating the
      continual use of supplemental oxygen by two cirrhotic men were closed prior to
      liver transplantation with octreotide acetate, a somatostatin analogue. The
      closure of these shunts was monitored by serial blood gas determinations and
      shunt estimations using two different techniques. Partial closure of the shunts
      with preoperative octreotide acetate administration allowed liver transplantation
      to proceed with successful engraftment and eventual permanent closure of the
      shunts. Currently, both patients are alive and well with normal liver function
      and blood gases and, most important, have no requirement for supplemental oxygen.

PMID- 8151445
TI  - Tuberculosis in a Tulsa high school.
AB  - Following the discovery of a high school student with communicable tuberculosis,
      the Tulsa City-County Health Department skin tested 1,005 persons in the family,
      community, and school. Of the 931 persons tested at the school, 10 were reactors
      in March and 33 more were reactors in May. All 5 family members and 4 community
      contacts were tuberculin reactive. In all, 52 new tuberculin reactors were
      identified, evaluated, and considered for treatment or prophylaxis. This
      situation illustrates the conundrum that tuberculosis remains an important public
      health issue because of the possibility of transmission from small pockets of
      diseased persons to the larger community, especially in institutions of all
      kinds. Physicians and public health agencies must be vigilant and identify new
      cases for treatment and begin contact tracing to minimize the spread of
      tuberculosis.

PMID- 8151446
TI  - Surgery for angina pectoris: a historical perspective.
AB  - Coronary artery disease continues to be the major cause of death in the United
      States each year with close to 1 million people dying of this disease annually,
      one third of those being under the age of 65. An estimated 5 million people in
      this country suffer some degree of disability from angina pectoris.

PMID- 8151447
TI  - Treatment of arrow wounds in the American Indian-Fighting Army: the technique of
      Brevet Lt. Col. Joseph H. Bill.
AB  - The history of medicine contains many chapters with seemingly insoluble problems
      that were overcome by great innovators. Contributors like Pasteur, Reed, and Salk
      altered the practice of medicine forever. However, along with the giants of
      medicine, there have been legions of other physicians who have made lesser, but
      not unimportant contributions. Many of these discoveries involved techniques that
      became obsolete as technology progressed, and many others formed the basis for
      further medical advances. Such was the case of Dr. Joseph H. Bill's technique of
      treating arrow wounds in the Indian Fighting Army of 1866-1890.

PMID- 8151448
TI  - Pitfalls in metabolic screening.

PMID- 8151449
TI  - Early orthodontic treatment: an adjunctive appliance.

PMID- 8151451
TI  - Successful financial arrangements: a team approach.

PMID- 8151450
TI  - Everything you ever wanted to know about peer review ... but were afraid to ask.

PMID- 8151452
TI  - The specific effects of 8-methoxypsoralen photoadducts on cell growth: HPLC
      analysis of monoadduct and crosslink formation in cells exposed to split-dose
      treatment.
AB  - The effects of 8-methoxypsoralen (8-MOP) monoadducts and crosslinks on growth and
      viability of mastocytoma cells were investigated. To induce monoadduct formation
      (4',5'-monoadducts and 3,4-monoadducts), the cells were incubated with 8-MOP (1
      microgram ml-1) and exposed to 419 nm radiation, resulting in the formation of
      more than 96% monoadducts. After washing and resuspension, the cells were exposed
      to a small dose of long-wavelength UV radiation (UVA, 2 J cm-2) to convert
      monoadducts into crosslinks. Similar adduct levels were obtained after either 8
      MOP plus visible light treatment or 8-MOP plus split-dose protocol. Cells treated
      with 419 nm light resumed normal growth rates more rapidly than cells which also
      received the UVA dose. High performance liquid chromatography (HPLC) analysis of
      DNA obtained from each group of cells showed that the UVA step resulted in an
      increase in crosslinks from 3.2% after 419 nm radiation to 56.5% after UVA
      irradiation.

PMID- 8151453
TI  - Relationship between the ability of sunscreens containing 2-ethylhexyl-4'
      methoxycinnamate to protect against UVR-induced inflammation, depletion of
      epidermal Langerhans (Ia+) cells and suppression of alloactivating capacity of
      murine skin in vivo.
AB  - The UVB sunscreen 2-ethylhexyl-4'-methoxycinnamate was evaluated in hairless
      albino mouse skin for its ability to inhibit UVR-induced (i) oedema, (ii)
      epidermal Langerhans cell (Ia+) depletion and (iii) suppression of the
      alloactivating capacity of epidermal cells (mixed epidermal cell-lymphocyte
      reaction, MECLR). The sunscreen, prepared at 9% in ethanol or a cosmetic lotion,
      was applied prior to UVB/UVA irradiation. In some experiments there was a second
      application halfway through the irradiation. Single applications in both vehicles
      gave varying degrees of protection from oedema and Langerhans cell depletion but
      afforded no protection from suppression of MECLR. When the sunscreens were
      applied twice there was improved protection from oedema and Langerhans cell
      depletion and complete protection was afforded from suppression of MECLR. There
      was a clear linear relationship between Langerhans cell numbers and oedema with
      and without sunscreen application. The relationship between Langerhans cell
      numbers and MECLR was more complex. These data confirm published discrepancies
      between protection from oedema (a model for human erythema) and endpoints with
      immunological significance, but show that 2-ethylhexyl-4'-methoxycinnamate can
      afford complete immunoprotection, although protection is dependent on the
      application rate and vehicle.

PMID- 8151454
TI  - Photodynamic inactivation of herpes viruses with phthalocyanine derivatives.
AB  - The antiviral photosensitization capacity of 11 different phthalocyanine (Pc)
      derivatives was examined using herpes simplex virus-1, herpes simplex virus-2 and
      varicella zoster virus in the search for the most potent sensitizers for viral
      decontamination of blood. The kinetics of viral photoinactivation were resolved
      during the stages of viral adsorption and penetration into the host cells. The
      capacity of Pc in the photodynamic inactivation of viruses was compared with that
      of merocyanine 540 (MC540), another widely studied photosensitizer. Sensitivity
      to photoinactivation decreased progressively with time after addition of viruses
      to their host cells. The viruses were most sensitive to photodynamic inactivation
      up to 30 min from the initiation of adsorption. Cell-associated viruses, 45-60
      min after the onset of adsorption, are highly resistant to photodynamic treatment
      by most photosensitizers, with the exception of amphiphilic Pc derivatives. Thus
      the mixed sulfonated Pc-naphthalocyanine derivatives AlNSB3P and AlN2SB2P
      demonstrated a remarkable decontamination activity even 60 min after the onset of
      adsorption. Ultrastructural examination of these photosensitized viruses
      demonstrated damage to the viral envelope which prevented viral adsorption and/or
      penetration. The non-enveloped adenovirus was found to be resistant to all the
      dyes tested.

PMID- 8151455
TI  - Photophysical characterization of hematoporphyrin incorporated within collagen
      gels.
AB  - Physical properties of hematoporphyrin-enriched collagen gels relevant to the
      photodynamic treatment of cancer are characterized. The incorporation of the
      sensitizer within the gels does not affect either the structure of the gel or the
      absorption and fluorescence spectra of the sensitizer. The gel-embedded
      sensitizer photodegrades efficiently with the formation of a product emitting
      near 635 nm. Differences in the collagen scattering are observed following
      sensitization vs. prolonged irradiation with Ar+ laser, indicating contrasting
      structural modifications effected to the biopolymer matrix in the two cases. The
      results correspond well to in vivo observations, suggesting that hematoporphyrin
      enriched collagen gels may be appropriate systems for modeling the influence of
      the semisolid nature of tissues, and in particular of the tumour stroma collagen,
      on the photodynamic phenomenon.

PMID- 8151456
TI  - Photosensitized cross-linking and cleavage of pBR322 and M13 DNA: comparison of
      4,4',6-trimethylangelicin and 3-carbethoxypsoralen.
AB  - The furocourmarins 3-carbethoxypsoralen (3-CP) and 4,4',6-trimethylangelicin
      (TMA) were generally believed to be incapable of cross-linking DNA upon
      irradiation with ultraviolet light. Denaturation of photosensitized pBR322 DNA,
      either supercoiled or previously linearized with a restriction enzyme, proved
      that 3-CP was indeed monofunctional, but that TMA produced cross-links. Identical
      conclusions were reached with double stranded M13 DNA which had been linearized
      with EcoR 1. Both sensitizers also induced partial DNA cleavage. In contrast to 3
      CP, photosensitization with TMA made the DNA resistant to enzymatic cleavage.

PMID- 8151457
TI  - Continuous dosimetry of the biologically harmful UV-radiation in Antarctica with
      the biofilm technique.
AB  - For the first time, a continuous biological dosimetry experiment for cytotoxic
      solar UV-radiation has been performed in Antarctica. The biologically harmful UV
      radiation on the ground was measured at the German Antarctic Georg von Neumayer
      Station (70 degrees 37' S, 80 degrees 22' W) from December 1990 to March 1992
      using the biofilm technique. The UV-sensitive targets were dried spores of
      Bacillus subtilis which were immobilized on the film surface. The UV-induced
      inhibition of biological activity, determined photometrically from the protein
      synthesized after incubation and staining, was taken as a measure for the
      absorbed UV-dose. Films were exposed in horizontal position for time intervals
      ranging from 4 days during summer up to 51 and 41 days before and after the polar
      night respectively. The use of different cut-off filters allowed the calculation
      of the biologically effective UVA, UVB and the complete UV-radiation (UVA + B).
      The data were compared with the global radiation and the ozone column thickness
      indicating an increase of biologically harmful UVB radiation during austral
      spring at reduced ozone concentrations yielding a radiation amplification factor
      (RAF) of 1.4, whereas for the total UV(A + B) range the RAF amounted to 0.3.

PMID- 8151458
TI  - What kind of radiation is efficient in solaria, UVA or UVB?

PMID- 8151459
TI  - Photobiological activity of sulphur and selenium analogues of psoralen.
AB  - Eight psoralen analogues, in which sulphur or selenium replaces one or both
      intracyclic oxygen atoms, were synthesized. Photoreaction with M13mp19 RF DNA in
      the presence and absence of oxygen (wavelength, greater than 320 nm) was studied.
      The damaged viral DNA was transfected into Escherichia coli and scored for
      infectivity towards Ca-treated wild-type E. coli. This allowed a comparative
      evaluation to be made of the heteropsoralens in terms of the photoreaction with
      DNA and the photodynamic effect. Most of the seleno- and thio-psoralens show very
      high photoactivity towards DNA compared with psoralen and 8-methoxypsoralen (8
      MOP). Their photoreactivity is due mainly to a [2 + 2] photoreaction, since only
      a minor influence of molecular oxygen could be detected. Some of the studied
      seleno- and thio-psoralens are very efficient DNA photoinactivating agents and
      show great promise in photochemotherapy.

PMID- 8151460
TI  - Neurofibromatosis type 1: the cognitive phenotype.
AB  - Visuospatial deficits have been reported in patients with neurofibromatosis type
      1 (NF 1), although detailed observations regarding academic achievement are
      conflicting. Using neurocognitive testing and magnetic resonance imaging, we
      studied 12 families, each comprising one child with NF 1, an unaffected sibling
      of the same age range (6 to 16 years), and both biologic parents. The Full Scale
      IQ ranged from 70 to 130 among children with NF 1 and from 99 to 139 among
      unaffected siblings. A significant (p < 0.01) pairwise difference was found
      between each child with NF 1 and sibling on the Full Scale IQ and the Verbal IQ.
      On a single visuospatial test, Judgement of Line Orientation, children with NF 1
      did significantly worse than siblings (p < 0.01). Children with NF 1 had
      significant learning disabilities in written language and reading (p < 0.05) and
      in neuromotor dysfunction (p < 0.005) compared with siblings. A significant
      correlation was found between the pairwise lowering of the Full Scale IQ and
      Judgment of Line Orientation scores in children with NF 1 and the number of
      locations in which, on magnetic resonance imaging, T2-weighted hyperintensities
      were seen (Full Scale IQ: p < 0.0003; Judgment of Line Orientation score: p <
      0.02). We conclude that NF 1 is associated with a significantly lower Full Scale
      IQ, multifocal cognitive deficits (Verbal IQ, Judgment of Line Orientation
      score), reading disability, and neuromotor deficit. Pairwise cognitive
      differences correlated with the number of brain lesions on magnetic resonance
      imaging.

PMID- 8151461
TI  - Biology and treatment of acute lymphoblastic leukemia.

PMID- 8151462
TI  - Intramuscular versus oral antibiotic therapy for the prevention of meningitis and
      other bacterial sequelae in young, febrile children at risk for occult
      bacteremia.
AB  - Because studies of the treatment of children with occult bacteremia have yielded
      conflicting results, we compared ceftriaxone with amoxicillin for therapy.
      Inclusion criteria were age 3 to 36 months, temperature > or = 39 degrees C, an
      acute febrile illness with no focal findings or with otitis media (6/10 centers),
      and culture of blood. Subjects were randomly assigned to receive either
      ceftriaxone, 50 mg/kg intramuscularly, or amoxicillin, 20 mg/kg/dose orally for
      six doses. Of 6733 patients enrolled, 195 had bacteremia and 192 were evaluable:
      164 Streptococcus pneumoniae, 9 Haemophilus influenzae type b, 7 Salmonella, 2
      Neisseria meningitidis, and 10 other. After treatment, three patients receiving
      amoxicillin had the same organism isolated from their blood (two H. influenzae
      type b, one Salmonella) and two from the spinal fluid (two H. influenzae type b),
      compared with none given ceftriaxone. Probable or definite infections occurred in
      three children treated with ceftriaxone and six given amoxicillin (adjusted odds
      ratio 0.43, 95% confidence interval 0.08 to 1.82, p = 0.31). The five children
      with definite bacterial infections (three meningitis, one pneumonia, one sepsis)
      received amoxicillin (adjusted odds ratio 0.00, 95% confidence interval 0.00 to
      0.52, p = 0.02). Fever persisted less often with ceftriaxone (adjusted odds ratio
      0.52, 95% confidence interval 0.28 to 0.94, p = 0.04). Although the difference in
      total infections was not significant, ceftriaxone eradicated bacteremia,
      prevented significantly more definite focal bacterial complications, and was
      associated with less persistent fever.

PMID- 8151463
TI  - Pyuria and bacteriuria in urine specimens obtained by catheter from young
      children with fever.
AB  - Results of urinalysis and culture of 2181 urine specimens obtained by catheter
      from febrile children aged less than 24 months were analyzed to determine the
      following: (1) an optimal cutoff point in considering a bacterial colony count
      clinically "significant," (2) the accuracy of leukocyte esterase and nitrite
      tests in identification of pyuria and bacteriuria, and (3) the utility of pyuria
      (defined as > or = 10 leukocytes/mm3) in the discrimination of urinary tract
      infection from asymptomatic bacteriuria. Among 110 urine cultures with > or =
      10,000 colony-forming units per milliliter, 92 (84%) had > or = 100,000 CFU/ml,
      10 (9%) had 50,000 to 99,000 CFU/CFU/ml and 8 (7%) had 10,000 to 49,000 CFU/ml.
      Urine specimens with 1000 to 49,000 CFU/ml were more likely than specimens with >
      or = 50,000 CFU/ml to yield Gram-positive or mixed organisms (36/60 vs 7/109; p <
      0.001). A count of < 10 leukocytes/mm3 was almost invariably associated with a
      sterile culture; a count of > or = 10 leukocytes/mm3 was found in 93 of 102
      patients with > or = 50,000 CFU/ml. The dipstick leukocyte esterase test had
      sensitivities of 52.9% and 66.7% in detecting > or = 10 leukocytes/mm3 and > or =
      20 leukocytes/mm3, respectively. The dipstick nitrite test had a sensitivity of
      31.4% in detecting bacteriuria (> or = 50,000 CFU/ml). Acute pyelonephritis was
      diagnosed by a renal scan with dimercaptosuccinic acid labeled with technetium
      99m in 50 (77%) of 65 patients with > or = 10 leukocytes/mm3 but in none of five
      patients with < 10 leukocytes/mm3 (p < 0.01). The findings in these five patients
      were consistent with colonization of the urinary tract rather than infection. For
      urine specimens obtained by catheter, we believe that urinary tract infection is
      best defined by both a leukocyte count > or 10/mm3 and a CFU count > or =
      50,000/ml. This definition almost always discriminates among true urinary tract
      infection, bacteriuria resulting from contamination of the urine specimen, and
      asymptomatic bacteriuria.

PMID- 8151464
TI  - A prospective, double-blind study of growth failure in children with chronic
      renal insufficiency and the effectiveness of treatment with calcitriol versus
      dihydrotachysterol. The Growth Failure in Children with Renal Diseases
      Investigators.
AB  - Because controlled trials in adults have shown accelerated deterioration of renal
      function in a small number of patients receiving calcitriol for renal
      osteodystrophy, we initiated a prospective, randomized, double-blind study of the
      use of calcitriol versus dihydrotachysterol in children with chronic renal
      insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated
      glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with
      elevated serum parathyroid hormone concentrations. Ninety-four patients completed
      a mean of 8.0 months of control observations and were randomly assigned to a
      treatment period; 82 completed the treatment period of at least 6 months while
      receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a
      dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment
      the height z scores for both calcitriol- and dihydrotachysterol-treated groups
      showed no differences between the two groups. In relation to cumulative dose,
      there was a significant decrease in glomerular filtration rate for both
      calcitriol and dihydrotachysterol; for calcitriol the rate of decline was
      significantly steeper (p = 0.0026). The treatment groups did not differ
      significantly with respect to the incidence of hypercalcemia (serum calcium
      concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of
      renal function is mandatory during the use of either calcitriol or
      dihydrotachysterol because both agents were associated with significant declines
      in renal function. There was no significant difference between calcitriol and
      dihydrotachysterol in promoting linear growth or causing hypercalcemia in
      children with chronic renal insufficiency. Dihydrotachysterol, the less costly
      agent, can be used with equal efficacy.

PMID- 8151465
TI  - Renal acidification in children with idiopathic hypercalciuria.
AB  - Distal renal tubular acidosis is frequently associated with hypercalciuria. To
      further investigate the cause-and-effect relationships between the two
      conditions, we examined 20 children (5 to 18 years of age) with idiopathic
      hypercalciuria for evidence of renal tubular acidosis. Serum electrolytes and
      urine citrate levels were normal in all subjects. After a single dose of
      furosemide, 1 of the 20 subjects did not show a decrease in urine pH < 5.5, which
      suggests an acidification defect in the cortical collecting duct. Three other
      patients failed to show an increase in urine-minus-blood partial pressure of
      carbon dioxide > 20 mmHg after urine alkalinization with orally administered
      acetazolamide, a finding compatible with a rate-dependent distal renal tubular
      acidosis. These four subjects underwent acute acid loading with arginine
      hydrochloride. In all four subjects urine pH decreased < 5.5 but urinary ammonium
      excretion failed to increase normally; this supports the diagnosis of a defect in
      distal acidification. Four of six patients with nephrolithiasis had evidence of
      distal renal tubular acidosis, in contrast to none of the 14 patients without
      stones (p = 0.003). We conclude that distal acidification abilities seem to be
      intact in children with hypercalciuria in the absence of nephrolithiasis. We
      speculate that calcium precipitation may lead to tubular damage, including distal
      renal tubular acidosis.

PMID- 8151466
TI  - Ultrasonographic diagnosis of juvenile colonic polyps.
AB  - To reduce the risks of air-contrast barium enemas and colonoscopy, we studied the
      use of saline enemas for ultrasonographic examination of children with rectal
      bleeding. Thirty-nine children, from 2 years 8 months to 8 years 3 months of age,
      were examined. Juvenile colonic polyps were ultrasonographically demonstrated and
      histologically confirmed in 25 children; all the polyps were solitary and
      pedunculated, and were located in the splenic flexure in 3 children, the
      descending colon in 6, the sigmoid colon in 12, and the rectum in 4.
      Ultrasonographic findings by hydrocolonic ultrasonography were identical to those
      obtained by immersion ultrasonography of removed specimens. Hypoechoic areas
      within more hyperechoic polyps were shown histologically to be dilated glandular
      canals. The 14 children in whom no abnormal ultrasonographic findings were shown
      had no further rectal bleeding after resuming regular defecation, and 5 of these
      14 had negative colonoscopic findings. No adverse reactions were noted in any
      child during or after the saline enema examination. We conclude that
      ultrasonographic examination with a saline enema is a safe and accurate method of
      assessing children with rectal bleeding, especially for the diagnosis of juvenile
      colonic polyps.

PMID- 8151467
TI  - Small intestinal glucoamylase deficiency and starch malabsorption: a newly
      recognized alpha-glucosidase deficiency in children.
AB  - To determine the prevalence of short polymers of glucose and starch malabsorption
      caused by small intestinal glucoamylase deficiency in children with chronic
      diarrhea, we studied small bowel biopsy specimens from 511 children (aged 1 month
      to 9 years) with chronic diarrhea evaluated at 54 medical centers. Glucoamylase
      and disaccharidase (lactase, sucrase, maltase, and palatinase) enzyme assays were
      performed. Of the 511 children, 15 had glucoamylase deficiency. Six who had
      significant small intestinal mucosal injury and disaccharidase deficiencies were
      defined as having secondary glucoamylase deficiency; the other nine patients with
      normal mucosal morphologic features were defined as having primary glucoamylase
      deficiency. Secretin tests showed normal pancreatic amylase values for age in all
      seven children tested. Four of them had abnormal findings on tolerance tests for
      starch and short polymers of glucose (rise in blood glucose concentration: < 20
      mg/dl) and reducing substances in stools, and three of these four had symptoms of
      intolerance (abdominal distention, flatulence, and diarrhea). All seven patients
      responded to a starch elimination diet. After reintroduction of a starch diet,
      diarrhea recurred in four patients; this was alleviated 48 hours after
      reelimination of starch. We conclude that intestinal glucoamylase deficiency is
      present in some patients with chronic diarrhea.

PMID- 8151468
TI  - Prevalence of stress hyperglycemia among patients attending a pediatric emergency
      department.
AB  - OBJECTIVE: To determine the prevalence and clinical characteristics associated
      with stress hyperglycemia among children and adolescents attending a pediatric
      emergency department. DESIGN: Patients who required a venipuncture for evaluation
      of an acute illness or injury from October 1992 to March 1993 in an urban
      pediatric emergency department were enrolled and screened prospectively for
      hyperglycemia (glucose level > or = 8.3 mmol/L; > or = 150 mg/dl). Data were
      collected regarding demographic characteristics, history, clinical findings, and
      admission status. RESULTS: A total of 926 patients ranging in age from 3 days to
      21 years were enrolled. Blood glucose values ranged from 1.94 mmol/L (35 mg/L) to
      14.65 mmol/L (264 mg/dl); 35 patients (3.8%) had hyperglycemia. The prevalence of
      stress hyperglycemia was significantly increased among patients if they (1) had
      temperatures greater than 39.5 degrees C (9.3%) versus normal temperatures (2.8%)
      (p < 0.001), (2) had been admitted to a critical care unit of the hospital
      (24.1%) or to any hospital unit (4.4%) versus not having been admitted (2.6%) (p
      < 0.001), and (3) had received fluids intravenously (6.0%) versus having received
      no fluids intravenously (2.7%) (p = 0.014). CONCLUSIONS: Stress hyperglycemia is
      a frequent clinical occurrence in a pediatric emergency department. It does not
      appear to be associated with a particular diagnostic category but is
      significantly associated with severity of illness as measured by elevated
      temperature, hospital admission, and hydration status.

PMID- 8151469
TI  - Accuracy of the clinical examination in detecting hypoxemia in infants with
      respiratory illness.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of the clinical examination in
      detecting hypoxemia in infants with lower respiratory tract illness. DESIGN:
      Cross-sectional study. SETTING: Three university pediatric outpatient departments
      and one private pediatric practice. PATIENTS: Healthy infants less than 1 year of
      age seen between December and March 1989 and 1990, with symptoms suggesting acute
      lower respiratory tract illness. MAIN OUTCOME MEASURES: The test characteristics
      of 27 elements of the clinical examination, as well as the accuracy of the
      overall examination and the components of the examination in detecting oxygen
      saturation < 95% measured by pulse oximetry. Reliability of clinical examination
      findings. RESULTS: None of the 27 clinical findings had sensitivities that would
      make them useful diagnostic tests for hypoxemia. By combining all the clinical
      findings, however, we found good diagnostic accuracy (area under the receiver
      operator characteristic curve 0.90). Three groups of clinical findings--social
      interactiveness, respiratory effort, and physical appearance--accounted for much
      of the diagnostic accuracy of the examination. Auscultatory findings contributed
      little. In these three groups, five clinical findings accounted for almost all
      the accuracy: attentiveness, consolability, respiratory effort, color, and
      movement. Together, these findings also had good accuracy (area under the
      receiver operator characteristic curve 0.95). CONCLUSIONS: A small number of
      clinical observations may be mostly responsible for the diagnostic value of the
      clinical examination of infants with symptoms of LRI. Concentrating on a limited
      group of findings appears to enhance the accuracy of the examination in detecting
      hypoxemia.

PMID- 8151470
TI  - Immune responses to the Escherichia coli dnaJ heat shock protein in juvenile
      rheumatoid arthritis and their correlation with disease activity.
AB  - Patients with juvenile rheumatoid arthritis frequently have abnormal immune
      responses to the hsp65 class of bacterial heat shock proteins. However,
      lymphocytes from children with other inflammatory diseases may also recognize
      hsp65, and the role of these antigens in juvenile rheumatoid arthritis remains
      controversial. We have studied humoral and cellular immune responses to a
      distinct, recently described bacterial heat shock protein, designated dnaJ. The
      Escherichia coli dnaJ gene was cloned and expressed, and the purified recombinant
      protein was used as an antigen. Neither normal children nor children with various
      chronic inflammatory diseases had lymphocyte proliferative responses to
      recombinant dnaJ. However, lymphocytes from patients with polyarticular,
      pauciarticular, and systemic manifestations of juvenile rheumatoid arthritis
      responded strongly to the antigen. Cellular immune responses to dnaJ were higher
      in synovial fluid than in blood and higher in children with active disease than
      in children in remission. These data show that increased immune reactivity to
      dnaJ is characteristic of juvenile rheumatoid arthritis and that the magnitude of
      the immune response is linked to disease activity. The results suggest that an
      abnormal immune response to antigens on commensal gut bacteria may contribute to
      the generation of chronic inflammation in juvenile rheumatoid arthritis.

PMID- 8151471
TI  - Immunoglobulin A subclasses in infants' saliva and in saliva and milk from their
      mothers.
AB  - We sought to determine (1) the ontogeny of secretory IgA subclasses in saliva of
      breast- and formula-fed infants and (2) the influence of breast-feeding on the
      maturation of secretory salivary IgA subclasses. Secretory IgA and subclasses 1
      and 2 concentrations were determined in saliva from 40 healthy, term infants from
      birth to age 18 months, and in parallel milk samples from the infants' mothers
      who were breast-feeding during the first 6 months after birth. Secretory IgA was
      detected in the neonates' saliva as early as 3 days after birth, increased
      rapidly during the next 6 months, but then stabilized at a level approximately
      one-sixth that of the mothers' salivary secretory IgA. Secretory IgA2 represented
      less than 15% of secretory IgA in saliva collected 2 weeks after birth but by 6
      months represented 24.4% of secretory IgA, a value approaching that of the
      mothers' salivary secretory IgA2 (30.4%). This increase in the proportion of
      secretory IgA2 was temporally related to a reduction in the proportion of
      secretory IgA2 in milk throughout lactation. The secretory IgA concentration
      increased more rapidly during the first 6 months after birth in infants
      exclusively breast fed than in those exclusively bottle fed. We conclude that
      although secretory immunity is immature in infants, breast-feeding may aid in
      protection against pathogenic microorganisms by increasing the rate of mucosal
      IgA maturation.

PMID- 8151472
TI  - Risk factors for seizure recurrence in children with febrile seizures: a pooled
      analysis of individual patient data from five studies.
AB  - To reassess the relations between postulated risk factors and seizure recurrence
      after a first febrile seizure (FS), the individual data from five follow-up
      studies that used similar definitions of FSs and risk factors were pooled and
      reanalyzed. The risk of frequent recurrent seizures and of the occurrence of
      complex seizures in previously healthy, untreated children was studied. Seizure
      recurrence hazard was described as a function of the child's attained age. The
      influence of various risk factors on the recurrence hazard was assessed, with
      control for other factors. Of a total of 2496 children with 1410 episodes of
      recurrent seizures, 32% had one, 15% had two, and 7% had three or more recurrent
      seizures after a first FS; 7% had a complex seizure. The hazard of recurrent
      seizures was highest between the ages of 12 and 24 months. After a first and a
      second recurrence, the risk of further FSs was two and two and one-half times
      higher, respectively. A history of febrile or unprovoked seizures in a first
      degree family member and a relatively low temperature at the time of the first
      seizure were also associated with an increased risk of subsequent recurrences.
      Young age at onset (< 12 months), a family history of unprovoked seizures, and a
      partial initial FS were all associated with an increased risk of complex
      seizures. A higher recurrence rate in clinic-based studies compared with
      population-based studies could not be explained by a difference in the presence
      of the risk factors studied. Thus other factors must influence seizure recurrence
      after an initial FS.

PMID- 8151473
TI  - Antibiotic therapy in febrile children: "best-laid schemes".

PMID- 8151474
TI  - Evolving concepts in the evaluation of the child with a urinary tract infection.

PMID- 8151475
TI  - Use of irradiated lymphocytes from immune donors for treatment of disseminated
      varicella.
AB  - Four children with acute lymphocytic leukemia who had disseminated varicella were
      treated with infusions of apheresed, irradiated lymphocytes from healthy donors
      who had recently recovered from infection with varicella-zoster virus. Each
      patient had cessation of new lesion formation and umbilication of old lesions
      within 24 hours of the first lymphocyte transfusion. There were no side effects
      attributable to the infusions. A controlled trial of infusions of irradiated
      lymphocytes should be considered for treatment of disseminated infection with
      varicella-zoster virus in immunocompromised hosts.

PMID- 8151476
TI  - Development of atopic asthma in infants with pulmonary congestion caused by
      congenital heart disease.
AB  - We studied the effects of pulmonary congestion on the development of atopic
      asthma in 31 infants with congenital heart disease. Respiratory distress did not
      resolve after surgery in seven patients, six of whom had a family history of
      allergy. Pulmonary congestion in infancy may increase the risk of atopic asthma
      in genetically predisposed children.

PMID- 8151477
TI  - Effect of thyroid hormone treatment on thyromegaly in children and adolescents
      with Hashimoto disease.
AB  - The effect of thyroid hormone treatment on thyromegaly was evaluated in 69
      patients < or = 18 years of age with goitrous Hashimoto disease. Changes in
      goiter size were related to pretreatment thyroid function (serum thyroxine and
      thyrotropin concentrations). We found that only hypothyroid patients had a clear
      diminution of their thyromegaly when given thyroid hormone.

PMID- 8151478
TI  - Symmetric hypoplasia of the temporal cerebral lobes in an infant with glutaric
      aciduria type II (multiple acyl-coenzyme A dehydrogenase deficiency).
AB  - Symmetric hypoplasia of the temporal cerebral lobes was demonstrated by magnetic
      resonance imaging of the brain in a macrocephalic male patient with glutaric
      aciduria type II within the first week of life. Psychomotor development was
      normal until the age of 11 months, when the patient died of sudden cardiac
      arrest. Autopsy revealed symmetric hypoplasia of the temporal cerebral lobes with
      loss of axons and hypomyelination in the temporal medullary layers.

PMID- 8151479
TI  - Use of high-fat formula for premature infants with bronchopulmonary dysplasia:
      metabolic, pulmonary, and nutritional studies.
AB  - The use of dietary fat in preference to carbohydrate offers the theoretic
      advantage of diminishing carbon dioxide production and thus the respiratory
      quotient, which may be beneficial for babies with chronic lung disease. Ten
      premature infants (birth weight (mean +/- SEM), 1.13 +/- 0.12 kg; postnatal age,
      9 +/- 1 weeks) with bronchopulmonary dysplasia were alternately fed a high-fat
      and a high-carbohydrate formula each for 1 week, in randomized order. Lower rates
      of carbon dioxide production (6.6 +/- 0.3 versus 7.4 +/- 0.4 ml/kg per minute; p
      < 0.05), and consequently lower respiratory quotients (0.80 +/- 0.02 versus 0.94
      +/- 0.01 ml/kg per minute; p < 0.005), were observed during the administration of
      the high-fat formula. There were no significant differences in results of
      pulmonary function tests with the use of either formula. Both formulas were
      equally well tolerated and able to promote adequate growth and normal biochemical
      profiles. However, weight gain was significantly greater with the administration
      of the high-carbohydrate formula, possibly because of an increase in the
      accretion of body fat. We conclude that the short-term use of high-fat formula
      for infants with bronchopulmonary dysplasia decreases carbon dioxide production
      while maintaining adequate growth and nutritional status.

PMID- 8151480
TI  - Extensive intraalveolar pulmonary hemorrhage in infants dying after surfactant
      therapy.
AB  - To assess the possible relationship between exogenous surfactant therapy and
      pulmonary hemorrhage in premature infants, we compared autopsy findings in 15
      infants treated with exogenous surfactant and in 29 who died before the
      introduction of surfactant therapy. Infants who met the following criteria were
      included: birth weight 501 to 1500 gm, survival 4 hours to 7 days, and no
      congenital anomalies. Average birth weight, gestational age, and age at death
      were equivalent for the two groups. High rates of pulmonary hemorrhage were
      present in both groups (treated 80% vs untreated 83%). The untreated group had
      higher incidences of interstitial hemorrhage and lung hematomas and significantly
      more large interstitial hemorrhages: 31% untreated versus 0% treated (p < 0.05).
      The overall rate of intraalveolar hemorrhage was similar in the two groups, but
      surfactant-treated infants were more likely to have extensive intraalveolar
      hemorrhage: 53% versus 14% (p < 0.05). Most surfactant-treated infants who
      survived more than 24 hours had extensive intraalveolar hemorrhage (8/9).
      Patients who had extensive intraalveolar hemorrhage, with or without prior
      surfactant therapy, frequently had clinically significant pulmonary hemorrhage
      (7/12). These findings indicate that infants who die after surfactant therapy
      have higher rates of a specific type of pulmonary hemorrhage--extensive
      intraalveolar hemorrhage.

PMID- 8151481
TI  - Blood pressure ranges in premature infants. I. The first hours of life.
AB  - We studied blood pressure in the first hours of life in a cohort of 1105 preterm
      infants weighing 501 to 2000 gm; these infants represented 83% of all births at
      these weights that resulted in admission to three intensive care nurseries during
      a 34-month period between 1984 and 1987. To assess the effects of specific risk
      factors, we identified 244 healthy infants, 164 infants who received mechanical
      ventilation but had no other conditions, 47 infants whose only risk factor was
      the presence of hypertension or preeclampsia in the mother, and 86 infants with
      depressed Apgar scores regardless of the presence of the other conditions. We
      documented each infant's minimum and maximum systolic (Smin, Smax) and diastolic
      (Dmin, Dmax) pressures during the first 3 to 6 hours of life. In the healthy
      group, Smin was 47 mmHg; Smax, 59 mmHg; Dmin, 24 mmHg; and Dmax, 35 mmHg. In the
      ventilation group, Smin was 41 mmHg; Smax, 57 mmHg; Dmin, 22 mmHg; and Dmax, 35
      mmHg. The Smin and Dmin values were both significantly lower in infants who
      received mechanical ventilation than in healthy infants (p < 0.01). In the
      maternal hypertension group, Smin was 49 mmHg; Smax, 59 mmHg; Dmin, 25 mmHg; and
      Dmax, 34 mmHg. Only the Smin value was significantly higher than in healthy
      infants. In the group with low Apgar scores, Smin was 33 mmHg; Smax, 51 mmHg;
      Dmin, 19 Hg; and Dmax, 34 mmHg. Thus all these values were significantly lower
      than in all the other groups (p < 0.05). Of infants with low Apgar scores, 20% to
      50% had values below the 5th percentile for healthy infants. Birth weight and
      gestational age correlated with blood pressure limits only in the infants with
      low Apgar scores. We conclude that in healthy premature infants the limits of
      systolic and diastolic blood pressure are independent of birth weight and
      gestational age. Infants with low Apgar scores tend to have lower pressures, and
      infants whose mothers have hypertension have higher pressures than infants in the
      healthy cohort.

PMID- 8151482
TI  - Persistent pulmonary hypertension in newborn infants with cogenital myotonic
      dystrophy.
AB  - We describe two infants with congenital myotonic dystrophy that was complicated
      by persistent pulmonary hypertension. Both infants died of respiratory
      insufficiency that was unresponsive to ventilatory and pharmacologic support. One
      of the two infants was supported with extracorporeal membrane oxygenation before
      the diagnosis of congenital myotonic dystrophy was made.

PMID- 8151483
TI  - Early-onset respiratory failure caused by severe congenital neuromuscular
      disease.
AB  - Two unrelated infants with low Apgar scores, pneumothoraces, and severe pulmonary
      hypertension were treated with extracorporeal membrane oxygenation while
      receiving chemical sedation and neuromuscular paralysis. After decannulation from
      extracorporeal membrane oxygenation, hypotonia and hypoventilation persisted.
      Neurologic evaluation confirmed that both infants had a congenital myopathy.

PMID- 8151484
TI  - Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis.
AB  - Pseudoporphyria, a cutaneous disorder characterized by skin fragility,
      vesiculation, and scarring, has been reported as a side effect of naproxen
      therapy in children with juvenile rheumatoid arthritis (JRA). We report the
      results of a 6-month prospective study to determine the prevalence of
      pseudoporphyria in our JRA population. All the patients with pseudoporphyria had
      received naproxen for > or = 4 weeks at the time of the study. Of the patients
      treated with naproxen, 12% (9/74) developed this complication. No patient had
      significant elevation of free erythrocyte protoporphyrin, excluding the diagnosis
      of true erythropoietic protoporphyria. We conclude that pseudoporphyria is a
      common side effect of naproxen therapy in children with JRA, even in geographic
      areas without high sun exposure. Because of the risk of facial scarring with
      pseudoporphyria, physicians and parents of children with JRA should be aware of
      this complication.

PMID- 8151485
TI  - Use of lidocaine-prilocaine cream for vaccination pain in infants.
AB  - PURPOSE: To determine whether use of lidocaine-prilocaine 5% cream (EMLA)
      decreases pain associated with diphtheria-pertussis-tetanus (DPT) vaccination in
      infants. METHODS: Randomize, double-blind, controlled trial in outpatient
      pediatric practice, Toronto, Ontario, Canada. Before vaccination, parents applied
      2.5 gm of EMLA or placebo to the infant's leg and covered it with an occlusive
      dressing for at least 60 minutes. The infant received a 0.5 ml intramuscular
      injection of DPT at 2 degree to 8 degree C with a 1.6 cm 25-gauge needle; the
      infant was videotaped. The Modified Behavioral Pain Scale (MBPS) was used to
      assess baseline and postvaccination pain scores. Latency and duration of infant
      cry were also measured. RESULTS: A total of 49 evaluable infants received EMLA,
      and 47 infants received placebo. There were no significant differences in
      demographic data; mean age was 5 months; and 50% of the subjects were male. The
      median difference in pre-vaccination and postvaccination MBPS scores was lower
      for EMLA than for placebo (p = 0.001). The latency to the first cry was longer
      for subjects who were treated with EMLA (p = 0.0004)), but the total crying time
      was shorter (10.3 seconds vs 25.2 seconds; p = 0.027). Of the study group, 90%
      (45/50) of subjects treated with EMLA and 12% (6/49) of subjects treated with
      placebo had local skin reactions (p < 0.0001), mainly skin blanching.
      CONCLUSIONS: Pretreatment with EMLA decreases infant pain from DPT vaccinations.
      Application of these data is limited to healthy infants receiving DPT
      vaccinations.

PMID- 8151486
TI  - Concentrations of procaine and aqueous penicillin in the cerebrospinal fluid of
      infants treated for congenital syphilis.
AB  - Penicillin concentrations in cerebrospinal fluid (CSF) were measured at various
      hours and days of treatment in 163 infants undergoing therapy for congenital
      syphilis. The CSF levels were compared for three treatment regimens. Aqueous
      penicillin G (A-PEN), 100,000 U/kg per day, was used in 23 infant, and a dosage
      of 200,000 U/kg per day was used in 40 patients; procaine penicillin G (P-PEN),
      50,000 U/kg per day, was used in 100 children. Mean CSF penicillin levels were
      0.416, 0.493, and 0.077 microgram/ml, respectively, in the three treatment
      groups. The mean CSF penicillin concentration among the 63 infants treated with
      either of the A-PEN regimens (0.465 microgram/ml) was significantly greater than
      the mean concentration (0.077 microgram/ml) among those treated with P-PEN (p <
      0.001). Among those who received A-PEN, the difference in dosage was not
      associated with a significant difference in mean CSF penicillin concentration (p
      = 0.68). All the specimens obtained from patients who received A-PEN, but only
      82% of those from patients who received P-PEN, had treponemicidal concentrations
      (> or = 0.018 microgram/ml). However, 33.3% (9/27) of specimens from infants who
      received P-PEN, tested between 18 and 24 hours after a dose, had CSF penicillin
      concentrations < 0.018 microgram/ml. These data suggest that administration of A
      PEN may be the preferred therapy if CSF levels > 0.018 microgram/ml are desired,
      especially for infants with severe disease or congenital neurosyphilis.

PMID- 8151487
TI  - Interstitial lung disease in lysinuric protein intolerance.

PMID- 8151488
TI  - Diagnosis of Niemann-Pick disease type C.

PMID- 8151489
TI  - Possible effect of D-penicillamine on the physiologic action of inhaled nitric
      oxide in neonates.

PMID- 8151490
TI  - Sepsis terminology in pediatrics.

PMID- 8151491
TI  - Equations for calculation of theophylline dose.

PMID- 8151492
TI  - Preschoolers' evaluations of physical disabilities: a consideration of attitudes
      and behavior.
AB  - Assessed preschoolers' attitudes about orthopedically handicapped individuals
      with a standard picture-ranking task. Children generally exhibited a functionally
      related preference for nonhandicapped individuals. One month later, the same
      children were videotaped reading and playing basketball with a female adult in a
      wheelchair or in a chair. Preferences for a normal play partner during reading or
      during sports on the picture-ranking task did not relate to frequency of social
      interactions. Liking preference for a normal play partner, in conjunction with
      gender of the child, predicted frequency of social interactions during both tasks
      regardless of examiner's handicap status. Thus, the adoption of a negative bias
      had a general influence; any potential behavioral biases, as reflective of
      preference biases, were undifferentiated and unfocused in these preschoolers.

PMID- 8151493
TI  - The development of a Q-sort behavioral rating procedure for pediatric HIV
      patients.
AB  - Developed a Q-sort procedure to assess social, emotional, and motivational
      behavior associated with central nervous system disease among 180 HIV-infected
      pediatric patients. These ratings were factor analyzed and scales were derived
      based on the factor structure. Younger (M age = 1.03 years) patients with HIV
      associated encephalopathy were rated as more apathetic and nonsocial in their
      behavior than nonencephalopathic younger patients. Older (M age = 7.8 years)
      encephalopathic patients had significantly higher scores on scales measuring
      depression, autism, and irritability compared to nonencephalopathic patients from
      this age group. A subgroup (26 patients) showed a significant decrease in these
      elevated scores after a 6-month course of AZT.

PMID- 8151494
TI  - Preadolescents' perceptions of AIDS before and after Earvin Magic Johnson's
      announcement.
AB  - Compared sixth graders' AIDS concerns before and after Magic Johnson announced
      that he tested HIV-positive. Examined perceptions of self/other vulnerability
      (optimistic bias) using questionnaires (Study A) and interviews (Study B). Also
      examined AIDS worries mentioned in open-ended interviews (Study C). Studies A and
      B revealed a substantial degree of optimistic bias. Study C showed that AIDS is a
      prime concern of school-age students, mentioned under free or context-cued
      conditions by about 50%. There was little detectable effect of the publicity; the
      sole before--after difference in three studies was one increase in self- and
      other-vulnerability to AIDS--an increase attributable, with marginal
      significance, only to girls. Discussed implications for health promotion and
      differences between assessment approaches.

PMID- 8151495
TI  - Adaptive behavior of children with symptomatic HIV infection before and after
      zidovudine therapy.
AB  - Assessed longitudinally the effects of HIV infection and zidovudine on the
      adaptive behavior of 25 children with symptomatic disease (M age = 5.3 years;
      range = 1-12; 52% classified as encephalopathic) by parent report using the
      Vineland Adaptive Behavior Scales. Patients also were evaluated with an age
      appropriate intelligence test and Q-sort Behavioral Rating Scale. Before
      treatment, encephalopathic children exhibited greater impairments in adaptive
      behavior than those without encephalopathy. After 6 months of zidovudine, all
      behavioral domains (communication, daily living, socialization) except for motor
      skills showed overall significant improvement. Children with or without
      encephalopathy showed a similar degree of change. Improvements in adaptive
      behavior correlated with increases in cognitive ability and decreases in severity
      of aberrant social-emotional behavior.

PMID- 8151496
TI  - Biological and environmental correlates of developmental outcome of prematurely
      born infants in early adolescence.
AB  - Examined the role of biological factors (birth weight and perinatal medical
      complications) and psychosocial factors (maternal attitudes, paternal
      involvement, mother's personal state, marital adjustment, family relations, and
      socioeconomic status) in predicting long-term outcome of 90 Israeli adolescents
      born prematurely at very low birth weight (VLBW). As compared with 90 adolescents
      born full-term at normal birth weight (NBW), the VLBW children scored lower on
      all measures except reading comprehension. IQ, visual-motor coordination, and
      hyperactive behavior were predicted by both biological and psychosocial
      variables, visual memory by biological variables, and reading comprehension by
      psychosocial variables. The findings support chiefly the main effects model of
      developmental psychopathology (i.e., biological and psychosocial variables are
      additive in predicting outcomes), but also the interactional model (e.g., SES was
      influential in predicting visual-motor coordination and hyperactive behavior in
      the VLBW group but not in the NBW group).

PMID- 8151497
TI  - Previous injuries and behavior problems predict children's injuries.
AB  - Investigated factors related to unintentional injuries in 50 children from summer
      day camps for economically underprivileged youth. Data were collected on parent
      reports of children's previous medically treated injuries, Eyberg Child Behavior
      Inventory (ECBI) scores, and the day camp's incident reports of injuries. One
      year later, parents completed a second questionnaire about medically and home
      treated injuries. Multiple linear regression indicated that previous medically
      treated injury, ECBI opposition score, and injury at camp accounted for 50% of
      the variance of medically treated injuries in the year after camp. Previous
      medically treated injury accounted for 21% of the variance in frequent home
      treated injuries during the year after camp. Children who have behavior problems
      may behave in ways that predispose them to common injuries. Conceptualizing
      injury as a behavioral process suggests behavior change strategies to reduce
      injury risk and ways to target children for injury prevention efforts.

PMID- 8151498
TI  - Beliefs about illness causality among preschoolers with cancer: evidence against
      immanent justice.
AB  - Evaluated whether preschoolers with cancer are more or less likely than their
      healthy counterparts to consider illness a form of punishment for misdeeds
      (immanent justice). It was found that a sample of preschoolers with cancer (n =
      17) rejected immanent justice as a general cause of illness, both in themselves
      and in others, just as frequently as healthy controls (n = 17). Both groups also
      rejected immanent justice in cases where misbehavior was prolonged. Children with
      cancer demonstrated a view of illness causality based on greater differentiation
      between themselves and other people, in that they were more likely than healthy
      controls to accept immanent justice as a cause of illness in themselves but not
      others, and vice versa. Finally, nearly all of the children with cancer who
      accepted immanent justice as a general cause of illness in themselves also
      attributed their cancer specifically to immanent justice.

PMID- 8151499
TI  - Consensus, self-other agreement, and accuracy in personality judgment: an
      introduction.
AB  - Consensus in personality judgment refers to the agreement with which two people
      (or more) can describe the personality of another; self-other agreement refers to
      the similarity between personality descriptions by the self and by others; and
      accuracy refers to the degree to which personality descriptions capture real
      attributes of the persons described. After years of focusing on other subjects,
      researchers recently have renewed their interest in these three topics. Current
      empirical research is philosophically diverse and includes studies incorporating
      pragmatic, constructivist, and realist approaches. Other research is resolving
      long-standing methodological problems and providing new analytic techniques for
      the study of consensus, self-other agreement, and accuracy. This special issue
      includes articles exemplifying all of these research approaches and documents
      that a new wave of research on consensus, self-other agreement, and accuracy in
      personality judgment now comprises a burgeoning field that has finally come of
      age.

PMID- 8151500
TI  - Determinants of interjudge agreement on personality traits: the big five domains,
      observability, evaluativeness, and the unique perspective of the self.
AB  - We examined several determinants of interjudge agreement on personality traits.
      The findings, which were cross-validated in two samples, suggest that agreement
      is a function of four factors: which Big Five content domain the trait
      represents, how observable relevant behaviors are, how evaluative the trait is,
      and whether the self is one of the judges. Agreement was highest for traits
      related to Extraversion and lowest for traits related to Agreeableness. More
      observable and less evaluative traits elicited higher interjudge agreement. On
      average, self-peer agreement was lower than peer-peer agreement. However, this
      effect was limited to evaluative traits; for neutral traits, self-peer agreement
      was as high as peer-peer agreement. These findings suggest that self- and peer
      perception proceed through similar processes for neutral traits but not for
      highly evaluative traits, raising the possibility that self-perceptions become
      distorted when the trait is affectively charged.

PMID- 8151501
TI  - Childhood antecedents of young-adult judgability.
AB  - Research has recently demonstrated that the personalities of some individuals are
      more accurately judged than others, and that these "judgable" persons possess a
      coherent and identifiable personality structure (Colvin, 1993). In this article,
      four indices of judgability, based on personality descriptions provided by
      trained examiners, friends, and self, were derived when subjects were 18 and 23
      years of age. A reliable composite of the four indices was related to adolescent
      and childhood personality ratings. The results reveal (a) rank-order stability of
      judgability from age 18 to age 23, (b) that adolescent ego resiliency predicts
      judgability in early adulthood, and (c) that adolescent ego resiliency mediates
      the relationship between childhood personality and young-adult judgability, but
      only for men. Observed gender differences and similarities are discussed.
      Overall, the convergence between the results from this study and previous
      research provides evidence for the construct validity of judgability.

PMID- 8151502
TI  - Accuracy in interpersonal expectations: a reflection-construction analysis of
      current and classic research.
AB  - Research and theory on interpersonal expectations have been dominated by a strong
      social constructivist perspective arguing that expectancies are often inaccurate
      and a major force in the creation of social reality. The reflection-construction
      model is an attempt to examine these strong claims conceptually and empirically.
      This model assumes that social perception includes both constructivist phenomena
      and accuracy. When this model is used as a framework for interpreting research on
      teacher expectations and on the role of stereotypes in person perception, it
      shows that interpersonal expectancies are often accurate, and usually lead only
      to relatively small biases and self-fulfilling prophecies. The model also is used
      to interpret research on expectancies that has provided some of the foundations
      for the strong constructivist perspective. This reflection-construction analysis
      shows that even those studies strongly suggest that people's expectations
      generally will be highly accurate.

PMID- 8151503
TI  - Suppression and repression in discrepant self-other ratings: relations with
      thought control and cardiovascular reactivity.
AB  - Individual differences in self-other disagreement may tap phenomena that have
      been notoriously difficult to assess. For example, subjects who believe they
      possess a trait while their acquaintances disagree may be exhibiting suppression.
      Further, subjects who deny a trait while acquaintances believe it is present may
      be displaying repression. In the first study, both subjects and their closest
      friends rated the subject's hostility level. Suppressors and repressors were
      expected to exhibit enhanced thought control, and indeed these individuals were
      more able not to think about white bears when instructed to do so than
      individuals for whom there was high hostility agreement. However, this was also
      true for those with low hostility agreement. Only suppressors demonstrated blood
      pressure hyperreactivity to a hostility-provoking task as expected; this finding
      was replicated in a second study employing a different, multi-item measure of
      hostility, as well as a marker of low Agreeableness.

PMID- 8151504
TI  - Parent and teacher ratings in the assessment and prediction of antisocial and
      delinquent behaviors.
AB  - Subjects consisted of a sample of two cohorts of approximately 100 boys each
      whose behaviors were rated by their parents and teachers. Criterion variables
      included antisocial behavior, based on parent, child, teacher, and interviewer
      reports, and delinquency, based on parent and child reports in addition to
      cumulative arrest data taken from juvenile court records. The data suggest that
      mothers are focused on the daily, irritating behaviors of their sons. Teachers,
      on the other hand, appear to focus on a relatively small number of items (e.g.,
      child physically attacks others, associates with deviant peers), and thereby
      provide ratings that are better predictors of delinquency and arrest. When the
      mothers' ratings were constrained to include only items that were salient for
      teachers, their predictive validity coefficients approached the magnitude of the
      teacher coefficients.

PMID- 8151505
TI  - Unraveling the web of personality judgments: the influence of social networks on
      personality assessment.
AB  - Contemporary assessment models have focused on the degree to which self- and
      other reports of personality description agree in an effort to define consensus
      and agreement about personality attributes. In general, we believe that analyses
      of this type of data have been limited in that they tend to focus on both simple
      models (usually dyad-based) and simple aggregations of data (usually correlations
      between self- and other ratings). In addition, the behaviors used as stimuli in
      experimental settings lack the richness of behaviors in natural social settings.
      Here, we present some ideas from social network models in an effort to influence
      broader conceptualizations of agreement and consensus in assessment. Social
      network models provide a more complete description of interpersonal behavior
      beyond the dyadic level in both laboratory and natural settings. After defining
      some basic social network concepts, we go on to suggest the applicability of
      these concepts to personality assessment and, more specifically, to how these
      models might be used to study self-other agreement and consensus about
      personality judgments. Empirical data are used to illustrate social network
      concepts in the domain of personality assessment.

PMID- 8151506
TI  - Analyzing consensus in personality judgments: a variance components approach.
AB  - Although peer raters of personality traits do tend to agree, the strength of
      their consensus is often modest. This article focuses on methods for analyzing
      determinants of consensus. Variance components methods adapted from
      generalizability theory have some untapped potential for understanding gradations
      in consensus. The methods allow explicit analysis of how social categories of
      targets might affect judgments of raters from the same or different social
      categories. Limitations of the variance components approach are also discussed.
      The methods are illustrated with artificial data.

PMID- 8151507
TI  - Hodgkin's disease: impact on childbearing.
AB  - Although Hodgkin's disease is considered one of the "curable" cancers, the high
      cure rates associated with this disease are not accomplished without risk of
      potentially severe, immediate, and late side effects. Because the predominant
      histologic subtype of Hodgkin's disease found in the United States generally
      affects the 15- to 25-year-old age group, the disease, its treatment, and the
      side effects of treatment will affect many women of childbearing age. The
      treatment and its effects on the patient and offspring, including posttreatment
      fertility, are key issues for perinatal nurses.

PMID- 8151508
TI  - Clinical issues and therapeutic interventions in the care of pregnant women
      infected with the human immunodeficiency virus.
AB  - As the incidence of human immunodeficiency virus (HIV) infection increases in
      women of reproductive age in the United States, clinical issues and therapeutic
      interventions specifically addressing the needs of HIV-positive pregnant women
      will continue to evolve and be incorporated into their obstetric care. This
      article provides perinatal nurse clinicians with an overview to the epidemiology
      and clinical manifestations of HIV infection in pregnant women, as well as the
      therapeutic modalities and psychosocial components included in their plan of
      care. Data regarding perinatal transmission rates and maternal factors possibly
      facilitating vertical transmission are also presented.

PMID- 8151509
TI  - Breast cancer and pregnancy: implications for perinatal care and fetal outcomes.
AB  - The diagnosis of breast cancer has a profound impact on women and their families.
      Although relatively uncommon, breast cancer associated with pregnancy is gaining
      attention as more women choose to delay pregnancy. The perinatal nurse must
      combine a knowledge of breast cancer and its treatment with an understanding of
      how this treatment will influence current and future pregnancies. Of critical
      importance are the roles of educator and patient advocate. This clinical review
      will discuss the natural history of breast cancer associated with pregnancy, its
      diagnosis and treatment, and the nursing implications for maternal and fetal
      care.

PMID- 8151510
TI  - Characterizations and psychoneuroimmunologic implications of secretory
      immunoglobulin A and cortisol in preterm and term breast milk.
AB  - This article combines data from two separate investigations. One study examined
      relationships between psychosocial factors and preterm milk immune variables. The
      other examined relationships between psychosocial and breastfeeding satisfaction
      factors and perceived milk sufficiency in term mothers. Milk samples were
      collected on the fifth postpartum day and frozen. Both studies collected data on
      anxiety, but other psychosocial variables differed. Mood states and social
      support were studied in preterm mothers, while breastfeeding satisfaction, milk
      maturation, and infant suckling characteristics were studied in term mothers.
      Milk samples were assayed for secretory immunoglobulin A (sIgA) and cortisol.
      sIgA and cortisol levels were higher in the milk from preterm mothers and were
      inversely related to each other in both preterm and term milk. In preterm
      mothers, anger and vigor were positively correlated with higher milk sIgA. The
      findings suggest that cortisol is present in milk and may potentially influence
      the secretion of milk sIgA. The relationships that were found when comparing
      psychosocial, dyadic, and stress factors with milk sIgA and cortisol are
      provocative and suggest new paradigms for studying lactation.

PMID- 8151511
TI  - At risk for infection: the very-low-birth-weight infant.
AB  - The very-low-birth-weight (VLBW) infant is at high risk for developing infection
      during the antenatal, prenatal, and postnatal periods. The six major predisposing
      factors are perinatal infections, an immature immune system, decreased natural
      defenses, disease states and disorders leading to infection, side effects of
      medication, and prolonged hospitalization and iatrogenic complications of
      lifesaving therapies. Quality nursing care plays a crucial role in recognizing
      signs and symptoms of sepsis and facilitating a timely diagnostic evaluation.
      Prevention, prompt diagnosis, and treatment will reduce the high morbidity and
      mortality rates associated with sepsis in the VLBW infant.

PMID- 8151512
TI  - Gene therapy techniques in the treatment of adenosine deaminase--deficiency
      severe combined immune deficiency syndrome.
AB  - Gene therapy is an innovative technique utilized in the treatment of a primary
      immunodeficiency known as severe combined immune deficiency syndrome (SCIDS). The
      first human trials of gene therapy for SCIDS were conducted in 1990, by
      attempting to insert the gene for adenosine deaminase into peripheral white blood
      cells to treat children with adenosine deaminase (ADA)-deficiency SCIDS.
      Recently, three infants with ADA-deficiency SCIDS received gene therapy with
      genetically manipulated hematopoietic stem cells. This clinical update reviews
      basic immunology function and malfunction, describes gene therapy, and
      specifically highlights hematopoietic stem cell gene therapy treatment for ADA
      deficiency SCIDS.

PMID- 8151513
TI  - Management of infants born to women infected with the human immunodeficiency
      virus.
AB  - The numbers of women and children infected with the human immunodeficiency virus
      (HIV) in the United States are growing rapidly. As these numbers increase, we can
      expect a strong impact on our health care system and our society as a whole.
      Research in the area of perinatal HIV is ongoing of critical importance.
      Clinicians and hospital staff (as well as our communities) must be prepared to
      care for an ever growing number of newborns who are at risk for HIV infection.
      This article provides a review of the recent literature regarding perinatal HIV
      as well as a summary of the medical and psychosocial management of infants who
      are at risk for perinatally acquired HIV.

PMID- 8151514
TI  - The reality worlds of retirees: an Israeli case-control study.
AB  - The conceptual point of departure of this study was Cantril's "patterns of human
      concerns" as reflecting reality worlds. Subjects were 805 "on-time" retirees and
      260 kibbutz members (who do not retire) interviewed at three points in time. We
      asked two questions: Can modal themes in this map of concerns be identified as
      characteristic of an Israeli cohort of the young elderly? Do gender, class, and
      retiree/kibbutz status lead to meaningful differences in mapping the world? A
      quite common modal pattern of concerns was found in the retiree sample, with a
      central focus on family and interpersonal relations. Commonalities between the
      different sociocultural groups seemed more striking than the differences.

PMID- 8151515
TI  - Traditional ideology, stress, and psychotherapy use.
AB  - I examined the relationship of traditional ideology, a characterological and
      cultural variable, and life stress and symptoms of depression to an openness to
      the use of psychotherapy. American college students (N = 150) completed several
      questionnaires; the results showed that despite higher levels of symptoms of
      depression among traditionals, a strong negative relationship existed between
      traditional ideology and attitudes toward and use of psychotherapy. Stressful
      life events, symptoms of depression, social desirability scores, and religious
      behaviour were unrelated to attitudes toward and use of psychotherapy.

PMID- 8151516
TI  - Gender differences in achievement motive: a facet analysis of Hungarian samples.
AB  - We devised an achievement motive questionnaire (Elizur 1979, 1986; Shye 1978a)
      based on a facet definition of achievement motive. We then administered it to 165
      women and 362 men employed by a large industrial corporation in Hungary in order
      to examine achievement motivation. Although we found significant differences in
      the frequency of responses to the achievement motive items, the basic structure
      of the achievement motive domain was similar for women and men. We detected no
      special tendency for women to score higher than men on affective responses. These
      results support the view that gender differences in achievement motive are rooted
      in socialization processes rather than in basic differences between women and
      men.

PMID- 8151517
TI  - The functions of pen pals for adolescents.
AB  - We questioned adolescents in Israel who wished to have a pen pal concerning their
      motives and their reasons for wanting such a relationship. Results showed that
      pen pal correspondence was more frequently sought during the earlier years of
      adolescence and particularly among girls. Adolescents' motives and reasons for
      wanting a pen pal suggested that such a correspondence may serve the growing need
      for a close and intimate friend as well as a search for an imaginary companion.

PMID- 8151518
TI  - Middle-ear development. IV. Umbo motion in neonatal mice.
AB  - Laser interferometry was used to measure umbo velocity in the developing BALB/c
      mouse middle ear at 133 pure-tone frequencies between 2.0 kHz and 40.0 kHz, all
      at a constant 100 dB sound pressure level. Umbo velocities increased with age
      across the entire frequency range, and reached adult-like levels by about 19 days
      between 2.0 and 22.0 kHz. Velocities at 28.0 and 34.0 kHz took 27 and 52 days
      respectively to reach adult-like levels. A simple middle-ear model utilizing
      compliance, resistance, and inertia elements matched the general trends of our
      velocity results and provided an indication of the anatomical basis for the
      growth in umbo velocity. The model suggested that velocity development at the
      lowest frequencies may be attributed to increases in tympanic membrane
      compliance. The model also indicated that both the frictional resistance of the
      middle ear and the inertia of the tympanic membrane and ossicles decreased during
      the growth period. At frequencies below 20.0 kHz, age-related increases in umbo
      velocity coincided with improvements in N1 thresholds recorded from the round
      window and evoked potential thresholds obtained from the cochlear nucleus. These
      results indicated that the functional development of the middle-ear plays a major
      role in the development of hearing in the mouse.

PMID- 8151519
TI  - Identification of vertebrate volatiles stimulating olfactory receptors on tarsus
      I of the tick Amblyomma variegatum Fabricius (Ixodidae). I. Receptors within the
      Haller's organ capsule.
AB  - Gas chromatography-coupled electrophysiological recordings (GC-EL) from olfactory
      sensilla within the capsule of Haller's organ of the tick Amblyomma variegatum
      indicate the presence of a number of stimulants in rabbit and bovine odours, and
      in steer skin wash. Some of these stimulants were fully identified by gas
      chromatography-mass spectrometry analysis and by matching electrophysiological
      activity of synthetic analogues as: 1) hexanal, 2-heptenal, nonanal, furfural,
      benzaldehyde, and 2-hydroxybenzaldehyde (in all extracts); 2) heptanal, 2-, 3-,
      and 4-methylbenzaldehyde, and gamma-valerolactone (only in bovine and rabbit
      odour). Careful examination of the electrophysiological responses permit
      characterization of 6 receptor types: 1) a benzaldehyde receptor, 2) a 2
      hydroxybenzaldehyde receptor, 3) three types of receptors responding differently
      to aliphatic aldehydes, and 4) a lactone receptor.

PMID- 8151520
TI  - Critical parameters of the spike trains in a cell assembly: coding of turn
      direction by the giant interneurons of the cockroach.
AB  - Cockroaches (Periplaneta americana) respond to air displacement produced by an
      approaching predator by turning and running away. A set of 4 bilateral pairs of
      ventral giant interneurons is important in determining turn direction. Wind from
      a given side is known to produce more spikes, an earlier onset of the spike
      trains, and different fine temporal patterning, in the ipsilateral vs the
      contralateral set of these interneurons. Here we investigate which of these spike
      train parameters the cockroach actually uses to determine the direction it will
      turn. We delivered controlled wind puffs from the right front, together with
      intracellular injection of spike trains in a left ventral giant interneuron,
      under conditions where the animal could make normally directed turning movements
      of the legs and body. In trials where our stimuli caused the left side to give
      both the first spike and more total spikes than the right, but where our injected
      spike train included none of the normal fine temporal patterning, 92% of the
      evoked turns were to the right-opposite of normal (Figs. 4-6). In trials where
      the left side gave the first spike, but the right side gave more spikes, 100% of
      the turns were to the left--the normal direction (Figs. 8, 9). Comparable results
      were obtained when each of the left giant interneurons 1, 2 or 3 were
      electrically stimulated, and when either weak or stronger wind puffs were used.
      Stimulating a left giant interneuron electrically in the absence of a wind puff
      evoked an escape-like turn on 9% of the trials, and these were all to the right
      (Fig. 9). These results indicate that fine temporal patterning in the spike
      trains is not necessary, and information about which side gives the first spike
      is not sufficient, to determine turn direction. Rather, the key parameter appears
      to be relative numbers of action potentials in the left vs the right group of
      cells. These conclusions were supported by similar experiments in which
      extracellular stimulation of several left giant interneurons was paired with
      right wind (Figs. 11, 12).

PMID- 8151521
TI  - A putative suprachiasmatic nucleus of birds responds to visual motion.
AB  - In mammals, the suprachiasmatic nucleus (SCN) is a pacemaker regulating daily
      rhythms. In birds, two retinorecipient nuclei have been called the avian SCN, one
      in the lateral hypothalamus and the other more medial and rostral. We asked
      whether the proto-oncogene c-fos is expressed in either nucleus after light
      exposure during subjective night, but not during subjective day, as is the case
      in the SCN of mammals. Chicks raised with one eye covered by a diffuser were
      exposed to vertically moving surroundings, after the diffuser had been switched
      to the other eye. Surprisingly, we saw strong Fos label only in the lateral
      nucleus contralateral to the eye newly exposed to visual motion, but not in the
      ipsilateral nucleus nor in either medial SCN. No label was seen in animals kept
      in darkness or if the diffuser was not switched. Fos labeling did not differ
      between subjective day and night. The sensitivity to "novel" motion is also seen
      in motion-processing nuclei of the accessory optic system and pretectum; this
      suggests either that the lateral SCN is not the SCN, but part of the motion
      pathway, or that the avian SCN may by motion-sensitive during both day and night.

PMID- 8151522
TI  - Multiple effects of an identified proprioceptor upon gastric pattern generation
      in spiny lobsters.
AB  - 1. Using deafferented preparations of the stomatogastric nervous system of spiny
      lobsters (Panulirus interruptus), we stimulated the central soma of the Anterior
      Gastric Receptor neuron (AGR) and analyzed sensorimotor integration in the
      gastric central pattern generator during rhythm production. 2. Driving AGR to
      spike tonically at lower frequencies (10-20/s) accelerated the gastric rhythm,
      while higher frequencies (> or = 30/s) suppressed it. 3. Shorter spike trains in
      AGR evoked phase-dependent resetting of the gastric rhythm. Repetitive trains
      could entrain rhythms to both longer and shorter cycle periods. Some pattern
      generating effects are consistent with effects upon the lateral gastric neuron,
      an influential member of the gastric mill network. 4. AGR affected the burst
      intensity of many of the gastric neurons in specific, complex ways. Some power
      stroke motor neurons were excited because AGR activated excitatory, premotor
      interneurons (E cells). However, AGR also activated parallel, seemingly
      inhibitory inputs, whose mechanism remains unclear. Still other effects on motor
      neurons may be mediated partly by synaptic interactions within the network.

PMID- 8151523
TI  - Discharge patterns of chicken cochlear ganglion neurons following kanamycin
      induced hair cell loss and regeneration.
AB  - Hair cells in the basal, high frequency region (> 1100 Hz) of the chicken cochlea
      were destroyed with kanamycin (400 mg/kg/d x 10 d) and allowed to regenerate.
      Afterwards, single unit recordings were made from cochlear ganglion neurons at
      various times post-treatment. During the first few weeks post-treatment, only
      neurons with low characteristic frequencies (< 1100 Hz) responded to sound.
      Despite the fact that the low frequency region of the cochlea was not destroyed,
      neurons with low characteristic frequencies had elevated thresholds, abnormally
      broad U-shaped or W-shaped tuning curves and low spontaneous discharge rates. At
      2 days post-treatment, the spontaneous discharge rates of some acoustically
      unresponsive units fluctuated in a rhythmical manner. As recovery time increased,
      thresholds decreased, tuning curves narrowed and developed a symmetrical V-shape,
      spontaneous rate increased and neurons with higher characteristic frequencies
      began to respond to sound. In addition, the proportion of interspike interval
      histograms with regularly spaced peaks increased. These improvements progressed
      along a low-to-high characteristic frequency gradient. By 10-20 weeks post
      treatment, the thresholds and tuning curves of neurons with characteristic
      frequencies below 2000 Hz were within normal limits; however, the spontaneous
      discharge rates of the neurons were still significantly lower than those from
      normal animals.

PMID- 8151524
TI  - [Pattern of blood creatinine levels in 140 hypertensive patients after successful
      percutaneous transluminal angioplasty for renal artery stenosis].
AB  - Long term effects on creatinine serum level of successful percutaneous
      transluminal renal angioplasty were retrospectively studied in 140 patients. 3
      groups were distinguished: the first one (80 patients) included unilateral renal
      angioplasties, with normal contralateral kidney and renal artery; the second
      group (35 patients) included bilateral renal angioplasties; the third group (25
      patients) included solitary kidney renal artery angioplasties. In each group,
      subgroups were defined whether creatinine serum level was upper or lower than 130
      mumol/l. Renal function was considered to be improved if serum creatinine was
      reduced by 20% or more, maintained if serum creatinine variations were below 20%,
      worsened if its increase was upper than 20%. Global complication rate was 4.9% (9
      between 185 patients) of whom 1 (0.54%) needed a surgical revascularization. At
      the end of follow-up (mean between 4 and 10 months), subgroups improvement and
      stabilization rates varied between 67 and 100%, with the best scores in the
      second group (96.2 and 100%) and solitary kidney with renal insufficiency
      subgroup (77.25%).

PMID- 8151525
TI  - [Radiological aspects of vertebro-medullary hydatid cysts. Apropos of 12 cases].
AB  - Twelve cases of vertebro-spinal hydatidosis were reviewed, over nine years
      period, to specify its clinical and histological characters. This localization,
      although rare, is the most common of the bone hydatidosis (44%). The authors
      develop the imaging methods contribution in positive and differential diagnosis,
      and underline the modern methods interest (CT scan, MR imaging) notably in
      spreading assessment and medical supervision.

PMID- 8151526
TI  - [Radiological aspects of histiocytosis X].
AB  - The histiocytosis X is a tumoral affection related to the proliferation of a
      highly differentiated cell which reaches the reticulohistiocytary system. The
      radiology represents on top of the clinic and the histology, the central pillar
      of this diagnostic tripod. This retrospective study is about 14 files of patients
      collected in different departments of UHC Ibn Rochd between 1976 and 1988. In the
      14 observations, the diagnosis has been confirmed by an anatomopathologic
      examination. The disease supervenes with predominance at the young age (9 cases
      11 years). The reach of the bone is very frequent (9/14 cases) and often multiple
      (7/9 cases), the preferential localizations are at the craniofacial level (50%),
      at the level of flat bones, the girdles (25%), the femur and the tibia (25%). The
      radiologic aspect is an osteolysis in the shape of lacunae with rounded and
      outlines suited with "take-piece", sometimes polycyclic in the card of geography.
      This osteolysis has sometimes a quite characterized aspect of the disease
      especially at the level of the cranium, the maxillomandibular massive, the
      supracotyloid region and the rachis. The reach of the lun during the
      histiocytosis X is relatively frequent (4/14 cases). It is often about an
      interstitial pneumopathy that is sometimes complicated of pneumothorax. The
      standard radiologic examinations of the osseous Skeleton help in making the
      diagnosis, permitting the complete physical examination of the extension and the
      supervision of the disease. The scintigraphy is less reliable and the scanner is
      not specific. However, the scanner explores better the base of the Skull and
      certain viscers which the reach can make revise the prognosis.

PMID- 8151527
TI  - [Extensive malignant schwannoma of the sciatic nerve. Contribution of imaging
      techniques].
AB  - The authors reports a case of malignant schwannoma of sciatic nerve. Clinically,
      this tumor was manifested by a progressive tumefaction of the leg, and moderate
      pain, without functional signs. The origin of the sciatic nerve has been
      suspected by computed tomography, because its location, the vascular contacts,
      and the lesion's extension. Biopsy leads to confirm the nerve tumor, and precised
      the histologic type: malignant schwannoma. Local, regional and general extension
      did not premise treatment.

PMID- 8151528
TI  - [Progressive multifocal leukoencephalopathy localized in the thalamic grey matter
      in an AIDS-patient].
AB  - Involvement of the deep grey matter is unusual in Progressive Multifocal
      Leukoencephalopathy (PML), which is disease of the white matter. Basal ganglia
      involvement is usually secondary to extension from lesions of adjacent white
      matter and easy to recognize. We report a biopsy-proven case of PML in which
      lesions were mainly thalamic.

PMID- 8151529
TI  - [Vascular involvements in Behcet disease. Based on 40 patient records].
AB  - The authors report about 40 cases of Behcet's disease with vascular involvement,
      i.e. 32% of a 125 case series. The results were marked by the high frequency of
      venous involvement (36 cases, including 28 thrombophlebitis of the deep trunks of
      the lower limbs) and the rarity of arterial involvement (6 cases). Arterial and
      venous involvements were associated in only 2 cases. Inferior vena caval
      thrombosis was recognized in 4 cases, including 3 with associated lower limb
      thrombosis. Superior vena caval thrombosis is found in 6 cases. Superior
      cavography has allowed demonstrating thrombosis and assessing its extent, to the
      innominate veins in all cases, to the subclavian veins in 3 cases, and to the
      axillary veins in 1 case. Cases of arterial involvement include 5 cases of
      pulmonary arterial aneurysm and 1 of upper limb arteritis affecting the humeral
      and cubital arteries. It has been revealed by hemoptysis in all cases.
      Angiography has allowed establishing the diagnosis of aneurysm in 4 cases (3 with
      partial thrombosis and 1 without thrombosis). CT revealed the diagnosis of
      completely thrombosed aneurysms not opacified by angiography in another case.

PMID- 8151530
TI  - [Selective arteriography of the supra-aortic trunks by right humeral approach
      with a 4F catheter].
AB  - Three hundred and sixty seven patients were studied for cerebrovascular disease
      with intra-arterial digital subtraction. Examination were performed using a right
      transbrachial approach with a 4F catheter. Selective catheterization of the
      carotid arteries was possible in 98% for the left and 99% for the right. Image
      quality was consistently good or excellent. There was 2 neurologic complications
      and 1 local complication (hematoma) requiring surgery few weeks later. Selective
      carotid and vertebral catheterizations by the brachial route is safe, simple,
      accurate and rapid (15 mn) and can be employed in outpatients.

PMID- 8151531
TI  - [Memories of an X-ray bulb. 2: Portrait of a family. The war].

PMID- 8151532
TI  - [Radiology in the medicolegal identification of cadavers. A new technique of
      radiography of the maxilla].
AB  - After removal, the maxilla and the mandible are placed on a standard radiologic
      cassette and a X-ray is performed with a low energy beam. Different views can be
      obtained if required. These radiographic images provide a complete, permanent and
      detailed record of dental anatomy and restorations, for comparison with
      antemortem radiographies. Two examples are provided. Moreover, this technique
      enables the determination of the dental age of children.

PMID- 8151533
TI  - [Radionuclide studies in the surveillance of the renal transplant].
AB  - Since Collins et al. first reported in 1963 that ortho-iodohippurate is taken up
      by the parenchyma, much progress has been made in isotope techniques. Advances
      have been made in the performance of the gamma cameras and the associated data
      processing. A major step was the introduction of tracers for studying renal
      function. More than an imagery technique, scintigraphy is a means of exploring of
      organ function. Its non-invasiveness and the low patient irradiation allow for
      repeated use, especially for long term follow ups. It is therefore important to
      precisely define the role of scintigraphic techniques in the follow up of renal
      transplantations in coordination with other techniques including echography.

PMID- 8151534
TI  - [Imaging of the renal transplant. Radiological methods].
AB  - Ultrasound examination with morphological sonography and color flow imaging is
      now considered as the main technique for the follow-up of renal transplants.
      Morphology of the graft, and quality of perfusion can be assessed non invasively
      with this technique. Indications of IV pyelography decreased considerably in many
      centers. CT can help in characterizing intra-abdominal collections. MR will
      probably play a major role in the future allowing the graft itself, the perirenal
      space, and the intrarenal vessels to be studied by means of MR-angiography
      techniques.

PMID- 8151535
TI  - [The transplanted kidney. Role of imaging in early non-functioning grafts].
AB  - Renal failure following transplantation can be classified in two groups: initial
      non function characterized by the absence of renal function after transplantation
      and delayed secondary non function after an initial improvement. In the first
      group, the most frequent etiology is an acute tubular necrosis (30 to 50% of the
      cases) which usually heals within three weeks. Arterial thrombosis are rare but
      of very bad prognosis. In the second group, the most frequent cases are acute
      rejection, urological complications, renal artery stenosis, urinary infections
      and cyclosporine, intoxication. Diagnostic imaging, and especially the color
      Doppler flow, is very effective in obtaining diagnosis. Vascular or urological
      complications are to be confirmed by contrasted opacifications. In the absence of
      vascular or urological obstruction renal failure must be related to a renal
      parenchymal disease. This may be acute tubular necrosis, a rejection, a
      pyelonephritis or a medicinal intoxication depending on clinical symptoms, the
      time of their apparition and the results of biological examinations.

PMID- 8151536
TI  - [Acute postoperative renal insufficiency in renal transplantation. Incidence and
      risk factors].
AB  - Delayed renal function (DFG) is known to influence both the short and long-term
      outcome of transplanted kidneys. Data collected retrospectively on all 129
      cadaveric renal transplants performed between January 1991 and January 1993
      within a single center were analyzed. 42 (32.55%) cases of acute renal failure
      (ARF) occurred during the immediate postoperative period and 28 patients required
      dialysis. When compared with immediate good allograft function, DGF was
      associated with previous failed transplant (7/15 vs 35/114, p = 0.01), donor age
      (39.2 +/- 13 vs 30.1 +/- 12 years, p = 0.01), and episodes of collapsus of the
      donor (11/25 vs 31/104, p < 0.01). The graft function of the recipient was not
      correlated with the serum creatinine of the donor. There was no apparent
      relationship between the cold ischemia or the anastomosis time and the occurrence
      of DGF. One-year patient and graft survival were similar in the two groups
      (respectively for the group ARF and without ARF: 96.4% and 96.5%; 88.8% and 89%),
      but patients with DGF had higher serum creatinine values at 12 months post DGF
      (185.6 +/- 44.8 mumol/l vs 157.5 +/- 30.8 mumol/l, p = 0.06). This study suggests
      that DGF is related to the characteristics of the donor graft and is more
      frequently encountered in previously transplanted recipients.

PMID- 8151537
TI  - [The reaction of rejection. Elements of diagnosis, surveillance, therapeutic
      attitude in cases of kidney grafts].
AB  - Allograft rejection reaction must be integrated within the general framework of
      alloreactivity, i.e. involving a huge T cell repertoire with a high number of
      alloreactive precursors. This reaction is modulated by the particular
      immunological state induced by chronic renal insufficiency, haemodialysis and
      primary kidney disease. The inefficiency of current immunosuppressive drugs is
      illustrated by the tendency towards chronic rejection, involving many growth
      factors. It must be noted that allo-stimulating cells are different from target
      cells. Therapeutical armamentarium currently involves corticosteroids and
      serotherapy, but it is hoped that new immunosuppressive drugs will increase the
      efficiency of rejection crisis treatment.

PMID- 8151538
TI  - [Diagnosis and percutaneous treatment of urinary collections and obstructions].
AB  - The collections encountered around the renal transplant are mainly lymphoceles,
      more rarely hematomas, abscesses and urinomas, the frequency of which
      constituting 12% of cases. Their diagnosis is usually made by sonography; the
      percutaneous puncture is guided by US or CT in order to define its nature and
      drain the cavity. Urinary obstruction (6% of the cases) may be detected by
      sonography or scintigraphy, but percutaneous pyelography is often required to
      confirm the obstruction, to precise its level and nature, and to guide the
      percutaneous procedure. In the case of urinoma (3% of the cases), ultrasound may
      be unclear and the urinary extravasation must be then confirmed by scintigraphy,
      postinjection delayed plain or CT scan films.

PMID- 8151539
TI  - [Surgical treatment of urinary collections and obstructions in renal
      transplantation].
AB  - Collections after renal transplantation are represented by lymphoceles, hematomas
      and urinary leaks. Symptomatic lymphoceles should be treated by external puncture
      and drainage. Deeper lymphoceles and prolonged lymphorrhea must be surgically
      marsupialised, in association with epiploplasty. Acute hematoma in the area of
      transplantation requires surgical exploration and external drainage--this may
      induce a lymphorrhea. Urinary leaks and urinomas require drainage as well as an
      ureteral support. The leakage area determines whether surgery is necessary: be it
      reimplantation, psoichal bladder or nature ureter. Intraluminal urinary
      obstructions responds to conventional urologic treatment. Distal parietal
      obstructions are surgically treated in the case of failure of percutaneous
      treatment by reimplantation, psoichal bladder, native ureter, or even
      ureteroplasty or prosthesis. Stenoses extending over the entire ureter require
      surgical ureteral reconstruction. The treatment of extrinsic obstructions can be
      by ureteral drainage, uterolysis or ureteral reconstruction. In case of such
      complications, percutaneous techniques have reduced frequency and morbidity of
      open surgery.

PMID- 8151540
TI  - [Carcinoma of the native kidney in patients with renal transplantation. A French
      multicenter study].
AB  - A study was undertaken to investigate the development of carcinoma in patients'
      own kidneys after renal transplantation. Twenty carcinomas were diagnosed among
      16,755 patients grafted from 1952 to February 1993. It was possible to collect
      data for 17 detected carcinomas. These tumours developed in 17 patients, 14 male
      and 3 female, aged 31 to 64 years old. They appeared an average of 40 (range 1
      204) months after transplantation. The maintenance treatment consisted of
      cyclosporine in 15 recipients. Four patients demonstrated clinical signs. The
      other 13 carcinomas were diagnosed as an incidental finding on ultrasound (n =
      10), at autopsy (n = 1) or by examination of kidneys from nephrectomy (n = 2). In
      the patient group with incidental diagnosis, tumors were larger than 4 cm in 3
      out of the 9 cases studied; they were confined to the kidney in 5 cases and lymph
      node invasion or renal vein involvement were noted in 1 case. Distant metastases
      were present in 3 symptomatic patients and in 1 "incidental" case. Except for
      tumours discovered on nephrectomies or autopsy, a nephrectomy was performed in
      all cases. Death occurred 1 to 12 months after diagnosis in the recipients with
      metastatic tumours. A colic carcinoma was diagnosed 6 months after nephrectomy in
      one patient. The other 11 patients are doing well as the immunosuppressive
      treatment is being continued.

PMID- 8151541
TI  - [Can the quality of renal grafts be judged on basis of the organ donors?].
AB  - The aim of this study is to find brain dead organ donor parameters able to
      predict the functional value of a kidney graft after transplantation. It is a
      retrospective, multicenter study, set in the east of France (Besancon, Nancy,
      Reims, Strasbourg). All donors harvested over an 18 month period (n = 169), and
      kidney grafts transplanted in a recipient in the same region (n = 298) are
      studied. Recipients from another region receiving a kidney graft as well as
      kidney grafts transplanted in other regions are not studied. Parameters studied
      in the donor are: age, sex, etiology of brain death, vascular disease,
      hemodynamic stability, use of epinephrine, diuresis, creatinine level, graft
      preservation solution. Parameters studied in the recipient are: age, sex, first
      transplantation or not, cold ischemia duration, warm ischemia duration, early
      post-transplantation diuresis and creatinine level evolution, dialysis
      requirement, immunosuppression, creatinine level at 1, 6 and 12 month. During the
      early post transplantation period, 264 recipients recovered diuresis, and the
      creatinine level felt in 246 cases. 31 patients required dialysis. 12 months
      after transplantation, 128 patients had a normal graft function (creatinine level
      < 15 mg/l). No parameter in the donor was found able to predict kidney graft
      function after transplantation. In fact, it is the amount of several risk factors
      due to donor data, organ retrieval and preservation, and kidney transplantation
      which is responsible for the early graft function. This points out the importance
      of being very careful when there is already a risk factor due to old age or
      vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151542
TI  - [Lymphoproliferative lesions localized in the renal graft. A French multicenter
      study].
AB  - Thirty-two French transplant centers participated in the study of
      lymphoproliferative disease (LPD) confined to the renal allograft. For the period
      from 1952 to February 1993, 16 cases were recognized from 16,755 renal transplant
      recipients. The mean age of the patients was 44 years (range 19-67 years).
      Fourteen of these recipients received anti-lymphocyte globulin as induction
      therapy and 13 received cyclosporine as their maintenance immunosuppressive
      treatment. Acute rejection was reported in 9 cases and was treated with
      methylprednisolone in 6 cases and with mono- or polyclonal antibodies for 3
      episodes. The mean interval from transplantation to development of LPD was 14
      months (range, 1-144 months). Most of the patient (12/15) showed symptoms. Renal
      failure was noted in 7 recipients. Renal ultrasound demonstrated hydronephrosis
      in 4 cases, a hilar mass in 5 cases, a mass lesion within the graft in 2 cases.
      Pathological examination showed a high grade malignant lymphoma with extensive
      necrosis and atypical large cells. Immunohistochemical study was consistent with
      B-cell lymphoma in all of the 8 cases analyzed and monotypia was noted in 4
      cases. The presence of Epstein-Barr virus genome in the LPD was demonstrated in 5
      of the 6 cases studied. Nine patients were managed with discontinuation of
      immunosuppression and transplant nephrectomies. Four patients died. The remaining
      recipients are alive with no evidence of recurrence after 25 months (range 3-68
      months).

PMID- 8151543
TI  - [Characteristic aspects of vascular complications in renal transplantation in
      children].
AB  - In a series of 859 transplantations performed in children and adolescents from
      January 1973 to December 1992, vascular thrombosis accounted for 18% of all graft
      losses (2nd cause of graft failure), and 57% of early failures (within 2 months).
      Renal veins and arteries were equally affected. The young age of the donors and
      recipients constituted the main risk factor, thrombosis accounting for 40 and 37%
      respectively of all graft losses in donors and recipients < 5 years old. This
      explained the lower survival rate of these age groups after grafting, as reported
      in most published pediatric series. The prophylactic use of a low molecular
      weight heparin in high-risk grafts may help to decrease its incidence. A renal
      artery stenosis, located a few cm beyond the anastomosis in 2/3 of cases, was
      observed in 10% of grafts. Often severe hypertension (HBP) with cerebral
      complications, responsible for permanent sequelae in some cases, was the
      prominent symptom. Anti-hypertensive drug therapy was sufficient to control HBP
      in 40 cases out of 72, and in 10 of these, a spontaneous regression of the
      stenosis was remarked within a few months after repeated angiography.
      Transluminal angioplasty was used on 26 stenosis and was effective in 2/3 of
      cases; the recurrence rate, however, was 27%.

PMID- 8151544
TI  - [Imaging of vascular complications of renal transplantation].
AB  - The accuracy of color Doppler US (CDUS) for the detection of main renal
      transplant artery stenoses is excellent (Se 92%; SP 99%). Whereas the sensitivity
      of CDUS is still unsatisfactory for the detection of arterial branch stenosis (Se
      70%), it has become higher than previously reported because of the ability of
      color flow images to identify hemodynamic changes at the site of stenosis and
      focal downstream repercussions in the case of tight stenosis. Color Doppler US is
      a valuable method in the detection of segmental infarction or large areas of
      cortical necrosis. However, small superficial cortical perfusion defects are
      usually undetectable by color Doppler. Contrast-enhanced MRI appears to be more
      accurate than color Doppler US; it is useful in confirming the diagnosis of
      infarction and detecting small infarcts missed by color Doppler US, and provides
      an accurate evaluation of the extent of the infarct; Spectral features (reflux
      during the whole diastole) obtained from renal arteries in case of acute renal
      vein thrombosis are suggestive but not specific since they can be observed in the
      case of severe acute rejection with cortical necrosis. Such findings associated
      with a lack of venous Doppler signals in the whole kidney are highly suggestive
      of renal transplant vein thrombosis. Post-biopsy arteriovenous fistulas and false
      arterial aneurysms are accurately detected by color Doppler Imaging. Color
      Doppler appears to be the primary Imaging modality for early detection of renal
      allograft vascular complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151545
TI  - [Value of renal scintigraphy in the diagnosis of vascular complications of renal
      transplantation].
AB  - Nuclear medicine can make an efficient contribution to the diagnosis and
      monitoring of renal disease and to the assessment of therapeutic interventions in
      the field of renal transplantation. The new radio pharmaceutical MAG 3 labelled
      with 99mTc provides renal imaging of quality in patients with impaired renal
      function and enables quantitative evaluation of renal function. We report on
      radionuclide evaluation, with special emphasis on the analysis of the vascular
      component of the scintigram, in the different clinical situations (i.e. renal
      failure) that may compromise the outcome of a successful renal transplant.

PMID- 8151546
TI  - [Prevalence of severe arterial hypertension in patients with renal grafts and
      surgical indications. Experience of the La Pitie Hospital].
AB  - Five hundred eighty five renal transplantations were performed in our group from
      January 1982 to December 1992. The observed incidence of hypertension in this
      group is 45%. Invasive treatment was indicated in 20 hypertensive patients
      (3.4%): 4 patients had bilateral-nephrectomy and 16 patients were treated for
      renal artery stenosis. This last group consisted of 12 men and 4 women (mean age
      of 36 years), who received a cadaveric transplant. 7 patients were hypertensive
      prior to transplantation. Only 25% of the patients received cyclosporine. Initial
      nephropathy was a glomerular in 9 cases. Before surgical treatment, an average of
      3.2 anti-hypertensive drugs were necessary to control arterial pressure.
      Percutaneous transluminal angioplasty was indicated in 11 patients, whereas
      surgical correction of arterial stenosis was realized in 6 cases. Angioplasty was
      associated with poor results (persistent HTA and renal failure in 7 out of 11
      patients). After surgery of renal artery, all patients had normal blood pressure.
      Renal artery stenosis would require surgical treatment, when possible. If not,
      percutaneous transluminal angioplasty will be proposed. The most efficient
      surgical procedure seems to be resection of the structure and termino-terminal
      anastomosis. When usable, internal iliac artery can be sutured beyond the
      stenosis.

PMID- 8151547
TI  - [Techniques and complications of interventional radiology in vascular diseases of
      transplanted kidneys].
AB  - The authors present a general review on the various techniques of interventional
      radiology in the treatment of vascular complications of renal transplants.
      Arterial stenosis require generally percutaneous transluminal angioplasty;
      arterial stenting is justified in cases of multiple restenosis and occluding
      dissection. Arterial thrombosis is treated by fibrinolysis or clot aspiration.
      Treatment of venous complications, such as stenosis or thrombosis, require
      analogous methods. Arterio-venous fistula and arterial aneurysms due to renal
      biopsy can be obliterated by dissection with a guide wire, or dropping of
      metallic coils, or electrical embolization. The authors emphasize the technical
      aspects, the difficulties and the complications of these procedures. The most
      frequent complication is the spasm of the renal transplant artery, which may lead
      to thrombosis. Arterial wall rupture and dissections are very rare. Hematoma at
      the puncture site of the arterial access are frequent; they may lead to false
      aneurysm, which can be treated also by noninvasive methods of interventional
      radiology.

PMID- 8151548
TI  - [Percutaneous endoluminal angioplasty of the transplanted kidney. Long-term
      follow-up].
AB  - A hundred and ninety five percutaneous transluminal angioplasty (PTA) of a renal
      transplant artery were attempted before january 1st, 1990 in 151 patients.
      Analysis of the series was essentially based on follow-up after PTA. PTA was
      initially successful in 85% of the patients. Restenoses occurred in 30% of the
      patient. They were usually amenable to repeat PTA. Restenosis rate after repeat
      PTA was of 26%. The five year secondary patency rate of the renal artery was over
      85%. After a successful PTA, the blood pressure, the number of antihypertensive
      drug per patient and serum creatinine returned to a level close to their basal
      value within few days and remained stable long. After an immediate failure of
      PTA, secondary patency rate of the renal transplant artery was over 80% at one
      year. Blood pressure returned to a level close to its basal value. But, that
      improvement was slower (1 to 6 months) and antihypertensive drug regimen and
      serum creatinine remained stable. We conclude that PTA is an effective treatment
      at long term of hypertension and of decline in renal function due to stenoses of
      renal transplant arteries. However PTA carried some risks and should be attempted
      only stenoses of renal transplants arteries cause, severe hypertension resisting
      to medical therapy or decline in renal function.

PMID- 8151549
TI  - [Influence of kidney procurement techniques on urologic and vascular
      complications of the transplantation].
AB  - Surgical complications of renal transplantation, rejection and infectious
      diseases are factors contributing to poor renal graft survival. Factors directly
      concerning the donor can be involved in graft failure: age, medical history,
      causes of donor brain death. Urologic or arterial anatomic variations are often
      the source of difficult surgical conditions during renal transplantation.
      Technical errors during graft procurement must be avoided such as excess of
      traction or coagulation. Failure in perfusion preservation. As few renal grafts
      are available, it is thus essential to obtain optimal conditions to avoid failure
      in cadaver donor graft linked to technical errors during organ procurement.

PMID- 8151550
TI  - [Magnetic resonance imaging in the diagnosis of myositis ossificans
      circumscripta].
AB  - A retrospective study of 5 cases, 4 of myositis ossificans circumscripta (MOC)
      and 1 of non-ossificans myositis, is presented. The clinical presentation was a
      painful soft-tissue swelling, and the final diagnosis was established by biopsy
      in 3 cases and clinical evolution in 2 cases. Different types of imaging
      techniques were performed: 4 MRI, 2 arteriographies, 3 Tc 99m scintigraphies, 3
      US, 3 CT and plain film radiographs for all patients. MOC is a benign process (as
      opposed to myositis ossificans progressiva, which is an inherited pathology with
      a fatal prognosis) with 3 phases of evolution: an acute or pseudo-inflammatory
      phase, a sub-acute or pseudo-tumoral phase and a chronic phase with a spontaneous
      healing. The radiologic diagnostic findings are dependent of the phase of the
      disease. The calcifications are seen earlier with scintigraphy than plain films,
      with US being less helpful. A heterogenous mass and calcifications are seen with
      CT. MRI allows the characterization of oedema during the acute phase and
      sometimes can exclude a malignant process. MRI is the best method for an early
      diagnosis, the differential diagnosis and to follow the evolution.

PMID- 8151551
TI  - [1,5 Tesla MRI in focal nodular hyperplasia. Review of the literature apropos of
      7 cases].
AB  - Six patients with 7 focal nodular hyperplasia lesions were investigated with 1.5
      Tesla magnetic resonance imagery (MRI). Surgical specimens were obtained in all
      cases and histological examination confirmed the diagnosis of focal nodular
      hyperplasia. In all cases, the tumour was isointense on the T1 weighted
      sequences. On the T2 weighted sequences in six cases, the tumour gave a
      hypersignal compared with the surrounding healthy liver tissue. Central scar
      tissue was found in all the lesions. On the T2 weighted images, the center gave a
      hypersignal 4 times and a hyposignal 3 times. Gadolinium injection on the echo
      gradient sequences (GRASS) showed product uptake suggestive of vessels within the
      central scar in one case. The report in the literature confirm the variability of
      focal nodular hyperplasia depending on the magnetic field used. In 1.5 Tesla MRI
      an isointense signal on at least one sequence would appear to be sufficient for
      the diagnosis of focal nodular dysplasia if the tumour is homogeneous and if the
      central scar is hyperintense in T2 sequences.

PMID- 8151552
TI  - [Echography in acute intestinal occlusion in ascariasis].

PMID- 8151553
TI  - [Spontaneous intramural hematoma of the esophagus. Apropos of a case].
AB  - The authors report a case of spontaneous intramural haematoma of the oesophagus.
      This is a rare observation which usually occurs in association with oesophageal
      hyperpressure and sometimes with impaired haemostasis. The strategy for diagnosis
      is based on tomodensitography and also endosonography and magnetic resonance
      imagery.

PMID- 8151554
TI  - [Late abdominal metastases of primary meningeal melanoma. Contribution of MRI].
AB  - A case of abdominal metastasis from primary meningeal melanoma is reported. MR
      imaging demonstrated hyperintensity on T1-weighted images in all the lesions and
      suggested their melanotic nature.

PMID- 8151555
TI  - [Complication of a central venous catheter related to malposition in the Braine
      vein. Contribution of x-ray computed tomography].
AB  - We report one case of emergency related malposition central venous catheter in
      left superior intercostal vein. The CT examination corroborate the venous
      perforation, showing contrast media effusion in mediastinum, pericardium and
      pleural cavities.

PMID- 8151556
TI  - [Imaging techniques in the diagnosis of brain lesions in eclampsia. Apropos of a
      case].
AB  - Eclampsia is defined as the development of convulsion and/or coma during
      pregnancy. Physiopathology remains unclear. We report a case of eclampsia and
      review the literature. CT, MR and angiographic findings are described. Value of
      various techniques is discussed.

PMID- 8151557
TI  - [Evaluation of the diagnostic contribution of a test. Main information indices].
AB  - Evaluating a new diagnostic test is an essential step required before using a new
      examination technique. The information concerning the disease provided by the
      test must be examined in terms of diagnostic value and cost. A test can be
      evaluated using several indexes. For tests giving binary results, the main
      information indexes were defined and the calculation of the index was illustrated
      by an example. The sensitivity, specificity, the Youden index, and the positive
      and negative predictive values were presented together with the likelihood and
      odds-ratio. For tests giving quantitative results, the analysis of the ROC curves
      was discussed. Indexes were interpreted in terms of disease prevalence, the
      modalities (diagnosis, screening) for applying the test, the sampling technique
      for the tested population, the gain in diagnosis, and cost of the examination.

PMID- 8151558
TI  - [Memories of a X-ray bulb. 3: Return to Paris. Progress of radiology].

PMID- 8151559
TI  - [High-resolution x-ray computed tomography of bronchiolo-alveolar carcinoma].
AB  - Bronchioloalveolar cell carcinoma may cause three main patterns on CT: solitary
      nodule, parenchymal consolidation, and multicentric disease. The nodules usually
      have spiculated margins and frequently contain bubble-like lucencies or pseudo
      cavitation. When presenting as consolidation, this is due mainly to mucin
      secretion and results in areas of lower attenuation than soft tissue.
      Multicentric disease is characterized by the presence of multiple nodules which
      may mimic metastatic disease. Although bronchioloalveolar cell carcinoma may
      cause different patterns on high-resolution CT, certain CT findings are
      sufficiently characteristic to suggest the underlying diagnosis.

PMID- 8151560
TI  - The mechanism of action of methotrexate in rheumatoid arthritis: the search
      continues.

PMID- 8151561
TI  - Synovial tissue implants from patients with rheumatoid arthritis cause cartilage
      destruction in knee joints of SCID.bg mice.
AB  - OBJECTIVE: To establish in SCID.bg mice a model in which joint destruction is
      initiated by human inflammatory cells from patients with rheumatoid arthritis
      (RA). METHODS: Development of a surgical technique and immunohistologic analysis.
      RESULTS: Initial experiments with single cell suspensions failed because more
      than 70% of the cells injected intraarticularly left the mouse knee joint within
      16 h without causing destruction. This was observed with peripheral blood
      mononuclear cells, T cell lines reactive to mouse or rat collagen type II, and
      synovial mononuclear cells. Cell immigration was reduced but not prevented by
      preactivation with mitogens. In contrast, small tissue implants from human
      synovial membrane which were transferred by surgical intervention into mouse knee
      joints remained at the site of injection and could be easily localized within the
      mouse joint (observation period up to 8 weeks). The human synovial membrane
      implants induced pannus formation and erosion of cartilage and bone while only a
      mild and transient synovitis was observed with normal synovial membrane and
      control tissues like human thymus. The predominant cells at the site of
      destruction were human (CD68+) and murine (Mac-2+) monocytes/macrophages.
      CONCLUSION: The human/murine SCID arthritis is a useful model for studying
      pathogenetic aspects of joint destruction as well as effects of new drugs or
      novel treatment strategies.

PMID- 8151562
TI  - Induction of experimental antiphospholipid syndrome in naive mice with purified
      IgG antiphosphatidylserine antibodies.
AB  - OBJECTIVE: It is accepted that antiphospholipid syndrome (APS) is due to the
      presence of anticardiolipin antibodies (aCL). Since phosphatidylserine is a
      negatively charged phospholipid, we tried to demonstrate the pathogenic role of
      antiphosphatidylserine in APS. METHODS: We used affinity purified IgG
      antiphosphatidylserine antibodies from sera of 2 patients with APS characterized
      by recurrent thromboembolic phenomena, recurrent fetal loss and prolonged
      activated partial thromboplastin time (aPTT). In one patient the
      antiphosphatidylserine Abs were the main antiphospholipid antibody (aPL) while
      the 2nd patient also had pathogenic aCL. The purified antibodies were passively
      infused into the tail vein of mice. The mice were mated and we followed them for
      manifestations of APS. RESULTS: Passive infusion of IgG but not IgM
      antiphosphatidylserine antibodies to pregnant ICR mice resulted in increased
      fetal resorption rate (40%), lower mean weights of the placentae and fetuses and
      prolonged aPTT (82 s). Antiphosphatidylserine antibodies were detected in the
      placentae. CONCLUSIONS: Our results point to the pathogenic role of
      antiphosphatidylserine antibodies and emphasize the importance of looking for the
      presence of antiphosphatidylserine Abs in sera of patients with clinical
      manifestations compatible with APS even in the absence of aCL Abs.

PMID- 8151563
TI  - Comparison of aminobenzoate potassium and placebo in the treatment of
      scleroderma.
AB  - OBJECTIVE: To determine the safety and efficacy of aminobenzoate potassium (KPAB)
      in treating the skin manifestations of scleroderma. METHODS: Via a 48-week
      prospective, randomized, double blind, placebo controlled trial we compared the
      efficacy of KPAB 12 g/day with matching placebo. Outcome measures included skin
      mobility and thickening scores, patient and physician global assessments and,
      measurements of maximal oral aperture and hand range of motion. RESULTS: Of 146
      patients who entered the study, 76 (52%) completed. Demographics of the study
      population included age 49 +/- 13 years, 83% women, mean (range) disease duration
      was 104 (7-600) months. There were no differences in the demographics of the KPAB
      vs placebo nor the group that completed the study compared with the withdrawal
      group. There were no clinical or statistically significant differences between
      the KPAB and the placebo treated groups in any of the outcome measures. Subgroup
      analyses of skin mobility and skin thickening based on age, extent of disease,
      severity of disease, duration of disease and involved vs uninvolved skin were
      performed, but no differences were noted. The overall compliance to the medical
      regimen was > or = 75% in 93% of patients completing the study. Eighteen patients
      in the KPAB group and 6 placebo patients withdrew due to adverse drug reactions
      (ADR). The most common withdrawals for ADR were gastrointestinal intolerance and
      headaches. All ADR resolved following withdrawal of medication. CONCLUSION: KPAB
      did not alter the skin changes of scleroderma in a group of patients with
      relatively longstanding stable disease. KPAB was reasonably well tolerated in
      this group of patients.

PMID- 8151564
TI  - Genetic and immunological differences between Japanese patients with diffuse
      scleroderma and limited scleroderma.
AB  - OBJECTIVE: To study the association between HLA-DR and scleroderma (SSc), subsets
      of SSc, and autoantibodies in SSc. METHODS: HLA-DR antigens were determined in 45
      Japanese patients with SSc. The association between HLA-DR and SSc, subsets of
      SSc, and autoantibodies was analyzed in 22 patients with SSc excluding mixed
      connective tissue disease (MCTD)/overlap syndrome (OL). RESULTS: When the 20
      patients with MCTD and 3 patients with OL were excluded from the original patient
      group, a significant increase of HLA-DR2 was observed (59 vs 29% of controls, p <
      0.01). The frequency of DR2 increased to 69% in patients with diffuse SSc (p <
      0.01). DR1, which was not found in diffuse SSc, was found in 2 of 9 patients with
      limited SSc. The frequency of DR2 was significantly higher in patients with
      antitopoisomerase I (10/12, 83%, p < 0.05). In contrast, DR1 was found only in 2
      patients with anticentromere antibodies (ACA), and all 5 patients with ACA had no
      HLA-DR2 (p < 0.01). CONCLUSION: Our results suggest that different HLA-DR markers
      may be associated with the production of distinct autoantibodies in diffuse SSc
      and limited SSc.

PMID- 8151565
TI  - Reactive arthritis: incidence, triggering agents and clinical presentation.
AB  - OBJECTIVE: To study the incidence and presenting clinical and microbiological
      features in subgroups of reactive arthritides. METHODS: In a defined community
      and during a 2-year period, we studied prospectively patients between 18 and 60
      years with onset of suspected reactive arthritis, primarily seen by general
      practitioners. RESULTS: Annual minimum incidence of Chlamydia induced arthritis
      (n = 25) was 4.6 and of arthritis triggered by enterobacteria (n = 27)
      5.0/100,000 individuals between 18 and 60 years. Triggering infections were
      asymptomatic in 36 and 26%, respectively. Patients with self-limiting arthritis
      without identified triggering agents (n = 60, incidence 11.0/100,000) had a
      normal prevalence of HLA-B27 and a more heterogeneous pattern of arthritis.
      CONCLUSION: Our epidemiological study confirms suggested high incidence rates of
      reactive arthritides. Reactive arthritides must be considered in early arthritis,
      even without symptoms of triggering infections.

PMID- 8151566
TI  - Treatment of severe refractory uveitis with intravenous cyclophosphamide.
AB  - OBJECTIVE: We assessed the efficacy of intravenous (iv) cyclophosphamide therapy
      for patients with uveitis. METHODS: Eleven patients with uveitis were treated
      with iv cyclophosphamide. Patients were from a tertiary care, referral practice,
      had failed oral corticosteroid therapy, and had disease that interfered with
      activities of daily living. RESULTS: Only 5 patients benefitted and the
      improvement was sustained without additional immunosuppression in only 2
      patients, one of whom had only mild eye disease and was receiving
      cyclophosphamide for a central nervous system vasculitis. Four patients worsened
      during the therapy. CONCLUSION: Although iv cyclophosphamide may have fewer risks
      than daily, oral cyclophosphamide, the majority of patients with uveitis do not
      experience a sustained benefit from this therapeutic approach.

PMID- 8151567
TI  - Seroreactivity to Borrelia burgdorferi antigens in the absence of Lyme disease.
AB  - OBJECTIVE: To determine the background levels and specificity of antibody to
      Borrelia burgdorferi by Western blot (immunoblot) in an area nonendemic for Lyme
      disease, and to correlate antibody specificity with clinical or serologic
      findings. METHODS: In a prospective survey by consecutive sampling, serum was
      obtained from patients referred to a tertiary care referral center in a rural
      area of Pennsylvania not endemic for Lyme disease. A total of 207 consecutive
      referrals to a rheumatology clinic over a 3-month period from September, 1991
      were divided into 3 groups. Those referred because of a positive Lyme serology
      (Group 1) were compared with patients having positive antinuclear antibodies or
      rheumatoid factor (Group 2) and with controls having no rheumatic complaints
      (Group 3). RESULTS: Antibody to at least one protein of B. burgdorferi was seen
      in over 40% of patients. Reactivities to the heat shock proteins and the 41 kDa
      flagellar antigen accounted for the majority of positive bands. There were no
      differences observed between the 3 groups, and no significant correlation between
      Western blot and ELISA findings in the absence of Lyme disease. CONCLUSION: We
      conclude that significant levels of antibody to B. burgdorferi may be seen on
      Western blotting in patients who have not been exposed to this organism by
      clinical or epidemiologic criteria. The antibodies detected may be natural
      antibodies, or may result from exposure to homologous antigenic epitopes on other
      organisms. The definition of a positive Western blot in the diagnosis of Lyme
      disease should incorporate the background levels of reactivity seen in nonexposed
      populations. Criteria for positivity should focus on the presence of antibody to
      the more specific proteins of B. burgdorferi.

PMID- 8151568
TI  - Secretory immune response and clinical sequelae of Salmonella infection in a
      point source cohort.
AB  - OBJECTIVE: To determine the kinetic isotypic serum and secretory immune response
      to Salmonella enteritidis in a cohort of individuals exposed to the organism in a
      single food source outbreak of dysentery. To determine the clinical outcome and
      immunogenetics of the exposed cohort and to correlate these features with the
      immune response. METHODS: Following a single point source outbreak of Salmonella
      enteritidis, a cohort of dysenteric individuals were ascertained using a reactive
      arthritis screening questionnaire (QUEST). Serum and stimulated saliva samples
      were obtained at 6, 12, and 24 months following the outbreak of dysentery;
      examinations were conducted at the same time. Two unexposed control groups were
      ascertained: (1) general rheumatology clinic patients and (2) well nonarthritic
      family practice patients. An ELISA to determine quantitative IgA responses to
      Salmonella enteritidis lipopolysaccharide (LPS) was performed. RESULTS: Eleven of
      the 84 exposed individuals with dysentery developed reactive arthritis (ReA) of
      reactive enthesitis (ReE). There was a prolonged salivary IgA anti-LPS response
      in both the ReA/ReE and DYS (dysentery alone) patients compared with unexposed
      controls. A ratio of salivary IgA anti-LPS/serum IgA anti-LPS > 1 was associated
      with a good outcome (remission) of ReA, whereas a ratio < 1 was associated with
      chronic disease. CONCLUSIONS: There is a more prolonged humoral immune response
      to Salmonella LPS in exposed individuals than hitherto described. A risk factor
      in the prolongation of ReA is the inability to mount an appropriate specific
      salivary (secretory) immune response.

PMID- 8151569
TI  - Cytosolic Ca2+ concentration determinations in neutrophils stimulated by
      monosodium urate and calcium pyrophosphate crystals: effect of protein
      adsorption.
AB  - OBJECTIVE: To develop methods to correct for light scattering artifacts produced
      by monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD)
      crystals in the measurement of the levels of cytosolic free calcium, [Ca2+]i, in
      neutrophils and to quantitate the extent of association of neutrophils with
      crystals. METHODS: The association of neutrophils with crystals through binding
      of crystals onto the neutrophil plasma membrane and/or internalization was
      quantitated by mixing crystals with diphenyl hexatriene (DPH) loaded neutrophils
      and monitoring the fluorescence intensity of supernatants ("free" neutrophils)
      following gravity sedimentation of "free" crystals and neutrophils with
      bound/internalized crystals. The effects of precoating CPPD and MSUM crystals
      with IgG, plasma, serum and BSA on crystal-neutrophil association and [Ca2+]i
      were determined. RESULTS: MSUM produced a large increase in [Ca2+]i that reached
      maximal values in less than 1 min, whereas CPPD produced a smaller and slower
      increase in [Ca2+]i. IgG adsorbed onto CPPD increased the rate and extent of
      increase in [Ca2+]i. Heparinized plasma and serum adsorbed onto CPPD increased
      the extent but not the rate of increase in [Ca2+]i. CONCLUSION: [Ca2+]i increases
      induced by MSUM were not affected by IgG, serum or heparinized plasma precoating.
      IgG, serum, or heparinized plasma adsorbed into CPPD amplified neutrophil
      activation increasing the extent of the increase in [Ca2+]. Neither MSUM nor CPPD
      induced increases in [Ca2+]i were sensitive to precoating crystals with bovine
      serum albumin.

PMID- 8151570
TI  - Attitudes to alternative medicine by rheumatology outpatient attenders.
AB  - OBJECTIVE: To determine the proportion of rheumatology outpatient attenders who
      have sought "alternative medicine" treatment and their satisfaction with these
      services compared with the conventional hospital clinic. METHODS: A questionnaire
      survey was distributed to 314 rheumatology outpatients of a tertiary referral
      teaching hospital: 280 (89%) were sufficiently complete for analysis. RESULTS:
      114 patients (40%) had attended one or more alternative practitioners at some
      stage of their rheumatic illness. These patients were younger and statistically
      more satisfied with their treatment and doctor's attitude at the outpatient
      clinic than that received at the alternative center. They also believed their
      doctor was more approving of these visits and were equally satisfied with clinic
      treatment compared with patients who had never attended alternative therapists.
      CONCLUSION: Patients with rheumatic diseases who choose to continue with
      conventional care are likely to be less satisfied with alternative medicine and
      more satisfied with hospital outpatient treatment. We should be aware that a
      significant number of patients will try or have tried these alternative
      treatments but continue to attend without prejudice to their ordinary care.

PMID- 8151571
TI  - Alternative medicine use by rheumatology patients in a universal health care
      setting.
AB  - OBJECTIVE: To assess the prevalence, extent of use, and cost of alternative
      medicine by patients attending a rheumatology clinic. METHODS: Two hundred and
      thirty-five unselected consecutive patients attending a rheumatology clinic were
      evaluated by questionnaire to record their current use of alternative medicine
      practices. RESULTS: Sixty-six percent of patients had used alternative medicine
      interventions in the preceding 12 months; 54% used over the counter products, 39%
      spiritual aids (including prayer, relaxation, meditation), and 13% each had
      visited alternative practitioners or used dietary interventions. Patients in the
      upper middle income group and French speaking patients used more bought products,
      but no other differences were observed when the groups were analyzed according to
      level of education, income or cultural background. The current annual cost for
      the patients of alternative medical therapies was $100. CONCLUSION: Our results
      demonstrate a moderate use of alternative medicine by rheumatology patients,
      mostly inexpensive products and no cost spiritual aids. Universal health care may
      have a negative impact on the extent of use of more costly practices.

PMID- 8151572
TI  - Treatment of growth retardation in juvenile chronic arthritis with recombinant
      human growth hormone.
AB  - OBJECTIVE: To evaluate the effect of recombinant human growth hormone (rhGH) on
      the linear growth of children with persistently active juvenile chronic arthritis
      (JCA), most of whom were receiving steroid therapy. All of them were severely
      growth retarded, but had adequate GH secretion. METHODS: After monitoring height
      velocity for one year, children were treated for the following year with either
      12 IU/m2 or 24 IU/m2 of rhGH. During this period disease activity, drug
      treatment, dietary intake and bone maturation as well as linear growth were
      documented. RESULTS: There was a significant increase in height velocity in
      almost all children during the treatment period. Children with mild to moderate
      disease activity grew at a better rate than those with very active disease.
      Children with polyarticular disease responded better than those with systemic
      JCA. Those children receiving high dose rhGH grew significantly more than those
      on the low dose regimen. Bone maturation did not exceed chronological age.
      CONCLUSION: We conclude the rhGH significantly increases the height velocity
      during one year of treatment. However, its effect on ultimate adult height
      remains unknown. Thus extensive longterm studies are required to evaluate the
      risk benefit ratio of this costly treatment.

PMID- 8151573
TI  - Class II alleles in juvenile arthritis in Czech children.
AB  - OBJECTIVE: Patients with pauciarticular and polyarticular onset rheumatoid factor
      (RF) negative juvenile arthritis (JA) have been reported to have a variety of HLA
      associations. The reason for the differences found in several recent studies is
      not known. We compare a new series of patients investigated in Prague,
      Czechoslovakia with those we reported from Dallas. METHODS: Czech patients with
      JA (N = 153) were classified clinically using the same criteria as in our studies
      in Dallas. The RF negative group included 56 patients that had persistent
      pauciarticular disease, 42 pauciarticular with polyarticular course and 39 with
      polyarticular onset. RF was present in 13 additional patients. HLA class II
      alleles were determined by oligotyping as previously described from our
      laboratory. RESULTS: DRB1*0801 was increased and DRB1*0701 was decreased in all
      the RF negative groups. The persistent pauciarticular group was associated with
      DRB1*11 and DPB1*0201 and lacked the association with DRB1*1301 seen in Dallas.
      Also found in Prague and not in Dallas were an increase in the frequency of DR2
      in pauciarticular patients with early conversion and of DRB1*1201 in patients
      with iritis. Certain HLA associations (DRB1*0801, DPB1*0201) appear to be present
      in patients with JA in most studies; others (DRB1*1301, DPB1*0301) are more
      variable. CONCLUSION: The reason for differences in the HLA risk factors observed
      in our 2 populations is not known. Clinical heterogeneity not detected by our
      method seems the most likely explanation. Genetic and environmental factors may
      also play a role.

PMID- 8151574
TI  - Sjogren's syndrome with amyloid A presenting as multiple pulmonary nodules.
AB  - A 29-year-old woman presented with diffuse pulmonary nodular amyloidosis and was
      subsequently diagnosed as having Sjogren's syndrome. We believe that this is the
      first case of Sjogren's syndrome presenting with secondary amyloidosis of the
      lung.

PMID- 8151575
TI  - Nodular regenerative hyperplasia of the liver and primary Sjogren's syndrome.
AB  - Nodular regenerative hyperplasia (NRH) of the liver is a rare entity associated
      with autoimmune diseases, hematologic disorders and therapy with
      immunosuppressive agents. We describe a patient with primary Sjogren's syndrome
      and NRH of the liver, the first report of this association. The pathogenesis of
      NRH is not clear, but the presence of some type of circulatory disorder is
      suspected.

PMID- 8151576
TI  - Sacroiliitis in systemic lupus erythematosus.
AB  - A 19-year-old white woman with severe systemic lupus erythematosus developed
      symptomatic sacroiliitis early in her disease. Over the next 14 years she showed
      radiological progression of sacroiliitis. She had neither HLA-DR3 nor B27
      antigens. The rare coexistence of SLE and ankylosing spondylitis may not be
      determined solely by genetic factors; sacroiliitis may be just an infrequent
      manifestation of SLE.

PMID- 8151578
TI  - Rheumatology in philately.

PMID- 8151577
TI  - Renal coagulopathy, thrombocytopenia, and the anticardiolipin antibody:
      therapeutic response to corticosteroids and aspirin but not anticoagulation.

PMID- 8151579
TI  - Serologically active, clinically quiescent systemic lupus erythematosus--longterm
      followup.

PMID- 8151580
TI  - Mediastinal emphysema developing after a pulmonary function test in a patient
      with dermatomyositis.

PMID- 8151581
TI  - Chromonychia with systemic lupus erythematosus.

PMID- 8151582
TI  - Physical disability and psychological well being in recent onset rheumatoid
      arthritis.
AB  - OBJECTIVE: The association between self-report physical disability scores and
      psychological well being in patients with rheumatoid arthritis (RA) has been
      described in several recent publications on patients with widely varying disease
      durations. We describe the results of a study into these relationships in
      patients with RA with a disease duration of less than 1 year. METHODS: In this
      cross sectional study on 113 patients with recent onset RA disability was
      assessed with 3 self-report indices and with measurement of grip strength.
      Correlation coefficients between disability measures and disease activity
      measures (joint tenderness/swelling score, erythrocyte sedimentation rate
      [ESR)]), psychological well being (cheerful mood, depressive mood, and anxiety),
      and demographical variables were calculated; hierarchical regression analysis was
      done with disability measures as the dependent variables. RESULTS: All disability
      scales were correlated moderately strongly with the joint score and ESR, and with
      psychological well being. No relation was found with age, sex, marital status, or
      rheumatoid factor status. Regression analysis showed the variance of 9-15% in
      disability could be explained by psychological well being after disease activity
      had been controlled for. CONCLUSION: Patients with recent onset RA appear not to
      be obviously different with respect to the moderately strong association between
      physical disability and psychological well being from patients with RA of longer
      duration in other published reports.

PMID- 8151583
TI  - Cause of death in 81 autopsied patients with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the cause of death and complications in a series of
      autopsied patients with rheumatoid arthritis (RA). METHODS: A clinicopathological
      study of 81 autopsied patients with RA was performed. RESULTS: In order of
      frequency, the causes of death were infection (23.5%), heart disease (17.3%),
      respiratory failure (9.9%), renal failure (9.9%), and gastrointestinal disease
      (9.9%). Observed complications of RA were systemic angiitis in 25 cases (30.8%),
      systemic amyloidosis in 17 cases (21.0%), and pulmonary fibrosis in 28 cases
      (34.6%). No patient had both angiitis and amyloidosis simultaneously. The
      prevalence of systemic angiitis tended to decrease during the study period (1960
      1990), while systemic amyloidosis tended to increase. CONCLUSION: The cause of
      death in RA is difficult to analyze accurately because RA itself is a chronic
      systemic inflammation disease.

PMID- 8151584
TI  - Expression of autocrine motility-like factor in rheumatoid synovial fluid.
AB  - OBJECTIVE: To examine whether a cytokine, autocrine motility factor (AMF), plays
      a role in rheumatoid arthritis (RA). METHODS: We investigated the chemokinetic
      activity of synovial fluids (SF) obtained from patients using a unique protein
      free culture fibrosarcoma Gc-4 PF, the motility of which is specifically
      dependent on the cytokine. RESULTS: Treatment of the cells with the SF stimulated
      their phagokinetic motility by 1.4, 1.8, and 2.1-fold at protein concentrations
      of 100, 250 and 500 micrograms/ml, respectively. This dose dependent response was
      observed in all 3 patients with classical or definite RA. In contrast with Gc-4
      PF cells, the SF did not stimulate the motility of Gc-4 SD cells that have little
      response to AMF. The ability of this chemokinetic activity to block binding of
      the monoclonal antibody to the receptor for AMF was demonstrated on immunoblots.
      CONCLUSION: Based on these results, it is suggested that the motile activity may
      be AMF. The possible role of the cytokine in the pathogenesis of RA is discussed.

PMID- 8151585
TI  - Association of HLA-DR5 with mucocutaneous lesions in patients with rheumatoid
      arthritis receiving gold sodium thiomalate.
AB  - OBJECTIVE: To investigate the possible association between HLA antigens and
      adverse reactions to gold sodium thiomalate therapy (GSTM). METHODS: Ninety
      consecutive patients with rheumatoid arthritis (RA) were studied for possible
      association between HLA antigens and adverse reactions to GSTM therapy. RESULTS:
      HLA-DR5 was significantly increased in patients who developed gold induced
      mucocutaneous lesions. On the other hand, patients with RA carrying B8 and DR3
      antigens are of a high risk of developing proteinuria after gold therapy. A very
      interesting finding was the low incidence of DR7 antigen in patients who
      developed adverse reactions to GSTM. We also report the relationship between B27
      antigen and chrysiasis due to gold therapy. CONCLUSION: Our results support
      suggestions that the DR7 antigen provides a protective effect against gold
      toxicity. We also found a strong association between DR5 and mucocutaneous
      lesions in patients with RA treated with GSTM.

PMID- 8151586
TI  - Efficacy of additive DMARD therapy in patients with rheumatoid arthritis. Double
      blind controlled trial using bucillamine and placebo with maintenance doses of
      gold sodium thiomalate.
AB  - OBJECTIVE: To examine the efficacy of the addition of small doses of additional
      disease modifying antirheumatic drugs (DMARD) to ongoing DMARD treatment
      [additive DMARD therapy (ADT)]. METHODS: A 3-month prospective, double blind,
      randomized, placebo controlled study was performed using either 100 mg/day of
      bucillamine (Buc) or an inactive placebo (P1). Two groups of 12 patients each who
      had experienced an insufficient benefit from gold sodium thiomalate (GSTM) alone
      were enrolled in the study. RESULTS: The addition of Buc proved more beneficial
      than P1 regarding improvement in disease activity (p = 0.0032) and drug
      usefulness (p = 0.0025). A significant within group improvement was observed in
      joint swelling count, the Lansbury activity index, erythrocyte sedimentation rate
      and C-reactive protein. However, the difference in the clinical variables between
      the 2 groups was minimal. CONCLUSION: The usefulness of ADT was suggested by this
      trial; however, further confirmation by additional studies is still needed.

PMID- 8151587
TI  - Incidence, prevalence and possible risk factors for pneumonitis in patients with
      rheumatoid arthritis receiving methotrexate.
AB  - OBJECTIVE: Methotrexate (MTX) is being used increasingly to treat rheumatoid
      arthritis (RA). Pneumonitis is a serious side effect of MTX therapy (P-MTX). Our
      aim was to determine in patients with RA the incidence and prevalence of P-MTX in
      Western Australia and identify risk factors for the development of this adverse
      reaction. METHODS: Patients with P-MTX were identified by (a) direct
      communication with rheumatologists in Western Australia, (b) use of a
      computerized clinical database, (c) questionnaire inquiry of all other
      rheumatologists in Australia. Possible risk factors for P-MTX were examined using
      age/sex matched case controls selected from the computerized clinical database.
      RESULTS: Ten definite and 3 probable cases of P-MTX were identified. Local
      incidence of P-MTX was 1/35.4 patient years MTX treatment; if definite and
      probable cases are included (1/49.6 patient years MTX treatment for definite
      cases alone). Twelve patients with P-MTX were compared with 24 age/sex matched
      controls. A shorter duration of MTX treatment and a higher incidence of
      preexisting lung disease were observed in P-MTX cases but these differences were
      not statistically significant. No difference was observed between the P-MTX and
      control patients with respect to rheumatoid factor, duration of RA, use of
      tobacco, dose of MTX, serum creatinine, creatinine clearance or concurrent
      treatment with aspirin, nonsteroidal antirheumatic drugs or prednisolone.
      CONCLUSION: Our results indicate that in hospital clinic patients with RA
      pneumonitis is a common adverse reaction. They suggest that hypersensitivity is
      probably responsible for most cases of pneumonitis associated with MTX, but
      preexisting lung disease may confer increased risk.

PMID- 8151588
TI  - The effect of methotrexate on ex vivo lipoxygenase metabolism in neutrophils from
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To examine the effect of methotrexate (MTX) administered in vivo on
      the production of the 5-lipoxygenase (5-LO) metabolites of arachidonic acid by
      neutrophils from subjects with rheumatoid arthritis. METHODS: Neutrophils were
      isolated from peripheral blood samples taken 12 h before and 12 h after the
      ingestion of an oral dose of MTX and stimulated in vitro by calcium ionophore
      A23187. Lipid extracts of cell suspensions were assayed for leukotriene B4
      (LTB4), the all-trans isomers of LTB4, 20-hydroxy LTB4 and 5
      hydroxyeicosatetraenoic acid by high pressure liquid chromatography. RESULTS: An
      increase in the production of all measured 5-LO metabolites was seen between the
      pre and postdose assessments. CONCLUSION: Our results do not support the putative
      inhibitory effect of MTX on 5-LO metabolism.

PMID- 8151589
TI  - Current practices for monitoring ocular toxicity related to hydroxychloroquine
      (Plaquenil) therapy.
AB  - OBJECTIVE: Growing interest in aggressive early management of rheumatoid
      arthritis (RA) with hydroxychloroquine (alone or in combination with other
      immunomodulating drugs) is reason to review current practices for monitoring
      ocular toxicity in patients who take antimalarial therapy. METHODS: We surveyed
      by mail all ophthalmologists and rheumatologists in the State of Indiana about
      their practices in this regard. RESULTS: Twenty-nine of 31 rheumatologists (94%)
      responded. All but one recommended ophthalmologic examinations every 6 months and
      41% would leave the choice of testing procedures to the ophthalmologist. Fifty
      percent had discontinued hydroxychloroquine because of a patient's failure to
      make and/or keep an appointment with the ophthalmologist. Of 213 ophthalmologists
      surveyed, 150 (70%) responded. Seventy-nine percent recommended semiannual
      examinations. Funduscopy, visual acuity, and color vision tests were reported to
      be performed routinely. Eleven of 13 retina specialists (85%), but only 25% of
      127 general ophthalmologists, would obtain macular photographs (p < 0.001). Forty
      two percent of general ophthalmologists, compared with 8% of retina specialists,
      would perform computerized perimetry (p < 0.001). Recognition of retinal
      hyperpigmentation as a classic sign was surprisingly low in both groups.
      Concurrent review of the medical records of 24 patients with RA or systemic lupus
      erythematosus showed extremely variable followup intervals for ophthalmologic
      examination; 7 of the 24 patients had no record of an ophthalmologic evaluation.
      CONCLUSION: As interest in the early, aggressive management of RA continues to
      grow, significant education needs to be devoted to the monitoring and diagnosis
      of ocular toxicity of hydroxychloroquine by both rheumatologists and
      ophthalmologists.

PMID- 8151590
TI  - Lumping and splitting when assessing arthritis.

PMID- 8151591
TI  - Joint impairment is strongly correlated with disability measured by self-report
      questionnaires. Functional status assessment of individuals with rheumatoid
      arthritis in a population based series.
AB  - OBJECTIVE: To determine how well self-report functional ability reflects the
      impairment due to the arthritic process in rheumatoid arthritis (RA) and how much
      it is affected by other factors of health status. METHODS: We examined the
      relationships between self-report measures such as the Health Assessment
      Questionnaire (HAQ) and Arthritis Impact Measurement Scales (AIMS) and measures
      of impairment such as the Keitel function test (KFT), which is intended to
      reflect the degree of functional limitation of the joints, grip strength and
      radiological destruction as well as anxiety and depression in a population-based
      series of RA. RESULTS: First, the HAQ and AIMS had a high correlation coefficient
      (r = 0.89, p < 0.0001). Second, the above measures of impairment were more
      significant predictors of self-report functional measures than, for example,
      mental health perceptions. The AIMS scales also correlated well with the
      corresponding physical function of the KFT. CONCLUSION: Patients' self-report
      functional ability in RA reflects their physical impairment due to the arthritic
      joint disease and is less influenced by other factors such as emotional
      adjustment.

PMID- 8151592
TI  - Can specially trained physiotherapists improve the care of patients with
      rheumatoid arthritis? A randomized health care trial.
AB  - OBJECTIVE: To examine the influence of specially trained physical therapists (PT)
      on patterns and outcome of care, relating to inflammatory disease status as
      measured by disease outcomes. METHODS: Fifty-four patients were allocated at
      random to specially trained PT, and to traditional PT. Outcomes were measured at
      baseline and at 4 months by independent assessors. RESULTS: There was no
      statistically significant or clinically important difference in outcome between
      the 2 groups. The advice of specially trained PT significantly improved
      compliance with salicylates. CONCLUSION: The effectiveness of this therapy was
      not demonstrated, likely due to incomplete compliance along the therapeutic
      chain, beginning with the PT's report, through a variety of possible responses,
      and ending with patient outcome.

PMID- 8151593
TI  - Alternative medicine: science or superstition?

PMID- 8151594
TI  - Acute effects of misoprostol on digital circulation in patients with Raynaud's
      phenomenon.
AB  - OBJECTIVE: To determine whether the orally absorbable prostaglandin E1 analog
      misoprostol might be a suitable treatment for Raynaud's phenomenon (RP). METHODS:
      We tested the acute effect of a single 400 micrograms oral dose of misoprostol on
      digital hemodynamics. Eight patients with RP and 6 healthy volunteers were
      evaluated in a double blind, placebo controlled, crossover study. Hemodynamic
      outcome measures included fingertip skin temperature, finger systolic pressure,
      laser Doppler digital blood flow, and the skin temperature reactivity and
      rewarming response to a -5 degrees C cold challenge. RESULTS: We found no
      significant effects of misoprostol on digital circulation in either patients with
      Raynaud's or healthy subjects in any of the outcome measures. CONCLUSION: We
      conclude that misoprostol has no significant acute vasodilating properties in the
      digital circulation, and therefore it is not likely to be an effective adjunct to
      the treatment of RP.

PMID- 8151595
TI  - Herpes zoster infections in systemic lupus erythematosus: risk factors and
      outcome.
AB  - OBJECTIVE: To determine factors that influence the frequency and outcome of
      herpes zoster infection in patients with systemic lupus erythematosus (SLE).
      METHODS: In this case-central retrospective study, patients with a history of
      zoster infection were identified from our computerized database of 348 patients
      with SLE. Medical records were reviewed to establish activity of SLE at the time
      of zoster, as well as complications of the zoster infection. RESULTS: Fifty-five
      episodes of zoster occurred among 47 (13.5%) patients, at a rate of 16
      episodes/1000 patient-years of followup. Dissemination occurred in 6 episodes
      (11%), and was more frequent during immunosuppressive therapy [odds ratio (OR) =
      4.0]. Bacterial superinfection occurred in 5 (9%), resulting in one death from
      sepsis, and was increased among patients receiving prednisone > or = 60 mg daily
      (OR = 4.1). Compared to those without zoster, patients with zoster were
      significantly more likely to have previously had serious disease manifestations
      including nephritis, thrombocytopenia or hemolytic anemia, and to have received
      treatment with cyclophosphamide (all p < or = 0.05). However, 65% of zoster
      episodes occurred during mild or inactive SLE, when the majority of patients were
      receiving less than 20 mg prednisone daily and no immunosuppressive therapy.
      CONCLUSION: Herpes zoster infections occur at increased frequency among patients
      with SLE compared to the general population, and carry significant morbidity.
      Patients who have had severe manifestations of lupus are at greatest risk of
      zoster, though not necessarily at the time of disease flare or immunosuppressive
      therapy. If disease activity allows, a reduction in prednisone dosage may reduce
      the risk of bacterial superinfection during zoster episodes.

PMID- 8151596
TI  - Cerebral lesions in systemic lupus erythematosus detected by magnetic resonance
      imaging. Relationship to anticardiolipin antibody.
AB  - OBJECTIVE: To detect cerebral lesions in neuropsychiatrically symptomatic or
      asymptomatic patients with systemic lupus erythematosus (SLE) and investigate the
      relationship of these lesions to clinical and laboratory variables. METHODS:
      Brain magnetic resonance imaging was performed on 31 patients with SLE under the
      age of 50, including 2 patients with central nervous system (CNS) lupus and 29
      neuropsychiatrically asymptomatic patients. RESULTS: Abnormal high intensity
      spots on T2 weighted images were found in 10 patients (32%), of which 5 were
      neuropsychiatrically asymptomatic throughout the disease course. The high
      intensity spot was significantly associated with the presence of high levels of
      anticardiolipin antibody (aCL) of IgG isotype, livedo reticularis and CNS lupus.
      CONCLUSION: Our results suggest that asymptomatic cerebral lesions are not rare
      in patients with SLE and screening of aCL would be helpful in predicting cerebral
      lesions. A followup study of these asymptomatic patients is necessary to clarify
      the clinical significance of a high intensity spot.

PMID- 8151597
TI  - Single anticardiolipin measurement in the routine management of patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To examine the usefulness of a single measurement of anticardiolipin
      antibodies (aCL) in systemic lupus erythematosus (SLE) in routine clinical
      practice. METHODS: All 127 patients with SLE currently followed by our
      rheumatology unit had an aCL measurement on routine clinic review. Their charts
      were then reviewed for specific disease manifestations. Basic statistical
      correlations of the aCL result and the specific disease manifestations were
      performed, and the clinical utility of the aCL test assessed using Bayesian
      analysis. RESULTS: aCL was positive (> 2 SD) in 24% and was associated with
      recurrent fetal loss, thrombosis, cerebrovascular disease, livedo reticularis and
      digital infarcts. Bayesian analysis showed that a single positive aCL test
      increased the relative and absolute risk of all the above complications. The
      criterion of aCL positivity as > 15 units (2 SD) was associated with the highest
      relative risk. CONCLUSION: A single positive aCL test in routine management of
      SLE is a useful predictor of important clinical events.

PMID- 8151598
TI  - Characteristics of human immunodeficiency virus and chlorpromazine induced
      antiphospholipid antibodies: effect of beta 2 glycoprotein I on binding to
      phospholipid.
AB  - OBJECTIVE: To investigate the nature of the target epitope for human
      immunodeficiency virus (HIV) and chlorpromazine (CPZ) induced antiphospholipid
      antibodies (aPL) by evaluating the effect of the aPL cofactor (beta 2
      glycoprotein I) on phospholipid binding and to compare this with known binding
      patterns of infection induced and autoimmune aPL. METHODS: aPL positive sera from
      17 patients with HIV and 16 patients with schizophrenia treated with CPZ were
      tested and compared with aPL positive sera from 20 patients with syphilis and 35
      with autoimmune disease. Both the sera and either IgG fractions prepared by
      affinity chromatography or IgM fractions prepared by euglobulin precipitation and
      gel filtration were tested for binding to cardiolipin (CL) in ELISA in the
      presence and absence of purified human beta 2 glycoprotein I (beta 2-GPI).
      Competition studies evaluated biotinylated CPZ IgM aPL binding and the effect on
      this of added aPL, placental anticoagulant protein I--a phospholipid binding
      protein that inhibits autoimmune aPL--and CL vesicles. RESULTS: HIV IgG aPL
      binding to CL was inhibited by beta 2-GPI (51-53%), like syphilis IgG aPL and in
      contrast to autoimmune IgG aPL. CPZ IgM aPL, like autoimmune IgM aPL, bound more
      efficiently in the presence of beta 2-GPI, with binding increases of 31-149%.
      Binding of biotinylated CPZ IgM aPL to CL was competitively inhibited by
      autoimmune IgG aPL (47%) and CPZ aPL (92%) but not by HIV IgG aPL or normal IgG.
      Placental anticoagulant protein I and CL vesicles completely prevented binding of
      CPZ IgM aPL to CL (100 and 96% inhibition, respectively). CONCLUSIONS: Findings
      indicate that CPZ aPL resembles the autoimmune aPL, whereas aPL found in HIV
      infection do not appear to be of autoimmune type.

PMID- 8151599
TI  - Identical blood pressure levels and slower heart rates among nurses during night
      work and day work.
AB  - To investigate the effects of shift work on circadian BP variation, ambulatory
      24h BP monitoring was performed during the day shift and night shift on 17
      normotensive nurses. On both shifts, BP and heart rate increased in the working
      phase and decreased during sleep. The mean 24h BP and heart rate were identical
      in the two shifts. During sleep, BP was lower and the heart rate was slower in
      the day shift (night sleep) perhaps because of deeper sleep than during daytime
      sleep associated with the night shift. During work, BP was identical but the
      heart rate was significantly slower during the night shift. These data suggest
      that the circadian BP variation is determined largely by the sleep-wakefulness
      cycle and that the heart rate is also influenced by the internal body clock.

PMID- 8151600
TI  - Enhanced secretion and impaired natriuretic action of atrial natriuretic peptide
      in response to hypertonic saline infusion in patients with essential
      hypertension.
AB  - To clarify the natriuretic action of endogenous atrial natriuretic peptide (ANP)
      in patients with essential hypertension (EHT), we examined the relationship
      between ANP release and urinary sodium excretion in response to hypertonic saline
      infusion. Plasma ANP levels increased from 13.3 +/- 2.0 pg/ml to 37.0 +/- 3.0
      pg/ml in patients with EHT and from 9.2 +/- 1.5 pg/ml to 21.1 +/- 4.0 pg/ml in
      normal subjects after the infusion. The area under the curve (AUC) of plasma ANP
      response was significantly higher in patients with EHT than in normal subjects (P
      < 0.05). There was a significant positive correlation between AUC and urinary
      sodium excretion in both groups (P < 0.01). However, the ratio of urinary sodium
      excretion to AUC was significantly lower in patients with EHT than in normal
      subjects (P < 0.01). These results suggest that impaired natriuretic response to
      endogenous ANP is one of the factors responsible for the development of EHT and
      that enhanced secretion of ANP in response to hypertonic saline infusion is a
      compensatory mechanism to the impaired natriuretic action of ANP in patients with
      EHT.

PMID- 8151601
TI  - Cardiovascular effects of cigarette smoking: ambulatory blood pressure and BP
      variability.
AB  - Cigarette smoking and hypertension are independent risk factors for
      cardiovascular disease, but the relationship between them is complex. Smoking
      raises BP acutely, yet in epidemiological studies smokers have lower clinic BP
      than nonsmokers. To explore this apparent paradox we have compared 24h ambulatory
      BP profiles and BP variability of smokers, before and after a week's abstention
      from smoking, and nonsmoking controls. There was no evidence of a significant
      acute pressor effect from smoking. All three groups had similar ABP profiles but
      smokers had significantly more variable BP than nonsmokers and variability
      increased still further after a week's abstention. An increase in BP variability,
      possibly related to changes in baroreflex sensitivity, is a further mechanism by
      which smoking may increase cardiovascular risk.

PMID- 8151602
TI  - Non-invasive ambulatory BP monitoring during the night: randomised comparison of
      different reading intervals.
AB  - Frequent measurements of BP during noninvasive monitoring could interfere with
      sleep, with consequent possible overestimation of nocturnal BP. We performed 24h
      noninvasive ambulatory BP monitoring (Space-Labs 90207) in 24 patients with
      essential hypertension twice, 1 week apart. Subjects were instructed to follow,
      as far as possible, a similar pattern of daily activity during the two sessions.
      The frequency of daytime readings (from 06.00 to 22.00 h) was kept constant in
      the two sessions (one every 15 minutes), while that of nocturnal readings (from
      22.00 to 06.00 h) varied in random order: every 15 minutes in session A and every
      60 minutes in session B. Mean sleep BP did not differ between session A (138/83
      mmHg (SD 15/10 mmHg)) and session B (138/83 mmHg (SD 14/10 mmHg)). The percentage
      reduction of ambulatory SBP and DBP from wake to sleep was 9.7% and 10.0%,
      respectively, in session A, and 14.0% and 14.1%, respectively, in session B (all
      P = NS). The duration of sleep was 6.1 hours (SD 2 hours) in session A and 6.0
      hours (SD 2 hours) in session B (P = NS). On average, 6.8% of nocturnal readings
      in session A and 7.6% of nocturnal readings in session B failed to pass the
      automatic editing criteria, but no hourly interval was lacking in valid
      measurements on both sessions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8151603
TI  - Nephropathy and changes in sodium-lithium countertransport kinetics in type 2
      (non-insulin-dependent) diabetes mellitus.
AB  - Previous studies of erythrocyte sodium-lithium countertransport activity, a
      putative genetic marker of essential hypertension, in Type I and Type II diabetic
      patients with nephropathy have given conflicting results. We have found changes
      in the maximum velocity (Vmax) and sodium-affinity constant (Km) of sodium
      lithium countertransport in Type I diabetic patients with diabetic nephropathy.
      In this study, sodium-lithium countertransport kinetics were measured in Type II
      diabetic patients with established diabetic nephropathy, matched uncomplicated
      Type II diabetic patients, non-diabetic patients with nephropathy and healthy
      control subjects. Mean standard sodium-lithium countertransport activity was not
      significantly increased in either of the groups of diabetic patients compared
      with the non-diabetic control groups. The Type II diabetic patients with
      nephropathy had a significantly reduced km and Vmax compared with the
      uncomplicated diabetic patients and non-diabetic control group. These kinetic
      changes are identical to those observed in Type I diabetic nephropathy patients.
      There are similar underlying changes in the erythrocyte plasma membrane with the
      development of nephropathy in both Type I and Type II diabetes.

PMID- 8151604
TI  - Physical activity, hypertension and risk of heart attack in men without evidence
      of ischaemic heart disease.
AB  - The role of hypertension in the increased rate of heart attack reported in
      vigorously active subjects was examined in a large prospective study of 7735
      middle-aged men drawn from general practices in 24 British towns (The British
      Regional Heart Study). Analyses were restricted to 5694 men with no evidence of
      pre-existing ischaemic heart disease or stroke at screening, in whom there were
      311 major ischaemic heart disease events after 9.5 years follow-up. Risk of major
      ischaemic heart disease events decreased significantly with increasing physical
      activity to levels of moderate/moderately vigorous activity, with a 50% reduction
      in risk compared with inactive men after adjustment for age, body mass index,
      smoking, heavy drinking, social class and blood cholesterol. However, at the
      highest level of physical activity (vigorous group) risk of major ischaemic heart
      disease events was increased above that seen in the moderate/moderately vigorous
      group (rr = 1.68, P = 0.05). When separated into normotensives (n = 3888) and
      hypertensives (n = 1806; SBP > or = 160 mmHg or DBP > or = 90 mmHg or on regular
      antihypertensive treatment), the increased risk of major ischaemic heart disease
      events in the vigorous group was only evident in hypertensive men. They showed
      more than a twofold increase in risk compared with the moderate and moderately
      vigorous group (rr = 2.7, P < 0.05). In normotensive men, risk was significantly
      lowered in those engaged in moderate activity with no further decline in rate of
      heart attack at increasing levels of physical activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8151605
TI  - Intracellular and extracellular antioxidant buffering levels in erythrocytes from
      pregnancy-induced hypertension.
AB  - Both intracellular (lysate thiol, lysate glutathione and lysate superoxide
      dismutase) and extracellular (plasma thiol, plasma glutathione and membrane
      thiol) antioxidant buffering levels were measured in red blood cells from
      patients with pregnancy-induced hypertension (PIH). We found the following. (1)
      The levels of plasma thiol and plasma glutathione in PIH women with proteinuria
      were markedly lower than that in the normal pregnancy. (2) The concentrations of
      lysate glutathione and superoxide dismutase in PIH women with proteinuria were
      significantly decreased compared with that in the normal pregnancy. (3) With the
      exception of plasma and lysate glutathione, all the tested antioxidant markers
      were not significantly different between PIH women without proteinuria and normal
      pregnancy. (4) There was no statistical correlation between antioxidant buffering
      level and BP in patients with PIH. We concluded that both extracellular and
      intracellular antioxidant buffering levels were decreased in patients with PIH,
      especially in those with proteinuria. The reduction of the antioxidant buffering
      level could account for several important pathophysiological features of PIH,
      such as the elevation of intracellular calcium, decreased red blood cell
      deformability and endothelial damage.

PMID- 8151606
TI  - Effect of sodium restriction and fish oil supplementation on BP and thrombotic
      risk factors in patients treated with ACE inhibitors.
AB  - Effects of dietary sodium restriction combined with fish oil supplementation on
      BP and related risk factors were assessed in hypertensives treated with
      angiotensin converting enzyme (ACE) inhibitors. After a four week run-in phase, a
      six week intervention trial was conducted in which four matched groups of 14
      patients, taking either captopril or enalapril, were assigned to one of four
      dietary treatments: low sodium (80 mmol/day) with fish oil (5 g of omega-3 fatty
      acids per day); normal sodium (150 mmol/day) with fish oil; low sodium with olive
      oil; normal sodium with olive oil. All subjects adopted a low sodium diet and
      adjustments of nutrient intake were made by double-blind administration of sodium
      and oils in supplementary tablets and capsules. BP fell in all treatment groups
      during intervention. However, the reduction of SBP was 4.2 mmHg greater in
      subjects on a low sodium intake than in those taking normal sodium. There were no
      differences in BP between those taking olive oil and those taking fish oil but
      plasma triglycerides and serum thromboxane production were reduced by 27% and
      51%, respectively in the latter. Thus the antihypertensive effect of ACE
      inhibitors can be augmented by sodium restriction alone but supplementing the
      diet with fish oil may yield additional cardiovascular benefits.

PMID- 8151607
TI  - Alteration of coronary perfusion reserve in hypertensive patients with diabetes.
AB  - This investigation was performed to determine whether diabetes mellitus has an
      additive effect on diminishing coronary perfusion reserve index in hypertensive
      patients. Coronary perfusion reserve index, thallium lung uptake, the
      electrocardiogram and haemodynamic parameters were evaluated by exercise thallium
      myocardial perfusion scintigraphy. In 18% of hypertensive and 13% of diabetic
      hypertensive patients there was evidence of left ventricular hypertrophy on
      electrocardiogram. The maximum heart rate achieved in hypertensive, diabetic and
      diabetic-hypertensive patients was significantly lower (P < 0.05) than in control
      patients. The maximum SBP achieved in hypertensive (210 +/- 40 mmHg) and diabetic
      hypertensive patients (216 +/- 36 mmHg) was higher (P < 0.05) than in control
      patients (186 +/- 32 mmHg). A significantly higher number of diabetic patients
      (53%) did not achieve the exercise rate pressure product of > 26,000 when
      compared with control (27%), hypertensive (24%) and diabetic-hypertensive (30%)
      patients. Coronary perfusion reserve index in hypertensive patients decreased
      significantly (P < 0.05) when compared with control (no hypertension, no
      diabetes) patients (1.67 +/- .14 vs. 1.79 +/- .17). Coronary vasodilatory reserve
      index was also reduced significantly (P < 0.05) in diabetic patients in
      comparison with controls (1.66 +/- .17 vs. 1.79 +/- .17), and was further reduced
      in diabetic-hypertensive patients when compared with control patients (1.63 +/-
      .13 vs. 1.79 +/- .17). Thallium uptake in the lung quantified as thallium lung to
      heart ratio were comparable in all four groups. The results suggest that diabetes
      mellitus diminishes the coronary perfusion reserve index in patients with
      hypertension and therefore many account for the increased cardiovascular
      morbidity in these patients.

PMID- 8151608
TI  - Ketanserin's sympatholytic and serotonin2-receptor blocking actions precede the
      hypotensive effects.
AB  - The hypotensive action of ketanserin in humans remains incompletely defined but
      may be mediated by factors unrelated to vascular alpha 1 or serotonin2-receptor
      blockade. We examined the effects of ketanserin on indices of sympathetic drive,
      alpha 1- and serotonin2-receptor responses, and sympathetic tone in 13 elderly
      men with mild hypertension. Studies were performed after ten days and six weeks
      of double-blind assignment to placebo and ketanserin 40 mg twice daily. An eight
      week long single-blind, placebo washout period separated the double-blind phases.
      In the entire group, ketanserin lowered BP and heart rate significantly after six
      weeks but not at ten days. In contrast, plasma noradrenaline, an index of
      sympathetic drive, and platelet aggregation in response to 1 microM serotonin, an
      index of serotonin2-receptor antagonism, declined significantly after both ten
      days and six weeks (P < 0.05) on ketanserin versus placebo. Mean BP after six
      weeks on ketanserin fell to > 10% in seven patients (responders) and to < 10% in
      six subjects (nonresponders). Responders had higher baseline SBPs and heart rates
      compared with nonresponders. Even in responders, BP was reduced at six weeks but
      not after ten days on ketanserin versus placebo. Plasma and platelet
      noradrenaline, plasma renin activity, and platelet responses to serotonin at
      baseline and during ketanserin did not distinguish between responders and
      nonresponders. Ketanserin reduces sympathetic drive and antagonizes serotonin2
      receptors in the short term. The relationship of these actions to the hypotensive
      effect of ketanserin, which is delayed and dependent on the initial BP, is
      unclear.

PMID- 8151609
TI  - Double-blind comparison of amlodipine and nifedipine retard in the treatment of
      mild to moderate hypertension.
AB  - The efficacy and safety profiles of amlodipine (5-10 mg once daily) and
      nifedipine retard (20-40 mg twice daily) were compared in 111 hypertensive
      patients (sitting DBP in 95-115 mmHg) during eight weeks of treatment in a
      randomised double-blind parallel group study. BP was measured 22-24 hours after
      the daily dose of amlodipine and 10-12 hours after a dose of nifedipine retard.
      Baseline sitting BPs of 175/105 mmHg and 168/104 mmHg were significantly reduced
      (P < 0.05) to 157/93 mmHg and 151/92 mmHg at the end of treatment in response to
      mean daily doses of amlodipine 7.3 mg and nifedipine retard 58.9 mg. There were
      no clinically significant changes in heart rate with either treatment. Three
      patients in the amlodipine group and five patients in the nifedipine retard group
      could not be considered in analysis. The total numbers of adverse events
      (considered related or possibly related to treatment) (42 vs. 36) as well as the
      numbers of patients experiencing such events (22 vs. 22) were similar in the
      amlodipine and nifedipine retard treated groups, respectively, but with a greater
      incidence of headaches in response to nifedipine retard and of oedema in response
      to amlodipine. Five patients in each treatment group discontinued therapy due to
      such events. Overall the results showed once daily amlodipine as equivalent to
      twice daily nifedipine retard in the management of mild to moderate hypertension.

PMID- 8151610
TI  - Phaeochromocytoma revealed by type A acute aortic dissection.

PMID- 8151611
TI  - Influence of acute stress (missile attacks on civilian population) on blood
      pressure, measured with ambulatory monitoring.

PMID- 8151612
TI  - Dianilinophthalimides: potent and selective, ATP-competitive inhibitors of the
      EGF-receptor protein tyrosine kinase.
AB  - Dianilinophthalimides represent a novel class of inhibitors of the EGF-receptor
      protein tyrosine kinase with a high degree of selectivity versus other tyrosine
      and serine/threonine kinases. Steady-state kinetic analysis of compound 3, which
      showed potent inhibitory activity, revealed competitive type kinetics relative to
      ATP. Despite a highly symmetrical structure of compound 3, X-ray studies revealed
      an unsymmetrical propeller-shaped conformation of the molecule which differs
      clearly from that of the constitutionally related staurosporine aglycons. These
      conformational differences may explain the reversal of the selectivity profile of
      compound 3 relative to the staurosporine aglycons. In cellular assays compounds 3
      and 4 have been shown to inhibit EGF-induced receptor autophosphorylation, c-fos
      induction and EGF-dependent proliferation of Balb/c MK cells. This inhibition was
      selective as compounds had no effect on PDGF-induced receptor autophosphorylation
      and c-fos induction. Furthermore, compound 3 showed potent antitumor activity in
      vivo at well-tolerated doses.

PMID- 8151613
TI  - 6H-pyrazolo[4,5,1-de]acridin-6-ones as a novel class of antitumor agents.
      Synthesis and biological activity.
AB  - The 7-substituted 6H-pyrazolo[4,5,1-de]acridin-6-ones with (aminoalkyl)amino
      and/or (hydroxyalkyl)amino groups in the side chains were synthesized by
      bromination using N-bromosuccinimide and the subsequent reaction with amines from
      the 7-substituted 5-bromo-2-methyl-6H-pyrazolo-[4,5,1-de]acridin-6-one. The
      substitution reaction of the amines with alkyl bromide (the C2 position) and aryl
      bromide (the C5 position) was accomplished by choosing the proper reaction
      conditions. These compounds show DNA intercalating ability in ethidium
      fluorescence assay and antiproliferative activity against Hela S3 cells.
      Impressive antitumor activity in vivo against murine P388 leukemia and murine
      sarcoma 180 solid tumor in mice was demonstrated for the 7-hydroxy analogs. In
      addition, some of these showed excellent antitumor activity against adriamycin
      resistant murine P388 leukemia (P388/ADM) in mice.

PMID- 8151614
TI  - Specific inhibitors of ileal bile acid transport.

PMID- 8151615
TI  - A new orally active insulin-mimetic vanadyl complex: bis(pyrrolidine-N
      carbodithioato)oxovanadium (IV).

PMID- 8151616
TI  - A novel 3-substituted benzazepinone growth hormone secretagogue (L-692,429).
AB  - The 3-substituted benzazepinone, L-692,429 (compound 1), is the prototype
      compound of a novel class of compounds that stimulate release of growth hormone
      (GH). The molecule evolved from efforts to identify a non-peptide mimic of the
      growth hormone-releasing hexapeptide, GHRP-6. Compound 1 is prepared by
      sequential attachment of dimethyl-beta-alanine and 2'-biphenylyltetrazole side
      chains to a chiral 3-aminobenzolactam nucleus. Comparison of the biological
      activity of 1 with the corresponding six- and eight-membered lactam analogs shows
      the seven-membered benzazepinone skeleton to be preferred. Molecular modeling of
      the structurally diverse GH secretagogues, L-692,429 and GHRP-6, was performed.

PMID- 8151617
TI  - Synthesis of selective non-Ca(2+)-mobilizing inhibitors of D-myo-inositol 1,4,5
      trisphosphate 5-phosphatase.
AB  - Syntheses of novel phosphorothioate-based non-Ca(2+)-releasing inhibitors of myo
      inositol 1,4,5-trisphosphate 5-phosphatase are described. 1L-myo-Inositol 1,4,5
      trisphosphorothioate, myo-inositol 1,3,5-trisphosphorothioate, and 1L-chiro
      inositol 1,4,6-trisphosphorothioate have been synthesized from 1L-2,3,6-tri-O
      benzyl-1-O-(cis-prop-1-enyl)-myo-inositol, 2,4,6-tris-O-(p-methoxybenzyl)-myo
      inositol orthoformate and 1L-2,3,5-tri-O-benzyl-chiro-inositol, respectively. 1L
      2,3,5-Tri-O-benzyl-chiro-inositol was also used to prepare 1L-chiro-inositol
      1,4,6-trisphosphate. The phosphorothioates did not mobilize intracellular Ca2+
      but were highly potent inhibitors of Ins(1,4,5)P3 5-phosphatase, and myo-inositol
      1,3,5-trisphosphorothioate and 1L-chiro-inositol 1,4,6-trisphosphorothioate were
      selective for this enzyme.

PMID- 8151618
TI  - Benzoxazolamines and benzothiazolamines: potent, enantioselective inhibitors of
      leukotriene biosynthesis with a novel mechanism of action.
AB  - A series of benzoxazolamine and benzothiazolamine analogs that inhibit
      leukotriene (LT) biosynthesis are described. The initial lead, (S)-N
      (benzothiazol-2- yl)phenylalanine ethyl ester (5a), was discovered in a screening
      program for inhibition of Ca-ionophore-A23187-induced LTB4 release in human
      polymorphonuclear leukocytes (IC50 0.23 microM). Through structural modification,
      it was determined that hydrophobic substituents in the 5-position and replacement
      of the phenyl ring of phenylalanine with a cyclohexyl group greatly enhance
      potency. Several ester bioisosteres that retain potency and enantiomeric
      selectivity are described. Lead optimization culminated in (S)-N-[2-cyclohexyl-1
      (2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (43b), IC50 0.001 microM. The
      compounds described are not inhibitors of 5-lipoxygenase but, rather, act at the
      level of arachidonic acid release.

PMID- 8151619
TI  - Iron(III)-chelating resins. IX. Antibacterial activity of a water-insoluble
      iron(III)-chelating resin.
AB  - Antibacterial activity of a water-insoluble iron(III)-chelating resin with
      covalently bonded 3-hydroxy-2-methyl-4(1H)-pyridinone (HMP) groups was evaluated
      in a brain heart infusion (BHI) medium. The activity of the resin against
      Escherichia coli was lower than that of soluble HMP iron(III) chelators, whereas
      against Listeria inocua, an activity approximately equal to those of the soluble
      chelators was found. It was observed that the growth of E. coli and L. inocua was
      reduced by increasing the amounts of the resin from 2 to 40 mg of resin/mL of
      medium. Inhibition of bacterial growth in the presence of the resin (10 mg/mL)
      was abolished by addition of ferric ion to the medium, indicating that the growth
      of E. coli and L. inocua was dependent on the available iron in the medium.
      Reducing the iron concentration in the medium from 14.2 to 0.16 microM (by action
      of the resin) resulted in a decrease in the growth response from 100% to 19% for
      E. coli and from 100% to 10% for L. inocua. In addition, the influence of citrate
      was studied, but only small effects of citrate supplementation on the growth of
      bacteria and on the antibacterial activity of the resin were observed.

PMID- 8151620
TI  - Homodimeric and heterodimeric bis(amino thiol) oxometal complexes with rhenium(V)
      and technetium(V). Control of heterodimeric complex formation and an approach to
      metal complexes that mimic steroid hormones.
AB  - We have investigated the possibility of preparing complexes of rhenium and
      technetium whose shape resembles that of ligands for steroid receptors. The
      general structure of N2S2 complexes of oxorhenium(V) and oxotechnetium(V) is such
      that they could replace the BC ring system of steroid, thereby generating a metal
      complex system with considerable size and shape similarity to a steroid. Such a
      metal-integrated steroid-shaped complex can be constructed as a heterodimer of
      two different amino thiols; complexes of rhenium and technetium with such
      heterodimeric bis-bidentate structure have not been systematically studied. In
      this investigation, we have shown that complexes of this nature form readily when
      appropriate metal precursors are combined with a mixture of amino thiols. In the
      systems we have studied, heterodimeric complex formation is preferred over
      homodimeric complex formation, and in one system where we were able to obtain an
      X-ray crystal structure, this oxorhenium heterodimer had the desired trans
      geometry. These rhenium and technetium-99m complexes are reasonably stable toward
      ligand exchange; they can be readily purified by chromatography under appropriate
      conditions, and the one technetium-99m complex studied in vivo shows some
      persistence in blood and gives good initial uptake in several tissues. The
      convenient and selective formation of such bis-bidentate heterodimeric complexes
      suggests that the development of metal-integrated complexes that resemble ligands
      for receptors may be possible.

PMID- 8151621
TI  - Novel 4-(aryloxy)tetrahydropyridine analogs of MPTP as monoamine oxidase A and B
      substrates.
AB  - The exceptionally good monoamine oxidase (MAO) substrate properties of several 4
      (arylmethyl)-1-methyl-1,2,3,6-tetrahydropyridine derivatives related to the
      neurotoxin MPTP have prompted studies to evaluate the corresponding properties of
      tetrahydropyridine derivatives bearing heteroatom-linked groups at C-4. The
      expected dihydropyridinium metabolites generated from these MAO-A- and MAO-B
      catalyzed oxidations of the 4-(aryloxy)tetrahydropyridine analogs were found to
      undergo rapid hydrolytic cleavage to yield the corresponding arenol and 1-methyl
      2,3-dihydro-4-pyridone, a species that could be monitored spectrophotometrically.
      We have exploited this reaction sequence to probe the active sites of beef liver
      MAO-B and human placental MAO-A with a variety of 4-(aryloxy)-1-methyl-1,2,3,6
      tetrahydropyridine derivatives. The results are discussed in relationship to
      recently published reports describing the MAO-A vs MAO-B selectivity of various 4
      (arylmethyl)tetrahydropyridine derivatives.

PMID- 8151622
TI  - Development of a receptor-interaction model for serotonin 5-HT2 receptor
      antagonists. Predicting selectivity with respect to dopamine D2 receptors.
AB  - A receptor-interaction model for serotonin 5-HT2 receptor antagonists has been
      developed by conformational analysis with molecular mechanics (MM2(91)) and
      superimposition studies of serotonin 5-HT2 receptor antagonists. Substituted 3-(4
      piperidinyl)-,1-(4- piperidinyl)-,3-(1,2,3,6-tetrahydropyridin-4-yl)-, and 1
      (1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles, substituted 3-(4-fluorophenyl)-1-(4
      piperazinyl)indans, cyprohepatadine derivatives, ritanserin, and danitracene have
      been used as bases for the model. Other serotonin 5-HT2 receptor antagonists,
      such as ketanserin and MDL 11,939, are well accommodated into the model.
      Comparison of the model with a recently described receptor-interaction model for
      dopamine D2 receptor antagonists suggests a common pharmacophore for dopamine D2
      and serotonin 5-HT2 receptor antagonists. Important steric differences between 5
      HT2 receptor antagonists with additional high affinity for dopamine D2 receptors
      and serotonin 5-HT2 receptor antagonists with high selectivity versus D2
      receptors are described. The geometry of the receptor-interaction model described
      is significantly different from that of a recently reported receptor-interaction
      model for 5-HT2 receptor agonists and antagonists developed by use of (+)-LSD as
      a template, suggesting the existence of two binding modes at the 5-HT2 receptor.

PMID- 8151623
TI  - The use of the GRID program in the 3-D QSAR analysis of a series of calcium
      channel agonists.
AB  - The use of GRID in the 3-D QSAR analysis of a series of calcium-channel agonists
      is described. Partial least-squares analysis of GRID maps showing the interaction
      energy between an alkyl hydroxyl probe and a series of agonists in 3-D space
      generated a predictive quantitative model of the variation of biological
      activity. The macroscopic descriptors CLOGP and CMR were included in the
      analysis, and the importance of appropriate block scaling is highlighted. The
      discussion highlights the interpretation of the resulting regression maps, and
      the steric, electrostatic, lipophilic, and hydrogen-bonding preferences of the
      calcium-channel receptor are identified.

PMID- 8151624
TI  - A nonlinear map of substituent constants for selecting test series and deriving
      structure-activity relationships. 1. Aromatic series.
AB  - A nonlinear mapping (NLM) analysis was performed on a set of 166 aromatic
      substituents described by six variables encoding hydrophobic (pi), steric (MR),
      and electronic effects (HBA, HBD, F, and R). NLM allowed to easily summarize the
      main information contained in the original data table. By means of collections of
      graphs, it was possible to relate the structure of the substituents to their pi,
      MR, HBA, HBD, F, and R values. The proposed approach provides a useful and easy
      tool for the selection of test series and for deriving structure-activity
      relationships.

PMID- 8151625
TI  - A nonlinear map of substituent constants for selecting test series and deriving
      structure-activity relationships. 2. Aliphatic series.
AB  - A nonlinear mapping (NLM) analysis was performed on a set of 103 aliphatic
      substituents described by five variables encoding hydrophobic (Fr), steric (MR),
      and electronic effects (HBA, HBD, and F). NLM allowed to easily summarize the
      main information contained in the original data table. By means of collections of
      graphs, it was possible to relate the structure of the aliphatic substituents to
      their Fr, MR, HBA, HBD, and F values. The proposed approach provides a useful and
      easy tool for the selection of test series and for deriving structure-activity
      relationships.

PMID- 8151626
TI  - Antiinflammatory 4,5-diarylpyrroles: synthesis and QSAR.
AB  - A series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4
      (methylsulfonyl)phenyl]-1H- pyrroles was synthesized and found to be active in
      the rat adjuvant arthritis model of inflammation. The most active compounds were
      the 2-halo derivatives in the order of chloro > bromo > iodo. The same pattern of
      activity was observed for the 2,3-dihalopyrroles. Quantitative structure-activity
      relationship studies suggested that the activity could be correlated with the
      molar refractivity and the inductive field effect of the 2-substituent and the
      lipophilicity of the 3-substituent.

PMID- 8151627
TI  - Toxic effects of fatty acid anilides on the oxygen defense systems of guinea pig
      lungs and erythrocytes.
AB  - Toxic oil syndrome (TOS) is caused by ingestion of denatured edible oils. Even
      though the etiology and pathogenesis of this disease are not fully known, it is
      quite clear that generation of free radicals caused by ingestion of fatty acid
      anilides is responsible for the pathogenetic mechanism in many TOS patients.
      Fatty acid anilides may also alter the free radical status of lungs and
      erythrocytes; this possibility may shed some light on understanding toxic oil
      syndrome. The present study describes the effects of oral administration of fatty
      acid anilides on the activities of major enzymes involved in the oxygen defense
      systems of lungs and erythrocytes. Feeding fatty acid anilides caused an increase
      in the superoxide dismutase (SOD) activity in erythrocytes, whereas it caused a
      decrease in the SOD activity in lungs. GSH-Px activity was not significantly
      changed in erythrocytes but was decreased in lungs. Although the activity of
      catalase was increased only by a higher dose in the erythrocytes, it was not
      affected in the lung at any dosage. Even though the ingestion of fatty acid
      anilides caused an increase in the SOD activity in the erythrocytes and a
      decrease in the SOD activity in the lungs, there was an increase in the lipid
      peroxidation in both cases. The increase in lipid peroxidation in erythrocytes is
      probably caused by the accumulation of H2O2, and that in the lungs is due to the
      accumulation of superoxide anion.

PMID- 8151628
TI  - Aluminum alters calcium transport in plasma membrane and endoplasmic reticulum
      from rat brain.
AB  - Calcium is actively transported into intracellular organelles and out of the
      cytoplasm by Ca2+/Mg(2+)-ATPases located in the endoplasmic reticulum and plasma
      membranes. We studied the effects of aluminum on calcium transport in the adult
      rat brain. We examined 45Ca-uptake in microsomes and Ca(2+)-ATPase activity in
      microsomes and synaptosomes isolated from the frontal cortex and cerebellum of
      adult male Long-Evans rats. ATP-dependent 45Ca-uptake was similar in microsomes
      from both brain regions. The addition of 50-800 microM AlCl3 resulted in a
      concentration-dependent inhibition of 45Ca-uptake. Mg(2+)-dependent Ca(2+)-ATPase
      activity was significantly lower in synaptosomes compared to microsomes in both
      frontal cortex and cerebellum. In contrast to the uptake studies, AlCl3
      stimulated Mg(2+)-dependent Ca(2+)-ATPase activity in both microsomes and
      synaptosomes from both brain regions. To determine the relationship between
      aluminum and Mg2+, we measured ATPase activity in the presence of increasing
      concentrations of Mg2+ or AlCl3. Maximal ATPase activity was obtained between 3
      and 6 mM Mg2+. When we substituted AlCl3 for Mg2+, ATPase activity was also
      stimulated in a concentration-dependent manner, but to a greater extent than with
      Mg2+. One interpretation of these data is that aluminum acts at multiple sites to
      displace both Mg2+ and Ca2+, increasing the activity of the Ca(2+)-ATPase, but
      disrupting transport of calcium.

PMID- 8151629
TI  - Controversial role of intracellular iron in the mechanisms of chemically-induced
      hepatotoxicity.
AB  - Hepatotoxicity induced by various therapeutic agents, industrial chemicals and
      environmental pollutants is a well-recognized phenomenon. These chemicals are
      known to cause liver damage that is localized to either periportal or
      centrilobular regions of the liver lobule (1-3). Depending on dose, duration, and
      route of exposure, the resultant liver injury may regress or progress and becomes
      irreversible (1). Mechanisms involved in this selective, localized toxicity have
      been the target of extensive research efforts, and many studies produced
      conflicting results. As depicted in Figure 1, although many investigators
      implicate iron and lipid peroxidation in this process (4-9), others dispute such
      assertions (10-12).

PMID- 8151630
TI  - Effects of P450 inhibition and induction on the olfactory toxicity of beta,beta'
      iminodipropionitrile (IDPN) in the rat.
AB  - In addition to the neurotoxic effects of beta,beta'-iminodipropionitrile (IDPN)
      which have been previously reported by other investigators, the olfactory
      toxicity of this compound has recently been uncovered in this laboratory. Due to
      the apparently conflicting observations that the IDPN-induced lesion in the
      olfactory mucosa is very focal in nature (suggesting site-specific activation)
      and the observation by other investigators that the behavioral effects of IDPN
      appear to be due to the parent compound, we initiated studies into the possible
      role of the cytochrome P450 enzymes in the olfactory toxicity of IDPN.
      Immunohistochemical studies with antibodies raised against several different P450
      isoforms revealed good correlation between IDPN-induced olfactory mucosal
      degeneration and the localization of a protein immunoreacting with an antibody to
      P450 2E1. Enzymatic studies revealed that there is approximately five-fold more p
      nitrophenol hydroxylation activity in the olfactory mucosa than in the liver on a
      per milligram microsomal protein basis. Administration of 1% acetone in the
      drinking water increased the levels of olfactory mucosal 2E1, and the increase in
      enzyme levels corresponded to increased olfactory toxicity of IDPN; inhibition of
      P450 activities with either metyrapone or carbon tetrachloride eliminated or
      significantly decreased the olfactory toxicity of IDPN, respectively. These
      studies suggest a role for cytochrome P450, specifically the 2E1 isoform, in the
      activation of IDPN within the nasal mucosa.

PMID- 8151631
TI  - Development of pancellular toxicity in guinea pig lung by ingestion of
      oleylanilide.
AB  - Toxic oil syndrome (TOS), characterized by widespread thromboembolism,
      vasculotoxicity, and ARDS, develops in humans ingesting denatured edible oils.
      The mechanism(s) involved in targeted vasculocentric damage in this multi-system
      disorder is not known. Oleylanilide (OA) was synthesized and fed to male, young
      adult guinea pigs by gavage for 30 days at doses of 35, 50, and 100 mg/kg/day in
      groups of six animals each respective to weight. Controls were fed olive oil.
      Oleylanilide fed animals gained less weight than controls. At the end of
      experiment, right lungs were inflation fixed in appropriate fixative for
      histology and transmission electron microscopy (TEM) and left lungs were frozen
      at -70 degrees C for biochemical analyses. The activity of glycerophosphate
      acyltransferase (GAT) and cholinephosphotransferase (CPT), two key enzymes
      involved in phospholipid biosynthesis, were decreased in lung due to OA
      ingestion. All doses of OA induced marked perivascular and peribronchoiolar
      monocytic infiltrates that often formed prominent nodules; segmental vascular
      smooth muscle cell proliferation and derangement of myocytic polarity,
      subendothelial foamy infiltrates, and edema; nuclear pyknosis and dropout in
      vascular and bronchial targetoid myocytes; and denudation of bronchiolar
      epithelial cells. Alveoli contained large numbers of monocytes, macrophages, red
      cells, edema, and debris. Transmission electron microscopy showed type I cell
      cytoplasmic ballooning and disintegration of type I cell; contracted and blebbed
      endothelial cells, fibrin thrombi in capillaries, intracellular megalamellar
      bodies in type II cells, and surfactant lamellae; and liposomes and fine granular
      precipitates within alveoli, and contraction and lift off of bronchiolar
      epithelial cells. Monocytes, mast cells, and eosinophils infiltrated bronchial
      walls. Furthermore, there was deposition of electron dense particles on the
      surface of the alveolar wall.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8151632
TI  - Cytosolic 5'-nucleotidase/nucleoside phosphotransferase: a nucleoside analog
      activating enzyme?
AB  - Nucleoside phosphotransferase acting on inosine and deoxyinosine has been
      partially purified from cultured Chinese hamster lung fibroblasts (V79). The
      activity is associated with a cytosolic 5'-nucleotidase acting on IMP and
      deoxyIMP. The transfer of the phosphate group from IMP to inosine catalyzed by
      this enzyme was activated by ATP and 2,3-bisphosphoglycerate. Inosine,
      deoxyinosine, guanosine, deoxyguanosine, and the nucleoside analogs 2',3'
      dideoxyinosine and 8-azaguanosine are substrates, while adenosine and
      deoxyadenosine are not. IMP, deoxyIMP, GMP, and deoxyGMP are the best phosphate
      donors. The cytosolic 5'-nucleotidase/phosphotransferase substrate, 8
      azaguanosine, was found to be very toxic for cultured fibroblasts (LD50 = 0.32
      microM). Mutants resistant to either 8-azaguanosine and the correspondent base 8
      azaguanine were isolated and characterized. Our results indicated that the 8
      azaguanosine-resistant cells were lacking both cytosolic 5'-nucleotidase and
      hypoxanthine-guanine phosphoribosyltransferase, while 8-azaguanine resistant
      cells were lacking only the latter enzyme. Despite this observation, both mutants
      displayed 8-azaguanosine resistance, thus indicating that cytosolic 5'
      nucleotidase is not essential for the activation of this nucleoside analog.

PMID- 8151634
TI  - French myotonic dystrophy families show expansion of a CTG repeat in complete
      linkage disequilibrium with an intragenic 1 kb insertion.
AB  - The molecular basis of myotonic dystrophy (DM) has been characterised. All DM
      mutations characterised to date appear as an unstable elongation of a fragment
      containing a tandem repeat of a CTG motif, which can be visualised in both EcoRI
      and BamHI digests. It has been shown that the fragment is polymorphic in the
      normal population. Another 1 kb insertion/deletion polymorphism located near the
      unstable CTG repeat region has been identified. The 1 kb insertion allele is
      present in all DM patients. These different polymorphic systems can be
      distinguished using cDNA25 and BamHI, because this enzyme cuts between the site
      of the 1 kb insertion and the CTG repeat. We thus haplotyped DM patients from 72
      French families and clearly showed that all chromosomes (100%) with the DM
      mutation carried the 1 kb insertion as well. In addition to this association, we
      detected significant linkage disequilibrium between the DM locus and D19S63 for
      which allelic frequencies were different from other European populations. Our
      results in the French DM population are thus in agreement with the hypothesis
      that the CTG expansion occurred on one or a few ancestral chromosomes carrying
      the large 1 kb insertion allele.

PMID- 8151633
TI  - Mouse homologues of human hereditary disease.
AB  - Details are given of 214 loci known to be associated with human hereditary
      disease, which have been mapped on both human and mouse chromosomes. Forty two of
      these have pathological variants in both species; in general the mouse variants
      are similar in their effects to the corresponding human ones, but exceptions
      include the Dmd/DMD and Hprt/HPRT mutations which cause little, if any, harm in
      mice. Possible reasons for phenotypic differences are discussed. In most
      pathological variants the gene product seems to be absent or greatly reduced in
      both species. The extensive data on conserved segments between human and mouse
      chromosomes are used to predict locations in the mouse of over 50 loci of medical
      interest which are mapped so far only on human chromosomes. In about 80% of these
      a fairly confident prediction can be made. Some likely homologies between mapped
      mouse loci and unmapped human ones are also given. Sixty six human and mouse
      proto-oncogene and growth factor gene homologies are also listed; those of
      confirmed location are all in known conserved segments. A survey of 18 mapped
      human disease loci and chromosome regions in which the manifestation or severity
      of pathological effects is thought to be the result of genomic imprinting shows
      that most of the homologous regions in the mouse are also associated with
      imprinting, especially those with homologues on human chromosomes 11p and 15q.
      Useful methods of accelerating the production of mouse models of human hereditary
      disease include (1) use of a supermutagen, such as ethylnitrosourea (ENU), (2)
      targeted mutagenesis involving ES cells, and (3) use of gene transfer techniques,
      with production of 'knockout mutations'.

PMID- 8151635
TI  - Absence of myotonic dystrophy in southern African Negroids is associated with a
      significantly lower number of CTG trinucleotide repeats.
AB  - Myotonic dystrophy (DM) is associated with an increased number of CTG repeats in
      the 3' untranslated region of the myotonin gene. Because DM has not been observed
      in southern African Negroids, a study of the CTG repeat polymorphism in this
      population was undertake. A total of 210 unrelated subjects was studied by PCR
      analysis of the trinucleotide repeat in the DM gene and the size and distribution
      of the CTG repeat were determined. The alleles ranged in length from five to 22
      repeats. A previously undescribed BglI polymorphism was found which could lead to
      erroneous diagnosis of DM in people from this population. South African Negroids
      were found to have significantly fewer large repeat lengths than do white and
      Japanese populations. It is suggested that the occurrence of fewer large CTG
      repeats in the normal range may, in part, explain the absence of DM in southern
      African Negroids.

PMID- 8151636
TI  - Comparison of the relative levels of the 3243 (A-->G) mtDNA mutation in
      heteroplasmic adult and fetal tissues.
AB  - In this report, levels of the 3243 A to G mtDNA mutation associated with the
      mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
      syndrome were measured in different heteroplasmic tissues of subjects in a
      kindred including adults with variable clinical phenotypes and a fetus. The
      relative proportions of mutant mtDNA varied widely (0.03 to 0.67) between
      identical tissues of the six different subjects and between different tissues of
      the same subjects. In the one adult for whom sufficient data were available there
      was an apparent correlation between the distribution of mutant mtDNA and clinical
      presentation. A woman without neurological symptoms who died prematurely with a
      cardiomyopathy and lactic acidosis had higher proportions of mutant in heart
      (0.49, SD 0.02), skeletal muscle (0.56, SD 0.01), and liver (0.55, SD 0.12) than
      in other tissues studied (for example, kidney, 0.03, SD 0.01). A strikingly
      different result was found in a 24 week old fetus in whom there was little
      variation in heteroplasmy in different tissues (average proportion of mutant
      mtDNA in six tissues, 0.53, SD 0.02). These observations add cardiomyopathy to
      the growing list of presenting features of the 3243 mtDNA mutation. The unique
      results from the fetus suggest also that selection pressures acting on either
      wild type or 3243 mutant mtDNA (rather than variation from replicative
      segregation of the heteroplasmic mtDNA) may be responsible primarily for the
      variable levels of 3243 mutant mtDNA in different heteroplasmic tissues of
      adults.

PMID- 8151637
TI  - Juvenile Kearns-Sayre syndrome initially misdiagnosed as a psychosomatic
      disorder.
AB  - We have investigated a 15 year old girl with progressive external
      ophthalmoplegia, including bilateral ptosis and retinal rod and cone cell
      dysfunction with atypical retinal pigmentation, complicated by cerebellar ataxia,
      partial cardiac conduction block, and diabetes mellitus. In infancy she had a
      severe crisis of bone marrow depression, and as a child she suffered from
      hypersensitivity to light, increasing fatigue, and vertigo, signs that were
      initially though to be psychosomatic. Histological examination showed
      mitochondrial myopathy, and subsequent mitochondrial DNA (mtDNA) analysis showed
      a deletion of approximately 5500 base pairs in 35 to 40% of her muscle mtDNA. We
      therefore conclude that this patient has developed the Kearns-Sayre syndrome
      after a Pearson syndrome-like crisis in her first year of life.

PMID- 8151638
TI  - Ascertainment and severity of Marfan syndrome in a Scottish population.
AB  - This study in north east Scotland has shown that Marfan syndrome has a minimal
      birth incidence of 1:9802 live births, a minimal prevalence of 1:14217, and that
      8/30 (26.7%) of cases in our series are new mutations. The calculated mutation
      rate is 15 +/- 6.7 x 10(-6) and there is evidence of reduced reproductive
      fitness.

PMID- 8151639
TI  - Genetic heterogeneity of congenital hypertrophy of the retinal pigment epithelium
      (CHRPE) in families with familial adenomatous polyposis.
AB  - One hundred and eighteen subjects with familial adenomatous polyposis (FAP) and
      80 of their relatives who were at low risk (< 0.01) of carrying the FAP gene were
      scored by one of us (BJ) or by colleagues to assess the frequency of congenital
      hypertrophy of the retinal pigment epithelium (CHRPE). A CHRPE is defined as an
      "oval pigmented lesion surrounded by depigmented halo". Seventy five (63.6%) of
      the FAP cases and one (1.2%) of their relatives had at least one CHRPE. There was
      no systematic difference in the number of CHRPEs in the left and right eyes so
      all analyses are based on total number of CHRPEs and the findings were highly
      correlated (p = 0.001 for a test of no correlation). There was also no evidence
      of any age effect in total number of CHRPEs in affected subjects. In 26 families
      there was more than one subject affected with FAP. There was a significant common
      family effect with respect to CHRPE expression for total number of CHRPEs with an
      F statistic of 1.73 (p = 0.02 for a test of no family aggregation) indicating
      that family members are more similar to each other than to affected subjects from
      other families. This may indicate that specific mutations play a role in
      determining the number of CHRPEs. Nine affected subjects had intra-abdominal
      desmoids, and in these the frequency of each of the types of CHRPE was no higher
      (in fact, slightly lower) than the average for affected subjects without
      desmoids, but this difference was not significant (p > 0.3).

PMID- 8151640
TI  - The spectrum of beta thalassaemia mutations in the UAE national population.
AB  - The beta thalassaemia alleles in 50 beta thalassaemia heterozygotes originating
      from many parts of the United Arab Emirates (UAE) have been characterised using
      the allele specific priming technique of the polymerase chain reaction (PCR). The
      IVSI-5 (G-->C) mutation was found to be present in 66%, while six other alleles
      occurred at the much lower frequencies of 2% to 8%. These were codon 8/9 (+G),
      IVSI-1, 3' end (-25 bp), codon 5 (-CT), IVSII-1 (G-->A), codon 30 (G-->C), and
      codon 15 (G-->A). The mutation types and percentages are compared with other
      Mediterranean Arab countries and neighbouring areas. It is proposed that IVSI-5
      and other Asian Indian mutations were introduced into the UAE by population
      migration from the region previously known as Baluchistan. These findings should
      be useful for genetic counselling and the development of a first trimester
      prenatal diagnosis programme based on direct detection of mutations in the UAE.

PMID- 8151641
TI  - Liver histology in the arthrogryposis multiplex congenita, renal dysfunction, and
      cholestasis (ARC) syndrome: report of three new cases and review.
AB  - We report three cases from two unrelated families of infants with arthrogryposis
      multiplex congenita, cholestatic jaundice, and renal Fanconi's syndrome. In both
      families the parents were consanguineous. All three children died by 7 months of
      age. This association was first reported in 1973 by Lutz-Richner and Landolt and
      again in another family by Nezelof et al in 1979. However, because of differing
      liver histology the two sibships were considered to have two separate conditions.
      Based on the histological findings in one of our cases we propose that all cases
      described so far represent variation within a single syndrome.

PMID- 8151642
TI  - Two brothers with characteristic facial appearance, severe psychomotor
      retardation, hypospadias, contractures, and other symptoms: a new recessive
      syndrome?
AB  - We report on two severely mentally retarded male children of consanguineous
      parents who seem to be affected by an identical syndrome. The main physical
      anomalies are typical facial stigmata with a broad nasal bridge, a bulbous nose,
      upward slanting palpebral fissures, microretrognathia, low hair line, and large
      ears with an incompletely developed upper helix. In addition, both brothers had
      hypospadias type II, limb contractures, and delayed bone age. One child had a
      bilateral cleft lip with cleft palate and cryptorchidism, and developed scoliosis
      during adolescence. The other had bilateral inguinal hernias and strabismus.
      Chromosome analysis showed a normal karyotype in both. The striking similarity
      between the brothers, the dissimilarity to other known syndromes, and the
      parental consanguinity argue in favour of a new, hitherto undescribed, possibly
      autosomal recessive syndrome.

PMID- 8151643
TI  - Familial leuconychia, knuckle pads, hearing loss, and palmoplantar
      hyperkeratosis: an additional family with Bart-Pumphrey syndrome.
AB  - A family with five members who have variable findings of leuconychia, knuckle
      pads, hearing loss, and palmoplantar hyperkeratosis is described. The findings in
      these subjects are compared with those noted in previously reported patients with
      Bart-Pumphrey syndrome. The range of disorders which include knuckle pads as part
      of the phenotype is reviewed.

PMID- 8151644
TI  - De novo deletion (2) (p11.2p13): clinical, cytogenetic, and immunological data.
AB  - We report a case of a boy with a de novo interstitial deletion of chromosome (2)
      (p11.2p13). Clinical features included dysmorphism of the face, genital region,
      and limbs, psychomotor retardation, and vitiligo. A reduced ratio of
      immunoglobulin (Ig) light chain expression (kappa/lambda ratio: 0.7) was found,
      compatible with deletion of one Ig kappa allele on chromosome 2p12. The patient
      had no clinical or laboratory signs of immunodeficiency.

PMID- 8151645
TI  - Balanced reciprocal whole arm translocation t(3;9): analysis by fluorescence in
      situ hybridisation.
AB  - A patient with Turner phenotype was found to carry two de novo chromosome
      aberrations: a 45,X line and a whole arm reciprocal translocation t(3;9).
      Fluorescence in situ hybridisation on metaphase cells using alpha satellite DNA
      for chromosome 3 and beta satellite and 'classical' satellite DNA for chromosome
      9 showed that the centromeric region of chromosome 3 was retained in the 3q9q
      translocation derivative, as was the secondary constriction heterochromatin of
      chromosome 9. No signals were observed in the 3p9p derivative with the three
      probes. This suggests that the breakpoints were on 3p11 and 9q11. The karyotype
      was 45,X,t(3;9)(3qter-->3p11::9q11-->9qter; 9qter-->9q11::3p11-->3pter).

PMID- 8151646
TI  - Identification by molecular diagnosis of mosaic Turner's syndrome in an obligate
      carrier female for fragile X syndrome.
AB  - A case of mosaic Turner's syndrome with a 45,X/46,XX/47,XXX karyotype, who was
      also a fragile X obligate carrier as the mother of an affected boy, was
      identified by molecular diagnosis. Complete haplotyping and direct DNA analysis
      showed that the X chromosome in all metaphases was the normal X. At the age of
      57, she is mentally normal. Her external appearance was typical of Turner's
      syndrome. This report shows that molecular studies in conjunction with
      cytogenetic analysis can help in the clinical diagnosis of a rare case and can
      show the uniqueness of a case such as the one here described.

PMID- 8151647
TI  - Exclusion of two candidate loci for autosomal recessive nemaline myopathy.
AB  - The putative gene for autosomal recessive nemaline myopathy has not been mapped,
      cloned, or otherwise characterised. We used linkage analysis with polymorphic CA
      repeats to test for the involvement of two candidate loci, APOA2 and ACTN2. Based
      on the segregation in five families both candidate loci could be excluded.

PMID- 8151648
TI  - Analysis of human growth hormone gene 5' sequences in isolated growth hormone
      deficiency patients.
AB  - Human growth hormone (hGH) gene deletion (6.7 to 7.6 kb) is one of the causes of
      isolated growth hormone deficiency (IGHD), named IGHD IA. IGHD IA, however, only
      accounts for about 10% of the total IGHD patients. Most IGHD is caused by unknown
      mechanisms. Here, hGH gene 5' sequences in three IGHD patients without hGH gene
      deletion were analysed to see if there was any mutation hindering the expression
      of the hGH gene.

PMID- 8151649
TI  - Paternal and maternal transmission of pseudohypoparathyroidism type Ia in a
      family with Albright hereditary osteodystrophy: no evidence of genomic
      imprinting.

PMID- 8151650
TI  - Low segregation ratios in autosomal recessive disorders.

PMID- 8151651
TI  - Del(18p) syndrome with a single central maxillary incisor.

PMID- 8151652
TI  - Prevention of Mediterranean anaemia in Latium, Italy, today.

PMID- 8151653
TI  - Samuel Haughton (1821-1897).

PMID- 8151654
TI  - Historical aspects of biomedical engineering: a perspective from recent work in
      the sociology of technology.

PMID- 8151655
TI  - Objects as evidence: the role of museum collections.

PMID- 8151656
TI  - A brief personal account of the Aberdeen story--with particular reference to
      SPECT and MRI.

PMID- 8151657
TI  - Application of art, science and gumption in the care of the disabled.

PMID- 8151658
TI  - Bioengineering in Edinburgh.

PMID- 8151659
TI  - It seemed a good idea at the time.

PMID- 8151660
TI  - Bioengineering at the University of Strathclyde.
AB  - Bioengineering is, of course, no longer regarded as 'new'. Many groups exist in
      many centres in the UK and worldwide. The writer considers himself particularly
      fortunate in having been involved since 1960 in bioengineering research, teaching
      and development following a very satisfying period as a lecturer in mechanics for
      engineering students. On hindsight, the most important feature has been the
      pleasure of association with a succession of talented, intelligent and strongly
      motivated academic colleagues and students devoted to research and development in
      the field of bioengineering.

PMID- 8151661
TI  - Artificial organs and biomaterials.

PMID- 8151662
TI  - Artificial surface--blood interactions.

PMID- 8151663
TI  - Development of prosthetic/orthotic education and training.

PMID- 8151664
TI  - The international development of prosthetics and orthotics.

PMID- 8151665
TI  - Strathclyde-Rostock cooperation.

PMID- 8151666
TI  - Biomedical engineering in Hong Kong--the Scottish connection.

PMID- 8151667
TI  - Smart instrumentation--the example of skin microcirculation.

PMID- 8151668
TI  - Initiatives in the biomedical industry.
AB  - Achievements in the healthcare industry are related to the needs of the patients
      and the surgeons. Often a new technique in surgery forces industry to produce
      products to fulfil the needs of the new techniques. Laparoscopic surgery is a
      good example of this. The reverse is also true: that new discoveries in industry
      allow new procedures to be created around the new industrial achievement. Joseph
      Lister once said 'success is attention towards detail', a truism just as opposite
      today as it was 100 years ago.

PMID- 8151669
TI  - Mass customization of prosthetic and orthotic devices.

PMID- 8151670
TI  - Viral hazards of transfusion: new developments.

PMID- 8151672
TI  - The effect of iron on the invasiveness of Escherichia coli carrying the inv gene
      of Yersinia pseudotuberculosis.
AB  - The effect of growth in iron-excess or iron-limitation conditions on the
      invasiveness for HeLa cells of Escherichia coli HB101 carrying plasmid pRI203
      which bears the invasion gene of Yersinia pseudotuberculosis was examined. Iron
      limitation reduced adhesion and the number of organisms internalised by HeLa
      cells by about 100-fold. The reduced adhesion of iron-starved bacteria correlated
      with reduced hydrophobicity and the reduced invasiveness appeared to depend on
      the plasmid copy number, which was 3.5-fold less than in bacteria grown in iron
      excess.

PMID- 8151671
TI  - Genetic relationships and virulence factors among classical enteropathogenic
      Escherichia coli serogroup O126 strains.
AB  - Thirty-nine Escherichia coli strains of the enteropathogenic (EPEC) serogroup
      O126 isolated from sporadic and outbreak cases of infantile diarrhoea between
      1982 and 1988 were studied. These strains consisted of four serotypes showing
      close genetic relationships between their virulence markers, outer-membrane
      protein and lipopolysaccharide profiles, and electrophoretic types by multilocus
      enzyme electrophoresis. None of these strains exhibited localised adherence to
      HEp-2 cells or the attaching-effacing properties of classical type I EPEC. Of the
      39 strains, 31 were of serotype O126:H12 and enterotoxigenic; one strain was
      serotype O126:H10 and enteroaggregative. The remaining six strains of serotype
      O126:H21 and one strain of serotype O126:H8 harboured no known virulence factors
      for diarrhoeagenic E. coli.

PMID- 8151673
TI  - Diagnosis of infections with Shiga-like toxin-producing Escherichia coli by use
      of enzyme-linked immunosorbent assays for Shiga-like toxins on cultured stool
      samples.
AB  - Shiga-like toxin-producing (SLT) Escherichia coli, particularly those belonging
      to serogroup O157, are responsible for haemorrhagic colitis, haemolytic uraemic
      syndrome and some cases of gastro-enteritis. The rapid and reliable diagnosis of
      all these infections is necessary for correct patient management and for
      epidemiological reasons, but is rarely possible with present methods. We compared
      the efficacy of two methods, (i) the culture of faeces in broth that contained
      mitomycin C followed by enzyme-linked immunosorbent assay (ELISA) for SLTs, and
      (ii) the culture of faeces on sorbitol MacConkey agar (SMA), in the detection of
      infections caused by SLT-producing E. coli. SLT-producing E. coli O157 strains
      were isolated on SMA from 42 of 475 faecal samples, but SLTs were detected by
      ELISA in culture supernates or lysates of 54 of 475 samples. SLT-producing E.
      coli strains were isolated subsequently from 11 of 12 ELISA-positive, SMA culture
      negative samples by a colony blot technique. In four cases, SLT-producing E. coli
      of serogroups other than O157 were isolated and in seven cases E. coli O157 was
      isolated in small numbers. The ELISA is a rapid and sensitive technique for the
      diagnosis of SLT-producing E. coli infection, especially where low numbers of the
      organism are present in faeces and when the infection is caused by a serogroup
      other than O157.

PMID- 8151674
TI  - Influence of animal passage on haemolysin and enterotoxin production in Vibrio
      cholerae O1 biotype El Tor strains.
AB  - Of 43 strains of Vibrio cholerae O1 biotype El Tor isolated over a span of almost
      three decades (1964-1990) from stools of children and adults with diarrhoea (25
      isolates) and from sewage (three) and water from the river Ganges (15) examined
      for production of haemolysin and its correlation with enterotoxin production, 17
      isolates showed haemolysis. The majority of isolates (26), including 68% of
      diarrhoeal and 50% of environmental origin, were non-haemolytic. The titre of
      haemolysin produced was 4-16 HU/ml, irrespective of the source of isolation.
      Haemolytic strains caused significantly more fluid accumulation than the non
      haemolytic strains in the rabbit ileal loop (RIL) test. Twenty nine (67.4) V.
      cholerae biotype El Tor isolates--all the haemolytic and most (61.5%) of the non
      haemolytic isolates tested--caused fluid accumulation. The remaining non
      haemolytic strains that caused little or no accumulation of fluid did so after
      one to four consecutive passage(s) through RIL without change in haemolytic
      character; these strains required more consecutive passage through rabbit gut to
      show haemolysis. All these strains reverted to their original non-haemolytic
      character on repeated subculture or on storage in the laboratory but continued to
      show enterotoxic activity. The present study indicated that El Tor haemolysin is
      not responsible for fluid accumulation in rabbit gut.

PMID- 8151676
TI  - Small-fragment restriction endonuclease analysis in epidemiological mapping of
      group A streptococci.
AB  - The usefulness of small-fragment restriction endonuclease digest analysis (SF
      REA) of group A streptococcal DNA with EcoRI, as a supplement to the more
      conventional T serotyping, was assessed for epidemiological characterisation. One
      hundred and thirty-five clinical isolates from 1988-1990 were examined. SF-REA
      provided characteristic fingerprints of all isolates, whereas eight isolates were
      non-typable by T serotyping. Generally, there was a striking correlation between
      the results obtained with the two techniques. Furthermore, SF-REA reliably
      classified the eight T-non-typable isolates and occasionally revealed subgroups
      within the T serotypes. In addition, SF-REA was useful for the clarification of
      discrepancies between serotyping results from two different reference
      laboratories. No obvious correlation was observed between the DNA fingerprints
      and the clinical manifestations of infection or the geographical origin of the
      group A streptococcal isolates. SF-REA is a valuable supplement to T typing in
      epidemiological studies and frequently appears to be a more efficient tool for
      strain differentiation.

PMID- 8151675
TI  - Effect of inoculum size on the in-vitro susceptibility to beta-lactam antibiotics
      of Moraxella catarrhalis isolates of different beta-lactamase types.
AB  - The effect of inoculum size on the results of agar dilution MIC tests was
      assessed for 20 Moraxella catarrhalis isolates with BRO-1 enzyme, 20 with BRO-2
      enzyme and 15 isolates that did not produce beta-lactamase. The compounds tested
      were ampicillin, coamoxiclav, cefaclor, cefixime and cefetamet, and the inocula
      were 10(4), 10(5), 10(6) and 10(7) cfu/spot. The MICs of ampicillin for BRO-1 and
      BRO-2 producers were consistently higher than those for non-producers at inocula
      of 10(7) cfu/spot but overlapped with those for non-producers at lower inocula. A
      small beta-lactamase-related inoculum effect was seen with coamoxiclav; small
      inoculum effects also occurred with cefaclor and cefixime but were not related to
      enzyme presence or type. MICs of cefetamet were the least affected by the
      inoculum size. For all the compounds, the degree of correlation between MICs and
      the inhibition zones observed in disk diffusion tests was independent of the
      inoculum used in the MIC tests. These data suggest that high inocula should be
      used to determine MICs of ampicillin for M. catarrhalis but that this precaution
      is unnecessary with the cephalosporins tested or with coamoxiclav.

PMID- 8151678
TI  - A particle counting immunoassay for the direct detection of Clostridium difficile
      serogroup specific antigen in faecal specimens.
AB  - The potential of a particle counting immunoassay (PACIA) for the direct detection
      of Clostridium difficile serogroup G specific antigen in faecal specimens was
      evaluated. F(ab')2 fragments from a rabbit anti-serogroup G antiserum were
      covalently coupled to carboxylated latex beads. This reagent was mixed with acid
      extracts of faecal specimens and the reaction was assayed with an optical counter
      which discriminated unagglutinated from agglutinated latex particles. Culture for
      C. difficile, faecal cytotoxin detection, PACIA and serogrouping of C. difficile
      isolates were performed on 249 stools. Of the 71 culture-negative specimens, none
      gave a positive result in the cytotoxin assay or in PACIA. Faecal cytotoxin was
      detected in 100 of the 178 culture-positive specimens. PACIA was positive for 63
      of the 71 faecal specimens that yielded serogroup G C. difficile on culture.
      PACIA gave negative results for all other culture-positive stools tested with one
      exception, from which a serogroup A7 C. difficile strain was isolated. PACIA
      detection of serogroup G antigen in faecal specimens showed a sensitivity of
      88.7%, a specificity of 99.7%, a predictive value of a positive culture with a
      serogroup G strain of 98.4%, and a predictive value for specimens that were
      culture-negative for a serogroup G strain of 95.6%. The results indicate that
      PACIA with specific antiserum is a rapid and reliable method for detecting
      serogroup specific antigens of C. difficile in faecal specimens. Clinical
      applications of the method are discussed.

PMID- 8151677
TI  - IgG subclass response and protection against challenge following immunisation of
      mice with various influenza A vaccines.
AB  - The serum total IgG and IgG subclass and nasal wash IgA and IgG antibody
      responses of mice to influenza virus A/Hong Kong/68 (H3N2) subunit preparations
      administered parenterally as a single dose, incorporated either in immune
      stimulatory compounds (ISCOMs) or liposomes with Freund's Complete Adjuvant, or
      as an aqueous material, as well as to live, infectious virus were measured by
      ELISA at 10 days and 3, 5, 7 and 22 weeks after immunisation. The protection of
      the upper and lower respiratory tracts provided by these preparations against
      homologous and heterologous challenge infection was assessed. Of the four
      variously-presented subunit preparations, influenza subunit ISCOMs induced
      relatively high and persisting levels of each of the different IgG subclasses,
      particularly IgG2a, throughout the study, and most nearly approached those
      observed after intranasal infection of mice with infectious virus. Furthermore,
      nasal wash IgA and IgG antibody levels, particularly at 5 or 7 weeks after
      immunisation, were also significantly greater in mice given the subunit ISCOM
      preparation than those induced by other subunit preparations with adjuvant or
      subunits given alone, and provided protection of both the upper and lower
      respiratory tracts against challenge as similar to that elicited by infectious
      virus.

PMID- 8151679
TI  - Differentiation of Pseudomonas aeruginosa strains by ribotyping: high
      discriminatory power by using a single restriction endonuclease.
AB  - The genotypic diversity of 40 presumably epidemiologically unrelated strains of
      Pseudomonas aeruginosa belonging to nine different O-serotypes was analysed
      according to ribosomal DNA fingerprints. Ribotyping was performed with a
      digoxigenin-labelled DNA probe and four restriction endonucleases. Characteristic
      banding patterns of three to 12 bands were obtained with the different
      endonucleases. Among the 40 strains, eight, nine, 10 and 29 different ribotypes
      were differentiated with EcoRI, the combination EcoRI+HindIII, BamHI and PvuII,
      respectively. Poor correlations were noted between the results of serotyping and
      those of ribotyping. With the latter method, indices of discrimination were
      calculated for each enzyme from the data of the 40 unrelated strains: the values
      ranged from 0.678 for EcoRI to 0.979 for PvuII. Epidemiologically related samples
      were also tested; this enabled assessment of whether the method was able to
      cluster strains from a common origin with each of the enzymes tested. Ribotyping
      with PvuII endonuclease is proposed for screening large numbers of P. aeruginosa
      strains in epidemiological studies. Additional enzymes could be used to further
      increase the discrimination between isolates found to be indistinguishable with
      PvuII enzyme.

PMID- 8151680
TI  - Characterisation of the external surfaces of Pseudomonas aeruginosa isolated from
      human blood and respiratory tract.
AB  - The surface structures of the cell envelopes of 16 clinical isolates of
      Pseudomonas aeruginosa were examined by electronmicroscopy with the new fixation
      technique of freeze-substitution. Two types of structures were observed among the
      organisms. In one group of strains, mostly isolated from blood, a dense fibrous
      layer c. 30 nm thick was found around the outer-membrane surface, whereas no such
      structure was observed in the other group of isolates, most of which were from
      sputum. Lipopolysaccharides extracted from the isolates with a dense fibrous
      layer were found by SDS-PAGE to have long O-polysaccharide chains, whereas
      strains without such a layer mostly had lipopolysaccharides that lacked high mol.
      wt. O-polysaccharide chains.

PMID- 8151681
TI  - The role of IgA determination by ELISA in the early serodiagnosis of Mycoplasma
      pneumoniae infection, in relation to IgG and mu-capture IgM methods.
AB  - Enzyme-linked immunosorbent assay (ELISA) for IgA, IgG and IgM was evaluated with
      sera from 50 adult patients with pneumonia, selected on the basis of a positive
      complement fixation (CF) test for diagnosis of Mycoplasma pneumoniae infection
      and with sera from 105 healthy blood donors. The ELISA antigen for IgG and IgA
      was a sonicated suspension of M. pneumoniae solubilised by deoxycholate. For the
      IgM assay, the same antigen was directly conjugated to alkaline phosphatase and
      used in a mu-capture format. ELISA gave positive results with high or rising
      titres for one or several antibody classes in 47 (94%) patients. In two of the
      three ELISA-negative cases, the diagnosis of M. pneumoniae infection indicated by
      the CF test seemed unlikely on clinical grounds. Specific IgA antibodies was
      developed more regularly and more rapidly than IgM. IgA titres also started to
      decrease earlier than IgM or the late-peaking IgG response. Thus, the
      determination of IgA antibodies was found to be valuable for the early diagnosis
      of M. pneumoniae infection. The study also demonstrated that the determination of
      all three antibody classes is necessary to obtain an optimal level of
      serodiagnosis.

PMID- 8151682
TI  - Diagnosis of Lyme borreliosis: non-specific serological reactions with Borrelia
      burgdorferi sonicate antigen caused by IgG2 antibodies.
AB  - ELISA methods that measure IgG class antibodies to sonicated Borrelia burgdorferi
      may give false positive results. These errors could be traced to non-specific
      reactivity in subclass IgG2 in several instances. Sera were sampled randomly from
      two adult populations, which differed in having a high and low incidence of Lyme
      disease. If the binding of IgG2 subclass antibodies was left unrecorded in the
      test by the use of monoclonal reagent antibodies selective for IgG1 and IgG3, the
      frequency of positivity in the ELISA test decreased in samples from the low risk
      group. Twenty-one samples were found to be positive in an immunoblot confirmatory
      test. Correct prediction of positivity was obtained for 15 sera by ELISA
      restricted to IgG1 plus IgG3, for only four sera by ELISA restricted to IgG2 and
      for only six sera by IgG subclass non-restricted ELISA. A non-restricted ELISA
      with purified flagella of B. burgdorferi as the antigen predicted correctly 14 of
      the immunoblot-positive sera. The results of this ELISA correlated well with
      those of the IgG1 plus IgG3 subclass restricted ELISA in the high risk population
      (r = 0.95, prevalence of seropositivity 12%), but was significantly worse for the
      low risk group (r = 0.47, prevalence 2.9%). IgG subclass restriction also
      decreased cross-reactions of syphilitic sera in the ELISA with sonicated antigen.

PMID- 8151683
TI  - The Bloodborne Pathogens Standard and staff training.

PMID- 8151684
TI  - New TV spot highlights '93 media plan.

PMID- 8151685
TI  - New recommendations announced for HIV-infected and HBV-infected health care
      workers.

PMID- 8151686
TI  - The secrets of leadership.

PMID- 8151687
TI  - Requirements for extracted teeth disposal.

PMID- 8151688
TI  - On your mark ... get set...

PMID- 8151689
TI  - AIDS and dental office safety--what Michigan's residents really think.

PMID- 8151690
TI  - Patient and dental student responses to a survey about AIDS in the dental
      setting.
AB  - The purpose of the study was to gain information about patients' and dental
      students' attitudes concerning AIDS and dentistry. Opinions of patients and
      students at a Midwestern dental school were surveyed. The dental students'
      responses were not as consistent as the patient responses. Both groups felt there
      was a risk to patients and dentists of HIV infection. Both groups had confidence
      in the CDC infection control guidelines. The patient responses to the testing
      questions were significantly more positive than the student responses. The
      patients responded positively to the concept that healthcare professionals had
      the right to ask patients to be tested and to being required to be tested if a
      healthcare provider is accidentally stuck by a needle used on a patient. The
      dental students were more cautious with both issues. Patients would use knowledge
      about a healthcare provider's HIV status and the office treatment of AIDS
      patients to determine if they should continue treatment at that dental office.

PMID- 8151691
TI  - Two sides of the Sargenti question.

PMID- 8151692
TI  - Dental lasers--is the future now?

PMID- 8151693
TI  - 10 Common safety and health violations ... here's how to avoid them.

PMID- 8151695
TI  - Mississippi State Board of Medical Licensure annual report. July 1, 1992 through
      June 30, 1993.

PMID- 8151694
TI  - Total abdominal colectomy for control of massive lower gastrointestinal bleeding.
AB  - From 1957-1990 four patients underwent total abdominal colectomy with primary
      ileoproctostomy for control of massive lower gastrointestinal hemorrhage at Field
      Memorial Community Hospital in the rural community of Centreville, Mississippi.
      Surgery was performed emergently in two cases, and urgent/electively in the two
      remaining cases. Bleeding was controlled in each case. Upper Gastrointestinal and
      rectal bleeding were excluded, but further attempts to localize bleeding were not
      performed due to the difficulty of obtaining these studies at our hospital and
      the questionable likelihood of localizing the bleeding site. Many authors
      recommend an aggressive diagnostic workup including radio-labeled RBC
      scintigraphy and mesenteric angiography to localize colonic bleeding. Their aim
      is to perform a directed colonic resection for control of bleeding. However, most
      authors support total abdominal colectomy in cases where 1) hemodynamic
      instability does not allow extensive preoperative evaluation 2) there is a
      recurrent bleeding 3) more than one site is visualized as bleeding 4) there is
      widespread diverticulosis in a good-risk patient or 5) diagnostic procedures are
      unavailable. The low morbidity and good bowel function achieved following total
      abdominal colectomy, combined with the unavailability of diagnostic radiographic
      studies leads us to recommend total abdominal colectomy for control of massive
      lower gastrointestinal bleeding. The mortality of the procedure can be minimized
      by operating in a timely manner, prior to 10 units transfusion or 4 units within
      24 hours, or operating in cases of recurrent bleeding.

PMID- 8151696
TI  - Government medicine--Canadian style.

PMID- 8151697
TI  - Prediction of the folding pathways and structure of the GCN4 leucine zipper.
AB  - A hierarchical approach is described for the prediction of the three-dimensional
      structure and folding pathway of the GCN4 leucine zipper. Dimer assembly is
      simulated by Monte Carlo dynamics. The resulting lowest energy structures undergo
      cooperative rearrangement of their hydrophobic core leading to side-chain
      fixation. The coarse-grained structures are further refined using a molecular
      dynamics annealing protocol. This produces full atom models with a backbone root
      mean-square deviation from the crystal structure of 0.81 A. Thus, we demonstrate
      the predictive ability of our approach to yield high resolution structures of
      small coiled coils from their sequence.

PMID- 8151698
TI  - Specialized ribosomes allow for the study of mutations in functionally important
      regions in 16 S rRNA, without affecting cell growth. The identification of
      functional regions in the central domain of 16S rRNA.
AB  - In order to identify the sequences in the central domain of 16 S rRNA of
      Escherichia coli that are important for ribosome function, we have generated
      random mutations using a PCR-based mutagenesis technique. We show that the
      effects of such mutations on ribosomal activity can be analyzed in vivo utilizing
      the specialized ribosome system. With this system the effect of rRNA mutations on
      ribosomal activity can be studied by measuring the translation of a modified CAT
      mRNA by specialized ribosomes. Specialized ribosomes do not translate the
      endogenous mRNAs and, therefore, are expected to constitute a non-essential pool
      of ribosomes within the cell. In total, we have isolated 28 different clones
      harboring specialized ribosomes with single or multiple point mutations. We
      demonstrate that for none of these clones was cell growth retarded, even though
      some of the mutations severely impaired the activity of the specialized
      ribosomes, to as low as 3% of the wild-type level. For all mutants, their
      individual activities ranged between 3% and 100% of that of the wild-type
      activity. Comparison of several mutants indicates that mutations within the
      hairpin loops 787-795 and 898-901 strongly reduce the ribosomal activity. We also
      present evidence that the single-stranded region centered around residue A815 may
      be involved in maintaining translational accuracy.

PMID- 8151699
TI  - Linking an easily detectable phenotype to the folding of a common structural
      motif. Selection of rare turn mutations that prevent the folding of Rop.
AB  - Rop is the simplest and most regular member of a family of proteins characterized
      by a bundle of four antiparallel helices. Rop is dimeric, each monomer being
      formed by two helices connected by a sharp bend. In this work we have extensively
      mutagenized three residues that form the connection between the two alpha-helices
      to ask whether the bend region contains any important folding information. The
      characterization of a collection of random mutants indicated that this structure
      is rather insensitive to amino acid substitutions and that most amino acids are
      tolerated in these positions by the Rop native structure. In order to identify
      the rare amino acid sequences that would prevent Rop from folding and/or
      dimerizing, we exploited the observation that Rop can functionally substitute the
      dimerization domain of the lambda repressor. In fact plasmids expressing a hybrid
      protein formed by the amino-terminal domain of the lambda repressor covalently
      linked to Rop, confer immunity to lambda infection on their hosts. We have shown
      that this property depends on the ability of the Rop moiety to fold and dimerize.
      The analysis of 380 Rop mutants containing random amino acid sequences at
      positions 30, 31 and 32 allowed us to identify three mutant Rop proteins that are
      defective in dimerization, probably as a consequence of their inability to fold.
      In these mutants the tripeptides VED, VPD and YPD substitute the wild-type DAD at
      positions 30, 31 and 32. Other combinations of amino acids are found resulting in
      levels of immunity that are lower than the wild-type but still sufficient to
      prevent single plaque formation. This result suggests that a smaller proportion
      of the corresponding Rop protein reaches a thermodynamic and proteolytically
      stable dimeric state.

PMID- 8151700
TI  - Multiple DNA conformational changes induced by an initiator protein precede the
      nicking reaction in a rolling circle replication origin.
AB  - The core origin for plus strand DNA replication of filamentous bacteriophage f1
      binds the initiator protein (gpII), which subsequently introduces a specific nick
      in the plus strand. The core origin consists of a nicking region and a binding
      region. The binding of gpII occurs in two steps, forming a binding intermediate
      (complex I) and a functional complex for nicking (complex II). Results of gel
      retardation experiments using circularly permuted DNA fragments and direct
      visualization by electron microscopy show that gpII induces successive bends
      within the binding region upon formation of the complexes. We show that gpII
      binding induces duplex melting in the nicking region using KMnO4 modification of
      unpaired thymidine residues as a probe for melting. Origin binding occurred in
      the absence of superhelicity of DNA and Mg2+, whereas duplex melting required
      superhelical DNA, but not Mg2+. Deletion analyses indicated that hypothetical
      formation of a cruciform around the nicking site is not necessary for either
      melting or nicking. A mutation in gpII resulted in stimulation of duplex melting
      and nicking without showing obvious effects on bending. This suggests that the
      mechanism of melting involves local interaction between gpII and the nicking
      region. Furthermore, using synthetic oligonucleotide substrates, we show that the
      nicking reaction takes place efficiently when the nicking region is single
      stranded and the binding region is double-stranded. These results indicate that
      the nicking reaction is preceded by an ordered series of protein-induced DNA
      conformational changes: successive bending of the origin upon gpII binding,
      followed by duplex melting that requires negative superhelicity.

PMID- 8151701
TI  - Nucleosome positioning on chicken and human globin gene promoters in vitro. Novel
      mapping techniques.
AB  - We have developed two new techniques to assess the positions adopted by core
      histone octamers when reconstituted onto DNA. These, together with a previously
      described technique, were applied to mapping binding sites on plasmid DNAs
      containing either the human zeta-globin or chicken beta-globin gene promoters.
      Each of the approaches enabled the sites occupied by histone octamers to be
      measured at high resolution and, in qualitative terms, revealed the same pattern
      of multiple, overlapping sites. Monomer extension, one of the novel techniques,
      can be used to reveal binding sites over extensive stretches of a single
      reconstitute (approximately 1000 bp). We found the distribution of histone
      octamer binding sites to be largely independent of the conditions employed for
      reconstitution, the topology of the DNA substrate and prolonged incubation under
      various post-reconstitution conditions. These properties, and features of the
      binding site maps that we derived, suggest that histone octamer positioning on
      these DNAs is predominantly a characteristic of the DNA sequence itself and, by
      implication, that nucleosome-nucleosome interactions and the formation of
      nucleosome arrays are of minor influence. Some of the techniques provide
      quantitative information concerning the relative binding strengths of the core
      histone octamer for different positioning sequences. In this context, it is
      notable that the majority of potential binding sites compete very poorly for the
      histone octamer, demonstrating that under the conditions pertinent to our
      analysis, the range of binding strengths exhibited by the octamer for particular
      DNA sequences is extensive, and greater than that observed when competitive
      binding has been studied by methods that do not reflect precise positioning.

PMID- 8151702
TI  - Selection of beta-lactamase on filamentous bacteriophage by catalytic activity.
AB  - Recently the display of repertoires of peptides and proteins on the surface of
      filamentous phage, and selection of the phage by binding to a ligand, has allowed
      the isolation of peptides and proteins with rare binding activities. Furthermore,
      phages displaying enzymes (phage enzymes) have been selected by affinity of
      binding to inhibitors. Here we show, using a suicide inhibitor, that phage
      enzymes can also be selected by their catalytic activity. Two phage enzymes were
      constructed by fusion to the minor coat protein of the phage (g3p), displaying
      either an active beta-lactamase or a catalytically inactive mutant in which the
      essential serine of the active site was mutated to alanine. The phages were then
      incubated with a beta-lactamase suicide inhibitor connected by a spacer to a
      biotin moiety. The active (but not the inactive) phages were labelled, and the
      active phages selected from mixtures with inactive phages by binding and elution
      from streptavidin-coated beads. The selection ratio for active versus inactive
      phages (about ten on elution of the phages by reduction of an S-S bond in the
      spacer between the warhead and biotin) could be improved to about 50 on elution
      by proteolytic cleavage of beta-lactamase from g3p at an intervening factor X
      site. Selection of phage-enzymes by catalysis may provide a means of creating new
      enzymes and refining their catalytic properties.

PMID- 8151703
TI  - Aspects of receptor binding and signalling of interleukin-4 investigated by site
      directed mutagenesis and NMR spectroscopy.
AB  - Cytokines are hormones that carry information from cell to cell. This information
      is read from their surface upon binding to transmembrane receptors and by the
      subsequent initiation of receptor oligomerization. An influence on this process
      through mutagenesis on the hormone surface is highly desirable for medical
      reasons. However, an understanding of hormone-receptor interactions requires
      insight into the structural changes introduced by the mutations. In this line
      structural studies on human IL-4 and the medically important IL-4 antagonists
      Y124D and Y124G are presented. The site around Y124 is an important epitope
      responsible for the ability of IL-4 to cause a signal in the target cells. It is
      shown that the local main-chain structure around residue 124 in the variants
      remains unchanged. A strategy is presented here which allows the study of these
      types of proteins and their variants by NMR which does not require carbon
      labelled samples.

PMID- 8151704
TI  - Crystal structures of aconitase with trans-aconitate and nitrocitrate bound.
AB  - Crystal structures of mitochondrial aconitase with the inhibitors trans-aconitate
      and nitrocitrate bound to the [4Fe-4S] cluster have been solved and refined at
      2.05 A resolution with R-factors of 0.168 and 0.172, respectively.
      Crystallization of aconitase with the substrates citrate and cis-aconitate has
      not been possible because the enzyme turns over and selects enzyme with
      isocitrate bound into the crystal lattice. Therefore we have analyzed crystal
      structures of the enzyme complexed with inhibitor analogs of these two
      substrates. The structure with nitrocitrate bound provides a model for citrate
      binding. The structure with trans-aconitate bound provides a model for cis
      aconitate binding in two ways: Fe4 of the [4Fe-4S] cluster is five-coordinate and
      the carbon at the C beta position is trigonal. These results allow the model for
      the reaction mechanism to be extended to all three natural substrates of
      aconitase. The results support a model in which citrate and isocitrate form
      similar chelate structures related by 180 degrees rotation about the C alpha-C
      beta bond while the intermediate cis-aconitate binds in either of two ways
      (citrate mode or isocitrate mode). In both inhibitor complexes a H2O molecule is
      also bound to Fe4. In the structure with nitrocitrate bound, partial occupancy of
      sulfate in the active site is observed accompanied by hydroxyl binding to Fe4.
      Comparison of the structures with isocitrate, trans-aconitate, nitrocitrate and
      sulfate bound reveals preferred orientations for the three types of oxygens
      ligated to Fe4 (carboxyl, hydroxyl and H2O) supporting the proposed roles for
      His101, Asp165 and His167 in the catalytic mechanism.

PMID- 8151705
TI  - Mutagenesis of the paracrystalline surface protein array of Aeromonas salmonicida
      by endogenous insertion elements.
AB  - The tetragonal paracrystalline surface protein array (A-layer) of the fish
      pathogenic bacterium Aeromonas salmonicida is a virulence factor and bacteria
      which are unable to produce A-layer are attenuated in their ability to kill fish.
      Ten independent mutants of Aeromonas salmonicida which were unable to produce A
      layer were isolated by growth at 30 degrees C. These mutants displayed either
      reduced synthesis of the A-layer subunit, synthesis of a truncated subunit, or
      complete loss of the ability to produce the subunit protein. Restriction mapping
      and analysis by polymerase chain reaction showed that the mutations had resulted
      from insertion of two different insertion sequence (IS) elements into different
      sites in the A-layer subunit gene (vapA) and its promoter. Sequence comparisons
      indicated that ISAS1 is unique among reported IS elements. It is 1223 bp long
      with imperfect terminal inverted repeats of 22 bp and insertion resulted in a
      duplicated 8 bp target sequence in vapA. ISAS1 expressed a 42,000 molecular
      weight (M(r)) protein in mini-cells. ISAS2 was 1084 bp long, expressed proteins
      of M(r) 38,000 and 39,000 in vitro, had imperfect 29 bp terminal inverted repeats
      and had duplicated a 3 bp target sequence. Sequence comparisons indicated that
      ISAS2 was also unique to A. salmonicida; however, the proteins encoded by ISAS2
      showed strong homology to the putative transposases encoded by the IS30 family of
      IS elements. Southern analyses showed that both ISAS1 and ISAS2 were restricted
      to A. salmonicida strains A449 and A450 where they were present in low copy
      number. The ability of these two IS elements to mutate the ability of A.
      salmonicida to produce its paracrystalline surface array provides a novel method
      for the attenuation of virulence.

PMID- 8151706
TI  - The interhexameric contacts in the four-hexameric hemocyanin from the tarantula
      Eurypelma californicum. A tentative mechanism for cooperative behavior.
AB  - Arthropod hemocyanins (Hcs) are regular assemblies of 1, 2, 4, 6 or 8 hexameric
      protein molecules. They transport oxygen and can bind it in a cooperative manner.
      The hexameric X-ray structures of Panulirus interruptus (spiny lobster) and of
      Limulus polyphemus (horseshoe crab) subunit II Hc were solved recently by the
      groups of Hol (Groningen, The Netherlands) and Magnus (Cleveland, U.S.A.). They
      related cooperativity to a rotational movement of a domain within a subunit and
      of the two trimers mutually inside the hexamer. In our study a model was derived
      for the structure and related to the function of the four-hexameric Hc from the
      tarantula Eurypelma californicum by combining data from electron microscopy and
      image processing, from the X-ray diffraction studies mentioned earlier and from
      amino acid sequence studies. Interhexameric contacts were determined at the level
      of secondary structure elements and in some cases of single amino acids. Loops,
      undefined in the X-ray structures of the hexamers, were often involved in these
      contacts. In one case the contact was formed between four parallel alpha-helices,
      two from each hexamer. Based on these findings a mechanism is proposed for the
      transmission of cooperativity between the hexamers, in which the concept of
      "helical friction" plays a key role.

PMID- 8151707
TI  - Structural and electrophysiological analysis of annexin V mutants. Mutagenesis of
      human annexin V, an in vitro voltage-gated calcium channel, provides information
      about the structural features of the ion pathway, the voltage sensor and the ion
      selectivity filter.
AB  - Annexin V binds to phospholipids in a calcium-dependent manner and exhibits
      calcium channel activity in vitro. We prepared a variety of mutants yielding
      information about the structure-function relationship of the ion channel
      activity. All mutants were characterized by X-ray crystallography, electron
      microscopy and electrophysiological measurements. Their structures are
      insignificantly changed whereas their electrophysiological properties are
      drastically different. Glu95, located in the central hydrophilic pore of the
      molecule, is crucial for the ion selectivity filter as its exchange leads to
      reduced calcium and increased sodium conductance. The removal of Glu17, located
      on the protein surface and far from the ion conduction pathway, leads to the
      appearance of a second conductance level of 9 pS in addition to the conductance
      level of about 30 pS in the wild-type molecule. This was also the case for Glu78,
      which is part of a weak calcium binding site. The exchange of Glu17 and Glu78
      produced a mutant retaining only the smaller conductance level. We conclude that
      these two residues influence the angle between the two halves of the molecule,
      which determines the diameter of the ion conduction pathway, thereby leading to
      the occurrence of a second conductance level.

PMID- 8151708
TI  - The role of interhelical ionic interactions in controlling protein folding and
      stability. De novo designed synthetic two-stranded alpha-helical coiled-coils.
AB  - The role of interchain ionic interactions in controlling protein folding and
      stability has been studied by using de novo designed synthetic two-stranded alpha
      helical coiled-coils. The model coiled-coil (denoted as EK) consists of two
      identical 35-residue polypeptide chains with a heptad repeat KgLaGbAcLdEeKf and a
      Cys residue at position 2 and an Ala residue at position 16 in each chain. The
      Lys residues at positions "g" in one chain and Glu residues at positions "e" in
      the other chain are expected to form interchain ion-pairs in the coiled-coil
      structure. This peptide forms a stable coiled-coil structure in benign medium (50
      mM KCl, 25 mM PO4, pH7) with a [urea]1/2 value of 3.5 M. In contrast, two peptide
      analogs EE (EgLaGbAcLdEeKf) and KK (KgLaGbAcLdKeEf), which differ from EK in that
      EE contains only negatively charged Glu residues and KK contains only positively
      charged Lys residues at both positions e and g, each show a random coil structure
      in benign buffer. However, peptide EE or KK can form a stable coiled-coil
      structure if the interchain ionic repulsions are effectively suppressed either by
      changing pH or by using high salt concentrations. An equimolar mixture of these
      two peptides displays 100% alpha-helical content under the same conditions. These
      results demonstrate that although the interhelical ionic attractions are not
      essential for coiled-coil formation, a large number of these weak interactions
      can play an important role in the assembly of helices. Though interhelical ionic
      repulsions destabilize the homo-stranded coiled-coil, electrostatic attractions
      may stabilize the hetero-stranded coiled-coil. In addition, this study also
      suggests that the folding process for these synthetic model coiled-coils does not
      involve a single-stranded alpha-helix as a significantly populated folding
      intermediate.

PMID- 8151710
TI  - A skewed distribution of amino acids at recognition sites of the hypervariable
      region of immunoglobulins.
AB  - Antibody binding site are formed by six hypervariable regions or complementarity
      determining regions (CDRs). The CDRs, three from the heavy chain and three from
      the light chain, are known as hypervariable segments and provide a surface
      complementary to that of the epitope. In recent work it was found that the amino
      acids in these positions fulfill different functions: Some play a structural role
      and others are involved in the specificity-determining function. It is reported
      here that the frequency of amino acids at hypervariable sites is skewed. By means
      of an informational algorithm, key physicochemical attributes of the dominant
      residues were identified for some of those sites. The results for about 1,500
      antibodies suggest that approximately 35% of sites involved in the recognition
      process require only general properties such as composition, volume, and bulk or
      hydrogen bonding which are satisfied by a small set of amino acids instead of any
      one particular complementary amino acid.

PMID- 8151709
TI  - Molecular evolution of the HSP70 multigene family.
AB  - Eukaryotic genomes encode multiple 70-kDa heat-shock proteins (HSP70s). The
      Saccharomyces cerevisiae HSP70 family is comprised of eight members. Here we
      present the nucleotide sequence of the SSA3 and SSB2 genes, completing the
      nucleotide sequence data for the yeast HSP70 family. We have analyzed these yeast
      sequences as well as 29 HSP70s from 24 additional eukaryotic and prokaryotic
      species. Comparison of the sequences demonstrates the extreme conservation of
      HSP70s; proteins from the most distantly related species share at least 45%
      identity and more than one-sixth of the amino acids are identical in the aligned
      region (567 amino acids) among all proteins analyzed. Phylogenetic trees
      constructed by two independent methods indicate that ancient molecular and
      cellular events have given rise to at least four monophyletic groups of
      eukaryotic HSP70 proteins. Each group of evolutionarily similar HSP70s shares a
      common intracellular localization and is presumed to be comprised of functional
      homologues; these include heat-shock proteins of the cytoplasm, endoplasmic
      reticulum, mitochondria, and chloroplasts. HSP70s localized in mitochondria and
      plastids are most similar to the DnaK HSP70 homologues in purple bacteria and
      cyanobacteria, respectively, which is consistent with the proposed prokaryotic
      origin of these organelles. The analyses indicate that the major eukaryotic HSP70
      groups arose prior to the divergence of the earliest eukaryotes, roughly 2
      billion years ago. In some cases, as exemplified by the SSA genes encoding the
      cytoplasmic HSP70s of S. cerevisiae, more recent duplication events have given
      rise to subfamilies within the major groups. The S. cerevisiae SSB proteins
      comprise a unique subfamily not identified in other species to date. This
      subfamily appears to have resulted from an ancient gene duplication that occurred
      at approximately the same time as the origin of the major eukaryotic HSP70
      groups.

PMID- 8151711
TI  - Amplification of the ancient murine Lx family of long interspersed repeated DNA
      occurred during the murine radiation.
AB  - We identified and characterized the relics of an ancient rodent L1 family,
      referred to as Lx, which was extensively amplified at the time of the murine
      radiation about 12 million years ago, and which we showed was ancestral to the
      modern L1 families in rat and mouse. Here we have extended our analysis of the Lx
      amplification by examining more murine and nonmurine species for Lx sequences
      using both blot hybridization and the polymerase chain reaction for a total of 36
      species. In addition we have determined the relative copy number and sequence
      divergence, or age, of Lx elements in representative murine genera. Our results
      show that while Lx sequences are confined to murine genera, the extent of the
      amplification was different in the different murine lineages, indicating that the
      amplification of Lx did not precede, but was coincident with, the murine
      radiation. The implications of our findings for the evolutionary dynamics of L1
      families and the utility of ancestral amplification events for systematics are
      discussed.

PMID- 8151712
TI  - Tail-to-tail orientation of the Atlantic salmon alpha- and beta-globin genes.
AB  - We report the cloning of a cDNA and two corresponding beta-globin genes of the
      Atlantic salmon (Salmo salar L.) as well as two genes for alpha-globins.
      Nucleotide sequence analysis of the cDNA shows that the predicted beta-globin
      peptide comprises 148 amino acids with a calculated molecular mass of 16,127 Da
      and an overall amino acid similarity of 40-50% to higher vertebrates and 60-90%
      to fish sequences. The study of the genomic organization of alpha- and beta
      globin genes shows that, as is the case in Xenopus, the salmon genes are
      adjacent. Two sets of linked alpha- and beta-globin genes were isolated and
      restriction-enzyme polymorphisms indicate that they belong to two distinct loci,
      possibly as a result of the salmon tetraploidy. In each locus the alpha- and beta
      globin genes are oriented 3' to 3' relative to each other with the RNA coding
      sequences located on opposite DNA strands. This is the first evidence for this
      type of arrangement found for globin genes. Moreover, while the linkage found in
      salmon and Xenopus supports the hypothesis of an initial tandem duplication of a
      globin ancestor gene, our results raise the question of the actual original
      orientation of the duplicated genes.

PMID- 8151713
TI  - Possible implications of CpG avoidance in the flatworm Schistosoma mansoni.
AB  - We report the analysis of the biases of CpG, TpG, and CpA of all the DNA
      sequences data from the Trematode Schistosoma mansoni. Our results show CpG
      avoidance whereas TpG and CpA frequencies are over the expected values. These
      characteristics are similar to the biases displayed by methylated genomes, but in
      platyhelminths 5mC has not been detected by biochemical methods. The possible
      implications of this CpG shortage are discussed.

PMID- 8151714
TI  - Phylogenetic relationships among extant classes of echinoderms, as inferred from
      sequences of 18S rDNA, coincide with relationships deduced from the fossil
      record.
AB  - In spite of the rich fossil record and multiple descriptions of morphological and
      embryological characteristics, the origin and subsequent evolution of echinoderms
      remain highly controversial issues. Using sequence data derived from 18S rDNA, we
      have investigated the phylogenetic relationships among five extant classes of
      echinoderms--namely, crinoids, asteroids, ophiuroids, echinoids, and
      holothurians. Almost complete sequences of 18S rDNA were determined for one
      species in each class, and phylogenetic trees were constructed both by the
      neighbor-joining method and by the maximum-likelihood method, with a hemichordate
      as an outgroup. The trees constructed by these methods support the hypothesis
      that the phylum Echinodermata can be subdivided into two subphyla, Pelmatozoa and
      Eleutherozoa. The class Holothuroidea, which has been the subject of debate with
      respect to whether the members are primitive or advanced echinoderms, did not
      occupy a primitive position but had an affinity for the class Echinoidea. Since
      both trees gave different branching topologies for the order of emergence of
      asteroids and ophiuroids, it seems likely that these two groups emerged within a
      very short period of time. A rough estimate of the timing of the divergence of
      the five classes from the present molecular analysis coincided with that deduced
      from the fossil record.

PMID- 8151715
TI  - Reduction of synonymous substitutions in the core protein gene of hepatitis C
      virus.
AB  - Molecular evolutionary analyses were carried out to elucidate the phylogenetic
      relationships, the evolutionary rate, and the divergence times of hepatitis C
      viruses. Using the nucleotide sequences of the viruses isolated from various
      locations in the world, we constructed phylogenetic trees. The trees showed that
      strains isolated from a single location were not necessarily clustered as a
      group. This suggests that the viruses may be transferred with blood on a
      worldwide scale. We estimated the evolutionary rates at synonymous and
      nonsynonymous sites for all genes in the viral genome. We then found that the
      rate (1.35 x 10(-3) per site per year) at synonymous sites for the C gene was
      much smaller than those for the other genes (e.g., 6.29 x 10(-3) per site per
      year for the E gene). This indicates that a special type of functional constraint
      on synonymous substitutions may exist in the C gene. Because we found an open
      reading frame (ORF) with the C gene region, the possibility exists that
      synonymous substitutions for the C gene are constrained by the overlapping ORF
      whose reading frame is different from that of the C gene. Applying the
      evolutionary rates to the trees, we also suggest that major groups of hepatitis C
      viruses diverged from their common ancestor several hundred years ago.

PMID- 8151716
TI  - P-type ATPases of eukaryotes and bacteria: sequence analyses and construction of
      phylogenetic trees.
AB  - The amino acid sequences of 47 P-type ATPases from several eukaryotic and
      bacterial kingdoms were divided into three structural segments based on
      individual hydropathy profiles. Each homologous segment was (1) multiply aligned
      and functionally evaluated, (2) statistically analyzed to determine the degrees
      of sequence similarity, and (3) used for the construction of parsimonious
      phylogenetic trees. The results show that all of the P-type ATPases analyzed
      comprise a single family with four major clusters correlating with their cation
      specificities and biological sources as follows: cluster 1: Ca(2+)-transporting
      ATPases; cluster 2: Na(+)- and gastric H(+)-ATPases; cluster 3: plasma membrane
      H(+)-translocating ATPases of plants, fungi, and lower eukaryotes; and cluster 4:
      all but one of the bacterial P-type ATPases (specific for K+, Cd2+, Cu2+ and an
      unknown cation). The one bacterial exception to this general pattern was the
      Mg(2+)-ATPase of Salmonella typhimurium, which clustered with the eukaryotic
      sequences. Although exceptions were noted, the similarities of the phylogenetic
      trees derived from the three segments analyzed led to the probability that the N
      terminal segments 1 and the centrally localized segments 2 evolved from a single
      primordial ATPase which existed prior to the divergence of eukaryotes from
      prokaryotes. By contrast, the C-terminal segments 3 appear to be eukaryotic
      specific, are not found in similar form in any of the prokaryotic enzymes, and
      are not all demonstrably homologous among the eukaryotic enzymes. These C
      terminal domains may therefore have either arisen after the divergence of
      eukaryotes from prokaryotes or exhibited more rapid sequence divergence than
      either segment 1 or 2, thus masking their common origin. The relative rates of
      evolutionary divergence for the three segments were determined to be segment 2 <
      segment 1 < segment 3. Correlative functional analyses of the most conserved
      regions of these ATPases, based on published site-specific mutagenesis data,
      provided preliminary evidence for their functional roles in the transport
      mechanism. Our studies define the structural and evolutionary relationships among
      the P-type ATPases. They should provide a guide for the design of future studies
      of structure-function relationships employing molecular genetic, biochemical, and
      biophysical techniques.

PMID- 8151717
TI  - Organ donation in the Hispanic population: donde estan ellos?
AB  - Few studies have investigated organ donation among Hispanics, although in major
      US cities, Hispanics, like African Americans, make up a large percentage of the
      general population. In fact, the 1990 census reports that of all Hispanics in the
      country, 90% live in urban areas. The tendency for Hispanics to use hospital
      emergency rooms rather than visit a physician's office may result in an
      inadequate exchange of information between minority patients and health-care
      providers. Hospitals that serve minority populations have been reported to have
      the lowest organ procurement rates. These hospitals are often funded by local,
      county, or state funds and are usually dedicated to a patient mix that is largely
      indigent. The heavy work load of health-care providers who often have limited
      resources does not lend itself to an adequate exchange of information between
      patients and health-care providers. The existence of this type of environment
      impacts on patient communication, increases the fear of complication, and may
      diminish the discussion of potential organ procurement. There are multiple
      individual and structural reasons for the high family refusal rates among
      Hispanics. Procurement specialists may see a proportionally small number of
      Hispanic families, mainly due to a lack of referrals from hospital staff
      concerning possible Hispanic donors. White procurement workers may not be
      familiar with the Hispanic family makeup and cultural attitudes. Organ
      procurement workers may not pursue the issue of donation with Hispanic families
      as much as they do with white families. Whatever the reason, if we are to
      increase organ donation in the Hispanic community, these complex issues will need
      to be addressed.

PMID- 8151718
TI  - Politics of health-care reform.

PMID- 8151719
TI  - Race: an explanation of patient compliance--fact or fiction?
AB  - This article describes a retrospective study that examines the relationship
      between patient compliance and race among diagnosed hypertensives in the National
      Health and Nutrition Examination Survey (NHANES II). The study reviewed and
      analyzed the compliance of 403 blacks diagnosed with hypertension. Patient
      compliance was measured using the frequency that patients took their hypertensive
      medicine. Bivariate analysis revealed a statistically significant relationship
      with patient compliance (dependent) and the independent variables (age,
      education, gender, and smoking). Multiple regression for the black population
      revealed that the age of the person accounted for the most explained variance. As
      age increased among blacks, so did compliance. The results may suggest the need
      to target school-aged blacks early in order to increase the awareness and
      importance of monitoring one's blood pressure. The results also may indicate that
      race is not a marker for other characteristics (income, education, etc) that
      might be used to explain the difference in the prevalence of hypertension among
      blacks compared with whites.

PMID- 8151720
TI  - The operative and nonoperative management of blunt liver injury.
AB  - The surgical approach to liver injury depends on a clear and concise
      characterization of the wound. Blunt trauma can produce devastating wounds that
      disrupt hepatic venous drainage. Atrial caval shunting remains a useful technique
      for Grade V liver wounds. Liver packing may be necessary if diffuse lobar injury,
      acidosis, hypothermia, and coagulapathy are present. The general surgeon must
      have a wide array of surgical options that can be used for various combinations
      of injury. This article proposes that operatively identified retrohepatic
      hematomas, which remain unchanged after a period of observation, should be left
      undisturbed. Data supporting this approach, from a series of cases managed
      nonoperatively, are presented.

PMID- 8151721
TI  - A comparison of breast self-examination and clinical examination.
AB  - Twenty-six female college students were trained to examine their breasts using
      the Mammacare Method. After training, participants were asked to demonstrate
      their breast self-examination technique for a competency evaluation. On average,
      85% of the components of the palpation technique were correctly included in the
      participants' self-examinations, indicating that they had been trained
      competently. Breast self-examiners then were asked to palpate three breast models
      in search of embedded lumps. Thirteen health professionals were asked to examine
      the same breast models for lumps. The examination of the models by self-examiners
      was compared to that by health professionals. Breast self-examiners took longer
      to examine each model, and on average correctly identified significantly more
      lumps than health professionals. The two groups did not differ in number of false
      positive findings. These results indicate that women adequately trained to
      perform breast self-examination can perform breast examinations at least as
      accurately as health professionals.

PMID- 8151722
TI  - Modified bovine surfactant (Survanta) versus a protein-free surfactant (Exosurf)
      in the treatment of respiratory distress syndrome in preterm infants: a pilot
      study.
AB  - We undertook a prospective, randomized, non-blinded pilot study to determine
      whether infants with respiratory distress syndrome (RDS) who were treated with
      protein-containing bovine surfactant (Survanta, Ross/Abbott Laboratories,
      Columbus, Ohio) had earlier and larger responses in gas exchange when compared
      with similar infants treated with a synthetic surfactant (Exosurf, Burroughs
      Wellcome, Research Triangle Park, North Carolina). Forty-one infants weighing
      between 600 g and 1750 g at birth with RDS of sufficient severity to require
      assisted ventilation with an FiO2 > 0.39 were enrolled in the study and treated
      with surfactant from 1 to 8 hours after birth. Infants were randomly selected to
      receive treatment with either Exosurf or Survanta. Despite randomization, the
      Survanta group was overrepresented with factors associated with greater severity
      of RDS (lower birthweight, more males, and fewer African Americans). No
      statistically significant difference was found in the primary outcome measure
      (arterial/alveolar PaO2 > 0.3 at 24 hours) by univariate or multivariate
      analysis. The percentage of responders in the Survanta-treated group was
      significantly increased 24 hours after treatment in two of four secondary
      measures of oxygenation when analyzed by univariate tests using one-tailed P
      values. Based on these results, we anticipate that acute outcomes after Survanta
      or Exosurf will approximate those found in this trial and that differences in
      measures of oxygenation between treatment groups will approximate 30% to 50% 24
      hours after initial treatment.

PMID- 8151724
TI  - Obesity, body fat distribution, and blood pressure in Nigerian and African
      American men and women.
AB  - This article describes a study that assesses body fat distribution patterns in
      Nigerian and African-American males and females and determines the association
      between body fat distribution patterns and blood pressure in young adults of
      differing geographical and ethnic backgrounds. The study population was comprised
      of 275 African Americans (92 males and 183 females) and 282 Nigerians (219 males
      and 63 females). The mean ages for the African-American males and females were
      18.7 and 18.9 years, respectively, compared with 21 and 19.2 years for the
      Nigerian males and females. African Americans were more likely to be obese and
      overweight compared with their Nigerian counterparts. However, there were no
      significant differences between the two ethnic groups within gender for body fat
      distribution patterns based on waist-to-hip ratio. Despite being leaner, the
      Nigerians had higher diastolic blood pressures than the African Americans. There
      were no significant associations observed between blood pressure and waist-to-hip
      ratio for either the Nigerian or the African-American males or females, and body
      mass index was associated consistently with blood pressure only among the African
      Americans. These findings suggest that body mass index, a general indicator of
      obesity, is a better correlate of blood pressure than the waist-to-hip ratio
      among African Americans.

PMID- 8151723
TI  - Hearing loss: an educational and screening program for African-American and
      Latino elderly.
AB  - This article describes a study that tested the effectiveness of culturally
      sensitive educational material on hearing loss and performed mass screenings to
      evaluate the prevalence of hearing impairment among urban African-American and
      Latino seniors. Bilingual information booklets on hearing loss were mailed to
      households and senior centers in 45 census tracts with high concentrations of
      minority elderly. Seniors were invited for hearing evaluations and were screened
      using a handheld audioscope. Subjects with hearing impairment were referred for
      specialized testing and later telephoned to assess subsequent care. Four hundred
      thirty-three persons (3.14%) responded to three mailings, typically by presenting
      for a hearing evaluation. Responses to a brief questionnaire indicated a high
      degree of learning about hearing loss. Of the 296 seniors screened, 174
      demonstrated abnormal hearing, but only 26% obtained further testing. Barriers to
      follow-up care included problems with finances, transportation, and illness.

PMID- 8151725
TI  - Langerhans' cell histiocytosis associated with Hodgkin's disease: a case report.
AB  - A patient who developed pulmonary Langerhans' cell histiocytosis after
      chemotherapy for nodular sclerosing Hodgkin's disease is presented. Twenty-one
      cases of Langerhans' cell histiocytosis associated with Hodgkin's disease have
      been reported in the literature. Such an association seems to be more than
      fortuitous. The possibilities of a common etiological agent inducing both
      Hodgkin's disease and Langerhans' cell histiocytosis and of a reactive
      proliferation of Langerhans' cells after radiotherapy or chemotherapy for
      Hodgkin's disease are discussed.

PMID- 8151726
TI  - Condom misuse among adolescents.

PMID- 8151727
TI  - In vitro and in vivo characterisation of glial cells immortalised with a
      temperature sensitive SV40 T antigen-containing retrovirus.
AB  - An oncogene-carrying replication-defective retrovirus was used to establish
      immortalised lines of murine glial cells. Primary cultures of early postnatal
      cerebellar cells were infected with a retrovirus based on the Murine Moloney
      Leukemia Virus containing a temperature-sensitive mutant of the Simian Virus 40
      large T antigen (SV40 T) oncogene and a gene coding for resistance to the
      antibiotic G418. Infected cells were selected in G418 and after several in vitro
      passages cells expressing the O4 antigen were established as a cell line. At a
      later time point O4-positive single-cell clones were established. Two different
      types of clones were obtained: 1) "plastic" clones consisting of cells which
      initially had a morphological and antigenic phenotype of young glial precursor
      cells but which gradually lost these features, and 2) "stable" cell clones
      including a clone with the immunological and electrophysiological characteristics
      of Schwann cells. Culture of the latter cells in the presence of 1 mM dibutyryl
      cyclic adenosine monophosphate for a period of at least 10 days induced a change
      in shape and a shift in antigen expression towards a more "differentiated"
      maturation stage. When the SV40 T O4-positive immortalised cell line isolated on
      the cell sorter was transplanted into demyelinated lesions in adult rats, cells
      were observed ensheathing axons and forming limited amounts of PNS-type myelin.
      Glial cells immortalised with a temperature-sensitive mutant of the SV40 T
      oncogene thus retain many physiological properties of their primary culture
      counterparts and can be induced to undergo limited differentiation in vitro and
      in vivo. These cell lines, which represent immature CNS glia or Schwann cells,
      are providing useful tools for investigating the role of cell surface antigens
      involved in neuron-glial interactions.

PMID- 8151728
TI  - Secretion of amyloid precursor protein and laminin by cultured astrocytes is
      influenced by culture conditions.
AB  - Although normally quiescent, astrocytes in the adult brain respond to various
      types of brain injury by rapidly dividing, swelling, extending cellular
      processes, and expressing increased amounts of glial fibrillary acidic protein
      (GFAP). These phenomena are collectively referred to as "astrogliosis."
      Similarly, astroglia in primary culture stop dividing when they attain
      confluency, yet, as seen in situ, they retain their proliferative capacity for
      extended periods and resume rapid division when subcultured. To examine the
      impact of glial division on secretion of neurite-promoting factors, conditioned
      medium (CM) was removed from subconfluent, newly confluent, and long-term
      confluent ("aged") neonatal rat astrocyte cultures, and from aged confluent
      cultures that had been repassaged, "lesioned" (scraping with a rubber policeman),
      or triturated 3 days before harvest. Secretion of neurite-promoting factor(s) by
      glial cells into these CM was then assayed by treating neuroblastoma cultures
      with these various CM and quantitating neurite elaboration. Extensive neurite
      sprouting was elicited by CM from cultures just reaching confluency and from
      repassaged, lesioned, or triturated cultures. CM from aged confluent cultures did
      not induce sprouting. These results indicate that secretion of neurite-promoting
      factor(s) is regulated by glial division, and suggest that gliosis in situ may
      contribute to neurite sprouting by similar mechanisms. Immunoblot analysis
      demonstrated the presence in CM of varying amounts of laminin and amyloid
      precursor protein (APP), including isoforms containing the Kunitz-type protease
      inhibitor domain. CM from subconfluent cultures contained trace amounts of these
      proteins, but CM from cultures just reaching confluency contained significant
      amounts. Although CM from aged cultures contained barely detectable levels of
      either protein, trituration or repassage of aged cultures dramatically increased
      secretion of these proteins. APP- and laminin-enriched CM fractions promoted
      neuritogenesis to a similar level as respective unfractionated CM; anti-APP and
      anti-laminin antisera blocked this effect. Purified human brain APP promoted
      neuritogenesis when added to non-conditioned medium and aged CM. Increased
      secretion of APP and laminin therefore mediates at least a portion of CM-induced
      neuronal sprouting; these proteins may perform analogous functions during
      astrogliosis in situ.

PMID- 8151729
TI  - Leukemia inhibitory factor prevents the death of axotomised sensory neurons in
      the dorsal root ganglia of the neonatal rat.
AB  - Leukemia inhibitory factor (LIF) has several characteristics of a neurotrophic
      factor for sensory neurons. Here we have investigated whether LIF also supports
      the survival of axotomised sensory neurons in vivo. Newborn rat pups received a
      unilateral sciatic nerve transection and the injury site was treated with gelfoam
      soaked in phosphate buffered saline (PBS), nerve growth factor (NGF), or LIF.
      Neuronal nucleoli in the L5 dorsal root ganglia were counted, appropriate
      corrections applied, and the resultant neuronal loss expressed as a percentage of
      the contralateral intact side. In animals where LIF was administered neuronal
      loss was significantly reduced: 2 days after LIF treatment neuronal loss was
      19.5% compared to 43% in PBS-treated animals; 3 days after LIF treatment neuronal
      loss was 20.4% compared to 40.2% in PBS-treated animals; however, 7 days after
      LIF treatment there was no significant reduction in the number of neurons lost.
      The degree of rescue of sensory neurons in vivo by LIF was found to be similar to
      NGF, which was not surprising as both factors supported the survival of a similar
      population of sensory neurons in vitro. Rescue was not observed when LIF
      containing gelfoam was placed away from the axotomised nerve, suggesting that
      LIF's action may be associated with its retrograde transport or direct signalling
      at the site of nerve injury.

PMID- 8151730
TI  - Distribution and differentiation of A2B5+ glial precursors in the developing rat
      spinal cord.
AB  - In many regions of the rat central nervous system, oligodendrocytes develop from
      migratory A2B5+ precursor cells. In the rat spinal cord, during early embryonic
      development the capacity for oligodendrogenesis appears to be restricted to
      ventral regions of the spinal cord, while cultures of postnatal rat spinal cord
      contain a distinct population of A2B5+ astrocyte precursors. To determine if, as
      in other regions of the CNS, spinal cord A2B5+ cells give rise directly to
      oligodendrocytes and astrocytes, the initial distribution, and subsequent
      dispersion, proliferation, and differentiation of spinal cord A2B5+ cells have
      been examined in both explant and dissociated cell cultures. Spinal cord
      oligodendrocytes develop from A2B5+ cells. At E14, A2B5+ cells are restricted to
      ventral regions of the spinal cord and as development proceeds they become more
      uniformly distributed throughout the spinal cord. In explant cultures, greater
      than 95% of the explants that contain oligodendrocytes also contain A2B5+ cells
      and a proportion of mature oligodendrocytes retain detectable A2B5
      immunoreactivity briefly on their surface. The maturation of spinal cord
      oligodendrocyte precursors occurs in a number of distinct stages characterized by
      the expression of O4 immunoreactivity, which first appears at E16, and GC
      immunoreactivity, which first appears at E18. As spinal cord oligodendrocyte
      precursors acquire O4 immunoreactivity they appear to lose the ability to
      proliferate in response to PDGF but retain the ability to proliferate in response
      to bFGF, suggesting that the control of proliferation of oligodendrocyte
      precursors is, in part, dependent on their maturational state. In the presence of
      high serum, spinal cord A2B5+ cells fail to develop in isolated E14 dorsal spinal
      cord cultures, while in ventral cultures they subsequently differentiate into
      A2B5+ astrocytes suggesting that A2B5+ astrocyte precursors are also initially
      ventrally located. Unlike oligodendrocyte differentiation, however, the
      differentiation of spinal cord A2B5+ cells into astrocytes is delayed in early
      embryonic-derived cultures compared to those from older animals. These
      observations suggest that local influences may regulate the timing of spinal cord
      A2B5+ astrocyte development, but not spinal cord oligodendrocyte development.

PMID- 8151731
TI  - Satellite cells in slow and fast rat muscles differ in respect to
      acetylcholinesterase regulation mechanisms they convey to their descendant
      myofibers during regeneration.
AB  - The hypothesis of satellite cell diversity in slow and fast mammalian muscles was
      tested by examining acetylcholinesterase (AChE) regulation in muscles
      regenerating 1) under conditions of muscle disuse (tenotomy, leg immobilization)
      in which the pattern of neural stimulation is changed, and 2) after cross
      transplantation when the regenerating muscle develops under a foreign neural
      stimulation pattern. Soleus (SOL) and extensor digitorum longus (EDL) muscles of
      the rat were allowed to regenerate after ischemic-toxic injury either in their
      own sites or had been cross-transplanted to the site of the other muscle.
      Molecular forms of AChE in regenerating muscles were analyzed by velocity
      sedimentation in linear sucrose gradients. Neither tenotomy nor limb
      immobilization significantly affected the characteristic pattern of AChE
      molecular forms in regenerating SOL muscles, suggesting that the neural
      stimulation pattern is probably not decisive for its induction. During an early
      phase of regeneration, the general pattern of AChE molecular forms in the cross
      transplanted regenerating muscle was predominantly determined by the type of its
      muscle of origin, and much less by the innervating nerve which exerted only a
      modest modifying effect. However, alkali-resistant myofibrillar ATPase activity
      on which the separation of muscle fibers into type I and type II is based, was
      determined predominantly by the motor nerve innervating the regenerating muscle.
      Mature regenerated EDL muscles (13 weeks after injury) which had been innervated
      by the SOL nerve became virtually indistinguishable from the SOL muscles in
      regard to their pattern of AChE molecular forms. However, AChE patterns of mature
      regenerated SOL muscles that had been innervated by the EDL nerve still displayed
      some features of the SOL pattern. In regard to AChE regulation, muscle satellite
      cells from slow or fast rat muscles convey to their descendant myotubes the
      information shifting their initial development in the direction of either slow or
      fast muscle, respectively. The satellite cells in fast or slow muscles are,
      therefore, intrinsically different. Intrinsic information is expressed mostly
      during an early phase of regeneration whereas later on the regulatory influence
      of the motor nerve more or less predominates.

PMID- 8151732
TI  - Cholinergic markers are expressed in developing and mature neurons of chick
      dorsal root ganglia.
AB  - The presence of acetylcholinesterase has been reported in chick dorsal root
      ganglia at early developmental stages although acetylcholine is not known to play
      a role in these ganglia. Recently, we reported that during development the level
      of acetylcholinesterase increases continuously and the enzyme becomes gradually
      expressed in all sensory neurons. These observations prompted the study of the
      developmental pattern of expression of other cholinergic markers, such as choline
      acetyltransferase (ChAT) and the high affinity transport mechanism for choline.
      ChAT activity is barely detectable at early developmental stages (E7) and
      increases markedly thereafter, with an activity profile similar to that described
      for acetylcholinesterase. A similar increase in enzyme activity is also observed
      when ChAT is measured in dorsal root ganglia explants and in dissociated cells in
      culture. The study of ChAT activity in cultured cells shows an increase over a
      period of 3 days, thus ruling out the hypothesis that motor fibers, still
      associated to the ganglia, may represent a possible source of the enzyme.
      Immunostaining of whole ganglia or cultured cells shows that ChAT
      immunoreactivity is not restricted to a specific neuronal sub-population but
      appears as a common marker of sensory neurons. High affinity choline uptake,
      blocked by hemicholinium, is present in sensory neurons cultured from E7 dorsal
      root ganglia. Observations on cultured neurons from later stages (E18) indicate
      that choline transport is not a transient property of sensory neurons. These
      observations show a similar pattern of expression of several cholinergic markers
      during development. Such a pattern is maintained at significant levels also in
      mature ganglia.

PMID- 8151733
TI  - Glia-derived nexin/protease nexin-1 is expressed by a subset of neurons in the
      rat brain.
AB  - Glia-derived nexin/protease nexin-1 (GDN/PN-1) is a serine protease inhibitor
      that is secreted by glial cells and fibroblasts in culture. In the adult
      mammalian nervous system it has been shown to be expressed in the olfactory
      system and by some glial cells in response to neuronal injury. In situ
      hybridization and immunocytochemical studies were performed to identify the
      structures expressing GDN/PN-1 in the developing and adult rat brain. In contrast
      to a transient widespread expression during pre- and postnatal development, some
      brain structures constitutively express GDN/PN-1. These include the olfactory
      nerve layer of the olfactory bulb, basal forebrain, striatum, pyramidal neurons
      of layer V in the cortex, thalamic nuclei, pars compacta of the substantia nigra,
      inferior and superior colliculi, and deep cerebellar nuclei. All of these parts,
      excluding the olfactory nerve layer, are characterized by a high neuronal cell
      density. Neurons in these regions were immunoreactive for GDN/PN-1. Furthermore
      GDN/PN-1 expression in cell lines showed that the active protein was synthesized
      and secreted from B104 but not from NB2a neuroblastoma cells. Although GDN/PN-1
      has only been reported to be synthesized by glia, the results presented here
      demonstrate that in addition, a subset of neurons express this protease
      inhibitor.

PMID- 8151734
TI  - Induction of glioma cell death by 1,25(OH)2 vitamin D3: towards an endocrine
      therapy of brain tumors?
AB  - The secosteroid 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3) is the major biologically
      active metabolite of vitamin D. Antitumor activity of this hormone has been
      observed on several cell lines and on breast cancer in vivo. The purpose of this
      in vitro study was to determine the possible effect of 1,25(OH)2D3 on glioma
      cells. Two glioma cell lines from rat (C6) or human (GHD) origin were cultured in
      the presence of 1,25(OH)2D3. The sensitivity of these cells to 1,25 (OH)2D3 was
      assessed with a colorimetric MTT assay. A cytotoxic effect of 1,25(OH)2D3 was
      detected at concentrations around 10(-8) M. A lag period of 3 days was required
      between the onset of the treatment and the observation of the effects. However,
      the continuous presence of 1,25(OH)2D3 is not required since cell death occurred
      even when C6 cells were challenged for 24 hr with 1,25(OH)2D3 and then cultured
      in the absence of the hormone. In addition, 1,25(OH)2D3 regulates the expression
      of its own receptors in C6 glioma. These results provide to our knowledge the
      first evidence for a cytotoxic effect of 1,25(OH)2D3 on rat and human glioma
      cells and could offer both an experimental model to study a programmed cell death
      in a brain-derived cell line and a new strategy for the inhibition of glioma
      growth in vivo.

PMID- 8151735
TI  - Experimental studies on prevention of atherosclerotic arterial stenosis and
      restenosis after angioplasty with Andrographis Paniculata Nees and fish oil.
AB  - In order to search for effective drugs to reduce restenosis incidence after
      coronary angioplasty, we studied the effects of a Chinese herb, extract of
      Andrographis Paniculata Nees (APN), and Fish Oil (FO) on atherosclerotic stenosis
      and restenosis after experimental angioplasty. Preliminary results showed that
      APN can significantly alleviate atherosclerotic iliac artery stenosis induced by
      both deendothelialization and high cholesterol diet (control group, stenosis
      incidence 100%, stenotic severe degree 60.53 +/- 31.03%, of which 30% arteries
      (6) are total occlusion; FO group: stenotic incidence and severe degree are 77%
      and 53.00 +/- 21.17%, respectively, and in APN group they are 70% and 25.39 +/-
      10.52%, respectively, P < 0.01), and follow-up angiography 4 weeks after
      angioplasty showed that dilated iliac arteries in control group all had severe
      restenosis, but in APN group no or only mild restenosis occurs, and in FO group
      restenosis is as severe as stenotic degree prior to angioplasty. These
      preliminary results suggest that APN and FO can significantly alleviate stenosis
      induced by deendothelialization and high cholesterol diet and restenosis after
      angioplasty, while the former has a more marked effect. The above findings lead
      the authors to conclude that APN may play an important role in preventing
      restenosis after coronary angioplasty, but FO may be useful in reducing the
      extent of of restenosis after coronary angioplasty.

PMID- 8151736
TI  - Effects of tetrahydroberberine on isoproterenol-stimulated mitochondrial 45Ca
      uptake in rabbit myocardia.
AB  - Cardiac mitochondria of rabbit was prepared by differential centrifugation.
      Tetrahydroberberine (THB) 10 mumol/L inhibited isoproterenol 1 mumol/L induced
      45Ca uptake in the mitochondria by 48.58%. The inhibition is concentration
      dependent and may play an important role in the protection of mitochondrial
      function in cardiac ischemia and reperfusion injury.

PMID- 8151737
TI  - Effect of intracerebroventricular injection of 6-hydroxydopamine on the
      peripheral catecholamine and angiotensin II in SHR.
AB  - This investigation revealed that the contents of A II and NE in plasma, heart and
      aorta and E content in plasma were significantly increased in SHR at the age of
      12th week. At the same time the systolic blood pressure of SHR was much higher
      than that of the age-matched WKY. The intracerebroventricular administration of 6
      OHDA in SHR at the age of 8th week not only prevented the development of
      hypertension, but also reduced the contents of NE and E in the brain regions,
      heart, aorta and plasma. Simultaneously A II content in heart, aorta and plasma
      was decreased. These results suggested that: 1. the renin-angiotensin system and
      peripheral sympatho-adrenal system are overactive in SHR, 2. the overactivity of
      peripheral sympatho-adrenal system is dependent on the central catecholaminergic
      neurons, and 3. the action of sympatho-adrenal system is partly responsible for
      the increase of A II content in plasma, heart and aorta in SHR.

PMID- 8151738
TI  - Use of fluorescent substrate 4-MUP in the detection of biotin-labeled DNA probes.
AB  - To improve the sensitivity of detecting biotin-labeled DNA Probes, a new
      fluorescent substrate of alkaline phosphatase, 4-methylum belliferylphosphate (4
      mup) was studied instead of conventional BCIP-NBT. The result of dot-blot
      hybridization demonstrates that this new substrate can be used for the
      colorimetric detection of biotin-labeled probes after hybridization to
      immobilized nucleic acids. The sensitivity is about one order of magnitude higher
      than that of BCIP-NBT system, and the time required for color development is very
      short, only about five min. It is suggested that the Bio-SA-Bio-AP-4-MUP
      colorimetric detection system can be widely used in gene diagnosis.

PMID- 8151739
TI  - Studies on monoclonal anti-isotypic and anti-idiotypic antibodies against
      leukemia and myeloma: VI. Purification and relative affinity of monoclonal
      antibodies.
AB  - In this study, the anti-idiotypic and anti-isotypic antibodies (McAbs) against
      IgM of the Patient with B chronic lymphocytic leukemia (B-CLL) were purified from
      hybridoma ascites by n-Octoic acid precipitation method. The purified McAbs have
      high purify and high antibody activity as evidenced by immunoelectrophoresis, SDS
      PAGE and ELISA. Relative affinity of 11 McAbs was measured by using indirect
      ELISA and double antibody sandwich ELISA method. It was found that relative
      affinity of various McAbs to the same antigen was different. 11 McAbs could be
      divided into two groups by analysing their 50% maximum binding. The relative
      affinity of 4 McAbs in the culture supernatants was consistent with that of McAbs
      in the purified ascites. Our experimental results provide an important basis for
      rational application of these McAbs.

PMID- 8151740
TI  - Clinical and prognostic investigations on M2/t(8;21) acute nonlymphocytic
      leukemia.
AB  - Clinical and prognostic investigations were conducted in 46 cases of M2/t(8;21)
      leukemia and 29 cases of M2/NN patients. Results showed that most patients with
      M2/t(8;21) were young males with higher incidence of extramedullary
      infiltrations. Complete remission rate was higher but with earlier relapse. The
      prognosis of patients with M2/t(8;21) with loss of one sexual chromosome was
      poor.

PMID- 8151741
TI  - Dynamic observations on NK cell activity and IL-2 and IFN gamma production in
      vitro in patients on maintenance hemodialysis.
AB  - In order to study the immune function of patients on maintenance hemodialysis
      (MHD), we assayed NK cell cytotoxicity against K562 targets in 40 patients on
      MHD, and the production of IL-2 and IFN in peripheral blood mononuclear cells
      (PBMC) after PHA stimulation, in contrast to those in normal controls. The
      results showed that NK cell activity and IL-2 and IFN levels were markedly lower
      in the patients than in the controls. After a single dialysis, NK cell activity
      as well as IL-2 and IFN levels were elevated to different extent. But there was
      no significant change in patients after long-term dialysis. There was a positive
      correlation between the NK cell activity and IL-2 and IFN activity in the
      controls, but no such correlation was found in the patients on MHD. There was a
      positive correlation between the NK cell activity and IL-2 activity in patients
      after dialysis, suggesting that immune function were impaired in the patients on
      MHD, with a decline in the activity of NK cell and IL-2 and IFN, and a disorder
      of immune regulation cycle. These abnormal immune impairments in the patients
      could be partly corrected by hemodialysis. However, long-term hemodialysis is not
      much helpful in the improvement of patient's immune function.

PMID- 8151742
TI  - Measurement of platelet-activating factor in human blood by high performance thin
      layer chromatography and its clinical application.
AB  - Platelet-activating factor (PAF) present in the blood of the patients with
      chronic pulmonary heart disease and asthma has been detected by high performance
      thin layer chromatography (HPTLC). The patients with chronic pulmonary heart
      disease accompanied by carbon dioxide retention (PaCO2 > 6.67 kPa) have a higher
      level of PAF in blood (0.75 +/- 0.27 microgram/ml) than those who have no carbon
      dioxide retention (PaCO2 < 6.67 kPa, PAF 0.41 +/- 0.25 microgram/ml) and those in
      the normal control group (0.45 +/- 0.20 microgram/ml), with P < 0.05 in all. The
      patients with asthma have a higher PAF in blood (0.83 +/- 0.05 microgram/ml) than
      those in the control group (P < 0.005). These findings suggest that PAF plays an
      important role in episodes of chronic pulmonary heart disease and asthma.

PMID- 8151743
TI  - Effect of cardiopulmonary bypass on the specific immunity of the host.
AB  - T cell subsets and immunoglobulin (Ig) were observed sequentially with the OKT
      monoclonal antibodies rosette test and the rate scattering turbidimetry in 13
      patients who underwent open heart surgery under cardiopulmonary bypass (CPB) for
      rheumatic heart diseases (RHD) and congenital heart diseases (CHD), before and
      after operation. Compared with preoperative values, in the early period after
      CPB, T helper cells, T helper cells to T suppressor cells ratio and IgG decreased
      significantly; whereas T suppressor cells increased, in RHD and CHD. The T cell
      subsets returned to the preoperative levels two weeks after CPB in RHD and CHD.
      The IgG came back to the preoperative levels two weeks after CPB in RHD and only
      one week after CPB in CHD.

PMID- 8151744
TI  - Variation of haemorheological parameters in renal and pancreatic rejection.
AB  - Abnormalities of haemorheology were found in animal and human recipients of
      kidney and/or pancreas allografts during rejection episodes. Thirteen diabetic
      canines received solitary pancreatic transplantation and another 13 diabetic and
      uremic canines underwent combined pancreas and kidney transplantation.
      Determination of haemorheological parameters was performed before and after
      operation respectively. During rejection episodes of kidney or pancreas
      allografts, the values of plasma viscosity, blood reductive viscosity and
      fibrinogen were significantly higher than those without rejection. On the basis
      of animal experiments, the determination of haemorheological parameters had been
      performed on 33 patients (30 receiving renal transplant, 2 pancreatic transplant
      alone and the remaining 1 combined renal and pancreatic transplant). Consecutive
      monitoring on these patients showed that a rise in the values of plasma
      viscosity, blood reductive viscosity and fibrinogen could be demonstrated during
      rejection episodes. The changes appeared one to three days prior to clinical
      manifestations and were in accordance with the termination of rejection. Our
      studies suggest that variation of haemorheological parameters are associated with
      rejection and the abnormal haemorheology may be an essential factor contributing
      to graft dysfunction. Moreover, the use of these assays will be beneficial to
      early diagnosis and better management of rejection in the future.

PMID- 8151745
TI  - Rupture of thoracic aortic aneurysm into the lung with formation of
      pseudoaneurysm: diagnosis and treatment.
AB  - Three patients with rupture of thoracic aortic aneurysm into the lung with
      formation of pseudoaneurysm were admitted to our hospital in 1991, of whom, 2 had
      ascending aortic aneurysms which ruptured into the right upper pulmonary lobe,
      and another one had descending aortic aneurysm rupturing into the left upper
      lobe. All 3 cases were misdiagnosed as having pulmonary carcinoma or mediastinal
      tumor by the other hospital as well as by us. Correct diagnosis was made by
      aortography or at exploratory thoracotomy. Our preliminary experiences in the
      diagnosis and treatment of the disease are presented in this paper.

PMID- 8151746
TI  - An ultrastructural observation of macrophages in rabbits' radius callus.
AB  - The ultrastructure of macrophages in rabbits' radius callus at the 14th and 31st
      day after fracture had been observed in the study. It was found that macrophages
      mostly appeared in the early stage callus where there were inflammation, clot,
      and bone chips. Commonly seen macrophages were active phagocytes with single
      nucleus, but they could evolve to form multinuclear macrophages or fuse into
      foreign body giant cells. We are therefore led to conclude that the functions
      performed by macrophages in healing callus are to phagocytize and digest damaged
      cellular fragments, small bone chips, clot and foreign body; to disrupt larger
      dead bone matrix extracellularly and to resorb them by microvilli-like processes
      on the surface of foreign body giant cells.

PMID- 8151747
TI  - Correlative factors of left ventricular hypertrophy in end-stage renal disease.
AB  - The correlative factors of left ventricular hypertrophy (LVH) in 287 end-stage
      renal disease (ESRD), admitted from 1983 to 1992, were analyzed. 52% of patients
      had LVH including 54% of patients on hemodialysis, 75% of patients with
      peritoneal dialysis and 38% of transplanted patients. Single factor analysis
      indicated that age, blood pressure, serum creatinine and BUN, hemoglobin, serum
      alkaline phosphatase, aortic valve disease and present DSRD therapy were related
      to LVH. Multiple logistic regression analysis indicated that the most important
      factors which independently related to LVH in all patients studied, were
      management of present ESRD treatment, age, hypertension and high serum alkaline
      phosphatase. In a subset of patients with severe LVH, high serum alkaline
      phosphatase level, high systolic blood pressure and age were the predictive
      factors. In patients on dialysis, the most important variable were age and high
      serum alkaline phosphatase. Hypertension was the sole predictor of LVH in the
      transplant group.

PMID- 8151748
TI  - Focal infection revisited.

PMID- 8151749
TI  - Chimeric Theiler's virus with altered tropism for the central nervous system.
AB  - Theiler's virus is a neurotropic murine picornavirus which, depending on the
      strain, causes either an acute encephalitis or a persistent demyelinating
      disease. Following intracranial inoculation, the demyelinating strains infect
      sequentially the grey matter of the brain, the grey matter of the spinal cord,
      and finally the white matter of the spinal cord, where they persist and cause
      chronic demyelination. The neurovirulent strains cause a generally fatal
      encephalitis with lytic infection of neurons. The study of chimeric Theiler's
      viruses, obtained by recombining the genomes of demyelinating and neurovirulent
      strains, has shown that the viral capsid contains determinants for persistence
      and demyelination. In this article we describe the recombinant virus R5, in which
      the capsid protein VP1 and a small portion of protein 2A come from the
      neurovirulent GDVII strain and the rest of the genome comes from the persistent
      DA strain. The capsid of virus R5 also contains one mutation at amino acid 34 of
      VP3 (Asn-->His). Virus R5 does not persist in the central nervous system (CNS) of
      immunocompetent SJL/J or BALB/c mice. However, it replicates efficiently and
      persists in the CNS of BALB/c nu/nu mice, showing that its growth in the CNS is
      not impaired. In BALB/c nu/nu mice, whereas virus DA causes mortality with large
      amounts of viral antigens in the white matter of the spinal cord, virus R5 does
      not kill the animals, persists in the neurons of the grey matter of the brain,
      and never reaches the white matter of the spinal cord. This phenotype is due to
      the chimerism of the capsid and/or to the mutation in VP3. These results indicate
      that the capsid plays an important role in the characteristic migration of
      Theiler's virus within the CNS.

PMID- 8151750
TI  - Spontaneous fusions to prv43 can suppress the export defect of pseudorabies virus
      gIII signal peptide mutants.
AB  - We have devised an enrichment scheme for the isolation of export-competent
      derivatives of pseudorabies virus glycoprotein gIII signal peptide mutants.
      Enrichment is based upon a growth advantage imparted upon gIII-containing virions
      compared with virions lacking the glycoprotein. Each of identified derivatives
      suppressed the gIII signal peptide defect by fusing the gIII gene in frame to the
      prv43 gene that lay immediately upstream; the result was the synthesis of a Prv43
      gIII hybrid protein. The deduced Prv43 protein is predicted to span a membrane
      multiple times, and it appeared that the gIII portion of each hybrid used a
      hydrophobic domain of Prv43 protein to initiate its export. For at least two of
      the isolates, the hybrid protein was efficiently translocated across the
      endoplasmic reticulum membrane but appeared to be poorly exported out of the
      endoplasmic reticulum. Nonetheless, the prv43-gIII fusions encoded a gIII species
      that was localized to the virus envelope. Because the gIII portion of each hybrid
      protein must be exposed on the virion surface to provide a growth advantage, our
      results also suggest a preliminary membrane topology for wild-type Prv43 protein.

PMID- 8151751
TI  - Identification of domains in bluetongue virus VP3 molecules essential for the
      assembly of virus cores.
AB  - Bluetongue virus (BTV) cores consist of the viral genome and five proteins,
      including two major components (VP3 and VP7) and three minor components (VP1,
      VP4, and VP6). VP3 proteins form an inner scaffold for the deposition on the core
      of the surface layer of VP7. VP3 also encapsidates and interacts with the three
      minor proteins. The BTV VP3 protein consists of 901 amino acids and has a
      sequence that is a highly conserved among BTV serotypes and other orbiviruses
      (e.g., epizootic hemorrhagic disease virus and African horse sickness virus). To
      locate sites of interaction between VP3 and the other structural proteins, we
      have analyzed the effects of a number of VP3 deletion mutants representing
      conserved regions of the protein, using as an assay the formation of core-like
      particles (CLPs) expressed by recombinant baculoviruses. Five of the VP3 deletion
      mutants interacted with the coexpressed VP7 and made CLPs. These CLPs also
      incorporated the three minor proteins. One mutant, lacking VP3 amino acid
      residues 499 to 508, failed to make CLPs. Further mutational analyses have
      demonstrated that a methionine at residue 500 of VP3 and an arginine at residue
      502 were both required for CLP formation.

PMID- 8151752
TI  - Reversible repression of papillomavirus oncogene expression in cervical carcinoma
      cells: consequences for the phenotype and E6-p53 and E7-pRB interactions.
AB  - The transforming genes E6 and E7 of high-risk human papillomaviruses are
      consistently expressed in papillomavirus-associated neoplasms of the anogenital
      tract. In papillomavirus type 18-associated SW 756 cervical carcinoma cells,
      transcription of the viral E6-E7 genes is blocked by dexamethasone. Herein we
      show that dexamethasone-mediated repression of the E6-E7 genes results in loss of
      the neoplastic phenotype of SW 756 cells. Withdrawal of dexamethasone restores E6
      E7 expression and neoplastic growth. Moreover, reconstitution of E6-E7 gene
      expression by a dexamethasone-inducible expression vector renders the neoplastic
      phenotype resistant to dexamethasone. These results clearly indicate that the
      continuous expression of the viral E6-E7 oncogenes is required to maintain the
      neoplastic growth properties of SW 756 cervical cancer cells. The viral E6
      protein destabilizes the p53 tumor suppressor gene product in vitro. Since low
      levels of p53 have been observed in papillomavirus-transformed keratinocyte cell
      lines, it was speculated that degradation of p53 by E6 contributes to
      papillomavirus-associated growth deregulation. Consistent with this hypothesis,
      we detected a significant increase in p53 levels upon dexamethasone-induced
      repression of papillomavirus E6-E7 oncogene expression. No p53 increase was
      observed in dexamethasone-treated cells in which the viral oncogene expression
      was restored. The viral E7 protein has been shown to complex with the
      retinoblastoma tumor suppressor gene product (pRB). In some cells, this
      interaction has been shown shown to release the transcription factor E2F from its
      complex with pRB, and it has been hypothesized that E7-induced, increased levels
      of free E2F contribute to the transforming potential of the viral oncogenes. In
      gel shift experiments, we detected relatively stable complexes of pRB and E2F in
      all SW 756-derived cells, independent of the level of E7 expression. This
      suggests that E7-mediated release of E2F from its complex with pRB might not be
      required to maintain the neoplastic phenotype of human papillomavirus-associated
      cancer cells, although a possibly relevant partial E7-mediated release of E2F
      from pRB cannot be excluded.

PMID- 8151753
TI  - Human cytomegalovirus-infected cells have unstable assembly of major
      histocompatibility complex class I complexes and are resistant to lysis by
      cytotoxic T lymphocytes.
AB  - Viruses which cause persistence in the naturally infected host are predicted to
      have evolved immune evasion mechanisms. Human cytomegalovirus (HCMV) causes
      significant morbidity and mortality in immunocompromised patients yet persists
      without clinical manifestations in seropositive individuals who have normal
      immune function. We report that HCMV infection in vitro impairs major
      histocompatibility complex class I (MHC-I) assembly accompanied by resistance to
      killing by cytotoxic CD8+ T lymphocytes. Pulse-chase metabolic labelling
      experiments show that MHC-I complexes continue to be assembled by both uninfected
      and HCMV-infected cells. However, MHC-I molecules are unstable in HCMV-infected
      cells and are rapidly broken down. Endoglycosidase H treatment of
      immunoprecipitates indicates that the breakdown of MHC-I complexes in HCMV
      infected cells occurs primarily in a pre-Golgi compartment. Interference with
      normal MHC-I assembly and expression, if relevant in vivo, may have implications
      for the restriction of the diversity of the CD8+ cytotoxic T lymphocyte
      repertoire directed against HCMV antigens and may be an important mechanism of
      viral persistence.

PMID- 8151754
TI  - A herpes simplex virus 1 US11-expressing cell line is resistant to herpes simplex
      virus infection at a step in viral entry mediated by glycoprotein D.
AB  - A baby hamster kidney [BHK(tk-)] cell line (US11cl19) which stably expresses the
      US11 and alpha 4 genes of herpes simplex virus 1 strain F [HSV-1(F)] was found to
      be resistant to infection with HSV-1. Although wild-type HSV-1(F) attached with
      normal kinetics to the surface of US11cl19 cells, most cells showed no evidence
      of infection and failed to accumulate detectable amounts of alpha mRNAs. The
      relationship between the expression of UL11 and resistance to HSV infection in
      US11cl19 cells has not been defined, but the block to infection with wild-type
      HSV-1 was overcome by exposing cells with attached virus on their surface to the
      fusogen polyethylene glycol, suggesting that the block to infection preceded the
      fusion of viral and cellular membranes. An escape mutant of HSV-1(F), designated
      R5000, that forms plaques on US11cl19 cells was selected. This mutant was found
      to contain a mutation in the glycoprotein D (gD) coding sequence that results in
      the substitution of the serine at position 140 in the mature protein to
      asparagine. A recombinant virus, designated R5001, was constructed in which the
      wild-type gD gene was replaced with the R5000 gD gene. The recombinant formed
      plaques on US11cl19 cells with an efficiency comparable to that of the escape
      mutant R5000, suggesting that the mutation in gD determines the ability of the
      mutant R5000 to grow on US11cl19 cells. The observation that the US11cl19 cells
      were slightly more resistant to fusion by polyethylene glycol than parental
      BHK(tk-) cells led to the selection and testing of clonal lines from unselected
      and polyethylene glycol-selected BHK(tk-) cells. The results were that 16% of
      unselected to as much as 36% of the clones selected for relative resistance to
      polyethylene glycol fusion exhibited various degrees of resistance to infection.
      The exact step at which the infection was blocked is not known, but the results
      illustrate the ease of selection of cell clones with one or more sites at which
      infection could be blocked.

PMID- 8151755
TI  - Multiple cellular factors bind to cis-regulatory elements found inboard of the 5'
      palindrome of minute virus of mice.
AB  - Previous genetic analysis of the DNA replication of minute virus of mice (MVM)
      minigenomes suggested that specific elements, A (nucleotides [nt] 4489 to 4636)
      and B (nt 4636 to 4695), found inboard of the 5' palindrome are required for
      efficient MVM DNA replication (P. Tam and C. R. Astell, Virology 193:812-824,
      1993). In this report, we show that two MVM RsaI restriction fragments (RsaI A
      [nt 4431 to 4579] and RsaI B [nt 4579 to 4662]) are able to activate DNA
      replication of an MVM minigenome containing deletions of both elements A and B.
      We also show that sequences inboard of the right palindrome are able to activate
      replication of minigenomes containing two left termini. In order to investigate
      the importance of the RsaI fragments, we demonstrate the presence of a number of
      sequence-specific DNA-protein interactions by electrophoretic mobility shift
      assays. After partial fractionation of A9 nuclear extracts, DNase I footprinting
      analysis was used to determine the binding sites for MVM replication factor (MRF)
      B5. MRF B5 protects two distinct regions (sites I and II) of the RsaI B probe
      from DNase I digestion. Competition f electrophoretic mobility shift assays with
      synthetic oligonucleotides corresponding to sites I and II suggest that MRF B5 is
      composed of two factors, MRF B3 and MRF B4, which bind DNA independently in a
      sequence-specific manner. It may be possible that these replication factors are
      proteins which are able to transactivate MVM DNA replication and hence are
      accessory replication factors.

PMID- 8151756
TI  - Alternative splicing of pre-mRNAs encoding the nonstructural proteins of minute
      virus of mice is facilitated by sequences within the downstream intron.
AB  - mRNAs R1 and R2 of the parvovirus minute virus of mice encode the two essential
      viral regulatory proteins NS1 and NS2. Both RNAs are spliced between map units 44
      and 46 (nucleotides 2280 and 2399); R2 RNAs are additionally spliced upstream
      between map units 10 and 39 (nucleotides 514 and 1989), using a nonconsensus
      donor and poor 3' splice site. The relative accumulation of R1 and R2 is
      determined by alternative splicing: there is twice the steady-state accumulation
      of R2 relative to that of R1 throughout viral infection, though they are
      generated from the same promoter and have indistinguishable stabilities. Here we
      demonstrate that efficient excision of the large intron to generate R2 is
      dependent on at least the initial presence, in P4-generated pre-mRNAs, of
      sequences within the downstream small intron. This effect is orientation
      dependent and related to the size of the intervening exon. Prior splicing of the
      small intron is unnecessary. Excision of the large intron is enhanced by changing
      its donor site to consensus, but only in the presence of the small intron
      sequences. Excision of the large intron is also enhanced by improving the
      polypyrimidine tract within its 3' splice site; however, in contrast, this change
      renders excision of the large intron independent of the downstream small intron.
      We suggest that sequences within the small intron play a primary role in
      efficient excision of the upstream large intron, perhaps as the initial entry
      site(s) for an element(s) of the splicesome, which stabilizes the binding of
      required factors to the polypyrimidine tract within the 3' splice site of the
      large intron.

PMID- 8151757
TI  - Stabilization of the tumor suppressor p53 during cellular transformation by
      simian virus 40: influence of viral and cellular factors and biological
      consequences.
AB  - To understand the process and biological significance of metabolic stabilization
      of p53 during simian virus 40 (SV40)-induced cellular transformation, we analyzed
      cellular and viral parameters involved in this process. We demonstrate that
      neither large T expression as such nor the cellular phenotype (normal versus
      transformed) markedly influence the stability of p53 complexed to large T in SV40
      abortively infected BALB/c mouse fibroblasts. In contrast, metabolic
      stabilization of p53 is an active cellular event, specifically induced by SV40.
      The ability of SV40 to induce a cellular response leading to stabilization of p53
      complexed to large T is independent from the cellular phenotype and greatly
      varies between different cells. However, metabolic stability was conferred only
      to p53 in complex with large T, whereas the free p53 in these cells remained
      metabolically unstable. Comparative analyses of cellular transformation in
      various cells differing in stability of p53 complexed to large T upon abortive
      infection with SV40 revealed a strong correlation between the ability of SV40 to
      induce metabolic stabilization and its transformation efficiency. Our data
      suggest that metabolic stabilization and the ensuing enhanced levels of p53 are
      important for initiation and/or maintenance of SV40 transformation.

PMID- 8151758
TI  - Expression of hepatitis delta virus RNA deletions: cis and trans requirements for
      self-cleavage, ligation, and RNA packaging.
AB  - The hepatitis delta virus (HDV) genome is a circular, single-stranded, rod
      shaped, 1.7-kb RNA that replicates via a rolling-circle mechanism. Viral
      ribozymes function to cleave replication intermediates which are then ligated to
      generate the circular product. HDV expresses two forms of a single protein, the
      small and large delta antigens (delta Ag-S and delta Ag-L), which associate with
      viral RNA in a ribonucleoprotein (RNP) structure. While delta Ag-S is required
      for RNA replication, delta Ag-L inhibits this process but promotes the assembly
      of the RNP into mature virions. In this study, we have expressed full-length and
      deleted HDV RNA inside cells to determine the minimal RNA sequences required for
      self-cleavage, ligation, RNP packaging, and virion assembly and to assess the
      role of either delta antigen in each of these processes. We report the following
      findings. (i) The cleavage and ligation reactions did not require either delta
      antigen and were not inhibited in their presence. (ii) delta Ag-L, in the absence
      of delta Ag-S, formed an RNP with HDV RNA which could be assembled into secreted
      virus-like particles. (iii) Full-length HDV RNAs were stabilized in the presence
      of either delta antigen and accumulated to much higher levels than in their
      absence. (iv) As few as 348 nucleotides of HDV RNA were competent for circle
      formation, RNP assembly, and incorporation into virus-like particles. (v) An HDV
      RNA incapable of folding into the rod-like structure was not packaged by delta Ag
      L.

PMID- 8151759
TI  - Why is CpG suppressed in the genomes of virtually all small eukaryotic viruses
      but not in those of large eukaryotic viruses?
AB  - Dinucleotide over- and underrepresentation is evaluated in all available
      completely sequenced DNA or RNA viral genomes, ranging in size from 3 to 250 kb
      (available RNA viruses fall into the small-virus category). The dinucleotide CpG
      is statistically underrepresented (suppressed) in all but four of the small
      viruses (more than 75 with lengths of < 30 kb) but has normal relative abundances
      in most large viruses (> or = 30 kb). Most retrotransposons in eukaryotic species
      also show low CpG relative abundances. Interpretations, especially in some cases
      of DNA viruses or viruses with a DNA intermediate, might relate to methylation
      effects and modes of viral integration and excision. Other possible contributing
      factors relate to dinucleotide stacking energies, special mutation mechanisms,
      and evolutionary events.

PMID- 8151760
TI  - Role of the cytoskeleton in cell-to-cell transmission of human immunodeficiency
      virus.
AB  - We previously observed that when human immunodeficiency virus (HIV)-infected T
      lymphocytes are added to epithelial cells, they adhere, polarize, and secrete
      virions unidirectionally onto the epithelium. Epithelial cells subsequently take
      up virus and become productively infected. We report here that colchicine
      treatment of T-lymphocyte suspensions induced lymphocyte polarization,
      redistribution of F-actin into a pseudopod, and secretion of HIV from the
      pseudopod. Immobilization of T lymphocytes on negatively charged plastic also
      caused redistribution of F-actin and unidirectional secretion of HIV onto the
      plastic. As neither colchicine nor adhesion caused an increase in HIV secretion,
      they apparently act by focusing secretion to the tip of the pseudopod. We
      speculate that adhesion-induced polar secretion of HIV, from activated
      mononuclear cells onto epithelia, is a cytoskeleton-mediated process which may be
      involved in HIV transmission in vivo.

PMID- 8151761
TI  - Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an
      intact nef gene.
AB  - The replication competence of human immunodeficiency virus type 1 genomes
      containing mutations in the nef open reading frame was evaluated in continuous
      cell lines. Mutants that contained a deletion in the nef open reading frame,
      premature termination codons, or missense mutations in the N-terminal
      myristoylation signal were constructed. The replication of these mutants was
      tested in three ways. First, plasmid genomes were used to transfect T
      lymphoblastoid cells. Second, low-passage posttransfection supernatants were used
      to infect cells with a relatively low virus input. Third, high-titer virus stocks
      were used to infect cells with a relatively high virus input. These experiments
      demonstrated a 100- to 10,000-fold decrement in p24 production by the nef mutants
      compared with that by the wild-type virus. The greatest difference was obtained
      after infection with the lowest virus input. The myristoylation signal was
      critical for this positive effect of nef. To investigate the mechanism of the
      positive influence of nef, nef-positive and nef-minus viruses were compared
      during a single cycle of replication. These single-cycle experiments were
      initiated both by infection with high-titer virus stocks and by transfection with
      viral DNA. Single-cycle infection yielded a three- to fivefold decrement in p24
      production by nef-minus virus. Single-cycle transfection yielded equal amounts of
      p24 production. These results implied that nef does not affect replication after
      the provirus is established. In support of these results, viral production from
      cells chronically infected with nef-positive or nef-minus viruses was similar
      over time. To determine whether the effect of nef was due to infectivity, end
      point titrations of nef-positive and nef-minus viruses were performed. nef
      positive virus had a greater infectivity per picogram of HIV p24 antigen than nef
      minus virus. These data indicated that the positive influence of nef on viral
      growth rate is due to an infectivity advantage of virus produced with an intact
      nef gene.

PMID- 8151762
TI  - Distribution and trafficking of JHM coronavirus structural proteins and virions
      in primary neurons and the OBL-21 neuronal cell line.
AB  - The neurotropic murine coronavirus JHM is capable of inducing various forms of
      neurologic diseases, including demyelination. Neurons have been shown to act as a
      repository site at the early stages of the disease process (O. Sorensen and S.
      Dales, J. Virol. 56:434-438, 1985). JHM virus (JHMV) replication and trafficking
      of viral proteins and virions in cultured rat hippocampal neurons and a neuronal
      cell line, OBL-21, were examined, with an emphasis placed on the role of the
      microtubular network. We show here that JHMV spread within the central nervous
      system occurs transneuronally and that virus protein trafficking was dependent
      upon microtubules. Viral trafficking occurred asymmetrically, involving both the
      somatodendritic and the axonal domains. Thus coronavirus can be disseminated from
      neurons at either the basolateral or the apical domains. A specific interaction
      between antibodies derived against the microtubule-associated protein tau and
      JHMV nucleocapsid protein (N) was observed, which can presumably be explained by
      an overall amino acid similarity of 44% and an identity of 20% between proteins N
      and tau, with optimal alignment at the microtubule binding domain of tau.
      Collectively, our data suggest an important role of the microtubule network in
      viral protein trafficking and distribution. They also draw attention to protein
      sequence mimicry of a cell component by this coronavirus as one strategy for
      making use of the host's functions on behalf of the virus.

PMID- 8151763
TI  - The UL21 gene products of herpes simplex virus 1 are dispensable for growth in
      cultured cells.
AB  - A viral deletion mutant (delta UL21) that lacked the sequences encoding 484 of
      the predicted first 535 amino acids of the UL21 open reading frame was
      genetically engineered and studied with respect to its phenotype in cells in
      culture. We report the following. (i) The replication of delta UL21 was identical
      to that of the parent herpes simplex virus 1 (HSV-1) strain F in Vero cells, but
      the yields were three- to fivefold lower than those of the parent virus in human
      embryonic lung cells. (ii) To characterize the UL21 protein, we immunized rabbits
      against a purified bacterial fusion protein consisting of glutathione S
      transferase fused to the majority of the coding domain of the UL21 gene. Rabbit
      antiserum directed against the fusion protein recognized a broad band with an
      apparent M(r) of 62,000 to 64,000 in lysates of cells infected with HSV-1 strain
      F and in virions purified from the infected cell cytoplasm. This band was absent
      from lysates of mock-infected cells or cells infected with the delta UL21 virus.
      The band was significantly reduced in intensity in lysates of cells infected in
      the presence of phosphonoacetic acid, indicating that it is expressed as a late
      (gamma 1) gene. (iii) Immunofluorescence studies localized the UL21 antigen
      primarily in brightly staining granules in the cytoplasms of infected cells.
      Taken together, the data indicate that the UL21 protein is a virion component
      dispensable for all aspects of replication of HSV-1 in the cells tested. The
      electrophoretic mobility of the UL21 protein suggests that it is extensively
      modified posttranslationally.

PMID- 8151764
TI  - Human cytomegalovirus maturational proteinase: expression in Escherichia coli,
      purification, and enzymatic characterization by using peptide substrate mimics of
      natural cleavage sites.
AB  - The proteolytic processing of the human cytomegalovirus (HCMV) assembly protein,
      resulting in truncation of its C terminus, is an essential step in virion
      maturation. The proteinase responsible for this cleavage is the amino-terminal
      half of the protein encoded by the UL80a open reading fame. We have obtained high
      expression levels of this 256-amino-acid HCMV proteinase, assemblin, in
      Escherichia coli. In addition to the 28-kDa proteinase, a 15-kDa protein
      comprising the first 143 amino acids and a 13-kDa protein comprising the last 113
      amino acids of the 28-kDa HCMV proteinase were present. Both the 28-kDa
      proteinase and the 15-kDa protein were purified by a two-step chromatographic
      procedure utilizing anion exchange in urea and dithiothreitol and size exclusion
      in NaSCN and dithiothreitol. Activation of the purified 28-kDa proteinase
      required denaturation in urea as well as complete reduction of all five cysteine
      residues in the molecule. Removal of the urea by dialysis with retention of the
      reducing agent yielded an active proteinase. Addition of glycerol to 50% enhanced
      the activity. The HCMV proteinase cleaved the peptides RGVVNASSRLAK and
      SYVKASVSPE, which are mimics of the maturational (M)- and release (R)-site
      sequences, respectively, in the UL80a-encoded protein. The cleavage site in the
      peptides was at the same Ala-Ser scissile bond as observed in the UL80a protein.
      The Km value for the cleavage of RGVVNASSRLAK (M-site mimic) by the proteinase
      was similar to that for SYVKASVSPE (R-site mimic), but the turnover (kcat) of the
      M-site peptide mimic substrate by the proteinase was six to eight times faster.
      The peptide homologs of the herpes simplex virus type 1 M- and R-site sequences
      in the UL26-encoded protein were also cleaved by the HCMV proteinase, although at
      rates slower than those for the HCMV substrates. The HCMV proteinase was
      inhibited by Zn2+ and by alkylating agents, but only at very high inhibitor
      concentrations. The purified 15-kDa protein, subjected to the same activation
      conditions as the 28-kDa proteinase, had no enzymatic activity against the HCMV M
      and R-site peptide substrates.

PMID- 8151766
TI  - Phosphorylation of the duck hepatitis B virus capsid protein associated with
      conformational changes in the C terminus.
AB  - The capsid protein of duck hepatitis B virus (DHBV) is phosphorylated at multiple
      sites during viral infection. A cluster of sites is located near the C terminus
      of the 262-amino-acid protein. We have used site-directed mutagenesis to show
      that three serines and one threonine serve as phosphate acceptor amino acids in
      the C terminus. An additional six potential phosphate acceptor sites in this
      region were apparently not utilized. Each serine or threonine that served as a
      phosphate acceptor was adjacent to a downstream proline, while all six serines
      that were not acceptors for phosphate residues lacked adjacent downstream
      prolines. Mutation of the downstream proline to glycine at each site had the same
      effect as mutating the serine itself, suggesting an SP or TP motif as an
      essential feature for capsid protein phosphorylation. Phosphorylation at these
      four sites resulted in complex shifts in electrophoretic mobility in sodium
      dodecyl sulfate gels of the capsid protein or of a C-terminal peptide containing
      the phosphorylated sites, suggesting that specific conformations of the C
      terminus are associated with different combinations of phosphorylated serines. We
      speculate that distinct functions of the C terminus may be associated with
      different phosphorylated domains on the intact capsid.

PMID- 8151765
TI  - Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for
      their abilities to negatively regulate AAV p5 and p19 mRNA levels.
AB  - The rep gene of adeno-associated virus type 2 (AAV) encodes four overlapping Rep
      proteins that are involved in gene regulation and replication of the virus. We
      studied here the regulation of mRNA transcribed from the AAV p5 and p19
      promoters, using transient expression in human 293 cells followed by Northern
      (RNA) blot analysis of the mRNA. The p5 transcript encodes the larger Rep
      proteins, Rep78 and Rep68, while the p19 transcript encodes the smaller proteins,
      Rep52 and Rep40. A plasmid (pNTC3) containing the entire AAV genome with an amber
      mutation in the rep gene accumulated higher levels of p5 and p19 mRNA than a
      plasmid containing the wild-type AAV genome. Addition of increasing amounts of
      the wild-type rep gene in trans from a heterologous promoter inhibited p5 and p19
      mRNA accumulation from pNTC3, indicating that the levels of both transcripts were
      decreased by the Rep proteins. Cotransfections with plasmids producing individual
      wild-type Rep proteins in trans showed that p5 and p19 mRNA accumulation was
      inhibited 5- to 10-fold by Rep78 and Rep68 and 2- to 3-fold by Rep52 and Rep40.
      Analysis of carboxyl-terminal truncation mutants of Rep78 showed that the ability
      of Rep78 to decrease p5 and p19 mRNA levels was lost when 159 or more amino acids
      were deleted. Rep78 and Rep68 mutants deleted for the methionine at residue 225
      showed decreased abilities to down-regulate both p5 and p19 transcript levels,
      while mutants containing a substitution of glycine for the methionine resembled
      the wild-type Rep78. A Rep78 protein with a mutation in the putative nucleoside
      triphosphate binding site inhibited expression from p5 but not from p19,
      suggesting that the regulation of p5 transcript levels by Rep78 and Rep68 differs
      from that of p19. A deletion analysis of AAV cis sequences revealed that an
      intact terminal repeat was not required for negative regulation of p5 and p19
      transcript levels and that the regulation of p19 mRNA levels by Rep78 did not
      require the presence of the p5 promoter.

PMID- 8151767
TI  - An ATF/CREB site is the major regulatory element in the human herpesvirus 6 DNA
      polymerase promoter.
AB  - Human herpesvirus 6 (HHV-6) is a recently described T-cell pathogen whose medical
      relevance and molecular biology are just beginning to be addressed. As a first
      look at the regulation of viral genes, control of the HHV-6 DNA polymerase
      promoter was examined. Polymerase gene transcription in HHV-6-infected cells was
      found to initiate from a single site located 115 bases upstream of the
      translation start codon. A polymerase promoter-chloramphenicol acetyltransferase
      reporter gene construct failed to be expressed in uninfected T cells but was
      highly active in HHV-6-infected cells. Mutational data indicated that the
      polymerase promoter is TATA-less. Mutational analysis also revealed that the
      major upstream promoter regulatory element required for transcriptional activity
      in HHV-6-infected cells is a palindromic ATF/CREB transcription factor binding
      site. The significance of this site for promoter induction was further
      demonstrated by the fact that the polymerase ATF/CREB element, when appended to a
      heterologous basal promoter, is highly responsive to HHV-6 infection. Two protein
      complexes were found to bind in a specific manner to the ATF/CREB motif in both
      uninfected and HHV-6-infected T-cell nuclear extracts. Site-specific mutation of
      the ATF/CREB site resulted in loss of protein binding as well as loss of promoter
      activity in HHV-6-infected cells.

PMID- 8151768
TI  - Structure and transcription of an immediate-early region in the human herpesvirus
      6 genome.
AB  - The unique segment of the human herpesvirus 6 (HHV-6) genome is essentially
      collinear to the unique long DNA segment of another betaherpesvirus, the human
      cytomegalovirus (HCMV). However, the HHV-6 genomic section that is analogous in
      position to the major immediate-early (IE) locus of HCMV does not exhibit
      recognizable sequence homologies. The respective HHV-6 region of 5.5 kbp is
      flanked on one side by 25 to 28 incomplete tandem repeats of 105 to 110 bp that
      contain, with one exception, a single KpnI restriction site (KpnI repeats). About
      250 reiterations of the sequence motif CACATA are located on the other end. We
      identified two open reading frames of 375 and 2,595 nucleotides, respectively, on
      one strand. Strand-specific Northern blot analyses with RNA harvested from HHV-6
      (strain U1102)-infected HSB-2 cells or cord blood lymphocytes revealed two
      transcripts of about 3.5 and 4.7 kb in the corresponding orientation. Sequence
      analyses of the respective cDNA clones and primer extension experiments were used
      to map the mRNAs. The two transcripts are coterminal and multiply spliced and
      code for the same putative 104.6-kDa protein, but they are initiated from
      different promoters. Characterization of smaller cDNA clones and Northern
      blotting with other strand-specific probes showed that singly spliced mRNAs of
      1.0 and 1.5 kb are transcribed from the opposite strand; they could code for a
      17.2-kDa polypeptide. Blocking experiments with cycloheximide led to the
      conclusion that only the 3.5-kb mRNA is synthesized in the absence of protein
      biosynthesis upon infection with cell-free virus. This identifies a single IE
      gene of HHV-6 at the genomic position corresponding to the major IE region of
      HCMV, although the coding content and transcriptional regulation are quite
      different for these two herpesvirus IE regions.

PMID- 8151769
TI  - Elements distinct from human immunodeficiency virus type 1 splice sites are
      responsible for the Rev dependence of env mRNA.
AB  - In the absence of the viral regulatory protein Rev, the human immunodeficiency
      virus type 1 gag/pol and env mRNAs are inefficiently expressed, since
      nucleocytoplasmic transport, stability, and polysomal loading are impaired. It
      has been suggested that splicing is necessary for Rev function and that the low
      expression of the unspliced and intermediate spliced mRNAs in the absence of Rev
      is associated with specific splice sites. Previous studies identified distinct
      RNA elements within the gag/pol region responsible for low expression that are
      not associated with splice sites. Here we study the determinants for Rev
      dependence of the authentic env mRNA. We demonstrate that upon removal of all the
      utilized splice sites, the env mRNA is still Rev dependent and Rev responsive for
      expression in human cells. We have identified several regions within the env mRNA
      that inhibit expression of a gag-env hybrid mRNA. Elimination of one of these
      elements, located within the Rev-responsive element, did not result in virus
      expression, supporting our model that several independently acting elements are
      responsible for the downregulatory effect. By analogy to the RNA elements within
      the gag/pol region, we propose that elements unrelated to utilized splice sites
      are responsible for the posttranscriptional regulation of env mRNA.

PMID- 8151770
TI  - Structure and heterogeneity of the a sequences of human herpesvirus 6 strain
      variants U1102 and Z29 and identification of human telomeric repeat sequences at
      the genomic termini.
AB  - The unit-length genome of human herpesvirus 6 (HHV-6) consists of a single unique
      component (U) bounded by direct repeats DRL and DRR and forms head-to-tail
      concatemers during productive infection. cis-elements which mediate cleavage and
      packaging of progeny virions (a sequences) are found at the termini of all
      herpesvirus genomes. In HHV-6, DRL and DRR are identical and a sequences may
      therefore also occur at the U-DR junctions to give the arrangement aDRLa-U-aDRRa.
      We have sequenced the genomic termini, the U-DRR junction, and the DRR.DRL
      junction of HHV-6 strain variants U1102 and Z29. A (GGGTTA)n motif identical to
      the human telomeric repeat sequence (TRS) was found adjacent to, but did not
      form, the termini of both strain variants. The DRL terminus and U-DRR junction
      contained sequences closely related to that of the well-conserved herpesvirus
      packaging signal Cn-Gn-Nn-Gn (pac-1), followed by tandem arrays of TRSs separated
      by single copies of a hexanucleotide repeat. HHV-6 strain U1102 contained repeat
      sequences not found in HHV-6 Z29. In contrast, the DRR terminus of both variants
      contained a simple tandem array of TRSs and a close homolog of a herpesvirus pac
      2 signal (GCn-Tn-GCn). The DRR.DRL junction was formed by simple head-to-tail
      linkage of the termini, yielding an intact cleavage signal, pac-2.x.pac-1, where
      x is the putative cleavage site. The left end of DR was the site of intrastrain
      size heterogeneity which mapped to the putative a sequences. These findings
      suggest that TRSs form part of the a sequence of HHV-6 and that the arrangement
      of a sequences in the genome can be represented as aDRLa-U-a-DRRa.

PMID- 8151771
TI  - Cooperativity among herpes simplex virus type 1 immediate-early regulatory
      proteins: ICP4 and ICP27 affect the intracellular localization of ICP0.
AB  - The results of transient expression assays and studies of viral mutants have
      shown that three of the five immediate-early proteins of herpes simplex virus
      type 1 (HSV-1) perform regulatory functions, individually and cooperatively. As
      part of efforts designed to explore the molecular basis for the functional
      cooperativity among ICP0, ICP4, and ICP27 in the regulation of HSV gene
      expression, we have examined the intracellular localization of ICP0 in cells
      infected with ICP4 and ICP27 null mutant viruses by indirect immunofluorescence.
      Although ICP0 was localized predominantly to the nuclei of wild-type virus
      infected cells, it was found exclusively in the nuclei of ICP27 mutant-infected
      cells and in both the cytoplasm and nuclei of ICP4 mutant-infected cells, the
      cytoplasmic component being especially strong. These observations indicate that
      both ICP4 and ICP27 can affect the intracellular localization of ICP0. Transient
      expression assays with plasmids that express wild-type and mutant forms of ICP0,
      ICP4, and ICP27 confirmed that ICP4 promotes and that ICP27 inhibits the nuclear
      localization of ICP0. These results confirm the observations made for mutant
      virus-infected cells and indicate that the localization pattern seen in infected
      cells can be established by these three immediate-early proteins exclusive of
      other viral proteins. The C-terminal half of ICP27 was shown to be required to
      achieve its inhibitory effect on the nuclear localization of ICP0. The region of
      ICP0 responsive to ICP27 was mapped to the C terminus of the molecule between
      amino acid residues 720 and 769. In addition, the concentration of ICP27 was
      shown to have a significant effect on the intracellular localization of ICP0.
      Because the major regulatory activities of ICP0, ICP4, and ICP27 are expressed in
      the nucleus, the ability of these three proteins collectively to determine their
      own localization patterns within cells adds a new dimension to the complex
      process of viral gene regulation in HSV.

PMID- 8151772
TI  - Papillomavirus contains cis-acting sequences that can suppress but not regulate
      origins of DNA replication.
AB  - Bovine papillomavirus (BPV) DNA has been reported to restrict its own replication
      and that of the lytic simian virus 40 (SV40) origin to one initiation event per
      molecule per S phase, which suggests BPV DNA replication as a model for cellular
      chromosome replication. Suppression of the SV40 origin required two cis-acting
      BPV sequences (NCOR-1 and -2) and one trans-acting BPV protein. The results
      presented in this paper confirm the presence of two NCOR sequences in the BPV
      genome that can suppress polyomavirus (PyV) as well as SV40 origin-dependent DNA
      replication as much as 40-fold. However, in contrast to results of previous
      studies on SV40, most of the suppression of the PyV origin was due to NCOR-1, a
      512-bp sequence that functioned independently of distance or orientation with
      respect to the PyV origin and that was not required for BPV DNA replication.
      Moreover, NCOR-1 alone or together with NCOR-2 did not restrict the ability of
      the PyV ori to reinitiate replication within a single S phase and did not require
      any BPV protein to exert suppression. Furthermore, NCOR-1 did not suppress BPV
      origin-dependent DNA replication except in the presence of PyV large tumor
      antigen (T-ag). Since NCOR-1 suppression of PyV origin activity also varied with
      T-ag concentration, suppression of origins by NCOR sequences appeared to require
      papovavirus T-ag. Therefore, it is unlikely that NCOR sequences are involved in
      regulating BPV DNA replication. When these results are taken together with those
      from other laboratories, BPV appears to be a slowly replicating version of
      papovaviruses rather than a model for origins of DNA replication in eukaryotic
      cell chromosomes.

PMID- 8151773
TI  - Primary stage of feline immunodeficiency virus infection: viral dissemination and
      cellular targets.
AB  - The objective of this study was to identify cellular and organ targets of acute
      feline immunodeficiency virus (FIV) infection in vivo. Tissues of FIV-infected
      cats were studied at eight time points during the first 3 months after
      experimental infection. FIV nucleic acids were first detected by in situ
      hybridization 21 days after infection, approximately 1.5 weeks after lymph node
      enlargement was first observed and 3 weeks before the primary acute flu-like
      illness. The majority of FIV-infected cells were present in lymphoid organs,
      though low numbers of infected cells were noted in nonlymphoid organs as well.
      Germinal centers harbored many of the FIV-infected cells within lymphoid tissues.
      The thymic cortex was also a major site of early infection. Combined in situ
      hybridization and immunohistochemistry revealed that T lymphocytes were the
      primary target of early FIV infection in tissues of cats before the onset of
      clinical signs of acute illness. An unidentified population of mononuclear cells
      and a few macrophages were also infected. During the ensuing acute flu-like
      illness, the proportion of FIV-infected macrophages in tissues increased
      dramatically. This early shift in the predominant cellular localization of FIV
      from T lymphocytes to macrophages may be important for establishing viral
      persistence.

PMID- 8151774
TI  - The cytoplasmic domain of CD4 is sufficient for its down-regulation from the cell
      surface by human immunodeficiency virus type 1 Nef.
AB  - Human immunodeficiency virus type 1 Nef down-regulates surface expression of
      murine and human CD4 but not human CD8. We recently reported that the cytoplasmic
      domain of CD4 is required for its down-regulation by Nef. Using a chimeric
      molecule composed of the extracellular and transmembrane domains of human CD8
      fused to the cytoplasmic domain of human CD4, we show here that the cytoplasmic
      domain of CD4 is sufficient for down-regulation by Nef. Since the cytoplasmic
      domain of CD4 is also the site of its association with p56lck, we used a series
      of CD4 mutants to determine whether the regions of the cytoplasmic domain of CD4
      required for down-regulation by Nef are the same as those required for p56lck
      binding. Our results indicate that the portion of the cytoplasmic domain required
      for the down-regulation of CD4 by Nef overlaps with the binding site of p56lck,
      but the cysteine residues which are essential for the association of CD4 with
      p56lck are not required. This observation raised the possibility that Nef
      competes with p56lck for binding to CD4. However, under conditions which are
      considerably milder than those permissive for coimmunoprecipitation of CD4 and
      p56lck, we found no evidence for an association between Nef and CD4. While a
      decrease in total CD4 was observed in lysates of cells expressing Nef, the levels
      of p56lck were not significantly affected. Pulse-chase experiments further
      revealed a decrease in the half-life of CD4 in Nef-expressing cells. These
      results show that the decrease in surface CD4 expression induced by Nef is
      mediated at least in part by a decrease in the half-life of CD4 protein. These
      results also indicate that a large portion of p56lck is free of CD4 in T cells
      expressing Nef, which could have a significant effect on T-cell function.

PMID- 8151775
TI  - Equine infectious anemia virus trans-regulatory protein Rev controls viral mRNA
      stability, accumulation, and alternative splicing.
AB  - The cis- and trans-acting components of the Rev regulatory pathway employed by
      equine infectious anemia virus (EIAV) to regulate and coordinate viral gene
      expression were examined in complementation experiments. Viral protein expression
      and mRNA expression were compared in cells transiently transfected with wild-type
      or mutant proviruses in combination with Rev expression plasmids. Mutation of the
      predicted rev gene abolished Gag protein synthesis, and this defect was
      complemented, in trans, by Rev. Analysis of viral mRNAs from transfected cells
      confirmed that EIAV expresses five major mRNAs: the full-length and singly
      spliced mRNAs contain introns and encode viral structural proteins while the
      three fully spliced mRNAs, encoding nonstructural genes, are generated by
      alternative splicing. Compared to cells transfected with the wild-type provirus,
      the intron-containing mRNAs produced from the rev-minus mutant were present at
      reduced levels in the nuclear RNA fraction and were not detected in the
      cytoplasm. This pattern of viral mRNA synthesis was restored to the wild-type
      pattern by providing Rev in trans. In contrast to the intron-containing mRNAs,
      cytoplasmic accumulation of the multiply spliced class of mRNAs was independent
      of Rev. Closer examination of the multiply spliced class of viral mRNAs by
      reverse transcriptase-PCR analysis revealed a Rev-dependent alternative splicing
      phenomenon. In the absence of Rev, proviruses expressed a four-exon mRNA at high
      levels; the addition of Rev caused both a decrease in the levels of the four-exon
      mRNA and the appearance of a related mRNA lacking exon 3. The cis-acting RNA
      elements that mediate Rev responsiveness were studied with deleted proviruses,
      which revealed that EIAV contains at least two elements located near the ends of
      envelope gene. Unlike the Rev-responsive elements in other retroviruses, the cis
      acting regions of EIAV do not appear to form complex secondary structures.

PMID- 8151776
TI  - Concurrent production of interleukin-2, interleukin-10, and gamma interferon in
      the regional lymph nodes of mice with influenza pneumonia.
AB  - Cytokine production has been assessed at the single-cell level (ELISPOT assay)
      for freshly isolated mediastinal lymph node cells from C57BL/6 mice with primary,
      nonfatal influenza pneumonia. The mediastinal lymph node populations were also
      secondarily stimulated in vitro, and culture supernatants were assayed by enzyme
      linked immunosorbent assay. Both approaches showed minimal evidence of protein
      secretion for interleukin-4 (IL-4), IL-5, and tumor necrosis factor, while IL-2,
      IL-10, and gamma interferon (IFN-gamma) were prominent throughout the response.
      The numbers of IL-2- and IFN-gamma-producing cells were maximal at 7 days after
      infection, while the total counts for cells secreting IL-10 were fairly constant
      from day 3 to 7. The cultures that were stimulated with virus in vitro showed in
      inverse relationship between IL-10 and IFN-gamma production, with IL-10 peaking
      on day 3 and IFN-gamma peaking on day 7. Lymphocytes secreting IL-2, IL-10,
      and/or IFN-gamma were present in CD4+ and CD8+ populations separated by
      fluorescence-activated cell sorting, although the CD8+ T cells produced less
      cytokine and were at a relatively lower frequency. Addition of recombinant IL-10
      to the virus-stimulated cultures decreased the amount of IFN-gamma that could be
      detected, while incorporation of a monoclonal antibody to IL-10 had the opposite
      effect. A neutralization experiment also indicated that IL-2 was the principal
      mediator of lymphocyte proliferation. These experiments thus show that the
      developing T-cell response in the regional lymph nodes of mice with influenza
      cannot be rigidly categorized on the basis of a TH1 or TH2 phenotype and suggest
      possible regulatory mechanisms.

PMID- 8151777
TI  - Reverse genetics provides direct evidence for a correlation of hemagglutinin
      cleavability and virulence of an avian influenza A virus.
AB  - To obtain direct evidence for a relationship between hemagglutinin (HA)
      cleavability and the virulence of avian influenza A viruses, we generated a
      series of HA cleavage mutants from a virulent virus, A/turkey/Ontario/7732/66
      (H5N9), by reverse genetics. A transfectant virus containing the wild-type HA
      with R-R-R-K-K-R at the cleavage site, which was readily cleaved by endogenous
      proteases in chicken embryo fibroblasts (CEF), was highly virulent in
      intramuscularly or intranasally/orally inoculated chickens. By contrast, a mutant
      containing the HA with an avirulent-like sequence (R-E-T-R) at the cleavage site,
      which was not cleaved by the proteases in CEF, was avirulent in chickens,
      indicating that a genetic alteration confined to the HA cleavage site can affect
      cleavability and virulence. Mutant viruses with HA cleavage site sequences of T-R
      R-K-K-R or T-T-R-K-K-R were as virulent as viruses with the wild-type HA, whereas
      a mutant with a two-amino-acid deletion but retention of four consecutive basic
      residues (R-K-K-R) was as avirulent as a virus with the avirulent-type HA.
      Interestingly, although a mutant containing an HA with R-R-R-K-T-R, which has
      reduced cleavability in CEF, was as virulent as viruses with high HA cleavability
      when given intramuscularly, it was less virulent when given intranasally/orally.
      We conclude that the degree of HA cleavability in CEF predicts the virulence of
      avian influenza viruses.

PMID- 8151778
TI  - Extensive envelope heterogeneity of simian immunodeficiency virus in tissues from
      infected macaques.
AB  - The extent of virus genetic variation within tissues and peripheral blood
      mononuclear cells (PBMC) from two simian immunodeficiency virus (SIV)-infected
      macaques was analyzed. The products of PCR amplification of two regions, region 1
      (SIV V1 region) and region 2 (region corresponding to the human immunodeficiency
      virus V3 cysteine loop and part of the C3 region immediately downstream), of the
      SIV envelope were examined for single-stranded conformation polymorphism followed
      by sequence analysis of selected clones. The V1 region of the SIV envelope of
      viruses present within lymphoid tissues displayed extensive heterogeneity, while
      viral populations within the PBMC and brain appeared to be less variable. Region
      2 heterogeneity in both animals was generally confined to three residues in a
      tissue-specific manner. In addition, virus from the brains of both animals
      appeared to be distinct compared with viruses present in other tissues and PBMC
      of the same animal, both in the pattern of PCR-single-stranded conformation
      polymorphism SCP and in the sequence of region 2. These studies revealed that the
      tissues of SIV-infected macaques were a reservoir for viral variants distinct
      from those seen in PBMC.

PMID- 8151779
TI  - Simian virus 40 small-t antigen stimulates viral DNA replication in permissive
      monkey cells.
AB  - The simian virus 40 (SV40) large-T antigen is essential for SV40 DNA replication
      and for late viral gene expression, but the role of the SV40 small-t antigen in
      these processes is still unclear. We have previously demonstrated that small t
      inhibits SV40 DNA replication in vitro. In this study, we investigated the effect
      of small t on SV40 replication in cultured cells. CV1 monkey cell infection
      experiments indicated that mutant viruses that lack small t replicate less
      efficiently than the wild-type virus. We next microinjected CV1 cells with SV40
      DNA with and without purified small-t protein and analyzed viral DNA replication
      efficiency by Southern blotting. Replication of either wild-type SV40 or small-t
      deletion mutant DNA was increased three- to fivefold in cells coinjected with
      purified small t. Thus, in contrast to our in vitro observation, small t
      stimulated viral DNA replication in vivo. This result suggests that small t has
      cellular effects that are not detectable in a reconstituted in vitro replication
      system. We also found that small t stimulated progression of permissive monkey
      cells--but not of nonpermissive rodent cells--from G0-G1 to the S phase of the
      cell cycle, possibly leading to an optimal intracellular environment for viral
      replication.

PMID- 8151780
TI  - Identification and zinc dependence of the bovine herpesvirus 1 transactivator
      protein BICP0.
AB  - Bovine herpesvirus 1 (BHV-1) specifies and unspliced early 2.6-kb RNA (ER2.6)
      which is 3' coterminal with exon 2 of the 2.9-kb immediate-early (IE) RNA. The
      two transcripts have a common open reading frame (676 codons). The predicted
      protein, designated BHV-1 infected cell protein 0 (BICP0), contains a zinc finger
      domain with homology to ICP0 of herpes simplex virus type 1 and protein 61 of
      varicella-zoster virus, and depending on the promoter, it acts as a strong
      activator or as a repressor in transient expression assays. In situ
      immunoadsorbent assays using antisera against synthetic oligopeptides
      demonstrated that BICP0 accumulates in nuclei of BHV-1-infected cells, as
      expected for an IE gene product involved in gene regulation. Western blots
      (immunoblots) revealed a BHV-1-specific 97-kDa protein which was detectable
      during the IE phase and also at later periods of infection, indicating that the
      kinetics of BICP0 synthesis is consistent with the switch from IER2.9 to ER2.6.
      To confirm that ER2.6 encoded the 97-kDa BICP0 protein, a DNA fragment containing
      BICP0-coding sequences was inserted into the Autographa californica baculovirus
      genome. A recombinant protein, identified by its reactivity with antipeptide
      sera, exhibited the same electrophoretic mobility as BICP0 specified by BHV-1. We
      microinjected Xenopus oocytes with a BICP0 effector plasmid and a promoter
      chloramphenicol acetyltransferase plasmid. BICP0-induced stimulation of this
      promoter was strongly reduced when intracellular zinc was chelated by thionein,
      indicating that the effect of BICP0 is zinc dependent.

PMID- 8151781
TI  - Encephalomyocarditis virus internal ribosomal entry site RNA-protein
      interactions.
AB  - Translational initiation of encephalomyocarditis virus (EMCV) mRNA occurs by
      ribosomal entry into the 5' nontranslated region of the EMCV mRNA, rather than by
      ribosomal scanning. Internal ribosomal binding requires a cis-acting element
      termed the internal ribosomal entry site (IRES). IRES elements have been proposed
      to be involved in the translation of picornavirus mRNAs and some cellular mRNAs.
      Internal ribosome binding likely requires the interaction of trans-acting factors
      that recognize both the mRNA and the ribosomal complex. Five cellular proteins
      (p52, p57, p70, p72, and p100) cross-link the EMCV IRES or fragments of the IRES.
      For one of these proteins, p57, binding to the IRES correlates with translation.
      Recently, p57 was identified to be very similar, if not identical, to
      polypyrimidine tract-binding protein. On the basis of cross-linking results with
      21 different EMCV IRES fragments and cytoplasmic HeLa extract or rabbit
      reticulocyte lysate as the source of polypeptides, consensus binding sites for
      p52, p57, p70, and p100 are proposed. It is suggested that each of these proteins
      recognizes primarily a structural feature of the RNA rather than a specific
      sequence.

PMID- 8151782
TI  - Hepatitis B virus RNA element that facilitates accumulation of surface gene
      transcripts in the cytoplasm.
AB  - Hepatitis B virus enhancers I and II are critical for high-level expression from
      the viral major surface gene promoter. These enhancers are in an unusual
      position, since both are entirely contained within the downstream transcribed
      region of the surface gene. In this report, we present data showing that a
      fragment of the viral genome encompassing enhancer II activates accumulation of
      surface gene transcripts at the posttranscriptional level. Specifically, the
      total steady-state amount of surface gene transcripts in the cell drops by more
      than fourfold when enhancer II is displaced to a position downstream of the
      transcription termination site. There is a similar decrease in the amount of
      cytoplasmic surface gene transcripts but not of nuclear transcripts. These
      changes in steady-state transcript levels do not result from a decrease in the
      rate of transcriptional initiation or from an increased rate of degradation in
      the cytoplasm. Reinsertion of enhancer II in the correct orientation into the
      surface gene transcribed region partially restores transcript levels. From these
      data, we conclude that a hepatitis B virus RNA element functions in cis to
      increase the steady-state levels of surface gene transcripts by facilitating
      cytoplasmic accumulation of these transcripts.

PMID- 8151783
TI  - Assignment of disulfide bridges in the fusion glycoprotein of Sendai virus.
AB  - The mature fusion (F) glycoprotein of the paramyxovirus family consists of two
      disulfide-linked subunits, the N-terminal F2 and the C-terminal F1 subunits, and
      contains 10 cysteine residues which are highly conserved at specific positions.
      The high level of conservation strongly suggests that they are indeed disulfide
      linked and play important roles in the folding and functioning of the molecule.
      However, it has not even been clarified which cysteine residues link the F2 and
      F1 subunits. This report describes our assignment of the disulfide bridges in
      purified Sendai virus F glycoprotein by fragmentation of the polypeptide and
      isolation of cystine-containing peptides and determination of their N-terminal
      sequences. The data demonstrate that all of the 10 cysteine residues participate
      in disulfide bridges and that Cys-70, the only cysteine in F2, and Cys-199, the
      most upstream cysteine in F1, form the interchain bond. Of the remaining eight
      cysteine residues clustered near the transmembrane domain of F1, the specific
      bridges identified are Cys-338 to Cys-347 and Cys-362 to Cys-370. Although no
      exact pairings between the subsequent four residues were defined, it seems likely
      that the most downstream, Cys-424, is linked to Cys-394, Cys-399, or Cys-401.
      Thus, we conclude that the cysteine-rich domain indeed contributes to the
      formation of a bunched structure containing at least two tandem cystine loops.

PMID- 8151785
TI  - Identification of human immunodeficiency virus type 1 Gag protein domains
      essential to membrane binding and particle assembly.
AB  - Assembly of human immunodeficiency virus type 1 (HIV-1) particles occurs at the
      plasma membrane of infected cells. Myristylation of HIV-1 Gag precursor
      polyprotein Pr55Gag is required for stable membrane binding and for assembly of
      viral particles. We expressed a series of proteins representing major regions of
      the HIV-1 Gag protein both with and without an intact myristyl acceptor glycine
      and performed subcellular fractionation studies to identify additional regions
      critical for membrane binding. Myristylation-dependent binding of Pr55Gag was
      demonstrated by using the vaccinia virus/T7 hybrid system for protein expression.
      Domains within the matrix protein (MA) region downstream of the initial 15 amino
      acids were required for membrane binding which was resistant to a high salt
      concentration (1 M NaCl). A myristylated construct lacking most of the matrix
      protein did not associate with the plasma membrane but formed intracellular
      retrovirus-like particles. A nonmyristylated construct lacking most of the MA
      region also was demonstrated by electron microscopy to form intracellular
      particles. Retrovirus-like extracellular particles were produced with a Gag
      protein construct lacking all of p6 and most of the nucleocapsid region. These
      studies suggest that a domain within the MA region downstream from the
      myristylation site is required for transport of Gag polyprotein to the plasma
      membrane and that stable plasma membrane binding requires both myristic acid and
      a downstream MA domain. The carboxyl-terminal p6 region and most of the
      nucleocapsid region are not required for retrovirus-like particle formation.

PMID- 8151784
TI  - pH-independent murine leukemia virus ecotropic envelope-mediated cell fusion:
      implications for the role of the R peptide and p12E TM in viral entry.
AB  - Murine leukemia virus ecotropic and amphotropic envelope expression vectors were
      genetically engineered to generate truncations of the p15E TM cytoplasmic tail.
      The ecotropic construct CEET has the entire cytoplasmic tail of TM deleted, while
      the CEETR construct has only the R peptide portion of the tail deleted, thereby
      producing a TM subunit (p12E) that is identical to the one found in mature
      virions. The analogous amphotropic constructs were called CAET and CAETR. These
      envelopes, as opposed to their p15E TM counterparts, mediate cell-to-cell fusion
      at neutral pH in both transformed and nontransformed cell lines. Though the TM
      cytoplasmic domain is not required, its presence appears to augment such cell-to
      cell fusion. This envelope-dependent fusion requires the presence of the viral
      receptor on the cell surface. Ecotropic virions bearing the p12E TM contain wild
      type levels of the envelope complex and have near-normal titers. In contrast,
      virions which lack the cytoplasmic domain of TM (e.g., CEET) have 10- to 100-fold
      lower titers but contain normal amounts of envelope. Both of the corresponding
      amphotropic virions contain normal amounts of envelope but have 10- to 100-fold
      lower titers. Using immunofluorescent detection of envelope to monitor the fate
      of receptor-bound virions, we found that ecotropic murine leukemia virus envelope
      disappears from the cell surface while amphotropic envelope persists on the cell
      surface after virus binding. This pattern of immunofluorescence is consistent
      with the proposed routes of cell entry for these viruses, i.e., by endocytosis
      and direct fusion, respectively. In this assay, ecotropic virions bearing the
      genetically engineered p12E TM also appear to be internalized despite the ability
      of their envelope to mediate fusion at neutral pH in the same target cells. Our
      results show that direct fusion at neutral pH is a natural consequence of the
      surface expression of the mature ecotropic envelope and its receptor. We propose
      that the processing of the R peptide from the envelope TM (p15E) to yield p12E,
      at the time of virus budding or within virions, renders the envelope competent to
      fuse.

PMID- 8151786
TI  - Human immunodeficiency virus type 1 Nef protein down-regulates transcription
      factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor
      stimulation.
AB  - Human immunodeficiency virus type 1 (HIV-1) negative factor (Nef) has been shown
      to down-regulate the transcription factors NF-kappa B and AP-1 in vitro. To
      define the mechanism of action of the Nef protein, the signal transduction
      pathways which may be affected in T cells by constitutive expression of the nef
      gene were examined. Stimulation of T cells with tumor necrosis factor,
      interleukin-1, or lipopolysaccharide resulted in the recruitment of
      transcriptional factors to a similar level whether or not the cells expressed the
      nef gene. On the other hand, stimulation of T cells by mitogens or antibodies to
      the T-cell receptor (TCR)-CD3 complex resulted in the down-regulation of
      transcriptional factors NF-kappa B and AP-1 in cells expressing the nef gene
      compared with cells not expressing the nef gene. Because the Nef protein does not
      affect the surface expression of the CD3-TCR complex, we conclude that the Nef
      protein down-regulates the transcriptional factors NF-kappa B and AP-1 in T cells
      in vitro through an effect on the TCR-dependent signal transduction pathway.

PMID- 8151789
TI  - Pathogenesis of mucosal disease: a cytopathogenic pestivirus generated by an
      internal deletion.
AB  - Cytopathogenic bovine viral diarrhea virus (BVDV) arises by RNA recombination in
      animals persistently infected with noncytopathogenic BVDV. Such animals develop
      fatal mucosal disease. In this report, the genome of a cytopathogenic BVDV
      isolate, termed CP9, is characterized. CP9-infected cells contained not only
      viral genomic RNA of 12.3 kb but also a BVDV-specific RNA of 8 kb. cDNA cloning
      and sequencing revealed that the 8-kb RNA is a BVDV genome with an internal
      deletion of 4.3 kb. The 8-kb RNA represents the genome of a typical defective
      interfering particle (DI), since its replication was strictly dependent on the
      presence of a helper virus and strongly interfered with the replication of the
      helper. Cell culture experiments demonstrated that the CP9 virus stock contains
      two viruses, namely, a helper virus and DI9. While the helper virus alone was
      noncytopathogenic, the presence of the DI conferred cytopathogenicity. Expression
      experiments demonstrated that p80, the marker protein of cytopathogenic BVDV, is
      translated from the defective genome. The occurrence of this cytopathogenic DI is
      linked to a fatal disease in cattle.

PMID- 8151787
TI  - Mapping of intracellular localization domains and evidence for colocalization
      interactions between the IE110 and IE175 nuclear transactivator proteins of
      herpes simplex virus.
AB  - Transcriptional regulation by the IE175 (ICP4) and IE110 (ICP0) phosphorylated
      nuclear proteins encoded by herpes simplex virus (HSV) appears to be a key
      determinant for the establishment of successful lytic cycle infection. By
      indirect immunofluorescence in transient DNA transfection assays, we have
      examined the intracellular distribution of deletion and truncation mutants of
      both IE175 and IE110 from HSV-1. Insertion of short oligonucleotides encoding the
      basic amino acid motifs 726-GRKRKSP-732 from IE175 and 500-VRPRKRR-506 from IE110
      into deleted cytoplasmic forms of the two proteins restored the karyophilic
      phenotype and confirmed that these motifs are both necessary and sufficient for
      proper nuclear localization. Analysis of IE110 deletion mutants and a panel of
      IE110/IE175 hybrid proteins was also used to evaluate the characteristic IE110
      distribution within nuclear punctate granules as seen by immunofluorescence and
      phase-contrast microscopy. The phase-dense punctate pattern persisted with both
      large C-terminal truncations and deletions of the Cys-rich zinc finger region and
      even with a form of IE110 that localized in the cytoplasm, implying that the
      punctate characteristic is an intrinsic property of the N-terminal segment of the
      IE110 protein. Transfer of the full IE110-like punctate phenotype to the normally
      uniform diffuse nuclear pattern of the IE175 protein by exchange of the N
      terminal domains of the two proteins demonstrated that the first 105 to 244 amino
      acids of IE110 represent the most important region for conferring punctate
      characteristics. Surprisingly, cotransfection of a wild-type nuclear IE175 gene
      together with the IE110 gene revealed that much of the IE175 protein produced was
      redistributed into a punctate pattern that colocalized with the IE110-associated
      punctate granules seen in the same cells. This colocalization did not occur after
      cotransfection of IE110 with the IE72 (IE1) nuclear protein of human
      cytomegalovirus and therefore cannot represent simple nonspecific trapping.
      Evidently, the punctate phenotype of IE110 represents a dominant characteristic
      that reveals the potential of IE110 and IE175 to physically interact with each
      other either directly or indirectly within the intracellular environment.

PMID- 8151790
TI  - Second-site long terminal repeat (LTR) revertants of replication-defective human
      immunodeficiency virus: effects of revertant TATA box motifs on virus
      infectivity, LTR-directed expression, in vitro RNA synthesis, and binding of
      basal transcription factors TFIID and TFIIA.
AB  - Second-site revertants from replication-incompetent molecular clones of human
      immunodeficiency virus (HIV) contain base substitutions adjacent to the TATA
      motif. The altered TATA box motifs were analyzed for their effect(s) on virus
      infectivity, long terminal repeat (LTR)-directed expression in transient
      transfection assays, in vitro RNA synthesis, and assembly of the TFIID-TFIIA
      preinitiation complex. The revertant TATA boxes accelerated the kinetics of HIV
      replication when present in the context of an LTR containing a Sp1 mutation
      (deletion or site specific); no effect was observed on the infectivity of wild
      type HIV. In chloramphenicol acetyltransferase assays and in vitro transcription
      systems, the altered TATA box motifs led to elevated basal levels of RNA
      synthesis from NF-kappa B- and Sp1-mutagenized and wild-type templates,
      respectively, but did not increase responsiveness to Tat transactivation. The
      revertant TATA boxes accelerated the binding of TFIID and TFIIA to the LTR and
      stabilized their association with the promoter. The revertants did not assemble a
      more-processive elongation complex. These results suggest that in the context of
      an impaired enhancer/promoter (viz., three mutated Sp1 elements), a series of HIV
      revertants emerge which contain LTR alterations that significantly augment basal
      RNA synthesis. The TATA motif revertants are capable of rescuing the
      enhancer/promoter defect and sustain virus infectivity.

PMID- 8151788
TI  - Identification of a dimerization domain in the C-terminal segment of the IE110
      transactivator protein from herpes simplex virus.
AB  - The 775-amino-acid IE110 (or ICP0) phosphoprotein of herpes simplex virus (HSV)
      functions as an accessory transcription factor during the lytic cycle and plays a
      critical role in reactivation from latent infection. By immunofluorescence
      analysis, IE110 localizes in a novel pattern consisting of several dozen
      spherical punctate granules in the nuclei of DNA-transfected cells. We
      constructed a hybrid version of IE110 that contained an epitope-tagged domain
      from the N terminus of the HSV IE175 protein and lacked the IE110 N-terminal
      domain that confers punctate characteristics. This hybrid IE175(N)/IE110(C)
      protein gave an irregular nuclear diffuse pattern on its own but was
      redistributed very efficiently into spherical punctate granules after
      cotransfection with the wild-type HSV-1 IE110 protein. Similar colocalization
      interactions occurred with internally deleted forms of IE110 that lacked the zinc
      finger region or large segments from the center of the protein, including both
      cytoplasmic and elongated punctate forms, but C-terminal truncated versions of
      IE110 did not interact. In all such interactions, the punctate phenotype was
      dominant. Evidence that C-terminal segments of IE110 could also form stable mixed
      subunit oligomers in vitro was obtained by coimmunoprecipitation of in vitro
      translated IE110 polypeptides with different-size hemagglutinin epitope-tagged
      forms of the protein. This occurred only when the two forms were cotranslated,
      not when they were simply mixed together. An in vitro-synthesized IE110 C
      terminal polypeptide also gave immunoprecipitable homodimers and heterodimers
      when two different-size forms were cross-linked with glutaraldehyde and reacted
      specifically with a bacterial glutathione S-transferase/IE110 C-terminal protein
      in far-Western blotting experiments. The use of various N-terminal and C-terminal
      truncated forms of IE110 in the in vivo assays revealed that the outer boundaries
      of the interaction domain mapped between codons 617 and 711, although inclusion
      of adjacent codons on either side increased the efficiency severalfold in some
      assays. We conclude that the C-terminal region of IE110 contains a high-affinity
      self-interaction domain that leads to stable dimer and higher-order complex
      formation both in DNA-transfected cells and in in vitro assays. This segment of
      IE110 is highly conserved between HSV-1 and HSV-2 and appears to have the
      potential to play an important role in the interaction with the IE175 protein, as
      well as in correct intracellular localization, but it is not present in the
      equivalent proteins from varicella-zoster virus, pseudorabies virus, or equine
      abortion virus.

PMID- 8151792
TI  - Deletion of the varicella-zoster virus large subunit of ribonucleotide reductase
      impairs growth of virus in vitro.
AB  - Cells infected with varicella-zoster virus (VZV) express a viral ribonucleotide
      reductase which is distinct from that present in uninfected cells. VZV open
      reading frames 18 and 19 (ORF18 and ORF19) are homologous to the herpes simplex
      virus type 1 genes encoding the small and large subunits of ribonucleotide
      reductase, respectively. We generated recombinant VZV by transfecting cultured
      cells with four overlapping cosmid DNAs. To construct a virus lacking
      ribonucleotide reductase, we deleted 97% of VZV ORF19 from one of the cosmids.
      Transfection of this cosmid with the other parental cosmids yielded a VZV mutant
      with a 2.3-kbp deletion confirmed by Southern blot analysis. Virus-specific
      ribonucleotide reductase activity was not detected in cells infected with VZV
      lacking ORF19. Infection of melanoma cells with ORF19-deleted VZV resulted in
      plaques smaller than those produced by infection with the parental VZV. The
      mutant virus also exhibited a growth rate slightly slower than that of the
      parental virus. Chemical inhibition of the VZV ribonucleotide reductase has been
      shown to potentiate the anti-VZV activity of acyclovir. Similarly, the
      concentration of acyclovir required to inhibit plaque formation by 50% was
      threefold lower for the VZV ribonucleotide reductase deletion mutants than for
      parental virus. We conclude that the VZV ribonucleotide reductase large subunit
      is not essential for virus infection in vitro; however, deletion of the gene
      impairs the growth of VZV in cell culture and renders the virus more susceptible
      to inhibition by acyclovir.

PMID- 8151794
TI  - Further characterization of the interaction between the Epstein-Barr virus DNA
      polymerase catalytic subunit and its accessory subunit with regard to the 3'-to
      5' exonucleolytic activity and stability of initiation complex at primer
      terminus.
AB  - The Epstein-Barr virus (EBV) DNA polymerase catalytic subunit, BALF5 gene
      product, possesses an intrinsic 3'-to 5' proofreading exonuclease activity in
      addition to 5'-to-3' DNA polymerase activity (T. Tsurumi, A. Kobayashi, K. Tamai,
      T. Daikoku, R. Kurachi, and Y. Nishiyama, J. Virol. 67:4651-4658, 1993). The
      exonuclease hydrolyzed both double-and single-stranded DNA substrates with 3'-to
      5' directionality, releasing deoxyribonucleoside 5'-monophosphates. The double
      strand exonucleolytic activity catalyzed by the BALF5 polymerase catalytic
      subunit was very sensitive to high ionic strength, whereas the single-strand
      exonucleolytic activity was moderately resistant. The addition of the BMRF1
      polymerase accessory subunit to the reaction enhanced the double-strand
      exonucleolytic activity in the presence of high concentrations of ammonium
      sulfate (fourfold stimulation at 75 mM ammonium sulfate). Optimal stimulation was
      obtained when the molar ratio of BMRF1 protein to BALF5 protein was 2 and higher,
      identical to the values required for reconstituting the optimum DNA polymerizing
      activity (T. Tsurumi, T. Daikoku, R. Kurachi, and Y. Nishiyama, J. Virol. 67:7648
      7653, 1993). Furthermore, product size analyses revealed that the polymerase
      catalytic subunit alone excised a few nucleotides from the 3' termini of the
      primer hybridized to template DNA and that the addition of the BMFR1 polymerase
      accessory subunit stimulated the nucleotide excision several times. In contrast,
      the hydrolysis of single-stranded DNA by the BALF5 protein was not affected by
      the addition of the BMRF1 polymerase accessory subunit at all. These observations
      suggest that the BMRF1 polymerase accessory subunit forms a complex with the
      BALF5 polymerase catalytic subunit to stabilize the interaction of the holoenzyme
      complex with the 3'-OH end of the primer on the template DNA during
      exonucleolysis. On the other hand, challenger DNA experiments revealed that the
      BALF5 polymerase catalytic subunit alone stably binds to the primer terminus in a
      stationary state, whereas the reconstituted polymerase holoenzyme is unstable.
      The instability of the initiation complex of the EBV DNA polymerase would allow
      the rapid removal of the EBV DNA polymerase holoenzyme from the lagging strand
      after it has replicated up to the previous Okazaki fragment. This feature of the
      EBV DNA polymerase holoenzyme in a stationary state is in marked contrast to the
      moving holoenzyme complex tightly bound to the primer end during polymerization
      and exonucleolysis.

PMID- 8151791
TI  - Identification of a region of a murine leukemia virus long terminal repeat with
      novel transcriptional regulatory activities.
AB  - The 93-bp region downstream of the enhancer (DEN) in the long terminal repeat
      (LTR) of the mink cell focus-forming virus (MCF13) has been shown to be important
      for transcriptional activation and viral lymphomagenicity (J. C. Tupper, H. Chen,
      E. F. Hays, G. C. Bristol, and F. K. Yoshimura, J. Virol. 66:7080-7088, 1992). In
      this report, we have further explored the role of the DEN region in
      transcriptional activation. We observed that it has enhancer-like abilities as
      well as some unique LTR properties. Transcriptional activation by the DEN region
      involved interactions with enhancer sequences that were either synergistic or
      additive, depending on the cell type. The most intriguing property of the DEN
      region is its ability to induce transcription in activated T cells. This activity
      is unique for the LTR in that no other LTR region can do this. We also examined
      the role of the DEN region in retroviral lymphomagenesis. We cloned and sequenced
      proviral LTRs integrated upstream of the cellular c-myc gene from DNA obtained
      from thymic tumors induced by DEN region deletion mutant viruses in AKR mice. We
      determined that for transcriptional activation of the c-myc proto-oncogene,
      enhancer sequences can substitute for the DEN region. This study identifies the
      significance of non-enhancer sequences in the LTR for the oncogenesis of the
      MCF13 retrovirus.

PMID- 8151793
TI  - Effects of the Tat basic domain on human immunodeficiency virus type 1
      transactivation, using chemically synthesized Tat protein and Tat peptides.
AB  - To study the structure relationship of different Tat domains, the full-length Tat
      protein Tat1-86, the gene product of the first exon Tat1-72 which retains full
      activity of the protein, and a panel of shorter peptides mimicking different
      regions of the primary structure of the Tat protein were chemically synthesized
      by the solid-phase method, using an efficient protocol. Synthetic Tat1-86 and
      Tat1-72 transactivated beta-galactosidase activity in HeLa cells containing the
      lacZ gene under the control of the human immunodeficiency virus type 1 long
      terminal repeat. Analyses of the activity of Tat1-86 and Tat1-72 with the
      sulfhydryl of cysteine residues free or protected by the acetamidomethyl group
      showed that only the Tat fragments with deprotected cysteine residues retain
      transactivation ability. In contrast, peptide Tat1-48 was inactive, with cysteine
      residues either free or protected. Similarly, other shorter synthetic peptides
      covering the different Tat domains were inactive. Interestingly, when peptides
      Tat1-48 and Tat38-60 were used simultaneously, a significant transactivation was
      obtained. This result suggests that both peptide domains are implicated in
      transactivation, probably by acting at two different sites. This permits us to
      propose a fundamentally new step in the understanding of the molecular mechanism
      of Tat transactivation.

PMID- 8151796
TI  - The human T-cell leukemia virus type I Tax protein induces apoptosis which is
      blocked by the Bcl-2 protein.
AB  - The Tax protein of human T-cell leukemia virus type I activates transcription of
      cellular and viral genes and can immortalize primary T lymphocytes. We have
      previously reported that the Tax protein transforms Rat-1 cells. Here we show
      that Tax-transformed Rat-1 cells detach from plates to undergo apoptotic cell
      death by serum deprivation. These cells exhibit DNA fragmentation into
      oligonucleosomal fragments and chromatin condensation. Constitutive expression of
      a proto-oncogene, bcl-2, effectively blocks Tax-mediated apoptosis caused by
      serum deprivation without affecting the levels of Tax expression and the
      transformed phenotype of the cells.

PMID- 8151795
TI  - A protease activation mutant, MVCES1, as a safe and potent live vaccine derived
      from currently prevailing Sendai virus.
AB  - Sendai virus fresh isolates were shown to be antigenically different from the
      prototype Fushimi strain that had long been passaged in embryonated chicken eggs.
      Phylogenetic analysis of the hemagglutinin-neuraminidase genes also revealed the
      difference between these two virus groups. Both trypsin-resistant and elastase
      sensitive mutations were additionally introduced to an LLC-MK2-cell-adapted and
      attenuated mutant derived from one of the fresh isolates. This protease
      activation mutant (MVCES1) showed the same antigenicity as the fresh isolates,
      and as a result of a single cycle of growth in lungs, it could confer better
      protection on mice against challenge infection with the currently prevailing
      Sendai virus than TR-5, which is a trypsin-resistant mutant derived from the
      Fushimi strain. The eligibility of MVCES1 as an attenuated live vaccine of Sendai
      virus is discussed.

PMID- 8151797
TI  - Feline immunodeficiency virus can be experimentally transmitted via milk during
      acute maternal infection.
AB  - Postnatal transmission of feline immunodeficiency virus (FIV) in neonates nursed
      by acutely infected mothers and infection resulting from oral inoculation of
      kittens with FIV were evaluated. Ten of 16 kittens nursed by four queens with FIV
      infection established immediately postpartum developed FIV infection. Five of 11
      neonates orally administered cell-free FIV culture supernatant developed FIV
      infection. Kittens that developed FIV infection had greater proportions of CD4+
      and Pan-T+ lymphocytes at birth than negative kittens. Infectious virus was
      recovered from the milk of acutely infected mothers. We conclude that FIV may be
      experimentally transmitted via milk from queens with acute infections and that
      oral administration of FIV to neonatal kittens results in infection.

PMID- 8151799
TI  - Identification of minireovirus as a Norwalk-like virus in pediatric patients with
      gastroenteritis.
AB  - In 1977, 30- to 32-nm virus-like particles, named minireovirus because of their
      unique morphologic appearance, were detected by electron microscopy in the stools
      of infants and young children with gastroenteritis. Sequence analysis of
      approximately 2,800 consecutive bases derived from overlapping PCR clones of a
      recent minireovirus clinical isolate showed 52% nucleotide sequence identity with
      the Norwalk virus sequence and, in addition, demonstrated that the genomic
      organizations of these two viruses were similar. Our data show that minireovirus
      is a Norwalk-like virus and should now also be included in the Caliciviridae
      family.

PMID- 8151798
TI  - Purification of recombinant budgerigar fledgling disease virus VP1 capsid protein
      and its ability for in vitro capsid assembly.
AB  - A recombinant system for the major capsid VP1 protein of budgerigar fledgling
      disease virus has been established. The VP1 gene was inserted into a truncated
      form of the pFlag-1 vector and expressed in Escherichia coli. The budgerigar
      fledgling disease virus VP1 protein was purified to near homogeneity by
      immunoaffinity chromatography. Fractions containing highly purified VP1 were
      pooled and found to constitute 3.3% of the original E. coli-expressed VP1
      protein. Electron microscopy revealed that the VP1 protein was isolated as
      pentameric capsomeres. Electron microscopy also revealed that capsid-like
      particles were formed in vitro from purified VP1 capsomeres with the addition of
      Ca2+ ions and the removal of chelating and reducing agents.

PMID- 8151800
TI  - Discrepancy between infectivity and antigenicity stabilization of oral poliovirus
      vaccine by a capsid-binding compound.
AB  - Two hundred forty pyridazinamine derivatives were tested for the ability to
      stabilize the antigenicity and infectivity of oral poliovirus vaccine subjected
      to 45 degrees C for 2 h. Seven compounds stabilized the antigenicity of all three
      vaccine strains and neutralized the viral particles in a way that is reversible
      by dilution. Of these, R 77975 (pirodavir) was selected for vaccine potency
      tests. Sabin type 2 and type 3 strains were subjected to 4, 25, 42, and 45
      degrees C for 1 week in the presence and absence of R 77975. Although R 77975
      particularly stabilized the infectivity of the most thermolabile vaccine strain
      (Sabin type 3), the protection did not exceed that of 1 M MgCl2. When virus was
      inactivated in the absence of R 77975, the native or N antigenicity changed in H
      antigenicity. However, in the presence of the capsid-binding compound, N
      antigenicity was preserved in particles that had lost infectivity.

PMID- 8151802
TI  - Stabilization of short telomeres and telomerase activity accompany
      immortalization of Epstein-Barr virus-transformed human B lymphocytes.
AB  - We have measured telomere length and telomerase activity throughout the life span
      of clones of human B lymphocytes transformed by Epstein-Barr virus. Shortening of
      telomeres occurred at similar rates in all populations and persisted until
      chromosomes had little telomeric DNA remaining. At this stage, some of the clones
      entered a proliferative crisis and died. Only clones in which telomeres were
      stabilized, apparently by activation of telomerase, continued to proliferate
      indefinitely, i.e., became immortal. Since loss of telomeres impairs chromosome
      function, and may thus affect cell survival, we propose that telomerase activity
      is required for immortality. We have now detected this enzyme in a variety of
      immortal human cells transformed by different viruses, indicating that telomerase
      activation may be a common step in immortalization.

PMID- 8151806
TI  - Modification of the cascade model for regulation of vaccinia virus gene
      expression: purification of a prereplicative, late-stage-specific transcription
      factor.
AB  - In vivo and in vitro studies have provided evidence that vaccinia virus late gene
      transcription factors are intermediate gene products synthesized exclusively
      after DNA replication. Here, we describe an additional transcription factor (P3
      factor) that stimulates late gene transcription between 10- and 40-fold but is
      made in the absence of viral DNA replication. P3 factor activity was not detected
      either in uninfected cells or in purified virions. A > 1,500-fold purification of
      P3 factor was achieved by column chromatography of cytoplasmic extracts prepared
      from cells infected with vaccinia virus in the presence of a DNA replication
      inhibitor. P3 factor was stage specific, since it could not substitute for early
      or intermediate transcription factors. Evidence that late stage-specific
      transcription factors are made both before and after DNA replication necessitates
      a modification of the cascade model for vaccinia virus gene regulation.

PMID- 8151814
TI  - Blood lead levels of wild raccoons (Procyon lotor) from the eastern United
      States.
AB  - We analyzed 161 raccoon (Procyon lotor) blood samples obtained from New Jersey (n
      = 109), rural Pennsylvania (n = 29) and laboratory confined animals (n = 23) in
      the USA for lead content; we found significantly higher levels in the New Jersey
      raccoons (mean = 4.4 micrograms/dl, SE = 2.9). There was no difference between
      the lead levels of raccoons from the other two groups (mean = 2.6, SE = 0.5 and
      mean = 2.5, SE = 0, respectively).

PMID- 8151804
TI  - Dynamic behavior of hepatitis C virus quasispecies in patients undergoing
      orthotopic liver transplantation.
AB  - We have studied the distribution of viral sequences from the 5' noncoding region
      and from a fragment of the E2/NS2 region of the hepatitis C virus (HCV) genome in
      samples obtained before and after liver transplantation in two patients with HCV
      cirrhosis. The population of viral sequences in both regions were established by
      sequencing cloned PCR products. In both cases, the complexity of the viral
      quasispecies decreased after transplantation, although the consensus nucleotide
      and amino acid sequences remained unchanged. It is suggested that both positive
      and negative selection and random sampling events contribute substantially in
      shaping the genetic composition of HCV quasispecies and that recurrence of HCV
      infection may occur under equilibrium conditions.

PMID- 8151801
TI  - Microglial infection by a neurovirulent murine retrovirus results in defective
      processing of envelope protein and intracellular budding of virus particles.
AB  - The observation of murine retrovirus infection of microglial cells in brain
      regions expressing spongiform neurodegenerative changes suggests that these cells
      may play an important role in pathogenesis. To evaluate this potential in vitro,
      murine microglial cells were infected in mixed glial cultures with the highly
      neurovirulent murine retrovirus, FrCasE. The microglia were then isolated from
      the mixed cultures on the basis of their differential adherence and shown to be
      approximately 98% pure. The infected microglia expressed viral envelope protein
      at the plasma membrane, while viral budding was primarily intracellular.
      Evaluation of the viral envelope protein by immunoblotting indicated that the
      immunoreactive species produced was exclusively a 90-kDa precursor protein. Very
      little of the envelope protein was associated with particles released from these
      cells, and viral titers in the culture supernatant were low. Interestingly, these
      cells were still capable of infecting permissive target cells when seeded as
      infectious centers. This partially defective infection of microglial cells
      suggests a potential cellular means by which a neurovirulent retrovirus could
      disrupt normal microglia and in turn central nervous system motor system
      functioning.

PMID- 8151809
TI  - Bacteria isolated from nasal and tonsillar samples of clinically healthy Rocky
      Mountain bighorn and domestic sheep.
AB  - Nasal and tonsillar samples were collected from 14 free-ranging clinically
      healthy Rocky Mountain bighorn sheep (Ovis canadensis canadensis) and 10 domestic
      sheep (Ovis aries). We identified 194 bacterial isolates, including 101 from
      bighorn and 93 from domestic sheep. Of these isolates, 115 were gram-positive and
      79 were gram-negative. Staphylococcus species were the most numerous gram
      positive organisms and had a higher incidence in samples from domestic than from
      bighorn sheep. In contrast Streptococcus species were present in higher numbers
      in samples from bighorn sheep. Pasteurella haemolytica, the most common gram
      negative bacterium, was isolated from five of five tonsillar but from none of ten
      nasal samples of domestic sheep, and from seven of eight tonsillar and three of
      ten nasal samples of bighorn sheep. Most bacteria isolated were considered
      opportunistic pathogens. However, of the bacteria isolated, P. haemolytica, P.
      multocida, and Actinomyces pyogenes are most frequently associated with
      respiratory disease.

PMID- 8151811
TI  - Protocalliphora braueri (Diptera: Calliphoridae) induced pathogenesis in a brood
      of marsh wren (Cistothorus palustris) young.
AB  - Infestation with blow fly larvae (Protocalliphora (Trypocalliphora) braueri
      Hendel) was pathogenic to marsh wren (Cistothorus palustris) young. The mechanism
      of pathogenicity was Pseudomonas spp. infection of subdermal myiasis-induced
      lesions and subsequent sepsis. Neither internal organ involvement nor muscle
      destruction was seen on necropsy of fledglings. Multifocal hepatic necrosis was
      seen histologically and Pseudomonas sp. was isolated from myiasis sites, liver,
      and peritoneal cavities.

PMID- 8151812
TI  - Prevalence of Cryptosporidium sp. in peak density Microtus agrestis, Microtus
      oeconomus and Clethrionomys glareolus populations.
AB  - The prevalence of cryptosporidia was determined in high density populations of
      Microtus agrestis, Microtus oeconomus, and Clethrionomys glareolus in Finland.
      One of 131 M. Agrestis and one of 41 C. glareolus each were found to be infected
      with Cryptosporidium sp.; none were found in 43 Microtus oeconomus. These
      apparently healthy voles had neither signs of clinical disease nor
      histopathological changes in intestines.

PMID- 8151803
TI  - Evolution of the human immunodeficiency virus type 2 envelope gene in
      preimmunized and persistently infected rhesus macaques.
AB  - The V3 and V4 domains of human immunodeficiency virus type 2 (HIV-2) env genes
      from 14 rhesus macaques experimentally infected by HIV-2 SBL6669/H5 were
      sequenced. No variation was observed in viral sequences from sera and from
      uncultured peripheral blood mononuclear cells during primary infection. The first
      mutations were detected 17 months after infection; they mainly concerned the
      region between the V3 and V4 domains and not those domains themselves, which are
      known to be hypervariable, suggesting that variation of V3 is a late event of HIV
      infection.

PMID- 8151807
TI  - The open reading frame I (ORF I)/ORF II part of the human T-cell leukemia virus
      type I X region is dispensable for p40tax, p27rex, or envelope expression.
AB  - The X region of the human T-cell leukemia virus type I contains the second coding
      exon of the tax and rex regulatory proteins (open reading frame IV [ORF IV] and
      ORF III, respectively), as well as coding regions for more recently described
      proteins, p30II (or the tof protein) and p13II in ORF II and the putative rof
      protein and p12I in ORF I. Deletions and transcomplementation experiments showed
      that expression of the envelope, as well as that of the tax and rex proteins, was
      independent of the proteins encoded in the ORF I/ORF II region. Furthermore,
      p30II and p12I proteins could not replace the rex protein in a rex-dependent
      envelope or Gag protein expression system.

PMID- 8151805
TI  - Distribution of mouse mammary tumor virus in Asian wild mice.
AB  - Several groups of wild mice (Mus musculus) were captured from eight different
      locations in Asia and bred for several generations in a facility free of any
      laboratory strains of mice carrying mouse mammary tumor virus (MMTV). The
      distribution of endogenous MMTV proviral sequences in the liver tissues of these
      mice was investigated by using Southern blot hybridizations. Four categories of
      mice were identified. Mice originating from Bogor, Indonesia (Cas-Bgr); He-mei,
      Taiwan (Cas-Hmi/1); and Malaysia (Cas-Mal) were found to carry an endogenous MMTV
      provirus consisting of the env, gag-pol, and long terminal repeat sequences. Mice
      captured from Kojuri, Republic of Korea (Sub-Kjr); Nagoya, Japan (Mol-nag); and
      three Chinese provinces, Shanghai (Sub-Shh), Beijing (Sub-Bjn), and Jiayuguang
      (Sub-Jyg/1), appeared to carry defective proviruses. Some mice originating from
      He-mei (Cas-Hmi/2) and Jiayuguang (Sub-Jyg/2) were found to be completely free of
      endogenous MMTV. Interestingly, however, the Sub-Jyg/2 mice, after several
      generations of inbreeding, were found, unlike all of the other subspecies that we
      examined in the present study, to develop mammary tumors at a high incidence (80
      to 90%) with a short period of latency. Electron microscopic examination of the
      mammary glands and mammary tumors of these mice revealed the presence of numerous
      intracytoplasmic A, immature, budding, and mature B particles. Furthermore, the
      mammary tumors were found to contain MMTV proviral sequences. It seems,
      therefore, that Sub-Jyg/2 mice carry an exogenous MMTV which contributes to their
      developing mammary tumors.

PMID- 8151810
TI  - A serologic survey of selected viral and bacterial diseases of European wild
      hogs, Great Smoky Mountains National Park, USA.
AB  - Blood samples were collected from 108 wild hogs (Sus scrofa) from the Great Smoky
      Mountains National Park (GSMNP), USA, February to July 1990. We found no
      antibodies for swine brucellosis, pseudorabies, bovine virus diarrhea virus or
      porcine rotavirus infection. Antibody titers to porcine parvovirus were found in
      15 (14%) samples and antibody to one or more leptospiral serovars was found in 48
      (44%) samples. Thirty-nine (89%) of the 44 positive samples reacted to all five
      leptospiral serovars tested.

PMID- 8151808
TI  - American Urological Association 89th annual meeting. San Francisco, California,
      May 14-19, 1994. Abstracts.

PMID- 8151815
TI  - Use of tiletamine and zolazepam to immobilize captive Iberian wolves (Canis
      lupus).
AB  - A mixture of tiletamine and zolazepam (Zoletil) was used to immobilize 29 captive
      born Iberian wolves. Based on their excitability during handling procedures the
      animals were categorized as excited (n = 15) and unexcited (n = 14). We observed
      differences in the responses of these groups to the drugs. Although immobilized
      with higher doses (mean +/- SD of 6.94 +/- 2.13 versus 5.04 +/- 1.74 mg/kg for
      the unexcited) the excited individuals had an irregular and less predictable
      response, with five individuals needing additional dosages in the excited group
      compared to one animal in the unexcited group. Arousal time and duration of
      immobilization of excited wolves was not correlated to initial drug doses, but
      was in unexcited animals; the excited group had a poorer thermal regulation.
      Differences in arousal time and duration could be the a result of the different
      doses used. Excited wolves were older than unexcited (5.4 +/- 3.07 versus 2.86 +/
      2.11 years, respectively). For captive wolves, doses of about 5 mg/kg are
      recommended for non-excited and 10 mg/kg for excited individuals.

PMID- 8151816
TI  - Postpartum immobilization of adult female moose using xylazine, ketamine and
      yohimbine hydrochlorides.
AB  - Twenty-two free-ranging adult female moose (Alces alces) were immobilized with a
      1:4 mixture of xylazine hydrochloride (XH) and ketamine hydrochloride (KH). Mean
      (SD) dosages/animal for XH and KH were 419 (148) and 1565 (433) mg, respectively.
      Mean (SD) induction time was 18.4 (9.7) minutes. Reversal with yohimbine
      hydrochloride using a mean dosage of 83 mg/animal resulted in a mean (SD)
      recovery time of 22.8 (28.5) minutes.

PMID- 8151813
TI  - Background prevalence of tetracycline-like fluorescence in teeth of free ranging
      red foxes (Vulpes vulpes), striped skunks (Mephitis mephitis) and raccoons
      (Procyon lotor) in Ontario, Canada.
AB  - We collected and examined teeth from 3406 red foxes (Vulpes vulpes) collected in
      Ontario, Canada, from 1978 to 1986, prior to large scale rabies vaccine baiting.
      We found tetracycline-like fluorescence in five (0.2%) of the samples. Also, we
      observed similar fluorescences in five (0.4%) of 1103 striped skunks (Mephitis
      mephitis) and in six (0.8%) of 744 raccoons (Procyon lotor). The low prevalence
      of such marks would not appear to invalidate the use of tetracycline as a marking
      agent in vaccine baiting trials.

PMID- 8151818
TI  - Effects of modified Cary and Blair medium on recovery of nonhemolytic Pasteurella
      haemolytica from Rocky Mountain bighorn sheep (Ovis canadensis canadensis)
      pharyngeal swabs.
AB  - Modified Cary and Blair transport medium (MCB) was evaluated for recovery of
      Pasteurella spp. from pharyngeal swabs of healthy Rocky Mountain bighorn sheep
      (Ovis canadensis canadensis). In experiment one, three pharyngeal swabs were
      collected from each of 25 bighorns. Pasteurella haemolytica was recovered from 21
      of 25 swabs tested almost immediately and from 16 of 25 swabs held in MCB medium
      at about 22 C for 24 hr before testing (P > 0.10). Recovery of P. haemolytica
      decreased (P < 0.005) to 1 of 25 when swabs were held in MCB medium at about 22 C
      for 48 hr before testing. In experiment two, four pharyngeal swabs were collected
      from each of ten bighorns and held in MCB medium at about 5 C for < or = 5, 24,
      48, or 72 hr prior to testing. Recovery was unaffected by storage at 5 C; P.
      haemolytica was isolated from all 40 of these samples. All Pasteurella spp.
      isolates were nonhemolytic P. haemolytica. In experiment one, most isolates were
      serotype 4; in experiment two, serotype 3 was most common. We propose that MCB
      medium is effective for transporting bighorn sheep pharyngeal swabs for P.
      haemolytica screening because it imposes minimal or no effect on recovery when
      held < or = 24 hr at 22 C or < or = 72 hr at 5 C.

PMID- 8151817
TI  - Intestinal volvulus in a bowhead whale, Balaena mysticetus.
AB  - An adult female bowhead whale, Balaena mysticetus, from the Beaufort Sea, Alaska
      (USA), had necrosis of a well-demarcated portion of the mid-jejunum and adjacent
      mesentery, accompanied by fibrinous peritonitis. The veins within the mesentery
      adjacent to the affected intestine were severely dilated and hyperemic. There
      were no perforations of the gastrointestinal tract, nor any thromboses within the
      mesenteric veins. Death appeared due to the sequelae of intestinal volvulus and
      infarction; reduction of the displacement presumably occurred during handling of
      the animal.

PMID- 8151820
TI  - Sarcocystis sp. in wading birds (Ciconiiformes) from Florida.
AB  - Sarcocysts were found in striated muscle of 21 adult wading birds among 145
      examined grossly and 70 examined histologically (calculated prevalence = 24%),
      and in none of 332 immature wading birds examined from Florida (USA). Six of 12
      species of ciconiforms were infected (Ardea herodias, Casmerodius albus, Egretta
      caerulea, Nyctanassa violacea, Butorides striatus, Eudocimus albus). Cysts were
      filamentous, usually extended the entire length of the muscle fiber, and were
      visible grossly in 33% of the positive cases. We concluded from ultrastructural
      examination of cysts that the same species of Sarcocystis may occur in all
      species of wading birds in Florida; however, two cyst diameters were noted that
      appeared to differ in their distribution by host species.

PMID- 8151819
TI  - Experimental infection of Columbian black-tailed deer with the Lyme disease
      spirochete.
AB  - The course of Borrelia burgdorferi-infection in Columbian black-tailed deer.
      (Odocoileus hemionus columbianus), its effect on the health of these animals, and
      their reservoir competence for fleas were evaluated experimentally. Four yearling
      females inoculated intramuscularly with 10(8) organisms of the CA4 strain of B.
      burgdorferi, and two yearling males unexposed to spirochetes, were monitored
      daily for 3 mo. Spirochetes were reisolated from the blood of three does at 14 or
      70 days postinjection, and from several tissues of the fourth doe at necropsy.
      Considerable antigenic heterogeneity was observed among the reisolates as
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Only two
      of the four infected deer developed significant antibodies (> or = 1:128) to B.
      burgdorferi with titers persisting for < or = 2 mo. Hematological values were
      highly variable and the degree of variation observed was much greater than that
      reported previously for Columbian black-tailed deer or other subspecies of mule
      deer. Infected deer did not manifest signs of Lyme disease. On histologic
      examination of eight tissues per deer, we observed a minimal hepatic lesion in
      all animals exposed to B. burgdorferi. No spirochetes were detected in 367 fleas
      (Pulex irritans) that had naturally infested these deer; thus this flea probably
      is an inefficient host of B. burgdorferi.

PMID- 8151821
TI  - Hematozoa of wood ducks (Aix sponsa) in Missouri.
AB  - We examined 371 wood ducks (Aix sponsa) for hematozoa from two localities in
      Missouri (USA) in 1989 and 1990. Thirty-seven (10%) harbored one or more species
      of blood parasites. Haemoproteus nettionis was the most common parasite,
      occurring in 36 (10%) of the birds. Leucocytozoon simondi was found in two (0.5%)
      and microfilaria occurred in five (1%) of the wood ducks examined. Infections
      were more prevalent in adults (18%) than in immature birds (2%). There was no
      difference in prevalence between sex, location, or year. Based on seasonal
      prevalence, transmission probably did not occur at either location in the summer.
      Increased prevalence in the winter samples occurred after northern wood ducks
      migrated into the sample areas.

PMID- 8151822
TI  - Experimental toxoplasmosis in pheasants (Phasianus colchicus).
AB  - Sixteen 6-mo-old battery-reared ring-necked pheasants (Phasianus colchicus) were
      inoculated orally with 10(5) (group A, ME 49 strain, five birds), 10(4) (group B,
      ME 49 strain, six birds) and 10(4) (group C, GT-1 strain, five birds) Toxoplasma
      gondii oocysts. The pheasants in groups A and B remained clinically normal. One
      of the pheasants in group C died 19 days after inoculation (DAI); T. gondii was
      found in histological sections of brain and heart and encephalitis, myocarditis
      and enteritis were the main lesions. Toxoplasma gondii was isolated by bioassays
      from pooled tissues of five of six pheasants in group B killed 36 DAI. Toxoplasma
      gondii was isolated from the brains, hearts and skeletal muscles of each of the
      four pheasants inoculated with the GT-1 strain (group C), and from the brains of
      four, hearts of three and skeletal muscles of four of five pheasants inoculated
      with the ME 49 strain (group A). All pheasants developed high (1: 1,600-1:25,600)
      antibody titers to T. gondii in the modified agglutination test (MAT) 36 to 68
      DAI. Antibody titers detected with the MAT were higher than those detected in the
      indirect hemagglutination and latex agglutination tests. Antibodies were not
      detected in 1:4 dilution of pheasant sera with the Sabin-Feldman dye test.

PMID- 8151823
TI  - Viability of Notocotylus attenuatus (Trematoda: Notocotylidae) metacercariae
      under adverse conditions.
AB  - The viability of Notocotylus attenuatus metacercariae was 80% at 20 wk post
      encystment (PE) and decreased to 10% at 24 wk PE. Cyst viability was influenced
      by the duration of cercarial swimming activity prior to encystment, by the
      occurrence of cyst associations, and by the type of cyst storage. This is the
      first report on cyst associations formed by Notocotylidae cercariae. Cyst
      associations were formed only by cercariae encysting shortly after their
      emergence from snails. In cyst associations metacercariae did not overlap, but
      were separated by regular distances ranged from 20.4 to 24.5 microns mean = 22.3
      microns, SE = 0.41. The mucoid materials which formed the external cyst wall
      covered the areas between parasites seven if distances were comparable with the
      cyst size. In cyst associations, metacercariae in the water and those located
      close to the water were viable up to 24 wk PE. Cercariae with extended swimming
      activity did not form associations even when present in numbers, < or = 50
      cercariae per cm3. The cysts established by these cercariae had a thin external
      cyst wall, and were not viable by 12 wk PE.

PMID- 8151824
TI  - Antibody prevalence of eight ruminant infectious diseases in California mule and
      black-tailed deer (Odocoileus hemionus).
AB  - We tested 276 sera from 18 free-ranging black-tailed and mule deer (Odocoileus
      hemionus) herds in California (USA) collected from 1987 to 1991 in five
      biogeographical habitat types, for antibodies against eight infectious disease
      agents. Overall antibody prevalence was 56% for Anaplasma marginale, 31% for
      Borrelia burgdorferi, 16% for bluetongue virus serotype 17, 15% for epizootic
      hemorrhagic disease virus, 7% for Coxiella burnetii and Toxoplasma gondii,
      respectively, and 0% for bovine leukosis virus and caprine arthritis/encephalitis
      virus, respectively. Antibodies against Lyme borreliosis and anaplasmosis were
      found in deer throughout California, but antibodies against bluetongue and
      epizootic hemorrhagic disease were most prevalent in deer from southern
      California.

PMID- 8151825
TI  - Lead poisoning and other causes of mortality in trumpeter (Cygnus buccinator) and
      tundra (C. columbianus) swans in western Washington.
AB  - Lead poisoning and other causes of mortality of 115 trumpeter (Cygnus buccinator)
      and 21 tundra (C. columbianus) swans from northwestern Washington (USA) from 1986
      to 1992 are reported. Necropsies were performed on all 136 swans, liver lead
      analysis conducted on 110, and differentiation between lead and steel shot
      pellets recovered from gizzards in 97 swans. Shot pellets were detected in 44
      (32%) of 136 gizzards. Lead shot was recovered from 32 (33%) of 97 gizzards and
      steel shot from 16 (16%). Mean intensity of lead shot in gizzards was nearly five
      times greater than steel shot. Thirty-nine (35%) of 110 livers had lead
      concentrations diagnostic of lead poisoning (> 6 ppm, wet weight). Mean (+/- SE)
      weight for 61 non-lead poisoned trumpeter swans was 9.8 (+/- 0.30) kg,
      significantly heavier (P < 0.05) than 30 lead poisoned trumpeters (mean = 6.8 +/-
      0.23 kg). There was no significant difference (P > 0.05) in weights between lead
      poisoned (n = 9) and non-lead poisoned (n = 12) tundra swans. Lead poisoning was
      the primary cause of death, accounting for 29% of the mortalities. Other causes
      of mortality identified were aspergillosis (17%), illegally shot (11%), and other
      traumatic factors (12%). The cause of death for 43 swans was not determined. Lead
      poisoning from the ingestion of lead shot continues to be a principal cause of
      mortality in swans overwintering in northwestern Washington.

PMID- 8151826
TI  - Immobilization of the endangered Iberian lynx with xylazine- and ketamine
      hydrochloride.
AB  - A combination of the dissociative anesthetic ketamine hydrochloride (KH) and the
      sedative xylazine hydrochloride (XH) was used to immobilize 31 wild Iberian lynx
      (Felis pardina) 45 times at Donana National Park, Spain. A mean (+/- SE) dose of
      4.6 (+/- 0.2) mg/kg KH and 4.0 (+/- 0.2) mg/kg XH resulted in mean (+/- SE)
      induction time of 5.6 (+/- 0.3) min and mean (+/- SE) first reaction time of 59.3
      (+/- 6.5) min. Convulsions occurred four times (9%), but with no noteworthy
      consequences.

PMID- 8151827
TI  - The hematological profile of the mountain gazelle (Gazella gazella): variations
      with sex, age, capture method, season, and anesthesia.
AB  - Hematological parameters were measured in 408 blood samples collected over a 30
      mo period from 254 captive mountain gazelles (Gazella gazella) in Saudi Arabia.
      We evaluated the influence of sex, age, capture method, and season, on these
      parameters. Evaluations also were made with a small number of anesthetized
      animals. Males had a significantly higher mean corpuscular volume (MCV) and mean
      corpuscular hemoglobin (MCH) than females. There was no observed neutrophil:
      lymphocyte ratio shift for either sex during the first months of life. The
      effects of different capture methods generally were similar in males and females
      and included a significantly lower MCV and MCH after quick capture. Animals
      undergoing slow capture had a significantly lower mean corpuscular hemoglobin
      concentration (MCHC), and very pronounced stress neutrophilia. We propose that
      this stress neutrophilia caused the permanently high neutrophil: lymphocyte ratio
      (62:36 average for all gazelles tested) and the lack of a neutrophil: lymphocyte
      shift in young animals. Erythrocyte counts were significantly higher in summer,
      while packed cell volume and hemoglobin concentration were the same in summer and
      winter; thus there was a significantly lower MCV and MCH, and a significantly
      higher MCHC in summer in both sexes. Fibrinogen varied significantly by sex, age,
      capture method, and anesthesia.

PMID- 8151828
TI  - Mineral content of Louisiana white-tailed deer.
AB  - Water, lipid, and mineral composition were determined for metacarpals, phalanges,
      livers, and antlers from 219 free-ranging white-tailed deer (Odocoileus
      virginianus) collected on six properties in East Feliciana Parish, Louisiana
      (USA) to provide baseline data and to identify sources of composition variation.
      Metacarpal and phalangeal composition varied primarily with deer age; liver
      composition varied with deer sex.

PMID- 8151829
TI  - Evaluation of Hawaiian green turtles (Chelonia mydas) for potential pathogens
      associated with fibropapillomas.
AB  - Thirty-two juvenile green turtles (Chelonia mydas) were captured alive in Kaneohe
      Bay, Island of Oahu, Hawaii, during September 1991. Ten of the turtles sampled
      were afflicted with green turtle fibropapillomatosis (GTFP) in varying degrees of
      severity. Virus isolation attempts were negative in all individuals. Using
      nasopharyngeal and cloacal swabs, we isolated 28 Gram negative bacteria, five
      Gram positive cocci, Bacillus spp., and diphtheroids. The most common isolates
      included Pseudomonas fluorescens (68%), P. putrefaciens (66%), Vibrio
      alginolyticus (50%), non-hemolytic Streptococcus (50%), V. damsela (47%), and V.
      fluvialis (47%). Chlamydial antigen was detected in four of the turtles sampled.
      The primary lesions in animals with GTFP were hyperplasia of squamous epithelial
      cells and mesodermal proliferation with a marked degree of orthokeratotic
      hyperkeratosis. Mites, leeches, and other organisms were associated with the
      surface of papilloma lesions. The etiologic agent of GTFP was not isolated.

PMID- 8151830
TI  - Serologic survey of giant pandas (Ailuropoda melanoleuca), and domestic dogs and
      cats in the Wolong Reserve, China.
AB  - Sera from captive and recently rescued giant pandas (Ailuropoda melanoleuca) in
      the Wolong Reserve, China, were examined by serum neutralization or
      hemagglutination inhibition for antibodies to canine distemper virus (CDV),
      canine coronavirus (CCV), canine herpesvirus (CHV), pseudorabies virus (PRV),
      canine adenovirus type 2 (CAV), and canine parvovirus (CPV). Serum samples from
      village domestic dogs and cats, which run free throughout the reserve also were
      examined. Antibodies against CPV were detected in six of eight giant pandas and
      all dogs and cats tested. The origin of the virus was not determined. Two of
      eight giant pandas and two of seven dogs had CDV antibody titers. Three of eight
      pandas and three of seven dogs had CCV antibody titers. Four of eight pandas and
      two of seven dogs had CAV titers; the titers in dogs were very high. No pandas or
      dogs had evidence of exposure to CHV or PRV.

PMID- 8151831
TI  - Neutralizing antibodies to phocine distemper virus in Atlantic walruses (Odobenus
      rosmarus rosmarus) from Arctic Canada.
AB  - The first evidence of phocine distemper virus (PDV) infection in Atlantic
      walruses (Odobenus rosmarus rosmarus) from Nottingham Island, Northwest
      Territories, Canada, is reported. Blood samples were collected from three male
      walruses killed by Inuit hunters in the fall of 1990. Differential virus
      neutralization test for each animal yielded higher titers against PDV than
      against other members of the Morbillivirus genus including canine distemper,
      peste des petits ruminants, rinderpest and measles viruses. Thus, PDV infection
      may be enzootic in walruses of the eastern Canadian Arctic.

PMID- 8151832
TI  - Detection of canine distemper viral antigen in foxes (Vulpes vulpes) in
      northwestern Spain.
AB  - We describe the lesions of natural distemper in red foxes (Vulpes vulpes) in
      Spain. The avidin-biotin-peroxidase complex (ABC) technique and a monoclonal
      antibody against the nucleocapsid protein of canine distemper virus were
      successfully used to confirm canine distemper diagnosis.

PMID- 8151833
TI  - Serologic detection of bluetongue virus infection of black-tailed deer:
      comparison of serum neutralization, agar gel immunodiffusion, and competitive
      ELISA assays.
AB  - Three adult black-tailed deer (Odocoileus hemionus columbianus) and four fawns
      were inoculated with bluetongue virus (BTV) serotype 10 or 17, or epizootic
      hemorrhagic disease virus (EHDV) serotype 1. Animals were bled at irregular
      intervals thereafter and the presence of virus-specific antibodies in serum
      determined by agar gel immunodiffusion (AGID), serum neutralization (SN) and
      competitive enzyme-linked immunosorbent assay (C-ELISA) tests. Serum antibodies
      to BTV were detected in all three tests for 692 days after inoculation (DAI) of
      adult deer, but both the SN and AGID tests gave either erroneous or misleading
      results. Serum from one deer was negative by the AGID test at 409 DAI with BTV-10
      but was positive at 248 and 692 DAI; also one adult and one fawn had antibodies
      by the SN test to serotypes of BTV with which they were not inoculated. The AGID
      test for EHDV had false positive results with some sera from animals inoculated
      only with BTV, and it consistently had false negative results with serum samples
      collected from an EHDV-inoculated deer at 140 DAI and thereafter. The C-ELISA was
      the most useful test for the detection of antibodies to BTV because it rapidly
      gave quantitative and accurate results.

PMID- 8151834
TI  - AIDS research coordination abetted.

PMID- 8151835
TI  - Are there too many US transplantation centers? Some experts suggest fewer,
      cheaper, and better.

PMID- 8151836
TI  - Clinical medicine meets forensic sciences.

PMID- 8151837
TI  - From the Food and Drug Administration.

PMID- 8151838
TI  - From the Centers for Disease Control and Prevention. Health risk behaviors among
      adolescents who do and do not attend school--United States, 1992.

PMID- 8151839
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States and worldwide, 1993-94 season, and composition of the 1994-95
      influenza vaccine.

PMID- 8151841
TI  - A piece of my mind. A purely cosmetic procedure.

PMID- 8151840
TI  - From the Centers for Disease Control and Prevention. Bacillus cereus food
      poisoning associated with fried rice at two child day care centers--Virginia,
      1993.

PMID- 8151842
TI  - Lipoprotein(a) and risk of myocardial infarction.

PMID- 8151843
TI  - Lipoprotein(a) and risk of myocardial infarction.

PMID- 8151844
TI  - Work disability and workers' compensation.

PMID- 8151845
TI  - Isolating fetal trophoblast cells for prenatal genetic diagnosis.

PMID- 8151846
TI  - Depression and survival following myocardial infarction.

PMID- 8151847
TI  - Depression and survival following myocardial infarction.

PMID- 8151848
TI  - Depression and survival following myocardial infarction.

PMID- 8151849
TI  - Depression and survival following myocardial infarction.

PMID- 8151850
TI  - Comparison of long-term prognosis of patients with AIDS treated and not treated
      with zidovudine. AIDS in Europe Study Group.
AB  - OBJECTIVE: To determine the association between elapsed time since starting
      zidovudine and survival in patients with acquired immunodeficiency syndrome
      (AIDS). DESIGN: Inception cohort and observational study of patients treated and
      not treated with zidovudine. SETTING: Fifty-one centers in 17 European countries.
      PATIENTS: A total of 4484 patients diagnosed as having AIDS from 1979 to 1989 who
      survived their initial AIDS-defining event and who had not started zidovudine
      before AIDS diagnosis. MAIN OUTCOME MEASURES: Use of zidovudine and mortality.
      RESULTS: Among patients who did not receive zidovudine, the death rate was
      approximately constant for the first 5 years after AIDS diagnosis. For patients
      treated with zidovudine, the death rate within the first year since starting
      zidovudine was markedly lower than for untreated patients who had developed AIDS
      at the same time (relative rate, 0.47; 95% confidence interval [CI], 0.42 to
      0.51). For longer times since starting zidovudine, the association with reduced
      mortality rate was diminished, and for patients surviving more than 2 years since
      starting zidovudine, the death rate was greater than for untreated patients who
      had developed AIDS at the same time (relative rate, 1.35; 95% CI, 1.15 to 1.58).
      Adjustment for other prognostic factors failed to substantially affect this
      observation. CONCLUSIONS: When initiated after the time of AIDS diagnosis,
      zidovudine was associated with improved prognosis but for no more than 2 years
      after starting therapy.

PMID- 8151851
TI  - Body mass index, weight change, and risk of mobility disability in middle-aged
      and older women. The epidemiologic follow-up study of NHANES I.
AB  - OBJECTIVE: As disability is highly prevalent among older women, is costly, and
      affects the quality of life, preventable causes of disability must be identified.
      In this study, we investigated the relationship between the body mass index
      (BMI), weight change, and the onset of disability in older women. DESIGN:
      Prospective cohort study. SETTING: The nationally representative US epidemiologic
      follow-up study of the National Health and Nutrition Examination Survey (NHANES)
      I (1971 through 1987). PATIENTS: White women classified as young-old (mean age 60
      years at baseline, mean age 65 years at follow-up) and old-old (mean age 76 years
      at baseline, mean age 80 years at follow-up). MAIN OUTCOME MEASURES: The relative
      odds for the onset of mobility disability associated with tertiles of past BMI
      (measured 8 to 16 years prior to disability ascertainment) and current BMI
      (measured 2 to 5 years prior to disability ascertainment) and with weight change
      between the two weight measurements. RESULTS: In both cohorts, women in the high
      past BMI group (> 27 in the young-old and > 28.1 in the old-old cohort) had a
      twofold increase in the risk for disability compared with women in the low past
      BMI group. High current BMI was as strongly related as past BMI to risk of
      disability in the young-old women; it was not as strong a predictor in old-old
      women. In the old-old group only, women who experienced a weight loss of more
      than 5% had a twofold increase in risk of disability compared with weight-stable
      women. These results were adjusted for age, smoking, education, and study time
      and were not importantly modified with the addition into the models of single or
      multiple health conditions. CONCLUSIONS: These prospective data suggest that high
      BMI is a strong predictor of long-term risk for mobility disability in older
      women and that this risk persists even to very old age. However, the paradoxical
      increase in risk associated with weight loss in the old-old women requires
      further study. Programs to prevent overweight may have potential for decreasing
      disability in women.

PMID- 8151852
TI  - Oral contraceptives and renal and retinal complications in young women with
      insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To evaluate the effects of oral contraceptives (OCs) as a possible
      risk factor for early diabetic renal and/or retinal complications. DESIGN: A
      retrospective case-control study. SETTING: A university hospital diabetes clinic.
      PARTICIPANTS: Forty-three diabetic women who used OCs for 1 year or longer (mean,
      3.4 years; range, 1.0 to 7.0 years) were compared with a computer-matched control
      group of 43 diabetic women who never used OCs. MAIN OUTCOME MEASURES: Hemoglobin
      A1c levels, albumin excretion rates, and mean retinopathy scores. RESULTS: The
      mean +/- SEM age and duration of diabetes were 22.7 +/- 0.5 years (range, 17.1 to
      30.5 years) and 13.8 +/- 0.8 years, respectively, for the study group. The mean
      longitudinal hemoglobin A1c values were similar for study subjects and control
      subjects. The final mean albumin excretion rates, reflecting diabetic renal
      damage, and the mean eye grades were not significantly different between the
      groups. CONCLUSIONS: The use of OCs among young women with insulin-dependent
      diabetes mellitus does not pose an additional risk for the development of early
      diabetic retinopathy and/or nephropathy.

PMID- 8151853
TI  - Understanding and using the medical subject headings (MeSH) vocabulary to perform
      literature searches.
AB  - The United States National Library of Medicine's (NLM) MEDLINE database is the
      largest and most widely used medical bibliographic database. MEDLINE is manually
      indexed with NLM's Medical Subject Headings (MeSH) vocabulary. Using MeSH, a
      searcher can potentially create powerful and unambiguous MEDLINE queries. This
      article reviews the structure and use of MeSH, directed toward the nonexpert, and
      outlines how MeSH may help resolve a number of common difficulties encountered
      when searching MEDLINE. The increasing importance of the MEDLINE database as an
      information resource and the trend toward individuals performing their own
      bibliographic searches makes it crucial that health care professionals become
      familiar with MeSH.

PMID- 8151854
TI  - Effect of inhaling heated vapor on symptoms of the common cold.
AB  - OBJECTIVE: To test the efficacy of steam inhalation in treating common cold
      symptoms. DESIGN: An in vitro study determined the temperature that inactivated
      rhinovirus: a temperature of 43 degrees C lasting at least 1 hour was needed. We
      then conducted a double-blind, placebo-controlled, randomized in vivo study.
      SETTING: The virology laboratory and the outpatient department of the Cleveland
      (Ohio) Clinic Foundation. PATIENTS: Sixty-eight Cleveland Clinic employee
      volunteers with symptoms of the common cold at the time of enrollment.
      INTERVENTION: A single 60-minute treatment was given to the volunteers. The steam
      treatment group (n = 32) received 40 L/min of heated saturated air that raised
      the intranasal temperature to 43 degrees C. The placebo group (n = 36) received 2
      L/min of ambient air at 20 degrees C to 24 degrees C. MAIN OUTCOME MEASURES:
      Subjective symptom scores for nasal congestion, nasal drainage, and sneezing and
      objective measures of nasal resistance were studied during a 7-day follow-up
      observation period. RESULTS: There were no significant differences in daily
      symptom scores between the groups (P = .59 to .83). The only statistically
      significant differences between the groups were lower nasal resistances at
      baseline in the steam group (P = .04) and percent improvement in nasal resistance
      favoring the placebo group on day 7 (P = .01). However, these differences were of
      questionable clinical significance. CONCLUSION: We conclude that steam inhalation
      treatment had no beneficial effect on the cold symptoms of our volunteers.

PMID- 8151855
TI  - Effect of inhalation of hot humidified air on experimental rhinovirus infection.
AB  - OBJECTIVE: Nasal inhalation of steam has been proposed as treatment of viral
      colds on the assumption that increased intranasal temperature will inhibit
      replication of rhinovirus (RV). The effect of steam inhalation on RV shedding by
      infected volunteers was examined in this study. DESIGN: Randomized controlled
      trial. Volunteers experimentally infected with RV were treated with machine
      generated humidified air, which was either hot (active) or at room temperature
      (placebo). Viral shedding was assessed over the 4 days following treatment.
      SETTING: Local hotel. PARTICIPANTS: Twenty volunteers from the university
      community who were susceptible to the challenge virus. INTERVENTION: Two 30
      minute intranasal treatments, the first at 24 hours after inoculation and the
      second at 48 hours. The temperature of active vapor was 42 degrees C to 44
      degrees C and of placebo vapor was 22 degrees C. MAIN OUTCOME MEASURES: Viral
      titers in nasal washings on each of 5 days following inoculation. RESULTS: Mean
      viral titers prior to the first treatment were 10(1.7) tissue culture infectious
      doses per milliliter in the active group and 10(1.5) in the placebo group. Mean
      titers for the next 4 days were 10(1.7), and 10(1.7), 10(1.2), and 10(0.9)/mL in
      the active group and 10(1.8), 10(1.9), 10(1.6), and 10(0.7)/mL in the placebo
      group (no significant difference). The proportion of volunteers who shed virus on
      each day was also similar in the two groups. CONCLUSION: Two nasal inhalation
      treatments with steam had no effect on viral shedding in volunteers with
      experimental RV colds.

PMID- 8151856
TI  - The rational clinical examination. Clinical assessment of stroke.

PMID- 8151857
TI  - Effectiveness of zidovudine in treatment of advanced HIV infection.

PMID- 8151858
TI  - The common cold. Cold water on hot news.

PMID- 8151859
TI  - A piece of my mind. A father's eyes.

PMID- 8151860
TI  - Health and justice professionals set goals to lessen domestic violence.

PMID- 8151861
TI  - Recommendations for antioxidants: how much evidence is enough?

PMID- 8151862
TI  - Coalition seeks drop in hypertensive disorders.

PMID- 8151863
TI  - From the Centers for Disease Control and Prevention. Physical violence during the
      12 months preceding childbirth--Alaska, Maine, Oklahoma, and West Virginia, 1990
      1991.

PMID- 8151864
TI  - From the Centers for Disease Control and Prevention. Escherichia coli O157:H7
      outbreak linked to home-cooked hamburger--California, July 1993.

PMID- 8151865
TI  - From the Centers for Disease Control and Prevention. Epidemic neuropathy--Cuba,
      1991-1994.

PMID- 8151866
TI  - Retransplantation of scarce organs: the ethical lessons.

PMID- 8151867
TI  - Critical oxygen delivery in patients with sepsis.

PMID- 8151869
TI  - Randomized clinical trials in single patients.

PMID- 8151868
TI  - Randomized clinical trials in single patients.

PMID- 8151870
TI  - HIV testing: AMA code of ethics.

PMID- 8151871
TI  - Organochlorines, breast cancer, and GATT.

PMID- 8151872
TI  - Association between newborn birth weight and prenatal care for cocaine users.

PMID- 8151873
TI  - Treatment differences and other prognostic factors related to breast cancer
      survival. Delivery systems and medical outcomes.
AB  - OBJECTIVE: To determine differences in and relative importance of treatment
      modalities by hospital type and their effect on survival of breast cancer
      patients. DESIGN: Cohort of population-based cancer registry breast cancer
      patients diagnosed from 1984 through 1990. The analysis was done within this
      cohort, stratified by hospital type and treatment modality. SETTING: Orange
      County, California, residents diagnosed and treated for breast cancer in 126
      hospitals (small community, large community, health maintenance organization
      [HMO], or teaching). PATIENTS: A total of 5892 non-Hispanic white women with no
      known prior cancer and with localized or regional, histologically confirmed
      breast cancer. MAIN OUTCOME MEASURES: Effects of treatment modality and hospital
      type on survival. Adjustments for differences in age, tumor size, number of
      positive lymph nodes, and histology were included in the analysis. RESULTS: Use
      of recommended breast-conserving surgery (BCS) was greatest among teaching
      hospitals, where more than 50% of patients with localized disease received BCS
      between 1988 and 1990 and 40% to 50% with regional disease received BCS between
      1984 and 1990. At nonteaching hospitals, 30% or less of patients received BCS
      between 1984 and 1989, regardless of stage. Rates of survival after BCS were at
      least as good as rates of survival after total mastectomy, other factors being
      equal. Survival rates varied by hospital type for patients with localized
      disease, with significantly better rates at large community hospitals and
      significantly worse rates at HMO hospitals in comparison with small hospitals.
      Patients with regional disease at large hospitals had a significant survival
      advantage. CONCLUSIONS: Greater use of BCS is strongly urged. Overall, large
      community hospitals had significantly better survival rates than small community
      and HMO hospitals. Further follow-up will determine if treatment and survival
      differences by hospital type persist.

PMID- 8151874
TI  - Health care for black and poor hospitalized Medicare patients.
AB  - OBJECTIVE: To analyze whether elderly patients who are black or from poor
      neighborhoods receive worse hospital care than other patients, taking account of
      hospital effects and using validated measures of quality of care. DESIGN: We
      compare quality of care provided to insured, hospitalized Medicare patients who
      are black or live in poor neighborhoods as compared with others, using simple and
      multivariable comparisons of clinically detailed measures of sickness at
      admission, quality, and outcomes. SETTING: Two hundred ninety-seven acute care
      hospitals in 30 areas within five states. PATIENTS OR OTHER PARTICIPANTS: The
      sample includes a nationally representative sample of 9932 patients 65 years of
      age or older who lived at home prior to hospitalization for congestive heart
      failure, acute myocardial infarction, pneumonia, or stroke. INTERVENTIONS: This
      was an observational study. MAIN OUTCOME MEASURES: Processes of care, length of
      stay, instability at discharge, discharge destination, and mortality. RESULTS:
      Within rural, urban nonteaching, and urban teaching hospitals, patients who are
      black or from poor neighborhoods have worse processes of care and greater
      instability at discharge than other patients (P < .05). However, this worse
      quality is offset by patients who are black or from poor neighborhoods being 1.8
      times more likely to receive care in urban teaching hospitals that have been
      shown to provide better quality of care (P < .001). Because these patients
      receive more of their care in better-quality hospitals, there are no overall
      differences in quality by race and poverty status. Death rates did not vary by
      race or poverty status. CONCLUSIONS: Quality of hospital care for insured
      Medicare patients in influenced both by the patient's race and financial
      characteristics and by the hospital type in which the patient receives care.

PMID- 8151875
TI  - Racial variation in cardiac procedure use and survival following acute myocardial
      infarction in the Department of Veterans Affairs.
AB  - OBJECTIVE: To examine whether blacks admitted to Veterans Affairs Medical Centers
      (VAMCs) with an acute myocardial infarction (AMI) are less likely than whites to
      undergo cardiac catheterization or coronary revascularization procedures and to
      determine the impact of these differences on patient survival. DESIGN: A
      retrospective observational study of inpatient discharge abstracts from the
      Veterans Health Administration (VHA). SETTING: All one hundred fifty-eight acute
      care hospitals in the VHA. PATIENT POPULATION: Male veterans (n = 33,641)
      discharge from VAMCs with an International Classification of Diseases, Ninth
      Revision, Clinical Modification code for AMI from January 1, 1988, to December
      31, 1990. INTERVENTION: None. MAIN OUTCOME MEASURES: The use of cardiac
      catheterization, coronary angioplasty, and/or bypass surgery in the 90 days after
      admission for AMI, and survival at 30 days, 1 year, and 2 years. MAIN RESULTS:
      Adjusting for patient and hospital characteristics, blacks with an AMI were 33%
      less likely than whites to undergo cardiac catheterization, 42% less likely to
      receive coronary angioplasty, and 54% less likely to receive coronary bypass
      surgery. Among patients who underwent catheterization, blacks were also less
      likely than whites to have a subsequent cardiac revascularization procedure.
      Adjusted 30-day survival for blacks was significantly greater than for whites.
      One- and 2-year survival rates after AMI were not significantly different between
      blacks and whites. CONCLUSIONS: In a health care system designed to provide
      equivalent availability of care to all eligible patients, blacks received
      substantially fewer cardiac procedures after AMI than whites. Despite undergoing
      fewer interventional procedures, blacks had better short-term and equivalent
      intermediate survival rates compared with whites.

PMID- 8151876
TI  - Sexually transmitted diseases and other risk factors for cervical dysplasia among
      southwestern Hispanic and non-Hispanic white women.
AB  - OBJECTIVE: To assess risk factors for high-grade cervical dysplasia among
      southwestern Hispanic and non-Hispanic white women. DESIGN: Clinic-based case
      control study. SETTING: University-affiliated gynecology clinics. SUBJECTS: Cases
      were Hispanic and non-Hispanic white women with biopsy-proven high-grade cervical
      dysplasia (n = 201). Controls were Hispanic and non-Hispanic white women from the
      same clinics with normal cervical epithelium (n = 337). METHODS: Study design
      included interviews focused on histories of sexually transmitted diseases, sexual
      behavior, reproductive histories, hygienic practices, contraceptive use,
      cigarette smoking, and diet. Laboratory studies included bacterial and protozoal
      cultures of the cervix; hybridization tests to identify human papillomavirus
      (HPV) genome with commercial (ViraPap and ViraType) and polymerase chain reaction
      based assays; and serum antibody tests for herpes simplex virus, Chlamydia
      trachomatis, syphilis, hepatitis B, and hepatitis C. RESULTS: For both ethnic
      groups combined, after adjustment for ethnicity, age, and sexual behavior, the
      strongest risks for cervical dysplasia were associated with cervical HPV
      infection as identified by ViraPap (odds ratio [OR], 12.8; 95% confidence
      interval [CI], 8.2 to 20.0) or with polymerase chain reaction (OR, 20.8; 95% CI,
      10.8 to 40.2). Other factors associated with dysplasia included cigarette smoking
      at the time of diagnosis (OR, 1.8; 95% CI, 1.2 to 2.8); low income (OR, 2.2; 95%
      CI, 1.2 to 4.0); low educational level (OR, 6.2; 95% CI, 3.4 to 11.1); history of
      any sexually transmitted disease (OR, 1.9; 95% CI, 1.3 to 2.7); and
      seroprevalence of antibodies to hepatitis B (OR, 1.8; 95% CI, 0.9 to 3.5). For
      Hispanic women, HPV 16/18 identified by ViraType was strongly associated with
      cervical dysplasia (OR, 171.0; 95% CI, 22.8 to 1280.5). Antibodies to herpes
      simplex virus type 2 were not associated with dysplasia in Hispanic women but
      were significantly associated with dysplasia among non-Hispanic whites. Risks
      associated with cigarette smoking also varied by ethnic group. CONCLUSIONS: The
      strongest risk factor associated with high-grade cervical dysplasia among clinic
      attendees was HPV infection. Although most of the risk factors we examined showed
      similar associations for dysplasia for both ethnic groups, our data suggest that
      several different risk factors may be relevant to the development of cervical
      dysplasia in Hispanics compared with non-Hispanic whites who attend the same
      clinics.

PMID- 8151877
TI  - Ethical foundations of the Clinton administration's proposed health care system.

PMID- 8151878
TI  - Breast-conservation operations for treatment of cancer of the breast.

PMID- 8151879
TI  - Breast cancer: how to mishandle misconduct.

PMID- 8151880
TI  - Race, class, and the quality of medical care.

PMID- 8151881
TI  - Operative cholangiography.

PMID- 8151882
TI  - Rejuvex for postmenopausal symptoms.

PMID- 8151883
TI  - In Antarctica, the doctor is healer, handyman & wide-eyed tourist.

PMID- 8151884
TI  - Time-tested 'hospital' planes, crews ready for routine or disaster situations.

PMID- 8151886
TI  - From the Health Care Financing Administration and the US Public Health Service.

PMID- 8151885
TI  - Ethicist faults human research subject protection.

PMID- 8151887
TI  - From the Centers for Disease Control and Prevention. Progress toward elimination
      of Haemophilus influenzae type b disease among infants and children--United
      States, 1987-1993.

PMID- 8151888
TI  - From the Centers for Disease Control and Prevention. Examinations of oral cancer-
      United States, 1992.

PMID- 8151889
TI  - From the Centers for Disease Control and Prevention. Injuries associated with
      soccer goalposts--United States, 1979-1993.

PMID- 8151890
TI  - From the Centers for Disease Control and Prevention. Characteristics of women
      receiving family planning services at Title X clinics--United States, 1991.

PMID- 8151891
TI  - Tubal ligation, hysterectomy, and risk of ovarian cancer.

PMID- 8151892
TI  - Tubal ligation, hysterectomy, and risk of ovarian cancer.

PMID- 8151893
TI  - Tubal ligation, hysterectomy, and risk of ovarian cancer.

PMID- 8151894
TI  - Tubal ligation, hysterectomy, and risk of ovarian cancer.

PMID- 8151895
TI  - Mortality among Hispanics.

PMID- 8151896
TI  - Mortality among Hispanics.

PMID- 8151897
TI  - Immunity to measles among health care workers in France.

PMID- 8151898
TI  - Rates of prescribing zidovudine post Concorde Trial.

PMID- 8151899
TI  - Developing the clinical application of genetic diagnosis: the role of NIDDK.

PMID- 8151900
TI  - Prevention of functional impairment by endarterectomy for symptomatic high-grade
      carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial
      Collaborators.
AB  - OBJECTIVE: To determine whether carotid endarterectomy prevents deterioration of
      functional status among patients with transient ischemic attacks or nondisabling
      strokes and ipsilateral carotid stenosis of 70% to 99%. DESIGN: Multicentered
      randomized controlled trial with an average 18-month follow-up. SETTING: Fifty
      clinical centers in North America. PATIENTS: A total of 659 patients presenting
      with recent transient attacks of nondisabling stroke and ipsilateral
      atherosclerotic carotid stenosis of 70% to 99% were included. Patients were
      stable neurologically at the time of entry. No patient was lost to follow-up.
      INTERVENTION: Vascular surgeons and neurosurgeons were prescreened for low
      perioperative complication rates. Patients were randomly allocated to carotid
      endarterectomy plus continuing medical care (n = 328) or medical care alone (n =
      331), including antiplatelet therapy. MAIN OUTCOME MEASURES: All patients were
      assessed by neurologists for the occurrence of stroke and functional status at
      scheduled intervals after entry. RESULTS: In addition to a previously reported
      risk reduction for ipsilateral stroke for patients assigned to carotid
      endarterectomy, there was an absolute risk reduction (and relative risk reduction
      [RRR]) for functional status impairment of 5.6% (RRR, 69%) for vision, 4.6% (RRR,
      87%) for comprehension of language, 8.3% (RRR, 88%) for fluency of speech, 4.3%
      (RRR, 84%) for swallowing, 6.0% (RRR, 53%) for lower-limb function, 9.3% (RRR,
      75%) for upper-limb function, 7.4% (RRR, 60%) for shopping, and 10.5% (RRR, 50%)
      for visiting outside usual residence (P < .05, two-tailed, for all items).
      CONCLUSIONS: Carotid endarterectomy reduced the risk for impairment of function
      among patients with recent symptomatic cerebral ischemia and ipsilateral high
      grade carotid stenosis.

PMID- 8151901
TI  - The appropriateness of performing coronary angiography and coronary artery
      revascularization in a Swedish population.
AB  - OBJECTIVE: To evaluate the appropriateness of performing coronary angiography and
      revascularization in a Swedish population. DESIGN: Prospective population study
      of questionnaires and medical records. SETTING: All the hospitals in southwestern
      Sweden that perform coronary angiography and revascularization. PATIENTS: Random
      sample of 831 patients (with chronic stable angina) on the waiting list for
      coronary angiography or revascularization in southwestern Sweden in September
      1990. MAIN OUTCOME MEASURE: Percentage of patients referred for coronary
      angiography or revascularization for appropriate, uncertain, or inappropriate
      indications. RESULTS: Of the patients referred for angiography, 89% were
      classified as appropriate, 9% as uncertain, and 2% as inappropriate. The
      percentages are similar for patients referred for coronary artery bypass graft
      surgery and for angioplasty (91% and 86%, respectively, classified as
      appropriate). The majority of patients had chest pain rated as Canadian
      Cardiovascular Society classes II through IV (93%), despite maximum anti-ischemic
      therapy in 90% of these patients. CONCLUSIONS: Few patients were referred for
      coronary angiography or revascularization for inappropriate or uncertain
      indications. The percentage of these patients who are from southwestern Sweden is
      similar to the percentage recently reported from New York State.

PMID- 8151902
TI  - Trends in cigarette smoking among US physicians and nurses.
AB  - OBJECTIVE: To determine trends in cigarette smoking prevalence among physicians,
      registered nurses, and licensed practical nurses since 1974. DESIGN: Analyses of
      data on smoking prevalence among persons 20 years of age and older using combined
      National Health Interview Survey data sets from 1974, 1976, and 1977; 1978, 1979,
      and 1980; 1983 and 1985; 1987 and 1988; and 1990 and 1991. MAIN OUTCOME MEASURES:
      Prevalence of cigarette smoking and average annual change in smoking prevalence.
      RESULTS: Based on the data for 1990 and 1991, there were an estimated 18,000
      physicians, 322,000 registered nurses, and 128,000 licensed practical nurses who
      smoked cigarettes in the United States. Compared with 1974, 1976, and 1977, by
      1990 and 1991 cigarette smoking prevalence had declined from 18.8% to 3.3% among
      physicians (average annual decline of 1.15 percentage points); from 31.7% to
      18.3% among registered nurses (average annual decline of 0.88 percentage point);
      and from 37.1% to 27.2% among licensed practical nurses (average annual decline
      of 0.62 percentage point). CONCLUSION: Since 1974, cigarette smoking has declined
      most rapidly among physicians, at an intermediate rate among registered nurses,
      and at a lower rate among licensed practical nurses. Because of their important
      roles as exemplars and health educators, persons in these occupations should not
      smoke.

PMID- 8151903
TI  - Diagnosis and treatment of heart failure based on left ventricular systolic or
      diastolic dysfunction.
AB  - Data from large and small clinical trials reflect major differences in the
      pathophysiology, treatment, and prognosis of left ventricular (LV) systolic and
      diastolic dysfunction. These studies also indicate that medical therapy can
      benefit patients with LV dysfunction regardless of whether or not they are
      symptomatic. Because the descriptive term congestive heart failure does not
      provide for these important distinctions, a new classification of LV dysfunction
      has been developed in which patients with LV dysfunction are categorized on the
      basis of normal or abnormal systolic function. This classification is based on a
      simple assessment of LV function, it is applicable to patients without symptoms,
      and it reflects differences in treatment and prognosis. Those with clinically
      significant LV systolic dysfunction (ie, an LV ejection fraction < 40%) benefit
      from therapy whether or not they have symptoms of heart failure. Those with LV
      dysfunction and a normal LV ejection fraction (ie, diastolic dysfunction) also
      benefit from medical therapy. Annual mortality is higher in those with systolic
      dysfunction than in those with diastolic dysfunction, but within each of these
      categories mortality is higher in those with symptoms than in those without. This
      classification can be useful in the diagnosis and treatment of individual
      patients as well as in epidemiologic surveys designed to assess medical practice
      patterns.

PMID- 8151904
TI  - Thyroid hormone, osteoporosis, and estrogen.

PMID- 8151905
TI  - A national survey of public health officers' interactions with the media.
AB  - OBJECTIVES: To assess the perceptions, practices, and needs of state and local
      health officers with respect to professional interactions with the media. DESIGN:
      A survey of 759 public health officers (56 state and 703 local) on jurisdiction
      demographics, frequency of media interactions, agency process for media contacts,
      provision and need for media training, and character of media relations.
      PARTICIPANTS: Fifty-two state health officers and 568 US local health officers
      responded, for a survey response rate of 82%. RESULTS: Media reporting was
      perceived as accurate 52% to 73% of the time, although reporters were seen as
      needing improved technical and scientific knowledge. Media were used frequently
      as a component of health education. State health jurisdictions were more likely
      than local jurisdictions to have a media protocol and designated media contact,
      to internally review media releases, to interact regularly with media, and to
      provide staff training on media relations. Media interaction time comprised print
      media (63%), television (19%), and ratio (17%). One third of the health officers
      found media relations adversarial, but most held a positive overall view of the
      media. Favorable evaluation of the media was associated with high frequency of
      media contact, high perceived accuracy of reporting, and presence of an
      institutional media protocol. CONCLUSIONS: While health officers evaluated media
      favorably, problem areas were identified where mutual education could improve the
      accuracy and value of media reporting on health issues. Training capacity for
      both professions should be developed to increase the effectiveness of public
      health in media relations.

PMID- 8151906
TI  - [Cross-resistance of Candida albicans to several different families of
      antifungals with ergosterol biosynthesis-inhibiting activity].
AB  - Using 9 strains of Candida albicans mutants resistant to either a triazole
      antifungal vibunazole, an imidazole-antifungal ketoconazole or a morpholine
      antifungal amorolfine, experiments were conducted to see whether cross-resistance
      was developed to any of these 3 different families, as well as to an allylamine
      antifungal terbinafine. All four compounds are known to selectively inhibit
      fungal ergosterol biosynthesis. All the mutant strains were found to be more or
      less resistant to other families of ergosterol biosynthesis inhibitors but not to
      terbinafine.

PMID- 8151907
TI  - [Antimicrobial activities of cefteram against recently clinically detected and
      isolated strains from patients with dental infections].
AB  - To investigate the antibiotic activity of cefteram (CFTM), the minimum inhibitory
      concentrations (MICs) of CFTM and of the control drugs were determined against
      clinically isolated strains received from November 1991 to April 1993 from 19
      dental facilities throughout the country, as well as against clinically isolated
      strains from samples obtained at this center from patients with dental infectious
      diseases, and the following results were obtained. 1. 430 strains were detected
      in 198 cases but identified strains amounted to 425. They are comprised of 204
      strains of oral streptococci (48.0%), 81 strains of Peptostreptococcus spp.
      (19.1%), 10 strains of Bacteroides spp. (2.4%), 23 strains of Prevotella spp.
      (5.4%), and 9 strains of Porphyromonas spp. (2.1%). The ratios of Gram-positive
      bacteria v.s. Gram-negative bacteria were 78.4% and 21.6%, respectively, and the
      Gram-positive bacteria were isolated at higher frequency than Gram-negative
      bacteria. 2. The MIC90's of CFTM against oral streptococci and Peptostreptococcus
      spp. were 0.10 microgram/ml and 0.05 microgram/ml, and year to year increases of
      incidences of resistance against CFTM were not observed. Some strains, however,
      appeared to have obtained resistance to CFTM. 3. Among Bacteroides spp.,
      Prevotella spp., Porphyromonas spp. which used to belong to genus Bacteroides,
      there were some strains resistant to CFTM. As a whole, however, no year to year
      increases in the incidence of CFTM resistance among these strains also. 4. Two
      strains of 6 Staphylococcus aureus subsp. aureus were methicillin-resistant. 5.
      The above observations indicate that CFTM still shows strong antimicrobial
      activity against clinically isolated strains that may be involved in dental
      infections.

PMID- 8151908
TI  - [Antibiotic activities of cefpirome against fresh clinical isolates resistant to
      multiple drugs].
AB  - Using multiple drug-resistant clinical isolates isolated since September 1992,
      minimum inhibitory concentrations (MICs) of cefpirome (CPR) were determined.
      Several control drugs were also used, and these MIC-determinations were made to
      determine the antibiotic activity of CPR. The obtained results are summarized as
      follows: 1. Antibiotic activities of CPR against methicillin-resistant
      Staphylococcus spp., Enterococcus faecalis, and benzylpenicillin-insensitive or
      resistant Streptococcus pneumoniae showed that expanded antibacterial spectrum of
      CPR and its enhanced antibiotic action against Gram-positive bacteria. We suggest
      that among the existing fourth-generation cephem antibiotics, CPR is
      "characteristically strong against Gram-positive bacteria". 2. Strong antibiotic
      activities of CPR were recognized against bacteria of family Enterobacteriaceae
      that were resistant to the third-generation cephems. The strong antibiotic
      activities appeared to be due to CPR's stability and decreased affinity for beta
      lactamase. 3. Antibacterial spectrum of CPR was expanded against non-glucose
      fermented Gram-negative bacilli including Pseudomonas aeruginosa. It appears that
      this expansion of antibacterial spectrum is due to CPR's affinities for a wide
      range of penicillin-binding proteins as well as its improved permeability into
      tissues.

PMID- 8151909
TI  - [beta-lactamase activity in sputum of patients with community-acquired lower
      respiratory tract infections].
AB  - beta-Lactamase production and activities in sputa of patients with community
      acquired lower respiratory tract infections (LRTI) were determined and following
      results were obtained: 1) Suspected causative organisms frequently isolated were
      H. influenzae and Streptococcus pneumoniae. Similar results were previously
      reported. 2) Various beta-lactamase producing indigenous bacteria were detected.
      In many cases these indigenous beta-lactamase producing strains were isolated
      even when suspected causative bacteria were not beta-lactamase producers. 3) beta
      Lactamase activities were detected from 61.5% of the sputa tested. Remaining
      activities of antibiotics added to the sputa were highly correlated with
      detection of beta-lactamases produced by suspectedly causative and indigenous
      strains and with presence of beta-lactamase activities in the sputa.
      Sulbactam/cefoperazone was stable in sputa than other antibiotics tested. 4) We
      concluded that the beta-lactamase produced by indigenous strains can be one of
      the factors of indirect pathogenicity in the community-acquired LRTI.

PMID- 8151910
TI  - [Clinical evaluation of combination therapy of sulbactam/cefoperazone and
      aminoglycoside in respiratory tract infections].
AB  - We compared clinical efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) with
      those of SBT/CPZ combined with aminoglycoside (amikacin (AMK), tobramycin (TOB),
      etc.) in treatment of respiratory tract infections in patients with underlying
      respiratory diseases, with cancer, or with acute exacerbation of chronic
      respiratory infections. Clinical evaluations of monotherapy with SBT/CPZ in a
      total of 30 patients showed excellent results in 5, good results in 17. Clinical
      effects of combined therapy of SBT/CPZ plus different aminoglycosides in a total
      of 33 patients were excellent in 18, good in 5. The efficacy rates (excellent
      plus good) were 73.3% in the monotherapy and 69.7% in the combined therapy. AMK
      was used concomitantly with SBT/CPZ in 16 of 33 patients. Clinical effects of
      SBT/CPZ plus AMK were excellent in 10, good in 3, and the efficacy rate was
      81.3%. Bacteriological effects were evaluable against 11 strains in the
      monotherapy group, and against 17 strains in the combined therapy group. The
      eradication rates were 54.5% in the monotherapy group, and 81.3% in the
      combination therapy group. Diarrhea was observed in a patient who received the
      monotherapy. Abnormal laboratory test results were observed on in 5 patients who
      received the monotherapy, and in 4 patients who received one of the combined
      therapies. All abnormalities disappeared after the completion or discontinuation
      of therapies. We considered SBT/CPZ combined with an aminoglycoside is a useful
      chemotherapy for respiratory tract infections in patients with underlying
      diseases and acute exacerbation of chronic respiratory tract infections.

PMID- 8151911
TI  - [Pharmacokinetic, bacteriological and clinical evaluation of cefditoren pivoxil
      in pediatrics].
AB  - Pharmacokinetic, bacteriological, and clinical studies were performed in
      pediatrics on cefditoren pivoxil (CDTR-PI, ME1207) in granules. 1. Serum
      concentrations and urinary excretions of CDTR after administration of CDTR-PI to
      children (ages between 1 and 10) were investigated. Five cases were administrated
      with CDTR-PI at a dose level of 3 mg/kg 30 minutes after meal. Serum
      concentrations in these cases reached their peaks at 2 hours after administration
      with an average level of 1.23 +/- 0.34 micrograms/ml and diminished to 0.04 +/-
      0.04 micrograms/ml at 8 hours after administration with a half-life of 1.60 +/-
      0.38 hours. Urinary recovery rates of CDTR in the first 8 hours after
      administration of CDTR-PI averaged 14.9 +/- 0.9%. Five cases were administered
      with CDTR-PI at a dose level of 6 mg/kg 30 minutes after meal. Serum
      concentrations with the drug after meal reached their peaks at 1 hour after
      administration with an average level of 2.62 +/- 0.42 micrograms/ml and
      diminished to 0.21 +/- 0.11 micrograms/ml at 8 hours after administration with a
      half-life of 1.58 +/- 0.31 hours. Urinary recovery rates of CDTR in the first 8
      hours after administration of CDTR-PI averaged 17.0 +/- 0.7%. These data also
      showed that serum and urinary concentrations of the drug depended on dose levels.
      2. CDTR-PI was administered to 31 pediatric patients (their ages ranged between 1
      year and 10 years) with various infections, and clinical and bacteriological
      effects and adverse reactions were investigated. Clinical effects were evaluable
      in 24 cases including 2 cases of scarlet fever, 1 case of acute pharyngitis, 12
      cases of acute purulent tonsillitis, 4 cases of acute bronchitis, 5 cases of
      acute pneumonia. Clinical responses were excellent in 16 cases, effective in 8
      cases, with an efficacy rate of 100%. Antimicrobial effects against a total of 16
      strains identified or assumed to be pathogenic bacteria were evaluated. The 16
      strains of bacteria included 4 strains of Staphylococcus aureus, 6 strains of
      Streptococcus pyogenes, 2 strains of beta-Streptococcus, 4 strains of Haemophilus
      influenzae. All the bacteria listed here were judged to have been eradicated
      except 2 strains of H. influenzae (1 was decreased and 1 was unchanged) thus, the
      eradication rate was 87.5%. Two strains of bacteria replaced infection causing
      bacteria. Streptococcus pneumoniae replaced S. pyogenes and S. aureus replaced H.
      influenzae. No adverse side reactions were observed.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8151912
TI  - [A double blind controlled study on S6472 capsules and granules in complicated
      urinary tract infection].
AB  - The efficacy, safety and usefulness of S6472 capsules (cefaclor, long-acting
      preparation) were investigated in non-catheterized patients with complicated
      cystitis using the double blind method with S6472 granules as a control. Each of
      the patients was orally administrated with 375 mg of the drug twice a day for 7
      days, and clinical effectiveness was evaluated according to the Criteria of Drug
      Efficacy of UTI (the Third Edition). The following results were obtained. 1.
      There was no significant bias between the capsule-administrated group (A) and the
      granule-administrated group (B) in background factors. 2. The overall clinical
      efficacy rates were 78.7% in Group A and 80.5% in Group B, which showed no
      significant difference. No significant difference was observed also between
      groups IV and VI in the efficacy for any of the UTI groups. 3. Eradication rates
      in bacteriological response were 85.9% and 86.0% in Group A and B, respectively.
      4. Clinical efficacy rates evaluated according to doctors in charge of patients
      were 78.7% and 74.7% in Group A and B, respectively, showing no significant
      difference between the two groups. 5. The incidences of adverse reactions were
      3.0% in Group A (3 out of 101 cases) and 7.1% in Group B (7 out of 98), thus no
      significant difference was found between the two groups. Abnormal test values in
      laboratory examinations included 5 cases (in 4 among 75 patients) in Group A, but
      were not detected in any of the 76 patients in Group B. No statistically
      significant difference were observed between the two groups, however. 6. No
      significant difference between the two groups was observed in the usefulness
      evaluation including efficacy and safety profiles on an analog scale by the
      doctors in charge of patients. These results indicate that S6472 capsules have
      the same efficacy, safety and usefulness as S6472 granules, suggesting that both
      drugs are equally excellent for non-catheterized patients with complicated
      cystitis.

PMID- 8151913
TI  - [Clinical study on transfer into lung tissue of cefminox].
AB  - Nineteen patients who underwent pulmonary resection due to lung diseases were
      administered with 2 g of cefminox (CMNX) by intravenous drip infusion just before
      surgery. CMNX levels in the serum and lung tissue were determined and
      pharmacokinetic parameters were derived. The obtained results are summarized as
      follows: 1. Pharmacokinetic parameter (K1/K2) derived from serum and lung tissue
      concentrations using deconvolution method was 0.46. 2. CMNX was useful for
      prophylaxis of postoperative infections with lung resection.

PMID- 8151914
TI  - [Studies on aspoxicillin for its transfer to the skin].
AB  - To evaluate the usefulness of aspoxicillin (ASPC) in the field of plastic and
      reconstructive surgery, we examined its transfer to the skin. 1. After
      intravenous drip infusion of ASPC for 1 hour at a dose of 2 g in 13 adults and at
      1 g in 2 children, the mean serum ASPC concentration 1 hour after termination of
      the infusion was 70.46 +/- 28.05 micrograms/ml. The mean concentration in the
      skin tissue 1 hour after infusion in 15 patients was 32.45 +/- 18.47
      micrograms/g. The rate of transfer to the skin 1 hour after infusion in the 15
      patients was 52.9 +/- 29.7%. 2. The ASPC concentrations in skin tissues and the
      rates of its transfer to the skin did not differ significantly between 5 patients
      with facial surgery and 10 with surgery in the trunk or limbs. 3. To prevent
      postoperative infections, ASPC was intravenously drip infused twice daily for 2
      approximately 3 days after operation at a dose of 2 g in adults and 1 g in
      children. No postoperative infection occurred in any patient, suggesting the
      effectiveness of this drug. In addition, no side effects or abnormalities in
      clinical examination values were observed.

PMID- 8151915
TI  - [Cold syndrome (upper airway infection)].

PMID- 8151916
TI  - [Cytomegalovirus pneumonia].

PMID- 8151917
TI  - [Varicella pneumonia].

PMID- 8151918
TI  - [Yersinia pneumonia].

PMID- 8151919
TI  - [Herpesvirus pneumonia].

PMID- 8151920
TI  - [Measles pneumonia].

PMID- 8151921
TI  - [(Pulmonary) candidiasis].

PMID- 8151922
TI  - [Pulmonary cryptococcosis].

PMID- 8151923
TI  - [Coccidioidomycosis].

PMID- 8151924
TI  - [Deep seated mycoses].

PMID- 8151925
TI  - [Sporotrichosis].

PMID- 8151926
TI  - [Trichosporon pneumonia].

PMID- 8151927
TI  - [Pulmonary aspergillosis].

PMID- 8151928
TI  - [Bronchial actinomycosis and pulmonary actinomycosis].

PMID- 8151929
TI  - [Histoplasmosis and progressive disseminated histoplasmosis].

PMID- 8151930
TI  - [Mucormycosis].

PMID- 8151931
TI  - [Pulmonary protozoan diseases].

PMID- 8151932
TI  - [Cryptosporidiosis].

PMID- 8151933
TI  - [Pleuropulmonary amebiasis].

PMID- 8151934
TI  - [Toxoplasmosis].

PMID- 8151935
TI  - [Pneumocystis carinii pneumonia].

PMID- 8151936
TI  - [Gram negative bacterial pneumonia].

PMID- 8151938
TI  - [Leishmaniasis].

PMID- 8151937
TI  - [Malaria].

PMID- 8151939
TI  - [Helminthiasis (pulmonary helminthiasis)].

PMID- 8151940
TI  - [Ascariasis].

PMID- 8151941
TI  - [Sparganosis].

PMID- 8151942
TI  - [Filariasis and dirofilariasis].

PMID- 8151943
TI  - [Paragonimiasis].

PMID- 8151944
TI  - [Pulmonary uncinariasis].

PMID- 8151945
TI  - [Pulmonary strongyloidiasis and pulmonary dirofilariasis].

PMID- 8151946
TI  - [Echinococcosis].

PMID- 8151948
TI  - [Other helminthic diseases].

PMID- 8151947
TI  - [Cysticercosis cellulosae].

PMID- 8151949
TI  - [Gram positive bacterial pneumonia].

PMID- 8151950
TI  - [Mendelson's syndrome (acid aspiration pneumonia)].

PMID- 8151951
TI  - [Wandering pneumonia].

PMID- 8151952
TI  - [Nosocomial pneumonia].

PMID- 8151953
TI  - [Aspiration pneumonia].

PMID- 8151954
TI  - [Exogenous lipoid pneumonia].

PMID- 8151955
TI  - [Organizing pneumonia and BOOP (bronchiolitis obliterans organizing pneumonia)].

PMID- 8151956
TI  - [Chlamydia trachomatis pneumonia and Chlamydia psittaci pneumonia].

PMID- 8151957
TI  - [Primary atypical pneumonia].

PMID- 8151958
TI  - [Mixed pneumonia].

PMID- 8151959
TI  - [Community-acquired pneumonia].

PMID- 8151960
TI  - [New type of scrub typhus (tsutsugamushi disease].

PMID- 8151961
TI  - [Klebsiella pneumoniae pneumonia].

PMID- 8151962
TI  - [Pneumonia in general infection].

PMID- 8151963
TI  - [Intractable pneumonia].

PMID- 8151964
TI  - [Opportunistic infection].

PMID- 8151965
TI  - [Mycoplasma pneumonia].

PMID- 8151966
TI  - [Respiratory infection caused by Rickettsiae (scrub typhus, spotted fever, and Q
      fever)].

PMID- 8151967
TI  - [Pneumonia in the elderly].

PMID- 8151968
TI  - [Small airway disease].

PMID- 8151969
TI  - [Distal acinar emphysema].

PMID- 8151970
TI  - [Round atelectasis].

PMID- 8151971
TI  - [Airway occlusion and airway narrowing].

PMID- 8151972
TI  - [Anaerobic pneumonia].

PMID- 8151973
TI  - [Acute upper airway obstruction].

PMID- 8151974
TI  - [Focal pulmonary emphysema].

PMID- 8151975
TI  - [Bronchiolitis].

PMID- 8151977
TI  - [Congenital lobar overinflation (emphysema)].

PMID- 8151976
TI  - [Centriacinar emphysema].

PMID- 8151978
TI  - [Bullous emphysema].

PMID- 8151979
TI  - [Pulmonary emphysema].

PMID- 8151980
TI  - [Panlobular emphysema].

PMID- 8151981
TI  - [Diffuse panbronchiolitis].

PMID- 8151982
TI  - [Bronchobronchiolitis obliterans].

PMID- 8151983
TI  - [Bacterial respiratory infection].

PMID- 8151984
TI  - [Chronic bronchitis (simple, mucopurulent, obstructive)].

PMID- 8151985
TI  - [Chronic obstructive pulmonary disease].

PMID- 8151986
TI  - [Atelectasis].

PMID- 8151987
TI  - [Chest pain variant asthma].

PMID- 8151988
TI  - [Cough variant asthma].

PMID- 8151989
TI  - [Locked lung syndrome, death from asthma].

PMID- 8151991
TI  - [Allergic bronchopulmonary aspergillosis].

PMID- 8151990
TI  - [Aspirin-induced asthma].

PMID- 8151992
TI  - [Allergic bronchopulmonary candidiasis].

PMID- 8151993
TI  - [Exercise-induced bronchospasm].

PMID- 8151994
TI  - [Bronchial asthma with hypersecretion].

PMID- 8151995
TI  - [Pseudomonas aeruginosa pneumonia].

PMID- 8151996
TI  - [Bronchial asthma].

PMID- 8151997
TI  - [Airway hypersensitivity].

PMID- 8151998
TI  - [Metal induced asthma].

PMID- 8151999
TI  - [Wheat flour asthma (baker's asthma)].

PMID- 8152000
TI  - [Severe exacerbation of asthma and intractable asthma].

PMID- 8152001
TI  - [Bronchial asthma in childhood].

PMID- 8152002
TI  - [Asthmatic bronchitis and acute bronchiolitis].

PMID- 8152003
TI  - [Occupational asthma].

PMID- 8152004
TI  - [Corticosteroid-induced asthma].

PMID- 8152005
TI  - [Adult onset asthma].

PMID- 8152006
TI  - [Non-atopic asthma].

PMID- 8152007
TI  - [Pneumococcal pneumonia].

PMID- 8152008
TI  - [Loffler's syndrome (simple pulmonary eosinophilia)].

PMID- 8152009
TI  - [Hypersensitivity pneumonitis].

PMID- 8152010
TI  - [Infectious pulmonary eosinophilia (parasite and fungus)].

PMID- 8152011
TI  - [Smoking and hypersensitivity pneumonitis].

PMID- 8152012
TI  - [Acute pulmonary eosinophilia].

PMID- 8152013
TI  - [Fulminant type hypersensitivity pneumonitis].

PMID- 8152014
TI  - [Eosinophilic bronchitis].

PMID- 8152015
TI  - [Lung abscess].

PMID- 8152016
TI  - [Eosinophilic lung disease (PIE syndrome)].

PMID- 8152017
TI  - [Hypersensitivity pneumonitis due to thermophilic actinomycetes].

PMID- 8152018
TI  - [Hypersensitivity pneumonitis due to fungi].

PMID- 8152019
TI  - [Asthmatic pulmonary eosinophilia].

PMID- 8152020
TI  - [Idiopathic pulmonary eosinophilia].

PMID- 8152021
TI  - [Tropical pulmonary eosinophilia].

PMID- 8152023
TI  - [Drug-induced pulmonary eosinophilia].

PMID- 8152022
TI  - [Chronic eosinophilic pneumonia and prolonged pulmonary infiltration].

PMID- 8152024
TI  - [Drug-induced pneumonitis].

PMID- 8152025
TI  - [Pulmonary tuberculosis, bronchial tuberculosis, miliary tuberculosis, and
      tuberculoma].

PMID- 8152026
TI  - [Congenital cystic adenomatoid malformation of the lung].

PMID- 8152028
TI  - [Williams-Campbell syndrome].

PMID- 8152027
TI  - [Mounier-Kuhn syndrome, tracheobronchomegaly].

PMID- 8152031
TI  - [Emphysematous bulla and bleb].

PMID- 8152029
TI  - [Bronchiectasis].

PMID- 8152030
TI  - [Bronchogenic cyst].

PMID- 8152032
TI  - [Progressive giant bulla and vanishing lung].

PMID- 8152035
TI  - [Saccular bronchiectasis].

PMID- 8152033
TI  - [Congenital cystic disease of the lung].

PMID- 8152034
TI  - [Pneumonia caused by the 'Streptococcus milleri group'].

PMID- 8152036
TI  - [Cystic disease of the lung].

PMID- 8152037
TI  - [Diffuse bronchiectasis].

PMID- 8152038
TI  - [Pneumonic plague and plague pneumonia].

PMID- 8152039
TI  - [Asbestosis and the other silicate pneumoconiosis].

PMID- 8152040
TI  - [Aluminum lung].

PMID- 8152041
TI  - [Rush dust (Igusa-Sendo) pneumoconiosis].

PMID- 8152042
TI  - [Asbestosis].

PMID- 8152044
TI  - [Metal-related lung disease].

PMID- 8152043
TI  - [Humidifier lung].

PMID- 8152045
TI  - [Graphite pneumoconiosis].

PMID- 8152046
TI  - [Silicosis and Caplan's syndrome].

PMID- 8152047
TI  - [Occupational bronchitis, bronchiolitis, and occupational lung disease].

PMID- 8152049
TI  - [Pneumoconiosis].

PMID- 8152048
TI  - [Pulmonary diseases related to MMMF (man-made mineral fiber) exposure].

PMID- 8152050
TI  - [Inhalation anthrax].

PMID- 8152051
TI  - [Air pollution and respiratory diseases].

PMID- 8152052
TI  - [Talcosis].

PMID- 8152053
TI  - [Coal workers' pneumoconiosis].

PMID- 8152054
TI  - [Pneumoconiosis due to carbonaceous dust].

PMID- 8152055
TI  - [Hard metal disease].

PMID- 8152056
TI  - [Pulmonary diseases due to toxic gases, irritant gases and fumes].

PMID- 8152057
TI  - [Human pulmonary pasteurellosis].

PMID- 8152058
TI  - [Paraquat lung].

PMID- 8152059
TI  - [Byssinosis].

PMID- 8152060
TI  - [Welders' lung].

PMID- 8152061
TI  - [Bronchiolitis obliterans organizing pneumonia (BOOP)].

PMID- 8152062
TI  - [Familial idiopathic pulmonary fibrosis].

PMID- 8152063
TI  - [Interstitial pneumonia and pulmonary fibrosis].

PMID- 8152064
TI  - [Giant cell interstitial pneumonia (GIP)].

PMID- 8152065
TI  - [Idiopathic interstitial pneumonia (IIP), idiopathic pulmonary fibrosis (IPF),
      and Hamman-Rich syndrome].

PMID- 8152066
TI  - [Atypical mycobacteriosis].

PMID- 8152067
TI  - [Granulomatous interstitial pneumonia].

PMID- 8152068
TI  - [Diffuse plasma cell pneumonia].

PMID- 8152069
TI  - [Bronchiolitis obliterans and diffuse alveolar damage (bronchiolitis interstitial
      pneumonia, BIP)].

PMID- 8152070
TI  - [Radiation pneumonitis].

PMID- 8152071
TI  - [Drug-induced interstitial pneumonia].

PMID- 8152072
TI  - [Dietary pulmonary hypertension].

PMID- 8152073
TI  - [Hughes-Stovin syndrome].

PMID- 8152074
TI  - [Bronchial artery aneurysm].

PMID- 8152075
TI  - [Air embolism].

PMID- 8152076
TI  - [Pertussis or whooping cough].

PMID- 8152077
TI  - [Embolic and thrombotic diseases of the lung].

PMID- 8152078
TI  - [Thromboembolic pulmonary hypertension].

PMID- 8152080
TI  - [Fat embolism syndrome].

PMID- 8152079
TI  - [Primary racemose hemangioma of bronchial artery].

PMID- 8152081
TI  - [Pulmonary tumor embolization].

PMID- 8152082
TI  - [Pulmonary vascular abnormalities of developmental origin].

PMID- 8152083
TI  - [Precapillary pulmonary hypertension].

PMID- 8152084
TI  - [Septic pulmonary embolism].

PMID- 8152085
TI  - [Staphylococcal pneumonia and MRSA infection].

PMID- 8152086
TI  - [Pulmonary hypertension].

PMID- 8152087
TI  - [Anomalous pulmonary venous drainage].

PMID- 8152089
TI  - [Pulmonary varix].

PMID- 8152088
TI  - [Pulmonary venous obstruction].

PMID- 8152090
TI  - [Systemic origin of an aberrant artery to the basal segment of the lung].

PMID- 8152091
TI  - [Pulmonary arteriovenous fistulas].

PMID- 8152092
TI  - [Idiopathic dilatation of the pulmonary artery].

PMID- 8152093
TI  - [Pulmonary branch stenosis].

PMID- 8152094
TI  - [Pulmonary sequestration].

PMID- 8152095
TI  - [Pneumonic tularemia].

PMID- 8152096
TI  - [Isolated unilateral absence of the pulmonary artery, isolated unilateral atresia
      of the pulmonary vein].

PMID- 8152098
TI  - [Scimitar syndrome].

PMID- 8152097
TI  - [Chronic recurrent pulmonary embolism].

PMID- 8152099
TI  - [Alveolar capillary leak syndrome].

PMID- 8152100
TI  - [Radiographic diagnosis of interstitial pulmonary edema].

PMID- 8152101
TI  - [High altitude pulmonary edema].

PMID- 8152102
TI  - [Reexpansion pulmonary edema].

PMID- 8152103
TI  - [Hydrostatic pulmonary edema].

PMID- 8152104
TI  - [Branhamella catarrhalis pneumonia].

PMID- 8152105
TI  - [Neurogenic pulmonary edema].

PMID- 8152106
TI  - [Permeability pulmonary edema].

PMID- 8152107
TI  - [Pulmonary edema].

PMID- 8152108
TI  - [Unilateral pulmonary edema].

PMID- 8152109
TI  - [Meigs' syndrome and pseudo Meigs' syndrome].

PMID- 8152110
TI  - [Diffuse malignant mesothelioma].

PMID- 8152112
TI  - [Asbestos pleurisy].

PMID- 8152111
TI  - [Asbestos-related pleural effusion].

PMID- 8152113
TI  - [Viral pleuritis].

PMID- 8152114
TI  - [Pulmonary brucellosis].

PMID- 8152115
TI  - [Pleural effusion caused by trauma].

PMID- 8152117
TI  - [Purulent empyema].

PMID- 8152116
TI  - [Pleural effusion in various diseases].

PMID- 8152118
TI  - [Malignant pleural effusion].

PMID- 8152119
TI  - [Bronchopleural fistula].

PMID- 8152120
TI  - [Pneumothorax].

PMID- 8152121
TI  - [Pleural effusion (transudates and exudates)].

PMID- 8152122
TI  - [Malignant lymphoma of the pleura].

PMID- 8152123
TI  - [Pleural endometriosis].

PMID- 8152124
TI  - [Pleural and subpleural tumors].

PMID- 8152125
TI  - [Fungal diseases of the pleura].

PMID- 8152126
TI  - [Haemophilus pneumonia].

PMID- 8152127
TI  - [Pleural calcification--related to asbestos exposure].

PMID- 8152128
TI  - [Postoperative pleural effusion].

PMID- 8152129
TI  - [Tuberculous pleuritis and tuberculous empyema].

PMID- 8152130
TI  - [Arachnia pneumonia and Nocardia pneumonia].

PMID- 8152131
TI  - [Hemothorax].

PMID- 8152132
TI  - [Catamenial pneumothorax and endometrial pneumothorax].

PMID- 8152134
TI  - [Localized pleural mesothelioma and benign pleural mesothelioma].

PMID- 8152133
TI  - [Anaerobic thoracic empyema].

PMID- 8152135
TI  - [Cholesterol pleuritis].

PMID- 8152136
TI  - [Mixed empyema].

PMID- 8152137
TI  - [Bacterial pleuritis].

PMID- 8152138
TI  - [Pleural effusion due to perforation of the esophagus].

PMID- 8152139
TI  - [Fibrothorax].

PMID- 8152140
TI  - [Legionnaires' disease].

PMID- 8152141
TI  - [Fibrinous pleurisy].

PMID- 8152142
TI  - [Empyema with fistula].

PMID- 8152143
TI  - [Idiopathic eosinophilic pleural effusion].

PMID- 8152144
TI  - [Chylothorax and pseudo-chylothorax].

PMID- 8152145
TI  - [Empyema (primary and secondary empyemas)].

PMID- 8152146
TI  - [Pleural effusion as a complication of radiotherapy].

PMID- 8152147
TI  - [Sterile empyema].

PMID- 8152148
TI  - [Empyema with and without fistula].

PMID- 8152149
TI  - [Interlobar pneumothorax].

PMID- 8152150
TI  - [Interlobar effusion].

PMID- 8152151
TI  - [Streptococcal pneumonia].

PMID- 8152152
TI  - [Influenza pneumonia and parainfluenza pneumonia].

PMID- 8152153
TI  - [Viral bronchitis, bronchiolitis, and pneumonia].

PMID- 8152154
TI  - [Viral respiratory diseases (classification of pathogenic virus)].

PMID- 8152155
TI  - [Application of gene technology to clinical pathology].
AB  - Recently striking progress has been made in molecular biology. Among the newly
      developed techniques, PCR (polymerase chain reaction) is making an epoch in DNA
      diagnosis in the field of clinical pathology and laboratory medicine. In this
      symposium, we discussed the available PCR methods in DNA diagnosis and also the
      future prospect of PCR method as a routine laboratory procedure. First, Dr.
      Kawabata reviewed the PCR technique and analytical procedures of PCR products.
      Next five symposium presented the data on DNA diagnosis for particular diseases
      using the PCR method. Dr. Hasebe presented the HCV genotyping data from the
      patients. Dr. Hirose showed us the difference in accuracy in DNA typing of
      Chlamydia trachomatis antigen between the DNA probe method and PCR method. He
      also introduced the newly developed LCR method. Dr. Kondo reviewed the methods of
      DNA diagnosis for malignant lymphoma. Dr. Yaginuma presented the analyzed data of
      tumor suppressor gene p53 in some gynecological tumors. Dr. Azuma presented a
      case of chronic granulomatosis with a point mutation on the gp91-phox gene which
      had been revealed by RT-PCR. Next Dr. Yagihashi introduced the protocol for DNA
      typing of the HLA class II. Finally, Dr. Tanaka presented the availability of the
      PCR method for the convalescent screening of bone marrow transplantation. We hope
      this symposium is fruitful and motivating for all staffs of laboratory medicine
      and pathology. In closing my remarks, I express our appreciation to all
      symposists as well as Prof. Hisami Ikeda, president of the 27th general meeting
      of the Hokkaido branch, the Society of Clinical Pathology, planned this
      symposium.

PMID- 8152156
TI  - [Diagnosis of type C chronic hepatitis using PCR technology].
AB  - Many studies have suggested that examination of a patient's serum for viral RNA
      by reverse transcriptase-polymerase chain reaction (RT-PCR) is the most sensitive
      and specific serological means of determining chronic HCV infection. Moreover,
      technique to quantify HCV RNA in serum using PCR technology has been developed,
      and diagnosis of HCV genotype by PCR with mixed primers has been used for
      diagnosis of type C hepatitis. Herein, we discuss the laboratory technique and
      significance of various PCR methods. HCV RNA can be detected by amplification
      technique of RT-PCR. Primers in the 5'-noncoding region are frequently used to
      detect HCV RNA, because the RNA sequence in this region is the most conserved. We
      usually perform 30 cycles of amplification with outer primers and another 30
      cycles with inner primers (nested RT-PCR). Using this technique, HCV RNA was
      detected in 96% of anti-HCV-positive chronic hepatitis patients. This PCR
      technique gives us important information for the diagnosis of type C chronic
      hepatitis indicating HCV infection. The competitive PCR technique is usually used
      to quantify HCV RNA. This method is based on complification of the target RNA
      with known amounts of synthetic mutant RNA. The mutant RNA should be amplified by
      the same primers for amplifying target RNA, and should be distinguished from
      target RNA by the size of the amplified DNA product by making a deletion or
      restriction site artificially. Quantifying HCV RNA before interferon therapy is
      useful to predict the effectiveness of the therapy; patients with a large amount
      of HCV RNA tend to have a poor outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152157
TI  - [Genetic diagnoses of Chlamydia trachomatis--DNA probe and PCR method].
AB  - Chlamydial infections such as male urethritis or female cervicitis, although not
      receiving as much attention as the AIDS epidemic, are on the increase around the
      world as sexually-transmitted diseases (STD). A number of diagnostic methods
      i.e., direct fluorescence antibody method and enzyme immunoassay (EIA) methods,
      have been developed for detecting Chlamydia trachomatis (C. trachomatis)
      infection, but they each have a defect in terms of sensitivity or specificity.
      Then, to overcome these disadvantages, the genetic diagnostic method such as DNA
      RNA hybridization (DNA probe) method, PCR method and LCR method have been
      clinically introduced. In in vitro studies, the PCR method has higher sensitivity
      than the EIA method or DNA probe method. All genetic diagnostic methods have
      specificity superior over the EIA method. In clinical studies, the PCR method was
      the most useful for detection of C. trachomatis from various infectious lesions.

PMID- 8152158
TI  - [Analysis of p53 gene in gynecologic tumors].
AB  - The inactivation of the tumor suppressor gene p53 has been demonstrated in a
      variety of human tumors. Herein, we performed a p53 gene analysis of human
      gynecologic tumor cell lines and tumor tissues. In the SK-OV-3 cell line,
      Southern analysis suggested the presence of sequence deletions/rearrangements in
      at least one allele of p53 gene. Transcripts were not detectable by either
      Northern or PCR analysis. Sequencing analysis of the entire coding region
      revealed mutations changing the p53 amino acid composition in all six endometrial
      carcinoma cell lines tested (Ishikawa, Hec1-A, Hec1-B, KLE, RL95-2, and AN-3),
      and four cell lines in ovarian carcinoma cell lines (Caov-3, -4, OVCAR-3, and
      Kuramochi). Of the seven cervical carcinoma cell lines, two (HT-3 and C-33A)
      contained p53 codon changes. We were unable to detect the human papilloma virus
      (HPV) in these two cell lines. By contrast, five HPV-positive cervical carcinoma
      cell lines (HeLa S-3, Caski, SiHa, C-41, and ME-180) contained wild-type p53 gene
      sequences. Examination of loss of heterozygosity (LOH) by PCR revealed that about
      30% of the human ovarian carcinoma tissues has LOH at the locus of p53 gene. We
      suggest that, in the HPV-positive cervical tumors, p53 inactivation occurred via
      the known mechanism of viral E6/cellular p53 protein association, whereas in all
      other tumors (ovarian carcinoma, endometrial carcinoma, HPV-negative cervical
      carcinoma) p53 function was compromised by changes in the amino acid sequence.

PMID- 8152159
TI  - [DNA analysis of cytochrome b positive chronic granulomatous disease (a case
      report)].
AB  - A patient was diagnosed as having chronic granulomatous disease (CGD). This case
      seems to have been transmitted in an X-linked from judging from the family
      history. We had previously suggested that the patient's cytochrome b was normal
      both qualitatively and quantitatively. Thus, we thought that there might be
      mutation in the gp91-phox (one of the two components of cytochrome b) gene
      affecting electron transport but leaving other functions intact. To confirm this
      speculation, we performed DNA analysis. Complementary DNA (cDNA) was obtained
      from messenger RNA (mRNA) derived from peripheral blood lymphocytes. By using
      primers specific for the gp91-phox cDNA, the cDNA was amplified by polymerase
      chain reaction (PCR). The amplified cDNA was then ligated into Blue Script vector
      and transfected into E. coli (JM109) in order to clone the cDNA of gp91-phox.
      Then, the cloned cDNA was sequenced. Sequence analysis showed that the
      nucleotides 1521-1525 were deleted and a new sequence of 8 nucleotides was
      substituted. This mutation converted Glu-Lys-Thr into His-Ile-Trp-Ala. To confirm
      that the mutated allele came from the patient's mother; we performed mismatched
      PCR. PCR using a mutated allele could produce approximately 250 base pair
      products only when the patient's cDNA was used. PCR using a wild type primer
      could produce 250 base pair products only when cDNA from a healthy donor was
      used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152161
TI  - [Hypersensitivity pneumonitis--histopathology of summer-type hypersensitivity
      pneumonitis].
AB  - Summer-type hypersensitivity pneumonitis(SHP) first reported by T. OCHI, et al.
      (1978), as a new type hypersensitivity pneumonitis(HP) with features of
      initiation during summer and anti-Cryptococcus antibody positive sera, has been
      recognized as "a unique disease in Japan", a most common type of HP in Japan, and
      now also known as anti-Trichosporon cutaneum antibody-positive SHP. This report
      was mainly concerned with the histopathology of SHP, thus far diagnosed in our
      hospital. Of the cases in our hospital, 62 consecutive biopsied cases (3 cases of
      open lung biopsy and 59 cases of transbronchial lung biopsy) without steroid
      institution before lung biopsy have been reviewed and revealed granulomatous
      interstitial pneumonitis in the bronchiolo-alveolar region, like various types of
      HP. Alveolitis (61 of 62 cases; 98.4%), sarcoid-like granuloma (50 of 62; 80.6%)
      and Masson's body (36 of 62; 58.1%) are main features, and could be named "triad"
      features. Concerning histopathological findings related with the period of lung
      biopsy after onset of clinical episodes as HP, alveolitis has been present
      regardless of period, and fibrinous exudate present in the early period and not
      in a case at 4 months. Sarcoid-like granuloma and Masson's body have appeared
      firstly at one-month cases. After this period sarcoid-like granuloma have been
      present in nearly all cases, but Masson's body has been not present in 10-month
      case with gradual decrease after 2 months, when all 2-month cases had it. In
      summary, for histopathological diagnosis of HP, the "triad" features and the time
      of lung biopsy done are keys, taking into consideration histopathological
      differential diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152160
TI  - [Clinical application of gene technology to monitor bone marrow transplantation].
AB  - We assessed the origin of peripheral blood cells and bone marrow cells obtained
      from 15 patients after allogeneic bone marrow transplantation (allo BMT) by
      sensitive two-step polymerase chain reaction (PCR) amplification of MCT118, a
      variable number of tandem repeats regions (VNTR), that can be used to detect the
      DNA pattern of a minor cell population of only 1% without using radioisotopes.
      Mixed chimerism(MC) was detected in the haematopoietic cells of 3 patients. Two
      patients developed relapse of leukaemia after the detection of MC and one patient
      died of bone marrow hypoplasia 7 months after BMT. These findings indicate the
      clinical usefulness of this method to monitor patients with MC. Also, we analyzed
      cytokine gene expression in peripheral blood mononuclear cells during the
      development of graft-versus-host disease (GVHD) in patients who underwent allo
      BMT using a semiquantitative reverse-transcriptase polymerase chain reaction (RT
      PCR). The expression of interleukin(IL)-1 beta, IL-6, and tumor necrosis factor
      (TNF)-alpha mRNA was increased during the development of GVHD and the degree of
      this increment depended on the severity of the disease. These findings suggest
      that IL-1 beta, IL-6, and TNF-alpha produced by peripheral blood mononuclear
      cells play an important role in the development of GVHD. Therefore, analysis of
      MC and cytokine mRNA expression using the PCR technique after allogeneic bone
      marrow transplantation provide important information for treatment and monitoring
      of marrow transplant patients.

PMID- 8152162
TI  - [Diagnostic value of bronchoalveolar lavage(BAL)--the comparative study with open
      lung biopsy and BAL].
AB  - Since the introduction of bronchoalveolar lavage (BAL) by Reynolds, et al. in
      1974, this method has gained widespread use as a diagnostic tool in interstitial
      lung diseases. BAL is a safe means of retrieving cells from the distal airway and
      alveoli for cytological, immunocytochemical and biochemical examination, although
      there is still controversy on the significance of the finding and it is a subject
      of current research. We made a comparative study of the results of open lung
      biopsy and BAL analysis. In our study, the results of these two methods showed an
      almost parallel relationship with a few exceptional cases.

PMID- 8152163
TI  - [Multi-center evaluation of Showa ceftizoxime disk susceptibility test to
      discriminate between the strains of methicillin-resistant Staphylococcus aureus
      (MRSA) and those susceptible (MSSA)].
AB  - An increasing prevalence of methicillin-resistant Staphylococcus (S.) aureus
      (MRSA) has a serious therapeutic problem, and accurate methods to detect such
      strains are needed. We studied the antimicrobial susceptibility of S. aureus to
      ceftizoxime, in comparison with those to four other cephems (cefazolin,
      cefoxitin, latamoxef and cefmenoxime), by broth microdilutions and disk
      susceptibility tests, and also evaluated whether the reagents, in replace of
      penicillinase-resistant penicillins (PRPs), could discriminate between the
      strains of MRSA and those susceptible to PRPs (MSSA). A total of 651 clinical
      isolates of S. aureus were collected from six geographically different hospitals.
      All the strains collected were first classified into either MRSA (n = 329) or
      MSSA (n = 322) according to the interpretations of MRSA screening agar, minimum
      inhibitory concentrations (MICs) to oxacillin and methicillin (NCCLS M7-A2), and
      the presence or absence of mecA gene by polymerase chain reaction. In broth
      microdilution tests, the MICs of MRSA to ceftizoxime ranged > or = 64
      micrograms/ml, whereas all the MSSA were at the concentration of < or = 16
      micrograms/ml. The results of Showa disk diffusion tests highly correlated with
      those of MIC determinations. The distribution of inhibitory zone diameters to
      ceftizoxime were clearly divided into two groups; 99.2% (sensitivity) of MRSA had
      inhibitory zones of < or = 20 mm and 98.9% (specificity) of MSSA produced > or =
      21 mm. It was concluded that the Showa ceftizoxime disk susceptibility test was
      useful and enough reliable to screen MRSA isolates in clinical laboratories.

PMID- 8152164
TI  - [The interrelation of serum lysozyme level and cytoplasmic lysozyme level].
AB  - By means of the immunocytochemical method, the level of cytoplasmic lysozyme in
      leukocytes from healthy volunteers (n = 50) and from patients with uremia (n =
      50), leukocytosis (n = 50), various forms of leukemia (n = 36) and
      myelodysplastic syndrome (MDS) (n = 7) were analysed, and compared with that of
      simultaneously assayed serum lysozyme. Both the cytoplasmic and serum levels of
      lysozyme in uremia and leukocytosis were significantly higher than normal
      subjects (p < 0.001). No correlation, however, was found between their
      cytoplasmic and serum levels of lysozyme. Morphological analysis for various
      kinds of leukemia and MDS indicated that myelocytic and monocytic cells became
      highly positive for lysozyme staining with maturation, and that lymphocytes,
      leukemic myeloblasts and monoblasts were negative. The cytoplasmic and serum
      lysozyme levels of leukemias or MDS having a number of lysozyme-positive cells
      were elevated as compared with those of normal individuals. Among them acute
      myelocytic leukemia (FAB M4) revealed an excellent correlation between the
      lysozyme levels in cytoplasm and in serum. The rest whose serum lysozyme level
      tend to be lower than the cytoplasmic one gave poor correlation. Thus, serum
      lysozyme level is not fully reflected by the cytoplasmic level. The dual
      determination of cytoplasmic and serum lysozyme is suggested to be helpful on
      estimating leukemia types, the degree of cellular maturation and total cell mass,
      and might also provide a valuable tool for prediction of prognosis for these
      disorders.

PMID- 8152165
TI  - [Detection of anti-granulocyte antibodies using flow cytometry].
AB  - To detect anti-granulocyte antibodies (AGAs) in the sera of granulocytopenic
      patients is important to study the mechanism of the disease. In this report, we
      studied neutrophil associated immunoglobulin (NAIg) and neutrophil binding
      immunoglobulin (NBIg) in patients' sera using flow cytometry (FCM). We
      investigated the interference of circulating immune complexes (CIC) on measuring
      the NAIg and NBIg. No apparent effect of CIC was observed at concentrations up to
      140 micrograms/ml. NAIg and NBIg were semiquantitated by determining the relative
      fluorescence intensity (RFI) on a flow cytometer and the normal ranges of NAIg
      and NBIg were less than 15 RFI and less than 10 RFI, respectively. Of 100 sera
      from patients with neutropenia, 5 were positive for NBIg and 3 of them were
      positive for granulocyte-specific antibodies. One serum of a patient with benign
      chronic neutropenia showed clear specificity for NA1 alloantigen but the other 4
      AGAs were not specific for NA alloantigen system. Our NAIg, NBIg screening
      procedure, including NA specificity testing of NBIg and detection of reactivity
      with normal lymphocytes using FCM, is simple and useful for measuring and
      studying serological and immunological characteristics of AGAs.

PMID- 8152166
TI  - [Measurement of human thyroid peroxidase autoantibodies by enzyme immunoassay
      using recombinant human TPO].
AB  - An EIA for measuring anti-TPO autoantibodies (rhTPO-EIA) was developed using
      recombinant human TPO expressed in CHO cells and was compared with MC-HA
      generally used in laboratory routine work. rhTPO-EIA showed a satisfactory
      reproducibility in the intra-assay test and did not have an accidental error of
      lots. Almost equal number of healthy females and males were measured for their
      IgG binding to TPO to define a normal range of anti-TPO autoantibodies. After
      setting 20 IU/ml as an upper limit of normal range, sera from patient with
      thyroid disorders were measured for their anti-TPO autoantibodies. Chronic
      thyroiditis and Graves' disease were highly positive, while adenoma, thyroid
      cancer, SLE, and RA were low in their positivity. The positive rate of anti-TPO
      autoantibodies was compatible to those of previous reports in each disorder.
      Seventy-two sera from patients with chronic thyroiditis or Graves' disease were
      measured for their autoantibodies by both rhTPO-EIA and MC-HA and the results
      were compared between both methods. A correlation coefficient was 0.486.
      Following absorption with thyroglobulin, sera were measured again and as the
      results, the correlation coefficient increased to 0.723. Therefore, MC-HA was
      thought to be influenced in the presence of anti-thyroglobulin autoantibodies.
      Since rhTPO-EIA is excellent in quality and not affected by anti-thyroglobulin
      antibodies, it is useful and applicable to clinical diagnosis and observation of
      thyroid disorders.

PMID- 8152167
TI  - [The relationship between Epstein-Barr virus and metastatic lymphoepithelioma in
      the cervical lymph nodes, in comparison with other metastatic carcinomas and
      granulomatous diseases].
AB  - The nasopharyngeal lymphoepithelioma is closely related with Epstein-Barr virus.
      The first clinical manifestation is frequently enlargement of the cervical lymph
      nodes of unknown origin. The histology of the metastatic lymphoepithelioma in the
      lymph nodes sometimes resembles those of other metastatic carcinoma and
      granulomatous diseases. To differentiate the lymphoepithelioma from other
      disorders, we detected Epstein-Barr virus (EBV), using stamp specimens. By
      polymerase chain reaction, all seven lymphoepitheliomas presented amplified EBV
      genomes, while five of the 58 other carcinomas and eight of the 19 granulomatous
      diseases also did. By in situ hybridization, lymphoepitheliomas showed EBV
      genomes which were confined to the tumor cells, though in the other diseases they
      were found in the lymphocytes. Detection of EBV is very useful in making a
      diagnosis of lymphoepitheliomas.

PMID- 8152168
TI  - [Within-day and between-day quality control of white blood cell differential by
      moving-average method].
AB  - Since its first appearance several years ago, automated blood cell analyzers
      capable of calculating white blood cell (WBC)-differential by flowmetric system
      have been widely accepted. Although these analyzers are fast and reliable, any
      other suitable quality control (QC) methods than Levey-Jennings (X) method have
      not been established yet. In this report, we provide evidence that Bull's moving
      average (MA) method is extremely useful for within-day and between-day QC of WBC
      differential assayed with flowmetric NE-7000 system. Monocyte(Mon) content in the
      control blood cells used in X method were varied among each lot, and the
      percentage of neutrophil(Neu) showed a tendency to decrease, while the percentage
      of Mon and basophil(Bas) showed a tendency to increase during storage. On the
      other hand, real-time QC of WBC-differential was enabled by the MA method that
      calculated mean value of each batch consisting of twenty samples. Within-day and
      between-day coefficient of variation (CV%) of WBC-differential controlled by the
      MA method was ranged from 5.0 for Neu to 12.5% for eosinophil(Eos) in patients'
      samples, and from 2.37% for Neu to 11.57% for Mon in healthy adults' samples.
      Therefore, we set up the limit of CV% for QC of WBC -differential by the MA
      method as follows: 10% for Neu, 20% for Lymphocyte, 30% for Mon, 20% for Eos and
      20% for Bas. In addition, we report our experience of one occasion when sudden
      decrease of Mon to below the lower limit of the CV% was indicated by the MA
      method and suitable adjustment was made at once. The change was not detected by X
      method. In conclusion, the MA method is applied to real-time, daily and
      weekly/monthly QC of WBC-differential.

PMID- 8152169
TI  - [Extended aortic arch anastomosis for coarctation of the aorta and interruption
      of the aortic arch in early infancy].
AB  - We performed extended aortic arch anastomosis, which was so called EAA procedure,
      for Coarctation of the Aorta (CoA) with hypoplastic aortic arch (HAA) and
      interruption of the aortic arch (IAA) in 17 infants under three months of age.
      The proximal anastomosis site was extended into ascending aorta in order that we
      could make non-obstructive pathway of systemic flow. During anastomosis, we
      employed mild systemic hypothermia and topical cooling of head and lumber lesion.
      Satisfactory anastomoses were performed without any neurological and renal
      complications except one case. Postoperative Doppler echographic evaluation
      revealed that the mean peak flow velocities at anastomotic site were under 2.0
      m/sec at 1 and 2 years after surgery. We concluded that EAA procedure was useful
      for CoA with HAA and IAA in early infancy.

PMID- 8152170
TI  - [A surgical treatment of ruptured arch aneurysm].
AB  - A 83-year-old woman was admitted to our hospital because of back pain and shock.
      Her chest X-ray and CT scan demonstrated a large arch aneurysm and hemothorax,
      suggesting ruptured aortic arch aneurysm. The ruptured aortic arch aneurysm was
      replaced with a woven Dacron graft under selective cerebral perfusion (SCP). Her
      postoperative course was uneventful without any neurological deficits. For the
      past three years, we have utilized SCP in 12 cases of arch aneurysms. There were
      three early deaths in this series. The cause of death were bleeding in one
      patient and cerebral accident in two patients. The latter two patients had severe
      atheromatous changes in the aortic wall. The SCP technique was a useful method of
      cerebral protection, especially for elderly patient with aortic arch aneurysm.

PMID- 8152171
TI  - [Conduction disturbances after coronary artery bypass grafting with retrograde
      cardioplegia].
AB  - We studied forty-six cases, who had undergone coronary artery bypass grafting
      with retrograde cold blood cardioplegia for myocardial protection, to manifest
      the frequency and causative factors of postoperative conduction disturbances. We
      obtained the following conclusions. 1) Postoperative conduction disturbances
      developed in nineteen cases (41.3%), all of which were right bundle branch
      blocks, but these were usually transient and were not associated with further
      complications in the follow-up period. 2) There were no significant differences
      in many factors, including number of grafts, aortic cross-clamp times, or peak CK
      MB between cases with and without postoperative conduction disturbances.

PMID- 8152172
TI  - [Development and significance of free radical study in cardiovascular surgery].
AB  - Free radicals have just begun to be studied in medical science. There are various
      opinions regarding the initiator of lipid peroxidation, and there will be many
      new discoveries in basic medicine in the future. In cardiovascular surgery, the
      mechanisms of producing free radicals have gradually become clarified for
      ischemic-reperfusion injury of the heart or cardiopulmonary bypass, and effects
      of antioxidants or inhibitors are expected. As to the value of plasma lipid
      peroxide used ordinarily, the absolute value, the cause of lipid peroxidation and
      the value corrected influence of environmental factors, and the effect of lipid
      peroxidation should be used properly to explain the lipid peroxidation. In
      cardiovascular surgery the discoveries in basic medicine should be put to use.
      Discoveries which contribute to the advancement of free radical study may be
      expected, elucidation of the mechanism of lipid peroxidation should be
      determined, and a method for dealing with it should be established.

PMID- 8152173
TI  - [Permanent pacemaker lead insertion for totally occluded subclavian vein].
AB  - We experienced 4 patients with total occlusion of the subclavian vein in whom
      permanent pacemakers were implanted. Occlusion of the subclavian vein was not
      clinically apparent in these 4 patients. The pacing lead was inserted through the
      contralateral subclavian vein in a 65-year-old male. In a 80-year-old male, the
      pacing lead was inserted trough the internal jugular vein because of occlusion of
      both subclavian veins. The pacing lead was passed through the occluded portion of
      the innominate vein in a 84-year-old male. Phlebography-guided venipuncture was
      not difficult in a 79-year-old female whose mid-portion of the subclavian vein
      was occluded. All patients have done well since permanent pacemaker implantation.
      Preoperative phlebography should be performed as it may provide useful
      information concerning pathological alterations in the venous system that might
      hinder smooth implantation of the pacemaker. A review of the literature revealed
      no reports concerning methods in which pacing leads are passed through totally
      occluded portions of the subclavian vein. We here report 4 patients with total
      occlusion of the subclavian vein in whom permanent pacemakers were implanted via
      different venous routes.

PMID- 8152174
TI  - [A case of acute aortic dissection with aortic regurgitation successfully treated
      by postoperative ECMO].
AB  - A case of acute aortic dissection (Stanford Type A) with severe aortic
      regurgitation successfully treated by postoperative ECMO was reported. The
      patient was 41-year-old man in shock condition and was transferred to Kobe
      University Hospital. Chest CT scan and echocardiogram revealed acute aortic
      dissection with severe aortic regurgitation. An emergent operation by Collins'
      method and resuspension of aortic valve were carefully performed. Consequent ECMO
      was necessitated because of postoperative left ventricular and respiratory
      failure. Thereby, ECMO using heparin-coated CBAS-MAXIMA membrane oxygenator,
      centrifugal pump, and tubes was established by arterial cannulation via the
      anastomotic site of the ascending aorta to prevent the obstruction of the aortic
      true lumen by the false lumen which may be enlarged by retrograde perfusion via
      the femoral artery. Left ventricular function and pulmonary function were
      improved after 6 hours and 20 minutes, thus ECMO was successfully weaned without
      any complications.

PMID- 8152175
TI  - [Two case reports of recurrent mediastinitis with chronic mediastinal fistula
      successfully treated with muscle flap re-transposition].
AB  - We experienced two cases of recurrent poststernotomy mediastinitis with chronic
      mediastinal fistula. Both cases had already received muscle flaps for post
      operative mediastinitis. However, chronic mediastinal fistula appeared after nine
      months in the first case, and eleven months in the second case. We removed the
      infected tissue and the predgets, which were used on the ascending aorta. Then
      closed the wound by the muscle flap closure. The chronic fistula were closed, and
      the functional and cosmetic results were excellent.

PMID- 8152176
TI  - [A rare case of total anomalous pulmonary venous connection to the right atrium
      confounding with cor triatrium].
AB  - Three-days-old newborn baby underwent ligation of the ductus arteriosus under the
      diagnosis of TAPVC and PDA with high flow heart failure. Her UCG showed the
      direct connection of common pulmonary venous chamber (CPVC) to the upper and
      medial portion of right atrium. CPVC positioned just above the left atrium but
      does not communicated with the left atrium. These findings characterized this
      anomaly as II A cor triatriatum classified by Lucus-Schumidt. At 5-month-old,
      corrective operation was performed. Both right and left venous chambers joined
      just before the connection to right atrium and drained to right atrium at the
      upper portion of atrial septum. CPVC and left atrium had independent wall.
      Accordingly, operative diagnosis was made as TAPVC (IIb). Intraatrial routing was
      performed using porcine pericardial patch. At 6 months after operation, patient
      is doing well without the sign of venous obstruction. This type of TAPVC is rare
      and may confound with cor triatriatum. Our case may suggest the pathological
      mechanism of cor triatriatum and that at least some of cor triatriatum may be
      identical with TAPVC.

PMID- 8152177
TI  - [A case report of aneurysm of the diverticulum of the ductus arteriosus in the
      elderly].
AB  - A 82-year-old female was admitted to our department with complaint of hoarseness.
      Retrograde aortogram revealed an aneurysm arising from distal aortic arch. The
      aorta including the aneurysm was resected and replaced with woven Dacron graft
      under partial cardiopulmonary bypass. An Aneurysm of the diverticulum of the
      ductus arteriosus is rare in adult and because of its high fatality it should be
      resected.

PMID- 8152178
TI  - [A case report of surgical treatment for coronary aneurysm following repeated
      PTCA].
AB  - A 53-year-old man who developed coronary artery aneurysm following repeated
      percutaneous transluminal coronary angioplasty (PTCA) was reported. At the first
      coronary angiography, the severity of coronary stenosis was 95% at areas #6 and
      #7. The first PTCA provided sufficient coronary dilatation, but 3 months later,
      PTCA was needed again because of the recurrence of stenosis. This second PTCA
      provided sufficient dilatation, but the coronary dissection remained. Eight
      months after the second PTCA, the patient suffered from recurrent angina. The
      repeated coronary angiography showed 95% stenosis of the original lesion and
      coronary aneurysm formation (4 mm in diameter) at the area of dissection which
      developed at the former PTCA site. Therefore, coronary artery bypass surgery with
      left internal thoracic artery to area #8 was performed.

PMID- 8152179
TI  - [Superior vena cava-right atrial appendage direct anastomosis for repair of
      partial anomalous pulmonary venous connection to superior vena cava].
AB  - Successful repair was performed for a 7-year-old male with a diagnosis of partial
      anomalous pulmonary venous connection (PAPVC) to superior vena cava (SVC) and
      superior sinus venosus atrial septal defect (ASD). The SVC was divided above the
      orifice of the anomalous pulmonary vein and the cephalad end of the SVC was
      anastomosed directly to the right atrial appendage. A patch was used to divert
      pulmonary venous flow from the orifice of the SVC through superior sinus venosus
      ASD into the left atrium. Postoperative course was uneventful with normal sinus
      rhythm. There was no evidence of vena caval or pulmonary venous obstruction. At 3
      month after surgery, sinus node function was confirmed to be normal by
      electrophysiological study. This is useful alternative method for repair of PAPVC
      to high or middle SVC.

PMID- 8152180
TI  - [An operative case of aortic regurgitation due to quadricuspid valve].
AB  - A case of quadricuspid aortic valve is described. A 43-year-old man admitted
      because of chest oppression on exercise. He had a ejection systolic murmur and
      decrescendo diastolic murmur. Electrocardiogram revealed severe left ventricular
      hypertrophy. Echocardiogram showed dilated left ventricle and supernumerary cusp
      between the right and left coronary cusp. Aortogram revealed quadricuspid aortic
      valve with grade 4 aortic regurgitation. At operation, quadricuspid aortic valve
      in which supernumerary cusp between right and left coronary cusp was smaller was
      found. Four cusps were excised and replaced with 23 mm Medronic-Hall prosthesis.
      His postoperative course was uneventful. Quadricuspid aortic valve has been
      extremely rare. Twenty operative cases has been reported. The clinical feature
      was presented.

PMID- 8152181
TI  - [Coronary artery spasm after mitral valve replacement: a case report].
AB  - A 50-year-old female with a malfunctioning bioprosthetic mitral valve which was
      implanted 7 years earlier underwent reoperation. She had no history of angina
      pectoris. Calcium channel blockers and nitrates had not been taken by the
      patient. Coronary arteriograms were normal. About 2 hours after the reoperation,
      EKG monitor showed abrupt ST segment elevation which was immediately followed by
      ventricular tachycardias and fibrillations. This life threatening circulatory
      collapse recurred until a drip infusion of diltiazem was started. Maximum CPK-MB
      was 145 IU/l. Postoperative coronary arteriography, which was performed after 12
      hours of withhold of diltiazem, showed a spasm in the proximal segment of the
      right coronary artery. Coronary artery spasm should be considered among the
      causes of abrupt and unexpected circulatory collapse after open heart surgery
      even in the absence of coronary artery disease.

PMID- 8152182
TI  - [A case of micro-metastatic lung adenocarcinoma into adenoma of the thyroid].
AB  - In a case of 46-year-old woman, small nodules appeared in the anterior neck which
      was diagnosed as follicular adenoma of the left lower lobe of the thyroid. Four
      months before, she experienced resection of the lung and three courses
      chemotherapy of MVP for stage IIIb well-differentiated lung adenocarcinoma.
      Pathologically, micro-metastatic lung adenocarcinoma was found in the adenoma. It
      is very rare occurrence for lung carcinoma to metastasize into adenoma of the
      thyroid. But when tumors of the anterior neck are found in a patient of lung
      carcinoma, thyroid tumor must be considered for differential diagnosis.

PMID- 8152183
TI  - [A case of mediastinal cystic lymphangioma in childhood].
AB  - We report a case of lymphangioma, which was widely extended from anterior to
      posterior mediastinum. The patient was an asymptomatic six-year-old male with a
      right upper mediastinal mass on chest roentgenograms. Computed tomogram showed a
      large anterior mediastinal mass, which extended to upper and posterior
      mediastinum, involving thymus, superior vena cava and innominate vein. Through
      midline sternotomy, the tumor was visualized and was invading the thymus,
      bilateral phrenic nerves, SVC and innominate veins. The tumor was also found to
      extend to the right side of the trachea and vertebra along the azygos vein. The
      tumor was resected successfully with the preservation of bilateral phrenic
      nerves. Macro-and microscopic examination revealed polycystic tumor with
      endothelialized inner spaces. Some cysts contained smooth muscle in their walls.
      Supportive structures contained variable amounts of fat and connective tissue.
      The patient weaned from mechanical respiratory support on the first post
      operative day, although his diaphragms elevated slightly with poor movement.
      Phrenic nerve palsy was suspected, but the position and the movement of
      diaphragms improved four months after the operation. The patient has been well
      and free from tumor recurrence for four years since the operation.

PMID- 8152184
TI  - [A case of mediastinal neurilemmoma originating from the intrathoracic vagal
      nerve].
AB  - A case of neurilemmoma originating from the intrathoracic vagal nerve was
      reported. An asymptomatic 51-year-old man was admitted because of a mass shadow
      on chest roentgenograms. Under the possible diagnosis of benign bronchogenic
      cyst, right thoracotomy was carried out. An encapsulated solid tumor originating
      from the right vagal nerve was found in the site distal to the branching point of
      recurrent nerve. The tumor was removed by transection of the vagal nerve.
      Postoperative clinical course was uneventful except the transient sinus
      tachycardia. The pathological diagnosis was neurilemmoma. Mediastinal
      neurilemmoma originating from the vagal nerve is rare. To our knowledge, only 29
      cases are reported in the Japanese literatures.

PMID- 8152185
TI  - [A case of lung cancer combined with ocular myopathy and idiopathic
      thrombocytopenic purpura which was presumed to be caused by heart
      catheterization].
AB  - A 61-year-old patient was admitted to our hospital because of a chest abnormal
      shadow. He was suffered from ocular myopathy for more than 4 years. A lab data on
      the admission showed only a slight thrombocytopenia. After the unilateral
      pulmonary arterial occlusion test for the preoperative evaluation of thoracotomy,
      the hemorrhagic tendency was appeared. A detailed examination proved idiopathic
      thrombocytopenic purpura which was presumed to be caused by the heart
      catheterization. We employed high-dose intravenous gamma-globulin infusion and
      concentrated platelet transfusion for 5 days for preventing hemorrhagic
      complications during the thoracotomy. The partial resection was undergone for the
      left upper lobe tumor, which was proved as large cell carcinoma. The
      postoperative hemorrhage was well controlled. We conclude that the high-dose
      intravenous gamma-globulin infusion and/or concentrated platelets transfusion
      should be positively employed for the patients with even slight thrombocytopenic
      purpura.

PMID- 8152186
TI  - [Experience with surgery for metachronous double cancer originated from thymus
      and lung].
AB  - A case with thymic cancer who developed pulmonary cancer ten years after the
      initial surgery was reported. A 50-year-old man was admitted to our hospital due
      to SVC syndrome. Chest X-ray examinations including venogram showed a mass lesion
      at the superior mediastinum. The patient underwent surgical removal and
      reconstruction of SVC, followed by radio-chemotherapy. The histologic diagnosis
      was thymic squamous cell carcinoma. He was admitted to our hospital again ten
      years after the initial surgery under the diagnosis of pneumonia. Bronchoscopic
      examination revealed nodular lesions at the right upper lobe bronchus and lower
      lobe bronchus, those lesions were diagnosed with squamous cell carcinomas
      cytologically. Right pneumonectomy was performed and the diagnosis was confirmed
      pathologically. Postoperative course was uneventful as of 10 months after the
      operation. It was concluded that this case showed metachronous double cancer of
      the thymus and the lung, as well as synchronous multiple bronchogenic carcinomas,
      which, to our knowledge, has never been reported yet.

PMID- 8152187
TI  - [Chronic empyema associated with large cell carcinoma of lung: case report with
      review of the literature].
AB  - A 71-year-old female was seen with a complaint of chest pain and cough, and a
      history of tuberculous pleurisy and artificial pneumothorax 40 years ago. The
      diagnosis of empyema with carcinoma was made by chest X-ray and CT scans. The
      examination of lung function showed a restrictive disorder. The value of the
      predicted postoperative FEV1 0.75 l encouraged to perform operation. A left
      pleuropneumonectomy and combined resections of the invasive portion of the
      pericardium and left atrium was performed. Histological examination revealed
      large cell carcinoma of lung (pT 4 N 1 M 0). The literatures are reviewed
      concerning the thoracic malignant tumor arising in chronic empyema cavity on
      Japanese cases.

PMID- 8152188
TI  - [Review of the past year--"cornea"].

PMID- 8152189
TI  - [New developments in 1991 in the field of the eyelids].
AB  - The publications of the year 1991 dealing with new developments in the field of
      lids have been reviewed. New methods of reconstruction of the upper and lower eye
      lid are presented. Chondroplast is a substitute for the tarsal plate which is
      preserved in a new way and is available in an unlimited amount. A four snip
      procedure for the correction of lower lid entropion is presented. A new technique
      of ectropion correction which allows great flexibility in the extent of the
      approximation of the lower lid to the globe is available. New simplified
      variations of the surgical treatment of Graves' disease provide a predictable
      height and contour of the eye lid as well as improved cosmetic results.
      Alternatively to Botulinum toxin Doxorubicin was injected as a treatment for
      benign essential blepharospasm and hemifacial spasm in an experimental study.

PMID- 8152190
TI  - [Effect of diffractive multi-focal lenses on contrast vision, glare sensitivity
      and color vision].
AB  - BACKGROUND: Due to theoretical considerations an increase in the depth of field
      of the diffractive IOL may be combined with a reduction in contrast sensitivity,
      glare sensitivity and colour perception. PATIENTS AND METHODS: A comparative
      analysis of both eyes was performed in ten patients with a diffractive multifocal
      IOL (3M 815LE) in one eye and a monofocal IOL in the other eye. Contrast
      sensitivity was examined by computer generated sine wave gratings of 6 different
      spatial frequencies; visual acuity with glare and glare sensitivity were
      determined under 7 different levels of field luminance; colour vision was
      examined using the Farnsworth-Munsell-100-Hue-test. RESULTS: Contrast sensitivity
      of the diffractive lens was reduced for intermediate spatial frequencies, but not
      for low and high frequencies. Visual acuity with glare was only reduced at
      maximum field luminance; no differences were found in glare sensitivity and
      colour perception between monofocal and multifocal. CONCLUSION: Altogether, the
      diffractive lens did not show a dramatic reduction in the examined visual
      functions compared with the monofocal IOL.

PMID- 8152191
TI  - [Cryotherapy in treatment of neovascular glaucoma with closed chamber angle].
AB  - BACKGROUND: The purpose of this study was to compare the clinical results of two
      cryosurgical methods in the treatment of neovascular glaucomas. PATIENT AND
      METHODS: In 43 eyes with acute neovascular glaucomas, cryosurgery was carried
      out. In 12 eyes, cyclocryocoagulation was performed as a single operation,
      whereas in 31 eyes transscleral panretinal cryocoagulation was combined with
      cyclocryocoagulation in one surgical session. The authors assess the effect of
      these two cryosurgical methods on the intraocular pressure, pain of the eye,
      visual acuity and neovascularization of the iris. RESULTS: The results of
      cyclocryocoagulation versus transscleral panretinal cryocoagulation in
      combination with cyclocryocoagulation were the achievement of an intraocular
      pressure up to 26 mmHg within 6 weeks after the operation: 5 (42%) v. 25 (81%),
      failure in reduction of the intraocular pressure: 4 (33%) v. 2 (6%), achievement
      of an only transient effect of reduction of the intraocular pressure: 3 (38%) (n
      = 8) v. 3 (14%) (n = 22). Regression of pain within 5 days postoperatively: 55%
      v. 100%. In five of six eyes, treated by application of the combined operation,
      the maintained visual acuity was 6/24-2/60 for a period of 6 months up to 1 year
      postoperatively. CONCLUSION: The method of transscleral panretinal
      cryocoagulation in combination with cyclocryocoagulation shows better results
      than the performance of cyclocryocoagulation only.

PMID- 8152192
TI  - [Digital data collection and analysis in clinical electrophysiology. A PC program
      for electrophysiology].
AB  - BACKGROUND: The number of data acquired in electrophysiology and the need for
      immediate analysis and interpretation justified the use of computerized signal
      acquisition and -analysis. Since such techniques are well known and established
      in computerized perimetry, the user of EOG, ERG, and VEP will profit from such an
      approach. METHOD: A computer program for signal acquisition and -analysis of
      clinical electrophysiology is described. The software is written in BASIC for IBM
      compatible PC/XT/AT computers. The program supports all electrophysiological
      examinations (EOG, ERG, VEP). It contains a subroutine for automated EOG
      recording and -analysis, allows measurements of amplitude and latency of
      standardized Ganzfeld-ERG and pattern-ERG. Options for recording and analysis of
      further stimuli are prepared. The possibility of determination of area under the
      curve is implemented. In the VEP subroutine evaluation of amplitude, latency,
      area under the curve, and Fast-Fourier-Transformation--necessary for steady-state
      VEP--is installed. CONCLUSION: The program demonstrates that with the now
      available low cost Personal Computer technology it is possible to build up
      individual software systems for clinical electrophysiology supporting and
      optimizing all recording, analysing, and administrative procedures.

PMID- 8152193
TI  - [Self-inflicted injuries of the eye: differential diagnosis of self-inflicted
      lacerating corneal injury].
AB  - BACKGROUND: Recognising self-inflicted injuries is the prerequisite to initiate
      specific, psychiatric, therapy of the often underlying psychiatric disorders. The
      differential diagnosis of Oedipism, self-inflicted ocular injury, includes
      Munchausen's-syndrome, neuroses and schizophrenic psychoses. PATIENT: We present
      a patient in whom a self-inflicted corneal lancinating injury was the first sign
      of an acute relapse of his previously known paranoid-hallucinating schizophrenia,
      requiring immediate treatment. CONCLUSION: In patients with unexplained ocular
      disease self-inflicted ocular injury needs to be taken into consideration as the
      treatment of such patients requires close cooperation of Ophthalmologists and
      Psychiatrists.

PMID- 8152194
TI  - [Tyndallometry in monitoring therapy of sympathetic ophthalmia].
AB  - BACKGROUND: The Laser Flare-Cell Meter allows noninvasive quantitative
      measurement of aqueous flare in human eyes. In this study we analysed changes of
      aqueous flare in eyes with sympathetic ophthalmia under immunosuppressive
      treatment. PATIENTS AND METHOD: Two men (54- and 59-year-old) with sympathetic
      ophthalmia (histological examination of the enucleated eyes confirmed the
      clinical diagnosis) were examined regularly with the Laser Flare-Cell Meter
      (Kowa). According to the flare values the dose of immunosuppressive treatment
      with cyclosporin A and prednisolone was gradually titrated. RESULTS: Under
      immunosuppressive treatment flare values of patient 1 normalized within 21
      months. The dose of immunosuppressive treatment was carefully reduced according
      to flare values. Patient 2 showed very high flare values before treatment, which
      decreased to flare values of 20 flare counts/ms within 5 months of treatment with
      cyclosporin A and prednisolone. Both patients stopped immunosuppressive treatment
      because of systemic side-effects. Thereafter flare values increased acutely and a
      recurrence of sympathetic ophthalmia was observed in both patients. Under renewed
      immunosuppressive treatment aqueous flare values decreased again. CONCLUSION:
      Measurement of aqueous flare with the LFCM appears to be an effective tool for
      follow-up examinations, and especially for titrating of immunosuppressive
      treatment in eyes with manifest sympathetic ophthalmia.

PMID- 8152195
TI  - [Limitation of lens power in automobile drivers].
AB  - High plus lenses may cause defects in the peripheral visual field. Simple full
      vision lenses or lenticular lenses without a masked transition zone caused an
      absolute ring scotoma in the mid-periphery. Patients who were glasses of this
      type cannot see well enough to drive safely. Although modern edge finishes with
      masking of the transition zone reduce this problem, visual disturbances in the
      periphery of the lenses cannot be completely eliminated. A recommendation
      recently issued by the German Ophthalmological Society concerning maximum lens
      powers for motorists is aimed at preventing visual field defects of this type.

PMID- 8152196
TI  - [Ophthalmology in Leipzig and Dresden 100 years ago].
AB  - BACKGROUND: Based on a rich ophthalmologic tradition in Saxony--for example Georg
      Bartisch (1536-1606) and his "ophthalmoduleia" furthermore the anatomist and
      surgeon of the university of Leipzig Justus Gottfried Guenz (1714-1754), working
      about the staphyloma and criticizing the notorious oculist John Taylor (1703
      1772)--the situation at Dresden and Leipzig is described. The development was
      dynamical, scientifical and in the end independent of surgical specialty.
      Physiology (Purkinje, Helmholtz), obstetric (Crede) and other medical specialties
      had a great influence on the ophthalmology too. MATERIAL AND METHODS: The
      investigation predominantly is determined by the "Staatshandbuch fur das
      Konigreich Sachsen" and by the also important address-books of Dresden and
      Leipzig. In this material are to find the number of ophthalmologists, of clinics
      and practices as well as the kinds of work. RESULTS: The ophthalmology in Saxony
      100 years ago, especially in the university of Leipzig and in the capital of this
      country, Dresden, may be mirror of the development in whole Germany. As well in
      the academic field as in the ophthalmology the specialty was very spreaded and
      accepted. CONCLUSIONS: In the focus of the ophthalmological picture the extent
      and the level or the quality of this medical specialty stands. We can say, that
      the oculists at that time are versed in concerning the operative and conservative
      therapy. The social welfare played a part in the supply of the blind and in the
      prescription of glasses. With reference to the chairs and many personalities
      Saxony was a centre of ophthalmology in Germany.

PMID- 8152197
TI  - [Refraction in childhood as a risk factor for the development of amblyopia and/or
      strabismus. Recording a round table discussion at the 89th Congress of the German
      Society of Ophthalmology 25 September 1991 in Leipzig].
AB  - The members of the panel refer to the recent literature. As has been shown by
      several groups of authors (Atkinson et al., Abrahamsson et al., Ingram et al.)
      hypermetropia of 3 diopters or more as well as astigmatism of 1 or more dpt at
      the age of 12 months, especially oblique astigmatism, increase the rate of
      amblyopia/strabism until the age of 4 years. The risk rises too, if the
      refractive error deteriorates. The authors conclude that the prescription of
      glasses in non-squinters should be based on these new findings.

PMID- 8152198
TI  - [Meeting of the Society of Bavarian Ophthalmologists. Munich, 5-6 June 1993.
      Abstracts].

PMID- 8152199
TI  - [EEG changes in type I and type II lissencephaly].
AB  - Lissencephaly syndromes are rare disturbances of the neuronal migration with
      agyria and/or pachygyria. Typical patterns in the EEG of 5 children with
      lissencephaly are presented. Rhythmic alpha- or beta-waves with high amplitudes
      of diffuse or fronto-precentral localisation are characteristic in type I
      lissencephaly. In type II lissencephaly initially theta- or delta-waves of
      somewhat lower amplitude are observed. Sharp and slow wave-complexes of very high
      amplitude are found more often in type I lissencephaly. They seem to correlate
      with the severity of the brain malformation and the epilepsy. In both types of
      lissencephaly the spatial organisation of the background activity and the sleep
      wake differentiation are absent. The EEG of most type I lissencephalies show no
      reactivity to intravenous benzodiazepines. With increasing age the frequency of
      the background activity and of the high amplitude rhythmic waves decrease in type
      I and increase in type II lissencephaly. A complete dedifferentiation of the EEG
      tracings has been observed in the course of type I lissencephaly. Lissencephaly
      is diagnosed by imaging techniques. However, with a high probability
      lissencephaly can be suspected already by its EEG.

PMID- 8152200
TI  - [Effectiveness and complications of percutaneous central venous catheters in
      neonatal intensive care].
AB  - Low birth weight babies and sick full-term babies, who require total parenteral
      nutrition and repeated intravenous applications of drugs, which irritate
      peripheral veins, very often need a reliable central venous catheter. The aim of
      our paper was to study prospectively the efficiency and the complications of
      peripheral percutaneous Silastic-catheters. Over a period of 9 month we inserted
      114 central venous catheters via peripheral veins in 111 premature babies and
      sick full-term infants at our neonatal intensive care unit. The mean duration of
      use was 13.7 days, the catheter-induced septicaemia-rate was 3.5%. We never saw
      serious complications of a central venous catheter, the most common complication
      was an intravasal central obstruction, but we found no relation between the
      occurrence-risk of complications, the duration of use and the infusion flow rate.

PMID- 8152201
TI  - [Clinical applications of cytokines in pediatrics].
AB  - Cytokines are decisive for the regulation of the immune system as well as the
      renewal and maturation of the haematopoietic cells. The most important groups of
      substances, several of which are already produced by gentechnology, are the
      interferons, the interleukins and the haematopoietic growth factors. The main
      indications for the application of alpha-(less often beta-)Interferon in children
      are the juvenile larynx papillomatosis, chronic hepatitis B, viral encephalitis,
      and also chronic myeloic leukemia, extended haemangiomas, recurrent Langerhans
      cell histiocytosis and nasopharynx carcinomas. gamma-Interferon is administered
      successfully for chronic granulomatous disease and has recorded positive effects
      in therapy resistant rheumatoid arthritis, in kidney cell carcinoma and in
      osteopetrosis. G-CSF, GM-CSF and Interleukin 3 are the most effective
      haematopoietic growth factors currently in use. Through G-CSF congenital
      agranulocytosis (Kostmann syndrome) has become a treatable disease. Other proven
      applications are in the reduction of aplastic phases after chemotherapy and in
      critical situations of primary bone marrow failure as well as myelodysplastic
      syndromes, for prevention of transplant rejections after bone marrow
      transplantation and for mobilisation of stem cells into peripheral blood before
      apheresis. Erythropoietin is established in the treatment of chronic renal
      anaemia and is currently used in the treatment of anaemia in preterm infants.
      Finally, Interleukin 2 is also used for adoptive immunotherapy in children with
      minimal residual tumors. The future will show us, whether the spectrum of
      indications will expand and whether a definite benefit for sick children will
      result from a wider application of these substances. As long as the cost/benefit
      ratio for certain indications is not clear, the use of these drugs should be
      tested in prospective studies.

PMID- 8152202
TI  - [Effectiveness and tolerance of cefixime in bacterial urinary tract infections in
      patients with myelomeningocele].
AB  - 28 myelomeningocele patients (aged 2-30 years) with clinical symptoms of acute
      UTI participated in this open uncontrolled clinical trial at the Orthopedic
      University Hospital of Heidelberg (Dir.: Prof. Dr. H. Cotta). 4 patients were
      treated with 200 mg cefixime tablets bid, 24 patients received 4 mg/kg body
      weight cefixime suspension bid, according to age and weight of the patients. The
      duration of treatment was 6-10 days. Clinical and microbiological examinations
      were carried out before therapy as well as 1 day and 5 to 9 days after the end of
      treatment. The data of 25 patients could be evaluated for bacteriological and
      clinical efficacy. 5-9 days after treatment in 22 patients (88%) complete
      recovery was stated. In 3 patients a reinfection occurred. In 24 patients (96%)
      the baseline pathogens were eliminated under cefixime therapy. 5-9 days after the
      end of treatment in 3 patients reinfection was observed. Clinical side effects
      could be detected in 1 patient (vomiting). These results indicate that the oral
      cephalosporin cefixime is efficient and well tolerated in complicated UTI of
      myelomeningocele patients.

PMID- 8152203
TI  - [Effectiveness and tolerance of cefixime in comparison with penicillin V in
      bacterial pharyngitis and tonsillitis in children. Cefixime Study Group].
AB  - 154 children aged 2 to 12 years with clinical diagnosis of bacterial pharyngitis
      and/or tonsillitis and--in most of the patients--a positive enzyme immunoassay
      for group A beta-hemolytic streptococci before therapy were enrolled in this open
      controlled randomized and multicenter trial. The children received either 8 mg/kg
      bodyweight cefixime once daily or 20,000 I.E. pencillin V/kg bodyweight t.i.d.
      Clinical evaluation and microbiological tests were carried out before treatment
      and 1-5 days after end of the treatment. 3-4 weeks after end of the treatment the
      rate of relapses was evaluated. The data of 149 children could be evaluated for
      clinical efficacy. In the cefixime group 93.3% of the children were cured and
      6.7% improved compared to 89.2% and 10.8%, respectively, in the penicillin V
      group. Complete microbiological data were obtained from 136 patients. The
      eradication rate was 82.7% in the cefixime group and 77% in the group of patients
      treated with penicillin V. At follow up relapses were seen in 7 of the cefixime
      treated patients and in 6 of those receiving penicillin V. Mild side effects were
      reported by 4 patients in the cefixime group and by 3 children treated with
      penicillin V (1 drop out each). These results show that cefixime once daily is at
      least as effective as penicillin V t.i.d. in pharyngitis and tonsillitis in
      children. Both compounds are well tolerated.

PMID- 8152204
TI  - [Indirect molecular-genetic family study and prenatal diagnosis of infantile
      spinal muscular atrophy].
AB  - Spinal muscular atrophy is one of the most common severe inherited diseases in
      childhood and especially the acute form of type I (Werdnig-Hoffmann) results in
      early death. Recently, all three types of childhood-onset SMA have been mapped to
      chromosome 5. Since then heterozygote detection in siblings and prenatal
      diagnosis of SMA type I is possible by indirect genetic analysis. As the gene and
      the mutation responsible for the disease have not yet been cloned, DNA analysis
      results in a risk figure which depends on the informativity and recombination
      frequency of the flanking markers studied.

PMID- 8152205
TI  - High-molecular-mass or macromolecular alkaline phosphatase in sera of children
      with solid tumors.
AB  - High-molecular-mass alkaline phosphatase (H-Mr AP) was detected in sera from
      children with solid tumors without liver metastases. H-Mr AP activities were
      determined by a liquid chromatographic and an electrophoretic method. In 5 out of
      10 cases with solid tumors--Ewing sarcoma (n = 2), neuroblastoma (n = 2), and
      rhabdoid tumor (n = 1)--H-Mr AP activities ranged from 3.1-40.4 U/L and 3.1-16%
      of total serum AP activity. In sera of patients with leukemia (n = 18) H-Mr AP
      was not detectable. After the treatment of the sera with papain and
      phosphatidylinositol-specific phospholipase C, which release membrane-associated
      AP from membrane particles, H-Mr AP was no longer detectable. These results
      indicate that H-Mr AP in the sera of patients with solid tumors may derive from
      increasing cell shedding of the tumor cells with elevated levels of membrane
      fragments in serum, which is a well known phenomenon in liver tumors. H-Mr AP was
      not more detectable in the serum after successful tumor treatment. These data
      suggest that H-Mr AP was produced by the tumors and that this parameter may be a
      serological marker for some solid tumors even in the presence of normal total AP
      serum activity.

PMID- 8152206
TI  - Autoptic findings in HIV-1 positive children.
AB  - The growing incidence of AIDS in children and newborns has been related to
      increasing incidence of AIDS in women. Case records were composed by 14 children
      with death occurring at different ages--from 1 hour to 12 years--and 1 female
      fetus, all with serological confirmation of AIDS. Brain and internal organs
      samples were collected at autopsy for morphological, immunohistochemical and "in
      situ" hybridization's technical examination. The prevailing extracerebral
      pathology observed at autopsy consisted of opportunistic infections. The cerebral
      findings were HIV-encephalopathy; cytomegalovirus encephalitis; vascular
      alterations such as necrosis and hemorrhage; calcifications and edema. Neurologic
      symptoms were reported in 3 children of intravenous drug-abuser mothers as drug
      withdrawal syndrome. HIV positivity in one or both the intravenous drug-abuser
      parents is the main risk factor of congenital AIDS. This factor means lack of
      care during the gestational stage and may determine relevant differences in the
      course of disease. The cerebral changes due to opportunistic infection must be
      differentiated from HIV-specific lesions; it has to be stressed that "diffuse"
      leukoencephalopathy is not AIDS-specific but can be found in every chronic
      encephalitis/encephalopathy especially in newborns and children. Chronologically,
      HIV encephalopathy appears as late manifestation of the disease, due to an
      infiltration of CNS of HIV-infected macrophages and not to an impairment of
      neuronal or glial cells infected by HIV in the early stages of the disease.

PMID- 8152207
TI  - [Intersexuality and malignancy. Case report of an unreported association between
      a malignant disease in a child with androgen resistance syndrome in comparison
      with the most frequently expected malignant tumors in children with
      intersexuality].
AB  - Patients with specific disorders in sexual differentiation have an increased risk
      for development of malignancies. The most frequent malignant tumors to be
      expected especially in childhood are gonadoblastoma (carcinoma-in-situ) by
      children with pure gonadal dysgenesis (Swyer-syndrome) with a calculated risk of
      approximately 30%. In this disorder the so called streak gonads have an age
      related, increased risk for development of malignancies. Furthermore, malignant
      tumors may be expected in children with mixed gonadal dysgenesis (in 10-20%),
      pure hermaphroditism (in the testes significantly higher than in the ovaries) and
      with androgen insensitivity syndrome. Risk values for the last are reported in
      the literature very differently. Rare disorders in this context are virilizing
      tumors of the adrenal cortex, the DRASH-syndrome (nephropathy, most male
      pseudohermaphroditism, Wilms-tumor) and similar disorders. Practical prophylactic
      and therapeutic procedures of the separate disorders respectively were discussed.
      We report about a child with androgen resistance syndrome and acute leukaemia.
      This would be to our knowledge the first description of such an unusual
      association of these two distinct disorders.

PMID- 8152208
TI  - [Increased thrombocyte count in newborn infants of drug-dependent mothers].
AB  - In a retrospective study we analysed clinical findings and hematological data of
      16 neonates born from mothers using methadone and other drugs during pregnancy.
      Most infants presented with symptoms of drug withdrawal and needed medication.
      Hemoglobin concentration and leucocyte counts were within normal limits, whereas
      all infants showed thrombocytosis after the first week of life with thrombocyte
      counts (median) of 566,750 (week 2), 628,500 (week 3), 629,500 (week 4), 617,000
      (week 5) and 639,150/mm3 (week 6). No thrombocytosis was found in 18 normal
      control infants which showed significantly lower platelet counts during the first
      days (p < 0.05) and by the second week of life (p < 0.001). The cause of this
      phenomenon is not known. Sudden infant death syndrome occurred in 1 infant. There
      are speculations that the high incidence of SIDS in this group of patients could
      be explained by thromboembolic complications in some of the cases.

PMID- 8152209
TI  - [Infiltrating intramuscular hemangioma].
AB  - The infiltrating intramuscular hemangioma has a high recurrence rate in case of
      incomplete resection. NMR is presently the most suitable diagnostic procedure to
      secure the diagnosis and to demonstrate the extent of infiltrative growth of this
      relatively rare soft tissue tumor. The case of an infiltrating hemangioma of the
      thigh in a 9 year old girl is presented, highlighting diagnostic and different
      treatment modalities.

PMID- 8152210
TI  - [Development of complete liver cirrhosis in hyperphagia-induced fatty liver].
AB  - The progression of alimentary fatty liver to liver cirrhosis is a very rare
      observation. During the year after surgical extirpation of a suprasellar
      craniopharyngioma in a seven years old boy developed severe obesity and again six
      years later at autopsy a complete liver cirrhosis with fatty liver was
      established. Injury of the ventromedial hypothalamic nuclei and resulting
      hyperphagia is the reason for the obesity following suprasellar tumours. The
      pathogenesis of liver cirrhosis following alimentary fatty liver is not
      completely evident up to now, such a progression is possible--as shown in this
      case--also in children and within a short period.

PMID- 8152211
TI  - Inflammatory intracranial aneurysms.

PMID- 8152212
TI  - Cerebral arteriovenous malformations.

PMID- 8152213
TI  - Vascular anomalies in the pediatric age group.

PMID- 8152214
TI  - An overview.

PMID- 8152215
TI  - Walter Edward Dandy: 1886-1946.

PMID- 8152216
TI  - Cerebral aneurysms, subarachnoid hemorrhage: an overview of incidence, location,
      presentation, diagnosis and therapy.

PMID- 8152217
TI  - Judging personality traits of adolescents from photographs.
AB  - Previous research has indicated that individuals can accurately judge certain
      personality dispositions of unacquainted peers after viewing facial photographs
      of them. The present investigation attempted to replicate and extend this
      finding. In Study 1, American high school seniors watched a videotape containing
      a series of facial photographs of twenty-two 14-year-old boys, and judged the
      social adjustment, good-worker attributes, and aggressiveness of each of these
      boys, using a series of bipolar scales. These impressions were then correlated
      with objective measures of these factors that had been taken previously. The
      subjects judged social adjustment, but not the other two factors, accurately. A
      second study evaluated the reliability of these findings. College students who
      were unacquainted with these boys rank-ordered them on the same three dimensions,
      using photographs of their upper bodies. The results of Study 2 were identical to
      those of Study 1, despite the differences in the judges' ages, the stimulus
      materials, and the methods of measurement.

PMID- 8152218
TI  - Perception of father's personality by addicts and nonaddicts.

PMID- 8152219
TI  - Gender differences in intelligence among Chinese children.

PMID- 8152220
TI  - Masculinity-femininity in East African dreams and personality.

PMID- 8152221
TI  - Dose-related doxorubicin effect in an orthotopic secondary lung cancer screen.
AB  - Lung cancer is the leading cause of cancer-related death of both sexes in the
      United States and promises to be a major problem in the world community for
      decades. We are developing an orthotopic (organ specific) secondary screening
      system to measure the uptake and efficacy of new lung cancer agents. The elements
      of the system are: (1) orthotopic growth of a model human lung cancer (NCI-H460
      large cell carcinoma) in the right caudal lobe of the nude rat; (2) 1-hr ex vivo
      pulmonary perfusion treatment of the tumor-bearing lungs; and (3) soft agar
      clonogenic assay of the enzymatically disaggregated tumor cells. This study
      characterizes dose-response aspects of the system. Perfusion of tumor-bearing
      lungs with 0, 1, 10, and 100 micrograms/ml doxorubicin resulted in a dose-related
      reduction in surviving fraction from 1.01 +/- 0.41 to 0.019 +/- 0.006 (P < 0.05)
      without significant treatment-related increases in lung weight or perfusion
      pressure. Tumor and lung drug levels were also dose-related, with lung levels
      exceeding tumor levels at all doses. The tumor drug level at the 100
      micrograms/ml dose was 62 +/- 16 ng/mg. There was a strong negative correlation
      between the measured tumor drug level and surviving fraction in the clonogenic
      assay (R2 = 0.47, P = 0.0005). This new screening system is capable of
      demonstrating dose-related uptake and tumoricidal activity of doxorubicin on an
      orthotopic, model human large cell lung carcinoma. It may be useful for the
      secondary screening of agents active against human lung cancer.

PMID- 8152222
TI  - Chemical stabilization of cartilage matrix.
AB  - Severe destruction of articular cartilage in osteoarthritis manifests clinically
      when repair processes cannot keep up with the catabolic processes. Loss of
      proteoglycans, which give the tissue its ability to undergo reversible
      deformation, precedes and probably contributes significantly to breakdown of the
      matrix in the most superficial layers of articular cartilage. In this study, we
      have examined the ability of dithiobis[succinimidyl propionate], a bifunctional
      reagent with a 1.2-nm span that cross-links proteins at lysine amino acid, and
      poly-L-lysine of high molecular weight (average MW 360,000) to reduce passive
      loss of proteoglycans and collagen from thin slices (40 and 200 microns) of
      bovine nasal and human patellar cartilage incubated for 7 days in buffer at 4
      degrees C. We present evidence that treatment of thin slices of cartilage with
      either of these agents is effective in reducing the loss of proteoglycans and
      collagen from the cartilage matrix and we define conditions (length of treatment
      and concentrations required) under which the stabilization of the cartilage
      matrix is optimized. Chemical stabilization of cartilage matrix may become an
      important modality of treatment in osteoarthritis by protecting the environment
      around chondrocytes during the repair process.

PMID- 8152223
TI  - Evidence for cytoprotection by prostaglandin E1 with normothermic hepatic
      ischemia.
AB  - Although the liver is relatively resistant to normothermic ischemia, prolonged
      periods of inflow occlusion have produced evidence of hepatocyte injury. We have
      developed an animal model of liver ischemia using the pig and maintaining
      subtotal inflow (hepatic artery and portal vein) occlusion, allowing mesenteric
      portal decompression via patent portal veins through the caudate lobe, obviating
      the need for portosystemic shunting. This produced biochemical [aspartate
      transaminase (AST), lactate dehydrogenase (LDH)] and histopathologic evidence,
      using a microscopic grading system, of hepatocyte necrosis after 2 hr of
      normothermic ischemia. By administration of prostaglandin E1 (PGE1) prior to and
      during inflow occlusion, we have produced a statistically significant reduction
      in LDH (1085.9 +/- 413.5 U/liter compared to 669.1 +/- 161.4 U/liter) and AST
      (236.5 +/- 80.4 U/liter compared to 85.1 +/- 39.7 U/liter) (P < 0.05) between
      control and PGE1 animals 24 hr after reperfusion. Moreover, using the blinded
      microscopic grading system for hepatocellular necrosis, we have found
      significantly less (2.86 +/- 0.90 compared to 1.57 +/- 1.13, P < 0.01) necrosis
      when control and PGE1 animals were compared. Our experimental model supports the
      hypothesis that PGE1 exerts a cytoprotective effect during prolonged normothermic
      hepatic ischemia but does not aid in elucidating a mechanism for this effect.

PMID- 8152224
TI  - Modulation of postsurgical cell infiltration and fibrinolytic activity by
      tolmetin in two species.
AB  - Previous studies showed that tolmetin administered as a single instillate
      intraperitoneally at the end of surgery can reduce adhesion formation. In this
      report, studies on the mechanism by which this occurs were conducted. The effects
      of tolmetin administered intraperitoneally on red (RBC) and white blood cell
      (WBC) number, macrophage and polymorphonuclear neutrophil infiltration, protease
      activity in lavage fluid, and the fibrinolytic activity of a biopsy of
      nonsurgical and traumatized peritoneal sidewall were examined. Tolmetin was shown
      to increase the number of RBC at one postoperative time point in rabbits, but not
      in rats. In addition, tolmetin administration elevated the number of WBC
      harvested from the peritoneum predominantly through an increase in macrophage
      number. Administration of tolmetin also modulated the level of protease and
      protease inhibitor activity in the lavage fluid harvested from the peritoneum.
      The most pronounced change was a decrease in the level of plasminogen activator
      inhibitor activity. In addition, acute administration of tolmetin to rats
      elevated the level of fibrinolytic activity at the site of trauma as measured by
      in vitro cultures. In summary, intraperitoneal administration of tolmetin, a
      nonsteroidal anti-inflammatory drug which reduces adhesion formation in both rats
      and rabbits, at the end of surgery modulated the number of WBCs in the peritoneal
      cavity and the protease and protease inhibitory activities present in the
      peritoneal lavage fluid and peritoneum after surgery.

PMID- 8152225
TI  - dT diaphorase: increased enzyme activity and mRNA expression in oxidant stress of
      skin.
AB  - DT diaphorase is a flavoprotein that enzymatically transfers two electrons from
      quinones as intermediate substrates and has been reported to increase its
      activity in the liver after exposure to toxicants. In this series of experiments,
      we tested the hypothesis that DT diaphorase also increases its activity after
      exposure to oxidants following gradient ischemia in skin. Using dorsal rat flaps,
      oxidant stress was induced immediately or during a 7-day period of
      preconditioning as a bipedicle flap before the distal attachment was divided. DT
      diaphorase activity (delta Abs/min/100 g) or expression of message was measured
      during the period of preconditioning to determine the relationship between skin
      survival, enzyme activity, and expression of message. There was 4.7 +/- 0.8 cm of
      skin necrosis in the distal end of acute flaps while the preconditioned flaps had
      no skin necrosis after the distal attachment was divided. In the acute flaps, the
      DT diaphorase activity was equal throughout the flap for the first 6 hr. After 24
      hr of ischemia, the DT diaphorase activity was significantly higher in the
      proximal end of the flap (1.83 +/- 0.21 delta Abs/min/100 g) than that in the
      distal end (0.005 +/- 0.01 delta Abs/min/100 g), which was significant (P <
      0.05). In the preconditioned flaps, enzyme activity did not increase but there
      was as 50-fold increase in DT diaphorase activity at the distal end 24 hr after
      they were divided (P < 0.05). Maximal enzyme induction of DT diaphorase activity
      occurred after 4 days of preconditioning and correlated with the maximal
      expression of mRNA. These studies provide the first evidence that DT diaphorase
      enzyme activity is inducible after oxidant stress. The data also suggests that DT
      activity remains elevated for at least 6 hr of ischemia and may be a potential
      source of anti-oxidant activity in ischemic skin.

PMID- 8152226
TI  - Changes in protein distribution in the rat during prolonged "systemic injury".
AB  - A model of prolonged systemic injury was generated in the rat by three sequential
      injections of turpentine, delivered at 2-day intervals. The model was then used
      to identify the subsequent changes in the distribution of tissue protein and the
      effects of the changes in skin protein on the tensile strength of healing skin
      wounds. The model produced a sustained acute phase response during the 6 days of
      the study, including a significant (26%) reduction in the plasma glutamine
      concentration (P < 0.01), which was not achieved with a single injection of
      turpentine. When compared with pair-fed controls, the animals injected with
      turpentine had 18% more nitrogen in the liver (P < 0.05), 25% less in the
      gastrocnemius muscle (P < 0.01), and a similar amount in the upper small
      intestine. There was also a 30% loss of nitrogen from dorsal skin (P < 0.001) and
      a 15% loss from ventral skin (P < 0.01), with a parallel loss of collagen
      (measured as hydroxyproline). Ten days after the first injection of turpentine,
      the dorsal skin was still 18% thinner than that of the pair-fed controls (P <
      0.01): this was associated with an 18% reduction in the bursting strength of
      linear skin wounds (P < 0.05). Such changes were not observed in pair-fed
      controls. These studies demonstrate that systemic injury (independent of dietary
      intake) causes a preferential loss of protein from peripheral tissues (skin,
      muscle) and preservation of protein in splanchnic tissue (liver, intestine). They
      also suggest that the loss of skin protein including collagen is quantitatively
      important, with functional consequences in reducing the bursting strength of
      surgical skin wounds.

PMID- 8152227
TI  - On-line search strategies of third year medical students: perception vs fact.
AB  - The curriculum at the University of New Mexico School of Medicine has evolved
      with a high priority on problem-based and life-long learning. As the information
      pool enlarges, a greater emphasis must be placed on the ability of physicians to
      access the biomedical literature following residency training. To foster
      information retrieval skills, our medical school has included on the ability of
      physicians to access the biomedical literature following residency training. To
      foster information retrieval skills, our medical school has included on-line
      searching instruction since 1987. On-line classes are taught by experienced
      medical librarians during the second month of the first year curriculum. After
      receiving training, students are assigned a code via Grateful Med software. The
      purpose of the study was to measure the long-term effectiveness of this training
      approach and to determine the students' ability to formulate a search strategy
      and run a search to answer clinical questions at the third year level. During the
      1990-1991 school year, all third year students were asked to use Grateful Med to
      answer two questions related to surgical patient care and to complete a
      questionnaire showing how they use Grateful Med and how they view their training.
      The students' searches were compared to "gold standard" searches run by an
      experienced medical librarian. Nineteen percent of all searches resulted in zero
      retrieval, and the remainder missed 74-100% of the gold standard available
      citations. Additional instruction shortly after on-line training could identify
      problem areas (poor search behavior) and information retrieval skills should be
      integrated and encouraged in all levels of the curriculum.

PMID- 8152228
TI  - Small intestinal microcirculatory effects of octreotide.
AB  - Somatostatin and its analogue, octreotide acetate, are thought to decrease
      mesenteric blood flow; however, it is unknown whether the decrease occurs at the
      central, regional, or microvascular level. We hypothesized that the circulatory
      effects of octreotide are regulated at the microvascular level. Changes in
      superior mesentery artery (SMA) flow in response to octreotide were measured with
      a perivascular ultrasonic flow probe. In separate experiments, the jejunal
      microcirculatory effects of octreotide were studied using in vivo
      videomicroscopy. After accrual of baseline hemodynamic and microcirculatory data,
      animals were randomized to control or treatment (10 micrograms/kg octreotide) iv
      groups. Measurements were made every 15 min during the infusion and for 90 min
      after the completion of the infusion. Results are expressed as means +/- SEM.
      Intravenous infusion of octreotide caused no significant change in arterial
      pressure, cardiac index, or systemic vascular resistance index in either group in
      either set of experiments. A statistically significant decrease in heart rate
      (9%) occurred in the control group of animals undergoing SMA flow measurement.
      SMA flow did not change significantly with infusion of octreotide. In contrast,
      jejunal first-order arteriole flow increased to 117.9 +/- 9.7% of baseline (P <
      0.05) in the absence of significant changes in microvessel diameters. This was
      due to an increase in centerline red cell velocity (116 +/- 5% of baseline, P <
      0.05). We conclude that octreotide increases jejunal first order arteriole flow
      by mechanisms that are regulated at the microcirculatory level.

PMID- 8152229
TI  - Glutamine preserves gut glutathione levels during intestinal
      ischemia/reperfusion.
AB  - Intestinal ischemia/reperfusion (I/R) causes formation of reactive oxygen
      intermediates (ROI) which lead to mucosal cell injury. Glutathione (GSH), an ROI
      scavenger, protects tissues from ROI-mediated cell injury. Since GSH biosynthesis
      is partially dependent on glutamine (Gln) levels, we tested the hypothesis that
      intravenous Gln infusion will assist in maintaining mucosal cell GSH levels and
      decrease membrane lipid peroxidation during intestinal I/R. The external jugular
      vein of male Sprague-Dawley rats was cannulated and infused with normal saline
      (NS) at 2 cc/hr. After 3 days, matched pairs of rats received either NS alone or
      NS+ 3% Gln for an additional 24 hr. Next, mucosal GSH levels were measured after
      a sham I/R in 6 rats and after either 30 or 60 min of ischemia/60 min of
      reperfusion in a group of 8 and 12 rats, respectively. Finally, conjugated diene
      (CD), a byproduct of membrane lipid peroxidation, was measured following 60 min
      of ischemia/60 min of reperfusion in a separate group of 12 rats. Control rats
      had the highest GSH levels and there was no difference between NS vs NS + 3% Gln
      rats (2.50 +/- 0.48 vs 2.50 +/- 0.43, P = NS). With 30 and 60 min of ischemia/60
      min of reperfusion, GSH levels were significantly lower in NS-infused rats
      compared to those in NS + 3% Gln-infused rats (30 min: 1.54 +/- 0.14 vs 1.80 +/-
      0.16, P < 0.05; 60 min: 1.27 +/- 0.15 vs 1.52 +/- 0.20, P < 0.04). In addition,
      CD levels were lower in NS + 3% Gln-infused rats compared to those in NS alone
      infused rats (5.58 +/- 0.87 vs 7.94 +/- 0.55, P < 0.04). In conclusion, Gln
      supplementation partially maintains gut GSH levels during bowel I/R, which in
      turn lessens I/R-induced cell membrane lipid peroxidation.

PMID- 8152230
TI  - 5'-Nucleotidase inhibition enhances postischemic myocardial performance.
AB  - Adenosine methylene diphosphate (AMPCP), a 5'-nucleotidase inhibitor, was
      evaluated as an adjunct to cold crystalloid cardioplegic myocardial protection.
      Cardiopulmonary bypass (CPB) was instituted at 28 degrees C in two groups of
      mongrel dogs (each, n = 6). Myocardial ischemia was induced for 150 min by aortic
      cross clamping. Crystalloid cardioplegia (4 degrees C) was infused into the
      aortic root at 15 ml/kg/20 min in the control group (CP). The experimental group
      (CP + AMPCP) received identical doses of cardioplegia supplemented with 250
      microM AMPCP. While on CPB, the mean arterial pressure was 70 mm Hg and the
      myocardial temperature ranged from 16 to 22 degrees C. Hemodynamic parameters
      were recorded prior to institution of CPB and at 15 and 45 min following the
      termination of CPB. Starling curves were constructed for cardiac index (CI), mean
      arterial pressure (MAP), mean left ventricular pressure (LVP), +dP/dt and -dP/dt
      at each time point for left atrial pressures between 5 and 12.5 mm Hg. The area
      under each curve was calculated and expressed as a percentage of prebypass
      values. Statistical analysis was performed with Student's two-tailed t test. The
      data demonstrate that although recovery of CI, MAP, heart rate, and LVP was
      similar in both groups, statistically significant improvement in recovery of
      myocardial compliance (-dP/dt) and systolic function (+dP/dt) was seen with
      AMPCP. The addition of the 5'-nucleotidase inhibitor, AMPCP, to cold crystalloid
      cardioplegia enhances postischemic myocardial performance in vivo and may be
      useful during prolonged periods of global myocardial ischemia.

PMID- 8152231
TI  - Decreased lactate in endotoxin-resistant mice undergoing hemorrhage is
      independent of tumor necrosis factor availability.
AB  - Although C3H/HeJ mice, characterized by a genetic deficiency in macrophage
      cytokine release in response to endotoxin, have been studied extensively to gain
      insight into the possible role of various cytokines in sepsis, few past studies
      have examined the physiologic response to hemorrhagic shock in this "endotoxin
      resistant" strain. We utilized a fixed-volume model of hemorrhagic shock and two
      different levels of hemorrhage severity (50 and 67% blood volume) to compare
      C3H/HeJ mice to normal C3H/HeN mice. An additional group of endotoxin-sensitive
      C3H/HeN mice were treated with 2.5 mg/kg of anti-tumor necrosis factor (TNF)
      antibody to define the possible role of TNF in shock physiology. Hematocrit,
      circulating neutrophils, and plasma glucose and lactate concentrations were
      measured following hemorrhage. TNF increased significantly following hemorrhage
      in normal mice but did not increase in C3H/HeJ mice or in C3H/HeN mice treated
      with anti-TNF antibody. No difference between groups was identified in
      hematocrit, circulating neutrophils, or glucose. Whereas plasma lactate increased
      significantly by 30 min in all groups, lactate returned to baseline levels in
      C3H/HeJ mice at 60 min, but remained persistently elevated in C3H/HeN mice and in
      C3H/HeN mice treated with anti-TNF antibody. The data demonstrate attenuated
      lactate accumulation in C3H/HeJ mice following hemorrhage. Inhibition of
      circulating TNF activity with anti-TNF antibody failed to reproduce this late
      decrease in plasma lactate in normal mice. The data suggest that macrophage
      products other than TNF known to be deficient in C3H/HeJ mice contribute to
      anaerobic metabolism in hemorrhagic shock.

PMID- 8152232
TI  - Successful engraftment of autologous and allogeneic islets into the porcine
      thymus.
AB  - Work in rodents has shown that injection of pancreatic islets of Langerhans into
      the thymus can induce donor-specific unresponsiveness to islets subsequently
      transplanted to extrathymic sites. The overall objective of our investigation is
      to test this in a large animal (pig) model. In the current study we examined
      whether autologous and allogeneic adult or fetal islets survive in the porcine
      thymus. Collagenase-digested adult and fetal porcine islets were injected into
      the thymic lobes of 5- to 13-month-old, normal pigs. Pigs receiving allografts
      were given either a standard triple regimen of oral cyclosporine, azathioprine,
      and prednisone or intravenous anti-lymphocyte globulin (ALG) for
      immunosuppression. Two pigs of each group that received an allograft or autograft
      were given no immunosuppression. Biopsies of the grafts were taken at 4, 6, or 12
      weeks for examination. Islet survival was assessed by histology with hematoxylin
      and eosin and insulin staining and by measurement of tissue insulin content using
      acid alcohol extraction and radioimmunoassay. The insulin content of control
      thymus was found to be 0.71 +/- 0.29 microU/mg (n = 5). The insulin content of
      the islet-grafted thymic tissues ranged from 1.57 to 10.65 microU/mg. Since the
      amounts of injected islets were not equal and not distributed evenly, and only a
      part of the graft site was used for determination of tissue insulin, thymic
      insulin contents higher than 1.4 microU/mg (twice that of the control value) were
      considered to demonstrate the presence of viable islets. With this criterion, we
      concluded that islets were found to be viable in seven of nine pigs and two pigs
      which were treated with ALG were shown to be marginally positive. On histological
      examination, islets were found in the thymus as well as under the thymic capsule,
      except for the above two pigs. These results demonstrate that the pig thymus
      supports fetal and adult islet transplants.

PMID- 8152233
TI  - Mechanical comparison of 10 suture materials before and after in vivo incubation.
AB  - The material properties of ten 2-O suture materials were evaluated
      tensiometrically at time = 0 and again after 6 weeks incubation in rats. All
      suture material was incubated and tested without knots. Specialized machinery was
      used with a custom securing apparatus to pull suture material apart at constant
      speed. Stress-strain curves were derived, and from these strength, toughness,
      strain at rupture, and elastic modulus were determined. Sutures tested included
      Vicryl [poly(glycolide-lactide)], Dexon (polyglycolic acid), Ethibond
      (polyester), silk, plain gut, chromic gut, Maxon (polyglyconate), PDS
      (polydioxanone), nylon, and Prolene (polypropylene). Elastic modulus was greatest
      for braided, least for monofilament, and intermediate for gut sutures, regardless
      of chemical composition (ANOVA, P = 0.0001). Strength, strain, and toughness
      decreased in all of the sutures over time in vivo with the exception of braided
      polyester (Ethibond), which remained stable. Silk demonstrated the least strength
      and toughness while PDS and Maxon were the strongest and toughest at time = 0.
      Vicryl, Dexon, and gut sutures were absorbed to the point that they could not be
      tested after 6 weeks in vivo. Performance tables are provided for all sutures.

PMID- 8152234
TI  - Cytoprotection of human dermal fibroblasts against silver sulfadiazine using
      recombinant growth factors.
AB  - Topical antimicrobial agents, silver sulfadiazine (SSD) and mafenide acetate
      (MA), have been associated with delayed wound healing. Previous in vitro studies
      with human dermal fibroblasts (HDF) have shown progressive cellular cytotoxicity
      with increasing concentrations of SSD and MA. However, preexposure of HDF to
      epidermal growth factor, basic fibroblast growth factor, or platelet-derived
      growth factor has resulted in cytoprotection of HDF against 0.01 and 0.03%
      concentrations of SSD as determined by phase-contrast microscopy (PCM),
      hemocytometer cell counts, and total cellular protein content. PCM, however,
      showed slower destruction of HDF at the 0.05% concentration of SSD. These data
      suggest that cells activated by growth factors either take up less SSD or are
      more resistant to the direct cytotoxic effects of this drug.

PMID- 8152235
TI  - HIV infection/AIDS: a clinician's perspective.
AB  - HIV infection and AIDS presents complex issues for all mankind. With every day
      that passes, 5000 more people worldwide become infected with the virus. Young
      people and adults alike need frank and clear information regarding how to protect
      themselves and others. Even though the vast majority of HIV infections are spread
      through sexual intercourse it is the health care provider and, in particular, the
      dental professional who is impacted by efforts to prevent the transmission of
      HIV. It is the obligation of every dentist to understand HIV infection and
      related HIV diseases. The dental professional should be familiar with the
      epidemiology of HIV, medical as well as oral manifestations of the disease, and
      legal and ethical considerations of this pandemic. This manuscript is intended
      only to be an overview of the worldwide crisis of the HIV pandemic and its impact
      on all of us as individuals as well as the dental profession.

PMID- 8152237
TI  - "The good ole days".

PMID- 8152236
TI  - Risk communication in dental practice: responding assertively to AIDS, fear and
      infection control.
AB  - There is great value in applying the science of risk communication in
      contemporary dental practice. Dental professionals can respond most assertively
      to anxious patients by developing active listening skills while engaging
      patients' negative beliefs and attitudes regarding dental care in the age of
      AIDS. This paper addresses the need to reestablish dental professional confidence
      and credibility along with patient trust through a grass-roots effort of applying
      risk communication strategies for improved dental public relations.
      Recommendations are provided to enable dental professionals to achieve optimal
      success in responding to the psychological, emotional and economic challenges of
      AIDS, irrational fear, and media-driven concerns about dental office infection
      control.

PMID- 8152238
TI  - Determination of 18F-fluoro-2-deoxy-D-glucose rate constants in the anesthetized
      baboon brain with dynamic positron tomography.
AB  - We have determined the rate constants (ki*) of 18F-fluorodeoxyglucose (FDG) in
      the unlesioned baboon brain, for use in positron emission tomography (PET)
      measurements of glucose utilization. In contrast to earlier reports, we used a
      radiosynthesis which guarantees production of FDG essentially uncontaminated by
      fluorodeoxymannose, and an improved determination of ki* by (1) direct
      measurement of the time-shift between bolus arrival in femoral arterial plasma
      and brain, (2) rapid initial PET frames, and (3) extended data acquisition (up to
      180 min). Young adult baboons were studied under anesthesia with either
      phencyclidine or etomidate. The FDG time-activity curves obtained from temporal
      grey matter showed a consistent decline after about 80 min, indicating true
      product loss. Three-compartment modelling was performed for increasing fitting
      intervals (20-120 min) with both a 5-parameter (K1*-k4*, and vascular volume
      (Vo)) and a 4-parameter (K1*-k3*,Vo) model. With the latter, both the calculated
      FDG net clearance ((K* = K1*.k3*/(k2* + k3*)) and the fitted kinetic constants
      were dependent on fitting interval, i.e., they showed sustained unstability. With
      the former, the constant k4*, which presumably represents dephosphorylation, was
      overestimated and unstable for short fitting times (presumably due to
      heterogeneous brain compartments in the sample tissue), but stabilized at
      approximately 0.01 min-1 for fitting times > or = 80 min; K1*-k3* and K* were
      also stable after this time. These findings were identical for both anesthetic
      regimen. Thus, in the anesthetized baboon, the FDG ki* values can be reliably
      determined based on an adequate PET acquisition paradigm and with a model that
      incorporates k4* and > or = 80 min time-activity data.

PMID- 8152239
TI  - Simultaneous "real-time" electrochemical and electrophysiological recording in
      brain slices with a single carbon-fibre microelectrode.
AB  - Many previous studies have demonstrated the value of carbon-fibre microelectrodes
      (CFMs) for single-unit activity recording and for fast cyclic voltammetry. In
      this report we show that these two independent methodologies can be combined at a
      single CFM and used to study simultaneous electrochemical and
      electrophysiological events in brain slices. In superfused slices of rat locus
      coeruleus, dorsal raphe and substantia nigra, we were able to record stable
      electrophysiological signals and stimulated monoamine efflux for periods of at
      least 2 h, thereby allowing quantitative pharmacological interventions. The
      simultaneous recording of amine efflux and unit activity at the same locus
      facilitates comparison of drug effects at pre- and post-synaptic sites.
      Furthermore, the system described here uses commercially available
      instrumentation. The circuitry is described and examples of its application are
      shown.

PMID- 8152240
TI  - A simplified method for selecting a carbon-fiber electrode in pulse voltammetry.
AB  - A method for selecting a usable carbon-fiber electrode using the equivalent
      resistance and capacitance is presented. This method uses an instrument with a PC
      based look-up table for measuring the electrical characteristics of a carbon
      fiber electrode in pulse voltammetry. Using this instrument, the equivalent
      resistance and capacitance of the carbon-fiber electrode in saturated sodium
      chloride solution can be obtained. This instrument includes a decade resistance
      box, a peak current detection and hold circuit, a half peak comparator and a
      decay duration counter. A look-up table is established by using RC circuits to
      emulate the electrochemical reaction of the carbon-fiber electrode in pulse
      voltammetry. The equivalent resistance is obtained from the decade resistance box
      according to Kirchhoff's law. Then the equivalent capacitance is determined from
      the decay duration counter reading and equivalent resistance with the look-up
      table via a PC interpolation program. After obtaining the equivalent resistance
      and capacitance of an electrode, the values are compared with the usable
      thresholds. This method provides an effective quality evaluation index of carbon
      fiber electrode for the user in order to reduce electrode-induced experimental
      failure. The method is also available for other kinds of carbon-fiber electrodes
      as long as their look-up table and desired thresholds are established.

PMID- 8152241
TI  - Neurologic evaluation in a canine model of single and double subarachnoid
      hemorrhage.
AB  - The pathophysiology of cerebral vasospasm is complex and multifactorial. The
      present study sought to identify the degree of correlation between cerebral
      vasospasm as observed angiographically and clinical evaluation of an animal's
      neurologic status in the canine model following a single and double experimental
      subarachnoid hemorrhage (SAH) protocol. Nineteen mongrel dogs underwent single or
      double experimental SAH by percutaneous needle puncture of the cisterna magna and
      placement of a subarachnoid blood clot in the basal cistern on day 1 and day 4,
      respectively. At 72 h after each experimental SAH, vertebral angiography was
      performed and compared to control angiography. Basilar artery diameter measured
      at multiple positions was expressed as percentage of control diameter. Clinical
      evaluation of the animals was performed every day throughout the experiments. To
      assess the degree of neurologic impairment we developed a coma scale that
      efficiently estimated motor ability, eye response and eating habits of the
      animals. Vasoconstriction after experimental SAH reduced mean basilar artery
      diameter to 79.1% (+/- 5.4) of control diameter following single SAH and to 69.0%
      (+/- 2.1) of control diameter following double SAH. No changes were observed in
      the neurologic behavior of the animals throughout the experiment. Since a
      principal characteristic of human cerebral vasospasm is the close correlation
      between arterial constriction and neurological deficit, we believe that the
      canine model of SAH, although good in creating cerebral arterial
      vasoconstriction, does not fully represent the best model of human cerebral
      vasospasm.

PMID- 8152242
TI  - An optimized method for determining cytochrome oxidase activity in brain tissue
      homogenates.
AB  - We have developed a method to accurately and reproducibly determine the total
      activity of cytochrome oxidase (CO) in rat brain tissue homogenates. Previously,
      accurate measurements have been difficult to obtain because detergents, which are
      needed to disrupt membranes and unmask CO, also inhibit the enzyme by
      solubilizing certain phospholipids required for rapid turnover. We compared
      various methods of sample preparation, and found that maximal CO activity in
      homogenates could be obtained using specific concentrations of detergents. The
      range of optimal detergent concentrations was relatively narrow, as CO activity
      fell sharply with small deviations from the optimum. Of 5 detergents tested,
      deoxycholate stimulated CO maximally over the widest range of concentrations. In
      deoxycholate-treated homogenate samples, the calculated CO turnover number was
      about 480 s-1, indicating that overall enzyme activity was maximal or near
      maximal, and therefore that the total content of CO was probably detected. This
      method was reproducible with large or small samples (e.g., < 1 mg tissue), and
      should be applicable to studies of neural tissue in general.

PMID- 8152243
TI  - Lucifer Yellow staining in fixed brain slices: optimal methods and compatibility
      with somatotopic markers in neonatal brain.
AB  - Developing dendritic trees often acquire their mature form by selective pruning
      and reorientation relative to anatomical boundaries, such as cortical 'barrel'
      walls. Whether similar constraints are imposed on the developing dendrites of
      subcortical somatosensory neurons is not clear, although it is known that the
      cells in trigeminal nucleus principalis (PrV) of adult rats have polarized trees.
      In attempting to resolve this issue we adopted and subsequently optimized a
      strategy of intracellular injection of Lucifer Yellow into PrV neurons and
      cerebellar granule cells in slices of fixed brain. Postinjectionally,
      immunohistochemical staining produced a stabilized image of the Lucifer Yellow
      injected cells and created the opportunity to apply also an antiserum to J1
      tenascin in order to detect whisker-related compartmental boundaries in the
      neonatal PrV. In 6-day-old rats, most PrV dendrites are polarized and they do not
      cross tenascin-stained, whisker-related, patch borders. Notable exceptions are
      dendrites from the minority of PrV cells that have large somata and are
      responsive to multiple whiskers.

PMID- 8152244
TI  - Localized gene transfer into organotypic hippocampal slice cultures and acute
      hippocampal slices.
AB  - Viral vectors derived from herpes simplex virus, type-1 (HSV), can transfer and
      express genes into fully differentiated, post-mitotic neurons. These vectors also
      transduce cells effectively in organotypic hippocampal slice cultures. Nanoliter
      quantities of a virus stock of HSVlac, an HSV vector that directs expression of
      E. coli beta-galactosidase (beta-gal), were microapplied into stratum pyramidale
      or stratum granulosum of slice cultures. Twenty-four hours later, a cluster of
      transduced cells expressing beta-gal was observed at the microapplication site.
      Gene transfer by microapplication was both effective and rapid. The titer of the
      HSVlac stocks was determined on NIH3T3 cells. Eighty-three percent of the beta
      gal forming units successfully transduced beta-gal after microapplication to
      slice cultures. beta-Gal expression was detected as rapidly as 4 h after
      transduction into cultures of fibroblasts or hippocampal slices. The rapid
      expression of beta-gal by HSVlac allowed efficient transduction of acute
      hippocampal slices. Many genes have been transduced and expressed using HSV
      vectors; therefore, this microapplication method can be applied to many
      neurobiological questions.

PMID- 8152245
TI  - Extracti-Gel D chromatography is a simple, efficient method for removing
      digitonin during receptor purification: application to the kappa 1 opioid
      receptor.
AB  - Digitonin is widely used for extracting active neurotransmitter receptors from
      membranes. However, its low critical micellar concentration has made its removal
      from samples problematic. Here we report that digitonin can be efficiently
      removed (> 90%) from solution using Extracti-Gel D, a detergent-absorbing matrix.
      Active kappa 1 opioid receptors solubilized from brain survive Extracti-Gel D
      chromatography with a recovery of 50-55% and 25% dilution by added volume. The
      loss of receptor and the dilution, however, are compensated for to a large extent
      by the disinhibition of binding that results from the removal of digitonin.
      Extracti-Gel D chromatography had little or no effect on the apparent equilibrium
      dissociation constant for [3H]U-69,593 binding to the kappa 1 receptor. We
      conclude that Extracti-Gel D column chromatography is a simple, highly efficient
      and practical method for markedly reducing the concentration of digitonin in
      biological samples. Application of the procedure should allow characterization of
      digitonin-solubilized receptors with minimal complications from bound digitonin
      and extend the usefulness of digitonin to studies going beyond the initial stages
      of receptor purification.

PMID- 8152246
TI  - A versatile technique for patterning biomolecules onto glass coverslips.
AB  - A fast, inexpensive, and versatile technique for patterning the surface of glass
      coverslips with molecules of biological interest is described. The technique
      combines photolithographic, silane-coupling, and protein adsorption procedures to
      pattern coverslips with amines, alkanes, and proteins with micrometer spatial
      resolution. The attachment of amines and alkanes was verified using contact angle
      and X-ray photoelectron spectroscopic (XPS) measurements. XPS results showed that
      amines and alkanes were attached in 1-4 nm thickness covering approximately 20%
      and 45%, respectively, of the surface. Patterns of amines were visualized using
      fluorescent staining, and patterns of proteins were detected immunochemically.
      Patterned coverslips were used to investigate adhesion and neurite outgrowth of
      mouse neuroblastoma (N1E-115) cells. Cells were examined on the following
      patterns: alkane-glass, protein-glass, amine-alkane, and amine-protein. Cell
      attachment and neurite outgrowth on patterned coverslips displayed the following
      preferences: laminin, fibronectin, or collagen IV > amine or glass > alkane or
      bovine serum albumin. This patterning method should be useful for studies of cell
      surface interactions, cell migration, nerve regeneration, and the formation of
      neural networks in vitro.

PMID- 8152247
TI  - Phase I-II trial of high dose Ara-C, carboplatinum, etoposide and steroids in
      patients with refractory or relapsed lymphomas.
AB  - Thirty-three patients, including 20 with non-Hodgkin's lymphomas (NHL) and 13
      patients with Hodgkin's disease, were treated with a combination of high dose Ara
      C 3 gm/m2 over 3 h, carboplatinum 300 mg/m2 over 15 min, etoposide 300-750 mg/m2
      continuous infusion over 24 h and solumedrol 1250 mg. Probantheline was given
      prophylactically. The etoposide dose was escalated from 300 mg/m2 to 600 mg/m2 to
      750 mg/m2. The median age was 44 years (range 28-63). Median Karnofsky
      performance status was 80 (range 60-100). Patients treated included: primary
      refractory six, first relapse 14, > first relapse seven, and resistant relapse
      six. Responses were seen in 11 patients (33%; 95% CI 17-49). Of note, no
      responses were seen in ten patients receiving < 750 mg/m2 etoposide vs. 11/23
      patients receiving 750 mg/m2 etoposide (p = 0.013). Responses were seen in
      patients who were refractory to previous chemotherapy and occurred in all sites.
      Toxicity was tolerable with most patients not requiring hospitalization following
      chemotherapy. Two patients died on study: one of Guillain-Barre syndrome and the
      other of a sudden death. Severe mucositis was not observed. High dose etoposide
      based salvage chemotherapy offers a greater probability of response than lower
      dose etoposide. This regimen is well tolerated and can be administered with
      relatively brief hospitalization.

PMID- 8152248
TI  - Post-remission cytopenias following intense induction chemotherapy for acute
      myeloid leukemia.
AB  - Forty-five patients with untreated, de novo acute myeloid leukemia (AML) were
      treated with high-dose cytosine arabinoside (Ara-C) plus mitoxantrone or
      daunorubicin. Forty-two patients entered complete remission with recovery of
      normal blood counts. Seven of these patients were excluded from further analysis
      (two, early consolidation chemotherapy; four, early relapse; one, hypersplenism).
      Of the remaining 35 patients, 20 (57%) developed thrombocytopenia and anemia
      (with or without neutropenia) a median of 3 weeks after entering complete
      remission. Post-remission cytopenias were more common in patients receiving
      mitoxantrone (81%) compared to those receiving daunorubicin (37%; p < 0.003). The
      cytopenias lasted a median of 54 days. Four of five patients in whom the
      cytopenias did not recover received mitoxantrone. Leukemia relapse or
      myelodysplasia did not explain these cytopenias. Post-remission cytopenias
      resulted in a greater than 90-day delay or prevention of planned autologous bone
      marrow transplantation in 13 of 17 otherwise eligible patients. We conclude that
      post-remission cytopenias are common following blood count recovery in AML
      patients entering complete remission with high-dose Ara-C and mitoxantrone or
      daunorubicin. Post-remission cytopenias do not necessarily imply leukemia
      relapse.

PMID- 8152249
TI  - Molecular analysis of MLL-1/AF4 recombination in infant acute lymphoblastic
      leukemia.
AB  - We examined ten cases of acute lymphoblastic leukemia (ALL) in infants (less than
      1 year of age) by RT-nested PCR for a MLL-1/AF4 rearrangement. Five patients
      revealed a positive result. The specific PCR product differed in size from
      approximately 380-670 bp indicating various splicing variants in the MLL-1/AF4
      rearrangement. Three patients had a fusion between exon 6 of the MLL-1 gene and
      codon 362 of the known AF4 cDNA sequence. Moreover, in two patients more than one
      specific PCR product was detected, possibly due to alternative splicing. In the
      first case, sequencing of these products revealed a hybrid mRNA consisting of MLI
      1 exon 7 or exon 8, respectively, fused to the AF4 gene at codon 348. In the
      second case with alternative splicing, again, exon 7 or 8 of the MLL-1 gene were
      fused to the AF4 gene as in case 1. The AF4 sequence involved in this patient,
      however, started at codon 362. The AF4 break was, therefore, identical to the
      three MLL-1/AF4 positive patients as described above. Moreover, we investigated
      all ten patients for the reciprocal mRNA transcript AF4/MLL-1 by a similar PCR
      approach. In none of these patients, including the five MLL-1/AF4 positive cases
      was a specific PCR product obtained. However, in the MV411 cell line bearing a
      t(4;11), which served as a positive control in our MLL-1/AF4-PCR assay, the
      reciprocal AF4/MLL-1 mRNA was detected. Our results indicate that a MLL-1/AF4
      rearrangement occurs in about 50% of infants with ALL. In contrast, the
      reciprocal hybrid mRNA can only rarely be detected, if at all.

PMID- 8152250
TI  - Molecular variants of the 1;19 chromosomal translocation in pediatric acute
      lymphoblastic leukemia (ALL).
AB  - The t(1;19)(q23;p13), a non-random chromosome rearrangement associated with
      childhood pre-B acute lymphoblastic leukemia (ALL), results at molecular level in
      the hybrid E2A-PBX1 gene. This gene is expressed in a typical set of fusion
      transcripts and oncogenic chimeric proteins. However, the occurrence of t(1;19)
      molecular variants has been recently suggested. In an attempt to identify these
      variants, we analyzed 25 pediatric cases of pre-B cIg+ cell ALL. We used Southern
      blot analysis to detect E2A gene rearrangements and RT-PCR to detect chimeric E2A
      pbx1 transcripts. In addition to seven cases with the molecular pattern usually
      associated with the t(1;19), we identified three molecular variants. In one case,
      a variant E2A-pbx1 transcript showed 27 additional base pairs inserted in frame
      at the junction site. In two cases, Southern blot evidenced the expected E2A gene
      rearrangements. However, extensive RT-PCR analysis failed to detect any E2A-pbx1
      transcript. These findings led us to hypothesize that a gene other than PBX1
      might be involved in these 1;19 variant translocations.

PMID- 8152251
TI  - The t(14;18) in a patient with de novo acute lymphoblastic leukemia is associated
      with t(8;9).
AB  - Cytogenetic analysis of a bone marrow aspirate from a patient with acute
      lymphoblastic leukemia (ALL) revealed the presence of a complex karyotype
      containing the translocation, t(14;18)(q32;q21). Further investigations using
      fluorescence in situ hybridization (FISH) allowed the characterization of an
      additional translocation, t(8;9)(q24;p1?). The association of t(14;18)(q32;q21)
      and t(8;9)(q24;p13) has recently been described in two patients with de novo ALL
      (Nacheva et al. Blood 1993;82:231-240) and this report supports these findings.

PMID- 8152252
TI  - A gene on chromosome Xq28 associated with T-cell prolymphocytic leukemia in two
      patients with ataxia telangiectasia.
AB  - A t(X;14)(q28;q11) translocation was present for many years in T cells in two
      patients with ataxia telangiectasia (A-T), who subsequently developed T
      prolymphocytic leukemia. We describe here the relationship between the
      translocation breakpoints in these patients with respect to two recently
      described genes, c6.1A and c6.1B, on Xq28 which are transcribed in opposite
      directions from the same CpG island. In our first patient, the Xq28 breakpoint
      disrupts the c6.1A gene which is consequently transcribed as a fusion mRNA with
      the TCR C alpha chain gene. In the second case, the Xq28 breakpoint lies within
      the adjacent gene c6.1B, and c6.1A is not transcribed. We show that the c6.1B
      gene is transcribed in both of our patients. c6.1B may be important in the
      initial clonal proliferation of T lymphocytes which commonly precedes
      transformation to T-PLL in ataxia telangiectasia patients. The same gene may also
      be involved in the development of T-PLL in the non-A-T population.

PMID- 8152253
TI  - Expression of the X-linked agammaglobulinemia gene, btk in B-cell acute
      lymphoblastic leukemia.
AB  - The gene which causes X-linked agammaglobulinemia, btk, has recently been
      identified as a cytoplasmic tyrosine kinase expressed almost exclusively in B
      cells, and at all stages of B-cell differentiation. To assess the possibility of
      involvement of this gene in childhood B-cell malignancies, cells from 23
      pediatric patients with B-cell acute lymphoblastic leukemia were examined for
      expression and alteration of the Btk protein and also for mutations in the btk
      gene. Btk proteins, similar in both molecular weight and quantity to those seen
      in unaffected individuals, were detected in whole cell lysates from the blasts of
      12/12 patients indicating that no abnormal protein was present. cDNAs from the
      leukemic blasts of all 23 patients were screened with specific primers covering
      the coding region of the btk cDNA for mutations using single strand conformation
      polymorphism (SSCP) analysis. No mutations were found but a nucleotide
      polymorphism was identified in 4/23 patients at the 3' end of btk. Although the
      sample size in this study was relatively small, these data suggest that btk does
      not appear to play a critical role in childhood B-cell leukemias.

PMID- 8152254
TI  - Hunting 11q23 deletions with fluorescence in situ hybridization (FISH).
AB  - Seven patients with acute leukemia and translocation involving band 11q23 have
      been studied by fluorescence in situ hybridization (FISH) using YAC probes
      spanning the HRX gene. While hybridization signal was split by translocation
      between the rearranged 11 and the partner chromosomes in five patients, only one
      signal on the derivative 11 was observed in two patients, one with t(9;11)(p21
      22;q23) and the other with t(6;11)(q27;q23). Having shown that HRX was rearranged
      in these two cases, the distal part of 11q23 was investigated using other YACs
      containing markers for this region. This showed that a 600-700 kb deletion,
      distal to the HRX breakpoint cluster region, had occurred in the two cases. This
      study supports the notion that the 5' end of HRX is the important part in the
      chimeric genes resulting from 11q23 translocations and suggests that deletions of
      the 3' part are not uncommon.

PMID- 8152255
TI  - Detection of minimal residual disease using fluorescence DNA in situ
      hybridization: a follow-up study in leukemia and lymphoma patients.
AB  - We used fluorescence DNA in situ hybridization (FISH) to detect chromosomal
      abnormalities as an indicator of minimal residual disease in follow-up samples
      from the bone marrow (BM), or peripheral blood, of 25 patients with leukemia,
      lymphoma and myelodysplastic syndromes. Trisomies were detected by interphase
      FISH with repeat-sequence probes (RSP) or by using metaphase FISH with whole
      chromosome paint probes (WCP). Specific translocations were detected using WCP
      probes. Translocations were observed using metaphase FISH in two patients in
      uncertain or complete remission (CR), who both later suffered relapse. Five
      patients with no abnormal cells remained in CR. Four patients with trisomies
      detected during CR suffered relapse; metaphase FISH detected the trisomy in 0.17
      16% of metaphase cells. Five patients for whom the trisomy occurred in 0.034% of
      cells remained in CR. Trisomic nuclei were observed in 0.27-2.3% of interphase
      cells, by means of RSPs, in four patients who later suffered relapse. Five
      patients with trisomic nuclei in 0.061% remained in CR. When two probes were used
      simultaneously in a sample from one patient, 1% of the residual cells were
      abnormal. The patient later suffered relapse. In one patient with anaplastic
      large cell lymphoma, CD30-positive interphase cells were shown to have trisomic
      chromosome 7 by immunophenotyping and FISH. Our results suggest that metaphase
      FISH using WCP probes is a sensitive and specific method for detecting minimal
      residual disease especially in patients with translocations.

PMID- 8152256
TI  - Reversal of CAMAL-mediated alterations of normal and leukemic in vitro
      myelopoiesis using inhibitors of proteolytic activity.
AB  - CAMAL (common antigen of myelogenous acute leukemia) is an antigenic preparation
      isolated in this laboratory from the bone marrow or peripheral blood leucocytes
      of persons with myeloid leukemias. Material from CAMAL preparations, which
      migrates in the range of 30 to 35 kDa by sodium dodecyl sulfate polyacrylamide
      gel electrophoresis (SDS-PAGE, P30-35 CAMAL), was shown to exert an inhibitory
      effect on in vitro colony formation by progenitor cells from normal healthy
      donors. The same preparations of P30-35 CAMAL, in contrast, exerted a stimulatory
      effect on in vitro colony formation by progenitor cells from patients with
      chronic myelogenous leukemia (CML). We now report that both the inhibitory effect
      on normal colony formation and the stimulatory effect on CML colony formation
      mediated by P30-35 CAMAL were blocked using phenyl methyl sulfonyl fluoride
      (PMSF), an inhibitor of the activity of serine proteases. Similarly, both the P30
      35 CAMAL-mediated inhibitory effect on normal colony formation and the P30-35
      CAMAL-mediated stimulatory effect on CML colony formation were blocked using the
      peptide ala-pro-phe-CMK, also an inhibitor of serine protease activity. These
      results suggest the involvement of proteolytic activity, either directly or
      indirectly, in the alterations of in vitro myelopoiesis exerted by P30-35 CAMAL.

PMID- 8152257
TI  - Biological consequences of p160v-abl protein tyrosine kinase activity in a
      primitive, multipotent haemopoietic cell line.
AB  - A temperature sensitive abl protein tyrosine kinase gene was transferred into a
      multipotent haemopoietic stem cell line, and the primary biological effects of
      expression of the gene were examined at the permissive and non-permissive
      temperatures. Unlike previous studies in factor-dependent cell lines, we found
      that expression of the functional abl protein tyrosine kinase did not lead to
      growth autonomy. Furthermore, the cells were still able to undergo terminal
      myeloid differentiation. However, expression of the functional gene did lead to a
      delay in maturation with a concomitant increase in cell production, had a modest
      effect in terms of delayed apoptosis particularly when the cells were maintained
      at a high cell density, and slightly increased the response to sub-optimal
      concentrations of IL-3. In many respects, therefore, the effects of abl protein
      tyrosine kinase in these cells mimics the effect of bcr/abl in primary
      haemopoietic cells where growth factor independence and an aberrant
      differentiation profile are relatively late events in clonal evolution and are
      not intermediate consequences of activation of the abl gene.

PMID- 8152258
TI  - Variability of the alloreactive T-cell response to human leukemic blasts.
AB  - Clinical and experimental data suggest a role for the immune response in
      preventing leukemic relapses after allogeneic bone marrow transplantation (BMT):
      the graft-versus-leukemia (GVL) effect. In this report, we have evaluated the
      response of normal donor lymphocytes against allogeneic leukemic cells as an in
      vitro model of the GVL effect. We used a limiting dilution technique in order to
      determine the frequency of cytotoxic T-lymphocyte precursors (pre-CTL) against
      allogeneic leukemic blasts among normal donor lymphocytes. We demonstrate a
      considerable variability of CTL precursor frequency. This variability depended on
      leukemic populations since, for a given leukemia, the pre-CTL frequency was
      comparable among our tested normal allogeneic donors. Moreover, when HLA-DR
      negative leukemias were used as allostimulators, the pre-CTL frequencies were
      extremely low. In order to verify the impact of leukemic DR expression on the
      stimulatory capacity of leukemic cells, we selected and analyzed in mixed
      lymphocyte tumor cell culture (MLTC), a panel of myelogenous and lymphoblastic
      leukemias with variable levels of DR expression, each against different
      allogeneic responders. Our results demonstrated a close correlation (r = 0.953, p
      < 0.0001) between the proliferative response of alloactivated lymphocytes and the
      percentage of stimulatory leukemic cells expressing HLA-DR molecules. Anti-MHC
      class II monoclonal antibodies inhibited the lymphocyte proliferation in the
      MLTC, confirming the preponderant role of DR in the generation of this response.
      Overall, our results demonstrate the extreme variability of leukemic cells in
      their allostimulatory capacity and the central role of DR expression in
      determining leukemic allo-recognition. In the setting of a clinical protocol, our
      data suggest that the infusion of allogeneic T lymphocytes in a DR negative
      leukemia will not lead to an alloreactive T-cell anti-tumor effect.

PMID- 8152259
TI  - Neutralizing antibodies during treatment of homologous nonglycosylated IL-3 in
      rhesus monkeys.
AB  - During administration of homologous nonglycosylated IL-3 to rhesus monkeys,
      reversal of hematologic effects and disappearance of side effects suggested a
      neutralizing anti-IL-3 antibody response. Among a total of 20 monkeys treated
      with IL-3, ELISA of serial serum samples revealed anti-IL-3 antibodies in ten
      animals. Antibody production tended to be dose dependent. Triplicate subcutaneous
      injections and i.v. administration provoked earlier appearance of antibodies than
      single s.c. injection. Prolonged continuous intravenous IL-3 administration (63
      and 93 days) at a dose of 1 microgram/kg/day did not result in antibody
      production. Among a total of eight animals with sufficiently high titers to allow
      for antibody purification, seven appeared to have generated antibodies that
      neutralized the biologic activity of IL-3 in vitro. In six monkeys, the response
      to IL-3 decreased while antibody titers rose, strongly suggesting neutralization
      of IL-3 in vivo. It is concluded that recombinant, nonglycosylated IL-3 as used
      in this study may elicit a neutralizing antibody response.

PMID- 8152260
TI  - Characterization of a human cell line (NK-92) with phenotypical and functional
      characteristics of activated natural killer cells.
AB  - The cell line described here was established for a 50-year-old male patient with
      rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated
      with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and
      peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3.
      Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T)
      cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To
      establish the line, cells from the peripheral blood were placed into enriched
      alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta
      mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is
      dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is
      sufficient to maintain proliferation. Conversely, cells die within 72 h when
      deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7
      induces short-term proliferation measured by 3H-thymidine incorporation. None of
      the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma)
      supported growth of NK-92 cells which have the following characteristics: surface
      marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker
      negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34,
      HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and
      gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when
      tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2
      concentration. The p75 IL-2 receptor is expressed on about half of the cells at
      low density irrespective of the IL-2 concentration. NK-92 cells kill both K562
      and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86%
      respectively, at an E:T cell ratio of 5:1). The cell line described here thus
      displays characteristics of activated NK-cells and could be a valuable tool to
      study their biology.

PMID- 8152261
TI  - Characterization of a myeloperoxidase mRNA(+) acute lymphoblastic leukemia cell
      line (EU-1/ALL) established from a child with an apparent case of ALL.
AB  - A myeloid-antigen-positive acute lymphoblastic leukemia (My+ALL) cell line (EU-1)
      was established from the bone marrow cells of a child with apparent ALL. By
      morphology, cytochemistry and fluorescent-antibody phenotyping, EU-1 cells
      appeared to be lymphoblastic (L1 morphology, TdT+, CD10+, CD19+). However, by a
      sensitive immunocytochemical assay, EU-1 cells additionally displayed several
      myeloid antigens (CD13, CD14, CD33) not detected by flow-cytometry. Furthermore,
      EU-1 cells were cytochemically and immunocytochemically negative for
      myeloperoxidase (MPO) but positive for MPO mRNA by Northern blot analysis. After
      incubation with dimethylsulfoxide (DMSO), myeloid cell surface antigens were
      detected on EU-1 cells by flow cytometry, and a marked decrease in MPO mRNA
      expression was observed. These results demonstrate that EU-1 is a unique ALL cell
      line representing a significant subset of pediatric ALL patients who also express
      myeloid antigens and have poor prognosis.

PMID- 8152262
TI  - Adult Philadelphia-chromosome-positive acute lymphoblastic leukemia: experience
      of treatments during a ten-year period.
AB  - Adult Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph1-positive
      ALL) represents about 30% of all adult ALL, and is considered a poor prognosis
      disease, since complete remission (CR), which can be achieved in 50-70% of cases,
      is usually short in patients treated with conventional chemotherapy. Presently
      bone marrow transplantation, performed early in first CR is becoming the
      treatment of choice, as it has shown to be able to cure some cases. In a ten-year
      period, at our department, among 108 adult ALL patients, in which cytogenetics
      was successfully carried out at diagnosis, 24 (22%) resulted Ph1-positive.
      Molecular biology was performed in 13 out of these 24 patients: 10 patients
      showed a p210 rearrangement and three p190. All patients have been treated at
      induction with conventional drugs, with a CR rate of 96%. As post-remission
      therapy, the first 17 cases (group 1) followed a chemotherapeutic program, like
      the other adult ALL; while the remaining six patients (group 2) have been
      enrolled in a pilot study including early BM transplantation. In group 1, the
      median overall duration of first CR is 7 months; 50% of relapses were recorded
      within the first 6 months, although in this group five patients exhibited a first
      CR prolonged more than 30 months. In group 2, among the six patients, three were
      submitted to allogeneic bone marrow transplantation (BMT), and three to
      autologous bone marrow transplantation (ABMT). Overall median duration of first
      CR is 13 months. Three patients relapsed, three are in continuous CR for 11, 31
      and 32 months.

PMID- 8152263
TI  - Potential strategies for circumventing myeloperoxidase-catalyzed degradation of
      vinca alkaloids.
AB  - Myeloperoxidase (MPO) has recently been shown in an in vitro, cell-free system to
      catalyze the peroxidative degradation of vincristine (VCR). Oxidation of VCR
      involves a ring fission between positions 20' and 21', and is thought to be
      facilitated by the presence of an hydroxyl (-OH) group at position 20'. We report
      here two different approaches, both with potential clinical application, to
      decrease MPO-catalyzed vinca degradation. Firstly, we tested the hypothesis that 
      OH substitution at position 20' increases vinca susceptibility to peroxidation by
      comparing the relative extent of degradation of vinorelbine (Navelbine or NVB),
      which lacks a 20' hydroxyl substitution, with that of VCR. As anticipated, NVB
      was significantly less susceptible to MPO-catalyzed peroxidation than was VCR (p
      < 0.01). Secondly, we screened an array of compounds that are in current clinical
      use for their ability to inhibit MPO. Acetaminophen, N-acetylcysteine,
      propylthiouracil, D-penicillamine, mefenamic acid, dapsone, and methimazole all
      inhibited MPO at clinically achievable concentrations. Insofar as increased MPO
      activity has been observed in patients with acute myeloid leukemia, these
      findings suggest potential strategies for improving the activity of vinca
      alkaloids in this disease.

PMID- 8152264
TI  - Detection of membrane and intracellular antigens by flow cytometry following
      ORTHO PermeaFix fixation.
AB  - In the present study, we explored the suitability of a new cell fixative (ORTHO
      PermeaFix, OPF) for the detection by flow cytometry of intracellular molecules
      while preserving the cell surface immunoreactivity, scatter features and
      morphology. The effect of OPF was investigated on whole blood of ten normal
      donors, and on separated blasts of 17 leukemic patients. OPF fixation for 45 min
      to 24 h maintained the morphology of lymphoid cells with minimal cellular
      distortion and scatter changes, and only slightly modified cell surface
      immunoreactivity. For at least 1 week following fixation, the cells were still
      suitable for immunostaining with monoclonal antibodies that recognize the main
      lymphoid populations. These included CD3, CD4 and CD8 for T-cell subsets, CD19
      and CD16 for B lymphocytes and NK cells, and CD45 for leukocyte common antigen
      (LCA). The OPF fixation of leukemic cells allowed the simultaneous detection of
      nuclear TdT in conjunction with membrane CD19, and with membrane and/or
      cytoplasmic CD22 in common-ALL, as well as with cytoplasmic CD3 in T-ALL cases.
      Our findings suggest that with the introduction of this new fixative into the
      routine laboratory service, a number of convenient and practical arrangements can
      be made which increase the efficiency of immunodiagnosis. Small laboratories with
      no inhouse flow-cytometric facilities can now accumulate OPF-treated whole blood
      samples for at least 3-4 days and send these to reference laboratories. In
      addition, the immunodiagnosis of acute leukemia is greatly facilitated by
      combination staining for membrane and intracellular antigens both at diagnosis
      and when the analysis of minority populations is warranted for detecting minimal
      disease.

PMID- 8152265
TI  - Non-dysplastic myelodysplasia?
AB  - Patients successfully treated for a malignancy with cytotoxic therapy have an
      increased risk of developing secondary myelodysplasia (MDS) and acute myeloid
      leukemia (AML). We report a patient in remission from Hodgkin's disease (HD) who
      remains hematologically normal 4 years after combination chemotherapy, but who
      has biological and genetic abnormalities characteristic of myelodysplasia. X
      inactivation analysis using a 5' phosphoglycerate kinase (PGK) probe demonstrates
      polyclonal hematopoiesis, but cytogenetic analysis reveals a clonal population
      with a minority of metaphases having a 7q-deletion. NRAS mutations are not
      detectable 1 year after treatment, but are present in two separate clones (at
      codons 12 and 15) analyzed by single-stranded conformational polymorphism (SSCP),
      followed by cloning and sequencing 4 years after treatment. The presence of an
      activated NRAS with the same codon 12 mutation was independently confirmed by the
      nude mouse tumorigenicity assay. In vitro peripheral blood granulocyte-macrophage
      colony-forming units (CFU-GM) have changed from normal to undetectable levels
      while erythroid burst forming units (BFU-E) were significantly reduced on two
      occasions during the period of observation. These abnormalities are
      characteristic of MDS. Continued clinical follow-up will determine whether these
      evolving genetic and biological abnormalities pre-date the onset of clinical and
      morphological features of MDS.

PMID- 8152266
TI  - Transient adult T-cell leukemia/lymphoma picture during varicella infection in an
      HTLV-1 carrier.
AB  - HTLV-1 (human T-lymphotropic virus type 1) is associated with tropical spastic
      paraparesis, adult T-cell lymphoma (ATL), and also with opportunistic infections.
      The risk for developing ATL in HTLV-1 healthy carriers is low, between 1 and 4%.
      Nothing is known about the events promoting the evolution from the healthy
      carrier state to symptomatic ATL. We describe the case of a 44-year-old French
      Caribbean man with a chronic and recurrent strongyloidiasis in which the
      occurrence of a hemorrhagic and necrotic varicella led to the discovery of an
      infection by HTLV-1 and an acute form of ATL. All hematological data were normal
      before the onset of varicella. ATL completely disappeared at the same time as the
      varicella healed. This leads us to hypothesize that acute infections such as the
      reactivation of varicella-zoster may act as a promoting factor for the
      development of ATL in healthy HTLV-1 carriers.

PMID- 8152268
TI  - Retroviruses and cancer: US-Japan clinico-epidemiological experiences held under
      the auspices of the US-Japan bilateral agreement.

PMID- 8152267
TI  - A 62-kilodalton tyrosine phosphoprotein constitutively present in primary chronic
      phase chronic myelogenous leukemia enriched lineage negative blast populations.
AB  - Ph+ chronic myelogenous leukemia (CML) is associated with the reciprocal
      translocation between chromosomes 9 and 22 culminating in the production of the
      chimeric p210bcr/abl protein possessing elevated protein tyrosine kinase activity
      relative to the normal c-abl tyrosine kinase. Our recent studies have revealed
      subtle differences in the growth, phenotypic and morphologic characteristics of
      subpopulations of primary lin- Ph+ chronic phase CML blasts and comparable
      primary normal blasts. In an attempt to correlate these biologic abnormalities
      and the presence of the p210bcr/abl protein, we initiated studies to identify
      differences in proteins constitutively phosphorylated on tyrosine in whole cell
      lysates of comparable primary early blast subpopulations derived from normal and
      Ph+ chronic phase CML marrows. Immunoblotting with anti-P-tyr Abs demonstrated a
      prominent 62 kDa phosphotyrosyl protein (pp62) constitutively present in 11/11
      Ph+ chronic phase linblasts while being virtually undetectable in equivalent
      amounts of protein derived from 15/15 and 2/2 comparable normal and Ph-negative
      chronic phase blast populations, respectively. Immunoblotting with an Ab
      reportedly specific for the ras GTPase activating protein (GAP) associated p62
      protein revealed that the pp62 present in CML blasts is not immunologically
      related to the former protein. Although the identity of the pp62 is presently not
      known, its prominent presence in chronic phase CML blasts, in which the only
      known molecular abnormality is putatively the p210bcr/abl protein, strongly
      suggests that it may be a critical p210bcr/abl substrate involved in an early
      stage of expansion of the Ph+ clone.

PMID- 8152269
TI  - Clonal evolution in a transforming 5q- syndrome.

PMID- 8152270
TI  - Value of routine bone marrow aspirates for surveillance of remission in acute
      leukemia.

PMID- 8152271
TI  - Myelodysplastic syndrome evolving into a myeloproliferative disorder: one disease
      or two?

PMID- 8152272
TI  - 1993 Robert R. deVilliers Lecture. Chromosome translocations: dangerous liaisons.
AB  - Rearrangements involving chromosome band 11q23 are very common in acute leukemia,
      both lymphoblastic and myeloid (monoblastic), and are less common in lymphoma.
      Although several different genes have been cloned from 11q23 translocation
      breakpoints, the great majority involve the MLL (myeloid-lymphoid leukemia) gene.
      The MLL gene has several different names, ALL1, Htrx, HRX; the central part of
      the gene codes for multiple zinc fingers which show strong homology to the
      Drosophila trithorax gene. MLL is involved in four common translocations as well
      as in 25 uncommon or rare translocations, insertions and deletions. The
      translocation breakpoints occur within an 8.3kb region which can be detected with
      a 0.7 kb cDNA probe. Twenty-five percent of patients have a deletion 3' of the
      breakpoint which includes the zinc finger region. Patients who previously
      received drugs that inhibit topoisomerase II often develop acute leukemia with
      translocations involving 11q23. These translocations break MLL in the same 8.3kb
      region. In the four breakpoints cloned to date, the translocation has led to a
      fusion gene on the derivative 11 chromosome with a chimeric transcript,
      consisting of 5' MLL and the 3' segment of the other gene. Although transcripts
      were also cloned from the other derivative chromosome, all the evidence indicates
      that the critical fusion gene is on the derivative 11 chromosome. The molecular
      dissection of these rearrangements will provide insights into the biology of MLL
      and into the interaction of MLL with topoisomerase II inhibitors. In addition,
      this research has provided DNA probes that will be important for diagnosis and
      for monitoring patients during the course of their disease.

PMID- 8152274
TI  - Erythropoietin receptor and interleukin-2 receptor use different downstream
      signaling pathways for proliferation and apoptosis-block.
AB  - Erythropoietin (EPO) regulates proliferation and differentiation and prevents
      apoptosis of erythroid progenitor cells by binding to erythropoietin receptor
      (EPOR) expressed on the surface of those cells. The mechanism by which EPO signal
      is transmitted to the cells through EPOR is still unclear. In the present study,
      we introduced and expressed EPOR in an interleukin-3 (IL-3) dependent pro-B cell
      line, BAF-B03 and an interleukin-2 (IL-2)-dependent cytotoxic T cell line, CTLL-2
      and analyzed their growth response to EPO and the DNA breakdown characteristic to
      apoptosis after deprivation of the growth factor. BAF-B03-derived cells
      expressing EPOR proliferated in response to EPO but CTLL-2-derived cells
      expressing EPOR (C/EPOR) did not. DNA from C/EPOR cells cultured in the absence
      of IL-2 with or without EPO had similar patterns of DNA breakdown. These results
      suggest that downstream signaling pathways for the cell proliferation and
      apoptosis-block are, at least, partially different between EPOR and IL-2 receptor
      (IL-2R).

PMID- 8152273
TI  - Chlorambucil induced apoptosis in chronic lymphocytic leukemia (CLL) and its
      relationship to clinical efficacy.
AB  - Chlorambucil induced apoptosis was measured in CLL cells treated with clinically
      achievable drug doses in vitro. While spontaneous apoptosis occurred in CLL cells
      incubated in vitro in the absence of drug, the level of apoptosis, as measured by
      the extent of DNA fragmentation, was greater in cells treated with chlorambucil.
      In addition, macrophages were shown to engulf drug treated CLL cells in vitro. To
      determine if chlorambucil can also induce apoptosis in vivo, CLL cells were
      isolated from patients before treatment and at intervals after clinical therapy
      with chlorambucil (0.9 mg/kg given over 3 days). Apoptosis was measured in these
      cells immediately after isolation and following incubation in vitro for 72 hr. No
      apoptotic changes were detected in cells immediately after isolation either
      before or after clinical treatment. In contrast, apoptosis was observed in cells
      that were incubated ex vivo for 72 hr, and the level of apoptosis was greater in
      cells that were isolated after chlorambucil treatment compared with cells
      obtained prior to therapy. The increased apoptosis observed in CLL cells ex vivo
      after therapy was related to the fall in the patient's lymphocyte count. In
      general, a large increase in apoptosis ex vivo after treatment was followed by a
      significant decrease in the patient's lymphocyte count. Thus, chlorambucil may
      produce its antitumor effect in CLL by inducing apoptosis-associated membrane
      changes that result in rapid clearance of the apoptotic cells by the immune
      system.

PMID- 8152275
TI  - An enhanced surveillance program for adult T-cell leukemia in central Brooklyn.
AB  - The Brooklyn Adult T-cell Leukemia/Lymphoma (ATL) study was developed to estimate
      the incidence of the human T-cell lymphotropic virus type I (HTLV-I)-associated
      ATL in the Crown Heights/Bedford Stuyvesant community. This central Brooklyn
      black community is an area which has already been shown in earlier reports to be
      endemic for HTLV-I-associated ATL. Surveillance has been conducted at seven area
      hospitals that serve this community, with surveillance already completed at five
      hospitals. Potential study subjects who are 20 years or older are identified by
      the review of admission records, discharge summaries, pathology and clinical
      chemistry reports, or physician referrals. Diagnoses of leukemia or lymphoma, or
      the presence of leukocytosis or hypercalcemia are used as criteria to identify
      the subjects. Participating subjects give a sample of blood for the determination
      of HTLV-I infection by serologic tests. At the time of enrollment, subjects
      provide demographic information including age, sex and birthplace. After one year
      of surveillance at five hospitals (39.5% of inpatient beds in the catchment), we
      have identified 12 cases of HTLV-I-associated ATL. The mean age of the ATL
      patients was 50 years, with patients being predominantly female (83.3%) and often
      Caribbean immigrants (83.3%). Interestingly, 42% of our cases were identified
      solely by findings of hypercalcemia from clinical chemistry reports. The
      remaining ATL cases were identified by physician referral. This enhanced
      surveillance program that uses both clinical and laboratory criteria for ATL case
      ascertainment can serve as a prototype for similar surveillance in other areas
      endemic for HTLV-I-associated ATL--an important effort because of the strong
      potential for disease prevention.

PMID- 8152276
TI  - Molecular diagnosis and monitoring of acute promyelocytic leukemia treated with
      retinoic acid.
AB  - The characteristic balanced 15;17 translocation, t(15;17), of acute promyelocytic
      leukemia (APL) fuses the retinoic acid receptor alpha (RAR alpha) gene on
      chromosome 17 to PML, a recently described gene of unknown function, on
      chromosome 15. It is this fusion gene and consequent fusion protein that is
      thought to be responsible for both the block in normal myelocyte differentiation
      as well as the dramatic in vitro and in vivo response to the differentiating
      effects of all-trans retinoic acid (RA). The t(15;17) also provides a genetic
      marker for the presence of leukemic cells. PML/RAR alpha fusion mRNA's can be
      detected by a reverse transcription polymerase chain reaction (RT-PCR) assay.
      Using this assay, at least three distinct patterns, differing in the 3' region of
      the PML breakpoint, can be identified. The detection of abnormal mRNA's by the RT
      PCR assay has proven to be an important aid in the diagnosis of APL as well as
      the best predictor of an initial clinical response to RA. The results of an
      ongoing, longitudinal evaluation of patients with APL show that the RT-PCR assay
      may also be a useful indicator of minimal residual disease (MRD). Negative RT-PCR
      assays following completion of all therapy are associated with prolonged disease
      free survival, whereas persistence or return of a positive test is highly
      correlated with subsequent relapse. Further studies will determine whether
      patients who test positive may benefit from the introduction of additional
      antileukemic therapy.

PMID- 8152277
TI  - Transcription of HERV-K-related LTRs in human placenta and leukemic cells.
AB  - The human genome contains a family of endogenous retroviruses, HERV-K, with
      sequence homology to the B-type mouse mammary tumor virus (MMTV). We have
      detected HERV-K-LTR related cDNA clones by screening a human placenta cDNA
      library with a HERV-K LTR probe. Three of the isolated cDNA clones were
      characterized by nucleotide sequencing. The analyzed clones did not contain any
      retroviral sequences other than those related to HERV-K LTRs, but were found to
      be coexpressed with cellular sequences. Furthermore, transcripts containing HERV
      K LTR sequences were demonstrated by Northern blotting and PCR in human leukemic
      and normal white blood cells, as well as in various tumor cell lines, indicating
      abundant transcription of solitary HERV-K LTRs in human tissues. In patients with
      lymphatic leukemias, a transcript of about 6 kb hybridizing with HERV-K LTR was
      detected that was not found in patients with myelogenous leukemias or in healthy
      persons.

PMID- 8152278
TI  - Adoptive immunotherapy with activated peripheral blood lymphocytes.
AB  - Adoptive immunotherapy is used to treat malignant tumors resistant to
      conventional therapeutic modalities. Patients with metastatic melanoma, renal
      cell carcinoma or mesothelioma are most likely to benefit from this treatment.
      Tumor infiltrating lymphocytes (TIL) contain tumor specific killer cells and are
      found to be the most effective. When TIL is not available or until it can be
      produced in sufficient amount, autologous activated lymphocytes (AAL) are an
      alternative. AAL are leukapheresed lymphocytes, activated by conditioned medium
      from OKT3 stimulated autologous lymphocytes. Subcutaneous IL-2 and oral
      cimetidine are also administered to support the reinfused AAL and to inhibit
      activation of CD8+ suppressor cells, respectively. To improve the yield and
      activation of reinfused lymphocytes, addition of IL-2 to the culture medium was
      tested in different time intervals after the onset of the culture. Interleukin-2
      added in the first or second day i) improved the yield of activated lymphocytes;
      ii) increased the expression of activation markers CD25 (IL-2 receptor) and HLA
      DR and iii) augmented killing of tumor cells. Later addition of IL-2 had no or
      negative effects. In vitro priming of peripheral blood mononuclear cells with
      autologous or allogeneic but histologically identical tumors was used to increase
      tumor-specificity of AAL. Autologous serum, containing antibodies specific to
      tumor cells, facilitated antigen presentation and yielded cytotoxic lymphocytes
      capable of efficiently killing tumor cells.

PMID- 8152280
TI  - Donor leukemia following allogeneic bone marrow transplantation.
AB  - Although allogeneic bone marrow transplantation has been shown to be a highly
      effective treatment for acute and chronic leukemia, leukemic relapse remains a
      significant problem. Leukemic relapse occurs in recipient cells in the majority
      of cases, but the paucity of donor cell leukemias may reflect the sensitivity of
      the investigative technique. We have developed a highly sensitive technique to
      identify the origin of all hematopoietic cells in the post transplant state which
      is based on PCR amplification of microsatellites, polymorphic tandem repetitive
      elements. We have identified donor leukemia (AML M5) following a sex matched BMT
      for severe aplastic anemia, verified a previously reported case of donor leukemia
      following BMT for chronic granulocytic leukemia and recently identified an
      acquired cytogenetic abnormality(del 11q23) in donor cells four years following
      an apparently successful BMT for AML. In all cases the donors have remained
      healthy. Postulated mechanisms include transfer to the transplanted marrow of a
      dormant oncogene residing in the DNA of either a virus, the chromosomes of
      degenerating irradiation damaged host leukemic cells or in the marrow stroma
      which is radioresistant and host in origin following BMT. Using sensitive
      techniques donor leukemia has been shown to be a more common event than was
      previously thought and an understanding of its pathogenesis may allow us to
      elucidate leukemogenic mechanisms in man.

PMID- 8152279
TI  - Therapeutic progress and comparative aspects in chronic myelogenous leukemia
      (CML): interferon alpha vs. hydroxyurea vs. busulfan and expression of MMTV
      related endogenous retroviral sequences in CML. German CML Study Group.
AB  - In summary, it can be expected that the availability of unrelated donors will
      increase the number of CML patients that can be treated curatively with
      allogeneic BMT. Hydroxyurea has replaced busulfan as first line treatment in CML
      since it prolongs survival. Ongoing randomized studies comparing IFN-based
      treatment regimens with standard chemotherapy or IFN-monotherapy probably will
      answer the question whether IFN can cure a small percentage of CML patients and
      whether this small percentage can be increased by additional chemotherapy. The
      present attempts to improve prognostic scores and to apply them to early
      treatment decisions will allow treatment adaptation more individually. The
      implications of endogenous retroviral sequences expressed in CML cells are not
      known now, but may be far reaching.

PMID- 8152281
TI  - Polyclonal hemopoiesis in leukemia patients following molecularly documented
      remission.
AB  - We performed clonality studies of hemopoietic reconstitution in 24 female
      patients (pts) with leukemias characterized by specific tumor markers. Thirteen
      pts had Acute Promyelocytic Leukemia (APL) with rearrangements of the RAR-a and
      PML genes, 8 BCR rearranged (BCR+)/Ph+ Chronic Myeloid Leukemia (CML) and 3
      BCR+/Ph+ Acute Lymphoid Leukemia (ALL). Bone marrow (BM) DNA samples were
      obtained at diagnosis and at remission after Southern blot documented suppression
      of specific markers. The clonal or non-clonal nature of hemopoietic
      reconstitution was assessed by hybridizing the same DNAs with the M27 beta probe,
      in order to detect methylation differences at the X-linked DXS255 locus. Twenty
      four pts showed a polyclonal methylation pattern at remission, whereas in 3 cases
      an apparently clonal pattern was observed despite no evidence of specific gene
      rearrangement. In 2 of these 3 cases, however, DNAs derived from non-affected
      tissues (T lymphocytes, skin and BM fibroblasts) revealed the presence of the
      same DXS255 unmethylated allele detected at diagnosis, while in the third case we
      found the same apparently clonal pattern in blood mononuclear cells obtained from
      her healthy female BM donor. These data indicate that polyclonal hematopoiesis
      occur in APL and CML pts after therapy induced suppression of specific tumor
      markers, and that unbalanced or aberrant X chromosome methylation patterns are
      observed in some cases, most likely reflecting constitutional features.

PMID- 8152282
TI  - Combination therapy with nucleoside analogs and alkylating agents.
AB  - The nucleoside analog, 2'-deoxycoformycin (dCF), and the alkylating agents,
      chlorambucil (CLB) and cyclophosphamide, are effective agents in the treatment of
      chronic B cell leukemias and lymphomas. The cyclophosphamide analog, 4
      hydroperoxycyclophosphamide (4-HC), generates the same active metabolite as
      cyclophosphamide in cells and has been used extensively for bone marrow purging
      in vitro. We have observed that deoxyadenosine (dAdo) plus dCF (dAdo/dCF) inhibit
      the repair of x-irradiation-induced and bleomycin-induced DNA damage in vitro,
      and that this results in either synergistic or additive cytotoxicity,
      respectively. In the present study we examined whether dAdo/dCF, can enhance the
      antitumor activity of CLB and 4-HC in chronic lymphocytic leukemia (CLL) cells in
      vitro. CLL cells were treated with CLB for 6 hr and then with dAdo/dCF for 18 hr
      and cytotoxicity was measured by the MTT assay. Synergy was observed between CLB
      and dAdo/dCF in CLL cells from 2 patients, with synergy increasing as the CLB
      dose was raised. In contrast, similar treatment of human bone marrow cells
      resulted in little or no synergistic cell kill. Treatment of CLL cells from 2
      patients with 4-HC for 30 min followed by dAdo/dCF for 18 hr resulted in little
      synergistic cytotoxicity, although this drug combination did produce an additive
      cell kill. Thus, combination therapy with nucleoside analogs and alkylating
      agents may be useful for improving treatment of CLL.

PMID- 8152283
TI  - Gene transplantation: combined antisense inhibition and gene replacement
      strategies.
AB  - Optimal gene replacement protocols would include both inhibition of the
      endogenous gene and overexpression of the preferred (or mutant) gene. We have
      developed a novel gene transfer method to test whether antisense-resistant genes
      (designed by deletion of antisense RNA target sequences) can replace the function
      of endogenous genes. Immunoprecipitation studies demonstrated that inducible anti
      fos RNA (antisense directed against the c-fos gene) reduces endogenous c-fos
      expression by 90%, but did not affect the transfected antisense-resistant mutant
      c-fos genes. Cell growth studies demonstrated that full-length and minimally
      truncated c-fos expression vectors could restore serum-induced DNA synthesis but
      that C-terminally truncated Fos mutants including FBR v-fos could not.
      Transcriptional studies demonstrate that the endogenous c-fos protein contributes
      to AP-1 activity and normally suppresses regulated SRE (serum response element)
      activity. This "gene transplant" method for inhibition of endogenous genes and
      replacement with preferred genes has implications for gene therapy of hereditary
      hematologic disorders and for the correction or "repair" of oncogenes or tumor
      suppressor genes in leukemias and lymphomas.

PMID- 8152284
TI  - Mutational analysis of the HIV-1 Vpu protein.
AB  - The human immunodeficiency virus type-1 (HIV-1) encoded Vpu protein facilitates
      the release of budding virions from the surface of infected cells and delays the
      rate of syncytium formation of the virus. Furthermore, Vpu induces rapid
      degradation of nascent CD4 molecules that are retained in the endoplasmic
      reticulum by the formation of gp160-CD4 complexes. Currently, little is known of
      the precise mechanism(s) by which Vpu function. Whether or not these different
      events are related remain unclear. In this report, we describe our recent
      structure/function studies on vpu suggesting that the protein may have
      independent biological activities during the HIV-1 infection.

PMID- 8152285
TI  - Neonatal HIV-1 thymic infection.
AB  - The thymus is the primary site of T cell ontogeny and selection during fetal and
      neonatal development. Previous studies have established that the thymus is also a
      site of HIV-1 infection, as early as the first trimester of pregnancy. Alteration
      of the thymocyte maturation process by HIV-1 could impact on the peripheral T
      cell population and interfere with immune responses. A neonatal thymic organ
      culture system was established to study HIV-1 infection within the thymus. We
      have shown that this primary tissue isolate can support a productive HIV-1
      infection. Infection occurred without detectable thymocyte cytopathology. The
      ability to infect the developing thymocyte within an intact micro environment
      will enable us to further establish the kinetics of acute HIV-1 thymic infection
      and its consequences on lymphocyte maturation.

PMID- 8152287
TI  - Long-term persistence of AZT-resistance mutations in the plasma HIV-1 of patients
      removed from AZT therapy.
AB  - Zidovudine (3'-azido-2',3'-dideoxythymidine) resistant isolates of human
      immunodeficiency virus type I (HIV-1) were previously demonstrated in zidovudine
      treated AIDS patients. The genetic linkage of multiple mutations characteristic
      of zidovudine-resistance as well as dideoxyinosine-resistance were demonstrated
      by examining clones of viral reverse transcriptase after polymerase chain
      reaction (PCR) amplification of plasma culture DNA. The zidovudine-resistance
      mutations persisted in seven timepoints from four patients for 5 to 22 months
      despite cessation of zidovudine therapy (and while patients underwent ddI
      therapy). One patient's plasma virus isolate at 14 months possessed a genotype
      doubly resistant to ZDV and ddI. Virus recovered from four timepoints showed
      Intermediate to high levels of zidovudine-resistance. As these genotypes were
      mainly derived from plasma culture, the zidovudine resistant virus appears to
      persist and replicate well in vivo after cessation of zidovudine therapy.

PMID- 8152286
TI  - Virus induction of NF-kappa B/Rel proteins and type I interferon gene expression
      in myelomonoblastic cells.
AB  - The correlation between virus induced NF-kappa B DNA binding activity and
      interferon gene expression was examined in the myelomonoblastic PLB-985 cell
      line. Previous studies have shown that chronic HIV-1 infection of PLB-985 cells
      (PLB-IIIB) leads to the selection of cells with a more differentiated monocytic
      phenotype and with constitutive NF-kappa B DNA-binding activity. In this report
      we demonstrate that the kinetics of HIV-1 and Sendai virus infection of PLB-985
      cells directly correlates with induction of NF-kappa B DNA binding activity.
      Based on UV cross-linking and immunoprecipitation analysis, p50, the strong
      transcriptional activator p65 and c-Rel represent the major constituents of this
      NF-kappa B DNA-binding activity. We also demonstrate an alteration in the
      kinetics of type I IFN gene transcription following secondary Sendai virus
      infection of PLB-IIIB cells compared to PLB-985. The results of our studies
      suggest that HIV infected individuals may respond differently to secondary viral
      or bacterial infections by augmenting the synthesis of NF-kappa B regulated
      immune response modifiers, which could alter the onset or progression of AIDS.

PMID- 8152288
TI  - Different effects of breast cancer, HIV-1 infection and chemotherapy on inducible
      natural immunity.
AB  - Breast cancer chemotherapy and HIV-1 viral infection (AIDS) can result in
      respective transient or irreversible losses of up to 40-50% of circulating
      lymphocytes. The relationship of lymphopenia on tumor immunosurveillance and the
      control of opportunistic infections has yet to be established. The objective of
      this study was to characterize the changes in natural killer (NK) and lymphokine
      activated killer (LAK) cell function associated with cytotoxic drug therapy,
      breast cancer and HIV-1 infection. NK and LAK activities were measured at
      multiple effector to target ratios. Exponential regression analysis of target
      cell lysis determined the maximal % target kill and the lytic potential of
      effector cells. Flow cytometric analysis of lymphocyte subsets in seropositive
      populations was performed to determine the % of NK(CD56+) cells. Taken together,
      our findings indicate that cytotoxic NK pool sizes increased in breast cancer
      patients, diminish consequent to chemotherapy. The functional capacity of
      individual NK and LAK cells remains intact. In contrast, the diminution of NK and
      LAK functional responses in HIV-1 seropositive individuals is associated with
      reductions in cytotoxic NK and LAK pool sizes, as well as marked reductions in
      cytolytic function of individual cells. Zidovudine (AZT) treatment did not affect
      LAK activity in HIV+ subgroups. Our findings indicate that NK and activated LAK
      functions are affected both by chemotherapy and disease etiology.

PMID- 8152289
TI  - The membrane proximal segment of the IL-2 receptor beta-chain acidic region is
      essential for IL2-dependent protein tyrosine kinase activation.
AB  - The signal transduction mechanism of the interleukin-2 receptor (IL-2R) remains
      largely undefined. The cytosolic domain of the IL-2R beta subunit is known to be
      essential for coupling to intracellular signaling pathways such as protein
      tyrosine kinase (PTK) and for control of IL-2 dependent cellular proliferation. A
      panel of cell lines that express IL-2R beta chains that contain sequential
      truncation mutations within the cytosolic domain were constructed. These cell
      lines were used to map the interaction of IL-2R with PTK activation, and the
      linkage of PTK function to activation of the enzyme phosphatidylinositol-3-kinase
      (Pl3K). The data show that the amino terminal segment of the acidic region
      (residues 314-350) within IL-2R beta is a critical site for PTK activation, and
      that activation of Pl3K is linked to IL-2 dependent tyrosine phosphorylation.

PMID- 8152290
TI  - Suppression of retroviral tumors in hosts immune to viral oncogene product.
AB  - Feline sarcoma virus of Snyder-Theilen strain (ST-FeSV) induces sarcomas in
      Wistar/Ma rats following neonatal virus injection. Induced tumors express the
      viral oncogene product (P85) and elicit in hosts the specific serum anti-P85
      antibody detectable by Western blot analysis. Syngeneic adult female rats were
      immunized with an ST-FeSV induced sarcoma that was 100% transplantable to
      syngeneic adult rats. Newborns from immunized rats (vaccinated rats) were found
      to carry anti-P85 in their sera at birth. Following neonatal injection of the
      virus to vaccinated and non-vaccinated control rats, tumor incidence was found to
      be lower and survival time significantly longer in vaccinated rats than in
      controls (p < 0.01). A nonapeptide known to be thymic hormone (FTS) showed
      suppressive effects on tumor development. These results indicate that tumors
      caused by perinatal retrovirus infection may be suppressed by efficient
      elicitation of cell-mediated immune response against the product of oncogene of
      the causative virus.

PMID- 8152291
TI  - Human cancer vaccines.
AB  - Immune T cells recognize peptide antigens presented to them within self-MHC
      molecules. Thus auto-tumor reactive lymphocyte populations can be generated.
      Antigenic expression can be modified and intensified and reactive lymphocyte
      populations can be expanded. Active immunization of the tumor-bearing human host
      can induce immune reactions of tumor rejection strength. Frequently,
      micrometastases can be eliminated and occasionally partial or complete remissions
      of gross metastases can be induced.

PMID- 8152292
TI  - Lymphoma and pregnancy: clinical observations and experimental investigations.

PMID- 8152294
TI  - Phenotype analysis of lymphocytes present in different stages of neoplasia
      induced by bovine leukemia virus.
AB  - Distribution of subpopulations of lymphocytes in the lymph nodes and tumor
      tissues from cattle with enzootic bovine leukosis (EBL) was examined by
      immunohistology using a panel of monoclonal antibodies against leukocyte
      differentiation molecules of bovine leukocytes and tumor-associated antigen (TAA)
      of EBL. As disease progressed in the lymph nodes, TAA positive cells increased in
      number and were strongly positive. The number of B-B2, IgM positive cells were
      reduced in frequency in the follicle and areas of neoplastic cell-proliferation.
      Alpha beta and gamma delta T cells positive for WC1 (workshop cluster
      designation) were reduced in frequency due to infiltration and proliferation of
      neoplastic cells. In tumor tissues which were thought to consist with monoclonal
      population of cells carrying BLV provirus, strongly TAA-positive cells were
      present throughout the section. Most of the neoplastic cells from five cattle
      with EBL appeared to be divided into four types, CD2-, CD4-, CD8-, WC1-, B2+ or
      B2-, IgM+ or IgM-, MHC II+ and strong TAA+. WC1+ cells played no apparent role in
      the development of lymphosarcoma of EBL. WC1+ cells were not observed in tumor
      tissues. However, the possibility of effect of T cell for tumor immunity was
      suggested, since TH/l and Tc/s cells were scattered in the tumor tissues.

PMID- 8152293
TI  - Experimental model for MDS-like myelodysplasia in transgenic mice harboring the
      SV40 large-T antigen under an immunoglobulin enhancer.
AB  - The SV40 large T gene under the control of immunoglobulin enhancer induced
      hyperproliferation of multi-lineage hematopoiesis in transgenic mice. Hence the
      disease has been considered to be an appropriate experimental model for MDS-like
      myelodysplasia, sequential pathological changes in the development of the disease
      are introduced in the report. Huge splenomegaly was the major gross abnormality,
      which developed with 100% frequency; neither hepato-renal, nor other thymico
      lymphatic involvement was common. During the progressive increase in splenic
      weight, extensive proliferation of multi-lineage hemopoiesis was prominent,
      although no differences were apparent in the cellular proportions of each
      hematopoietic element compared with normal spleens, either in flow-cytometric
      analysis using markers for each subset of hematopoietic elements, or in the
      histological findings. In the later phases of the disease, the proliferating cell
      type tended to shift to a variety of single to oligo-lineage hemopoiesis, but the
      majority of mice still showed the presence of multi-lineage hemopoiesis;
      histologically, such hemopoiesis was somewhat dysplastic, but had no apparent
      nature of leukemic infiltration. Several transplantation-assays essentially
      supported the low neoplastic potential of proliferating cells even in later
      phase. A long-term observation was made aiming to induce more frequent transition
      of this abnormal hemopoiesis into a single-lineage neoplasm by transplantation of
      pre-onset spleen cells, as well as bone-marrow cells from transgenic mice at an
      early phase of the disease, into lethally irradiated C57BL/6 mice. This trial
      resulted in a variety of neoplastic growths in the recipients; not only was
      myelodysplastic hypercellularity seen, but also, single-lineage hemopoietic
      malignancies, such as B-cell lymphomas/leukemias, histiocytic malignancies, and
      even myeloid leukemias. The transition from multi-lineage myelodysplasia into
      single lineage hemopoiesis at some frequency is reminiscent of myelodysplastic
      syndromes (MDS) in humans. Higher frequency of transition into lymphoid
      malignancies may be due partly to the immunoglobulin enhancer used as a promoter
      unit. The results that the SV40 large T antigen was expressed in every
      proliferating cells, there was no apparent increase in multi-CSFs activity;
      together with the results of the transplantation assays suggest that the
      hyperproliferation of the cells is directly induced by the expression of SV40
      large T antigen in the hemopoietic cells themselves.

PMID- 8152295
TI  - Transcriptional regulation of ALV bursal lymphomagenesis.
AB  - Avian leukosis virus (ALV) induces bursal lymphoma in chickens after rare
      integration of proviral long terminal repeat (LTR) sequences next to the c-myc
      proto-oncogene. Labile LTR-binding proteins are essential for c-myc
      hyperexpression, since LTR-enhanced transcription, as well as the activity of the
      LTR-binding proteins, is specifically decreased following protein synthesis
      inhibition. This lability is restricted to hematopoetic cells of ALV-susceptible
      chicken strains, suggesting that the labile proteins play an important role in
      susceptibility to lymphomagenesis. Five proteins that interact with the ALV LTR
      enhancer were identified from bursal lymphoma cells: two proteins are stable (b
      and c), while three proteins (a1, a3, and b*) are labile in pre-B cell types. Two
      cDNAs (a1/EBP and a3/EBP) encoding leucine zipper proteins that bind to the ALV
      LTR enhancer were cloned using a lambda gt11 cDNA expression library made from
      bursal lymphoma cells. We are presently studying the roles of a1/EBP and a3/EBP
      in labile regulation of LTR-enhanced c-myc transcription and susceptibility to
      bursal lymphomagenesis.

PMID- 8152296
TI  - Properties of tumors arising in SCID mice injected with PBMC from EBV-positive
      donors.
AB  - Groups of SCID mice were injected with different PBMC sub-populations, and
      established LCL cells. In about 80% of PBMC-injected animals, tumors developed in
      association with high levels of human Ig in mouse serum and detectable IL-6
      levels. The tumors showed a histopathologic pattern reminiscent of large cell
      immunoblastic non-Hodgkin's lymphoma; in situ hybridization invariably evidenced
      EBV sequences in a minority of cells. Genotypic analysis of tumors arising in
      PBMC-injected mice showed the presence of different oligoclonal B cell
      populations in different tumor sites. Southern blot analysis disclosed the
      presence of both linear (replicating) and episomal (latent) EBV DNA forms;
      sequential analysis of LCL cells serially passaged into animals revealed the
      progressive selection of clonal cells with only the latent episomal form.
      Attempts to dissect the events underlying tumor development revealed that the
      presence of T cells within the injected population was essential for tumor
      generation; however, the putative T cell-derived factors involved are unclear,
      and IL-6 seems to play a minor role.

PMID- 8152297
TI  - Modulation of hematopoiesis by lymphocyte membrane-derived components.
AB  - Membrane bound erythroid burst-promoting activity (mBPA) is an integral membrane
      protein that is present on normal B-cells and some activated T-cells, that
      induces burst-forming units-erythroid (BFU-E) when cultured with human
      erythropoietin (rHuEpo). Plasma membranes and vesicles shed from the leukemic A-1
      cell line express mBPA. This activity derived from both A-1 cells and normal B
      cells can be immunoadsorbed by the D3A4 antibody raised against mBPA. In this
      study, we demonstrate that interferon-gamma (IFN-gamma) suppresses BFU-E
      proliferation when added directly to culture of normal human bone marrow cells
      and in the absence and presence of A-1 cells. However, FACS analysis reveals that
      IFN-gamma enhances the surface expression of mBPA on A-1 cells. The role of IFN
      gamma in modulating erythropoiesis in vitro is discussed with respect to the role
      of shedding membrane-derived vesicles from the B-cell surface.

PMID- 8152298
TI  - Analysis of the p53 gene in myeloid malignancies associated with chromosomal
      abnormalities involving the short arm of chromosome 17.
AB  - p53 protein is encoded by a tumor-suppressor gene located on the short arm of
      chromosome 17. We looked for mutations or rearrangements of the p53 gene in five
      patients with acute transformation of a chronic myeloproliferative disorder and
      cytogenetic anomalies involving the short arm of chromosome 17. Two patients had
      a isochromosome i(17q); three more patients showed the presence of unbalanced
      translocations involving chromosome 17. One of these patients had a single base
      pair deletion, causing a frameshift mutation, in the exon 5 of the p53 gene. The
      karyotype of this patient showed a translocation t(5;17)(q11;p11), with loss of a
      normal homologue of both chromosomes 5 and 17. In all other cases the
      configuration of the p53 gene, as tested by PCR-SSCP analysis of exons 5 to 9 and
      Southern blot, was normal. Our data suggest that mutations of the p53 gene occur
      in a minority of hemopoietic malignancies characterized by monosomy for the short
      arm of chromosome 17. However, the unbalanced translocation t(5q;17p) could be a
      chromosomal abnormality specifically associated with loss of function of the p53
      gene.

PMID- 8152299
TI  - Identification of tumor-associated antigen that is expressed on bovine leukemia
      virus-induced lymphosarcoma cells and expression of its human homologue in human
      T-cell lymphotrophic virus I-infected cell lines.
AB  - By using the monoclonal antibody (MAb) c143 against tumor-associated antigen that
      is expressed in tumor cells of cattle with bovine leukemia virus (BLV)-induced
      enzootic bovine leukosis (EBL), we found a novel bovine MHC class II-related
      antigen which consists of alpha chain (36-37 kDa) and beta chain (32 and 34 kDa).
      The nature of the c143 antigen was different from previously identified class II
      antigens, such as DR and DQ, as indicated by test for reactivities with mouse L
      cell transfectants expressing human class II antigens, sequential
      immunoprecipitation and tryptic peptide mapping. With the progression of EBL, the
      number of cells carrying the c143 antigen increased, and the beta chain was
      specifically phosphorylated at serine residue(s) in lymphosarcoma cells and the
      cell lines derived from them. A marked difference between expression patterns of
      the c143 antigen and the class II antigens was observed in lymph nodes from BLV
      free and -infected animals. Although bovine mixed lymphocyte reaction (MLR) was
      inhibited by the addition of MAbs against class II antigens, the c143 MAb did not
      inhibit a lymphoproliferative response of T cells in the MLR, suggesting that the
      function of this antigen is distinct from those of classical class II molecules.
      Significantly, although the human homologue of the c143 antigen is expressed
      little if at all in human T-cell lines, such as CEM, Molt-4, Jurkat and HPB-ALL,
      its expression become apparent in T-cell lines infected with human T-cell
      lymphotrophic virus I (HTLV-1).

PMID- 8152300
TI  - Molecular mechanisms of tumor progression in chronic myeloproliferative
      disorders.
AB  - We have investigated the involvement of tumor suppressor genes (p53 and RB1) and
      dominantly acting oncogenes (Ras family genes) in BCR/ABL positive and negative
      chronic myeloproliferative disorders (CMPD) at different stages of the disease,
      including 26 cases of BCR/ABL+ chronic myeloid leukemia (CML) blast crisis, 9
      myelosclerosis with myeloid metaplasia, 4 polycythemia vera, 10 essential
      thrombocythemia, 1 juvenile CML, and 8 BCR/ABL- CML. The presence of mutations in
      p53 exons 5 through 9, as well as in RB1 exons 10-27 and in N-, K-, H-Ras exons 1
      and 2 was tested by the PCR-Single Strand Conformation Polymorphism technique and
      by PCR-Direct Sequencing. In addition, Southern blot analysis was used to
      investigate the occurrence of gross rearrangements in the p53 gene as well as
      loss of heterozygosity at 17p13, the site of p53. Acute phase BCR/ABL-CMPD cases
      displayed a high frequency of p53 (2/7) and Ras (3/7) lesions, whereas BCR/ABL-
      CMPD in chronic phase displayed only germline p53 and Ras sequences. Conversely,
      p53 inactivation was restricted to only 1/26 cases of BCR/ABL+ CML blast crisis.
      No alterations in the RB1 gene were detected in any of the cases analyzed. These
      data indicate that p53 inactivation and/or Ras activation might play a role in
      acute transformation of BCR/ABL- CMPD and that the molecular mechanisms of tumor
      progression may be different in BCR/ABL+ versus BCR/ABL-CMPD.

PMID- 8152301
TI  - Activated production of metalloproteinases in Ki-ras-transformed human
      osteosarcoma cells.
AB  - The human osteosarcoma cell culture HOS does not produce matrix
      metalloproteinases (MPs). However, after transformation with the Ki-ras oncogene,
      the resulting culture (KHOS) produced readily detectable MPs. The molecular
      weight of the major MP was 66 kDa, while the molecular weights of two other minor
      bands were 71 kDa and 60 kDa. The activity of all three enzymes was inactivated
      by treatment with ethylene diaminetetra acetic acid, indicating that they are
      probably MPs. The substrate preference of the 66-kDa MP (in decreasing order) was
      gelatin and collagens V, I, III, and IV. Treatment of the MPs with p
      aminophenylmercuric acetate led to the appearance of 62-kDa activated enzyme. The
      MP produced by KHOS cells did not react with the monoclonal anti-rat stromelysin
      antibody MC. Treatment of KHOS cells with retinoic acid and dexamethasone, which
      are known to suppress c-fos/c-jun and AP-1, suppressed the production of the MPs.
      Therefore, the activation of MPs by Ki-ras in KHOS cells may involve c-fos/c-jun
      and the AP-1-responsive pathway.

PMID- 8152302
TI  - Integration of human herpesvirus-6 (HHV-6) genome in chromosome 17 in two
      lymphoma patients.

PMID- 8152303
TI  - Biochemical and genetic studies of Epstein-Barr virus latent membrane protein 2.
AB  - Epstein-Barr Virus (EBV) causes infectious mononucleosis in normal adolescents
      and malignant B lymphocyte proliferation in immune compromised patients, in
      marmosets, or upon transfer of infected human B lymphocytes into SCID mice. EBV
      is also etiologically associated with African Burkitt's lymphoma, Hodgkin's
      Disease, and nasopharyngeal cancer. EBV transformed, latently infected B
      lymphocytes contain EBV episomes and eight virus encoded proteins. Six are
      nuclear proteins (EBNAs) and two are the integral membrane proteins, LMP1 and
      LMP2. These eight proteins are presumed to mediate latent virus infection or B
      lymphocyte proliferation and are thus under intense scrutiny. Besides EBNA1,
      which is required for episome maintenance, LMP1 and LMP2, are the two
      transformation associated proteins that are most consistently detected in EBV
      related malignancies, and the LMP2 message is the only message detected in PCR
      analysis of B lymphocytes from individuals harboring EBV latent infections. LMP2
      associates with src family tyrosine kinases, a 70 kda cell phosphoprotein, LMP1
      and several other unidentified cell proteins. LMP1 is a key mediator of EBV's
      effects on inducing B lymphocyte activation and adhesion molecules and is a
      transforming oncogene in rodent fibroblasts. The association of these two EBV
      encoded membrane proteins could create a macromolecular complex mediating
      constitutive B lymphocyte activation through normal cell signal transduction
      pathways. LMP2 might may control activation of lytic replication or down regulate
      the activation state of EBV infected cells allowing persistence in the human
      host.

PMID- 8152304
TI  - Mechanism of transcriptional activation of viral and cellular genes by oncogenic
      protein of HTLV-1.
AB  - Regulatory protein Tax of human T cell leukemia virus type 1 (HTLV-1) positively
      regulates the transcription of its own genome and specific cellular genes, and
      contributes to the pathogenicity in ATL, HAM/TSP and other associated diseases.
      The one mechanism of the transcriptional activation includes binding of Tax
      protein in nucleus to enhancer binding proteins of CREB, CREM, NF-kappa B p50, NF
      kappa B p105 and SRF which bind to enhancer DNA. The other includes Tax-binding
      to NF-kappa B proteins in the cytoplasm resulting in nuclear translocation of
      active transcription factors. The interaction of Tax with cellular transcription
      factors thus ultimately results in cellular proliferation, immortalization and
      transformation leading to specific diseases.

PMID- 8152305
TI  - Cytotoxic T cell response and expression of the target antigen in HTLV-I
      infection.
AB  - The cytotoxic T cell response of peripheral blood mononuclear cells (PBMC) to in
      vitro stimulation with human T cell leukemia virus type I (HTLV-I) was compared
      among HTLV-I-infected individuals with various clinical conditions. Induction of
      HTLV-I-specific cytotoxic T lymphocytes (CTL) was observed in 57% of asymptomatic
      HTLV-I carriers, 86% of patients with HTLV-I associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) or other HTLV-I-related inflammatory diseases, and
      18% of adult T cell leukemia (ATL) patients. HTLV-I p40tax, one of the major CTL
      target antigens, has an epitope strongly associated with HLA-A2. HTLV-I p40tax
      specific CTL were frequently induced from HLA-A2-positive donors with HTLV-I
      related inflammatory diseases regardless of neurological symptoms, but not from
      all the HLA-A2-positive HTLV-I-infected individuals tested. Leukemic cells of an
      ATL patient with HLA-A2, whose PBMC did not show an HTLV-I-specific CTL response,
      could be lyzed by p40tax-specific CTL derived from an HAM/TSP patient. This
      indicates that i) the presence of a certain HLA presenting CTL epitopes is not
      the sole determinant of the individual CTL response to HTLV-I, ii) HTLV-I
      specific CTL act as potential effectors of anti-tumor surveillance in vivo. The
      role of HTLV-I-specific CTL, however, may be limited by another in vivo mechanism
      suppressing the expression of HTLV-I antigens. This suppression, presumably
      mediated by a plasma factor and commonly observed in HTLV-I-infected individuals,
      could be one reason for the persistence of HTLV-I-infection.

PMID- 8152306
TI  - Recognition by human sera of a variable region of the surface glycoprotein of
      HTLV-I.
AB  - The region comprised between the amino acids 175 and 199 of the HTLV-I envelope
      surface glycoprotein is one of the immunodominant domains of this molecule. In
      this region, which is well recognized by sera from HTLV-I infected patients, a
      substitution of the proline at position 192 by a serine has been described in
      some isolates. Because this mutation could modify the secondary structure of the
      glycoprotein molecule, we studied the inference of the presence of proline or
      serine on the recognition of the region 175-199 by human sera. For this, three
      peptides have been synthetized (a 25-mer 175-199 corresponding to the sequence of
      the ATK prototype, and two internal 10-mer 190-Pro-199 and 190-Ser-199 having a
      proline or a serine at position 192) and tested by immunosorbent assay. While
      most sera reacted with 190-Pro-199 and with 190-Ser-199 synthetic peptides, a
      differential recognition was observed according to the pathology associated to
      HTLV-I infection. Moreover sera corresponding to patients infected with a virus
      harboring a serine at position 192 were found to recognize only the 10-mer with a
      serine. These data indicates that HTLV-I is subject to antigenic variability.

PMID- 8152307
TI  - Intervention of maternal transmission of HTLV-1 in Nagasaki, Japan.
AB  - Seroepidemiological and laboratory virological evidences strongly suggested that
      endemicity of HTLV-1 in Nagasaki Japan depends on maternal infant infections via
      breast milk. The most obvious way to prove this concept was an intervention study
      with refraining from breast-feeding by carrier mothers. Most infected babies
      seroconverted by the age of 12 months, which made it possible to diagnose the
      infection at the age of 12 months for the statistical purpose. Serology and PCR
      on both adults and children were consistent each other, suggesting the absence of
      seronegative carriers. The intervention study revealed that approximately 80% of
      maternal infection was prevented by refraining from breast feeding by carrier
      mothers. The remaining fraction of infections in formula-fed babies suggested an
      alternative infection pathway. Although intrauterine infections has been
      suggested by others to explain the PCR-positive cord blood samples. However,
      groups of cord blood-positive children and seroconverted children were distinct
      each other. Therefore, the presence of HTLV-1 provirus in the cord blood can not
      be a marker of intrauterine infection. Mothers who infected a child has
      approximately 10 times higher risk of another infection for the next baby than
      those who did not.

PMID- 8152308
TI  - Effect of the acute promyelocytic leukemia PML/RAR alpha protein on
      differentiation and survival of myeloid precursors.
AB  - Acute promyelocytic leukaemia is characterized by an expansion of haematopoietic
      precursors arrested at the promyelocytic stage (1). The differentiation block can
      be reversed by retinoic acid, which induces blast differentiation both in vitro
      (2) and in vivo (3-4). Acute promyelocytic leukaemia is also characterized by a
      15;17 chromosome translocation (5) with breakpoints within the retinoic acid
      alpha receptor (RAR alpha) gene on 17 and within the PML gene, that encodes a
      putative transcription factor of unknown function (6-7), on 15 (8-10). As a
      consequence of the translocation a PML/RAR alpha gene is formed. It is
      transcriptionally active and encodes a PML/RAR alpha fusion protein detectable in
      all APL cases (11-14). We expressed the PML/RAR alpha protein in U937 myeloid
      precursor cell line and show that they: 1) lose the capacity to differentiate
      under the action of different stimuli (vitamin D3, transforming growth factor
      beta 1); ii) acquire enhanced sensitivity to retinoic acid; iii) exhibit a higher
      growth rate that is due to a reduction in apoptotic cell death. These results
      provide the first evidence of biological activity of PML/RAR alpha and
      recapitulate critical features of the promyelocytic leukemia phenotype.

PMID- 8152309
TI  - Interactions between HTLV-I Tax and NF-kappa B/Rel proteins in T cells.
AB  - Members of the NF-kappa B/Rel family of transcription factors are involved in the
      transcriptional regulation of numerous polypeptides important to the immune
      response and cellular growth. Several genes regulated in part by NF-kappa B/Rel
      such as interleukin 2, IL-2 receptor alpha, and GM-CSF are trans-activated via an
      indirect association with the HTLV-I Tax protein in virus-infected and
      transformed T cells. In this study, we have investigated the interactions between
      Tax and NF-kappa B/Rel in an attempt to elucidate the mechanism of Tax mediated
      trans-activation and its role in leukemogenesis. Transfection studies were
      performed in Jurkat T cells using expression vectors for individual NF-kappa B
      subunits and the Tax protein as well as an NF-kappa B regulated reporter plasmid.
      NF-kappa B proteins differentially trans-activated the HIV-1 enhancer-CAT
      reporter; co-expression of Tax abrogated the inhibitory effect of I kappa B alpha
      and a trans-dominant negative mutant of p65 (p65 delta), indicating that Tax was
      a trans-dominant activator of NF-kappa B-regulated genes. Co-immunoprecipitation
      studies with extracts from transfected cells and NF-kappa B and Tax subunit
      specific antibodies revealed that Tax did not co-immunoprecipitate with p50/p105,
      c-Rel, or I kappa B; however, antibody specific to p65 was able to co
      immunoprecipitate a 40kDa protein from Tax-transfected cells. Previous studies
      have demonstrated a physical interaction between Tax protein and p100, indicating
      that Tax may preferentially associate with specific NF-kappa B proteins.

PMID- 8152310
TI  - Some epidemiological features of the human T-cell lymphotropic virus type I (HTLV
      I) and ATL in Nigerians.
AB  - With a seroprevalence rate (SPR) of 6%-10% among healthy adult blood donors
      (ABD), Nigeria and other African locales represent an endemic zone for HTLV-I. We
      studied SPR in patients with leukaemia, lymphomas, solid tumours, and chronic
      disorders, as well as in groups of men and women with varying sexual lifestyles.
      Serum specimens were screened with ELISA and then confirmed with Western blot
      (WB). Sexual practices were investigated among volunteers of different sexual
      backgrounds by means of a questionnaire. Female prostitutes (FP) (13.0%) and
      patients with sexually transmitted diseases (STDP) (16.7%) had the highest SPR
      while a low rate occurred in religious celibate males (RCM) but not in religious
      celibate females (RCF) (11.8%). Heterosexual activity as well as geographical
      location of the place of birth constituted the most important risk factors for
      HTLV-I. HIV antibodies were demonstrable in none of the study subjects. ATL was
      associated with 100% SPR (4/4) while SPR in other clinical states were not
      different from normal. Western blot profile was rarely of strong poly band but
      more frequently of weak oligo band pattern with absent or weak p19 compared to
      p24. Only 18% of non Hodgkin's lymphoma in Ibadan, Nigeria was seropositive
      compared to 50% and > 60% in Japanese and Caribbean endemic zones respectively.
      The high SPR and aberrant WB profiles indicate reactivity to HTLV-I and to an
      HTLV-II-like activity, probably a new virus in the region. Excluding the aberrant
      WB profile, SPR based on HTLV-I-related profile was 3.8%-4.8% in ABD, 13% in FP,
      10% in STDP, 1.9% in RCM, 0% in RCF, and 25% in ATL patients. The HTLV-II-related
      profile showed no such heterosexual association, but occurred in 75% of ATL
      patients. HTLV-I and probably and an HTLV-II-like virus appear to play a role in
      STD and lymphoma epidemiology in Nigeria.

PMID- 8152311
TI  - Identification of HTLV-I 21 bp repeat-specific DNA-protein complexes.
AB  - The human T cell lymphotropic virus type 1 (HTLV-I)-encoded protein, Tax, is
      capable of transcriptionally trans-activating HTLV-I by interacting with specific
      sequences in the HTLV-I long terminal repeat (LTR) which comprise an inducible
      enhancer containing three imperfect tandem repeats of a 21 bp sequence. Evidence
      suggests that Tax is incapable of directly interacting with DNA; therefore, Tax
      most likely regulates transcription via interaction with cellular factors. In
      addition to a role in Tax-mediated trans-activation, cellular factors are also
      critical elements in basal HTLV-I LTR-directed transcription. Therefore,
      characterization of cellular factors which interact with the 21 bp repeat
      elements is essential to understanding the molecular mechanisms involved in both
      basal and Tax-mediated transcription from the HTLV-I LTR. Utilizing
      electrophoretic mobility shift (EMS) analyses, we have detected 21 bp repeat
      specific DNA-protein complexes when nuclear extracts derived from cells of
      lymphoid (Jurkat, SupT1, and H9) and monocytoid (U937) origin were reacted with
      each of the three 21 bp repeat elements. Furthermore, results from EMS
      competition analyses utilizing unlabeled 21 bp repeats as competitor DNAs have
      indicated a difference in the ability of each unlabeled 21 bp repeat to compete
      for the specific DNA-protein complexes formed between the nuclear extracts and
      radiolabeled 21 bp repeats. In each case, the most effective competitor was the
      homologous, unlabeled 21 bp repeat element. These results demonstrate that there
      are 21 bp repeat-specific DNA-protein complexes and suggest functional
      differences among the three 21 bp repeat elements.

PMID- 8152312
TI  - Human T-lymphotropic virus type I uveitis.
AB  - In addition to adult T-cell leukemia (ATL) and chronic myelopathy (HAM/TSP), our
      current study indicates that human T lymphotropic virus type I (HTLV-I) is a
      causative agent for a specific type of uveitis with unknown etiology (idiopathic
      uveitis). The present paper describes the seroepidemiological, clinical, and
      molecular biological evidences that indicate uveitis seen in HTLV-I asymptomatic
      carriers (HTLV-I uveitis) is a distinct clinical entity. In an HTLV-I endemic
      area in Japan, the seroprevalence of HTLV-I in idiopathic uveitis was 38%, while
      those in uveitis with defined etiology and in non-uveitic ocular diseases were
      10% and 19%, respectively. Strikingly, the HTLV-I seroprevalence in younger aged
      patients (20-49 years) with idiopathic uveitis was 49%, while only 8% in the
      control group (P < 0.001). A very similar observation was recorded even in HTLV-I
      less endemic area, suggesting that HTLV-I infection plays a role as a risk factor
      for idiopathic uveitis. Clinical analysis revealed that an intermediate uveitis
      characterized by moderate opacities in the vitreous body and retinal vasculitis
      was seen in the majority the patients. The proviral DNA of HTLV-I was detected
      from inflammatory cells in the eye of all tested patients using PCR technique.
      These data thus indicate that HTLV-I is closely related to a certain type of
      uveitis and the uveitis (HTLV-I uveitis) is a distinct clinical entity.

PMID- 8152313
TI  - Antiapoptotic effect of c-fes protooncogene during granulocytic differentiation.
AB  - The c-fes protooncogene is expressed at high levels in the terminal stages of
      granulocytic differentiation. Its product, p92c-fes, exhibits a tyrosine-kinase
      activity and is involved in the cellular response to GM-CSF, but its role is not
      yet clarified. To study this problem, the c-fes protooncogene expression has been
      inhibited in HL60 cells and in fresh leukemic blast cells of Acute Promyelocytic
      Leukemia (APL) induced to differentiate with All-Trans-Retinoic Acid (ATRA).
      Inhibition of c-fes function was obtained by treatment of the cells with a
      specific antisense oligomer complementary to the 5' region of the c-fes mRNA. It
      was observed that the cells, rather then differentiate to granulocytes, underwent
      premature cell death showing the morphological and molecular characteristics of
      apoptosis. Superimposable results are obtained on blast cells from APL. It is
      possible to conclude that the loss of cell viability that occurs during the in
      vitro differentiation of myeloid cells, after the complete inhibition of c-fes
      expression and treatment with ATRA, is due to activation of programmed cell death
      rather than an accelerated differentiation. Our data suggest that the c-fes
      product is essential for the survival of myeloid cells during differentiation.

PMID- 8152314
TI  - Comparative analysis of the T cell receptor V beta repertoire in various lymphoid
      tissues from HIV-infected patients: evidence for an HIV-associated superantigen.
AB  - The search to identify HIV-associated molecules with superantigenic properties
      has focussed on demonstration of T cell receptor V beta subset-specific
      perturbations in HIV-infected patients. In this report, the V beta repertoire of
      two HIV patients was studied in lymph nodes, where HIV-1 replication is the most
      intense, and compared to the repertoire found in peripheral blood. Use of this
      fully MHC-compatible system has allowed identification of a small, partly
      overlapping set of V beta determinants which appear significantly perturbed in
      HIV-1 infection. These results are consistent with the presence of an HIV
      associated superantigen.

PMID- 8152315
TI  - Apoptosis by genetic engineering.
AB  - Apoptotic cell death is physiological. Malignant cells often escape programmed
      cell death. Many genes that promote (p53) or antagonize (bcl-2, fes) apoptosis
      have been recognized. Apoptosis promoter genes can be activated by growth factor
      or hormone withdrawal in growth factor- or hormone-dependent tumor cells.
      Malignant cells acquiring apoptosis-resistance, still can be killed by cytotoxic
      lymphocytes releasing lymphotoxins. This phenomenon gives further support to the
      therapeutic use of activated and expanded lymphocyte populations and/or apoptosis
      inducing cytokines. Chemotherapeutic agents (esp. topoisomerase inhibitors)
      frequently kill tumor cells by activating programmed cell death (PCD).
      Biologicals and chemotherapeutics may synergize in evoking apoptosis. We propose
      the cloning of apoptotic genes and their transfer by transfection in vivo into
      tumor cells. While transfection of genes into tumor cells in vitro is widely
      practiced, the lack of proper technology for transfection in vivo and the unknown
      aspects of apoptotic cell death are recognized.

PMID- 8152317
TI  - Sexually dimorphic effects of aging on tuberoinfundibular dopaminergic neurons
      and lactotropes of rats.
AB  - The effect of aging on plasma prolactin (PRL) levels, hypothalamic
      tuberonifundibular dopaminergic (TIDA) neurons and pituitary lactotropes was
      evaluated in prolactinoma-free young (5-month-old) and old (23- to 24-month-old)
      Long-Evans rats of either sex. The young female rats were in diestrus, the old
      ones in recurrent pseudo-pregnancy. The tyrosine hydroxylase (TH)-labelled
      neurons in the arcuate nucleus (AN) and axons in the median eminence (ME) as well
      as the PRL-labelled lactotropes in the pituitary gland were studied by
      morphometry and densitometric immunohistochemistry. Further, we investigated the
      secretory function of isolated lactotropes by reverse hemolytic plaque assay
      (RHPA) and by cell culture in comparable animal groups. Compared with young
      animals, the plasma PRL levels of old rats of both sexes were similar or reduced.
      All morphometric and densitometric measurements of the AN neurons, ME axons
      (except number) and pituitary lactotropes were comparable in young and old female
      rats. In old male rats the AN and ME measurements were mostly decreased, while
      the lactotropes remained almost unchanged. The RHPA generally showed a reduced
      PRL release from lactotropes of old animals of both sexes. The PRL release from
      the cultured lactotropes, on the contrary, was greatly increased in old female
      rats and unchanged in old male rats. Our functional and morphological data
      suggest that the in vivo function of lactotropes in old prolactinoma-free female
      and male rats does not seem to be strongly influenced by the mildly reduced TIDA
      neuron activity, yet emphasize the differences of the aging process in the two
      sexes.

PMID- 8152316
TI  - The development of age-related deficits in several presynaptic processes
      associated with brain [3H]acetylcholine release.
AB  - Isolated nerve terminals were prepared from the neocortices and striate cortices
      of Fischer 344 rats from 6 to 26 months of age and then assayed for release of
      newly synthesized [3H]acetylcholine (ACh) triggered by secretagogues with
      different mechanisms of action: 35 mM K+, 10 microM veratridine and 5 microM
      A23187. Secretagogue-induced release of newly synthesized [3H]ACh decreased with
      age in both brain regions, with reductions in A23187-induced release paralleling
      those seen with depolarizing agents. This observation was consistent with the
      hypothesis that aging attenuates the release-triggering ability of calcium ions
      coincident with or before it affects voltage-sensitive calcium influx. In
      neocortex, phorbol-stimulated translocation of protein kinase C (PKC) activity
      was attenuated in isolated nerve terminals concomitantly with A23187-induced
      release deficits. These results suggest that one of the earliest deficits in the
      ACh-release process may involve intracellular calcium potency, which may be
      associated with the onset of functional PKC deficits. Both brain regions also
      displayed gradual, age-related reductions in [3H]ACh synthesis, but this effect
      was more pronounced in the striatum. Choline acetyltransferase (CAT) activity
      decreased only in the striatum with aging.

PMID- 8152318
TI  - Alterations of anorectic cytokine levels from plasma and cerebrospinal fluid in
      idiopathic senile anorexia.
AB  - Plasma and cerebrospinal fluid (CSF) concentrations of two well-known satiety
      cytokine peptides have been measured in elderly persons with idiopathic anorexia
      and normal weight healthy subjects in a similar age range. Plasma and CSF levels
      of tumor necrosis factor alfa (TNF alpha) and interleukin-1 beta (IL-1 beta) were
      assayed by commercially available kits. Elderly under-weight anorectic patients
      had significantly lower levels of TNF alpha but unchanged concentrations of IL-1
      beta in both plasma and CSF when compared to controls. In addition to
      significantly lower levels of TNF alpha in CSF, we found a positive correlation
      between the body mass index and CSF TNF alpha concentrations (r = 0.61, P < 0.05)
      in the anorectic group. CSF IL-1 beta concentrations showed a significant
      negative correlation with plasma albumin levels in senile anorectics (r = -0.66,
      P < 0.05) but not in controls. On the basis of our findings, we conclude that a
      decrease in plasma and CSF TNF alpha concentrations could have beneficial effects
      for the primary anorexia of aging both at central level to offset anorexia and at
      peripheral sites decreasing tissue catabolism.

PMID- 8152319
TI  - Effect of age and extent of dietary restriction on hepatic microsomal lipid
      peroxidation potential in mice.
AB  - Lipid peroxidation potential in hepatic microsomes from young and old mice
      following two different caloric restriction regimens was measured by a
      colorimetric thiobarbituric acid method under conditions where Fe2+ autoxidation
      and free oxygen radical production were undetectable. Peroxidation was highest in
      the young (3.5-month-old) slightly restricted group (caloric intake 75% of ad
      libitum mice) but very low in young severely restricted (caloric intake 50% of ad
      libitum mice) and in both old (27-month-old) slightly and severely restricted
      groups. Very old (45-month-old) severely restricted animals had intermediate
      lipid peroxidation potentials. Fatty acid composition of liver homogenates was
      also determined. Significant differences between groups were found for only three
      fatty acids. Linoleic acid (18:2(n-6)) decreased in aged slightly restricted
      animals while it remained stable in severely restricted animals during aging.
      Dihomo-gamma-linolenic acid (20:3(n-6)) was higher in very old restricted animals
      than in old slightly restricted animals. Docosahexaenoic acid (22:6(n-3))
      decreased in old slightly restricted animals. These results indicated that the
      effect of diets on hepatic fatty acid composition and the potential for
      microsomal lipid peroxidation in mice was dependent on the degree of caloric
      restriction and age.

PMID- 8152320
TI  - The female longevity phenomenon. Hypotheses on some molecular and cell biology
      aspects.
AB  - The most relevant theories on the sex-dependent longevity at population level are
      critically re-examined in the light of the knowledge available today on the aging
      process at cellular and molecular level. The aim of this perspective is to help
      in the understanding of the cellular and molecular bases of longevity and to
      indicate the most suitable biological models of investigation.

PMID- 8152321
TI  - Erythrocyte behavior in free-flow electrophoresis is independent of erythrocyte
      age.
AB  - Enzyme activities (acetylcholinesterase, fluorescein diacetate hydrolase,
      superoxide dismutase), membrane protein band 4.1a/4.1b ratio and density of
      various fractions of rabbit erythrocytes separated did not show differences
      between various fractions of erythrocytes separated by free-flow electrophoresis.
      Also, electric field deflection of lightest and densest fractions of erythrocytes
      did not differ. These results point to the lack of changes in surface charge
      density during in vivo erythrocyte aging.

PMID- 8152322
TI  - Phencyclidine reduces inherited neocortical spindling in DBA/2J mice.
AB  - The role of phencyclidine (PCP) in the control of the spike-and-wave spindling
      episodes (S&W) which can be spontaneously recorded in the electrocorticogram
      (ECoG) of DBA/2J mice was investigated. PCP (0.1-0.5-1.0-5.0 mg/kg/i.p.) dose
      dependently reduced both S&W number and duration of DBA/2J mice. PCP reduction is
      significant 30-60 min after drug administration and lasts for the whole duration
      of the recording period (240 min). These results suggest that PCP may play an
      important regulatory role on brain excitability.

PMID- 8152323
TI  - Differing effects of vasopressin on regional cerebral blood flow of dogs
      following intracisternal vs. intra-arterial administration.
AB  - We investigated the differential effect of the intracisternal and intraarterial
      administration of vasopressin on the regional cerebral blood flow (rCBF) in the
      parietal cortex of dogs. Regional CBF, velocity and blood volume were assayed by
      laser flowmetry. The intracisternal injection of 1 nmol vasopressin significantly
      increased the rCBF and velocity, without affecting blood volume. However, the
      intravertebral arterial injection of 1 nmol vasopressin significantly decreased
      the rCBF and velocity. This discrepancy can be explained by a difference in the
      affected vasculature; large blood vessels in the subarachnoid space vs. whole
      cerebral vascular system. The intracisternal and intraarterial injection of the
      nitric oxide inhibitor NG-monomethyl-L-arginine reduced the rCBF from the base
      line, and significantly suppressed the rCBF elevation induced by vasopressin. The
      effect of vasopressin may be considered as the summation of the increased flow
      from the dilated large vessels via the release of nitric oxide from the
      endothelium, and of the decreased flow from the contracted small vessels.

PMID- 8152324
TI  - Vasoactive intestinal peptide encapsulated in liposomes: effects on systemic
      arterial blood pressure.
AB  - The purpose of this study was to determine whether encapsulation of vasoactive
      intestinal peptide (VIP) in liposomes enhances its vasoactive effects. Liposomes
      were formed from a solution of VIP in phospholipids and cholesterol, resulting in
      incorporation of 0.008 mole peptide/mole phospholipid. Leakage of VIP from the
      liposomes was undetectable over several days of incubation at 4 degrees C in 0.15
      M sodium chloride. Under conditions permitting rapid hydrolysis of VIP by
      trypsin, there was no breakdown of the encapsulated peptide. Increasing
      concentrations of the liposome-encapsulated VIP administered intravenously to
      anesthetized hamsters produced a concentration-dependent decrease in the mean
      arterial blood pressure. The duration and magnitude of the hypotensive effect of
      the encapsulated VIP was significantly greater (p < 0.05) compared to equivalent
      concentrations of the unencapsulated peptide. Infusion of empty liposomes was
      without significant effect on the mean arterial blood pressure. We conclude that
      encapsulation of VIP in liposomes potentiates the blood pressure-lowering effect
      of the peptide.

PMID- 8152325
TI  - Regulation of glycogen synthase activity in isolated rat adipocytes by
      levamisole.
AB  - The effect of levamisole on glycogen synthase activity in isolated adipocytes was
      studied. The addition of levamisole to these cells resulted in an acute
      concentration-dependent increase in glycogen synthase activity. In contrast,
      epinephrine, dibutyryl cyclic AMP (DcAMP) and cysteamine decreased glycogen
      synthase activity. The stimulatory effect of levamisole on the activity of the
      enzyme was not affected by the presence of epinephrine but was diminished when
      either DcAMP or cysteamine was present. The results of this study suggest that
      levamisole increases adipocyte glycogen synthase activity by a mechanism that can
      be reversed by the elevation of cAMP.

PMID- 8152326
TI  - Sexually low performing male rats die earlier than their high performing peers
      and (-)deprenyl treatment eliminates this difference.
AB  - Out of 1600 sexually inexperienced 28-week old Wistar-Logan male rats 94 sexually
      inactive ('low performing', LP) and 99 highly active ('high performing', HP) rats
      were selected. The rats were treated from the 8th month of their life three times
      a week, subcutaneously, with either 0.9% NaCl or 0.25 mg/kg (-)deprenyl until
      they died. Their copulatory activity was tested once a week and their learning
      performance was measured in the shuttle box once in three months. The salt
      treated LP rats (n = 44) never displayed ejaculation during their life time, they
      were extremely dull in the shuttle box and lived 134.58 +/- 2.29 weeks. Their (
      )deprenyl-treated peers (n = 48) became sexually active, their mating performance
      was substantially increased and lived 152.54 +/- 1.36 weeks, significantly longer
      than their salt-treated peers and as long as the salt-treated HP rats. The salt
      treated HP rats (n = 49) displayed 14.04 +/- 0.56 ejaculations during the first
      36-week testing period and due to aging they produced 2.47 +/- 0.23 ejaculations
      between the 73-108th week of testing. Their learning performance was high. They
      displayed 78.45 +/- 3.01 conditioned avoidance responses (CAR) during the first
      36-week testing period and this dropped to 50.67 +/- 2.99 (p < 0.01) during the
      73-108th week of testing. They lived 151.24 +/- 1.36 weeks, significantly (p <
      0.001) longer than their LP peers. The (-)depre-nyl-treated HP rats (n = 50) were
      sexually much more active than their salt-treated peers. They displayed 30.04 +/-
      0.85 ejaculations during the first 36-week testing period and 7.40 +/- 0.32
      ejaculations between the 73-108th week of testing. Also their learning
      performance was substantially increased. They produced 113.98 +/- 3.23 CARs
      during the first 36-week-testing period and 81.68 +/- 2.14 CARs during the 73
      108th week of testing. They lived 185.30 +/- 1.96 weeks, significantly more than
      their salt-treated peers and out of the 50 rats 17 lived longer than the
      estimated technical life span (TLS).

PMID- 8152328
TI  - Urinary excretion of amphetamine and 4'-hydroxyamphetamine by Sprague Dawley and
      dark Agouti rats.
AB  - Urinary excretion of amphetamine and 4'-hydroxyamphetamine has been studied in
      male and female Sprague Dawley (SD) and Dark Agouti (DA) rats. The DA rat is an
      animal model for the cytochrome P450 (P450) 2D poor metabolizer. Rats were given
      d-amphetamine sulfate (5 mg/kg, i. p.) and urines were collected at 12 hour
      intervals for extraction and analysis of the amphetamines by HPLC. There was no
      significant difference between the sexes of either SD and DA rats in urinary 4'
      hydroxyamphetamine and amphetamine excretion, but significant differences were
      seen between the two strains. The percentage of dose per ml urine recovered as 4'
      hydroxyamphetamine from the urine over 24 hours was 11.1 and 9.1 in the SD male
      and female rats, and 2.3 and 2.5 in DA male and female rats, respectively. The
      percentage of dose per ml urine recovered as amphetamine was correspondingly
      lower in the SD male and female rats, 1.1 and 1.0, than that of the DA male and
      female rats, 5.9 and 5.0. These results support our hypothesis that P450 2D is
      involved in hepatic 4'-hydroxylation of amphetamine in rats.

PMID- 8152327
TI  - Tissue distribution of histamine N-methyltransferase-like immunoreactivity in
      rodents.
AB  - The rat kidney histamine N-methyltransferase was purified to homogeneity from
      Escherichia coli transfected with its recombinant cDNA. An antiserum to the
      enzyme was raised in rabbit by immunization with the purified protein. Western
      blot analysis of rat tissues with the antiserum revealed a band with identical
      mobility to that of purified enzyme in the extracts of kidney, jejunum, and
      brain, where the enzyme activity was detected. The antiserum cross-reacted with a
      32K protein in mouse liver, brain, stomach, kidney and lung, and a 33K protein in
      guinea pig brain, stomach jejunum, spleen, lung, and kidney. The intensity of the
      staining in western blotting correlated well with the enzyme activity in all the
      tissues in these three species, suggesting that our antiserum is useful for
      quantifying histamine N-methyltransferase protein in rodent tissues.

PMID- 8152329
TI  - In vitro effect of nifedipine on KCl and 5-hydroxytryptamine-induced contractions
      of the sheep coronary, cerebral and pulmonary arteries.
AB  - The aim of the present study was to compare the sensitivity to nifedipine of
      contraction, obtained with 5-hydroxytryptamine (5-HT) and high K+, of arteries
      from three vascular territories (coronary, cerebral and pulmonary), selecting
      arteries of equivalent diameter (0.4-0.8 mm). In the coronary and middle cerebral
      arteries, contraction produced by KCl was abolished by nifedipine 10(-7) M.
      However, in the pulmonary artery 39 +/- 2% (n = 5) of the KCl contraction
      remained in the presence of nifedipine 10(-6) M and a similar sized contraction
      remained in the presence of Ni2+ 10 mM, La3+ 1 mM or Ca(2+)-free conditions.
      Nifedipine caused less inhibition of 5-HT than of KCl in all three arteries. In
      the coronary and middle cerebral arteries 5-HT was inhibited to 55 +/- 9% and to
      55 +/- 4% and in the pulmonary artery to 78 +/- 3% (n = 6) by nifedipine 10(-6)
      M. In conclusion, a comparison of coronary, cerebral and pulmonary arteries, of
      comparable size and from the same species, has shown that there is diversity in
      the sensitivity of 5-HT-induced contraction to inhibition by nifedipine.
      Moreover, the KCl-induced contraction in the sheep pulmonary artery is mediated,
      in part, by a mechanism independent of Ca2+ influx.

PMID- 8152330
TI  - Ontogeny of ovine fetal renal atrial natriuretic factor receptors.
AB  - Ovine fetal renal responses to ANF decrease during the last third of gestation,
      although circulating fetal plasma atrial natriuretic factor (ANF) levels are
      higher than in the maternal circulation, and do not change with gestation. This
      study examined whether previously reported maturational changes in fetal renal
      responses to ANF are due to changes in renal ANF receptor numbers and/or affinity
      during gestation. ANF receptor numbers (Bmax) and dissociation constants (Kd)
      were measured in isolated renal glomeruli from early (95 and 110 day; mean 103 +/
      2) and late gestation (131 and 145 day; mean 138 +/- 2) fetal and maternal
      sheep. Fetal renal ANF receptor Bmax values significantly increased between 103
      and 138 days gestation (13 +/- 3 to 29 +/- 4 fmol/mg protein) but were
      significantly lower than maternal values (60 +/- 13 fmol/mg protein). Fetal ANF
      receptor Kd values also increased significantly (245 +/- 34 to 370 +/- 36 pM),
      with early gestation values significantly lower than maternal values (470 +/- 69
      pM). Thus, the blunted fetal renal response to ANF in late as compared to early
      gestation is not due to reduced ANF receptor numbers. Rather, an increased
      proportion of ANF clearance receptors, reduced post-receptor function and/or
      altered intrarenal hemodynamics may contribute.

PMID- 8152331
TI  - Solubilization and characterization of d-fenfluramine binding sites from bovine
      cerebral cortex.
AB  - Stable d-Fenfluramine binding activity was obtained in high yields, in cholate
      extracts of bovine cerebral cortex crude membrane preparations. Dissociation
      constant (Kd 17 nM), stereoselectivity and the rank order of potencies of various
      serotonin uptake inhibitors were similar to those measured in native membranes.
      The inhibitory effect of Na+ ions was also maintained in the soluble state, since
      the presence of 100 mM Na+ leads to an even greater reduction of the binding than
      in membrane-associated binding sites. Photoaffinity labeling of soluble binding
      sites with p-[125I]d-Fenfluramine has led to the identification of a single
      specific band of molecular weight around 40-50 kDa. This suggests that d
      Fenfluramine binding sites are separate molecular entities from the serotonin
      transporter, that belongs to a family of integral membrane proteins of 68-73 kDa
      molecular weight.

PMID- 8152332
TI  - Anticardiolipin antisera from lupus patients with seizures reduce a GABA receptor
      mediated chloride current in snail neurons.
AB  - The effects of circulating anticardiolipin (ACL) antisera in lupus patients on
      the LP5 central neuron of snail were studied. Both GABA and glutamate increased a
      chloride conductance of the LP5 neuron. The ACL antisera decreased the GABA
      elicited responses in a concentration dependent manner while it had no effect on
      glutamate-elicited responses. The ACL antisera affected neither the resting
      membrane current, nor the membrane conductivity of neuron. Antisera without the
      activity of anticardiolipin did not decrease the GABA-elicited responses. The
      seizure incidence of the patients with higher ACL antisera levels is also higher.
      It is concluded that ACL antisera inhibited the GABA ionophore receptor complex
      in a snail central neuron.

PMID- 8152333
TI  - Direct evidence for erythropoietin-induced release of endothelin from peripheral
      vascular tissue.
AB  - The effect of recombinant human erythropoietin (r-HuEPO, 0.1 to 2.0 U/ml) on
      endothelin-1 (ET-1) release was examined in isolated hind legs perfused with
      Krebs-Ringer solution from normal rats. r-HuEPO increased immunoreactive (ir-) ET
      1 release in a dose-dependent fashion; the maximal percent increment in ir-ET-1
      release evoked by r-HuEPO (2.0 U/ml) was about +210% over the basal rate of
      release. However, r-HuEPO showed no effect on release of angiotensin II,
      thromboxane B2 or vasodilatory prostaglandin I2 from the vasculature. These
      results not only provide direct evidence that r-HuEPO has the potential to
      specifically stimulate release of ET-1 from peripheral vascular beds, but, hence,
      suggest a contributory role of ET-1 in r-HuEPO-induced hypertension in anemic
      human subjects undergoing r-HuEPO therapy.

PMID- 8152334
TI  - Clozapine, a dopamine DA4 receptor antagonist, reduces gastric acid secretion and
      stress-induced gastric mucosal injury.
AB  - Dopamine and its agonists modulate a variety of gastrointestinal functions. In
      light of the increasing attention directed toward novel dopamine receptors and
      compounds that are active at these sites, we examined the effects of a dopamine
      D4 antagonist and putative antipsychotic, clozapine, in a model of conscious
      basal gastric acid secretion and in a model of stress-induced gastric mucosal
      injury. At a dose of 10.0 mg/kg i.p., clozapine significantly inhibited basal
      gastric acid secretion by 84% relative to vehicle. Lower doses (2.5 and 5.0
      mg/kg) were inactive. Doses of 2.5, 5.0 and 7.5 mg/kg i.p. all significantly
      reduced restraint stress-induced gastric mucosal injury in rats. The highest dose
      inhibited gastric lesions by 70% relative to vehicle. We conclude that dopamine
      D4 receptors, present in high concentrations in mesolimbic brain regions,
      modulate gastric function and pathology in addition to mesolimbic D1 receptors,
      whose role in gastrointestinal function is already established.

PMID- 8152335
TI  - An adrenomedullin (ADM) fragment retains the systemic vasodilator activity of
      human ADM.
AB  - The present study was undertaken to investigate the effects of human ADM, a newly
      discovered peptide present in normal human plasma, as well as a fragment of human
      ADM, human ADM13-52, on systemic hemodynamics in the anesthetized cat.
      Intravenous (i.v.) bolus injections of human ADM and human ADM13-52 decreased
      systemic arterial pressure (SAP) in a dose-dependent manner. Since neither
      peptide altered cardiac output, the decreases in SAP reflect reductions in
      systemic vascular resistance. The systemic vasodilator responses to the same
      doses of human ADM and human ADM13-52 in the cat were similar. The present study
      demonstrates the systemic vasodilator activity of ADM is conserved across
      species. The present data suggest that human ADM13-52 or a peptide structurally
      similar to it may mediate the hemodynamic properties of ADM in vivo in man. Since
      cardiac output and heart rate were not altered during the marked systemic
      vasodepressor response to ADM, activation of the ADM vasodilator mechanism may
      represent a therapeutic alternative in the clinical management of hypertensive
      diseases.

PMID- 8152336
TI  - Kainic acid and 4-aminopyridine seizure models in mice: evaluation of efficacy of
      anti-epileptic agents and calcium antagonists.
AB  - Seizures may be induced in mice in response to stimulation of subtypes of
      glutamate receptors by kainic acid or inhibition of certain voltage-dependent
      potassium channels by 4-aminopyridine (4-AP). The anti-seizure efficacy of
      intraperitoneally administered anticonvulsants and Ca++ antagonists to CF-1 mice
      was tested using these models. The order of potency for prevention of kainate
      convulsions and the subsequent lethality was: dihydropyridine Ca++ antagonists
      (nicardipine, nisoldipine > nitrendipine > nifedipine > nimodipine) followed by
      verapamil > prenylamine > diltiazem > flunarizine > remacemide HCl > ethosuximide
      > valproate. In the 4-AP model the order of potency to prevent hind limb tonic
      extension was: MK801(+/-) > lamotrigine > phenytoin, phenobarbital >
      carbamazepine > FPL 12495AA (the desglycine metabolite of remacemide HCl),
      remacemide HCl > flunarizine > prenylamine >>> valproate. Therefore, compounds
      that limit activation of kainate receptors and voltage-operated linked calcium
      channels are active in the kainate model. Agents effective against maximal
      electroshock appear to be effective in the 4-AP model.

PMID- 8152337
TI  - Biochemical and molecular properties of lithium-sensitive myo-inositol
      monophosphatase.
AB  - Myo-inositol monophosphatase is a pivotal enzyme of the inositol second messenger
      system which is specifically inhibited by therapeutic levels of lithium salts,
      implicating inhibition of this enzyme as a potential site of its action in
      bipolar disease. This enzyme has a native molecular weight of 59,000, and has
      traditionally been found in the cytosolic fraction, although a membrane-bound
      form has also been identified. Possessing two identical subunits, this enzyme
      hydrolyzes those monophosphates which are equatorially located within the
      inositol ring, and several nucleoside monophosphates phosphorylated at the 2
      position. Each subunit of the native enzyme contains an active site with
      unusually large caverns as revealed by crystallographic studies, which may
      explain the accommodation of these structurally unrelated substrates. We have
      suggested that the uncompetitive inhibition of this phosphatase by lithium ions
      may prevent the formation of an enzyme-bound non-isomeric (meso) intermediate,
      Mg(2+)-inositol 1,3 or 4,6 cyclic monophosphate when this enzyme hydrolyzes its
      respective isomeric substrates.

PMID- 8152338
TI  - The production of nitric oxide in endothelial cells by amphiphiles.
AB  - Lysophosphatidylcholine, an endogenous detergent is an endothelium-dependent
      smooth muscle relaxant, which acts through the release of nitric oxide. It is
      known to activate a number of membrane-bound enzymes. Because of the relationship
      between detergent action, relaxation of endothelium-intact rabbit aortic strips
      and the release of nitric oxide, we considered the possibility that other
      amphiphiles also produce nitric oxide from endothelial cells. We therefore
      investigated the effect of digitonin on relaxation of precontracted rabbit aortic
      strips and the release of nitric oxide from freshly harvested bovine endothelial
      cells as determined by chemiluminescence. We found that both digitonin and LPC
      release nitric oxide and that this process is inhibited by the NO synthase
      inhibitor N omega-Nitro-L-Arginine Methyl Ester (L-NNAME).

PMID- 8152339
TI  - Role of platelet GpIIb/IIIa receptors in the modulation of platelet plasminogen
      activator inhibitors type-1 (PAI-1) release.
AB  - This study was undertaken to determine the role of platelet glycoprotein (GP)
      IIb/IIIa receptors in the modulation of plasminogen activator type-1 (PAI-1)
      release from human platelets as compared to other platelet functions. To address
      this issue, the effect of various agonists on human platelet aggregation,
      [125I]fibrinogen binding and the release of PAI-1 was examined in normal and
      Glanzmann's thrombasthenic (GT) platelets. In control subjects, maximum platelet
      aggregation and PAI-1 secretion were observed within 5 min in response to the
      different agonists including thrombin, collagen, adenosine diphosphate (ADP), and
      arachidonic acid. Agonist-induced platelet GpIIb/IIIa receptor activation was
      confirmed by [125I]fibrinogen binding analysis. In contrast, platelets from GT
      subjects demonstrated a lack of fibrinogen binding and a lack of an aggregatory
      response to all agonists tested except to the GPIb- mediated aggregation induced
      by ristocetin. However, GT platelets demonstrated normal responsiveness in
      secreting PAI-1 in response to the various agonists. Similarly, when platelet
      GpIIb/IIIa receptors were blocked in normal platelets by the tripeptide Arg-Gly
      Asp (RGD) or the tetrapeptide Arg-Gly-Asp-Ser (RGDS) at 10(-3) M, agonist-induced
      platelet aggregation and fibrinogen binding were blocked, but platelet PAI-1
      release was not blocked. Furthermore, flow cytometric analysis using dual
      fluorescence markers for the platelet GPIIb/IIIa membrane receptors (FITC-labeled
      cyclic RGD analog, XL086) and for the alpha granule (PE-monoclonal antibody for P
      selectin) demonstrated a dissociation between the platelet GPIIb/IIIa receptors
      and granular secretion. These results suggest a lack of a role for platelet
      GpIIb/IIIa receptors in the modulation of platelet PAI-1 release.

PMID- 8152340
TI  - Changes in the activities of protein kinases A, C, and M in dog heart and liver
      following endotoxin administration.
AB  - Changes in the activities of protein kinase A (cAMP-dependent), protein kinase C
      (Ca2+/phospholipid-dependent), and protein kinase M (Ca2+/calmodulin-dependent)
      in dog heart and liver were studied 4 hr following endotoxin injection. Protein
      kinases A and C were extracted and partially purified by DEAE-cellulose
      chromatography. Protein kinase M was extracted and partially purified by DEAE
      cellulose, DEAE-Sephacel, and calmodulin-Sepharose chromatography. The results
      indicate that in the heart, both type I (eluted at low ionic strength) and type
      II (eluted at high ionic strength) protein kinase A activities were unchanged
      after endotoxin administration. Cardiac cytosolic protein kinase C activity was
      increased by 50% (p < 0.05) while the membrane-associated protein kinase C
      activity remained unaltered following endotoxin injection. Cardiac protein kinase
      M activity was decreased by 38.5% (p < 0.01) post endotoxin. In the liver, type I
      protein kinase A activity was unaffected while type II protein kinase A activity
      was decreased by 34% (p < 0.01) following endotoxin injection. Hepatic cytosolic
      and membrane-associated protein kinase C activities were inhibited by 37% (p <
      0.01) and 53% (p < 0.01), respectively, 4 hr postendotoxin. Hepatic protein
      kinase M activity was decreased by 61% (p < 0.01) after endotoxin administration.
      These data indicate that the activities of various protein kinases in the heart
      and liver were modified by endotoxin administration. Since protein kinases
      regulate cell function through phosphorylation of various substrate proteins, a
      modification on protein kinase activities may contribute to the development of
      organ dysfunction in endotoxin shock.

PMID- 8152341
TI  - Chronic nicotine intake decelerates aging of nigrostriatal dopaminergic neurons.
AB  - We have evaluated the effect of chronic nicotine intake on the age-associated
      loss of nigrostriatal dopaminergic neurons. The striatal density of dopamine (D1
      and D2) receptors and DA-uptake sites decreased with age. Concomitant with these
      changes was a pronounced loss of many behavioral functions associated, at least
      in part, with dopaminergic neurotransmission. Chronic oral intake of nicotine
      resulted in partial restoration of the loss of receptors as well as behavioral
      performances. The results suggest that low doses of nicotine could have
      beneficial effects during aging.

PMID- 8152342
TI  - Effects of fructose-1,6-bisphosphate on brain polyamine biosynthesis in a model
      of transient cerebral ischemia.
AB  - We evaluated the effects on cerebral ischemia of a treatment with fructose-1,6
      bisphosphate, a compound known to possess protective effects on acute ischemic
      injury in a variety of different tissues. We investigated the ability of the
      compound, administered either 15 minutes before or 15 minutes after the ischemic
      insult, in reducing the ischemia-induced changes in polyamine brain levels. The
      experiments were performed in adult, chloral hydrate-anesthetized Mongolian
      gerbils that underwent a 15 minutes ligation of the common carotid arteries
      followed by recirculation. Animals were sacrificed 1, 8 and 24 hours and
      immediately after the release of the occlusion. Polyamine brain levels were not
      modified during ischemia. Putrescine began to increase after eight hours from the
      release of the occlusion and we found it significantly increased after 24 hours
      in the hippocampus and striatum. We did not detect any significant changes in
      spermidine brain levels either during ischemia or during recirculation.
      Conversely, spermine appeared to decrease in the hippocampus while it did not
      show changes in striatum and medulla-pons. The activity of ornithine
      decarboxylase, a key enzyme in the biosynthesis of polyamines, resulted enhanced
      at the end of the ischemic period in all the brain regions tested and showed a
      peak at eight hours of recirculation in striatum and hippocampus whereas returned
      to control values in the medulla-pons. Fructose-1,6-bisphosphate significantly
      reduced the ischemia induced changes in polyamine brain content when administered
      before the ischemic insult while did not show protective properties when
      administered post-ischemically.

PMID- 8152343
TI  - Mass determination of the fatty acids released from tannin-stimulated rabbit
      alveolar macrophages.
AB  - Previous studies with macrophages that had been prelabeled with [14C]arachidonic
      acid (20:4) have shown that condensed tannin is a potent agonist for the release
      of arachidonic acid. However, it has not been demonstrated that the percentage
      release of [14C]20:4 accurately reflects the metabolic activity of the endogenous
      20:4 pool. In order to measure the 20:4 mass release relative to the total
      cellular 20:4 pool, the free fatty acids of freshly isolated alveolar macrophages
      were derivatized with a fluorescent reagent, and then separated and quantified by
      high-performance liquid chromatography. The amounts of esterified fatty acids
      were measured by gas chromatography of the methyl esters. Free fatty acid levels
      were compared to those of the total esterified plus unesterified fatty acids to
      determine the actual percentage release of each fatty acid. Tannin-stimulated
      release of 20:4 mass reflected that previously reported for the release of
      [14C]20:4 label but at a slower rate and at a much lower percentage indicating
      that [14C]20:4 had been incorporated into part of a more reactive pool. The
      specificity of the fatty acid release induced by tannin and beta-1,3-glucan, a
      known agonist for 20:4 release, was also examined. Both agonists promoted an
      increase in the levels of free 20:4 and of other fatty acids. A comparison of the
      absolute increases of each of the fatty acids indicated that tannin caused a
      preferential increase in the mass of free 20:4, whereas beta-1,3-glucan evoked a
      selective increase in the mass of 16:0.

PMID- 8152344
TI  - Essential fatty acids alter the activity of manganese-superoxide dismutase in rat
      heart.
AB  - The effects of oil-derived dietary essential fatty acids on the activities of
      mitchondrial Mn-SOD (manganese-superoxide dismutase) and cytosolic cupric zinc
      superoxide dismutase (Cu/Zn-SOD) were investigated in rat heart. A control group
      of rats was fed a stock diet for 29 d, and a second group was fed on a fat-free
      diet. Three other groups were fed fat-free diets that were supplemented with (i)
      borage oil, which is rich in linoleic (18:2n-6) and gamma-linolenic (18:3n-6)
      acids, (ii) fungal oil, which is rich in gamma-linolenic, but low in linoleic
      acid, or (iii) evening primrose oil, which is rich in linoleic acid and low in
      gamma-linolenic acid. An increase in the percentage composition of arachidonic
      acid (20:4n-6) in both the choline and ethanolamine phospholipids, together with
      a decrease in linoleic acid in ethanolamine phospholipids, were found in heart
      membranes after feeding the rats with diets containing borage oil or fungal oil
      as compared to those fed the stock diet. The respective activities of Mn-SOD in
      rats fed the borage or fungal oil diets were also significantly higher than in
      rats fed the stock diet alone. No change in cytosolic Cn/Zn-SOD activity was
      observed. Dietary supply of linoleic acid-rich evening primrose oil resulted in
      an increased proportion of choline phospholipid linoleic acid without any changes
      in arachidonic acid content or in the activity of Mn-SOD. By contrast, a
      reduction in the activity of Mn-SOD was detected in rats fed a fat-free
      diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152345
TI  - Gradient for D-glucose and linoleic acid uptake along the crypt-villus axis of
      rabbit jejunal brush border membrane vesicles.
AB  - Glucose uptake into jejunal brush border membrane (BBM) varies along the crypt
      villus axis (CVA). In the present study, the question was addressed whether
      uptake of the essential long-chain fatty acid linoleic acid also varies along the
      CVA. Using agitation techniques, five jejunal enterocyte fractions were
      sequentially isolated from female New Zealand white rabbits. A sixth and final
      fraction of lower-villus/crypt cells was obtained by the scraping of the
      remaining jejunal mucosa. Cell fraction along the CVA was proven histologically,
      by noting decreasing alkaline phosphatase activities in sequentially isolated
      fractions, and by demonstrating [3H-methyl]thymidine uptake mainly in the final
      fraction of the lower villus/crypt cells. BBM vesicles were prepared from the
      upper, mid- and lower-villus/crypt enterocyte fractions, using differential
      centrifugation and divalent ion precipitation. D-Glucose uptake into each
      fraction showed an Na(+)-gradient dependent time-course "overshoot" with linear
      uptake to 15 s and a subsequent decline to a steady-state plateau. Varying D
      glucose concentrations from 50-1000 microM demonstrated saturation kinetics of
      uptake, with maximal transport rates (Vmax) and Michaelis affinity constants (Km)
      varying between fractions; the Km and Vmax were both lowest in the upper-villus
      fraction. A linear relationship existed between linoleic acid concentration (25
      200 microM) and uptake in each fraction. Linoleic acid uptake was equivalent in
      all fractions when expressed per mg protein, but when expressed in terms of the
      estimated minimal BBM, vesicle surface area uptake was greater in the upper- than
      in the lower-villus/crypt fractions. Thus, BBM vesicle uptake of both linoleic
      acid and glucose vary along the crypt-villus axis of the rabbit jejunum.

PMID- 8152347
TI  - Interactions between medium-chain and long-chain triacylglycerols in lipid and
      energy metabolism in growing chicks.
AB  - The combined effects of dietary medium-chain triacylglycerols (MCT) and long
      chain triacylglycerols (LCT) on lipid and energy utilization in chicks were
      investigated. Corn oil was used as the LCT source, and trioctanoin (8:0) was used
      as the MCT source. The efficiency of dietary energy utilization (such as
      metabolizable energy values and fat and energy retention) decreased linearly as
      the level of MCT increased, but the efficiency of dietary protein utilization
      (protein retained per protein consumed) was not affected in a consistent manner.
      Fecal saturated and monounsaturated fatty acid composition was dependent on the
      dietary fatty acid composition, whereas fecal linoleic acid content was not. It
      is concluded that dietary MCT and LCT influence each other to some degree, with
      respect to protein and lipid metabolism in chicks. Moreover, in most cases, the
      nutritional characteristics of each triacylglycerol, including food efficiency
      and fat and energy retention, are independent of each other in growing chicks.

PMID- 8152346
TI  - The effect of dietary fat level and quality on plasma lipoprotein lipids and
      plasma fatty acids in normocholesterolemic subjects.
AB  - This study examined the effect on the plasma lipids and plasma phospholipid and
      cholesteryl ester fatty acids of changing froma typical western diet to a very
      low fat (VLF) vegetarian diet containing one egg/day. The effect of the addition
      of saturated, monounsaturated or polyunsaturated fat (PUFA) to the VLF diet was
      also examined. Three groups of 10 subjects (6 women, 4 men) were fed the VLF diet
      (10% energy as fat) for two weeks, and then in the next two weeks the dietary fat
      in each group was increased by 10% energy/week using butter, olive oil or
      safflower oil. The fat replaced dietary carbohydrate. The VLF diet reduced both
      the low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol
      levels; addition of the monounsaturated fats and PUFA increased the HDL
      cholesterol levels, whereas butter increased the cholesterol levels in both the
      LDL- and HDL-fractions. The VLF diet led to significant reductions in the
      proportion of linoleic acid (18:2 omega 6) and eicosapentaenoic acid (20:5 omega
      3) and to increases in palmitoleic (16:1), eicosatrienoic (20:3 omega 6) and
      arachidonic acids (20:4 omega 6) in both phospholipids and cholesteryl esters.
      Addition of butter reversed the changes seen on the VLF diet, with the exception
      of 16:1, which remained elevated. Addition of olive oil resulted in a significant
      rise in the proportion of 18:1 and significant decreases in all omega 3 PUFA
      except 22:6 compared with the usual diet. The addition of safflower oil resulted
      in significant increases in 18:2 and 20:4 omega 6 and significant decreases in
      18:1, 20:5 omega 3 and 22:5 omega 3. These results indicate that the reduction of
      saturated fat content of the diet (< 6% dietary energy), either by reducing the
      total fat content of the diet or by exchanging saturated fat with unsaturated
      fat, reduced the total plasma cholesterol levels by approximately 12% in
      normocholesterolemic subjects. Although the VLF vegetarian diet reduced both LDL-
      and HDL-cholesterol levels, the long-term effects of VLF diets are unlikely to be
      deleterious since populations which habitually consume these diets have low rates
      of coronary heart disease. The addition of safflower oil or olive oil to a VLF
      diet produced favorable changes in the lipoprotein lipid profile compared with
      the addition of butter. The VLF diets and diets rich in butter, olive oil or
      safflower oil had different effects on the 20 carbon eicosanoid precursor fatty
      acids in the plasma.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8152348
TI  - The acute effects of a single very high dose of n-3 fatty acids on plasma lipids
      and lipoproteins in healthy subjects.
AB  - Forty healthy volunteers were allocated in a double blind, randomized study to
      receive either 20 g of n-3 polyunsaturated fatty acids (PUFA) or 20 g of n-6 PUFA
      at their evening meal. The effect on plasma lipids and lipoproteins of this
      single dose of fish oil vs. corn oil was studied the next morning, 14 h after
      ingestion. Plasma triglycerides and very low density lipoprotein-cholesterol
      significantly decreased (33%) after n-3 PUFA (P < 0.001), and significantly (P <
      0.01) more than after intake of n-6 PUFA. The decrease in plasma triglycerides
      after n-3 PUFA ingestion was more pronounced in subjects with higher baseline
      levels of triglycerides (P < 0.001). Total cholesterol decreased after both
      supplements, but did not differ between the supplements. Low density lipoprotein
      cholesterol did not change, and high density lipoprotein-cholesterol
      significantly decreased in subjects given n-3 PUFA compared to baseline, but not
      when compared to subjects receiving n-6 PUFA. In conclusion, we have shown that a
      single very high dose of n-3 PUFA has a pronounced hypotriglyceridemic effect,
      which is directly related to the initial plasma level.

PMID- 8152349
TI  - Singlet oxygen quenching ability of naturally occurring carotenoids.
AB  - The singlet oxygen quenching ability of various naturally occurring carotenoids
      was examined by measuring toluidine blue-sensitized photooxidation of linoleic
      aci. To assess quenching, the oxidation of linoleic acid was followed by
      measuring oxygen consumption and ultraviolet absorbance at 235 nm. We found that
      oxygen quenching increased as the number of conjugated double bonds in the
      carotenoids increased, but quenching varied with chain structure and functional
      groups. Acyclic carotenoids enhanced quenching more than did cyclic carotenoids.
      Conjugated keto groups and the presence of a cyclopentane ring stimulated
      quenching, while hydroxy, epoxy and methoxy groups showed lesser effects. The
      photosynthetic bacterial carotenoids, spirilloxanthin and rhodopin, were found to
      be most effective as quenchers, followed by the cayenne carotenoid, capsorbin.

PMID- 8152350
TI  - Synthesis of a phosphatidyl derivative of vitamin E and its antioxidant activity
      in phospholipid bilayers.
AB  - A novel phospholipid containing a chromanol structure at its polar head group was
      synthesized from egg yolk phosphatidylcholine and 2,5,7,8-tetramethyl-6-hydroxy-2
      (hydroxyethyl)chroman by transphosphatidylation catalyzed by phospholipase D from
      Streptomyces lydicus. The structure of the product synthesized was shown by
      spectral analysis to be 1,2-diacyl-sn-glycero-3-phospho-2'-hydroxyethyl-
      2',5',7',8'-tetramethyl-6'-hydroxychroman. The phosphatidylchromanol (PCh) showed
      antioxidant activity against radical chain oxidation of methyl linoleate in
      solution in a manner similar to that of d-alpha-tocopherol (alpha-Toc) and
      2,2,5,7,8-pentamethyl-6-chromanol. However, PCh was less effective as a chain
      breaking antioxidant than was alpha-Toc when unilamellar egg yolk
      phosphatidylcholine liposomes were exposed to either a water-soluble or a lipid
      soluble radical initiator. It is likely that the phospholipid nature of PCh
      affects the location and the mobility of the chromanol moiety in the membrane
      bilayer resulting in a decrease in antioxidant activity. On the other hand, the
      antioxidant activity of PCh was little different from that of alpha-Toc in
      unilamellar liposomes when exposed to a lipid-soluble radical initiator in the
      presence of ascorbic acid. It appears that PCh in phospholipid bilayers can be
      regenerated by ascorbic acid in aqueous phase as can be alpha-Toc. The new
      phospholipid, phosphatidylchromanol, should prove useful as a chain-breaking
      antioxidant in phospholipid membranes.

PMID- 8152351
TI  - Butylated hydroxyanisole inhibits tumor necrosis factor-induced cytotoxicity and
      arachidonic acid release.
AB  - The mechanisms by which the antioxidant butylated hydroxyanisole (BHA) inhibits
      recombinant tumor necrosis factor alpha (rTNF-alpha)-induced cytotoxicity have
      been studied in WEHI 164 clone 13 (WEHI) and L929 fibrosarcoma cells. When BHA
      was added simultaneously with rTNF-alpha, it completely inhibited rTNF-alpha
      cytotoxicity in the WEHI and L929 cells. BHA also inhibited the toxicity when
      added 2 h after rTNF-alpha in WEHI cells, suggesting that BHA inhibits some late
      intracellular event(s) in rTNF-alpha cytotoxicity. Pretreating WEHI cells with
      BHA for 4 h did not decrease the binding of rTNF-alpha to its receptors as
      measured using flow cytometry. BHA inhibited rTNF-alpha toxicity in the presence
      of actinomycin D and cycloheximide, indicating that neither mRNA nor protein
      synthesis is necessary for the BHA effect. The antioxidant butylated
      hydroxytoluene (BHT) and indomethacin did not inhibit the rTNF-alpha-induced
      cytotoxicity nor the rTNF-alpha-induced release of [3H]arachidonic acid. By
      comparison, BHA completely inhibited the rTNF-alpha-induced release of
      arachidonic acid, suggesting that BHA somehow inhibits rTNF-alpha-induced
      activation of phospholipase(s). In WEHI cells, rTNF-alpha increased the level of
      protein-associated thiobarbituric acid reactive substances (TBARS) dose
      dependently. BHA, but not BHT, blocked rTNF-alpha-induced cytotoxicity and rTNF
      alpha-induced accumulation of protein-associated TBARS, suggesting that rTNF
      alpha cytotoxicity is correlated with protein-associated TBARS. In conclusion,
      the results suggest that BHA blocks some post receptor event in rTNF-alpha
      induced cytotoxicity, and that activation of phospholipase(s) coupled with the
      enzymatic formation of specific oxidized lipids could be a pivotal event in rTNF
      alpha-induced cytotoxicity.

PMID- 8152352
TI  - Isoniazid prophylaxis: the importance of individual values.
AB  - To provide insight into the decision whether to use isoniazid prophylaxis in
      uncomplicated cases of positive tuberculin tests, the authors conducted a
      multicriteria decision analysis using the analytic hierarchy process. If reducing
      the chance of developing active tuberculosis is considered at least slightly more
      important than avoiding isoniazid-related side effects, isoniazid prophylaxis is
      the better strategy for all patients. If avoiding isoniazid-related side effects
      is considered at least slightly more important, no prophylaxis is the better
      strategy for all patients. If these two considerations are judged equally
      important, the better strategy depends on patient age, the anticipated
      effectiveness of isoniazid prophylaxis, and whether or not the patient is a
      recent tuberculin convertor. The tradeoff between avoiding active tuberculosis
      and avoiding isoniazid-related side effects is the most important factor in the
      decision regarding the proper management of patients with positive tuberculin
      tests. These results emphasize the importance of taking an individualized
      approach to the management of these patients.

PMID- 8152353
TI  - Global judgments versus decision-model-facilitated judgments: are experts
      internally consistent?
AB  - A widely used method for evaluating the appropriateness of medical procedures and
      practices is the "modified Delphi" approach using expert panelists' global
      ratings. However, several difficulties in the assignment of global ratings have
      led to a search for alternative methods, including the use of decision models. To
      examine the potential impact of using decision models with an expert panel, the
      authors compared a panel's global ratings for the appropriateness of carotid
      endarterectomy with the results of a decision-analytic model in which expert
      panelists estimated probabilities and utilities that were used as inputs for the
      model. For 17 different patient scenarios, the nine expert panelists showed
      variability in "calibration" between the two methods, with their expected
      utilities calculated from the model generally being higher than their global
      ratings. However, the correlation between the two methods was excellent. When the
      panel's median global utility was compared with the panel's median expected
      utility calculated from the model, the Spearman correlation coefficient was 0.88.
      This study demonstrated that an expert panel's appropriateness ratings and their
      expected utilities were highly correlated. In addition, the panelists appeared to
      be internally consistent in that their judgments about individual probabilities
      and utilities were correlated with their global judgments. These results should
      encourage additional efforts to incorporate decision models into the process of
      clinical guideline development. The authors believe that decision models can help
      improve a panel's capacity to understand and reconcile discordance, and increase
      their satisfaction that the process reflects the best possible judgments.

PMID- 8152354
TI  - An architecture for knowledge-based construction of decision models.
AB  - Clinical application of decision analysis has been limited by unfamiliarity of
      clinicians with the technique, large data requirements, and the length of time
      needed to construct models. In order to make decision modeling more accessible to
      clinicians, the authors developed a computer program to construct decision models
      automatically. The system contains two separate knowledge bases. One contains
      frames encoding knowledge of the medical domain, the evaluation of pulmonary
      disease in patients infected with the human immunodeficiency virus (HIV). The
      other contains rules of correct decision model construction that guide the
      selection of items from the domain knowledge base and their insertion into the
      decision model. The system can create either a tree or an influence diagram that
      satisfies previously published critiquing rules. The system has the potential to
      enable novices to construct useful decision models and to provide individualized
      decision-analytic advice to clinicians in real time.

PMID- 8152355
TI  - Nurses' fear of contagion: a functional-measurement analysis.
AB  - The amounts of fear of contagion aroused in nurses by 15 unnamed diseases were
      examined. The diseases were chosen to allow factorial arrangement according to
      their degrees of transmissibility and the severities of their prognoses. Concern
      about contagion was hypothesized to increase as transmissibility increased and as
      prognosis worsened, in accord with a multiplicative model. The model was tested
      with functional measurement procedures, because this method allows simultaneous
      evaluation of the descriptive accuracy of the proposed model and validation of
      the rating scale. The model was supported graphically and statistically. Nurses'
      worries were found to have the regularity prescribed by a multiplicative process.
      Although one of the diseases was constructed to simulate the characteristics of
      AIDS, no magnification of fear was found in relation to other deadly and
      infectious diseases.

PMID- 8152356
TI  - Uncertainty in Bayes.
AB  - Most standard discussions of Bayes' formula treat sensitivity, specificity, and
      the prior probability as fixed parameters for probability revision, but in fact
      these usually have associated variability. This in turn generates predictable
      patterns of uncertainty in the posterior probabilities. Although these have not
      been investigated in detail, they have important implications for the
      interpretation of posterior probabilities and the clinical use of Bayesian
      probability revision. For a test with a high likelihood ratio for a positive
      result, the positive predictive value (PPV) is strongly affected by uncertainties
      in the prior probability when the prior probability is small, but PPV is almost
      independent of such uncertainties at high values of the prior probability. The
      PPV is more affected by changes in specificity than by changes in sensitivity,
      and uncertainty in specificity has its maximal impact on the PPV at low prior
      probability values. These patterns are most pronounced for tests with high
      likelihood ratios of positive results. Similar results can be shown for the
      negative predictive value. These results imply that for suitability good tests,
      probability revision in certain definable ranges of prior probability may be so
      strongly affected by errors in the estimations of both the prior probability and
      the operating characteristics that the posterior probabilities may be unstable in
      practice. On the other hand, at other values of the prior probability, the
      posterior probabilities are almost constant, and formal probability revision will
      not have much impact. These patterns indicate limitations to the reliability and
      usefulness of calculated posterior probabilities, and have important implications
      for the clinical use of Bayes' formula.

PMID- 8152357
TI  - Determining transition probabilities: confusion and suggestions.
AB  - Confusion regarding proper use of the terms rate and risk persists in the
      literature. This has implications for the proper modeling of prognosis and
      transition between health states in decision analysis and related techniques. The
      issue is complicated by the plethora of terms related to rate and risk. Although
      the suggestion to use the terms force and probability as substitutes for rate and
      risk has some appeal, the change in terminology by itself is unlikely to solve
      all the confusion or misuse of terms. This paper clarifies the proper definitions
      and estimations of rates and risks and suggests critical factors for the decision
      analyst to remember when using, modeling, or interpreting transition rates and
      risks.

PMID- 8152358
TI  - Meta-analysis of failure-time data with adjustment for covariates.
AB  - The objective of this study was to present and illustrate a technique for
      combining failure-time data from various sources, adjusting for differences in
      case-mix among studies. Based on the proportional-hazards model and the actuarial
      life-table approach, the method used assumes that the variation across studies is
      in part due to heterogeneity of the case-mix and adjusts for the case-mix before
      pooling results. As an example, the technique is applied to life-table data from
      six selected papers reporting patency of affected arteries following
      femoropopliteal angioplasty. Published 4- and 5-year patency results ranged from
      25% to 58%, with a pooled five-year cumulative patency rate (without adjustment
      for case-mix) of 45% (+/- 2%). The populations in these studies, however,
      differed markedly in the prevalence of factors with prognostic value: type of
      lesion and distal runoff vessels. After adjustment for these differences in case
      mix, the pooled five-year patency rates ranged from 60% (+/- 2%) for patients
      with stenotic lesions and good runoff to 24% (+/- 9%) for those with occlusion
      and poor runoff. The authors conclude that pooling studies without considering
      the effect of case-mix yields an average result with inappropriately narrow
      confidence intervals that does not reflect the variability across subgroups. The
      presented technique provides a method for combining failure-time data, adjusting
      for case-mix.

PMID- 8152359
TI  - Patency results of percutaneous and surgical revascularization for
      femoropopliteal arterial disease.
AB  - To estimate the patency results of percutaneous transluminal angioplasty and
      bypass surgery in the treatment of femoropopliteal arterial disease, a Medlars
      search of the English-language medical literature was performed. Inclusion
      required that studies 1) report original data, 2) report patency with a life
      table or Kaplan-Meier analysis with the number at risk or standard errors, 3)
      define patency as hemodynamic improvement, 4) report the distribution of
      covariates, and 5) not duplicate other published material. Using a method based
      on the proportional-hazards model and the actuarial life-table approach, the
      results were adjusted for differences in case-mix of the study populations and
      patency was predicted for subgroups at various levels of risk for failure. The
      unadjusted pooled life tables yielded five-year patencies of 45% (+/- 2%) for
      angioplasty, 73% (+/- 2%) for bypass surgery using a vein graft, and 49% (+/- 3%)
      for bypass surgery using a polytetrafluoroethylene graft. Adjusted five-year
      primary patencies after angioplasty varied from 12% to 68%, the best results
      being for patients with claudication and stenotic lesions. Adjusted five-year
      primary patencies after surgery varied from 33% to 80%, the best results being
      for saphenous vein bypass performed for claudication. The authors conclude that
      pooling life-table data without adjustment for covariates can be misleading.
      Indication, lesion type, vein graft availability, and site of the distal graft
      anastomosis need to be considered in predicting patency results of
      revascularization for femoropopliteal arterial disease.

PMID- 8152360
TI  - Utility assessment in cancer patients: adjustment of time tradeoff scores for the
      utility of life years and comparison with standard gamble scores.
AB  - The standard gamble (SG) and the time tradeoff (TTO), two frequently used methods
      of utility assessment, have often been found to lead to different utilities for
      the same health state. The authors investigated whether adjustment of TTO scores
      for the utility of life years (risk attitude) eliminated this difference. In
      addition, the association between risk attitude and sociodemographic and medical
      variables was studied. In 30 disease-free testicular cancer patients, SG and TTO
      were used to assess the utilities of four health profiles relevant to testicular
      cancer. Utility of life years was estimated from certainty equivalents (CEs). SG
      scores were significantly higher than unadjusted TTO scores for all profiles. As
      the majority of patients (85%) were risk-averse, CE-adjusted TTO scores were
      higher than unadjusted scores, and were not significantly different from those
      obtained from the SG for three of the four profiles. However, adjusted scores
      were still slightly but consistently lower than SG scores. Possible explanations
      for this discrepancy are discussed. An association was found between risk
      aversion and medical treatment: patients who had received chemotherapy for their
      cancers were more risk-averse than were patients who had been in a surveillance
      protocol only. As risk aversion can have an impact on treatment decisions, it is
      important to assess the risk posture of the patient to whom the decision
      pertains.

PMID- 8152361
TI  - Measuring preferences for health states worse than death.
AB  - Previous research indicates that persons assigning values to ranges of health
      states consider some states to be worse than death. In a study of decisions
      regarding life-sustaining treatments, the authors adapted and assessed existing
      methods for their ability to identify and quantify preferences for health states
      near to or worse than death in a population of well adults and nursing home
      residents. The cognitive burdens involved in these decisions were also evaluated.
      Hypothetical health states based on six attributes of functional status were
      constructed to describe severe constant pain, dementia, and coma. The methods of
      rank order, category scaling, time tradeoff, and standard gamble were adapted to
      quantify states worse than death. Cognitive burden was assessed using completion
      rates, interviewer assessments, respondents' self-reporting, and investigators'
      evaluations. For both respondent groups, all methods showed similar degrees of
      cognitive burden for those able to complete the tasks and were similar in their
      ability to identify and quantify preferences. The majority of nursing home
      residents, however, were unable to complete or comprehend the measurement tasks.
      Most respondents evaluated their current health and severe constant pain as
      better than death; dementia and coma were more often considered equal to or worse
      than death. These results indicate that respondents can and do evaluate some
      health states as worse than death. The authors recommend systematic inclusion of
      states worse than death to describe a more complete range of preference values
      and routine assessment of the cognitive burdens of assessment techniques to
      evaluate methodologies.

PMID- 8152362
TI  - Content of a decision analysis for treatment choice in end-stage renal disease:
      who should be consulted?
AB  - For an illness whose treatment options lead to similar survival, quality-of-life
      issues determine the choice. If the patient has not yet experienced the
      treatments, then the information provided regarding the options plays a crucial
      role in the patient's choice. The authors interviewed 43 people who are
      intimately involved with the treatments for end-stage renal disease (ESRD) (ten
      physicians, 11 nurses, and 22 patients) with a view to determining what
      information needs to be considered when choosing between the various treatment
      options for this illness. They compared the three groups based on the items
      obtained from the interviews to determine whether the inclusion of patients in
      the process changed the content of the treatment descriptions. They were also
      interested in determining whether the use of the frequency with which an item is
      mentioned in the interviews is a valid measure of its relative importance to
      other items. 1,269 relevant items were obtained from the interviews and
      categorized into 51 areas of concern (subject domains). The health professionals
      (physicians and nurses) were found to have mentioned seven subject domains more
      often than the patients, and no domain was mentioned more often by the patients
      than by the health professionals. The frequency that an item was mentioned was
      correlated (r = 0.55) with direct measures of its importance. These results imply
      that careful consultation with health professionals to determine the content of a
      decision analysis or informational materials that address treatment choice is
      sufficient to address patient concerns and that items can be chosen for inclusion
      based on the relative frequencies with which they are mentioned.

PMID- 8152363
TI  - DEALE-ing and discounting: a simple way to compute the accrued costs of
      preventive strategies.
AB  - Researchers agree on the importance of discounting costs and of including
      mortality rates in the cost computations. The authors present a simplified
      mathematical model that allows both DEALE-ing and discounting and permits easy
      computations of accrued and incremental costs. The general formula of the accrued
      discounted cost of treating over time of life expectancy is: C = Co/mu asr + mu D
      + i A systematic discussion of the errors involved in the DEALE approximation
      shows that it will in most cases truly describe the ordering of the costs of
      various treatments. The DEALE are compared with the costs obtained by using
      actual mortality statistics. It was found that when two strategies have actual
      costs CA and CB such as CA greater than CB and CA/CB superior to 1.25, the
      ordering of CA and CB will always be kept in this simplified model.

PMID- 8152364
TI  - Isolation of mycobacteria in patients with pulmonary alveolar proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by
      accumulation of proteinaceous material in the alveoli of affected individuals.
      Pulmonary infections appear to develop with increased frequency in these
      patients. The increased rate of infection has been attributed to immunologic
      aberrations, such as impaired alveolar macrophage function, particularly when
      uncommon pathogens are involved. Among those pathogens, Nocardia asteroides and
      Mycobacterium tuberculosis have appeared most often in case reports in the
      literature. Mycobacterium avium-intracellulare (MAI) has rarely been isolated in
      these patients. We report an unusually high incidence of MAI isolation from
      lavage fluid in 8 of 19 consecutive patients who underwent therapeutic lung
      lavage for relief of symptomatic PAP, and summarize the available literature on
      isolation of potential respiratory pathogens in PAP.

PMID- 8152365
TI  - Central nervous system lesions in adult liver transplant recipients: clinical
      review with implications for management.
AB  - Our review shows that a wide array of neurologic complications can occur after
      liver transplantation. Clinical correlation of the neuropathologic lesions may be
      difficult, as multiple lesions of variable etiologies may coexist, and
      significant systemic and metabolic complications may obscure the symptoms related
      to an underlying lesion in the central nervous system. Nevertheless, a reasoned
      approach to the recognition and diagnosis of these lesions is offered. In the
      early post-transplantation period, noninfectious lesions predominated. Of these,
      anoxic-ischemic changes and vascular events (hemorrhages and/or infarcts)
      occurred most frequently. Anoxic events occurred a mean of 10 days after
      transplantation and were often preceded by transient or varying degrees of
      hypotension. Hemorrhagic events and infarcts occurred a median of 27 and 5 days,
      respectively, after transplantation. It should be noted, however, that the
      projected onset of these events may vary somewhat, e.g., a brain infarct
      developed 47 days after liver transplantation in case 2. Although defects in
      coagulation may predispose to hemorrhagic lesions, a source for the infarct is
      usually not apparent. Central pontine myelinolysis is also an early-occurring
      lesion: most cases are seen within 10 days of transplantation. Extrapontine
      involvement frequently coexisted with or was present without pontine lesions.
      Hyponatremia or wide variations in serum sodium generally preceded the CNS
      lesion. Focal areas of high signal density by CT scan in the pons was highly
      suggestive of central pontine myelinolysis. Cyclosporine may cause white matter
      changes in the brain despite normal serum cyclosporine levels.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8152366
TI  - Fungal sinusitis in patients with AIDS: report of 4 cases and review of the
      literature.
AB  - We report here 3 cases of aspergillus sinusitis in patients with AIDS and the 1st
      fully described case, to our knowledge, of sinusitis associated with
      Pseudallescheria boydii in a patient with AIDS. We review the microbiology and
      pathology of fungal sinusitis in patients with AIDS and the morphologic and
      clinical features and treatment of P. boydii infection and aspergillus sinusitis.
      Fungal sinusitis in patients with HIV or AIDS generally occurs later in the
      course of primary disease with low CD4+ lymphocyte counts (< 50/mm3), unlike
      bacterial sinusitis which may occur at any time. Differentiation between invasive
      and noninvasive forms is likely not important, in contrast to fungal sinusitis in
      noncompromised patients. The number of cases is likely to increase as the number
      of patients with AIDS increases, patients survive longer, and other opportunistic
      infections are prevented or treated. Causative agents are likely to be resistant
      to fluconazole, which is in widespread use. Aspergillus sinusitis in patients
      with HIV or AIDS occurs in both those with and without traditional risk factors.
      Fungal sinusitis may present vexing management problems and be relentlessly
      progressive in the face of therapy. Ideal therapy has yet to be defined but an
      early combined surgical and medical approach in these compromised patients is
      preferred.

PMID- 8152367
TI  - IgA nephropathy: analysis of the natural history, important factors in the
      progression of renal disease, and a review of the literature.
AB  - To clarify the natural history of IgA nephropathy and to determine important
      factors in the progressive loss of renal function in affected patients, 121
      patients with IgA nephropathy were followed for a median of 92 months. The
      cumulative probability of not progressing to end-stage renal failure (that is, of
      renal survival) was 0.87 at 15 years after the onset of 1st symptoms and 0.86 at
      10 years after presentation and biopsy. Eight percent of patients progressed to
      end-stage renal failure, and 12% had a greater than 20% decline in renal
      function. A complete remission of disease activity was seen in 12% of patients,
      and the remaining 68% maintained stable renal function. When the final serum
      creatinine was expressed as a percentage of the initial serum creatinine for each
      patient and compared with all other variables, a number of factors were found to
      affect renal outcome. Of the presenting features, increased age, family history
      of nephritis, longer duration of symptoms, and presence of either nephrotic-range
      proteinuria or hypertension were all associated, by univariate analysis, with an
      adverse outcome, while a history of recurrent macroscopic hematuria and infection
      associated exacerbations of disease activity were associated with a favorable
      outcome. Multivariate analysis showed that nephrotic-range proteinuria had an
      independent adverse effect. Of the initial laboratory findings, by univariate
      analysis, the number of hyaline casts, the degree of impairment of renal
      function, the degree of proteinuria, raised beta globulins on serum protein
      electrophoresis, and serum C4 concentrations were all associated with an adverse
      outcome, while the severity of initial hematuria and pyuria were associated with
      a favorable outcome. Renal biopsy findings associated with an adverse outcome by
      univariate analysis include, on light microscopy, the percentage of glomeruli
      with global sclerosis or segmental sclerosis or adhesions, the degrees of tubular
      atrophy or interstitial fibrosis, interstitial inflammation and blood-vessel
      thickening, and, on immunofluorescence, the intensity of IgA deposition.
      Multivariate analysis showed independent adverse effects on renal outcome of
      global glomerulosclerosis, segmental glomerulosclerosis or adhesions, and a
      combined mesangial and capillary wall deposition of IgM. Features at final
      assessment or during follow-up associated with an adverse outcome include, by
      univariate analysis, the number of hyaline casts, the degree of impairment of
      renal function, the degree of proteinuria, reduced serum IgG and IGM
      concentrations, reduced final IgA expressed as a percentage of the initial IgA
      concentration, transient decreases of creatinine clearance during follow-up of >
      10% or > 20%, and persistence or development of hypertension.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8152368
TI  - Halobacterial megaplasmids are negatively supercoiled.
AB  - Several covalently closed circular halobacterial megaplasmids (up to more than
      500 kb) from different strains of Haloferax mediterranei, have been resolved by
      orthogonal-field alternating gel electrophoresis (OFAGE). These molecules seem to
      be negatively supercoiled in vivo, as deduced from the effect of intercalating
      agents affecting their topology and, therefore, their electrophoretic mobility.
      It has also been demonstrated that the topoisomerase II inhibitor novobiocin
      affects the native topological state of halobacterial megaplasmids impeding their
      migration in OFAGE under standard conditions for resolution of large supercoiled
      molecules.

PMID- 8152369
TI  - Initiation and termination of DNA transfer at F plasmid oriT.
AB  - DNA sequences within the F plasmid transfer origin (oriT) were tested for their
      ability to initiate or terminate conjugal transfer. Mutant and wild-type oriT
      elements were cloned as direct repetitions flanking the rpsL gene on a pBR322
      based plasmid, and the frequency of deletion of this segment during matings
      sponsored by F'lac (F42) with streptomycin-resistant recipients was measured.
      Shortened oriT elements that lacked adjacent TraM-binding sites allowed efficient
      initiation and termination. Some truncated oriT segments lacking the TraM-binding
      sites and the TraY-binding site, sbyA, initiated transfer inefficiently, but
      nevertheless promoted efficient termination. Removal of TraM-, TraY-, and IHF
      binding sites severely reduced both nicking and termination. Point mutations that
      previously had been reported to prevent nicking caused reduced levels of both
      initiation and termination. These results indicate that regions of oriT
      supporting initiation are more extensive than those needed for termination,
      although some regions are required for both. Moreover, termination can be
      effective for some mutant loci that do not support efficient nicking.

PMID- 8152370
TI  - Mutational and physical analysis of F plasmid traY protein binding to oriT.
AB  - F plasmid traY protein binding to wild-type or deleted regions containing the
      TraY-binding site, sbyA, was studied in vitro. The principal DNA-protein complex
      was formed with DNA segments including the sbyA site defined by footprinting and
      (with lesser affinity) with truncated segments that retained the leftward two
      thirds of sbyA. This located the major sequence determinants for TraY binding
      between bp 204 and 227 on the oriT map. For all sequences tested, bound TraY
      induced bending of approximately 50 to 55 degrees, and centred between bp 214 and
      221. Thermodynamic and mobility analyses indicated that two TraY protomers bind
      to sbyA. At higher TraY concentrations, additional TraY bound to the left of the
      sbyA in a region previously shown to bind IHF (site IHF A). TraY binding to this
      additional site (sbyC) was inhibited by IHF. Sequence similarities shared by
      sbyA, sbyB, and sbyC may include the critical base pairs for TraY binding.

PMID- 8152371
TI  - Bacillus anthracis pXO1 virulence plasmid encodes a type 1 DNA topoisomerase.
AB  - The virulence plasmid pXO1 is responsible for toxin production in Bacillus
      anthracis. A DNA fragment from pXO1 was isolated and was shown, by sequence
      analysis, to contain part of a type 1 DNA topoisomerase gene. Attempts to clone
      the entire wild-type gene, designated topX, in Escherichia coli, were
      unsuccessful. In order to obtain the complete gene, it was first insertionally
      inactivated and then cloned in the mutated form. The deduced amino acid sequence
      of Topo X1 shows similarities to that of the two E. coli type 1 DNA
      topoisomerases. The N-terminal two-thirds of the putative B. anthracis protein
      exhibits strongest sequence similarity to topoisomerase III, whereas the C
      terminal portion contains cysteine residues that could form three zinc-binding
      domains, as they do in topoisomerase I. The suggested active-site tyrosine is
      conserved in all three proteins. The regulation of expression from the topX
      promoter is modified by addition of a gyrase inhibiting antibiotic. The Topo X1
      protein is likely to be involved in the stability of pXO1.

PMID- 8152372
TI  - Increased substitution of phosphate groups in lipopolysaccharides and lipid A of
      the polymyxin-resistant pmrA mutants of Salmonella typhimurium: a 31P-NMR study.
AB  - De-O-acylated lipopolysaccharides (LPS) of three polymyxin-resistant Salmonella
      typhimurium pmrA mutants and their parent strains were analysed by 31P-NMR
      (nuclear magnetic resonance) in order to assess, in relation to polymyxin
      resistance, the types and degree of substitution of phosphates of the LPS and
      lipid A. In the pmrA mutant LPS phosphate diesters predominated over phosphate
      monoesters, whereas the latter were more abundant in the parent wild-type LPS.
      The increase in the proportion of phosphate diesters was traced to both the core
      oligosaccharide and the lipid A part. In the latter, the ester-linked phosphate
      at position 4' was to a large extent (79-88%) substituted with 4-amino-4-deoxy-L
      arabinose, whereas in the wild-type LPS the 4'-phosphate was mainly present as
      monoester. In each LPS, regardless of the pmrA mutation, the glycosidically
      linked phosphate of lipid A was largely unsubstituted.

PMID- 8152373
TI  - VsrA, a second two-component sensor regulating virulence genes of Pseudomonas
      solanacearum.
AB  - The wilt-inducing phytopathogen Pseudomonas solanacearum produces several
      extracellular virulence factors, both polysaccharides (EPS I) and proteins
      (EXPs), which are independently regulated by a LysR-type transcriptional
      regulator, PhcA, and a histidine kinase sensor, VsrB. Here we characterize a
      third locus, vsrA, which is also required for normal production of EPS I, some
      EXPs and wilt disease. Analysis of eps::lacZ reporters in vsrA mutants showed
      that, like vsrB and phcA, vsrA is required for maximal expression (transcription)
      of eps, which contains some of the genes necessary for production of EPS I.
      Unlike vsrB and phcA mutants, however, eps transcription (and EPS I production)
      by vsrA mutants varies from 3 to 17% of wild-type levels, depending on growth
      conditions. Inactivation of vsrA also causes a dramatic reduction in production
      of three species of EXPs (28 kDa, 48 kDa, and 66 kDa), and an apparent increase
      in production of a few other EXPs. Unlike most other EPS-deficient P.
      solanacearum strains, vsrA mutants caused almost no disease symptoms when 10(4)
      cells were stem-inoculated into tomato plants. This correlated with a greater
      than 10-fold reduction in their ability to grow in planta. vsrA was cloned from a
      P. solanacearum genomic library by complementation of the vsrA mutant and was
      further subcloned on a 2.3 kb DNA fragment. PhoA fusion analysis and subcellular
      localization of the vsrA gene product in Escherichia coli maxicells suggest that
      it is a 53 kDa membrane-associated protein. Analysis of the nucleotide sequence
      of vsrA revealed a 502 residue open reading frame with homology to the histidine
      kinase domain of sensors in the two-component regulator family. This discovery
      shows that EPS I production by P. solanacearum is simultaneously controlled by
      dual two-component sensors.

PMID- 8152374
TI  - Trachoma and LGV biovars of Chlamydia trachomatis share the same
      glycosaminoglycan-dependent mechanism for infection of eukaryotic cells.
AB  - A sulphated glycosaminoglycan-dependent mechanism of microbial infection for
      mammalian cells was characterized for the Chlamydia trachomatis trachoma and
      lymphogranuloma venereum (LGV) biovars. We demonstrated that the trachoma and LGV
      biovars compete for the same receptor(s) on host cells and that their infectivity
      was inhibited by heparin or heparan sulphate. Using a specific heparan sulphate
      lyase (heparitinase) to treat organisms, the infectivity of both biovars was
      abolished. Furthermore, exogenous heparan sulphate rescued chlamydial infectivity
      following treatment with heparitinase and the restored infectivity was
      neutralized by an anti-heparan sulphate monoclonal antibody. These data suggest
      that heparan sulphate-like-mediated interactions between C. trachomatis and
      eukaryotic cells are essential for infectivity.

PMID- 8152375
TI  - Ordered cosmid library and high-resolution physical-genetic map of Helicobacter
      pylori strain NCTC11638.
AB  - Helicobacter pylori is a Gram-negative bacterium that infects the human gastric
      mucosa, causes gastritis and contributes to the development of peptic ulcers and
      gastric cancer. To facilitate molecular genetic analysis of this pathogen, we
      constructed a approximately 20-fold redundant cosmid library and physical/genetic
      map of strain NCTC11638. Genomic DNA fragments were cloned into the cosmid vector
      Lorist6, and clones were ordered by hybridization with several types of probes:
      (i) ends of cloned DNAs; (ii) chromosomal Notl digest fragments; (iii) cosmids
      containing Notl sites; and (iv) specific genes. Seven hundred and fifty-one
      cosmids were mapped to one of three contigs covering > 90% of the chromosome, and
      are represented by a 68-cosmid miniset. The order of cosmids was confirmed and
      extents of overlap among them were estimated by restriction analysis. All
      currently known H. pylori genes were mapped, including those for a cytotoxin
      (vacA), cytotoxin-associated protein (cagA), urease and regulatory functions
      (ureAb, ureD and ureH), catalase (katA), major and minor flagellins (flaA and
      flaB), heat-shock (stress) and chaperone proteins (dnaK, htA, hspB (groEL)),
      prokaryotic ferritin (pfr), an adhesin subunit (hpaA), a surface protein (26
      kDa), and 16S and 23S ribosomal RNAs (two genes each). The orientations of eight
      genes or clusters were determined, and two repetitive sequences were also found.
      The gene order and rRNA gene copy number determined here differed from that
      reported for an unrelated strain, which suggests considerable flexibility in H.
      pylori genome organization.

PMID- 8152376
TI  - Leucine-responsive regulatory protein, IS1 insertions, and the negative regulator
      FaeA control the expression of the fae (K88) operon in Escherichia coli.
AB  - Nucleotide sequence analysis of the fae operon encoding the biosynthesis of K88
      fimbriae revealed the presence of two divergently transcribed regulatory genes,
      faeA and faeB, separated by two inverted IS1 insertions. The amino acid sequences
      of the regulatory proteins FaeA and FaeB show similarity to the primary structure
      of corresponding regulatory proteins involved in the biosynthesis of Pap and S
      fimbriae. Expression of faeA is positively controlled by the FaeA protein,
      whereas K88 fimbriae production is negatively controlled by the co-operative
      activity of FaeA and the leucine-responsive regulatory protein (Lrp). Exchange of
      FaeA for Papl, a positive regulator of Pap fimbriae expression, also represses
      K88 production indicating that the combination Papl/Lrp has opposite effects on
      fae and pap expression. Mutations in faeB had no effect on the biosynthesis of
      K88 fimbriae. The presence of the two IS1 insertions is hypothesized to
      neutralize part of the repression of K88 biosynthesis by FaeA/Lrp. Like pap, the
      fae operon does not respond to exogenous leucine.

PMID- 8152377
TI  - Expression and role of the universal stress protein, UspA, of Escherichia coli
      during growth arrest.
AB  - The synthesis of the small, cytoplasmic protein UspA universal stress protein A)
      of Escherichia coli is induced as soon as the cell growth rate falls below the
      maximal growth rate supported by the medium, regardless of the condition
      inhibiting growth. The increase in UspA synthesis appears to be the result of
      induction of the monocistronic uspA gene. Induction of this gene during a heat
      shock treatment is demonstrated to be the result of transcriptional activation of
      a sigma 70-dependent promoter which has previously been shown to be activated
      also during carbon starvation-induced growth arrest. Mutant cells lacking UspA
      grow at rates indistinguishable from the isogenic parent at different
      temperatures and in the presence of different growth inhibitors but are impaired
      in their ability to survive prolonged periods of complete growth inhibition
      caused by a variety of diverse stresses, including CdCl2, H2O2, DNP, CCCP
      exposure, and osmotic shock. Moreover, the uspA mutation results in an increased
      sensitivity of cells to carbon-source starvation (i.e. glucose, glycerol or
      succinate depletion). Also, the mutation causes a marked alteration in the timing
      of starvation protein expression but protein expression during steady-state
      growth appears to be normal. The results presented have prompted us to postulate
      that UspA may have a general protective function related to the growth arrest
      state.

PMID- 8152378
TI  - Periplasmic disulphide bond formation is essential for cellulase secretion by the
      plant pathogen Erwinia chrysanthemi.
AB  - Secretion to the cell exterior of cellulase EGZ and of at least six pectinases
      enables the Gram-negative Erwinia chrysanthemi to cause severe plant disease. The
      C-terminal cellulose-binding domain (CBD) of EGZ was found to contain a
      disulphide bond which forms, in the periplasm, between residues Cys-325 and Cys
      382. Dithiothreitol (DTT)-treatment of native EGZ showed that the disulphide bond
      was dispensable, both for catalysis and cellulose binding. Adding DTT to E.
      chrysanthemi cultures led to immediate arrest of secretion of EGZ which
      accumulated in the periplasm where the CBD was eventually proteolysed. Site
      directed mutagenesis that affected Cys residues involved in disulphide bond
      formation resulted in molecules that were catalytically active and able to bind
      to cellulose but were no longer secreted. Instead they accumulated in the
      periplasm. Interestingly, the region around EGZ Cys-325 is conserved in two
      pectinases secreted by the same pathway as EGZ. We conclude that the conserved
      Cys, and possibly adjacent residues, bear essential information for EGZ to be
      secreted and that periplasmic disulphide bond formation is an obligatory step
      which provides a pre-folded functional form of EGZ with secretion competence.

PMID- 8152379
TI  - Genetic selection for mutations that impair the co-operative binding of lambda
      repressor.
AB  - Bacteriophage lambda repressor binds co-operatively to adjacent pairs of DNA
      target sites. A novel combination of positive genetic selections, involving two
      different operon fusions derived from P22 challenge phages, was used to isolate
      mutant lambda repressors that have lost the ability to bind co-operatively to
      tandem sites yet retain the ability to bind a strong, single site. These cb (co
      operative binding) mutations result in 10 different amino acid changes, which
      define eight residues in the carboxyl-terminus of repressor. Because challenge
      phage derivatives may be applied to study essentially any specific protein-DNA
      interaction, analogous combinations of genetic selections may be used to explore
      the ways that a variety of proteins interact to assemble regulatory complexes.

PMID- 8152380
TI  - An inner-membrane-associated virulence protein essential for T-DNA transfer from
      Agrobacterium tumefaciens to plants exhibits ATPase activity and similarities to
      conjugative transfer genes.
AB  - The 9.5 kb virB operon is the largest of the six major operons in the Ti plasmid
      vir region. This operon contains eleven genes, the largest of which is virB4.
      This gene encodes an 84 kDa protein whose function has not been identified. Its
      roles in conferring virulence on Agrobacterium tumefaciens and in the T-DNA
      transfer process were determined by generating non-polar mutants by using the
      Tn5pvirB transposon in which the virB promoter is transcribed downstream of its
      position of insertion. Several independent mutants were isolated and each
      insertion site in virB4 was confirmed by nucleotide sequence analysis. These
      mutants were tested for T-DNA transfer ability by agroinfection and for
      tumorigenicity by inoculation in Brassica and Datura. All mutants were
      agroinfection- and tumorigenicity-negative. These data strongly suggest that
      virB4 is essential for both the interkingdom transfer of the T-DNA and virulence.
      Furthermore, by using anti-VirB4 serum, the protein product of virB4 was
      localized to the inner-membrane fraction of A. tumefaciens. Purified VirB4
      protein hydrolyses ATP and this activity was quenched by the anti-VirB4 serum.
      The energy generated by VirB4 ATPase therefore may be used to transfer T-DNA or
      to assemble the T-DNA transfer apparatus on the bacterial membrane. Protein
      sequence analyses revealed striking similarities between VirB4 protein and the
      proteins required for conjugative transfer, which include TraC, TrwK, and TrbE of
      plasmids F, R388, and RP4, respectively. These findings suggest that VirB
      proteins play a direct role in the assembly of a conjugative transfer apparatus
      required for the transfer of the T-DNA from A. tumefaciens to plant cells.

PMID- 8152381
TI  - International perspective of vocational options for people with mental
      retardation: the promise and the reality.
AB  - Developments in research into the vocational needs and preparation of people with
      mental retardation were briefly traced over recent decades. The premise was made
      that the study of vocational programs for this population should be examined in
      the context of the labor market developments of individual countries. Areas for
      future research were identified, with specific reference to community-based
      vocational programs.

PMID- 8152382
TI  - Comparison of personal and computer-assisted instruction for children with
      autism.
AB  - The potential of computer-assisted instruction in working with individuals who
      have autism has been a controversial topic for both teachers and parents since
      its introduction 2 decades ago. In the present study computer-assisted
      instruction was compared with personal instruction. Four children with autism
      participated. Although 3 of them showed better motivation and fewer behavior
      problems in computer-assisted instruction compared to personal instruction, this
      did not affect their learning-rate. Future directions of computer-assisted
      instruction research for individuals with autism were discussed.

PMID- 8152383
TI  - Sex education programs for people with mental retardation.
AB  - Data relating to sexual knowledge, needs, and experience of people with mental
      retardation and attitudes of caregivers and parents were evaluated. Results
      suggest that individuals with mental retardation have an unmet need for sexual
      knowledge, which has occurred, in part, because of the largely negative attitudes
      of caregivers and parents about the sexuality of these individuals. Their
      sexuality is either ignored or perceived as a problem. Available sex education
      programs are generally concerned with providing information on a limited range of
      subjects, with no assessments of individuals' needs or of reliability, validity,
      or effectiveness of programs. Adequate sex education must be provided to protect
      the rights of this population.

PMID- 8152384
TI  - Organizational predictors of staff stress, satisfaction, and intended turnover in
      a service for people with multiple disabilities.
AB  - Questionnaire data were collected from 64 direct-care staff members in a
      residential facility for people with multiple disabilities. Path analyses
      identified a number of organizational factors that predicted levels of perceived
      stress, overall job satisfaction, overall life satisfaction, and perceived
      likelihood of leaving the organization. Factors found to be common influences on
      all outcome measures included support from other staff (largely supervisory), job
      variety, staff perceptions of organizational democracy, goodness-of-fit between
      the attitudes and aims of staff and those of the organization, staff development,
      and income. Implications of the findings for service managers were discussed.

PMID- 8152385
TI  - Leisure-related peer preference choices of individuals with Down syndrome.
AB  - Although full participation in community life should be available to all
      individuals with mental retardation, some may prefer segregated participation in
      selected activities. Freedom of choice is particularly important in leisure
      activities. In this exploratory study we investigated whether individuals with
      Down syndrome would prefer to participate in bowling with other people who had
      Down syndrome or with people who had no apparent mental retardation. Structured
      interviews, in conjunction with videotapes of two bowling groups, revealed that
      15 of the 21 adult subjects preferred to bowl with others who had Down syndrome.
      If either segregated or integrated activities are denied to adults with mental
      retardation, their opportunities for experiencing the benefits of freely chosen
      leisure participation are also systematically denied.

PMID- 8152386
TI  - Constraints on the participation of individuals with mental retardation in
      mainstream recreation.
AB  - A questionnaire was designed to investigate the influence of skill level,
      behavioral characteristics, and labeling upon attitudes toward the participation
      of individuals with mental retardation in a recreation activity. The respondents
      were 320 members of 12 private tennis clubs. High multiple correlations between
      the predictor variables, attitude toward the behavior, and subjective norm, with
      behavioral intention supported the model of the theory of reasoned action.
      Attitudes, subjective norms, and behavioral intentions toward individuals with
      mental retardation were favorable regardless of the label assigned and perceived
      skill level. Perceived behavior of the target person, rather than skill level and
      label, was the more salient influence upon attitudes, subjective norms, and
      behavioral intentions.

PMID- 8152387
TI  - Socioeconomic status and the prevalence of mental retardation in Bangladesh.
AB  - Results of a population-based study of the prevalence of mental retardation among
      2- to 9-year-old children in Bangladesh were reported. More than 10,000 children
      were screened for mental retardation and other disabilities. All children with
      positive screening results plus a random sample with negative results were
      referred for clinical evaluations. The prevalence rates per 1,000 of severe and
      mild mental retardation in this population were 5.9 and 14.4, respectively. As
      found in studies in developed countries, the prevalence of mild mental
      retardation was strongly and significantly associated with low socioeconomic
      status, whereas the association for severe mental retardation was relatively weak
      and not significant.

PMID- 8152388
TI  - Social interactions in the neighborhood: cultural approach to social integration
      of individuals with mental retardation.
AB  - Research conducted in Treguier (Brittany) on community integration of individuals
      with mental retardation was reported. Change in social status as reflected in
      social interactions in a community was examined. Douglas' (1978) grid-group
      typology of cultural regimens was employed to measure this status. Each regime
      links the presence of individuals with mental retardation to the construction of
      a community of shared values and produces different responses of integration.

PMID- 8152389
TI  - Summary of national survey of older people with mental retardation in New
      Zealand.
AB  - The present paper is a summary of a national project to investigate prevalence,
      health status, and service needs of people with mental retardation born before
      1940. In 1990, 42% of this population resided in institutions, 7% with family,
      13% in nursing homes, and 38% in community-based residential facilities. Of 1,063
      identified, 135 had Down syndrome, 25% had psychiatric diagnosis, 17% had
      epilepsy, and 23% had no major disability. About 32% had visual problems, 40% had
      weight problems, and 75% received regular medication. Of this population, 75% had
      at least occasional contact with their families. Major needs identified were
      medical care, community, and recreational services.

PMID- 8152390
TI  - Compensation and turnover of direct-care staff in developmental disabilities
      residential facilities in the United States. I: Wages and benefits.
AB  - This study was based on a representative national sample of more than 1,600
      residential facilities serving individuals with developmental disabilities in all
      50 states and the District of Columbia. The mean starting wage for direct-care
      workers in publicly operated institutions in FY 1990 was approximately 31% more
      than the wage for similar workers in privately operated facilities. The mean
      starting wage in private facilities was only about 3% above the poverty level for
      a family of three. Wages, in real economic terms, have declined significantly
      during the last decade. The wage differential between public and private
      facilities has doubled during the past 10 years. Implications of these findings
      for the field and for future research were discussed.

PMID- 8152391
TI  - A simple method for classification of antibiotics using ion exchange resins added
      to agar plates.
AB  - Using two different ion-exchange resins (Dowex 50W-X4 as cation and Dowex 1-X4 as
      anion) added directly to assay plates seeded with Bacillus subtilis or
      Micrococcus luteus, the size of the inhibitory zone produced by 36 antimicrobial
      agents around a disc or cup was characterized into various types, such as acidic,
      basic or amphoteric. An increase of the inhibition zone following addition of 15%
      Dowex 50W-X4 was evident in penicillins except for ampicillin and penicillin-G,
      and polyethers. Aminoglycosides, macrolides and colistin, lincomycin, and
      sulphonamides on assay medium treated with Dowex 1-X4 showed a similar effect on
      the inhibition zone. Tetracyclines, virginiamycin, oxolinic acid and furazoridone
      revealed no effects on the inhibition zone with either of the resins. These
      antibiotics could be divided into various groups on the basis of their chemical
      structure. This simple and rapid method may be useful for routine laboratory
      testing of residual antibiotics in meat.

PMID- 8152392
TI  - Antagonism between bactericidal activities of 4-quinolones and coumarins gives
      insight into 4-quinolone killing mechanisms.
AB  - At concentrations exceeding their MICs, novobiocin and coumermycin antagonised
      the bactericidal activities of nalidixic acid, ciprofloxacin, ofloxacin and
      norfloxacin against Escherichia coli KL16. The sensitivities to killing by
      ciprofloxacin of four mutant derivatives of KL16 carrying gyrA, nalB, nal24 or
      nal31 alleles were also antagonised by novobiocin. The activities of drug
      combinations were tested in nutrient broth, which allowed expression of 4
      quinolone killing mechanisms A, B and C. They were also tested in nutrient broth
      plus rifampicin to inhibit mechanisms A and C of the 4-quinolones, and in
      phosphate-buffered saline, which inhibited mechanism A. Results showed that
      novobiocin antagonised mechanism C, but not B, of both ciprofloxacin and
      ofloxacin, but did not antagonise mechanism C of norfloxacin. A review of these
      and other data indicates that mechanism B may result from the activities of SOS
      error-prone DNA repair on an irreversibly-bound drug-gyrase-DNA complex, and that
      mechanism C is mediated via drug interaction with the B subunit of DNA gyrase.

PMID- 8152393
TI  - Effects of hormones on chemotaxis in Tetrahymena: investigations on receptor
      memory.
AB  - The peptide type hormones such as insulin and adenocorticotropic hormone (ACTH)
      have a positive chemoattractant effect on Tetrahymena. Non-hormone protein
      sulphate provoked negative chemoattraction. Of the amino acid type hormones,
      serotonin produced negative, and the histamine and di-iodotyrosine induced
      positive chemotactic effects. The first encounter with these molecules may modify
      the chemotactic behaviour of the progeny cells. In a significant number of cases
      there was a different response after repeated encounters of cells and hormones.

PMID- 8152394
TI  - Lack of correlation between the presence of 70 kb plasmid and plasmid-associated
      determinants of Yersinia enterocolitica.
AB  - The relatedness between the plasmids from Yersinia enterocolitica 0:4.32 and 0.9
      was examined. Plasmid 0:4.32 was found in many clinical isolates of Y.
      enterocolitica and was related to pYV plasmid of Y. enterocolitica 0:9. The
      homology between the plasmid and chromosomal DNAs of strains 0:4.32 and 0:9 was
      examined. The Ca(2+)-dependent expression of the OmpF and OmpC proteins is
      described.

PMID- 8152395
TI  - Rochalimaea henselae organisms possess an elevated capacity of binding to
      peripheral blood lymphocytes from patients with cat scratch disease.
AB  - Cat scratch disease (CSD) is a clinical condition whose aetiological agent,
      according to recent findings, is of bacterial origin. Two Gram-negative bacteria
      are invoked as causative agents of CSD, namely Afipia felis and Rochalimaea
      henselae. In this paper, five patients with suspected CSD were studied in terms
      of binding capacity of A. felis and R. henselae to their own peripheral blood
      lymphocytes (PBL). This parameter was correlated with serum antibody titres to
      both A. felis and R. henselae, as determined by an indirect fluorescence assay
      (IFA). Results demonstrate that in four out of five cases binding of R. henselae
      to PBL was higher than that observed with A. felis. In two cases serum antibody
      titres to both bacteria were lower or absent, while in the other two patients
      serum antibody titres to R. henselae were significantly high. In one case only,
      characterized by elevated titres of serum antibodies to A. felis, values of
      cytoadherence exhibited by this bacterium were similar to those observed with R.
      henselae. The results suggest that bacterial binding to lymphocytes may represent
      an additional parameter to support diagnosis of CSD.

PMID- 8152396
TI  - Treatment of relapsing acute lymphoblastic leukemia in childhood. III.
      Experiences with 54 first bone marrow, nine isolated testicular, and eight
      isolated central nervous system relapses observed 1985-1989.
AB  - Of 54 children with acute lymphoblastic leukemia (ALL) and first hematological
      recurrence observed between 1985 and 1989, 31 relapsed while still on treatment
      and 23 after cessation of therapy. Of the former, only one survived. Of the
      latter, 11 children survived after a minimum follow-up of 25 months. During the
      same period, a first isolated testicular relapse was observed in nine boys, of
      whom six survived, and an isolated CNS relapse in eight patients, of whom three
      survived. As a rule, survivors of a bone marrow or testicular relapse were doing
      well while those surviving a CNS relapse had considerable neuropsychological
      sequelae. These results, compared with those of two preceding studies, suggest
      that with intensification of front-line treatments, it becomes more difficult to
      rescue children who relapse, particularly those with a bone marrow relapse while
      on therapy.

PMID- 8152397
TI  - Mitoxantrone, 5-FU, and leucovorin in breast cancer.
AB  - Eighteen patients (17 evaluable for response) with metastatic breast cancer were
      treated with mitoxantrone 10 mg/m2 day 1, followed by 5-fluorouracil 375 mg/m2
      day 1-5, and high-dose leucovorin 500 mg/m2 day 1-5 given every 28 days. There
      was one complete and four partial responses for an objective response rate of 30%
      and 41% stable disease. The major toxicities were hematologic and
      gastrointestinal. This regimen has activity in metastatic breast cancer
      comparable to conventional and/or standard chemotherapy regimens for advanced
      disease.

PMID- 8152398
TI  - Cerebral irradiation causes blunted pubertal growth in girls treated for acute
      leukemia.
AB  - The improved treatment of childhood leukemia is a major achievement. The late
      effects of the treatment need further investigation. Growth inhibition has been
      demonstrated in earlier studies. Growth and the timing of puberty were studied in
      179 girls who had been treated for acute lymphoblastic leukemia (ALL) in Denmark,
      Finland, Norway, and Sweden. The patients were divided into two groups according
      to mode of CNS prophylaxis: with or without cerebral irradiation. Longitudinal
      analysis of 103 patients showed no difference in prepubertal growth in irradiated
      and nonirradiated girls. Growth during puberty was normal in girls without
      irradiation and below normal in irradiated girls. There was no difference in
      growth between girls after 24 Gy or 20 Gy of cerebral irradiation. Irradiated
      girls had a final height which was one SD less than expected before puberty and
      menarche occurred one year earlier than in the nonirradiated girls. Prophylactic
      cerebral irradiation is the most important factor for subnormal growth after
      treatment for ALL. There is no short-term influence on growth but the effects of
      irradiation become apparent several years after therapy when girls enter puberty
      somewhat early and have a subnormal pubertal growth. Growth and growth hormone
      (GH) levels should be evaluated several years after CNS irradiation, and
      treatment with GH and/or luteinizing hormone releasing hormone (LHRH) analogues
      may be considered.

PMID- 8152399
TI  - Multicentric angiofollicular lymph node hyperplasia and associated carcinoma.
AB  - There is a well described association between multicentric angiofollicular
      hyperplasia and non-Hodgkin's lymphoma and/or Kaposi's sarcoma. Two cases of
      multifocal angiofollicular hyperplasia and associated carcinomas and non
      Hodgkin's lymphoma are reported. We suggest that underlying immunological defects
      in patients with multicentric angiofollicular hyperplasia make them susceptible
      to the development of carcinomas, as well as non-Hodgkin's lymphoma and Kaposi's
      sarcoma.

PMID- 8152400
TI  - Hypertensive crises induced by treatment of malignant pheochromocytoma with a
      combination of cyclophosphamide, vincristine, and dacarbazine.
AB  - Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine
      (CVD) is an effective treatment regimen for malignant pheochromocytoma. There
      have not been any significant acute cardiovascular effects reported following CVD
      treatment. Among seven patients with malignant pheochromocytoma treated with CVD
      at our institution, two patients with labile hypertension developed hypertensive
      crisis following CVD treatment. The marked increase in blood pressure correlated
      with an increase in urinary excretion of catecholamine metabolites in one
      patient. Further hypertensive crises following subsequent CVD treatments were
      avoided by optimizing each patient's antiadrenergic therapy. Similar to the
      approach used preoperatively for patients with resectable pheochromocytoma,
      maximal antiadrenergic therapy is essential in preventing hypertensive crises in
      patients with malignant pheochromocytoma undergoing CVD treatment.

PMID- 8152401
TI  - Hyperthermic isolated limb perfusion with cis-diamminedichloro-platinum. II. An
      experimental study in dogs with a balloon-occlusion technique for repeated high
      dose treatment.
AB  - Isolated organ perfusion is attractive for regional high-dose chemotherapy
      because of its advantage to reduce whole body toxicity. Intraoperative
      hyperthermic isolated perfusion procedures involving a heart-lung machine have
      been developed, but repeated treatments carry a high risk of vessel and tissue
      damage. Therefore, a study of isolated hyperthermic limb perfusion in four dogs
      was conducted using a balloon-occlusion technique including a hyperthermia unit,
      two low-flow rotary pumps, a bubble oxygenator, and two polyurethane balloon
      catheters. After 15 min infusion of cisplatinum the concentrations of serum
      platinum (Pt) in the isolated limb and in the whole body were measured by atomic
      absorption spectroscopy. Regional exposure to Pt was more than 10-fold higher
      than systemic exposure. After 60 min isolated limb perfusion, the area under the
      curve (AUC) of Pt concentrations in the isolated limb showed values between 767.4
      and 1055.6 micrograms/l x 60 min, whereas in the whole body values between 59.8
      and 75.9 micrograms/l x 60 min were obtained. Repeated isolated limb perfusions
      with the balloon-occlusion technique were performed in three dogs without
      systemic side effects. This model of regional chemotherapy may be useful for
      preoperative chemotherapy in malignant tumors of the limbs.

PMID- 8152402
TI  - Karyotype evolution in a patient with Down syndrome and acute leukemia following
      a congenital leukemoid reaction.
AB  - We report the serial cytogenetic study of a patient with Down syndrome who
      experienced a congenital leukemoid reaction, underwent a spontaneous remission
      within four months, and subsequently developed acute myeloid leukemia at 16
      months. A blood chromosome study to rule out Down syndrome performed at age 24
      days, during the leukemoid reaction, revealed a 47,XX,+21 karyotype. The
      diagnosis of acute leukemia was made at 16 months, at which time a chromosome
      study, on bone marrow, was performed. This analysis revealed a clonal karyotype
      of 47,XX,+21,-22,+der(22)t(1;22)(q21;q13) in all but one cell studied. The single
      apparently nonclonal cell showed a karyotype of 49,XX,+12,-13,
      19,+der(19)t(19;?)(q11;?)x2,+21,+22. A third chromosome study at 19 months
      indicated the original leukemic clone with t(1;22) (q21;q13) had been replaced by
      the clone represented by the single cell with 49 chromosomes seen in the previous
      chromosome study. This case of an infant with Down syndrome and acute leukemia
      illustrated rapid evolution and a transitory nature to clonal chromosome
      aberrations while retaining AML morphology and course.

PMID- 8152403
TI  - Kaposi's sarcoma of the bone marrow presenting with fever of unknown origin.
AB  - Kaposi's sarcoma (KS) has become more common in the United States with the spread
      of the Acquired Immunodeficiency Syndrome (AIDS) epidemic. The epidemic form
      associated with AIDS involves primarily skin and visceral organs. Bone marrow
      involvement is rare. We present a case of Kaposi's sarcoma that was diagnosed
      upon bone marrow biopsy, without skin or visceral involvement, that presented
      with fever of unknown origin which responded to indomethacin and anti-KS
      chemotherapy. Kaposi's sarcoma of the bone marrow should be considered in the
      differential of febrile illness of unknown origin in patients with AIDS.

PMID- 8152404
TI  - Successful treatment of acute lymphoblastic leukemia in a child with cystic
      fibrosis.
AB  - A 3 1/2 year old girl with cystic fibrosis who underwent successful treatment for
      acute lymphoblastic leukemia remains in complete remission 36 months after
      diagnosis. We also report high clearance rates of three antineoplastic agents in
      this patient. Drug doses were adjusted to achieve optimal systemic exposure.

PMID- 8152405
TI  - Peritoneal metastases in two patients with pineoblastoma and ventriculo
      peritoneal shunts.
AB  - We report the uncommon occurrence of ventriculo-peritoneal shunt-associated
      peritoneal metastases in two patients with pineoblastoma. In one patient, the
      peritoneal cavity was the only site of recurrence; there was no evidence of
      disease recurrence in the central nervous system. One other patient with
      recurrent intracranial disease had synchronous, but asymptomatic, peritoneal
      metastases which were detected on an elective ultrasound. Although rare,
      peritoneal metastases appear to respond well to systemic chemotherapy. Ultrasound
      surveillance of the abdomen should be considered as a part of the routine follow
      up evaluation in patients with embryonal central nervous system tumors and
      ventriculo-peritoneal shunts.

PMID- 8152406
TI  - Childhood Liver Tumour Tissue Storage Programme: a SIOP liver tumour study
      initiative.

PMID- 8152407
TI  - "Multifocal synchronous osteosarcoma: the Scottish Bone Tumour Registry
      experience" by Jones et al., 1993.

PMID- 8152408
TI  - Theophylline misadventures: Part II.
AB  - Except for overdose ingestions, excessive theophylline serum concentrations can
      be attributed predominantly to therapeutic misadventure. Utilizing medico-legal
      case reports as a core, this article considers how theophylline toxicity is
      manifested in several major organ systems and discusses drug/disease interactions
      with theophylline that may alter serum theophylline concentrations, necessitating
      dose adjustments. Theophylline overdose is associated with significant morbidity
      and mortality risks. Overdose treatment, based on use of serum concentrations, is
      addressed. An understanding of all these factors can help caregivers avoid
      theophylline morbidity and mortality in neonatal patients.

PMID- 8152409
TI  - Vancomycin dosing in neonatal patients: the controversy continues.
AB  - During the past decade, an increasing incidence of staphylococcus organisms
      resistant to penicillinase-resistant penicillins has necessitated the use of
      vancomycin. This increased utilization has revitalized research concerning
      efficacious vancomycin dosing regimens for premature neonates, infants, and
      children. Vancomycin dosing in neonates is variable because this patient
      population has decreased renal clearance and a larger volume of distribution than
      infants, children, or adults. The observation of the variability in vancomycin
      clearance and volume of distribution in infants with the same postconceptional
      age (PCA) but different gestational age (GA) suggests that the rates of
      maturation both extrauterine and intrauterine for disposition mechanisms of
      vancomycin are similar when PCAs are equal. Conditions such as patent ductus
      arteriosus, respiratory distress syndrome, sepsis, and asphyxia may further
      complicate the renal maturation process. Few investigations suggest vancomycin
      dosing regimens. Most of these studies propose dosing regimens based on
      retrospective analysis of vancomycin pharmacokinetics obtained from regimens
      based on physician discretion. To ensure efficacious and rational vancomycin
      dosing for premature neonates and infants, regimens should consider PCA as well
      as body weight.

PMID- 8152410
TI  - Selecting antibiotics for nosocomial bacterial infections in patients requiring
      neonatal intensive care.
AB  - Nosocomial infections increase neonates' morbidity, hospital costs, and
      mortality. These infections occur most commonly in very low birth weight infants,
      who frequently required plastic intravascular catheters and parenteral nutrition.
      Diagnosis often relies on a combination of laboratory tests and nonspecific
      clinical signs. Criteria for diagnosing nosocomial infections have been published
      by the Centers for Disease Control (CDC) and should be used to standardize the
      identification of cases. Initial antibiotic therapy depends on (1) the bacterial
      species most likely to cause infection, (2) antibiotic resistance patterns in
      one's own hospital, (3) the patient's clinical condition, and (4) previous
      antibiotic therapy. Antibiotic coverage of both gram-positive and gram-negative
      bacteria is necessary. Following laboratory identification of the infecting
      organism and the antibiotic susceptibility results, the patient should be
      reevaluated and definitive therapy prescribed. Multiple antibiotics may be needed
      as definitive therapy if (1) the infecting organism is likely to develop
      resistant mutants during therapy (e.g., Pseudomonas species), (2) higher
      bactericidal serum activity is required than can usually be achieved with a
      single agent (e.g., enterococci, Listeria), (3) the patient is neutropenic or
      otherwise severely immunocompromised, or (4) blood cultures are persistently
      positive for bacteria despite appropriate therapy with a single agent. Attempts
      to prevent nosocomial bacteremias by routinely administering prophylactic
      vancomycin may hasten the development of vancomycin-resistant, coagulase-negative
      staphylococci or enterococci and should be avoided.

PMID- 8152411
TI  - Current strategies in the management of bronchopulmonary dysplasia: the role of
      corticosteroids.
AB  - Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease of
      multifactorial etiology that develops in some premature neonates who survive
      hyaline membrane disease (HMD). The role of corticosteroids as a cause of ongoing
      secondary damage in BPD remains speculative, but strategies to control this
      reactive inflammation form the basis for the use of corticosteroids. In several
      controlled clinical trials conducted to assess the role of corticosteroids in
      BPD, dexamethasone has been administered at a dose of 0.5 mg/kg/day, followed by
      a tapering regimen. Consistent benefits of corticosteroid use have been a
      decrease in the number of ventilator days and a facilitation of extubation.
      Common, often transient, side effects include hypertension, hyperglycemia, and
      poor weight gain. More serious side effects include myocardial hypertrophy,
      suppression of the hypothalamic-pituitary-adrenal (HPA) axis, perforated gastric
      ulcers, and gastrointestinal hemorrhage. The long-term effects on growth and
      development are unknown. The role of corticosteroids in the management of BPD
      still remains controversial. The dosage, timing, duration of therapy, and length
      of tapering period for dexamethasone treatment remain unresolved issues. The
      current literature supports the judicious use of corticosteroids to decrease the
      number of days on the ventilator and to facilitate extubation in selected infants
      with BPD. Further controlled clinical trials are necessary before the routine use
      of corticosteroids in the management of BPD can be recommended.

PMID- 8152412
TI  - The national pain management guideline: implications for neonatal intensive care.
      Agency for Health Care Policy and Research.
AB  - A wide range of acute pain management strategies is used in various patient
      populations throughout the United States. A guideline, developed by an
      interdisciplinary panel convened by the Agency for Health Care Policy and
      Research, offers health care providers a "coherent yet flexible approach to pain
      assessment and management for use in daily practice." The goal of the guideline
      and application to daily practice in the NICU are described.

PMID- 8152413
TI  - Genetic interactions among genes involved in the STT4-PKC1 pathway of
      Saccharomyces cerevisiae.
AB  - Loss of yeast protein kinase C function results in three distinct phenotypes:
      staurosporine sensitivity, cell lysis and blockage of cell cycle progression at
      the G2/M boundary. Genetic analysis of the PKC1/STT1 protein kinase C gene and
      its interactions with STT4, encoding an upstream phosphatidylinositol 4-kinase,
      and BCK1, encoding a downstream protein kinase, reveal that they form part of a
      single pathway. However, the BCK1-20 mutation (a gain-of-function mutation of
      BCK1) or overexpression of PKC1 cannot suppress all of the phenotypes caused by
      the loss of STT4 function, strongly suggesting the existence of a branch point
      between STT4 and PKC1. We also describe the MSS4 gene, a multicopy suppressor of
      the temperature-sensitive stt4-1 mutation. MSS4 is predicted to encode a
      hydrophilic protein of 779 amino acid residues and is essential for cell growth.
      Based on genetic and biochemical data, we suggest that MSS4 acts downstream of
      STT4, but in a pathway that does not involve PKC1.

PMID- 8152414
TI  - The hypo-osmolarity-sensitive phenotype of the Saccharomyces cerevisiae hpo2
      mutant is due to a mutation in PKC1, which regulates expression of beta
      glucanase.
AB  - To obtain more information about the cell wall organization of Saccharomyces
      cerevisiae, we have developed a novel screening system to obtain cell wall
      defective mutants, using a density gradient centrifugation method. Nine hypo
      osmolarity-sensitive mutants were classified into two complementation groups,
      hpo1 and hpo2. Phase contrast microscopic observation showed that mutant cells
      bearing lesions at either locus became abnormally large. A gene that complemented
      the mutant phenotype of hpo2 was cloned and sequenced. This gene turned out to be
      identical to PKC1, which encodes the yeast homologue of mammalian protein kinase
      C. Complementation tests with pkc1 delta showed that hpo2 is allelic to pkc1. To
      study the reason for the fragility of hpo2 cells, cell wall was isolated and the
      glucan was analyzed. The amount of alkali, acid-insoluble glucan, which is
      responsible for the rigidity of the cell wall, was reduced to about 30% that of
      the wild-type cell and this may be the major cause of the fragility of the hpo2
      mutant cell. Analysis of total wall proteins in hpo2 mutant cells on SDS
      polyacrylamide gels revealed that a 33 kDa protein was overproduced two- to
      threefold relative to the wild-type level. This 33 kDa protein was identified as
      a beta-glucanase, encoded by BGL2. Disruption of BGL2 in the hpo2 mutant
      partially rescued the growth rate defect. This suggests that the PKC1 kinase
      cascade regulates BGL2 expression negatively and overproduction of the beta
      glucanase is partially responsible for the growth defect.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8152415
TI  - Characterization of the chromatin structure in the upstream region of the chicken
      alpha-globin gene domain.
AB  - The distribution of DNase I hypersensitive sites upstream of the chicken alpha
      globin gene cluster was studied. A group of hypersensitive sites with a complex
      pattern of tissue specificity, including erythroid-specific elements, was found
      at a distance of 11.5-14.5 kb upstream of the pi gene, the first gene in the
      cluster. The observations indicate that this area, located upstream of the block
      of AT-rich sequences and MAR sites (at -8 kb) and upstream of the site of
      permanent DNA attachment to the nuclear matrix (-3 kb), still belongs to the
      domain of the alpha-globin genes.

PMID- 8152416
TI  - Functional expression of the yeast FLP/FRT site-specific recombination system in
      Nicotiana tabacum.
AB  - The FLP/FRT site-specific recombination system of Saccharomyces cerevisiae was
      expressed in stably transformed tobacco plants. The FLP protein efficiently
      catalyzes recombination between two directly repeated FLP recombination target
      (FRT) sites, deleting the sequence between them. In the constructs tested here,
      this deletion places the CaMV 35S promoter adjacent to a hygromycin resistance
      marker; transcriptional activation of the marker allows direct selection of
      recombination events. After crossing plants containing an integrated FLP
      expression construct with plants containing a FLP substrate, F1 seedlings can be
      selected directly for hygromycin resistance, indicating that recombination occurs
      at, or very early after zygote formation. Molecular analysis confirmed the
      expected recombination product.

PMID- 8152417
TI  - Alpha-domain of human metallothionein IA can bind to metals in transgenic tobacco
      plants.
AB  - With a view to exploring its use as a metal-binding factor in transgenic plants
      we prepared the alpha-domain of metallothionein by reconstitution of rabbit
      apometallothionein and proteolysis of MT-1 and MT-2 with subtilisin. The isolated
      alpha-domains were characterised by UV and CD spectroscopy Double-Stranded. DNA
      encoding the alpha-domain (106 bp) of the human MT-IA was constructed from
      chemically synthesized oligomers by repair synthesis and enzymatic ligation,
      cloned into pUC19 and sequenced. A expression construct containing the cloned
      alpha-domain was introduced into tobacco cells on a disarmed Agrobacterium
      tumefaciens Ti-plasmid. Transformed tobacco cells were selected and regenerated
      on medium containing cadmium and kanamycin. The growth of roots and shoots of
      transformants was unaffected by up to 100 microM cadmium, whereas control plants
      showed severe inhibition of root and shoot growth, and chlorosis of leaves on
      medium containing only 10 microM cadmium. Southern hybridization confirmed the
      presence of the transgene in the transformed plant tissues. The concentration of
      human alpha-domain peptides in transgenic tobacco leaves was determined by the
      Cd/hemoglobin saturation assay and polarography using the rabbit alpha-domain as
      standard. The results indicate that the alpha-domain, one of two domains in MT
      molecules, is not only stable in vitro, but is also expressed efficiently and
      functions independently in transgenic plant cells.

PMID- 8152418
TI  - Mutations conferring lincomycin, spectinomycin, and streptomycin resistance in
      Solanum nigrum are located in three different chloroplast genes.
AB  - A number of Solanum nigrum mutants resistant to the antibiotics spectinomycin,
      streptomycin and lincomycin have been isolated from regenerating leaf strips
      after mutagenesis with nitroso-methylurea. Selection of streptomycin- and
      spectinomycin-resistant mutants has been described earlier. Lincomycin-resistant
      mutants show resistance to higher levels of the antibiotic than used in the
      initial selection, and in the most resistant mutant (L17A1) maternal inheritance
      of the trait was demonstrated. The lincomycin-resistant mutant L17A1 and a
      streptomycin plus spectinomycin resistant double mutant (StSp1) were chosen for
      detailed molecular characterisation. Regions of the plastid DNA, within the genes
      encoding 16S and 23S rRNA and rps12 (3') were sequenced. For spectinomycin and
      lincomycin resistance, base changes identical to those in similar Nicotiana
      mutants were identified. Streptomycin resistance is associated with an A-->C
      change at codon 87 of rps12 (converting a lysine into a glutamine), three codons
      upstream from a mutation earlier reported for Nicotiana. This site has not
      previously been implicated in streptomycin resistance mutations of higher plants,
      but has been found in Escherichia coli. The value of these mutants for studies on
      plastid genetics is discussed.

PMID- 8152419
TI  - Homologs of the yeast neck filament associated genes: isolation and sequence
      analysis of Candida albicans CDC3 and CDC10.
AB  - Morphogenesis in the yeast Saccharomyces cerevisiae consists primarily of bud
      formation. Certain cell division cycle (CDC) genes, CDC3, CDC10, CDC11, CDC12,
      are known to be involved in events critical to the pattern of bud growth and the
      completion of cytokinesis. Their products are associated with the formation of a
      ring of neck filaments that forms at the region of the mother cell-bud junction
      during mitosis. Morphogenesis in Candida albicans, a major fungal pathogen of
      humans, consists of both budding and the formation of hyphae. The latter is
      thought to be related to the pathogenesis and invasiveness of C. albicans. We
      have isolated and characterized C. albicans homologs of the S. cerevisiae CDC3
      and CDC10 genes. Both C. albicans genes are capable of complementing defects in
      the respective S. cerevisiae genes. RNA analysis of one of the genes suggests
      that it is a regulated gene, with higher overall expression levels during the
      hyphal phase than in the yeast phase. Not surprisingly, DNA sequence analysis
      reveals that the proteins share extensive homology at the amino acid level with
      their respective S. cerevisiae counterparts. Related genes are also found in
      other species of Candida and, more importantly, in filamentous fungi such as
      Aspergillus nidulans and Neurospora crassa. A database search revealed
      significant sequence similarity with two peptides, one from Drosophila and one
      from mouse, suggesting strong evolutionary conservation of function.

PMID- 8152420
TI  - Functional analysis of the zinc cluster domain of the CYP1 (HAP1) complex
      regulator in heme-sufficient and heme-deficient yeast cells.
AB  - CYP1 determines the expression of several genes whose transcription is heme
      dependent in yeast. It exerts regulatory functions even in the absence of heme,
      usually considered to be its effector. It mediates both positive and negative
      effects, depending on the target gene and on the redox state of the cell. In the
      presence of heme, it binds through a cysteine-rich domain in which a histidine
      residue occupies the position of the sixth and essential cysteine of the
      otherwise classical zinc cluster DNA-binding domain exemplified by GAL4. We
      constructed specific missense mutations in the potential CYP1 zinc cluster domain
      by site-directed mutagenesis and looked for regulatory effects of the mutated
      proteins under specific physiological conditions. We show that CYP1 does belong
      to the zinc cluster regulatory family since a sixth essential cysteine residue is
      indeed present, albeit at a modified position when compared to the consensus
      sequence. We also show that the amino acid preceding the first cysteine residue
      of the DNA-binding domain critically affects the efficiency of regulation both in
      the presence and in the absence of heme: mutations known to affect DNA binding
      under heme-sufficient conditions also affect regulation under heme-deficient
      conditions. We therefore surmise that regulation under heme-deficient conditions
      is dependent upon DNA binding.

PMID- 8152421
TI  - Characterization of the Saccharomyces cerevisiae nuclear gene CYB3 encoding a
      cytochrome b polypeptide of respiratory complex II.
AB  - Computer-assisted structural analysis of the predicted product of the previously
      described open reading frame (ORF) YKL4 located on the left arm of chromosome XI
      of Saccharomyces cerevisiae revealed a high degree of similarity (> 50%) to
      bovine cytochrome b560, the sdhC polypeptide of the Escherichia coli succinate
      dehydrogenase (SDH) complex and the protein specified by ORF137 located on the
      chloroplast DNA of Marchantia polymorpha. Disruption of the yeast gene severely
      impaired mitochondrial function, while Northern analysis showed it to be subject
      to catabolite repression. Deletion analysis of the CYB3 promoter identified a
      single HAP2/3/4-binding element that is necessary and sufficient for carbon
      source-dependent transcriptional regulation. These experiments also suggested the
      presence of additional, as yet unidentified, transcriptional control elements,
      both negative and positive. Taken together, these data lead us to conclude that
      the CYB3 gene encodes the yeast homolog of the bovine cytochrome b560 component
      of complex II of the mitochondrial electron transport chain.

PMID- 8152422
TI  - The determined state of white expression in the Drosophila eye is modified by
      zeste1 in the wzm family of mutants.
AB  - Analysis of the whitezeste mottled (wzm) mutant family suggests that the zeste
      gene product functions in establishing and stabilizing a transcriptionally active
      chromatin domain for white locus expression. The z1 mutation reduces expression
      of paired or proximate copies of white, while single or unpaired copies maintain
      wild-type levels of expression. The wzm mutation, caused by the insertion of the
      retrotransposon BEL into the 5' intron of white, alters the zeste-white
      interaction to produce a mottled eye phenotype in hemizygous z1 wzm males. We
      have determined the molecular structure of four wzm derivatives. wzl results from
      the insertion of an additional transposable element into the 5' regulatory region
      of white. wzvl is a deletion of sequences upstream of the white locus. Two
      others, whalo and wcres, result from the transposition of wzm plus the entire
      verticals-roughest region into heterochromatin near the tip of chromosome 3L.
      They variegate for roughest but not for white; rather, the z1 effect on wzm now
      causes white expression to become non-autonomous and non-clonal. The analysis of
      these five mutations shows that the neomorphic zeste1 product, in combination
      with structural changes imposed by transposons and intercalary heterochromatin,
      modifies the determination and stability of white expression. We propose that the
      normal zeste product functions as part of a complex that stimulates transcription
      by changing chromatin conformation to establish and maintain transcriptionally
      active domains. The unpairing of homologs is proposed to be one of the initial
      results of conformational change, providing an explanation for the role of zeste
      in transvection.

PMID- 8152423
TI  - The H-NS protein modulates the activation of the ilvIH operon of Escherichia coli
      K12 by Lrp, the leucine regulatory protein.
AB  - The H-NS protein, the product of the hns gene, plays a central role in the
      cellular response of bacteria to environmental stresses such as modification of
      osmolarity and temperature. The leucine regulatory protein (Lrp) controls a wide
      array of operons both as an activator (e.g. ilvIH) and as a repressor. We
      demonstrate that H-NS can decrease the activity of Lrp in stationary phase and
      under conditions of high osmolarity. Strains containing hns mutations have higher
      levels of Lrp-activated ilvIH transcription, while strains carrying the hns+
      allele on a pBR322 plasmid have lower activity of Lrp-directed ilvIH gene
      expression.

PMID- 8152424
TI  - Effect of ogt expression on mutation induction by methyl-, ethyl- and
      propylmethanesulphonate in Escherichia coli K12 strains.
AB  - We have previously reported the isolation of an Escherichia coli K12 mutant that
      is extremely sensitive to mutagenesis by low doses of ethylating agents. We now
      show by Southern analysis that the mutation involves a gross deletion covering at
      least the ogt and fnr genes and that no O6-alkylguanine-DNA-alkyltransferase
      activity is present in cell-free extracts of an ada::Tn10 derivative of these
      bacteria. Confirmation that sensitisation to ethylation-induced mutagenesis was
      attributable to ogt and not to any other loci covered by the deletion was
      obtained by constructing derivatives. Thus an ogt::kanr disruption mutation was
      introduced into the parental ogt+ bacteria, and the ogt::kanr mutation was then
      eliminated by cotransduction of ogt+ with the closely linked Tetr marker
      (zcj::Tn10). The delta(ogt-fnr) deletion or ogt::kanr disruption mutants were
      highly sensitive to ethyl methanesulphonate-induced mutagenesis, as measured by
      the induction of forward mutations to L-arabinose resistance (Arar). Furthermore,
      the number of Arar mutants increased linearly with dose, unlike the case in ogt+
      bacteria, which had a threshold dose below which no mutants accumulated.
      Differences in mutability were even greater with propyl methanesulphonate.
      Overproduction of the ogt alkyltransferase from a multicopy plasmid reduced
      ethylmethanesulphonate-induced mutagenesis in the ogt- mutant strains and also
      methylmethanesulphonate mutagenesis in ada- bacteria. A sample of AB1157 obtained
      from the E. coli K12 genetic stock centre also had a deletion covering the ogt
      and fnr genes. Since such deletions greatly influence the mutagenic responses to
      alkylating agents, a survey of the presence of the ogt gene in the E. coli K12
      strain being used is advisable.

PMID- 8152425
TI  - Pit-1/GH factor-1 involvement in the gene expression of somatolactin.
AB  - A presumed pituitary hormone, somatolactin (SL), belonging to the GH/PRL family,
      is produced in the intermediate lobe of teleost pituitary. The pituitary-specific
      transcription factor, Pit-1, is indispensable not only for the expression of
      mammalian GH and PRL genes, but for the development of GH- and PRL-producing
      cells present in the anterior lobe of the pituitary as well. Thus, in this study,
      examination was made of the possible involvement of Pit-1 in the intermediate
      lobe-specific expression of the SL gene. Using antibodies against chum salmon Pit
      1, the presence of the 40-kilodalton Pit-1 protein in anterior and
      neurointermediate lobes of rainbow trout pituitary was demonstrated. By
      immunohistochemical examination, Pit-1 protein was shown to be located in the
      nuclei of SL-producing cells in the intermediate lobe. In experiments of
      cotransfection into HeLa cells, rat Pit-1 enhanced the promoter activity of SL
      gene, and a 0.5-kilobase upstream region from the transcriptional start site was
      sufficient for this enhancement. It follows from these results that Pit-1 protein
      may possibly be involved in SL gene expression as well as the development of SL
      producing cells.

PMID- 8152426
TI  - Stress-induced regulation of a human proenkephalin-beta-galactosidase fusion gene
      in the hypothalamus of transgenic mice.
AB  - Transgenic mice expressing an Escherichia coli beta-galactosidase reporter gene
      under the control of 3 kilobases of human proenkephalin gene 5'-flanking sequence
      and 1.2 kilobases of 3'-flanking sequence exhibited an anatomically correct
      pattern of basal and stress-regulated transgene expression within the
      hypothalamus. Acute osmotic stress and hypovolemia induced transgene expression
      in neurons within both the paraventricular and supraoptic nuclei. Chronic osmotic
      stress resulted in dramatic induction of transgene expression in both nuclei.
      These results demonstrate that the information required for correct hypothalamic
      expression and stress regulation of the proenkephalin gene is contained within
      our fusion construct.

PMID- 8152427
TI  - Specific repression of rat prolactin gene expression in transplanted tumor cells.
AB  - Transplantation of GH3 rat pituitary tumor cells that express both PRL and GH to
      female Wistar-Furth rats results in tumors that secrete only GH. We have used in
      vivo passage of GH3 cells as a model system to study specific repression of PRL.
      RNA blot hybridization revealed that PRL message was repressed 95% in cells
      transplanted to host animals compared to that in GH3 cells in culture. In
      contrast, there was little change in GH message in the transplanted cells, and
      there was a 4-fold increase in insulin-like growth factor-I transcript levels.
      When the transplanted cells were returned to cell culture, PRL mRNA levels
      increased rapidly, reaching levels similar to those in GH3 cells within 72 h.
      Gene transfer studies demonstrated a low level PRL promoter utilization in GH3
      cells after in vivo passage, when endogenous PRL was repressed. Transfection of
      the transplanted cells maintained in culture for 96 h, when endogenous PRL was
      expressed, demonstrated increased PRL promoter activity. Messenger RNA levels for
      the transcription factor Pit-1 were equivalent in GH3 cells and cells after in
      vivo passage, and the presence of Pit-1 protein in extracts from transplanted
      cells was demonstrated by Western blot analysis. Electrophoretic gel mobility
      shift assays indicated that protein interactions with the PRL promoter were very
      different for extracts prepared from cells in which PRL was repressed compared to
      those from cells maintained in culture until PRL expression had
      recovered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152428
TI  - Human estrogen receptor transactivational capacity is determined by both cellular
      and promoter context and mediated by two functionally distinct intramolecular
      regions.
AB  - We have used a series of human estrogen receptor (ER) mutants to evaluate the
      cell- and promoter-specific transcriptional activities of the TAF1 and TAF2
      transactivation regions within the human ER. We show that the manifestation of
      TAF1 or TAF2 function depends strongly upon promoter context; on certain
      promoters, both the TAF1 and TAF2 activators are required for wild-type
      transcriptional activity, whereas on other promoters, the TAF1 and TAF2
      activators function independently. Using these constructs, we show that the
      antagonist activity of the triphenylethylene-derived antiestrogens, e.g.
      tamoxifen, arises from their intrinsic inability to activate ER TAF2 function.
      However, on certain promoters, these antiestrogens efficiently activate gene
      transcription through ER. Consistent with this observation, the TAF2 function of
      the ER is not required on all promoters. In these TAF2-independent promoter
      contexts, TAF2 function may be provided by a separate transcription factor bound
      to the promoter. These data suggest that 1) TAF1 may be the major transcriptional
      activator of the ER; and 2) TAF2 functions as a transcriptional facilitator. On
      promoters where TAF2 function is provided independently of the ER, the TAF1
      function of the ER can function independently of TAF2 activity, allowing
      triphenylethylene-derived antiestrogens to demonstrate partial agonist activity.
      These observations provide a possible molecular explanation for the tissue
      specific partial agonist properties of tamoxifen and related triphenylethylene
      antiestrogens observed in vivo.

PMID- 8152429
TI  - Ordered binding of retinoic acid and retinoid-X receptors to asymmetric response
      elements involves determinants adjacent to the DNA-binding domain.
AB  - Retinoic acid, a pleiotropic regulator of development and homeostasis, controls
      the expression of specific gene networks via direct interactions with nuclear
      receptors. The retinoic acid receptor (RAR), as a heterodimer with the retinoid-x
      receptor (RXR), binds to DNA recognition sites, referred to as retinoic acid
      response elements (RAREs), that are generally composed of a direct repeat of the
      half-site core motif PuGGTCA spaced by 2 (DR-2) or 5 (DR-5) basepairs. The
      asymmetric nature of direct repeat RAREs suggests that RAR and RXR bind
      preferentially to one of the two half-site core motifs. Here we show that RXR
      occupies the 5'-up-stream half-site, and RAR the 3'-down-stream half-site of the
      direct repeat in both DR-2 and DR-5 RAREs. We also demonstrate that a region
      adjacent to the zinc finger region of RAR and RXR is essential for specific and
      cooperative binding of DNA-binding domain peptides to RAREs. However,
      differential utilization of these determinants mediate RAR-RXR heterodimer
      binding to DR-2 and DR-5 RAREs. The demonstration of ordered but nonequivalent
      binding of RAR-RXR complexes to DR-2 and DR-5 RAREs sets a precedent for the
      generation of sequence specificities in heterodimeric DNA-binding proteins.

PMID- 8152430
TI  - Localization of A-kinase through anchoring proteins.

PMID- 8152431
TI  - Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate
      dependent gene expression.
AB  - Activating transcription factor-3 (ATF-3) is one member of a large family of
      leucine zipper transcription factors which bind to promoters responsive to cAMP
      and phorbol ester at the related cAMP (CRE) and phorbol ester response elements.
      We report here that ATF-3 is coexpressed with the neuropeptide precursor
      proenkephalin in human neuroblastoma SK-N-MC cells. Cotransfection experiments
      indicate that activation of proenkephalin gene expression by ATF-3 is dependent
      upon both the catalytic subunit of the cAMP-dependent protein kinase and the CRE
      2 element. The CRE-2 element is essential for second messenger-inducible
      expression and is known to bind AP-1-like transcription factors. ATF-3 expressed
      in bacteria or from rabbit reticulocyte lysates binds to the proenkephalin CRE-2
      element as a homodimer and as a heterodimer with Jun-D, another activator of
      proenkephalin transcription. ATF-3 stimulates binding of Jun-D to the
      proenkephalin CRE-2 element and acts synergistically with Jun-D to induce
      proenkephalin gene expression. Sequential immunoprecipitations of ATF-3 from SK-N
      MC cells expressing proenkephalin indicate that ATF-3 is complexed with Jun-D in
      vivo and that both proteins are highly phosphorylated. Together, our results
      suggest that ATF-3 may play an important role in the regulation of gene
      expression by cAMP-dependent intracellular signaling pathways.

PMID- 8152432
TI  - Identification of 3',5'-cyclic adenosine monophosphate response element and other
      cis-acting elements in the human androgen receptor gene promoter.
AB  - Androgen and androgen receptor (AR) play an important role in sexual
      differentiation and prostate proliferation. To investigate AR gene
      transcriptional regulation, a 2.3-kilobase AR gene promoter region was isolated,
      sequenced, and characterized. Chloramphenicol acetyltransferase (CAT) assay and
      sequence homology search of AR gene promoter among human, rat, and mouse revealed
      some potential cis-acting elements, including a GC box, a suppressor region, and
      a purine-rich element. Deletion analysis and gel retardation assay using a 50
      base pair (bp) double-strand purine-rich element showed that this purine-rich
      element can bind to specific proteins in nuclear extract of LNCaP and HeLa cells
      and may be essential for AR gene transcription. Furthermore, to investigate the
      effect of cAMP on AR gene transcription, we treated LNCaP and HeLa cells with 10
      mM (Bu)2cAMP after transfection with CAT gene reporter plasmids linked to the AR
      gene promoter. This treatment induced several folds of CAT activity in LNCaP
      cells only, and the induction was further confirmed at AR mRNA level by Northern
      blot analysis and reverse transcription-polymerase chain reaction assay. Deletion
      analysis of the AR gene promoter showed that a region between 530 bp and 380 bp
      upstream of AR gene transcription initiation site, which includes one potential
      cAMP response element (CRE), is responsible for cAMP induction. Gel retardation
      analysis using this CRE (AR/CRE1) showed that AR/CRE1 can bind to specific
      proteins in nuclear extract of LNCaP cells, which appears to form a different
      binding complex compared to somatostatin/CRE.

PMID- 8152433
TI  - Developmental regulation of the thyroid hormone receptor alpha 1 mRNA expression
      in the rat testis.
AB  - The multiplicity of thyroid hormone (TH) effects appears to be mediated by two TH
      receptors (THRs) encoded by two genes, alpha and beta, and, perhaps, by their
      various isoforms. The expression of THR beta is correlated with the presence of
      high affinity binding sites for TH, and all the mutations which cause the
      syndrome of generalized thyroid hormone resistance occur in THR beta. The
      function of THR alpha has not been clearly defined as yet. Another enigma in TH
      action is the effect on the testis. It has been shown that the testis of the
      adult rat does not respond to TH as measured by an increase in oxygen
      consumption. Furthermore, it has not been possible to demonstrate the presence of
      a nuclear high affinity binding site for TH in adult testis. To resolve these
      problems were measured the levels of THR alpha, its nonhormone binding variant,
      and THR beta mRNA in the testis at various stages of development. We discovered
      that the beta-message is absent at all times, whereas the alpha-message is
      expressed only from fetal through prepubertal stages and is absent in adult
      testis. THR alpha, but not the beta-mRNA, was detected in immature Sertoli cells
      in culture, and neither was found in adult Sertoli cell-enriched cultures.
      Furthermore, THR alpha and its variant mRNA was found, using in situ
      hybridization, in the seminiferous cords and seminiferous tubules of fetal and
      prepubertal testis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152434
TI  - Steroidogenic adrenocortical cell lines produced by genetically targeted
      tumorigenesis in transgenic mice.
AB  - Studies of adrenal steroidogenesis have been facilitated by the availability of
      immortalized mouse adrenocortical Y-1 cells. We sought to make new, alternative
      mouse steroidogenic cell lines by genetically targeted tumorigenesis. Transgenic
      mice were constructed expressing both the SV40 T-antigen and a bacterial neomycin
      resistance gene under the control of the promoter for the human P450 cholesterol
      side-chain cleavage (P450scc) gene, which encodes the first and rate-limiting
      enzyme in steroidogenesis. Two female transgenic mice expressed T-antigen in
      various nonsteroidogenic tissues but generated tumors only in the adrenals,
      suggesting adrenal tumor formation was an early event. Ovarian tissues, which,
      unlike the adrenal, do not make steroids in fetal or early postnatal life, did
      not develop tumors. Cell lines derived from the adrenal tumors were resistant to
      the neomycin analog G418. Clonal sublines are stable, growing easily in
      monolayers with a doubling time of 24-60 h. The cell lines secrete progesterone
      and 11-deoxycorticosterone, indicating these cells express the P450scc system, 3
      beta-hydroxysteroid dehydrogenase, and 21-hydroxylase activity. However the 21
      hydroxylase activity was not mediated by P450c21, as the cells lacked P450c21
      mRNA. The cells did not secrete any 11-hydroxylated steroids, although they
      contained P450c11 beta mRNA. Both the secretion of progesterone and the abundance
      of P450scc mRNA increase in response to 8-bromo-cAMP, but not to ACTH or
      angiotensin II. In addition to expression of steroidogenic enzyme mRNAs, one cell
      line also expresses mouse renin-1 mRNA, making these cells useful for studies of
      the role of adrenal renin in regulating adrenal steroidogenesis. These findings
      represent an approach in transgenic mice to develop highly differentiated adrenal
      cell lines.

PMID- 8152435
TI  - HLA-B27 binding peptides derived from the 57 kD heat shock protein of Chlamydia
      trachomatis: novel insights into the peptide binding rules.
AB  - In this study we investigate the 57 kD heat shock protein of Chlamydia
      trachomatis for potential HLA-B27 restricted T cell epitopes. This protein is
      known to elicit T cell immunity, as judged by delayed type hypersensitivity. We
      synthesized 24 peptides containing the B27 anchor amino acid arginine at position
      2, according to the rules previously described for peptide binding to MHC class I
      molecules. The nonamer peptides were tested in an in vitro assembly assay; six
      out of the 24 peptides bind to HLA-B27 although their sequences only partially
      match the HLA-B27 binding motif. Two of these six peptides carry negatively
      charged amino acids which apparently fit into the P1 pocket and in three out of
      the six a positively charged amino acid fits into the P3 pocket. In addition, two
      octamer peptides stabilized the HLA-B27 molecule without containing an
      appropriate amino or carboxy terminus. Therefore our data suggest that current
      binding rules will need to be refined before they can be used to accurately
      predict potential T cell epitopes. Furthermore our HLA-B27-binding peptides
      should prove useful probes for the study of the processing and presentation of
      this bacterial antigen, and of changes in the T cell repertoire induced by this
      form of infection.

PMID- 8152436
TI  - Isolation of a carp complement protein homologous to mammalian factor D.
AB  - Factor D of carp (Cyprinus carpio) complement was purified to apparent
      homogeneity by a 4-step chromatographic procedure and examined for
      physicochemical and functional properties. Carp factor D proved to be an alpha
      globulin with a molecular mass of 29 kDa and the serum concentration was
      estimated to be 6 micrograms/ml. The NH2-terminal amino acid sequence (30
      residues including five unidentified positions) of carp factor D showed high
      homologies (57-60%) to those of mammalian factor D. Neither functional
      compatibility nor common antigenicity was observed between carp and human factor
      D. This report is apparently the first description on the factor D molecule in a
      non-mammalian species.

PMID- 8152437
TI  - The antigen-specific immunoglobulin G receptor is more sensitive to stimulation
      than the IgM receptor in transfected B cells.
AB  - A murine lymphoma cell line (M12.4) was transfected with immunoglobulin (Ig)
      genes encoding a T15+ (idiotype) IgM antibody or an idiotypically identical IgG
      antibody. Three transfectant clones of each class which showed similar (albeit
      distinguishable) levels of membrane expression of the transfected genes were used
      in the study. The response of each cell population to stimulation with anti-T15
      antibodies was followed by measurement of the change in the intracellular Ca++
      concentration. The IgG transfectants were found to be significantly more
      responsive to such stimulation than the IgM cells. In contrast, there was no
      difference in their response to a nonspecific reagent, the calcium ionophore
      A23187.

PMID- 8152438
TI  - Production of anti-phosphorylcholine antibodies of the T15 idiotype in CBA/N xid
      mice: investigation of the defect using a T15 immunoglobulin transgene.
AB  - A notable defect in CBA/N xid mice is their relative inability to make antibodies
      to phosphorylcholine (PC), particularly those of the T15 idiotype which
      predominate in the anti-PC responses of immunologically normal mice. To
      investigate the basis of this defect, we introduced functionally rearranged genes
      encoding a T15+ PC-binding immunoglobulin G antibody into the germline of these
      animals. Expression of these genes in the xid cells was observed, shown by the
      existence of a distinct population of T15+ cells (3 x 10(6)) in the spleen of the
      transgenic animals, and the presence of PC-binding T15+ IgG antibodies (1-15
      micrograms/ml) in the serum. Mixed antibody molecules were also found, however,
      which were composed of both transgene-encoded and endogenously-derived chains.
      Existence of the T15+ cells in these animals seemed normal, since these were not
      depleted (to any great extent) and were immunocompetent as well. The latter was
      shown by the increased T15+ antibody production in the transgenic animals when
      stimulated with a PC-associated thymus-independent type 1 (TI-1) antigen and anti
      idiotype antibodies, but not with the pneumococcal TI-2 antigen. This is similar
      to the PC-specific (T15-) responsiveness of normal CBA/N xid mice. Based on these
      results, we argue that a reason why T15+ antibodies are not normally made by
      CBA/N xid animals is because T15+ genes are not utilized or, as with any T15+
      precursors present, selected for in these animals, in contrast to normal mice
      where the Lyb-5 or CD5 cells (which are absent in CBA/N xid animals) are known to
      be specially endowed to make such antibodies.

PMID- 8152439
TI  - Specificity of antipeptide antibodies produced against V2 and V3 regions of the
      external envelope of human immunodeficiency virus type 2.
AB  - The V2 region of simian immunodeficiency virus (SIV) and V3 region of human
      immunodeficiency virus type 1 (HIV-1) have been reported to be neutralization
      epitopes. We analysed the corresponding regions in HIV-2. Synthetic peptides
      modeling the V2 (aa 149-168) and V3 (CV3: aa 298-315 and NV3: aa 306-324) regions
      of the HIV-2 external envelope glycoprotein were coupled to KLH and used as
      immunogens in rabbits. We characterized the resulting antiV2 and antiV3
      antibodies for their ability to recognize native and deglycosylated HIV-2
      envelope glycoprotein, to block gp-CD4 interaction and to inhibit syncytium
      formation in vitro. The three synthetic peptides induced antibodies able to
      recognize specifically the native HIV-2 envelope glycoprotein with a significant
      avidity (K0.5 between 6 x 10(-7) and 8 x 10(-9) M). Interestingly, the reactivity
      of antibodies produced against the V2 peptide, which contains two potential sites
      of N-glycosylation, was higher against the fully deglycosylated than glycosylated
      HIV-2 external envelope glycoprotein (gp105). The antipeptide antibodies were
      used to investigate the topography of these regions in the preformed gp-CD4
      complex in indirect immunofluorescence assays. The V2 and V3 regions in the
      complex remained accessible to their respective antibodies. Moreover,
      preincubation of gp105 with anti V2 or anti V3 antibodies did not prevent gp-CD4
      interaction. Thus the V2 and V3 regions are not directly involved in the gp105
      binding site for the CD4 receptor. Finally, in contrast with results obtained
      with antibodies produced against the V3 region of HIV-1 gp120 and monoclonal
      antibodies produced against the V3 of SIV, antibodies produced against V2 and V3
      of HIV-2 were unable to inhibit syncytium formation induced by HIV-2 in vitro.

PMID- 8152440
TI  - Humanization of a mouse anti-human interleukin-6 receptor antibody comparing two
      methods for selecting human framework regions.
AB  - Mouse monoclonal antibody AUK12-20 binds to human IL-6 receptor and inhibits IL-6
      functions. It has been humanized by CDR-grafting for therapeutic use. In the
      design of reshaped human AUK12-20 VL region, the human framework regions (FRs)
      from the human Bence-Jones protein REI were used. The reshaped human AUK12-20
      light chain, in combination with chimeric AUK12-20 heavy chain, bound to antigen
      as well as chimeric AUK12-20 antibody. In the design of reshaped human AUK12-20
      VH region, two sets of the human FRs were chosen and compared. One set was from
      the consensus amino acid sequence for human VH regions subgroup (HSG)-I and the
      other set was from human antibody HAX, the most similar human VH region found in
      a database of human immunoglobulin sequences. The HSG-I-based and the HAX-based
      reshaped human AUK12-20 heavy chains in combination with the reshaped human AUK12
      20 light chain, showed approximately 90 and 100% antigen-binding and competition
      binding activities as compared to the chimeric or mouse AUK12-20 heavy chains.
      Most importantly, these humanized antibodies inhibited the IL-6-dependent tumor
      cell growth as well as the original mouse antibody suggesting that these
      humanized antibodies could be efficacious in human patients. Our results show
      that both approaches for the design of reshaped human antibodies can be used for
      successful humanization. The approach based on FRs from the most similar
      individual human antibody, however, seemed to be best for designing a reshaped
      human antibody that mimicked as closely as possible the original mouse antibody.

PMID- 8152441
TI  - Human splenic IgM immunoglobulin transcripts are mutated at high frequency.
AB  - Human spleen immunoglobulin gene rearrangements that used the VH6 gene and were
      expressed with IgM were characterized for their frequency of somatic
      hypermutation from PCR amplified spleen cDNA. A high frequency of rearrangements
      that were somatically mutated was demonstrated by restriction endonuclease
      analysis and sequencing of cloned rearrangements. The 24 rearrangements cloned
      from three different spleens had an overall mutation frequency of 3.1%
      mutations/bp sequenced and ranged from 0.4 to 6.0%. These mutations appeared to
      have been antigenically selected based on both the high frequency and high amino
      acid replacement to silent (R/S) ratios in the complementarity determining
      regions. Five clones that arose from two different rearrangements showed evidence
      of intraclonal diversification with both shared and unique mutations. The mutated
      clones of one spleen donor were lower in frequency and were not concentrated in
      the CDR, which suggested these mutations had not been antigenically selected.
      These findings support the dissociation of somatic mutation and isotype switching
      and the possibility that IgM-expressing B cells may serve as human memory B
      cells.

PMID- 8152442
TI  - Interaction between streptococcal protein Arp and different molecular forms of
      human immunoglobulin A.
AB  - Protein Arp, the IgA-binding protein of the group A Streptococcus, has affinity
      for the Fc-part of IgA. The binding between protein Arp and several different
      molecular forms of human IgA was characterized. It was found that protein Arp
      bound with higher affinity to uncomplexed forms of IgA than to complexed forms
      (secretory IgA, alpha 1-antitrypsin-IgA and alpha 1-microglobulin-IgA). Thus, the
      affinity constant was 2.0-5.9 x 10(8) M-1 for the binding to monomeric, dimeric,
      trimeric, and quadrimeric IgA, and 4.5-5.0 x 10(7) M-1 for binding to the
      complexed forms. Among the uncomplexed IgA-molecules, the affinity constant was
      in the same range for J chain-containing forms (dimeric, trimeric and quadrimeric
      IgA) as for forms without J chain (monomeric and a particular quadrimeric IgA
      devoid of J chain). Western blotting demonstrated that protein Arp bound
      exclusively to the alpha-chain of all IgA-forms. Several lines of evidence
      pointed to a localization of the binding site to the C alpha 3-domain. First,
      protein Arp did not bind to three N-terminal alpha-chain fragments which lacked a
      region corresponding to the C alpha 3-domain, including that form a four-chain
      myeloma IgA, naturally occurring in plasma. Second, the binding to dimeric and
      tri/quadrimeric IgA was partially blocked by an added secretory component, which
      has been suggested to bind to the C alpha 2- and C alpha 3-domains of the alpha
      chain. Finally, alpha 1-antitrypsin and alpha 1-microglobulin, in the weakly
      binding IgA-complexes, have been shown to be linked to the C alpha 3-domain via
      the penultimate amino acid residue of the alpha-chain peptide, supporting the
      hypothesis of a localization of the binding site of protein Arp to the C alpha 3
      domain.

PMID- 8152443
TI  - Target cell-directed degradation of perforin mRNA in CTL: lack of correlation
      with loss of protein and lytic ability.
AB  - We have previously shown that CTL and NK cells rapidly down regulate perforin
      mRNA and become functionally inactive within 4-6 hr after exposure to sensitive
      target cells (TC). We report here for the first time that CTL also down regulate
      perforin mRNA upon exposure to resistant, but binding, TC. When three separate
      human MHC-restricted CTL lines were exposed to resistant TC, perforin mRNA was
      rapidly degraded. Removal of both extracellular Ca++ and Mg++ prevented perforin
      message down regulation, whereas removal of Ca++ alone did not, indicating that
      CTL:TC binding was required. Unlike the response of CTL exposed to sensitive TC,
      resistant TC did not trigger serine esterase (SE) release, suggesting distinct
      signalling pathways for perforin mRNA down regulation and granule exocytosis.
      Moreover, using western analysis, we showed that there was limited (< 10%)
      perforin protein release after CTL:TC interaction, suggesting that CTL loss of
      lytic activity after exposure to sensitive TC is not due to massive depletion of
      perforin. Treatment of CTL with mAb to CD2, CD3, CD2 + CD3, CD8, Class I and LFA
      1 did not induce perforin mRNA down regulation. Furthermore, mAb to CD2, CD3,
      CD8, Class I, Class II, CD54 and LFA-1 did not block TC-mediated perforin mRNA
      down regulation although lysis of TC was inhibited.

PMID- 8152444
TI  - Chemosensitivity and perception of dyspnea in patients with a history of near
      fatal asthma.
AB  - BACKGROUND: Many deaths from attacks of asthma may be preventable. However, the
      difficulty in preventing fatal attacks is that not all the pathophysiologic risk
      factors have been identified. METHODS: To examine whether dyspnea and
      chemosensitivity to hypoxia and hypercapnia are factors in fatal asthma attacks,
      we studied 11 patients with asthma who had had near-fatal attacks, 11 patients
      with asthma who had not had near-fatal attacks, and 16 normal subjects. Their
      respiratory responses to hypoxia and hypercapnia, determined by the standard
      rebreathing technique while the patients were in remission, were assessed in
      terms of the slopes of ventilation and airway occlusion pressure as a function of
      the percentage of arterial oxygen saturation and end-tidal carbon dioxide
      tension, respectively. The perception of dyspnea was scored on the Borg scale
      during breathing through inspiratory resistances ranging from 0 to 30.9 cm of
      water per liter per second. RESULTS: The mean (+/- SD) hypoxic ventilatory
      response (0.14 +/- 0.12 liter per minute per percent of arterial oxygen
      saturation) and airway occlusion pressure (0.05 +/- 0.05 cm of water per percent
      of arterial oxygen saturation) were significantly lower in the patients with near
      fatal asthma than in the normal subjects (0.60 +/- 0.35, P < 0.001, and 0.16 +/-
      0.08, P < 0.001, respectively) and the patients with asthma who had not had near
      fatal attacks (0.46 +/- 0.29, P = 0.003, and 0.15 +/- 0.09, P = 0.004). The Borg
      score was also significantly lower in the patients with near-fatal asthma than in
      the normal subjects, and their lower hypoxic response was coupled with a blunted
      perception of dyspnea. CONCLUSIONS: Reduced chemosensitivity to hypoxia and
      blunted perception of dyspnea may predispose patients to fatal asthma attacks.

PMID- 8152445
TI  - Progression of aortic dilatation and the benefit of long-term beta-adrenergic
      blockade in Marfan's syndrome.
AB  - BACKGROUND: The aortic root enlarges progressively in Marfan's syndrome, and this
      enlargement is associated with aortic regurgitation and dissection. Long-term
      treatment with beta-adrenergic blockade, by reducing the impulse (i.e., the rate
      of pressure change in the aortic root) of left ventricular ejection and the heart
      rate, may protect the aortic root. METHODS: We conducted an open-label,
      randomized trial of propranolol in adolescent and adult patients with classic
      Marfan's syndrome (32 treated and 38 untreated [control] patients). Aortic-root
      dimensions and clinical end points (aortic regurgitation, aortic dissection,
      cardiovascular surgery, congestive heart failure, and death) were monitored for
      an average of 9.3 years in the control group and 10.7 years in the treatment
      group. All 70 patients were included in the analysis according to the intention
      to-treat principle. RESULTS: The dose of propranolol was individualized; the mean
      (+/- SE) dose was 212 +/- 68 mg per day. The mean slope of the regression line
      for the aortic-root dimensions, which reflect the rate of dilatation, was
      significantly lower in the treatment group than in the control group (0.023 vs.
      0.084 per year, P < 0.001). Clinical end points were reached in five patients in
      the treatment group and nine in the control group. The Kaplan-Meier survival
      curve for the treatment group differed significantly from that for the control
      group during the middle years of the trial and remained better for the treatment
      group throughout the study. CONCLUSIONS: Prophylactic beta-adrenergic blockade is
      effective in slowing the rate of aortic dilatation and reducing the development
      of aortic complications in some patients with Marfan's syndrome.

PMID- 8152446
TI  - Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC
      Study Group.
AB  - BACKGROUND: Ursodiol (ursodeoxycholic acid) therapy leads to major improvements
      in patients with primary biliary cirrhosis. The benefit of long-term treatment is
      uncertain. METHODS: We randomly assigned 145 patients with biopsy-proved primary
      biliary cirrhosis to receive ursodiol (13 to 15 mg per kilogram of body weight
      per day) (72 patients) or placebo (73 patients). After two years of follow-up,
      because of the benefit from ursodiol, all patients completing the study received
      ursodiol in an open trial and were monitored for two more years. The end points
      in the assessment of efficacy were as follows: progression of disease, as defined
      by the presence of hyperbilirubinemia, variceal bleeding, ascites, or
      encephalopathy; liver transplantation or a referral for that procedure; and liver
      transplantation (or a referral) or death. RESULTS: Disease progressed
      significantly less frequently in the ursodiol group than in the placebo group (P
      < 0.002; relative risk, 0.28; 95 percent confidence interval, 0.12 to 0.63). The
      probability of liver transplantation or a referral for that procedure and the
      probability of transplantation or death were significantly lower in the group
      assigned to ursodiol than in the group assigned to placebo (for transplantation
      alone, P = 0.003; relative risk, 0.21; 95 percent confidence interval, 0.07 to
      0.66; for transplantation or death, P = 0.005; relative risk, 0.32; 95 percent
      confidence interval, 0.14 to 0.74). High bilirubin levels and, to a lesser
      extent, signs of cirrhosis at entry into the trial were predictive of disease
      progression, liver transplantation or a referral, and transplantation or death.
      CONCLUSIONS: Long-term ursodiol therapy slows the progression of primary biliary
      cirrhosis and reduces the need for liver transplantation.

PMID- 8152447
TI  - Brief report: fatal encephalitis due to variant B human herpesvirus-6 infection
      in a bone marrow-transplant recipient.

PMID- 8152448
TI  - Images in clinical medicine. Dissection of the descending thoracic aorta.

PMID- 8152449
TI  - Exercise-induced asthma.

PMID- 8152450
TI  - Second-line drug therapy for rheumatoid arthritis.

PMID- 8152451
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 19-1994. A 47-year-old woman with long-standing intermittent
      abdominal pain, vomiting, and marked weight loss.

PMID- 8152452
TI  - Blunted perception and death from asthma.

PMID- 8152453
TI  - Marfan's syndrome and other disorders of fibrillin.

PMID- 8152454
TI  - Primary biliary cirrhosis--a first step in prolonging survival.

PMID- 8152455
TI  - Sexual harassment.

PMID- 8152456
TI  - Sexual harassment.

PMID- 8152457
TI  - Sexual harassment.

PMID- 8152458
TI  - Entrapment neuropathies of the upper extremities.

PMID- 8152459
TI  - Entrapment neuropathies of the upper extremities.

PMID- 8152460
TI  - Entrapment neuropathies of the upper extremities.

PMID- 8152461
TI  - Irritable bowel syndrome.

PMID- 8152462
TI  - Active compression-decompression cardiopulmonary resuscitation.

PMID- 8152463
TI  - Active compression-decompression cardiopulmonary resuscitation.

PMID- 8152464
TI  - Borderline systolic hypertension.

PMID- 8152465
TI  - Intravenous immune globulin for dermatomyositis.

PMID- 8152466
TI  - Evaluating drugs after their approval for clinical use.

PMID- 8152467
TI  - A potential hazard of prolonged insertion of an intrauterine device.

PMID- 8152468
TI  - Formation of haematopoietic microenvironment and haematopoietic stem cells from
      single human bone marrow stem cells.

PMID- 8152469
TI  - Instant legislation.

PMID- 8152470
TI  - How to lose confidence.

PMID- 8152471
TI  - Genome research consortium backed.

PMID- 8152472
TI  - UK parliament passes surprise ban on fetal embryos in IVF.

PMID- 8152473
TI  - BASF opens biotech laboratory in the US.

PMID- 8152474
TI  - Cancer institute to tighten control of trials.

PMID- 8152475
TI  - Haemophiliacs seek charges in AIDS scandal.

PMID- 8152476
TI  - Shake-up urged for UK public research labs.

PMID- 8152478
TI  - Triplet repeat genes raise questions.

PMID- 8152477
TI  - Mystery of the poisoned expedition.
AB  - The Burke and Wills expedition through the interior of Australia in the
      nineteenth century ended in calamity. But the cause of death was more pernicious
      than anyone at the time had imagined: beriberi due to thiaminase poisoning.

PMID- 8152479
TI  - Evolutionary biology. The eye in a twinkling.

PMID- 8152480
TI  - Drug design. Reflections on a peptide.

PMID- 8152481
TI  - Endothelin-1. A matter of life and breath.

PMID- 8152482
TI  - Elevated blood pressure and craniofacial abnormalities in mice deficient in
      endothelin-1.
AB  - The endothelin-1 (ET-1) gene was disrupted in mouse embryonic stem cells by
      homologous recombination to generate mice deficient in ET-1. These ET-1-/-
      homozygous mice die of respiratory failure at birth and have morphological
      abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs. ET
      1+/- heterozygous mice, which produce lower levels of ET-1 than wild-type mice,
      develop elevated blood pressure. These results suggest that ET-1 is essential for
      normal mouse development and may also play a physiological role in cardiovascular
      homeostasis.

PMID- 8152483
TI  - Three-dimensional structure of a human class II histocompatibility molecule
      complexed with superantigen.
AB  - The structure of a bacterial superantigen, Staphylococcus aureus enterotoxin B,
      bound to a human class II histocompatibility complex molecule (HLA-DR1) has been
      determined by X-ray crystallography. The superantigen binds as an intact protein
      outside the conventional peptide antigen-binding site of the class II major
      histocompatibility complex (MHC) molecule. No large conformational changes occur
      upon complex formation in either the DR1 or the enterotoxin B molecules. The
      structure of the complex helps explain how different class II molecules and
      superantigens associate and suggests a model for ternary complex formation with
      the T-cell antigen receptor (TCR), in which unconventional TCR-MHC contacts are
      possible.

PMID- 8152484
TI  - Axonal sprouting accompanies functional reorganization in adult cat striate
      cortex.
AB  - Removal of sensory input from a focal region of adult neocortex can lead to a
      large reorganization of cortical topography within the deprived area during
      subsequent months. Although this form of functional recovery is now well
      documented across several sensory systems, the underlying cellular mechanisms
      remain elusive. Weeks after binocular retinal lesions silence a corresponding
      portion of striate cortex in the adult cat, this cortex again becomes responsive,
      this time to retinal loci immediately outside the scotoma. Earlier findings
      showed a lack of reorganization in the lateral geniculate nucleus and an
      inadequate spread of geniculocortical afferents to account for the cortical
      reorganization, suggesting the involvement of intrinsic cortical connections. We
      investigated the possibility that intracortical axonal sprouting mediates long
      term reorganization of cortical functional architecture. The anterograde label
      biocytin was used to compare the density of lateral projections into reorganized
      and non-deprived cortex. We report here that structural changes in the form of
      axonal sprouting of long-range laterally projecting neurons accompany topographic
      remodelling of the visual cortex.

PMID- 8152485
TI  - A molecular switch activated by metabotropic glutamate receptors regulates
      induction of long-term potentiation.
AB  - Pharmacological studies of long-term potentiation (LTP) in the hippocampus are
      starting to provide a molecular understanding of synaptic plastic processes which
      are believed to be important for learning and memory in vertebrates. In the CA1
      region of the hippocampus, the synaptic activation of glutamate receptors of the
      N-methyl-D-aspartate (NMDA) subtype is necessary for the induction of LTP under
      most experimental conditions. The synaptic activation of metabotropic glutamate
      receptors (mGluRs) is also needed for the induction of LTP. We now show that the
      role of mGluRs in the induction of LTP is fundamentally different from that of
      NMDA receptors. NMDA receptors initiate a molecular event that needs to be
      triggered each time a tetanus is delivered to induce LTP. In contrast, mGluRs
      activate a molecular switch which then negates the need for mGluR stimulation
      during the induction of LTP. This mGluR-activated switch is input-specific and
      can be turned off by a train of low-frequency stimulation. The molecular switch
      is a new feature of LTP which has fundamental consequences for our understanding
      of synaptic plastic mechanisms.

PMID- 8152486
TI  - A rationally designed CD4 analogue inhibits experimental allergic
      encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune
      disease of the central nervous system that can be elicited in rodents and is the
      major animal model for the study of multiple sclerosis (MS). The pathogenesis of
      both EAE and MS directly involves the CD4+ helper T-cell subset. Anti-CD4
      monoclonal antibodies inhibit the development of EAE in rodents, and are
      currently being used in human clinical trials for MS. We report here that similar
      therapeutic effects can be achieved in mice using a small (rationally designed)
      synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical
      incidence and severity of EAE with a single injection, but does so without
      depletion of the CD4+ subset and without the inherent immunogenicity of antibody.
      Furthermore, this analogue is capable of exerting its effects on disease even
      after the onset of symptoms.

PMID- 8152487
TI  - Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human
      cancers.
AB  - Cytogenetic abnormalities of chromosome 9p21 are characteristic of malignant
      melanomas, gliomas, lung cancers and leukaemias. From a panel of 46 human
      malignant cell lines, we localized by positional cloning the most frequently
      deleted region on 9p21. Sequence analysis of the isolated fragment reveals two
      open reading frames identical to the recently described complementary DNA for the
      inhibitor of cyclin-dependent kinase 4 (CDK4). Polymerase chain reaction and
      Southern blot analysis confirmed the frequent deletion or rearrangement of the
      CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the
      absence of detectable gene transcripts. One carcinoma had a deletion entirely
      within the CDK4-inhibitor gene. The CDK4-inhibitor gene from a patient with
      dysplastic nevus syndrome had a germ-line nonsense mutation. The CDK4 inhibitor
      is thought to be a physiological suppressor of proliferation. Cells unable to
      produce the inhibitor may be prone to neoplastic transformation.

PMID- 8152488
TI  - Pancreatic islet cell toxicity of amylin associated with type-2 diabetes
      mellitus.
AB  - The 37-amino-acid polypeptide amylin is the principal constituent of the amyloid
      deposits that form in the islets of Langerhans in patients with type-2 diabetes
      mellitus, but its role in the pathogenesis of this disease is unresolved. In view
      of the fact that the beta-amyloid protein that forms fibrils in Alzheimer's
      disease is toxic to neurons, we have investigated whether amylin fibrils could be
      toxic to pancreatic islet cells. We show here that human amylin is toxic to
      insulin-producing beta-cells of the adult pancreas of rats and humans. This
      toxicity is mediated by the fibrillar form of the amylin peptide and requires
      direct contact of the fibrils with the cell surface. The mechanism of cell death
      involves RNA and protein synthesis and is characterized by plasma membrane
      blebbing, chromatin condensation and DNA fragmentation, indicating that amylin
      induces islet cell apoptosis. These findings indicate that amylin fibril
      formation in the pancreas may cause islet cell dysfunction and death in type-2
      diabetes mellitus.

PMID- 8152489
TI  - Calcium/calmodulin inhibition of basic-helix-loop-helix transcription factor
      domains.
AB  - The ubiquitous Ca(2+)-binding protein calmodulin (CaM) is a key protein in Ca2+
      homeostasis and activation of eukaryotic cells. CaM is the molecular link between
      free Ca2+ in the cell and the inhibition, or activation, of numerous enzymes.
      Many nuclear functions are under Ca2+/CaM control, and some transcriptional
      activators are known to be Ca2+ modulated indirectly through Ca2+/CaM-dependent
      protein kinases. But Ca2+/CaM has not yet been found to directly modulate any
      transcription factor or other DNA-binding protein. Transcription factors of the
      basic-helix-loop-helix (bHLH) group are important regulators in numerous systems.
      Here we report that binding of Ca(2+)-loaded CaM to the bHLH domains of several
      bHLH proteins directly inhibits their DNA binding. Other bHLH proteins are either
      less sensitive or resistant. Ca2+ ionophore selectively inhibits transcriptional
      activation by Ca2+/CaM-sensitive bHLH proteins in vivo, implying that Ca2+ can
      directly influence transcription through differential CaM inhibition of bHLH
      domains.

PMID- 8152490
TI  - Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase
      II.
AB  - The RNA polymerase II general transcription factor TFIIH is composed of several
      polypeptides. The observation that the largest subunit of TFIIH is the excision
      repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair
      disorders xeroderma pigmentosum (XP) and Cockayne's syndrome, suggests a
      functional link between transcription and DNA repair. To understand the
      connection between these two cellular processes, we have extensively purified and
      functionally analysed TFIIH. We find that TFIIH has a dual role, being required
      for basal transcription of class II genes and for participation in DNA-excision
      repair. TFIIH is shown to complement three different cell extracts deficient in
      excision repair: XPB/ERCC3, XPC and XPD/ERCC2. The complementation of XPB and XPD
      is a consequence of ERCC3 and ERCC2 being integral subunits of TFIIH, whereas
      complementation of XPC is due to an association of this polypeptide with TFIIH.
      We found that the general transcription factor IIE negatively modulates the
      helicase activity of TFIIH through a direct interaction between TFIIE and the
      ERCC3 subunit of TFIIH.

PMID- 8152491
TI  - Your future in your hands.

PMID- 8152492
TI  - [Psychopathological symptoms in children of war victims].

PMID- 8152493
TI  - [Refugees who experienced violence and the family practitioner].

PMID- 8152494
TI  - [Health problems in refugees of former Yugoslavia in temporary refugee centers in
      The Netherlands].

PMID- 8152495
TI  - [Medical consequences of land mines: Red Cross experiences].
AB  - OBJECTIVE: To describe the medical consequences of land mine injuries. DESIGN:
      Retrospective study. METHOD: A total of 17,414 casualties of war, treated in five
      hospitals of the International Committee of the Red Cross (ICRC) over a three
      year period were evaluated. 3264 of these casualties had anti-personnel mine
      injuries. RESULTS: Approximately one out of three land mine casualties underwent
      an amputation of the lower extremities (n = 1040). The number of operations and
      the blood requirements depended on the extent of the amputation. Hospital
      mortality was 3.8%. CONCLUSION: Amputees have a higher mortality and a longer
      hospital stay, need more blood and undergo more operations than non-amputated
      casualties. The social consequences are considerable, as well. Better protection
      against indiscriminate use of anti-personnel mines is urgently necessary on
      medical grounds.

PMID- 8152496
TI  - [Treatment of spontaneous pneumothorax: survey among Dutch pneumonologists].
AB  - OBJECTIVE: To gain insight into the treatment of spontaneous pneumothorax in the
      Netherlands. DESIGN: Questionnaire. SETTING: Nationwide in the Netherlands.
      METHOD: A questionnaire was sent to all 286 practising pulmonologists in the
      Netherlands to inquire about the mode of treatment used for spontaneous
      pneumothorax. Answers were sorted by size of practice. University hospital, non
      university hospitals qualified for residency training and offices with at least 4
      pulmonologists were classified as large practices. Other practices were
      classified as small. RESULTS: 89% of all pulmonologists responded. In small
      practices, a first spontaneous pneumothorax was treated by chest tube drainage;
      in large practices, thoracoscopy was usually performed. In recurrent
      pneumothorax, thoracoscopy was the first choice in both small and large
      practices. The role of interventional thoracoscopy and surgery was not
      established. CONCLUSION: Worldwide, including in the Netherlands, there is no
      consensus about the treatment of spontaneous pneumothorax. Randomised studies
      with cost-effect analysis are necessary.

PMID- 8152497
TI  - [Correction of the external ear using cartilage-sparing techniques].
AB  - OBJECTIVE: To establish the value of cartilage sparing suture techniques for
      correction of prominent ears. DESIGN: Retrospective study. LOCATION: Gooi-Noord
      Hospital, Blaricum, the Netherlands. METHOD: Between 1989 and 1992, 117 ears in
      62 patients were corrected for prominence. Results were evaluated using the
      McDowell criteria for anatomy and localisation of the ear. RESULTS: Of 117 ears
      108 were corrected successfully. A recurrence was seen in 6 ears and 3 ears
      showed overcorrection. Reoperation was needed in 2 ears. A suture was extruded in
      15 ears, which could be treated relatively easily in 14. CONCLUSION: Cartilage
      sparing suture techniques for correction of the specific anatomic deformities of
      prominent ears prove to be successful. Suture extrusion was the most frequent,
      but minor, complication. Suture extrusion appears to be dependent upon suture
      material and localisation.

PMID- 8152498
TI  - [Gallstones in the lesser pelvis following laparoscopic cholecystectomy].
AB  - A woman aged 45 years who had undergone laparoscopic cholecystectomy a little
      over one year previously complained of progressive dysmenorrhoea, dyspareunia and
      disorder of the cycle; she also had palpable nodules in the recto-uterine pouch.
      At vaginal hysterectomy, 15 gallstones were found in the recto-uterine and
      vesicouterine pouches. Problems of radiological diagnosis in cases of gallstones
      in the true pelvis after laparoscopic cholecystectomy have been reported before.

PMID- 8152499
TI  - [Medical opinions and legal argumentation in war and resistance victims].

PMID- 8152500
TI  - [Report of 2 train trips with displaced persons from former Yugoslavia].

PMID- 8152501
TI  - [Report from Bosnia].

PMID- 8152502
TI  - [Folic acid for all women desiring a child: wrong advice].

PMID- 8152503
TI  - [Disturbing admission numbers for schizophrenia in migrants from Surinam, the
      Netherlands Antilles and Morocco].

PMID- 8152504
TI  - [Hypertension caused by arterial fibromuscular dysplasia].

PMID- 8152505
TI  - [Single blood pressure determination in a follow-up visit for hypertension more
      often leads to management adjustment than multiple measurements].

PMID- 8152506
TI  - [Difference of opinion about tube feeding in a patient with dementia].

PMID- 8152508
TI  - [Neonatal sepsis: not always bacterial].

PMID- 8152507
TI  - [Minor symptoms in family practice, erythrasma].

PMID- 8152509
TI  - [Does latent HIV-infection exist?].

PMID- 8152510
TI  - [Acetylcysteine: a promising antioxidant for cardiorespiratory disorders].

PMID- 8152511
TI  - [Clinical relevance of resistance against cytostatic agents in children with
      leukemia].

PMID- 8152512
TI  - [Imported malaria: epidemiological, clinical and therapeutic data of 74 patients
      during 1 year in the Academic Medical Center, Amsterdam].
AB  - OBJECTIVE: To gain insight into the changes concerning diagnosis and treatment of
      malaria since 1984. DESIGN: Retrospective. SETTING: University Medical Centre,
      Amsterdam. METHOD: From October 1991 to October 1992, 74 patients with malaria
      were diagnosed and treated. Country of origin, plasmodium strain involved,
      country of infection, interval between return to the Netherlands and onset of
      symptoms, prophylaxis and therapy, were recorded in every case. RESULTS: Of these
      patients 46 (62%) were of European origin; 28 were born in endemic malarial
      areas. Plasmodium falciparum was diagnosed in 49 of the 74 patients; 88% of these
      infections were acquired in subsaharan Africa, mainly West Africa. In falciparum
      malaria, the first symptoms were noticed I-30 days after returning home. P. vivax
      infections occurred up to 2 years after return. Five of the 49 patients developed
      severe complications; 2 died. Twenty-six (53%) of the 49 patients had not taken
      any chemoprophylaxis. The patients with falciparum malaria were treated with
      sulfadoxine-pyrimethamine or halofantrine, often combined with quinine; the cure
      rate was 90%. CONCLUSION: Quinine remains the mainstay in the treatment of
      complicated falciparum malaria, but is also often used in the initial treatment
      of uncomplicated malaria. Compliance in malaria prophylaxis still remains a
      problem.

PMID- 8152513
TI  - [Intra-abdominal adhesions and foreign-body granulomas following earlier
      laparotomy].
AB  - OBJECTIVE: To determine the prevalence of foreign body granulomas in intra
      abdominal adhesions in patients subjected to relaparotomy. DESIGN: Cross
      sectional. SETTING: University Hospital Rotterdam-Dijkzigt, the Netherlands.
      METHOD: From July 1991 to September 1992, 119 patients were subjected to
      relaparotomy. Presence, distribution and quality of adhesions were scored during
      the relaparotomy and adhesion samples were taken for histological examination.
      RESULTS: Adhesions were present in 94% of the patients; they were most frequently
      attached to small bowel (83%) and omentum (78%). The number of adhesions was
      significantly smaller in patients with a history of only one minor operation than
      in those with one major or multiple laparotomies. Foreign body granulomas were
      found in 22% of the patients with adhesions. These were caused by suture material
      (19%) or starch glove powder (6%); a combination of both occurred in 3% of the
      patients. When granulomas were present, the median interval between present and
      most recent laparotomy was significantly shorter than when no granulomas were
      found. In patients with adhesions who had had the previous operation less than 6
      months previously, granulomas were present in 71%. In contrast, 13% of the
      patients operated upon longer than 6 months previously had granulomas.
      CONCLUSIONS: In young adhesions foreign body granulomas occur in large
      percentages of the cases. This suggests that the intra-abdominal presence of
      foreign material is an important cause of adhesion formation. Therefore, intra
      abdominal contamination with suture material and glove powder should be avoided.

PMID- 8152514
TI  - [Dysmorphic erythrocytes in urinary sediment in differentiating urological from
      nephrological causes of hematuria].
AB  - OBJECTIVE: To determine the significance of dysmorphic erythrocytes in the
      urinary sediment for discrimination between urological and nephrological causes
      of haematuria. DESIGN: Evaluation of diagnostic test. SETTING: Departments of
      Nephrology and Pathology, University Hospital Nijmegen. METHOD: Of 107 patients
      with haematuria in whom renal parenchymal or urological disease was diagnosed,
      the percentage of dysmorphic erythrocytes was estimated in the unstained urinary
      sediment with normal light microscopy. By using a Receiver Operating
      Characteristic curve the cutoff point that provided the highest diagnostic value
      of the erythrocyte morphology was determined. In addition, the inter-observer
      variation was estimated in a separate series of 26 urinary sediments. RESULTS: At
      a cutoff value of 40% dysmorphic erythrocytes the sensitivity for urological
      pathology was 100% and the specificity 66.7%. When presence of erythrocyte,
      haemoglobin or fatty casts was also considered as a criterion for a nephrological
      diagnosis, the specificity for urological pathology rose to 88.1%. The inter
      observer variation showed a correlation coefficient of 0.90 (kappa: 0.77).
      CONCLUSION: Evaluation of the erythrocyte morphology in the urinary sediment is a
      reliable aid in determining the strategy to be followed in patients with
      haematuria. It is important, however, that strict criteria for establishing
      erythrocyte dysmorphism are applied.

PMID- 8152515
TI  - [2 patients with autosomal recessive generalized myotonia].
AB  - Two men aged 20 and 18 years complained of transient muscle stiffness of 4 and 2
      years' duration, respectively. Symptoms had started in the legs. Gradually, arm
      muscles and eventually facial and pharyngeal muscles became affected.
      Neurological examination revealed myotonia without any associated symptoms.
      Myotonia was confirmed by electromyography. Laboratory investigations, ECG, chest
      X-rays, slit lamp examination in both patients, and muscle biopsy in one,
      revealed no abnormalities. History, physical examination and electromyography of
      family members disclosed no evidence of myotonic dystrophy. Based on the findings
      mentioned, the diagnosis of autosomal recessive generalised myotonia was made.

PMID- 8152516
TI  - [Law on Mass Screening].

PMID- 8152517
TI  - [Conflicting interests of pregnant women and unborn child, especially in
      allochthonous persons].

PMID- 8152518
TI  - [Conflicting interests of pregnant women and unborn child, especially in
      allochthonous persons].

PMID- 8152519
TI  - [Rupture of the pregnant uterus].

PMID- 8152520
TI  - Injection of the protein kinase inhibitor H7 into the A10 dopamine region blocks
      the acute responses to cocaine: behavioral and in vivo microdialysis studies.
AB  - Cocaine produces a motor-stimulant response in part by its actions within the
      mesolimbic dopamine system. Repeated exposure to cocaine induces an augmented
      motor activity response which is termed behavioral sensitization, or reverse
      tolerance. Previous studies have suggested that sensitization may result from
      increased dopamine neuronal activity in the A10 region; the origin of the
      mesolimbic dopamine system. However, the exact mechanisms involved in the
      development of behavioral sensitization remain to be elucidated. Studies on other
      forms of sensitization in the nervous system suggest a critical role for
      increased protein kinase C (PKC) activity in the development of the sensitized
      response. As a first step in examining the role of PKC in cocaine-induced
      behavioral sensitization, the effect of intra-A10 administration of a PKC
      inhibitor, H7, on the acute motor-stimulant response to cocaine was studied.
      Intra-A10 injections of H7 dose-dependently (1.0-30.0 nmol/side) inhibited
      cocaine (15.0 mg/kg)-induced motor activity. Pretreatment with H7 (30.0
      nmol/side) also blocked the cocaine-induced rise of extracellular dopamine in a
      terminal region of the mesolimbic dopamine system, the nucleus accumbens, as
      measured by in vivo microdialysis. These data suggest that activation of protein
      kinases may be important in cocaine-induced motor activity.

PMID- 8152521
TI  - The antinociceptive and motivational effects of intranigral injection of opioid
      agonists.
AB  - The antinociceptive potency of morphine and the morphine metabolite morphine-6
      glucuronide (M6G) was examined after injection into the substantia nigra and
      periaqueductal gray (PAG) of rats. Both drugs produced antinociception in both
      sites. The antinociceptive potency of M6G was significantly greater than morphine
      in the nigra. There was no difference in the antinociceptive potency of M6G in
      the nigra and PAG. M6G and other opioids were also examined for motivational
      effects after intranigral injection. A high dose of intranigral morphine (10.0
      nmol) produced a conditioned place preference. No significant motivational
      effects were produced by 1.0 nmol of M6G, D-Ala2, N-Me-Phe4,Gly5-ol-enkephalin
      (DAGO), D-Pen2,D-Pen5-enkephalin (DPDPE), or U-50,488H. It is concluded that the
      substantia nigra plays an important role in opioid antinociception. The role of
      the nigra in opioid reward is questionable.

PMID- 8152522
TI  - Regional reward differences within the ventral pallidum are revealed by
      microinjections of a mu opiate receptor agonist.
AB  - The ventral pallidum receives a major projection from the nucleus accumbens, a
      heavily studied terminus of the mesolimbic dopamine system that is known to be
      involved in a variety of reward and behavioral functions. Recently, ventral
      pallidum microinjections of the mu opiate receptor agonist Tyr-D-Ala-Gly-NMe-Phe
      Gly-ol-enkephalin (DAMGO) have been shown to increase motor activity while
      ventral pallidum lesions have been shown to reduce opiate and cocaine self
      administration behaviors. These results suggest a possible continuation of the
      mesolimbic reward/motor circuit from the nucleus accumbens into the ventral
      pallidum. This study investigated the effects of ventral pallidum DAMGO
      microinjections on reward and motor/performance through the use of the
      intracranial self-stimulation rate-frequency curve-shift paradigm.
      Microinjections of DAMGO (vehicle, 0.03 nmol, and 0.33 nmol) were administered
      bilaterally in a random dose order with a minimum of 3 days between injections.
      Rats were tested over three consecutive rate-frequency curves immediately
      following the opiate microinjections to investigate the time course of drug
      effects. DAMGO microinjections in the rostral ventral pallidum produced decreases
      in reward and motor/performance when compared to normal baseline activity or
      vehicle microinjections. In contrast, DAMGO microinjections into the caudal
      ventral pallidum produced increases in reward and motor/performance. These data
      confirm a role for the ventral pallidum in limbic function and extend it to
      intracranial self-stimulation reward. They also suggest reward modulation in the
      ventral pallidum is a regionally heterogeneous function and that the rostral
      ventral pallidum may be a transition area between the nucleus accumbens and the
      ventral pallidum.

PMID- 8152523
TI  - Distribution and characterization of the [3H]granisetron-labelled 5-HT3 receptor
      in the human forebrain.
AB  - The present study has demonstrated the distribution of [3H]granisetron-labelled 5
      HT3 receptors in the human forebrain with relatively high levels of this receptor
      in homogenates of hippocampus, caudate nucleus, putamen, nucleus accumbens and
      amygdala. Lower levels of 5-HT3 receptors were found in other brain regions and
      the cervical vagus nerve. Pharmacological characterization of the labelled 5-HT3
      receptor in human putamen homogenates identified a relatively low affinity for d
      tubocurarine compared to the 5-HT3 receptor in NG108-15 neuroblastoma-glioma cell
      homogenates. In contrast, the affinities of 19 other 5-HT3 receptor ligands were
      not significantly different for the [3H]granisetron-labelled receptor in these
      two preparations. Such findings indicate that the human putamen 5-HT3 receptor
      displays a unique pharmacology which may have significance given the reported
      clinical potential of compounds active at this receptor when assessed in animal
      models of disease.

PMID- 8152524
TI  - Beware the builders: construction noise changes [14C]GABA release and uptake from
      amygdaloid and hippocampal slices in the rat.
AB  - The effects of exposure to chronic noise and vibration, produced by construction
      work, on the release and uptake of [3H]5-hydroxytryptamine ([3H]5-HT) and
      [14C]gamma-aminobutyric acid ([14C]GABA) from rat amygdaloid and hippocampal
      slices were investigated. Noise-exposure resulted in increased release, with no
      significant change in uptake, of [14C]GABA from amygdaloid slices. In hippocampal
      slices, [14C]GABA release was also increased, but the changes in release were
      dependent upon the marked decrease in uptake of [14C]GABA into these slices.
      There was an increase in peak K(+)-evoked release of [3H]5-HT from hippocampal
      slices, but no other changes in [3H]5-HT release or uptake in either region were
      observed following noise-exposure. These findings may have important practical
      implications for the research carried out in laboratories exposed to construction
      noise and vibrations.

PMID- 8152525
TI  - Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate
      receptor antagonism by memantine (1-amino-3,5-dimethyladamantan).
AB  - Memantine (1-amino-3,5-dimethyladamantan) was tested as an antagonist of N-methyl
      D-aspartate (NMDA) receptors on cultured superior collicular and hippocampal
      neurones using the patch clamp technique and its actions were compared to those
      of Mg2+ ions, ketamine, dextrorphan, dextromethorphan, phencyclidine and
      dizocilpine (MK-801). Memantine (2-33 microM) concentration-dependently
      antagonized responses to NMDA 100 microM with an IC50 of 2.92 +/- 0.05 microM. In
      contrast, current responses to (S)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (L-AMPA 50-100 microM) and gamma-amino butyric acid (GABA
      10 microM) were unaffected by Memantine 8 microM. Memantine 8 microM caused a non
      parallel shift of the NMDA concentration-response curve to the right in a manner
      indicative of uncompetitive open channel block. The effects of memantine were
      similar to ketamine in that both antagonists were weakly use- and strongly
      voltage-dependent. In contrast, MK-801, phencyclidine and dextrorphan showed much
      slower kinetics that was reflected in their marked use- and weaker voltage
      dependency. The antagonistic effects of memantine were not reversed by increasing
      concentrations of glycine (0.1-100 microM) ruling out the possibility of an
      interaction of memantine with the strychnine-insensitive glycine modulatory site
      associated with the NMDA receptor-channel complex. Memantine (1-100 microM) also
      selectively antagonized responses to NMDA (40 microM) in the cortical wedge
      preparation with IC50 of 12.9 +/- 1.5 microM.

PMID- 8152526
TI  - Fructose-1,6-bisphosphate fails to ameliorate delayed neuronal death in the CA1
      area after transient forebrain ischaemia in gerbils.
AB  - Fructose-1,6-bisphosphate has been shown to reduce ischaemic-induced brain damage
      in rabbits and gerbils. In view of these findings, we investigated the effects of
      fructose-1,6-bisphosphate on delayed neuronal death, following bilateral
      forebrain ischaemia, in the gerbil hippocampus at the fourth day of reperfusion.
      We subjected gerbils to bilateral forebrain ischaemia for 20 min. Fructose-1,6
      bisphosphate was administered: intraperitoneally at a dose of 1 g/kg in saline in
      hr before the occlusion or at a dose of 1 g/kg 1 hr before the occlusion and
      every 24 hr for 3 days; or intraventricularly at a dose of 0.1 g/kg just after
      the carotid occlusion. No significant differences in the number of dying cells in
      the CA1 area were found between each group of treated animals when compared with
      controls. This study suggests that fructose-1,6-bisphosphate, administered
      according to these three different schedules, fails to ameliorate delayed
      neuronal death after 20 min of bilateral forebrain ischaemia in the CA1 area of
      the gerbil hippocampus.

PMID- 8152527
TI  - Antidepressant treatment and chemical sympathectomy fail to modulate alpha 1
      adrenoceptor sensitivity in mouse eye.
AB  - The mydriatic response to alpha 1-adrenergic agonists was used as a functional
      index of postsynaptic alpha 1-adrenoceptors in mouse iris dilator muscle. Topical
      ocular application of methoxamine or phenylephrine caused dose-related mydriasis
      which was inhibited by pretreatment with prazosin or phentolamine. Chemical
      sympathectomy with topical 6-hydroxydopamine (6-OHDA) produced supersensitivity
      to phenylephrine but not methoxamine. Daily antidepressant treatment for 14 days
      with desipramine (10 mg/kg, i.p.), amitriptyline (10 mg/kg, i.p.), fluoxetine (2
      mg/kg, i.p.), or moclobemide (40 mg/kg, i.p.) did not alter the response to
      methoxamine. Central alpha 1-adrenoceptors labelled with [3H]prazosin were
      similarly unaffected except for a modest downregulation produced by fluoxetine.
      These results demonstrate that postsynaptic alpha 1-adrenoceptors in mouse CNS
      and iris dilator muscle are refractory to manipulations known to alter their
      sensitivity in other tissues.

PMID- 8152528
TI  - Intravenous administration of the serotonin agonist m-chlorophenylpiperazine
      (mCPP) increases extracellular serotonin in the diencephalon of awake rats.
AB  - The serotonin (5-HT) agonist 1-(m-chlorophenyl)piperazine (mCPP) has been widely
      used as a pharmacological probe to assess 5-HT function. Although mCPP is known
      to interact with 5-HT receptors, this drug is also reported to exhibit
      presynaptic actions that increase extraneuronal 5-HT in vitro. In the present
      study, we used in vivo microdialysis to examine the effects of mCPP on
      extracellular 5-HT in the ventromedial diencephalon of awake rats. Intravenous
      mCPP (1.0 and 2.0 mg/kg) increased dialysate 5-HT in a dose-related manner, with
      extracellular 5-HT levels rising 8-fold above baseline after the high dose of
      drug. The stimulatory effect of mCPP on dialysate 5-HT was abolished by
      pretreatment with the 5-HT uptake blocker fluoxetine (10 mg/kg, i.p.). In
      complementary experiments, mCPP elevated plasma prolactin at doses equivalent to
      those that increased dialysate 5-HT, and fluoxetine pretreatment caused a
      partial, though significant, attenuation of mCPP-induced prolactin release. These
      results indicate that mCPP increases extracellular 5-HT in rat brain by a
      presynaptic mechanism involving 5-HT transporters. Moreover, the plasma prolactin
      response to mCPP is at least partially mediated by the presynaptic actions of the
      drug. Our data further suggest the possibility that mCPP exhibits indirect
      agonist properties in human brain. Therefore, clinical studies designed to
      evaluate postsynaptic 5-HT receptor sensitivity based on responsiveness to mCPP
      should be interpreted with caution.

PMID- 8152529
TI  - Role of spinal and supraspinal muscarinic receptors in the expression of morphine
      withdrawal symptoms in the rat.
AB  - Previous studies in this laboratory have demonstrated that prior
      intracerebroventricular (i.c.v.) administration of the muscarinic antagonist, 4
      diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) in morphine dependent rats
      significantly attenuates the development of cardiovascular and certain behavioral
      responses precipitated by the opiate antagonist, naloxone. The purpose of this
      study was to determine whether both supraspinal and spinal cholinergic neurons
      are involved in the expression of withdrawal symptoms. Employing localized
      (i.c.v. or intrathecal, i.t.) infusions of muscarinic antagonists, it was
      determined that a significant antiwithdrawal action could be produced through
      both an inhibition of supraspinal and spinal cholinergic neurons. Pharmacological
      difference emerged regarding the antiwithdrawal potential of 4-DAMP and the
      partially M1 selective antagonist, pirenzepine. While our previous studies had
      revealed that pirenzepine had essentially no antiwithdrawal activity when
      administered by the i.c.v. route, in the present study, pirenzepine evoked a
      marked antiwithdrawal action by the i.t. route, significantly inhibiting both
      cardiovascular and behavioral signs of withdrawal. In contrast, 4-DAMP which was
      effective by the i.c.v. route (especially for the cardiovascular symptoms),
      elicited no antiwithdrawal action by the i.t. route. As a muscarinic antagonist
      (ability to block the pressor response to central injection of carbachol) 4-DAMP
      was equally active by i.c.v. or i.t. injection. However, pirenzepine was clearly
      more effective in this regard by the i.t. route. These results are consistent
      with ability of muscarinic antagonists to offer significant anti-morphine
      withdrawal activity at both supraspinal and spinal locations. They also suggest
      that different muscarinic systems, possibly different receptor subtypes, mediate
      the expression of morphine withdrawal symptoms within the two regions of the CNS.

PMID- 8152530
TI  - The effect of repeated combined treatment with nifedipine and antidepressant
      drugs or electroconvulsive shock on the hippocampal corticosteroid receptors in
      rats.
AB  - The effect of nifedipine, a calcium channel antagonist, on changes in the density
      of glucocorticoid (GR) and/or mineralocorticoid receptors (MR), induced by long
      term treatment with antidepressant drugs (imipramine and amitriptyline) or
      electroconvulsive shock (ECS) was investigated in the rat hippocampus. Long-term
      treatment with imipramine or amitriptyline significantly increased the density of
      GR, while chronic ECS significantly elevated the density of both GR and MR.
      Nifedipine administered repeatedly had no effect on the basal GR and MR levels,
      however when the rats were pretreated with nifedipine, the antidepressant drugs
      and ECS were unable to increase the density of GR, or GR and MR, respectively.
      These results indicate that, unlike in other models, nifedipine blocks the
      effects of antidepressant drugs and ECS on GR and/or MR. They also show, that
      antidepressant drugs and ECS differ in their effect on the density of GR and MR.

PMID- 8152531
TI  - The rostroventromedial medulla is not involved in alpha 2-adrenoceptor-mediated
      antinociception in the rat.
AB  - The aim of the current study was to investigate the role of the
      rostroventromedial medulla (RVM) in alpha 2-adrenoceptor-mediated
      antinociception. Medetomidine or clonidine, selective alpha 2-adrenoceptor
      agonists were microinjected into the RVM in unanesthetized rats with a chronic
      guide cannula. The antinociceptive effects were evaluated using the tail-flick
      and hot-plate tests. For comparison, medetomidine was microinjected into the
      cerebellum or the periaqueductal gray (PAG). To study the role of medullospinal
      pathways, the tail-flick latencies were also measured in spinalized rats. The
      reversal of the antinociception induced by intracerebral microinjections of
      medetomidine was attempted by s.c. atipamezole, a selective alpha 2-adrenoceptor
      antagonist. The reversal of the antinociception induced by systemic
      administration of medetomidine was attempted by microinjections of 5% lidocaine
      or atipamezole into the RVM. When administered into the RVM, medetomidine
      produced a dose-dependent (1-30 micrograms) antinociception in the tail-flick and
      hot-plate tests, which antinociceptive effect was completely reversed by
      atipamezole (1 mg/kg, s.c.). Also clonidine produced a dose-dependent (3-30
      micrograms) antinociception following microinjection into the RVM.
      Microinjections of medetomidine into the cerebellum or the PAG produced an
      identical dose-response curve in the tail-flick test as that obtained following
      microinjection into the RVM. In spinalized rats the antinociceptive effect (tail
      flick test) induced by medetomidine microinjected into the RVM was not less
      effective than in intact rats. Lidocaine (5%) or atipamezole (5 micrograms)
      microinjected into the RVM did not attenuate the antinociception induced by
      systemically administered medetomidine (100 micrograms/kg, s.c.).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8152532
TI  - The quipazine- and TFMPP-increased conditioned avoidance response in rats: role
      of 5HT1C/5-HT2 receptors.
AB  - The role of serotonin (5-HT) in the acquisition of the conditioned avoidance
      response was investigated. The effects of different serotonin agonists and
      antagonists, administered prior to learning sessions, were studied in groups of
      naive rats using the two-way shuttle box. Quipazine, an agonist at 5-HT1B/1C/2
      receptors, significantly increased avoidance responding in a dose-dependent
      manner (1.25-10 mg/kg, s.c.). The putative 5-HT1B/1C receptor agonist TFMPP (1-[m
      trifluoromethylphenyl] piperazine) at doses of 1.25 and 2.5 mg/kg (s.c.),
      increased acquisition of conditioned avoidance but showed no significant
      difference from control at doses of 5 and 10 mg/kg. The 5-HT1A agonist,
      buspirone, significantly decreased acquisition of conditioned avoidance.
      Increased acquisition of conditioned avoidance induced by either quipazine or
      TFMPP was effectively antagonized by the mixed 5-HT 1C/2 receptor antagonists,
      ketanserin (0.2 and 2 mg/kg, s.c.) and mianserin (1 mg/kg, s.c.). In contrast,
      spiperone (5-HT1A/2 receptors antagonist: 0.2 mg/kg, s.c.) only inhibited the
      increased acquisition induced by TFMPP. On the other hand, the 5-HT1A/1B
      receptors antagonist, pindolol, failed to antagonize the increase in acquisition
      of conditioned avoidance caused by quipazine or TFMPP. These results suggest that
      quipazine increases the conditioned avoidance behaviour by an action that might
      be mediated through stimulation of 5-HT1C receptors. The acquisition of
      conditioned avoidance induced by TFMPP, which was blocked by ketanserin,
      mianserin and spiperone but not by pindolol, suggests the involvement of 5-HT1C/2
      receptors in the action of TFMPP.

PMID- 8152533
TI  - Interferon induces sleep and other CNS responses in mice recovering from
      hexobarbital anesthesia.
AB  - Immediately after recovery from hexobarbital anesthesia, mice were injected
      intraperitoneally with one of the following interferons: natural mouse
      alpha/beta, recombinant mouse (rmouse gamma IFN-A) or human alpha A, alpha D,
      alpha AD interferon (rHu alpha IFN-A, rHu alpha IFN-D, rHu alpha IFN-AD). All of
      these interferons, except rHu alpha IFN-A induced unconsciousness ("sleep"); all
      produced stimulatory effects that mimicked those produced by morphine in the
      mouse. Quantification of the duration of sleep, induced by rmouse gamma IFN, was
      investigated and found to be dose-related. Only 3 of the 5 interferons (mouse
      alpha/beta IFN; rmouse gamma IFN, rHu alpha IFN-AD) possesses antiviral activity
      and depresses the cytochrome P-450 system in the mouse, yet all 5 of the
      interferons produced CNS effects. This partition of effects, together with the
      very short latency of the interferon-induced CNS effects, shows that the CNS
      effects were mechanistically independent of the anti-viral and anti-cytochrome P
      450 effects. This disparity of the actions of the interferons suggests the
      possibility that selected morphine antagonists could be used to counter some of
      the dose-limiting CNS effects of the large doses of interferons used in clinical
      situations.

PMID- 8152534
TI  - Antagonism of baclofen-induced depression of whole-cell synaptic currents in
      spinal dorsal horn neurones by the potent GABAB antagonist CGP55845.
AB  - The potencies of two GABAB receptor antagonists P-[3-aminopropyl]- P
      diethoxymethyl-phosphinic acid (CGP35348) and the novel compound 3-N[1-(S)-(3,4
      dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P- benzyl-phosphinic acid
      (CGP55845) have been compared in an in vitro spinal cord preparation. They have
      been tested as antagonists of baclofen-induced depression of EPSCs of patch
      clamped dorsal horn neurons following electrical stimulation of dorsal roots.
      Mean EC50 values for the depressant action of baclofen were increased by 50- and
      140-fold respectively in the presence of CGP35348 (200 microM) (n = 5) and
      CGP55845 (100 nM) (n = 4). This potency of CGP55845 is > 1000-fold higher than
      that reported previously for other GABAB receptor antagonists.

PMID- 8152535
TI  - Assessment of brain muscarinic acetylcholinergic receptors in living mice using a
      simple probe, [125I]-4-iododexetimide and [125I]-4-iodolevetimide.
AB  - This study describes assessment of brain muscarinic acetylcholinergic receptors
      in living mice using a single-crystal radiation detection system, the high
      affinity antagonist [125I]-4-iododexetimide, and the inactive enantiomer [125I]-4
      iodolevetimide. Kinetics of radioligand binding, as well as perturbation by
      atropine displacement, can be determined using this simple probe technique.

PMID- 8152536
TI  - Possible functional role of diadenosine polyphosphates: negative feedback for
      excitation in hippocampus.
AB  - Diadenosine polyphosphates (Ap4A and Ap5A) are present in secretory granules of
      chromaffin cells as well as in the rat brain synaptic terminals. Their
      contribution to the exocytosis of the total synaptosomal content is considerable,
      ranging from 7% to 12%. Ap4A and Ap5A are released from synaptosomes in a Ca(2+)
      dependent manner. There are indications on the high affinity of diadenosine
      polyphosphates to P2 receptors, but their action on P1 receptors remains unclear.
      Here we report that both substances induce a blocking action on excitatory
      synaptic transmission in the rat hippocampus. This action is elicited via the A1
      (subclass of P1) receptors and differs in some respects from the action of
      adenosine.

PMID- 8152537
TI  - Status epilepticus may be caused by loss of adenosine anticonvulsant mechanisms.
AB  - The inhibitory neuromodulator adenosine is an endogenous anticonvulsant that
      terminates brief seizures in the brain and it has been proposed that loss of
      adenosine or adenosine-mediating systems may play a major role in the development
      of status epilepticus, a seizure condition characterized by prolonged and/or
      recurrent seizures that last by definition, at least 20 min. In this study, the
      effect of specific A1-adenosine agonists and antagonists were tested for their
      ability to prevent and cause status epilepticus in two electrical stimulation
      models in rats. In a recurrent electrical stimulation model, whereas no vehicle
      treated animals developed status epilepticus after 20 recurrent electrical
      stimulations, rats injected with 10 mg/kg of the specific A1-adenosine antagonist
      8-cyclopentyl-1,3-dimethylxanthine intraperitoneally developed status epilepticus
      after stimulation. 8-(p-Sulphophenyl)-theophylline, which has limited
      penetrability into the brain when administered peripherally, did not cause status
      epilepticus when injected intraperitoneally. However, when 200 micrograms of 8-(p
      sulphophenyl)-theophylline were administered intracerebroventricularly, status
      epilepticus developed in all animals, suggesting status epilepticus developed as
      a result of central adenosine receptor antagonism. In the second study, whereas
      all vehicle-treated animals developed status epilepticus after constant
      electrical stimulation, administration of N6-cyclohexyladenosine and N6
      cyclopentyladenosine prior to stimulation suppressed the development of status
      epilepticus. N6-Cyclohexyladenosine was also effective in terminating status
      epilepticus after it had progressed for 20 min. The effects of a selective A2
      agonist was also tested on both stimulation models and had no anticonvulsant
      effects. An electrical stimulus given to rats pretreated three days prior to
      stimulation with pertussis toxin, a compound which inactivates Gi-proteins, also
      resulted in generalized status epilepticus, suggesting that impairment of G
      protein-linked receptors is involved in the development of status epilepticus.
      The effects of a GABAB antagonist, phaclofen, and a GABAB agonist, baclofen, were
      also tested in the recurrent stimulation model, as GABAB receptors are also
      coupled to the same subset of K+ channels as the A1-receptor. Rats given
      phaclofen did not develop status epilepticus after recurrent electrical
      stimulation, although baclofen was effective at preventing the induction of
      status epilepticus in the constant stimulation model. These results, together
      with some preliminary data obtained showing that the GABAA antagonist picrotoxin
      did not cause status epilepticus after recurrent stimulation, suggest that loss
      of GABAergic inhibition only has a minor role in status epilepticus development
      in our models. Brains from all animals were also assessed for brain
      injury.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8152538
TI  - Staurosporine impairs both short-term and long-term potentiation in the dentate
      gyrus in vitro.
AB  - The present study shows that the protein kinase inhibitor staurosporine impairs
      the transient (< 60 min) potentiation (short-term potentiation) evoked by a weak
      tetanus to about the same extent as the more stable potentiation (long-term
      potentiation) evoked by a strong tetanus. This effect on short-term and long-term
      potentiation was seen both as a reduced magnitude and an increased decay rate,
      the latter being increased by about 50% compared to that seen under normal
      conditions. Comparison with potentiations evoked at different strengths in
      control solution suggested that much, but not all, of the increased decay rate
      observed in the presence of staurosporine could be explained by an impared
      induction. Staurosporine did not affect the N-methyl-D-aspartate-mediated field
      excitatory postsynaptic potential evoked by low-frequency stimulation or the
      magnitude of N-methyl-D-aspartate-mediated currents during high-frequency
      tetanization. This result suggests that the induction is impaired at a stage not
      related to the N-methyl-D-aspartate-mediated calcium influx. The present results
      suggest that short-term and long-term potentiation cannot be separated on the
      basis of protein kinase dependence. They do not support the common notion that
      short-term and long-term potentiation are mechanistically separate entities.
      Instead, the results support the view that long-term potentiation has a variable
      duration/stability dependent on the induction conditions and that protein kinase
      activation, via an action on induction mechanisms, contributes to its
      stabilization.

PMID- 8152539
TI  - Walking evokes a distinctive pattern of Fos-like immunoreactivity in the caudal
      brainstem and spinal cord of the rat.
AB  - We have evaluated the pattern of c-fos expression induced in the rat spinal cord,
      caudal brainstem and cerebellum by a behavior that is associated with non-noxious
      inputs transmitted over large-diameter primary afferent fibers, namely walking
      for 1 h on a rotating rod. Walking on the rotating rod induced a large increase
      in the number of Fos-like immunoreactive neurons in regions of the cervical and
      lumbar spinal cord gray matter that contain neurons that respond to non-noxious
      stimuli: the inner part of the substantia gelatinosa (lamina IIi), the nucleus
      proprius and the medial parts of laminae V and VI. We also observed considerable
      labeling in lamina VII and in ventral horn motoneurons. We did not record an
      increased number of Fos-like immunoreactive neurons in lamina I, in the outer
      substantia gelatinosa (lamina IIo), or in the lateral, reticulated portion of
      lamina V, regions that contain neurons predominantly responsive to noxious
      stimulation. Unilateral sensory deafferentation of the forelimb, by multiple
      dorsal rhizotomies, significantly decreased the number of Fos-like immunoreactive
      neurons in the ipsilateral spinal cord, suggesting that afferent input
      contributed to the walking-induced pattern of labeling. In rats that walked on
      the Rota-Rod, we also recorded increased labeling in the dorsal column nuclei.
      Unilateral cervical deafferentation reduced the labeling in the cuneate nucleus;
      this reduction was paralleled by decreased cytochrome oxidase activity. Finally,
      we found that there was a significant increase in the number of Fos-like
      immunoreactive neurons in the cerebellum of rats that walked on the Rota-Rod.
      Northern blot analysis revealed that the increase in Fos-like immunoreactivity
      was associated with an increase in c-fos messenger RNA. The pattern of labeling
      observed in the rats that walked on the Rota-Rod was distinct from that observed
      when rats are exposed to a noxious stimulus [Presley et al. (1990) J. Neurosci.
      10, 323-335]. This result reinforces the conclusion that by monitoring the evoked
      expression of the c-fos proto-oncogene, it is possible to identify unique
      populations of neurons that are specifically related to the modality of the
      stimulus or to behaviour occurring during the stimulus presentation.

PMID- 8152540
TI  - Hindbrain structures involved in pain processing as revealed by the expression of
      c-Fos and other immediate early gene proteins.
AB  - We have used the evoked expression of the immediate early gene-encoded proteins
      (c-Fos, Fos B, Jun B, Jun D, c-Jun and Krox-24) to monitor sensory processing in
      the hindbrain structures of rats undergoing somatic inflammation. Experiments
      were performed on freely moving animals that did not experience constraints other
      than those imposed by the disease itself. Local injections of chemicals were used
      to cause subcutaneous inflammation of the plantar foot or monoarthritis by
      intracapsular injection. Labelling was studied at survival times that
      corresponded either to the time points of maximum labelling in the spinal cord (4
      h for the subcutaneous model, 24 h and two weeks for the monoarthritis model) or
      at survival times that corresponded to the chronic phase of monoarthritis
      evolution (six, nine and 15 weeks). Controls consisted of freely moving,
      unstimulated animals. Basal expression was observed for all immediate early genes
      and in a variety of structures, but always remained moderate. All immediate early
      gene-encoded protein expressions except c-Jun were evoked, but except for c-Fos,
      and to a lesser extent Jun D, intensities of staining always remained faint. The
      following results will be mainly based on c-Fos expression, as this protein
      proved to be the most effective marker for all the survival times studied.
      Somatic pain evoked c-Fos expression in a subset of discrete subregions of both
      the caudal medulla oblongata and transitional areas of the pontomesencephalic
      junction. In the caudal medulla oblongata, structures involved were the caudal
      intermediate reticular nucleus, the subnucleus reticularis dorsalis, the
      ventrolateral reticular formation and the lateral paragigantocellular nucleus.
      Structures involved at the pontomesencephalic junction level mostly included the
      superior and dorsal lateral subnuclei of the parabrachial area, the nucleus
      cuneiformis and the most caudal portions of the lateral central gray, also
      including the laterodorsal tegmental nucleus; labelling in other lateral
      subnuclei of the parabrachial area always remained moderate. Staining in the
      caudal reticular areas was evident only at short survival times (4 and 24 h
      survival times in subcutaneous and monoarthritis models, respectively). Staining
      in nuclei of the pontomesencephalic junction was evident in all cases except for
      the very long survival periods (six to 15 weeks) of monoarthritis. In all cases
      staining was bilateral with contralateral predominance with regard to the
      stimulated limb. The present work demonstrates that hindbrain structures involved
      in somatic pain processing can be effectively identified in behaving animals and
      that c-Fos is the most reliable activity marker in this case.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8152541
TI  - Effects of descending inhibitory systems on the c-Fos expression in the rat
      spinal cord during formalin-induced noxious stimulation.
AB  - This study provides morphological evidence for the activation of the descending
      modulatory control by nociceptive afferent pathways. Fos-like immunoreactivity in
      the spinal dorsal horn is used as an indicator of efficacy of transmission of
      noxious inputs at this level. Wistar rats were anesthetized with nembutal and the
      spinal dorsolateral funiculus was transected unilaterally at the level of T11,12.
      Two days later, an equal volume (0.2 ml) of formalin (5% in saline) was injected
      into the plantar aspect of two hindpaws. After 1 h of injection, rats were deeply
      anesthetized and killed for the immunocytochemical examination of Fos-like
      protein product by using an immunocytochemical technique. The results show that
      the mean number of Fos protein-like immunoreactive neurons is significantly lower
      in the superficial laminae and in the neck of the dorsal horn on the side
      ipsilateral to the intact dorsolateral funiculus than that on the opposite side
      (i.e. 18.4 +/- 1.0 vs 30.0 +/- 1.3 and 33.9 +/- 0.2 vs 56.8 +/- 1.7,
      respectively). We conclude that the peripheral noxious inputs (which ascend via
      the ventral half of the spinal cord in this study) can activate the supraspinal
      descending inhibitory systems, which in turn suppress the synthesis of Fos-like
      protein in the related dorsal horn neurons.

PMID- 8152542
TI  - Application of morphine prior to noxious stimulation differentially modulates
      expression of Fos, Jun and Krox-24 proteins in rat spinal cord neurons.
AB  - The expression of Fos, Jun and Krox-24 proteins was investigated in spinal cord
      neurons of the rat 2, 4 and 8 h following noxious thermal stimulation of one hind
      paw and pre-treatment with morphine. The number of neurons expressing c-Fos, c
      Jun, Jun B and Krox-24 were maximal after 2 h and thereafter declined. The number
      of Fos B and Jun D immunoreactive neurons increased constantly for up to 8 h with
      Jun D showing expression above baseline only after 4 h following stimulation.
      Intravenous application of morphine (5 and 10 mg/kg) 20 min before noxious heat
      stimulation decreased the expression of all six proteins at any time-point with a
      predilective effect on neurons of deeper laminae of the dorsal horn. The
      suppressive effects of morphine were more pronounced with the higher dose of
      morphine and completely reversed by intravenous naloxone (1 and 10 mg/kg). The
      temporospatial patterns of expression following morphine were similar to those
      seen without morphine, but in a much smaller number of neurons and with a shorter
      time-course. However, despite the high dose of morphine and continuous halothane
      anaesthesia during the whole experimental procedures, a considerable number of
      neurons expressing the various genes remained in all laminae of the spinal cord.
      At 2 h following noxious heat stimulation morphine had decreased the number of
      labelled neurons for c-Fos, Fos B, Krox-24, c-Jun and Jun B to 30-60% of control
      levels in laminae I-II and to 10-30% in laminae III-VII,X of the spinal cord. At
      4 h the level of reduction had further increased while Jun D was only moderately
      reduced to 75% in all laminae of the spinal cord. Eight hours following noxious
      heat plus morphine application we did not detect noxious evoked immunoreactivity
      for c-Fos, Krox-24, c-Jun and Jun B, while there was residual labelling for Fos B
      in the superficial dorsal horn and for Jun D in laminae I-VII and X of the spinal
      cord. The different temporospatial pattern of immediate early gene expression in
      neurons of the spinal cord dorsal horn following noxious stimulation suggest that
      variable transcription complexes may interact with DNA regulatory sequences and
      could thus activate alternative secondary response genes, even under protection
      of a high dosage of morphine applied before noxious stimulation.

PMID- 8152543
TI  - Role of neurotrophins in the control of neural development: neurotrophin-3
      promotes both neuron differentiation and survival of cultured chick retinal
      cells.
AB  - The effects of neurotrophins brain-derived neurotrophic factor and neurotrophin-3
      on cultured dissociated cells from chick retina were studied at several embryonic
      ages from day 4 to day 13. Precursor cells from days 4-7 retinas proliferated in
      vitro and, after 20 h in culture, a proportion of them underwent spontaneous
      differentiation, as judged by both [3H]thymidine uptake and acquisition of
      neuronal morphology and neuron-specific markers. Brain-derived neurotrophic
      factor did not affect neuronal differentiation, although this factor supports
      survival of differentiated retinal ganglion cells [Rodriguez-Tebar et al. (1989)
      Devl Biol. 136, 296-303]. However, in cultures from young undifferentiated
      retinas, neurotrophin-3 produced up to a 2.5-fold increase in the number of
      [3H]thymidine-positive neurons, i.e. those that in vitro replicated their DNA.
      Moreover, in older retinas, neurotrophin-3, like brain-derived neurotrophic
      factor, supported the survival of differentiated retinal ganglion cells over a
      short developmental period. This effect was negligible at embryonic day 5,
      maximal at day 9, decreased at day 11 and was absent at embryonic day 13.
      Neurotrophin-3 also supported the survival of a population of amacrine neurons.
      This effect was modest at embryonic day 9, and increased at days 11 and 13. Our
      results show that, whereas the action of brain-derived neurotrophic factor is
      restricted to differentiated neurons, neurotrophin-3 exerts two distinct
      successive actions on retinal cells in vitro: first, this factor promotes either
      differentiation of neuroepithelial cells or maturation of recently differentiated
      neurons, and later in development, this factor supports the survival of
      differentiated retinal ganglion and amacrine cells but only during a discrete
      post-differentiation period.

PMID- 8152544
TI  - Reduction of voluntary alcohol intake in the rat by modulation of the
      dopaminergic mesolimbic system: transplantation of ventral mesencephalic cell
      suspensions.
AB  - The dopaminergic mesolimbic system plays a major role in the mechanisms of reward
      and positive reinforcement, and is also known to be a primary target for the
      action of substances that are self-administered and are considered drugs of
      abuse. Even though alcohol administration has been shown, by physiological and
      pharmacological manipulations, to cause changes in the mesolimbic dopaminergic
      system, it has not yet been determined whether, conversely, experimentally
      induced changes in this system are effective in regulating the voluntary intake
      of ethanol. In the present study we assessed the effects of the intrastriatal
      transplantation of fetal dopaminergic grafts on the regulation of voluntary
      alcohol intake in the rat. Fetal dopaminergic transplants from ventral
      mesencephalon--but not dopamine-poor transplants or sham-operated animals-
      reduced the voluntary intake of ethanol by about 40-50%. These results indicate
      that the effects obtained are due to the dopaminergic nature of the grafts, and
      not the consequence of a non-specific effect of the graft, or of the surgical
      procedure itself. These results support the hypothesis that the dopaminergic
      mesolimbic system plays an important role in the regulation of the voluntary
      intake of ethanol.

PMID- 8152545
TI  - Topographic organization of collateral projections from the basolateral
      amygdaloid nucleus to both the prefrontal cortex and nucleus accumbens in the
      rat.
AB  - The basolateral amygdaloid nucleus, a limbic/autonomic center in the basal
      forebrain, has been known to send projection fibers to the prelimbic and dorsal
      agranular insular areas in the prefrontal cortex, as well as to the nucleus
      accumbens. In the present study, we investigated single basolateral amygdaloid
      nucleus neurons sending their axons to both the prefrontal cortex and nucleus
      accumbens. The fluorescent retrograde double-labeling technique was employed in
      the rat; True Blue was injected into the prelimbic or dorsal agranular insular
      cortex, and Diamidino Yellow into the medial or lateral part of the nucleus
      accumbens. The majority of basolateral amygdaloid nucleus neurons projecting to
      the dorsal agranular insular cortex or prelimbic cortex were located,
      respectively, in the rostral two-thirds or caudal two-thirds of the nucleus,
      while those projecting to the medial or lateral part of the nucleus accumbens
      were diffusely distributed in the nucleus. Almost 50% of basolateral amygdaloid
      nucleus neurons projecting to the prelimbic cortex sent their axon collaterals to
      the medial part of the nucleus accumbens. About 30-40% of basolateral amygdaloid
      nucleus neurons projecting to the dorsal agranular insular cortex or prelimbic
      cortex issued their axon collaterals to the lateral part of the nucleus
      accumbens. The axons bifurcating to both the dorsal agranular insular cortex and
      lateral part of the nucleus accumbens, those bifurcating to both the prelimbic
      cortex and lateral part of the nucleus accumbens, or those bifurcating to both
      the prelimbic cortex and medial part of the nucleus accumbens arose
      preferentially from the rostral, middle or caudal parts of the basolateral
      amygdaloid nucleus, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152546
TI  - Ganglion cell neurogenesis, migration and early differentiation in the chick
      retina.
AB  - Neurogenesis, migration and maturation of ganglion cells in the posterior pole of
      chick retina have been studied using embryonic incorporation of [3H]thymidine,
      immunocytochemistry and retrograde labeling. Unlike previous studies, we have
      examined the neurogenesis of independently identified ganglion cells that have
      survived the period of naturally occurring cell death (embryonic days 11-16).
      Embryos were labeled with [3H]thymidine at different embryonic ages (embryonic
      days 3, 5 and 7). After the chicks hatched, ganglion cells were retrogradely
      labeled with rhodamine microspheres and the retinas were processed for
      autoradiography and fluorescent microscopy. The results indicate that 40% of the
      ganglion cells in the posterior pole undergo a final mitosis by embryonic day 3
      and that more than 25% of the ganglion cells are born on or after embryonic day
      7. These results also suggest that naturally occurring cell death does not
      preferentially affect ganglion cells born on specific embryonic days. Using
      immunocytochemistry with an antibody against neuron-specific beta-tubulin and
      retrograde labeling with the carbocyanine dye DiI we show that ganglion cells
      begin to differentiate before the completion of their migration to the
      presumptive ganglion cell layer. These results suggest the following
      developmental sequence. (1) Ganglion cells of the posterior pole undergo their
      final mitosis near the ventricular margin between embryonic days 2 and 8. (2)
      They maintain contacts with both retinal surfaces and their nuclei move toward
      the ganglion cell layer. At this time they start to differentiate, expressing a
      form of neuron-specific tubulin and growing axons that can reach the optic
      chiasm. (3) Once migration is completed dendritic development commences.

PMID- 8152547
TI  - Regeneration of rat sciatic nerves in silicone tubes: characterization of the
      response to low intensity d.c. stimulation.
AB  - Endogenous d.c. electric fields have been postulated to play a role in normal
      development and repair functions of a variety of living systems. The corollary
      hypothesis, that exogenous electric fields can alter development and repair
      mechanisms, has led to the use of d.c. electric fields as a means to enhance
      mammalian peripheral nerve regeneration. This study investigates the response of
      transected rat sciatic nerves within silicone tubes to low intensity d.c.
      stimulation. In 40 rats, the right sciatic nerves were transected and sutured
      into silicone tubes, leaving a 5.0 mm gap between the stumps. The nerves were
      either treated with 10 microA d.c., with the cathode at the midpoint of the tube
      and the anode distant, or received no exogenous current. Three weeks later,
      transverse sections from the center of the tissue bridging the two segments were
      analysed by sampling approximately 12% of the cross sectional area, using x 1000
      magnification on the light microscope. All non-stimulated (control) nerves showed
      regeneration of myelinated axons at the center of the bridge, while only 35% of
      the nerves stimulated with 10 microA had such a response. Of the nerves with
      regeneration of myelinated axons at the center of the tube, the control nerves
      had significantly more myelinated axons (P = 0.0028) than treated nerves.
      Stimulated nerves showed bizarre regeneration responses, including formation of
      multiloculated cysts and neuroma-like formations. In control nerves there was a
      gradual tapering of axon number from proximal to distal in the regeneration
      bridge, while in the stimulated nerves there was a sharp decrease in the number
      of axons proximal to the cathode. We hypothesize that this effect is due to the
      accumulation of electrolysis products at the cathode, which inhibit regeneration
      through this region. Regeneration of transected rat sciatic nerves is not
      enhanced by electric currents applied in this manner. Previous work interpreted
      the increased number of axonal cross-sections in the tube as an increase in the
      absolute number of regenerating fibers. Our data suggest that the increased
      number of axonal cross-sections is due to neuroma formation, probably in response
      to the accumulation of electrolysis products at the cathode. This work brings
      into question claims of an enhancement of peripheral nerve regeneration by
      applied electric fields.

PMID- 8152549
TI  - 44th Annual meeting of the American Academy of Neurology. Washington, D.C., May 1
      7, 1994. Abstracts.

PMID- 8152548
TI  - Exploring the functional domain and the target of the tetanus toxin light chain
      in neurohypophysial terminals.
AB  - The tetanus toxin light chain blocks calcium induced vasopressin release from
      neurohypophysial nerve terminals. Here we show that histidine residue 233 within
      the putative zinc binding motif of the tetanus toxin light chain is essential for
      the inhibition of exocytosis, in the rat. The zinc chelating agent dipicolinic
      acid as well as captopril, an inhibitor of zinc-dependent peptidases, counteract
      the effect of the neurotoxin. Synthetic peptides, the sequences of which
      correspond to motifs present in the cytoplasmic domain of the synaptic vesicle
      membrane protein synaptobrevin 1 and 2, prevent the effect of the tetanus toxin
      light chain. Our results indicate that zinc bound to the zinc binding motif
      constitutes the active site of the tetanus toxin light chain. Moreover they
      suggest that cleavage of synaptobrevin by the neurotoxin causes the inhibition of
      exocytotic release of vasopressin from secretory granules.

PMID- 8152550
TI  - [Video-laparoscopic Nissen-Rossetti fundoplication].
AB  - The authors describe the application of Nissen-Rossetti fundoplication for the
      treatment of hiatus hernia using a laparoscopic approach. They report excellent
      results both immediately after surgery and in the medium term.

PMID- 8152551
TI  - [Repair of splenic lesions with video-laparoscopy].
AB  - Conservative therapy of spleen injuries (non-operative treatment, partial
      splenectomy, autotransplantation, etc.) makes it possible to avoid the risk
      related to post-splenectomy hyposplenism. The videolaparoscopic approach makes
      the performance of such treatment possible achieving a clear reduction in
      surgical stress. The authors report two multiple injured patients showing spleen
      lesions, treated conservatively through videocoelioscopic procedure. Both
      patients (a 42-year-old woman and a 26-year-old man) presented hemorrhagic shock
      in hemodynamic compensation and hemoperitoneum. Abdominal ultrasonographic
      scanning proved the presence of spleen injuries. Both patients underwent a
      conservative surgical videolaparoscopic treatment using fibrin glue and
      omentoplasty. The resolution of the hemorrhagic shock and the restoration of the
      spleen lesions were achieved in both cases. The authors have already used the
      videocoelioparoscopic approach both in elective (biliary lithiasis, inguinal
      hernia, appendicitis, etc.) and in emergency surgery (acute cholecistitis,
      perforated ulcer, intestinal obstruction, etc.). They note the effectiveness of
      the method, also in the field of the mini-invasive conservative treatment of
      parenchymatous organ lesions (mainly in the case of spleen injuries, when the
      splenic function has to be preserved). So, it's possible to add the advantages of
      a conservative treatment to those of the minimal invasivity, provided by the
      videolaparoscopic procedure.

PMID- 8152552
TI  - [Update on laparoscopic surgery: on the treatment of hydatid cyst of the liver
      and peritonitis caused by a perforated duodenal ulcer].
AB  - Laparoscopic surgery represents a real innovation with respect to the traditional
      laparotomic way of access, owing to its undeniable advantages, both
      intraoperative and postoperative. This new technique reduces the complications
      connected with the surgical wound and with forced allerement. Therefore it allows
      the patient's fast recovery. Laparoscopic surgery application ground get's wider
      and wider every day: in fact, the authors report two medical cases, one of
      elective surgery (treatment of a hidatid cyst of the liver) and the other in
      emergency surgery (peritonitis due to perforated duodenal ulcer), both obtaining
      a positive result about the clinical and the postoperative timing of recovery.

PMID- 8152553
TI  - [Diagnostic and therapeutic update on primary duodenogastric reflux].
AB  - The authors, after some remarks on the pathophysiology of primary alkaline
      gastritis, analyze the main methods, available at present, for diagnosis; they
      particularly consider the importance of endoscopy and histology, gastroesophageal
      24-hours pH-metry and 99mTc HIDA scintigraphy. Successively, they present the
      criteria for the identification of patients who will predictably benefit from
      surgical treatment, and examine advantages and limits of the two main corrective
      surgical techniques for the duodenogastric reflux in patients not previously
      operated on the gastrointestinal tract: duodenal extramucosal myotomy according
      to Mattioli, relatively easy to perform, and the "duodenal switch" according to
      De Meester, technically more complex, but pathophysiologically more acceptable,
      completely eliminating the duodenogastric reflux.

PMID- 8152554
TI  - [The treatment of benign lesions of the liver. Indications and surgical
      approach].
AB  - Benign formations in the liver constitute a heterogeneous group of pathology
      lesions that are rarely found clinically. In the period between January 1985 and
      June 1992, 81 patients, affected by benign formations of the liver, were observed
      at the Institute of the III Surgical Clinic of Rome "La Sapienza". Most of these
      lesions are asymptomatic and their diagnosis is mostly casual. Among these we
      found 48 cases of echinococcus cystis, 13 cases of congenital cystic formations,
      2 amoebiasis cases, and 1 case the ecografic exam, which shows an hepatic
      formation to the fifth segment, was not in conformity with the cytologic exam
      which proved negative because of cellular abnormalities of any nature, therefore
      it's constituted by normal parenchyma. Consequently the patient was discharged.
      We operated on 65 patients. The complications found in the patient operated on
      were not important and we had the death of only 1 patient affected by hepatic
      abscess on the 3rd day after surgery because of septicemia and cardio-circulatory
      problems. The follow-up made after a certain time has resulted negative because
      of relapses if we exclude 1 case of echinococcus cystis wherein we found a
      serological relapsing. In our experience and according to most of the authors,
      the operation must take place always in cases such as: adenoma, cystoadenoma,
      hemangiomas having a diameter higher than 3 cm, echinococcus cysts, syntomatic
      formations and when we have complications. For all other cases we must limit
      ourselves to observation over a certain period both the dimensions and
      morphological modification of the lesions.

PMID- 8152555
TI  - [Microcystic serous cystadenoma of the pancreas. Enucleation or regulated
      pancreatic resection?].
AB  - Cystic benign tumors of the pancreas are rare lesions: they represent less than
      10% of all pancreatic neoplasms. We studied two cases of microcystic adenoma, one
      of the less common varieties, that only in the last few years has been
      morphologically recognized as a distinct pathological entity. Our clinical
      experience--though limited--made us remark some interesting features: 1)
      preoperative diagnostic procedures (ultrasonography and CT) may present great
      interpretative difficulties: in one of the cases observed, radiographic imaging
      demonstrated an unresectable pancreatic tumor. On the contrary, in both cases
      surgical radicality has been achieved; 2) preoperative needle aspiration cytology
      (FNAB) does not always provide diagnostic material, as happened in both case
      observed; 3) the diagnosis of a benign tumor may result from surgical exploration
      and multiple biopsies with intraoperative frozen sections. Further and more
      complex histological investigations will definitively diagnose a microcystic
      adenoma; 4) in disagreement with some authors' results, we observed that
      microcystic adenoma may grow rapidly: one of our patients, after an incomplete
      tumor enucleation, developed a local relapse in a few months, needing a subtotal
      distal pancreatectomy, followed by complete recovery; 5) surgical radicality is
      mandatory. This result can be achieved through a simple, but complete, tumor
      enucleation or through a pancreatic resection; 6) our immunohistochemical and
      ultrastructural studies on microcystic adenoma exhibited no cells with endocrine
      activity, supporting the hypothesis that this tumor may originate from ductal or
      centroacinar cells.

PMID- 8152556
TI  - [Obstruction of the Le Veen shunt: a new surgical solution].
AB  - The authors propose an alternative which has been proved valid in four cases of
      peritoneovenous shunt with an occluded Le Veen valve for venous thrombosis
      implanted in cirrhotic patients with refractory ascites. After having explored
      the various possibilities using the vessels adjacent to the superior cava branch,
      the authors resolved the problem of reimplanting the valve by using an access
      route through the saphenous vein and inferior vena cava. Using this technique it
      was possible to reactivate the shunt with a marked improvement in the recurrent
      ascitic state and above all shunt functionality, and consequently in the clinical
      conditions and quality of life of these patients.

PMID- 8152557
TI  - [Preoperative diagnosis of thyroid nodule. Ultrasonography-guided fine-needle
      aspiration].
AB  - Nodular thyroid pathology weighs heavily for 4-5% of the general population,
      being the most common among the endocrinopathies. Because of this these
      diagnostic methods have gained more and more importance as FNA able to select
      already in the pre-operation phase the malignant nodules from the benign ones and
      to decide on the most suitable surgical intervention. In the period of time
      between January 1989 and June 1992 in the Institute of the III Surgical Clinic in
      Rome there have been performed 403 FNA. From the whole total we have extrapolated
      221 patients. In this study we stressed how the FNA method has a sensibility of
      80%, a specificity of 93% and afterwards an accurate diagnosis of 92%. Besides we
      have verified that sonography and radionuclide scanning have a truth worthiness
      respectively of 64% and 52%. The FNA in our opinion allows us to have in the pre
      operation phase a much more accurate diagnosis as regards that obtained with only
      sonography and radionuclide scanning therefore the latter methods must be
      considered complementary to FNA.

PMID- 8152558
TI  - [Lymphocytic infiltration in thyroid neoplasms. Preliminary prognostic
      assessments].
AB  - INTRODUCTION: It is known that the immune system is involved in several thyroid
      diseases and in the reaction against cancer progression. We have therefore
      evaluated lymphocytic infiltration in the slices of surgically removed thyroids
      in patients affected by thyroid carcinomas, to further clarify the anatomic and
      clinical characteristics of this pathology and the possible prognostic
      correlations. MATERIALS AND METHODS: Thirty-eight patients, 7 men and 31 women,
      aged 23-73 years, were studied. They underwent total or subtotal thyroidectomy
      for thyroid carcinoma. The histopathological findings were: papillary carcinomas
      (P): 22 cases; follicular carcinomas (F): 10 cases; undifferentiated carcinomas
      (U): 3 cases; other types (e.g., medullary carcinoma, M): 3 cases. RESULTS: The
      lymphocytic infiltration was evaluated in 4 different grades. The following
      results, regarding the different histological types, were found: grade 0 (no
      lymphocytic infiltration) in 10 cases (6 P, 2 F, 1 U, 1 mixed); grade 1 (poor
      lymphocytic infiltration, equivalent to a non specific inflammatory reaction) in
      21 cases (11 P, 6 F, 2 U, 1 M); grade 2 (moderate lymphocytic infiltration) in 4
      cases (2 P, 2 F); grade 3 (plentiful lymphocytic infiltration) in 3 cases (2 P, 1
      trabecular carcinoma). In 3 patients a lymphocytic (Hashimoto's) thyroiditis was
      also present. The follow-up, 2 years after surgery, showed, among 17 patients
      examined, local recurrence and/or lymph node localization in 8 cases (the
      lymphocytic infiltrations was: grade 1: n = 6; grade 0: n = 2; no one exhibited a
      higher grade) and apparent remission in 9 (grade 3: n = 2; grade 2: n = 1; grade
      1: n = 6; no one exhibited a grade 0 lymphocytic infiltration). DISCUSSION: In
      most patients a poor or absent infiltration was found. In 7 cases, however, the
      infiltration was moderate or high. In our experience, no correlation between the
      histologic type and the infiltration grade was observed. However, in no patient
      with recurrence of neoplasia a relevant (grade 2-3) infiltration could be
      observed; patients without recurrence often showed a grade 2-3 infiltration, and
      no one of them showed a grade 0. The significance of lymphocytic infiltration in
      thyroid carcinoma is not well clarified. In fact, a few studies underline a
      possible unfavourable role, since a relevant infiltration seems to be associated
      with a weak cell-mediated immunity, mostly in follicular and anaplastic
      carcinomas. However, most data support the hypothesis that the lymphocytic
      infiltration is a good prognostic feature: in fact, it can be often found in
      papillary carcinomas and in juvenile thyroid carcinomas, both characterized by a
      good long-term prognosis. CONCLUSIONS: Our preliminary data underline the
      opportunity of comparing the clinical course of the disease, the histologic
      grading and the tumour staging with the lymphocytic infiltration grade, an easily
      available pathologic datum, for a better prognostic evaluation of patients.

PMID- 8152559
TI  - [Medullary thyroid carcinoma: prognostic factors].
AB  - Fifty-one patients treated by total thyroidectomy plus nodal neck dissection of
      necessity for medullary thyroid carcinoma (MTC) with a minimum follow-up of 10
      years (mean 14.5, max 22 years) were divided into three groups according to the
      outcome (alive disease-free; alive with disease; dead) and were compared in order
      to analyze the prognostic factors of MTC. Twenty years actuarial survival rate
      for age at diagnosis less than 50 years versus age over 50 (90% vs 45%) as well
      as for stage II versus stage III (85% vs 55%) was statistically different (p <
      0.005 and p < 0.05 respectively). About 60% of recurrences were observed within 5
      years after surgical treatment. Recurrence rate for stage III (70%) versus stage
      II (20%) was statistically different, but it was not for the age. Survival rate
      for patients with bony metastases (50% at 1 and 30% at 3 years) versus patients
      with other than bony metastases (100% at 10 years) was statistically different.

PMID- 8152560
TI  - [Anaplastic carcinoma of the thyroid: long-term survival].
AB  - Anaplastic carcinoma of the thyroid is a highly aggressive neoplasm with quickly
      total course. It is characterized by an average survival of 4-12 months. It
      infiltrates precociously into the windpipe, oesophagus, vessels of the neck and
      gives distant metastases in 10-48% of cases. In 30.8 to 80% of cases, this
      carcinoma originates in an old multinodular goiter. The hypothesis has been also
      advanced that this neoplasm could derive from a pre-existent well-differentiated
      carcinoma. The improvement in diagnostic techniques (especially
      immunohistochemistry) allows a more correct definition of this neoplasm,
      permitting a differential diagnosis with other tumours (lymphoma, medullary
      carcinoma, hemangioblastoma) with which in the past it has been erroneously
      identified. The results reported in the literature are controversial as regards
      long-term survival, but usually it is less than one year. Longer survival must
      lead to the suspicion of wrong diagnosis. A relatively better prognosis is
      observable in intraglandular forms, "minimi" neoplastic focus and young patients.
      The presence of regional metastatic lymph nodes doesn't seem to modify the
      prognosis. Instead, a factor which can condition the prognosis is the type of
      therapy. Now a days the most efficacious curative treatment is the multinodal one
      (surgery, radio- and chemotherapy). The best results about survival and quality
      of life have been obtained using chemo-radiotherapy before operation and
      chemotherapy after it.

PMID- 8152561
TI  - [Poorly differentiated "insular" carcinoma of the thyroid: long-term survival].
AB  - Poorly differentiated "insular" thyroid carcinoma is a rare, aggressive and often
      lethal variant of thyroid cancer. Thirty-one cases of this entity were
      encountered over a 18-yr period. In most of them surgical therapy consisted of
      total or near-total thyroidectomy. Six patients had distant metastases and/or
      mediastinal or tracheal infiltration at presentation. Fifteen out of 25
      apparently cured after surgery (60%) developed recurrence in the neck and/or
      distant sites. Radioiodine was employed to destroy thyroid remnants (22 cases)
      and subsequently to treat persistent/recurrent disease (17 cases). Thirteen
      patients showed radioiodine uptake in neoplastic lesions and in 3 cases complete
      resolution was observed. After a mean follow-up of 4.5 years (range 1-16) 6
      patients had died of their tumor, 12 are alive with persistent/recurrent disease,
      13 do not show any evidence of disease. This experience confirms that "insular"
      carcinoma tends to have an aggressive behavior, but therapy can be effective.
      Recognition of this entity is therefore important for planning adequate surgical
      approach and subsequent patient management.

PMID- 8152562
TI  - [Parathyroid transplantation and cryopreservation techniques].
AB  - This report reviews several aspects of parathyroid transplantation, including
      some technical aspects of cryopreservation. The problems concerning the control
      of autograft are also presented, with a little review of the more recent
      references. These results lead to the recommendation that total parathyroidectomy
      and autotransplantation should be considered as the method of choice in the
      treatment of secondary hyperparathyroidism.

PMID- 8152563
TI  - [Short-stay in patients surgically treated for thyroid disease].
AB  - The improvement in anesthesiology and greater experience of medical staff have
      permitted short-stay surgery. The authors in this pages report their knowledge of
      thyroid short-stay surgery. Their series numbers twenty-two lobectomies for
      uninodular the thyroid disease and one enucleoresection for a nodule of pyramidal
      lobe. Short-stay surgery has been proposed to euthyroid patients, selected
      according to age, residence and health (lack of associated pathologies such as
      cardiopathy, bronchopathy, hepatopathy, nephropathy, allergy, calcemic disorders
      and dysphony) and confirmed in the presence of histological extemporary diagnosis
      of "adenoma" (21 cases). The histological extemporary diagnosis of "carcinoma"
      has lengthened hospital stay. Among the lobectomies, 21 were executed in general
      anaesthesia and 1 in acupuncture. The enucleoresection was executed in local
      anaesthesia. Only in eighteen cases was a "Penrose" deainage used, removed after
      24 hours. The choice of thyroid short-stay surgery, particularly in day-hospital,
      must arise from a careful selection of patients. Besides, this surgery requires
      an administrative and sanitary structure which permits a constant patient's check
      at hare too.

PMID- 8152564
TI  - [Gastroenterologic pathology and replacement organotherapy in thyroidectomized
      patients].
AB  - Thyroid replacement therapy in patients treated by near-total or total
      thyroidectomy, as well as spontaneous hypothyroidism , can be difficult in
      patients with alterations in absorption functions or specific gastroenteric
      diseases. We have studied 25 patients, 22 women and 3 men, 18-72 years old (mean
      47 years), affected by spontaneous or post-surgical hypothyroidism, who
      presented, during the usual replacement therapy, persistently elevated or high
      normal TSH levels, and therefore required repeated variations in the prescribed
      dose of thyroxine. In these patients we evaluated hormone pattern, the presence
      of autoantibodies (anti-tyroglobulin, anti-Sm, anti-DNA, anti-microsomal
      antigens, anti-gliadin and anti-parietal cell), and performed an
      esophagogastroduodenoscopy (EGD) with histological examination. In all patients,
      plasma TSH ranged from 2.5 to 20 microU/ml. Only 17% of patients exhibited the
      presence of antibodies against thyroglobulin, 17% of patients had antibodies
      against microsomal antigens, 6% of patients presented antibodies against nuclear
      antigens; 4% had against gliadin. Histological examination revealed chronic
      gastritis (98%) with atrophic aspects (20%) and intestinal metaplasia (28%); and
      chronic duodenitis (86%) with villus abnormalities (23%) and total villus atrophy
      (4%). We underline the case of a patient, treated by total thyroidectomy for
      papillary carcinoma, who presented, two months after starting L-thyroxine
      therapy, a recurrence of celiac disease, that had been silent after childhood.
      The EGD showed, at the level of the second duodenal segment, a reduction of
      number and thickness of mucosal folds; the histological examination showed total
      villus atrophy, elongated crypts and a dense infiltration of chronic inflammatory
      cells in the lamina propria. Our experience underlines the frequent association
      of gastroenteric disease and hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152565
TI  - [Adrenal gland cysts. Our experience].
AB  - Adrenal cysts are an uncommon finding, in most cases unexpectedly discovered in
      the evaluation of nonspecific abdominal pain or at autopsy. Cystic adrenal masses
      can be classified into neoplastic and non-neoplastic aetiologies. The distinction
      between malignant and benign adrenal cysts can still be difficult. Cysts of
      neoplastic aetiology occur as a result of necrosis and cystic degeneration within
      both benign and malignant tumours. Non-neoplastic cysts have been conventionally
      divided into four categories: endothelial (45%), haemorrhagic or pseudocystic
      (39%), epithelial (9%) and parasitic (7%). Small adrenal cysts are clinically
      silent, while cysts of large size can cause displacement and compression of
      adjacent organs. The radiological aim is to detect the adrenal mass and CT is
      regarded as the best method available for this detection, although a
      differentiation between benign and malignant tumours can be difficult. Here we
      report our experience in nine patients with adrenal cysts. Abdominal pain was the
      dominant sign, two patients were hypertensive, one presented a palpable mass at
      abdominal examination and another presented oligomenorrhea with hypertrichosis,
      in five patients the adrenal mass was discovered unexpectedly during radiologic
      examination. All cysts in our patients were unilateral. All patients were
      examined by ultrasound and CT, one by RM, three by 75Se-Seleniumcholesterol
      cortical scintigraphy and two by 131I-MIBG medullary scintigraphy. In three
      patients a percutaneous aspiration of the cyst was performed via a posterior
      approach with CT or US guidance. This approach has been used for diagnostic and
      therapeutic purposes. Examination of aspirated cyst fluid for steroid hormones
      showed markedly elevated cortisol levels compared with normal plasma cortisol
      levels in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152566
TI  - [A case of adrenal adenoma with radiologic "cystic" appearance associated with
      hypophyseal adenoma].
AB  - Expansive lesions of the adrenal glands without signs of hormonal hypersecretion
      are usually discovered "incidentally", and are therefore called "incidentalomas".
      Since the silent adrenal masses constitute a heterogeneous group of lesions, the
      most important issue raised by the identification of these masses is their
      possible malignant potential. Therefore, the age and sex of the patients, the
      size of the mass, its imaging characteristic and its histologic features are the
      most important factors in the assessment of nonfunctioning adrenal masses. We
      report here the case of a women, aged 43 years mild hypertension, harbouring a
      great adrenal mass of 8 cm diameter, with cystic appearance at CT scan and
      ultrasonography, it did not show any uptake after 75Se-Seleniumcholesterol or
      131I-Metaiodobenzyl-guanidine. The patient was also affected by mild
      hyperprolactinemia caused a small pituitary adenoma. After selective venography,
      she underwent the surgical removal of the left adrenal gland with its mass, which
      showed a hystological picture of adrenal adenoma. The postoperative course was
      clinically normal. The interest of this case resides: in the dimensions of the
      adrenal tumor (the presence of adenomas greater than 6 cm diameter is extremely
      rare); in the radiographic findings, showing a cystic appearance, probably
      related to a fluid component, in the association of adrenal and pituitary
      adenoma, as a possible variant of multiple endocrine neoplasia (MEN) of type
      I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152567
TI  - [Reevaluation of the I-dopa test in acromegaly: anatomo-clinical and prognostic
      correlations].
AB  - It is known that in acromegalic patients the GH secretion exhibits a pattern of
      response to various stimuli that differs from that observed in normal subjects.
      We have evaluated the paradoxical GH response to 1-Dopa in acromegaly, in order
      to clarify the relationships between this datum and the tumour size, the basal GH
      secretion, the GH response to TRH and the long-term prognosis. MATERIALS AND
      METHODS. 34 acromegalic patients, 12 men and 22 women, aged 35-70 yr,
      participated in this study. They were divided in 4 classes, according to Hardy's
      classification of pituitary neoplasias: (1) intrasellar microadenomas, < 10 mm (n
      = 8); (2) intrasellar macroadenomas, > 10 mm (n = 14); 3) adenomas with local
      expansion (n = 9); (4) adenomas with extrasellar expansion (n = 3). All patients
      underwent a 1-Dopa-test; 18 of them underwent a TRH-test. Basal postoperative GH
      and basal pre- and postoperative PRL levels were also determined. RESULTS. The
      basal preoperative GH values in all patients ranged between 16 and 278 ng/ml. 22
      patients showed a paradoxical response to 1-Dopa, 12 were non-responders. The
      following results were observed in the different classes: [table: see text]
      Moreover, 10 subjects (56%) were TRH-responders (9 of them were also 1-Dopa
      responders, 1 was non-responder) and 8 were TRH non responders (6 were 1-Dopa non
      responders, 2 were 1-Dopa responders). Basal postoperative GH values were > 5 in
      17 1-Dopa responders and in 9 non responders. Basal preoperative PRL levels were
      > 25 ng/ml in 7 1-Dopa responders and in 2 non responders. After surgery, basal
      PRL became normal in 5 responder patients. DISCUSSION. In a previous work we have
      correlated the paradoxical GH response to TRH with tumour size and GH levels,
      observing a higher percentage of paradoxical response in patients in class I and
      II and, postoperatively, lower GH levels in preoperative TRH responders. So, we
      have underlined the good prognostic feature of a preoperative paradoxical
      response. In this paper we have evaluated the paradoxical GH response to 1-Dopa
      in the different Hardy's classes and compared it with the GH levels and the GH
      response to TRH. The results show that a paradoxical response can be observed
      more frequently in small (class I) adenomas than in greater size ones, and in
      presence of lower GH basal levels. Moreover, a concordance between 1-Dopa and TRH
      tests can be observed. CONCLUSIONS. The results clearly indicate that the
      responses to dynamic GH tests should be evaluated considering the anatomic
      characteristics of the neoplasias. It could be suggested that the paradoxical
      response can be expressed only when hypothalamus-pituitary interactions are
      intact.

PMID- 8152568
TI  - [Surgical complications in renal transplantation].
AB  - Technical complications in kidney transplantation are unusual but with a high
      incidence of graft loss and mortality. The authors report their experience with
      89 kidney transplants with an overall incidence of 16.8%. Only early and
      aggressive surgical procedures can resolve certain of the complications.

PMID- 8152569
TI  - [The "BTE"(basic knowledge--training--execution) method for teaching-learning
      surgical procedures].
AB  - For teaching-learning operative procedures the authors propose a new method
      ("KTE" method) in three progressive phases (step "K" or "basic knowledge"; step
      "T" or "training"; step "E" or "execution") that allow the student to achieve
      gradually the psychomotorial adaptation needed for the correct execution of
      surgical procedures. After preliminary study of the general features of the
      procedure (step B1) the student learns its operative features (step B2) on
      appositely constructed didactical tools ("Self-learning and learning maintenance
      boxes") that, together with the "observational" training (step A1), allow him to
      create in his mind an "operation image" and then, following an "operative"
      simulators training (step A2), to pass from that image to its carrying out
      (psychomotorial adaptation) that in the last phase (steps E1 and E2) concludes in
      the partial or complete execution of the surgical procedure in the patient. This
      didactic method can be apply to classic or endoscopic surgery and even to a lot
      of not surgical practical procedures.

PMID- 8152570
TI  - [Autotransfusion in general surgery].
AB  - Self-transfusion represents a clinical method used for the restoration of
      haematic losses that, in recent years has been employed more and more widely in
      the surgical ambit. The utilisation of this method has become increasingly
      frequent because of the high diffusion of haemotransmitted diseases, and of the
      incidences, not negligible, of complications relative to the transfusions of
      homologous blood. The techniques that are currently used are: self-donation with
      predeposit; inter-surgery recovery; hemodilution normal blood volume. From 1989
      until now 260 patients have been performed, in the Institute of III Surgical
      Clinic of University of Rome, to self-transfusional method with predeposit and
      intersurgery recovery. In practice this technique did not present any
      complications.

PMID- 8152571
TI  - [Autohemotransfusion in cardiac reoperations].
AB  - OBJECTIVE: To evaluate the efficacy of intraoperative autotransfusion with
      hemodilution (AHT) to reduce postoperative transfusion of blood or blood products
      (BT) after cardiac surgery reoperation. DESIGN: Retrospective study, follow-up
      control. SETTING: Italian Institution of Cardiac Surgery (IICC). PATIENTS: 169
      patients (51 males, 118 females; mean age 49.5 years) undergoing a reoperation
      from May 1982 to December 1991. INTERVENTIONS: 143 patients single valve
      replacement, 16 patients double valve replacement and 10 patients radical
      correction for tetralogy of Fallot. AHT (mean 620.2 +/- 226.9 ml) was performed
      in all patients. The shed blood was reinfused at the end of the surgery. PT, PTT,
      TT, TT Coagulase, FDP, pre- and postoperative platelet count, bleeding and needs
      for BT were recorded. RESULTS: Preoperatively: PT 71.3 +/- 8.1, PTT (sec.) 36.9
      +/- 3.5, TT (sec.) 16.2 +/- 2.3, TTC (sec.) 16.9 +/- 1.7, FDP (ng% ml) 3.8 +/-
      2.7, Platelet count (No./mu 11 170 +/- 58. Postoperatively: PT 36.5 +/- 6.5,
      PTT(sec.) 49.5 +/- 8.7, TT(sec.) 19.1 +/- 1.8, TTC(sec.) 18.9 +/- 2.1, FDP (ng%
      ml) 13.5 +/- 8.9, Platelet count (No./mu 11) 85 +/- 34. We had one reentry
      because of bleeding. The mean units of blood or blood products need after surgery
      were 2.2 +/- 1.02. Bleeding from the drainage was 105.2 +/- 103.8. Two patients
      died in the postoperative period because of low output syndrome. In a period of
      one year of F.U. we had only one patient with hepatitis B. CONCLUSIONS: These
      data suggest that AHT is a safe method, reduces needs for banked blood or blood
      products, risks of infectious disease transmission and of immunologic reactions
      and presents hemorheologic benefits because of the diminished blood viscosity.

PMID- 8152572
TI  - [Office surgery: organization, legislative, and medico-legal problems. Personal
      experience].
AB  - INTRODUCTION: The authors approach the subject of office surgery by underlining
      the advantages of this procedure. In particular, they focus attention on the
      anesthesiological and legislative problems. Depending on the setting used for
      surgery and the duration of hospitalisation, ambulatorial surgery can be divided
      into: day-hospital, office surgery, one-day surgery, short-stay surgery, same-day
      surgery, MATERIALS AND METHODS: The authors report their own experience relating
      to 103 cases with relative complications. A total of 103 operations of medium-to-
      major ambulatorial surgery were performed (100 females and 3 males, mean age
      36.8). One week prior to surgery all patients attended a medical out-patient
      examination in order to fill in medical records and be prescribed routine
      hematochemical tests, chest X-ray and ECG. The preoperative anesthesiological
      evaluation was made at the time of surgery. All patients received antibiotic
      prophylactic treatment. RESULTS: Postoperative complications were reported above
      all following neuroleptoanalgesia and amounted to a total of 5 cases: nausea (4
      cases) associated with vomit (1 case), and postural hypotension (1 case). No
      infective complications were observed. DISCUSSION AND CONCLUSIONS: The authors
      emphasise the importance of a careful preoperative selection of patients; an out
      patient structure equipped with the appropriate instrument and machinery for
      surgery and the constant presence of anesthetists to ensure correct anesthesia
      (local, neuroleptoanalgesic, peridural general), reanimation and postoperative
      care. The aims of ambulatorial surgery are, in broad terms, the safety of
      procedures, convenience for the patient and organisational and economic savings
      for health structures. Ambulatorial surgery has an extremely high acceptance rate
      by patients. Lastly, the authors also report the juridical and bureaucratic
      problems faced by ambulatorial surgery and look forward to its wider diffusion.
      In the future office surgery might represent an important contribution to
      surgical therapeutic strategies, allowing, if well organised, an excellent
      compromise between safety, convenience and reduced costs for the patient.

PMID- 8152573
TI  - [Analysis of biomedical imaging with adaptive fractionated techniques].

PMID- 8152574
TI  - [Respiratory function and cardiovascular risk factors. Research Group for the
      Integrated Community Control of Chronic-degenerative diseases in the Health
      District of Sezze -- Di.S.Co. -- Observational strategy to assess the community
      health status].
AB  - Within the Project Community Control of Chronic Diseases in the Health District
      of Sezze-Di.S.Co.-2940 men, aged 20-69 were examined between 1984 and 1987, and a
      pulmonary function test was performed together with the measurement of a number
      of cardiovascular risk factors. Blood tests, blood pressure, anthropometric
      measurements, ECG, spirometry and a questionnaire on life-style and diseases were
      available. The aim of this paper was to describe pulmonary function tests and to
      study their association with cardiovascular risk factors. Vital capacity (CV) and
      forced expiratory volume in one second (VEMS), adjusted by height were inversely
      related with age. Main cardiovascular risk factors were analysed in tertiles of
      CV and VEMS: fasting blood glucose, serum cholesterol, uric acid, haematocrit,
      diastolic blood pressure, number of cigarettes per day decreased going from the
      first to the third tertile, whilst HLD-cholesterol and alcohol consumption
      increased. Univariate and multivariate analysis showed an inverse relation of CV
      and VEMS with age, fasting blood glucose, number of cigarettes smoked per day,
      uric acid, heart rate, skinfold thickness whilst alcohol consumption and weight
      were inversely related. The models explained between 52% (VC) to 57% (VEMS) of
      the variance.

PMID- 8152575
TI  - [Tropisetron versus ondansetron in the prevention and control of emesis in
      patients undergoing chemotherapy with FAC/FEC for metastatic or surgically
      treated breast carcinoma].
AB  - OBJECTIVE. To compare the efficacy and tolerability of standard dosage of
      tropisetron and ondansetron in controlling emesis induced by chemotherapeutic
      regimen not containing cisplatin. DESIGN. Open, comparative, parallel-group,
      randomized study. SETTING. Day hospital to which patients were admitted only on
      the day on chemotherapy when the antiemetic was given intravenously. PATIENTS:
      Forty adult women with metastatic or operated breast cancer who could benefit by
      adjuvant treatment. EXCLUSION CRITERIA: pregnancy, breast-feeding, symptoms of
      intracranial hypertension, current medical conditions which could put the patient
      at risk (e.g. severe cardiac insufficiency, uncontrolled infection, etc.),
      abnormal bowel rhythm, and treatment with antitumoral drugs in the previous 6
      months. TREATMENT. During three cycles of chemotherapy with FAC/FEC (600 mg/m2 5
      fluro-uracil, 600 mg/m2 cyclophosphamide and 50 mg/m2 adriamycin or 60 mg/m2
      epidoxorubicin) antiemetic treatment was given as follows: tropisetron 5 mg/day
      (in intravenous infusion before chemotherapy and then orally for 4 days) or
      ondansetron 8 mg x 3/day (the first dose intravenously before chemotherapy and
      the subsequent doses orally until the end of the fourth day after chemotherapy).
      OUTCOME MEASURES: Severity of nausea and number of vomiting episodes each day
      during antiemetic treatment; ECG; vital signs and blood tests before each cycle
      and at the end of the study; side effects. RESULTS: On the worst day of the three
      cycles complete control of emesis was obtained in 50, 75 and 84.6% of the
      patients treated with tropisetron and in 60, 58.8 and 66.7% of those who received
      ondansetron, the differences being not significant (p > 0.05). The only side
      effects were headache (in 1 patient given tropisetron) and skin rash (1 given
      ondansetron). CONCLUSIONS: The efficacy and tolerability of 5 mg/day of
      tropisetron and 24 mg/day of ondansetron were almost identical.

PMID- 8152576
TI  - [Comparative study of the effectiveness of imipenem versus ceftazidime and
      ceftriaxone in the prevention of postoperative infections].
AB  - A comparative study was performed on the efficacy, safety and tolerability of
      three different antibiotics (imipenem, ceftazidime, ceftriaxone) in the
      prevention of postoperative infection. Evaluations were made on the basis of the
      results obtained in a group of 90 patients subdivided into three matched groups
      each of which was treated with one of the three compounds. The trend of cutaneous
      temperature showed differences at the limit of significance (p congruent to
      0.05). Variations in leucocyte concentrations showed an analogous pattern in all
      patients, although there were fewer and with a shorter duration in subjects
      treated with imipenem. The wound healing process was improved in patients
      receiving prophylactic antibiotic treatment in the form of imipenem (0.01 < p <
      0.05) who also showed a greater respect for therapeutic protocols (80%), a higher
      percentage of remission of fever and a shorter mean hospital stay (9 days). In
      the light of these preliminary results the authors express their favourable
      judgement regarding the choice of imipenem for the prophylaxis of postoperative
      infection; however, each of the three protocols showed a considerable
      prophylactic capacity as well as good tolerability and ease of use.

PMID- 8152577
TI  - [Diarrhea associated with antibiotic therapy].
AB  - The authors suggest rational procedures to prevent the antibiotic associated
      diarrhea (AAD) Clostridium difficile positive or not, considering its high cost
      (both to stay in Hospital and for specific therapy). Twenty-four cases of
      diarrhea starting during antibiotic therapy and until one month from its
      interruption was assessed. Twelve (50%) was found Clostridium difficile (+); 12
      (50%) was Clostridium difficile (-); no case of pseudomembranous colitis was
      found. Two hospitalized patients shared the room with others suffering from
      diarrhea Clostridium difficile (+) developing the same illness although
      precautions were used both by physicians and by nursing staff. Four patients had
      diarrhea after domiciliary antibiotic therapy. Vancomycin (1-2 g/die p.o.) was
      effective therapy in patients with important diarrhea (more than 10 withdrawals
      in a day). Two cases with moderate diarrhea (less than 6 withdrawals in a day)
      Clostridium difficile (+) recovered without antibiotic therapy. The authors
      propose: a) rational antibiotic use; b) isolation of affected patients; c)
      sanitary measures in dejections treatment.

PMID- 8152578
TI  - [Lyme disease. Case contribution and review of the literature].
AB  - Lyme borreliosis is a systemic disease. The etiologic agent is a tick-bite borne
      spirochete (Borrelia burgdorferi) of which men are casual hosts. Although the
      illness is reported worldwide, it is more frequent in the northern parts of
      Countries. Some isolated clinical pictures are reported in the past, but only in
      1975 the illness was well described at Old Lyme (Connecticut, Usa) and then well
      defined in its pathogenesis and clinical course in three stages. Lyme disease,
      involving skin, heart, nervous system and joints, is frequently protean and
      misdiagnosed, so that it was called "the new great imitator". In Italy the first
      case is reported in 1985. The authors report three (3) new cases, mostly with
      neuro-articular signs and symptoms. Literature is partially reviewed, for a
      better definition and outline of some epidemiological, etiopathogenetic,
      historical and clinico-therapeutic aspects of Lyme disease.

PMID- 8152579
TI  - [Suicide and burial practice in the Bible].

PMID- 8152580
TI  - [Kinetics of breast neoplasms].
AB  - Breast cancer is a disease moderately responsive to chemotherapy. While its
      curability is inversely related to the tumor burden, a relevant number of
      patients still progress to metastatic disease even after adjuvant chemotherapy.
      Also, high-dose chemotherapy appears promising, but can not yet be considered
      ultimately curative of breast cancer. Different variables, biological, kinetic
      and treatment-related, account for the clinical behaviour of this disease. In
      order to improve its curability, they will all need to be taken into account in
      planning future treatment strategies. One of the most effective ways to
      understand and predict the clinical behaviour of breast cancer is the development
      of appropriate mathematical models explaining its growth-patterns. Aim of this
      paper is to review the two fundamental models, the exponential and the
      Gompertzian. The exponential model is at the basis of the Skipper-Schabel and the
      Goldie-Coldman hypotheses, while the Norton-Simon hypothesis has been formulated
      from the gompertzian model. The latter appears to better fit the vast amount of
      clinical data which are presently available: from Bloom's analysis of untreated
      breast cancer patients, to the results of large clinical trials, to the data
      emerged from the recent meta-analysis. Characteristic of a gompertzian growth
      pattern is that exponential growth is matched by exponential retardation of
      growth. In 1943 Delbruck and Luria demonstrated that random mutations could
      account for the development of virus resistance in bacteria and were able to
      estimate the rate of mutation as a function of the growth rate of bacteria.
      Shortly after Law demonstrated that resistance to methotrexate in murine leukemia
      occurred similarly. The concept of combination chemotherapy actually derived from
      the idea that cancer cells could be resistant to chemotherapy even before
      exposure to it. Goldie and Coldman applied the Delbruck/Luria model to
      hypothesize the use of non cross-resistant alternating combination chemotherapy
      as a better way to eliminate the risk of resistance. They also suggested that
      many different drugs were to be used as soon as possible, when the tumor size is
      still small. Most of their predictions were based on the Skipper/Schabel model of
      the exponential growth of cancer and on its deriving log-kill model. A large
      amount of clinical data are now suggesting that the behaviour of breast cancer is
      best described by gompertzian growth: in particular, gompertzian growth is a
      tenable model of breast cancer growth for both the unperturbed and the perturbed
      (by treatment) states.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8152581
TI  - Frontal lobe dementia is not a variant of prion disease.
AB  - Frontal lobe dementia (FLD) is a syndromal diagnosis with a variable pathology.
      It has been argued that FLD is a dementing disorder which should be nosologically
      and etiologically distinguished from other types of dementia. However,
      similarities with prior disease and Alzheimer's disease have led to the
      suggestion that FLD is a variant of one or other of these dementias. We have
      tested this line of argument by examining the frontal cortex and cerebellum of 14
      FLD cases and probing the molecular pathology using well characterized antibodies
      to prion protein and beta-amyloid protein. No prion protein deposits or
      significant levels of beta-amyloid protein were detected. FLD is a dementing
      disorder whose molecular pathology, whilst as yet uncharacterised, can be
      distinguished from those of other dementing disorders.

PMID- 8152582
TI  - Gene expression and transcript size of the prepro-peptide VIP/PHM-27 in normal
      human tissue.
AB  - The transcript size of VIP/PHM-27 mRNA (vasoactive intestinal peptide/peptide
      histidine methionine) and the relative distribution of VIP/PHM-27 gene expression
      in 10 normal human tissues was examined. After mRNA extraction from tissue,
      VIP/PHM-27 transcript size and relative abundance of mRNA was determined by
      Northern blot analysis and densitometry of the autoradiograms. VIP/PHM-27 mRNA
      was detectable in brain, pancreas, colon, ileum and striated muscle while no
      hybridization signal was observed in liver, kidney, lung, heart, prostate and
      placental tissue. VIP/PHM-27 transcript in human brain and gut was a single band
      of 1.7 kb; by contrast, a 7.0-kb transcript was detected in striated skeletal
      muscle. The highest relative levels of mRNA were observed in brain and pancreas.

PMID- 8152583
TI  - Sleep homeostasis in the guinea pig: similar response to sleep deprivation in the
      light and dark period.
AB  - In the guinea pig, sleep and slow-wave activity (SWA) are evenly distributed over
      24 h in contrast to the sleep pattern in other rodents where a daily preference
      for sleep and a decline of SWA within the main sleep period is typical. SWA is
      regulated as a function of prior waking and is assumed to reflect sleep
      intensity. We investigated sleep homeostasis and its possible circadian
      modulation by performing sleep deprivation (SD) at two phases of the light-dark
      cycle. SD induced an increase in SWA which was similar under both conditions. We
      conclude that sleep is homeostatically regulated in the guinea pig and is not
      subject to a circadian modulation.

PMID- 8152584
TI  - N-methyl-D-aspartate receptors but not non-N-methyl-D-aspartate receptors mediate
      hypertension induced by carotid body chemoreceptor stimulation in the rostral
      ventrolateral medulla of the rat.
AB  - In urethane-anesthetized rats, excitatory amino acid antagonists were
      microinjected into the rostral ventrolateral medulla (RVLM) and their effects on
      the pressor response and tachycardia evoked by carotid chemoreceptor stimulation
      were examined. Microinjections of the N-methyl-D-aspartate (NMDA) receptor
      antagonists 2-amino-5-phosphonovalerate (AP5) and MK-801 into the RVLM inhibited
      these chemoreceptor reflex responses whereas these responses were not affected by
      injection of the non-NMDA receptor antagonist CNQX. AP5 and MK-801 but not CNQX
      abolished the pressor response evoked by NMDA whereas CNQX but not AP5 and MK-801
      abolished that evoked by AMPA or kainate. These results provide evidence that
      NMDA receptors in the RVLM of the rat are involved in the carotid chemoreceptor
      reflex.

PMID- 8152585
TI  - Increased expression of subunit c of mitochondrial ATP synthase in brain tissue
      from neuronal ceroid lipofuscinoses and mucopolysaccharidosis cases but not in
      long-term fibroblast cultures.
AB  - Recent data showed storage of subunit c of mitochondrial ATP synthase in late
      infantile, juvenile, and adult forms of neuronal ceroid lipofuscinosis (NCL). The
      present study demonstrates that the expression of subunit c in NCL fibroblasts in
      long-term cultures, both grown in standard conditions and after leupeptin and
      ammonium chloride treatment, is not greater than in controls. It indicates that
      as a result of yet undefined factors, NCL fibroblasts in long-term cultures, lose
      their ability to accumulate subunit c. Moreover, both Western blot analysis of
      brain tissue homogenates and immunohistochemistry showed increased
      immunoreactivity to subunit c in mucopolysaccharidosis type I and III. This
      increased subunit c expression in a disorder with impaired lysosomal function
      other than the NCL supports the hypothesis that accumulation of this proteolipid
      might be related to its defective degradation.

PMID- 8152586
TI  - Cytokine-induced neutrophil chemoattractant mRNA expressed in cerebral ischemia.
AB  - Cytokine-induced neutrophil chemoattractant (CINC), originally identified as a
      chemoattractant in rat kidney epithelial cells, is related to human 'gro' and
      murine 'KC'. The proteins encoded by these genes belong to the chemokine alpha
      superfamily, most of which have neutrophil chemotactic activity. Since brain
      chemokines may play a significant role in neutrophil accumulation in cerebral
      ischemia which can contribute to the extent of tissue injury in stroke, we
      examined the expression of CINC mRNA in the cerebral cortex of rats subjected to
      focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO).
      Significant CINC mRNA expression was observed in the ipsilateral (ischemic)
      cortex from 6 h (17.3 +/- 3.7%, n = 6, P < 0.05) to 24 h (32.1 +/- 3.7%, n = 5, P
      < 0.01) with a peak at 12 h (43.9 +/- 3.7%, n = 6, P < 0.01) after MCAO. Five
      days post-MCAO, CINC mRNA levels were no longer elevated. No significant CINC
      mRNA expression was observed in the contralateral (control) cortex. These studies
      suggest that message for the neutrophil chemoattractant CINC is induced early in
      brain tissue subjected to ischemia, and therefore supports the possibility that
      brain-derived chemokines support the infiltration of circulating inflammatory
      cells following focal stroke.

PMID- 8152588
TI  - Projection of the inferior dental nerve to the primary somatosensory cortex in
      rats.
AB  - We observed perioral representations in the primary somatosensory cortex in rats
      to identify the location of the tooth region. Field potentials evoked by
      stimulation of an inferior dental nerve were mapped on a surface of the cerebral
      cortex. Stimulation of the nerve bilaterally evoked biphasic (positive-negative)
      or triphasic (positive-negative-positive) field potentials with contralateral
      predominance. The focus of the field potentials was located in the rostral region
      of the lower jaw zone of the somatosensory map, as visualized in a flattened
      cerebral hemisphere, using cytochrome oxidase histochemistry.

PMID- 8152587
TI  - Comparative electrophysiological properties of NG108-15 cells in serum-containing
      and serum-free media.
AB  - The electrophysiological properties of NG108-15 neuroblastoma x glioma hybrids
      were compared after culture in serum-containing medium (SCM) versus serum-free
      media (SFM) containing N2 or B27 supplements. The excitability of cells was media
      dependent (B27 > N2 > SCM). Action potential profiles of SFM cells were
      characterized by slower activation and prolonged after hyperpolarization which
      predisposed SFM cells to fire repetitively. The presence of three types of inward
      calcium currents was also revealed in SFM cells. These differential effects were
      primarily attributable to the media used with a secondary enhancement by the
      chemical differentiating agents used (dB-cAMP and forskolin).

PMID- 8152589
TI  - Baclofen inhibits high-threshold calcium currents with two distinct modes in rat
      hippocampal neurons.
AB  - In primary cultures of hippocampal neurons, activation of GABAB receptors
      reversibly inhibits high-voltage activated (HVA) Ca currents. In some neurons the
      GABAB agonist baclofen produces slow down of Ca current activation. In these
      cells the inhibitory action of the agonist can be relieved by strong pre
      conditioning depolarizations. In other cells, where no significant changes in
      activation kinetics could be observed during agonist application, conditioning
      prepulses are nearly ineffective to recover the current from inhibition. Thus, in
      hippocampal neurons, activation of GABAergic receptors can modulate Ca currents
      with two different modes: one is voltage-dependent and the other is voltage
      independent. In the presence of omega-conotoxin (omega-CgTx), only the second
      mode is prevented, suggesting that the two modulatory mechanisms (voltage
      dependent and voltage-independent) operate in different cells on separate classes
      of HVA Ca channels.

PMID- 8152590
TI  - Basal extracellular dopamine in the nucleus accumbens during amphetamine
      withdrawal: a 'no net flux' microdialysis study.
AB  - The basal extracellular concentration of dopamine in the nucleus accumbens was
      quantified using the 'no net flux' microdialysis method, in rats undergoing
      withdrawal from D-amphetamine. Rats were initially pretreated with saline, or an
      escalating dose amphetamine regimen known to produce a robust withdrawal
      syndrome, and extracellular dopamine was quantified 3 or 28 days after the last
      pretreatment injection. There was no effect of amphetamine pretreatment on the
      basal extracellular concentration of dopamine in the nucleus accumbens, or on the
      'in vivo recovery' of dopamine, estimated by 'no net flux' microdialysis. It is
      suggested that amphetamine withdrawal is not necessarily accompanied by changes
      in the basal extracellular concentration of dopamine in the nucleus accumbens.

PMID- 8152591
TI  - Melatonin counteracts pinealectomy-dependent decreases in rat brain
      [3H]flunitrazepam binding through an opioid mechanism.
AB  - The effect of intracerebroventricular (i.c.v.) injection of melatonin and/or beta
      endorphin on the [3H]flunitrazepam binding sites in the cerebral cortex of
      pinealectomized or superior cervical ganglionectomized rats was studied.
      Pinealectomy decreased the maximum concentration of benzodiazepine receptors
      (Bmax) without affecting the dissociation constant (KD), while melatonin,
      ineffective in control animals, counteracted the effect of pinealectomy.
      Intracerebroventricular injection of beta-endorphin increases Bmax in both
      control and pinealectomized animals, the effect being significantly higher in the
      latter. Simultaneous i.c.v. injection of melatonin + beta-endorphin did not
      further increase Bmax in any group, whereas i.c.v. injection of naloxone
      significantly blocked the effects of melatonin and/or beta-endorphin
      administration. Pineal sympathetic denervation produced a significant increase in
      Bmax and KD, whereas i.c.v. injection of melatonin further increased the former,
      restoring KD to control values. Neither i.c.v. administration of beta-endorphin
      or melatonin + beta-endorphin significantly modified the ganglionectomy-dependent
      increase in Bmax, although both treatments restored KD to control values.
      Naloxone administration had no effect on beta-endorphin- and melatonin + beta
      endorphin-treated ganglionectomized groups, but counteracted the increased effect
      of melatonin on Bmax in ganglionectomized animals.

PMID- 8152592
TI  - Low-threshold calcium current in dendrites of the adult rat hippocampus.
AB  - The patch-clamp technique was employed in hippocampal slices to examine the
      characteristics of a low-threshold Ca current in adult CA1 pyramidal neurons. We
      found that adult CA1 pyramidal neurons possess a distinct transient low-threshold
      Ca current, located predominantly in the distal dendrites. Surgical cuts that
      separated the dendrites from the soma and left a dendritic length of 150 microns,
      completely abolished the low-threshold Ca current while a transient K current
      persisted even in cells with dendrites as short as 50 microns. The transient low
      threshold Ca current in dendrites may represent a voltage-dependent Ca entry
      pathway which contributes to the regulation of cellular excitability, plasticity
      and pathology.

PMID- 8152593
TI  - Increase in c-erbA alpha 2 mRNA in the parvocellular region of the
      paraventricular nucleus of the hypothalamus following thyroidectomy in the adult
      male rat.
AB  - To examine thyroid hormone regulation of c-erbA alpha 2 mRNA expression in the
      parvo-cellular region of the paraventricular nucleus of the rat hypothalamus
      (pPVN), quantitative in situ hybridization was performed using 3H-labeled probe
      complementary to c-erbA alpha 2 mRNA. Thyroidectomy induced a significant
      increase in the number of silver grains overlying the cytoplasm in the pPVN
      relative to sham-operated controls. This effect was prevented by daily injection
      of thyroxine. These results indicate that hypothyroidism induced an increase in
      cellular c-erbA alpha 2 mRNA level in the pPVN.

PMID- 8152594
TI  - Alteration of brain and liver microsomal polyunsaturated fatty acids following
      dietary vitamin E deficiency.
AB  - The effects of dietary vitamin E deficiency on fatty acid composition of brain
      and liver microsomes were studied in rats fed a vitamin E-deficient diet for 9
      weeks. In brain microsomes, vitamin E deficiency resulted in a significant
      decrease in palmitic acid and total saturated fatty acids. Cervonic acid was
      increased. In contrast, no marked changes were observed in the levels of (n-6)
      polyunsaturated fatty acid (PUFA). In liver microsomes, vitamin E deficiency
      resulted in significant alterations in fatty acid composition: higher amounts of
      stearic acid and total saturated fatty acids, lower amounts of mono-unsaturated
      fatty acids, linoleic and dihomo gamma linoleic acids. In contrast, arachidonic
      acid was not altered. The overall decrease in the amounts of (n-6) PUFA was
      compensated by an increase in the level of (n-3) PUFA. It is concluded that
      vitamin E may alter the enzymatic activities of chain elongation-desaturation and
      the relationship between vitamin E and PUFA in brain and liver microsomes.

PMID- 8152595
TI  - Inositol 1,4,5-trisphosphate arm of the phosphatidylinositide signal transduction
      pathway in the rat cerebellum during aging.
AB  - To determine whether the intracellular calcium-mobilizing second messenger,
      inositol 1,4,5-trisphosphate (InsP3) and its receptor (InsP3R) display age
      dependent coordinate regulation, InsP3 content and [3H]InsP3-binding
      characteristics were investigated in cerebellar particulate membranes prepared
      from male Fischer 344 rats at 3, 12 and 25 months of age. Cerebellar InsP3
      content was significantly increased in 25-month-old rats compared with 3-month
      old animals. Cerebellar InsP3R densities were significantly reduced at 12 and 25
      months of age but InsP3-binding affinity was significantly decreased only in the
      25-month-old animals. The present data strongly suggest that modulation of the
      phosphoinositide second messenger system may contribute to impaired neuronal
      responsiveness associated with the aging process in the cerebellum.

PMID- 8152596
TI  - The patterns of control signals underlying elbow joint movements in humans.
AB  - Position, velocity, flexor and extensor electromyographic (EMG) activity of fast,
      moderate and slow elbow movements to a target were recorded and simulated using a
      model in which reciprocal and co-activation central commands, proprioceptive
      feedback and mechanical properties of muscles were considered. Two hypotheses
      concerning the pattern of shift in the equilibrium point (EP) underlying the
      movements were tested. First, the nervous system specifies a constant rate of EP
      shift to produce movement and encodes displacement by the duration of the shift
      (ramp-shaped pattern). Second, in fast movements, the EP rapidly shifts towards
      the future final position but then shifts back and forth eventually reaching the
      final EP (N-shaped pattern). The ramp pattern was consistent with kinematic and
      EMG experimental data regardless of movement speed. In contrast, the N-shaped
      pattern was incompatible with the kinematic characteristics of fast movements.

PMID- 8152597
TI  - Receptive properties of afferent nerve fibres associated with the rat saphenous
      vein.
AB  - We tested afferent fibres isolated from the saphenous nerve for their responses
      to mechanical, osmotic and chemical stimuli applied to a vascularly isolated
      segment of the saphenous vein in the rat. Fifteen units were excited by local
      mechanical stimulation and many of them were also activated by distension of the
      venous segment, however exclusively by presumably noxious pressures. Most
      mechanosensitive fibres were excited by one of the three pain-producing
      substances, hyperosmotic saline (HS), potassium chloride (KCl) and bradykinin.
      Three fibres which were insensitive to mechanical stimulation, responded to
      injection of HS or KCl into the venous segment. We conclude that the venous
      afferents most likely have nociceptive function. Most are considered to be
      polymodal.

PMID- 8152598
TI  - 40-Hz oscillations during motor behavior in man.
AB  - 40-Hz oscillations were measured during finger, toe and tongue movement using an
      electrode array of 56 electrodes over the pre and post central areas. Each
      movement was made 150 times in intervals of 12 s. The average power increase in
      narrow frequency bands between 8 and 40 Hz was then calculated and the
      topographical distribution studied. 40-Hz oscillations were only found
      contralateral over the hand area for finger movements, close to the vertex for
      toe movements and bilateral symmetrical for tongue movements. The maxima of the
      40-Hz oscillations occurred before movement onset.

PMID- 8152599
TI  - Inhibitors of endocytosis, endosome fusion, and lysosomal processing inhibit the
      intracellular proteolysis of the amyloid precursor protein.
AB  - Degradation of the amyloid precursor protein (APP) by lysosomes has been proposed
      to be the mechanism for generation of the beta/A4 polypeptide which is the major
      constituent of amyloid plaques. In this report, we use inhibitors to elucidate
      the steps involved in the lysosomal degradation of APP in PC12 cells. Monensin
      treatment significantly elevated the level of immature APP. Reducing the
      temperature to 17 degrees C, adding cytochalasin B and colchicine, or exchanging
      K+ for Na+ resulted in a substantial accumulation of both mature and immature APP
      isoforms. The inhibitor of autophagy, 3-methyladenine, had no effect on the level
      of APP isoforms. These results suggest that changes in ionic balance, membrane
      fluidity or vesicle fusion may affect APP processing.

PMID- 8152600
TI  - Do anticipatory postural adjustments precede compensatory stepping reactions
      evoked by perturbation?
AB  - Many recent studies have revealed the consistency of anticipatory postural
      adjustments preceding single leg movements, such as stepping, in standing humans.
      These adjustments appear to involve an active lateral transfer of weight to the
      stance leg. The present study demonstrates that these anticipatory adjustments
      often do not appear in compensatory stepping responses evoked by postural
      perturbation. Compensatory stepping without anticipatory active weight transfer
      seemed to be more likely to occur when stepping was not pre-planned or when the
      perturbation characteristics were novel. The substantial variability seen in the
      anticipatory weight transfer, when it did occur, contrasts the consistency of the
      anticipatory responses seen in gait initiation and other non-compensatory leg
      movements. The results suggest that there may be fundamental differences in the
      control of compensatory versus non-compensatory stepping, and may provide insight
      into the sequencing of anticipatory postural reactions and subsequent leg
      movements.

PMID- 8152602
TI  - Bradykinin B1 and B2 receptor antagonists do not change the ongoing activity of
      slowly conducting articular afferents in the inflamed knee joint of the cat.
AB  - Arthritic hyperalgesia and pain result from an increased activity of nociceptive
      afferents that may be induced and maintained by inflammatory mediators like
      bradykinin (BK). The B1 receptor antagonist des-Arg9-Leu8-BK and the B2 receptor
      antagonists Thi5,8-D-Phe7-BK and Hoe 140 were used to study the involvement of BK
      receptors in the generation of ongoing afferent activity in the cat's knee joint
      that was inflamed by kaolin and carrageenin. After i.a. bolus administration of
      BK receptor antagonists (26-260 micrograms) close to the joint, the ongoing
      activity did not significantly vary in any group III or group IV unit. We
      conclude that activation of BK receptors by endogenous BK is probably not the
      mechanism that is responsible for the increased ongoing activity of articular
      afferents in the inflamed joint.

PMID- 8152601
TI  - Fos protein expression in the circadian clock is not associated with phase shifts
      induced by a nonphotic stimulus, triazolam.
AB  - Recent studies have shown that light-induced phase shifts of the circadian rhythm
      of locomotor activity are associated with c-fos expression in the suprachiasmatic
      nucleus (SCN) and intergeniculate leaflet (IGL) of the lateral geniculate nucleus
      of rodents. In order to determine whether c-fos expression is necessary for the
      phase shifting effects of a non-photic stimulus, we assessed Fos-like
      immunoreactivity (Fos-lir) in the SCN and IGL at various times after an injection
      of the short-acting benzodiazepine, triazolam, at circadian time (CT) 6; i.e. at
      a time when triazolam induces an acute increase in locomotor activity and maximal
      phase advances in the circadian rhythm of locomotor activity. Specific Fos-lir
      staining was not observed in the SCN or IGL regions of any animals treated with
      triazolam or vehicle at any time point examined. These results indicate that
      exposure to an activity-inducing stimulus at circadian times when this stimulus
      induces phase shifts does not induce Fos protein synthesis in the SCN or IGL
      regions.

PMID- 8152603
TI  - Neural projections of the pineal organ in the larval sea lamprey (Petromyzon
      marinus L.) revealed by indocarbocyanine dye tracing.
AB  - The distribution of the central neural connections of the pineal organ of the
      larval sea lamprey was investigated by means of anterograde and retrograde
      tracing with the fluorescent lipophilic dye, DiI (1,1'-dioctadecyl 3,3,3',3'
      tetramethylindocarbocyanine perchlorate). Pinealofugal projections are well
      developed in larvae, extending from the posterior commissure into the
      diencephalon and mesencephalon. Small numbers of neurons were retrogradely
      labelled in the transition zone between the diencephalon and the mesencephalic
      tegmentum. These cells may constitute the first pinealopetal system described in
      anamniotes.

PMID- 8152604
TI  - C-fos expression in arcuate nucleus following intracerebroventricular hypertonic
      saline injections.
AB  - Experiments were done in conscious rats to investigate the effect of i.c.v.
      infusions of hypertonic NaCl solutions on the induction of the protein Fos in the
      arcuate nucleus (Arc). Neurons containing Fos-like immunoreactivity were observed
      throughout the rostrocaudal extent of Arc after i.c.v. infusions of hypertonic
      saline solutions (337-744 mM). However, most of the labelled neurons were
      confined to the middle third of the nucleus, in the region of the dorsomedial and
      ventromedial subnuclei. Few, if any Fos-labelled neurons were observed in Arc of
      animals that received i.c.v. infusions of isotonic (142 mM) or mild hypertonic
      (173 mM) saline solutions or a hyperosmotic (660 mOsm/kg) saline solution of
      mannitol. No Fos-labelled neurons were found in the subfornical organ, although a
      few were observed scattered throughout the organum vasculosum laminae terminalis
      (OVLT) in all the animals studied. The density nor the distribution pattern of
      Fos-labelled neurons in OVLT was altered in animals receiving i.c.v. infusions of
      hypertonic saline or hyperosmotic solutions. These data demonstrate that Arc
      neurons are activated during a hypertonic saline challenge and suggest that Arc
      may function as a sodium-sensitive structure that is involved in body-fluid and
      circulatory homeostasis.

PMID- 8152605
TI  - Ulex europaeus I and glycine max bind to the human olfactory bulb.
AB  - The distribution of binding sites for the fucose-selective lectin Ulex europaeus
      I and the terminal N-acetylgalactosamine-selective lectin glycine max in the
      human olfactory bulb were studied. These lectins bound to primary olfactory axons
      in the olfactory nerve layer and the glomerular layer. They also bound to fibers
      located in the deeper layers such as the external plexiform layer and the
      granular layer. Furthermore they projected to the olfactory stalk but not in the
      cerebrum. The deeper projections of the lectin binding fibers may affect the
      function of the olfactory bulb in humans.

PMID- 8152606
TI  - Adrenergic excitation of cutaneous nociceptors in chronically inflamed rats.
AB  - To probe the mechanisms underlying sympathetically maintained pain, the effects
      of lumbar sympathetic chain stimulation (SS) and close arterial injection of
      norepinephrine (NE) on cutaneous nociceptor activities were studied in adjuvant
      inflamed rats. Two to 28 weeks after adjuvant treatment, single nerve recordings
      of polymodal receptors from the saphenous nerve were performed. In treated rats
      but not in controls, SS and NE were excitatory in 35-40% of units. Yohimbine and
      CH-38083 blocked NE excitation, but prazosin did not. Our data show that chronic
      inflammation initiates circumstances in which alpha 2-adrenoceptor-mediated
      sympathetic activity excites some nociceptors.

PMID- 8152607
TI  - Microglia express the type 2 plasminogen activator inhibitor in the brain of
      control subjects and patients with Alzheimer's disease.
AB  - Localization of type 2 plasminogen activator inhibitor (PAI-2) was investigated
      immunohistochemically in postmortem brain tissue of control subjects and patients
      with Alzheimer's disease (AD). Both the mouse monoclonal and the goat polyclonal
      antibodies to PAI-2 stained microglia. Reactive microglia were stained more
      intensely than resting microglia. PAI-2 may regulate the plasminogen activators
      and plasmin system in lesions of AD. It is suggested that PAI-2 plays a role for
      cell migration and matrix breakdown as well as for aberrant neurite outgrowth in
      senile plaques where persistent microglial activation is observed.

PMID- 8152608
TI  - Colocalization of GABA and glycine in the rabbit oculomotor nucleus.
AB  - In the present study we examined the possible colocalization of the inhibitory
      neurotransmitters glycine and GABA in the oculomotor nucleus of the rabbit.
      Serial sections were processed alternately for glycine and GABA postembedding
      immuno-cytochemistry. Ultrastructural analysis revealed that all terminals that
      showed glycine-positive immunoreactivity were also GABA positive; up to 5% of the
      GABA-positive terminals were also glycine positive.

PMID- 8152609
TI  - Phasic loss of intercostal muscle activity occurring with rapid eye movements
      during REM sleep.
AB  - We tried to estimate the phasic motor inhibition occurring with rapid eye
      movements (REMs) during REM sleep in children by means of polysomnography. Phasic
      inhibition of intercostal muscle activity with REMs has been proved by averaging
      the integrated surface electromyograms in three children. The average latency
      from the onset of REMs to this inhibition was 38.0 ms, their average duration
      being 237.0 ms. We discussed the possibility that the REM-related phasic
      inhibition obtained here was involved in the brainstem-spinal cord inhibitory
      system functioning during REM sleep.

PMID- 8152610
TI  - The preoptic nucleus: the probable location of the circadian pacemaker of the
      hagfish, Eptatretus burgeri.
AB  - By recording the locomotor activity rhythm of hagfish, Eptatretus burgeri, in
      which surgical lesions of the preoptic nucleus (PON) were made, we searched for
      the location of the circadian pacemaker in the hypothalamus. The characteristic
      rhythms were lost in animals lacking the anterior part of the hypothalamus, which
      includes the PON. Cuts in front of the PON did not affect the rhythm, but cuts
      behind the PON caused the animals to loose their rhythms. Destruction of the PON
      with a high-frequency lesion generator also caused loss of rhythms. These
      findings indicate that the pacemaker may be located in the PON, which has
      retinofugal connections.

PMID- 8152611
TI  - FMRF-amide modulates the electrical activity of the leech Retzius cell.
AB  - The effect of the peptide FMRF-amide on the electrical activity of the leech
      Retzius (R) cell was investigated using electrophysiological techniques. FMRF
      amide and six structurally related analogs increased the excitability of the R
      cell in several distinct ways that could act in concert to modulate transmitter
      release. 'Puffs' of FMRF-amide transiently depolarized the cell leading to a
      barrage of action potentials. This depolarization was followed by a phase of
      rhythmical bursting that appeared intrinsic to the neuron. FMRF-amide also
      broadened the plateau of the Ca(2+)-dependent action potential. The results
      suggest that the terminal Phe and Arg as well as the C-terminal amide are
      critical for the activity of these peptides.

PMID- 8152612
TI  - The effect of pergolide and MDL 72974 on rat brain CuZn superoxide dismutase.
AB  - It has previously been shown that both the dopamine receptor agonist, pergolide,
      and the monoamine oxidase inhibitor, (-)-deprenyl, can cause induction of CuZn
      superoxide dismutase in the rat striatum. We have now confirmed this effect of
      pergolide (0.04 mg/kg i.p.) as being localised to the striatum, but not the
      cerebellum, and shown it to take 3 weeks to develop. Furthermore, we have found
      that MDL 72974, a more specific monoamine oxidase inhibitor than (-)-deprenyl,
      failed to bring about such an induction either at a low selective monoamine
      oxidase B inhibitory dose, or at a higher non-selective dose.

PMID- 8152613
TI  - Immunohistochemical localization of transforming growth factor-alpha in choroid
      plexus of the rat and chicken.
AB  - Transforming growth factor-alpha (TGF-alpha) is a polypeptide which binds to
      epidermal growth factor-receptor (EGF-R) to carry out its function. We have
      observed strong TGF-alpha immunoreactivity in the developing and adult choroid
      plexus of the rat and chicken and glial cells of adult rats, by using a well
      characterized monoclonal antibody and the peroxidase method. Preabsortion of the
      antibody with the peptide gave negative staining. Since previous studies have
      shown that EGF-R is localized in several brain regions, but not in the choroid
      plexus, during development and adulthood, it is suggested that TGF-alpha,
      synthesized in the choroid plexus and transferred to the cerebrospinal fluid, has
      a role in brain development. TGF-alpha immunoreactivity found in glial cells, but
      not in neurons of adult rats, suggests that TGF-alpha in adulthood is also
      synthetized in the glial cell compartment.

PMID- 8152614
TI  - Effect of ipsilateral lesioning of the nucleus basalis magnocellularis and of L
      alpha-glyceryl phosphorylcholine treatment on choline acetyltransferase and
      acetylcholinesterase in the rat fronto-parietal cortex.
AB  - The present study assesses the effect of unilateral lesions of the nucleus
      basalis magnocellularis (NBM) and of treatment with L-alpha-glyceryl
      phosphorylcholine (GFC, choline alfoscerate) on the acetylcholine-synthesizing
      (choline acetyltransferase (ChAT)), and acetylcholine-degradating
      (acetylcholinesterase (AChE)) enzymes in the rat fronto-parietal cortex
      ipsilateral to the lesion. Ibotenic acid injections in the right NBM area caused
      a significant decrease of both ChAT and AChE activities as well as of
      histochemically reactive stores of AChE in the right fronto-parietal cortex.
      Treatment with GFC restored in part the loss of ChAT and AChE activities.
      Moreover, AChE reactivity is restored in the fronto-parietal cortex of NBM
      lesioned rats treated with GFC. GFC is a precursor in the biosynthesis of brain
      phospholipids which increases the bioavailability of acetylcholine in the nervous
      tissue. The possible relevance of the restoration of the marker enzymes of
      cholinergic neurotransmission by GFC in an animal model of cholinergic
      hypofunction is considered.

PMID- 8152615
TI  - Adenosine 5'-triphosphate modulation of nitrobenzylthioinosine binding sites in
      plasma membranes of bovine chromaffin cells.
AB  - Nitrobenzylthioinosine (NBTI) is a high affinity probe for facilitated diffusion
      nucleoside transporters. Kinetic analysis of the binding of [3H]NBTI to plasma
      membranes of chromaffin cells was conducted in the presence or absence of
      adenosine 5'-triphosphate (ATP). Similar curvilinear plots with a Hill number of
      1.32 were obtained in both conditions. ATP significantly increased the number of
      NBTI binding sites in these preparations showing Bmax values of 1.62 +/- 0.20
      pmol/mg protein for controls and 3.22 +/- 0.31 pmol/mg protein in the presence of
      ATP. However, the affinity constant (KD) was not significantly modified. The non
      metabolizable ATP analogue, 5'-adenylyl imidodiphosphate (AMP-PNP) and
      diadenosine tetraphosphate (Ap4A) can mimic the stimulatory ATP effect, but
      adenosine monophosphate (AMP) has no effect on the NBTI binding to plasma
      membranes. These results indicate a modulatory role for ATP, non-hydrolysis
      dependent, on nucleoside transport in chromaffin cells. Therefore, a nucleotide
      binding site on the nucleoside transporter similar to that described for glucose
      transporter could be suggested.

PMID- 8152616
TI  - Gonadotropin-releasing hormone, a neuropeptide of efferent projections to the
      teleost retina induces light-adaptive spinule formation on horizontal cell
      dendrites in dark-adapted preparations kept in vitro.
AB  - The teleost retina receives efferent projections from neurons of the nucleus
      olfactoretinalis at the base of the olfactory bulbs. These fibres contain
      gonadotropin-releasing hormone (GnRH) immunoreactive material and are presynaptic
      to retinal dopaminergic interplexiform cells. We have incubated isolated dark
      adapted retinae and eyecup preparations of roach with salmon-GnRH and found an
      increase in horizontal cell spinule numbers to 70% light-adaptive levels. This
      effect was blocked by addition of haloperidol to the incubation medium suggesting
      that GnRH acts via stimulation of the dopaminergic interplexiform cells. We
      conclude that GnRH containing efferent fibres are capable of inducing light
      adaptive changes in the retina and discuss their implication in the control of
      endogenous rhythms.

PMID- 8152617
TI  - What intracranial tissues in humans contain sumatriptan-sensitive serotonin 5-HT1
      type receptors?
AB  - We investigated the presence of sumatriptan-sensitive serotonin (5-HT)1 receptors
      in different human tissues by using a radioligand-binding technique with [3H]5
      HT. Sumatriptan displaced [3H]5-HT from frontal cortical and striatal membranes
      in a biphasic manner, with a high-affinity site corresponding to binding to the 5
      HT1D receptor. In blood platelet membranes, sumatriptan displaced [3H]5-HT with a
      100-fold lower affinity. Sumatriptan failed to displace [3H]5-HT in membranes
      from large cerebral arteries, pial vessels, coronary arteries and dura mater.
      These findings suggest that either there are no sumatriptan-sensitive 5-HT1
      receptors on intracranial blood vessels or they are so small in number that they
      cannot be detected by the radioligand-binding technique. Other mechanisms,
      possibly centrally mediated, may be responsible for the antimigraine action of
      sumatriptan.

PMID- 8152618
TI  - Effects of ozone exposure during pregnancy on ontogeny of sleep in rats.
AB  - Few studies regarding the effects of ozone exposure in the central nervous system
      (CNS), during the early stages of development have been reported. The study of
      sleep on newborn rats represents a model to understand the effects of this gas on
      the CNS. We studied the sleep organization in rats whose mothers were exposed to
      1 part per million (ppm) ozone during pregnancy. We found severe sleep
      disturbances such as a decrease in paradoxical sleep duration and inversion of
      the light-dark cycle or a circadian phase-shift of vigilance states. These
      results suggest that ozone exposure during pregnancy may affect the generating
      mechanisms of paradoxical sleep, and the regulation of circadian rhythms in rats.

PMID- 8152619
TI  - Ethanol inhibits the uptake of exogenous norepinephrine from the extracellular
      space of the rat cerebellum.
AB  - Rapid chronoamperometric recordings using nafion-coated carbon fiber electrodes
      coupled with pressure-ejection of drugs were used to investigate the effects of
      ethanol on norepinephrine (NE)-containing nerve terminals in the urethane
      anesthetized Fischer 344 rat. Local application of ethanol from a double-barrel
      micropipette did not produce detectable changes in extracellular levels of NE in
      the rat cerebellar cortex. However, when ethanol was applied prior to local
      application of NE, it was seen to inhibit the uptake of NE from the extracellular
      space. These results were compared to the effects seen from the local application
      of a known high-affinity uptake inhibitor, nomifensine. Nomifensine was found to
      inhibit the extracellular uptake of NE in rat cerebeller cortex similar to
      ethanol. Our results support the hypothesis that one effect of ethanol on the
      noradrenergic system of the rat cerebellum is an alteration in the uptake of NE
      into NE-containing nerve endings. In addition, the present data concerning
      ethanol-induced inhibition of NE clearance or uptake support our previous
      electrophysiological studies in which we found that ethanol can potentiate the
      modulatory effects of beta-agonists on GABA responses of cerebellar Purkinje
      neurons.

PMID- 8152620
TI  - Corticotropin-releasing factor in the locus coeruleus mediates EEG activation
      associated with hypotensive stress.
AB  - Although corticotropin-releasing factor (CRF) is thought to act as a
      neurotransmitter to activate the locus coeruleus (LC) during hypotensive stress,
      the consequences of LC activation by CRF are unknown. In the present study a
      hypotensive challenge that activated rat LC neurons also produced cortical
      electroencephalographic (EEG) correlates of arousal. Selective, bilateral LC
      inactivation by local clonidine infusion prevented EEG activation associated with
      hypotension. Additionally, bilateral LC infusion of CRF antagonists prevented
      both LC and EEG activation by this challenge. These results indicate that CRF,
      acting as a neurotransmitter to activate LC during stress, has a powerful of
      modulatory influence over global forebrain electrophysiological activity.

PMID- 8152621
TI  - Transient projections from rat occipital cortex are able to respond to a spinal
      target derived diffusible factor in vitro.
AB  - Layer V pyramidal neurons in the occipital part of the rat cerebral cortex
      project to both the cervical spinal cord and the tectum early in postnatal
      development. The occipito-spinal projection is transient and is subsequently
      withdrawn, while a permanent connection is maintained with the tectum. The
      withdrawal of the transient occipital corticospinal axons may be due to their
      inability to respond to target-derived influences. In the current study we co
      cultured explants of the occipital cortex and cervical spinal gray matter or
      tectum in 3-D collagen gels. Directional growth of the cortical axons towards
      either the cervical spinal gray or tectal explant was observed. This indicates
      that the failure of neurons located in the occipital cortex to maintain
      collaterals within the spinal cord in vivo is not due to their inability to
      respond to a target-derived factor, but must be regulated by other extrinsic
      factors.

PMID- 8152622
TI  - Global ischemia can cause DNA fragmentation indicative of apoptosis in rat brain.
AB  - Laddered DNA indicative of apoptosis was observed in the CA1 layer of hippocampus
      and in dorsolateral striatum following a global cerebral ischemic insult produced
      by transient two vessel occlusion in rats. The extent of this DNA damage was
      proportional to the duration of the ischemic episode. Breaks in DNA were
      demonstrated in situ in sections from post-ischemic brain in neurons of the
      hippocampal CA1 which undergo selective neuronal death but not in other cell
      types. It is concluded that there is an apoptotic component to selective neuronal
      death following global ischemia in rat brain.

PMID- 8152623
TI  - Differential effects of ethanol on the firing rates of Golgi-like neurons and
      Purkinje neurons in cerebellar slices in vitro.
AB  - Previous studies have demonstrated that ethanol (EtOH) inhibits the firing rate
      of Purkinje neurons both in vitro and in vivo. However, little is known about the
      response of cerebellar interneurons to EtOH. In this report, we describe the
      effects of locally applied EtOH on the firing of one type of cerebellar
      interneuron, tentatively identified as Golgi neurons, and on Purkinje cells in
      brain slices in vitro. The Golgi neurons were excited by EtOH, whereas EtOH
      depressed the firing rate of Purkinje neurons. To the best of our knowledge, this
      is the first report of responses of cerebellar Golgi neurons to local
      applications of EtOH.

PMID- 8152624
TI  - Nerve growth factor induces sensitivity to botulinum neurotoxin type A in
      norepinephrine-secreting PC12 cells.
AB  - Inhibition of Ca(2+)-activated norepinephrine secretion by the botulinum
      neurotoxin (NT) serotypes A and E was examined in permeabilized PC12 cells. The
      dichain type E NT reduced with dithiothreitol (DTT) completely inhibited
      secretion whereas the dichain type A NT reduced with DTT exhibited incomplete
      inhibitory activity. In contrast, Ca(2+)-activated secretion in PC12 cells
      treated with nerve growth factor (NGF) was completely inhibited by reduced type A
      NT. The NGF-treated PC12 cells retained a sensitivity to the type E NT similar to
      that of untreated PC12 cells. These results indicate that the intracellular
      mechanisms of inhibition of the types E and A NTs are distinct. NGF appears to
      either induce the expression of a component selectively required for type A NT
      sensitivity, or otherwise modifies the secretory apparatus to acquire type A NT
      sensitivity.

PMID- 8152625
TI  - Breaking the cycle of disadvantage: a nursing system of health care.

PMID- 8152626
TI  - Unlicensed personnel no cure for an ailing health care system.

PMID- 8152627
TI  - Managed competition and critical issues facing nurses.

PMID- 8152628
TI  - Health care reform: will nursing respond?

PMID- 8152629
TI  - Attention, attention must be paid!

PMID- 8152630
TI  - Building partnerships in health care: creating whole systems change.

PMID- 8152631
TI  - Rhetoric and reasoning on assisted suicide--an exchange of views.

PMID- 8152633
TI  - New approach to NCLEX.

PMID- 8152632
TI  - AIDS: advocacy & activism: we need money and services now!

PMID- 8152634
TI  - Feminism not the cause of society's devaluing of nursing.

PMID- 8152635
TI  - Participation in professional organizations is part of professional nursing.

PMID- 8152636
TI  - Computerized Clinical Simulation Testing: its use for competence assessment in
      nursing.

PMID- 8152637
TI  - Preferred learning style and educational technology: linear vs. interactive
      video.

PMID- 8152638
TI  - The Educational Technology Network (E.T.NET).

PMID- 8152639
TI  - Editorial peer review: is nursing at risk?

PMID- 8152640
TI  - A taxonomy of pediatric primary care nursing interventions.

PMID- 8152641
TI  - President's message: a call for public hearings on physician control of health
      care.

PMID- 8152642
TI  - Financial problems and solutions for the nurse executive.

PMID- 8152643
TI  - The prospective pricing system using the diagnosis related group (DRG) case mix
      measure and the nurse executive.

PMID- 8152644
TI  - Keepers of the keys: economics, ethics, and nursing administrators.

PMID- 8152645
TI  - The cost and quality of patient outcomes: a look at managed competition.

PMID- 8152646
TI  - Collaboration: the CNE-CFO connection.

PMID- 8152647
TI  - Tools and techniques to effect budget neutrality.

PMID- 8152648
TI  - Resource allocation in health care: an example from the United Kingdom.

PMID- 8152649
TI  - Managing the costs of nursing care delivery.

PMID- 8152650
TI  - The evolution of financial systems, from accounting to EISs. Executive
      Information System.

PMID- 8152651
TI  - International nursing administrative research.

PMID- 8152652
TI  - Teaching strategies for operationalizing nursing's agenda for healthcare reform.
AB  - Nursing's Agenda for Healthcare Reform presents a vision and specific suggestions
      for the future of nursing. Changes proposed by the agenda challenge nursing
      educators to prepare new practitioners to deliver healthcare in community
      settings. The authors offer specific means for nursing educators to provide
      students with clinical experiences that are consistent with the agenda. These
      experiences include practice in primary-care settings and case management, and
      more effective health promotion activities.

PMID- 8152653
TI  - Preparing students psychologically for the NCLEX-RN.
AB  - Years of experience in school and healthcare environments do not lessen the fear
      and anxiety associated with taking a written examination, especially one that
      will determine whether you will be allowed to practice as a professional nurse.
      The author discusses an approach to increase students' test performance on the
      NCLEX-RN examination.

PMID- 8152654
TI  - A collaborative work study program between nursing service and education.
AB  - A work study program allows students to gain academic credit while earning a
      salary for the nursing services they render. At the same time, they gain
      additional experience to increase clinical competence. The program can also serve
      as a recruiting device for the employing healthcare agency. The authors describe
      a specific work study program developed between a nursing department in a large
      urban medical center and a university nursing program.

PMID- 8152655
TI  - Reciprocal learning in the clinical area.

PMID- 8152656
TI  - Issues in designing an RN-MS track.
AB  - The combined RN-MS track is a streamlined pathway to the masters degree in
      nursing, particularly appealing to nurses who are highly motivated and have their
      career goals firmly in place. The author discusses issues in developing and
      implementing this track and presents initial evaluations.

PMID- 8152657
TI  - Operating room learning.

PMID- 8152658
TI  - Using a gaming-simulation to teach students how to collect data and make clinical
      judgments.

PMID- 8152660
TI  - Group verbal development of care plans: a post clinical conference strategy.

PMID- 8152659
TI  - A quick screening assessment tool for students.

PMID- 8152661
TI  - Advancing nursing in the academic community: adopt an administrator.
AB  - The role of faculty in nursing schools is unique. Faculty members belong to the
      community of scholars, as well as the community of practitioners. The authors
      describe a program to educate key university leaders about the role of nursing
      faculty. The program achieved its objectives in a timely, cost-effective manner,
      and could be easily replicated at other universities.

PMID- 8152662
TI  - Using opioids with nonopioids.

PMID- 8152663
TI  - How to share unit equipment safely.

PMID- 8152664
TI  - Assessing a carotid pulse.

PMID- 8152665
TI  - Keeping track of intake and output.

PMID- 8152666
TI  - Measuring antinuclear antibodies.

PMID- 8152667
TI  - Are you ready for a code?

PMID- 8152668
TI  - Patient-teaching aid. Avoiding trouble with allergy drugs.

PMID- 8152669
TI  - Her husband was dying and she wanted to watch the code.

PMID- 8152670
TI  - A snapshot look at intensive care units.

PMID- 8152671
TI  - S.I.A.D.H.

PMID- 8152672
TI  - Hypovolemic shock: is your patient at risk?

PMID- 8152673
TI  - Euthanasia: in support of patients.

PMID- 8152674
TI  - Avoiding hypoglycemia.

PMID- 8152675
TI  - Septic shock: can you recognize the clues?

PMID- 8152676
TI  - Preprinted order forms: 7 tips for troubleshooting.

PMID- 8152677
TI  - Health care trends that will reshape nursing.

PMID- 8152678
TI  - Nurse's guide to identifying cardiac rhythms.

PMID- 8152679
TI  - Supporting each other.

PMID- 8152680
TI  - Understanding your patient's denial.

PMID- 8152681
TI  - Mrs. Hill needed more than caring ... and more than a care plan.

PMID- 8152682
TI  - Self-test. Caring for acutely ill patients.

PMID- 8152683
TI  - Myths & facts ... about older adults.

PMID- 8152684
TI  - Assessing a rapid heart rate.

PMID- 8152685
TI  - H.I.V. disease. Nursing attitudes.

PMID- 8152686
TI  - A promise to Billie.

PMID- 8152687
TI  - Lower gastrointestinal motility.

PMID- 8152688
TI  - Benign myocardial uptake of hydroxymethylene diphosphonate.
AB  - During 'routine' bone scanning with diphosphonates, 10 elderly men were noted to
      show prominent myocardial uptake of Tc-hydroxymethylene diphosphonate (HDP)
      consistently, but no heart activity was seen with Tc-methylene disphosphonate
      (MDP). None had evidence of recent myocardial injury and the uptake persisted
      over a period of many months. In some, myocardial uptake defects were noted,
      analogous to 201Tl- and Tc-methoxyisobutyl isonitrile (MIBI) scans
      postinfarction. The condition appears to be essentially benign but its aetiology
      remains obscure. We have not been able to identify its cause; presumably
      atherosclerosis is one factor.

PMID- 8152689
TI  - Structural perturbations of monoclonal antibodies following radiolabelling: in
      vitro evaluation of different techniques.
AB  - Antibodies are labelled routinely with direct labelling techniques in which some
      of the native disulphide groups are reduced to sulphydryls. Using polyacrylamide
      gel electrophoresis (PAGE) as an analytical tool and human polyclonal IgG (HIgG)
      labelled with 99Tcm by the ascorbic acid (AA), stannous chloride (SnCl2) and 2
      mercaptoethanol (2-ME) techniques, we have quantitatively determined any
      fragmentation of the protein and the radioactivity associated with fragments.
      HIgG labelled with 99Tcm by two bifunctional chelating agents provided the vital
      comparison. The results indicated that in the bifunctional chelating agent (BFCA)
      methods 65 and 61% of the activity was associated with protein with an apparent
      molecular weight of 150,000 D. The corresponding numbers for the AA, SnCl2 and 2
      ME methods were 46.4, 21 and 3.9%. With 2-ME, 96% of the activity was associated
      with low molecular weight fragments. Although monoclonal antibody fragmentation
      may not affect immunoreactivity of the protein, it may influence biodistribution.

PMID- 8152690
TI  - Bone marrow scintigraphy in small cell carcinoma of the lung.
AB  - A comparative study of bone marrow scintigraphy using 99Tcm-nanocolloid,
      conventional bone scintigraphy and bone marrow biopsy were performed in 35
      patients with histologically proven small cell carcinoma of the lung to determine
      whether bone marrow scintigraphy has a role in the early detection of bone marrow
      metastases. The sensitivity, specificity and accuracy for detection of metastases
      were 100, 92 and 94%, respectively, in bone marrow scintigraphy, 91, 88 and 89%,
      respectively, in bone scintigraphy, and 50, 100 and 86%, respectively in bone
      marrow biopsy. This study confirmed that bone marrow scintigraphy is a useful
      technique for the detection of early metastases. Bone marrow scintigraphy is also
      suggested as the first choice examination in clinical practice for diagnosis of
      metastases in small cell carcinoma of the lung.

PMID- 8152691
TI  - Dosimetric assessment of radiolabelled lipiodol as a potential therapeutic agent
      in colorectal liver metastases using combined CT and SPECT.
AB  - Lipiodol has previously been used as an agent for targeted radiotherapy by
      selective retention in primary hepatic tumours following direct hepatic arterial
      infusion. We have considered the potential dosimetry of 131I-labelled lipiodol in
      treating colorectal liver metastases. Fifteen patients with multiple colorectal
      liver metastases underwent selective hepatic angiography when 5 ml lipiodol
      labelled with 40 MBq 131I were infused. All patients underwent planar
      scintigraphy of the abdomen and thorax, single photon emission computed
      tomography (SPECT) of the liver and whole body counting on at least two occasions
      following lipiodol injection. Computed tomographic (CT) images of the liver were
      also taken typically 7 days postinjection. The lipiodol was found to deposit on
      the periphery of metastases of less than 10 cm diameter. In one patient a
      metastasis of diameter greater than 15 cm failed to infuse. In two patients the
      lobe of the liver containing metastases was not successfully infused. Overlay of
      CT and SPECT images confirmed concentration in metastases. Quantification of
      SPECT images indicated that between 55 and 100% (median 86%) of the injected
      activity was retained in the liver following injection, and tumour to liver
      ratios of dose delivered ranged from 1.21:1 to 4.7:1 (median 3.1:1). Tumour does
      ranged from 11.8 to 43.3 mGy MBq-1 injected. Dose to the lungs ranged from 0 to
      46% of the liver dose (median 16%). Lipiodol has potential for treatment of
      colorectal liver metastases in targeted radiotherapy.

PMID- 8152692
TI  - Tumour affinity of 203Pb-chloride: comparison with 67Ga-citrate and 201Tl
      chloride.
AB  - The radionuclide 203Pb decays completely by electron capture to stable 203Tl with
      a half-life of 52 h. The primary radiation from the decay is gamma-ray radiation
      280 keV (80%). 203Pb is produced easily from the natural metal thallium by the
      method described below. 203Pb-chloride is a promising imaging agent for tumour
      scanning because of the large retention value for tumour tissue and the small
      value for normal organs, but the large value for the kidney and bone is a
      shortcoming when considering it as an imaging agent. The retention value of 203Pb
      in tumour tissue is larger than that of 201Tl and smaller than that of 67Ga. The
      tumour/inflammatory lesion retention ratio for 203Pb is very large in comparison
      with those for 67Ga and 201Tl. 203Pb accumulates to a large extent in viable
      tumour tissue, and less in necrotic tumour tissue and in inflammatory lesion.
      Therefore, 203Pb-chloride is far better for visualization of viable tumour tissue
      than 67Ga and 201Tl if the large retention values for the kidney and bone were
      reduced.

PMID- 8152693
TI  - The role of nuclear cardiology in hypertension.
AB  - In view of the increased risk of cardiac events in systemic hypertension,
      particularly in patients with left ventricular hypertrophy, it is important to
      have reliable methods of assessing cardiac structure and function and myocardial
      perfusion in these patients. While echocardiography is the noninvasive method of
      choice for measuring the severity of left ventricular hypertrophy there is no
      alternative at present to invasive coronary angiography to define accurately
      coronary artery anatomy. Nuclear cardiological investigations are extremely
      useful in the assessment of systolic and diastolic function at rest and during
      exercise. Furthermore, myocardial perfusion imaging is of value in identifying
      myocardial ischaemia and assessing the functional importance of coronary artery
      lesions. Recent studies have also suggested that nuclear cardiology
      investigations may be the best way to identify nonfunctioning but viable areas of
      the myocardium which may benefit from revascularization.

PMID- 8152694
TI  - Oral cholecystography compared to cholescintigraphy for evaluation of cystic duct
      patency prior to ESWL treatment.
AB  - In a prospective, blinded study of 109 patients with cholecystolithiasis, oral
      cholecystography and 99Tcm-EHIDA cholescintigraphy were compared in terms of
      reliability for demonstrating cystic duct patency: one of the prerequisites for
      extracorporeal shock wave lithotripsy (ESWL) treatment of cholecystolithiasis.
      Patients with a positive result on one or both tests were regarded as having
      cystic duct patency. Patients with negative and uncertain result of both tests or
      one of each were regarded as having no cystic duct patency. Concordance between
      the two tests was obtained in 93 of 109 patients. The diagnostic reliability of
      cholescintigraphy and oral cholecystography were 95 and 86%, respectively (P <
      0.05), suggesting a more precise determination of gallbladder filling with
      scintigraphy.

PMID- 8152695
TI  - 99Tcm-labelled anti-fibrin Fab' fragment for evaluating the course of venous
      thrombosis in the rabbit.
AB  - Immunoscintigraphy was performed using the Fab' fragment of 99Tcm-labelled T2G1s
      anti-fibrin monoclonal antibody in a rabbit experimental model of venous
      thrombosis of known and increasing age (1, 3 and 7 days). Scans were positive in
      3/7 cases for 1-day thrombosis (fibrin-poor network) and in 7/7 cases for 3-day
      thrombosis (fibrin-rich network). In rabbits with 7-day thrombosis, the scan was
      positive (2/4 cases) only when connective tissue was not present in the clot.
      Scintigraphic results were concordant with those of biodistribution studies
      showing the mean percentage of injected dose per gram 99Tcm-T2G1s present in the
      thrombosed vein wall (0.043, 0.082 and 0.07 for thrombi at 1, 3 and 7 days,
      respectively). Mean thrombosed vein wall-to-blood ratios were 1.027, 2.291 and
      1.301, respectively. Immunoscintigraphy with T2G1s anti-fibrin monoclonal
      antibody thus enabled hematological status to be evaluated.

PMID- 8152696
TI  - Question of the month--September 1993. 133Xe and lung ventilation imaging.

PMID- 8152697
TI  - Quality control of radionuclide calibrators.

PMID- 8152698
TI  - Cerebral blood flow in individuals before and after a high-altitude Himalayan
      expedition.

PMID- 8152699
TI  - Modelling the integration of myocardial regional perfusion and function.
AB  - The purpose of the study is to describe a method for the investigation of
      myocardial kinetics (wall motion or wall thickening) to define myocardial
      perfusion characteristics further. The data are myocardial perfusion single
      photon emission computed tomographic images gated in eight time bins, following
      the administration of a 99Tcm-labelled perfusion agent. Wall motion is defined by
      the phase and amplitude of the centripetal motion of the first moment of the
      myocardial count rate density distribution along a radius originating in the
      centre of the left ventricular cavity. Wall thickening is defined by phase and
      amplitude of the changes in the second moment of the density distribution along
      the radius multiplied by the maximum density. Wall motion amplitude was abnormal
      in 28% of transient and 43% of fixed perfusion abnormalities, phase delays were
      present in 28 and 57%, respectively. Wall thickening was abnormal in amplitude in
      14% of transient and 86% of fixed perfusion abnormalities. We conclude that the
      positive predictive value of wall-thickening abnormalities relative to fixed
      perfusion abnormalities is high (86%). Whether fixed perfusion defects with
      normal wall thickening represent viable myocardium remains to be investigated.

PMID- 8152700
TI  - AIDS update.

PMID- 8152701
TI  - Restoration of occupational capacity in post-cardiac patients.
AB  - Employees returning to work after injury and illness have typically been offered
      an 'all or nothing' approach to rehabilitation. Dr Bruce Davies questions this
      attitude and argues for improved policies to facilitate a more effective return
      to work for post-cardiac patients.

PMID- 8152702
TI  - Promoting wellness in an OH setting.
AB  - The opportunity to educate employees about wellness concepts presents itself in a
      variety of settings. Benita Ramsarran and Sharon Wilson use the background of a
      vaccination clinic as an example in which to maximise learning opportunities.

PMID- 8152703
TI  - Laboratory animal allergy: an employer's responsibility.
AB  - Allergies in animal laboratory workers are a significant occupational health
      hazard. Karen Taylor and Frank Hardiman describe how this problem has been
      tackled at the Maudsley Hospital.

PMID- 8152704
TI  - OH: labour's agenda. Interview by Helen Kogan.

PMID- 8152705
TI  - Pre-employment medicals: some legal issues.

PMID- 8152706
TI  - Seafarers' HIV/AIDS education package.

PMID- 8152707
TI  - Sewage workers and hepatitis A.

PMID- 8152708
TI  - The UKCC: open to debate?. Interview by Helen Kogan.

PMID- 8152709
TI  - Reproductive hazards in the workplace.

PMID- 8152710
TI  - OH nursing in the EC: education, training and practice.

PMID- 8152711
TI  - HIV in perspective.

PMID- 8152712
TI  - Planning for the ageing workforce.
AB  - A changing and ageing workforce will influence how occupational health services
      are organised in the future. Lorraine Ashton describes demographic trends
      affecting the labour market.

PMID- 8152713
TI  - The effects of non respiratory exposure to substances.
AB  - Contact dermatitis can be avoided but still features prominently in compensation
      claims. Christopher Packham and Ray Russell-Fell argue that control of non
      respiratory substances should be given greater attention by those responsible for
      workplace health and safety.

PMID- 8152715
TI  - Fundamentals of research.

PMID- 8152714
TI  - Working together in Europe.
AB  - With the recent formation of the Federation of Occupational Health Nurses within
      the European Community (FOHNEC) there is now hope for closer cooperation between
      European OHNs. Frances Baker, UK delegate to the Federation, describes events
      leading to its formation and outlines its aims.

PMID- 8152716
TI  - A new look at COSHH.

PMID- 8152717
TI  - What are the current guidelines for working with nursing technicians, nursing
      assistants and other unlicensed assistive personnel?

PMID- 8152718
TI  - Linda's cholecystectomy--safe and comfortable.

PMID- 8152719
TI  - A president ponders on collective bargaining.

PMID- 8152720
TI  - Balancing the demands in your life through humor (continuing education credit).

PMID- 8152721
TI  - The centenarian: key to longevity.

PMID- 8152722
TI  - [The spatial-temporal organization of the extracellular matrix].
AB  - Data on composition and structure of extracellular matrix (ECM) of different
      tissues and at different developmental stages are summarized. ECM secreted by
      cells is a complex supermolecular structure formed of polymerized collagen,
      elastin, proteoglycans, and structural glycoproteins. Its organization varies
      depending on tissue type or on location within the same tissue. Variation of ECM
      composition is determined by qualitative and quantitative differences in
      combination of its constituent components, as well as by microheterogeneity of
      these components. Permanent feed-back exists between cells and ECM. Morphological
      and functional relationships are established between basal membranes, ECM,
      pericellular matrix, and cytoskeleton. An important role in these relationships
      belongs to integrins, a family of transmembrane proteins specifically interacting
      with ECM components. ECM composition specifically changes during development and
      regeneration, correlating with differentiation and morphogenesis of corresponding
      tissues. Thus, ECM has a complex structure, is responsible, to a certain extent,
      for tissue specificity and for stage-specific differences between tissues, and
      can be regarded as a probable position information carrier, both in embryos and
      adult animals.

PMID- 8152723
TI  - [The embryotoxic effect in rats exposed to the blood serum of newborn infants
      tested for the presence of transfer factors].
AB  - Pregnant rats (day 14 of gestation) received intraamniotic injections of newborn
      human serum. Transfer factors (TF) present in injected serum produced significant
      embryotoxic and teratogenic effects, as well as changes in coordination of motor
      activity (EMG) in newborn rats. The extent of embryological disturbances and the
      motor activity of 33- to 34-day old recipient rats depend on TF concentration (at
      serum dilution 1:2) and on the state of infant's motor functions ("normal" group
      and "risk" group). The results obtained allow to objectively determine the
      pathogenic effect of serum TF on embryotoxicity and formation of motor
      coordination in the donor infant.

PMID- 8152724
TI  - [The preimplantation embryonic development of 2 species of mammals from the
      family Mustelidae (Mustela erminea and Mustela vison)].
AB  - The preimplantation development of common weasel and American mink embryos was
      studied using light microscopy. Oocytes and blastomeres of these embryos are rich
      with lipids synthesized during oogenesis. Apparently, most lipids are utilized
      during the trophoblast formation. Large spherical blastomeres protecting zona
      pellucida are formed by the stage of implantation. The shape of the blastocyst,
      as well as central superficial implantation, are typical for carnivores and
      distinguish the studied order from other ones (e.g., from rodents or
      artiodactyls). Several aspects of evolution of mammals are discussed. A
      suggestion is made that differences between orders in the shape of the blastocyst
      and ways of their implantation reflect poly-phyletic origin of mammals.

PMID- 8152725
TI  - [The interphotoreceptor matrix: its development, composition and functional
      importance].
AB  - Published data on studies of interphotoreceptor matrix (IPM) of the vertebrate
      eye are reviewed. Particular attention is paid to the formation of IPM, its
      chemical composition, and its role in normal functioning of the retina.

PMID- 8152726
TI  - [The search for the DNA sequences characterizing the granulocytic lineage of cell
      differentiation in the HL-60 line].
AB  - cDNA of HL-60 cells induced to differentiation into granulocytes was hybridized
      with the excess of mRNA of K 562 cells induced to differentiation into
      erythrocytes. Cloning of cDNA sequences characterizing the induced
      differentiation of HL-60 cells into granulocytes was performed. The clones
      obtained were shown to contain sequences encoding a zinc finger motif, which is
      specific for DNA-binding domain of protein activators of transcription.

PMID- 8152727
TI  - Update of the subconjunctival THC:YAG (holmium) laser sclerostomy ab externo
      clinical trial: 30-month report.
AB  - A THC:YAG laser (thulium, holmium, chromium-doped YAG crystal) was used to create
      93 thermal sclerostomies ab externo in 81 glaucomatous eyes of 76 patients. Pulse
      energies of 80 to 120 mJ were used, with a repetition rate of 5 pulses per
      second. Total energy levels to produce full-thickness sclerostomies ranged from
      1.4 to 7.2 J. Estimated probability of success was 0.66 at 12 months and 0.57 up
      to 30 months. The mean intraocular pressure in the successful cases was 12.8 +/-
      4.0 mm Hg.

PMID- 8152728
TI  - Adjunctive use of transconjunctival mitomycin-C in ab externo diode laser
      sclerostomy surgery in rabbits.
AB  - This study evaluates the role of transconjunctival mitomycin-C (MMC) in laser
      sclerostomy surgery. Sixteen albino rabbits underwent ab externo diode laser
      sclerostomy surgery in one eye (with the fellow eye as a control), with a single,
      intraoperative, 7-minute transconjunctival application of MMC (MMC group). Ten
      rabbits had the same sclerostomy surgery without MMC (NOMMC group). Successful
      filtration, defined as a difference in intraocular pressure less than 4 mm Hg
      between the operative and control eyes, lasted significantly longer in the MMC
      group (16.4 +/- 11.0 days) than in the NOMMC group (8.5 +/- 4.5 days) (P = .02).
      These data suggest that transconjunctival MMC can enhance the success of diode
      laser sclerostomy surgery in rabbits.

PMID- 8152729
TI  - Subconjunctival THC:YAG laser sclerostomy under a partial-thickness corneal flap.
AB  - To evaluate the safety and effectiveness of THC:YAG laser sclerostomy in reducing
      intraocular pressure (IOP), we performed 16 subconjunctival sclerostomies under a
      partial-thickness corneal flap. We report the 3- and 6-month follow-up results in
      these patients, all of whom had intractable glaucoma resistant to previous
      surgical treatment. The mean IOP decreased from a pretreatment value of 30 mm Hg
      to a posttreatment value of 14 mm Hg at 3 months. Fifty-seven percent of the
      treated eyes achieved an IOP below 20 mm Hg at 6 months. A significant reduction
      in glaucoma medications is also reported among the successes. Complications were
      minimal.

PMID- 8152730
TI  - Hydroexpression of subluxated lenses using a glide.
AB  - During the past 8 years, 15 patients (20 eyes) underwent a variety of operations
      to remove a subluxated lens. In six of these eyes, a new technique, featuring an
      anterior chamber maintainer and a plastic glide, was used for intracapsular
      cataract extraction (ICCE). The results achieved in these eyes were compared with
      those in 8 eyes in which cryo extraction was used, in 1 in which pars plana
      lensectomy was used, in 4 in which aspiration of lens material and peeling of the
      capsule was used, and in 1 in which a viscoelastic material and spatula were
      used. Using the glide, the lens is extracted through a scleral tunnel incision or
      a limbal opening. The length of the opening is somewhat smaller than the diameter
      of the lens and is significantly smaller than that used in traditional ICCE. The
      visual outcomes achieved with these various techniques were essentially
      identical. The proposed technique is simple and relatively safe for these
      complicated cases.

PMID- 8152731
TI  - Cryotherapy for retinopathy of prematurity: a histopathologic comparison of a
      treated and untreated eye.
AB  - A female infant born at 28 weeks gestational age, weighing 570 g, developed
      retinopathy of prematurity (ROP) which progressed to threshold disease in one
      eye. Transscleral cryotherapy of the avascular peripheral retina resulted in
      complete clinical regression of the active ROP in that eye. The fellow eye
      continued to manifest subthreshold ROP. Histopathologic findings included a
      striking reduction of the cryotreated retina to a thin glial scar, with
      associated retinal pigment epithelium atrophy, denudation of Bruch's membrane,
      and extensive atrophy of the underlying choroidal vasculature, predominantly the
      choriocapillaris.

PMID- 8152732
TI  - Normal eyelid crease position in children.
AB  - Proportions of the upper lid were determined based on the following measurements
      in 33 children: lash-line-lid crease (LC), lashline-lower brow (LB), vertical
      fissure, and horizontal fissure. Age-matched mean measurements (mean LC/LB ratio
      = 0.33) for 26 white vs 7 black children, and for 16 males vs 17 females were not
      significantly different. However, the mean ratio in 15 preschool and school-age
      children was significantly greater than that in 18 infants and toddlers (less
      than 4 years old) (P < .01). We conclude that the normal eyelid crease position
      in children is one third up the lashline to the lower brow. However, the normal
      eyelid crease position in infants and toddlers is slightly less than, and, in
      older preschool and school-age children, slightly greater than this distance up
      the lashline. Thus, age may determine the surgical placement of the eyelid crease
      in children with indistinct creases.

PMID- 8152733
TI  - Laser indirect ophthalmoscope photocoagulation in an incubator for the treatment
      of retinopathy of prematurity.
AB  - Argon blue-green or diode laser indirect ophthalmoscope photocoagulation,
      performed through the transparent wall of an incubator, was used to treat
      threshold retinopathy of prematurity in two premature infants who were in poor
      systemic condition and could not be treated out of the incubator. Despite
      technical difficulties posed in one or both cases by their lateral position,
      small pupils, persistent tunica vasculosa lentis, and hazy cornea, there were no
      systemic complications and the retinopathy regressed in both cases.

PMID- 8152734
TI  - The use of subconjunctivally administered tissue plasminogen activator after
      trabeculectomy.
AB  - Blockage of aqueous flow in the early postoperative period can be devastating to
      the success of trabeculectomy. We used tissue plasminogen activator (tPA)
      subconjunctivally in an attempt to release a trabeculectomy flap that appeared to
      be adherent to its scleral bed. No change was noted 90 minutes after injection,
      but a highly elevated bleb was present on the first postoperative day.
      Subconjunctivally administered tPA may be useful in releasing the fibrin "glue"
      in cases with adherent trabeculectomy flaps.

PMID- 8152735
TI  - Evaluation of a tapered, blunt, bipolar cautery tip for trabeculectomy.
AB  - A bipolar cautery instrument with a tapered, blunt tip has been developed for
      glaucoma filtering surgery. Evaluated in 30 consecutive trabeculectomy
      procedures, the instrument proved suitable for all aspects of the operation. The
      narrow, 23-gauge shaft and tapered, blunt tip allowed gentle, pin-point
      coagulation of individual bleeders, as well as cauterization of tracks of tissue
      in a continuous motion. The unit was effective for external cauterization of
      conjunctival and scleral vessels, as well as for internal cauterization of
      anterior uveal tissue.

PMID- 8152736
TI  - A modification of cryosurgery for the management of elevated bleb.
AB  - Elevated blebs may be very troublesome to patients, especially those with only
      one eye. I describe a technique that can be used to reduce the size of the bleb
      without diminishing its function, and, as in the case presented, resolve corneal
      dellen.

PMID- 8152737
TI  - How physicians can best help the public and themselves.

PMID- 8152738
TI  - Methylcellulose for gonioscopy.

PMID- 8152739
TI  - Delayed onset of sympathetic ophthalmia.

PMID- 8152740
TI  - Hans Goldmann.

PMID- 8152741
TI  - Effect of depth upon the smoothness of excimer laser corneal ablation.
AB  - The Argon Fluoride (ArF) Excimer laser is currently used for experimental
      reshaping of the front surface of the cornea for the correction of myopic
      refractive error (photorefractive keratectomy, PRK) and for smoothing corneal
      irregularities (phototherapeutic keratectomy, PTK). Both PRK and PTK are in FDA
      clinical trials, but are more readily available outside the U.S.A. These
      techniques have achieved reasonable success in spite of early reports that deeper
      ablation procedures can cause reduced corneal clarity (haze) or a result which is
      less accurate or tends to regress. We studied how different depths of excimer
      tissue removal affect the smoothness of the ablation zone of the rabbit cornea.
      Dutch belted rabbits were immediately sacrificed by pentobarbital overdose. Their
      corneas were de-epithelialized with a knife or by the excimer laser and then were
      photoablated. A 4.5-mm circular ablation beam was delivered to each denuded area,
      but the beam was masked by positioning a steel blade to partially block the laser
      beam, thus creating variable ablation depths corresponding to 0.0, 12.5, 37.5,
      and 62.5 microns. The eyes were fixed in situ by topical and anterior chamber
      application of glutaraldehyde and the corneas were excised after 5 min and placed
      in glutaraldehyde for tissue processing. The corneas were whole-mounted and
      examined by scanning electron microscopy (SEM). The resultant micrographs show
      increasing irregularity of the ablated surface as a function of depth. The
      irregularity appeared to be due largely to the inhomogeneities of the anterior
      stroma, which is known to be layered by alternately directed collagen
      fibrils.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152742
TI  - Effect of corneal edema upon the smoothness of excimer laser ablation.
AB  - We studied the effect of corneal hydration upon ablation rate in excimer laser
      photorefractive keratectomy (PRK). This variable may alter the subepithelial
      smoothness and the resulting clarity of the result. The eyes of freshly
      slaughtered pigs (N = 5) and the eyes of Dutch-belted rabbits (N = 4) (in vivo)
      were de-epithelialized and central ablation zones 3.0 to 4.5 mm in diameter were
      produced in the subepithelial corneal layers using a 193 nm argon fluoride (ArF)
      ophthalmic excimer laser. Ablation was performed immediately or after a 15-min
      incubation period in distilled water as a means of inducing corneal edema.
      Smoothness was evaluated using specular reflection microscopy and showed the
      water-treated surface to be increasingly less regular than the nonwater-treated
      samples. Water treatment may affect the final outcome of the PRK procedure and
      indicates the need to monitor the preoperative cornea for the development of any
      edema, especially after the epithelium is removed.

PMID- 8152743
TI  - Depth of field of plus lenses and reading telescopes.
AB  - Using simple optical equations we solved for the depth of field (or range of
      movement for clear viewing) of plus lenses and near telescopes of the same
      equivalent power and then compared them. The prevalent clinical wisdom states
      that reading telescopes have a smaller depth of field than plus lenses. Our
      results show depth of field to be equal for both and inversely proportional to
      the square of the equivalent power. A simple nomograph of depth of field vs.
      power has been prepared for clinicians to use.

PMID- 8152744
TI  - Photoreceptor orientation in iris coloboma.
AB  - PURPOSE: Investigate photoreceptor orientation and alignment in an observer with
      a simple coloboma of the iris and no retinal involvement. METHOD: Using a
      psychophysical procedure, extensive measurements of the Stiles-Crawford functions
      of the first kind (SCE I) were obtained from this observer. RESULTS: In this
      observer, the usual center-of-the-exit-pupil-of-the-eye alignment tendency of
      photoreceptors (inferred from the peaks of the SCE I functions) is absent. The
      inferred orientation of photoreceptors at numerous retinal loci tested lies
      outside the pupil, opposite the direction of the downwardly displaced pupil
      center. CONCLUSIONS: These results add support to previous suggestions that
      nonphototropic forces such as retinal tractional forces should be considered as
      an integral part of the mechanism(s) subserving human photoreceptor alignment in
      both normal and anomalous observers.

PMID- 8152745
TI  - The family of sunlight-related eye diseases.
AB  - Five ocular disorders, independent clinical entities affecting different parts of
      the eye with distinctive histopathological features, are part of the same family
      of eye diseases because they share the same causal factors, of which the most
      important is molecular damage produced by sunlight. This family of eye diseases
      includes the major sources of impaired vision and blindness in our society, age
      related cataract and age-related macular degeneration. Pterygium, photokeratitis,
      and cancer of peri-ocular skin are also sunlight-related eye diseases. In each
      condition, solar radiation, oxygen, and heat, acting in combination, are the
      primary causal factors. Analysis of the action spectra indicates that only the
      high-energy radiation in the solar spectrum, particularly the ultraviolet (UV),
      is hazardous to the eye. The evidence in support of these conclusions is
      summarized. It indicates that the risk of all sunlight-related eye diseases can
      be diminished by use of eyewear that absorbs the high-energy constituents of
      solar radiation during exposure to sunlight.

PMID- 8152746
TI  - Coordinate systems and vector spaces for lenses.

PMID- 8152747
TI  - Defining the scope of practice of optometry.
AB  - Defining the scope of practice of optometry is difficult, but important for the
      profession and optometric education. Even though the scope of practice can be
      defined in various ways and is constantly changing, the schools and colleges of
      optometry must have some sense of the boundaries of the profession in order to
      develop educational programs which will prepare students to practice well into
      the future. The use of three-dimensional diagrammatic models creates a visual
      representation of the elements which define the scope of practice. Additionally,
      these models can assist schools and colleges to improve their understanding of
      the various dynamics which must be considered in developing the most appropriate
      methods to analyze the competencies required for entry into the practice of
      optometry.

PMID- 8152748
TI  - The critical difference: scope of optometry practice vs. entry level competency.
AB  - This paper proposes a survey-based approach on how optometry can define the
      critical difference in competency levels between entry level and experienced
      practitioners. The report describes the design and pilot testing of a survey
      instrument on clinical competencies. This work is still in an early stage, and
      these preliminary findings are meant to encourage other individuals to work on
      empirical models for defining entry level clinical competencies. The pilot study
      concludes that a full scale project to describe empirically the entry level
      competencies for optometrists is feasible and worthy of effort. The findings of a
      descriptive study can help gauge at an institutional or national level what is
      the extent and diversity of views about what constitutes entry level clinical
      competencies for optometry.

PMID- 8152749
TI  - Education for entry level competency: teaching strategies.
AB  - The goal of this discussion is to summarize the results of the Workshop on
      Teaching Strategies that was held as part of the Curriculum Conference at Denver,
      Colorado in July, 1992. Various teaching methods were presented as alternatives
      to traditional lectures and laboratories; among these problem-based learning
      (PBL) was the subject of greatest interest. Advantages and disadvantages
      encountered using PBL in optometric education were presented. The need for a more
      uniform core curriculum among optometric institutions is emphasized, as well as
      the need for appropriately trained faculty to teach in the newer curricular
      areas.

PMID- 8152750
TI  - Optometric education: planning for the future.
AB  - Collectively, the American Optometric Association (AOA) and the Association of
      Schools and Colleges (ASCO) have felt a growing need to develop a strategic plan
      that would ensure that the financial and other resource needs of the educational
      establishment can and will be met. Only when this is accomplished can the
      profession of optometry continue to be able to meet the needs of the public. An
      initial Georgetown Conference--Summit on Optometric Education was held in March
      1992. It was followed later in 1992 by a Conference on the Scope of Optometric
      Practice and a Curriculum Conference. Scheduled for 1993 were four additional
      conferences which dealt with Optometric Students, Optometric Research, Graduate
      Education, Residencies and Fellowships, and the Financing of Optometric
      Education. Critical questions have been addressed and recommendations have been
      made. Additional efforts are underway to reach the stated objectives of the
      initial conference.

PMID- 8152751
TI  - Comparison of clinical diagnostic tests in hydrogel extended wear.
AB  - We compared the relative value of biomicroscopy, pachometry, esthesiometry, and
      corneal oxygen flux measurements for the detection of corneal hypoxia in myopic
      patients wearing hydrogel extended wear lenses. Measurements were standardized by
      relating the change in each parameter to its test-retest reliability. After 3
      months of extended wear the greatest change occurred in biomicroscopic signs
      (microcysts and vacuoles, fluorescein staining, inferior conjunctival hyperemia)
      and in stromal edema measured with pachometry. These four signs were poorly
      correlated to each other (Pearson's r < 0.3), indicating that none could be
      considered redundant. Stromal striae, endothelial edema (blebs), esthesiometry,
      and corneal oxygen flux measurements showed relatively little change during the
      period of lens wear.

PMID- 8152752
TI  - Hypothyroidism and glaucoma.

PMID- 8152753
TI  - Interferon treatment of SRNV.

PMID- 8152755
TI  - No jump balls in journal editing.

PMID- 8152754
TI  - IOLs in uveitis patients.

PMID- 8152756
TI  - Risk factors for the development of encapsulated filtering blebs. The role of
      surgical glove powder and 5-fluorouracil.
AB  - PURPOSE: To study risk factors for the development of encapsulated filtering
      bleb, especially the effect of surgical glove powder and 5-fluorouracil on the
      development of encapsulated blebs. METHODS: One hundred forty-eight patients who
      underwent trabeculectomy were prospectively studied. After patient of each
      surgeon were divided into two subgroups of 5-fluorouracil versus no 5
      fluorouracil, each subgroup was then randomized for powder versus powder-free
      surgical gloves. All patients were followed for at least 2 months (mean, 3.5
      months; range, 2-10 months). RESULTS: The overall incidence of encapsulated bleb
      was 11.2% when an encapsulated bleb was defined by clinical characteristics with
      a peak intraocular pressure of 26 mmHg or higher. The group that received 5
      fluorouracil had a lower incidence of encapsulated blebs despite a higher rate of
      previous surgeries, whereas the group with powdered gloves had increased
      incidence. The subgroup in which powder-free gloves were used in conjunction with
      postoperative injections of 5-fluorouracil had the lowest incidence of
      encapsulated blebs (2.6%) compared with the other subgroups (12.0%-17.9%) (P =
      0.01). CONCLUSION: Combined use of powder-free surgical gloves and 5-fluorouracil
      may reduce the incidence of encapsulated bleb.

PMID- 8152757
TI  - Reconstruction of filtering blebs with free conjunctival autografts.
AB  - BACKGROUND: Situations arise in which the surgical repair or revision of
      filtering blebs is either technically impossible or inadequate, and total
      reconstruction becomes necessary. This is most frequently encountered in eyes
      that have undergone multiple procedures, resulting in significant bulbar
      conjunctival scarring and episcleral fibrosis. METHODS: To preserve the pre
      existing filtration site, the authors successfully treated five such patients in
      whom conjunctival scarring adjacent to and surrounding the blebs precluded local
      revision, by transplanting free conjunctival autografts. Two patients required
      grafting from the fellow eye. Specific modifications from previously reported
      conjunctival flap techniques were used to enhance graft healing and continued
      filtration. RESULTS: Satisfactory intraocular pressure control was maintained in
      all patients receiving minimal to no anti-glaucomatous medications with an
      average follow-up of 42.6 months (range, 7-90 months). No patient had a
      significant decrease in visual acuity or surgical complications. CONCLUSION: Free
      conjunctival autografting techniques are a useful adjunct in the surgical
      revision of leaking, failed, or migrating filtration blebs.

PMID- 8152758
TI  - Initial clinical experience with the baerveldt implant in complicated glaucomas.
AB  - BACKGROUND: The Baerveldt glaucoma implant is an aqueous shunting device with a
      large surface area that is installed through a conjunctival incision in one
      quadrant of the eye. This study presents the initial results of the first 13
      patients who underwent Baerveldt implantation as part of the Food and Drug
      Administration approval process. METHODS: Thirteen patients with medically
      uncontrollable complicated glaucomas underwent one-stage implantation of either a
      200- or 350-mm2 Baerveldt implant without postoperative systemic antifibrosis
      therapy. Surgical success was defined as intraocular pressure greater than or
      equal to 6 and less than or equal to 21 mmHg without glaucoma reoperation or
      devastating complication. RESULTS: Eight patients (62%) had successful surgical
      outcomes, with a mean follow-up of 17.3 +/- 7.0 months (+/- standard deviation)
      (range, 6-24 months). Seven (70%) of the ten patients with glaucomas associated
      with aphakia or pseudophakia had successful outcomes, whereas only one (50%) of
      the two patients with neovascular glaucomas had a successful outcome. One patient
      with glaucoma associated with nanophthalmos and an unsuccessful filtering
      procedure had a failed outcome. The postoperative visual acuities remained within
      one line of the preoperative visual acuities or improved in 62% of the patients.
      The most frequent complications among all patients were transient serous
      choroidal effusion (23%) and hyphema (15%). CONCLUSION: Initial results of the
      Baerveldt implant generally are comparable with other implants. It is easier to
      install and requires less extensive conjunctival dissection than other large
      implants. Additional studies are needed to evaluate the effectiveness of the
      Baerveldt implant in affording long-term intraocular pressure control.

PMID- 8152759
TI  - Krupin eye valve with disk for filtration surgery. The Krupin Eye Valve Filtering
      Surgery Study Group.
AB  - PURPOSE: The authors evaluate a long posterior tube shunt device with a pressure
      sensitive valve for filtration surgery in eyes with recalcitrant glaucoma.
      METHODS: The device consisted of an anterior chamber tube connected to an oval
      (13 x 18 mm) episcleral explant. The explant was designed to maximize the area of
      surrounding encapsulation while still allowing implantation within one quadrant.
      A pressure-sensitive and unidirectional slit valve in the tube provided
      resistance to aqueous humor flow. One-stage implantation without the use of
      restrictive sutures was performed in 50 eyes with various types of glaucoma
      unresponsive to prior glaucoma surgery. RESULTS: Mean (+/- standard error of the
      mean) preoperative intraocular pressure (IOP) of 36.4 +/- 1.6 mmHg was reduced
      significantly (P < 0.001) to 8.3 +/- 1.3 mmHg on the first postoperative day.
      Mean anterior chamber depth (scale, 0-4+) was 3.4 +/- 0.1. Mean IOP 1 month after
      surgery was 14.1 +/- 1.3 mmHg. The implant was removed from four eyes due to IOP
      failure (1 eye), external erosion (2 eyes), or endophthalmitis (1 eye). A
      suprachoroidal hemorrhage occurred in one eye on the first postoperative day.
      Diplopia developed in one eye after surgery. Mean IOP at last follow-up
      examination (mean, 25.4 +/- 2.4 months; range, 16-36 months) was 13.1 +/- 1.3
      mmHg. Intraocular pressure was 19 mmHg or lower in 80% of the eyes, 59% of which
      were without adjunctive antiglaucoma medications. CONCLUSIONS: Design features of
      the Krupin Eye Valve with Disk result in a large area of encapsulation in a
      single ocular quadrant which functions as an external reservoir for passage of
      aqueous humor. The valve portion facilitates maintenance of anterior chamber
      depth during the early postoperative interval. This new therapeutic device can be
      effective in the long-term control of IOP in glaucomatous eyes not responsive to
      prior filtration surgery with adjunctive antimetabolite therapy.

PMID- 8152760
TI  - Dipivefrin reduces blood flow in the ciliary body in humans.
AB  - PURPOSE: Adrenergic substances are used widely for lowering intraocular pressure
      in the treatment of glaucoma. The hypothetic mechanisms for lowering the
      intraocular pressure by adrenergic drugs are decreased blood flow in the ciliary
      body and direct receptor-related reduction of aqueous humor production. The aim
      of this study is to measure noninvasively the blood flow in the anterior uvea in
      humans after topically administered dipivefrin. METHOD: The blood flow of iris
      and ciliary body was measured by laser Doppler flowmetry. Laser Doppler flowmetry
      blood flow and results of the electrocardiogram were simultaneously measured and
      stored over a period of 3 minutes. In the authors' setup, laser light was
      projected by a fiber optic transcorneally onto the iris or 2 mm transscerally
      from the limbus into the ciliary body. For improvement of the signal-to-noise
      ratio, a statistical averaging procedure was performed by averaging 100 sweeps of
      2 seconds of the digitalized laser Doppler flowmetry signals triggered by the R
      onset of the electrocardiogram (averaging laser Doppler flowmetry). Using this
      method, reproducible pulse curves of blood flow of iris and ciliary body were
      established with systolic maxima and diastolic minima. In a double-blind study
      design involving 33 young, healthy persons (mean age, 25 +/- 7 years), the effect
      of topically administered dipivefrin, naphazoline, and NaCl solution (0.9%) on
      the blood flow of iris and ciliary body was examined. RESULTS: Dipivefrin reduces
      significantly (average, 49%) the mean blood flow in the ciliary body. Naphazoline
      and NaCl solution do not change the blood flow in the ciliary body. Dipivefrin,
      naphazoline, and 0.9% NaCl show no significant effect on the iridal blood flow.
      CONCLUSION: The observed data suggest that dipivefrin decreases ciliary body
      blood flow.

PMID- 8152761
TI  - Rhegmatogenous retinal detachment after Molteno glaucoma implant surgery.
AB  - BACKGROUND: The Molteno implant is a device used for surgical treatment of
      complicated glaucoma. Rhegmatogenous retinal detachment (RD) is a relatively rare
      complication of Molteno implant surgery. This study was undertaken to evaluate
      the clinical features including the surgical management and postoperative outcome
      of patients with rhegmatogenous RD after Molteno implant surgery. METHODS: The
      authors reviewed 350 consecutive patients who had Molteno surgery and identified
      16 patients with subsequent rhegmatogenous RD. They also studied one patient
      referred for RD repair after Molteno surgery at another institution. RESULTS: The
      risk of rhegmatogenous RD was 5%. Seventy percent (12/17) of the patients
      presented within 4 months of the Molteno procedure. Dialysis and flap tear were
      the most common types of retinal break found. Forty-one percent (7/17) of the
      patients had proliferative vitreoretinopathy. In three patients, clinical
      features suggested RD resulting from the Molteno procedure. In other patients,
      previous ocular surgery and underlying ocular disease may have contributed to the
      development of RD. Retinal detachment repair was attempted in all patients. Among
      16 patients with at least 6 months of follow-up, 56% (9/16) had successful retina
      attachment. Forty-four percent (7/16) of the patients maintained formed vision.
      Eighteen percent (3/16) of the patients maintained visual acuity of at least
      20/40. Intractable glaucoma did not develop in any of the patients with an
      attached retina. Recurrent RD, endophthalmitis, cyclitic membrane, or intractable
      glaucoma led to phthisis bulbi or enucleation in 44% (7/16) of the patients.
      CONCLUSION: A combined approach by vitreoretinal and glaucoma surgeons can
      restore vision and maintain glaucoma control in patients with rhegmatogenous RD
      associated with Molteno implant surgery.

PMID- 8152762
TI  - Fibrinolytic-assisted removal of experimental subretinal hemorrhage within seven
      days reduces outer retinal degeneration.
AB  - PURPOSE: To better determine the surgical window for removing experimental
      subretinal hemorrhages in the cat model and to compare the histopathologic effect
      of such removal with the natural history of untreated subretinal hemorrhages.
      METHODS: Twenty-three large experimental subretinal hemorrhages were created with
      a neodymium:YAG laser focused through a performed retinal bleb in a cohort of
      cats. Fourteen subretinal hemorrhages were observed without treatment, six were
      removed at 7 days through a micropipette after injecting 10 micrograms/ml of
      human recombinant tissue plasminogen activator (rt-PA) into the subretinal space,
      and three were removed through an access retinotomy without the use of rt-PA. The
      tissues from these eyes were examined with light and electron microscopy 14 to 28
      days after creation of the subretinal hemorrhages. RESULTS: Severe outer retinal
      degeneration was evident by day 14 in all of the untreated subretinal hemorrhages
      3 disc diameters or greater in size. In contrast, the outer retinal architecture
      was better preserved in the eyes that underwent rt-PA-assisted removal of their
      subretinal hemorrhage that was 3 disc diameters or greater on day 7. In these
      eyes, mild abnormalities such as abnormally short and misaligned photoreceptor
      outer segments with vacuolization were present within the retina that was
      formerly located over the hemorrhage center. The eyes that underwent subretinal
      hemorrhage removal through an access retinotomy without rt-PA on day 7 had a low
      lying retinal detachment and outer retinal degeneration. CONCLUSION: Removing
      experimental subretinal hemorrhages within 7 days of their occurrence with the
      assistance of rt-PA and an ultramicrosurgical approach may reduce outer retinal
      degeneration in the cat model.

PMID- 8152763
TI  - Clinicopathologic correlation of a macular hole treated by cortical vitreous
      peeling and gas tamponade.
AB  - PURPOSE: To study the histopathology of a stage III macular hole that had been
      treated by vitrectomy with cortical vitreous and epicortical vitreous membrane
      peeling and gas tamponade. METHODS: The light and electron microscopic features
      of a treated macular hole were studied. RESULTS: A 16-microns-wide break was
      present in the external limiting membrane. This was sealed by Muller cell
      processes. Photoreceptors adjacent to the healed defect appeared normal. No
      cystoid macular edema was present. CONCLUSION: Cortical vitreous peeling and gas
      tamponade can allow the macular hole to settle and the edges to re-approximate.
      The residual defect can be sealed by Muller cells.

PMID- 8152764
TI  - Effect of methazolamide on chronic macular edema in patients with retinitis
      pigmentosa.
AB  - PURPOSE: To determine the effectiveness of methazolamide for improving visual
      acuity and macular edema in patients with retinitis pigmentosa. METHODS:
      Seventeen subjects with retinitis pigmentosa and chronic macular edema
      participated in a prospective, placebo-controlled, double-masked, crossover
      design study in which either methazolamide or a placebo was taken for 3 weeks.
      Visual acuity, fluorescein angiograms, and subjective impressions were obtained
      at baseline and after 3 weeks of treatment with each substance. A subgroup of
      subjects were enrolled in a more extended period of methazolamide treatment for
      an additional 3 months. RESULTS: Methazolamide resulted in the improvement of
      angiographic macular edema in 9 of 17 subjects. As a group, visual acuity
      statistically improved with methazolamide. However, improvement in at least one
      eye, of between two and four lines more than while taking placebo, occurred in
      only three (undilated pupils) or four (dilated pupils) subjects. Subjective
      improvement during treatment with methazolamide but not placebo occurred in only
      one subject. An extended period of methazolamide treatment for an additional 3
      months in a subgroup of patients did not result in additional beneficial effects
      on visual acuity. In fact, a partial rebound in the extent of macular edema was
      found. CONCLUSIONS: Although angiographic improvement of macular edema can occur
      in patients with retinitis pigmentosa treated with methazolamide, notable
      (between 3 and 4 lines) or even moderate (between 2 and 3 lines) visual acuity
      improvement was seen in relatively few patients. When methazolamide was
      administered in a placebo-controlled fashion, subjective improvement in visual
      function also was not readily apparent. A more substantial subjective improvement
      in visual function had occurred with the use of acetazolamide in five of six
      subjects who also had participated in a previous treatment trial with the use of
      acetazolamide.

PMID- 8152765
TI  - Erosive vitreoretinopathy. A new clinical entity.
AB  - PURPOSE: Vitreoretinopathies are disorders characterized by an abnormal vitreous
      gel structure and associated retinal changes. The authors report a pedigree with
      vitreous changes characteristic of the vitreoretinopathies, but with retinal
      pigment epithelial changes, electroretinographic abnormalities, and a clinical
      course distinct from previously described entities. METHODS: Twenty-six family
      members were examined. Complete ophthalmologic examinations, electroretinography,
      and perimetry were performed on patients who were at genetic risk for the
      disease. Particular attention was given to vitreous morphology and examination of
      the retinal and retinal pigment epithelium (RPE). RESULTS: Fifteen individuals
      affected with an autosomal dominant vitreoretinal degeneration were identified.
      The disease is characterized by nyctalopia, progressive visual field loss, marked
      vitreous syneresis, progressive RPE atrophy, and combined traction-rhegmatogenous
      retinal detachments (11 patients). Thinning or "erosion" of the RPE in younger
      patients permits increased visualization of the choroidal vessels. In advanced
      conditions, equatorial areas are seen that appear clinically devoid of RPE, with
      extensive posterior atrophy in older patients. Diffuse rod-cone dysfunction is
      demonstrated by electroretinography. High myopia, epiphyseal dysplasia, orofacial
      anomalies, and systemic manifestations characteristic of other
      vitreoretinopathies are not present. CONCLUSION: The authors describe an entity
      clinically distinct from other vitreoretinopathies. The disease is characterized
      by pronounced vitreous abnormalities, complicated retinal detachments, and a
      progressive pigmentary retinopathy. The most unusual and constant feature is the
      progressive change in RPE with concurrent visual field constriction and
      electroretinographic abnormalities. Because the RPE initially seems normal and
      progressively thins or "erodes" in the equatorial periphery, the descriptive name
      "erosive" vitreoretinopathy is proposed.

PMID- 8152766
TI  - Retinal necrosis in X-linked lymphoproliferative disease.
AB  - BACKGROUND: X-linked lymphoproliferative disease is a hereditary disease that
      renders the males susceptible to fatal infectious mononucleosis, aplastic anemia,
      malignant lymphoma, and hypogammaglobulinemia after infection by the Epstein-Barr
      virus. METHODS: The authors examined the clinical and pathologic findings in an 8
      year-old boy with bilateral retinal necrosis who died with aplastic anemia as a
      complication of X-linked lymphoproliferative disease. RESULTS: Results of
      histopathologic examination of the eyes disclosed retinal necrosis, and
      examination using the polymerase chain reaction technique showed Epstein-Barr
      virus genomic DNA in the left eye. CONCLUSION: Retinal necrosis may be part of
      the expanding spectrum of X-linked lymphoproliferative disease. It is unknown if
      the retinal necrosis is due directly to Epstein-Barr virus infection or a host
      inflammatory response.

PMID- 8152767
TI  - Natural history of indeterminate pigmented choroidal tumors.
AB  - PURPOSE: The purpose of this study is to delineate the natural history of
      indeterminate pigmented choroidal lesions and identify parameters from the
      initial visit that correlate with lesion enlargement. METHODS: The authors
      retrospectively reviewed the records of all patients with indeterminate pigmented
      choroidal lesions seen in consultation at the Ocular Oncology Unit at the
      University of California, San Francisco, after 1975. Clinical examination, fundus
      photography, fluorescein angiography, and ultrasound data were examined.
      Investigators masked to outcome coded sequential parameters of each of these
      modalities. Data were analyzed using both univariate and multivariate censored
      data techniques. RESULTS: Of 293 lesions, 98 grew. The 5-year actuarial rate of
      growth was 36%. Greater tumor thickness, presence of symptoms, orange pigment,
      internal quiet zone on B-scan, and hot spots on fluorescein angiography all were
      significant predictors of tumor enlargement (relative risk of detectable tumor
      growth, > 1.8). Risk scores were calculated, and subsets with higher probability
      of future growth were identified. In five of the patients with growing lesions,
      metastatic disease developed after a median posttreatment follow-up period of 51
      months. CONCLUSION: Most small indeterminate pigmented lesions can be followed
      safely by serial observation and ancillary testing. The authors identified models
      based on data from the initial visit that can be used as an adjunct to planning
      tumor management.

PMID- 8152768
TI  - Microcirculation architecture of melanocytic nevi and malignant melanomas of the
      ciliary body and choroid. A comparative histopathologic and ultrastructural
      study.
AB  - PURPOSE: This study was designed to (1) describe the vascular patterns of ciliary
      body and choroidal nevi by light microscopy, (2) compare the vascular
      ultrastructure of nevi with vessels of the normal uvea and uveal melanomas, and
      (3) compare the behavior of ciliochoroidal melanomas with and without a nevus
      like vascular architecture. METHODS: After delineating the vascular patterns of
      23 choroidal and ciliary body nevi by light microscopy, the authors identified 49
      melanomas that had the same vascular patterns as nevi from a previously published
      series of 234 uveal melanomas. The survival of these 49 patients who had
      melanomas with a nevus-like vascular architecture was compared with the 185
      patients who had melanomas that lacked this vascular profile. RESULTS: By light
      microscopy, the only vascular patterns identified in nevi are "normal" vessels,
      zones of avascularity ("silent" pattern), straight, and parallel vessels; closed
      vascular loops and networks were not detected in nevi. By transmission electron
      microscopy, the vascular basement membrane of malignant melanomas was
      multilaminar, fragmented, and significantly thicker than in normal eyes or nevi.
      None of the patients with nevi died of metastatic disease. Fourteen percent of
      patients whose melanomas had the same vascular profile as nevi died of metastatic
      disease, whereas 32% of patients whose melanomas had vascular patterns other than
      those seen in nevi died of metastatic melanoma (P = 0.012). CONCLUSIONS: The
      microcirculation architecture marks tumor progression in uveal melanocytic
      lesions by light and electron microscopy. In the spectrum of these lesions, nevi
      are benign, melanomas that have the same vascular profile as nevi have an
      intermediate biologic behavior, and melanomas with vascular networks are strongly
      associated with death due to metastatic disease.

PMID- 8152769
TI  - Evaluation of laser flare-cell photometry in the appraisal and management of
      intraocular inflammation in uveitis.
AB  - BACKGROUND: Laser flare-cell photometry enables objective and quantitative
      measurement of anterior chamber inflammation. Systematic data currently are used
      mainly for clinical research; few are yet available in uveitis. The authors
      prospectively studied the amount, duration, and pattern of inflammation for well
      defined uveitic conditions and evaluated the potential usefulness of laser flare
      cell photometry in uveitis. METHODS: Mean initial flare was calculated in HLA-B27
      positive acute anterior uveitis, acute herpes zoster uveitis, acute retinal
      necrosis (ARN), Fuchs heterochromic cyclitis, intermediate uveitis (pars planitis
      type), posterior sarcoidosis, posterior pole toxoplasmosis, and birdshot
      chorioretinopathy. Evolution of aqueous flare and cells was analyzed for acute
      anterior uveitis, ARN, and pars planitis treated for cystoid macular edema (CME),
      all of which received a standardized therapy. RESULTS: Blood-aqueous barrier
      disruption was very pronounced in acute anterior uveitis (170.2 +/- 33
      photons/msecond), ARN (177.4 +/- 88 photons/msecond), moderate in posterior
      sarcoidosis (38.1 +/- 11 photons/msecond), acute zoster uveitis (25.8 +/- 6.1
      photons/msecond), and pars planitis (19.1 +/- 2.9 photons/msecond) but only
      minimal in Fuchs heterochromic cyclitis (10.2 +/- 3.5 photons/msecond),
      toxoplasmosis (9.0 +/- 1.2 photons/msecond) and birdshot chorioretinopathy (5.7
      +/- 1.1 photons/msecond). For acute anterior uveitis, ARN, and pars planitis with
      CME, the inflammatory patterns were determined. The potential of laser flare-cell
      photometry for precise follow-up and adjustment of therapy was illustrated in
      cases of anterior and posterior uveitis. CONCLUSION: The authors' findings show
      that laser flare-cell photometry allows quantitative assessment of inflammation
      in uveitis and contributes to improved management of patients with uveitis.

PMID- 8152770
TI  - A combined incision technique of radial keratotomy. A comparison to centripetal
      and centrifugal incision techniques in human donor eyes.
AB  - PURPOSE: To evaluate and compare the extent of corneal flattening and the anatomy
      of the incision grooves produced by centrifugal, centripetal, and combined
      incisions in a human donor eye model. METHODS: Twenty-seven eyes, divided into
      three groups of nine, received eight-incision radial keratotomy using the
      centrifugal, centripetal, or combined incision technique. Corneal curvature was
      evaluated using a topography system, and the anatomy of the incision was assessed
      by light microscopy and scanning electron microscopy. RESULTS: The average
      central corneal flattening at the 3-mm clear zone was 4.16 +/- 1.47 diopters (D)
      for centrifugal incisions; 7.71 +/- 2.77 D for centripetal incisions; and 9.26 +/
      1.75 D for combined incisions. The difference in corneal flattening between eyes
      that received centrifugal versus either centripetal or combined incisions was
      significant (P < 0.01), whereas the difference between combined and centripetal
      incisions was not significant (P = 0.174). Anatomic differences were observed
      within the incision grooves produced by the three techniques. CONCLUSION: The
      authors describe a novel combined incision technique of radial keratotomy that
      provides the potential safety of a centrifugal incision with the effect of a
      centripetal incision.

PMID- 8152771
TI  - Pterygium recurrence time.
AB  - PURPOSE: To define the amount of time necessary to follow patients after
      pterygium removal to identify a recurrence. METHODS: The authors reviewed
      patients who supposedly had a recurrence of their pterygium and analyzed the
      records to determine the duration of these recurrences. RESULTS: One hundred
      sixty-one known pterygium recurrences were identified from records. Those
      patients with frequent follow-up in whom recurrence could be determined to within
      1 month were in group A, and those in whom the time of recurrence was indefinite
      were in group B. For patients in group A, there was an average time to the first
      recurrence of 123 +/- 113 days, with second and third recurrences at 97 +/- 58
      and 67 +/- 47 days, respectively. Survival curve analysis showed that there was a
      50% chance that there would be a recurrence within the first 120 days, and there
      was a 97% chance there would be a recurrence within 12 months of its removal.
      CONCLUSION: This suggests that a 1-year follow-up time is likely to identify a
      recurrence.

PMID- 8152772
TI  - The use of low-dose mitomycin C for prevention of recurrent pterygium.
AB  - BACKGROUND: The administration of high doses of topical mitomycin C after
      pterygium excision causes a variety of complications. METHODS: Seventy-five
      patients who had advanced or recurrent pterygia underwent excision of pterygia,
      leaving the sclera bare. Patients were randomized in a masked fashion into three
      groups of 25 patients each. Patients in group 1 received topical 0.01% mitomycin
      C for 5 days, patients in group 2 received 0.02% mitomycin C for 5 days, and
      those in group 3 were treated with 1200 rad beta-irradiation. Patients were
      followed by a surgeon who was masked to the patient treatment. The mean follow-up
      period was 15.3 months. RESULTS: The recurrence rate after pterygium surgeries
      was 8% in group 1, 4% in group 2, and 20% in group 3. There were no statistical
      differences between the study groups. Delay of epithelialization for 8 weeks in
      one patient and degenerative calcification of conjunctiva 18 months after surgery
      in another patient, both from group 2, were the only complications in this study.
      CONCLUSION: This study indicates the advantage of 0.01% mitomycin C for post
      operative prevention of recurrence of pterygium.

PMID- 8152773
TI  - Orbital dermoid cysts located within the lateral rectus muscle.
AB  - BACKGROUND: Two patients, a 13-year-old girl and a 31-year-old man, had an
      orbital dermoid tumor located in the lateral rectus muscle. This unusual location
      of dermoid tumors has not been reported previously. METHODS: Computed tomography
      and magnetic resonance imaging showed a cystic mass within the belly of the
      lateral rectus in each patient. Surgical excision through a lateral orbitotomy
      showed a well-circumscribed mass surrounded by lateral rectus fibers. No
      periorbital attachment was noted. RESULTS: Results of histopathologic evaluations
      showed a dermoid cyst. Postoperatively, the diplopia and proptosis resolved. In
      one patient, an unusual subconjunctival deposition of fat droplets was seen.
      CONCLUSION: The findings in patients demonstrate an unusual presentation of
      dermoid cysts and make an addition to the differential diagnosis of enlarged
      extraocular muscles.

PMID- 8152774
TI  - The silent sinus syndrome. A cause of spontaneous enophthalmos.
AB  - PURPOSE: Spontaneous enophthalmos and hypoglobus, in the absence of other
      symptoms and unrelated to trauma or surgery, may be alarming to both physician
      and patient. The authors describe the clinicopathologic features of a benign
      syndrome ("silent sinus syndrome") with this constellation of features and
      discuss the possible pathophysiology. METHODS: A multicenter retrospective search
      for similar clinical cases was performed. All clinical records, computed
      tomographs, and pathology reports for each case were reviewed at one center. A
      literature search for similar cases also was conducted. RESULTS: Nineteen cases
      of a new syndrome are presented. This syndrome affects individuals at
      approximately the fourth decade of life (average age, 36 years; range, 29-46
      years); is characterized by bone resorption and remodeling of the orbital floor
      due to otherwise asymptomatic maxillary sinus disease; is associated with
      ipsilateral maxillary sinus hypoplasia; and is not fully explained by any
      previously described, classic cystic lesion of the maxillary antrum. CONCLUSION:
      Enophthalmos and hypoglobus unassociated with prior trauma, surgery, or other
      symptoms may represent "silent sinus syndrome," which is ipsilateral maxillary
      sinus hypoplasia and orbital floor resorption.

PMID- 8152775
TI  - Nonarteritic ischemic optic neuropathy. The impact of tobacco use.
AB  - BACKGROUND: Numerous associations to anatomic variation and systemic vascular
      disease have been made to anterior ischemic optic neuropathy (AION) but exogenous
      agents have not been emphasized. The authors studied the effect that smoking had
      in the development of AION. The relevance of other intraocular and systemic
      vascular disease to AION also is discussed. METHODS: Over a 10-year period
      (January 1980-May 1990), nonarteritic AION was diagnosed in 148 patients, 137 of
      whom were included in this analysis. FINDINGS: Of the 137 patients identified
      with nonarteritic AION, 28 smokers were statistically younger, at 51 years of
      age, compared with 83 nonsmokers whose mean age was 64 years (P = 0.005).
      CONCLUSIONS: Cigarette smoking is an important risk factor in the development of
      AION. Cessation of smoking appears to reduce the risk of AION to that of the
      nonsmoking population.

PMID- 8152776
TI  - The use of botulinum toxin for treatment of acquired nystagmus and oscillopsia.
AB  - PURPOSE: To evaluate the role of botulinum toxin A (BTA) in treating patients
      with diminished visual acuity secondary to acquired nystagmus and oscillopsia.
      METHODS: Twelve patients with acquired nystagmus causing oscillopsia and reduced
      vision were treated with injection of BTA. Botulinum toxin A was injected
      directly into the horizontal recti in three patients, and in nine patients
      retrobulbar BTA was administered. Injections were given at 3- to 4-month
      intervals and repeated as long as patients noted improvement in their quality of
      life. RESULTS: Improvement in visual function varied, and not all patients
      benefited from the procedure. However, 8 of 12 patients demonstrated a measurable
      improvement in visual acuity. Transient ptosis was the most common side effect.
      CONCLUSION: Retrobulbar BTA provides a simple and safe alternative in managing a
      condition for which alternative treatments are typically unsatisfactory.

PMID- 8152778
TI  - Funding company loans to the practitioner and monthly financial statements.

PMID- 8152777
TI  - Marginal discrepancy as related to margin design in porcelain-fused-to-Dicor
      restorations.

PMID- 8152779
TI  - Economics of laser dentistry.

PMID- 8152781
TI  - Did Dr. Acer murder his patients?

PMID- 8152780
TI  - Dental skeletal rehabilitation.

PMID- 8152782
TI  - Dental implants: the blade implant.

PMID- 8152783
TI  - The "claspring": a new adjunct to removable appliance therapy.

PMID- 8152784
TI  - [Significance of skin manifestations in current medical diagnosis].
AB  - Skin lesions may signify not only cutaneous diseases, but also pathological
      changes of inner organs or standing of systemic diseases. The cutaneous symptoms
      characteristically associated with internal diseases are known as dermatodromes.
      The author analyzes the general impact of these on up-to-date medical diagnostic
      work, with special regard to their unique role in the early diagnosis of many
      important organic diseases, as well as to their significance for disease
      prognosis and therapy.

PMID- 8152785
TI  - [Long-term results of total colectomy insuring restoration of continence].
AB  - The early postoperative and long term results of 4 acute (3 toxic megacolon, 1
      life threatening bleeding from colon diverticulitis) and 32 elective (16 colitis
      ulcerosa, 10 familiar polyposis, 4 diffuse Crohn disease, 2 total colon
      diverticulosis) total colectomies and continence reconstruction has been
      discussed. In the acute cases the continence has been restored in two steps with
      Kock reservoir, or with immediate ileorectostomy. In the elective cases the
      continence was ensured with 16 ileoanal anostomies and pouch formation (4 "S" and
      12 "J" pouch), 12 ileorectostomies and two Kock reservoir, the operation has been
      finished only in 2 cases, with definitive Brooke type ileostomy. The operative
      lethality was 4/1 and 32/1, the serious postoperative complication rate 4/2 and
      32/5 respectively. The long term results of 11 pouch operations and 13
      ileorectostomies are discussed. A whole continence were achieved on 11/9 and
      13/12 patients respectively. The nocturnal soiling and daily defecation frequency
      was 75% and 25% higher and the whole rehabilitation time was twice so long after
      pouch operation then after ileorectostomies. 11/3 and 13/8 patients could return
      to his or her original occupation. The importance of operations planed and
      carried out according to the patients personal interest is emphasized. Some
      special complications and the results of their treatment are discussed.

PMID- 8152786
TI  - [Granular cell (Abrikosov) tumors treated with CO2 laser].
AB  - In five cases Abrikosoff-tumors were recognized and examined by electron
      microscope and immunohistochemical methods. The site of origin was at three
      patients the larynx and at 2 patients the tongue. The authors are dealing with
      the CO2-laser as a new treatment possibility of granular cell tumors. Since years
      they have not seen recurrences. Because of the painless postoperative period, the
      quick recovery and good functional results CO2-laser surgery seems to be the
      treatment of choice in these cases.

PMID- 8152787
TI  - [An unusual case of congenital trigger finger].
AB  - A rare case of the congenital digitus saltans is discussed. The differences
      between the more frequent adult form and the congenital form are reviewed
      according to the clinical signs. The literature is reviewed. The possible
      etiological factors are discussed.

PMID- 8152788
TI  - [The lecture].
AB  - The author reviews the rules of conduct to be followed in lectures and he
      identifies a number of advices, useful for young colleagues. The fundamental
      ethical goal of lectures is to serve the audience as well as possible. The author
      touches upon the most important general rules of oral communications such as
      punctuality, discipline of remaining within time limitations, but he also
      describes advices how to work and deliver talks lectures. In conclusion he
      elaborates on his own view regarding the lecture opportunities that grow in our
      days, the effectiveness of which, however, leaves much to be desired.

PMID- 8152789
TI  - [Remembering Pal Ferencz].

PMID- 8152790
TI  - [Medical ethics, past and present].

PMID- 8152791
TI  - Retroviral capture of c-erbB proto-oncogene sequences: rapid evolution of
      distinct viral genomes carrying mutant v-erbB genes with different transforming
      capacities.
AB  - The evolution of oncogene-transducing retroviruses was followed by studying the
      genomes of five new, erbB carrying retroviruses. These viruses, isolated from
      cells of one chicken infected with Rous Associated virus 1 (RAV-1), had captured
      c-erbB sequences as a consequence of RAV-1 integration into the host genome.
      Their genome structures were distinct; however, their v-erbB genes had sustained
      identical 5' and 3' deletions and the v-erbB-env junctions were identical at the
      nucleotide level. The results therefore strongly suggest that all five viruses
      originate from the same capture event. Sequence analyses of the v-erbB genes from
      three of these viruses revealed that one of them had undergone no further
      mutation and lacked detectable capacity to transform cells, therefore probably
      representing an 'early' form of transducing virus. The two other v-erbB genes
      contained distinct mutations and differed in their potential to induce fibroblast
      and erythroblast transformation; they therefore probably represent later
      derivatives of the virus that captured the erbB oncogene. The data suggest that
      the initial retrovirus rapidly underwent many alterations after capture of c-erbB
      sequences, already in the RAV-1 infected bird as well as during subsequent in
      vitro isolation procedures. The changes involve both major rearrangements of the
      genome as well as point mutations that activated the erbB oncogene.

PMID- 8152792
TI  - Partial inactivation of the RB product in a family with incomplete penetrance of
      familial retinoblastoma and benign retinal tumors.
AB  - While familial retinoblastoma has served as the paradigm for the two-hit theory
      of tumorigenesis and for the concept of the tumor suppressor gene, the etiology
      of incomplete penetrance of familial retinoblastoma is poorly understood. To
      address the molecular basis for this phenotype we have studied the functional
      properties of a mutant Rb gene identified in a kindred with incomplete penetrance
      of familial retinoblastoma and evidence for regressed retinal lesions
      (retinomas). In contrast to all previously isolated RB mutant proteins, we
      demonstrated that the mutant product from this kindred retained the wildtype
      properties of nuclear localization, the ability to undergo hyperphosphorylation
      in vivo, and the capacity to suppress growth of RB(-) cells. Protein binding
      ('pocket') activity, however, was defective defining a new class of RB mutant
      with partial inactivation. The presence of this unique RB mutant in the germline
      of obligate carriers with incomplete penetrance and regressed retinal lesions
      suggests a molecular basis for this phenotype and supports the hypothesis that a
      minimum 'RB threshold' level of protein binding activity is required to suppress
      tumorigenesis.

PMID- 8152793
TI  - Thymic lymphomas in interleukin 9 transgenic mice.
AB  - Transgenic mice overexpressing the interleukin 9 gene were generated to study the
      biological activity of this cytokine in vivo. Although no major histological or
      morphological modifications of the lymphoid system were observed in most animals,
      approximately 7% of transgenic mice developed thymic lymphomas at the age of 3-9
      months. The tumor cells, which were clonal, with unique T cell rearrangements,
      were double positive for the expression of CD4 and CD8. The need for additional
      transforming events, suggested by the low incidence of spontaneous tumors, was
      further indicated by the high susceptibility of the transgenic animals to
      injections of low doses of N-methyl-N-nitrosourea, a chemical carcinogen with a
      thymic tropism. Expression of interleukin 9 was required for optimal tumor growth
      in vivo, as one of the tumors studied, which had lost the transgene, was much
      more efficiently transplanted into transgenic than in normal mice. Moreover, the
      in vitro proliferative activity of interleukin 9 on cell lines derived from such
      transgene-negative tumors suggests that an autocrine loop mediates the
      proliferation of these cells in vivo. Taken together, these results indicate that
      dysregulated IL-9 expression could be involved in the development of some T cell
      malignancies.

PMID- 8152794
TI  - Wild-type human p53 activates the human epidermal growth factor receptor
      promoter.
AB  - We show that wild-type human p53 transactivates the human epidermal growth factor
      receptor (EGFR) promoter in vivo in a dose-dependent manner, implicating p53 in
      promotion of cell proliferation. This activation is sensitive to the expression
      of cellular oncoprotein MDM2 and human papillomavirus type 18 (HPV-18) E6
      protein. The p53 response element is localized within -15 and -569 of the
      promoter. The EGFR promoter does not have a TATA box, and has low activity in
      Saos-2 cells in the absence of p53. Results from our in vivo transient
      transfection assays suggest that p53-binding sites, without any other known
      promoter element, can act as bidirectional promoters in the presence of wild-type
      p53. Gel retardation analyses suggest that p53 may serve to nucleate TBP on a
      promoter. We propose that p53 successfully nucleates the transcription complex,
      possibly via direct interaction with TFIID, and activates the EGFR promoter.

PMID- 8152795
TI  - Overlapping domains on the p53 protein regulate its transcriptional activation
      and repression functions.
AB  - Wild-type p53 has been shown to inhibit transcription from several viral and
      cellular promoters without known p53-binding sites, while transactivating
      promoters with p53-binding sites. Using a series of N- and C-terminal p53
      deletion mutants and wild-type p53, we have defined the domains on p53
      responsible for its transcriptional functions. To test transcriptional activation
      by p53 we have used a promoter-chloramphenicol acetyltransferase (CAT) construct
      containing synthetic p53-binding sites. To check transcriptional inhibition by
      p53 we have used a human cytomegalovirus immediate-early promoter construct, CMV
      CAT. Using transient transfection-transcription assays in Saos-2 cells, we
      determined that the p53 transcriptional activation and repression domains overlap
      at the N-terminus. This suggests the possibility that the same transcriptional
      machinery is involved in both functions. A C-terminal deletion up to amino acid
      327 (del 393-327) eliminated repression of CMV-CAT, while preserving the
      transactivation function to a large extent. Using gluteraldehyde cross-linking
      experiments, we observed that the mutant del 393-327, which is transactivation
      competent, but repression-defective, could not oligomerize. Thus, oligomerization
      of p53 is not required for transactivation, but may be essential for repression.
      Interestingly, transactivation by the oligomerization-defective mutant could be
      inhibited by cotransfection with a plasmid expressing the transforming mutant p53
      175H.

PMID- 8152796
TI  - Loss of heterozygosity and homozygous deletions on 9p21-22 in melanoma.
AB  - Recent studies have implicated chromosome 9p21-22 as a location for a gene
      involved in cutaneous melanoma (CM). Deletion mapping in 35 matched tumour
      constitutional DNA pairs from metastatic melanomas (including one melanoma cell
      line) and one dysplastic naevus has been performed using six short tandem repeat
      polymorphic (STRP) markers (D9S157-D9S162-IFNA-D9S171-DS9126-D9S10 4 ) which span
      approximately 19 cM across the 9p21-22 region. Both heterozygous and homozygous
      deletions were observed across the region in melanomas from both sporadic and
      familial cases. Overall 57% (20/35) of the samples displayed some form of loss. A
      deletion map identifies two areas of common loss either side of the interferon
      gene cluster. Familial CM has previously been shown to link to the more proximal
      of these regions. The deleted region distal to IFNA has not been previously
      described in melanoma. The results imply the involvement of more than one tumour
      suppressor gene on 9p in CM.

PMID- 8152797
TI  - Suppression of v-sis-dependent transformation by the transcription factor, Egr-1.
AB  - The transcription factor Egr-1, stimulates the activity of a number of genes and
      inhibits other genes, by binding to the sequence GCGGGGGCG in 5' enhancer
      regions. However, the functions of Egr-1 are obscure in spite of its rather
      ubiquitous expression. Egr-1 may play a role in proliferation in mitogen
      stimulated cells but its expression is also correlated with the differentiated
      state in teratocarcinoma cells. The constitutive expression of Egr-1 appears to
      have little effect on the growth rate of normal immortalized cell-lines. We show
      that in NIH3T3 cells that are conditionally transformed by the expression of v
      six, the presence of Egr-1 is inhibitory to the production of transformed
      colonies (foci) and to growth in soft agar. In addition, the first appearance of
      tumors in nu/nu mice is delayed in tumorigenicity tests with cells that over
      express Egr-1 and tumor growth is suppressed compared to control cells. We used a
      series of fragments of Egr-1 cloned into expression vectors to show that not only
      full length, but also truncated Egr-1 fragments inhibit colony formation. Using
      deletion mutants, we observed that this inhibitory activity is dependent on the
      presence of the DNA-binding 'zinc-finger' region. Wilm's tumor protein, WT1,
      (known to be a tumor suppressor gene) that exhibits the same DNA binding activity
      is also inhibitory. In contrast, colony formation is stimulated by an Egr-1
      antisense RNA-expressing plasmid, since colonies grow rapidly and the colony
      forming frequency is higher than in the presence of v-sis alone. We conclude that
      proteins containing the Egr-1 'zinc-finger' domain can bind to the regulatory
      regions of one or more genes that are required for the transformation of
      fibroblasts by v-sis thus inhibiting transformation. One function for Egr-1
      implied by these results is the restraint of transformed growth in mitogen
      stimulated cells.

PMID- 8152798
TI  - Sequence specificity in the recognition of the epidermal growth factor receptor
      by the abl Src homology 2 domain.
AB  - The transforming activity of the abl gene product requires a functional src
      homology 2 (SH2) domain. An assay was developed to evaluate this function by
      examining binding of a bacterially-expressed abl SH2 domain to the activated EGF
      receptor, used as a surrogate tyrosine phosphorylated protein. The sequence
      specificity of this interaction has been explored with a series of point mutants
      of EGF receptor. Analysis of equilibrium binding reveals that substitution of
      Tyr1086 for Phe in the EGF receptor produced a 10-fold reduced affinity for abl
      SH2 domain binding as compared to the wildtype receptor. Moreover, a
      phosphorylated peptide modeled on the sequences surrounding Tyr1086 specifically
      inhibits abl SH2 binding, with an IC50 of approximately 10 microM. Evaluation of
      a series of additional peptides, modeled on the Tyr1086 sequence, revealed that
      the carboxy terminal residues directly next to the phosphotyrosine were
      particularly critical to this binding. Molecular modeling studies of the pTyr1086
      peptide revealed the potential hydrophobic, ionic and hydrogen bonding
      interactions involved in the functions of the abl SH2 domain.

PMID- 8152799
TI  - Activation of type D phospholipase by serum stimulation and ras-induced
      transformation in NIH3T3 cells.
AB  - Mitogenic stimulation of NIH3T3 fibroblasts with growth factors or ras oncogenes
      is associated with an increase in the levels of phosphorylcholine and
      diacylglycerol. Both metabolites could be generated as a result of direct
      activation of a phosphatidylcholine-specific phospholipase C (PC-PLC) or by a
      more complex pathway, involving activation of phospholipase D followed by choline
      kinase and phosphatidic acid-hydrolase. We show evidence indicating that the
      generation of phosphorylcholine and diacylglycerol follow independent mechanisms
      in both serum-treated and in ras-transformed NIH3T3 cells. No significant
      activation of a PC-PLC enzyme was observed. Instead, activation of a
      phosphatidylcholine-specific phospholipase D (PC-PLD) was detected. Moreover,
      while a fivefold constitutive activation of the endogenous PLD activity and a
      twofold increase on the levels of phosphatidic acid were observed in ras
      transformed cells, very small alterations on these parameters were detected at
      late times after serum stimulation of quiescent cells. Thus, cell proliferation
      induced by ras oncogenes in fibroblasts cells may be functionally linked to
      activation of a PC-PLD enzyme. The differences found in the activation of this
      enzyme between ras-transformed and normal cells may constitute an important
      difference in mitogenic signalling between normal and transformed cells.

PMID- 8152800
TI  - Molecular cloning and characterization of human ERM, a new member of the Ets
      family closely related to mouse PEA3 and ER81 transcription factors.
AB  - The ets-related transcription factors PEA3 and ER81 have recently been isolated
      and characterized in the mouse. They share 95% identity in a 85 amino acid (AA)
      domain termed the ETS domain which is responsible for DNA binding, and therefore
      they form an Ets family group. By screening a human testis cDNA library with a
      probe containing the mouse PEA3 ETS domain, we isolated a 2.2 kb clone containing
      a 510 AA open reading frame. Since the ETS domain, which is localized in the
      carboxy terminal region of the encoded protein, is 95% and 96% identical to that
      of PEA3 and ER81, respectively, we named this new member 'Ets Related Molecule
      PEA3-like' (ERM). Although the first 120 AA in the amino-terminal region of ERM
      share 47% identity with PEA3 and 66% with ER81, ERM contains a central region of
      approximately 35 AA not found in the two mouse proteins. Gel shift analysis
      indicates that the full-length ERM protein is able to bind specifically to an
      oligonucleotide containing the consensus nucleotide core sequence GGAA recognized
      by the Ets proteins. Moreover, in vitro translation of 83 AA of the ERM ETS
      domain led to the production of a truncated protein which also binds to DNA.
      Though differential expression is observed in primary tumors and normal
      lymphocytes do not express ERM, this gene is almost ubiquitously expressed in
      human normal tissues. ERM mRNA is highly expressed in brain as well as in
      placenta and, to a lesser degree, in lung, pancreas, and heart. Moreover, almost
      all human cell lines tested express it at varying levels. In mouse tissues, we
      showed that PEA3 and ER81 mRNAs display restricted expression, whereas ERM is
      almost ubiquitously expressed as observed for human tissues. Altogether these
      results indicate that ERM is clearly a new ets family member and not the human
      equivalent of PEA3 or ER81.

PMID- 8152801
TI  - Induction of the c-ski proto-oncogene by phorbol ester correlates with induction
      of megakaryocyte differentiation.
AB  - Overexpression of v-ski blocks the terminal differentiation of chicken
      erythroblasts, and in cooperation with v-sea causes transformation of these
      cells, indicating that c-ski may play a role in regulating either proliferation
      or differentiation in hematopoietic cells. We examined c-ski expression in four
      different myeloid cell lines which can be induced to differentiate by exposure to
      phorbol 12-myristate 13-acetate (PMA). Two of the cell lines are multipotent and
      have the ability to differentiate into either erythrocytes or megakaryocytes
      (K562 and HEL cells), one cell line differentiates exclusively into
      megakaryocytes (CHRF-288-11), and the fourth cell line differentiates into either
      monocytes or granulocytes (HL-60). Our findings indicate that c-ski mRNA is up
      regulated by PMA only in those cell lines which respond by differentiating along
      the megakaryocyte lineage. The extent of differentiation and the observed
      increase in c-ski mRNA levels are positively correlated with the PMA
      concentration used to induce differentiation. Experiments in which CHRF-288-11
      cells were treated with the protein kinase C (PKC) activator bryostatin 1
      indicate that c-ski mRNA induction is not a general effect of PKC activation. The
      results strongly suggest that c-ski expression is correlated with megakaryocyte
      maturation.

PMID- 8152802
TI  - Kras-2 alleles, mutations, and lung tumor susceptibility in the mouse--an
      evaluation.
AB  - Lung Tumor Susceptibility (LTS) in the mouse has been shown to be influenced by
      loci within the Major Histocompatibility Complex (MHC) and the Kras-2 regions. In
      crosses between susceptible and resistant strains, one allele of Kras-2 has been
      linked with a high LTS, whereas the other allele has been linked with a low LTS.
      Furthermore, these Kras-2 alleles affect differently the occurrence of Kras-2
      mutations in lung tumors. In this study we evaluated the relationship between
      LTS, Kras-2 alleles and Kras-2 mutations, using Recombinant Congenic Strains with
      identical MHC haplotypes. The Kras-2 region indeed influences the frequency of
      Kras-2 mutations in N-ethyl-N-nitrosourea-induced lung tumors. These mutations
      are associated with larger tumors. However, Kras-2 affects LTS only marginally.
      Several strains with identical Kras-2 alleles and mutation frequency differ
      widely in LTS, while some strains with different alleles and mutation frequency
      do not. We conclude that a considerable part of the genetic variability in LTS is
      caused by LTS-loci other than Kras-2 and MHC.

PMID- 8152803
TI  - The oncogenic transcription factor IRF-2 possesses a transcriptional repression
      and a latent activation domain.
AB  - IRF-1 and IRF-2 are two structurally related transcription factors originally
      identified as regulators of the type I interferon (IFN) system. IRF-1 functions
      as an activator whereas IRF-2 binds to the same cis-elements and can repress IRF
      1 action. More recently these two factors have been shown to act in a mutually
      antagonistic manner to regulate cell growth; overexpression of the repressor IRF
      2 leads to cell transformation, whereas concomitant overexpression of IRF-1 leads
      to reversion. Previous studies have identified DNA-binding domains in IRF-1 and
      IRF-2 and an activation domain in IRF-1. In the present study we show that IRF-2
      also possesses a transcriptional repression domain in its carboxyl terminal
      region. We further observe that a LexA-IRF2 fusion can inhibit the function of an
      activator positioned nearby in the promoter. Thus, repression by IRF-2 may
      involve both competition with IRF-1 for binding to the promoter as well as the
      'silencing' of nearby activators. Furthermore, we demonstrate the presence of a
      latent activation domain in the central region of IRF-2 and speculate that IRF-2
      may contribute to gene activation under certain conditions.

PMID- 8152804
TI  - Excess early signaling activity inhibits cellular chemotaxis toward PDGF-BB.
AB  - Chemotaxis, directed migration toward a gradient of a soluble substance, requires
      a cell to spatially distinguish the concentration of a chemoattractant at one end
      relative to its opposite end. Platelet-derived growth factor (PDGF) is a potent
      mitogen and chemoattractant. In the current study, we attempted to interfere with
      PDGF-BB mediated chemotaxis by abnormal expression of potential early components
      of the signaling cascade. We find that expression of the PDGF homolog v-Sis
      prevents cellular migration toward PDGF-BB, indicating that autocrine production
      of a PDGF receptor ligand will prevent the chemotactic response to exogenously
      added ligand. In addition, while it is known that PDGF receptor mutants incapable
      of activating tyrosine kinase activity cannot transduce a signal for mitogenesis
      or chemotaxis, the effects of excess tyrosine kinase activity on PDGF mediated
      chemotaxis have not been tested. We demonstrate that cells expressing
      constitutively active tyrosine kinase genes such as v-fms, v-fes, or v-src fail
      to migrate toward PDGF-BB whereas expression of the serine/threonine kinase v-mos
      does not block the chemotactic response. The results demonstrate that chemotaxis
      may be prevented by excess production of either ligand, receptor activity, or
      downstream signaling molecule. In addition, our results show that the signals
      that mediate chemotaxis are separable from those that regulate unstimulated
      random motility in the same cells.

PMID- 8152805
TI  - Products of the TAL2 oncogene in leukemic T cells: bHLH phosphoproteins with DNA
      binding activity.
AB  - The TAL2 gene is activated as a result of the (7;9) (q34;q32) translocation, a
      chromosome defect found in the malignant cells of some patients with T-cell acute
      lymphoblastic leukemia (T-ALL). TAL2 potentially encodes a basic helix-loop-helix
      motif that is highly related to those specified by TAL1 and LYL1, distinct genes
      that have also been implicated in T-ALL. In this report we show that leukemic
      cells bearing the (7;9) (q34;q32) translocation express a TAL2 gene product of
      108 amino acids. In leukemic cells this product exists in both a phosphorylated
      (pp13TAL2) and an unphosphorylated (p12TAL2) form. Serine residue 100 is the
      major site of TAL2 phosphorylation in vivo, and it serves as an effective in
      vitro substrate for mitogen-activated protein (MAP) kinases such as ERK1. TAL2
      polypeptides interact in vivo with the E2A gene products (E47 and E12) to form
      bHLH heterodimers that bind DNA in a sequence-specific manner. The TAL2
      polypeptides do not bind DNA by themselves, however, suggesting that their
      functional properties may be contingent upon association with other bHLH
      proteins. Taken together, the properties of TAL2 evaluated here broadly resemble
      those described previously for TAL1, and therefore support the idea that both
      proteins promote T-ALL by a common mechanism.

PMID- 8152806
TI  - The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves
      two distinct loci on the X chromosome.
AB  - A high proportion of synovial sarcomas contain the reciprocal translocation
      t(X;18)(p11.2;q11.2). We have previously localized the breakpoint on the X
      chromosome between the X chromosome marker DXS255 and an ornithine
      aminotransferase (OAT) pseudogene region designated OATL2. Subsequently by
      fluorescence in situ hybridization (FISH) we provided evidence that YACs
      corresponding to the OATL2 locus spanned the break-point. In order to confirm the
      position of this breakpoint cosmids corresponding to the OATL2 region were
      isolated. Most of these cosmids mapped to four cosmid contigs designated C1-C4.
      Analysis of two contigs, C1- and C4, using FISH established that in four of six
      synovial sarcomas examined the breakpoint occurs between these two contigs: C1
      lies distal to the break-point while C4 is proximal. In contrast we provide
      evidence that the breakpoint in the remaining two tumours mapped to a second
      pseudogene region called OATL1 that is telomeric to the OATL2 locus. This
      heterogeneity of the breakpoint position on the X chromosome explains why in
      previous mapping studies there have been discrepancies between the results
      obtained by different laboratories.

PMID- 8152807
TI  - Analysis of p53 in human cutaneous melanoma cell lines.
AB  - Mutations in the p53 tumour suppressor gene have been detected in a variety of
      human malignancies. Mutations have been found predominantly in conserved regions
      two to five. Our aim was to analyse p53 at the protein and DNA level in seven
      melanoma cell lines of cutaneous origin (HMB-2, DX3, LT5.1, MJM, SK23, A375P and
      A375M), including two parental/metastatic derivatives (A375P and A375M; DX3 and
      LT5.1). By immunohistochemical staining with three mouse monoclonal antibodies
      and a rabbit polyclonal serum, it was possible to observe differential nuclear
      expression of p53. The quantitation of p53 protein levels by ELISA correlated
      with the nuclear staining pattern. Western blotting showed an intact p53 protein
      in all cell lines; p53 was polymorphic in three cell lines (MJM, A375P and
      A375M). DNA sequencing studies showed that all cell lines had wild type p53.
      These results suggest that p53 is unlikely to play a significant role in the
      genesis of cutaneous melanoma.

PMID- 8152808
TI  - Expression of two novel eph-related receptor protein tyrosine kinases in mammary
      gland development and carcinogenesis.
AB  - To investigate the involvement of protein tyrosine kinases (PTKs) in the growth
      control of mammary epithelial cells, we have used PCR based cloning to identify
      PTKs expressed in a mouse mammary epithelial cell line. This approach led to the
      isolation of two receptor PTKs of the eph-related subfamily; myk-1, a novel
      member expressed predominantly in lung, heart and mammary gland and myk-2, a
      close relative of the human eck gene. Northern blot analysis of RNA from mouse
      mammary glands at different stages of development revealed that myk-1 and myk-2
      expression is induced at puberty and differentially regulated during the estrus
      cycle. myk-1 and myk-2 expression was down-regulated during the pregnancy induced
      differentiation of the mammary gland. Over-expression of myk-1 and myk-2 was
      found in the undifferentiated and invasive mammary tumors of transgenic mice
      expressing the Ha-ras oncogene. In contrast, no elevated expression of either
      gene could be detected in the well differentiated and non-metastatic mammary
      tumors of c-myc expressing transgenic mice. These results indicate that myk-1 and
      myk-2 expression is induced during the proliferation of the mammary gland and
      down-regulated by its differentiation.

PMID- 8152809
TI  - The mdm-2 oncogene is translocated and overexpressed in a murine plasmacytoma
      cell line expressing wild-type p53.
AB  - The cellular p53 protein has been demonstrated to possess growth-inhibitory
      activity. Recent work suggests that the murine double minute gene (mdm-2) encodes
      a protein that may function as a cellular regulator or mediator of p53 function.
      We were interested in determining if the mdm-2 gene was overexpressed in mouse
      tumor cells, in particular mouse plasmacytomas that harbor wild type-p53 protein.
      A novel chromosomal translocation of the mdm-2 gene was detected in the SP2 cell
      line, that is derived from plasmacytoma MOPC21. The translocation results in a
      head-to-head arrangement of the mdm-2 gene (chromosome 10) with the
      immunoglobulin C kappa gene (chromosome 6), analogous to the translocations that
      activate the c-myc gene in murine plasmacytomas. Based on Northern blot analysis,
      the translocation induces a 10-fold elevation of mdm-2 RNA. Primer extension
      assays demonstrate that the 5' end of the mdm-2 RNA from the translocated gene is
      colinear with the 5' mdm-2 mRNA from an unrearranged gene, suggesting that the
      mRNA and encoded protein are unaltered. This chromosomal translocation represents
      the first example in which mdm-2 overexpression is activated by a genetic
      alteration other than gene amplification.

PMID- 8152810
TI  - Molecular cloning of a recombinant retrovirus carrying a mutated envAKR-mycMH2
      fusion gene immortalizing cells of the monocytic-macrophage lineage.
AB  - The VN-11 recombinant retroviruses, originally generated by co-transfection of
      the avian MH2 and AKRv viral genomes, were molecularly cloned from an infected
      mouse cell line named N11. The analysis of the proviral genome sequence from one
      of these recombinants showed a possible envAKR-mycMH2 fusion. Point mutations
      were also found in this envAKR-mycMH2 gene. The cloned viral genome was co
      transfected with the neo gene into the psi 2 packaging cell line. Selected clones
      were shown to transcribe the viral genome and supernatants from these cultures,
      containing C-type particles, were used to infect primary cultures from mouse
      lymphoid tissues and brain. Proliferating macrophages and microglial cell clones
      were obtained, indicating that various types of cells of the mouse monocytic
      macrophage lineage can be immortalized in spite of the absence of selection or
      special growth conditions.

PMID- 8152811
TI  - Transfection and expression of mutant p53 protein does not alter the in vivo or
      in vitro growth characteristics of the AA/C1 human adenoma derived cell line,
      including sensitivity to transforming growth factor-beta 1.
AB  - Mutation of the p53 gene is thought to be a late event in human colorectal
      carcinogenesis, involved in the malignant conversion of the adenoma to the
      carcinoma. One of the questions that we hoped to address was whether, in vivo, a
      single mutational event in one p53 gene is sufficient to confer a significant
      growth advantage on a colonic epithelial cell. Such a growth advantage could
      result either from an increase in growth rate and/or loss of response to
      inhibitory growth signals naturally present in the colonic crypt. We therefore
      introduced the pC53-SCX3 143 (Val-Ala) p53 mutation into a non tumorigenic
      adenoma derived cell line, AA/C1, which contained a truncating APC mutation,
      activating K-ras mutation but was wild-type for the p53 protein. High levels of
      mutant p53 protein were detected in the pC53-SCX3 transfected AA/C1 cell lines
      but was found not to affect either the in vitro (colony forming efficiency,
      anchorage independence) or in vivo (tumorigenicity in nude mice) growth, when
      compared to vector control or the parental AA/C1 cell line. In addition, to test
      whether the cells become less sensitive to inhibitory growth factors, the
      response of the cell lines to the naturally occurring growth inhibitor TGF beta
      was also investigated. Even though TGF beta had previously been implicated in the
      control of growth of intestinal epithelium, expression of the mutant p53 protein
      did not affect the sensitivity of the parental AA/C1 cell line to TGF beta. Under
      the experimental conditions tested expression of the 143 (Val-Ala) p53 protein
      was unable to affect the in vitro or in vivo growth characteristics of the
      adenoma derived AA/C1 cell line. When compared to other studies, these results
      suggest that the genetic background of the individual recipient cell may greatly
      influence the effect of expression of a particular p53 mutation.

PMID- 8152812
TI  - Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis
      factor.
AB  - NF-kappa B is an inducible transcription factor that regulates the expression of
      numerous genes involved in immune and inflammation responses and in cellular
      growth control. Typically, NF-kappa B is localized in the cytoplasm complexed
      with members of the I kappa B family. The most well characterized form of NF
      kappa B is comprised of a heterodimer of a 50 kD (p50/NFKB1) and a 65 kD
      (p65/RelA) protein. This heterodimeric protein was thought to be primarily
      responsible for transcriptional regulation of target genes. However, recent
      studies have led to the identification of other kappa B binding proteins such as
      c-Rel, RelB and p52 (NFKB2/lyt-10) although their role in gene regulation has
      been less clear. Here, using gel mobility shift assays as well as a highly
      sensitive DNA-protein crosslinking assay, we provide evidence for the existence
      of multiple tumor necrosis factor (TNF)- inducible kappa B binding complexes
      containing various members of the NF-kappa B/Rel family, namely p50 and p65 as
      well as the c-Rel and p52 oncoproteins. Dimeric complexes containing various
      combinations of these proteins appear rapidly in nuclei of TNF-alpha-stimulated
      cells and include, along with a p50-p65 heterodimer, p50-c-Rel, p65-c-Rel, p52-c
      Rel and p52-p65 complexes. The presence of multiple inducible complexes
      containing distinct combinations of NF-kappa B/Rel family members indicate that
      specific kappa B responsive genes may be regulated in an NF-kappa B subunit
      dependent manner.

PMID- 8152813
TI  - Interaction of the E6 protein of human papillomavirus with cellular proteins.
AB  - The E6 proteins of the oncogenic Human Papillomavirus (HPV) types 16 and 18 are
      known to bind two cellular proteins, the tumor suppressor protein p53 and a 100
      kDa protein named E6-AP. In this paper we describe the expression and
      purification of biologically active E6 fusion proteins and their specific
      association with additional cellular proteins. HPV16E6 specifically associated
      with at least seven cellular proteins which have been designated pp212, pp182,
      p100, p81, p75, p53 and p33 respectively, on the basis of molecular mass and
      phosphorylation. We have also shown that the complex of cellular proteins
      associated with HPV16, 18, 6 and 11 E6 proteins contains a protein kinase. This
      protein kinase phosphorylated exogenous histone H1 and the E6 associated protein
      pp182.

PMID- 8152814
TI  - Guanine-rich (GGNNGG) elements at chromosomal breakpoints interact with a loop
      forming, single-stranded DNA-binding protein.
AB  - Proto-oncogene-activation is frequently preceded by chromosomal translocations.
      Several models suggest that DNA single-strands and loops may serve as
      intermediates in the process of illegitimate recombination. Guanine-rich,
      repetitive elements are preferred sites of chromosomal exchange and can undergo
      conformational changes which result in the generation of single-stranded DNA.
      Here we describe a single-stranded DNA-binding protein which binds specifically
      to guanine-rich elements at the breakpoints of human reciprocal translocations,
      including the t(14;18), t(2;8), t(9;22), t(15;17) and t(4;11) in leukemia and
      lymphoma. The primitive binding consensus consists of two guanine-residues on
      either side separated by a spacer of at least two nucleotides (GGN-NGG). Binding
      activity is unaltered by a spacer length of up to 46 nucleotides. These data
      suggest that the protein has the unique ability to form or stabilize DNA-loops
      and may thus play a general role in recombination.

PMID- 8152815
TI  - Tri-meridional analysis using arbitrary meridians: a new solution.
AB  - A new solution is presented for the evaluation of the spherocylindrical
      components of curvature or refraction from measurements taken along three
      distinct, arbitrary, meridians. Unlike previous approaches, the axis direction is
      found first, thereby making sphere and cylinder evaluation relatively simple. The
      derivation of the solution is reasonably uncomplicated using straightforward
      trigonometrical operations.

PMID- 8152816
TI  - Comparison of the techniques of videorefraction and static retinoscopy in the
      measurement of refractive error in infants.
AB  - Photorefraction has been suggested as a suitable method of screening for
      refractive error in infants. The relative performance of cycloplegic and non
      cycloplegic videorefraction and cycloplegic retinoscopy was investigated on 150
      infants. Under cycloplegic conditions the correlation between findings for
      spherical error (Rxy = 0.70) was compatible with a previous study. However, where
      cycloplegia was not used for videorefraction, there was poor agreement between
      the two techniques in the case of astigmatic error, and all types of ametropia.
      Interobserver repeatability was very high both for cycloplegic retinoscopy (Rxy =
      0.96 spherical error, and Rxy = 0.75 astigmatic error) and for videorefraction
      measurements (Rxy = 0.95 horizontal meridian of photograph and Rxy = 0.85
      vertical meridian). Intraobserver repeatability was also good, both for
      cycloplegic retinoscopy (Rxy = 0.91 spherical error and 0.82 astigmatic error)
      and for videorefraction with regard to spherical errors (Rxy = 0.84). Throughout
      the experiments videorefraction measurements of astigmatic errors proved less
      consistent when compared with cycloplegic retinoscopy, and to its internal
      reliability.

PMID- 8152817
TI  - Facial characteristics in children with Down's syndrome and spectacle fitting.
AB  - Significant refractive error is very common among children with Down's syndrome
      so the requirement for spectacles for this group is high. The aim of this study
      was to measure the facial characteristics of children with Down's syndrome and to
      compare them with two previous studies which have aided the design of children's
      spectacle frames. The study was carried out in two schools in South Wales,
      measuring 20 children between the ages of 3.6 and 14.4 years. The results show
      that between the ages of 7 and 14 years, facial characteristics of children with
      Down's syndrome do not change with age and rarely coincide with those of other
      children, either of a similar age or younger. Thus children with Down's syndrome
      cannot be fitted satisfactorily with conventional children's frames, and it would
      be desirable for a specially designed range of frames to be made available.

PMID- 8152818
TI  - Risk of accidents among elderly car drivers with visual acuity equal to 6/12 or
      6/15 and lack of binocular vision.
AB  - To document the risk of road accidents associated with minimal visual acuity
      (equal to 6/12 or 6/15) and lack of binocularity (stereoacuity > or = 200 sec
      arc), 1400 drivers who had had an accident during their 70th year were compared
      with 2636 controls randomly selected from the 30,000 70-year-old drivers who had
      had no accident during the same time. Information on visual characteristics and
      demerit points was obtained for all subjects from the Quebec Automobile Insurance
      Board. Mileage and prevailing driving conditions were documented through a mail
      questionnaire. The relative risks of accidents were estimated while controlling
      for traffic convictions, mileage, time spent and frequency of driving during rush
      hours. Drivers with minimal visual acuity alone had the same risk of road
      accidents as other drivers (OR = 0.97 CI 95%: 0.68-1.38). The risk of accidents
      among drivers with both minimal visual acuity and lack of binocularity was
      moderately higher than among other drivers (OR = 1.23, CI 95%: 0.88-1.72).

PMID- 8152819
TI  - Changes in ocular and visual variables during the menstrual cycle.
AB  - For most women the menstrual cycle is an integral part of a major portion of
      their lives. There is widespread agreement about the hormonal changes that occur
      during the menstrual cycle, but studies of physical and psychological changes
      have been more controversial. The influence of the menstrual cycle on various
      ocular and visual variables has been investigated. These include the potential
      protective role of female sex hormones in some ocular conditions, reports of
      reduced tolerance to contact lens wear, and changes in visual performance during
      the cycle. This paper critically reviews the literature on visual and ocular
      changes across the normal human menstrual cycle. Stereotypical views of an
      impairment of performance premenstrually and during menstruation are challenged.
      The shortcomings of, and difficulties associated with, much of the research on
      this topic are highlighted.

PMID- 8152820
TI  - Review of past and present techniques of measuring corneal topography.
AB  - Various methods of measuring corneal topography are described. The advantages and
      disadvantages of the principles used in the measurement of corneal shape by the
      various techniques are discussed. The corneal surface may be described in a
      number of ways; some researchers have used conic sections while others have used
      more complex polynomial expressions. Computer algorithms have also been developed
      to calculate quantitative measures of corneal topography to augment the
      information obtained from topographical maps. These descriptors are discussed in
      this article.

PMID- 8152821
TI  - Investigation of accommodative and binocular function in dyslexia.
AB  - The visual correlates of dyslexia are the subject of controversy, and much
      evidence suggests that they may include some aspects of binocular and
      accommodative function. These factors were investigated in 43 control and 39
      dyslexic children, who were matched for age, sex and performance intelligence
      quotient. The dyslexic group exhibited significantly lower positive and negative
      vergence reserves, and vergence instability when the eyes were dissociated at
      near. Their amplitudes of accommodation also were significantly reduced. However,
      other measures including dissociated and associated heterophoria and
      accommodative lag and facility were similar in both groups. The stability of
      motor ocular dominance, as assessed with a modified Dunlop test, was similar in
      both groups. The results of a simulated reading visual search task suggested that
      the vergence and accommodative dysfunction were not a major cause of the
      dyslexia. Further analyses, using reading-age matched groups, suggested that
      these ocular motor correlates were not attributable to the better reading
      performance in the control group. The most likely remaining explanation is that
      they are, in most cases, non-causal correlates of the dyslexia.

PMID- 8152822
TI  - Three month study of changes in the cornea after computer-determined and
      conventionally-determined contact lens fitting.
AB  - The conventional rigid-lens fitting method uses fluorescein to assess the tear
      layer beneath a trial lens on the corneal surface. A more advanced technique,
      which uses a computer program to determine the back surface specifications of a
      contact lens from a pre-set tear layer thickness, has been studied. No
      significant difference was found in terms of corneal physiological changes
      between the conventionally determined contact lenses and computer-determined
      contact lenses after a three-month wearing period. The results suggest that there
      is little difference in the two methods of fitting. However, the computer
      determined method was found to be more efficient in terms of chair time, and also
      can aid inexperienced rigid lens practitioners to select the appropriate lens
      back surface curves.

PMID- 8152823
TI  - Postlens tear film morphology, lens movement and symptoms in hydrogel lens
      wearers.
AB  - Postlens tear film morphology, lens movement and symptoms were assessed in 100
      subjects wearing hydrogel contact lenses on a daily wear schedule. Postlens tear
      film appearance in specular reflection was categorized as amorphous, coloured,
      striated or dynamic (variable with blinking), and subjects' symptoms were
      assessed using a questionnaire. Non-amorphous appearances were present in 25% of
      subjects and occurred approximately equally with HEMA, Acuvue, Igel 55 and other
      lens types. Patterned appearances were found to be associated with reduced lens
      movement (Kruskal-Wallis ANOVA, P < 0.001). The most common symptom (dryness) was
      not significantly related to postlens tear film appearance. Postlens tear film
      morphology was shown to be a determinant of lens movement, but may be unrelated
      to common symptoms.

PMID- 8152824
TI  - Spatial summation of the differential light threshold as a function of visual
      field location and age.
AB  - Static differential light thresholds were measured as a function of stimulus size
      (Goldmann sizes I-V) along four visual field meridia (75, 165, 255 and 345
      degrees) with the Humphrey Field Analyzer 640. Data were obtained for both young
      (n = 10, age 23.6 +/- 2.9 years) and elderly (n = 10, age 72.0 +/- 5.2 years)
      normal subjects. The resulting peripheral spatial summation curves could be
      equated to the foveal data simply by a change in size scale, which increased
      linearly with eccentricity. E2 values, expressing the eccentricity at which
      stimulus size must double for performance to remain comparable to the fovea, were
      in the order of 3-9 degrees. Whilst the rate of scale change is approximately the
      same for both young and elderly observers, differences in performance can be
      explained by a combination of lower sensitivity and a bias in sensitivity towards
      larger stimulus sizes with increasing age.

PMID- 8152825
TI  - Pursuit eye movements in chronic schizophrenics: relationship between increased
      saccades and negative symptoms.
AB  - Smooth pursuit eye movements of chronic schizophrenics (n = 16) and controls (n =
      10) were recorded while subjects tracked a sinusoidally-moving target. Negative
      symptoms in schizophrenics were rated using the Schedule for the Assessment of
      Negative Symptoms. An increased frequency of smooth pursuit eye movement
      abnormalities was found in the schizophrenic group, including greater variability
      of gain and more frequent and larger saccades. Frequency of saccades was
      positively correlated with the Negative Symptoms scales for attentional
      impairment and alogia. The results confirm findings of eye movement dysfunction
      in schizophrenics and provide new evidence that the motor and cognitive
      dysfunctions of schizophrenia may be related.

PMID- 8152827
TI  - Repeatability of post-task regression of accommodation in emmetropia and late
      onset myopia.
AB  - The characteristics of post-task regression of accommodation to pre-task tonic
      accommodation (TA) levels have been examined in a number of studies to clarify
      the nature of the within-task facility for accommodative adaptation. Of special
      interest is the recent observation that significant attenuation of post-task
      regression occurs in late-onset myopes (LOMs) when compared with emmetropes
      (EMMs). These findings have led to speculation that such attenuation may reflect
      a deficit in inhibitory sympathetic innervation to ciliary smooth muscle in late
      onset myopia and hence a predisposition to sustained accommodative adaptation
      which then acts as a precursor to the induced myopia. A consequence of this study
      was that post-task regression may have some value in predicting those individuals
      who may be susceptible to post-task accommodative hysteresis. A pre-requisite for
      such a predictive value is that for a given individual the variation in inter
      trial regression patterns is not significant. The aim of this study is
      principally to investigate the inter-trial variability of post-task regression
      for individual subjects following a sustained near vision task, and to confirm
      further differences that have been reported between EMMs and LOMs with respect to
      the time course of post-task regressions. A modified Canon R1 infrared optometer
      was used to measure accommodation objectively throughout a near task and for 2
      min post-task. Accommodative level was measured following 3 min fixation of a
      high contrast photopic Maltese cross target placed 3 D above the subject's
      baseline TA. Repeatability of post-task regression in 10 EMMs and 10 LOMs was
      assessed by taking measurements on three separate occasions.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8152826
TI  - Mass and centroid of rigid lenses.
AB  - By subdividing a lens design into simpler units it is possible to evaluate its
      mass and locate its centre of mass (the centroid). The constituent subcomponents
      form plane sections of the sphere, or, in the case of aspheric lenses, sections
      of a conicoid. The theory of lens analysis in terms of the conicoidal (and
      spherical) frustrum is discussed and a BASIC computer program is presented to
      perform the calculations for spherical multicurve contact lenses.

PMID- 8152828
TI  - Analysis of method-comparison data.
AB  - Method-comparison studies, in which new 'candidate' techniques are compared with
      an established 'gold standard', feature commonly in optometric research.
      Investigators often analyse their findings using least squares regression,
      Pearson's product-moment correlation coefficient and the paired t-test. We
      describe more appropriate methods which include: the 'limits of agreement', the
      intraclass correlation coefficient, and Deming's method for estimating a straight
      line fit. Comparisons between methods are made with the aid of a computer
      simulation. Computer program listings are provided to assist in implementing the
      analyses.

PMID- 8152829
TI  - Toxocara canis-induced murine pulmonary inflammation: analysis of cells and
      proteins in lung tissue and bronchoalveolar lavage fluid.
AB  - The pulmonary immuno-inflammatory reaction and its effect on microvascular
      integrity was studied in Toxocara canis infected BALB/c mice. The investigation
      aimed to compare changes in lung histology and composition of bronchoalveolar
      lavage fluid (BALF) caused by T. canis infection with those described to occur in
      allergic asthma. Groups of (non)-infected mice (1000 ova) were investigated until
      90 days post infection (p.i.). Migration of the larvae through the lungs was
      followed by a rapidly progressing multifocal interstitial and alveolar
      inflammation. Eosinophils and lymphocytes formed perivascular and partially
      peribronchial mixed cellular infiltrates. Lymphocytes with plasma cell morphology
      staining intracellularly for either alpha, epsilon or gamma immunoglobulins were
      demonstrated. BALF, collected from mice infected with either 250, 500 or 1000 ova
      was analysed at 14 and 28 days p.i. A dose-related increase in cell numbers and
      in albumin and IgA concentration was observed. IgE increase was independent of
      the infective dose. Peak values were measured at 14 days p.i. Albumin increase in
      lung homogenate was highest at 28 days p.i. 30% of the lymphocytes consisted of T
      cells carrying Thy-1,2 and L3T4 surface antigens. It is concluded that T. canis
      induced pulmonary inflammation affects the permeability of the microvasculature.
      This is expressed by interstitial oedema and plasma exudation in the airway
      lumen. Both phenomena occur also in allergic asthma. It is suggested that
      increased permeability of the microvasculature is mediated by T cells and
      eosinophils.

PMID- 8152830
TI  - Granulomatous hypersensitivity to Schistosoma mansoni EGG antigens in human
      schistosomiasis. IV. A role for prostaglandin-induced inhibition of in vitro
      granuloma formation.
AB  - The prostaglandins (PG) are known to regulate immune cell function(s) and
      participate in the progression of both acute and chronic inflammatory reactions.
      Using an in vitro model of Schistosoma mansoni egg-induced hypersensitivity
      granulomas, we have delineated the role of immune complexes (IC) in the induction
      and release of PG and their inhibitory effects on granuloma development. The
      hypersensitivity-type granuloma reaction to soluble egg antigen (SEA) was
      examined using a model of in vitro granuloma formation. Our results show that
      granuloma formation was dramatically suppressed by the addition to the granuloma
      cultures of IC, PGE1, PGE2, while PGF2 alpha had no significant effect. The
      inhibition of the PG function was achieved by the introduction of anti-PG
      antibodies that blocked suppression of granuloma formation. It appears in this
      model system that IC may inhibit the activity of granuloma formation by
      stimulating the monocyte-macrophage lineage to release inhibitory mediators. Our
      results suggest that the prostaglandins E series may be important in the
      generation and maintenance of suppression of the granulomatous inflammatory
      response to S. mansoni egg antigens.

PMID- 8152831
TI  - Cross-protection between species of the Schistosoma haematobium group induced by
      vaccination with irradiated parasites.
AB  - Mice vaccinated with irradiated cercariae of Schistosoma haematobium, S. bovis
      and S. margrebowiei showed good levels of resistance (38-62%) against an
      homologous challenge, and varying degrees of resistance (19-46%), against
      challenges with closely related species. No protection against S. mansoni was
      induced by vaccination with any of these species. This restricted cross
      protection reflects the close phylogenetic relationship between species of the S.
      haematobium group and indicates that immunologically important epitopes are
      conserved within this species complex.

PMID- 8152832
TI  - Studies on the immunogenicity of a recombinant ookinete surface antigen Pbs21
      from Plasmodium berghei expressed in Escherichia coli.
AB  - Plasmodium berghei ookinete surface antigen (Pbs21), was produced as a fusion
      product with maltose binding protein (MBP) in Escherichia coli and used to induce
      transmission-blocking immunity in mice. Specificity of induced antibody was
      confirmed by Western blotting with native ookinete Pbs21, and by the indirect
      immunofluorescent antibody test on ookinete bloodfilms. Immunized mice were
      infected with P. berghei and transmission to Anopheles stephensi mosquitoes
      determined by both the intensity and prevalence of oocyst infections. Compared
      with a control group immunized with MBP alone the maximum blockade of oocyst
      intensity was 66% in the mice immunized with recombinant MBP-Pbs21. Over nine
      experiments blockade averaged only 33%. By comparison with native Pbs21 protein,
      which usually induces > or = 90% blockade, our data suggests the recombinant
      protein produced in this bacterial system is a less effective immunogen despite
      expressing epitopes recognized by known transmission-blocking monoclonal
      antibodies.

PMID- 8152833
TI  - Toxoplasma gondii: detection of antibodies in human saliva and serum.
AB  - Saliva samples from 27 patients with a recent toxoplasma infection were tested
      for specific IgG, IgM and IgA antibodies to Toxoplasma gondii. Thirteen of the 27
      saliva samples were positive for IgG anti-T. gondii by direct agglutination and 8
      of the 27 were positive for IgM anti-T. gondii by an immunosorbent agglutination
      assay. Twenty of the 27 saliva samples were positive for IgG antibody on
      toxoplasma immunoblots with three major immunodominant antigens; 38, 30 and 35
      kDa. IgA results on toxoplasma immunoblots were positive for all three groups
      tested, recently infected patients, chronically infected and seronegative adults
      without distinguishing between them. The 35 and 43 kDa antigens were the most
      frequently detected proteins. IgM in saliva gave negative or very weak reactions.
      None of the eight seronegative or the 17 chronically infected adults gave
      positive results in any of the tests performed to detect IgG or IgM in saliva.
      Serial saliva and serum samples from a laboratory-infected patient were collected
      and tested for toxoplasma-specific IgG, IgM and IgA. IgG in saliva was detected
      by 27 days post infection (p.i.) and was negative by 81 days p.i.; it detected
      mainly the 38 and 30 kDa antigens. IgM in saliva was detected by 11 days p.i. and
      was negative by 81 days p.i., with no reaction on immunoblots.

PMID- 8152834
TI  - Actinobacillus actinomycetemcomitans recovery from extracrevicular locations of
      the mouth.
AB  - Associations between recovery of Actinobacillus actinomycetemcomitans from
      samples of subgingival plaque, and samples of buccal mucosa, tongue and
      unstimulated saliva were studied in 107 subjects. Ten subjects had gingivitis, 18
      localized juvenile periodontitis, 45 rapidly progressive periodontitis and 32
      adult periodontitis. Two children suffered from prepubertal periodontitis.
      Heterogeneity tests for associations in different study populations yielded
      nonsignificant results. Mantel-Haenszel's common odds ratios were 52.9, 37.2 and
      19.8 for respective associations between pooled subgingival samples, and cheek,
      saliva and tongue samples. Significant McNemar's chi-square of 5.88, 11.25 and
      16.96 for respective associations pointed to secondary occurrence of A.
      actinomycetemcomitans in extracrevicular samples. Multiple linear regression
      yielded a significant influence of the number of deep periodontal pockets of 7 mm
      or more and a negative influence of the diagnosis "adult periodontitis" on the
      log-transformed number of colony-forming units of A. actinomycetemcomitans in
      samples from cheek mucosa in patients infected with the organism. Extracrevicular
      occurrence of A. actinomycetemcomitans seems to reflect total subgingival numbers
      of the organism. Especially sampling cheek mucosa appears to be a promising tool
      in the diagnosis of a periodontal infection with A. actinomycetemcomitans.

PMID- 8152835
TI  - Transmission of oral bacterial species between spouses.
AB  - The transmission of Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis and mutans streptococci was studied between 4 married couples who
      suffered from advanced periodontitis. Of the 20 couples investigated, the 4 in
      which both spouses harbored A. actinomycetemcomitans and P. gingivalis were
      chosen for the transmission study. Three of these couples also harbored mutans
      streptococci. A. actinomycetemcomitans isolates (8-24 per subject) and mutans
      streptococcal isolates (5-23 per subject) were serotyped by immunodiffusion
      technique. For ribotyping, chromosomal DNA from A. actinomycetemcomitans isolates
      (4-5 per subject) and mutans streptococcal isolates (4-11 per subject) was
      digested with restriction endonucleases ClaI or BglI and HindIII or SmaI,
      respectively. P. gingivalis isolates (2-15 per subject) were ribotyped by using
      ClaI, BglI and SmaI. The blotted restriction fragments were hybridized to the
      plasmid pKK3535, which contains the rRNA operon of the E. coli chromosome. The
      spouses in 2 couples shared the same sero- and ribotypes of A.
      actinomycetemcomitans and S. mutans. P. gingivalis ribotypes were identical in 2
      couples. The result suggests transmission of oral bacteria between spouses.

PMID- 8152836
TI  - The binding of delmopinol and chlorhexidine to Streptococcus mutans and
      Actinobacillus actinomycetemcomitans strains with varying degrees of surface
      hydrophobicity.
AB  - This study evaluated the binding of chlorhexidine and the new surface-active anti
      plaque agent delmopinol hydrochloride to Streptococcus mutans and Actinobacillus
      actinomycetemcomitans cells with various cell surface hydrophobicities. The
      influence of saliva concentration on the binding of these compounds was also
      investigated. The radiolabeled compounds were incubated with bacteria and the
      cells were recovered using a centrifugal filtering technique. Delmopinol had
      higher binding to the hydrophilic variant strains than to the hydrophobic parent
      strains; chlorhexidine had higher binding to hydrophobic than to hydrophilic A.
      actinomycetemcomitans strains and higher binding to hydrophilic than to
      hydrophobic S. mutans strains. The presence of salivary films decreased the
      binding of both compounds. Both delmopinol and chlorhexidine had stronger
      affinity to A. actinomycetemcomitans cells than to S. mutans cells. At equimolar
      concentrations, delmopinol had a lower binding to all strains tested than
      chlorhexidine. The high reversibility of the delmopinol binding might be related
      to a higher diffusion rate and solubility compared with that of chlorhexidine.
      The amphiphilicity of both molecules is an important feature in their retention
      to S. mutans and A. actinomycetemcomitans strains of varying hydrophobicities and
      could play an important role in the substantivity of delmopinol or chlorhexidine
      in the oral cavity.

PMID- 8152837
TI  - Factors influencing the growth and viability of Actinobacillus
      actinomycetemcomitans.
AB  - The metabolic requirements for the routine growth of Actinobacillus
      actinomycetemcomitans were investigated by the addition of nutrients to
      conventional bacteriological and tissue culture media. Commonly used tissue
      culture media required fetal bovine serum as an additive to sustain bacterial
      growth rates comparable to those obtained with bacteriological media. The
      addition of increasing concentrations of yeast extract to bacteriological medium
      increased the growth rate of several A. actinomycetemcomitans strains. In an
      attempt to identify the components of yeast extract that enhanced the growth of
      A. actinomycetemcomitans, a number of vitamins, essential and non-essential amino
      acids were tested for their role in promoting growth. The addition of L-cystine
      resulted in bacterial growth rates comparable to those with yeast extract.
      Thiamine increased the growth of several A. actinomycetemcomitans strains but did
      not result in growth rates comparable to those with yeast extract. The addition
      of physiological concentrations of steroid hormones to bacteriological medium
      enhanced the growth of A. actinomycetemcomitans. Additional iron compounds and
      fat-soluble vitamins had no influence on A. actinomycetemcomitans growth.
      However, the requirement of iron for bacterial growth remains unclear. The
      optimal pH range for growth of A. actinomycetemcomitans was between pH 7.0-8.0 in
      a medium containing 0.5-1% NaCl. Several interesting observations on the
      viability of A. actinomycetemcomitans were made. A rapid reduction of A.
      actinomycetemcomitans viability occurred following suspension in distilled water.
      The presence of the detergent Triton X-100 at concentrations above 2% (v/v) also
      decreased the viability of A. actinomycetemcomitans within 10 min.

PMID- 8152838
TI  - Survival in transport media of Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis and Prevotella intermedia in human subgingival samples.
AB  - The purpose of this study was to evaluate the survival in 3 transport media of 3
      suspected periodontal pathogens, Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis and Prevotella intermedia. Subgingival samples were
      taken from 10 patients with severe periodontitis, all harboring at least two of
      the above-mentioned species. The material was dispersed and aliquots were added
      to vials containing reduced transport fluid, reduced transport fluid containing
      10% Fildes extract, or viability-maintaining microbiostatic medium, anaerobically
      prepared (VMGA III). Viable counts were determined after 1, 2, 4, 24 and 48 h of
      storage at 4 degrees C or at room temperature. The results showed that, for up to
      4 h of storage, no significant differences existed for all parameters tested. A
      large increase of the total viable counts was found in VMGA III at room
      temperature after 24 and 48 h. This was due to an outgrowth of mainly
      streptococci. Incubation at 4 degrees C yielded often a significantly higher
      recovery compared to room temperature. After storage at room temperature, the
      tested bacteria were below detection level in some samples.

PMID- 8152839
TI  - A comparison of two transport media for saliva and subgingival samples.
AB  - This study has shown that microorganisms associated with caries (mutans
      streptococci, lactobacilli) and marginal periodontitis (Porphyromonas gingivalis,
      Prevotella intermedia and Actinobacillus actinomycetemcomitans) in pure culture
      can be stored in VMGA or reduced transport fluid and be recovered sufficiently
      after 24 h. Sufficient recovery after 24 h of mail transport was also obtained in
      37 saliva samples obtained from adults and 80 subgingival samples from a group of
      patients before and 3, 6 and 15 months after periodontal treatment. The samples
      transported in VMGA III showed in comparison to the samples transported in
      reduced transport fluid a higher recovery rate as well as a higher percentage of
      the total viable count for investigated anaerobic species. This was explained by
      the different composition of the two media and also by the gel consistency of
      VMGA III, which maintains a low redox-potential even during transport after
      transferring a sample into the medium. In a few samples aerobic bacteria
      increased in both media.

PMID- 8152840
TI  - Electron microscopy of phages in serotypes of Actinobacillus
      actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans, Actinobacillus ureae, Haemophilus
      aphrophilus, Haemophilus paraphrophilus, Haemophilus influenzae, Haemophilus
      parainfluenzae, Pasteurella haemolytica and Pasteurella multocida strains were
      examined by transmission electron microscopy for the presence of bacteriophages.
      Phages were detected in serotype a (SUNY 75) and e (UOH 1705) and in the fresh
      clinical isolates UOH Q1243 and UOH Q1247 of A. actinomycetemcomitans. Phages
      were not found in serotype b, c and d strains of A. actinomycetemcomitans, in the
      fresh clinical isolate UOH Q1244 of this species or in old strains (including
      reference strains) of related species from the Actinobacillus-Haemophilus
      Pasteurella group.

PMID- 8152841
TI  - Participation of an arginyl residue of insulin chain B in the inhibition of
      hemagglutination by Porphyromonas gingivalis.
AB  - Insulin chain B, containing each one arginyl and lysyl residue in its peptide
      chain, inhibited hemagglutination by Porphyromonas gingivalis. To determine the
      further inhibitory profile, chain B was digested into 4 fragments by protease,
      which was contained in the preparation of hemagglutinin from P. gingivalis.
      Identification of each fragment by the amino acid analysis revealed that the
      chain was cleaved at the carboxyl site of arginyl and/or lysyl residues, but one
      fragment contained citrulline instead of arginine at its carboxyl terminal. This
      citrulline might have originated from arginine by an arginine deiminase-like
      enzyme of P. gingivalis. Only one fragment that contained the arginyl residue
      exhibited inhibitory activity on hemagglutination, but it was considerably
      weakened compared with that of the intact chain B. The difference in the
      inhibitory activity seemed to depend on the position of an arginyl residue in the
      peptide; this was also confirmed using several derivatives of bradykinin. The
      present result suggests that the internal arginyl residue in a peptide chain may
      be critical for the inhibition of the hemagglutination by P. gingivalis.

PMID- 8152842
TI  - [The significance of the species classification of ixodid ticks and their hosts
      in the development of antitick immunity].
AB  - Larvae of Ixodes persulcatus and Hyalomma asiaticum were feeding permanently on
      hosts attacking them daily by groups of 5-20 ticks, and also fed by groups of 30
      40 and 100 ticks with the interval 20 days. The factor of the host species in the
      case of 1-st feeding of ticks did not influence significantly on the weight of
      engorged ticks and also on the percent of larvae, which had finished the feeding
      and moulted to nymphs. In the cases of 2-nd and 3-rd feedings the significant
      part of ticks died before the end of feeding, and engorged ticks had less weight
      and lower capability to moult. The rate of anti-tick resistance of hosts depends
      upon the species of the host and upon the number of ticks fed up. In the case of
      permanent feeding of larvae during 40 days the anti-tick resistance was low or
      completely absent.

PMID- 8152843
TI  - [The acquisition of resistance by laboratory mice to Amblyomma hebraeum
      (Ixodidae) larvae].
AB  - Repeated feedings of larval Amblyomma hebraeum ticks on laboratory mice results
      in strong decrease of engorged tick yield (from 65-73% after primary feeding to
      11% after secondary feeding). Laboratory mice differ essentially in this respect
      from rabbits and sheep which are unable to acquire the resistance (see Norval,
      1978) to larvae of this tick.

PMID- 8152844
TI  - [The factors that regulate oviposition in Leptopsylla segnis (Leptopsyllidae:
      Siphonaptera) fleas].
AB  - In the fleas Leptopsylla segnis settled on white mice the steady egg-laying took
      place under conditions including three factors--darkness, high relative air
      humidity (80-100%) and the "smell of host nest". The absence of anyone of these
      factors reduced an egg-production by 34-56%. The removal of the "smell" source
      coupled with substitution of high air humidity on low one (50-60%) interrupted
      the egg-laying almost completely inspite darkness or light. Owing such reaction
      on joint influence of the "smell of host nest" and air humidity the fleas are
      capable to interrupt and to recommence egg-laying depending on either the host is
      outside or in the nest.

PMID- 8152845
TI  - [The characteristics of the distribution of the causative agent of Lyme disease
      and of the behavior of infected ticks of the genus Ixodes].
AB  - It is demonstrated that in the regions, where Ixodes persulcatus and I. ricinus
      are sympatric, the incidence and prevalence of Borrelia burgdorferi among the
      latter tick species is higher. In areas, where the Ixodes persulcatus population
      infected with Borrelia were met, the percent of infected I. ricinus was 3-4 times
      more and the number of detection of Borrelia-infected specimens was 9 times
      higher than in the regions, where I. persulcatus was absent. The hypothesis is
      proposed, that the tick I. persulcatus is a carrier and source of the most
      virulent and acarotropic Borrelia form. It is stated, that the reaction of the
      Borrelia-infected Ixodes ticks (I. persulcatus and I. ricinus) on the plant odour
      is changed. It is supposed that such changed plant odour-dependent behavior would
      be able to be enhancer of the I. persulcatus--I. ricinus Borrelia exchange
      process.

PMID- 8152846
TI  - [The protein level in Bothriocephalus acheilognathi cestodes and their hosts,
      carp fingerlings, in experimental feeding and starving of the fish].

PMID- 8152848
TI  - Complete developmental cycle of Leishmania mexicana in axenic culture.
AB  - A complete developmental sequence of Leishmania mexicana has been produced in
      axenic culture for the first time. This was achieved by manipulation of media, pH
      and temperature conditions over a period of 16 days. All experiments were
      initiated with lesion amastigotes that were transformed to multiplicative
      promastigotes by culture in HOMEM, 10% foetal calf serum, pH 7.5, at 25 degrees
      C. Metacyclogenesis was induced by subpassage in Schneider's Drosophila medium,
      20% foetal calf serum, pH 5.5, and the resulting forms transformed to axenically
      growing amastigotes by subpassage in the same medium and raising the temperature
      to 32 degrees C. Parasites from each day were characterized with respect to their
      general morphology using light microscopy of Giemsa-stained smears, and
      biochemically by analysis of total protein content, proteinases, nucleases and
      secretory acid phosphatase. The results demonstrated that the three main stages
      identified--amastigotes, multiplicative promastigotes and metacyclic
      promastigotes--each exhibited the expected suite of biochemical properties.
      Further, the changes in morphology observed as the developmental sequence
      proceeded from stage to stage were accompanied by appropriate changes in
      biochemical properties. These results provide both useful biochemical markers and
      a culture system in which to examine the regulation of differentiation and
      transformation during the Leishmania life-cycle.

PMID- 8152847
TI  - [The ecological prerequisites for a worsening of the cercariasis situation in the
      cities of Russia (exemplified by the Moscow region)].
AB  - Conditions favouring the sharp increase of risk to be infected with cercariasis
      (caused by trematode cercariae Trichobilharzia ocellata Brumpt, 1931,
      Schistosomatidae) were examined in Moscow region (Russian Federation). Main
      factors of worsening the cercariasis situation are as follows. a) The increase of
      environment pollution by everyday wastages and the overgrowing with macrophytes
      in internal water basins of Moscow, that makes favourable conditions for the
      development of molluscs, which are intermediate hosts (mainly Lymnaea ovata and
      L. auricularia). b) The sharp increase of number of ducks (mainly mallard Anas
      platyrhyncos), which are final hosts, that is a result of bird escaping from
      farms (approximately in 60-70-th) and of high adaptation of these birds to city
      water basins. The detailed estimation of the cercariasis situation in 89 water
      basins of different types in Moscow and recreation zone was carried out. Examples
      of charting the zones with different risk degree of cercariasis infection are
      given. It is stated that at current time the cercariasis became a significant and
      widely distributed medical problem, which is most important in cities (including
      such large one as Moscow). Prophylaxis recommendations are proposed.

PMID- 8152849
TI  - Molecular systematics in the acanthocephalan genus Echinorhynchus (sensu lato) in
      northern Europe.
AB  - New biological species and high levels of inter- and intraspecific genetic
      divergence were discovered in an allozyme study of some North European members of
      the acanthocephalan genus Echinorhynchus (sensu lato), parasites of fish and
      malacostracan crustaceans. (i) A strong differentiation between the marine E.
      gadi and the fresh- and brackish-water E. salmonis (genetic identity I congruent
      to 0) supports a generic distinction between these taxa; however, the subdivision
      would not entirely concur with the concepts of Echinorhynchus (sensu stricto) and
      Metechinorhynchus suggested earlier. (ii) Samples of E. gadi from the Baltic,
      Norwegian and North Seas included three distinct, partially sympatric biological
      species (spp. I-III; I congruent to 0.5). (iii) E. bothniensis, previously only
      known from the northern Baltic Sea, represents a complex of freshwater taxa with
      an intermediate host relationship to the 'glacial relict' Mysis spp. and with a
      distributional and host analogy to the North American E. leidyi. A population in
      a northern lake in the Barents Sea basin is closely related to E. bothniensis of
      the Baltic area, but is probably specifically distinct; the divergence between
      these populations (I congruent to 0.6) is similar to that between their Mysis
      host species. (iv) Considerable intraspecific differentiation (FST = 0.25),
      probably reflecting post-glacial population bottlenecks, was found between Baltic
      and nearby lacustrine E. bothniensis, and between Atlantic and Baltic E. gadi sp.
      I.

PMID- 8152850
TI  - Density-dependent processes in the transmission of human onchocerciasis:
      intensity of microfilariae in the skin and their uptake by the simuliid host.
AB  - The transmission success of Onchocerca volvulus is thought to be influenced by a
      variety of regulatory or density-dependent processes that act at various points
      in the two-host life-cycle. This paper examines one component of the life-cycle,
      namely, the ingestion of microfilariae by the simuliid vector, to assess the
      relationship between intake of larvae and the density of parasites in the skin of
      the human host. Analysis is based on data from three areas in which
      onchocerciasis is endemic and includes published information as well as new data
      collected in field studies. The three areas are: Guatemala (Simulium ochraceum
      s.l.), West and Central Africa (savanna members of the S. damnosum complex), and
      South Venezuela (S. guianense). The data record experimental studies of parasite
      uptake by flies captured in the field and fed to repletion on locally infected
      subjects who harboured varying intensities of dermal microfilarial infection.
      Regression analyses of log transformed counts of parasite burdens ingested by the
      flies plotted against log transformed counts of microfilariae per mg of skin
      revealed little evidence for saturation in parasite uptake by the flies as the
      intensity in the human host increased. There was a positive and highly
      significant rank correlation between both variables for the three blackfly
      species. In an alternative analysis a model was fitted to data on prevalence of
      flies with ingested microfilariae (mff) versus dermal mean intensities. The model
      assumed an overdispersed distribution of the number of mff/fly and a given
      functional relationship between intake and skin load. The results of both
      approaches were consistent. It is concluded that parasite ingestion by the vector
      host is not strongly density dependent in the three geographical areas and ranges
      of dermal loads examined. It therefore appears that this transmission process is
      of reduced importance as a regulatory mechanism in the dynamics of parasite
      population growth.

PMID- 8152851
TI  - Elevated agglutination titres in plasma of Biomphalaria glabrata exposed to
      Echinostoma paraensei: characterization and functional relevance of a trematode
      induced response.
AB  - Production of elevated haemolymph agglutination titres by Biomphalaria glabrata
      following exposure to Echinostoma paraensei miracidia was investigated, to
      characterize this parasite-induced response and to understand its functional
      relevance. Both the dose of infection (1, 10 or 100 miracidia per snail) or the
      number of separate exposures to infection (between one and three, over a 4 or 8
      day interval) were varied, and assuming a threshold dosage (10 miracidia per
      snail or higher) was exceeded, titres of juvenile snails peaked at 8-16 times the
      values for unexposed control snails, regardless of the exposure regimen. Adult
      snails, which are relatively refractory to infection, have slightly higher
      resting titres than juveniles, but exhibit only a 2- to 4-fold increase in titre
      following exposure. Juveniles exposed to infection but lacking demonstrable
      infection had lower titres than snails with confirmed infections. Exposure to
      infection increased heterogeneity of plasma agglutinins and provoked production
      of unique specificities not found in unexposed snails. However, the overall
      pattern of agglutination responses for snails with successfully developed
      parasites did not differ from those in which parasite development was
      unsuccessful. Agglutinating activity was inhibitable by several different
      monosaccharides, although plasma from infected snails was relatively unaffected
      by N-acetyl-glucosamine or N-acetyl-galactosamine. Wounding of snails provoked no
      change in plasma agglutination activity. As the highest agglutination titres were
      produced in snails with successfully developing parasites and agglutinin
      composition did not differ between snails with successful or unsuccessful
      parasites, the functional relevance of the response remains enigmatic. The
      production of unique agglutinins following exposure deserves additional study.

PMID- 8152852
TI  - Effects of Schistosoma haematobium infection on reproductive success and male
      outcrossing ability in the simultaneous hermaphrodite, Bulinus truncatus
      (Gastropoda: Planorbidae).
AB  - The schistosome intermediate snail host, Bulinus truncatus (Mollusca:
      Planorbidae), has two reproductive (phally) morphs. Both aphallics and euphallics
      can self-fertilize, but aphallics cannot donate sperm because they do not develop
      a functional penis and prostate. This study investigated the interactions between
      phally and fitness consequences of Schistosoma haematobium infection in B.
      truncatus. Snails which developed patent infections produced 26% fewer eggs than
      controls and 35% fewer eggs than exposed snails which did not develop infections.
      This reduction was due to a lower lifetime production of egg masses and a smaller
      mean number of eggs/mass in infected snails relative to control or exposed
      snails. However, there was no evidence of increased mortality in infected snails.
      Contrary to reports of fecundity compensation in other intermediate host snails,
      egg production post-exposure during the pre-patent period did not increase
      relative to that of controls in either infected or exposed snails. Phally did not
      influence susceptibility to infection or length of the prepatent period.
      Furthermore, lifetime egg, egg mass and hatchling production, as well as mean
      eggs/mass and number of hatchlings reaching maturity, did not differ
      significantly between aphallics and euphallics within control of exposed
      experimental groups. However, within the infected group euphallics produced 38%
      fewer eggs, smaller egg masses, and fewer hatchlings reaching maturity than
      aphallics, supporting the prediction of a cost to the growth and maintenance of a
      full male tract. This cost was detectable only when snails were under the stress
      of infection. The proportion of euphallic offspring produced did not differ
      across experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152853
TI  - Schistosome extracts with heat shock factor activity revealed by the gel shift
      assay.
AB  - To understand the regulated expression of stage-specific genes of schistosomes,
      it is necessary to identify regulatory DNA elements and DNA-binding proteins that
      control the level of gene transcription. Here we describe the preparation of
      Schistosoma mansoni extracts with active transcription factors detected by the
      electrophoretic mobility shift assay (EMSA). We analysed the hsp70 system of S.
      mansoni because the promoters of the hsp70 gene contain two heat shock elements
      (HSE) that differ from the consensus sequence (CnnGAAnnTTCnnG) at one (HSEI) or
      three (HSEII) positions, and it is known that transcriptional activation of hsp70
      genes is mediated by interaction of HSE with the heat shock factor (HSP).
      Analyses of parasite extracts from different developmental stages demonstrate the
      presence of putative HSF that correlates with the pattern of hsp70 mRNA
      expression (cercariae-, schistosomula+, adult worms+). Cercarial extracts did not
      show binding of 32P-labelled HSEI or HSEII. Extracts of schistosomula and of
      adult worms kept at 37 or 42 degrees C showed binding of HSEI but not HSEII. The
      specificity of HSEI-HSF complex formation was ascertained by inhibition
      experiments. The EMSA experiments and structural features of the hsp70 promoter
      indicate that HSEI is the major DNA element responsible for transcriptional
      activation of the hsp70 gene, while the HSEII may be a redundant sequence with
      minor (if any) regulatory function. The extracts reported here can be used to
      study transcriptional control of other schistosome genes.

PMID- 8152854
TI  - Characterization of a HMG2-like protein from Schistosoma mansoni.
AB  - An HMG2-like protein was purified from nuclear extracts of adult Schistosoma
      mansoni. Investigation of the amino acid composition of the schistosome HMG2-like
      protein showed that glutamic acid, glycine, aspartic acid and lysine were the
      most abundant. Carbohydrate analysis showed that the HMG2-like protein presented
      a low degree of glycosylation, galactose or glucose being the major
      monosaccharide constituent. Incubation of live schistosomes with 32P followed by
      isolation of nuclear proteins showed that the HMG-2 like protein could be
      phosphorylated. Partial sequence analysis of cyanogen bromide peptides revealed
      the occurrence of a phosphorylation consensus motif. The schistosome HMG2-like
      protein was found to bind preferentially to single-stranded DNA. The results
      suggest that the major non-histone S. mansoni nuclear protein belongs to the HMG
      family.

PMID- 8152855
TI  - Genomic and phenotypic diversity of Tunisian Theileria annulata isolates.
AB  - This study describes polymorphism in Theileria annulata, an intracellular
      protozoan parasite of bovine leucocytes and red blood cells. Fifty-three
      different stocks of T. annulata, isolated from 17 sites (districts) in Tunisia,
      have been characterized by anti-parasite monoclonal antibody (MAb) reactivity,
      glucose phosphate isomerase (GPI) isoenzyme electrophoresis, and Southern
      blotting with two genomic DNA probes. These appears to be considerable diversity
      amongst T. annulata stocks from Tunisia, no two isolates being identical, even
      those from animals on the same farm. Two distinct antigenic populations were
      detected by MAb 7E7. They were defined by negative and positive cells in the
      indirect fluorescent antibody test. The percentage of positive cells in different
      isolates ranged between 0 and 100%. The population variation seen by GPI analysis
      and DNA probes was greater; 7 different GPI phenotypes were identified amongst
      the stocks studied, while DNA probes T. annulata Tunis (TaT) 17 and 21 detected
      up to 5 different variants. The majority of isolates were shown to contain more
      than one parasite population, the number of variants per isolate ranging from 1
      to 4. No correlation between particular parasite phenotypes or genotypes and
      their geographical site of isolation was observed. Selection of parasite
      populations in vivo and in vitro is also discussed.

PMID- 8152856
TI  - Heligmosomoides polygyrus and Trypanosoma congolense infections in mice: a
      laboratory model for concurrent gastrointestinal nematode and trypanosome
      infections.
AB  - A murine model using Heligmosomoides polygyrus and Trypanosoma congolense has
      been developed for studying the effects of concurrent chronic gastrointestinal
      nematode and trypanosome infections. Female outbred mice were infected either
      with 500 infective larvae (L3) of H. polygyrus or with 10(4) bloodstream forms of
      T. congolense or both. In concurrent infections, animals were dosed with both
      parasites simultaneously or the trypanosomes were injected 5 or 10 days after the
      mice were infected with the nematode. The course of infection was monitored by
      routine parasitological and immunological techniques for 30 days after the H.
      polygyrus infection. Concurrently infected mice were severely compromised, except
      when T. congolense was superimposed on a 10-day-old (adult) H. polygyrus
      infection. In H. polygyrus-infected mice, simultaneous or subsequent infection
      with trypanosomes did not markedly influence worm establishment or fecundity, but
      the female worms were slightly stunted. Surviving mice displayed a markedly
      reduced antibody response to H. polygyrus antigens and a slightly reduced
      antibody response to T. congolense antigens.

PMID- 8152857
TI  - Interactions between infections with Eimeria spp. and Trichinella spiralis in
      inbred mice.
AB  - Parasitological and immunological interactions between Eimeria vermiformis or E.
      pragensis and Trichinella spiralis were investigated during concurrent infections
      in NIH, BALB/c and B10.G inbred mice. The establishment of T. spiralis was
      unaffected by the presence of either coccidium, but expulsion of adult worms was
      delayed significantly in mice infected with E. vermiformis; E. pragensis did not
      have this effect. Replication of E. vermiformis was enhanced in concurrent
      infections with T. spiralis, but that of E. pragensis was reduced. Specific
      immune responses to each parasite were unaffected in mice infected with T.
      spiralis and E. pragensis, but levels of some responses were reduced when T.
      spiralis and E. vermiformis were combined. Thus both in vitro antigen-induced
      proliferation of mesenteric lymph node cells (MLNC) and intestinal mastocytosis
      were lower than in singly infected mice. Mitogen (Con A) responsiveness of MLNC
      was not affected in mice infected with T. spiralis and E. vermiformis, and cells
      from these mice were capable of transferring protective immunity to the nematode
      in naive recipients. Injection of monoclonal antibody to interferon gamma, a
      major component of the cytokine response to E. vermiformis, did not prevent delay
      of worm expulsion in concurrent infections. The results are discussed in terms of
      possible interactions between the T helper cell subsets or the inflammatory
      components of the responses induced by each parasite.

PMID- 8152858
TI  - Genetic relatedness as a determinant of predisposition to Ascaris lumbricoides
      and Trichuris trichiura infection.
AB  - The present study examines the role of host genetics in predisposition to Ascaris
      lumbricoides and Trichuris trichiura infection, by comparing the associations
      between age-standardized infection intensities of parents and their children
      (genetically related), with age-standardized infection intensities of parents
      alone (not related), within families previously demonstrated to exhibit familial
      predisposition. The lack of a consistent trend in infection intensity
      associations within families, in particular the lack of a stronger association
      between parents and their children than between unrelated parents, suggests that
      host genetic factors are not a major determinant of infection status. If there is
      a genetic basis for predisposition, then the data suggest that the effects of
      this genetic basis are overwhelmed by other, environmental or behavioural
      features of the family household.

PMID- 8152859
TI  - Characterization of identifiable neurones in the head ganglia of the parasitic
      nematode Ascaris suum: a comparison with central neurones of Caenorhabditis
      elegans.
AB  - Intracellular recordings have been made from neurones in the head ganglia of
      Ascaris. The neurones had low resting membrane potentials of -21 +/- 9 mV (n =
      78) and a relatively high input resistance (e.g. 25 M omega for a 100 microns
      cell). In all cases the intracellular location of the recording electrode was
      verified by injection of the fluorescent marker, 5,6-carboxyfluorescein (CBXF).
      To ascertain whether or not the low membrane potential was due to impalement
      damage, the same neurone was recorded from using two microelectrodes. The
      membrane potential following the first impalement by a 20 M omega 3 M KCl
      electrode was -38 mV and following the second impalement by a 80 M omega CBXF
      (for subsequent intracellular labelling) electrode was decreased to -34 mV. Input
      resistance of these cells was estimated using both single and two electrode
      intracellular recording techniques and in both cases yielded a relatively high
      value for the size of cell (e.g. 25 M omega for a 100 microns cell). Neurones
      labelled by intracellular injection of the fluorescent marker 5,6
      carboxyfluorescein were morphologically simple and lacked extensive
      arborizations. The dorsal ganglion is a discrete structure consisting of only 3
      neurones. Here we compare the morphological properties of these neurones to those
      described in the dorsal ganglion of Caenorhabditis elegans. The whole mount
      preparation of Ascaris ganglia thus provides a useful model to study the
      functional properties of neurones in nematode central nervous system and presents
      the possibility to assess central sites of action for anthelmintics.

PMID- 8152860
TI  - Epidemiology and prevention of pediatric traumatic brain injury.

PMID- 8152861
TI  - Acute care management of closed head injury in childhood.

PMID- 8152862
TI  - Pediatric traumatic brain injury: prognosis and rehabilitation.

PMID- 8152863
TI  - Family functioning following pediatric traumatic brain injury.

PMID- 8152864
TI  - Educational implications of traumatic brain injury.

PMID- 8152865
TI  - A pediatrician's view. Why deaths from head injuries are on the decline.

PMID- 8152866
TI  - Blood flow velocities in the cerebral arteries and descending aorta in small-for
      dates infants.
AB  - Resistive indices (RI) in the anterior cerebral artery (ACA), basilar artery
      (BA), middle cerebral artery (MCA) and descending aorta (DA) were obtained in 15
      small-for-dates (SFD) infants who were, growth retarded because of maternal
      pregnancy-induced hypertension and in 20 appropriate-for-dates (AFD) infants
      matched for gestational age between 24 h and 48 h after birth. The RIs in the
      MCA, ACA and BA were significantly lower, while the RI in the DA was
      significantly higher, in the SFD infants than in the AFD infants. These changes
      in RIs in the SFD infants might be similar to the "brain sparing" effect as
      reported in growth-retarded fetuses.

PMID- 8152867
TI  - Doppler sonographic detection of increased flow velocities in the celiac trunk
      and superior mesenteric artery in infants with necrotizing enterocolitis.
AB  - Fourteen infants (gestational age 28.4 +/- 4.4 weeks; birth weight 1170 +/- 910
      g) with clinical and radiological signs of necrotizing enterocolitis (NEC) were
      investigated by pulsed Doppler sonography. Pulsed Doppler recordings were
      performed in the celiac trunk and the superior mesenteric artery at an age of 15
      +/- 10 days. The peak systolic, end-systolic, end-diastolic and time average
      velocities were measured and compared with the flow velocities of a healthy
      control group. Infants with NEC showed a significant increase in peak systolic
      and time average velocity within the celiac trunk and the superior mesenteric
      artery in comparison with healthy infants.

PMID- 8152868
TI  - Postoperative MRI evaluation of anorectal malformations with clinical
      correlation.
AB  - Sixteen postoperative patients with anorectal malformation were evaluated by MRI,
      and the results compared with the clinical assessment. Patients were classified
      into three groups--good (group 1, n = 10), fair (group 2, n = 3) and poor (group
      3, n = 3)--on the basis of Kelly's clinical score of incontinence. The degree of
      development of the puborectalis and external sphincter muscles and the levator
      hammock was evaluated on MRI in comparison with patients without anorectal
      disease. The proportions of fair or poor development of the muscles were 37% in
      group 1,22% in group 2 and 67% in group 3. Although fair or poor development of
      the muscles was seen more frequently in group 3, there was no statistically
      significant difference between groups. However, poorly developed muscles were
      seen only in patients with fair or poor clinical scores. The difference in the
      anorectal angle measured on sagittal MRI images between patients in group 1 and
      groups 2 or 3 was significant. Our study indicates that MRI evaluation based
      solely on muscle development can be misleading, and measurement of the anorectal
      angle should be included in the MRI evaluation.

PMID- 8152869
TI  - Hypersensitivity reaction to single contrast barium meal studies in children.
AB  - We report two children who developed hypersensitivity reactions of varying
      severity following barium meal examination, the more severe of which was
      associated with documented severe food allergy. For children with this risk
      factor, contrast studies should be performed only where facilities and personnel
      are available for immediate resuscitation of all sizes of child. For children
      such as these, consideration should be given to the use of pure barium sulphate.

PMID- 8152870
TI  - Barium enema findings in a case of Langerhans cell histiocytosis involving the
      colon.
AB  - Gastrointestinal (GI) tract involvement in Langerhans cell histiocytosis is
      probably not uncommon [1,2], but reports of radiologic findings have been limited
      to the small intestine and mesenteric lymph nodes [3-5]. We report a 16-month-old
      child with known Langerhans cell histiocytosis, who was found to have mucosal
      irregularities of the colon as seen on air contrast barium enema, and was
      subsequently found to have diffuse involvement of the colon histologically
      confirmed by multiple biopsies.

PMID- 8152871
TI  - The low frequency of reflux in Jamaican children.
AB  - Fifty consecutive micturating cystourethrograms (MCUG) performed at the UHWI
      between June 1989 and December 1991 were reviewed. There were forty boys and ten
      girls. Infants under the age of one year accounted for 58%. Urinary tract
      infection was the commonest presenting feature (72%), voiding difficulties (10%)
      and associated malformations (14%) were the other reasons for doing the MCUG.
      Only 10% of the children revealed vesico-ureteral reflux (VUR) which supports the
      view that reflux is less common in the noncaucasian population. In our
      population, the yield from MCUG is low. However, when detected, the reflux was of
      significant degree as to warrant active therapy. All but one of the VU refluxes
      diagnosed by MCUG had ultrasonographic abnormalities. Black children with single
      urinary infections have a low likelihood of VUR. A clear history of
      pyelonephritis and abnormalities on ultrasound or radionuclide cystogram may be
      used as criteria to select those in whom MCUG will be useful.

PMID- 8152872
TI  - The claustrum on MRI: normal anatomy, and the bright claustrum as a new sign in
      Wilson's disease.
AB  - One hundred MRI examinations of normal subjects obtained at 0.5 T were studied in
      an effort to evaluate the claustrum and to establish a control group for patients
      with Wilson's disease. The claustrum was detectable unilaterally or bilaterally
      in 40 out of 100 subjects (40%) on spin-echo long TR (proton density and T2
      weighted) MR images as a thin sheet of grey matter enclosed by low signal white
      matter of the external and extreme capsules. Spin-echo T1-weighted images were
      negative for the claustrum, however, it was identifiable in 12 out of 25 subjects
      (48%) studied utilizing the inversion recovery pulse sequence. In addition, eight
      patients with clinically established diagnoses of Wilson's disease were
      evaluated. The claustrum was normal (invisible) in four neurologically
      asymptomatic Wilson's disease patients, however, in 75% (n = 3) of the four
      neurologically symptomatic patients it was bilaterally thickened and bright on
      long-TR MR images. The bright claustrum appears to be a new sign in Wilson's
      disease.

PMID- 8152873
TI  - Metastatic choriocarcinoma in an infant: imaging appearance.
AB  - Metastatic choriocarcinoma is unusual in infancy and considered to be due to
      metastases from the placenta. Only fifteen cases have been previously reported.
      We present an unusual case of hepatic, pulmonary, and axillary lymph node
      metastases from choriocarcinoma in a 3-month-old female. Several of the lesions
      had large vascular channels identified by computed tomography and sonography with
      color and duplex Doppler.

PMID- 8152874
TI  - Prenatal diagnosis and management of congenital volvulus.
AB  - We present a case of a twin gestation in which one twin developed a complex
      abdominal mass and signs of small bowel obstruction. Following delivery, an
      exploratory laparotomy revealed a meconium pseudocyst and midgut volvulus. While
      the infant survived, a large portion of small bowel was atretic, resulting in
      short bowel syndrome. The prenatal diagnosis of volvulus is rare. When volvulus
      is present, the risk of bowel infarction is high, with variable perinatal
      outcome.

PMID- 8152875
TI  - Malrotation in twins: a rare occurrence.
AB  - Although malrotation is commonly found in infants with intestinal obstruction,
      the presence of malrotation in twins is rare. We report a set of twins who each
      had malrotation and non-bilious vomiting on the first day of life.

PMID- 8152876
TI  - Cystic sonographic appearance of extralobar pulmonary sequestration.
AB  - A cystic fetal chest mass showing spontaneous improvement in utero is described.
      This mass was shown to be an extralobar pulmonary sequestration with associated
      cystic adenomatoid malformation type 2.

PMID- 8152877
TI  - Intervertebral disc herniations (limbus vertebrae) in pediatric patients: report
      of 15 cases.
AB  - A revision of 15 cases of back pain and radiological features characteristic of
      anterior or posterior limbus vertebrae is presented. We comment on the
      radiological findings observed in the various imaging studies performed
      (conventional radiology, CT and MRI), which were attributed to the herniation of
      disc material into the vertebral body. In three patients who were followed up 12
      years after the diagnosis, the initial roentgenograms of limbus vertebrae
      progressed in adult hood into radiological images characteristic of Schmorl's
      hernia as a sequela.

PMID- 8152878
TI  - Sponastrime dysplasia: report on two siblings with metal retardation.
AB  - We report on two sisters in the third family affected with Sponastrime dysplasia.
      The clinical and radiological features are presented. The two patients showed
      severe mental retardation. The pattern of inheritance of this rare dysplasia is
      discussed.

PMID- 8152879
TI  - Fetal alcohol syndrome and bilateral tibial exostoses. A case report.
AB  - Maternal exposure to alcohol during pregnancy has been associated with fetal
      malformations referred to as the fetal alcohol syndrome. This paper describes,
      for the first time, the presence of bilateral tibial exostoses in a child with
      FAS.

PMID- 8152880
TI  - Restrictive dermopathy.
AB  - Restrictive dermopathy is an inherited syndrome characterized clinically by
      severe growth retardation, abnormal skin, characteristic facies, and multiple
      congenital contractures. Distinctive radiologic features include deficient
      mineralization of the clavicles and the skull, overtubulation and frequent
      modeling defects of the long bones, and occasional abnormalities of the ribs and
      scapulae.

PMID- 8152881
TI  - Myxoid liposarcoma of the porta hepatis in childhood.
AB  - Liposarcoma in childhood is rare. A case of a myxoid liposarcoma arising at the
      porta hepatis is reported in a 3-year-old boy with initial favourable response to
      surgery combined with radio- and chemotherapy. Fatal recurrence occurred at age
      15 years. The radiological and sonographic findings of liposarcomas are reviewed.

PMID- 8152882
TI  - Primary rhabdomyosarcoma of the diaphragm: an unusual cause of adolescent pseudo
      achalasia.
AB  - We report an adolescent male who presented with progressive dysphagia. Barium
      examination and upper endoscopy revealed the presence of a smoothly tapered
      stricture at the lower end of a dilated oesophagus typical of achalasia. Further
      evaluation by computed tomography (CT), demonstrated the presence of a bulky
      infiltrating diaphragmatic mass encasing the lower oesophagus. CT guided biopsy
      of the mass and subsequent post mortem examination revealed the presence of a
      primary rhabdomyosarcoma of the diaphragm encasing the lower oesophagus. A
      diagnosis of pseudo-achalasia secondary to a primary diaphragmatic tumour was
      made.

PMID- 8152883
TI  - Inflammatory pseudotumour of the lung. A case report.
AB  - Inflammatory pseudotumours are rare benign pulmonary lesions varying in
      localization, size and clinical features, and can pose difficulties with
      differential diagnosis. The radiological appearance is unspecific and the
      histopathological picture polymorphous. The aetiology is unknown. A case of
      intrathoracic plasma cell granuloma is reported.

PMID- 8152884
TI  - Pulmonary paragonimiasis simulating lung abscess in a 9-year-old: CT findings.
AB  - We present the CT findings of pulmonary paragonimiasis in a 9-year-old girl. It
      appeared as a large cystic mass with an air-fluid level and simulated a lung
      abscess. Communication with a segmental bronchus was demonstrated well on a CT
      scan obtained after aspiration.

PMID- 8152885
TI  - Acute epidural haematoma with hypodense bubbles on CT: a sign of dural sinus tear
      or solely fresh bleeding?
AB  - Acute epidural haematomas are less commonly seen in children than in adults, and
      are even rarer in infants. On CT these haematomas sometimes show hypodense
      bubbles, an appearance the interpretation of which has been a matter of
      controversy. Identification of the origin of the bleeding--whether from torn
      dural sinuses or transected meningeal vessels--is neurosurgically significant.
      This report presents the CT study of an infant with an acute epidural haematoma
      containing hypodense bubbles which occurred due to fresh bleeding from injured
      meningeal vessels.

PMID- 8152886
TI  - Women and mental health.

PMID- 8152887
TI  - Childbearing.

PMID- 8152888
TI  - Midlife women's health: there's more to it than menopause.

PMID- 8152889
TI  - Women and weight control.

PMID- 8152890
TI  - Research on alcohol and drug use among women: a review and update.

PMID- 8152891
TI  - Women's cardiovascular health.

PMID- 8152893
TI  - Sexually transmitted diseases.

PMID- 8152892
TI  - Occupational issues in women's health.

PMID- 8152894
TI  - Acute care of women.

PMID- 8152895
TI  - Women's sexuality.

PMID- 8152896
TI  - Contraception.

PMID- 8152897
TI  - [Utilization of transfusions in the hematology clinic. Recommendations of the
      Evaluation Commission of the French College of Hematologists for transfusion
      support in the treatment of acute leukemia in therapeutic aplasia].

PMID- 8152898
TI  - Results of EMATAP: a double-blind placebo-controlled multicentre trial of
      ticlopidine in patients with peripheral arterial disease.
AB  - EMATAP, a randomized stratified, placebo-controlled double-blind multicentre
      trial was performed in Argentina in order to confirm the effect of ticlopidine in
      the prevention of thrombotic events in patients with intermittent claudication.
      Twenty-one clinical centres enrolled 615 patients, 304 (88 diabetic and 216 non
      diabetic) were assigned to the ticlopidine group and 311 (95 diabetic and 216 non
      diabetic) to the placebo group. Treatments were given for 24 weeks. The baseline
      characteristics were identical in both groups. The compliance was good and only
      34 patients (17 in each group) did not reach the last visit. Their status however
      was checked and known at that time and according to the protocol, there was no
      patient lost to follow-up. Twenty-five patients experienced a first event during
      the follow-up period and the results show a very dramatic reduction of events in
      the ticlopidine group (5 vs 20), the difference being highly significant (p =
      0.002) in intention-to-treat analysis. If we consider the subgrouping of outcome
      events: sudden deaths, myocardial infarctions and strokes on the one hand,
      vascular surgery on the other hand, a significant reduction is found in the
      ticlopidine group. Taking into account the total deaths plus non-fatal events (9
      vs 21), the results were also significant (p = 0.027). These above results
      therefore demonstrate a consistent reduction in all outcome events. As regard
      side effects there were fewer gastro-intestinal disturbances and skin reactions
      than seen in North American trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8152899
TI  - Performance evaluation of the haematological analyser Cell-Dyn 3000 (Abbott).
AB  - The Abbott Cell Dyn (CD) 3000 is an automatic analyser, designed to give a
      complete blood count (CBC) and white blood cell differential (WBCD) by 4 angle
      diffraction analysis. This instrument was evaluated by comparison of results
      obtained with those obtained from a Technicon H1 analyser and by microscopic
      examination. Technical performances with regard to reproducibility, linearity and
      carryover was acceptable and in normal samples there was close correlation with
      the optical method (R > 0.9) for neutrophils (NE), lymphocytes (LY) and
      eosinophils (EO). Correlation for monocytes (MO) and basophils (BA) was poorer
      but without clinical consequences. Significant thresholds for immature
      granulocyte (IG) and variant lymphocyte (VL) flags were determined and using
      these thresholds the false positive rate was reduced to 7%. In haematological
      diseases, no false negatives were observed as all samples were flagged. However,
      since no case of acute lymphoblastic leukaemia (ALL) was studied, the detection
      of lymphoblasts which is known to present difficulties for analysers remains to
      be evaluated. Blasts in acute myeloblastic leukaemia (AML) and hairy cells were
      recognised, while in chronic lymphocytic leukaemia (CLL) it was possible to
      define 3 groups according to the flags released. The CD appears to be a
      satisfactory analyser for use in general or haematological laboratories
      performing a large number of WBCD per day.

PMID- 8152900
TI  - Cutaneous findings in hairy cell leukemia. Review of 84 cases.
AB  - The authors of this paper present a retrospective analysis of 84 cases of hairy
      cell leukaemia diagnosed over the past ten years in two haematology departments.
      Cutaneous manifestations are noted on 47 occasions, 58% of infectious origin with
      60% of these infections due to bacterial agents, results which are in relatively
      close accord with those of the Mayo Clinic. Since no cases of necrotic angeitis
      or neutrophilic dermatosis are reported, the considerable number of publications
      concerning these affections give a poor indication of their rarity. Prospective
      studies will be required to evaluate the incidence of spinocellular carcinoma and
      melanoma, while specific lesions are only infrequently encountered and do not
      appear to bear the same unfavourable prognosis as in other haemopathia.

PMID- 8152901
TI  - A new chronometric assay to determine plasma antifactor Xa activity which is
      insensitive to the antithrombin activity of low molecular weight heparins.
AB  - Some commercially available chronometric assays are influenced by the residual
      antithrombin activity of low molecular weight heparins (LMWH) and they
      underestimate the ex vivo anti Xa activity. We have evaluated a new kit (Staclot
      Heparin) highly specific for the anti Xa activity of LMWH. A comparison with the
      results given by a reference chromogenic method (Stachrom-Heparin) indicates a
      very good correlation between the 2 assays (r = 0.95, n = 59). This new assay is
      not influenced by vitamin K antagonist treatments. Clinical biologists now have
      the possibility of determining the anti Xa activity generated by LMWH easily and
      accurately, using a chronometric assay.

PMID- 8152902
TI  - Haemoglobinopathies C and S in the Dogons.
AB  - The distribution of haemoglobins C and S was studied in a population of caste and
      non caste Dogons living in villages located on the plateau and scree regions in
      the Sangha department of Mali. Results showed a 15.77% prevalence of
      haemoglobinopathy AC. Haemoglobin C was found in both plateau and scree villages
      and equally among caste and non caste Dogons, while the homozygous form CC was
      absent in non Dogons. The prevalence of haemoglobinopathy AS was extremely low
      with a calculated frequency of 3.05%, allele S being restricted to areas where
      one is likely to encounter populations other than the Dogon people. Homozygotes
      SS were not detected and the phenotype SC was only rarely identified. An overall
      analysis of these data not only suggests that allele S is of recent introduction
      in the Dogons but also raises the question as to whether their origin is not the
      voltaic rather than the Manding plateau. Studies of marriage patterns and
      haplotypes currently in progress should enable resolution of this controversy.

PMID- 8152903
TI  - Hypereosinophilic syndrome in childhood: trisomy 8 and transformation to mixed
      acute leukaemia.
AB  - We report a pediatric case of hypereosinophilic syndrome (HES) with trisomy 8 and
      terminal blastic transformation to mixed acute leukaemia. Literature cases are
      reviewed, with emphasis on prognostic factors to differentiating "benign" from
      malignant HES.

PMID- 8152904
TI  - A case of IgA deficiency with anti-IgA antibodies and autoimmune
      thrombocytopenia.
AB  - The case of a young woman with autoimmune thrombocytopenia, complete IgA
      deficiency and anti-IgA antibodies is presented and the role of the AH 8-1
      supratype (HLA B8, DR3) is discussed. Such an association necessitates use of IgA
      free blood products in order to avoid anaphylactic reactions.

PMID- 8152905
TI  - Multiple elements in human beta-globin locus control region 5' HS 2 are involved
      in enhancer activity and position-independent, transgene expression.
AB  - The human beta-globin Locus Control Region (LCR) has two important activities.
      First, the LCR opens a 200 kb chromosomal domain containing the human epsilon-,
      gamma- and beta-globin genes and, secondly, these sequences function as a
      powerful enhancer of epsilon-, gamma- and beta-globin gene expression. Erythroid
      specific, DNase I hypersensitive sites (HS) mark sequences that are critical for
      LCR activity. Previous experiments demonstrated that a 1.9 kb fragment containing
      the 5' HS 2 site confers position-independent expression in transgenic mice and
      enhances human beta-globin gene expression 100-fold. Further analysis of this
      region demonstrates that multiple sequences are required for maximal enhancer
      activity; deletion of SP1, NF-E2, GATA-1 or USF binding sites significantly
      decrease beta-globin gene expression. In contrast, no single site is required for
      position-independent transgene expression; all mice with site-specific mutations
      in 5' HS 2 express human beta-globin mRNA regardless of the site of transgene
      integration. Apparently, multiple combinations of protein binding sites in 5' HS
      2 are sufficient to prevent chromosomal position effects that inhibit transgene
      expression.

PMID- 8152906
TI  - Introduction of wild-type p53 in a human ovarian cancer cell line not expressing
      endogenous p53.
AB  - Utilizing a temperature sensitive p53 mutant (pLTRp53cGval135) which expresses
      mutant p53 at 37 degrees C and a wild-type like p53 at 32 degrees C, we
      transfected a human ovarian cancer cell line (SKOV3) which does not express
      endogenous p53. Among the different clones obtained, we selected three clones.
      Two were obtained from simultaneous transfection of p53 and neomycin resistance
      expression plasmids (SK23a and SK9), the other was obtained from transfection
      experiments utilizing the neomycin resistance gene only (SKN). Introduction of
      mutant p53 did not alter the morphology or growth characteristics of this ovarian
      cancer cell line. Upon shifting to the permissive temperature, a dramatic change
      in morphology and growth rate was observed in SK23a and SK9 cells that is
      associated with the presence of a wild-type like p53. SKN and SKOV3 cells
      maintained at 32 degrees C did not change morphology and only slightly reduced
      proliferation. Both SK23a and SK9 cells did not show evidence of apoptosis when
      measured up to 72 hours of maintenance at 32 degrees C. In contrast to what
      observed in other cell lines, SK23a and SK9 cells maintained at 32 degrees C were
      not blocked in G1, but they were accumulated in G2-M. This accumulation was
      transient and could be due either to a blockade or to a delay in the G2
      progression. No down-regulation of c-myc was observed in p53 expressing clones
      when shifted to the permissive temperature. In these conditions gadd45 mRNA
      expression was highly stimulated in SK9 and SK23a cells but not in SKN cells. In
      both clones Gas1 mRNA was not detected either at 37 degrees C or 32 degrees C.
      This system represents a new and useful model for studying the effect of the
      absence of p53 (SKOV3 or SKN), presence of mutated p53 (SK23a and SK9 kept at 37
      degrees C) or wild type p53 (SK23a and SK9 kept at 32 degrees C) on the mechanism
      of response of cancer cells to DNA damaging agents.

PMID- 8152907
TI  - A novel bipartite splicing enhancer modulates the differential processing of the
      human fibronectin EDA exon.
AB  - EDA is a facultative type III homology of human fibronectin encoded by an
      alternative spliced exon. The EDA+ and EDA- mRNA forms show a cell type specific
      distribution with their relative proportion varying during development, aging and
      oncogenic transformation. We have previously demonstrated that an 81 bp
      nucleotide sequence within the exon itself is essential for differential RNA
      processing. Fine mapping of cis acting elements within this region has been
      carried out to identify possible target sites for the modulation of alternative
      splicing. There are at least two short nucleotide sequences involved. Element A
      (GAAGAAGA) is a positive modulator for the recognition of the exon, its deletion
      results in constitutive exclusion of the EDA exon. Element B (CAAGG) is a
      negative modulator for exon recognition, its deletion results in constitutive
      inclusion of the EDA exon. This bipartite structure of the splicing enhancer is a
      novel feature of the mammalian exons.

PMID- 8152908
TI  - Intermolecular disintegration and intramolecular strand transfer activities of
      wild-type and mutant HIV-1 integrase.
AB  - We report the activities of HIV integrase protein on a novel DNA substrate,
      consisting of a pair of gapped duplex molecules. Integrase catalyzed an
      intermolecular disintegration reaction that requires positioning of a pair of the
      gapped duplexes in a configuration that resembles the intgration intermediate.
      However, the major reaction resulted from an intramolecular reaction involving a
      single gapped duplex, giving rise to a hairpin. Surprisingly, a deletion mutant
      of integrase that lacks both the amino and carboxyl terminal regions still
      catalyzed the intermolecular disintegration reaction, but supported only a very
      low level of the intramolecular reaction. The central core region of integrase is
      therefore sufficient to both bind the gapped duplex DNA and juxtapose a pair of
      such molecules through protein-protein interactions. We suggest that the branched
      DNA structures of the previously reported disintegration substrate, and the
      intermolecular disintegration substrate described here, assist in stabilizing
      protein-protein interactions that otherwise require the amino and carboxy
      terminal regions of integrase.

PMID- 8152909
TI  - DNA looping by the HMG-box domains of HMG1 and modulation of DNA binding by the
      acidic C-terminal domain.
AB  - We have compared HMG1 with the product of tryptic removal of its acidic C
      terminal domain termed HMG3, which contains two 'HMG-box' DNA-binding domains.
      (i) HMG3 has a higher affinity for DNA than HMG1. (ii) Both HMG1 and HMG3
      supercoil circular DNA in the presence of topoisomerase I. Supercoiling by HMG3
      is the same at approximately 50 mM and approximately 150 mM ionic strength, as is
      its affinity for DNA, whereas supercoiling by HMG1 is less at 150 mM than at 50
      mM ionic strength although its affinity for DNA is unchanged, showing that the
      acidic C-terminal tail represses supercoiling at the higher ionic strength. (iii)
      Electron microscopy shows that HMG3 at a low protein:DNA input ratio (1:1 w/w; r
      = 1), and HMG1 at a 6-fold higher ratio, cause looping of relaxed circular DNA at
      150 mM ionic strength. Oligomeric protein 'beads' are apparent at the bases of
      the loops and at cross-overs of DNA duplexes. (iv) HMG3 at high input ratios (r =
      6), but not HMG1, causes DNA compaction without distortion of the B-form. The two
      HMG-box domains of HMG1 are thus capable of manipulating DNA by looping,
      compaction and changes in topology. The acidic C-tail down-regulates these
      effects by modulation of the DNA-binding properties.

PMID- 8152910
TI  - The conserved 3'-flanking sequence, AATGGAAATG, of the wheat histone H3 gene is
      necessary for the accurate 3'-end formation of mRNA.
AB  - We examined the 3'-flanking regions required for accurate 3'-end formation of
      wheat histone H3 mRNA using gene expression in transformed sunflower cells. The
      introduction of mutations into the conserved sequence AATGGAAATG in the 3'
      flanking region of plant histone genes, located 22 bp upstream from the
      polyadenylation site of the wheat H3 gene (TH012), completely abolished the 3'
      end formation of mRNA at the authentic 3' end without affecting the transcription
      efficiency. However, a 0.8 kbp sequence containing this motif could not produce a
      normal 3' end when joined to the 3' end of the nopaline synthase (NOS) gene
      instead of its 3' sequence. The results indicated that this conserved sequence is
      necessary but not sufficient for the 3'-end formation of H3 or NOS mRNA. Deletion
      of a 59 bp sequence, located 19 bp upstream from the AATGGAAATG sequence, also
      reduced the 3'-end formation efficiency by a factor of 10, compared with the
      efficiency in wild-type gene. We concluded that 3'-end formation of wheat histone
      H3 mRNA is regulated by multiple sequences including the AATGGAAATG motif.

PMID- 8152911
TI  - Detection of deletions in the mitochondrial genome of Caenorhabditis elegans.
AB  - We have examined an aging population of Caenorhabditis elegans via a PCR assay to
      determine if deletions in the mitochondrial genome occur in the nematode. We
      detected eight such deletions, identified the breakpoints of four of these, and
      discovered direct repeats of 4-8 base pairs at the site of all four deletions.
      Six of the eight repeats involved in the deletions are located in or immediately
      adjacent to tRNAs. Without a biochemical bias, the probability of direct repeats
      being present at all four breakpoints was 4 x 10(-6).

PMID- 8152912
TI  - Mutagenesis of the hairpin ribozyme.
AB  - Extensive in vitro mutagenesis studies have been performed on the hairpin
      ribozyme and substrate in an effort to refine the overall secondary structure of
      the molecule and provide further insight into what elements are essential for
      activity. A secondary structure consisting of four helices and five loop regions
      remains the basic model as originally proposed. Two helices, helix 1 and 2, form
      between the substrate and ribozyme while helices 3 and 4 are within the ribozyme
      itself. Our results suggest that helices 3 and 4 are smaller than previously
      proposed, consisting of four base pairs and three base pairs respectively. Helix
      4 can be extended without loss of activity and loop 3 at the closed end of the
      hairpin model can be varied in sequence with retention of activity. There is an
      unpaired nucleotide between helices 2 and 3 consisting of a single A base,
      suggesting the opportunity for flexibility within the tertiary structure at this
      point. Comparisons are made between the new data and previously published
      mutagenesis and phylogenetic data. Substrate targeting rules require base pairing
      between helices 1 and 2 with cleavage (*) occurring in a preferred
      5'(g/c/u)n*guc3' sequence of the substrate.

PMID- 8152913
TI  - Endogenous viral complexes with long RNA cosediment with the agent of Creutzfeldt
      Jakob disease.
AB  - A class of viruslike agents that induces Creutzfeldt-Jakob Disease (CJD) and
      scrapie remains undefined at the molecular level. Several investigators believe
      this infectious agent is constituted by a single host protein or 'prion', and
      have emphasized data that would seem to exclude the presence of any viral nucleic
      acids. However, more rigorous evaluations in scrapie have shown reasonably
      abundant nucleic acids. Additionally, in highly purified 120S CJD preparations
      that have been treated with nucleases, RNAs as long as 6,000 bases have been
      detected. Few nucleic acids have been characterized in either scrapie or CJD, but
      previous cloning experiments delineated relatively short LTR regions of the
      endogenous IAP retrovirus in 120S CJD preparations. We therefore used specific
      primers encompassing the entire IAP genome to test for the presence of long viral
      RNAs, and here show approximately 5,000 contiguous bases of the IAP RNA genome
      can be recovered from reasonable amounts of starting brain. The 3' env region of
      IAP is comparably truncated in CJD and normal preparations, and we find no
      evidence for IAP transduction of CJD-specific sequences. Because IAP cores can
      coencapsidate unrelated sequences, and are unusually resistant to physical and
      chemical treatments, it was relevant to find if cosedimenting cognate proteins of
      the IAP core, such as gag, could be detected. The predicted approximately 65 kd
      acidic gag protein, showing appropriate antigenic and nucleic acid binding
      features, was apparent in both one and 2-D Western blots. This data strongly
      indicates specific viral complexes cofractionate with the CJD agent.
      Interestingly, these nuclease resistant IAPs do not appear to be in
      morphologically recognizable 'R' particles. This cosedimenting viral assembly
      therefore provides a paradigm for non-particulate CJD complexes in infectious
      preparations. In developing strategies to identify a CJD specific sequence,
      cosedimenting IAPs can be used to assess the quality, length and recovery of RNAs
      extracted from highly resistant viral complexes.

PMID- 8152914
TI  - Identification and characterization of a novel repressor site in the human tumor
      necrosis factor alpha gene.
AB  - In human monocytic cell lines, tumor necrosis factor alpha (TNF alpha) expression
      is induced by phorbol myristate acetate (PMA). We have identified positive and
      negative cis-acting elements in the TNF alpha promoter by deletion analysis. Here
      we present the initial characterization of the repressor element. The repressor
      element was shown to function in either orientation and at various distances
      upstream from the positive element of the TNF alpha promoter. The TNF alpha
      repressor site (TRS) has been localized to a 25 bp region between base pairs -254
      and -230 in the promoter. This region contains a 10 bp sequence with homology to
      the binding site of the activator protein AP-2. Mutation of the 6 C's of this 10
      bp AP-2-like site abolish TRS repressor function. However, this AP-2-like site is
      not a binding site for AP-2 protein based on gel retardation analysis. In
      addition, a well-characterized AP-2-binding site placed upstream of the positive
      element of the TNF alpha gene did not cause repression. Therefore, this
      repression is very likely mediated by a novel protein(s) which interacts with the
      AP-2 consensus site in the TRS.

PMID- 8152915
TI  - Positive Factor 1 (PF1) from oat is an HMGY- and H1 histone-like protein that
      binds a functionally defined AT-rich DNA element in the oat phytochrome A gene
      (PHYA3) promoter.

PMID- 8152916
TI  - Production of high titre helper-free recombinant retroviral vectors by
      lipofection.

PMID- 8152917
TI  - A simple procedure for visualising protein-nucleic acid complexes by
      photochemical crosslinking.

PMID- 8152918
TI  - A novel assay for the DNA strand-transfer reaction of HIV-1 integrase.

PMID- 8152919
TI  - The effects of nucleoside analogs on telomerase and telomeres in Tetrahymena.
AB  - The ribonucleoprotein enzyme telomerase is a specialized type of cellular reverse
      transcriptase which synthesizes one strand of telomeric DNA, using as the
      template a sequence in the RNA moiety of telomerase. We analyzed the effects of
      various nucleoside analogs, known to be chain-terminating inhibitors of
      retroviral reverse transcriptases, on Tetrahymena thermophila telomerase activity
      in vitro. We also analyzed the effects of such analogs on telomere length and
      maintenance in vivo, and on vegetative growth and mating of Tetrahymena cells.
      Arabinofuranyl-guanosine triphosphate (Ara-GTP) and ddGTP both efficiently
      inhibited telomerase activity in vitro, while azidothymidine triphosphate (AZT
      TP), dideoxyinosine triphosphate (ddITP) or ddTTP were less efficient inhibitors.
      All of these nucleoside triphosphate analogs, however, produced analog-specific
      alterations of the normal banding patterns seen upon gel electrophoresis of the
      synthesis products of telomerase, suggesting that their chain terminating and/or
      competitive actions differ at different positions along the RNA template. The
      analogs AZT, 3'-deoxy-2',3'-didehydrothymidine (d4T) and Ara-G in nucleoside form
      caused consistent and rapid telomere shortening in vegetatively growing
      Tetrahymena. In contrast, ddG or ddI had no effect on telomere length or cell
      growth rates. AZT caused growth rates and viability to decrease in a fraction of
      cells, while Ara-G had no such effects even after several weeks in culture.
      Neither AZT, Ara-G, acycloguanosine (Acyclo-G), ddG nor ddI had any detectable
      effect on cell mating, as assayed by quantitation of the efficiency of formation
      of progeny from mated cells. However, AZT decreased the efficiency of programmed
      de novo telomere addition during macronuclear development in mating cells.

PMID- 8152921
TI  - Separate structural elements within internal transcribed spacer 1 of
      Saccharomyces cerevisiae precursor ribosomal RNA direct the formation of 17S and
      26S rRNA.
AB  - Structural features of Internal Transcribed Spacer 1 (ITS1) that direct its
      removal from Saccharomyces cerevisiae pre-rRNA during processing were identified
      by an initial phylogenetic approach followed by in vivo mutational analysis of
      specific structural elements. We found that S. cerevisiae ITS1 can functionally
      be replaced by the corresponding regions from the yeasts Torulaspora delbrueckii,
      Kluyveromyces lactis and Hansenula wingei, indicating that structural elements
      required in cis for processing are evolutionarily conserved. Despite large
      differences in size, all ITS1 regions conform to the secondary structure proposed
      by Yeh et al. [Biochemistry 29 (1990) 5911-5918], showing five domains (I-V; 5'-
      >3') of which three harbour an evolutionarily highly conserved element. Removal
      of most of domain II, including its highly conserved element, did not affect
      processing. In contrast, highly conserved nucleotides directly downstream of
      processing site A2 in domain III play a major role in production of 17S, but not
      26S rRNA. Domain IV and V are dispensable for 17S rRNA formation although an
      alternative, albeit inefficient, processing route to mature 17S rRNA may be
      mediated by a conserved region in domain IV. Each of these two domains is
      individually sufficient for efficient production of 26S rRNA, suggesting two
      independent processing pathways. We conclude that ITS1 is organized into two
      functionally and structurally distinct halves.

PMID- 8152920
TI  - Regulation of the Oct-4 gene by nuclear receptors.
AB  - To unravel the network of transcription factors established during development it
      is important to understand how genes specifically expressed during embryogenesis
      are regulated. Oct-4 is a transcription factor whose expression is associated
      with an undifferentiated cell phenotype in the early mouse embryo and is
      downregulated when such cells differentiate. An enhancer in the upstream region
      of Oct-4 has previously been reported as being sufficient to mediate the cell
      type specific expression and RA-dependent down-regulation in EC cells, although
      the enhancer contains no retinoic acid receptor (RAR) binding sites. Here we
      report the identification of promoter elements important for the regulation of
      the Oct-4 gene in EC cells. A region of the proximal Oct-4 promoter contains an
      overlapping set of regulatory elements including a high affinity binding site for
      Sp1 and three direct repeats of an AGGTCA-like sequence with either +1 or 0
      spacing. Binding and transient transfection assays reveal that Oct-4 is subject
      to negative regulation by different members of the steroid-thyroid hormone
      receptor superfamily. Specifically, important roles for ARP-1 and RAR in Oct-4
      expression are indicated.

PMID- 8152922
TI  - Fluorescence energy transfer as a probe for nucleic acid structures and
      sequences.
AB  - The primary or secondary structure of single-stranded nucleic acids has been
      investigated with fluorescent oligonucleotides, i.e., oligonucleotides covalently
      linked to a fluorescent dye. Five different chromophores were used: 2-methoxy-6
      chloro-9-amino-acridine, coumarin 500, fluorescein, rhodamine and ethidium. The
      chemical synthesis of derivatized oligonucleotides is described. Hybridization of
      two fluorescent oligonucleotides to adjacent nucleic acid sequences led to
      fluorescence excitation energy transfer between the donor and the acceptor dyes.
      This phenomenon was used to probe primary and secondary structures of DNA
      fragments and the orientation of oligodeoxynucleotides synthesized with the alpha
      anomers of nucleoside units. Fluorescence energy transfer can be used to reveal
      the formation of hairpin structures and the translocation of genes between two
      chromosomes.

PMID- 8152923
TI  - Divergence in codon usage of Lactobacillus species.
AB  - We have analyzed codon usage patterns of 70 sequenced genes from different
      Lactobacillus species. Codon usage in lactobacilli is highly biased. Both inter
      species and intra-species heterogeneity of codon usage bias was observed. Codon
      usage in L. acidophilus is similar to that in L. helveticus, but dissimilar to
      that in L. bulgaricus, L. casei, L. pentosus and L. plantarum. Codon usage in the
      latter three organisms is not significantly different, but is different from that
      in L. bulgaricus. Inter-species differences in codon usage can, at least in part,
      be explained by differences in mutational drift. L. bulgaricus shows GC drift,
      whereas all other species show AT drift. L. acidophilus and L. helveticus rarely
      use NNG in family-box (a set of synonymous) codons, in contrast to all other
      species. This result may be explained by assuming that L. acidophilus and L.
      helveticus, but not other species examined, use a single tRNA species for
      translation of family-box codons. Differences in expression level of genes are
      positively correlated with codon usage bias. Highly expressed genes show highly
      biased codon usage, whereas weakly expressed genes show much less biased codon
      usage. Codon usage patterns at the 5'-end of Lactobacillus genes is not
      significantly different from that of entire genes. The GC content of codons 2-6
      is significantly reduced compared with that of the remainder of the gene. The
      possible implications of a reduced GC content for the control of translation
      efficiency are discussed.

PMID- 8152924
TI  - Octamer displacement and redistribution in transcription of single nucleosomes.
AB  - Single nucleosomes were assembled on a 357bp DNA fragment containing a 5S RNA
      gene from sea urchin and a promoter for SP6 RNA polymerase, and were fractionated
      as a function of their positions by gel electrophoresis. Transcribed nucleosome
      positions were detected by observing band disappearance in gels, which in turn
      provided evidence for the displacement of the histone octamer upon transcription.
      Differential band disappearance showed that nucleosomes closer to the promoter
      were harder to transcribe, and transcription was blocked when the nucleosome
      proximal boundary was at the start site. Nucleosomes located at discrete
      positions were also eluted from the gel bands and transcribed. In this case, new
      bands appeared as a consequence of octamer redistribution. Such redistribution
      occurred over all untranscribed positions, as well as over transcribed positions
      close enough to the promoter. Similar conclusions were derived from another
      previously investigated fragment containing a Xenopus 5S RNA gene.

PMID- 8152925
TI  - Evidence for a protein domain superfamily shared by the cyclins, TFIIB and
      RB/p107.
AB  - Cyclins, TFIIB and RB play major roles in cell cycle and/or gene regulation.
      Earlier work has suggested common ancestry for the TFIIB repeats and RB pocket B
      which share 20% sequence identity. We now report that database searches with
      profiles based on a multiple alignment of cyclin core regions (the 'cyclin box')
      detect the TFIIB repeats with equivalent scores to divergent cyclins. Several
      features of the sequences support the notion of common ancestry: e.g. cyclins
      A/B, C and D share approximately 20-30% identity but each have approximately 15
      20% identity with vertebrate TFIIB, showing that conserved cyclin features
      underlie the match. These results suggest the presence of a domain superfamily,
      which we term the TR domain, in nuclear regulatory proteins belonging to the
      TFIIB, cyclin and RB families, that has been duplicated many times during
      eukaryotic evolution. The TR domain appears to function in protein-protein
      interactions.

PMID- 8152926
TI  - Are there two DNA methyltransferase gene families in plant cells? A new potential
      methyltransferase gene isolated from an Arabidopsis thaliana genomic library.
AB  - Using the 1kb 3' terminal DNA fragment of the mouse methyltransferase cDNA as a
      probe and low stringent hybridisation conditions, a new potential
      methyltransferase (MTase) gene family was isolated from an Arabidopsis thaliana
      genomic DNA library. One clone (MTase-11), which gave the strongest signal at the
      Northern blot, was entirely sequenced (11483 bp) and further characterised. Under
      consideration of the likely open reading frames and our preliminary cDNA
      experiments we propose that the clone 11 gene encodes for an approximately 90 kD
      protein. As deduced form the DNA sequence this protein contains all conserved
      sequence motifs specific for the 5m cytosine MTases. MTase-11 gene expression was
      demonstrable in callus and during germination but not in one month old plants or
      in leaves.

PMID- 8152927
TI  - Tissue specific expression and cDNA structure of a human transcript encoding a
      nucleic acid binding [oligo(dC)] protein related to the pre-mRNA binding protein
      K.
AB  - In human cells at least 20 different proteins or groups of proteins have been
      identified that are associated with hnRNAs. These proteins (designated A1-U) are
      highly abundant in the nucleus. In this study, we present the sequence of a novel
      cDNA clone, sub2.3, isolated from a human lymphocyte cDNA library. The predicted
      amino acid sequence shows homology to repeated domains in the human hnRNA binding
      protein K (hnRNP K), which are believed to be of functional importance. hnRNP K
      is among the major oligo(rC/dC) binding proteins in vertebrate cells and we show
      here that the protein product of sub2.3 also binds to oligo(dC). This is shown by
      a novel approach where we demonstrated specific binding of in vitro translated
      sub2.3 protein to biotinylated oligo(dC) which was immobilized on magnetic
      streptavidin-coated Dynabeads. Moreover we found that the sub2.3 transcript is
      expressed in a tissue dependent manner with the highest expression observed in
      several lymphoid tissues and skeletal muscle. The gene was also abundantly
      expressed in several lymphoid cell lines and the hepatoma cell line HepG2 while a
      low expression was observed in the HL60 myeloid cell line and in the HeLa
      cervical carcinoma cell line. In conclusion, this study presents the cDNA
      sequence of a novel transcript which shows tissue specific expression and encodes
      a protein with oligo(dC) binding specificity in vitro.

PMID- 8152928
TI  - Recognition sequence of a highly conserved DNA binding protein RBP-J kappa.
AB  - DNA binding specificity of the RBP-J kappa protein was extensively examined. The
      mouse RBP-J kappa protein was originally isolated as a nuclear protein binding to
      the J kappa type V(D)J recombination signal sequence which consisted of the
      conserved heptamer (CACTGTG) and nonamer (GGTTTTTGT) sequences separated by a 23
      base pair spacer. Electrophoretic mobility shift assay using DNA probes with
      mutations in various parts of the J kappa recombination signal sequence showed
      that the RBP-J kappa protein recognized the sequence outside the recombination
      signal in addition to the heptamer but did not recognize the nonamer sequence and
      the spacer length at all. Database search identified the best naturally occurring
      binding motif (CACTGTGGGAACGG) for the RBP-J kappa protein in the promoter region
      of the m8 gene in the Enhancer of split gene cluster of Drosophila. The binding
      assay with a series of m8 motif mutants indicated that the protein recognized
      mostly the GTGGGAA sequence and also interacted weakly with ACT and CG sequences
      flanking this hepta-nucleotide. Oligonucleotides binding to the RBP-J kappa
      protein were enriched from a pool of synthetic oligonucleotides containing 20
      base random sequences by the repeated electrophoretic mobility shift assay. The
      enriched oligomer shared a common sequence of CGTGGGAA. All these data indicate
      that the RBP-J kappa protein recognizes a unique core sequence of CGTGGGAA and
      does not bind to the V(D)J recombination signal without the flanking sequence.

PMID- 8152929
TI  - The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA.
AB  - The modified base, 5-methylcytosine, constitutes approximately 1% of human DNA,
      but sites containing 5-methylcytosine account for at least 30% of all germline
      and somatic point mutations. A genetic assay with a sensitivity of 1 in 10(7),
      based on reversion to neomycin resistance of a mutant pSV2-neo plasmid, was
      utilized to determine and compare the deamination rates of 5-methylcytosine and
      cytosine in double-stranded DNA for the first time. The rate constants for
      spontaneous hydrolytic deamination of 5-methylcytosine and cytosine in double
      stranded DNA at 37 degrees C were 5.8 x 10(-13) s-1 and 2.6 x 10(-13) s-1,
      respectively. These rates are more than sufficient to explain the observed
      frequency of mutation at sites containing 5-methylcytosine and emphasize the
      importance of hydrolytic deamination as a major source of human mutations.

PMID- 8152930
TI  - Biological availability and nuclease resistance extend the in vitro activity of a
      phosphorothioate-3'hydroxypropylamine oligonucleotide.
AB  - Augmented biological activity in vitro has been demonstrated in oligonucleotides
      (oligos) modified to provide nuclease resistance, to enhance cellular uptake or
      to increase target affinity. How chemical modification affects the duration of
      effect of an oligo with potent activity has not been investigated directly. We
      postulated that modification with internucleotide phosphorothioates and 3'
      alkylamine provided additional nuclease protection which could significantly
      extend the biological activity of a 26 mer, (T2). We showed this analog, sT2a,
      could maximally inhibit interferon gamma-induced HLA-DR mRNA synthesis and
      surface expression in both HeLa and retinal pigmented epithelial cells and could
      continue to be effective, in the absence of oligo, 15 days following initial
      oligo treatment; an effect not observed with its 3'amine counterpart, T2a. In
      vitro stability studies confirmed that sT2a conferred the greatest stability to
      nucleases and that cellular accumulation of 32P-sT2a in both cell types was also
      greater than other T2 oligos. Using confocal microscopy, we revealed that the
      intracellular distribution of sT2a favored greater nuclear accumulation and
      release of oligo from cytoplasmic vesicles; a pattern not observed with T2a.
      These results suggest that phosphorothioate-3'amine modification could increase
      the duration of effect of T2 oligo by altering nuclease resistance as well as
      intracellular accumulation and distribution; factors known to affect biological
      availability.

PMID- 8152931
TI  - Construction of a normalized cDNA library by introduction of a semi-solid mRNA
      cDNA hybridization system.
AB  - We report a novel procedure to construct a normalized (equalized) cDNA library.
      By introduction of the highly efficient self-hybridization system between a whole
      mRNA population and their corresponding cDNA immobilized on latex beads, which
      involves relatively simple manipulations, we were able to generate an mRNA
      population in which the copy number of abundant species was reduced while that of
      rare species was enriched. In a typical experiment, after several cycles of self
      hybridization on the beads, the ratio of the most to the least abundant marker
      mRNA species dropped by a factor of 300 (from 10,000 to 30) while the complexity
      and length of mRNAs in the population remained unchanged. The procedure should
      provide a potent tool for the expression cloning of cDNA and also facilitate the
      construction of whole cDNA catalogs from specific tissues (or cell types) from
      higher organisms.

PMID- 8152933
TI  - Development of the Breast-Feeding Attrition Prediction Tool.
AB  - The psychometric properties of the revised Breast-Feeding Attrition Prediction
      Tool, based on the Theory of Planned Behavior, were examined in this study. The
      sample consisted of 201 postpartum women who planned to breast-feed at least 8
      weeks. Four scales identified by factor analysis measured the three TPB
      constructs. All scales showed moderate internal consistency (alphas .79 to .85).
      Two scales distinguished between women with and without prior breast-feeding
      experience (p < .05). Three scales were significantly related to breast-feeding
      attrition at 8 weeks. Women who weaned prematurely received less breast-feeding
      support from their social and professional network, believed breast-feeding was
      difficult, and saw more advantages to formula feeding than to breast-feeding. A
      discriminant analysis of the scales correctly identified 73% of the women who
      weaned prematurely.

PMID- 8152932
TI  - Involvement of SRE element of Ty1 transposon in TEC1-dependent transcriptional
      activation.
AB  - Some Ty1 transposable element insertion mutations of Saccharomyces cerevisiae
      activate transcription of adjacent genes in a cell-type dependent manner. This
      activation requires at least STE12 and TEC1 gene products. The binding site for
      the STE12 protein is located in the sterile responsive element (SRE), which is
      just downstream the 5' LTR of Ty1 and contains one copy of the pheromone response
      element (PRE). This report defines the sequences in Ty1 required for TEC1
      dependent activation using a TDH3::lacZ reporter gene in which the UAS was
      replaced by different portions of a Ty1 or Ty2 element. The Ty1 SRE seems to be
      sufficient to ensure the TEC1 and STE12-mediated activation whereas Ty2 SRE can
      activate the expression of the adjacent genes in the absence of both proteins.
      Adjacent to the PRE element, there is a region (PAE) with extensive sequence
      divergence in Ty1 and Ty2 SREs. Swapping experiments between Ty1 and Ty2
      sequences show that Ty1 PAE is required for the activation of adjacent gene
      expression in a TEC1 and STE12-dependent manner. The use of a LexA::TEC1
      construct indicates that the chimeric protein has no activation ability
      suggesting that TEC1 could act in conjunction with another factor.

PMID- 8152934
TI  - Maternal identity and role attainment: long-term relations to children's
      development.
AB  - Mother-infant pairs were assessed during postpartum for maternal role and
      identity and a variety of infant and sociodemographic characteristics. When
      children were school age (8 to 10 years), 77 of the original 124 mothers returned
      a mail survey that assessed children's social competence and behavioral problems.
      After controlling for socioeconomic status, neither perceived nor demonstrated
      role attainment predicted child outcomes. Only a subset of the maternal identity
      indicators predicted children's social competence and behavior problems at 9
      years, and these relationships were few and modest in magnitude. Overall, little
      support was found for the long-term predictive power of maternal role indicators
      measured during postpartum.

PMID- 8152935
TI  - Effects of clarification of support expectations in prenatal couples.
AB  - The purpose of this study was to test a theoretical model of confirmation of
      expectations for mutual support after childbirth and to evaluate an intervention
      given in prenatal classes during which prospective parents clarified their
      expectations. Results provided support for the proposed model in that parents
      with greater confirmation of expectations were found to have more positive
      relationship satisfaction, emotional affect, and parenting attitudes. Differences
      in men and women emerged that demonstrated that confirmation of support
      expectations was more important to women, while the level of support actually
      received was more important to men. The prenatal class intervention did not
      significantly affect parent outcomes.

PMID- 8152936
TI  - Determination of reading comprehension level for effective patient health
      education materials.

PMID- 8152937
TI  - Implementation of work sampling methodology.

PMID- 8152938
TI  - Using the SAS system to estimate sample size and power for comparing two binomial
      proportions.

PMID- 8152939
TI  - The ghost of Tuskegee.

PMID- 8152940
TI  - Attachment and quality of life in older, community-residing men.
AB  - The purpose of this study was to determine the extent to which demographic
      variables and attachment predicted quality of life in community-dwelling older
      men. The subjects were 100 men aged 58 to 84 (M = 68.4). Hierarchical regression
      revealed that two demographic variables, plus the attachment variable, accounted
      for 30% of the variance in predicting quality of life. Having no limiting health
      condition accounted for 17% of the variance, while education accounted for an
      additional 5% of the variance. The attachment total score accounted for an
      additional 8% of the variance in predicting quality of life.

PMID- 8152941
TI  - Contextual factors associated with disturbing behaviors in institutionalized
      elders.
AB  - Data from a longitudinal clinical trial funded by the National Institute of
      Aging, testing the effects of staff education and consultation on restraint
      reduction in nursing homes, were used to examine disturbing behaviors in
      institutionalized elders and to identify related environmental and personal
      characteristics. Subjects were 586 residents from three well-matched nursing
      homes. Kayser-Jone's (1989) model on environment and quality of life in long-term
      care institutions served as the organizing framework. Data on disturbing
      behaviors from the Psychogeriatric Dependency Rating Scale were factor analyzed.
      Three factors, Agitated Psychomotor Behaviors, Aggressive Interpersonal
      Communication, and Expressive Difficulty, emerged from the principal factor
      analysis and accounted for 35% of the variance. The Kayser-Jones model partially
      explained Agitated Psychomotor Behavior (R2 = .22). A model comparison approach
      indicated that the addition of an organizational variable, staff mix,
      significantly increased the amount of variance explained over and above that
      contributed by the personal variables.

PMID- 8152942
TI  - Predictors of paternal role competence by risk status.
AB  - One hundred seventeen men whose partners had experienced a low-risk pregnancy
      (LRM) and 61 men whose partners had been hospitalized during pregnancy for an
      obstetrical risk (HRM) were studied to determine whether they differed in
      paternal role competence from the time of their partners' early postpartal
      hospitalization to 1, 4, and 8 months after birth. No differences were found
      between LRM and HRM in paternal role competence, and their trajectory of paternal
      competence did not differ. During the 1-month and 8-month postpartal period,
      paternal competence increased from 76.07 to 77.14 for HRM and from 77.21 to 78.29
      for LRM. From 15% to 34% of the variance in paternal competence was explained
      among HRM, and from 41% to 44% was explained among LRM. Anxiety was the major
      predictor of paternal role competence for HRM, and sense of mastery and
      depression were major predictors for LRM.

PMID- 8152943
TI  - Health-promoting behaviors of African American women.
AB  - Limited information exists concerning health behaviors of African American women.
      The purposes of this study were to describe health-promoting lifestyle behaviors
      among a sample of 187 African American women and to compare findings to other
      published reports on the Health-Promoting Lifestyle Profile (HPLP) instrument.
      Subscales with the highest means in this study were interpersonal support and
      self-actualization. However, when compared to reports of HPLP scores for other
      groups, total HPLP and subscale scores of women in this study were generally
      lower. Readability and applicability of the HPLP instrument may affect its
      validity and reliability in a diverse sample.

PMID- 8152944
TI  - Physiologic status, coping, and hardiness as predictors of outcomes in chronic
      obstructive pulmonary disease.
AB  - The purpose of this study was to examine the relationship of physiologic status,
      coping, and hardiness to exercise ability and functional status in 96 adult
      patients with chronic obstructive pulmonary disease (COPD). Exercise ability was
      measured by the distance walked in 12 minutes (12MD) and functional status by the
      Pulmonary Functional Status Scale (PFSS). The mean FEV1 and FVC were 1.61 +/- .81
      and 3.08 +/- .95 L, respectively. The commitment (r = -.18) and challenge (r = 
      .21) components of hardiness were significantly correlated with the 12MD. The
      commitment component of hardiness was significantly correlated with functional
      status (r = -.17). Control was not a significant variable. Physiological status,
      problem-solving coping, and challenge were the best predictors of exercise
      ability (R2 = .26). Physiological status and commitment were the best predictors
      of functional status (R2 = .149).

PMID- 8152945
TI  - The meaning of stressful life experiences in nine- to eleven-year-old children: a
      phenomenological study.
AB  - The meaning of stressful life experiences was explored in 14 children, 9 to 11
      years of age, using the phenomenological method. Data from audiotaped interviews
      were analyzed using the methodological approach of Giorgi. The children
      identified 17 categories of situations concentrated within three principal
      dimensions: feelings of loss, feelings of threat to self, and feelings of being
      hassled. The participants indicated that experiences related to loss, although
      infrequent, were of great consequence in their lives. The interviews demonstrated
      the frequency of situations that evoke feelings of threat to self or create
      hassles in children's lives.

PMID- 8152947
TI  - Professional development. Breaking bad news: knowledge for practice (continuing
      education credit).

PMID- 8152946
TI  - Teaching and learning in practice. 6. Communication and effective learning. (iv).
      Communication and the learning environment (continuing education credit).

PMID- 8152948
TI  - An act of will.

PMID- 8152950
TI  - Revolutionary project.

PMID- 8152949
TI  - Smoke alarm.

PMID- 8152951
TI  - Women's health. Global awareness.

PMID- 8152952
TI  - Women's health. An unequal struggle.

PMID- 8152953
TI  - Women's health. Coping strategy.

PMID- 8152954
TI  - Staff support. Downsizing distress.

PMID- 8152955
TI  - Systems of life. Taste. 1.

PMID- 8152956
TI  - A wide body.

PMID- 8152957
TI  - In the best place?

PMID- 8152958
TI  - The emotional void.

PMID- 8152959
TI  - Continence. Youthful issues.

PMID- 8152960
TI  - Continence. Read all about it.

PMID- 8152961
TI  - Continence. Muscle control.

PMID- 8152962
TI  - Anger mounts over HIV disclosures.

PMID- 8152963
TI  - Teaching and learning in practice. 6. Communication and effective learning.
      (iii). Negotiated study and learning contracts (continuing education credit).

PMID- 8152964
TI  - Homosexual men's views on visiting GPs.

PMID- 8152966
TI  - Delivery dilemma.

PMID- 8152967
TI  - Career changes. A bitter blow.

PMID- 8152965
TI  - The loss adjusters.

PMID- 8152968
TI  - Career changes. Go for it.

PMID- 8152969
TI  - Making sense of the effects of smoking.

PMID- 8152970
TI  - Women's health. Please tell mother.

PMID- 8152971
TI  - Complex therapy.

PMID- 8152973
TI  - Learning together.

PMID- 8152972
TI  - Stately union.

PMID- 8152974
TI  - Attitude problems.

PMID- 8152975
TI  - Complementary medicine. Using aromatherapy in childbirth.

PMID- 8152976
TI  - Concern over HIV disclosure rules.

PMID- 8152977
TI  - Complementary medicine. Nature's pharmacy.

PMID- 8152978
TI  - Ageing matters. Advocates of independence.

PMID- 8152979
TI  - Ageing matters. Supporting role.

PMID- 8152980
TI  - Restoration deterioration related to later failure.
AB  - The purpose of this study was to determine the relationship between the
      deterioration and the later failure of a very large number of amalgams and
      anterior resin composites examined over periods of up to 16 years. Assessments
      were made of the deterioration of various clinical factors or characteristics of
      the restorative materials that were thought to predict later failures. True
      failures, which were directly related to the restorative materials, accounted for
      7.5% of the amalgam and 30.4% of the composite restorations. For the amalgams,
      there was a significant association found between the failures and surface
      tarnishing. Marginal fracture and marginal staining were not associated
      significantly with any of the three different failure modes. For the composites
      there were significant associations found between the failures and surface
      roughness, marginal fracture, and color mismatch. Surface staining and marginal
      staining were not associated significantly with any of the three different
      failure modes. Many restorations assessed as being unsatisfactory continued to
      function for a further 2.5 to 3.5 years on average before being replaced, often
      for unrelated reasons. There is a need to define unsatisfactory restorations more
      clearly in terms of actual adverse effects on dental health, rather than merely
      in terms of restoration deterioration.

PMID- 8152981
TI  - Adhesive interface between resin and etched dentin of cervical erosion/abrasion
      lesions.
AB  - The interfacial structure between an adhesive composite resin and the dentinal
      walls of cervical erosion/abrasion lesions etched with 37% phosphoric acid gel
      for 60 seconds was investigated. Almost all dentinal tubules were occluded with
      rod-like structural depositions that remained undissolved even after acid
      conditioning. The hybrid layer between the adhesive resin and surface
      demineralized dentin was found to be 0.3 to 3 microns, much thinner than that
      routinely found in either normal dentin or cariously affected dentin. The hybrid
      layer was thinnest at the occlusal walls of the cavity where the dentinal tubules
      run parallel to the cavity surface. The bond strength of adhesive resin to these
      areas may differ from that to intact normal dentin.

PMID- 8152982
TI  - Composite resin bond strength after enamel bleaching.
AB  - This study evaluated the effect of enamel bleaching with a commercial product on
      the sheer bond strength of a composite resin. A total of 45 human extracted
      permanent molars were used. A flat enamel surface was obtained with 600-grit SiC
      paper. The teeth were then randomly distributed into three groups of 15 teeth
      each: Group 1: Enamel etching with 37% phosphoric acid gel (Coe) for 60 seconds,
      placement of an unfilled resin (Coe) thinly applied with a brush and a composite
      resin (Occlusin); Group 2: Enamel bleaching (Rembrandt Lighten Bleaching Gel, Den
      Mat) for one hour, etching for 60 seconds and placement of unfilled and composite
      resins. Group 3: Enamel bleaching for 24 hours, etching for 60 seconds, and
      placement of unfilled and composite resins. A nylon ring over the etched enamel
      retained the composite resin. The teeth were thermocycled (X100) and sheared with
      a knife-edged blade in an Instron machine running at a cross-head speed of 1
      mm/min. The results in MPa were: Group 1: 12.86 +/- 4.83, Group 2: 12.33 +/-
      2.95, and Group 3: 7.67 +/- 1.98. An ANOVA revealed that Groups 1 and 2 were
      significantly different from Group 3 (P < 0.001). Fracture within the enamel
      occurred in 53% in Group 1, 33% in Group 2, and 0% in Group 3. The study reveals
      that the shear bond strength of composite resins is significantly reduced after
      enamel bleaching for 24 hours.

PMID- 8152983
TI  - A clinical trial to evaluate the retention of a silver cermet-ionomer cement used
      as a fissure sealant.
AB  - A randomized clinical trial was under-taken to compare the retention of a silver
      cermet-ionomer cement, Ketac Silver, with a conventional, autopolymerizing BIS
      GMA resin sealant, Delton, using matched pairs of fissure sites within each
      subject's mouth. One hundred twenty matched contralateral pairs of fissure sites
      in first and second permanent molars of 53 school children were sealed with the
      two materials. The choice of site and material was selected at random. The ages
      of the children ranged from five to 16 years; first permanent molars were sealed
      in the five- to 10-year age group, and second permanent molars in the 11- to 16
      year age group. Sealants were assessed as present, partly present, or absent at
      6, 12, and 24 months. The number of pairs of sites available for reassessment
      declined from 102 at six months to 59 at 24 months as patients were lost to the
      study. Retention rates were higher for the Ketac Silver sealants at all three
      inspection intervals (P < 0.01): 93% compared with 74% at six months, 81%
      compared with 65% at 12 months, and 83% compared with 58% at 24 months. When
      analyzed according to age range, the difference between the retention rates was
      statistically significant in the five- to 10-year-olds but not significant in the
      11- to 16-year-olds. The conclusion reached in this study was that cermet cement
      was better retained than conventional resin sealants in younger children.

PMID- 8152984
TI  - Effects of design features and restorative techniques on marginal leakage of MO
      composites: an in vitro study.
AB  - Effects of clinical practices on marginal leakage of MO composite restorations
      were studied in vitro. Three design scenarios and three restorative techniques
      were studied. A total of 45 premolars were used, providing five specimens for
      each of the nine design-technique permutations. The extent of marginal leakage
      was measured under magnification, after soaking the samples in a dye and then
      sectioning each sample mesiodistally. No significant differences were found
      between the permutation groups, although some clinical practices resulted in a
      lowered mean amount of marginal leakage.

PMID- 8152985
TI  - Fracture strength and fracture patterns of maxillary premolars with approximal
      slot cavities.
AB  - The fracture strength and fracture patterns of maxillary premolar teeth prepared
      with two different cavity designs and tested with and without amalgam
      restorations were determined. No significant difference in the fracture strength
      of intact premolars and premolars prepared with conventional MOD cavities or slot
      MO/DO cavities was found whether or not the teeth were restored with amalgam.
      However, fracture pattern analysis revealed significant differences among the
      groups of teeth. Premolars with MO/DO slot cavities or slot amalgam restorations
      exhibited minimal fractures that involved enamel only in the majority of the
      cases. This behavior was similar to what was observed with intact premolars. In
      contrast, premolars with conventional MOD cavities or MOD amalgam restorations
      exhibited severe fractures that involved enamel, dentin, and the root in the
      majority of the cases. These severe fractures were statistically significantly
      different from those of premolars with slot cavities or slot restorations as well
      as from those of intact premolars. It is concluded that when maxillary premolars
      require restoration of carious lesions on both approximal sides without occlusal
      involvement, MO/DO slot amalgam restorations will be expected to result in teeth
      that are unlikely to undergo severe cuspal fracture compared to conventional MOD
      amalgam restorations.

PMID- 8152986
TI  - Microleakage of a dental amalgam alloy bonding agent.
AB  - Amalgambond (a 4-META derivative resin bond agent) was evaluated for its
      effectiveness in reducing microleakage compared to copal varnish and no lining
      agent in class 5 amalgam preparations restored with either an admix alloy
      (Dispersalloy) or a spherical alloy (Tytin). Teeth were thermocycled between 5
      and 55 degrees C with two 4-META/amalgam groups additionally aged in 37 degrees C
      water for 30 days prior to thermocycling. Nonaged, 4-META/amalgam restorations
      showed significantly less microleakage (P < 0.05) at enamel and dentin margins
      compared to copal varnish or nonlined restorations. Within the 4-META groups, the
      4-META/Dispersalloy restorations had significantly less microleakage than the 4
      META/Tytin restorations at enamel margins. Microleakage in the aged 4
      META/amalgam restorations was significantly greater at both the enamel and dentin
      margins than in the analogous nonaged groups. SEM evaluation of the 4-META lined
      restorations found internal cavity surfaces of the preparations to be sealed by
      the resin liner with separations and apparent microleakage occurring at the 4
      META/amalgam interface.

PMID- 8152987
TI  - Review of periodontal considerations and surgical retraction techniques for
      operative dentistry.
AB  - Gingival margins of restorations should generally be placed supragingivally or at
      the gingival crest; however, some valid parameters exist for the extension of
      margins into the gingival crevice. The successful restoration of teeth in
      subgingival locations requires familiarity with periodontal anatomy. This paper
      reviews periodontal considerations, then presents several surgical techniques
      that facilitate access and improve the periodontal prognosis of teeth that have
      been compromised through fracture, caries, prior restorative treatment, or habit.

PMID- 8152988
TI  - Repair of an aged, contaminated indirect composite resin with a direct, visible
      light-cured composite resin.
AB  - This study investigated the interfacial shear bond strength of a contaminated,
      aged, heat- and pressure-processed, indirect composite resin (Concept) repaired
      with a direct, visible-light-cured composite resin (Heliomolar). Concept samples
      were aged by thermocycling and contaminated in tobacco juice. The bonding
      surfaces were prepared by sanding with 500-grit sandpaper or air abrading with 50
      micron aluminum oxide. Prepared Concept surfaces received one or more of the
      following intermediary resin treatments before the addition of Heliomolar:
      Heliobond, Special Bond 2, All-Bond system, All-Bond bonding agent, or no bonding
      agent, and they were immediately thermocycled. Air abrasion produced
      significantly higher bond strengths than sanding for all intermediary resin
      surface treatments. The All-Bond-treated Concept surfaces showed the highest
      interfacial bond strengths within the air abraded and sanded groups. Visual and
      SEM examination of fractured repair surfaces indicated adhesive failure within
      all treatment groups.

PMID- 8152989
TI  - The efficacy of dental sealants for an adult population.
AB  - A 1-year pilot study was conducted to determine the retentive capacities of
      dental sealants on adult teeth. It proposed to utilize the knowledge and
      experience gained in sealant application, as a means of attacking the problem of
      the increase in restored teeth at risk in the aging population. Eighty patients
      aged 30-50 had Delton tinted sealant applied on one to four contralateral
      nonhomologous, first or second, acceptable molar pairs. Fifty-five patients
      completed the evaluation at 1 year, with a 68% retention for 250 teeth: teeth
      listed as sound, 94.1%; IC and IC-amalgam, 93.7%, and amalgam, 44.9%.

PMID- 8152990
TI  - Reasons for placement and replacement of dental restorations in the United States
      Navy Dental Corps.
AB  - This study investigated the reasons for placement and replacement of dental
      restorations in the United States Navy Dental Corps. The relationship between
      restoration longevity and the reasons for replacement of restorations was also
      studied. Data on newly placed dental restorations were collected from restorative
      dentists working at 11 Naval Dental Clinics located throughout the United States.
      Participating dentists at each clinic were asked to collect data for all
      restorations they placed during a two-week period. Data on 4633 restorations were
      collected from 88 dentists. The most common reasons for placement of restorations
      varied by age category. Primary caries was the most common reason for patients 18
      34 years of age, while noncarious reasons for placement were most common for
      patients 35 years of age and older. The most common reason for replacement of
      restorations was secondary caries. For all replacement reasons amalgam
      restorations had greater longevity than composite resin restorations.

PMID- 8152991
TI  - Effect of grooves on resistance/retention form of Class 2 approximal slot amalgam
      restorations.
AB  - This study evaluated in vitro the effectiveness of resistance/retention grooves
      in box-only (approximal slot) class 2 preparations. Forty-eight sound, caries
      free maxillary premolars were distributed equally into four groups of 12 teeth
      based on faciolingual dimensions. Teeth were mounted vertically, and class 2
      mesio-occlusal slot preparations were cut in each tooth. Resistance/retention
      grooves were placed in three of the four groups with a #1/4 round bur to a depth
      of 0.3-0.5 mm. Teeth were restored with amalgam and positioned 13.5 degrees from
      vertical; an area was flattened on each amalgam marginal ridge, and the flattened
      areas were loaded to failure using an Instron with a rectangular flat-ended rod
      at a cross-head speed of 1 mm/min. Mean load (SD) to failure of the group using
      "conventional" grooves extending in dentin from the gingival floor occlusally to
      near the occlusal DEJ was 196N (46N). For long grooves extending from the
      gingival floor to the occlusal surface, the mean failure load was 169N (58N).
      Slot restorations with short resistance/retention grooves or points (0.5-1.0 mm)
      just gingival to the occlusal DEJ had a mean failure load of 132N (44N). Slot
      restorations with no grooves had a mean failure load of 69N (46N). ANOVA and
      Student-Newman-Keuls tests were used for analysis. The no-groove group provided
      significantly less (P < 0.01) resistance than any group with grooves. Approximal
      slot restorations with "conventional" grooves were significantly more resistant
      (P < 0.01) than those with short grooves but were not significantly more
      resistant than those with long grooves.

PMID- 8152992
TI  - Rube lives?

PMID- 8152993
TI  - Photoelastic stress analysis of self-threading pins.
AB  - In this laboratory study six self-threading retention pins were evaluated using
      the two-dimensional photoelastic technique. The experimental samples consisted of
      60 blocks of PSM-1 photoelastic material measuring 1" by 1" by 1/4". The samples
      were divided into six groups of 10 blocks each, with each group representing one
      of the pins used in the study. Pins were inserted and cores of amalgam and
      composite were fabricated over the pins. The samples were observed in the
      polariscope and photographed after pin insertion and after loading the cores with
      a constant, compressive force of 20 pounds. Using magnification, fringe orders
      were counted and rounded to the highest 0.5 fringe order. Each sample was
      evaluated for apical and shoulder stress. All statistical analyses were done
      using ANOVA at the P = 0.05 significance level. It was concluded from this study
      that the insertion of self-threading retention pins results in stress at the
      apical and shoulder areas of the pin. Pin design features, such as shoulder
      stops, significantly affect the magnitude and location of stress. There were no
      significant differences in either the apical or shoulder stresses induced when
      cores were made of either amalgam or composite resin.

PMID- 8152994
TI  - Perceived trends in operative dentistry skills: a 10-year comparison.
AB  - In this study a random sample of 357 members of dental examiner boards in the
      United States was surveyed to determine the perceptions of candidate ability on
      examinations for dental licensure. A response rate of 82% was achieved. Data from
      this survey were compared to a similar survey conducted 10 years ago. Analysis
      and comparison of these two surveys indicate that candidate ability in operative
      dentistry has continued to decline as perceived by dental examiners in the United
      States over the past decade.

PMID- 8152995
TI  - The effect of cavity wall taper on fracture resistance of teeth restored with
      resin composite inlays.
AB  - The effect of a range of cavity wall tapers on fracture resistance of teeth
      restored with an indirect composite restoration (ICR) system has been
      investigated, using two methods of application of the fracturing force. The
      fracture load data are similar in both cases, and in neither case does ANOVA
      suggest a statistically significant difference in performance with cavity taper.
      However, the mean values are lower for the 6 degrees taper specimens, and linear
      regression suggests a significant decrease, which is confirmed by the mode data
      for the bar loading condition, which indicates a greater incidence of severe
      fractures for the 6 degrees taper. Since technical difficulties were encountered
      in the construction of inlays for the 2 degrees taper preparations, the most
      appropriate taper of the range assessed would appear to be 4 degrees, at least
      when considered with regard to fracture resistance.

PMID- 8152996
TI  - Microleakage of Class 5 composite resin restorations: a comparison between in
      vivo and in vitro.
AB  - The purpose of this study was to determine if a difference exists in microleakage
      between in vivo and in vitro class 5 composite resin restorations using two
      variations of a bonding resin (Universal Bond 2 and Universal Bond 3). Class 5
      cavities were prepared in 24 matched pairs of teeth on the buccal and lingual
      surfaces. One tooth of each pair was prepared and restored in vivo and the other
      in vitro. After preparation and enamel etching, Universal Bond 2 was randomly
      applied to one surface of each tooth in the pair and Universal Bond 3 to the
      other surface. Composite resin (Prisma AP.H) was placed in each preparation,
      light cured, and finished using a standard technique. The in vivo samples were
      extracted approximately 6 weeks after placement of the restorations. The in vitro
      samples were thermocycled for 540 cycles (5 to 55 degrees C/1-minute dwell time).
      All teeth were stained with silver nitrate and longitudinally divided. The teeth
      were scored on a ranking system of 0 being no leakage to 4 being leakage to the
      pulpal wall of the preparation. A Wilcoxon matched pairs signed rank test was
      performed on the data (P < or = 0.05). There were no statistically significant
      differences in microleakage between restorations using Universal Bond 2 and
      Universal Bond 3. There were statistically significant differences when comparing
      the in vivo and in vitro restorations. More microleakage occurred in the in vitro
      restorations.

PMID- 8152997
TI  - Class 5 composite resin restorations: margin configurations and the distance from
      the CEJ.
AB  - An in vitro study of 60 teeth examined the cervical microleakage of class 5
      composite resin restorations in regard to preparation design and location from
      the cementoenamel junction (CEJ). Four groups of 15 teeth each were prepared for
      a class 5 composite resin restoration with the cervical margins finished as
      follows: a butt joint margin placed less than 1 mm from the CEJ, a beveled margin
      placed less than 1 mm from the CEJ, a butt joint placed greater than 1.5 mm from
      the CEJ, and a beveled margin placed greater than 1.5 mm from the CEJ. The teeth
      were acid etched, treated with an enamel bonding agent, and restored with a
      microfilled composite resin, and then sectioned for further analysis. The
      sectioned specimens were evaluated for cervical microleakage by Ca45
      autoradiography. The butt joint margins placed less than 1 mm from the CEJ had
      significantly more microleakage than the other groups, indicating that all enamel
      margins of a class 5 composite resin restoration should be beveled to decrease
      microleakage regardless of their location relative to the cementoenamel junction.

PMID- 8152998
TI  - Will the new health care "reform" pediatric dentistry?

PMID- 8152999
TI  - Clinical diagnosis and management strategies of amelogenesis imperfectavariants.
AB  - Amelogenesis imperfecta (AI) is a group of inherited disorders primarily
      affecting dental enamel. Variants of AI generally are classified as hypoplastic,
      hypocalcified, or hypomaturation types based on the primary enamel defect. The
      aim of this study was to analyze the clinical presentations, diagnostic features,
      and clinical complications of different variants of AI. Thirty-two patients from
      17 families with several subtypes of AI were studied. The results showed that
      distinctive clinical features may be observed in each variant. However, all AI
      patients suffered common clinical problems of poor esthetics, teeth sensitivity,
      and loss of occlusal vertical dimension. The mildest problems were found in the
      pitted hypoplastic type whereas the most severe problems were encountered in the
      hypocalcified type of AI. Management strategies include composite resin veneers
      and jacket crowns for anterior teeth as well as steel crowns for posterior teeth.
      Knowledge of the clinical features and dental complications of each variant of AI
      helps in the diagnosis of the condition and allows institution of early
      preventive measures.

PMID- 8153000
TI  - Anterior dental crossbite: relationship between incisor crown length and incisor
      irregularity before and after orthodontic treatment.
AB  - The purpose of this study involving a sample of children with single central
      incisor crossbite was to determine the relationship between clinical crown
      lengths of the crossbite and noncrossbite mandibular incisors, incisor
      irregularity, and orthodontic correction of the crossbite. In addition, for
      comparison, the normal maturational change in position of the labial gingival
      margin of mandibular incisors not undergoing orthodontic correction was examined.
      Twenty-one children treated for single central incisor crossbite were matched
      individually by gender and age to a comparison group. Pre- and post-treatment
      mandibular central incisor crown lengths and incisor irregularity were measured.
      In 10 of the 21 anterior crossbite cases, the crown length of the crossbite
      incisor was more than 1.5 mm greater than that of the noncrossbite incisor. This
      difference improved with orthodontic treatment by a combination of apical
      movement of the gingival margin of the noncrossbite incisor (0.9 +/- 0.8 mm) and
      coronal movement (0.2 +/- 0.6 mm) of the gingival margin of the crossbite
      incisor. In contrast, for the remaining 11 anterior crossbites without such a
      crown length difference, and for the comparison cases, the gingival margins of
      both mandibular central incisors moved equally from pre- to post-treatment by 0.5
      +/- 0.5 mm in an apical direction. Pretreatment crown length difference between
      crossbite and noncrossbite incisor was associated strongly to incisor
      irregularity (P < or = 0.005, r = 0.65). Orthodontic correction of the crossbite
      produced an improvement in irregularity index (IR) that was greatest in those
      anterior crossbite cases with a pretreatment crown length difference.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8153001
TI  - Comparative evaluation of college football officials' attitudes toward NCAA
      mouthguard regulations and player compliance.
AB  - A 12-item questionnaire addressing attitudes of football officials toward the
      1990 National Collegiate Athletic Association (NCAA) mouthguard regulation was
      sent to all officials in the Southeastern Conference (N = 62). The response rate
      was 95% (59). Twenty-seven per cent of officials reported that all players were
      in compliance; 74% believed the new rule to be at least somewhat beneficial in
      determining player compliance, and 20% reported that the rule had resulted in
      more frequent player use. Twenty-two per cent reported they would ignore a
      mouthguard violation and none had charged a time-out or called a penalty during
      the 1991 season. Significant differences in the responses of Big East officials
      surveyed in a previous study were noted by the authors, when compared to the SEC,
      but both groups of officials strongly supported the idea that wearing mouthguards
      should be the responsibility of coaches rather than officials.

PMID- 8153002
TI  - A comparison of pulpectomies using ZOE and KRI paste in primary molars: a
      retrospective study.
AB  - Maintaining a successfully root-treated primary molar has the advantage of
      preserving the natural tooth--the best possible space maintainer. The purpose of
      this study was to compare the success of endodontic treatment of nonvital primary
      molars using ZOE with that of KRI paste. Of 78 necrotic primary molars, 34 were
      filled with ZOE and 44 with an iodoform-containing paste (KRI). The canals were
      prepared with files, rinsed with saline and filled with one of the resorbable
      pastes, using a spiral Lentulo on a low-speed handpiece. A radiograph was exposed
      immediately postoperatively to observe whether the root filling was flush,
      underfilled, or overfilled. The effect of length of fill on the treatment outcome
      also was evaluated. Teeth were examined periodically clinically and
      radiographically to assess success of the treatment. Follow-up interval varied
      from 12 to more than 48 months. Overall success rate for KRI paste was 84% versus
      65% for ZOE, which was statistically significant (P < 0.05). Overfilling with ZOE
      led to a failure rate of 59% as opposed to 21% for KRI (P < 0.02). Conversely,
      underfilling led to similar results, with a failure rate of 17% for ZOE and 14%
      for KRI. These results support the clinical efficacy of root filling with KRI
      paste as a treatment option for nonvital primary molars.

PMID- 8153003
TI  - Orthodontic band retention on primary molar stainless steel crowns.
AB  - The retention of orthodontic bands cemented on primary molar stainless steel
      crowns (SSC) was studied in vitro. Unitek maxillary and mandibular 1st and 2nd
      primary molar SSC were fitted with one of four commonly used orthodontic bands
      (Unitek regular, Unitek narrow, Rocky Mountain, or custom bands made from SSC)
      using glass ionomer cement. The cemented samples were tested for their resistance
      to dislodgment on the Instron Universal Testing Machine (Instron Engineering
      Corp., Canton, MA) in tensile mode. Alpha level for statistical significance was
      set at alpha = 0.05. Unitek regular bands cemented on the 2nd molar crowns and
      Unitek narrow bands cemented on the 1st molar crown samples had equivalent or
      superior resistance to dislodgment compared with the other bands in the study.
      When the inside of the band and the outside band-bearing surfaces of selected
      crowns were lightly scored with a diamond bur prior to cementation, samples
      exhibited significantly superior retention. Subgroup means increased from 107 to
      330%, compared to the values obtained in their preroughened state. The mean
      values obtained using the roughened band/crown interface technique (range 52.9 +/
      7.6 to 73.6 +/- 8.4 lbs) compared favorably with retention values from the
      literature for orthodontic bands cemented on permanent molar and premolar teeth.

PMID- 8153004
TI  - Age dependency of cyclosporin A-induced gingival overgrowth in rats.
AB  - Effects of age on cyclosporin A- (CsA) induced gingival overgrowth were
      investigated in Fischer rats. Rats 15, 30, 45, and 60 days old were fed a diet
      containing cyclosporin A (120-200 micrograms/g) for 40 days. Gingival overgrowth
      was estimated by measuring the gingival sulcus depth with a thin color slide
      probe under a stereoscopic dissecting microscope. The youngest group (15 days
      old) of rats developed the most significant gingival overgrowth (buccal sulcus
      depth of mandibular first molar, CsA-treated rat/untreated rat: 875 +/- 78/275 +/
      25 micron, mean +/- SD, P < 0.001), followed by those in which CsA treatment was
      initiated at age 30 days (505 +/- 29/267 +/- 56, P < 0.001) and 45 days (400 +/-
      45/267 +/- 25, P < 0.001). Significant gingival overgrowth was not induced in
      rats when CsA treatment had been started at age 60 days (310 +/- 38/292 +/- 18).
      Average body weight gain of CsA-treated rats during this experiment period was
      not different from untreated rats of the same age group. These results suggest
      that CsA-induced gingival overgrowth in rats is age dependent.

PMID- 8153005
TI  - Comparison of shear strength, fracture patterns, and microleakage among unfilled,
      filled, and fluoride-releasing sealants.

PMID- 8153006
TI  - Physiologic response and adverse reactions in pediatric dental patients sedated
      with promethazine and chloral hydrate or meperidine.

PMID- 8153007
TI  - Microleakage of Class V composite restorations prepared conventionally with those
      prepared with an Er:YAG laser: a pilot study.

PMID- 8153008
TI  - Acquired condylar hypoplasia: case report.

PMID- 8153010
TI  - Update on board examination results.

PMID- 8153009
TI  - Pharmacologic management of pain, anxiety, and behavior: conscious sedation, deep
      sedation, and general anesthesia.

PMID- 8153011
TI  - Risk scoring systems for identification of infants at high risk of sudden infant
      death syndrome (SIDS) or sudden unexpected infant death (SUD).

PMID- 8153012
TI  - Risk related intervention for SIDS prevention: timely or premature?

PMID- 8153013
TI  - International variations in the incidence of childhood soft-tissue sarcomas.
AB  - In the study of international childhood cancer incidence coordinated by the
      International Agency for Research on cancer, soft-tissue sarcomas comprised
      between 4 and 8% of all cancers between 0 and 14 years of age. Among
      predominantly white populations, the age-standardised annual incidence rate (ASR)
      for all soft-tissue sarcomas was between 5 and 9 per million. The most common
      histological subtypes were rhabdomyosarcoma (ASR 4-7 per million) and
      fibrosarcoma, including other malignant fibromatous tumours (ASR 1-2 per
      million). In the United States the incidence of rhabdomyosarcoma for black girls
      was only half that for white girls, while the rates for boys were similar in the
      two ethnic groups; fibrosarcoma had a higher incidence among black people than
      white people for both sexes. Throughout most of Asia, soft-tissue sarcomas almost
      invariably had a total ASR below 6 per million, rhabdomyosarcoma and fibrosarcoma
      again being the most common histological types. In Africa, incidence rates could
      not generally be calculated, but there were substantial numbers of registrations
      for rhabdomyosarcoma and fibrosarcoma. The majority of cases of Kaposi's sarcoma
      were in African children, and in eastern and southern Africa where Kaposi's
      sarcoma is endemic among adult men it comprised 25-50% of soft-tissue sarcomas
      and 2-10% of all childhood cancers; the sex ratio (M/F) was 2.2:1, in contrast to
      the overwhelming male predominance among adults. Variations between ethnic groups
      in the incidence of rhabdomyosarcoma and fibrosarcoma, together with their
      occurrence in a number of heritable syndromes, suggest that genetic
      predisposition is important in their aetiology. There was little evidence for an
      environmental aetiology in rhabdomyosarcoma and fibrosarcoma but an infectious
      agent may be responsible for childhood Kaposi's sarcoma.

PMID- 8153014
TI  - A high rate of Down's syndrome in two regions of Croatia.

PMID- 8153015
TI  - Fumes from the spleen.

PMID- 8153016
TI  - Ethnic differences in the incidence of the sudden infant death syndrome (SIDS) in
      Victoria, Australia 1985-1989.
AB  - In order to describe ethnic differences in the incidence of the sudden infant
      death syndrome (SIDS) records of all livebirths in the State of Victoria,
      Australia, 1985-1989, excluding those who died in the first month of life, were
      linked to death certificates. Cases were defined as infants dying with a
      diagnosis of SIDS between 1 month and 1 year of age (n = 601) from the cohort of
      308,052 neonatal survivors. Ethnicity was defined by the mother's country of
      birth. The SIDS incidence was 2.04/1000 in infants of Australian-born mothers.
      The relative risk of SIDS was 0.28 (95% confidence interval (CI) 0.15, 0.55) in
      infants whose mothers had been born in Southern Europe and 0.48 (95% CI 0.29,
      0.78) in infants whose mothers had been born in Asia. SIDS in infants of
      Australian-born mothers was associated with low maternal age, high parity,
      marital status other than married, male sex, multiple birth, low birthweight and
      preterm birth. After adjustment for those factors in a case-control analysis
      using a logistic regression model the adjusted odds ratio for SIDS was 0.34 (95%
      CI 0.17, 0.69) comparing infants whose mothers were born in Southern Europe with
      infants of Australian-born mothers, and 0.60 (95% CI 0.35, 1.04) for infants
      whose mothers were born in Asia, compared with infants of the Australian-born.
      Thus there are substantial ethnic differences in SIDS which are not explained by
      the classic social and perinatal risk factors.

PMID- 8153017
TI  - Variations in family visiting policies in neonatal intensive care units in eleven
      EC countries. EC Study Group of Parental Involvement in Neonatal Care.
AB  - The paper addresses the lack of information concerning parental visiting in
      neonatal intensive care units (NICU) across European Community (EC) countries. It
      reports on a study involving 11 EC countries and 38 units carried out under the
      auspices of a Concerted Action project. Information gathered from the 38 units
      yields data on the parental and family visiting policies. The study reveals a
      wide variation in the policies from considerable parental access to the infant in
      the NICU to restricted visiting. Policies concerned with unit facilities and unit
      support staff reflect the orientation of the overall unit policy with regard to
      visiting.

PMID- 8153018
TI  - Gestational age and intrauterine growth retardation among white and black very
      low birthweight infants: a population-based cohort study.
AB  - Very low birthweight (VLBW) is a commonly used endpoint in perinatal
      epidemiology, but the population of VLBW infants comprises a wide range of
      gestational ages and rates of fetal growth. We used data from a population-based
      study of all 1072 black and white VLBW liveborn infants born in 29 counties in
      Georgia between April 1986 and March 1988. Less than 1% of the VLBW infants were
      > or = 37 weeks gestation; most were 29-32 weeks (26%) or 25 to 28 weeks (40%);
      12% were 22 weeks or less. All infants 33 weeks gestation or greater were growth
      retarded. The population of VLBW infants seems to comprise three groups:
      approximately 11% very immature infants of 22 weeks or less; the majority of
      infants, born between 23 and 30 weeks, 90% of which are of normal weight for
      their gestational age; and a group of less premature, growth-retarded infants
      from 31 to 36 weeks. We found little or no difference in the distribution of
      gestational age or the percentage of intrauterine growth rates (IUGR) between
      black and white infants. In the USA the VLBW rate among black infants is over
      three times greater than that among white infants and consequently the rates of
      the three types of VLBW among black infants are likely to be triple those among
      white infants.

PMID- 8153019
TI  - Vaginal bleeding and adverse reproductive outcomes: a meta-analysis.
AB  - The objective of this paper is to characterise and quantify the association
      between vaginal bleeding and pregnancy outcome. A meta-analysis was performed in
      order to quantify the risk of adverse reproductive outcome by combining evidence
      from all previous studies of vaginal bleeding. The reproductive endpoints
      considered were low birthweight, preterm birth, stillbirth, perinatal death and
      congenital malformation. The meta-analysis confirms an association of vaginal
      bleeding with adverse pregnancy outcomes, but identified discrepancies in the
      reported risks of vaginal bleeding and magnitudes of association between bleeding
      and adverse reproductive outcomes, observed across studies. These discrepancies
      may be attributed to inconsistent definitions of the timing and severity of
      vaginal bleeding. The implications of such inconsistencies are discussed,
      suggesting a need for more standardised definitions of vaginal bleeding and
      reproductive endpoints in future studies.

PMID- 8153020
TI  - An epidemiological study of the factors influencing poisoning in children aged 0
      5 years.
AB  - The aim of this cross disciplinary study was to identify the most significant
      variables related to childhood accidental poisoning. The study was carried out on
      a representative sample of families living in the Greater Athens Area comprising
      1245 children aged up to 5 years. Data were collected by a team of researchers
      (paediatricians, psychologists and social workers) and involved a structured
      interview and a paediatric examination. The findings show that childhood
      poisoning is correlated with: (1) biological variables, such as skeletal
      anomalies, language disorders, number of recent infections and complications of
      pregnancy; and (2) social factors, such as father's educational level, monthly
      family income, and overcrowding. Sex of the child was not found to influence
      poisoning.

PMID- 8153021
TI  - Trends in weight-for-height and triceps skinfold thickness for English and
      Scottish children, 1972-1982 and 1982-1990.
AB  - Data from the 1972, 1982 and 1990 surveys of the National Study of Health and
      Growth were used to calculate changes in height, weight, triceps skinfold
      thickness and weight-for-height index for children aged between 4.5 and 11.99
      years. There were data for 7887, 6396 and 6420 white English children in the 3
      years respectively, and data for 1586, 1191 and 1317 Scottish children. Increases
      in all measurements were found from 1972 to 1990, except for weight-for-height in
      English boys, and were generally greater from 1982 to 1990 than from 1972 to
      1982. Approximately a third of the increases in weight-for-height and triceps
      skinfold thickness from 1972 to 1990 were associated with increases in parental
      body mass indices and decreases in family size. No consistent differences in
      trends were found between social groups. Greater trends were found for girls and
      for Scottish children, and Scottish boys are now heavier and fatter than their
      English counterparts. Trends in weight-for-height and fatness may have
      implications for future trends in coronary heart disease, and lessen the
      likelihood that the targets for reductions in obesity in the White Paper Health
      of the Nation will be met. Preventive measures should be directed at the entire
      population.

PMID- 8153022
TI  - Behavioral treatment of panic disorders and agoraphobia.

PMID- 8153023
TI  - Strategies for helping parents of children with conduct disorders.

PMID- 8153024
TI  - Behavioral interventions to reduce stereotypic behaviors of persons with visual
      impairments: a methodological review and critical analysis.

PMID- 8153025
TI  - Assessing and treating parent-adolescent conflict.

PMID- 8153026
TI  - Behavioral medicine with military veterans.

PMID- 8153027
TI  - The personality of the patient: going beyond the trait concept.
AB  - The concept of dominance is a key concept in reversal theory and distinguishes
      the theory from traditional trait theories in personality psychology. By
      dominance is meant the individual's tendency to spend more time in one rather
      than another of the pairs of opposite emotional or motivational states identified
      in the theory. This is in many ways a more sophisticated concept than that of
      trait. Some psychometric scales that have been developed to measure different
      kinds of dominance are reviewed: the Telic Dominance Scale, the Nijmegen Telic
      Dominance Scale, the Paratelic Dominance Scale, the Negativism Dominance Scale
      and the Personal Orientation Profile. The relevance of the dominance concept is
      discussed in relation to patient management.

PMID- 8153028
TI  - Reversal theory: an introduction.
AB  - The theory of psychological reversals, or 'reversal theory', is a relatively new
      theory of motivation and personality that places emphasis on the inconsistency
      and changeability of human behaviour and experience. The present paper provides a
      general introduction to the theory's principal constructs and assumptions.
      Specific reversal theory concepts outlined here include the notions of
      metamotivational modes, reversals between modes and metamotivational dominance.
      The nature of metamotivational reversals and factors that influence the process
      of reversals are also described. Psychometric and experimental research in
      support of the theory is reviewed. The final section offers a critical evaluation
      of reversal theory and discusses its relevance and applicability in the health
      sciences.

PMID- 8153029
TI  - Taking risks with health.
AB  - Some forms of human behaviour serve no obvious biological need and, in terms of
      the individual's health and well-being, appear to be positively self-destructive.
      Using the conceptual framework provided by reversal theory, this paper examines
      what has become known in the theory as 'paradoxical behaviour'. Three different
      types of paradoxical behaviour--taking part in dangerous sports, participation in
      risky gay sex and problems associated with eating--are the focus of this paper.
      Reversal theory explanations of paradoxical behaviour are proving useful in
      helping to explain why individuals engage in activities potentially harmful to
      their health. Understanding the motivation underlying paradoxical behaviour
      should be of interest to those involved in clinical practice.

PMID- 8153030
TI  - A reversal theory approach to the causes and treatment of stress in professional
      life.
AB  - An interactive model, which takes into account both situation and individual, is
      likely to be most useful in understanding the occurrence of stress in
      professional life. Reversal theory, when applied in the way detailed in the
      present paper, yields just such a model. It also, in the way discussed, provides
      a number of practical strategies for helping professionals identify and develop
      ways of coping with stress, particularly when employed within the context of the
      stress management workshop.

PMID- 8153031
TI  - Reversal theory analysis of relapse crises following smoking cessation.

PMID- 8153032
TI  - Instruments for the assessment of reversal theory states.

PMID- 8153033
TI  - Determinants of injecting insulin in elderly patients with type II diabetes
      mellitus.
AB  - In patients with type II diabetes mellitus blood glucose control may gradually
      worsen despite diet and oral hypoglycaemic agents. We investigated which possible
      factors determine the decision for elderly type II diabetic patients to start
      with insulin therapy in this situation. According to Fishbein and Ajzen an
      attitude-behaviour model was constructed which included the determinants
      intention, attitude, subjective norm and self-efficacy. Fifty-three patients (age
      68 +/- 9 years) participated in the study: 26 already used insulin for 7 months,
      27 were tablet-treated but poorly-controlled (fasting blood glucose > 8.0 mmol/l
      and glycosylated haemoglobin > 8.0%). In both groups of patients, a high
      correlation (r = 0.81, P < 0.001) existed between the intention to and the actual
      start or continuation of insulin therapy. The main factor (70%) explaining the
      intention towards insulin treatment was the subjective norm: patients are guided
      by the opinion of important other persons, especially the treating internist, the
      family physician and the diabetes nurse. Tablet-treated patients reported a
      negative opinion of their physician towards their treatment with insulin.
      Intention to behaviour was also determined by self-efficacy, e.g. expectations
      about the skills concerning injecting insulin. Self-monitoring of blood glucose
      and knowledge about diabetes positively influenced self-efficacy, attitude
      towards and intention to use insulin. Education needs to enforce the subjective
      norm and improve the patient's self-efficacy. A stimulating attitude of the
      treating physician towards insulin therapy is essential.

PMID- 8153034
TI  - Effects of systematic patient education about cough on the consulting behaviour
      of a general practice population.
AB  - In four general practices the effects of systematic patient education on cough
      were compared with four control practices. Intended and unintended contacts for
      cough were defined. In two successive autumn-winter periods, in 62% of 5890
      contacts for cough the intervention could be applied. In spite of the better
      baseline situation in the experimental practices, the percentage of intended
      contacts with the GP increased from 47 to 65% (control group: 28 and 30%,
      respectively, P < 0.01). There was a considerable interpractice variance. For
      methodological reasons a leaflet was sent to all the patients in the experimental
      practices. This possibly also led to a shift in the consulting pattern.

PMID- 8153035
TI  - Preferences for involvement in medical decision-making: situational and
      demographic influences.
AB  - We examined desires to be involved in decisions about one's own medical treatment
      in a sample of 459 health maintenance organization members. Demographic variables
      (age, sex and education level) that have been found to be related to decision
      preferences were also tested. As predicted, respondents expressed a desire to be
      involved in decisions that do not require medical expertise, but had
      significantly lower preferences for involvement in decisions that required
      medical expertise. Younger and better-educated individuals reported a higher
      desire for involvement, but there were no sex differences in preferences. The
      higher desire for involvement in decisions not requiring medical knowledge was
      found both for groups that traditionally have wanted involvement and for those
      that have not. The implications of the results for patient participation in
      decision-making are discussed.

PMID- 8153036
TI  - Learning to cope with asthma: a behavioural self-management program for children.
AB  - An educational training program for children with asthma, aged between 8 and 13
      years, was evaluated in an 18-month randomized, controlled experiment, including
      three follow-up evaluations. The objective of the program is to improve coping
      with asthma in daily life. The program, ten 1-hour sessions, is a combination of
      self-management training and cognitive behaviour therapy in a group, using games
      and learning materials specifically designed for this age group. From 195
      asthmatic children, 112 with inadequate self-management abilities were selected;
      these children were randomly divided into an experimental group and two control
      groups. The results indicated highly significant differences in favor of the
      experimental group on the psychological and medical variables. There were no drop
      outs during the program. The conclusion is that this multi-faceted program is an
      effective method of teaching children how to cope with their asthma and helping
      them to achieve a less anxious and more realistic attitude towards their illness.

PMID- 8153038
TI  - Current options in gallstone management. What to do when symptoms are mild or
      absent.
AB  - Recent advances in our understanding of the natural history of gallstones and the
      introduction of new treatment options have dramatically altered the approach to
      gallstone management. Most patients with cholelithiasis are asymptomatic, and for
      them, expectant management is now recommended by many authorities. This approach
      may also be acceptable for some patients who have only occasional episodes of
      biliary colic. Laparoscopic cholecystectomy is preferred for patients who have
      had repeated episodes of biliary colic or acute cholecystitis and who are
      suitable operative candidates. Nonsurgical options include oral dissolution
      therapy with bile acids, extracorporeal shock wave lithotripsy, and contact
      dissolution with methyl tert-butyl ether. Each has significant limitations but
      may be considered for selected patients with symptomatic gallstones who are not
      candidates for general anesthesia or who refuse surgery. Future improvements in
      nonsurgical therapies may ultimately expand their use.

PMID- 8153037
TI  - The child's adaptation to parental medical illness: theory and clinical
      implications.
AB  - Few resource papers are available to health care providers that address in detail
      the issues faced by children in adapting to serious parental illness. The current
      paper offers a developmental approach to understanding the responses and problems
      of school-age and adolescent children coping with parental medical illness. Four
      developmental issues are considered: security and separation anxiety,
      interpersonal understanding, conceptualizations of illness and death and the role
      of fantasy. Based on these considerations, broad guidelines for clinical
      interaction are suggested for health professionals working with seriously ill
      parents and their children.

PMID- 8153039
TI  - Tick-borne infections. What starts as a tiny bite may have a serious outcome.
AB  - Tick-borne illnesses are being reported increasingly often. Unlike Lyme disease,
      which tends to be indolent, Rocky Mountain spotted fever and ehrlichiosis can
      kill and so must be recognized and treated promptly. These diseases require
      clinical diagnosis, because laboratory confirmation with antibody tests takes too
      long. Tetracycline hydrochloride, doxycycline (Doryx, Vibramycin), or
      chloramphenicol (Chloromycetin) treatment is effective. Other diseases (eg,
      babesiosis, tularemia) are encountered occasionally and can also be fatal but are
      treatable with antibiotics.

PMID- 8153040
TI  - Hoarseness. From viral laryngitis to glottic cancer.
AB  - Hoarseness indicates an abnormality at the level of the glottis. This symptom may
      result from either structural or physiologic disorders. The differential
      diagnosis is lengthy and includes both benign and malignant diseases. History
      taking and physical examination, particularly laryngeal visualization, provide
      key clues. Careful and complete examination is always recommended, because airway
      obstruction can in some situations quickly follow hoarseness.

PMID- 8153041
TI  - What would Cooper do to you? Clinton-lite and Clinton-heavy are not much
      different.

PMID- 8153042
TI  - Common nonarticular syndromes in the elbow, wrist, and hand.
AB  - Nonarticular elbow, wrist, and hand discomfort commonly results from
      periarticular or tendon disorders or nerve entrapment. Physicians with a
      practical knowledge of upper extremity anatomy and mechanics and an awareness of
      the typical features of disease are best equipped to treat these often
      encountered conditions. Therapy is based on an accurate diagnosis and should be
      tailored to each disorder.

PMID- 8153043
TI  - Diabetic gastroparesis. What to do when gastric emptying is delayed.
AB  - Diagnostic evidence or symptoms of gastroparesis develop in about 20% to 30% of
      patients with long-standing diabetes. Diabetic gastroparesis is likely caused by
      autonomic neuropathy involving the nerves that regulate gastric motor function.
      The following are necessary for diagnosis: thorough history taking and physical
      examination to eliminate factors that might further delay gastric emptying;
      esophagogastroduodenoscopy or barium contrast studies to exclude structural
      abnormalities; and a radionuclide gastric emptying study. The three main agents
      available for therapy in the United States are metoclopramide (Maxolon, Octamide,
      Reglan), erythromycin, and cisapride (Propulsid). All have been shown to offer
      benefit in improving gastric emptying and symptoms, although use of
      metoclopramide is limited by a significant incidence of side effects. Surgical
      intervention should be avoided if possible.

PMID- 8153044
TI  - Non-Q-wave myocardial infarction. An incomplete cardiac event requiring an
      aggressive approach.
AB  - Evidence that non-Q-wave myocardial infarction (MI) is an unstable or incomplete
      cardiac syndrome is clear. Morphologic findings, coronary pathoanatomy, in
      hospital complication rates, risk-stratification data, postdischarge mortality
      data, and particularly morbidity data indicate a need for close diagnostic
      evaluation and careful long-term follow-up. Thrombolytic therapy appears to be
      ineffective in patients with non-Q-wave MI. Measures to prevent reinfarction
      during the hospital stay are indicated. Any complication of non-Q-wave MI is an
      indication for cardiac catheterization. All patients with non-Q-wave MI require
      predischarge risk stratification. If they cannot be stratified by clinical or
      electrocardiographic characteristics, exercise stress testing is required,
      preferably with an imaging study. When stratification indicates high risk,
      predischarge cardiac catheterization is required.

PMID- 8153045
TI  - A heart for Mr Delcambre.

PMID- 8153046
TI  - Hidden accountability for healthcare costs.

PMID- 8153047
TI  - Simple clues to diagnosis of hypothyroidism.

PMID- 8153049
TI  - Osteoporosis. Methods to prevent fractures in patients at high risk.
AB  - Persons at increased risk for osteoporotic fracture can be identified by clinical
      assessment and bone-density measurements. General measures (adequate amounts of
      calcium and vitamin D, along with an active lifestyle) can slow the rate of bone
      loss and should be recommended for all patients. Estrogen and parenteral salmon
      calcitonin are approved by the Food and Drug Administration for treatment of
      osteoporosis; these agents prevent bone loss in most patients and produce modest
      increases in bone mass, even in patients with advanced disease. Newer agents,
      such as bisphosphonates, provide additional therapeutic options.

PMID- 8153048
TI  - Treatment of Parkinson's disease. From theory to practice.
AB  - Parkinson's disease responds rather dramatically to levodopa therapy during the
      first several years of treatment. With advancing disease, however, symptom
      control becomes more erratic, and some symptoms may become refractory to
      treatment. The use of selegiline hydrochloride (Eldepryl) has been proposed to
      slow the progression of Parkinson's disease; however, current evidence suggests
      that it is only partially effective at best, and there is no definite proof of a
      neuroprotective effect. Nonetheless, it is a reasonable treatment choice.
      Carbidopa-levodopa (Sinemet) remains the foundation of symptomatic treatment of
      Parkinson's disease. Clinical fluctuations occurring with advancing disease may
      be at least partially controlled by appropriate adjustments in dosage. A direct
      acting dopamine agonist, bromocriptine mesylate (Parlodel) or pergolide mesylate
      (Permax), can be very helpful as adjunctive therapy to smooth these clinical
      fluctuations. Excessive intracellular oxidative stress has been proposed as a
      cause of Parkinson's disease; however, a recent multicenter trial investigating
      the use of high doses of the antioxidant vitamin E showed it to be ineffective.
      Whether other forms of nonspecific antioxidant therapy will prove beneficial is
      open to speculation.

PMID- 8153050
TI  - The dementia syndromes. Distinguishing their clinical differences.
AB  - Dementia is one of the most devastating illnesses that affect the elderly. The
      progressive decline in memory, judgment, intellectual function, and adaptive
      ability places an immense burden on families, healthcare providers, and
      communities. Because advancing age is the leading risk factor for most types of
      dementia, the prevalence of this tragic disorder will increase as the population
      ages. How can primary care physicians help?

PMID- 8153051
TI  - How to fall in love with the sympathetic nervous system.

PMID- 8153053
TI  - Dactinomycin analogues as neurokinin-2 receptor antagonists.
AB  - Dactinomycin has recently been shown to be a competitive neurokinin-2 receptor
      antagonist in addition to its inhibiting action on DNA replication. We
      investigated in the isolated guinea-pig bronchi the action of 3 Dactinomycin
      analogues on the contractions evoked by the selective neurokinin-2 receptor
      agonist [Nle10] neurokinin A(4-10). These analogues included 4,4'-Gly
      Dactinomycin and the single peptide lactone of dactinomycin which are inactive on
      DNA replication and 5,5'-MeLeu-Dactinomycin, which has potent antitumour
      activity. Independently of their known effect on DNA replication, the three
      analogues showed neurokinin-2 antagonistic activity which was lower than for
      Dactinomycin.

PMID- 8153052
TI  - Lactic acid-induced plasma protein extravasation in rat airways by stimulation of
      sensory nerves and NK1 receptor activation.
AB  - Locally applied lactic acid and capsaicin caused extravasation of Evans blue dye
      in trachea, main bronchi and nasal mucosa of anaesthetized rats. In animals
      pretreated with capsaicin to deplete sensory neuropeptides, the lactic acid
      response was abolished in main bronchi and highly reduced in trachea.
      Pretreatment with the NK1 receptor antagonist, RP 67580 (3 mg x kg-1
      intravenously), markedly inhibited the lactic acid-induced extravasation at all
      levels; similar pretreatment with NK2 receptor antagonist, SR 48968 (0.5 mg x kg
      1 intravenously), was ineffective. Locally applied ruthenium red (a transmembrane
      Ca2+ fluxes inhibitor), capsazepine (a capsacin receptor antagonist) and
      diclofenac intraperitoneally (a cyclooxygenase blocker) did not change the lactic
      acid effect, while the capsaicin response was only diminished in bronchi by local
      pretreatment with ruthenium red. In conclusion locally applied lactic acid in rat
      trachea and nasal cavity activated capsaicin sensitive sensory nerve endings
      producing plasma protein extravasation. This reaction was shown to be mediated by
      tachykinins acting on the NK1 receptor through a mechanism which appeared to be
      resistant to capsazepine and ruthenium red and independent of cyclooxygenase
      products. In comparison the effect of capsacin was partially ruthenium red
      sensitive but not influenced by capsazepine.

PMID- 8153054
TI  - Acute toluene exposure increases extracellular GABA in the cerebellum of rat: a
      microdialysis study.
AB  - Effect of acute inhalation exposure of toluene or halothane anaesthesia on
      extracellular levels of gamma-aminobutyric acid (GABA) was monitored within the
      cerebellum of rats by microdialysis. GABA increased during and after exposure to
      toluene (2000 p.p.m., 2 hr) in contrast, halothane had no noticeable effect on
      GABA levels. When tetrodotoxin was added to the perfusion medium basal
      concentrations of GABA decreased to about 74% of control concentrations.
      Extracellular GABA levels did not increase during exposure to toluene when
      tetrodotoxin was added to the perfusion medium. The results indicate that toluene
      increase GABA within the cerebellum by sodium dependent mechanisms, possibly by
      modulating the neuronal input from the mossy fibers to the cerebellar cortex.

PMID- 8153055
TI  - Involvement of P450 1A1 in benzo(a)pyrene but not in benzo(a)pyrene-7,8
      dihydrodiol activation by 3-methylcholanthrene-induced mouse liver microsomes.
AB  - Synchronous fluorescence spectrophotometry for benzo(a)pyrene-7,8-diol-9,10
      epoxide (BPDE)-DNA adducts was used to study the activation pathway of
      benzo(a)pyrene in C57BL/6 mice. Benzo(a)pyrene but not benzo(a)pyrene-7,8-diol
      activation by 3-methylcholanthrene-induced mouse liver microsomes was inhibited
      by a monoclonal antibody (Mab 1-7-1) against CYP1A1/2 suggesting that 1A1
      probably takes part in the first P450 reaction. However, aryl hydrocarbon
      hydroxylase activity, a classical measure of benzo(a)pyrene metabolism, was not
      inhibited by the same concentration of Mab 1-7-1. None of the other antibodies
      used, detecting 2A, 2B, 2C or 2E subfamilies, inhibited the adduct formation.
      Troleandomycin and gestodene, chemical inhibitors of human 3A4, inhibited
      benzo(a)pyrene-7,8-diol activation by 3-methylcholanthrene-induced microsomes to
      some extent only in high concentrations. Although liver microsomes from 3
      methylcholanthrene-induced mice catalyzed the formation of BPDE-DNA in vitro
      clearly more than uninduced microsomes, 3-methylcholanthrene pretreatment in vivo
      decreased the adduct formation in benzo(a)pyrene-treated mice. These results
      emphasize the significance of detoxicating and DNA-repairing pathways in vivo.
      Finally, synchronous fluorescence spectrophotometry for BPDE-DNA measures the end
      point of the three-step activation pathway while aryl hydrocarbon hydroxylase
      measures a one-step hydroxylation. Thus, these methods should be used rather as
      corroborative than mutually exclusive assays.

PMID- 8153057
TI  - Diazepam treatment of pregnant rats differentially affects interleukin-1 and
      interleukin-2 secretion in their offspring during different phases of postnatal
      development.
AB  - Treatment of pregnant Long Evans rats with benzodiazepines was found to cause
      alterations in cellular immune responses in their offspring. We now report on
      changes in interleukin-1 (IL-1) and IL-2 secretion which were analyzed in rats
      from birth until 12 weeks. Time-pregnant rats were treated with diazepam (1.25
      mg/kg/day subcutaneously) from gestational day 14 to 20. Lipopolysaccharide
      stimulated release of macrophage-derived IL-1 by spleen cells, determined on
      D10.G4.1 cells, remained in the control range during the preweaning period
      (postnatal day 6-28), then decreased in prenatally diazepam-exposed offspring,
      significantly in males during the postweaning period (postnatal day 34-61) and in
      both sexes in adults (postnatal day 62-83). Concanavalin A-stimulated release of
      T lymphocyte-derived IL-2 from spleen cells, determined on CTLL-2 cells, was
      reduced in male and female offspring during preweaning (postnatal day 3-28) and
      postweaning (postnatal day 33-55) periods and normalized in adulthood (postnatal
      day 60-84). The percentage of IL-2 receptor expressing (CD25+) cells was
      unaffected. From these and our earlier data it is evident that prenatal exposure
      to low doses of benzodiazepines can result in long-lasting alterations of the
      cytokine network, as indicated by reduced release of TNF-alpha, IL-1, IL-6, IL-2
      and interferon-gamma. The concomitant reduction of peripheral type benzodiazepine
      receptors on macrophages is discussed as a possible link between prenatal
      treatment and disturbed function.

PMID- 8153056
TI  - Effects of remoxipride's metabolites on dopamine D2 receptors and receptor
      functions in the rat.
AB  - The main metabolites of remoxipride formed in rat and man were examined for their
      affinities for the [3H] SCH 23390-labelled DA D1 and [3H]-raclopride-labelled D2
      receptors in rat striatal homogenates. In addition, their effectiveness in
      blocking postsynaptic DA receptor activity in vivo was measured by the use of
      several different test models in the male rat. Phenolic metabolites formed mainly
      in the rat retained (similar to remoxipride) their selectivity for the D2
      receptor with very low affinities for the D1 receptor. The pyrrolidone
      metabolites formed mainly in man showed very low affinities for both the D1 and
      D2 receptors. The ability of the metabolites to block postsynaptic DA receptor
      activity in vivo correlated with their affinities for the D2 receptor. Among the
      metabolites tested, the phenolic compounds FLA 797 (-) and FLA 908 (-) were much
      more effective than remoxipride in inducing catalepsy, which is consistent with a
      higher affinity for [3H] raclopride labelled striatal D2 receptors. However,
      analysis of the effectiveness of the DA receptor blockade (blockade of d
      amphetamine locomotion or DA agonist hypothermia) after intraperitoneal or
      subcutaneous administration suggested that FLA 797 (-)/FLA 908 (-) may only
      contribute marginally to the D2 receptor-blocking activity of remoxipride in the
      rat. This conclusion was further supported by the observation that the atypical
      antipsychotic profile of remoxipride was not mimicked by the active metabolites.
      The weak DA D2 blocking effect of the pyrrolidone metabolites indicated that
      remoxipride is responsible for the clinical action.

PMID- 8153058
TI  - Effect of neomycin and other aminoglycosides on adriamycin uptake in rat
      peritoneal mast cells.

PMID- 8153059
TI  - The opioid receptor binding profiles of ketobemidone and morphine.

PMID- 8153060
TI  - Chemical analysis and nutritional assessment of the less known pulses, Vigna
      aconitifolia (Jacq.) Marechal and Vigna vexillata (L.) A. Rich.
AB  - The seeds of Vigna aconitifolia and Vigna vexillata were analysed for proximate
      composition, minerals, seed protein fractions, amino acids, fatty acids, and
      antinutritional factors. Both the pulses were found to be rich sources of
      proteins and minerals like Ca, Mg, Fe, Zn, and Mn. Vigna aconitifolia seeds
      exhibited fairly high levels of crude lipid. The most limiting essential amino
      acids in both the pulses were the sulphur-amino acids, cystine, and methionine.
      Threonine in V. aconitifolia and phenylalanine and tyrosine in V. vexillata
      occurred in higher quantities when compared with WHO/FAO requirement pattern.
      Oleic acid and palmitic acid in V. aconitifolia and linoleic acid and palmitic
      acid in V. vexillata lipids were found to be the predominant fatty acids. The
      tannin content of both the pulses was negligible compared with the domesticated
      legumes. The other antinutritional factors like total free phenols, L-DOPA and
      haemagglutinating activity were also analysed/assayed.

PMID- 8153061
TI  - Influence of grain quality, heat, and processing time on the reduction of
      aflatoxin B1 levels in 'tuwo' and 'ogi': two cereal-based products.
AB  - During the production of 'tuwo' from laboratory-contaminated corn (AFB1:150
      mcg/kg) and sorghum (AFB1:87.5 mcg/kg) grains, reductions in the aflatoxin-B1
      levels of pastes boiled for 30 min and 60 min were found to be 68.0% and 80.8%,
      respectively. In the preparation of 'ogi' from contaminated corn and sorghum
      grains, reductions of about 72.5% and 71.4%, respectively, were obtained after
      fermentation at ambient conditions. Reconstitution of 'ogi' paste into a porridge
      (akamu) considerably reduced the AFB level.

PMID- 8153062
TI  - In vitro availability of iron from cereal meal with the addition of protein
      isolates and fenugreek leaves (Trigonella foenum-graecum).
AB  - In vitro iron availability was determined from a standard cereal meal (C) with
      and without the addition of protein isolates from bovine milk (BP), groundnut
      milk (GP) and soybean milk (SP). A second set of studies were done to investigate
      the potentially available iron from fenugreek leaves per se and the effect of
      their addition on the available iron from the cereal meal. The potentially
      available iron from the meal increased from 4.91% to 6.73% on the addition of BP.
      The next best enhancer was GP (4.91% to 6.17%). Although the addition of SP
      increased the total iron content of the cereal meal significantly, the percent
      available iron decreased compared to the other milk proteins. The addition of
      fenugreek leaves (100 g/meal) to the meal increased the total iron content of the
      meal significantly (3.24 mg to 9.12 mg) (p < .001), however, the available iron
      was observed to decrease (4.91% vs 4.34%).

PMID- 8153063
TI  - Aluminum contents of the edible portions of the winged bean, Psophocarpus
      tetragonolobus (L.) DC. (Fabaceae): field study and caveat.
AB  - The winged bean, Psophocarpus tetragonolobus (L.) DC has been widely recognised
      as a potentially useful source of protein for tropical regions of the world. A
      neglected aspect of the plants nutritional quality has been the reporting of the
      accumulation of aluminum (Al) in the edible parts of the plant; the leaves, pods,
      seeds and tubers. The accumulation of Al in the plant on acidic tropical soils
      and the implication of Al to human health problems further justified the
      inclusion of Al in nutritional analysis. Field experiments on two varieties of
      the winged bean, the USDA-release Hi-Flyer and an unnamed variety from the
      Phillipines, showed that all edible portions of the plant accumulate Al from high
      to very high levels when compared to an average of usually less than 300 ppm in
      other crop plants. Aluminum accumulation is generally highest in the youngest
      tissues particularly in the young roots with levels recorded as high as 25,000
      ppm and these contents are as high as levels for recognised 'Al accumulators'
      such as the leaves of Pinus and tea. Future improvement breeding programs for the
      winged bean will necessarily require identifying and taking advantage of possible
      variation in Al accumulation between varieties.

PMID- 8153064
TI  - Production, nutritional profiles and storability of 'aadun' and 'kokoro': two
      corn products.
AB  - 'Aadun' and 'kokoro' were produced from maize grains by processes involving
      roasting, kneading, spicing, and frying. 'Aadun' with a moisture content (MC) of
      12.5%, pH 5.3 had the following composition: crude protein, 7.49%; fat, 28.5%;
      total carbohydrate, 60.0%; ash, 3.0% and energy value, 3,600 kcal/kg whilst
      'kokoro' with a MC of 16% and pH 5.1 had, respectively: 6.42%; 22.9%; 66.6%;
      2.84% and 3,550 kcal/kg. Whilst 'aadun' and 'kokoro' stored under ambient
      conditions (28 +/- 2 degrees C; 75-80% RH) became mouldy within 7 days, samples
      treated with 1% butyl paraben did not develop off-colour and mouldiness.

PMID- 8153065
TI  - Quality of rolled barley flakes as affected by batch of grain and processing
      technique.
AB  - Rolled barely flakes were prepared from three different batches of grain by
      pearling, steaming and rolling. Autoclaved and malted barleys from the three
      batches were also processed in the same way. Analysis of the nine products showed
      that both batch of barley and process had significant effects on chemical
      composition and viscosity. Puddings were prepared from the products and
      mechanical consistency, juiciness and grain consistency were graded on both newly
      prepared and heated puddings by a sensory taste panel. Batch of barley had no
      effect on mechanical consistency but significant effects on juiciness and grain
      consistency. Type of processing had significant effect on all three parameters
      for both newly prepared and heated puddings.

PMID- 8153066
TI  - Production and storage stability of non alcoholic banana beverage powder.
AB  - Powder for an instant, non-alcoholic beverage formulation was manufactured by
      sundrying and ovendrying of a popular dessert ('silk') banana variety. The
      reconstituted beverage was organoleptically acceptable. The effect of traditional
      sundrying on mats and ovendrying methods on product quality was investigated.
      Sundrying resulted in losses of Vitamin A, C and total sugar contents by 74, 91
      and 63%, while ovendrying losses were 73, 90 and 62%, respectively. Nutrient
      losses during storage for three months in transparent polythene bags reached 93,
      93 and 70% in sundried samples and 84, 99 and 55% in ovendried samples,
      respectively. The moisture content of sundried and ovendried samples increased by
      12 and 17%, respectively, during storage. The increase in microbial load in this
      period was higher in sundried samples.

PMID- 8153067
TI  - In vitro starch and protein digestibility and iron availability in weaning foods
      as affected by processing methods.
AB  - In the present investigation, four weaning foods were formulated using locally
      available cereals and pulses such as wheat (Triticum aestivum), barley (Hordeum
      vulgare) and green gram (Vigna radiata). Cereal, pulse and jaggery were used in
      the proportion of 70:30:25. Domestic processing technique like roasting and
      malting were used to process cereals and pulses for development of weaning foods.
      All the four blends had a nutrient composition within the range prescribed by the
      Indian Standard Institute (ISI) for processed weaning foods. The processing of
      grains resulted in 16-20% increase in starch digestibility and 17-32% increase in
      protein digestibility. Also 16-32% increase in iron availability was observed on
      processing. The effect was more remarkable in malted weaning foods as compared to
      roasted ones.

PMID- 8153068
TI  - Nutritional profile and antimicrobial spectrum of the spice Aframomum danielli K.
      Schum.
AB  - The spice, Aframomum danielli, on a wet weight basis with a moisture content of
      10.5%, protein content of 8.2% (dry matter basis) and caloric value of 469.7
      kcal/100 g, contains in varying amounts, minerals like calcium, magnesium,
      sodium, manganese, phosphorus, zinc and copper. Amino acids found in varying
      concentrations in A. danielli include L-Threonine, L-Serine, L-Valine, L-Proline,
      L-Glutamic acid, glycine, L-Leucine and L-Lysine. Using minimum inhibition zone
      of 20-22 mm in diameter, A. danielli inhibited the growth of Salmonella
      enteriditis, Psudomonas fragi, Pseudomonas fluorescens, Proteus vulgaris,
      Streptococcus pyogenes, Staphylococcus aureus, Aspergillus flavus, A.
      parasiticus, A. ochraceus and A. niger. The minimum concentration (MIC)
      determined for Klebsiella pneumoniae and Pseudomonas aeruginosa was 1 in 320
      whilst the MIC for S. aureus was 1 in 8,000.

PMID- 8153069
TI  - Microbiological evaluation of tofu and tempeh during processing and storage.
AB  - Tofu samples consisting of 'Fresh Tofu', 'Herb Tofu', 'Tofu Paste', 'Fried Tofu',
      'Tofu Burger', 'Smoked Tofu' and different types of herbs used for making 'Herb
      Tofu' were analysed for their microbiological load. Tempeh samples consisted of
      cook water, inoculated beans and fresh tempeh. 'Fresh Tofu' and 'Herb Tofu' had
      high bacterial counts (> or = 10(5) cfu/g). 'Tofu Burger' and 'Smoked Tofu' had
      counts around 10(4) cfu/g. 'Tofu Paste' and 'Fried Tofu' had low counts (< 10(2)
      cfu/g). Cutting board, knife and frequent hand contact with product were the
      major sources of contamination for tofu. Herbs used for making 'Herb Tofu' were
      highly contaminated (> 10(5) cfu/g). Cook water and cooked beans for tempeh
      production had lower counts (< or = 10(4) cfu/g). Initial count of fresh tempeh
      was high (about 10(8) cfu/g). Most products had counts of > 10(6) cfu/g after 7
      days of cold storage. The microbiological quality of the product may improve if
      producers avoid unnecessary contamination during processing.

PMID- 8153070
TI  - Changes in the carbohydrates and nitrogenous components during germination of
      proso millet, Panicum miliaceum.
AB  - Since germination has been found to increase the nutritive qualities of grains,
      proso millet, a minor millet, was allowed to germinate for 1-7 days and analysed
      for protein fractions, free amino acids, lysine, tryptophan, methionine, non
      protein nitrogen, starch, and sugars. Overnight soaking and germination up to 7
      days significantly increased the free amino acids and total sugars while the
      content of dry weight and starch decreased. Increases in albumin and globulin and
      large decreases in prolamin accompanied sprouting. The percent protein in
      germinated grains was higher than in the initial grain as a result of dry matter
      loss during germination. Further, there was an increase in lysine, tryptophan and
      non-protein nitrogen contents during germination. No change was noticed in
      methionine content.

PMID- 8153071
TI  - [Presentation of the 3-dimensional spongiosa structure of the spine in renal
      osteopathy after chronic hemodialysis].
AB  - Characteristic skeletal changes occur in patients with chronic renal
      insufficiency. The aim of this study was comprehensively to record bone volume
      changes in the spine, from C2 to L5, after a long history of hemodialysis. The
      spinal columns of nine autopsy cases who had undergone 4 to 15 years of dialysis
      were thoroughly examined. The age-related control group consisted of 26 autopsy
      cases with intact skeletons. A iliac crest biopsy facilitated a direct comparison
      of the diagnostic biopsy location and the spinal column. A newly developed
      preparation technique enables a combined two- and three-dimensional analysis to
      be made, so that in addition to the histologic image, the directly underlying
      three-dimensional structure can be analyzed. The spine deformity index (SDI), the
      bone volume (BV/TV), and the trabecular interconnection (TBPf) was quantitatively
      evaluated. The SDI shows vertebral fractures in renal osteodystrophy (ROD) types
      I and II in spite of a trabecular bone volume within normal limits. The
      trabecular bone volume shows a distribution throughout the spinal column familiar
      from the skeletally intact control group. The plateau-like curve line, decreasing
      from the cervical spine to the lumbar spine is, however, 5% lower in ROD. BV/TV
      values of 51.2% and 74.1% in the 2nd lumbar vertebra are clearly lower than in
      the corresponding iliac crest biopsy. Cases with a longer history of hemodialysis
      show higher BV/TV values irrespective of age and sex. Normal BV/TV does not mean
      physiological linking. Three-dimensional analysis in ROD shows, in comparison to
      the controls, a much stronger restructuring of the architecture than can be
      assumed from the two-dimensional histological sections.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8153072
TI  - [Differential diagnosis of synovitis. Correlation of arthroscopic-biopsy to
      clinical findings].
AB  - Histological examination of 1660 biopsies (2-5 mm) of the synovial membrane of
      317 patients were obtained by arthroscopic dissection; in 70% of all cases non
      specific changes were revealed and in 30% specific changes. The findings included
      different stages of proliferation of the superficial layer, uncharacteristic
      inflammatory reactions of the stratum synoviale and fibrosis of the stroma,
      vascular proliferation and pseudopolypoid thickening of the synovial membrane.
      The histomorphological findings can only be interpreted reliably and a
      pathogenetic classification obtained, e.g., detritus synovialitis, rheumatoid
      arthritis or post-traumatic changes, if the arthroscopic findings conclude an
      exact documentation of the biopsy site and the clinical findings.

PMID- 8153073
TI  - [Pathologic embryo examinations of induced and spontaneous abortions in the 1st
      trimester of pregnancy].
AB  - Morphological examination methods which are appropriate for detection of
      embryonic developmental defects are presented. The main emphasis is put on
      autopsy of small embryos using a dissection microscope and on documentation of
      the embryonic skeleton by means of skeleton staining. Through presentation of the
      embryopathological findings in 15 first-trimester abortion specimens we
      demonstrate that these examination techniques frequently allow diagnosis of
      isolated malformations as well as malformation syndromes, even in the fragmented
      or macerated embryo. Careful embryopathological examination and evaluation is a
      precondition for genetic counselling, as well as for goal-directed prenatal
      diagnostic measures in future pregnancies.

PMID- 8153074
TI  - [Granulomatous endocarditis caused by streptococcus].
AB  - Two cases of granulomatous endocarditis are reported. The patients developed
      aortal endocarditis refractory to antibiotics. Therefore, aortal valve
      replacement was performed. In both cases, Streptococcus viridans was demonstrated
      in culture and bacterioscopically to be the cause of infection. Histological
      examination of the valves showed characteristic endocarditis with fibrinoid
      necrosis and histiocytic granulomas. Streptococci were found in the cytoplasm of
      macrophages. The possible causes of this special form of infectious endocarditis
      are discussed.

PMID- 8153075
TI  - [Systemic karyomegaly with chronic interstitial nephritis. Discussion of the
      disease picture based on an autopsy case].
AB  - Systemic karyomegaly associated with interstitial nephritis was first described
      in 1978 by Mihatsch. Seven cases have been reported to date. We give an account
      of an autopsy case of systemic karyomegaly in a 30-year-old Italian man. Bizarre
      enlargement of nuclei was found in renal tubular epithelial cells, Schwann cells
      and in smooth muscle cells of vessels and bowel and, less obviously, in
      endothelial and adventitial cells of vessels, in alveolar epithelial cells and in
      astrocytes of the brain. These findings were associated with chronic interstitial
      nephritis, nonspecific hepatopathy, adenocarcinoma of the rectum and multiple
      sclerosis. The clinical course was marked by chronic renal failure, chronic
      haemodialysis and renal transplantation. The patient died 8 years after diagnosis
      in septic-toxic shock. The aetiology and pathogenesis of the disease are
      discussed.

PMID- 8153076
TI  - [Plexiform fibrohistiocytic tumor. Histology, immunohistology and
      ultrastructure].
AB  - An example of a plexiform fibrohistiocytic tumour (PFT) is presented for the
      first time in the German-language literature. The diagnostic criteria for this
      rare soft-tissue neoplasm of childhood and young adulthood, which is mostly
      subcutaneous in location and has a tendency to recur, include the plexiform
      structure which gives it its name, extensive siderin deposits and numerous
      osteoclast-like giant cells. The development of the tumour described here, which
      occurred in the field of radiation of a malignant haemangiopericytoma excised 7
      years previously, indicates the possibility of induction of PFT by radiation.

PMID- 8153077
TI  - [Pathology of rheumatoid lung].
AB  - In the framework of rheumatic illnesses, the lungs and pleura are often observed
      to be involved. Dependent on the basic illness in question, conditions of the
      bronchoalveolar system, vessels, lymphatic system, and pleura that have developed
      differently inter- and intra-individually can be diagnosed in topo-regionally
      variable forms and combinations. In the causal pathogenesis, the initial (auto-)
      immunological alteration of the alveolar septa plays a role. When the monocytes,
      macrophages, and fibroblasts are activated, as a result of a chronic inflammatory
      process there is increasing reparative proliferation, which finally leads to the
      non-specific end stage of irreversible interstitial fibrosis. The incidence and
      manifestation forms of lung changes show certain differences dependent on the
      underlying illness (e.g., rheumatoid arthritis, systemic lupus erythematosus,
      progressive systemic scleroderma, dermatomyositis and polymyositis, Sjogren
      syndrome, and mixed connective tissue disease). In addition to vasculitis and
      granulomatosis of the lung, therapy-induced lung changes must also be considered
      in the differential diagnosis since almost all basic therapeutic agents can cause
      this type of lung condition. Good knowledge of the parameters from the viewpoint
      of possible therapeutic measures is indispensable, as is close cooperation
      between the treating physician and the pathologist.

PMID- 8153078
TI  - [Rhabdomyosarcoma of the liver in adulthood. Case report and review of the
      literature].
AB  - Primary sarcomas of the liver are rare, and hepatic rhabdomyosarcomas are usually
      confined to early childhood. They are mostly related to large bile ducts of the
      liver hilus. We report a case of primary hepatic pleomorphic rhabdomyosarcoma in
      a 69-year-old man.

PMID- 8153079
TI  - [Explosive metastasis of a cancer of the kidney pelvis in analgesic kidney].
AB  - A 48-year-old male experienced sudden pain in the right flank and macrohematuria
      with subsequent repeated episodes of painless macrohematuria. In the radiological
      work-up, CT was interpreted as inflammatory enlargement of the right kidney and
      MRI diagnosed renal vein thrombosis. There was some suspicion that there might be
      a malignancy. Five months later the patient had to be admitted to the hospital,
      because of increasing flank pain, desiccation and general signs of inflammatory
      disease. Radiological changes compatible with pulmonary metastases were found.
      Biopsy of enlarged mediastinal lymph nodes revealed undifferentiated carcinoma.
      Because of the expression of Cytokeratin primary urothelial carcinoma was
      suspected. The patient then deteriorated rapidly. No further specific therapy
      could be carried out. Death was chiefly caused by respiratory insufficiency 5
      months after the first episode of pain and 1 month after admission. Autopsy
      revealed a poorly differentiated urothelial carcinoma of the right renal pelvis,
      with extensive carcinomatous angiomatosis and metastases to the left kidney,
      lungs, and regional and mediastinal lymph nodes. Independently of the carcinoma,
      both kidneys also showed interstitial nephritis, papillary necrosis and
      capillarosclerosis, compatible with analgesic-user kidney ("phenacetin kidney")
      in the absence of a corresponding history.

PMID- 8153080
TI  - [Comments on the contribution by S. Presse et al. Morphology of bladder cancer
      based on cystectomy specimen].

PMID- 8153081
TI  - [Comments on the contribution by C. Kainz et al. Human papillomavirus infections
      and carcinoembryonal antigen expression in cervix intraepithelial neoplasms of
      intermediate grade].

PMID- 8153082
TI  - [The 50th anniversary of the death of Ludwig Pick (1868-1944)].

PMID- 8153083
TI  - Current topic: oxygen exchange in the chorioallantoic membrane, avian homologue
      of the mammalian placenta.

PMID- 8153084
TI  - Mechanism of interleukin-1 beta stimulation of human amnion prostaglandin
      biosynthesis: mediation via a novel inducible cyclooxygenase.
AB  - We have evaluated the mechanism by which interleukin-1 beta (IL-1 beta) increases
      amnion cell PGE2 production in a concentration-dependent manner. IL-1 beta
      stimulated amnion cell PGE2 biosynthesis was time-dependent, and significant
      stimulation occurred within 2 h of incubation. IL-1 beta stimulation occurred in
      the presence of added arachidonic acid but was abrogated by treatment with
      cycloheximide and actinomycin D. Amnion cells treated with IL-1 beta recovered
      rapidly from aspirin pretreatment suggesting an action on fatty acid
      cyclooxygenase (COX). Increased amounts of COX protein were demonstrated by
      Western blot analysis within 2 h of IL-1 beta treatment of amnion cells. Northern
      blot analysis using a probe specific for a novel form of COX (COX-II) showed an
      increase in mRNA for this COX within 30 min. This finding using a homologous
      detection system and human cells of fetal origin in primary culture provides
      strong support for a physiological role for COX-II in man.

PMID- 8153085
TI  - Effect of the choline acetyltransferase inhibitor (2-benzoylethyl)
      trimethylammonium iodide (BETA) on human placental prostaglandin release and
      phospholipase A2 activity.
AB  - We investigated the effect of an inhibitor of acetylcholine (ACh) synthesis, (2
      benzoylethyl)trimethylammonium iodide (BETA), on prostaglandin (PG)E2 and PGF2
      alpha release from incubated placental explants in the presence or absence of ACh
      or arachidonic acid (AA). BETA alone (100 microM) significantly reduced both PGE2
      and PGF2 alpha release. However, this inhibitory effect of BETA was not reversed
      in the presence of ACh (10 microM to 1 mM). The addition of AA (10 to 100 microM)
      increased both PGE2 and PGF2 alpha release, and simultaneously overcame the
      inhibition of PGE2 but not PGF2 alpha release by BETA. These results are
      compatible with the hypothesis that BETA may be inhibiting the phospholipase A2
      (PLA2) step rather than prostaglandin H synthase (PGHS) step in the enzymatic
      pathway of PG generation. This hypothesis was supported by evidence showing a
      lack of effect of BETA (10 and 100 microM) on ovine placental microsome PGHS
      activity. Moreover, human placental homogenate PLA2 activity was reversibly
      inhibited by BETA (100 microM). In the presence of BETA (100 microM), addition of
      exogenous ACh (100 microM) had no significant effect on placental PLA2 activity.
      These results indicate that the inhibitory effect of BETA on placental PG release
      was unlikely to be via an action on ACh synthesis, but rather via a reversible
      effect on PLA2 activity.

PMID- 8153086
TI  - Localization of bovine trophoblast protein-1 in the cow blastocyst during
      implantation: an immunological cryoultrastructural study.
AB  - At implantation in ruminants the signal for maintenance of progesterone
      production by the corpus luteum, essential for a successful pregnancy, is an
      interferon-like protein (bovine, ovine or caprine trophoblast protein-1; e.g. bTP
      1) produced by the blastocyst trophoblast. This quantitative immunogold
      cryoultrastructural study demonstrates that bTP-1 immunoreactivity is found only
      in the Golgi complex and associated clear vesicles in the uninucleate trophoblast
      cells between 18 and 23 days post insemination. The characteristic trophoblast
      binucleate cells (up to 20 per cent by number) show no significant label at any
      time. There is also some evidence for transient labelling of the fetomaternal
      microvillar junction at the time of maximum bTP-1 production suggesting a
      transfer of the molecule by exocytosis. No evidence for any labelling within the
      uterine epithelium was observed.

PMID- 8153087
TI  - Differential secretion of prostaglandin E and prostaglandin F2 alpha by ovine
      uninucleate trophoblast cells in vitro.
AB  - We have previously shown that ovine uninucleate trophoblast cells maintained in
      serum-free medium on Matrigel-coated filters in dual-compartment culture chambers
      retain morphological polarity similar to that found in vivo. The present study
      was undertaken to determine the time course of tight junction formation between
      these cells in vitro and to characterize their basal release of prostaglandin E
      and F2 alpha. Trophoblast cells were purified from ovine placentomes obtained at
      117-124 days of gestation and maintained in culture for up to 10 days. On each
      day of culture, the permeability of the cell monolayers to 3H-inulin and the
      secretion of prostaglandin E and F2 alpha were determined. Minimum permeability
      of the cell monolayers was reached by day 4 of culture, indicating that tight
      junction formation was complete by this time. Following an initial decrease,
      prostaglandin release by the trophoblast cells stabilized on days 6 to 8 of
      culture. On these days, prostaglandin E was secreted in equal amounts into the
      apical and basal compartments of the culture chamber. There was, however, 3.5
      times more prostaglandin F2 alpha secreted into the apical chamber than the basal
      chamber at this stage of culture. These findings confirm the functional polarity
      of ovine trophoblast cells in culture and demonstrate differential secretion of
      prostaglandin E and F2 alpha by these cells.

PMID- 8153088
TI  - Analysis of pregnancy-associated major basic protein levels throughout gestation.
AB  - Previous studies have shown that MBP levels rise before labour and have suggested
      the use of pMBP levels as a predictor of labour. We hypothesize that pMBP levels
      show a common pattern in pregnant women including a late third trimester rise in
      pMBP which predicts the onset of labour. Serum pMBP levels were measured
      throughout gestation in 112 pregnant women. We then analysed the relationship of
      pMBP levels to the time of labour onset, and to other features of pregnancy. An
      exponential increase in pMBP levels was seen early in gestation from weeks 5 to
      21 in all pregnant women. In total, 79 per cent of the women showed rises in pMBP
      of > or = 25 per cent above baseline during the third trimester. pMBP levels were
      shown to be associated with placental weight, multiple gestation, and parity.
      pMBP levels could not, however, be used to form a precise model for the
      prediction of labour. The role of pMBP in pregnancy remains unclear.

PMID- 8153089
TI  - Norepinephrine regulates human chorionic gonadotrophin production by first
      trimester trophoblast tissue in vitro.
AB  - The effect of norepinephrine (NE) upon human chorionic gonadotrophin (hCG)
      production by 6-8 week gestation placental explants has been investigated. NE (5
      micrograms/ml) enhanced hCG secretion significantly from the second day of
      treatment. The stimulatory effect of NE on hCG secretion could be abolished by
      the alpha 1-receptor specific antagonist prazosin (10(-4) M) and partly
      diminished by the beta 1-receptor specific antagonist atenolol (10(-4) M), but
      was not influenced by the alpha 2-receptor specific antagonist yohimbine (10(-4)
      M). The involvement of the alpha-receptor in the regulation of hCG secretion was
      further confirmed by addition of the alpha-receptor agonist clonidine (10(-6) M)
      which had a similar stimulatory effect on hCG release but the effect was
      antagonized by both prazosin and yohimbine. Further study showed that NE induced
      a significant increase in cyclic adenosine monophosphate (cAMP) production by
      trophoblast tissue. Cyclic AMP secretion in the NE-treated group was fivefold
      higher than that of the control group. Both the protein kinase C (PKC) specific
      activator 1-deoyl-2-acetyl-sn-glycerol (OAG) and the PKC non-specific activator
      phorbol-12-myristate-13-acetate (PMA) had a stimulatory effect on hCG secretion,
      while the PKC inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H7)
      diminished the hCG secretion stimulated by NE. The effect of NE was blocked by
      the voltage-dependent calcium channel blocker nifedipine but not by the voltage
      independent calcium channel blocker gadolinium chloride (GdCl3). On the other
      hand, anti-gonadotrophin releasing hormone (GnRH) IgG and the GnRH antagonist (D
      Phe2, D-Trp6)-GnRH did not influence the stimulatory effect of NE on hCG release.
      The results indicate that NE regulates hCG production in human first trimester
      trophoblast tissue. The effect of NE was mainly mediated by alpha 1 and partly by
      beta 1 receptors. Cyclic AMP, the PKC signal transduction pathway and the voltage
      dependent calcium channels were involved in NE action.

PMID- 8153090
TI  - Regional distribution of the angiotensinogens in human placentae.
AB  - Angiotensinogen is the substrate for the enzyme renin. In addition to the well
      characterized low molecular weight forms of angiotensinogen, a high molecular
      weight form (HMrA) comprises about 15 per cent of the total angiotensinogen in
      plasma of pregnant women. In the current study the different forms of
      angiotensinogen were quantitated in different regions of the placenta. The
      highest concentration of total angiotensinogen was found in the chorion laeve
      followed by the amnion. It was found that HMrA was the major form of
      angiotensinogen in all regions of the placenta, accounting for 72, 67, 63, and 59
      per cent of the total angiotensinogen in the chorion laeve, chorion plate,
      amnion, and chorion frondosum, respectively. There was a significant correlation
      between the distribution of total renin and HMrA. This data in conjugation with
      previous data indicate that HMrA should be considered a significant component of
      the renin angiotensin system in the human pregnant state. It is suggested that
      HMrA may be a component of a tissue specific renin angiotensin system that occurs
      in the placenta.

PMID- 8153091
TI  - Differential expression of laminin, nidogen and collagen IV genes in the
      midgestation mouse placenta.
AB  - The distribution of laminin A, B1, B2, nidogen and collagen alpha 1(IV) mRNA was
      studied in the 12.5-day mouse placenta and uterus. This was compared to the
      pattern of laminin, nidogen and collagen IV immunoreactivity in the placenta at
      this time. High levels of B2 mRNA were distributed throughout the decidual layer,
      compared to lower levels of laminin B1, nidogen and collagen IV. In contrast,
      laminin B1 and nidogen mRNA were found at very high levels in the trophoblast
      giant cells and cytotrophoblast. Laminin B2 was much lower in trophoblast cells
      than in the decidua. Nidogen mRNA levels were low in the decidual cells, but high
      in endothelial cells lining the placental blood spaces in the decidual layer.
      Immunofluorescence staining of the placenta showed colocalization of laminin,
      nidogen and collagen IV in fetal and maternal layers of the placenta. In the
      antimesometrial area where the uterine epithelium was reforming laminin B1 and B2
      mRNA were uniformly distributed between the epithelium and stroma, whereas
      nidogen and collagen alpha 1(IV) mRNA were only produced by the stromal cells. In
      all cell types, apart from parietal endoderm cells forming Reichert's membrane,
      laminin A chain mRNA was very low or absent. These results demonstrate that
      laminin and nidogen genes are not coordinately expressed in the midgestation
      mouse placenta. Comparison of the distribution of these mRNAs with collagen alpha
      1(IV) mRNA suggests that different regions of the placenta produce specialized
      extracellular matrices which may contain different ratios of these polypeptides.

PMID- 8153092
TI  - [Influence of nCPAP therapy on bradycardic arrhythmias in sleep apnea].
AB  - In 5-10% of patients with sleep apnoea, AV conduction block or sinus arrest up to
      several seconds can be demonstrated. We studied the effect of nCPAP treatment on
      apnoea-associated heart blocks. 10 consecutive patients (9 m, 1 f) between 28-56
      years of age (mean value 43.4 y) were studied. The diagnosis of sleep apnoea and
      nocturnal heart blocks during the first visit at the outpatient department were
      the only selection criteria. A standard polysomnography before and during nCPAP
      was performed. Mean pretreatment RDI was 91/h. Repetitive II degrees and III
      degrees AV conduction blocks were diagnosed in 2 patients (pts) and sinus arrest
      of 2 to 11 s in 8 pts at the study without therapy. 89.2% of heart blocks
      occurred during REM-sleep. In 8 pts a complete reversal of heart blocks could be
      demonstrated during nCPAP. In 2 pts heart blocks persisted at a reduced number
      during REM-sleep, mainly during ineffective nCPAP. In 80% of our pts nCPAP leads
      to a complete reversal of heart blocks. The indication for pacemaker implantation
      must be established on an individual basis.

PMID- 8153093
TI  - [Inspiratory intrathoracic pressure changes in obstructive and mixed sleep
      apnea].
AB  - Oesophageal pressure swings were analysed during complete occlusion of the upper
      airways in 8 patients with obstructive sleep apnoea. We hypothesed that in
      dependence of the apnoea type, there is a significant decrease in oesophageal
      inspiratory effort in REM vs. NREM that is caused by a decrease of the
      respiratory drive. We analysed in each patient 40 apnoeas in which the
      respiratory timing (Ti) and the inspiratory effort (Pin) were calculated and
      compared with the type of apnoea and the degree of oxygen desaturation. A
      significant decrease in inspiratory effort in REM vs NREM occurred only in mixed
      apnoeas but not in patients with mainly obstructive apnoeas. Additionally, all
      apnoeas with a decrease of inspiratory effort at the end of apnoea during NREM
      were seen in obstructive apnoeas only, whereas none occurred in mixed apnoeas.
      Due to the significant lower inspiratory timing during obstructive apnoeas vs
      mixed apnoeas we assume a decrease in respiratory drive in the patients suffering
      mainly from obstructive apnoeas.

PMID- 8153094
TI  - [Therapeutic consequences of obstructive sleep apnea syndrome--results of drug,
      mechanical and surgical treatment].
AB  - The therapeutical strategy of the obstructive sleep apnoea syndrome depends on
      the differential diagnosis of the sleep disorder, the subjective complaints and
      the patients' individual cardiopulmonary risk profile. Basic requirements for a
      successful treatment are stepped concepts for therapy. Initial therapeutical
      methods are preventive measures such as adequate sleep hygiene, weight loss, and
      reduction of alcoholic intake. We investigated the effectiveness of following
      therapeutical methods: drug treatment, nasal CPAP therapy and surgical approach.
      We present the results of the first 151 treated patients aged between 15 and 88
      years (mean: 50.8 +/- 11.5 SD). 20 patients with an apnoea index below 20 per
      hour were treated with theophylline. After 4 weeks with theophylline there were
      no significant changes in apnoea index, O2 saturation and snoring level. 24
      patients themselves preferred the Uvulopalatopharyngoplasty (UPPP). 8 weeks after
      surgical approach we couldn't find significant changes in the apnoea index
      although 11 of these patients reported on a better sleep quality. 107 patients
      were treated with nasal CPAP. The effective CPAP pressures were between 6 and
      14.5 mbar. Long term compliance with CPAP was studied in a survey of 70 patients
      who underwent a CPAP trial. After 6 months 97% were complaint, 17% of them
      additionally were using a humidifier. Our data show that effective therapy can be
      achieved with nCPAP objectively and subjectively. Other methods--theophylline and
      UPPP--are less successful. CPAP is likely to remain the first choice for
      treatment of sleep related breathing disorders and it should be applied more
      generously.

PMID- 8153095
TI  - [Spectral analysis of long-term blood pressure measurements in patients with
      sleep-related respiratory disorders].
AB  - Spectral analysis of long-term recordings of blood pressure is a convenient
      method to recognise and reveal the amplitude and periodicity of changes in blood
      pressure during sleep. The increased variability of nocturnal blood pressure in
      patients with sleep apnoea is mainly determined by two types of oscillating
      variations in blood pressure: 1. Oscillations in a low frequency range of 0.0
      0.06 Hz associated with breathing disorders and consecutive arousals. 2.
      Oscillations in a higher frequency range of 0.2-0.5 Hz associated with three
      different patterns of breathing. Normal undisturbed breathing, regular snoring
      and ineffective breathing efforts during obstruction of the upper airways.
      Furthermore, the interaction between breathing or breathing disorder and arterial
      blood pressure is determined by the influence of the sleep stages.

PMID- 8153096
TI  - [Non-invasive, continuous, portable blood pressure recording in the sleep
      laboratory].
AB  - The importance of cardiovascular consequences of sleep related breathing
      disorders implies the need for continuous recording of blood pressure in any
      cardiorespiratory polysomnography. Invasive techniques, which are the gold
      standard, are limited to special indications and studies. Non-invasive,
      continuous methods opened new possibilities for sleep laboratory investigations.
      The existing Finapres system proved to be a valuable method if parallel video
      recording was applied. The size of the system restricts its application to
      stationary settings only. Therefore the methodology was improved and integrated
      in a portable recorder. A prototype of this recorder, the Portapres, was
      validated against invasive pressure in 9 one-hour tests during the day and 12
      polysomnographic recordings of 8 hours duration. The Portapres has now two finger
      cuffs and an automatic hydrostatic height compensation to overcome limitations of
      the Finapres. The technical implementation of the recorder needs more
      improvements. The correlation of mean blood pressure was 0.81 and mean pressure
      of the Portapres was 6.8 mmHg lower than invasive values.

PMID- 8153097
TI  - [Incidence of obstructive sleep apnea syndrome in combination with chronic
      obstructive respiratory tract disease].
AB  - Polysomnographic measurements were performed in 210 indoor patients (age mean =
      49.7 +/- 8.9 years, Broca mean = 126.0 +/- 20.7% FEV1%p mean = 79.9 +/- 23.9) of
      a pneumological rehabilitation centre who had a suspicious history or clinical
      symptoms of obstructive sleep apnoea. 72 had neither an airway obstruction nor a
      pathological apnoea index. 58 patients only suffered from airway obstruction and
      42 had only a pathological apnoea index. In 38 patients, a pathological apnoea
      index and also airway obstructions were seen. For the last three groups we
      calculated the mean of the SaO2-values for an 8 hour night time period with and
      without n-CPAP-therapy. In both groups with only one disease a typical pattern of
      the SaO2-values during sleep could be demonstrated. The patients with overlap
      syndrome (SAS + COB) showed a superposition of both single disease SaO2-time
      courses even with much lower initial SaO2-values. During n-CPAP-therapy in all
      groups a reduction of the variations of SaO2 induced by sleep pattern and
      circadian rhythm are evident.

PMID- 8153098
TI  - [Use of acoustic rhinometry for determining segmental airway geometry with nasal
      positive or negative pressure].
AB  - The investigations show an application of nasal acoustic rhinometry for
      determination of segmental naso- and oropharyngeal airway cross-section during
      negative or positive pressure breathing. The investigations show in 16 patients
      with obstructive sleep apnoea (AI = 21.5), that negative pressure produces a
      segmentally different reduction of naso-oropharyngeal cross-section which is
      weakly correlated to the Broca index. But the amount of cross-sectional reduction
      is highly significantly correlated to the apnoea index (r = 0.64). The functional
      relationship between pressure load of the airways during wakefulness and the
      severe nature of the disease reveals the possibility of diagnostic use.

PMID- 8153099
TI  - [Unexplained confusion in the aged as a sequela of central sleep apnea syndrome-
      a case report].
AB  - Central sleep apnoea syndromes (cSAS) represent a heterogeneous group of sleep
      related disorders of breathing during sleep. cSAS may develop in the course of
      neurological syndromes or congestive heart failure. Frequency increases with age.
      A case of a 89-year old man is reported who was sent to hospital because of a
      state of confusion. He fell asleep all day with periods of restlessness during
      night. Sleep-related apnoeas could already be observed during daytime.
      Cardiopulmonary daytime diagnostics did not reveal any abnormal findings.
      Polysomnographic measurements, however, showed an apnoea-hypopnoea index of 37.8
      apnoeas/hypopnoeas per hour with predominantly central apnoeas. Pernasal
      application of 1 litre of oxygen per minute during sleep normalised breathing
      patterns, daytime sleepiness, and the nighttime states of confusion stopped.
      Consequently, sleep-related disorders of breathing have to be considered in the
      differential diagnostics of unclear states of confusion in old age. In these
      cases polysomnography is indicated even in geriatric patients.

PMID- 8153100
TI  - [Long-term theophylline therapy in sleep apnea--follow-up over a period of 12
      months].
AB  - Among all the sleep-related respiratory disorders, sleep apnoea is clinically the
      most important one because of its high incidence and potential cardiovascular
      sequelae. Treatment depends upon the risk profile of the individual patient; in
      severe cases or in risk patients nasal continuous superpressure ventilation is
      employed, whereas in milder cases theophylline has been successfully used
      alongside general measures. 103 patients were followed up during treatment on an
      outpatient basis for 2 to maximum 12 months. Initially a significant reduction of
      the apnoea index by a 50% average was achieved. This therapeutical effect
      remained largely constant with a slight average deterioration at the end of the
      observation period, whereas the subjective feeling tone also improved in most
      patients. The treatment course was prematurely discontinued in 34 patients. Good
      to very good success was achieved in a total of 43 patients, whereas 26 patients
      were non-responders either initially or as the treatment proceeded. Even though
      theophylline treatment is now well-tried in mild forms of sleep apnoea,
      predictors for its use in certain groups of patients must be determined before
      treatment is initiated.

PMID- 8153101
TI  - [Sleep apnea screening in a pulmonary-internal medicine rural practice in
      Mecklenburg-Vorpommern].
AB  - In a screening study of a total of 230 patients covered on the occasion of an x
      ray mass screening (Group A: 157 patients) or within the framework of a
      pulmonology-cardiology-orientated medical consulting-room practice (Group B: 73
      patients), 178 patients said "snoring" was their major symptom, whereas 35
      patients considered "apnoea" to be the main complaint. Looking at both groups
      more closely and with greater differentiation we find in Group B a high incidence
      of the characteristic symptoms "snoring" and "apnoea" and a score of more than
      +2, compared with Group A, concomitant with a high coincidence of a positive
      finding in the MESAM study (Group A: ration 55.5:1, Group B: ratio 4.3:1). 18
      patients were found to be suffering from sleep apnoea syndrome. Due to limited
      facilities we have so far been able to adjust only two of these patients to
      CPAP/BiPAP in the sleep laboratory of the Hospital for Pulmonological Diseases in
      Schwerin. We conclude that it seems problematic to conduct mass screening on a
      broad basis of the population (another argument being the cost/benefit ratio),
      whereas it appears to be more effective to conduct an on-target search for sleep
      apnoea syndrome (SAS) in high-risk groups. A prerequisite for appropriate
      coverage and treatment of sleep apnoea patients is to provide patients with on
      target and wide-scope information on the disease pattern; furthermore, both
      doctors and the population must be provided with examination facilities also on
      an outpatient basis.

PMID- 8153102
TI  - [Theophylline in therapy of obstructive sleep apnea?].
AB  - We examined the effect of 375 mg theophylline at night in 95 patients (14 women,
      81 men) with obstructive sleep apnoea. The apnoea-hypopnoea index decreased
      significantly from 20.9 +/- 17.2 to 13.5 +/- 15.8/hour, the nadir of oxygen
      saturation increased from 80.6 +/- 8.5 to 82.4 +/- 8%. A survey of the longterm
      effects of theophylline in 16 initially responding patients revealed after 31-922
      (190 +/- 217) days therapy no statistically significant change of the apnoea
      hypopnoea index; however, the nadir of oxygen saturation was lower compared to
      the beginning of the therapy (83.8 +/- > 79.3 +/- 7.6%). We believe that
      theophylline is useful in single cases of patients with obstructive sleep apnoea,
      but is necessary to reconfirm the positive effect.

PMID- 8153103
TI  - [Obstructive sleep apnea syndrome caused by craniofacial abnormalities].
AB  - Patients with obstructive sleep apnoea syndrome frequently present distinct
      changes in the craniofacial skeleton that result in a structural narrowing of the
      pharynx and promote pharyngeal collapse during sleep. The evaluation of the
      clinical data of patients with and without craniofacial dysmorphia reveals that
      mean age, mean Broca index and the number of additional diseases is decreased in
      patients with craniofacial dysmorphia. Young patients or patients with normal
      weight and OSAS usually present such skeletal changes. The number of sleep
      related breathing disorders and the extent of nocturnal desaturation are also
      decreased in the group of patients with dysmorphia. The structure of sleep is
      similarly disturbed in both groups. In most cases patients with severe
      obstructive sleep apnoea have normal cephalometric data.

PMID- 8153104
TI  - [Comparative computerized tomography cephalometric and pharyngometric studies of
      patients with severe and mild sleep apnea, and in a control group].
AB  - 116 males were examined. Of these, 52 belonged to a control group, whereas 40 had
      severe obstructive sleep apnoea (apnoea index > 20 + clinical symptoms) and 24
      mild obstructive sleep apnoea (apnoea index 5-20 + clinical symptoms) (in the
      following, OSA signifies obstructive sleep apnoea). Cephalometry and planimetric
      examinations of the pharynx were performed in recumbent position with the head in
      neutral position and with shallow respiration. The narrowest passage of the
      pharynx was measured; other measured sites were the areas of the nasopharynx,
      oropharynx (at the level of the tip of the palatine uvula) and of the hypopharynx
      (at the level of the base of the tongue). The sum of all the measured cross
      sections was obtained. The cephalogram was evaluated to obtain the length and
      thickness of the soft palate, the distance between the mandible and hyoid bone,
      the posterior airspace (PAS), the nuchal subcutaneous fatty tissue at the level
      of the spine of the second cervical vertebra (also known as axis), the thickness
      of the posterior pharyngeal wall at the level of the second cervical vertebra, or
      axis, and the angles between the sella, nasion and superior maxilla and between
      the sella, nasion and mandible (SNA and SNB, respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8153105
TI  - [Surgical treatment of obstructive sleep apnea syndrome by osteotomy of the
      facial skeleton].
AB  - At the Philipps-University Marburg 14 patients with obstructive sleep apnoea
      syndrome (OSAS) have so far been successfully treated by surgical maxillo
      mandibular advancement. These results clearly indicate that surgical treatment
      and cure of OSAS by maxillo-mandibular osteotomy is possible in case of an
      appropriate indication.

PMID- 8153106
TI  - [Functional anatomy of the upper airway: cephalometric and reflective acoustic
      studies].
AB  - Cephalometric analysis is an effective tool for the evaluation of craniofacial
      and pharyngeal changes in obstructive sleep apnoea. Meanwhile even for pharyngeal
      changes a lot of average values exist, which show significant differences for
      many cephalometric parameters. Approximately 40% of patients with obstructive
      sleep apnoea proved to have a retrognathic, dolichofacial appearance, which seems
      to contribute to obstructive apnoeas by retropositioning of the skeletal fixation
      for the muscles of the floor of the mouth and the tongue. Acoustic rhinometry for
      transnasal cross-sectional measurements of the upper airways is still under
      clinical trial. Whether it is a valuable supplement to cephalometric evaluation
      in the future will be mainly a question of software development.

PMID- 8153107
TI  - [Polysomnographic study before and after uvulopalatopharyngoplasty].
AB  - Polysomnography measurements were performed before and 8 weeks after surgery
      (UPPP). Most of the cases showed a decrease in the number and duration of apnoea
      phases. Oxygen saturation increases.

PMID- 8153108
TI  - [Long-term results with nasal CPAP ventilation therapy in obstructive sleep
      apnea].
AB  - In 410 patients suffering from severe sleep-apnoea syndrome long-term observation
      was done (0.5-4 years). Treatment with CPAP-breathing normalised haemodynamic
      disorders. Only 1 patient discontinued the therapy. In 30% an increase of CPAP
      pressure and in 2% an decrease of the CPAP pressure was necessary.

PMID- 8153109
TI  - [Long-term treatment of sleep apnea with evening administration of oral retard
      theophylline].
AB  - In 776 patients suffering from sleep apnoea long-term treatment with sustained
      release theophylline was investigated. Responders show a significant reduction of
      apnoea phases. Using an individual theophylline dosage with morning theophylline
      concentrations between 5 and 8 micrograms/ml, only few side effects occurred.
      Positive effects on cardiopulmonary capacity were seen.

PMID- 8153110
TI  - [Effect of nasal positive pressure ventilation in patients with dilated
      cardiomyopathy (NYHA III-IV)].
AB  - 5 patients suffering from dilatative cardiomyopathy (NYHA III-IV) were
      investigated by polysomnography, haemodynamics and CPAP-BIPAP-breathing. In 4
      patients IPAP-breathing with 6 cm H2O resulted in better haemodynamics.

PMID- 8153111
TI  - [Long-term follow-up of patients with central apnea].
AB  - This is a report on 297 patient with central asphycia. The patients were divided
      into three groups according to the blood gases. 21 patients were in group three.
      16 patients died due to right heart failure. In group one and two no patients
      died. In group one spontaneous remissions were seen.

PMID- 8153112
TI  - [CT and MRI in pneumology].

PMID- 8153113
TI  - [Increasing physical endurance with salmeterol].
AB  - 10 patients with mild to moderate chronic obstructive pulmonary disease were
      assessed by lung function tests at rest and spiroergometry before and 1 resp. 7
      hours after inhalation of 50 micrograms salmeterol. The parameters changed as
      follows: Forced exspiratory volume in 1 second: +16% +/- 6% after 1 resp. +13% +/
      5% after 7 hours; airway resistance: -43% +/- 11% resp. -43 +/- 9%. Work
      capacity at the anaerobic threshold (AT): +44% +/- 17% resp. +37% +/- 16%, oxygen
      consumption at the AT (VO2AT): +53% +/- 18% resp. +54 +/- 23%, ventilation at the
      AT (VEAT): +31% +/- 11% resp. 30% +/- 7%. Maximum work capacity: +14 +/- 5% resp.
      +22 +/- 7%, maximum oxygen consumption (VO2max) +58 +/- 24% resp. 64 +/- 22%,
      maximum ventilation (VEmax) +33 +/- 10% resp. + 46 +/- 11%. In conclusion,
      salmeterol leads to a long lasting improvement of exercise capacity. This is
      related to the improvement of the ventilation caused by salmeterol. Significant
      changes of heart rate or blood pressure were not observed.

PMID- 8153114
TI  - [The value of studies of pulmonary gas exchange during exercise for evaluation of
      reduced arterial oxygenation at rest in asymptomatic long-term smokers].
AB  - The aim of this study was to elucidate extent and nature of an impairment of gas
      exchange after long time cigarette-smoking. Pulmonary gas exchange at rest as
      well as during steady state exercise and conventional lung function tests (LFTs)
      were studied in 32 clinically healthy, asymptomatic severe cigarette-smokers (S;
      48.1 +/- 15.7 pack-years) and 32 healthy lifetime nonsmokers (N) between 40 and
      60 years of age, respectively, individually matched for age, body height, body
      weight and gender. Pulmonary function tests of all subjects were within the
      limits of normal values. Except for a slight reduction of MEF25 in S (p < 0.05)
      and a slight increase of FRC (p < 0.05), the groups did not differ with respect
      to LFTs. At rest, however, S had markedly lower values for PaO2, TLO2, DCO and
      KCO, and higher values for AaDO2 and QVA/Qt. Resting measurements for VD/VE and
      PaCO2 did not differ between N and S. During ergometry PaO2 and TLO2 increased
      respectively; AaDO2 and QVA/Qt fell concomitantly with VD/VE and PaCO2. On
      termination of exercise no significant difference between N and S for the above
      variables could be discerned any longer. Our findings confirm that even in
      clinically healthy asymptomatic cigarette-smokers a distinct impairment of gas
      exchange is present. Their improvement during physical exercise primarily
      indicates the presence of reversible ventilation-perfusion mismatching and
      excludes relevant morphologic changes in the lung in these cases.

PMID- 8153115
TI  - Epidemiology of smoking in Europe.

PMID- 8153116
TI  - [The Mycobacteria Working Group: Investigation of resistance of tuberculosis
      bacteria in Germany 1991 and 1992].
AB  - A tuberculosis caused by resistant or even multidrug-resistant TB bacilli seems
      to be of increasing importance in some parts of the world. An exact investigation
      of rates of initial and acquired drug resistance of tubercle bacilli for the
      whole state of Germany is--considering the corresponding technical, logistic and
      economic necessities--rather demanding. The "Arbeitskreis Mykobakterien"
      performed therefore, as a first step, an estimation of global resistance rates of
      tubercle bacilli in Germany based on questionnaires sent to TB laboratories
      throughout the country: only the first strain isolated in a patient in 1991 and
      1992 should have been considered. The results are presented in Table 1.

PMID- 8153117
TI  - [Yellow nail syndrome].
AB  - The yellow nail syndrome, first described in 1964 by Samman and White, consists
      of yellowish, dystrophic nails, lymphedema and pleural effusion. We present the
      clinical findings of a 53 years old woman who suffered of this very rare
      syndrome. The literature review reveals the different clinical features which
      were reported to be associated with the yellow nail syndrome. The pathogenesis of
      this autosomal-dominantly inherited syndrome consists of a dysfunction of the
      lymphatic drainage system, but details remain unknown. Up to now a causative
      treatment does not exist but topic tocopherol may improve the aspect of involved
      nails. A new study reports of good effects of oral zinc-application to nails and
      lymphedema.

PMID- 8153118
TI  - Fractionation of Pneumocystis carinii developmental stages by counterflow
      centrifugal elutriation and sequential filtrations.
AB  - Immunomagnetic sorting, sequential filtrations, and counterflow centrifugal
      elutriation were compared for their ability to obtain enriched populations of
      Pneumocystis carinii developmental stages from infected rat-lung homogenates.
      Elutriation combined with sequential filtrations resulted in highly (> 95%)
      enriched populations of P. carinii cysts and trophozoites with excellent
      viability. This approach offers advantages over previously described methods of
      obtaining enriched P. carinii cell populations and should have important
      applications to research on this organism.

PMID- 8153119
TI  - Inhibitory activity of saccharomyces yeasts on the adhesion of Entamoeba
      histolytica trophozoites to human erythrocytes in vitro.
AB  - Adhesion to target cells represents the first step in infection by Entamoeba
      histolytica. Binding of axenic amoeba (HMI strain) to human red cells in vitro
      was employed as a model of the adhesion process. The influence of precontact of
      trophozoites with suspensions of live Saccharomyces boulardii yeasts, their
      fractions (membranes and yeast-content supernatant before and after filtration to
      eliminate the membrane) or yeast culture medium before and after fermentation was
      investigated. N-Acetylgalactosamine (GalNAC) was employed as the reference
      inhibitory sugar. The percentage of amoebae bearing red cells after pretreatment
      of amoebae with the various suspensions and derivates was determined. Adhesion
      was also evaluated by scanning electron microscopy (SEM). Pretreatment of amoebae
      with the live yeast suspension led to a significant reduction in the percentage
      of adhesion [32% vs 70% in the phosphate-buffered saline (PBS) control]. Reduced
      adhesion was also observed with the filtered and unfiltered supernatant of the
      yeast suspension homogenate [32% and 34%, respectively, vs 69% in the PBS
      control], yeast culture medium at the end of fermentation [49% vs 76% in the PBS
      control] and GalNAC [32% vs 72% in the PBS control]. SEM showed a decrease in the
      number of amoebae bearing red cells and a reduction in the number of red cells
      adhering to amoebae. We conclude that substances produced by the yeasts compete
      with red cells for adhesion sites on amoebae.

PMID- 8153120
TI  - Demonstration of heat-shock protein 70 in the sporozoite stage of malaria
      parasites.
AB  - Three monoclonal antibodies generated by immunization of mice with Plasmodium
      berghei-infected red blood cells were found to react with the 75-kDa heat-shock
      protein (HSP70) present in liver stages and erythrocytic forms of the parasites.
      These antibodies were shown to react with a recombinant protein encoding the
      carboxyl terminal half of PfHSP70 (aa 365-681). Differently from earlier results,
      we clearly demonstrated that HSP70 was also expressed in the sporozoite stage,
      using these monoclonal antibodies in an immunofluorescence and Western immunoblot
      assay. These monoclonal antibodies react not only with sporozoites of P. berghei,
      the parasites originally used for the immunization, but also with sporozoites of
      several other rodent and human plasmodial species. Passive transfer of these
      monoclonal antibodies into naive mice, simultaneously injected with sporozoites,
      failed to neutralize the infectivity of P. berghei sporozoites and to inhibit the
      development of liver stages of P. yoelii.

PMID- 8153122
TI  - Description of Cosmocerca longispicula sp. nov. (Nematoda: Cosmocercidae), a
      parasite of a dendrobatid frog from Martinique, French Antilles.
AB  - Cosmocerca longispicula sp. nov. (Nematoda: Cosmocercidae), a new cosmocercid
      nematode discovered in the intestine of a new dendrobatid frog from Martinique,
      French Antilles, is described and illustrated. It is unique in possessing
      unusually long, well-sclerotized spicules (length, 0.294-0.300 mm; length ratio
      of gubernaculum and spicules, 1: 2.1-2.2), a feature that necessitates emendation
      of the definition for the genus Cosmocerca. C. longispicula is the first known
      species of Cosmocerca from the Caribbean region. A new name, C. paraguayensis
      nom. nov., is proposed for C. uruguayensis Moravec and Barus, 1990, a homonym to
      C. uruguayensis Lent and Freitas, 1948.

PMID- 8153121
TI  - Reproductive failure in mice chronically infected with Toxoplasma gondii.
AB  - Nya: NYLAR female mice infected with Toxoplasma gondii for 1 and 2 months were
      cohabited with normal males for 1 week, then sequestered individually to monitor
      their reproductive performance. Mice bred 1 month postinfection (p.i.) exhibited
      reproductive failure, with 1 of 16 females delivering 2 sickly pups; in others,
      interruption of pregnancy and fetal wastage occurred. Mice infected for 2 months
      were uniformly infertile. Vaginal lavage showed cessation of estrus cycling and
      constant diestrus cytology at as early as 1 month p.i. Histologic examination of
      the ovaries revealed impaired folliculogenesis and few corpora lutea, if any.
      Uterine atrophy was marked. Coronal sections of the cerebrum disclosed widespread
      vasculitis, focal disruptions of the ependymal cell layer lining the lateral and
      third ventricles, and periventricular edema. We suggest that the reproductive
      failure of the infected mice is due to an acquired hypogonadotropic hypogonadism
      secondary to hypothalamic dysfunction.

PMID- 8153124
TI  - Light and scanning electron microscopic observations of the eggs, daughter
      rediae, cercariae, and encysted metacercariae of Echinostoma trivolvis and E.
      caproni.
AB  - Light microscopy (LM) and scanning electron microscopy (SEM) were used to
      determine interspecific differences between various larval stages of 2 allopatric
      species of 37-collar-spined echinostomes, Echinostoma caproni and E. trivolvis.
      The abopercular and embryo diameters of the eggs of E. trivolvis were
      significantly different from those of E. caproni. The abopercular knobs of E.
      caproni and E. trivolvis have shallow and deep infoldings in the eggshells,
      respectively. Interspecific differences were noted in the tegument, tegumentary
      papillae, and spherical bodies around the mouth and in the papilliform process of
      the two rediae. The cercaria of E. caproni has one ventral tail fin-fold, whereas
      that of E. trivolvis has two; both species have two dorsal tail fin-folds. The
      outer metacercarial cyst diameter of E. caproni was significantly greater than
      that of E. trivolvis. E. caproni has a smoother outer cyst wall than does E.
      trivolvis.

PMID- 8153123
TI  - Cloning and characterisation of a repetitive DNA sequence from Theileria mutans:
      application as a species-specific probe.
AB  - Repetitive DNA sequences were isolated from a Theileria mutans genomic library by
      screening with T. mutans total DNA. DNA sequence analysis demonstrated that a
      section of one of the clones contained a complex series of overlapping perfect
      repeats ranging between 99 and 20 bp in size. The T. mutans repetitive sequence
      did not contain large open reading frames (ORFs), unlike T. parva Tpr repetitive
      DNA sequences. When used as a hybridisation probe the repetitive sequence
      revealed restriction-fragment-length polymorphisms (RFLPs) between the EcoRI
      digested DNAs of two T. mutans stocks. The T. mutans repetitive probe gave a
      signal with 1 ng of purified T. mutans piroplasm DNA and detected T. mutans
      sequences in whole-blood DNA isolated from an experimentally infected animal when
      the piroplasm parasitaemia was equal to or above 0.4%. Oligonucleotide primers
      derived from the repetitive sequence allowed more sensitive detection of T.
      mutans DNA by polymerase chain reaction (PCR) amplification. Using the PCR, T.
      mutans DNA was amplified from an experimentally infected animal with a
      parasitaemia of < 0.1%.

PMID- 8153125
TI  - Eimeria media: selection and characterization of a precocious line.
AB  - A precocious line of Eimeria media was obtained by selection for early
      development of oocysts in rabbits. The prepatent period was reduced from 108 to
      72 h. The precocious line was less pathogenic than the original strain, and its
      multiplication rate was lower. Rabbits given oocytes of the precocious line were
      totally immune to challenge with the original strain as assessed by change in
      weight gain but were partially protected as assessed by oocyst output. Selection
      for precocious development was accompanied by morphological changes in the
      sporulated oocytes; each sporocyst contained only one large refractile body
      instead of the two smaller bodies seen in the original strain.

PMID- 8153126
TI  - Freeze-fracture characterization of the cuticle of adult and dauer forms of
      Caenorhabditis elegans.
AB  - At the ultrastructural level, a trilaminate structure, designated as the
      epicuticle, is always present on the outermost surface of the nematode
      Caenorhabditis elegans. The freeze-fracture technique revealed the existence of
      two fracture faces: an inner face that showed homogeneously distributed particles
      and an outer fracture face that was almost completely smooth in adult nematodes
      but appeared delicately granular in the dauer forms.

PMID- 8153127
TI  - Kinetics study and characterisation of target excreted/secreted antigens of
      immunoglobulin G, M, A and E antibodies from mice infected with different strains
      of Toxoplasma gondii.
AB  - A kinetics study and characterisation of target excreted/secreted antigens of
      immunoglobulin (Ig) G, M, A and E antibodies were realised by Western blotting
      with immune sera of mice inoculated with three strains of Toxoplasma gondii: RH,
      C56 and S3. IgG antibodies of the immune sera recognised the major proteins of
      the three excreted/secreted antigen preparations with molecular masses of 30, 45,
      63 and 77 kDa. IgM antibodies recognised proteins revealed by IgG antibodies but
      with variable intensities; some proteins were revealed during a short period. IgA
      antibodies did not recognise the 35-kDa antigen or the antigens inferior to 28
      kDa. The RH excreted/secreted antigens were revealed with the highest intensity.
      The IgE antibodies were briefly detected in trace amounts during period from the
      20th to the 35th day. The RH strain with its excreted/secreted antigens had the
      best antigenicity and is a good model for immunoprotection studies.

PMID- 8153128
TI  - Partial characterization and kinetics of expression of Sm15, a Schistosoma
      mansoni tegumental antigen.
AB  - Differential antibody screening of an adult Schistosoma mansoni cDNA expression
      library constructed in lambda gt11 identified a partial cDNA clone, A70. This
      cDNA encodes a fusion protein recognized by antibodies raised against highly
      irradiated schistosomula and adult worm tegumental membranes but not by anti-egg
      antibodies. Anti-tegumental membrane antisera affinity-purified on the A70 cDNA
      fusion protein were used for Western blotting analysis and indirect
      immunofluorescence, resulting in the identification of a 15-kDa protein (Sm15) in
      the tegument of adult worms. This is one of the principal tegumental antigens
      recognized by antibodies from mice protectively vaccinated with adult worm
      tegumental membranes. Sm15 is much smaller than the protein encoded by its gene,
      suggesting that it results from a highly processed precursor. It was found that
      Sm15 behaves as an integral membrane protein upon partitioning in Triton X-114
      and that it is present in worms of 2 weeks or older but not in schistosomula or
      miracidia. The affinity-purified antibodies also revealed the presence of a 23
      kDa antigen in whole-worm homogenates that is apparently coexpressed with Sm15.
      The 23-kDa antigen was not found associated with membranes and is probably a
      soluble protein. A further series of Western blots were undertaken using
      antibodies affinity-purified from serum raised against schistosomula. In this
      case, the 23- and 15-kDa products were not recognized, but rather soluble
      proteins ranging from 45- to 150-kDa were detected in almost all larval stages
      investigated. The results suggest that the precursor is differentially processed
      during maturation.

PMID- 8153129
TI  - Alterations of uninfected red blood cells in malaria.
AB  - Red blood cell (RBC) negative charges and resistance to linoleic acid (LNA)
      induced lysis were studied in Plasmodium yoelii-infected mice and in malaria (P.
      falciparum)-affected individuals. RBCs from mice infected with P. yoelii showed a
      progressive decrease in the net surface negative charges at 24 h after infection,
      reaching a minimal value on day 3, followed by a second phase that was
      characterised by a recovery to normal levels on day 6. Resistance to linoleic
      acid follows similar kinetics. These alterations preceded the appearance of
      parasites in the peripheral blood. A similar increase in LNA-induced lysis was
      observed in RBCs from malaria-affected individuals. These early membrane
      alterations of uninfected RBCs could be responsible for spreading of infection
      and RBC lysis during infection.

PMID- 8153130
TI  - Effects of estradiol on worm burden and peripheral leukocytes in Parastrongylus
      malaysiensis-infected rats.
AB  - Gonadectomized male laboratory rats were given 0.06 mg/kg estradiol benzoate
      daily for 14 days before being inoculated with 50 third-stage larvae of
      Parastrongylus malaysiensis. Hormone treatment was continued until the rats were
      killed. The numbers of larvae in the brain and of adult worms in the pulmonary
      area of the rats were determined every 7 days after the inoculation. It was found
      that the rats treated daily with estradiol benzoate had significantly and
      consistently higher numbers of larvae and adult worms as compared with the
      controls. The number of total leukocytes increased significantly after the rats
      were infected. The results show that estradiol-treated rats become susceptible to
      P. malaysiensis infection, which may indicate that the immunosuppressive effects
      of testosterone observed in earlier studies may partly be caused by estradiol
      that was peripherally aromatized from testosterone.

PMID- 8153131
TI  - Atrial natriuretic factor in experimental acute Chagas' disease.

PMID- 8153132
TI  - Deer keds (Lipoptena cervi) in the accompanying equipment of the late Neolithic
      human mummy from the Similaun, South Tyrol.

PMID- 8153133
TI  - Serum-free cultivation of several Plasmodium falciparum strains.
AB  - Plasmodium falciparum strains from different malaria-endemic regions were grown
      in continuous culture without human serum. The medium was complemented with
      Nutridoma-SR instead of serum. All parasite strains developed well in serum-free
      medium. Two strains were thawed without serum and showed good multiplication in
      subsequent continuous culture.

PMID- 8153134
TI  - The influence of thyroxine and propyl thiouracil on Parastrongylus malaysiensis
      infection in rats.
AB  - Daily intramuscular injection with thyroxine (T4) at a dose of 2.5 micrograms/100
      g body weight decreased the larvae and adult worm burden of Parastrongylus
      malaysiensis in the brain and pulmonary arteries of male Sprague-Dawley albino
      rats. In contrast, rats treated with propyl thiouracil (PTU), an antithyroid
      drug, at a dose of 3.75 mg/100 g body weight retained greater numbers of larvae
      and adult worms. The results may reflect the contrasting immunomodulatory effects
      of T4 and PTU that influence the susceptibility of the host.

PMID- 8153135
TI  - Is mate choice copying or aggregation responsible for skewed distributions of
      females on leks?
AB  - In several lek-breeding populations of birds and mammals, females arriving on
      leks tend to join males that already have females in their territories. This
      might occur either because females have an evolved preference for mating with
      males that are attractive to other females, or because they join groups of other
      females to obtain greater safety from predation or dangerous harassment by males.
      We have previously used controlled experiments to show that oestrous fallow deer
      females join males with established harems because they are attracted to female
      groups rather than to the males themselves. Here we demonstrate that the
      preference for males with females over males without females is specific to
      oestrous females and weak or absent in anoestrous ones, and that it is not
      associated with a preference for mating with males that have previously been seen
      to mate with other females. Furthermore, oestrous females given the choice
      between males that do not already have females with them show no significant
      preference for antlered over deantlered males or for older males over younger
      ones. We conclude that female attraction to other females on the lek is likely to
      be an adaptation to avoiding harassment in mixed-sex herds. In this situation, a
      male's ability to maintain the cohesion of his harem may be the principal cause
      of variation in mating success between males.

PMID- 8153136
TI  - Sexual selection and genital anatomy of male primates.
AB  - Correlations between mating system and various aspects of genital anatomy suggest
      a strong influence of sexual selection on genital morphology. We test the
      generality of the influence by examining whether primate taxa in which there
      might be enhanced sexual selection (those with multi-male mating systems)
      possess, as expected, relatively more spinous penises than do taxa with other
      mating systems. As most prosimians, but few anthropoids (monkeys and apes),
      possess penile spines, and because the predominant mating systems of the two taxa
      differ, taxonomic constraints are taken into account. Sexual selection apparently
      does not act on penile spines in the same manner as on other aspects of genital
      anatomy: spinosity is not greatest in multi-male taxa of either prosimians or
      anthropoids. In some taxa, spines might stimulate reproductive readiness and
      synchrony in situations in which the sexes live apart and do not have other means
      of communicating reproductive state (dispersed social systems and 'stolen' extra
      pair copulations), but problems exist with the hypothesis, as they do with the
      idea that spines are involved with scent marking. It seems that either penile
      spines have several functions, or penile spinosity in primates, and other orders,
      remains to be explained.

PMID- 8153137
TI  - Optical measurements of activity-dependent membrane recycling in motor nerve
      terminals of mammalian skeletal muscle.
AB  - Motor nerve terminals in a variety of rat and mouse skeletal muscles were stained
      in an activity-dependent fashion using the styryl dyes FM1-43 or FM2-10. Low
      light video microscopy and digital image processing techniques were used to
      evaluate destaining of the preparations during application of depolarizing
      stimuli. Best results were obtained with the mouse triangularis sterni muscle.
      Quantitative analysis of the destaining of dye-loaded terminals supports the
      suggestion that FM1-43 stains a recycling membrane compartment, most probably
      synaptic vesicles. However, the pattern of staining and destaining were not the
      same as those reported previously for frog neuromuscular junctions. The pattern
      of nerve terminal staining was less punctate and the rate and amount of activity
      dependent destaining were less than in frog muscle. Part of the explanation may
      be a more acute susceptibility of mammalian terminals to phototoxicity.

PMID- 8153138
TI  - pH-gated dopaminergic modulation of horizontal cell gap junctions in mammalian
      retina.
AB  - Horizontal cells mediate lateral inhibition in the outer retina, and this process
      is dependent on electrical coupling through gap junctions, giving rise to
      receptive fields that are much wider than the dendritic fields. This study on
      rabbit retina shows that the permeability of the gap junctions between A-type
      horizontal cells, as assessed by Lucifer yellow dye coupling, is modulated by
      dopamine through a D1 receptor linked to adenylate cyclase. Both exogenously
      applied dopamine and endogenously released dopamine uncoupled the horizontal
      cells, but the effect was pH-gated whereby it occurred only at an extracellular
      pH 7.2 +/- 0.05. The horizontal cells also uncoupled in acidic media (pH 7.0 or
      below) in the absence of dopamine. Our results show that horizontal cell coupling
      in the mammalian retina is regulated by both dopamine and pH. Given that the pH
      in the outer retina varies with the metabolic activity of the photoreceptors,
      these results suggest that ambient light conditions could gate the activity of
      neurotransmitters through pH-sensitive mechanisms.

PMID- 8153139
TI  - Descending serotonergic spinal projections and modulation of locomotor
      rhythmicity in Rana temporaria embryos.
AB  - The neuroanatomy of descending spinal projections from serotonergic raphe
      interneurons in embryos of the amphibian, Rana temporaria, has been examined
      around the time of hatching by using immunocytochemical techniques. The results
      illustrate that at this early stage in development the ventrolateral spinal cord
      is richly innervated by 5HT immunoreactive (5HTi) raphe spinal axons and
      associated growth cones. Other regions are devoid of processes. In conjunction,
      the effects of bath applied 5-hydroxytryptamine (5HT, serotonin) and its
      metabolic precursor, 5-hydroxytryptophan (5HTP) on locomotor activity, was also
      investigated by monitoring ventral root activity during fictive swimming in
      immobilized animals. Fictive swimming activity is similarly modulated by both
      exogenously applied 5HT and enhanced endogenous release of 5HT (using 5HTP).
      These agents increase the duration and intensity of ventral root burst, decrease
      cycle frequency, lengthen rostrocaudal phase delays and reduce swimming episode
      duration. We conclude that by the time of hatching in Rana temporaria a
      functional endogenous serotonergic system is established in the spinal cord which
      modulates the output of the central pattern generator for swimming. We compare
      and contrast these results with homologous descending pathways in other
      vertebrates, especially in a related amphibian Xenopus laevis at equivalent
      stages in development.

PMID- 8153140
TI  - Superinfection and the evolution of parasite virulence.
AB  - Earlier ideas that parasites evolve toward becoming harmless to their hosts have,
      in recent years, given way to more analytic studies, focused on the 'basic
      reproductive rate', R0, of individual parasites. In general, the biology of the
      parasite life cycle will lead to constraining relations between virulence
      (parasite-associated host death or reduction in fertility) and transmissibility:
      the maximum R0 may then be attained by virulence being high, or low, or at some
      intermediate level, depending on the details of the constraining relations. Such
      studies have not generally included superinfection (where an already-infected
      host is infected by another parasite). Here we propose a general, but simple,
      model of superinfection, which is amenable to analytical treatment. In such
      models selection does not simply act to maximize R0; superinfection leads to
      selection for higher levels of virulence, highly polymorphic parasite populations
      and very complicated dynamics. We calculate the equilibrium distribution of
      parasite strains and the maximum level of virulence that can be maintained by
      superinfection. We also note the equivalence between our 'superinfection model'
      and recent approaches to the study of the meta-population dynamics of multi
      species interactions.

PMID- 8153141
TI  - Aztreonam decreases hepatic microsomal cytochrome P450 in cynomolgus monkeys.
AB  - We examined the effect of successive administrations of aztreonam, which is used
      clinically as an antibiotic, on the mixed function oxidase system in non-human
      primates. Treatment of cynomolgus monkeys with aztreonam at doses of between 40
      and 300 mg/kg for 4 weeks resulted in a significant decrease in the content of
      hepatic microsomal P450. On the other hand, no significant change was observed in
      hepatic cytochrome b5 content and NADPH-cytochrome c (P450) reductase activity
      following treatment with aztreonam. The activity of testosterone 6 beta
      hydroxylase, but not 2 beta- and 16 alpha-hydroxylases in hepatic microsomes, was
      decreased following the treatment of cynomolgus monkeys with aztreonam. The
      content of P450 CMLc, which is classified into the 3A subfamily, was also
      decreased by aztreonam treatment although the content of P450 CMLb, which is a 2A
      enzyme in cynomolgus monkeys, was unchanged. From these results, we concluded
      that aztreonam decreased P450 CMLc in hepatic microsomes of cynomolgus monkeys.

PMID- 8153142
TI  - Endotoxin-mediated changes in plasma endothelin concentrations, renal endothelin
      receptor and renal function.
AB  - The purpose of these studies was to examine the changes in renal endothelin (ET)
      receptor, renal function and plasma ET (ET-1) concentration in male Sprague
      Dawley rats injected with nonlethal doses of Escherichia coli endotoxin (LPS).
      Prior to the injection of LPS, kidney ET receptor density was 59 +/- 5 fmol/mg
      protein (n = 20). At 24 h after the injection of 1 or 3 mg/kg LPS, [125I]ET-1
      binding to kidney membranes was increased by 70% in both LPS groups (p < 0.001).
      Scatchard analysis of the saturation binding experiments confirmed that the
      increase in [125I]ET-1 binding was due to an increase in receptor density with no
      change in affinity (202 pmol/l at baseline and 168 pmol/l and 246 pmol/l at 24 h
      after the injection of 1 and 3 mg/kg LPS, respectively). At 7 days after the
      injection of LPS, kidney ET-1 receptor density was still increased by 30 +/- 5%
      and 58 +/- 16%, respectively (p < 0.05, compared to the baseline value). Baseline
      values for Na+ and K+ excretion were approximately 115 muEq/h and 214 +/- mu/Eq/h
      respectively, and were decreased with LPS. Maximal decreases in Na+ and K+
      excretion occurred at 48 h (-85%) and 30 h (-82%), respectively, following the
      injection of 3 mg/kg LPS and returned to baseline levels in 7 days. Following the
      injection of 3 mg/kg LPS, plasma immunoreactive ET-1, as measured by
      radioimmunoassay, increased in a time-dependent manner: the maximal increase of
      60% occurred within 1 h after the injection of LPS (p < 0.05), and thereafter
      returned to baseline levels. Kidney tissue levels of ET-1 increased from baseline
      values of 2.6 fmol/mg protein to a peak of 4.6 fmol/mg protein 1 h after the
      injection of LPS. Tissue ET-1 levels were still significantly elevated at 6 h but
      not 24 h after LPS injection. These studies suggest that ET-1, either by
      increases in plasma concentration and/or altered receptor density, may be
      involved in the LPS-induced impairment of renal function.

PMID- 8153143
TI  - Protective effects of IRFI-016, a new antioxidant agent, in myocardial damage,
      following coronary artery occlusion and reperfusion in the rat.
AB  - The new free radical scavenger IRFI-016 [2(2,3-dihydro-5-acetoxy 4,6,7-trimethyl
      benzofuranyl) acetic acid] was assessed in a rat model of myocardial injury
      induced by 1 h of left coronary artery occlusion followed by 30 min of
      reperfusion. Myocardial ischaemia plus reperfusion (MI/R) produced severe cardiac
      necrosis, neutrophil infiltration in the jeopardized tissue, increased serum
      creatine kinase (CK) and ST segment of the electrocardiogram (ECG), lowered the
      pressure rate index (PRI), increased serum levels of tumour necrosis factor (TNF
      alpha) and caused a decrease in the survival rate. Administration of IRFI-016
      (100 and 200 mg/kg i.p.) 30 min before occlusion resulted in a significant
      protective effect in post-ischaemic reperfusion. Compared with untreated rats,
      IRFI-016, in particular the dose of 200 mg/kg, caused a reduction of the necrotic
      zone whether the necrotic area was expressed as a percentage of the area at risk
      (55 +/- 4% in the MI/R vehicle group and 24 +/- 2.5% in the MI/R treated group; p
      < 0.001) or as a percentage of the total left ventricle (23 +/- 3.4% in the MI/R
      vehicle group and 8 +/- 2.1% in the MI/R treated group; p < 0.005), reduced the
      myeloperoxidase activity, an index of neutrophil infiltration in the necrotic
      area (from 4.8 +/- 0.8 to 1.6 +/- 0.4 U/g tissue; p < 0.005), reduced the serum
      levels of TNF-alpha (from 216 +/- 13 to 45 +/- 7 U/ml; p < 0.001), blunted the
      rise of the ST segment of the ECG (from 0.47 +/- 0.13 mV in the vehicle group to
      0.3 +/- 0.18 mV in the treated group; p < 0.001), reduced the loss of CK (from
      220 +/- 15 to 88 +/- 13 IU/ml of blood; p < 0.001) and improved the depressed PRI
      (from 56 +/- 4% to 78 +/- 3% mm Hg/beats/min; p < 0.005). Finally, IRFI-016
      significantly enhanced the survival rate evaluated at the end of the experiment.
      The results strongly indicate that IRFI-016 is a promising drug for cardiac
      ischaemia and reperfusion.

PMID- 8153144
TI  - Diuretic and antihypertensive activity of ZENECA ZM224,832: a novel eukalemic
      diuretic with calcium channel blocking activity.
AB  - ZENECA ZM224,832 is a novel eukalemic diuretic from the aminomethylphenol
      pyrazine series which demonstrated a profile of calcium channel blockers. It
      produced diuretic and saluretic effects in animals but had only minimal
      alterations in kaliuresis after oral administration. In contrast to standard
      diuretics, the plasma K+ concentration was not altered in conscious dogs treated
      for 14 days with ZENECA ZM224,832 and the concurrent plasma renin activity was
      also minimally elevated. The isolated rat aorta evaluation indicated that ZENECA
      ZM224,832, like tiapamil and nifedipine, inhibited vascular smooth muscle tone by
      inhibiting voltage-dependent calcium channels. ZENECA ZM224,832 produced a dose
      dependent decrease of blood pressure in spontaneously hypertensive rats (SHR) in
      which the antihypertensive activity was not noted with HCTZ. In addition, ZENECA
      ZM224,832, similar to diltiazem, produced an acute blood pressure lowering effect
      in nephrectomized SHR which was independent of its diuretic activity. It is
      concluded that ZENECA ZM224,832 is a potent eukalemic diuretic with calcium
      channel blocking properties.

PMID- 8153145
TI  - Phospholipid synthesis in isolated porcine gastric mucous cells.
AB  - Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the major
      phospholipids of the gastric mucosal surface barrier and chiefly originate from
      mucous cells. Among these phospholipids PC with palmitic acid as its hydrophobic
      moieties is believed to protect the gastric mucosa by its hydrophobic properties.
      We investigated the phospholipid synthesis of isolated porcine gastric mucous
      cells in vitro and incubated them in the presence of radiolabelled precursors.
      Incorporation of 3H-choline into PC and of 14C-ethanolamine into PE was linear at
      1, 10, and 100 mumol/l substrate concentration for at least 6 h. Half-maximal
      rate of precursor incorporation was achieved at 21 and 15 mumol/l of choline and
      ethanolamine, respectively. Ethanolamine inhibited PC synthesis and choline
      inhibited PE synthesis. A small amount of radioactivity originating from 14C
      ethanolamine and from the methyl groups of 3H-methionine were incorporated into
      PC. Palmitic acid was incorporated into PC more than PE. Indomethacin did not
      influence the de novo synthesis of PC and PE via the Kennedy pathway, but
      inhibited the incorporation of 3H-methionine into PC. These results indicate that
      in gastric mucous cells PC and PE synthesis de novo depends on the concentrations
      of choline and ethanolamine. The palmitic acid content of PC depends on the
      availability of palmitic acid as a substrate: indomethacin-induced mucosal damage
      is not explained by modulation of phospholipid synthesis de novo.

PMID- 8153146
TI  - Effects of dotarizine on peripheral and pulmonary circulation and cardiac
      dynamics in dogs.
AB  - The cardiovascular effects of dotarizine in 10-min intravenous infusions were
      studied in thiopental-anesthetized dogs. The effects of dotarizine 0.024
      mg/kg/min almost paralleled those of saline controls; 0.079 mg/kg/min dotarizine
      significantly raised the stroke index and ejection fraction, and, at a rate of
      0.25 mg/kg/min, further effects appeared and were dose-dependent. Dotarizine
      produced arterial dilation in both systemic and pulmonary circulation: the total
      peripheral resistance dropped, and femoral artery flow rose; aortic and pulmonary
      artery mean and diastolic pressures declined, and systolic pressures remained
      almost stable. A trend of bradycardia and pulmonary artery pressure reduction
      persisted for 30 min. As compared with the reduced total peripheral resistance,
      aortic pressure fell only moderately because of rising cardiac output due to a
      higher ejection fraction and stroke volume. Cardiac preload tended to decline;
      contractility tended to increase. Cardiac performance remained stable while
      myocardial oxygen consumption tended to fall, as did the pressure-rate product
      and the tension time index. Dotarizine exerted direct cardiovascular effects
      similar to those of the 5-HT2-receptor antagonist ketanserin and, more generally,
      to calcium channel blockers rather than to alpha-adrenoceptor blockers.

PMID- 8153147
TI  - Effects of prostacyclin and beraprost on ciliary motility of rabbit airway
      epithelium.
AB  - The effects of prostacyclin and its stable analog beraprost on ciliary beat
      frequency (CBF) of rabbit tracheal epithelium were studied by a microphoto
      oscillation technique in vitro. Addition of these drugs increased CBF in a dose
      dependent fashion: the maximal increase from the baseline value and the drug
      concentration required to produce a half-maximal effect were 13.3 +/- 2.0% (p <
      0.05) and 1.8 +/- 0.4 x 10(-7) mol/l for prostacyclin and 30.8 +/- 3.4% (p <
      0.001) and 1.6 +/- 0.5 x 10(-7) mol/l for beraprost. These effects were
      accompanied by the increase in intracellular cyclic AMP levels. Thus,
      prostacyclin and beraprost may stimulate ciliary motility and, hence, mucociliary
      transport through the production of cyclic AMP.

PMID- 8153149
TI  - Transient cytoplasmic vacuolization in cultured normal and neoplastic cells
      treated with low molecular weight human serum ultrafiltrate: is out inside?
AB  - Human embryonal fibroblasts (HEF) and epithelial carcinoma cells (HEp-2) were
      exposed to low molecular weight (LMW) fractions (M(R) < 50-kDa) of human serum,
      generated by ultrafiltration. A prominent change in cytoplasmic morphology was
      detected by microscopic analysis of both cell types. Within 1-3 h of incubation
      an extensive vacuolization was induced, which phenotype was maintained for 6-12 h
      in the presence of the LMW filtrate in a cell type dependent manner, followed by
      a spontaneous reconstitution of the original cytoplasmic morphology by 24 h.
      Reversibility occurred by incubation in medium without filtered serum fractions.
      Transmission electron microscopy revealed vesicles without continuous bordering
      membrane or electron dense interna and demonstrated vacuoles in close contact
      with filamentous structures. Taken together the light- and electron microscopic
      characteristics of the observed vacuolization, potential interpretations of our
      results are discussed in the context of general cytoplasmic organization.
      Rearrangement of the cytoplasmic protein-water system as a consequence of an
      inductive effect of serum filtrates is proposed.

PMID- 8153148
TI  - Activities of drug-metabolizing enzymes in the liver of Suncus murinus: possible
      lack of N-acetyltransferase activity in liver cytosol.
AB  - The amounts of several drug-metabolizing enzymes in livers of Suncus murinus
      (suncus) were studied in comparison with rats. The content of cytochrome P450 in
      suncus was less than one third that seen in rats. Activities of glutathione S
      transferase, UDP-glucuronyltransferase and arylhydroxycarbon hydroxylase in
      suncus were less than half those in rats. Activity of flavin-containing
      monooxygenase in suncus was 71% that of rats. Interestingly, N-acetyltransferase
      (NAT) activity in suncus liver cytosols was not detectable: no detectable
      activities were seen with aniline, p-aminobenzoic acid and p-amino-salicylic acid
      as substrates. We propose that suncus is a unique animal possibly lacking NAT in
      liver cytosol.

PMID- 8153150
TI  - Increase in cell responses and protein phosphorylation of neutrophils induced by
      synthetic diacylglycerols.
AB  - Diacylglycerols (DG) induced various stimulation-coupled responses of guinea pig
      peritoneal neutrophils (GPPMN), such as superoxide (O2-.) generation, luminol
      chemiluminescence response (LCL) and membrane depolarization. These activities
      induced by L-alpha-1,2-dioctanoyl glycerol (diC8) are quite similar to those
      induced by phorbol 12-myristate 13-acetate (PMA). The effects of diC8 were much
      stronger than those of L-alpha-1-oleoyl-2-acetylglycerol (OAG) and no effect was
      produced by L-alpha-1,2-dioleoyl glycerol (DO). Concentrations of diC8 and OAG
      for maximal O2-. generation were 1 and 10 microM, respectively. However, rat
      brain Ca(2+)- and phospholipid-dependent protein kinase (PKC) was activated by
      all DGs used, and the concentrations of OAG, DO and diC8 for half maximum
      stimulation were 0.2, 1.0 and 2.0 microM, respectively. Discrepancies between the
      concentrations of DGs required for O2-. release and PKC activation might be due
      to differences in their affinity for and permeability in the membrane. The
      generation of active oxygen and the PKC activity were both sensitive to PKC
      inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7) and
      staurosporine. ID50 of H-7 and staurosporine for the inhibition of diC8-induced
      O2-. release were 150 nM and 10 nM, respectively. By contrast, staurosporine does
      not inhibit diC8 induced membrane depolarization. Phosphorylation of cytoplasmic
      proteins, such as the 47 kDa protein, was increased by DGs and this
      phosphorylation was also inhibited by H-7 or staurosporine. The capacities of
      stimulating the rates of 47 kDa protein phosphorylation were in the order diC8 >
      OAG > DO. These results suggest the involvement of protein phosphorylation in DG
      induced O2-. generation. However, a part of the O2-. generation induced by high
      concentration of DG might have occurred via a PKC-independent pathway.

PMID- 8153151
TI  - Inhibitory effect of alpha-tocopherol on methemoglobin formation by nitric oxide
      in normal and acatalasemic mouse hemolysates.
AB  - The inhibitory effect of alpha-tocopherol on methemoglobin formation in normal
      and acatalasemic mice was studied by exposing their hemolysates to nitric oxide.
      Methemoglobin formation in normal and acatalasemic mouse hemolysates exposed to
      nitric oxide were significantly inhibited by the addition of alpha-tocopherol at
      final concentrations ranging from 1.2 to 5.8 mM. Negative correlations were
      observed between the logarithm of alpha-tocopherol concentration and the
      methemoglobin formation. The formation of methemoglobin in acatalasemic mouse
      hemolysates was greater than that in normal mouse hemolysates with or without
      added alpha-tocopherol. The methemoglobin formation in acatalasemic mice was also
      significantly inhibited by addition of more than 500 units/ml of catalase, and
      the methemoglobin formation in normal and acatalasemic mice was also inhibited
      with sodium diethyldithiocarbamate at a final concentration of 1 M.

PMID- 8153152
TI  - Dual nature of the intracellular cations. Conductance of adsorbed intracellular
      cations in the region of microwave frequencies.
AB  - The majority of intracellular ions was "invisible" by classical conductance
      measurements over the regions of audio and radio frequencies. In the microwave
      region all the cations become "visible" in muscles. A non-invasive method is
      found to determine the cationic content of biological tissues. The better the
      physical condition of the muscle the greater the new parameter, the invisible
      cationic conductivity. 15% of the total cation content is released by thermal
      treatment that was probably associated with negative phosphate or carboxylate
      groups of the lipoid surface of the membrane structure. This K+ fraction in the
      frog muscle has been already discovered by three quite different methods.

PMID- 8153153
TI  - The oxidative deamination of L-aminoethylcysteine sulfoxide and sulfone by snake
      venom L-amino acid oxidase.
AB  - The oxidation of L-aminoethylcysteine (AEC) by L-amino acid oxidase has been
      compared with that of the respective sulfoxide (AEC-SO) and sulfone (AEC-SO2).
      Spectral and HPLC analyses of the incubates reveal the formation of the
      respective cyclic ketimines. While the ketimine coming from AEC is subjected to
      autooxidation yielding the sulfoxide and other products, the ketimines produced
      from AEC-SO and AEC-SO2 are more stable and account for almost the total
      conversion of the substrate in the product. Spectrophotometric and HPLC
      properties of the ketimine produced from AEC-SO are identical to those reported
      earlier for the main product of the autooxidation of AEC ketimine, thus
      confirming its identification. These results could explain the presence of
      chondrine in biological materials as a product of reduction of AEC-SO ketimine.

PMID- 8153154
TI  - Cellular deformability studies in leukemia.
AB  - This study was carried out to investigate the red blood cell and white blood cell
      deformability index in leukemia which is marked by an uncontrolled increase of
      leucocytes in the bone marrow as well in peripheral blood. It was observed that
      leucocytes are less deformable than erythrocytes, and erythrocytes from Chronic
      Myelogenous Leukemia (CML) patients less deformable than normal erythrocytes. The
      deformability indexes for lymphoblasts from acute lymphoblastic leukemia and
      myeloblasts from acute myelogenous leukemia were almost the same and higher than
      that of granulocytes from chronic myelogenous leukemia. These observations led to
      the conclusion that the significant increase in the resistance to the flow of
      blood in vivo in leukemia may be due to the increase in the number of leucocytes
      which are more rigid than erythrocytes.

PMID- 8153155
TI  - A note on the influence of anesthetics on relaxation times in biological systems.

PMID- 8153156
TI  - Tolerance to the anorectic effect of dexfenfluramine in rats: role of serotonin,
      cholecystokinin, and neuropeptide Y.
AB  - Tolerance to the anorectic effect of dexfenfluramine (DFEN) is shown in rats
      treated either chronically with low doses or once with a high dose of the agent.
      Rats given DFEN regimens that result in complete loss of DFEN anorexia showed no
      change in the anorexia caused by peripheral injection of cholecystokinin (CCK).
      The orexigenic effects of metergoline and neuropeptide Y were also unaltered as a
      function of DFEN pretreatment. Both the magnitude and duration of tolerance to a
      test dose of DFEN seemed to depend, in part, upon contingent (situational)
      factors, and were independent of whether brain serotonin (5-HT) measures were
      either unaffected or decreased by the DFEN pretreatment (low and high doses,
      respectively).

PMID- 8153157
TI  - Behavioral and electrocardiographic responses to social stress in male rats.
AB  - Telemetry ECGs were recorded from Wistar male rats during social stress induced
      by exposure to aggressive lactating female rats. Behavioral response to maternal
      attack was evaluated in terms of relative duration of passive submissive (p/s)
      and active/nonsubmissive (a/ns) patterns. A decrease of R-R interval (R-R)
      compared to baseline conditions was found, significantly more pronounced than
      that observed in control animals exposed just to novel environment. R-R
      variability during social stress was positively correlated with the amount of p/s
      behavior. R-R fluctuations, episodes of II degree A-V block, and ventricular
      arrhythmias were also observed. Most R-R fluctuations and II degree A-V blocks
      were temporally associated with phases of p/s behavior and periods of high R-R
      variability. Ventricular arrhythmias generally appeared during a/ns behavior and
      were temporally linked with periods of low R-R variability. Ventricular
      arrhythmias, low R-R variability, and concomitant a/ns behavior might be related
      to an increased sympathetic activity. R-R fluctuations and II degree A-V blocks,
      associated with high R-R variability and p/s behavior, might be related to a
      predominant inhibitory effect of vagal activation (accentuated antagonism).

PMID- 8153158
TI  - An analysis of spatial navigation in prenatally protein malnourished rats.
AB  - Developing rats were either malnourished or adequately nourished during the
      prenatal period by feeding their dams diets of low (6% casein) or adequate (25%
      casein) protein content 5 weeks prior to mating and throughout pregnancy. All
      pups received adequate nutrition from the day of birth onwards. Male offspring
      were tested in one of two spatial navigation tests in the Morris water tank. In
      proximal-cue tests (postnatal days 16-20), the position of a platform, which
      provided a means to escape from swimming, was denoted by an obvious visual cue
      located directly on the platform. In distal-cue tests (postnatal days 20-27 and
      adult ages, days 70-71 and days 220-221), the escape platform was submerged below
      the surface of the water so that the rats were required to use extramaze visual
      cues to guide them to the platform. Neither proximal-cue nor distal-cue
      navigation was significantly impaired in the prenatally malnourished rats
      relative to controls, at any of the ages tested.

PMID- 8153159
TI  - Does taste aversion play a role in the effect of dehydroepiandrosterone in Zucker
      rats?
AB  - Dehydroepiandrosterone (DHEA) reduces food intake in obese Zucker rats. To study
      the role of taste aversion on this process, we used two approaches. First, we
      presented increasing concentrations of DHEA in chow to lean and obese Zucker
      rats, either in competition with unadulterated chow, or alone. Second, we
      examined energy intake following parenteral DHEA administration. Both lean and
      obese rats always preferred nonadulterated chow to DHEA-supplemented chow.
      However, lean rats required a higher DHEA concentration (0.06%) than obese rats
      (0.015%) to achieve the same degree of aversion. When DHEA-supplemented chow was
      presented alone, only high concentrations (0.3 and 0.6% DHEA) decreased food
      intake. Rats given DHEA by IP injection (200 mg/kg/day) also decreased their
      energy intakes. The results demonstrate that although DHEA can cause taste
      aversion at low concentrations in Zucker rats, it does not alter energy intake
      until high concentrations are given. In addition, nonoral DHEA also decreases
      energy intake in these animals. These results suggest that DHEA's antiobesity
      effect is not mediated by taste aversion.

PMID- 8153160
TI  - Home cage behavior of rhesus monkeys with long-term deficiency of omega-3 fatty
      acids.
AB  - In an observational study with a blind observer, rhesus monkeys deficient in
      omega-3 (omega-3 or n-3) fatty acids initiated more bouts of stereotyped behavior
      in their home cages than monkeys fed a matched control diet abundant in omega-3
      fatty acids. Locomotion bouts were also more frequent in deficient monkeys, but
      nonstereotyped locomotion did not differ. Both stereotyped behavior and the sum
      of all behavioral bouts were more frequent in 4-5-year-old than in 2-3-year-old
      monkeys, and stereotype decreased after meals in males but not females. The
      stereotyped behaviors associated with a deficit in omega-3 fatty acids were those
      typical of rhesus monkeys raised as partial social isolates or those whose
      surroundings have been disrupted.

PMID- 8153161
TI  - Participation of pelvic nerve branches in male rat copulatory behavior.
AB  - The role of the pelvic nerve branches in the mediation of copulatory behavior was
      investigated. The somatomotor or the viscerocutaneous branch of the pelvic nerve
      was bilaterally sectioned in sexually experienced male rats. Somatomotor branch
      surgery had no detectable effect. Viscerocutaneous branch transection altered
      copulatory parameters that reflect impairments in penile erection and seminal
      plug emission. The altered behavioral parameters approached or reached
      presurgical and sham values 21 days after transection, indicating that the damage
      to erectile and ejaculatory function was transient. It is suggested that animals
      with viscerocutaneous branch transection recover copulatory efficiency through a
      compensatory plastic mechanism, possibly involving the hypogastric nerve.

PMID- 8153162
TI  - Competitive and territorial fighting: two types of offense in the rat.
AB  - Two types of fighting (offense) were compared and contrasted in three experiments
      on the laboratory rat. In Experiment 1, competitive fighting was obtained in
      pairs of hungry cagemates by placing one food pellet into their food hopper. In
      Experiment 2, territorial fighting was obtained by introducing an unfamiliar
      intruder into the home cage of a male and female pair. Both types of fighting had
      the same motor patterns. Whereas territorial fighting is strongest against
      intruders of the same sex, competitive fighting is stronger against the smaller
      opponent (in this case female) regardless of the sex of the test animal. Whereas
      territorial fighting is stronger in males, competitive fighting is stronger in
      females. Whereas gonadectomy reduces territorial fighting in males but not
      females, it reduces competitive fighting in both sexes. In experiment three, it
      was shown that food deprivation increases competitive fighting, while it reduces
      territorial fighting. On the basis of these findings a revised model of the
      organization of the offense motivational system is proposed.

PMID- 8153163
TI  - Physiology and mechanics of rat levator ani muscle: evidence for a sexual
      function.
AB  - The levator ani (LA) of male rodents is a classic model tissue for the study of
      hormone-muscle interactions, although its functions remain unknown. Recordings
      during copulation from chronic electromyographic (EMG) electrodes in the LA and
      bulbospongiosus (BS) revealed that EMG activity in the LA and BS was tightly
      coordinated. The LA was not active during noncopulatory behaviors, including the
      1-min interval surrounding defecation. Electrical stimulation of the LA motor
      nerves increased penile bulb pressure. Increases in penile bulb pressure
      following BS nerve stimulation were markedly attenuated after LA denervation and
      were reduced further by LA removal. Stimulation of the LA nerve yielded
      insignificant changes in rectal pressure. Perineal motion analysis demonstrated
      that the LA acts upon the penile bulb and the surrounding BS exclusively.
      Apparently the rodent LA muscle is an active component in a highly coordinated
      neuromuscular system augmenting penile erection and, contrary to its name, is
      most unlikely to participate in alimentary function.

PMID- 8153164
TI  - Effects of stimulation of the frontoparietal cortex and parafascicular nucleus on
      locomotion in rats.
AB  - The spontaneous motor activity and locomotion initiated by electrical stimulation
      of the lateral hypothalamus were recorded after electrical stimulation (50-500
      microA, 10-30 Hz, 0.1 ms pulses) of the frontoparietal cortex (FrPaM) and
      parafascicular nucleus of the thalamus (PF). Local injection of kainic acid (KA)
      (0.02 micrograms, 1.0 microliter) was applied to the FrPaM and PF to avoid
      stimulation of descending fibres of passage. The electrical stimulation and KA
      application to the FrPaM and PF produced inhibition of locomotion in freely
      moving rats. In Nembutal-anesthetized (25-30 mg/kg) rats electrical stimulation
      of the FrPaM and PF inhibitory zones blocked the increase of phasic and tonic
      electrical activity of hindlimb muscles elicited by electrical stimulation of the
      lateral hypothalamus (LH) and red nucleus (R). Electrolytic lesion of inhibitory
      zones of the raphe magnus nucleus (RMg) and adjacent areas of gigantocellular
      (Gi) reticular nuclei arrested blocking effects of the FrPaM and PF on motor
      activity and hindlimbs tonus. The results demonstrated a possible role of the
      FrPaM and PF in initiation of locomotor activity inhibition. Interactions of the
      FrPaM and PF with the brain stem inhibitory zones are also discussed.

PMID- 8153165
TI  - The role of serum testosterone in the accelerated extinction of a conditioned
      taste aversion in fluid deprived male rats.
AB  - Fluid deprivation decreases serum testosterone (T) levels and increases the rate
      of extinction of a conditioned taste aversion in Sprague-Dawley male rats. It has
      been suggested that the decreased serum levels may be the primary factor
      responsible for the accelerated extinction rates during fluid deprivation. To
      test the generality of this hypothesis, the effect of fluid deprivation on T
      levels and extinction rate was investigated in Fischer 344 male rats. Extinction
      rates were accelerated in Fischer 344 rats but T levels were not decreased. In a
      second study, the behavioral and hormonal responses of Fischer 344 and Sprague
      Dawley males to fluid deprivation were compared. Extinction rates were increased
      in both strains of rat by fluid deprivation, but serum T levels were decreased in
      fluid-deprived Sprague-Dawley males and not Fischer 344 males. It was suggested
      that the accelerated extinction in fluid-deprived Sprague-Dawley males was
      primarily due to decreases in serum T levels, while the faster extinction in
      deprived Fisher 344 males could be accounted for by decreases in sensitivity to
      T.

PMID- 8153166
TI  - The aversive and hypophagic effects of estradiol.
AB  - Estradiol is known to reduce food intake in many species. Recent studies have
      also shown that estradiol can function as an unconditioned stimulus in taste
      aversion paradigms, suggesting that it induces nausea and malaise in rats and
      mice. The experiments reported here compared the hypophagic and aversive effects
      of estradiol. Using mice as subjects, the first investigation examined the taste
      aversion properties of the estradiol receptor antagonist MER-25, which is
      estrogenic with respect to feeding. MER-25 induced a strong taste aversion,
      contrary to a previous report. Second, progesterone, which counteracts the
      hypophagic effects of estradiol, did not disrupt the taste aversion induced by
      estradiol in mice. The third investigation used the Mongolian gerbil, a species
      in which estradiol increases food intake, in contrast to other species. Despite
      increasing food intake, estradiol induced a conditioned taste aversion in the
      gerbil similar to that seen in rats and mice. Taken together, these results
      indicate that the feeding and aversive effects of estrogen are mediated by
      different mechanisms.

PMID- 8153167
TI  - Ultradian rhythms in avoidance behavior of DBA mice.
AB  - This study investigates ultradian rhythm in avoidance behavior of mice, which may
      constitute a basic rest activity cycle (BRAC). Reaction times (RTs) of an
      avoidance response to a visual warning stimulus that preceded an electric shock
      were measured by the use of a computer-controlled shuttle box. The male naive DBA
      mice were brought to a criterion of 98% correct responses in numerous training
      sessions. For each subject, all the temporal sequences of the RTs in the trials
      following achievement of the criterion were examined with discrete Fourier
      transform. Periodograms were obtained from three sessions for each of the two
      animals in the first experiment and from 15 subjects in the second experiment.
      Analysis of the periodograms reveals a stable rhythm in avoidance behavior of
      mice, with a period of about 14 min. The presence of these periodicities could
      show the existence, also in small rodents, of a BRAC rhythm.

PMID- 8153168
TI  - Crossmodal training reduces behavioral deficits in rats after either auditory or
      visual cortex lesions.
AB  - Rats were trained with either visual or auditory intensity cues until they
      emitted nine avoidance responses in 10 trials (9/10) prior to bilateral ablation
      of the corresponding sensory neocortex. Six days after surgery, rats were trained
      to 5/10 criterion in one of the following conditions: within-modality direct,
      within-modality reversal, crossmodality direct, crossmodality reversal, or no
      training control. The next day all rats were retrained to 9/10 on their
      preoperative tasks. For visual decorticate rats, the no training and the visual
      within-modality direct groups relearned the discrimination at the same rate as
      preoperative learning. Auditory crossmodal direct training enhanced relearning
      more than other forms of training and visual within-modality reversal training
      hindered retraining. For auditory decorticate rats, similar postoperative
      auditory within-modality and visual crossmodality training effects were seen
      during retraining of the auditory discrimination. These findings suggest
      crossmodality training facilitates functional recovery through relational
      information and learning sets transferred from experimental training to the
      relearning task.

PMID- 8153169
TI  - The basal midbrain as a region modulating the level of alerting in the toad, Bufo
      paracnemis.
AB  - Reversible thiopental blockade of sites located in the basal midbrain of
      conscious toads bearing chronically implanted cannulae induced a response in
      which the animal withdrew to the bottom of the experimental box with flexed head
      and forelegs. Partial or total eyelid closure, myosis, and reduced ventilatory
      movements also occurred. No significant changes in arterial pressure levels or
      heart rate occurred and the reflex wiping response to the application of a
      painful stimulus (acid) to the skin was also unaffected. However, the somatic and
      visceral responses to nonpainful stimuli were reduced. There was a decrease, but
      not abolition, of forebrain waves in the 11 Hz range grouped in spindles, perhaps
      due to the reduced ventilatory drive. On the basis of these findings and of
      previous data from our laboratory and others on other nonmammalian groups, we
      postulate the existence of neurons involved in the modulation of behavioral and
      visceral alerting in the basal midbrain.

PMID- 8153170
TI  - Suprachiasmatic lesions eliminate 24-h blood pressure variability in rats.
AB  - To evaluate whether the suprachiasmatic nuclei (SCN) control 24-h rhythmicity in
      cardiovascular function, rats were subjected to computerized recording of 24-h
      blood pressure (BP) and heart rate (HR) following SCN lesions. In sham- and
      nonlesioned rats, circadian patterns of BP and HR ran in phase with those in
      feeding behavior. In SCN-lesioned rats circadian rhythmicity in BP, HR and food
      intake were abolished. Minute-to-minute variation of BP and HR was similar as in
      sham- and nonlesioned rats. We conclude that long-term but not short-term
      variability of blood pressure and heart rate is largely determined by SCN
      controlled activity levels.

PMID- 8153171
TI  - An enrichment object that reduces aggressiveness and mortality in caged laying
      hens.
AB  - The effect on aggressive pecking activity and mortality by an environmental
      enrichment device was examined. In this study, 2955 White Leghorn chickens from
      three different lines were used in six separate experiments. Experiments were
      conducted with chickens during their first or second laying period. Half the
      cages in each experiment were equipped with colored key rings or an enrichment
      object manufactured by Gallus Ltd. (Israel). Experimental and control groups of
      cages were distributed in an alternate serial order for each experiment which
      lasted for 3, 4, 5, 8, 9, and 10 months. The enrichment devices significantly
      reduced aggressive head-pecking behavior and significantly decreased the
      mortality rate from 1.06% per month among the controls to 0.57% among the
      experimental groups.

PMID- 8153172
TI  - Suppression of estrus in female mice by the presence of conspecifics or by foot
      shock.
AB  - The reaction of reproductive system of outbred female mice to crowded conditions
      or electric foot shock was investigated. Both experimental factors inhibited
      estrous cycle, and decidual cell reaction (DCR) was observed after traumatization
      of uterine horns in tested animals. Further investigations showed that corpora
      lutea in females subjected to social stress were significantly larger than those
      in mice stressed by classical stressor. Also, plasma progesterone level increased
      only in females exposed to grouped females. These results indicate that social
      interaction among female mice lead to the development of typical pseudopregnancy,
      whereas inhibition of ovulation and DCR in females subjected to electric foot
      shock are not related to the increase of activity of corpora lutea.

PMID- 8153173
TI  - Physical exercise as a novel antidepressant agent: possible role of serotonin
      receptor subtypes.
AB  - Long-term exercise is associated with an antidepressant effect in patients with
      mild to moderate forms of nonbipolar depression and appears to be a promising new
      approach to its treatment. Adaptive changes in serotonin (5-HT) receptor
      functioning appears to play an important role in mediating the action of various
      antidepressant treatments. We investigated the adaptive changes in behavioral
      sensitivity of the 5-HT receptor subtype following 4 weeks of swimming exercise
      in normal rats, as well as in an animal model of depression (3 week, variety of
      chronic stressors). 5-HT1A autoreceptor sensitivity was assessed by hyperphagic
      response induced by 8-OH-DPAT (0.25 mg/kg, IP); 5-HT1A postsynaptic receptor by 5
      HT syndrome induced by 8-OH-DPAT (0.75 mg/kg, IP), and 5 Me-ODMT (5 mg/kg, IP);
      and 5-HT2 receptor by wet dog shakes response induced by quipazine (1 mg/kg, IP)
      and 5MeODMT (5 mg/kg, IP). It was observed that exercise training in normal rats
      resulted in enhanced sensitivity of the 5-HT2 receptors along with subsensitivity
      of 5-HT1A autoreceptors. Exercise, given prophylactically along with chronic
      stressors, was able to prevent the development of behavioral deficit in the open
      field test, and the animals developed remarkably enhanced sensitivity of 5-HT2
      receptors. This adaptive supersensitivity of 5-HT2 receptor is also seen after
      various antidepressant treatments and may play an important role in mediating the
      antidepressant action of exercise.

PMID- 8153174
TI  - Effects of chronically high doses of the anabolic androgenic steroid,
      testosterone, on intermale aggression and sexual behavior in male rats.
AB  - To determine if chronic exposure to high doses of anabolic androgenic steroids
      (AAS) increase aggression and sexual activity in gonadally intact rats, we
      administered SC injections of testosterone propionate (TP: 1 mg) or propylene
      glycol (PG: as a vehicle control) three times per week for 10 consecutive weeks.
      Weekly tests for male copulation were conducted by pairing each male with a
      sexually receptive female in a glass arena and recording various parameters of
      copulation. Chronic treatment with TP did not alter any parameter of male
      copulation including ejaculation and post ejaculatory interval. Sexually
      experienced males were tested once per week for intermale aggression in a neutral
      environment. For aggression tests, each experimental animal was placed into an
      arena with an opponent male for 15 min. The opponent, a gonadally intact male,
      was used only for the purpose of the aggression test. Frequencies of dominance,
      submissive, threat, and fight postures, as well as approaches were scored for
      each animal. TP-treated males did not differ in body weight from PG-treated
      males, suggesting that the increased aggression was not due to increased body
      mass. The results of this study show that chronic exposure to the anabolic
      androgenic steroid, testosterone, potentiates male aggressive response patterns
      but does not alter male sexual behavior or body weight.

PMID- 8153175
TI  - Repeated stress persistently elevates morning, but not evening, plasma
      corticosterone levels in male rats.
AB  - Repeated exposures to a stressor in our rat model of a chronic stress state cause
      elevated plasma corticosterone levels in the morning for several days after the
      last stressor. However, plasma corticosterone levels are normally characterized
      by a circadian rhythm with low levels for much of the morning and higher levels
      near the onset of darkness. The current experiment examined the question of
      whether the elevated morning levels after stressor exposures were accompanied by
      other changes in this circadian rhythm. Male rats were given restraint-shock
      stressor sessions for 0, 1, or 3 days, after which plasma samples were collected
      for 3 days at 0900 h and at three other times around the circadian peak (1400,
      1800, and 2200 h). Plasma corticosterone levels at 0900 h were elevated for the
      first 2 days after three stressor exposures and for 1 day after a single stressor
      exposure compared to those in nonstressed controls. However, levels at 1400,
      1800, and 2200 h were not different in stressed and control rats on the first 2
      days after stressor exposures. In addition, the amplitude of the corticosterone
      rhythm was suppressed after three stressor exposures, but not after one. This
      decrease in amplitude was mostly due to increased morning levels, inasmuch as the
      evening levels were similar in stressed rats and controls. Because the
      hypothalamic-pituitary-adrenal axis is more sensitive to glucocorticoid feedback
      in the morning, our data suggest that the mechanisms mediating feedback at this
      time of day may be disrupted by repeated stressor exposures.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8153176
TI  - Radial maze performance and open-field behaviours in aged C57BL/6 mice: further
      evidence for preserved cognitive abilities during senescence.
AB  - C57BL/6 mice, aged 2 or 24 months, were tested in a radial maze and observed for
      an 8-min period, repeated on 3 consecutive days, in an open-field situation with
      a novel object. In the eight-arm maze, the number of unrepeated path choices made
      by old mice does not significantly increase with training, whereas it does in
      young mice. Older animals also take significantly longer to solve the task but
      the two age groups do not differ with respect to how many paths they run before
      making the first error or in the strategies used to solve the task. In the open
      field situation, the two age groups differ with regard to grooming and rearing
      behaviour, while in the novelty situation, older animal show a higher level of
      locomotor activity, perform less freezing, and interact more with the novel
      object. Habituation curves for all parameters, except grooming in the open field,
      do not differ between the two groups, thus indicating that this form of
      nonassociative learning does not vary substantially with increasing age. Results
      are discussed in terms of preserved cognitive abilities during senescence in that
      strain.

PMID- 8153177
TI  - Attractiveness of male odors to females varies directly with plasma testosterone
      concentration in meadow voles.
AB  - We examined the hypothesis that differences in androgen concentrations may cause
      differences in the attractiveness of male odors to female meadow voles, Microtus
      pennsylvanicus. Males that were to be used as odor donors were castrated and
      implanted with Silastic capsules filled with no hormone or one of four different
      amounts of testosterone. Four different odors from males were assessed for each
      comparison; the odors were from the anogenital area, feces, urine, and
      posterolateral region. Treatment of scent donor males with the lowest dosage of
      testosterone was not sufficient to increase the attractiveness of their odors
      above that of males receiving no hormone. The three higher dosages increased
      attractiveness in a dose-dependent manner. The shape of the dose-response curve
      differed across scents: two scents reached maximum attractiveness in the middle
      of the dose range and remained there at higher doses, whereas the other two
      scents continued to increase in attractiveness as testosterone titers increased.
      The results suggest that scent glands produce graded signals that reflect
      circulating testosterone titers.

PMID- 8153178
TI  - Glucose polymer taste is not unitary for rats.
AB  - The present studies examined rats' responses to two maltodextrin preparations.
      One maltodextrin, a maltooligosaccharide, had an average chain length of 4.4
      glucose units. The other maltodextrin was a maltopolysaccharide, having an
      average chain length of 22. In 24-h preference tests, rats strongly preferred 1%
      and 5% maltodextrin over water, regardless of the type of maltodextrin offered.
      When given a choice of two maltodextrins, rats preferred the
      maltooligosaccharide, but the degree of preference was influenced by the rats'
      previous experience with maltodextrins. Conditioned flavor aversion experiments
      were conducted to determine whether rats detect qualitative flavor differences
      between the these two maltodextrins. Rats trained to avoid one maltodextrin also
      avoided the other maltodextrin. Nevertheless, rats could be trained to drink
      maltooligosaccharide but avoid maltopolysaccharide; these rats showed no reliable
      tendency to respond to the intensity of maltooligosaccharide flavor. Therefore,
      maltodextrins of varying chain length differ more in flavor quality than in
      flavor intensity. This difference in flavor quality is not attributable to known
      sweet and starch flavors because neither maltodextrin contained much glucose and
      because rats trained to avoid the polysaccharide did not avoid starch. Because
      rats can discriminate between solutions containing only 0.5-1% maltodextrin,
      their ability to discriminate among carbohydrates must be far more acute than
      that of humans.

PMID- 8153179
TI  - Disruption of body temperature and behavior rhythms during reproduction in dwarf
      hamsters (Phodopus).
AB  - The internal gestation and subsequent lactation of mammalian reproduction
      represent a considerable physiological challenge. The extent of disruption in the
      daily rhythm of four parameters, core body temperature, nest attendance,
      activity, and wheel running, was monitored in Djungarian hamster (Phodopus
      campbelli) and Siberian hamster (P. sungorus) females implanted intraperitoneally
      with biotelemetric thermistors. The amplitude of each rhythm decreased during
      late gestation, culminating in a substantial disruption at parturition, and did
      not begin a recovery until the latter third of lactation. In each species, the
      change in the core body temperature rhythm was primarily the result of an
      elevation in light phase body temperature to approximate the normally occurring
      dark phase temperature, although the disruption was more extensive in P. sungorus
      than in P. campbelli. As this maternal hyperthermia is associated with the
      provision of essential heat to the altricial liter, these species differences in
      the vulnerability to hyperthermia may constrain the reproductive success of these
      extreme cold adapted small mammals.

PMID- 8153180
TI  - The effect of perinatal exposure to estrogens on the sexually dimorphic response
      to novelty.
AB  - In this study we investigated the sexually dimorphic anxiety response to a novel
      environment in the absence of estrogens neonatally or in adulthood. There was a
      sexual dimorphism in the plus-maze test after the open-field test, females being
      more active and less anxious. In the absence of estrogens neonatally but not in
      the adulthood, the activity levels were similar to those shown by females, while
      the anxiety level was similar to males. These results suggest the need of a
      normal estrogen environment during the critical period of development for the
      normal differentiation of female anxiety responses to a novel environment.

PMID- 8153181
TI  - Dietary salbutamol and level of protein: effects on the acute stress response in
      pigs.
AB  - Effect on the acute stress response of dietary inclusion of 3 ppm salbutamol
      (beta-2-adrenergic agonist) at two levels of protein were investigated in growing
      pigs (from 25 kg live weight). The trial comprised six litters (blocks) of four
      females allocated randomly to four treatment groups in accordance with a 2 x 2
      factorial arrangement. The response to an open-field test and to an intruder were
      measured at 50 kg live weight. Salbutamol increased immobility and looking,
      reduced total exploration, and increased plasma ACTH after test. At high dietary
      levels of protein, salbutamol also increased the latency to attack. High dietary
      levels of protein reduced standing still, latency to contact a novel object and
      an intruder, and level of plasma cortisol before test. Moreover, high protein
      without salbutamol seemed to reduce the latency to attack an intruder. In
      conclusion, chronic treatment with salbutamol shifted the acute stress response
      in pigs toward a passive response, whereas high dietary level of protein provoked
      an active response, which may have consequences in pig production.

PMID- 8153182
TI  - Dietary variety enhances meal size in golden hamsters.
AB  - The effect of dietary variety on meal size was investigated in golden hamsters.
      Hamsters ate meals (four courses x 12 min/course) in which either the same food
      was offered in all four courses (one of powdered Purina chow, shortcake cookie,
      process cheddar cheese, or milk chocolate) or four different foods were offered
      in successive courses. Total energy intake was significantly greater in the
      variety condition than in any of the single-food conditions. Thus, although
      previous research indicates that the meal size of hamsters is relatively
      resistant to change, hamsters do increase meal size in response to dietary
      variety. This finding indicates that the satiety mechanisms of golden hamsters
      share at least some important features with those of other species.

PMID- 8153183
TI  - Circadian wheel running activity rhythms in two strains of domestic rabbit.
AB  - Results from experiments on two strains of domestic rabbit show that despite
      their hopping gait, circadian locomotor rhythms can be successfully measured
      using running wheels specially designed for large laboratory mammals. Three
      female rabbits of an English outbred strain were monitored in a 13:11 light:dark
      (LD) cycle and in constant light (LL), while 12 Dutch-Himalayan rabbits were
      monitored in a 14:10 LD cycle and constant dark (DD). Much stronger rhythms were
      observed in the latter strain, which under LD conditions showed individuals with
      patterns that varied from nocturnal (n = 5), diurnal (n = 4), crepuscular (n =
      1), and predominantly arrhythmic (n = 2). In DD, 10 rabbits showed strong free
      running rhythms, five with tau (tau) less than 24 h and five longer. The
      predominantly arrhythmic activity pattern in the remaining two made estimation of
      tau difficult. Differences in circadian patterns both under LD and DD were
      unrelated to sex. Results show that locomotor rhythms of the rabbit can be
      measured using the running wheel, the traditional apparatus of chronobiology.
      However, the experiments suggest also that the large-bodied breed of rabbits that
      tend towards obesity, such as the English outbred strain, are relatively inactive
      and that smaller, more active breeds such as the Dutch-Himalayan may be more
      suitable for studying circadian rhythmicity if the running wheel is employed.

PMID- 8153184
TI  - Fluoxetine potentiates nitrazepam-induced behavioral sleep in young chicks.
AB  - Nitrazepam (0.5-10 mg/kg, IP) dose dependently induced behavioral sleep in day
      old chicks. Fluoxetine (0.1-1 mg/kg) did not produce sleep in the young birds,
      but the 5-HT reuptake inhibitor (0.1 and 0.5 mg/kg) potentiated nitrazepam (0.5
      and 1.0 mg/kg)-induced hypnosis. Doses (0.5 and 1 mg/kg) of the benzodiazepine
      that did not produce sleep in any or all the chicks, when administered alone,
      induced sleep in some or all the chicks in the presence of fluoxetine (0.1 and
      0.5 mg/kg). Ketanserin (0.5 and 2.5 mg/kg) effectively antagonized the effect of
      fluoxetine on nitrazepam-induced behavioral sleep. These results suggest that
      enhancement of 5-HT level by fluoxetine may be the mechanism involved in the
      potentiation of nitrazepam-induced sleep in the young chicks.

PMID- 8153185
TI  - Establishment of maternal bonding and its mediation by vaginocervical stimulation
      in goats.
AB  - To investigate the establishment of offspring recognition in mother goats, 11
      females were subjected to two successive 5-min tests with their own kid and an
      alien, 2 h 30 min postpartum. All mothers accepted their own kid, while nine
      rejected the alien. This suggests that in goats, 2.5 h are sufficient for the
      development of an exclusive bond with the kid. We also studied the role of
      physiological factors mediating maternal bonding in this species. Eight of the
      nine goats that rejected alien kids were, therefore, submitted to 5 min of
      vaginocervical stimulation (VCS) immediately following the selectivity tests. Of
      these eight goats, five changed their behavior after VCS and accepted the alien
      kid (0/8 before VCS vs. 5/8 after VCS, p = 0.031). Thus, VCS appears to reduce
      rejection behavior towards alien kids while resulting in a significant increase
      in their rate of acceptance. Underlying physiological mechanisms by which VCS may
      act are discussed.

PMID- 8153186
TI  - Naps after total sleep deprivation in depressed patients: are they
      depressiogenic?
AB  - Total sleep deprivation (TSD) exerts beneficial but transient effects on mood in
      approximately 60% of patients with a major depressive disorder. The positive
      effects of a night of total sleep deprivation are generally reversed after the
      next night of sleep. Several anecdotal reports and a pilot study by our group
      indicated that even short naps during the period of sleep deprivation are capable
      of re-inducing depressive mood in responders to TSD. The present study explored
      whether the structure of naps at 9 a.m. was crucial for the "depressiogenic"
      impact of naps on mood. A negative effect on mood was replicated, but this effect
      was not related to any of the nap sleep variables. The effect of naps on mood was
      attenuated in the early afternoon. The results support the assumption of a
      "depressiogenic" effect of naps in patients with major depression after
      successful TSD.

PMID- 8153187
TI  - Electroencephalographic sleep studies in depressed patients during long-term
      recovery.
AB  - Analytic electroencephalographic (EEG) sleep procedures were used to examine
      specific changes in rapid eye movement (REM) and slow wave sleep (SWS) as they
      unfolded during depressive illness and recovery. The subjects were 15 patients
      with recurrent depression who remained well during 3 years of nonpharmacologic
      maintenance treatment without a recurrent episode of major depression. The
      analyses were performed on EEG sleep studies conducted before acute treatment,
      after 3 months in maintenance treatment, and every 3 months thereafter for 3 full
      years of maintenance treatment. There was no change between the index sleep and
      sleep during the first year of maintenance treatment as determined by period
      analysis or visual inspection of REM sleep parameters, except that average REM
      counts decreased over time. Thus, it is possible that REM parameters may
      represent one indicator of long-term recovery from depression. Finally, a
      significantly higher amount of 12-20 Hz spectral power density was found during
      the index episode than during the period of remission.

PMID- 8153188
TI  - Correlation of nocturnal penile tumescence and daytime affect intensity in
      depressed men.
AB  - Although depressed patients have been shown to have diminished nocturnal penile
      tumescence (NPT), there remains considerable variability of NPT in depression. We
      hypothesized that affective experience during the day accounts for some of this
      variability. Forty-five depressed men had assessments of affect intensity and
      affect balance, NPT, and daytime sexual function, both before and after treatment
      with Beck's cognitive behavior therapy (CBT). Forty-three normal control subjects
      were studied for comparison. Daytime affect intensity in depressed men, but not
      in control subjects, correlated significantly and positively with measures of NPT
      duration and rigidity both before and after treatment, regardless of the adequacy
      of daytime sexual function. When the effect of daytime affect on REM activity was
      controlled, the observed correlations became nonsignificant at pretreatment, but
      remained significant at posttreatment. Neuropharmacologically mediated changes in
      arousal responsivity associated with depression may underlie the observed
      relation between daytime affect intensity, rapid eye movement activity, and NPT.

PMID- 8153189
TI  - Event-related potential and clinical correlates of neurodysfunction in obsessive
      compulsive disorder.
AB  - The current study confirmed with increased sample sizes our preliminary findings
      of event-related potential (ERP) abnormalities in obsessive-compulsive disorder
      (OCD) (Towey et al., 1990) and examined their relationship to symptom severity,
      treatment response, and neurological soft signs. Unmedicated patients (n = 17)
      showed larger negativities in N200 and slow wave regions than normal control
      subjects (n = 16) to correctly detected auditory "oddball" stimuli. N200
      amplitude was larger over left than right hemispheres of OCD patients, but not
      normal control subjects. Greater N200 amplitude correlated with less severe
      obsessions, better response to subsequent treatment with serotonin reuptake
      blockers, and fewer neurological soft signs in OCD. With increased task
      difficulty, N200 and P300 latencies lengthened for normal subjects, but not for
      OCD patients. The abnormal ERP pattern in OCD supports hypotheses of cortical
      hyperarousal and overfocused attention.

PMID- 8153190
TI  - Visual attention in obsessive-compulsive disorder.
AB  - Performance on neuropsychological tasks was compared in 15 subjects with
      obsessive-compulsive disorder (OCD) and 15 age- and sex-matched psychiatrically
      screened control subjects. The tasks chosen are known from studies in other
      patient groups to demonstrate lateralized abnormalities of visual and limited
      capacity attentional impairment. The Posner task performance of the OCD group
      demonstrated decreased inhibition of return for left visual field targets and no
      inhibition of return for right visual field targets. The OCD group's spatial
      linguistic conflict task responses were significantly slowed in the conflict
      condition, as predicted. The results are discussed in relation to the
      phenomenology of OCD and prior neuropsychological evaluations.

PMID- 8153191
TI  - Effects of phototherapy on electrooculographic ratio in winter seasonal affective
      disorder.
AB  - Low electrooculographic (EOG) ratios have been reported in patients with seasonal
      affective disorder (SAD). This study was undertaken to replicate these results
      and to consider the effects of light therapy on the EOG in SAD patients. Sixteen
      outpatients with SAD and 16 age-, sex-, and medication-matched control subjects
      had EOG testing before and after 1 week of light therapy during the winter. The
      EOG ratios in the SAD patients were only marginally lower than those in the
      normal control subjects. These differences persisted after light therapy.
      Although the slightly decreased EOG ratios in SAD patients might have resulted
      from an artifact of test variability, drowsiness, or other confounding factors,
      the difference between patients and control subjects raises the possibility of
      retinal abnormality in SAD.

PMID- 8153192
TI  - Empathy, new beginnings, and analytic cure.

PMID- 8153193
TI  - Changing conceptions of the good mother in psychoanalysis.

PMID- 8153194
TI  - Procrastination: its role in transference and countertransference.

PMID- 8153195
TI  - Chance, structure, stress: the birth and development of the human mind-brain.
AB  - Recent physiological studies of the human mind-brain lend support to the theory
      of object relations, and in particular to the manner in which the object of the
      early period enters the infant's dawning psyche to elicit a perdurable pattern of
      both positive and negative response to stimuli. The psychoanalytic concept of
      reactivation, and the psychoanalytic view of language as (in part) a substitute
      for the absent object, are linked with specific cerebral mechanisms to disclose
      the bodily realities that underlie emotive disturbance.

PMID- 8153196
TI  - "The dread voice is past": death and guilt in Milton's Lycidas.

PMID- 8153197
TI  - Perceived gender roles of managers and effective conflict management.
AB  - This study examined the perceived conflict-management behavior and effectiveness
      of 45 managers who had been rated by 230 subordinates as representing masculine,
      feminine, or androgynous gender-role types. Analysis indicated that managers
      perceived by their subordinates as being androgynous were rated as better
      handlers of conflict situations than their masculine or feminine peers.

PMID- 8153198
TI  - Childhood trauma and the origins of paranormal belief: a constructive
      replication.
AB  - Previous research suggests that, as a group, people who believe in the paranormal
      tend to have a history of traumatic events in childhood. This relationship has
      been incorporated into Irwin's 1993 model of the psychological origins and
      functions of paranormal belief. A constructive replication of the relationship
      and a test of Irwin's model was undertaken in relation to a specific context,
      namely, a childhood spent with an alcoholic parent. Compared to 89 control
      participants, a sample of 32 adults who were children of alcoholics had stronger
      beliefs in witchcraft, superstitions, and precognition. The results are discussed
      in relation to two components of Irwin's model.

PMID- 8153199
TI  - Psychosocial modifiers of psychopathology for domestically violent and nonviolent
      men.
AB  - Personality characteristics of 99 domestically violent and 71 nonviolent men were
      studied, using the Millon Clinical Multiaxial Inventory and controlling for
      premorbid history. Men with poor premorbid backgrounds from 3 groups (ns = 66,
      12, and 23) showed more elevations on the Millon inventory than men with good
      premorbid backgrounds (ns = 33, 20, and 48). However, over-all, batterers showed
      more Millon elevations than nonviolent men. These findings point to the need to
      control psychosocial variables when studying personality characteristics of
      batterers.

PMID- 8153200
TI  - Gender differences and similarities in coping responses to anticipated work
      family conflict.
AB  - This study examined the relationships among gender, coping, and anticipated work
      family conflict for career-bound men and women. 256 university students enrolled
      in a university in northern Louisiana participated. Multivariate and univariate
      analyses were used to examine (a) potential gender differences with respect to
      anticipated work-family conflict and work-family coping mechanisms and (b) the
      role coping processes may play in mediating the relationship between gender and
      anticipated work-family conflict. The results indicated significant differences
      between the sexes with respect to anticipated work-family conflict as well as to
      expected use of various coping strategies to manage anticipated work-family
      conflict. Contrary to expectations, coping strategies did not mediate the
      relationship between gender and work-family conflict. The issue of coping as a
      mediator variable as well as the study's primary implications for students and
      professional educators are addressed.

PMID- 8153201
TI  - The Student Alcohol Questionnaire: an updated reliability of the drinking
      patterns, problems, knowledge, and attitude subscales.
AB  - The reliabilities of the Quantity/Frequency Patterns, Problems Resulting from
      Drinking, Knowledge of Alcohol, and Attitudes Toward Drinking subscales of the
      Student Alcohol Questionnaire were calculated. The Spearman-Brown reliability
      coefficients of the subscales were .84, .89, .85, and .27, respectively. Values
      of Cronbach alpha for the four subscales were .86, .92, .86, and .55,
      respectively.

PMID- 8153202
TI  - Broad factor scales of the 16 PF Fifth Edition and Millon personality disorder
      scales: a replication.
AB  - This study is a replication of the link between broad personality factors from
      the 16 PF and personality disorder scales based on Millon's typology of
      personality. The current study was done with the new version of the 16 PF during
      the final stages of norming. The sample consisted of 30 female and 2 male
      undergraduate and graduate students, ranging in age from about 21 to 60 years.
      The data from this replication are consistent with results of the earlier study
      in that 15 of the 18 expectations were in the expected direction. Of these 10
      were significant.

PMID- 8153203
TI  - Methods of suicide used by Irish and Japanese samples: a cross-cultural study
      from 1964 to 1979.
AB  - In this study were compared 8 methods of suicide by sex in three different
      nations over a 16-yr. period. Frequencies by sex showed statistically significant
      preference for method of suicide. Trend analyses by method of suicide by sex and
      nation indicated 19 were statistically significant.

PMID- 8153204
TI  - Church attendance, religiosity, and health.
AB  - Many studies have reported a beneficial effect of church attendance on one's
      health. Little attempt has been made, however, to ascertain what aspect of the
      behavior might be responsible for the effect, so church attendance, religiosity,
      and health were examined in a sample of 174 graduate students (ages 19 to 69
      years). Neither attendance nor religiosity was significantly associated in this
      sample with the frequency or seriousness of illness experienced over the previous
      12-mo. period. These findings are discussed in relation to sample
      characteristics.

PMID- 8153205
TI  - WISC-R subtest reliability over time: implications for practice and research.
AB  - This study investigated the test-retest reliabilities of the WISC-R IQs and
      scaled scores on subtests over 3- and 6-yr. intervals for a learning disabled
      sample. Statistical procedures and individual analyses were conducted on a sample
      of 107 students who had at least two evaluations. For the total sample, 3-yr.
      test-retest reliabilities of the Verbal IQ, Performance IQ, and Full Scale IQ
      were .69, .72, and .77, respectively. Subtest reliabilities ranged from .33 to
      .71, with a median of .49, but nine subtests had reliabilities of .62 or lower.
      Individual analyses indicated considerable variability, with some students
      decreasing as much as 33 IQ points on retest. Similar results were noted for a
      subsample of 41 students who had three evaluations over a 6-yr. period. Problems
      with subtest interpretation due to the inconsistency of the WISC-R scores and
      extensions of this research to the WISC-III are discussed.

PMID- 8153206
TI  - Long-term stability of individual WISC-R IQS of learning disabled children.
AB  - Stability of IQ for race and gender was examined by analyzing the results of two
      administrations over 3 years of the WISC-R for 402 learning disabled children.
      About 50% of the variance in Test 2 was accounted for by scores on Test 1.
      Frequency of positive or negative difference for each IQ from Test 1 to Test 2
      was presented. Direction of change in IQ was negative for the Verbal Scale and
      positive for changes on the Performance Scale.

PMID- 8153207
TI  - Validity of the MMPI-2 Depression content scale with psychiatric inpatients.
AB  - The concurrent and construct validity of the MMPI-2 Depression content scale was
      examined for a group of 62 psychiatric inpatients. Correlation coefficients with
      other measures of depression, hopelessness, low self-esteem, and suicide ideation
      ranged from .58 to .66 and were statistically significant. Also, the Depression
      content scale successfully differentiated patients according to psychiatric
      diagnosis (depressed versus nondepressed) and assessed suicide risk (at risk
      versus not at risk). Thus, the concurrent and construct validities of the scale
      were supported.

PMID- 8153208
TI  - Effects of a TV drama series upon public impressions about psychiatrists.
AB  - A survey was conducted among a nationally representative sample of over 2,800 UK
      television viewers to examine audience reactions towards a drama series about
      psychiatry. Whilst the majority of respondents agreed that the drama Shrinks was
      good entertainment and gave a realistic view of the field of psychiatry, those
      who reportedly had a close association with a mentally ill person were less
      likely to find the characterisations of the patients and psychiatrists credible.
      Despite the misgivings of practising psychiatrists and clinical psychologists,
      however, no evidence was found to support the idea that watching the drama
      resulted in misconceptions about the real world of psychiatric medicine.

PMID- 8153209
TI  - Gender rivalry and attitudes toward sex roles: changes over a fifteen-year
      period.
AB  - Two samples (ns = 80) of men and women tested 15 years apart were observed to
      respond differently under rivalry conditions. Comparison of scores on a scale
      designed to measure attitudes to sex roles indicated a significant change during
      the 15-year period which may account for the change in behaviour observed during
      rivalry.

PMID- 8153210
TI  - Validating the Street Survival Skills Questionnaire.
AB  - The utility of the Street Survival Skills Questionnaire was investigated using a
      sample of 18 trainable mentally retarded males attending public schools. Pearson
      product-moment correlations were computed among the total scores, four standard
      scores on the Vineland Adaptive Behavior Scale-Survey Form, and three Wechsler
      Intelligence Scale for Children-Revised IQs. The Street Skills scores correlated
      significantly with Vineland Daily Living scores and WISC-R Full Scale and
      Performance IQs; however, nonsignificant relationships were obtained with WISC-R
      Verbal IQs, Vineland Composite scores, Communication Domain scores, and
      Socialization Domain scores. The use of the questionnaire in assessment of
      adaptive behavior was supported but within a narrow scope, i.e., daily or
      functional living knowledge.

PMID- 8153211
TI  - Measuring the poles of negative and positive mood using the Positive Affect
      Negative Affect Schedule and Activation Deactivation Adjective Check List.
AB  - The Positive Affect Negative Affect Schedule (PANAS) has become one of the most
      widely used measures of mood. It was developed from research using responses to
      adjective checklists as empirical evidence for the two independent, bipolar
      factor model of mood. However, when scores on the PANAS were factor analyzed with
      those from another mood checklist, Thayer's Activation Deactivation Adjective
      Check List, the PANAS represented only half of the model proposed by Watson and
      Tellegen (1985) by not containing adjectives representing the lower poles of
      positive and negative affect.

PMID- 8153212
TI  - Cross-validating a causal model relating attributional style, self-esteem, and
      depression: an heuristic study.
AB  - Pillow, West, and Reich, using path analysis in 1991, were unable to confirm the
      causal model predicted from the reformulated learned helplessness theory of
      Abramson, Seligman, and Teasdale which links the dimensions of attributional
      style with self-esteem and depression. Because their failure to confirm the model
      may have been due to their using normal subjects instead of psychiatric patients,
      the model was retested in the present study on psychiatric patients, many of whom
      had been diagnosed as depressed. Although the Abramson, et al. model was once
      again not confirmed, neither was the alternative model proposed by Pillow, et al.
      The model that fitted the data best in this study differed from both of these
      models and indicated that all three attributional dimensions affect depression
      solely through the mediation of self-esteem.

PMID- 8153214
TI  - Indian identification and alienation in an urban community.
AB  - Studies of alienation among Native Americans have been few. Reliance on
      sociological and psychological themes is commonplace in explaining Native
      Americans' alienation. This project was designed to explore the relationship
      between alienation and Native Americans' identification (26 men, 27 women) in an
      urban setting. Analysis generated correlations for scores on alienation with age,
      years of schooling, years of living in the city, percentage of Indian blood, self
      rating of Indian identity, and Indian pride which were affected by gender.

PMID- 8153213
TI  - Update on AIDS and sexual behavior of college students: seven years later.
AB  - This survey of 54 single, sexually active college students indicated that there
      has been a significant increase in concern about AIDS compared to a survey on a
      similar sample in 1985. A majority of this sample have been involved in
      monogamous relationships during the past year and 35% have had the AIDS test on
      which no seropositive results were reported. Yet, despite an increase in AIDS in
      the nation's heterosexual population, the majority of students continue to engage
      in unprotected sexual relations. Nevertheless, the over-all pattern of results
      suggests that there has been a clear shift toward more conservative sexual
      practices compared to the casual lifestyles during the pre-AIDS era and the early
      1980s.

PMID- 8153215
TI  - Pregnancy termination, perceived control, and perinatal grief.
AB  - In a group of 30 women who underwent induced delivery after they had been
      informed of a lethal fetal anomaly, 18 women reported that this was the outcome
      of a clear decision process and 12 reported that they had no choice. In contrast
      to findings in other research areas, the experience of having perceived control
      was not associated with lower grief scores three months after perinatal loss.

PMID- 8153216
TI  - Comparison of Indonesian and American college students' attitudes toward
      homosexuality.
AB  - Indonesian and U.S. college students were compared to assess whether an
      interaction of sex of subject by sex of target on attitudes toward homosexuals
      would be replicated cross-culturally. The Indonesian sample was expected to hold
      more traditional attitudes toward women's gender-role behavior which was expected
      to override the interaction of sex of subject by sex of target. Knowledge of AIDS
      was expected to be correlated with attitudes toward homosexuals. Analysis showed
      that the interaction of sex of subject by sex of homosexual target was present in
      both samples. Knowledge of AIDS was correlated with attitudes toward homosexuals
      for the U.S. sample but not for the Indonesian sample. Attitudes toward women's
      gender-roles were correlated with attitudes toward homosexuals in both samples.

PMID- 8153217
TI  - Perceived and actual mathematical competencies of children with visual
      impairments and learning disabilities.
AB  - This study compared 5 visually impaired learning disabled children's perceived
      and actual mathematical competencies. Analysis indicated that their competencies
      were significantly different.

PMID- 8153218
TI  - Social acceptance by their peers of children with mental retardation.
AB  - Students' willingness to befriend a child with mental retardation was
      investigated using written vignettes of students said to be enrolling in the
      subjects' school. In the control condition, all stories described the incoming
      students as non-labeled peers. In the experimental condition, half of the
      descriptions of new classmates included the addition of the label mentally
      retarded. Subjects were asked to make a behavioral commitment to befriend an
      incoming student assuming that the child would be joining their class. Chi
      squared analysis indicated that the addition of the label to a description of a
      child significantly reduced the frequency of that child's being selected by
      subjects, particularly boys. The data suggested that the label may inhibit
      students' willingness to accept labeled peers socially.

PMID- 8153219
TI  - Bulimic women's perceptions of interaction within their families.
AB  - The association between women's perceptions of the interaction within their
      families and symptomatology related to eating was investigated in a case series
      of 81 women suffering from bulimic disorders. Bingeing was more frequent when the
      family was perceived to have poor problem-solving skills but was less frequent
      when the women perceived their families as having a more cohesive style. In
      contrast abnormal restriction of intake was linked, although not significantly,
      to the converse pattern of perceived interaction within the family--greater when
      the family was relatively cohesive and lower when the family had good problem
      solving skills. The same family characteristics appear to be 'risky' for some
      symptoms and 'protective' against others.

PMID- 8153220
TI  - Posttraumatic stress disorder in male and female Dutch Resistance veterans of
      World War II in relation to trait anxiety and depression.
AB  - In this study, 680 male and 144 female Dutch Resistance veterans of World War II
      were evaluated on Posttraumatic Stress Disorder, trait anxiety, and depression.
      Approximately 27% of these men and 20% of these women showed current
      Posttraumatic Stress Disorder. Resistance veterans, as a group, appeared
      comparable to the controls from Dutch validation studies on trait anxiety and
      depression. Gender differences were not observed. Veterans with current PTSD
      symptoms scored higher on trait anxiety and depression than the remaining
      veterans and were comparable on trait anxiety and depression to psychiatric
      patients. Correlational analyses showed that there was a strong association
      between trait anxiety and depression. Posttraumatic Stress Disorder correlated
      highly with trait anxiety and depression.

PMID- 8153221
TI  - Trait anxiety and perception of a potential nuclear power plant disaster.
AB  - This study explored how trait anxiety interacts with various demographic
      variables in influencing how potential nuclear power disaster is assessed by a
      random sample of 150 adults (77 women, 73 men) who live near a nuclear power
      plant. Expectation of a future nuclear power plant disaster was positively
      related to high trait-anxiety elevations in women who were childless.

PMID- 8153222
TI  - "Wet" or "dry" county status and its correlates with suicide, homicide, and
      illegitimacy.

PMID- 8153223
TI  - Applicability of the Revised Diagnostic Interview for Borderlines to hospitalized
      adolescents.
AB  - Administration of the Revised Diagnostic Interview for Borderlines to 14
      adolescent girls showed that the 10 who had chart diagnoses of Borderline
      Personality Disorder or such features earned significantly higher scores than the
      4 nonborderline adolescents. The small sample warrants replication but results
      suggest the interview seems appropriate in research with adolescent girls.

PMID- 8153224
TI  - The position of sex-typical words in two-dimensional emotion space.
AB  - Data from five experiments (total N = 304) were used to examine differences in
      assignments of sex-typicality to personality-describing words. The several
      significant differences were interpreted in terms of the location of male-typical
      and female-typical words in two-dimensional emotion space. Words judged as
      typical of women were consistently more pleasant and less active than those
      judged as typical of men. The report includes tables of over 200 sex-typical
      words.

PMID- 8153225
TI  - Effects of Title X "gag rule" upon women's attitudes towards their healthcare
      providers.
AB  - 79 women were randomly assigned to conditions in which they received pregnancy
      counseling including abortion information or excluding abortion information (with
      or without a reminder of the "gag rule"). Subjects not given abortion information
      viewed their caregivers as more biased, less competent, less empathetic, and
      holding anti-abortion views compared to those receiving such information. Those
      not given abortion information but reminded of the "gag rule" viewed their
      caregivers with relative dislike and mistrust.

PMID- 8153226
TI  - Love-styles among university students in Mexico.
AB  - 146 university students from Mexico, representing four different majors of
      accounting, chemistry, philosophy and arts, and technical subjects, were
      administered the Sample-Profile of love-styles. Comparisons of magnitude of
      endorsement and rankings of six love-styles showed differential patterns of love
      attitudes. Strong endorsement was found for a love-style profile characterized by
      a calm, deliberate, and compassionate love.

PMID- 8153227
TI  - Gender differences in dream perspectives.
AB  - A study exploring gender differences in self-reported dream perspectives was
      performed with 282 college students. Significantly more of the 164 women reported
      dreaming exclusively in first person and more of the 114 men exclusively in third
      person. Also, gender differences were found for those who dreamed in mixed
      perspective, a combination of first- and third-person points of view. Possible
      reasons for these differences were suggested and further research posited.

PMID- 8153228
TI  - Reconceptualizing support systems for persons with challenging behaviors.
AB  - As human service systems attempt to integrate persons with disabilities,
      particularly those with challenging behaviors, into the mainstream of society,
      use of positive behavioral supports must be implemented. Training of persons in
      the formal and informal support systems must also be reconceptualized in the
      context of using positive behavioral supports. This paper addresses some current
      issues related to the use of such supports and training in the delivery of human
      services.

PMID- 8153229
TI  - Internal consistency and stability of the Attitudes Toward AIDS Scale-High School
      Version.
AB  - Reliabilities of the Attitudes Toward AIDS Scale-High School Version were
      estimated for a sample of 170 adolescents. Cronbach alpha of .79 and a stability
      coefficient of .84 were obtained.

PMID- 8153230
TI  - Relationship between personality disorders and clinical symptoms in psychiatric
      inpatients as measured by the Millon Clinical Multiaxial Inventory.
AB  - The Millon Clinical Multiaxial Inventory is a 175-item psychodiagnostic
      instrument which is based on Millon's theory of psychopathology, in which Millon
      suggests clinical symptoms result from an exacerbation of an individual's
      personality style when under stress. The purpose of the present study was to
      examine the relations of personality disorders to clinical symptoms as measured
      by the inventory. The sample of 245 inpatients from a state psychiatric hospital
      completed the Millon inventory between January, 1987 and April, 1989. Stepwise
      multiple-regression analyses were conducted to ascertain the relationship between
      personality disorders and symptoms. The 9 clinical symptom scales served as
      criterion variables while the personality-disorder scales served as predictor
      variables. The results were generally consistent with expectation and are
      discussed in terms of Millon's theory.

PMID- 8153231
TI  - Influence of sexual preference cues on rating applicants for a teaching position.
AB  - Subjects differentially evaluated one excellently qualified candidate for a
      teaching position in Grade 4 as a function of varied informal notes attached to
      an application. The three variations were heterosexually cued behaviors,
      homosexually cued behaviors, and no cues. This application was presented along
      with four other standardized applications to which informal notes were also
      attached. The application was rated most favorably by the subjects when the
      heterosexually cued behaviors were present, and least favorably when homosexually
      cued behaviors were present. In addition, men displayed more discriminative
      behaviors in their ratings than did women.

PMID- 8153232
TI  - Similarities in Type A behavior between young children and their parents in
      Japan.
AB  - In Japan similarities in Type A behavior between preschool children and their
      parents were investigated. Type A scores of 169 pairs of sons and their fathers,
      130 pairs of daughters and their fathers, 158 pairs of sons and their mothers,
      and 121 pairs of daughters and their mothers were measured on the Japanese
      version of the Matthews Youth Test for Health for children and KG's (Kwansei
      Gakuin) Daily Life Questionnaire for parents. Self-ratings on the Hard-driving
      and Time-urgent scale of parents were correlated positively with teachers' Type A
      ratings of their sons, but no associations were found between scores of parents
      and their daughters. These results might be consistent with the hypothesis that
      children might learn Type A behaviors when their parents do not show much
      interest in child-rearing.

PMID- 8153233
TI  - Computer-administered visual analogue mood scales: rapid and valid assessment of
      mood in HIV positive individuals.
AB  - Studies of cognition in patients with the human immunodeficiency virus must take
      into account the effects of mood. Standardised mood-rating questionnaires are
      oftentimes consuming and fatiguing for such patients and so may be omitted from
      experiments. Visual analogue rating scales for affective state are rapidly
      administered and are quite acceptable to subjects. In 64 HIV seropositive
      homosexual or bisexual males, measures of anxiety and depression derived from two
      computer-administered visual analogue scales were compared with anxiety and
      depression ratings from the Spielberger State-Trait Anxiety Inventory and the
      Center for Epidemiological Studies-Depression. Analogue ratings of anxiety
      correlated .80 with STAI State anxiety and .58 with STAI Trait anxiety measures
      and analogue ratings of depression correlated .78 with CES-Depression measures.
      Analogue ratings may differentiate situational anxiety and depression more
      effectively and so are valid tools in assessment of anxiety and depression in HIV
      seropositive subjects. These may be of particular value when limitations of time
      or patient illness require a rapid assessment of mood variables in
      neuropsychiatric research.

PMID- 8153234
TI  - Predictors of coping strategies among adults with cancer.
AB  - The predictive utility of emotional distress, social support, and satisfaction
      with health care for use of particular coping strategies (confrontation,
      avoidance, acceptance-resignation) was examined in 130 adults with cancer.
      Analysis indicated that emotional distress was the most salient predictor of
      adults' use of coping strategies characterized by avoidance and acceptance
      resignation, after controlling for the effects of duration of disease and
      relevant demographic characteristics. Emotional distress, social support, and
      satisfaction with health care did not account for a significant percentage of the
      variance in coping strategies characterized by confrontation.

PMID- 8153235
TI  - Children's attitudes toward the mentally ill: an eight-year longitudinal follow
      up.
AB  - In 1986, Weiss reported the measurement of the attitudes of 577 children of
      elementary school age toward mental illness and mentally ill persons relative to
      other stigmatized groups on a projective measure of social distance. It was
      concluded that attitudes toward deviant groups were evidenced by Kindergarten and
      did not change appreciably with increasing age or grade. Eight years later, 35 of
      the previously examined 65 Kindergarten students were still enrolled in the
      district. Parental permission to repeat the evaluation was received for 34 of
      those students. The results of this longitudinal research were remarkably similar
      to the results in the original cross-sectional research, again leading to the
      conclusion that attitudes toward the mentally ill become quite stable and
      enduring by the time a child enters Kindergarten. Only one stigmatized group,
      mentally retarded persons, significantly changed in terms of social distance and
      interpersonal attraction toward being more acceptable.

PMID- 8153236
TI  - Diverging gender attitudes regarding causal sex: a cross-sectional study.
AB  - Students at five educational levels ranging from seventh graders to college
      seniors were surveyed regarding their attitudes about the acceptability of casual
      sex. A striking developmental contrast was found: males became increasingly
      accepting of casual sex; females were consistently opposed to casual sex at all
      educational levels.

PMID- 8153237
TI  - Psychometric evidence that mercury from silver dental fillings may be an
      etiological factor in depression, excessive anger, and anxiety.
AB  - Scores on the Beck Depression Inventory were compared for 25 women who had silver
      dental fillings (amalgams) and for 23 women without amalgams. Women with amalgams
      had significantly higher scores and reported more symptoms of fatigue and
      insomnia. Anger scores from the State-Trait Anger Expression Inventory showed
      that the women with amalgams had statistically significantly higher mean scores
      on expressing anger without provocation and experiencing more intense angry
      feelings. The women without amalgams scored significantly higher on controlling
      anger, which suggested they invested more energy in monitoring and preventing the
      experience and expression of anger. Anxiety scores from the State-Trait Anxiety
      Inventory showed the women with amalgams scored significantly less pleasant,
      satisfied, happy, secure, and steady, and had a more difficult time making
      decisions. They had significantly higher Trait Anxiety scores. The women with
      amalgams also had significantly higher levels of mercury in the oral cavity
      before and after chewing gum. The study suggests that amalgam mercury may be an
      etiological factor in depression, excessive anger, and anxiety because mercury
      can produce such symptoms perhaps by affecting the neurotransmitters in the
      brain.

PMID- 8153238
TI  - Clinical and research attitudes of Psy.D. and Ph.D. clinical graduate students.
AB  - A survey of 137 Psy.D. and Ph.D. clinical graduate students out of 561 at 4 Ph.D.
      schools and 4 Psy.D. schools indicated that these Ph.D. students found knowledge
      of statistics and research design to be more useful than the 98 Psy.D. students.
      A need to replicate and to ascertain the basis for such differences was
      discussed.

PMID- 8153239
TI  - Development of a driving anger scale.
AB  - A cluster analysis of responses from more than 1500 college students to 53
      potentially angering driving-related situations yielded a 33-item driving anger
      scale (alpha reliability = .90) with six reliable subscales involving hostile
      gestures, illegal driving, police presence, slow driving, discourtesy, and
      traffic obstructions. Subscales all correlated positively, suggesting a general
      dimension of driving anger as well as anger related to specific driving-related
      situations. Men were more angered by police presence and slow driving whereas
      women were more angered by illegal behavior and traffic obstructions, but
      differences compensated so there were no gender differences on total score. A 14
      item short form (alpha reliability = .80) was developed from scores more highly
      correlated (r = .95) with scores on the long form. Driving anger may have
      potential value for research on accident prevention and health psychology.

PMID- 8153240
TI  - Fathers' involvement and responding to infants: "more" may not be "better".
AB  - It is commonly suggested that "more" involvement by fathers in infants' routine
      care may be "better"; however, support for this position is not conclusive. In
      the study reported here, a significant negative relationship was found between 27
      fathers' involvement in their infants' care and positive responding to their
      infants in an observational setting. Several explanations are explored and
      discussed.

PMID- 8153241
TI  - Socioeconomic status and the Rorschach.
AB  - People from lower socioeconomic status are making increasing use of mental health
      facilities. Surveys have indicated that the Rorschach is still one of the more
      frequently used instruments by psychologists in such facilities, but research has
      also shown that clinicians tend to misinterpret Rorschachs of people from the
      lower socioeconomic group as reflecting greater psychopathology than the same
      Rorschachs identified as being given by people from the middle class. Research
      has also shown that growing up in conditions of poverty significantly affects how
      people perform on tests of abstract thinking, tests of intelligence, and tests of
      academic achievement; the question was raised as to whether this extends to the
      Rorschach. The lack of sufficient research on the effect of socioeconomic status
      on responsiveness to the Rorschach precluded that question being answered. The
      kind of research still needed was discussed.

PMID- 8153242
TI  - Effects of age, sex, and university status on life-satisfaction.
AB  - Diener, et al.'s 1985 Satisfaction With Life Scale was administered to 1749 adult
      Australians to examine differences between men and women, university students and
      nonuniversity students, and among 17- to 22-, 23- to 29-, and 30- to 40-yr.-olds.
      No significant differences in life-satisfaction emerged in relation to sex or
      university status, but age showed a significant effect as higher life
      satisfaction characterized older subjects. No interactions were found for any
      combination of the three variables. The results are interpreted in terms of
      egalitarian sex-role ideologies regarding sex, status-specific criteria in the
      assessment and conceptualisation of life-satisfaction for university status, and
      maturity trends in viewing life events concerning age.

PMID- 8153243
TI  - Working-memory capacity and reading comprehension in young and older adults.
AB  - This study investigates the role of working-memory capacity in reading
      comprehension in young and older subjects. A task yielding separate measures for
      processing and storage components was used to assess working-memory capacity. A
      French version of the Nelson-Denny test was administered as a measure of
      abilities that underlie reading comprehension. In the working-memory task, recall
      performances were lower in older subjects. Nevertheless, the intercorrelations
      suggested that the age-related impairment was probably linked to the processing
      component. Mean scores on the reading-comprehension test did not differ between
      groups. However, scores were correlated with processing time on the working
      memory task in younger subjects, but with storage capacity in older subjects.

PMID- 8153244
TI  - The relationship between latency of auditory evoked potentials, simple reaction
      time, and stimulus intensity.
AB  - The effects of loudness on the latency of evoked potentials and on simple
      reaction time were compared. It was found that both reaction time and the evoked
      potential latency increases with decreasing stimulus intensity. However,
      different slopes of the curves were found. This is explained in terms of the
      arousal effect of loud auditory stimuli.

PMID- 8153245
TI  - A probabilistic multidimensional model of location information.
AB  - A probabilistic multidimensional model of location discrimination is developed
      and applied to data from an experiment in which subjects are required to
      determine whether a briefly presented horizontal and vertical bar are touching.
      The proposed gap-detection model assumes that errors in perception are due to
      variability in the perceived location and/or in the perceived length of the bars.
      A series of gap-detection models that allow variability only in perceived
      location were rejected on the basis of likelihood-ratio tests of overall goodness
      of fit. However, when the models were modified to account for: (a) a compression
      of the distance perceived between the bars (Wolford, 1975), or (b) the bisection
      illusion (Kunnapas, 1955), excellent absolute fits to the data were obtained. A
      pair of models that suggests that the horizontal/vertical illusion or a response
      bias was operative failed. Applications of the model to more conventional object
      perception experiments (e.g., the illusory-conjunction experiment) are discussed.

PMID- 8153246
TI  - Conflict between aftereffects of retinal sweep and looming motion.
AB  - Observers looked monocularly into a tunnel, with gratings on the left and right
      sides drifting toward the head. An exposure period was followed by a test with
      fixed gratings. With fixation points, left and right retinal fields could be
      stimulated selectively. When exposure and test were on the same retinal fields,
      but fixation was on opposite sides of the tunnel during exposure and test
      periods, aftereffects of retinal sweep and of perceived looming were in opposite
      directions. The two effects tended to cancel, yielding no perceived aftereffect.
      When they did occur, aftereffects in the retinal and the looming directions were
      equally likely. Cancellation was significantly more likely in the experimental
      conditions than in the control, when fixation always remained on the same side.
      When areas of retinal stimulation in the exposure and test periods did not
      overlap, cancellation was less frequent and aftereffects of looming were more
      frequent. Results were not significantly different for left and right visual
      fields, indicating that cortical vs. subcortical OKN pathways do not influence
      the illusion. Vection resulted for 16 of 20 observers under one or another of our
      conditions.

PMID- 8153248
TI  - Social neuroscience: autonomic, neuroendocrine, and immune responses to stress.
AB  - The immune system is influenced by central nervous system processes that are
      shaped by social and psychological factors. Considerations of social factors,
      intrapersonal process, and autonomic psychophysiology therefore may contribute to
      a fuller understanding of both immune and brain function. Research reviewed here
      (a) examines the socioemotional factors that contribute to, or moderate,
      responses to brief and chronic stressors, (b) determines whether or not stable
      individual differences in heart rate reactivity predict neuroendocrine and immune
      responses to a brief psychological stressor and to an influenza virus vaccine,
      and (c) investigates the autonomic origins of individual differences in low and
      high heart rate reactivity and their relationship to neuroendocrine and immune
      responses to chronic and acute stressors. Among our findings are: (a) acute
      psychological stressors activate the sympathetic adrenomedullary system across
      individuals and affect immune function; and (b) individuals characterized by high
      sympathetic cardiac reactivity to acute psychological stressors also show a
      relative activation of the hypothalamic pituitary adrenocortical system and
      altered immune function.

PMID- 8153247
TI  - Attentional zooming and the global-dominance phenomenon: effects of level
      specific cueing and abrupt visual onset.
AB  - In four experiments level-specific cueing of hierarchically structured stimuli
      was used to test the hypothesis that valid cues can reduce the global-dominance
      phenomenon. Compound stimuli (Experiments 1 and 2) or simple geometric forms
      (Experiments 3 and 4) were presented with different SOAs after a valid, an
      invalid, or a neutral level-specific cue (cue validity 80%). Costs for invalid
      cues and benefits for valid cues were produced in all experiments. However, a
      reduction of the global-local RT difference to about zero was achieved only after
      the reduction of the abrupt visual onset accompanying stimulus presentation in
      Experiments 2 (with compound stimuli) and 4 (with simple geometric forms). In
      addition, there was no longer the typical asymmetric-interference pattern (i.e.,
      features of the global level interfere with local identification, but not vice
      versa) that was one of Navon's (1977) main arguments for assuming a perceptual
      precedence. It is concluded that the RT that is longer for local than for global
      identifications is produced by the time needed to refocus visual attention
      intentionally from the global level, which is focussed at first unintentionally,
      to the local level.

PMID- 8153249
TI  - Is a stimulus conveying task-relevant information a sufficient condition to
      elicit a stimulus-preceding negativity?
AB  - Movement-preceding and stimulus-preceding negativities were recorded when a
      movement was followed by one of three informative visual stimuli. The meaning of
      the visual stimulus alternated between (a) conveying a task-relevant instruction
      about a subsequent time production task and (b) providing feedback (knowledge of
      results) about performance on the current time production task. In a control
      condition, premovement and postmovement scalp potentials were recorded when
      subjects made the same movements but in a voluntary, self-paced manner. Under all
      conditions, movements were preceded by a movement-preceding negativity, and
      neither the amplitude nor the lateral asymmetry of this negativity was affected
      by the subsequent presentation of either kind of informative stimulus. When the
      movement was followed by a stimulus conveying knowledge of results, the
      negativity in the postmovement epoch was enhanced, but this enhancement was not
      evident in epochs preceding instruction stimuli. We conclude that not all task
      relevant stimuli elicit a stimulus-preceding negativity, and we provide a
      functional interpretation of this negativity in terms of emotional anticipation
      and the contingency of the stimulus on a previous event.

PMID- 8153250
TI  - Visual spatial attention to stimuli presented on the vertical and horizontal
      meridian: an ERP study.
AB  - In the first experiment, 48 subjects carried out a visual spatial attention task.
      Stimuli were presented at the vertical meridian, either above or below a fixation
      dot, and the subjects were instructed to attend to one of these stimulus
      positions and ignore the other position. In three different conditions, the
      distances between stimulus positions and fixation were 0.5 degrees, 0.9 degrees,
      and 1.3 degrees. Subjects searched for the presence of prememorized target
      letters at the attended location: memory load was one or four items in different
      conditions. The P1/N1 enhancement typically found on the horizontal dimension was
      not observed on the vertical dimension. Instead, a positive shift of the attended
      compared with the unattended stimuli was found, which was most prominent at
      anterior electrodes. This positivity showed effects of the distance manipulation.
      The N2b-P3a effects of attention and the effect of memory load (search
      negativity) normally present in this kind of selective search task were also
      found. Reaction times were faster when attention was directed above fixation than
      when it was directed below fixation. The event-related potential data suggested
      that this difference could be attributed to a more efficient neglecting of
      irrelevant stimuli presented below fixation. In Experiment 2, we examined whether
      the absence of the P1/N1 enhancement as the result of spatial attention in
      Experiment 1 could be attributed to (a) the presentation of stimuli along the
      vertical meridian instead of along the horizontal meridian, (b) the use of
      midline electrodes instead of lateralized electrodes, and (c) the relatively
      small spatial separation between the relevant and irrelevant stimuli. Twelve
      subjects searched for the presence of a single target letter at an attended
      position in three different conditions. In two of the conditions the letters were
      presented to the left or right of fixation. The distance between fixation and the
      stimulus positions was 1.3 degrees in one of these conditions and 3 degrees in
      the other condition. In the third condition, the stimuli were presented at 3
      degrees above or below fixation. In all three conditions effects similar to those
      in Experiment 1 were observed. In addition, in all three conditions an
      enhancement of the P1 and N1 components was found at two lateral occipitotemporal
      electrodes.

PMID- 8153251
TI  - An ERP study on visual spatial priming with peripheral onsets.
AB  - Visual event-related potentials were measured for peripheral target stimuli that
      were preceded by a peripheral square. Targets appeared either at the same
      location as the square or in the opposite visual hemifield. In Experiment 1, 75%
      of the trials were same-location trials, and in Experiment 2, same- and opposite
      location trials were equiprobable. The subject's overt response was dependent
      either on the identity or on the location of the target. In both experiments,
      opposite-location targets elicited an enhanced P1 at posterior electrodes
      ipsilateral to the position of the letter. This enhancement may be due to a
      sensory inhibition of same-location targets. Same-location targets elicited an
      enhanced negativity between 130 and 300 ms, with a first peak located parietally
      and a second peak broadly distributed over midline electrodes. This effect was
      larger in Experiment 1 than in Experiment 2 and is interpreted as enhanced
      processing of same-location targets due to an attentional orienting process
      elicited by the peripheral square.

PMID- 8153252
TI  - Heart rate and sustained attention during childhood: age changes in anticipatory
      heart rate, primary bradycardia, and respiratory sinus arrhythmia.
AB  - This study examined age changes in three aspects of heart rate responsivity
      elicited in an auditory oddball task; anticipatory heart rate change, primary
      bradycardia, and respiratory sinus arrhythmia. Three age groups (5-, 7-, and 9
      year-old boys) were presented with series of target (15%) and standard (85%)
      tones. The results were consistent with the findings reported previously in the
      adult literature. Heart rate decreased in anticipation of the target tone. The
      morphology of anticipatory deceleration was somewhat different for the 5-year
      olds compared to the older children. Stimuli presented during the early part of
      the cardiac cycle induced added deceleration, but this primary bradycardia did
      not differ between age groups. Respiratory sinus arrhythmia did not discriminate
      between age groups but was suppressed during the performance of the oddball task
      relative to base level. It was concluded that these three aspects of heart rate
      responsivity show developmental constancy rather than change.

PMID- 8153253
TI  - An event-related potential study of sensory representations of unfamiliar tonal
      patterns.
AB  - Tonal patterns were delivered to 17 subjects instructed to read a self-selected
      book and to ignore the auditory stimuli. The standard pattern contained eight 50
      ms segments differing in frequency. Infrequent changes of single segments within
      the pattern elicited negative modulations of the event-related brain potentials
      (ERPs) as compared with the ERPs elicited by the standard pattern. The change
      consisted of either a duplication of a single segment or an interchange of two
      segments within the pattern. Because of the nature of the change, the ERP
      modulation cannot be explained by a simple refractoriness mechanism or by
      assuming that the mechanism generating the negative modulation relies on
      representations of only the spectral but not the temporal information of the
      pattern. Therefore, the spectral and the temporal information of the tonal
      patterns were represented by the information processing system on a grain of
      single segments.

PMID- 8153254
TI  - Ontogenetic variations in auditory arousal threshold during sleep.
AB  - Developmental variations in auditory arousal thresholds during sleep were
      investigated in four groups of normal male subjects--children, preadolescents,
      adolescents, and young adults. Arousal thresholds were determined during NREM and
      REM sleep for tones presented via earphone insert on a single night following two
      adaptation nights of undisturbed sleep. Age-related relationships were observed
      for both awakening frequency and stimulus intensity required to effect awakening,
      with awakenings occurring more frequently in response to lower stimulus
      intensities with increasing age. Although stimulus intensities required for
      awakening were high and statistically equivalent across sleep stages in
      nonadults, higher intensity stimuli were required in Stage 4 relative to Stage 2
      and REM sleep in adults. These results confirm previous observations of marked
      resistance to awakening during sleep in preadolescent children and suggest that
      processes underlying awakening from sleep undergo systematic modification during
      ontogenetic development.

PMID- 8153255
TI  - Muscle tension in generalized anxiety disorder: elevated muscle tonus or agitated
      movement?
AB  - The purpose of this study was to investigate the amplitude characteristics of
      frontalis and gastrocnemius electromyographic (EMG) activity in clinically
      anxious and nonanxious populations. Eighteen women with generalized anxiety
      disorder (GAD) and 19 nonanxious women were compared during baseline, laboratory
      stressor, and recovery conditions. EMG mean levels were greater for the GAD
      group, but there were no group differences in EMG skewness. During the stressor
      the GAD group had a significant reduction in frontalis EMG variability.
      Gastrocnemius muscle activity for both groups during the stressor condition
      increased in mean levels and variability while decreasing in skewness. These
      results indicate that clinically anxious individuals have elevated muscular tonus
      and have reduced variability in frontalis activity during stressful tasks. Also,
      the gastrocnemius muscle exhibited a stressor reactivity, whereas the frontalis
      did not. This study presents an approach to EMG analysis that could be useful in
      distinguishing unique features of anxiety as well as other emotional disorders.

PMID- 8153256
TI  - The relationship of sweat gland count to electrodermal activity.
AB  - This study assessed whether greater skin conductance activity at the distal
      versus medial site (Scerbo, Freedman, Raine, Dawson, & Venables, 1992) is
      attributable to a greater number of active (open) sweat glands at the distal
      site. The number of sweat glands was measured using the Palmar Sweat Index (PSI).
      Twenty-four subjects were exposed to 10 auditory stimuli. Electrodes were placed
      on the fore and middle fingers of each hand, using distal sites on one hand and
      medial sites on the other. The PSI was measured at the medial and distal
      phalanges adjacent to the electrode placement sites. The distal site contained
      more open and total sweat glands. Open gland count had the strongest correlations
      with skin conductance. Multivariate analyses of covariance revealed that site
      effects for nonspecific and orienting response frequency and trials to
      habituation were associated with site differences in open glands. Skin
      conductance measures and the PSI reveal greater electrodermal activity at the
      distal site. In addition, the number of open glands may be a useful measure
      related to electrodermal response frequency when polygraph measurement is
      unavailable.

PMID- 8153257
TI  - Signal attenuation as a function of integrator time constant and signal duration.
AB  - In some laboratories, eyeblink electromyogram is rectified and smoothed before
      the analog signal is digitized. The relationship among the integrator time
      constant, the duration of the response, and the attenuation of the data was
      investigated by passing a number of signals at durations of 5, 10, 20, 50, and
      100 ms into a contour-following integrator (Coulbourn model S76-01), which first
      rectifies and then smooths (integrates) the signal. Integrator time constants of
      10, 42, 70, 144, and 300 ms were used. The output of the integrator was sampled
      (1,000 Hz) and stored on a Macintosh SE computer. The integrator attenuated the
      signal, and the amount of attenuation increased as the duration of the signal
      decreased and as the time constant of the integrator increased. For brief inputs,
      the integrator does not charge fully, so only the early portion of the charge
      limb is present, and this early portion is the steepest part of the charge limb.
      Therefore, the longer the time constant, the less likely that small or brief
      responses will be detected.

PMID- 8153258
TI  - Origins of baseline variance and the Law of Initial Values.
AB  - The Law of Initial Value (LIV) asserts that the magnitude of a phasic
      psychophysiological response is dependent on the initial baseline level. Although
      results in accord with the LIV are often observed, exceptions are frequent,
      especially for between-subjects analyses. A general assumption in studies of the
      LIV is that a given baseline difference is equivalent regardless of its
      functional origin. The present study examined the relationships between basal
      heart period variance, arising from alternate sources, and the magnitude of the
      chronotropic response to a speech stressor. Results reveal that baseline
      differences due to orthostatic manipulations, which are known to be largely of
      autonomic origin, yielded larger LIV effects than did individual differences in
      basal heart period, which include a significant nonautonomic component. The
      minimal LIV-like effects of baseline differences associated with non-autonomic
      factors, relative to variations in autonomic control, may contribute to the
      inconsistent appearance of between-subjects LIV effects.

PMID- 8153259
TI  - Feasibility of intracranial near-infrared optical scanning.
AB  - Light injected at a point on a surface of a scattering medium is emitted at the
      surface after traveling a quasisemicircular path deep into the medium. This
      phenomenon can be exploited to detect objects immersed in the medium from time
      resolved measurements of light intensity at the surface. Our experiments on model
      systems demonstrate that absorbing objects, surrounded by bone and other
      scattering material, can be detected. The technique yields surface images of
      absorbing objects submerged in a scattering medium. Images of the same phantoms
      inside the cavity of a skull can be obtained by the same technique.

PMID- 8153260
TI  - [Translation and commentary of the Hippocrates treatise 'The illness of girls'].
AB  - De Virginibus traditionally belongs to Cnidian gynecologic treatises. The
      comparison with De Mulieribus shows a great difference in the physiology of
      menstruation and its diseases. The author, by explaining intelligence by the
      participation of heart and blood, is far from De Morbo sacro and draws near to
      Aristole's conceptions. Moreover, its vocabulary and rhetoric style indicate that
      this fragment can be attributed to a physician of Aristotle's period or later.

PMID- 8153261
TI  - The body republic: social order and human body in Renaissance medical thought.
AB  - The representation of the human body built by medicine had historical references
      and analogical relations with other compounds of the culture of each particular
      period. The organic model, the coordinated and hierarchical dependence of the
      body parts, its subordination to a prevailing element (the brain or the heart,
      depending on the authors and times) guided directly by a soul infused by God...
      These are some of the aspects which reflect the relation between the image of the
      body and the justification of the ideological and social order, as a natural one.
      Among the numerous sources of Renaissance medicine that could bring significant
      facts about this theme, the present work is based on anatomical treatises and
      books of natural philosophy like those written by Bernardino Montana de
      Monserrate, Alonso de Fuentes, Realdo Colombo, Hieronimus Montaltus, Andrea
      Cesalpino and Miguel Sabuco, all of whom are good exponents of Renaissance
      anatomy and physiological thought.

PMID- 8153262
TI  - [Uprising in the faculty. On the rhetorical function of 'therapeutic nihilism' in
      traditional medicine in Vienna].
AB  - It has been a long tradition to quote from Joseph Dietl's 'manifesto' of
      therapeutic nihilism from 1845 to illustrate the perils of medical extremism. But
      Dietl's claim for medicine as a natural science cannot fully be understood
      without considering the social and political circumstances the developing New
      Vienna School had to face. The professionalization of Viennese academic medicine
      was opposed by the forces of restaurative absolutism and, in particular, the
      traditional preponderance of medical practitioners who played a major role in the
      medical faculty.

PMID- 8153263
TI  - [Eugenics and public health: legal sterilization of mentally ill in the Vaud
      canton (Switzerland)].
AB  - In 1928 the canton of Vaud (Switzerland) voted a bill which legalized eugenics
      sterilization. The sterilization of the mentally ill was a public-health measure
      among others. It fitted in a wide variety of policies whose aims were to increase
      the physical and psychical well-being of the population. Vaud eugenics was
      progressive, reformist and non-partisan. This paper examines the intellectual,
      social and political conditions of the 1928 bill.

PMID- 8153264
TI  - Inducers and 'organizers': Hans Spemann and experimental embryology.

PMID- 8153265
TI  - A community project to encourage compliance with mental health treatment
      aftercare.
AB  - Rehospitalization of mentally ill persons has been associated mainly with two
      major factors, noncompliance with the prescribed course of medication and
      noncompliance with planned aftercare. The authors developed and pilot tested a
      community health project designed to assist chronically ill mental health
      patients who, when discharged from hospital care, are considered at high risk for
      rehospitalization. The project was designed to support clients' efforts to comply
      with their prescribed course of aftercare therapy, support, and medication. The
      project was developed at the University of Maryland at Baltimore, School of
      Nursing, in cooperation with the U.S. Department of Veterans Affairs. The project
      consisted of interventions during the critical time after hospital discharge but
      before the client becomes fully established in outpatient treatment. The
      interventions were based on the principle of catching the high-risk client before
      a crisis situation occurred. The four interventions were (a) discharge planning
      for the individual client that stressed education about the client's psychiatric
      illness; (b) education about medications prescribed for the client; (c) an
      education program for family members and others to assist them in helping the
      individual client; and (d) communicating with the client to reinforce the support
      network concept, using a 48-hour followup telephone call, an information contact
      by post-card, and a non crisis telephone line. The project was implemented on a
      pilot basis during the fall of 1992 by the nursing students and staff members at
      a major urban Department of Veterans Affairs Medical Center (VAMC). The pilot
      project involved 31 staff and community health professionals and 68 client
      interactions during 1992. Data were collected from clients and staff members
      during and after the project was implemented. The project was evaluated using a
      multimethod evaluation tool, and revisions were incorporated based on the
      results.Clients who participated in the program indicated that establishing
      caring relationships within a support network was the most significant factor in
      achieving compliance with aftercare. The results of the project, noted by staff
      members and observers, have led to implementation and expansion of interventions
      by subsequent groups of nursing students. Plans for the future of the project
      include determining rates of recidivism and obtaining more information on other
      health outcomes of clients.

PMID- 8153266
TI  - A peer education program to promote the use of conflict resolution skills among
      at-risk school age males.
AB  - Violence is devastating the lives of children in America's major cities. The
      problem of violence is particularly acute among disadvantaged young urban males.
      This program focuses on violence prevention in school-age boys using creative
      educational techniques and community partnership. The goal of this school-based
      program is to decrease the incidence of violent episodes in the school by
      teaching conflict resolution skills. Conflict resolution skills are taught in the
      health education component of the school health program. Skills are taught using
      a peer education model supervised by the school health nurse and planned in
      partnership with a Violence Prevention Advisory Board. Peer education teams
      consisting of fifth and sixth grade boys are trained and serve as peer educators
      for the boys in grades K-4. The violence prevention peer education program
      stresses primary prevention and targets at-risk school age males. The proposal
      uses a model that promotes the development of student leadership skills and self
      esteem. The proposal suggests ways to promote school and community involvement
      using an advisory board made up of student, community, and school leaders. The
      peer education program is cost effective and demonstrates how existing resources
      can be used creatively within the school setting.

PMID- 8153267
TI  - The AIDS prevention magic show: avoiding the tragic with magic.
AB  - Teenagers are a crucial target group for interventions concerning acquired
      immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV).
      Experimenting with their burgeoning sexuality and increased ability to obtain
      drugs, they are prime candidates for AIDS prevention and education strategies.
      The intervention described in this paper is a 30-minute magic show, presented by
      Cyrus (or Iris) the Virus, a sinister but entertaining character portrayed by any
      health educator willing to spend a few hours learning the magic tricks. The
      tricks explain why sharing needles and choosing sexual partners based on
      appearance alone can result in AIDS. Cyrus also uses magic to communicate the
      ways that AIDS is not transmitted, how to refuse sex, and how to use condoms
      correctly. The show, as well as increasing the audience's knowledge about HIV,
      attempts to induce behavioral change by increasing participants' perceived self
      efficacy--a predictor of healthful behavior. Still in its pilot phase, the show
      has been seen by 281 students ages 10-15 years. Viewers rate the show highly, and
      preliminary analysis suggests that perceived self-efficacy has been significantly
      improved.

PMID- 8153268
TI  - Developing health education materials for inner-city low literacy parents.
AB  - The question of identifying and treating childhood illness confronts all new
      parents. Misconceptions often lead parents to manage illnesses in their young
      children inappropriately through overly aggressive treatment or insufficient
      attention. This responsibility is especially challenging for low-income new
      parents who lack the literacy levels needed to understand and use much of the
      existing health education literature and who are without access to health
      facilities and providers. In response to a perceived need for health information
      directed at low-income, low-literacy parents, students from the University of
      California at Los Angeles School of Public Health created an easy-to-use
      reference booklet called "A Parent's Guide: When Your Child Is Sick." The
      booklet's aim is to assist parents in treating common childhood illness and
      identifying more serious diseases requiring medical attention. A comprehensive
      and manageable amount of information is provided in the booklet. Behaviors and
      issues covered include (a) recognition of symptoms, (b) actions that could be
      taken in the home, (c) medicines that could be administered, and (d)
      recommendations on how persistent problems might be handled.

PMID- 8153269
TI  - Assessing prevention effectiveness using data to drive program decisions.
AB  - The measure of the effectiveness of health promotion and disease prevention
      activities is the impact of prevention policies, programs, and practices on
      public health and clinical medicine. Assessing prevention effectiveness involves
      continuing quantitative analysis of health outcomes resulting from prevention
      practices. Additionally, assessment involves evaluation of disease- and injury
      prevention activities, including their medical, legal, ethical, and economic
      impacts. Although assessing the effectiveness of prevention activities involves
      measuring efficacy, safety, and cost, the primary criterion is to improve health
      at a reasonable cost, not merely to contain costs. Policy makers can use the
      results of assessments to set priorities in public health. The authors use case
      studies to illustrate various approaches to evaluating prevention programs,
      including programs for preventing measles, breast cancer, and diabetic
      retinopathy. Rigorous evaluation of the effectiveness of prevention activities is
      essential to the wide acceptance of preventive interventions and the willingness
      to pay for them.

PMID- 8153270
TI  - Estimated savings in U.S. dental expenditures, 1979-89.
AB  - The American public saved more than $39 billion (1990 dollars) in dental
      expenditures from 1979 through 1989 in contrast to the substantial increases in
      expenditures in other sectors of the U.S. health care system that have pushed the
      system to the brink of major reform. The dental savings were estimated after
      controlling for the influence of economic factors, such as changes in prices,
      insurance, and income, as well as noneconomic factors that could influence the
      extent of dental disease in the U.S. population. Results of the analysis confirm
      the importance of both economic and noneconomic factors in the determination of
      the savings in dental expenditures.

PMID- 8153271
TI  - Applications of data from the CDC Family of Surveys.
AB  - The CDC Family of Surveys is a national serologic surveillance system set up to
      characterize the extent of human immunodeficiency virus (HIV) infection in the
      United States. The now Centers for Disease Control and Prevention (CDC) and
      participating State and local health departments began the system in 1987. HIV
      seroprevalence data are collected by unlinked (anonymous) surveys of particular
      components of the population that include childbearing women; clients of sexually
      transmitted disease clinics; injecting drug users; tuberculosis patients; and
      several special populations, such as adolescents, prisoners, and homeless
      persons. The data obtained have been used extensively on both national and local
      levels to assist HIV-prevention programs. Data from the surveys have been used to
      identify specific demographic groups at risk for HIV infection so that health
      education programs may be planned and made available to them in clinical
      settings. Local serosurvey results have been used in planning and implementing
      prevention programs and in planning health services for HIV-positive persons. The
      completeness, or coverage, of HIV counseling and testing programs has been
      evaluated by comparing seroprevalences among clients tested voluntarily with
      those tested in the unlinked survey. Survey data are used in formulating
      recommendations and standards of care for health practitioners, in allocating
      resources, and in carrying out long-range planning for HIV prevention and
      treatment services for at-risk groups. Such data are essential to the decision
      making process in forming public health policy and recommending practices
      involving the HIV epidemic.

PMID- 8153272
TI  - Admissions of injection drug users to drug abuse treatment following HIV
      counseling and testing.
AB  - The outcomes of counseling and testing programs related to human immunodeficiency
      virus (HIV) infection and risk of infection among injection drug users (IDUs) are
      not well known or understood. A counseling and testing outcome of potential
      public health importance is attaining admission to drug abuse treatment by those
      IDUs who are either infected or who are at high risk of becoming infected. The
      authors investigated factors related to admission to drug abuse treatment among
      519 IDUs who received HIV counseling and testing from September 1987 through
      December 1990 at a men's prison and at community-based testing sites in
      Worcester, MA. By June 1991, 123 of the 519 IDUs (24 percent) had been admitted
      to treatment. Variables associated with their admission included a long history
      of drug injection, frequent recent drug injection, cleaning injection equipment
      using bleach, prior drug treatment, and a positive HIV test result. Logistic
      regression analyses, controlling for effects of recruitment site, year, sex, and
      area of residence, generally confirmed the associations. IDUs in the study
      population who were HIV-infected sought treatment or were admitted to treatment
      more frequently than those who were not infected. The results indicate that
      access to drug abuse treatment should be facilitated for high-risk IDUs and for
      those who have begun to inject drugs recently.

PMID- 8153273
TI  - The health effects of ionizing radiation: a survey of local health officials in
      New England and New York.
AB  - The purpose of the study is to determine the educational needs of public health
      officials concerning their knowledge, attitude, beliefs, and practices with
      specific reference to ionizing radiation. The public health directors or
      designates, working in health departments whose jurisdictions fall within a 60
      mile radius of the 14 operating nuclear power plants in the New York-New England
      region, were studied. A review of the literature indicates that historically
      there appears to have been a limited effort to conduct such a needs assessment in
      the United States. A questionnaire was developed to measure the public health
      directors' knowledge, attitudes, and practice. The instrument was mailed in the
      summer of 1992 to all public officials listed in the National Directory of Local
      Health Departments. Knowledge, attitude, and practice questions were analyzed in
      terms of frequency of correct, incorrect, and don't know responses. The data
      presented convey the message that there should be public input into the risk
      assessment of nuclear plants and that local health departments should inform the
      public about the health risks posed by nuclear plants in their locality. The
      authors recommend that an appropriate Federal agency sponsor a national survey
      and that States should establish a training program on the health effects of
      ionizing radiation for local public health officials.

PMID- 8153274
TI  - Prevalence of medical technology assistance among children in Massachusetts in
      1987 and 1990.
AB  - In 1987 and 1990 in Massachusetts, surveys were conducted to determine the size,
      pattern of distribution, and trends in the population of children assisted by
      medical technology. The authors obtained an unduplicated count of all
      Massachusetts children from 3 months to 18 years of age who used one or more of
      the following: tracheostomy, respirator, oxygen, suctioning, gastrostomy, jejunal
      or nasogastric feedings, ostomies, urethral catheterization, ureteral diversion,
      intravenous access, or dialysis. By comparing counts obtained from medical and
      educational sources, the authors were able to perform a capture-recapture
      analysis to estimate the overall number of children dependent upon these
      technologies. The number of children identified in our surveys increased from
      1,085 in 1987 to 1,540 in 1990. However, the capture-recapture analysis yielded
      estimates of 2,147 plus or minus 230 for 1987 and 2,237 plus or minus 131 for
      1990. This suggests that the population of children dependent upon medical
      technology was essentially stable during this period, and that the 42 percent
      increase in the number of children identified in our survey reflected improved
      sampling techniques. During the 3 years, shifts in the pattern of technology use
      were noted, however. Use of oxygen and gastrostomy increased, and urostomy use
      declined. A change in the age distribution of the children was also documented,
      with a shift in the preponderence of technology use from 12 to 24 months in 1987
      to children in the first year of life in 1990. Using the 1990 estimate and the
      1990 U.S. census figures, an overall prevalence estimate of 0.16 percent was
      calculated. Applying this to the U.S.child population yields an estimate of
      101,800 children assisted by medical technology nationwide(assuming comparable
      technology use in other States). This information will facilitate policy analysis
      and program planning on regional and national levels for this medically complex
      group of children.

PMID- 8153275
TI  - Substance dependent American Indian veterans: a national evaluation.
AB  - Demographic, clinical, and treatment episode characteristics of 3,087 American
      Indian veterans discharged from Department of Veterans Affairs hospitals in
      fiscal year 1991 were examined. Substance use disorders were diagnosed in 46.3
      percent of discharged American Indians, compared with 23.4 percent of discharged
      veterans overall. More than 97 percent of American Indian substance use diagnoses
      were for alcohol dependence, while rates of other drug use disorders were low.
      Substance dependent American Indians were younger, and more likely to be male and
      unmarried, than nondependent American Indians. Psychiatric disorders,
      particularly personality disorders, depression, and posttraumatic stress
      disorders, were more prevalent among American Indians diagnosed with substance
      use disorders, than among nondependent American Indians. American Indians with
      substance use disorders were similar demographically to the general population of
      substance dependent veterans. Rates of diagnosed psychiatric disorders and drug
      dependencies other than alcohol were lower among American Indians receiving
      substance (alcohol or drug) use diagnoses than among the general population of
      substance dependent veterans. Rates of rehospitalization following discharge were
      higher in substance-abusing American Indian veterans than among their
      counterparts. Potential explanations for these findings are discussed.

PMID- 8153276
TI  - The urban American Indian oversample in the 1988 National Maternal and Infant
      Health Survey.
AB  - Although more than two-thirds of American Indians and Alaska Natives (AI) live
      outside reservations and Tribal lands, few data sets describe social and maternal
      child health risk factors among urban AI. The Indian Health Service sponsored a
      special effort to survey mothers of AI infants as part of the 1988 National
      Maternal and Infant Health Survey (NMIHS), a comprehensive national study
      conducted by the National Center for Health Statistics, Centers for Disease
      Control. The authors analyzed questionnaires completed by mothers residing in
      selected locations served by urban Indian health programs and compared the data
      with those for women of other races residing in metropolitan areas. After
      adjusting the sample for non participating States, the response rate in the Urban
      Indian Over sample was 60.8 percent (763 of 1,254). More than 45 percent of AI
      and black respondents, compared with 15 percent of white respondents, reported an
      annual household income of less than $10,000. About half of AI and black women,
      compared with nearly three-quarters of white women, reported having insurance or
      health maintenance organization coverage during pregnancy. Despite having a
      similarly low rate of health insurance coverage and low household income, AI
      respondents were far less likely than black respondents to have Medicaid
      coverage. A higher proportion of AI women than of black or white women reported
      difficulties in obtaining prenatal care, and AI women were less likely to obtain
      prenatal care. AI women were also less likely than white women to obtain prenatal
      care in the first trimester. Although a similar proportion of Al and white women
      reported that they consumed alcohol during the year before pregnancy, a higher
      proportion of Al drinkers than of white drinkers reported consuming one or more
      drinks weekly after finding out they were pregnant. The proportion of unwanted
      pregnancies was higher among Al women than among white women, but lower than
      among black women. Al and black women had a higher prevalence of depressive
      symptoms than did white women.The data suggest that urban Al mothers experience a
      disproportionate burden of economic, social, and behavioral risk factors for
      adverse pregnancy outcome.In spite of some data limitations, the Urban Indian
      Over sample of the NMIHS provides important information about social and health
      risk factors among urban Al mothers.

PMID- 8153277
TI  - Mental disorders in primary care services: an update.
AB  - Frank mental disorders, such as depression and panic disorder, are prevalent in
      primary care; they cause people substantial suffering and interfere with daily
      functioning. Even subthreshold or "subsyndromal" conditions, with fewer symptoms
      than necessary for making a diagnosis, cause substantial morbidity. Recent
      literature on mental disorders in primary care, where many, if not most, people
      with mental health problems are seen, is reviewed with focus on recognition and
      diagnosis issues, management of these problems in primary care, obstacles to
      accurate diagnosis and appropriate treatment, and prevention issues. In addition
      to a review of recent research, there is an effort to place these topics in the
      context of various directives, including research and Federal documents, that
      have direct implications for better treatment in primary care of people with
      mental disorders (for example, practice guidelines). Mental health problems and
      disorders seen in primary care are a public health problem meriting immediate
      attention and substantial work at many levels--clinical, educational,
      organizational, and budgetary.

PMID- 8153278
TI  - Tuberculosis prevention practices and perspectives of physicians in DeKalb
      County, GA.
AB  - Knowing the reasons some physicians do not adhere to the disease prevention and
      treatment recommendations of expert committees can assist in the development of
      future recommendations more likely to be adopted by physicians. The authors
      describe the attitudes and practices of physicians relative to tuberculosis
      prevention in DeKalb County, GA. Tuberculosis is an important problem in the
      county, which includes part of the City of Atlanta, as well as suburban areas.
      Questionnaires for anonymous reply were mailed to 1,621 physicians in the county
      in 1991, and 848 (53 percent) were completed and returned. The final sample was
      793 physicians, who were grouped into 5 specialty areas. Primary care physicians
      were the group most commonly involved in specific tuberculosis screening and
      prevention activities. Medical and pediatric specialists, surgeons, obstetricians
      gynecologists, and other physicians were significantly less likely to be involved
      in such activities. Given that primary care physicians constitute a decreasing
      proportion of physicians in the United States, the findings suggest the
      importance of ensuring that future strategies for tuberculosis prevention take
      into account the increasingly specialized nature of the medical practice
      environment.

PMID- 8153279
TI  - Self-reported awareness of the presence of product warning messages and signs by
      Hispanics in San Francisco.
AB  - This study investigated the self-reported awareness of the presence of product
      warning messages and signs among random samples of Hispanics in San Francisco
      surveyed in 1990 and in 1991. The messages that were tested related to
      cigarettes, alcoholic beverages, and other consumer products. A random sample of
      1,204 Hispanics (43.5 percent males) were interviewed by telephone in 1990. The
      corresponding figure for the second survey in 1991 was 1,569 Hispanics (41.1
      percent males). In general, respondents reported low levels of awareness of the
      presence of product warning messages and signs. The exception was warning
      messages on cigarette packets which approximately 70 percent of the respondents
      reported having seen within the 12 months before the survey. There was an
      increase from 1990 to 1991 in the reported awareness of warning messages for
      wine, beer, and cigarettes. Smokers and drinkers of alcoholic beverages reported
      the highest levels of awareness of the relevant warning messages and signs.
      Length of exposure to warning messages and multiplicity of sources (for example,
      advertisements and products) seem to produce greater levels of awareness of the
      presence of product warning messages. Less acculturated, Spanish-speaking
      Hispanics are less likely to report being aware of the warnings, particularly
      those that appear only in English (for example, alcoholic beverages).

PMID- 8153280
TI  - Public health and the media in California: a survey of local health officers.
AB  - Increasingly, public health interventions are dependent on effective health
      communications. There are, however, few data examining the relationship and
      interactions between local public health officers and representatives of the
      media in the literature. This study sought to collect data on the quality and
      quantity of interactions between California's 62 local health officers and the
      media. A survey form was sent to the health officers representing all 58 county
      and four city health departments in the State of California to assess the extent
      of media interaction, the existence of institutional media policies, the
      professional and personal character of media relations, the perceived accuracy of
      media reporting, use of the media for health education and advocacy, the
      availability of training in media relations for staff members, and whether media
      interaction facilitated or impeded achievement of public health objectives.
      Differences in responses according to the population of the political
      jurisdiction also were assessed. With 87 percent of the health officers
      responding, 51 percent reported 10 years or more experience interacting with the
      media; 65 percent said they dealt with the print media mostly on a daily, twice
      weekly, or weekly basis. In only 19 jurisdictions were there written policies on
      media relations, but in 43, media releases undergo a pre-release review. Most
      health officers characterized media relations as reactive, and 80 percent said
      they were appropriate and had an educational impact. Media interactions were
      largely believed to be of benefit to the public and were not generally perceived
      as adversarial. Health officers were of the opinion that media representatives
      could become more technically and scientifically knowledgeable on public health
      issues but also indicated that they or their own public health staff would
      benefit from continuing education on managing media relations. Eighty-six percent
      stated that the media strongly or moderately facilitate the achievement of public
      health objectives. Further study of this important component of public health
      practice is warranted.

PMID- 8153281
TI  - Activities associated with drownings in Imperial County, CA, 1980-90:
      implications for prevention.
AB  - Statewide surveillance in California determined that the highest drowning rate
      from 1980 through 1989 was for the rural, desert county of Imperial (21.9
      drownings per 100,000 population). To identify activities associated with
      drowning in this county, the authors abstracted data from the county sheriff
      coroner's reports. From 1980 through 1990, there were 317 unintentional
      drownings; 85 percent occurred in irrigation canals. The activity prior to
      drowning was known for 262 persons (83 percent), and the most common activity was
      illegal entry into the United States. Overall, 140 persons (53 percent) were
      illegal entrants. Ninety-three percent of illegal entrants drowned in the All
      American Canal; the monthly drowning rate increased as the monthly average water
      velocity in the canal increased (r = 0.36; P < 0.001). Forty-eight persons (18
      percent) drowned while riding in or on a land vehicle (automobile, pick-up truck,
      motorcycle, dune buggy, or tractor), the second most common activity associated
      with drowning. Seventy percent of the 23 drivers had an alcohol concentration of
      100 milligrams per deciliter or more, California's limit for intoxication. To
      reduce drownings in Imperial County, prevention strategies should target persons
      engaged in at-risk activities near bodies of water. These strategies should
      include the identification and use of effective canal safety devices.

PMID- 8153282
TI  - Rates of bicycle helmet use in an affluent Michigan County.
AB  - Bicycle helmet use in the United States has remained low despite clear
      demonstration of its beneficial effect on reducing the incidence of serious head
      injury. Several interventions have been reported, with variable results and
      costs. Much of the recent literature has focused on child cyclists and on
      demographic factors associated with helmet use. This paper reports on helmet use
      by children and adults in a sample of 652 riders in an affluent southeast
      Michigan region, chosen to minimize the effect of previously recognized
      socioeconomic negative predictors that are not readily changed by intervention.
      Subjects were classified by age, sex, location, riding surface, type of bicycle,
      child bicycle seat use, child bicycle trailer use, and helmet use by companions.
      Overall helmet use was 24 percent; infants and toddlers had the highest rate of
      helmet use at 61 percent, followed by adults at 26 percent and school-aged
      children at 17 percent. The strongest predictor of helmet use in all age
      categories was the presence of a helmeted companion. Adult helmet use was also
      positively predicted by riding in the street and by riding a racing-type bicycle.
      The use of a city-type bicycle negatively predicted helmet use. For non-adults,
      female sex and the use of a child seat or trailer were positive predictors.
      Fostering peer pressure to increase helmet use may be an effective yet relatively
      inexpensive way to achieve the goal of widespread use of bicycle helmets.

PMID- 8153283
TI  - NICHD funds studies of contraceptive vaccines.

PMID- 8153284
TI  - HRSA awards cities $160 million in Ryan White AIDS grants.

PMID- 8153285
TI  - NLM offers free access to electronic AIDS data.

PMID- 8153286
TI  - Involvement of the kidneys in Mediterranean spotted fever and murine typhus.
AB  - We reviewed 58 patients, 27 with murine typhus (MT) and 31 with Israeli
      Mediterranean spotted fever (IMSF), hospitalized at the Sheba Medical Center 1979
      1988. Five patients with MT and five with IMSF had evidence of renal impairment.
      One patient with MT underwent a renal biopsy, and two patients with IMSF died and
      had autopsy examinations with histology of the kidney. The principal
      histopathological lesion found in those most severe cases of rickettsiosis
      induced renal failure was multifocal perivascular interstitial nephritis. In
      contrast with previous reports, involvement of the kidneys in rickettsial
      infection seems to be relatively common. Early diagnosis and treatment with
      hydration and specific antimicrobial agents is mandatory to prevent morbidity.

PMID- 8153287
TI  - Urinary sodium excretion in patients with nephrotic syndrome, and its circadian
      variation.
AB  - We analysed sodium excretion and its circadian variation in 70 patients with
      nephrotic syndrome and 19 healthy controls over 1-3 days, with a regimen of bed
      rest and constant sodium intake around the clock. We sampled urine and blood and
      took their blood pressure every 3 h. We also scored 60 renal biopsies for
      presence of interstitial fibrosis and tubular atrophy. Peripheral oedema was
      estimated in 37 patients. Fifty-nine patients excreted > 10 mmol sodium per 24 h,
      in equilibrium with dietary intake. In group A (n = 24), sodium excretion
      followed a normal circadian rhythm, with a daytime peak. In group B (n = 35), 29
      had reversed circadian rhythm with a night-time peak, and 6 had no apparent
      rhythm. Nephrotic syndrome was more severe in group B than in A (serum albumin
      19.5 vs. 24.1 g/l, p < 0.05; oedema 7.0 vs. 3.8 kg, p < 0.01). Group B also had
      signs of more advanced renal disease (GFR 49 vs. 99 ml/min; number of biopsies
      with tubulo-interstitial damage: 20/28 vs. 4/23; p < 0.001). Reversed sodium
      rhythm was associated with reversed circadian rhythms for GFR, effective renal
      plasma flow and urine flow, and blunting or reversal of the day-night differences
      in blood pressure and plasma renin activity. Eleven patients had urinary sodium
      excretion < 1 mmol/24 h. With respect to severity of nephrosis, they resembled
      group B, but GFR and incidence of tubulointerstitial lesions were like group A.
      Half of the patients with nephrotic syndrome had reversed circadian rhythm for
      sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153288
TI  - Delayed cerebral radiation necrosis.
AB  - The clinical features and long-term outcome of seven patients with delayed
      cerebral radiation necrosis (DCRN) are described. Radiotherapy had been given for
      pituitary tumour (1), astrocytoma (2), pinealoma (2), craniopharyngioma (1) and
      parotid carcinoma (1). The mean latency to onset of the first neurological
      symptoms was 22 months (range 6-40 months), and mean duration of follow-up was 86
      months (range 60-126). Three patients died at a mean of 84 months after
      radiotherapy (range 62-98). A fourth patient probably died from metastatic
      disease. Three patients remain alive, albeit severely disabled, after 5-10 years.
      The illness typically ran a stepwise course, with fits and stroke-like episodes
      occurring against a background of progressive dementia and somnolence. CT and MRI
      scans showed progressive ventricular dilatation associated with cerebral atrophy
      and diffuse or focal changes in the white matter. Four patients had had two or
      more neurosurgical procedures after the radiotherapy. In only one of the seven
      patients was the diagnosis made at presentation. DCRN produces a distinctive
      clinical picture, yet remains a poorly recognized complication of cranial
      irradiation.

PMID- 8153289
TI  - Hyperinsulinaemia in ischaemic heart disease: the importance of myocardial
      infarction and left ventricular function.
AB  - Elevated circulating insulin levels have been reported in ischaemic heart
      disease, and may be of aetiological importance. Previous studies have not
      considered the potential influence of heart failure or of previous myocardial
      infarction, as opposed to stable angina. We therefore measured the insulin
      response to a 75 g oral glucose tolerance test in five groups with normal glucose
      tolerance, comparing normal male controls to men with chronic stable angina, men
      with recent myocardial infarction (two groups, 3 weeks and 3 months post
      infarction), and men with chronic severe heart failure. Only patients with
      chronic heart failure had fasting hyperinsulinaemia, probably reflecting
      associated neuroendocrine abnormalities. Stimulated hyperinsulinaemia was present
      in all patient groups, but was less pronounced and of shorter duration in
      patients with angina. At 120 min, only patients with heart failure or previous
      myocardial infarction were hyperinsulinaemic. The degree of stimulated
      hyperinsulinaemia was not influenced by the presence of heart failure or by the
      length of time from infarction. Hyperinsulinaemia is associated with impaired
      peripheral muscle glucose uptake and metabolism, and might contribute to muscular
      fatigue on exertion in patients with previous myocardial infarction or heart
      failure.

PMID- 8153290
TI  - Issues in Huntington's disease testing.
AB  - The gene that is mutated in Huntington's disease has a polymorphic (CAG)n tract
      close to the 5' end of its message that is unstable and abnormally expanded in
      disease chromosomes. Rapid PCR tests that measure the CAG repeat number in this
      gene will become an important clinical tool. However, this test should be
      approached with caution, as its specificity and sensitivity have not been
      absolutely determined. The possibility that one might be able to predict the age
      of onset from the size of the CAG expansion in cases that have more than 50
      repeats has been considered. We have also made a case for retaining the
      diagnostic option of prenatal exclusion testing.

PMID- 8153291
TI  - Liposomal amphotericin B (AmBisome) in Mediterranean visceral leishmaniasis: a
      multi-centre trial.
AB  - Thirty-one patients with visceral leishmaniasis (VL) caused by Leishmania
      infantum received liposomal amphotericin B (AmBisome) in a multi-centre study.
      Ten immunocompetent patients (six children) received 1-1.38 mg/kg/day for 21
      days, and ten (nine children) received 3 mg/kg/day for 10 days. All were cured
      without significant adverse events and without relapse during 12-24 months of
      follow-up. Eleven immunocompromised adults, including seven co-infected with HIV
      (four with AIDS) received 100 mg (1.38-1.85 mg/kg) daily for 21 days. All were
      initially considered cured, but eight relapsed clinically and parasitologically
      at 3-22 months. Liposomal amphotericin B is a new, safe and effective drug for
      the treatment of VL.

PMID- 8153292
TI  - Localization of metastatic gastroenteropancreatic tumours by somatostatin
      receptor scintigraphy with [111In-DTPA-D-Phe1]-octreotide.
AB  - Most gastroenteropancreatic tumours express somatostatin receptors, allowing
      imaging using radiolabelled somatostatin analogues. Octreotide can be modified by
      coupling a DTPA moiety to the N-terminal D-phenylalanine to allow labelling with
      In111. We studied the comparative effectiveness of this radiopharmaceutical in
      identifying tumour extent. Twenty-two patients with metastatic
      gastroenteropancreatic tumours were scanned using [111In-DTPA-D-Phe1]-octreotide.
      In 11 patients with the carcinoid syndrome, one of six primary lesions was
      identified by CT scanning and by [111In-DTPA-D-Phe1]-octreotide scanning. Hepatic
      metastases were present in all patients, 9 of whom had positive scintigraphy. Two
      other sites of intra-abdominal uptake and four distant sites, not previously
      identified, were demonstrated. Five other distant sites were confirmed to be
      carcinoid metastases. All 11 patients with other gastroenteropancreatic tumours
      had positive scans, demonstrating 7/9 primary lesions, 12 intra-abdominal
      lesions, including hepatic metastases in all cases, and one distant lesion, all
      previously identified. Thus [111In-DTPA-D-Phe1]-octreotide imaging effectively
      identified the extent of metastatic disease from gastroenteropancreatic tumours,
      and confirmed lesions whose significance was uncertain following previous imaging
      procedures.

PMID- 8153293
TI  - An audit of cardiac surgery in patients aged over 70 years.
AB  - With an increasingly aged population, the number of patients requiring treatment
      for cardiovascular diseases will rise. Previous expectations of cardiac surgery
      in the over-seventies have been poor, with surgery being very much a last resort.
      We decided to test whether this was appropriate, and to determine whether the
      priority of surgery affected the outcome. Three hundred and six patients over the
      age of 70 were operated on in our unit in a 4 1/2-year period, 210 as elective
      operations and 96 as emergencies. Eighty-nine per cent were in NYHA class III-IV
      pre-operatively and half had other significant medical problems. Most (46%)
      underwent coronary artery surgery. The methods used were identical to those used
      for the younger patients in both operative approach and post-operative
      management. The overall mortality was 6.9%; 1.9% for elective procedures and
      16.7% for emergencies (12.3% when catastrophic pathologies are excluded).
      However, the morbidity was not significantly different between the two groups and
      the length of post-operative ventilation and hospital stay were likewise not
      significantly different. Follow-up of the survivors showed no late deaths, and
      87% were in NYHA class I and II. Of the others, 25 have required additional
      hospital admissions for associated cardiac problems. One required another
      invasive procedure (a PTCA), but none has required further surgery. The findings
      of low mortality for elective cardiac surgery in this age group are in agreement
      with other reports. If early referral prevents emergency surgery, it should be
      avidly pursued, in view of the improved outcome for elective surgery.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8153294
TI  - Postinfectious glomerulonephritis--is there a link to alcoholism?
AB  - From January 1984 to May 1993, we observed 30 cases of postinfectious
      glomerulonephritis (GN)--endocapillary, exudative GN with humps (23 males, 7
      females; median age 49 years; range 17-77). They represented 4.5% of all renal
      biopsies. Crescents were present in 9/26 who had renal biopsies (35%) and there
      was a mesangioproliferative pattern in 14 (54%). Seventeen of the 30 patients
      (57%) were alcoholics by history and biochemistry. Cirrhosis was present in 8/17
      (47%), but alcoholic hepatitis in none. Nine of the 17 alcoholic (53%) but none
      of the non-alcoholic patients developed chronic renal failure. Adverse renal
      prognosis was significantly correlated to alcoholism. We conclude that (i)
      alcoholism is common in patients with postinfectious GN, and, (ii) alcoholism
      adversely affects renal prognosis in patients with postinfectious GN.

PMID- 8153295
TI  - Imaging of epiphyseal injuries.
AB  - There have been many advances in the diagnosis and treatment of epiphyseal
      injuries in the 30 years since the publication of the landmark article by Drs
      Robert Salter and William Harris. They are the subject of this review. The
      anatomic features of the physis, epiphysis, and metaphysis are presented, and
      histologic studies of human and experimental physeal injuries are described. The
      recently recognized histologic, anatomic, and imaging characteristics of bone
      bridging of the physis resulting in growth disturbances are reviewed.
      Modification in and additions to the original Salter-Harris classification system
      have been proposed. The role and technique of computed tomography and magnetic
      resonance imaging in the assessment of the initial injury and analysis of
      subsequent growth disturbance are discussed.

PMID- 8153296
TI  - Should metallic vascular stents be used to treat cerebrovascular occlusive
      diseases?
AB  - The risks of metallic stent deployment are quite low, and the likelihood of
      restenosis due to intimal hyperplasia is relatively high, particularly in small
      to medium-size vessels. The goal of all cerebrovascular interventions is to
      alleviate symptoms and prevent stroke. For symptomatic carotid bifurcation
      stenosis, insufficient information is available regarding carotid PTA and stent
      placement to make any recommendations. Carotid endarterectomy is the treatment of
      choice in patients with a 70%-99% stenosis of the involved internal carotid
      artery. For internal carotid artery dissection, stent placement seems to be a
      reasonable therapeutic alternative that may eventually assume a position as an
      accepted therapeutic alternative alongside surgery and anticoagulation. The
      gathering of level I and level II evidence by means of well-designed clinical
      trials is encouraged. Similarly, the application of stent placement to occlusive
      disorders of the dural venous sinuses is intriguing. Additional clinical studies
      should help define the role of stents in these diseases.

PMID- 8153297
TI  - Neurovascular stents.

PMID- 8153298
TI  - Can computers help radiologists read mammograms?

PMID- 8153299
TI  - Mammography (and radiology?) is still plagued with poor quality in photographic
      processing and darkroom fog.

PMID- 8153300
TI  - When in doubt, sound it out.

PMID- 8153301
TI  - National survey of mammographic facilities in 1985, 1988, and 1992.
AB  - PURPOSE: To determine trends in mammography in the United States. MATERIALS AND
      METHODS: A sample of mammographic facilities was selected for each year of the
      Nationwide Evaluation of X-ray Trends. The same protocol was followed for the
      1985, 1988, and 1992 surveys. Data were collected with use of the same imaging
      phantom for all three surveys and also with a different phantom in the 1988 and
      1992 surveys. RESULTS: Of the 356 facilities surveyed in 1992, 59% claimed to be
      in compliance with the Health Care Financing Administration (HCFA) mammography
      requirements, 42% were accredited by the American College of Radiology (ACR), and
      23% did not hold credentials from either the HCFA or the ACR. Since 1985, there
      has been a 34% improvement in acceptable phantom image quality score and a 20%
      decrease in the mean glandular dose. CONCLUSION: Mammography as practiced today
      is essentially a screen-film technique. Mammographic phantom image quality has
      improved considerably. The overall mean glandular dose has decreased primarily
      because of the elimination of xeroradiography.

PMID- 8153302
TI  - Computer-aided mammographic screening for spiculated lesions.
AB  - PURPOSE: To study the use of a computer vision method as a second reader for the
      detection of spiculated lesions on screening mammograms. MATERIALS AND METHODS:
      An algorithmic computer process for the detection of spiculated lesions on
      digitized screen-film mammograms was applied to 85 four-view clinical cases: 36
      cases with cancer proved by means of biopsy and 49 cases with negative findings
      at examination and follow-up. The computer detections were printed as film with
      added outlines that indicated the suspected cancers. Four radiologists screened
      the 85 cases twice, once without and once with the computer reports as ancillary
      films. RESULTS: The algorithm alone achieved 100% sensitivity, with a specificity
      of 82%. The computer reports increased the average radiologist sensitivity by
      9.7% (P = .005), moving from 80.6% to 90.3%, with no decrease in average
      specificity. CONCLUSION: The study demonstrated that computer analysis of
      mammograms can provide a substantial and statistically significant increase in
      radiologist screening efficacy.

PMID- 8153303
TI  - Masses in breasts with implants: diagnosis with US-guided fine-needle aspiration
      biopsy.
AB  - PURPOSE: To evaluate retrospectively the findings at ultrasound (US)-guided fine
      needle aspiration biopsy (FNAB) of masses in breasts that contain a prosthesis.
      MATERIALS AND METHODS: Real-time US-guided FNAB was performed in 22 lesions in 17
      patients with breast implants. Pneumocystography was performed in seven of eight
      cysts. The final diagnosis was based on either histologic findings after surgical
      excision or a combination of cytologic, imaging, and clinical findings. RESULTS:
      The lesions had a mean diameter of 15 mm +/- 9 (standard deviation). Fifteen
      lesions (68%) were not identified on mammograms. In all cases, FNAB was completed
      without complication. Pneumocystography was successful in seven of seven cysts.
      Cytologic diagnosis was correct in 21 of 22 lesions (95%). There was one case of
      inadequate specimen (5%). In 16 cases (73%), the diagnosis was established with a
      single pass. CONCLUSION: Real-time US allowed continuous visualization of the
      needle during insertion and sampling, which resulted in pinpoint accuracy and
      safety. US-guided FNAB is recommended for needle biopsy in breasts with implants.

PMID- 8153304
TI  - Spectrum of pulmonary nontuberculous mycobacterial infection.
AB  - PURPOSE: To organize pulmonary nontuberculous mycobacterial (NTMB) infections
      into a classification system based on clinical and radiographic features.
      MATERIALS AND METHODS: Scientific literature was reviewed and organized into a
      framework of clinical-radiographic syndromes of NTMB infection. RESULTS: NTMB
      infection was classified into five clinical-radiographic syndromes. The
      "classical" form radiographically mimics tuberculosis. It is seen predominantly
      in white male patients with underlying chronic obstructive lung disease.
      "Nonclassical" disease radiographically appears as nodular infiltrates and
      bronchiectasis in a sporadic distribution. It characteristically occurs in
      elderly women without underlying chronic illness. Asymptomatic nodules are
      another manifestation. Immunocompromised individuals develop disseminated
      infection, often with few or no pulmonary symptoms but various chest radiographic
      manifestations. Patients with achalasia have a radiographic appearance that most
      often resembles aspiration pneumonia. CONCLUSION: Most pulmonary NTMB infections
      can be classified into one of five categories, which helps in the understanding
      of these wide-ranging manifestations.

PMID- 8153305
TI  - Pulmonary arteries and lung parenchyma in chronic pulmonary embolism:
      preoperative and postoperative CT findings.
AB  - PURPOSE: To evaluate the role of computed tomography (CT) in diagnosis of chronic
      thromboembolic pulmonary hypertension, assessment of surgical operability, and
      follow-up after surgery. MATERIALS AND METHODS: Seventy-five patients with
      chronic thromboembolism were examined with CT; 63 underwent
      thromboendarterectomy, and postoperative CT scans were acquired in 23. CT scans
      were analyzed for vascular and parenchymal changes, and findings were compared
      with those on lung scintigrams and with surgical results. RESULTS: CT findings
      allowed confirmation of the diagnosis of chronic thromboembolism and ensured
      technical operability (sensitivity, 77%; specificity, 100%; overall accuracy,
      80%) by means of direct visualization of thrombi in central pulmonary arteries in
      53 patients. CONCLUSION: CT enables demonstration of pulmonary thromboembolism
      with criteria pertaining to pulmonary arteries and to lung parenchyma and enables
      assessment of technical operatibility and confirmation of surgical success.

PMID- 8153306
TI  - Chronic pulmonary thromboembolism: detection of regional hypoperfusion with CT.
AB  - PURPOSE: To study the relationship of regional hypoperfusion and areas of
      decreased lung attenuation on computed tomographic (CT) scans of patients with
      chronic pulmonary thromboembolism. MATERIALS AND METHODS: Preoperative CT scans
      of five patients (four men and one woman, aged 29-72 years) with chronic
      pulmonary thromboembolism were reviewed and compared with axial single photon
      emission CT (SPECT) perfusion scans obtained at similar levels. Regions of
      varying attenuation and perfusion were scored on a three-point scale. RESULTS: In
      the five patients, 198 regions were identified. Of 176 abnormal regions at SPECT,
      133 were abnormal at CT (sensitivity, 75.6%). Eleven of 22 regions interpreted as
      normal at SPECT were judged to have normal attenuation at CT (specificity, 50%).
      The overall accuracy of CT for detecting areas of hypoperfusion was 72.7% (P =
      .011). CONCLUSION: A mosaic pattern of lung attenuation at CT is a sign of
      variable regional perfusion and may suggest chronic pulmonary thromboembolism as
      a cause for pulmonary hypertension.

PMID- 8153307
TI  - Pleural invasion by peripheral bronchogenic carcinoma: assessment with three
      dimensional helical CT.
AB  - PURPOSE: To evaluate the potential role of three-dimensional (3D) computed
      tomography (CT) in assessment of pleural invasion by peripheral bronchogenic
      carcinoma. MATERIALS AND METHODS: Twenty-four-second helical CT scans were
      obtained during a single breath hold in 42 consecutive patients with peripheral
      bronchogenic carcinoma. Conventional two-dimensional (2D) images and 3D
      reconstruction images were reviewed independently by three blinded observers, who
      reached a decision by consensus. All patients underwent surgical resection of the
      tumor, and CT findings were correlated with the findings in pathologic specimens.
      RESULTS: Twelve patients had visceral pleural invasion, five had parietal pleural
      invasion, and 25 had no evidence of pleural invasion. Visceral pleural invasion
      was identified on 2D CT images in two patients and on 3D reconstructions in 11.
      Parietal pleural invasion was identified on 2D CT images in two patients and on
      3D reconstructions in three. CONCLUSION: 3D reconstruction imaging is superior to
      conventional 2D CT in assessment of pleural invasion by peripheral bronchogenic
      carcinoma.

PMID- 8153308
TI  - Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion
      images: preliminary prospective evaluation.
AB  - PURPOSE: To evaluate use of positron emission tomography (PET) with 2-[fluorine
      18]-fluoro-2-deoxy-D-glucose (FDG) in detection of mediastinal lymph node
      metastases from non-small cell lung cancer. MATERIALS AND METHODS: A prospective
      trial to compare FDG PET and computed tomography (CT) of the thorax was performed
      in 23 patients with newly diagnosed or suspected non-small cell lung cancer.
      Blinded interpretations of CT alone, PET alone, CT and PET together, and fusion
      images were performed, and the results were compared with pathologic results.
      RESULTS: Nineteen of 23 patients had non-small cell lung cancer. Prevalence of
      mediastinal involvement was 41%. In staging disease in the mediastinum, CT alone
      was 64% sensitive, 44% specific, and 52% accurate, whereas PET alone and fusion
      images were 82% sensitive, 81% specific, and 81% accurate (P < .05). CONCLUSIONS:
      FDG PET was more accurate than CT in staging disease in the mediastinum in
      patients with lung cancer and appears to be the preferred imaging method in this
      clinical setting.

PMID- 8153309
TI  - Persistent or recurrent bronchogenic carcinoma: detection with PET and 2-[F-18]-2
      deoxy-D-glucose.
AB  - PURPOSE: To assess positron emission tomography (PET) with 2-[fluorine-18]-2
      deoxy-D-glucose (FDG) in the differentiation of recurrent bronchogenic carcinoma
      from fibrosis after therapy. MATERIALS AND METHODS: Any patient treated for
      bronchogenic carcinoma who had a residual chest radiographic abnormality was
      eligible. Forty-three patients (mean age, 63.5 years) participated. Chest
      radiographs and thoracic computed tomographic scans helped localize the
      abnormality prior to PET. Semiquantitative analysis was performed on FDG PET
      images with calculated standardized uptake ratios (SURs). Sensitivity,
      specificity, and confidence intervals for recurrent disease were determined.
      RESULTS: Thirty-five patients had recurrent or persistent tumor (median SUR, 7.6;
      range, 1.9-18.7). Eight patients had fibrosis but no evidence of disease (SUR,
      1.6; range, 0.6-2.4). The sensitivity for detecting recurrent tumor (SUR > 2.5)
      was 97.1%, and specificity was 100%. The SUR for recurrent tumor was
      statistically significantly higher than for fibrosis (P = .0001). CONCLUSION: FDG
      PET accurately helps differentiate recurrent bronchogenic carcinoma from
      fibrosis.

PMID- 8153310
TI  - Chronic diffuse infiltrative lung disease: determination of the diagnostic value
      of clinical data, chest radiography, and CT and Bayesian analysis.
AB  - PURPOSE: To assess the value of clinical, chest radiographic, and computed
      tomographic (CT) findings in classifying chronic diffuse infiltrative lung
      disease (CDILD) MATERIALS AND METHODS: Two samples from the same population were
      consecutively studied: the training set (group A, n = 208) for the development of
      the decision aid and the test set (group B, n = 100) for validation. Computer
      aided diagnoses were made with a Bayesian model that assigned to each patient
      diagnostic probabilities based on clinical, radiographic, or CT variables.
      RESULTS: In group A, a correct diagnosis based on clinical data was obtained in
      29% of cases; radiography, 9%; and CT, 36%. This increased to 54% when clinical
      and radiographic variables were combined (P < .0001) and to 80% when data from
      all three were analyzed together (P < .0001). With prior and conditional
      probabilities determined from group A, the frequency of correct diagnosis in
      group B was 27% with clinical data, which increased to 53% (P < .0001) with
      radiographic findings and 61% after including CT data (P = .07). CONCLUSION: CT
      can help determine the specific diagnosis in patients with CDILD.

PMID- 8153311
TI  - Mediastinal masses: alternative approaches to CT-guided needle biopsy.
AB  - PURPOSE: To determine how the use of alternative anatomic approaches to
      mediastinal masses in biopsies guided with computed tomography (CT) affects
      success and complication rates. MATERIALS AND METHODS: The medical records and
      imaging studies in 36 consecutive patients who underwent percutaneous mediastinal
      biopsy were reviewed. Alternative techniques to avoid penetration of the visceral
      pleura during biopsy of mediastinal masses were used in 12 patients. These
      included a pleural space approach through pleural effusion or iatrogenic
      pneumothorax, lateral decubitus positioning, and direct semicoronal scanning to
      guide suprasternal biopsy. RESULTS: Adequate material for diagnosis was obtained
      in 34 of 36 patients (94%), 22 of 22 biopsies (100%) of anterior mediastinal
      masses, six of eight biopsies (75%) of middle mediastinal masses, and six of six
      biopsies (100%) of posterior mediastinal masses. Pneumothorax occurred in two of
      36 patients (6%); this low complication rate was associated with infrequent use
      of the transpulmonary approach. CONCLUSION: CT guidance can enable an
      individualized approach to a mediastinal mass to avoid penetration of the
      visceral pleura, large blood vessels, and bronchial tree and thereby lower the
      rate of complications.

PMID- 8153312
TI  - Three-dimensional US: preliminary clinical experience.
AB  - PURPOSE: To evaluate applications of three-dimensional (3D) ultrasound (US) in a
      clinical setting. MATERIALS AND METHODS: Sixty-two patients were examined with
      experimental 3D US transducers coupled to a commercially available US unit and a
      computer workstation. Images were acquired in either the sagittal or transverse
      plane and were reconstructed in two orthogonal planes, transverse and sagittal;
      the C-plane, parallel to the transducer surface; and a volumetric rotational
      transparency display. RESULTS: A variety of normal and diseased abdominal and
      superficial organs and selected fetal anatomy, and pathologic conditions were
      imaged. 3D US allowed display of anatomy and pathologic conditions in planes
      usually not possible with conventional two-dimensional (2D) US. CONCLUSION:
      Preliminary data suggest that 3D US may become a valuable clinical tool and
      adjunct to 2D US. 3D US allows depiction of normal and abnormal structures in
      previously unattainable planes, thus facilitating diagnosis and increasing
      operator diagnostic confidence.

PMID- 8153313
TI  - Transient epiphyseal lesions in renal transplant recipients: presumed
      insufficiency stress fractures.
AB  - PURPOSE: To determine epiphyseal abnormalities in renal transplant recipients.
      MATERIALS AND METHODS: Initial and final findings on serial conventional
      radiographs and magnetic resonance (MR) images obtained in symptomatic joints of
      transplant recipients were determined and correlated. RESULTS: In 42 of 47
      joints, T1-weighted MR images depicted 106 ill-delimited areas of low signal
      intensity. At 1-year follow-up, all lesions had disappeared. T1-weighted MR
      images depicted nine well-delimited regions of normal signal intensity delineated
      by a rim of low signal intensity in seven joints. No lesion had completely
      disappeared at follow-up. Initial radiographs either were normal or showed patchy
      osteoporosis (13 joints). Follow-up radiographs showed epiphyseal collapse of two
      femoral heads, with well-delimited lesions on MR images, and subtle subchondral
      sclerosis in 21 noncollapsed epiphyses. CONCLUSION: Initial MR imaging patterns
      of transient lesions (92% of lesions) are different from those of irreversible
      lesions. Transient lesions suggest insufficiency stress fractures, while
      irreversible lesions suggest avascular osteonecrosis.

PMID- 8153314
TI  - Epiphyseal scar of the femoral head: risk factor of osteonecrosis.
AB  - PURPOSE: To find out whether a correlation exists between the presence of
      epiphyseal scar within the femoral head and osteonecrosis at examination with
      magnetic resonance (MR) imaging. MATERIALS AND METHODS: A total of 117 femoral
      heads in 60 patients were examined. Lipogenic factors (defined as either the use
      of steroid or alcohol abuse) were positive in 46 patients (average age, 37 years)
      and absent in 14 (average age, 47 years). Both hip joints were examined
      simultaneously at 1.5 T; three pulse sequences were used in each imaging study.
      All images were interpreted for type of epiphyseal scar and presence or absence
      of osteonecrosis. RESULTS: Six types of epiphyseal scar (A-F), each with a
      different shape, were seen. A total of 72 femoral heads had type A or B sealed
      off scars; 32 of these 72 had osteonecrosis. Of the 45 femoral heads with type C,
      D, E, or F perforated scars, only one had osteonecrosis. The difference between
      these two groups was statistically significant (P < .001). CONCLUSION: The
      presence of a sealed-off epiphyseal scar was associated with a very high risk of
      osteonecrosis of the femoral head.

PMID- 8153315
TI  - MR imaging of the arthritic knee: improved discrimination of cartilage, synovium,
      and effusion with pulsed saturation transfer and fat-suppressed T1-weighted
      sequences.
AB  - PURPOSE: To assess the applicability of three-dimensional (3D) magnetic resonance
      (MR) imaging with pulsed saturation transfer (ST) or fat saturation in depicting
      articular structures in arthritic knees. MATERIALS AND METHODS: Eleven patients
      underwent MR imaging with T1-weighted spin-echo (SE); unenhanced and contrast
      material-enhanced T2*-weighted 3D gradient-echo with and without on-resonance
      pulsed ST; and T1-weighted, fat-presaturated 3D gradient-echo techniques. Images
      with ST were subtracted from those without ST. RESULTS: Both fat-suppressed
      imaging and ST-subtraction (STS) techniques generated a high contrast-to-noise
      ratio among cartilage, synovium, effusion, bone, and adipose tissue. Both
      techniques depicted hypertrophic synovial tissue on unenhanced images; contrast
      material was necessary to differentiate between synovium and cartilage on STS
      images. CONCLUSION: 3D MR imaging with fat-suppressed or STS techniques provides
      good discrimination among articular structures in arthritic knees. Fat-suppressed
      imaging is faster than STS imaging and offers better contrast between cartilage
      and synovium. These techniques may improve monitoring of arthritic disease
      progression and therapeutic response.

PMID- 8153316
TI  - Changes in tumor perfusion induced by chemotherapy in bone sarcomas: color
      Doppler flow imaging compared with contrast-enhanced MR imaging and three-phase
      bone scintigraphy.
AB  - PURPOSE: To prospectively evaluate color Doppler flow imaging (CDFI) with
      spectral analysis versus dynamic gadolinium-enhanced magnetic resonance (MR)
      imaging and three-phase bone scintigraphy in monitoring the effect of
      chemotherapy on bone sarcomas. MATERIALS AND METHODS: Seventeen osteosarcomas and
      five Ewing sarcomas were examined with these imaging techniques before and after
      chemotherapy. Results were compared with the histopathologic response. RESULTS:
      Before chemotherapy, high systolic Doppler frequency shifts (DFSs) and/or low
      impedance Doppler signals were found in all but one tumor. Resistive indexes
      (RIs) in tumor-feeding arteries were substantially lower than in contralateral
      normal arteries. After chemotherapy, DFSs disappeared in five of seven good
      respondents and remained substantial in all but one poor respondent. RIs
      increased substantially in all good respondents and decreased or showed minor
      changes only in all but one poor respondent. CONCLUSION: CDFI with spectral
      analysis has an advantage over the other two techniques in monitoring the
      efficacy of chemotherapy in bone sarcomas because of its superior accuracy,
      noninvasive nature, availability, and low cost.

PMID- 8153317
TI  - MR imaging and CT of surgical materials currently used in ophthalmology: in vitro
      and in vivo studies.
AB  - PURPOSE: To assess methods of imaging postoperative changes in the eyeball by
      performing in vitro and in vivo studies of the main solid and fluid materials
      used in the treatment of cataract and retinal detachment. MATERIALS AND METHODS:
      The samples were analyzed in vitro with computed tomography (CT) and magnetic
      resonance (MR) imaging performed at 0.5 T. In vivo studies were performed in
      seven patients who underwent lens implantation (n = 1), scleral buckling with
      hydrogel or silicone (n = 6), and retinopexy with gas or silicone oil (n = 6).
      The attenuation and signal intensity of the materials were compared with values
      for anatomic structures. RESULTS: Lens implants were difficult to visualize. Each
      scleral buckling and retinopexy material was easily differentiated from the
      others and from anatomic structures at both CT and MR imaging. CONCLUSION:
      Postoperative CT or MR imaging may be useful after retinal detachment surgery,
      particularly when ultrasound is not reliable after intravitreous gas-fluid
      interchange.

PMID- 8153318
TI  - Stent placement for arterial and venous cerebrovascular disease: preliminary
      experience.
AB  - PURPOSE: To report initial clinical experience with stent placement in the
      cerebrovascular circulation. MATERIALS AND METHODS: Four patients underwent
      arterial or venous stent placement. Two patients had cervical internal carotid
      artery dissections, with aneurysms and stenoses of the distal cervical carotid
      artery. Two patients had venous occlusive disease involving the major dural
      sinuses, with substantial pressure gradients across the stenoses. RESULTS:
      Immediately after stent placement, the true arterial lumina returned to normal
      diameter and both carotid aneurysms were more than 90% occluded. Follow-up
      angiography demonstrated continued improvement in the arterial aneurysms. Both
      patients with dural sinus venous occlusive disease showed substantial improvement
      of the sinus stenoses and substantial reversal of the pressure gradients after
      venous stent placement. At follow-up, these patients have done well. CONCLUSION:
      This preliminary experience suggests there may be a role for stents in the
      management of arterial and venous cerebrovascular disease, including carotid
      artery dissection and venous occlusive disease.

PMID- 8153319
TI  - Accurate frameless registration of MR and CT images of the head: applications in
      planning surgery and radiation therapy.
AB  - PURPOSE: To evaluate the feasibility and efficacy of a three-dimensional image
      registration technique for planning skull base surgery, performing frameless
      image registration for stereotaxic neurosurgery, and staging nasopharyngeal
      carcinoma. MATERIALS AND METHODS: Computed tomographic (CT) and magnetic
      resonance (MR) images from 35 patients were registered by identifying 12-16
      homologous landmarks with each modality. Images were displayed as overlaid
      sections or rendered three-dimensional scenes. The clarity of the combined images
      from 15 patients undergoing skull base surgery was compared with that of the
      conventional displays. RESULTS: Images were combined for three applications, with
      an accuracy of 1-2 mm. For the 15 patients undergoing skull base surgery, the
      combined images were significantly better at depicting the relationship between
      bone and lesion than conventional display (P < .01). CONCLUSION: MR and CT images
      of the head can be accurately registered without using external markers or
      substantially altering image acquisition protocols. The resulting images can show
      the radiologic information more clearly than conventional viewing.

PMID- 8153320
TI  - Current status of and a critique on methods used in the diagnosis of imaged
      breast abnormalities: a surgeon's view.

PMID- 8153321
TI  - Location of the corticospinal tract in the internal capsule at MR imaging.
AB  - PURPOSE: To examine whether hyperintense foci in the posterior internal capsule
      (IC) on T2-weighted magnetic resonance (MR) images represent fibers of the
      corticospinal tract (CST). MATERIALS AND METHODS: The authors reviewed MR images
      of 100 control subjects and 35 patients with amyotrophic lateral sclerosis (ALS)
      and brain specimens from seven control subjects and five ALS patients. RESULTS:
      In the posterior IC, the brain specimens from control subjects demonstrated a
      pale area with large axons and thick myelin sheaths. In five ALS patients, the
      brain specimens showed degeneration of the CST in the same region. MR images
      demonstrated abnormal hyperintensity that represented degeneration of the CST in
      five of 35 ALS patients. In the same region, hyperintense foci were found in the
      control subjects. CONCLUSION: Normal hyperintense foci in the IC represent the
      fibers of the CST. The presence of large fibers with thick myelin sheaths may
      play an important role in these signal intensity variations.

PMID- 8153322
TI  - Technology for FDG SPECT with a relatively inexpensive gamma camera. Work in
      progress.
AB  - PURPOSE: At the time of the co-development of a commercial dual-headed gamma
      camera for whole-body single photon emission computed tomography (SPECT),
      modifications were made to permit imaging of 511-keV photons (from positron
      emitters) while maintaining versatility and cost-effectiveness in nuclear
      medicine for routine nonpositron studies. MATERIALS AND METHODS: Special
      collimators were made, and gantry stability was increased. Detector shielding and
      crystal thickness were not changed. In phantoms, healthy volunteers (two men,
      aged 34 and 38 years), and 109 patients (71 male and 38 female patients, aged 2
      74 years [mean, 56 years]), SPECT was performed with 2-[fluorine-18]fluoro-2
      deoxy-D-glucose (FDG). In patients, 36 myocardial viability, 47 oncologic, and 26
      brain examinations were performed. RESULTS: All FDG SPECT scans were subjectively
      judged to be of acceptable quality. Preliminary results in regard to diagnostic
      findings are reviewed; this analysis is intended to be a feasibility study not a
      conclusive review of imaging accuracy. CONCLUSION: FDG SPECT provides images that
      are interpretable for cardiac or oncologic diagnosis, without the need for or
      expense of a positron emission tomography (PET) center or a dedicated PET
      scanner.

PMID- 8153323
TI  - Aortic dissection caused by angiographic procedures.
AB  - PURPOSE: To describe findings in, and the clinical course and outcome of, aortic
      dissection (dissecting aneurysm) caused by angiographic procedures. MATERIALS AND
      METHODS: The records of approximately 15,500 angiographic procedures performed
      between 1985 and 1991 were reviewed. In the six cases of iatrogenic aortic
      dissection identified, computed tomography (CT) was performed for diagnosis,
      follow-up, or both. RESULTS: The type of aortic dissection was Stanford type A in
      three patients and Stanford type B in three patients. The sites of injury were
      the abdominal aorta (n = 2), right brachiocephalic artery (n = 2), middle of the
      thoracic aorta (n = 1), and right common iliac artery (n = 1). One patient had
      anterograde dissection from the site of injury; two patients, retrograde
      dissection; and three patients, extensive dissection that extended in both
      anterograde and retrograde directions. Retrograde dissections decreased in size
      or disappeared in 1-3 months due to the absence of reentry, whereas anterograde
      dissections persisted during follow-up (15-27 months). All patient were treated
      without surgery. CONCLUSION: Angiographers should be aware of this potentially
      serious complication. The extent and type of the aortic dissection can be
      determined with CT.

PMID- 8153324
TI  - Life-threatening pulmonary emboli and cor pulmonale: treatment with percutaneous
      pulmonary artery stent placement.
AB  - Large, central bilateral pulmonary emboli led to cor pulmonale and severe
      hypoxemia in a patient who had recently undergone cardiac surgery. After
      percutaneous catheter fragmentation and thrombolysis of the emboli failed, the
      left and right interlobal pulmonary arteries were recanalized by placement of
      self-expanding Wallstent endoprostheses through the clots. Pulmonary perfusion
      was restored to the lower lobes, and the patient demonstrated rapid clinical
      improvement.

PMID- 8153325
TI  - Clinical results of transvenous systemic embolotherapy with a neuroradiologic
      detachable balloon.
AB  - PURPOSE: To evaluate the efficacy of transvenous systemic embolotherapy with a
      neuroradiologic detachable balloon. MATERIALS AND METHODS: As part of a clinical
      trial, a detachable silicone balloon was used to occlude pulmonary arteriovenous
      malformations (PAVMs) in 35 patients and varicocele in 14 patients. In patients
      with PAVM, the indications for embolotherapy were prophylaxis against paradoxic
      embolization (n = 35) and dyspnea, fatigue, or both (n = 26); in patients with
      varicocele, they were pain or a discomforting lesion (n = 8) or infertility (n =
      6). RESULTS: Balloon embolotherapy was successful in 79 (98%) of the 81 lesions
      in which it was attempted; 29 (37%) of these 79 balloons were used in conjunction
      with coils. Ninety-six (97%) of 99 balloons were successfully placed; the three
      technical failures had no substantial clinical sequelae, and in all three,
      occlusion was eventually achieved with either detachable balloons or coils. Of
      six late deflations, five occurred in balloons placed adjacent to coils; only
      one, which occurred between 1 day and 21 days after placement, resulted in
      recanalization. CONCLUSION: Transvenous embolization with this detachable balloon
      was relatively simple and provided cross-sectional occlusion of PAVMs and
      varicocele.

PMID- 8153326
TI  - Vascular occlusion with a balloon-expandable stent occluder.
AB  - PURPOSE: To evaluate the effectiveness of a new vascular occlusion device.
      MATERIALS AND METHODS: The device was created by coating a balloon-expandable
      stent with a silicone sleeve that tapers to a blind-ended nozzle at its leading
      end. Once crimp-mounted on an angioplasty balloon catheter, the device is
      introduced over a guide wire through a small end hole in the nozzle. RESULTS: The
      device was tested for stability and occlusive ability. No migration was measured
      over a pulsatile pulse range of 50-300 mm Hg, and mean flow rate in the occluded
      vessel was reduced from 443 mL/min +/- 99 (standard deviation) to 1.9 mL/min +/-
      2.7. Subsequently, 12 arteries were occluded in three dogs, and immediate
      vascular occlusion was achieved in all vessels. An arteriovenous fistula was
      created in another six dogs and was successfully occluded with the device. Follow
      up arteriography at 3 months demonstrated persistent occlusion with no migration
      of the device. CONCLUSION: This new occlusive device offers immediate vascular
      occlusion with excellent stability.

PMID- 8153327
TI  - Iliofemoral deep venous thrombosis: aggressive therapy with catheter-directed
      thrombolysis.
AB  - PURPOSE: To evaluate the efficacy of catheter-directed thrombolysis with
      urokinase in treating symptomatic iliofemoral deep venous thrombosis (DVT).
      MATERIALS AND METHODS: Twenty-one consecutive patients with iliofemoral DVT
      underwent treatment for 27 affected limbs (acute DVT, n = 20; chronic DVT, n =
      7). The average urokinase dose was 4.9 million IU (range, 1.4 million to 16.0
      million IU) infused over an average of 30 hours (range, 15-74 hours). RESULTS:
      Lysis was complete in 18 (72%), partial in five (20%), and not achieved in two
      (8%) of 25 treated limbs. Two chronically occluded iliac veins could not be
      crossed with a guide wire and did not receive urokinase. Sixteen limbs had
      underlying venous stenoses (> 50%) that were treated with angioplasty (n = 2) or
      angioplasty and stent placement (n = 14). There were no major complications or
      clinically detectable pulmonary emboli. The technical and clinical success rates
      were 85%. CONCLUSION: This initial experience suggests that catheter-directed
      thrombolysis with urokinase for treatment of symptomatic iliofemoral DVT is safe
      and effective.

PMID- 8153328
TI  - Bloodstream infections after interventional procedures in the biliary tract.
AB  - PURPOSE: To assess the adequacy of prophylaxis for interventional radiologic
      biliary procedures and the etiologic organisms of subsequent bloodstream
      infections. MATERIALS AND METHODS: Data from 148 patients who underwent 480
      interventional radiologic biliary procedures were evaluated for evidence of
      bloodstream infection. Data analyzed included type of procedure performed,
      whether an antibiotic was used, and evidence of infectious complications
      occurring during and within 72 hours after the procedure. All culture data
      obtained before and after the procedure were recorded. RESULTS: Seven cases of
      new bloodstream infection were identified, five of which were caused by
      Enterococcus species. No substantial risk factors for bloodstream infection were
      identified, although it occurred only in patients who had recently undergone
      biliary surgery or underwent manipulations other than simple cholangiography.
      Microbial colonization of the bile was associated with older age. Evidence of
      possible or proved infection after the first interventional procedure was more
      common in patients with positive bile cultures. CONCLUSION: Although the
      importance of enterococcal bacteremia is uncertain, current recommendations for
      cephalosporin prophylaxis for interventional radiologic biliary procedures should
      be reevaluated.

PMID- 8153329
TI  - Percutaneous CT lymphography with perflubron: imaging efficacy in rabbits and
      monkeys.
AB  - PURPOSE: To evaluate the imaging efficacy of percutaneous lymphography performed
      with injection of perflubron emulsions and computed tomography (CT). MATERIALS
      AND METHODS: Thin-section CT was used to image lymph nodes in 116 rabbits and six
      monkeys. Quantitative measures of regional lymph node enhancement were obtained 4
      hours to 21 days after subcutaneous injection of perflubron (0.1-0.5 mL per
      injection site). Lymph node enhancement was calculated in Hounsfield units and
      converted to bromine concentration with standards that were imaged at the same
      time. RESULTS: Excellent enhancement of regional lymph nodes in both groups of
      animals was obtained. Nodal enhancement was linearly related to dose and was
      sustained for 20 days; maximum enhancement was seen 2 days after injection.
      Massage of the injection site increased delivery of the perflubron emulsion to
      regional lymph nodes. CONCLUSION: In rabbits and monkeys, percutaneous CT
      lymphography effectively depicts the intranodal distribution of macrophages in
      normal lymph nodes.

PMID- 8153330
TI  - Transcervical recanalization of strictures in the postoperative fallopian tube.
AB  - PURPOSE: To evaluate use of transcervical recanalization in patients with
      reocclusion of the proximal fallopian tube after failed surgery to reverse
      sterilization or failed tuboplasty to treat inflammatory disease. MATERIALS AND
      METHODS: The standard technique for transcervical recanalization was attempted in
      seven patients after failed reversal surgery and in 12 after failed tuboplasty.
      Four of seven patients with failed reversal surgery had fistular tracts and one
      also had a stricture; the remaining three patients and all 12 patients treated
      after failed tuboplasty and tube reimplantation had strictures at the site of
      implantation or anastomosis. RESULTS: Transcervical recanalization failed in all
      patients with fistulas but succeeded in 13 of 15 with stenoses. Three patients
      became pregnant 1-16 months after recanalization and two after in vitro
      fertilization and embryo transfer. Reocclusion occurred in two of 10 patients
      reexamined 6-36 months after recanalization. CONCLUSION: Transcervical
      recanalization is recommended as an alternative to repeat microsurgical
      reimplantation or tuboplasty.

PMID- 8153331
TI  - Use of iotrolan versus ethiodized poppy-seed oil in hysterosalpingography.
AB  - PURPOSE: To compare use of the water-soluble, nonionic isosmolar dimer iotrolan
      with that of ethiodized poppy-seed oil in hysterosalpingography with regard to
      side effects, diagnostic quality, and postexamination conception rates. MATERIALS
      AND METHODS: A prospective randomized design was used in a study of 245 patients.
      Questionnaires and patient records were used to acquire information. All
      examinations and ratings of diagnostic quality were performed by the same three
      investigators. Statistical calculations were performed with the chi 2 test,
      including the Mantel-Haenszel variant, and the Kruskal-Wallis test. RESULTS: No
      substantial differences between the contrast media could be detected concerning
      pain during the procedure, delayed pain, or postexamination bleeding.
      Visualization of the uterine cavity and ampullary rugae was markedly better with
      use of iotrolan. The postexamination conception rate was higher with use of
      ethiodized poppy-seed oil (24.0%) but was not significantly different
      statistically (P = .44) from that seen after use of iotrolan (19.8%). CONCLUSION:
      The authors believe the use of iotrolan is preferable to that of ethiodized poppy
      seed oil.

PMID- 8153332
TI  - Medical impact of unedited preliminary radiology reports.
AB  - PURPOSE: To determine the potential frequency of adverse patient outcomes
      resulting from erroneous preliminary radiology reports. MATERIALS AND METHODS:
      The authors determined the number of preliminary radiology reports that changed
      substantively between the preliminary and final version during a 10-day
      collection period. They analyzed 200 of 1,648 reports to determine the potential
      for adverse outcome. RESULTS: Only 5.6% of the preliminary radiology reports were
      changed substantively. Two percent of all reports contained changes that would
      have led to additional testing or treatment and, possibly, increased morbidity.
      CONCLUSION: Immediate electronic transfer of a preliminary radiology report
      results in a small but important number of adverse outcomes; however, if a final
      edited report follows within 24 hours and referring physicians are called
      whenever the preliminary report contains erroneous information, the benefits of
      rapid information transmission may outweigh the additional risks.

PMID- 8153333
TI  - Primary epiploic appendagitis: clinical, US, and CT findings in 14 cases.
AB  - PURPOSE: To describe the appearance at ultrasonography (US) of primary epiploic
      appendagitis in correlation with computed tomographic (CT) findings. MATERIALS
      AND METHODS: From January 1992 through June 1993, clinical, US, and CT findings
      were reviewed in 14 patients with primary epiploic appendagitis (seven men and
      seven women, aged 25-51 years [mean, 39 years 3 months]). Follow-up examinations
      were performed with US alone (n = 4), with US and CT (n = 3), and with clinical
      examination (n = 14). Surgery was performed in two patients. The main symptoms
      were right (n = 3) or left (n = 11) flank pain. RESULTS: US revealed an echogenic
      mass that was small, ovoid, and noncompressible, located anterolateral to the
      right colon (n = 3), anterior or anterolateral to the left colon (n = 10), and
      anteromedial to the left colon (n = 1). CT helped confirm the presence of a fatty
      lesion in each patient without other inflammatory process in the abdomen.
      Symptoms resolved within 7 days in 12 patients. CONCLUSION: Primary epiploic
      appendagitis has fairly characteristic US and CT features that enable a rapid
      diagnosis.

PMID- 8153334
TI  - Mucosal prolapse syndrome: diagnosis with endoscopic US.
AB  - PURPOSE: To determine the value of endoscopic ultrasound (US) in the diagnosis of
      mucosal prolapse syndrome (MPS), also known as solitary ulcer of the rectum.
      MATERIALS AND METHODS: Three male and two female patients (age range, 17-66
      years) with biopsy-proved MPS underwent endoscopic US. The average rectal wall
      thicknesses of the affected areas were compared with those of normal-appearing
      mucosa. RESULTS: The gross appearance of the rectal lesions was classified into
      three types: polypoid (n = 2), flat (n = 1), and ulcerative (n = 2). In all three
      types of lesions, endoscopic US demonstrated smooth, diffuse thickening of the
      third layer of the rectal wall; the other layers had minimal thickening. Neither
      a solid hypoechoic mass nor a transmural infiltrating lesion was visible, and the
      five-layer structure of the rectal wall was completely preserved. In the polypoid
      lesions, the third layer was winding as well as thickened, and microcystic
      components were occasionally found. CONCLUSION: Endoscopic US enabled
      differentiation of MPS from other conditions such as malignant neoplasia and
      Crohn disease.

PMID- 8153335
TI  - CT findings in hepatocellular carcinoma: correlation of tumor characteristics
      with causative factors, tumor size, and histologic tumor grade.
AB  - PURPOSE: To determine computed tomographic (CT) findings of hepatocellular
      carcinoma (HCC) in a predominantly non-Asian population and to assess any
      morphologic differences with respect to causative factors, tumor size, and
      histologic grade. MATERIALS AND METHODS: Clinical history, pathology reports,
      histologic specimens, and CT findings in 100 patients with HCC were reviewed. All
      patients underwent contrast material-enhanced incremental dynamic CT. Findings
      were agreed on by consensus. RESULTS: The mosaic pattern was seen in 46% of
      cases, venous invasion in 33%, and tumor encapsulation in 31%; frequencies were
      similar to those reported with Asian patients. A mosaic pattern was more common
      in patients with larger tumors (P = .036). Venous invasion was more common in
      patients with alcohol-induced cirrhosis (P = .003) and in those with higher grade
      tumors (P = .043). Tumor encapsulation was more common in patients with lower
      grade tumors (P = .012). CONCLUSION: Reported morphologic differences between non
      Asian and Asian patients with HCC may be due to differences in underlying liver
      disease, tumor size, and histologic grade.

PMID- 8153336
TI  - Infectious liver foci in leukemia: comparison of short-inversion-time inversion
      recovery, T1-weighted spin-echo, and dynamic gadolinium-enhanced MR imaging.
AB  - PURPOSE: To assess the performances of three different magnetic resonance (MR)
      imaging techniques in the evaluation of patients with leukemia and suspected
      hepatic candidiasis. MATERIALS AND METHODS: Twelve patients with acute leukemia
      and definite or clinically suspected hepatic candidiasis were imaged at 1.0 T
      with a T1-weighted spin-echo (SE) technique, a short-inversion-time inversion
      recovery (STIR) fat-suppression technique, and a dynamic gadolinium-enhanced fast
      low-angle shot (FLASH) technique. The conspicuity of hepatic lesions was
      evaluated semiquantitatively and ranked on a three-point scale. RESULTS: Multiple
      liver lesions were seen as high-signal-intensity foci with the STIR sequence;
      other sequences showed equivocal results. In the semiquantitative evaluation,
      STIR was significantly (P < .001) superior to both T1-weighted SE and contrast
      enhanced FLASH techniques. Multiple red blood cell transfusions affected lesion
      conspicuity. CONCLUSION: STIR imaging is recommended as the MR technique of
      choice at 1.0 T in the evaluation of infectious liver foci in patients with acute
      leukemia.

PMID- 8153337
TI  - Perianal fistulas: use of MR imaging for diagnosis.
AB  - PURPOSE: To evaluate use of magnetic resonance (MR) imaging with saline solution
      as contrast agent in diagnosis of perianal fistulous disease. MATERIALS AND
      METHODS: Spin-echo intermediate-, T2-, and T1-weighted images were obtained
      before and after instillation of saline solution into anal fistulas in 12 of 16
      consecutive patients. In four patients without secretory fistulas, images were
      obtained without contrast enhancement. RESULTS: Fistulous tracts were found in 13
      patients, fluid cavities in 13, secondary fibrotic tracts in two, and normal
      perirectal tissue in one. The extent of fistulas and fluid collections was better
      delineated or more conspicuous on contrast-enhanced images in eight and 10
      examinations, respectively, in part due to expansion of collapsed portions of the
      fistulous system. T2-weighted images were sufficient for diagnosis. CONCLUSION:
      MR imaging with saline solution as contrast agent may improve visualization of
      fistulas and their relationship to normal anatomic structures in patients with
      complex fistulous systems with relatively sparse secretion.

PMID- 8153338
TI  - Reversal of insulin-dependent diabetes mellitus after percutaneous pancreatic
      pseudocyst drainage.
AB  - A 75-year-old man achieved complete reversal of insulin-dependent diabetes
      mellitus after percutaneous, computed tomography-guided, pancreatic pseudocyst
      drainage. This reversal is believed to have resulted from removal of physiologic
      stress after drainage. This and previously reported cases of new-onset diabetes
      following this procedure suggest close serum glucose monitoring in all patients
      undergoing percutaneous pancreatic pseudocyst drainage.

PMID- 8153340
TI  - Appendicitis: efficacy of color Doppler sonography.
AB  - PURPOSE: To determine whether the addition of color Doppler ultrasonography (US)
      to gray-scale US can help diagnose appendicitis in children. MATERIALS AND
      METHODS: One hundred children with suspected appendicitis were evaluated with
      gray-scale and color Doppler US scanning. Color Doppler US scans were considered
      positive for appendicitis if increased vascularity was demonstrated in the
      appendiceal wall and positive for perforation with abscess if a hyperemic right
      lower quadrant mass was seen. Gray-scale US was positive for appendicitis if a
      blind-ending, noncompressible appendix larger than 6 mm in diameter, a loculated
      periappendiceal mass, or both were identified. RESULTS: Thirty-nine patients had
      acute appendicitis; 26 had uncomplicated appendicitis, and 13 had perforation.
      Acute appendicitis was identified in 34 of 39 patients (87%) on color Doppler US
      scans with a sensitivity of 87%, specificity of 97%, and accuracy of 93%. Gray
      scale US sensitivity was 87%; specificity, 92%; and accuracy, 90%. CONCLUSION:
      Blood flow in the appendiceal wall or right lower quadrant mass on color Doppler
      US scans suggests appendicitis, but absence of flow cannot definitively
      distinguish a normal from an abnormal appendix.

PMID- 8153339
TI  - Defecography in multiple sclerosis patients with severe constipation.
AB  - PURPOSE: To evaluate defecography in assessment of anorectal function in patients
      with multiple sclerosis (MS) who have intractable constipation. MATERIALS AND
      METHODS: Eleven patients with MS and constipation (10 women, one man) underwent
      defecography. A total of 130 mL of barium, liquid (20 mL) and paste, was
      introduced into the rectum. A dab of barium marked the external anal orifice,
      and, in the women, a tampon soaked with contrast medium marked the vagina. Video
      radiographic images and supplemental 100-mm static camera images were obtained.
      RESULTS: During defecation, six patients had no puborectalis muscle effacement,
      four patients had partial effacement, and one patient had complete effacement. No
      rectal emptying occurred in five patients, and emptying was incomplete in the
      rest. Three patients developed an intussusception, and two developed a
      posterolateral pouch. CONCLUSION: Defecography readily demonstrates rectal outlet
      obstruction and the failure of the puborectalis and anal sphincter muscles to
      relax. These are frequent findings in MS patients with intractable constipation.

PMID- 8153341
TI  - Pediatric testicular tumors: evaluation with gray-scale and color Doppler US.
AB  - PURPOSE: To evaluate the appearance of testicular neoplasms in pediatric patients
      at examination with gray-scale and color Doppler ultrasonography (US). MATERIALS
      AND METHODS: Gray-scale and color Doppler US were performed in seven patients
      aged 8 1/2 months to 17 years 6 months (mean age, 7.8 years) with testicular
      neoplasms proved at histologic examination. Gray-scale images were evaluated for
      echogenicity and presence of testicular masses; color Doppler US was used to
      assess the presence and distribution of color flow. RESULTS: Gray-scale US showed
      enlargement of the affected testis in all patients. Testicular echogenicity was
      normal in four prepubertal patients; discrete masses were seen in all three
      postpubertal patients. The gray-scale findings correlated with patient age. Color
      Doppler US demonstrated increased blood flow in six of seven testicular
      neoplasms. Three of the four patients with normal gray-scale echogenicity had
      diffuse hypervascularity and one had a focal hypervascular mass on color Doppler
      scans. CONCLUSION: Color Doppler US is more helpful than gray-scale US in
      identification of testicular tumor.

PMID- 8153342
TI  - Left-sided esophageal indentation in right aortic arch with aberrant left
      subclavian artery.
AB  - PURPOSE: To determine the structures responsible for the left-sided indentation
      in right aortic arch (RAA) with aberrant left subclavian artery (ALSA). MATERIALS
      AND METHODS: Magnetic resonance (MR) imaging was performed in five patients with
      RAA with ALSA in whom barium esophagography demonstrated a left-sided defect at
      the level of the aortic arch. RESULTS: In four patients, the aortic diverticulum
      (dorsal aortic root remnant) extended to the left of the esophagus, explaining
      the left-sided indentation. In one of those four patients, the ALSA contributed
      to this defect. In only one patient was no patent vascular structure identified
      to the left of the esophagus, and it was assumed that the ligamentum arteriosum
      alone produced this defect. CONCLUSION: The aortic diverticulum appears to be an
      important factor in the production of the left-sided esophageal defect in
      patients with RAA with ALSA.

PMID- 8153343
TI  - Cancer of the anal canal: treatment with chemotherapy and low-dose radiation
      therapy.
AB  - PURPOSE: To determine the efficacy of a standardized protocol of chemotherapy and
      low-dose radiation therapy in treatment of patients with anal canal cancer.
      MATERIALS AND METHODS: Forty-two consecutive patients with anal canal cancer were
      treated with 15 fractions of 30-Gy photon beam radiation therapy administered
      anteroposterior-posteroanterior in conjunction with chemotherapy with 5
      fluorouracil and mitomycin C. Survival analysis was performed with the lifetest
      procedure. RESULTS: In patients with stage T1 and T2 tumors, 26 of 29 (90%) were
      free of disease after chemotherapy and radiation therapy and had no recurrent
      tumors. In patients with stage T3 and T4 tumors, five of 13 (38%) were free of
      disease after therapy and had no recurrences. CONCLUSION: This therapy is
      effective for epidermoid cancers of the anal canal that are smaller than 5 cm
      regardless of nodal status. Tumors larger than this or that invade adjacent
      structures are not adequately controlled with this protocol.

PMID- 8153344
TI  - Small bowel biopsy through an enteroclysis catheter to augment findings at
      enteroclysis and hypotonic duodenography.
AB  - Proximal jejunal mucosal biopsy was performed by a radiologist through the
      nasojejunal catheter at the time of enteroclysis. Seventeen patients (10 men and
      seven women, aged 23-73 years [mean, 46 years]) were studied with enteroclysis
      because of clinical signs of malabsorption with suspected small bowel disease. In
      seven (41%) patients, results at biopsy were positive, and results in another
      seven (41%) were positive at enteroclysis. In 10 (59%) patients, results were
      positive at one or both tests. Performance of both small bowel biopsy and
      enteroclysis at the same session is feasible and offers additional clinically
      pertinent information than can be obtained at enteroclysis alone.

PMID- 8153345
TI  - Linguine sign at MR imaging: does it represent the collapsed silicone implant
      shell?
AB  - One intact and one ruptured single-lumen implant were surgically placed in a
      rabbit. Magnetic resonance (MR) imaging was performed before and after surgical
      removal, and the ruptured implant was imaged after removal of the implant shell.
      Multiple curvilinear hypointense lines (linguine sign) were present in the MR
      images of the ruptured implant and of the implant shell alone immersed in saline
      solution but not in the image of the free silicone. The collapsed implant shell
      in a ruptured silicone implant does cause the linguine sign.

PMID- 8153346
TI  - Tongue displacement: visualization with rapid tagged magnetization-prepared MR
      imaging.
AB  - The authors describe a technique to depict tongue muscle displacement with tagged
      magnetization-prepared gradient-recalled echo magnetic resonance imaging. Three
      Japanese volunteers (three men, aged 31-36 years) were studied while they
      articulated specific sounds. Each image was obtained in less than 2 seconds
      without need for gating. Displacement and alteration of the tags within the
      tongue muscle during phonation were clearly visible. The technique may prove
      useful in the study of phoniatric pathophysiology.

PMID- 8153347
TI  - Pelvic mass: CT-guided interstitial catheter implantation with high-dose-rate
      remote afterloader.
AB  - A technique is presented for computed tomography (CT)-guided interstitial
      catheter placement and treatment planning for high-dose-rate brachytherapy. In a
      66-year-old woman with adenocarcinoma of unknown origin that had metastasized to
      the right ilium, interstitial brachytherapy catheters were placed by means of CT
      guidance. With use of a treatment planning system with dose optimization, an
      excellent dose distribution was obtained with minimal dose being delivered to the
      surrounding critical tissues. For selected patients, this procedure can provide
      effective and safe local treatment for solid tumors.

PMID- 8153348
TI  - Safety of MR contrast media.

PMID- 8153349
TI  - To tilt or not to tilt?

PMID- 8153350
TI  - [Use of cheese whey for growing the Bradyrhizobium japonicum E-109 strain].
AB  - The growth of Bradyrhizobium japonicum E-109 using cheese whey as carbon source
      was studied. The cheese whey was previously hydrolyzed by acid or enzymatic
      treatment with purified beta galactosidase or a crude extract from Kluyveromyces
      fragilis. The results obtained demonstrated that the use of the modified
      enzymatic hydrolyzed whey as carbon source allowed the growth of B. japonicum E
      109 reaching a concentration of approximately 10(10) viable cells/ml. These
      results are considered of industrial value because the poluent power whey is
      greatly reduced.

PMID- 8153351
TI  - [Taxonomic aspects of strains from Patagonia and type strains of Desulfovibrio].
AB  - Fourteen type strains and 42 indigenous strains of Desulfovibrio were studied and
      taxonomic numeric methods were applied (Cluster Analysis, Principal Coordinates
      Analysis, Correspondence Analysis). The type strains as well as the indigenous
      ones share a low quantity of carbon and energy sources. Type strains have a
      taxonomic structure which shows net clusters; indigenous strains possess a
      grading (or "adjustment") in their positive reactions hence the taxonomic
      structure is not so clear. Both classifications are firm since they suffer
      minimal changes when they are joined.

PMID- 8153353
TI  - [Cap-independent mechanism of translation initiation in eukaryotes].

PMID- 8153352
TI  - [Presence of antibodies against Venezuelan equine encephalitis virus subtype VI
      in patients with acute febrile illness].
AB  - In Argentina, there is no record of human cases produced by Dengue virus
      (Flavivirus), but Paraguay and Brasil (neighbouring countries) have notified
      human outbreaks of Dengue Haemorrhagic Fever. In this report, we inform the
      serological results of a limited human outbreak of a Dengue-like acute illness
      that occurred in General Belgrano Island, Formosa, Argentina in April 1989. This
      island is 35 km far from Clorinda city of Paraguay river, with a human population
      of 150 inhabitants. The weather of this area is humid with abundant rainfall,
      favouring mosquitoes proliferation. Two samples of serum from 28 human notified
      cases were studied using hemagglutination inhibition test (HI), complement
      fixation (CF), and plaque reduction neutralization (NT) test in Vero cell
      cultures. All tested sera were negative to Dengue, St. Louis encephalitis, Yellow
      Fever, Bussuquara, Rocio, Eastern and Western Equine Encephalitis arboviruses as
      well as Influenza and Rubella viruses. By contrast, infection with Venezuelan
      equine encephalitis virus (VEE), subtype VI-AG80-663 strain was demonstrated
      (34.5% positive by HI, 39.1% by CF and 51.6% by NT). Seroconversion was detected
      by NT in six cases and only five were positive by CF. The 26.8% of the sera
      reacted also with VEE subtype I AB by NT. Considering that no cross reaction were
      detected in NT with these two subtypes, our results suggest that both viruses are
      concomitantly circulating in the studied area. Furthermore, the seroconversions
      detected with AG80-663 strain firmly indicate that during the outbreak this virus
      subtype was circulating in the island, although we could not assure that it was
      the causal agent of the acute disease.

PMID- 8153354
TI  - [Actin-binding proteins and cell growth control].

PMID- 8153355
TI  - [The photorepair of pyrimidine dimers by DNA photolyase].

PMID- 8153356
TI  - [Supramolecular assembly of a membrane protein--hollow spheres of
      bacteriorhodopsin in its three-dimensional crystal].

PMID- 8153357
TI  - [Denitrification by fungi and cytochrome P-450 nor].

PMID- 8153358
TI  - [The current view of molecular biology of DNA tumor virus].

PMID- 8153359
TI  - [Nanobiology of muscular contraction].

PMID- 8153360
TI  - [Cytokine signal transduction and expression of cell cycle related genes].

PMID- 8153361
TI  - [Freud's identification with men who had 2 mothers: Oedipus, Leonardo da Vinci,
      Michealangelo and Moses].
AB  - In view of the fact that as a child Sigmund Freud was looked after by two mothers
      -his actual mother and a nursemaid--it is hardly surprising that traces of this
      pre-oedipal situation, fraught as it was with traumatisation and loss, should be
      discernible in the works of the creator of psychoanalysis. Freud's continued
      preoccupation with the Oedipus myth, his interest in "great men" like da Vinci
      and Michelangelo, and finally his identification with the figure of Moses are
      pointers not only to the paternal dimension (as long suggested by Freud's
      biographers) but also to the maternal dimension and its significance for Freud's
      life and work. The author demonstrates that those mythical and historical figures
      which Freud identified with--Oedipus, da Vinci, Michelangelo, Moses--themselves
      all had two mothers and sublimated this traumatic experience into outstanding
      achievements, the same being true of Freud himself "who solved the famous riddle
      and was a most powerful man".

PMID- 8153362
TI  - [A single "principle" question: Gisela Fluss and Ichthyosaura. A marginal note on
      Freud's early letters].
AB  - Freud's biographers have hitherto proceeded on the assumption that his youthful
      love Gisela Fluss and the figure of "Ichthyosaura" that makes its appearance in
      his correspondence of the same period were one and the same person. The author
      demonstrates that they must in fact have been two different women.

PMID- 8153363
TI  - [The legacy of Sandor Ferenczis].

PMID- 8153364
TI  - [The fate of Freud's early mother-child relations].

PMID- 8153365
TI  - A case with Cushing's syndrome treated with arterial ablation of adrenal gland by
      absolute ethanol.
AB  - Adrenal arterial embolization with absolute ethanol was performed for the
      treatment of Cushing's syndrome. A 55-year-old woman was admitted to our hospital
      with complaints of obesity, hypertension, and back pain caused by left adrenal
      hyperplasia after surgical resection of the right adrenal gland. Therapeutic
      adrenal arterial embolization was performed by the coaxial technique using
      absolute ethanol (AE) as an embolic material. No severe complications were
      encountered during the procedure, and the patient was discharged without symptoms
      or abnormalities on laboratory tests.

PMID- 8153366
TI  - Expandable metallic stent placement in the tracheobronchial tree in dogs.
AB  - Expandable metallic stents (Gianturco zig-zag wire stents) of various sizes were
      placed in the trachea of eight dogs to establish conditions suitable for
      endotracheal wire stent placement. Stents of 3.0 cm in diameter and 2, 3, or 4 cm
      in length were constructed with 0.018, 0.016, or 0.013 inch stainless steel wire.
      Optimal dilatation of the trachea was attained with stents 2 cm long made of
      0.013 and 0.016 inch wire, and their surface became covered with ciliated
      columnar epithelium. In contrast, stents with stronger expansive force, such as
      those 2 cm long made of 0.018 inch wire, became deeply embedded in the membranous
      portion of the trachea. With stents of little expansive force, such as those 3 or
      4 cm long, dilatation of the trachea was inadequate regardless of the caliber of
      the wire, and consequently these stents were not completely covered with
      epithelium. The results of the study suggest the therapeutic potential of
      expandable metallic stents for clinical treatment of patients with
      tracheobronchial stenosis.

PMID- 8153367
TI  - High-dose rate intracavitary therapy for cervical cancer with a microSelectron: a
      preliminary report.
AB  - Our early experience using microSelectron HDR to treat cervical cancer patients
      at Osaka University Hospital is presented. From June 1991 through December 1992,
      a total of 20 patients (stage Ib, 6; stage IIa, 2; stage IIb, 5; stage IIIb, 6
      and stage IVa, 1) with previously untreated invasive uterine cervical cancer and
      intact uterus were treated with high-dose rate intracavitary therapy administered
      with a microSelectron. For the treatment, a standard rigid applicator made of
      stainless steel for a microSelectron was used. Twenty to 30 Gy of external
      irradiation was administered to the whole pelvic field and 30 to 20 Gy to the
      central shielded field (total 50 Gy/5-6 weeks) for patients in stage II-IVa. For
      stage Ib, 40 Gy was delivered to the central shielded field. The 192Ir source had
      an activity of 370 GBq as of the measuring time. Source loading corresponded to
      the Manchester System for cervical cancer. Thirty-two or 30 Gy was administered
      at point A in four fractions over four weeks of intracavitary irradiation. Early
      primary tumor responses for all patients were complete. There have been two local
      recurrences in stage IIb and IIIb patients. Three patients in stages Ib, IIb, and
      IIIb developed para-aortic lymph node metastases, and two of them died from
      generalized metastasis. No acute radiation injury has been observed. One patient
      in stage IIb developed subileus five months after irradiation. From our early
      experience, it is concluded that microSelectron HDR can be used for cervical
      cancer patients as safely and effectively as our previously used high-dose rate
      machine.

PMID- 8153368
TI  - Mid-dose rate intracavitary therapy for cervical cancer with a Selectron: a
      preliminary report.
AB  - Our early experience with Selectron MDR in treating cervical cancer patients at
      Osaka University Hospital is presented. From May 1991 through December 1992, a
      total of 22 patients (stage Ia, 1; stage Ib, 3; stage IIa, 1; stage IIb, 2; stage
      IIIb, 13 and stage IVa, 2) with previously untreated uterine cervical cancer and
      intact uterus were treated with mid-dose rate intracavitary therapy administered
      with a Selectron. A rigid applicator made of stainless steel for the Selectron
      was used for the treatment. The 137Cs source had an activity of 1.48 GBq as of
      reference time. Source loading corresponded to the Manchester System. Early tumor
      responses for all patients were complete. No acute radiation injury has been
      observed. There have been two local recurrences in stage IIIb patients. One of
      them developed para-aortic lymph node metastasis and died from distant
      metastasis. Another patient in stage IIIb had para-aortic and left
      supraclavicular lymph node metastasis and died from distant metastasis. Four
      patients developed rectal bleeding (grade 1, 3; grade 3, 1). One of them had been
      treated for aplastic anemia with steroid. The cause of grade 3 rectal bleeding
      was considered to be technical failure in intracavitary application. The
      remaining two patients recovered without treatment. From our early experience, it
      is concluded that Selectron MDR can be used for cervical cancer patients as
      safely and effectively as our previously used high-dose rate machine.

PMID- 8153369
TI  - Scintigraphic study on the distribution of radiolabeled cis
      diamminedichloroplatinum (II) in the tumor-bearing rabbit: a comparison between
      intra-arterial injection with lipiodol and intravenous injection.
AB  - To compare the distribution of cis-diamminedichloroplatinum (II) (CDDP) on
      scintigraphic images between intra-arterial injection with lipiodol and
      intravenous injection, we obtained serial scintigraphic images using radiolabeled
      CDDP (Pt-195m CDDP), which had a high specific activity (7.4 x 10(6) Bq [200
      microCi]/mg-CDDP), in the rabbit VX-2 tumor system. A dose of 9.25 x 10(6) Bq
      (250 microCi) of Pt-195m CDDP was injected at one shot via an ear vein, while 7.4
      x 10(6) Bq (200 microCi of Pt-195m CDDP mixed with 1 ml of lipiodol was injected
      at one shot via a saphenous artery. Mean pixel count, which was corrected for the
      total dose injected, in the arterially injected tumor always exceeded than that
      in the intravenously injected tumor. Pt-195m CDDP uptake by the rabbit tumor at 2
      hr was 7.8% of the total injected dose with intravenous injection and 16.0% with
      intra-arterial injection. These data suggest that intra-arterial injection with
      lipiodol is a more useful method to increase CDDP uptake by tumors than intra
      venous injection.

PMID- 8153370
TI  - Aneurysm arising from the petrous portion of the internal carotid artery: case
      report.
AB  - A 21-year-old man with hearing loss and recurrent otorrhagia was shown
      angiographically to have an aneurysm arising from the intrapetrous internal
      carotid artery (ICA). Endovascular balloon occlusion of the aneurysm with
      preservation of the parent ICA was attempted twice, but each time the balloon
      deflated and the aneurysm reappeared two weeks and three months, respectively,
      following the endovascular procedures. The patient was then successfully treated
      with a surgical trapping procedure combined with superficial temporal artery
      middle cerebral artery bypass.

PMID- 8153371
TI  - Successful therapeutic embolization of aldosteronoma using absolute ethanol.
AB  - Adrenal arterial infusion of absolute ethanol (AE) was successfully performed to
      treat a hyperfunctioning aldosteronoma. One milliliter of AE was infused into the
      branches of the inferior adrenal artery using a microcatheter with coaxial
      technique. No severe complications occurred during the procedure. The patient has
      experienced no recurrence of symptoms, and laboratory values have remained normal
      for eight months after therapy.

PMID- 8153372
TI  - An autopsy case: limited small cell lung cancer controlled with radiation therapy
      alone.
AB  - We report a patient with limited small cell lung cancer treated with radiation
      therapy alone, who survived more than two years. At autopsy no residual tumor or
      metastasis was found. This case can be of help in estimating the value of
      thoracic irradiation for local control of tumor, which is still a subject of
      controversy.

PMID- 8153373
TI  - MR imaging of acute disseminating encephalomyelitis.
AB  - We present a case of acute disseminating encephalomyelitis (ADEM) diagnosed on MR
      imaging. MR imaging accurately identified the location of the ADEM lesions in the
      spinal cord and brain.

PMID- 8153374
TI  - Tumour stem cells: the biological concept and its application in cancer
      treatment.
AB  - Experiments in different transplantable mouse tumours suggest that a proportion
      ranging from 0.1% to 100% of all tumour cells in these different tumours meet the
      functional definition criteria of tumour stem cells, i.e. regrowth of the tumour
      proceeded by clonal expansion from a single cell with unlimited proliferative
      potential. It is concluded that the proliferative organization of many or most
      human tumours may resemble that of the tissue of origin with a small proportion
      of stem cells and the majority of transit cells, both proliferating or resting.
      Cell loss and accelerated repopulation are due to regulated changes in the
      symmetry constraint of stem cell divisions.

PMID- 8153375
TI  - Tumour stem cells: the relevance of predictive assays for tumour control after
      radiotherapy.

PMID- 8153376
TI  - Radiation-induced injury to the visual pathway.
AB  - Radiation-induced injury to the visual pathway was reviewed in a cohort of
      patients treated for various cancers of the nasal cavity and paranasal sinuses
      between 1969 and 1985. The study subjects consisted of 219 patients, 137 men and
      82 women, in whom detailed records were available on the extent of orbital
      shielding, treatment plan for estimating doses delivered to various optic
      structures, and visual acuity follow-up information. There was a wide range in
      doses administered to various optic structures because patients with different
      primary lesion types were included and the radiotherapy techniques used varied
      during this era. The endpoint of the study was visual acuity < 20/100. The Cox
      proportional hazard model was used to assess the influence of various factors on
      the latent time to visual impairment and to fit the LQ model to the failure-time
      data. Actuarial curves showing the proportion of patients with visual impairment
      as a function of dose and time were generated. Corneal injury occurred in 24 of
      the 49 patients treated with the 3-field technique without any orbital shielding;
      variables affecting the incidence of cornea injury were total radiation dose and
      chemotherapy. Symptomatic retinopathy was diagnosed in 7 of 77 patients who
      received irradiation to a relatively large retinal surface, but no variables were
      found to correlate with this complication. Eight patients developed ipsilateral
      blindness due to optic neuropathy and 11 patients had bilateral visual impairment
      secondary to chiasm injury. The total radiation dose was identified as the
      predominant determinant. None of patients receiving a dose of < 50 Gy developed
      optic neuropathy or chiasm injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153377
TI  - The early changes in salivary gland function during and after radiotherapy given
      for head and neck cancer.
AB  - The salivary gland function of 47 patients treated by radical radiotherapy (CHART
      or conventionally fractionated treatment) for head and neck cancer has been
      studied before, during and for up to 12 weeks from the start of treatment.
      Pronounced falls in salivary flow and pH are seen once radiotherapy has
      commenced, particularly when both parotid glands are included in the treatment
      volume. The initial rate of reduction in flow reflects the rate of delivery of
      treatment. The parotid glands show the greatest sensitivity to radiotherapy
      compared with the other salivary glands and reduction in salivary flow is
      dependent on both dose and the proportion of the gland included in the treatment
      volume. These early changes in salivary gland function are as marked for patients
      receiving either CHART or conventionally fractionated treatment, so differing
      from the late changes which have been shown to be less evident after CHART.

PMID- 8153378
TI  - The effect of pulmonary function of local and loco-regional irradiation for
      breast cancer.
AB  - Eighty-five patients treated with loco-regional radiotherapy to the breast/chest
      wall and cervico-axillary nodes, and 16 patients treated with local radiotherapy
      to the breast/chest wall alone for breast cancer were enrolled in a prospective
      study to measure the effects of treatment on pulmonary function during the acute
      phase (10 weeks after completing irradiation) and during the late phase (12
      months after completing irradiation). Baseline pulmonary function values were
      obtained from all patients immediately prior to commencing radiotherapy. Twenty
      two patients (25.8%) treated with loco-regional radiotherapy developed transient
      chest symptoms compared with two patients (12.5%) treated with local radiotherapy
      (P = 0.11). Patients undergoing loco-regional radiotherapy showed a reduction of
      mean vital capacity of 0.13 litres (4.2%) (P < 0.0001) during the acute phase and
      at  1 year a further decrease occurred (P = 0.02) so that mean vital capacity was
      reduced by 0.18 litres (5.8%) (P < 0.0001) compared to pretreatment values. Mean
      transfer factor for carbon monoxide (TLCO) was reduced by 0.85 mmol.kPa-1.min-1
      [11.9%] (P < 0.0001) during the acute phase and remained unchanged at 1 year.
      Patients undergoing local radiotherapy to the breast/chest wall alone did not
      show any significant loss of vital capacity but mean TLCO was reduced during the
      acute phase by 0.65 mmol.kPa-1.min-1 (8.3%) (P < 0.002) which remained unchanged
      at 1 year. No significant association was found between impairment of ventilation
      or gas transfer and respiratory history, smoking history, concurrent respiratory
      symptoms, age, side treated or physiological pulmonary function in either the
      acute or late phase. This study has quantified some of the physiological sequelae
      following local and loco-regional radiotherapy for breast cancer. There is no
      evidence to suggest that any of the above factors are relevant to deciding which
      patients should, or should not, be offered local or loco-regional radiotherapy
      for breast cancer.

PMID- 8153379
TI  - Cardiac lesions after mediastinal irradiation for Hodgkin's disease.
AB  - We analysed the risk of myocardial infarctions in 339 patients with Hodgkin's
      disease treated with radiotherapy (rt) with or without chemotherapy. A total of
      112 patients underwent cardiac testing with echocardiography, rest and exercise
      electrocardiogram and myocardial scintigraphy. Nearly all patients have been
      treated with < 2.0 Gy per fraction to the anterior cardiac region. A
      significantly increased risk of myocardial infarctions or of sudden death has
      been observed (10 patients). No cardia events have been observed in 215 non
      smokers without hypertension and without coronary artery disease (CAD) already
      present before rt. In the heart study group (112 patients), there were 6 patients
      with probable or proven CAD. Five of these 6 patients had known risk factors for
      CAD. Echocardiography showed sclerosis of the aortic and or the mitral valves in
      34 patients. Of these patients, 2 had a slight and 1 a moderate aortic stenosis,
      5 had a slight and 1 a moderate mitral regurgitation. Evidence for a disturbance
      of the diastolic function has not been observed. No patient had a clinically
      relevant pericardial lesion. In patients without risk factors for CAD, there is
      only a low risk of ischaemic cardiac events after modern mediastinal rt for
      Hodgkin's disease. Patients should eliminate the known risk factors. There is a
      high incidence of sclerosis of the mitral and or the aortic valves developing
      into clinically important lesions in few patients. Decision on the treatment
      strategy and the rt technique should also involve consideration of the cardiac
      risk. For routine follow-up, we recommend inclusion of an echocardiography in
      intervals between 3 and 4 years.

PMID- 8153380
TI  - Secondary solid malignant tumors occurring after bone marrow transplantation for
      severe aplastic anemia given thoraco-abdominal irradiation.
AB  - PURPOSE: We have evaluated irradiation doses received at location of secondary
      solid tumors occurring after bone marrow transplantation (BMT) in five of 147
      patients grafted for severe aplastic anaemia. RESULTS: All 5 tumors occurred
      within the radiation field penumbra. The estimated received dose varied from 6 Gy
      for one inner field secondary tumor, to 2.5 Gy for the remaining secondary
      tumors. CONCLUSION: Tumors may arise in the zone where the delivered radiation
      dose drops dramatically. Irradiation, with associated cofactors, may promote the
      development of epidermoid carcinoma in irradiated patients for BMT.

PMID- 8153381
TI  - The influence of tumour temperature on ischemia-induced cell death: potential
      implications for the evaluation of vascular mediated therapies.
AB  - We have evaluated the influence of tumour temperature on the kinetics and extent
      of tumour cell death following induction of ischemia. Induction of ischemia in
      SCCVII tumours implanted subcutaneously in the back of syngeneic C3H mice results
      in a rapid cooling of the tumour from a resting value of 35.2 degrees C, towards
      ambient temperature. In the SCCVII tumour no significant cell kill is detected in
      the first hour of ischemia. At longer times cell kill was detected and a survival
      level of 2 x 10(-2) was attained after 6 h of ischemia. However, if the tumours
      were maintained at a temperature of 37 degrees C following induction of ischemia
      a more rapid and dramatic reduction in cell survival is observed with a survival
      level of approximately 10(-5) being attained after 4 h of ischemia. Qualitatively
      similar results are obtained using the Lewis lung tumour implanted in C57BL mice.
      Similar rapid cooling following occlusion of the blood supply is observed in the
      C3H/TIF tumour implanted in the foot. For the C3H/TIF induction of ischemia for
      up to 6 h resulted in no significant growth delay provided the tumours were kept
      at room temperature. However, if the tumours were maintained at a temperature of
      37 degrees C during the ischemic insult significant growth delay was observed for
      all clamping times exceeding 1 h. These results show the importance of tumour
      temperature on the kinetics and extent of tumour cell kill during ischemia. This
      finding has particular relevance for studies in which agents known to reduce
      tumour blood flow are used in animals bearing superficially located tumours.

PMID- 8153382
TI  - Tumour stem cells: facts, interpretation and consequences.

PMID- 8153383
TI  - Wedge factor constituents of high energy photon beams: field size and depth
      dependence.
AB  - Wedge factors have been determined as a function of field size and phantom depth
      for a 60Co gamma-ray beam and X-ray beams in the range from 4 MV to 25 MV. The
      results show an increase of the wedge factor with field size, up to 9.1% for the
      25 MV X-ray beam. The magnitude of this increase is a linear function of the
      product of that part of the irradiated wedge volume that can be observed from the
      point of measurement, its mass energy-absorption coefficient and mass density.
      This relationship is independent of the photon beam energy, the type of wedge
      material and the wedge angle. Differences in variation of the amount of
      backscatter to the monitor with field size for the open and wedged photon beam
      yielded only a minor influence, up to 0.7%. For the 4-16 MV X-ray beams the wedge
      factor increases linearly with phantom depth, almost independently of field size.
      For the 60Co gamma-ray beam and the 25 MV X-ray beam the wedge factor variation
      is a more complicated function of phantom depth for a particular field size.

PMID- 8153384
TI  - Quality assurance of the simultaneous boost technique for prostatic cancer:
      dosimetric aspects.
AB  - Quality assurance (QA) in radiotherapy is of particular importance if a new
      irradiation technique is introduced. The dosimetric aspects of such a QA program
      concern the check of the dose calculation procedure, i.e. the prediction of the
      relative dose distribution, as well as the verification of the absolute value of
      the target absorbed dose specified at a particular point. In our institution a QA
      program has been developed for a new conformal irradiation technique of prostatic
      cancer: the simultaneous boost technique. With this technique the dose of the
      boost field and the large field are given simultaneously, using customized 10 mm
      thick Roses-metal plates in which the boost field has been cut out. The
      computation of the dose distribution, using a procedure adapted from a
      commercially available 2D treatment planning system, has been compared with
      isodose distributions measured in a water phantom. Good agreement, better than 3%
      or 3 mm, was observed for both open and wedged 8 MV X-ray beams. In vivo dose
      measurements have been performed on individual patients to check the dose
      delivery at the specification point. An agreement better than +/- 2% with the
      calculated dose value was required. The average ratio for 18 patients of the
      actual and expected dose value amounted to 1.005 +/- 0.017 (1 SD) after a
      correction of the number of monitor units for 2 patients during the treatment.
      Quality control of the dose transmission factor of the Roses-metal plates has
      been performed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153385
TI  - The relative cellular radiosensitivity of 30 human in vitro cell lines of
      different histological type to high LET 62.5 MeV (p-->Be+) fast neutrons and 4
      MeV photons.
AB  - It has been suggested that fast neutron therapy may have a role in the treatment
      of those tumours which lie within the most photon-resistant histological
      categories. A clinical radiobiological study by Battermann et al., however, did
      not support this hypothesis (Battermann, J.J. et al., Eur. J. Cancer 17: 539-548,
      1981). Similarly, in a comparison of the intrinsic cellular radiosensitivity of
      20 human in vitro cell lines with 4 MeV photons and 62.5 MeV (p-->Be+) neutrons,
      there was no correlation between RBE and photon sensitivity. However, because the
      range of histological cell types in this in vitro study did not include
      sufficient representatives of the most sensitive and resistant histological
      categories, it was not possible to examine the relationship between histology and
      the relative efficacy of fast neutrons compared with photons. The intrinsic
      radiosensitivity of a further 10 human in vitro cell lines has thus been measured
      and the results of all 30 cell lines used in a comparison of the relationship
      between relative neutron sensitivity and histology. These results together with
      those obtained by reanalysis of published data from a clinical study of the RBE
      of pulmonary metastases by Battermann et al. suggest that in the clinical
      situation, photon-resistant histology per se may not be a sufficient criterion
      for the choice of high LET irradiation and emphasize the need for predictive
      assays for individual tumours.

PMID- 8153386
TI  - Steepness of dose-response curve for larynx cancer.

PMID- 8153387
TI  - The epididymis and sperm maturation: a perspective.
AB  - In common mammals, sperm leaving the testis are incapable of fertilizing a female
      gamete. Sperm have limited biosynthetic capability and need to minimize demand
      for ATP. Hence, modification of sperm to achieve their maturation requires pre
      programmed cleavage of integral molecules (planned self-modification) and
      remodelling by action of molecules found in the suspending fluids. Most of these
      biocatalysts are secreted by a series of specialized regions in the epididymal
      epithelium, but some are provided in seminal plasma. The role of the epididymis
      in sperm maturation is postulated to be 'setting a series of triggers' each
      capable of initiating cellular changes either at emission or near or in the
      oocyte, and 'setting a safety' for each trigger to prevent premature occurrence
      of the event. The attributes required in a spermatozoon for in vitro
      fertilization and natural mating are different, and their expression is dependent
      on the site of sperm sampling. Some attributes needed for fertility are probably
      like an on-off switch, whereas others probably allow a gradually reduced
      probability of success before going to the off position (analogous to a
      conventional light switch and a dimmer-type light switch). All essential
      attributes of a spermatozoon must be expressed in a 'combined effective amount'
      for that cell to be fertile. Because of mixing, in any segment of the epididymal
      duct the population of sperm is heterogeneous in age and biological status. Thus,
      when assessing sperm maturation it is necessary to establish the proportion of
      sperm that has completed and retained all steps of maturation necessary to
      achieve fertilization of oocytes under the conditions imposed. In a normal
      animal, most sperm leaving the epididymis have a 'combined effective amount' of
      attributes, and the population has a high fertilizing potential.

PMID- 8153388
TI  - Glycolysis and glucose oxidation by the sheep conceptus at different oxygen
      concentrations.
AB  - The effect of changes in oxygen concentration on the catabolic utilization of
      glucose by the sheep conceptus at selected periods between Days 3 and 19 of
      preimplantation development was examined by estimating the production of CO2 and
      lactate from [U-14C]glucose during a 2.5-h culture in vitro in the presence of
      20%, 5% and 1% O2. In general, lowering O2 significantly altered the catabolism
      of glucose with a changing pattern of response depending on the stage at which
      the conceptus was explanted. For embryos at Days 3 and 6 post insemination,
      reduced O2 caused no significant change in oxidative utilization of glucose and a
      small decrease in conversion of the substrate to lactate. By contrast, lowering
      O2 concentration during incubation of the structures of the advanced conceptus
      from Day 13 through to Day 19 of pregnancy significantly restrained oxidative
      utilization of glucose but stimulated its conversion to lactate. The effects of
      these changing levels of O2 on the generation of energy from glucose in the form
      of ATP was estimated. Except for the Day-13 conceptus, reduction in O2
      concentration had little influence on the calculated amount of ATP produced from
      glucose, with glycolysis making up the deficit in energy production when reduced
      O2 inhibits oxidation of the substrate at the later stages of development. At Day
      13, the switch in the metabolism of glucose to glycolysis is not fully effective
      and energy production fell as O2 concentration was reduced. The results indicate
      a major shift towards dependence by the preimplantation sheep conceptus on the
      glycolytic pathway for energy generation from glucose as development progresses.
      This move to glycolysis is increased by low O2 concentration. As a low
      concentration of O2 most probably exists in the lumen of the sheep uterus, the
      results indicate that, in utero, the energy required for the rapid growth of the
      conceptus depends progressively more on glycolysis than oxidative metabolism of
      glucose. The finding that the Day-13 conceptus has not fully adapted to this
      method of ATP generation at low O2 concentrations may make it especially
      vulnerable during development in utero.

PMID- 8153389
TI  - Metabolism of glucose by vesicles derived from sheep trophoblast and embryonic
      discs.
AB  - Samples of trophoblast recovered from the sheep conceptus on Day 13 of pregnancy
      formed spherical vesicles during culture in medium 199. These continued to expand
      and increase in dry weight over the next 6 days in vitro. After 6 days' culture,
      the metabolism of glucose by these vesicles was compared with that of Day-13 and
      Day-19 fresh trophoblastic tissue. The production of CO2 and lactate by vesicles
      was similar, although not identical, to production by Day-13 fresh tissue and did
      not exhibit the marked decrease in glucose catabolism seen in Day-19 trophoblast.
      The tissue from vesicles reacted to reduction in oxygen tension in a manner
      similar to the reaction of fresh tissue, with decreased glucose oxidation and
      increased glycolysis. The activity of the pentose phosphate pathway in vesicles
      was higher, and the activity in Day-19 fresh tissue was much lower, than that in
      Day-13 fresh trophoblast. Incorporation of glucose into the intracellular
      biochemical pools by vesicles was similar to incorporation into Day-13 fresh
      tissue. Limited observations were also made with vesicles derived from embryonic
      disc. Production of CO2 by these vesicles was intermediate between that detected
      in fresh Day-13 and Day-19 embryonic tissue. There were not significant
      differences in lactate production between fresh and cultured samples of embryonic
      tissue. These results show that vesicles formed in vitro remain metabolically
      active but do not mimic the biochemical changes seen in the tissue during
      development in vivo.

PMID- 8153390
TI  - Some effects of genotype and composition of the culture medium on the development
      of mouse zygotes in vitro.
AB  - The effects of EDTA and the presence of glucose and glutamine in CZB medium on
      the development of mouse zygotes of different genotype were investigated.
      Although 30-80% of zygotes (depending on the cross) passed the 2-cell stage in
      EDTA-free medium, the addition of a low concentration of EDTA was necessary in
      these experiments to obtain blastocysts in culture. In reciprocal crosses between
      outbred (Qs), inbred (DBA/2) and hybrid (B10D2F1) stock, there was evidence of a
      strong influence of the maternal genome on zygote development, with those from
      B10D2F1 females performing best irrespective of sire. A paternal influence on
      development was also evident but the most successful sire varied with the
      genotype of female used and reciprocal crosses differed greatly in the ability of
      the resultant zygote to develop in culture. For zygotes recovered from Qs
      females, CZB medium containing glucose and glutamine supported development to the
      blastocyst stage better than did medium devoid of these substrates. Tests with
      embryos from B10D2F1 females indicated that the presence of glucose for the whole
      or for part of the incubation period stimulated blastocyst development. However,
      the addition of glutamine to the medium in these tests had no significant effect
      on the development of blastocysts.

PMID- 8153391
TI  - Metabolism of pyruvate by pre-elongation sheep embryos and effect of pyruvate and
      lactate concentrations during culture in vitro.
AB  - In the first of two experiments, utilization of [1-14C]pyruvate by 8-cell and
      blastocyst-stage embryos derived in vivo was examined during a 3-h incubation in
      HEPES-buffered synthetic oviduct fluid (SOF) medium in the presence or absence of
      other substrates. In the second, a factorial design examined the effect of
      pyruvate (0, 0.33, 1.0 and 3.3 mM) and lactate (3.3, 10 and 33 mM) on development
      of 1- and 2-cell sheep embryos cultured in vitro in a modified SOF medium
      (containing glucose, glutamine and modified Eagle's medium non-essential amino
      acids). Peak utilization of [1-14C]pyruvate was unaffected by the presence or
      absence of other energy substrates. In contrast, rate of utilization was affected
      by the addition of other energy substrates, with half maximal utilization
      occurring at either 0.4 +/- 0.2 mM or 1.2 +/- 0.2 mM for 8-cells and either 0.2
      +/- 0.2 mM or 1.3 +/- 0.3 mM for blastocysts when incubated in the absence or
      presence of other energy substrates respectively. In the second experiment the
      proportion of embryos developing to blastocysts was inhibited by high lactate
      levels (P < 0.001), but was generally not affected by pyruvate concentration.
      However, there was a significant interaction (P < 0.001) between pyruvate and
      lactate when both were present in the medium. At 0.33 mM pyruvate, 3.3 mM lactate
      supported good development (83 +/- 8% blastocysts) whereas 10 mM lactate
      supported less development (50 +/- 11%). However, at the higher levels of
      pyruvate this effect was lost.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153392
TI  - Development of preimplantation guinea-pig embryos in serum-free media.
AB  - This study was undertaken to determine how far preimplantation guinea-pig embryos
      can develop normally in vitro with serum-free media generally used for mouse
      (Whitten's medium, WM) and rabbit (Kane's medium, KM) embryos. Preimplantation
      guinea-pig embryos were recovered from naturally mated females at each day of
      pregnancy between Day 1 and Day 6, and were cultured in vitro with either WM or
      KM at 37 degrees C in 5% CO2 in air. One-cell (Day-1) and 2-cell (early Day 2)
      embryos cultured in WM developed to the 4-cell and morulae stages respectively,
      whereas the corresponding embryos cultured in KM arrested development at the 2
      cell and 8-cell stages respectively. In contrast, 4-cell (late Day 2 and Day 3)
      embryos proceeded to the blastocyst stage in KM, but not in WM. Eight-cell
      embryos (Day 4) and morulae (Day 5) developed to blastocysts in either medium.
      However, hatching of the blastocysts and trophoblast outgrowth on the culture
      dish were supported only by KM even when collected at the blastocyst stage. The
      present study suggests that, in guinea-pig embryos, a distinct change in
      nutritional requirements occurs around the time of the second cell division and
      that, unlike in the mouse, trophoblast outgrowth in the guinea-pig requires no
      supplementation of serum or extracellular matrices.

PMID- 8153393
TI  - Similarity of an oviduct-specific glycoprotein between different species.
AB  - The oviduct provides the best environment in which a zygote can grow and it can
      also support the development of embryos from a different species. However, there
      is no clear explanation of its embryotrophic properties at present. In several
      species, oviduct epithelial cells synthesize and secrete glycosylated proteins
      that become associated with developing embryos. Although these macromolecules may
      have a functional role at the time of fertilization and early embryonic
      development, the nature of such a role remains to be elucidated. The aim of this
      work was to perform a comparative analysis of oviduct-specific glycoproteins in
      search of molecules common to different species since their phylogenetic
      conservation would imply biological significance. In previous studies, sheep
      oviduct-specific proteins were characterized and a monoclonal antibody (AFRC MAC
      264) specific for the sheep oviduct protein 92 (sOP 92) was produced; hence,
      sheep was taken as the reference species. The degree of similarity between sheep
      glycoproteins and those of the cow, goat, pig, rabbit and mouse was determined on
      the basis of: the presence of carbohydrate side-chains, cross-reactivity with
      AFRC MAC 264, correspondence of molecular weight between cross-reacting
      molecules, and similarity of immunohistochemical localization. On this basis,
      proteins similar to sOP 92 were present in cow and goat oviduct. A more limited
      similarity was also observed in pigs. This indicates a certain degree of
      phylogenetic conservation and suggests that these molecules may play an important
      physiological role; however, their function remains to be determined.

PMID- 8153394
TI  - Embryonic development in culture of the marsupials Antechinus stuartii (Macleay)
      and Sminthopsis macroura (Spencer) during preimplantation stages.
AB  - Forty-nine blastocysts from 11 brown antechinus, Antechinus stuartii, and 96
      blastocysts from 17 stripe-faced dunnarts, Sminthopsis macroura, were used to
      develop a culture system for embryos during preimplantation stages. Blastocysts
      of brown antechinus were collected on Days 6-9 for unilaminar stages, Days 16-21
      for bilaminar stages and Days 20 and 21 for trilaminar stages. Blastocysts of
      stripe-faced dunnarts were collected on Day 6 for unilaminar stages, Days 6-8 for
      bilaminar stages and Day 8 for trilaminar stages. Culture media were Dulbecco's
      modified Eagle's medium (DMEM) with 4.5% glucose and Whittingham's T6 medium both
      of which were supplemented with 5, 10, 12.5 and 20% fetal calf serum (FCS).
      Antechinus serum (5%) and bovine serum albumin (0.1%, 0.2%) were also added to
      some media. Human amniotic fluid (HAF) and Monomed media were also tested.
      Blastocysts were cultured at 35 degrees C in 5% CO2 in air. DMEM + 10% FCS and
      HAF supported normal development for the longest periods and over the greatest
      range of stages. Developmental failure of blastocysts in vitro during expansion
      of the unilaminar blastocyst and formation of the bilaminar blastocyst suggests
      that these stages may be dependent on uterine signals. When cultured in DMEM +
      10% FCS, the rate of development of bilaminar and trilaminar blastocysts into
      organogenesis was 4 h slower than in vivo in the stripe-faced dunnart and about 6
      h slower than in vivo in the brown antechinus. Embryos of stripe-faced dunnarts
      were cultured to within 18 h of birth.

PMID- 8153395
TI  - Systemic lupus erythematosus. Antibodies to DNA, DNA-binding proteins, and
      histones.
AB  - Pathogenic autoantibodies to DNA are frequently associated with autoantibodies to
      chromatin-associated proteins such as histones or the Ku (p70/p80) antigens. In
      view of the increasing evidence that autoantibody production is antigen-driven,
      and because DNA is packaged with proteins in the cell, we suggest that anti-DNA
      antibodies may arise in response to DNA-protein complexes rather than naked DNA.
      Recent studies of the specificities of autoantibodies directed against the
      components of nucleosomes and transcriptional complexes are consistent with this
      hypothesis. The possible clinical significance of immune recognition of various
      types of chromatin complexes in autoimmune disease is discussed.

PMID- 8153396
TI  - Pediatric systemic lupus erythematosus and neonatal lupus.
AB  - The clinical manifestations of pediatric systemic lupus erythematosus (SLE) are
      similar to those seen in adults with SLE with increased frequency of the
      following features: hepatosplenomegaly, chorea, nephritis, and avascular
      necrosis. Similarly, pediatric SLE patients are now showing the same improvement
      in survival as adult SLE patients, and it is no longer felt that the course of
      childhood-onset SLE is more severe than that seen in adult-onset SLE. Children of
      mothers with SLE can develop both transient and persistent features of SLE in the
      neonatal period. Transient features include photosensitive discoid rash,
      cytopenia, hepatosplenomegaly, myocarditis, and pericarditis; the permanent
      features include congenital complete heart block, endomyocardial fibroelastosis,
      and other structural cardiac defects.

PMID- 8153397
TI  - Neuropsychiatric lupus.
AB  - Neuropsychiatric disease occurs in up to two thirds of all systemic lupus
      erythematosus patients. At present, there is no accepted classification for the
      myriad of neuropsychiatric manifestations that can be divided into diffuse,
      focal, and seizure presentations. Over the past decade, the pathogenesis of lupus
      cerebritis has become better understood. Consequently, the approach to the
      diagnosis and therapy can often be tailored to the suspected underlying
      etiopathogenesis. Future advancements in therapy will further improve the
      prognosis of patients with neuropsychiatric lupus erythematosus.

PMID- 8153398
TI  - Pleuropulmonary manifestations of systemic lupus erythematosus.
AB  - The pleuropulmonary manifestation of systemic lupus erythematous (SLE) are
      pleuritis, acute lupus pneumonitis, chronic interstitial lung disease with
      fibrosis, alveolar hemorrhage, respiratory muscle and diaphragmatic dysfunction,
      atelectasis, bronchiolitis obliterans, pulmonary vascular disease with pulmonary
      hypertension, and pulmonary embolism. This article reviews these specific
      pleuropulmonary consequences of SLE while focusing on clinical, pathologic, and
      therapeutic considerations.

PMID- 8153399
TI  - Cutaneous manifestations of lupus erythematosus.
AB  - Lupus erythematosus is an autoimmune disease that demonstrates cutaneous,
      systemic, or both cutaneous and systemic manifestations. This article reviews the
      cutaneous manifestations of lupus erythematosus.

PMID- 8153400
TI  - Lupus nephritis. Classification, prognosis, immunopathogenesis, and treatment.
AB  - There is great variation in the characteristics of renal histology, in its
      clinical expression and clinical course, and, most likely, in the pathogenic
      mechanisms of glomerular damage. As the ability to more precisely characterize
      these lesions improves and as we better understand the multiple pathogenic
      mechanisms and modulating factors at play in the disease, treatment advances and
      improved renal survival should follow.

PMID- 8153401
TI  - Antimalarial agents and lupus.
AB  - Antimalarials are under-utilized, disease-modifying agents that are useful in the
      management of lupus erythematosus. Antimalarials can promote a remission in non
      organ-threatening lupus and decrease its risk of dissemination. They are
      especially useful for cutaneous and inflammatory joint disease and have modest
      actions in improving serositis, fatigue, and cognitive dysfunction. As agents
      that do not depress the bone marrow or promote opportunistic infections,
      antimalarials have potential applications in combination with other antilupus
      medications and with each other.

PMID- 8153402
TI  - Immunosuppressive drug therapy of systemic lupus erythematosus.
AB  - This article reviews the biologic effects of cyclophosphamide and azathioprine
      relevant to the treatment of systemic lupus erythematosus (SLE). Other agents
      used less commonly for SLE, such as methotrexate, chlorambucil, and cyclosporin
      A, receive more limited attention. Clinical studies of efficacy and toxicity of
      these agents in their treatment of SLE are then described in detail.

PMID- 8153403
TI  - Systemic lupus erythematosus. Antibodies to ribonuclear proteins.
AB  - This review has emphasized that utility of measuring the autoimmune responses to
      several RNP antigens in the diagnosis of SLE, as well as their use in delineating
      clinical subsets. The future of this area lies in the definition of the
      pathogenetic mechanisms that link these autoimmune responses to clinical
      expression of disease.

PMID- 8153404
TI  - Antiphospholipid antibody syndrome.
AB  - The antiphospholipid syndrome is now well recognized and is separable from SLE,
      but better quantitation of both the clinical elements and the serologic
      definitions is still needed. It is likely for autoimmune but not for infection
      induced aPL that the antigen is not phospholipid itself but a complex formed by
      phospholipid and beta 2 glycoprotein I. There are few treatment trials yet
      published. Those that are available suggest that antiplatelet therapy or
      anticoagulant therapy are more valuable than is immunosuppression.

PMID- 8153406
TI  - [Current status of thyroid tumors].

PMID- 8153407
TI  - [Progressive multifocal leukoencephalopathy in acquired immunodeficiency
      syndrome].
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic
      infection in HIV-infected persons. We present the characteristics of seven cases
      of PML, which represent 3.1% of our patients with AIDS. In six cases, was the
      "marker" disease for AIDS. The most common clinical manifestation was a slowly
      evolving focal neurological syndrome (average time of pre-hospitalization
      symptoms was 64 days). The number of T4 lymphocytes at the moment of diagnosis
      varied between 14 and 121 cel/mm3 (median: 51). Computerized tomography (CT) and
      cranial nuclear magnetic resonance (NMR) showed images of single (4 cases) or
      multiple white substance involvement without contrast uptake or mass-effect. The
      definitive diagnosis was made by cerebral biopsy. Four died within 20 to 90 days
      of diagnosis. Three of the five who received antiretrovirals survived with
      apparent stabilization of the process at 2, 13, and 23 months of diagnosis. PML
      can be an initial diagnostic disease for AIDS. Its symptoms and the CT/NMR should
      arouse suspicion. However, given that clinicoradiological data are often
      insufficient, it is advisable to conduct cerebral biopsies. Antiretrovirals may
      have a favorable effect on diseases course.

PMID- 8153405
TI  - Systemic lupus erythematosus and pregnancy.
AB  - Although most women with systemic lupus erythematosus can achieve a successful
      pregnancy, fetal (fetal loss, preterm birth) and maternal (lupus flares,
      worsening renal function) morbidity remain major problems. Predictors of fetal
      loss and preterm birth have been identified and are reviewed. Modern management
      of lupus pregnancy includes identification of high-risk pregnancies with
      appropriate monitoring and treatment (when indicated) for anti-Ro and
      antiphospholipid antibodies, frequent assessment of and control of maternal lupus
      activity, adjustment of medications to avoid those associated with fetal
      teratogenicity, and the appropriate use of fetal assessment tests to guide
      intervention for the fetus at risk of intrauterine death.

PMID- 8153408
TI  - [Chronic gastroenteritis caused by Plesiomonas shigelloides in adult patients.
      Report of 3 cases].
AB  - We report the clinical characteristics of three adult patients with a chronic
      gastroenteritis (more than 10 days duration) due to Plesiomonas shigelloides. The
      three patients presented previously an underlying disease; a chronic liver
      disease (alcoholic and viral) and a cancer disease. Although the immunosuppressed
      condition of the patients, the diarrhea was moderate with 6-12 movements/day; the
      feces were liquid with mucose and blood. No one patient presented fever but all
      of them had important abdominal pain. Two patients were treated with
      cotrimoxazole and ciprofloxacin because of their underlying disease. We review
      the clinical characteristics of chronic diarrhea caused by P. shigelloides in
      adult patients, and the possibility that this microorganism would be considered a
      true enteropathogen.

PMID- 8153409
TI  - [Flocculation of NPH insulin].
AB  - In the past decade, human insulins have been substituting animal insulins,
      offering the advantage of its lesser antigenic capacity. One of the most
      clinically important problems with human NPH insulins is its tendency to
      flocculate. We present four diabetic patients who, after using flocculated human
      NPH insulin, encountered a deterioration in the metabolic control of their
      diabetes, and in two of them, there were bouts of diabetic Ketoacidosis "without
      any other apparent causal factors". Among those causes favoring flocculation are
      movement during transport, high temperatures, and probably leaving the vial open
      for an excessively long period of time, as with the extraction of multiple doses.
      Physicians, educators, diabetics, and their relatives should be informed of this
      phenomenon. Diabetics, especially those who carry insulin with them, should
      carefully inspect their vials before each injection to detect signs of
      flocculation.

PMID- 8153410
TI  - [Cholesterol embolism].
AB  - Two patients with advanced atherosclerotic vascular disease developed multiple
      cholesterol emboli. In both patients the clinical presentation included livedo
      reticularis of the lower part of the body and purple toes with small areas of
      distal necrosis and ulceration. The predisposing factors are operative vascular
      procedures and the use of anticoagulants respectively. Biopsy of skin lesions
      revealed characteristic cholesterol clefts within atheromatous debris filling
      small, deep arterial lumen. Multiple cholesterol emboli should be suspected in
      presence of cutaneous lesions and confirmed histologically in the appropriate
      clinical setting.

PMID- 8153411
TI  - [Diabetic woman with arterial hypertension, hypercholesterolemia, and trigeminal
      neuralgia. Transitional type meningioma and fibroblastic predominance].

PMID- 8153412
TI  - [Young male with changes in thorax and pancreatic area. Mucoviscidosis or cystic
      fibrosis].

PMID- 8153413
TI  - [Anatomoclinical and diagnostic characteristics of thyroid carcinoma. Study of
      126 cases].
AB  - A retrospective review was conducted among 126 patients treated for thyroidal
      carcinoma--86 papillary, 31 follicular, 4 anaplastic, 1 lymphoma, and 4 non
      familiar medullary--in our area between 1979 and 1992. Diagnostic and clinical
      findings obtained were evaluated along with those from physical examinations,
      imaging techniques (i.e., echography and gamma spectrometry), and histological
      study (i.e., fine needle puncture-aspiration and intra-operatory biopsy). The
      majority (88 cases) presented a hard node or one of elastic consistency, while in
      34 cases, there was a diffuse or nodular increase. Only four patients manifested
      a normal thyroid in the physical examination. A 2.4% had a normal gammagraphy,
      70% presented a cold node, 1.6% an alient node, and there was evidence of
      heterogeneous uptake in 23.7%. In the echography study, 63.3% were noted as being
      solid nodes, 11.4% as cysts, and 24% as mixed. The sensitivity of the fine needle
      puncture-aspiration was 76.4% and 66.6% for intraoperative biopsy.

PMID- 8153414
TI  - [Clinical approach to the diagnosis and treatment of deficiency anemia].

PMID- 8153415
TI  - [Cushing's syndrome].

PMID- 8153416
TI  - [Physiopathology and treatment of acute gouty arthritis].
AB  - Severe gouty arthritis is a clinical expression of a very intense inflammatory
      process. The initial pathogenic event which sets off the chain process is the
      intraarticular deposit of monosodium urate crystals. However, urate crystals do
      not always promote an inflammatory process (e.g., dormant tophus), and only a
      minority of patients with hyperuricemia develop gout. The therapeutic bases for
      gout should be based on the knowledge surrounding the physiopathology of the
      inflammatory process. In this study, we present the physiopathology of severe
      gouty arthritis in order to improve understanding of its treatment.

PMID- 8153417
TI  - [Nephrotoxicity caused by diclofenac].

PMID- 8153418
TI  - [Aortic dissection and fever of unknown origin].

PMID- 8153419
TI  - [Permanent pacemaker in Reiter's syndrome].

PMID- 8153420
TI  - [Miliary tuberculosis and cirrhosis].

PMID- 8153421
TI  - [Metachronic neoplasms in the lung].

PMID- 8153422
TI  - [Rheumatoid arthritis and hepatic nodular regenerative hyperplasia].

PMID- 8153423
TI  - [Malignant tumors of the Vater's ampulla. Presentation of 28 cases and review of
      the literature].
AB  - We present a study of 28 patients, treated for adenocarcinoma of Vater's ampulla.
      We emphasize the distinct behavior of each one of the peri-ampullar tumors, those
      which affect Vater's ampulla yielding the best prognosis. We gathered data
      regarding gender, age, clinical manifestations, and analytical data. The
      confirmatory diagnosis gives us 100% of CPRE cases. All of the patients were
      submitted to surgical treatment with anatomic pathological confirmation of the
      diagnosis, be it pre or postoperative. We practiced curative surgery in 57.2% of
      the cases and palliative in 42.8% of the cases. We observed postoperative
      complications in 17.8% of the patients and peroperative mortality in 3.5%. Actual
      survival of the series of patients for whom exeretic surgery was performed is
      significantly superior to that of the other patients.

PMID- 8153424
TI  - [1993 and 1994 Meetings of the Societies of Pneumology of the French Language.
      Abstracts].

PMID- 8153425
TI  - Epidemiology of cancer of the oral cavity and oropharynx.

PMID- 8153426
TI  - Curietherapy versus external irradiation combined with curietherapy in stage II
      squamous cell carcinomas of mobile tongue and floor of mouth.

PMID- 8153427
TI  - Present status of EORTC trials of hyperfractionated and accelerated radiotherapy
      on head and neck carcinoma.

PMID- 8153428
TI  - Second primary tumors in oral and oropharyngeal cancer.

PMID- 8153429
TI  - Induction chemotherapy for organ preservation in advanced squamous cell carcinoma
      of the oral cavity and oropharynx.

PMID- 8153430
TI  - Carcinomas of the oropharynx treated with hyperfractionated radiation therapy on
      Radiation Therapy Oncology Group Protocol 8313.

PMID- 8153432
TI  - Simultaneous preoperative radiochemotherapy with cisplatin in advanced oral
      cavity carcinomas: acute response and follow-up.

PMID- 8153431
TI  - Preoperative radiochemotherapy and radical surgery of advanced head and neck
      cancers--results of a prospective, multicenter DOSAK study.

PMID- 8153433
TI  - Extended surgery for advanced maxillary sinus carcinoma.

PMID- 8153434
TI  - Results from DOSAK observational studies.

PMID- 8153435
TI  - Current trends in therapeutic research.

PMID- 8153436
TI  - The radiobiology, treatment, and prevention of osteoradionecrosis of the
      mandible.

PMID- 8153437
TI  - Epiprosthetic rehabilitation: patient's acceptance of a facial epithesis
      following tumor surgery.

PMID- 8153438
TI  - Value of follow-up in patients treated for squamous cell carcinomas of the oral
      cavity and oropharynx.

PMID- 8153439
TI  - Resection of tumors in tongue, floor of the mouth, and mandible: possibilities of
      primary reconstruction.

PMID- 8153440
TI  - Surgery of oropharyngeal cancer.

PMID- 8153441
TI  - Surgical management of cervical lymph nodes in patients with oral and
      oropharyngeal cancer.

PMID- 8153442
TI  - Radical neck dissection versus conservative neck dissection for squamous cell
      carcinoma of the oral cavity.

PMID- 8153443
TI  - Treatment of oropharynx carcinomas: experience at the Institute Gustave-Roussy.

PMID- 8153444
TI  - Concomitant boost-accelerated, superfractionated irradiation for the treatment of
      advanced carcinomas of the oral cavity and oropharynx.

PMID- 8153445
TI  - Regional lymph node irradiation.

PMID- 8153446
TI  - Radiotherapy with different fractionations and simultaneous cisplatin or
      carboplatin in the treatment of advanced head and neck carcinomas: clinical
      results and radiobiological investigations.

PMID- 8153447
TI  - Clinical relevance of precancerous lesions of oral mucosa.

PMID- 8153448
TI  - Mechanisms and meaning of cellular oxygen sensing in the organism.
AB  - Oxygen sensors in the body induce various cell activities to avoid any mismatch
      between oxygen demand and oxygen supply and to maintain an optimal level of
      oxygen partial pressure (PO2) in various organs. Oxygen sensing seems to be a
      well conserved process among procaryontic and eucaryontic cells. The molecular
      mechanism of oxygen sensing is unknown, but it has been suggested that a
      hemeprotein is involved that does not participate in the mitochondrial energy
      production. As examplified on the carotid body and on erythropoietin producing
      HepG2 cells, a cytochrome b was described for the NAD(P)H oxidase of neutrophiles
      might be an attractive candidate for this hemeprotein. It is hypothesised that
      hydrogen peroxide (H2O2) produced by this cytochrome b in direct correlation with
      cellular PO2, serves as a second messenger to regulate potassium channels or gene
      expression. One might forsee, that this new concept of oxygen sensing could have
      an impact on all processes in physiology and pathophysiology which are dealing
      with reactive oxygen intermediates.

PMID- 8153449
TI  - Does peak inspiratory flow contribute to setting VO2max? A test of symmorphosis.
AB  - Symmorphosis predicts that animal design is optimized in such a way that
      structure 'statisfies but does not exceed' functional requirements. To provide
      one test of this hypothesis, we examined peak inspiratory flow and its relation
      to maximum oxygen uptake in humans. We measured maximal forced (peak) inspiratory
      flow (VImax) and maximum oxygen uptake (VO2max) via cycle ergometry in well
      trained (VO2max > 65 ml O2.kg-1.min-1) and untrained (VO2max < 45 ml O2.kg-1.min
      1) male subjects. Tests of VImax and peak oxygen uptake (VO2peak) were made while
      the subjects were breathing through inspiratory orifices differing in area. VImax
      varied as an identical function of orifice diameter in both groups of subjects.
      However, VO2peak was more sensitive to decreasing orifice diameter in trained
      endurance athletes than it was in untrained individuals. The diameter of the
      largest orifice that caused a reduction in oxygen uptake was over two times
      larger for trained than for untrained subjects, corresponding to about a four
      fold difference in resistance at any flow rate. These results suggest that the
      structures setting VImax (airway resistance and inspiratory muscle strength) are
      not matched to oxygen demand (VO2max) in humans. While these structures seem to
      be 'over-built' and hence do not likely contribute to setting the limits to
      aerobic performance in most humans, they may be among the primary limiting
      factors in the most elite endurance athletes.

PMID- 8153450
TI  - Calcium deficient diet, acetazolamide and gas exchange characteristics of avian
      eggshells.
AB  - The effects of calcium deficient diet and acetazolamide on the gas exchange
      characteristics of avian eggshells were independently investigated in two groups
      of unmated hens (Gallus domesticus). In one group, eggs were collected during
      both a normal diet (3.00% Ca) and a calcium deficient diet (0.34% Ca). In another
      group, eggs were collected both before and after acetazolamide administration
      (200 mg/kg) per os. Eggshell water vapor conductance (GH2O) increased 30% during
      the calcium deficient diet and was accompanied by a 21% decrease in eggshell
      thickness (L). Eggshell GH2O increased 200% one day after acetazolamide
      administration and was not only accompanied by a 36% decrease in L, but also by
      an 89% increase in total functional pore area (Ap). We conclude that a calcium
      deficient diet increases GH2O by eggshell thinning with little effect on Ap. On
      the other hand, acetazolamide profoundly increases GH2O, not only by eggshell
      thinning but also by a remarkable increase in Ap.

PMID- 8153451
TI  - Respiratory mechanics of the horse during the first year of life.
AB  - This study investigated the developmental changes in the mechanical properties of
      the respiratory system in growing horses. Pulmonary mechanics and lung volumes
      were serially measured in anesthetized foals during the first year of life. Quasi
      static pressure-volume curves were generated, and functional residual capacity
      (FRC) was measured using a closed nitrogen equilibration technique. At birth,
      chest wall compliance normalized to body weight was substantially less than that
      reported in other less precocious newborn species, while lung compliance
      normalized to body weight was similar to values reported for other species.
      Characteristics of the transition from the neonatal to adult respiratory system
      in the foal included a decrease in the ratios of chest wall to lung compliance
      (Cw/CL) and the unstressed volume of the chest wall to TLC, and a constant
      FRC/TLC throughout most of the study period. The somatic growth of the foal and
      its respiratory system were uneven processes, with increases in lung volume
      lagging increases in overall body size.

PMID- 8153452
TI  - Impairment of surfactant activity and ventilation by proteins in lung edema
      fluid.
AB  - We investigated the effects of lung edema protein on ventilatory mechanics with
      special reference to surfactant activity. The edema fluid was obtained from
      hyperoxia-exposed adult rabbits. In immature newborn rabbits that could not be
      artificially ventilated at an insufflation pressure of 25 cm H2O, mean tidal
      volumes of > 27 ml/kg were obtained by supplementation with a natural surfactant
      (S-alone) or natural surfactant mixed with lung edema fluid (EF), the edema
      protein-to-surfactant ratio of which was < or = 5.6. A mixture with a ratio of
      11.2 (11.2-EF/S), however, decreased the volume to 10.9 ml/kg (P < 0.05 vs S
      alone). Surfactant mixed with isolated albumin at a concentration equal to that
      in 11.2-EF/S decreased the tidal volume to 8.6 ml/kg (NS vs 11.2-EF/S), and with
      isolated fibrinogen lowered it to 18.1 mg/kg (P < 0.05 vs S-alone). We conclude
      that lung edema fluid impairs ventilation through surfactant inactivation when
      the protein-to-surfactant ratio increases, and that albumin and fibrinogen are
      the main causes of this impairment.

PMID- 8153453
TI  - The Fowler breathholding study revisited: continuous rating of respiratory
      sensation.
AB  - The respiratory distress of breathholding has been shown to be relieved by
      breathing, even without correction of worsening blood gases (Fowler, 1954). We
      repeated the study by having untrained normal subjects perform maximal
      breathholds which were followed by the rebreathing of a gas mixture containing
      7.5% CO2 and 8.2% O2, and then by second breathholds. In addition, we had the
      subjects continuously rate their respiratory distress using a visual analog scale
      (VAS). The ratings were easy to perform and were highly reproducible on repeated
      trials in a given subject. Subjects experienced increasing distress during the
      breathhold, rapid and substantial relief upon rebreathing, and then were capable
      of performing second breathholds, all consistent with Fowler's results. The
      findings are consistent with animal studies in which a neural mechanism
      associated with stimulation of pulmonary stretch receptors inhibits the firing of
      midbrain neurons which may be involved in transmission to the cortex of sensory
      information about breathing.

PMID- 8153454
TI  - Chemoreceptors and control of episodic breathing in the bullfrog (Rana
      catesbeiana).
AB  - To test the hypothesis that the episodic breathing pattern of bullfrogs is
      necessarily caused by fluctuations of PaO2 and PaCO2/pH, the natural oscillations
      of blood gases associated with periods of ventilation and apnea were
      experimentally prevented by unidirectional ventilation (UDV) of lungs. UDV with
      air or a 50% O2 in N2 gas mixture eliminated breathing episodes; only sporadic
      single breaths were ever observed under these conditions. UDV with hypoxic or
      hypercarbic gas mixtures, however, produced episodic breathing despite the fact
      that UDV virtually eliminated fluctuations in pHa, PaCO2 and PaO2. Furthermore,
      the breathing patterns of animals with the same mean levels of blood gases and
      acid-base status, with (UDV) and without (non-UDV) phasic chemoreceptor input
      were identical. These data indicate that phasic chemoreceptor input plays little
      or no role in the control of the normal breathing pattern although some tonic
      level of chemoreceptor input is required for ventilation to occur. Animals on UDV
      were more sensitive to hypercarbic than hypoxic gases and hypoxemia and
      hypercapnia affected breathing pattern differently. This indicates that tonic
      chemoreceptor input also affects the length of the periods of apnea and
      ventilation but this must be through some mechanism other than an "on" or "off"
      threshold.

PMID- 8153455
TI  - [Ultrafast computed tomography and nuclear magnetic resonance, the foremost
      methods in cardiovascular examination].

PMID- 8153456
TI  - [Pneumothorax: its etiology, clinical aspects and treatment].

PMID- 8153457
TI  - [Mitral valve prolapse. II. The clinical profile: the prolapse syndrome and
      anatomical prolapse].

PMID- 8153458
TI  - [Suicidal behavior: the medicolegal epistemology (I)].

PMID- 8153459
TI  - [Bioethics in Iasi].

PMID- 8153460
TI  - [Oral villous leukoplakia, a new clinico-pathological entity].

PMID- 8153461
TI  - [Myocardial infarct in children. The anatomicoclinical aspects].
AB  - Nine cases of myocardial infarction in the newborns (8 cases aged between 7 days
      and 6 months) and infants (1 case aged 12 years and 6 months) were followed up
      for 15 years. The etiology was different: mediocalcosis of the coronaries,
      congenital abnormalities of the heart marked hypertrophy of left ventricular
      myocardium (endocardial fibroelastosis or nonobstructive hypertrophic
      cardiomyopathy) severe hypoxia (severe acute bronchopneumopathies), and AAR,
      cardioarticular form, with multiple attacks in the infant. The ECG aspects were
      not specific in most children and clinically the prevailing finding was severe
      decompensated cardiac failure. The main etiologies and the inducing mechanisms of
      myocardial infarction in children are presented.

PMID- 8153462
TI  - [The cardiac manifestations in hyperthyroidism. The surgical implications].
AB  - In a statistics including 954 patients with hyperthyroidism [correction of
      Huprotoncoses] treated between 1966-1989, the authors found 522 cases (54) with
      various associated cardiac disorders. Of these cases, 199 presented rhythm
      disturbances: extrasystolic arrhythmia, auricular fibrillation and flutter to
      which 34 postoperative arrhythmias are added. Cardiac insufficiency present in 46
      cases was the main complication and end point of the various myocardial
      conditions. Ischemic cardiopathy (181 cases), arterial hypertension (98 cases)
      and rheumatic valvulopathies (9 cases), either isolated or dominating the
      clinical picture, complete the nosological spectrum of these disturbances. The
      frequency of associated conditions and the absence of some specific morphologic
      lesions suggest that thyrotoxicosis is rather an aggravating factor although in
      many cases the presence of a previous cardiac disease is excluded. The two
      objectives in the management of thyrocardiac diseases are the amelioration of
      cardiac condition and an endocrine balance. In the conditions of a careful
      selection and preoperative preparation, surgery gave good results consisting, in
      this series, in over 70% cures and ameliorations.

PMID- 8153463
TI  - [Mechanical anastomoses in esophagogastric surgery for malignant tumors].
AB  - The authors present their experience in employing for the first time the
      mechanical circular suture with I.L.S. stapler in the surgery of 10 malignant
      esophagogastric tumors sited in C (4 cases) and M areas (6 cases). The disease
      was in stage II in 2 patients and in stage III in the remainder of 4. Three upper
      polar esophagogastrectomies (Akiyama technique) and 7 total gastrectomies were
      performed in old patients (mean age 63 years) at high surgical risk. Neither
      death nor fistulas were recorded. The average hospital stay was 14 days. A series
      of 17 patients (mean age 59 years), at medium surgical risk, with total
      gastrectomy for gastric carcinoma and classical suture served as controls. Five
      fistulas, two deaths and a two times longer hospital stay were recorded. Although
      the high cost of staplers prohibits the routine use of this technique, the
      authors demonstrate the great advantages resulting from mechanical suture in
      esophagogastric surgery.

PMID- 8153464
TI  - [Surgical treatment in osteochondritis of the femur head in children].
AB  - The goal of surgery in the femoral head osteochondritis of children is, in the
      cases progressing towards extrusion, to ensure a good coverage of femoral head.
      Under the age of 5-6 years, the evolution being more commonly benign, the
      surgical containment is rarely indicated. In the child over 7 years, the
      extrusion of femoral head being common, a surgical intervention for correcting it
      is necessary. This paper is based on a statistics on 36 children operated upon at
      the Clinic of Pediatric Surgery and Orthopedics of Iasi between 1980 and 1990.
      Eighteen femoral osteotomies, 10 Chiari pelvic osteotomies and 8 triple pelvic
      osteotomies were performed. It is assumed that femoral osteotomy is rarely
      indicated and Chiari osteotomy is required for hip salvage when other techniques
      cannot be used. The triple pelvic osteotomy, when indicated, has to be used more
      frequently, leaving aside the reticences towards this method.

PMID- 8153465
TI  - [Distinguished pharmacists among the members of the Society of Physicians and
      Naturalists].

PMID- 8153466
TI  - [The frontal bonding of a microprosthesis with respect to arch physiognomy].
AB  - A series of 4124 patients who presented at the Gnathoprosthetic Clinic of Iasi
      with dental coronary lesions were investigated. The dental lesions situated at
      the level of frontal arches, the possibilities of aggregating the microprostheses
      at this level and the clinical-technical procedure of realizing them were
      studied. By the joint efforts of the entire dental team, artificial substitutes
      completing the lack of dental substance were obtained and the physiognomic
      function, cosmetic harmony and facial esthetics were fully restored.

PMID- 8153467
TI  - [The medical world seen from the following century].

PMID- 8153468
TI  - Detection of beta-lactamase production and enzyme profiles in Enterobacteriaceae
      isolated in Moldova.
AB  - In our study, out of 449 Enterobacteriaceae strains isolated between 1985 and
      1990, 16 strains (3 Proteus, 6 nontyphoidal Salmonella, 7 Escherichia coli) were
      resistant both to Ampicillin- Sulbactam and Amoxycillin-Clavulanic acid
      associations. The activity profiles of the beta-lactamases produced by these
      resistant strains are described. Sarcina lutea ATCC 9341 was used as test strain.
      The effect of the enzymatic filtrate against beta-lactam antibiotics: Ampicillin,
      Cloxacillin, Cefadroxil, Cefuroxime, Cefotaxime, Ceftriaxone, was followed up.
      The enzyme types were established according to the ability of inactivating the
      tested antibiotics. Penicillins and cephalosporins were inactivated by these
      enzymes, except for Carbenicillin and Oxacillin. These beta-lactamases were
      resistant to Sulbactam and Clavulanic acid. In the studied Salmonella strains
      they are plasmidic codified, demonstrating that they belong to a new beta
      lactamase class.

PMID- 8153469
TI  - [The antibacterial action of new hydrazide derivatives].
AB  - New derivatives of 4-aminobenzoic and 4-chlorine-2-hydroxybenzoic acids
      hydrazides were synthesized by the condensation reaction of these hydrazides with
      aldehydes and ketones, derivatives containing in their molecule azometine and
      hydrazone groups. The obtained products are potentially bioactive. The study of
      their "in vitro" biological activity was performed on some pathogenic germs, both
      gram-positive and gram-negative. The results show that the tested substances are
      more active towards the gram-positive germs.

PMID- 8153470
TI  - [The epidemiology of nontransmissible diseases in update].

PMID- 8153471
TI  - [The mechanisms of action of etophylline-clofibrate in hyperlipidemia].

PMID- 8153472
TI  - [The pharmacotechnical assessment of the types of sodium carboxymethylcellulose
      of Romanian origin (its synthetic appearance)].
AB  - Three indigenous varieties of sodium carboxymethylcellulose, types 1,000, 6,000
      and 10,000, with properties comparable to those of similar imported products were
      investigated in view of determining their qualities of excipients for some
      pharmaceutical products. Thus, they were used for obtaining a potassium chloride
      containing syrup, buvable ampoules with diethylaminoethanol N-acetylglutamate.
      Ointment bases and tablets with favorable qualities were also obtained.

PMID- 8153473
TI  - [The sleep apnea syndrome (SAS)].

PMID- 8153474
TI  - [The effect of the ascorbic acid-Cu (II) couple on enzyme activity].
AB  - Ascorbic acid (AA), Cu (II) and their association affect in different ways the
      activity of G6P-ase and G6PDH from the rat hepatic cytoplasm enriched in
      microsomes. G6P-ase is inhibited at a wide range of concentrations: 200-2 mM AA
      and 1-0.1 mM Cu (II). The association AA-Cu in the above mentioned
      concentrations, proved to be a stronger inhibitor than AA or Cu (II) introduced
      separately in the incubation medium. The activity of G6PDH is stimulated by AA-Cu
      (II) association and inhibited by AA in the dialyzed and nondialyzed cytoplasm.
      Cu (II) inhibits the activity of G6PDH in the nondialyzed cytoplasm and
      stimulates it following dialysis. The compounds with recognized antiradical
      action prove to be inefficient in restoring the activity of G6PDH affected by the
      AA-Cu (II) association.

PMID- 8153475
TI  - Efficacy of multidisciplinary epidemiological screening in the primary prevention
      of essential arterial hypertension.
AB  - An epidemiological screening of 8011 industrial workers and 7090 pupils made
      possible the active detection of some risk factors carriers and of those
      individuals with borderline essential arterial hypertension (BEAHT) and essential
      arterial hypertension disease (EAHTD). It was noticed that the association of 2-4
      risk factors is more common in the subjects with BEAHT or EAHTD, fact indicating
      their increased aggressivity in the various types of associations present in the
      same carrier. In the worker series a prevalence of 16.2%-18.0% for BEAHT and 6.3%
      7.1% for EAHTD as compared to 4.3%-6.0% and 4.9%-5.3%, respectively, in the pupil
      series were recorded. The epidemiological screening had a strong educational
      effect, reflected in an increased cooperation of the screened population, and
      revealed the fact that the risk factor carrier state and the increased arterial
      pressure levels were ignored, at long term, by 50-90% of the investigated
      subjects.

PMID- 8153476
TI  - [Seroepidemiological data on the circulation of influenza virus in Moldova in
      1991-1992].
AB  - OBJECTIVES: 1. To establish the predominant circulating antigenic subtypes of
      influenza viruses in the epidemic season (19911992). 2. To evaluate the
      efficiency of seroepidemiological method in determining the circulating antigenic
      subtypes and its practical consequences. METHODS: Our study consist of 1082
      patients with acute respiratory disease or their contacts. Antigens prepared at
      "Cantacuzino Institute", C.D.C. Atlanta and from viral strains isolated in our
      laboratory were used. Hemagglutination-inhibiting Test was preceded by the
      elimination of the unspecific inhibitors with IO4K M/90. Significant titers were
      considered those > 1/10. RESULTS: Were assessed by determining the number of
      antibody carriers, their ratio and geometrical mean of the reciprocal value of
      H.I. antibody titers. CONCLUSIONS: 1. In the winter of 1991 and 1992 A/H3N2
      infections and in the spring 1991 and 1992 A/H1N1 virus prevailed, while B virus
      circulated by the end of spring 1992 epidemic season. 2. The decrease in 1992 of
      A/Iasi/1/69 (H3N2) activity at the same time with high titers against A/Iasi/1/76
      (H3N2) and A/Iasi/1/80 (H3N2) suggests a marked antigenic drift occurring in this
      interval 3. Serological method for determining the presence of hemagglutination
      inhibiting antibodies seemed enough and compulsory for detecting the etiological
      agent of acute respiratory disease, and an epidemic outbreak. 4. The circulation
      of three distinct antigenic subtypes determines the options for composition of
      anti-influenza vaccine.

PMID- 8153477
TI  - [Illumination in schools, a health problem for the developing body].
AB  - The relationship between lightening degree in schools and vision problems was
      investigated in a series of 500 pupils (aged between 11 and 14 years) from both
      rural and urban areas, schooled in 21 different classrooms. The tests revealed
      that natural lightening is observing the health standards in a percentage of 100%
      in the urban classrooms and is deficient with 16.64% in the rural ones.
      Artificial lightening is inappropriate in all investigated classrooms (both rural
      and urban). Vision, estimated by visual acuity test, proved to be more affected
      in the rural areas (14% of the children) where lightening conditions are more
      deficient, than in the urban pupils (12.8%). It was also noticed that the active
      detection index of vision disturbances is lower in the rural as compared to urban
      pupils (5.7% and 28.12%, respectively). School lightening should be a priority in
      the public health programs.

PMID- 8153478
TI  - [The possibilities for increasing iodine stability in the salt from Tg. Ocna
      saline].
AB  - Given the important iodine losses in the iodate salt from Tg. Ocna saltworks, we
      attempted in our laboratory at iodinating this salt with potassium iodate and
      iodure in concentrations of 25% mg/kg salt and 35 mg/kg salt using sodium
      carbonate 1 g/kg salt as stabilizing agent. The results of this study showed that
      our method was efficient, the iodine losses being minimal at concentrations of 35
      mg/kg salt.

PMID- 8153479
TI  - [The presence of detergents in surface water sources and their health and
      ecological implications].
AB  - The presence of anionic detergents in some surface waters (the Danube River in
      its inferior sector, the Prut River and its affluents, and the lakes on the
      Bistrita River) which are sources of drinking water for some towns was
      investigated. The presence of the anionic detergents is due to the discharge of
      industrial and household waste waters. Although the anionic detergents levels are
      low they raise health problems as these substances may favor the digestive
      absorption of some noxious or carcinogenic substances concomitantly present in
      the water source.

PMID- 8153480
TI  - [The characteristics of medical health care at the level of the rural medical
      dispensary in Iasi County].
AB  - Attributes of health care in a rural health center from Iasi (57.20%) and
      preventive actions (42.80%), with an average annual medical care of 1.15
      days/person. Given the increased number of elderly in the respective area, the
      degenerative diseases (cardiovascular, rheumatic, chronic respiratory) are
      prevalent. Prevention mainly consists of vaccinations (26%).

PMID- 8153481
TI  - Social obligations in medical research: medical aspects.

PMID- 8153482
TI  - [Pericardial hydatidosis. A clinical case].
AB  - We present a case of intrapericardial hydatidosis in a 56 year old man. The
      clinical and paraclinical investigations revealed a tumoral structure which is
      localised in the right costo-phrenic sinus without stating precisely the etiology
      and localisation of the tumoral structure. The thoracotomy points out the
      multilocularis intrapericardial hydatidosis, that was surgically solved. The case
      is very important by the rare occurrence, the diagnosis difficulties and surgical
      treatment.

PMID- 8153483
TI  - [A population study of certain traits of multifactor determination in the
      expertise of family relationship].

PMID- 8153484
TI  - [The medical world of the year 1892].

PMID- 8153485
TI  - [Trichinelliasis, a parasitosis of renewed current interest].

PMID- 8153486
TI  - [The somatogram--a diagnostic and prognostic element in extensive and total
      anodontia].

PMID- 8153487
TI  - [The importance of screening for visual acuity].

PMID- 8153488
TI  - [Asklepios of Epidauros, the quintessence of Hellenic medical thought].

PMID- 8153489
TI  - [The university model and adaptation. I. Student opinion].

PMID- 8153490
TI  - [Dr. Andrei Trosc--a personality in Iasi medicine of the interwar years].

PMID- 8153491
TI  - [The concerns and traditions of the Iasi school of medicine reflected in the
      pages of the Revista Medico-Chirurgicala].

PMID- 8153492
TI  - [Prof. Gh. Gh. Popovici--a distinguished servant of the Iasi school of medicine].

PMID- 8153493
TI  - Women recovering from coronary artery bypass surgery.
AB  - Coronary heart disease is the leading cause of death among American women over
      50, and women are undergoing surgical revascularization procedures in ever
      increasing numbers. There are, however, little research-based data upon which to
      guide the nursing care of these patients. This study explored the nature of the
      recovery process for women following coronary bypass surgery in order to extend
      our understanding of the posthospitalization phase of the recovery trajectory.
      Ten patients participated in semi-structured interviews that were analyzed using
      thematic analysis. Data reveal significant problems with caregiver recognition
      and access to care. Barriers to care may also exist due to women's traditional
      subordinate role in American society and their use of gender specific interactive
      skills. Recovery for women was found to differ significantly from that: of men
      due to the later developmental stage when women are more likely to experience
      cardiac illness.

PMID- 8153494
TI  - Operationalizing the Corbin & Strauss Trajectory Model for elderly clients with
      chronic illness.
AB  - A research team of six nursing faculty at Thomas Jefferson University College of
      Allied Health Sciences collaborated to develop a research proposal to provide
      nursing care to a selected population of chronically ill elderly persons. The
      Corbin and Strauss Nursing Model for Chronic Illness Management (1991) was
      selected as the organizing framework to guide research and care delivery. While
      conceptual models offer direction for nursing practice, specific guidelines for
      providing care can only be identified when major concepts of the model are
      operationalized (Fawcett, 1989). This article describes the first step in
      operationalizing the Corbin and Strauss Trajectory Model undertaken by the
      research team which resulted in the development of eight "Phase-specific
      protocols." Two of the eight phase-specific protocols are presented.

PMID- 8153495
TI  - Nursing as aesthetic experience and the notion of practice.
AB  - The notion of practice, traditionally understood as the creative and skillful
      application of knowledge, can be broadened if nursing caregiving is viewed as a
      lived aesthetic experience. The philosophical connection between practice and
      aesthetic experience is rooted in the professional values of care and excellence.
      The Aristotelian meanings of praxis, the notions of which include skillful
      action, excellence in conduct, and moral and political accountability are
      explored. These foundational values of nursing, the "felt" qualities of which are
      richly aesthetic, conduce an experience that is capable of intensifying and
      furthering meaning, and bringing about heightened awareness of consummatory
      ideals. Nursing practice, then, is open to a whole new interpretation: one that
      bears the gift of the real possibility for a unified experience--an experience
      that would integrate one's senses, thought, action, and the meaning and value of
      one's work. This way of understanding the idea of practice provides a useful
      alternative in thinking about nursing work, professional life, and the
      professional community.

PMID- 8153496
TI  - Recreational activities and degenerative joint disease.

PMID- 8153498
TI  - Adherence to exercise programmes. Recommendations.
AB  - Despite the widespread dissemination of information concerning the negative
      health consequences associated with sedentary living, adult physical activity in
      many industrialised nations remains well below recommended levels. Approximately
      50% of individuals who start an aerobic exercise programme will stop within the
      first 6 months, even though it is well known that to obtain the health benefits
      associated with physical activity, participation must be maintained. Programmes
      involving the use of behaviour management techniques appear to increase short
      term adherence to exercise. Recently, an adherence rate of greater than 95% over
      6 months was achieved in a large group of university employees who participated
      in aerobic training using a 'behavioural treatment packages' approach.
      Unfortunately, inconsistencies in the literature on definitions and measurement
      of adherence make valid comparisons among studies difficult. Also, long term
      follow-up of behavioural intervention methods and their effect on exercise
      adherence is generally lacking. It is likely that strategies to increase physical
      activity participation in the general population will demand multiple levels of
      intervention (personal, organisational, environmental and societal) if they are
      to succeed in the long term.

PMID- 8153497
TI  - Acute and chronic response of skeletal muscle to resistance exercise.
AB  - Skeletal muscle tissue is sensitive to the acute and chronic stresses associated
      with resistance training. These responses are influenced by the structure of
      resistance activity (i.e. frequency, load and recovery) as well as the training
      history of the individuals involved. There are histochemical and biochemical data
      which suggest that resistance training alters the expression of myosin heavy
      chains (MHCs). Specifically, chronic exposure to bodybuilding and power lifting
      type activity produces shifts towards the MHC I and IIb isoforms, respectively.
      However, it is not yet clear which training parameters trigger these differential
      expressions of MHC isoforms. Interestingly, many programmes undertaken by
      athletes appear to cause a shift towards the MHC I isoform. Increments in the
      cross-sectional area of muscle after resistance training can be primarily
      attributed to fibre hypertrophy. However, there may be an upper limit to this
      hypertrophy. Furthermore, significant fibre hypertrophy appears to follow the
      sequence of fast twitch fibre hypertrophy preceding slow twitch fibre
      hypertrophy. Whilst some indirect measures of fibre number in living humans
      suggest that there is no interindividual variation, postmortem evidence suggests
      that there is. There are also animal data arising from investigations using
      resistance training protocols which suggest that chronic exercise can increase
      fibre number. Furthermore, satellite cell activity has been linked to myotube
      formation in the human. However, other animal models (i.e. compensatory
      hypertrophy) do not support the notion of fibre hyperplasia. Even if hyperplasia
      does occur, its effect on the cross-sectional area of muscle appears to be small.
      Phosphagen and glycogen metabolism, whilst important during resistance activity
      appear not to normally limit the performance of resistance activity. Phosphagen
      and related enzyme adaptations are affected by the type, structure and duration
      of resistance training. Whilst endogenous glycogen reserves may be increased with
      prolonged training, typical isotonic training for less than 6 months does not
      seem to increase glycolytic enzyme activity. Lipid metabolism may be of some
      significance in bodybuilding type activity. Thus, not surprisingly, oxidative
      enzyme adaptations appear to be affected by the structure and perhaps the
      modality of resistance training. The dilution of mitochondrial volume and
      endogenous lipid densities appears mainly because of fibre hypertrophy.

PMID- 8153499
TI  - Shoulder pain in tennis players.
AB  - Shoulder pain is a common complaint amongst tennis players. The anatomy of the
      shoulder girdle is complex and defining the exact pathology that accounts for
      shoulder pain in tennis players can be difficult. Impingement syndrome and
      glenohumeral instability are the 2 most common causes of shoulder pain in tennis
      players. Tennis players with impingement syndrome typically present with pain,
      especially during overhead strokes and serves. The impingement test helps to
      confirm the diagnosis. Treatment focuses on restoring any motion and strength
      deficits and anterior acromioplasty with repair of rotator cuff tears for
      patients who do not respond to nonoperative care. Tennis players with instability
      present with pain and a sensation of shoulder 'slipping'. Treatment emphasises
      rotator cuff and scapular muscle strengthening and surgical stabilisation of the
      capsulo-labral complex for patients who fail a rehabilitation programme.
      Prevention of injury in tennis players depends on maintaining flexibility,
      strength and synchrony among the glenohumeral and scapular muscles.

PMID- 8153503
TI  - [Sexuality in old age].
AB  - The research on sexual behavior of old people is still suffering from grave
      deficits. In spite of this it can be said that the biological bases in men and in
      women are characterized by lower speed and intensity. The old people's attitude
      towards sexuality in general and their own sexuality is still less liberal than
      the attitude of younger persons. The frequency of sexual intercourse decreases,
      mainly because of lack of partners or because of health problems. There are many
      other forms of sexual behavior; especially, the importance of tenderness is
      increasing. A theoretical model of factors influencing the sexuality in old age
      is presented. Practical considerations concerning the prevention in young and in
      older people, treatment of older people in the physician's practice and their
      living in institutions conclude the article.

PMID- 8153502
TI  - [Importance of and need for vitamins in old age].
AB  - Vitamins may modulate primary as well as secondary processes of aging. On the
      other hand, vitamin metabolism itself may be modified by the process of aging or
      by various chronic diseases connected with aging. On the basis of these multiple
      interactions the question arises whether the demand for individual vitamins is
      altered as a consequence of aging. Age-dependent metabolic changes may alter the
      need for individual vitamins. This is the case for vitamin D, vitamin B6,
      Riboflavine, and in special subpopulations for vitamin B12. The most important
      source for a sufficient supply of vitamins is an adequate nutrition. Thus,
      besides the aforementioned vitamins, insufficient alimentary intake with food
      plays the most important role in vitamin deficiency in the elderly. Due to age
      specific alterations of the vitamin-A metabolism, toxicity of vitamin-A plays a
      more important role than vitamin-A deficiency. The vitamins A and D as well as
      vitamin C are discussed in detail.

PMID- 8153501
TI  - Tarsal navicular stress fracture in athletes.
AB  - Stress fracture of the tarsal navicular bone is now frequently recognised. The
      majority of navicular stress fractures are partial fractures in the sagittal
      plane. They occur mainly in track and field athletes. A number of theories
      regarding the aetiology of this fracture have been proposed. Athletes with a
      history of vague, activity-related midfoot pain, with associated tenderness over
      the dorsal proximal navicular ('N' spot) should be suspected of having a
      navicular stress fracture. Plain radiography frequently fails to demonstrate the
      fracture, thus radionuclide scanning is the investigation of choice to detect
      navicular stress injury. A computed tomography (CT) scan should be performed to
      confirm the presence of the fracture. Various methods of treatment have been
      employed. A minimum of 6 weeks of strict non-weightbearing cast immobilisation is
      the treatment of choice. After removal of the cast, a further 6 week programme of
      rehabilitation with a graduated return to activity, joint mobilisation and soft
      tissue massage is required. Surgery for nonunion or delayed union is rarely
      required if initial treatment is appropriate.

PMID- 8153504
TI  - [Geriatric dentistry: medical problems as well as disease- and therapy-induced
      oral disorders].
AB  - As in pediatric dentistry, management of the oral problems in elderly patients
      does not depend on the development of new technical skills, but rather on the
      knowledge of: biological, psychological and social aspects of primary
      (physiological or age-related) and secondary (pathological or disease-related)
      aging; atypical presentations of disease; multiple pathological conditions
      (polymorbidity, polypathophysiology, polypharmacy); an underreporting of disease;
      the importance of functional status; the role of an interdisciplinary team;
      Geriatric medicine refers to social, psychological and clinical aspects of
      disease in older adults. Geriatric dentistry deals with the respective aspects
      concerning oral diseases. Chronic conditions as well as their treatment (e.g.
      medication) are more common with advancing age. They may have major implications
      for dental practice, leading to changes in oral health behavior and attitudes of
      the elderly patient with sometimes detrimental effects on oral health. Therefore,
      different concepts in prevention, diagnosis and therapy of oral diseases are
      required for the oral care of older adults. Two important consequences must be
      considered: Firstly, the medical education of the dentist and the dental team
      must be improved. The dental team must become a member of the group of health
      care professionals caring for an aging population (geriatric medicine) to meet
      the heterogeneous needs of as much as 75% of our future patients. Secondly, there
      is great need for education of all health-care professionals dealing with elderly
      patients about possible negative impacts medicine can have on oral health.
      Identification and diagnosis of oral disease as well as preventive measures must
      be stressed.

PMID- 8153505
TI  - [Cardiovascular interventions in elderly patients].
AB  - From January 1981 to December 1990, 204 patients between 70 and 81 years of age
      underwent aortocoronary bypass-surgery, and 20 patients age 80 years or older
      underwent valvular surgery. The operative mortality rate (30-day mortality) of
      aortocoronary bypass-surgery was 6.8%; actuarial survival rate at 1 and 5 years
      was 92% and 86%, respectively. The operative mortality rate of valvular surgery
      was 15%; actuarial survival rate at 1 and 5 years was 78.5% and 67%,
      respectively. The mean follow-up was 25 months. Most patients undergoing
      myocardial revascularization (71%) and all the patients undergoing valvular
      surgery were preoperatively in New York Heart Association (NYHA) functional class
      III or IV, at the end of the follow-up in NYHA functional class I or II (95%). A
      rapid rise in the number of heart operations in the elderly is evident. It is
      associated with increased but acceptable operative risk. Longterm results and
      postoperative improvement of functional status are satisfactory.

PMID- 8153506
TI  - [Urinary incontinence in geriatrics].
AB  - While incontinence is common in the elderly, it is not normal. The physiologic
      and pathologic changes that occur with aging predispose the older individuals to
      becoming incontinent, but it is the addition of further insults that precipitates
      incontinence. Incontinence in the elderly is usually multifactorial in nature and
      must be approached in a comprehensive manner, so that all reversible causes are
      identified and treated, serious lesions are excluded and targeted therapy may be
      prescribed (1).

PMID- 8153500
TI  - Physical activity and lipoprotein lipid disorders.
AB  - Working muscle plays a central role in the control of lipid metabolism. Increased
      physical activity induces a number of positive changes in the metabolism of
      lipoproteins: serum triglycerides are lowered by the increased lipolytic activity
      and the production of native high density lipoprotein (HDL) particles is
      increased. The increased lecithin: cholesterol acyltransferase activity leads to
      an increased production of HDL2, which in addition is catabolised more slowly due
      to a decreased activity of hepatic lipase. The 3 effects explain the increased
      HDL levels of endurance trained individuals. These effects have been demonstrated
      in cross-sectional as well as longitudinal studies by different groups, and can
      be induced by training, independent of changes in bodyweight. The influence of
      endurance activity on the quality and quantity of low density lipoprotein (LDL)
      particles is a further reason for the antiatherogenic potential of increased
      physical activity. It has been shown by several groups that small dense LDL
      particles represent a particular risk factor for atherosclerosis. Recent studies
      presented strong evidence that LDL level and composition can be influenced
      favorably by physical activity. In addition to the direct influence of physical
      activity on lipids and lipoproteins, physical exercise may improve the
      disturbances of haemorheological factors, particularly those associated with
      hypertriglyceridaemia. In conclusion, there is increased evidence that physical
      activity is able to favourably influence all 3 components of the atherogenic
      lipoprotein phenotype: the HDL concentration increases, the concentration of
      small dense LDL decreases, and serum triglycerides are reduced.

PMID- 8153507
TI  - [Assessment of parathyroid gland function: predictive value of a nomogram].
AB  - Recent developments in measurement of intact parathormone (PTH) has enabled to
      generate a nomogram for parathyroid function. Blood levels of PTH can thus be
      interpreted in relation to calcemia. Intact PTH and calcium were assayed in blood
      from 99 healthy subjects studied under fasting conditions; 26 subjects were also
      studied during hyper- and hypocalcemia, induced by calcium and EDTA infusions,
      respectively. Serum levels of intact PTH which had been obtained in 99 patients
      were then analysed retrospectively by comparison with the nomogram. Patients
      whose intact PTH levels lie above the normal zone of the nomogram produce too
      much PTH relative to the blood calcium level (hyperparathyroidism); those falling
      under the normal zone produce too little (hypoparathyroidism).

PMID- 8153508
TI  - [Reconstruction of segmental bone defects using massive osseous and
      osteocartilaginous allograft].
AB  - The reconstruction of large segmental defects after the resection of malignant
      bone tumors is usually done with modular or custom-made endoprostheses, so far,
      they appear to work well. From the experience with other indications for
      endoprostheses it must be admitted that failures will be a matter of time only.
      With the improved prognosis for patients with primary malignant bone tumors with
      regard to relapse-free survival and increased chances for permanent cure, the
      trend for reconstruction procedures should be directed to more 'biological'
      techniques. The reconstruction of osseous and osteocartilaginous defects with
      massive allografts is somewhere between the use of autologous bone and artificial
      replacement. From the experience with 14 allograft reconstructions in primary
      malignant bone tumors (osteosarcoma, malignant fibrous histiocytoma,
      leiomyosarcoma, chondrosarcoma, lymphoma) or other aggressive lesions (aneurysmal
      bone cyst, recurring giant-cell tumor, solitary metastasis) of the humerus (one
      osteoligamentous graft in combination with an endoprosthesis, one intercalary
      graft), the femur (three intercalary grafts, two osteoarticular distal femurs,
      one combination with an endoprosthesis), and the proximal tibia (four
      osteocartilaginous, two intercalary grafts) in patients aged 10 to 64 years, we
      feel that this type of reconstruction allows for a reconstruction without
      sacrificing more bone and soft tissue than needed for the surgical margins.
      Fusion between the patient's bone and the allograft has been seen after 6 to 18
      months. From this small series it is concluded that using allografts might allow
      for the preservation of joint structures that need to be resected for the
      implantation of an endoprosthesis, increasing the possibilities for salvage
      procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153509
TI  - [Subjective tolerance to transesophageal echocardiography].
AB  - Transesophageal echocardiography (TEE) is a new semi-invasive diagnostic tool in
      cardiology. We studied tolerance of TEE. 95 out of 121 consecutive patients were
      interviewed using a detailed, structured questionnaire (42 questions). Most
      patients (97%) received midazolam prior to TEE. TEE was tolerated well by 89% (n
      = 84) of the patients. Patients receiving a higher dose of midazolam (> 0.04
      mg/kg bodyweight) tolerated TEE better than those in the lower-dose group (p <
      0.0005), but they experienced side effects more often (p < 0.05) and did not
      tolerate fatigue as well (p < 0.0005). TEE was tolerated less well by younger
      patients (age < or = 45 years); they experienced more often local irritation than
      older patients due to the endoscope (52% versus 20% in older patients, p < 0.005)
      and complained more often about dysphagia (70% versus 24%) and sore throat (60%
      versus 19%) (p < 0.0005) after TEE. Patients < or = 45 years reported more side
      effects by midazolam than older patients, such as palpitations (30% versus 2%),
      hiccups (17% versus 0%), poor concentration (20% versus 3%), nausea (13% versus
      2%), ataxia (17% versus 3%) or fatigue (88% versus 59%) (p < 0.05 to 0.0005).
      Females were more often afraid of TEE (53%) and the endoscope (56%) than males
      (35% and 23%, p < 0.08 and p < 0.002) and also disliked the endoscope more often
      (42%) than men (19%, p < 0.03). Some women complained about headaches after TEE
      (10%), whereas men did not (p < 0.05). Thus, TEE, after premedication with
      midazolam, is subjectively well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153510
TI  - [A case from practice (288)].

PMID- 8153511
TI  - Preparing for a comfortable life-style after retirement.

PMID- 8153512
TI  - Versatile uses for plunger attachments.
AB  - Plunger attachments are among the simplest of all attachments, yet they are
      extremely versatile. When basic design principles are followed, plunger
      attachments can be employed to solve diverse restorative situations.

PMID- 8153513
TI  - Light-cured dimethacrylate ocular prosthesis.
AB  - The use of a visible light-cure dental synthetic resin offers some advantages in
      the clinical delivery of an ocular prosthesis and a statistically significant
      reduction in the processing time.

PMID- 8153514
TI  - [The cardiovascular risk in adolescents. Nursing evaluates and intervenes].

PMID- 8153515
TI  - [Emergencies. Prehospital care].

PMID- 8153517
TI  - [Nursing and communication].

PMID- 8153516
TI  - [The emotional response to the stress of work].

PMID- 8153518
TI  - [Accidents among schoolchildren. Care at a primary care center].

PMID- 8153519
TI  - [Examination diets for diagnostic tests].

PMID- 8153520
TI  - [Thoracoscopy].

PMID- 8153521
TI  - [Care in the preoperative period].

PMID- 8153522
TI  - [The symptoms of hypoglycemia. Can they be clearly described?].

PMID- 8153523
TI  - [Bandages (II)].

PMID- 8153525
TI  - [Limiting care ought not to mean necessarily limiting health].

PMID- 8153524
TI  - [Continuing education. 85. Health education. The danger of self medication].

PMID- 8153526
TI  - [Symptomatology of ischemic carotid complications].
AB  - Clinical features of the carotid artery syndromes are reviewed. Limited
      infarction cause typical clinical syndromes. However, in most cases, embolic
      occlusion is multiple and produces various clinical syndromes.

PMID- 8153527
TI  - [Ultrasonic study of the internal carotid artery].
AB  - Investigation of the internal carotid arteries by ultrasound has revolutionized
      the prescription of complementary examinations in ischemic cerebral accidents.
      There are four techniques: 1) continuous Doppler, 2) CT scan with classical
      Doppler 3) CT scan with colour Doppler and 4) transcranial Doppler. The
      complementary of these investigations makes it possible to obtain hemodynamic and
      morphological information on the internal carotid artery from its cervical origin
      to its intracranial terminal. Reliable diagnosis of atherosclerotic carotid
      stenoses and occlusions has considerably reduced the need for angiography.
      Intracranial circulation can be studied by transcranial Doppler. This technique
      allows evaluation of the hemodynamic influence of extracranial carotid stenoses
      and occlusions, and diagnosis of hemodynamic stenoses in the intracranial
      internal carotid artery. Assessment of the thickness of the intima plus tunica
      media of the primary carotid artery by CT scan appears to be a sensitive marker
      of cerebral and coronary ischemic risk.

PMID- 8153528
TI  - [Radiological study of the internal carotid artery].
AB  - Three radiologic methods are used to investigate the internal carotid artery. The
      main indication of CT scan is the assessment of brain ischaemic complications of
      carotid disease. Magnetic resonance imaging allows in addition to detect
      dissecting hematomas and carotid flow abnormalities. Cerebral angiography, which
      owes much to the advent of digital techniques, remains the standard examination
      of internal carotid artery. Complications of angiography although rare and
      usually benign explain the recent development of less invasive explorations such
      as dynamic CT scan and magnetic resonance angiography. This latter method is
      still under evaluation for diagnosis of carotid stenosis and small size
      aneurysms.

PMID- 8153529
TI  - [Study of the effect of internal carotid artery diseases on cerebral
      hemodynamics].
AB  - The cerebral artery system is richly anastomosed. These anastomoses can
      compensate for the effects of a stenosis or an occlusion of the internal carotid
      artery. In addition, control of cerebral blood flow occurs via a double process
      of haemodynamic and metabolic adaptation to a drop in perfusion pressure. Direct
      or indirect measurement of the cerebral perfusion reserve can evaluate the
      haemodynamic effects of an internal carotid stenosis.

PMID- 8153530
TI  - [What are high-risk atherosclerotic carotid stenoses?].
AB  - Atherosclerotic carotid stenosis carry a double risk: local, of ipsilateral
      stroke, and general, of myocardial infarction and vascular death. The local risk
      is mainly correlated with the presence of relevant symptoms and with the degree
      of stenosis. It is virtually absent in stenosis < or = 30% but reaches 17% per
      year in symptomatic stenosis > or = 90%. The other factors which increase the
      local risk are: the progression of stenosis, the presence of ulceration, the
      extent of atherosclerosis (contralateral carotid occlusion, ischemic heart
      disease), the number and severity of vascular risk factors. The general risk is
      mainly cardiac and is related more to the extent and severity of the underlying
      atherosclerotic disease than to the morphology of stenosis or the presence of
      symptoms. This also holds true for the surgical risk, which is, in addition,
      heavily related to the technical conditions of the operation. The treatment of a
      patient with carotid stenosis should be discussed on a case by case basis.
      Medical treatment applies to all stenoses whereas surgery applies only to
      stenoses which carry a high local risk and a low general and surgical risk. The
      efficacy of surgery is thus maximal in the group of high symptomatic stenosis.

PMID- 8153531
TI  - [Results of clinical trials evaluating the surgery of carotid stenoses].
AB  - The usefulness of carotid endarterectomy remained unsettled until 1991, although
      it was one of the most widespread surgical interventions. Its indications are now
      being scientifically established by means of perspective and randomized clinical
      trials comparing endarterectomy to medical therapy in patients with internal
      carotid artery atherosclerosis. The results of 2 trials (CASANOVA, VACS#167)
      performed in asymptomatic patients suggest that there is no evidence that carotid
      endarterectomy might be of benefit in such patients; however both studies had
      serious methodological problems that will probably be resolved by a large on
      going study (ACAS). The results of 3 trials performed in patients with recent
      transient ischemic attacks or stroke in the internal carotid artery territory
      suggest that: (1) carotid endarterectomy is of benefit in patients with a degree
      of stenosis higher than 70%; (2) carotid endarterectomy is not of benefit in
      patients with a degree of stenosis smaller than 30%; (3) the best therapeutic
      strategy remains unsettled in patients with a 30-70% degree of stenosis and in
      patients examined more than 6 months after neurological deficits.

PMID- 8153532
TI  - [Technical aspects of the surgery of atherosclerotic carotid stenoses].
AB  - The aim of the present paper is to present a brief critical analysis of the
      technical aspects of surgery for atherosclerotic carotid stenoses, including
      reconstructive techniques, preoperative evaluation of neurologic risk and
      intraoperative monitoring and cerebral protection. Our present personal protocol
      is presented.

PMID- 8153533
TI  - [Medical treatment of atherosclerotic carotid stenoses].
AB  - Patients with atherosclerotic carotid artery stenosis commonly have arterial
      disease elsewhere, especially coronary artery disease. The aim of the medical
      treatment is to reduce the incidence of stroke, myocardial infarction and
      vascular death. Both primary and secondary prevention of these vascular events
      requires control of vascular risk factors, particularly lowering elevated blood
      pressure, lowering of elevated blood cholesterol and stopping smoking. Aspirin
      and ticlopidine are effective in reducing vascular events in patients with
      atherosclerosis, with a relative reduction of about 25% for the composite outcome
      event "stroke, myocardial infarction or vascular death". Whether low dose (less
      than 100 mg/d), medium (300 mg/d) or high dose (1,000 mg/d or more) of aspirin
      confer the same degree of protection against vascular events is unclear. The
      gastrointestinal side effects are greater for the high dose than for the medium
      dose, but the difference between the medium dose and the low dose is very small.
      Ticlopidine conveys a modest risk of reversible severe neutropenia and is often
      used as a second-line drug, but this is a controversial issue. Heparin is often
      used as a short-term preventive treatment in patients with transient ischaemic
      attacks or minor stroke, especially in those with "crescendo" transient ischaemic
      attacks, progressing stroke, severe carotid stenosis or intraluminal thrombus.

PMID- 8153534
TI  - [Internal carotid artery dissection].
AB  - Arterial dissection results from bleeding into the vessel wall. Some cases are
      associated with cervical trauma or have evidence of an underlying vascular
      disease; many occur without any history of injury or detectable arterial disease.
      Among the cervical cephalic arteries, the extracranial segment of the internal
      carotid artery is the vessel most commonly involved; intracranial carotid
      dissections are much rare. Carotid dissection occurs predominantly in young or
      middle-aged adults and shows no sex predominance. Although clinical
      manifestations can be extremely diverse (from isolated headache to rapidly lethal
      stroke), the most common and suggestive syndrome associates "local" symptoms
      (such as head or neck pain, Horner's syndrome, pulsatile tinnitus or lower
      cranial nerves palsy) and delayed (up to several weeks) symptoms of cerebral
      ischaemia in the territory of the internal carotid artery territory. Dissection
      can be bilateral or associated with dissection of the vertebral artery.
      Angiography has long been considered the gold standard for the diagnosis. As this
      procedure carries a risk of cerebral complications, noninvasive diagnostic
      approaches such as magnetic resonance imaging and ultrasound have been developed
      and are increasingly used. The prognosis of carotid dissections depends on the
      presence and severity of ischaemic brain damage. Recurrent dissections seem
      extremely rare. Normalization or improvement of the vascular abnormalities during
      the subsequent weeks is frequent and is an excellent argument in favour of the
      diagnosis. Although no controlled trial has ever been performed, anticoagulant
      treatment is often used for a few months when the dissection involves the
      extracranial segment of the carotid artery. No standard treatment of intracranial
      carotid dissection has emerged.

PMID- 8153535
TI  - [Rare lesions of the internal carotid arteries].
AB  - The rare lesions of internal carotid arteries are varied in both their appearance
      and their cause. Schematically, in addition to congenital anomalies, of which
      fibromuscular dysplasia is no doubt the most frequent, should be noted lesions of
      inflammatory, infectious, traumatic and iatrogenic origin. The fact that the
      relationship between some of these lesions and cerebral vascular accidents is not
      clearly established, leads to diagnostic and therapeutic problems which are
      difficult to resolve.

PMID- 8153536
TI  - [Endovascular treatments of internal carotid artery diseases].
AB  - Rapid progress has recently been made in endovascular treatment of the internal
      carotid artery, with little-invasive, new interventions often replacing, or
      facilitating, surgery. Treatments of aneurysms, tumoural embolisation and
      haemostasis are well established. Promising techniques for revascularisation
      (fibrinolysis, dilatation) are under evaluation. We discuss their interest and
      respective indications.

PMID- 8153537
TI  - [Role of the p53 gene in human malignant tumors. A major discovery in oncology].

PMID- 8153538
TI  - [Intestinal coccidiosis. Parasites dangerous to immunosuppressed patients].

PMID- 8153539
TI  - [Hypercorticism. Physiopathology, clinical and biological diagnosis].

PMID- 8153540
TI  - [Antibiotics. General data on modes of action and mechanisms of resistance].

PMID- 8153541
TI  - [Broncho-alveolitis in infants. Diagnosis, treatment].

PMID- 8153542
TI  - [Diabetic retinopathy. Physiopathology, diagnosis, course and prognosis,
      treatment].

PMID- 8153543
TI  - [Acute pericarditis. Etiology, diagnosis, course, complications, treatment].

PMID- 8153544
TI  - [Rheumatoid arthritis. Pathological anatomy, course, diagnosis, treatment].

PMID- 8153545
TI  - [Hyperprolactinemia. Physiopathology, diagnosis, treatment].

PMID- 8153546
TI  - [Aneurysmal cyst of the maxilla. Apropos of a case].
AB  - A case of extensive aneurysmal bone cyst of the maxilla is described, with a
      recurrence 2 years after surgical curettage, treated by new curettage and
      radiotherapy. The pathogenesis of this pseudo-cyst is yet obscure. While CT (and
      MR) demonstrate characteristic fluid-fluid levels, the diagnosis remains
      histological. A long survey, based on radiography, is necessary to detect
      recurrence.

PMID- 8153547
TI  - [Malignant granuloma of the face and angiocentric T-cell lymphoma. A review of
      the literature apropos of a case].
AB  - The authors report the observation of a lethal midline granuloma in a 43 years
      old man, at first seen with repeated left sinusitis disease, the histo
      pathological study of a biopsy of the external middle third of the left side of
      the nose made the diagnosis of midline lethal granuloma, classically called
      Stewart granuloma by french authors. General Medical Investigations to find some
      peripheral extension, done in specialized services were negative, Epstein Barr
      DNA was not found by the immuno-histochemical investigations and so don't prove
      the filiation of this case with angiocentric T cell immunoproliferative lesion.
      By the light of this observation and of a literature review, the authors debate
      about the difficulty of diagnosis and about the relations with the other
      granulomatosis lesions of the face, non Hodgkins' lymphoma and angiocentric T
      cell immuno-proliferative lesions.

PMID- 8153548
TI  - [Michel Dechaume (23 February 1897-19 October 1991)].

PMID- 8153549
TI  - [Temporomandibular compression due to condylar osteochondroma].
AB  - We describe in this work one case of osteochondroma of the mandibular condyle.
      The first clinical sign was a limitation of the mouth opening. Based on this
      lesion, a review of the literature is made, and different treatment modalities
      are discussed.

PMID- 8153550
TI  - [Combined epithelial odontogenic tumor].
AB  - The "combined epithelial odontogenic tumor" in an uncommon lesion characterized
      by the synchronous presentation of typical histological feature of the
      adenomatoid odontogenic tumour, and the Pindborg's tumor. In this work, the
      authors, describe a case of combined epithelial odontogenic tumor associated with
      an unerupted maxillary central incisor. The clinical and histological
      characteristics of this lesion point out that it could be primitively an
      adenomatoid odontogenic tumor, with several areas of calcifying epithelial
      odontogenic tumor.

PMID- 8153551
TI  - [A trans-parotid approach to the osteosynthesis of fractures of the mandibular
      condyle. A study apropos of 30 cases].
AB  - The authors report a homogeneous series of 30 cases with fractures of the
      mandibular condyles treated by internal fixation with a mini-plaque via the
      transparotidial route. The patient were treated between 1987 and 1992, with a
      minimum follow-up of one year. The transparotidial route has the reputation of
      being dangerous because of the proximity of the facial nerve and the poor
      vascular supply to the condyle. It is described in detail. Indications are
      exclusively extra-articular fractures. Complications were observed although no
      definitive facial nerve paralysis was seen. The authors conclude that the best
      indications are subcondylian fractures with or without luxation. In cases with
      luxation, it is important to verify the menisco-ligament system simultaneously.
      The authors emphasize the complementary nature of this treatment with the
      functional method.

PMID- 8153552
TI  - [Orthodontic repositioning technic of impacted lower 2nd molars].
AB  - Author explains an orthodontic appliance which permits uprighting of horizontal
      impacted mandibular second molar teeth, associating a mandibular anchorage and an
      uprighting auxiliary spring. The anchorage consist in a Mollin lower lingual
      arch. The auxiliary spring will upright the tooth in two steps. First one, it
      will induce a distal movement of the second molar. Second one it will induce the
      crown tipping. The significant benefit of this appliance is to permit an only
      orthodontic approach, without necessity of any surgical assistance.

PMID- 8153553
TI  - [Pierre Cernea (6 April 1910-19 October 1991)].

PMID- 8153555
TI  - [Chronic luxation of the mandible. Apropos of 2 recent cases].
AB  - The authors report two recent cases of intractable luxation of the
      temporomandibular joint which was initially overlooked due to the neurologic or
      geriatric context. Open reduction was performed. The literature is reviewed and
      the different aetiological forms of the long standing luxations are presented
      together with the different treatments proposed.

PMID- 8153554
TI  - [Changes in the periodontal alveolar bone after surgical restoration of the
      dental occlusion].
AB  - Alveolar cortical bone of 49 including teeth of patients with dento-facial
      deformities has been studied before and after procedures of orthognathic surgery,
      performed to give a correct occlusion of those teeth. Standardised radiographic
      technic was used to measure the width of cortical alveolar lamina. The width was
      increased in all teeth studied, in a variable degree. This augmentation was
      explained as morphologic changes to maintain physiologic conditions in teeth's
      function.

PMID- 8153556
TI  - The efficacy of a multichannel hearing aid in which the gain is controlled by the
      minima in the temporal signal envelope.
AB  - A multichannel signal-processing hearing aid in which the gain is controlled by
      the level of the minima in the sound envelope [outlined by Festen et al., 1990]
      was evaluated with hearing-impaired listeners. This evaluation is an extension to
      the work reported by van Dijkhuizen et al. (1990). A first experiment focused on
      the speech-reception threshold (SRT), i.e. the S/N ratio for 50% intelligibility.
      The greatest benefit in terms of the SRT from frequency-dependent control of the
      amplification is expected in conditions where the spectrum of noise exceeds
      strongly that of the speech in a limited frequency region. In these conditions
      frequency-dependent amplification may reduce upward spread of masking. We
      investigated the upper limit of this benefit in conditions of intense frequency
      limited interfering noise. Speech and noise were both spectrally shaped according
      to the line bisecting the listener's dynamic range; however, the level of the
      noise in one octave band (0.25-0.5 or 0.5-1 kHz) was increased by 20 dB. The
      results show that frequency-selective attenuation of the signal in the octave
      band with the 20-dB increase of noise is more beneficial than wide-band gain
      control, and gives a decrease in SRT of up to 4 dB relative to a condition
      without gain control. In a subsequent experiment we investigated, for several
      very common interfering sounds, the effect of controlling the gain by the minima
      in the signal envelope on both the SRT and the perceived noisiness. Results show
      that the condition with gain control does not affect the SRT for sentences in the
      presence of everyday interfering sounds having spectra that are roughly
      comparable to that of the speech signal; however, it substantially reduces the
      perceived noisiness. In line with our expectations, the effect of the gain
      control on the signal was very small for a single voice, and it was greatest in
      case of sounds with a more or less continuous character (e.g. stationary noise,
      music). For these last sounds it was found that the growth in perceived noisiness
      with the increase of input level is equivalent to the growth produced by only
      about one-fifth of the increase in input level (in decibels) in a condition
      without gain control.

PMID- 8153557
TI  - Auditory pattern perception in the profoundly hearing impaired and lipreading of
      Dutch phonemes.
AB  - Successful rehabilitation of the profoundly hearing impaired by means of a speech
      processing hearing aid requires integration of auditory and visual speech
      information. In two studies we investigated (1) which perceptual dimensions play
      a role in processing various auditory patterns by profoundly hearing-impaired
      subjects, and (2) which Dutch consonants and vowels can be identified by the
      average lipreader. One of the important cues in auditory pattern discrimination
      seems to be the presence of temporal fluctuations (beats) in the signal,
      resulting from two closely placed frequency components. However, this feature is
      confounded with the perception of loudness. A second cue used by some subjects is
      the presence of high-frequency peaks. In lipreading, at least three groups of
      consonants and three vowel groups may be distinguished; phonemes within a group
      cannot be discriminated from each other. Important features for both consonants
      and vowels are degree of lip opening and lip activity (movement or rounding).
      These results suggest how the auditory speech signal might be coded so as to
      provide supplementary information to speechreading.

PMID- 8153558
TI  - New developments in speech pattern element hearing aids for the profoundly deaf.
AB  - Two new developments in speech pattern processing hearing aids will be described.
      The first development is the use of compound speech pattern coding. Speech
      information which is invisible to the lipreader was encoded in terms of three
      acoustic speech factors; the voice fundamental frequency pattern, coded as a
      sinusoid, the presence of aperiodic excitation, coded as a low-frequency noise,
      and the wide-band amplitude envelope, coded by amplitude modulation of the
      sinusoid and noise signals. Each element of the compound stimulus was
      individually matched in frequency and intensity to the listener's receptive
      range. Audio-visual speech receptive assessments in five profoundly hearing
      impaired listeners were performed to examine the contributions of adding
      voiceless and amplitude information to the voice fundamental frequency pattern,
      and to compare these codings to amplified speech. In both consonant recognition
      and connected discourse tracking (CDT), all five subjects showed an advantage
      from the addition of amplitude information to the fundamental frequency pattern.
      In consonant identification, all five subjects showed further improvements in
      performance when voiceless speech excitation was additionally encoded together
      with amplitude information, but this effect was not found in CDT. The addition of
      voiceless information to voice fundamental frequency information did not improve
      performance in the absence of amplitude information. Three of the subjects
      performed significantly better in at least one of the compound speech pattern
      conditions than with amplified speech, while the other two performed similarly
      with amplified speech and the best compound speech pattern condition. The three
      speech pattern elements encoded here may represent a near-optimal basis for an
      acoustic aid to lipreading for this group of listeners. The second development is
      the use of a trained multi-layer-perceptron (MLP) pattern classification
      algorithm as the basis for a robust real-time voice fundamental frequency
      extractor. This algorithm runs on a low-power digital signal processor which can
      be incorporated in a wearable hearing aid. Aided lipreading for speech in noise
      was assessed in the same five profoundly hearing-impaired listeners to compare
      the benefits of conventional hearing aids with those of an aid which provided MLP
      based fundamental frequency information together with speech+noise amplitude
      information. The MLP-based pattern element aid gave significantly better
      performance in the reception of consonantal voicing contrasts from speech in pink
      noise than that achieved with conventional amplification and consequently, it
      also gave better overall performance in audio-visual consonant
      identification.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8153559
TI  - A pilot experiment on the effects of an acoustically applied reduced speech
      signal on speechreading.
AB  - The aim of this study was to investigate how speechreading of short sentences
      could be enhanced by presenting the acoustic signal with real-time extracted
      supplementary speech features. The features were second format frequency and
      voiceless frication. A group of 10 normal-hearing subjects participated in a
      simulation experiment. Speechreading performance increased from 22.2% for
      speechreading only (pretraining), to 61.5% for speechreading plus supplementary
      auditory information (post-training). The gain from the acoustic information
      turned out to be larger for subjects who also performed better in the
      speechreading-only condition. No significant effect was found for the training
      volume (i.e. 30 minutes versus 5 hours).

PMID- 8153560
TI  - Speech discrimination via cochlear implants with two different digital speech
      processing strategies: preliminary results for 7 patients.
AB  - The following processing strategies have been implemented on an experimental
      laboratory system of a cochlear implant digital speech processor (CIDSP) for the
      Nucleus 22-channel cochlear prosthesis. The first approach (PES, Pitch Excited
      Sampler) is based on the classical channel vocoder concept whereby the time
      averaged spectral energy of a number of logarithmically spaced frequency bands is
      transformed into appropriate electrical stimulation parameters for up to 22
      electrodes. The pulse rate at any electrode is controlled by the voice pitch of
      the input speech signal. The pitch extraction algorithm calculates the
      autocorrelation function of a lowpass-filtered segment of the speech signal and
      searches for a peak within a specified time window. A random pulse rate of about
      150 to 250 Hz is used for unvoiced speech portions. The second approach (CIS,
      Continuous Interleaved Sampler) uses a stimulation pulse rate which is
      independent of the input signal. The algorithm scans continuously all specified
      frequency bands (typically between 4 and 22) and samples their energy levels.
      Evaluation experiments with 7 experienced cochlear implant users showed
      significantly better performance in consonant identification tests with the new
      processing strategies than with the subjects' own wearable speech processors
      whereas improvements in vowel identification tasks were rarely observed.
      Modifications of the basic PES- and CIS-strategies resulted in large variations
      of identification scores. Information transmission analysis of confusion matrices
      revealed a rather complex pattern across conditions and speech features. No final
      conclusions can yet be drawn. Optimization and fine-tuning of processing
      parameters for these coding strategies require more data both from speech
      identification and discrimination as well as psychophysical experiments.

PMID- 8153561
TI  - Directional hearing aid based on array technology.
AB  - The hearing impaired often have great difficulty understanding speech in
      surroundings with background noise or reverberation. A directional hearing aid
      might be beneficial in reducing background noise in relation to the desired
      speech signal. To this end microphone systems were developed with strongly
      directional characteristics, using array techniques. Considerable attention was
      paid to optimization and stability. Free-field simulations of several robust
      models showed that a directivity index of 9 dB can be obtained. Simulations were
      verified with a laboratory model. Based on simulations and measurements, two
      portable prototypes were developed and tested using a KEMAR-manikin. The KEMAR
      measurements showed that the two prototypes gave an improvement of the signal to
      noise ratio of 7 dB in a fully diffuse sound field. The benefit of these
      microphone arrays for the hearing impaired was tested in a sound insulated room.
      One loudspeaker was placed in front of the listener simulating the partner in a
      discussion, and a diffuse background noise was produced by eight loudspeakers
      placed on the corners of a cube. The hearing impaired subject was seated in the
      centre of the cube. The speech-reception threshold in noise for simple Dutch
      sentences was determined with a normal single omni-directional microphone and
      with one of the prototypes. The results of the listening tests with 45 hearing
      impaired subjects showed an average improvement of the S/N-ratio of 7.0 dB for
      monaural fitting.

PMID- 8153562
TI  - Binaural noise-reduction hearing aid scheme with real-time processing in the
      frequency domain.
AB  - A binaural noise-reduction algorithm for suppressing lateral noise sources was
      implemented in real-time and tested with normal and hearing-impaired subjects.
      With this algorithm, frequency bands with interaural time and amplitude
      differences characteristic for the "target" direction of the desired speech sound
      reach both ears without any attenuation. However, frequency bands with an
      interaural time and amplitude difference deviating from these desired values are
      attenuated. Speech quality assessments as well as speech intelligibility tests
      demonstrate a significant noise reduction of up to about 5 dB in signal-to-noise
      ratio for a dummy-head recorded "cocktail-party situation" in an anechoic
      chamber. For two additional acoustical situations, however, the subjective speech
      quality from the algorithm degrades with increasing reverberation, while the
      output from a real-time "dereverberation" algorithm was ranked higher with
      increasing reverberation. The results with hearing-impaired listeners suggest a
      combination of both algorithms, while stressing the importance of binaural
      listening and binaural hearing aids for the rehabilitation of impaired listeners
      in noisy environments.

PMID- 8153563
TI  - The design and testing of a noise reduction algorithm based on spectral
      subtraction.
AB  - Three noise reduction algorithms based on amplitude subtraction were designed and
      used to process speech mixed with babble noise in two signal-to-noise ratios. The
      estimation of the noise-magnitude spectrum was performed with a novel synchro
      method, which exploits specific characteristics of the speech signal. The
      unprocessed and processed signals were evaluated psychoacoustically by means of a
      four-alternative-forced choice test with monosyllabic words (minimal pairs) in
      carrier phrases. The testing was carried out on groups of normally hearing and
      hearing-impaired subjects and the long-term power spectra of the processed
      signals were shaped to be essentially identical with those from the corresponding
      unprocessed signals. For the hearing-impaired subjects all signals were
      spectrally shaped according to the POGO-fitting rule. None of the algorithms
      improved speech intelligibility for any group of listeners and no change in the
      overall pattern of confusion was observed.

PMID- 8153564
TI  - Evaluation of a noise reduction method--comparison between observed scores and
      scores predicted from STI.
AB  - Speech was mixed with different noise signals and then processed according to the
      well-known noise reduction method of 'spectral subtraction'. Three different
      algorithms were examined. The speech signals were subjected to a four alternative
      forced choice (4AFC) test. Both the processed and unprocessed signals were
      evaluated psycho-acoustically and objectively. Speech intelligibility was
      measured with the 4AFC test by presenting the signals via headphones to a group
      of normal-hearing and to a group of hearing-impaired listeners. The
      intelligibility scores were compared with the intelligibility scores predicted
      from a modified version of the Speech Transmission Index (STI). It appeared that
      although the noise reduction algorithms reduced the noise level, they did not
      improve the measured speech intelligibility, either for normal-hearing or for
      hearing-impaired listeners. This, however, was inconsistent with the scores
      estimated from STI, which erroneously predicted a significant improvement in
      intelligibility due to the noise reduction processing.

PMID- 8153565
TI  - Adaptive feedback stabilization of hearing aids.
AB  - A method is described for adaptively identifying and equalizing the feedback path
      of a hearing aid in order to stabilize the system. The algorithm utilizes an LMS
      adaptive filter and is implemented in digital form. An additional 10 to 15 dB of
      stable gain margin for a BTE hearing aid configuration has been demonstrated in
      laboratory experiments with hearing-impaired subjects using an interim custom
      VLSI circuit implementation.

PMID- 8153566
TI  - Comparison of a programmable 3-channel compression hearing system with single
      channel AGC instruments.
AB  - A commercially available programmable BTE hearing aid with 3-channel AGC
      (Siemens, Triton 3000) was compared to the subjects' own single-channel
      compression aids in a group of experienced hearing aid wearers. Two cross-over
      frequencies, three AGC onset levels, and three channel amplifications were
      programmable. The maximum output level was controlled by conventional peak
      clipping. The frequency response of the multichannel system was matched to the
      individuals' own aids which had been fitted in the two years prior to this study.
      Frequency response shaping was accomplished by real ear measurement monitoring.
      The performance of the hearing instruments was measured by (1) speech audiometry
      in noise and (2) subjective judgement of sound quality and speech
      intelligibility. Speech recognition was tested using rhyme test material in noise
      in a group of 10 subjects with sloping high-frequency hearing loss as well as in
      a group of 16 individuals with nearly flat audiograms. In both subgroups speech
      recognition scores (S/N: -5 to 15 dB) were 7 to 20% higher for the 3-channel AGC
      device compared to the single-channel AGC instruments. This finding is equivalent
      to an improvement of the S/N ratio of about 7 dB for the user. The results of the
      subjective judgements were similar for both subgroups. Sound quality and speech
      intelligibility were mostly rated as "very good" or "good" on a 5-point-scale.
      The subjects were also asked to compare the performance of their own hearing aids
      with the 3-channel AGC instrument; the latter generally turned out to be
      preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153568
TI  - 8-channel digital filter bank for hearing aid use: preliminary results in
      monaural, diotic and dichotic modes.
AB  - A digital 8-channel signal processing system has been implemented using a TMS
      320C25 signal processor. Tests with hearing-impaired subjects showed that the
      system allows a better fit to a specified frequency response than when using
      conventional aids with analog filtering. The filter bank has also been tested in
      dichotic listening experiments, where odd-number channels were fed to one ear and
      even-number channels to the other. The preliminary results on three hearing
      impaired subjects in repeated tests of speech recognition in noise showed an
      improvement in the order of 2 dB in speech-to-noise ratio for 50% correct
      recognition as compared to the complete broadband signal presented diotically.
      Temporal splitting of the signal by periodically switching of the odd and even
      bands between left and right ears did not show any improvement.

PMID- 8153567
TI  - Signal processing for hearing impairment.
AB  - Four noise reduction methods for use in sensory aids for hearing impairment were
      evaluated. These include a two-microphone adaptive noise canceller, short-term
      Wiener filtering, a transformed spectrum subtraction technique, and sinusoidal
      modelling. The largest improvements in speech recognition were obtained with the
      two-microphone adaptive noise canceller in a moderately reverberant room.
      Significant improvements were also obtained for short-term Wiener filtering for
      some hearing-impaired subjects. The transformed spectrum-subtraction technique
      failed to improve performance as the front-end of a hearing aid, but yielded
      improvements in performance as a preprocessor for the Nucleus Cochlear Implant.
      Sinusoidal modelling resulted in significant improvements in signal-to-noise
      ratio, but without a corresponding improvement in speech intelligibility.

PMID- 8153569
TI  - Effect on the speech reception threshold in noise of the recovery time of the
      compressor in the high-frequency channel of a two-channel aid.
AB  - This paper describes two experiments in a series evaluating and optimising a
      hearing aid incorporating two forms of automatic gain control (AGC). The first
      form is a front-end AGC which is normally slow acting and which compensates for
      variations in the overall level of speech from one situation to another. The
      second form of AGC follows the front-end AGC. The signal is split into two
      frequency bands, and fast-acting AGC is applied in the upper band only. The bands
      are then recombined. The two experiments described here were aimed at determining
      the optimum value of the recovery time of the AGC in the high-frequency channel.
      Speech reception thresholds (SRTs) were measured in the presence of speech-shaped
      noise as a function of the recovery time, for subjects with mild-to-moderate
      sensorineural loss. In the first experiment the recovery time was varied over the
      range 10-80 ms. SRTs tended to be lowest (best) at the shorter recovery times but
      the effects were small. In the second experiment, the recovery time was varied
      over the range 5-320 ms. In this case, there was a clear trend for SRTs to
      increase with increasing recovery time. A recovery time of about 20 ms appears to
      be optimal.

PMID- 8153570
TI  - Syllabic compression and speech intelligibility in hearing impaired listeners.
AB  - Syllabic compression has not been shown unequivocally to improve speech
      intelligibility in hearing-impaired listeners. This paper attempts to explain the
      poor results by introducing the concept of minimum overshoots. The concept was
      tested with a digital signal processor on hearing-impaired subjects. The results
      show that moderate syllabic compression may raise speech intelligibility, as long
      as overshoots are minimized and relatively short time constants are used.
      Frequency equalization also contributes to speech intelligibility.

PMID- 8153571
TI  - Longitudinal relationship between incisal tooth wear and periodontal condition.
AB  - The purpose of the study was to examine the relationship between the longitudinal
      development of incisal tooth wear and periodontal conditions in 51 persons. Stone
      casts obtained at the ages of 15 and 27 yr were used to assess incisal wear
      according to a graded scale, the Incisal wear Index (IwI). The wear increase
      after 12 yr, delta IwI, was related to the various health index scores at the age
      of 15 yr, including the Plaque Index (PlI) and Gingival Index (GI) systems. The
      chi-square tests showed a statistically significant association between delta IwI
      and periodontal condition in 15-yr-olds. Thus, relatively low PlI and GI values
      were accompanied by relatively high delta IwI values. It was concluded that in 15
      yr-olds, PlI and GI levels are clinical predictors of future wear (delta IwI) of
      maxillary and mandibular central incisors. Pocket depth (PD) was a less valuable
      clinical predictor of such wear.

PMID- 8153572
TI  - Differential periodontal temperature measurements in the assessment of
      periodontal disease activity: an experimental and clinical study.
AB  - The difference in surface temperatures between the bottom of periodontal pockets
      and the attached gingiva adjacent to the openings of the pockets were determined
      both in monkeys with experimental marginal periodontitis, and clinically in
      patients with marginal periodontitis. For this purpose a custom-made, temperature
      measuring device was developed which enabled immediate recording of temperature
      differences as well as periodontal pocket depths, bleeding, and attachment
      levels. The measurements were performed periodically. The differential
      temperature measurements were correlated to change in periodontal attachment over
      time. It was shown that differential periodontal temperatures are well correlated
      to change in periodontal attachment over time. It was furthermore concluded that
      differential periodontal temperature measurements have the potential of serving
      as a predictor of activity of marginal periodontitis. However, more extensive
      data are required to assess the sensitivity and specificity of the method.

PMID- 8153573
TI  - Short-term effect of topical application of delmopinol on salivary microbiology,
      plaque, and gingivitis.
AB  - The aim of this study was to test a possible dose-response effect of topical
      application of delmopinol HCl on the salivary microbiology, the healing of a pre
      established experimental gingivitis, plaque development, and supragingival plaque
      composition. Forty-eight healthy subjects were enrolled in an oral hygiene
      program for 2 wk to upgrade their oral health. After professional tooth cleaning,
      they abstained from all oral hygiene, but applied 2 ml of a placebo with a soft
      paintbrush onto their teeth twice daily for 2 wk. At the end of this period, the
      subjects received tooth cleaning and were then assigned to three treatment groups
      of 16 individuals each. They applied 2 ml of 0.1%, 0.5%, and 1% delmopinol HCl,
      respectively, twice daily for the next 2 wk and refrained from all other oral
      hygiene procedures. At the end of the placebo and delmopinol HCl treatment
      periods, (1) saliva samples were obtained and cultivated on a series of media,
      (2) the degree of gingivitis was measured with gingival crevicular fluid (GCF)
      and gingivitis index (GI), (3) the stainable buccal plaque extension was analyzed
      planimetrically, and (4) the bacterial morphotypes of plaque adjacent to the
      gingival margin were analyzed. No changes in the salivary microbiologic counts
      were detected. The amounts of GCF and GI were reduced in all delmopinol groups,
      as compared with placebo. Mean plaque extension was reduced by 16% for the 0.1%,
      56% for the 0.5%, and 58% for the 1% delmopinol group. Cocci appeared to
      predominate in bacterial dental plaque when 0.5% and 1% delmopinol were
      used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153574
TI  - Dental plaque inhibition by a combination of triclosan and polydimethylsiloxane
      (silicone oil).
AB  - It has previously been shown that a toothpaste which contains triclosan and
      polydimethylsiloxane (silicone oil) improved gingival health in a test panel with
      established gingivitis more markedly than usually observed when testing
      commercial triclosan-containing toothpastes. In the present study the mode of
      action of combinations of silicone oil and triclosan was investigated. An in
      vitro experiment showed that triclosan was retained in a thin layer of silicone
      oil on the inner surfaces of test tubes that had been treated with the
      combination of triclosan and silicone oil. This triclosan was slowly released and
      inhibited the growth of bacteria in the test tubes. Silicone oil alone and in
      combination with triclosan was able to inhibit polysaccharide adhesion to the
      test tubes in the presence of a strain of Streptococcus sobrinus and a sucrose
      containing medium. Corresponding in vivo experiments showed similar results;
      teeth topically treated with silicone oil and triclosan showed a marked plaque
      reduction, and those treated with silicone oil alone showed a moderate reduction,
      as compared with a placebo. The silicone oil plus 0.3% triclosan combination
      inhibited plaque formation also on proximal surfaces. It appears likely that this
      combination provides a reservoir of triclosan in the thin layer of silicone oil
      which binds strongly to teeth because of its low surface tension. Triclosan is
      then slowly released into saliva because of its low solubility in this fluid.

PMID- 8153575
TI  - Effect of fluoride on the rate of dentin apposition and caries progression in
      young and old Wistar rats.
AB  - The effect of fluoride in drinking water on the progression of dentinal caries
      and dentin apposition was studied separately in young and old Wistar rats. The
      animals were inoculated with Streptococcus sobrinus and fed ad libitum on a 43%
      sucrose diet and distilled water supplemented with 0, 1, or 19 ppm fluoride.
      After a 7-wk (young) or 13-wk (adult) cariogenic challenge, the areas of dentinal
      caries and dentin apposition were quantified after tetracycline staining.
      Fluoride in the drinking water reduced the progression of dentinal caries and the
      speed of dentin formation in the young animals but only the progression of dental
      caries in the adult ones. Both the progression of carious lesions in the dentin
      and the rate of dentin apposition were 10 times faster during primary
      dentinogenesis.

PMID- 8153576
TI  - Hg-provocation of oral mucosa in patients with oral lichenoid lesions.
AB  - Five amalgam-bearing patients, with clinically and histologically confirmed oral
      lichenoid lesions, were tested by applying 0.5% Hg in petrolatum for 10 min to
      clinically normal mucosa. Control sites were exposed to petrolatum only. Four
      amalgam-bearing patients with no clinical evidence of oral lichenoid lesions
      served as controls; they were subjected to similar Hg and petrolatum exposure.
      After 24 h, biopsies were taken and immunocytochemically analyzed with monoclonal
      antibodies to lymphoid and nonlymphoid cells. No distinct differences could be
      detected between the Hg-exposed areas of the lichen patients and those of the
      nonlichen patients. Furthermore, normal mucosa exposed to petrolatum only showed
      a staining pattern in the lichen patients which was no different from the
      nonlichen patients. The findings are discussed with respect to possible
      mechanisms of development of lichen-like lesions in oral mucosa.

PMID- 8153577
TI  - Description of persons with symptoms presumed to be caused by electricity or
      visual display units--oral aspects.
AB  - A questionnaire containing 20 questions was sent to 127 members of the
      Association for Those Injured by Electricity and Visual Display Units in northern
      Sweden, of whom 103 (81%) answered. The questionnaire consisted of questions
      about age, sex, and place of work. Furthermore, the members were asked to state:
      1) their general and oral symptoms; 2) whether they thought that dental amalgam
      and other types of dental filling materials had affected their symptoms; 3)
      whether they were replacing or had replaced their amalgam fillings and, if so,
      what effect it had had on their symptoms; 4) whether they had been medically
      examined; and 5) whether they were or had been sick-listed for their complaints.
      Of those who answered the questionnaire, 79% were women (mean age 45 yr) and 21%
      men (mean age 42 yr). Sixty percent worked in offices. In 82%, the symptoms had
      started at work. The mean duration of the symptoms was 5.2 yr. The symptoms were
      aggravated mostly in "electric environment in general" and in "office with
      computers". Skin complaints, fatigue, and eye symptoms were the most common
      general symptoms. Sixty-five percent mentioned that they had oral symptoms.
      Gustatory disturbances, burning mouth, and temporomandibular joint (TMJ)
      dysfunction were the most common oral symptoms. Fifty-six percent considered that
      dental amalgam and 24% that other dental materials affected the symptoms. Twenty
      one percent were in the process of replacing the amalgam fillings; 40% had
      already done so. After replacement, 37% had noticed a decrease of
      symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153578
TI  - Triclosan-containing mouthwashes--does the nature of the solvent influence their
      clinical effect?
AB  - The effect of triclosan on plaque inhibition was studied with various solvents.
      Eight subjects used the solutions as mouthwashes twice daily for 4 days while
      refraining from any other form of oral hygiene. Bacteriologic tests were also
      done with the same solutions. The study showed that the nature of the substance
      used to dissolve triclosan may be of clinical significance. Solutions of
      triclosan in polyethylene glycol, glycerol, or 3% sodium lauryl sulfate (SLS)
      alone showed marked antiplaque effect. (The first two solutions both contained
      1.5% SLS). However, triclosan dissolved in Tween 80 had only a negligible
      clinical effect. In vitro experiment showed that antibacterial tests did not
      correlate well with clinical data. It is proposed that the nature of the micelles
      of the detergents which are used to dissolve triclosan is of significant
      importance. Strongly charged micelles such as SLS show clinical effect, whereas
      less charged micelles of SLS/Tween 80 or uncharged micelles of Tween 80 alone
      appear not to have this effect.

PMID- 8153579
TI  - Similarities between Fusobacterium nucleatum and bacteroides fragilis studied by
      two DNA probes derived from Fusobacterium nucleatum.
AB  - A polymerase chain reaction (PCR)-amplified oligonucleotide DNA probe
      corresponding to a Fusobacterium nucleatum Fevl DNA region coding for a 40-kDa
      major outer-membrane protein (OMP) and a randomly cloned 2.1 kb DNA probe were
      found to recognize DNA from the Gram-negative bacteria Fusobacterium nucleatum
      and Bacteroides fragilis on Southern blots and slot blots. The results indicate
      sequence similarity within the DNA fragments studied. Immunoblots tested with
      polyclonal antibodies against whole cells of F. nucleatum revealed only weak
      antigen similarity between these species.

PMID- 8153580
TI  - Factors associated with salivary buffering capacity in young adults in Stockholm,
      Sweden.
AB  - The buffering capacity and flow rate of stimulated whole saliva were assessed in
      150 persons, 20-24 yr of age. The associations were assessed between the buffer
      value and the flow rate, some dietary factors, tobacco habits, use of oral
      contraceptives, and some demographic variables. The results demonstrate that a
      low flow rate may predict a low buffer value but not a high value. Flow rate
      accounted for the largest part of the buffering variation but morning and
      afternoon saliva sampling, female gender, food consumption between meals, and
      smoking seem to have contributed to low buffering values. Snuff-taking habits,
      oral contraceptives, and protein consumption between meals were not associated
      with the buffering capacity.

PMID- 8153581
TI  - Variation in torus palatinus prevalence in Norway.
AB  - The variation in torus palatinus (TP) prevalence was investigated among a total
      of 2010 dental patients over 10 yr of age native to two different regions in
      Norway, the Lofoten Islands in northern Norway and the Gudbrandsdalen valley, an
      inland area in the southeastern part of the country. The two groups were presumed
      to belong to the same Caucasian stock, but were extremes with regard to the fish
      to-meat ratio of the diet, which was 3:1 in Lofoten and 1:3 in Gudbrandsdalen,
      respectively representing a soft type of diet, and a tough type requiring greater
      muscular forces during mastication. The study revealed: 1) the prevalence of TP
      was higher among women than men; 2) TP seemed likely to arise from a
      multifactorial liability, with part of the genetic factors residing on the X
      chromosome; 3) the prevalence of TP appeared to be higher among natives of
      Lofoten, who consume the softer food, than among natives of Gudbrandsdalen, the
      higher prevalence being hypothesized to have some connection with nutrient
      substances present in saltwater fish, possibly omega 3 polyunsaturated fatty
      acids and vitamin D; and 4) TP seemed to be a dynamic phenomenon capable of
      growth and subject to resorption remodeling.

PMID- 8153582
TI  - Concurrence of torus mandibularis and torus palatinus.
AB  - Analysis of the concurrence of torus mandibularis and torus palatinus among a
      total of 2010 dental patients, by the test of independence, revealed that the
      concurrence was statistically significant among women, but not among men. A
      tentative hypothesis was proposed to explain the sexual dimorphism of the
      variable, combined occurrence of the two features.

PMID- 8153583
TI  - Mineral density in the mandibles of partially and totally edentate postmenopausal
      women.
AB  - Mineral density of the cortical bone in four regions and the spongiosa distal
      from the mental foramen of the mandible was determined by quantitative computed
      tomography (QCT) for 77 postmenopausal, 48-56-yr-old women. Of these women, 42
      were totally edentulous and 35 had teeth in region d35-d45. The bone mineral
      densities of different regions of these two groups were compared. Mineral density
      of the cortical bone on lingual and buccal sides, distal from the mental foramen,
      was significantly higher among those who had been edentate 12-23 yr than among
      dentate subjects. No differences were found between those who had been edentate
      less than 12 or over 23 yr and the dentate group. This study indicates that
      muscular activity during different phases of edentulousness regulates the density
      of bone in regions where muscles are attached.

PMID- 8153584
TI  - Pantomography in assessment of the osteoporosis risk group.
AB  - The diagnostic efficacies of three panoramic-based indices were compared with
      classification of bone mineral density by dual-energy x-ray absorptiometry. The
      panoramic indices were 1) cortical bone height, 2) an ordinal classification, and
      3) the Panoramic Mandibular Index. The results indicate that panoramic dental
      radiographs should not be used to assess the patient's status regarding
      osteoporosis, although the means of the variables in different mineral density
      groups of skeleton may differ significantly.

PMID- 8153585
TI  - Correlation between recordings obtained with a light-intensity tester and degree
      of conversion of a light-curing resin.
AB  - The present study evaluated the ability of a light-intensity tester (CL-Tester)
      to predict the degree of conversion of a resin. A light-curing resin was mixed
      from 25 mol-% BISGMA and 75 mol-% TEGDMA. The resin was cured with one of five
      different curing units whose light intensity varied from poor to very good when
      recorded with the CL-Tester. The degree of conversion was found by determination
      of the number of remaining double bonds (RDB) from transmission infrared spectra
      of the resin. The five mean values of RDB varied with statistical significance. A
      significant linear correlation was found between recordings of the CL-Tester and
      degree of conversion. It was concluded that the CL-Tester was able to predict the
      degree of conversion to such a degree that it may be expected to constitute a
      useful means of regular control of curing units.

PMID- 8153586
TI  - Autometallographic demonstration of mercury in rat molars.
AB  - Male, adult Wistar rats were exposed to 500 micrograms/m3 mercury vapor 6 h per
      day, 5 days a week for 4 wk. They were subsequently killed by transcardial
      perfusion. The molars were extracted, demineralized, and embedded in resin before
      sectioning. Autometallographic development was performed according to the method
      of Danscher & Moller-Madsen. Mercury deposits were found in small amounts in
      several areas of the pulp, but with larger accumulations of grains in relation to
      odontoblasts. Mercury also could be seen in odontoblastic processes in the dentin
      and predentin. Our conclusion is therefore that systemic uptake of mercury vapor
      leads to accumulation of mercury in the odontoblasts and that the mercury may be
      transported into the dentin tubules in the odontoblastic process.

PMID- 8153587
TI  - Cytogenetics and occupational exposures in acute nonlymphocytic leukemia and
      myelodysplastic syndrome. Working Group on the Epidemiology of
      Hematolymphopoietic Malignancies in Italy.
AB  - Studies on the association between cytogenetic aberrations and environmental or
      occupational exposures of patients with acute nonlymphocytic leukemia and
      myelodysplastic syndrome were selected from the literature and reviewed.
      Chromosome abnormalities as a whole and specific aberrations involving
      chromosomes 5, 7, 8, and 21 were considered. Occupational exposures were also
      considered as a whole or, whenever possible, as specific substances. An
      association between all occupations and any chromosome aberration has been
      observed in earlier studies but was not confirmed in later studies. Similar
      results have been observed when specific aberrations, or specific substances (ie,
      solvents) have been considered. Methodological issues and the comparability of
      the reviewed studies are discussed, and suggestions are made for refining
      epidemiologic investigations.

PMID- 8153588
TI  - Chromosome aberrations in chloralkali workers previously exposed to mercury
      vapor.
AB  - Chromosome aberrations and micronuclei in peripheral lymphocytes were studied in
      29 male chloralkali workers previously exposed to mercury vapor and in two
      matched reference groups comprising 29 nitrate fertilizer workers and 29 customs
      and police officers. The study was performed using whole-blood cultures with and
      without hydroxyurea and caffeine to inhibit deoxyribonucleic acid synthesis and
      repair, respectively. No significant differences in the frequencies of chromosome
      aberrations and micronuclei were observed. However, a nonsignificant increase in
      chromosome breaks and dicentrics was found in the subgroups with high urinary
      mercury peak levels or high cumulative mercury exposure. An increased prevalence
      of "high" scores of chromatid breaks in the inhibited cultures, exceeding the
      75th percentile of all of the subjects studied, was observed for the chloralkali
      workers when compared with both reference groups. No evident cytogenetic effects
      were observed among the chloralkali workers with the methods used in the present
      study.

PMID- 8153589
TI  - Cancer among farmers in central Italy.
AB  - This case-referent study evaluated cancer risks among farmers in central Italy.
      Cancer cases (N = 1674, 17 sites) were selected from all deceased men aged 35-80
      years; a random sample of 480 decedents formed the reference series. Farmers had
      a decreased risk of lung and bladder cancer and melanoma and nonsignificant
      excess risks for stomach, rectal, kidney, and nonmelanoma skin cancer. Stomach
      and kidney cancer were significantly increased among the farmers with > 10 years'
      experience, and stomach, rectal, and pancreatic cancer were increased among
      licensed pesticide users with > 10 years' experience. Possible relationships
      emerged between specific crops and cancer: fruit and colon and bladder cancer,
      wheat and prostate cancer, olives and kidney cancer, and potato and kidney
      cancer. The results regarding stomach, pancreatic, lung, bladder, and prostate
      cancer and melanoma congrue with earlier results. The kidney cancer excess, the
      association of colon and bladder cancer with orchard farming, and the excess of
      rectal cancer among licensed farmers are new and unexpected findings.

PMID- 8153590
TI  - Classification system for work in occupational health services.
AB  - Even though the World Health Organization has repeatedly advocated research on
      occupational health services to increase knowledge of its priorities and
      efficiency, no empirical study on work in such services is registered in major
      data bases. A common classification system for work in occupational health
      services is not available, but would facilitate comparison between studies. This
      report presents a feasible, reliable, and relevant classification for this
      purpose. Central among the policy-relevant questions on occupational health
      services is whether or not they work in accordance with their aims. Therefore,
      the project started from the aims of such services (in Norway and in the
      convention proposed by the International Labour Office in 1985) to obtain
      congruence between the instrument's eight categories of work and the aims of
      occupational health services. The classification was constructed in cooperation
      with occupational physicians and proved to be easy to use.

PMID- 8153591
TI  - Work content of Norwegian occupational physicians.
AB  - There is little empirical knowledge of the work done in occupational health
      services. In a study of the work of 50 Norwegian occupational physicians, their
      work on 249 workdays was recorded and classified into nine different categories
      according to the work content. Most (40%) of the work concerned work environment
      matters, 26% went to nonwork-related activities, 18% was for administration, 4%
      was for personal proficiency, and 12% went to various other activities. A total
      of 36% of the work concerned preventive activities, and 30% involved curative
      activities, of which two-thirds (22%) was for nonwork-related illnesses. This
      latter figure seems large in comparison with the preventive aims of occupational
      health services given by the Norwegian labor inspectorate. The physicians spent
      little time on educating employees about work environment matters and on new
      projects to ensure good work environment standards. The amount of activity
      involving occupational rehabilitation was fair.

PMID- 8153592
TI  - Multiple sclerosis and exposure to solvents, ionizing radiation and animals.
AB  - Earlier studies have indicated an association between multiple sclerosis and
      environmental factors, especially occupational exposure to solvents. The present
      study examined such relationships further. From medical files of hospitals in
      Kalmar and Jonkoping, 91 cases of multiple sclerosis, diagnosed in 1983-1988,
      were identified from population registers corresponding to the catchment areas of
      the hospitals, and 348 referents were randomly drawn. The cases and referents
      answered a questionnaire concerning occupational exposure and animal contacts.
      The men had significantly elevated risks, determined from logistic odds ratios,
      for solvent exposure, occupational contact with dogs or cats, and leisure-time
      contact with caged birds. X-ray treatment and previous diseases were risk
      indicators among the women. For the men and women together, solvent exposure,
      radiological work, and previous diseases were associated with clearly elevated
      risks. Although the study concerned rather few subjects, the findings indicate
      that several exogenous factors might contribute to the development of multiple
      sclerosis.

PMID- 8153593
TI  - Minor effects of low exposure to inorganic mercury on the human immune system.
AB  - The influence of exposure to inorganic mercury on the immune system was examined
      in 36 workers occupationally exposed to mercury vapor, 14 individuals with skin
      hypersensitivity to mercury compounds, 21 subjects with health disturbances
      allegedly caused by dental amalgam fillings ("amalgam disease"), and 39 healthy
      referents. Concentrations of mercury in blood and urine and some parameters
      judged to mirror different effects on the immune system were determined. The
      latter included, white blood cell differential counts, serum immunoglobulins and
      autoantibodies, and in vitro production of the cytokines interleukin 1 (IL-1) and
      tumor necrosis factor alpha (TNF alpha). Virtually all of the immunologic
      parameters were within normal ranges and did not differ significantly between the
      groups. In the group sensitized to mercury, there was a reduction of the in vitro
      production of both TNF alpha and IL-1 compared with the reference group's values.
      No significant correlations were noted between different mercury exposure
      estimates and the immunologic parameters.

PMID- 8153594
TI  - Effect of bright light on tolerance to night work.
AB  - Fifteen young (mean age 23.4 years) female nurses engaged in a resuscitation unit
      and working on a fast rotating shift schedule comprising two consecutive night
      shifts were exposed to short periods (4 x 20 min) of bright light (2350 lx)
      during their night duty to test a possible positive effect on their tolerance to
      night work. Two nights with normal lighting (20-380 lx) and two nights with
      bright light were compared. The following positive effects of bright light upon
      psychophysical conditions and performance efficiency were noted: in particular,
      signs of better physical fitness; less tiredness and sleepiness; a more balanced
      sleep pattern; and higher performance efficiency (letter cancellation test). This
      result could not be attributed to shifts of the internal clock although the exact
      cause remains to be determined. In fact, hormonal excretion and body temperature
      did not show any effect from bright light. In addition melatonin excretion was
      not suppressed appreciably by the bright light used.

PMID- 8153595
TI  - Microbial growth on respirator filters from improper storage.
AB  - Microbiological contamination and particle penetration were studied in two
      respirator filters with high efficiency. Microbial growth in filter materials
      during storage under conditions and the passing of microorganisms through the
      filters were particularly examined. Filters with different fiberglass and
      cellulose proportions were loaded in environments containing high microbial
      levels and incubated at a relative humidity of 98%. Particle penetration through
      loaded and incubated filters and carbon, nitrogen and microbial content were
      measured. After incubation, considerable particle penetration and the passing of
      fungal spores were observed for filters composed mainly of cellulose, probably
      because of humid conditions, which stimulated fungi to grow and extend mycelia
      and spores through the filter. Microbial activity, microorganism concentrations,
      and the chemical properties of the filter materials also supported this
      hypothesis. Storing used respirators in humid environments may result in heavy
      microbial contamination of the filters, especially if the filter material is
      biodegradable by microorganisms.

PMID- 8153596
TI  - Mortality update of cellulose fiber production workers.
AB  - Mortality ascertainment was extended through 1990 for a cohort of 1271 workers
      involved in the production of cellulose triacetate fiber at a plant in Rock Hill,
      South Carolina. Each subject was employed for at least three months between 1
      January 1954 and 1 January 1977 in jobs that entailed exposure to the highest
      concentrations of methylene chloride. Median exposures in 1977 ranged from 140 to
      745 ppm (8-h time-weighted average). The observed numbers of deaths from specific
      causes were compared with the expected numbers of deaths computed from rates in
      York County, South Carolina. For most causes of death, there was little if any
      association with employment. Among causes of particular interest, no new deaths
      were observed from cancer of the liver and biliary tract, although the excess
      from the earlier study persisted (4 observed, 1.34 expected). No excess mortality
      was observed for cancer of the pancreas (2 observed, 2.42 expected) or for
      ischemic heart disease (43 observed, 47.8 expected).

PMID- 8153597
TI  - Fatal cadmium-induced pneumonitis.
AB  - A previously relatively healthy 78-year-old man was exposed to cadmium fumes
      during brazing with cadmium-containing silver solder. He developed severe
      chemical pneumonitis and died 25 d after exposure.

PMID- 8153598
TI  - Re: "Urinary styrene in the biological monitoring of styrene exposure" by F
      Gobba, C Galassi, S Ghittori, M Imbriani, F Pugliese, A Cavaleri. Scand J Work
      Environ Health 1993; 19:175-82.

PMID- 8153599
TI  - [Functional dyspepsia. Old wine in new bottles?].
AB  - Functional dyspepsia covers various symptoms associated by the physician with the
      upper gastrointestinal tract without an identifiable organic cause. The existence
      of dyspepsia subgroups according to different symptom complexes, e.g. so-called
      "ulcer-like dyspepsia", has not been proved. Gastro-esophageal reflux disease is
      a distinguishable independent entity. Little is known about the pathogenesis of
      this common syndrome. Disturbances of gastric motility, especially postprandial
      antral hypomotility, are found in 50% of these patients but offer no explanation
      of the dyspeptic symptoms. Neither abnormal gastric acid secretion nor abnormal
      acid sensitivity has been proved in these patients. Furthermore, no relation
      between the symptoms and a Helicobacter pylori infection or a functional
      disturbance of the biliary tract has been established. In some cases fatty foods
      can provoke dyspeptic symptoms. Unfavorable psychosocial factors can influence
      the decision to consult a physician for dyspepsia. Recently, a lowered threshold
      of perception of stomach and small intestine distension in dyspepsia has been
      demonstrated. This disturbance of perception offers a new basis for further
      understanding and for possible treatment. Prokinetic agents can be of help in the
      treatment of functional dyspepsia. H2-receptor antagonists are most effective in
      patients presenting symptoms of gastro-esophageal reflux disease. Empiric
      therapeutic trials in this disease entity, which shows a high placebo response
      rate (between 30% and 60%), are not of proven value.

PMID- 8153600
TI  - [Esophageal thoracic pain: what can be done?].
AB  - At present, an esophageal origin can be identified in as many as 50% of patients
      with non cardiac chest pain. In about 1/3 of these patients, gastroesophageal
      reflux can be documented. In the remaining 2/3 of patients, various disorders of
      esophageal motility have been described. Abnormal esophageal motility may be
      classified as nutcracker esophagus, diffuse esophageal spasm, achalasia,
      hypertensive lower esophageal sphincter, and nonspecific esophageal motility
      disorders. Simultaneous recording of intraesophageal pH, pressure, and symptoms
      (combined 24-h pH-metry and manometry) makes it possible to test the temporal
      association between pain, reflux, or abnormal motility. This review describes the
      diagnostic evaluation and therapeutic options in patients with non cardiac chest
      pain. Identification of the esophageal origin of chest pain should improve the
      therapeutic results.

PMID- 8153601
TI  - [Acute ulcer disease: diagnosis, therapy, complications, indications for
      surgery].
AB  - The development of fiberoptic endoscopy, the creation of drugs with well
      understood mechanisms of action, and the definition of the role of Helicobacter
      pylori have resulted in a considerably better understanding of ulcer
      pathogenesis. This has led to rational concepts of ulcer therapy, which are
      discussed in detail in this review. Moreover, the role of non-steroidal
      antiinflammatory drugs in peptic ulcer disease, and the use of drugs and
      endoscopic measures in treatment of ulcer complications, especially g.i.
      hemorrhage, are discussed in detail. The implications of these advances with
      regard to the indications for surgical treatment of peptic ulcer disease are
      outlined.

PMID- 8153602
TI  - [Helicobacter and peptic ulcer: history, diagnosis and therapy--when, in whom and
      how?].
AB  - The pathogenesis of peptic ulcer disease is complex. It is associated with a
      spiral organism, Helicobacter pylori, which induces chronic gastritis. The
      evidence for a causal association between H. pylori and peptic ulcer disease
      stems primarily from the observation that eradication therapy with bismuth and
      various antibiotics may produce normalization of gastritis and possible cure of
      ulcer disease. The prevalence of H. pylori infection and potential implications
      for therapy are discussed. Who should undergo eradication therapy, and how? The
      problem remains that--despite the fact that a cure is possible--no simple therapy
      is available.

PMID- 8153603
TI  - [Structural factors influencing the horn quality and predilection sites for
      diseases at the bottom surface of the bovine hoof].
AB  - The quality of the horn of the cattle hoof varies in the different segments of
      the ground surface adapted to weight bearing. Horn quality is influenced by the
      following main factors: the keratin proteins as the most important intracellular
      factor, the intercellular cementing substance as the intercellular factor, and
      the architecture of the cluster of horn cells, i.e. the arrangement of horn cells
      in tubular and intertubular horn. Differences in the structure and composition of
      these factors and their respective combination determine the different degrees of
      hardness of hoof horn, which are even palpable. In special places, as i.e. the
      white zone, the combination of all these above-mentioned factors determines sites
      of predilection for diseases of the cattle hoof like white line disease.

PMID- 8153604
TI  - [Comparison of two ELISA systems for the detection of antibodies against IBR/IPV
      and against enzootic bovine leukemia virus].
AB  - Sensitivity and specificity of two ELISA systems for the detection of antibodies
      to Bovine Herpes-virus 1 (BHV1; IBR/IPV) were tested by using 214 sera of cattle
      with predetermined history of BHV1 infection and freedom from BHV1 infection,
      respectively. With these sera as "gold-standard", the sensitivity of ELISA1
      (HerdCheck: Anti-IBR) appeared to exceed 98%, whereas for ELISA2 (Checkit:
      Trachitest) a sensitivity of between 94 and 99.3% was determined. The specificity
      of ELISA1 amounted to at least 96.9%, whereas for ELISA2 it ranged apparently
      from 81.5 to 98.5%. When applied in routine testings of serum samples, the two
      ELISA systems correlated extremely well. With each test, only 3 of 1431 samples
      gave contradictory results. In all these cases, alternative tests suggested that
      the contradictions represented false-positive reactions. A similar correlation
      was observed when milk samples in the place of sera were probed. The serum and
      milk samples were additionally tested using two corresponding ELISA systems
      (obtained from the same manufacturers) for the detection of antibodies to Bovine
      Leukemia virus (BLV). The sensitivity and specificity of these tests could not be
      determined because of lack of samples with known history of infection. The
      results of the tests, however, correlated very well. Only 6 of 1431 sera reacted
      in a contradictory way. These observations indicate that the kits tested in this
      study, both for the detection of antibodies to BHV1 and to BLV, meet high quality
      standards. Possibilities to improve the kits were still detected.

PMID- 8153605
TI  - [Use in cats of the "small external fixator for hand and forearm" of the Study
      Group for Osteosynthesis Inquiries].
AB  - Results and experience of 38 applications of the small AO/ASIF external fixator
      in cats are reported. Problems, limits with this fixation system and possible
      further indications are discussed. In this study the external fixator proved to
      be a helpful supplement of stabilisation methods for treatment of fractures and
      luxations in cats. The external fixator was well tolerated by the cats in this
      study.

PMID- 8153606
TI  - [Pathology of cardiac ventricular aneurysms in the horse].
AB  - The authors describe pathologic and histopathologic findings of three cardiac
      aneurysms in horses, two of which in the left ventricle and one in the right
      ventricle. The aneurysms were always associated with multiple foci of myocardiac
      fibrosis. A hypothesis concerning histogenesis of the lesion is formulated.

PMID- 8153607
TI  - [Mycoplasma bovis. Spread of a new pathogenic agent in cattle in Switzerland?].

PMID- 8153608
TI  - [The revision of Article 65 Section 2 of the Animal Welfare Ordinance].

PMID- 8153609
TI  - The biological warfare of the future.

PMID- 8153610
TI  - Rising yen threatens key cancer study.

PMID- 8153611
TI  - Women in science. Disparities detailed in NCI division.

PMID- 8153612
TI  - Research grants. 'Secretary snafu' may cost researchers, universities.

PMID- 8153613
TI  - New tumor suppressor may rival p53.

PMID- 8153614
TI  - Anthropologists take the measure of humanity.

PMID- 8153616
TI  - Resistance to antibiotics.

PMID- 8153615
TI  - Reviving the antibiotic miracle?

PMID- 8153617
TI  - Funding crunch hobbles antibiotic resistance research.

PMID- 8153618
TI  - Resistance a European problem, too.

PMID- 8153619
TI  - Hungary sees an improvement in penicillin resistance.

PMID- 8153620
TI  - Search for sepsis drugs goes on despite past failures.

PMID- 8153621
TI  - Infectious disease surveillance: a crumbling foundation.

PMID- 8153622
TI  - Human mycoses: drugs and targets for emerging pathogens.

PMID- 8153623
TI  - Ubiquitous natural antibiotics.

PMID- 8153624
TI  - Inactivation of antibiotics and the dissemination of resistance genes.
AB  - The emergence of multidrug-resistant bacteria is a phenomenon of concern to the
      clinician and the pharmaceutical industry, as it is the major cause of failure in
      the treatment of infectious diseases. The most common mechanism of resistance in
      pathogenic bacteria to antibiotics of the aminoglycoside, beta-lactam
      (penicillins and cephalosporins), and chloramphenicol types involves the enzymic
      inactivation of the antibiotic by hydrolysis or by formation of inactive
      derivatives. Such resistance determinants most probably were acquired by
      pathogenic bacteria from a pool of resistance genes in other microbial genera,
      including antibiotic-producing organisms. The resistance gene sequences were
      subsequently integrated by site-specific recombination into several classes of
      naturally occurring gene expression cassettes (typically "integrons") and
      disseminated within the microbial population by a variety of gene transfer
      mechanisms. Although bacterial conjugation once was believed to be restricted in
      host range, it now appears that this mechanism of transfer permits genetic
      exchange between many different bacterial genera in nature.

PMID- 8153625
TI  - Prevention of drug access to bacterial targets: permeability barriers and active
      efflux.
AB  - Some species of bacteria have low-permeability membrane barriers and are thereby
      "intrinsically" resistant to many antibiotics; they are selected out in the
      multitude of antibiotics present in the hospital environment and thus cause many
      hospital-acquired infections. Some strains of originally antibiotic-susceptible
      species may also acquire resistance through decreases in the permeability of
      membrane barriers. Another mechanism for preventing access of drugs to targets is
      the membrane-associated energy-driven efflux, which plays a major role in drug
      resistance, especially in combination with the permeation barrier. Recent results
      indicate the existence of bacterial efflux systems of extremely broad substrate
      specificity, in many ways reminiscent of the multidrug resistance pump of
      mammalian cells. One such system seems to play a major role in the intrinsic
      resistance of Pseudomonas aeruginosa, a common opportunistic pathogen. As the
      pharmaceutical industry succeeds in producing agents that can overcome specific
      mechanisms of bacterial resistance, less specific resistance mechanisms such as
      permeability barriers and multidrug active efflux may become increasingly
      significant in the clinical setting.

PMID- 8153626
TI  - Resistance to antibiotics mediated by target alterations.
AB  - The development of resistance to antibiotics by reductions in the affinities of
      their enzymatic targets occurs most rapidly for antibiotics that inactivate a
      single target and that are not analogs of substrate. In these cases of resistance
      (for example, resistance to rifampicin), numerous single amino acid substitutions
      may provide large decreases in the affinity of the target for the antibiotic,
      leading to clinically significant levels of resistance. Resistance due to target
      alterations should occur much more slowly for those antibiotics (penicillin, for
      example) that inactivate multiple targets irreversibly by acting as close analogs
      of substrate. Resistance to penicillin because of target changes has emerged, by
      unexpected mechanisms, only in a limited number of species. However, inactivating
      enzymes commonly provide resistance to antibiotics that, like penicillin, are
      derived from natural products, although such enzymes have not been found for
      synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational
      design, rather than by the modification of a natural product.

PMID- 8153627
TI  - A mass spectrometric solution to the address problem of combinatorial libraries.
AB  - The molecular weights of femtomole quantities of small peptides attached to
      polystyrene beads have been determined with imaging time-of-flight secondary ion
      mass spectrometry. The analysis is made possible by the selective clipping of the
      bond linking the peptide to a bead with trifluoroacetic acid vapor before the
      secondary ion mass spectrometry assay. The approach can be applied to large
      numbers of 30- to 60-micrometer polystyrene beads for the direct characterization
      of massive combinatorial libraries.

PMID- 8153628
TI  - Adhesion forces between individual ligand-receptor pairs.
AB  - The adhesion force between the tip of an atomic force microscope cantilever
      derivatized with avidin and agarose beads functionalized with biotin,
      desthiobiotin, or iminobiotin was measured. Under conditions that allowed only a
      limited number of molecular pairs to interact, the force required to separate tip
      and bead was found to be quantized in integer multiples of 160 +/- 20 piconewtons
      for biotin and 85 +/- 15 piconewtons for iminobiotin. The measured force quanta
      are interpreted as the unbinding forces of individual molecular pairs.

PMID- 8153629
TI  - Structure of the Tet repressor-tetracycline complex and regulation of antibiotic
      resistance.
AB  - The most frequently occurring resistance of Gram-negative bacteria against
      tetracyclines is triggered by drug recognition of the Tet repressor. This causes
      dissociation of the repressor-operator DNA complex and enables expression of the
      resistance protein TetA, which is responsible for active efflux of tetracycline.
      The 2.5 angstrom resolution crystal structure of the homodimeric Tet repressor
      complexed with tetracycline-magnesium reveals detailed drug recognition. The
      orientation of the operator-binding helix-turn-helix motifs of the repressor is
      inverted in comparison with other DNA binding proteins. The repressor-drug
      complex is unable to interact with DNA because the separation of the DNA binding
      motifs is 5 angstroms wider than usually observed.

PMID- 8153630
TI  - Differential complementation of Bcr-Abl point mutants with c-Myc.
AB  - A complementation strategy was developed to define the signaling pathways
      activated by the Bcr-Abl tyrosine kinase. Transformation inactive point mutants
      of Bcr-Abl were tested for complementation with c-Myc. Single point mutations in
      the Src-homology 2 (SH2) domain, the major tyrosine autophosphorylation site of
      the kinase domain, and the Grb-2 binding site in the Bcr region impaired the
      transformation of fibroblasts by Bcr-Abl. Hyperexpression of c-Myc efficiently
      restored transformation activity only to the Bcr-Abl SH2 mutant. These data
      support a model in which Bcr-Abl activates at least two independent pathways for
      transformation. This strategy may be useful for discerning signaling pathways
      activated by other oncogenes.

PMID- 8153631
TI  - A dual embryonic origin for vertebrate mechanoreceptors.
AB  - Neuromasts, the mechanoreceptors of the lateral line system of fishes and aquatic
      amphibians, have previously been thought to develop exclusively from embryonic
      epidermal placodes. Use of fate mapping techniques shows that neuromasts of the
      head and body of zebrafish, Siamese fighting fish, and Xenopus are also derived
      from neural crest. Neural crest migrates away from the neural tube in developing
      vertebrates to form much of the peripheral nervous system, pigment cells, and
      skeletal elements of the head. The data presented here demonstrate that
      neuromasts are derived from both neural crest and epidermal placodes.

PMID- 8153632
TI  - Association of intestinal peptide transport with a protein related to the
      cadherin superfamily.
AB  - The first step in oral absorption of many medically important peptide-based drugs
      is mediated by an intestinal proton-dependent peptide transporter. This
      transporter facilitates the oral absorption of beta-lactam antibiotics and
      angiotensin-converting enzyme inhibitors from the intestine into enterocytes
      lining the luminal wall. A monoclonal antibody that blocked uptake of cephalexin
      was used to identify and clone a gene that encodes an approximately 92-kilodalton
      membrane protein that was associated with the acquisition of peptide transport
      activity by transport-deficient cells. The amino acid sequence deduced from the
      complementary DNA sequence of the cloned gene indicated that this transport
      associated protein shares several conserved structural elements with the cadherin
      superfamily of calcium-dependent, cell-cell adhesion proteins.

PMID- 8153633
TI  - Association of poly(CA).poly(TG) DNA fragments into four-stranded complexes bound
      by HMG1 and 2.
AB  - The tandemly repeated DNA sequence poly(CA).poly(TG) is found in tracts up to 60
      base pairs long, dispersed at thousands of sites throughout the genomes of
      eukaryotes. Double-stranded DNA fragments containing such sequences associated
      spontaneously with each other in vitro, in the absence of protein, forming stable
      four-stranded structures that were detected by gel electrophoresis and electron
      microscopy. These structures were recognized specifically by the nuclear
      nonhistone high mobility group (HMG) proteins 1 and 2 as evidenced by gel
      retardation. Such sequence-specific complexes might be involved in vivo in
      recombination or other processes requiring specific association of two double
      stranded DNA molecules.

PMID- 8153634
TI  - A cell cycle regulator potentially involved in genesis of many tumor types.
AB  - A putative tumor suppressor locus on the short arm of human chromosome 9 has been
      localized to a region of less than 40 kilobases by means of homozygous deletions
      in melanoma cell lines. This region contained a gene, Multiple Tumor Suppressor 1
      (MTS1), that encodes a previously identified inhibitor (p16) of cyclin-dependent
      kinase 4. MTS1 was homozygously deleted at high frequency in cell lines derived
      from tumors of lung, breast, brain, bone, skin, bladder, kidney, ovary, and
      lymphocyte. Melanoma cell lines that carried at least one copy of MTS1 frequently
      carried nonsense, missense, or frameshift mutations in the gene. These findings
      suggest that MTS1 mutations are involved in tumor formation in a wide range of
      tissues.

PMID- 8153635
TI  - [Bone healing after unreamed intramedullary nailing].
AB  - Good clinical results of unreamed nailing have been observed primarily in cases
      of open fracture. However, it is still unclear whether unreamed nailing is a
      suitable procedure for fractures that have previously been treated with reamed
      nailing. Since histological findings on bone healing after unreamed nailing were
      not available, an animal experiment on sheep was undertaken. The aim was to
      investigate whether there were differences in the nature of bone healing
      following reamed and unreamed nailing procedures. Fluorescence microscopy clearly
      showed that maximal callus formation occurred within 4 weeks after unreamed
      nailing and within 6 weeks after reamed nailing. Callus formation was also more
      prolific after unreamed than after reamed nailing. It was demonstrated by
      microradiography that bone regeneration progressed more rapidly, in terms of both
      periosteal and interfragmentary callus, after unreamed nailing. No disturbances
      of bone healing and no greater risk of pseudarthrosis were observed following
      unreamed nailing. Histological investigations showed that bone healing was faster
      after unreamed nailing and there was a reduced loss of vitality. This is of
      particular clinical relevance in the surgical treatment of fractures with severe
      soft tissue injury and of open and comminuted fractures. These results indicate
      that an extension of the indications for unreamed nailing should be considered.

PMID- 8153636
TI  - [Technique of plate osteosynthesis of the femur].
AB  - When plating is performed for fixation of complex femoral fractures the need for
      medial buttress to give durable weight-bearing ability of the bone is mandatory.
      However the means of achieving this is controversial. Many authors are in favour
      of mechanical reconstruction of the medial buttress, if necessary with a bone
      graft. Alternatively, medial buttress can be achieved by means of a technique
      allowing biological fracture healing, which is only possible, when the
      vascularity of all fragments is preserved. In 39 cases of osteosynthesis with
      plates for complex femoral fractures the bridging technique was used at surgery,
      to avoid denudation of the fragments. All osteosyntheses were performed without
      the application of bone clamps. After minimal exposure of the femur at the
      lateral side only, the plates were fixed in the main proximal fragment with one
      screw, in the case of blade plates the blade was fixed without bone clamps too.
      Afterwards the main distal fragment was drawn up to the plate and fixed directly
      and with a screw. In 9 cases the plates were inserted behind the vastus lateralis
      muscle, preserving its continuity, and fixed distally with another screw. After
      fine checking of the fracture alignment for rotation and length the plates were
      fixed with four or five screws in each main fragment, all at sites distant from
      the fracture. Meanwhile, all 39 fractures have consolidated. There were no cases
      of infection. Bone grafting was necessary in 8 cases. Only in 2 cases were the
      defects located in the medial area. In 37 of the 39 osteosyntheses an excellent
      medial buttress was achieved by bone healing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153637
TI  - [Animal experiment studies of "biological" plate osteosynthesis of multi-fragment
      fractures of the femur].
AB  - In three groups (A, B, C) of 12 sheep each, defined, reproducible comminuted
      subtrochanteric fractures were produced in three steps without devascularization
      of the bone: (1) longitudinal biocortical osteotomies limited by bore holes as
      breakpoints, (2) an external fixator producing a static lateral bending load of
      0.20 kN, (3) sudden three-point antero-posterior compression. Sheep in group A
      were treated with direct reduction and anatomical reconstruction of each fracture
      according to the principles of the AO/ASIF group and with an angle blade plate.
      In group B the same plate was used, but no attempt was made to reduce fragments
      anatomically. Length and alignment were restored with indirect reduction
      techniques (distraction via external fixator and articulating tension device)
      only. The treatment applied in group C incorporated the same reduction modes as
      that in group B, but an experimental plate with point bone contact and
      unicortical, fixed screws were used. After 4, 8 and 12 weeks of full weight
      bearing, the femurs were harvested for radiographic analysis and biomechanical
      testing. Subjective evaluation of fracture healing by 20 independent orthopaedic
      trauma surgeons resulted in significantly higher ratings for groups B and C than
      for group A after 8 (p = 0.07) and 12 weeks (p = 0.09). Density scan measurements
      showed little change in bone density as a percentage of that on the intact side
      over 12 weeks (108.1, 105.7, 104.4) in group A, but revealed marked changes in
      groups B and C (95.7, 117.5, 133.6 and 104.2, 125.6, 120.6), reflecting higher
      masses of callus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153638
TI  - [Distraction spondylodesis of the sacrum in "vertical shear lesions" of the
      pelvis].
AB  - The sacroiliac region is the link through which the weight of the trunk is
      transmitted to the legs and a region frequently indicated by patients as the site
      of back pain. Sacral fractures often remain undiagnosed and untreated and
      frequently result in neurologic symptoms and deficits. Since a systematic
      approach is used to analyse the pelvic ring fractures with CT scans, the surgical
      management of sacral fractures had become a focus of interest. Stabilization is
      important for survival of the patient and may improve the long-term functional
      results of treatment of such injuries. Specific treatments aimed at neurologic
      problems are available and may allow the patient functional recovery. Previous
      attempts to achieve internal fixation for sacral stabilization have used lag
      screws, sacral bars and plates in a compression mode. We present a new type of
      stabilization for vertically unstable sacral fractures in zones II and III
      (Denis). The aim of our suggested stabilization is a stable fixation without
      compression on the fracture side to protect the neural structures. We perform a
      transfixation from L5 to the pelvic rim with an internal fixator. Our
      instrumentation allows decompression (fracture reposition, sacral laminectomy,
      sacral foraminotomy) of the neural structures and stable fixation without
      compression. Five multiply traumatized patients with sacral fractures as a
      component of vertical shear injury of the pelvis had the sacroiliac region
      stabilized with the internal fixator. The preliminary results are presented.

PMID- 8153639
TI  - [Therapeutic procedure and long-term results in tibial pilon fracture in relation
      to primary soft tissue damage].
AB  - Between 1980 and 1990, 81 fractures of the pilon tibial of type B or C in the AO
      classification, presenting in 78 patients, were treated operatively in the
      Department of Traumatology and Emergency Surgery of the University Hospitals of
      Leuven. One-fourth of the fractures were open, 36 had second- or third-degree
      soft tissue damage according to the Tscherne classification system. The
      relationship between the fracture type and soft tissue damage was significant:
      the more severe the soft tissue damage, the more complex the fracture type. Screw
      osteosynthesis was performed mostly in fractures without soft tissue damage;
      plate osteosynthesis was used more frequently than external fixation in fractures
      with severe soft tissue damage. The number of late complications was much higher
      when the fracture was combined with severe soft tissue lesions. The number of
      secondary operative procedures on the soft tissue and bones was especially
      elevated in fractures primarily stabilized with a plate osteosynthesis. Sixty
      four patients were reviewed clinically and radiologically after a mean time of
      52.7 months. The subjective and objective end results were classified in
      accordance to the scales of Ovadia. Of the patients without soft tissue lesions,
      86.4% showed excellent or good subjective and 74.6% excellent or good objective
      end results; 55.6% of the patients with severe soft tissue damage had excellent
      or good subjective and 48.1% excellent or good objective end results. In pilon
      fractures with severe soft tissue damage, bony consolidation can only be reached
      after several operative steps. In the primary procedure, only minimal
      osteosynthesis, combined with medial external fixation should be
      performed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153640
TI  - [Value of computerized tomography in diagnosis of small intestine injuries after
      blunt abdominal trauma].
AB  - Intestinal injury is increasing in frequency among persons sustaining blunt
      abdominal trauma, and the consequences of delayed recognition of intestinal
      injuries are serious. This critical retrospective analysis evaluates the role for
      CT in the diagnosis of blunt abdominal trauma, including hollow visceral injury.
      CT scan, when used in conjunction with a history emphasizing the mechanism of
      injury and a careful physical examination, is highly accurate in detecting small
      bowel injuries. CT is less helpful in distinguishing between different types of
      small bowel injury. Intestinal wall thickening with low-density fluid in the
      abdominal cavity strongly suggests rupture. Until further experience is gained
      with CT, free intraperitoneal fluid in the absence of solid organ injury should
      be regarded as an indication for exploratory laparotomy.

PMID- 8153641
TI  - [Reconstruction of extensive post-traumatic femoral defects by autogenous rib
      transplants].
AB  - Extended deficiency pseudarthroses of the femur (7-18 cm) in nine patients were
      treated by autogenous rib transplantation. For early active pain-free
      mobilization we used the technique of bridging plate osteosynthesis for stable
      internal fixation. Within an average of 5 (range 4-7) months osseous restitution
      was obvious radiologically. In all nine patients the full weight-bearing capacity
      of the extremity was restored. There were no soft tissue problems and no bone
      transplant losses. All patients appreciated the uncomplicated postoperative phase
      after internal fixation with bridging plate osteosynthesis.

PMID- 8153642
TI  - [Long-term results of therapy of polytrauma patients with special reference to
      serial fractures of the lower extremity].
AB  - A random group of multiple traumatized patients (n = 50) was compared from the
      aspects of physical rehabilitation and social reintegration with a group of
      multiple traumatized patients (n = 54) all of whom had serial fracture of the
      lower extremity. In both groups automobile accidents were the main reason for the
      injury (in 62%). Motorcycle accidents were responsible in 29% of cases but
      resulted in twice as many extremity injuries as car accidents, in addition to
      which the treatment of patients with serial extremity injury lasted twice as long
      as that of those patients with only single extremity injury. In 40% of the first
      group more than two secondary hospital treatments were necessary. Two years after
      trauma working capacity was reduced by less than 20% in only 28.8% of patients
      with serial injuries as against 69.2% in the randomized group. Reduction of
      working capacity by more than 80% was observed in only 9% of patients in both
      groups. In these cases reduction of working capacity was mainly due to severe
      head injuries and not to limb fractures. Return to work was achieved only after
      retraining in most such cases, while in others a transfer within the same company
      made it possible. When patients were asked for their own opinions on the final
      results of treatment, 75% said they were satisfied. Our results underscore the
      importance of reestablishing normal function and of reintegration after extremity
      injuries but also the problems involved.

PMID- 8153643
TI  - [Current concepts in treatment of the unstable shoulder. Results of a countrywide
      survey].
AB  - The object of the study was to evaluate the management of patients with acute or
      recurrent shoulder instabilities. Therefore all trauma, general surgery, and
      orthopaedic departments in Germany were asked to complete a standardized
      evaluation form; completed questionnaires were returned from 880 institutions
      treating shoulder instabilities. Questions were asked about the diagnostic
      imaging techniques used and about conservative and operative treatment. In
      addition, the treatment regimens that would be followed for two typical patients
      were asked for. In patients with shoulder instabilities the following diagnostic
      imaging techniques were used: X-ray (97.1%), ultrasound (61.3%), CT (29.1%),
      arthro-CT (26.2%), MRI (13.3%), arthrography (24.1%), and arthroscopy (30.6%).
      After the first traumatic dislocation the average period of immobilization was
      2.2 weeks. Immobilization was achieved with a sling in 2.0%, with a Desault
      bandage in 38.8%, with a Gilchrist bandage in 72.7%, and with a cast in 4.2% of
      cases. Open surgical stabilization was performed according to Bankart (30%), Eden
      Hybinette (28.6%), Weber (Osteotomy) (27.1%), Lange (15.5%), Putti-Platt (13.6%),
      and other procedures (Magnusson-Stack, Bristow) only occasionally. The average
      period of immobilization after open surgery was 3.0 weeks. Arthroscopic
      stabilization techniques were applied by 7.5%. In a 19-year-old handball player
      stabilization would be performed immediately after the first traumatic
      dislocation in 9.2% of the institutions; in 34.4% the patient would not be
      operated on, and in 56.3% the shoulder would be stabilized after the third
      redislocation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153644
TI  - [Arthroscopic subacromial decompression--indications in os acromiale?].
AB  - A total of 122 patients with subacromial pathology without tears in the rotator
      cuff underwent arthroscopic subacromial decompression (ASD) and were re-examined
      1-3 years after the operation. All patients' data were recorded before and after
      operation with reference to a 100-point shoulder score. The group included 12
      patients who proved to have an os acromiale on X-ray. Postoperatively scores wee
      significantly higher (p < 0.05). Patients with os acromiale had a slightly but
      not significantly worse outcome than the others. Results were excellent in 43% of
      all patients, good in 17%, and fair in 25%, while 15% were considered failures.
      Again patients with an os acromiale had a slightly, but not significantly, worse
      result. Patients with a preoperative pain history of more than 1 year had a
      significantly worse result than those with a preoperative course of less than 1
      year (p < 0.05). This was true for both groups without any differences between
      them. Older patients also scored worse in both groups. Other factors, e.g. sex,
      preoperative range of motion, and muscle atrophy, did not significantly influence
      the result. Our results after ASD in patients with subacromial pathology without
      rupture of the rotator cuff and with os acromiale are encouraging. Therefore,
      this minimally invasive procedure seems to be a reasonable alternative to other
      complex procedures with ORIF in selected cases.

PMID- 8153645
TI  - [Distal diaphyseal fracture of the humerus].
AB  - Fractures of the distal humeral diaphysis are rare and have not been reported
      very often in the literature, although therapeutic management is more difficult
      than that of midshaft humeral fractures. As they are so near to the elbow, these
      fractures are not suitable for bracing, because pro/supination movements cannot
      be eliminated. Muscular forces, especially of the pronator teres muscle, force
      the fracture into a varus position with every supination movement. From 1974 to
      1990 we treated 174 fractures of the humeral diaphysis by operative means; 31 of
      these were located in the distal third. According to the AO classification, 8
      were graded as less difficult type A fractures, 15 as type B and 7 as type C
      fractures. In 22.6% of the patients primary radial palsy was present. In all, 15
      fractures were treated by plating, 9 with Hackethal's bundle nails and 6 with
      monolateral fixators. These last patients had sustained either multiple trauma or
      severe soft tissue injury or both. The plated cases included 1 with non-union and
      with superficial infection, both in type C comminuted fractures. In 1 case the
      fracture was not suitable for plating, and in the other case technical errors led
      to failure. In the 9 cases treated with Hackethal nails there were no
      complications. The advantage of the method is that the nails are inserted far
      distant from the fracture site. Anatomical reduction is not necessary, which
      means there is no danger of devitalizing fragments; the technique is also quick.
      In the "fixator" group, we saw 1 case of non-union and 1 of refracture, both
      following compound fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153646
TI  - [The "biological" plate osteosynthesis in multi-fragment fractures of the para
      articular femur. A prospective study].
AB  - In a prospective study, 24 fractures of the femur were treated by indirect
      reduction and internal fixation with a condylar plate or a condylar buttress
      plate. The inclusion criterion was that each patients's fracture(s) should be
      amenable to indirect reduction. The goal of the study was to determine the value
      of biological plating techniques incorporating the use of the distractor and the
      articulating tension device for indirect reduction, bridging of the fracture zone
      without dissection of the medial cortex, and calculated instability through
      undetermined axial compression. Most fractures were comminuted (5 type A, 10 type
      B and 9 type C according to the AO classification); 14 fractures were
      subtrochanteric, 8 fractures were supra-/intracondylar and 2 were diaphyseal in
      nature. The average age of the 14 mean and 10 women was 46 years (16-96). In 4
      cases the fracture was open; 8 patients had multiple trauma and 6 had further
      ipsilateral fractures. The fractures were sustained in motor vehicle accidents in
      14 cases. In 16 fractures operative treatment was performed within 36 h. All
      fractures were reduced indirectly, and 21 fractures were put under axial
      compression. There was no medial cortex dissection and no primary bone grafting.
      Secondary bone grafting was necessary in 2 patients, while 1 (diaphyseal
      fracture) had delayed bone union and required interlocking nailing. In 2 patients
      varus deformities under 10 degrees were present after completion of bone healing.
      There were no refractures and no implant failures. Full weight-bearing commenced
      at 14.7 weeks. Bone healing time was 18.7 weeks in the 19 patients followed
      up.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153647
TI  - [Baker's cysts. A follow-up study after surgical therapy].
AB  - Baker's cysts have to be regarded as a secondary phenomenon of knee-joint
      diseases. In the treatment of Baker's cysts, therefore, arthroscopy should be
      done before extirpation. In our study we wanted to look at the results of this
      therapeutic concept. In the surgical clinic within the Ruhr University of Bochum
      34 patients with Baker's cysts underwent an operation between 1985 and 1992. In
      22 patients the main symptom was swelling in the hollow of the knee, while the
      others reported effusions of the knee joint, pain or restricted joint movement.
      In 27 cases the diagnosis was made by ultrasound alone; in the others
      arthrography or NMR tomography was necessary. Arthroscopy was performed in all
      patients, revealing lesions of the meniscus in 12 cases, rupture of the cruciate
      ligament in 1, degenerative changes in 15 and chronic polyarthritis in 1. In 5
      patients we could not find any pathologic changes. We observed 1 severe
      postoperative complication in the form of a joint infection. Histological
      examination of the cysts showed chronic synovialitis in 21 patients and
      tuberculous arthritis in 1. In 25 of our patients clinical and ultrasound
      examination were then performed on average of 34 months after their operations.
      In 4 patients we found recurrence of cysts: 2 of these patients were found to be
      suffering from chronic knee-joint disease with effusions; 1 had recurrent
      hydrarthrosis together with chronic renal insufficiency; and the fourth patient
      had constant knee pain, though the arthroscopy did not show any pathologic
      changes. In the last case our diagnosis was therefore called in
      question.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153648
TI  - [Spontaneous "regeneration" of the spinal canal in traumatic bone fragments after
      fractures of the thoraco-lumbar transition and the lumbar spine].
AB  - This is a report about four patients in whom spontaneous remodelling of the
      spinal canal was observed after thoracolumbar fractures with intraspinal bone
      fragments leading to narrowing by 33-93%. One of the patients was female and
      three male; two patients had partial neurologic deficits and two had none. The
      ages of the patients were 33, 16, 65 and 16 years, and the fractures were
      localized in one case in segment T-12 in two in L-1 and in one in L-4. Active
      functional treatment was performed with no repositioning or plastering. The
      changes in spinal canal narrowing and the bone union were monitored by means of
      CT scans. The follow-up is 9-27 months. The intraspinal bone fragments gradually
      disappeared in all cases, while the partial neurologic deficits regressed. All
      patients are now free of troublesome complaints. We would therefore like to point
      out that thoracolumbar fractures without complete neurologic deficit that are
      associated with intraspinal bone fragments, whatever their size, should not
      immediately be treated by surgery, because conservative active functional
      treatment with spontaneous remodelling of the spinal canal gives results as good
      as those of operative treatment with far less risk.

PMID- 8153649
TI  - [Standardized analysis of acetabulum cup migration in hip endoprosthesis using
      digital image processing].
AB  - Measurement of the migration of the acetabular component following total hip
      replacement seems to be a useful method of early detection of aseptic loosening.
      The methods used so far for migration analysis are either too time-consuming or
      too elaborate in terms of the technical equipment required, and are therefore not
      suitable for use in day-to-day clinical practice. Analysis software based on the
      methods described by Nunn and Sutherland was developed with the aid of digitized
      conventional radiographs of the pelvis. It allows a planar migration measurement
      including cup inclination following manual marking of only five reference points
      on a computer screen. A correction for projection enlargement and rotational
      malpositioning of the patient is performed. All results are stored in a data bank
      and automatically compared with those recorded at previous follow-ups. Five
      different acetabular cups were analysed by a conventional and by a digital method
      for calculation of intra-observer variability. The standard deviation (SD) for
      horizontal and vertical migration was 0.2-0.4 mm and that for inclination angle
      0.8-1.4 degrees with digital evaluation. For manual measurement the SD was 0.4
      0.8 mm for migration and 0.8-1.2 degrees for inclination. A pelvis phantom was
      measured in nine different positions (neutral, 5 degrees and 10 degrees cranial
      and caudal inclination, 5 degrees and 10 degrees rotation to each side). Four
      different acetabular cup design were examined, each of which yielded a series of
      nine measurements. Within these series the SD for biplanar distances varied
      between 0.1 mm and 1.2 mm and for inclination between 1.1 degree and 2.3 degrees.
      Intra-observer variability was negligible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153650
TI  - [A new procedure for determination of leg length and differences in leg length
      using sonography. I. Development and experimental studies].
AB  - The precise measurement of leg length and leg length discrepancies (LLD) plays an
      important role in the examination of lumbar spine and lower extremities. Those
      real LLD which may be posttraumatic or idiopathic, can sometimes hardly be
      differentiated from LLD caused by spinal scoliosis or malposition. Although there
      is no final agreement, to which extent a LLD becomes clinically significant, most
      authors state that clinical assessment of LLD by tape measure or lengthening of
      the short leg with blocks of known thickness is highly unreliable. Radiological
      methods are necessary for precise detection of LLD less than 10 mm. Since
      previously reported non-invasive, ultrasound-supported leg-length measurement
      methods proved to be complicated and unhandy, a new method was developed. To
      avoid radiation exposure accuracy and precision were tested on human cadavers and
      were compared to clinical assessments by tape measurement. A measurement device
      was constructed consisting of a wire rope meter and a length millimeter digital
      display. Measurements were taken with the examined person in supine position. The
      device was placed beyond their feet and the end of the rope was hinged with a
      metal brace to a convenient transducer in exact middle position. Thus the middle
      of the ultrasound monitor concords with the end of the rope. The medial knee
      joint and ventral hip joint were used as standardised sonographic landmarks. Ten
      not pre-selected mortants were measured in this manner and additionally clinical
      LLD was obtained with a tape measure (medial ankle to anterior superior iliac
      spine). Afterwards all distances were anatomically prepared and measured with a
      meter stick.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153651
TI  - Dose-intensive chemotherapy with cytokine support.

PMID- 8153652
TI  - Evaluation of the importance and relevance of dose intensity using epirubicin and
      cyclophosphamide in metastatic breast cancer: interim analysis of a prospective
      randomized trial.

PMID- 8153653
TI  - High-dose intensity regimens with epirubicin in ovarian cancer.

PMID- 8153654
TI  - High-dose chemotherapy with autologous bone marrow transplantation for the
      treatment of malignant ovarian tumors.

PMID- 8153655
TI  - High-dose or dose-intensive chemotherapy for non-small cell carcinoma of the
      lung.

PMID- 8153656
TI  - Advances in chemotherapy for small cell lung cancer.

PMID- 8153657
TI  - Escalating high-dose epirubicin plus cisplatin in small cell lung cancer with
      granulocyte-macrophage colony-stimulating factor use when appropriate.

PMID- 8153658
TI  - Efficacy of intensive, high-dose anthracycline-based therapy in intermediate- and
      high-grade non-Hodgkin's lymphomas.

PMID- 8153659
TI  - Neuropathology of malignant gliomas.
AB  - Astrocytomas are the most common primary gliomas, with the highly anaplastic
      glioblastoma multiforme being the most frequently occurring astrocytoma.
      Distinctive histological features permit astrocytomas to be graded into levels of
      anaplasia, and these histological grades correlate with biological behavior and
      patient prognosis. However, there is also a strong correlation between patient
      age, tumor grade, and prognosis. More objective indicators of tumor proliferative
      potential, such as BUdR or Ki-67 LI, are currently being investigated with the
      hope that these will be a more accurate means of predicting patient survival.
      Oligodendrogliomas are a much less common primary glioma, with a generally better
      survival rate than astrocytomas. However, grading systems for oligodendrogliomas
      are not well defined. For any type of glioma, subsequent surgery after radiation
      therapy may be required for treatment of therapeutic effects or for therapy
      planning at recurrence. The histological changes observed in these post-therapy
      biopsy specimens or resections may be difficult to distinguish from reactive
      changes that can simulate recurrent tumor and vice versa.

PMID- 8153660
TI  - The molecular biology and molecular genetics of astrocytic neoplasms.

PMID- 8153661
TI  - Immunobiology of malignant astrocytomas.

PMID- 8153662
TI  - Imaging of gliomas.

PMID- 8153663
TI  - Malignant astrocytomas: surgical aspects.

PMID- 8153664
TI  - Brachytherapy and hyperthermia for malignant astrocytomas.

PMID- 8153665
TI  - Contemporary approaches to the treatment of malignant gliomas with radiation
      therapy.

PMID- 8153666
TI  - The chemotherapy of high-grade astrocytomas.

PMID- 8153667
TI  - Low-grade gliomas, mixed gliomas, and oligodendrogliomas.

PMID- 8153668
TI  - Immunotherapy of malignant gliomas.

PMID- 8153669
TI  - Pediatric glial neoplasms including brain-stem gliomas.

PMID- 8153670
TI  - Quality-of-life issues in patients with malignant gliomas.

PMID- 8153671
TI  - Recombinant human erythropoietin for the treatment of anemia in patients with
      advanced cancer.
AB  - The results of the multicenter trials demonstrate that r-HuEPO therapy can
      increase the hematocrits of anemic patients with advanced cancer. The multicenter
      trials were undertaken because, in previous smaller trials without placebo
      controls, patients with cancer and anemia had been shown to be likely responders
      to r-HuEPO therapy. To varying degrees in these trials, RBC transfusion
      requirements were eliminated or decreased in comparison to those of placebo
      treated patients, and anemia was lessened or corrected in the r-HuEPO groups. The
      side effects of r-HuEPO treatment were minor; anemic patients with advanced
      cancer receiving r-HuEPO therapy did not develop significant hypertension,
      seizures, or thrombotic events, and progression of tumor was not observed.
      Moreover, patients in the multicenter trials whose hematocrits increased to 38%
      or greater, or increased 6 percentage points or more, experienced significant
      improvement in all aspects of the quality of their lives. On the basis of these
      trials, r-HuEPO therapy appears to treat effectively the anemia of cancer. The
      importance of eliminating the need for transfusions and preventing sensitization
      to human leukocyte antigens will be major factors affecting the clinical future
      of r-HuEPO.

PMID- 8153672
TI  - Recombinant human erythropoietin enhances blood donation for autologous use and
      reduces exposure to homologous blood during elective surgery.

PMID- 8153673
TI  - The clinical physiology of erythropoietin.
AB  - From the foregoing data, it is clear that erythropoietin production is tightly
      regulated not only under normal circumstances but also during hypoxia, unless the
      hypoxia is extreme. Various disease states can have a negative impact on
      erythropoietin production, but while altering it quantitatively, they do not
      appear to abrogate basic fundamental control mechanisms. Rather, the threshold
      stimulus for either the recruitment of cells to produce erythropoietin or the
      effective production of erythropoietin is altered, usually in a predictable
      fashion. However, a reduction in erythropoietin production inevitably leads to a
      reduction in erythropoiesis. Nevertheless, assuming that the bone marrow remains
      responsive, administration of exogenous erythropoietin will increase the red
      blood cell mass. The immunoassay for serum erythropoietin therefore provides a
      means for identifying those situations in which erythropoietin therapy should be
      effective, but the assay must be used critically, bearing in mind the physiology
      of the hormone and the threshold concept of erythropoietin production (Table 3).

PMID- 8153674
TI  - Use of recombinant human erythropoietin to treat the anemia of myelodysplastic
      syndromes.

PMID- 8153675
TI  - Treatment of the anemia of multiple myeloma: the role of recombinant human
      erythropoietin.
AB  - Patients with relatively higher endogenous EPO levels (> 100 U/L) in the Arkansas
      study showed late responses or failed to respond, analogous to earlier
      observations by Ludwig et al, as well as by Fischl et al, and colleagues, who
      studied r-HuEPO administration in acquired immunodeficiency syndrome patients
      receiving r-HuEPO for anemia associated with zidovudine therapy. Thus, r-HuEPO
      substitution therapy is more likely to benefit patients whose anemia is
      associated with inappropriately low EPO serum levels. Granulopoiesis and
      thrombopoiesis were unaffected, and multiple myeloma cell stimulation has not
      been observed. The relative lack of toxicity from subcutaneously administered r
      HuEPO at a dose of 150 U/kg three times weekly makes this approach an effective
      adjunct in the management of patients with multiple myeloma, especially those
      unresponsive to chemotherapy and remaining symptomatic from their anemia.

PMID- 8153676
TI  - Fever of unknown origin.

PMID- 8153677
TI  - Juvenile myoclonic epilepsy.

PMID- 8153678
TI  - Juvenile myoclonic epilepsy--a report of 11 patients at the University Hospital,
      Kuala Lumpur.
AB  - This is a report on 11 cases of Juvenile Myoclonic Epilepsy (JME) from the
      University Hospital, Kuala Lumpur, all of whom were diagnosed in the last one and
      a half years. This genetic syndrome is seen in all the three main racial groups:
      Chinese, Malays and Indians. It accounts for 2% of the epilepsy patients seen at
      the neurology clinic. Lack of awareness is the main hindrance to diagnosis.

PMID- 8153679
TI  - Diabetic ketoacidosis--a study of 33 episodes.
AB  - Twenty-six patients presenting with 33 episodes of Diabetic Ketoacidosis (DKA)
      and managed on a protocol oriented system were analysed. Diabetes mellitus was
      newly diagnosed at presentation in 18% of the 33 episodes. The presenting
      symptoms were polyuria and polydipsia (58%), nausea and vomiting (52%), change in
      sensorium (24%), hyperventilation (24%), and abdominal pain (18%). The main
      clinical findings at admission were dehydration (97%), acidotic respiration
      (67%), coma and confusion (61%), a clinically detectable source of sepsis (49%),
      fever (33%) and hypotension (9%). Blood sugar levels at admission ranged between
      351 mg/dl and 1200 mg/dl (mean = 633 mg/dl). The mean serum potassium at
      diagnosis was 5.1 mmol/l and the mean calculated serum osmolality was 320
      mOsm/kg. The mean serum osmolality was higher in those with disturbed conscious
      level. Infections, particularly those of the urogenital tract, were the main
      precipitating cause for the DKA. Only 12 of the 19 patients with sepsis had
      fever. Eight of the episodes were attributed to patients' non-compliance with
      insulin. Four patients died during the 33 hospitalisations, giving a mortality
      rate of 10%. Death occurred despite glucose control and stabilisation of the
      ketoacidotic state and was due to uncontrolled septicaemia. The mean duration of
      hospitalisation was 11 days. The ketoacidosis state was reversed after a mean
      duration of 9.5 hours, with an average soluble insulin requirement per patient of
      52.4 units.

PMID- 8153680
TI  - Factors influencing pulse oximetry as compared to functional arterial saturation
      in multi-ethnic Singapore.
AB  - Noninvasive oximetry provides continuous monitoring of arterial oxygen saturation
      and hence, early detection of hypoxia. This has proved to be a useful adjunct to
      patients' safety, and is considered indispensable in certain settings. However,
      errors may be present in the pulse oximeter estimation (SpO2) of arterial oxygen
      saturation (SaO2), which may be due to various parameters. We have studied a
      multi-ethnic population where the skin pigmentation is different, and also under
      different conditions comparing SpO2 with SaO2. Our results showed that SpO2
      estimation of SaO2 amongst the three racial groups (Chinese, Malays, and Indians)
      varied significantly (ANOVA, p < 0.05). The over-estimation was more pronounced
      by hypoxic conditions and jaundice. Haemoglobin and systolic blood pressure did
      not affect the difference between SpO2 and SaO2.

PMID- 8153681
TI  - Three year results of radial keratotomy surgery at the National University
      Hospital, Singapore.
AB  - This paper presents the three year results of radial keratotomy (RK) surgery on
      51 of the first 59 consecutive eyes at the National University Hospital in
      Singapore. Before surgery, uncorrected visual acuity was worse than 6/24 in all
      eyes with 33.3% worse than 6/60. The average pre-operative spherical equivalent
      (SE) was -4.56 Dioptres(D). Three years after surgery the mean SE was -0.66D, a
      change of 3.9D; and 72.5% of eyes were within 1D of emmetropia. 70.6% had
      uncorrected visual acuity of at least 6/12 with no eyes having worse than 6/60
      visual acuity. Analysis based on levels of pre-operative myopia showed that the
      best visual and refractive results were obtained in patients with SE of -6D or
      less. None of the patients were troubled by complications such as glare,
      fluctuating vision, irritation and discomfort three years after surgery. Our
      results indicate that RK surgery is safe and effective through the three years
      and more following surgery.

PMID- 8153682
TI  - The use of fine needle aspiration biopsy in patients with multiple
      lymphadenopathy before open biopsy.
AB  - When a clinician is faced with a patient who presents with lymphadenopathy and in
      whom the clinical examination and routine investigations are normal, excision
      biopsy is usually the next step of management to obtain a tissue diagnosis. In a
      patient who has multiple lymphadenopathy, deciding on which node to biopsy can be
      difficult because some of the enlarged nodes may not reflect the true disease
      process. When such a lymph node is biopsied, the actual diagnosis can be delayed
      or even missed. Fine needle aspiration biopsy has been shown to be an effective
      tool in the investigation of multiple lymphadenopathy. Many, if not all, of the
      enlarged lymph nodes can be sampled at one sitting. If this procedure fails to
      provide a definitive diagnosis, the clinician should then proceed on to an open
      biopsy. Two cases of multiple lymphadenopathy in which open biopsies failed to
      reveal the true nature of the disease but subsequent fine needle aspiration
      biopsies did are presented and discussed.

PMID- 8153683
TI  - General anaesthesia vs sedation for minor gynaecological procedures--a
      comparative study.
AB  - Sedation using combined intravenous midazolam and fentanyl is a popular technique
      for minor gynaecological procedures. However, it is fraught with inconsistency in
      efficacy and has a greater tendency to perioperative oxygen desaturation. Fifty
      female ASA I patients scheduled for minor gynaecological procedures were given
      intravenous midazolam and fentanyl before surgery started. Intraoperative
      excessive movement that interfered with surgery and failure to maintain a patient
      airway were noted. Perioperative oxygen saturation was monitored with the pulse
      oximeter. In another group of 50 female ASA I patients, intravenous thiopentone
      was given and anaesthesia maintained with 67% nitrous oxide in 33% oxygen and
      0.5% of isoflurane via a face mask. Results showed that 10% of the sedated
      patients had excessive movements that interfered with surgery, of which 6% needed
      a general anaesthetic. Twenty-two percent of the sedated patients needed
      maintenance of airway perioperatively. Perioperative oxygen desaturation was
      profound in incidence and degree in the sedated patients whereas no patient who
      received general anaesthesia desaturated. The perioperative incidence of
      desaturation in the sedated patients was 46%. Intraoperatively, 28% (p < 0.001)
      of the sedated patients had oxygen saturation in the range of 85 to 90% and 18%
      of them (p < 0.01) had oxygen saturation of less than 85%. Postoperatively 8% of
      the sedated patients had oxygen saturation of 85 to 90%. We conclude that general
      anaesthesia is more efficacious and safer than sedation in patients scheduled for
      minor gynaecological procedures. The same minimum standard of monitoring applied
      to general anaesthesia should be used for sedated patients.

PMID- 8153684
TI  - First admission schizophrenia: clinical manifestation and subtypes.
AB  - This paper describes the clinical manifestations and classification of
      schizophrenia in Singapore. The subjects were all first admission to Woodbridge
      Hospital in 1975. They were followed up 5, 10 and 15 years later. There were 423
      patients. Of these, 17% had no delusions or hallucinations and 14% presented with
      only negative and withdrawn behaviour. They can be subdivided into four subtypes:
      paranoid, hebephrenic, "catatonic" and simple. Follow-up study showed that the
      percentage of full, partial and no recovery remained the same at around 30%, 30%
      and 40% at the end of 5, 10 or 15 years. The paranoid subtypes had best outcome
      and the simple had the worst outcome. Bleuler's criteria and his subtypes of
      schizophrenia are accepted by most psychiatric textbooks. These criteria did not
      include behavioural disturbances which are the commonest manifestations in this
      study. Other follow-up studies confirmed that paranoid patients have the best
      long-term outcome.

PMID- 8153685
TI  - Mammography and screening for breast cancer.
AB  - Mammography has been in general use as a breast imaging procedure for many years.
      More recently, it has taken on another important role, as a screening procedure
      for breast cancer. This article reviews its effectiveness in reducing morbidity
      and mortality resulting from the disease.

PMID- 8153686
TI  - Infections in systemic lupus erythematosus.
AB  - A prospective study was carried out on the occurrence of infections in 28
      hospitalised systemic lupus erythematosus (SLE) patients. In 38 episodes of
      infections, 23 were bacterial (60.5%), 4 were viral (10.6%) and culture negative
      infections were present in 10 (26.3%). The most common isolated organisms were
      Staphylococcus aureus (30.4%), Salmonella species (21.7%), Pseudomonas species
      (13.0%), and Klebsiella species (13.0%). The care rate was 94.7%. Death occurred
      in 2 patients. Lupus activity, impaired renal function, and cytotoxic therapy did
      not predispose to infection.

PMID- 8153687
TI  - Moraxella catarrhalis respiratory infection in adults.
AB  - Moraxella catarrhalis (MC) is an upper respiratory tract commensal which may also
      be pathogenic. In this report we examined the clinical features, microbiology and
      therapeutic response in 30 consecutive adult patients with pneumonia who had MC
      isolated in the sputum. The mean age was 66 years with an equal sex ratio. Most
      patients gave a history of cigarette smoking (77%) and had underlying pulmonary
      diseases (73%). Dyspnea and productive cough were the most common complaints
      (87%). Fever was a manifestation in 60% of patients. Chest X-ray features of
      pneumonia were noted in 78% of patients while leucocytosis (> 11,000/mm3) was
      evident in 70%. While all isolates were susceptible to tetracycline, 70% were
      resistant to penicillin/ampicillin by in-vitro testing. Three patients died, two
      from their underlying illnesses and one from myocardial infarct. We believe that
      MC isolated in sputum cultures from symptomatic adults with underlying
      respiratory diseases should be treated as a pathogen. The short term prognosis is
      good.

PMID- 8153688
TI  - Autologous marrow injection in the treatment of delayed and non-union in long
      bones.
AB  - A retrospective study of the use of autologous bone marrow injection for the
      treatment of delayed and non-union of long bones in an Orthopaedic Department,
      Singapore General Hospital from 1990-1991 is presented. There were 10 patients
      with 11 fractures (8 tibia and one each of humerus, femur and radius-ulna)
      available for study. Percutaneous injection of autologous marrow alone was used
      to stimulate healing of delayed and non-unions treated initially by plating,
      external fixation and in one case, by plaster cast. Marrow injection stimulated a
      callus formation sufficient to unite 9 of the fractures. The median time to
      clinical union was 10 weeks (range 4-23 weeks) and radiological union 17 weeks
      (range 9-29 weeks). Most patients had discomfort at the donor and injected sites
      for one to two days. There was one case of infection but none of the significant
      donor site morbidity was associated with standard open autologous grafting. Bone
      marrow injection was effective in stimulating bony union, with numerous
      advantages and considerably lower morbidity compared with standard open
      autologous grafting. Shorter inpatient stay was a significant feature.

PMID- 8153689
TI  - Common toxicities of cancer chemotherapy.
AB  - Sixty cancer patients who were receiving chemotherapy at an outpatient Oncology
      Centre were surveyed for their views on a list of treatment-related toxicities.
      The severity of each toxicity was assessed using a visual analogue scale. Sixty
      percent of patients felt that the overall toxicity was acceptable. Ten percent
      felt like giving up. Problem with venous access was named the worst toxicity by
      37% of patients, followed by nausea and vomiting (19%), and long waiting time
      (11%). Male patients tended to tolerate chemotherapy better. The female patients
      were significantly more affected by hair loss than their male counterpart. Better
      understanding of the toxicities of chemotherapy as perceived by the patients
      themselves allows them to take appropriate measures in improving their quality of
      life.

PMID- 8153690
TI  - Tibial tuberosity fractures in adolescents.
AB  - Tibial tuberosity fracture is uncommon. We reviewed five patients with the
      injury, presenting over a two-year period. All of them were adolescent boys who
      sustained the injuries during sport. They were treated with open reduction and
      internal fixation using cancellous screws with additional tension band wiring for
      comminuted fragments. Results were excellent, with complete union of fracture
      site, full range of movement by three to five months and no evidence of
      complication on follow-up for thirty months.

PMID- 8153691
TI  - Cutaneous mastocytosis in Singapore.
AB  - Mastocytosis is the collective name for a group of clinical syndromes whose signs
      and symptoms are due to the infiltration of various tissues by mast cells and to
      the release of chemical mediators by these cells. The skin is the most frequently
      affected organ. Skin manifestations include urticaria pigmentosa, mastocytoma,
      diffuse cutaneous mastocytosis and telangiectasia macularis eruptiva perstans.
      Seven cases of mastocytosis were seen over a 3-year period at the National Skin
      Centre from 1989 to 1992. All our patients were in the paediatric age group.
      There were four boys and three girls ranging in age from one year to five years.
      The mean age of onset of the disease was 2.3 months. Six patients presented with
      cutaneous signs and symptoms of urticaria pigmentosa and one patient had diffuse
      cutaneous mastocytosis. Itch was the most prominent symptom seen in all the
      patients. All the patients had a positive Darier's sign, pathognomonic for
      mastocytosis. None of the patients had a positive family history. Treatment was
      conservative and symptomatic, with the use of H1 antihistamines to control
      itching. A particularly important aspect of management is the avoidance of
      triggering factors. All our patients have remained well with only skin
      involvement. The prognosis for children with mast cell disease is good, with at
      least half of the children with urticaria pigmentosa experiencing reduction of
      symptoms and lesions by adolescence.

PMID- 8153692
TI  - Atrial arrhythmias post coronary bypass grafting.
AB  - Atrial arrhythmia is a relatively common complication post coronary bypass
      grafting. A retrospective study of 400 patients who had undergone coronary
      arterial bypass grafting over a period from June 1989 to December 1990 were
      studied to determine the incidence of atrial arrhythmias in an Asian population.
      The incidence of atrial arrhythmias post coronary artery bypass grafting was
      14.25% (57 out of 400 patients). The commonest type of atrial arrhythmia was
      atrial fibrillation (82.5%), followed by supraventricular tachyarrhythmia (14.0%)
      and atrial flutter (3.5%). The preoperative state of the myocardium, intra
      operative ischaemia to the myocardium and hypokalemia were found to be the
      possible contributory factors to the development of atrial arrhythmias.

PMID- 8153693
TI  - Nasal septal abscess--retrospective analysis of 14 cases from University
      Hospital, Kuala Lumpur.
AB  - Fourteen patients who presented to the University Hospital of Kuala Lumpur
      between June 1981 and June 1991 were reviewed retrospectively. Nasal septal
      abscesses are uncommon and therefore there are limited reports in the medical
      literature. Early diagnosis and immediate therapy is mandatory to avoid cosmetic
      nasal deformity or intracranial infection. Two out of the fourteen patients
      developed saddle nose deformity and septal perforation because of delay in
      treatment, the cases were misdiagnosed by non-otolaryngologist as turbinates
      swelling. The leading cause of nasal septal abscess was non-surgical trauma which
      accounted for about 85.7%. The commonest pathogenic organism isolated from the
      pus of nasal septal abscess was Staphylococcus aureus.

PMID- 8153694
TI  - Growing skull fractures.
AB  - Two recent cases of growing skull fractures are presented and the literature
      reviewed. Skull fractures in children which are at risk of enlarging should be
      recognised and followed up closely.

PMID- 8153695
TI  - Primary gastric lymphoma.
AB  - Primary gastric lymphoma is a rare gastrointestinal lymphoma. The treatment of
      this condition remains controversial, especially the extent of surgical
      resection. Ten cases were operated on over a five-year period at our institution
      and the outcome was reviewed. Early results suggest no difference in survival
      whether the margin of resection was clear or not so long as postoperative
      chemotherapy was given. The outcome appear to depend more on the extent of the
      disease at the time of surgery. Full thickness involvement of the stomach wall
      with lymph node involvement were bad prognostic indicators.

PMID- 8153696
TI  - Management of grief.
AB  - This article classifies grief into uncomplicated and complicated grief. A review
      of the psycho-analytic literature, recent studies on incidence, stages and
      developmental aspects of normal grief, the phenomenology and psychopathology of
      complicated grief, and the total management of grief amongst psychiatric
      patients, is presented. Complicated grief, classified as delayed, prolonged and
      distorted grief is described. As there is increased morbidity and mortality, the
      need for psychiatric intervention is necessary. The treatment of pathological
      grief includes grief counselling, brief dynamic psychotherapy, group
      psychotherapy, and family work. In addition to psychotherapy, for mental illness
      accompanying grief, biological treatment such as drugs should not be avoided.
      Therapeutic work with bereaved patients include the empathic approach, active
      listening, encouragement of verbal expression of affect, giving permission to
      grieve, and maintenance of therapeutic neutrality. Adequate attention must be
      given to analysis of counter transference and case supervision of the student
      therapist.

PMID- 8153697
TI  - A practical approach to the management of depression.
AB  - Depression is a common and treatable condition. Failure to diagnose it may lead
      to unnecessary investigations, delay in treatment and an increased risk of
      suicide. Anti-depressant drugs are the first line of treatment. Tricyclics are
      generally the drugs of choice as their efficacy is very well established. Second
      generation antidepressant drugs are preferred for the elderly and those with
      heart disease as they tend to have milder side effects and are less toxic in
      overdose. Electroconvulsive therapy is indicated in those with severe depression,
      high suicide risk or failed drug treatment. Psychotherapy is usually used as an
      adjunct to pharmacotherapy whilst lithium is used to prevent recurrence of
      depression.

PMID- 8153698
TI  - Q waves in inferior limb leads--? Acute myocardial infarction. Wolff-Parkinson
      White syndrome.

PMID- 8153699
TI  - Transjugular intrahepatic portosystemic shunt: a case report.
AB  - Of the various methods currently available to manage potentially life threatening
      bleeding from oesophagogastric varices, surgical portosystemic shunts are
      recognised to have the lowest incidence of rebleeding though surgery is
      associated with high morbidity and mortality. Recently, a promising non-surgical
      technique has been developed to create an intrahepatic portosystemic shunt via a
      percutaneous transjugular route. This paper presents a case report of this
      region's first transjugular intrahepatic portosystemic shunt procedure and
      briefly reviews the development and preliminary results of this technique.

PMID- 8153700
TI  - Fatal Chromobacterium violaceum septicaemia.
AB  - A 19-year-old Malay male succumbed to a septicaemia caused by Chromobacterium
      violaceum 11 days after onset of illness. The organism is a common soil
      saprophyte and may be considered as contaminant on culture. It is essential to
      recognise its clinical significance in purulent processes so that appropriate
      therapy can be instituted. We report the first fatal case of Chromobacterium
      violaceum infection in the University Hospital, Kuala Lumpur.

PMID- 8153701
TI  - Case report--a neonate with nonimmune hydrops fetalis.
AB  - A post-dated intra-uterine growth retarded male Malay baby was born to a 30-year
      old mother gravida II by Caesarean section. Her previous pregnancy ended in still
      birth. The baby was severely asphyxiated at birth. He was intubated and
      immediately admitted to the neonatal intensive care unit. He had anasarca,
      anaemia, purpura and firm, massive hepatosplenomegaly. X-rays revealed ascites
      and bilateral metaphysiitis of the long bones. The haemoglobin level was 5.0
      gm/dl and PCV 18.3%. Coombs' test was negative. Prothrombin time (PT) and partial
      thromboplastin time (PTT) were prolonged. The baby and mother were positive for
      Venereal Disease Research Laboratory (VDRL) and the treponema pallidum
      haemagglutination assay (TPHA) tests. The baby was actively resuscitated but
      expired at three and a half hours of life due to overwhelming sepsis associated
      with severe anaemia and disseminated intravascular coagulation.

PMID- 8153702
TI  - Ascarid worms causing recurrent cholangitis in a patient with an obstructing
      ampullary tumour.
AB  - This is a report of a 57-year-old Malay lady who presented with recurrent
      episodes of cholangitis and septicaemia. A dilated biliary tree caused by a
      stenosing periampullary tumour was found to contain adult round worms. A
      pancreatico-duodenectomy was performed following biliary decompression. Ascarid
      worms are a rare cause of cholangitis in malignant biliary obstruction.

PMID- 8153703
TI  - Augmentin-induced cholestatic jaundice--a case report.
AB  - A case of cholestatic jaundice following treatment with Augmentin is reported.
      The awareness of hepatotoxicity due to drug should help to avoid unnecessary
      invasive procedures in the evaluation of this reversible condition.

PMID- 8153704
TI  - Non-puerperal uterine inversion--a case report.
AB  - A rare case of non-puerperal uterine inversion caused by a large fundal leiomyoma
      in a 36-year-virgo intacta resulting in intractable haemorrhage was reported.
      After a myomectomy, attempts to reduce the inversion vaginally by transecting the
      anterior and posterior cervix was unsuccessful and a laparotomy was performed.
      The inversion was successfully corrected with return of normal function of the
      uterus.

PMID- 8153705
TI  - Use of urinary red cell morphology in determining the source of haematuria.

PMID- 8153706
TI  - Urinary erythrocyte morphology as a diagnostic aid in haematuria.
AB  - The value of urinary erythrocyte morphology in diagnosing glomerular and
      nonglomerular haematuria was studied using phase contrast microscopy in 105
      patients with significant haematuria. Fifty-eight (93.6%) out of 62 patients with
      glomerulonephritis had dysmorphic erythrocytes and 40 (93.1%) out of the 43
      patients with nonglomerular disease had isomorphic erythrocytes in the urine. A
      mixed picture of glomerular and nonglomerular haematuria was seen in 5 patients.
      The sensitivity was 93.6%, the specificity was 97.7% and the positive predictive
      value was 98.3% for glomerulonephritis in patients with dysmorphic haematuria.
      The positive predictive value for a nonglomerular source of bleeding was 96.7%
      with isomorphic haematuria. It is concluded that phase contrast microscopic
      examination of erythrocytes in urine is a simple, inexpensive and noninvasive
      technique that reliably distinguishes between glomerular and nonglomerular
      bleeding in patients.

PMID- 8153707
TI  - Education and myopia in 110,236 young Singaporean males.
AB  - Computerised data of 110,236 Singaporean males aged 15 to 25 (mean 17.75) years
      who underwent compulsory medical examination from April 1987 to January 1992 were
      used to estimate the prevalence and severity of myopia among young Chinese,
      Malay, Indian and Eurasian Singaporean males with different educational levels.
      The prevalence and severity of myopia amongst the groups with different
      educational levels were compared. These groups were fairly well-matched for
      important known confounding factors such as age, sex, race and degree of
      urbanisation of place of residence. Our data showed a positive association
      between educational attainment and both the prevalence and severity of myopia.
      Both the prevalence of myopia and the proportion of myopes with severe myopia
      were in general higher among those with more years of formal education.

PMID- 8153708
TI  - Rapid desktop method for the measurement of glycated haemoglobin HbA1c.
AB  - A new desktop monoclonal antibody-based test system (Bayer Diagnostics DCA 2000)
      for quantitation of glycated haemoglobin HbA1c is described and evaluated. This
      method involves a monoclonal antibody to HbA1c which defines its specificity. It
      requires 9 minutes to complete, and shows good intra- and inter-run precisions
      (1.3%-3.7%), at 5 HbA1c levels tested--4.1%, 5.7%, 6.1%, 9.2% and 12.4%. Results
      from 81 blood samples obtained from diabetic patients (3.9%-13.2% HbA1c) showed
      excellent correlation with a laboratory-based ion-exchange HPLC technique (y =
      1.03 [Lab] + 0.103%; Pearson coefficient, r = 0.99). The test can be performed
      either with a capillary fingerprick or venous blood sample. Only 1 microliter of
      blood volume is required. Comparison of HbA1c levels of 43 paired capillary and
      venous samples showed excellent correlation (y = 1.00 [venous] + 0.042%; r =
      0.99). The HbA1c values obtained from a cohort of 37 healthy adults, mean (+/-
      SD) age 33 +/- 9.01 years, gave a value of 5.5 +/- 0.42%. The calculated 95%
      confidence limits are 4.7%-6.3%. This quick method provides 'stat' HbA1c results,
      which were hitherto not possible with the laboratory-based methods.

PMID- 8153709
TI  - Calculating the GP consultation fee in Singapore: towards a rational costing
      approach.
AB  - PURPOSES: The General Practitioner (GP) consultation fee in Singapore, unlike
      that of his specialist colleague, has been left very much undefined over the
      years. There is a need for an objective way of calculating the GP consultation
      fee. METHOD: A proposed method of calculating the GP consultation fee based on
      the model of estimating the total cost of producing the service plus the doctor's
      remuneration is described. Known prevailing costs were used in the computation.
      This model allows us to work out the cost to the patient by dividing the total
      cost of producing the service by the number of patients (referred to as patient
      encounter load) seen by each duration of consultation--4, 6, 10, 15 and 30
      minutes. Different monthly remuneration levels for the doctor were used to
      compute the different consultation fees that would result for each of the
      duration of consultations. RESULTS: Using this method of calculation, for a
      doctor with a desired monthly remuneration of $7000, and seeing a patient every 6
      minutes over a 150-hour month, the consultation fee is $13.00. This drops to
      $11.00 if the doctor receives a remuneration of $4000 per month. Using the same
      parameters, a 15 minute consultation will cost the patient $30.00 and $25.00
      respectively. CONCLUSION: This method can be used to derive a consultation fee
      for services requiring different durations and varying remuneration brackets for
      the doctor.

PMID- 8153710
TI  - Hb E beta +-thalassaemia in west Malaysia: clinical features in the most common
      beta-thalassaemia mutation of the Malays [IVS 1-5 (G-->C)].
AB  - Patients with the Hb beta + [IVS 1-5 (G-->C)] clinically presented as beta
      thalassaemia intermedia and remained asymptomatic in the absence of blood
      transfusions. With or without blood transfusions the patients were short and had
      moderate to marked thalassaemia facies. Children who received blood transfusions
      showed progressive iron loading with age. The serum ferritin and serum alanine
      transaminase levels were significantly raised in the patients who were given
      blood transfusions. In the presence of blood transfusions, and absence of
      adequate iron chelation therapy, splenectomy became an inevitable event at some
      stage of the disease because of increasing transfusing requirements.

PMID- 8153711
TI  - Nicotine-replacement products in smoking cessation: a review.
AB  - Smoking cessation programmes have gained greater prominence in Singapore in the
      face of growing desire among smokers to stop smoking. There exists a whole
      plethora of different methods which are employed in smoking cessation; this
      reflects the fact that smoking is a compulsive habit which is difficult to stop.
      Most attempts at smoking cessation fail, and the failure is largely attributable
      to the addictive properties of nicotine, which causes a withdrawal syndrome when
      the body is deprived of it. A host of medications have been used in the past in
      an attempt to alleviate this withdrawal syndrome. Of these products, perhaps the
      most promising are the nicotine-replacement products. These products consist of
      nicotine which is delivered through contrasting delivery systems viz polacrilex
      gum, transdermal patches, nasal sprays and inhalers. A review of recent clinical
      trials assessing the efficacy of the nicotine gum and the transdermal nicotine
      patch was conducted. Of the two products, the transdermal nicotine patch seems to
      have superior pharmacokinetics and fewer side-effects, and may well be the
      product of choice.

PMID- 8153712
TI  - Comparison of the results of spinal fusion for spondylolisthesis in patients who
      are instrumented with patients who are not.
AB  - Eighty-five patients who had surgery for spondylolisthesis were studied
      retrospectively both clinically and radiologically to determine if
      instrumentation lead to better fusion rates and clinical outcome. Degenerative
      spondylolisthesis accounted for 57 cases and patients who had instrumentation did
      have a better fusion rate and clinical outcome, with 60% of patients having
      complete relief from pain. In the group with isthmic spondylolisthesis (28
      patients), there was also an improved fusion rate with instrumentation. However,
      these patient took a longer time before returning to work and had to be protected
      in a polythene brace. The improved fusion rate radiologically with
      instrumentation did not translate to better clinical results with regard to pain
      relief and disability. One patient developed ascending epidural haematoma with
      instrumentation and resulted in paraplegia. She had incomplete recovery during
      the follow-up.

PMID- 8153713
TI  - Follow-up study of transsexuals after sex-reassignment surgery.
AB  - INTRODUCTION: This is a follow-up study of 45 male and 36 female sex reassigned
      transsexuals. METHOD: The subjects were interviewed before and 1 to 8 years
      following sex reassignment surgery. RESULTS: When first seen the males (mean age
      23.8 years) were slightly younger than females (mean age 24.9 years). The males
      had less education and held lower level jobs. They started their sexual life
      about 1-2 years earlier, but they cross-dressed 4-7 years later than the females.
      The follow-up results showed that 35% were married and all of them had no
      problems adjusting to their new life. The overall results were 56% very good and
      44% good. There is no pre-operative variables that can predict good adjustments
      for female transsexuals. For male transsexuals, earlier age of transsexual
      manifestation was related to good post-operative adjustments. DISCUSSION: The
      females were less satisfied with the surgery, but they adjusted well as the
      males. The results were comparable with those from previous studies.

PMID- 8153714
TI  - Ankylosing spondylitis in Singaporean Chinese--a clinical profile.
AB  - The clinical characteristics of 38 local Chinese ankylosing spondylitis patients
      were studied by interview, clinical examination and review of casenotes. The sex
      ratio was 3.2:1 in favour of males. The average duration from onset of symptoms
      till diagnosis of disease was 7.25 years. Peripheral joint involvement occurred
      in 71% of the patients. Extra-articular complications were uncommon; only three
      patients had a history of uveitis and one patient had biopsy proven IgA
      nephropathy. 26.3% of patients had significant disability due to the disease.
      Early diagnosis of the disease should be made as it may improve the prognosis of
      the patients.

PMID- 8153715
TI  - Pulmonary function in symptom-free asthmatics.
AB  - Seventy-five adult asthmatic patients with clinical remission underwent
      spirometry. Only 8.3% of the subjects demonstrated normal spirometry. The others
      had reduced vital capacity (VC), forced vital capacity (FVC), forced expiratory
      volume in one second (FEV1), maximum mid-expiratory flow rate (MMF) and peak flow
      rate (PEFR). This study demonstrates that asthma can cause irreversible airflow
      obstruction and there is a poor relationship between symptoms in asthmatics and
      their respiratory function test results.

PMID- 8153716
TI  - Pattern of antibiotic usage in hospitals in Malaysia.
AB  - A prospective survey of antibiotic prescribing patterns in six Ministry of Health
      general hospitals in Malaysia was undertaken. Information on antibiotic
      prescriptions including the types of antibiotics used and the purposes for
      prescription was obtained through the use of questionnaires. A total of 1,918
      antibiotic prescriptions were available for analysis. About two-thirds of
      prescriptions were for therapeutic purposes. The most common infections treated
      were lower respiratory infection (31%), followed by skin and soft tissue
      infection (17%), and urinary tract infection (8%). Only 20% of the therapeutic
      prescriptions were based on microbiological test results. Prophylactic
      prescriptions were issued for a variety of indications, the most common being
      toilet and suture of wounds. Only 5% of prophylactic prescriptions were of less
      than 3 days duration. There was great diversity in antibiotics and antibiotic
      regimens employed. It was evident that there was a lack of compliance with
      guidelines on antibiotic use issued by the Ministry of Health.

PMID- 8153717
TI  - Ambulance response time to emergency departments.
AB  - The study was conducted to ascertain the time it takes an ambulance team to reach
      a patient and transport the patient to an emergency department after a 995 call.
      One hundred and sixty-two cases brought to two emergency departments (Singapore
      General Hospital and Tan Tock Seng Hospital) between 11 March 1992 and 16 March
      1992 were studied. The information was obtained from ambulance officers of the
      Singapore Civil Defence Force. It took an average of 11.40 +/- 4.88 minutes for
      an ambulance team to reach a patient and 30.50 +/- 10.62 minutes for the patient
      to reach an emergency department after a 995 call. With the present level of
      staff in Singapore, basic life support care starts 11.40 minutes and advanced
      life support care 30.50 minutes after a 995 call. These times are unacceptable if
      it involves a cardiac arrest or a trauma patient. Factors which cause these long
      time intervals include traffic congestion, inadequate public education, location
      of patient (whether on ground level or highrise) and distance from the emergency
      departments.

PMID- 8153718
TI  - Therapeutic regimes for acute bronchial asthma.
AB  - No uniform guidelines currently exist for the initial drug therapy of asthma or
      for the criteria to assess efficacy of initial therapy. A study with 71 subjects
      aged between 15 and 40 years was conducted to compare the usefulness of three
      commonly used asthma treatment regimes, viz subcutaneous adrenaline, nebulised
      salbutamol and intravenous aminophylline. Parameters used to monitor response
      were pulse rate (PR), respiratory rate (RR), Peak Expiratory Flow Rate (PEFR) and
      Patient's Subjective Assessment Scale (PSAS). All patients in the three treatment
      groups were comparable at pre-treatment, except for the Salbutamol group which
      appeared to have asthma of a milder severity based on PSAS scores alone.
      Following treatment, improvements were noted in Peak Flow Rate and PSAS. These
      improvements were greatest in those groups treated with salbutamol and adrenaline
      (p = 0.04 for PEFR and 0.01 for PSAS). Salbutamol treated patients also had
      significant improvements in Respiratory Rate (p < 0.05). The results were not
      conclusive as to whether adrenaline or salbutamol was the superior drug.
      Salbutamol and adrenaline are preferred to aminophylline in the initial treatment
      of acute bronchial asthma.

PMID- 8153719
TI  - The day release scheme at View Road Hospital.
AB  - Psychiatric rehabilitation has been carried out in View Road Hospital since 1975.
      The training and programmes have been developed over the years and are now
      individualised according to each patient's abilities, handicaps and needs. The
      various steps in rehabilitation are outlined. The emphasis in View Road Hospital
      is on work rehabilitation and social functioning so that the patient can adapt to
      outside life. Its success is reflected in the Day Release Scheme. Of the 250
      patients in View Road Hospital, 92 patients are now on this Day Release Scheme.
      The majority are young (30-49 age group) and have secondary education. The
      criteria for this scheme are described.

PMID- 8153720
TI  - Colonic anastomosis with sutureless biofragmentable rings.
AB  - PURPOSE OF STUDY--To evaluate the safety and applicability of a biofragmentable
      anastomotic ring (VALTRAC BAR) in an Asian population and report on its
      performance as an alternative to sutures and stapling devices. SELECTION OF STUDY
      SUBJECTS--A consecutive series of 20 patients undergoing colonic surgery over a 7
      month period from October 1992 to April 1993. OBSERVATIONAL METHODS AND MAIN
      FINDINGS--A protocol was drawn up for prospective record of data from 11 male and
      9 female patients (age 34 years to 83 years). Information was collected regarding
      length of operation (average 3 hours), actual anastomotic time (average 13.5
      minutes) and problems or complications associated with the Valtrac device during
      surgery (none). Postoperatively, the cases were carefully documented for
      intestinal obstruction from faecal impaction due to Valtrac fragments (none), the
      timing of bowel movements (majority 4th day, range 1-7 days), and awareness of
      passing fragments (none). There were no mortality and no anastomotic leakage
      though two patients developed wound infection. PRINCIPAL CONCLUSIONS--This
      preliminary study confirms that the biofragmentable anastomotic ring is a simple,
      rapid and efficacious method of bowel anastomosis comparable to existing
      procedures. It has the distinct advantage of being uniformly reproducible.

PMID- 8153721
TI  - Bilio-enteric anastomoses: results in benign and malignant conditions.
AB  - Twenty bilio-enteric anastomoses were performed or managed from May 1990 to
      December 1992. Recurrent pyogenic cholangitis (RPC) and pancreatic cancer were
      the commonest conditions which required drainage procedures. Roux-en-Y hepatico
      jejunostomy (RHJ) was performed in 9 patients, 4 for RPC, one for pancreatic
      cancer, another for a cholangiocarcinoma, 2 following excision of choledochal
      cyst and one hepatico-jejunostomy was part of a Whipple reconstruction. Roux-en-Y
      side to side choledocho-jejunostomy (CDJ) was performed in one patient.
      Choledocho-duodenostomy (CDD) was performed in 6, 4 for obstructive jaundice due
      to choledocholithiasis, one for RPC and one in a choledochal cyst. One patient
      operated elsewhere presented with complications after a CDD. Palliative
      cholecysto-jejunostomy (CYJ) was carried out in 4 patients with pancreatic
      malignancy. All benign conditions were treated by hepatico-jejunostomy and
      choledocho-duodenostomy, while three patients with malignant conditions were
      treated by hepatico-jejunostomy. Permanent subcutaneous access loops were
      provided when recurrent problems were anticipated, 4 in RPC and one after
      subtotal resection of a cholangiocarcinoma. Based on this study, we found Roux-en
      Y hepatico-jejunostomy a versatile drainage procedure, which was useful in both
      benign and malignant diseases.

PMID- 8153722
TI  - The false positive Lachman test.
AB  - Five patients with isolated rupture of the posterior cruciate injury following
      road traffic accidents were noted to demonstrate a "positive Lachman test".
      Stress radiographs while performing the Lachman manoeuvre confirmed that all 5
      patients had only a posterior cruciate injury. Attention is drawn to the "false
      positive Lachman test" that indicates a posterior cruciate injury. The presence
      of a sag sign also establishes a diagnosis of posterior cruciate rupture and a
      positive Lachman test in this situation must be interpreted with caution.

PMID- 8153723
TI  - Management of sexual disorders.
AB  - Sexual disorders comprise (a) disorders of function in which sexual functioning
      is disturbed leading to problems during sexual intercourse, (b) disorders of
      orientation whereby a non heterosexual partner or object is sought, and (c) other
      disorders involving aberrant psychosexual behaviour. In managing such problems a
      thorough psychosexual assessment is required in order to ascertain the exact
      nature of the problem and what the precipitating, predisposing and prolonging
      factors are. In disorders of orientation and disorders involving aberrant sexual
      behaviours, the developmental history and early childhood relationships must be
      looked into carefully. Laboratory investigations are usually indicated in
      erectile dysfunction as up to 80% would have an organic aetiology--vascular,
      neurological and endocrine disorders have to be ruled out. Treatment of the
      various conditions involves general sexual counselling, behaviour therapy
      including stress management, psychotherapy, marital therapy and drug therapy as
      indicated. However, in erectile dysfunction, drug treatment (including
      intracavernosal injections), mechanical aids, or surgery may be indicated; and in
      transsexualism--for those who are unable to revert to accepting their natural
      status--a sex reassignment operation is the treatment of choice.

PMID- 8153724
TI  - Psychiatric referrals in the general hospital.
AB  - Psychiatric disorders and physical illnesses often coexist. Although there is
      evidence of high psychiatric morbidity in general hospital patients, only a small
      percentage are referred to the consultation-liaison psychiatrist. The paper
      describes and discusses the common psychiatric conditions encountered and
      referred in general hospitals. They include attempted suicides, psychiatric
      disorders presenting with physical symptoms, organic psychiatric disorders
      presenting with psychiatric symptoms and the psychiatric consequences of physical
      illness. The major diagnostic categories of these referrals are organic psychotic
      disorders, functional psychoses and neurotic disorders. Some broad guidelines are
      listed for the referring physician. Patients presenting with suicidal ideations
      or attempts, suspected emotional psychiatric disturbance, a history of
      psychiatric illness, an apparent incompetence in giving consent for medical
      procedures and those with diagnostic and management problems could be referred to
      the psychiatrist.

PMID- 8153725
TI  - Bundle branch block and syncope? Right bundle branch block with left anterior
      hemiblock and prolonged PR interval-trifascicular block.
AB  - An 84-year-old Indian man was admitted with a history of recurrent episodes of
      giddiness for the last 5 years. He also had 3 previous episodes of transient loss
      of consciousness. He has a history of hypertension for the past 28 years and
      angina pectoris for the past 10 years. The clinical examination was unremarkable
      and no postural hypotension was detected. The electrocardiogram is illustrated in
      Fig 1.

PMID- 8153726
TI  - Accidental cannulation of the hepatic vein during pulmonary artery
      catheterisation--a case report.
AB  - A 22-year-old male was admitted to the adult ICU with a diagnosis of massive
      cardiomegaly and a large left ventricular thrombus, and needed Swan-Ganz
      catheterisation for proper haemodynamic monitoring. Insertion of the Swan-Ganz
      catheter resulted in hepatic vein cannulation. Pulmonary artery was successfully
      cannulated only when the patient was put in the head-up and right lateral
      position. It is suggested that to increase the success rate of patients with low
      cardiac output, cardiomegaly or pulmonary hypertension, they be placed in a head
      up and right lateral position.

PMID- 8153727
TI  - Benign persistent pneumoperitoneum in systemic sclerosis.
AB  - We describe a 50-year-old Chinese woman who had severe gastrointestinal
      manifestations from systemic sclerosis complicated by spontaneous
      pneumoperitoneum in the absence of either visceral perforation or pneumatosis
      cystoides intestinalis. This is a rare complication of systemic sclerosis; only
      four other cases have been reported. Recognition of this condition is important
      so as to avoid unnecessary surgery.

PMID- 8153728
TI  - Burnisher's asthma--a case due to ammonia from silverware polishing.
AB  - A 39-year-old man with no past or family history of asthma developed asthmatic
      symptoms five months after working as a burnisher in a hotel. He polished brass
      or silverware using "brasso" or "silvo" respectively. He noticed symptoms only
      when using "silvo". Specific bronchial provocation testing (BPT) to "brasso" was
      negative. Specific BPT to "silvo" produced a dual asthmatic reaction. Ammonia was
      present in both polishes. The ammonia-in-air levels during polishing was 8-15 ppm
      with "silvo" and less than 1 ppm with "brasso". A specific BPT to 12 ppm of
      ammonia produced an immediate asthmatic reaction. Our opinion is that he had
      occupational asthma from the ammonia liberated while polishing silverware with
      "silvo". Ammonia has been reported to cause asthma. However, there have been no
      previous reports of occupational asthma among burnishers doing silver polishing.

PMID- 8153729
TI  - Congenital posterior mediastinal teratoma--a case report.
AB  - Almost all mediastinal teratomas are found in the anterior mediastinum. We
      describe a case of a 41-day-old baby girl who had teratoma in the posterior
      mediastinum. She presented at the age of 6 days with the problem of progressive
      jaundice and was found to have septicaemia. During septic screening, chest X-ray
      revealed a mass in the right mediastinum. Ultrasound and CT-scan of the chest
      showed a multiloculated mass at the right posterior mediastinum. Fine needle
      aspiration biopsy of the mass confirmed a teratoma.

PMID- 8153730
TI  - Fibro-inflammatory pseudotumour in the maxillary sinus.
AB  - We describe a rare case of fibro-inflammatory pseudotumour in the right maxillary
      sinus of a 13-year-old Chinese girl who presented with proptosis and radiological
      appearance suspicious of malignancy but was histologically benign. She underwent
      Caldwel-Luc operation and received prolonged steroid therapy. She is now free of
      the disease both clinically and radiologically 33 months after cessation of
      therapy.

PMID- 8153731
TI  - Massive haemothorax as a complication of primary lung cancer--a case report.
AB  - A 58-year-old man was admitted with a massive haemothorax. At thoracotomy, the
      cause was found to be due to a bleeding primary lung cancer, the cell type of
      which was adenocarcinoma. A literature search revealed that this complication of
      lung cancer has not previously been described. Reasons as to the infrequency of
      this complication are discussed.

PMID- 8153732
TI  - A review of anaesthesia in ophthalmology.

PMID- 8153733
TI  - The Florida pouch.

PMID- 8153734
TI  - Treatment options for prostate cancer.
AB  - The reader of the prostate cancer literature is often stunned by the lack of
      evidence of efficacy of one form of treatment over that of others. Indeed,
      information suggests that "no treatment" may be an effective option. Analyzing
      the available literature that reports the results of treatment versus observation
      for prostate cancer, Fleming et al. from the Prostate Patient Outcomes Research
      Team found that in most cases, treatment offered less than a 1-year improvement
      in quality-adjusted life expectancy. Using less optimistic assumptions, the
      authors also found that treatment could actually reduce quality-adjusted life
      expectancy. The decision of what form of treatment to offer the individual
      patient requires considerable discussion with the patient concerning his
      priorities and goals of therapy. For the younger patient with localized disease,
      the prevailing trend in the United States is toward radical prostatectomy. As the
      patient approaches the age of 70 years, the advantages of treatment versus
      observation alone evaporate. Because the disease is often of low biologic
      potential with a long doubling time, the option of observation initially with
      serial determinations of PSA is not unreasonable. If a slow rate of rise is
      noted, some patients may elect observation. However, with more rapid rises in
      PSA, a more aggressive stance may be appropriate. Because of the uncertainties
      inherent to treating this disease, it is imperative that the patient be brought
      into the treatment planning through education and through extensive discussions
      with health care providers and with family members. Only through such informed
      and deliberate discussions can a plan for treatment be reached with which the
      patient will be comfortable.

PMID- 8153735
TI  - Randomized study of the effect of midnight removal of urinary catheters.
AB  - This study shows that removal of urinary catheters at midnight has several
      advantages over removal at 6 AM. The midnight group had a significantly greater
      initial voided volume and a longer time to first void than the equivalent 6 AM
      group. Advantages to midnight catheter removal also exist for nursing staff.
      Midnight tends to be less busy on the nursing unit compared with 6 AM, thus
      making it a preferable time for performance of routine tasks. Catheter removal at
      midnight also allows for convenient observation of patient voiding and assessment
      earlier in the day. This means that any necessary intervention can take place
      during working hours when more staff are on duty. There is also the potential for
      earlier discharge, with economic benefits related to shorter bed stay and more
      efficient discharge planning. We believe midnight catheter removal offers
      considerable benefits over the traditional 6 AM time on both general and urology
      units.

PMID- 8153736
TI  - Bigger is not better: a case in point.

PMID- 8153737
TI  - The stay clean flap.

PMID- 8153738
TI  - Backloading made easy.

PMID- 8153739
TI  - Perioperative information for radical prostatectomy patients.

PMID- 8153740
TI  - Soft sculpture model for teaching pelvic muscle exercises.

PMID- 8153741
TI  - "Spina bifida, Part 3. Bladder and bowel management".

PMID- 8153742
TI  - Effects of irrigation fluid warming on hypothermia during urologic surgery.

PMID- 8153743
TI  - Railway suicide in England and Wales, 1850-1949.
AB  - According to the official statistics of the Registrar General, the first railway
      suicide occurred in 1852 and more than 10,000 suicides recorded during the period
      1852-1949. Throughout this time the number of male cases always exceeded the
      number of female cases and the railway accounted for a greater proportion of male
      than female suicides in all but two years. By the early decades of the twentieth
      century, the railway was used in 5-6% of male suicides and 3-4% of female
      suicides. The incidence of railway suicide was correlated with the growth of the
      railway system offering some evidence for the relationship between availability
      of a lethal means and suicide rates.

PMID- 8153744
TI  - The epidemiology of suicide on the London Underground.
AB  - A database containing details of every incident of suicidal behaviour on the
      London Underground railway system between 1940 and 1990 was assembled from the
      records of London Underground Ltd and the British Transport Police. The total
      number of cases was 3240. The mean annual number of suicidal acts on the London
      Underground system increased from 36.1 (1940-1949) to 94.1 (1980-1989). There
      were significantly fewer incidents on Sundays than on the other days of the week
      and the daily rate was highest in the spring. 64% of incidents involved males and
      the peak age group for both sexes was 25-34 yr. Suicide verdicts were returned
      for a greater proportion of women than men. Overall case fatality was 55%.
      However, case fatality rates differed between stations, environmental factors
      appearing to influence survival. Possible strategies to prevent railway suicides
      and reduce the lethality of this method are discussed.

PMID- 8153745
TI  - Suicidal behaviour on railways in the FRG.
AB  - Between 1976-84 there were 6090 suicides and 391 attempted suicides on railways
      in the Federal Republic of Germany. This suicide method was compared to other
      methods with respect to seasonal and daily distributions and fluctuations by time
      of day for age and sex. The ratio of males to females was 2.54:1 and the relative
      incidence of this type of suicide as compared to the total number of suicides was
      high among the younger age groups. Investigation of seasonal variation revealed a
      peak for males in the autumn. There was a markedly higher incidence of railway
      suicides committed by males on Mondays and Tuesdays. This peak was less
      pronounced for females. Most incidents occurred in the evening hours (especially
      after sunset). An investigation of the relationship between the severity of
      injuries and the location of the suicide attempt revealed that those who
      attempted suicide on railway tracks in the countryside were more seriously
      injured than those whose attempt took place in or near main stations.

PMID- 8153746
TI  - Suicide in the Hong Kong subway.
AB  - Between 1979 and 1991, 56 suicides occurred within the Hong Kong subway system.
      Data on these fatalities, together with data on those who survived suicide
      attempts, are presented, along with guidelines established to assist the subway
      system staff in detecting, preventing and coping with such acts of self
      destruction.

PMID- 8153747
TI  - Psychiatric and preventative aspects of rail fatalities.
AB  - A previous survey of national rail fatalities and a sample of fatalities in
      southern England revealed many probable suicides and a small proportion of
      accidents. Epidemiological and clinical characteristics of this survey are
      reviewed in the light of general safety on British railways.

PMID- 8153748
TI  - A follow-up study of attempted railway suicides.
AB  - This paper reports the subsequent mortality of 94 persons who attempted suicide
      by jumping in front of London Underground trains between 1977 and 1979. The
      follow-up period was 10 yr. Despite the apparent seriousness of the method,
      completion of suicide was not found to be higher than in previous studies of
      attempted suicide by other methods. By the end of the follow-up period 18 persons
      had died, nine of natural causes. Coroners' inquests were held for the unnatural
      deaths. Seven verdicts of suicide and two of accidental death were recorded. Of
      the nine unnatural deaths four were from multiple injuries, three from drowning,
      one from asphyxia and one from acute narcotic poisoning. All four multiple injury
      deaths were women, three of these were from repeated incidents involving London
      Underground trains. The time interval between the index attempt and eventual
      death for the suicide/accident group ranged from 1 day to 43 months. For ethical
      reasons it was not possible to follow-up attempted suicides who were presumed to
      have remained alive.

PMID- 8153749
TI  - Preventing suicide on the London Underground.
AB  - A field study was carried out to investigate the possibility of preventing
      suicide on the London Underground. Four groups of potentially valuable measures
      were identified with the objectives of: (i) reducing public access to the tracks;
      (ii) improving surveillance by station staff; (iii) facilitating emergency stops;
      and (iv) reducing injury. These strategies are discussed.

PMID- 8153750
TI  - National suicide prevention programme and railway suicide.
AB  - Suicidal behaviour is a public health problem closely related to other problems
      such as mental illness, abuse, violence and accidents. This approach is
      illustrated by the prevention of railway suicides. A theoretical framework is
      sketched, which allows for the use of principles from injury prevention in the
      prevention of suicide. ICD-9 encoded death certificates from 1974, 1980, 1986 and
      1987 which concerned suicides and undetermined deaths on roads and railways were
      analysed (N = 294). Additional data were collected from autopsy, police and
      hospital protocols and from interviews with engine-drivers. Railroad victims
      dominated the sample (78% of cases). The mean age was 42 yr. Alcohol was detected
      in 27% of cases, drugs in 36% and severe illness (mostly psychiatric) in 57%. The
      relationship between types of collision and nature of injury is discussed.
      Environmental changes, such as changing the locomotive front design, are
      suggested as strategies for reducing accidents and suicides on railways.

PMID- 8153751
TI  - Imitative suicide on the Viennese subway.
AB  - The number of subway suicides in Vienna increased dramatically between 1984 and
      mid-1987. In the second-half of 1987 there was a decrease of 75% which has been
      sustained for 5 yr. This reduction in subway suicides began when a working group
      of the Austrian Association for Suicide Prevention developed media guidelines and
      initiated discussions with the media which culminated with an agreement to
      abstain from reporting on cases of suicide. The characteristics of suicide and
      attempted suicide on the Viennese subway are discussed and appropriate guidelines
      for media coverage of suicidal acts are presented.

PMID- 8153752
TI  - Psychological reactions of drivers to railway suicide.
AB  - Around 90 London Underground train drivers experience a person jumping or falling
      in front of their train each year. The majority of these incidents are suicides
      or attempted suicides. 76 drivers were interviewed in order to assess the range
      of responses to these incidents. The following psychometric instruments were
      used: Present State Examination (PSE9); Post-Traumatic Stress Disorder (PTSD)
      Interview; General Health Questionnaire (GHQ-28); Impact of Events Scale (IES);
      Post-Traumatic Symptom Scale; Recent Difficulties/Events scale; Perceived Stress
      Scale and Eysenck Personality Questionnaire (EPQ). When interviewed 1 month after
      the incident 13 (17.11%) drivers presented with PTSD. Diagnoses other than PTSD
      e.g. neurotic depression and phobic state were present in 24 (31.58%) drivers
      (including 12 of the 13 PTSD cases who had one additional diagnosis). On the
      basis of diagnoses three groups were identified: Group 1 drivers had PTSD and in
      most cases an additional PSE9 diagnosis; Group 2 drivers had a PSE9 diagnosis
      only; Group 3 drivers were not cases. 56 drivers were again interviewed 6 months
      after the incident to assess duration of caseness and/or symptoms and to identify
      any cases of delayed onset. Two drivers were still cases at 6 months (neurotic
      depression and phobic state), no driver presented with PTSD at 6 months. At 6
      months there was a significant drop in symptom scores compared with measures
      taken at 1 month. These results suggest that although approximately one-third of
      drivers suffered a severe psychological reaction following a railway suicide,
      when interviewed again 6 months after the incident most drivers reported a marked
      reduction in symptoms.

PMID- 8153753
TI  - 'Person under train' incidents from the subway driver's point of view--a
      prospective 1-year follow-up study: the design, and medical and psychiatric data.
AB  - From the subway driver's point of view, a 'person under train' (PUT) incident is
      a serious life event. This study focuses on the 1-yr consequences of such events.
      Follow-up was made 3 wk, 3 months and 1 yr after the event. 40 consecutive PUT
      subway drivers were followed. For each PUT driver, a control driver matched with
      regard to gender, age and country of birth was followed at identical intervals.
      MAIN RESULTS: the PUT group had significantly more sick days during the interval
      from the event to 3 wk later. During the period 3 wk to 3 months after the event
      no difference between the groups was observed. From 3 months to 1 yr after the
      PUT significantly more days were again reported by the PUT group. 38% in the PUT
      groups vs 14% in the control group had at least 1 month of sickness absence
      during this period. A mild acute psychophysiological reaction was observed 3 wk
      after the event, with elevated prolactin and increased sleep disturbance in the
      PUT group. Such acute reactions were transitory and not correlated with long-term
      sick leave, which was predicted independently, however, by a high plasma cortisol
      level (analysed in men) and a high depression score. Drivers in the group with
      seriously injured victims were absent from work for longer periods than drivers
      in the groups with mildly injured or dead victims. PUT victims described a
      successively worsened psychosocial work situation during the 12 months of follow
      up whereas the drivers in the control group described an unchanged situation.

PMID- 8153754
TI  - Psychotherapy for train drivers after railway suicide.
AB  - In Denmark there are approx. 50 railway suicides and suicide attempts each year.
      Most of these take place on urban railways such as the S-train in Copenhagen.
      There is a 1 in 8 chance that any one driver will be involved in such an incident
      each year. Since 1986 the Danske Statsbaner has implemented a policy aimed at
      minimising the negative psychological effects of railway suicides on train
      drivers. This case history describes how these procedures are put into effect.

PMID- 8153755
TI  - Mental first aid.
AB  - This paper reports a survey of staff of Oslo Sporveier who had been involved in
      serious incidents such as accidents resulting in severe personal injuries and
      death, suicide, robbery and assault. The survey was carried out to evaluate the
      efficacy of Mental First Aid in a retrospective study. The introduction of Mental
      First Aid was based on the beneficial effects from early intervention reported
      from follow-up studies after previous disasters, so for ethical reasons there was
      no control group. When help was given within the first few days without the use
      of any external specialists, and with strong support from colleagues during the
      first days back at work, there was little absenteeism. The beneficial effects of
      early intervention are stressed as is the use of non-professionals in forming a
      social network around employees who have been involved in traumatic incidents.
      Safety ombudsmen who have been given brief instruction are brought to the site of
      the incident to apply the principles of Mental First Aid. These secondary
      preventive measures are very effective and could be implemented by other medium
      sized transport companies whose staff are exposed to the risk of suicide
      attempts.

PMID- 8153756
TI  - A strategy for trauma debriefing after railway suicides.
AB  - Following an increase in the incidence of railway suicide from an average of four
      events a year up to 1989 to 12 in 1990 an initiative was developed between the
      District Department of Clinical and Community Psychology, Exeter Health Authority
      and British Rail, Western Region. Traincrew leaders and management had become
      increasingly aware of the severity of the short- and long-term effects on drivers
      of experiencing a suicide. Although a management strategy had been developed over
      time to deal with what had been a rare phenomenon it was clear that such a
      dramatic increase in suicides warranted a more professional approach to
      debriefing and trauma counselling. This paper describes the strategies adopted by
      psychologists in developing an understanding of the stresses of experiencing
      suicides and other major incidents. The outcome of small group sessions with
      affected drivers is outlined. An account of the strategy developed through
      workshops with traincrew leaders is detailed and a three-stage debriefing (shock,
      search, adjustment) and follow-up protocol is discussed. This process is proposed
      for adoption as normal procedure following suicides or similar traumas for
      drivers and line managers.

PMID- 8153757
TI  - The managerial nature of case management.
AB  - Case managers have been viewed as engaging in direct practice, community
      practice, or both. This article offers a third view: Case managers also engage in
      the practice of management. Employing Mintzberg's seminal research on chief
      executive behavior, the authors argue that case managers' work is similarly
      characterized by brevity, variety, and fragmentation. Case managers perform the
      10 roles developed in Mintzberg's original study. These roles are divided into
      three groups: interpersonal, including figurehead, leader, and liaison;
      informational, including monitor, disseminator, and spokesperson; and decision
      making, including entrepreneur, disturbance handler, resource allocator, and
      negotiator. Case managers' tasks associated with each role are presented.
      Considering their work as managerial in nature will help case managers more
      effectively assist clients in goal achievement.

PMID- 8153758
TI  - Grief: the unrecognized parental response to mental illness in a child.
AB  - The normal grief response of parents to the death of a child of any age is well
      documented in the literature. This response has some unique qualities because of
      the special nature of the parent-child relationship. Parents whose son or
      daughter develops a serious mental illness experience this same grief, but often
      it is not recognized or validated by society and either is not addressed by
      mental health professionals or is misperceived as evidence of pathology. As a
      result, healthy expression of parental grief over a child's mental illness is
      seriously inhibited, and problems, both for parents and the patient, are
      exacerbated. This article describes some common elements of parental bereavement,
      losses experienced with mental illness, the consequences of ignoring grief, and
      appropriate interventions for mental health professionals.

PMID- 8153759
TI  - Are the rights of people with mental illness still important?
AB  - This survey measured the attitudes of clinical social workers toward the rights
      of psychiatric patients who are involuntarily committed to institutions. The
      questions covered five content areas: involuntary commitment, environment and
      daily living, right to treatment, right to refuse treatment, and presumption of
      legal incompetence. Although the majority of respondents supported patients'
      rights, a minority demonstrated restrictive attitudes and an unawareness of
      existing laws regarding patients' rights. Controversial issues, such as the right
      to refuse treatment, evoked the least support.

PMID- 8153760
TI  - Bereavement services for families and peers of deceased residents of psychiatric
      institutions.
AB  - Families of patients who die while receiving care in an acute care setting face
      issues of loss and grief; other patients and staff members may also face these
      issues. Although informal bereavement services may exist in some settings, there
      often is no formally established bereavement service designed to assist surviving
      family members, patients, and staff members. Social work, with its concern for
      the social aspects of patients' lives, is the logical profession to provide
      leadership in establishing and providing formal bereavement assistance. The
      results of a literature search suggest that few such formalized services exist. A
      planned bereavement service may considerably lighten the burden for family
      survivors and for patients and staff, especially when the deceased has developed
      relationships within the acute care facility. An exemplar bereavement service is
      presented using data from the few existing or proposed efforts to formalize
      bereavement services in acute care settings.

PMID- 8153761
TI  - Consumer-centered social work practice: restoring client self-determination.
AB  - One of the highest traditional social work values is the maximization of client
      self-determination. In actual practice it is a difficult ethic to uphold,
      especially in this time of budget cuts and overwhelming caseloads. This article
      examines an orientation toward practice that places consumers at the center of
      decision making and control. The author examines current trends in the consumer
      movement, including advances among the aging, disabled, and mental health client
      populations. A comparison of medical-rehabilitation and independent living
      paradigms is presented to demonstrate fundamental philosophical differences. The
      author introduces suggestions to enhance participation by consumers for direct
      service workers, administrators and supervisors, and social work educators.

PMID- 8153762
TI  - Transitions in psychiatric inpatient clinical social work.
AB  - As a group, psychiatric inpatient clinical social workers have been dramatically
      affected by the economic crisis in mental health. As they have attempted to cope
      with a myriad of changes, they also have become leaders in bringing change about.
      This article described the transition process as experienced by 27 social workers
      who were interviewed in a descriptive exploratory study. The study showed that
      inpatient social workers are struggling to create ways to meet increased workload
      demands and are questioning the effectiveness of short-term hospital treatment.
      Respondents reported personal and professional losses as well as challenges. They
      expressed considerable concern about the future of their profession because of
      pressure to compromise standards.

PMID- 8153763
TI  - Dual relationships and professional boundaries.
AB  - Social workers enter into dual relationships when they engage in more than one
      relationship with a client, becoming social worker and friend, employer, teacher,
      business associate, or sex partner. This article reviews the research on dual
      relationships in the therapeutic professions and outlines the legal, ethical, and
      practice issues involved. The article defines dual relationships as boundary
      violations and provides a case example to show how even a posttermination
      friendship can be harmful to a client. Recommendations for preventing and
      responding to dual relationships are included.

PMID- 8153764
TI  - Childhood suicide and myths surrounding it.

PMID- 8153765
TI  - Dilemmas in the prophylaxis of Pneumocystis carinii pneumonia.
AB  - Pneumocystis carinii pneumonia has been the most common life-threatening
      opportunistic infection in patients with acquired immunodeficiency syndrome. With
      a better understanding of the natural history of HIV infection, however, we have
      come to realize that prophylaxis against P carinii can prevent the majority of
      such pneumonias. In this article, I focus on the rationale behind such
      prophylaxis, as well as the choices and dilemmas the clinician faces in deciding
      on the most appropriate therapy and when it should be instituted.

PMID- 8153766
TI  - Preoperative screening electrocardiography: predictive value for postoperative
      cardiac complications.
AB  - The purpose of this study was to evaluate the value of preoperative
      electrocardiography in predicting postoperative cardiac complications. Four
      hundred eighty-one patients having elective surgery were eligible. The patients'
      ages and specific ECG findings were recorded preoperatively. The patients had
      prospective follow-up from admission to discharge for the development of
      postoperative cardiac complications. The data were analyzed using stepwise
      logistic regression. Postoperative ischemic events were predicted by ECG findings
      of ST segment abnormalities and ECG evidence of previous myocardial infarction.
      Age, P wave abnormalities, and preoperative dysrhythmias were independent
      predictors of postoperative dysrhythmic events. These specific ECG findings may
      identify patients at risk of postoperative ischemia or dysrhythmia. These
      patients may benefit from aggressive preoperative cardiac evaluation or close
      postoperative cardiac monitoring.

PMID- 8153767
TI  - Physical activity patterns among adults in Georgia: results from the 1990
      Behavioral Risk Factor Surveillance System.
AB  - Regular physical activity increases a person's ability to perform daily
      activities more efficiently, reduces the risk of specific chronic diseases,
      including coronary artery disease, and lowers death rates in general. The Healthy
      People 2000 Physical Activity and Fitness Objectives underscored the importance
      of monitoring and tracking the prevalence of physical activity and fitness in the
      United States population for the purpose of planning, implementing, and
      evaluating efforts to improve the public's physical activity habits. This report
      examines the prevalence of self-reported leisure-time physical activity (LTPA)
      among southeastern adults aged 18 years and older living in the state of Georgia.
      Using data from the 1990 Behavioral Risk Factor Surveillance System (BRFSS)
      surveys from Georgia, we describe the LTPA patterns of Georgia adults aged 18
      years and older. A total of 1,723 adults were interviewed during 1990. Results
      show the following: women are less active than men, blacks are less active than
      whites, persons of lower socioeconomic status (SES) are less active than those of
      higher SES, and older adults are less active than younger adults. These results
      suggest that a more concerted effort needs to be made in promoting physical
      activity for women, persons of lower SES, and older adults.

PMID- 8153768
TI  - Birth defects surveillance: Jefferson County, Alabama, and Uppsala County,
      Sweden.
AB  - Birth defects in live-born infants were documented for 2 years in Jefferson
      County, Alabama (USA)--1986 and 1987--and in Uppsala County, Sweden--1985 and
      1986. A total of 27,561 live births (9,179 white male, 8,728 white female, 4,883
      black male, and 4,771 black female infants) occurred in Jefferson County; 6,896
      live births (3,535 male and 3,361 female) were recorded in Uppsala County. These
      newborns were studied to establish a database of birth defects for the two small
      geographic areas and to study similarities and differences. Rates of hip
      dislocation, heart malformations, and clubfoot were high in Swedish infants.
      Similar frequencies of spina bifida and polydactyly were noted in Alabama whites
      and Swedish infants. Regional registries offer a systematic approach to detection
      of clustering of specific birth defects, identification of families for further
      study, location of patients with unique needs, and enhanced coordination of
      health services, including genetic counseling.

PMID- 8153769
TI  - Follow-up survey of inpatients with AIDS and HIV infection: economic impact on
      hospitals in North Carolina.
AB  - This study is a 2-year follow-up to a 1987-1988 survey of North Carolina
      hospitals regarding hospital utilization by patients with acquired
      immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV)
      infection. Almost 99% of the state's hospitals participated in the re-survey for
      the fiscal year 1989-1990. The number of general hospitals treating these
      patients grew by 57%; HIV/AIDS inpatients increased by 189% from 540 to 1,561.
      Total general hospital charges for HIV/AIDS inpatients increased from $7,685,000
      to $26,957,000, an increase of 251%. Of these charges the amount that was
      uncompensated by insurance increased by 293% to $7,733,000. Fifteen large
      tertiary general hospitals treated 80% of the HIV/AIDS inpatients and accounted
      for $6,093,000 (79%) of the uncompensated charges related to these patients.

PMID- 8153770
TI  - Establishing an internal medicine practice: a model to determine economic
      feasibility.
AB  - To make informed career decisions, physicians must acquire a basic knowledge in
      medical management and health care economics as they evaluate the potential
      survival and growth of a primary care practice. Health care providers considering
      a specific community and local leaders and hospital administrators attempting to
      recruit internal medicine physicians need a method by which they can evaluate a
      community's potential for supporting a first or additional primary care
      physician. To develop this method, we conducted a detailed survey of
      nonmetropolitan internal medicine generalists and primary care physicians. Data
      collected from internal medicine physicians and their administrative staff
      reflected the volume of ambulatory and hospital visits and the direct and
      indirect costs of the practice over the previous 24 months. Using the fixed and
      operating cost data, as well as number of patient visits and patient care
      revenue, we designed a model to project the economic feasibility of establishing
      an internal medicine practice in a specific community. This model can be used to
      project the number of adult primary care visits a community can generate for a
      prospective physician, as well as to estimate the direct and indirect costs,
      annualized capital costs, gross revenue, and net income of the practice.

PMID- 8153771
TI  - Randomized study of cefotaxime versus ceftriaxone for uncomplicated gonorrhea.
AB  - Cefotaxime is a third-generation cephalosporin with excellent in vitro
      antimicrobial activity against Neisseria gonorrhoeae, including beta-lactamase
      producing strains. A single 1-g intramuscular dose is suitable for the treatment
      of uncomplicated gonorrhea. We conducted an open, randomized study to evaluate
      the efficacy, safety, and cost impact of a lower dose (500 mg) of cefotaxime
      versus 250 mg ceftriaxone, an often recommended treatment for uncomplicated
      gonorrhea. Of the 222 patients enrolled, the cases of 151 were fully assessable.
      Bacteriologic elimination rates were 99% in the cefotaxime group and 100% in the
      ceftriaxone group. Clinical response rates were 78% and 83% in the two groups,
      respectively. Adverse clinical events occurred in 4% and 9% of patients in the
      two groups, respectively. The average wholesale price of 500 mg cefotaxime is 31%
      lower than that of 250 mg ceftriaxone. A 500-mg dose of cefotaxime appears to be
      a safe and cost-effective alternative to 250 mg ceftriaxone for the treatment of
      uncomplicated gonorrhea.

PMID- 8153772
TI  - Alpha-delta sleep in patients with a chief complaint of chronic fatigue.
AB  - Our prospective, standardized cohort study was designed to assess the presence of
      alpha wave intrusions during non-rapid eye movement sleep (alpha-delta sleep) and
      its relationship to fibromyalgia, major depression, and chronic fatigue syndrome
      (CFS) in patients with a chief complaint of chronic fatigue. The study group
      comprised 30 consecutive patients seen at a university hospital referral clinic
      for evaluation of chronic fatigue. All patients had nocturnal polysomnography,
      dolorimetric tender point assessment for fibromyalgia, a comprehensive history,
      physical, and laboratory evaluation, and a structured psychiatric interview.
      Alpha-delta sleep was identified in 8 of the 30 patients (26%), major depression
      in 20 (67%), CFS in 15 (50%), and fibromyalgia in 4 (13%). Ten of the 30 patients
      (33%) had a primary sleep disorder (sleep apnea, periodic limb movements, or
      narcolepsy). Alpha-delta sleep was not significantly correlated with
      fibromyalgia, CFS, major depression, or primary sleep disorders, but was
      significantly more common among patients who had chronic fatigue without major
      depression. We conclude that primary sleep disorders are relatively common among
      patients with chronic fatigue and must be diligently sought and treated. Alpha
      delta sleep is not a marker of fibromyalgia or CFS, but may contribute to the
      illness of nondepressed patients with these conditions.

PMID- 8153773
TI  - Mirizzi's syndrome.
AB  - Mirizzi's syndrome is a partial obstruction of the biliary tree caused by a stone
      impacted in the cystic duct, with or without development of a cholecysto-biliary
      fistula. We report our experience with five cases and review current methods of
      diagnosis and management. Preoperative diagnosis greatly facilitates management.
      Diagnosis may require a combination of ultrasonography, computed tomography, and
      cholangiography (percutaneous or endoscopic retrograde). At surgery, dissection
      in the triangle of Calot should be minimized to avoid injury to the common bile
      duct. Often, a partial cholecystectomy is the only safe option. Defects in the
      common bile duct can be repaired by a variety of methods. The morbidity and
      mortality associated with this rare syndrome can be relatively high. A number of
      patients may have late biliary strictures.

PMID- 8153774
TI  - Histoplasmosis during childhood.
AB  - To define the clinical presentation of histoplasmosis among hospitalized
      children, we reviewed the charts of patients treated for histoplasmosis at
      Vanderbilt University Children's Hospital during the years 1968 through 1988.
      Thirty-five patients with histoplasmosis diagnosed by culture, pathologic
      examination, or serologic testing were identified, including 29 patients (83%)
      with pulmonary/mediastinal infection, 5 (14%) with disseminated disease, and 1
      (3%) with primary cutaneous histoplasmosis. The most common symptoms included
      fever, present in 26 patients (74%), and cough, present in 20 (57%). Of 26
      patients with fever, 18 (69%) had fever of > 2 weeks' duration and 7 (27%) had
      temperatures > or = 40.5 degrees C (> or = 105 degrees F). Abnormal physical
      findings were few, but 19 patients (54%) had wheezing. Chest radiographs were
      obtained in all cases except one; 31 (91%) showed abnormalities, including
      adenopathy in 25 cases (74%) and infiltrates in 19 (56%). Histoplasmin skin tests
      were positive for 22 (96%) of the 23 patients tested. No cases of classic
      disseminated histoplasmosis of infancy were identified. Histoplasmosis should be
      considered in the differential diagnosis when children living in endemic areas
      are evaluated for persistent fever, cough, and/or wheezing, particularly if
      adenopathy is seen on the chest radiograph.

PMID- 8153775
TI  - Hospital-acquired infections in pediatric burn patients.
AB  - To determine the epidemiologic characteristics of hospital-acquired infections
      (HAI) in pediatric burn patients, we retrospectively reviewed hospital charts of
      pediatric burn patients from two similar burn units. All patients less than 18
      years of age admitted to the burn unit from January 1, 1980 to July 10, 1988,
      were enrolled. Charts were analyzed for age, sex, burn injury (type, depth, burn
      surface area), and hospital course (burn wound therapy, use of indwelling
      catheters or tubes, infectious complications, antibiotic use, cause of death if
      patient died). Statistical analysis was done using a logistic regression model.
      Of the 224 children admitted, 32 (14%) had 58 infections during their stay in the
      burn unit. There was no significant difference in age, sex, race, burn type or
      use of wound excision between patients with or without infection. Patients who
      acquired an infection were more likely to have sustained a > or = 20% full
      thickness burn (14/32 vs 3/192 without infection), a smoke inhalation injury
      (10/32 vs 8/192), or have an indwelling device (29/32 vs 77/192). Thirteen (22%)
      of the 58 infections were burn wound infections due to Staphylococcus aureus or
      Pseudomonas aeruginosa, 12 (21%) were urinary tract infections due to
      Enterobacteriaceae, 11 (19%) were pneumonias caused by S aureus, Streptococcus
      pneumoniae or Pseudomonas sp, and 10 (17%) were bacteremias caused by S aureus or
      coagulase-negative staphylococci. The infection rate in pediatric patients
      hospitalized for burn injury in our study was significantly lower than the
      infection rate described for adult burn patients. As in adult patients, burn
      wound infections, pulmonary infections, and catheter-associated bacteremias are
      the most common infections in burned children. However, urinary tract infections
      are more frequent in the pediatric population. Risk factors (> or = 20% full
      thickness burns, indwelling devices) and causative organisms are similar in both
      age groups.

PMID- 8153776
TI  - Atypical cat-scratch disease: diagnosis by a serologic test for Rochalimaea
      species.
AB  - Three patients with atypical manifestations of cat-scratch disease (CSD) had the
      diagnosis supported by a newly available serologic assay for antibodies to
      Rochalimaea henselae. Previously, CSD has been a diagnosis of exclusion because
      no confirmatory test was readily available. Atypical or severe cases of CSD have
      often required detailed (and expensive) clinical and laboratory investigation.
      The use of Rochalimaea-specific serologic tests may help avoid extensive
      diagnostic testing or invasive procedures in such cases.

PMID- 8153777
TI  - Gastrostomy: evaluation of a new tube using an old technique.
AB  - Formerly, for gastrostomy, we passed a No. 18 French red rubber catheter through
      the antrum of the stomach with the tip directed toward the fundus. We used this
      method with great success, both for decompression and feeding. Recently, a tube
      made of silicone rubber and thus resistant to gastric secretions was manufactured
      for us by the Medical Innovations Corporation of Milpitas, Calif. The tip of the
      tube is long enough to reach to within 3 cm of the fundus. A doughnut-shaped
      inflatable balloon fits nicely against the gastric mucosa, and a "Secur-Lok" ring
      external to the abdominal wall slides down to the skin, allowing the tube to be
      held in position without the use of sutures. We believe that the tube placed
      using the above technique is effective, comfortable, and reliable. This study was
      done to evaluate its efficacy. We report a series of 90 patients in whom this new
      gastrostomy tube was placed. We discuss the lasting qualities of the tube, the
      function of the doughnut-shaped balloon, the hypothesis we have developed to
      explain why there has been no esophageal reflux with this tube, and the efficacy
      of the Secur-Lok ring in holding the tube in position without the use of sutures.

PMID- 8153778
TI  - Outbreaks of syphilis in rural Texas towns, 1991-1992.
AB  - Between 1986 and 1990, rates of primary and secondary syphilis increased 134% in
      rural counties in the South. Reasons for the increases are speculative. During
      the 14 months ending in October 1992, outbreaks in four eastern Texas counties
      provided an opportunity to characterize syphilis in rural Texas. We reviewed
      records for 118 patients and 339 sex partners. Three outbreaks were concentrated
      in neighborhoods where crack cocaine dealers conducted business and exchange of
      sex for drugs or money was common; the fourth outbreak involved out-of-town
      prostitutes who visited undocumented alien workers. Among the 118 syphilis cases,
      15 (13%) were primary, 35 (30%) were secondary. Most patients were black (105,
      89%); the male-female ratio was 1:1. One woman gave birth to an infant with
      congenital syphilis. Almost half of the sex partners were infected. HIV pretest
      counseling was completed for only 55 patients (47%), and only 23 (19%) were
      tested for the human immunodeficiency virus. These four rural outbreaks of
      syphilis associated with crack cocaine and the exchange of sex for drugs or money
      mirror recent urban syphilis outbreaks. Patients in these rural syphilis
      outbreaks are at risk for HIV infection, but HIV testing has not been emphasized
      by public health workers.

PMID- 8153779
TI  - Importance of designated thoracic trauma surgeons in the management of traumatic
      aortic transection.
AB  - The medical literature is replete with reports on traumatic aortic transection.
      These reports have delineated many factors regarding the morbidity and high
      mortality of this ominous injury. Most reports are reviews of the collective
      experience of a single institution over a period of years. It is likely that many
      authors writing on the subject of traumatic aortic transection have no experience
      with operative repair of the lesion. There has been debate about the various
      techniques of primary repair versus graft insertion, as well as the question of
      whether cardiopulmonary bypass is superior to the "clamp and sew" methods. No
      studies have directly examined the skills of individual surgeons with respect to
      outcome. We present the results of a study from a university-affiliated level I
      trauma center in which the outcomes from various groups of surgeons were compared
      over a 5-year period. The information in this study strongly suggests that
      designated thoracic trauma surgeons who are promptly available and have dedicated
      interests in trauma patients achieve better results.

PMID- 8153780
TI  - Postoperative analgesia after major shoulder surgery with interscalene brachial
      plexus blockade: etidocaine versus bupivacaine.
AB  - Postoperative pain is commonly treated with significant doses of narcotics,
      occasionally resulting in side effects including nausea, pruritus, and
      respiratory depression. One potential advantage of regional anesthesia is
      profound postoperative analgesia that reduces exposure to potent narcotics. To
      evaluate the efficacy of two long-acting local anesthetics, bupivacaine and
      etidocaine, in providing pain relief after major shoulder surgery, we randomized
      20 patients to receive either bupivacaine or etidocaine for brachial plexus block
      as the primary anesthetic for shoulder surgery. Surgeons, patients, and the acute
      pain service were blinded as to drug selection. After the patient was sedated, an
      interscalene block was placed with the use of a nerve stimulator to facilitate
      proper needle placement. Forty milliliters of either 0.5% bupivacaine or 0.75%
      etidocaine containing 5 micrograms/mL epinephrine was injected into the brachial
      plexus sheath. An additional 8 mL of local anesthetic was administered for
      superficial cervical plexus blockade. Intraoperative sedation was accomplished
      with an intravenous infusion of methohexital as needed. After surgery, patients
      received a standard patient-controlled analgesia protocol providing incremental
      doses of morphine. The degree of postoperative analgesia resulting from residual
      local anesthetic effect was expressed as the time until first morphine
      requirement and the total dose of morphine required during the first 24 hours
      postoperatively. We found no statistically significant intergroup differences
      either in time of initial use of morphine or in the total dose of morphine
      required in the first 24 hours. Both etidocaine and bupivacaine provide prolonged
      analgesia after major shoulder surgery when injected into the brachial plexus.
      Bupivacaine, however, possesses significant cardiotoxicity and has a relatively
      delayed onset in peripheral neural blockade. Etidocaine is less cardiotoxic and
      also has a more rapid onset of effect. Thus etidocaine may be a preferable agent
      for interscalene block for major shoulder surgery.

PMID- 8153781
TI  - Comparison of oral ketorolac, intramuscular morphine, and placebo for treatment
      of pain after orthopedic surgery.
AB  - Using a randomized, double-blind, placebo-controlled, parallel, single-dose,
      single-center, 6-hour study, we compared the analgesic response and tolerability
      of oral ketorolac tromethamine and intramuscular morphine sulfate and placebo.
      The study group comprised 176 patients with moderate, severe, or very severe pain
      after hip or knee surgery at a teaching hospital. Patients received either 10 mg
      of ketorolac orally, 10 mg of morphine intramuscularly, 5 mg of morphine IM, or
      placebo. Patients rated pain intensity at baseline and pain intensity and pain
      relief at 30 minutes, 1 hour, and hourly thereafter for 6 hours. At study
      completion, we evaluated overall patient ratings of pain relief and occurrence of
      adverse events. Summed pain intensity difference scores and total pain relief
      scores showed the active medications to be significantly superior to placebo and
      not significantly different from each other. The 10-mg dose of morphine showed a
      small advantage over ketorolac in peak analgesic effect, but the onset of pain
      relief was comparable among the active agents. The incidence of adverse events
      among the active-treatment groups was similar, though there was a numerical trend
      favoring ketorolac over 10 mg of morphine. We found oral ketorolac to be an
      effective alternative to parenteral opioids for the treatment of pain after hip
      or knee surgery in patients who can tolerate oral medication.

PMID- 8153782
TI  - Episiotomy repair: chromic versus polyglycolic acid suture.
AB  - The use of an episiotomy for vaginal delivery is a controversial topic in modern
      obstetrics. If one is done, however, correct technique and appropriate suture
      material are important. On the LSU Obstetrics Service, the usual midline
      episiotomy has traditionally been closed with 2-0 chromic suture. Theoretically,
      the use of a less reactive material, eg, polyglycolic acid (Dexon), may be
      beneficial in terms of acute postpartum discomfort and healing. As a comparison
      of healing and patient comfort parameters between 2-0 chromic and 2-0
      polyglycolic acid suture used for episiotomy repair after delivery, two
      consecutive months' worth of parturients at Medical Center of Louisiana/Charity
      Hospital had episiotomy repair, with either chromic or polyglycolic acid suture,
      by junior house officers routinely attending delivery. Patients had follow-up
      during hospital stay, and when examined at 6 weeks for evidence of suture line
      healing, they were also asked about comfort and resumption of sexual activity. Of
      48 patients who had repair with 2-0 chromic suture, 6 were lost to follow-up. Of
      44 gravidas who had repair with 2-0 polyglycolic acid suture, 7 were lost to
      follow-up. At the 6-week postpartum examination, patients with polyglycolic acid
      sutures had significantly better healing. A noticeable scar was present in 42 of
      42 patients with chromic sutures versus 21 of 37 in the polyglycolic acid group,
      a scar with granulation tissue in 16 of 42 versus 3 of 37, and a gaping scar in 9
      of 42 and 0 of 37, respectively. Recovery of function, measured by resumption of
      sexual activity by 6 weeks, was demonstrated in 1 of 42 patients who had chromic
      sutures versus 19 of 37 patients who had polyglycolic acid sutures. Episiotomy
      repair with 2-0 polyglycolic acid (Dexon) offers significant advantages over
      traditional 2-0 chromic suture, both in terms of wound healing and resumption of
      normal patient activity, including sexual activity.

PMID- 8153783
TI  - Accuracy of pulse oximetry during hypoxemia.
AB  - To determine the accuracy of four pulse oximeters during mild and moderate
      arterial hypoxemia, we produced stepwise arterial blood desaturation in 25
      healthy, nonsmoking volunteers by adjusting the inhaled oxygen concentration. At
      plateaus of < 80%, 85% to 90%, 90% to 95%, and 95% to 100%, pulse oximetry
      saturation (SpO2) was measured with the four different monitors: Dinamap Plus
      Model 8700, Oxyshuttle, Ohmeda 3700, and MiniOx IV. Arterial blood samples were
      analyzed with a co-oximeter and the arterial oxyhemoglobin saturation (SaO2) was
      compared with the SpO2 readings at each plateau. Significant deterioration in the
      accuracy of pulse oximeters was observed as SaO2 decreased. In 14 instances of
      hypoxemia (SaO2 < 90%), subjects exhibited SpO2 values greater than 90%. In
      conclusion, the accuracy of pulse oximetry deteriorates as hypoxemia worsens.
      Confirmation of arterial blood oxyhemoglobin saturation by co-oximetry is
      necessary when precise determination of arterial oxyhemoglobin level is critical.

PMID- 8153784
TI  - Sinusitis in bone marrow transplantation.
AB  - Bone marrow transplantation has become a beneficial and curative technique used
      in treatment of patients with different hematologic conditions. It has become
      widely used at our institution for hematologic malignancies and certain resistant
      solid tumors. However, this treatment can result in immunosuppression, with an
      increased chance of infection. The purpose of this study was to review the causes
      of infections and determine the number of patients diagnosed with sinusitis. In
      the retrospective study, we evaluated the cases of bone marrow transplant
      patients for incidence and cause of fever. Sixty-eight percent of patients had
      fever after transplant; of these, 59% had fever of unknown origin. Only 1% of the
      patients with fever were diagnosed with sinusitis. In the evaluation of fever,
      sinusitis was not usually suspected and therefore was not included in the
      differential diagnosis. With such a high percentage of fever of unknown origin in
      this growing patient population, appropriate pretreatment evaluation of each case
      to rule out sinusitis should be considered.

PMID- 8153785
TI  - Hypereosinophilic syndrome associated with HIV infection. Military Medical
      Consortium for Applied Retroviral Research.
AB  - A hypereosinophilic syndrome associated with dermatitis has been observed rarely
      in association with HIV infection. We describe the case of a young man with AIDS
      who came to us with a diffuse cutaneous eruption, fever, angioedema,
      eosinophilia, and a mildly elevated serum IgE level. No allergic or infectious
      cause of this illness could be determined, and the patient was treated with
      corticosteroids and PUVA therapy, resulting in complete resolution of the
      dermatitis and associated findings. In this case, there were clinical and
      histopathologic similarities to the idiopathic hypereosinophilic syndrome and to
      acute graft-versus-host disease. The serum level of the cytokine interleukin-5
      (IL-5), which is associated with eosinophil production, was found to be mildly
      elevated during the peak of the eruption, while samples drawn previously and
      subsequently were not. Although it appears that the syndrome we describe is
      associated with the measurably elevated level of IL-5, further investigation is
      required to determine whether there is a cause and effect relationship between IL
      5 and this entity. A brief review of the literature concerning eosinophils and
      HIV infection is also presented in the context of this case.

PMID- 8153786
TI  - Splenic infection simulating lymphoma: an unusual presentation of disseminated
      Pneumocystis carinii infection.
AB  - This report of disseminated pneumocystosis in an HIV-infected patient describes
      an unusual presentation consisting of splenic disease mimicking lymphoma, absence
      of typical roentgenographic signs of pulmonary or disseminated pneumocystis, and
      absence of use of aerosolized pentamidine. Because of these factors, a diagnosis
      of disseminated pneumocystosis was not considered. Our case in combination with
      other recent reports emphasizes the need to consider disseminated pneumocystosis
      in HIV-infected patients, even if they have no obvious pulmonary disease and have
      not received aerosolized pentamidine therapy. Timely recognition of this lethal
      infection is important for initiation of potentially curative therapy.

PMID- 8153787
TI  - Disseminated cryptococcal disease complicating steroid therapy for Pneumocystis
      carinii pneumonia in a patient with AIDS.
AB  - Recent studies have suggested that steroid therapy may reduce the morbidity and
      mortality of HIV-associated Pneumocystis carinii pneumonia (PCP) in a select
      population of patients. However, the risks of steroid therapy for this group have
      not been well defined. We describe the case of a patient admitted with severe PCP
      whose treatment included high-dose steroids. During his hospitalization,
      overwhelming cryptococcal disease developed, contributing to his death. We
      postulate that the rapidity of progression was due, in part, to the steroid
      therapy. We have also reviewed the literature. We recommend screening for
      cryptococcal infection before beginning steroid therapy.

PMID- 8153788
TI  - Endometriosis manifesting as a urachal tumor.
AB  - Endometriosis of abdominal wall scars is rare, especially in the postmenopausal
      woman. However, it must be considered as a possible cause of any abdominal wall
      mass in a woman who has had previous pelvic surgery and who is of reproductive
      age or taking exogenous hormones.

PMID- 8153789
TI  - Moraxella catarrhalis bacteremia and preseptal cellulitis.
AB  - Invasive disease due to Moraxella catarrhalis is rare and has been associated
      mostly with immune deficiency conditions. We describe the first case of M
      catarrhalis bacteremia and preseptal cellulitis in an immunocompetent infant.
      This organism may be evolving from one with low pathogenicity to one with
      increased pathogenicity.

PMID- 8153790
TI  - Cashew nut dermatitis.
AB  - The urushiol dermatitis caused by plants of the Anacardiaceae family is the most
      common cause of acute allergic contact dermatitis. We have reported a case of
      cashew nut urushiol dermatitis due to ingestion of homemade cashew nut butter
      contaminated by cashew nut shell oil. With the precautions taken today to avoid
      contamination of food products with cashew urushiols, it is rare to find a case
      of cashew nut dermatitis in the United States. We have found no other report of
      contact dermatitis due to cashew nut butter. Moreover, though hinted at in the
      literature, there has been no previous detailed report of perianal contact
      dermatitis due to cashew ingestion. The fact that our patient was ill enough to
      require treatment with 3 weeks of systemic steroid therapy highlights the
      potential public health hazard of consumption of improperly prepared cashew
      products. However, the risk of cashew nut dermatitis today remains small, and
      this should not discourage cashew lovers from enjoying their treats. A final
      lesson to be learned from this case is that perianal eruptions may be due to
      materials deliberately applied to the anogenital region or to ingested antigens
      that remain sufficiently intact within the feces to affect perianal skin.

PMID- 8153791
TI  - Drug-induced ileal disease: a new entity in the differential diagnosis of Crohn's
      disease.
AB  - Ileal disease in the United States is usually caused by Crohn's disease.
      Accumulating reports, however, show that nonsteroidal anti-inflammatory drugs
      (NSAIDs) may cause ileal and colonic inflammation and strictures that may mimic
      inflammatory bowel disease and other conditions. A patient is described with
      weight loss, loose stools, and terminal ileal disease, all of which resolved
      after discontinuing an NSAID. Clinicians must become familiar with the expanding
      clinical and radiological spectrum of NSAID gastrointestinal tract toxicity.

PMID- 8153792
TI  - Culture-positive cytomegalovirus pleuritis in a nonimmunocompromised host.

PMID- 8153793
TI  - The infra-aortic arteries of the spine: their variability and clinical
      significance.
AB  - The infra-aortic spinal arteries caudal to the aortic bifurcation were studied in
      20 perinatal and adult cadavers to determine their import relative to
      extraforaminal approaches to the lower lumbar discs as well as their probable
      involvement in certain cases of radiculomedullary ischemia. Analysis of these
      specimens indicated that, despite considerable variation, the arteries to the L4
      L5 and L5-S1 intervertebral foramens generally were not related to the disc
      dorsolateral zones where lateral surgical approaches are best accomplished. Also,
      the frequency in which the fourth as well as the fifth lumbar and all sacral
      segmental vessels were dependent on the posterior division of the hypogastric
      artery may help explain how spinal cord ischemia could occur in individuals with
      vulnerable cord vascular patterns and/or spinal arteriopathy after interruption
      of hypogastric artery blood flow during pelvic operations.

PMID- 8153794
TI  - A preoperative and postoperative study of the accuracy and value of
      electrodiagnosis in patients with lumbosacral disc herniation.

PMID- 8153795
TI  - A prospective, randomized study of lumbar fusion: preliminary results.

PMID- 8153796
TI  - Patient outcomes after lumbar spinal fusions. North American Spine Society Ad Hoc
      Committee on Spinal Fusion.

PMID- 8153797
TI  - Spina bifida occulta of S1 is not an innocent finding.
AB  - One thousand two hundred patients (600 women and 600 men) aged 18 to 72 years
      were referred for computed tomographic examination of the lumbosacral spine (L3
      S1) after low-back pain or sciatica. Patients with spinal abnormalities other
      than spina bifida occulta (SBO)-S1 and findings other than posterior herniation
      of intervertebral disc were not included in this study. All of the patients
      underwent conventional radiographs of the lumbosacral spine. The incidence of SBO
      S1 was higher in younger age groups and decreased with age. Patients with SBO-S1
      showed a higher incidence of posterior disc herniation, which increased with age.
      This can be explained by instability of the base of the lumbar spine caused by
      SBO-S1, which produces a predisposition to posterior disc herniation. The results
      were statistically significant.

PMID- 8153798
TI  - Nystagmus and joint position sensation: their importance in posterior
      occipitocervical fusion in rheumatoid arthritis.
AB  - It is widely believed that brain stem dysfunction and cranial nerve palsies in
      patients with rheumatoid arthritis (RA) are common and related to the vertical
      translocation of the odontoid process. In our database of 235 patients with
      seropositive RA and craniocervical junction involvement, we have found a very low
      incidence of such problems. Long tract signs were common, but loss of
      proprioception (joint position sensation) as the sole neurologic deficit was
      rare. Nystagmus was found to be associated with the tonsillar herniation of a
      Chiari 1 malformation and loss of joint position sensation with severe
      compression of the posterior aspect of the spinal cord at the craniocervical
      junction. The implications for posterior occipitocervical fusion, particularly by
      sublaminar wiring, are discussed.

PMID- 8153799
TI  - Neuroradiologic and electrophysiologic assessment of cervical spondylotic
      amyotrophy.
AB  - Dissociated motor loss due to cervical spondylosis and disc herniation was
      evaluated in 10 patients who presented with left deltoid paresis in the absence
      of sensory deficits or myelopathy. All of these cases underwent cervical anterior
      decompression. Based on magnetic resonance imaging, computed tomography
      myelography, and computed tomography discography, patients were divided into two
      pathologic types: The first showed focal bony spur and disc herniation with axial
      cord rotation and nerve root compression, and the second demonstrated ventral
      cord flattening. Electrophysiologic studies included evoked spinal potentials,
      motor evoked potentials, and evoked muscle action potentials. Motor evoked
      potentials, recorded epidurally from the ventral aspect of the thecal sac and the
      nerve root within the anterior discectomy or vertebrectomy sites, proved
      clinically most useful. Combining the latest available neuroradiologic and
      electrophysiologic information, 4 types of neural injury associated with deltoid
      pareses were identified in the 10 patients. The first included isolated C5 nerve
      root lesions; the second, C6 nerve root lesions; the third, both C5 and C6 nerve
      root lesions, and finally, intrinsic cord pathology.

PMID- 8153800
TI  - Noninvasive discrimination of brachial plexus involvement in upper limb pain.
AB  - The ability of Elvey's "brachial plexus tension test" to identify pain referred
      from the cervical region was investigated in 50 patients with unilateral shoulder
      and upper arm pain: 25 reported symptoms commencing after open heart surgery,
      indicating a high probability of referred pain due to that procedure; 25 were
      athletes with injuries from throwing movements, a cause appearing much less
      likely to cause referred pain. Twenty-five asymptomatic subjects with no history
      of spinal or limb pain also were tested. Cervical and upper limb maneuvers of the
      test were assessed goniometrically. The cardiac group showed significantly
      greater test results than those of the other groups, suggesting that the test is
      able to discriminate referred and local sources of upper limb pain.

PMID- 8153801
TI  - Intraoperative ultrasonographic evaluation of the spinal cord in cervical
      myelopathy.
AB  - Intraoperative spinal ultrasonography (IOSS) was used to evaluate and monitor the
      spinal cord in 49 patients with cervical myelopathy. Intraoperative spinal
      ultrasonography demonstrated movements of the dura mater and the spinal cord at
      the cardiac rate, with some variability in intensity and mode. It also delineated
      the anterior surface of the spinal canal and configuration of the spinal cord.
      Statistical analysis showed no correlation between clinical outcome and
      morphologic restoration, and between clinical outcome and variations in intensity
      or mode of the pulsatile spinal cord movements. Spinal cord motions were surmised
      to be generated not only by the anterior spinal artery, but also by other
      factors. Dural pulsations clearly did not always imply the absence of compression
      of the spinal cord. Intraoperative spinal ultrasonography was thus quite useful
      for monitoring decompression in cervical myelopathy.

PMID- 8153802
TI  - On the utility of the SCL-90-R with low-back pain patients.
AB  - The SCL-90-R has become an increasingly popular measure of maladjustment. Its use
      beyond simply screening chronic low-back pain (CLBP) patients has been
      criticized, however, in part, because it appears to be a single-factor
      instrument. In fact, its nine major scales do share only one important common
      factor, i.e., general psychological discomfort. The scale most applicable to
      CLBP, however, somatization (SOM), has sufficient specific variance that it does
      not simply measure discomfort and predicts several other measures better than the
      SCL-90-Rs more reliable composite measure (GSI). Using SOM in conjunction with
      the GSI to separate psychological from physical discomfort is therefore both
      clinically and psychometrically appropriate. Other objections to the test are
      critically evaluated. The potential clinical relevance of the SCL-90-R is
      discussed.

PMID- 8153803
TI  - Objective assessment for exercise treatment on the B-200 isostation as part of
      work tolerance rehabilitation. A random prospective blind evaluation with
      comparison control population.
AB  - The purpose of this study was to assess repeated exercise on the B-200 Isostation
      as part of rehabilitation work tolerance for nonsurgical patients with lumbar
      spine disorders. For a consecutive 7-month period, treatment subjects were
      randomly assigned according to birth date for participation in two groups: a
      standard work tolerance program only or standard work tolerance program plus
      inclusion of exercise on the B-200 Isostation. Each patient had similar referral
      diagnosis requiring conservative treatment. Treatment groups were compared with a
      control population of volunteers who had neither back pain nor known underlying
      spinal pathology. All study patients had objective measurement of range of
      motion, isometric strength, and velocity of motion, on the B-200 Isostation
      before treatment and at follow-up 3 weeks after treatment. The data showed no
      significant difference of percent improvement when comparing patients in either
      of the randomized assigned treatment groups. There was a higher percentage of
      improvement for each treatment group as compared with the control individuals,
      however. Based on our study using the B-200 Isostation, there is little objective
      justification for including exercise on the B-200 dynametric Isostation as part
      of the rehabilitation routine for improvement of functional physical capacity.

PMID- 8153804
TI  - Laser discectomy: a review.
AB  - The percutaneous treatment of lumbar disc disease with laser energy has emerged
      recently as an alternative to open surgical or even mechanical percutaneous
      methods. Although numerous laser wavelengths have been employed in both the
      experimental and clinical settings, no consensus exists regarding selection of
      laser, treatment duration, or energy requirements. Inspection of the disc/water
      absorption spectrum combined with the limitations of the fiberoptic delivery
      systems argue for the use of lasers near 2.0 microns, such as the 2.1-microns
      Ho:YAG. Although recently developed in vitro models have allowed for laser system
      comparisons, most clinical work has been empiric, uncontrolled, and in very small
      series.

PMID- 8153805
TI  - Pedicle screw placement with intraosseous endoscopy.
AB  - This study was undertaken to evaluate the efficiency of intraosseous endoscopy
      for the insertion of pedicle screws. Adult sheep served as an animal model. Under
      general anesthesia, the authors exposed the posterior lumbar elements through a
      midline spinal approach and cannulated six to eight pedicles in each sheep,
      without the use of radiographic or fluoroscopic guidance. Placement of properly
      located holes as well as intentionally misdirected holes was attempted. Using the
      fiber optic endoscope, direct examination of the interior of 22 pedicle screw
      holes was performed. Nine deliberate and 2 unintentional perforations, for a
      total of 11 defects in 22 pedicles, were easily recognized. These were confirmed
      by gross examination after specimens were harvested. Defects as small as 2 mm in
      diameter, not detected on palpation with a standard probe, were able to be
      closely inspected. The use of intraosseous endoscopy may serve as a useful
      adjunct in the placement of pedicle screws.

PMID- 8153806
TI  - Anatomic and radiographic study of dorsal root ganglia.
AB  - Anatomic and radiographic studies were made to investigate normal variation of
      dorsal root ganglia in lumbosacral roots. The spinal nerves could be divided into
      two groups, with and without bifurcation of ventral nerve root and dorsal root
      ganglion. The bifurcated group was further classified into three types. L4 and L5
      nerve roots were all bifurcated, and S1 were all nonbifurcated. The positions of
      dorsal root ganglia were classified into three types: intraspinal,
      intraforaminal, and extraforaminal. At L4 and L5 nerve roots, they were mostly
      intraforaminal, whereas at S1, they were mostly intraspinal. Proximally placed
      ganglia had a high frequency of ganglionic indentation. The incidence of
      intraspinal dorsal root ganglia was much higher clinically than in anatomic
      studies. Variations in connecting patterns or positions of dorsal root ganglia
      may be related to the occurrence and variety of radicular symptoms. The dorsal
      root ganglia is clinically important, and its location may correspond to clinical
      symptoms.

PMID- 8153807
TI  - Midline fascial splitting approach to the iliac crest for bone graft. A new
      approach.
AB  - The midline fascial splitting approach is a modified midline approach to the
      iliac crest for bone graft that takes advantage of the anatomic planes between
      layers of the dorsal lumbar fascia. Two hundred consecutive grafts were taken by
      this technique with one superficial infection, two cases of serous hematoma, and
      three patients with significant postoperative pain at the harvest site, for an
      overall complication rate of 3%. In comparison, bone grafts were harvested from
      200 consecutive patients by the midline subcutaneous approach to the iliac crest
      with 2 deep infections, 1 cluneal nerve injury, 15 patients with severe and
      disabling pain at the harvest site, and 12 patients with a serous hematoma, for
      an overall complication rate of 15%. The midline fascial splitting approach
      significantly reduced the incidence of postoperative serous hematoma (P < 0.007)
      as well as the incidence of significant and disabling pain (P < 0.001). In
      addition, the approach is simple, straightforward, anatomic, and decreases trauma
      to soft tissues.

PMID- 8153808
TI  - The natural resolution of a lumbar spontaneous epidural hematoma and associated
      radiculopathy.
AB  - This is a report of a 37-year-old man who, while lifting a heavy box, developed
      severe low-back pain radiating into the right anterior thigh. The only clinical
      signs were paraspinal muscle spasm and a positive femoral nerve stretch test on
      the right. An electromyographic study demonstrated denervation in the right L2,
      L3, and L4 myotomes and paraspinal muscles. Magnetic resonance imaging (MRI)
      showed a large L1-2 anterior epidural hematoma compressing the spinal cord. The
      patient's pain gradually improved with conservative management and he returned to
      light work after 4 weeks. Repeat electromyographic and MRI studies were normal,
      indicating a resolution of the radiculopathy and hematoma. The diagnosis and
      management of spontaneous epidural hematomas are discussed.

PMID- 8153809
TI  - Suprascapular nerve injury during spine surgery. A case report.
AB  - In long spine surgeries, knee-chest position-associated complications can occur.
      This report describes a case of suprascapular nerve injury that occurred during
      the lengthy surgical procedure. It is postulated that excessive scapula, shoulder
      girdle, and upper arm protraction occurred, resulting in a sling effect
      compression injury of the suprascapular nerve.

PMID- 8153810
TI  - Juvenile compression myelopathy in the cervical spine.
AB  - Juvenile-type distal muscular atrophy of the upper extremities is a condition
      characterized by juvenile onset, muscular atrophy limited to the hand and
      forearm, and lack of definite sensory disturbance. Diagnostic imaging techniques
      and operative findings showed compressive lesions of the cervical spinal cord in
      seven cases showing distal muscular atrophy of the upper extremities. In most of
      these cases, cord compression could be recognized, not during neck extension, but
      during flexion on myelogram, computed tomography, and magnetic resonance imaging.
      All cases underwent anterior spinal fusion to prevent flexion at the affected
      site, and the dural tube was opened to observe the surface of the cervical cord
      in four cases. It was confirmed that cervical myelopathy can occur even in young
      persons with no spondylotic change in the cervical spine.

PMID- 8153811
TI  - Seizure-induced thoracic burst fractures. A case report.
AB  - Musculoskeletal injuries can arise from muscle contraction during generalized
      seizure activity. The most frequently documented injuries are thoracic vertebral
      body compression fractures, proximal femur fractures, and proximal humerus
      fractures occasionally accompanied by dislocation. A case is presented of a
      thoracic burst fracture and bilateral proximal humerus fractures secondary to a
      seizure.

PMID- 8153812
TI  - Solitary infantile myofibromatosis of axis. A case report.
AB  - Lytic lesions of the cervical spine are rare and may be caused by infection or
      tumors. The authors report a rare case of solitary infantile myofibromatosis
      presenting as a lytic lesion of the second cervical vertebral body (C2) and
      odontoid, causing atlanto-axial instability.

PMID- 8153813
TI  - Cerebellar stroke due to vertebral artery occlusion after cervical spine trauma.
      Two case reports.
AB  - The authors report two cases of cerebellar infarction due to vertebral artery
      (VA) occlusion resulting from cervical spine trauma. In one patient with dens and
      C2 body fracture, the left VA was occluded, resulting in a left cerebellar
      infarction. The second patient, with a subluxation of C4 on C5, presented with
      cerebellar swelling and infarction along with acute hydrocephalus secondary to
      bilateral vertebral artery occlusion. Because vertebral artery injuries with
      cervical trauma are rarely symptomatic, they can be easily overlooked. Bilateral
      or dominant vertebral artery occlusion, however, may cause rapid and fatal
      ischemic damage to the cerebellum and brain stem. Rapid recognition and optimal
      treatment for this injury depends on early vertebral artery angiography.

PMID- 8153814
TI  - Cyclic sciatica. A case report.
AB  - We report a case of endometrioma in the pelvic cavity. A 41-year-old woman
      presented with a peculiar periodic sciatica associated with her menses. Computed
      tomography showed an oval-shaped mass in the pelvic cavity compressing the right
      sciatic nerve. To confirm the diagnosis, hormonal therapy through nose dropping
      of buserelin acetate was given to stop menstruation. After treatment, her
      symptoms disappeared completely. When a sciatica is closely related to menses,
      orthopedic surgeons should consider cyclic sciatica resulting from endometrioma
      as a differential diagnosis.

PMID- 8153815
TI  - Cerebrospinal fluid leakage after sacral bar removal. A case report.
AB  - A well recognized tool in the management of sacral fractures is the use of
      extradural sacral bars. This is a case of a previously unreported complication in
      the use of sacral bars: leakage of cerebrospinal fluid after their removal from a
      healed fracture.

PMID- 8153816
TI  - Congenital spondylolisthesis in the upper spinal column. Management of two cases.
AB  - Two cases of congenital spondylolisthesis involving the cervical and thoracic
      spinal column are presented. Both patients presented with significant neurologic
      deficits and responded favorably to stabilization and fusion.

PMID- 8153817
TI  - Adult lumbar scoliosis. Epidemiologic aspects in a low-back pain population.
AB  - The frequency and characteristics of definite lumbar scoliosis in an adult common
      low-back pain population (n = 671) were assessed by a clinical and radiologic
      prospective study. The prevalence was 7.5% (N = 50), increasing with age: 2%
      before 45 years; 15% after 60 years. Scoliosis was revealed by low-back pain in
      adulthood in 86% of the cases. The mean Cobb angle was 21 +/- 11.4 degrees. A
      Cobb angle of more than 30 degrees was noted in 16% of the scoliotics, thus 1% of
      the entire population. The proportion of women increased with the severity of the
      scoliosis. Right and left side scolioses were equally noted. A correlation
      between the Cobb angle and age was found (0.3 degrees/yr; P < 0.05). Rotatory
      olisthesis was noted in 34% of the cases, more often in right side curves (P <
      0.01). The lumbar scoliotic patients were distinguished by a more advanced age
      (62 +/- 12.4 yr vs. 49.6 +/- 15.5 yr; P < 0.001), a greater proportion of women
      (72% vs. 48%; P < 0.01), and a more likely involvement of L3 and L4 radicular
      pain (P < 0.05). Radicular thigh pain was related to unstable curves (P < 0.01).
      The lumbar scoliotic patients thus constitute a subgroup within the low-back pain
      population.

PMID- 8153818
TI  - Sociocultural factors and back pain. A population-based study in Belgian adults.
AB  - A population-based survey of approximately 4000 adults in Belgium, a bi-cultural
      country with a uniform health care system, explored the relationships of socio
      cultural and employment factors to the reported experience of low back pain
      (LBP). Predictors of 1) history of LBP, 2) first LBP, and 3) daily LBP were
      examined by multiple logistic regression analysis. Thirty-three percent of the
      population had current LBP, including 5% experiencing their first episode; 26%
      had past but not current LBP, and 41% had never had LBP. Increasing age (OR >
      2.0, P = .000) and female gender (OR 2.16, P = .000) were associated with history
      of LBP; only gender (OR 1.40, P = .02) was associated with first episode; neither
      was associated with daily LBP. Language was associated with history (OR 1.80, P =
      .000) and first occurrence (OR 1.77, P = .000) but not daily LBP. Among those
      employed, work dissatisfaction was associated with history of LBP (OR > 2.4, P =
      .02) and daily LBP (OR 3.85, P = .02), but not with first episode. The results
      suggest that sociocultural factors influence the expression of LBP, but not the
      risk of chronicity once LBP is reported, and that work satisfaction may not be
      causally related to LBP, but may intervene along with type of occupation in the
      possibility of continuing employment once LBP is present. Prospective studies are
      needed to confirm these results and elucidate causal relationships.

PMID- 8153819
TI  - Incidence of sciatic pain among men in machine operating, dynamic physical work,
      and sedentary work. A three-year follow-up.
AB  - The incidence of sciatic pain among 25-49 year-old men in three different types
      of work: machine operating, dynamic physical work (construction carpenters), and
      office work was assessed prospectively. Postal questionnaires both at the
      beginning and the end of the 3-year follow-up were answered by 1149 men who at
      baseline had no history of sciatic pain. The crude risk ratio of the incidence of
      sciatic pain was 1.6 (95% confidence interval 1.2-2.2) for the machine operators
      and 1.7 (1.3-2.4) for the carpenters when the office workers were referents. The
      adjusted risk ratios were 1.4 (1.0-1.9) and 1.5 (1.1-2.1), respectively. Previous
      history of severe lumbago or other low-back pain increased the risk fourfold.
      Frequent physical exercise and smoking were of borderline significance as
      predictors.

PMID- 8153820
TI  - Low back pain. Epidemiologic aspects and work-related factors in the steel
      industry.
AB  - A cross-sectional epidemiologic study about low back pain (LBP) reports and
      associated factors was conducted in two steel industries. A checklist was used to
      collect information concerning the health, the LBP history, the personal
      characteristics as well as the characteristics of the present and past working
      conditions. This checklist was filled by an interviewer during a free discussion
      with each worker; 618 blue collar workers participated in this study. Lumbar
      symptoms were 66%, 53%, and 25%, respectively, during the lifetime, the 12
      months, and the 7 days before the interview. The multivariate logistic regression
      showed an association with two occupational factors: heavy efforts of the
      shoulders (OR = 1.62) and vehicle driving (OR = 1.15). The other characteristics
      of the working conditions such as physical workload, postures and movements of
      the trunk, or exposure to whole body vibrations were not associated with an
      increased prevalence of LBP.

PMID- 8153821
TI  - Progression of scoliosis in children with myelomeningocele.
AB  - In a retrospective follow-up of 64 patients with myelomeningocele and scoliosis
      of more than 10 degrees, the development of the scoliosis curve was watched. The
      mean follow-up was 4.3 years. Most progression of scoliosis can be expected
      before 15 years of age. Fifty-four percent of the patients with scoliosis of 40
      degrees or more progressed more than 5 degrees per year. Progression was
      dependent on the scoliosis angle. A multivariate model for the prediction of the
      scoliosis progress in a 1-year perspective was applied. The model included the
      current scoliosis angle, the age of the patient, the skeletal level of the
      dysraphism, and the patient's ambulation capacity.

PMID- 8153822
TI  - Brace treatment of scoliosis in children with myelomeningocele.
AB  - In twenty-one children with myelomeningocele and progressive scoliosis, treatment
      of scoliosis was attempted with a Boston type underarm brace. Thirteen children
      finished full brace treatment (average treatment time 2.5 years) and the patients
      were included in a follow-up more than 2 years after the end of treatment with no
      further progression of the scoliosis. Two patients are still undergoing brace
      treatment. Six children were operated due to continued progression of the
      scoliosis. Among 14 patients with scoliosis 45 degrees or less at the start of
      brace treatment, only 1 patient progressed and underwent operation. The brace had
      a temporary effect on severe scoliosis, decreasing the rate of progression.
      Complications were few. The brace caused decubitus ulcer in one patient, and two
      patients developed increased pressure of the urinary tract.

PMID- 8153823
TI  - Prediction of an extruded fragment in lumbar disc patients from clinical
      presentations.
AB  - To determine whether the presence of an extruded lumbar disc prolapse could be
      predicted from clinical symptoms, the authors compared the relative proportions
      of back and leg pain, with operative findings in a prospective observational
      study of 100 lumbar discectomy patients. All cases were assessed by an
      independent observer, blind to the knowledge of the operative findings. Of the 58
      men and 42 women (mean age 42, range 19-75), 47 patients had a subligamentous
      disc protrusion and 53 had an extruded disc fragment. Of 27 patients who
      presented with leg pain only, 26 (96%) were found subsequently to have an
      extruded fragment. Patients with an extruded fragment had a significantly higher
      proportion of leg:back pain (median 99:1) than those with a subligamentous disc
      protrusion (median 75:25, P < 0.001). Patients with leg pain only and those with
      a marked predominance of leg pain over back pain have a high probability of
      harboring an extruded disc fragment.

PMID- 8153824
TI  - Radiographic changes at the coronal plane in early scoliosis.
AB  - The development of structural skeletal changes was evaluated on 132
      anteroposterior radiographs of spines from three scoliotic groups with a Cobb
      angle of up to 30 degrees and a reference control group. Significant wedging of
      the vertebral bodies and disks at the coronal plane was registered in-curves with
      a Cobb angle of 4 degrees or more. Asymmetry of the rib-vertebra angle was found
      in curves with a Cobb angle of 8 degrees or more and was most pronounced in the
      cranial part of the curves. The early simultaneous occurrence of vertebral and
      disk wedging suggests the involvement of an extraspinal factor rather than growth
      disturbance of the vertebral body or of the disk in the early pathomechanism of
      scoliosis.

PMID- 8153825
TI  - Evidence of lumbar multifidus muscle wasting ipsilateral to symptoms in patients
      with acute/subacute low back pain.
AB  - The effect of low back pain on the size of the lumbar multifidus muscle was
      examined using real-time ultrasound imaging. Bilateral scans were performed in 26
      patients with acute unilateral low back pain (LBP) symptoms (aged 17-46 years)
      and 51 normal subjects (aged 19-32 years). In all patients, multifidus cross
      sectional area (CSA) was measured from the 2nd to the 5th lumbar vertebrae (L2-5)
      and in six patients, that of S1 was also measured. In all normal subjects, CSA
      was measured at L4 and in 10 subjects measurements were made from L2-5. Marked
      asymmetry of multifidus CSA was seen in patients with the smaller muscle being on
      the side ipsilateral to symptoms (between-side difference 31 +/- 8%), but this
      was confined to one vertebral level. Above and below this level of wasting, mean
      CSA differences were < 6%. In normal subjects, the mean differences were < 5% at
      all vertebral levels. The site of wasting in patients corresponded to the
      clinically determined level of symptoms in 24 of the 26 patients, but there was
      no correlation between the degree of asymmetry and severity of symptoms. Patients
      had rounder muscles than normal subjects (measured by a shape ratio index),
      perhaps indicating muscle spasm. Linear measurements of multifidus cross-section
      were highly correlated with CSA in normal muscles but less so in wasted muscles,
      so CSA measurements are more accurate than linear dimensions. The fact that
      reduced CSA, i.e., wasting, was unilateral and isolated to one level suggests
      that the mechanism of wasting was not generalized disuse atrophy or spinal reflex
      inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8153826
TI  - A ten-year prospective study of vertebral canal size as a predictor of back pain.
AB  - This prospective study compared ultrasound measurement of the lumbar vertebral
      canal with subsequent back pain; 669 mining and nursing recruits had been
      measured before 1980, and 450 replied to a postal questionnaire in 1990. There
      was no significant difference in the prevalence of back pain or the need to be
      off work with back pain, in those whose canals were above and below the mean.
      However, going to bed with back pain was more frequent in those with small canals
      and approached significance (P = 0.068). Those with small canals were more likely
      to visit doctors and have treatment for back pain. Canal measurement is not a
      predictor for back pain, but as a risk factor for severe back pain in early
      working life, it approaches significance.

PMID- 8153827
TI  - Gadolinium-enhanced magnetic resonance imaging of 36 patients one year after
      lumbar disc resection.
AB  - A prospective study of 36 patients with radicular leg pain and lumbar herniation
      who underwent single-level disc resection is presented. Clinical follow-up was
      combined with a gadolinium-DPTA MRI examination, 1 year after surgery. Disc
      herniation was still present in eight patients and four of these did not have any
      significant radicular pain. Another 15 patients had a small protrusion at the
      site of the former herniation. Twenty-three patients showed evidence of scar
      tissue. The nerve root was displaced in 12 patients and was thickened in 16
      patients, respectively. Clinically, 19 patients recovered from leg pain, 14
      patients improved, and 3 patients remained unchanged compared with preoperative
      symptoms. There was no consistent correlation between postoperative back pain or
      radicular leg pain and MR findings.

PMID- 8153828
TI  - Comparison of contrast-enhanced computed tomography and gadolinium-enhanced
      magnetic resonance imaging one year after lumbar discectomy.
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) with intravenous
      contrast were performed on a prospective group of 35 consecutive patients 1 year
      after surgery for disc herniation. The aim of the study was to compare the two
      methods in the analysis of postoperative changes. Computed tomography showed,
      compared with MRI, more extensive scar tissue in 12 patients and increased
      deformation of the dural sac in 5 patients. However, the nerve root was better
      delineated by MRI, and this facilitated the assessment of root thickening in 13
      patients and root displacement, which could not be seen by CT in seven patients.
      MRI revealed four small protrusions that were not visible with CT. The two
      methods were found to be of equal value in regard to findings such as disc
      herniations and foraminal stenosis, which might influence the surgeons decision
      to perform repeat surgery.

PMID- 8153829
TI  - Computed tomographic follow-up study of 21 cases of nonoperatively treated
      cervical intervertebral soft disc herniation.
AB  - The authors studied the natural evolution of cervical soft disc herniations in 21
      patients with cervical radiculopathy that was successfully treated with
      conservative therapy only. The first computed tomography (CT) examination was
      performed during the acute phase of the radiculopathy, and the second performed
      from 1 to 30 months after healing. The initial CT allowed classification of the
      herniations according to size: nine were considered small, seven medium, and five
      large. Comparison with follow-up scans showed that five of the herniations
      decreased between 0 and 35%, six decreased between 35 and 75% and ten decreased
      between 75 and 100%. The largest herniations were those that had the greatest
      tendency to decrease in size. This tendency could be secondary to the herniation
      breaking through the outer fibers of the anulus and entering the epidural space.

PMID- 8153830
TI  - Digital assessment of MRI for lumbar disc desiccation. A comparison of digital
      versus subjective assessments and digital intensity profiles versus discogram and
      macroanatomic findings.
AB  - During magnetic resonance imaging, a vast amount of digital data on anatomic
      structures is translated into images, which are then assessed subjectively. The
      development of an objective, sensitive method to directly assess the digital data
      would have clear benefits, particularly for clinical research on disc
      degeneration. The study goals were to develop a method of digital assessment of
      disc desiccation and to compare digital signal intensity profiles with
      discographic patterns and macroanatomic findings. Proton density-weighted MRIs
      were obtained from 45 males (9-77 years) and digital analysis was done with a
      freely selectable region of interest facility. The adjacent cerebrospinal fluid
      (CSF) was used as a reference for disc signal-intensity scores, and the disc to
      CSF-intensity ratio provided "adjusted digital scores." The CSF-adjusted digital
      method yielded reproducible scores that correlated with the subjective
      assessments. However, the CSF-adjusted digital scores were more sensitive than
      the subjective assessments, identifying findings that otherwise were undetected
      in younger subjects. Additionally, 10 cadaveric spines were evaluated using MRI
      with T2 and proton density-weighted sequences, discography, and macroanatomic
      dissection. MRI disc-intensity profiles were determined along a midsagittal line
      drawn through the disc. The profile of the digital scores along this line was
      then compared with discograms and macroanatomic sections. In all cases of disc
      degeneration on discograms, changes were present in the intensity profile. Based
      on both the living subjects and the cadaveric specimens, the digital assessments
      and disc intensity profiles appear to demonstrate disc degeneration, particularly
      in early stages.

PMID- 8153831
TI  - Erector spinae lever arm length variations with changes in spinal curvature.
AB  - Magnetic resonance imaging was used to study the effect of different curvatures
      in the lumbar spine on lever arm lengths of the erector spinae musculature.
      Eleven subjects were instructed to simulate static lifts while lying supine in a
      magnetic resonance camera with the lumbar spine either in kyphosis or lordosis. A
      sagittal image of the spine was obtained to analyze the lumbosacral angle and to
      guide the imaging of transverse sections through each disc (L1/L2 to L5/S1).
      Images were analyzed for lever arm lengths of the erector spinae muscle (ES) and
      the erector spinae aponeurosis (ESA), the latter functioning as a tendon for
      superiorly positioned ES muscle portions. The lumbosacral angle (between superior
      surfaces of S1 and L4) averaged 44 degrees in the lordosed, 26 degrees in the
      kyphosed and 41 degrees in a neutral supine position. In lordosis, the lever arm
      lengths were significantly longer than in kyphosis for all levels, averaging 60
      63 mm (ES) and 82-86 mm (ESA). The corresponding values for kyphosis were 49-57
      mm (ES) and 67-77 mm (ESA), respectively. Thus, there was a considerable effect
      (10-24%) of lumbar curvature on lever arm lengths for the back extensor muscles.
      The change in leverage will affect the need for extensor muscle force and thus
      the magnitude of compression in the lumbar spine in loading situations such as
      lifting.

PMID- 8153832
TI  - Effect of strain rate and bone mineral on the structural properties of the human
      anterior longitudinal ligament.
AB  - The effect of strain rate and bone mineral content on the biomechanical
      properties of the human lumbar anterior longitudinal ligament-bone complex was
      studied. Tensile structural properties were determined for 54 such preparations
      subjected to distraction rates ranging from 0.1-230 mm/sec. The ultimate load as
      well as the stiffness of the bone-ligament complex increased more than 50% over
      this strain rate range. A high correlation between bone mineral and structural
      properties of the ligament-bone complex was also noted. These findings suggest
      that, in development and construction of spine models for prediction of injury
      risks, one should consider the effect of different loading rates as well as the
      inherent properties (i.e., bone mineral content) of the biological material.

PMID- 8153833
TI  - Compressive mechanical properties of the human anulus fibrosus and their
      relationship to biochemical composition.
AB  - To enhance understanding of the biomechanical role of the intervertebral disc,
      the compressive properties and biochemical composition of nondegenerate samples
      of anulus fibrosus were determined as a function of radial position, region, and
      level. Because of the large swelling propensity of this tissue, a method was
      developed to test excised specimens while maintaining their in situ geometry and
      hydration. Using an analysis based on linear biphasic theory, the compressive
      modulus, hydraulic permeability, and isometric swelling pressure of the anulus
      fibrosus were determined and correlated with the tissue composition. The findings
      indicate that the anulus fibrosus is inhomogeneous, with regional and radial
      variations in both material properties and biochemical composition. The results
      of this study suggest that both structural and compositional factors may
      determine the mechanical behavior.

PMID- 8153834
TI  - L4-5 isthmic spondylolisthesis. A biomechanical analysis comparing stability in
      L4-5 and L5-S1 isthmic spondylolisthesis.
AB  - The authors have previously reported that the L4-5 isthmic spondylolisthesis
      lesion often progresses more than the L5-S1 lesion in adult patients. This
      biomechanical study compares the in vitro stability of the L4-5 isthmic
      spondylolisthesis lesion compared with the L5-S1 isthmic lesion. The authors also
      analyzed the role of the L5 iliolumbar ligament as a contributing factor to
      stability. Six fresh frozen human cadaveric specimens (L4 to the sacrum including
      the iliolumbar ligamentous complex) were tested by applying 10 Nm flexion
      extension moments. Sagittal plane motion was measured with the specimens intact
      and after sequential transection of the pars interarticulares at L4 and L5 and
      finally with the iliolumbar ligaments cut at L5-S1. L4-5 and L5-S1 both showed
      significant increases in rotation with the pars defect compared with normal (L4-5
      = +2.0, L5-S1 = +3.2 degrees). Decreased translation of L5-S1 occurred with pars
      defect at this level. There were no significant differences at the L5-S1 level
      after sectioning of the iliolumbar ligament. Calculating the percentage
      difference from normal, L4-5 with a pars defect exhibited significantly greater
      relative motion compared with L5-S1 with the same defect; 12% more rotation, 33%
      more shear, and 43% more axial translation. The iliolumbar ligament did not
      appear to contribute to these differences because there was no significant change
      in the L5-S1 kinematics after its transection. These results support the
      hypothesis that L4-5 pars defects are more unstable than L5-S1 lesions. The
      iliolumbar ligament could not be implicated as the major contributing factor in
      these differences.

PMID- 8153835
TI  - Three-dimensional terminology of spinal deformity. A report presented to the
      Scoliosis Research Society by the Scoliosis Research Society Working Group on 3-D
      terminology of spinal deformity.
AB  - Conventional terminology of three-dimensional description of spinal deformity is
      ambiguous and mostly tied to either a frontal or sagittal plane view of the
      spine. The article proposes a rationalized system for describing the shape of the
      spine. The spine is viewed as a line in space ('vertebral body line') with three
      'angulations' specifying the orientation of each vertebra. Four axis systems are
      defined for the whole body, the spine, curve regions, and individual vertebrae,
      respectively. These in turn define the principal planes of the body, spine, curve
      regions, and vertebrae. Curvature can be defined as a local measure at a point on
      the vertebral body line, or as a regional measure between specified end
      vertebrae. Torsion is defined both as a local geometric property of the vertebral
      body line, and as measure of the relative axial plane angulations between
      specified vertebrae. Linear distance measures define the deviations of specified
      vertebrae from the local, regional, spinal, and global axis systems. Practical
      recommendations for positioning patients are made. This new system of terminology
      recognizes the 3-dimensional nature of scoliosis and other spinal deformities and
      is intended to rationalize communication in both research and clinical practice.

PMID- 8153836
TI  - Intervertebral space nerve root entrapment after lumbar disc surgery. Two cases.
AB  - Iatrogenic pseudomeningocele formation after lumbar or cervical spine surgery is
      a well-described complication. Two unusual cases of transdural nerve root
      herniation with subsequent entrapment in the intervertebral space after lumbar
      disc surgery are presented. The reasons for this rare complication and its
      treatment are discussed.

PMID- 8153837
TI  - Epidural lipomatosis. Interest of magnetic resonance imaging in a weight
      reduction treated case.
AB  - An obese patient with bilateral sciatic pain had epidural lipomatosis on magnetic
      resonance examination. Treatment that used a weight-reduction program eliminated
      the symptoms, and after magnetic resonance imaging, revealed reduction of the
      lipomatosis deposits.

PMID- 8153838
TI  - [Magnetic resonance tomography (MRT) in the evaluation of heart disease:
      quantitative determination of aortic regurgitation volume].

PMID- 8153839
TI  - [Dynamic magnetic resonance tomography of the sacroiliac joint: diagnosis of the
      early stages of a sacroiliitis].

PMID- 8153840
TI  - [Magnetic resonance tomography studies of prostatic cancer using a rapid spin
      echo-pulse sequence (Turbo-Spin-Echo--TSE].

PMID- 8153841
TI  - [A 15-year-old female patient from the new provinces with a communicating truncus
      arteriosus].

PMID- 8153842
TI  - [Intraoperative radiotherapy (IORT) in the curative treatment of stomach cancer].

PMID- 8153843
TI  - The recruitment of research participants: a review.
AB  - Social workers are involved in the recruitment of research participants in a
      variety of ways. Increased knowledge regarding recruitment issues will allow
      social workers to expand their role and improve their performance in this area.
      These individuals should be aware that there is a large body of literature
      addressing recruitment. This selective review of the literature prior to mid-1992
      will focus on the Coronary Primary Prevention Trial, volunteer effects,
      recruitment sources, the recruitment process, impediments to recruitment, bias in
      recruitment, the amount of time required to recruit and the impact of recruitment
      and participation on individuals. This will be followed by a discussion of issues
      to be addressed in arriving at solutions to recruitment problems.

PMID- 8153844
TI  - Social work practitioners as researchers: is it possible?
AB  - Social workers are encouraged and often expected to conduct research in addition
      to their clinical duties. Unfortunately, few practitioners seem interested and
      there is usually a lack of tangible supports in most practice settings. To
      counter this, a support group of non-supervisory clinical social workers in a
      Department of Veterans Affairs Medical Center met regularly with a social work
      educator-consultant in order to strengthen research skills, maintain motivation,
      and promote publication. This group successfully published seven articles with an
      additional five in process. In contrast, a second research group at the same
      facility foundered after eight months. Similarities and differences between the
      two groups are discussed. Recommendations are made about how agencies might
      encourage and sustain practitioners in the development and publication of
      clinical research.

PMID- 8153845
TI  - Recognizing cancer as a family disease: worries and support reported by patients
      and spouses.
AB  - Data were obtained via mailed questionnaire from 91 adults with cancer and 78
      spouses of adults with cancer. Findings suggest that spouses and patients worry
      equally about their own personal health, and that spouses worry more about
      patients' futures than the patients do themselves. In addition, spouses and
      patients report participating equally in the treatment process, yet patients
      report receiving significantly more social support than do spouses. The results
      point to the need for expanded attention to the concept of cancer as a "family
      disease," with special emphasis on the unique and often neglected experience of
      spouses of adult cancer patients.

PMID- 8153846
TI  - Social work role in an early ovarian cancer detection program.
AB  - Social Work intervention in an early ovarian cancer detection program has helped
      women who are at high risk for the disease because of family history, make full
      use of the clinic's medical resources. It has provided an enabling component for
      their participation in required medical procedures; has assisted them in dealing
      with unresolved emotions precipitated by their relative's death from cancer
      earlier in their lives; and has helped them move into the next indicated stages
      of medical intervention.

PMID- 8153847
TI  - Operation Desert Storm: the response of a Social Work Outreach Team.
AB  - This paper presents a description of the objectives, planning, observations, and
      reports of a Department of Veteran's Affairs Social Work Outreach Team's efforts
      to work with soldiers returning from Operation Desert Storm. The soldiers
      reported experiences with discrimination, low morale, sexual harassment, and
      fear.

PMID- 8153848
TI  - Professional allocations of counseling service to persons with Alzheimer's
      disease: an exploration.
AB  - Individual, family, and group counseling service recommendations made by
      California's diagnostic and treatment center staff to a clinical sample of
      Alzheimer's disease clients (N = 822) are examined using logistic regression.
      Predictors included the patients' enabling, need, and predisposing
      characteristics. Analysis shows that staff tend to consider fewer patient
      characteristics, and rely more on assessed family problems and payment source
      when deciding whether they recommend counseling to their patients.

PMID- 8153849
TI  - Dietary intake, food preferences, stimulated salivary flow rate, and masticatory
      ability in older adults with complete dentitions.
AB  - This study was conducted to determine whether significant relationships exist
      among the masticatory ability, chewing-stimulated salivary flow rate, food
      preferences, and dietary intake of older adults with complete natural dentitions.
      Pearson r correlations revealed that significant relationships existed between:
      (1) salivary flow rate and eighteen out of the twenty-two nutrients comprising
      dietary intake; (2) masticatory ability and six out of the twenty-two nutrients
      comprising dietary intake; and (3) the perceived frequency of ingestion of the
      thirteen test foods and the dietary intake of thirteen of the nutrients
      comprising dietary intake. No significant relationships were found among salivary
      flow rate, masticatory ability, and food preferences. The amount of saliva
      accumulated in the mouth during the consumption of food may play an important
      role in food choices and subsequent intake of nutrients by older adults.
      Masticatory ability may not play as large a role as salivary flow rate in
      determining the selection and consumption of nutrient-rich foods.

PMID- 8153850
TI  - Congenital diaphragmatic hernia: implications for nitrous oxide use in dentistry.
AB  - The development of diaphragmatic hernias, their associated physical and
      diagnostic signs and symptoms, and the potential complications with nitrous oxide
      use are presented with a case report. Depending upon the location and extent of
      the diaphragmatic defect, portions of the stomach, omentum, liver and/or
      intestine can occupy a portion of the thoracic cavity. Nitrous oxide's solubility
      properties allow for rapid expansion of the herniated bowel, resulting in
      compression of the thoracic organs or strangulation of the herniated abdominal
      viscera. The presence of a diaphragmatic hernia may necessitate a change in
      sedation or anesthesia plans to eliminate the use of nitrous oxide during
      prolonged procedures.

PMID- 8153851
TI  - A prospective survey of hospital ambulatory dental emergencies. Part 2: Follow-up
      to emergency treatment.
AB  - Two hundred and fifty-three patients treated for dental emergencies at the
      University Hospital dental clinic over a three-month period were surveyed by
      telephone 24 to 48 hours and one year after treatment. The purpose was to
      investigate the success of treatment in resolving the chief complaint of pain and
      to determine the compliance with further dental care for the original dental
      problem. The results of the telephone survey showed that: patients available for
      questioning totaled 49.1% at 24 to 48 hours and 28.9% at one year; an 80.7%
      success rate was recorded in resolving pain within 24 to 48 hours; and the
      original emergency problem did not motivate a large number of these patients to
      seek further dental care.

PMID- 8153852
TI  - Pediatric infection with the human immunodeficiency virus (HIV): head, neck, and
      oral manifestations.
AB  - The increasing incidence of HIV infection in the pediatric population is of
      concern for the practicing dentist. Long incubation periods of the virus,
      combined with difficulty in detection, results in many undiagnosed cases of
      prenatal and natal infections with HIV. As a result, many dentists will
      unknowingly treat HIV-positive children. This article presents most common
      features of pediatric HIV infection, placing special emphasis on manifestations
      which affect the head, neck, and oral tissues.

PMID- 8153853
TI  - Israeli dentists: a survey of infection control office practices and care of
      medically compromised patients.
AB  - A survey was conducted by interviewing a randomly selected sample of practicing
      dentists in Israel in 1991. The aim of this study was to evaluate methods of
      infection control in current use and to learn about the access to care for
      medically compromised patients. One hundred seventeen dentists were interviewed.
      This group represented a majority of graduates from Israeli schools (66). With
      respect to infection control, only 28% of the population surveyed routinely uses
      gloves, but 43% use steam autoclave, and 70% use dry-heat sterilization. A very
      high percentage (87%) took a verbal medical history, while a small minority (27%)
      had their patients fill out a written questionnaire. Only occasionally was the
      name of the patient's physician requested or recorded, implying a flaw in
      interprofessional communications. Only 26% of the dentists said they would treat
      patients with hepatitis and/or AIDS. Only about half the dentists accepted
      patients on chemotherapy or radiotherapy or those who were taking anticoagulant
      drugs. Physical access for dental patients in wheelchair or stretcher was
      markedly limited, with referral to regional hospitals the routine for these
      patients.

PMID- 8153854
TI  - Removal of impacted third molars by oral/maxillofacial surgery and general
      dentistry residents.
AB  - The post-operative symptoms of patients who had undergone third molar extractions
      by Oral/Maxillofacial Surgery (OMS) residents were compared with those of
      patients whose extractions were performed by General Dentistry (GD) residents.
      The OMS group had more extractions per visit and were more likely to use
      intravenous sedation than the GD-treated group. No significant differences were
      found when the provider groups were compared by post-operative symptoms such as
      osteitis, infection, trismus, or paresthesia/dysthesia. The pain relief due to
      postoperative analgesics during the immediate 12-hour period was higher for
      patients treated by GD residents. Multiple regression analysis revealed that this
      difference was due to the number of teeth extracted and the complexity of the
      surgical procedure, independent of type of provider.

PMID- 8153856
TI  - Universal access: are we ready?

PMID- 8153855
TI  - Closure of a general practice residency and outpatient program.
AB  - This paper describes the various fiscal and programatic strategies used by a
      carefully managed, institutionally integrated, and financially viable dental
      department that was suddenly told to close its outpatient program and General
      Practice Residency Program. This case history emphasizes the importance of
      external factors and the need for the dental leadership in an institution to be
      certain that the dental department's goals are consistent with the mission of the
      host institution, especially in times of change. As new programs develop and
      existing departments expand, the reasons for the success as well as failure
      experienced by others should be evaluated carefully. This paper adds to this
      understanding.

PMID- 8153857
TI  - A preliminary study into the dental health status of multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is an inflammatory disease of unknown etiology involving
      the central nervous system. Since MS affects the whole body, orofacial aspects of
      the disease must be expected, particularly since loss of muscular coordination
      may result in a diminished ability to maintain oral hygiene. This preliminary
      study examined the dental health status of 22 volunteer MS patients. A
      questionnaire collected data regarding medical and dental histories and socio
      demographic information. Extra- and intra-oral examinations were carried out on
      all subjects to determine the particular dental treatment needs of this special
      group. The DMFT and CPITN scores for this group did not indicate that MS patients
      were more susceptible to dental caries or periodontal disease. However, the
      prevalence of trigeminal neuralgia and symptoms of TMJ dysfunction in the group
      studied indicated that these conditions may be manifest in MS patients and
      warrant further investigations.

PMID- 8153858
TI  - Laparoscopic-assisted colon resection.
AB  - The popularity and success of laparoscopic biliary tract surgery have persuaded
      surgeons to explore other applications for rigid endoscopic surgery. From July
      1990 to February 1993 a total of 65 patients (mean age 57 years; range 41-82)
      underwent attempted laparoscopic colon resection. Indications for surgical
      intervention included cancer (39), adenomatous polyps (14), diverticulosis (10),
      stricture (1), and foreign-body perforation (1). A laparoscopic-assisted
      technique whereby the specimen was removed and the anastomosis was completed
      outside of the abdomen was used in all patients. A dilated umbilical opening was
      used for right-sided lesions and a left-lower-quadrant muscle-splitting incision
      for descending and sigmoid colon resections. Two patients required conversion to
      open laparotomy. There were no deaths and only four complications (pneumonia 1,
      urinary tract infection 1, prolonged ileus 1, and subfascial abscess 1). The mean
      postoperative stay was 4.4 days (range 3-8 days) and the average interval for
      return to normal activity was 8 days. Laparoscopic-assisted colon resection
      appears to be a safe and beneficial option for many patients with pathologic
      disorders of the large intestine. Future clinical trials are needed to fully
      determine the appropriateness of this procedure in patients with localized
      malignancies.

PMID- 8153859
TI  - Diversion colitis. A prospective study.
AB  - A prospective study of patients who had undergone fecal diversion was performed
      in order to determine the incidence of and to characterize better the condition
      known as "diversion colitis." A total of 53 patients were studied. All patients
      underwent endoscopic evaluation of the diverted large bowel. Evidence of colitis
      was found in 48 patients (91%). The colitis was mild in 52%, moderate in 44%, and
      severe in only 4%. Endoscopic findings included: contact irritation or bleeding,
      erythema, and mucosal nodularity. The proximal, "in continuity," colon was
      examined in 86% of patients with colostomies; none were found to have colitis.
      Biopsies were taken of the diverted segment in 94% of patients with colitis and
      from the "in continuity" colon in 78% of patients with colostomies. Similar
      histologic findings were noted on these biopsies and included: mild chronic
      inflammation, lymphoid nodules, and crypt architectural changes. With the
      exception of lymphoid nodules, which were seen more frequently in the inflamed
      diverted colon (P = 0.035), there was no significant difference in the incidence
      of the various histologic changes when the biopsies from the diverted and "in
      continuity" large bowel were compared. Rectal washings and stool samples were
      sent for bacterial cultures, ova, and parasite analysis, and C. Diff. toxin
      titers in the majority of patients; all but 1 were negative. Symptoms relating to
      the diverted bowel were elicited in only 3 patients (6%). Stomal closure was
      carried in 70% of patients. Postclosure endoscopy in 21 patients revealed full
      resolution of the colitis in all. Diversion colitis occurs in almost all diverted
      patients. It uniformly resolves following stomal closure.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8153860
TI  - Hemodynamic and respiratory effects of pneumoperitoneum and PEEP during
      laparoscopic pelvic lymphadenectomy in dogs.
AB  - Extended laparoscopic operations are being performed increasingly in high-risk
      patients. To assess the effects of increased intraabdominal pressure (IAP) and
      positive end-expiratory pressure (PEEP) on the hemodynamic and respiratory system
      during extended procedures a carbon dioxide pneumoperitoneum was artificially
      induced in 10 dogs undergoing laparoscopic pelvic lymphadenectomy. An increase in
      IAP up to 15 mmHg had no negative effect on the cardiovascular system. However,
      the combination of an increased IAP (10-15 mmHg) with PEEP (8 cmH2O) markedly
      depressed the hemodynamic variables. Measurement of arterial carbon dioxide and
      fractional end-tidal carbon dioxide revealed significant CO2 retention. We
      conclude from the results that laparoscopic pelvic lymphadenectomy should be
      performed in high-risk patients only under general anesthesia with expanded
      cardiopulmonary monitoring.

PMID- 8153861
TI  - Training in laparoscopic cholecystectomy. Quantifying the learning curve.
AB  - There is no clear consensus on the best way to train general surgeons to perform
      laparoscopic cholecystectomy (LC). We attempted to quantify the "learning curve"
      for 86 surgeons attending eight consecutive 3-day, three-pig courses in LC. Each
      step of the operation was scored by the instructor for successful performance:
      Uncomplicated pneumoperitoneum (p), cystic duct and artery dissection (cd),
      artery and duct clipping (cc), operative cholangiography (oc), gallbladder
      dissection without holes (gd), liver bed hemostasis (h), gallbladder removal in
      one piece (i), and no abdominal organ injury (in). As well, operative time,
      method of dissection, and contact Nd: YAG or electrocautery were recorded. The
      percentage of students successfully completing each task for the first and third
      pigs on which they acted as surgeon was as follows: [table: see text] The
      operative time for the first and third pigs was 1.3 +/- 0.56 and 0.70 +/- 0.34
      (mean +/- SD) h, respectively (P < 0.01). When students were trained with the
      contact Nd: YAG laser there was more blood loss than with electrosurgery (P <
      0.001). Statistically significant improvement could only be demonstrated in the
      most difficult task, gallbladder dissection without perforation, but that task
      had not been mastered by the end of 3 days. The flat portion of the laparoscopic
      cholecystectomy "training curve" had not been reached by the end of the program.

PMID- 8153862
TI  - Reusable instruments are more cost-effective than disposable instruments for
      laparoscopic cholecystectomy.
AB  - Health care costs are rising rapidly, and surgeons can play a role in limiting
      costs of operations. Of the 600,000 cholecystectomies performed each year in the
      United States, approximately 80% are performed with laparoscopic technique. The
      purpose of this study was to compare the costs of reusable vs disposable
      instruments used during laparoscopic cholecystectomy. The costs to the hospital
      of reusable and disposable instruments were obtained. Instruments studied were
      the Veress needle, trocars and sleeves (two 10 mm and two 5 mm), reducers, clip
      appliers, and clips. In addition, the costs of sterilization and sharpening for
      reusable instruments were calculated. The cost of reusable instruments was based
      on an assumed instrument life of 100 cases. Data from three private hospitals and
      a Canadian university hospital were collected and examined. Data from the four
      hospitals revealed that the costs of reusable instruments per case were $46.92
      $50.67. The comparable costs for disposable instruments were $330.00-$460.00 per
      case. Theoretical advantages of disposable instruments such as safety, sterility,
      and better efficiency are not borne out in literature review. In addition, the
      environmental impact of increased refuse from disposable instruments could not be
      exactly defined. With the consideration of significant cost savings and the
      absence of data demonstrating disadvantages of their use, reusable instruments
      for laparoscopic cholecystectomy, are strongly recommended.

PMID- 8153863
TI  - A nation's experience in laparoscopic cholecystectomy. Prospective multicenter
      analysis of 3722 cases.
AB  - In a national prospective multicenter study 3,722 laparoscopic cholecystectomies
      (LC) performed by 179 surgeons in 50 institutions were analyzed with special
      regard to technique and complications. Conversion to open cholecystectomy was
      necessary in 259 patients (7.0%), either without intraoperative complications
      (4.5%) or due to intraoperative complications (2.5%). Three patients (0.08%) died
      within 30 days after operation and a total of 39 patients (1.0%) had to be
      reoperated; 22 (0.6%) bile duct injuries were registered. Common bile duct (CBD)
      stones were treated mainly by ERCP. In eight cases laparoscopic removal of common
      bile duct stones was attempted, and it was performed successfully in six
      patients. Postoperatively patients were discharged home after a mean of 4.4 days
      and returned to work after 14.0 days (range: 2-28). Laparoscopic cholecystectomy
      became the golden standard to remove the gallbladder, but further development is
      needed to establish laparoscopic treatment of biliary tract stones in the near
      future.

PMID- 8153864
TI  - Role of laparoscopic cholecystectomy in treating gallbladder polyps.
AB  - Since the application of laparoscopic cholecystectomy (Lap C) to gallbladder
      polyps has not yet been fully evaluated, we performed Lap C on 26 patients with
      gallbladder polyps. Pathological examinations showed adenocarcinoma in three
      patients, adenoma in two, and cholesterol polyp in 21. Preoperative diagnoses of
      the cases with adenocarcinoma were a cholesterol polyp in one patient and an
      adenoma in two. Adenocarcinoma was confirmed to reside in the mucosa without any
      invasion of lymphatic ducts or small vessels in the three patients. This
      procedure was considered to be sufficient for this grade of cancer, and,
      therefore, no additional operations were performed. At present, our policy is to
      resect by Lap C a gallbladder polyp having a maximum size larger than 10 mm and a
      tendency to grow or presenting with suspicion of adenoma. When cancer is
      suspected by preoperative examinations, however, traditional surgery may be
      recommended.

PMID- 8153865
TI  - Laparoscopic gastrostomy versus percutaneous endoscopic gastrostomy. A
      comparison.
AB  - A retrospective study was carried out at our institution to compare patients who
      underwent percutaneous endoscopic gastrostomy (PEG) to those who underwent
      laparoscopic gastrostomy (LG). There were 17 patients who had a PEG with a mean
      age of 81 years (43-97 years). The procedure time, including complete esophago
      gastroduodenoscopy, averaged 28 min. There were four deaths (23%) in a 30-day
      period, but none of these were directly related to the procedure. The LG group
      consisted of 14 patients with a mean age of 66 years (20-94 years). Mean duration
      of the procedure was 18 minutes. Thirty-day mortality rate was 35% (five
      patients) with one death (7%) directly related to the tube. Indications for
      gastrostomy were similar in both groups, being predominantly inability to eat
      and/or recurrent aspiration. However, LG was done because of 4 technical
      failures, 5 patients with tumors of the head and neck, 2 patients with esophageal
      obstruction and radiation stenosis precluding safe PEG, and 1 patient with hiatal
      hernia; 2 LGs were performed at the surgeon's preference. Outcomes for LG and PEG
      were comparable. LG is a suitable, safe alternative to PEG in selected patients
      who cannot undergo gastroscopy and should be considered the procedure of choice
      in patients with head and neck tumors or intrathoracic pathology that prevents
      PEG.

PMID- 8153866
TI  - Laparoscopic distal pancreatectomy in the porcine model.
AB  - Our aim was to assess the feasibility and safety of laparoscopic distal
      pancreatectomy in an animate model. After developing the technique in acute
      animal experiments, laparoscopic distal pancreatectomy was performed in five
      young domestic pigs. Five trocars were used (2-10 mm, 2-12 mm, 1-11 mm) for video
      laparoscopic access to the peritoneal cavity. The operations were performed
      without complication in 62-95 min (mean +/- SEM, 77 +/- 7 min). Each animal
      tolerated oral feedings on the first postoperative day and subsequently gained 6
      11 kg (10 +/- 2 kg) in the 4-7-week interval prior to sacrifice. Although there
      was a significant increase in serum amylase on the first postoperative day, this
      was associated with a comparable increase in hematocrit, possibly representing
      hemoconcentration. The weight of the laparoscopically resected pancreatic segment
      ranged from 16 to 36 g (19 +/- 2 g) while that of the pancreatic head at
      sacrifice was 13-29 g (21 +/- 3 g). At the time of sacrifice, there were few
      intraabdominal adhesions and no evidence of fluid collection or pancreatitis. The
      staple line across the body of the pancreas was grossly intact in all animals. We
      conclude that laparoscopic distal pancreatectomy in the porcine model is feasible
      and safe. It may therefore be possible to perform laparoscopic distal
      pancreatectomy in humans.

PMID- 8153867
TI  - Robotically assisted laparoscopic surgery. From concept to development.
AB  - The evolution of laparoscopy from a monocular view to the video screen has
      enabled all in the operating room to see the procedure. This has meant the
      surgeon must rely on an assistant to hold the scope, which has many drawbacks.
      Robotic enhancement technology creates a symbiotic relationship between the
      surgeon and robot and leads to great improvement in the performance of the case.

PMID- 8153868
TI  - Thoracoscopic esophagectomy in Pakistan.

PMID- 8153869
TI  - The biology of complement. Introduction.

PMID- 8153870
TI  - Mammalian lectins in activation and clearance mechanisms involving the complement
      system.
AB  - CRP and the mammalian lectins containing collagen-like structure (collectins) can
      clearly participate in a variety of antibody-independent recognition and
      clearance mechanisms which result in the neutralisation and elimination of
      pathogenic organisms (Fig. 2). Only CRP and MBP appear to have the capacity to
      activate complement, and while all the collectins (MBP, SP-A, SP-D and
      conglutinin) can utilise the C1q receptor, only conglutinin shows specificity for
      iC3b. The C-type lectin domains in the globular heads of the collectins have the
      capacity to recognise a range of specific carbohydrate structures which are found
      on the surfaces of pathogens commonly associated with infections in blood, lung
      and amniotic fluids. The proposed presentation of the carbohydrate-collectin
      complex to C1q receptors, via the collagen-like regions in the collectins is an
      attractive hypothesis for the triggering of protective mechanisms and there are
      already a number of publications which support this view. However, the precise
      manner by which these collagen 'stalks' interact with the C1q receptor and the
      complete characterisation of the receptor on a variety of different cell types
      remains to be elucidated. Similarly, whether or not there is a role for any of
      these lectins in autoimmunity/immunopathology has not, as yet, been addressed.

PMID- 8153871
TI  - Complement resistance in microbes.

PMID- 8153872
TI  - Complement-related proteins in pathogenic organisms.

PMID- 8153873
TI  - Membrane proteins that protect against complement lysis.

PMID- 8153874
TI  - Complement deficiency and immune complex disease.

PMID- 8153877
TI  - Stereochemical requirements for pseudoirreversible inhibition of opioid mu
      receptor binding by the 3-methylfentanyl congeners, RTI-46144 and its
      enantiomers: evidence for different binding domains.
AB  - Fentanyl and its congeners are of interest not only because of their clinical
      applications, but also because certain members of this series of opioid
      analgesics exhibit unique properties, such as acting as pseudoirreversible
      inhibitors of mu receptor binding, both in vitro and in vivo. Previous studies
      showed that pretreatment of membranes with (+)-cis-3-methylfentanyl resulted in a
      lower affinity interaction of [3H]ohmefentanyl with the mu binding site, as well
      as an increased dissociation rate. The present study was undertaken to determine
      the stereochemical requirements for pseudoirreversible inhibition of mu receptor
      binding using the methylfentanyl congeners, (+-)-cis-N-[1-(2-hydroxy-2
      phenylethyl)-3-methyl-4-piperidyl]-N- phenylpropanamide HCl (RTI-4614-4) and its
      four resolved enantiomers. AR configuration of the 2-hydroxy group was essential
      for high affinity binding and pseudoirreversible inhibition. The two enantiomers
      with this configuration, 1b((2R,3R,4S)-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4
      piperidyl]-N- phenylpropanamide oxolate) and 1c 1c ((2R,3S,4R)-N-[1-(2-hydroxy-2
      phenylethyl)-3-methyl-4-piperidyl]-N- phenylpropanamide HCl), acted as
      pseudoirreversible inhibitors of the mu receptor as labeled with [3H][D-Ala2
      MePhe4,Gly-ol5]enkaphalin, [3H]fentanyl or [3H]etorphine. RTI-4614-4, 1b, and 1c
      decreased the Bmax of [3H][D-Ala2-MaePhe4,Gly-ol5]enkepalin binding sites without
      altering the dissociation rate. These drugs had a lesser effect on steady-state
      [3H]fentanyl and [3H]etorphine binding but did produce statistically significant
      changes in the parameters of the two-component dissociation model, which
      accurately described the dissociation of these [3H]ligands. Viewed collectively,
      these data indicate that the mechanism of the pseudoirreversible inhibition
      appears to depend on the radioligand used to label the mu receptor. To explain
      these data, a pseudoallosteric model is proposed that postulates that certain mu
      ligands bind to different domains of the drug recognition site of the mu receptor
      and that the prebinding of pseudoirreversible inhibitors to the recognition site
      changes the domains available to a radioligand, leading to alterations in steady
      state binding levels and dissociation kinetics.

PMID- 8153875
TI  - Therapeutic uses of recombinant complement protein inhibitors.

PMID- 8153876
TI  - Dopamine-immunoreactive axon varicosities form nonrandom contacts with GABA
      immunoreactive neurons of rat medial prefrontal cortex.
AB  - Recent postmortem studies have suggested that reduced gamma-aminobutyric acid
      (GABA)ergic activity in limbic cortex may be one component to the pathophysiology
      of schizophrenia. This hypothesis has underscored the importance of knowing
      whether midbrain dopamine afferents interact extensively enough with inhibitory
      interneurons to suggest a direct functional relationship. Toward this end, a
      double immunofluorescence approach combined with confocal laser scanning
      microscopy has been used to localize dopamine and GABA simultaneously in rat
      medial prefrontal cortex. The results confirm studies from other laboratories
      showing a rich network of dopamine-immunoreactive fibers forming a gradient
      across the cortical laminae, with deeper layers having the highest density. When
      viewed with oil immersion optics, dopamine-immunoreactive fibers were frequently
      found to be in close apposition with GABA-immunoreactive cell bodies. The
      percentage of GABA-containing neurons showing such contacts was highest in layer
      VI (65%) and progressively decreased toward layer I (9%). Varicose regions of the
      dopamine fibers were typically present at the point of contact with a GABA
      immunoreactive cell body. Using an immunoperoxidase technique to localize
      dopamine fibers and cresyl violet staining to visualize neurons simultaneously,
      two separate statistical analyses were performed to assess whether the frequency
      of contacts between dopamine fibers and cell bodies in general may be due to
      random effects. In layer VI, a high percentage of both pyramidal and nonpyramidal
      neurons were found to be in contact with dopamine varicosities (71% and 76%,
      respectively), but these were not significantly different from that observed for
      GABA-containing cells (65%) in double-immunofluorescence specimens. A Chi-square
      statistical test was used to compare the observed and predicted number of
      varicosities forming cell body contacts. This analysis indicated that the
      percentage of dopamine varicosities (30%) that form appositions with cell bodies
      is much greater than would be expected if these appositions were due to random
      effects (15%). Moreover, using an estimate of intensity for a stationary Poisson
      process, it was again found that random effects can not account for these
      interactions (P = 0.01). Taken together with earlier electron microscopic studies
      from other laboratories, the present findings support the idea that GABAergic
      interneurons have extensive interactions with dopamine varicosities. While these
      interactions are not unique to GABAergic cell bodies, they suggest that
      inhibitory interneurons can play a direct role in mediating the effects of
      midbrain dopamine afferents in rat medial prefrontal cortex.

PMID- 8153878
TI  - Development of dopamine-beta-hydroxylase-positive fiber innervation of the rat
      hippocampus.
AB  - Development of the noradrenergic fiber innervation of the rat hippocampus by the
      locus coeruleus was examined immunohistochemically in fixed tissue from animals
      aged 4 days through 55 days postnatal. The presence of tyrosine hydroxylase (TH)
      and dopamine-beta-hydroxylase (DBH) immunoreactive cells and fibers was evaluated
      in sections of hippocampus and locus coeruleus. Large, multipolar TH- and DBH
      positive cells with long beaded fibers were visible within locus coeruleus at all
      ages; no immunopositive cell bodies were found in hippocampus. In hippocampal
      sections from mature animals (PN55), the highest density of DBH-stained fibers
      was found in stratum lucidum of CA3 and in the hilus and inner molecular layer of
      the dentate gyrus. Whereas similar patterns of fiber positivity were found at
      PN21 and PN10 (although with somewhat reduced density of immunopositive fibers),
      the pattern was quite different at PN4. Although fiber staining was relatively
      sparse at PN4, relative density of DBH fibers was highest in stratum radiatum of
      CA1 and subiculum. This change in staining pattern suggests that noradrenergic
      function in hippocampus may change as the rat matures. Double immunofluorescence
      techniques showed an overlap of DBH and TH positive fibers in all hippocampal
      regions at all ages. DBH immunostaining appeared to be somewhat more sensitive
      than the TH staining. These data made it impossible to confirm the presence of
      significant numbers of nonnoradrenergic, catecholamine-containing fibers in
      hippocampus.

PMID- 8153879
TI  - A drug that facilitates glutamatergic transmission reduces exploratory activity
      and improves performance in a learning-dependent task.
AB  - A recently developed benzamide compound which facilitates glutamate receptor
      mediated synaptic responses was used to test behavioral consequences of enhanced
      glutamatergic transmission. The drug was found to depress exploratory activity by
      rats in a novel environment. At a dose below threshold for causing such effects,
      drug-treated and control rats exhibited no evident behavioral differences during
      the acquisition phase of a radial maze experiment. Yet, when tested 2.5 h later,
      experimental animals were more likely than controls to choose maze arms that had
      not been entered during the acquisition session, suggesting that the drug
      enhanced retention of information about prior choices and the maze environment.

PMID- 8153880
TI  - [Patient hotel--break with tradition].

PMID- 8153882
TI  - [Home nursing--a rainy evening].

PMID- 8153881
TI  - [Patient hotel--for the healthy sick].

PMID- 8153883
TI  - [Home nursing--chaos and croissants].

PMID- 8153884
TI  - [Kashmir--incredible brutality].

PMID- 8153885
TI  - [Protection for confidential information].

PMID- 8153886
TI  - [Clinical nursing--rehabilitation].

PMID- 8153887
TI  - [A miserable reception].

PMID- 8153888
TI  - [Unemployment insurance--we don't get enough money for sick days].

PMID- 8153889
TI  - [The unvarnished truth].

PMID- 8153890
TI  - [Senile dementia--an evening in the protected ward].

PMID- 8153891
TI  - [Management--a desk in the hallway].

PMID- 8153892
TI  - [Senile dementia--chemical control. Interview by Lars Peter Bergqvist].

PMID- 8153893
TI  - [Clinical nursing--rapid return home after hip fracture].

PMID- 8153894
TI  - Hold-harmless clauses: a "Q & A".

PMID- 8153895
TI  - Controversies in the diagnosis and treatment of temporomandibular disorders: an
      updated review of the literature.
AB  - The purpose of this literature review is to examine some of the controversies
      related to the diagnosis and treatment of temporomandibular disorders. The main
      issues are the role of occlusion as an etiologic factor of temporomandibular (TM)
      disorders and the diagnostic significance of various radiological findings with
      respect to TM disorders. Only further research by scientific methodology into
      these complex areas will aid in resolving these issues.

PMID- 8153896
TI  - What is an electronic patient record?

PMID- 8153897
TI  - The future of dentistry? Persons over 65!

PMID- 8153898
TI  - Behavioral influences of intraoral video and long-term wellness planning.

PMID- 8153899
TI  - The electronic environment: understanding the process.

PMID- 8153900
TI  - Your X-ray inspection could be a disaster.

PMID- 8153901
TI  - Lasers in general dentistry and periodontics.

PMID- 8153902
TI  - [Classification of sleep disorders].
AB  - Abnormal sleep can be insufficient, which constitutes insomnia; it can be
      excessive or inappropriate, which is hypersomnia, it can be misplaced with
      respect to the normal sleep-wakefulness rhythm, or it can be accompanied by
      various phenomena which do not belong to sleep itself (i.e. parasomnia). This is
      the format of most traditional classifications of sleep disorders. A modern
      classification has been introduced in 1990 and contains the description of 88
      different sleep disturbances. They are classified in the main categories of
      dyssomnia, parasomnia and sleep disorders associated with psychiatric,
      neurological or somatic conditions. This classification is an excellent tool for
      the practice of sleep medicine and for the study of sleep disorders.

PMID- 8153903
TI  - [Epidemiology of sleep disorders].
AB  - Epidemiological investigations on subjectively reported sleep disturbance suggest
      an average prevalence of 26.2%. About 12.8% of the general population suffer from
      moderate to severe sleep disturbance. With a narrow definition, a prevalence of
      disorders of initiating and maintaining sleep associated with daytime sleepiness
      of 1.6% was found. Female gender and increasing age are risk factors for sleep
      disturbances. Psychological stress and psychiatric symptoms, especially anxiety
      and depressive disorders, are associated with sleep disturbances.

PMID- 8153904
TI  - [Actometry for the objective assessment of sleep disorders].
AB  - The actometer is worn on the wrist and stores the sum of the signals induced by
      movements in a solid-state memory. If the data are collected at one-minute
      intervals for example, they are fed into a personal computer and printed
      graphically after at least 21 days. The method serves for long-term recording of
      the rest-activity rhythm and its disturbances, and the movements occurring during
      sleep under normal life conditions. Furthermore, sleep disturbances as well as
      the effect of drugs on sleep and the results of therapeutic interventions can be
      objectively determined. Research and clinical applications are described.

PMID- 8153905
TI  - [Sleep disorders and depression].
AB  - The concept whether sleep alterations are neurobiologically fundamental in the
      pathogenesis of depression is a main issue of two research directions. Firstly,
      clinical studies investigate if EEG-correlates provide a useful and valid
      indicator of depression, secondly development of sleep regulation models in
      experimental sleep research made it possible to further explore the relationship
      between sleep and affective illness.

PMID- 8153906
TI  - [Parasomnias].
AB  - Parasomnias are frequent. They usually represent either the exaggeration of a
      physiological phenomenon (e.g. sleep starts) or a non-disturbing, idiopathic and
      usually benign sleep disorder (e.g. sleep talking and bruxism), which need only
      counseling and improvement of sleep hygiene. However, occasionally parasomnias
      are of clinical relevance. They can cause insomnia or hypersomnia (e.g.
      'myoclonus nocturnus'), psychosocial stress (e.g. sleep-related enuresis and
      sleep walking) and injuries to oneself and others (e.g. REM-parasomnia). Finally,
      they can be symptomatic of neurological and medical disorders (e.g. sleep
      paralysis and 'myoclonus nocturnus'). In these cases special investigations
      including video-polysomnography can establish a correct diagnosis and allow a
      specific treatment.

PMID- 8153907
TI  - [Sleep apnea].
AB  - Regular and unobstructed breathing during the night is the prerequisite for an
      undisturbed and restful sleep. The most prevalent nocturnal breathing disturbance
      with morbid consequences is the obstructive sleep apnea syndrome. Forms severe
      enough to need therapy and, therefore, a thorough work-up, can be usually
      detected by a detailed history. Pathophysiology, clinical findings, differential
      diagnosis as well as work-up and therapy of the sleep apnea syndrome are
      discussed.

PMID- 8153908
TI  - [Chronobiological sleep disorders and their treatment possibilities].
AB  - A temporal discrepancy between the endogenous sleep-wake cycle and the daily
      structure of the surrounding social network are characteristic for
      chronobiological sleep disturbances. Activity rhythms that are in abnormal
      relation to the environment are more frequent than commonly assumed. They can
      arise either from external causes (such as shift-work or jet-lag) or as a result
      of internal changes promoting abnormal sleep behaviour. Structuring daily
      activities by paying attention to natural daylight (dawn and dusk) and to the
      social routine strengthen the synchronizing effect of external timekeepers
      necessary for the concordance between inner and outer rhythmic phenomena.
      Treatment of chronobiological sleep/wake-cycle disturbances require correct
      diagnosis and modification of their causes, particularly changes in habits
      consolidating such disturbances. Early recognition of a chronobiological sleep
      disorder can reduce the risk of misuse of sleeping pills, caffeine and nicotine.
      Recently developed treatment approaches such as bright light, the pineal hormone
      melatonin and vitamin B12 have provided promising results.

PMID- 8153909
TI  - [Pharmacotherapy of sleep disorders].
AB  - Benzodiazepines and related drugs are the hypnotics of first choice. They shorten
      sleep latency, enhance sleep continuity and may prolong sleep duration. Their
      undesired effects include a persistent day-time sedation and ataxia when getting
      up at night. There is some risk of habit formation and dependence. For treating
      an acute insomnia, the prescription of hypnotics should be limited to a short
      duration (smallest package size), for treating chronic forms of insomnia they
      should have only an adjuvant role in therapy.

PMID- 8153910
TI  - [Non-drug therapy of sleep disorders].
AB  - This contribution focuses on psychological aspects which can underlie disturbed
      sleep or may occur reactively to somatically determined insomnia. Therefore,
      treatment of insomnia should start out with several explanatory interviews with
      the patient, in which all subjective evaluations of sleep and associated events
      are investigated carefully. During several weeks the patient assesses his sleep
      quality, sleep-related behaviours and mood by means of questionnaires. This
      information is to be considered in the further diagnostic process and helps to
      choose adequate therapeutic interventions. Therapeutic help includes a broad
      variety of possible steps: general information about sleep, sleep hygiene rules,
      relaxation advice, cognitive techniques or psychotherapy.

PMID- 8153911
TI  - Primary tracheal tumours.

PMID- 8153912
TI  - Respiratory muscle strength after upper abdominal surgery.

PMID- 8153913
TI  - To help patients control asthma the clinician must be a good listener and
      teacher.

PMID- 8153914
TI  - Primary tracheal tumours: a national survey.
AB  - BACKGROUND: Primary tracheal tumours are rare, so few physicians have extensive
      experience of their management. No direct comparisons have been made of surgical
      and radiotherapy treatment. METHODS: A postal survey of cases presenting in the
      last 10 years in the United Kingdom was conducted. Results were expressed as
      cumulative survival and survival curves were compared by the log rank test.
      RESULTS: Three hundred and twenty one patients were recruited. Overall five year
      survival rates were 25% for squamous cell carcinomas, and 80% for adenoid cystic
      carcinoma; 62% received radiotherapy but only 10% underwent surgery. Small cell
      carcinoma was more common than expected with an incidence of 6%. In patients with
      squamous carcinoma improved survival was seen in those with tumour in the upper
      trachea. High dose radiotherapy was more effective than low dose only in tumours
      of the upper trachea and in squamous carcinoma. In adenoid cystic carcinoma no
      significant difference in survival rate was seen between treatment with
      radiotherapy and surgery. No histological diagnosis was made in 44 patients, the
      most common reason being fear over the safety of fibreoptic bronchoscopy;
      however, this group had a cumulative survival at five years of 46%. CONCLUSIONS:
      Survival may be somewhat better in cases with tracheal tumours than in those with
      bronchial tumours. Small cell carcinoma is less rare than was previously thought.
      Upper tracheal tumours may merit more aggressive therapy. It is important to make
      a histological diagnosis even if rigid bronchoscopy is necessary, and referral to
      specialist centres is recommended. A larger prospective study is required to
      compare the value of surgery and radiotherapy.

PMID- 8153915
TI  - Effect of aminophylline on respiratory muscle strength after upper abdominal
      surgery: a double blind study.
AB  - BACKGROUND: The effect of aminophylline on maximum respiratory muscle strength in
      patients undergoing upper abdominal surgery was investigated. METHODS: An open
      pilot study was performed in which aminophylline was administered continuously
      for 48 hours after surgery (protocol I). In a second group of subjects
      aminophylline was given for 24 hours after cholecystectomy in a double blind
      placebo controlled trial (protocol II). Twelve patients participated in the pilot
      study (group A) and 25 in protocol II of which 14 received aminophylline (group
      B) and 11 placebo (control, group C). Respiratory muscle strength was assessed by
      measuring mouth pressures during maximum static inspiratory and expiratory
      efforts. Forced expiratory volume in one second (FEV1), forced vital capacity
      (FVC), vital capacity (VC), inspiratory maximum pressures (PImax), expiratory
      maximum pressures (PEmax) were measured 24 hours preoperatively, PImax and serum
      theophylline 24 hours postoperatively, and FEV1, FVC, VC, PImax, PEmax, and serum
      theophylline 48 hours after surgery. RESULTS: FEV1, FVC, and VC decreased in all
      groups of patients at +48 hours. PImax fell at +24 hours and +48 hours but this
      decrease was significantly smaller in the two groups who received aminophylline
      than in the control group. PEmax showed a decrease at +48 hours but this
      reduction was similar in all three groups studied, independent of the treatment
      given. These data suggest that either aminophylline had a protective effect only
      on the inspiratory muscles or, most probably, that the effect of aminophylline
      was central, reducing the phrenic nerve inhibition induced by cholecystectomy and
      thus improving diaphragmatic function. CONCLUSIONS: Upper abdominal surgery
      decreases inspiratory and expiratory muscle strength and aminophylline has a
      protective effect only on inspiratory muscle function. This may have important
      clinical applications in minimising pulmonary complications after
      cholecystectomy.

PMID- 8153916
TI  - Lung volume restriction in patients with chronic respiratory muscle weakness: the
      role of microatelectasis.
AB  - BACKGROUND: It is well established that patients with longstanding weakness of
      the respiratory muscles have a reduction in lung distensibility. Although this
      occurs in most patients without any radiographic changes suggesting parenchymal
      lung disease, it has been attributed to the development of microatelectasis.
      METHODS: A high resolution computed tomographic (CT) scanner was used in eight
      patients with traumatic tetraplegia and six patients with generalised
      neuromuscular disorders to look for areas of atelectasis. With the patient in the
      supine posture scans of 1 mm thickness were obtained at total lung capacity at
      intervals of 1 cm from the apex to the base of the lung. RESULTS: Vital capacity,
      total lung capacity, and inspiratory muscle strength were reduced to a mean of
      59.5%, 73.9%, and 51.1% of predicted values, respectively. Static expiratory lung
      compliance was decreased in 12 of the 14 patients and averaged 69.1% of the
      predicted value. The CT scans revealed only small areas of atelectasis in one
      tetraplegic patient and in one patient with a generalised neuromuscular disorder;
      no parenchymal abnormality was seen in the other 12 patients. CONCLUSIONS: In
      many patients with chronic weakness of the respiratory muscles the reduced lung
      distensibility does not appear to be caused by microatelectasis. It might be
      related to alterations in elasticity of the lung tissue.

PMID- 8153917
TI  - Recruitment of some respiratory muscles during three maximal inspiratory
      manoeuvres.
AB  - BACKGROUND: A study was undertaken to determine the level of recruitment of the
      muscles used in the generation of respiratory muscle force, and to ascertain
      whether maximal diaphragmatic force and maximal inspiratory muscle force need to
      be measured by separate tests. The level of activity of three inspiratory muscles
      and one expiratory muscle during three maximal respiratory manoeuvres was
      studied: (1) maximal inspiration against a closed airway (Muller manoeuvre or
      maximal inspiratory pressure (MIP)); (2) maximal inspired manoeuvre followed by a
      maximal expiratory effort (combined manoeuvre); and (3) maximal inspiratory sniff
      through the nose (sniff manoeuvre). METHODS: All the manoeuvres were performed
      from functional residual capacity. The gastric (PGA) and oesophageal (POES)
      pressures and their difference, transdiaphragmatic pressure (PDI), and the
      integrated EMG activity of the diaphragm (EDI), the sternomastoid (ESTR), the
      intercostal parasternals (ERIC), and the rectus abdominis muscles (ERA) were
      recorded. RESULTS: Mean (SD) PDI values for the Muller, combined, and sniff
      manoeuvres were: 127.6 (19.4), 162.7 (22.2), and 136.6 (24.8) cm H2O,
      respectively. The pattern of rib cage muscle recruitment (POES/PDI) was similar
      for the Muller and sniff manoeuvres (88% and 80% respectively), and was 58% in
      the combined manoeuvre, confirming data previously reported in the literature.
      Peak EDI amplitude was greater during the sniff manoeuvre in all subjects (100%)
      than during the combined (88.1%) and Muller (61.1%) manoeuvres. ESTR and EIC were
      more active in the Muller and the sniff manoeuvres. The contribution of the
      expiratory muscle (ERA) to the three manoeuvres was 100% in the combined, 26.1%
      for the sniff, and 11.5% for the Muller manoeuvre. CONCLUSIONS: Each of these
      three manoeuvres results in different mechanisms of inspiratory and expiratory
      muscle activation and the intrathoracic and intra-abdominal pressures generated
      are a reflection of the interaction between the various muscle groups. The Muller
      and sniff manoeuvres reflect mainly the force of the inspiratory muscles and the
      combined manoeuvre that of the diaphragm.

PMID- 8153918
TI  - Assessment and follow up of patients prescribed long term oxygen treatment.
AB  - BACKGROUND: Prescription and use of long term oxygen treatment were audited in a
      large group of patients after more than five years of use of the guidelines for
      its prescription. METHODS: Patients with a concentrator were interviewed at home
      with a structured questionnaire in three family health service authorities in
      East London. Stable oxygen saturation (SaO2) breathing air and oxygen, forced
      expiratory volume in one second (FEV1) and current and previous dated
      concentrator meter readings were recorded. A further questionnaire was sent to
      each patient's general practitioner. Hospital case notes of patients who did not
      meet the criteria for long term oxygen treatment at reassessment were reviewed.
      RESULTS: A total of 176 patients were studied; 84% had chronic obstructive lung
      disease and 19% admitted to continued smoking; 140 patients had seen a
      respiratory physician but results of respiratory assessment were available to
      their general practitioner in fewer than 54 cases. FEV1 was < 1.5 1 in 158
      patients but in 67 SaO2 was less than 91% breathing air, mainly in patients with
      chronic obstructive lung disease who had been inadequately assessed. Daily oxygen
      was prescribed for a median of 15 (range 4-24) hours and measured daily use was
      15 (0-24) hours; 74% of patients used more than 12 hours. Only 35 patients had
      problems with oxygen treatment, but 29 had an undercorrected SaO2 of less than
      92% when using their concentrator. CONCLUSIONS: Guidelines for prescription of
      long term oxygen treatment are largely followed and most patients complied with
      treatment. Increased communication about respiratory state is required between
      hospital doctors and general practitioners. Patients need regular reassessments
      to ensure that hypoxaemia is corrected and that oxygen is appropriately
      prescribed.

PMID- 8153919
TI  - Effect of alterations of dietary sodium on the severity of asthma in men.
AB  - BACKGROUND: There is some evidence of a positive association between increased
      dietary salt consumption and both increased bronchial reactivity and mortality
      from asthma in men. This study assesses the effects of alterations in dietary
      salt consumption on the clinical severity of asthma in adult male asthmatic
      patients. METHODS: A randomised, double blind, placebo controlled, crossover
      design was employed. Twenty seven mild to moderate asthmatic patients were
      established on a low sodium diet (80 mmol/day) at the end of a 4-5 day run in
      period and then randomised to receive 200 mmol/day slow sodium or matching
      placebo for five weeks, crossing over to the alternative regime for a further
      five weeks. Patients used diary cards to record twice daily peak expiratory flow
      rates, daily symptom scores, and bronchodilator consumption. Spirometry and
      degree of bronchial responsiveness (methacholine challenge test) were measured at
      screening and at the end of each treatment period. Twenty four hour urinary
      sodium excretion was measured at screening and in duplicate for each treatment
      period. RESULTS: Twenty two patients completed the study. For these patients the
      mean (95% confidence interval (CI)) difference in 24 hour sodium excretion
      between treatments was 204 (175 to 235) mmol. Compared with placebo, sodium
      supplementation resulted in deleterious alterations of all measured parameters.
      Bronchial reactivity rose on slow sodium with a 0.73 (0.2 to 1.3) doubling dose
      methacholine difference compared with placebo. Estimated median (95% CI)
      difference in bronchodilator consumption was 1.3 (0.4 to 2.1) puffs per day, the
      estimated median difference in symptom score was 0.6 (0.2 to 0.9), and mean
      forced expiratory volume in one second fell by 0.21 (0.05 to 0.37) 1. The peak
      expiratory flow rate rose on placebo and fell on slow sodium. Median differences
      between treatments were 5.6% (2.2% to 9.8%) for morning and 7.8% (3.9% to 12.9%)
      for evening peak expiratory flow rate. CONCLUSIONS: Our results suggest that
      large increases in dietary sodium result in physiological deterioration and
      increased morbidity in male asthmatic patients.

PMID- 8153920
TI  - Is the sleep apnoea/hypopnoea syndrome inherited?
AB  - BACKGROUND--The aetiology of the sleep apnoea/hypopnoea syndrome (SAHS) is
      unclear in many patients. Snoring, a prerequisite for SAHS, runs in families. A
      study was carried out to determine whether there is an increased frequency of
      irregular breathing during sleep in relatives of patients with SAHS. METHODS--A
      prospective study was performed of first degree relatives of 20 consecutive non
      obese (BMI < 30 kg/m2) patients with SAHS. Questionnaires on SAHS symptoms were
      sent to all first order relatives and those living within 150 miles of Edinburgh
      were invited for overnight monitoring of their breathing, sleep, and oxygenation
      patterns in the sleep laboratory. RESULTS--Ten of the 40 relatives had more than
      15 apnoeas + hypopnoeas/hour of sleep, and eight had more than five 4%
      desaturations/hour. These frequencies of irregular breathing and desaturation are
      significantly higher than in the British population. Cephalometric studies showed
      no skeletal abnormality but an increased uvular width was found in the affected
      relatives. CONCLUSIONS--There is an increased frequency of abnormal breathing
      during sleep in relatives of non-obese patients with SAHS.

PMID- 8153921
TI  - Variability of bronchodilator response and effects of inhaled corticosteroid
      treatment in obstructive airways disease. Dutch CNSLD Study Group.
AB  - BACKGROUND: In the day to day care of obstructive airways diseases (asthma and
      chronic obstructive pulmonary disease) important decisions such as disease
      classification and choice of therapy are based on assessment of the
      bronchodilator response. However, surprisingly little is known of the long term
      course of the bronchodilator response in patients with obstructive airways
      disease. METHODS: Data from a multicentre trial were used in which 274 patients
      aged 18-60 years with airways obstruction were selected with PC20 < 8 mg/ml and
      FEV1 < 95% CI of predicted. FEV1 was measured before and 20 minutes after 1000
      micrograms terbutaline and 40 minutes after an additional 80 micrograms
      ipratropium bromide. Data were analysed from 185 patients who were followed up
      for 21 months (five measurements). Four different expressions of bronchodilator
      response (BDR) were examined for change under long term therapy, long term
      variability, and prognostic value in predicting response to inhaled
      corticosteroids. RESULTS: There was a significant reduction in BDR of 117 ml
      after three months of treatment with a beta 2 agonist plus a corticosteroid (BA +
      CS), but not after bronchodilators only. Significant reductions with BA + CS were
      also found in BDR as a percentage of initial FEV1, and in BDR as a percentage of
      predicted FEV1. Bronchodilator tests were quite variable (SD 186 ml or 11% of
      initial value) and less than half of the patients could consistently be
      classified as "irreversible" with recommended cutoff levels. The bronchodilator
      response at the start of the study proved to be a poor predictor of improvement
      in FEV1 under BA + CS treatment (correct prediction 60%). CONCLUSIONS:
      Bronchodilator responses decrease substantially with inhaled corticosteroid
      therapy, and within subject variability is considerable both in asthma and
      chronic obstructive pulmonary disease. Dichotomous decisions on whether patients
      are "irreversible" according to any single bronchodilator measurement should
      therefore be made with great caution. The bronchodilator response cannot be used
      accurately as a predictor of response to inhaled corticosteroids in obstructive
      airways disease.

PMID- 8153922
TI  - Atrial natriuretic peptide in stable and decompensated chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Plasma levels of atrial natriuretic peptide (ANP) are elevated in
      patients with chronic obstructive pulmonary disease (COPD) and may have a role in
      preventing oedema formation in these patients. METHODS: Plasma ANP levels were
      measured in 60 patients with COPD and these measurements were related to
      pulmonary haemodynamics, response to treatment during exacerbations, and clinical
      patterns of the stable disease. RESULTS: Plasma ANP levels did not correlate
      significantly with right atrial or pulmonary arterial pressures but did correlate
      significantly with both the right ventricular end diastolic volume and right
      ventricular wall volume measured by magnetic resonance imaging. Oxygen (2 1/min
      by nasal prongs for 30 minutes) did not change the mean pulmonary arterial
      pressure or the level of plasma ANP. In 20 patients with an acute exacerbation of
      COPD plasma ANP levels were higher in those with oedema (302 (185) pg/ml) than in
      those without oedema (87 (43) pg/ml). Oxygen given for one hour had no effect on
      plasma levels of ANP. However, plasma ANP levels fell over the first three days
      during treatment in those with oedema, the fall correlating with the change in
      body weight. In a further 20 stable patients with hypoxic COPD, those with
      hypercapnia and previous episodes of oedema had higher levels of plasma ANP (120
      (50) pg/ml) than normocapnic patients with no previous oedema (54 (15) pg/ml).
      CONCLUSIONS: The level of ANP is high in the plasma of patients with COPD,
      particularly during exacerbations in those with oedema. The association of a high
      plasma ANP level and volume overload is shown by the fall in ANP levels with
      treatment of the oedema, and the correlation between levels of ANP and right
      ventricular end diastolic or wall volumes.

PMID- 8153923
TI  - Fibroblast chemotactic response elicited by native bronchoalveolar lavage fluid
      from patients with fibrosing alveolitis.
AB  - BACKGROUND: In fibrosing alveolitis activation of lung fibroblasts is the
      decisive event in the pathogenetic sequence leading to pulmonary fibrosis.
      Fibroblast stimulating activity was measured in bronchoalveolar lavage (BAL)
      fluid to assess its relationship to the activity of fibrosing alveolitis.
      METHODS: Nine control subjects and 40 patients with fibrosing alveolitis caused
      by idiopathic pulmonary fibrosis (n = 22) or pulmonary involvement in systemic
      sclerosis (n = 18) were studied. All patients were followed up by lung function
      testing for a minimum of six months (mean (SE) 13.3 (1.4) months). Twenty five
      patients received immunosuppressive therapy and 15 refused. At the beginning of
      follow up BAL was performed and, as a possible indicator of fibroblast
      stimulating mediators within the lungs, chemotactic migration of cultured human
      fibroblasts elicited by native BAL fluid was measured in Boyden-type chambers and
      expressed as a percentage of the chemoattractant effect of 25 ng/ml platelet
      derived growth factor. The procollagen III peptide level in BAL fluid served as a
      marker for collagen synthesis. RESULTS: Chemoattractant activity was elevated in
      the patients with idiopathic pulmonary fibrosis and systemic sclerosis compared
      with the control group, (mean (SE) 56.4% (8.5%)) and 72.3% (16.3%) v 12.6%
      (4.0%). Chemoattractant activity was inversely correlated with total lung
      capacity (TLC) (r = -0.45) and with vital capacity (VC) (r = -0.33). Procollagen
      III peptide concentrations in BAL fluid and chemoattractant activity were not
      significantly correlated. For further evaluation chemoattractant activity of 36%
      (mean value of controls +2 SD) was used to separate normal (< 36%) from elevated
      (> or = 36%) activity. At the end of follow up, untreated patients with high
      chemoattractant activity (> or = 36%) showed a significant reduction of VC, TLC,
      and exercise arterial oxygen tension (PaO2) and a small decrease in carbon
      monoxide transfer factor (TLCO), whereas a significant improvement in VC, TLC,
      and TLCO and a small increase of exercise PaO2 occurred in treated patients with
      high chemoattractant activity. Patients with low chemoattractant activity (< 36%)
      showed no consistent change in lung function measurements, irrespective of
      treatment. In contrast, lung function results and differential cell counts in BAL
      fluid failed to identify progressive disease. CONCLUSIONS: In patients with
      fibrosing alveolitis the chemoattractant activity of BAL fluid seems to be an
      independent indicator of lung fibroblast stimulating activity providing relevant
      information about disease activity, and may help to improve the clinical
      management of these patients.

PMID- 8153924
TI  - Arachnoid nodules in the lungs of high altitude Indians.
AB  - BACKGROUND: Nodules of cells showing a striking histological similarity to those
      of arachnoid villi have previously been found closely adjacent to pulmonary
      venules in several diseases associated with alveolar hypoxia or pulmonary oedema
      including mitral stenosis, plexogenic pulmonary arteriopathy, pulmonary
      thromboembolism, and chronic obstructive pulmonary disease. METHODS: Histological
      sections of the lungs of seven adult native highlanders from La Paz (3600 m) were
      examined. RESULTS: Arachnoid nodules were found in the lungs of one Aymara and
      one Mestizo Indian. CONCLUSIONS: These bodies may have a similar function to that
      of arachnoid granulations which transfer excess cerebrospinal fluid to the dural
      venous sinuses. In the native highlanders it is possible that they contribute to
      the avoidance of excessive hydration of the interstitial tissue of the alveolar
      walls with return of fluid into the pulmonary venules, preventing incipient
      pulmonary oedema.

PMID- 8153925
TI  - Association of silicosis, lung dysfunction, and emphysema in gold miners.
AB  - BACKGROUND: In an earlier study of gold miners men with silicosis were found to
      have abnormal lung function, including airflow obstruction and reduced diffusing
      capacity. In a follow up study a sample of these men was examined by computed
      tomography to determine whether emphysema accounted for these abnormalities,
      which are associated with silicosis in this working population. METHODS: A sample
      of 70 men from a cohort of older gold miners with and without silicosis who had
      worked underground for a mean period of 29 years was examined by computed
      tomography to determine whether each man had emphysema. In addition, each man had
      lung function tests and routine chest radiography (125 kV). RESULTS: A total of
      48 men had emphysema on examination by computed tomography. On the basis of the
      results in a chest radiograph 55 of the men had silicosis. Emphysema was related
      to silicosis, being present in five of the 15 men without silicosis and in 43 of
      the 55 with silicosis. Diffuse emphysema was apparent in two men without
      silicosis (14%) and in 25 men with silicosis (45%). The proportion of men with
      diffuse emphysema increased from 14% in those with International Labour
      Organisation category 0 nodule profusion to 46% in those with category 1, 48% in
      those with category 2, and 67% in those with category 3. Emphysema was also
      related to smoking: eight of the 18 who had never smoked and 40 of the 52 smokers
      had emphysema. All of those who had never smoked and had emphysema had silicosis
      with category 2/2 or greater nodule profusion. Lung function tests showed changes
      associated with silicosis that could be explained by the associated emphysema.
      CONCLUSIONS: In this population emphysema occurred in association with silicosis
      and accounted for the abnormalities in lung function associated with silicosis.

PMID- 8153926
TI  - Normal range for transdiaphragmatic pressures during sniffs with catheter mounted
      transducers.
AB  - BACKGROUND: Transdiaphragmatic pressure (sniff PDI) during maximal sniffs is a
      useful clinical test of inspiratory muscle function. Although a normal range has
      been established for sniff PDI using air filled balloons, no comparable data are
      available for catheter mounted pressure transducers. METHODS: Using a single
      catheter with two pressure transducers 15 cm apart, oesophageal and gastric
      pressures were recorded in 50 normal volunteers (25 women), five of each sex from
      each decade between the third and seventh decades of life. Each subject performed
      10 maximal sniffs at functional residual capacity. RESULTS: Mean (SD) sniff PDI
      was 149 (32) cm H2O in men and 127 (22) cm H2O in women. The lower limits of
      normal for sniff PDI (mean -1.96 x SD) after logarithmic transformation of the
      data were 95 and 78 cm H2O in men and women respectively. CONCLUSIONS: With this
      technique transdiaphragmatic pressure can be measured using a single catheter
      which can easily be cleaned and reused. The values for sniff PDI are similar to
      those recorded previously with air filled balloons, suggesting that the method of
      recording pressure does not significantly affect the values obtained.

PMID- 8153927
TI  - Obstructive sleep apnoea.

PMID- 8153929
TI  - Ciliary disorientation: a possible variant of primary ciliary dyskinesia.
AB  - Random ciliary orientation has recently been proposed as a variant of primary
      ciliary dyskinesia. We report a 12 year old boy with all the features of primary
      ciliary dyskinesia and absent nasal mucociliary clearance in whom repeated
      biopsies of the nasal epithelium showed normal ciliary beat frequency. The only
      abnormality discovered was disorientation of the central microtubules of his
      cilia.

PMID- 8153928
TI  - Cytokines. 2. Cytokines and lung inflammation: mechanisms of neutrophil
      recruitment to the lung.

PMID- 8153930
TI  - Oesophageal tuberculosis mimicking a tumour during treatment for nodal
      tuberculosis.
AB  - A patient with cervical lymph node tuberculosis developed a tubercular ulcer in
      the oesophagus eight weeks after starting treatment. This was probably due to a
      drug related hypersensitivity reaction in an adjacent mediastinal lymph node and
      subsided with continued treatment.

PMID- 8153931
TI  - Asthma following occupational exposure to Lycopodium clavatum in condom
      manufacturers.
AB  - Occupational asthma in two women employed in the manufacture of condoms is
      reported. The spores of Lycopodium clavatum, used as a rubber dusting agent, were
      identified as the causative agent.

PMID- 8153932
TI  - Sex differences in hypokalaemic and electrocardiographic effects of inhaled
      terbutaline.

PMID- 8153933
TI  - Preoperative screening for metastases in lung cancer.

PMID- 8153935
TI  - Surgical resection for small cell carcinoma of the lung: a retrospective study.
AB  - BACKGROUND: A retrospective review was undertaken of the survival of 21 patients
      with histologically proven small cell carcinoma of the lung resected between 1977
      and 1991. METHODS: Twenty one patients (20 men) of median age 60 (range 44-73)
      years underwent surgical resection. Patients were subjected to standard clinical
      staging procedures. Preoperative diagnosis was small cell carcinoma of the lung
      in 13, non-small cell lung cancer in one, and uncertain in seven patients.
      Clinical staging was stage I disease in 11 and stage II in 10 patients. RESULTS:
      Resection included pneumonectomy in 12 cases, lobectomy in eight, and one wedge
      resection. Resection was complete in 16 patients. Postoperative histopathological
      examination confirmed small cell carcinoma of the lung in 19 specimens and mixed
      small cell and non-small cell carcinoma of the lung in two. Pathological staging
      was stage I in 11, stage II in three, and stage III in seven patients. The final
      pathological diagnosis of the resected specimens (n = 18) was atypical carcinoid
      in one, pure small cell carcinoma of the lung in 15, and mixed small cell and non
      small cell carcinoma of the lung in two patients. Fourteen patients also received
      chemotherapy and 10 received prophylactic cranial irradiation postoperatively.
      Excluding the patient with a final diagnosis of atypical carcinoid, the median
      survival (n = 20) was 29 months (range two to 133+). Median survival for patients
      with pathological stage I and II disease (n = 13) was 40 months (range nine to
      133+) and for patients with pathological stage III disease (n = 7) 20 months
      (range two to 116+). The median disease free survival was 23 months. Eleven
      patients relapsed between two and 101 months. There was no advantage for those
      patients who received postoperative chemotherapy. CONCLUSION: Curative resection
      offers the best chance for long term survival in patients with small cell
      carcinoma of the lung with very limited stage disease.

PMID- 8153934
TI  - Analysis of published studies on the detection of extrathoracic metastases in
      patients presumed to have operable non-small cell lung cancer.
AB  - BACKGROUND: A study was undertaken to determine the proportion of patients with
      potentially operable non-small cell lung cancer that could be spared thoracotomy
      by a systematic search for extrathoracic metastases. METHODS: An English language
      literature search was carried out using MEDLINE (1966-91) and bibliographic
      reviews of textbooks, review articles, and key articles. Studies were included in
      which at least 90% of the patients had histologically proven non-small cell
      cancer of the lung, were presumed otherwise operable, and for which the results
      of computed tomography of the head or abdomen, ultrasonography of the abdomen, or
      radionuclide imaging (scan) of bone or liver were available. Study quality and
      specific descriptive information concerning population, intervention, and outcome
      measurements were assessed. RESULTS: Of approximately 1500 citations which were
      screened, 100 were reviewed in detail and data abstracted from 16. The number of
      patients (total number, followed in square brackets by number of asymptomatic
      patients) shown to be inoperable directly as a result of the investigation and
      thus spared unnecessary thoracotomy was: computed tomography of the head: 26/785
      (3.3%), 95% confidence interval (CI) 2.1% to 4.4% [14/353 (4.0%), 95% CI 2% to
      6%], computed tomography of the adrenal glands: 30/632 (4.7%), 95% CI 3.0% to
      6.4% [number asymptomatic indeterminate], bone scan: 45/480 (9.3%), 95% CI 6.7%
      to 12% [9/301 (3.0%), 95% CI 1.1% to 4.9%], liver imaging: 12/529 (2.3%), 95% CI
      0.9% to 3.3% [4/268 (1.5%), 95% CI 0.1% to 3%]. CONCLUSIONS: A study with a large
      sample size and preferably incorporating thoracic computed tomography is required
      to narrow the confidence intervals around each test. All tests may play an
      important part in the preoperative evaluation of patients with non-small cell
      carcinoma of the lung who are presumed to be operable, including asymptomatic
      patients. Limitations of present data preclude definitive recommendations for
      asymptomatic patients.

PMID- 8153936
TI  - Peripheral mononuclear leucocyte beta adrenoceptors and non-specific bronchial
      responsiveness to methacholine in young and elderly normal subjects and asthmatic
      patients.
AB  - BACKGROUND: As beta adrenoceptor dysfunction occurs in both the normal elderly
      subject and in young asthmatic patients, the hypothesis was examined that age
      related beta adrenoceptor changes are important in the pathogenesis of late onset
      asthma in old age. METHODS: Subjects were non-smokers who comprised 17 young
      normal subjects of mean (SE) age 29.4 (1.3) years, 17 elderly normal subjects of
      67.2 (1.3) years, seven young asthmatic patients of 31.0 (2.8) years, and 17
      elderly asthmatic patients of 68.5 (1.4) years. All asthmatic patients withheld
      inhalers for 12 hours and oral treatment for 24 hours before each study day.
      Subjects underwent an inhaled methacholine challenge (Newcastle dosimeter method)
      on two nonconsecutive days. The slope of the flow at 50% of the vital capacity
      (FEF50) dose-response curve was derived from the percentage fall in FEE50 divided
      by methacholine dose (sFEF50). Beta-adrenoceptor density (Bmax) and affinity
      (%KH) were determined with (125I)iodocyanopindolol as the radioligand in
      membranes prepared from mononuclear leucocytes. RESULTS: Log sFEF50 was shown to
      be reproducible (repeatability coefficient 0.41) on the two study days and was
      inversely related to %KH but not to Bmax. Multiple regression analysis (all 58
      subjects, overall R2 = 0.57) revealed an inverse relation between log sFEF50 and
      %KH, and between log sFEF50 and Bmax. The inverse relation between log sFEF50 and
      %KH was preserved whereas that between log sFEF50 and Bmax was lost when young
      asthmatic subjects or when all asthmatic subjects were excluded from multiple
      regression analysis. CONCLUSIONS: The beta adrenoceptor dysfunction observed in
      late onset asthma may be similar to that seen during ageing. Thus late onset
      asthma may represent the extreme of a spectrum of age associated beta
      adrenoceptor dysfunction.

PMID- 8153938
TI  - Risk factors for readmission to hospital for asthma in childhood.
AB  - BACKGROUND: Readmissions account for part of the increase in hospital admissions
      for asthma in childhood seen in many countries. METHODS: This observational study
      recorded demographic features and the severity, treatment and management of
      asthma in 1034 individual children admitted to hospital over a one year period,
      followed for a maximum of 33 months. RESULTS: Readmissions were common, with 33%
      readmitted by six months and 51% by two years. After controlling for a wide range
      of variables, factors that significantly increased readmission were: female sex
      (relative risk (RR) 1.23; 95% confidence interval (CI) 1.03 to 1.46), young age
      (age < 5 years RR 1.71; 95% CI 1.41 to 2.08), number of previous admissions (one
      previous admission RR 1.32; two, RR 1.68; three, RR 2.00; four or more, RR 2.80),
      and inpatient intravenous treatment (RR 1.29; 95% CI 1.08 to 1.55). Inpatient
      treatment with theophylline was used frequently (98.4%), but was associated with
      decreased readmissions (RR 0.51, 95% CI 0.28 to 0.92). Factors which did not
      predict readmission included ethnicity, respiratory and pulse rate, medical team,
      prescribed prophylactic treatment, type of follow up, or the use of action plans.
      CONCLUSIONS: Risk factors for readmission relate to the characteristics of the
      individual (age and sex), severity of the condition (intravenous treatment), and
      number of previous admissions which may reflect severity or behaviour of the
      illness. Medical treatment and management did not influence readmissions.
      Strategies to reduce the high readmission rate for asthma in childhood need to be
      developed.

PMID- 8153937
TI  - Use of bronchoscopy in the diagnosis of infection in the immunocompromised host.

PMID- 8153940
TI  - Influence of barn drying of fodder on respiratory symptoms and function in dairy
      farmers of the Doubs region of France.
AB  - BACKGROUND: A previous study showed there to be fewer microorganisms (especially
      thermophilic actinomycetes) on farms with artificial barn drying of fodder than
      on those using traditional storage methods. A cross sectional study was performed
      to see whether barn drying provides protection against respiratory problems in
      dairy farmers. METHODS: The respiratory symptoms and function of a group of 123
      farmers with daily exposure to cattle foddering from farms which had had a barn
      drying system for at least three years were compared with those of a
      representative sample of 274 farmers working in farms with traditional storage in
      five districts in the Doubs region of France. RESULTS: Both groups were
      comparable for mean age, weight, height, smoking habits, alcohol consumption,
      past history of respiratory disease, history of allergy, geographical location of
      the farm, and length of exposure. Retrospectively estimated exposure to fodder
      was greater in the group using a barn drying system than in the group working
      with traditional storage. Acute symptoms at exposure (rhinitis, eye irritation,
      dry cough, asthma symptoms) and chronic symptoms all tended to be less frequent
      in the barn drying group, although not individually significantly so. Mean (SD)
      respiratory function parameters were higher in the barn drying group than in the
      traditional group: % vital capacity (VC) 104 (14) v 102 (15); % forced expiratory
      volume in one second (FEV1) 99 (14) v 94 (18); % FEV1/VC 96 (11) v 92 (16); %
      forced mid expiratory flow (FEF25-75) 87 (24) v 79 (25). CONCLUSION: The results
      of this cross sectional study suggest that barn drying of fodder may protect
      respiratory function in dairy farmers.

PMID- 8153939
TI  - Comparison of inhaled beclomethasone dipropionate 1000 micrograms twice daily and
      oral prednisone 10 mg once daily in asthmatic patients.
AB  - BACKGROUND: Glucocorticosteroids are widely used as drugs of first choice in the
      treatment of moderate to severe asthma. The effects of inhaled steroids in high
      doses have been compared with oral prednisone in asthmatic patients in a double
      blind crossover study. METHODS: The trial consisted of a two week run in period
      followed by two four week treatment periods separated by a four week washout.
      During the treatment period patients took either 1000 micrograms beclomethasone
      dipropionate twice daily and placebo tablets once daily, or 10 mg prednisone
      daily in one morning dose and placebo inhaler twice daily. The effects of
      treatment on the provocative dose of histamine producing a 20% fall in FEV1 (PC20
      histamine), peak flow measurements at home, and spirometric measurements in the
      clinic, as well as on the basal and stimulated plasma cortisol levels were
      measured. RESULTS: Seventeen patients with asthma completed the study. After four
      weeks of treatment beclomethasone dipropionate showed a significantly better
      effect on morning peak expiratory flow rate than prednisone. There was a trend to
      a greater improvement in the PC20 histamine in patients receiving beclomethasone
      dipropionate than in those receiving prednisone. There were no significant
      differences in spirometric values, symptom scores, or basal and stimulated
      cortisol levels between the treatments. The within treatment analysis showed a
      significant effect of prednisone on stimulated cortisol levels but not of
      beclomethasone dipropionate. CONCLUSIONS: Beclomethasone dipropionate 1000
      micrograms twice daily has a slightly greater therapeutic effect in this
      population of asthmatic patients than 10 mg of prednisone once a day with less
      effect on adrenocortical function.

PMID- 8153941
TI  - Maximum relaxation rate of the diaphragm during weaning from mechanical
      ventilation.
AB  - BACKGROUND: The maximum relaxation rate (MRR; percentage fall in pressure/10 ms)
      of oesophageal (POES) and transdiaphragmatic (PDI) pressure slows under
      conditions of loaded breathing, and has been measured previously in normal
      subjects. MRR has not been measured in intubated patients weaning from mechanical
      ventilation. METHODS: Five postoperative patients who were expected to wean and
      nine patients who had previously failed were studied. POES and PDI MRR, peak
      oesophageal pressure during spontaneous breathing, maximum oesophageal pressure,
      and the inspiratory duty cycle were measured at rest during mechanical
      ventilation, in the first two minutes of spontaneous breathing, and after
      reventilation in those patients who failed, or before extubation in those
      patients who succeeded. RESULTS: At rest POES MRR in intubated patients had a
      range of 5.6-11 and PDI MRR 6.9-10.0, with a coefficient of variation of 9.9% and
      7.3% respectively. POES and PDI MRR were similar before and after extubation in
      five postoperative patients, and POES MRR was reflected by endotracheal MRR
      measured at the airway. In five patients who failed to wean POES and PDI MRR
      slowed by 47% and 44%, and fully recovered after 10 minutes reventilation. In
      four patients who were successfully weaned MRR was unchanged during spontaneous
      breathing. At the time when MRR decreased, the respiratory muscles were heavily
      loaded in relation to their strength. CONCLUSIONS: Weaning failure occurs when
      the applied load exceeds the capacity of the respiratory muscles, and this is
      associated with a slowing of respiratory muscle MRR.

PMID- 8153942
TI  - Lung and respiratory muscle function in limb girdle muscular dystrophy.
AB  - BACKGROUND: Pulmonary involvement is frequently observed in patients with limb
      girdle muscular dystrophy and occurs early in the disease. The aim of this study
      was to establish the prevalence of pulmonary dysfunction; the type of
      dysfunction; and any correlation between patient age, disease duration, or limb
      weakness and lung or respiratory muscle dysfunction. METHODS: Twenty patients
      with strictly delineated limb girdle muscular dystrophy and 20 healthy controls
      were evaluated. Full inspiration chest radiographs were obtained. Standard lung
      and respiratory muscle function tests were performed and the data were
      statistically analysed. RESULTS: The mean age of the patients was 40.6 years, the
      mean disease duration was 18.9 years, and the mean average muscle score (a
      numerical expression of limb weakness) was 5.73 out of 10. Chest radiography
      showed unilateral paresis of the diaphragm in three patients. Increased residual
      volumes, with either increased or decreased total lung capacity, correlated
      inversely with disease duration. Respiratory muscle weakness was common but mild.
      Expiratory muscle function was more impaired than inspiratory muscle function and
      correlated positively with expiratory reserve volume. CONCLUSIONS: Respiratory
      muscle strength is commonly impaired in limb girdle muscle dystrophy. A
      dissociation of the limb and mild respiratory muscle involvement is observed;
      wheelchair restriction does not predict worsening of pulmonary function, and
      patient age, disease duration, or degree of limb weakness do not predict
      pulmonary morbidity. The diaphragm is not disproportionately affected by the
      dystrophic process compared with limb muscles.

PMID- 8153943
TI  - Sleep hypoxia in myotonic dystrophy and its correlation with awake respiratory
      function.
AB  - BACKGROUND: Tiredness and daytime respiratory failure occur frequently in
      myotonic dystrophy. Sleep hypoxaemia was studied in 12 patients with myotonic
      dystrophy and correlations were sought with their daytime lung and respiratory
      muscle function. METHODS: All patients underwent overnight sleep studies,
      clinical assessment, measurement of flow-volume loops and carbon monoxide
      transfer factor, arterial blood gas analysis, and physiological assessment of
      both thoracic muscle function and upper airways obstruction. RESULTS: The mean
      nadir of oxygen saturation during sleep was 75% (95% confidence interval 69% to
      81%). A mean of 3.4% of total sleep duration was spent at an oxygen saturation
      level below 85%. Five of the 12 patients had an apnoea index of > 5, the group
      mean apnoea/hypopnoea index being 15.8 events/sleep hour. The mean awake arterial
      oxygen tension (PaO2) was 10.7 kPa. There was a trend to hypercapnoea with a mean
      awake arterial carbon dioxide tension of 6.1 kPa; carbon dioxide retention
      worsened during sleep. Respiratory muscle dysfunction was mainly evident as a low
      maximum expiratory mouth pressure. Upper airway obstruction assessed by
      physiological criteria was found in four of the 12 patients. The proportion of
      total sleep duration with oxygen saturation levels below 85% was directly related
      to body mass index (weight/height2) and inversely related to the awake PaO2. Body
      mass index was inversely related to the overnight nadir of oxygen saturation.
      CONCLUSIONS: Patients with myotonic dystrophy are often hypoxic during sleep and
      the subgroup that are obese, or have symptoms of sleep apnoea, or both, are
      particularly at risk. Sleep studies should be considered in this subgroup of
      patients with myotonic dystrophy.

PMID- 8153944
TI  - Re-evaluation of pneumonia requiring admission to an intensive care unit: a
      prospective study.
AB  - BACKGROUND: Appropriate treatment of severe community and hospital acquired
      pneumonias requiring admission to a medical intensive care unit depends on
      knowledge of the likely aetiological agents in any community. Little is known
      about the pattern and outcome of patients with such pneumonias in Saudi Arabia.
      METHODS: In a prospective study 113 patients with pneumonia were investigated in
      the medical intensive care unit at King Khalid University Hospital, Riyadh, Saudi
      Arabia between September 1991 and December 1992. The diagnosis was established by
      microscopy and culture of sputum, blood culture, or serological examination. A
      standard proforma was used to collect demographic, clinical, and laboratory data.
      RESULTS: A microbiological diagnosis was made in 80% of the cases with a single
      pathogen accounting for 69% of the isolates and multiple pathogens for 11%.
      Pseudomonas aeruginosa was the most common infecting agent (16%), followed by
      Streptococcus pneumoniae (12%), Staphylococcus aureus (9%), and Mycobacterium
      tuberculosis (8%). Pneumonia due to Legionella pneumophilia was diagnosed in
      three patients and infection due to Mycoplasma pneumoniae in two. These five
      cases were identified by serological examination. Gram negative rods were the
      predominant pathogens in both community and hospital acquired pneumonia. The
      aetiology of pneumonia was not identified in 20% of cases. The overall mortality
      was 37%. Patients with hospital acquired pneumonia had a higher mortality than
      those with a community acquired pneumonia. Similarly, a high mortality was found
      in patients who had a serious underlying disease, abnormal mental state,
      diastolic blood pressure < 60 mm Hg, blood urea > 7 mmol/l, abnormal liver
      function tests, serum albumin < 30 g/l, those who required mechanical ventilatory
      support, and those with APACHE II scores > 20. CONCLUSIONS: This study highlights
      two major findings which differ from previous reports on the aetiology of
      pneumonia. Firstly, Gram negative rods were the predominant pathogens in
      community acquired pneumonia and secondly, M tuberculosis was an important cause
      of pneumonia in these patients, indicating that tuberculous pneumonia should be
      considered in the differential diagnosis of pneumonia in Saudi Arabia.

PMID- 8153945
TI  - Pulmonary rehabilitation in chronic respiratory insufficiency. 6. Travel for
      technology-dependent patients with respiratory disease.

PMID- 8153946
TI  - Sequelae of the adult respiratory distress syndrome.
AB  - Most survivors of ARDS have persistent mild reductions of TLCO even as long as a
      year after their episode. The lung volumes and flows return to normal in most
      instances, although a subset of patients will have persistent impairment. Both
      obstructive and restrictive deficits may be seen. This group may be predicted by
      the degree of acute lung injury assessed by the level of FIO2, PEEP, and gas
      exchange abnormality that exists in the first few days. In the first year after
      ARDS most physiological abnormalities will improve, but if deficits persist at
      one year further improvement is unlikely. Although many patients report dyspnoea
      following ARDS, the symptom does not correlate with abnormalities of pulmonary
      function. The possibility that conventional management may augment the degree of
      acute injury and worsen outcome must be considered. The effects of chronic
      hyperoxia in humans with acute lung injury or those of high levels of PEEP
      compared with low levels are not known. Exploring new ventilator management
      strategies while we await more specific treatment directed at the primary problem
      of acute lung inflammation will hopefully reduce acute mortality as well as acute
      and chronic morbidity.

PMID- 8153947
TI  - Correction of the single breath carbon monoxide transfer factor in exercise for
      variations in alveolar oxygen pressure.
AB  - BACKGROUND: Carbon monoxide transfer factor (TLCO) varies inversely with the
      partial pressure of alveolar oxygen (PAO2). During exercise the PAO2 in the
      alveolar gas sample bag decreases so the TLCO increases more than would be
      expected from the effects of exercise alone. The effects of PAO2 on the
      estimation of TLCO during exercise have been investigated and studies have been
      performed to determine whether it is appropriate to standardise to a PAO2 of 16
      kPa. METHODS: TLCO was estimated at rest and at a single level of exercise in six
      normal subjects using test gas mixtures of 0.3% carbon monoxide, 14% helium, and
      oxygen in three different percentages (17%, 21%, and 27%), remainder nitrogen. In
      three of the subjects an incremental exercise test with estimates of oxygen
      consumption (VO2) and cardiac frequency (fC) was also performed using a mixture
      containing 18% oxygen. RESULTS: TLCO decreased as levels of inspired oxygen
      increased. When standardised to a PAO2 of 16 kPa TLCO became independent of the
      inspired oxygen concentration. The significance of the curvilinear relations of
      TLCO and transfer coefficient to VO2 and fC improved. CONCLUSION: The single
      breath breath holding TLCO should be standardised to a PAO2 of 16 kPa when
      estimated during exercise.

PMID- 8153948
TI  - Tracheal schwannoma: management by endoscopic laser resection.
AB  - The case history is presented of a patient with a tracheal schwannoma who remains
      free of disease five and a half years after laser resection. This illustrates the
      potential of this approach in the management of tracheal schwannoma.

PMID- 8153949
TI  - Pleural fluid characteristics in pulmonary brucellosis.
AB  - Although pulmonary symptoms accompany up to 16% of cases of infection with
      Brucella melitensis, pleural effusion has rarely been reported. A 12 year old
      girl had brucellosis with pulmonary disease and a pleural effusion. The pleural
      fluid was clear and straw coloured with 2700 leucocytes/mm3 (93% lymphocytes), a
      protein level of 48 g/1, and a glucose concentration of 4.1 mmol/l. Culture of
      the pleural fluid grew Br melitensis.

PMID- 8153950
TI  - Response to ketamine in status asthmaticus resistant to maximal medical
      treatment.
AB  - The case is reported of a 28 year old woman with status asthmaticus unresponsive
      to three days of maximal medical treatment. Resolution of bronchospasm was
      achieved with an infusion of the intravenous anaesthetic agent ketamine.

PMID- 8153951
TI  - Pancoast syndrome caused by a high grade B cell lymphoma.

PMID- 8153953
TI  - 23rd Annual meeting of the German Society for Thoracic and Cardiovascular
      Surgery. Bonn, February 16-19, 1994. Abstracts.

PMID- 8153954
TI  - Poisonous plants of Brazil.
AB  - Poisonous plants are a serious problem for cattle breeding in Latin America.
      Owing to the extensive pastural agriculture it is not possible to exterminate
      such plants. Apart from the considerable financial loss to individual farmers and
      the national economy owing to dead animals, there is the important question of
      how far the meat and milk of chronically poisoned animals are a health risk for
      humans. The toxins of the most important toxic plants from Brazil are described.

PMID- 8153952
TI  - Familial predisposition to snoring.

PMID- 8153955
TI  - Purification by HPLC anion-exchange chromatography and some properties of a kinin
      releasing enzyme from the venom of Agkistrodon halys ussuriensis.
AB  - A kinin-releasing enzyme was isolated from the venom of Agkistrodon halys
      ussuriensis using a very convenient two-step procedure consisting of HPLC anion
      exchange chromatography. The relative molecular mass was estimated as 24,000 by
      SDS gel electrophoresis and an isoelectric point of pH 3.7 was established by gel
      isoelectric focusing. The kinin-releasing enzyme resembled a typical tissue
      kallikrein in the values of such physiochemical parameters, in its thermal
      stability, in its lack of activity towards fibrinogen and casein, and in its
      behaviour with potential inhibitors. Thus, the enzyme can be classified as a
      kallikrein-like enzyme.

PMID- 8153956
TI  - Occurrence of carbamoyl-N-hydroxy derivatives of saxitoxin and neosaxitoxin in a
      xanthid crab Zosimus aeneus.
AB  - Two novel paralytic toxins were isolated from toxic specimens of a xanthid crab
      Zosimus aeneus inhabiting Ishigaki Island, Okinawa. The structures of two of
      these were deduced to be carbamoyl-N-hydroxysaxitoxin and carbamoyl-N
      hydroxyneosaxitoxin based on electrophoresis, high performance liquid
      chromatography, electrospray ionization mass spectrometry, 1H NMR, 13C NMR and
      conversion experiments. They showed specific toxicities of 1700 and 1400 mouse
      units per mg on i.p. injection into mice.

PMID- 8153957
TI  - A new antivenom to treat eastern coral snake (Micrurus fulvius fulvius)
      envenoming.
AB  - An Fab based ovine antivenom has been prepared and compared both in vitro and in
      vivo with two commercial preparations. The product was found to be at least four
      times more effective on a weight basis. The increased potency, combined with the
      low incidence of side-effects associated with ovine Fab, should result in a
      safer, more effective antivenom.

PMID- 8153958
TI  - Cardiovascular effects of Buthus martensii (Karsch) scorpion venom.
AB  - Buthus martensii (Karsch) (BMK) scorpion envenomation is a common medical problem
      in China and BMK scorpion has been widely used in traditional Chinese medicine.
      However, the cardiovascular effects of this venom have not been systematically
      investigated. In the present study, i.v. BMK venom injection significantly
      increased the blood pressure in conscious rats in a concentration-dependent
      manner (ED50 = 59 +/- 12 micrograms/kg). The increase in blood pressure occurred
      within 1 min of injection of the venom and was sustained for more than 50 min.
      Heart rate was not changed by the venom in conscious rats. In vitro studies with
      BMK venom revealed the increase in the force of contraction, without modification
      of the contraction frequency (within 20 min) of isolated atrial strips.
      Contractions of isolated arterial strips from aorta, renal and vertebral arteries
      were also enhanced by BMK venom with a time lag of 8 min between the application
      of the venom and the initiation of the contraction. Furthermore, BMK venom
      induced rises in blood pressure in vivo and increased contraction of isolated
      vessel strips were inhibited by prazosin and tolazoline, respectively, two alpha
      1-adrenergic antagonists. BMK venom alone did not alter intracellular calcium
      concentrations, [Ca2+]i, in cultured vascular smooth muscle cells and endothelial
      cells. However, BMK venom significantly increased the metabolism of InsP3 in
      dispersed cardiac myocytes, indicating a direct effect on cardiac myocytes. These
      results demonstrate the significant cardiovascular effects of BMK venom, which
      may be mediated by an alteration in InsP3 in cardiac myocytes but not by [Ca2+]i
      in vascular smooth muscle cells.

PMID- 8153959
TI  - Prejunctional action of the venom from the Indian red scorpion Mesobuthus tamulus
      on adrenergic transmission in vitro.
AB  - Venom (RSV) from the Indian red scorpion, Mesobuthus tamulus (Buthus tamulus),
      can cause increased peripheral sympathetic activity with consequent enhancement
      of adrenergic responses. We have therefore investigated the effects of RSV on
      adrenergic transmission in the rat isolated anococcygeus muscle. The effects of
      phentolamine (5 microM), tetrodotoxin (2 microM), guanethidine (5 microM),
      desipramine (1 microM) and reserpine pretreatment in vivo (5 mg/kg s.c. x 24 hr
      and 5 mg/kg i.p. x 3 hr) on the contractile responses of the rat anococcygeus
      muscle to RSV (1.5 microgram/ml), field stimulation, noradrenaline (NA, 1 microM
      or 3 microM) and tyramine (15 microM) were compared. The contractile responses to
      RSV and to field stimulation were completely blocked by phentolamine,
      tetrodotoxin, guanethidine and reserpine pretreatment, but the responses were
      potentiated by desipramine. The contractile responses to tyramine were completely
      blocked by phentolamine, reserpine pretreatment as well as desipramine. The
      responses to NA were completely blocked by phentolamine, but were potentiated by
      guanethidine, desipramine and reserpine. Relatively low concentrations (0.1
      microgram/ml x 4) of RSV which did not produce any observable increase in tone of
      the anococcygeus muscle, potentiated the contractile response of the anococcygeus
      muscle to field stimulation, but not the responses to exogenous NA; 4
      aminopyridine (25 microM x 2) also potentiated the muscle responses to field
      stimulation. HPLC measurements revealed only very low concentrations (0.10 +/-
      0.03 mumol/g venom) of NA in RSV. Thus, the adrenergic agonist action of RSV in
      the rat isolated anococcygeus muscle can be attributed to the involvement of some
      prejunctional mechanism(s) of action that stimulates the release of
      neurotransmitter which differs from the indirect action mediated by tyramine.

PMID- 8153960
TI  - Children with adrenergic manifestations of envenomation after Tityus serrulatus
      scorpion sting are protected from early anaphylactic antivenom reactions.
AB  - The incidence of early anaphylactic reactions to scorpion antivenom given i.v.
      after Tityus serrulatus scorpion sting was evaluated in 103 children aged up to
      15 years in Belo Horizonte, Brazil. Patients without adrenergic manifestations
      (Group 1, n = 28) were compared with those who presented systemic involvement
      that included adrenergic manifestations (Group 2, n = 75). Data were recorded on
      a proforma and the presence or absence of early anaphylactic reaction was cross
      tabulated according to clinical features, sex, age and volume of antivenom used
      in the treatment. Unpaired Student's t-test was used to calculate significance of
      differences in age and volume of antivenom used. Multivariate logistic regression
      was used to determine the effects of clinical features and volume of antivenom as
      predictors of early anaphylactic reaction to antivenom treatment. Twelve (42.9%)
      of 28 children included in Group 1 presented early anaphylactic reactions
      compared with 6 (8%) of 75 children of Group 2 (OR = 8.63; 95% CI: 2.88, 25.7).
      The reactions were more severe in Group 1. There were no significant differences
      with respect to age and sex. After adjusting for clinical form, volume of
      antivenom was not significantly associated with presence of reactions (OR = 1.11;
      95% CI: 0.70, 2.80 for each 5.0 ml of antivenom administered). The results show
      that children with adrenergic manifestations after T. serrulatus scorpion sting
      had significantly lower anaphylactic reactions to antivenom than those without
      these manifestations.

PMID- 8153961
TI  - Crotoxin induces aggregation of human washed platelets.
AB  - Crotoxin, the main toxic component isolated from the venom of the South American
      rattlesnake Crotalus durissus terrificus, is a reversible protein complex
      composed of a non-toxic non-enzymatic acidic polypeptide (crotapotin) and a toxic
      basic phospholipase A2 (PLA2). In this study, we have evaluated the ability of
      crotoxin to induced aggregation in human washed platelets. Human washed platelet
      aggregation was monitored in a Payton aggregometer and thromboxane B2 (TXB2)
      release measured by direct radioimmunoassay (RIA). Crotoxin (15-50 micrograms/ml)
      produced dose-dependent and irreversible human washed platelet aggregation, which
      was inhibited by pre-incubation of the platelets with sodium nitroprusside (50
      500 microM) or iloprost (8-80 nM). Crotoxin also induced TXB2 release (207 +/- 8
      ng/ml, n = 6), and although indomethacin significantly reduced the release of
      TXB2 (to 23.5 +/- 5 ng/ml, P < 0.001, n = 6), it did not inhibit crotoxin-induced
      aggregation. Our results clearly demonstrate that crotoxin induces human washed
      platelet aggregation and that this phenomenon is independent of the formation of
      pro-aggregatory arachidonic acid metabolites.

PMID- 8153962
TI  - Detection of alkaline phosphatase in venom by blotting methods.
AB  - Venom alkaline phosphatase was detected using a blotting method following
      electrophoresis. The enzyme gave strong reactions in some venoms, but was absent
      in other venoms, some within the same species. The mol. wt of the enzyme is close
      to 100,000 and its pI is between 3.6 and 4.8. The enzyme was inactivated by EDTA
      and 2-mercaptoethanol, and lost activity by freezing and thawing. Endogenous
      venom alkaline phosphatase can interfere with alkaline phosphatase-based
      detection methods. Pre-screening for endogenous venom alkaline phosphatase is
      recommended prior to using alkaline phosphatase-based detection methods when
      studying snake venom.

PMID- 8153963
TI  - Ageing and acetylcholine release by tityustoxin from brain cortical slices.
AB  - The ability of tityustoxin to trigger acetylcholine release was studied in
      cerebral cortical slices from 2, 12 and 23-month-old rats. The effect of
      tityustoxin to induce the release of acetylcholine was reduced by 60% in
      senescent animals. This result suggests that ageing reduces the sensitivity of
      cerebral cortical nerve terminals to tityustoxin.

PMID- 8153964
TI  - Worker-client exchanges and contraceptive use in rural Bangladesh.
AB  - In this article, longitudinal data from rural Bangladesh are used to assess the
      impact of household visits from family planning workers on contraceptive use. A
      panel of women was interviewed in a demographic survey and reinterviewed every 90
      days for six successive rounds. Regression methods are used to estimate the
      effect of these encounters on the odds that a woman will use contraceptives.
      Statistical controls adjust for the potentially confounding effects of underlying
      demand for contraception. Findings suggest that both male and female worker
      initiated exchanges have an effect, although the impact of outreach is more
      pronounced if the worker is female. Estimated effects are consistent with the
      hypothesis that the predominant impact of outreach is to crystallize existing
      latent demand for contraception. Results also suggest, however, that female
      worker outreach generates new demand by fostering ideational change.

PMID- 8153965
TI  - Gender ideology and fertility strategies in an Ekiti Yoruba village.
AB  - This article investigates the influence of gender ideology on number of children
      wanted, son preference, family-size discussions and decision-making, and use of
      birth control in a rural Ekiti Yoruba village in southwestern Nigeria. Interview
      and survey data indicate that attitudes about these matters vary more with age
      than with sex, suggesting that both women and men subscribe to the prevailing
      gender ideology of male authority in matters of family size and composition.
      However, women and men differ about who decides family size, largely because the
      ideal of fathers' financial support of their children is sometimes belied by
      practice. The article concludes with a discussion of the strategies that husbands
      and wives employ to obtain their reproductive goals, and their implications for
      family planning programs in Nigeria.

PMID- 8153966
TI  - Culture, maternal health care, and women's status: a comparison of Morocco and
      Tunisia.
AB  - This report assesses the role of demographic, socioeconomic, and cultural factors
      in explaining differentials in maternal health-care use in North Africa. Analyses
      of the Demographic and Health Surveys for Morocco and Tunisia show substantial
      differences in the use of prenatal care and in the proportion of home compared
      with hospital births, both within and between the two countries. The findings
      raise the question of whether lower use rates are a reflection of the low status
      of women. The question is addressed first through a statistical analysis of the
      differences within the two countries in terms of the demographic, socioeconomic,
      and educational characteristics of individuals, and second, through a comparison
      of the social context, health-care systems, and population policies of the two
      countries. The findings are interpreted in light of field research on the
      cultural context of maternal health care.

PMID- 8153967
TI  - Constrains on effective family planning in urban Sudan.
AB  - This article is an investigation of the constraints on contraceptive use in
      Sudan, from the perspective of current nonusers, never-users, and discontinuers,
      based on data obtained from 305 married women aged 15-49 through a field survey
      undertaken in Khartoum city. Results indicate that lack of knowledge of
      contraceptive methods accounts for the low level of contraceptive prevalence, 15
      percent overall, found in this study. The overwhelming majority of nonusers (85
      percent) either perceive contraception as a risk to their health and fertility,
      regard it as unacceptable, or do not know which method to choose. A comprehensive
      and rigorous family planning information program is crucial to address existing
      constraints on the use of contraceptives in urban Sudan.

PMID- 8153968
TI  - The need for quasi-experimental methodology to evaluate pricing effects.
AB  - Family planning program managers may be easily misled by conclusions about the
      effects of price increases on the demand for services when the findings are based
      on pre-experiments such as the single-group pretest-posttest study, generally
      believed to be practical. This report presents financial and service data from
      clinics of the Asociacion Pro-Bienestar de la Familia Ecuatoriana (APROFE) in
      Ecuador, which, analyzed according to the single-group pretest-posttest design,
      would suggest that the demand for intrauterine device services is inelastic.
      However, considerable demand elasticity is detected when data are analyzed
      according to more rigorous quasi-experimental designs. Using the single-group
      pretest-posttest design for pricing studies is too flawed to be considered
      practical. Wherever possible, strong designs should be used in operations
      research, especially in pricing studies.

PMID- 8153969
TI  - Namibia 1992: results from the Demographic and Health Survey.

PMID- 8153970
TI  - [The Paracelsus dramas of Martha Sills-Fuchs in the circumstances of Julius
      Streicher's Society of German Public Health].
AB  - Between 1936 and 1939 the Hungaro-Austrian author Martha Sills-Fuchs (1896-?)
      wrote three plays, in which Theophrast von Hohenheim, called Paracelsus is the
      main figure. Written for the ideological purposes of the 'Verein Deutsche
      Volksheilkunde', founded in 1935 by the radical German Nazi-leader Julius
      Streicher, Paracelsus was--totally neglecting the historical facts--shown as a
      precursor of Nazism. It could be demonstrated by detailed analysis, that Martha
      Sills-Fuchs sketched Paracelsus as a racist, a fighter against the jews, a
      follower of a mystical 'blood and soil'-ideology and as a medical doctor, who had
      great respect of 'mother nature' (as the Nazis claimed they had).

PMID- 8153971
TI  - [The therapeutics of Paracelsus with reference to natural philosophy, alchemy and
      psychology].
AB  - The controversial reception of Paracelsus is still going on. The crucial question
      is whether he is a man of the Middle Ages or of modern times. It is not possible
      to give a simple answer. We have to study the writings of Paracelsus within the
      scientific and cultural context of the Renaissance. This period is characterized
      by a new concept of natural philosophy. The theory of signature tries to read or
      translate certain constellations within the natural environment as a secret code.
      The idea of a sympathetic correspondence between natural bodies or substances
      implies the possibility of magical healing. A wellknown example is the
      preparation of the 'weapon salve'. There are two realities of spiritual powers at
      the same time: demons from the outside of the human body and powers of the mind
      from its inside which influence the body functions. The natural philosophy of the
      Renaissance tries to 'naturalize' the demons as a complement of matter.
      Paracelsus reflects the ideas of his time. The human being has got two bodies: a
      visible one which belongs to earth and an invisible one which belongs to heaven.
      The 'philosopher' as a pharmacist and a doctor has to detect the invisible body
      corresponding with the celestial world (stars, planets) by analysing the manifest
      astrological signs. The alchemical preparation of remedies has to purify the
      specific healing substances ('arcana') from the crude material. The pharmacist
      and doctor just imitates artificially the quasi alchemical metabolic process of
      nature itself continuing and finishing it. Paracelsus' concept of imagination
      ('imaginatio') implies a psychosomatic model how far spiritual powers can
      influence the body functions. Paracelsus stresses radically the importance of
      suggestions as a source of illness. The synchronical concepts are confusing
      today. Knowledge and superstition, scientific rationality and irrational
      speculations come together and can hardly be separated. Nevertheless, at the end
      of the 20th century we may have more mental relations to this scenario than we
      are able to realize it at the moment.

PMID- 8153972
TI  - [Medical magic of Paracelsus and Paracelsus followers: weapon salve].
AB  - The doctrine of 'transplantatio morborum' may be considered a branch of the
      'magia naturalis'-philosophy which was widespread in the sixteenth century.
      According to this doctrine, ailments and remedies can be transferred from one
      body to another. A further example of this field of medicine is gun salve, which
      we find mentioned particularly in the works of the Paracelsists of the
      seventeenth and eighteenth centuries. Even though salve of various types had
      already been used for some time in the treatment of stab wounds, gun salve was
      imputed to have magnetic properties which gave rise to 'actio in distans',
      whereby the smearing of gun salve onto the weapon caused the wound to be healed.
      An early example of a description of its formula can be found in the first book
      of the 'Archidoxis magica': one of the works which have been wrongly attributed
      to Paracelsus. Early in the seventeenth century, this formula for gun salve-
      frequently with modifications--found its way into the writings of the followers
      of Paracelsian doctrine: of Oswald Croll, for example, or Rudolph Goclenius. When
      the concept of 'actio in distans' was propounded, an argument soon developed as
      to whether gun salve should be classified under 'magia naturalis' or 'magia
      daemoniaca'. Determined opposition to Goclenius was proferred in the person of
      Jean Roberti, a Belgian Jesuit who accused the Protestant Goclenius of consorting
      with demons. A number of treatises appeared in close succession, with Johann
      Baptist van Helmont emerging as the mediator in the argument. Yet he too came
      under attack at the hand of the Jesuit Roberti, with the result that, at least by
      the time Athanasius Kircher had also become embroiled in the debate, the dispute
      was pursued principally between orthodox Trentino Catholicism and heterodox
      Protestantism. An analysis of the writings on the subject of gun salve
      demonstrates how easily a discussion which was originally of a purely medical,
      scientific nature could lead to a religious controversy in that denominational
      age.

PMID- 8153973
TI  - [The lay theology of Paracelsus from the traditional historical viewpoint and its
      classification to Reformation and Catholic reform].
AB  - Certain aspects of the theological oeuvre of Paracelsus--a body of work first
      described in painstaking detail and on the basis of the sources by Kurt Goldammer
      -still resist our understanding of them in appropriate historical terms. This
      circumstance is apparent in the various unanswered questions posed by the very
      biography of the physician and theologian: was his critical, reform-minded
      position vis-a-vis the Church in any way relevant to his choice of Strasbourg as
      a place of residence or to his being called to the position in Basel? Can certain
      manifestations in the activities of Paracelsus, who died within the Roman
      Catholic Church, be viewed as signs of a Nicodemism such as characterizes Agrippa
      von Nettesheim (a figure in some ways so close to Paracelsus)? From the very
      start, Hohenheim's accounts of himself reveal the art of medicine and theology as
      inextricably linked to one another. And in its development this linkage becomes
      in turn an essential element of autobiographical interpretation, with the result
      that the healing art, Christian faith, and the living of life are fused, through
      the self-awareness and activity of Paracelsus, into a fascinating unity. From
      this perspective, it proves to be difficult to assign his theological, world',
      having as it does its place in his total view of things, one based on Renaissance
      philosophy, to any single tendency or direction within the spectrum of
      Reformation thought and its critical approaches to the church establishment.
      Admittedly, in particular areas we may well suppose such a dependence to have
      existed, and certain classifications remain a possibility. But an affiliation of
      this kind, despite partial parallels in, say, the thought of Schwenckfeld, seems
      to break down precisely in the case of Paracelsus's teaching on the Eucharist;
      for at the heart of his Eucharistic ideas stands a distinctive concept of,
      limbus'--very likely unmatched in the thought of the Spiritualists--which is
      shaped by a distinction between what is earthly or mortal and what is heavenly,
      immortal. The same difficulty persists as well with the Paracelsian notion of the
      Christian magus. Here there are definitely models to be found in Renaissance
      philosophy; the magus concept peculiar to Paracelsus, however, is especially
      evocative of the unity (v.s.) characteristic of this physician-theologian in
      particular.

PMID- 8153974
TI  - [Paracelsus research past and present: basic results, frustrated attempts, new
      approaches].
AB  - As is well known, the Leipzig historian of medicine Karl Sudhoff inaugurated
      modern research on Paracelsus, providing it with a basis that has remained
      indispensable right down to the present. Pertinent scholarly contributions by
      Sudhoff date from 1887; they culminated first in the Paracelsus bibliography of
      1894 and reached their fitting conclusion with the edition of Hohenheim's
      collected works, Abteilung 1: Medizinische, naturwissenschaftliche und
      philosophische Schriften; its fourteen volumes appeared between 1922 and 1933.
      Following the second world war the Marburg historian of religion Kurt Goldammer
      undertook the edition of Abteilung 2: Theologische und religionsphilosophische
      Schriften; this edition, building on Sudhoff's work, is likewise conceived as
      comprising fourteen volumes, of which six (together with a supplement), that is,
      half the projected total, have appeared so far (through 1986). Alongside these
      fundamental achievements, however, Paracelsus research in the more recent past
      has also been marked by a series of failed attempts. One of these is the index
      volume to the Sudhoff edition; it was put together under difficult circumstances,
      and even at the time of its appearance (1960) it failed to fully satisfy
      scholarly criteria. A further unsatisfactory aspect, it may be recalled, is the
      Paracelsus lexicon which was begun forty years ago, but which, despite the
      pressing need for a research tool of this kind, has still not appeared. Finally,
      it has not been possible, despite repeated efforts, to establish a Paracelsus
      institute in the sense of a centre for historical research. Under these
      circumstances, the continued care for what Paracelsus has bequeathed to us and
      the coordination of related activities have down to the present been provided for
      solely by the two pertinent professional societies, the Schweizerische Paracelsus
      Gesellschaft (founded in 1942) and the Internationale Paracelsus-Gesellschaft
      (created in 1951), along with their respective periodical publications. A renewal
      in Paracelsus research today should accordingly not be limited to the
      investigation of discrete problems, still unresolved, that bear on Hohenheim and
      his work; indeed, new efforts should focus above all on clearing up, through
      interdisciplinary cooperation, the above-mentioned desiderata.

PMID- 8153975
TI  - [Valentin Rosswurm: on the social history of Paracelsism in the 16th century].
AB  - The reactions awakened in his own day by the lithotomist Valentin Rosswurm were
      not many but varied. Up to now only the controversy about his Paracelsus
      connection has been mentioned in some studies on Paracelsian medicine in 16th
      century England. Nothing has been known so far about the social background of the
      foreign doctor who came to England from the Continent. New documents found in
      various European archives enable us to reconstruct the career of another disciple
      of Paracelsus who earned his living by lithotomy and herniotomy, being one of the
      many itinerant surgeons who flocked European cities in the early modern period.
      The new evidence also does justice to a man accused of being a quack by his
      English critics but who was in fact an experienced and literate surgeon no better
      and no worse than the local healers with whom he competed for wealthy clients.

PMID- 8153976
TI  - [Functional status of the elderly measured with the Sickness Impact Profile].
AB  - The Sickness Impact Profile (SIP) is a generic questionnaire developed to
      register the consequences of disease for daily life. We examined an open
      population (N = 232) aged 65 years and older irrespective of their health status
      by means of the SIP in order to obtain age related reference values. In addition
      to patient characteristics data on the patient's morbidity and health appraisal
      were collected. There appeared to be no relation between SIP-scores and sex. Age,
      however, as well as morbidity and health appraisal were significantly related to
      SIP-scores. These results emphasize the importance of the availability of age
      related reference values in outcome studies.

PMID- 8153977
TI  - [Behavior profile of psychogeriatric patients in substitute care projects:
      nursing home care and home for the aged].
AB  - This article describes behaviour profiles of psychogeriatric patients
      participating in some substitute care projects. The behaviour of 55 patients from
      five residential homes participating in these projects were rated on the
      Behaviour Rating Scale for Psychogeriatric Inpatients (GIP). These data were
      compared with GIP-data of two reference groups: elderly people in residential
      homes and patients in psychogeriatric nursing homes (supervision, intensive care
      and nursing care requiring patients). Patients in the projects have, compared to
      the other people in residential homes, more cognitive and social disabilities.
      Compared to the patients in nursing homes, the patients in the projects have less
      social, cognitive and psychomotor disabilities, but more emotional problems, like
      suspicious, melancholic and dependent behaviour. These results show that patients
      in substitute care projects have a specific behaviour profile. The profile can be
      used for careful selection of patients in these projects.

PMID- 8153978
TI  - [Implicit memory in patients with Alzheimer disease: a concise review].
AB  - Experimental psychologists have made a distinction between explicit and implicit
      memory tasks. In contrast to explicit tasks implicit ones do not refer to
      conscious recollection of a previous learning episode. Implicit memory is
      revealed by a change in task performance which can be attributed to previous
      learning. Amnesic patients, by definition, perform poorly on explicit memory
      tasks, but exhibit normal performance on certain implicit tasks. In recent years,
      investigators have studied the implicit memory capabilities of patients with
      Alzheimer's disease. The present article aims to give an overview of the
      performance of Alzheimer patients on four tasks of implicit memory. Compared with
      normal elderly persons, patients with Alzheimer's disease seem to demonstrate
      impaired performance on conceptual, but not on perceptual implicit memory tasks.
      This dissociation could yield important information about the neurological
      systems subserving implicit memory processes. Some suggestions for future
      research into implicit memory in Alzheimer patients are given.

PMID- 8153979
TI  - [Charity. Poor welfare as care for the elderly in the 2nd half of the 19th
      century].
AB  - In the second half of the nineteenth century poor relief of the church was
      especially directed at the elderly. Firstly, this is clear from the existence of
      almshouses and the so-called old people's homes. Secondly, in allocating poor
      relief age played an important role. Permanent outdoor relief was supplied from
      the age of fifty. This article will portray this nineteenth century permanent
      outdoor relief. A group of 239 permanently endowed people will be analyzed on the
      basis of parish registers of the Evangelical-Lutheran church in Amsterdam. This
      specific group (orphanages, almshouses, old people's homes and boarders will not
      be considered) consisted largely of elderly people.

PMID- 8153980
TI  - [Low serum vitamin B 12 level and vitamin B 12 deficiency in the elderly. When
      should supplement be provided?].
AB  - Low serum vitamin B12 levels and vitamin B12 deficiencies are frequently found in
      the elderly. The full syndrome of a vitamin B12 deficiency is rather simple to
      diagnose. The large applicability of the vitamin B12 assay also gives rise to
      many probably incomplete features. Low/low-normal vitamin B12 levels in screening
      procedures raise uncertainty whether this finding represents deficiency and
      should be followed by supplementation. In this paper the occurrence of low serum
      levels of vitamin B12 are discussed. To assess the clinical relevance of low/low
      normal outcomes supplementary diagnostic procedures will be needed. Within this
      scope we illustrate the d.o.s.-test and the MMA-assay. Especially the latter will
      probably provide more answers to the treatment question. Systematic research is
      needed to clarify this issue. Meanwhile supplementation of all low and low-normal
      outcomes of the B12-assay seems the best answer.

PMID- 8153981
TI  - [Antipsychotic agents in patients with dementia].

PMID- 8153982
TI  - Micronutrients and tropical infections.
AB  - There is now considerable evidence for bidirectional interactions between
      micronutrients and tropical infections but it is clear that research to date has
      only touched the surface of the problem and much remains to be learned at both
      the basic science and public health levels. Much research has been directed
      towards iron and there is increasing interest in zinc and vitamin A, but other
      micronutrients have been largely ignored. The few available studies on
      antioxidants suggest that these nutrients may also have important effects on
      tropical infections and further research is warranted. In addition, there is a
      need for information on appropriate methods of assessing status of particular
      micronutrients during infection, which is often endemic in populations likely to
      be deficient, in order to improve interpretation of research results and provide
      a more secure basis for any clinical or public health supplementation programmes.

PMID- 8153983
TI  - Comparison of the sensitivity of different geographical races of Onchocerca
      volvulus microfilariae to ivermectin: studies in vitro.
AB  - This study was designed to provide baseline information on the sensitivity of 4
      geographical isolates of Onchocerca volvulus microfilariae (mf) (Ghana forest,
      Ghana savanna, Cameroon forest and Guatemala) to ivermectin, and to develop an in
      vitro system with which to examine parasites for the possible development of drug
      resistance. Drug effects were best visualized in the presence of monkey kidney
      (LLCMK2) feeder cells in the culture system (MEM medium+20% serum), since mf
      maintained in the absence of cells declined in condition rapidly. Incubation of
      Ghana forest mf (+cells) in ivermectin (10(-5)-10(-10) M) caused a decrease in
      motility index (MI) scores in a concentration-dependent fashion; drug effects
      could be observed as early as 6 h, but cultures maintained for up to 8 d showed
      greater differences between control and drug groups with increasing time. All 4
      O. volvulus isolates and O. lienalis (bovine) were compared for their response to
      ivermectin (10(-7) M): O. lienalis mf were significantly more sensitive (78%)
      reduction in MI scores on day 8) than the O. volvulus isolates (33.4-47.7%
      reduction). O. volvulus microfilariae ex utero generally displayed lower levels
      of motility and were slightly less inhibited by ivermectin than were skin mf. The
      in vitro system described can distinguish between the populations of mf studied
      on the basis of differing MI responses to ivermectin and, when combined with
      assays to test the infectivity of mf to blackflies following exposure to drug,
      will provide methods with which to examine parasites for the possible development
      of resistance.

PMID- 8153984
TI  - Ivermectin 400 micrograms/kg: long-term suppression of microfilariae in
      Bancroftian filariasis.
AB  - Forty-three Wuchereria bancrofti carriers were given 4 successive semi-annual
      single doses of ivermectin 100 micrograms/kg (IVER 100). The geometric mean
      microfilaremia (mf) recurrence percentages, compared to the pre-initial treatment
      mf level, were 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 15 individuals, considered as 'bad responders'. At month 24, the subjects were
      randomly allocated into 2 groups: the first group was treated with a fifth dose
      of IVER 100 and the second with a first, single dose of 400 micrograms/kg of
      ivermectin (IVER 400). At month 30, the mf recurrence percentage was
      significantly higher in patients treated with IVER 100 than in those receiving
      IVER 400 (61% vs. 8%, P < 0.05). In the IVER 100 group, 6 of the 8 'bad
      responders' remained 'bad responders', whereas only 2 of 7 did so in the IVER 400
      group. Only 3 additional patients in the IVER 100 group became consistently
      amicrofilaraemic, whereas 9 did so in the IVER 400 group. Two 'good responders'
      in the IVER 100 group became 'bad responders'. A single dose of 400 micrograms/kg
      of ivermectin has been demonstrated to be efficient for the treatment of carriers
      refractory to repeated doses of 100 micrograms/kg and to result in better long
      term mf suppression. These results suggest a possible effect of 400 micrograms/kg
      of ivermectin on macrofilaria.

PMID- 8153985
TI  - Albendazole and infections with Ascaris lumbricoides and Trichuris trichiura in
      children in Bangladesh.
AB  - Two hundred and forty-five children infected with Trichuris trichiura, 143 of
      whom were also infected with Ascaris lumbricoides, were treated with albendazole
      as follows: single doses of either 600 mg or 800 mg, or daily doses of 400 mg for
      either 3 d or 5 d. Three stools were examined over a period of 10 d after
      treatment and again after nearly 40 d, using a quantitative microscopical
      technique. Albendazole appeared to act slowly against A. lumbricoides but within
      10 d all dosages had cured about 92% of infections. In contrast, albendazole
      appeared initially to inhibit egg production by T. trichiura, which was then
      resumed. The single doses gave poor cure and egg reduction rates for T. trichiura
      of less than 30% each, and 400 mg of albendazole for 3 d was required to achieve
      a cure rate of 80%. The implications of these results are briefly discussed.

PMID- 8153986
TI  - Differentiation of Naegleria fowleri from other species of Naegleria using
      monoclonal antibodies and the polymerase chain reaction.

PMID- 8153987
TI  - Malaria transmission-blocking activity in experimental infections of Anopheles
      gambiae from naturally infected Plasmodium falciparum gametocyte carriers.
AB  - Experimental infections of anopheline mosquitoes were carried out with Plasmodium
      falciparum gametocytes from 65 naturally infected patients in Cameroon. A
      comparison was made between infections with blood containing autologous plasma
      and blood in which the plasma was replaced with plasma from a donor without
      previous malaria exposure. A lower infection rate was observed in 50 of 65
      autologous plasma samples. Transmission was significantly blocked in 3
      infections. This indicates that, in a population living in an area endemic for
      malaria, blood plasma factor(s) can reduce the transmission capacity of
      gametocyte carriers to mosquitoes.

PMID- 8153988
TI  - Laboratory transmission of Venezuelan equine encephalomyelitis virus by the tick
      Hyalomma truncatum.

PMID- 8153989
TI  - Chagas disease in north-west Argentina: risk of domestic reinfestation by
      Triatoma infestans after a single community-wide application of deltamethrin.
AB  - The risk of domestic reinfestation by Triatoma infestans after a single community
      wide application of delta-methrin (2.5% suspension concentrate at 25 mg active
      ingredient/m2) was studied in Amama, north-west Argentina, where no insecticide
      spraying had been done by official control services. The percentage of infested
      houses fell from 88% before spraying in 1985 to nil during the 6 months after
      spraying, and thereafter increased from 5% in 1986 to 96% before a second
      treatment in 1992, fitting closely to a logistic model (r2 = 0.997). Significant
      risk factors associated with domestic reinfestation determined from stepwise
      logistic regression and one-factor analysis were the density of T. infestans in
      bedrooms just before spraying and the surface structure of indoor walls. Peak
      densities of bugs in 1988-1989 significantly differed between levels of both risk
      factors. Our study suggests the existence of stable determinants of infestation
      linked to the household which, in the absence of effective control measures,
      would also determine the speed of house recolonization and the ensuing bug
      densities. Plastering of mud walls before application of insecticides to all
      domestic and peridomestic structures is supported by the study.

PMID- 8153990
TI  - Diagnosis of Plasmodium falciparum infections in mummies using the rapid manual
      ParaSight-F test.

PMID- 8153991
TI  - Human visceral leishmaniasis in Alpes-Maritimes, France: epidemiological
      characteristics for the period 1985-1992.
AB  - In 8 years (1985-1992), 65 cases of human visceral leishmaniasis (HVL) have been
      diagnosed in the department of Alpes-Maritimes, France, 56 of them having been
      infected locally. The annual frequency has increased from 3 cases in 1985 to 15
      cases in 1992. There is a low rate of paediatric cases (29%) and a predominance
      of males among adult cases (85%). Since 1986, 19 cases of co-infection with
      Leishmania and human immunodeficiency virus 1 have been reported, corresponding
      to 40% of adult cases and to 30% of the total cases. The frequency of co
      infections is stable at about 3 per annum. Isoenzymatic identification of the
      strains isolated from patients confirmed Leishmania infantum zymodeme MON-1 as
      responsible for most if not all HVL in the department of Alpes-Maritimes; 42 of
      the 44 strains isolated belonged to that zymodeme.

PMID- 8153992
TI  - A zoonotic focus of cutaneous leishmaniasis due to Leishmania tropica at Utut,
      Rift Valley Province, Kenya.
AB  - Several foci of cutaneous leishmaniasis have been identified in central Kenya and
      the Rift Valley. One of these was the Utut focus of Leishmania tropica on the
      floor of the Rift Valley between Gilgil and Elementaita, where intense
      transmission was detected. High infection and scar rates were detected among
      illegal charcoal burners in a previously uninhabited forest reserve on a lava
      flow containing numerous caves and rock crevices inhabited by sandflies and
      mammals which included hyraxes. Multiple lesions, predominantly in the head
      region, were common. 33% of cases occurred in people who had been less than one
      year in the area. Although most lesions healed within one or 2 years, some large,
      recrudescing lesions lasted several years.

PMID- 8153993
TI  - First report of visceral leishmaniasis in Nicaragua.

PMID- 8153994
TI  - Meriones libycus (Rodentia: Gerbillidae), a possible reservoir host of zoonotic
      cutaneous leishmaniasis in Riyadh province, Saudi Arabia.

PMID- 8153995
TI  - Evolution: the art of survival.

PMID- 8153996
TI  - Phlebotomus papatasi (Scopoli), vector of zoonotic cutaneous leishmaniasis in
      Riyadh province, Saudi Arabia.

PMID- 8153997
TI  - Efficient assessment of filariasis endemicity by screening for filarial
      antigenaemia in a sentinel population.
AB  - We have previously reported that a monoclonal antibody-based antigen detection
      assay (AD12) is sensitive and specific for Bancroftian filariasis in Egypt. The
      purpose of the present study was to demonstrate the use of this assay in a
      sentinel population as a means of efficiently screening for filariasis
      endemicity. Antigen testing was performed with finger-prick blood collected
      during the day from 743 schoolchildren (ages 11-16 years). The school draws
      students from 5 villages in Qalubia Governorate, 35 km north-east of Cairo,
      Egypt. The prevalence of filarial antigenaemia in the school was 17.2%.
      Antigenaemia rates in children from the 5 villages were 29, 20, 18, 17, and 10%
      (non-uniformity significant by chi 2 analysis, P = 0.02). These data agree with
      Ministry of Health rankings of relative endemicity for these villages based on
      prior night blood surveys. The village with the highest antigen prevalence in
      children was surveyed one year before the present study. Prevalence rates of
      antigenaemia and microfilaraemia at that time for a different sample of children
      aged 11-16 years were 33% and 22%, respectively. We conclude that antigen
      detection in schoolchildren of this age group is an efficient means of assessing
      filariasis endemicity in Egypt.

PMID- 8153998
TI  - Low rate of reinfection with Enterobius vermicularis in a Papua New Guinea
      village.

PMID- 8153999
TI  - Aggregation and predisposition to Ascaris lumbricoides and Trichuris trichiura at
      the familial level.
AB  - This study examines the persistence of familial aggregation and familial
      predisposition to Ascaris lumbricoides and Trichuris trichiura infection over 2
      periods of treatment and reinfection, in an urban community in Kuala Lumpur,
      Malaysia. Both parasite species were shown to be aggregated (assessed by the
      variance to mean ratio) within families at all 3 interventions, although no
      consistent trend in aggregation was observed over the period of the study.
      Associations between mean A. lumbricoides and T. trichiura infection levels of
      families, at all 3 interventions, were highly significant (P < 0.0001),
      suggesting persistent predisposition at the family level.

PMID- 8154000
TI  - Epidemiological investigation of Taenia solium taeniasis and cysticercosis in a
      rural village of Michoacan state, Mexico.
AB  - We performed a survey for taeniasis and cysticercosis among persons living in a
      Mexican village where Taenia solium infection in pigs was known to be enzootic. A
      standardized questionnaire was administered in all 577 households to obtain
      medical histories and information on demographic and environmental factors and on
      risk factors associated with transmission of infection. Serum and/or stool
      specimens were obtained from 1005 volunteers and examined for cysticercosis
      antibodies and intestinal parasites. Faecal examination of 828 participants
      revealed infection by Taenia sp. in 2 (0.2%). Three additional cases of taeniasis
      were detected in individuals who evacuated proglottids after treatment with
      praziquantel. Of 1005 human serum specimens, 49 (4.9%) were positive in the
      cysticercosis immunoblot assay. Seropositivity increased with age and reached a
      peak in subjects aged 46-55 years (P < 0.05). A history of seizures was
      significantly associated with seropositivity (P < 0.05); approximately 25% of
      persons with such histories were seropositive. Histories of headache, dizziness,
      trembling, blurred vision, and vomiting were also significantly associated with
      positive immunoblot assays. This study has demonstrated previously undiagnosed
      morbidity associated with T. solium neurocysticercosis and identified community
      behavioural and environmental practices that must be modified to prevent
      continued transmission of cysticercosis and taeniasis.

PMID- 8154001
TI  - High prevalence of anti-hepatitis C virus antibodies in a Cameroon rural forest
      area.
AB  - Sera of 807 people living in a rural forest area in southern Cameroon were tested
      by enzyme-linked immunosorbent assay; 101 (12.5%) gave positive results and were
      confirmed by line immunoassay. There was a highly significant difference between
      subjects aged over 40 years and those under 40 years, with the former having a
      much higher prevalence of antibodies. There were also significant differences
      between antibody prevalences among subjects aged > 40 years in the 3 ethnic
      groups studied--Baka Pygmies (6%), Fangs (30%) and Boulous (44%). Further studies
      are necessary to determine the reasons for these differences.

PMID- 8154002
TI  - Low risk of sexual transmission of hepatitis C virus in Somalia.
AB  - The prevalence in Somalia of antibody to hepatitis C virus (anti-HCV) was
      determined in a survey of 236 female prostitutes, 80 sexually transmitted disease
      (STD) clinic patients, 79 male soldiers, and 43 tuberculosis patients. Of 98
      (22%) serum samples repeatedly anti-HCV reactive by first and second generation
      enzyme-linked immunosorbent assay kits, only 8 (1.8%) were anti-HCV positive by
      immunoblot assay (RIBA-2). Anti-HCV seropositivity by immunoblot assay was not
      associated with any risk group or with positive syphilis serology (found in 18%
      of subjects) or antibody to human immunodeficiency virus 1 (in 1.4% of subjects).
      These data indicate that sexual transmission of hepatitis C virus is not common
      in Somalia among sexually active populations, including female prostitutes and
      other groups at high risk of STDs and the acquired immune deficiency syndrome.

PMID- 8154003
TI  - Hepatitis E virus in Indonesia.

PMID- 8154004
TI  - The basic reproduction number for dengue fever in Sao Paulo state, Brazil: 1990
      1991 epidemic.

PMID- 8154005
TI  - Reduced efficacy of chemotherapy might accumulate concurrent HTLV-1 infection
      among strongyloidiasis patients in Okinawa, Japan.

PMID- 8154006
TI  - The seroprevalence of syphilis, toxoplasmosis and hepatitis B in patients in
      Bahrain infected with human immunodeficiency virus.

PMID- 8154007
TI  - QBC: rapid filaria diagnoses from blood--Mansonella ozzardi and Wuchereria
      bancrofti.

PMID- 8154008
TI  - Lactic acidosis and hypoglycaemia in children with severe malaria:
      pathophysiological and prognostic significance.
AB  - Serial clinical and metabolic changes were monitored in 115 Gambian children (1.5
      12 years old) with severe malaria. Fifty-three children (46%) had cerebral
      malaria (coma score < or = 2) and 21 (18%) died. Admission geometric mean venous
      blood lactate concentrations were almost twice as high in fatal cases as in
      survivors (7.1 mmol/L vs. 3.6 mmol/L; P < 0.001) and were correlated with levels
      of tumour necrosis factor (r = 0.42, n = 79; P < 0.0001) and interleukin 1-alpha
      (r = 0.6, n = 34; P < 0.0001). Admission blood venous glucose concentrations were
      lower in fatal cases than survivors (3.2 mmol/L, vs. 5.8 mmol/L; P < 0.0001).
      Treatment with quinine was associated with significantly more episodes of post
      admission hypoglycaemia when compared with artemether or chloroquine. After
      treatment, lactate concentrations fell rapidly in survivors but fell only
      slightly, or rose, in fatal cases. Plasma cytokine levels fluctuated widely after
      admission. Sustained hyperlactataemia (raised lactate concentrations, 4 h after
      admission) proved to be the best overall prognostic indicator of outcome in this
      series. Lactic acidosis is an important cause of death in severe malaria.

PMID- 8154009
TI  - Parasite density of Plasmodium falciparum malaria in Ghanaian schoolchildren:
      evidence for influence of sex hormones?

PMID- 8154010
TI  - Serum neopterin in patients with Chagas disease.

PMID- 8154011
TI  - Acute Manson's schistosomiasis: sonographic features.

PMID- 8154012
TI  - Abdominal wall mycetoma: an unusual presentation.

PMID- 8154014
TI  - Clinical isolates of HIV-associated cryptococcosis in Nairobi, Kenya.

PMID- 8154013
TI  - Snake bite and antivenom complications in Belo Horizonte, Brazil.
AB  - Factors associated with clinical complications of snake bite and antivenom
      therapy were studied in 310 hospital patients admitted with snake bite over 6
      years to a tertiary referral hospital in Belo Horizonte, southeast Brazil.
      Overall, 17.4% had early clinical complications including tissue loss associated
      with abscess and necrosis, acute renal failure, shock, acute lung oedema and
      intracranial haemorrhage. 3% had permanent sequelae, caused by muscle
      contractures and amputations, chronic renal failure, or death. Early
      complications were associated with the following: age under 9 years (P = 0.04),
      residence in a rural area (P = 0.04), and a delay of more than 8 h in seeking
      clinical care (P < 0.01). Antivenom was administered to 98.1% of patients; 13.8%
      presented with anaphylaxis and 11.8% with pyrexia. Individuals from a rural area
      had a higher occurrence of anaphylactic reactions (P = 0.03). Neither anaphylaxis
      nor pyrexia was linked with antivenom type and dosage. This study suggested that
      antivenom might be associated with a reduced risk of serious injuries related to
      snake bite, especially when administered within the first 8 h. Complications
      appeared to be a far greater risk than adverse reactions to the antivenom.

PMID- 8154015
TI  - Traveller's diarrhoea; a controlled study of its effect on chloroquine and
      proguanil absorption.
AB  - The potential for traveller's diarrhoea to impair proguanil and chloroquine
      absorption and cause chemoprophylaxis failure was investigated in a study
      involving recently returned travellers who were either asymptomatic or presented
      with diarrhoea. A routine dose of chemoprophylaxis was administered to 12
      travellers with diarrhoea and 12 asymptomatic subjects. The subjects undertook a
      lactulose-mannitol intestinal permeability test and were bled hourly after
      prophylaxis ingestion. Plasma analysis of chloroquine and proguanil from serial
      samples revealed a significantly lower proguanil Cmax (146 ng/mL vs. 196 ng/mL, P
      = 0.05), and longer tmax (3.1 h vs. 2.6 h, P = 0.05) in the diarrhoea cohorts.
      The absorption coefficient was lower for proguanil (0.57 vs. 0.76) but the
      difference did not quite reach levels of significance. Chloroquine kinetics were
      similar in both groups. The diarrhoea cohort had a three-fold higher lactulose
      absorption, influencing the mean lactulose mannitol:ratio, 0.114 +/- 0.17
      compared to the control ratio of 0.02 +/- 0.01 (P = 0.04). Symptomatic subjects
      had impaired mucosal function which reduced the absorption of proguanil but not
      chloroquine, a phenomenon which may reduce prophylactic efficacy.

PMID- 8154017
TI  - Intravascular haemolysis following halofantrine intake.

PMID- 8154016
TI  - Parenteral therapy of moderately severe malaria: comparison of intramuscular
      artemether and intramuscular sulfadoxine-pyrimethamine.
AB  - We have compared the efficacy of intramuscular artemether against intramuscular
      sulfadoxine-pyrimethamine in an open randomized study in children with severe but
      uncomplicated malaria. Parasite clearance time and fever clearance time were
      faster with artemether. The parasitological clearance on day 14 was 100% for
      artemether and 98% for sulfadoxine-pyrimethamine, but 8 patients in the
      artemether group and 1 in the other group had a recrudescence of parasitaemia.
      There was no toxic reaction of note in either group. We therefore suggest that
      artemether is a good alternative to the currently used drugs in the parenteral
      treatment of severe but uncomplicated malaria and may be useful in preventing the
      possible development of cerebral malaria.

PMID- 8154018
TI  - Topical treatment of American cutaneous leishmaniasis with paramomycin and
      methylbenzethonium chloride: a clinical study under field conditions in Ecuador.
AB  - Fifty-two patients with American cutaneous leishmaniasis (ACL) from the Pacific
      coast of Ecuador were treated topically with an ointment containing 15%
      paramomycin (PR) and 12% methylbenzethonium chloride (MBCL) in vaselinum album
      (white soft paraffin; white petrolatum). After 20 applications (over 10 or 20 d)
      all lesions showed complete epithelialization within the first 100 d. Five
      patients developed new lesions during the one year observation period; 2 of these
      were probably reinfections. Considering all 5 cases as treatment failures, the
      healing rates were: 72% after 50 d, 90% after 100 d, and 85% after 360 d. In a
      separate study in the same area, a group of 23 patients was left without
      treatment for 3 months. Only 9% of the untreated patients healed spontaneously
      after 50 d. Growth of the lesion, inflammation and pain were observed at the
      beginning of treatment. After treatment, most lesions healed rapidly without
      scars. The drug was well accepted by the patients and was easy to administer
      under tropical field conditions.

PMID- 8154019
TI  - Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis
      following the combined administration of interferon-gamma and pentavalent
      antimonial compounds.
AB  - In an open trial, longer courses of pentavalent antimonials (Sbv) at sub-optimal
      doses (10 mg/kg body weight), in association with recombinant human interferon
      gamma (IFN-gamma) (100 micrograms/m2 of body surface area) were administered, by
      daily intramuscular injections, to 13 patients with diagnoses of cutaneous or
      mucocutaneous leishmaniasis unresponsive to Sbv. Four patients presented with
      large skin ulcers, and 9 had mucosal involvement as the main manifestation, the
      latter affecting the nose (3 cases), nose and septum (2 cases), nose and oral
      cavity (1 case), and nose, pharynx and larynx (3 cases). Except for one case with
      severe involvement of the upper respiratory tract, the lesions were fully
      resolved by the end of therapy (mean duration 40 +/- 12 [SD] d, range 30-60 d) in
      the 11 patients who completed therapy. The main side effects were headache and
      fever (7 cases), together with leucopenia and eosinophilia (4 cases). It is
      concluded that combined administration of low doses of Sbv plus IFN-gamma may
      provide a novel therapeutic approach for the treatment of antimony-resistant
      cutaneous or mucocutaneous leishmaniasis. The possible mechanisms by which IFN
      gamma contributes to resolution of the disease are discussed.

PMID- 8154020
TI  - Chemotherapy of Entamoeba histolytica: studies in vitro with bacitracin and its
      zinc salt.
AB  - Twenty-one Entamoeba histolytica isolates from a range of geographical locations
      and representing 3 different zymodemes were tested under xenic anaerobic
      conditions for their sensitivities to bacitracin and bactracin zinc. Isolates
      were over 13 times more sensitive to bacitracin zinc than to bacitracin. Our
      results indicate that bacitracin zinc may form the basis of an alternative non
      toxic treatment of luminal amoebiasis.

PMID- 8154021
TI  - Prolongation of in vivo mouse islet allograft survival by modulation of MHC class
      I antigen.
AB  - Major histocompatibility complex class I-deficient islets from beta-2
      microglobulin-deficient mice have been shown to have prolonged in vivo islet
      allograft survival. Additionally in vitro studies using the mixed lymphocyte
      islet coculture system have demonstrated a reduction in cytotoxic T lymphocyte
      activity against alloislets that have been pretreated with an antibody directed
      against MHC class I antigen. The clinical applicability of these findings are
      examined in this study, which evaluates the ability of MHC class I blocking
      antibody to prevent the in vivo destruction of alloislets. Recipients of
      allogenic islet transplants treated with phosphate-buffered saline or control
      F(ab')2 fragments rejected the transplanted alloislets in median times of 11.5
      days and 11 days, respectively. Recipient mice treated with a monoclonal antibody
      or F(ab')2 fragments specific to the donor MHC class I antigen had significant
      prolongation in allograft survival (median allograft survival for both groups was
      21 days) when compared with mice treated with PBS or control F(ab')2 fragment.
      These results demonstrate that treating recipients of alloislets with donor
      specific MHC class I monoclonal antibody or the respective F(ab')2 fragments
      prolongs islet allograft survival. This confirms the importance of MHC class I
      antigen in the rejection of pancreatic islet allografts and suggests that
      blocking different domains on the MHC class I molecule could be used
      therapeutically in the protection of allografts from the immune system.

PMID- 8154022
TI  - Retransplantation in miniature swine. Lack of a requirement for graft adaptation
      for maintenance of specific renal allograft tolerance.
AB  - In miniature swine, one-haplotype class I disparate renal allografts are accepted
      without exogenous immunosuppression by approximately 35% of recipients.
      Alternatively, transplants bearing a two-haplotype class I mismatch are always
      rejected acutely. However, long-term acceptance in the latter animals can be
      achieved uniformly with a 12-day course of cyclosporine. In vitro studies of
      recipient cell-mediated lymphocytotoxicity responses have shown donor-specific
      cytotoxic T lymphocyte clones in tolerant animals, suggesting that tolerance may
      be a local phenomenon or a central phenomenon activated in the milieu of the
      graft. Six animals were retransplanted with kidneys MHC-matched to their original
      allograft to determine whether (1) tolerance is a central phenomenon; (2) host
      tolerance can be broken with a fresh challenge of donor antigen and antigen
      presenting cells; and (3) graft adaptation is required for maintenance of
      tolerance. Four of the retransplanted animals had been spontaneous acceptors of
      one-haplotype class I-disparate grafts and two had been rendered tolerant to two
      haplotype class I-mismatched kidneys with CsA induction. All six explanted
      allografts showed no histological evidence of rejection and all six retransplants
      were accepted without exogenous immunosuppression. These findings suggest that in
      miniature swine tolerance of class I-disparate kidneys is a stable, centrally
      mediated phenomenon that cannot be broken with a challenge of fresh donor antigen
      and donor-type APCs. Furthermore, successful retransplantation without
      immunosuppression in animals receiving CsA induction therapy for their first
      transplant suggests that graft adaptation is not necessary for the maintenance of
      tolerance.

PMID- 8154023
TI  - Obviation of prereperfusion rinsing and decrease in preservation/reperfusion
      injury in liver transplantation by portal blood flushing.
AB  - Liver allografts are traditionally rinsed with cold lactated Ringer's (LR)
      prereperfusion to clear K(+)-rich preservation solution from the hepatic
      vasculature. LR has been shown, however, to be injurious to the graft. By
      restoring portal blood flow without rinsing and discarding the initial blood
      traversing the liver (PB flush), we sought to eliminate rinsing without inducing
      hyperkalemia. Between August 1988 and December 1992, 481 OLTx were performed in
      412 pts. Four rinsing methods were used sequentially: group 1 (157 pts)--low-flow
      rate cold LR rinse (500 ml, 100 ml/min via standard i.v. tubing at 100 cm H2O
      [LFLR]) during lower caval anastomosis; Group 2 (120 pts)--LFLR as in group 1, at
      reperfusion, 500 ml PB flush via IVC catheter; group 3 (66 pts)--high-flow-rate
      LR rinse (500 ml, 1 L/min using large-bore tubing with 100 cm H2O rinsing
      pressure [HFLR]), PB flush as in group 2; Group 4 (62 pts)--no LR rinse; PB flush
      as in groups 2 and 3. Poor early graft function (PEGF) was defined as peak ALT or
      AST > 2500 U or PT > 16 sec (on POD 2); PEGF causing re-OLTx or death within 14
      days was called primary nonfunction (PNF). Group 1 and Group 3 had high PEGF
      rates. Group 4 had significantly less PEGF than Group 1, with a trend toward a
      significant difference from Group 3. In Group 1, 3 pts. had intraoperative
      hyperkalemic cardiac arrest; this did not occur when PB flush was performed. PB
      flush without prior rinsing optimizes graft function without risk of
      hyperkalemia. LR rinse, alone or followed by PB flush, is unnecessary and may be
      deleterious.

PMID- 8154024
TI  - Enhancement of the recovery of rat hearts after prolonged cold storage by
      cyclocreatine phosphate.
AB  - The present study determined whether the administration of cyclocreatine
      phosphate (CCrP) prior to ischemia can enhance the recovery of rat hearts
      hypothermically preserved for a prolonged period. Rats (n = 6 per group) were
      injected intravenously with 1 ml saline or CCrP (500 mg/kg). After 2 hr, hearts
      were excised and arrested by an infusion of University of Wisconsin solution.
      Saline hearts were then incubated in 40 ml UW, while CCrP hearts were incubated
      in 40 ml UW containing 100 mg CCrP; a mixture that is now referred to as Hartford
      Hospital (HH) solution. After 6 hr of storage at 4 degrees C, hearts were
      reperfused in the Langendorff mode for 15 min and then in the working heart mode
      for 30 min. Results indicated that the recovery of cardiac function--measured as
      aortic flow, coronary flow, cardiac output, stroke volume, and stroke work--was
      significantly better in CCrP group (50-55% baseline) compared with that of saline
      hearts (20-25%). Although no difference in enzyme leakage (i.e., creatine kinase)
      or lactate was detected between the two groups, the increase in heart weight
      after the initial 6-hr storage was significantly higher in saline hearts compared
      with that of CCrP hearts. Results of this study support the conclusion that CCrP
      treatment provides improved functional recovery after prolonged hypothermic
      preservation.

PMID- 8154025
TI  - Effects of canine donor heart preservation temperature on posttransplant left
      ventricular function and myocardial metabolism.
AB  - The generally accepted method of preserving donor heart integrity during transfer
      is to arrest it with cold cardioplegic solution, then store it in a plastic bag
      immersed in an iced electrolyte solution. Temperatures between 0 degree C and 4
      degrees C are maintained by this method until the heart is transplanted. Although
      profound hyperthermia best inhibits metabolic processes, it may damage the
      myocardium. Higher myocardial temperatures may be more advantageous and may
      result in better preservation. The efficacy of this hypothesis has been
      investigated in a canine model. The hearts of 40 dogs were isolated, arrested
      with cold cardioplegia, removed from the animal, and stored at different
      temperature ranges from 0-3 degree C to 12-15 degrees C for 4 hr. After this time
      period, the hearts were transplanted into a recipient animal in the cervical
      heterotopic position. The degree and speed of myocardial functional recovery were
      monitored by measuring end-systolic elastance generated from pressure-diameter
      loops using sonomicrometry techniques. Myocardial metabolism was studied
      simultaneously by monitoring coronary flow, O2, glucose, lactate, pyruvate, and
      free fatty acid uptakes. The results were compared with those from a control
      group of hearts transplanted immediately after their removal. Our results
      indicate that donor heart function was significantly depressed 30 min after
      heterotopic transplantation, but returned to "control" levels after 2 hr when
      stored between 0 degrees C and 6 degrees C. Myocardial function remained
      significantly depressed throughout the 2-hr recovery period in hearts stored at
      higher (6-15 degrees C) temperatures. Hearts stored at all temperatures continued
      to extract glucose, lactate, and free fatty acids, but produced significantly
      higher levels of pyruvate at higher storage temperatures, which may be related to
      the favored use of free fatty acids. In conclusion, donor hearts stored at colder
      temperatures for 4 hr regain complete left ventricular function faster than
      hearts stored at higher temperatures. Our experiments support the presently
      applied methods of donor heart preservation for 4 hr.

PMID- 8154026
TI  - The impact of the quality of initial graft function on cadaver kidney
      transplants.
AB  - Living unrelated donor (LURD) transplants have immunologic barriers similar to
      cadaver transplants, yet the outcome is better (1-year graft survival = 96%). One
      advantage of LURD transplants is that, with the extremely short preservation
      time, the kidney functions immediately. We studied whether the quality of initial
      renal function affects the outcome of primary cadaver transplants. We divided 301
      non-6-antigen-matched recipients transplanted between 1/1/86 and 8/1/92--who had
      no graft loss due to hyperacute rejection, primary nonfunction, or technical
      reasons--into 5 groups based on the quality of initial renal function (serum
      creatinine level in the first week). We determined patient and graft survival
      rates for each group. We found that the quality of initial function had a
      significant effect on patient and graft survival rates. Recipients whose serum
      creatinine level was < 3 mg/dl on posttransplant day 5 (groups 1 and 2) had
      better patient and graft survival than either those whose serum creatinine level
      was > 3 mg/dl on day 7 (group 4) or those who required dialysis (group 5).
      Because some early dysfunction may be immunologic, we reanalyzed the data
      excluding patients with percent reactive antibody > or = 15; the quality of
      initial function in this group had a significant impact on outcome. Similarly,
      when patients with graft loss due to "death with function" were excluded, the
      quality of initial function had a significant impact on survival rates. We
      conclude that the quality of early posttransplant function is an important
      predictor of long-term outcome. Cadaver recipients with immediate good function
      have outcomes similar to living donor recipients. Our data suggest that increased
      effort should be made to improve immediate posttransplant function.

PMID- 8154027
TI  - Improvement in autonomic and gastric function following pancreas-kidney versus
      kidney-alone transplantation and the correlation with quality of life.
AB  - We conducted a series of studies to document changes in autonomic and
      gastrointestinal function following pancreas-kidney and kidney-alone
      transplantation, define how autonomic function is associated with quality of
      life, and identify how transplantation alters the quality of life of diabetic
      transplant recipients. Uremic type I diabetic patients receiving combined
      pancreas-kidney (n = 23) or kidney-alone (n = 16) transplants completed pre- and
      12-month-posttransplant evaluation of vasomotor function (total capillary pulse
      amplitude, capillary vasoconstriction response to cold, capillary response to
      postural adjustments), cardiac function (R-R interval variation, valsalva ratio),
      overall autonomic function (total autonomic score, autonomic index), gastric
      function (cutaneous electrogastrography, gastric emptying, total gastrointestinal
      symptoms score), and quality of life (sickness impact profile). Kidney recipients
      experienced nonsignificant improvement in autonomic function with significant
      improvement in total symptom score. In contrast, pancreas-kidney recipients
      demonstrated significant improvement in postural adjustment ratio (P < or =
      .0085), valsalva ratio (P < or = .0348), electrogastography (P < or = .0159), and
      total symptom score (P < or = .0001). Improvement or stabilization of gastric
      function occurred for 12 of 23 pancreas-kidney patients (52%) versus 5 of 12
      kidney-alone patients (41.7%). A path analysis of 56 diabetic patients having a
      wide range in diabetic autonomic neuropathy, found the sickness impact profile to
      correlate with valsalva ratio (r = .36, P < or = .0056), R-R interval (r = .27, P
      < or = .0396), and vasoconstriction (r = .24, P < or = .064). Together, autonomic
      function measures accounted for 15.2% of the total variance in the sickness
      impact profile. Sickness impact profile scores also significantly improved for
      both groups of transplant recipients.

PMID- 8154028
TI  - Retransplantation in hepatitis B--a multicenter experience.
AB  - Hepatitis B has become one of the most challenging diseases in liver
      transplantation. Infection of the allograft with subsequent graft failure is
      common and may prompt consideration of repeat liver transplantation. The aims of
      this study were to examine the experience in the United States with
      retransplantation in hepatitis B patients with recurrent disease as well as for
      other reasons. Questionnaires were mailed to adult liver transplant centers in
      the United States, requesting information on retransplantation in HBV patients.
      Responses were received from 71% of the centers. Thirty-eight patients were
      retransplanted, 20 for recurrent HBV and 18 for other reasons. The survival rate
      following retransplantation for HBV was poor. Nine patients (55%) died within 60
      days. Eleven patients survived 60 days or longer, though eight died at a mean of
      4.1 +/- 2 months, one required a third transplant for recurrent HBV infection at
      4 months, and one died at 35 months. Only a single (5%) long-term survivor
      exists. Recurrent histologic disease occurred earlier in the second transplant at
      2.8 +/- 2.9 months versus 6.1 +/- 5.2 months in the first allograft, though this
      difference did not reach statistical significance (P = .058). Patients
      transplanted for other reasons (primary non-function [9], hepatic artery
      thrombosis [6], persistent rejection [2], and a Pseudomonas graft infection [1])
      had a better survival rate. Four patients survived less than 60 days. Of the 14
      surviving longer than 60 days, 11 patients are alive at a mean of 21.2 +/- 14.8
      months. Retransplantation for recurrent HBV appears to be contraindicated due to
      a high mortality. Retransplantation in HBV patients with graft failure due to
      other causes, however, should be considered, since over 60% of these patients
      appear to have good long-term survival. Additional studies examining risk factors
      for recurrent disease should be considered.

PMID- 8154029
TI  - Transmission of hepatitis C by kidney transplantation--the risks.
AB  - The use of cadaveric organ donors with positive serologic tests for hepatitis C
      (HCV) has caused considerable debate. We have reviewed the clinical course of 43
      EIA1 HCV-negative recipients who received kidney transplants from EIA1 HCV
      positive donors (Study). We have attempted to define the rate of HCV-RNA
      transmission and to determine the frequency of HCV disease transmission as
      determined by abnormalities in liver function tests. Viral transmission was
      assessed using serologic assays for HCV antibody formation (EIA1, EIA2, and
      Matrix--an automated multiple antigen immunoblot assay) and with PCR testing for
      the presence of HCV-RNA on recipient sera. Liver function was followed
      longitudinally in the Study patients and compared with a group of 103 kidney
      recipients of organs from EIA1 HCV-negative donors (Control). Of the Study
      patients, 56% became PCR-positive for HCV-RNA, suggesting the transmission of HCV
      RNA from the HCV-positive donor. Interpretation of serologic tests for HCV was
      complex. Currently available first (EIA1) and second (EIA2) generation serologic
      assays were always negative. The multiple antigen immunoblots assay (Matrix) had
      a high positive predictive value (93%) for the presence of HCV-RNA transmission,
      but one-third of Matrix-negative Study patients were PCR-positive (sensitivity =
      66%). Currently, only 38% of recipients have HCV-RNA, suggesting that the virus
      may have been cleared by one-third of Study recipients who had circulating virus.
      Traditional tests of liver function (ALT, AST, AP, and GGT) were of limited use
      in predicting HCV-RNA transmission. Average AST, AP, and GGT were similar in the
      two groups. Average ALT was increased (93 I/U and 47 I/U) in Study and Control
      patients, respectively, but this difference was not significant. Episodes of
      abnormal liver function (ALT 60-99 IU for > or = 14 days) occurred in 22% of
      Study and 10% of Control patients (P = NS) and lasted longer in Study compared
      with Control patients (301 vs. 138 days; P < 0.02). Hepatitis (ALT > or = 100 IU
      for > 14 days) occurred with an equal frequency (6.5%) in both groups. The
      presence of HCV-RNA did not predict episodes of abnormal liver function.
      Fulminant hepatitis or rapidly progressive cirrhosis did not occur in the
      recipients of organs from HCV-positive donors. These data demonstrate a high
      efficiency of transfer of HCV-RNA by kidney transplantation from an HCV-positive
      donor to an HCV-negative recipient. A majority of the patients have asymptomatic
      HCV infection.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8154030
TI  - Depletion of hepatitis C virus from procured kidneys using pulsatile perfusion
      preservation.
AB  - The safety of the use of kidneys procured from a hepatitis C virus (HCV)-positive
      cadaver donors in transplantation has recently been the subject of controversy.
      One factor that is important in determining the transmission of the virus and/or
      viral liver disease is the total viral inoculum to which the renal allograft
      recipient is exposed as a result of the transplant. We have studied the effect of
      a standard pulsatile renal preservation procedure and variations of it on the
      number of viral copies in organs from HCV-positive donors. An HCV-RNA
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) method was
      utilized with a recombinant competitive inhibitor substrate added after cDNA
      synthesis with the PCR primers within the relatively non-polymorphic 5'
      untranslated region of the HCV genome. Additionally, strain specificity was found
      to be detectable using a modification of the technique of restriction fragment
      length polymorphism (RFLP-PCR), so that virus from the organ donor could be
      specifically identified and quantified in the recipient. It was observed that
      standard preservation procedures using pulsatile perfusion were able to eliminate
      75% of the virus from the organ in 20 hr. By modifying this procedure to include
      additional wash steps and a second pulsatile perfusion, greater than 99% of the
      virus could be eliminated from the kidney. In a related study, we used
      quantitative PCR to study requirements for filtration of the virus using HCV
      positive serum. It was found that a high-flow-rate ultrafilter with a molecular
      weight cut-off (MWCO) of 300,000 daltons placed in series to the preservation
      apparatus was very efficient in eliminating the virus from perfusion solution in
      less than 2 hr. It can therefore be proposed that with the use of these molecular
      techniques, pulsatile perfusion coupled with additional viral depletion steps
      (dilution, and/or filtration) may allow the practical reduction of HCV
      transmission risk in recipient follow-up studies. The means are thereby presented
      for similar manipulation of other known or, as yet, unknown transmissible agents.

PMID- 8154031
TI  - Peripheral blood chimerism in renal allograft recipients transfused with donor
      bone marrow.
AB  - Experimental studies have shown that administration of antilymphocyte serum
      combined with donor bone marrow cells can induce tolerance to allograft tissue.
      We have initially reported application of these protocols in clinical studies of
      cadaveric renal allograft recipients who were treated with MALG and donor
      specific bone marrow cells. To evaluate the effectiveness of the donor marrow
      cells in the production of chimerism, a detection method based on 32P
      incorporated PCR was established. The 32P PCR was utilized with primers specific
      for the HLA class II, VNTR (D17S5 and D1S111), and/or Y-chromosome genes to
      detect the presence of allogeneic chimerism in the recipients. Immediately
      posttransplant, 26.4% of marrow recipients demonstrated the presence of
      allogeneic chimerism prior to the marrow transfusion as did 18% in the
      untransfused controls. In transfused patients, chimerism was detected most
      frequently during the 1-3-month interval after marrow transfusion (65%), and then
      diminished to 50-56% at 3-12 months posttransfusion. In the control group the
      frequency of allogeneic chimerism was gradually decreased and was undetectable in
      the majority of the patients beyond 3 months posttransplant while marrow
      transfused recipients were more likely to have chimeric cells detected
      consistently beyond 3 months. Rejection episodes were significantly effected by
      the presence of chimerism in the recipients. Of the transfused patients, 91.3%
      who demonstrated allogeneic chimerism were rejection-free as compared with 8.7%
      who experienced at least one rejection episode (P = 0.01). While the presence of
      allogeneic chimerism in the control group was correlated with rejection-free
      graft survival, this difference did not reach statistical significance.

PMID- 8154032
TI  - The impact of an acute rejection episode on long-term renal allograft survival
      (t1/2).
AB  - An acute renal transplant rejection episode has been shown to be associated with
      decreased 1-year graft survival. The impact on long-term outcome is undefined. We
      studied the impact of an acute rejection episode on t1/2, the time it takes for
      1/2 of the grafts functioning at 1 year to fail. Use of t1/2 avoids inclusion of
      early graft loss to acute rejection or complications of treatment. Since 1/1/86,
      a total of 653 patients have received a primary kidney transplant and had at
      least 1 year of function. Recipients were divided by the incidence and timing of
      rejection: no rejection; 1 rejection within the first year; > 1 rejection, the
      first episode in the first year; and > or = 1 rejection, the first episode after
      the first year. A single rejection episode in the first year reduced t1/2 (45 +/-
      11 years in those with no rejection vs. 25 +/- 8 years in those with 1 in the
      first year). Multiple rejections (t1/2 = 5 +/- 11 years) and a first rejection
      after the first year (t1/2 = 3 +/- 1 years) have a significant effect (P < .05).
      Both living and cadaver donor recipients with rejection had shortened t1/2. For
      those with > 1 rejection, the first episode in the first year, and those with >
      or = 1 rejection, the first episode after the first year, chronic rejection was
      the predominant cause of graft loss; noncompliance also played a role. We
      conclude that a single rejection episode shortens t1/2. Those with > 1 rejection,
      the first episode within the first year, and those with > or = 1 rejection, the
      first episode after the first year, are at high risk for late graft loss.

PMID- 8154033
TI  - Reduction of cyclosporine-induced nephrotoxicity by cilastatin following clinical
      heart transplantation.
AB  - The objective of this prospective, randomized, placebo-controlled, single-blinded
      study in 28 heart-transplanted patients was to investigate whether the
      dehydropeptidase inhibitor cilastatin reduces cyclosporine-induced
      nephrotoxicity. Cilastatin is available only in combination with imipenem, a beta
      lactam antibiotic to which it is added for reduction of nephrotoxic side-effects
      of the antimicrobial agent. Patients received either 100 ml placebo (n = 12) or
      100 ml (500 mg) imipenem/cilastatin (n = 16) twice perioperatively, and 4 times
      daily for the first 7 postoperative days. Serum creatinine and urea, as well as
      urine concentrations of N-acetyl-beta-D-glucosaminidase, which is directly
      correlated with tubular cell damage, were used as markers for renal function.
      Thromboxane B2 and 6-keto-prostaglandin F1-alpha serum concentrations were
      determined to investigate whether there is an imbalance in synthesis of
      thromboxane A2 and prostacyclin as a possible mechanism for cyclosporine-induced
      nephrotoxicity. Two placebo patients and 6 patients receiving imipenem/cilastatin
      had to be excluded from further analysis. Three of 10 placebo patients required
      hemofiltration, and 2 of them even required hemodialysis, as compared with none
      in the imipenem/cilastatin group. Creatinine concentrations increased
      significantly from the second to the fourth postoperative day in the placebo
      group, but remained nearly normal in cilastatin patients (P < 0.05 for intergroup
      comparison on postoperative days 2-4). The same trend was observed in urea and N
      acetyl-beta-D-glucosaminidase concentrations, without the difference reaching
      statistical significance. For thromboxane B2 and 6-keto-prostaglandin F1-alpha no
      differences between the groups could be found. These results suggest that
      imipenem/cilastatin can counteract acute cyclosporine-induced nephrotoxicity,
      which appears to be associated with alterations of tubular cell function. The
      combined use of cyclosporine and imipenem/cilastatin appears to be advantageous
      in patients following heart transplantation during the initial postoperative
      period.

PMID- 8154034
TI  - Effect of donor age on outcome of kidney transplantation. A two-year analysis of
      transplants reported to the United Network for Organ Sharing Registry.
AB  - The shortage of cadaveric donors coupled with a rapidly growing number of
      potential recipients has resulted in an increased use of older donors. In 1992,
      10.7% of all cadaveric kidney transplants were from donors above the age of 55
      compared with 5.4% in 1988. The present investigation serves as a follow-up of a
      prior study of the effect of donor age on outcome with a 2-year analysis of more
      than 30,000 cadaveric kidney transplants performed in the United States between
      October 1, 1987, and December 31, 1991, that were reported to the United Network
      for Organ Sharing. There was no difference between the graft survival at 1 and 2
      years comparing donors aged 56-65 versus 65 and older, but the older donors (aged
      56 and greater) had a 1- and 2-year graft survival that was approximately 10% and
      14% less than that for recipients from the ideal age group of donors (16-45
      years). There was no practical adverse interaction between donor age and
      recipient age, gender, diabetic status, peak PRA (panel reactive antibody
      activity) level of mismatch, cold ischemia time, or recipient race on outcome.
      The kidneys from older donors had poorer graft survival than the kidneys from
      younger donors when transplanted into recipients of repeat transplants, though
      the impact of repeat transplant and donor age on graft survival are independent
      of one another. These data suggest that kidneys from donors over the age of 55
      overall have reduced functional reserve, which has an adverse effect on long-term
      function. Thus, attempts should be made to better estimate functional reserve
      among the older age group, but age alone should not be the sole factor for
      exclusion of a potential donor. The use of older donors appears to present an
      increased but acceptable risk of graft loss 2 years after transplant.

PMID- 8154035
TI  - A prospective randomized study of acyclovir versus ganciclovir plus human immune
      globulin prophylaxis of cytomegalovirus infection after solid organ
      transplantation.
AB  - Cytomegalovirus disease occurs frequently after solid organ transplantation and
      has been associated with decreased patient and allograft survival. We
      hypothesized that CMV transmission or reactivation begins immediately or soon
      after transplantation, and that a short-duration ganciclovir (GCV)-based regimen
      would obviate the need for long-term antiviral agent administration, perhaps
      serving to interdict CMV infection and disease as well as, or perhaps even more
      effectively than, a more prolonged, oral acyclovir (ACV)-based form of
      prophylaxis. A total of 311 patients were stratified according to allograft type,
      age, and presence or absence or diabetes mellitus, and were then randomized to
      receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d.
      for 12 weeks after transplantation or 6 weeks after any antirejection therapy)
      versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or
      after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin
      or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7
      after transplant or after any antirejection therapy. A total of 266 patients
      (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for
      follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV
      group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group
      developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than
      those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate
      analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis
      demonstrated that receiving antirejection therapy, a liver transplant, or a donor
      organ from a CMV-seropositive individual if the recipient was CMV seronegative
      were major risk factors for the development of CMV disease (P < 0.001), while the
      difference between ACV versus GCV + HIg prophylaxis was also significant (P =
      0.054). No differences in actuarial patient or allograft survival, however, were
      noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be
      more effective in reducing the incidence of posttransplant CMV disease, although
      this effect was diminished in high-risk groups of patients. Our findings indicate
      that CMV transmission or reactivation may best be prevented by long-term
      antiviral agent administration, and that the primary morbidity of CMV disease is
      the need for rehospitalization when either prolonged ACV or short-duration GCV +
      HIg prophylaxis is used in this patient population.

PMID- 8154036
TI  - The relationship among donor-recipient HLA mismatches, rejection, and death from
      coronary artery disease in cardiac transplant recipients.
AB  - Review of 448 cyclosporine-treated heart transplant recipients was undertaken to
      examine the relationship of donor-recipient HLA compatibility to patient
      survival, rejection, and death from coronary artery disease (CAD). Pre-Tx
      crossmatching and panel-reactive antibody (PRA) were correlated to survival as
      well. Overall patient survivals were 78%, 70%, and 65% at 1,3, and 5 years post
      Tx, respectively. Matching of donor-recipient HLA did not improve outcome in that
      1,3, and 5 years survivals for well-matched (< or = 2 A, B, or 0-1 DR mismatches
      [MMs]) vs. poorly matched (> 2 A, B, or 2 DR MMs) recipients were comparable and
      not significantly different. Well-matched recipients, however, experienced
      significantly fewer rejections (1.06 +/- 1.2 vs. 1.96 +/- 1.0, P < 0.01 for < or
      = 2 A, BMMs vs. > 2 A, B MMs and 1.1 +/- 0.9 vs. 2.0 +/- 1.1 for 0-1 DR MMs vs. 2
      DR MMs, P < 0.01). Moreover, HLA-DR, but not HLA A, B was a significant (P <
      0.01) predictor of early rejection (<30 days) in that 65% (165/254) of poorly
      matched vs. only 40% (95/194) of well-matched HLA-DR recipients experienced early
      rejections. Interestingly, an inverse relationship was found between HLA A and B
      MM, but not HLA-DR MM, and death from coronary artery disease in that 17% (19/11)
      of well matched vs 9% (32/327) of poorly matched patients died from CAD. Pre-Tx
      PRA did not impact patient survival or rejection. Donor-recipient crossmatching
      was performed utilizing the NIH and/or antiglobulin (AHG) procedures. No survival
      differences were observed at 1, 2, and 3 years post-Tx when comparing outcome for
      the 24 NIH crossmatch (XM)-positive (+) with the 424 NIH-XM-negative displayed a
      positive AHG recipient antidonor displayed a positive AHG recipient antidonor
      reactivity. When these 10 AHG-XM (+) sera were treated with dithioerythritol (to
      inactivate IgM) all 10 converted to a negative reactivity, indicating that a
      positive crossmatch due to IgM reactivity should not be considered a
      contraindication to cardiac transplantation. These data also suggest that the
      reactivity of the 24 NIH-XM(+) sera were most likely due to IgM, and that poorly
      matched heart recipients may benefit from a more aggressive immunosuppressive
      regimen to prevent early rejections.

PMID- 8154037
TI  - A preliminary report of diltiazem and ketoconazole. Their cyclosporine-sparing
      effect and impact on transplant outcome.
AB  - A prospective randomized trial was conducted to compare the effect of diltiazem
      (DILT) with ketoconazole (KETO) on sparing of cyclosporine dose and renal
      transplant outcome. Renal allograft recipients 18 years old and older were
      eligible for the study. Triple immunosuppression (TRIPLE) including prednisone,
      azathioprine, and CsA was administered to all patients. The maintenance CsA dose
      varied by study group. Patients were randomized to receive one of three treatment
      strategies: group 1-TRIPLE (CsA 8 mg/kg/day); group 2--TRIPLE (CsA 6 mg/kg/day) +
      DILT (60 mg b.i.d.); group 3--TRIPLE (CsA 3 mg/kg/day) + KETO (200 mg/day).
      Modification of the DILT dose was allowed as needed to effect blood pressure
      control in group 2 patients. Mean 1-month CsA dose reductions were 30% and 60% of
      controls in group 2 and 3, respectively. A continued effect over time was
      observed in patients administered KETO but not DILT. At 1 year patients taking
      KETO required an average of 77% less CsA than the average dose necessary to
      effect similar parent CsA blood levels when no enzyme inhibitor was used. The use
      of KETO and DILT for 1 year allowed for 53% and 14% reductions in CsA cost,
      respectively. These savings include the cost of the KETO or DILT. Serum
      creatinines, mean arterial pressure (MAP), and incidence of liver function
      abnormalities were similar throughout treatment groups. The rate of rejection,
      time to rejection onset, and survival (GS/PS) were not different among the
      groups. Fungal infections were fewer in patients treated with KETO (12%) than in
      controls (16%) and patients randomized to DILT (19%). KETO failed to prevent
      Aspergillus infection in one individual. The investigation failed to identify any
      harmful result of treating renal allograft recipients with either DILT or KETO
      for the purpose of reducing CsA expense.

PMID- 8154038
TI  - A role for transforming growth factor-beta in the veto mechanism in transplant
      tolerance.
AB  - We have studied the veto cell-mediated induction of transplant tolerance by
      allogeneic donor bone marrow cells and have achieved kidney allograft tolerance
      in a preclinical rhesus monkey model. Here we extend these studies to investigate
      the veto mechanism of CTLp suppression and the role of CD8 and TGF-beta in these
      events. Infusion of DR-/dim donor BMC into RATG-treated rhesus monkeys induced
      functional deletion of donor-specific CTLp and prolongation of kidney allograft
      survival, whereas depletion of the CD8+ subset from BMC ablated these effects. A
      role of CD8 in the veto effect was further implicated by rhesus MLR-induced CML
      experiments in which pretreatment of normal responder cells with MAb to MHC class
      I, the natural ligand of CD8, blocked the suppressive activity of allogeneic BMC.
      In addition, pretreatment of the BMC with anti-CD8 MAbs blocked strong veto
      activity significantly, suggesting that CD8 functions as an accessory or adhesion
      ligand. In contrast, anti-CD8 treatment significantly enhanced weak BMC-mediated
      veto activity, suggesting that CD8 might additionally serve as a signal
      transducer to increase veto activity, perhaps by the induction of cytokine
      release. The cytokine TGF-beta was studied because it has immunosuppressive
      properties that are shared by veto cells. Human TGF-beta, like BMC veto cells,
      inhibited MLR-induced CML in a dose-dependent manner, and anti-TFB-beta Ig
      relieved the BMC-mediated veto suppressive effect. Active TGF-beta was detected
      only in the supernatants of CML cultures containing BMC. Pretreatment of BMC with
      L-leucyl-leucine methyl ester (Leu-leu-OMe), which eliminates cytotoxic precursor
      and effector lymphocytes and monocytes, did not affect levels of active TGF-beta.
      In previous studies, the veto effect of BMC was also shown to be Leu-leu-OMe
      resistant. Finally, treatment of isolated DR-/dim BMC cultures with anti-CD8
      elicited TGF-beta secretion, whereas anti-CD2 or anti-CD3 had no effect. When
      isolated after stimulation with anti-CD8, only the CD8+ subset of DR-/dim BMC
      produced detectable levels of active TGF-beta. In summary, these studies
      demonstrate that CD8 functions as an immunoregulatory molecule in veto effects by
      freshly isolated rhesus BMC and suggest that CD8-ligand interactions may induce
      low-level secretion of TGF-beta to mediate or facilitate the veto mechanism of
      CTLp inactivation in a paracrine manner.

PMID- 8154039
TI  - Neutrophil adhesion and complement inhibition prolongs survival of cardiac
      xenografts in discordant species.
AB  - Hyperacute rejection results in rapid destruction of a discordant cardiac
      xenograft and is characterized by antibody deposition, complement activation, and
      platelet aggregation. The importance of neutrophils is unclear. Complement
      inhibition prolongs discordant cardiac xenograft survival. The purpose of this
      experiment was to determine the relative roles of complement and neutrophils.
      Selective inhibition of complement and neutrophil adhesion was used in a guinea
      pig-to-Lewis rat cardiac heterotopic xenotransplant model. NPC 15669 (N-[9H-(2,7
      dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine), a member of a new class of
      antiinflammatory agents termed leumedins, specifically prevents recruitment of
      neutrophils at inflammatory foci by inhibiting upregulation of the CD11b/CD18
      adhesion molecule. Soluble complement receptor type 1 (sCR1, BRL 55730) is a
      potent inhibitor of the alternative and classical complement pathways. Group I (n
      = 13) received saline vehicle i.v. Group II (n = 15) was treated with NPC 15669
      (10 mg/kg i.v. bolus) prior to reperfusion. Group III (n = 13) was treated with
      sCR1 (20 mg/kg i.v. bolus) prior to reperfusion. Group IV (n = 13) received both
      NPC 15669 and sCR1. Two xenografts were harvested at each interval time point
      (Groups I and II, 1, 2, 4, and 6 min; and Groups III and IV, 6, 15, 30, and 60
      min). The remainder were followed to cessation of graft function. Graft survival
      was significantly increased in group IV and group III-375 +/- 13.4 min (mean +/-
      SD) and 112 +/- 29.4, respectively (P < .05), compared with 9.9 +/- 6.3 in group
      II and 8.7 +/- 4.9 in group I. Extreme interstitial hemorrhage and edema and
      contraction band injury were present in group I-III animals at end-stage, and
      neutrophil infiltration in group III. In group IV grafts, there was a decrease in
      these parameters despite the longer survival time, and at end-stage rejection the
      cellular infiltrate was primarily mononuclear. This study demonstrates that
      complement is an important mediator in early xenograft HYP injury. Combined
      treatment with NPC 15669 and sCR1 results in reduced histologic injury at all
      time points and longer graft survival than with sCR1 alone. These results suggest
      that neutrophil and complement activation play synergistic roles in the
      pathogenesis of xenograft hyperacute rejection. Neutrophil inhibition may prove
      to be an important component of multimodality therapy for hyperacute rejection,
      particularly in less-discordant transplants.

PMID- 8154040
TI  - Donor species complement after liver xenotransplantation. The mechanism of
      protection from hyperacute rejection.
AB  - Hamster hearts transplanted into stable rat recipients of hamster livers (OLT
      rats) were hyperacutely rejected after transfer with unaltered rat antihamster
      hyperimmune serum (HS). This was followed by immediate liver xenograft rejection
      in 4 of 5 rats. In contrast, simple heat inactivation of the rat HS resulted in
      prolonged survival of hamster hearts to 25 days without deterioration effect in
      the liver xenografts. This effect was species-specific because third-party mouse
      heart grafts in OLT rats were hyperacutely rejected in minutes if either active
      or heat inactivated antimouse HS was given. In cytotoxicity experiments, the
      complement in OLT serum produced weak lysis of hamster lymphocytes, while
      efficiently doing so with mouse cell targets. Because normal hamster serum caused
      no lysis at all of hamster target cells, the residual low-grade lysis of OLT
      serum was possibly being mediated by extrahepatic sources of rat C. In
      conclusion, the homology of C and target cells represents a mechanism of
      protection that the liver confers to other organs, and that is mostly easily seen
      in xenografts but may be allospecifically operational with allografts as well
      within the limits of MHC restriction.

PMID- 8154041
TI  - The role of anti-pig antibody in pig-to-baboon cardiac xenotransplant rejection.
AB  - The role of naturally produced antibody in discordant xenograft rejection is
      still uncertain. Twelve orthotopic pig-to-baboon heart transplants (HTx) were
      performed. In 2 baboons, no antibody adsorption (AbA) was performed. In 5
      baboons, AbA with a pig lung was performed during circulatory arrest. In 5
      baboons, AbA and blood exsanguination at the beginning of cardiopulmonary bypass
      (CPB) were performed. Baboons were divided into 2 groups; group 1 (n = 4) died
      within 24 hr of HTx and group 2 (n = 8) survived more than 24 hr. Mean survival
      period was 9.8 +/- 3.0 hr in group 1 and 151 +/- 33 hr in group 2. Baboon anti
      pig antibody (Ab) was measured before CPB, before circulatory arrest, during AbA,
      at the end of CPB, and daily after HTx. Anti-RBC Ab was measured by the titration
      method at temperatures of 4 degrees C and 37 degrees C (RAb-4 and RAb-37). Anti
      endothelial cell Ab (EAb) and anti-white blood cell Ab (WAb) titers were measured
      with ELISA. RAb titration > or = 1/4 and EAB and WAb > or = 1/256 were determined
      to be seropositive (S(+)). S(+) rate of RAb-37 at the end of CPB (endCPB) in
      group 2 was significantly higher than that in group 1 (8/8 vs. 1/4; P < 0.05).
      The seronegative (S(-)) rates of RBC-4 and EAb (endCPB) in group 2 were higher
      than those in group 1 (7/8 vs. 1/4 and 6/8 vs. 1/4, respectively), but not
      significantly. There was no difference in S(-) rate of WAb (endCPB) between group
      1 and group 2. More than 4-fold decrease in RAb-4 and RAb-37 by AbA with a pig
      lung was observed in 5 and 7 of 8 baboons, while EAb and WAb did not change by
      AbA. In all of group 2, RAb-4 reverted to S(+) within 3 days after HTx. One
      baboon had no rejection episode and died of infection 16 days after HTx (baboon
      16); however, it also became S(+) for RAb-4 a day after HTx until death. In 4 of
      group 2, RAb-37 became S(+) 1 or 2 days before death by rejection. Baboon 16,
      however, became S(+) for RAb-37 7 days after HTx and S(-) again 9 days after HTx
      until death. EAb became S(+) in all of group 2, but 5 of them survived more than
      5 days after seroconversion.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8154042
TI  - The increased efficacy and decreased nephrotoxicity of a cyclosporine liposome.
AB  - A potential approach to avoid the complications of systemic immunosuppression is
      to deliver immunosuppressive agents locally to the site of the allograft.
      Liposomes are phospholipid particles that allow delivery of drugs preferentially
      to the reticuloendothelial system. Since the liver is a primary component of the
      RES, we hypothesized that liposome technology could be utilized to deliver
      immunosuppressive agents locally to a transplanted liver, thereby avoiding the
      complications of systemically delivered immunosuppression. We evaluated this
      hypothesis with a prototypic cyclosporine liposome in a rat model.
      Pharmacokinetic studies of this liposome indicated earlier clearance from the
      systemic circulation and increased hepatic uptake relative to the standard
      intravenous form of CsA. Decreased nephrotoxicity was also shown in an ischemic
      kidney model in the rat. The immunosuppressive efficacy of this liposome was also
      tested in a rat liver transplant model. There was a significant increase in
      survival compared with standard intravenous CsA when both drugs were administered
      at a dose of 1.75 mg/kg/day for seven days posttransplant (P < .05, CsA liposome
      treated versus CsA/saline-treated). There were no demonstrable early toxic
      effects or late toxic effects observed with follow-up to 100 days. These data
      indicate that CsA liposomes have potential for use as an immunosuppressive agent
      with increased efficacy and decreased nephrotoxicity relative to the commercially
      available form of intravenous CsA. This improved therapeutic index of a locally
      targeted drug may lead to fewer complications attributed to systemic
      immunosuppression.

PMID- 8154043
TI  - Abrogation by rapamycin of accelerated rejection in sensitized rats by inhibition
      of alloantibody responses and selective suppression of intragraft mononuclear and
      endothelial cell activation, cytokine production, and cell adhesion.
AB  - This study evaluated the efficacy and mode of action of rapamycin (RPM) in a
      model of accelerated (24-hr) rejection of LBNF1 cardiac allografts in
      specifically sensitized LEW rats. RPM treatment (0.25 mg/kg/day i.p.) between the
      day of sensitizing skin grafts (day -7) and subsequent heart (day 0)
      transplantation (Tx), abrogated fulminant rejection and prolonged cardiac
      allograft survival to 46 +/- 22 days (mean +/- SD, P < 0.0001). The delayed
      introduction of RPM until day -2 or day -1 was equally effective, whereas
      treatment initiated after cardiac Tx was ineffectual. Untreated accelerated
      rejection was associated with strong production of circulating IgM, whereas an
      IgG alloantibody response was not detected until after rejection was complete.
      RPM therapy (day -7 to -1) diminished this systemic IgM response and prevented
      the switch from IgM to IgG alloantibody production. Immunohistologic evaluation
      at 24 hr after cardiac Tx showed that compared with untreated hosts RPM treatment
      largely abolished intragraft cellularity, and was associated with decreased
      mononuclear and endothelial cell activation. Specifically, Ia and ICAM-1
      upregulation was abolished, and no cells elaborating IL-2 or IFN-gamma were
      detected. In addition, RPM treatment prevented intragraft production of the
      proinflammatory cytokines IL-1 beta, IL-6, and IL-8. The effects of RPM therapy
      on recipient cellular responses were evaluated in vitro by mixed lymphocyte
      reaction. Surprisingly, the donor-specific proliferative response of cells from
      RPM-treated hosts at 1 or 7 days after Tx was markedly increased, compared with
      cells from rejecting, untreated controls, and bioassay of IL-2 within
      supernatants of MLR cultures showed comparable levels of IL-2 in both groups. The
      effects of RPM upon adhesion properties of lymph node lymphocytes were also
      tested in an in vitro binding assay. The binding of naive cells to sections of
      cardiac allografts collected from RPM-treated hosts at 24 hr post-Tx was
      decreased compared with that in untreated recipients. Interestingly, the binding
      of mononuclear cells to high endothelial venules of peripheral lymph nodes in RPM
      treated hosts remained relatively high. Thus, treatment with RPM prevents and/or
      erases the sensitization, which otherwise leads to accelerated allograft
      rejection. Abrogation of allograft injury by RPM was associated with profound and
      long-lasting depression of host IgM and IgG alloantibody responses in the
      circulation, and selective downregulation of host cellular immunity and
      endothelial activation at the graft site. In contrast, antigen alloreactivity and
      endothelial adhesivity in peripheral lymphoid tissues were spared, indicating
      novel and potent selective effects of RPM therapy in allograft recipients.

PMID- 8154044
TI  - The absence of constitutive and induced expression of critical cell-adhesion
      molecules on human cardiac myocytes. Its role in transplant rejection.
AB  - Fetal human cardiac myocytes (FHCM) and a cell line derived from FHCM, termed W1,
      constitutively express low levels of MHC class I antigens and significant levels
      of ICAM-1 (CD54), and LFA-3 (CD58) but do not express LFA-1 alpha (CD11a), LFA-1
      beta (CD18), GMP-140 (CD62), BB1-B7, VCAM-1, and ELAM-1. In vitro incubation of
      FHCM or the W-1 cell line for varying periods with varying concentrations of IFN
      gamma, TNF-alpha, Poly IC, LPS, IL-alpha, IL-1 beta, PMA, PDBu, and supernatant
      fluids from Con A-activated PBMC or allogeneic MLR cultures failed to induce cell
      adhesion molecules (CAMs) or costimulatory molecules that are not constitutively
      expressed on these cells except for MHC class II antigens. In addition, IFN
      gamma, Con A, and MLR supernatant fluids (in order of biological activity) not
      only induced MHC class II antigens but also markedly increased the mean density
      of expression per cell of MHC class I and ICAM-1. Analysis of the stability of
      MHC class I/II molecules using agents like brefeldin-A and Western blot analysis
      of MHC class II molecules suggest that these ligands are very stably expressed on
      myocytes. Our previous studies have documented the failure of MHC-expressing FHCM
      to induce an alloproliferative response. The results of the present studies show
      that this failure is not secondary to the absence of ICAM-1 or LFA-3 or the
      presence of unstable MHC molecules but is most likely due to the absence of other
      CAMs/costimulatory molecules that are critically required for inducing allogeneic
      activation.

PMID- 8154045
TI  - The failure of intrathymic transplantation of nonimmunogenic islet allografts to
      promote induction of donor-specific unresponsiveness.
AB  - Freshly isolated allogenic pancreatic islets transplanted into the thymus of
      transiently immunosuppressed rats are not rejected but survive indefinitely while
      also inducing a state of specific unresponsiveness that permits survival of
      secondary donor-strain islets transplanted extrathymically. Since freshly
      isolated pancreatic islets contain intraislet antigen-presenting cells as well as
      endocrine cells it is unclear which cellular component is primarily responsible
      for mediating unresponsiveness. We therefore examined the impact of pretransplant
      in vitro culture (a maneuver which selectively depletes intraislet APCs) on the
      capacity of islet allografts to induce unresponsiveness after intrathymic
      implantation. APC-depleted pancreatic islets, which are known to have reduced
      immunogenicity, survived indefinitely in the thymus of allogeneic hosts whether
      or not brief immunosuppression was employed, but failed to promote survival of
      subsequent donor-strain islets transplanted to an extrathymic site. These
      findings emphasize the central role of APCs in the induction of transplantation
      tolerance in this model, and are consistent with the established role of this
      population in the development of T cell tolerance in the thymus.

PMID- 8154046
TI  - Protection of pig kidney (PK15) cells from the cytotoxic effect of anti-pig
      antibodies by alpha-galactosyl oligosaccharides.
AB  - Anti-pig antibodies in human and baboon serum are believed to be directed against
      alpha-galactosyl (alpha Gal) epitopes expressed on various pig cells, including
      vascular endothelia. We have investigated the effect of human sera on the PK15
      pig kidney cell line, which abundantly expresses alpha Gal epitopes. To
      quantitate cell viability, we have used a staining method that differentiates
      live cells from dead ones. Various carbohydrates (n = 28) were added individually
      to serum at concentrations of 0.125-50 mg/ml. Unmodified serum caused approximate
      100% PK15 cell death within 60 min. Carbohydrates that were not alpha Gal based
      did not significantly protect PK15 cells. Of the alpha Gal-based carbohydrates,
      only B disaccharide protected PK15 cells from both human and baboon serum (76%
      and 93% protection, respectively, at 1 mg/ml). Three alpha Gal oligosaccharides
      provided approximately 80-90% protection against both human and baboon sera at a
      concentration of 10 mg/ml. Three other closely related structures protected only
      against baboon serum (> 80%) at high concentration (50 mg/ml), suggesting a
      difference in anti-pig antibody affinity between baboon and man. Specific anti
      alpha Gal antibody-depleted serum caused < 10% pig cell death, whereas the
      antibodies eluted from the alpha Gal columns caused > 70% pig cell death. In
      conclusion, this study provides further evidence that (1) alpha Gal structures
      are the targets for human and baboon anti-pig antibodies, and (2) there may be a
      therapeutic role for the infusion of specific alpha Gal carbohydrates, or for
      antibody removal using alpha Gal immunoaffinity columns, in order to prevent
      hyperacute rejection of pig organs in man.

PMID- 8154047
TI  - Identification of patients at risk for inferior renal allograft outcome by a
      strongly positive B cell flow cytometry crossmatch.
AB  - To evaluate the influence of a positive B cell flow cytometry crossmatch (FCXM)
      on transplant outcome, we retrospectively performed B cell FCXMs for 431
      consecutive cadaver renal transplant recipients using the two most current
      pretransplant sera. All transplant recipients had a negative lymphocytotoxic
      antiglobulin T cell XM and a negative (< or = 10 channel shift) T cell FCXM. B
      cell FCXMs were performed using a two-color technique to identify binding of IgG
      antibody to donor lymph node B lymphocytes stained for CD20. The incidence and
      causes of graft failure posttransplant were determined by requesting this
      information from recipient transplant centers. Transplants that failed due to
      nonimmunological causes (n = 54, 13%) were excluded from the analysis. Minimum
      follow-up was 12 months. We found no difference in graft survival at one year for
      transplants where the B cell FCXM was positive in the range of 11 to 50 channel
      shift (n = 201) compared with those with a negative (< or = 10 channel shift) B
      cell FCXM (n = 141)--i.e., 90% vs. 91%, P = NS. However, when the positivity in
      the B cell FCXM was > 50 channel shift (n = 35), significantly fewer grafts
      survived at one year, compared with those where the channel shift was < or = 50
      (n = 342), 63% vs. 91%, P < 0.001. This was true for first transplants as well as
      regrafts and for transplants performed with a positive as well as a negative
      standard B cell XM. The detrimental effect of a positive B cell FCXM was seen for
      sensitized (PRA > 10% at the time of transplant) as well as nonsensitized
      patients. However, this effect was observed only when the donor had at least a
      one-DR mismatch. We conclude that a strongly positive B cell flow cytometry
      crossmatch identifies patients who are at risk for graft loss. Since the risk
      appears to be only when there is a DR mismatch, the data suggest that the B cell
      specific IgG antibody detected by flow cytometry may be specific for the
      mismatched MHC class II antigens of the donor.

PMID- 8154048
TI  - Transmission of CNS malignancy by organ transplantation.

PMID- 8154049
TI  - The synergistic effect of combined antibody and complement depletion on
      discordant cardiac xenograft survival in nonhuman primates.

PMID- 8154050
TI  - [The induction of mutations in 6-mercaptopurine resistance in Chinese hamster
      cells under the action of the recombinant plasmid pAins containing the human
      insulin gene].
AB  - The mutagenic activity of the pUC19 bacterial plasmid DNA and the pAins
      recombinant plasmid DNA carrying human insulin gene has been investigated. Both
      pUC19 and pAins plasmid DNAs have been shown to induce the gene mutations in hprt
      locus of Chinese hamster cell line. The high level of the gene mutations (similar
      to the indices of the gene mutations induced by the chemical mutagens) has been
      in the focus of attention. The conclusion has been made concerning impossibility
      to use pAins plasmid DNA in the diabetes mellitus gene therapy. It is necessary
      to test the mutagenic properties of the DNA molecules produced for gene therapy
      of human inherited diseases.

PMID- 8154051
TI  - [The ultrastructural characteristics of the changes in the rat liver in the
      dynamics of experimental endotoxemia].
AB  - Electron microscopic study was performed in the experiments on the rat liver
      while intravenously administering E. coli endotoxin. The dynamics of
      ultrastructural disorders during endotoxemia has been established and the role of
      "Kupffer cell-hepatocyte" microsystem in the liver detoxification function is
      shown.

PMID- 8154052
TI  - [Chromosomal anomalies in children with undifferentiated forms of metal
      retardation based on molecular cytogenetic research data].
AB  - The results of cytogenetic diagnosis of 1333 children with mental retardation and
      congenital malformations are presented. Chromosomal aberrations and chromosomal
      variants (1qh+, 9qh+, 16qh+) have been detected in 181 (13.9%) cases analyzed and
      in 158 (11.85%) cases, respectively. Molecular cytogenetic methods have been used
      for diagnosis or detalization of diagnosis in 42 cases from 181 (23.2%).
      Independent variation (or polymorphism) of copies number of "classical" and alpha
      satellite DNA sequences, forming pericentromeric regions (1qh+, 9qh+, 16qh+) has
      been detected in patients with chromosomal variants.

PMID- 8154053
TI  - [Thermal side effects after use of the pulsed IR laser on meniscus and bone
      tissue].
AB  - Thermal effects on meniscus and bone tissue after application of 314 boreholes
      using five different infrared (IR) lasers: Nd:YAG, Tm:YAG, Ho:YAG, Er:YAG,
      Cr,Er:YSGG (application energy 200 mJ, 400 mJ, 600 mJ, 800 mJ, 1000 mJ;
      repetition rate 2 Hz, 5 Hz; medium air, water rinse) were analyzed. The
      experimental set-up comprised for the beam guiding a focussing lens (f = 100 mm)
      or a flexible fiber (Ho:YAG). Damaged tissue was investigated macroscopically,
      histologically, and by scanning electron microscopy. Application in air caused
      carbonisation in all cases. Application in water showed thermal brown discoloring
      using Tm:YAG, Ho:YAG laser on meniscus tissue. The Nd:YAG did not ablate. The
      Er:YAG laser showed macroscopically precise boreholes without any discoloring of
      the adjacent tissue as well in meniscus as in bone. Cr:ErYSGG laser results were
      comparable with the results using an Er:YAG laser although ablation on bone
      tissue created higher thermal effects. For the aim of developing minimal invasive
      operating techniques the Er:YAG laser showed best results.

PMID- 8154054
TI  - [Limbus diagnosis by computerized tomography after initial traumatologic
      dislocation of the shoulder].
AB  - This paper shows a retrospective analysis of 98 shoulder joint CT scans after
      traumatic primary anterior dislocation in the period of 1988 till December 1991.
      The intraoperative findings and the X-ray characteristics beside arthrographic
      and MRI examinations led us to a classification of four types by pathomorphologic
      aspects, the type of the tear correlated to the degree of instability. For
      anterior limbus tear and lesions, a CT scan gives a diagnostic sensitivity of
      more than 90% (own rate 94.6%). Concerning our patients, the total lesions rate
      of 77.6% following first traumatic dislocation justifies a progressive
      examination and evaluation of the joint structures, that enhance further
      dislocations. Hereby, inspite of its invasivity, joint CT scan have, in
      comparison to other diagnostic procedures, proved to be routinely useful.

PMID- 8154055
TI  - [Ender nail with interlocking mechanism or dynamic hip screw in pertrochanteric
      fractures? A prospective study extending its limits].
AB  - In a prospective study on 148 patients with trochanteric fractures of the hip we
      compared the results of two implant-systems: the Ender-nailing modified by the
      dynamical interlocking method of Kempf and Bitar, and the dynamic hip screw (DHS)
      of the AO-ASIF. The Ender-method had the shorter operation time, earlier weight
      bearing and less septic complications. Fracture consolidation was complete after
      three months in all cases. But in 8% reosteosynthesis because of hip joint
      perforations of nails was necessary. The method leads in less cases to anatomical
      reduction (85%), more often relevant varus (9%) and rotationary (14%)
      malpositions and functional deficits in hip (25%) and knee joints (9%), compared
      with the DHS. The DHS had less implant complications, reosteosynthesis was
      necessary in 4%. Technical failures were seldom. In 96% anatomical reduction
      could be achieved and the function of the hip was in 87% good to excellent. The
      Ender-nailing with dynamic interlocking is a system for internal fixation of
      trochanteric fractures in elder patients. The DHS-system has better functional
      results. Both systems need to be performed in a very careful, exact surgical
      procedure, to avoid complications.

PMID- 8154056
TI  - [The clinical course of surgically managed para-articular femoral fractures in
      geriatric surgery].
AB  - 246 patients (average 82.4 years) with proximal femur fractures treated with
      bipolar endoprosthesis, sliding lag screw or Ender nailing, related to the
      fracture type were analysed in a retrospective study. Pre-existing diseases,
      duration of operation, postoperative complications, transfusions, hospital stay,
      mobility achieved and mortality were noted. In result we found a high
      multimorbidity related to the age, the highest requirement of transfusions in
      patients undergoing Ender nailing, a long period to achieve postoperative
      mobility, a long hospital stay and increasing mortality with average age and
      average hospital stay.

PMID- 8154057
TI  - [Long-term results of surgical management of patellar fractures. Conservative
      versus resection procedures].
AB  - In a retrospective analysis of 70 patellar fractures the-long-term results after
      surgery were followed-up for periods of up to twelve years. Subjectively,
      excellent or satisfactory results were reported by 89% (n = 62) of patients.
      Clinical evaluation in the Lysholm score showed excellent or good results in
      74.2% (n = 52) of cases. The results in the Lysholm score correlated well with
      the radiological evidence of arthrosis (p < 0.014) and with the clinical signs of
      chondropathy (p < 0.0005). Poor results (79.2 Lysholm points) were seen for
      comminuted fractures; however, the results for patients with distal transverse
      fractures were even lower (68.28 Lysholm points). Medial transverse fractures as
      well as distal patella pole ruptures were shown to have good prognostic results.
      In cases with comminuted fractures resection techniques are to be preferred to
      conservative procedures (p < 0.015). As regards long-term results in our patient
      population, partial patellectomy showed no obvious advantages over total
      patellectomy. In cases with multi-fragment fractures with questionable
      possibilities for reduction, cases with extensive cartilage damage as well as
      cases with distal transverse fractures partial or full patellectomy is
      recommended as the therapy of choice.

PMID- 8154058
TI  - [Lipofibroma of the median nerve. Clinical report of two cases].
AB  - The following article presents two new cases of a lipofibroma of the median
      nerve. This formation is a very rare benign tumor of peripheral nerve tissue. Up
      to now 30 cases have been reported in the literature and are reviewed in this
      article and are compared with the two cases reported. Besides the operative
      treatment, which made the neuropathological diagnosis possible, preoperative
      diagnosis has been extended by MNT-scans of the involved parts of the nerve. The
      noninfiltrating character of the tumor could be well recognized on these scans.
      The signal quality and the anatomical proximity to the median nerve made the
      diagnosis of a lipofibroma likely. By the postoperative histological reviews the
      diagnosis was confirmed in classic manner. The immunological marking of the S-100
      protein showed a remarkable reduction of this protein in these peripheral nerve
      tumors. The two cases reported by us recapitulate the clinical history typically
      and describe symptoms and our treatment for the lipofibroma of the median nerve.

PMID- 8154059
TI  - [Effectiveness of a support screw in condylar plate osteosynthesis of the
      proximal femur].
AB  - In some theoretical and clinical examinations a supporting screw in condylar and
      other angular plate osteosyntheses devices is proposed to increase the weight
      bearing capacity. We examined the weight bearing of a condylar plate with "U" and
      double "T" blade profile with and without supporting screw. The weight bearing
      capacity in the condylar plate with "U" profile was 450 +/- 350 N without and 550
      +/- 450 N with supporting screw. In the condylar plate groups with "double T"
      profile the weight bearing capacity was 1350 +/- 1250 N in the group without and
      1400 +/- 1300 N in the group with supporting screw. We concluded that the
      introduction of a supporting screw cannot improve significantly the weight
      bearing capacity of condylar plate osteosynthesis.

PMID- 8154060
TI  - [Risk information for patients in trauma surgery].

PMID- 8154061
TI  - Proceeding of the 45th annual meeting of the Scandinavian Neurosurgical Society.
      Uppsala, June 9-12, 1993. Abstracts.

PMID- 8154062
TI  - Transurethral collagen injection for urinary incontinence.

PMID- 8154063
TI  - Vaginal surgery for stress urinary incontinence.

PMID- 8154064
TI  - A 7.5/8.2 F actively deflectable, flexible ureteroscope: a new device for both
      diagnostic and therapeutic upper urinary tract endoscopy.
AB  - OBJECTIVE: To develop and employ in a prospective fashion a small-diameter,
      actively deflectable, flexible ureteroscope that could be easily placed into the
      upper urinary tract and would increase the overall therapeutic potential for this
      class of endoscope. METHODS: A small-diameter, actively deflectable flexible
      ureteroscope was recently employed in clinical trials at two university centers.
      Improvements in fiberoptic engineering allowed endoscope miniaturization (7.5 F
      tip and 8.2 F shaft) while maintaining a relatively large (3.6 F) centrally
      located working channel. A variety of design modifications were employed through
      various prototype stages. Mechanical parameters included maximizing two-way
      active deflection, adequate secondary deflection allowing access to the lower
      pole caliceal system, and maintaining a sturdy (nonbuckling) durometer. RESULTS:
      The 7.5 F flexible ureteroscope was employed in sixty-seven procedures (64
      patients). Therapeutic rather than purely diagnostic maneuvers made up the
      majority of procedures. Thirty-one upper ureteral, renal pelvic, or caliceal
      calculi were treated with a variety of endoscopic lithotriptors placed through
      the ureteroscope. Six patients underwent both biopsy and endoscopic treatment of
      superficial papillary transitional cell malignancies. Retrograde endopyelotomy,
      incision or dilation of ureteral strictures, extraction of renal pelvic foreign
      bodies, and endoscopic access and treatment of obstructed caliceal diverticula
      were other applications. Endoscopic access to the upper urinary tract rarely
      required active intramural ureteral dilation (14%). Excluding patients with prior
      ureteral stents or those who underwent rigid distal third ureteral endoscopy
      prior to flexible proximal ureteroscopy, 31 patients (48%) required no intramural
      ureteral dilation prior to placing the endoscope. CONCLUSIONS: The increased
      therapeutic potential observed with the 7.5 F actively deflectable, flexible
      ureteroscope opens a variety of upper urinary tract pathologic states to
      minimally invasive (endoscopic) treatments.

PMID- 8154065
TI  - Determination of indwelling ureteral stent patency: comparison of standard
      contrast and nuclear cystography, and lasix renography.
AB  - OBJECTIVE: Because of the difficulty in determining patency of Double-J ureteral
      catheters, a study was devised at Madigan Army Medical Center to determine the
      best method to demonstrate stented ureteral patency. METHODS: Forty-two patients
      requiring Double-J ureteral stenting for various clinical reasons were the study
      group. Outpatients underwent contrast retrograde cystography, nuclear
      cystography, and diuretic renography every four to six weeks during the stent
      duration or just prior to stent removal if the stents were indwelling for less
      than four weeks. In addition, four weeks after stent removal diuretic renography
      alone was done to evaluate for possible delayed obstructive effect of the
      ureteral stenting. RESULTS: A total of 53 stents and 42 patients were evaluated.
      Seventy-seven sets of studies were obtained. In only four instances did all three
      imaging methods agree on the obstruction. In the remaining 73 sets of data, at
      least one imaging technique indicated stented ureteral patency. The contrast
      retrograde cystogram was positive for reflux 52 times (71%). Nuclear cystography
      showed patency 54 times (74%) and an unobstructed diuretic renogram was obtained
      59 times (81%). In addition, five of the six diuretic renograms accomplished with
      patients in the supine position only and which showed obstruction were repeated
      with patients in the upright position, and they showed unobstructed function. The
      overall sensitivity for diuretic renography was 89 percent when the diuretic
      renogram was done with patients in the supine and upright positions. CONCLUSIONS:
      Diuretic renography is the most sensitive test for detecting stented ureteral
      patency. This test needs to be performed with patients in both the supine and
      upright positions.

PMID- 8154066
TI  - Retroperitoneoscopy: the Washington University Medical School experience.
AB  - OBJECTIVE: To describe our initial experience with balloon dilatation of the
      retroperitoneum. METHODS: In 12 patients undergoing laparoscopic renal surgery,
      the retroperitoneum was dilated using the technique of balloon dilatation. This
      technique is described and the operative procedure performed in each patient is
      outlined. The postoperative recovery data and complications are also presented.
      RESULTS: This procedure provided excellent exposure of the anatomic structures
      within the retroperitoneal space and simplified the surgical dissection by
      staying out of the abdominal cavity. CONCLUSIONS: Access to the retroperitoneal
      space is easily and quickly performed utilizing the technique of balloon dilation
      and may minimize the risk of injury to peritoneal organs.

PMID- 8154067
TI  - Renal effects of CO2 insufflation: oliguria and acute renal dysfunction in a rat
      pneumoperitoneum model.
AB  - OBJECTIVE: To determine the mechanism by which oliguria develops during raised
      intra-abdominal pressure secondary to CO2 insufflation, we created a rat
      pneumoperitoneum model. METHODS: Male Sprague-Dawley rats (n = 67) were organized
      into three groups. Each group was subjected to abdominal pressures of 0
      (control), 5, or 10 mm Hg, over one, two, and four hours. Fourteen additional
      rats underwent a two-hour period of 10 mm Hg insufflation pressure followed by
      desufflation to 0 mm Hg. Urine output (UO) and serum creatinine levels were
      measured both during insufflation at one, two, and four hours, and two, four,
      ten, and twenty-two hours following its release. These measurements were compared
      to control values at each time point. Ultrasonic flow probes placed around both
      the inferior vena cava (IVC) and abdominal aorta during insufflation
      characterized the effects of increased abdominal pressure on blood flow. The flow
      rate was determined at insufflation pressures of 0 (control, 100% flow) to 25 mm
      Hg. RESULTS: Rats subjected to 10 mm Hg pressure had significant decreases in UO
      (oliguria) compared to controls for up to four hours (P < 0.01). There were no
      significant differences in UO in the control or 5 mm Hg groups over each time
      interval. While a reduction in UO was observed at two, four, and ten hours
      postrelease, significance was achieved only at ten hours (P < 0.006). By twenty
      two hours postrelease, no differences in UO were observed. Serum creatinine
      elevations declined two hours postdesufflation. IVC flow was reduced by 92.9
      percent at 10 mm Hg, while arterial flow decreased by 46.4 percent. Flow was
      restored to preinsufflation levels after release of pneumoperitoneum.
      CONCLUSIONS: Oliguria can be produced in rats undergoing pneumoperitoneum. The
      renal effects of pneumoperitoneum are most likely related to renal vascular
      insufficiency from central venous compression.

PMID- 8154068
TI  - Receptivity of African-American men to prostate cancer screening.
AB  - OBJECTIVE: The lifetime risk of prostate cancer among African-American men is two
      times higher than that of white men. Mortality from the disease is almost three
      times greater in African-Americans than in whites. This study assesses the
      receptivity of older (fifty to seventy-four years of age) African-American men (n
      = 86) in Chicago to periodic (annual and semiannual) prostate cancer screening.
      METHODS: A telephone survey conducted in January and February 1993, was used to
      collect data on subject sociodemographic background and medical history and to
      gather information on knowledge, attitudes, and beliefs about prostate cancer and
      screening. Univariate and multivariate analyses were carried out to identify
      factors associated with subject receptivity to annual and semiannual screening.
      RESULTS: Logistic regression analyses revealed that receptivity to annual and
      semiannual (every six months) examination is strongly associated with the degree
      to which screening is perceived as a salient and coherent (i.e., important,
      effective, and convenient) preventive health behavior. An additional factor
      independently associated with willingness to go through semiannual screening was
      subjects' awareness that African-American men are at increased risk for prostate
      cancer compared to white men. CONCLUSIONS: Findings from this study suggest that
      African-American men are willing to undergo prostate screening and are more
      receptive to annual than semiannual screening. Participation in screening may be
      facilitated by the provision of health education messages that emphasize the
      salience and coherence of early detection and elevated population risk.

PMID- 8154069
TI  - Trends in treatment of localized prostate cancer by radical prostatectomy:
      observations from the Commission on Cancer National Cancer Database, 1985-1990.
AB  - OBJECTIVE: Tumor registry data were studied to assess the magnitude and nature of
      the trend toward increased use of radical prostatectomy for the treatment of
      newly diagnosed localized prostate cancer. METHODS: The Commission on Cancer of
      the American College of Surgeons National Cancer Data Base aggregates data from
      hospital tumor registries located throughout the United States. Data from this
      resource on 4,531 patients treated in 1985, 25,028 treated in 1988, and 21,697
      treated in 1990 were reviewed. RESULTS: The data indicate that selection of
      radical prostatectomy increased markedly over this interval. Use of radical
      prostatectomy was greatest in younger men in every year studied. The proportion
      of patients treated by radical prostatectomy was greatest in the western United
      States and least in New England and the mid-Atlantic region. Radical
      prostatectomy was associated with patients' socioeconomic status and race as well
      as with the hospital's caseload of patients with cancer. CONCLUSIONS: The pattern
      of care for localized prostate cancer is changing significantly. Further research
      is needed to assess whether these variations reflect differences in access to
      care or patterns of patient preference.

PMID- 8154071
TI  - Functional urethral closure with pubovaginal sling for destroyed female urethra
      after long-term urethral catheterization.
AB  - OBJECTIVE: To assess the pubovaginal sling as therapy for correction of the
      destroyed female urethra secondary to long-term indwelling Foley catheter
      management of neurogenic vesical dysfunction. METHODS: Fourteen women with
      neurologic disease and a patulous and nonfunctioning urethra underwent
      pubovaginal sling functional urethral closure. The purpose of the procedure is to
      achieve a dry perineum. Greater tension is applied to the sling suspension for
      urethral closure than is normally used to ensure continence for patients
      exhibiting intrinsic sphincter dysfunction without neurogenic vesical
      dysfunction. RESULTS: Two patients with adequate bladder capacity and compliance
      underwent only a pubovaginal sling suspension. They were subsequently managed
      with intermittent catheterization. In 5 patients, a sling operation in
      conjunction with enterocystoplasty was accomplished. In 5 patients, a sling
      procedure with an ileocystostomy and a cutaneous urostomy (bladder chimney) was
      utilized. In 2 patients, suprapubic tube drainage was established at the time of
      pubovaginal sling placement. All patients have achieved continence, without the
      need for absorbent pads, with follow-up time of six to sixty months (mean, 24
      months). Abdominal wall herniation has not developed in any patient. CONCLUSIONS:
      The pubovaginal sling cured incontinence and has resulted in a dry perineum with
      few problems. The sling procedure may be superior to transabdominal or
      transvaginal bladder neck closure without the risk of fistula formation.

PMID- 8154070
TI  - Combined laparoscopic pelvic lymph node dissection and modified belt radical
      perineal prostatectomy for localized prostatic adenocarcinoma.
AB  - OBJECTIVE: Despite many known advantages, the radical perineal prostatectomy
      (RPP) had fallen out of favor because of the need for a second incision for the
      regional lymph node dissection. Laparoscopic lymphadenectomy, however, provides
      an accurate and minimally invasive alternative to open lymph node dissection.
      Herein are reported the practical advantages of combining laparoscopic lymph node
      dissection (LPLND) with RPP. METHODS: Forty-nine patients with clinically
      localized carcinoma of the prostate were considered candidates for RPP using a
      modified Belt technique. Thirty-five patients underwent attempted LPLND and 31 of
      these patients subsequently underwent RPP; 14 patients underwent RPP alone.
      Variables examined included total operative time, transfusion requirement, length
      of hospital stay, continence, and potency. RESULTS: The mean operative time for
      LPLND combined with RPP in 31 patients, including time for repositioning, was 4.5
      hours (range 3.0 to 7.0 hours). Only 26 percent of the patients who underwent the
      combined approach required blood transfusions of which 75 percent received
      autologous units. Mean length of stay was six days, and laparoscopy did not
      contribute significantly to postoperative morbidity. Eighty-four percent of the
      patients are completely continent. Of 27 potent patients who underwent nerve
      sparing surgery, 22 percent are potent and an additional 30 percent are sexually
      active with intracavernous pharmacotherapy. There were no perioperative deaths, 2
      major complications, and 5 minor complications. CONCLUSIONS: Laparoscopic
      techniques now permit the urologist to utilize the perineal approach, and its
      many advantages, to radical prostatic extirpation without the need for a formal
      abdominal incision. The minimal blood loss and low morbidity associated with
      laparoscopic pelvic lymphadenectomy combined with the radical perineal
      prostatectomy make this procedure an attractive alternative to the open
      retropubic approach for clinically localized prostatic adenocarcinoma.

PMID- 8154072
TI  - Therapy and prognosis for male anterior urethral carcinoma: an update.
AB  - OBJECTIVE: The scarcity of reports evaluating the effect of current treatment
      strategies for male urethral carcinoma has prompted a review of our recent
      experience. Since our last report (1980), we have seen 23 patients with this
      disease. METHODS: We performed a retrospective chart review of 23 patients seen
      in our institution between 1979 and 1990 with this type of cancer. RESULTS: Fifty
      two percent of our patients are alive without evidence of disease, after a mean
      follow-up of fifty months (range, 5 to 156 months). Treatment analysis indicates
      that distal urethrectomy and partial penectomy are adequate in controlling local
      disease for tumors arising in the fossa navicularis and penile urethra,
      respectively, and that en bloc excision of the penis, scrotum, prostate, and
      bladder together with resection of the inferior pubic rami, using myocutaneous
      flaps to cover the surgical defect, can provide long-term disease-free survival
      for patients whose tumor originates in the bulbomembranous urethra. Use of
      cisplatin-based chemotherapy resulted in a prolonged survival for patients who
      presented with metastatic disease. CONCLUSIONS: We conclude that the prognosis
      for patients with urethral carcinoma has improved, and some of the patients are
      having a prolonged disease-free survival due, in part, to more effective local
      and regional control and improved chemotherapy.

PMID- 8154073
TI  - Chronic hematospermia: assessment by transrectal ultrasound.
AB  - OBJECTIVE: To evaluate transrectal ultrasound in the assessment of chronic
      hematospermia. METHODS: Twenty-six patients aged between twenty-five and seventy
      seven years (mean, 55.6 years) presenting with persistent hematospermia of an
      average duration of 10.2 months (range, 3 to 20 months) underwent transrectal
      ultrasound. Twenty-five asymptomatic men aged thirty-nine to eighty-two years
      (mean, 63 years) self-referred to our institution seeking transrectal ultrasound
      as a screening method for prostate cancer and with no previous history of
      hematospermia were used as controls. RESULTS: Significant sonographic findings
      not present in the control group were detected in 24 patients with hematospermia.
      These consisted of dilated seminal vesicles in 8, ejaculatory duct cysts in 4,
      ejaculatory or seminal vesicle calculi in 4, the presence of ejaculatory duct and
      seminal vesicle dilatation in 4, seminal vesicle cysts with ipsilateral renal
      agenesis and absence of the vas in 2, and an intraprostatic mullerian duct
      remnant in 2. Of the patients having biopsies, none was found to have malignancy.
      CONCLUSIONS: Transrectal ultrasound is the imaging modality of choice in the
      assessment of chronic hematospermia.

PMID- 8154074
TI  - Relationship between antisperm antibodies and testicular histologic changes in
      humans after vasectomy.
AB  - OBJECTIVE: To determine whether or not there is an association between testicular
      histologic changes and antisperm antibodies in vasectomized men. METHODS:
      Morphometry was performed on testicular biopsy specimens obtained from 19
      vasectomized men and 21 fertile control subjects. Antisperm antibody status was
      determined on the serum of each patient and control subject using the indirect
      immunobead assay. RESULTS: Significant increases in seminiferous tubule wall
      thickness (p < 0.001), focal interstitial fibrosis (p < 0.001), and percent
      composition of interstitium (p < 0.01) were observed in vasectomized men as
      compared with control subjects. Serum antisperm activity was present in 74
      percent of the vasectomized men but none in the control subjects (p < 0.001).
      There was no association between testicular histologic changes and immune status.
      CONCLUSIONS: Vasectomized men exhibit significant testicular histologic changes
      and increased autoimmune activity as compared with fertile control subjects.
      These histologic changes are not directly associated with antisperm antibody
      status, suggesting that some other pathophysiologic process must be responsible.

PMID- 8154075
TI  - Infection stones in children: a twenty-seven-year review.
AB  - OBJECTIVE: The objective of this study was to determine the relationship between
      urinary tract infection and pediatric urolithiasis and to characterize the
      pediatric infection stone former. METHODS: Two hundred seventy consecutive
      pediatric stone formers presenting over a twenty-seven-year period were studied.
      Of these, 161 children (60%) had infection-related stones. Account was taken of
      stone composition, anatomic location, associated anatomic lesions, and the rate
      of stone recurrence over a median follow-up of three years. RESULTS: The mean age
      of children with infection stones was 4.9 years, with two-thirds being under six
      years of age. Proteus mirabilis accounted for 82 percent of pure urine cultures.
      Seventy percent of stones were renal and 30 percent were ureteral or
      intravesical. One-third of patients had anatomic lesions (pelviureteric
      obstruction, primary obstructed megaureter, and others) contributing to stone
      formation. Recurrent stones occurred in 14 percent of cases. CONCLUSIONS: This
      study reaffirms the predominance of urinary tract infection secondary to P.
      mirabilis as the leading cause of pediatric urolithiasis in the United Kingdom.
      The significant recurrence rate suggests the importance of prophylactic
      antibiotics, surgical correction of congenital anomalies, and long-term follow-up
      of this patient population.

PMID- 8154076
TI  - Urinary N-acetyl-beta-glucosaminidase as a screening technique for vesicoureteral
      reflux.
AB  - OBJECTIVE: To determine if urinary N-acetyl-beta-glucosaminidase (NAG) assays
      could be applied as a screening test for early detection of vesicoureteral
      reflux. METHODS: Two hundred eighty-eight urine samples from children undergoing
      voiding cystourethrography (VCU) for a variety of urologic problems were assayed
      for N-acetyl-beta-glucosaminidase using spectrophotofluorimeter techniques.
      Sample creatinine levels were also determined using an auto analyzer. The urinary
      NAG to creatinine ratio for each patient was then compared to their VCU results,
      which were interpreted independently of the assay values and graded according to
      the International Reflux Classification system. The NAG to creatinine ratios were
      then classified according to their grade of reflux, and the mean NAG levels, plus
      one standard deviation, were calculated for each as well as for the nonrefluxing
      controls. Statistical analysis was done with P values obtained by Student's t
      test. RESULTS: A total of two hundred thirty-two specimens were evaluable with
      ninety (38.8%) samples collected from refluxing patients and one hundred forty
      two (61.2%) samples from nonrefluxers. The NAG levels standardized to urine
      creatinine revealed a mean value among refluxers of 15.514 mumol/g creatinine.
      This compared with a mean value of 14.611 mumol/g creatinine in the nonrefluxing
      group, with the difference being insignificant. When the mean NAG levels were
      compared for each grade of reflux to the nonrefluxing controls, only grade V had
      a significant elevation (44.561 mumol/g creatinine) above the nonrefluxers (P =
      0.0001). CONCLUSIONS: With the exception of grade V vesicoureteral reflux,
      urinary NAG levels do not reliably detect the presence of reflux and therefore
      cannot be accurately applied as a screening test for detection of this common
      urologic problem.

PMID- 8154077
TI  - Intravesical instillation of gentamicin sulfate: in vitro, rat, canine, and human
      studies.
AB  - OBJECTIVE: Intravesical instillation of gentamicin sulfate has been used
      empirically as prophylaxis and to treat bacilluria in spinal-cord-injured
      patients undergoing clean intermittent catheterization. To assess the risks of
      absorption and the effects of storage conditions on antimicrobial potency, a
      series of studies were conducted. METHODS: Four studies were carried out: (1) An
      infected fulgurated rat bladder model was created to determine the effects of
      inflammation and infection on absorption. (2) A canine model with bilateral
      vesicoureteral reflux and elevated bladder pressures (> 40 cmH2O) assessed the
      effects of reflux and storage pressure. (3) The effects in patients with
      associated conditions including renal transplantation, myelomeningocele,
      vesicoureteral reflux, and bladder augmentation, were analyzed. (4) To determine
      the effects of storage conditions, solutions of gentamicin sulfate (480 mg
      gentamicin sulfate in 1 L 0.9% NaCl) were made that controlled for pH, storage
      temperature, and duration. RESULTS: (1) Increased absorption was found in 43
      percent of rat serum samples. (2) None of the dogs demonstrated measurable
      absorption. (3) None of the patients likewise had measurable absorption. (4) All
      solutions were equally potent when tested against a panel of common urinary
      pathogens. Storage up to two months at room temperature without alkalinization
      had no effect on potency. CONCLUSIONS: Instilled intravesical gentamicin sulfate
      has a low risk of absorption and is highly effective. Severe bladder inflammation
      can increase transvesical absorption. It has prolonged stability without special
      storage conditions and should be considered as a route of prophylaxis in patients
      who perform intermittent catheterization.

PMID- 8154078
TI  - Gonadal tumors in disorders of sexual differentiation.
AB  - OBJECTIVE: To study the prevalence and distribution of gonadal tumors in patients
      with disorders of sexual differentiation. METHODS: Retrospective review of
      pathologic materials and clinical data on all patients diagnosed with mixed
      gonadal dysgenesis, pure gonadal dysgenesis, androgen insensitivity, and true
      hermaphroditism between 1982 and 1990. RESULTS: Twenty-one patients were
      identified and all underwent bilateral gonadectomy at the time of diagnosis. Nine
      of 21 patients had a gonadal tumor for a prevalence of 44 percent. Those at
      greatest risk for tumor were patients with mixed gonadal dysgenesis (6 of 11
      patients) and pure gonadal dysgenesis (2 of 3 patients). There were four
      gonadoblastomas, two dysgerminomas, and one each of teratocarcinoma, seminoma,
      cystadenofibroma, and juvenile granulosa cell tumor. CONCLUSIONS: The high
      prevalence of gonadal tumors in children with mixed and pure gonadal dysgenesis
      warrants consideration of early, bilateral, prophylactic gonadectomy once the
      diagnosis is established with certainty.

PMID- 8154079
TI  - Percutaneous renal biopsy utilizing ultrasonic guidance and a semiautomated
      device.
AB  - Percutaneous renal biopsy is a fundamental diagnostic technique in urology and
      nephrology, recently refined by real-time ultrasonic guidance. The technique
      described in this article is a biopsy method employing real-time ultrasonic
      guidance and a semiautomated device. The new device has been constructed to
      improve percutaneous biopsy technique and to obtain more perfect specimens. This
      technique was successfully performed in 20 patients undergoing renal biopsy.
      Diagnostically satisfactory material containing an average of ten glomeruli per
      specimen was obtained. The results obtained with the new device Biopty Bard have
      been compared with the results obtained from the same number of biopsies
      performed with the traditional technique.

PMID- 8154080
TI  - Entrapped stone basket managed by extracorporeal shock wave lithotripsy.

PMID- 8154081
TI  - Endourologic management of obstructed hydrocalyx after blunt renal trauma.
AB  - Significant renal injuries caused by blunt trauma can produce early and delayed
      complications. We report a case of blunt trauma that resulted in what appeared to
      be a persistent encapsulated hematoma, but was in reality an obstructed
      hydrocalyx. Communication with the collecting system was re-established
      percutaneously by a method similar to that used in the management of caliceal
      diverticula.

PMID- 8154082
TI  - Multilocular renal cyst (cystic nephroma) with mullerian-like stroma.
AB  - Multilocular renal cyst is an uncommon lesion of controversial histogenesis. The
      authors report a case of renal multilocular cyst with mullerian (ovarian)-like
      stroma. We suggest that this finding would support a dysontogenetic origin for
      the lesion.

PMID- 8154083
TI  - Spontaneous rupture of renal allograft.
AB  - Spontaneous rupture of a renal allograft was encountered in 3 male patients among
      75 consecutive renal transplants over a three-year period. In 1 patient, the
      transplant was from a living related donor, while the other two were cadaveric
      kidneys from pediatric donors. In 2 patients, allograft rupture followed steroid
      resistant rejection, while in the third with cadaveric kidney transplant, the
      rupture was associated with renal vein thrombosis. Two patients presented with
      classic symptoms of renal allograft rupture: sudden onset of severe pain and
      swelling over the allograft and hypotension, while in the third the rupture was
      found during exploration of the allograft with clinical diagnosis of renal artery
      thrombosis. Transplant nephrectomy was done in 2 patients, while successful
      surgical repair was performed in the third patient with living related
      transplant.

PMID- 8154084
TI  - Bowel injury in open technique laparoscopic cannula placement.
AB  - Open trocar placement is used by many surgeons during laparoscopy to avoid some
      of the potential complications of Veress needle and sharp trocar insertion. We
      describe a case of serosal bowel injury with a holding stitch placed to obtain an
      airtight peritoneal cavity during open laparoscopic trocar placement in a two
      year-old patient. The importance of inspection of the initial umbilical puncture
      site is emphasized and a rapid, simple technique for repair of minor bowel
      injuries is described.

PMID- 8154085
TI  - Spermatic cord metastasis from transitional cell carcinoma of the bladder.
AB  - A case of transitional cell carcinoma of the bladder metastasizing to the
      spermatic cord is reported. This represents the only clinically recognized site
      of tumor recurrence in a man treated with radical cystoprostatectomy followed by
      four cycles of adjuvant cis-platinum/methotrexate/vinblastine (CMV) chemotherapy
      for Stage D1 disease (local pelvic lymph node involvement). The existing
      literature concerning metastatic tumors of the spermatic cord is reviewed.

PMID- 8154086
TI  - Primary skeletal metastasis of a nonseminomatous germ cell tumor.
AB  - Bony metastasis is common in patients with germ cell tumor of the testicle;
      however, it is usually seen late in the disease process and is associated with
      lymph node or other visceral involvement. We present a case of isolated bony
      metastasis in a patient with a nonseminomatous germ cell tumor of the testis and
      normal retroperitoneal lymph nodes as determined by surgical resection.

PMID- 8154087
TI  - The renin-angiotensin system: revised concepts and implications for renal
      function.

PMID- 8154088
TI  - [Acid-base profile evaluation in central and peripheral arterial and venous blood
      in cattle].
AB  - In veterinary medicine mainly venous blood is used for acid-base balance
      determinations. This blood, however, does not allow to evaluate the respiratory
      component, therefore arterial blood samples have to be taken and examined in
      cases requiring such measurements (respiratory tract diseases, assessment of the
      degree of compensation in disturbed acid-base conditions). For this reason,
      central and peripheral arterial blood samples from the a. axillaris and a.
      subclavia, and the a. auricularis, respectively, were taken from 14 head of
      cattle, and the values of selected acid-base parameters (pH, pCO2, pO2, HCO3, BE
      and SAT) were compared. Simultaneously, venous blood samples (v. jugularis) were
      also examined. Comparison of arterial and venous blood samples (Tab. I) revealed
      statistically significant differences in pH (p < 0.01) as well as in pCO2, pO2
      and SAT values (p < 0.001). In HCO3 and BE, no significant differences were
      observed. Comparison of arterial blood samples in relation to sampling sites
      (peripheral and central) disclosed no significant differences in the single
      parameters; all values correlated at a high level (Tab. II, Figs. 1-6). The
      highest correlation levels were determined for BE (r = 0.984), HCO3 (r = 0.959),
      pH (r = 0.944) and pCO2 (r = 0.938) whereas those recorded for SAT (r = 0.877)
      and pO2 (r = 0.874) were lower. Arterial blood sampling from the a. auricularis
      caudalis seems to be simpler than sampling from the more central parts that are
      difficult to approach mainly in fat animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154089
TI  - [The effect of cadmium on the protozoan population and rumen fermentation of feed
      in an artificial rumen].
AB  - In our experiment, the effects of 5, 10 and 20 mg cadmium per kg dry matter (DM)
      on protozoan population and rumen fermentation of feed ration consisting of 11.7
      g DM of hay and 2.8 g DM of barley (80: 20%) were followed in artificial rumen
      (Rusitec). The results of the experiment showed that the addition of 5 and 10 mg
      cadmium per kg DM less significantly (P < 0.05) decreased the digestibility of
      DM, organic matter and neutral detergent fibre and significantly (P < 0.01)
      decreased the digestibility of cellulose of feed ration. It is interesting that
      the addition of 20 mg cadmium per kg DM did not influence these parameters.
      Although the total gas production showed a tendency of decrease due to the
      influence of the addition of 5, 10 and 20 mg cadmium/kg DM, methane and CO2
      production was not altered. However, cadmium significantly influenced the
      production of individual volatile fatty acids-VFA's (mmol/day). The addition of
      5, 10 and 20 mg cadmium per kg DM significantly increased acetic acid production
      (by 10-20%) and decreased propionic acid production (by 18-30%). Therefore, the
      acetate: propionate ratio was significantly increased (from 1.57 to 2.45-2.60) by
      the addition of cadmium. The production of n-valeric and iso-valeric acids was
      also significantly decreased in comparison with the control. The decrease of
      individual VFA's was more significant at the higher amount of cadmium added into
      the fermentation system. The proportions of individual VFA's in total VFA
      production expressed in molar % showed a similar character. The changes in the
      production of individual VFA's due to the influence of the addition of 5, 10 and
      20 mg cadmium per kg DM caused a decrease in energetic efficiency of VFA's (P <
      0.001) in comparison with the control. The other parameters of rumen fermentation
      - utilization of glucose, adenosine triphosphate (ATP) production, fermented
      hexose, fermented amino acids and fermented organic matter (OMF) were not
      influenced by the cadmium addition. Although the total microbial matter
      production in effluent and undigested feed (residues) was significantly (P <
      0.001) decreased by the addition of 5, 10 and 20 mg cadmium per kg DM, the
      efficiency of microbial synthesis expressed as YATP and g microbial N/kg OMF was
      not changed and achieved the values 11.78-12.68 (YATP), 25.56-28.35 (g microbial
      N/kg OMF), respectively. The total protozoan population was significantly
      decreased by the cadmium addition mainly as a result of the decrease of infusoria
      of Entodinium spp.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8154090
TI  - [Anesthesia in poultry].
AB  - Ketamine and ketamine-xylazine anesthesia was performed in the domestic fowl of
      the laying hybrid Hisex Brown and in Japanese quail (Coturnix coturnix) to test
      short-time anesthesia for the purposes of small surgical interventions. The
      findings of the authors Heidenreich and Wissdorf (1978) obtained in birds in the
      Zoo Park in Hannover were used to determine anesthetic doses and to assess the
      course of anesthesia, as well as a comparative study written by Samour et al.
      (1984) dealing with the use of some anesthetics in birds in the Zoo parks of
      Great Britain. The used anesthetics were ketamine in specialty Narkamon 5%
      (Leciva, a.s.) or a ketamine-xylazine mixture in specialty Rometar 2% (Leciva, a.
      s.). Both anesthetics were injected i.m. to breast muscle. Ataxia was observed
      after administration of ketamine only at doses of 20 and 30 mg/kg, the hens sat
      down and laid down on the side with stiff outstretched legs, they clapped the
      wings and tossed about in the cage. Immobilization was observed in Japanese
      quail, with sporadic incidence of excitations after administration of ketamine
      alone at a dose of 20 mg/kg live weight. A mixture of ketamine at a dose of 20
      mg/kg live weight and xylazine at a dose of 2-3 mg/kg live weight seems to be the
      best for the purposes of short-time anesthesia when good sedative, analgetic and
      myorelaxation effects are to be achieved in the domestic fowl and Japanese quail.

PMID- 8154091
TI  - [Secondary hyperparathyroidism in dogs].
AB  - Secondary hyperparathyroidism was found in 20 dogs over the period of 4.5 years;
      this represents 0.15% of the total number of examined animals. In all cases the
      dogs of large breeds suffered from this disease, Great Danes prevailed (nine
      dogs). The animals of the male sex fell ill thirteen times, the bitches seven
      times. The age of diseased dogs was from 3.5 to 20 months, dogs four to six
      months old prevailed (Tab. I). The disease was diagnosed on the basis of clinical
      examination, X-ray finding and biochemical analysis of blood plasma. The clinical
      picture was dominated by abnormal postures (95%), localized limping (90%),
      refusal to move (80%) and periosteal pain (65%). An X-ray findings showed reduced
      radiodensity of the skeleton (94%), weakening the wall of long bones (71%), bowed
      bend of the forearm (60%) and fractures (fissures) of long bones, or pelvis and
      vertebrae (59%). The results of blood plasma examination: calcium to phosphorus
      ratio 1:1 and higher (89%), ALP activity higher than 3 mukat/1 (72%), inorganic
      phosphorus concentration higher than 2.5 mmol/l and calcium concentration lower
      than 2.5 mmol/l (Tab. II). The diagnosis of secondary nutritional
      hyperparathyroidism was determined on the basis of anamnestic data, results of
      clinical and X-ray examination and blood plasma analyses. The analysis of blood
      plasma also revealed marked azotemia in four patients, while urine examination
      (proteinuria, hematuria, cylindruria) demonstrated simultaneous affection of the
      kidneys. Finally, it can be stated that these were all the cases of secondary
      nutritional hyperparathyroidism, which was complicated by renal
      hyperparathyroidism in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154092
TI  - Characteristics of strains of Staphylococcus aureus isolated at dairy farms.
AB  - Biochemical characteristics of 432 strains of S. aureus with special regard to
      those relevant to identification and estimation of enterotoxigenicity were
      examined. The STAPHYtest identified reliably 100, 100, 99 and 94% of strains
      isolated from milking machines, human carriers and bulk milk and quarter milk
      samples, respectively. Enterotoxins were produced by 9 strains from human
      carriers and only by 2, 1 and 1 strains isolated from bulk milk, milking machine
      and a quarter milk sample, respectively. 7, 4, 1 and 1 strains produced
      enterotoxins C, A, B and A + B, respectively. Enterotoxigenicity correlated well
      with the following characteristics: pigment production, presence of the clumping
      factor, coagulation of rabbit plasma, haemolysis of sheep erythrocytes,
      positivity in the STAPHYtest, fermentation of mannitol, strong haemolysis of
      bovine blood and strong thermonuclease activity. A simple three-step scheme for
      the examination of S. aureus isolates has been devised.

PMID- 8154094
TI  - Effective dose in cattle of toxic alkaloids from tall larkspur (Delphinium
      barbeyi).
AB  - We determined the po toxicity of tall larkspur (Delphinium barbeyi) of known
      alkaloid composition to cattle. We calculated the effective dose at which the
      alkaloids methyllycaconitine and 14-deacetylnudicauline, collectively termed
      total toxic alkaloid, caused collapse and sternal recumbency. The effective dose
      of total toxic alkaloid that produced sternal recumbency in steers was 11.2 mg/kg
      bw. Based on this dose, we hypothesize that the LD50 for a po dose of total toxic
      alkaloids in cattle will be 25 to 40 mg/kg bw.

PMID- 8154093
TI  - The effect of a single oral dose of tri-o-cresyl phosphate on neurotoxic esterase
      and acetylcholinesterase activities in the central nervous system, erythrocytes
      and plasma.
AB  - This study reports the activity of neurotoxic esterase (NTE) and
      acetylcholinesterase (AChE) in the blood and central nervous system (CNS) of
      swine 6, 12, 24 and 48 h after a single oral dose of 800 mg tri-o-cresyl
      phosphate (TOCP)/kg. At all evaluated intervals, inhibition of NTE activity in
      leukocytes and the CNS was 88% or higher, with only slight differences in NTE
      inhibition apparent among the various tissues examined. This extreme inhibition
      of NTE activity precluded correlation between inhibition of NTE in peripheral
      leukocytes and the CNS. However, the similarity in NTE response in leukocytes and
      the CNS following TOCP administration indicates the potential for leukocyte NTE
      as a biochemical marker for organophosphorus ester-induced delayed neurotoxicity
      (OPIDN) development. As the distribution pattern of NTE in the CNS of swine
      closely parallels that of man, these results further suggest that swine may prove
      a useful animal model for the study of OPIDN. The activity of AChE was highly
      variable based on time of assay and tissue examined. In general, plasma AChE
      activity was more severely depressed in all animals and responded more rapidly to
      TOCP administration. However, erythrocyte AChE more accurately reflected the
      enzyme's activity in the CNS and the clinical response to TOCP. Based on the data
      provided by this study, a threshold inhibition of erythrocyte AChE between 59 and
      74% is required for production of acute cholinergic signs.

PMID- 8154095
TI  - Pro and anticonvulsant effects of xylazine on convulsion models in rodents.
AB  - Pretreatment of mice with 30 mg xylazine/kg ip protected against convulsions
      induced by amphetamine, but it intensified pentylenetetrazole- and strychnine
      induced seizures. Xylazine pretreatment also protected rats against electroshock
      induced convulsions. These findings support a noradrenergic mechanism being
      involved in the proconvulsant and/or anticonvulsant effects of xylazine.

PMID- 8154096
TI  - Nifedipine in rat liver cirrhosis.
AB  - Rat liver cirrhosis induced by CCl4+ethanol was employed to assess the
      effectiveness of nifedipine in reducing liver injury. Nifedipine reduced the
      severity of hepatocellular necrosis, significantly decreased Mallory bodies (p <
      0.01), decreased polymorphonuclear inflammatory infiltrate (p < 0.05) and reduced
      perivenular fibrosis. Plasma lactic acid levels were significantly increased in
      the CCl4+ethanol group (p < 0.01). Lactacidaemia remained at normal values when
      the calcium antagonist blocker was employed. Nifedipine did not significantly
      alter the incidence of cirrhosis in this experimental model.

PMID- 8154098
TI  - Lead poisoning in small companion animals: an update (1987-1992).
AB  - Eighty-five cases of lead poisoning in small companion animals were
      retrospectively studied. Records from a lead toxicosis monitoring program at
      Angell Memorial Animal Hospital, Boston MA were reviewed from 1987 through 1992.
      The number of cases of lead poisoning substantially declined from the previous 6
      y. Affected animals included 53 dogs, 20 birds, 8 cats, 3 rabbits and 1 iguana.
      Ages ranged from 0.3-48 y, with a median age of 1.5 y. Gastrointestinal and
      neurologic signs predominated. Blood lead concentrations ranged from 40-620
      micrograms/dl. Seventy-three animals were successfully treated with chelation
      therapy; 7 animals required repeated treatments. Paint was identified as the most
      common source (32.4%) of lead exposure. Seventy of the 85 affected animals
      originated from the greater Boston area. Fifty-seven percent of the cases located
      within the Boston city limits could be traced to 3 inner city neighborhoods.

PMID- 8154097
TI  - Delayed and severe toxicities of a herbicide containing glufosinate and a
      surfactant.
AB  - We report a case of a 59-y-old woman who ingested a herbicide containing
      glufosinate. Though suffering from severe toxicity of this herbicide, she did not
      develop convulsions, which experimentally occurs in rats treated with
      glufosinate. The mechanisms of convulsions are not clear. Several clinical
      findings in poisoning by this herbicide are suspected to be caused by the
      surfactant components.

PMID- 8154099
TI  - The poisonous plant Oxalis cernua.

PMID- 8154100
TI  - Consideration of sheep as a minor species: comparison of drug metabolism and
      disposition with other domestic ruminants.

PMID- 8154101
TI  - Intoxication due to Nerium oleander in geese.

PMID- 8154102
TI  - Plants reported to be poisonous to animals in the United States.

PMID- 8154103
TI  - Developmental toxicity in hamsters of an aqueous extract of Fusarium moniliforme
      culture material containing known quantities of fumonisin B1.
AB  - The purpose of this study was to investigate potential detrimental effects of
      fumonisin B1 on the developing hamster. In experiments 1 and 2, timed-bred
      hamsters were dosed with 0.0 to 12.0 mg fumonisin B1/kg from day 8 to day 10 or
      day 12 of gestation. Clinical signs of material toxicity were not observed.
      Pregnant animals had reduced weight gains and lower total bilirubin levels than
      nonpregnant females. Hamsters were euthanized on day 15 of gestation. Histologic
      evaluation revealed autolytic placental changes expected in terminal gestation,
      as well as more advanced placental necrosis in association with fetal
      resorptions. Mean fetal weights and crown-rump lengths of living term fetuses on
      a per-litter basis did not differ between untreated controls and treated animals
      given 6.0 mg fumonisin B1/kg or less. However, at higher doses of fumonisin B1,
      there was an increased incidence of prenatal losses (deaths and resorptions). A
      greater percentage of litters had 1 or more fetuses affected, and a greater
      percentage of total fetuses were lost/litter as the fumonisin dosage increased.
      At 12.0 mg/kg, all litters were affected and 100% of the fetuses were dead and
      resorbing. Fumonisin B1 appears a developmental toxicant in hamsters. Toxicity is
      manifest by increased numbers of prenatal deaths and resorptions at doses that do
      not induce clinicopathologic evidence of maternal toxicity.

PMID- 8154104
TI  - Recent increases in numbers and risk of fatalities in young children ingesting
      iron preparations.
AB  - Iron preparations are the most frequent cause of pediatric ingestion fatalities.
      The purpose of this study was to quantify the impression of an increase in iron
      deaths in young children and to postulate on the reasons. Using the data provided
      by the American Association of Poison Control Centers, overall annual mortality
      rate from iron preparations and among children < 6 y was calculated and changes
      in incidence were recorded. Between 1983 and 1991, there was a 2 to 3-fold
      increase in the numbers of reported ingestions of iron preparations by toddlers.
      In the general population the annual mortality rate/100 exposures to iron
      preparations increased from 0.05 during 1983-1990 to 0.116 in 1991 (p < 0.01). A
      similar trend was noted in children < 6 y with a rate of 0.004 in 1983-1990
      compared with 0.12 in 1991 (p < 0.01). Hence, the increase in mortality was
      beyond what would be predicted from the increased number of ingestions noted. It
      is likely that increased awareness of pregnancy-induced anemia results in
      abundant use of iron pills. These pills have the appearance of candies, which
      should be changed immediately by legislation. During this period, the volume of
      iron preparations prescribed increased only marginally (16%), suggesting that
      over-the-counter use of iron pills increased substantially. In addition to
      warning labels and child-resistant packaging, an aggressive educational plan
      directed at the general population and physicians should be instituted
      immediately.

PMID- 8154105
TI  - The effect of highly diluted agitated thyroxine on the climbing activity of
      frogs.
AB  - We studied the influence of specially prepared highly diluted thyroxine on the
      spontaneous tendency of juvenile frogs, which were at the end of thyroxine
      controlled metamorphosis, to leave the water and climb onto land. The test
      dilution with a thyroxine concentration beyond Avogadro's value (dilution
      thyroxine D30) and the reference (dilution water D30) were prepared according to
      directions from the literature on homeopathy. A few drops of these solutions were
      added to tap water of basins containing the frogs. The frogs' climbing activities
      were monitored immediately after adding the solutions. The hypothesis derived
      from a preliminary study was that there is less climbing activity in frogs
      treated with dilution thyroxine D30 than in a reference group. This hypothesis
      was proven. Climbing activity diminished under the influence of dilution
      thyroxine D30, with statistical significance both in comparison to the effect of
      the analogously prepared solvent (dilution water D30) as well as in comparison to
      control observations before the start of treatment. When in a later step of
      observation the dilution water D30-control group was treated with dilution
      thyroxine D30, the diminishing effect on activity also occurred.

PMID- 8154106
TI  - The cost of employee turnover to a regional poison information center.
AB  - The quality and effectiveness of a regional poison information center (RPIC) are
      directly related to the skills and experience of the professional staff of
      specialists in poison information and to having the appropriate number of
      individuals in order to accurately and concisely respond to the thousands of
      telephone calls concerning acute/chronic poisoning emergencies. Since RPICs are
      traditionally small departments, the loss of even 1 key staff member can cause
      devastating results. A realistic appraisal of the actual costs associated with
      employee turnover was done at our RPIC and considered the following items:
      Advertising and recruiting expenses; interviewing expenses; processing costs;
      orientation and training expenses; and overtime costs including fringe benefits
      and premium shift differentials. The over-all tangible costs related to turnover
      of an individual who is certified or qualified to be certified as a specialist in
      poison information is approximately $17,486. The specific cost categories
      included advertising/recruiting, $326; interviewing expenses, $360; orientation
      and training, $9,250; processing, $350; overtime monies, $7,200. The less
      tangible effects of turnover cannot be strictly measured in dollars, but can be
      reflected in reduced quality assurance factors, increased sick time, and
      decreased morale. While staff salaries and benefits usually account for 75% to
      85% of a RPIC's operating budget, and since external sources of revenue do not
      offset the operational expenses, it is becoming increasingly difficult to remain
      competitive in today's current professional salary climate. While the loss of
      talent and its cumulative effect on quality is impossible to quantitatively
      measure, we have attempted to calculate the real financial burden associated with
      replacing personnel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154107
TI  - Activated charcoal delivery through small-bore tubing.

PMID- 8154108
TI  - Current estimates from the National Health Interview Survey, 1992.

PMID- 8154109
TI  - [The effect of a UHF electrical field applied bitemporally on parameters of the
      hemostatic system in patients with ischemic heart disease and II-degree
      atherosclerotic stenosis of the coronary arteries].

PMID- 8154110
TI  - [Effect of electromagnetic waves with 59-63 GHz frequency on myocardial infarct
      patients in the subacute stage].
AB  - Exposure to electromagnetic millimetric waves and placebo treatment were examined
      for their impact on myocardial performance, bioelectrical activity, and
      contractility, exercise tolerance, microcirculation, daily urinary hydroproline
      excretion in 166 patients with subacute myocardial infarction. Electromagnetic
      millimetric waves were demonstrated to exert a stimulating action on a reparative
      process in the myocardium.

PMID- 8154111
TI  - [Combined use of disaggregants and galvanic current in cerebrocardio-vascular
      pathology].
AB  - The efficiency of combined use of the disaggregant aspirin and electroplate
      current on the precordial area was studied in 230 patients with coronary heart
      disease concurrent with cerebral disorders. The procedure was shown to have a
      positive action on the time course of clinical symptoms, the status of central
      hemodynamics, physical fitness, and psychoemotional status of the patients.

PMID- 8154112
TI  - [Effect of oxygen baths on lipid peroxidation processes in patients with
      circulatory encephalopathy].

PMID- 8154113
TI  - [Combined therapy of duodenal ulcer associated with Helicobacter pylori with
      electromagnetic decimeter waves and colloidal bismuth subcitrate].

PMID- 8154114
TI  - [Pelotherapy in chronic pancreatitis].

PMID- 8154115
TI  - [Effect of health resort treatment on the status of the oxidant and antioxidant
      systems in women with disordered reproductive function residing in the area of
      the Chernobyl Atomic Power Plant accident].
AB  - Lipid peroxidation system and its reaction to balneotherapy (hydrogen sulfide and
      iodine bromide exposure) were examined in 60 women with reproductive system
      disorders living in radionuclide pollution zone after the Chernobyl accident.
      Certain specificities of lipid peroxidation system in this patient population
      were detected and a favorable effect of the said balneotherapy noted.

PMID- 8154116
TI  - [The use of the Shirsal concentrate in treating chronic inflammatory diseases of
      the uterine adnexa].
AB  - Shirsal concentrate, mineral water salt from Shira lake, of sulfate chloride
      magnesium and sodium composition is suggested for therapy of women suffering from
      chronic inflammations of pelvic organs. Eighty-three women were administered
      Shirsal solution electrophoresis combined with endovaginal vibration massage or
      microenemas of 0.5% solution of the same agent. The treatment had an evident anti
      inflammatory, analgesic, and resolving effect.

PMID- 8154117
TI  - [Perspectives for developing the mineral water base of Udmurtia].

PMID- 8154118
TI  - [The use of polyhexamethyleneguanidine-based bactericidal coatings in balneologic
      equipment systems].

PMID- 8154119
TI  - [Submersion vibration traction in treating patients with neurologic
      manifestations of lumbar osteochondrosis].

PMID- 8154120
TI  - [The blood antioxidant system in patients with ischemic heart disease undergoing
      laser therapy].
AB  - Catalyse activity and lipid peroxidation were studied in the sera of patients
      with coronary heart disease who had been exposed to red and infrared low-energy
      laser radiation (LLR) applied to the skin projections of the heart and its
      reflexogenic areas. It was found that the optimal normalizing effect occurred
      with the red band of LLR applied in the rehabilitative period to patients with
      prior myocardial infarction concurrent with hypertensive disease and stable
      angina of functional classes I and II. In functional class III stable angina,
      infrared LLR had advantages over the red on when they acted on the blood
      antioxidative system.

PMID- 8154121
TI  - [Interference currents--an alternative to uterotonic drugs after cesarean
      section].

PMID- 8154122
TI  - [Medical weather predicting--a very important scientific branch of modern
      meteoropathology].

PMID- 8154123
TI  - [Morbidity with chronic forms of pathology in children from areas contaminated by
      radionuclides].

PMID- 8154124
TI  - [Experience with clinical trial of physiotherapeutic equipment in the obstetrical
      and gynecological clinic].

PMID- 8154125
TI  - [Lumbar pains and physical therapy methods].

PMID- 8154126
TI  - [Significance of phytocides in environmental hygiene].

PMID- 8154127
TI  - [Current problems of experimental physiotherapy].

PMID- 8154128
TI  - [The rebirth of a health resort].

PMID- 8154129
TI  - [Effect of transthoracic galvanization on the nature and incidence of
      complications at the hospital stage of treating patients with acute myocardial
      infarct].
AB  - The impact of transcardiac galvanization on the pattern and incidence of
      complications occurring in the hospital period was studied by using the data of
      examination of 110 patients with primary uncomplicated large anterior myocardial
      infarction who had been admitted to the hospital no later than 6 hours of the
      onset. ECG monitoring, echocardiography, X-ray graphy, echocardiography, and
      clinical study were used. It was found that a course of transthoracic
      galvanization in the multimodality therapy for acute myocardial infarction
      contributed to a more rapid relief of the pain syndrome, to a decrease in the
      incidence of cardiac rhythm and conduction disturbances, in relapses of
      myocardial infarction, left ventricular aneurysm, early postinfarction angina
      pectoris in the hospital period.

PMID- 8154130
TI  - [Heparin-induced extracorporeal LDL precipitation (HELP): a new therapeutic
      intervention in cerebrovascular diseases and peripheral arterial occlusive
      disease].
AB  - Coronary heart disease, stroke and peripheral arterial disease are the major
      causes for death and disability in industrialized countries. These diseases have
      a common cause: Their development is based on atherosclerotic changes of blood
      vessels, induced by risk factors such as elevated values of lipoproteins and
      fibrinogen. There is no doubt that the risk factors mentioned above are even
      related to a dramatically deterioration of the hemorheologic pattern, thus
      reducing perfusion. Due to this massage there are attempts to treat ischemia via
      hemorheological intervention. Although a number of different methods is available
      -hemodilution, defibrinogenation or oral medication--it was not possible to
      improve the hemorheologic pattern fast, safe, and efficient to date. A new
      treatment modality, utilizing the heparin-induced extracorporeal LDL
      precipitation (HELP), now offers the possibility to obtain therapeutical success
      not only in cases of severe hypercholesterolemia but even in the field of
      hemorheology: Using HELP a safe and rapid reduction of lipid fractions and
      fibrinogen has become feasible, thus providing an acute improvement of red cell
      aggregation and filterability of blood cells, whole blood and plasma viscosity
      and thereby of microcirculation. As it is known that cerebrovascular diseases are
      related to disturbances of the hemorheological situation, the HELP system is used
      at the Department of Neurology, Karl-Franzens University of Graz, for the
      treatment of acute stroke, cerebral multi-infarct disease but even in cases of
      peripheral arterial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154131
TI  - [Dante Alighieri and we neurosurgeons].
AB  - Accompanied by Dante and Vergil the author compares persons and events of the
      "Divine Comedy" with those concerning the Austrian neurosurgery in the last 50
      years. The burlesque description culminates in pointing out the wage rewarding
      the neurosurgeon at the end of the life for all troubles of his branch.

PMID- 8154132
TI  - [Danger to self and others as a prerequisite for psychiatric commitment].
AB  - The words of section 3 Z. 1 UbG (Law on commitment to a psychiatric hospital) are
      interpreted very restrictive meaning only physical injuries. An extensive
      interpretation concerning the danger of one's health would include also a
      psychical affect (for oneself or others). Neither section 3 Z. 1 UbG itself, nor
      the Law on protection of the personal freedom (Art. 2 Abs. 1 Z. 5 BVG, BGBl.
      1988/684) would contradict. But in that case the danger of the psychical wealth
      must be measured at the seriousness, importance and the principle of
      subsidiarity.

PMID- 8154134
TI  - [The first epileptic seizure. Diagnostic and therapeutic decisions].

PMID- 8154133
TI  - [Neuroborreliosis. Symptomatology--diagnosis--therapy].

PMID- 8154135
TI  - [Diagnosis and therapy of cerebral sinus and venous thrombosis].

PMID- 8154136
TI  - [The risk of substitution therapy with blood and blood products].

PMID- 8154137
TI  - [The kidney and hypertension].

PMID- 8154138
TI  - [Hematuria. Current diagnosis and differential diagnosis].

PMID- 8154139
TI  - [Eating abundant fruit and vegetables in prevention of cancer].

PMID- 8154140
TI  - [Does spotted typhus still exist? Imported tick bite fever--differential
      diagnosis of an exanthema with fever].

PMID- 8154141
TI  - [Differential diagnosis of tremor].

PMID- 8154142
TI  - [Manifestation of isolated heart metastasis in follicular thyroid cancer (case
      report)].

PMID- 8154143
TI  - [Paroxysmal nocturnal hemoglobinuria. Differentiation from other acquired
      hemolytic anemias and confirming the diagnosis].

PMID- 8154144
TI  - [A case from general practice (15): New onset constipation in the elderly].

PMID- 8154145
TI  - [The status of Jews in Prussia in the 19th century and the Berlin Medical
      Faculty].

PMID- 8154146
TI  - [Experimental medicine--the contributions of Traube and Virchow].

PMID- 8154147
TI  - [Freedom and responsibility of the research physician].

PMID- 8154148
TI  - [Operation and angioplasty in cerebrovascular disorders].
AB  - Carotid endarterectomy until recently was performed to prevent the progression of
      a stenosis to an occlusion and hemodynamically induced strokes in patients with
      tight stenosis. Operation of ulcerated plaques or stenosis was supposed to
      prevent embolic stroke. The operation has no indication for a stenosis of the
      internal carotid artery (ICA) > 50% and < 90% in asymptomatic persons. Whether
      persons with an asymptomatic stenosis > 90% show a preventive effect of the
      operation is not known at this time. According to the Mayo-Clinic study, persons
      with asymptomatic ICA stenosis should be treated with aspirin to prevent
      myocardial infarction. Two large controlled trials have shown that endarterectomy
      can prevent stroke in patients with transient ischemic attacks (TIA) or minor
      stroke and an ICA-stenosis > 70%. This preventive effect is lost when the
      complication rate of the procedure is higher than 5% (mortality and morbidity).
      In patients with stenosis < 30% the operation has no preventive effect. Both
      studies continue to recruit patients with symptomatic stenoses between 30 and
      70%. Patients with severe neurological deficits or a large lesion in CT should
      not be operated as would be patients with an acute stroke. The extra-intracranial
      bypass operation did not prevent stroke in patients with an occlusion of the ICA
      or severe stenosis or occlusion of the middle cerebral artery. Angioplasty has
      been applied to dilate stenoses of the subclavian artery in patients with
      subclavian-steal syndrome and disabling vertebro-basilar TIA. Angioplasty in the
      carotid artery is still an experimental procedure, which should only be applied
      in controlled trials.

PMID- 8154149
TI  - [Operation and angioplasty in peripheral arterial occlusive disease].
AB  - The treatment of peripheral arterial occlusive disease is based on conservative
      treatment, surgical revascularization, and percutaneous transluminal catheter
      based methods. The differential indication for treatment is mainly influenced by
      clinical and angiographic parameters. The indications for surgical and catheter
      based revascularization are relatively clear: Short occlusions and stenoses of
      the iliac and femoropopliteal arteries in symptomatic patients are ideal
      indications for PTA. In patients with critical leg ischemia percutaneous
      revascularization techniques should always be considered to treat these patients
      with the minimal invasive approach. Long occlusions of iliac and femoral arteries
      and diffuse occlusions of multiple segments in patients with severe claudication,
      ischemic rest pain or gangrene are best treated by primary surgical
      revascularization. Beside the established percutaneous transluminal balloon
      angioplasty several new interventional techniques were developed to extend the
      indications for percutaneous treatment, improve acute success rates and reduce
      complications. Probably, also long-term results after catheter-based therapy of
      peripheral arterial occlusive disease may be improved by these new technologies.

PMID- 8154150
TI  - [New diagnostic methods--ultrasound and clinico-chemical procedures in diagnosis
      of ischemia].
AB  - Stress-echocardiography represents a new non-invasive, alternative approach in
      the assessment of patients with coronary artery disease. By means of dynamic or
      pharmacological stress or by atrial pacing regional wall motion abnormalities can
      be induced, which can be identified by 2D-echocardiography. Beyond the indirect
      detection of ischemia this approach allows a better quantification of the amount
      of ischemia and of global LV function, which is advantageous compared to stress
      ECG recording or myocardial scintigraphy. Disadvantageous is however, the
      subjective reading of the echo itself. In experienced hands stress
      echocardiography has proven to be as sensitive and specific as myocardial
      scintigraphy. Recently, in addition the diagnostic potential of myocardial cell
      injury has been improved by the detection of specific antibodies versus Troponin
      T. In comparison with conventional biochemical markers of myocardial cell
      necrosis Troponin T analysis has been proven to be superior in postoperative or
      traumatic cardiac damage or in the setting of acute myocardial infarction. In
      this situation the time window is improved by an earlier rise compared to CK and
      a longer detection rate compared to lactate dehydrogenase.

PMID- 8154152
TI  - [Organ ischemia].

PMID- 8154151
TI  - [New intervention procedures: lasers, atherectomy, stents].
AB  - New coronary devices--atherectomy, laser angioplasty, and stents--have been
      designed to overcome main limitations of conventional balloon angioplasty (PTCA).
      So far, none of the new devices has clearly demonstrated a general superiority
      regarding acute complications. Late outcome and restenosis are not affected by
      the type of intervention, but mainly determined by the primary success, i.e. the
      safely obtained postprocedure lumen diameter. Although the new coronary devices
      may not replace conventional PTCA in "standard" situations, there are specific
      indications (venous bypass grafts, aorto-ostial lesions, complex calcified
      lesions) for atherectomy, laser angioplasty, and stents with better acute results
      compared to PTCA. Since the best post-procedural result determines the extent of
      restenosis, it is crucial to select the appropriate device for special lesions or
      acute complications.

PMID- 8154153
TI  - [Interaction of blood and the vascular wall: hemostatic aspects].
AB  - The coagulation enzyme thrombin, a serine protease like all other coagulation
      factors, plays a central role in the hemostatic processes engaged after injurious
      events. It induces, with particular efficacy, the aggregation of blood platelets
      (primary hemostasis) and accounts, via splitting of fibrinogen to fibrin, for the
      event actually responsible for the coagulation of blood (secondary hemostasis).
      As is well-known, thrombin itself is generated by a cascade of activation events
      involving various coagulation factors (F). In this respect the "tissue factor"
      (TF, formerly known as thromboplastin), in combination with F VIIa, attains
      decisive significance, not only in the extrinsic pathway of coagulation
      (activation of F X-->Xa), but also in the intrinsic pathway (activation of F IX-
      >IXa). Under physiological circumstances, platelet aggregation and coagulation
      are restricted to the area of the vascular lesion, since the surrounding intact
      endothelium inhibits an intraluminal spreading of both processes. These
      "antithrombotic" features of the endothelium encompass antiaggregatory mechanisms
      (formation and release of prostacyclin [PGI2], adenosine, EDRF [NO], degradation
      of ADP and other nucleotides mediated by ecto-nucleotidases) as well as anti
      coagulatory properties (formation and release of "tissue factor pathway
      inhibitor" [TFPI], which blocks the coagulation cascade by joining F Xa, TF and F
      VIIa into an inactive complex, thrombomodulin--thrombin induced activation of
      protein C, which, together with protein S, inactivates F Va and F VIIIa, thereby
      attenuating further generation of thrombin, and the heparan sulfate-enhanced
      activation of antithrombin III and heparin-cofactor II).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8154154
TI  - [Chronic myocardial ischemia--hibernating myocardium: characteristics and
      limits].
AB  - Myocardial ischemia has traditionally been characterized as an imbalance between
      energy supply and demand. In the initial seconds after a sudden reduction of
      coronary blood flow, myocardial energy demand most certainly exceeds the reduced
      energy supply. This temporary mismatch, however, is an inherently unstable
      condition because regional contractile dysfunction ensues. The mechanisms
      responsible for the rapid reduction in contractile function of the acutely
      ischemic myocardium are still poorly understood. If some residual blood flow
      exists, a state of "perfusion-contraction matching" can be maintained, at least
      for several hours, without the development of irreversible damage. A situation of
      persistent contractile failure in viable myocardium with normalizes upon
      reperfusion has been termed myocardial "hibernation". The metabolic status of
      such hypoperfused myocardium improves over the first few hours as myocardial
      lactate production is attenuated and creatine phosphate, after an initial
      reduction, returns towards control values. The "hibernating" myocardium can
      respond to an inotropic stimulation by dobutamine with increased function. The
      recruitment of an inotropic reserve implies increased energy utilization. In
      fact, the partially normalized lactate production is again increased, and
      creatine phosphate is decreased again. Apparently the inotropic challenge once
      again precipitates a supply-demand imbalance which had been at least partially
      corrected by the ischemia-induced decrease of regional contractile function. This
      situation of an increased regional contractile function at the expense of
      metabolic recovery during inotropic stimulation can be used to identify
      "hibernating" myocardium. The development of such a delicate balance between
      energy supply and energy demand is easily disturbed by unfavorable alterations in
      the supply/demand ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154155
TI  - [The "stunned" and "hibernating myocardium"--diagnosis and clinical
      implications].
AB  - Myocardial stunning and myocardial hibernation gain increasing importance for the
      therapy of myocardial ischemia. It has been demonstrated that myocardial stunning
      may be reversible after successful reperfusion, although this may need weeks or
      even months. Similarly, noncontracting myocardial areas may regain contractile
      properties after successful dilatation of high grade stenoses or after bypass
      operation (myocardial hibernation). The diagnosis of myocardial stunning or
      myocardial hibernation usually is made by nuclear medicine (201Tl or 99Tc-MIBI).
      201Tl-Imaging after 24 hours or after reinjection seems to be the best method to
      prove myocardial hibernation. Dobutamine stress echocardiography may gain
      importance in the future.

PMID- 8154156
TI  - [Ventricular tachyarrhythmia in acute and chronic myocardial ischemia: value of
      diagnostic procedures].
AB  - The analysis of the outcome of patients after myocardial infarction in general,
      as well as of studies to predict the outcome of asymptomatic post-myocardial
      infarction patients by non-invasive methods, leads to the following conclusions:
      1) The incidence of ventricular fibrillation and mortality after acute myocardial
      infarction has been declining since the 1970s (2); the causes for this reduction
      are presumably multifactorial (thrombolysis of acute infarction, administration
      of ACE-inhibitors and increasing prescription of beta-blockers, improvement of
      intensive care medicine, rigorous correction of risk factors). 2) Development of
      ventricular tachycardia, electrocardiographically documented ventricular
      fibrillation or successful reanimation due to sudden circulatory arrest in
      clinical studies of post-myocardial infarction patients are endpoints which in
      future studies must be differentiated from each other. 3) In contrast to previous
      assumptions, the outcome of patients with primary ventricular fibrillation after
      acute myocardial infarction, that is, without preceding symptoms is guarded, so
      that such an event should prompt invasive diagnostic evaluation (coronary
      arteriography, programmed stimulation (?)). 4) Newer methods for risk
      stratification after myocardial infarction during the chronic phase, such as
      programmed stimulation, late potential analysis from the body surface as well as
      programmed ventricular stimulation appear to be superior to more conventional
      methods such as long-term ECG monitoring as well as exercise testing. It is
      recommended that all methods which determine the arrhythmogenic substrate are
      combined with a parameter of left ventricular ejection fraction because of the
      paramount importance of left ventricular pump function.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8154157
TI  - [Ventricular tachyarrhythmia. Drug therapy and evaluation of success].
AB  - In principle, all antiarrhythmic drugs (classes 1-3) are useful in the treatment
      of ventricular tachyarrhythmias. In special cases even Ca-antagonists (class 4)
      can be effective. Holter monitoring and programmed ventricular stimulation are
      clinical tools for predicting efficacy and controlling proarrhythmic effects.
      However, only in a limited number of patients are the prerequisites given for
      testing with one or the other method. Using long-term tape recording the
      suppression of ventricular salvoes by an antiarrhythmic drug seems to predict a
      good prognosis. In the electrophysiological lab complete or partial suppression
      of inducibility of the arrhythmias during programmed stimulation under
      antiarrhythmic treatment has a high predictive value as far as recurrence during
      follow-up is concerned. Using Holter criteria the efficacy of antiarrhythmic
      drugs is higher than with programmed stimulation. However, invasive
      electrophysiological testing has a higher sensitivity, i.e., a low rate of false
      positive results. As the results of two newer studies question the value of both
      methods, a definitive answer of the problem of optimal control of antiarrhythmic
      therapy cannot be given today.

PMID- 8154158
TI  - [Ventricular tachyarrhythmia in acute and chronic myocardial ischemia: non-drug
      therapy and evaluation of outcome].
AB  - In recent years new methods of non-pharmacological therapy of ventricular
      tachyarrhythmias have gained increasing importance. The development of
      implantable defibrillators and increasing experience with catheter ablation
      techniques represent important alternatives to pharmacological antiarrhythmic
      therapy which is presently employed only in a subgroup of patients with life
      threatening tachyarrhythmias and coronary heart disease.

PMID- 8154159
TI  - [Diagnosis of the dynamic lesion].
AB  - Rupture of atheromatous plaques, thrombosis and spastic contractions cause
      dynamic lesions in coronary arteries. This review focuses on the diagnostic
      approach to vasospastic lesions. Our current knowledge considers vasospastic
      angina as a--most likely--localized disease of the vascular smooth muscle, which
      occurs in nonatherosclerotic as well as in atherosclerotic segments. Currently
      the diagnosis can only be proven by functional tests under angiographical
      control. Since the pathophysiological mechanisms leading to vasospasm remain
      unclear, only empirically developed pharmacological tests are available. The use
      of ergonovine alkaloids is well established, the feasibility of acetylcholine is
      under investigation. The reproducibility regarding the course of the disease and
      the localization of the lesion has not yet been determined. The necessity to
      state the diagnosis is given by the improved prognosis of the disease under
      effective therapy with calcium channel blockers and nitrates.

PMID- 8154160
TI  - [Risk factors of arteriosclerosis. Differential profile--various mechanisms?].
AB  - Up to the present more than 250 factors have been discussed as being risk factors
      for arteriosclerosis. Yet only a very few pathogenetic mechanisms have actually
      been proven to be causative in maintaining or complicating the disease.
      Experimental research in atherosclerosis reflects on a history of approximately
      80 years, starting with the remarkable discovery by Windaus in 1912, who for the
      first time described that in atherosclerotic material 30 times more cholesterol
      is found as compared to healthy material. Today, due to an enormous quantity of
      experimental, biochemical, cellular and molecular biological data it is clear
      that the cholesterol of an atherosclerotic plaque is not being built at the
      location of deposit but rather derives from circulating plasmalipoproteins,
      especially from the LDL and IDL particles. Predisposition requires exceeding a
      threshold concentration of approximately 100 mg/dl cholesterol in plasma and its
      biological modification. In atherogenesis essentially five cell types are
      involved: the endothelium, the thrombocytes, the monocyte/macrophage system, the
      smooth muscle cells of the intima, and the T-lymphocytes. As a consequence of a
      rather complicated interaction of lipoproteins with these cells changes of the
      endothelium are initiated which eventually lead to lipid deposition. From early
      clusters, the so-called fatty streaks, and under unfavorable circumstances and
      unlimited growth atherosclerotic plaques may develop with the inherent danger of
      rupture and thrombotic occlusion. The vulnerability respectively the resistance
      of the arterial wall towards hypercholesterolemia is influenced by other so
      called primary risk factors such as hypertension, cigarette smoking, diabetes
      mellitus, and hyperfibrinogenemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154161
TI  - [Slowing the progression and regression of the basic arteriosclerotic process].
AB  - If patients with coronary artery disease are followed by "usual care" nearly half
      of them will experience significant progression of their disease within five
      years. Therefore, it is justified to develop interventions in order to retard the
      rate of progression and reduce the number of clinical events. In relevant studies
      published up to this date two different strategies were applied, first, reduction
      of risk factors by low fat diet, physical exercise, lipid lowering agents or
      partial ileal bypass; second, inhibition of atherogenesis by application of
      calcium blocking agents. The effect on progression of coronary artery disease was
      assessed by digital angiography in the majority of studies; without exception a
      positive effect was noted in all of them. In the calcium blocker studies this
      effect, however, was limited to new or minimal lesions. The magnitude of
      morphological difference between intervention and control groups ranged below 0.5
      mm and thus approached the long term variability of quantitative coronary
      angiography. The frequency of clinical events was reduced in only two studies,
      whereas they were increased in four intervention groups. CONCLUSIONS: Reduction
      of risk factors or application of calcium blockers are capable of retarding
      progression of coronary artery disease; predominant regression, however, seems to
      be unattainable. The frequency of clinical events is determined by additional
      factors other than morphologic changes.

PMID- 8154162
TI  - [Possible significance of free oxygen radicals for reperfusion injury].
AB  - Enhanced formation of radicals during post-ischemic reperfusion, foremost of
      superoxide (O2-) and hydroxyl (OH) radicals, has been directly and indirectly
      demonstrated in a number of tissues. However, the close chemical
      interrelationship of O2- and OH with other non-radical oxidants, such as hydrogen
      peroxide (H2O2) and hypochlorous acid (HOCl), makes it prudent to speak of
      reactive oxygen metabolites in conjunction with cell and organ dysfunction
      incurred by reperfusion. In the case of the heart, evidence for the causal
      involvement of such reactive molecular species includes (1) the increased
      formation of lipid peroxides, (2) the ability to mimic all facets of reperfusion
      injury (arrhythmias, contractile and vascular dysfunction, infarct extension) by
      exogenously applying reactive oxygen species, and (3) the propensity of a great
      variety of antioxidative and radical scavenging measures to afford
      cardioprotection during reperfusion. Potential sources of reactive oxygen
      metabolites in the reperfused heart are the mitochondrial redox-chain,
      endothelial enzymes such as cyclooxygenase, monoaminooxidase, NO-synthase and
      xanthine oxidase, and formed blood constituents (platelets, monocytes,
      granulocytes). According to our own results, adenosine, endogenously formed in
      the heart during ischemia, rapidly enhances adhesion of granulocytes introduced
      into the coronary system at reperfusion. Furthermore, small numbers of these
      cells suffice to induce contractile dysfunction in an isolated guinea pig heart
      model of ischemia-reperfusion injury, the major mediator of damage being HOCl.
      The striking disparity between the enormous volume of experimental data
      supporting involvement of reactive oxygen metabolites in reperfusion damage and
      the virtual lack of clinical-therapeutic regimens employing anti-oxidative
      measures is largely due to a still rudimentary knowledge of the homeostatic
      control of formation and removal of radicals and oxidants. In particular, the
      inability to correctly assess the individual time-course and extent of oxidative
      stress seems to be a major problem. Also, confounding issues such as
      compartmentation of radical formation as opposed to radical scavenging and the
      unwitting down-regulation of endogenous protective systems (e.g., of uric acid in
      the course of inhibiting xanthine oxidase) need to be resolved. On the other
      hand, we have been able to demonstrate protection by ACE inhibitors elicited via
      endothelially produced nitric oxide (a scavenger of O2- and OH) in the isolated
      heart. Thus, enhancement of endogenous protection may offer a perspective for
      mitigating against reperfusion damage.

PMID- 8154163
TI  - [Myocardial infarct: acute intervention].
AB  - Treatment strategies in acute myocardial infarction are directed toward
      limitation of infarct size and reduction of frequency of complications. This goal
      is best achieved by early reperfusion of ischemic myocardium. All trials
      comparing thrombolytic treatment in acute myocardial infarction indicate that
      either streptokinase, APSAC, or rtPA reduce mortality significantly. Particularly
      patients at high risk (old patients, women) benefit most from thrombolytic
      treatment. Although, conservation of left ventricular function and risk reduction
      is best achieved by very early treatment, a reduction of mortality has even been
      shown if thrombolytic agents are if given before 12 hours after onset of
      symptoms. Primary PTCA is an attractive alternative to thrombolytic therapy
      particularly in patients with anterior wall myocardial infarction or cardiogenic
      shock. Routine PTCA early or late after thrombolytic treatment however does not
      alter the outcome of the patients. The value of rescue PTCA remains to be
      settled. Heparin as an adjunctive treatment of rtPA improves patency of the
      coronary arteries and reduces mortality. Newer anti-thrombotic agents like
      hirudin, argotraban, or monoclonal antibody 7E3 are even more promising for
      prevention of reocclusion after thrombolytic treatment. Of the conservative
      medical treatment aspirin, beta-blockade, nitrates, and magnesium all have been
      shown reduce mortality. Similar effects could not be proven for calcium
      antagonists or routine antiarrhythmic drugs. ACE-inhibitors are of value if given
      3 days after onset of symptoms.

PMID- 8154164
TI  - [Introductory speech of the 59th Annual Congress of the German Society of
      Cardiovascular Research, Mannheim, 15-17 April 1993].

PMID- 8154165
TI  - [Peripheral arterial occlusive disease--acute intervention and after-care].
AB  - Acute ischemia in peripheral arterial occlusive disease due to progressive
      atherosclerosis is most commonly caused by thrombotic or thromboembolic events.
      Such a condition is a threat to both the limb and the life of a patient which
      requires rapid therapeutic decisions based on close cooperation between vascular
      surgeons, angiologists and radiologists. In complete ischemia with sensomotoric
      deficit and in suprainguinal occlusions surgical management remains the treatment
      of choice. Patients with incomplete ischemia and infrainguinal occlusions and
      patients unfit for major vascular surgery are appropriate candidates for local
      thrombolysis and percutaneous revascularization procedures. Available data on the
      main thrombolytic agents fail to show convincing difference between these drugs
      with regard to their efficacy and safety. Full heparinization is recommended
      before any definite therapy, after thrombolysis and if necessary after
      percutaneous transluminal angioplasty (PTA). Antiplatelet drugs should be given
      before and after reconstructive surgery and PTA and following heparinization
      after thrombolysis and PTA. In all conditions long-term treatment with
      antiplatelet drugs is recommended.

PMID- 8154166
TI  - [Conservative therapy of peripheral arterial occlusive diseases].
AB  - Treatment of peripheral arterial occlusive disease depends upon pathogenesis,
      localization, and severity of disease. For patients with intermittent
      claudication the goal should be an increased reserve capacity, and in critical
      limb ischemia therapy should aim at restitution of the basal metabolism.
      Hemodynamic as well as hemorheologic improvements act in this way. Considering
      the pathophysiological, pathobiochemical, and clinical aspects of the individual
      patient, both mechanisms can be used systematically. The efficacy of therapeutic
      principles in angiology has not been confirmed through large-scale, randomized,
      placebo-controlled, long-term follow-up studies until now, in contrast to the
      field of cardiology.

PMID- 8154167
TI  - [Ischemia--reliable results of therapy, operation and angioplasty--in coronary
      disease].
AB  - Randomized studies have shown that coronary bypass-surgery is effective in
      prolonging survival and reducing symptoms in various groups of patients with
      coronary artery disease, when compared with medical therapy alone. This effect is
      most pronounced and stable in patients who received an internal-mammary-artery
      graft. Therefore internal-mammary-artery grafting for lesions of the left
      anterior descending coronary artery is preferable whenever indicated and
      technically feasible. While percutaneous transluminal coronary angioplasty is
      effective in improving symptoms of angina pectoris, beneficial effects on
      survival have not yet been shown. In randomized trials of PTCA versus bypass
      surgery acute results were comparable. During follow-up significantly less re
      interventions and more angina-free patients were seen in the bypass-groups,
      indicating a more stable result after bypass surgery. In older patients with a
      higher mortality and rate of cerebral vascular events during surgery, a
      palliative PTCA of the culprit lesion may be superior to the bypass-operation.
      For the often used "unproven" indications for PTCA (silent ischemia, infarct
      related artery in asymptomatic patients, isolated proximal LAD-stenosis, acute
      myocardial infarction, cardiogenic shock) larger randomized trials should be
      awaited to prove the effectiveness of PTCA in these settings.

PMID- 8154168
TI  - [Prognostic criteria for initial success in PTA and catheter thrombolysis].
AB  - The preliminary results of 1063 percutaneous dilatations (PTA) of iliac or
      femoropopliteal arteries were evaluated in order to establish pre-existing
      clinical or morphological criteria with possible influence on the early success
      rate. Early failure was defined as the impossibility to eliminate the arterial
      occlusion or re-occlusion within 48 hours. Regarding the clinical criteria the
      combination of long duration and advanced stage of the disease unfavourably
      influenced the primary success rate (failure rate of 40%). Morphological factors
      such as length of occlusion over 10 cm, poor run-off or existence of large
      arterio-venous shunts had an even worse influence on the early success rate
      (failure rate of 50-60%).

PMID- 8154169
TI  - [Immunohistologic cell characterization of tissue of primary and re-stenoses].
AB  - Smooth muscle cells and macrophages are essential parts of arteriosclerotic
      lesions. This study should enable the analysis of different functional and
      morphological features of cells in primary and restenotic biopsies. Therefore
      detection of specific cell markers in human arteriosclerotic material derived
      from directional coronary atherectomy (DCA) of primary and restenotic lesions was
      used. Cryosections (2-4 microns) were stained immunohistologically (44 samples
      from 27 patients, 12 restenosis) with monoclonal antibodies. For further analysis
      antibodies against 5B5 (Prolylhydroxylase), alpha-actin, desmin and collagen I
      and IV were used. Endothelial structures (CD 31), T-cells and monocyte derived
      macrophages (CD 68, KP 1) were detected. In a second set-up alpha-actin and CD 68
      were double-labelled. Semi-quantitative analysis in relation to total cell count
      was performed. The tissue removed consisted quantitatively of 78% intima- and 22%
      media-compartments and thrombus. 40% of the intimal area was comprised of low
      cellular compartments and in 57% high cellularity and foam-cells were found. In
      high cellular compartments 81% of the cells were positive for alpha-actin, only
      13% of these cells were also positive for desmin. In intimal compartments in 58%
      of the cells macrophages were detected by CD-68 marker immunohistologically. 87%
      of these cells showed the expression of the 5B5 antigen (Prolylhydroxylase), in
      90% monocytic antigenes were detected. Typical foam cells were not alpha-actin
      positive, whereas 40% of the CD 68 positive cells were alpha-actin positive. In
      myofibroblastic cells, positive staining with 5B5, collagen IV and extracellular
      matrix (collagen I) was present. Staining with antibodies against contractile
      filaments was diminished compared to the media compartments.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8154170
TI  - [Transcutaneous electric muscle stimulation--a "new" possibility for the
      prevention of thrombosis?].
AB  - Adhesive electrodes for transcutaneous electrical stimulation of the calf were
      applied on the skin of 11 patients with ruptures of the fibular ligaments
      (treated surgically or conservatively with cast) during the period of
      immobilisation (four weeks). Muscle stimulations were performed several times a
      day over a period of at least 15 minutes with a small rechargable muscle
      stimulation apparatus. Duplex sonography revealed that a significant rise of the
      venous flow velocity could be achieved with an 8.5-fold increase of the venous
      flow velocity as measured over the popliteal vein. Transcutaneous muscle
      stimulation might move to be a "new" efficient method for the prophylaxis of deep
      vein thrombosis.

PMID- 8154171
TI  - Low-molecular-weight heparins: a decade with the new class of antithrombotic
      agents.
AB  - Low molecular weight heparins (LMWH) are progressively replacing standard
      unfractionated heparin (UFH) for prophylaxis of venous thromboembolism,
      especially following surgery. LMWHs are also being used for treatment of
      established deep venous thrombosis. The main advantages of this new class of
      antithrombotic agents as compared with UFH are: 1) a new dosing concept (one
      single subcutaneous administration instead of two or three), based on improved
      bioavailability and prolonged half-life; 2) an improved efficacy: safety ratio
      both in the prophylactic and therapeutic settings. Despite these benefits, some
      unsolved issues remain to be addressed in specific clinical trials before LMWHs
      can definitively replace UFH in all previous indications of UFH. These issues
      include the use of LMWHs in patients with arterial thrombosis or myocardial
      infarction (e.g. in conjunction with thrombolytic treatment), and in patients
      with pulmonary embolism. In addition, the easy use of LMWHs opens the way towards
      outpatient therapy of proximal vein thrombosis but this modality needs to be
      fully assessed in well-designed clinical trials before definitive recommendations
      can be given.

PMID- 8154172
TI  - [Percutaneous balloon dilatation of isolated lesions of the calf arteries in
      critical ischemia of the leg].
AB  - Between 1990 and 1993 we performed 42 percutaneous transluminal balloon
      angioplasties (PTA) in 30 patients with isolated lesions of crural arteries and
      limb threatening ischaemia. The average age of the patients was 70.5 years, 90%
      were diabetics. With low-profile balloon catheters between 2 and 4 mm we
      dilatated 15 tibioperoneal trunks, 12 anterior tibial arteries, 3 posterior
      tibial arteries and 12 peroneal arteries. Initial success was achieved in 83% of
      the dilatations with an average increase of ankle-brachial index of 0.18. After
      PTA two groin haematomes as the only complications were observed. In 22 cases
      healing of the acral lesions under local surgical treatment was seen. Two of the
      clinical unsuccessful patients required popliteopedal bypass surgery and 5 below
      knee amputation because of lacking reconstructive possibilities. The follow-up
      period varied from 1 to 35 months (mean 10.3 months). Life table analysis showed
      a cumulative limb salvage rate of 82% after one and two years. The PTA of
      infrapopliteal artery stenoses and occlusions is considered as an effective and
      safe therapy modality to avoid below-knee amputation in patients with limb
      threatening ischaemia.

PMID- 8154173
TI  - Digitized nailfold capillaroscopy.
AB  - An image processing system was developed to quantify the morphometry of nailfold
      capillaroscopy. Image acquisition was performed with a macrophotographic
      technique, and images are digitized using a video camera and an image processing
      system. After an image segmentation, the microcomputer determines in an
      interactively defined window, the following parameters: capillary loop width and
      length, capillary surface area, distance from the tip of the capillary loop to
      the dermal edge, distance between two adjacent capillaries. Other parameters can
      be computed from these: linear density, density and dispersion index of the
      distance between two adjacent capillaries (variation coefficient). A validation
      study, comparing 20 capillary fields from healthy subjects and 19 capillary
      fields with "SD-pattern", provided from patients with systemic sclerosis or
      dermatomyositis, reveals significant differences of all these parameters between
      the two groups, consistent with the literature. This study also isolates two
      parameters which are the best predictors of the "SD-pattern": the mean capillary
      surface and the capillary density (capillaries/mm2). The morphometric parameters
      obtained through this system are suitable for evaluation of microangiopathy and
      should be evaluated for diagnosis and follow-up of vascular acrosyndromes,
      systemic sclerosis, Raynaud phenomenon and allied conditions in clinical
      conditions.

PMID- 8154174
TI  - [False aneurysm after reconstruction for peripheral arterial occlusive disease.
      Observations over 15 to 25 years].
AB  - In an earlier study patients operated for arterial occlusive disease have been
      observed for at least 15 to 25 years. They have now been analysed for incidence,
      localization, time of appearance and results of reoperation of anastomotic
      aneurysms. These are not only seen after prosthetic bypass--2/3 of 27 cases--with
      an incidence of 7.8%, but also after vein bypass (5.23%), semiclosed
      endarterectomy with dacron patch (2.59%) or vein patch (5.23%) and open
      endarterectomy with vein patch (7.14%). The incidence depends mainly upon the
      time of observation. They appear in the inguinal area in 38.5%, near the adductor
      canal in 27%, above the inguina in 19% and below the knee in 15%. They have to be
      expected earlier with prosthetic bypass. Mortality after reoperation is higher
      with aortoduodenal fistula (18.75%) than without (7.14%). The postoperative
      patency rate was about 65%, amputation occurred only after prosthetic bypass as
      primary procedure. The patency rate was 80% after 1 year, remained at this level
      so after endarterectomy for 10 years and dropped after prosthetic bypass after 4
      years considerably, leading to a high amputation rate within 15 years. Up to 10
      years most of the patients who died in the later period had an open
      reconstruction at death and had up to that time no walking problems. Death was
      due to coronary heart disease in 55.5% and cancer of the lung in 22.2%.

PMID- 8154175
TI  - Prosthetic vascular graft infection--defect covering with delayed vertical rectus
      abdominis muscular flap (VRAM) and rectus femoris flap.
AB  - Prosthetic vascular graft infection is associated with high rates of morbidity
      and mortality. When infections lead to an open exposure of vascular prosthesis
      special techniques may be necessary to cover tissue defects in regions with often
      very poor circulation/perfusion conditions. Even when there are large tissue
      defects associated with vascular prosthetic graft infections and exposure of
      prosthesis local cure can be achieved after radical debridement and defect
      coverage through transposition of myocutaneous flaps. The cases of two patients
      with open exposure of prosthesis in the groin who had been successfully treated
      by delayed vertical rectus abdominis muscular flap (VRAM) or rectus femoris
      rotation are presented. The contralateral VRAM myocutaneous flap is an excellent
      alternative if local measures fail to close large groin defects with exposed
      prosthesis. In addition the delayed flap rotation offers a greater safety in
      conditioning the vascularity of the flap.

PMID- 8154176
TI  - Acetylsalicylic acid--reocclusion--prophylaxis after angioplasty (ARPA-study). A
      randomized double-blind trial of two different dosages of ASA in patients with
      peripheral occlusive arterial disease.
AB  - We report on a randomized controlled clinical trial in patients with peripheral
      occlusive arterial disease who have been successfully treated with angioplasty.
      The efficacy and the rate of side effects of two doses of ASA (300 mg vs. 1000 mg
      daily) have been compared during a treatment period of 6 months after
      angioplasty. It was planned to include a total of 600 patients in the trial. A
      predefined interim analysis of 200 patients which was performed after the actual
      inclusion of 218 patients showed identical reocclusions rates and a very similar
      frequency of side effects in both treatment groups. The study was then terminated
      since it was not expected that further continuation would lead to a relevant
      difference between the two treatment groups concerning efficacy or side effects.
      Patients already included in the trial at the interim evaluation were included in
      the final analysis, leading to a total number of 223 patients. Finally 112
      patients had been randomized to receive a daily dose of 300 mg ASA and 111
      patients to receive 1000 mg ASA. Reocclusions occurred in 18 patients (16%) on
      300 mg of ASA/day and in 20 patients (18%) receiving 1000 mg ASA/day. The study
      was interrupted because of side effects in 27 patients (24%) in the 300 mg/day
      group and in 27 patients (24%) in the 1000 mg/day group. Mostly subjective
      gastric complaints were the cause of interruption in 17 patients (15%) in the 300
      mg group and in 21 patients (19%) receiving the higher dose regimen. So the
      reocclusion rate was identical in both dosage-groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8154177
TI  - [Treatment of venous stenoses and occlusions of benign etiology with vascular
      endoprostheses: a new, non-operative therapeutic concept].
AB  - 8 patients (7 women and 1 man, age between 35 and 66 years, mean 46.3) suffering
      from a stenosis or occlusion of the pelvic or superficial femoral vein after
      surgical or percutaneous intervention were successfully treated with endovascular
      stents of the wallstent type. Clinical and Doppler sonographic as well as
      phlebographic controls showed patency of all stented lesions at followup times
      between 3 and 82 months (average 27 months). The use of percutaneous transluminal
      angioplasty (PTA) in the venous system in combination with implantation of self
      expanding vascular endoprostheses offer a new therapeutic modality to treat veins
      with stenosis or occlusion of benign etiology without surgical intervention.

PMID- 8154178
TI  - [Optimizing analgesia and procedure of retrograde venous perfusion in treatment
      of patients with peripheral arterial occlusive diseases].
AB  - Description of the 3-in-1-Block (Winnie) as an effective method of anaesthesia in
      retrograde venous perfusion as one therapy in arterial occlusive disease.
      Additional recommendations are given to achieve a homogeneous distribution of the
      substances in the limb.

PMID- 8154179
TI  - Ruptured abdominal aortic aneurysm and concomitant serious diseases.
AB  - A case of ruptured aortic aneurysm in connection with an operation for gastric
      cancer is described. Risk factors for ruptures are discussed. An active approach
      even in serious concomitant disease in elderly people is recommended.

PMID- 8154180
TI  - A comparative analysis of distinctive features of yeast protein sequences.
AB  - The recently published sequence of yeast chromosome III (YCIII) provides the
      longest continuous stretch of a eukaryotic DNA molecule sequenced to date (315
      kb). The sequence contains 116 distinct AUG-initiated open reading frames of at
      least 200 codons in length, more than 50 of which had not been described
      previously nor bear significant similarity to known proteins. We have analysed
      the YCIII known and putative protein sequences with respect to significant
      statistical features which might reflect on structural and functional
      characteristics. The YCIII proteins have striking similarities and differences in
      their sequence attribute distributions compared to the corresponding
      distributions for all available yeast sequences and other protein collections.
      Nine examples of YCIII proteins with distinctive sequence features are discussed
      in detail.

PMID- 8154181
TI  - A series of yeast shuttle vectors for expression of cDNAs and other DNA
      sequences.
AB  - Expression/shuttle vectors for the yeast Saccharomyces cerevisiae have usually
      been large plasmids with only one or a small number of sites that are suitable
      for cloning and expression. We report here the construction and properties of a
      series of 12 expression vectors with multiple (four to eight) unique sites in
      their polylinkers which allow directional cloning and expression of DNA sequences
      under four different promoters. Eleven of these plasmids replicate at high copy
      number in Escherichia coli, and all have the yeast TRP1 gene, and the 2 microns
      origin including REP3 sequence, allowing selection and high copy number
      replication in yeast. Six of the plasmids are designed for the construction and
      selection and high copy number replication in yeast. Six of the plasmids are
      designed for the construction and selection of cDNA libraries from various
      eukaryotic organisms, allowing directional cloning and expression of cDNAs. All
      of these six have similar polylinkers containing a unique promoter proximal EcoRI
      site and a unique promoter distal XhoI site, allowing for directional cloning and
      expression of 'ZAP'-type cDNAs. cDNAs that complement a wide variety of yeast
      mutants can be selected from libraries constructed in this way. The four
      alternative promoters, ADH2, PGK, GAL10 and SV40 were compared for their relative
      activity, both in E. coli and in yeast. All yeast promoters showed substantial
      activity in E. coli with ADH2 showing the highest activity. ADH2 also was well
      regulated in yeast, showing very high relative activity under derepressing
      conditions. cDNAs selected by genetic complementation from libraries constructed
      in these vectors should be easily subclonable into other vectors, allowing
      expression in different eukaryotic organisms, DNA sequencing or site-directed
      mutagenesis.

PMID- 8154182
TI  - A series of yeast/Escherichia coli lambda expression vectors designed for
      directional cloning of cDNAs and cre/lox-mediated plasmid excision.
AB  - A series of Saccharomyces cerevisiae/Escherichia coli lambda/plasmid expression
      vectors have been constructed which allow easy excision of the plasmid sequences
      from lambda. Features of six are described, and two designated lambda PG15 and
      lambda AD5, are characterized in detail. Transcription of cloned sequences is
      controlled by the alternative promoters, ADH2, PGK, GAL10 and SV40 early, and by
      the CYC1 transcriptional terminator. Unique EcoRI and XhoI restriction sites in
      the intervening polylinker make these lambda vectors compatible for directional
      cloning of 'ZAP'-synthesized cDNAs. Inserted DNAs have been previously shown to
      have high levels of the genetic activity in both S. cerevisiae and E. coli,
      allowing these vectors to be used for genetic complementation in both species.
      Plasmid recovery from the lambda vector is mediated by the activity of the cre
      encoded enzyme upon lox sequences flanking the plasmid and adjoining the lambda
      arms. The plasmids contain the yeast 2 microns origin and E. coli pBR322 origin,
      the URA3 or TRP1 yeast selectable markers, and ampicillin-resistance marker in E.
      coli. The usefulness of the lambda PG15 and the lambda AD5 cloning vectors was
      demonstrated by constructing large Neurospora crassa cDNA libraries. The lambda
      PG15-N. crassa library was used to infect purE, purC and trpC mutants of E. coli,
      and complemented and/or suppressed prototrophic colonies were selected. The
      flexibility and power of this system for cloning of cDNAs is discussed.

PMID- 8154184
TI  - Role of O-acetylhomoserine sulfhydrylase in sulfur amino acid synthesis in
      various yeasts.
AB  - Mutants defective in O-acetylhomoserine sulfhydrylase (OAH-SHLase) were obtained
      in five yeast strains representative of different yeast genera: Saccharomyces
      cerevisiae, Kluyveromyces lactis, Yarrowia lipolytica, Schizosaccharomyces pombe
      and Trichosporon cutaneum. In vitro, in all five strains, the enzyme also had O
      acetylserine (OAS) sulfhydrylase activity so it is a 'bifunctional' OAH/OAS
      SHLase (Yamagata, 1989). The enzyme was only found to be essential in S.
      cerevisiae (OAH SHLase-negative mutants are auxotrophs). Its impairment in K.
      lactis caused a slower growth rate and a decrease of the sulfur amino acid pool.
      In T. cutaneum only the pool was affected whereas in Y. lipolytica and S. pombe
      the lesion caused no change in the growth rate nor in the pool. In all strains
      where OAH SHLase-negative mutants were prototrophs, a monofunctional OAS
      sulhydrylase was detected. The results indicate that OAH SHLase may play
      different physiological roles in various yeasts.

PMID- 8154183
TI  - Accurate initiation of mRNA synthesis in extracts from Schizosaccharomyces pombe,
      Kluyveromyces lactis and Candida glabrata.
AB  - We demonstrate the successful adaptation to other yeast species of a protocol
      previously described for production of transcriptionally active whole cell
      extracts from Saccharomyces cerevisiae (Woontner and Jaehning, 1990, J. Biol.
      Chem. 265, 8979-8982). Extracts prepared from Schizosaccharomyces pombe,
      Kluyveromyces lactis and Candida glabrata were all capable of initiating
      transcription from a template containing the S. cerevisiae CYC1 TATA box fused to
      a G-less cassette. Transcription in all of the extracts was sensitive to
      inhibition by alpha-amanitin, indicating that it was catalysed by RNA polymerase
      II, and was dramatically stimulated by the chimeric activator GAL4/VP16. The
      different extracts used different subsets of a group of three initiation sites.

PMID- 8154185
TI  - Sequencing and analysis of 51.6 kilobases on the left arm of chromosome XI from
      Saccharomyces cerevisiae reveals 23 open reading frames including the FAS1 gene.
AB  - We have sequenced two segments containing a total of 51.6 kb of the left arm from
      chromosome XI of Saccharomyces cerevisiae. The first segment of 38.5 kb contains
      18 open reading frames (ORFs) of more than 100 amino acid residues. Five ORFs
      encode known yeast genes, including the fatty acid synthase gene (FAS1). Three
      new yeast genes were discovered with homologies to non-yeast genes and ten new
      genes without homologies to any known sequences. The second segment of 13 kb
      contains five ORFs with two known yeast genes and three unknown genes. The
      sequences from cosmid pUKG041 were obtained entirely with the walking primer
      strategy resulting in a very low overall sequence redundancy of 2.8 and an
      average reading length of 443 bases.

PMID- 8154186
TI  - The complete sequence of a 15,820 bp segment of Saccharomyces cerevisiae
      chromosome XI contains the UBI2 and MPL1 genes and three new open reading frames.
AB  - As part of the EEC yeast genome program, a fragment of 15,820 bp from the right
      arm of Saccharomyces cerevisiae chromosome XI has been sequenced. This fragment
      corresponds roughly to the centromere-distal half of cosmid pUKG046 and to a
      small fragment of cosmid pUKG096, which are located approximately 150 kb from the
      centromere. It contains four open reading frames (ORFs) which encode potential
      proteins of more than 100 amino acid residues, as well as the UBI2 gene which
      carries an intron and does not show up as an ORF in the sequence analysis
      programs. One of the putative proteins, YKR412, is very rich in serine and has
      significant homology at the carboxyl end to Nopp140 phosphoprotein. YKR413 has
      several predicted transmembrane domains. YKR15, which has been recently cloned as
      the MPL1 gene, encodes a polypeptide that shows homologies to myosin heavy chain
      and to the cytoskeleton protein Uso1.

PMID- 8154187
TI  - Sequencing and functional analysis of a 32,560 bp segment on the left arm of
      yeast chromosome II. Identification of 26 open reading frames, including the KIP1
      and SEC17 genes.
AB  - We report here the DNA sequence of a segment (alpha 1006.13: YBLO5) of chromosome
      II of Saccharomyces cerevisiae, extending over 32.5 kb. The segment contains 26
      open reading frames (ORFs) from YBLO501 to YBLO526. YBL0505 corresponds to the
      SEC17 gene and YBL0521 to the KIP1 gene. YBL0516 contains an intron, YBL0513
      shows homology with the RAT protein phosphatase and YBL0526 contains a zinc
      finger motif. Disruption of 14 genes by insertion of a URA3 cassette has been
      performed and these mutants were analysed for their mating and sporulation
      ability, and for their growth on different carbon sources. YBL0515 and YBL0526
      ORFs seem to be involved in the sporulation process.

PMID- 8154188
TI  - Low-affinity glucose carrier gene LGT1 of Saccharomyces cerevisiae, a homologue
      of the Kluyveromyces lactis RAG1 gene.
AB  - A low-affinity glucose transporter gene of Saccharomyces cerevisiae was cloned by
      complementation of the rag1 mutation in a strain of Kluyveromyces lactis
      defective in low-affinity glucose transport. Gene sequence and effects of null
      mutation in S. cerevisiae were described. Data indicated that there are multiple
      genes for low-affinity glucose transport.

PMID- 8154190
TI  - Current awareness on yeast.

PMID- 8154189
TI  - The sequence of a 17.5 kb DNA fragment on the left arm of yeast chromosome XI
      identifies the protein kinase gene ELM1, the DNA primase gene PRI2, a new gene
      encoding a putative histone and seven new open reading frames.
AB  - A 17.5 kb DNA fragment of chromosome XI, located between the genetic loci mif2
      and mak11 was sequenced and analysed. Ten open reading frames were identified.
      Two of them are the previously sequenced genes ELM1 and PRI2, two (YKL253 and
      YKL256) show homologies to proteins from other organisms and one (YKL262) to
      yeast and mouse histone.

PMID- 8154191
TI  - Quality circles and their potential application to rural health care in Papua New
      Guinea.
AB  - A quality circle is a group of service providers who meet regularly to solve
      problems relating to the quality of their work. This is an example of bottom-up
      rather than top-down management which has found considerable success in the
      industries of the developed world. This article describes the principles which
      govern the operation of quality circles, the expected benefits and how best to
      introduce them. The problems relating to the provision of quality health care in
      rural areas and the potential application of the quality circle methodology are
      discussed.

PMID- 8154192
TI  - Can medical audit be practised in district hospitals in Papua New Guinea?
AB  - Medical audit has become a statutory requirement for all specialties in many
      countries throughout the world, but apart from obstetric care has not been a
      routine part of clinical practice in Papua New Guinea. As the majority of people
      in Papua New Guinea live in rural areas served by a district hospital, medical
      audit will fail to contribute to raising the standards of health care unless it
      is also enthusiastically adopted by physicians in the rural districts. It is
      incumbent on all physicians to accept the leadership role that the health service
      expects of them to ensure the quality of care for their patients. Unlike factors
      relating to the quality of service, the quality of care can only be assessed by
      physicians. The methods to be used will vary according to the staffing,
      facilities and case-mix of the individual district hospital. The major
      constraints to the implementation of medical audit are discussed and some
      solutions are offered. It is concluded that medical audit can, and should, be
      practised in district hospitals in Papua New Guinea.

PMID- 8154193
TI  - Quality assurance in surgery: surgical audit in the developing world.
AB  - Surgical audit is an essential component of quality assurance in surgery,
      particularly in the developing world, where resources and skills are limited. The
      structure, process and outcome of care can be measured. With regard to structure,
      in developing countries the delivery of care is influenced by lack of resources
      and access to surgical skills. The number of operations not being done needs to
      be estimated as well as the throughput of surgery. With regard to process, ward
      rounds and writing in case-notes are daily activities which affect the process of
      care. The use of investigations, particularly ones which are expensive or have
      risks, should be audited to ensure there is maximum cost-benefit to both the
      patient and the health care system. Surveys of patient perception of quality are
      also important. With regard to outcome, surgeons measure quality by auditing
      complications and mortality. Audit and mortality meetings should be held to
      discuss problems and how they can be avoided. The factors responsible for 34
      deaths at Port Moresby General Hospital are presented. To be reliable, mortality
      audits should grade illness severity, for example, by using the Glasgow Coma
      Scale to grade the severity of a head injury. Where mortality rates are low, for
      example, in patients with fractures, long-term follow-up of disability may be a
      more appropriate measure of outcome and quality than mortality rates.

PMID- 8154194
TI  - Criteria audit: making use of existing data.
AB  - The first steps in setting up a criteria audit are presented with the aim of
      serving as a guide for starting quality assurance activities in Papua New Guinea.
      These activities need to be based on data, and the systematic and critical
      analysis of any available data on the process or outcome of health care delivery
      is a simple, cheap and useful basis for its improvement. Criteria are defined and
      the completeness and relevance of the data audited are discussed. Recommendations
      on the use of available recorded data and on the improvement of record-keeping
      practices are made.

PMID- 8154195
TI  - Australian Community Health Association Practice Standards and their application
      for primary health care in Papua New Guinea.
AB  - This paper describes the Australian Community Health Association Practice
      Standards (CHASP) and their application in the CHASP review process as a model
      that could be emulated to improve the quality of primary health care delivery in
      Papua New Guinea. The characteristics which could be beneficially emulated in
      Papua New Guinea are the comprehensive nature of the standards and their wide
      applicability, the balance contained in their development and application between
      the inputs of technical expertise and local involvement, and the structured
      nature of the CHASP review process itself. A model is proposed of how the CHASP
      standards and review process could be fruitfully used in Papua New Guinea to
      improve the quality of rural health care delivery.

PMID- 8154196
TI  - Vaccines in the national immunization programme.
AB  - Papua New Guinea has been providing expanded immunization services for more than
      14 years. While immunization coverage has risen dramatically, recent surveys have
      raised serious questions regarding vaccine potency at the service delivery level.
      Operational practices in vaccine distribution and in the delivery system have
      been identified in this paper. The international and national standards for
      vaccine management are described along with the main requirements for maintaining
      vaccine potency. Quality assurance measures, the responsible personnel and the
      appropriate intervention points are detailed, along with easily applied
      guidelines for implementation. An approach to assessing the effectiveness of the
      quality assurance measures is proposed.

PMID- 8154197
TI  - Nursing audit: measuring the quality of nursing care.
AB  - The quality assurance initiative was taken in 1984 in Papua New Guinea as a
      result of numerous public criticisms of the services and the care given and/or
      observed by patients and the community. The approach to quality assurance chosen
      for this nursing audit is a problem-oriented and patient-focused structure,
      process and outcome method based on World Health Organization principles and
      adapted from the Dynamic Standard Setting System.

PMID- 8154198
TI  - National Quality Assurance Programme for rural and provincial laboratory services
      in Papua New Guinea.
AB  - The expansion of laboratory services in Papua New Guinea in recent times,
      particularly at the rural health centre level, in support of public health
      laboratory activities has stressed the need to monitor the technical performance
      of laboratory workers. With this in mind, a National Quality Assurance Programme
      (NQAP) was devised following a successful trial in the Momase Region in 1990. The
      NQAP has expanded rapidly and met with good response and high levels of
      achievement by participating laboratories nation-wide. Future plans are to
      develop a National Quality Assurance Committee and work towards an accreditation
      scheme in Papua New Guinea.

PMID- 8154199
TI  - Prospects for quality assurance in Papua New Guinea.

PMID- 8154200
TI  - Quality assurance in transition.
AB  - This paper outlines the early approaches to quality assurance, and its transition
      from business to health care. It then describes the development of the more
      recent trends in quality assurance of Total Quality Management and Continuous
      Quality Improvement and discusses the strengths and weaknesses of these
      approaches. The paper then goes on to show how these approaches have been
      modified for application to peripheral health services in developing countries
      through the work of the Primary Health Care Operations Research Project and the
      Quality Assurance Project.

PMID- 8154201
TI  - Quality of health services in Papua New Guinea: what do we know?
AB  - The discussion of quality issues in Papua New Guinea requires that attention be
      focused on what is known about the actual quality of the health care provided in
      Papua New Guinea. Since 1987 there has been increasing evidence that there are
      serious deficits in the quality of care in rural areas and that there are similar
      problems in the country's hospitals. This paper summarizes what is known and
      discusses the implications for the development of quality assurance activities in
      Papua New Guinea. The paper concludes that many of the deficiencies observed are
      amenable to improvement through simple and inexpensive means and that with
      sustained commitment, improvements are achievable.

PMID- 8154202
TI  - An overview of quality issues in health services.
AB  - This paper establishes a common framework for understanding some of the quality
      issues in health services. It presents definitions and examples of the most
      frequently used and the most frequently confused terms related to quality. The
      meanings of quality, quality of health care, quality assessment, quality
      assurance, quality control and total quality management are described with
      illustrative examples. The major approaches to quality assessment and its uses
      are discussed. A model of the quality assurance process is explained as well as
      the issues surrounding quality assurance in the settings of primary and secondary
      health services.

PMID- 8154203
TI  - [An improvement in the dispensary registration of the mentally ill of advanced
      age].
AB  - The paper reviews the results of registration reorganization in one of the Moscow
      gerontological psychiatric consultations. Two groups of psychic pathology were
      recognized: advanced psychoses and dementia (1168 patients), nonpsychotic
      diseases of the nonpsychotic level were registered in the group of "consultative
      follow-up". Hospitalization in this group made up 38 cases. The analysis showed
      that patients of advanced age require a special approach in follow-up,
      examination and hospitalization planning.

PMID- 8154204
TI  - [A case of Rud's syndrome].
AB  - A twenty-two-year-old patient is described who developed in the presence of
      congenital ichthyosis, osseous system developmental abnormalities, and
      psychopathologic personality disorders fits with loss of consciousness and
      seizures whose epileptic nature was proved by EEG studies. Clinical symptom
      complex found in this patient conformed to description of a rare hereditary
      disease, Rud's syndrome. The role of hereditary abnormalities in epilepsy
      development is discussed, as are problems of differential diagnosis of Rud's
      syndrome and other rare hereditary diseases with combinations of ichthyosis,
      epilepsy, and intellect disturbances.

PMID- 8154205
TI  - [Knowledge about human brain mass].

PMID- 8154206
TI  - [The family of the alcoholic as a system].

PMID- 8154207
TI  - [The epidemiological aspects of a study of hereditary nervous system diseases in
      Amur Province].
AB  - The prevalence of neurogenetic diseases per 100,000 was studied in Amur Province
      [correction of Territory]. Charcot-Marie's neural amyotrophy held the lead,
      Huntington's chorea ranked next. Among the multinational population, the diseases
      were detected among the Russians, but they were absent in the Evenki. Out of 225
      cases, 138 males were afflicted. The most unfavourable factors that predisposed
      to the disease proved to be infectious processes, toil, and stresses.
      Epidemiological studies of neurogenetic diseases provide highly valuable
      information on the migration of abnormal genes and promote to the timely
      organization of therapeutical and preventive measures.

PMID- 8154208
TI  - [The clinico-epidemiological characteristics of myotonias in Saratov Province].
AB  - The paper summarizes data on the epidemiology and clinical polymorphism of the
      major types of myotonias. Presents both familial and sporadic cases of myotonia
      congenita, atrophica, dystrophica, and Eulenburg's [correction of Eilenburg's]
      paramyotonias. Describes the clinical picture of Thomsen's disease in childhood.
      Discusses the types of disease inheritance and nosological entities of myotonias.
      The material has been obtained from the studies performed over 25 years, which
      allows the course of the disease to be followed up in families and in
      individuals, and enables the patients' migration in the region and outside to be
      traced.

PMID- 8154209
TI  - [Myotonia dystrophica].
AB  - Dystrophic myotonia is a sufficiently rare disease inherited mainly by the
      autosomal dominant type. Clinical picture is characterized by the myotonic,
      myopathic, and endocrine-autonomic syndrome. A clinical, genetic, and
      electromyographic study was carried out to elucidate the problem of this
      condition inheritance, its intra- and interfamilial clinical polymorphism, and
      effects of environmental factors on its course and outcomes.

PMID- 8154210
TI  - [The Arnold-Chiari anomaly: magnetic resonance tomographic data and the clinical
      manifestations].
AB  - Magnetic resonance tomographic findings and clinical symptoms were compared by
      using the results of 596 studies. The clinical diagnoses and types of Arnold
      Chiari's anomaly, which were revealed by magnetic resonance tomography as groups
      I, II, and III were also evaluated. A contribution of fluid dynamic disorders,
      including intracranial hypertension and hydrocephalus, was assessed. No
      relationship was found between the clinical manifestations and the ascending
      degree of cerebellar tonsils. The combination of Arnold-Chiari's anomaly with
      syringomyelia and osteochondrosis and a role of magnetic resonance tomography in
      the identification of the anomaly for correct choice of therapy in spinal
      pathology were shown. It was concluded that magnetic resonance tomography should
      be used in all cases of spinal diseases or suspected diseases of the craniospinal
      transition.

PMID- 8154211
TI  - [The Kearns-Sayre syndrome].
AB  - The paper describes Kearns-Sayre's syndrome, a rare hereditary neuromuscular
      disease, in a patient aged 17 years. The clinical picture of the disease had a
      classical triad: external ophthalmoplegia, pigmentary retinopathy, and cardiac
      conduction disturbances. This triad was supplemented with other polymorphous
      symptoms characteristic of the syndrome, such as moderate myopathic syndrome,
      hemeralopia, physical infantilism, hypogonadism, pyramidal syndrome. Bifascicular
      block in the His-Purkinje system was accompanied by mitral prolapse. The problems
      of early diagnosis of the syndrome and choice of adequate therapeutical methods
      are discussed.

PMID- 8154212
TI  - [Congenital muscular dystrophy with leukoencephalopathy].
AB  - The paper reports a case of the western-type congenital muscular dystrophy in a 5
      year-old boy who showed generalized myasthenia and hypotrophies, flexor
      contractures in the large joints of legs and arms, areflexia of deep reflexes.
      Examining the biopsy specimens of the musculus quadriceps femoris revealed
      changes typical of muscular dystrophy. The level of serum creatine kinase was
      elevated. Electromyography showed changes characteristic of muscular lesion. An
      emphasis is laid on his asthenic constitution, hydrocephalic skull, lowly located
      ears, and a small mouth. Despite preserved intellect and no focal neurological
      symptomatology, brain computed tomography indicated a diffuse decrease in the
      density of the substantia alba in the cerebral hemispheres. The paper also
      provides references to papers which emphasize that neurological symptoms will
      inevitably develop in such patients in future.

PMID- 8154213
TI  - [Spastic torticollis in children (the problems of the clinical picture, treatment
      and nosological specificity)].
AB  - Twenty-two cases with spastic torticollis in children are analyzed. This syndrome
      was the only suffering in ten children and was a component of generalized forms
      of deforming muscular dystonia in twelve. In such cases the time course of
      spastic torticollis clinical picture, possible alteration of tonic and clinical
      forms, involvement as a rule of hands and shoulders muscles permit regarding this
      condition as a variant of local deforming muscular dystonia and not an individual
      hyperkinesis. The efficacy of routine drug therapy administered to these patients
      directly depended on the form and pattern of spastic torticollis. Positive shifts
      were observed in 90.9% of patients, in 40.9% a marked positive effect was
      attained.

PMID- 8154214
TI  - [Neuro-AIDS in children].
AB  - The paper analyzes the results of studying nervous diseases in children with HIV
      infection. A total of 57 children aged 1.5 to 16 years who had different stages
      of AIDS were examined. HIV-related encephalopathy, encephalopathy with the
      polyneuropathy syndrome, encephalomyelopolyneuritis, mixed AIDS-related
      encephalopathy and perinatal encephalopathy, as well as the myopathic syndrome
      were identified. The affliction of the nervous system was more severe with an
      earlier history of infection. The clinical syndromes were supported by
      electromyographic indices.

PMID- 8154215
TI  - [Autonomic vascular dystonia with syncopal attacks and its correlation with
      epilepsy in children and adolescents].
AB  - Ninety children and adolescents with syncopal episodes were examined. Out of them
      a risk group was identified by the results of clinical and instrumental studies
      for their transformation to epilepsy. The group required anticonvulsive therapy
      and case follow-up along with EEG monitoring.

PMID- 8154216
TI  - [Acupuncture reflexotherapy of neurogenic bladder dysfunction in children with
      enuresis].
AB  - The urodynamics of the lower urinary tract was evaluated in 25 children treated
      for enuresis. The unstable bladder was observed in 16 patients. Twelve children
      with detrusor hyperreflexia comprised the largest group. Acupuncture was
      beneficial in 17 cases. The follow-up showed its detrusor-stabilizing effects in
      patients with neurogenic bladder dysfunctions. The success of the therapy is
      depended on the patients' mental and emotional status, concurrent abnormalities
      and accuracy in observing the practitioner's recommendations. The mechanisms of
      therapeutic effects of acupuncture are also discussed.

PMID- 8154217
TI  - [The use of the transcranial micropolarization method for decreasing the
      manifestations of hyperkinesis in patients with infantile cerebral palsy].
AB  - Transcranial micropolarization was used in the treatment of children with
      hyperkinetic form of infantile cerebral paralysis. The method was found to be
      more effective than various stereotaxic interventions on the brain or routine
      physiotherapy. Transcranial micropolarization exposure resulted in alleviation of
      hyperkinesis, posture-tonic reflexes, in improvement of active movements of the
      joints, supporting system, etc. Clinical status of patients exposed to this
      treatment modality improved by six times as against those treated traditionally.
      Clinical data and data of stimulation electromyography permit us to suggest a
      possible effect of transcranial micropolarization on the function of cerebral
      subcortical structures in patients with hyperkinetic form of infantile cerebral
      paralysis.

PMID- 8154218
TI  - [Changes in the excitability of the spinal motor neurons during sessions of
      functional biocontrol in patients with different forms of infantile cerebral
      palsy].
AB  - Excitability changes at the segmentary level of the spine were examined during
      functional bioregulation sessions administered to patients with various forms of
      infantile cerebral paralysis (spastic diplegia, spastic hemiparesis) by recording
      N- and M-responses of musculus soleus and musculus gastrocnemius medial head.
      Neurophysiologic disorders were revealed at the spinal level depending on the
      disease form. The authors suppose that presynaptic inhibition is to a greater
      measure impaired in spastic hemiparesis, whereas spastic diplegia is associated
      with more extensive involvement even of spinal inhibitory mechanisms proper.
      Sessions of functional bioregulation resulted in clinical improvement and in
      development of a trend to normalization of spinal reflectory excitability. Such
      changes were recorded in musculus soleus of children with spastic diplegia and in
      gastrocnemius muscle median head of those with spastic hemiparesis. Possible
      effects of directed afferent currents on structure and function of supraspinal
      systems regulating spinal mechanisms activity are discussed.

PMID- 8154219
TI  - [Histocompatibility antigens and their role in the pathogenesis of developmental
      anomalies of the nervous system in children].
AB  - Clinical and immunogenetic examinations of 40 patients with congenital diseases
      of the nervous system and of 10 couples of their parents revealed an association
      with HLA B12 antigen, HLA homozygosis in the majority of parents and children,
      and a high level of antigenic stimulation. The results may be considered as
      markers and criteria of a high risk of development of this disease in children.

PMID- 8154220
TI  - [The cerebrospinal fluid pathways in infantile cerebral palsy].
AB  - Liquor routes of the brain and spine were examined in 16 children aged 2 to 12
      with infantile cerebral paralysis by radioisotope cistern-myelography with Tc99m
      DTPK. Simultaneous imaging of liquor tract pathology in the brain and spine
      helped distinguish three variants of liquorodynamic abnormalities in infantile
      cerebral paralysis characterized by various combinations of disorders, in CSF
      circulation, resorption, and formation of routes for additional CSF discharge.
      The role of CSF routes involvement in the brain and spine in the formation of a
      pathologic pattern in infantile cerebral paralysis is analyzed.

PMID- 8154221
TI  - [Cerebrospinal fluid studies in acute lymphoblastic leukemia and lymphosarcomas
      in children].
AB  - The author presents data of cerebrospinal fluid (CSF) examinations in children
      with acute lymphoblastic leukemia and lymphosarcomas. CSF syndromes are described
      which permit a conclusion on increased permeability of the hematoencephalic
      barrier in this patient population. CSF changes polymorphism, cyclic pattern are
      demonstrated, as is a functional specificity of the hematoencephalic barrier in
      acute lymphoblastic leukemia and lymphosarcomas consisting in a trend to CSF
      normalization. The author claims that CSF remissions may occur which do not
      coincide with findings of clinical and morphologic examinations of the CNS in
      children with hemoblastoses.

PMID- 8154222
TI  - [The histochemical characteristics of the capillary bed of the brain in exposure
      to low-intensity laser radiation].
AB  - Rat brain was exposed to He-Ne laser at wavelength 632.8 nm, power density 0.76
      mWt/cm2. Hippocampal capillaries detected by alkaline phosphatase were examined
      in various periods (from 1 sec to 3 h) after the exposure. Changes of the enzyme
      activity in capillary walls, capillary length and diameter were examined after
      laser exposures of various duration. Enzymic activity and total capillary length
      were found to increase within the first 15 min of irradiation by 1.5-2 times. A
      longer irradiation resulted in reduction of these parameters. Capillary diameter
      changed negligibly after 15-min exposure, and after a longer irradiation a stable
      dilatation of capillaries was observed.

PMID- 8154223
TI  - [Intraventricular brain pressure in newborn infants with asphyxia and the means
      for its correction].
AB  - The paper deals with the information noninvasive tool of echoencephalographic
      determination of cerebral intraventricular pressure in the newborns. With this
      mode, spinal fluid pressures were measured in 80 patients with prior degrees II
      and III asphyxia and in 25 healthy children in the early neonatal period. To
      enhance the efficiency of treating the fluid-hypertensive syndrome in the
      newborns with hypoxically afflicted central nervous system, an atraumatic method
      of reflex therapy, including superficial acupuncture, metallic plate acupuncture
      and application has been developed and proposed if chemotherapeutical loads are
      restricted. Recommendations to choose acupuncture points are given and the
      advantages of the method are analyzed.

PMID- 8154224
TI  - [The level of neuropsychic development in young children and the potentials for
      their adaptation in an organized collective].

PMID- 8154225
TI  - [The clinical and sociodemographic characteristics of alcoholism patients who
      have committed illegal acts].
AB  - Clinical and statistical surveys of 330 patients with alcoholism who made illegal
      acts when they were alcohol-intoxicated have revealed that there is a
      relationship of the frequency and degree of illegal acts with clinical
      progressive features of a diseases and sociodemographic characteristics of
      patients and defined organizational measures for their prevention. The most
      severe illegal acts are made by patients with Stage II alcoholism with a
      progressive course and a short disease duration. The changed pattern of
      intoxication with its involvement into the clinical picture of epileptoidicity
      phenomena increases risks for them to make illegal acts. There is a relationship
      between the making criminogenic acts by alcoholics and their age, education
      level, social activity, and marital status. A risk group as to illegal acts has
      been identified among alcoholic patients.

PMID- 8154226
TI  - [The husbands of alcoholic women: experience in studying the psychopathology].
AB  - The familial and personal histories and present status of 41 married couples with
      the family pattern wherein the wife was alcoholic and the husband was non
      alcoholic were clinically studied. The purpose was to study the incidence and
      nature of psychopathological disorders in males in this marriage. It was found
      that 8 males who were divorced and had been married to an alcoholic female showed
      no mental disorders at the moment of the study. The remaining 33 husbands living
      with their alcoholic wife had borderline mental disorders. The diagnostic
      assessment of the detected disorders was the following in order of decreasing:
      neuroses, psychopathies, neurotic development of a personality. The high
      incidence rates of borderline psychopathological disorders in the husbands of
      alcoholic females suggest that aid should be rendered to the whole family rather
      than an alcoholic alone.

PMID- 8154227
TI  - [The spatial synchronization of cortical bioelectrical activity in different
      degrees of severity of alcohol dependence].
AB  - Stage-II alcoholics were examined 1-2 weeks after drinking periods, as were
      alcoholics during remissions lasting for 0.5 to 6 years. EEG was recorded by 10
      symmetrical leads: prefrontal, central, motor, sincipital, and temporal. Analysis
      of EEG correlations revealed reliable differences between the two groups in the
      total level of synchronism of cortical biopotentials, in activities of different
      regions, and in time course of relationships of various areas during
      hyperventilation and without it. The data may be used as objective criteria in
      assessment of the degree of a pathologic process in the CNS and for
      differentiating the patients by this sign for further differentiated therapy.

PMID- 8154228
TI  - [The characteristics of the changes in the blood enzyme activity of patients with
      acute alcoholic psychoses].
AB  - The serum activity of alanine aminotransferase, aspartate aminotransferase,
      glutamate dehydrogenase, gamma-glutamyl transferase and creatinine kinase was
      studied in 81 patients with chronic alcoholism and 31 patients with alcoholic
      psychoses. Eighty-one healthy apparently non-drinkers served as a control group.
      It is concluded that when acute alcoholic psychoses develop, patients with
      chronic alcoholism display a simultaneous increase in the activity of enzymes
      releasing from damaged muscular and hepatic tissues. This makes the application
      of a number of the diagnostic criteria developed in classical clinical enzymology
      impossible. The phenomenon of concurrent increases in the activity of creatine
      kinase, aspartate aminotransferase and glutamate dehydrogenase by 4 times or more
      has been proposed to be used as a criteria for identifying alcoholic psychosis in
      alcoholics.

PMID- 8154229
TI  - [The clinical course of schizophrenia with depersonalization disorders].

PMID- 8154230
TI  - [The role of the caudate nucleus in the neurophysiological mechanisms of the
      development of experimental alcoholism and concomitant extrapyramidal disorders].
AB  - Contribution of relationships between caudate nucleus and hippocampus,
      hypothalamus, amygdaloid, septum (with limbic brain emotiogenic mechanisms
      substrate), and neocorticoreticular mechanisms to the formation of experimental
      alcoholism was studied in rats. These relationships varied depending on
      alcoholization periods. Caudate nucleus was found to participate in mechanisms of
      regulation of dreamy states and sleep, as well as of quieting at early stages of
      alcoholization, this may be one of neurophysiologic mechanisms of development of
      craving to alcohol. The authors believe that transfer of the studied structures'
      functioning to a pathologic level at the stage of alcoholism formation may be
      regarded as a coarse destruction of restraining (caudate) mechanisms of
      reticulolimbic brain structures involving convulsive, emotional, and hyperkinetic
      disturbances and impairment of sleep-awakening processes.

PMID- 8154231
TI  - [A clinico-epidemiological analysis of Huntington's chorea in the population of
      Astrakhan].

PMID- 8154232
TI  - [The results of a study of speech disorders in schizophrenic patients using one
      of the variants of the projective method].
AB  - The study of speech disorders in schizophrenics led the authors to the conclusion
      that defects in speech and thinking activity in them are related to the sphere of
      communicative competence and interpersonality cooperation. Psycholinguistic
      methods of such defects investigation is proposed. A relationship was found
      between the type of schizophrenia course and the patient's response to speech
      stimulus. Strangeness of schizophrenics speech results from directive
      abnormalities, i. e. from the patients' rigidity to self-expression.

PMID- 8154233
TI  - [The Prader-Willi syndrome].

PMID- 8154234
TI  - [The differentiation of the pathogenetic variants of nerve trunk lesions].
AB  - There are two major variants of nerve trunk disease progression: demyelinating
      and axonal-axial. The authors have developed a significant and rapid diagnostic
      procedure to differentiate the type of nerve trunk affection based on
      simultaneous assessment of two parameters (immunological and
      electroneuromyographic) carrying out correlations between them. The immunological
      investigation included measurement of the serum autoantibodies to
      galactocerebrosides titer.

PMID- 8154235
TI  - [Expression of interferon alpha receptors in cell lines from human tumors.
      Relationship with the antiproliferative effect].
AB  - Alpha Interferon (IFN) membrane receptor expression was studied in four human
      tumor cell lines from several origins: Burkitt's lymphoma (Daudi cells), cervix
      adenocarcinoma (HeLa cells), larynx carcinoma (HEp-2 cells) and a grade III-IV
      glioblastoma (GL-5 cells). The number of receptors per cell expressed in each
      case did not correlate with the sensitivity of the cytostatic effect of IFN alpha
      2b. However, the Scatchard analysis of the affinity of the IFN-receptor complex
      did correlate with this effect. Daudi cells, which expressed 1927 receptors/cells
      with a high affinity (Kd = 3.30 x 10(-10) M) were the most sensitive to the
      antiproliferative effect. Growth inhibition was 30% with only 1.6pg/ml of IFN.
      HeLa cells expressed a mixture of high (Kd = 3.36 x 10(-10) M) and low (Kd = 3.21
      x 10(-9) M) affinity binding sites and were also sensitive to the
      antiproliferative effect but less than Daudi. HEp-2 and GL-5 cells, on the
      contrary, were very little sensitive to the antiproliferative effect of IFN and
      only expressed low affinity binding sites (Kd = 1.20 x 10(-8) M and Kd = 8.33 x
      10(-9) M) respectively. On the other hand, IFN alpha-2b binding assays to
      peripheral blood lymphocytes from 8 healthy individuals were also carried out as
      normal cells for comparison. The values obtained were 433 +/- 166 receptors per
      cell and Kd = 3.68 2.66 x 10(-10) M.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154236
TI  - Much ado about something: a commitment to public safety (with apologies to
      William Shakespeare).

PMID- 8154237
TI  - NCAST: an effective nursing tool for assessing family interaction.

PMID- 8154238
TI  - Ethics in the workplace: is ethics a luxury?

PMID- 8154239
TI  - A home care teaching tool. Care of an indwelling catheter at home.

PMID- 8154240
TI  - The noise you just heard was a paradigm shifting: regulation of the nursing
      profession in Alberta--Part two.

PMID- 8154241
TI  - Health Information: Nursing Components: a means to capture nursing's contribution
      to the health of Albertans.

PMID- 8154242
TI  - Lawsuits and nurses.

PMID- 8154243
TI  - Visual field prognosis in early glaucoma. A long-term clinical follow-up.
AB  - Fifty-four eyes of 45 patients with ocular hypertension developed early
      glaucomatous optic disc or visual field changes after a mean follow-up of 5.1
      years without therapy. These changes initiated antiglaucomatous treatment, and
      the eyes have been followed further on therapy for 2-14 years (mean 8.0 years) in
      a retrospective study. The mean intraocular pressure (IOP) was lowered from 28.9
      to 19.3 mmHg. Half of the eyes were still without field defects at the end of the
      study, whereas 7 eyes developed extensive field damage noticeable to the
      patients. The eyes with deteriorating visual fields could not be differentiated
      from the stable ones by means of the pre-therapy IOP, nor the mean or peak IOP on
      treatment. There was an accumulation of topical and general risk factors in the
      progressive eyes. The results support the importance of taking other risk factors
      than the IOP into consideration in the management of our glaucoma patients.

PMID- 8154244
TI  - Primary angle closure glaucoma and retinitis pigmentosa.
AB  - The prevalence of primary open angle glaucoma in patients with retinitis
      pigmentosa ranges from 2-12%. To the best of our knowledge the prevalence of
      primary angle closure glaucoma in retinitis pigmentosa patients has not been
      reported. This study was conducted to determine the prevalence of primary angle
      closure glaucoma in patients with retinitis pigmentosa and the relationship
      between the two. We reviewed 538 retinitis pigmentosa patients' charts seen
      between 1974-1987, in the Ocular Genetic Clinic in the Hospital of Sick Children,
      Toronto, Canada. The prevalence of primary angle closure glaucoma in our
      retinitis pigmentosa patients over 40 was 1.03%. We also reviewed three patients
      with primary angle closure glaucoma and retinitis pigmentosa. One patient had
      typical bilateral retinitis pigmentosa, one patient had bilateral sector
      retinitis pigmentosa, and one patient had unilateral retinitis pigmentosa and
      primary angle closure glaucoma in the same eye. Our data indicate that there is a
      strong association between retinitis pigmentosa and primary angle closure
      glaucoma.

PMID- 8154245
TI  - Postoperative prognostic indicators following trabeculectomy.
AB  - We evaluated prognostic indicators for long-term filtration from the ocular
      examination within the first three months following primary trabeculectomy
      without antimetabolite therapy. We found that in patients who were more easily
      controlled at one year postoperatively (intraocular pressure < or = 16 mmHg and
      using 0-2 medications), compared to those who were more difficult to control (>
      16 mmHg or on three medications), the intraocular pressure became significantly
      different between groups at three months and the number of glaucoma medications
      at eight weeks postoperatively. More easily controlled patients had greater bleb
      elevation by one month and extent of bleb formation at two weeks postoperatively.
      The presence of microcysts, anterior chamber depth, and avascularity did not
      differ between the two groups. This study suggests that differences in the ocular
      examination exist within the first three months following trabeculectomy which
      reflect the postoperative intraocular pressure control at one year.

PMID- 8154246
TI  - Intra-operative use of 5-fluorouracil in glaucoma filtering surgery.
AB  - This study reviews the outcome of 14 eyes considered to be at risk of surgical
      failure undergoing trabeculectomy with 5-Fluorouracil (5-FU). The antimetabolite
      was administered intra-operatively by placing a surgical sponge soaked in 5-FU
      (25 mg/ml) directly on the sclera under the conjunctival flap for 5 minutes. All
      eyes showed a reduction in intraocular pressure (IOP) at a mean follow-up of 18.5
      weeks, and only one eye required topical antiglaucoma medication. Mean IOP
      reduction at final follow-up was 43.1%. No eyes showed any corneal problems
      associated with the intra-operative use of 5-FU. These results suggest that the
      intra-operative use of 5-Fluorouracil is an effective way of improving surgical
      success in at risk eyes. The early complications appear to be less than those
      associated with post-operative subconjunctival injections of 5-FU, but the long
      term differences are still to be shown.

PMID- 8154247
TI  - The comparative analysis of optic disc damage in exfoliative glaucoma.
AB  - To compare the initial and follow-up discernible glaucomatous neuroretinal rim
      (NRR) and parapapillary chorioretinal changes in patients with primary open-angle
      glaucoma (POAG) and exfoliative glaucoma (EG), we analyzed 40 optic discs from 40
      patients with POAG, 40 optic discs from 40 patients with EG and 20 optic discs
      from 20 normal subjects. The mean intraocular pressure was higher in the EG group
      when compared with POAG (p < 0.001). Although the mean disc areas in both groups
      were not significantly different, the mean initial NRR area to disc area ratio
      was significantly smaller in patients with EG (p < 0.001). At the initial
      diagnosis the most prominent NRR defects of the patients with POAG were at the
      inferotemporal and superotemporal sectors, followed by the temporal and nasal
      sectors. However, the NRR in the EG group was noticed to decrease diffusely
      without such a sectorial preference. There was no significant difference between
      the mean loss of the NRR to disc area ratio in both groups at the end of the
      follow-up period of 1 year (p > 0.05). The values of parapapillary chorioretinal
      atrophy areas in POAG and EG patients were not significantly different from each
      other, neither at the initial examination nor during the follow-up period (p >
      0.05). Those results suggest that high intraocular pressure in eyes with EG may
      constitute a major risk for rapid and progressive glaucomatous optic disc damage.

PMID- 8154248
TI  - Morphology of iris vasculopathy in exfoliation glaucoma.
AB  - Iris tissue obtained from 26 consecutive patients operated upon for exfoliation
      glaucoma and control iris tissue from 26 age-matched subjects operated upon for
      primary open angle glaucoma was used to investigate the iris vasculopathy
      associated with exfoliation glaucoma. By light microscopy exfoliation material
      was discerned by increased density of the perivascular matrix in affected
      vessels. By transmission electron microscopy exfoliation vasculopathy was divided
      into 4 grades. Grade I was characterized by focal accumulation of exfoliation
      material without evidence of cellular degeneration. In grade II, exfoliation
      material accumulation was accompanied by degeneration of vascular supporting
      cells; endothelial cells were unaffected. In grade III, endothelial cells
      exhibited degenerative changes and in grade IV, exfoliation material occupied an
      acellular vascular wall (ghost vessel). It is suggested that in iris vessels the
      synthesis of exfoliation material can be attributed primarily to the vascular
      supporting cells.

PMID- 8154249
TI  - Acute effect of topical carteolol on ocular pulsatile volume change.
AB  - To determine whether topical carteolol affects ocular blood flow, we studied
      effects of carteolol 2% on the ocular pulse waves in 9 normal volunteers, and
      analyzed the results as variations in pulsatile volume changes (PVC) for one
      minute (PVCm) using the Friedenwald's pressure-volume relationship. PVC means a
      volume for the pressure amplitude in each pulse. The pulse waves were recorded
      with a pneumatonometer and analyzed by a computer. The PVCm change 15 min after
      the carteolol instillation was evaluated with the control performed with
      biological salt solution in the same manner. The data showed a net increase in
      the PVCm of the carteolol-instilled eyes (21.3 +/- 6.4 microliters/min: mean +/-
      standard error, p < 0.05, paired t-test). Considering a finding that PVCm takes
      50% of the total ocular blood flow, the results suggest a possible alteration in
      the total flow by a carteolol instillation.

PMID- 8154250
TI  - Pseudoexfoliation syndrome and extracapsular cataract extraction.
AB  - Extracapsular cataract extraction (ECCE) in 139 eyes with pseudoexfoliation
      syndrome was compared to 762 eyes without pseudoexfoliation syndrome in a
      consecutive study. Preoperative findings, operative procedure and problems were
      registered, stored and analyzed in a computer program package. Of the patients
      with pseudoexfoliation syndrome 88.5% were 70 years or older, compared to 67.2%
      of the patients without pseudoexfoliation syndrome (p < 0.001). Glaucoma occurred
      in 48.9% of eyes with pseudoexfoliation syndrome and in 6.8% of eyes without
      pseudoexfoliation syndrome, respectively. Poorly dilated pupil was demonstrated
      in 46.8% and in 5.8% of eyes with and without pseudoexfoliation syndrome,
      respectively. Capsule/zonulae tears (without vitreous loss) occurred in 4.3% of
      the pseudoexfoliation syndrome eyes, compared to 1.3% in eyes without
      pseudoexfoliation syndrome (p < 0.05). The incidence of vitreous loss was similar
      in both groups. We found no correlation between the pupil size and
      capsule/zonulae tears or vitreous loss in either group. In conclusion, when
      appropriate care is undertaken, ECCE with posterior chamber IOL implantation is a
      safe procedure in pseudoexfoliation syndrome eyes.

PMID- 8154251
TI  - Results and complications after extracapsular cataract extraction in eyes with
      pseudoexfoliation syndrome.
AB  - Postoperative results and complications in 136 eyes with pseudoexfoliation
      syndrome were compared to 744 eyes without pseudoexfoliation syndrome in a
      consecutive study. The patients were followed for 4 months postoperatively.
      Excluding cases with glaucoma, 81.4% of the pseudoexfoliation eyes and 83.0% of
      the eyes without pseudoexfoliation achieved a corrected visual acuity of 5/8.5 or
      better. IOL malposition was rare in both groups (1.5% in the pseudoexfoliation
      group and 1.6% in the group without pseudoexfoliation). IOP elevation the first
      day postoperatively occurred most often in the pseudoexfoliation eyes. In the
      pseudoexfoliation eyes, postoperative iritis and cellular precipitates were
      demonstrated in 16.2% and 11.0%, respectively, compared to 3.8% and 3.2% in the
      eyes without pseudoexfoliation (p < 0.001). The frequency of an inflammatory
      reaction was highly correlated to small pupil size during operation in both
      groups.

PMID- 8154252
TI  - Development of cataract after trabeculectomy.
AB  - Cataract progression after trabeculectomy was investigated in a study of 47 eyes
      with exfoliative glaucoma (ExG) and in 20 eyes with primary open-angle glaucoma
      (POAG). Cataract progression was assessed from the need for cataract extraction,
      deterioration of visual acuity by > or = 2 Snellen lines, myopic change in the
      refraction and increase in the lens opacity value, measured with a Lens Opacity
      Meter 701. Measurements were made 6 and 12 months after trabeculectomy and at the
      follow-up visit at 26 +/- 11 months. ExG, age, hypotony (IOP < or = 5 mm Hg)
      lasting > or = 5 days and early postoperative IOP rise > 30 mm Hg were observed
      to be risk factors for cataract progression. In pairwise analysis of 14 patients,
      in which the unoperated eye served as the control, a myopic change of refraction
      was the most frequent indicator for a change in the structures of anterior
      segment, possibly indicating cataract progression.

PMID- 8154253
TI  - Retinal detachment following intracapsular and extracapsular cataract extraction.
      A comparative, retrospective follow-up study.
AB  - In a retrospective study we reviewed the post-operative incidence of retinal
      detachment in a consecutive series of 762 eyes operated on with intracapsular
      cataract extraction and a consecutive series of 1351 eyes operated on with
      extracapsular cataract extraction. Follow-up time was 2 1/2-4 1/2 years in both
      series. The incidence of retinal detachment was 0.79% after intracapsular
      cataract extraction and 0.44% after extracapsular cataract extraction. The
      difference was not statistically significant. Age below 70 years was not
      statistically significantly correlated to retinal detachment.

PMID- 8154254
TI  - Retrobulbar anaesthesia. A clinical evaluation of four different anaesthetic
      mixtures.
AB  - One-hundred and thirty-nine consecutive cases of retrobulbar blocks were
      evaluated concerning clinical effect on motility and pain. The patients were
      randomly selected to one of four different mixtures of anaesthetics. A mixture
      containing lidocaine w/adrenaline, bupivacaine w/adrenaline and hyaluronidase was
      shown to be significantly more effective than any of the other tested mixtures
      concerning analgesia and significantly better than mixtures without hyaluronidase
      concerning motility/akinesia.

PMID- 8154255
TI  - Retrobulbar anesthesia with and without hyaluronidase in extracapsular cataract
      surgery. A prospective, randomized, double-blind study.
AB  - Eighty patients with senile cataract were subjected to a planned extracapsular
      cataract extraction (ECCE) with implantation of a posterior chamber intraocular
      lens. Retrobulbar anesthesia was administered by injection of 4 mg lidocaine 2%
      with adrenalin. In 40 patients 150 I.U. hyaluronidase (Kinetin) was added to the
      anesthesia. The hyaluronidase group had a significantly lower frequency of iris
      prolapse, and deeper anterior chamber, both before and after expression of the
      lens nucleus. Possible mechanisms explaining the beneficial effect of
      hyaluronidase in extracapsular cataract surgery are discussed.

PMID- 8154256
TI  - Evaluation of a flexible one-piece open-loop anterior chamber lens 'Symflex 350B'
      3-4 years after implantation.
AB  - One-piece, open-loop flexible anterior chamber lens, Symflex 350B, was implanted
      in 90 eyes, 26 after extracapsular cataract extraction (ECCE), and 57 after
      intracapsular cataract extraction (ICCE), and in 7 cases the operation was done
      as a secondary implantation. The cohort was followed 3.4-4.4 years, 68 eyes were
      included in the last examination. At the final examination 7 eyes (10.29%) had
      developed corneal oedema. 6 eyes had undergone ICCE and one eye had been
      secondarily implanted. In no case was vaulting or malposition of the intraocular
      lens (IOL) found. The decompensation appeared shortly after the operation in 2
      cases, one case being a secondary implantation between 1 year and 3-4 years after
      implantation. All extracapsularly operated eyes showed normal corneas, but the
      difference was not statistically significant. Neither ovalling of the pupils, nor
      tissue growth over the haptic feet in the anterior chamber angle, nor the visual
      acuity (VA) changed significantly from the 1-year to the 3-4-years examination.
      The intraocular pressure (IOP), however, was statistically significantly lowered
      3-4 years postoperatively.

PMID- 8154257
TI  - Prevalence and risk factors of retinopathy in children with diabetes. A
      population-based study on Finnish children.
AB  - The prevalence of retinopathy in children with insulin-dependent diabetes
      mellitus (IDDM) was studied in a population-based survey on 194 of the 216
      subjects (89.8%) with IDDM aged 4.6 to 16.6 years living in the county of Oulu,
      Finland. The diagnosis of retinopathy was based on fundus photography. The median
      age of the children was 12.2 years and the median duration of diabetes 4.5 years
      (range 0.14.2 years). Retinopathy was found in 21 (10.8%) of cases. All of the
      changes seen were mild and did not require treatment. All the children with
      retinopathy were pubertal or postpubertal, and an association was found between
      the presence of retinopathy and the long-term diabetes control, duration of
      diabetes, age and albuminuria. Logistic regression analysis showed increasing
      duration of diabetes, puberty and elevated blood glycated haemoglobin to be the
      main risk factors explaining the occurrence of retinopathy. In patients aged 13
      16 years retinopathy was also related to female sex and diastolic blood pressure,
      but in logistic regression analysis duration of diabetes and glycated haemoglobin
      were the best predictors.

PMID- 8154258
TI  - Measurement of visual readaptation time after flash exposure using optokinetic
      nystagmus.
AB  - It is concluded that measurement of visual readaptation time (RAT) using
      optokinetic nystagmus (OKN) is a repeatable measure of visual recovery after
      flash exposure. The semi-automatic method for measurement of RAT used here
      requires further development, but it is anticipated that the improved method will
      provide an efficient tool for increased understanding of the physiology of flash
      blindness. In this study on humans, it was found that if RAT is recorded twice on
      the same occasion, the second RAT is shorter. However, there was no systematic
      difference between RAT recordings on consecutive occasions. The newly developed
      semi-automatic method was found to provide RATs comparable to those obtained by
      manual measurement on a paper print out of EOG recordings. In RAT estimation, the
      variability between subjects shadows other sources of random variability. The
      least number of subjects needed in each group to detect a 20% alteration of RAT
      due to an experimental factor (alpha = 0.05, beta = 0.05) was estimated to 13
      with independent groups design. For paired design < 10 are needed. OKN was
      elicited with a horizontally moving vertical grating. The eye movement was
      recorded by DC EOG. A sudden flash of green light temporarily abolished the OKN.
      The internal between the flash and the reappearance of OKN was measured as the
      RAT.

PMID- 8154259
TI  - Dark focus of accommodation in children with accommodative esotropia and
      hyperopic anisometropia.
AB  - We evaluated the dark focus of accommodation, referred to as tonic accommodation,
      in 60 young hyperopic subjects, 20 with and 20 without accommodative esotropia,
      and 20 with hyperopic anisometropia. We measured the distance, dark, and
      cycloplegic refractive errors by the Nidek Autorefractometer AR1600. The
      difference between dark and cycloplegic refractive errors was defined as the dark
      focus. The dark focus was significantly larger in esotropic eyes than in non
      esotropic eyes, despite similar cycloplegic refractive errors in both types of
      eyes, suggesting that tonic accommodation may be associated with ocular position.
      The dark focus was similar in eyes of the same subjects with hyperopic
      anisometropia and also in normal and amblyopic eyes, suggesting that tonic
      accommodation is similar in both eyes in subjects with anisometropia and
      amblyopia.

PMID- 8154260
TI  - The influence of vitamins and trace element supplements on the stability of the
      pre-corneal tear film.
AB  - The tear stability af 60 normal healthy subjects was measured and repeated 10
      days later. Using a double-blind protocol, during the interim period 2/3 of the
      subjects (the treatment groups) took a commercially available daily dietary
      supplement and the remaining 1/3 acted as controls. The recommended daily dose
      was applied to the treatment groups. 20 of the treatment group took a daily
      dietary supplement of a mixture consisting of vitamins (e.g. A, B1, B2, B6, E)
      and trace elements (e.g. calcium iron, manganese), the other 20 took purely
      vitamin C tablets. The tear stability of both treated groups increased, however,
      the multi-vitamin and trace element group demonstrated the more consistent and
      individually predictable improvement. Within this group, the characteristics of
      the regression line correlating the initial mean (x) and final mean (y) tear
      stabilities were, y = 5.94 + 1.02x. The tear stability of the control group
      individuals did not significantly change.

PMID- 8154261
TI  - Nebulae at keratoconus--the result after excimer laser removal.
AB  - Ten patients underwent excimer laser ablation due to nebula formation at
      keratoconus. The nebulae interfered significantly with contact lens fit or
      wearing time. The mean follow-up time in these patients was 16.5 months.
      Following surgery all patients could be successfully fitted with a contact lens
      and thereby obtain good visual acuity. Furthermore, contact lens wearing time was
      8 hours or more in all cases. In 2 patients the nebulae recurred but were
      successfully retreated.

PMID- 8154262
TI  - Serum sialic acid levels in patients with sympathetic ophthalmitis.
AB  - Serum sialic acid levels were measured in 16 patients with sympathetic
      ophthalmitis, 36 with neglected traumatic uveitis following penetrating injury
      and 40 healthy subjects. There was no significant alteration of its level in
      patients with traumatic uveitis. However, its level was significantly elevated in
      patients with sympathetic ophthalmitis. It was high even in the early stage of
      the disease. It decreased significantly at the remission stage. It is proposed
      that measurement of sialic acid level in serum can be used as a diagnostic aid
      when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical
      grounds. The extent of rise in its level may be considered a good parameter of
      the degree of severity of sympathetic ophthalmitis. It may also act as a useful
      tool to evaluate the drug efficacy in this disease.

PMID- 8154263
TI  - Efficacy and retention time of a new tear substitute.
AB  - The tear substitute Lacrozym has been compared with Tears Naturale in a double
      blind study. Baseline tear film break-up time, efficiency by determining the
      maximum of the break-up time values after tear substitute administration, and
      retention time has been established. A similar increase of break-up time values
      were found after 10, 15, 20 and 30 min administration of Lacrozym and Tears
      Naturale, respectively. Retention times of both tear substitutes were found to be
      about two hours, more exactly 110 and 120 min for Lacrozym and Tears Naturale,
      respectively.

PMID- 8154264
TI  - Conjunctival amyloidosis: is it related to trachoma?
AB  - Due to presence of trachoma in a large percentage of cases of conjunctival
      amyloidosis, trachoma has been blamed for causing secondary localized
      amyloidosis. However, there is no study to demonstrate evidence of amyloidosis in
      tarsoconjunctival specimens of trachomatous lids. 50 eyes of 35 patients having
      trachomatous eyelids with thickened tarsal plate, trichiasis and entropion had a
      tarsoconjunctival biopsy (3 mm x 20 mm) from the upper lid. Histopathological
      examination using Haematoxylin--eosin and congo red stains failed to reveal
      evidence of amyloid deposition in any of the biopsies. This is the first
      histopathological study of amyloidosis in trachomatous patients. Our study rules
      out the long-standing concept of trachoma having causal relationship with
      conjunctival amyloidosis. It is concluded that conjunctival amyloidosis occurring
      in trachomatous lids should be considered as primary localized amyloidosis.

PMID- 8154265
TI  - PUVA treatment and choroidal malignant melanoma.
AB  - Choroidal malign melanoma showing rapid progression in a boy 17 years old is
      presented. The patient was under therapy with methoxy psoralen + Ultraviolet A
      (PUVA)* for psoriasis vulgaris. He had undergone complete ophthalmologic
      examinations with three-month intervals from the beginning of this therapy. The
      tumor was detected in the seventh month, rapidly enlarging within the next twenty
      days, and eventually leading to enucleation. PUVA is known to be a risk factor
      for cutaneous malign melanoma. However, there is no reported incidence of
      choroidal malign melanoma in PUVA treated patients. To our knowledge, this is the
      only case showing the possible role of PUVA therapy as a predisposing factor in
      the development of uveal malign melanoma.

PMID- 8154267
TI  - Wegener's granulomatosis with rapidly progressive retinitis and anterior uveitis.
AB  - A case of a Wegener's granulomatosis with severe retinitis and anterior uveitis
      is presented. The diagnosis of Wegener's granulomatosis was based on the clinical
      features and on histologic findings of multiple lesions. Anterior uveitis and
      severe retinitis developed in both eyes, resulting in decreased visual acuity.
      This case indicates that thorough examinations of the ocular fundus should be
      performed routinely during the follow-up of patients with Wegener's
      granulomatosis.

PMID- 8154266
TI  - Co-existence of exfoliation syndrome, previous iris surgery, and heterochromia.
AB  - A case is described where exfoliation syndrome developed in a relatively young
      patient with heterochromia. The patient had previously undergone large radial
      iridotomies as part of penetrating keratoplasty procedures. This case illustrates
      an association between iris surgery and early manifestation of exfoliation
      syndrome.

PMID- 8154268
TI  - Acute frosted retinal periphlebitis.
AB  - A 30-year-old woman developed bilateral acute vision loss without any systemic
      symptoms. There was diffuse retinal edema and thick perivenous sheathing with
      moderate vitreous inflammation. Fluorescein angiography showed late staining and
      dye leakage from diseased vessels. Oral corticosteroid treatment stabilized the
      visual acuity and fundus of the left eye but did not halt the progression to
      total fibrosis in the right eye.

PMID- 8154269
TI  - Unilateral congenital fibrosis syndrome presenting with hypertropia.
AB  - A case of sporadic unilateral congenital fibrosis is described. The patient had
      the additional unusual features of primary position hypertropia and minimal
      ptosis.

PMID- 8154270
TI  - Early failures among 14,009 cemented and 1,326 uncemented prostheses for primary
      coxarthrosis. The Norwegian Arthroplasty Register, 1987-1992.
AB  - In the Norwegian Arthroplasty Register, 15,335 primary total hip replacements
      (THR) in patients with primary arthrosis were followed for 0-5.4 years. The
      Kaplan-Meier estimate of cumulative failure (revision) after 4.5 years was 2.7
      percent for cemented THR, compared to 6.5 percent for uncemented. In patients
      under 65 years the cumulative revisions for cemented and uncemented THR were 3.3
      and 7.9 percent. For the acetabular components, the cumulative failures were 0.6
      percent for cemented and 1.7 percent for uncemented, and for femoral components
      1.7 and 3.9 percent after 4.5 years. Adjusting for age and sex using a Cox
      regression model, 2 times higher rates of failure were found comparing uncemented
      to cemented THR. The results for uncemented prostheses were more unfavorable in
      young patients. In men and women under 60, the revision rates were increased 6
      and 3 times, respectively, for patients with uncemented THR compared to those
      with cemented THR. Restriction of the end-point to revision for aseptic loosening
      gave results similar to the over-all results. No difference between cemented and
      uncemented THR was seen for revisions due to infection, whereas the most
      unfavorable results for uncemented THR were seen when revisions due to causes
      other than infection and aseptic loosening were considered.

PMID- 8154271
TI  - Vascularized extensor digitorum brevis to reconstruct the Achilles tendon. A case
      report.

PMID- 8154272
TI  - Poor results after resection for Haglund's heel. Analysis of 35 heels in 23
      patients after 3 years.
AB  - We reviewed 23 patients 3 (1-6) years after resection of the calcaneus for 35
      Haglund's heels. 19 heels had been treated with a small resection and 16 with a
      large resection. The effect on the heel pain was independent of the size of the
      resection, but stiffness and ankle pain were more frequently associated with
      large than small resections. At follow-up persistent heel pain was found in 12
      heels and additional various late complaints in 22. The overall clinical outcome
      was good in 20 heels, satisfactory in 10 and poor in 5 heels.

PMID- 8154273
TI  - Osteochondral lesions of the talar dome in children. A 24 (7-36) year follow-up
      of 13 cases.
AB  - 13 patients who in childhood had had osteochondral lesions (OCL) of the talar
      dome participated in a long-term follow-up including physical examination,
      computed tomography (CT) and conventional radiographs. Most of the cases were
      caused by trauma. Conventional radiographs showed abnormal findings in 4 cases
      and CT in a further one. In 3 cases the primary lesion could still be seen as an
      osteochondral defect, and 2 had a loose body in the joint. 3 of these 5 patients
      had mild symptoms. We conclude that arthrosis following OCL in childhood is
      infrequent and recommend conservative treatment initially. In those with
      persisting symptoms, additional imaging evaluation with CT and MRI is
      recommended.

PMID- 8154274
TI  - Osteolysis and particle disease in hip replacement. A review.

PMID- 8154275
TI  - Decrease in vertebral bone density after hip arthroplasty. A quantitative
      computed tomography study in 18 arthrosis cases.
AB  - We investigated the bone mineral density (BMD) of the lumbar vertebrae L1-3 with
      quantitative computed tomography (QCT) in 18 patients who had been operated on
      with hip arthroplasty because of unilateral arthrosis. In an earlier prospective
      study, we did not find any bone mineral changes in the femur or tibia after hip
      arthroplasty in spite of a large increase of the thigh muscle mass as a sign of a
      remobilization after the operation. The median BMD had decreased 5.3-8.4 percent
      in all the measured vertebrae after 6 months postoperatively. Because of the
      patients' improved walking ability after the operation, this decrease in
      cancellous vertebral BMD is interpreted as a sign of a post-traumatic osteopenia.

PMID- 8154276
TI  - Autologous blood transfusion with recombinant erythropoietin treatment. 22
      arthroplasties for rheumatoid arthritis.
AB  - 12 anemic and 10 non-anemic patients with rheumatoid arthritis were treated with
      recombinant human erythropoietin (rHuEPO) before arthroplasty. The patients
      received 400-800 units/kg of rHuEPO subcutaneously once a week. Autologous blood
      was collected after the hemoglobin concentration was increased by 5 percent or
      more. All but one of the patients responded to the treatment. They were given 1-3
      units of autologous blood, and underwent the operation without homologous blood
      transfusion. The mean duration of the treatment was 1 month. In 1 patient with
      severe anemia, additional transfusion with 2 units of blood was necessary during
      the operation. In all patients, there was a tendency for the hemoglobin response
      ratio to rHuEPO to correlate negatively with the initial CRP levels. The
      treatment did not affect the patients' clinical rheumatologic condition and there
      were no adverse effects. These results demonstrated that the treatment with
      subcutaneous rHuEPO is both effective and non-toxic and can therefore eliminate
      the need for homologous blood transfusion in anemic patients undergoing
      arthroplasty for rheumatoid arthritis.

PMID- 8154277
TI  - Effects of polymerization heat and monomers from acrylic cement on canine bone.
AB  - We investigated the effects of polymerization heat and toxicity of
      polymethylmetacrylate bone cement in the canine tibial diaphysis. Heat was
      studied by filling the tibias with either bone cement or bone wax contained in a
      monomer tight membrane pouch. Toxicity was studied by filling both tibias with
      cement, with the control side contained in the membrane pouch. Bone blood
      perfusion was measured by microsphere technic, and bone remodeling by 99mTc
      methylene diphosphonate uptake and by histologic technique. In bone exposed to
      the combination of polymerization heat and monomer, both perfusion and remodeling
      were impaired. We did not find any effects of polymerization heat alone. We
      conclude that hot toxic chemicals from bone cement during polymerization may
      inhibit bone blood perfusion and remodeling, whereas heat alone seems to be of
      minor importance for the regenerative processes in cemented diaphyseal bone.

PMID- 8154278
TI  - Locking and compression of the lag screw in trochanteric fractures is not
      beneficial. A prospective, randomized study of 153 cases.
AB  - 153 patients with a trochanteric hip fracture were operated on with a compression
      hip screw (CHS) and followed for 4 months. They were randomized into 2 groups,
      with or without a key and compression of the lag screw. Greater sliding of the
      lag screw was noted in cases where the compression screw and the key were used,
      especially in women over 80 years of age and in patients with a previous fracture
      indicating osteoporotic bone. Use of a key and compression of the lag screw gave
      no advantage, and we do not recommend this for treatment of trochanteric hip
      fractures.

PMID- 8154279
TI  - Basic fibroblast growth factor increases allograft incorporation. Bone chamber
      study in rats.
AB  - We found increased penetration of new bone into a frozen bone allograft which had
      been pretreated with basic fibroblast growth factor (bFGF). Pairs of grafts were
      placed in newly designed titanium bone chambers implanted bilaterally in rat
      tibiae. The ingrowing bone can enter the cylindrical interior of the chamber only
      at one end. It then penetrates the graft inside the chamber but, due to the
      length of the cylinder, it never reaches the other end. The distance which the
      ingrown bone has reached into the graft can then be measured on histological
      slides. With bFGF there was a 51 percent increase in the bone penetration
      distance at 6 weeks in this model. It also appeared that further penetration had
      almost ceased in the controls, whereas in the bFGF-treated specimens, membranous
      ossification was still going on.

PMID- 8154280
TI  - Effects of graded reaming on fracture healing. Blood flow and healing studied in
      rat femurs.
AB  - In 30 rats, closed bilateral fractures of the femur were produced. On the left
      side intramedullary reaming was performed to 1.6 mm, and the fracture fixed-with
      a steel pin with a diameter of 1.6 mm. On the right side the femoral canal was
      reamed to 2.0 mm and a hollow steel tube with a diameter of 2.0 mm was used for
      fixation. An additional 8 rats were used to obtain mechanical, dimensional and
      flow data on intact femurs, and another 10 rats were used to study the acute flow
      changes caused by fracture and different degrees of reaming and fracture.
      Fracture and reaming reduced total bone and cortical bone blood flows to about
      one third of normal flow, with no differences between the 1.6-mm and the 2.0-mm
      reamed bones. At 4 weeks, total bone flow was about double and cortical bone flow
      about 4 times increased in the 1.6-mm group. In the 2.0-mm reamed bones increases
      of approximately 5 times in total bone flow and of about 7 times in cortical flow
      were found. Callus flow was about twice the size of the respective cortical flow
      in both groups. Both total and cortical flows gradually subsided, without
      differences between the 2 groups. At 12 weeks, the callus area in the 2.0-mm
      group was greater than in the 1.6-mm group, while bone dimensions were greater in
      the 2.0-mm group at 4 and 12 weeks. Bending moment and rigidity were greater in
      the 1.6-mm group than in the 2.0-mm one at every time interval; no differences
      were found in fracture energy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154281
TI  - Local injection of TGF-beta increases the strength of tibial fractures in the
      rat.
AB  - The effect of Transforming Growth Factor beta (TGF-beta) administered locally
      around the fracture line of healing rat tibial fractures was investigated after
      40 days of healing. TGF-beta in a dose of 4 ng or 40 ng was injected every second
      day during the healing period. The strength, stiffness, energy absorption and
      deflection of the fractures were measured in a materials-testing machine.
      Compared with placebo-treated animals, the ultimate load of the fractures
      increased in the group injected with 40 ng of TGF-beta, but not in those injected
      with 4 ng. TGF-beta induced a dose-dependent increase in the cross-sectional area
      of the callus and bone at the fracture line. Consequently, local treatment of
      fractures with TGF-beta increases the callus formation and strength. The energy
      absorption and deflection capacities of the healing fractures are preserved.

PMID- 8154282
TI  - Intercalary bone allografts. 23 tumor cases followed for 3 years.
AB  - From 1987 to 1991, 26 patients with malignant bone tumors (osteosarcoma, Ewing's
      sarcoma, chondrosarcoma and malignant fibrous histiocytoma) in the diaphysis or
      metaphysis of long bones have been treated by chemotherapy, radiotherapy and
      intercalary bone allograft replacement after resection. The mean follow-up was 3
      years in 23 patients, 2 died from tumors, and 1 had an amputation because of
      local recurrence. Allograft incorporation in 11 metaphyseal anastomoses was
      excellent in all cases. In the 23 diaphyseal anastomoses there were 6 non-unions.
      Other complications were deep infection in 3 cases, leg length discrepancy in 2
      and allograft fracture in 2. Function became satisfactory in 14 cases.

PMID- 8154283
TI  - Soft tissue sarcoma should be treated at a tumor center. A comparison of quality
      of surgery in 375 patients.
AB  - We analyzed the quality of surgery in a population-based series of 375 patients
      with primary soft tissue sarcoma of the extremity (n 329) and trunk wall (n 46).
      The quality was measured as the total number of operations performed for the
      primary tumor--biopsy, excision, reexcision--and the local recurrence rate. A
      comparison was made between patients referred to our tumor center before surgery
      (n 195), after surgery (n 102), and not referred for the primary tumor (n 78).
      The total number of operations for the primary tumor in patients not referred was
      1.4 times higher, and in patients referred after surgery 1.7 times higher than in
      patients referred before surgery. The local recurrence rate in patients not
      referred was 2.4 times higher, and in patients referred after surgery 1.3 times
      higher than in patients referred before surgery. Our findings show that patients
      with soft tissue sarcoma should be treated at a tumor center, and that they
      should be referred before surgery.

PMID- 8154284
TI  - Gait after knee arthroplasty for femoral tumor. Foot pressure patterns recorded
      in 20 patients.
AB  - We evaluated pressure distribution patterns under the feet during gait in 20
      patients after resection of malignant bone tumor and endoprosthetic replacement
      of the distal femur. In all cases, a modular cementless, hinged prosthesis had
      been used. The examination was performed after 4 (1-6) years. Shortened contact
      phase, decreased peak pressure, and reduced force-time integral during gait
      analysis were observed on the operated side. Peak pressure in the heel and the
      toe regions was decreased and the load (force-time integral) in the metatarsal
      heads and the big toe regions was reduced. There was a positive correlation
      between load under the foot and knee extension strength, measured isokinetically.

PMID- 8154285
TI  - Function following limb salvage for primary tumors of the shoulder girdle. 10
      patients followed 4 (1-11) years.
AB  - 10 patients with primary neoplasms of the shoulder girdle underwent limb salvage
      procedures involving resection of the proximal humerus and parts of the scapula
      and clavicle. The function of the ipsilateral limb was assessed in all patients,
      in 9 at least one and a half years after surgery. Function was good in 3 of the 6
      patients in whom an interposition bone graft was used and a successful shoulder
      arthrodesis was achieved. In the remaining 3, proximal arthrodesis was
      unsuccessful and the result was fair in 2 and a failure in 1. All 3 patients in
      whom the extended Tikhoff Linberg type of reconstruction was undertaken had good
      function although unsatisfactory cosmetic results. The 10th patient, who had a
      temporary cement and wire interposition, died of distant metastases 8 months
      after surgery and was considered a failure.

PMID- 8154286
TI  - Pain after use of the central third of the patellar tendon for cruciate ligament
      reconstruction. 33 patients followed 2-3 years.
AB  - We performed reconstruction of the anterior cruciate ligament in 33 patients
      using the central third of the patellar tendon. In 20 patients we did an
      arthroscopically-assisted procedure, while 13 patients had an additional mini
      arthrotomy through the gap in the patellar tendon. After 2-3 years the subjective
      knee function, according to the Lysholm score, was excellent or good in 18 knees
      and fair or poor in 15 knees, mainly due to anterior knee pain. Although 18
      patients complained about anterior knee pain, only 1 patient required further
      surgery. After the operation the patella had a lower position. A flexion
      contracture was found in 7 patients, and 13 had heterotopic bone formation at the
      apex of the patella. Although stability was restored in 31 of the 33
      reconstructed knees, anterior knee pain was a frequent complication. There were
      no correlations between the anterior knee pain and patellar height, flexion
      contracture or heterotopic bone formation.

PMID- 8154287
TI  - Through knee amputation with gastrocnemius musculocutaneous flap. 6 cases of
      tibial osteosarcoma followed for 3 (1-6) years.
AB  - 6 cases of proximal tibial osteosarcoma were operated on by through knee
      amputation using a long dorsal gastrocnemius musculocutaneous flap; the usual
      anterior flap could not be used because of tumor size and the location of the
      biopsy tract. The only complication was one wound dehiscence which healed. The
      stump was of good quality in all patients. At follow-up, the patients walked
      without walking aids.

PMID- 8154288
TI  - Revision of infected hip replacement. Two-stage procedure with a temporary
      gentamicin spacer.
AB  - We revised 5 infected totally-replaced hips in 2 stages. At the first operation a
      gentamicin-loaded modelled cement spacer was inserted, and the definitive
      prosthesis was inserted 3-8 weeks later. 9-24 months after the last operation,
      there was a recurrent infection in 1 case. 2 of the patients could walk in the
      interval.

PMID- 8154289
TI  - Cellular ultrastructure of the ruptured anterior cruciate ligament. A
      transmission electron microscopic and immunohistochemical study in 55 cases.
AB  - To evaluate the cellular ultrastructure following injury, we examined the
      anterior cruciate ligaments in 55 patients with complete tears in different
      phases after the injury and compared them to a control group of 39 cadaver knees.
      Samples were analyzed by electron microscopy, immunofluorescence, and
      ultramorphometry. After an invasion of inflammatory cells into the stumps of the
      ruptured ligaments, a marked proliferation of fibroblasts was found at the end of
      Phase 1 (2-3 days after the ligament injury), that was even more pronounced at
      the beginning of Phase II (4-17 days). These cells were initially highly
      metabolically active and secreted Type III collagen precursors. In Phase III (4
      45 days), fibroblast degeneration occurred with increasing frequency.
      Furthermore, some fibroblasts showed signs of cell death. Our findings suggest
      that the structural alterations of the intraligamentous fibroblasts diminish
      their function and, consecutively, disorganization of the developing repair
      tissue occurs. This mechanism might contribute to the poor healing potential of
      the ruptured anterior cruciate ligament.

PMID- 8154290
TI  - Osteochondritis dissecans of the patella. 12 cases followed for 4 years.
AB  - Osteochondritis dissecans of the patella in 9 patients (6 men, 3 women; mean age
      19 years) was located in the median ridge and paramedial areas and was bilateral
      in 3 patients. All patients were initially treated conservatively with complete
      relief of symptoms in 5. In 7 patients fragments were excised and the crater was
      curetted and drilled. At follow-up after 4 (2-8) years, the patients had no
      restriction of activities and they had no pain.

PMID- 8154291
TI  - External fixation test in low back pain. Function analyzed in 25 patients.
AB  - We recorded the musculoskeletal performance capacity of 25 patients suffering
      from chronic severe low back pain before and during the external fixation test of
      the lumbar spine. The capacity was measured by isometric and isokinetic lifting,
      repetitive upper extremity lifting with a load, repetitive squatting, and the
      walking distance. Only walking distance was increased by fixation of the spine.

PMID- 8154292
TI  - Life expectancy after hip arthroplasty. Case-control study of 1018 cases of
      primary arthrosis.
AB  - The long-term survival of 1018 total hip arthroplasty (THA) patients (237 McKee
      Farrar, 449 Brunswik and 332 Lubinus patients) operated on for primary arthrosis
      was compared with pair-matched controls (i.e., patients operated on for other
      orthopedic indications) and with a normal population. The 10-year survival after
      surgery for the McKee-Farrar patients was 85 percent, for the Brunswik patients
      82 percent, for the Lubinus patients 82 percent and for the orthopedic control
      patients 84 percent, respectively. The 10-year survival after 65 years of age for
      the THA patients was 78 percent and for the normal population 73 percent. The
      long-term life expectancy of our patients with a cemented THA was equal to that
      of our orthopedic control group and better than the life expectancy of the
      Finnish population.

PMID- 8154293
TI  - Direct repair of lumbar spondylolysis. 10-year follow-up of 12 previously
      reported cases.
AB  - Direct repair of the pars interarticularis defect in lumbar spondylolysis had
      been performed on 12 patients (mean age 29 years). After an average follow-up
      period of 10 years, 10 patients had a good result, 1 fair but improved and 1 poor
      with unchanged complaints.

PMID- 8154294
TI  - Infection after reamed intramedullary nailing of lower limb fractures. A review
      of 1,464 cases over 15 years.
AB  - We studied 1,464 consecutive immediately-reamed intramedullary locked nailings of
      tibial or femoral fractures. There was an increase in postoperative infection if
      the tibial fracture was open; the relative risk increased with the severity of
      the soft tissue lesion. There was a marginal increase in the postoperative
      infection rate for open femoral fractures. A comparison of these figures with
      those in other methods of treatment and the mechanical and clinical advantages of
      nailing leads us to propose this method of treatment for Grades I and II open
      fractures of the femur or tibia.

PMID- 8154295
TI  - Carpal bossing with capitate-trapezoid fusion. A case report.

PMID- 8154296
TI  - Lengthening a short femoral amputation stump. A case of tissue expander and
      endoprosthesis.

PMID- 8154297
TI  - Rigidity, sensitivity and quality of attachment: the role of maternal rigidity in
      the early socio-emotional development of premature infants.
AB  - The associations between a mother's rigidity, her sensitivity in early (3 month)
      interaction and the quality of her premature infant's attachment at 13 months
      were investigated. Rigidity as a personality characteristic was not found to be
      significantly associated with sensitivity or quality of attachment. Rigid
      attitudes to child rearing were related to sensitivity and to the responsivity of
      the infant. Rigid attitudes were not related to security of attachment. Infants
      who were rated less responsive at 3 months, however, tended to be less securely
      attached, and high Attitude Rigidity in the mother increased their chances of an
      insecure attachment.

PMID- 8154298
TI  - Assay of antioxidants by the quenching of the anthracene-sensitized
      electrochemiluminescence.
AB  - The kinetic and spectral characteristics (chemiluminescence and fluorescence
      spectra) of ultraweak luminescence accompanying the electrolysis of a sodium
      citrate-methanol-dissolved O2 solution and its application for the determination
      of antioxidants were examined. The energy transfer-assisted luminescence
      sensitized by anthracene provides a fast and sensitive assay for the
      determination of the concentration and kinetic parameters of antioxidants and
      free radical scavengers.

PMID- 8154299
TI  - Improvements to enhanced horseradish peroxidase detection sensitivity.
AB  - At very low horseradish peroxidase (HRP) concentrations, the enhanced
      chemiluminescence reaction is often characterized by a lag time between
      initiation of the reaction and beginning of light output. In this study, four
      treatments of luminol solution were examined in an effort to remove the lag time
      and to improve chemiluminescence light output. Addition of ammonium persulphate
      stimulated light output more than tenfold. Ultraviolet irradiation and
      photoactive dye pretreatment of luminol solution both increased light output
      fourfold. Luminol purity was the most important factor affecting detection
      sensitivity. Recrystallization of luminol from base improved the detection limit
      13-fold although there was an improvement in the detection limit from 13
      attomoles per millilitre to 5 attomoles per millilitre with highly purified
      luminol when photoactive dye pretreatment was utilized. The results are
      consistent with a simple interference mechanism whereby enhancer radicals
      produced by the enzyme are preferentially quenched by contaminants present in the
      luminol, in the enhancer and in the solvent used to dissolve the enhancer.
      Consumption of these interferences prior to light emission results in a lag time
      and a less favourable HRP detection limit.

PMID- 8154300
TI  - Acridinium ester labelled cytokines: receptor binding studies with human
      interleukin-1 alpha, interleukin-1 beta and interferon-gamma.
AB  - As a consequence of environmental protection and legal restrictions, increasing
      efforts are made to avoid radioactivity. One alternative is the labelling of
      ligands with chemiluminescent acridinium esters such as 2,6-dimethyl-4-(N
      succinimidyloxy-carbonyl)phenyl 10-methylacridinium-9-carboxylate methosulphate
      (DMAE-NHS). When exposed to hydrogen peroxide in a basic solution, the DMAE
      moiety decays with emission of a short-lasting chemiluminescent flash. With the
      goal of replacing the radioactive label in protein ligands with a DMAE label, and
      of increasing the efficiency by using microtitre plate technology for DMAE
      detection, we compared the receptor binding properties of iodinated interleukin-1
      alpha (125I-IL-1 alpha), interleukin-1 beta (125I-IL-1 beta) and interferon-gamma
      (125I-IFN-gamma) with the corresponding DMAE-labelled ligands. The luminescence
      signal was assessed in a single-tube luminometer and in the prototype of a
      chemiluminescent microtitre plate reader. Derivatization of the three proteins
      with DMAE-N-hydroxy-succinimide resulted in photon yields of up to 100,000 counts
      per femtomole. As shown by Scatchard analysis, no significant loss of receptor
      binding affinity was observed, which might have been expected as a consequence of
      the chemical modification of the proteins. The use of DMAE labelling of proteins
      has the following advantages as compared to iodination: (i) the coupling reaction
      and binding assay can be performed in a normal laboratory, (ii) since there is no
      radiolysis, the DMAE-labelled proteins remain stable, (iii) the detection
      sensitivity may be improved as a consequence of higher specific activity of the
      DMAE label.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154301
TI  - Apyrase immobilized on paramagnetic beads used to improve detection limits in
      bioluminometric ATP monitoring.
AB  - A novel technique that is useful for the control of the luminescence output in a
      bioluminometric assay has been developed. The method relies on the immobilization
      on paramagnetic beads of an enzyme that is capable of catalysing the hydrolysis
      or oxidation of the substrate for the luminescence reaction. This technique has
      been used for control of the level of ATP in the luciferin-luciferase system.
      Biotinylated apyrase was bound to streptavidin coated paramagnetic beads and
      added to the assay mixture. The level of ATP in the reaction mixture was then
      conveniently controlled using an external magnet. The possible use of this
      approach in other systems, such as the bacterial luciferase-oxidoreductase is
      discussed.

PMID- 8154302
TI  - Enhancers of the non-peroxidative metal porphyrin chemiluminescence reaction.
AB  - Metal porphyrins catalyse luminol chemiluminescence at pH13 without added
      peroxide. The effects of 22 different surface active compounds on this reaction
      were studied using six metal porphyrins and one metal porphyrin conjugate. The
      most active catalyst was Mn-meso-tetra(4-sulphonatophenyl)porphine. Tween-20
      enhanced the activity of this catalyst best at a Tween-20 to luminol ratio of
      74:1. However, lauryl sulphate enhanced best at an optimum lauryl sulphate to
      luminol ratio of over 1000:1 and both detergents enhanced the reaction when
      present below their critical micelle concentrations. Negatively charged aliphatic
      compounds such as fatty acids enhanced the reaction but positive-charged
      aliphatic compounds inhibited it. Small differences in enhancer structure
      resulted in differing enhancement. For example, linoleic acid enhanced Mn-meso
      tetraphenyl porphine more than 10-fold, yet linolenic acid inhibited this
      catalyst. Conjugation of a metal porphyrin to antibody did not influence its
      enhancement by detergents. The results indicate that the enhancement mechanism
      does not require formation of pure detergent micelles but that direct association
      between enhancer and catalyst may be important.

PMID- 8154303
TI  - Changes in bone mass early after kidney transplantation.
AB  - Renal transplant patients exhibit increased rates of trabecular bone fractures,
      probably due to glucocorticoid-induced osteopenia, which is known to occur within
      6 months after kidney grafting. This mineral loss at a mostly trabecular site
      (lumbar spine) contrasts with a gain at the radius, which consists mainly of
      cortical bone. However, the early effects of kidney transplantation on the other
      parts of the human skeleton and the time course of these changes during the first
      5 months after transplantation remain unknown. Therefore, 34 kidney transplant
      recipients were prospectively followed immediately after kidney grafting (12 +/-
      1 days, mean +/- SEM, and then on a monthly basis up to 152 +/- 3 days) and
      compared with 34 normal healthy volunteers matched for age, sex, and body mass
      index. Bone mineral measurements of whole body (n = 34), lumbar spine (n = 32),
      and upper femur (n = 23) were performed using dual-energy x-ray absorptiometry
      (Hologic QDR 1000W). At time of transplantation, lumbar bone mineral density
      (BMD) and BMD of the upper femur were lower (p < 0.01) in female but not male
      patients compared with controls. Lumbar BMD decreased by 1.6 +/- 0.2% per month
      in both sexes (p < 0.01), whereas BMD of upper femur further decreased in males
      (p < 0.01) but only tended to decrease in females. At time of transplantation,
      whole-body bone area (BA), bone mineral content (BMC), and BMD were decreased by
      about 8, 15, and 9%, respectively, in patients compared with controls (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154304
TI  - Absence of paramyxovirus RNA in cultures of pagetic bone cells and in pagetic
      bone.
AB  - It has been proposed that Paget's disease of bone is caused by the infection of
      bone cells with one or several paramyxoviruses. In this study we used the
      polymerase chain reaction (PCR), which allows the detection of very low levels of
      a target nucleic acid sequence, to study cultures of pagetic bone cells and
      samples of pagetic bone. Oligonucleotide primers were designed to flank a
      sequence of the nucleocapsid genome of measles virus and canine distemper virus
      (CDV). Within this fragment there were contrasting restriction endonuclease sites
      specific to measles or CDV that allowed identification of the original template.
      We were unable to detect paramyxovirus RNA in four strains of human bone cells
      outgrown from pagetic bone and one strain derived from an uninvolved site of a
      patient with Paget's disease. Furthermore, paramyxovirus sequences were not
      detected in cDNA prepared from six samples of pagetic bone biopsies. The work
      presented here further questions the role of measles and CDV in the abnormal
      remodeling observed in Paget's disease.

PMID- 8154305
TI  - Accuracy, precision, and utility of spine and whole-skeleton mineral measurements
      by DXA in rats.
AB  - We evaluated the precision and accuracy of dual-energy x-ray bone densitometry
      (DXA) in 38 male and female rats aged 1-10 months. The coefficients of variation
      (CV) estimated from same-day paired measurements of bone mineral content (BMC)
      were 1.26% at the lumbar spine and 0.69% at the whole skeleton, and the
      corresponding CV for BMC corrected for projected bone area (i.e., bone mineral
      density, BMD) were 0.57 and 0.66%. BMC, measured in vivo, correlated closely with
      the subsequently determined ash weights (spine r2 = 0.94, whole-skeleton r2 =
      0.97). The long-term CV for BMC measurements, assessed by measuring a frozen
      animal daily for 4 weeks, were 1.28% for the spine and 1.03% for the whole
      skeleton; for BMD the corresponding CV were 0.88 and 1.15%. To examine the
      utility of serial DXA measurements we followed female rats subjected to
      ovariectomy (OVX) or sham operation at 10 months of age and male rats given daily
      subcutaneous injections of hPTH-(1-34) or vehicle starting at 10 months of age
      every 3 weeks for 15 weeks. In the OVX rats a progressive decrease in spine BMC
      was observed that was most rapid during the first 6 weeks. By 15 weeks the mean
      spine BMC decreased by 17% in the OVX rats (p < 0.007 versus sham operation). OVX
      did not affect the accuracy of DXA measurements as assessed by comparison with
      the ash weight at the end of the 15 week study. PTH treatment increased spine BMC
      by a mean of 32% and increased whole-skeleton BMC by a mean of 19% within 15
      weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154306
TI  - Automated three-dimensional characterization of osteoclastic resorption lacunae
      by stereoscopic scanning electron microscopy.
AB  - The use of stereoscopic scanning electron microscopy to analyze quantitatively
      the topography of excavations made by osteoclasts in slices of devitalized
      cortical bone was evaluated. Using this innovative technique, the need
      mechanically to tilt the specimen stage to gather three-dimensional information
      is obviated by instead tilting the electron beam both to produce real-time stereo
      pairs and to gather measurement data. Based on the comparison of two images of
      microscopic areas, cross-correlation is used to determine the image shift between
      the features in the stereo pair. This information is then used dynamically to
      correct the height of the tilt axis and lens focus in a feedback loop, generating
      a quantitative measurement of height difference. With this approach, relative
      heights of individual points, line profiles, area topography maps, and three
      dimensional reconstructions of excavations were obtained rapidly and at high
      resolution. This approach combines the advantage in topographic data acquisition
      of confocal microscopy with the advantages of the increased resolution and focal
      depth of scanning electron microscopy (SEM). The technique should facilitate not
      only the topographic analysis of osteoclastic excavations in bone slices at high
      resolution but also the three-dimensional analysis of the structure of bone
      tissue.

PMID- 8154307
TI  - Histochemical and autoradiographic studies on elcatonin internalization and
      intracellular movement in osteoclasts.
AB  - The binding sites and chronologic localization of elcatonin (eCT) in osteoclasts
      were examined by autoradiography using [125I]elcatonin (125I-eCT). In addition to
      the structural changes induced by calcitonin (CT) reported so far, changes were
      also observed in the structure of Golgi apparatus. These changes continued until
      48-72 h after incubation with eCT. Developed silver grains of 125I-eCT were
      localized into multinucleated osteoclasts and mononuclear cells that were
      ultrastructurally defined as "preosteoclasts." The silver grains located on
      plasma membranes of those cells and were then internalized; they accumulated,
      especially in the Golgi apparatus, and remained for 48-72 h. A few silver grains
      were also detected in lysosomes and small vesicles. The decrease in the number of
      silver grains in the Golgi apparatus accompanied the recovery of osteoclast
      structures--Golgi apparatus and then ruffled borders. These findings suggest that
      (1) CT especially inhibits the sorting function of Golgi apparatus in
      osteoclasts, resulting in prolonged retention of CT in this organelle. (2) The CT
      in Golgi apparatus may keep its activity and cause the prolonged effect of CT on
      osteoclast activity.

PMID- 8154308
TI  - Grip strength and bone mineral density in older women.
AB  - Most previous literature on muscle strength and bone density examined the
      association between specific muscle groups and adjacent bones. This study
      examined the association of grip strength with bone density at distant sites,
      such as the spine and hip, as well as at the wrist and radius. Subjects were 649
      postmenopausal women aged 65 years and older. Bone mineral density was measured
      at the ultradistal wrist and midshaft radius in the nondominant arm using single
      photon absorptiometry and at the lumbar spine and hip using dual-energy x-ray
      absorptiometry. Grip strength was measured in both the dominant and nondominant
      hands using a dynamometer. Overweight women had significantly stronger grip
      strength in both hands (p < 0.01 for dominant hand, p < 0.05 for nondominant hand
      grip strengths). Exercises had significantly stronger grip strength in the
      nondominant hand than nonexercisers (p < 0.05). Women reporting arthritis had
      significantly weaker grip strength in both hands than women not reporting
      arthritis (p < 0.001). There were no significant differences in grip strength by
      estrogen use, cigarette smoking, or thiazide use. Regression analyses adjusted
      for age, obesity, exercise, cigarette smoking, thiazide use, arthritis, years
      postmenopausal, and estrogen use indicated significant positive associations
      between grip strength and bone density at all sites. Regression analyses
      stratified by exercise indicated that only women who exercised had significant
      associations of grip strength with bone mineral density (all p < 0.05). In this
      cohort of older women, grip strength was an independent indicator of general bone
      density.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154309
TI  - Calcitriol corrects deficient calcitonin secretion in the vitamin D-deficient
      elderly.
AB  - The thyroid calcitonin-producing C cells possess vitamin D receptors and
      synthesize the vitamin D-dependent calbindin D28K. The present study evaluates
      the possible direct or indirect influence of vitamin D on calcitonin secretion in
      the elderly. Serum calcitonin was measured before and after a short calcium
      infusion (1.5 mg/kg over 10 minutes) in nine normal young adults (30 +/- 4 years,
      mean +/- SEM) and eight elderly subjects (78 +/- 4 years). The test was repeated
      48 h after the last of three intravenous injections of calcitriol (2 micrograms)
      given every other day. Basal serum calcium did not change, but basal calcitonin
      of the elderly increased from 7 +/- 1 to 10 +/- 1 pg/ml (p < 0.06), similar to
      basal values in young adults (11 +/- 1 pg/ml). The increase in calcitonin after
      calcium infusion increased from 8 +/- 1 to 14 +/- 1 pg/ml (p < 0.001) after
      calcitriol treatment and approached the increase in young adults (18 +/- 3
      pg/ml). These data demonstrate that calcitriol can improve and nearly normalize
      the impaired calcitonin secretion of the mildly vitamin D-deficient elderly
      subjects without changes in serum calcium, whereas the inverse situation is
      observed for parathyroid hormone.

PMID- 8154310
TI  - Influence of age on cyclosporin A-induced alterations in bone mineral metabolism
      in the rat in vivo.
AB  - Cyclosporin A (CsA) administered to actively growing young rats produces a high
      turnover osteopenia. We investigated and compared the effect of CsA on the bone
      mineral metabolism in young rats with that of older rats, which have a lower rate
      of bone turnover. A group of 24 young (9 weeks) and 24 older (9 months) male
      Sprague-Dawley rats were orally administered 15 mg/kg of CsA or placebo daily for
      24 days. Rats were weighed and serum assayed serially for bone gla protein (BGP),
      parathyroid hormone, ionized calcium, blood urea nitrogen, creatinine, and 1,25
      dihydroxyvitamin D [1,25-(OH)2D]. After sacrifice, histomorphometric analysis was
      performed on undecalcified proximal tibial metaphysis with double-fluorescent
      labeling. Serum BGP levels were significantly elevated in both young and older
      rats administered CsA, and 1,25-(OH)2D levels were significantly elevated in CsA
      treated young rats more than in older rats. Body weight was significantly reduced
      in CsA-treated older rats. There were mild but significant alterations in renal
      function in both groups receiving CsA. In the most comprehensive examination to
      date of the effects of CsA on bone histomorphometry, both young (-44%) and older
      rats (-20%) lost significant amounts of trabecular bone compared to their
      respective controls. Bone loss in young rats was mainly due to a reduced number
      of trabecular; older rats lost mainly trabecular thickness. Microanatomic nodal
      studies were consistent with these results. These data demonstrate that although
      cancellous bone loss induced by CsA is more marked in young rats, older rats with
      slower bone turnover are also at risk.

PMID- 8154311
TI  - Long-term (3 years) prevention of trabecular postmenopausal bone loss with low
      dose intermittent nasal salmon calcitonin.
AB  - The long-term effect of intermittent low-dose nasal salmon calcitonin on
      trabecular early postmenopausal bone loss was assessed as follow-up to a
      previously published study. Randomized controlled group comparison was made of
      287 healthy women with 6-36 months of natural menopause and no treatment
      interfering with calcium metabolism at an outpatient clinic for research in bone
      and cartilage metabolism. The 287 women were randomly allocated to 3 years of
      treatment with either 500 mg/day, 5 days/week of calcium or the same amount of
      calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of
      186 women complied with the study protocol throughout. The main outcome measures
      were bone mineral density of the lumbar spine (DPA) and biochemical parameters
      reflecting bone turnover (serum alkaline phosphatases, urinary
      calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in
      bone mineral density after 36 months showed a positive (p < 0.05) outcome (1.8 +/
      5.7%; mean +/- SD) in the group treated with salmon calcitonin and calcium and a
      significant (p < 0.01) loss (-5.8 +/- 4.8%) in patients receiving calcium alone.
      The difference between the evolution of the two groups was significantly (p <
      0.01) different after 6 months of treatment and remained so until the end of the
      study. No significant changes were recorded in biochemical parameters reflecting
      bone turnover. As previously shown during a 1 year follow-up, nasal salmon
      calcitonin given at low dose and intermittently, in association with calcium, can
      counteract trabecular postmenopausal bone loss.

PMID- 8154312
TI  - Interleukin-6, IL-6 receptor, and IL-6 nuclear factor gene expression in Paget's
      disease.
AB  - The cytokine interleukin-6 (IL-6) is considered an important regulator of bone
      cell function and may play a central role in bone disease states characterized by
      increased bone remodeling, such as Paget's disease. Indeed, recent in vitro data
      suggest that IL-6 may be an autocrine/paracrine factor for pagetic osteoclasts.
      However, its expression and role in vivo are not known. Using in situ
      hybridization we investigated the spatial localization of expression of IL-6, IL
      6 receptor (IL-6R), and the transcription factor (NF-IL-6) in pagetic bone. Our
      results show that osteoblasts in the normal remodeling bone of osteoarthritis
      (controls) and in Paget's disease express IL-6, IL-6R, and NF-IL-6 genes with
      higher levels of IL-6 and IL-6R mRNA in pagetic bone. Osteoclasts in both
      osteoarthritic and pagetic bone express IL-6R mRNA and NF-IL-6, but only pagetic
      osteoclasts expressed IL-6, suggesting that in Paget's disease IL-6 can act as an
      autocrine factor on osteoclasts. These results provide evidence for a major role
      of the IL-6 regulatory pathway in the phenotype of the pagetic osteoclasts and
      lead us to suggest a model linking possible paramyxovirus infection and IL-6
      regulation in the pagetic osteoclast.

PMID- 8154313
TI  - Long-term elevation of 1,25-dihydroxyvitamin D after short-term intravenous
      administration of pamidronate (aminohydroxypropylidene bisphosphonate, APD) in
      Paget's disease of bone.
AB  - We report the prolonged biochemical changes that occurred in patients with
      Paget's disease when treated for 2-10 days with pamidronate disodium (3-amino-1
      hydroxypropylidine-1,1-bisphosphonate, APD), by i.v. administration and observed
      for 6 months following therapy. In all 24 patients studied, bone resorption
      (measured by urinary hydroxyproline/creatinine ratio, OHP/Cr) fell sharply on
      treatment, from 0.12 +/- 0.02 (mean +/- SEM; above reference limits) to 0.04 +/-
      0.008 (reference range 0.006-0.027 for females, 0.005-0.020 for males), remaining
      at this level for 6 months after therapy. A fall in serum ionized calcium (Ca2+)
      to just below the reference limits with treatment (1.11 +/- 0.02 mM; reference
      range 1.14-1.18 mM), followed by a rapid return to normal levels (1.14 +/- 0.02
      mM, mean +/- SEM) within 8 days of treatment, was presumably due to the cessation
      of release of calcium from bone. This was followed by secondary
      hyperparathyroidism and a rise in serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The
      hormonal responses, however, were profound. Serum immunoreactive PTH (iPTH) rose
      to twice pretreatment values (86 +/- 11 pM, mean +/- SEM; reference range for
      iPTH, > 50 years, < 50 pM; < 50 years, < 40 pM), returning to normal 4-8 weeks
      after therapy. Serum 1,25-(OH)2D levels rose to three times pretreatment values
      (300 +/- 20 pM, mean +/- SEM; reference range 50-150 pM), remaining above
      reference limits 4-8 weeks after therapy (188 +/- 15 pM, mean +/- SEM) and
      returning to normal values only after 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154314
TI  - Mechanical loading thresholds for lamellar and woven bone formation.
AB  - Bone formation was measured in rat tibiae after 12 days of applied loading.
      Bending forces were applied using a four-point loading apparatus. Sham loads were
      applied at the same magnitudes as bending forces but the loading pads were
      arranged so that bending was minimized. Bending and sham loading were applied to
      the right tibiae of rats and the left tibiae served as contralateral controls.
      Loading was applied as a sine wave with a frequency of 2 Hz for 18 s (36 cycles)
      per day. The peak magnitude of applied load was 27, 33, 40, 52, and 64 N. Woven
      bone was observed on the periosteal surface in all animals subjected to loads of
      40 N or greater. Periosteal woven bone formation occurred in both bending and
      sham loading groups. Woven bone formation on the periosteal surface was either
      absent or responded at a maximal rate if the stimulus threshold was surpassed.
      The amount of new woven bone and the woven bone-forming surface were independent
      of the magnitude of applied strain. Bone formation on the endocortical surface
      was exclusively lamellar. Lamellar bone formation was stimulated by applied
      bending of the tibia but not by sham loading. Bending strains above a loading
      threshold of 40 N or about 1050 mu strain increased both bone-forming surface and
      the mineral apposition rate and subsequently increased the bone formation rate as
      much as sixfold. No evidence of increased bone formation was seen for applied
      strains below 1050 mu strain. Examination of bulk stained sections from animals
      exposed to the highest applied loads showed no evidence of microcracks.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8154315
TI  - Transforming growth factor beta increases ecto-nucleoside triphosphate
      pyrophosphatase activity of human bone-derived cells.
AB  - Inorganic pyrophosphate (PPi) may be involved in the regulation of
      mineralization. The cell surface enzyme, ecto-NTP pyrophosphatase, could be a
      major source of extracellular PPi in bone, and agents that influence its activity
      in osteoblasts may modulate bone mineralization. We studied the effects of serum
      on the ecto-NTP pyrophosphatase activity of cultured human osteoblast-like cells.
      Enzyme activity was lowered when the concentration of fetal calf serum (FCS) was
      reduced from 10 to 2.5% (vol/vol) for 48 h, and a further decrease in activity
      was observed after 96 h. Relative to enzyme activity in cells cultured in serum
      free medium for 96 h, adult human platelet-poor plasma (HPPP; 2.5-10% vol/vol)
      induced a small increase, similar concentrations of adult human serum (HS)
      induced much larger increases, and charcoal-depleted FCS was ineffective. In an
      attempt to identify the factor(s) present in serum that influence ecto-NTP
      pyrophosphatase activity, we examined transforming growth factor-beta (TGF-beta)
      and platelet-derived growth factor (PDGF). PDGFs AA, AB, and BB (0.1-10 ng/ml)
      were ineffective, but both TGF-beta 1 and TGF-beta 2 increased enzyme activity.
      The increase was dose dependent between 0.001 and 10 ng/ml, was enhanced in the
      presence of 2% vol/vol FCS, and was not potentiated by PDGF or by 1,25-(OH)2D3.
      Furthermore, the increase was independent of cell density and was blocked by
      inhibitors of protein and RNA synthesis. Ecto-NTP pyrophosphatase of subject
      matched human dermal fibroblasts was unaffected by TGF-beta (10 ng/ml),
      suggesting that modulation of activity by the growth factor may be tissue
      specific. Alkaline phosphatase (ALP) probably serves to hydrolyze extracellular
      PPi in bone. In contrast to effects on NTP pyrophosphatase activity is osteoblast
      like cells, TGF-beta 1 and TGF-beta 2 (0.001-10 ng/ml) decreased ALP activity
      dose dependently after 72 h. By inducing opposing changes in ecto-NTP
      pyrophosphatase and ALP activities, TGF-beta may increase extracellular PPi
      concentrations in osseous tissues and consequently modulate bone mineral
      properties in vivo.

PMID- 8154316
TI  - Interaction between human medulloblastomas and foetal rat brain aggregates in
      vitro.
AB  - The invasiveness of three medulloblastoma permanent cell lines (D-283, D-341, and
      DAOY), a human medulloblastoma biopsy, and in addition, a human rhabdomyosarcoma
      permanent cell line (TE-671), which previously had been regarded as a human
      medulloblastoma, was studied in an organ co-culture assay. All the four cell
      lines and the biopsy were co-cultured with normal rat brain cell aggregates for
      up to six days in vitro. The medulloblastoma biopsy, the D-283 and the D-341
      cells invaded the brain tissue by diffuse single cell infiltration. The
      medulloblastoma cell line (DAOY) showed an invasive pattern similar to that
      observed earlier for most glioblastoma cell lines. This was characterized by
      massive cell replacement and destruction of normal brain tissue. The
      rhabdomyosarcoma cell line (TE-671) presented a solid invasive pattern with a
      fairly well defined border between normal brain and tumour tissue. Thus, the
      organ co-culture assay system in vitro seems to mimic several aspects of the in
      situ invasive behaviour of medulloblastomas. It may, therefore, provide new
      perspectives for pretreatment investigations with chemotherapy and radiotherapy
      of these malignancies.

PMID- 8154317
TI  - Karyotype analyses of 20 human glioma cell lines.
AB  - Human malignant gliomas are frequently associated with loss of gonosomes and
      chromosomes 13, 17, and 22. Their progression from anaplastic glioma to
      glioblastoma is marked by additional loss of chromosome 10. In addition,
      structural and numerical aberrations of chromosome 7 are frequently found. We
      report on the karyotypes of a series of 20 human gliomas of which 11 were
      analysed as established cell lines; 9 cases were investigated in early culture, 5
      of which later also became established lines. In addition to the frequently
      reported overrepresentation of chromosome 7, four cell lines with polysomy for
      chromosome 22 were seen. A high incidence of structural chromosomal aberrations
      was present in early cultures as well as in cell lines after various in vitro
      passages. We found that the general characteristics of karyotypic aberrations
      found in early cultures or direct preparations of dispersed tumour material were
      reflected in the pattern of aberrations present in cell lines at much later time
      points. Thus it appears as if no systematic changes can be attributed to long
      term cultures. Suspicious losses of chromosomes 14, 18, and 19 or gain of
      chromosome 22 indicate that individual cases may have originated due to other
      mechanisms than the ones already hypothesized, i.e., different suppressor genes
      or amplification of genes other than the EGF-R-gene. None of the established cell
      lines had a genomic rearrangement of c-erbB 1, c-erbB 2 or of the p 53 gene.

PMID- 8154318
TI  - Surgical treatment of meningiomas of the orbit and optic canal: a retrospective
      study with particular attention to the visual outcome.
AB  - A series of 57 patients affected either by optic nerve sheath meningiomas (15
      patients) or by secondary meningiomas extending into the orbital apex or optic
      canal (42 patients) has been reviewed. Proptosis (80%), progressive visual loss
      (76%), and visual fields defects (63%) were the most common pre-operative
      complaints. All patients underwent transcranial surgery. Radical tumour resection
      was possible in 9 out of 15 primary and 22 out of 32 secondary tumours. Overall,
      27% of the patients obtained improved postoperative visual acuity, 62% remained
      unchanged, and 11% were worse. The postoperative visual outcome was related to
      the degree of pre-operative visual impairment. In a period between 38 and 68
      months, 5 meningiomas recurred. The time to progression of partially resected
      lesions ranged between 9 and 68 months.

PMID- 8154319
TI  - Early management in poor grade aneurysm patients.
AB  - Aneurysm surgery began in Lubeck only in 1986 when the department was completely
      reorganized. Early operation in the good grade patients (I-III, according to Hunt
      and Hess) was performed. In every case we also discussed the feasibility of
      operating on the poor grade patients (Hunt and Hess IV and V). During a five-year
      period (1986-1991) a total of 277 SAH patients were admitted to the department.
      109 (39%) patients arrived in a poor grade (Hunt and Hess IV or V), 12 of these
      patients died within hours of admission. 25 patients, who presented with a large
      intracerebral and/or subdural haematoma, were urgently operated upon by haematoma
      evacuation and aneurysm clipping. An external ventricular drainage was performed
      on 72 patients. Of the ventriculostomy group 33 patients improved and 27 were
      operated upon. In 17 of the 39 patients without improvement after CSF-drainage we
      decided to operate. Overall 69 patients were surgically treated (craniotomy,
      aneurysm clipping) and 40 were not. The mortality rate in the surgical cases was
      16 (23%) compared with 30 (75%) without operation. It is concluded that poor
      grade aneurysm patients can achieve a better outcome with active treatment based
      on immediate ventriculostomy and optimal haemodynamic parameters after haematoma
      evacuation and early occlusion of the aneurysm.

PMID- 8154321
TI  - Gain and loss of the ability to compete. Some aspects of German neurosurgery up
      to 1939.
AB  - Sketchy biographies of 4 German neurosurgeons (Krause, Foerster, Stieda, Tonnis)
      demonstrate how neurosurgery in Germany rapidly developed and flourished from the
      end of the 19th century to the middle of the thirties. However, the dictatorship
      of Hitler, racial persecution, and the Second World War disturbed this promising
      development markedly and the aftermath was prolonged. It took many years to
      restore disrupted international relations and to regain the ability to compete in
      the scientific field.

PMID- 8154320
TI  - The anterior pituitary lobe in patients with cystic craniopharyngiomas: three
      cases of associated lymphocytic hypophysitis.
AB  - Specimens of the anterior pituitary lobe were investigated histologically in 28
      craniopharyngioma patients operated on trans-sphenoidally. The pituitary glands
      in 3 patients revealed lymphocytic invasion giving a histological appearance
      typical of lymphocytic hypophysitis (incidence: 11%). At follow-up examination
      all three patients with associated lymphocytic hypophysitis had complete
      pituitary insufficiency, whereas only 36% of the craniopharyngioma patients
      without associated lymphocytic hypophysitis were in this poor postoperative
      endocrine state. The phenomenon of associated lymphocytic hypophysitis in
      craniopharyngioma patients has not been reported so far. This might be due to the
      fact that investigators have failed to systematically examine the anterior
      pituitary lobe in craniopharyngioma patients. The 60 cases of lymphocytic
      hypophysitis reported in the literature occurred, for the most part, in women
      during late pregnancy or shortly after delivery. An auto-immune origin is assumed
      in this type of inflammation. In contrast to this pathophysiological mechanism,
      we assume a local induction of inflammation resulting from the craniopharyngioma
      cyst in our 3 patients.

PMID- 8154322
TI  - Analysis of 20 primarily surgically treated chiasmatic/hypothalamic pilocytic
      astrocytomas.
AB  - The authors review the therapeutic results of 20 patients (aged 12 months to 30
      years, mean age 9 years) with benign pilocytic astrocytoma of the
      chiasmatic/hypothalamic region, seen at the University Hospital Hamburg-Eppendorf
      between February 1980 and April 1993. Six patients suffered from
      neurofibromatosis 1 (NF-1). The patients were divided into two subgroups relative
      to tumour extension and growth patterns, as revealed by CT scans and/or MR
      imaging. Fourteen patients revealed a large globular suprasellar tumour extending
      into the hypothalamus and/or the anterior third ventricle (group A). A
      suprasellar tumour with optic tract involvement could be identified in six cases
      (group B). Subtotal (70-90%) resection was achieved in ten tumours (50%), the
      majority of which were of the large globular type. There were no deaths.
      Postoperative morbidity was comprised of visual and endocrine impairment in four
      patients and right hemiparesis and dysphasia in one patient. Radiation therapy
      was given in nine cases (45%). Three tumours (38%) were reduced in size by
      irradiation. Tumour progression was seen in seven patients (35%). The presence of
      young age and NF-1 were predictors of progressive disease in our series. Growth
      capacity was not related to the extent of cytoreductive surgery.

PMID- 8154323
TI  - Protein tyrosine phosphatases: mechanism of catalysis and substrate specificity.

PMID- 8154324
TI  - Structure and mechanism of bovine lens leucine aminopeptidase.

PMID- 8154325
TI  - Heterologous expression of mammalian P450 enzymes.

PMID- 8154326
TI  - Aspartate transcarbamylase from Escherichia coli: activity and regulation.

PMID- 8154327
TI  - The rational design of thrombin-directed antithrombotics.

PMID- 8154328
TI  - Peptide boronic acid inhibitors of thrombin.

PMID- 8154329
TI  - In vitro and in vivo properties of synthetic inhibitors of thrombin: recent
      advances.

PMID- 8154330
TI  - The use of isosteric bonds in the design of thrombin inhibitors.

PMID- 8154331
TI  - Synthetic thrombin inhibitors as anticoagulants pharmacological aspects.

PMID- 8154332
TI  - X-ray crystal structures of thrombin in complex with D-Phe-Pro-Arg and with small
      benzamidine- and arginine-based "non-peptidic" inhibitors.

PMID- 8154333
TI  - New peptide boronic acid inhibitors of thrombin.

PMID- 8154334
TI  - Substrate-related phosphonopeptides as thrombin inhibitors.

PMID- 8154335
TI  - The synthesis and anticoagulant activity of novel peptidylfluoroalkanes.

PMID- 8154336
TI  - Transition state analogue inhibitors of thrombin: synthesis, activity and
      molecular modelling.

PMID- 8154337
TI  - Hirudin: the famous anticoagulant agent.

PMID- 8154338
TI  - Mechanisms for the anticoagulant effects of synthetic antithrombins.
AB  - The important roles of thrombin in the development and propagation of thrombosis
      are well recognized. In addition to being the enzyme for clotting fibrinogen (the
      major protein component of blood clots), thrombin accelerates its own generation
      by activating factor V, factor VIII, factor XI and platelets. It accelerates the
      stabilization of clots by activating factor XIII to factor XIIIa, the enzyme
      which crosslinks fibrin. There are probably two major pathways for regulating the
      availability of thrombin in vivo: inactivation of thrombin (by antithrombin
      III/vessel wall heparan sulfate and perhaps by other endogenous antithrombins)
      and the inactivation of factor Va and factor VIIIa by activated protein C. Factor
      Va and factor VIIIa accelerate the production of thrombin. However, when thrombin
      becomes bound to fibrin (in clots or possibly on cell surfaces), the ability of
      antithrombin III/heparin to inactivate thrombin is then reduced significantly.
      Impairment by fibrin of thrombin inhibition by antithrombin III may account in
      part for the inability of unfractionated heparin to prevent post-operative deep
      vein thrombosis in up to 20% of patients who undergo major elective orthopaedic
      surgery, and may also explain the need for oral anticoagulants after
      unfractionated and low molecular weight heparins are used to initiate the
      treatment of established deep vein thrombi. The ineffectiveness of the
      antithrombin III/heparin pathway for inhibiting thrombin under some circumstances
      has been a contributory factor for the development, evaluation and identification
      of other inhibitors of thrombin which are more able than antithrombin III/heparin
      to inactivate thrombin when the enzyme is bound to fibrin. The focus of this
      review is to detail how these synthetic agents, by directly or indirectly
      inactivating thrombin, can also effectively inhibit prothrombin activation in
      vitro.

PMID- 8154339
TI  - Pre-clinical and clinical studies on Hirulog: a potent and specific direct
      thrombin inhibitor.

PMID- 8154340
TI  - The effect of recombinant hirudin on arterial thrombosis.

PMID- 8154341
TI  - Inhibitor binding to thrombin: x-ray crystallographic studies.

PMID- 8154342
TI  - Molecular basis for the inhibition of thrombin by hirudin.

PMID- 8154343
TI  - Biophysical studies of interactions of hirudin analogs with bovine and human
      thrombin by ESR and fluorescence labelling studies.

PMID- 8154344
TI  - pH-dependent binding constants for the inhibition of thrombin by transition state
      analogs.

PMID- 8154345
TI  - The comparison of an interim tertiary predicted model of bovine thrombin and the
      x-ray structure of human thrombin.

PMID- 8154346
TI  - Design of novel types of thrombin inhibitors based on modified D-Phe-Pro-Arg
      sequences.

PMID- 8154347
TI  - Chemistry and biology of the peptide anticoagulant D-MePhe-Pro-Arg-H (GYKI
      14766).

PMID- 8154348
TI  - Renal lesions and pheochromocytoma in von Hippel-Lindau disease.

PMID- 8154349
TI  - Sickle cell nephropathy.

PMID- 8154350
TI  - Glomerulonephritis with organized microtubular monoclonal immunoglobulin
      deposits.

PMID- 8154351
TI  - Epithelial chloride channels, from kidney to airway cells.

PMID- 8154352
TI  - Primary periodic paralysis and muscle sodium channel.

PMID- 8154353
TI  - Experimental approaches to brush border morphogenesis.

PMID- 8154354
TI  - Adhesion molecules in nephrology.

PMID- 8154355
TI  - Role of nitric oxide in cardiovascular control in healthy subjects and in
      patients with renal failure.

PMID- 8154356
TI  - "Atriopeptidase" (EC 3.4.24.11) inhibition and protection of atrial natriuretic
      factor.

PMID- 8154357
TI  - Structure, function, and expression of the receptor for parathyroid hormone and
      parathyroid hormone-related peptide.

PMID- 8154358
TI  - Cellular mode of action of parathyroid hormone.
AB  - The current understanding of the cellular mode of action of PTH has undergone
      deep changes during the last decade and the major acquisitions can be summarized
      as follows. First, results from biochemical and cell biology studies suggest the
      existence of at least two receptor types coupled to two distinct intracellular
      signaling pathways by G proteins: the phospholipase C-calcium-protein kinase C
      pathway would be coupled to high-affinity receptors, whereas the adenylate
      cyclase-cAMP-protein kinase A pathway would be coupled to low-affinity receptors.
      Until now, only one type of PTH receptor has been identified at the molecular
      level. It is very likely that additional PTH receptor types will be evidenced.
      Second, both PTH receptor-coupled transduction pathways are involved in the
      inhibitory effect of the hormone on the activity of two transport systems of the
      apical membrane of proximal tubular cells: Na-Pi cotransport and Na-H exchanger.
      These effects are the cellular basis for PTH inhibition of Pi and bicarbonate
      reabsorption. Which proteins are the targets of the different protein kinases
      remains to be established. Concerning the other effects of PTH on the proximal
      tubule (stimulation of neoglucogenesis and of calcitriol synthesis, and Na, K
      ATPase inhibition), protein kinase C seems to play a major role. Third, in
      Henle's loop, PTH stimulates reabsorption of divalent cations through a dual
      effect under the dependence of protein kinase A, i.e., enhanced epithelial
      potential difference and opening of paracellular pathway. Finally, stimulation of
      distal calcium reabsorption results from multiple events: membrane insertion of
      apical calcium channels, opening of basolateral chloride channels resulting in
      cellular hyperpolarization, and modulation of Ca-ATPase. Again, while it is
      commonly acknowledged that both transduction systems are involved, their precise
      molecular targets remain to be identified (Table 1). The elucidation of the
      cellular mode of action of PTH, some examples of which have been reviewed, holds
      major interest far beyond the field of cell or organ physiology. It is the basis
      for understanding and, ultimately, for comprehensive treatment of genetic
      diseases characterized by functional abnormalities of molecules involved in the
      cascade of events leading to the effect of PTH on its cellular targets (hormone
      receptors, G proteins, and kinases). The second perspective is pharmacologic:
      molecular and structural identification of PTH-receptor interactions will be a
      prelude to design and synthesis of new selective, nonpeptidic hormonal analogs
      and antagonists that are easier to handle. The high incidence and severity of
      secondary hyperparathyroidism during chronic renal failure highlights the
      importance of this research.

PMID- 8154359
TI  - Parathyroid hormone-related protein: physiology and pathophysiology.

PMID- 8154360
TI  - von Hippel-Lindau disease: a model system for the isolation of "tumor suppressor"
      genes associated with the primary genetic mechanisms of cancer.

PMID- 8154361
TI  - Initiation of dialysis.

PMID- 8154362
TI  - Long-term cardiac morbidity and mortality during dialysis therapy.

PMID- 8154363
TI  - Strategy of cytomegalovirus infection prevention in renal transplantation.

PMID- 8154364
TI  - Interleukin-2 receptor-directed therapies: antibody- or cytokine-based targeting
      molecules.

PMID- 8154365
TI  - The kidney in the tuberous sclerosis complex.

PMID- 8154366
TI  - Renal cell carcinoma: recent progress.

PMID- 8154367
TI  - Pathophysiology of the podocyte: a target and a major player in
      glomerulonephritis.

PMID- 8154368
TI  - Structure and function of lipases.

PMID- 8154369
TI  - Structure of serum albumin.

PMID- 8154370
TI  - Apolipoprotein B and low-density lipoprotein structure: implications for
      biosynthesis of triglyceride-rich lipoproteins.
AB  - ApoB100 is a very large glycoprotein essential for triglyceride transport in
      vertebrates. It plays functional roles in lipoprotein biosynthesis in liver and
      intestine, and is the ligand recognized by the LDL receptor during receptor
      mediated endocytosis. ApoB100 is encoded by a single gene on chromosome 2, and
      the message undergoes a unique processing event to form apoB48 message in the
      human intestine, and, in some species, in liver as well. The primary sequence is
      relatively unique and appears unrelated to the sequences of other serum
      apolipoproteins, except for some possible homology with the receptor recognition
      sequence of apolipoprotein E. From its sequence, structure prediction shows the
      presence of both sheet and helix scattered along its length, but no transmembrane
      domains apart from the signal sequence. The multiple carbohydrate attachment
      sites have been identified, as well as the locations of most of its disulfides.
      ApoB is the single protein found on LDL. These lipoproteins are emulsion
      particles, containing a core of nonpolar cholesteryl ester and triglyceride oil,
      surrounded by an emulsifying agent, a monolayer of phospholipid, cholesterol, and
      a single molecule of apoB100. An emulsion particle model is developed to predict
      accurately the physical and compositional properties of an LDL of any given size.
      A variety of techniques have been employed to map apoB100 on the surface of the
      LDL, and all yield a model in which apoB surrounds the LDL like a belt. Moreover,
      it is concluded that apoB100 folds into a long, flexible structure with a cross
      section of about 20 x 54 A2 and a length of about 585 A. This structure is
      embedded in the surface coat of the LDL and makes contact with the core. During
      lipoprotein biosynthesis in tissue culture, truncated fragments of apoB100 are
      secreted on lipoproteins. Here, it was found that the lipoprotein core
      circumference was directly proportional to the apoB fragment size. A
      cotranslational model has been porposed for the lipoprotein assembly, which
      includes these structural features, and it is concluded that in permanent
      hepatocyte cell lines, apoB size determines lipoprotein core circumference.

PMID- 8154371
TI  - Apolipoprotein E: structure-function relationships.

PMID- 8154372
TI  - The amphipathic alpha helix: a multifunctional structural motif in plasma
      apolipoproteins.

PMID- 8154373
TI  - Lipophorin: the structure of an insect lipoprotein and its role in lipid
      transport in insects.

PMID- 8154374
TI  - Structure and catalytic mechanism of secretory phospholipases A2.

PMID- 8154375
TI  - Lipid-binding proteins: a family of fatty acid and retinoid transport proteins.

PMID- 8154376
TI  - [Necessity of electro-ophthalmological research].

PMID- 8154377
TI  - [Dielectric behavior of the rabbit cornea as a measure of the healing process in
      injured epithelium].
AB  - To correlate changes in the passive electrical properties of the rabbit cornea
      with quantitative grading of corneal injuries induced by topical application of
      70% ethanol, we measured ocular tissue impedances using a surface electrode over
      the range of 10(4)-10(8) Hz and followed their temporal changes for up to 17
      days. Dielectric measurements on control eyes yielded a broad dispersion curve,
      which, in loss tangent terms, could be decomposed into two components: dispersion
      1 on the low-frequency side and dispersion 2 on the high-frequency side. By
      defining the peak value of the total dispersion as Pt and those of subdispersions
      1 and 2 as P1 and P2, the ratios, P1/Pt and P2/Pt, were found to serve as useful
      indices. Upon appearance of corneal erosion due to ethanol, P1/Pt markedly
      increased and returned to the control level with re-epithelialization of the
      cornea, and the time course of P2/Pt showed a mirror image to that of P1/Pt. Both
      ratios correlated well with the erosion area determined photographically. These
      results indicate that dielectric spectroscopy is applicable to the assessment of
      the extent and severity of corneal injury.

PMID- 8154378
TI  - [An experimental study of diode laser photocoagulation and indocyanine green dye
      enhanced diode laser photocoagulation in the primate retina].
AB  - A diode laser, emitting light in the near-infrared range (803 nm), was used for
      photocoagulation at mild, moderate, and strong intensities with or without
      intravenous administration of indocyanine green (ICG) in 7 eyes of 4 rhesus
      monkeys. The retinochoroidal lesions were studied histopathologically from 24
      hours to 3 months after treatment, and choroidal vascular casts were studied by
      electron microscopy. Mild diode laser burns caused occlusion of the
      choriocapillaris and slight outer retinal damage. Moderate and severe burns
      caused more marked occlusion of the choriocapillaris, deep choroidal vessels, and
      choroidal nerves. There was little difference between ICG-enhanced and non
      enhanced mild burns, but ICG-enhanced moderate and severe burns showed larger
      retinochoroidal lesions and more complete obstruction of the choriocapillaris
      than did burns without ICG enhancement. It seems that at moderate and strong
      levels, ICG-enhanced diode laser burns have more apparent effect on the retina
      and choroid, particularly on the choroidal vessels.

PMID- 8154379
TI  - [The effect of ocular and/or pineal body removal in mice with spontaneously
      developing uveoretinitis].
AB  - Autoimmune uveoretinitis and pinealitis have been shown to develop spontaneously
      in BALB/c nude mice after their T cell function has been reconstituted by
      embryonic F344 rat thymus grafting (TG nude mice). Because anti-IRBP antibodies
      were detected in these mice, it was concluded that IRBP was the target antigen.
      In this study, we removed the eyes and/or the pineal body from TG nude mice, and
      examined anti-IRBP antibodies in their sera. It appeared that IRBP originating
      from the eyes and the pineal body were the immunogenic antigens in the TG nude
      mice, but the IRBP from the eyes was found to be more immunogenic and pathogenic
      than that from the pineal body. We also found that the incidence of uveoretinitis
      increases with pinealectomy in TG nude mice, even though the immune system is not
      affected.

PMID- 8154380
TI  - [Effect of calcium antagonist on retinal microcirculation evaluated with the
      laser speckle retinal microcirculation analyzer].
AB  - The effect of intravenous administration of a calcium antagonist on the retinal
      microcirculation in rabbit eyes was examined with a laser speckle retinal
      microcirculation analyzer. Under general anesthesia, 40 micrograms/kg of
      nicardipine, a calcium antagonist, was injected intravenously in the nicardipine
      group, and 0.4 ml/kg of saline in the control group. A quantitative index of
      blood flow velocity, the normalized blur (NB) value, in a retinal area (0. 62 x
      0.62 mm) free of visible vessels, was recorded at 1-minute intervals for the
      first 5 minutes and at 5 minute-intervals for the next 85 minutes. The retinal NB
      value in the nicardipine group was significantly greater than in the control
      group, averaging 119%, 115%, 111%, 112%, and 116% of the initial value at 65, 75,
      80, 85, and 90 minutes after injection, respectively. The blood pressure in the
      nicardipine group decreased significantly from 1 to 20 minutes after injection.
      The pulse rate, arterial pH, partial CO2 pressure, partial oxygen pressure, body
      temperature and intraocular pressure did not show significant change during the
      experiment. These results suggest, for the first time, that nicardipine increases
      the blood flow velocity in the retinal microvasculature in the living eye.

PMID- 8154381
TI  - [Firing patterns of the pontine omnipause neurons during sleep in the cat].
AB  - The omnipause neurons (OPNs), located in the nuculeus raphe pontis, cease firing
      during all rapid eye movements and otherwise fire at a steady rate in the awake
      state. Firing patterns of the OPNs were studied during the awake state, non-REM
      sleep, and REM sleep in chronically prepared adult cats, to examine whether the
      OPNs' firing participates in the genesis of eye movements during each state.
      During non-REM sleep, the OPNs continued their firing, and their firing patterns
      had little correlation with slow drifting eye movements appearing in this state.
      During REM sleep, the OPNs maintained a tonic firing and ceased their firing
      during rapid eye movements in all directions. These results suggest that
      cessation of OPN firing plays an important role in the generation of rapid eye
      movements during REM sleep as well as during the awake state in the cat.

PMID- 8154382
TI  - [Reducing cross-talk in electrooculograms made with several electrodes].
AB  - In order to discuss how to handle the contralateral effect (cross-talk) when
      taking an electrooculogram (EOG) with two or more electrodes, a forced duction
      test was used to detect cross-talk potentials. The cross-talk potentials
      originating from the left eye were measured at the right eye for 5 subjects when
      the left eye was adducted and abducted alternately with a suction contact lens
      while the right eye was kept fixed. The cross-talk potentials detected at the
      right eye did not depend on the electrode position, but the contralateral EOG
      potentials depended on the electrode position around the left eye. The cross-talk
      value is calculated as the gain, 20.log [(cross-talk potential)/(contralateral
      EOG potential)]. The denominator of this expression considerably affects the gain
      since the contralateral potential depends on the position of the electrode. We
      propose that the effect of the cross-talk on the potential between a pair of
      electrodes can be cancelled with the gain value (-15.0dB: the mean value for the
      5 subjects) when the contralateral electrode is set 20 mm from the outer canthus.

PMID- 8154383
TI  - [The difference between right and left eyes in the values obtained with a laser
      flare-cell meter].
AB  - The difference in various values, measured with a laser flare cell meter (FC1000:
      KOWA), between the right and left eyes was determined in 28 eyes of 14 healthy
      males, 18 to 23 years of age (group A), and in 60 eyes of 30 out-patients, 6 to
      68 years of age (group B). None of the eyes had any ocular pathology except for
      refractive error. Both groups of eyes were first evaluated without any treatment,
      and the eyes in group A were measured again after the instillation of mydriatics.
      The flare, signal, and background values were all statistically higher in the
      right eye than in the left in all subjects; the difference in the flare value
      between the two eyes was approximately 1 photon count/millisecond on the average.
      A regression analysis of the difference of the signal and the background values
      between the two eyes suggests that variation of the light scattered from behind
      the iris is responsible for the difference in the flare intensity between the
      right and the left eyes.

PMID- 8154384
TI  - [The difference between right and left in vitreous findings of normal eyes].
AB  - The vitreous in both normal eyes of 671 normal subjects was studied
      biomicroscopically. The results obtained were as follows: 1. In 618 cases of a
      refractive error less than -3D (group A) and 53 cases of refractive error over 
      3D (group B), the incidence of posterior vitreous detachment (PVD) in both eyes
      increased with age and the absence of PVD in both eyes decreased with age. The
      percentage of cases with PVD in one eye and no PVD in the other eye was less than
      22% in all age groups. 2. There was no significant difference in the degree of
      vitreous liquefaction between the right and the left eyes. The degree of vitreous
      liquefaction was also age-related. 3. In the cases with PVD in one eye and no PVD
      in the other eye, a higher incidence of mild vitreous liquefaction was found in
      group A than in group B. 4. PVD without collapsed vitreous (simple PVD) in both
      eyes was observed only in group A. 5. Our results indicated that the vitreous
      findings in both eyes of an individual were almost identical, and PVD may occur
      with less vitreous liquefaction in group A than in group B.

PMID- 8154385
TI  - [Preretinal vitreous liquefaction following fundus photocoagulation in young
      rabbits].
AB  - We examined the vitreous change after the retina was destroyed by
      photocoagulation. Multiple photocoagulation with continuous-wave xenon or diode
      laser was used to create coagulated spots with 5 disc diameters near the optic
      disc in 26 eyes of 13 pigmented rabbits aged four weeks. After clinical
      observation, the eyes were enucleated at 2 weeks and 3, 4, and 14 months after
      photocoagulation. The vitreous was stained with fluorescein and examined by
      slitlamp while immersed in water. The vitreous remained unchanged in 2 eyes at 2
      weeks after photocoagulation. A liquefied lacuna of the vitreous had formed
      anterior to the retinal scar in 20 eyes (83%) at 3, 4, and 14 months after
      photocoagulation. The liquefied lacuna assumed a columnar shape with its bottom
      corresponding to the retinal scar in 2 eyes at 14 months after photocoagulation.
      These results show that localized liquefaction in the posterior vitreous can be
      induced by fundus photocoagulation. It appeared that the presence of a normal
      retina is one of the prerequisites of integrity of the vitreous in young rabbit
      eyes.

PMID- 8154386
TI  - [Monocular indirect argon laser photocoagulation for advanced retinopathy of
      prematurity].
AB  - A retrospective study of monocular indirect argon laser retinal photocoagulation
      for retinopathy of prematurity (ROP) was performed on 53 eyes of 36 premature
      infants, admitted to the neonatal intensive care unit (NICU) of Juntendo hospital
      from Jan. 1988 to Dec. 1990. The argon laser beam was delivered from an argon
      laser source located in the outpatient clinic to the NICU through a 50-meter
      fiber-optic cable. Thirty-eight eyes of 27 infants showing stage 3 middle
      substage of ROP retained a mild grade of cicatrical ROP. Fifteen eyes of 8
      infants showed "Plus disease". Five eyes of these retained a severe grade of
      cicatrical ROP. The success rate of ROP treatment by laser photocoagulation was
      more satisfactory than in xenon are photocoagulation with cryotherapy. This
      method has slight technical difficulties, but the infants could be treated in a
      supine position in the incubators. Thus, monocular indirect argon laser retinal
      photocoagulation is a useful method in the treatment of ROP.

PMID- 8154387
TI  - [Thrombomodulin in diabetic retinopathy].
AB  - Thrombomodulin is a glycoprotein located on the surface membrane of vascular
      endothelial cells. Recently the presence of thrombomodulin antigens was detected
      in circulating blood plasma. The thrombomodulin antigens are thought to have been
      released from injured endothelial cells, and thus plasma thrombomodulin has been
      attracting attention as a new molecular marker indicating injuries to vascular
      endothelial cells. We investigated plasma thrombomodulin levels in relation to
      the severity of diabetic retinopathy, and found that they increased as
      retinopathy progressed. The Mann-Whitney U test revealed significant differences
      between no retinopathy and proliferative retinopathy (p = 0.002), between simple
      retinopathy and proliferative retinopathy (p = 0.01), and between
      preproliferative retinopathy and proliferative retinopathy (p = 0.03). However,
      ocular vascular injuries may correlate with systemic vascular injuries.
      Therefore, the progress of retinopathy may be predicted by monitoring plasma
      thrombomodulin levels in selected patients.

PMID- 8154388
TI  - [Serum adenosine deaminase and angiotensin converting enzyme activity in patients
      with endogenous uveitis].
AB  - Serum activity of adenosine deaminase (ADA) and angiotensin converting enzyme
      (ACE) was investigated in 32 patients with sarcoidosis, 22 patients with Behcet's
      disease, 22 patients with Vogt-Koyanagi-Harada's (VKH) disease and 253 healthy
      controls. In healthy controls, the ADA level was significantly higher in females
      than in males (p < 0.01). In patients with sarcoidosis, the serum ADA level was
      significantly higher in both males and females than in the controls (p < 0.01).
      In patients with Behcet's disease, the serum ADA level was significantly higher
      than in the controls (p < 0.01) in males only. In VKH disease, the serum ADA
      level showed no significant difference from the normal controls. Significant
      elevation of the serum ACE activity was observed only in patients with
      sarcoidosis (p < 0.01). Serum ACE activity was therefore considered to be more
      specific to sarcoidosis than serum ADA activity.

PMID- 8154389
TI  - [Effect of topical carbonic anhydrase inhibitor (MK-507) on intraocular pressure
      of normal human eyes].
AB  - The effects of topical carbonic anhydrase inhibitor (MK-507) on intraocular
      pressure (IOP) were studied in normal human eyes. The subjects were 6 normal
      volunteers. As a base line study, IOP and aqueous protein concentration
      determined by laser flare-cell photometry were examined from 0900 to 1800 hours.
      Then, the same time-course examinations were performed in the same subjects with
      an instillation of 1% MK-507 or administration of acetazolamide at a dose of 250
      mg on different days. MK-507 decreased IOP 2 hours after the instillation, and
      showed maximum reduction of IOP at 3 hours. MK-507 increased aqueous protein
      concentration 2 hours after the instillation, and reached its maximum
      concentration at 4 hours. Acetazolamide decreased IOP and increased aqueous
      protein concentration 1 hours after the administration. Maximum decrease of IOP
      was obtained at 1 hour after the administration of acetazolamide. An increase in
      aqueous protein concentration occurred at 1 hour after the administration, but
      its maximum increase was at 3 hours. Corneal thickness, anterior chamber depth,
      anterior chamber volume, and serum protein concentration were not affected by
      either drug treatment. These results suggest that the inhibition of aqueous humor
      formation causes the reduction of IOP seen in the use of MK-507.

PMID- 8154390
TI  - [VEPs induced by binocular disparity stimulus of the retinal nasotemporal
      overlap].
AB  - The human visual evoked potentials (VEPs) elicited by retinal disparity
      stimulation of the nasotemporal overlap area of the fundus, where ipsilaterally
      and contralaterally projecting retinal ganglion cells intermingle, were recorded
      bilaterally at the cortical hemispheres, and the contribution of the nasotemporal
      overlap to the mechanism of stereopsis was studied. The stimulus was a slit of a
      stereogram or correlogram applied to the center of the fovea of the right eye, or
      3 degrees or 6 degrees nasal or temporal to the fovea. The negative waves of the
      VEPs evoked by the stereogram were located at O1 and O2. The VEP amplitudes
      evoked by the stereogram markedly exceeded those by the correlogram. In comparing
      the VEP amplitude of O1 with that of O2, when the slit of the stereogram hit the
      nasal side of the nasotemporal overlap O1 exceeded O2, and on the temporal side,
      this was reversed. The difference between the amplitudes at O1 and O2 was
      significant at 3 degrees from the fovea. These results showed
      electrophysiologically that the width of the nasotemporal overlap in the human
      retina is more or less 4 degrees and that the activity from the overlap area
      converges to disparity selective neurons in the visual cortex, suggesting that
      the overlap area is the region where cues to depth perception are obtained in the
      front-posterior plane of the fixation point.

PMID- 8154391
TI  - [Event-related potentials in anisometropic amblyopia].
AB  - Event-related potentials were recorded from 20 neurologically normal children
      with anisometropic amblyopia. Stimulation was performed with an 'odd-ball'
      paradigm counting Randolts' circle, and in all cases N200 and P300 were recorded
      as event-related potentials. The latencies of N200 showed statistically
      significant delay (p < 0.001: Wilcoxson signed rank test), but P100 and P300 were
      not delayed in the stimulus input from amblyopic eyes. The degree of delay has no
      relationship with visual acuity or anisometropic differences. The results suggest
      that the cortical sensory processing functions represented by P300 were not
      damaged in the amblyopic cases observed in this study.

PMID- 8154392
TI  - [Sympathetic ophthalmia in an elderly man].
AB  - A 78-years-old man suffered from sympathetic ophthalmia. He had been treated with
      5-fluorouracil (5-FU) for metastasis of colon cancer in the liver. He received a
      perforating eye injury in the left eye thereafter the eye became phthisic. Two
      months after the injury, he noticed visual disturbance in the right eye. He was
      treated with large doses of systemic corticosteroid after a diagnosis of uveitis
      of the right eye, but the visual acuity of the right eye became worse. The eye
      showed non-specific diffuse uveitis. A diagnosis of sympathetic ophthalmia was
      made from previous history and ocular findings. We enucleated the injured eye and
      continued the systemic corticosteroid. Then the right eye improved.
      Histopathological examination of the enucleated eye revealed the choroid was
      infiltrated with a granulomatous lesion of lymphocytes and epithelioid cells. HLA
      typing showed DR4, DR8, DR52, DR53, and DQ1, and we made a final diagnosis of
      sympathetic ophthalmia. It is probable that the clinical findings were modified
      by the 5-FU treatment and the patient's advanced age.

PMID- 8154393
TI  - A family practice focus on prenatal care.

PMID- 8154394
TI  - Adaptability or extinction: trends in generalist and subspecialty medicine.

PMID- 8154395
TI  - The family physician and adolescent homosexuality.

PMID- 8154396
TI  - The family physician and adolescent homosexuality.

PMID- 8154397
TI  - The family physician and adolescent homosexuality.

PMID- 8154398
TI  - Violence in our public schools.

PMID- 8154399
TI  - Thyrotoxicosis and neurotoxic reaction to haloperidol.

PMID- 8154400
TI  - Treatment of stasis dermatitis and ulceration.

PMID- 8154401
TI  - Serotonergic drugs and the serotonin syndrome.

PMID- 8154402
TI  - Obsessive-compulsive disorder: a concealed diagnosis.
AB  - Epidemiologic data suggest that obsessive-compulsive disorder is the fourth most
      common mental disorder, after phobias, substance abuse and depression, and is
      nearly as common as asthma and diabetes mellitus. The understanding of obsessive
      compulsive disorder and its treatment have significantly improved over the past
      decade. Positron emission tomographic scanning has demonstrated characteristic
      changes in the cerebral metabolism of patients with obsessive-compulsive
      disorder. Selective serotonin reuptake inhibitors have been shown to alleviate
      the symptoms of this disorder. Treatment of obsessive-compulsive disorder
      includes drug therapy, behavior therapy and family therapy. The family physician
      can play a key role in recognizing the clinical markers of obsessive-compulsive
      disorder and negotiating a treatment plan that significantly lessens the
      psychosocial morbidity associated with it.

PMID- 8154403
TI  - Group A beta-hemolytic streptococcal pharyngitis: current clinical concepts.
AB  - The classic triad of fever, pharyngeal exudate and tender anterior cervical
      adenopathy is present in only 15 percent of cases of group A beta-hemolytic
      streptococcal pharyngitis. Since clinical findings are unreliable, a rapid
      streptococcal test or a throat culture should be performed to confirm the
      diagnosis. A positive rapid test immediately identifies group A beta-hemolytic
      streptococcus and may help encourage patients to complete the course of
      antibiotics. However, a negative rapid test does not definitively rule out this
      organism and should be followed by a throat culture. Early antibiotic therapy
      reduces the duration of pharyngitis, minimizes transmission and lessens
      complications such as acute rheumatic fever and abscess. A 10-day course of oral
      penicillin or an intramuscular injection of penicillin G benzathine is
      recommended. Erythromycin is recommended for patients who are allergic to
      penicillin.

PMID- 8154404
TI  - Evaluation of patients with suspected immunodeficiency.
AB  - Immunodeficiency diseases represent quantitative or qualitative defects in the
      normal immune response. Immunodeficiency should be suspected in patients who have
      recurrent or complicated infections. Conditions associated with secondary
      immunodeficiency should be ruled out by the history and physical examination,
      supplemented by routine laboratory tests. Functional analysis of the humoral,
      cell-mediated and phagocytic aspects of the immune system will reveal most
      immunodeficiency states. The therapeutic approach includes evaluation and
      treatment of all infections and, if possible, treatment of the immunologic
      defect.

PMID- 8154405
TI  - Evaluation and management of postdate pregnancy.
AB  - Postdate pregnancy (more than 42 weeks' gestation) accounts for about 10 percent
      of obstetric deliveries. Maternal and fetal assessment in anticipation of
      postdate pregnancy must begin early in the pregnancy. Gestational age must be
      accurately determined through judicious use of historical, physical and
      laboratory data. Familiarity with the physiologic changes associated with
      pregnancy, both near and after term, can help in predicting the possibility of
      neonatal morbidity from fetal macrosomia or dysmaturity, placental insufficiency
      and meconium-stained amniotic fluid. Management of the postdate pregnancy
      includes antenatal testing to measure fetal well-being. If testing indicates
      fetal distress or absent amniotic fluid, immediate delivery should be initiated.
      Cervical ripening should be considered if the Bishop score indicates an
      unfavorable chance of successful induction and if there is no need for immediate
      delivery. When labor commences after 42 weeks' gestation, continuous fetal
      monitoring is essential.

PMID- 8154406
TI  - A review of selected newer nonsteroidal anti-inflammatory drugs.
AB  - Development of nonsteroidal anti-inflammatory drugs (NSAIDs) with a goal of
      improved efficacy and lower toxicity has continued, resulting in the introduction
      of etodolac, ketorolac, nabumetone and oxaprozin on the market. Each of these
      agents appears to be as effective as other commonly used NSAIDs in the treatment
      of rheumatoid arthritis or osteoarthritis. Studies of nabumetone and etodolac
      show a lower incidence of serious gastrointestinal toxicity with both drugs, but
      additional large clinical trials are necessary to confirm these findings.
      Although ketorolac, which is now available in oral form, is an effective
      analgesic, its long-term use is limited by a high incidence of gastrointestinal
      toxicity. Oxaprozin is an effective, long-acting anti-inflammatory analgesic, but
      its comparative advantages remain undefined.

PMID- 8154407
TI  - Conditions of the skin. Recommended Core Educational Guidelines for Family
      Practice Residents. American Academy of Family Physicians.

PMID- 8154408
TI  - ACOG issues recommendations on exercise during pregnancy and the postpartum
      period.

PMID- 8154409
TI  - Nitroglycerin inhibits experimental thrombosis and reocclusion after
      thrombolysis.
AB  - Nitroglycerin inhibits platelet aggregation in vitro, but its effect on
      thrombosis and platelet function in vivo is controversial. This study assessed
      the effect of nitroglycerin on primary thrombus formation in response to vessel
      wall injury and secondary thrombus formation, or rethrombosis, after lysis of an
      existing thrombus. In the first protocol the right carotid artery was
      instrumented with a flow probe, stenosis, an anodal electrode, and a proximal
      infusion line. A 300 microA anodal current was used to induce endothelial injury
      and subsequent thrombotic occlusion of the vessel. Anisoylated plasminogen
      streptokinase activator complex (APSAC; 0.05 U/kg intraarterially) was injected
      proximal to the thrombus 30 minutes after occlusion. After APSAC, nitroglycerin
      (1 microgram/kg/min intraarterially, n = 7) or vehicle (n = 6) was infused
      proximal to the thrombus for 3 hours. Reocclusion occurred in two of seven
      nitroglycerin-treated dogs and six of six vehicle-treated dogs (p < 0.05). In the
      second protocol both carotid arteries were instrumented as described previously.
      Anodal current (300 microA, 180 minutes) was applied to the right carotid (n =
      12) artery to determine control times to occlusion. The left carotid artery
      served as the test vessel, receiving either nitroglycerin (1 microgram/kg/min
      intraarterially, n = 6) or trimethaphan (0.05 mg/kg/hr intraarterially, n = 6).
      Trimethaphan was used to produce controlled hypotension to match the
      approximately 10% decrease in mean arterial blood pressure that was observed
      during nitroglycerin infusion. Control arteries and those treated with
      trimethaphan formed occlusive thrombi in all instances. Nitroglycerin infusion
      resulted in a lower incidence of occlusion (1 of 6; p < 0.05 vs control value)
      and inhibited ex vivo platelet aggregation to adenosine diphosphate and
      arachidonic acid (p < 0.05). Local infusion of nitroglycerin reduced the
      formation of primary thrombi, independent of the hypotensive effect of the drug,
      and exerted systemic effects on platelet aggregation. Furthermore, platelet
      inhibition with nitroglycerin reduced the incidence of secondary thrombus
      formation (rethrombosis) after thrombolysis. The results suggest that a potential
      benefit of nitroglycerin therapy may be derived from its ability to inhibit
      thrombotic events in patients with unstable angina or myocardial infarction.

PMID- 8154410
TI  - Prostaglandin E1 does not accelerate rTPA-induced thrombolysis in acute
      myocardial infarction.
AB  - Fifteen patients who arrived between 6 and 24 hours after the onset of acute
      myocardial infarction and who were found to have totally occluded coronary
      arteries, received aspirin, heparin, and tissue plasminogen activator given over
      3 hours. Eight patients were randomly assigned to receive intravenous
      prostaglandin E1, 20 ng/kg/min for 6 hours, while seven patients received placebo
      infusion. Coronary arteriography begun immediately before the start of tissue
      plasminogen activator and repeated every 15 minutes revealed restoration of
      antegrade flow in two of eight (25%) patients treated with prostaglandin E1 and
      in two of seven (28%) patients receiving placebo. Pharmacologic sampling of
      tissue plasminogen activator levels were performed at baseline and 30, 45, 60,
      75, 90, 135, 180, 190, 210, and 240 minutes afterwards for assessment of tissue
      plasminogen activator antigen. There was no difference in fibrinogen levels and
      no difference in tissue plasminogen activator antigen levels at these time
      periods. Clearance values of tissue plasminogen activator were calculated and
      were not different between the two groups. These data do not support the use of
      prostaglandin E1 for the acceleration of reperfusion in patients receiving tissue
      plasminogen activator for acute myocardial infarction.

PMID- 8154411
TI  - Is the reduction of myocardial infarct size by dietary fish oil the result of
      altered platelet function?
AB  - Sprague-Dawley rats fed a diet containing 12% fish oil (18% eicosapentaenoic acid
      [EPA] and 12% docosahexaenoic acid [DHA]), for 1 week (group I, n = 9) or 8 weeks
      (group III, n = 42) and controls (group II, n = 8; group IV, n = 36,
      respectively) were subjected to 35 minutes of left coronary artery occlusion
      followed by 120 minutes of reperfusion. Compared to the controls, infarct size
      was significantly reduced in group III (15% +/- 2%, n = 42 vs 34% +/- 4%, n = 36;
      p < 0.001; infarct mass/risk area x 100%), but no change in group I (39% +/- 5%,
      n = 9 vs 35% +/- 5%, n = 8; p = not significant). Bleeding time was prolonged in
      group III (290 +/- 73 sec) compared to group IV (99 +/- 10 sec, p = 0.015). Omega
      3 fatty acid (EPA and DHA) levels in platelets were significantly higher in the
      rats fed 8 weeks of fish oil (group III) compared to the controls (group IV) and
      the rats fed 8 weeks of fish oil and then a regular diet until bleeding time
      normalized (group V) (7.2% +/- 0.6% vs 1.2% +/- 0.2% and 4.9% +/- 0.5%; 3.8% +/-
      0.7% vs 1.8% +/- 0.3% and 2.8% +/- 0.6%, p < 0.001 and 0.05, respectively). These
      data indicate that long-term (8 weeks) dietary fish oil supplementation
      significantly reduces infarct size; short-term (1 week) does not. This reduction
      of infarct size appears to correlate with altered platelet function and EPA and
      DHA levels in platelets.

PMID- 8154412
TI  - Effects of captopril therapy after late reperfusion on left ventricular
      remodeling after experimental myocardial infarction.
AB  - Reperfusion that is too late to salvage ischemic myocardium reduces early infarct
      expansion, and captopril therapy favorably alters long-term left ventricular
      remodeling. To study whether the beneficial effects of these two therapies are
      additive, we examined the effects of captopril therapy after late reperfusion on
      left ventricular remodeling after acute myocardial infarction. Female Sprague
      Dawley rats (n = 67) were randomly assigned to one of four groups: group 1, sham
      surgery and no treatment; group 2, left coronary artery ligation and no treatment
      (myocardial infarction [r MI]); group 3, left coronary artery ligation,
      reperfusion 2 hours later, and no treatment (late reperfusion [LR]); and group 4,
      left coronary artery ligation, reperfusion 2 hours later, and captopril treatment
      (LR-Cap). Captopril therapy (2 gm/L of drinking water) was begun in the LR-Cap
      group in the immediate post-operative period and continued for 20 days. Twenty
      one days postoperatively, hemodynamic measurements were made before and after
      volume loading. The rats were killed, their hearts were removed, and passive
      pressure-volume curves were obtained. The hearts were then fixed at a constant
      pressure for morphometric analysis. Compared with the MI group, the LR group had
      a lower expansion index and a higher thinning ratio. There were no differences in
      hemodynamics, left ventricular volumes, or other morphometric indexes between the
      two groups. Compared with the MI and LR groups, the LR-Cap group had lower peak
      left ventricular end-diastolic pressure, lower left ventricular volume, lower
      left and right ventricular weights, and a leftward shift of pressure-volume
      curves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154413
TI  - Effects of metoprolol on early infarct expansion after acute myocardial
      infarction.
AB  - The effects of metoprolol on early infarct expansion after acute myocardial
      infarction were studied in rats (n = 54) that underwent either left coronary
      artery ligation (MI) or sham operation. Immediately after surgery, the rats
      received either metoprolol (M) by mouth, which had been dissolved in drinking
      water, for 72 hours supplemented with three intraperitoneal doses over the first
      24 hours or no treatment (H2O). Three days after the initial surgery, hemodynamic
      measurements were made before and after volume loading. The rats were killed, the
      hearts were removed, and passive pressure-volume curves were obtained. The hearts
      were then fixed at a constant pressure and analyzed morphometrically. Infarct
      size was nonsignificantly lower in the metoprolol-treated group compared with the
      untreated group (38% +/- 5% MI-M vs 48% +/- 3% MI-H2O, p = 0.10) Compared with
      infarcted untreated rats, infarcted metoprolol-treated rats had a lower heart
      rate (322 +/- 13 beats/min MI-M vs 452 +/- 19 beats/min MI-H2O, p < 0.001), lower
      left ventricular systolic pressure (63 +/- 4 mm Hg MI-M vs 90 +/- 6 mm Hg MI-H2O,
      p = 0.004), and lower +dp/dt (1340 +/- 169 mm Hg/sec MI-M vs 2872 +/- 273 mm
      Hg/sec MI-H2O, p < 0.001), but left ventricular end-diastolic pressure and
      cardiac index did not differ between the two groups. Left ventricular weight
      corrected for body weight was higher in infarcted rats treated with metoprolol
      compared with infarcted untreated rats (2.76 +/- 0.07 gm/kg MI-M vs 2.41 +/- 0.09
      gm/kg MI-H2O, p < 0.05). The initial slope of the pressure-volume relationship
      Ki, an index of operative volume stiffness, was lower in infarcted rats treated
      with metoprolol compared with infarcted untreated rats (p = 0.03). There were,
      however, no significant differences in the expansion index, thinning ratio, or
      left ventricular volume between the two infarcted groups. Thus metoprolol therapy
      begun in the immediate postinfarction period promotes an increase in left
      ventricular weight and reduces operative volume stiffness but has no significant
      effect on indexes of early infarct expansion.

PMID- 8154414
TI  - Plasma neuropeptide Y levels in the acute and early convalescent phase after
      myocardial infarction.
AB  - The sympathetic nervous system is activated in acute myocardial infarction (MI).
      Scarce data exist, however, regarding the release of the sympathetic
      cotransmitter neuropeptide Y (NPY) during the acute and early convalescent phases
      after acute MI. Plasma NPY determination was obtained on days 1 and 3 after
      admission from 47 patients with acute MI and from eight control patients with
      acute chest pain without MI. Samples were also obtained on day 30 from the 39
      survivors from the original MI cohort. Plasma NPY peaked on day 3 in the MI group
      (day 1: mean = 46.0 pmol/L, SEM = 6.4 pmol/L; day 3: mean = 60.8 pmol/L, SEM =
      5.7 pmol/L; day 30: mean = 27.2 pmol/L, SEM = 4.1 pmol/L; days 1 to 3: p = 0.002;
      days 3 to 30: p < 0.001), whereas in the control group a nonsignificant decrease
      from day 1 (mean = 42.6 pmol/L, SEM = 12.3 pmol/L) to day 3 (mean = 34.0 pmol/L,
      SEM = 5.6 pmol/L) was observed. Plasma NPY levels were significantly increased in
      patients with MI on day 3 (p = 0.044), but not at baseline compared with the
      control group. No significant association between plasma NPY and plasma
      catecholamines, clinical heart failure, or 1-month survival was evident. These
      results suggest that increased plasma levels of the vasoconstrictory and
      cardiodepressant sympathetic neurotransmitter NPY are present in the recovery
      phase of MI, but with a plasma profile distinct from that of catecholamines.

PMID- 8154415
TI  - Use of sequential teboroxime imaging for the detection of coronary artery
      occlusion and reperfusion in ischemic and infarcted myocardium.
AB  - Nine Yorkshire pigs underwent coronary artery occlusion followed by 2 hours of
      reperfusion. In five pigs (group A) the occlusion time was 15 minutes and in four
      pigs (group B) the occlusion time was 1 hour. Teboroxime was administered and
      images were acquired at baseline, and following occlusion and reperfusion.
      Infarct size was determined by triphenyl tetrazolium staining. Normalized
      regional myocardial blood flow, as determined by radio-labeled microspheres, was
      0.26 +/- 0.09 following occlusion and 0.83 +/- 0.07 following reperfusion (p <
      0.01). Significant differences were found between the defect/normal scan ratios
      on the baseline and occlusion scans (1.0 +/- 0.03 vs 0.54 +/- 0.10; p < 0.01) and
      between the occlusion and reperfusion scans (0.54 +/- 0.10 vs 0.97 +/- 0.17; p <
      0.01). This is the first study to demonstrate that rapid sequential teboroxime
      imaging can detect acute coronary occlusion and reperfusion to both ischemic and
      infarcted myocardium. Teboroxime may be an excellent tracer for the early
      evaluation of infarct artery patency in patients receiving thrombolytic therapy.

PMID- 8154416
TI  - Myocardial viability: fluorine-18-deoxyglucose positron emission tomography in
      prediction of wall motion recovery after revascularization.
AB  - To assess the value of positron emission tomography (PET) imaging with fluorine
      18-deoxyglucose ([18F]FDG) in predicting cardiac wall motion recovery after
      revascularization, 48 consecutive patients with previous myocardial infarction
      were studied. The normalized [18F]FDG uptake at rest was assessed
      semiquantitatively and compared to perfusion at rest as studied by SPECT imaging.
      Wall motion was analyzed with echocardiography before and after
      revascularization. Wall motion recovery occurred in 27 (30%) of the
      revascularized 90 dysfunctional segments. Preserved [18F]FDG uptake (mean +/- 2
      SD) was commonly found in dysfunctional segments, but only 54% of these segments
      recovered after revascularization. Subnormal [18F]FDG uptake identified
      accurately the segments with no potential to recover (predictive value 100%). By
      using an optimized threshold value for normalized [18F]FDG uptake, the
      sensitivity of 85% and specificity of 84% to predict functional recovery were
      reached simultaneously. However, in the segments with moderately or severely
      reduced perfusion at rest, the diagnostic accuracy of [18F]FDG uptake for
      viability was 100%. The results of this study show that the presence of viable
      tissue indicated by preserved [18F]FDG uptake does not inevitably imply
      functional recovery after revascularization. However, acceptable diagnostic
      accuracy for viability might be reached by [18F]FDG alone, providing that
      appropriate uptake limits are used. The combined evaluation of [18F]FDG uptake
      and perfusion enables precise assessment of myocardial viability.

PMID- 8154417
TI  - Prevalence of right ventricular perfusion defects after inferior myocardial
      infarction assessed by low-level exercise with technetium 99m sestamibi
      tomographic myocardial imaging.
AB  - To assess the prevalence of right ventricular perfusion defects after a recent
      inferior wall myocardial infarction, 33 patients were studied 6 to 14 days after
      infarction with low-level exercise testing and technetium 99m (99mTc) sestamibi
      (SPECT) imaging. Twenty-two control subjects with a < 5% likelihood of coronary
      artery disease undergoing exercise 99mTc sestamibi imaging were also studied. For
      each image the right ventricle was computer isolated from reconstructed
      transverse cardiac slices, followed by reorientation into oblique slices. Both
      right and left ventricular images were visually assessed for defects. A
      quantitative method of defect detection was also applied to the right ventricle.
      For the right ventricle, 100% of the stress images and 96% of the rest images
      were adequate for interpretation. Right ventricular stress perfusion defects were
      identified in 10 (30%) of 33 patients with recent inferior infarction, with 50%
      completely or partially normalizing on rest images, consistent with ischemia. Of
      14 patients with left ventricular inferoseptal defects, eight (57%) had right
      ventricular defects compared with 2 (11%) of 19 without inferoseptal defects (p <
      0.005). We concluded that the right ventricle can be adequately assessed for
      perfusion defects by means of exercise with 99mTc sestamibi SPECT imaging.
      Defects of the right ventricle after inferior myocardial infarction occur
      frequently, and many have evidence of ischemia. Right ventricular perfusion
      defects are closely associated with left ventricular inferoseptal defects.

PMID- 8154418
TI  - Does myocardial perfusion scintigraphy demonstrate clinical usefulness in
      patients with markedly positive exercise tests? An assessment of the method in a
      high-risk subset.
AB  - To evaluate the clinical utility of perfusion scintigraphy in patients with
      markedly positive exercise ECGs, we studied 94 consecutive patients with markedly
      positive exercise ECGs; 74 of them were also studied with scintigraphy. Patients
      undergoing scintigraphy had an intermediate pretest likelihood of coronary
      disease and were divided into two groups: those with reversible defects involving
      one complete area or aspects of multiple vascular areas (group 1, 38 patients),
      and those with normal scintigrams and reversible defects in a limited aspect of
      one vascular area, isolated fixed defects, or both (group 2, 36 patients). Among
      all demographic and exercise variables, only a hypotensive or blunted blood
      pressure response and scintigraphic lung uptake or cavitary dilation, although
      insensitive, were more frequent in group 1 (all p < 0.05). All 36 patients in
      group 1 and 14 of 18 in group 2 who underwent coronary angiography had
      significant coronary lesions; 31 in group 1 but only seven in group 2 had
      multivessel disease (p < 0.05). Subsequently 32 patients in group 1 had
      revascularization compared with only two patients in group 2. Only one cardiac
      event was noted among 34 patients in group 2 who were followed for a mean of 38
      months while they were being treated medically. However, four of nine patients in
      group 1 initially treated medically required late revascularization because of
      clinical progression of disease, and one patient died (p < 0.05). Compared with
      patients having scintigraphy, patients not imaged had a higher pretest likelihood
      of coronary disease, a higher incidence of angina, unstable angina, and induced
      angina, with a lower exercise time and time to ST depression (p < 0.05). All
      underwent angiography, and 16 had multivessel disease. Not all patients with
      markedly positive exercise ECGs were at similarly high coronary risk. Some with
      high-risk coronary anatomy were identified without the use of scintigraphy. In
      others, where diagnosis and prognosis were less clear, scintigraphy aided in the
      diagnosis and accurately identified a low-risk subgroup as did no other
      parameter.

PMID- 8154419
TI  - Effects of aminophylline on cardiac function and regional myocardial perfusion:
      implications regarding its antiischemic action.
AB  - Aminophylline improves exercise capacity in patients with angina. Because this
      drug does not dilate epicardial coronary vessels, its beneficial effect is from
      either a reduction of myocardial oxygen consumption or an improvement of
      myocardial blood flow distribution. This study was performed to assess the
      effects of aminophylline on cardiac function and on regional myocardial perfusion
      to establish the mechanisms of its antiischemic action. In 10 patients during
      cardiac catheterization hemodynamic parameters and cardiac volumes were obtained
      during baseline and after intravenous infusion of aminophylline. Aminophylline
      decreased left ventricular end-diastolic pressure (from 11 +/- 4 to 4 +/- 2 mmHg,
      p < 0.001), mean right atrial pressure (from 5 +/- 2 to 2 +/- 1 mmHg, p < 0.01),
      and left ventricular end-diastolic volume (from 117 +/- 36 to 88 +/- 36 ml, p <
      0.01); it increased peak dp/dt (from 1931 +/- 329 to 2430 +/- 540 mmHg/sec, p <
      0.001) and heart rate (from 69 +/- 9 to 76 +/- 14 beats/min, p < 0.05) and did
      not modify systolic aortic pressure (138 +/- 14 vs 137 +/- 16 mmHg, p = not
      significant [NS]). Estimated oxygen consumption during aminophylline (6.7 +/- 1.3
      ml/min/gm) was similar to that during baseline (6.7 +/- 1.4 ml/min/gm). In
      another study in nine anesthetized dogs with a critical stenosis of the left
      anterior descending artery, myocardial perfusion was assessed by microspheres
      during control atrial pacing and during atrial pacing after aminophylline; left
      atrial pressure was kept constant throughout the study.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8154420
TI  - Prognostic significance of left ventricular aneurysm in the Cardiac Arrhythmia
      Suppression Trial (CAST) population.
AB  - Left ventricular aneurysm has been associated with increased mortality rates. The
      Cardiac Arrhythmia Suppression Trial (CAST) database was used prospectively to
      assess (1) the prognostic significance of left ventricular (LV) aneurysm after
      myocardial infarction on mortality rates and (2) the relation of LV aneurysm to
      ventricular arrhythmias and their suppressibility. All patients in the CAST study
      were enrolled after myocardial infarction. They had > or = 6 ventricular
      premature depolarizations (VPDs) per hour and ejection fraction < or = 55%; they
      were enrolled in the study an average of 96 days after the index myocardial
      infarction. Of 2494 patients with wall motion data, 164 had LV aneurysm, 600 had
      only dyskinesis, 913 had only akinesis, and 817 had none of these. Radionuclide
      scan was used in 39%, two-dimensional echocardiography in 30%, and LV angiogram
      in 31%. Baseline VPDs and nonsustained ventricular tachycardia were similar in
      all groups. LV aneurysm patients were more frequently eliminated during open
      label titration. The incidence of sustained VT during follow-up was only 2.8% for
      aneurysm patients, a rate that was similar to the other groups. Patients with LV
      aneurysm had significantly lower survival rates (82% vs 91%) at 16 months after
      study entry than those without these wall motion abnormalities (p < 0.005). When
      survival rates were adjusted for ejection fraction there was still a moderately
      large hazard ratio (1.34) of LV aneurysm that was not statistically significant
      (p = 0.18). We conclude that (1) the presence of LV aneurysm does not
      independently worsen prognosis, and (2) older concepts of LV aneurysm and
      ventricular arrhythmias must be reevaluated.

PMID- 8154421
TI  - Activation times in and adjacent to reentry circuits during entrainment:
      implications for mapping ventricular tachycardia.
AB  - Myocardial infarct scars giving rise to reentrant ventricular tachycardia can
      contain "bystander" areas of abnormal electrical activity that are difficult to
      distinguish from reentry circuit sites. Pacing to entrain ventricular tachycardia
      with analysis of electrograms at the pacing site is useful to identify reentry
      circuit sites but assumes that electrograms reflect activation times at the
      recording site. The purpose of this study was to determine whether a similar
      analysis could be applied to electrograms recorded from sites distant from the
      pacing site. In computer simulations, activation times at sites in and adjacent
      to figure-eight reentry circuits were analyzed during entrainment of tachycardia
      by pacing at various sites. During entrainment, activation at reentry circuit
      sites activated by the stimulated orthodromic wavefronts maintains the same
      relation to the QRS complex as that during tachycardia. The return cycle from the
      last entrained electrogram to the following electrogram equals the tachycardia
      cycle length. The same findings occur, however, at bystander sites activated by
      stimulated wavefronts that have propagated orthodromically through the circuit.
      When a reentry circuit site is activated by stimulated antidromic wavefronts, the
      electrogram to QRS interval is shorter than that during tachycardia, the return
      cycle may be less than the tachycardia cycle length, and the site may appear to
      be dissociated from the tachycardia, despite its location in the circuit. If the
      entrained electrogram to QRS interval exceeds the tachycardia electrogram to QRS
      interval and the return cycle length exceeds the tachycardia cycle length, it is
      likely that both pacing and recording sites are outside the reentry circuit.
      Thus, during entrainment, failure to dissociate an electrogram from the QRS
      complex and the return cycle length does not reliably indicate the relation of
      the recording site to the reentry circuit when the recording and pacing sites are
      separate.

PMID- 8154422
TI  - Is transthoracic impedance arrhythmia specific? Experimental studies.
AB  - Transthoracic impedance (TTI) is a major determinant of current flow in
      defibrillation, and it is therefore important to understand the factors that
      determine TTI. Our purpose was to evaluate the effect of atrial and ventricular
      arrhythmias on TTI. In anesthetized, closed-chest dogs we measured TTI by means
      of a technique previously validated by us, which did not require administration
      of actual shocks. Measurements were made at baseline (sinus rhythm) and during
      rapid atrial pacing (atrial fibrillation), rapid ventricular pacing, and
      electrically induced ventricular fibrillation (VF) with respiration discontinued.
      TTI was unchanged by rapid atrial or ventricular pacing. When VF was induced and
      respiration was discontinued, TTI fell immediately from 51.6 +/- 4.3 ohms to 45.6
      +/- 4.7 ohms (p < 0.01) and did not change thereafter. The drop in TTI was
      probably due to respiratory arrest and decreased chest size with full exhalation;
      when VF was induced but respiration was continued TTI did not change, whereas
      discontinuing respiration caused TTI to fall even if VF was not induced. We
      conclude that TTI is not altered by arrhythmias.

PMID- 8154423
TI  - Usefulness of oral quinidine-mexiletine combination therapy for sustained
      ventricular tachyarrhythmias as assessed by programmed electrical stimulation
      when quinidine monotherapy has failed.
AB  - In patients presenting with sustained ventricular tachyarrhythmias, when oral
      quinidine monotherapy fails as determined by programmed electrical stimulation,
      the degree of benefit observed with combination therapy with mexiletine is
      debated. We prospectively studied 20 consecutive patients (16 men and 4 women)
      aged 33 to 77 years (mean age, 62 +/- 11 years) who were treated with maximally
      tolerated quinidine and mexiletine combination therapy and who had ventricular
      tachyarrhythmias induced at baseline and during oral quinidine monotherapy.
      Coronary artery disease was present in 19 patients (95%). Programmed electrical
      stimulation was performed at 2 drive train cycle lengths with up to 3
      extrastimuli at two ventricular sites. During follow-up study with combination
      quinidine-mexiletine therapy ventricular tachyarrhythmias were rendered
      noninducible in four patients (20%). The remaining 16 patients showed a
      significant slowing of their tachycardia cycle length (267 +/- 56 msec baseline
      vs 320 +/- 75 msec with quinidine vs 345 +/- 53 msec with combination therapy, p
      < 0.05). There was also an increase in the mean QTc interval (452 +/- 50 msec
      baseline vs 477 +/- 79 msec after quinidine vs 486 +/- 65 msec with combination
      quinidine-mexiletine therapy, p = not significant) and in the mean ventricular
      effective refractory period (246 +/- 25 msec baseline vs 281 +/- 37 msec after
      quinidine vs 290 +/- 25 msec with combination quinidine-mexiletine therapy, p <
      0.05). We conclude that sustained ventricular tachyarrhythmias induced during
      quinidine monotherapy were rendered noninducible by oral combination therapy with
      quinidine-mexiletine in 20% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154424
TI  - Advanced radiofrequency catheter ablation in canine myocardium.
AB  - Current radiofrequency (RF) ablation technology is limited by small lesion size.
      To enhance the size of RF-induced left ventricular (LV) endocardial lesions, we
      evaluated the effects of an enlarged distal electrode tip and increased RF power
      on lesion volume. Steerable electrode catheters with distal electrode tips of 4
      to 12 mm were studied in anesthetized dogs at power settings of 20 to 100 W.
      Temperature was continuously monitored from a thermistor located at the tip of
      the catheter. RF energy (500 kHz, unmodulated) was applied between the tip of the
      catheter and a large skin electrode at four separate LV sites in each animal.
      Hearts were excised, frozen, sectioned, and stained with nitroblue tetrazolium.
      Lesion area was planimetered and volume was calculated. Lesion volume increased
      with increasing electrode size and delivered power. However, a rise in impedance
      limited maximal lesion size at higher power with each electrode. Maximal lesion
      size with an 8 mm tip was approximately twice the size of the maximal lesion with
      a 4 mm tip (914 +/- 362 mm3 vs 460 +/- 150 mm3, p < 0.01). Minimal lesions were
      seen with large tip electrodes at power < 40 W because of low tip temperature (<
      55 degrees C). Average tip temperature correlated with measured lesion volume (r
      = 0.7). Ventricular fibrillation occurred in approximately one half of the
      animals studied, and was associated with larger lesion volume (p < 0.01).
      Catheter ablation of ventricular tachycardia may be enhanced by this technology.

PMID- 8154425
TI  - Absence of hemodynamic tolerance to nicorandil in patients with severe congestive
      heart failure.
AB  - To evaluate whether hemodynamic tolerance develops to nicorandil, a nitrate and
      potassium channel opener, 14 patients with chronic heart failure (CHF) were
      treated with nicorandil and 11 were treated with nitroglycerin (GTN). Doses of
      GTN or nicorandil were titrated to achieve a > or = 20% reduction in pulmonary
      capillary wedge pressure (PCWP) within 1 hour, and the infusion was maintained at
      a constant rate for 24 hours. Both groups of patients had comparable hemodynamic
      parameters before drug infusions were started. The fall in PCWP was identical
      after 1 hour infusion of either GTN or nicorandil. In the GTN group, PCWP was not
      significantly different from the baseline value at 12 hours; however, in the
      nicorandil group, PCWP remained significantly lower than the preinfusion value
      for 24 hours. During the study period changes in plasma atrial natriuretic
      peptide (ANP) concentrations paralleled and correlated with changes in PCWP (r =
      0.84, p < 0.001). These findings indicate that CHF patients develop hemodynamic
      tolerance to GTN within 12 hours of continuous infusion, but not to nicorandil,
      which remained hemodynamically effective during the 24-hour period of infusion.
      Furthermore, plasma ANP concentration may be a useful noninvasive index of
      hemodynamic tolerance during GTN or nicorandil therapy in patients with CHF.

PMID- 8154426
TI  - Divergent effects of intravenous dobutamine and nitroprusside on left atrial
      contribution to ventricular filling in dogs with chronic heart failure.
AB  - The left atrial (LA) contribution to left ventricular (LV) filling is often
      attenuated in patients with heart failure. It remains uncertain, however, whether
      therapy with positive inotropic agents or vasodilators improves or further
      impairs this maladaptation. In the present study, the effects of intravenous
      dobutamine and nitroprusside on the LA contribution to LV filling was examined in
      seven dogs with chronic heart failure produced by multiple sequential
      intracoronary microembolizations. Pulsed Doppler echocardiography was used to
      measure mitral inflow velocity before and after an intravenous infusion of
      dobutamine (4 micrograms/kg/min) and an intravenous infusion of nitroprusside (3
      micrograms/kg/min). The percent LA contribution to LV filling was calculated as
      the ratio of the time-velocity integral of the LA component of mitral inflow
      velocity (Ai) to the time-velocity integral of total diastolic inflow velocity
      (Ti) times 100. Dobutamine increased LV filling pressure, LV end-diastolic wall
      stress, LV end-diastolic stiffness, and Ei, but had no effect on Ai or the
      percent LA contribution to filling (14% +/- 3% vs 12% +/- 2%) (p < 0.34). In
      contrast, nitroprusside decreased LV filling pressure, LV end-diastolic wall
      stress, and end-diastolic stiffness, and increased Ei, Ai, and the percent LA
      contribution to LV filling (12% +/- 2% vs 17% +/- 2%) (p < 0.01). The results
      indicate that dobutamine and nitroprusside have divergent effects on the LA
      contribution to LV filling. In dogs with chronic heart failure, dobutamine
      appears to impair LA contribution to the LV filling by augmenting LA workload,
      whereas nitroprusside appears to elicit greater LA contribution to LV filling by
      reducing the LA workload.

PMID- 8154427
TI  - Significance of left atrial spontaneous echo contrast in rheumatic mitral valve
      disease as a predictor of systemic arterial embolization: a transesophageal
      echocardiographic study.
AB  - The association between left atrial spontaneous echo contrast (SEC) and a history
      of systemic arterial embolization was evaluated in 359 consecutive patients with
      rheumatic mitral valve disease during a 3-year period. All patients underwent
      transesophageal echocardiographic (TEE) and cardiac catheterization studies. Of
      these, 207 patients had predominant mitral stenosis, 55 had significant mitral
      regurgitation, and the remaining 97 with xenograft mitral valve replacement
      developed valvular dysfunction (32 resulted in predominant mitral stenosis and 65
      in significant mitral regurgitation). Left atrial SEC was detected in 108
      patients (group A) and was absent in 251 (group B). Group A patients showed a
      higher frequency of left atrial thrombi or history of previous embolization than
      those in group B (59.3% vs 7.2%; p < 0.001). Group A patients also had a higher
      frequency of recent (< or = 1 week before TEE study) and remote (> 1 week before
      TEE study) embolization than did group B patients (recent: 19.4% vs 2.8% [p <
      0.001]; remote: 13.0% vs 4.0% [p < 0.001]). Multivariate analysis showed that
      left atrial SEC (p = 0.01) was the only independent predictor of systemic
      arterial embolization. It is concluded that patients with left atrial SEC had a
      significantly higher risk for thromboembolism, and TEE is a useful modality to
      identify this subset of patients with rheumatic mitral valve disease.

PMID- 8154428
TI  - The left atrial volume curve can be assessed from pulmonary vein and mitral valve
      velocity tracings.
AB  - After instantaneous left atrial volume was defined as the net difference between
      the forward-flowing blood from the lungs and the blood flowing through the mitral
      valve, we constructed the left atrial volume curve by sampling the Doppler mitral
      valve and the right upper pulmonary vein velocity from an apical four-chamber
      view in eight normal subjects and 11 patients with heart disease. The
      instantaneous mitral valve flow was estimated as mitral valve velocity x annular
      area (derived from the same view), whereas the pulmonary venous flow was obtained
      as right upper pulmonary vein velocity x pulmonary vein area, where pulmonary
      vein area = mitral valve velocity integral x mitral valve area) divided by
      pulmonary vein velocity integral. The left atrial volume curve can then be
      derived as: [(instantaneous pulmonary venous flow - mitral valve flow) + left
      atrial volume assessed at end diastole by two-dimensional echocardiography].
      Biplane angiographic left atrial volume curves, available in four of 11 patients,
      compared morphologically very closely with the noninvasive curves, whereas the
      correlation coefficient for maximum (end-systolic) and filling (maximum minus
      minimum) left atrial volumes obtained from the Doppler-derived curve and the
      corresponding two-dimensional echocardiographic estimates was 0.95 (p < 0.001,
      standard error of the estimate = 11.9 ml), the dispersion of the data increased
      with decreasing volumes. These data demonstrate that combined Doppler mitral
      valve and pulmonary vein velocities can be used to construct the left atrial
      volume curve in human beings. The approach described, besides providing a tool
      for further noninvasive evaluation of the left atrial function, offers the
      opportunity for relating the continuous pulmonary venous flow to the intermittent
      filling of the ventricle through the mitral orifice in diastole, underlining the
      complex role that the left atrial cavity plays in this process.

PMID- 8154429
TI  - Echocardiographic findings in 104 professional cyclists with follow-up study.
AB  - To assess the effect of long-term athletic training on the heart, 104
      professional cyclists and 40 sedentary controls (69 younger cyclists and 26
      controls aged 20 to 39 and 35 older cyclists and 14 controls aged 40 to 60) were
      examined by using M-mode and pulsed Doppler echocardiography. Cyclists had larger
      and more hypertrophied left ventricle than did controls (p < 0.001) and had
      normal percentages of fractional shortening (%FS). The ratio of left ventricular
      late-to-early diastolic peak filling velocity (A/R) of younger cyclists was
      normal, but the A/R of older cyclists was larger than that of controls (p <
      0.001). Of the 104 cyclists, 95 continued cycling and were reexamined 2 years
      later; 9 of 40 older cyclists retired and were reexamined 20 +/- 8 months after
      retirement. During the follow-up period for the active cyclists, left ventricular
      dilatation, hypertrophy, and %FS of both younger and older cyclists and the A/R
      of younger cyclists did not change. However, the A/R of older cyclists increased
      (p < 0.01). For the nine retired cyclists, left ventricular dimension decreased
      (p < 0.001), left ventricular wall thickness and %FS did not change, and A/R
      increased (p < 0.05) after retirement. We concluded that (1) cyclists had large
      and hypertrophied left ventricles with normal systolic function, and (2) some
      cyclists with long-term athletic training may have partly irreversible left
      ventricular hypertrophy with impaired left ventricular diastolic filling.

PMID- 8154430
TI  - Doppler echocardiographic evaluation of the spectrum of left ventricular
      diastolic dysfunction in essential hypertension.
AB  - Left ventricular topography and diastolic and systolic functions were studied in
      41 patients with essential hypertension (group 1) and 33 age-matched normal
      adults (group 2) by Doppler echocardiography. In group 1 54% had LV concentric
      hypertrophy, 19% had combined concentric hypertrophy and eccentric remodeling,
      and 27% had concentric remodeling. LV systolic function was within the normal
      range. In concentric LV remodeling, the EDV was significantly decreased (compared
      with group 2) (84 +/- 15 vs 130 +/- 38 ml, p < 0.05), whereas the NPFR was normal
      (2.89 +/- 0.65 vs 3.22 +/- 0.83 sec-1, p = NS). In concentric hypertrophy, LV end
      diastolic and end-systolic volumes were normal, but the NPFR was decreased (2.04
      +/- 0.59 sec-1). Patients with concentric hypertrophy and eccentric remodeling
      had the largest end-diastolic (140 +/- 48 ml) and end-systolic (62 +/- 32 ml)
      volumes and the lowest NPFR (1.67 +/- 0.69 sec-1). The LVMI inversely correlated
      with the NPFR (r = -0.89, p < 0.0001). Thus LV concentric hypertrophy with or
      without concentric or eccentric remodeling is seen in patients with systemic
      hypertension. A decrease in peak filling occurs early in the evolution of
      hypertensive heart disease and is observed even when systolic performance is
      still normal.

PMID- 8154431
TI  - Diagnosis of cardiac tamponade after cardiac surgery: relative value of clinical,
      echocardiographic, and hemodynamic signs.
AB  - Early detection and treatment of cardiac tamponade is crucial in management of
      patients after cardiac surgery. Because of the atypical features of this
      condition and paucity of data on relative frequency of different signs, we
      evaluated the sensitivity of various clinical, echocardiographic, and hemodynamic
      signs. We retrospectively evaluated the relative frequency of clinical,
      echocardiographic, and hemodynamic signs in 29 patients with cardiac tamponade
      after cardiac surgery. In our study 66% had a localized, posterior pericardial
      effusion, and the other 34% had circumferential pericardial effusion. In the
      whole group 24% of patients had hypotension, and pulsus paradoxus was noted in
      48%, right atrial collapse in 34%, right ventricular diastolic collapse in 27%,
      left ventricular diastolic collapse in 65%, and left atrial collapse in 13%.
      Elevation with equalization of pressures was noted in 81% patients. In the
      patient group with circumferential pericardial effusion and cardiac tamponade 40%
      patients were hypotensive and 50% patients had pulsus paradoxus. RA collapse was
      present in 70%, RV diastolic collapse in 70%, and LV diastolic collapse in 20%.
      Elevated diastolic pressures with equalization of these pressures was present in
      71%. In the group with regional pericardial effusion and cardiac tamponade
      hypotension was present in 16% and pulsus paradoxus in 47%. RA collapse was
      present in 16%, RV diastolic collapse in 5%, LV diastolic collapse in 89%, and LA
      collapse in 21% of the patients with regional tamponade. Elevated diastolic
      pressures with equalization of these pressures was noted in 86% of the patients.
      Our observations indicate that among patients who have undergone cardiac surgery
      the presentation of cardiac tamponade is usually atypical.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8154432
TI  - Epidemiology of congenital heart disease in the United States.
AB  - Data from the National Center for Health Statistics were examined to aid in
      assessing the burden of congenital heart disease in the United States. In 1979
      through 1988 combined, 46,450 deaths were attributed to CHD, 26,319 occurring in
      the first year of life. Another 14,283 deaths were attributed to other congenital
      anomalies of the circulatory system. In 1988 through 1990 combined, there were >
      300,000 hospital discharges with any diagnosis of CHD, with 2.7 million days of
      care provided. For infants aged < 1 year, the rate was 13.7 per 1000 live births
      per year. Another 242,049 discharges had any diagnosis of other congenital
      circulatory anomalies. In 1983 through 1985, > 700,000 persons reported a history
      of CHD. In 1989, heart malformations were reported on the birth certificate of
      4621 live births in 45 states and the District of Columbia. In 1988 through 1990
      there were an estimated 37,445 repairs of atrial and ventricular septa. In
      addition, 45,635 cardiac catheterizations were performed in patients aged < 5.
      Average annual percentage declines in infant mortality rates for the period 1979
      through 1988 were consistent with an effect of improvements in surgical technique
      and intensive care. The average annual infant mortality rate for hypoplastic left
      heart syndrome increased 1.3%, and rates for five causes amenable to treatment
      such as transposition of great vessels declined. Infant mortality rates in
      nonmetropolitan areas were higher than in metropolitan areas, suggesting that
      limited access to care might be associated with mortality.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8154433
TI  - Management of myocardial stunning associated with electroconvulsive therapy
      guided by hyperventilation echocardiography.

PMID- 8154434
TI  - Late presentation of left ventricular pseudoaneurysm and ventricular septal
      defect after surgery for penetrating cardiac injury.

PMID- 8154435
TI  - Avoiding a catastrophe: use of transesophageal echocardiography in diagnosing
      Salmonella aortitis.

PMID- 8154436
TI  - Transesophageal echocardiographically guided percutaneous biopsy of a right
      atrial cardiac mass.

PMID- 8154437
TI  - Idiopathic chylopericardium with bilateral pulmonary reflux of chyle.

PMID- 8154438
TI  - Subcostal two-dimensional echocardiographic identification of right superior vena
      cava connecting to left atrium.

PMID- 8154439
TI  - Transcatheter closure of a patent ductus arteriosus with an adjustable buttoned
      device in an adult patient.

PMID- 8154440
TI  - Closure of residual patent ductus arteriosus with occluding spring coil after
      implant of a Rashkind occluder.

PMID- 8154441
TI  - Direct current induction of atrial fibrillation.

PMID- 8154442
TI  - Sudden death after a stress test in a patient with a large pericardial cyst.

PMID- 8154443
TI  - Atrial flutter-fibrillation resulting from left atrial compression by an
      intrapericardial lipoma.

PMID- 8154444
TI  - Regional adrenergic denervation in ventricular fibrillation without apparent
      heart disease.

PMID- 8154445
TI  - Magnetic resonance angiography of congenital pulmonary vein anomalies.

PMID- 8154446
TI  - Fluctuations of interventricular shunting in a fetus with an isolated ventricular
      septal defect.

PMID- 8154447
TI  - Recalcitrant endocarditis successfully treated by heart transplantation.

PMID- 8154448
TI  - Atrial fibrillation, stroke, and antithrombotic treatment.

PMID- 8154449
TI  - Outbreak of Hantavirus pulmonary syndrome in the southwestern United States.
      Response of pathologists and other laboratorians.
AB  - During late spring and early summer of 1993, national and international media
      called worldwide attention to a cluster of deaths in the southwestern United
      States. These patients succumbed to a rapidly progressive severe respiratory
      distress syndrome. After notification of state and national health agencies in
      mid-May, a major effort was launched to determine the cause of this often fatal
      respiratory distress syndrome, to advise the public on safety measures, and to
      determine the method of spread of this "mystery illness." Within weeks of
      recognition of the early cases, the Centers for Disease Control and Prevention
      announced the probable agent, a Hantavirus. This report details the response of
      pathologists, medical technologists, and other laboratory scientists to this new
      viral epidemic, with emphasis on activities that occurred within New Mexico.

PMID- 8154450
TI  - Practical considerations in the laboratory diagnosis of bacterial enteric
      infections.
AB  - Diarrheal diseases caused by bacterial pathogens are important causes of
      morbidity in the United States, and considerable laboratory resources are spent
      to detect these enteric pathogens. This article reviews recent developments in
      the detection and identification of Campylobacter spp, enterohemorrhagic
      Escherichia coli, and Clostridium difficile, and outlines cost-effective
      strategies for use of stool cultures.

PMID- 8154451
TI  - The molecular approach to microbial diagnosis.
AB  - Nucleic acid technology is reshaping the laboratory approach to infectious
      diseases. The intrinsic advantages of the molecular diagnostic approach, coupled
      with rapid technical progress in this field, ensure its expanding role in
      clinical microbiology and virology. Interpretation of molecular tests requires a
      thorough understanding of their theoretical foundations, and laboratory
      professionals should renew their commitment to education in this area.

PMID- 8154452
TI  - Rapid diagnostic tests in microbiology in the 1990s.
AB  - The selection and management of all diagnostic tools should be guided in the
      1990s by carefully informed decisions. Concerns of test sensitivity and
      specificity must be balanced against cost. Although clinical judgment alone is
      often prompt and cost-effective, the risk of inaccuracy and serious consequences
      may be too great to forgo rapid diagnostic assays. The clinical effect and the
      imperatives in health care of the 1990s will guide the intelligent management and
      use of advancing rapid assay technology.

PMID- 8154453
TI  - A short history of Hodgkin's disease and Burkitt's lymphoma.
AB  - Although there are convincing descriptions of primary lymph node tumors dating
      from 1666, research into lymphoreticular disease began in 1832 when Thomas
      Hodgkin gave clinical descriptions and gross post mortem findings for seven
      cases. Later Reed and Sternberg concluded that Hodgkin's disease was indeed a
      different lesion with particular microscopical features. In the late 1950s,
      Burkitt described a tumor he observed in Uganda that affected the jaw. Originally
      it was called "round cell sarcoma." In 1961 Burkitt and O'Connor described the
      features of the clinical syndrome known today as Burkitt's lymphoma. Soon
      afterward, Wright established that this lymphoma was distinguished from other
      forms of lymphomas based on histopathologic features.

PMID- 8154454
TI  - The role of the microbiology laboratory in diagnosing mycobacterial diseases.
AB  - Recent surveys show that many mycobacteriology laboratories continue to use less
      than-optimal culture and susceptibility methods. This review summarizes available
      methods to diagnose. Mycobacterium tuberculosis. Although the local epidemiologic
      characteristics of M tuberculosis will partially determine what diagnostic
      measures are used, all laboratories should use a broth culture method in addition
      to a solid medium when culturing for M tuberculosis. Laboratories serving
      communities where drug resistance is common should use the BACTEC system for
      susceptibility testing or send isolates to a laboratory that uses it.
      Conventional testing in this setting must be aggressively discouraged. Rapid
      genetic amplification methods to detect mycobacteria in clinical specimens can
      greatly reduce the time needed to diagnose tuberculosis, especially if these
      methods can reliably detect M tuberculosis in smear-negative specimens. Many
      other diagnostic methods are being developed and clinicians and laboratories must
      regularly reassess whether a new method would be beneficial to their patients and
      the public.

PMID- 8154455
TI  - Comment on Class II elastics.

PMID- 8154456
TI  - Response to the Roth appliance treatment reply.

PMID- 8154457
TI  - Mucogingival orthodontic and periodontal problems.
AB  - The absence of keratinized gingiva alone is not an indication for a periodontal
      surgical procedure. However, if recession increases during orthodontic treatment,
      then a gingival graft may be indicated. Orthodontic therapy and removal of a
      mandibular incisor where excessive gingival recession is present may be the
      indicated treatment.

PMID- 8154458
TI  - Cephalometric assessment of sagittal relationship between maxilla and mandible.
AB  - This investigation was undertaken to evaluate if palatal plane could be used as a
      skeletal plane of reference in lateral cephalometric radiographs to evaluate
      sagittal maxillomandibular relationship. Various cephalometric landmarks in the
      maxilla and the mandible were projected to the palatal plane, and the linear
      distances between them were measured. In this three-part study, the first part
      evaluated changes in the inclination of palatal plane and in the linear distances
      from the age of 6 to 24 years in longitudinal records of 86 patients (46 male, 40
      female). The second part established acceptable adult norms by evaluating 111
      white dental students (89 men, 22 women) with Class I molar relationships, no
      history of orthodontic treatment, and good facial balance. The third part
      evaluated the proposed measures in pretreatment radiographs of 445 patients (171
      men, 274 women) with a variety of malocclusions to compare the results of various
      diagnostic criteria for assessment of sagittal jaw relationships. The first part
      indicated the inclination of the palatal plane was stable throughout the growth
      period studied. The distance between projections from points A and B on the
      palatal plane (App-Bpp) was found to be the best indicator of sagittal jaw
      relationship. This was the least variable of the four measures considered in part
      two of the study. When compared with the angle ANB, the Wits appraisal and
      measurement of landmarks to a perpendicular from nasion in 50 patients, it was a
      more reliable diagnostic criterion than the other measures. Among the patients
      whose malocclusions were incorrectly diagnosed. Wits appraisal was consistently
      biased in the Class III direction. The methods using the ANB angle and the nasion
      perpendicular plane did not indicate any definitive trend.

PMID- 8154459
TI  - A radiographic study of posterior apical root resorption in orthodontic patients.
AB  - The purpose of this study was to determine the extent of apical root resorption,
      after fixed appliance therapy, in the posterior part of the dentition, and to
      evaluate if predisposing factors can be pointed out retrospectively. Tooth length
      in the posterior part of the dentition was measured on pretreatment and
      posttreatment orthopantomograms of 153 patients who were treated with standard
      edgewise appliances. Pretreatment and posttreatment tooth lengths were
      determined, and an attempt was made to explain the differences by sex, age, stage
      of root formation at onset of orthodontic treatment, extraction versus
      nonextraction therapy and treatment duration. Patients were divided into two
      groups according to their root formation. Group A consisted of patients with
      incompleted root formation at onset of orthodontic treatment except for the first
      molars. Group B consisted of patients where root formation was completed with the
      exception of second and third molars. Posttreatment tooth lengths of groups A and
      B were compared with pretreatment tooth lengths of group B with a paired t test,
      and correlations with the variables were calculated with multiple regression
      analysis only in group B. Posttreatment group A showed no significant differences
      with the mean root lengths of pretreatment group B. Differences between the mean
      pretreatment and posttreatment root lengths in group B were significant.
      Posterior teeth showed root shortening during active orthodontic treatment
      independent of sex, age, extraction versus nonextraction therapy, and duration of
      active treatment. Teeth with incompleted root formation at onset of orthodontic
      treatment showed root lengthening during active treatment, yet did not reach
      their "normal" tooth length.

PMID- 8154460
TI  - Apical root resorption in orthodontically treated subjects: analysis of edgewise
      and light wire mechanics.
AB  - Of the several modes of tooth movement, pressure from intrusive forces seems the
      most likely to cause external apical root resorption (EARR). This has been
      demonstrated for incisors in human beings and molars in laboratory animals. The
      present study examined full-banded adolescent patients and scored the degrees of
      in-treatment root resorption throughout the dentition. Just Class I cases with
      four first premolar extractions were used. Equal samples of conventional Begg and
      Tweed treated cases were examined with 1:1 sex ratios (total n = 83). No
      difference between the Begg and Tweed techniques and no sex difference was found
      in any of the 30 univariate tests, even though power analysis indicated a strong
      likelihood of finding a difference if one existed. By using multiple linear
      regression, significant decreases in length (EARR) were found for those roots
      systematically intruded in this Class I malocclusion, notably the mesial root of
      the maxillary first molar and the distal root of the mandibular first molar. Even
      though some of the present cases had been in "active" treatment up to 6 years, we
      found no significant association between duration of treatment and degree or
      amount of EARR.

PMID- 8154461
TI  - Some "sealants" seal--a scanning electron microscopy (SEM) investigation.
AB  - White spot lesions of enamel around orthodontic brackets as a result of
      demineralization have been well documented in the orthodontic literature. Various
      methods of treatment have been attempted to reduce or eliminate this danger. The
      purpose of this study was to evaluate, by means of scanning electron microscopy,
      the polymerization of the sealant layer around orthodontic brackets with direct
      and indirect methods of bonding. Twenty-four sound human lateral maxillary
      incisor teeth were collected, cleaned, divided equally into four groups A through
      D, and stored in 70% ethyl alcohol. Their buccal surfaces were pumiced, etched
      with 37% phosphoric acid for 1 minute, and washed under running water for 30
      seconds. Metal brackets were bonded with the chemically cured BIS-GMA resin,
      Ortho Concise, as follows: group A, indirectly bonded with coping; group B,
      indirectly bonded without coping; and group C, directly bonded; light activated
      Transbond was used in group D, directly bonded brackets. After washing in alcohol
      for 20 seconds, all teeth were dried, and sectioned longitudinally, through the
      middle of the bracket. All were subjected to 5% hydrochloric acid for 30 seconds
      and then washed under running water for 30 seconds. After drying and sputter
      coating, the teeth were viewed under scanning electron microscopy. Groups A and D
      showed a sealant layer surrounding the brackets and covering the buccal enamel.
      Groups B and C showed total absence of a cured sealant layer around the brackets
      or surrounding enamel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154462
TI  - Prostaglandin E (PGE) and interleukin-1 beta (IL-1 beta) levels in gingival
      crevicular fluid during human orthodontic tooth movement.
AB  - The purpose of this study was to examine gingival crevicular fluid (GCF) levels
      of two potent bone resorbing mediators, prostaglandin E (PGE) and interleukin-1
      beta (IL-1 beta), during human orthodontic tooth movement. The study included 10
      patients, each having one treatment tooth undergoing orthodontic movement and a
      contralateral control tooth. The GCF was sampled at control sites and treatment
      (compression) sites before activation and a 1, 24, 48, and 168 hours. Prevention
      of plaque-induced inflammation allowed this study to focus on the dynamics of
      mechanically stimulated PGE and IL-1 beta GCF levels. The PGE and IL-1 beta
      levels were determined with radioimmunoassay. At 1 and 24 hours, mean GCF IL-1
      beta levels were significantly elevated at treatment teeth (8.9 +/- 2.0 and 19.2
      +/- 6.0 pg, respectively) compared with control teeth (2.0 +/- 1.1 pg, p =
      0.0049, and 2.9 +/- 1.0 pg, p = 0.0209, respectively). The GCF levels of PGE for
      the treatment teeth were significantly higher at 24 and 48 hours (108.9 +/- 11.9
      and 97.9 +/- 7.3 pg) than the control teeth (61.8 +/- 7.2 pg, p = 0.0071, and
      70.8 +/- 7.4 pg, p = 0.0021, respectively). The GCF levels of PGE and IL-1 beta
      remained at baseline levels throughout the study for the control teeth, whereas
      significant elevations from baseline in GCF IL-1 beta (24 hours) and PGE levels
      (24 and 48 hours) were observed over time in the treatment teeth (p < or =
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154463
TI  - Long-term control of the stability of skeletal structures in Class II
      dentoskeletal deformities after surgical-orthodontic therapy.
AB  - This study analyzes long-term findings in a group of 10 patients with Class II
      dentoskeletal malrelationship and who have undergone orthognathic surgical
      procedures. Changes in cephalometric values relative to the bony structures of
      the upper jaw and of the mandible are discussed in detail. Patients were
      reexamined on average, 5.8 years after surgery to show possible modification of
      the skeletal regions in patients who underwent surgical-orthodontic treatment for
      malformation of the facial continuum. For each case we made a cephalometric
      analysis of the lateral cephalograms, as well as the superimposition of tracings
      relative to the various stages of treatment: at the end of preoperative
      orthodontic treatment, after surgery, and at the long-term control. Cephalometric
      values for all patients who took part in this long-term control were recorded and
      a structural assessment was made.

PMID- 8154464
TI  - The quantification of soft tissue cervicomental changes after mandibular
      advancement surgery.
AB  - Surgical mandibular advancement results in many soft tissue changes. The purpose
      of this study was to quantify the changes seen in the cervicomental angle and the
      lip-chin-throat angles in response to mandibular advancement, as well as hyoid
      bone positional changes. As a result of statistical analysis of hyoid bone and
      soft tissue linear and angular changes, prediction models are presented as to the
      soft tissue response to mandibular advancement in the cervicomental region.

PMID- 8154465
TI  - An evaluation of the torsional moments developed in orthodontic applications. An
      in vitro study.
AB  - The amount of play between brackets and wire and the magnitude of the torsional
      moments developed have been investigated for six different rectangular wires. The
      study simulated the situation occurring when torque is applied to an individual
      central incisor. The observed play between wire and bracket ranged from about 5
      degrees between an 0.018 x 0.025 inch in an 0.018-inch bracket slot, to
      approximately 20 degrees for a 0.016 x 0.022 inch in an 0.018-inch bracket slot.
      The observed rate of change after the play had been eliminated, varied from 0.24
      degrees/Nmm to 0.37 degrees/Nmm for the steel wires, whereas 0.017 x 0.025-inch
      nitinol had a rate of change of approximately 1.07 degrees/Nmm. The use of
      ligatures demonstrated that a torque effect could be observed even though the
      play had not been completely eliminated.

PMID- 8154466
TI  - Reaction of the pterygomaxillary fissure and the condylar cartilage to
      intermaxillary Class III magnetic mechanics.
AB  - The skeletal reaction to Class III intermaxillary magnetic mechanics was
      previously found to affect two target areas, the pterygomaxillary fissure (PMF)
      and the condylar cartilage. The objectives of this study were to analyze,
      radiographically and histologically, the response of these tissues to Class III
      intermaxillary functional orthopedic magnetic appliance (FOMA III), and to
      postulate possible models of their dichotomous biomechanism. Nine Macaca
      fascicularis monkeys received periodic administration of vital bone procion dye
      and were treated for 4 months with FOMA III (6 subjects) and sham appliance (3
      subjects). The PMF (the target area of the midfacial complex) demonstrated a
      decreased skeletal reaction in inferosuperior and lateromedial directions.
      Cephalometrically, the lowermost PMF point was displaced inferiorly 1.98 +/- 1.74
      mm and 0.42 +/- 0.38 mm and anteriorly 1.42 +/- 0.96 mm and 0.58 +/- 0.38 mm in
      the treated and control groups, respectively. The displacement of the uppermost
      PMF point, compared with the lowermost point, was three to five times lower.
      Histologically, two modes of response were found; first, a sutural response
      (disarticulation and osteogenesis) of the palatomaxillary and pterygopalatine
      sutures, which was distinctive of the lateral PMF aspect, and second, a
      dentosutural response, which was characteristic of the medial PMF aspect (bony
      microfractures between the third molar germ and the maxillary tuberosity in
      conjunction with mild sutural response). In the mandible, a discrepancy was found
      between the histologic and the cephalometric findings. Radiographically,
      mandibular length was unaffected after 4 months of treatment, and the distance
      condylion-pogonion was equally increased in the treated (0.75 +/- 0.78 mm) and
      the control animals (0.77 +/- 0.32 mm). Histologically, however, the condylar
      cartilage demonstrated increased osteoclastic activity at the zone of
      endochondral ossification and a decreased apposition rate at the adjacent bony
      trabeculae. Conceivably, the two target areas (PMF sutures versus condylar
      cartilage) demonstrate two diverse time-related responses that are either
      unrelated or interrelated to each other. An unrelated tissue response suggests
      that tissue stimulation (sutural) is always superior to tissue suppression
      (condylar). Another possible unrelated tissue reaction implies diverse response
      velocity (high sutural, low condylar). An interrelated mechanism suggests that an
      applied force will dissipate initially at the less resistant target area
      (sutures), and will subsequently affect the more resistant target area (condyle)
      once the sutural resistance exceeds a certain threshold. The fact that no
      pathologic change was found in the condylar cartilage encourages a long-term use
      of the FOMA III appliance, initiating treatment at an early skeletal age.

PMID- 8154467
TI  - Faustin Neff Weber.

PMID- 8154468
TI  - The perfect business program.

PMID- 8154469
TI  - Dietary glutathione intake and the risk of oral and pharyngeal cancer.
AB  - Glutathione, a tripeptide found in a variety of foods, may function as an
      anticarcinogen by acting as an antioxidant and by binding with cellular mutagens.
      The association between dietary glutathione intake and risk of oral and
      pharyngeal cancer was investigated using data from 1,830 white participants (855
      cases and 975 controls) in a population-based case-control study conducted in New
      Jersey; metropolitan Atlanta, Georgia; Los Angeles County, California; and Santa
      Clara and San Mateo counties, south of San Francisco-Oakland, California, during
      1984-1985. The estimated relative risk of cancer among people with the highest
      quartile of glutathione intake from all sources was 0.5 (95% confidence interval
      0.3-0.7). When analyzed by dietary source, however, glutathione intakes derived
      from all vegetables and from meat were not related to risk of cancer. Only
      glutathione derived from fruit and from vegetables commonly consumed raw was
      associated with reduced oral cancer risk. Relative to the lowest level of
      combined intake of fruit and of fruit-derived glutathione, risk of cancer
      decreased slightly with increasing intake of fruit glutathione. This analysis was
      limited, however, by the small numbers of subjects with extreme combinations of
      intakes. Further studies are needed to distinguish the potential effect of
      glutathione from that of fruit and raw vegetables per se or from the influence of
      other constituents in these foods.

PMID- 8154470
TI  - Nutritional factors and gastric cancer in Spain.
AB  - A case-control study on diet and gastric cancer, carried out in selected areas of
      four regions of Spain (Aragon, Castile, Catalonia, and Galicia) in 1988 and 1989,
      included 354 cases of histologically confirmed gastric adenocarcinoma and 354
      controls matched by age, sex, and area of residence. Cases and controls were
      selected from 15 hospitals, representing most of the hospital facilities in the
      study areas. Usual diet was estimated by means of a dietary history questionnaire
      administered by interview. An increased risk of gastric cancer was observed for
      high consumption of exogenous nitrosamines (odds ratio = 2.1 for the highest
      quartile of consumption versus the lowest; p for linear trend = 0.007), nitrites,
      fat, and cholesterol. However, in a multivariate regression model, the effect of
      fat and cholesterol disappeared. An inverse association with the risk for gastric
      cancer was seen for high intake of fiber, vitamin C, folate, carotene, and
      nitrates. High consumption of vitamin C seemed to neutralize the increased risk
      related to simultaneous consumption of nitrosamines. For histologic type, the
      authors found no meaningful differences in the effect of most of the nutrients
      between intestinal and diffuse cancers. Their findings are consistent with
      previously reported results about the protective effect of fruit and vegetables
      and the increased risk associated with foods that are important sources of
      nitrites and preformed nitrosamines.

PMID- 8154471
TI  - Greater case-fatality after myocardial infarction among Mexican Americans and
      women than among non-Hispanic whites and men. The Corpus Christi Heart Project.
AB  - Age-adjusted 28-day case-fatality rates were higher among Mexican Americans than
      among non-Hispanic whites and higher among women than among men hospitalized for
      definite or possible myocardial infarction in Corpus Christi, Nueces County,
      Texas, from May 1, 1988, through April 30, 1990. The authors therefore examined
      whether these higher case-fatality rates were associated with greater prevalence
      of previously diagnosed coronary heart disease or diabetes; with greater age,
      frequency of definite myocardial infarction, or congestive heart failure; with
      higher values of indicators of severity of infarction, including peak creatine
      phosphokinase levels and scales prognostic of early mortality after myocardial
      infarction; and with differences in receipt of in-hospital therapy. The overall
      28-day case-fatality rate among 1,228 patients hospitalized for myocardial
      infarction during a 24-month period was 7.3%. After adjustment for age; diabetes;
      myocardial infarction class (definite vs. possible); congestive heart failure;
      the Norris and Peel severity indices; peak total creatine phosphokinase; and
      receipt of thrombolytic therapy, aspirin, calcium channel blockers, beta
      blockers, anticoagulants, angioplasty, and bypass surgery, the risk of 28-day
      case-fatality for Mexican Americans in relation to non-Hispanic whites was 1.49
      (95% confidence interval 0.92-2.40). The corresponding risk for women in relation
      to men was 1.80 (95% confidence interval 1.12-2.89). These findings should alert
      clinicians to the high-risk status of these groups of patients.

PMID- 8154472
TI  - Ingested inorganic arsenic and prevalence of diabetes mellitus.
AB  - To examine the association between ingested inorganic arsenic and prevalence of
      diabetes mellitus, in 1988, the authors studied 891 adults residing in villages
      in southern Taiwan where arseniasis is hyperendemic. The status of diabetes
      mellitus was determined by an oral glucose tolerance test and a history of
      diabetes regularly treated with sulfonylurea or insulin. The cumulative arsenic
      exposure in parts per million-years was calculated from the detailed history of
      residential addresses and duration of drinking artesian well water obtained
      through standardized interviews based on a structured questionnaire and the
      arsenic concentration in well water. The body mass index was derived from body
      height and weight measured according to a standard protocol, while the physical
      activity at work was also obtained by questionnaire interviews. Residents in
      villages where the chronic arseniasis was hyperendemic had a twofold increase in
      age- and sex-adjusted prevalence of diabetes mellitus compared with residents in
      Taipei City and the Taiwan area. There was a dose-response relation between
      cumulative arsenic exposure and prevalence of diabetes mellitus. The relation
      remained significant after adjustment for age, sex, body mass index, and activity
      level at work by a multiple logistic regression analysis giving a multivariate
      adjusted odds ratio of 6.61 and 10.05, respectively, for those who had a
      cumulative arsenic exposure of 0.1-15.0 and greater than 15.0 ppm-year compared
      with those who were unexposed. These results suggest the chronic arsenic exposure
      may induce diabetes mellitus in humans.

PMID- 8154473
TI  - Case-control study of risk factors for hip fractures in the elderly.
AB  - The objective of this population-based case-control study was to identify risk
      factors for hip fracture among elderly women and men, particularly factors during
      young and middle adult life. The study base comprised people aged 65 years and
      over living in a defined region in Sydney, Australia, during 1990-1991. Cases
      were recruited from 12 hospitals, and controls were selected using an area
      probability sampling method, with additional sampling from nursing homes. There
      were 416 subjects (209 cases and 207 controls); proxy respondents were needed for
      27 percent of the subjects. Smoking, underweight in old age, overweight at age 20
      years, and weight loss were associated with an increased risk of hip fracture.
      Consumption of dairy products, particularly at age 20 years, was associated with
      an increased risk of hip fracture in old age. Multivariate-adjusted odds ratios
      for quintiles of dairy product consumption at age 20 years were 1.0 (lowest
      quintile), 0.8, 1.8, 3.4, 2.9 (highest quintile). Caffeine and alcohol intake
      were not associated with hip fracture risk. Some of the results of this study
      were unanticipated and may be due to chance or bias. If confirmed by other
      studies, these results would challenge some current approaches to hip fracture
      prevention.

PMID- 8154474
TI  - Longitudinal study of Borrelia burgdorferi infection in New Jersey outdoor
      workers, 1988-1991.
AB  - From 1988 to 1991, annual questionnaires and serosurveys were performed in a
      cohort of outdoor workers in New Jersey at high risk for Lyme disease to 1)
      evaluate temporal trends in seroprevalence and seroconversion of antibody to
      Borrelia burgdorferi; 2) identify risk factors for B. burgdorferi seroconversion
      during these years; and 3) examine associations between such seroconversion in
      1989-1990 and anti-tick saliva antibody (ATSA, a biologic marker of tick
      exposure) seropositivity in 1990. A total of 1,519 workers participated in at
      least 1 year of the study. Lyme disease seroprevalence and seroconversion
      increased from 1988 to 1990 and then decreased in 1991. Years at residence, rural
      residence, and a history of medical problems were observed to be risk factors for
      seroconversion from 1988 to 1991. An interaction between pet ownership and rural
      residence was observed in that rural residents were only at an elevated risk if
      they owned pets. B. burgdorferi seroconversion from 1989 to 1990 was associated
      with ATSA seropositivity in 1990; in subjects reporting low tick exposure, the
      odds ratio was 8.2 (95% confidence interval 1.5-44.7). Associations between ATSA
      and B. burgdorferi serologic status suggested that educational programs may have
      contributed to the decline in Lyme seroprevalence and seroconversion in 1991.

PMID- 8154475
TI  - Seroprevalence of Helicobacter pylori infections in a cohort of US Army recruits.
AB  - To study the prevalence and risk factors of Helicobacter pylori infection in
      healthy young adults, sera were collected from a nationwide sample of 404 females
      and 534 males (mean age, 20.2; range, 17-26 years) at induction into the US Army
      at Fort Jackson, South Carolina, during the fall of 1990. An enzyme-linked
      immunosorbent assay (PYLORI STAT, BioWhittaker, Inc., Walkersville, MD) was used
      to detect H. pylori-specific immunoglobulin G antibodies. Demographic data were
      obtained from a personnel database and by linking US census information to the
      subject's home address. The observed crude seropositivity rate was 26.3% (95%
      confidence interval 23.2-28.9). The direct sex-, race-, and geographic region
      adjusted seropositivity rate was 20.8% (95% confidence interval 17.9-23.7).
      Seropositivity rates for blacks, Hispanics, and whites were 44%, 38%, and 14%,
      respectively, (chi 2, p < 0.001), and rates increased progressively from 24% in
      the age group 17-18 years to 43% in the age group 24-26 years (chi 2 for trend, p
      < 0.001). The age trends remained strong after controlling for race Median income
      was also an important predictive variable for seropositivity (chi 2, p < 0.0001).
      Sex, the percent urbanization, and population density of the home county were not
      significant predictors of seropositivity when age and race-ethnic group were
      controlled in a statistical model. The sharp increase in seroprevalence in this
      narrow age range suggests that the incidence rates are higher in young adults
      than previously reported.

PMID- 8154476
TI  - Risk factors for transmission of Mycobacterium tuberculosis in a primary school
      outbreak: lack of racial difference in susceptibility to infection.
AB  - Recent data have suggested that there are racial differences in the
      susceptibility to infection by Mycobacterium tuberculosis. An opportunity to test
      this suggestion was afforded by an outbreak of tuberculosis in a racially mixed
      elementary school in St. Louis County, Missouri. A physical education teacher was
      discovered to have cavitary pulmonary tuberculosis. Of 343 students in the
      school, 176 (51 percent) were found to be tuberculin skin test positive (> or = 5
      mm induration by Mantoux method); 32 children had abnormal chest radiographs.
      More frequent contact with the physical education teacher was associated with
      infection (p < 0.001). Black children were no more likely to be infected than
      were white children (relative risk (RR) = 0.98, 95% confidence interval (CI) 0.78
      1.22). However, black children who were tuberculin positive had larger skin
      reactions than did white children (mean, 18.9 vs. 16.6 mm, p < 0.001) and were
      more likely to have abnormal chest radiographs (RR = 2.76, 95% CI 1.44-5.27).
      Among tuberculin-positive children, low body mass index (less than 10th
      percentile) was associated with active disease (RR = 2.90, 95% CI 1.45-5.80). The
      analysis of race was unchanged after controlling for sex, body build, and level
      of contact with the physical education teacher. Widespread tuberculous infection
      resulted from contact with a highly infectious staff person. Thin body build was
      a risk factor for active disease. Black children were no more susceptible to
      infection than were white children, although they more commonly developed
      radiographic evidence of active disease.

PMID- 8154477
TI  - Invited commentary: relative susceptibility of black Americans to tuberculosis.

PMID- 8154478
TI  - How to find a wombmate: validation of an algorithm to identify twin pairs in
      Linked Birth/Infant Death Files.
AB  - Linked Birth/Infant Death Files available from the National Center for Health
      Statistics identify an infant as a twin, but do not identify twin pairs. An
      algorithm based on maternal, paternal, and infant characteristics has been used
      to identify twin pairs, but the validity of this algorithm has never been tested.
      The Missouri linked birth/infant death file from 1980 to 1990 identifies twin
      pairs by a sequence number. The authors tested the rate and accuracy with which
      the algorithm identified true pairs in the Missouri file and whether estimates of
      risk and possible risk factors calculated from pairs of twins identified by the
      algorithm agreed with these characteristics as calculated from known twin pairs.
      The algorithm identified 96% (8,273 of 8,620) of true pairs and one false pair.
      Despite incomplete pair identification, and even identification of a false pair,
      estimates from the subset identified by the algorithm generally agreed well with
      characteristics measured from all twin pairs. Nonetheless, incorporation of a
      multiple birth sequence number into Linked Birth/Infant Death Files would enhance
      their utility.

PMID- 8154479
TI  - Re: "Increased risk of breast cancer with alcohol consumption in postmenopausal
      women".

PMID- 8154480
TI  - Re: "Child care increases the risk of clinic visits for acute diarrhea and
      diarrhea due to rotavirus".

PMID- 8154481
TI  - Re: "Blood lead as a cardiovascular risk factor".

PMID- 8154482
TI  - Re: "Alcohol and mortality in Busselton, Western Australia".

PMID- 8154483
TI  - Extrarenal complications of the nephrotic syndrome.
AB  - The systemic complications of nephrotic syndrome are responsible for much of the
      morbidity and mortality seen with this condition. This review discusses the
      causes for the hypoalbuminemia and the associated metabolic abnormalities of the
      nephrotic syndrome. No unifying hypothesis exists for the induction, maintenance,
      and resolution of nephrotic edema. In view of the wide spectrum of renal diseases
      leading to the nephrotic syndrome, more than a single mechanism may be
      responsible for the renal salt retention in these diverse conditions. Although
      hypoalbuminemia may be important, especially when plasma oncotic pressure is very
      low (serum albumin < 1.5 to 2.0 g/dL), primary impairment of salt and water
      excretion by the nephrotic kidney appears to be a major factor in pathogenesis of
      the edema. However, the decreased serum albumin and/or oncotic pressure seen with
      nephrotic syndrome is a major contributing factor to the development of the
      hyperlipidemia of nephrotic syndrome. Patients with unremitting nephrotic
      syndrome should be considered for combined dietary and lipid-lowering drug
      therapy. Urinary losses of binding proteins lead to the observed abnormalities in
      the endocrine system and in trace metals, and urinary losses of coagulation
      factors contribute to the hypercoagulable state. At present, selective renal
      venography is recommended when the suspicion of renal vein thrombosis is
      justified by clinical presentation. The impact on renal function caused by
      treating asymptomatic chronic renal vein thrombosis is undetermined, but
      anticoagulation for chronic renal vein thrombosis is associated with relatively
      few complications.

PMID- 8154484
TI  - Percutaneous native renal biopsy: comparison of a 1.2-mm spring-driven system
      with a traditional 2-mm hand-driven system.
AB  - Over the last few years spring-driven mechanical biopsy guns have been introduced
      for performing renal biopsies. There has been little research done comparing
      these guns with traditional hand-driven needles in performing biopsies of native
      kidneys. We wished to compare our experience with the two needle types. We
      studied retrospectively the results and complication rates of 155 native kidney
      biopsies. Sixty-nine were performed with hand-driven 14-gauge needles and eighty
      six with 18-gauge, spring-driven biopsy guns. Sufficient tissue for diagnosis was
      obtained in 96% of cases in the hand-driven group compared with 99% in the biopsy
      gun group (P = NS). Complications occurred in six cases in the hand-driven group
      compared with one case in the biopsy gun group (P = 0.02). As expected, the
      reported number of glomeruli per core in the 14-gauge cores was greater than in
      the 18-gauge cores (16.5 v 6.2, P < 0.01). This was partially offset by the
      greater number of passes made with the smaller needle. We conclude that similar
      results can be expected from both biopsy methods, with a possible slight decrease
      in complications using biopsy guns with smaller needle diameters.

PMID- 8154485
TI  - Patterns of fasting plasma amino acid levels in chronic renal insufficiency:
      results from the feasibility phase of the Modification of Diet in Renal Disease
      Study.
AB  - Fasting plasma amino acid levels were measured in 78 patients with chronic renal
      insufficiency (glomerular filtration rate [GFR], 8.0 to 56.0 mL/min), who had
      been enrolled in phase II of the Modification of Diet in Renal Disease study,
      prior to their beginning the experimental portion of the protocol. Alterations in
      many plasma amino acid levels were observed in the patients with the mildest
      degrees of renal insufficiency, and the number and severity of abnormalities
      tended to be greater in the patients with more severe renal failure. In patients
      with GFRs greater than 24.5 mL/min, 15 to 24.5 mL/min, and less than 15 mL/min,
      statistically significant abnormalities were observed in the concentrations or
      ratios of 9, 14, and 18 amino acids, respectively. The following correlations of
      amino acid levels or ratios with GFR were observed (all P < 0.001): citrulline, r
      = -0.41; citrulline to arginine ratio, r = -0.42; glycine to serine ratio, r = 
      0.37; N-tau methylhistidine, r = -0.65; and cystine, r = -0.37. Other weaker
      correlations observed were valine, r = 0.26 (P < 0.025); valine to glycine ratio,
      r = 0.32 (P = 0.004); and sum of isoleucine, leucine, and valine, r = 0.21 (P =
      0.061). N-tau methylhistidine and the essential to nonessential amino acid ratio
      became altered with declining GFR in a nonlinear fashion. Thus, many of the
      characteristic alterations in the plasma amino acid profile that are observed in
      chronic end-stage renal disease are already present in mild renal insufficiency.
      Progressive loss of renal function generally results in increasing abnormalities;
      these changes in plasma amino acid concentrations with reduction in GFR were
      usually linear.

PMID- 8154486
TI  - Serum lipid changes associated with modified protein diets: results from the
      feasibility phase of the Modification of Diet in Renal Disease Study.
AB  - The use of low-protein diets for the management of progressive renal
      insufficiency may require increases in dietary fats to maintain caloric balance.
      This raises the concern that such diets might exacerbate the lipid problems
      already prevalent in chronic renal insufficiency. We present a study in which
      protein-restricted diets were followed by a group of patients with renal
      insufficiency without a compensatory increase in fat calories and without adverse
      effects on serum lipids. Ninety-six patients with renal insufficiency were
      enrolled in the feasibility phase of the Modification of Diet in Renal Disease
      Study and were assigned to dietary protein intakes of 1.3, 0.575, or 0.28 g/kg
      body weight/d. The last diet was supplemented with amino acids or their keto
      analogs. Of this group, 25 participants were excluded from the present study of
      lipids because of changes in their intake of medications with known effects on
      serum lipids, three were excluded because of proteinuria increasing by more than
      2 g/d, and seven were excluded because of incomplete measurements. For the
      remaining 61 participants, median serum total cholesterol at baseline was 215
      mg/dL. In 72% of participants it exceeded the age- and sex-adjusted median of the
      Lipid Research Clinics Prevalence Study. Glomerular filtration rates varied from
      8 to 56 mL/min/1.73 m2. The patients' serum lipid levels were stable by 6 months
      on assigned diets. Serum total and low-density lipoprotein cholesterol levels
      tended to decrease with reduced protein intake. The baseline to follow-up change
      in protein intake calculated from urinary urea measurements was significantly
      correlated with the change in serum total cholesterol (Spearman r = 0.31, P <
      0.05) and also with change in low-density lipoprotein cholesterol (r = 0.34, P <
      0.01). Surprisingly, correlations between change in serum cholesterol and intake
      of fats were small in magnitude and did not approach statistical significance.
      Protein intake did correlate, however, with intake of cholesterol. We conclude
      that the use of low-protein diets for patients with renal insufficiency did not
      adversely affect serum lipids.

PMID- 8154487
TI  - An analysis of the approach to management of childhood nephrotic syndrome by
      pediatric nephrologists.
AB  - The value of a renal biopsy for a child with frequently relapsing corticosteroid
      responsive or corticosteroid-dependent nephrotic syndrome is unresolved. This was
      the subject of two independent surveys done by North American pediatric
      nephrologists. In one study, 59% of the respondents indicated that they would
      nearly always perform a biopsy prior to starting cytotoxic therapy, while 23%
      would do so rarely. Less experienced pediatric nephrologists were more inclined
      to recommend a biopsy (P < 0.05). The indications for a renal biopsy were to
      provide prognostic information and to make decisions concerning further therapy.
      In the second survey, 33% of pediatric nephrologists said they would perform a
      renal biopsy in children with frequent relapses, while 91% would recommend a
      biopsy in children with corticosteroid resistance (P < 0.001). Once a biopsy was
      performed, therapy was based on the histopathologic findings regardless of the
      previous clinical response to corticosteroids. At this time, there is no standard
      approach to the evaluation and management of children with frequently relapsing,
      corticosteroid-dependent nephrotic syndrome. Some physicians rely on their
      clinical acumen, whereas others depend on the histopathologic findings.

PMID- 8154488
TI  - Chronic nephrotoxicity in psoriatic patients treated with low-dose cyclosporine.
AB  - Chronic nephrotoxicity is a major complication in high-dose cyclosporine
      treatment. We examined the glomerular filtration rate, renal plasma flow, and
      kidney biopsies of 15 psoriatic patients treated with low-dose cyclosporine (< or
      = 5 mg/kg/d) for 30 months (25 to 35 months) 1 month after drug withdrawal. The
      mean (95% confidence interval) age of the patients in the study was 44 years (38
      to 50 years). Their serum creatinine levels pretreatment and at the time of the
      study were 0.94 mg/dL (0.85 to 1.0 mg/dL) and 1.2 mg/dL (1.1 to 1.3 mg/dL). Seven
      patients had a decreased glomerular filtration rate and four of them also had a
      reduced renal plasma flow, below the 2.5 percentile of normal. Four patients had
      moderate tubulointerstitial scarring and arteriolopathy, while the remaining
      patients had mild structural abnormalities. The severity of acute nephrotoxicity
      during treatment and chronic structural injury were highly correlated (r = 0.81;
      P < 0.0003). Recurrent episodes of severe acute nephrotoxicity (defined as
      reversible increase of serum creatinine > 90% of baseline value) was a marker for
      moderate chronic nephrotoxicity. No correlation was found between chronic
      structural injury and patient age, sex, pretreatment creatinine level, blood
      pressure (pretreatment or during treatment), cyclosporine dose and treatment
      duration, and cyclosporine blood levels. In seven patients continued on
      cyclosporine for another 12 months (10 to 14 months), repeat studies showed no
      interval changes. Despite 40 months (30 to 51 months) of treatment, all but one
      of these seven patients (with previous hypertension and atherosclerotic vascular
      disease) had mild functional and structural abnormalities. None had any severe
      acute nephrotoxicity at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154489
TI  - Hepatitis B virus infection in chronic uremia: long-term follow-up of a two-step
      integrated protocol of vaccination.
AB  - Active immunization is crucial for eradicating hepatitis B virus infection from
      dialysis units. A prospective study was performed in 63 consecutive chronic
      uremic patients, which included the following: (1) the intramuscular (IM)
      administration of 40 micrograms of a DNA-recombinant vaccine (Engerix-B, Smith
      Kline & French Laboratories, Milan, Italy) to all chronic uremic patients at 0,
      1, 2, and 6 months; (2) the antibody titer determination at the seventh month
      (chronic uremic patients with a titer > 100 mIU/mL received an IM booster dose of
      40 micrograms at 18 months [group A], and those with a titer < 100 mIU/mL
      received a further IM dose of 40 micrograms at 12 months [group B]); and (3) the
      intradermal inoculation of 5 micrograms of vaccine every 2 weeks until the
      protective titer (> or = 10 mIU/mL) was achieved, and then monthly for 6 months,
      in chronic uremic patients who did not have a protective titer even after 19
      months (group C). Thus, 41, 17, and five chronic uremic patients were allocated
      to groups A, B, and C, respectively. All developed a protective titer: 79.4%,
      84.0%, and 87.5% after the fourth, fifth, and sixth IM dose at 7, 13, and 19
      months, respectively. Five chronic uremic patients (group C) achieved
      seroprotection after 3.8 +/- 0.5 (SEM) intradermal inoculations.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8154490
TI  - Molecular analysis of C3 allotypes in Chinese patients with immunoglobulin A
      nephropathy.
AB  - The third component of complement (C3) exists in two main allotypic forms, C3S
      and C3F. An increased frequency of the rarer C3F allele has been reported in
      several autoimmune conditions, including immunoglobulin A nephropathy (IgAN), in
      white patients. C3F is known to be rare in the Chinese population, but C3
      allotypes have not been studied in Chinese patients with IgAN. The molecular
      basis of the S/F polymorphism has been established recently: a single base change
      at the DNA level encodes a single amino acid substitution in the protein. A
      second polymorphism, closely linked to the first, is defined by the monoclonal
      antibody HAV 4-1, and also is due to a single base change. These polymorphisms
      therefore can be analyzed at the DNA level. We have used the amplification
      refractory mutation system, a modification of the polymerase chain reaction, to
      analyze these two C3 polymorphisms on genomic DNA from 133 Hong Kong Chinese
      individuals: 54 patients with IgAN and 79 controls. No C3F alleles were present
      in either group: all individuals were homozygous C3S. Twenty-six patients were
      also allotyped for the HAV 4-1 polymorphism; all 26 were homozygous HAV 4-1
      negative, as would be predicted from the close linkage of this allotype to C3S in
      other populations. These data indicate that C3F is not a susceptibility allele
      for IgAN in Hong Kong Chinese individuals, and confirm in a large DNA-based study
      the rarity of C3F in this population.

PMID- 8154491
TI  - An epidemiologic analysis of end-stage lupus nephritis.
AB  - We analyzed 566 patients (515 females and 51 males) with systemic lupus
      erythematosus who were treated in Okinawa, Japan, from 1972 to 1991 and followed
      until April 1993. One hundred four patients (95 females and 9 males) died, and 51
      were considered to have end-stage lupus nephritis. The annual incidence and
      prevalence, per million population in each sex, were increased from 16.0 and 66.0
      in 1972 to 46.7 and 683.9 in 1991 in the female patients, and from 4.2 and 8.3 in
      1973 to 8.3 and 70.0 in 1991 in the male patients, respectively. Cox proportional
      hazard analysis was done to determine the effects of several covariates on
      patients and renal survival. The patients' survival rate improved, as the hazard
      ratio (HR) was decreased to 0.69 (year of diagnosis, 1982 to 1986) and to 0.48
      (year of diagnosis, 1987 to 1991) when the HR in patients diagnosed before 1981
      was taken as 1.00. Similarly, we examined renal survival by using the Cox
      proportional model. For this analysis, the date of start of dialysis therapy was
      regarded as the time of renal death. Male patients had significantly poor renal
      survival; the HR was 3.64 (95% confidence interval, 1.89 to 6.98) when the HR in
      the females was taken as 1.00. However, age at diagnosis and year of diagnosis
      did not significantly affect renal survival. The cumulated incidence of end-stage
      lupus nephritis from the time of diagnosis of systemic lupus erythematosus was
      3.1% at 5 years, 9.4% at 10 years, 15.5% at 15 years, and 21.0% at 20
      years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154492
TI  - Prevalence of antiphospholipid antibodies in nephropathies not due to systemic
      lupus erythematosus.
AB  - Renal involvement by some types of thrombotic microangiopathy has been associated
      with the presence of antiphospholipid antibodies in both patients with systemic
      lupus erythematosus (SLE) and in those with other types of connective tissue
      disorders. To assess the prevalence and clinical significance of these antibodies
      in renal disease we prospectively studied anticardiolipin antibodies and lupus
      anticoagulant activity in 138 patients. These patients were classified into four
      groups: chronic glomerulonephritis (n = 57), acute and non-SLE systemic
      nephropathies (n = 13), non-immune-related nephropathies (n = 39), and SLE
      nephropathies (n = 29). The prevalence of antiphospholipid antibodies in patients
      with chronic primary glomerulonephritis (9%) was lower than in the SLE group
      (34%) and higher, but not significantly, than in patients with non
      immunologically mediated renal diseases (2.6%). Positive patients in this group
      correspond to atypical "lupus-like" SLE forms or sporadic cases. In the group of
      patients with acute nephropathy and non-SLE systemic disorders, lupus
      anticoagulant was present in sic and anticardiolipin was present in four. In most
      cases the finding was transient and probably related to concomitant infection or
      active immune response. We conclude that there is a low prevalence of
      antiphospholipid antibodies in primary chronic glomerulonephritides, similar to
      that found in non-immunologically based nephropathies. The presence of these
      antibodies associated with chronic glomerulonephritis should raise the suspicion
      of SLE. On the other hand, positivity of these antibodies is a frequent finding
      in acute and systemic nephropathies. Therefore, the clinical and prognostic
      significance of their presence in these disorders should be further studied in a
      larger series of patients.

PMID- 8154493
TI  - Detection of hemodialysis access outlet stenosis by measuring outlet resistance.
AB  - Stenosis of the outflow segment of hemodialysis access grafts frequently leads to
      thrombosis and loss of the access. Previous studies have shown that early
      detection and correction of the stenosis can prevent graft failure. The purpose
      of the present study was to compare four methods of detecting outflow segment
      stenosis: measurement of the pressure in the venous line during dialysis,
      measurement of the pressure in the distal portion of the access graft,
      measurement of the relative resistance of the outflow segment of the graft
      relative to the total resistance of the graft, and measurement of recirculation
      of venous dialysis blood into the dialysis arterial line. The graft pressure was
      determined by measuring the pressure in the dialysis venous line with the blood
      pump turned off. The relative resistance of the outflow segment was determined by
      dividing the graft blood flow-induced pressure decrease across this segment by
      the difference between mean systemic arterial and venous pressures. Sixty-eight
      chronic hemodialysis patients were followed prospectively for 11 months. Sixty
      nine complications occurred in 31 accesses in 24 patients. Outlet obstruction was
      present in 21 of the 31 accesses. Relative graft resistance and recirculation
      rate measurement were found to be most useful in detecting hemodialysis access
      outlet obstruction.

PMID- 8154494
TI  - Infecting organisms in continuous ambulatory peritoneal dialysis patients on the
      Y-set.
AB  - Disconnect systems for performing continuous ambulatory peritoneal dialysis
      (CAPD) use a flush-before-fill technique that should theoretically reduce the
      peritonitis caused by touch contamination. However, little information about the
      infecting organisms in CAPD-related infections using disconnect systems is
      available. We performed a retrospective matched-case controlled study to define
      the organisms responsible for the peritonitis and catheter infections seen in
      CAPD patients using the Y-set without disinfectant. One hundred nineteen patients
      who began CAPD on the Y-set were matched with 119 patients who began CAPD on the
      standard spike system. Patients were matched for age, sex, race, insulin
      dependence, and time on CAPD. Infection data were prospectively collected for all
      patients. Peritonitis, exit site, and tunnel infection rates (expressed as number
      of episodes per patient-year) were all significantly lower in the Y-set patients
      (0.56 v 0.94, 0.68 v 1.08, and 0.14 v 0.22, respectively). The lower peritonitis
      rate in the Y-set patients compared with that found in the standard spike system
      patients was due to a reduction in Staphylococcus epidermidis (0.17 v 0.26, P =
      0.02), polymicrobial (0.014 v 0.06, P = 0.01), other gram-positive (0.007 v 0.09,
      P = 0.001), and sterile (0.10 v 0.19, P = 0.008) peritonitis. Rates of
      Staphylococcus aureus and gram-negative peritonitis were not different among the
      two groups. S epidermidis (0.12 v 0.23, P = 0.0014) and gram-negative (0.12 v
      0.18, P = 0.04) exit site infection rates were also lower in the Y-set
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154495
TI  - Plasmapheresis reduces proteinuria and serum capacity to injure glomeruli in
      patients with recurrent focal glomerulosclerosis.
AB  - To test the hypothesis that a circulating mediator is associated with recurrent
      idiopathic focal glomerulosclerosis (FGS), we studied the effect of
      plasmapheresis on reducing proteinuria in patients with the disease. An in vitro
      assay measured the capacity of sera before and after plasmapheresis to cause
      increased albumin permeability (P(albumin)++) in isolated rat glomeruli. Nine
      patients (five males aged 2 to 66 years) who underwent plasmapheresis for
      recurrent FGS were identified. Study variables included age, sex, time from
      diagnosis of recurrence to first pheresis, glomerular hyalinosis, complications,
      outcome, and proteinuria before and after plasmapheresis. Rat glomeruli were
      isolated in medium containing 4 g/dL bovine serum albumin, and P(albumin) was
      determined from the change in glomerular volume in response to an albumin
      gradient after incubation of the glomeruli in a 1:50 dilution of patient serum.
      Plasmapheresis reduced proteinuria from a mean of 12 +/- 7.46 g/24 hr to 5.1 +/-
      7.39 g/24 hr (P = 0.03). Six patients in whom the diagnosis was made early in the
      course of the disease and in whom plasmapheresis was initiated immediately had
      lasting remissions. Preplasmapheresis biopsies in the patients who did not
      achieve remissions showed both epithelial foot process effacement and glomerular
      sclerosis. Serum samples were available from four patients for albumin testing in
      vitro. P(albumin)++ was reduced from a mean of 0.76 +/- 0.17 before pheresis to
      0.18 +/- 0.31 after (P = 0.07). Therefore, the mechanism by which plasmapheresis
      reduces proteinuria in patients with recurrent FGS involves the decreased
      capacity of sera from these patients to injure the glomerular permeability
      barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154496
TI  - Idiopathic focal segmental glomerulosclerosis in a patient with systemic lupus
      erythematosus: an unusual combination.
AB  - Renal involvement is a major cause of morbidity in patients with systemic lupus
      erythematosus (SLE). Histologic examination of renal tissue using light
      microscopy, immunofluorescent staining, and electron microscopy permit
      identification of glomerular immune complex deposits in virtually all patients
      with SLE. We report a patient who fulfilled four American College of Rheumatology
      criteria for the classification of SLE whose clinical course was consistent with
      SLE, yet whose renal failure resulted from focal glomerulosclerosis that was not
      mediated by immune complexes. The characteristics of this case of focal
      glomerulosclerosis that differentiate it from healed focal proliferative
      glomerulonephritis are discussed.

PMID- 8154497
TI  - Frequent hemodialysis graft thrombosis: association with antiphospholipid
      antibodies.
AB  - We present two cases of patients with systemic lupus erythematosus and end-stage
      renal disease. Both were on hemodialysis and had multiple arteriovenous graft
      thromboses associated with the presence of antiphospholipid antibodies. A review
      of patients with end-stage renal disease secondary to systemic lupus
      erythematosus reveals that all had borderline or frankly elevated
      antiphospholipid antibody titers, and four of the seven patients had multiple
      graft thromboses. Possible etiologic and pathophysiologic mechanisms are
      discussed.

PMID- 8154498
TI  - High dialysate flow rate continuous arteriovenous hemodialysis: a new approach
      for the treatment of acute renal failure and tumor lysis syndrome.
AB  - A continuous dialysis technique such as continuous arteriovenous hemodialysis
      (CAVHD) could be an interesting alternative to frequent intermittent hemodialysis
      to treat acute renal failure (ARF) secondary to tumor lysis syndrome (TLS).
      However, because of massive release of intracellular solutes in TLS, CAVHD
      clearances need to be increased to treat this syndrome. Continuous arteriovenous
      hemodialysis using a high dialysate flow rate at 4 L/hr was assessed in TLS and
      ARF associated with severe hyperphosphatemia. A 0.6-m2 hollow-fiber
      polyacrylonitrile dialyzer (Multiflow 60; Hospal, St-Leonard, Quebec, Canada) was
      used. Blood urea nitrogen and serum creatinine levels decreased, respectively,
      from 102.5 to 27.2 mg/dL and from 3.1 to 1.8 mg/dL during the 36 hours of
      treatment. Serum urate concentration was normal at the beginning of treatment
      (4.5 mg/dL) and decreased to 2.1 mg/dL by the end of CAVHD. Serum phosphorus
      decreased from 16.7 to 4.4 mg/dL after the 36 hours of treatment. The calcium x
      phosphorus product decreased from 111.1 to 42.1 by 28 hours and remained under 50
      thereafter. Serum potassium was easily controlled with the addition of 2.5 mEq/L
      of KCl in dialysate and replacement solutions. No rebound increases in phosphorus
      or potassium were noted after cessation of therapy. Continuous arteriovenous
      hemodialysis clearances of urea, creatinine, phosphorus, and urate were measured
      at 2-hour intervals for the first 24 hours and at 4-hour intervals for the
      remaining 12 hours. They were 53.0 +/- 2.3 mL/min, 43.7 +/- 2.2 mL/min, 40.4 +/-
      1.9 mL/min, and 39.3 +/- 1.9 mL/min (n = 15), respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8154499
TI  - De novo diabetic glomerulosclerosis in a renal allograft recipient.
AB  - Posttransplant diabetes mellitus is a well-recognized complication of renal
      transplantation. Although such patients are at risk for the development of de
      novo diabetic glomerulosclerosis with increasing graft survival, this has rarely
      been reported. We describe a patient with posttransplant diabetes mellitus who
      developed end-stage renal failure due to diabetic glomerulosclerosis 12 years
      after renal transplantation.

PMID- 8154500
TI  - Disseminated histoplasmosis presenting as urinary tract obstruction in a renal
      transplant recipient.
AB  - Disseminated histoplasmosis occasionally involves the kidney, but the infection
      usually does not cause either urinary symptoms or a decrease in renal function.
      We present a case of disseminated histoplasmosis in a renal transplant recipient
      who presented with urinary obstruction in the allograft from a sloughed renal
      papilla infected with the fungus. At the same time the patient had chronic
      meningitis from Histoplasma capsulatum. The literature on renal involvement with
      histoplasmosis is reviewed.

PMID- 8154501
TI  - Inherited diseases of the glomerular basement membrane.
AB  - The inherited diseases of the glomerular basement membrane include Alport's
      syndrome (AS), nail-patella syndrome, and thin basement membrane nephropathy.
      Classical AS is inherited in an X-linked manner and accounts for approximately
      85% of the cases. Its manifestations include hematuria, sensorineural hearing
      loss, ocular defects, and a progression to renal failure. A defect(s) in the
      alpha 5 (IV) chain of type IV collagen is believed to be the etiology of classic
      AS, and alterations in its encoding gene localized to the X-chromosome have been
      elucidated. Although isolated cases of anti-glomerular basement membrane
      glomerulonephritis have been reported following renal transplantation in patients
      with AS, it is considered an effective form of renal replacement therapy. Less is
      known regarding the genetic basis of the autosomal-dominant form of AS, which
      apparently accounts for the remaining 15% of the cases. Nail-patella syndrome is
      characterized by nail dysplasia, patellar hypoplasia or aplasia, and nephropathy.
      It is inherited in an autosomal-dominant fashion with the gene locus assigned to
      the long arm of chromosome 9. Possible linkage between the COL5A1 gene and the
      gene for nail-patella syndrome has been suggested. Approximately 30% of the
      patients progress to end-stage renal failure. Renal transplantation has been
      successful in treating patients who progress to end-stage renal failure. Thin
      basement membrane nephropathy is an autosomal dominant trait that accounts for
      approximately 30% of the cases presenting as persistent, asymptomatic hematuria.
      The cause of thin basement membrane nephropathy is unknown at present. No decline
      in renal function is associated with thin basement membrane nephropathy.

PMID- 8154502
TI  - Elevated Lp(a) levels in patients with end-stage renal disease.

PMID- 8154503
TI  - Plasma prealbumin in hemodialysis patients.

PMID- 8154504
TI  - New imperatives for internal medicine residency education.

PMID- 8154505
TI  - Imperatives in graduate medical education in internal medicine: problem evolution
      and resolution.

PMID- 8154506
TI  - Sustained improvement in functional capacity after removal of body fluid with
      isolated ultrafiltration in chronic cardiac insufficiency: failure of furosemide
      to provide the same result.
AB  - OBJECTIVES: This study was designed to investigate whether a subclinical
      accumulation of fluid in the lung interstitium associated with moderate
      congestive heart failure interferes with the patient's functional capacity, and
      whether furosemide treatment can promote reabsorption of the excessive fluid.
      BACKGROUND: In patients with moderate congestive heart failure, pulmonary
      overhydration may be detected by chest roentgenography even if therapy is
      optimized to keep the urinary output normal and to prevent weight gain and
      dependent edema formation. Removal of the overhydration may help define its
      significance. METHODS: Patients, whose regimens of digoxin, oral furosemide, and
      angiotensin-converting enzyme (ACE) inhibitor therapy were kept constant, were
      randomly allocated to receive ultrafiltration (8 cases) or an intravenous bolus
      of supplemental furosemide (mean dose: 248 mg; 8 cases). The amount of body fluid
      removed with each method approximated 1600 mL. Functional performance was
      assessed with cardiopulmonary exercise tests. RESULTS: Soon after fluid
      withdrawal by either method, the filling pressures of the two ventricles and body
      weight were reduced and plasma renin activity, norepinephrine, and aldosterone
      were augmented. After furosemide administration, hormone levels remained elevated
      for the next 4 days, and during this period, patients had positive water
      metabolism, recovery of the elevated ventricular filling pressures, and re
      occurrence of lung congestion with no improvement in functional capacity. After
      ultrafiltration, levels of renin, norepinephrine, and aldosterone fell to below
      control values within the first 48 hours and water metabolism was equilibrated at
      a new set point (less fluid intake and diuresis without weight gain). The
      favorable circulatory and ventilatory adjustments consequent to the reabsorption
      of lung water improved the functional capacity of these patients. That may also
      have restored the lung's ability to clear norepinephrine, thus restraining its
      facilitation of renin release. The improvement continued 3 months after the
      procedure. CONCLUSIONS: In patients with congestive heart failure the set point
      of fluid balance is altered in spite of oral furosemide therapy; supplemental
      intravenous furosemide does not shift the set point, at least not when combined
      with ACE inhibition. Excessive, although asymptomatic, lung water limits the
      functional capacity of the patient.

PMID- 8154507
TI  - New criteria for diagnosis of infective endocarditis: utilization of specific
      echocardiographic findings. Duke Endocarditis Service.
AB  - PURPOSE: This study was designed to develop improved criteria for the diagnosis
      of infective endocarditis and to compare these criteria with currently accepted
      criteria in a large series of cases. PATIENTS AND METHODS: A total of 405
      consecutive cases of suspected infective endocarditis in 353 patients evaluated
      in a tertiary care hospital from 1985 to 1992 were analyzed using new diagnostic
      criteria for endocarditis. We defined two "major criteria" (typical blood culture
      and positive echocardiogram) and six "minor criteria" (predisposition, fever,
      vascular phenomena, immunologic phenomena, suggestive echocardiogram, and
      suggestive microbiologic findings). We also defined three diagnostic categories:
      (1) "definite" by pathologic or clinical criteria, (2) "possible," and (3)
      "rejected." Each suspected case of endocarditis was classified using both old and
      new criteria. Sixty-nine pathologically proven cases were reclassified after
      exclusion of the surgical or autopsy findings, enabling comparison of clinical
      diagnostic criteria in proven cases. RESULTS: Fifty-five (80%) of the 69
      pathologically confirmed cases were classified as clinically definite
      endocarditis. The older criteria classified only 35 (51%) of the 69
      pathologically confirmed cases into the analogous probable category (p < 0.0001).
      Twelve (17%) pathologically confirmed cases were rejected by older clinical
      criteria, but none were rejected by the new criteria. Seventy-one (21%) of the
      remaining 336 cases that were not proven pathologically were probable by older
      criteria, whereas the new criteria almost doubled the number of definite cases,
      to 135 (40%, p < 0.01). Of the 150 cases rejected by older criteria, 11 were
      definite, 87 were possible, and 52 were rejected by the new criteria. CONCLUSION:
      Application of the proposed new criteria increases the number of definite
      diagnoses. This should be useful for more accurate diagnosis and classification
      of patients with suspected endocarditis and provide better entry criteria for
      epidemiologic studies and clinical trials.

PMID- 8154508
TI  - Evaluation of new clinical criteria for the diagnosis of infective endocarditis.
AB  - PURPOSE: The clinical diagnosis of infective endocarditis (IE) can be difficult.
      A new diagnostic schema for IE (the Duke criteria) has been proposed, utilizing
      clinical, microbiologic, and echocardiographic data. We evaluated the Duke
      criteria in a cohort of prospectively enrolled patients suspected of having IE
      and compared the diagnostic efficiency of these criteria with the previously
      published criteria of von Reyn. PATIENTS: Sixty-three febrile patients with
      suspected IE at a non-referral, municipal hospital were evaluated. All patients
      had the following parameters defined: the presence and nature of underlying heart
      disease; recent abuse of intravenous drugs; peripheral stigmata of IE; blood
      culture results; findings on two-dimensional transthoracic and transesophageal
      echocardiography (TTE, TEE); and the results of open heart surgery. RESULTS:
      Twelve of 63 patients underwent open heart surgery, at which time IE was
      pathologically confirmed in 10 patients and excluded in 2 patients. All 10
      patients with pathologically confirmed IE were classified as "clinically
      definite" by Duke criteria, whereas 5 of 10 were rejected by von Reyn criteria (p
      < 0.05). Among the remaining 51 patients suspected of IE and evaluated by both
      von Reyn and Duke clinical criteria, significantly more cases were classified as
      "definite" IE by Duke criteria than by von Reyn criteria (p < 10(-5)). Similarly,
      significantly fewer cases were rejected as IE by the Duke criteria as compared
      with the von Reyn criteria (p < 10(-6). Duke criteria were also significantly
      better at diagnosing IE than von Reyn criteria in the following clinical
      settings: suspected right-sided IE (p < 0.01); suspected left-sided IE (p =
      0.014); suspected culture-negative IE (p < 10(-2); and IE complicating
      Staphylococcus aureus or viridans streptococcal bacteremias (p < 10(-5); p <
      0.05, respectively). Among 30 cases defined as clinically definite by the Duke
      criteria, the presence of blood culture positivity and echocardiographically
      defined vegetations was important in this classification of 77% and 57% of cases,
      respectively. Among the 17 patients in the clinically definite category with
      vegetative endocarditis observed by echocardiography, 7 (41%) had vegetations
      defined only by TEE. CONCLUSION: The Duke criteria are superior to the von Reyn
      criteria for the clinical diagnosis of IE, predominantly reflecting use of two
      dimensional echocardiographic demonstration of valvular vegetations in the Duke
      schema.

PMID- 8154509
TI  - Case definitions for infective endocarditis.

PMID- 8154510
TI  - The clinical evaluation of patients with subclinical hyperthyroidism and free
      triiodothyronine (free T3) toxicosis.
AB  - PURPOSE: To develop a strategy to identify cases of endogenous subclinical
      hyperthyroidism and free triiodothyronine (free T3) thyrotoxicosis in otherwise
      healthy ambulatory patients. PATIENTS AND METHODS: In a retrospective study we
      reviewed the records of ambulatory patients who had thyroid stimulating hormone
      (TSH) levels determined between October 1, 1991 and August 31, 1992. Each patient
      also had a simultaneous free thyroxine (free T4) measurement. Patients were
      excluded from consideration if they had active, concurrent non-thyroidal illness,
      psychiatric disease, known hypothalamic/pituitary lesions, were under treatment
      for hyper- or hypothyroidism, were on drugs known to affect TSH levels, or were
      pregnant. Patients without exclusions were diagnosed with free T3 toxicosis if
      they had: (1) a markedly subnormal TSH level (less than or equal to 0.1 mU/L),
      (2) a normal free T4, (3) a normal total T3, (4) evidence of a primary thyroid
      abnormality (e.g., autonomous function on a thyroid scan), and (5) an elevated
      free T3 level by tracer equilibrium dialysis. Patients meeting conditions 1-4,
      but with normal free T3 levels, were considered to have subclinical
      hyperthyroidism. RESULTS: One thousand twenty-five patients had TSH and
      simultaneous free T4 determinations, and 148 of these had markedly subnormal TSH
      but normal free T4 levels. Three patients met the criteria for free T3 toxicosis
      and three had subclinical hyperthyroidism. All six patients had either
      multinodular glands or a single nodule on thyroid exam. Four patients were
      treated with radioactive iodine or surgery, resulting in reversal of the TSH
      suppression in three cases. CONCLUSION: Apparently healthy ambulatory patients
      with subnormal TSH levels should be worked up with measurements of free T4 and
      total T3. If these are normal, a T3 level (by tracer equilibrium dialysis) be
      obtained to distinguish subclinical hyperthyroidism from overt free T3 toxicosis.
      A thyroid scan and radioiodine uptake measurement can be obtained to substantiate
      the diagnosis. Some patients with these conditions will benefit from treatment.

PMID- 8154511
TI  - Effects of commonly prescribed nonsteroidal anti-inflammatory drugs on thyroid
      hormone measurements.
AB  - PURPOSE: To assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs)
      on thyroid function tests. PATIENTS AND METHODS: Eighty-nine patients receiving
      NSAIDs and 22 control subjects not taking NSAIDs were studied in a cross
      sectional survey at Veterans Affairs and University hospitals. Measurements of
      serum thyroxine (T4), free T4 index, triiodothyronine (T3), and thyrotropin
      (thyroid-stimulating hormone [TSH]) were obtained for all subjects. RESULTS:
      Serum T4 measurements were lowered only in salsalate-treated patients, while
      serum T3 was depressed in patients receiving salsalate, diclofenac sodium, and
      naproxen. Serum T4 and T3 were unchanged in patients treated with diflunisal,
      ibuprofen, indomethacin, piroxicam, or sulindac. Serum TSH was normal in all
      subjects. CONCLUSIONS: Several NSAIDs can lower serum thyroid hormone
      concentrations, principally by interfering with the binding of T4 and T3 to serum
      carrier proteins; patients taking these drugs remain euthyroid. Awareness of
      these interactions may prevent unnecessary diagnostic or therapeutic
      interventions.

PMID- 8154512
TI  - Sensitivity of serum methylmalonic acid and total homocysteine determinations for
      diagnosing cobalamin and folate deficiencies.
AB  - PURPOSE: Patients with cobalamin (vitamin B12) deficiency usually lack many of
      the classic features of severe megaloblastic anemia; because of the low
      diagnostic specificity of decreased serum cobalamin levels, demonstrating the
      deficiency unequivocally is often difficult. We examined the sensitivity of
      measuring serum concentrations of methylmalonic acid and total homocysteine for
      diagnosing patients with clear-cut cobalamin deficiency and compared the results
      with those of patients with clear-cut folate deficiency. PATIENTS AND METHODS:
      Serum metabolites were measured for all patients seen from 1982 to 1989 at two
      university hospitals who met the criteria for cobalamin and folate deficiency
      states and for such patients seen from 1968 to 1981 from whom stored sera were
      available. In all, 406 patients had 434 episodes of cobalamin deficiency and 119
      patients had 123 episodes of folate deficiency. Criteria for deficiency states
      included serum vitamin levels, hematologic and neurologic findings, and responses
      to therapy. Responses were documented in 97% of cobalamin-deficient patients and
      76% of folate-deficient patients. Metabolite levels were measured by modified
      techniques using capillary-gas chromatography and mass spectrometry. RESULTS:
      Most of the cobalamin-deficient patients had underlying pernicious anemia; two
      thirds were blacks or Latinos. Hematocrits were normal in 28% and mean cell
      volumes in 17%. Of the 434 episodes of cobalamin deficiency, 98.4% of serum
      methylmalonic acid levels and 95.9% of serum homocysteine levels were elevated
      (greater than 3 standard deviations above the mean in normal subjects). Only one
      patient had normal levels of both metabolites. Serum homocysteine levels were
      increased in 91% of the 123 episodes of folate deficiency. Methylmalonic acid was
      elevated in 12.2% of the folate-deficient patients; in all but one, the elevation
      was attributable to renal insufficiency or hypovolemia. CONCLUSIONS: For the
      cobalamin-deficient patients, measuring serum metabolite concentrations proved to
      be a highly sensitive test of deficiency. We conclude that normal levels of both
      methylmalonic acid and total homocysteine rule out clinically significant
      cobalamin deficiency with virtual certainty.

PMID- 8154513
TI  - Occurrence, etiology, and clinical significance of extreme thrombocytosis: a
      study of 280 cases.
AB  - PURPOSE: To determine the etiology and to evaluate the clinical consequences of
      an extremely elevated platelet count. PATIENTS AND METHODS: A review of the
      medical records was performed on all patients encountered during a 5 1/2-year
      period who had at least one platelet count of 1,000 x 10(9)/L or greater.
      RESULTS: Of the total of 280 patients with extreme thrombocytosis (EXT), 231
      (82%) had reactive thrombocytosis (RT), 38 (14%) had a myeloproliferative
      disorder (MPD), and 11 (4%) had cases of uncertain etiology. RT was more common
      than MPD in all age groups except those in the eighth decade and older. Symptoms
      of bleeding and/or vaso-occlusive phenomena were noted in association with EXT in
      21 (56%) of the MPD patients but in only 10 (4%) of the RT patients. Treatment to
      lower the platelet count and/or inhibit platelet function was employed in 36 MPD
      patients and 23 RT patients. Eight patients with MPD and 34 with RT are known to
      have died, but no patient in either group is known to have died of a thrombotic
      or bleeding event when the platelet count was greater than or equal to 1,000 x
      10(9)/L. CONCLUSIONS: Platelet counts greater than or equal to 1,000 x 10(9)/L
      should not be considered rare events in the general, acute-care hospital
      population, and usually represent a reactive phenomenon.

PMID- 8154514
TI  - Effect of prednisone and hydroxychloroquine on coronary artery disease risk
      factors in systemic lupus erythematosus: a longitudinal data analysis.
AB  - PURPOSE: To determine the effect of prednisone dose and hydroxychloroquine dose
      on the coronary artery disease risk factors serum cholesterol level, mean
      arterial blood pressure, and weight in patients with systemic lupus
      erythematosus. PATIENTS AND METHODS: A longitudinal cohort study of 264 patients
      with systemic lupus erythematosus was conducted. For all patients in the cohort,
      serum cholesterol, mean arterial pressure, weight, prednisone dose,
      hydroxychloroquine dose, and other potential confounding variables were recorded
      at each visit. Regression analysis appropriate for longitudinal data was used to
      assess the effect of prednisone on serum cholesterol and mean arterial pressure.
      To assess the effect of prednisone on weight, patients' weights were compared 90
      days before and after a 10-mg or 20-mg increase in prednisone. RESULTS: A total
      of 3,027 patient visits were analyzed. In the regression model for serum
      cholesterol, a change in prednisone dose of 10 mg was associated with a change in
      cholesterol of 7.5 +/- 1.46 (SE) mg% after adjustment for the other significant
      variables in the model, including sex, race, hydroxychloroquine dose, and
      proteinuria. In the regression model for hydroxychloroquine, the 200-mg and the
      400-mg dose were both associated with lower serum cholesterol (8.9 +/- 3.44 SE
      mg%). In the regression model for mean arterial blood pressure, a 10-mg change in
      prednisone dose led to a change in mean arterial blood pressure of 1.1 mm Hg
      after adjustment for age, weight, and antihypertensive drug use. A 10-mg increase
      in prednisone dose was associated with a mean weight change of 5.50 +/- 1.23 (SE)
      lb. CONCLUSIONS: Changes in prednisone dose led to definable changes in risk
      factors for coronary artery disease, even after adjustment for other variables
      known to affect these risk factors. According to longitudinal regression
      analysis, hydroxychloroquine therapy was associated with lower serum cholesterol.

PMID- 8154515
TI  - Diabetes mellitus: a disease of abnormal cellular calcium metabolism?
AB  - Although the pathogenesis of the diabetes mellitus syndrome remains poorly
      understood, both insulin-dependent diabetes mellitus and non-insulin-dependent
      diabetes mellitus predispose the individual to a similar spectrum of
      complications, including hypertension, macrovascular and microvascular disease,
      cataracts cardiomyopathy, neuropathy, and premature aging, suggesting that these
      complications develop along a pathway common to both diabetic conditions. Yet not
      all diabetic persons are affected by all of these complications or to the same
      degree. What causes this marked variability in the clinical manifestations of the
      diabetes syndrome remains an enigma. Accumulating data from animal models of
      diabetes and from studying patients with diabetes reveal that intracellular
      calcium levels are increased in most tissues. The activities of the membrane,
      adenosine triphosphatase (ATPase) associated cation pumps, which determine
      intracellular calcium level (i.e., calcium-ATPase and [sodium + potassium]
      ATPase), are also altered. The nature of the alteration is often tissue specific
      and may depend on the level of blood glucose or insulin, or both. In this review
      we discuss the potential contribution of these changes in intracellular calcium
      regulation, whether acquired or genetically determined, to the pathogenesis of
      the diabetes syndrome, to the abnormalities in insulin secretion and action
      (mainly in non-insulin-dependent diabetes), and to the complications of both
      diabetes syndromes. Altered intracellular calcium metabolism may represent a
      common, underlying abnormality linking the metabolic, cardiovascular, ocular, and
      neural manifestations of the diabetic disease process.

PMID- 8154516
TI  - Gastrointestinal complications of nonsteroidal anti-inflammatory drugs:
      prophylactic and therapeutic strategies.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used
      drugs in the Western world. Patients undergoing NSAID therapy often experience
      abdominal discomfort, and some of them develop serious complications, such as
      ulceration, perforation, or bleeding. Since serious complications of NSAID
      therapy can occur in relatively asymptomatic patients and abdominal symptoms do
      not serve as a signal of impending difficulties, there is a need for methods to
      identify those patients who may benefit from prophylactic therapy to prevent
      NSAID-induced injury. Therapy to prevent NSAID-associated gastrointestinal
      ulcerations is most effective when prostaglandins are used. H2-receptor
      antagonists prevent duodenal ulcerations but not gastric ulcerations. The role of
      omeprazole (hydrogen-potassium pump inhibitor) and sucralfate in the prevention
      of gastroduodenal ulcerations has not been firmly established. Healing of
      existing ulcerations in the face of continuing therapy with NSAIDs is marginally
      accelerated by H2-receptor antagonists, but the rate of healing in the presence
      of continued NSAID therapy is much slower than when NSAIDs are discontinued.
      Omeprazole may prove to accelerate the healing of NSAID-associated ulcerations
      even when NSAID therapy is continued, but more information is needed to
      substantiate this possibility. New methods are needed for early noninvasive
      detection of mucosal damage by NSAIDs and for the identification of individuals
      who should receive prophylactic therapy. New agents are also needed to provide
      cost-effective prophylaxis against the development of ulcerations and serious
      complications from NSAIDs.

PMID- 8154517
TI  - Acquired immunodeficiency syndrome and the Americans with Disabilities Act: a
      legal duty to treat.
AB  - The emergence of the human immunodeficiency virus (HIV) as a serious public
      health threat has rekindled long dormant debate about individual physicians' duty
      to treat potentially contagious patients. Because of the widely accepted common
      law tenet of the "no duty [to treat] rule," previous work on a duty to treat
      focused on historical reviews, medical society position statements, and the
      ethical arguments upon which the statements are based. The passage of the
      Americans with Disabilities Act has rendered these discussions moot by creating,
      through federal civil rights mechanisms, a legal duty to treat patients with HIV,
      enforceable under considerable penalties. The paper also concludes that there has
      been inadequate attention paid to similar civil rights concerns of infected
      physicians.

PMID- 8154518
TI  - Acute renal failure in a 59-year-old man.

PMID- 8154519
TI  - Increased serum creatinine in the absence of renal failure in profound
      hypothyroidism.

PMID- 8154520
TI  - Platelet GPIIb/IIIa antagonists: how safe is this antithrombotic approach?

PMID- 8154521
TI  - Lovastatin and myopathy.

PMID- 8154522
TI  - Chagas disease: another cause of cerebral mass in AIDS.

PMID- 8154523
TI  - Incidence of various types of retinal vein occlusion and their recurrence and
      demographic characteristics.
AB  - We analyzed data on 1,108 patients (1,229 eyes) with various types of retinal
      vein occlusion. Retinal vein occlusion was classified into six distinct clinical
      types: (I) nonischemic and (II) ischemic central retinal vein occlusion, (III)
      nonischemic and (IV) ischemic hemicentral retinal vein occlusion, and (V) major
      and (VI) macular branch retinal vein occlusion. Retinal vein occlusion occurred
      more often in men than women. The age range of patients was between 14 and 92
      years, with 570 of 1,108 patients (51%) 65 years or older; however, 99 of 620
      (16%), 15 of 154 (10%), and 17 of 375 (5%) of the patients with central,
      hemicentral, and branch retinal vein occlusion, respectively, were younger than
      45 years. The cumulative probability of developing a second episode of the same
      or a different type of retinal vein occlusion in the same eye was 0.9% within two
      years and 2.5% within four years, and in the fellow eye was 7.7% and 11.9%,
      respectively. The cumulative probability of conversion of nonischemic to ischemic
      central retinal vein occlusion at six months and 18 months was 13.2% and 18.6%,
      respectively, in persons 65 years of age or older and 6.7% and 8.1%,
      respectively, in persons 45 to 64 years of age.

PMID- 8154524
TI  - Finding the retinal hole in the pseudophakic eye with detachment.
AB  - The recently developed wide-field indirect contact lenses, recommended and used
      for pancoagulation of the retina posterior to the equator, have proved to be
      unexpectedly advantageous for finding retinal breaks anterior to the equator in
      the pseudophakic eye. Through a 6-mm pupil, it is possible with some ocular
      rotations, tilting of the lens, and scleral depression to bring into view the
      retina anterior to the equator and frequently the ora serrata. We found or
      confirmed 45 small retinal breaks anterior to the equator in 24 retinal
      detachments in pseudophakic eyes with the wide-field indirect contact lens. The
      indirect contact lens eliminates the blur that occurs when viewing through the
      edge of the intraocular lens, and its image suffers less interference from lens
      and capsular opacities.

PMID- 8154525
TI  - Two cases of intraocular infection with Alaria mesocercaria (Trematoda)
AB  - We encountered two cases of human intraocular infection with mesocercariae of
      Alaria (Trematoda), involving unrelated Asian men who had unilateral decreased
      vision. Both patients had pigmentary tracks in the retina, areas of active or
      healed retinitis, or both, and other signs of diffuse unilateral subacute
      neuroretinitis. Similar, nonnematode worms were seen in the patients' retinas and
      vitreous, respectively, several years after apparent infection. The worm in Case
      1 was analyzed from projected fundus photographs and diagnosed as an Alaria
      mesocercaria on the basis of its shape, size (500 x 150 microns), and movement;
      it was successfully killed with laser. The worm in Case 2 was removed surgically
      from the vitreous and identified as A. mesocercaria, 555 x 190 microns, most
      likely A. americana. The probable source of infection in the patients was
      ingestion, in local restaurants, of undercooked frogs' legs containing A.
      mesocercaria. In addition to causing prolonged intraocular infection, A.
      mesocercaria was found to be a cause of diffuse unilateral subacute
      neuroretinitis, a condition previously attributed only to intraocular nematode
      larvae.

PMID- 8154526
TI  - Excimer retreatment of regression after photorefractive keratectomy.
AB  - Regression of effect is a well-established complication of excimer laser
      photorefractive keratectomy for the correction of myopia. In 17 eyes retreated
      with excimer photorefractive keratectomy, minimum follow-up time was six months.
      Mean (+/- SD) refraction at six months postoperatively was -0.97 +/- 2.10
      diopters, significantly different (P < .01) from the pre-retreatment mean of 
      2.91 +/- 0.86 diopters. The 11 best eyes (six-month refraction < -1.00 diopter)
      had a mean refraction of +0.32 +/- 0.67 diopter. At six months after retreatment,
      64.7% had an uncorrected visual acuity greater than or equal to 20/40, and 58.8%
      were within 1.00 diopter of emmetropia. Two eyes showed a loss of one to two
      Snellen lines at six months. There was no significant increase in mean haze after
      retreatment. While the percentage of eyes with uncorrected visual acuity greater
      than or equal to 20/40 and the percentage of eyes within 1.00 diopter of
      emmetropia were lower than in eyes which did not require retreatment, the results
      of this study indicate that the majority of photorefractive keratectomy
      regressions can be successfully retreated.

PMID- 8154527
TI  - Keratitis as a complication of bilateral, simultaneous radial keratotomy.
AB  - During a one-month period, we examined four patients referred for evaluation of
      probable microbial keratitis after bilateral, simultaneous radial keratotomy.
      Each patient had midstromal infiltrates compatible with microbial keratitis that
      involved one or more of the radial incisions. In two patients the keratitis was
      bilateral. All patients had been treated empirically with antibiotic agents;
      superficial cultures with cotton-tipped applicators and corneal scraping by
      inserting a platinum spatula into the radial incisions were negative. Corneal
      biopsy of one patient disclosed gram-positive rods and culture of the biopsy
      specimen grew diphtheroids. The infiltrates gradually resolved over a period of
      several months with intensive antibiotic therapy. Sight-threatening infectious
      keratitis can occur after radial keratotomy, and we believe that simultaneous
      bilateral ocular surgery of any kind should be discouraged.

PMID- 8154528
TI  - Linear endotheliitis.
AB  - We treated six eyes of five patients with linear endotheliitis. This entity
      appears clinically as a line of keratic precipitates on the corneal endothelium
      that progresses centrally and is accompanied by peripheral stromal and epithelial
      edema. All five patients had ocular pain, redness, and photophobia. One eye had
      an episode of a dendritic lesion typical of herpes simplex. Two eyes had a
      history of cataract extraction before developing linear endotheliitis. We treated
      all patients aggressively with a combination of corticosteroids and antiviral
      agents. Complete resolution of inflammation and edema occurred in all cases. Four
      patients required the use of oral acyclovir to control the inflammation and
      prevent recurrence of the disease. Linear endothelitis is a distinct form of
      endotheliitis that may be associated with herpes simplex virus, and treatment
      included corticosteroid and antiviral therapy.

PMID- 8154529
TI  - Acanthamoeba sclerokeratitis.
AB  - We treated a healthy soft contact lens wearer who developed Acanthamoeba
      sclerokeratitis in the left eye. The patient had severe pain and ring-shaped
      subepithelial infiltrates. The keratitis progressed and scleral nodules developed
      despite aggressive treatment with topical clotrimazole, dibromopropamidine
      isethionate, and corticosteroids. Corneal transplantation and cryotherapy were
      performed. The corneal button demonstrated Acanthamoeba cysts. Cultures of biopsy
      specimens taken from two different scleral nodules at two separate times were
      positive for Acanthamoeba. The disease progressed despite a second corneal graft
      and the addition of polyhexamethylene biguanide eyedrops. Enucleation of the left
      eye was required. Histopathologic examination of the specimen documented an
      Acanthamoeba cyst associated with a granulomatous inflammatory response deep in
      the sclera. Acanthamoeba scleritis may be associated with a poor prognosis, even
      with intensive medical and surgical treatment.

PMID- 8154530
TI  - Vaccinia keratouveitis manifesting as a masquerade syndrome.
AB  - A patient who used contact lenses and had a history of blunt trauma developed
      vaccinia keratouveitis after accidental ocular autoinoculation from a recent
      vaccination site. Corneal and conjunctival cultures were taken for bacteria,
      fungi, Acanthamoeba, and viruses. Viral-like cytopathic effects became evident in
      tissue culture within three days. Immunofluorescence studies were negative for
      varicella-zoster virus, herpes simplex virus, adenovirus, measles, mumps,
      parainfluenza, and influenza. Pox viral particles were identified in the infected
      tissue cultures by electron microscopy. The Hind III restriction endonuclease
      profile of the viral DNA isolate was similar to the Lister strain of vaccinia
      virus. Ocular vaccinia may manifest as a masquerade syndrome and may mimic signs
      of herpes simplex virus, varicella-zoster virus, and Acanthamoeba infection.
      Although vaccination with vaccinia is currently limited to a few populations
      throughout the world, vaccinia must still be considered in the differential
      diagnosis of infectious keratouveitis.

PMID- 8154531
TI  - Efficacy of lodoxamide 0.1% ophthalmic solution in resolving corneal
      epitheliopathy associated with vernal keratoconjunctivitis.
AB  - A multicenter, randomized, double-masked, parallel-group study compared the long
      term efficacy and safety of lodoxamide 0.1% ophthalmic solution and placebo in
      118 patients with vernal keratoconjunctivitis. The test drugs were instilled four
      times daily for 90 days. Lodoxamide 0.1% ophthalmic solution was significantly (P
      < .05) more effective than placebo in lowering severity scores for epithelial
      disease and corneal staining, evidence of the superior efficacy of lodoxamide
      0.1% ophthalmic solution in reversing the corneal complications commonly
      associated with moderate to severe vernal keratoconjunctivitis. Additionally,
      lodoxamide 0.1% ophthalmic solution ameliorated the other key signs of vernal
      keratoconjunctivitis, including upper tarsal papillae, limbal signs (papillae,
      hyperemia, and Trantas' dots), and conjunctival discharge. The between-group
      differences in the relief of symptoms (itching, tearing, and photophobia) were
      clinically significant but not always statistically significant. Treatment
      related adverse events were reported with similar frequency in both treatment
      groups, and none were serious.

PMID- 8154532
TI  - Group B streptococcal metastatic endophthalmitis.
AB  - Reports of invasive Group B Streptococcus infection in adults with underlying
      medical conditions have been increasing. Ocular infection with this organism is
      unusual. Metastatic endophthalmitis in adults caused by this organism has been
      reported rarely and has only been associated with endocarditis. We encountered
      two cases of Group B streptococcal metastatic endophthalmitis in adults who did
      not have endocarditis. These cases reflect the increasing incidence of invasive
      Group B Streptococcus infection with its varying manifestations. Additionally,
      they emphasize the importance of considering this pathogen as a cause of
      metastatic endophthalmitis in adults with predisposing illnesses.

PMID- 8154533
TI  - The context and consequences of ocular injuries from air guns.
AB  - There is little available information on the context of air-gun inflicted ocular
      injuries. To address this need, we performed a systematic telephone survey of
      victims of severe air-gun ocular injuries, collected between January 1986 and
      August 1992, through the auspices of the National Eye Trauma System and the
      Alabama Eye Injury Registry. One hundred forty interviews were completed with
      injury victims or their parents. Pump-action rifles with BB ammunition were the
      most common weapons. Victims and shooters were predominantly male (91% and 89%,
      respectively) and their mean age was 13 years. Of the injuries, 95% were
      inflicted by individuals known to the victim; 40% of these were relatives. People
      were the intended targets in 45% of the injuries. Ricochets accounted for 26% of
      the injuries. Of those victims with penetrating injuries, 84% had visual acuity
      less than 20/200 despite numerous surgical attempts. Adults were present at the
      scene of the injury in only 11% of the incidents, implying that unrestricted
      access to these weapons by children is likely the principal risk factor for
      injury.

PMID- 8154534
TI  - Combined keratoplasty, cataract extraction, and intraocular lens implantation
      after corneolenticular laceration in children.
AB  - Over a period of two years we performed combined penetrating keratoplasty,
      cataract extraction, and intraocular lens implantation in seven children between
      the ages of 2 and 12 years old. The interval between trauma and the surgery
      varied from six weeks to six months (3.5 +/- 1.6 months, mean +/- SD). All of the
      patients had undergone primary repair of corneal perforation. Fresh corneas
      preserved in McCarey-Kaufman medium were used. The graft size was 7.5 mm with 0.5
      mm disparity. Posterior chamber polymethylmethacrylate C-loop lenses were used in
      all cases. The surgeon's average postkeratoplasty keratometry was used in the
      calculation of intraocular lens power. The follow-up period ranged from nine to
      36 months (18 +/- 9.1 months, mean +/- SD). Six grafts remained clear at the
      final follow-up. The visual acuity ranged from 20/40 to 20/200 with final
      astigmatism ranging from 0.5 diopter to 2.0 diopters. One patient developed a
      retinal detachment 12 months after surgery, which was successfully reattached.
      One patient, who had preoperative corneal vascularization, had graft rejection,
      which was treated medically. Our limited series suggests that the triple ocular
      procedure is a good choice for the treatment of corneolenticular trauma in
      children. The proper postoperative treatment includes vigorous antiamblyopia
      therapy and Nd:YAG laser treatment of after-cataracts.

PMID- 8154535
TI  - Anterior polar cataract in two sisters with an unbalanced 3;18 chromosomal
      translocation.
AB  - Congenital anterior polar cataracts can be associated with chromosomal
      abnormalities. We treated two sisters with this condition who had the same
      unbalanced translocation between the long arm of chromosome 3 and the short arm
      of chromosome 18. Their mother had a balanced translocation between those
      chromosomes but had no cataract. Both sisters had dysmorphic features. Their
      genetic status resulted in partial trisomy of the long arm of chromosome 3 and
      partial monosomy of the short arm of chromosome 18. To aid in the identification
      of specific cataract genes, patients with chromosomal abnormalities should have
      careful ophthalmic examinations, and their lenticular findings should be
      reported.

PMID- 8154536
TI  - Familial uveal melanoma.
AB  - Because familial occurrences of uveal melanoma are rare, there have only been 15
      cases of familial melanoma reported in the literature. We studied 11 additional
      families with a total of 24 members, in which two or more members were afflicted
      with uveal melanoma. The median age at diagnosis was 56.5 years, similar to the
      median age at diagnosis of the remaining patients treated in our institution.
      Thirteen were male and 11 were female, which is consistent with the slight
      predominance of males found in many large surveys of patients with uveal
      melanoma. There is a possibility of a heritable component present in these
      families.

PMID- 8154538
TI  - Ocular amyloidosis.

PMID- 8154537
TI  - Quantitative assessment of the blood-aqueous barrier in human eyes with malignant
      or benign uveal tumors.
AB  - We assessed alterations of the blood-aqueous barrier in 43 eyes with malignant
      melanoma (31 choroidal and 12 ciliary body), 40 eyes with benign uveal tumors,
      and 199-age matched normal control eyes. Aqueous flare was quantified with the
      laser flare-cell meter and correlated with clinical and histopathologic findings.
      Aqueous flare (photon counts/ms) was significantly higher in melanoma eyes (20.91
      +/- 12.40) than in eyes with benign tumors (4.26 +/- 1.55) (P < .0001) and normal
      control eyes (3.99 +/- 1.14) (P < .0001). In melanoma eyes, clinical and
      histologic findings associated with significantly increased aqueous flare values
      were as follows: tumor height, serous retinal detachment, tumor necrosis,
      lymphocytic tumor infiltration, and tumor hemorrhage. Development and growth of
      uveal melanomas are accompanied by marked alterations of the blood-aqueous
      barrier. The noninvasive laser flare-cell meter may give useful additional
      information about malignant and benign uveal tumors.

PMID- 8154539
TI  - Two-port vitrectomy for vitreous loss during sutureless cataract surgery.

PMID- 8154540
TI  - Transient cataract after scleral buckling in myopic pseudophakia.

PMID- 8154541
TI  - Choroiditis in systemic lupus erythematosus.

PMID- 8154542
TI  - Varicella-zoster virus retinitis as the initial manifestation of the acquired
      immunodeficiency syndrome.

PMID- 8154543
TI  - Septic cavernous sinus thrombosis after head trauma.

PMID- 8154544
TI  - Intraorbital glomus cell tumor.

PMID- 8154545
TI  - Imaging of cyclodialysis cleft by ultrasound biomicroscope.

PMID- 8154546
TI  - Band-shaped, whorled microcystic corneal dystrophy.

PMID- 8154547
TI  - Deep Alternaria keratomycosis with intraocular extension.

PMID- 8154548
TI  - Exclusion of chromosome 11q13 region as a genetic locus responsible for autosomal
      dominant Stargardt's disease.

PMID- 8154549
TI  - Unintentional childhood injury--where the buck should stop.

PMID- 8154550
TI  - Reducing violence--how do we proceed?

PMID- 8154551
TI  - Firearm-related violence--what we don't know is killing us.

PMID- 8154552
TI  - The report of the Surgeon General: preventing tobacco use among young people.
AB  - This year's surgeon general's report on smoking and health is the first such
      report to focus on young people. From extensive data that indicate that tobacco
      use is a pediatric epidemic, the report reached six major conclusions: (1) Nearly
      all first use of tobacco occurs by age 18. (2) Most adolescent smokers are
      addicted to nicotine. (3) Tobacco is often the first drug used by young people
      who subsequently use illegal drugs. (4) There are identified psychosocial risk
      factors for the onset of tobacco use. (5) Cigarette advertising also appears to
      increase young people's risk of smoking. (6) Communitywide efforts have
      successfully reduced adolescent use of tobacco. This commentary restates each of
      the six conclusions, summarizes the data that support each, and then considers
      the implications of the conclusions for public health action.

PMID- 8154553
TI  - Medicaid reimbursement--can we save money by paying doctors more?

PMID- 8154554
TI  - Commentary: Lessons from Medicaid--improving access to office-based physician
      care for the low-income population.
AB  - Medicaid offers important lessons about providing access to office-based
      physician services for the poor. First, differentials in physician fees between
      Medicaid and other payers compromise access to care and are difficult to reverse.
      Second, managed care alone is not enough to attain equity in access, especially
      if differentials in payment rates between Medicaid and private patients in
      managed care settings are allowed to grow. Finally, financing strategies alone
      are not sufficient to resolve the shortage of health care providers in medically
      underserved areas. In these areas, payment policy must be combined with resource
      development to ensure that vulnerable populations have access to care.

PMID- 8154555
TI  - Medicaid physician payment reform: using the Medicare Fee Schedule for Medicaid
      payments.
AB  - OBJECTIVES: The purpose of this article is to provide estimates of the costs of
      basing Medicaid physician payment levels on the new resource-based Medicare Fee
      Schedule. Two possible policy options are considered: setting all Medicaid
      physician fees at the Medicare Fee Schedule level and setting only office visit
      fees at the new Medicare levels. METHODS: Data on Medicaid physician fees, use
      patterns, and the Medicare Fee Schedule are used to develop state-level estimates
      of expenditure changes under each option. RESULTS: Setting Medicaid rates at the
      Medicare Fee Schedule level could increase expenditures by $3.2 to $4.1 billion
      nationally; the other option would result in substantially lower increases in
      expenditures. Because of the current variations in Medicaid physician fees and in
      the breadth of eligibility across states, the cost of adopting the Medicare Fee
      Schedule varies considerably among states. CONCLUSIONS: Adopting the new Medicare
      Fee Schedule for Medicaid payments, proposed by policy-makers as a way to
      increase access to appropriate medical care, could double physician expenditures
      in some states. Adoption of more limited versions of the fee schedule might
      achieve some access gains at lower costs.

PMID- 8154556
TI  - Homicide, handguns, and the crime gun hypothesis: firearms used in fatal
      shootings of law enforcement officers, 1980 to 1989.
AB  - OBJECTIVES: Many policies seeking to limit handgun violence rest on the largely
      untested "crime gun hypothesis," which holds that subclasses of handguns differ
      in their risk for use in violent crime. This study tests that hypothesis for
      handguns used in homicides of law enforcement officers and describes the
      population of homicide-involved handguns. METHODS: A cross-sectional study was
      done of civilian (criminal) handguns used in homicides of law enforcement
      officers from 1980 to 1989. Life tables were generated for each year's cohort of
      new handguns to estimate gun-years at risk, analogous to person-years, for rate
      and relative risk calculations. RESULTS: Four hundred thirty-five deaths involved
      428 civilian handguns. Revolvers were at greater risk than pistols. For both,
      risk was lowest for .22-caliber handguns. Risk was greatest for .32-caliber
      pistols and .38-caliber revolvers. Forty-six percent of handguns had a barrel
      length of 3 in or less. CONCLUSIONS: Subclasses of handguns differ substantially
      in their risk for use in fatal shootings of law enforcement officers. Such
      epidemiological data may be useful in formulating efforts to prevent these and
      similar instances of firearm violence.

PMID- 8154557
TI  - The prevalence and correlates of fear of falling in elderly persons living in the
      community.
AB  - OBJECTIVES: Fear of falling has been recognized as a potentially debilitating
      consequence of falling in elderly persons. However, the prevalence and the
      correlates of this fear are unknown. METHODS: Prevalence of fear of falling was
      calculated from the 1-year follow-up of an age- and gender-stratified random
      sample of community-dwelling elderly persons. Cross-sectional associations of
      fear of falling with quality of life, frailty, and falling were assessed.
      RESULTS: The prevalence of fear increased with age and was greater in women.
      After adjustment for age and gender, being moderately fearful of falling was
      associated with decreased satisfaction with life, increased frailty and depressed
      mood, and recent experience with falls. Being very fearful of falling was
      associated with all of the above plus decreased mobility and social activities.
      CONCLUSIONS: Fear of falling is common in elderly persons and is associated with
      decreased quality of life, increased frailty, and recent experience with falls.

PMID- 8154558
TI  - Using physician correspondence and postcard reminders to promote mammography use.
AB  - OBJECTIVES: In a health maintenance organization that mails letters to women
      recommending that they schedule mammograms, we conducted a randomized trial to
      evaluate simple methods of increasing the use of screening mammography. METHODS:
      Using a 2 x 2 factorial design, we tested the effects of (1) mailing the
      recommendation letter from each woman's primary care physician rather than from
      the program director and (2) sending a subsequent reminder postcard. RESULTS:
      Sending a reminder postcard nearly doubled the odds that women would get
      mammograms within 1 year (participate). The letter from the woman's personal
      physician had no effect. Attending a clinic more than 45 minutes from the
      screening center, being a current smoker, or being in fair or poor health were
      negatively associated with subsequently obtaining a mammogram. The odds of
      participation doubled if women had had previous mammograms. CONCLUSIONS: When
      preceded by written recommendations to schedule mammograms, reminder postcards
      effectively increased participation. Future randomized trials to promote use of
      screening mammography should compare interventions with a reminder condition.

PMID- 8154559
TI  - The characteristics of northern black churches with community health outreach
      programs.
AB  - OBJECTIVES: The Black church has a long history of addressing unmet health and
      human service needs, yet few studies have examined characteristics of churches
      involved in health promotion. METHODS: Data obtained from a survey of 635 Black
      churches in the northern United States were examined. Univariate and multivariate
      statistical procedures identified eight characteristics associated with community
      health outreach programs: congregation size, denomination, church age, economic
      class of membership, ownership of church, number of paid clergy, presence of
      other paid staff, and education level of the minister. RESULTS: A logistic
      regression model identified church size and educational level of the minister as
      the strongest predictors of church-sponsored community health outreach. The model
      correctly classified 88% of churches that conduct outreach programs. Overall, the
      model correctly classified 76% of churches in the sample. CONCLUSIONS: Results
      may be used by public health professionals and policy makers to enlist Black
      churches as an integral component for delivery of health promotion and disease
      prevention services needed to achieve the Year 2000 health objectives for all
      Americans.

PMID- 8154560
TI  - The impact of the Safe Kids/Healthy Neighborhoods Injury Prevention Program in
      Harlem, 1988 through 1991.
AB  - OBJECTIVES: This study evaluated the effectiveness of a community coalition to
      prevent severe injuries to children in Central Harlem, New York, NY. It was
      hypothesized that injury incidence rates would decline during the intervention
      (1989 through 1991) relative to preintervention years (1983 through 1988); that
      the decline would be greatest for the targeted age group (5 through 16 years) and
      targeted injury causes (traffic accidents, assaults, firearms, outdoor falls);
      and that the decline would occur in the intervention community rather than a
      control community. METHODS: Surveillance of injuries that result in
      hospitalization and/or death among children in the two communities has been under
      way since 1983. Data from this surveillance were used to test whether the
      incidence of severe injury declined during the intervention; other temporal
      variations were controlled by Poisson regression. RESULTS: The incidence of
      injury among school-aged children in central Harlem declined during the
      intervention. The decline was specific to the targeted age group and targeted
      causes. A nonspecific decline also occurred in the control community.
      CONCLUSIONS: The declining incidence rate in Central Harlem is consistent with a
      favorable program effect, but additional investigation of possible secular trend
      or spillover effects is needed.

PMID- 8154561
TI  - Low-income neighborhoods and the risk of severe pediatric injury: a small-area
      analysis in northern Manhattan.
AB  - OBJECTIVES: The purpose of this study was to investigate the relationship between
      socioeconomic disadvantage and the incidence of severe childhood injury. METHODS:
      Small-area analysis was used to examine socioeconomic risk factors for pediatric
      injury resulting in hospitalization or death in Northern Manhattan, New York, NY,
      during a 9-year period (1983 through 1991). RESULTS: The average annual incidence
      of all causes of severe pediatric injury was 72.5 per 10,000 children; the case
      fatality rate was 2.6%. Census tract proportions of low-income households, single
      parent families, non-high school graduates, and unemployment were significant
      predictors of risk for both unintentional and intentional injury. Among the
      socioeconomic factors considered, low income was the single most important
      predictor of all injuries; other socioeconomic variables were not independent
      contributors once income was included in the model. Compared with children living
      in areas with few low-income households, children in areas with predominantly low
      income households were more than twice as likely to receive injuries from all
      causes and four and one half times as likely to receive assault injuries. The
      effect of neighborhood income disparities on injury risk persisted after race was
      controlled. CONCLUSIONS: These results illuminate the impact of socioeconomic
      disparities on child health and point to the need for injury prevention efforts
      targeting low-income neighborhoods.

PMID- 8154562
TI  - Child and adolescent drownings in Harris County, Texas, 1983 through 1990.
AB  - OBJECTIVES: This study described childhood drowning rates and circumstances in
      Harris County, a large metropolitan area in Texas, and compared case
      ascertainment between data sources. METHODS: Drowning rates among Harris County
      residents newborn through 19 years of age were calculated from death certificate
      data (1983 through 1989), and local childhood drowning hazards were described on
      the basis of medical examiner data (1983 through 1990). Cases from both sources
      were compared to determine sensitivity of sources. RESULTS: The drowning rate
      among Harris County residents newborn through 19 years of age was 3.8 per 100,000
      person-years. The drowning rates among Blacks and Hispanics exceeded that of
      Whites by 56% and 19%, respectively. The majority of the 196 unintentional
      drownings occurred in swimming pools. Half of the pool drownings occurred in
      apartment pools and 33% in private home pools. The medical examiner logbook
      identified a slightly higher number of drownings than did death certificates.
      International Classification of Diseases external cause of death codes were of
      limited use in describing drowning circumstances. CONCLUSIONS: Childhood drowning
      hazards not previously reported were identified, specifically hazards in
      apartment pools and those among Hispanic children.

PMID- 8154563
TI  - The effects of recall on estimating annual nonfatal injury rates for children and
      adolescents.
AB  - OBJECTIVES: This study used a recent national population survey on childhood and
      adolescent non-fatal injuries to investigate the effects of recall bias on
      estimating annual injury rates. Strategies to adjust for recall bias are
      recommended. METHODS: The 1988 Child Health Supplement to the National Health
      Interview Survey collected 12-month recall information on injuries that occurred
      to a national sample of 17,110 children aged 0 through 17 years. Using
      information on timing of interviews and reported injuries, estimated annual
      injury rates were calculated for 12 accumulative recall periods (from 1 to 12
      months). RESULTS: The data show significantly declining rates, from 24.4 per 100
      for a 1-month recall period to 14.7 per 100 for a 12-month recall period. The
      largest declines were found for the 0- through 4-year-old age group and for minor
      injuries. Rates of injuries that caused a school loss day, a bed day, surgery, or
      hospitalization showed higher stability throughout recall periods. CONCLUSIONS:
      Varying recall periods have profound effects on the patterns of childhood injury
      epidemiology that emerge from the data. Recall periods of between 1 and 3 months
      are recommended for use in similar survey settings.

PMID- 8154564
TI  - Characteristics of adolescent work injuries reported to the Minnesota Department
      of Labor and Industry.
AB  - OBJECTIVES: The purpose of the study was to provide descriptive data and
      incidence data on adolescent work-related injuries and to determine whether such
      injuries are underreported to the Minnesota Department of Labor and Industry.
      METHODS: The study consisted of a 1-year survey of 534 adolescent work-related
      injuries reported to the Department of Labor and Industry and a cross-sectional
      survey of 3312 public high school students from throughout Minnesota. The high
      school survey used an abbreviated questionnaire with a subset of items from the
      Department of Labor and Industry survey. RESULTS: Ninety-six percent of the
      injuries were strains and sprains, cuts and lacerations, burns, bruises and
      contusions, and fractures. There were 11 hospitalizations; 4 were for burns that
      occurred during work in restaurants. Eighty workers (15%) reported permanent
      impairment as a result of their injuries. It was estimated that there were 2268
      reportable injuries to working adolescents in Minnesota during the study year.
      CONCLUSIONS: The most common serious injuries were injuries to the lower back and
      burns. The demographic characteristics of adolescents whose injuries were
      reported to the Department of Labor and Industry were similar to those of injured
      adolescent workers identified through the high school survey. The results suggest
      that there is substantial underreporting of adolescent work injuries.

PMID- 8154566
TI  - Aggression and fighting behavior among African-American adolescents: individual
      and family factors.
AB  - OBJECTIVES: This study examined the extent to which individual and family factors
      are associated with aggression and fighting behavior among African-American
      middle school adolescents. METHODS: Four hundred thirty-six African-American boys
      and girls from two middle schools in a predominantly low-income North Carolina
      school system were surveyed and their school records examined. Information was
      collected concerning students' aggression levels, school fighting behavior,
      school suspensions for fighting, attitudes toward violence, perceptions of their
      families' attitudes toward violence, weapon-carrying behavior, and
      sociodemographics. Multivariate analyses were employed to predict the students'
      aggression levels, fighting behavior, and school suspensions. RESULTS: Factors
      related to the individual adolescents, such as gender, age, weapon-carrying
      behavior, and attitudes toward violence, were associated with students' reports
      of aggression and fighting behavior. Factors related to family and school were
      associated with school suspension for fighting. CONCLUSIONS: This study suggests
      that violence prevention programs set in our elementary and middle schools may
      reduce aggression and fighting among our youth. School teachers and public health
      practitioners are encouraged to work together in understanding and preventing
      adolescent violence.

PMID- 8154565
TI  - Factors associated with the use of violence among urban black adolescents.
AB  - OBJECTIVES: The purpose of this study was to examine social and psychological
      factors associated with the use and nonuse of violence among Black adolescents
      living in a community with a high level of violent crime. METHODS: Adolescents (n
      = 225, 44% male) 11 to 19 years of age living in or around nine housing projects
      in an urban area were administered an anonymous questionnaire. RESULTS: Self
      reported use of violence was associated with exposure to violence and personal
      victimization, hopelessness, depression, family conflict, previous corporal
      punishment, purpose in life, self-assessment of the probability of being alive at
      age 25, and age and was higher among males. CONCLUSIONS: These data support the
      hypothesis that exposure to violence is associated with adolescents' self
      reported use of violence. However, adolescents with a higher sense of purpose in
      life and less depression were better able to withstand the influence of exposure
      to violence in the home and in the community.

PMID- 8154567
TI  - Traumatic child death and documented maltreatment history, Los Angeles.
AB  - OBJECTIVES: Child abuse is a presumed but largely untested risk factor for child
      homicide. This research investigated the social and child protective service
      history of child homicide victims. METHODS: A pairwise matched case-control
      design was used to assess documented child maltreatment as a risk factor for
      homicide vs unintentional injury death. Homicide victims aged 0 to 14 years were
      identified through Los Angeles Police Department case summaries. Control subjects
      (children who died of an unintentional injury) were matched to case subjects
      (children who died from homicide) by age, sex, race/ethnicity, and date of death.
      Case and control subjects were linked with county service records to determine
      any known history of maltreatment. RESULTS: A total of 220 children were homicide
      victims during 1978 through 1987 in the city of Los Angeles. Only one in six
      children who died (of homicide or unintentional injury) or his/her family was
      known to county social or child protective services prior to the death. Recorded
      history of child protective services was associated with homicide victimization
      (adjusted odds ratio = 3.40, 95% confidence interval = 1.25, 9.27). CONCLUSIONS:
      Current service systems need assistance in identifying and protecting children at
      high risk of homicide.

PMID- 8154568
TI  - Factors that influence clinicians' assessment and management of family violence.
AB  - OBJECTIVES: High rates of family violence and low rates of detection, report, and
      therapeutic intervention by health professionals are well documented. This study
      was undertaken to determine what factors influence clinicians' decision making
      about identifying abuse and intervening with victims. METHODS: Survey data about
      clinicians' experiences with and attitudes toward family violence were gathered
      by mailed questionnaire from a random sample of practicing clinicians in six
      disciplines (n = 1521). RESULTS: Data showed similarities within and wide
      differences among three groups of subjects: dentists/dental hygienists,
      nurses/physicians, and psychologists/social workers. Overall, a third of subjects
      reported having received no educational content on child, spouse, or elder abuse
      in their professional training programs. Subjects with education on the topic
      more commonly suspected abuse in their patients than those without; among all
      subjects, spouse abuse was suspected more often than child abuse while elder
      abuse was suspected infrequently. Significant numbers of subjects did not view
      themselves as responsible for dealing with problems of family violence. Subjects
      indicated low confidence in and low compliance with mandatory reporting laws.
      CONCLUSIONS: There is a need for educators to expand curricula on family violence
      and for legislators to reexamine mandatory reporting laws.

PMID- 8154569
TI  - Suicidal ideation and attempts among chemically dependent adolescents.
AB  - OBJECTIVES: Suicidal ideation and attempts were examined in a population of
      chemically dependent adolescents, a group at high risk of self-destructive
      behavior. METHODS: The prevalence and correlates of suicidality and of major
      depressive disorder were assessed by the Diagnostic Interview Schedule and a
      structured family and social history interview with 300 addicts aged 15 through
      19 years. RESULTS: Suicidal ideation was reported by 31% to 75% of the subjects
      and suicide attempts were reported by 28% to 61%, with females predominating.
      Thoughts of suicide combined with prolonged thoughts of death in general and a
      desire to be dead were highly associated with suicide attempts. Exposure to
      physical or sexual abuse was associated with a significantly increased risk of
      suicide attempts for males but not for females. CONCLUSIONS: The probability of a
      suicide attempt increases when thoughts of suicide coincide with morbid ideation
      of extended duration, suggesting that risk assessment should be based on duration
      as well as presence of morbid thoughts. Substance abuse treatment requires an
      assessment of suicidal potential and counseling for those whose potential is
      high, with special attention to males exposed to abuse.

PMID- 8154570
TI  - The sexual assault of women at work in Washington State, 1980 to 1989.
AB  - Sexual assault in the workplace and the related factors have not been well
      studied. Workers' compensation claims data were used to describe work-related
      sexual assaults in Washington State between 1980 and 1989. Sixty-three cases of
      work-related rape were identified during this study period. The occupations of
      the rape victims were similar to occupations identified as high risk for other
      intentional injuries, and the rape incidents were characterized by isolation from
      the public and from coworkers. Estimates of industry-specific rates are
      presented. The identification, evaluation, and prevention of sexual assault and
      other workplace violence are discussed.

PMID- 8154571
TI  - Preventing occupational illness and injury: nurse practitioners as primary care
      providers.
AB  - Nurse practitioners with master's degrees were surveyed to assess the type and
      volume of occupational health services provided by primary care as compared with
      occupational health practitioners and the knowledge base in occupational health
      in these two groups. Thirty-six percent of 224 nonoccupational health nurse
      practitioners reported caseloads with 10% or more occupationally related chief
      complaints; 21% reported treating work-related injury or illness at least once
      per week. By contrast, a large percentage of nonoccupational health practitioners
      failed the knowledge-based exam. Large-scale prevention of occupational illness
      and injury warrants that primary care providers receive training in occupational
      health.

PMID- 8154572
TI  - Head injuries incurred by children and young adults during informal recreation.
AB  - To examine injuries related to playground equipment, children's vehicles, roller
      skates, and skateboards, 1991 data on emergency room patients younger than 25
      years in the Consumer Product Safety Commission's 91 surveillance hospitals were
      used. Head injury was the primary diagnosis for an estimated 58,480 patients,
      exceeding the total number of head injuries to bicyclists younger than 25 years.
      The head injury rate decreased with age. The large number and high rate of head
      injuries in children involved in a variety of recreational activities suggests
      the value of multipurpose helmets.

PMID- 8154573
TI  - A cost-benefit analysis of legislation for bicycle safety helmets in Israel.
AB  - Legislation requiring bicyclists to wear helmets in Israel will, over a helmet's
      5-year duration (assuming 85% compliancy, 83.2% helmet efficiency for morbidity,
      and 70% helmet efficiency for mortality), save approximately 57 lives and result
      in approximately 2544 fewer hospitalizations; 13,355 and 26,634 fewer emergency
      room and ambulatory visits, respectively; and 832 and 115 fewer short-term and
      long-term rehabilitation cases, respectively. Total benefits ($60.7 million) from
      reductions in health service use ($44.2 million), work absences ($7.5 million),
      and mortality ($8.9 million) would exceed program costs ($20.1 million),
      resulting in a benefit-cost ratio of 3.01:1.

PMID- 8154574
TI  - Adolescent occupational injuries requiring hospital emergency department
      treatment: a nationally representative sample.
AB  - Data from a nationally representative sample of emergency departments for the 6
      month period July through December 1992 were used to examine nonfatal
      occupational injuries sustained by adolescents aged 14 through 17 years. There
      were 679 occupational injuries, corresponding to an estimated 37,405 injuries
      nationwide. Males constituted 65.8% of the injury victims. The injury rate for
      males was 7.0 per 100 full-time employees, compared with 4.4 for females.
      Lacerations to the hand or finger accounted for 25.6% of all injuries. The
      majority of injuries occurred in retail trades (53.7%), which also had the
      highest rate (6.3 per 100 full-time employees). Seventy-one percent of the
      injuries in retail trade occurred in eating and drinking establishments.

PMID- 8154576
TI  - Reflections on a half century of injury control.
AB  - Using both historical analysis and personal reminiscence, this article describes
      the development of injury control activities since about 1940, focusing
      particular attention on the rise and fall of the Public Health Service's Division
      of Accident Prevention. By the 1940s and 1950s, modest but useful efforts in
      injury control research and programming had been made. The 1960s and early 1970s
      then saw an explosion of new concepts, programs, and enthusiasm, but much of this
      soon dissipated. Since 1985 there has been a renaissance of interest and effort,
      and the development of a new cadre of injury control professionals. This progress
      is threatened, however, by both old and new problems.

PMID- 8154575
TI  - Risk factors for violent behavior in elementary school boys: have you hugged your
      child today?
AB  - Seventeen Hispanic elementary schoolboys with violent behavior problems were
      compared with 27 matched control students who were not overtly violent at school.
      Violent boys were significantly more likely to not live with their fathers, to
      have unmarried parents, to have more siblings, and to have fathers who never show
      them affection. Parents of violent boys were more likely than those of matched
      control students to use spanking for discipline and to admit that they rarely
      express affection for their sons.

PMID- 8154577
TI  - Translating state data into local programs: targeted research for intervention
      planning (TRIP)

PMID- 8154578
TI  - The Rhode Island Sun Smart Project: skin cancer prevention reaches the beaches.

PMID- 8154579
TI  - In-line skating injuries, 1987 through 1992.

PMID- 8154580
TI  - Detecting children's passive exposure to cocaine and marijuana.

PMID- 8154581
TI  - Promoting condom availability in schools.

PMID- 8154582
TI  - Liquid chromatographic study of solute hydrogen bond basicity.
AB  - The purpose of the present work was to investigate a liquid chromatographic
      method for the measurement of relative hydrogen bond basicities of dilute
      species. This type of determination cannot be done with conventional reversed
      phase liquid chromatography due to the silanophilic interactions of basic solutes
      with the silica packing material. The studies were done on a polymeric stationary
      phase with pendant phenol groups that act as powerful hydrogen bond donors.
      Solute retention was evaluated in terms of two hydrogen bond basicity scales,
      beta 2H and beta 2C, and a steric hindrance parameter, Es. beta 2H and beta 2C
      are basicity scales based on the free energy of forming 1:1 hydrogen bond
      complexes and the retention on a strong hydrogen bond donor gas chromatographic
      phase, respectively. The Es parameter characterizes the steric effect experienced
      by the solute acceptor site. It is shown that retention correlates very strongly
      with beta 2H and less strongly with beta 2C. The log k' values need only two
      descriptive parameters, i.e., beta 2H and Es, to give a good fit. As a whole,
      retention on the phenolic polymeric phase provides an efficient method for the
      measurement of relative hydrogen bond basicities.

PMID- 8154583
TI  - Novel membraneless amperometric peroxide biosensor based on a tetrathiafulvalene
      p-tetracyanoquinodimethane electrode.
AB  - Amperometric biosensors for the detection of hydrogen peroxide are prepared by
      adsorbing peroxidase (POD, EC 1.11.1.7, lipophilized with caprylic aldehyde) to
      TTF-TCNQ/silicone oil paste electrodes. This is the first time a reductase is
      coupled to an organic conducting salt electrode. At -50 mV vs Ag/AgCl and pH 6.0,
      the current vs concentration function can be described by the enzyme kinetic
      Michaelis-Menten formalism. Stable signals are obtained within 10 s. The
      detection limit is typically in the low nanomolar range for H2O2. The enzyme
      stability under storage, standby, and various operation conditions is discussed.

PMID- 8154584
TI  - Capacitively coupled microwave plasma atomic emission spectrometer for the
      determination of lead in whole blood.
AB  - The determination of lead in whole blood by atomic emission spectrometry using a
      capacitively coupled microwave plasma and a tungsten filament electrode is
      presented. When the plasma-supporting electrode is also used as the sample
      holder, transfer of the sample to the plasma is 100%. Microwaves are used to dry
      the sample and, at higher powers, ignite a helium plasma which results in the
      atomization and excitation of Pb. Using this methodology, a detection limit of 3
      pg of Pb was obtained using 5-microL aqueous samples. The precision was 9%. Whole
      blood samples were subjected to a drying stage similar to that of the aqueous
      samples. Following this drying stage, a low-power (30 W) helium plasma was
      ignited and used to ash the blood sample. Higher power plasmas (> 150 W) were
      used to atomize and excite the Pb. Recovery of Pb from the blood samples was 88%,
      when compared to aqueous standards.

PMID- 8154585
TI  - Activated carbon paste electrodes for biosensors.
AB  - A reagentless amperometric glucose biosensor was constructed using glucose
      oxidase and hydroquinone (H2Q) coimmobilized in carbon paste. The sensor response
      was studied by amperometry and cyclic voltammetry in quiescent solutions, as well
      as in a flow injection apparatus. Studies were conducted as a function of surface
      activation and sensor working conditions such as glucose concentration, storage,
      aging, and reusability. Surface activation proved to be useful to improve the
      electro-chemical reversibility of the mediator and the analytical characteristics
      of the sensor. The harsh conditions of the surface pretreatment did not
      deactivate the enzyme. Results from the assay of a clinical sample gave a glucose
      concentration value of 76 +/- 6 mg/dL, which compared favorably with the expected
      range of 72-88 mg/dL.

PMID- 8154586
TI  - Simplified dual-lumen catheter design for simultaneous potentiometric monitoring
      of carbon dioxide and pH.
AB  - A novel dual-lumen catheter electrode design suitable for the simultaneous
      measurement of PCO2 (partial pressure of carbon dioxide) and pH in flowing blood
      is described. The probe is fabricated from a single segment of dual-lumen
      silicone rubber or polyurethane tubing that is impregnated with the proton
      ionophore tridodecylamine. The impregnation step imparts H+ permselectivity to
      both inner and outer walls of the tubing. By filling each lumen with a suitable
      buffer/electrolyte solution and Ag/AgCl reference electrode wire, simultaneous
      potentiometric detection of both PCO2 and pH is achieved. Careful optimization of
      incorporated proton carrier (tridodecylamine), plasticizer (o-nitrophenyl octyl
      ether), and lipophilic counteranion sites (tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate) within the tubing walls yields catheter
      electrodes with resistance values of 10-20 M omega and relatively high stability
      in flowing blood. Results from continuous measurements of PCO2 and pH during long
      term 30-65-h blood loop experiments demonstrate that, after an initial
      conditioning period, the catheter exhibits low drift rates (PCO2, 4.7 +/- 1.7
      mV/30 h; pH, 1.4 +/- 0.5 mV/30 h) and yields continuously measured values in good
      agreement with those obtained on discrete samples with a commercial blood gas
      analyzer (PCO2, r2 = 0.997; pH, r2 = 0.915). In vivo evaluation of the catheter
      sensors, performed by implanting silicone rubber dual-lumen probes in the
      arteries of anesthetized dogs, indicates that the proposed catheter design can
      closely follow PCO2/pH changes induced in the animals during 6-13 h of continuous
      monitoring.

PMID- 8154587
TI  - Characterization of humanized anti-TAC, an antibody directed against the
      interleukin 2 receptor, using electrospray ionization mass spectrometry by direct
      infusion, LC/MS, and MS/MS.
AB  - Characterization of a humanized monoclonal antibody (Hu-anti-TAC) directed
      against a surface protein expressed on T-lymphocytes was performed with an
      electrospray mass spectrometer. Capillary reversed-phase liquid chromatography
      (LC)/mass spectrometry (MS) and direct infusion MS were utilized along with
      tandem MS/MS analysis to confirm the sequence and to determine the sources of
      heterogeneity in Hu-anti-TAC. The MS analysis was performed on disulfide-reduced
      and trypsin-digested samples of the antibody. Two forms of diantennary
      carbohydrate structures were identified and found to be consistent with those
      reported for the human IgG1 framework. The analysis demonstrated that the N
      terminus was modified by conversion of a glutamine residue to pyroglutamic acid.
      Another source of heterogeneity was the partial removal of the C-terminal lysine
      residue and was confirmed by mass calculations of tryptic peptides followed by
      MS/MS sequencing. This study demonstrates that the high sensitivity of
      electrospray mass spectrometry when combined with capillary chromatography can
      allow detailed characterization of microgram samples of high molecular weight
      proteins such as antibodies.

PMID- 8154588
TI  - On-line coupling of in vivo microdialysis sampling with capillary
      electrophoresis.
AB  - Microdialysis sampling has become an important means of continuously monitoring
      reactions in vivo. This sampling technique places a constraint on the analysis
      method because of the very small sample volume provided. On the other hand,
      microdialysis provides the advantage of clean samples that do not require cleanup
      prior to analysis. An on-line coupling of microdialysis sampling to capillary
      electrophoretic (CE) analysis is described that uses the advantages of
      microcolumn separations to overcome the small volume limitation. An interface was
      designed which converts the continuous microdialysis sample stream into discrete
      60-nL sample plugs and then injects a portion of this plug into the CE system.
      The on-line interface provided precision of 2.6% with minimal band broadening or
      peak height loss relative to off-line sampling. Using a high-speed micellar
      electrokinetic chromatography (MEKC) separation, resolution of the
      investigational antineoplastic SR 4233 from its main metabolite SR 4317 was
      achieved in less than 60 s. This allowed the on-line system to achieve a 90-s
      temporal resolution for determining the pharmacokinetics of SR 4233 in vivo.

PMID- 8154589
TI  - Prevention of the rapid degradation of subcutaneously implanted Ag/AgCl reference
      electrodes using polymer coatings.
AB  - To assess the effect of the biological response to implanted Ag/AgCl reference
      electrodes on the electrode stability, uncoated and polymer-coated Ag/AgCl
      electrodes were implanted subcutaneously in rats. After 1 week of implantation,
      uncoated Ag/AgCl electrode potentials, measured in 0.1 M KCl, shifted by about 
      180 mV, and both voltammetry and electron microscopy showed that all the AgCl was
      removed. The electrodes could be significantly protected by coating with
      polyurethane or a perfluorinated ionomer (Nafion) cured at 120 degrees C for 1 h.
      Electron micrographs showed the 120 degrees C cured Nafion and polyurethane
      coatings remained intact over 2 weeks of implantation. Following 2 weeks of
      implantation the cured, Nafion-coated electrodes' potentials were shifted by -15
      +/- 7 mV relative to the initial values. Voltammetry showed that they were still
      not polarizable. The current densities obtained with the coated reference
      electrodes are sufficient for their use as counter/pseudoreference electrodes
      with implantable two-electrode glucose sensor systems. The tissue response to
      coated electrodes was minimal in comparison to the response to uncoated reference
      electrodes.

PMID- 8154590
TI  - Effects of cations and charge types on the metastable decay rates of
      oligosaccharides.
AB  - Metastable decay rates of alpha-cyclodextrin and maltohexaose coordinated to
      proton and alkali metal ions were determined from ions produced by liquid
      secondary ion mass spectrometry in an external source Fourier transform mass
      spectrometry instrument. For both oligosaccharide compounds the decay rates of
      the protonated species are faster than any alkali metal coordinated species.
      Decay rates of the metal cationized species decrease in the order Li+, Na+, K+,
      and Cs+. The anion of alpha-cyclodextrin has the slowest measurable decomposition
      rate. The relationships between cation affinities and rates are explored.

PMID- 8154591
TI  - Conformation of cytochrome c studied by deuterium exchange-electrospray
      ionization mass spectrometry.
AB  - Deuterium exchange of bovine cytochrome c has been monitored by electrospray
      ionization mass spectrometry. Different charge-state distributions in the mass
      spectrum appear to represent different protein conformations, but rapid
      interconversion of the conformations can lead to a coincidence of the deuterium
      exchange rates. When interconversion is blocked, the conformation corresponding
      to higher m/z (lower charge) exchanges more slowly, indicating a tightly folded
      state. Furthermore, the data suggest that at least two conformations can have
      identical charge-state distributions, but have different exchange rates. Thus,
      neither charge-state distribution nor deuterium exchange rate alone is a
      sufficient indicator of protein conformation.

PMID- 8154592
TI  - Capillary gas chromatographic introduction of environmental compounds into a
      trochoidal electron monochromator/mass spectrometer.
AB  - A gas chromatograph was interfaced to an electron monochromator/quadrupole mass
      spectrometer. The new system was tested for the analysis of environmental
      compounds. Detection sensitivity for hexachlorobenzene (HCB) through the gas
      chromatograph was 5 pg or better, and a mass-resolved molecular ion cluster for
      this compound on the fly was achieved with 10.8 ng of sample. An ion chromatogram
      was obtained using 45 ng of Aroclor 1254, and the extract from a trout muscle
      sample recently collected in the Arctic yielded a chromatographic profile similar
      to that observed using negative ion chemical ionization mass spectrometry. A
      mixture of HCB and 2,4,6-trinitrotoluene (TNT) were shown to be distinguishable
      at 2.4-eV electron energy. The energetics of regioselective fragmentation of [4
      15NO2]TNT by dissociative electron capture can be determined on the fly. Complete
      negative ion gas chromatography/mass spectrometry (GC/MS) spectra were obtained
      for hexafluorobenzene and TNT by simultaneously ramping the electron energy from 
      2 to 15 eV and scanning the mass over a 200-Da range.

PMID- 8154593
TI  - Simultaneous separation of inorganic cations and anions by ion chromatography
      using a single column coated with weak/strong-charged zwitterionic bile salt
      micelles.
AB  - A single reversed-phase ODS (octadecyl silica) column coated with taurine
      conjugated bile salt micelles has been investigated for simultaneous separation
      of inorganic cations and anions. Under acidic conditions in the separation
      column, taurine-conjugated bile salts are protonated; therefore, the stationary
      phase coated with taurine-conjugated bile micelles exists as a "weak/strong"
      charged zwitterionic stationary phase (H+ and SO3-). The weak/strong-charged
      zwitterionic stationary phase provides a new retention mechanism which is
      different from conventional ion chromatography in that both positive and negative
      charges are close together in a single molecule, resulting in simultaneous
      electrostatic attraction and repulsion of the analyte ions. Also, the stronger
      negative charge (sulfonate) of the stationary phase works as a cation-exchange
      site at the same time. The combined effects of cation-exchange and simultaneous
      electrostatic repulsion/attraction interactions were successfully used in ion
      chromatography for the simultaneous separation of inorganic cations and anions.

PMID- 8154594
TI  - Measurement of coarse aerosols in workplaces. A review.
AB  - Coarse aerosol fractions in workplaces are sampled if it is felt that particles
      of all sizes may pose a risk to health. Although the so-called 'total' aerosol
      has been widely used to refer to the relevant coarse fraction, practical
      measurement has been very dependent on the actual sampling instrument used. This
      in turn has led to great uncertainty about what was being measured. In the 1980s,
      the concept of inhalability was proposed, based on the aerosol particle size
      fraction that enters the human head through the nose and/or mouth during
      breathing. Now there is substantial agreement by most of the world's major
      criteria-setting bodies on a quantitative definition taking the form of a single
      curve describing the probability of inhalation as a function of particle
      aerodynamic diameter. This definition now forms a truly health-related
      'yardstick' against which to assess the performances of practical sampling
      devices. In turn, more and more countries are beginning to adopt the new
      criterion for health-related aerosol measurement in their standards, replacing
      the old 'total' aerosol concept. Experiments in wind tunnels to investigate the
      performances of previous samplers for 'total' aerosol show that most of them do
      not satisfactorily match the new inhalability criterion. A small number of
      samplers designed specifically for the inhalable fraction have been proposed and
      are available commercially. They include samplers for both static (or area) and
      personal sampling.

PMID- 8154595
TI  - Inductively coupled plasma atomic emission spectrometric determination of
      aluminium, barium, silicon, strontium and titanium in food after sample fusion.
AB  - A rapid and accurate method for the inductively coupled plasma atomic emission
      spectrometric determination of Al, Ba, Si, Sr and Ti in food was developed based
      on a direct lithium metaborate fusion without sample pre-ashing. Six NIST diet
      test samples were analysed. Three independent sample preparation procedures were
      compared for verification.

PMID- 8154597
TI  - Measuring strategies for the nineties. Future needs from the health point of
      view.
AB  - Technological progress and related social processes will determine the measuring
      strategies of workplace air monitoring for the nineties even if the objective is
      dose estimation or compliance. Expectations of the lowest possible exposure,
      require workplace air monitoring to be closely linked to process control in a
      life cycle approach. Production regularity and preventive maintenance also become
      important factors for strategy design. Workroom air may lose some importance as a
      dose estimate for the estimation of toxicological risk, as multi-factorial causes
      for work-related diseases become more evident and a number of syndromes of
      unknown aetiology become increasingly important. Cancer, cardiovascular diseases,
      the indoor air syndrome and multiple chemical sensitivity are given as examples.
      Biotechnology and the information revolution have changed the basic principles of
      health monitoring and surveillance. The individual worker becomes the target and
      the possibility of individually adjusted monitoring, surveillance and workplace
      design becomes important.

PMID- 8154596
TI  - Measurement of fine aerosols in workplaces. A review.
AB  - The fine aerosol fractions of interest in occupational health are those
      associated with the regional deposition of inhaled aerosols in the different
      parts of the human respiratory tract. The recent recommendations of the
      International Standards Organization, the American Conference of Governmental
      Industrial Hygienists and the Comite Europeen de Normalisation define the
      thoracic fraction (inhaled particles which penetrate into the lung) and the
      respirable fraction (inhaled particles which penetrate further into the alveolar
      region). Based on the results of inhalation experiments with humans, conventional
      curves for these fractions are proposed, which provide 'yardsticks' for health
      related sampling devices. Samplers for the respirable fraction have been in
      existence since the early 1950s, and a fairly large range of acceptable
      instrumentation is available commercially. Recently, however, attention has been
      drawn to the effect of even small departures from the 'target' curve on the
      respirable mass sampled. This suggests the need for additional criteria for
      sampler acceptability, based on sampled mass in addition to particle size
      selectivity. Samplers for the thoracic fraction may be based on similar physical
      concepts to those for respirable aerosol. In addition, versatile devices capable
      of providing information about more than one fraction simultaneously are being
      proposed and are finding increasing use as investigative tools for industrial
      hygienists. Finally, measurement of fine fibrous aerosols is recognized as a
      special case, and so is treated separately.

PMID- 8154598
TI  - Direct-reading instruments for aerosols. A review.
AB  - Direct-reading instruments for aerosols have not had the popularity within the
      industrial hygiene community that similar instruments for gases and vapours have
      enjoyed. There are several reasons for this: aerosols have complex properties
      that are difficult to characterize with a single measurement, commercial
      instruments often do not provide an accurate measure of a useful aerosol property
      and aerosol instruments are relatively expensive for industrial hygiene use. A
      variety of instruments are commercially available and are briefly reviewed. Two
      general classes of instruments used for industrial hygiene measurements are
      covered: field instruments and research instruments. The International Symposium
      on Air Sampling Instrument Performance held in Research Triangle Park, NC, USA,
      in October, 1991 included a workshop on direct-reading aerosol instruments that
      produced several recommendations to advance the state of the art. The two primary
      recommendations approved by the symposium attendees were to develop voluntary
      consensus standards for aerosol mass measuring instruments and optical particle
      counters and to develop an accurate, portable, direct-reading aerosol mass
      monitor. Some progress is being made on the latter recommendation through a
      project supported by the US Bureau of Mines. Other instruments have found
      specific application in industrial hygiene measurements. A miniaturized
      condensation nucleus counter is being used to estimate fit factors for
      respirators. A fibre monitor is used for monitoring asbestos, especially in
      asbestos abatement operations. Optical particle counters are used for low
      concentration aerosols, especially in clean rooms. Aerosol research instruments
      are being used to evaluate and improve field instrumentation, such as respirable,
      thoracic and inhalable samplers and cascade impactors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8154599
TI  - Sampling of biological particles.
AB  - Sampling strategy, sampling and analysis of different biological particles,
      mainly fungal spores and bacteria, are reviewed. The sampling is strongly
      dependent on the environment, time of year and activity at the workplace. The
      choice of suitable sampling equipment depends on the levels of airborne micro
      organisms. For sampling in non-industrial indoor environments (< 10(6) micro
      organisms m-3), slit samplers, cascade impactors and multistage impingers can be
      used. At high concentrations of airborne micro-organisms (> 10(6) micro-organisms
      m-3), other types of methods must be used because the slit samplers and cascade
      impactors, such as Andersen samplers, are often overloaded. Sampling using
      polycarbonate filters is one method that can be used. Other useful methods are,
      for example, multistage liquid impingers or an Aerojet General Glass Cyclone.
      Analysis of the filter by cultivation gives lower values than microscopy. Direct
      analysis of the filter by scanning electron microscopy results in values that are
      2-3 times higher than those obtained by analysis using Acridine Orange staining
      and epifluorescence microscopy. Suspension of biological particles in liquid
      before microscopic analysis results in the observation of more single spores,
      which suggests that large spore aggregates break down during suspension.

PMID- 8154600
TI  - Strategies for the simultaneous collection of vapours and aerosols with emphasis
      on isocyanate sampling.
AB  - Workplace air frequently contains hazardous substances that may be present as
      vapours or as aerosols with a wide range of particle sizes. Depending upon a
      chemical species' volatility and use, it may be present in significant amounts in
      both the vapour and particulate phases. Unfortunately, the mechanisms by which
      vapours and particles are removed from an air stream during pumped sampling are
      substantially different. Collection of vapour molecules relies on their diffusion
      to a surface during their residence time in a sampler. Once in contact with a
      surface, vapour molecules are trapped either by adsorption onto a solid surface,
      absorption by a liquid, or by reaction with the medium or chemicals in the
      medium. Aerosol particles are most frequently collected by filtration or inertial
      impaction. However, if it is necessary to collect both phases simultaneously, a
      sampler with two stages is generally required. The exact nature of the sampler
      depends upon the size of the aerosol particles and the physical and chemical
      characteristics of the species of interest. A number of recent projects
      undertaken by researchers at the National Institute for Occupational Safety and
      Health have dealt with development of sampling and analytical methods for
      compounds present in workplace air as both vapour and aerosol particles. One
      strategy invoked in several instances consisted of a filter for particle
      collection followed by an appropriate second stage for vapour collection. For
      organophosphorus pesticides, the second stage was a sorbent tube. For gaseous
      hydrogen fluoride, it was an alkaline-impregnated back-up pad. For formaldehyde,
      the second stage was an impinger containing an aqueous solution of sodium
      hydrogensulfite.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154601
TI  - European standardization: guidance on the assessment of occupational exposure to
      chemical agents. CEN TC 137.
AB  - Working group 1 of CEN TC 137 has produced a draft proposal for the assessment of
      exposure to chemical agents and measurement strategy. A review of the standard is
      given. The purpose is to give practical guidance to those who have to carry out
      these assessments. A systematic approach allows the number of measurements to be
      reduced. The report of the work done allows communication in an efficient way
      with interested parties: workers, occupational physicians and the labour
      inspectorate.

PMID- 8154602
TI  - Stereological analysis of collagen and elastic fibers in the normal human dermis:
      variability with age, sex, and body region.
AB  - Normal human dermis has been analyzed using stereological methods to estimate the
      quantitative modifications of collagen and elastic fibers in relation to age,
      sex, and body region. Forty-five skin biopsies from the trunk or the limbs of 26
      males and 19 females of different age were fixed in glutaraldehyde and osmium
      tetroxide and embedded in epoxy resin. The relative volumes of collagen and
      elastic fibers were calculated by the point counting method on 1 micron semithin
      sections. Photographic sampling was performed on four consecutive dermis layers:
      the papillary layer and three consecutive layers of reticular dermis. The data
      were subjected to analysis of variance which showed that all the factors studied
      exert a significant influence on the relative amounts of collagen and elastic
      fibers. The fractional volume of collagen fibers is constant throughout all
      dermis layers analyzed and is always higher in females than in males, except for
      the second and third decades of life. Collagen fiber density increases with age
      in both sexes up to 30-40 years, when it starts decreasing. Both the relative
      volumes and the diameters of elastic fibers increase from papillary to deep
      reticular dermis. In reticular dermis of both sexes there is an increment of
      elastic fiber density in the first decade of life, followed by a drop
      particularly marked in males. After 20 years, the relative volume of elastic
      fibers displays a decreasing trend in females, whereas it increases in males,
      attaining the highest values beyond the 40s.

PMID- 8154603
TI  - Ultrastructure as a basis for dating of rat endometrium.
AB  - Studies on the endometrial cycle depend upon the precise dating of the cycle
      stage. In the present paper the generally applied method of vaginal smear was
      carefully verified through the measurement of the hormones relevant to the
      endometrial cycle. From rats predated through vaginal smear cytology, the hormone
      levels of estradiol-17-beta (E2) and progesterone (P), luteinizing hormone (LH),
      and follicle stimulating hormone (FSH) were measured. The values obtained were
      then compared to the standardized values of our reference curve. Animals with
      values that did not fit within the standard deviation of our reference curve were
      excluded from this investigation. Thus, for the first time exactly dated rat
      endometrial morphology was studied with electron microscopy. The morphology of
      the surface epithelium of rat endometrium from all four stages of the cycle is
      described in detail. In addition a semiquantitative morphometric analysis of the
      following parameters was performed: cell volume, nuclear volume, the volume
      density of secretory granules, digestive vacuoles, mitochondria, Golgi apparatus,
      rough endoplasmic reticulum, and lipid vacuoles as well as the size of lipid
      vacuoles. With the cellular content of lipid vacuoles and their diameter, it is
      possible to differentiate between proestrus/estrus and diestrus I/diestrus II,
      the latter possessing definitely more and larger lipid vacuoles. During estrus
      the greatest cytoplasmic volume develops. In addition to this, secretory granules
      are only present during estrus. Finally, diestrus I can be well differentiated
      from diestrus II, because diestrus I exhibits more digestive vacuoles and during
      diestrus II a high percentage of free ribosomes is present. On the basis of
      distinct morphological features, described in this paper, it is now clearly
      possible to distinguish between the four different cycle stages.

PMID- 8154604
TI  - Initial vascularisation in the pig placenta: I. Demonstration of nonglandular
      areas by histology and corrosion casts.
AB  - The vascular interrelationship of the well-established porcine placenta has
      previously been described from vascular casts and histology, but not its
      developmental stages. This study was performed using the same methods on 17 sows
      of well-known stages of gestation ranging from 9 1/2 to 43 days post coitum
      (p.c.). At the precontact stage, days 9 1/2 to 12 1/2 p.c., the subepithelial
      capillaries formed a wide open meshwork of variable diameter, 3-14 microns,
      without any difference between meso- and antimesometrial side. At the early
      contact and adhesion stages (days 13 to 18 p.c.), the first increase in
      vasculature was seen at the mesometrial side close to the embryonic disc of the
      very long blastocyst at day 15 p.c., 2 days after the first contact between
      trophoblast and maternal epithelium was seen. At day 18 p.c., the areas with
      dense capillaries increased markedly at the mesometrial side with the same
      parallel organization as seen at day 15 p.c., whereas the antimesometrial side
      still had a relative loose appearance comparable to the previous stages. At the
      early placental stages (days 20 1/2 to 23 p.c.), the capillary bed formed smooth
      folds, which in some areas at day 20 1/2 days developed into smaller folds or
      prerugae. Here the capillaries changed to convoluted forms with slightly bulbous
      dilations measuring about 30-35 microns in diameter. This developmental progress
      became more elaborate at day 23: capillaries of the low ridges of prerugae formed
      irregular dilations up to 50 microns in some areas. At this stage the parallel
      arrangement of the capillary meshwork characteristic of the previous stage was
      not longer discernable. By days 32-43 p.c., an increase in microscopic folding
      was present, and the maternal arterioles could be traced to the top of the
      ridges, creating the characteristic vascular architecture needed for an efficient
      exchange of oxygen, carbon dioxide, and nutrients of the basically developed
      porcine placenta.

PMID- 8154605
TI  - Postnatal differentiation and development of the rat epididymis: a stereological
      study.
AB  - Postnatal development and differentiation of the rat epididymis was studied in
      the rat from 15 to 120 days of life using stereological techniques. Both the
      relative volume (volume density) and absolute volume of the epithelial,
      interstitial, and luminal compartments in the initial segment, caput, corpus, and
      cauda epididymides were determined. In all segments the volume density of the
      epithelial compartment increased between days 15 and 30 before falling to adult
      values at 45 days in the initial segment (0.476 +/- 0.031), at 60 days in the
      caput (0.258 +/- 0.028) and at 90 days in the corpus (0.245 +/- 0.007) and cauda
      (0.140 +/- 0.004). The relative volume of the interstitium decreased, whilst that
      of the lumen increased over the same period with adult values being achieved
      earlier in the proximal segments than in the distal segments. In contrast to
      volume fraction the absolute volume of all compartments in all segments increased
      from day 15 to day 90. Between 90 and 120 days the absolute volumes of
      compartments in the initial segment and caput showed little volume change. All
      compartments in the corpus and cauda showed significant increases in volume over
      the same period. A similar pattern of development was observed with respect to
      the surface area of both the luminal and basement membrane aspects of the
      epithelium; surface area per unit volume (surface density) in all segments
      reached adult values at approximately 60 days, whilst the increase in absolute
      area of the surfaces ceased at 90 days in the initial segment and caput and
      continued to 120 days in the corpus and cauda.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154606
TI  - Quantitative study on the relation between structural and functional properties
      of the hearts from three different mammals.
AB  - The ultrastructural quantitative composition of left ventricular cardiac myocytes
      from isolated Langendorff-perfused hearts was studied in three different mammals
      (rabbit, guinea pig, and rat). Volume densities of mitochondria, myofibrils, and
      unspecified cytoplasm were determined using morphometry and were compared to
      functional parameters including left ventricular developed pressure (LVDP),
      contractility (dP/dt), heart rate, TTI (tension-time index, an index of oxygen
      consumption), and relative heart mass (H/B) obtained from these hearts. Each of
      the mammals was found to possess a very specific and characteristic quantitative
      composition of cardiac myocyte. Cardiac myocytes contained 26.8% mitochondria and
      56.3% myofibrils in rabbits, 25.8% mitochondria and 60.9% myofibrils in guinea
      pigs, and 27.7% mitochondria and 58.1% myofibrils in rats. The LVDP,
      contractility, heart rate, and TTI were quite different among species. However,
      there were close correlations between the mitochondrial volume density and the
      LVDP (p < 0.05), and between the mitochondrial volume density and the TTI (p <
      0.05), in any group of the animals. It is concluded that the mitochondrial volume
      density is a good indirect indicator of function of cardiac muscle related to
      oxidative capacity.

PMID- 8154607
TI  - Plasticity of innervation of the medulla of axillary lymph nodes in the rat after
      antigenic stimulation.
AB  - The purpose of this investigation was to test the hypothesis that activation of
      the immune system in rats will lead to changes in the density of innervation in
      lymph nodes. In order to reduce the variability between animals, the rats were
      reared under sterile conditions and immunostimulation was effected by
      subcutaneous application of bovine albumin in a region draining to the axillary
      lymph nodes of both sides. Control animals received an equivalent application of
      sterile physiological saline. The animals were sacrificed 10 days and 27 days and
      4 months after immunostimulation. The nerves in the axillary lymph nodes were
      quantified by light microscopy in silver impregnated sections and at the
      ultrastructural level on ultrathin sections. The survival times were chosen so
      that the first group was in the ascending phase of antibody production, the
      second group at the peak, and the third group in the declining phase. Both at the
      light and ultrastructural levels, there were statistically significant
      differences in the density of innervation of medulla between the groups, with a
      particularly pronounced increase in the group 4 months after immunostimulation.
      At the ultrastructural level, there was also an increase in the density of
      incompletely ensheathed axonal profiles in the parenchyma of the medulla, while
      the nerves associated with blood vessels were not increased. We conclude that
      immunostimulation leads to morphological changes in the innervation of the
      medulla of axillary lymph nodes, that are consistent with the concept of
      functional activation of the autonomic nervous system through the immune system.

PMID- 8154608
TI  - Domains of differential cell proliferation and formation of amnion folds in chick
      embryo ectoderm.
AB  - Patterns of cell proliferation in ectoderm epithelium that will form avian amnion
      correlate with morphogenesis, but not in an obvious pattern with respect to large
      scale folding. At sites where the pre-axial amnion folds will first appear in 4-
      to 8-somite embryos, patterns of proliferation do not separate into domains that
      presage location of the single pre-axial fold that is commonly described in
      embryology texts. Instead, increased cell proliferation occurs in a significant,
      bilateral pattern. In stages with 13 to 27 somites, when lateral amnionic folds
      are prominent, five paraxial domains of cell proliferation correlate with
      morphology and show decreasing levels of cell proliferation with distance from
      the neural axis. Slowly growing areas surround rapidly growing areas and could
      assist buckling of epithelium by providing constraints on expansion of faster
      growing areas. Proliferation domains in ectoderm correlate with morphology and
      morphological events when localized changes in cell shape are lacking and suggest
      a role for differential cell proliferation in formation of large-scale epithelial
      folds in early chick embryos.

PMID- 8154609
TI  - Septation of the respiratory and digestive tracts in human embryos: crucial role
      of the tracheoesophageal sulcus.
AB  - Esophageal atresia and tracheoesophageal fistula, common malformations of the
      respiratory and digestive tracts, are of unsettled pathogenesis. Part of the
      difficulty in understanding these abnormalities arises from the uncertainties
      about the normal developmental processes in the region. This study examined the
      development and fate of the tracheoesophageal septum. Normal human embryos from
      the Carnegie Embryological Collection and fetuses from the Hopkins Pathology
      Collection were examined, and reconstructions of selected specimens were made
      from photomicrographs of serial histologic sections. The results show that the
      lung bud appears in Carnegie stage 12, rapidly enlarges, and bends caudally,
      thereby producing a sulcus between the foregut and the respiratory system on its
      caudal aspect. The cranial aspect of this tracheoesophageal sulcus remains fixed
      at the levels of the first cervical vertebra throughout subsequent embryonic and
      fetal development. At the same time the trachea and esophagus elongate to bring
      those part of the respiratory and digestive systems into their definitive
      anatomic positions. Examination of the tracheoesophageal sulcus shows that its
      growth-limiting properties may be explained by its catenoidal configuration.
      Catenoidal, or saddle-shape, sulci have been shown to have similar regional
      growth-limiting properties in the embryonic heart. These regions contrast with
      outwardly convex regions in both the developing heart and lung where growth of
      the tissues occurs. The observations made here suggest that the origin of the
      tracheoesophageal malformations must be sought in a configurational abnormality
      in the area of the developing lung bud in Carnegie stage 12.

PMID- 8154610
TI  - Effects of peripheral axotomy on presynaptic axon terminals with GABA-like
      immunoreactivity.
AB  - The facial nerve was unilaterally crushed at its exit from the stylomastoid
      foramen in three 3-month old male rats. After 10 days survival, before the
      regenerating axons had reinnervated their target muscles, the facial nucleus was
      examined to determine central patterns of response in material prepared to
      demonstrate the presence of GABA-like immunoreactivity with postembedding
      procedures using gold-labeled secondary antibody. The uninjured nucleus served as
      a control. In both control and injured nuclei, the GABAergic terminals synapse
      with all parts of the motor neurons, except the axon, and exhibit diverse
      morphologies. GABAergic axon terminals vary in their size and in the electron
      density of their axoplasm and the majority of the terminals contain pleomorphic
      vesicle profiles that display a range in their packing density and size. In both
      control and injured facial nuclei, only approximately 40% of the axon terminal
      profiles with pleomorphic vesicles exhibit GABA immunoreactivity. A morphometric
      analysis of the synaptic vesicle profiles in the GABA-positive terminals reveals
      that following axotomy there is no change in the mean number of synaptic vesicle
      profiles per GABAergic terminal profile. However, the mean size of the synaptic
      vesicle profiles in these terminals shows an axotomy-induced 50% increase,
      without change in the shapes of the enlarged vesicle profiles. Also, the
      numerical density of gold particles associated with the GABA-positive terminals
      is consistently greater in the injured than the control axon terminals. In the
      control animals quantitative analysis of the relative distribution of all axon
      terminal profiles in the neuropil categorized by the shape of their vesicle
      profiles as round, pleomorphic, or flat is 57:37:6. Ten days after axotomy the
      ratio of these categories in the injured nucleus has shifted to 35:60:5. This
      study demonstrates that the functional state of a postsynaptic target can
      influence the morphology of vesicle profiles in presynaptic elements as well as
      patterns of its afferent input.

PMID- 8154611
TI  - Tongue structure and function in Oplurus cuvieri (Reptilia: Iguanidae).
AB  - The anatomy of the hyo-lingual apparatus in the iguanid lizard Oplurus cuvieri
      has been studied by light microscopy and scanning electron microscopy. Four areas
      were observed on the dorsal lingual epithelium of the lizard. Tongue tips are
      covered with a smooth epithelium. Closely packed flattened and cylindriform
      papillae cover the foretongue. The surface of the midtongue bears an unpapillose
      epithelium. Short conical papillae are arranged on the two lateral posterior
      bundles of the tongue. At high magnification, microvilli and microridges are
      widely distributed over the surface of the papillae. The epithelium of the
      papillae is composed of cells filled with secretory granules. Each surface plays
      successive roles during food ingestion, intra-buccal transport, and swallowing.
      The mucous interpapillary spaces would serve the adherence between the tongue and
      the food, the smooth epithelium of the midtongue should facilitate movements of
      the prey toward the pharynx, and conical papillae of the hindtongue present a
      rough surface which should act on the prey during the swallowing phase. The
      intrinsic morphology of the tongue is rather similar to that previously described
      for iguanids, but fibers of M. verticalis encircles ventrally the lingual
      process. These fibers could act in tongue protrusion as previously suggested for
      agamids. The morphology and function of the extrinsic tongue musculature and the
      hyoid musculature, analysed by electrical stimulations, are similar to the
      previous descriptions in iguanids and agamids either for feeding or displaying
      functions.

PMID- 8154612
TI  - High field magnetic resonance imaging of normal and pathologic human medulla
      oblongata.
AB  - High field proton magnetic resonance (MR) imaging has been applied to depict the
      MR appearance of the normal excised human cervicomedullary junction, based on
      which neuropathologic specimens can be described. More specifically, two normal
      cases and one case of Chiari deformity were imaged in the transverse, sagittal,
      and coronal dimensions using a 9.4 Tesla vertical bore magnet. The MR images of
      the normal specimens reveal most of the neuroanatomical microstructures described
      in literature. An accurate description of the Chiari deformity could be made by
      comparing the MR reference images with those of the pathologic specimen. All MR
      detected abnormalities were confirmed by histopathology, by which no additional
      lesions could be found.

PMID- 8154613
TI  - [Analysis of microsporum dermatomycoses in Szczecin, its terrain and regions in
      the years 1985-1988].
AB  - The retrospective analysis of M. canis infections in Szczecin and its region, and
      the comparison with other dermatomycoses are presented. The study comprised two
      groups of patients: 450 patients diagnosed between January 1985--December 1988 to
      have microsporum infections, and 449 patients with the diagnosis of
      dermatomycosis made between January 1986--December 1988. Data collected in form
      of patients personal cards were subsequently analysed with the use of standard
      statistical methods. Most of cases of M. canis infections occurred in females
      younger than 14 years, while the preponderance of adult males was observed among
      patients with other dermatomycoses. In patients with microsporum infections, skin
      lesions were most commonly located on the face, limbs and chest as well as on the
      scalp in children. In patients with other dermatomycoses, skin lesions were
      placed on feet, inter-hallux spaces and toe nails. Infected animals, especially
      stray cats, less frequently dogs, played an important role in the spread of
      microsporum infections. The disease was characterized by the seasonal pattern
      with the peak incidence between August and December. The rising number of
      microsporum infection with clinical picture and animal sources of infection,
      distinctive from other dermatomycoses, is currently observed in Szczecin and its
      region.

PMID- 8154614
TI  - [Late consequences of cranio-cerebral traumas in light of clinical, psychologic
      and computerized tomography examinations].
AB  - The paper presents remote consequences of cranio-cerebral traumas in a selected
      group of 62 patients with a varying degree of severity. Neurological,
      psychological consequences as well as changes in morphology of brain tissues have
      been taken into consideration. The aim of the paper was to evaluate the
      neurologic--psychological state, and to perform analyses covering the
      morphological changes of encephalon in remote (3 months--3 years) period after
      the cranio-cerebral trauma, and also to study the interdependences between the
      severity of injury on the one hand, and the clinical--psychological status as CT
      scan of the head in the late period, on the other. Disability features ware
      disclosed in a total of 39% of the examined subjects. Diminution of general
      mental capability was recorded in 43% of persons studied. There were changes in
      remote CT scanning in 81% of cases, whereas internal hydrocephalus was disclosed
      in 47% of the examined subjects. A high degree of interdependence was found to
      exist between the severity of cranio-cerebral trauma, the remote result of
      therapy and the changes in brain tissues morphology. Definitely the poorest
      therapeutic result was observed in individuals with post-traumatic internal
      hydrocephalus. Wide applicability of Bander's organic test was shown for
      evaluating the character of late psychic consequences in subjects in the remote
      period after cranio-cerebral trauma. In the overwhelming part of cases, the
      observed neurologic-psychological disturbances could be related to changes in
      brain morphology revealed by CT scanning.

PMID- 8154615
TI  - [Effect of hyperthermic and isothermic mud application on hormonal function of
      normal and insufficient corpus luteum in women].
AB  - The aim of the paper has been to study the effect of a single procedure with
      hyper (42 degrees C) and isothermic (37 degrees C) mud exerted on the hormonal
      function of normal and insufficient corpus luteum in women. Procedure with mud
      was the first of its kind sanatorium treatment and consisted in simultaneous use
      of wrapping and vaginal pack. That was performed in the compartment from 18 to 22
      nd day of menstrual cycle in 55 women with normal function of corpus luteum. The
      number included 32 with hyper, and 23 with isothermic mud. In a group of 41
      studied women with insufficient corpus luteum, in 21 hyper and in 20 isothermic
      mud was used. In all the women prior to the procedure, 2 and 5 hours after the
      procedure, the accomplished radioimmunological determinations involved:
      concentration of FSH, LH, progesterone and estradiol in blood serum. Moreover,
      the level of adrenaline and noradrenaline in urine was established by
      fluorimetric method, calculated for gram of creatinine. In 10 of them
      concentration of FSH and LH was being determined every 15 minutes for the first 2
      hours following the procedure. The employed procedure with hyper or isothermic
      mud in a similar manner led to transient increase in the concentration of
      progesterone and estradiol in blood sera of women with normal and insufficient
      hormonal function of corpus luteum. There was also a significant rise in
      excretion of adrenaline and noradrenaline in urine, particularly after
      hyperthermic mud application. The mentioned increase in the concentration of
      steroids was disconnected with the elevation affecting the concentration of
      gonadotropins, but likely due to their discharge from ovaries.

PMID- 8154616
TI  - [Effect of surgery involving ovaries on the level of estradiol and gonadotropins
      in blood serum, with indications for hormonal treatment in early post-operative
      period being taken into consideration].
AB  - The studies cover 124 women operated on at the Clinic of Operative Gynaecology
      IOG--PMA in Szczecin from 1981 to 1991. The blood for testing was collected prior
      to operation as well as in II and VIII 24-hours after the procedure. The material
      was divided into 5 groups: group I--31 patients, in whom one ovary or adnexa were
      removed in the first phase of cycle; group II--31 patients, whose uteri without
      adnexa were removed in the first phase of cycle; group III--31 post-menopausal
      patients, in whom uterus and adnexa were excised; group IV--comprised 31 post
      menopausal patients, in whom uterus with adnexa was excised and subsequently
      estrogenic agents were given; group V--62 patients divided into subgroups A--16
      patients with carcinoma of uterine cervix and ovary, and B--46 patients with
      neoplasm of uterine body. In all the patients FSH, LH, E2 were determined by RIA
      and EIA methods. The results were subjected to statistical analysis and
      elaborated by Student's t-test. The following has been disclosed: a) statistical
      significant diminution of E2 concentration with tendency to an increase in
      concentration of gonadotropins in the reproductive period after the excision of
      ovary and also uterus without adnexa; b) significant decrease in concentration of
      E2 and an increase of gonadotropins after excision of uterus with adnexa in
      patients operated on in the post-menopausal period, which supports the existence
      of ovarian steroidogenesis at this period of life. It has been disclosed that
      there was a significant rise in E2 concentration and a fall in concentration of
      gonadotropins following the application of Oestradiolum depot drug, which
      additionally confirms the activity of the hypothalamo-pituitary-ovarian system
      after menopause. A relation was found between the studied hormones and the basic
      disease, which also proves the function of hypothalamo-pituitary-ovarian system
      after menopause. The results of the studies fully substantiate the use of normal
      prophylaxis of consequences due to wavering of hypothalamo-pituitary-ovarian
      system in the reproductive period, as well as the metabolic consequences after
      menopause. They, however, fail to specify the period of time, at which the
      hormonal treatment may be applied best and most beneficially.

PMID- 8154617
TI  - [Characteristics of uterine contraction curve registered by external tocography
      in imminent premature delivery with tocolytic treatment being given special
      consideration].
AB  - Characteristics of uterine contraction curve was evaluated from recordings
      obtained by means of external topography in imminent premature delivery, as well
      as from comparative analysis of changes of the said characteristics in the course
      of tocolytic therapy. The study covered 19 pregnant women with imminent premature
      delivery symptoms and 12 giving birth "at term", in whom respectively 433 and 142
      uterine contractions were recorded topographically. After digital processing of
      the records with the aid of original software, 10 features of curves for changes
      in the uterine wall tonus, registered in the course of tocolytic therapy by using
      magnesium sulphate, salbutamol and fenoterol, were subjected to retrospective
      computer analysis. It has been disclosed that fenoterol caused the earliest and
      most strikingly expressed changes in the area of analyzed features of the uterine
      contraction curves, while applying higher doses there was a significant
      shortening of overall contraction length, and of the time at respective levels of
      amplitude. Contractions registered in patients with imminent premature
      pregnancies before the onset of tocolytic treatment were characterized by higher
      values of features reflecting changes in intrauterine pressure, but by lower
      values of features associated with the duration of contraction in confrontation
      with the recordings, accomplished for comparison purposes, of delivery "at term"
      in the latent phase.

PMID- 8154618
TI  - [Evaluation of fetal lung maturation in rabbits after giving carnitine and
      carnitine with betamethasone to pregnant rabbits].
AB  - Investigations were carried out on 24 pregnant white New Zealand rabbits and
      their 210 fetuses. Eight pregnant rabbits received intravenous injections of
      carnitine on the 25th, 26th and 27th day of pregnancy, in doses of 80 mg/kg/24
      hours. Eight other pregnant rabbits were given carnitine in the same manner and
      betamethasone intramuscularly on the 25th and 26th day of pregnancy in doses of
      0.1 mg/kg/24 hours. Eight control pregnant rabbits received intravenous and
      intramuscular injections of normal saline. In all the groups caesarean section
      was performed on the 28th day of pregnancy. The contents of lecithin and
      sphingomyelin in lung homogenates of fetuses and in amniotic fluid were
      determined by thin-layer chromatography. The lungs of the fetuses were subjected
      to morphological studies in light and in electron microscopes. The studies proved
      that carnitine given during pregnancy accelerated biochemical and morphological
      maturation of fetal rabbit lungs. However, administration of carnitine in
      combination with betamethasone does not provide better effect than the
      administration of carnitine alone.

PMID- 8154619
TI  - [Selected problems in epidemiology of proliferative diseases of the hematopoietic
      system in children of the western Pomeranian region for 1979-1988].
AB  - On the basis of analysis covering the documentation of I and II Pediatric Clinics
      -PMA in Szczecin, encompassing the Western Pomeranian region with respect to
      specialist care, material concerning proliferative diseases of hematopoietic
      system for 1979-1988 was collected. They were diagnosed in children under the age
      of 15 years. The material was divided into disease groups and subjected to
      mathematical-statistical analysis with due consideration given to the following
      parameters. Total incidence, morbidity according to sex, character of inhabited
      environment, also an analysis was carried out to define the interdependence
      between the appearance of acute leukemias as well as lymphomas, and selected
      factors of the child's family milieu. Differentiation of the coefficient was
      disclosed in morbidity among the children in the individual provinces of the
      studied regions. Statistically significant dependence was revealed between
      disclosure of acute leukemias, lymphomas and all the proliferative diseases on
      the one hand, and sex, character of environment inhabited by children, on the
      other (boys and rural children are affected more frequently). It has been found
      out that there is greater predisposition for acute leukemia and lymphoma to
      affect children suffering more frequently from bacterial infections of
      respiratory tract, and relationship was shown to exist between artificial feeding
      of children in the first 6 months of life, and the appearance of acute leukemias.

PMID- 8154620
TI  - [Influence of prematurity and intrauterine hypotrophy on development of infants
      in the Szczecin population].
AB  - Longitudinal evaluation of development at the infantile period involved 415
      children, born during the period from 1985.12.01 to 1987.03.31 in two Obstetric
      Clinics, PMA, in Szczecin. The studied group comprised 108 eutrophic premature
      infants, 25 premature babies with hypotrophy, 116 full-term neonates with
      intrauterine hypotrophy. The control group was made up of 166 infants born at
      term, being eutrophic neonates. Physical development was analyzed on the basis of
      measuring 13 anthropometric parameters, determined in monthly compartments.
      Evaluation of psychomotoric development was performed by the aid of Denver's test
      in the 3, 6, 9 and 12 month of life. The accomplished studies have disclosed that
      delays in physical and psychomotor development persisted still in the 12th month
      of life in children of the investigated group as compared with the control one.
      Retardations in somatic development were more pronounced in children with
      hypotrophy, while disturbances in psychomotor development were recorded more
      frequently in premature infants, and involved spheres of locomotion and visual
      motorial coordination. In the studied population the achievements in children's
      development were significantly correlated with the degree of maturity after
      birth, and past infectious diseases. Among the environmental factors, an
      essential influence was exerted by the education of parents, social-existential
      conditions of the family as well as cigarette-smoking by the mother.

PMID- 8154621
TI  - [Interaction of fluoride with milk constituents].
AB  - Fluoride concentrations have been studied in cow milk stemming from regions
      variably influenced by fluorine pollution. It was disclosed that fluoride
      concentration in the milk of cows grazing on areas with a high degree of
      environmental contamination by fluorine compounds was about three-fold higher as
      compared to the control group. Fluoride distribution was evaluated in milk, in
      which the protein sediment got separated from the whey. The said distribution was
      found to be equal in both of the milk constituents. Due to the decomposition of
      whey into the whey proteins sediment and the remaining solution, an answer was
      obtained to the question of which part of whey fluoride appeared in the ionized
      form (80%). Studying the binding of fluoride by isolating and purifying the
      fraction of milk proteins at various pH, it was revealed that alpha-lactalbumin
      bound fluoride at 3.9 pH. Because of limited caseins solubility at that pH, there
      was no possibility to find out whether they bound fluoride ions. At fresh milk
      pH, the caseins exist in the anionic form and as such they are unable to bind
      fluoride independently. The binding of fluoride with milk lipids was investigated
      and it was ascertained that about 11% of fluoride being introduced into milk were
      bound to lipid constituent. The study covered also the influence of fluoride ions
      on the magnitude of the optic polarization angle of aqueous lactose solutions in
      different concentrations. That angle undergoes diminution in comparison with
      solutions not polluted by fluoride. Fluoride concentration was defined in some
      milk formulas of Polish production designed for infants. They exceed, depending
      on the kind of formulas, 20-70 fold the average fluoride concentration evidenced
      in human milk. Thus, the differences in fluoride supplied to infants, fed by
      breast and artificially, are very great.

PMID- 8154622
TI  - [Influence of chronic use of lead ions on rat spermatozoa].
AB  - The aim of the paper has been to establish the manner, in which the lead damages
      spermatozoa, and what role in this process is played by epithelial cells of
      epididymis, responsible for maturation and survival of spermatozoa in that organ.
      The studies were carried out on sexually mature male rats, which were given to
      drink lead acetate (II), for 9 months. Studies in vitro were also performed on
      isolated, from epididymis, spermatozoa of rats untreated with lead, but incubated
      in milieu having high concentration of ions of that element. A number of research
      techniques were employed: morphologic examinations of testes and epididymidis,
      with stages of spermic epithelium and epididymal zones being taken into
      consideration; microscopic-electron studies of cells in epididymal duct wall and
      spermatozoa from duct lumen; X-ray microanalysis determining the presence and the
      types of elements on ultrathin specimens of epididymal cells and in spermatozoa;
      histochemical examinations for oxidoreductase of spermatozoa. Lead deposits were
      found in cells of the epididymal duct and lumen. The most of such deposits were
      revealed in epithelial cells, through which substances from the blood vessels are
      transported to the duct lumen-to spermatozoa. That gives rise to the possibility
      of damaging spermatozoa, which had been verified by microscopic-electron and
      histochemical examinations of spermatozoa. The vitro studies disclosed the
      ability of lead to penetrate spermatozoa, particularly the midpiece. Very
      important is the conclusion highlighting that the presence of lead deposits in
      epithelial cells and in the lumen of epididymal duct supports the possibility of
      excreting this element from the organism of mammals with the semen.

PMID- 8154623
TI  - [Experimental evaluation of the effect of pollen extract on the course of
      paracetamol poisoning].
AB  - Studies were performed on 670 male mice of Swiss strain. Cernilton (mixture of
      preparation Cernitin T-60-100 mg/kg and Cernitin GBX--20 mg/kg emulsified by
      using Imwitor 370) was intraperitoneally administered in a volume of 30 ml/kg of
      body mass. LD50 of paracetamol was fixed after intraperitoneal administration.
      Certimilton was given 1 h before or 1 h after paracetamol in a dose LD100 and
      LD50, thereafter the survival time and the number of deceased animals were
      determined. The effect of Cernilton preparation on the lesion of the liver
      induced by paracetamol was studied in 5 groups with 10 mice each: group 1-
      control; group 2--paracetamol; group 3--Cernilton, after 1 h paracetamol; group 4
      -paracetamol; after 1 h Cernilton; group 5--Cernilton. Paracetamol was injected
      in the following manner: a--300 mg/kg in a single dose, estimation after 3 h, b-
      300 mg/kg in single dose--section after 24 h, c--230 mg/kg/24 h single dose-
      estimation after 24 h, d--230 mg/kg/24 h four times--section after 24 h, e--230
      mg/kg/24 h--seven times--estimation after 24 h. The degree of hepatic lesion was
      evaluated on the basis of the activity of alanine and asparagine aminotransferase
      as well as alkaline phosphatase, total bilirubin concentration in serum, the
      content of reduced glutathione and cytochrome P-450 in the liver as well as
      histological and histochemical examinations (glycogen, lipids) of the liver. It
      has been disclosed that Cernilton increases the survival rate of animals and
      decreases the hepatic lesion in the course of acute paracetamol intoxication,
      Cernilton is the factor that effectively normalizes the biochemical and
      morphological indices of hepatic lesions having been caused by repeated use of
      toxic paracetamol dose. The therapeutic action of pollen extracts is more
      effective than prophylactic one. The role of glutathione is significant in the
      mechanism of protective activity of the pollen extract.

PMID- 8154624
TI  - [Effect of pollen extracts (cernitin preparation) on selected biochemical
      parameters of liver in the course of chronic ammonium fluoride poisoning in
      rats].
AB  - The aim of the paper has been the experimental evaluation of protracted exposure
      to ammonium-fluoride vapours exerted on selected biochemical parameters in serum
      as well as microsomal fraction of the liver in animals. An attempt was made to
      ameliorate eventual changes by using Cernitin preparation. The experiment was
      performed on male rats of Wistar strain. The rats were exposed to NH4F in a
      toxicological chamber with controlled parameters. Cernitin was added to standard
      diet and given to animals in the form of balls. The studies were carried out
      after 3 and 6 month-long exposure. The range of the performed studies covered:
      activity of enzymes (AspAT, AlAT, AP, ChE) and content of bilirubin as well as
      lipids were studied in the blood serum. Content of proteins, cholesterol and
      phospholipids was investigated in the liver homogenate. It has been shown that
      chronic exposure to NH4F vapours causes a rise in the activity of studied
      aminotransferases and alkaline phosphatase, and a decreases in activity of
      cholinesterase. The changes in activity were accompanied by an increase in the
      content of lipids. Prophylactic application of Cernitin preparation normalizes
      the disorder involving the studied enzymatic and lipid parameters.

PMID- 8154625
TI  - [Diffusion of lipid fractions through the barrier of cantharidin blisters in
      hyperlipidemias under conditions of clofibrate and rutinosid interaction].
AB  - Diffusion of lipid fractions from blood to fluid in blister induced by
      cantharidal ointment, applied on the forearm skin, was studied in 54 patients,
      thereof 18 with normlipidemia, 13 having type II hyperlipidemia, 23 with type IV
      hyperlipidemia. Concentrations of triglycerides, phospholipids, free fatty acids,
      total cholesterol, HDL-cholesterol and LDL--cholesterol were studied in blood and
      fluid before treatment, 10 days after applying clofibrate, 20 days after
      clofibrate application, and 10 days following the application of rutinosid, i.e.
      upon completion of therapy. After the treatment it was observed that in all the
      patients the concentration of lipid fractions in blood was lowered, except for
      HDL-cholesterol, the level of which was elevated, as was the concentration of all
      the fractions in the blister fluid. Lipid concentration in serum, with the
      exception of free fatty acids, was invariably higher than in blister fluid. Free
      fatty acids, LDL-cholesterol and HDL-cholesterol diffused from blood to fluid in
      a greater percentage. Lipid fraction concentration in fluid depended mainly on
      the concentration of HDL-cholesterol and triglycerides in the blood. In
      normlipidemia, the highest percentage of lipid fractions was diffused to blister
      fluid; the percentage was lower in type IV hyperlipidemia, the lowest being in
      type II hyperlipidemia. Clofibrate hypolipemia action correlated best with with
      HDL-cholesterol and triglyceride activity. After the treatment, the elevated
      diffusion of all the fractions from blood to blister fluid was, in my opinion,
      consistent with lipid metabolism, venoruton, as vessel tightening drug, may play
      a protective role in relation to endothelia in hyperlipidemia.

PMID- 8154626
TI  - A warning shot has been fired across our bow--did we notice? In Oregon, the
      future is now.

PMID- 8154627
TI  - Rhinitis.
AB  - Rhinitis is a problem causing significant morbidity. The etiology of rhinitis is
      varied. The pathophysiology of rhinitis is just beginning to be elucidated.
      Allergic rhinitis is primarily understood as an inflammatory disease with a
      neurogenic component. Disease states such as responses to cold dry air are
      primarily considered to be neurogenic in origin, but inflammatory cells and
      mediators play a significant role in the development of symptoms in these
      patients. Our understanding of these complex interactions is reflected in the
      pharmacologic interventions currently available. Most rhinitis therapy addresses
      the symptoms of rhinitis not the underlying disease state. Future research in the
      field of rhinitis should increase our knowledge of the pathophysiology and
      therefore assist in new drug development.

PMID- 8154628
TI  - AIDS-associated Reiter's syndrome.
AB  - Classically, Reiter's syndrome was defined as a triad of arthritis, urethritis,
      and conjunctivitis. In 1981, the American Rheumatism Association revised its
      defining criteria for Reiter's syndrome as an episode of peripheral arthritis of
      more than 1 month's duration occurring in association with urethritis and/or
      cervicitis. Reiter's syndrome is also associated with mucocutaneous lesions.
      Reiter's syndrome was first described in association with the human immuno
      deficiency virus (HIV) in 1987. The course of Reiter's syndrome in HIV is more
      severe, progressive, and refractory to treatment than in non-HIV-positive
      patients. The immunopathogenesis of Reiter's syndrome is linked to HLA-B27, which
      has been described as the disease susceptibility factor. The association of
      Reiter's syndrome and HLA-B27 positivity is 80%. Infectious agents may play a
      critical role in the initiation or perpetuation of Reiter's syndrome. It has been
      suggested that an amino acid sequence within the HLA-B27 molecule allows
      microbial peptides to bind and be presented to T cytotoxic cells (CD8), which
      results in a primary T cytotoxic cell response against various tissues. The role
      of the HIV in the pathogenesis of Reiter's syndrome is still being investigated.
      Human immunodeficiency virus may directly cause arthritis; it may increase the
      host's susceptibility to infection with arthritogenic organisms. Additionally,
      HIV infection increases the relative number of CD8 cells, which may play a key
      role in the pathogenesis of Reiter's syndrome. In this article, we present a case
      of Reiter's syndrome in an HLA-B27 and HIV-positive patient, and a review of the
      literature on the infectious, immunologic, and dermatologic aspects of Reiter's
      syndrome in HIV disease.

PMID- 8154629
TI  - Food allergy and food intolerance--what is the difference?
AB  - The literature is contradictory concerning the use (and misuse) of the terms
      "food allergy" and "food intolerance." When using double-blind, placebo
      controlled food challenge as the gold standard, the clinical picture
      characterizing both diseases is identical, ie, concomitant signs and symptoms
      from the skin, gastrointestinal-tract and respiratory system (classical allergic
      signs and symptoms). A distinction between food allergy and food intolerance thus
      depends on whether the involvement of the immune system can be verified. The
      basic problem with diagnostic tests such as skin prick test (SPT), measurement of
      specific IgE (RAST) or histamine release from basophils (HR) is that in contrast
      to inhalant allergens, no standardized extracts are commercially available. It is
      therefore often not possible to discriminate between the ability of a test per se
      in the diagnosis of food allergy and differences in allergen extract quality.
      This is probably the reason for the great variability in diagnostic sensitivity
      and specificity reported in the literature. Many cases of food allergy to
      proteins may be therefore misdiagnosed as food intolerance due to a low
      sensitivity of the tests (SPT, RAST, and HR) used.

PMID- 8154630
TI  - Modified method of nonspecific nasal provocation with histamine for routine use.
AB  - An improved method for assessment of nonspecific nasal reactivity (NNR) was
      evaluated to validate it, and determine a criterion for nasal hyperreactivity.
      The efficacies of four different parameters to indicate nasal patency in
      assessment of the level of NNR were compared in 60 healthy subjects and 65
      patients with allergic rhinitis (37 in the period of pronounced symptoms and 28
      in the symptom-free period). Histamine/diphosphate was sprayed into both nostrils
      every three minutes in doubling concentrations (0.03125 to 32 mg/mL); during 90
      seconds, sneezes were counted and symptom score was assessed; thereafter nasal
      inspiratory peak flow (NIPF), total nasal airway resistance (NART), nasal forced
      expiratory volume in one second (N-FEV1) and nasal midexpiratory flow rate (N
      MEF25/75) were measured. Nasal inspiratory peak flow meter (Youlten, "Airmed")
      was used to measure NIPF. A spirometer (Pneumoscreen II, "Jaeger") with a face
      mask attached was used to measure NART, N-FEV1, and N-MEF25/75. The test of NNR
      was terminated when a significant change of values (as determined by a pilot
      study) occurred: NIPF, -30%; NART, +75%; N-FEV1, -20%; and N-MEF25/75, -25%. Our
      results indicate a significantly higher NNR (PCNART of patients = 0.77 mg/mL
      versus PCNART of healthy subjects = 4.5 mg/mL; P < .00001) period of pronounced
      symptoms than in healthy subjects or in rhinitic patients when symptom free. A
      criterion, that takes age into account, is set for separation of normoreactivity
      from hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154631
TI  - Effect of budesonide on bronchial hyperresponsiveness and pulmonary function in
      patients with mild to moderate asthma.
AB  - Thirty-nine subjects were included in this double-blind, placebo-controlled study
      of bronchial hyperresponsiveness (BHR) in patients with mild to moderate asthma.
      The time-courses of change of FEV1, PEFR%, bronchial reactivity, and daily
      measures of asthma control were determined during 8 weeks of treatment after a
      run-in period of 2 weeks. Bronchial hyperresponsiveness was assessed by the
      methacholine provocation method, defined as the dose of methacholine causing a
      20% fall of FEV1 compared with baseline values. The trends of FEV1 and the
      percentage change in PEFR from baseline were significantly different between
      groups, in favor of budesonide (P < .05). Patient assessments of the effect of
      treatment showed that PEF improved significantly in the budesonide group only.
      The budesonide group increased their tolerability for methacholine provocation by
      1.8 DD (doubling dose), which tended to be higher compared with the 0.8 DD of the
      placebo group. It is evident from this study and previous studies that more data
      are needed to establish the dose-effect relationship with time and severity of
      the disease.

PMID- 8154632
TI  - Comparison of the bronchodilator response to albuterol administered by the
      OptiHaler, the AeroChamber, or by metered dose inhaler alone.
AB  - Eighteen subjects with moderate asthma participated in this double-blind study
      comparing the bronchodilator response to albuterol or placebo used in conjunction
      with three inhalation devices; the metered dose inhaler (MDI) actuator alone, the
      AeroChamber, and the OptiHaler. The principal comparison was the increase in FEV1
      over 30 minutes. Also recorded were heart rate, time required to use each device,
      and patient acceptance of each device. There was a large bronchodilator response
      with albuterol with each of the devices, but there was no difference in the
      promptness or the magnitude of the bronchodilator response among the three
      devices. There was a small but statistically significant increase in heart rate
      which did not differ among devices. Subject ratings of acceptability were MDI
      alone best, followed by OptiHaler, then AeroChamber. We conclude (1) the
      bronchodilator response obtained with use of the MDI alone, the AeroChamber and
      OptiHaler were not significantly different; (2) patients, as a group, found the
      MDI required less time to use and they favored it over either spacer; (3) while
      in subjects employing good MDI technique, the addition of either an AeroChamber
      or an OptiHaler did not improve bronchodilator response. Spacers may have a role
      in those with poor inhaler technique or in conjunction with inhaled
      corticosteroids.

PMID- 8154633
TI  - Delayed allergic reaction to cefonicid.
AB  - We report a case of delayed cutaneous reaction to intramuscular treatment with
      cefonicid, a second generation cephalosporin. An isolated late skin test response
      was observed to cefonicid only and not to other beta-lactams. A patch test with
      cefonicid 1% was positive after 48 and 96 hours.

PMID- 8154634
TI  - Contact dermatitis from nitroglycerin.
AB  - Although contact dermatitis is cited among the side effects of topical
      application of nitroglycerin, in the majority of cases the reactions are caused
      by an irritant mechanism, and it is only rarely due to an allergic mechanism. We
      present two patients with allergic contact dermatitis and review the existing
      bibliography.

PMID- 8154635
TI  - Effect of RG 12525, a new leukotriene antagonist, on pulmonary function of
      asthmatic adults.
AB  - RG 12525 is a new oral leukotriene D4 (LTD4) antagonist with proven activity in
      animal and human models of leukotriene-induced bronchoconstriction. In this
      randomized, double-blind, parallel-group, placebo-controlled study the
      bronchodilator effects of single oral doses of RG 12525 of 25 and 200 mg or
      placebo were evaluated in 62 adult asthmatic patients. All patients had
      previously demonstrated 20% reversibility of FEV1 with an inhaled beta-agonist.
      They had an unmedicated FEV1 less than 80% of predicted value at the time of the
      study. Bronchodilator activity was assessed by spirometry before and at multiple
      time points after dosing for eight hours. A single 200-mg dose of RG 12525 of mg
      resulted in statistically significantly greater increases in mean maximum change
      above baseline for FEV1 and FEF25-75% than placebo. The peak effect was observed
      four to five hours after dosing. The RG 12525 dose of 25 mg dose induced better
      bronchodilation than placebo but the differences were not significant. Adverse
      clinical experiences or laboratory abnormalities were not noted.

PMID- 8154636
TI  - Increased interleukin-4 production in response to mast cell mediators and human
      type I collagen in patients with rheumatoid arthritis.
AB  - Mast cell synovial hyperplasia can occur in patients with rheumatoid arthritis.
      Histamine can accelerate synovitis and heparin can inhibit lymphocyte function.
      Since interleukin-4 (IL-4) can stimulate murine mast cell and IgE synthesis, we
      determined whether mast cell mediators and anti-IL-4 might effect lymphocyte
      proliferation from patients with rheumatoid arthritis. Twenty-four patients with
      rheumatoid arthritis and nine normal controls were evaluated by history, physical
      examination, physician and patient-assessed joint and allergic symptoms, and
      diary scores. An IL-2-driven-T cell (3H) Tdr proliferation assay with monoclonal
      anti-IL-4 and a sensitive ELISA were performed with isolated peripheral blood
      mononuclear cells (PBMC) with 10 micrograms/mL of either concanavalin A (Con A),
      type I human collagen, or heparin and 10(-6) M histamine. Increased lymphocyte
      proliferation indices with Con A (mean 21.69 +/- 4.9; 6.54 +/- 3.2 normal
      controls), type I human collagen (mean 2.17 +/- 0.52; 1.1 +/- .17, normal
      controls), histamine (mean 1.66 +/- .36; 0.62 +/- 0.08, normal controls), heparin
      (mean 1.61 +/- .38; 0.69 +/- .11, normal controls) occurred in peripheral blood
      mononuclear cells from all patients with rheumatoid arthritis compared with
      normal controls (P < .0236 to .0015) which was inhibited in 32% of peripheral
      blood mononuclear cells by anti-IL-4. Increased IL-4 ELISA levels in cultured
      supernatants were noted with heparin (P < .25) and collagen (P < .05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8154637
TI  - The importance of eosinophils in the immunology of asthma and allergic disease.
AB  - Immunologic concepts of asthma and related allergic diseases are undergoing
      revolutionary changes. Research into immunologic mechanisms has typically focused
      on the acute anaphylactic component, that is, on the role of mast cells and
      immunoglobulin E. Briefly, when a multivalent allergen cross-links IgE molecules
      bound to high-affinity Fc epsilon receptors on the mast cell surface, the cells
      release chemical mediators that constrict the bronchi, dilate blood vessels,
      cause edema, and recruit eosinophils. Recent investigation, utilizing
      bronchoscopic lavage and biopsy and cell biology, is emphasizing chronic
      eosinophilic airway inflammation and is clarifying the mechanisms of a complex
      multicellular chain of reactions that involve not only mast cells and basophils,
      but lymphocytes, eosinophils, endothelial cells, and epithelial cells, and may
      also involve platelets, macrophages, and neutrophils. The airways contain
      activated TH2-like lymphocytes that release cytokines which recruit and activate
      eosinophils. These cytokines also generate adhesion molecules on endothelial cell
      surfaces that promote diapedesis of the eosinophils out of the circulation into
      the submucosa, mucosa, and lumen of the airway. In the tissues, the eosinophils
      degranulate, releasing toxic proteins that damage the respiratory epithelium and
      account for many of the histopathologic abnormalities of asthma.

PMID- 8154638
TI  - How environment affects patients with allergic disease: indoor allergens and
      asthma.
AB  - Progressive changes in American housing and life styles have been associated with
      increased prevalence of allergen sensitization and asthma. Not only have there
      been large increases in the proportion of time spent indoors, but many of the
      changes made in houses are likely to increase exposure to indoor allergens. Thus,
      higher mean indoor temperatures, reduced ventilation, cool wash detergents, and
      the widespread use of carpeting are all changes that could have increased the
      levels of allergens in American homes. Over the past 15 years, dust mites,
      cockroaches, and cats have been identified as major sources of indoor allergens.
      The combination of exposure and sensitization to one of these allergens is
      significantly associated with acute asthma. Furthermore, clinical studies have
      shown a direct quantitative correlation between dust mite allergen exposure and
      the prevalence of both sensitization and asthma. New evidence suggests that
      reductions in allergen exposure may improve asthma symptoms, leading to decreased
      inflammation and bronchial hyperreactivity. Furthermore, as understanding of
      sources of allergens increases, the protocols for decreasing exposure become
      better defined and relatively easy to implement.

PMID- 8154639
TI  - Management of patients with acute asthma: what do we know? What do we need to
      know?
AB  - Management of patients with acute, severe asthma mandates the use of
      comprehensive monitoring and aggressive therapeutic drug regimens. Global
      clinical and objective assessment criteria can help determine the severity of the
      acute episode and will also help determine optimal management protocols. The
      response to aggressive therapy, rather than the initial severity of the attack,
      predicts outcome. Beta 2 sympathomimetic agents are the treatment of choice for
      acute asthmatic episodes. Aminophylline and parasympatholytic agents may be
      useful adjuvants, but more data are needed before firm conclusions can be reached
      regarding risk-benefit ratios. The optimal timing of steroid therapy is not yet
      known, but even this form of treatment is slow in producing results.

PMID- 8154640
TI  - Management of patients with chronic asthma: controversies and future directions.
AB  - Hospitalizations and mortality due to asthma have increased, despite advances in
      asthma treatment. Several aspects of the management of patients with chronic
      asthma are under discussion in efforts to address this problem. Therapeutic
      interventions, including the use of theophylline, corticosteroids, and beta 2
      agonist chronotherapy, will be reviewed, with the goal of defining ways of
      attaining the optimal response when using pharmacologic and nonpharmacologic
      regimens in the treatment of patients with chronic asthma.

PMID- 8154641
TI  - Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas
      in the general population.
AB  - OBJECTIVE: To determine the prevalence of focal lesions of the pituitary gland
      that suggest the presence of a pituitary adenoma in asymptomatic persons. DESIGN:
      100 normal volunteers (70 women, 30 men; age range, 18 to 60 years old) were
      studied by high-resolution magnetic resonance imaging (MRI) of the pituitary
      gland before and after administration of gadolinium-diethylenetriaminepentaacetic
      acid (Gd-DTPA). SETTING: Occult pituitary adenomas are identified at autopsy in
      3% to 27% of unselected asymptomatic patients. The frequency of incidental
      pituitary adenomas detected by MRI in normal persons is unknown. MEASUREMENTS:
      The MRI scans from volunteers were randomly mixed with scans of 57 patients with
      Cushing disease and interpreted independently by three blinded reviewers.
      RESULTS: Seven women (10%) and three men (10%) had focal areas of decreased
      signal intensity in the pituitary gland after administration of Gd-DTPA. The
      lesions ranged from 3 to 6 mm in greatest diameter and were diagnosed as
      pituitary adenomas by at least two of the three reviewers. When similar lesions
      were detected on MRI scans in patients with Cushing disease, the positive
      predictive value for identification of an adenoma at that site was 86%.
      CONCLUSIONS: About 10% of the normal adult population have pituitary
      abnormalities on MRI scans that are compatible with the diagnosis of asymptomatic
      pituitary adenomas. Most pituitary adenomas remain asymptomatic and do not
      require treatment.

PMID- 8154642
TI  - Oral contraceptive use and mortality during 12 years of follow-up: the Nurses'
      Health Study.
AB  - OBJECTIVE: To examine prospectively the risk for mortality among women who had
      ever used oral contraceptives compared with those who had never used oral
      contraceptives. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study.
      PARTICIPANTS: 166,755 women aged 30 to 55 years in 1976, followed through 1988
      (1.3 million person-years of follow-up). RESULTS: On the basis of 2879 deaths, we
      found no overall difference in mortality among women who had ever used oral
      contraceptives compared with women who had never used oral contraceptives; the
      relative risk for ever-users, adjusted for age, body mass index, and cigarette
      smoking was 0.93 (95% CI, 0.85 to 1.01). We observed no trend in risk for total
      mortality with increasing duration of past use of oral contraceptives. After
      adjusting for age, body mass index, and cigarette smoking, women who had used
      oral contraceptives for 10 or more years had a relative risk of 1.06 (CI, 0.83 to
      1.35). CONCLUSION: Use of oral contraceptives is safe; no evidence from this
      study indicates that long durations of oral contraceptive use adversely affect
      long-term risk for mortality.

PMID- 8154643
TI  - Ceftazidime compared with piperacillin and tobramycin for the empiric treatment
      of fever in neutropenic patients with cancer. A multicenter randomized trial. The
      Intercontinental Antimicrobial Study Group.
AB  - OBJECTIVE: To compare piperacillin and tobramycin with ceftazidime alone for the
      empiric treatment of fever in the neutropenic patient without evidence of skin
      infections or anaerobic infections. DESIGN: A multicenter, randomized, controlled
      trial. PATIENTS: 876 febrile, neutropenic episodes in 696 patients (83% acute
      leukemia or bone marrow transplantation); 92 episodes were excluded from analysis
      because of protocol violation. INTERVENTIONS: Patients received either
      intravenous ceftazidime (2 g every 8 h) or piperacillin (12 to 18 g/d in 4 to 6
      divided doses plus tobramycin (1.7 to 2.0 mg/kg body weight every 8 h). Treatment
      could be modified at any time at the discretion of the investigator.
      MEASUREMENTS: Percentage of satisfactory response, eradication of the infecting
      organism, development of superinfections, and occurrence of adverse events.
      RESULTS: As a single agent, ceftazidime was as effective as the combination of
      piperacillin and tobramycin (62.7% satisfactory responses compared with 61.1%;
      odds ratio, 1.07%; 95% Cl, 0.79 to 1.44; P > 0.2). Equivalent responses were also
      obtained in episodes of profound neutropenia (odds ratio, 0.76; Cl, 0.43 to 1.33;
      P > 0.2). Infectious mortality was 6% for ceftazidime and 8% for the combination
      therapy. Eradication of the infecting organisms was achieved in 79% of bacteremic
      episodes treated with ceftazidime compared with 68% of the episodes treated with
      the combination therapy (odds ratio, 1.76; Cl, 0.92 to 3.38; P = 0.08), and rates
      for gram-negative rod bacteremia were also similar (95% compared with 77%; odds
      ratio, 5.25; Cl, 1.0 to 27.5; P = 0.03). Superinfections developed in 38 episodes
      in each group. An adverse event occurred in 8% of episodes treated with
      ceftazidime compared with 20% of episodes treated with combination therapy (P <
      0.001). CONCLUSION: Ceftazidime alone was as effective but safer than the
      combination of piperacillin and tobramycin for the empiric treatment of febrile,
      neutropenic patients, even those with profound and prolonged granulocytopenia.

PMID- 8154644
TI  - Postpartum thrombotic thrombocytopenic purpura (TTP) complicating pregnancy
      associated immune thrombocytopenic purpura (ITP)

PMID- 8154645
TI  - The association between cholesterol and death from injury.
AB  - PURPOSE: To review the association between low serum cholesterol and death from
      injury. DATA SOURCES: Relevant English-language papers identified through MEDLINE
      and Current Contents searches and bibliographies of identified articles. STUDY
      SELECTION: More than 150 articles were reviewed to identify data, meta-analyses,
      or important reviews of the association between low cholesterol and injuries.
      DATA EXTRACTION: Estimates of the association between cholesterol and death from
      injury were extracted from published reports. DATA SYNTHESIS: Animal studies and
      descriptive studies have provided little information about serum cholesterol and
      injuries. The Conference on Low Blood Cholesterol pooled results from 14 cohort
      studies in men and found a relative risk of 1.4 for death from injury in men
      whose cholesterol levels were lower than 4.14 mmol/L (160 mg/dL) compared with
      men whose cholesterol levels were 4.14 to 5.15 mmol/L (P = 0.003). Most cohort
      studies support this finding. The strongest evidence that cholesterol and death
      from injury are related comes from a meta-analysis of six randomized cardiac
      primary prevention trials of cholesterol reduction; the relative risk for death
      from injury for treated men compared with controls was 1.42 (95% Cl, 0.94 to
      2.15). CONCLUSIONS: In cohort studies, the strength of the association between
      low serum cholesterol levels and subsequent death from injury is weak and may be
      caused by confounding factors such as socioeconomic status. The modestly elevated
      risk ratio found in a meta-analysis of trials of cholesterol reduction in men is
      of borderline statistical significance. This association may be related to
      efforts to lower cholesterol rather than to low absolute levels of serum
      cholesterol. Until more data are available, the hypothesized relation between low
      cholesterol and injuries remains unsettled.

PMID- 8154646
TI  - Magnetic resonance imaging of the brain and spine: a revised statement. American
      College of Physicians.

PMID- 8154647
TI  - Holding GUSTO up to the light. Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries.
AB  - The Global Utilization of Streptokinase and Tissue Plasminogen Activator for
      Occluded Coronary Arteries (GUSTO) trial, a recent randomized "megatrial" of
      thrombolytic therapies in acute myocardial infarction, showed a statistically
      significant decrease of 30-day mortality in patients treated with accelerated
      dose tissue plasminogen activator (tPA) compared with streptokinase. The
      therapeutic and cost implications of the results have been intensely scrutinized,
      and several commentaries have been written on the interpretation of the study.
      Questions have been raised about the treatment benefit in certain subgroups, the
      validity of the results because of the open-label design, the relevance of a 1%
      absolute benefit in mortality rates, the cost-effectiveness of the drug, and the
      generalizability of the results. These issues are all important considerations
      for translating the results of this study into clinical practice worldwide. This
      article sheds additional light on the interpretation of GUSTO, clarifies
      misconceptions that may have clouded understanding of the trial results, and
      discusses the contributions of this trial in advancing our understanding of
      modern myocardial reperfusion therapy.

PMID- 8154648
TI  - Thrombolytic agents: the science of the art of choosing the better treatment.

PMID- 8154649
TI  - "In the balance": weighing the evidence.

PMID- 8154650
TI  - Therapeutic theophylline levels and adverse cardiac events.

PMID- 8154651
TI  - Is preventing sudden cardiac death realistic?

PMID- 8154652
TI  - Phenytoin and ranitidine interaction.

PMID- 8154653
TI  - Sun exposure and amyotrophic lateral sclerosis.

PMID- 8154654
TI  - A conflict of interest "revisited": the use of stereotypes.

PMID- 8154655
TI  - A conflict of interest "revisited": the use of stereotypes.

PMID- 8154656
TI  - [Diagnosis of hyperparathyroidism].

PMID- 8154657
TI  - [Primary hyperparathyroidism: surgical approach].

PMID- 8154658
TI  - Results and complications of the surgical treatment of primary
      hyperparathyroidism.
AB  - Between the late 1960's and 1980, the operation for primary hyperparathyroidism
      at The University of Chicago changed from subtotal parathyroidectomy for all
      patients to removal of an adenoma with performance of biopsies of all other
      normal glands. After 1980, our technique was again modified to bilateral neck
      exploration, resection of the adenoma when it was present, and performance of
      fewer biopsies of normal glands (usually one and sometimes two). Between 1980 and
      1990, 308 parathyroidectomies were performed; 288 patients underwent first
      operations. Two hundred forty-five (85.1%) of these patients had an adenoma and
      forty-three (14.9%) had hyperplasia (multiglandular disease); none had a
      carcinoma. Resolution of hypercalcemia with the first operation was achieved in
      281 patients (97.5%); seven patients experienced failed explorations. The early
      cure was the same whether or not preoperative localization studies were
      performed. Biopsy of fewer normal parathyroid glands when an adenoma was present
      resulted in a decreased incidence of transient postoperative hypocalcemia.
      Nineteen patients underwent 20 reoperative parathyroidectomies during this
      period. Preoperative localization studies; done in 16 (80%) of 20 cases, were
      very helpful. Ninety percent of patients with abnormal parathyroid glands in
      their neck or mediastinum were cured with their initial reoperation.

PMID- 8154659
TI  - [Surgical approach in the treatment of recurrent primary hyperparathyroidism].
AB  - Recurrent or persistent primary hyperparathyroidism (HPT) is a rare occurrence
      requiring generally a careful reoperation. From 1980 to 1992 a total of 192
      patients underwent bilateral cervical exploration following a diagnosis of
      primary hyperparathyroidism. Persistent of recurrent HPT was found in 6 (3.04%)
      of our cases. In two patients a subtotal parathyroidectomy was performed
      (parathyroid hyperplasia) and hyperfunctioning parathyroid tissue was found at
      neck exploration. In one case an ectopic adenomatous fifth gland was found in
      mediastinum at reoperation. Three patients with recurrent HPT had a parathyroid
      carcinoma but in only two cases it was possible to identify and remove the
      pathologic tissue preoperatively localised in mediastinum by double-tracer
      scintigraphy and CT scan 6 and 15 months after first operation respectively. The
      third patient with parathyroid carcinoma was inoperable on account of multiple
      metastases both cervical and thoracic.

PMID- 8154660
TI  - [Role of diagnostic imaging in primary and secondary hyperparathyroidism].
AB  - The authors take in consideration the sensitivity of imaging methods in
      localization of adenomas and hyperplastic glands in primary and secondary
      hyperparathyroidism. Advantages and limits of Ultrasound, Computed Tomography,
      Magnetic Resonance Imaging and Dual Isotope Subtraction Scintigraphy are
      considered, specifying the correct technique of execution and the indications for
      each examination. The sensitivity of these imaging methods is fairly good, but
      inferior in comparison to surgical exploration of the neck; it has been seen that
      this value improves sensibly when a two-study combination is considered as a
      single test. After a wide review of the literature and considering their
      experience, the authors stress the opportunity of a routinary preoperative use of
      diagnostic imaging, both in primary intervention and in case of reintervention.
      According to the authors US and MRI are the best imaging modalities: US are of
      simple execution, non-invasive and have a high sensitivity in the localization of
      adenomas in the typical location; MRI is a multiplanar technique, has a high
      contrast resolution and a very good capability of exploring the neck and
      mediastinum, allowing the localization of ectopic adenomas.

PMID- 8154661
TI  - Renal hyperparathyroidism following kidney transplantation.

PMID- 8154662
TI  - The effects of colloidal and crystalloidal fluids on acidosis and lactacidemia in
      cardiopulmonary bypass.
AB  - During extracorporeal cardiac surgery it is difficult to measure the severity of
      metabolic acidosis thru arterial bloods gas determination. During bypass surgery
      a decrease in Colloidosmotic Pressure (COP) may influence the degree of acidosis.
      We studied 90 patients in whom the following parameters were measured before, 30
      minutes after beginning bypass, immediatly after bypass, upon arriving bypass,
      upon arriving in the Intensive Care Unit (ICU) and upon discharge (ICU): pH,
      lactic, acid, pO2, pCO2, base excess correlating them with COP. There is a
      relation between COP and lactic acid, COP = 21.39-0.17 Lactic Acid, with p <
      0.001. There is a inverse lineal correlation between COP and blood lactic acid
      levels. A greater COP was found with a lower blood lactic acid levels. We
      recommend the use of colloids perfusion as priming fluid instead of electrolytes
      solutions, specially in patients in extreme ages and also in those in whom a
      prolonged bypass time is foreseen. This may prevent an increase in blood lactic
      acid levels.

PMID- 8154663
TI  - [Adenolipoma (thyrolipoma) of the thyroid gland].

PMID- 8154665
TI  - [Pathology and clinical course of pancreatic pseudocyst].
AB  - According to the literature and the personal experience of the authors there seem
      to exist many controversies on the treatment of pancreatic pseudocysts, partly
      due to the lack of definitions and to the fact that prognosis is different based
      upon the pathophysiology of the lesions. We report 4 cases of pancreatic
      pseudocysts successfully treated with a multidisciplinary approach, stressing the
      role of pharmacology and of artificial nutrition and endoscopy on the outcome of
      these lesions.

PMID- 8154664
TI  - Duodeno-jejunal tumors. Report of 9 cases and literature review.
AB  - Nine patients with tumors of the duodenum and the jejunum are described herein
      and the Literature is reviewed. Of the six patients with a duodenal tumor, five
      had an adenocarcinoma and one a Brunner's gland adenoma. A predominance of
      inframpullary tumors was observed within the duodenum. Jaundice and abdominal
      pain were, respectively, the most common presenting symptoms of the tumors
      localized in the periampullary and inframpullary region. Treatment was curative
      in four and palliative in two cases. Duodenopancreatectomy was the treatment of
      choice for periampullary tumors whereas segmental resection was performed in the
      only resectable distal duodenal tumor. Of the three patients with jejunal
      neoplasms, one had an adenocarcinoma arising in the efferent loop of a Billroth
      II gastrojejunostomy performed 40 years before and two had an high malignant
      lymphoma. All three the tumors could be resected. According to the Literature,
      our results show that: 1. The diagnosis of duodeno-jejunal tumors is usually
      late: 2. Although of critical importance in the improvement of the overall
      diagnostic accuracy, endoscopy may be inconclusive or even misleading if the
      entire duodenum is not explored; 3. If duodenopancreatectomy is mandatory for
      periampullary tumors, segmental resection seems to be an adequate procedure for
      tumors of the distal duodenum since it does not ignore lymphatic nodes, can be
      easily performed and has a low postoperative complication rate.

PMID- 8154666
TI  - [Intraoperative colonoscopy: current indications].
AB  - From January 1987 to December 1991, 37 patients underwent intraoperative
      colonoscopy for several indications; these latter can be summarized in the need
      to define the site or extension of the lesions treated or detected by endoscopy
      before surgery. This procedure is therefore necessary in those cases in whom
      intraoperative endoscopy is likely to be useful in planning the surgical
      treatment. The use of intraoperative colonoscopy should be however considered
      complementary, but not substitutive, of the preoperative colonoscopy.

PMID- 8154667
TI  - [Evaluation of the tolerance of a lipid emulsion administrated during total
      parenteral nutrition in surgical patients].
AB  - Tolerance's evaluation of a lipid emulsion given in course of parenteral total
      nutrition in surgical patient's. The first fat emulsions for intravenous
      application were thrown on the market in the 1920's years. Authors make a study
      on a limited sample of surgical patients about type and incidence of both
      immediate and late adverse reactions versus intravenous administration of
      Lipofundin S. They also suggest, on the same time, a protocol for the survey of
      these reactions. The results suggest a good tolerance to Lipofundin S intravenous
      administration and no influence on haematic biochemical parameters.

PMID- 8154668
TI  - [Scleronodular retrosternal Hodgkin's disease with cervical protrusion].
AB  - The case of a retrosternal localization of Hodgkin disease is a very infrequent
      one, and its presentation as an inflammatory tumor is exceptional indeed. This
      case report of a young woman affected by a cervical tumour projecting in front of
      the sternal bone, both with fever and tenderness, gave a mistaken address toward
      a diagnosis of suppurative thyroiditis. But the rare evenience of this thyroidal
      affection made the diagnosis very improbable and the patient was treated by
      partial exeresis of the cervical mass and drainage of its apparently suppurative
      content. At the pathologic study the mass revealed its true nature, also if very
      unusual: the appearance of the specimen, studied also with immuno-chemical
      methods, revealed its true nature of scleronodular Hodgkin disease probably born
      on a thymic cyst remnant. Also the possibility of a suppurative evolution from a
      pyriform laryngeal sinus is discussed, but simply on a differential diagnostic
      basis for the original hypothesis of an inflammatory mass. The correct diagnosis
      instead offered the patient the possibility of the correct chemo-radio
      therapeutic treatment and of final cure.

PMID- 8154669
TI  - Introduction. Method and theory in the classification of alcoholics.

PMID- 8154670
TI  - Assortment for the liability to substance abuse and personality traits.

PMID- 8154671
TI  - Second messenger and protein phosphorylation mechanisms underlying possible
      genetic vulnerability to alcoholism.

PMID- 8154672
TI  - Platelet MAO activity in type I and type II alcoholism.
AB  - Lowered activity of the enzyme MAOB in the platelets and other tissues of
      alcoholics than of nonalcoholics is the most replicated biological finding in
      genetic research in alcoholism. Data presented here and elsewhere also indicate
      that the relationship between MAOB activity and alcoholism extends to the
      clinical subtypes referred to as Type I and Type II alcoholism. A detailed
      examination of the relationship between in vitro platelet MAOB activity levels,
      alcoholic subtype, and general mental health status among the relatives of the
      probands suggests that low MAOB activity is a marker of increased risk overall
      and that the families of Type II alcoholics have a higher genetic risk loading
      than do the families of Type I alcoholics. This increased genetic loading is
      probably due to the classification of Type II alcoholics on the basis of features
      related to severity of illness and additional psychiatric features such as
      personality disorders. Although the families of alcoholics tend to have higher
      levels of psychiatric illness compared to the general population, the overall
      risk is compounded in the families of Type II alcoholics, and these differences
      in underlying risk are reflected in the observed differences in MAOB activities.
      Thus, MAOB is not a biological/genetic marker of alcoholism sensu stricto but is
      rather a biological/genetic marker of an underlying pathophysiologic process
      leading to alcoholism and other psychiatric illness. The task now before us is to
      understand this process and how the activity of MAOB is involved.

PMID- 8154673
TI  - Thyrotropin response to thyrotropin-releasing hormone in young men at high or low
      risk for alcoholism.

PMID- 8154674
TI  - Developmental evidence for at least two alcoholisms. I. Biopsychosocial variation
      among pathways into symptomatic difficulty.

PMID- 8154675
TI  - Environmental differences in young men with and without a family history of
      alcoholism.

PMID- 8154676
TI  - Coexisting problems and alcoholic family risk among adolescents.
AB  - A substantial subset of nonclinical adolescents reported single or multiple
      problems with regard to drinking behavior, depressive symptoms, and delinquency.
      Similar to previous research, boys reported higher levels of heavy and
      problematic drinking, whereas girls reported higher levels of depressive
      symptoms. Higher levels of alcohol involvement were associated with higher levels
      of delinquency for both boys and girls. Family history of alcoholism was
      associated with an overrepresentation of problem drinkers (as well as
      abstainers). These findings are fairly consistent with the adult alcohol typology
      literature in identifying coexisting problem patterns for the triumvirate of
      problem drinking, depressive symptoms, and antisocial behavior. Furthermore,
      these data support the manifestation of these patterns prior to the onset of
      alcohol dependence (and maybe alcohol abuse). Future longitudinal research needs
      to focus on the short- and long-term patterns of problem behaviors among
      adolescents and to identify common and unique precursors, correlates, and
      consequences associated with varying levels of alcohol involvement.

PMID- 8154677
TI  - Psychological expectancy as mediator of vulnerability to alcoholism.
AB  - Alcohol expectancy has proven to be a powerful predictor of drinking behavior,
      including alcoholism, in a wide range of groups. Three recent studies that begin
      to address expectancy's relation to other alcoholism vulnerability factors are
      reviewed. Results indicate that: (1) expectancies for reinforcement from alcohol
      predate teens' first drinking experiences; (2) expectancies predict subsequent
      drinking onset and problem drinking; (3) high initial expectancies lead to a
      vicious cycle of progressively more drinking and more positive expectancies
      during the adolescent years; (4) expectancy mediates the influence of family
      drinking history on adolescent drinking; and (5) as an alcohol-specific risk
      factor, expectancy adds to and (in women) interacts with more general,
      dispositional (personality) risk factors to predict problem drinking in young
      adults. These findings support the model of expectancy as a mediator of the
      original causal influences of earlier learning experiences.

PMID- 8154678
TI  - Heterogeneity of adolescent alcoholism.
AB  - Adolescent alcoholics in treatment were classified into two broad clusters. The
      larger group consisted of youth who demonstrated behavioral dyscontrol and
      hypophoria, whereas the smaller group consisted of individuals with primarily
      negative affect. These two clusters differed with respect to age of first drug
      use, age of first substance abuse diagnosis, severity of substance use, behavior
      disturbance, and psychiatric disorder. Difficult temperament loaded on the
      negative affect factor. In a second study, it was observed that difficult
      childhood temperament led to a number of different first diagnoses in the
      adolescents. No specific psychiatric outcome followed a difficult temperament.
      These results illustrate the heterogeneity of the adolescent alcoholic population
      and suggest that there are many developmental pathways to this outcome where a
      predisposing risk factor is a difficult temperament makeup.

PMID- 8154679
TI  - Anxiety and conduct disorders in early onset alcoholism.

PMID- 8154680
TI  - Alcohol and drug abusers subtyped by antisocial personality and primary or
      secondary depressive disorder.
AB  - Our data show that when substance abusers are subtyped simultaneously by
      antisocial personality disorder and the onset of depression relative to alcohol
      or drug abuse, groups of people with unique personality and affective profiles
      are identified. The profiles are represented by measures of affect-related
      personality variables such as trait anxiety, trait depression, histrionic traits,
      sensation seeking, and novelty seeking. These measures were chosen in an attempt
      to show that a "low arousal" personality type may be associated with antisocial
      personality and may thus indirectly be linked to a certain type (i.e.,
      ASP/nondepressed) of substance abuser. By using a multi-symptomatic typological
      schema (i.e., a constellation of diagnostic categories rather than just one), we
      can show that different personality or affective profiles are indeed associated
      with certain subtypes of substance abusers and that depressed people who use
      drugs or alcohol are different affectively from antisocial types. We also show
      that the relationship between "low" and "high" arousal personality profile and
      subtypes based on co-morbid psychopathology is highlighted even more when we take
      into account the onset of dysthymia or depression that is primary versus
      secondary to substance abuse. Our findings are in accord with others'
      descriptions of the "affective arousal" dimensions of personality and are the
      first to link these dimensions with subtypes based on ASP and depression.

PMID- 8154682
TI  - Research opportunities in typology and genetics of alcoholism.

PMID- 8154681
TI  - Familial alcoholism and personality-environment fit. A developmental study of
      risk in adolescents.

PMID- 8154683
TI  - Matching alcoholics to coping skills or interactional therapies. Role of
      intervening variables.

PMID- 8154684
TI  - The type A/type B distinction. Subtyping alcoholics according to indicators of
      vulnerability and severity.
AB  - Multidimensional typologies of alcoholics are reviewed, including Cloninger's
      neurobiological learning model, Morey and Skinner's hybrid model, and Zucker's
      developmental model. The more recent Type A/Type B typology proposed by Babor and
      colleagues is reviewed in more depth, as is a previous replication and extension
      by Litt and colleagues. Both the original study and the replication indicate this
      typology is a useful tool in classifying alcoholic inpatients into two groups and
      in matching alcoholics to the most suitable treatment. The present study
      replicates the typology using outpatient samples of male alcoholics. The
      resulting two clusters are very similar to those identified by the two earlier
      studies. As expected, the relative proportion of Type A alcoholics is higher in
      the outpatient samples than in the previously studied inpatient samples.
      Preliminary analysis of the typology's clinical efficiency suggests that the
      variables used to classify subjects might be appreciably reduced, thus effecting
      a considerable time savings in assessment. A discriminant function analysis
      indicates that using only 5 of the original 16 clustering variables results in a
      correct classification rate of almost 95%. Future research directions are
      addressed.

PMID- 8154685
TI  - Implications of typologies for treatment. A planner's perspective.

PMID- 8154686
TI  - Toward a comprehensive theory of alcoholism.

PMID- 8154687
TI  - Sex, gender, and alcoholic typologies.

PMID- 8154688
TI  - Components of antisocial personality disorder among women convicted for drunken
      driving.
AB  - For women, the temporal relationship between Antisocial Personality Disorder
      (ASPD) and alcoholism is unclear. Driving while intoxicated is both a symptom of
      ASPD and the alcohol-related problem most typically reported by women.
      Accordingly, a period prevalence sample of 33 women incarcerated for drunken
      driving offenses was assessed with the SCID to identify other symptoms of ASPD.
      Excluding behaviors that only occurred while drinking, only 1 of the 33 women met
      DSM-III-R criteria for ASPD. When behaviors while drinking were included, 18.2%
      (n = 7) met criteria for ASPD by having both a history of childhood conduct
      disorder and characteristic ASPD behaviors as adults. However, 57.6% of the
      sample displayed the pattern of adult behavioral symptoms without a history of
      childhood conduct disorder (n = 19). Women with a history of conduct disorder and
      ASPD had a younger mean age of onset of alcohol dependence (16.8 vs 25.6 years)
      and a higher rate of concurrent borderline personality disorder (85.7 vs 42.1%)
      than did women who had only adult symptoms of ASPD, but a similar rate of
      reported parental alcoholism (71.4 vs 72.2%). With one exception, women who were
      diagnosed with full ASPD with childhood conduct disorder (n = 6) had been truant
      and had run away from home, but none reported cruelty to animals, vandalism, or
      arson in childhood. Thus, behaviors diagnostic of ASPD were largely consequent to
      substance abuse, and childhood behaviors were limited predictors of ASPD.
      Relationships among gender, prodromal behaviors, and substance abuse appear more
      complex than anticipated, and they indicate the need to recognize adult onset
      ASPD associated with substance abuse as a legitimate diagnosis manifested
      differently by women and men.

PMID- 8154689
TI  - Evidence of heterogeneity of genetic effect in Iowa adoption studies.
AB  - This paper describes male adoption studies at the University of Iowa using
      private and public adoption agencies within the state of Iowa from 1974 to the
      present time. This research involves four large studies, the first two of which
      demonstrated significant genetic as well as environmental effects in the etiology
      of alcoholism as well as significant correlations between adoptee conditions of
      antisocial personality and alcohol abuse. Findings in the first two studies were
      similar. However, the third study, using a sample from Catholic-sponsored
      adoption agencies across the state, failed to show a genetic effect. The final
      and fourth study was designed in part to look for heterogeneity in the
      manifestation of a genetic factor from one sample to another in the Iowa studies.
      This was done by sampling from two agencies, one of which had shown a genetic
      effect and the other that had not. In this fourth study, the agency that had not
      shown a genetic effect in the previous study also failed to show an effect, but
      the agency that had shown a significant genetic effect in the past did
      demonstrate a significant genetic effect. There were two remaining agencies in
      the fourth study for which no comparison with past samples could be made. One of
      these agencies showed a marginally significant genetic effect and the other
      showed no effect. Statistical analysis of this last study suggested that observed
      variability in the odds ratio from sample to sample was due to differences in
      manifestation of the genetic effect.

PMID- 8154690
TI  - Personality-based subtypes of chemically dependent patients.
AB  - Jackson's Personality Research Form E (PRF) was administered to a large,
      heterogeneous group of adult inpatients with diagnoses of alcohol and/or drug
      dependence. Cluster analysis of PRF factor scores yielded five distinct patient
      subtypes: hostile-dependent, cooperative-nonreflective, socially uninvolved,
      impulsive-unsociable, and hostile-overcontrolled. The subtypes differed on two
      MMPI canonical variables and on self-reported high risk factors for substance
      usage. Implications of the findings for more appropriate matching of patients to
      chemical dependency interventions are offered.

PMID- 8154691
TI  - Genetic influences on alcohol consumption patterns and problem drinking: results
      from the Australian NH&MRC twin panel follow-up survey.
AB  - Self-report questionnaire data from 3,000 adult twin pairs participating in the
      1988-1989 follow-up survey of the Australian NH&MRC twin panel were analyzed to
      determine (1) the contribution of genetic factors to risk of problem drinking in
      males and females; and (2) the magnitude of the correlation between genetic
      effects on problem drinking and genetic effects on alcohol consumption level.
      Significant genetic contributions were found both for average weekly consumption
      of alcohol and for problem-drinking history. For level of consumption, genetic
      factors accounted for approximately 58% of the variation in females and 45% of
      the variation in males. Heritability estimates for problem drinking, though
      significantly greater than zero, were variable in magnitude, ranging (under
      different models) from 8-44% in females and 10-50% in males. Likewise, estimates
      of the magnitude of the genetic correlation, whilst in all cases significantly
      greater than zero, ranged from 0.42-1.00 in females and 0.45-1.00 in males under
      different models.

PMID- 8154692
TI  - Variants of alcoholism: patterns in development, course, and prognosis.

PMID- 8154693
TI  - Thirty-year follow-up of men at high risk for alcoholism.

PMID- 8154694
TI  - Introduction: what is human reproductive ecology, and why should we care about
      studying it?

PMID- 8154695
TI  - Maternal nutrition and reproduction: why demographers and physiologists disagree
      about a fundamental relationship.

PMID- 8154696
TI  - Implications of hormonal influences on sexual behavior for demographic models of
      reproduction.
AB  - In exploring the implications of hormonal influences on sexual behavior for
      reproduction, we have focused on androgens because of the convincing evidence for
      androgenic effects on female sexual motivation. We have been guided by the simple
      idea, based on clinical findings among hyperandrogenic women, that higher
      testosterone levels will increase female sexual motivation which in turn will
      result in increased coital frequency. However, careful consideration of the
      evidence fails to confirm such a role for testosterone in sexual behavior among
      normal women at any point in the reproductive span. While some amount of
      testosterone appears to be important in maintaining female sexual motivation,
      there is little evidence that variation in testosterone within the normal range
      is associated with variation in sexual motivation. Reported associations between
      testosterone and sexual behavior among married women cannot be interpreted as
      resulting from androgenic effects on sexual motivation. Thus we are left with the
      task of explaining why testosterone does not appear to play the same role in
      libido among hyperandrogenic and normal women. As mentioned earlier, some of the
      difference may attributable to the much higher levels of testosterone among
      hyperandrogenic women. Sherwin points out that the levels of sexual motivation
      decline with declining testosterone levels even while testosterone is well above
      normally occurring levels. It is possible that the brain is simply not sensitive
      to the variation in testosterone levels found in normal women. Other evidence
      suggests that the presence of intact ovaries may be equally important. A recent
      study of androgen replacement in naturally post-menopausal women failed to find a
      dramatic effect of testosterone on sexual motivation and behavior, despite levels
      similar to those in studies on surgically menopausal women, pointing to the
      importance of other factors associated with the presence of ovaries. A similar
      point can be made with regard to hyperandrogenism related to endogenous sources
      of testosterone, as in the case of PCOS. High levels of testosterone effectively
      disrupt ovarian function and interfere with other ovarian processes. Among
      hyperandrogenic women sexual behavior appears to be related to the direct effects
      of androgens on motivation, while the indirect effects of estrogen and
      progesterone are essentially eliminated. Among normal women, on the other hand,
      there is little evidence for such a dominating role of a direct androgenic effect
      on sexual behavior. Instead, other ovarian hormones, including estrogen and
      progesterone may also play a demonstrable role, despite the lack of strong
      evidence at this point.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8154697
TI  - Behavioral and biological determinants of fecundability.
AB  - Our discussion has focused on a set of behavioral and physiological factors which
      influence fecundability. Some potentially important determinants are notable
      primarily because of their absence. Foremost among these determinants (as a
      group) are the male attributes. We have, by and large, ignored the links between
      male sexual behavior and hormonal profiles and the effects of hormones (or other
      factors) on sperm function. The fact that we have not reviewed them here does not
      imply that we believe that they are unimportant. Indeed, the effects of male
      factors may be particularly important because in some settings men are the
      predominant, if not the sole, decision-makers regarding reproductive behaviors
      including initiation of sexual intercourse and use of contraception. Also
      conspicuous by their absence are the effects of nutrition, consumption of
      alcohol, exercise, smoking, and behavioral and hormonal correlates of stress, all
      of which may affect fecundability. We have, though, reviewed a wide range of
      factors which contribute to fecundability and identified several points of
      potential interaction between the behavioral and biological determinants. We
      expect that our future understanding of these processes will be enhanced by
      empirical work and modeling efforts which also interact to draw upon the insights
      provided by each.

PMID- 8154698
TI  - Physiological mechanisms underlying lactational amenorrhea.
AB  - Breastfeeding delays the resumption of normal ovarian cycles by disrupting the
      pattern of pulsatile release of GnRH from the hypothalamus and hence LH from the
      pituitary. The plasma concentrations of FSH during lactation are sufficient to
      induce follicle growth, but the inadequate pulsatile LH signal results in a
      reduced estradiol production by these follicles. When follicle growth and
      estradiol secretion does increase to normal, the suckling stimulus prevents the
      generation of a normal preovulatory LH surge and follicles either fail to
      rupture, or become atretic or cystic. Only when the suckling stimulus declines
      sufficiently to allow generation of a normal preovulatory LH surge to occur will
      ovulation take place with the formation of a corpus luteum of variable normality.
      Thus suckling delays the resumption of normal ovarian cyclicity by disrupting but
      not totally inhibiting, the normal pattern of release of GnRH by the
      hypothalamus. The mechanism of suckling-induced disruption of GnRH release
      remains unknown. It does not appear to involve prolactin, dopamine or opiates
      although a combination of these factors might be involved. Prolactin is the major
      hormone responsible for milk production and is present in sufficient quantities
      in almost all women to allow the establishment of normal lactation. Oxytocin is
      essential for milk let down and is susceptible to inhibition of release by
      stress. The successful initiation of lactation which would lead to the potential
      of utilizing breastfeeding as contraceptive may require more attention to be paid
      to the establishment of non-stress release of oxytocin.

PMID- 8154699
TI  - Selection bias associated with contraceptive practice in time-to-pregnancy
      studies.
AB  - In studies of subfertility using data on time to pregnancy (the number of
      noncontracepting menstrual cycles required to conceive), many pregnancies are not
      included in analyses because time-to-pregnancy data cannot always be collected.
      Birth control failures are one such group (couples who are using birth control
      regularly or sporadically, but become pregnant anyway). The more fecund couples
      are more likely to have birth control failures, and consequently, more likely to
      be excluded from analyses. If an exposure of interest is associated with
      irregular use of birth control or with the choice of less effective methods of
      birth control, the fecundability in the exposed (based on data from couples who
      can provide adequate time to pregnancy data) will be underestimated. Such bias
      may account for the findings in the literature showing reduced fecundability
      among smokers. More generally, when a subset of couples who differ in their
      fecundability are excluded from analysis, there will be opportunity for selection
      bias to produce under or overestimation of the strength of an association between
      an exposure and fecundability. This problem affects both retrospective and
      prospective studies. Time-to-pregnancy studies need to be designed to minimize
      this potential bias and to collect data to evaluate it adequately.

PMID- 8154700
TI  - Epidemiologic studies of male factors in infertility.

PMID- 8154701
TI  - Pelvic inflammatory disease and tubal infertility: the preventable conditions.

PMID- 8154702
TI  - Seasonality of menarche among U.S. females: correlates and linkages.

PMID- 8154703
TI  - Seasonal effect on pregnancy loss rates in humans.

PMID- 8154704
TI  - The effects of season on female fertility as measured by the outcome of frozen
      thawed donor inseminations.

PMID- 8154705
TI  - Ranging hormones: do hormonal contraceptives ignore human biological variation
      and evolution?

PMID- 8154706
TI  - Effects of creatinine correction to urinary LH levels on the timing of the LH
      peak and the distribution of coitus within the human menstrual cycle.

PMID- 8154707
TI  - Hormonal and ecological contributions toward interpersonal intimacy in couples.

PMID- 8154708
TI  - Psychological stress and lipoperoxidation in miscarriage.

PMID- 8154709
TI  - The common marmoset as a model for nutritional impacts upon reproduction.

PMID- 8154710
TI  - The effects of calories and types of supplements on postpartum amenorrhea in the
      Philippines.

PMID- 8154711
TI  - Reproductive function in nomadic and settled women of Turkana, Kenya.

PMID- 8154712
TI  - Causes and consequences of heterogeneity in infant feeding practices among
      indigenous Andean women.

PMID- 8154713
TI  - Secondary sex ratios and patterns of sexual behavior: a test of James'
      proposition.

PMID- 8154714
TI  - Investigating the determinants of postpartum amenorrhea using a multistate
      hazards model approach.

PMID- 8154715
TI  - Socioeconomic mediation of birth interval duration in a Papua New Guinea
      population.

PMID- 8154716
TI  - Seasonality of workloads and ovarian function in Nepali women.

PMID- 8154717
TI  - Child nutrition, birth spacing, and child mortality.
AB  - Over half of all deaths in young children are caused by acute respiratory
      infections and diarrhea. Interventions have been targeted to treatment of
      illness, not prevention. Mortality levels have declined in response, but
      morbidity levels remain high. Declines in mortality have stagnated in many areas.
      High rates of child malnutrition are a major reason for continued morbidity and
      mortality from such illnesses. Case fatalities and severity of illness due to
      diarrhea and pneumonia are greatest in malnourished children. Improvement in
      feeding of young children is associated with lower incidence or severity of these
      and other illnesses. Efforts to improve young child feeding need to be integrated
      into child survival activities. Increasing durations of exclusive breastfeeding
      (to six months) and improving complementary feeding will promote child growth and
      reduce infection and mortality. These interventions are likely to enhance child
      spacing.

PMID- 8154718
TI  - Estimating the incidence and prevalence and analyzing the correlates of
      infertility and sterility.

PMID- 8154719
TI  - Statistical issues in the analysis of reproductive histories using hazard models.

PMID- 8154720
TI  - Bias in retrospective studies of spontaneous abortion based on the outcome of the
      most recent pregnancy.
AB  - In a retrospective studies of spontaneous abortion, bias can arise if the
      investigator restricts attention to the outcome of the most recent pregnancy.
      Bias happens because couples tend to replace spontaneous abortions with other
      pregnancies until they achieve a live birth, after which they may avoid
      conception for a long time. Consequently, the proportion of most recent
      conceptions ending in loss might be very low compared to what would be seen in a
      prospective study. Also, time since conception is negatively correlated with
      apparent risk, because most pregnancies which occurred relatively long ago and
      ended in loss have been replaced by subsequent pregnancies. If the exposure of
      interest may also have changed over time, then time since conception should be
      considered a potential confounder. In addition, the consistency with which
      couples use birth control varies. Some couples are planners who use effective
      contraception and plan the growth of their family with deliberation; others have
      most of their pregnancies unintentionally. As a result, the most recent pregnancy
      is less likely to be a spontaneous abortion for a planner than for a nonplanner.
      If planners and nonplanners also differ in their exposures, then bias will
      result. Other factors which affect the interpregnancy interval, such as
      fecundability, breastfeeding, and desired family size can distort the relative
      sampling fraction for spontaneous abortions compared to live births and, to the
      extent that such factors are associated with the exposure, can bias estimates of
      relative risks.

PMID- 8154721
TI  - Salivary steroids and natural variation in human ovarian function.

PMID- 8154722
TI  - Male factors contributing to the seasonality of human reproduction.

PMID- 8154723
TI  - The use of urinary hormonal assessments in human studies.
AB  - The collection and analysis of urine samples provides a practical method for
      monitoring female reproductive events in non-laboratory and non-clinic
      populations. Collection of biologic samples permits objective assessment of
      reproductive health endpoints in epidemiologic studies and for epidemiologic
      research purposes can provide validation of information provided by the subjects,
      especially outcomes which are usually concealed and thus unknown to the
      participant. Urine sampling has several advantages over the collection of blood
      samples, such as simplicity, non-invasiveness, and cost efficiency. Several
      studies have shown that endocrine information similar to that obtained in blood
      samples can be obtained from assays of daily urine samples. The measurement of
      human chorionic gonadotropin in daily and selected urine samples has been
      incorporated into several recent epidemiologic studies focusing on early fetal
      loss, and ovarian and pituitary hormone metabolites have been measured in daily
      urine samples to evaluate ovarian function in studies focusing on women's
      reproductive health. As the strategy of urinary monitoring becomes more accepted
      as a legitimate research tool, laboratory methods are being modified to improve
      performance, reduce costs and adapted to sophisticated algorithms using multiple
      hormonal measurements to identify a number of end-points.

PMID- 8154724
TI  - Blood, urine, saliva and dip-sticks: experiences in Africa, New Guinea, and
      Boston.

PMID- 8154725
TI  - Influence of human reproduction on environment. What features of biology and
      economics cause them to see population differently?
AB  - Disciplinary isolation: like species with common descent, between whom a barrier
      has arisen, the disciplines have evolved independently. Each discipline evolves
      on its own dynamic. We are not concerned with opinions of eccentric individual
      scholars, but with the mainstreams, in particular of biology and economics that
      today strongly disagree. The disciplines have changed sides. Biology and
      economics disagreed also in the 19th century, but then biologists were optimists,
      economists pessimists, on the population-holding capacity of the Earth. Words are
      used differently in different disciplines, and that arises from and maintains
      different styles of thought, so that language is one of the barriers between
      disciplines. A serious matter when "data do not support family planning" is taken
      as an argument against family planning. Failure to support the hypothesis being
      tested by no means proves the hypothesis; it is as likely to show merely that the
      data are inadequate.

PMID- 8154726
TI  - Funding considerations in human reproductive ecology: summary of an evening panel
      discussion on sources and resources.

PMID- 8154728
TI  - Understanding seasonality in Bangladesh.

PMID- 8154727
TI  - Rapid population growth and fragile environments: the sub-Saharan African and
      south Asian experience.

PMID- 8154729
TI  - The start of the sub-Saharan fertility transitions: some answers and many
      questions.

PMID- 8154730
TI  - Human fertility and population equilibrium.
AB  - In preindustrial settings, biological, economic, and social mechanisms caused
      fertility to respond to feedback signals from population size variation in such a
      way as to steer populations toward equilibrium levels. It is unlikely that the
      relevant signal was population density; more plausibly the signal was economic
      well being, which in turn responded to population density, among other
      influences. Numerous empirical studies provide persuasive evidence for such a
      fertility response. However, the response was relatively weak, so that
      populations responded only slowly to shocks. The half life of a shock-induced
      deviation from equilibrium was probably on the order of 70 years. Dynamic
      behavior of population size was discernibly affected only in the long run.
      Because of the presence of environmental external costs to childbearing, and
      because fertility response mechanisms were not necessarily intentional, the
      equilibrium population size and corresponding welfare need not have possessed any
      desirable properties. In developed countries, these equilibrating mechanisms are
      no longer in effect.

PMID- 8154731
TI  - Why can't demographers and physiologists agree? Issues of study design.

PMID- 8154732
TI  - Human reproduction in an evolutionary context.

PMID- 8154733
TI  - Human reproductive ecology: conference summary.

PMID- 8154734
TI  - Seasonal differences in pregnancy outcomes: United States, 1971-1989.

PMID- 8154735
TI  - Physical activity, nutrition, and reproduction.

PMID- 8154736
TI  - Lactation and other metabolic loads affecting human reproduction.

PMID- 8154737
TI  - Determinants of adolescent fertility and its consequences for maternal health,
      with special reference to rural Bangladesh.
AB  - The second section of this paper set forth a theoretical model relating
      adolescent growth and development to family formation patterns and their
      implications for maternal and child health. Subsequent sections of the paper
      examine the evidence to support specific relationships hypothesized in the model,
      focusing on longitudinal data from Matlab, Bangladesh. Despite the emphasis on
      developing country populations, literature from developed countries was also
      reviewed. The weight of the evidence suggests that in the developed countries,
      while there is a positive relationship between reproductive maturation and
      subsequent reproductive behavior, the negative effects of young maternal age on
      pregnancy outcome is confounded with socioeconomic factors. Teenage pregnancy, or
      at least teenage birth, occurs disproportionately among the socially and
      economically disadvantaged. Moreover, teenage childbearing in the U.S.,
      especially when it occurs outside of marriage, violates social norms, at least in
      the white population. Poor diet may be a problem in the U.S. but it does not
      appear to result in notable delays in physical growth and development, delayed or
      compromised adolescent growth, or late age at menarche. Limited evidence suggests
      that early menarche may be associated with more rapid onset of mature menstrual
      cycle activity but these findings have not been replicated elsewhere. In
      developing countries the situation is quite different. First, early marriage and
      childbearing are desired and common across most segments of society. Second,
      malnutrition is widespread, and is sufficiently severe to delay the adolescent
      growth spurt and raise average age at menarche by two to three years compared
      with developed country populations. This is certainly the case in Bangladesh. In
      this setting, several observations regarding the relationship of nutritional
      status, adolescent development and reproduction have been made. First,
      undernutrition delays growth and reproductive maturation, and women who mature
      early (i.e., women with young age at menarche) marry at younger ages than later
      maturers. In addition, body weight appears to have an independent effect on age
      at marriage, net of age at menarche, such that relatively heavy women marry at
      younger ages than their lighter counterparts. Explanations for this finding
      include correlation between body weight and development of secondary sex
      characteristics, and perhaps a cultural perception that heavier (i.e., normal
      body weight) women are more attractive, or healthier, mates. The effect of
      menarche and nutritional status on marriage gives rise to concern that an
      improvement in nutritional status, and an increase in the age at menarche, would
      lead to younger marriage and first birth, and higher lifetime fertility.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8154738
TI  - Global patterns of seasonal variation in human fertility.
AB  - Pronounced and persistent seasonal patterns in fertility are observed in
      virtually all human populations. This paper presents evidence on these seasonal
      patterns. We note that the most pronounced seasonal patterns are in the southern
      United States, where births decline substantially in April and May, and in
      northern Europe, where births increase substantially in March and April. Although
      seasonal variations in fertility were more pronounced in earlier agricultural
      populations, we show that seasonality has increased in this century in some high
      income, low fertility populations such as Sweden. We use data on monthly
      temperature to analyze the potential role of temperature in explaining seasonal
      patterns. We find strong evidence that summer heat plays an important role in
      explaining the July-August trough in conceptions in the southern United States.
      We find little evidence, however, that temperature plays any role in explaining
      the pronounced June-July peak in conceptions in Sweden. Temperature also appears
      to be relatively unimportant in several other populations with substantial
      seasonal variations in births, suggesting that other factors play an important
      role in birth seasonality.

PMID- 8154739
TI  - Potassium channel toxins and transmitter release.

PMID- 8154740
TI  - Effects of toxins on Ca2+ currents and peptide release from nerve terminals.

PMID- 8154741
TI  - Presynaptically acting phospholipase A2 from Vipera ammodytes venom.

PMID- 8154742
TI  - Rattlesnake toxins alter development of muscle cells in culture.

PMID- 8154743
TI  - Different evolution of phospholipase A2 neurotoxins (beta-neurotoxins) from
      Elapidae and Viperidae snakes.

PMID- 8154744
TI  - Exocytosis of toxins in amphibians and fishes.

PMID- 8154745
TI  - Protein toxins that bind to muscarinic acetylcholine receptors.

PMID- 8154746
TI  - On the role of the elastic properties of closed lamellar membranes in membrane
      fusion.

PMID- 8154747
TI  - Study of rab6, a ras-like GTP-binding protein associated with the Golgi complex.

PMID- 8154748
TI  - Synthetic peptides to mimic the role of GTP binding proteins in membrane traffic
      and fusion.

PMID- 8154749
TI  - Endocytosis: aspects of organellar processing.

PMID- 8154750
TI  - The exocytotic reaction of permeabilized rat mast cells. An all-or-none response.

PMID- 8154751
TI  - Three distinct fusion processes during eosinophil degranulation.

PMID- 8154752
TI  - Exocytosis in sea urchin eggs.

PMID- 8154753
TI  - Control of exocytosis in a plant secretory cell by cytosolic Ca2+ and hydrostatic
      pressure.

PMID- 8154754
TI  - Calcium oscillations and exocytosis in pituitary gonadotropes.

PMID- 8154755
TI  - Integrin-dependent mobilization of intracellular calcium ions in osteoclasts. A
      possible role in the regulation of the secretion of protons and lysosomal
      enzymes.

PMID- 8154756
TI  - New approaches in the study of stimulus-secretion coupling in anterior pituitary
      cells.

PMID- 8154757
TI  - Increased cytosolic chloride affects depolarization-induced changes in membrane
      capacitance and cytosolic calcium activity in rat melanotrophs.

PMID- 8154758
TI  - Identification of proteins required for Ca(2+)-activated secretion.

PMID- 8154759
TI  - Characterization of proteins that regulate calcium-dependent exocytosis in
      adrenal chromaffin cells.

PMID- 8154760
TI  - Protein phosphorylation and the control of exocytosis in neurons.

PMID- 8154761
TI  - Effects of arsenicals on the secretory process in chromaffin cells.

PMID- 8154762
TI  - A tissue-specific protein of the venom gland of black widow spider affects alpha
      latrotoxin action.

PMID- 8154763
TI  - Botulinum toxin in the treatment of neurological disorders.
AB  - Botulinum toxin therapy is safe and effective in the treatment of different
      movement disorders, especially focal dystonias. We reviewed botulinum toxin
      treatment of 97 patients: 36 had blepharospasm, 41 had torticollis, and 20 had
      diverse movement disorders. Patients with blepharospasm and torticollis improved
      markedly after botulinum toxin injections. The most common side effect in BS
      patients was ptosis (44.4%); in TC patients, it was dysphagia (29.3%). The mean
      duration of the improvement in both groups was 3.4 months. Very promising results
      were obtained also in the heterogeneous group including patients with other focal
      dystonias and cerebral palsy. On the basis of these results, we concluded that
      BTA injections must now be considered the mainstay of therapy for focal dystonias
      and other involuntary movement disorders.

PMID- 8154764
TI  - Chronic denervation caused by botulinum neurotoxin as a model of a neuromuscular
      disease.

PMID- 8154765
TI  - Tetanus toxin and Clostridium perfringens enterotoxin as tools for the study of
      exocytosis.
AB  - The role of calmodulin in exocytotic secretion was studied using digitonin
      permeabilized bovine adrenal chromaffin cells to examine the effect of calmodulin
      directly introduced into the cells and using tetanus toxin as a specific
      inhibitor of exocytotic secretion. Addition of calmodulin to the permeabilized
      cells increased Ca(2+)-dependent norepinephrine release in a dose-dependent
      manner. The enhancement of release by calmodulin was specific to calmodulin:
      bovine serum albumin, actin, and caldesmon had no such effect. Enhancement of
      release by calmodulin occurred at Ca2+ concentrations of more than 10(-6) M and
      increased with an increase of Mg2+ concentration. The release of norepinephrine
      enhanced by calmodulin was inhibited by tetanus toxin. These results indicate
      directly that calmodulin plays an important role in exocytotic secretion from
      chromaffin cells. Exocytosis is known to occur by fusion of plasma membrane with
      limiting membranes of secretory vesicles following an increase in intracellular
      Ca2+. We used the enterotoxin of Clostridium perfringens type A as a specific
      tool to modify plasma membrane permeability to induce calcium influx.
      Multigranular exocytosis was recognized electron-microscopically in addition to
      the single-granular exocytosis in rat anterior pituitary cells and pancreatic
      acinar cells treated with the enterotoxin in the presence of extracellular Ca2+.
      The treatment with the enterotoxin did not induce any drastic change in the fine
      membrane structures of both types of cells. The enterotoxin-treated anterior
      pituitary cells and pancreatic acinar cells should provide a useful system for
      studying the molecular mechanism of fusion of membranes in exocytosis.

PMID- 8154766
TI  - Chronic stenosis of the larynx with special consideration of skin grafting. 1940.
AB  - 1. Treatment for chronic stenosis of the larynx should be delayed until the
      patient is in the best possible general condition and until any local
      inflammatory reaction has entirely cleared. 2. The type of treatment indicated in
      a given instance depends largely on the character and extent of the stenosis
      rather than on its cause. 3. Bouginage, the most commonly employed procedure in
      the treatment of stenosis of the larynx, has in our experience at The Mayo Clinic
      been one of the least effective procedures. 4. Elastic pressure applied by means
      of soft rubber dilators is one of the most satisfactory methods of treating
      chronic stenosis. 5. Laryngofissure with excision of the scarring and any
      thickened or distorted cartilage, followed by skin grafting, is the most
      effective method of dealing with chronic cicatricial stenosis and often will
      restore a satisfactory laryngeal lumen after other methods of treatment have
      failed.

PMID- 8154767
TI  - Three-dimensional motion of the arytenoid adduction procedure in cadaver
      larynges.
AB  - To determine whether variation in suture placement could improve the results of
      the arytenoid adduction procedure, a model was developed using fresh human
      cadaver larynges. Three-dimensional (3-D) motion of the arytenoid was determined
      by utilizing computed tomographic imaging with radiopaque markers on the apex and
      muscular and vocal processes. By utilizing principles previously applied to the
      study of rigid body mechanics for the carpal, knee, and tarsal joints, rotation
      and translation of the arytenoid about the axial, coronal, and sagittal axes were
      calculated. Subglottic airflow resistance was measured before and after the
      procedure. Posterior glottic closure was reproducibly achieved, as determined by
      computed tomographic imaging and airway resistance. Conflicting reports on
      cricoarytenoid joint mechanics can be attributed to reliance on trigonometric
      analysis of two-dimensional images, which results in errors in out-of-plane
      motion. This paper presents a useful model for obtaining detailed anatomic
      information describing arytenoid 3-D motion.

PMID- 8154768
TI  - Arytenoidectomy in children.
AB  - Vocal cord paralysis is the second most common cause of stridor in early infancy,
      and as many as 52% of patients will not recover spontaneously. Bilateral vocal
      cord paralysis often requires a tracheotomy for airway distress. If resolution of
      the bilateral vocal cord paralysis does not allow for decannulation,
      arytenoidectomy is an option. A retrospective review of 30 children with
      bilateral vocal cord paralysis who underwent an arytenoidectomy was undertaken.
      An external arytenoidectomy via laryngofissure was performed in 19 patients, a
      laser arytenoidectomy in 12 patients, and a Woodman procedure in 1 patient.
      Twenty-five of the 30 patients (83%) were decannulated. Decannulation was more
      likely after a laryngofissure (84%) than after a laser arytenoidectomy (56%). The
      probability of decannulation was related to the presence of concomitant
      conditions and the need for other airway procedures. While breathiness,
      hoarseness, and pitch change were common, all patients had an adequate voice
      postoperatively and demonstrated little change from the preoperative voice
      disturbance. Aspiration was a rare complication. After an adequate period of
      observation for spontaneous resolution, arytenoidectomy via external
      laryngofissure is recommended to aid in the decannulation of children with
      bilateral true vocal cord paralysis.

PMID- 8154769
TI  - Olfactory mucosa of patients with olfactory disturbance following head trauma.
AB  - The olfactory mucosa in 7 patients with olfactory disturbance following head
      trauma were sampled for biopsy with special biopsy forceps and examined by
      immunohistochemical staining with anti-neuron-specific enolase (NSE) and S-100
      protein (S-100) antibodies. The residual olfactory receptor cells and nerve
      bundles were counted, and the degree of degeneration was determined. In 5
      patients, olfactory receptor cells that reacted with anti-NSE antiserum remained,
      although the number varied with the patient, and in 2 patients the receptor cells
      disappeared. In the lamina propria, the S-100-immunoreactive olfactory nerves
      were retained in 6 patients. The outcome was poor in all cases regardless of the
      number of residual receptor cells and nerve bundles. These results indicate that
      the degree of impairment of the peripheral olfactory region after head trauma
      differs from case to case, and that even if the receptor cells and nerve bundles
      remain, it is difficult to improve the condition, although some cases of
      malingering may be contained.

PMID- 8154770
TI  - Results from four cochlear implant patients with Usher's syndrome.
AB  - Individual results are presented of 4 patients with Usher's syndrome type 1 who
      received a cochlear implant. Both single-channel and multichannel implants were
      used. Because of implant failure, one of the single-channel systems was replaced
      by a Nucleus multichannel system. Results are compared to the results of 5 other
      prelingually deaf cochlear implant users. The performance of the patients with
      Usher's syndrome on suprasegmental and segmental speech perception tests and on a
      connected discourse tracking task did not differ significantly from the
      performance of the other prelingually deaf patients. A significant improvement
      over time was found at the suprasegmental level for the combined group of Usher's
      and other patients. No obvious differences were found between the scores from the
      patients with a single-channel and the patients with a multichannel device. The
      rehabilitation of the Usher's patients required very little extra effort in
      comparison with that of the other prelingually deaf patients; all patients
      reported considerable advantages in hearing abilities and social life.

PMID- 8154771
TI  - Non-Hodgkin's lymphomas of the nose and paranasal sinuses in the pediatric
      population.
AB  - Paranasal and nasal neoplasms often elude early diagnosis in the pediatric
      population. This report examines 3 cases of nasal and paranasal sinus lymphomas
      out of 29 lymphomas and lymphoproliferative disorders seen from 1983 to 1990.
      Diagnostic delays are common. The development of orbital signs and symptoms often
      leads to diagnosis. Computed tomography and magnetic resonance imaging are
      important in delineating the extent of disease and allow appropriate staging.
      Transnasal biopsy yields the definitive diagnosis, with low associated morbidity.
      Aggressive chemotherapy and irradiation prolongs survival; with this regimen all
      of our patients have remained alive, although 1 has residual disease. B-cell
      lymphomas are more common than T-cell varieties in children. One patient
      demonstrated B-cell immunodeficiency and preleukemia prior to developing primary
      paranasal sinus non-Hodgkin's lymphoma; this case reiterates the systemic nature
      of lymphoma, Key differences between children and adults in the manifestations of
      nasal and sinus lymphomas are emphasized.

PMID- 8154772
TI  - Acyclovir in the treatment of recurrent respiratory papillomatosis. A pilot
      study.
AB  - Six patients with severe, recalcitrant, juvenile-onset recurrent respiratory
      papillomatosis were treated with 7 independent trials of acyclovir. In 2 trials,
      patients received acyclovir in place of interferon-alpha; the remaining 5 trials
      were in patients not otherwise receiving chemotherapy. Quantitative analysis of
      overall disease extent, laryngeal involvement, and degree of glottic obstruction
      for the 6 months prior to acyclovir administration and during acyclovir
      administration demonstrated a statistically significant decrease in all
      parameters evaluated in those patients who were otherwise unmediated. The 2
      patients who discontinued interferon-alpha immediately prior to beginning
      acyclovir demonstrated worsening disease, consistent with the well-recognized
      rebound phenomenon associated with stopping interferon. This study suggests that
      acyclovir decreases the extent of respiratory papillomatosis in patients with
      recalcitrant disease. The beneficial effect of acyclovir appears to be
      insufficient to counteract the rebound of disease when interferon is stopped
      abruptly.

PMID- 8154774
TI  - Localization of function in the eustachian tube: a hypothesis.
AB  - This communication uses our recent quantitative morphometric studies to develop a
      hypothesis for localization of ventilatory, clearance, and protective functions
      in different portions of the eustachian tube (ET). We hypothesize that the ET
      roof is involved mainly with ventilation and that the ET floor is involved mainly
      with clearance, whereas both portions are involved with protection of the middle
      ear. The hypothesis states that 1) the cross-sectional shape of the ET lumen and
      the attachment of the tensor veli palatini muscle to the tip of the lateral
      lamina are important for ventilation, 2) the ciliated cells in the ET floor
      subserve clearance, 3) the richly distributed elastin in the hinge portion of the
      ET cartilage, Ostmann's fatty tissue, and rich mucosa-associated lymphoid tissue
      are protective, 4) the well-developed ET cartilage lateral lamina is important
      for both ventilation and protection, and 5) the rich mucosal folding, goblet
      cells, and glands subserve both clearance and protection. Finally, the utility of
      the hypothesis for elucidating anatomic factors in otitis media is discussed.

PMID- 8154773
TI  - Rhinocerebral aspergillosis in patients undergoing bone marrow transplantation.
AB  - Rhinocerebral aspergillosis (RA) is becoming increasingly common in patients
      undergoing bone marrow transplantation (BMT). The disease can involve nearly all
      major head and neck structures, including the nose, paranasal sinuses, and
      orbits. Intracranial extension of the infection is of major concern, since this
      is usually a fatal complication. Our study population comprised 423 consecutive
      BMT patients at Hadassah University Hospital from January 1986 to August 1992.
      Eight patients (1.9%) developed RA, 5 of whom had underlying hematologic
      malignancies, and 3 of whom had severe aplastic anemia. Only 2 of the 8 patients
      responded completely to therapy, with a follow-up of 15 months. It appears that
      RA is a fatal complication in immunocompromised patients post-BMT. Early
      diagnosis followed by extensive surgical debridement of necrotic tissue and
      systemic, as well as topical, antifungal therapy with amphotericin B or its new
      formulations and the patient's recovery of bone marrow function may improve the
      outcome of this life-threatening complication.

PMID- 8154775
TI  - Primary liposarcoma of the larynx. Case report and literature review.
AB  - Laryngeal liposarcoma is an unusual tumor. Only 16 cases have been previously
      reported. We describe a new case of well-differentiated laryngeal liposarcoma and
      review the literature. The tumor was treated by surgical removal.
      Immunohistochemical study showed an immunophenotype consistent with liposarcoma.
      The case described is of the oldest patient (83 years old), the second to be
      found in a woman, and the second to be localized to one true vocal cord
      (according to the literature reviewed). The patient is still free of tumor 2
      years later. The treatment and prognosis of liposarcoma of the larynx are
      discussed.

PMID- 8154777
TI  - Technetium 99M(V) dimercaptosuccinic acid SPECT scintigraphy in head and neck
      tumors.

PMID- 8154776
TI  - Proposed grading system for subglottic stenosis based on endotracheal tube sizes.
AB  - The classification of airway stenoses has been a problem for many years. As a
      result, both intradepartmental and interdepartmental comparisons of airway sizes
      remain difficult. It follows that comparisons of therapeutic maneuvers are even
      more difficult. A system is proposed that is simple, reproducible, and based on a
      readily available reference standard. Endotracheal tubes, which are manufactured
      to high standards of precision and accuracy, can be used to determine the size of
      an obstructed airway at its smallest point. The endotracheal tube that will pass
      through the lumen, if one exists, and tolerate normal leak pressures (10 to 25 cm
      H2O), can be compared to the expected age-appropriate endotracheal tube size. By
      using the outside diameters of the endotracheal tubes, the maximum percentage of
      airway obstruction can be determined. We present a conversion of tube size to the
      proposed grading scale: grade I up to 50% obstruction, grade II from 51% to 70%,
      and grade III above 70% with any detectable lumen. An airway with no lumen is
      assigned to grade IV.

PMID- 8154778
TI  - Thyroid hemiagenesis.

PMID- 8154779
TI  - Extra-abdominal desmoid fibromatosis.
AB  - Desmoid fibromatosis cannot be considered a biologically benign or innocuous
      lesion. In the head and neck it may be intraosseous (desmoplastic fibroma) or,
      more often, in soft tissues, with the highest incidence in the supraclavicular
      region of the neck. High recurrence and persistence rates, 50% or more, accompany
      intralesional or marginal excision. Keloids and proliferative scars, while
      stubborn in their resolution and potentially disfiguring, are reactive
      proliferative disorders of fibroblastic and myofibroblastic tissues.

PMID- 8154780
TI  - Applied anatomy of the paranasal sinuses with emphasis on endoscopic surgery.
AB  - Serial sections of frozen cadaver heads were obtained in the axial, coronal, and
      sagittal planes. These were analyzed with specific attention to the anatomy of
      the paranasal sinuses as it pertains to endoscopic sinus surgery. Important
      anatomic landmarks are pointed out. The use of these landmarks to guide the
      surgeon through the dissection and to avoid complications is discussed. The
      resolution of chronic sinusitis is often brought about by the structural changes
      secondary to endoscopic sinus surgery, and the reasons for this outcome are
      reviewed.

PMID- 8154781
TI  - Falciparum malaria in naturally infected human patients: IV--Ultrastructural
      changes in peripheral white blood cells.
AB  - Ultrastructure of white blood cells (WBC) were studied in peripheral venous blood
      from Saudi patients with acute falciparum malaria (AFM) and compared with their
      counterparts in same patients 2 weeks after chloroquine treatment and full
      recovery. A counting system was incorporated to determine the rate of abnormal to
      normal cell type in plastic thick sections during the course of the disease.
      Neutrophilia, monocytosis, eosinopenia and lymphocytosis were associated with
      various ultrastructural abnormalities including: (1) Knobby phagocytic
      polymorphonuclear neutrophils (PMN) and promyelocytes, and PMN with highly
      vacuolated cytoplasm. (2) Irregularly outlined electron-dense nuclei in non
      functional monocytes. (3) Unusual distribution of nuclear chromatin in resting B
      lymphocytes, while others possess highly vacuolated cytoplasm and knobby
      surfaces. (4) Absence of granules in granular lymphocytes containing the known
      diagnostic paratubular crystalline arrays. (5) Plasmablasts containing electron
      dense granules and swollen mitochondria. These abnormalities were suggested to be
      due to the high level of parasitaemia producing some toxic soluble products. They
      may also be attributed to alteration of bone marrow macrophages as a sequence of
      their interaction with soluble parasite products or their phagocytic parasitized
      red cells and debris released during the rupture of schizonts. This study showed
      that the number of abnormal WBC increases in patients with high level of
      parasitaemia; plasmablasts have the lowest rate of abnormalities, while monocytes
      have the highest; old patients present with lower degree of parasitaemia than
      young patients due to a less mature immune system; and the AFM may have
      independent effects on the structure of human WBC.

PMID- 8154782
TI  - Onchocerca-like lesions induced by the filarioid nematode Cercopithifilaria
      johnstoni, in its natural hosts and in the laboratory rat.
AB  - Histo-pathological analysis of the eyes, ears, skin and associated skeletal
      muscles of the back of 14 animals infected with a filarioid worm with dermal
      microfilariae, Cercopithifilaria johnstoni: seven Rattus fuscipes, of which four
      were naturally infected, two marsupials, Perameles nasuta and Isodon macrourus,
      and five R. norvegicus. This filarioid nematode induces skin and eye lesions in
      all the infected animals. These lesions are similar to those described earlier
      with other filarioid species with dermal microfilariae, such as Monanema martini
      and Onchocerca volvulus; the pathogeny is similar: microfilariae live inside the
      lymphatic vessels and their accidental exit gives rise to a localized
      inflammatory reaction leading to fibrosis. C. johnstoni is particularly
      interesting because it may be adapted to the laboratory rat, and because the
      ocular lesions are severe.

PMID- 8154783
TI  - [Schizogony of Plasmodium yoelii nigeriensis. Role of latent merozoites].
AB  - Several procedures were employed to try to specify the schizogonic cycle of
      Plasmodium yoelii nigeriensis. The Percoll-glucose gradient technique for
      concentrating the very young stages (rings and young trophozoites), allowing a
      very precise follow up of the development of the parasitaemia during the first
      schizogonic cycles. A method for studying the prepatencies, providing an
      approximation of the number of merozoites inoculated. A comparison between the
      numbers of merozoites present in the blood, after--firstly simple dilutions in
      saline, revealing the total number of merozoites,--secondly dilutions in saline
      after a passage of a few hours in the organism of a mouse, revealing the number
      of latent merozoites. It was shown that the infection, during the first two
      cycles, varies according to the time of inoculation. In all cases the increase of
      the parasitaemia occurred mainly from 00:01 to 06:00. This increase of
      parasitaemia in mice inoculated with the Percoll concentrated parasites was
      significantly high during the first cycle in mice inoculated at 06:00 and 09:00
      and during the second cycle in those inoculated at 12:00, 15:00 and 18:00.
      However, differences were rapidly compensated and parasitaemias became comparable
      at the 3rd or 4th cycle when they ceased to be dependent on the time of
      inoculation.

PMID- 8154784
TI  - Plasmodium berghei: the use of discontinuous urografin density gradients for the
      separation of exoerythrocytic malaria parasites.
AB  - Urografin was used in the lower cushion of discontinuous density gradient
      systems, for the separation of human hepatoma cells (Hep G2) infected with
      exoerythrocytic P. berghei forms from uninfected cells. The hepatoma cells
      exhibited a rather heterogeneous density distribution, masking the possible
      density differences between infected and uninfected cells and hindering the
      efficient separation of both cell types. Purely osmotic damage caused by
      Urografin on human erythrocytes and hepatoma cells is very limited. On the other
      hand, the direct toxic effects on P. falciparum blood stages and on P. berghei
      exoerythrocytic stages are very pronounced. The growth of the former forms is
      partially inhibited after a pretreatment, but remains acceptable if the contact
      with Urografin is relatively short. It is almost completely blocked during
      permanent incubation. The latter forms are killed after 1 hour of contact with
      Urografin.

PMID- 8154785
TI  - Strianema venezuelensis gen. et sp. n. (Filarioidea: Onchocercidae) from
      Venezuelan armadillos (Dasypus spp.).
AB  - A new filaria, Strianema venezuelensis gen. et sp. n., is described from
      armadillos in Venezuela. The adults inhabit the subcutaneous tissues and the
      microfilariae are found in the skin and occasionally the blood. The adults, which
      are of small size (males 9.6 to 13.8 mm in length by 57 to 63 microns in
      diameter, females 18.3 to 26.3 mm in length by 95 to 120 microns in diameter),
      have a distinctly striated cuticle. This filaria resembles most closely the genus
      Cercopithifilaria, from which it can be distinguished by the absence of a buccal
      capsule or pre-esophageal ring, and 11 to 13 pair of caudal papillae, three or
      four pair of which are separated as a group anterior to the cloaca. The species,
      S. venezuelensis, can be distinguished from the three other species of filariae
      described from armadillos by the undivided esophagus, number and distribution of
      caudal papillae in the male, size and shape of the spicules, and the distinctive
      microfilaria. The microfilaria, which averages 280 microns in length, has a
      unique, slender, almost filamentous tail.

PMID- 8154786
TI  - [Comparison of PCR and cytogenetic methods for the identification of mosquito
      species of the Anopheles gambiae complex in Senegal].
AB  - The classical cytological technique and a new PCR technique were compared for the
      identification of mosquito species of the Anopheles gambiae complex. Fifty seven
      specimens, caught in three different bioclimatic senegalese regions, were tested.
      Thirty two An. gambiae and 25 An. arabiensis were determined by both methods. All
      the results were similar. The advantages of each method are discussed.

PMID- 8154787
TI  - [Study of combinations of antimicrobial agents. Development of the method].
AB  - We developed and validated a micromethod similar to the checkerboard method in
      antibiotherapy to study the efficiency of antiseptic and disinfectant molecules.
      The determination of the FBC index (Fractional Bactericidal Concentration) on 4
      reference strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus
      aureus, Enterococcus hirae) for 4 associations (2-benzyl-4 chlorophenol-
      iodophor; cetrimide-iodophor, 2 benzyl-4 chlorophenol--formaldehyde; hexamidine-
      formaldehyde) revealed 2 synergistic associations and 2 antagonistic associations
      for one or more strains.

PMID- 8154788
TI  - [Biocontamination, European standardization and pharmaceutical industry].
AB  - The coming to light of new concepts in environmental microbiology, particularly
      the notions of bacterial adhesion and of biofilm or of cells in starvation,
      conducted to an evolution of the standardization of the controlled contamination
      area. It is necessary to match to the biocontamination of hazard area the
      principles governing the quality insurance used in alimentary industry named
      HACCP (hazard analysis of control critical point). This method will have to be
      applied wilfully to all the fields where a patient or a product risk a
      biocontamination.

PMID- 8154789
TI  - [Evaluation of consumptions of alcoholic drinks during the National Service].
AB  - Using only ingested alcohol quantity, where individual erroneous values are
      counted and weigh a lot, alcohol consumption evaluation is biased. An original
      alcohol consumption evaluation is explained: ordinal factor analysis, and
      evaluation scales are described. This study shows several people groups, whose
      sensitivity about alcohol consumption safety varies greatly: from people whose
      alcohol consumption is low and have a bad picture of alcohol, to people whose
      consumption is high, have a good picture of alcohol, or think that their
      consumption is low or normal. In fact, for the last ones, alcohol consumption
      safety will never be effective.

PMID- 8154790
TI  - [Poisonous birds: the Pitohuis of New Guinea].

PMID- 8154791
TI  - [Words, memory and pharmacy].
AB  - Etymology is useful for acquiring and properly using vocabulary. Words are
      precise tools. Exactness in the meaning of the words used is needed when new
      scientific words are created.

PMID- 8154792
TI  - [Luminescence and detection in liquid chromatography. II--Energy transfer from a
      stimulated molecule: indirect potentialization or sensitized luminescence].
AB  - Under the words of sensitized luminescence, the processes who include the
      transfers of energy from a donor to an acceptor are described. They are to the
      origin of new possibilities of detection in liquid chromatography by emission or
      inhibition of phosphorescence and fluorescence. These news technologies are
      illustrated by examples in pharmaceutic, biologic or food applications.

PMID- 8154793
TI  - [Effect of nalbuphine on external pancreatic secretion in rats].
AB  - Pancreatic secretion is controlled by neural and endocrine mechanisms. The
      administration of 2-desoxyglucose (2DG) to rats stimulates pancreatic secretion
      through a mainly vagal pathway, and provides an useful pharmacological model to
      study the agents (especially opiates and adrenergic drugs) which can modulate
      this neural pathway. In the present study, basal and 2DG-stimulated pancreatic
      secretion were measured in anesthetized rats. Nalbuphine had no effect on basal
      secretion; it antagonized 2DG-induced pancreatic stimulation in a dose-related
      fashion between 0.5 and 15 mg/kg iv. The effect of nalbuphine was suppressed by
      naloxone, but not by alpha and beta-adrenoceptor blocking agents, indicating an
      essentially opiate effect. In order to test whether an inhibition of kappa
      receptors participates in the nalbuphine effect, centrally or peripherally acting
      kappa agonists were associated with nalbuphine. Neither U50488H, nor ICI204448
      changed 2DG stimulation and nalbuphine effect. In conclusion, the effect of
      nalbuphine on 2DG-stimulated pancreatic secretion was similar to that of
      methadone and buprenorphine, required larger doses, and seemed to mainly involve
      mu receptors.

PMID- 8154794
TI  - [Research of antiparasitic agents: 1(nitrophenyl)-3-(methyl-3-indolyl)-prop-2-ene
      1-ones (Nitroindolylchalcones)].
AB  - The synthesis and the study of the antiparasitic properties of various 1-(nitro
      phenyl)-3-(methyl-3-indolyl)-prop-2-ene-1-ones (Nitroindolylchalcones) show
      interesting antiprotozoal activities on E. histolytica and T. vaginalis. No
      significative activity appears in vivo with animals on helminthes.

PMID- 8154795
TI  - [Pharmaceutical inspection in the European context].
AB  - Pharmaceutic Inspection has more or less the same mission in all of the European
      countries. Nevertheless, the diversity of its organization and of the ways in
      which it works is greater than might be imagined. It seems necessary that all
      pharmacists, inspectors and inspected alike, should discover the richness and
      usefulness of it. Indeed, the development of the European Community should lead
      to a greater harmonization without at the same time meaning that new structures
      have to be created. With this aim in mind, pharmacist inspectors getting together
      and exchanging information will have a vital role.

PMID- 8154796
TI  - [Contamination of ternary mixtures of parenteral nutrition by barium].
AB  - Patients treated with chronic parenteral nutrition develop metabolic bone
      diseases. Because of the chemical relationship between barium and calcium, and
      the barium bone affinity, a possible responsibility of this element in this bone
      pathology has been searched. The study of the different parenteral nutrition
      components shows that significant concentrations of barium have been found in
      total parenteral nutrition bags.

PMID- 8154797
TI  - [Quantitative structure-hypoglycemic activity relationships of some thiazolidine
      and imidazolidine-2,4-diones].
AB  - Quantitative structure-activity relationships are described for twenty six title
      compounds. Five compounds exhibit a significant hypoglycemic activity like
      insulin used as standard. The aim of the present paper is to investigate the
      contribution of the different substituents in the biological activity. The
      application of Fujita-Ban and Hansch models has shown that lipophilic and
      electronic parameters seem to be the best explanation of variance of biological
      data.

PMID- 8154798
TI  - [Protein assay by the modified Dumas method applied to preparations of plasma
      proteins].
AB  - Quantify protein according Pharmacopoeia method, based on Kjeldahl method, needs
      a long time to do. The development of an automaton which used the modified Dumas
      method divide the analysis time by 15 (6 minutes versus over 90 minutes). The
      results show no statistical differences between official method and this one.

PMID- 8154799
TI  - [Chromatographic sorbents for the preparative separation of proteins].
AB  - Chromatography separation steps are technologically very well accepted in
      downstream bioprocessing, but progresses are expected on productivity level as
      well as on cleanability. At large production scale, the driving force for
      purification processes is the throughput intended as the amount of material
      separated at a given velocity and for a defined level of purity. The possibility
      to play on some phases of the separation cycle and on the variation of dynamic
      binding capacity are clearly useful to diminish the separation time while
      maintaining high levels of loads. On the other hand, to sanitize properly the
      sorbents, it has been found that only very strong solutions such as alkaline
      ethanol or alternated acidic-alkaline solutions are effective. In this general
      situation, special sorbents are now proposed, withstanding stringent operational
      situations.

PMID- 8154800
TI  - A day of day plastic surgery in a district general hospital.
AB  - In spite of the suitability of the day surgery environment for most patients
      undergoing elective plastic surgery, day plastic surgery has not been universally
      adopted in the United Kingdom. The experience of one plastic surgeon gained in
      treating 5970 patients as day cases out of a total of 12,461 patients over 10
      years is described, with emphasis on the organisation of the service by only the
      consultant surgeon in collaboration with a medical secretary. Thus, neither the
      trainee surgeon nor GP clinical assistant in the team have any administrative
      duties. Within a day surgery unit with a twin theatre and 12 beds, it was
      possible on 1 day each week between July 1991 and June 1992 to treat 954 patients
      of whom 678 were treated under local anaesthesia and 276 under general
      anaesthesia. Three patients required admission to the main hospital overnight. By
      this day of day plastic surgery an effective service is provided to patients
      convenient to their home while also releasing facilities in the main regional
      centre which is equipped and staffed to a higher level of reconstructive
      expertise. However, the patients themselves should also play a part in improving
      the service intended for them, and a failure to attend for surgery without prior
      warning adds an avoidable element of inefficiency.

PMID- 8154801
TI  - An alternative method of tourniquet padding.

PMID- 8154802
TI  - Description of the Japanese method of radical gastrectomy.
AB  - This is a detailed description of the technique of 'R2' radical gastrectomy for
      cancer, used in Japan. Points of anatomical and technical interest which are
      omitted in currently available published outlines of the operation are emphasised
      to provide a guide of practical value to Western surgeons who wish to adopt the
      technique.

PMID- 8154803
TI  - Triple suspension rectopexy for complete rectal prolapse.
AB  - Twenty-eight patients with complete rectal prolapse were treated by a three-level
      triple suspension abdominal rectopexy with no recurrence and with improvement of
      rectal function. Rectal suspension was effected by three steel wire slings.

PMID- 8154804
TI  - Long-term outcome of patients presenting with acute complications of diverticular
      disease.
AB  - The immediate management of acute diverticular disease is well defined but the
      risk of further complications and the long-term course of the disease, after
      conservative or surgical treatment, is not clearly documented. Over an 8-year
      period, a total of 164 patients (male/female = 69/95, median age 68 years)
      presented with acute complications of diverticular disease and were prospectively
      followed up for a median of 48 months. Medical treatment of acute diverticulitis
      was effective in 85% of 86 patients, with a mortality of 1.3% and a recurrence
      rate of 2% per patient year follow-up. All 37 patients presenting with bleeding
      responded to conservative management without mortality and a readmission rate,
      with further bleeding, of 5% per patient year. Patients who required colonic
      resection (n = 52), either as a single or staged procedure, had a mortality of
      12% but with no further admissions with complications of diverticular disease.
      The low risk of readmission with recurrent disease after successful conservative
      treatment of the acute complications of diverticular disease does not justify
      elective operation in this group of patients.

PMID- 8154805
TI  - Endoscopic transanal resection (ETAR) of colorectal strictures in stapled
      anastomoses.
AB  - Anastomotic strictures complicating colorectal anastomoses can be difficult to
      treat. Endoscopic transanal resection (ETAR) using cutting electrocautery has
      been described for benign and malignant polypoid rectal lesions, but is not a
      well-recognised method of treating anastomotic strictures. There are possible
      theoretical risks to limit the effectiveness of this method in stapled
      anastomoses. We report five patients with stapled colorectal anastomotic
      strictures all treated successfully without complication by ETAR, and recommend
      this treatment option.

PMID- 8154806
TI  - Videothoracoscopy in the diagnosis of intrathoracic pathology: early experience.
AB  - We report our experience using the new technique of videothoracoscopy in the
      diagnosis of intrathoracic pathology. In the last 12 months, 40 patients (24
      male; 16 female) have undergone investigation by this method. Lung biopsy has
      been performed in 17 patients, pleural biopsy in 20 patients and mediastinal
      biopsy in three patients. The majority had been referred after other
      investigations had been inconclusive. All biopsies were diagnostic except one
      mediastinal biopsy. This early experience suggests that videothoracoscopic biopsy
      is a well-tolerated technique with high diagnostic yield.

PMID- 8154807
TI  - Local complications after arterial bypass grafting.
AB  - We have documented prospectively the problems occurring after 496 arterial bypass
      grafts (149 aortoiliac, 238 femorodistal, 65 extra-anatomic, and 44 others)
      implanted during the period 1987 to 1991 in a district general hospital.
      Postoperative bleeding occurred early in 14 (2.8%), and later (because of
      infection) in 3 (0.6%). Early graft occlusion (< 30 days) was seen in 2.9%
      aortofemoral, 10.4% femoropopliteal, and 25.3% femorotibial grafts, and
      amputation was required after 6.9% grafts. Wound problems were most common after
      femorotibial bypass--weeping of fluid in 3% and dehiscence or infection in 13.9%.
      Lymphatic collections occurred after 1.2% operations involving groin incisions.
      Graft sepsis was usually late, affecting 6% aortofemoral, 2.9% femorodistal, and
      7.7% extra-anatomic grafts, but no intra-abdominal aortic grafts. These figures
      are probably representative of the complication rates seen by many surgeons and
      serve as an example for comparison and criticism.

PMID- 8154808
TI  - GORA: a scoring system for the quantification of risk of graft occlusion.
AB  - Auditing the outcome from vascular surgery with regard to graft occlusion is made
      difficult by variations in the type of surgery performed and the case mix. These
      difficulties are compounded when attempting to compare units. In the present
      study we have attempted to develop a scoring system to predict the risk of graft
      occlusion, and thus compensate for these variables. Prospectively collected data
      from 214 consecutive patients undergoing vascular reconstructive surgery (233
      arterial grafts) were analysed. Graft occlusion occurred in 82 patients (35.2%).
      Using a multivariate linear regression analysis of these data a five-factor, five
      grade scoring system has been devised (GORA: Graft Occlusive Risk Assessment).
      Logistic regression analysis of the observed risk of occlusion with this derived
      score produced the following relationship between the odds ratio of occlusive
      risk and GORA score: (logeR/1 - R = (0.229 x score) - 4.165). The score was then
      validated in a different group of 186 patients (196 arterial grafts). In both
      groups the score was found to predict accurately the risk of graft occlusion (P <
      0.001). There was no significant difference in the receiver operating
      characteristic curves between the estimation and validation groups.

PMID- 8154809
TI  - 'Tactile sensation': a new clinical sign during fine needle aspiration of breast
      lumps.
AB  - The tactile sensation (TS) felt during fine needle aspiration (FNA) of
      symptomatic breast abnormalities was recorded prospectively in 169 patients. TS
      was classified as malignant (if 'gritty'), or benign (if 'rubbery', 'soft' or
      'fibrous'). This assessment was compared with fine needle aspiration cytology
      (FNAC) and the final diagnosis, to evaluate the clinical utility of TS. A
      'gritty' TS was recorded in 55/59 cancers and 22/110 benign lesions (sensitivity
      93.2%, specificity 80%). Comparison of TS and FNAC in 69 patients with definitive
      histopathology revealed complementary results (TS, sensitivity 88.9%, specificity
      48.5%; FNAC, sensitivity 55.6%, specificity 100%). Combining the sensitivity of
      TS with that of FNAC increased the overall sensitivity to 97.2%. Recording TS
      during FNA of symptomatic breast lumps enhances diagnosis, and alerts the
      clinician to the possibility of an underlying carcinoma when FNAC fails to
      confirm malignancy.

PMID- 8154810
TI  - Local anaesthesia and inguinal hernia repair: a cautionary tale.
AB  - Two patients undergoing inguinal herniorrhaphy developed transient quadriceps
      paresis after local inguinal nerve block. One sustained a compound fracture of
      the distal tibia and fibula. The importance of warning the patient and of
      increasing the awareness of nursing staff to the possibility of quadriceps
      weakness after use of local anaesthetic is emphasised.

PMID- 8154811
TI  - Clinical guidelines on the management of groin hernia in adults.

PMID- 8154812
TI  - Role of pre-admission clinics in a general surgical unit: a 6-month audit.

PMID- 8154813
TI  - Surgery and Lister.

PMID- 8154814
TI  - Reduction in incidence of glove perforation during laparotomy wound closure by
      'no touch' technique.

PMID- 8154815
TI  - Post-cholecystectomy symptoms after laparoscopic cholecystectomy.

PMID- 8154816
TI  - Management of extensive facial basal cell carcinoma by excision and microvascular
      tissue transfer.

PMID- 8154817
TI  - Abdominal tuberculosis.
AB  - The abdomen is involved in 10% to 30% of patients with pulmonary tuberculosis.
      The diagnosis is not difficult in societies where the disease is common and
      clinicians are aware of it. While previously rare in Western countries, the
      incidence is now rising among immigrants, and patients with AIDS. In HIV-infected
      patients, the disease is of a rapidly progressive nature, often fatal through
      usually treatable, but the diagnosis is difficult and often delayed. Treatment is
      essentially medical but occasionally surgical operation is necessary.

PMID- 8154818
TI  - Management of tuberculosis of the spine with neurological complications.
AB  - Tuberculosis is still a major cause of spinal compression in the developing
      countries. In this study 200 patients presenting with neurological lesions
      secondary to tuberculosis of the spine have been classified according to the
      Frankel classification and the results evaluated. A combination of surgical
      decompression and chemotherapy is advocated. The dangers of non-operative
      treatment are discussed.

PMID- 8154819
TI  - Gunshot wounds of the spine: should retained bullets be removed to prevent
      infection?
AB  - We have investigated the role of retained bullets and other possible risk factors
      in the development of local septic complications after gunshot wounds (GSW) of
      the spine. Of 153 patients with GSW of the spine followed up for a mean of 28
      months, the overall incidence of bullet wound related septic complications was
      9.8%. In 81 patients the bullet was retained and the incidence of local septic
      complications was 7.4%. In 72 patients the bullet left the body (70) or was
      removed on admission (2), and the sepsis rate was 12.5% (P > 0.05). In 24
      patients there was an associated colonic injury and the incidence of sepsis was
      8.4% compared with 5% in the group of patients with intra-abdominal injuries but
      no colonic trauma (P > 0.05). The incidence of septic complications in lumbar
      spine injuries was significantly higher than in thoracic and cervical spine
      injuries (P > 0.05). We believe that in GSW of the spine, retained bullets do not
      increase the likelihood of septic complications.

PMID- 8154820
TI  - Who should check our tools?

PMID- 8154821
TI  - Nocturnal orthopaedic operating: can we let sleeping orthopaedic surgeons lie?
AB  - A 12-month retrospective study of emergency orthopaedic operations in a district
      general hospital was performed. There were 962 emergency admissions of whom 272
      (17.7%) underwent emergency operation. The largest group consisted of those
      undergoing operation for femoral neck fractures (37.6% of the total). Despite
      58.8% of the patients presenting to the accident and emergency (A&E) department
      between 0800 and 1700 hours, the majority (66.2%) were operated on 'out-of
      hours'. Those patients undergoing emergency operation out-of-hours were allocated
      to one of three categories (emergency, urgent, or scheduled) depending on the
      nature and severity of their presenting condition. In the authors' opinion, 81.9%
      of the patients could have been appropriately classified as scheduled cases and
      that all out-of-hours operating in this group of patients could have been
      deferred until the following morning. This would have reduced the number of
      orthopaedic operations performed out-of-hours from 182 to 33. The operating time
      at night would have been reduced from 126.9 h to 15.8 h. The implications of this
      study are important in view of the currently proposed changes in the hours worked
      by surgical trainees, the CEPOD findings, and the Government's proposals outlined
      in Achieving a Balance.

PMID- 8154822
TI  - Perioperative autologous blood transfusion in elective total hip prosthesis
      operations.
AB  - The aim of this study was to determine if acute perioperative normovolaemic
      haemodilution with retransfusion of the autologous blood at the end of operation
      would reduce or eliminate the need for homologous (banked) blood. Forty patients
      scheduled for total hip prosthesis replacement (THPR) were randomly divided into
      two groups: Group A, 20 patients from whom 900 ml of blood was taken 20 min
      preoperatively, the volume being replaced with 1000 ml of gelatin solution
      (Haemaccel). Group B, 20 patients who were undergoing the same operation but from
      whom no blood was taken. Both groups were allowed a fall in haematocrit (Hct) to
      0.25 before transfusion was started. A standard formula to calculate allowable
      blood loss plus intraoperative Hct measurements were used to achieve the
      haemodilution. There was no significant difference in blood loss between the two
      groups. Transfusion requirement was the same in the two groups. In this study,
      autotransfusion by the withdrawal of 900 ml of blood is inadequate to reduce the
      transfusion requirement further than that which can be achieved by haemodilution
      alone.

PMID- 8154823
TI  - Hand infections secondary to fish bone injuries.
AB  - Hand injuries associated with fish bones and fin spines are not common but can
      cause morbidity out of proportion to the original injury. This is because such
      injuries often leave residual fragments of foreign organic matter in the tissues,
      leading to troublesome secondary infections. This report details 1 year's
      experience with nine hand infections after fish bone injury in a busy regional
      hand surgery referral centre. There were five males and four females with an
      average age of 45 years. Radiographs taken on presentation in five patients
      revealed a radiolucent foreign body in only two patients. Two patients presented
      with a flexor tendon sheath infection, three with a pulp space infection, one
      with infection of the hypothenar space, one with a subungual infection, one with
      cellulitis of the dorsum of the hand and one with an abscess on the dorsum of the
      hand. Antibiotics were prescribed for six patients and all patients except the
      one with cellulitis of his hand underwent surgical debridement. A single surgical
      procedure was adequate in five patients. One patient with a hypothenar space
      infection only had the foreign body removed during the third surgical
      debridement. The two patients with flexor tendon sheath infections required ray
      amputation. Fish bones cause a number of different infections in the hand. A
      foreign body should always be sought even if not present on the radiograph.
      Antibiotic selection should be tailored to eradicate the causative organism.

PMID- 8154824
TI  - New bone and connective tissue ingrowth in a hydroxyapatite block repairing a
      rabbit skull defect.
AB  - Standardized 11 mm rabbit skull trephine defects were implanted with 9 mm
      diameter hydroxyapatite (HA) blocks. New bone and connective tissue ingrowth was
      studied histologically and by X-ray after 8, 12 and 16 weeks. Empty defects
      without HA served as controls. Increasing amounts of new bone and fibrous
      connective tissue appeared inside the pores of the HA block with time. The
      interface area was constituted at 8 weeks predominantly by fibrous connective
      tissue which changed gradually at 12 weeks and definitely showed a solid bony
      union between the HA block and the host bone at 16 weeks. Movement of the implant
      was a possible reason for the prolonged healing time. However, trabecular new
      bone ingrowth appeared slowly even though a contact between the host bone and the
      HA block was not primarily provided. Comparison between a calvarial defect
      inserted with an HA block and an empty defect is not critically valuable,
      although the amount of new bone increased and that of connective tissue decreased
      in the empty defect during 16 weeks of observation. At the end of the experiment
      the HA-filled defect was seen to be totally repaired while the empty control
      defect was repaired with new bone to about half of its area.

PMID- 8154825
TI  - A composite of natural coral, collagen, bone protein and basic fibroblast growth
      factor tested in a rat subcutaneous model.
AB  - A rat subcutaneous model was used to test the osteoinductive efficacy of a
      composite consisting of natural coral, collagen, a bone morphogenetic protein
      like material [termed bone protein (BP)], and basic fibroblast growth factor
      (bFGF). Results indicated good ossicle formation only when BP was present,
      whether with or without bFGF. Initially, cartilage and mineralized cartilage were
      apparent. With time, osteoblastic bone formation and hematopoietic marrow were
      evident. bFGF may have enhanced the maturation of the ossicles in the early
      stages. Coral-collagen appears to be a good carrier vehicle for BP and should be
      tested in a bony site. This would allow the osteoconductive property of coral to
      be expressed.

PMID- 8154826
TI  - Effects of basic fibroblast growth factor on bone allografts. A study using bone
      harvest chambers in rabbits.
AB  - Bone grafts which have been supplemented with a growth factor might incorporate
      faster. In this study we investigated the effect of basic fibroblast growth
      factor (bFGF). Titanium bone harvest chambers were implanted bilaterally in the
      proximal tibia of rabbits. These chambers were pierced by a transverse bone
      ingrowth canal from which 1 x 1 x 5 mm cancellous bone rods were repeatedly
      harvested at 5 weeks intervals. The bone rods to be used as allografts were
      frozen as ordinary bank bone, and then lipid-extracted. This treatment yields a
      graft which elicits less of an immunologic response than allografts which are
      only frozen and thawed. Before implantation, the bone rods were soaked in a
      cellulose gel containing 0.5 microgram/ml recombinant human bFGF or gel without
      bFGF as a control. The grafts were then implanted pair wise (bFGF and control) in
      the chambers of recipient rabbits. These chambers were harvested after 2 weeks.
      Evaluation was made by Tc-MDP scintimetry, histomorphometry and histology. Upon
      histology new living tissue had filled the grafted chambers entirely and partly
      replaced the graft. bFGF induced an increased amount of pre-osteoblastic tissue
      in the bFGF-treated grafts (p < 0.02), but there was no difference in the amount
      of osteoid or new bone.

PMID- 8154827
TI  - Delivery systems for bone morphogenetic proteins. A summary of experimental
      studies in primate models.
AB  - The characterization and molecular cloning of the family of the bone
      morphogenetic proteins (BMPs) have laid the foundation for the cellular and
      molecular analysis of bone development and regeneration. A carrier substratum is
      required, however, to optimize osteogenic activity initiated by BMPs bound to the
      surface of the carrier. Native and recombinant human (rh) BMPs induce local
      endochondral bone formation in conjunction with the insoluble collagenous bone
      matrix, the inactive residue obtained after dissociative extraction of the matrix
      with chaotropic agents. While the cellular and molecular biology of BMPs and
      related members is advancing at a furious pace, progress in the formulation and
      implementation of novel delivery systems has been slow. The creation of inorganic
      nonimmunogenic carriers with defined geometries capable of delivering BMPs in the
      absence of the collagenous matrix is a crucial goal for skeletal
      reconstructionists and molecular biologists alike. Significant advances in
      skeletal reconstruction may be expected when novel carrier substrata are
      implemented for delivery of optimal doses of now available recombinant human
      BMPs.

PMID- 8154828
TI  - Induction of new bone by allogeneic demineralized bone matrix combined to
      bioactive glass composite in the rat.
AB  - Allogeneic diaphyseal demineralized bone matrix (DBM) cylinders containing
      bioactive glass rods were implanted for 4 and 8 weeks in the abdominal muscle
      wall of rats. DBM without glass served as control. The results suggest that new
      bone induction by DBM was accelerated by the presence of bioactive glass
      implants. However, the bone formation induced by DBM on the glass surface was
      relatively small. The biocompatibility of the glass was verified by the absence
      of adverse cellular reactions in the interface region between glass and bone. The
      method used provides a simple and fast means of exploring the characteristics of
      potential bone substitutes.

PMID- 8154829
TI  - Morphology of osteogenesis in bioactive glass interface.
AB  - Bone formation around bioactive glass implants (S56.5P4) in the trabeculous
      subchondral bone in the distal femur of rabbits was studied by histology and
      scanning electron microscopy. Three types of tissue: bone, connective and
      hematopoietic tissue developed around the implants resulting in lamellar new bone
      covering 76% of the surface of the implants at twelve weeks. Bone formation
      around implants began as woven bone changing mainly to lamellar, osteon like new
      bone in contact with the S56.5P4 surface. Endochondral ossification was absent.
      In the area of bone containing hematopoietic tissue, new bone grew often as a
      thin layer along the implant surface. However, bone seemed to form adjacent to
      the implant surface through osteo-conduction. Only 21% of the implant surface was
      covered by loose connective tissue. Some proteoglycan containing thin fluid
      filled spaces were seen ten days after implantation. In few areas with apparent
      breakdown of the implant surface decreased amount or no bone formation was
      observed. Von Kossa method stained the reaction layer as two parallel dark brown
      lines, toluidine blue as two blue stripes, whereas van Gieson did not stain the
      reaction layer at all. In conclusion, the present histological results indicate
      bone bonding, which is a physico-chemical process observed between S56.5P4
      implant and host bone.

PMID- 8154830
TI  - Effect of bovine bone morphogenetic protein and bioactive glass on demineralized
      bone matrix grafts in the rat muscular pouch.
AB  - New bone formation induced by allogeneic demineralized bone matrix (DBM) and bone
      morphogenetic protein (BMP) combined with bioactive glass (BG) was studied in a
      rat abdominal muscle pouch model. At four weeks the amount of new bone was not
      influenced by DBM combined with BMP and/or bioactive glass. The mean proportional
      areas of new bone varied among different DBM test groups from 8.6% to 13.4%. New
      bone was induced in inactivated DBM samples containing BG, while no bone
      formation was seen in DBM samples without BG. The results indicate that bioactive
      glass favours bone induction in inactivated allogeneic bone matrix.

PMID- 8154831
TI  - Purification of monocomponent bovine bone morphogenetic protein in a water
      soluble form.
AB  - Noncollagenous protein material was extracted from HCl-demineralized bovine bone
      particles in 4 M guanidinium hydrochloride. Water- and citrate buffer-insoluble
      material was collected, solubilized in 6 M urea and fractionated by preparative
      isoelectric focusing using a running voltage of 5000 V. The material removed from
      the area between pH 4.7 and 5.7 of the isoelectric focusing gel was
      osteoinductive (identified by its capacity to induce bone development). This was
      solubilized in 6 M urea and dialyzed against 0.2 M Tris buffer. The Tris buffer
      soluble material was fractionated by HPLC gel filtration. The water- and citrate
      buffer-insoluble material contained mainly high-molecular-weight protein
      complexes which were osteoinductive, and < 5% of the material was osteoinductive
      monocomponent bone morphogenetic protein. The Tris buffer-soluble material
      contained only two polypeptides: an osteoinductive peptide of molecular weight
      18,500 and a non-osteoinductive peptide of molecular weight 8,000. The very high
      voltage used during the isoelectric focusing caused a slow break-down of the urea
      soluted protein complexes, which significantly increased the yield of
      monocomponent bone morphogenetic protein. By the present method it is possible to
      prepare Tris buffer solution containing up to 2 mg/ml of pure monocomponent bone
      morphogenetic protein.

PMID- 8154832
TI  - Functional carriers for bone morphogenetic proteins.
AB  - This review covers advances in current researches on delivery systems for bone
      morphogenetic protein. In summary, it notes that the diversity of carriers,
      inorganic, organic and synthetic composite, have possessed physiochemical and
      biological properties and efficacy of delivery of bone morphogenetic protein
      promoting bone induction in experimental animals. It also traces a new trend in
      research on carrier systems for bone morphogenetic protein. A desirable carrier
      of BMP will bridge basic research with clinical application of bone morphogenetic
      protein.

PMID- 8154833
TI  - Functional delivery systems for bone inducing proteins.

PMID- 8154834
TI  - High yield of osteoinductivity can be derived from demineralized bone matrix
      using collagenase digestion.
AB  - A bone morphogenetic protein purification method for minor quantities of bone
      material was developed based on collagenase splitting of bone connective tissue.
      Our aim was to remove and characterize the osteoinductive protein preparation in
      native form without using strongly dissociative agents. We started from 80 g of
      HCl-demineralized reindeer bone material which was treated with type I collagen
      splitting collagenase. The solution was dialyzed against 10 mM glycine-HCl
      buffer, pH 5.2. The formed precipitate was found to be osteoinductive. After
      fractionation of the material using HPLC gel filtration it was observed that the
      high-molecular-weight component of the precipitate was biologically active.
      Isoelectric focusing revealed that the component consisted of at least eight
      different protein molecules. Lower-molecular-weight components induced no bone
      formation. These preliminary findings suggest that in native form at least one
      part of BMP is in a complex form and other extracellular matrix components bound
      to the osteoinductive protein complex are significant for BMP action and may act
      synergistically or as carriers for the BMP.

PMID- 8154835
TI  - Heat tolerance of activity toward ectopic bone formation by rabbit bone matrix
      protein.
AB  - The 4 M guanidine hydrochloride (GuHCl)-soluble bone matrix proteins which
      contained bone morphogenetic protein (BMP) were found capable of inducing ectopic
      bone and cartilage formation in mammals. This osteogenic capacity was resistant
      to high temperatures and mild heating actually increased the amount of bone
      induced, with a maximum occurring at 70 degrees C. The osteogenic potential was
      preserved after heating at 170 degrees C for 10 min or 140 degrees C for 30 min.

PMID- 8154836
TI  - Whole body irradiation does not affect induction of new bone development.
AB  - The effect of whole body irradiation given either beforehand to the donor or
      after implantation to the recipient rats on the inductive capacity of decalcified
      bone grafts was studied. In examining the effect of advance whole body
      irradiation of the donor animal, the grafts were harvested five days after the
      irradiation, non-irradiated rats serving as control donors. Error! Reference
      source not found-irradiation with doses of 800, 950 or 1100 rad was used. The
      grafts, implanted either alone or in composite form in the muscle pouches of non
      irradiated rats of an inbred strain, were removed four weeks after implantation
      and examined by measuring 45Ca uptake, ash weight and area of radio-opacity in
      roentgenographs. There were no differences in bone-inductive capacity between the
      grafts obtained after total body irradiation and the control grafts. In the other
      part of the study, decalcified bone grafts were implanted in the abdominal muscle
      pouches of the recipient rats, which were exposed to Error! Reference source not
      found.-radiation of 800 rad on either the second, 10th or 21st day after
      implantation. Four weeks after implantation the grafts were removed and examined.
      No differences in new bone formation were found between the groups subjected to
      irradiation at different times or between these and the non-irradiated controls.
      It is concluded that donor whole body irradiation of 800-1100 rad in rat has no
      significant effect on the properties of new bone developed in allogeneic
      decalcified bone grafts, neither does recipient 800 rad irradiation administered
      after implantation affect the bone induction activity.

PMID- 8154837
TI  - Changes in bone inducing activity of bone morphogenetic protein with aging.
AB  - In the future, the clinical application of bone morphogenetic protein (BMP) will
      be mainly in patients of advanced age. In this study, we examined changes in BMP
      activity due to aging in recipient rats. The bioassays were carried out with
      bovine bone matrix-derived BMP obtained by the Bessho's BMP purification method.
      The purified BMP with the atelopeptide type I collagen was implanted into the
      calf muscles of 5-, 10-, 20- and 40-week-old Wistar rats. Three weeks later, soft
      X-ray and light-microscopic examination disclosed new bone formation in each aged
      recipient rat. Bioassay revealed decreasing ALP activity and Ca content as the
      recipient rats became older. However, bone induction was detected even in the 40
      week-old Wistar rats. These results suggested that the bone inducing activity of
      BMP decreases proportionately as the recipient ages. Nevertheless, BMP offers
      considerable possibilities for clinical application in patients of advanced age.

PMID- 8154838
TI  - Heterotopic osteoinduction in a rat membrane-isolated latissimus dorsi island
      flap. A pilot study.
AB  - Applying our knowledge of heterotopic osteoinduction by bone morphogenetic
      protein (BMP) and demineralized bone matrix (DBM), we sought to induce
      ossification of membrane-isolated latissimus dorsi flaps in the rat. Our aim was
      to produce an animal model for a versatile "custom-made" bone island flap which
      could be used as a substitute for bone. Ten latissimus dorsi island flaps in nine
      Wistar rats, 5-6 weeks of age, were prepared using microsurgical techniques in
      aseptic conditions. The flaps were isolated from other tissues with silicone,
      Gortex or OpSite membranes. We applied 3-9 mg partially purified bovine BMP or
      0.1 -0.25mg BMP bound covalently to type IV collagen with 15mg DBM inside the
      flaps. We have five animals with eight implants of BMP and DBM in latissimus
      muscle pouches as rat bioassay controls. The results were evaluated after a
      period of three weeks using soft X-ray radiography and histology with hematoxylin
      eosin-azure II and Alcian blue stains. Positive radiological results were
      observed in 10/10 flaps (100%), in controls in 7/8 (87.5%). Positive histological
      results comprised 8/10 (80%) and in controls 7/8 (87.5%). Two flaps (20%) showed
      partial necrosis. These did not lower the percentage of either positive
      histological or radiological findings, but exemplified some of the problems which
      are faced in this kind of tissue engineering.

PMID- 8154839
TI  - The role of fibrin sealant in osteoinduction.
AB  - Mesenchymal cell stimulation and angiotropic effects suggest a fibrin sealant
      mediated enhancement of osteogenesis. For its glueing capacity fibrin sealant is
      also regularly used in bone surgery. However, its influence on osteoregeneration
      is debatable. The effect of fibrin sealant on bone matrix gelatin dependent
      ectopic and orthotopic osteoinduction in rats was studied. Neither biochemical
      nor histologic parameters revealed a direct influence of fibrin sealant on any
      osteoinductive process.

PMID- 8154840
TI  - Bone induction and bone repair by composites of bone morphogenetic protein and
      biodegradable synthetic polymers.
AB  - We developed adequate delivery systems for bone morphogenetic protein (BMP) to
      express its bone-inducing activity by combining it with biodegradable synthetic
      polymers, these causing no unfavorable tissue reaction or anti-BMP effect. Their
      efficacy was tested for ectopic bone formation in mice and reconstruction of
      large segmental bone defects of the tibiae in rabbits. Composites of semipurified
      BMP and polylactic acid--polyethylene glycol block copolymer (PLA-PEG), and
      composites of BMP, PLA-PEG and lactic acid--glycolic acid copolymer (PLGA) were
      implanted under the fasciae of the dorsal muscles of mice. Three weeks after
      implantation, both the BMP/PLA-PEG and BMP/PLA-PEG/PLGA composites were
      completely absorbed and replaced by newly induced bone with hematopoietic marrow.
      Because the BMP/PLA-PEG composite is a viscous semiliquid and the BMP/PLA
      PEG/PLGA composite is a plastic and moldable, the former can be used as an
      injectable bone-inducing material and the latter as a plastic mold. The BMP/PLA
      PEG/PLGA composites were implanted in large segmental bone defects in the tibiae
      in rabbits. Twelve weeks after implantation, the bone defect was completely
      restored by a newly formed bone mass of the original thickness and structure.

PMID- 8154841
TI  - Bone inductive potential and dose-dependent response of bovine bone morphogenetic
      protein combined with type IV collagen carrier.
AB  - Using type IV collagen as carrier, the expression of bovine bone morphogenetic
      protein (bBMP) activity and the relation of ectopic bone formation to BMP dosage
      in the reconstitution were investigated in BALB mice. Visible heterotopic bone
      was induced by GuHCl-extracted bovine BMP at a minimal dose of 0.5 mg within 21
      days after the BMP was covalently bound to type IV collagen of weight 5.6 mg. The
      dose-dependent osteogenetic response of BMP was retained in the BMP/type IV
      collagen composite. As the BMP dose increased in the reconstitution, the
      integrated intensity and area of bone and cartilage formation, as quantified by a
      computerized scanner, were enhanced. Degradation of the collagenous carrier was
      improved by BMP, and neovascularization of the implant site initiated by type IV
      collagen was also observed. The covalent binding of BMP to type IV collagen
      postponed the time-sequence of ectopic bone development induced by BMP alone. The
      conclusion was that the exaggerated and extended effects of type IV collagen on
      BMP are mainly due to chemotaxis to progenitor cells, immunogenetically inert,
      vascular initiation and biodegradability in type IV collagen.

PMID- 8154842
TI  - Localization of bone morphogenetic protein-induced bone and cartilage formation
      on a new carrier: fibrous collagen membrane.
AB  - A fibrous collagen membrane (FCM) made of crosslinked reconstituted collagen
      fibers was applied as a carrier of BMP. The effectiveness of FCM as a BMP carrier
      was compared with conventionally used insoluble bone matrix (IBM). Partially
      purified BMP was obtained from a guanidine HCl extract of bovine bone after a
      three-step chromatographic procedure. The BMP fraction was combined with FCM or
      IBM and implanted subcutaneously in the back of rats. Bone and cartilage
      formation were determined by radiographic, histologic, and biochemical analyses
      after removal at 1, 2, 3 and 4 weeks. After 2 weeks, bone and cartilage formation
      were evident histologically in IBM-BMP and FCM-BMP. In IBM-BMP, cartilage was
      formed in the area of presumptive bone. On the other hand, in FCM-BMP, cartilage
      formation occurred in the space between the fibers of fiber-bundles, while on the
      surface of the fibers bone formation started independently. Biochemically, the
      most noteworthy difference between FCM-BMP and IBM-BMP was the marked increase in
      type II collagen content in FCM-BMP, which contrasted with its decrease in IBM
      BMP at 3 weeks. This study demonstrated that FCM definitely functioned as a BMP
      carrier that led to bone and cartilage formation at distinct sites. Therefore, we
      conclude that BMP could induce differentiation of immature cells preferentially
      into either osteogenic cells or chondrocytes depending upon the nature of the
      carrier which provides the environment for cell differentiation.

PMID- 8154843
TI  - Granular hydroxyapatite and allogeneic demineralized bone matrix in rabbit skull
      defect augmentation.
AB  - To study the effect of hydroxyapatite (HA) granules on new bone formation induced
      by allogeneic demineralized bone matrix (DBM) and to ascertain the specific dose
      response of bone regeneration in rabbit calvarial defects, implantation with
      different doses of DBM, HA granules and a mixture of DBM with HA, respectively,
      was undertaken. The results showed that the largest quantity of cartilage in the
      fourth week and woven and remodeled bone covering almost the whole area of the
      defect in the tenth and twelfth week, was visible in the 20-30 mg but not in the
      40 mg DBM groups. New bone formation in the defects implanted with DBM and HA was
      markedly less than in those implanted with DBM alone and a large amount of
      fibrous tissue was initiated by HA granules. A significant negative correlation
      between new bone formation and fibrous tissue ingrowth was noted. HA granules, as
      disturbing the bone regeneration induced by DBM, are thus not a desirable
      combination, and a dose-block phenomenon according to the amount of DBM must be
      anticipated in repairing skull defects.

PMID- 8154844
TI  - Osteogenic activity of bone morphogenetic protein and hydroxyapatite composite
      implants.
AB  - In an experimental study in rats hydroxyapatite (HA) ceramics of characteristics
      and inactive rat bone matrix were investigated comparatively for their
      suitability as carriers for osteoinductive factors. Bone morphogenetic protein
      was extracted from long bones of pigs under dissociative conditions and partially
      purified by gel filtration. The resulting pBMP was combined with the granular
      hydroxyapatite ceramics Osprovit, Algipore, Frialit and inactive rat bone matrix
      (IBM) by precipitation of aliquots of this pBMP fraction onto pellets of each
      carrier material. The osteogenic activity of these composite implants and of
      corresponding controls was bioassayed by implantation into muscle pouches of
      immunodeficient rats. All pBMP-HA ceramic implants elicited ectopic bone
      formation within 25 days after implantation, whereas control implants did not
      show any osteoinductive ability. Alkaline phosphatase (AP) activity of the
      explant tissues was determined for quantitation of bone formation. Due to the
      high incidence of bone formation found in each pBMP group all HA ceramics tested
      seem to be basically suitable as carriers for osteoinductive factors. Algipore, a
      highly porous phycogen HA ceramic, was found to be quantitatively superior to all
      other materials investigated due to its very large surface available for protein
      binding.

PMID- 8154845
TI  - Paediatric reference ranges for urinary catecholamines/metabolites and their
      relevance in neuroblastoma diagnosis.

PMID- 8154846
TI  - Reversible extreme hyperlipidaemia in a patient with excessive ice cream
      consumption.

PMID- 8154847
TI  - Clinical evaluation of sodium ion selective field effect transistors for whole
      blood assay.
AB  - Sodium ion selective field effect transistors (ISFETs) were evaluated for their
      performance in measurement of sodium ions in whole blood for 'near patient'
      analysis in operating theatres and intensive care units. Performance was
      evaluated in comparison with a standard clinical laboratory sodium/potassium ion
      analyser (Radiometer KNA1) and with sodium and potassium assays using flame
      photometry on the plasma from each whole blood specimen. The imprecisions
      (coefficients of variation) of three ISFETs for sodium ion assay were 1.08, 1.56
      and 1.10%, respectively. Robust bivariate linear regression (reweighted least
      squares preceded by least median of squares) of the ISFET versus KNA1 sodium ion
      activity yielded a regression coefficient of 1.08 and an intercept of -18.2 mM.
      The influence of potassium, protein and lipid on the measurement of sodium ions
      by both ISFETs and the KNA1 was assessed using robust multiple regression (also
      based on reweighted least squares preceded by least median of squares). In the
      regression versus flame photometry, protein was found to be more influential for
      the KNA1 (glass sodium ion selective electrode) than for the ISFET. Potassium had
      no influence on assays using the ISFET, but had a weak negative influence on
      assays using the KNA1. Two ISFETs lasted for more than 200 assays each
      demonstrating their robustness in the assay of whole blood.

PMID- 8154848
TI  - The analysis of metabolites in human sweat: analytical methods and potential
      application to investigation of pressure ischaemia of soft tissues.
AB  - A straightforward technique was developed for sweat collection applicable to
      tissues subjected to external load without introducing distortion of underlying
      tissues, and for analysis of six metabolites in the collected sweat. Chloride was
      measured colorimetrically and lactate, urea and urate by enzymatic methods on a
      centrifugal analyser. Sodium and potassium were measured by flame photometry. The
      methods showed good precision, recovery and linearity. To assess the technique
      sweat was collected: (i) from the sacrum, ischium, forearm and calf in healthy
      individuals at 32 degrees C for 1 h; (ii) from the sacrum of healthy subjects at
      ambient temperature for 9 h; (iii) at ambient temperature from the sacrum of a
      patient with a history of pressure sores. Sweat rates were greater at the sacrum
      and ischium than the calf or forearm. There were differences in the
      concentrations of lactate and urea between sites but these were smaller when
      expressed as amount secreted. Sweat rates were significantly lower in groups (ii)
      and (iii), but sweat could be collected reliably. This technique has potential
      clinical application to the investigation of susceptibility to pressure sores.

PMID- 8154849
TI  - Differences between the sugar moieties of liver- and bone-type alkaline
      phosphatases: a re-evaluation.
AB  - We re-evaluated the differences between the sugar moieties of liver and bone
      alkaline phosphatases (ALPs). Sialic acid was added to ALP sugar moieties by
      alpha 2,3- or 2,6-sialyltransferase treatment of the asialo-form ALP
      (neuraminidase-treated ALP). Asialo-bone ALP was converted to a liver-like ALP by
      the 2,6-sialyltransferase treatment. The resulting liver-like ALP was less
      susceptible to neuraminidase than non-treated bone ALP, but was still labile to
      heat exposure at 56 degrees C like non-treated bone ALP. However, after the O
      linked sugar moiety had been released by additional treatment with O-glycanase
      the liver-like ALP became more heat stable at 56 degrees C, like non-treated
      liver ALP. Non-treated liver ALP reacted specifically with anti-liver ALP
      monoclonal antibody, and non-treated bone ALP reacted with both anti-liver and
      anti-bone ALP antibodies. The asialo-bone ALP still reacted with anti-bone ALP
      antibody, whereas the asialo-form liver ALP showed little, if any, reaction with
      anti-liver and anti-bone ALP antibodies. Neuraminidase and O-glycanase-treated
      bone ALP reacted less with anti-bone ALP antibody. After O-glycanase treatment,
      bone ALP molecules deprived of an O-linked sugar moiety had a molecular size and
      heat stability similar to liver ALP. The difference between liver and bone ALP
      molecules may be due not only to their manner of sialic acid linkage but also to
      the attachment of the O-linked sugar moiety.

PMID- 8154850
TI  - Seasonal variation in serum 25-hydroxy vitamin D3 does not affect 1,25-dihydroxy
      vitamin D.
AB  - The seasonal variation of serum 25-hydroxy vitamin D3 and 1,25-dihydroxy-vitamin
      D has been investigated. Blood was taken from 27 healthy volunteers, aged 21-44
      years old at 3 monthly intervals over a period of 1 year. A scrolling monthly
      programme with 12 quarterly (3 month) time periods was developed. A summer
      associated increase in 25-hydroxy vitamin D3 was significantly correlated with
      but lagged behind by 2 months, the increase in recorded sunlight hours. However,
      four individuals showed no seasonal rise but maintained constant concentrations
      throughout the year within the established reference range. Serum 1,25-dihydroxy
      vitamin D showed marked intra-individual variability with no seasonal pattern
      although the highest concentration (180 pmol/L) was observed in the winter and no
      concentration greater than 108 pmol/L in the summer.

PMID- 8154851
TI  - Comparison of paired short Synacthen and insulin tolerance tests soon after
      pituitary surgery.
AB  - The cortisol responses to hypoglycaemia (insulin tolerance test, ITT) and
      tetracosactrin (short Synacthen test, SST) were compared after hypophysectomy to
      evaluate the SST for the assessment of hypothalamo-pituitary-adrenocortical (HPA)
      axis function in the immediate post-operative period. In 12 patients who were
      tested a mean of 21 months postoperatively (range 1-96) peak plasma cortisol in
      the SST correlated with that in the ITT (r = 0.90). Correlation was also seen in
      12 patients tested a mean of 9 days (range 4-18) after hypophysectomy (r = 0.73).
      Basal-peak cortisol increments did not correlate. The peak plasma cortisol
      response in each test was classified by comparison with a reference value of 550
      nmol/L. On this basis there was a notable discrepancy between the ITT and SST
      results in only one patient who was tested 4 days after hypophysectomy. The close
      correlation between ITT and SST responses after pituitary surgery extends into
      the immediate post operative period and indicates that the latter test can be
      used to screen HPA axis function at this time.

PMID- 8154852
TI  - Studies on red cell glucose-6-phosphate dehydrogenase: evaluation of reference
      values.
AB  - The analytical, intra-individual, inter-individual variation and reference values
      were determined for red cell glucose-6-phosphate dehydrogenase (G6PD). Different
      procedures for the conditions for storage of red blood cells and the preparation
      of haemolysates were investigated. A total of 2170 samples of blood were taken
      from apparently healthy persons-1212 males and 958 females--from randomly
      selected villages and city centres in the southern part of Turkey. Analytical
      variation, intra-individual variation and inter-individual variation were 8.67%,
      32.8% and 31.8%, respectively. The mean (SD) for G6PD was 8.6 (3.3) IU/gHb. The
      index of individuality, 1.03, showed that the reference intervals could be used
      for diagnostic purposes. Whole blood or a red cell pellet could be stored in
      physiological saline for one week at 4 degrees C or -20 degrees with little loss
      of activity. Two of three different procedures for the preparation of haemolysate
      gave data that showed no statistical difference and were equally satisfactory.

PMID- 8154853
TI  - The application of a new highly-sensitive radioimmunoassay for plasma 21
      deoxycortisol to the detection of steroid-21-hydroxylase deficiency.
AB  - 21-deoxycortisol (21-DF) is a steroid of strictly adrenal origin formed by the 11
      hydroxylation of 17-hydroxyprogesterone. This metabolic pathway is minor in
      normal subjects, in whom basal plasma concentrations range from 0.03 to 0.63
      nmol/L and from 0.865 to 1.50 nmol/L after adrenocorticotrophic hormone (ACTH;
      Synacthene Immediat, Ciba/Geigy, France). However, this metabolic pathway becomes
      major in 21-hydroxylase-deficient patients: in those who have the classical form
      of congenital adrenal hyperplasia (CAH) basal plasma 21-DF levels can attain more
      than 144 nmol/L. The synthesis of two isomers, E and Z, of the 21-deoxycortisol-3
      carboxymethyloxime (CMO) hapten enabled us to prepare the corresponding E and Z
      immunogens by coupling them to bovine serum albumin (BSA), as well as the
      corresponding iodinated E and Z 21-DF-3-CMO-histamine tracers. We developed a
      very sensitive radioimmunoassay for 21-DF in plasma by associating an anti-21-DF
      3-CMO-BSA-E isomer antibody to an iodinated 21-DF histamine-Z isomer (standard
      curve IC 50 = 8 pg/tube). This plasma 21-DF radioimmunoassay allowed diagnosis of
      the classical form of CAH in untreated newborn (basal 21-DF levels greater than
      144 nmol/L), as well as the late-onset form (post-ACTH 21-DF levels greater than
      11.54 nmol/L), and also permitted detection of 21-hydroxylase-deficient
      heterozygotes of both forms of CAH among the general population (post-ACTH 21-DF
      levels between 2.02 and 9.52 nmol/L).

PMID- 8154854
TI  - Lack of evidence for aromatase expression in human ovarian epithelial carcinoma.
AB  - It is controversial whether ovarian epithelial carcinoma possesses steroidogenic
      enzymes. We investigated aromatase expression in ovarian epithelial carcinoma,
      and compared it with the normal ovary and placenta. Samples were obtained from an
      ovarian carcinoma cell line SK-OV-3, ovarian tumour tissues from four patients
      with epithelial carcinoma and one patient with dysgerminoma. Aromatase enzymatic
      activity was measured in microsome fractions by quantitating 3H2O released from
      [1-3H] androstenedione and [3H]oestrone converted from [1,2,6,7-3H]
      androstenedione. Aromatase messenger ribonucleic acid (mRNA) was determined by
      reverse transcription-polymerase chain reaction (RT-PCR) using oligonucleotide
      primers synthesized according to the published human aromatase gene sequence. No
      aromatase activity was detected in either of two mucinous cystadenocarcinoma
      specimens or in SK-OV-3 cells, while aromatization proceeded with apparent
      Michaelis-Menten kinetics in the normal ovaries and placentas. The apparent Km
      value was 200 nmol/L for the ovary. Aromatase mRNA was detected in dysgerminoma,
      and the normal ovary and placenta, but not in any of three mucinous
      cystadenocarcinoma specimens, one serous cystadenocarcinoma specimen and SK-OV-3
      cells. These results for both enzyme activity and gene expression suggest that
      the human ovarian epithelial carcinoma lacks aromatase. The demonstration of
      absence of aromatase gene expression raises the possibility that aromatase
      activity in ovaries bearing epithelial carcinoma may be associated with
      hyperplastic stromal rather than tumour cells.

PMID- 8154855
TI  - Population screening for medium-chain acyl-CoA dehydrogenase deficiency: analysis
      of medium-chain fatty acids and acylglycines in blood spots.
AB  - We have developed methods for the measurement of the medium-chain fatty acids
      octanoate, decanoate and cis-4-decenoate and the acylglycines n-hexanoylglycine
      (HG) and 3-phenylpropionylglycine (PPG) in blood spots using gas chromatography
      and mass spectrometry. Normal ranges were obtained for octanoate and decanoate.
      HG, PPG and cis-4-decenoic acid were not detected in control blood spots. In
      blood spots from nine patients (including two newborn) with medium-chain acyl-CoA
      dehydrogenase (MCAD) deficiency, all metabolites were present in elevated
      concentrations although PPG was close to the detection limits and there was
      overlap for octanoate and decanoate. The lack of detection of cis-4-decenoic acid
      and HG in controls suggests that these are the metabolites of choice for blood
      spot identification of infants with MCAD deficiency.

PMID- 8154856
TI  - Secondary hyperlipidaemia: beyond the primary debate.

PMID- 8154857
TI  - Reference ranges for urinary N-acetyl-beta-D-glucosaminidase in healthy children
      determined with three colorimetric methods.

PMID- 8154858
TI  - Low serum levels of placental and placental-like alkaline phosphatase isoenzymes
      in women with blood groups A and AB.

PMID- 8154859
TI  - Association between serum cholesterol and leucocyte lysosomal function.

PMID- 8154860
TI  - Investigation of the potential for interference with whole blood glucose strips.

PMID- 8154861
TI  - Maternal serum-free beta-human chorionic gonadotrophin level: the effect of
      sample transportation.

PMID- 8154862
TI  - Isolated aldosterone deficiency progressing to Addison's disease in a 4-year-old
      girl.

PMID- 8154863
TI  - Dopa-responsive dystonia.

PMID- 8154864
TI  - Human vestibular cortex.

PMID- 8154865
TI  - Human prion diseases.
AB  - The prion diseases, sometimes referred to as the "transmissible spongiform
      encephalopathies," include kuru, Creutzfeldt-Jakob disease, and Gerstmann
      Straussler-Scheinker disease of humans as well as scrapie and bovine spongiform
      encephalopathy of animals. For many years, the prion diseases were thought to be
      caused by viruses despite intriguing evidence to the contrary. The unique
      characteristic common to all of these disorders, whether sporadic, dominantly
      inherited, or acquired by infection, is that they involve the aberrant metabolism
      of the prion protein (PrP). In many cases, the cellular prion protein is
      converted into the scrapie isoform by a posttranslational process that involves a
      conformational change. Often, the human prion diseases are transmissible to
      experimental animals and all of the inherited prion diseases segregate with PrP
      gene mutations.

PMID- 8154866
TI  - Vestibular cortex lesions affect the perception of verticality.
AB  - Seventy-one patients with unilateral supratentorial infarctions were evaluated
      with respect to static vestibular function in the roll plane, including
      determinations of the subjective visual vertical, skew deviation, and ocular
      torsion. Since animal studies have revealed at least four different areas of the
      parietal and temporal cortex involved in vestibular function, we tried to
      identify cortical areas in humans responsible for vestibular function in the roll
      plane. Infarcted areas, as demonstrated in magnetic resonance and computed
      tomography scans, were projected onto the appropriate sections of an atlas of the
      human brain. Infarctions in the territories of the posterior and anterior
      cerebral arteries did not affect static vestibular function in roll. Twenty-three
      of 52 patients with infarctions in the middle cerebral artery territory showed
      significant (p < 0.0005), mostly contraversive, pathological subjective visual
      vertical tilts. The overlapping area of these infarctions centered on the
      posterior insula, probably homologous to the parieto-insular vestibular cortex in
      the monkey. Although electrophysiological and cytoarchitectonic data in animals
      demonstrate several multisensory areas rather than a single primary vestibular
      cortex, the parieto-insular vestibular cortex seems to represent the integration
      center of the multisensory vestibular cortex areas within the parietal lobe.

PMID- 8154867
TI  - Single muscle fiber analysis of mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes (MELAS).
AB  - We examined muscle sections from 3 patients with mitochondrial myopathy,
      encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), using single
      fiber polymerase chain reaction, histochemistry, and in situ hybridization. Most
      type 1 ragged-red fibers showed positive cytochrome c oxidase activity at the
      subsarcolemmal region, while type 2 ragged-red fibers had little cytochrome c
      oxidase activity. However, there was no difference in the amount of total (mutant
      and wild-type) mitochondrial DNAs (mtDNAs) and the proportion of mutant mtDNA
      between type 1 and type 2 ragged-red fibers. These observations suggest that
      mitochondrial proliferation and nuclear factors affect muscle pathology,
      including cytochrome c oxidase activity, in MELAS. Total mtDNAs were greatly
      increased in ragged-red fibers (about 5-17 times over those in non-ragged-red
      fibers). The proportion of mutant mtDNA was significantly higher in ragged-red
      fibers (88.1 +/- 5.5%) than in non-ragged-red fibers (63.2 +/- 21.6%). Thus, the
      amount of wild-type mtDNA as well as mutant mtDNA was increased in ragged-red
      fibers in MELAS, failing to support the contention of a replicative advantage of
      mutant mtDNA. The proportion of mutant mtDNA was significantly higher in the
      strongly succinate dehydrogenase-reactive blood vessels (83.2 +/- 4.2%) than in
      non-succinate dehydrogenase-reactive blood vessels (38.8 +/- 16.2%). It seems
      likely that systemic vascular abnormalities involving cerebral vessels lead to
      the evolution of stroke-like episodes in MELAS.

PMID- 8154868
TI  - Eye movements in parkinsonian syndromes.
AB  - Eye movements were recorded in 14 patients with Parkinson's disease (PD) in the
      "off" condition, 14 patients with striatonigral degeneration (SND), 10 patients
      with corticobasal degeneration (CBD), and 10 patients with progressive
      supranuclear palsy (PSP), with comparison with 12 control subjects. Vertical
      saccade paralysis was not observed in the PD, SND, and CBD groups but was present
      in 9 patients of 10 in the PSP group. In the PD and SND groups, horizontal
      reflexive visually guided saccade latency and accuracy were similar, and differed
      only slightly from those of controls. In the CBD group, saccade latency was
      significantly increased and correlated to an "apraxia score"; whereas, in the PSP
      group, saccade amplitude was significantly decreased. Thus, the abnormalities of
      both horizontal saccade parameters in the PSP group contrasted with those
      observed in the CBD group. The percentage of errors in the antisaccade task, an
      index of prefrontal dysfunction, was markedly increased only in the PSP group.
      The smooth pursuit gain was decreased in all groups but more severely in the PSP
      group. It may be concluded that saccade abnormalities are clearly different in
      SND, CBD, and PSP, and might help in early differential diagnosis in individual
      patients, but that SND cannot be differentiated from PD on the simple basis of
      eye movement abnormalities.

PMID- 8154869
TI  - Posterior temporal epilepsy: electroclinical features.
AB  - In the course of evaluating children with posterior temporal lobe epilepsy with
      subdural electrodes, we observed that their seizures commonly arose from basal
      rather than convexity foci and that they followed a stereotyped clinical
      sequence. Seizures characteristically began with behavioral arrest that coincided
      with basal temporal seizure discharges and progressed to motor signs as the
      seizure activity spread to the ipsilateral cortical convexity. Behavioral
      automatisms were observed in approximately half the patients, but were never the
      first or most prominent ictal manifestation. Focal lesions were identified
      preoperatively in 7 patients. We performed tailored temporal lobe resections in
      14 patients, 10 (71%) of whom were seizure free (N = 9) or had occasional auras
      (N = 1) at a mean follow-up of 2 years. These findings suggest that in childhood,
      posterior temporal seizures frequently arise from basal cortex and have a
      consistent and recognizable ictal and electrographic semiology. In medically
      refractory patients, tailored temporal resection is an effective therapy.

PMID- 8154870
TI  - Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with
      late-onset Alzheimer's disease.
AB  - Amyloid plaques in Alzheimer's disease contain beta-amyloid, encoded by portions
      of exons 16 and 17 of the amyloid precursor protein. The specific association of
      rare amyloid precursor protein mutations with some kindreds with early-onset
      familial Alzheimer's disease suggests that specific abnormalities in amyloid
      precursor protein may contribute to the pathogenesis of Alzheimer's disease.
      Until now, there has been no evidence suggesting that amyloid precursor protein
      mutations could be involved in late-onset or sporadic Alzheimer's disease. We
      used reverse transcription-polymerase chain reaction, denaturing gradient gel
      electrophoresis, and direct DNA sequencing to analyze amyloid precursor protein
      exons 16 and 17 from postmortem cerebellar samples from patients with
      histologically confirmed Alzheimer's disease and control subjects. We found a
      novel point mutation, substitution of cytosine for guanine, at nucleotide 2119
      (amyloid precursor protein 770 messenger RNA transcript) in a patient with late
      onset Alzheimer's disease. This substitution deletes a BglII site and substitutes
      aspartate for glutamine at codon 665. Denaturing gradient gel electrophoresis
      analysis showed that this mutation was absent in 40 control subjects and 127
      dementia patients. Whether this mutation is a rare but normal variant or
      contributes to the development of Alzheimer's disease is not known. The BglII
      restriction fragment length polymorphism enables investigators to determine the
      frequency of this polymorphism in normal subjects and Alzheimer's disease
      patients.

PMID- 8154871
TI  - Autosomal-dominant cerebellar ataxia with retinal degeneration (ADCA type II) is
      genetically different from ADCA type I.
AB  - Autosomal-dominant cerebellar ataxia (ADCA) type II is a neurodegenerative
      disorder presenting with cerebellar ataxia and retinal degeneration. We analyzed
      the clinical features of 21 patients with ADCA type II from 3 Moroccan and 2
      French families. Mean age at onset was 17 years earlier in offspring than in
      their parents, compatible with anticipation. There was a suggestion of
      imprinting, with predominantly paternal transmission of early onset and severe
      forms of the affection. Candidate genes were tested in the family with the
      largest pedigree. The two known loci for ADCA type I (spinal cerebellar ataxia 1
      and 2) were excluded, as were candidate loci, retinitis pigmentosa 1 locus (RP1)
      and the genes for rhodopsin and peripherin-rds, responsible for autosomal
      dominant retinitis pigmentosa. ADCA type II does not therefore result from an
      allelic mutation of the tested genes for ADCA type I or autosomal dominant
      retinitis pigmentosa.

PMID- 8154872
TI  - Pretreatment with intraventricular basic fibroblast growth factor decreases
      infarct size following focal cerebral ischemia in rats.
AB  - Basic fibroblast growth factor is a polypeptide with potent multipotential
      trophic effects on central nervous system cells, including neurons, glia, and
      endothelial cells. In particular, it promotes the survival of a wide variety of
      brain neurons in vitro, and protects these neurons against the effects of several
      neurotoxins, including excitatory amino acids, hypoglycemia, and calcium
      ionophore. Since lack of substrate delivery, excitatory amino acid toxicity, and
      calcium entry into cells appear to be important processes in neuronal death after
      ischemia, we tested the hypothesis that pretreatment with basic fibroblast growth
      factor limits infarct size in a model of focal cerebral ischemia in vivo. Mature
      male Long-Evans rats received either continuous intraventricular infusion of
      basic fibroblast growth factor (1.2 micrograms/day; with or without heparin,
      added to stabilize the growth factor) or vehicle alone for 3 days before focal
      ischemic infarcts were made in the right lateral cerebral cortex by permanent
      distal middle cerebral artery occlusion and temporary (45-minute) bilateral
      carotid occlusion. Intraoperative measurements of core temperature, arterial
      blood pressure and blood gases, blood glucose concentration, and hematocrit, and
      postoperative measurements of temperature revealed no differences among vehicle-
      versus basic fibroblast growth factor-treated animals. Twenty-four hours later,
      animals were killed, brains were removed and stained to visualize cortical
      infarcts, and infarct volume was determined by image analysis. Overall, we found
      a 25% reduction in infarct volume in basic fibroblast growth factor- (N = 25)
      versus vehicle-treated (N = 23) animals (p < 0.01). This reduction was not
      enhanced by the addition of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8154873
TI  - Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient focal
      cerebral ischemia in rat.
AB  - We investigated the effect of an anti-CD11b monoclonal antibody (1B6c) on
      ischemic cell damage after transient middle cerebral artery occlusion. We divided
      animals into three groups: MAb 1 group (n = 5)--rats were subjected to 2 hours of
      transient occlusion and 1B6c (1 mg/kg) was administered intravenously at 0 and 22
      hours of reperfusion; MAb 2 group (n = 5)--same experimental protocol as MAb 1
      group, except that the initial dose of 1B6c was increased to 2 mg/kg; and control
      group (n = 5)--same experimental protocol as MAb 2 group, except that an isotype
      matched control antibody was administered. Animals were weighed and tested for
      neurological function before and after occlusion of the middle cerebral artery.
      Forty-six hours after reperfusion, brain sections were stained with hematoxylin
      and eosin for histology evaluation. We observed a significant reduction of weight
      loss and improvement in neurological function after ischemia in the MAb 2 animals
      compared to MAb 1 and vehicle-treated animals (p < 0.05). The lesion volume was
      significantly smaller in the MAb 2 group (19.5 +/- 1.9%) compared to MAb 1 (29.9
      +/- 2.6%) and vehicle-treated (34.2 +/- 5.4%) groups (p < 0.01). Tissue
      polymorphonuclear cell numbers were reduced in both 1B6c-administered groups. Our
      data demonstrate that administration of anti-CD11b antibody results in a dose
      dependent, significant functional improvement and reduction of ischemic cell
      damage after transient focal cerebral ischemia in the rat.

PMID- 8154874
TI  - Rett syndrome: controlled study of an oral opiate antagonist, naltrexone.
AB  - HYPOTHESIS: The opiate antagonist, naltrexone, will be beneficial in Rett
      syndrome. SUBJECTS: Twenty-five individuals fulfilling the criteria for Rett
      syndrome. METHOD: Randomized, double-blind, placebo-controlled crossover trial
      with two treatment periods, 4 months each, and an intervening 1-month washout
      period. Clinical stage, motor and cognitive development, motor-behavioral
      analysis, neurophysiological parameters (computerized electroencephalographic
      analysis, breathing characteristics, quantification of stereotyped hand
      movements, and sleep characteristics), and cerebrospinal fluid beta-endorphin
      measurements were evaluated at baseline and at the end of each treatment period.
      RESULTS: Only data from the first period of this study were analyzed due to
      significant sequence effects in the crossover design. This analysis indicated
      positive effects on certain respiratory characteristics including decreased
      disorganized breathing during wakefulness. Four (40%) of the individuals
      receiving naltrexone progressed one or more clinical stages versus none of the
      individuals receiving placebo. The adjusted (for baseline value and Rett stage)
      end of treatment psychomotor test age (Bayley Scales) was significantly higher
      for the placebo group. There was no significant change for the other parameters.
      CONCLUSION: Naltrexone may modify some of the respiratory disturbance in Rett
      syndrome. Declines in motor function and more rapid progression of the disorder
      suggest a deleterious effect.

PMID- 8154875
TI  - Cloning of human anti-GM1 antibodies from motor neuropathy patients.
AB  - Patients with multifocal motor neuropathy frequently have elevated titers of
      serum antibodies reactive with GM1 ganglioside. Although these antibodies may
      cause the syndrome, this has yet to be proven directly. As part of our studies on
      the nature and pathogenic potential of anti-GM1 antibodies, we have cloned B
      cells from the peripheral blood of 3 patients with multifocal motor neuropathy
      and generated four stable heterohybridoma cell lines secreting human monoclonal
      IgM anti-GM1 antibodies. In this report we describe the basic properties of these
      monoclonal antibodies in comparison with the patient's sera from which they were
      derived. The antibodies all differ in their pattern of reactivity with GM1 and
      other Gal(beta 1-3)GalNAc-containing glycoconjugates. They have widely varying
      thermal ranges and their reactivities are strongly influenced by the presence of
      accessory lipids. Affinity purification of the patient's sera with GM1 led to the
      identification of previously unrecognized paraproteins that were resolvable above
      the background of polyclonal anti-GM1 IgM. Our data demonstrate considerable
      heterogeneity in the immune response to GM1 both within individual sera and
      between different patients, which is likely to be of importance to their role in
      disease pathogenesis.

PMID- 8154876
TI  - Benign infantile familial convulsions are not an allelic form of the benign
      familial neonatal convulsions gene.
AB  - Benign infantile familial convulsions (BIFC) and benign familial neonatal
      convulsions (BFNC) are two forms of familial convulsions having an age of onset
      within the first year of life. The gene responsible for BFNC has been mapped to
      chromosome 20q in the close vicinity of D20S19 and D20S20 markers. We performed
      linkage analysis between BIFC and D20S19-D20S20 in eight families in order to
      know whether the BFNC gene is also implicated in BIFC. Several apparent obligate
      crossovers between affected members were detected. The data here presented
      demonstrate that the BFNC gene is not responsible for BIFC.

PMID- 8154878
TI  - Sequences of memory-guided saccades in Parkinson's disease.
AB  - Sequences of ocular saccades were studied in 8 patients with Parkinson's disease,
      with (i.e., "on") and without (i.e., "off") levodopa treatment. The amplitude of
      single saccades was decreased and not improved by treatment. The chronology of
      saccades during sequences was impaired in patients in the "off" state, but
      significantly improved during the "on" period. These results are compatible with
      a decreased activation of the supplementary motor area, which can be reversed by
      levodopa.

PMID- 8154877
TI  - Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine
      deficiency and lipid storage.
AB  - The use of zidovudine (AZT) for the treatment of acquired immunodeficiency
      syndrome (AIDS) induces a DNA-depleting mitochondrial myopathy, which is
      histologically characterized by the presence of muscle fibers with "ragged-red"
      like features, red-rimmed or empty cracks, granular degeneration, and rods (AZT
      fibers). Because dysfunctioning muscle mitochondria may lead to defects of beta
      oxidation of fatty acids, we examined the degree of neutral fat accumulation and
      muscle carnitine levels in the muscle biopsy specimens from 21 patients with AZT
      induced myopathic symptoms of varying severity. Six patients with no AZT fibers
      had normal endomyofibrillar lipid deposits and muscle carnitine levels; 7
      patients with fewer than 5 AZT fibers per field had a mild (+) to moderate (++)
      increase in lipid droplets, and reduced muscle carnitine levels (3 patients); and
      8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked
      ( ) increase in lipid droplets, and reduced muscle carnitine levels (6 patients).
      Serial sections showed lipid globules often within "cracks" or vacuoles of the
      abnormal muscle fibers. We conclude that the muscle mitochondrial impairment
      caused by AZT results in (1) accumulation of lipid within the muscle fibers owing
      to poor utilization of long-chain fatty acids, (2) reduction of muscle carnitine
      levels probably due to decreased carnitine uptake by the muscle, and (3)
      depletion of energy stores within the muscle fibers. The findings may have
      potential therapeutic implications in the treatment of AZT-induced myopathic
      symptoms using oral carnitine supplementation.

PMID- 8154879
TI  - Magnetic resonance spectroscopy of N-acetylaspartate in hypoxic-ischemic
      encephalopathy.
AB  - Magnetic resonance imaging and water-suppressed proton magnetic resonance
      spectroscopic imaging were used to study N-acetylaspartate and other metabolites
      in a patient with severe hypoxic-ischemic encephalopathy. The N-acetylaspartate
      signal, a putative marker of neuronal density, was markedly reduced in the
      forebrain. The relative signal intensity of choline-containing metabolites, which
      are more abundant in astrocytes than neurons, was increased. These results
      support the hypothesis that water-suppressed proton magnetic resonance
      spectroscopic imaging measurements of N-acetylaspartate may be useful for
      noninvasive detection of selective neuronal loss in a variety of disease states
      in the human brain.

PMID- 8154880
TI  - Dopamine transporter messenger RNA in Parkinson's disease and control substantia
      nigra neurons.
AB  - Dopamine transporter messenger RNA (mRNA) expression was assessed by in situ
      hybridization over individual pigmented neurons from the substantia nigra pars
      compacta in midbrain sections from 7 parkinsonian and 7 age-matched,
      neurologically normal patients. In the normal control brains, high levels of
      expression of dopamine transporter mRNA were noted over pigmented neurons in the
      substantia nigra pars compacta; neurons in the adjacent nucleus paranigralis of
      the ventral tegmental area displayed less hybridization. Nigra compacta neurons
      surviving in brains of patients with Parkinson's disease displayed only 57% of
      the dopamine transporter mRNA hybridization intensity displayed by nigral neurons
      in normal control brains. The disease-related decrease in the apparent level of
      dopamine transporter mRNA expression in remaining neurons could reflect neuronal
      dysfunction. Conceivably, it might also reflect differential vulnerability of
      those neurons that initially expressed higher levels of this transporter to the
      insult of parkinsonism.

PMID- 8154881
TI  - Early weight loss and high serum tumor necrosis factor-alpha levels in
      polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes syndrome.
AB  - We studied tumor necrosis factor-alpha (TNF-alpha) levels in serial serum samples
      from 3 consecutive patients who had a complete form of POEMS (polyneuropathy,
      organomegaly, endocrinopathy, M protein, skin changes) syndrome and early weight
      loss. Serum TNF-alpha levels were compared with those of 10 patients with
      multiple myeloma (5) or Waldenstrom's macroglobulinemia (5). Elevated serum
      levels of TNF-alpha were found in the patients with POEMS syndrome (two- to
      eightfold increase in 10 of 11 samples) and not in those with other malignant
      plasma cell dyscrasias. These results are in keeping with the hypothesis of a
      role for nonimmunoglobulinic mediators in the pathogenesis of the POEMS syndrome,
      and are consistent with previous reports of TNF-alpha overproduction in
      inflammatory demyelinating neuropathies and cachectic states.

PMID- 8154882
TI  - Apolipoprotein E4: phenotype in patients with Alzheimer's disease.

PMID- 8154883
TI  - [Molecular biology of cell death].
AB  - Apoptosis is an active mechanism for cell death that is characterized by unique
      biochemical processes, including nuclear condensation, cytoplasmic compaction and
      breaking up of the cells into a number of membrane-bound fragments called
      apoptotic bodies. Many physiological cell death is known to proceed by apoptosis,
      and importance of cell death in a variety of biological phenomena is now well
      recognized. Eukaryotic molecular biology resulted in the identification of
      several genes with an ability to modulate apoptosis. Some genes induce and the
      others inhibit apoptotic cell death. These include oncogenes (bcl-2, myc etc),
      anti-oncogenes (p53) and cell surface antigen genes (Fas, TNF receptor etc).
      Genetical approach to dissect programmed cell death, majority of which proceed by
      apoptosis resulted in the identification of several crucial genes involved in
      cell death processes (ced 3, ced 4, ced 9 etc. in C. elegans). In this chapter, I
      will overview genes involved in cell death, and show where we are now standing
      toward complete understanding of apoptosis in biochemical terms.

PMID- 8154884
TI  - [Cytotoxic action of alkylating agents in human tumor cells and its relationship
      to apoptosis].
AB  - Various anticancer agents have been known to induce apoptosis in certain types of
      human tumor cells. The fact that a variety of agents, which attack different
      cellular targets, induce common apoptotic cell death suggests that the nature of
      initial damage is not directly involved in apoptosis. The mechanism by which a
      damage leads to apoptosis is not known. However, modulation of this process may
      affect the outcome of anticancer drug treatment. This article briefly reviewed
      the studies of endogenous as well as exogenous factors which modulate apoptosis,
      and then described the characteristics of cell death induced by alkylating
      agents. O6-Alkylguanine, a major cytotoxic DNA damage produced by simple
      alkylating agents, can be repaired by the cellular enzyme O6-methylguanine-DNA
      methyltransferase (MGMT). About one-fifth of human tumor cell strains lack the
      MGMT activity and termed as Mer- cells. Mer- cells are hypersensitive to
      alkylating agents like chloroethyl nitrosoureas (CNUs), compared with repair
      proficient Mer+ cells. It is suggested that identification of a factor which
      suppresses the MGMT gene expression in CNU-resistant Mer+ cells, may enable us to
      convert these Mer+ cells to Mer- phenotype, thus resulting in much higher
      sensitivity of Mer+ cells to CNUs.

PMID- 8154885
TI  - [Radiation and apoptosis].
AB  - Apoptosis is a kind of programmed cell death, that is, intrinsically programmed
      "cell suicide process". Mammalian thymic lymphocytes, thymocytes, show a typical
      apoptosis immediately after a low dose irradiation. Apoptosis appears also during
      radiotherapy of tumor, especially of thymoma. Tumor suppressor gene such as p53
      and oncogene such as bcl-2 are found to be closely related to apoptotic processes
      in a cell. Possible mechanisms underlying interrelationship between expression of
      these genes, apoptosis and carcinogenesis were discussed.

PMID- 8154886
TI  - [Neuronal cell death and apoptosis].
AB  - Neuronal cell death is thought to be an important phenomenon not only for the
      developmental but also for the post-matured stages of the PNS and CNS neurons. In
      the developmental stages, massive neuronal death is observed at specific periods,
      e.g. the immediately after the arrival of axons to the postsynaptic target
      fields. This phenomenon is precisely programmed in the developing nervous system,
      so that they are called physiological or naturally occurring neuronal death. It
      has been shown that this programmed neuronal death is mediated by apoptotic death
      cascade, as follows: 1) neurotrophic agents, such as nerve growth factor, or
      afferent electrical input prevent neuronal death; 2) the macromolecular synthesis
      inhibitors, such as cycloheximide or actinomycin-D, prevent cell death; 3) DNA
      fragmentation is detected during the course of cell death; 4) variations of
      apoptotic morphology are observed in programmed neuronal death. Furthermore,
      recent studies also suggest that such apoptotic neuronal death occurs in the
      matured nervous system, e.g. neuro-degenerative diseases, such as Alzheimer's and
      Parkinson's diseases, or aging. Thus, it is expected that the study of apoptosis
      in the nervous system give us useful clues to know how the neuronal network are
      constructed in the development and why the neurodegenerative disease and brain
      aging occur.

PMID- 8154887
TI  - [Study of 5'-DFUR treatment as postoperative adjuvant chemotherapy for stomach
      and colorectal cancer. Tokai GATS Group (pilot study)].
AB  - In order to study preliminary the safety of 5'-DFUR treatment as postoperative
      adjuvant therapy, intermittent and continuous treatment regimens were
      administered to patients undergoing curative resection of carcinomas of the
      stomach and the colorectum. Two treatment schedules were employed: 5'-DFUR was
      either given continuously in a daily oral dose of 600 mg/patient (continuous
      group) or for 2 weeks in a daily oral dose of 1,200 mg/patient followed by 2
      weeks of no treatment (intermittent group). Twenty-one stomach cancer patients
      and 34 colorectal cancer patients were registered in the study. The rates of
      adverse drug reactions in the patients who completed treatment were 20.0% (2/10)
      in the continuous group and 50.0% (4/8) in the intermittent group of gastric
      cancer patients, and 16.6% (2/12) in the continuous group and 17.6% (3/17) in the
      intermittent group of colorectal cancer patients. The main adverse drug reactions
      were gastrointestinal symptoms. The incidence of diarrhea, a problematic side
      effect of 5'-DFUR, was 4.5% (1/22) in the continuous group and 12.0% (3/25) in
      the intermittent group. There were no statistically significant differences
      between the continuous group and the intermittent group in regard to the
      incidence of adverse drug reactions and survival rate. In addition, as there were
      no serious adverse drug reactions, both treatment regimens were demonstrated to
      be highly safe when administered as postoperative adjuvant therapy.

PMID- 8154888
TI  - [The effect of induction chemotherapy with CBDCA, 5-FU and UFT in head and neck
      cancer].
AB  - Induction chemotherapy of low-dose CBDCA, 120-hour continuous infusion 5-FU and
      UFT was applied to 22 patients with untreated head and neck cancer. CBDCA 75
      mg/m2 was given on day 1 and, subsequently, 5-FU 1,500 mg/m2/day for 120-hour
      continuous infusion was started. UFT was administered every day orally at 400-600
      mg/day as biochemical modulation. If tumors were reduced and side effects were
      mild, these schedules were repeated after two weeks. Three patients (14%)
      achieved a CR and 11 (50%) a PR, for an overall response rate of 64%. Anorexia,
      nausea, vomiting and stomatitis were the predominant toxicities. They were mild
      and well tolerable, although severe diarrhea was observed in one case. Good
      general conditions of patients were kept because of low grade of toxicities. They
      were important factors for the tolerance of subsequent radiotherapy and surgery.
      Based on these results, we conclude that the combination of low-dose CBDCA, 5-FU
      and UFT as biochemical modulation is effective in head and neck cancer.

PMID- 8154889
TI  - [Basic and clinical evaluation of the effect of pirarubicin against head and neck
      cancer--chemosensitivity test and a comparative study with doxorubicin].
AB  - The chemosensitivities of 77 samples of human head and neck cancer were examined
      by in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues
      obtained at biopsy specimens were exposed to doxorubicin (DXR) and pirarubicin
      (THP). The average decrease of the enzyme activity by THP was significantly
      greater than that by DXR. In 60 cases of squamous cell carcinomas, the
      chemosensitivity of poorly differentiated type tended to be higher compared to
      the well differentiated type. It is suggested from there results that THP is a
      more effective anticancer drug than DXR against human head and neck cancers.
      Clinically good responses were obtained in a systemic chemotherapy of such as
      head and neck adenoid cystic carcinomas by combining THP with other anticancer
      drugs such as CDDP (or CBDCA) and CPA.

PMID- 8154890
TI  - [A comparative study on the serum and tissue 5-FU concentrations in patients with
      hepatocellular carcinoma after preoperative oral administration of UFT and 5'
      DFUR].
AB  - UFT or 5'-DFUR was orally administered to the patients with hepatocellular
      carcinoma preoperatively and the concentrations of these drugs and 5-FU in the
      serum, liver tissue and cancer tissue obtained at the time of operation were
      measured. The unchanged 5'-DFUR was not detected in any of these samples. The
      concentration of 5-FU in cancer tissue was significantly higher in UFT treated
      group (0.409 microgram/g) than that in 5'-DFUR group (0.040 microgram/g).
      However, the 5-FU levels in the serum and noncancerous liver tissue were also
      higher than those in the patients with other organ cancers. Although UFT is a
      useful drug for the adjuvant chemotherapy of hepatocellular carcinoma, the dose
      was considered to be minimized to avoid the side effects since the activity of
      drug-metabolizing enzymes may be decreased in hepatocellular carcinoma
      complicated with liver cirrhosis.

PMID- 8154891
TI  - [The effect of suramin on human lung cancer cell line in vitro].
AB  - Recently, several investigators reported the effects of suramin, a drug used in
      the treatment of trypanosomiasis, onchocerciasis, and an inhibition of the
      binding of some growth factors to cell surface receptors. In present study,
      therefore, we examined the effects of epidermal growth factor(EGF) and suramin on
      cell proliferation and cell cycle kinetics of an established cell line from human
      lung cancer(PC-13). EGF showed a stimulatory effect on cell proliferation of PC
      13, suggesting EGF behaves as a growth factor of PC-13. On the other hand,
      suramin inhibited the stimulatory effect of EGF to PC-13 in a dose dependent
      manner. In addition, it was also observed that suramin inhibits the cell cycle
      progression from G0/G1 phase to S phase. These results indicate that suramin may
      withhold the cell proliferation and cell growth via suppression of the EGF cell
      stimulatory effects.

PMID- 8154892
TI  - [Evaluation of prognostic nutritional index (PNI) as a prognostic indicator in
      multimodal treatment for gynecological cancer patients].
AB  - We assessed the usefulness of PNI (PNI = 10 x serum albumin + 0.005 x peripheral
      lymphocytes) as a prognostic indicator and determinant of multimodal treatment
      for 30 gynecological patients (control group: 12 patients with gynecological
      benign disease; good prognostic group: 10 with more than two-year survival having
      gynecological cancer; poor prognostic group: 8 with less than one-year survival
      having gynecological cancer). It was concluded that 1) PNI of the poor prognostic
      group was significantly lower than that of good prognostic group and control
      group (p < 0.01); 2) PNI is effective as a prognostic indicator; and 3) PNI is
      useful in clinical practice as a determinant of the multimodal treatment and high
      risk group.

PMID- 8154893
TI  - [Cytofluorometric chase of the cancer cells after release from G2-block induced
      by peplomycin].
AB  - To study the alteration of nuclear DNA content of cancer cells after peplomycin
      (PEP) treatment, DNA cytofluorometry was performed in combination with 3H
      thymidine (3H-TdR) autoradiography using cultured A431 cells. The cells in the
      logarithmic growth were treated with PEP (1.25 micrograms/ml) for 24 hr, during
      the first 4 hr of which they were pulse-labeled with 3H-TdR (2.4 x 10(4) Bq/ml).
      After washing with PBS, the cells were then cultured without both PEP and 3H-TdR,
      fixed at different times and stained with propidium iodide (PI) for the auto
      stage cytofluorometry, which enabled DNA content analysis for labeled and
      unlabeled cells by repeated scanning of the same cell population. The nuclear DNA
      content histograms demonstrated that A431 cells were mostly arrested in G2 phase
      of 4C stem line by treatment with PEP for 24 hr. This G2 block lasted up to 8 hr
      after removal of the drug, and thereafter, marked polyploidization associated
      with DNA synthesis occurred, showing almost no mitotic figures, while only a few
      cells returned to G1 phase via M phase. During the period of 72-120 hr, however,
      the fractions of advanced polyploid cells (DNA content > or = 8C) gradually
      decreased and the DNA content distribution pattern became eventually similar to
      the original one as seen before PEP treatment. From these results we hypothesized
      as follows: 1) At S-G2 boundary, there is some control mechanism that checks
      whether the cells, after S phase, can enter the M phase or not. 2) The cells,
      which are not permitted to enter mitosis by the control mechanism, show marked
      polyploidization. 3) Only the cells that enter into mitosis can live and
      proliferate, though the advanced polyploid cells die shortly. 4) This control
      mechanism might be related to the precision of DNA repair that is checked at the
      G2-M checkpoint.

PMID- 8154894
TI  - [A case of a huge malignant lymphoma in the lesser omentum showing a long-term
      survival after combined treatment of surgery and VEP-THP chemotherapy].
AB  - A 33-year-old house wife with malignant lymphoma in the lesser omentum was
      treated with a combination of surgery and VEP-THP chemotherapy (consisting of
      pirarubicin, cyclophosphamide, fildesin and predonine). Complete remission has
      been observed by reduction surgery and subsequent chemotherapy of VEP-THP.
      Although mild bone marrow suppression was seen during the chemotherapy,
      gastrointestinal toxicity and alopecia were minimal, which led to 10 complete
      courses of VEP-THP regimen. The patient has been in good health 5 years after the
      operation with no sign of recurrence. This case indicates that even advanced
      malignant lymphoma may be successfully treated with a combination of surgery and
      proper chemotherapy.

PMID- 8154895
TI  - [Peritoneal dissemination of cecal cancer disappearing in a patient taking 5'
      DFUR for 3 years].
AB  - A 51-year-old woman presenting with a left ovarian tumor underwent left
      oophorectomy and hysterectomy with intraperitoneal administration of cisplatin,
      cyclophosphamide, and 5-fluorouracil on December 13, 1989. Microscopically the
      tumor was well-differentiated adenocarcinoma. Postoperatively cecal cancer was
      detected. Laparotomy revealed multiple peritoneal dissemination on March 23,
      1990, when palliative ileocecal resection was performed. Microscopy revealed
      several of the nodules to be adenocarcinoma and the cecal lesion well
      differentiated adenocarcinoma. The patient was then placed on 5'-deoxy-5
      fluorouridine (800 subsequently 600 mg/day). In November, 1991, bright red blood
      per rectum led to the discovery of rectal cancer. On January 26, 1993, laparotomy
      revealed rectal tumor invading the bladder but the metastatic nodules on the
      peritoneum had disappeared. Thus pelvic exenteration was performed. The tumor was
      well-differentiated adenocarcinoma. The ovarian lesion may have been a metastasis
      from the cecal cancer, a so-called Krukenberg tumor. The rectal cancer was most
      likely to be asynchronous cancer. 5'-DFUR seemed effective in remitting the
      peritoneal dissemination.

PMID- 8154896
TI  - [Successful inhibition of bladder tumor recurrence by oral administration of
      UFT].

PMID- 8154898
TI  - [Antitumor effect of camptothecin analog on liver metastatic model of human colon
      cancer in nude mice].

PMID- 8154897
TI  - [Experimental study on the anti-tumor effect of CDDP derivatives against the
      gastric cancer cell lines].

PMID- 8154899
TI  - [Irinotecan hydrochloride (CPT-11)].
AB  - Irinotecan hydrochloride (CPT-11) is a water-soluble semisynthetic derivative of
      camptothecin. CPT-11 is a prodrug that undergoes deesterification in vivo to
      produce SN-38, a metabolite that is 1,000-fold more potent than the parent
      compound in vitro. CPT-11 is a potent topoisomerase I inhibitor with a broad
      spectrum of experimental antitumor activity. Recent clinical trials also reveal
      that CPT-11 is very effective in the treatment of cancers including lung cancer,
      cervix cancer, ovary cancer, etc. Now, comparative trials of combination
      chemotherapy in responsive tumors are indicated from these excellent clinical
      results.

PMID- 8154900
TI  - [Interleukin-2 (IL-2)].
AB  - Interleukin-2, a polypeptide lymphokine that induces proliferation of antigen- or
      mitogen-stimulated T cells, was first described as "T-cell growth factor" by
      Morgan et al. in 1976. IL-2 is one of several lymphocyte-produced messenger
      regulatory molecules that modulate immunocyte function. The main secretory source
      of IL-2 is the T-helper cell. In 1983, Taniguchi and colleagues isolated a human
      IL-2 complementary DNA clone from a high-producer Jurkat leukemic cell line, and
      established its nucleotide sequence. In 1984, Rosenberg et al. described the
      isolation of cDNA clones of the gene for IL-2 from the Jurkat cell line, its
      expression in Escherichia coli and its biological characteristics. The mature
      secreted protein contains 133 amino acids, constituting a calculated molecular
      weight of 15,420. Since the discovery of IL-2 and its T-cell growth-promoting
      activity, extensive research has revealed the complex nature of its immunologic
      effects, both in vitro and in vivo. The immunopotentiating activities,
      encouraging in vitro results, plus successful therapy of animal tumors in
      preclinical studies provided the rationale for investigation of IL-2 in patients
      with advanced malignancy and immunodeficiencies. The IL-2 receptor has been found
      to have an unexpected by unusual structure in that it is composed of two separate
      chains designated alpha (p75) and beta (p55). Recently, it has been discovered
      the 3rd gamma-chain by Sugamura et al. Clinical trials of IL-2 in patients with
      cancer have been done by many researchers. The clinical trials has reviewed
      briefly.

PMID- 8154901
TI  - Clinical associations of prenatal ischaemic white matter injury.
AB  - Neuropathological examinations were carried out at necropsy on 274 cases of
      intrauterine death or neonatal death at or before three days after birth. Fifty
      six (20.4%) subjects had evidence of prenatal ischaemic brain damage. On review
      of the maternal case notes to ascertain antenatal clinical associations there was
      an increased incidence of intrauterine growth retardation, either based on birth
      weight for gestational age (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.1
      to 3.7) or diagnosed antenatally (OR 2.7; 95% CI 1.3 to 5.6). Oligohydramnios was
      also more common (OR 2.9; 95% CI 1.2 to 7.0). The association of intrauterine
      growth retardation and white matter damage remained after excluding fetuses with
      a major congenital anomaly (OR 2.4; 95% CI 1.1 to 5.1). The findings suggest that
      chronic intrauterine hypoxia may be associated with damage to cerebral white
      matter among fetuses and infants who die. The relation between ischaemic white
      matter damage and cerebral palsy among survivors remains speculative.

PMID- 8154902
TI  - Lipid peroxidation as a measure of oxygen free radical damage in the very low
      birthweight infant.
AB  - (ABSTRACTOxygen free radical mediated tissue injury is implicated as a major
      factor in the pathogenesis of the long term complications seen in the premature
      infant, and direct evidence of their role in the development of these long term
      problems is lacking. A prospective observational study of 78% of very low
      birthweight infants admitted to a level III neonatal intensive care unit in 1992
      was undertaken to determine the relationship between lipid peroxidation products,
      antioxidant activity, and outcome. Lipid peroxidation (malondialdehyde
      thiobarbituric acid, MDA-TBA) and antioxidant activity (vitamin E and glutathione
      peroxidase activity) were measured in 22 very low birthweight infants in the cord
      blood and the infant's blood at 24 hours, 48 hours, and 1 week of age and
      correlated with outcome measures. The normal range for these measures was
      established in the cord blood samples of 48 consecutive healthy full term
      infants. The concentration of MDA-TBA at 1 week correlated with the number of
      days of oxygen treatment and number of days of positive pressure ventilatory
      support. Controlling for gestational age and antenatal complications
      simultaneously the MDA-TBA concentration remained significantly associated with
      the number of days of oxygen treatment and the number of days of positive
      pressure ventilatory support. Glutathione peroxidase was low in the premature and
      full term infants consistent with the low concentrations of selenium known to be
      present in southern New Zealand. There was evidence of a quadratic relationship
      between vitamin E at 1 week and the total number of days of supplementary oxygen
      requirement, with both high and low values associated with increased oxygen
      requirement. This association, however, did not remain after controlling for
      gestational age and antenatal complications. These results support the role of
      oxygen free radicals in mediating tissue damage associated with the development
      of chronic lung disease in the premature infant.

PMID- 8154903
TI  - Re-evaluation of the left atrial to aortic root ratio as a marker of patent
      ductus arteriosus.
AB  - The aim of this study was to re-examine the accuracy of the left atrial aortic
      root ratio (LA:Ao) as a marker of significant patent ductus arteriosus (PDA) in
      the preterm infant by comparison with direct Doppler echocardiographic
      assessment. Fifty six infants (< 1500 g) had 463 serial echocardiograms. Firstly
      the LA:Ao was measured, then the duct was imaged and classified as wide open,
      restricting, or closed according to two dimensional and Doppler criteria.
      Probability analysis was performed to test the ability of the LA:Ao to
      discriminate between a wide open PDA and a restricting or closed duct. Mean LA:Ao
      was 1.17 and 1.21 when the duct was respectively closed or restricting compared
      with 1.61 when wide open. Using a LA:Ao of 1.5 as a cut off gives a sensitivity
      of 79% and specificity of 95% and increases the accuracy over the recommended
      levels of 1.3 and 1.4. With this cut off there were 20/94 false negatives, these
      were associated with scans on day 1 and large interatrial shunts. The sensitivity
      of the LA:Ao increased to 88% if only scans performed after day 1 were analysed.
      For diagnosing a PDA after day 1, the positive likelihood ratio of an LA:Ao of
      1.5 or more was 17.5, and the negative likelihood ratio of an LA:Ao < 1.5 was
      0.13. The LA:Ao is still a useful tool in the diagnosis of PDA. It is a simple
      method which needs less skill and resources than direct PDA imaging and is
      feasible on neonatal units without direct access to echocardiographic expertise.
      Its use on the first postnatal day is not recommended.

PMID- 8154904
TI  - Subclinical persisting pulmonary hypertension in chronic neonatal lung disease.
AB  - The development of pulmonary hypertension is one of the adverse factors in the
      outcome of infants with chronic neonatal lung disese (CNLD). The purpose of this
      cross sectional study was to evaluate the prevalence and degree of pulmonary
      hypertension in a cohort of survivors of CNLD stable in air. Pulmonary artery
      pressure was assessed using its inverse correlation with the ratio of time to
      peak velocity and right ventricular ejection time (TPV:RVET) as measured from
      Doppler velocity time signals in the main pulmonary artery. A normal ratio is >
      or = 0.35, a possibly low ratio lies between 0.31 and 0.35, and a definitely low
      ratio is < 0.31. The subjects were divided into three groups. Group A comprised
      58 infants with oxygen dependence and an abnormal chest radiograph at 28 days of
      age; group B comprised 18 infants with oxygen dependence and a normal chest
      radiograph at 28 days of age; and group C (controls) comprised 21 siblings
      without oxygen dependence by 10 days and a normal chest radiograph. There were
      significant differences in mean (SD) TPV:RVET ratio between group A 0.346
      (0.045), group B 0.335 (0.057), and groups A + B 0.344 (0.048) when compared with
      group C controls 0.385 (0.034). The prevalence of a definitely low TPV:RVET ratio
      suggesting a raised pulmonary artery pressure was 19% in group A, 39% in group B,
      24% in groups A + B, and none in group C. There were no clinical signs of
      pulmonary hypertension in any patient studied. Stepwise multiple linear
      regression failed to find significant associations with antenatal or neonatal
      putative risk factors. Additionally, there were no associations with childhood
      respiratory morbidity. These data suggest a high prevalence of subclinical
      pulmonary hypertension in CNLD patients. It is speculated that occult hypoxaemia
      may be occurring in this group of infants.

PMID- 8154906
TI  - Diet and faecal flora in the newborn: nucleotides.
AB  - Breast milk contains nucleotide salts that are only present in minimal amounts in
      modern infant formulas prepared from cows' milk. Nucleotides have been suggested
      as cofactors for the growth of bifidobacteria in vitro. Bifidobacteria are found
      to be more numerous in the faeces of breast fed babies compared with those of
      formula fed babies. Faecal flora were examined at 2 weeks of age in 32 babies who
      from birth had been fed a whey based formula supplemented with nucleotide
      monophosphate salts, 33 babies fed an unsupplemented formula, and 21 breast fed
      babies. Faecal flora were also examined at 4 weeks, and 7 weeks but with fewer
      babies in each group. Most differences were found at 2 weeks of age when more
      babies fed the nucleotide supplemented formula were colonised with Escherichia
      coli and more had E coli as the dominant organism in their faecal flora. Fewer of
      these babies were colonised with bifidobacteria. The counts of bifidobacteria and
      enterococci were reduced in the nucleotide supplemented group but bacteroides
      accounted for a higher percentage of the total flora in this group of babies.
      Supplementation of a formula with nucleotide salts did not make the faecal flora
      closer to that of breast fed infants as the growth of bifidobacteria was
      discouraged. While there may be arguments to support the addition of nucleotides
      to infant formula the results of this study do not support their addition for the
      enhancement of bifidobacteria in the faecal flora.

PMID- 8154905
TI  - Infantile hydrocephalus epidemiology: an indicator of enhanced survival.
AB  - The epidemiology of infantile hydrocephalus in the birth years 1973-90 was
      investigated in west Sweden. The study revealed a significant increase in
      prevalence from 1973-8 and 1979-82 considered due to the enhanced survival of
      very and extremely preterm infants. The increase did not continue from 1983-90.
      This could indicate an improved outcome in preterm survivors as the neonatal
      survival rate continued to increase. The striking predominance of a
      perinatal/neonatal aetiology in very preterm hydrocephalic infants could be
      confirmed: 89% born from 1983-90 had suffered a confirmed postpartum
      intraventricular haemorrhage. In infants born at term, prenatal origins, mainly
      maldevelopments, dominated. The outcome in very preterm surviving infants with
      infantile hydrocephalus was poor: 73% had cerebral palsy, 52% epilepsy, 22%
      severe visual disability, and 55% were mentally retarded. Despite the increased
      survival resulting in a majority of healthy infants, there is an accumulating
      cohort of hydrocephalic children.

PMID- 8154907
TI  - A randomised multicentre study of human milk versus formula and later development
      in preterm infants.
AB  - Whether breast milk influences later neurodevelopment has been explored in non
      randomised studies, potentially confounded by social and demographic differences
      between feed groups. Here in a strictly randomised prospective multicentre trial,
      Bayley psychomotor and mental development indices (PDI and MDI) were assessed at
      18 months postterm in survivors of 502 preterm infants assigned to receive,
      during their early weeks, mature donor breast milk or a preterm formula. These
      diets were compared as sole enteral feeds or as supplements to the mother's
      expressed breast milk. No differences in outcome at 18 months were seen between
      the two diet groups despite the low nutrient content of donor milk in relation to
      the preterm formula and to the estimated needs of preterm infants. These results
      contrast with those reported from our parallel two centre study that compared
      infants randomly assigned a standard term formula or the preterm formula during
      their early weeks; those fed standard formula, now regarded as nutritionally
      insufficient for preterm infants, were substantially disadvantaged in PDI and MDI
      at 18 months post-term. It is shown here that infants from that study fed solely
      on standard formula had significantly lower developmental scores at 18 months
      than those fed on donor breast milk in the present study; yet the standard
      formula had a higher nutrient content than the donor milk. Thus, donor milk
      feeding was associated with advantages for later development that may have offset
      any potentially deleterious effects of its low nutrient content for preterm
      infants. As these outcome advantages were not confounded by the social and
      educational biases usually associated with mothers' choice to breast feed, our
      data add significant support to the view that breast milk promotes
      neurodevelopment.

PMID- 8154908
TI  - Diagnosis and management of non-immune hydrops in the newborn.

PMID- 8154909
TI  - Professor Charles D Meigs (1792-1869) of Philadelphia and persistent fetal
      circulation.

PMID- 8154910
TI  - Randomised trial of methods of extubation in acute and chronic respiratory
      distress.

PMID- 8154911
TI  - Varicella zoster virus infection in pregnancy.

PMID- 8154912
TI  - Echocardiographic assessment of cardiac function in shocked very low birthweight
      infants.

PMID- 8154913
TI  - Changes in cerebral artery blood flow velocity after intermittent cerebrospinal
      fluid drainage.

PMID- 8154914
TI  - Congenital diaphragmatic hernia: influence of associated malformations on
      survival.

PMID- 8154915
TI  - Maternal carboxyhaemoglobinaemia.

PMID- 8154916
TI  - Ureaplasma and mycoplasma central nervous system infections in neonates.

PMID- 8154917
TI  - Doppler and fetal growth retardation.

PMID- 8154918
TI  - Extracorporeal membrane oxygenation.

PMID- 8154919
TI  - Neonatal outcome after pregnancy complicated by abnormal velocity waveforms in
      the umbilical artery.
AB  - The neonatal outcome of 61 infants born after pregnancies complicated by absent
      or reversed end diastolic flow velocities (AREDFV) in the fetal umbilical artery
      was compared with that of 61 controls matched for gestational age born after high
      risk pregnancies with documented forward end diastolic flow velocities (EDFV).
      The AREDFV group was significantly more growth retarded, had lower platelet
      counts at birth, and were more likely to become significantly thrombocytopenic in
      the first week after birth. Owing to concerns about the possible increased risk
      of necrotising enterocolitis in newborn infants after AREDFV, this group was
      started on enteral feeds later and was more likely to receive parenteral
      nutrition than the EDFV group. Seven infants with AREDFV and one control infant
      developed necrotising enterocolitis.

PMID- 8154920
TI  - Hypoxic ventilatory defence in very preterm infants: attenuation after long term
      oxygen treatment.
AB  - The activity of peripheral chemoreceptors was studied in 19 preterm very low
      birthweight infants at the postconceptional age of 36 and 40 weeks using the
      hyperoxic test. The infants were in a healthy condition and did not receive any
      extra oxygen or medication when tested. The inhalation of pure oxygen caused a
      decrease in mean (SE) ventilation by 16.1 (2.6)% and 15.1 (2.1)% at the 36th and
      40th gestational week respectively. At the 36th gestational week the ventilatory
      response was significantly slower than at 40 weeks (10.9 (6) and 7.3 (3) sec).
      Six infants who had been on supplemental oxygen for more than 21 days (from 21 to
      56 days) responded with significantly lower response to hyperoxia at the 36th
      gestational week (-7.9 (3.6)%) than those receiving oxygen treatment for a
      shorter period of time, 0 to 16 days (-19.9 (3.2)%). The 'low responding' group
      included three infants who had suffered from chronic lung disease. Those infants
      showed the lowest hyperoxic response (-4.3 (3.9)%). There was no difference in
      the response among healthy preterm infants (eight infants) and infants with
      respiratory distress syndrome. At the 40th gestational week the differences, even
      though showing the same characteristics, were not statistically significant. No
      statistically significant relationship was found between the strength of the
      ventilatory response to oxygen versus gestational, postnatal age, nor the time
      interval between the termination of supplemental oxygen treatment and the test.
      No relationship was found between the number of apnoeic/bradycardic spells and
      the strength of the ventilatory depression caused by hyperoxia. In conclusion we
      found that the very preterm infants, with the exception of those who received
      long periods of oxygen treatment, have stronger peripheral chemoreceptor
      responses than those reported for 2-4 day old full term infants. However, infants
      who had suffered from chronic lung disease show a depressed hyperoxic response.

PMID- 8154921
TI  - Comparison of mortality and rates of cerebral palsy in two populations of very
      low birthweight infants.
AB  - Comparisons of mortality and rates of cerebral palsy in different populations can
      be confusing. This is illustrated by comparing two populations of very low
      birthweight infants born in the 1980s, one from the Netherlands, the other from
      the UK (Oxford region). Although a number of biases were controlled for while
      comparing two large geographically defined populations, by assessing the
      survivors at similar ages and describing their health status in a standard way,
      some problems in interpretation of outcome remained. Differences in registration
      practice of live births at early gestational ages, as well as differences in
      withholding or withdrawing treatment, which occurred in about half of the cases
      of neonatal death in the Netherlands and in about one third of those in the
      Oxford region, may have influenced the incidence of registered live births,
      neonatal mortality, and the rate of cerebral palsy.

PMID- 8154922
TI  - Influence of oral isotretinoin on hepatic and cutaneous P-450-dependent isozyme
      activities.
AB  - Oral administration of isotretinoin (13-cis-retinoic acid) (6 mg/kg per day),
      0.05% hexachlorobenzene (HCB) or both drugs simultaneously for 10 days to female
      Wistar rats caused a statistically significant induction of aminopyrine-N
      demethylase (ADM), 7-ethoxyresorufin-O-deethylase (7-ERO-D) and erythromycin-N
      demethylase (EMDM) in the liver microsomes. Oral administration of isotretinoin
      alone or together with HCB induced a marked induction of 7-ERO-D and EMDM in the
      skin. Administration of isotretinoin alone for 60 days resulted in the induction
      of EMDM in the liver microsomes, and in combination with HCB caused a
      statistically significant induction of all hepatic isozymes. HCB alone caused a
      marked induction of only 7-ERO-D in the skin. These results clearly show that
      oral isotretinoin is capable of inducing hepatic and cutaneous microsomal P-450
      dependent catalytic activities. It remains to be elucidated whether the induction
      of these enzymes is of importance for the therapeutic action of isotretinoin.

PMID- 8154923
TI  - Improvement of epidermal differentiation and barrier function in reconstructed
      human skin after grafting onto athymic nude mice.
AB  - To determine whether epidermis reconstructed in vitro at the air-liquid interface
      on de-epidermized dermis has the capacity to normalize the expression of
      differentiation-specific markers, its lipid composition and stratum corneum
      barrier properties, human skin equivalents were transplanted onto athymic nude
      mice and investigated at different stages ranging from 1 to 4 months after
      grafting. Indirect immunofluorescence with species- or non-species-specific
      antibodies revealed that as early as 1 month after transplantation
      keratinization, and involucrin, loricrin and transglutaminase patterns were
      normalized. Human melanocytes were observed in the basal layer of the pigmented
      graft. As revealed by high-performance thin-layer chromatography and transmission
      electron microscopy after ruthenium tetroxide fixation, the lipid profile and the
      intracellular lamellar organization were similar to those found in natural
      epidermis. Transepidermal water loss measurements and penetration studies showed
      that the barrier properties of the reconstructed epidermis after transplantation
      were comparable to those of normal human skin.

PMID- 8154924
TI  - The growth and differentiation of human keratinocytes in vitro: a combined
      immunohistochemical and flow cytometric study.
AB  - In this study we performed a cell kinetic characterization of the growth and
      differentiation of human keratinocytes. Using a combination of
      immunohistochemical and flow cytometric techniques it was possible to obtain a
      detailed description of these processes. The proliferative activity of the cell
      cultures was analysed with flow cytometric techniques, measuring relative DNA
      content, iododeoxyuridine incorporation and the expression of the antigen
      recognized by Ki-67. In addition to a standard monolayer culture technique, cells
      were maintained in suspension. Under these conditions these cells were not
      capable of dividing, started to lose their nuclei, and the expression of
      differentiation-related proteins such as involucrin and filaggrin was induced,
      suggesting that the cells changed towards a differentiated phenotype. Binding of
      the antibody Ks8.12, recognizing keratins 13 and 16, occurred under all culture
      conditions, independent of cell density, and also in suspension, suggesting that
      it is a marker for abnormal differentiation rather than for hyperproliferation.

PMID- 8154925
TI  - Intracellular free calcium and growth changes in single human keratinocytes in
      response to vitamin D and five 20-epi-analogues.
AB  - Vitamin D, 1,25(OH)2D3, decreases proliferation and promotes differentiation of
      keratinocytes, and other keratinocyte differentiation stimuli have been
      associated with an early rise in intracellular free calcium, [Ca2+]i. We
      therefore investigated the effect of 1,25(OH)2D3, its precursor D3 and five 20
      epi-analogues (EB1089, KH1060, KH1139, MC1288, MC1301) on growth and [Ca2+]i
      levels of normal human keratinocytes. Cells were cultured in medium MCDB153 with
      an extracellular calcium concentration of 70 microM or 1 mM. All the analogues
      were more potent than 1,25(OH)2D3 at inducing the morphological changes of
      differentiation, but D3 was inactive. At concentrations down to 10(-8) M
      1,25(OH)2D3, caused significant inhibition of growth, as assessed by counting
      cells and measurement of thymidine labelling. At 5 days 50% inhibition of growth
      occurred with 64 nM 1,25(OH)2D3 and 3330 nM D3. All the analogues were more
      potent than 1,25(OH)2D3, and KH1060 inhibited growth at 10(-10) M. In single
      keratinocytes [Ca2+]i was measured by microspectrofluorimetric techniques using
      the dye fura-2. No immediate rise in [Ca2+]i was observed following addition of
      1,25(OH)2D3 or the analogues up to 10(-6) M. However 10(-7) M 1,25(OH)2D3 or the
      analogues induced a gradual increase in [Ca2+]i, significant at 4 h (P < 0.001),
      which increased further over 2-3 days. D3 had no effect on [Ca2+]i. Increases in
      [Ca2+]i following the differentiation stimuli of either 2 mM extracellular
      calcium or 1,25(OH)2D3 were similar at 48 h, increasing from 100 +/- 3 nM (mean
      +/- SEM) in control cells to 150 +/- 3 nM with 2 mM calcium and 144 +/- 6 nM with
      10(-7) M 1,25(OH)2D3. The effect of extracellular calcium in raising [Ca2+]i
      within minutes was more rapid than 1,25(OH)2D3, but in combination the two were
      not additive.

PMID- 8154926
TI  - Selective loss of chondroitin 6-sulphate from basement membrane during
      progression from actinic keratosis to squamous cell carcinoma.

PMID- 8154927
TI  - Influence of various cytokines on the interleukin-2-dependent lysis of melanoma
      cells in vitro.
AB  - To obtain information about useful combinations of various cytokines in melanoma
      therapy, we studied the influence of interleukin-2 (IL-2) in combination with
      interferon-alpha (IFN-alpha), IFN-gamma and tumour necrosis factor-alpha (TNF
      alpha) on the lytic activity of IL-2-stimulated cells in vitro. Peripheral
      mononuclear cells (PMC) were incubated for 4 days with various combinations of
      cytokines and used as effector cells. Two different melanoma cell lines (M19 and
      M26) were used as target cells. The lytic activity of stimulated PMC was
      determined using a modified hexosaminidase assay. IL-2 was mainly responsible for
      the lytic activity of the effector cells in a dose-dependent manner. IFN-alpha,
      IFN-gamma and TNF-alpha did not enhance lytic activity with an optimal IL-2 dose
      (50 IU/ml IL-2). Using a suboptimal IL-2 dose (5 IU/ml), they increased
      cytotoxicity. The specific lysis of M19 cells was significantly increased by
      pretreatment of the cells with 5 IU/ml IFN-alpha together with 50 IU/ml TNF-alpha
      (t-test, P < or = 0.001), while the specific lysis of M26 cells was increased by
      pretreatment with 5 IU/ml IFN-gamma. We conclude that the lysis of melanoma cells
      by cytotoxic cells in vitro can be enhanced by various cytokines. The optimal
      cytokine combination differed for the two melanoma cell lines tested.

PMID- 8154928
TI  - Serum concentration of procollagen type I carboxyterminal propeptide in systemic
      sclerosis.
AB  - The serum level of procollagen type I carboxyterminal propeptide (P1CP), which
      has been used as an index of collagen synthesis in patients with various fibrotic
      diseases during the active stage, was measured using enzyme-linked immunosorbent
      assay in 61 patients with systemic sclerosis (SSc) and in 21 control subjects.
      The mean P1CP level in the SSc patients was significantly higher than in the
      normal controls (mean +/- SD, 326 +/- 319 vs 128 +/- 87 ng/ml; p < 0.005). In 36%
      of the SSc patients, the serum P1CP level was significantly elevated more than
      two standard deviations above the mean control value. The mean serum P1CP level
      in patients with diffuse SSc was significantly higher than in those with limited
      SSc (411 +/- 373 vs 255 +/- 199 ng/ml; p < 0.05). In addition, the SSc patients
      with elevated serum P1CP levels showed a significantly greater incidence of lung
      fibrosis and joint involvement than those with normal P1CP levels (p < 0.005 and
      p < 0.05, respectively). These results suggest that the serum P1CP level is a
      useful indicator of the severity of disease in SSc patients.

PMID- 8154929
TI  - Catechol-O-methyltransferase in vitiligo.
AB  - Catechol-O-methyltransferase (COMT) is involved in the metabolism of
      neurotransmitters such as epinephrine, norepinephrine and dopamine. For
      melanocytes, the enzyme is of particular importance in preventing the formation
      of toxic o-quinones during melanin synthesis. It has been suggested that COMT
      plays a regulatory role in melanin synthesis. Indeed, when the melanin precursor
      molecule DHI(2C) is methylated by COMT it is no longer available for
      incorporation into melanin. Auto-destruction by intermediates of melanin
      metabolism has been implicated in the aetiology of vitiligo. Therefore enzyme
      activities in vitiligo patients and in healthy controls were compared. Systemic
      COMT activities were measured using red blood cells (RBC) as starting material.
      However, as local alterations in COMT activity may be specifically involved in
      vitiligo, the enzyme activity was also measured in epidermal homogenates.
      Finally, to ascribe epidermal COMT activity to the responsible cell type(s),
      enzyme activity was measured in cultured vitiligo non-lesional melanocytes and
      melanocytes from healthy controls as well as in cultured keratinocytes from
      lesional skin and in purified keratinocytes from control skin. It was found that
      epidermal homogenates from vitiligo patients expressed higher levels of COMT
      activity than homogenates from healthy controls. Such differences were not found
      at the systemic level (i.e. in RBC) nor could they be explained by measurements
      on separately cultured epidermal cell types, indicating that the COMT activity
      was induced at the tissue level by extracellular factors.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8154930
TI  - Hydroperoxides in oxidized d-limonene identified as potent contact allergens.
AB  - Hydroperoxides of d-limonene were shown to be potent contact allergens when
      studied in guinea-pigs. Limonene-2-hydroperoxide (2-hydroperoxy-p-mentha-6,8
      diene, a mixture of trans and cis isomers) was synthesized for the first time.
      The ratio between the trans and cis forms was 3:1. These two hydroperoxides were
      identified as the major hydroperoxides in autoxidized d-limonene. In photo
      oxidized d-limonene, they constituted a minor part of the hydroperoxide fraction.
      Hydroperoxides may bind to proteins of the skin to make antigens either via a
      radical mechanism or after reactions to give epoxides. The cross-reactivity
      between the epoxide limonene-1,2-oxide, a potent contact allergen, and the
      hydroperoxides was therefore studied. No significant pattern of cross-reactivity
      was found. Further studies to identify and test the allergenicity of single
      hydroperoxides are needed to elucidate the mechanism of the allergenicity.

PMID- 8154931
TI  - The relationship between osteoarthritis and osteoporosis in the general
      population: the Chingford Study.
AB  - OBJECTIVE: A total of 979 women from the Chingford general population survey were
      studied to examine the hypothesis that osteoarthritis (OA) and osteoporosis are
      inversely related. METHODS: All women had radiographs of the hands and knees. A
      total of 579 also had AP radiographs of the lumbar spine which were graded for
      the presence of osteophytes. All women had bone densitometry performed at the
      lumbar spine (L1-L4) and femoral neck. Mean bone densities (BMD) were compared
      between those with disease and those with no disease at any other sites. All
      results were adjusted for age and body mass index (BMI). RESULTS: All OA groups
      had significantly higher bone density than controls at the lumbar spine. For
      distal interphalangeal (DIP) OA (n = 140) the difference was +5.8% (+3.0, +8.6),
      for carpometacarpal (CMC) OA (n = 160) +3.0% (+0.1, +5.9), for knee OA (n = 118)
      +7.6% (+4.3, +10.9), and lumbar spine OA (LSOA) (n = 194) +7.8% (+6.0, +8.8).
      Those with generalised OA (GOA n = 22), a combination of knee, DIP and CMC OA had
      an increase of +9.3 (+2.0, +16.6). For the femoral neck BMD was also increased
      significantly ranging from +2.5% for the CMC, +6.2% for the knee and +6.3% in the
      lumbar spine OA group. The risk of knee OA for women in the top tertile of BMD
      was 2.13 (1.15-3.93). Additional adjustment for other confounders such as
      smoking, alcohol, exercise, HRT, social class and spine osteophytes did not alter
      the results. CONCLUSIONS: These results suggest that small increases in BMD are
      present in middle aged women with early radiological OA of the hands, knees and
      lumbar spine. These data support the hypothesis that the two conditions are
      inversely related, although the mechanisms remain unclear.

PMID- 8154932
TI  - Bone turnover in non-steroid treated rheumatoid arthritis.
AB  - OBJECTIVE: To examine whether changes in cancellous bone turnover and resorption
      cavity depth contribute to bone loss in patients with non-steroid treated
      rheumatoid arthritis. METHODS: Iliac crest biopsies were obtained from 37
      patients with non-steroid treated rheumatoid arthritis, 13 male and 24 female,
      aged 37-71 years. Bone turnover and resorption cavity characteristics were
      quantitatively assessed using semiautomated computerised techniques. RESULTS:
      When compared with age- and sex-matched control values, there was a significant
      reduction in bone formation rate at tissue level and activation frequency (P <
      0.001) in the patient group. The eroded perimeter, mean and maximum eroded depth
      and cavity area were also significantly reduced (P < 0.01, < 0.005, < 0.01 and <
      0.005 respectively). CONCLUSION: These results demonstrate low bone turnover in
      non-steroid treated rheumatoid arthritis and indicate that the reduced bone mass
      in these patients is due mainly to a negative remodelling balance.

PMID- 8154933
TI  - Abnormal haem biosynthesis in the chronic anaemia of rheumatoid arthritis.
AB  - OBJECTIVES: The chronic microcytic anaemia of rheumatoid arthritis (RA) occurs
      despite the presence of adequate reticulo-endothelial iron stores. The red cell
      microcytosis is evidence of impaired haemoglobin production. This study has
      examined possible abnormalities of erythroid haem biosynthesis that may
      contribute to the anaemia. METHODS: 5-Aminolaevulinate (ALA) synthase and
      ferrochelatase activities were assayed in whole bone marrow and in purified
      erythroblasts from patients with RA and in control subjects. All patients were
      iron replete with demonstrable iron in the bone marrow. RESULTS: ALA synthase
      activity was significantly reduced in both whole bone marrow and purified
      erythroblasts from patients with the anaemia of RA. Erythrocyte protoporphyrin
      levels were raised in nine of 12 patients tested while ferrochelatase activity
      was normal. CONCLUSION: These abnormalities provide absolute evidence of abnormal
      erythroblast haem biosynthesis and iron metabolism in the anaemia of RA and most
      likely reflect decreased ALA synthase mRNA translation and some abnormality of
      erythroblast iron transport. Further studies using highly purified erythroblast
      populations will attempt to identify the causal factors leading to this abnormal
      erythroblast metabolism.

PMID- 8154934
TI  - Lymphocyte responses to DR1/4 restricted peptides in rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether analog and unrelated DR1/4 binding peptides alter
      DR1/4 restricted responses of peripheral blood lymphocytes (PBL) from patients
      with rheumatoid arthritis (RA). METHODS: PBL from 25 patients with RA and 12
      healthy controls were cultured with DR1/4 restricted peptides of the influenza
      haemagglutinin, amino acids 307-319 (HA) and matrix proteins, amino acids 17-29
      (IM). Responses were determined by 3H-thymidine uptake proliferation assays and
      limiting dilution analysis. Competitor peptides were analogs HA-R312 and HA-K313
      differing from HA by one amino acid at the 312 or 313 position respectively or
      unrelated peptides which bind to DR1/4. RESULTS: The responses of eight patients
      with RA to the two stimulatory influenza peptides did not differ significantly
      from controls and this was confirmed by the frequency estimate of T cells in PBL
      which responded to HA (mean frequency: 1 in 9.0 x 10(4), n = 5, in DR1/4+ RA
      patients, 1 in 7.6 x 10(4), n = 5, in DR1/4+ healthy controls). DR1/4 binding
      analogs of the HA peptide inhibited HA specific peptide responses of PBL from
      patients with RA and controls. Inhibition was also detected with unrelated
      peptides which bind to DR1/4 but to which the individual did not respond.
      CONCLUSION: Similar responses to two DR1/4 restricted peptides were observed in
      patients with RA and controls. Both antigen analog- and unrelated peptide-major
      histocompatibility complexes (MHC) can result in the inhibition of antigen
      specific responses in multi-clonal human lymphocyte populations. However, an
      analog peptide may be stimulatory in some individuals. These results provide some
      initial data for the development of a rational approach to MHC-specific
      immunomodulation in rheumatoid arthritis.

PMID- 8154935
TI  - Muscle biopsy abnormalities in systemic lupus erythematosus: correlation with
      clinical and laboratory parameters.
AB  - OBJECTIVES: To investigate the incidence and significance of Type II fibre
      atrophy, vessel wall thickening, lymphocytic vasculitis and myositis in needle
      quadriceps muscle biopsies from patients with systemic lupus erythematosus (SLE)
      and their correlations with clinical and laboratory parameters. METHODS: Needle
      quadriceps muscle biopsies from 55 patients with SLE and 26 controls were
      prospectively examined. Clinical and laboratory parameters recorded at the time
      of muscle biopsy included arthralgia, arthritis, myalgia, proximal weakness,
      vasculitic rashes, Schirmer test, ENA antibodies, ESR, serum creatine kinase (CK)
      and plasma C3 degradation products. RESULTS: Abnormal muscle biopsies were
      significantly more frequent in patients with SLE compared with controls (P <
      0.005). None of the controls had lymphocytic vasculitis and/or myositis. The
      difference in incidence between patients with SLE and controls for lymphocytic
      vasculitis was significant at P < 0.005. Due to the small number of SLE patients
      with myositis, the difference in incidence for this abnormal finding reached only
      P = 0.09. In the SLE patient group, lymphocytic vasculitis was associated with
      significantly higher ESR values (P = 0.007) and higher incidence of arthritis (P
      = 0.01); and appears to characterise a subset of patients with positive Schirmer
      tests, anti-Ro and/or anti-La antibodies. Raised serum CK was found to correspond
      with underlying myositis in patients with SLE and these patients also had an
      increased incidence of symptoms of proximal weakness and/or anti-RNP antibodies.
      In contrast, both Type II fibre atrophy and vessel wall thickening failed to
      correlate with any of the clinical and laboratory parameters studied and appear
      to be non-specific findings. CONCLUSIONS: Abnormal muscle biopsies are common in
      patients with SLE and the presence of lymphocytic vasculitis and/or myositis
      signify pathology in these patients. Histopathological abnormalities in needle
      quadriceps muscle biopsies are further valuable parameters in the assessment of
      patients with SLE.

PMID- 8154936
TI  - Mycoplasmas and ureaplasmas in patients with hypogammaglobulinaemia and their
      role in arthritis: microbiological observations over twenty years.
AB  - OBJECTIVES: To study the occurrence of mycoplasmas and ureaplasmas in patients
      with hypogammaglobulinaemia and the relationship of these micro-organisms to
      septic arthritis. METHODS: Over a period of about 20 years, 53 men and 38 women
      with hypogammaglobulinaemia, most of whom were less than 50 years old, were
      examined clinically and microbiologically. Mycoplasmas and ureaplasmas were
      sought in the throat, urogenital tract and joints by standard cultural methods,
      although not consistently in the three sites of all patients. RESULTS: Arginine
      hydrolysing mycoplasmas and ureaplasmas occurred with similar frequency in the
      sputum/throat of the hypogammaglobulinaemic patients, but no more often than
      might be expected in immunocompetent patients. Ureaplasmas, however, dominated in
      the urogenital tracts of both men and women, being found in 75% of vaginal
      specimens. Arginine-hydrolysing mycoplasmas occurred two to six times more
      frequently and ureaplasmas two to three times more frequently in urine specimens
      from hypogammaglobulinaemic patients than they did in such specimens from sex-
      and age-matched non-venereal disease, hospital patients or healthy subjects;
      these differences were statistically significant (p < 0.05). Enhanced mucosal
      colonisation probably increases the chance of spread to distant sites, such as
      the joints. Of the 91 patients, 21 (23%) had septic arthritis involving one or
      more joints. Mycoplasmas and/or ureaplasmas, but not bacteria, were isolated from
      the joints of eight (38%) of these patients. However, dissemination to joints
      apparently had not occurred in some despite the opportunity by virtue of
      mycoplasmal or ureaplasmal colonisation at a mucosal site. Sometimes antibiotic
      therapy failed clinically, and microbiologically and recommendations for
      management are outlined. CONCLUSIONS: Hypogammaglobulinaemic patients appear to
      be more susceptible to colonisation of mucous membranes, especially of the
      urogenital tract, with mycoplasmas and ureaplasmas than are immunocompetent
      individuals. These micro-organisms are responsible for about two fifths of the
      septic arthritides occurring in these patients.

PMID- 8154937
TI  - HLA-DP does not contribute towards susceptibility to systemic lupus
      erythematosus.
AB  - OBJECTIVES: To determine whether HLA-DP genes are involved in determining
      susceptibility to systemic lupus erythematosus (SLE). METHODS: HLA-DPA1 and DPB1
      genes were amplified by PCR of DNA samples from a panel of patients with SLE and
      normal controls. Amplified DNA was blotted on to nylon filters and probed with
      sequence-specific oligonucleotide (SSO) probes. RESULTS: No DPA1 or DPB1 allele
      was significantly associated with SLE, or with any immunological or clinical
      subset of SLE. Evidence was found for only limited linkage disequilibrium between
      HLA-DP and HLA-DQ/DR variants, and none between HLA-DP and the TAP2 gene.
      CONCLUSIONS: These data indicate that HLA-DP genes do not contribute towards
      determining susceptibility to SLE.

PMID- 8154938
TI  - Anti-laminin autoantibodies in collagen vascular diseases: the use of adequate
      controls in studies of autoimmune responses to laminin.
AB  - OBJECTIVES: To determine the significance of anti-laminin antibodies in patients
      with collagen vascular diseases using a large control population of normal
      individuals. METHODS: Anti-laminin antibodies of IgG isotypes were determined
      using an ELISA assay in a population consisting of 73 patients with systemic
      sclerosis, 10 with urticarial vasculitis, five with leukocytoclastic vasculitis,
      13 with giant cell arteritis, and eight with dermatomyositis. Sera from 134
      healthy individuals served as controls. RESULTS: Only eight sera in the systemic
      sclerosis group, one in the leukocytoclastic group and one in the giant cell
      arteritis group were abnormal. No other sera were abnormal. CONCLUSION: These
      data contradict previous studies using smaller numbers of controls. The necessity
      for an adequate control population to define abnormal when comparing immune
      responses among groups is frequently under-emphasised in rheumatological studies.

PMID- 8154939
TI  - Silicone breast prostheses and rheumatic symptoms: a retrospective follow up
      study.
AB  - OBJECTIVES: To determine whether women with silicone breast prostheses have more
      rheumatic complaints than controls. METHODS: The study included 287 women who had
      silicone breast prostheses implanted between 1978-90. For every patient a female
      control of the same age was selected who had had an aesthetic operation in the
      same year. A questionnaire was sent to this retrospective cohort of women with
      silicone breast prostheses and controls. RESULTS: Questionnaires were returned by
      235 cases (82%) and 210 controls (73%). Patients reported more symptoms arising
      after surgery than controls (0.6 v 0.3 complaints per subject, p < 0.001). The
      average interval between surgery and onset of complaints was 5.1 years for
      patients and 5.9 for controls. Complaints presented by patients were: painful
      joints (p < 0.005), burning eyes (p < 0.01), and skin abnormalities (p < 0.005).
      Differences in the use of antirheumatic drugs or medical consultations related to
      rheumatic symptoms did not reach statistical significance. Further information
      obtained from the patients and controls reporting rheumatic symptoms did not
      reveal the presence of a specific syndrome in connection with silicone materials.
      CONCLUSION: Women with silicone breast prostheses report more rheumatic
      complaints after silicone implantation than controls, but there is no evidence of
      increased prevalence of common rheumatic diseases.

PMID- 8154940
TI  - Arthritogenic potential of the 65 kDa stress protein--an experimental model.
AB  - OBJECTIVES: To assess the effect of an intra-articular presentation of stress
      (heat shock) proteins (hsp) on joint inflammation. METHODS: Wistar rats were
      sensitised with a suspension of heat killed Mycobacterium tuberculosis in oil in
      the scruff of the neck and challenged intra-articularly with stress protein or M
      tuberculosis preparations. Inflammation was assessed by joint swelling and, using
      immunohistology, cellular infiltration of the synovium and antibody induction by
      an enzyme-linked immunosorbent method. RESULTS: It was shown, for the first time,
      that the intra-articular administration of a recombinant myobacterial 65 kDa hsp
      can induce joint inflammation in M tuberculosis sensitised recipients; both
      powdered M tuberculosis and the purified protein derivative of tuberculin (PPD)
      produced a similar response, with T cell infiltration of the synovium and a time
      course typical of delayed type hypersensitivity. This response was specific to
      the 65 kDa protein as another immunodominant mycobacterial stress protein of 10
      kDa was ineffective. Furthermore, intra-articular injection of the 65 kDa hsp
      induced an antibody response against both the 65 kDa and 10 kDa proteins and the
      antibody titres continued to rise when knee swelling had subsided. CONCLUSIONS:
      These results support the hypothesis that 60 kDa proteins are a relevant
      arthritogenic stimulus in an M tuberculosis background. Moreover, when antigen
      presentation occurs in the synovium of previously sensitised individuals,
      circulating antibodies are generated which persist and recognise cross-reactive
      epitopes on several stress proteins.

PMID- 8154941
TI  - Liver disease in twins with Felty's syndrome.

PMID- 8154942
TI  - Pseudoarthrosis in ankylosing spondylitis.

PMID- 8154943
TI  - Debrisoquine oxidation polymorphism in patients with rheumatoid arthritis.

PMID- 8154944
TI  - A controlled trial of the effect of topical glyceryl trinitrate on skin blood
      flow and skin elasticity in scleroderma.

PMID- 8154945
TI  - Osteoporosis and Ehlers-Danlos syndrome.

PMID- 8154946
TI  - Brother and sister with myeloperoxidase associated autoimmune disease.

PMID- 8154947
TI  - Clinical issues of blood cultures.

PMID- 8154948
TI  - Prevalence of distal colonic neoplasia associated with proximal colon cancers.
AB  - BACKGROUND: The number, size, and histologic features of distal colorectal
      adenomatous polyps have been reported to correlate with the risk of developing
      proximal colon cancer. To investigate this putative relationship further, we
      evaluated the frequency of distal colorectal neoplastic polyps in patients with
      colon cancer located proximal to the splenic flexure. METHODS: All cases of
      colorectal adenocarcinomas treated at a tertiary referral center and Veterans
      Affairs hospital between 1979 and 1992 were identified by International
      Classification of Diseases coding and review of pathology and colonoscopy
      reports. The medical records of patients with documented cancers proximal to the
      splenic flexure were examined for the presence, location, size, and
      histopathologic features of synchronous neoplastic lesions found at colonoscopy.
      RESULTS: Among 634 patients with colorectal cancer identifiable by location, 172
      had proximally located tumors. Of these, 60 patients were excluded because of
      lack of complete colonoscopy or because surgical resection was performed
      elsewhere. Forty percent of the remaining 112 patients for whom data could be
      evaluated demonstrated neoplastic lesions in addition to the proximal cancer. The
      colon was devoid of "sentinel" neoplasia distal to the splenic flexure and
      descending colon-sigmoid colon junction in 69% and 72% of patients, respectively.
      CONCLUSIONS: The majority of proximal colon cancers are not associated with
      distal sentinel lesions. We surmise that flexible sigmoidoscopy will fail to find
      evidence of neoplasia in at least 25% of patients with prevalent colon cancers.

PMID- 8154949
TI  - The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in
      the elderly.
AB  - BACKGROUND: There are no studies that define the basic epidemiology of pulmonary
      embolism (PE) and deep venous thrombosis (DVT) in the elderly. This project was
      undertaken to provide that information. METHODS: We obtained all Medicare claims
      during the period 1986 through 1989 from a random 5% sample of US Medicare
      enrollees. By selecting codes used for diagnoses and treatment, we identified
      7174 cases of PE and 8923 cases of DVT. These cohorts were analyzed to provide
      incidence by age, race, sex, and geographic location; frequency of invasive
      treatment; frequency of PE after treatment for DVT; frequency of recurrence of
      PE; and survival after diagnosis. RESULTS: Annual incidence rates per 1000 at age
      65 to 69 years for PE and DVT were 1.3 and 1.8, respectively. Both rates
      increased steadily with age to 2.8 and 3.1 by age 85 to 89 years. For PE, women
      had lower rates than men (adjusted relative risk, 0.86; 95% confidence interval,
      0.82 to 0.90), and blacks had higher rates than whites (adjusted relative risk,
      1.25; 95% confidence interval, 1.15 to 1.36). For DVT, the associations with
      gender and race were weaker and in the opposite direction. Pulmonary embolectomy
      was done in 0.2% of cases of PE; interruption of the vena cava was done in 4.4%
      of cases of PE and in 2% of cases of DVT. Thrombectomy was done in 0.3% of all
      cases. Pulmonary embolism occurred in 1.7% of patients with DVT within 1 year of
      hospital discharge for initial treatment. The 1-year recurrence rate for PE was
      8.0%. In-hospital mortality associated with PE and DVT was 21% and 3%,
      respectively. One-year mortality was 39% and 21%, respectively. CONCLUSIONS:
      Pulmonary embolism and DVT are common problems in the elderly. Both increase with
      age, but the effects of race and sex are small. Current treatment patterns appear
      to be effective in preventing both PE after DVT and recurrence of PE. Both are
      associated with substantial 1-year mortality, suggesting the need to understand
      the role of associated conditions as well as the indications for prophylaxis and
      the methods of treatment.

PMID- 8154950
TI  - Improving empiric antibiotic selection using computer decision support.
AB  - BACKGROUND: Physicians frequently need to start antibiotic therapy before the
      results of bacterial cultures and antibiotic susceptibility tests are available.
      We developed and evaluated a computerized antibiotic consultant to assist
      physicians in the selection of appropriate empiric antibiotics. METHODS: We used
      a two-stage random-selection study to compare antibiotics suggested by the
      antibiotic consultant with 482 associated antibiotic susceptibility results and
      the concurrent antibiotics ordered by physicians. The antibiotics ordered by
      randomized physicians were then compared between crossover periods of antibiotic
      consultant use. RESULTS: The antibiotic consultant suggested an antibiotic
      regimen to which all isolated pathogens were shown to be susceptible for 453
      (94%) of 482 culture results, while physicians ordered an antibiotic regimen to
      which all isolated pathogens were susceptible for 369 culture results (77%) (P <
      .001). The physicians who prescribed antibiotics to which all pathogens were
      susceptible did so a mean of 21 hours after the culture specimens were collected.
      Physicians ordered appropriate antibiotics within 12 hours of the culture
      collection significantly more often when they had use of the antibiotic
      consultant than during the period before use (P < .035). Moreover, 88% of the
      physicians stated they would recommend the program to other physicians, 85% said
      the program improved their antibiotic selection, and 81% said they felt use of
      the program improved patient care. CONCLUSIONS: Information from computer-based
      medical records can be used to help improve physicians' selection of empiric
      antibiotics for infections.

PMID- 8154951
TI  - The contribution of non-insulin-dependent diabetes to lower-extremity amputation
      in the community.
AB  - BACKGROUND: Despite the significant public health burden of lower-extremity
      amputations in diabetes mellitus, few data are available on the epidemiology of
      lower-extremity amputations in diabetes mellitus in the community setting.
      METHODS: A retrospective incidence cohort study based in Rochester, Minn, was
      conducted. RESULTS: Among the 2015 diabetic individuals free of lower-extremity
      amputation at the diagnosis of diabetes mellitus, 57 individuals underwent 79
      lower-extremity amputations (incidence, 375 per 100,000 person-years; 95%
      confidence interval, 297 to 467). Among the 1826 patients with non-insulin
      dependent diabetes mellitus, 52 underwent 73 lower-extremity amputations, and the
      subsequent incidence of lower-extremity amputation among these residents was 388
      per 100,000 person-years (95% confidence interval, 304 to 487). Of the 137
      insulin-dependent diabetic patients, four subsequently underwent five lower
      extremity amputations (incidence, 283 per 100,000 person-years; 95% confidence
      interval, 92 to 659). Twenty-five years after the diagnosis of diabetes mellitus,
      the cumulative risk of one lower-extremity amputation was 11.2% in insulin
      dependent diabetes mellitus and 11.0% in non-insulin-dependent diabetes mellitus.
      When compared with lower-extremity amputation rates for Rochester residents
      without diabetes, patients with non-insulin-dependent diabetes mellitus were
      nearly 400 times more likely to undergo an initial transphalangeal amputation
      (rate ratio, 378.8) and had almost a 12-fold increased risk of a below-knee
      amputation (rate ratio, 11.8). In this community, more than 60% of lower
      extremity amputations were attributable to non-insulin-dependent diabetes
      mellitus. CONCLUSIONS: These population-based data document the magnitude of the
      elevated risk of lower-extremity amputation among diabetic individuals. Efforts
      should be made to identify more precisely risk factors for amputation in diabetes
      and to intervene in the processes leading to amputation.

PMID- 8154952
TI  - Enhanced auscultation with a new graphic display system.
AB  - BACKGROUND: To provide an objective method to support and teach auscultation, a
      new portable system (graphic display system) was evaluated for graphic display
      and printing of heart sounds. METHODS: Ninety-one patients from three
      institutions, with a variety of heart sound abnormalities, were studied by two
      examiners. A graphic recording was made in each and compared with the
      auscultatory findings. RESULTS: The findings of the graphic system confirmed the
      auscultatory impressions of both examiners in 77 (85%) of the 91 cases. Brief
      sound transients, such as split second sounds and ejection sounds, third heart
      sounds, and prosthetic opening and closing sounds, were all regularly recorded
      with the graphic system, often allowing resolution when examiners were in
      disagreement. Graphic recordings commonly were at variance with examiners in
      detecting fourth sounds, possibly because of examiners' difficulty in
      distinguishing these from split first sounds as well as limitations of the
      graphic system itself. High-pitched murmurs of low intensity (< grade 2), as
      exemplified by those of aortic and mitral regurgitation, were occasionally missed
      by the graphic system, probably because of baseline interference by background
      noise. CONCLUSIONS: The graphic display system can often provide more information
      than can be obtained by standard auscultation alone, especially in the detection
      of low-frequency and multiple sounds, and in the accurate timing of intervals. It
      is often unable to detect soft high-frequency murmurs. Permanent records allow
      for more objective comparison of the auscultatory findings of various examiners
      at different times. This system provides an excellent means by which auscultation
      skills may be taught or enhanced, especially since its speed and portability
      allow immediate feedback for comparison with auditory perceptions.

PMID- 8154953
TI  - The physician decision-making process in transferring nursing home patients to
      the hospital.
AB  - BACKGROUND: Each year more than 25% of nursing home patients are transferred to
      the emergency department or hospital for evaluation and treatment of infection.
      These transfers may have an adverse impact on the quality and cost of patient
      care. This study examined physician assessment and management of acute infections
      in the nursing home. METHODS: A cross-sectional study was conducted of all acute
      urinary tract infections and lower respiratory tract infections occurring from
      February through June 1991 in eight randomly selected urban nursing homes. The
      numbers of transfers to the emergency department of hospital were recorded along
      with identification of the clinical, psychosocial, and institutional factors that
      influenced the physician's decision to transfer. RESULTS: Three hundred fifty
      nine patients had 258 urinary tract infections and 219 respiratory tract
      infections. Eighty-one (17%) of these events resulted in transfer to a hospital
      for evaluation (16/81) and/or admission (65/81). Less than one third (30.4%) of
      the events caused the patient to be examined in the nursing home by a physician
      before the decision to transfer to the hospital. The mean time between the staff
      notification of an acute event and physician response by telephone was 5.12
      hours. Independent mobility (P < or = .05), a transfer to the hospital during the
      previous 6 months (P < or = .01), and fewer nursing home laboratory tests and
      treatments (P < or = .01) were all associated with hospital transfer.
      CONCLUSIONS: In this sample of acutely ill nursing home patients, physicians
      collected limited clinical data before the decision to transfer. Although some
      transfers may be appropriate, a reduction in the transfer rate may reduce health
      care costs and limit the risk of iatrogenesis, thus improving the outcome of
      acute illnesses occurring in the nursing home.

PMID- 8154954
TI  - Relationship of advance directives to physician-patient communication.
AB  - BACKGROUND: Although advance medical directives, such as living wills and durable
      powers of attorney for health care, are by themselves imperfect instruments for
      expressing patients' treatment preferences, a possible benefit of these documents
      is that they will enhance patient-physician communication, especially when end-of
      life treatment decisions have to be made. METHOD: Structured interviews were
      completed for 115 seriously ill cancer patients and 22 of their physicians. The
      questions dealt with various aspects of advance directives, including
      communications between the two parties regarding general and specific treatment
      wishes. Responses were compared in 37 physician-patient pairs for patients who
      had executed advance directives and in 31 physician-patient pairs for patients
      who had not executed advance directives. RESULTS: Physicians were frequently
      unaware of their patients' advance directives. Although patients with advance
      directives were marginally more likely than patients without advance directives
      to report discussions about end-of-life treatment decisions, only 34 (30%) out of
      the total of 115 patients claimed that they had any discussion of treatment
      decisions with their physicians. Such discussions tended to be about general life
      attitudes and feelings rather than specific treatments, such as use of artificial
      nutrition or ventilation. CONCLUSION: Despite public enthusiasm for the use of
      advance directives and great efforts to promote them, we found little evidence
      that these documents are associated with enhanced communication between patients
      and physicians about end-of-life treatment decisions.

PMID- 8154955
TI  - Antiphospholipid antibody syndrome mimicking multiple sclerosis clinically and by
      magnetic resonance imaging.

PMID- 8154956
TI  - Communicating magnesium content.

PMID- 8154957
TI  - Giant cell arteritis and Hitler.

PMID- 8154959
TI  - Papers presented at the 47th Annual Meeting of the New England Surgical Society.
      Cambridge, Massachusetts, October 29-31, 1993.

PMID- 8154958
TI  - Diogenes in the biliary tract.

PMID- 8154960
TI  - Pediatric surgery. Then and now.

PMID- 8154961
TI  - Second renal transplantations. Ethical issues clarified by outcome; outcome
      enhanced by a reliable crossmatch.
AB  - OBJECTIVE: To determine whether the appropriate use of scarce donor resources has
      been accomplished by renal retransplantation by reviewing the initial and long
      term outcomes of second-renal transplant recipients at the Massachusetts General
      Hospital, Boston. PATIENTS AND RESULTS: With a mean follow-up of nearly 5 years
      following transplantation, 54 (68%) of 80 second-transplant recipients had
      functioning allografts (allograft failure was defined by patient death or a
      return to dialysis). Rejection was the most common cause of failure (14 [54%] of
      26 patients). The 1-, 3-, and 5-year actuarial allograft survival rates were 86%,
      78%, and 69%, respectively, which were not significantly different from the
      survival rates of primary allografts at this center. These results support the
      continued approach of providing both cadaver-donor and living-donor renal
      allografts for recipients whose primary renal allograft has failed. The
      antiglobulin crossmatch may have contributed to the successful outcome by
      accurately determining compatibility and by averting early rejection failures.
      CONCLUSIONS: Health care policy reviewers should clearly distinguish the
      prospects for successful second renal transplants from the outcomes of extrarenal
      retransplantation. Moreover, because excellent second-renal allograft survival is
      attainable and comparable to primary-renal allograft survival and because the
      costs are comparable, restricting suitable patients to subsequent lifelong
      dialysis becomes unethical.

PMID- 8154962
TI  - A prospective comparison of laparoscopic and tension-free open herniorrhaphy.
AB  - OBJECTIVE: To compare results and outcomes following laparoscopic and tension
      free open inguinal herniorrhaphy. DESIGN: A prospective, nonrandomized trial of a
      single surgeon's experience. SETTING: A large university hospital. PATIENTS: The
      study included 100 patients with 116 hernias. Patients were offered open hernia
      repair or, if medically suitable for general anesthesia, a laparoscopic hernia
      repair. Fifty-seven patients underwent open repair and 43 patients underwent
      laparoscopic repair. INTERVENTION: Laparoscopic repair was performed using a
      transabdominal preperitoneal mesh technique. Open hernia repair was performed
      using a mesh-plug technique in which the hernia sac was reduced and held in place
      by a cone of mesh. The floor was covered with a second piece of mesh that
      encircled the cord and was sutured at the internal ring; it was held in place
      under the external oblique without sutures. RESULTS: Patients undergoing open
      repair were older than those undergoing laparoscopic repair. The distribution of
      hernia types was similar. The laparoscopic operation took longer than the open
      operation (mean [+/- SD], 1.9 +/- 0.4 hours vs 1.6 +/- 0.4 hours; P < .05), was
      more expensive ($4165 +/- $1154 vs $2985 +/- $1682; P < .05), and required more
      postoperative admissions (28% vs 3.5%). There were three recurrences in the
      laparoscopic group and none in the open group. Patients undergoing laparoscopic
      repair consumed the same amount of narcotic analgesics as did the group
      undergoing open repair and had discomfort for the same amount of time. Patients
      undergoing laparoscopic repair returned to work sooner than did patients
      undergoing open repair (5.6 days vs 10.3 days; P < .05). CONCLUSIONS:
      Laparoscopic hernia repair returns patients to the workplace faster than open
      hernia repair despite a similar analgesic requirement. The laparoscopic repair
      costs more and has a higher recurrence rate than open repair. Laparoscopic repair
      is most suitable for bilateral hernias. Further investigation of this technique
      is required before its wide-scale application can be recommended.

PMID- 8154964
TI  - Failure of symptomatic relief after pancreaticojejunal decompression for chronic
      pancreatitis. Strategies for salvage.
AB  - OBJECTIVE: To evaluate causes of intractable recurrent pain following
      pancreaticojejunostomy for chronic pancreatitis and to evaluate treatment
      strategies aimed at lasting pain relief. DESIGN: Case series. SETTING: Tertiary
      care referral center. PATIENTS: Fifteen selected patients having severe pain
      associated with chronic pancreatitis with onset 0 to 60 months (median, 5 months)
      following pancreaticojejunostomy. Each patient underwent computed tomography and
      endoscopic retrograde cholangiopancreatography. Two patients (13%) were found to
      have pancreatic cancer, two (13%) had inadequate pancreatic duct decompression,
      two (13%) had biliary stenosis, and 10 (67%) had presumed neuropathy in the
      pancreatic head. INTERVENTIONS: Fourteen (93%) of the 15 patients underwent the
      following reoperations: distal pancreatectomy and splenectomy (one patient),
      extension of the pancreaticojejunostomy and choledochojejunostomy (one patient),
      biliary stenting followed by choledochojejunostomy (one patient), and Whipple
      type resection of the pancreatic head (14 patients). Two patients subsequently
      underwent a completion pancreatectomy. MAIN OUTCOME MEASURES: Pain relief,
      functional capacity, and pancreatic exocrine and endocrine status were
      determined. The median follow-up after reoperation was 39 months. RESULTS: Of the
      14 patients who underwent reoperation, 13 were long-term survivors. One died of
      pancreatic cancer. Ten of the other 13 have had satisfactory-to-excellent relief
      of pain, with resumption of a normal level of function. Of the 10 previously
      euglycemic patients who underwent pancreatic head resection, eight remain free of
      diabetes mellitus to date. CONCLUSIONS: The causes of recurrent or persistent
      pain following pancreaticojejunal decompression for chronic pancreatitis are
      complex and include neuropathic changes, residual or evolving pancreatic and
      biliary duct obstruction, and unrecognized pancreatic cancer. Acceptable outcomes
      can usually be achieved by following a treatment strategy aimed at addressing
      identified residual disease while maximally preserving pancreatic tissue.

PMID- 8154963
TI  - K-ras-2 topographic genotyping of pancreatic adenocarcinoma.
AB  - OBJECTIVE: To determine the frequency distribution of K-ras-2 point mutation
      genotypes in pancreatic adenocarcinoma and to evaluate the effectiveness of K-ras
      2 genotyping as a means to predict localized disease and potential long-term
      survival. DESIGN: Topographic genotyping from archival formalin-fixed, paraffin
      embedded large- and biopsy-sized tissue specimens as well as cytologic fluid
      using polymerase chain reaction products and direct sequencing together with
      clinicopathologic and statistical analysis. SETTING: Tertiary care medical center
      with molecular diagnostics pathology laboratory. PATIENTS: Patients treated
      between 1988 and 1993 at Rhode Island Hospital, Providence, yielding 55 primary
      and 56 metastatic specimens of pancreatic adenocarcinoma. RESULTS: Each primary
      pancreatic adenocarcinoma was found to contain one of eight specific genotypes
      that was maintained in all metastatic deposits of that individual tumor. Primary
      adenocarcinomas confined to the pancreatic bed at diagnosis were predominantly of
      a normal genotype (56% [14/25]). Pancreatic adenocarcinomas progressing to
      distant hematogenous metastasis were almost exclusively mutated (88% [7/8]; P <
      .005). Patients undergoing pancreatic resection (Whipple's operation) and having
      a normal K-ras-2-genotype (58% [11/19]) had a significantly longer survival (21.3
      months) than similar patients with mutated tumors (8.2 months). CONCLUSIONS: The
      findings support the feasibility of K-ras-2 topographic genotyping to identify
      potentially indolent disease and suggest a potentially useful role in the
      preoperative evaluation of pancreatic adenocarcinoma.

PMID- 8154965
TI  - Total pelvic exenteration. A 50-year experience at the Ellis Fischel Cancer
      Center.
AB  - OBJECTIVE: To review a 50-year experience with total pelvic exenteration for
      treatment of advanced pelvic cancer. DESIGN: Retrospective study with 100% follow
      up. SETTING: Cancer hospital. PATIENTS: Two hundred thirty-two patients referred
      for treatment of advanced pelvic cancer who underwent total pelvic exenteration.
      MAIN OUTCOME MEASURES: Rates of operative mortality, complications, recurrence,
      and 5-year survival. RESULTS: The morbidity rate was 45%. The operative death
      rate was 14% during the 50-year period, but decreased from 16.8% in the first
      three decades to 10% thereafter. Eighty-nine patients (38%) had recurrences. The
      overall 5-year survival rate was 42%. CONCLUSIONS: Operative mortality and
      morbidity have declined over 50 years, largely because of proper patient
      selection, increasing experience, and advances in perioperative care.
      Exenteration has a major role in the treatment of advanced pelvic cancer.

PMID- 8154966
TI  - Medicolegal analysis of the delayed diagnosis of cancer in 338 cases in the
      United States.
AB  - OBJECTIVE: To define the frequency, clinical characteristics, and legal outcomes
      of the delayed diagnosis of cancer leading to negligence litigation. DESIGN:
      Retrospective review of 338 jury verdict reports from 42 states in the United
      States. SETTING: State and federal civil court decisions, as reported to
      litigation survey services, in a 5-year interval from 1985 to 1990. RESULTS: Of
      338 cancers divided into 13 major organ sites, breast (38%, n = 127),
      gastrointestinal (15%, n = 51), lung (15%, n = 50), and head and neck cancers
      (10%, n = 33) accounted for 80% (270/338) of lawsuits. The average diagnostic
      delay for 212 cases was 17 months. The median age of patients with delays was 15
      years younger than the age of patients presenting with cancer in the general
      population. For cancers in nine major organ sites, the ratio of mortality for
      patients filing lawsuits to that for patients with cancer in the general
      population averaged 3.4:1. The total known indemnity payout was $140.2 million,
      with an average payout per case of $64,600. At 1 to 3 months of diagnostic delay,
      jury verdicts largely favored the defense (seven of 11 [65%] defense verdicts);
      after 6 months of delay, jury verdicts were almost evenly divided between defense
      verdicts, plaintiff verdicts, and out-of-court settlements. CONCLUSIONS: The
      delayed diagnosis of cancer leading to negligence litigation is associated with
      significant indemnity payments, often involves middle-aged patients far younger
      than the expected age in the general cancer population, and is defensible only in
      the minority after 6 months of diagnostic delay.

PMID- 8154967
TI  - Parastomal hernia. Is stoma relocation superior to fascial repair?
AB  - OBJECTIVE: To evaluate methods of parastomal hernia repair. DESIGN: Retrospective
      analysis. SETTING: Two tertiary care institutions. PATIENTS: Eighty patients
      undergoing 94 parastomal hernia repairs between 1983 and 1991. INTERVENTIONS:
      Three methods of repair were examined: fascial repair, stoma relocation, and
      fascial repair with prosthetic material. MAIN OUTCOME MEASURE: Parastomal hernia
      recurrence and short- and long-term complications. RESULTS: Fifty-five (93%) of
      59 living patients were available and examined at a median of 31.5 months
      following repair, providing 68 repairs for consideration. Fascial repair was used
      in 36 cases, stoma relocation in 25 cases, and fascial repair with prosthetic
      material in seven cases. Overall, 63% of patients developed a recurrent
      parastomal hernia and 63% had at least one postoperative complication. Following
      first-time repair, parastomal hernia recurrence developed in 22 (76%) of 29
      patients who had fascial repair but in only six (33%) of 18 patients who had
      stoma relocation (P < .01). When repair was undertaken for recurrent parastomal
      hernia, fascial repair failed in all seven cases, stoma relocation failed in five
      (71%) of seven cases, and fascial repair with prosthetic material failed in one
      (33%) of three cases. The only factor that significantly affected the recurrence
      rate was the technique of repair. Complications were more common following stoma
      relocation (88%) than following fascial repair (50%) (P < .05). In particular,
      incisional hernias developed in 52% of patients following stoma relocation but in
      only 3% of patients following fascial repair. When postoperative occurrence of
      all abdominal-wall hernias was compared, there was no significant difference
      between the fascial repair group (29 [81%] of 36 repairs) and the stoma
      relocation group (17 [68%] of 25 repairs). Furthermore, the reoperation rate for
      hernia repair was nearly identical (31% vs 28%) between these two groups.
      CONCLUSIONS: Parastomal hernia repair is often unsuccessful and rarely without
      complication. For first-time parastomal hernia repairs, stoma relocation is
      superior to fascial repair. For recurrent parastomal hernias, repair with
      prosthetic material is the most promising of a group of poor alternatives.

PMID- 8154968
TI  - Gastric pull-up reconstruction for pharyngo-laryngo-esophagectomy.
AB  - OBJECTIVE: To determine the results of gastric pull-up reconstruction following
      pharyngo-laryngo-esophagectomy. DESIGN: Retrospective review of 59 patients who
      underwent gastric pull-up reconstruction for carcinoma of the hypopharynx,
      larynx, and cervical esophagus during a 10-year period from 1983 to 1993.
      SETTING: Combined Head and Neck Service and Section of General Surgery,
      Department of Surgery, Yale University Medical School, New Haven, Conn. MAIN
      OUTCOME MEASURES: Morbidity, mortality, time to oral feeding, length of
      hospitalization, and long-term results. RESULTS: The mortality rate was 5%,
      perioperative morbidity rate, 27%, and the medical morbidity rate, 32%. Most
      patients took oral feedings within 6 days after surgery and were discharged
      within 16 days. There were two temporary fistulas and four strictures, none of
      which were permanent. There were no intrathoracic or mediastinal injuries or
      hemorrhage. The overall survival was 1 to 100 months (median survival, 12
      months); the median survival was 34 months for patients alive to date and 8
      months for patients who died. CONCLUSIONS: The gastric pull-up reconstruction is
      a safe, effective operation with a low mortality rate and excellent long-term
      functional results for patients with extensive carcinoma of the hypopharynx,
      larynx, and cervical esophagus.

PMID- 8154969
TI  - Intraoperative ultrasound imaging of the liver at the time of colorectal cancer
      resection.
AB  - OBJECTIVES: To evaluate the accuracy of intraoperative ultrasound (IOUS) liver
      imaging at the time of primary colorectal cancer resection, which might eliminate
      incurable patients from adjuvant chemotherapy trials or permit earlier resection
      of curable metastases. DESIGN: A prospective trial of routine IOUS liver imaging
      during resections of primary colorectal cancer. The rate of detection of occult
      metastases by IOUS imaging alone and the false-negative rate over 22.7 months of
      follow-up were determined. SETTING: A tertiary care referral center in Boston,
      Mass. PATIENTS: Fifty-five patients undergoing 56 operations for colorectal
      carcinoma between May 1990 and June 1992. MAIN OUTCOME MEASURES: The rate of
      detection, by IOUS imaging alone, of otherwise occult hepatic metastases, the
      total number of patients with metastases detected at any time during follow-up,
      and the rate of false-negative findings on IOUS imaging and direct examination.
      RESULTS: Occult hepatic metastases were detected by IOUS imaging alone in 5% of
      patients. Restriction of IOUS imaging to patients with T3 or T4 lesions or
      recurrent cancers would have identified all metastases and increased the
      detection rate to 10%. Occult metastases were detected by IOUS imaging alone in
      12.5% of patients with T3, N0 lesions. The rate of false-negative findings on
      IOUS imaging was 13% overall, 0% for patients with T1 or T2 lesions, 3% for
      patients with node-negative findings, and 7% for patients with T3, N0 lesions.
      CONCLUSIONS: The small increment in the detection of occult metastases by IOUS
      liver imaging does not warrant its use in all patients with colorectal cancer.
      Selective use in patients with T3 or T4 lesions or recurrent cancers increased
      the incremental gain in detection. The observed frequency of occult metastases in
      patients with T3, N0 lesions is sufficient to impact on results of adjuvant
      chemotherapy trials. Longer follow-up in more patients is needed to determine
      whether a negative IOUS study is an additional favorable prognosticator in
      patients with T1 and T2 lesions and node-negative findings.

PMID- 8154970
TI  - Detection of postoperative sepsis in infants with the use of metabolic stress
      monitoring.
AB  - OBJECTIVES: To evaluate the ability of serial protein metabolic monitoring to
      detect postoperative injury due to serious bacterial infection in infants by
      comparing changes observed in these protein parameters with more conventionally
      accepted indexes of infection. DESIGN: Retrospective review of infants whose
      postoperative course was complicated by bacterial infection compared with a
      matched cohort of infants in whom bacterial infection did not develop
      postoperatively. SETTING: Neonatal and pediatric intensive care units at the Wake
      Forest University Medical Center, Winston-Salem, NC. PATIENTS: Critically ill
      infants (N = 40) recovering from major surgical intervention. MAIN OUTCOME
      MEASURES: Serum C-reactive protein, prealbumin, and tumor necrosis factor
      concentrations were compared with the white blood cell count, immature-total
      neutrophil ratio, and body temperature obtained within 24 hours before and
      following the new onset of culture-established postoperative bacterial infection
      in 13 infants. These infants were compared with a matched cohort of 27 infants in
      whom postoperative bacterial infection did not develop. RESULTS: Only C-reactive
      protein (P = .0001) and prealbumin (P = .0003) levels were significantly altered
      in association with the onset of serious bacterial infection (paired t test). The
      C-reactive protein levels were clearly superior to all other variables in
      predicting postoperative infection (at cutoff point > 6.0 mg/dL; sensitivity,
      92%; specificity, 96%). The predictive power of prealbumin level was lower, but
      acceptable (at cutoff point < or = 9.0 mg/dL; sensitivity, 85%; specificity,
      74%). CONCLUSIONS: Monitoring of serial protein metabolic stress with C-reactive
      protein and prealbumin levels in infants following operations is more effective
      than the white blood cell count, immature-total neutrophil ratio, or temperature
      in detecting serious postoperative infections.

PMID- 8154971
TI  - Prophylaxis of primary cytomegalovirus disease in renal transplant recipients. A
      trial of ganciclovir vs immunoglobulin.
AB  - OBJECTIVE: To compare the efficacy, safety, and cost of prophylactic low-dose
      ganciclovir with that of immunoglobulin in renal transplant recipients at risk
      for primary cytomegalovirus (CMV) disease. DESIGN AND SETTING: A prospective,
      randomized trial at a 650-bed tertiary medical center hospital. PATIENTS: Fifty
      one consecutive CMV-seronegative patients who received renal allografts from
      seropositive donors between March 1990 and April 1992. MAIN OUTCOME MEASURES:
      Patient and allograft survival, and the incidence and severity of CMV disease.
      INTERVENTION: Cytomegalovirus prophylaxis with seven doses of intravenous
      immunoglobulin for 6-week periods (group 1, n = 27) or low-dose intravenous
      ganciclovir for 3 weeks (group 2, n = 24). Results were compared with those
      obtained in 23 CMV-seronegative historical controls who received renal allografts
      from CMV-seropositive donors between 1987 and 1989, and who did not receive
      prophylaxis for CMV (group 3). RESULTS: Both prophylactic regimens significantly
      reduced the incidence of invasive CMV infection (P < .05) and were well
      tolerated. However, the cost of ganciclovir ($350 per patient) was substantially
      less than that of immunoglobulin ($4000 per patient). CONCLUSIONS: These data
      suggest that prophylactic ganciclovir therapy provides a cost-effective approach
      toward significantly improving the outcome of renal transplantation in recipients
      at risk for primary CMV disease.

PMID- 8154972
TI  - Mortality factors in geriatric blunt trauma patients.
AB  - OBJECTIVE: To examine various clinical factors for their ability to predict
      mortality in geriatric patients following blunt trauma. DESIGN: In this
      retrospective study, trauma registries and medical records from three trauma
      centers were reviewed for patients 65 years and older who had sustained blunt
      trauma. The following variables were extracted and examined independently and in
      combination for their ability to predict death: age, gender, mechanism of injury,
      admission blood pressure, and Glasgow Coma Scale score, respiratory status,
      Trauma Score, Revised Trauma Score, and Injury Severity Score. SETTING: Three
      urban trauma centers. PATIENTS: Geriatric trauma patients entering three trauma
      centers (Stanford [Calif] University Hospital, Vanderbilt University Medical
      Center, Nashville, Tenn, and Maryland Institute for Emergency Medical Services
      Systems, Baltimore) following blunt trauma during a 7-year period (1982 to 1989).
      RESULTS: The Injury Severity Score was the single variable that correlated most
      significantly with mortality. Mortality rates were higher for men than for women
      and were significantly higher in patients 75 years and older. Admission variables
      associated with the highest relative risks of death included a Trauma Score less
      than 7; hypotension (systolic blood pressure, < 90 mm Hg); hypoventilation
      (respiratory rate, < 10 breaths per minute); or a Glasgow Coma Scale score equal
      to 3. CONCLUSIONS: Admission variables in geriatric trauma patients can be used
      to predict outcome and may also be useful in making decisions about triage,
      quality assurance, and use of intensive care unit beds.

PMID- 8154973
TI  - The first carotid endarterectomy at the Johns Hopkins Hospital.

PMID- 8154975
TI  - Surgery in Japan.

PMID- 8154974
TI  - Occult hypoadrenalism in critically ill patients.

PMID- 8154976
TI  - [Morphology of recent meningococcal infections in children].
AB  - An analysis of 108 cases of children's death which occurred in 1981-1991 from
      hypertoxic meningococcal infection (MI) in St. Petersburg is presented. Serogroup
      B meningococcus as a causative agent was found in 44% of the cases. The role in
      the thanatogenesis of inflammatory and immune reactions, viral-bacterial
      associations was shown on the basis of detailed study of 47 cases. Hemorrhagic
      adrenal necrosis was diagnosed in 94.7% of the cases. Two clinicomorphological
      variants of the disease are distinguished: 1) variant with a moderate hemorrhagic
      eruption without pronounced kidney lesion, 2) variant with an abundant confluent
      rash and pronounced kidney lesions and choroid plexus immune lesions.

PMID- 8154977
TI  - [Morphologic aspects of hemostasis disturbances in meningococcemia in children].
AB  - 21 children who died from meningococcemia were studied. Shock disturbances of the
      microcirculation and thrombocytic part of hemostasis prevailed within first hours
      of the disease in the form of adrenal hemorrhages and brain edema as immediate
      cause of death. With an increase of the disease duration, aggregational
      thrombocytopenia, generalized microthrombosis, coagulopathy, fibrinolysis
      activation resulted in massive hemorrhages in a number of organs and tissues and
      manifested in the syndrome of polyorganic failure. No significant differences
      were found depending upon treatment.

PMID- 8154978
TI  - [Experimental model of generalized herpetic infection in newborns].
AB  - Generalized herpetic infection (GI) with a predominant involvement of the brain,
      eye, liver and spleen, in which cell rhexis and hyperchromatosis and large
      necrotic foci were observed, has been experimentally reproduced in newborn
      rabbits. Administration of herpes simplex virus at the dose of 5LD50 resulted in
      the suppression of immune reactions and animal death 4-5 days later. Dose of
      2LD50 resulted in the immune response in the lymphoid organs, but the signs of
      the disease disappeared 5 days after the injection of the virus. The hypothesis
      on the existence of several clinico-morphological variants of GI is postulated.

PMID- 8154979
TI  - [Basic unresolved problems of perinatal and pediatric pathology].
AB  - The autopsy of all spontaneous abortions, but not only of dead children is
      considered to be desirable to determine their diseases among which infections are
      frequent. The study of miscarriages lacking severe chronic pathology is important
      for obtaining reliable anthropometric data. The necessity of a rapid (within 1-2
      days) examination of all placentas for determination of risk groups among mothers
      and children of purulent septic diseases as well as the causes of premature
      deliveries, asphyxia development and other disorders is discussed. Infections
      placentitis is frequently found when the placentas are carefully studied. The
      attention should be paid to frequently observed combined infections. Serious
      problem is careful investigation of syndromes (sudden infant death, infantile
      cerebral paralysis and others).

PMID- 8154980
TI  - [Infectious toxic shock in generalized rotaviral infection in newborns].
AB  - The possibility of the rotavirus infection generalization, the course of which
      was complicated by the infectious toxic shock and disseminated intravascular
      coagulation syndrome as a cause of death of three newborns is shown for the first
      time. Etiology of the disease was established by electron microscopy,
      immunoenzymatic and immunofluorescent methods in the faeces, blood and postmortem
      material. The manifestations of giant cell metamorphosis not only in the
      intestine but also in the pia mater, kidneys, liver, lungs characteristic of RNA
      viral infections indirectly confirmed the presence of viremia. Combination of
      rota- and respiratory syncytial viral infections made a pathologic process more
      severe with the development of necrotising enterocolitis, perforative serous
      peritonitis, intraabdominal hemorrhage.

PMID- 8154981
TI  - [Morphologic manifestations of "prune belly" syndrome as shown by autopsy and
      surgical speciments].
AB  - The organs were morphologically studied in 21 children at the age of 4 days to 12
      who died of or were operated for "prune belly" syndrome. Muscle hypoplasia and
      muscle aplasia in 2 cases in the anterior abdominal wall were found. Dysplastic
      processes with chronic pyelonephritis and ureteritis were observed in the kidneys
      and ureters. The relation of kidney and ureter dysplasia with intrauterine
      cytomegaly was suspected in 4 cases.

PMID- 8154982
TI  - [Pathomorphologic structural variants of fetal membranes in oligohydroamnios].
AB  - Morphological heterogeneity of oligohydroamnion in 25 cases is shown.
      Inflammatory processes of hematogenic origin prevailed in 36% of cases; in 40%
      there were atrophic processes or microcystic transformation of the decidual
      endometrial glands against the background of the endometrial deficiency;
      dysontogenetic forms with the preservation of a large number of atrophic villi in
      the cytotrophoblast were observed in 24% cases. These variants should be taken
      into consideration when a differential treatment is developed.

PMID- 8154983
TI  - [Possibilities and limitations in the morphologic study of the thyroid gland].
AB  - The comparative evaluation of thyroid pathology in different regions should
      include biopsy and autopsy examination. Morphological research (cytological and
      histological methods) implies 3 steps: preoperative, intraoperative and
      postoperative. The results of cytological and histological examination should be
      properly used by clinicians. For successful comparative ecological research it is
      necessary to use reliable methods of investigation of thyroid goiter and thyroid
      tumours. These methods provide evaluation of real morphofunctional state of
      thyroid pathology in different regions.

PMID- 8154984
TI  - [Morphology of granulomatous inflammation in pseudotuberculosis].
AB  - The study of pathology in pseudotuberculosis has showed that clinical and
      morphological nature of the disease is related to granulomatous inflammation in
      organs and tissues. The authors have established that a relapsing course of this
      infection may be due to pronounced specific sensitization of the body when
      granulomas appear in large numbers. Morphogenesis of acute granulomatous
      inflammation in pseudotuberculosis reflects a consecutive involvement of cellular
      reactions of the immediate and delayed hypersensitivity. In the authors' opinion
      pseudotuberculosis granulomas may be assigned to immune hypersensitive granulomas
      of mixed type according to the classification suggested by A. I. Strukov and O.
      Ya. Kaufman. The data obtained allow a hypothesis that granulomas tending to
      cause a purulent liquefaction and necrosis, like pseudo-tuberculous granulomas,
      could be considered as a morphological sign of granulocytic-macrophagal immune
      deficiency.

PMID- 8154985
TI  - [Morphofunctional characteristics of malignant thyroid gland tumors in children
      from various regions of the Ukraine, who have been victims of of the Chernobyl
      nuclear power plant accident].
AB  - Thyroid cancers in children from the affected areas of Ukraine were investigated
      by means of light (33 cases) and electron (20 cases) microscopy. Statistical data
      from 25 regions of Ukraine have been analyzed concerning thyroid cancer in
      patients aged up to 18 years for the period 1981-1990. There is an increase in
      the number of thyroid cancers in the children of Ukraine from 0.04-0.06 cases in
      the "pre-chernobyl" period to 0.23 cases per 10(5) children's population in 1990.
      In the children operated in the Clinic of the Institute of Endocrinology in 1990
      1991, severe forms of thyroid lesions with metastases to the lymph nodes were
      noted. Histopathological studies show prevalence of different variants of
      papillary cancer with presence of follicular, solid, poorly differentiated areas.
      Ultrastructural analysis revealed polymorphism of tumour cells, various degrees
      of their differentiation and functional specialization that point to a mixed
      multicomponent nature of carcinomas.

PMID- 8154986
TI  - [Cytomorphology of papillary carcinoma of the thyroid gland in children].
AB  - Of 632 thyroid fine-needle aspirations (FNA) performed by the authors throughout
      1990-1992, 24 cases were cytologically diagnosed as neoplastic. Cases under study
      were papillary carcinomas in 5-16 year olds; 21 correctly diagnosed at FNA, two
      false negative and one suspected. Three-dimensional tissue fragments, follicular
      cells with dense cytoplasm, well defined cell margins, eccentric large clear
      nuclei, dusty chromatin were among the most consistent features observed. High
      cellularity, papillary clusters, intranuclear cytoplasmic inclusions, were found
      in half (54.17%) of the cases only.

PMID- 8154987
TI  - [Value of rapid biopsy in diagnosis of thyroid cancer].
AB  - Patients with thyroid carcinoma (ThC) in 67% are erroneously operated on with the
      diagnosis of nodular struma, this resulting in the recurrences in 30% and
      mortality and complications reaching 42%. Since 1977 the authors were performing
      rapid biopsies in all cases of the euthyroid struma and this resulted in the
      proper diagnosis in 98% of operated patients (48.6% before this). Short-term
      examination consists of stereo-morphology of the surgical material and the
      preparation by means of the deep frozen knife, of the histo-topographical section
      stained by Harris hematoxylin. Microcarcinomas are revealed by this method 30
      times more frequently than in routinely treated sections. Short-term biopsy of
      the thyroid is as necessary as it is in the mammary gland lesions.

PMID- 8154988
TI  - [Lightwood-Albright's syndrome in a newborn].
AB  - One observation of the rare syndrome is described in a 5-year-old child. The
      cause of death was asphyxia due to the mothers milk aspiration.

PMID- 8154989
TI  - [A rare tumor of the knee joint].
AB  - The tumour in a male of 62 consisted of vesicular vacuolized cells in a
      myxomatous substance. References are given as to the morphological similarity
      between chondrosarcoma and so-called chordoid-sarcoma. At the light and electron
      microscopic level the signs of incomplete chondrogenesis are found, this
      permitting one to consider the tumour as a myxoid variant of chondrosarcoma.

PMID- 8154990
TI  - [Levels of immunoglobulins E in postmortem blood serum as a diagnostic criterium
      of death from anaphylactic shock].
AB  - In patient who died from anaphylactic shock the level of immunoglobulins E in
      postmortem blood exceeded the upper limit almost 6 times this allowing to confirm
      the diagnosis. It is stated that a postmortem blood examination may be useful in
      the autopsy diagnosis of anaphylactic shock.

PMID- 8154991
TI  - [Detection of hepatitis B virus DNA using local nucleic acid amplification
      (polymerase chain reaction) in fixed tissues in chronic viral liver diseases].
AB  - PCR is a highly sensitive, convenient and rapid method for detection of viral DNA
      in fixed tissue samples which allows one to analyse the material from the
      pathology files, mainly biopsies. PCR in a fixed material requires larger amounts
      of DNA-polymerase and longer duration of every stage of thermo-cycles compared to
      PCR in the purified DNA samples.

PMID- 8154992
TI  - [The "golden" decade of the Odessa autopsy room. (120th anniversary of the
      autopsy room at Odessa Municipal Hospital)].

PMID- 8154993
TI  - [Status and perspectives of development of a pediatric pathology service in Saint
      Petersburg and the Leningrad region].
AB  - The structure, development and perspectives of the pathology service in St.
      Petersburg and Leningrad Region are described. Preliminary data on the proportion
      of various diseases in children dying during perinatal period and miscarriages
      are presented, high incidence of intrauterine infections is indicated.

PMID- 8154994
TI  - [Infectious placentitis and characterization of the placenta as an immune
      barrier].
AB  - Analysis of publications dealing with infectious pathology of placenta is
      performed. Placentitis of different etiology and different routes of
      contamination have specific features. The incidence of viral and mycoplasma
      etiology with intracellular multiplication of the agent is considerably higher
      than of bacterial or other placentitis with extracellular multiplication. The
      incidence of placentitis is considerably higher than that of intrauterine
      infection. Placenta is an organ of immune protection of the organism and is
      capable to produce both specific and non-specific immunity factors.

PMID- 8154996
TI  - [Etiological treatment of Chagas disease. Consensus and divergence].

PMID- 8154995
TI  - [Tissue of ultimobranchial origin in normal and pathologically altered thyroid
      gland].
AB  - Heterogeneity of the thyroid parenchyma and the sources of development of its
      main components are considered. The least studied are components originating from
      the ultimobranchial body to which "the second" system of the ultimobranchial
      follicles and solid epithelial cell nests belong. The data on the incidence,
      topography and age dynamics of these nests are presented. Their histochemical and
      immunocytochemical characteristics are given. Hypothesis on a possible role of
      solid cell nests as a source of various cell types in the thyroid as well as on
      their probable participation in the genesis of mixed thyroid tumours is
      discussed.

PMID- 8154997
TI  - [Trypanosoma cruzi and chronic Chagas heart disease].

PMID- 8154998
TI  - [Scintigraphy of myocardial perfusion combined with pharmacologic stress with
      dipyridamole].
AB  - PURPOSE: To analyze adverse reactions (AR), hemodynamic and electrocardiographic
      changes and thallium scintigraphy (TS) results, during pharmacological stress
      with dipyridamole (SD), correlating these data to the presence and extension of
      coronary artery disease (CAD). METHODS: We studied 126 patients, 66 had no
      evidence of cardiovascular disease (G1) and 60 had critical occlusive CAD > or =
      70% stenosis (G2). Most of them were male, mean age 56.5 +/- 10.9 years old. All
      patients were submitted to TS after receiving 0.56 mg/kg of dipyridamole
      intravenously (0.14 mg/min during 4 min) followed by 111MBq of thallium-chloride
      201. Conventional ECG was recorded before and after SD; heart rate (HR) and
      arterial pressure (AP) were monitored during dipyridamole infusion. All signals
      and/or symptoms were observed. RESULTS: Cine-coronarography showed 22 patients
      (37%) with one vessel disease (VD) (G2a), 26 (46%) with two VD (G2b) and 12 (20%)
      with three VD (G2c). Of the 126 patients 63% did not present symptoms. Flushing
      (25%) and sick-headache (12%) were most frequent AR. Typical angina was reported
      by one G1 patient (1.5%) and six G2 patients (10%) (p < 0.05). HR increased 18.09
      +/- 12.27% and 12.40 +/- 4.90%, systolic blood pressure varied -5.2 +/- 7.5% and 
      4.3 +/- 6.5% in G1 and G2, respectively. These parameters are not correlated to
      CAD presence and extension. ST depression and ectopic beats occurred in 5% and
      11% of G1 patients, in 15% and 30% of G2 patients, respectively (p < 0.05).
      Typical angina was more common in G2a and G2b; ST changes in G2b and G2c; and
      arrhythmia in G2c (not significant). Sensitivity of TS associated to SD was 84%,
      comparable to stress exercise thallium test. CONCLUSION: TS associated to SD, a
      noninvasive, safe with low morbidity and few collateral effects method is an
      option to patients with limitations to physical exercise tests.

PMID- 8154999
TI  - [Mitral valvuloplasty with Inoue balloon catheter. Analysis of 112 cases].
AB  - PURPOSE: To present immediate results of percutaneous mitral valvuloplasty (PVM)
      with Inoue balloon for the treatment of mitral stenosis. METHODS: One hundred and
      twelve consecutive patients mean age 31.26 +/- 9.5 years, 82% females, the
      majority in functional class III/IV (69%) underwent percutaneous mitral
      valvuloplasty (PVM) with Inoue balloon. The procedure was undertaken by the
      transseptal technique. RESULTS: PMV achieved significant reduction in mean left
      atrial pressure pre 24.57 +/- 5.37 post 12.36 +/- 4.82, mitral gradient pre 15.31
      +/- 4.28 post 3.48 +/- 2.09 and increased mitral valve area pre 0.88 +/- 0.12
      post 2.0 +/- 0.28 (P < 0.001). An increase of at least 25% of the mitral valve
      area with a final result greater than 1.5 cm2 was obtained in 96% of the cases.
      Cardiac tamponade occurred in five cases (4.4%). In 4 a successful treatment was
      accomplished in the catheterization laboratory. Significant mitral regurgitation
      was seen in one case (0.9%) and there was one death (0.9%). CONCLUSION: The
      results of this series attest to the effectiveness of the PMV with Inoue balloon
      in selected cases of mitral stenosis.

PMID- 8155000
TI  - [Relationship between volume reduction of the left ventricle and the increase of
      mitral valve prolapse. An experimental study in dogs].
AB  - PURPOSE: To verify whether accentuated reductions of left ventricular volume lead
      to mitral valve prolapse. METHODS: Seven mongrel dogs were bled through the
      internal jugular vein, the systolic systemic pressure being kept between 100 and
      140 mmHg by means of continuous infusion of dopamine; the inferior vena cava
      vein, in tree other dogs, was partially obstructed for 4 to 6 seconds; epicardial
      echocardiography was carried out in all cases. RESULTS: Reductions of volemia
      were about 50% of the estimated total blood volume. Systolic internal diameter of
      left ventricle decreased about 25% and systolic ostial diameter, about 12.5%.
      Three out of seven died suddenly from arrhythmia before one has reached a
      significant decrease in total blood volume; one showed momentary mitral valve
      prolapse, during a period of hypotension; however, this prolapse disappeared
      completely when systemic blood pressure was restored by increasing the dopamine
      dosage; one dog had slight systolic displacement of the anterior cusp toward left
      atrium (0.5mm) and the last two showed no change; one out of 3 dogs submitted to
      partial constriction of inferior vena cava had systolic displacement of anterior
      cusp of 1mm; in one case there was an equivalent degree of displacement of the
      anterior cusp toward the left ventricle and in the last one no change was
      detected. In all dogs there was a change in the dynamics of mitral valve closure:
      with accentuated reduction of left ventricular volume the posterior cusp became
      less mobile, the anterior cusp being the principal responsible for the systolic
      ostial occlusion. CONCLUSION: Accentuated reduction of dog's left ventricular
      volume does not, necessarily, cause mitral valve prolapse but only slight
      displacement of the anterior cusp toward the left atrium in some animals or no
      displacement at all.

PMID- 8155001
TI  - [Correlation between ventricular arrhythmia and geometric remodeling of the left
      ventricle in arterial hypertension].
AB  - PURPOSE: To study the presence and type of ventricular arrhythmias in patients
      with different geometric patterns of the left ventricle (LV). METHODS: Seventy
      two patients with essential hypertension were divided in 4 groups, by the
      echocardiographic patterns: group I with concentric remodeling of the LV (normal
      LV mass with increased relative wall thickening); group II with concentric
      hypertrophy (both LV mass and relative wall thickening increased); group III with
      normal geometry of the LV (both LV mass and relative wall thickening normal);
      group IV, with eccentric hypertrophy (increased LV mass with normal relative wall
      thickening). The groups were compared by the quantity and quality of ventricular
      arrhythmia, measured by the number of ventricular ectopic beats (VEB) and
      episodes of ventricular tachycardia (VT) on Holter monitoring, and the presence
      of late potentials (LP) on signal-averaged electrocardiogram. RESULTS: Group I
      showed fewer VEB than group II (16.2 +/- 12.85 x 996.4 +/- 518.8, p < 0.05), and
      a statistic tendency to this result when compared with group IV (16.2 +/- 12.85 x
      1634.2 +/- 1001.33, p = 0.063). When compared with group III, no statistical
      difference was found (16.2 +/- 12.85 x 19.8 +/- 14.81, p = NS). Episodes of VT
      and the presence of LP were noted only in groups II and IV. CONCLUSION: The group
      with concentric remodeling of the LV had fewer ventricular arrhythmias than
      hypertrophic groups, with characteristics closer to the patients with normal LV
      geometry.

PMID- 8155002
TI  - [Posttraumatic chylothorax. Experience in the postoperative period following
      cardiothoracic surgery].
AB  - PURPOSE: To report the accumulated experience in the treatment of patients with
      postoperative chylothorax (CHT) recovery utilizing pleural drainage associated to
      alipoidic diet and/or intravenous nutrition. METHODS: The aim of this work is to
      analyse the management of 11 patients (8 males; 11 months to 70 years old) with
      post-operative CHT. The previous pathologies were: congenital heart disease in 7;
      coronary insufficiency in 2; pulmonary tumor in 1 and mediastinal tumor in 1. The
      diagnosis was made up to 2nd postoperative week in 6, up to 4th week in 3 and
      later in 2 patients. The volume through the drain ranged from 200 to 3200ml/24h
      (median 636ml/24h). The laboratory diagnosis was made by lipidic presence in
      pleural effusion. In all patients the clinical management was made by hipo or
      alipoidic diet. RESULTS: In 7 the response was good with a decrease of drainage
      progressively. In 4, it was necessary the introduction of intravenous nutrition
      by the insufficient response and maintenance of drainage. The reoperation was not
      used and lymph fistula closed in a period until 10 days in 1 patient; until 20
      days in 6 and after this in 4. CONCLUSION: In conclusion, the post-operative CHT
      may be treated by thoracic drainage and alipoidic diet and/or intravenous
      nutrition with fistula closure in all patients and without need of reoperation.

PMID- 8155003
TI  - [Radiometric survey during hemodynamic studies with "Siemens Angioskop D"
      equipment].
AB  - PURPOSE: To provide data for professional specialized in these subjects,
      contributing to minimize their exposure radiation dosage. METHODS: We made a
      radiometric survey using a ionization chamber to check the exposure rate in
      several places in the examination's room to different operational conditions of X
      ray equipment. RESULTS: The operational conditions on which we have gotten the
      highest scatter X-ray rate were: image intensifier with 17cm of diameter for left
      anterior oblique projection (45 degrees) and image intensifier with 27cm of
      diameter for perpendicular beam to the patient (0 degrees). During fluoroscopy
      and cinefilm mode we have got average reduction of 40% for scatter X-ray using
      the image intensifier of 27 cm of diameter. During the cinefilm the dose rates
      were 23 times bigger than the dose rate in fluoroscopy mode. CONCLUSION: An
      analysis of results show that the choice of X-ray entrance angle as well as the
      diameter of image's intensifier during the cinefilm and fluoroscopy mode change
      significantly the occupational exposure dosages. Considering that in this kind of
      procedure, physicians and assistants spent long time close to the patient, they
      should have special concern to observe the technical condition more appropriate
      as well as to make use of all protection devices to minimize the personnel
      dosage.

PMID- 8155004
TI  - [Hypothermic retrograde cerebral perfusion for treatment of air embolism during
      extracorporeal circulation].
AB  - Air embolism during extracorporeal circulation is a life-threatening
      complication, requiring immediate response. During a recent case, brain damage
      was avoided using hypothermic retrograde cerebral perfusion, connecting the
      arterial line to superior vena cava cannula. Perfusion lasted 5 minutes at flow
      of 200ml/min. The patient had complete recovery and was discharged with normal
      neurologic status. The technique employed is described and steps for a face this
      accident are proposed.

PMID- 8155005
TI  - [Catheter ablation of ectopic incessant atrial tachycardia using radiofrequency.
      Reversion of tachycardiomyopathy].
AB  - A 8-year-old female patient with refractory incessant atrial tachycardia, very
      symptomatic and with left ventricular ejection fraction of 0.25.
      Electrophysiological study and endocardial mapping localized the site of the
      origin of atrial tachycardia in the superior right atrium. In this site 2
      applications of radiofrequency current (25V, 20 and 50 seconds) resulted in
      termination of the atrial tachycardia. She was discharged off antiarrhythmic
      drugs and after 2 months ejection fraction was 0.52. She was completely
      asymptomatic 6 months after ablation procedure.

PMID- 8155006
TI  - [Multiple myocardial coronary bridges].
AB  - White woman, 31 years old, complaint pain in the left arm, at rest, and few
      months later she had pain in the precordial region with dyspnea, diaphoresis and
      dizziness without any inducing factor. One hour later, symptoms ceased
      spontaneously, remaining daily precordial pain. Subsidiary examinations as
      cineangiocoronariography revealed 100% of arterial lumen constriction in the
      middle portion of the descending coronary artery, during systole, as well as in
      the diagnoalis and marginal branches. Multiple myocardial coronary bridges has
      been described in necropsy, but during cinecoronarioangiography, this case
      appeared to be the first one.

PMID- 8155007
TI  - [Experimental animal models and complications of transluminal coronary
      angioplasty].

PMID- 8155008
TI  - Neurophobia: the fear of neurology among medical students.

PMID- 8155009
TI  - Clone, shrink, or mutate. Residency training for the year 2000.

PMID- 8155010
TI  - Predictive value of clinical history and electrocardiogram in patients with
      transient ischemic attack or minor ischemic stroke for subsequent cardiac and
      cerebral ischemic events. The Dutch TIA Trial Study Group.
AB  - OBJECTIVE: Patients with cerebral ischemia have a high mortality rate. The most
      common cause of death is myocardial infarction. We attempted to identify risk
      factors for subsequent cardiac events in patients with cerebral ischemia by means
      of the history and electrocardiography performed with the patient at rest.
      DESIGN: The original inception cohort was entered in a multicenter randomized
      clinical trial (30 or 283 mg/d of aspirin) and followed up prospectively for a
      mean period of 2.6 years. SETTING: Patients were admitted to the hospital or seen
      in outpatient clinics. PATIENTS: Patients with one or more transient ischemic
      attacks (symptoms completely reversible within 24 hours) and patients with minor
      ischemic stroke (symptoms persisting for longer than 24 hours) were randomized,
      provided they were independent in most activities of daily living. Patients with
      a definite or probable source of embolism in the heart were excluded. A total of
      3021 patients were included in the study. Follow-up was performed at 4-month
      intervals. MAIN OUTCOME MEASURES: Primary cardiac outcome events were defined as
      nonfatal myocardial infarction and cardiac death. Cardiac death included sudden
      death, fatal myocardial infarction, or death due to congestive heart failure; 189
      patients suffered a cardiac death--82 of which were sudden deaths--or nonfatal
      myocardial infarction. RESULTS: By means of multivariate analysis, the following
      independent predictors for cardiac events were identified (hazards ratio/95%
      confidence limits): age older than 65 years (1.6/1.2 to 2.2), male sex (1.5/1.1
      to 2.1), angina pectoris (1.5/1.0 to 2.3), diabetes (1.6/1.1 to 2.5), anterior
      infarction noted on electrocardiography (1.7/1.1 to 2.7), inverted T wave noted
      on the electrocardiogram (1.6/1.1 to 2.4), and left ventricular hypertrophy noted
      on electrocardiography (3.2/2.0 to 4.9). CONCLUSIONS: The history and the
      electrocardiogram obtained with the patient at rest are valuable tools for
      cardiac risk assessment in patients with recent cerebral ischemia.

PMID- 8155011
TI  - A controlled trial of lazabemide (Ro 19-6327) in levodopa-treated Parkinson's
      disease. Parkinson Study Group.
AB  - BACKGROUND: Lazabemide (Ro 19-6327) is a short-acting, reversible, highly
      selective inhibitor of monoamine oxidase type B, that, unlike selegiline
      (deprenyl), is not metabolized to active compounds. DESIGN: A randomized, double
      blind clinical trial to assess the short-term safety and tolerability and the
      effect on motor performance of lazabemide in subjects who had Parkinson's disease
      requiring treatment with levodopa. METHODS: One hundred thirty-seven patients
      were enrolled at 14 centers and randomized to receive 100, 200, or 400 mg/d of
      lazabemide, or matching placebo. Subjects were followed up for 8 weeks, which
      included a randomized, double-blind withdrawal of lazabemide for either 2 or 4
      weeks. The primary measure of tolerability was the proportion of treated subjects
      who were able to complete the study with their originally assigned treatment.
      Clinical features were assessed by the Unified Parkinson's Disease Rating Scale.
      RESULTS: Lazabemide treatment was as well tolerated as placebo and was not
      attended by serious adverse experiences. There was a trend toward an increased
      frequency of adverse effects suggesting heightened dopaminergic activity among
      lazabemide-treated subjects. No significant improvement in the clinical features
      of Parkinson's disease was found after 4 weeks of lazabemide treatment.
      CONCLUSIONS: The overall safety of lazabemide observed in this short-term study
      justifies further long-term investigations to determine if this monoamine oxidase
      type B inhibitor is a useful adjuvant to levodopa therapy in Parkinson's disease.

PMID- 8155012
TI  - Structural and functional brain imaging in Friedreich's ataxia.
AB  - BACKGROUND: Although the major neuropathologic changes in Friedreich's ataxia
      (FA) affect the spinal cord and peripheral nerves, we previously found abnormally
      increased glucose metabolism in the cerebral hemispheres in ambulatory patients
      and a return toward normal metabolism in nonambulatory patients. OBJECTIVE: To
      determine whether brain atrophy accompanies the decline in cerebral glucose
      metabolism in FA and whether the degree of atrophy and the extent of decline in
      cerebral glucose metabolism are related to clinical severity. DESIGN: Prospective
      series. SETTING: University referral center. PATIENTS: Twenty-two patients with
      FA and 26 patients with dizziness, headache, or minor acute head trauma, serving
      as control subjects, who underwent computed tomographic scans that were
      interpreted as normal. MEASURES: In patients with FA and control subjects,
      regional atrophy was assessed using subjective and objective measures on computed
      tomographic scans. In patients with FA, local cerebral glucose metabolism was
      measured with positron emission tomography, and clinical severity was assessed
      with a clinical rating scale. RESULTS: Atrophy in the cerebral hemispheres,
      cerebellum, and brain stem was significantly greater in patients with FA than in
      control subjects, and the degree of atrophy correlated with the clinical
      severity. Local cerebral metabolic rate for glucose declined significantly from
      the initially elevated levels in the thalamus, cerebellum, and brain stem in
      correlation with increasing clinical severity. CONCLUSIONS: The structure and
      function of wide-spread brain regions including the cerebral hemispheres are
      abnormal in FA, and these abnormalities correlate with the clinical severity.

PMID- 8155013
TI  - Implicit and explicit memory in patients with Parkinson's disease with and
      without dementia.
AB  - OBJECTIVE: To study explicit and implicit memory processes in patients with
      Parkinson's disease. DESIGN: Case-control design. All subjects were given a
      neuropsychological test battery, and the test scores were compared among the
      groups. SETTING: Government-funded research facility. All subjects were examined
      as outpatients. PATIENTS: We tested nondemented (n = 13) and demented (n = 5)
      patients with Parkinson's disease and normal controls (n = 12) matched for age,
      gender, and educational level. MAIN OUTCOME MEASURES: Memory for verbal and
      pictorial stimuli under both explicit and implicit retrieval conditions. RESULTS:
      Both nondemented and demented patients with Parkinson's disease exhibited
      impairment on tests of explicit memory. Their impairment could be graded based on
      the level of effort required by the task: impaired free recall in nondemented
      patients and impaired free recall, cued recall, and recognition in demented
      patients. By contrast, neither group showed evidence of impairment on automatic
      (modality monitoring and word frequency estimation) or implicit (word and picture
      fragment identification) memory tasks. Correlation analyses did not support any
      association between the effortful memory deficits and neurologic variables, mood,
      or performance on executive function tests. CONCLUSIONS: Memory deficits in
      patients with Parkinson's disease primarily involve the conscious, effortful
      strategic aspects of searching long-term memory.

PMID- 8155014
TI  - The impact of aging on curiosity as measured by exploratory eye movements.
AB  - OBJECTIVE: To investigate changes in novelty-seeking behavior (curiosity)
      associated with normal aging. BACKGROUND: Recently, we demonstrated that patients
      with a diagnosis of probable Alzheimer's disease display diminished novelty
      seeking behavior as measured by exploratory eye movements. Nondemented, elderly
      individuals are often depicted in clinical descriptions as exhibiting diminished
      curiosity and increased disengagement from their surroundings. However, this
      behavior has not been systematically investigated as a function of normal aging.
      SETTING: University hospital center studying aging and dementia. SUBJECTS:
      Fourteen active, healthy elderly subjects (mean age, 72 years) and 16 middle-aged
      subjects (mean age, 42 years) matched for education and estimated IQ. MEASURES:
      Exploratory eye movements were recorded in response to visual stimuli that varied
      in novelty, complexity, and incongruity. RESULTS: Both older and middle-aged
      subjects (1) spent significantly more time exploring the more irregular or
      incongruous of two simultaneously presented stimuli, (2) spent increasingly less
      time looking at a repeating visual stimulus paired with a stimulus that changed
      with each trial, and (3) exhibited the same degree of overall exploration of a
      visual scene and devoted an approximately equal amount of attention to an
      unexpected element within it. As a group, older subjects spent slightly less time
      than middle-aged subjects examining incongruous stimuli. However, 71% (10/14) of
      older subjects performed within 1 SD of the mean of middle-aged subjects and 21%
      (3/14) performed as well as the top 50% (8/16) of middle-aged controls.
      CONCLUSIONS: The drive for curiosity, as measured by exploratory eye movements,
      can be well preserved in older individuals. Further research is needed to
      determine if the integrity of this drive can serve as a marker of "successful
      aging" and to identify which physiological and psychological factors influence
      its preservation through the life cycle.

PMID- 8155015
TI  - Differential but infrequent alterations of hepatic enzyme levels and thyroid
      hormone levels by anticonvulsant drugs.
AB  - OBJECTIVE: To assess the differential effects of antiepileptic drugs (AEDs) on
      hepatic enzyme and thyroid hormone levels and to assess the frequency and degree
      of these alterations. STUDY DESIGN: Retrospective analysis of hepatic enzyme
      (serum aspartate aminotransferase and alanine aminotransferase) and thyroid
      hormone (thyroxine, T uptake; and free thyroxine index) levels obtained during a
      10-year period in a large unselected outpatient population of patients with
      epilepsy. PATIENTS: Unselected (for age, sex, race, type of epilepsy, or degree
      of control) epileptic subjects (n = 642 for determination of hepatic enzyme
      levels and n = 317 for determination of thyroid hormone levels) attending the
      largest outpatient epilepsy center in the Midwest. Infants (younger than 1 year)
      and those receiving more than two AEDs were excluded. OUTCOME MEASURE: Hepatic
      enzyme and thyroid hormone level alterations vis-a-vis the type of AED, serum AED
      levels, and monotherapy vs bitherapy. RESULTS: Aspartate aminotransferase level
      alterations were mainly due to valproate or phenobarbital, and alanine
      aminotransferase alterations were due to phenytoin. Significant enzyme level
      elevations were infrequent (2% [14/642] of patients), mild, usually associated
      with bitherapy, transient, and confined to aspartate aminotransferase level.
      Persistent elevations of both aspartate aminotransferase and alanine
      aminotransferase levels occurred in only one patient, and he had underlying liver
      disease. Phenytoin was most and phenobarbital least likely to influence the
      thyroid indexes. Although bitherapy was more likely to produce biochemical
      alterations of thyroid hormone levels compared with monotherapy, clinically
      significant thyroid hormone level alterations were seen in only one of 317
      patients, and this patient was known to have hypothyroidism. CONCLUSIONS:
      Antiepileptic drugs affect hepatic enzyme and thyroid hormone levels
      differentially, and bitherapy alters them more than monotherapy does. However,
      alterations are mostly mild and clinically insignificant and do not justify
      routine testing, except in those known to have a coexisting hepatic or thyroid
      abnormality, those who develop symptoms of hepatic or thyroid involvement while
      receiving AEDs, and perhaps those receiving bitherapy with high serum AED levels.

PMID- 8155016
TI  - Facioscapulohumeral muscular dystrophy in early childhood.
AB  - OBJECTIVE: To determine the occurrence and the clinical and genetic variability
      of early-onset facioscapulohumeral muscular dystrophy (FSHD). DESIGN: Patients
      were derived from a large series of patients who participated in a genetic study
      of FSHD in the Netherlands. PATIENTS: A group of 96 patients of 17 families with
      autosomal dominant FSHD, nine sporadic cases of FSHD, and 35 children at risk for
      having the FSHD gene was searched for the presence of early-onset cases. Criteria
      for early-onset FSHD were (1) signs or symptoms of facial weakness before the age
      of 5 years and (2) signs or symptoms of shoulder girdle weakness before the age
      of 10 years. RESULTS: Six early-onset cases (four familial, two sporadic) were
      identified. Four of five cases showed an abnormal DNA fragment with the probe
      p13E-11, which has been shown to detect DNA rearrangements in FSHD patients. The
      clinical symptoms in these early-onset cases showed great variability with
      respect to rate of progression of muscle weakness, the association of hearing
      loss and retinopathy, and the expression of the disorder in parents and siblings.
      CONCLUSIONS: Infantile FSHD has been suggested to be a separate form of the
      disease, often accompanied by sensorineural hearing loss and retinal
      telangiectasia. Our findings, as well as the fact that both hearing loss and
      retinal vasculopathy have been recently shown to be part of FSHD, suggest that
      early-onset FSHD is not a separate entity, but part of a wide clinical spectrum
      of FSHD.

PMID- 8155017
TI  - D2 dopamine receptor alleles do not influence severity of Tourette's syndrome.
      Results from four large kindreds.
AB  - OBJECTIVE: We investigated the recently proposed hypothesis that the A1 allele of
      the Taq I polymorphic system at the D2 dopamine receptor gene (DRD2) influences
      the severity of Tourette's syndrome (TS). We have previously demonstrated that
      DRD2 is not linked to TS, establishing that it cannot be the major locus
      determining the susceptibility to develop TS. METHOD: We studied alleles at the
      DRD2 A system in patients with TS or chronic multiple tics in four extended
      kindreds segregating TS. If this allelic system at DRD2 is associated with
      severity of TS, then among affected family members, those with the A1 allele
      should have more severe disease than those without it. Severity of disease was
      compared in affected members of the kindreds with A1 alleles and in those without
      A1 alleles. RESULTS: We evaluated disease severity in two ways. First, we
      evaluated 17 individuals from two families using a derivative of the Yale Global
      Tic Severity Scale composed of subscales concerning number, frequency, and
      severity of motor and phonic tics, rated separately. We divided this sample (n =
      17, nine with TS and eight with chronic multiple tics) by genotype at the A1/A2
      system. The heterozygotes (n = 7) had an average severity score of 11.3; the A2
      homozygotes had an average severity score of 14.2. (There were no A1
      homozygotes.) Second, we evaluated 47 individuals from two different families
      (all with TS) using the TS symptomatology evaluation. We compared severity scores
      for these individuals by genotype at the A1/A2 system. The heterozygotes (n = 24)
      had a mean severity score of 3.0, and the A2 homozygotes (N = 21) had a mean
      severity score of 3.7. CONCLUSION: Our data do not support alleles at the A
      system of DRD2 as a factor associated with severity of TS.

PMID- 8155018
TI  - Sparing of motor function after cortical injury. A new perspective on underlying
      mechanisms.
AB  - Historically, many theories have been offered to explain recovery of function
      following permanent brain injury. Because specific functional deficits often
      occur after injury to certain neuroanatomical locations, it has been tempting to
      suggest that within the brain, structure equals function (this interpretation, of
      course, has its roots in "phrenology", the 19th-century practice of detecting
      mental and behavioral traits by examining the skull's shape). Views that were
      common until recently emphasized structural and functional rigidity in the brain,
      which would seem to provide little opportunity for the occurrence of
      compensation. However, the observation that a considerable amount of spontaneous
      functional recovery occurs after many permanent brain lesions requires some
      explanation for the recovery that involves modification of intact portions of the
      brain. Recent research has provided data that reveal several forms of brain
      plasticity, including changes in neurotransmitter sensitivity, collateral
      sprouting, and diaschisis. Evidence supporting claims that beneficial behavioral
      recovery occurs through such physiological modifications in the brain are
      abundant in the literature, although, in general, there has not been any
      empirical establishment of causality.

PMID- 8155019
TI  - Carpal tunnel syndrome and hand-arm vibration syndrome. A diagnostic enigma.
AB  - OBJECTIVE: This article serves to draw attention to the risk to workers from
      repetitive strain and hand-arm vibration in the workplace and to the diagnostic
      difficulty in distinguishing carpal tunnel syndrome from the sensorineural
      component of hand-arm vibration syndrome. DATA SOURCES: Journal publications,
      textbooks on hand-arm vibration, guidelines of the International Standards
      Organisation, and European Economic Community directives. STUDY SELECTION: Recent
      reports and current standards. CONCLUSION: Carpal tunnel syndrome can be
      distinguished from hand-arm vibration syndrome if all factors--anatomical,
      associated physiological and medical conditions, work exposure history, and ulnar
      nerve involvement--are evaluated. In some circumstances, the conditions may be
      present together. A correct diagnosis is crucial because surgical intervention is
      not usually beneficial if hand-arm vibration exposure has been a contributing
      factor. The further reduction in grip strength may constitute a serious
      additional handicap for a worker.

PMID- 8155020
TI  - Progressive multifocal leukoencephalopathy complicating Wiskott-Aldrich syndrome.
      Report of a case and review of the literature of progressive multifocal
      leukoencephalopathy with other inherited immunodeficiency states.
AB  - OBJECTIVE: To describe the occurrence of progressive multifocal
      leukoencephalopathy (PML) in association with Wiskott-Aldrich syndrome, an X
      linked recessive disorder with impairment of both cellular and humoral immunity.
      DESIGN: A detailed analysis of this patient's clinical illness, immunologic
      factors, neuroradiographic findings, and brain histopathologic conditions was
      undertaken. The medical literature on PML complicating congenital immunodeficient
      states was also reviewed. SETTING: A 1500-bed, university-affiliated, public
      health hospital. PATIENT: A 15-year-old boy with Wiskott-Aldrich syndrome. His
      neurologic illness was heralded by dysarthria and right-sided weakness and the
      diagnosis was established by brain biopsy specimen. Survival from the time of
      onset of PML was 10 months. CONCLUSION: Although PML typically occurs in the
      setting of severe acquired cellular immunodeficiency, often as a consequence of
      acquired immunodeficiency syndrome, organ transplantation, and leukemia and
      lymphoma, it may rarely accompany inherited immunodeficiency syndromes. The
      reported childhood cases of PML include three patients, aged 5, 11, and 18 years,
      with other inherited immunodeficiency syndromes. This patient represents the
      first time (to our knowledge) that PML has been reported to occur in association
      with Wiskott-Aldrich syndrome.

PMID- 8155021
TI  - Optic nerve sheath fenestration for treatment of progressive ischemic optic
      neuropathy.

PMID- 8155022
TI  - Spontaneous improvement of progressive anterior ischemic optic neuropathy.

PMID- 8155023
TI  - Is informed consent needed for fluorescein angiography?

PMID- 8155024
TI  - Hyperbaric oxygen and acetazolamide improve visual acuity in patients with
      cystoid macular edema by different mechanisms.

PMID- 8155025
TI  - Lack of effect of peripheral laser iridotomy in pigment dispersion syndrome.

PMID- 8155026
TI  - Acute retinal necrosis after chickenpox in a patient with acquired
      immunodeficiency syndrome.

PMID- 8155027
TI  - Cicatricial ectropion: a complication of systemic fluorouracil.

PMID- 8155028
TI  - The cost-effectiveness of restoring sight.

PMID- 8155029
TI  - The ischemic optic neuropathy decompression trial.

PMID- 8155030
TI  - The FDA and its regulation of ophthalmic devices.

PMID- 8155031
TI  - Comparison of excimer laser treatment of astigmatism and myopia. The Excimer
      Laser and Research Group.
AB  - OBJECTIVE: To assess the safety and efficacy of excimer laser treatment of myopic
      astigmatism and to compare this with the excimer laser treatment of myopia.
      DESIGN: A prospective, open study of consecutive patients having excimer laser
      treatment of myopic astigmatism or myopia. SETTINGS: Patients were recruited from
      18 private ophthalmic practices. PATIENTS: Fifty-four eyes received treatment for
      astigmatism and 66 eyes for myopia. One patient was lost to follow-up, and
      another underwent an ineffective ablation. INTERVENTIONS: A VISX Twenty/Twenty
      excimer laser was used to perform either photoastigmatic refractive keratectomy
      or photorefractive keratectomy. MAIN OUTCOME MEASURES: Refraction and visual
      acuity with and without correction were assessed preoperatively and
      postoperatively. RESULTS: At 6 months, 17 (85%) of the 20 patients receiving
      photoastigmatic refractive keratectomy were within 1 diopter of plano refraction,
      and 19 (95%) of 20 had uncorrected visual acuity of 6/12 (20/40) or better. For
      patients receiving photorefractive keratectomy, these figures were 28 (88%) of 32
      patients and 28 (88%) of 32 patients, respectively. CONCLUSIONS: Excimer laser
      surgery offers an effective option in the treatment of myopic astigmatism.

PMID- 8155032
TI  - The correction of high myopia using the excimer laser.
AB  - OBJECTIVE: To determine the safety and efficacy of excimer laser photoablation as
      a treatment to correct high myopia that is defined as a spherical equivalent
      refractive error greater than -8.00 diopters (D). DESIGN: Using a multizone (4.0
      , 5.0-, and 6.0-mm) photorefractive keratectomy protocol for correction of high
      myopia, 23 eyes in 18 patients were treated at one clinical center with an
      excimer laser (VISX Inc, Santa Clara, Calif). Preoperative spherical equivalent
      refractions ranged from -8.00 to -19.50 D (mean +/- SD, -11.83 +/- 2.92 D); the
      mean attempted ablation depth was 93.0 +/- 20.2 microns. RESULTS: At the last
      postoperative examination (mean +/- SD, 7.5 +/- 3.7 months), the mean +/- SD
      spherical equivalent refraction was -1.09 +/- 2.08 D, including results from two
      repeated procedures; visual acuity in 52% of the eyes was 20/40 or better
      uncorrected; 65% of the eyes improved or did not change best corrected acuity,
      whereas two eyes lost 2 Snellen lines; 39% of the eyes were +/- 1.00 D; and 65%
      were +/- 2.00 D of attempted correction. Corneal haze (corneal clarity score of >
      or = 1.5) was observed in 47% of the eyes at some time postoperatively.
      CONCLUSIONS: Photorefractive keratectomy for high myopia was found to be not
      nearly as efficient or predictable as it is for low myopia. A greater incidence
      of regression of refractive effect and corneal haze were noted in these cases
      compared with reported studies of low to moderate myopia. A multizone approach to
      reduce ablation depth during photorefractive keratectomy for myopia that is
      greater than 8.00 D does not appear to prevent subsequent haze or refractive
      regression.

PMID- 8155033
TI  - Prospective evaluation of the effect of pseudophakic cystoid macula edema on
      contrast sensitivity.
AB  - OBJECTIVE: To evaluate the effect of pseudophakic cystoid macular edema (PCME) on
      contrast sensitivity. DESIGN: Best-corrected visual acuity, fluorescein
      angiogram, and contrast sensitivity measurements were obtained before surgery and
      at 8 weeks and 8.5 months after surgery. Eyes were classified as having no PCME,
      transient PCME, or persistent PCME. PARTICIPANTS: The study population consisted
      of 31 consecutive patients undergoing extracapsular cataract extraction with
      posterior chamber intraocular lens implantation between September 1990 and March
      1991. MAIN OUTCOME MEASUREMENTS: Outcomes were best-corrected visual acuity and
      contrast sensitivity. RESULTS: Analysis of variance showed a significant decrease
      for all spatial frequencies at 8 weeks (P < .005) and for higher frequencies at
      8.5 months (P < .05) in both PCME groups and for higher frequencies at 8 weeks in
      the transient PCME group. CONCLUSION: Decrease in contrast sensitivity associated
      with PCME may account for persistent visual difficulties despite good Snellen
      visual acuity.

PMID- 8155034
TI  - Rebound of macular edema with continued use of methazolamide in patients with
      retinitis pigmentosa.
AB  - PURPOSE: To assess the effect of methazolamide on chronic macular edema in
      patients with retinitis pigmentosa in a double-masked, placebo-controlled,
      crossover study. Three subjects who had an initial improvement in their macular
      edema as demonstrated on fluorescein angiography received a continued course of
      methazolamide to assess its effect on macular edema. METHODS: Seventeen subjects
      were enrolled in the initial study. On angiography, nine subjects demonstrated
      improvement in their macular edema with the use of methazolamide for 3 weeks;
      three of these continued receiving the drug at a dosage of 50 mg twice daily for
      either an additional 6 (one subject) or 12 (two subjects) weeks. All subjects
      were assessed at each visit with fluorescein angiography and on best corrected
      visual acuity, both undilated and dilated; a subjective impression was also
      documented. RESULTS: After 6 and 12 weeks of treatment, all three subjects
      experienced a rebound of angiographic macular edema to some extent. The visual
      acuity varied only slightly (up to 7 letters) from both the baseline and most
      recent examinations after 6 and 12 weeks of treatment. CONCLUSION: Results from
      these few subjects suggest that at least a partial rebound of macular edema seen
      angiographically may occur with the continued use of methazolamide in patients
      with retinitis pigmentosa and chronic macular edema. Further study is required to
      determine if this rebound effect also occurs in treatment of other ocular
      disorders with chronic macular edema.

PMID- 8155035
TI  - Pentoxifylline increases retinal capillary blood flow velocity in patients with
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to determine whether oral pentoxifylline
      would improve retinal microvascular hemodynamics and blood rheology in patients
      with diabetes. DESIGN: Patients were enrolled in a double-masked, placebo
      controlled trial of pentoxifylline at 2000 mg/d. Retinal capillary blood velocity
      and leukocyte density, filterability, viscosity, and fibrinogen content were
      measured by the blue-field entoptic phenomenon simulation, filtration, rotational
      viscosimetry, and heat precipitation techniques, respectively, before, during,
      and after drug therapy. RESULTS: Treatment with pentoxifylline resulted in a
      23.2%, 26.8%, and 37.8% increase in capillary blood flow velocity at 1, 2, and 3
      months of therapy, respectively, with a return to pretreatment baseline levels 1
      month after cessation of therapy. There were no apparent effects on the remaining
      variables during treatment. CONCLUSION: Pentoxifylline increases retinal
      capillary blood flow velocity in patients with diabetes.

PMID- 8155036
TI  - Surgical effects of trabeculotomy ab externo on adult eyes with primary open
      angle glaucoma and pseudoexfoliation syndrome.
AB  - OBJECTIVES: Retrospective and prospective studies examined the surgical effects
      in lowering intraocular pressure levels of trabeculotomy ab externo in adult eyes
      with either primary open angle glaucoma or pseudoexfoliation syndrome. We report
      the results of primary trabeculotomy as an intervention for glaucoma. PATIENTS:
      Included in the retrospective study were 357 eyes of 227 patients with primary
      open angle glaucoma and 82 eyes of 65 patients with pseudoexfoliation syndrome,
      each of which underwent trabeculotomy ab externo alone and none of which had a
      history of laser or surgical treatment for ocular disease. Included in the
      prospective study were 33 eyes of 22 patients with primary open angle glaucoma
      and 17 eyes of 15 patients (older than 40 years) with pseudoexfoliation syndrome.
      RESULTS: A life-table analysis for the retrospective study showed that the final
      success probability (mean +/- SE) at 5 years after surgery was 73.5% +/- 6.3% in
      eyes with pseudoexfoliation syndrome, which is significantly better than 58.0% +/
      3.1% in eyes with primary open angle glaucoma (P < .05). Also, the higher the
      preoperative intraocular pressure levels are, the less likely that the
      postoperative intraocular pressure levels will be brought under control (P <
      .01). Surgical outcome in the prospective study demonstrated success in 27 (79%)
      of 34 eyes after 3 years and in 16 (64%) of 25 eyes after 5 years, with
      medication. Complications included Descemet's membrane detachment (one eye),
      cyclodialysis (one eye), and decreased visual acuity due to progression of
      cataract (four eyes). CONCLUSION: The surgical results of trabeculotomy ab
      externo remain effective in controlling intraocular pressure levels for a long
      time in selected patients. It thus appears that trabeculotomy ab externo can be
      considered as an alternative choice of surgical treatment in some cases of
      glaucoma.

PMID- 8155037
TI  - Alveolar rhabdomyosarcoma that metastasized to the orbit.
AB  - A 22-year-old woman with a history of hyperthyroidism and a paravaginal alveolar
      rhabdomyosarcoma developed diplopia 3 months after successful autologous bone
      marrow transplantation. Results of computed tomographic scan showed apparent
      enlargement of the right inferior rectus muscle, and thyroid eye disease was
      suspected. However, results of further evaluation revealed an alveolar
      rhabdomyosarcoma that metastasized to the orbit.

PMID- 8155038
TI  - Incidence of ulcerative keratitis in a defined population from 1950 through 1988.
AB  - OBJECTIVE: To determine the incidence of ulcerative keratitis and to assess
      trends in risk factors leading to ulcerative keratitis. DESIGN: Retrospective
      incidence cohort study. SETTING: General community. PATIENTS: Population-based
      sample of residents of Olmsted County, Minnesota, in the 39-year period between
      1950 and 1988. MAIN OUTCOME MEASURE: Cases of ulcerative keratitis. RESULTS: One
      hundred forty-one cases of ulcerative keratitis were diagnosed among 131
      residents (64 men and 67 women) of Olmsted County. The mean annual age-adjusted
      incidence per 100,000 people was 5.3 (95% confidence interval, 4.4 to 6.2). A
      435% increase in the incidence of ulcerative keratitis was observed in Olmsted
      County residents from the 1950s (2.5 per 100,000 people) to the 1980s (11.0 per
      100,000 people) (P = .001). The cases of ulcerative keratitis associated with
      contact lens wear increased from 0% in the 1950s and 1960s to 32% in the 1970s
      and 52% in the 1980s. CONCLUSION: The incidence of ulcerative keratitis has
      increased significantly in this community. Contact lens wear was the most
      important risk factor for the development of ulcerative keratitis during the last
      decade.

PMID- 8155039
TI  - Amplitudes of accommodation of primate lenses refilled with two types of
      inflatable endocapsular balloons.
AB  - OBJECTIVE: To investigate the maintenance of ocular accommodation by refilling
      the lenses of the eyes of youthful primates with inflatable endocapsular
      balloons. METHODS: The lenses of 21 cynomolgus monkeys were refilled following
      endocapsular phacoemulsification with a balloon that either approximates the
      shape of the non-accommodated lens or the accommodated crystalline lens. RESULTS:
      In nine of 15 successfully refilled lenses, we were able to perform automated
      refractometry to determine the amplitude of accommodation, ie, changes in
      refraction before and 1 hour after application of topical 4% pilocarpine
      hydrochloride to alter lens shape. At 2 weeks, 2 to 3 months, and 6 to 12 months
      after operation, mean (+/- SD) accommodation was 4.6 +/- 2.5, 2.5 +/- 0.5, and
      1.7 +/- 0.7 diopters (D), respectively, in the lenses refilled with the
      nonaccommodation balloon (n = 5; preoperative value, 15.2 +/- 1.3 D), and it was
      1.9 +/- 0.5, 1.3 +/- 0.9, and 1.8 +/- 0.9 D, respectively, in the lenses refilled
      with the accommodation balloon (n = 4; preoperative value, 17.0 +/- 2.9 D).
      CONCLUSION: The greater yield of accommodation with the nonaccommodation balloon
      is consistent with the recent theory on the mechanism of accommodation. Although
      the obtained accommodation was a small fraction of values determined prior to the
      operation and the small amplitude of accommodation decreased over time, the
      feasibility of refilling the lens with an inflatable endocapsular balloon,
      allowing at least some accommodation in the eyes of youthful primates, was
      demonstrated. Applied to humans, this procedure may allow accommodation following
      cataract surgery.

PMID- 8155041
TI  - The nervus intermedius.

PMID- 8155040
TI  - Anterior capsule opacification in monkey eyes with posterior chamber intraocular
      lenses.
AB  - OBJECTIVE: To examine the morphologic features of anterior capsule opacifications
      in pseudophakic monkey eyes. METHODS: Extracapsular lens extraction with
      implantation of posterior chamber intraocular lenses in six monkey eyes. Eyes
      were enucleated 2, 4, and 12 months after implantation and then studied with
      light and electron microscopy. Distribution of proteoglycans was also examined
      with cuprolinic blue staining. RESULTS: Anterior capsule opacifications were
      composed of proliferated cellular and extracellular matrix components situated
      between the anterior capsule and the optics of the intraocular lens. The
      morphologic features of the proliferated cells were consistent with epithelial
      cells, and these cells probably represented lens epithelial cells. The
      extracellular matrix, which consisted of collagen fibrils, basal lamina-like
      material, and microfibrils, was most prominent in the specimens obtained 12
      months after lens implantation. The extracellular matrix contained proteoglycans
      that showed positive staining with cuprolinic blue. CONCLUSIONS: Anterior capsule
      opacifications consisted of proliferated lens epithelial cells and aberrant
      extracellular matrix.

PMID- 8155042
TI  - Identifying the ciliary sulcus for suturing a posterior chamber intraocular lens
      by transillumination.
AB  - We describe herein a technique for locating the ciliary sulcus for suturing a
      posterior chamber intraocular lens. Transscleral illumination with a light-guide
      fiber placed underneath the iris reveals the ciliary sulcus as a bright area near
      the limbus, and it allows for a straight needle with 10-0 polypropylene fiber to
      be easily inserted through the sulcus after making two pairs of radial scleral
      incisions to fixate the 10-0 polypropylene fiber. We think that this procedure
      can minimize complications of suturing a posterior chamber intraocular lens and
      shorten the operation time.

PMID- 8155043
TI  - Atypical presentations of macular holes.

PMID- 8155044
TI  - Initial argon laser trabeculoplasty to the inferior vs superior half of
      trabecular meshwork.

PMID- 8155045
TI  - Needle-assisted scleral fixation suture technique for relocating posteriorly
      dislocated intraocular lenses.

PMID- 8155046
TI  - Video imaging of the meibomian gland.

PMID- 8155047
TI  - Primary B-cell lymphoma of the eyes and brain in a 3-year-old boy.

PMID- 8155048
TI  - Bilateral extraocular muscle metastases in Zollinger-Ellison syndrome.

PMID- 8155049
TI  - Universal coverage and preventable blindness.

PMID- 8155050
TI  - Pattern reversal visual evoked potentials following early treatment of
      unilateral, congenital cataract.
AB  - OBJECTIVE: To describe the pattern reversal visual evoked potentials (VEPs) that
      were used to monitor and quantify early visual development following treatment
      for dense, unilateral, congenital cataract. DESIGN: Longitudinal prospective
      study. PATIENTS: Six infants who underwent surgery and contact lens correction
      before age 5 months and who had good compliance with occlusion therapy throughout
      the first 3 years of life. RESULTS: Initially, VEPs from aphakic eyes showed
      marked abnormalities, including small amplitudes, prolonged latencies, missing
      components, and absent VEPs to small check sizes. Threshold check size was
      elevated by 3 octaves or more. With part-time occlusion of the opposite eye, VEPs
      normalized rapidly in the first year, but residual deficits remained to age 4
      years when visual acuities were between 20/50 and 20/120 in aphakic eyes.
      Threshold check size clearly differentiated between aphakic and normal eyes and
      was the only VEP parameter that was correlated with single-letter visual acuity.
      Thus, threshold check size had greater clinical use than measures of pattern VEPs
      based on latency, amplitude, or waveform. CONCLUSIONS: Patients treated for
      unilateral congenital cataract, who have early surgery and contact lens
      correction and comply with occlusion therapy, show a period of rapid VEP
      maturation and have a good visual prognosis.

PMID- 8155051
TI  - Previously undiagnosed lymphoma presenting as recurrent dacryocystitis.
AB  - Lymphoma occurring in the lacrimal sac is uncommon and usually occurs in patients
      with known systemic disease. We report the case of an 82-year-old woman who
      presented with recurrent right dacryocystitis and a mass in the left lower
      eyelid. The results of the biopsy of the eyelid and fine-needle aspiration of the
      swelling arising from the lacrimal fossa demonstrated low-grade B-cell non
      Hodgkin's lymphoma. This unusual presentation and the histopathological features
      are described.

PMID- 8155052
TI  - Observations on seven cases of intraocular leiomyoma. The 1993 Byron Demorest
      Lecture.
AB  - A review of seven cases of intraocular leiomyoma personally managed by the
      authors disclosed clinical and histopathologic characteristics that serve to
      differentiate this uncommon tumor from uveal melanoma. Leiomyoma generally occurs
      in younger patients and has a definite predilection for females. It tends to
      affect the ciliary body and peripheral choroid rather than the posterior choroid.
      In contrast to melanoma, which is located in the uveal stroma, leiomyoma usually
      is located in the supraciliary or suprachoroidal space. During transillumination,
      leiomyoma usually transmits light readily, whereas most melanomas cast a shadow.
      If intraocular leiomyoma is suspected clinically, the best management seems to be
      removal by a modified lamellar sclerouvectomy. In contrast to melanoma, leiomyoma
      shows positive immunoreactivity for muscle markers and negative immunoreactivity
      for melanoma-specific antigen and neural markers.

PMID- 8155053
TI  - Mitomycin and the human corneal endothelium.
AB  - OBJECTIVE: To investigate the ultrastructural and physiologic effects of exposure
      of the human corneal endothelium to mitomycin at concentrations of 20
      micrograms/mL and 200 micrograms/mL using electron microscopy and in vitro
      specular perfusion techniques. METHODS: Four pairs of corneas (with one cornea of
      each pair receiving balanced salt solution [BSS Plus, Alcon Laboratories, Fort
      Worth, Tex] and the other receiving BSS Plus with 20 micrograms/mL of mitomycin)
      suitable for transplantation, except for extremes of age or systemic disease,
      underwent perfusion with corneal thickness measured serially every 15 minutes
      followed by fixation for electron microscopy. Mean corneal swelling rate was
      calculated for all four experiments, and the control group that received BSS Plus
      was compared with the group that received mitomycin using a paired t test.
      Electron micrographs were examined in a masked fashion. Similar studies were
      performed using two pairs of corneas that received 200 micrograms/mL of
      mitomycin. RESULTS: The mean swelling rate for corneas perfused with 20
      micrograms/mL of mitomycin (-4.1 microns/h) was not significantly different from
      that seen in tissue perfused with BSS Plus (-4.2 microns/h). No consistent
      ultrastructural changes could be attributed to exposure to 20 micrograms/mL of
      mitomycin. Perfusions of mitomycin at 200 micrograms/mL resulted in prompt
      corneal swelling with marked ultrastructural alterations compared with tissue
      perfused with BSS Plus. CONCLUSION: Human corneal endothelium may be exposed to
      undiluted (200 to 500 micrograms/mL) mitomycin with inadvertent entry into the
      anterior chamber during dissection of the scleral flap bed in trabeculectomy
      followed by application of mitomycin. This will result in prompt destruction of
      the endothelium. Exposure to 20 micrograms/mL of mitomycin, a level exceeding the
      concentration that may be present in the aqueous humor after its proper
      application, appears nontoxic in this system.

PMID- 8155054
TI  - The role of nitric oxide in uveitis.
AB  - OBJECTIVE: To evaluate the possible role played by nitric oxide in the
      pathogenesis of uveitis. METHODS: Uveitis was induced in rats with subcutaneous
      lipopolysaccharide. Lipopolysaccharide stimulates nitric oxide production from L
      arginine. The animals were treated with NG-nitro-L-arginine methyl ester, an L
      arginine analogue acting as a specific inhibitor of nitric oxide synthesis.
      Ocular inflammation was evaluated by measuring protein concentration and
      leukocyte number in the aqueous humor of one eye, and by histopathologic
      examination of the contralateral eye. RESULTS: Aqueous humor protein levels were
      reduced 73% to 82% and cellular infiltration was almost abrogated in NG-nitro-L
      arginine methyl ester-treated rats compared with controls. The histopathologic
      examination also showed a similar inhibition of uveal tissue inflammation in
      treated rats. CONCLUSION: By inhibiting nitric oxide synthesis, NG-nitro-L
      arginine methyl ester inhibits the induction of endotoxin-induced uveitis in the
      rat. This observation demonstrates that nitric oxide is an important mediator of
      anterior uveitis in this model system and suggests that nitric oxide may also be
      implicated in human uveitis.

PMID- 8155055
TI  - Spontaneous resolution of an extensive detachment of Descemet's membrane
      following phacoemulsification.

PMID- 8155056
TI  - An illuminating laser probe for vitreoretinal surgery.
AB  - We have developed a new multifunction instrument for use during bimanual
      vitreoretinal surgery. The illuminating laser probe provides the functions of
      endolaser photocoagulation and fiberoptic illumination in a single 19- or 20
      gauge instrument. The probe can be coupled to standard laser and illumination
      sources, and it simplifies endophotocoagulation in select surgical settings.

PMID- 8155057
TI  - Do nonclinical checkers exhibit deficits in cognitive control? Tests of an
      inhibitory control hypothesis.
AB  - We tested the hypothesis that persons who engage in compulsive checking may do so
      to compensate for cognitive errors produced by deficient inhibitory control. In
      two experiments, undergraduates were classified by scores on the MOCI checking
      subscale as checkers or noncheckers. On self-report measures, checkers were
      significantly more depressed, more anxious, more prone to cognitive slips, and
      more likely to engage in obsessive-compulsive behaviors. However, checkers
      performed similarly to noncheckers on laboratory tests of inhibitory control of
      cognition. Checkers and noncheckers were equally able to (1) ignore distractors
      in a selective attention task, (2) suppress inappropriate word meanings in a
      sentence comprehension task, and (3) inhibit retrieval of to-be-forgotten items
      in a memory task. These results suggest that compulsive checking does not arise
      from failures of inhibitory control of cognition.

PMID- 8155058
TI  - Thought suppression and smoking cessation.
AB  - Deliberate suppression of intrusive thoughts has previously been shown to be
      associated with higher levels of intrusion compared to monitoring without
      suppression. In an attempt to apply this paradigm to people attempting smoking
      reduction and cessation, it was demonstrated that intrusive thoughts about
      smoking occur frequently. Subjects reported difficulty in controlling smoking
      related intrusions, and ratings indicated that all subjects made attempts to
      suppress them. In an experimental study, instructions to suppress were associated
      with increased frequency of intrusion compared to the control (mention)
      condition. A simple distracting task was highly effective in reducing intrusion
      frequency to below the levels obtained in the control condition, and intrusions
      remained significantly lower during the second (non-suppression) period.

PMID- 8155059
TI  - Long-term monitoring of psychosocial stress and symptomatology in inflammatory
      bowel disease.
AB  - Eleven subjects with inflammatory bowel disease (IBD) participated in a longterm
      self-monitoring investigation of the relationship between psychosocial stress and
      IBD symptomatology. Two measurement instruments, the IBD Symptom Diary and the
      Psychosocial Stress Diary, were completed by each subject for 7 consecutive days
      each month for one year. Pooled time-series analysis of the influence of daily
      stress on IBD activity revealed a significant effect. A positive concurrent
      relationship was found between both daily and monthly psychosocial stress and IBD
      activity. Investigations of temporal relationship among variables revealed a
      negative effect of previous month stress on IBD. Results suggest a monthly
      rebound effect whereby IBD symptom severity is negatively responsive to the
      severity of the previous month stress. The effects of stress upon IBD were not
      found to be modified by behavioral coping strategies. These results support the
      prevailing impression that psychosocial stress contributes to the clinical course
      of IBD, and specifically suggest an influential role of daily and monthly stress.
      A pattern matching IBD's characteristic waxing and waning clinical course emerges
      when the association between stress and IBD is examined from a monthly viewpoint.
      Refinement of our knowledge of the IBD-stress model calls for replication and
      explanation of the monthly rebound effect as well as investigations into type of
      stressor and coping strategy that may influence IBD activity.

PMID- 8155060
TI  - The relationship between anxiety and memory biases for material that has been
      selectively processed in a prior task.
AB  - Despite evidence for a broad range of processing biases for threat-related
      material associated with anxiety, there is relatively little research which
      demonstrates such biases in memory in anxious individuals. The present paper
      reports two methodologies which demonstrate selective processing of threat
      related stimuli in anxious subjects. These are a homophone spelling task and an
      anagram solution task. Both paradigms require subjects to somehow 'generate' the
      threat-related material. Despite such selective processing, subsequent recall and
      recognition memory tests for the same material revealed no evidence of a memory
      bias. The clinical and theoretical implications of the data are discussed.

PMID- 8155061
TI  - Familial aggregation of panic in nonclinical panickers.
AB  - Despite several methodological difficulties inherent in the nonclinical panic
      literature, some researchers have highlighted the consistent finding that a
      greater proportion of panickers than nonpanickers report a history of panic in
      first-order relatives to be supportive of the validity of nonclinical panic
      research findings. However, in all of these studies, familial aggregation
      differences have been evaluated via panickers' and nonpanickers' self-reports of
      familial panic history. Given evidence that questionnaire assessment of panic
      results in substantial false positives (Brown & Cash, 1989, Journal of Anxiety
      Disorders, 3, 139-148), it was hypothesized that familial aggregation differences
      could be largely attributable to this phenomenon as well. Consistent with this
      hypothesis, as in prior studies, a significantly greater proportion of panickers
      than nonpanickers reported first-order relatives who experienced panic; however,
      panickers and nonpanickers also differed in their reports of close male friends
      and close female friends who had experienced panic. On the basis of these data,
      potential caveats to prior conclusions concerning familial aggregation
      differences between nonclinical panickers and nonpanickers are discussed as are
      methodological considerations for future nonclinical panic research.

PMID- 8155062
TI  - Subjective symptoms and cardiac reactivity to brief hyperventilation in
      individuals with high anxiety sensitivity.
AB  - Cognitive models maintain that panic attacks may be initiated by fear resulting
      from the interpretation of somatic sensations as personally threatening or
      harmful. Similarly, several researchers have proposed that the enhanced response
      of panickers to biological challenge may result from the fear of induced anxiety
      sensations rather than from direct stimulation of aberrant biochemical systems.
      The present study examined the effects of both panic history and fear of anxiety
      sensations on subjective and cardiac responses to biological challenge. Eighty
      nonclinical subjects were chosen on the basis of level of anxiety sensitivity and
      history of previous panic attacks. High and low anxiety-sensitive panickers and
      nonpanickers (four groups of 20 subjects) were subjected to a 90 sec period of
      voluntary hyperventilation, during which heart rate was assessed. Regardless of
      panic history, total symptom scores did not differ between high and low anxiety
      sensitive subjects at baseline or pre-hyperventilation, but did differ at post
      hyperventilation. There were, however, no significant differences in post
      hyperventilation measures of heart rate. The apparent mismatch of subjective and
      physiological responsivity to the challenge in high anxiety-sensitive individuals
      (i.e. more severe symptom self-reports in the absence of increased cardiac
      activation) provides support for the hypothesis that high anxiety sensitivity is
      associated with an enhanced tendency to panic in response to biological
      challenge.

PMID- 8155063
TI  - Selective processing of emotional information in obsessive compulsive disorder.
AB  - Three possible explanations for attentional bias effects in anxious subjects have
      been formulated: the threat-relatedness hypothesis, the emotionality hypothesis
      and the concern-relatedness hypothesis. In order to investigate these three
      hypotheses, an experiment was carried out with 33 obsessive compulsive (OC)
      patients and 29 normal controls. Both groups colour-named a Stroop card with 5
      word sets: neutral words and 4 emotional word sets (a 2 x 2 matrix of words,
      related/unrelated to obsessive compulsive disorder and positively/negatively
      valenced). In line with previous studies, OC patients selectively attended to
      negative OC-related cues; this supports the threat-relatedness hypothesis.
      Although the set-up of the experiment was similar to the Mathews and Klug (1993,
      Behaviour Research and Therapy, 31, 57-62) study, no evidence was found for the
      concern-relatedness hypothesis, i.e. the OC patients did not show an attentional
      bias for positive OC-related words. Two possible reasons for these contradicting
      findings are discussed.

PMID- 8155064
TI  - Information processing in post-traumatic stress disorder.
AB  - Previous research has established that patients suffering from anxiety disorders,
      including post-traumatic stress disorder (PTSD), exhibit a cognitive bias that
      selectively favours the processing of threat material. This information
      processing bias has frequently been demonstrated by subjects' performance on the
      Stroop colour-naming task. The current experiment investigated the selective
      processing of threat information in people with PTSD using a modified Stroop
      procedure. Subjects were 13 ferry disaster survivors with high PTSD
      symptomatology, 20 survivors of the same disaster with low PTSD symptomatology,
      and 12 non-traumatized control subjects. All were asked to colour-name five types
      of words: ferry disaster words, general threat words, neutral semantically
      unrelated words, neutral semantically-related words, and positive words. The
      disaster survivors with high levels of PTSD symptomatology evidenced a
      significantly longer response latency for colour-naming disaster-related words
      than for other word types. The results of the low-PTSD survivors and non
      traumatized controls showed no significant difference between response latencies
      for general threat words and disaster word, although all 3 groups showed
      increased latencies for threat words compared with neutral words. The mechanisms
      proposed to underlie this response pattern are discussed, and clinical
      implications are considered.

PMID- 8155065
TI  - Validity issues in self-statement measures of social phobia and social anxiety.
AB  - Measures to assess internal dialogue or self-statements in socially phobic or
      anxious clients are now frequently used in clinical and research settings. Such
      cognitive assessment techniques are rarely considered, however, with regard to
      psychometric criteria. This article reviews the literature on self-statement
      assessment of social phobia and social anxiety from the perspective of content,
      criterion, convergent and discriminant validity. In general, most measures have
      shown good evidence of validity. Different scoring systems in addition to thought
      valence appear worthwhile, and multiple measures and assessment occasions should
      be considered.

PMID- 8155066
TI  - Cognitive assessment strategies and the measurement of outcome of treatment for
      social phobia.
AB  - With the development of cognitive-behavioral theories and treatments for the
      emotional disorders, there is an increased need for the development and
      utilization of assessment devices to quantify cognitive constructs. This is
      especially important in the study and treatment of social phobia, an anxiety
      disorder that appears to have a significant cognitive component. In this paper, I
      review and evaluate the use of cognitive assessment strategies in studies of the
      cognitive-behavioral treatment of social phobia. Although much useful data have
      been collected, studies that included any form of cognitive assessment relied
      heavily on questionnaire assessment of fear of negative evaluation or irrational
      beliefs, with only occasional use of other methods such as thought listing or
      self-statement questionnaires. In the latter part of the review, I focus on the
      potential utility of other measures including those derived from the growing
      literature on the processing of information among persons with social phobia or
      other anxiety disorders. Studies that have demonstrated differences between
      social phobics and comparison groups are reviewed, and the potential uses of
      these information processing techniques are examined. The cognitive assessment of
      social phobia and its response to cognitive-behavioral interventions remains in
      its childhood, although the transition to adolescence may be on the horizon.

PMID- 8155067
TI  - Exposure to 60 Hz magnetic fields in the electric utility work environment.
AB  - Research that has attempted to examine the relationship between work exposures to
      magnetic fields and health effects has suffered from limited exposure
      information. Power-frequency electric and magnetic (EM) field exposures vary
      substantially between industries, occupations, and individuals. In this study
      magnetic field data were collected for a variety of occupational categories
      within an electric utility. The sampling procedures emphasized craft occupations
      that were presumed to have higher exposures to magnetic fields. The objectives
      were to provide better exposure information for an ongoing cancer mortality
      study, examine the relationship between different summary measures of magnetic
      field exposure, and make available descriptive information useful for exposure
      reduction and worker education. Principal components analysis (PCA) and Varimax
      rotation were used to explore the relationships between the different summary
      measures among all utility workers and among the subset of electrical craft
      occupations. Discriminant analysis was used to assess summary measures of
      exposure that differentiated occupational groups. Measurements for 770 days
      generated a total of 42378 hours of magnetic field data. Eleven summary indices
      of exposure were calculated for specific occupational groups. These include
      arithmetic mean, geometric mean, median, 95th and 99th percentiles, and fraction
      of measurements exceeding .5, 1, 5, 10, and 100 microT. Electrical craft
      occupations had higher work exposures than non-craft occupations. Electricians
      and substation operators had the highest exposures among craft occupations. We
      identified subsets of summary measures that were intercorrelated. The first PCA
      axis included the geometric mean, median, and the fractions exceeding 0.5 and 1.0
      microT. This set of measures also were best at discriminating occupational
      groups. The relevance of these findings may become more important if consistent
      associations are found between particular occupations and disease and particular
      occupations and magnetic field summary measures. Further research is needed to
      evaluate these exposure assessment findings.

PMID- 8155068
TI  - Development of a protocol for assessing time-weighted-average exposures of young
      children to power-frequency magnetic fields.
AB  - A study was carried out in 1990 to guide the development of a protocol for
      assessing residential exposures of children to time-weighted-average (TWA) power
      frequency magnetic fields. The principal goal of this dosimetry study was to
      determine whether area (i.e., spot and/or 24 h) measurements of power-frequency
      magnetic fields in the residences and in the schools and daycare centers of 29
      children (4 months through 8 years of age) could be used to predict their
      measured personal 24-h exposures. TWA personal exposures, measured with AMEX-3D
      meters worn by subjects, were approximately log-normally distributed with both
      residential and nonresidential geometric means of 0.10 microT (1.0 mG). Between
      subjects variability in residential personal exposure levels (geometric standard
      deviation of 2.4) was substantially greater than that observed for nonresidential
      personal exposure levels (1.4). The correlation between log-transformed
      residential and total personal exposure levels was 0.97. Time-weighted averages
      of the magnetic fields measured in children's bedrooms, family rooms, living
      rooms, and kitchens were highly correlated with residential personal exposure
      levels (r = 0.90). In general, magnetic field levels measured in schools and
      daycare centers attended by subjects were smaller and less variable than measured
      residential fields and were only weakly correlated with measured nonresidential
      personal exposures. The final measurement protocol, which will be used in a large
      US study examining the relationship between childhood leukemia and exposure to
      magnetic fields, contains the following elements: normal- and low-power spot
      magnetic field measurements in bedrooms occupied by subjects during the 5 years
      prior to the date of diagnosis for cases or the corresponding date for controls;
      spot measurements under normal and low power-usage conditions at the centers of
      the kitchen and the family room; 24-h magnetic-field recordings near subjects'
      beds; and wire coding using the Wertheimer-Leeper method.

PMID- 8155069
TI  - Acceptance speech on the occasion of receiving the d'Arsonval Medal.

PMID- 8155070
TI  - A model for characterizing residential ground current and magnetic field
      fluctuations.
AB  - The current through the residential grounding circuit is an important source for
      magnetic fields; field variations near the grounding circuit accurately track
      fluctuations in this ground current. In this paper, a model is presented which
      permits calculation of the range of these fluctuations. A discrete network model
      is used to simulate a local distribution system for a single street, and a
      statistical model to simulate unbalanced currents in the system. Simulations of
      three-house and ten-house networks show that random appliance operation leads to
      ground current fluctuations which can be quite large, on the order of 600%. This
      is consistent with measured fluctuations in an actual house.

PMID- 8155071
TI  - Sleep inducing effect of low energy emission therapy.
AB  - The sleep inducing effect of a 15 min treatment with either an active or an
      inactive Low Energy Emission Therapy (LEET) device emitting amplitude-modulated
      electromagnetic (EM) fields was investigated in a double-blind cross-over study
      performed on 52 healthy subjects. All subjects were exposed to both active and
      inactive LEET treatment sessions, with an interval of at least 1 week between the
      two sessions. LEET consists of 27.12 MHz amplitude-modulated (sine wave) EM
      fields emitted intrabuccally by means of an electrically conducting mouthpiece in
      direct contact with the oral mucosa. The estimated local peak SAR is less than 10
      W/kg in the oral mucosa and 0.1 to 100 mW/kg in brain tissue. No appreciable
      sensation is experienced during treatment, and subjects are therefore unable to
      tell whether they are receiving an active or an inactive treatment. In this study
      the active treatment consisted of EM fields intermittently amplitude-modulated
      (sine wave) at 42.7 Hz for 3 s followed by a pause of 1 s during which no EM
      fields were emitted. During the inactive treatment no EM fields were emitted.
      Baseline EEGs were obtained and 15 min post-treatment EEGs were recorded and
      analyzed according to the Loomis classification. A significant decrease (paired t
      test) in sleep latency to stage B2 (-1.78 +/- 5.57 min, P = 0.013), and an
      increase in the total duration of stage B2 (1.15 +/- 2.47 min, P = 0.0008) were
      observed on active treatment as compared with inactive treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155072
TI  - Magnetic fields after translation in Escherichia coli.
AB  - Quantitative two-dimensional gel electrophoresis of proteins in E. coli exposed
      for 60 min to weak, pulsed magnetic fields (1.5 mT peak) show that numerous
      proteins are both increased and decreased by a factor of 2 or more. An increase
      in the levels of two proteins, the a subunit of DNA-dependent RNA polymerase and
      NusA, was confirmed by Western blot analysis.

PMID- 8155073
TI  - Enhanced mutagenic effect of a 60 Hz time-varying magnetic field on numbers of
      azide-induced TA100 revertant colonies.
AB  - Forty-eight hours exposure to a two Gauss (0.2 mT) rms 60 Hz time varying
      sinusoidal electromagnetic field increased the number of azide induced TA100
      revertant colonies of Salmonella typhimurium 14% as compared with controls in the
      ambient < 2 milli-Gauss 60 Hz field. In the absence of the electromagnetic field,
      the numbers of mutant colonies grown within and outside the non-energized coil
      were nearly identical. Without azide, the number of "spontaneous" mutant colonies
      forming in the experimental field was not statistically significant from numbers
      of colonies not exposed to field effects. Experimental temperature variation of 2
      degrees C had little effect on colony formation, and the enhanced production of
      revertant colonies in the presence of the magnetic field was maintained during
      continued culture for 5 additional days.

PMID- 8155074
TI  - [ATP-dependent proteinase La from Escherichia coli].
AB  - Homogeneous preparations of the ATP-dependent La proteinase from E. coli and two
      its mutant forms, containing an alanine residue instead of Ser679 or Ser368, were
      isolated. Ser679 was shown to be catalytically active rather than Ser368 as
      suggested in the literature. To choose between the alternative structures of the
      gene lon La proteinase fragments within the controversial regions were analysed
      and the gene structure established at the Laboratory of Proteolytic Enzymes
      (Institute of Bioorganic Chemistry) was confirmed. Inactivity of La proteinase in
      some in vitro systems suggests its functioning in vivo to be not autonomous,
      requiring additional factors.

PMID- 8155075
TI  - [Effectiveness of proteolytic enzymes].
AB  - A theory of the ground state's destabilization is developed explaining the high
      efficiency of proteases. The theory suggests a participation of the valence
      interactions in the formation of a productive complex and connects the efficiency
      and the specificity of proteolysis with the structure of such a complex. Proved
      is nonproductivity of nonvalence complexes in which the reactive amide group of
      the substrate is planar. It is suggested that the theory of the absolute rates of
      reactions does not cover the process of the enzymatic hydrolysis.

PMID- 8155076
TI  - [Proteolytic enzymes in the regulation of biological processes].
AB  - The role of proteolytic enzymes in protein processing, receptor-mediated
      processes and intercellular interactions is reviewed. Limited proteolysis is
      suggested to be a mechanism through which the information stored in polypeptide
      chains and necessary for realization of particular biological functions could be
      most fully expressed.

PMID- 8155077
TI  - [Basic metalloproteinases of the connective tissue matrix].
AB  - Metalloproteinases play a key role in the destruction of connective tissue matrix
      both upon normal physiological processes associated with remodelling of
      connective tissue and in various pathological situations. Variability of the
      matrix metalloproteinases, their specificity, structural features, activity
      regulation in vitro and in vivo, as well as their role in processes of oncogenic
      transformation are reviewed.

PMID- 8155078
TI  - [Proteolytic enzyme inhibitors of protein nature].
AB  - New data on the mechanism of interaction between proteolytic enzymes and protein
      inhibitors are presented. Most of known serine proteinase inhibitors bind to
      proteolytic enzymes through a substrate-like mechanism. A different mechanism is
      observed in the case of the inhibition of thrombin by hirudin and of papain by
      cystatin (from egg white) and stephin B. Protopeptides released during activation
      of some proteinase zymogens may act as efficient enzyme inhibitors. Such zymogens
      can be considered as covalently bound enzyme-inhibitor complexes.

PMID- 8155079
TI  - [Structural organization of the streptokinase molecule].
AB  - Conformational changes of the tryptophan-containing sites of streptokinase, its
      secondary and tertiary structures under the effect of NaCl, urea, heating, pH
      solution shift were analysed. Data on the reversibility of streptokinase's
      conformational changes, the flexibility of its structure, the presence of domains
      in the molecule were considered.

PMID- 8155080
TI  - [Inhibition of esterase by L-lysine, the activator and fibrinolytic activity of
      the plasmin-streptokinase activator complex].
AB  - The effect of L-lysine on some reactions catalysed by plasmin and the plasmin
      streptokinase activator complex has been studied. The constants for competitive
      inhibition by L-lysine of the benzyloxycarbonyl-L-lysine p-nitrophenyl ester
      hydrolysis by the activator (Ki 116 mM), of the plasminogen activation by the
      activator (Ki 8 mM) and of fibrinolysis by plasmin (Ki 3 mM) were determined. It
      was found that L-lysine at concentrations below 0.05 M, which do not affect the
      activator's esterase activity, does inhibit fibrinolysis by plasmin and the
      activator complex. The effect of L-lysine on fibrinolysis under the action of the
      activator is complex: it inhibits both the activation of clot-entrapped
      plasminogen by the activator and lysis of fibrin by the plasmin formed. This
      inhibitory action of L-lysine is largely related to the fact that it lowers the
      sorption of the activator, plasminogen and plasmin on fibrin, competing with
      fibrin for their lysine-binding sites as well as worsens the activator
      plasminogen binding.

PMID- 8155081
TI  - [Hydrolysis of proteins by collagenolytic proteinases from the king crab].
AB  - Hydrolysis of collagen molecules in the presence of collagenolytic proteases A
      and C from the king crab has been studied by electrophoresis. Both proteases are
      shown to hydrolyze effectively type I and III collagens, patterns of the products
      differing for the proteases A and C. The thermal denaturation of the type I
      collagen increased the effectiveness of the enzymatic hydrolysis. The crab
      collagenolytic proteases catalyze the hydrolysis of such proteins as bovine serum
      albumin, ovalbumin, horse cytochrome c, mouse immunoglobulin G, casein and human
      fibrinogen, only elastin being resistant. The mechanisms of the fibrinogen
      cleavage differ not only for the proteases A and C but also for plasmin, whereas
      the efficiencies in all the cases are similar.

PMID- 8155082
TI  - [The chemistry of proteolysis].
AB  - Experimental data obtained in this laboratory led to the determination of the
      mechanism of hydrolysis of peptide bonds by proteolytic enzymes. Efficiency and
      specificity of proteinases are explained in terms of the substrate state in the
      productive enzyme-substrate complex. An advanced classification of proteinases
      based on their mechanism of action is suggested.

PMID- 8155083
TI  - Recent observations on the role of hemostatic determinants in the development of
      the atherothrombotic plaque.
AB  - Recent evidence suggests that hemostatic determinants play a major role in the
      evolution of the atherothrombotic plaque. Platelets can serve as cholesterol
      donors for macrophages, thereby facilitating foam cell formation. Lipoprotein(a)
      inhibits fibrinolysis and may also contribute to atherogenesis by serving as a
      ligand for the scavenger receptor. By complexing with fibrin(ogen) in
      atheromatous lesions, lipoprotein(a) attenuates clearance of this protein,
      promoting atherogenesis and vascular dysfunction. These observations suggest that
      thrombotic determinants are critical for the development of the atheromatous
      plaque, and may guide the appropriate selection of potential therapeutic options
      in the future.

PMID- 8155084
TI  - LDL-apheresis and concomitant ACE-inhibitor therapy.

PMID- 8155085
TI  - Enrichment with apolipoprotein E characterizes postprandial TG-rich lipoproteins
      in patients with non-insulin-dependent diabetes mellitus and coronary artery
      disease: a preliminary report.
AB  - An oral fat-load test was carried out in patients with non-insulin-dependent
      diabetes mellitus (NIDDM) and angiographically verified coronary artery disease
      (CAD; group 1, n = 6); in patients with CAD but no diabetes (group 2, n = 6); in
      patients with NIDDM but no CAD (group 3, n = 4); and in healthy control subjects
      (group 4, n = 4). Concentrations of apolipoprotein (apo) E, apo C-II,
      triglyceride (TG), retinyl palmitate, and cholesterol were measured in fasting
      plasma and in plasma obtained after 2, 4, 6, 9, and 24 h after a meal containing
      78 g of fat and 345,000 IU of vitamin A. The same measurements were carried out
      in the lipoprotein fractions with Svedberg flotation rates Sf 400-1100, 60-400,
      20-60 and 12-20, obtained by density gradient ultracentrifugation. The
      postprandial apo E concentrations were highest in group 1 (NIDDM and CAD) in
      plasma and in the TG-rich lipoprotein fractions, with significant differences in
      comparison with the healthy subjects. As shown by apo E to TG ratios, the
      postprandial lipoproteins were enriched with apo E in the patients with NIDDM and
      CAD. The largest excesses of apo E in group 1 patients were observed in the
      atherogenic Sf 12-60 lipoproteins. Across the entire study population, there was
      a significant inverse correlation between the postprandial apo E responses and
      the postheparin lipoprotein lipase activity. The results suggest that enrichment
      of the remnant lipoproteins with apo E may have a role in the increased risk of
      CAD among patients with NIDDM.

PMID- 8155086
TI  - Relationship between angiographically assessed coronary artery disease, plasma
      insulin levels and lipids in Asians and Caucasians.
AB  - In the present study the association between angiographically demonstrated
      coronary artery disease lipid subfractions and insulin in Caucasians, Asian
      migrants to the UK and Asians in India was studied. Patients having at least one
      angiographic lesion of more than 50% were recruited and angiograms scored by two
      independent observers, blindly. There were 87 Caucasian, 83 British Asian and 30
      Indian Asian patients. Lipid subfractions measured were cholesterol, HDL
      cholesterol, triglyceride, apo A1, apo B, Lp(a). Estimation of glucose and
      insulin was carried out at fasting and after two hours of oral 75 g glucose.
      Asians were younger than Caucasians. They did not differ in their body mass
      index, systolic and diastolic blood pressure or cigarette consumption. In all
      three ethnic groups cholesterol, LDL cholesterol and apo B showed significant
      positive association. Insulin levels at fasting or post glucose challenge failed
      to show any association. Apo B may be an additional marker for coronary artery
      disease in the ethnic groups studied.

PMID- 8155087
TI  - Reduced serum lipoprotein(a) levels in patients with primary biliary cirrhosis.
AB  - Lipoprotein(a) (Lp(a)) is a unique lipoprotein, elevated serum levels of which
      are independently associated with an increased risk of coronary heart disease
      (CHD). Primary biliary cirrhosis (PBC) is often associated with high serum
      cholesterol, itself a risk factor for CHD. Despite this, patients with PBC are
      thought to have a lower than expected incidence of CHD. We hypothesised that this
      may be related to low serum levels of Lp(a) in PBC patients. This was
      investigated by collecting fasting blood samples from 42 patients with PBC, 39
      age- and sex-matched subjects with non-PBC liver disease and 432 community
      control subjects. Serum was analysed for total cholesterol, triglycerides, high
      density lipoprotein (HDL) cholesterol and apolipoproteins A1 and B (apo A1 and
      apo B). Lp(a) was measured by an enzyme-linked immunosorbent assay (ELISA)
      technique. There was a significant reduction of Lp(a) concentrations in the PBC
      group compared with the healthy controls (median value 28.5 mg/l vs. 75.0 mg/l, P
      < 0.005) and between the non-PBC liver disease group (median value 52.0 mg/l) and
      control group (P = 0.001). Within both the liver disease and PBC patient groups
      there were significant negative correlations between Lp(a) levels and bilirubin
      (R = -0.564, P < 0.001 and R = -0.395, P = 0.010 respectively). This preliminary
      study has demonstrated reduced Lp(a) levels in PBC patients which may be a
      contributory factor to explain a possible cardioprotective effect in such
      patients, despite elevated LDL cholesterol levels.

PMID- 8155088
TI  - Short-term intra-individual variation and long-term tracking of serum lipid
      levels in children: the Cardiovascular Risk in Young Finns Study.
AB  - We have studied the short-term intra-individual variation and long-term tracking
      until early adulthood of serum total cholesterol, low density lipoprotein (LDL)
      cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride levels
      in 9-year-old Finnish boys. The study was based on two different cohorts; one to
      study short-term tracking and another to study long-term tracking. The short-term
      tracking cohort consisted of 57 healthy Finnish 9-year-old boys with serum lipid
      determinations 2 and 7 days apart in 1984. The other cohort consisted of 40
      healthy Finnish 9-year-old boys and the serum lipid determinations were made in 3
      year intervals from 1980 to 1989. Tracking was expressed as Spearman's rank order
      correlation coefficients between subsequent measurements. Tracking was weaker as
      the time between measurements became longer. For serum total cholesterol the
      correlation coefficients were 0.92, 0.77, 0.70, 0.73, and 0.59 for measurements
      made 2 days, 7 days, 3 years, 6 years, and 9 years apart, respectively. Other
      lipid variables behaved quantitatively in a similar manner. The dependence of
      tracking on time was not linear. The greatest relative decrease in correlations
      took place during the determination periods of 2 and 7 days, whereafter the
      decline was only moderate. In conclusion, short-term intra-individual variation
      of serum lipid levels in children, which is mainly due to biological variation,
      has a major influence on their long-term tracking. Our findings emphasize the
      need for several independent serum lipid determinations, performed at least one
      week apart, in the assessment of a child's true serum lipid level.

PMID- 8155089
TI  - Lipoprotein-proteoglycan complexes from injured rabbit aortas accelerate
      lipoprotein uptake by arterial smooth muscle cells.
AB  - Lipoprotein-proteoglycan (LP-PG) complexes are taken up more avidly by
      macrophages and smooth muscle cells (SMCs) than native lipoproteins (LPs). The
      enhanced uptake may contribute to lipid accumulation and foam cell formation
      during atherogenesis. Endothelial injury is known to alter proteoglycan (PG)
      synthesis and distribution in the neointima developed in response to injury. The
      present study examines the uptake and degradation of LP-PG complexes, derived
      from PG of injured aortas by arterial SMCs. Rabbit apo-B lipoprotein (LP),
      including VLDL, IDL and LDL was isolated by ultracentrifugation and coupled with
      PG extracted from normal aortas (NPG) or with PG from injured aortas (IPG).
      Rabbit aortic SMCs were cultured from intima-media explants, incubated with 125I
      LP, 125I-LP-NPG or 125I-LP-IPG for 20 h at 37 degrees C. LP binding,
      internalization and degradation were markedly increased (P < 0.001) for LP-NPG
      and LP-IPG over native LP. Competition experiments indicated that more than 50%
      of the LP-PG complexes were taken up by the apo-B/E receptor pathway.
      Phagocytosis was the second important route of uptake of these complexes, whereas
      the scavenger receptor played a minor part in the uptake and degradation of LP-PG
      complexes. Data from this study indicate that LP-PG complexes accelerate LP
      uptake and degradation by SMC more than native LP. Therefore, these complexes may
      contribute to lipid accumulation by SMC, thus generating foam cells. Furthermore,
      LP-PG complexes prepared from PG of injured aortas are more effective in lipid
      accumulation than LP-PG complexes from PG of normal aortas.

PMID- 8155090
TI  - Apolipoprotein E and B polymorphisms--longevity factors assessed in
      nonagenarians.
AB  - To test if the prevalence of genetic risk factors for coronary heart disease
      (CHD) is low in individuals who have reached an extremely old age, the allele
      frequencies of apolipoprotein E (apo E) and B (apo B) polymorphisms and plasma
      lipoprotein(a) levels were investigated in nonagenarians and in younger control
      groups. The frequency of the epsilon 4 allele of apo E was significantly lower in
      the nonagenarians than in the middle-aged and young adults (P < 0.05). Also, the
      frequency of EcoRI allele R- of apo B was low in the nonagenarians, whereas the
      allele frequency for the XbaI polymorphism of apo B and plasma lipoprotein(a)
      concentrations did not differ between the nonagenarians and the younger groups.
      These findings strongly suggest that the presence of these potential genetic risk
      factors for CHD, namely the epsilon 4 allele of apo E and the R- allele of apo B,
      decreases the probability of an individual reaching an extremely old age.

PMID- 8155091
TI  - Long-term effects of three fat-modified diets in hypercholesterolemic subjects.
AB  - Altogether 160 free living subjects (aged 30-60 years) most of whom had moderate
      hypercholesterolemia were randomised into the following diet groups to find out
      long-term effects of different fat-modified diets: (1) control diet 35/14:10:4
      (energy percents from fat/saturated:monounsaturated:polyunsaturated fatty acids
      in actual diets); (2) AHA type diet 32/10:8:8; (3) monoene-enriched diet
      34/11:11:5; (4) reduced-fat diet 30/12:8:3. LDL cholesterol fell equally with the
      AHA type diet (4.54 +/- 0.97 vs. 4.21 +/- 0.89 mmol/l (mean +/- S.D., 0 vs. 6
      months), P = 0.001) and with the monoene-enriched diet (4.55 +/- 0.95 vs. 4.25 +/
      0.95 mmol/l, P = 0.004) during the 6-month study. Moderate amounts of polyenes
      or monoenes as part of natural diets did not decrease HDL cholesterol level in
      the long term. Serum lipid values remained unchanged with the reduced-fat diet.
      Analysis by apolipoprotein E phenotypes showed a decrease in LDL cholesterol only
      in subjects with phenotype 3/3 in the monoene-enriched group (-8.6 +/- 8.7 vs.
      +1.3 +/- 15.4, percent change in LDL cholesterol E 3/3 vs. E 4/3 + 4/4), but in
      the AHA type group LDL cholesterol decreased similarly in phenotypes E 3/3 and E
      4/3 + 4/4 (-6.9 +/- 10.1 vs -6.9 +/- 16.5).

PMID- 8155092
TI  - Ultrastructure and permeability of endothelial cells in branched regions of rat
      arteries.
AB  - The ultrastructure and the permeability to macromolecules of the endothelia in
      the branched and unbranched regions of the arteries were compared using two
      different age groups (3 and 12 months) of rats. In the aortic arch, the
      endothelial cells were longer and thinner and contained fewer intracytoplasmic
      vesicles than those observed in the unbranched regions of aorta. Quantitative
      study revealed that the volume density of intracytoplasmic vesicles in the
      branched regions of aortic arch in 3-month-old rats was significantly (P < 0.01)
      lower than the density value in the unbranched regions of aorta. The volume
      densities of vesicles in both regions of the aorta were lower than those in the
      carotid artery. There was an apparent increase in the frequency of the simple
      type of interendothelial contacts and a decrease in the complex type in the
      branched regions as compared with those in the unbranched regions of aorta and
      carotid artery. In addition to the normal interendothelial contacts, several open
      junctions with increasing width (25-300 nm) were identified in the branched
      regions of aortic arch and the bifurcations of carotid artery. For rats at the
      age of 12 months, local areas of the subendothelial space were expanded. Basal
      lamina-like and electron-dense materials were accumulated in the subendothelium.
      The volume densities of vesicles in the aortic endothelia were significantly (P <
      0.01) increased as compared with those in the 3-month-old group. The volume
      density of vesicles in the aortic arch was again significantly (P < 0.01) lower
      than that in the unbranched regions of aorta. Furthermore, the frequency of the
      simple type of intercellular contacts was increased, whereas that of the complex
      type was decreased in both regions of aorta. With regard to the junctional
      complexes, the frequencies of gap junctions and tight junctions were increased
      and the junctionless intercellular contacts were decreased compared with those of
      the 3-month-old group.

PMID- 8155093
TI  - We may be lost, but we're sure makin' good time.

PMID- 8155094
TI  - Hypertension following primary bladder closure for vesical exstrophy.
AB  - Since the initiation of staged reconstruction for bladder exstrophy, hypertension
      has been a known complication of the procedure. The etiology of the elevation in
      blood pressure was presumably secondary to ureteral dysfunction caused by edema
      at the ureterovesical junction and secondary renal obstruction. This report
      details the clinical course of three patients who developed significant
      hypertension following primary bladder closure with posterior iliac osteotomies
      and bony immobilization by skin traction. None of the patients had urinary
      obstruction and all had their hypertension alleviated by removal of the traction.
      The presumed etiology of the elevated blood pressure within these patients is
      similar to that experimentally produce by inappropriately applied traction
      resulting in tension on the sciatic nerve and reflex induced vasoconstriction.
      The need to maintain appropriately applied traction and the necessity of
      monitoring the postoperative blood pressure is stressed.

PMID- 8155095
TI  - Breast cancer and pregnancy: a review.

PMID- 8155096
TI  - Langerhans' cell histiocytosis and malignancies of the M-PIRE system.

PMID- 8155097
TI  - Is atypical odontalgia a psychological problem?
AB  - Several authors have asserted that psychological factors are the underlying cause
      of atypical odontalgia. However, objective evidence is lacking to support this
      claim. In this study, the Minnesota Multiphasic Personality Inventory was used to
      assess psychological functioning of an atypical odontalgia population. Means of
      the standard scores for each Minnesota Multiphasic Personality Inventory scale
      were within normal ranges. Standard scores for atypical odontalgia profiles
      compared with standard scores for a chronic headache group (matched for age, sex,
      and chronicity) were similar and scales for both groups were within normal
      ranges. These findings fail to support psychological dysfunction as a primary
      condition associated with patients suffering from atypical odontalgia.

PMID- 8155098
TI  - Birthweight curves in southern Israel populations.
AB  - With the aim of establishing a standard range of birthweights at different
      gestational ages for Jewish and Bedouin populations, we analyzed 5.5 years of
      computerized delivery files. Strictly confirmed gestational age was required in
      this study. This is necessary for proper diagnosis of growth abnormalities, such
      as growth retardation and macrosomia, for research purposes and for assessment of
      perinatal morbidity and mortality at a given gestational age. Percentile
      distributions of birthweights of 46,529 infants are presented. The mean
      birthweight of male infants was 3,238 g (SD 529 g) and of female infants was
      3,117 g (SD 504 g). From week 36 to week 41 of gestation, infants of Jewish
      mothers were significantly heavier than infants born to Bedouin women,
      particularly in primiparous women. In both Jewish and Bedouin births, male
      infants were significantly heavier than female infants after the 36th week of
      gestation, by 130 g in the former and 127 g in the latter. Although the set of
      birthweight percentile curves of Jews and Bedouins was similar to the Colorado
      birthweight curve, some differences were found. At 41 and 42 weeks of pregnancy
      our infants were heavier and exceeded the standard, whereas at weeks 35 to 38 the
      standard exceeded the median weight of the Bedouin infants. The differences
      between our population curves and the commonly used Colorado standard curve
      emphasize the need for locally based and periodically updated infant birthweight
      data.

PMID- 8155099
TI  - New translocation involving homologous chromosome 3 in acute myelogenous leukemia
      (M2)
AB  - An apparent balanced translocation involving the long arms of homologous
      chromosomes is described for the first time in a patient with acute myelogenous
      leukemia (AML) (M2), i.e., 46,XY,t(3;3) (q21;q26). After reviewing the
      literature, it was noted that a breakpoint involving band 3q26 is a frequent
      anomaly in other translocations. Thus, we are tempted to hypothesize that 3q26
      band may also play an important role in the pathogenesis of AML (M2).

PMID- 8155100
TI  - Segmental neurofibromatosis clinically appearing as a nevus spilus.

PMID- 8155101
TI  - Mandatory national health service. An idea whose time has come.

PMID- 8155102
TI  - Empowerment: on eagle's wings.

PMID- 8155103
TI  - Severe hypophosphataemia in a patient with acute leukaemia.

PMID- 8155104
TI  - Clinical management of concussion.
AB  - Concussion is an injury that occurs frequently in the general community. Most
      cases are caused by sporting accidents, falls and assaults. This article reviews
      the presentation and management of this common problem. High velocity impacts as
      in motor vehicle accidents may result in concussion but are more likely to
      produce a serious brain injury.

PMID- 8155105
TI  - Hormone replacement therapy and breast cancer.

PMID- 8155106
TI  - A low male/female sex ratio in offspring of women with a family history of pre
      eclampsia and eclampsia.

PMID- 8155107
TI  - Gene transfer therapy in cancer.
AB  - Gene transfer techniques have now achieved clinical realization in the wake of
      recent advances in recombinant DNA technology, together with increased
      understanding of the molecular biology and immunology of cancer. These novel
      treatments, and their applications and limitations merit intensive study.

PMID- 8155108
TI  - Towards safer endoscopic retrograde cholangiopancreatography.

PMID- 8155109
TI  - Friction amyloidosis: a variant or an etiologic factor in amyloidosis cutis?
AB  - BACKGROUND: During a study of cutaneous amyloidosis, it was noticed that a
      significant number of patients gave a history of friction of some kind or other,
      which when analyzed could be clearly related to their cutaneous pigmentation. A
      common feature in all these patients was the relative lack of itching when
      compared with others who did not give a history of friction. METHODS: We studied
      the role of friction in 65 patients with amyloidosis cutis and found that in 20
      patients, frictional factors could be attributed to their cutaneous condition,
      and these latter were taken up for further study. RESULTS: Histologic examination
      of the affected area of skin showed amyloid deposits, which could be detected by
      light microscopy with hematoxylin and eosin stained sections and confirmed by
      special stains. CONCLUSIONS: The role of friction in the causation of lesions
      that resemble amyloidosis cutis morphologically is discussed.

PMID- 8155110
TI  - Dietary strategies for cancer prevention.
AB  - BACKGROUND: Two-thirds of cancer cases are associated with two lifestyle
      practices: 35% with the typical American diet, and 30% with tobacco use. In
      contrast to the field of tobacco control, research and resources dedicated to the
      field of nutrition have been limited, in part because dietary change has been
      considered controversial and requires a more complex set of interventions.
      METHODS: This series of papers reviews the science base underlying diet as a
      cancer control strategy, including research about diet-cancer relationships,
      current nutrition policy recommendations, American dietary trends, models of
      dietary behavior change, and diet in health care delivery. The history of
      technology transfer of new knowledge into widespread application will be compared
      and contrasted with other cancer control measures. RESULTS: There is scientific
      and policy agreement about three priority dietary goals for the year 2000:
      increase fruit and vegetable consumption to 5 or more servings every day,
      increase breads, cereals, and legumes to 6 or more servings daily, and decrease
      fat to no more than 30% of total calories. Current data do not indicate that
      these goals will be reached. As yet there is no organized effort, with clearly
      identified steps, to translate research into practice. The parallel with delays
      in implementing other cancer control measures, including Papanicolaou testing,
      mammography, and tobacco intervention, is striking. CONCLUSION: Without resources
      dedicated to dietary modification in the general population, it is not likely
      that the potential savings of more than 300,000 new cases, 160,000 deaths, and
      the $25 billion in associated costs will be realized in the foreseeable future.

PMID- 8155111
TI  - Angio-oedema with droperidol.

PMID- 8155112
TI  - Orotracheal intubation in patients with potential cervical spine injuries. An
      indication for the gum elastic bougie.
AB  - The conditions for emergency tracheal intubation of patients with cervical spine
      injury were simulated in 157 patients during induction of anaesthesia for routine
      surgery. The view of the larynx obtained during laryngoscopy with the head in the
      optimum intubating position was compared with that obtained when manual in-line
      stabilisation of the cervical spine and cricoid pressure were used. During
      laryngoscopy with cervical stabilisation, the view of the larynx was reduced in
      45% of patients, and in 22% of patients nothing was visible beyond the
      epiglottis. To assess the ease of intubation with the neck stabilised and with
      cricoid pressure applied, patients were randomised to either direct visual
      intubation (n = 79), or intubation aided by a gum elastic bougie (n = 78). The
      median time taken for visual intubation was 20 s, but in six patients intubation
      took over 45 s. In addition, five patients in this group could not be directly
      intubated. Using the gum elastic bougie all patients, including the failures from
      the visual group, were intubated within 45 s (median 25 s). We recommend the gum
      elastic bougie as an aid to intubating the patient with suspected cervical spine
      injury, particularly when the glottis is not immediately visible.

PMID- 8155113
TI  - Intravenously administered immune globulin for the treatment of infection
      associated hemophagocytic syndrome.
AB  - Infection-associated hemophagocytic syndrome is an unusual disease with a high
      mortality rate. A variety of treatment modalities have been used with limited
      success. We report three patients with infection-associated hemophagocytic
      syndrome successfully treated with intravenously administered immune globulin.

PMID- 8155114
TI  - Skin cryosurgery for the family physician.
AB  - Cryosurgery is a valuable addition to the clinical services offered by family
      physicians. In the office setting, a cryoprobe cooled with nitrous oxide gas or
      liquid nitrogen spray can be used to initiate gradual controlled destruction of
      many common skin lesions. Cryosurgery is often an excellent alternative to cold
      knife surgery for actinic and seborrheic keratoses, verrucae, benign nevi, skin
      tags and polyps. Cryosurgically treated lesions usually heal with little or no
      scar formation. The benefits of various cryosurgical techniques justify the
      minimal effort and expense required to incorporate them into clinical practice.

PMID- 8155115
TI  - Randomized trial of laser scalpel for modified radical mastectomy.
AB  - The efficacy of a contact neodymium yttrium-aluminium-garnet laser scalpel was
      assessed during breast surgery. Forty consecutive women undergoing modified
      radical mastectomy were randomized to operation performed with a conventional or
      laser scalpel. The laser scalpel was associated with a significant reduction in
      mean operative blood loss (149 versus 421 ml; 95 per cent confidence interval of
      difference 176-368 ml, P < 0.001), but the mean operating time was longer (105
      versus 80 min; 95 per cent confidence interval of difference 16-34 min, P <
      0.001). No significant differences were found in the volume of postoperative
      wound drainage, incidence of axillary seroma, postoperative pain score or time to
      return of shoulder mobility. Use of a laser scalpel in breast surgery cannot be
      recommended.

PMID- 8155116
TI  - Oral medicine/diagnostic radiology/clinical oral pathology.

PMID- 8155117
TI  - Specimen-orientated radiography helps define excision margins of malignant
      lesions detected by breast screening.
AB  - Eighty patients with impalpable breast lesions detected by mammographic screening
      underwent hookwire-guided wide local excision. Excision specimens were orientated
      with Ligaclips and submitted to radiography; if, on the specimen radiograph, the
      mammographic lesion crossed any visible margin, further tissue was excised. Clear
      histological margins were obtained on the initial excision in 52 (68 per cent) of
      77 carcinomas. After inspection of the orientated specimen radiograph, further
      tissue was excised from 22 patients; this significantly increased the rate of
      complete excision to 86 per cent (P < 0.01). Significantly more patients with
      invasive cancer had a complete excision than those with ductal carcinoma in situ
      (52 of 57 versus 14 of 20, P < 0.02).

PMID- 8155118
TI  - Late discharge of stones after laparoscopic cholecystectomy.

PMID- 8155119
TI  - Cancer of the ovary.

PMID- 8155120
TI  - Endometrial ablation and air embolism.

PMID- 8155121
TI  - "Putting back the bugs": bacterial treatment relieves chronic constipation and
      symptoms of irritable bowel syndrome.

PMID- 8155122
TI  - Hypercholesterolaemia: not all cases warrant treatment.

PMID- 8155123
TI  - Tea tree oil poisoning.

PMID- 8155124
TI  - Deaths associated with dentistry.

PMID- 8155125
TI  - Combined high frequency ventilation.

PMID- 8155126
TI  - Antenatal assessment of neurological impairment.

PMID- 8155127
TI  - Surgery for luxating patella in a calf.

PMID- 8155128
TI  - Rising beta-hCG titres following laparoscopic injection of methotrexate into
      unruptured, viable tubal pregnancies.

PMID- 8155129
TI  - A randomized trial of 45 minute and 15 minute incremental oxytocin infusion
      regimes for the induction of labour in women of high parity.

PMID- 8155130
TI  - Drug treatment of hypercholesterolaemia. Review criteria for cholesterol tests.

PMID- 8155131
TI  - Deciding who should have thrombolysis.

PMID- 8155132
TI  - Alzheimer's disease and Lewy body dementia.

PMID- 8155133
TI  - Alzheimer's disease and Lewy body dementia.

PMID- 8155134
TI  - Measurement of subcutaneous glucose concentration.

PMID- 8155135
TI  - Adreno-cortical reserve in pulmonary tuberculosis.

PMID- 8155136
TI  - Invited letter concerning: balloon dilation of stenotic aortic valve in children-
      an intraoperative study (J Thorac Cardiovasc Surg 1992; 104:1709-13)

PMID- 8155137
TI  - Invited letter concerning: nonpulsatile flow--a noncontroversy.

PMID- 8155138
TI  - The limits of federal power: a question of liberty.

PMID- 8155139
TI  - Lipoid proteinosis or infantile systemic hyalinosis?

PMID- 8155140
TI  - Hypophosphataemia and leukaemia.

PMID- 8155141
TI  - Why is acute preoperative plasmapheresis not uniformly effective at decreasing
      bleeding following cardiac surgery?

PMID- 8155142
TI  - Towards safer endoscopic retrograde cholangiopancreatography (ERCP)

PMID- 8155143
TI  - Reduction of manpower: a solution to the problem of busyness.

PMID- 8155144
TI  - Chronobiological studies on pain threshold.

PMID- 8155145
TI  - Alternative methods for the control of sheep scab.
AB  - For nearly 17 years, plunge dipping has been the only method of scab control in
      the UK under a Government-controlled eradication campaign. Dipping is
      inconvenient and has been incriminated in the post-dipping illness of stockowners
      and contractors, and the disposal of large volumes of used dipwash is a potential
      hazard to the environment. Upon the deregulation of sheep scab in July 1992,
      stockowners are no longer obliged to dip and will seek alternative methods of
      scab control, ie, systemic injectables or synthetic pyrethroid pour-ons. Plunge
      dipping still offers the only fully effective method of controlling scab and it
      has a broad spectrum of activity against other ectoparasites of sheep. The
      present systemic pour-ons and oral drenches have little effect against scab, but
      double injections of systemic acaricides, ie, ivermectin, show great promise. The
      efficacy of systemic injectables is related to the initial mite burden and the
      second injection must not be omitted if complete control is to be achieved. The
      available synthetic pyrethroid pour-ons do not cover the entire sheep with a
      standard dose of acaricide, and leave the ventral surfaces unprotected and the
      sheep open to reinfestation.

PMID- 8155146
TI  - Methods of applying liquid nitrogen for skin surgery.

PMID- 8155147
TI  - Cardiorespiratory arrest and combined spinal/epidural anaesthesia for caesarean
      section.

PMID- 8155148
TI  - Management of asthma in general practice. Question about occupation and hobbies.

PMID- 8155149
TI  - Management of trauma.

PMID- 8155150
TI  - Concurrent infection with hepatitis B and C viruses.

PMID- 8155151
TI  - Treatment of malignant melanoma.

PMID- 8155152
TI  - Late discharge of stones after laparoscopic cholecystectomy.

PMID- 8155153
TI  - Abstinence or controlled drinking?

PMID- 8155154
TI  - Abstinence or controlled drinking?

PMID- 8155155
TI  - CT before lumbar puncture.

PMID- 8155156
TI  - In response to Dr. Arthur Koffler's article.

PMID- 8155157
TI  - Questions about the honesty French nephrologists.

PMID- 8155158
TI  - Friction amyloidosis.

PMID- 8155159
TI  - Fixation of vascularized bone grafts.

PMID- 8155160
TI  - HLA and classic Kaposi's sarcoma in Sardinia.

PMID- 8155161
TI  - Participation of physicians in capital punishment.

PMID- 8155162
TI  - Participation of physicians in capital punishment.

PMID- 8155163
TI  - Graduate education in physiological optics.

PMID- 8155164
TI  - Developing survival skills.

PMID- 8155165
TI  - Death scene gas analysis in suspected methane asphyxia.

PMID- 8155166
TI  - Corporal punishment.

PMID- 8155167
TI  - Guidelines for the evaluation of impairment/disability in patients with asthma.

PMID- 8155168
TI  - Endothelin-1 in persistent pulmonary hypertension of the neonate.

PMID- 8155169
TI  - Furuncular myiasis: alternatives to Bacon therapy.

PMID- 8155170
TI  - Regulation of water balance between blood and lymph in the frog, Rana pipiens.

PMID- 8155171
TI  - Cancer of the ovary.

PMID- 8155173
TI  - Cardiac pacemakers.

PMID- 8155172
TI  - Tobacco-specific lung carcinogen and exposure to passive smoking.

PMID- 8155174
TI  - Averting disaster in the management of the patient with a mediastinal mass.

PMID- 8155175
TI  - Postdural puncture headache.

PMID- 8155176
TI  - The laryngeal mask and patients with 'collapsible' airways.

PMID- 8155177
TI  - Leucovorin versus folic acid in the treatment of methotrexate toxicity: comment
      on the article by Shiroky et al.

PMID- 8155178
TI  - Elevation of cardiac output and oxygen delivery improves outcome in septic shock.

PMID- 8155179
TI  - Mandatory national health service.

PMID- 8155180
TI  - Mandatory national health service.

PMID- 8155181
TI  - The cost of Marinol (dronabinol)

PMID- 8155182
TI  - Folate supplements should be appropriately labeled to protect consumers.

PMID- 8155183
TI  - The rectus abdominis flap for exposed vascular grafts of the lower extremity.

PMID- 8155184
TI  - Glass ampules--another approach.

PMID- 8155185
TI  - Carbon dioxide and sperm motility.

PMID- 8155186
TI  - [Gestational trophoblastic diseases].

PMID- 8155187
TI  - [Trophoblastic diseases. Traps in the histologic diagnosis].

PMID- 8155188
TI  - [Tuberculosis. Role of fine needle puncture in the current diagnostic approach].
AB  - Twenty-one fine needle aspiration biopsies were performed with a diagnosis of
      tuberculosis or granulomatous inflammation. The ages of the patients ranged from
      26 to 66 years (mean, 36 years); 16 were men and 5 women. Two of them were
      positive for the human immunodeficiency virus. In twenty cases, the cytological
      diagnosis was confirmed by culture and/or by recovery under a specific anti
      tuberculous treatment. In one case, the necrosis observed cytologically was a
      tumoral necrosis after histological control. According to these results with a
      global accuracy of 95.2%, fine needle aspiration biopsy which offers the
      possibility of a thorough diagnosis in a short time (24 hours or less) is a
      useful method for the diagnosis of tuberculosis.

PMID- 8155189
TI  - [Lymphatic metastasis revealing a calcitonin-secreting extrathyroid carcinoma].
AB  - We report a case of right sus-clavicular lymph nodes metastasis which revealed a
      calcitonin secreting carcinoma in a 36 years old woman. Any tumor has been noted
      in the completely included thyroid gland. There was many lymph nodes metastasis
      in the right mediastinal removal. A pulmonary origin neuroendocrine carcinoma
      hyposthesis has been evoked. The outcome proved to be quickly fatal with cerebral
      metastasis occurrence. Extrathyroid calcitonin secreting carcinomas are rare.
      Then the discussion was founded on the diagnosis process in the face of
      hypercalcitoninemia, and on the calcitonin secretion by neuroendocrine cells and
      neoplasms of the lung.

PMID- 8155190
TI  - [Splenoma with accumulation of megakaryocytes during the course of an idiopathic
      myelofibrosis].
AB  - We report a splenoma associated with an important megakaryocyte sequestration in
      peliotic sinuses. The diagnosis was done on surgical specimen of splenectomy
      performed for a painful splenomegaly occurring in a 71-year-old man presenting a
      primary idiopathic myelofibrosis. Histopathological features of these splenic
      microvascularization disorders, mainly occurring during hemopathy involving the
      spleen, are discussed. This case seems to confirm the hypothesis that splenoma
      could be an acquired splenic disease.

PMID- 8155191
TI  - [Lympho-epithelial lesions induced by plasma cells in a pulmonary MALT lymphoma].
AB  - One case of pulmonary lymphoma of MALT origin is reported. The diagnosis was made
      by histological and immunohistological study of surgical specimen. Cytologically,
      the tumoral proliferation was made by an admixture of centrocyte-like cells,
      small lymphocytes and vacuolized plasma cells. Lympho-epithelial lesions were
      particular because induced by tumoral plasma cells. From this case, problems of
      diagnosis and physiopathology of pulmonary MALT lymphomas are discussed.

PMID- 8155192
TI  - [Ectopic deposits of Tamm-Horsfall protein. A psuedo-tumoral lesion].
AB  - Three cases of unusual deposits of Tamm-Horsfall protein in peripelvic and
      perirenal fat tissue are reported. A renal tubular rupture leads to the
      deposition of this protein. In the first case, the association of the deposits
      with epithelial structures, raised the possibility of a bladder carcinoma
      infiltration. These deposits simulated on the X-ray examination, a pelvis
      neoplasm in our second patient and a tuberculosis in the third case. However the
      particular microscopic appearance of Tamm-Horsfall protein, its intense staining
      with the periodic-acid-Schiff, and its positivity with a specific antibody led to
      the diagnosis.

PMID- 8155193
TI  - [A cyst may be hidden by another. Cutaneous cysticercosis].

PMID- 8155194
TI  - [Cutaneous tumor in a patient with POEMS syndrome].

PMID- 8155195
TI  - [A hunting story...massive intra-ocular ossification following injury].

PMID- 8155196
TI  - [A breast nodule to follow. Lymphocytic mastopathy or lymphocytic and fibrous
      lobi mammae].

PMID- 8155197
TI  - [Primary colorectal linitis plastica manifested as an occlusive syndrome].

PMID- 8155198
TI  - [Classification of odontogenic tumors, 2nd edition (WHO, 1992)].

PMID- 8155199
TI  - [From mitochondrial myopathy to mitochondrial cytopathy].

PMID- 8155200
TI  - Postpartum myocardial infarction in a patient with antiphospholipid syndrome.
AB  - Myocardial infarction in association with pregnancy in patients with the
      antiphospholipid syndrome has been reported once previously. Our patient, a 22
      year-old multiparous woman, experienced a myocardial infarction in the postpartum
      period. She fulfilled the criteria for the diagnosis of the antiphospholipid
      syndrome (elevated anticardiolipin antibody levels, false-positive syphilis
      serology, history of deep vein thrombosis). Cardiac catheterization demonstrated
      appropriate central filling pressures, cardiac output of 7.14 L/min, and normal
      appearing coronary arteries. She was treated with corticosteroids and
      indomethacin and recovered. Our article is relevant to clinical practice for the
      following reasons. First, it is the second time myocardial necrosis has been
      reported in a recently pregnant woman with the antiphospholipid syndrome. Second,
      the finding of normal-appearing coronary arteries at the time of catheterization
      lends credence to the hypothesis that either vasospasm or thrombosis are the
      inciting events. We speculate on the utility of various treatment regimens.

PMID- 8155201
TI  - Ultrasound placental cysts associated with massive placental stem villous
      hydrops, diploid DNA content, and exomphalos.
AB  - A pregnancy associated with antenatally detected placental cysts and an anterior
      abdominal wall defect is described. The anterior abdominal wall defect proved to
      be an exomphalos in which a short segment of normal cord intervened between the
      herniated sac and the cord insertion. The placental cysts detected antenatally by
      ultrasound were shown subsequently to be massive main stem villous hydrops with
      cisternal formation but no evidence of trophoblastic hyperplasia. Antenatal
      placental biopsy and amniocentesis revealed a normal male karyotype. Confined
      placental mosaicism for triploidy was excluded by DNA flow cytometry. This case
      was not associated with Beckwith-Wiedemann syndrome.

PMID- 8155202
TI  - Trisomy 21 and cystic hygromas in early gestational age fetuses.
AB  - Chromosomal aberrations are associated with 60% of cystic hygromas and the
      majority of these are females with a 45,X karyotype. Trisomy 21 has rarely been
      reported. Six cases of cystic hygromas with trisomy 21 were detected during a 6
      month time period in our laboratory. An earlier gestational age of 14 weeks was
      present in our cases compared with a gestational age of 18 weeks reported in the
      literature. Because of the high rate of fetal loss prior to 16 weeks, many cases
      of trisomy 21 with cystic hygromas may go undetected. This suggests that cystic
      hygromas detected before 16 weeks of gestation may be clinically different from
      those detected later in gestation. With the increasing use of chorionic villus
      sampling and amniocentesis at 10 to 12 weeks of gestation, trisomy 21 may be a
      common finding in fetuses with cystic hygromas.

PMID- 8155203
TI  - Color Doppler imaging of the thyroid gland in a fetus with congenital goiter: a
      case report.
AB  - Fetal goiter is a rare disorder, usually associated with maternal thyroid
      disease. Antenatal diagnosis of fetal goiter is crucial for the immediate
      postpartum management of these neonates. A case report is presented of an
      antenatally diagnosed fetal goiter induced by antithyroid medications. Color
      Doppler was used to demonstrate a high flow pattern that, unlike in the adult
      goiter, was associated with hypothyroidism in the neonate. A scan of fetal neck
      region is recommended in patients with current or previous history of thyroid
      disease, or if neck extension is noted on routine examination of fetal spine.

PMID- 8155204
TI  - Endometritis after cesarean: the effect of age.
AB  - In this study, we compared the rate of endometritis after cesarean section in two
      age groups. The first group consisted of patients who were 17 years old or
      younger (teenage group) and the second group of patients were 35 years of age or
      older (advanced maternal age group). Patients in each group were matched for
      length of labor, length of rupture of membranes, and the use of prophylactic
      antibiotics. In the teenage group, 18 of 41 (43.9%) developed endometritis
      compared with 6 of 41 (14.6%) in the advanced maternal age group (P < 0.003).
      This study supports the concept that young age is a risk factor for endometritis
      after cesarean section.

PMID- 8155205
TI  - Coagulation studies in very low-birthweight infants.
AB  - Reference values for coagulation studies of premature infants (24 to 29 weeks'
      gestational age) are needed for the management of hemostatic disorders in the
      precariously ill infant. We collected data on the very low-birthweight infants
      admitted to our intensive care nursery who met criteria over a 4-year period to
      determine prothrombin time, activated partial thromboplastin time, and fibrinogen
      levels in this group. Fifty-two infants had a mean prothrombin time of 14.5
      seconds, a mean activated partial thromboplastin time of 69.5 seconds, and a mean
      fibrinogen level of 1.35 g/L. Converting values to ratios of adult control values
      facilitated direct comparison of results to published reference ranges.
      Coagulation studies may vary over a broad range of prematurity, and normal ranges
      are needed for prospective, randomized protocols designed to prevent the
      complications of abnormal coagulation function.

PMID- 8155206
TI  - Necrotizing enterocolitis and hypothyroidism in a newborn infant: treatment with
      intravenous L-thyroxine.
AB  - Gastrointestinal complications of hypothyroidism are well documented and include
      constipation, obstipation, and abdominal distention, as well as ileus, pseudo
      obstruction, tumor-like mass of the intestine, and megacolon. We report herein on
      a 2-week-old, full-term female infant, who had both necrotizing enterocolitis
      (NEC) and congenital hypothyroidism. We further describe the response to therapy
      with intravenous L-thyroxine. To our knowledge, the patient's course is the first
      report of intravenous L-thyroxine in the management of congenital hypothyroidism
      when oral replacement is not an option. The possible causal relationship between
      NEC and hypothyroidism is discussed.

PMID- 8155207
TI  - Differential leukocyte count in babies treated with natural surfactant.
AB  - The potential of exogenous replacement therapy in surfactant-deficient states
      such as neonatal respiratory distress syndrome (RDS) is an area of intense
      clinical interest today. At present, a fundamental problem with any type of
      exogenous surfactant is the uncertainty about potential effects on physiological
      defense mechanisms, such as differentiation and mobilization of peripheral
      leukocytes. Considering that newborn infants with proven bacterial infections
      have abnormal values of segmented (neutrophil) and nonsegmented (band)
      polymorphonuclear leukocytes, we studied 42 placebo- versus Curosurf-treated
      babies with severe RDS. Differential white blood cell (WBC) count was serially
      performed before and after treatment during the first days of life. The
      statistically significant increase in the proportion of bands in surfactant
      treated babies did not coincide with clinical and bacteriologic evidence of
      possible infection. Some molecular interaction mechanisms influencing immature to
      mature WBC ratio are supposed. Among a variety of influences on the leukocyte
      count, surfactant replacement therapy needs to be considered for proper
      interpretation of hematologic data in babies treated for RDS.

PMID- 8155208
TI  - Posterior urethral valves in successive generations.
AB  - Posterior urethral valves (PUV) are a frequent cause of urinary tract obstruction
      in infant males and may be diagnosed by antenatal ultrasound. PUV have been
      observed in siblings and in identical twins. However, genetic factors in PUV are
      poorly understood. In this article, we report the occurrence of PUV diagnosed
      antenatally in a fetus whose father and paternal uncle were both treated for PUV
      in childhood. This is the first reported case of PUV that we are aware of
      occurring in successive generations.

PMID- 8155209
TI  - Value of maternal fructosamine in the screening of an unselected population for
      hyperglycemia-related complications in the newborn.
AB  - The relationship between the maternal serum fructosamine concentration and
      pregnancy outcome was studied in 765 consecutive subjects of an obstetric
      community hospital population. The neonatal outcome of patients with a
      fructosamine concentration in pregnancy below and above 2.30 mmol/L were
      compared. Patients with a fructosamine concentration above 2.30 mmol/L did not
      show an increased incidence of neonatal hypoglycemia, hyperbilirubinemia, or
      respiratory distress syndrome. On the other hand, they did give birth to infants
      with a higher birthweight ratio, a variable defined as newborn weight corrected
      for sex, gestational age, and parity. However, the predictive value with respect
      to birthweight ratio was modest: Fructosamine accounted for only 1.4% of the
      variation in birthweight ratio, much less than other well-known contributors to
      this variation, such as smoking (10%) and prepregnancy maternal (6.5%) or
      paternal weight (2.8%). The screening value of fructosamine to identify patients
      who would give birth to a macrosomic infant was limited irrespective the
      gestational age at measurement. It is concluded that fructosamine determined
      during pregnancy in an unselected obstetric population is an unsuitable screening
      method to trace patients with an increased risk to deliver of an infant with
      neonatal complications of maternal hyperglycemia.

PMID- 8155210
TI  - Gentamicin levels in pregnant women with pyelonephritis.
AB  - This study was performed at University Medical Center, Lubbock, Texas, from July
      1989 to June 1990. We obtained serum gentamicin peak and trough levels in 23
      pregnant women with pyelonephritis. The patients were given a loading dose of 2
      mg/kg gentamicin, followed by 1.5 mg/kg gentamicin adjusted for obesity every 8
      hours. Peak levels were obtained 1 hour after the fifth dose and trough levels
      were drawn 30 minutes before the sixth dose. Statistical analysis was performed
      using chi 2 analysis. The mean (+/- SD) peak gentamicin level was 2.7 +/- 1.4
      micrograms/mL and the mean trough level was 0.5 +/- 0.3 micrograms/mL. Twenty-two
      of 23 (96%) patients had peak levels 5 micrograms/mL and 1 of 23 (4%) patients
      had peak levels between 5 and 10 micrograms/mL. The mean peak gentamicin level in
      pregnancy is significantly less than in puerperal women (2.70 versus 5.78; P <
      0.000001). We conclude that the majority of pregnant women treated for
      pyelonephritis with standard doses of gentamicin do not achieve therapeutic
      levels. Also, peak gentamicin levels are significantly below that reported for
      puerperal women.

PMID- 8155211
TI  - Accurate intrapartum estimation of fetal platelet count by fetal scalp samples
      smear.
AB  - Fetal scalp sampling has been used to determine fetal platelet count in early
      labor. Because platelet clumping may lead to falsely low platelet counts, this
      pilot study was carried out to evaluate an improved method of scanning an
      intrapartum fetal scalp smear for platelet estimation. We report 5 years'
      experience with the use of scanning of the smear for platelet aggregates instead
      of direct measurement of platelets. In 22 cases, intrapartum examination of the
      scalp blood smear at low power revealed the great majority of high-power, dry
      microscopic fields devoid of platelets, whereas isolated fields contained
      aggregates of more than 10 platelets. In one case, an adequate number of
      platelets were evenly distributed. Intrapartum fetal platelet estimation by
      scanning of the smear (using these platelet aggregates) correctly identified an
      adequate neonatal platelet count in 23 cases (mean, 264,600 +/- 15,000; range,
      133,000 to 396,000). Cesarean section was avoided in 82.6% of these cases. In
      this pilot study, platelet estimation on fetal scalp sample were reliably
      performed by scanning of the smear for platelet aggregates. When aggregates were
      seen, platelet adequacy was found in all cases.

PMID- 8155212
TI  - Value of the fern test to confirm or reject the diagnosis of ruptured membranes
      is modest in nonlaboring women presenting with nonspecific vaginal fluid loss.
AB  - The strength of the fern test to differentiate between amniotic and nonamniotic
      fluid in vaginal discharge was determined in 51 term women in labor with ruptured
      membranes and compared with that in a group of 120 nonlaboring subjects,
      presenting with nonspecific vaginal fluid loss. Sensitivity and specificity in
      the laboring group were 98.0 and 88.2%, respectively, in agreement with previous
      reports. In contrast, in the non-laboring group sensitivity and specificity were
      only 51.4 and 70.8%, respectively. The result of the fern test predicted the
      actual state of the membranes correctly in 63% and incorrectly in 29% of these
      patients. In 16 or 39 subjects with ruptured membranes (approximately 40%), the
      outcome of the fern test was negative. The modest diagnostic strength of the fern
      test in the present study compared with previously reported data is at least in
      part due to differences in study population (laboring versus nonlaboring) and to
      the fact that observers were deprived of relevant clinical information. It is
      concluded that the fern test should be granted supportive rather than conclusive
      value in diagnosing ruptured membranes in nonlaboring women presenting with
      nonspecific vaginal fluid loss.

PMID- 8155213
TI  - Maternal hyperglycemia is not the only cause of macrosomia: lessons learned from
      the nonobese diabetic mouse.
AB  - Maternal hyperglycemia has been implicated as the major cause of neonatal
      macrosomia, yet clinicians frequently report the birth of large-for-gestational
      age infants in normoglycemic pregnancies. We examined the relationship between
      birthweight, maternal blood glucose (BG), glycosylated hemoglobin (GHb) levels,
      litter size, maternal age, gestational duration, and parity using the non-obese
      diabetic (NOD) mouse model. We observed 133 litters and analyzed the birthweight
      in relation to BG, GHb, litter size, maternal age, gestational duration, and
      parity. We found that mean litter birthweight was significantly negatively
      correlated with the total number of pups in each litter (r = -0.39; P < 0.01) and
      significantly positively correlated with parity (r = 0.19; P < 0.05) and maternal
      age (r = 0.22; P < 0.05). The total number of pups was significantly negatively
      correlated with parity (r = -0.33; P < 0.01) and with parent age (r = -0.21; P <
      0.05). The relationship between birthweight and GHb was bimodal. No relationship
      was found with a GHb less than 2.5%, a significant positive correlation was found
      for GHb between 2.6% and 4.0% (r = 0.67; P < 0.01), and a negative relationship
      was found when GHb was above 4.0%. Thus, increased parity, maternal age and
      glucose are associated with increased birthweight. Mild hyperglycemia plays the
      major role when age, maternal size, gestational duration, and parity are
      controlled.

PMID- 8155214
TI  - Evaluation of the possibilities for preventing congenital toxoplasmosis.
AB  - Little is known about the best way to prevent congenital toxoplasmosis. Until
      recently, the major effort was directed at preventing the disease during
      pregnancy by the application of hygienic measures (primary prevention). With the
      advent of detecting congenital toxoplasmosis antenatally, another method for
      reducing the incidence of congenital toxoplasmosis becomes possible (secondary
      prevention). In this study, we evaluate these two methods for the prevention of
      congenital toxoplasmosis. For 12 consecutive years, we studied the incidence of
      congenital toxoplasmosis in 11,286 consecutive pregnant women. The impact of
      primary prevention was studied by measuring the reduction in seroconversion when
      hygienic measures were systematically applied. Primary prevention reduces the
      seroconversion rate during pregnancy by 63% (P = 0.013). The effect of secondary
      prevention was studied in 76 pregnant women at risk of delivering a child with
      congenital toxoplasmosis. Secondary prevention by means of serological screening
      combined with prenatal diagnosis detected congenital toxoplasmosis correctly in
      eight infected fetuses. Secondary prevention reduced the incidence of congenital
      toxoplasmosis an additional 40%. This reduction would predominantly be seen in
      the group of mildly to severely affected fetuses. From this study, the
      effectiveness of primary prevention is obvious. Health education on how to avoid
      toxoplasmosis during pregnancy should become standard obstetric care. Adequate
      serological screening and prenatal diagnosis can be helpful in reducing further
      the incidence of congenital toxoplasmosis. Whether or not screening for
      toxoplasmosis during pregnancy should be combined with primary prevention depends
      on the importance of congenital toxoplasmosis as a health problem in a given
      geographic area.

PMID- 8155215
TI  - Pneumoretroperitoneum and perirenal air associated with tension pneumothorax.
AB  - I report a case of a low-birthweight infant delivered by cesarean section because
      of maternal preeclampsia and breech presentation. The infant developed
      pneumoretroperitoneum and perirenal air associated with tension pneumothorax.

PMID- 8155216
TI  - Recurrent Bandl's ring as an etiology for failed vaginal birth after cesarean
      section.
AB  - A pathologic retraction ring (Bandl's ring) of the uterus is a constriction
      located at the junction of the thinned lower uterine segment and the thick
      retracted upper uterine segment that is associated with obstructed labor. The
      following is the first reported case of recurrent pathologic retraction ring and
      an attempted vaginal birth after cesarean section following such an abnormality.

PMID- 8155217
TI  - Umbilical venous catheterizations: audit by the Study Group for Complications of
      Perinatal Care.
AB  - The Study Group for Complications of Perinatal Care, through 13 of its
      participating neonatal intensive care units, conducted a prospective audit to
      describe contemporary use of umbilical venous catheters (UVCs) over 3 months in
      1951 admissions. Frequency of UVC attempts was 15.5% for all patients and
      greatest (50%) in patients of 1000 g or less birthweight (BW), with a wide range
      of frequency by institution and by BW grouping. Institutions with more 1500 g or
      less BW infants tended to use UVCs more frequently. The most common reason for
      placement was general intravascular access. A variety of fluids were infused, and
      in most cases heparin was employed. Mean duration of use was 4.4 days for all
      patients and longest (5.5 days) in infants in the 1001 to 1500 g BW group. The
      most common reason for UVC removal was lack of further need. UVCs appear to be
      used more commonly and for a longer duration than is currently recommended. There
      is a need for a prospective, randomized trial to assess the risks properly and
      maximize the benefits of UVC usage.

PMID- 8155218
TI  - Infant formula distribution and advertising in pregnancy: a hospital survey.
AB  - A survey was conducted at a 526-bed community hospital in Rochester, New York, to
      determine the prevalence of formula advertising and distribution during pregnancy
      to 136 consecutive intrapartum patients. Women answered a questionnaire about
      their choice of infant feeding methods and prenatal exposure to formula
      advertising. Of those who received printed information on infant feeding, 78
      percent reported that it was published by a formula company, and 65 percent
      recalled receiving offers for free formula during their pregnancy. The likelihood
      of having received such offers was the same in women who planned to breastfeed as
      in those who planned to formula feed. Thirty-eight percent of women obtained
      formula through a free offer before their infant's birth. Women who were
      privately cared for were more likely to have received offers for free formula (p
      < 0.001) than were women cared for in hospital-affiliated clinics. Ninety percent
      of women who received free formula prenatally reported their prenatal caregiver
      as a source of samples. Of samples that women obtained prenatally, 93 percent
      were from companies that advertise only indirectly through hospitals and
      physicians, whereas 7 percent were from companies that advertise directly to
      patients. The prevalence of formula company advertising during the prenatal care
      of women who deliver in this hospital is high. The continued participation of
      prenatal caregivers in promotion efforts of formula companies provides a negative
      or mixed message about the importance of breastfeeding and may be a barrier to
      its success.

PMID- 8155219
TI  - Using research plus community action to change maternal health policy.

PMID- 8155220
TI  - Prevention of perineal trauma by perineal massage during pregnancy: a pilot
      study.
AB  - Although the performance of perineal massage by a woman or her partner during the
      last weeks of pregnancy may help to prevent perineal trauma at delivery, the
      technique has never been evaluated rigorously. This study examined the
      feasibility of a randomized, controlled trial, and more specifically assessed the
      participation rate, the acceptability of the intervention, and whether or not an
      attending physician could remain blind to participants' groups. The pilot study
      was a single-blinded, randomized, controlled trial. Nulliparous women, 32 to 34
      weeks pregnant, were recruited from June 8 to July 31, 1992, at the offices of
      family physicians and obstetricians who practice at the Hopital du Saint
      Sacrement in Quebec City. Women assigned to the intervention group practiced
      daily 10-minute perineal massage and completed a diary, and those in the control
      group had standard care. Women and attending physicians completed a questionnaire
      about the aspect of blindness. Among the 174 women who delivered during the study
      period, 104 (59.8%) were approached by a midwife and 46 (26.4%) were randomized.
      Twenty (91.0%) of the 22 women in the massage group returned their perineal
      massage diaries. Based on the postpartum questionnaire, 20 women practiced the
      technique at least four times a week for three weeks or longer. No woman in the
      control group practiced massage. The attending physician was aware of the woman's
      group in only three instances (6.7%). Based on the results of this pilot study, a
      randomized, controlled trial to evaluate the efficacy of perineal massage in
      preventing perineal trauma at birth appears feasible.

PMID- 8155221
TI  - Self-esteem, social support, and satisfaction differences in women with adequate
      and inadequate prenatal care.
AB  - This descriptive, retrospective study examined levels of self-esteem, social
      support, and satisfaction with prenatal care in 193 low-risk postpartal women who
      obtained adequate and inadequate care. The participants were drawn from a
      regional medical center and university teaching hospital in New Mexico. A
      demographic questionnaire, the Coopersmith self-esteem inventory, the personal
      resource questionnaire part 2, and the prenatal care satisfaction inventory were
      used for data collection. Significant differences were found in the level of
      education, income, insurance, and ethnicity between women who received adequate
      prenatal care and those who received inadequate care. Women who were likely to
      seek either adequate or inadequate prenatal care were those whose total family
      income was $10,000 to $19,999 per year and high school graduates. Statistically
      significant differences were found in self-esteem, social support, and
      satisfaction between the two groups of women. Strategies to enhance self-esteem
      and social support have to be developed to reach women at risk for receiving
      inadequate prenatal care.

PMID- 8155222
TI  - The cesarean section rate in Sweden: the end of the rise.
AB  - This nationwide study examined the annual changes in cesarean section rates in
      relation to perinatal mortality, the condition of the newborn at birth, and
      different indications for the procedure in Sweden. Since 1973 all obstetric units
      have sent copies of medical birth registration forms for newborns to the National
      Board of Health and Welfare. Information about the cesarean section rate,
      indications for the surgery, Apgar scores, and perinatal mortality between 1973
      and 1990 was obtained from this data base. The cesarean section rate increased
      from 5 percent in 1973 to 12.3 percent in 1983, and thereafter declined steadily
      to 10.84 percent in 1990. Perinatal mortality was halved from 14.2 to 6.3 per
      1000 live births, and the number of newborns with low Apgar scores (< 4 at 1 min
      and/or < 7 at 5 min) decreased from 20 to 14 per 1000 live births. We conclude
      that it is possible to lower the cesarean section rate on a nationwide basis
      without increasing risks to newborn infants.

PMID- 8155223
TI  - The Mother-Infant unit at Tallinn Children's Hospital, Estonia: a truly baby
      friendly unit.
AB  - A mother-infant neonatal unit was established in 1979 at Tallinn Children's
      Hospital in Estonia to provide medical and nursing care to newborn and premature
      babies and their mothers. Its leading principles are 24-hour care by the mother,
      minimal use of technology, and little contact between the baby and medical and
      nursing staff. The unit was based on a conceptual model of the "psychological and
      biological umbilicus," which proposes that this connection binds the mother and
      infant together during the early weeks of life. Separation of mother and baby
      disrupts this important tie and may have adverse consequences for both. This
      paper presents data comparing weight gain during the first 30 days of life for a
      group of 159 preterm and full-term infants who were admitted to the unit between
      1988 and 1989. Eighty-seven infants were cared for by their mothers, and 72 by
      nurses because their mothers were unwilling or unable to stay with the infants in
      the hospital. The holistic, humanistic approach used in the unit represents a
      truly baby-friendly hospital.

PMID- 8155225
TI  - Letter from England: home birth--a call for action.

PMID- 8155224
TI  - Satisfaction with care in labor and birth: a survey of 790 Australian women.
AB  - Data on satisfaction with care in labor and birth were gathered in a survey
      conducted in conjunction with a review of maternity services in Victoria,
      Australia. All women who gave birth in one week in 1989 (> 1000) were mailed
      questionnaires eight to nine months after the birth, with a response rate of 790
      (71.4%). When adjusted for parity in a logistic regression model, the following
      factors were highly related to dissatisfaction with intrapartum care: lack of
      involvement in decision making (p < 0.001), insufficient information (p < 0.001),
      a higher score for obstetric intervention (p = 0.015), and perception that
      caregivers were unhelpful (p = 0.04). No association was found between
      satisfaction and maternal age, marital status, total family income, country of
      birth, or health insurance status. The survey results were influential in shaping
      final recommendations of the Ministerial Review of Birthing Services by
      countering stereotypes about women who become dissatisfied with their care,
      providing evidence of far greater dissatisfaction with intrapartum than antenatal
      care, and demonstrating the importance of information, participation in decision
      making, and relationships with caregivers to women's overall satisfaction with
      intrapartum care.

PMID- 8155226
TI  - Comments on the AAMC policy statement recommending strategies for increasing the
      production of generalist physicians.
AB  - The United States has a physician specialty imbalance, primarily a shortage of
      generalists (defined as family physicians, general internists, and general
      pediatricians) relative to other specialists. In recent years, the rising costs
      of health care, the expansion of managed care, and problems of access to care
      have accentuated the critical role that generalists must play in a cost
      effective, accessible health care system. Despite numerous public and private
      initiatives designed to address the supply of generalist physicians, the ratio of
      generalists to specialists has been decreasing. Although the factors contributing
      to the shrinking proportion of generalists are many and are often outside the
      control of educators, there is evidence that medical schools can play a major
      role in influencing specialty choice. Recognizing the need to address the
      specialty imbalance in this country, the Association of American Medical Colleges
      (AAMC) appointed the Generalist Physician Task Force to develop a statement
      suggesting actions that the AAMC and its constituents could take to foster a
      greater representation of generalist physicians in the United States. The task
      force produced an Executive Summary, published as an AAMC policy statement in
      early 1993, that contained recommended strategies for medical schools, graduate
      medical education, and the practice environment. The authors of the present
      article critique these recommendations, provide a background and rationale for
      each of them, and give suggestions about how some of the recommendations might be
      implemented. While they are in general agreement with the AAMC policy statement,
      they feel the recommended strategies fall short of the need. They maintain that
      the AAMC statement represents an admirable but cautious approach to a daunting
      problem, and that the time is past when cautious approaches will suffice. The
      authors conclude with the hope that bolder initiatives will emerge from the new
      AAMC Office of Generalist Physician Programs.

PMID- 8155227
TI  - Retraining the subspecialist for a primary care career: four possible pathways.
AB  - The degree to which a reformed U.S. health care system relies on an adequate
      supply of primary care physicians will determine the urgency of change in the
      composition of the medical workforce. In many areas of the United States, the
      demand for primary care physicians, particularly in managed care settings, far
      exceeds the supply. In contrast, reports of reduced practice opportunities for
      medical and surgical subspecialists in the same settings are increasing. As
      opportunities for and incomes of primary care physicians are enhanced, some
      medical subspecialists may seek retraining in primary care. This article provides
      a context for understanding the development of physician retraining programs,
      examines precedents for retraining physicians, describes four possible pathways
      through which medical subspecialists might acquire primary care training, and
      emphasizes the importance of defining the scope of practice and necessary skills
      for providing primary care. Obstacles to retraining appear to be economic (Who
      will pay? Is the cost worth the benefit?) and jurisdictional (Who will define
      core competencies? Who will credential programs and trainees?). The current
      absence of demand for such retraining programs suggests either that marketplace
      induced changes will not take place or that the notion of a primary care provider
      shortage and an oversupply of medical subspecialists is overstated. The inclusion
      of physician retraining programs in proposed health reform legislation suggests
      that policymakers are convinced that such programs offer one viable solution to
      the nation's medical workforce needs.

PMID- 8155228
TI  - Faculty development through formal mentoring.

PMID- 8155229
TI  - Academic networks: mosaic and world wide web.

PMID- 8155230
TI  - Women's health and medical school curricula.

PMID- 8155231
TI  - Medical education and the generalist quest.

PMID- 8155232
TI  - The Clinical Skills Assessment Alliance.

PMID- 8155233
TI  - PBL and generalist careers.

PMID- 8155234
TI  - The USMLE and clinical competence.

PMID- 8155235
TI  - Experiential training in medication compliance for residents.

PMID- 8155236
TI  - Information sheet for patients in a teaching hospital.

PMID- 8155237
TI  - Learning, experience, and self-assessment of competence of third-year medical
      students in performing bedside procedures.
AB  - BACKGROUND: Third-year medical students are expected to perform common bedside
      procedures as part of their daily ward activities, but there are few programs to
      teach these skills or document students' abilities to perform them. PURPOSE: In
      addition to describing the clinical procedures course at the Medical College of
      Georgia School of Medicine, the purpose of this paper is to report how often
      students perform common bedside procedures during the third year of medical
      school, whether the number of times a procedure has been performed is indicative
      of self-perceived level of competence, and how useful the students find the
      procedures course for learning how to perform common procedures. METHOD: In June
      1991, the 163 entering third-year students participated in a two-day course in
      which they were taught universal precautions and provided specific step-by-step
      instructions for performing 16 clinical procedures. One year later, after the
      students had completed their third-year clerkships, they were asked to report the
      numbers of times they had performed the procedures during their clerkships, to
      provide self-assessments of their competency, and to indicate how helpful the
      course had been for learning clinical procedures. The association between the
      number of times the students reported performing a procedure and how competent
      they felt to perform the procedure was assessed using Kendall's tau coefficient.
      RESULTS: A total of 100 students returned completed questionnaires. Most of the
      students reported performing venipuncture, obtaining blood cultures, and
      scrubbing surgically more than five times, but they reported performing other
      procedures less frequently. For most procedures, self-assessment of competency
      correlated with frequency of performance. The procedures course was well received
      by students and instructors, based on both written evaluations and informal
      verbal feedback. CONCLUSION: Surprisingly, the students' self-reports indicated
      that many students performed procedures on patients infrequently. As expected,
      for most procedures there was a significant association between frequency of
      performance and self-assessed competency.

PMID- 8155238
TI  - Assessment of basic physical examination skills of internal medicine residents.
AB  - BACKGROUND: Internal medicine faculty at the Mayo Clinic designed a clinical
      evaluation exercise that separates assessment of physical examination skills from
      that of medical interviewing and reasoning skills. This report summarizes the
      first year's experience with assessment of basic physical examination skills.
      METHOD: A core faculty of five general internists and three internist
      subspecialists designed a 45-item general examination checklist (e.g., measure
      blood pressure, examine mouth, palpate liver, drape to ensure privacy). In
      addition, the core faculty generated a menu of 27 focused examination skills
      (e.g., examine for carpal tunnel syndrome) from which the faculty examiner would
      select five items for the resident to perform. Each checklist item was scored 0,
      1, or 2 for a maximum possible score of 100. The core faculty selected a
      criterion-based scoring reference and established a passing score of 90 based on
      practice examinations with residents and faculty. The core faculty made an
      instructional videotape of a model examination that was available to all
      residents. In 1991-92, prior to examination, the checklist was distributed to all
      first-year categorical (43), preliminary (25), and newly appointed second-year
      residents (eight). RESULTS: Of the 76 residents examined, 11 (14%) failed and 65
      (86%) passed. All failing scores were 86 or lower. The absence of scores 87, 88,
      and 89 suggested that faculty upgraded borderline performances. All 11 residents
      who initially failed retook the examination and passed. The five most commonly
      missed items were (1) inspect the skin, (2) complete examination in logical
      sequence, (3) palpate aorta, (4) auscultate anterior breath sounds, and (5)
      palpate axillary and inguinal nodes. Other important observed errors were failure
      to measure vital signs, confusion of liver and spleen, failure to use bell on
      stethoscope, and inadequate breast examination. Twenty-eight residents completed
      an optional feedback form. Reviews were mixed but generally favorable.
      CONCLUSION: Assessment of the basic physical examination skills of the internal
      medicine residents was useful, and such skills were able to be assessed
      separately from physical diagnosis skills and interviewing skills. Direct
      observation of basic physical examination skills revealed important deficiencies,
      which provided opportunity for remediation.

PMID- 8155239
TI  - Comparing peer and faculty evaluations in an internal medicine residency.
AB  - PURPOSE: To compare in-training evaluations of residents by their peers with
      evaluations by faculty preceptors in an internal medicine residency. METHOD: The
      study group consisted of 22 residents enrolled in the core (three-year) internal
      medicine program at the University of Calgary in 1989-90 and 1990-91. At the end
      of each rotation, ratings of the residents were requested from faculty preceptors
      and from peers for several categories of clinical competence. The peer ratings
      were paired with faculty ratings, for a total of 74 pairs of ratings. The
      Wilcoxon matched-pair signed-rank procedure was used to compare the paired
      ratings. One-way analysis of variance was used to compare the peer and faculty
      ratings with the residents' scores on three other kinds of evaluation used by the
      residency. RESULTS: While there was no significant difference between peer and
      faculty ratings for overall competence or for several components of competence,
      there were significant differences for some components, with faculty tending to
      rate higher than peers. The latter components were physical examination, team
      relationships, industriousness and enthusiasm, teaching, physician-patient
      relationships, and case presentations. External validation of the ratings by
      comparing them with other kinds of evaluation yielded little meaningful
      information. CONCLUSION: That the faculty ratings were significantly higher than
      the peer ratings for some components of clinical competence suggests that there
      were differences in the quality of evaluation between the peers and faculty, or
      differences in the standards or expectations of the two groups.

PMID- 8155240
TI  - Methods of recruiting and selecting residents for U.S. family practice
      residencies.
AB  - PURPOSE: To describe the strategies used by family practice program directors to
      recruit and select residents. METHOD: The residency directors of all 361 U.S.
      accredited nonmilitary family practice programs in 1992-93 were asked to complete
      three-page questionnaires regarding program descriptors, curriculum, benefits
      offered, interview process, and factors affecting their selection of residents.
      Each program was categorized into one of nine geographic regions. Variation of
      program characteristics across the regions was assessed using chi-square.
      RESULTS: A total of 282 directors (78%) returned usable questionnaires. The
      programs did not differ in benefits offered except that (1) those with low fill
      rates in the 1992 Match of the National Resident Matching Program were more
      likely to have additional financial incentives and (2) the programs in areas of
      high competition went to extra effort and expense to market their residencies
      through the use of advertising materials (e.g., pens, mugs). The most important
      factor in selecting applicants was listed as the personal interview by 51% of the
      directors and performance on clinical rotations by 36%. CONCLUSION: The residency
      directors' selection decisions were highly influenced by candidates' performances
      in interviews and on clinical rotations. The programs in the most competitive
      areas were characterized by greater efforts and increased expenditures of
      resources for recruiting. More research is needed to assess the values of the
      different strategies used by programs to recruit and select residents.

PMID- 8155241
TI  - Entering first-year medical students' attitudes toward managed care.
AB  - PURPOSE: To study the attitudes of entering first-year medical students toward
      reform of the U.S. health care system. METHOD: All 631 first-year medical
      students at the five medical schools in the University of California System were
      asked during orientation (late summer of 1992) to complete a self-administered
      questionnaire regarding their attitudes toward and knowledge about health care
      reform. Statistical methods used were chi-square tests and factor analyses.
      RESULTS: Of the 631 students, 594 (94%) responded. Of the respondents, 392 (66%)
      felt that there should be a national health insurance plan, and 428 (72%) felt
      that practicing physicians had a major responsibility to help reduce health care
      costs. When asked about specific changes intended to control health care costs,
      the students identified reform of the medical malpractice system (374, 63%) and
      increased spending on preventive health (356, 60%) as the most likely to be
      effective. The students generally held negative attitudes toward managed care
      organizations; only 59 (10%) indicated they would choose to receive care in
      health maintenance organizations. CONCLUSION: The students held strong opinions
      about access to care, managed care organizations, and strategies intended to
      reduce health care spending. Medical educators not only need to find creative
      methods of introducing these content areas into medical school curricula but
      should also anticipate the need for strategies to deal with negative attitudes
      held by students.

PMID- 8155242
TI  - Pilot-testing a holistic approach to scoring performance on standardized-patient
      examinations.
AB  - BACKGROUND: Scoring protocols for most standardized-patient (SP) examinations
      have not received extensive scrutiny and their validity has not been well
      established. METHOD: A holistic method (i.e., one based on raters' overall
      impressions) of scoring performance on an SP examination was pilot-tested in the
      spring of 1992 by administering an examination to two cohorts of fourth-year
      students at the Albert Einstein College of Medicine at Yeshiva University. The
      examination consisted of eight SP stations, representing a range of medical
      problems. Two to three experienced clinical teachers independently reviewed all
      the written material for each encounter. In Phase I of the study, holistic
      ratings of outstanding, competent, marginal, or inadequate were given for overall
      clinical competence for a cohort of 16 students; in Phase II, holistic ratings
      were given separately for data-gathering and communication skills for a cohort of
      26 students. Intercase and interrater reliability analyses were performed.
      RESULTS: Adequate reliability coefficients were obtained on a two-hour test;
      total scores (i.e., students' scores across all eight cases) discriminated
      between groups of examinees; and, on average, less than two minutes were required
      to score an encounter. CONCLUSION: Although based on a small sample, the study's
      results suggest that this holistic method of scoring performance may be useful in
      some situations. Since experienced clinical teachers know and agree about
      clinical competence when they see it, developers of scoring protocols for SP
      examinations need to establish that the results obtained are congruent with the
      judgments of expert teachers.

PMID- 8155243
TI  - Professionalism and clinical excellence among anesthesiology residents.
AB  - BACKGROUND: During a decade of evaluating the clinical performances of
      anesthesiology residents at several hospitals, a consistently low frequency of
      faculty members' comments regarding residents' unprofessional behavior was
      observed. METHOD: To identify the population of residents who behave
      unprofessionally and the predictive categories and performance patterns
      associated with unprofessional behavior, an examination was undertaken of 24
      months of clinical performance records regarding the behaviors of 71 residents
      for 15 negative categories and overall performance. The residents were in
      training from 1982-83 through 1989-90 at the University Hospitals of Cleveland.
      The performance records consisted of narrative comments from faculty that were
      converted into z-scores. These performance scores were evaluated by using
      percentage distributions, stepwise regression, and neural networks. RESULTS: Of
      the 71 residents, 15 (21%) received comments about unprofessional behavior, for a
      total of 27 comments (1% of all negative comments). Primarily, the residents'
      unprofessional behaviors involved unacceptable behavior (33%), abdication of
      responsibility (38%), and frank fabrications (15%). The 15 residents experienced
      significant problems in the areas of eagerness to learn, conscientiousness,
      composure, critical incidents, efficiency/organization, taking instruction, and
      knowledge. Problems with unprofessional behavior were not found for the 21
      residents whose scores for overall performance were excellent. CONCLUSION: The
      results expose a pattern of performance associated with unprofessional behavior,
      and suggest that clinical excellence and unprofessional behavior rarely coexist.

PMID- 8155244
TI  - Correlation of ratings of students' overall performance in a medicine clerkship
      with ratings of knowledge.

PMID- 8155245
TI  - Promoting medical students' appreciation of the nurse's role in labor and
      delivery.

PMID- 8155246
TI  - Perceptions of graduating medical students from problem-based and lecture-based
      curricula.

PMID- 8155247
TI  - Introduction: the never ending love for natural antibodies.

PMID- 8155248
TI  - The SCID mouse as a model for autoimmunity.

PMID- 8155249
TI  - Normal polyspecific immunoglobulin G (IVIg) in the treatment of autoimmune
      diseases.
AB  - Infusion of intravenous immunoglobulin (IVIg) has resulted in clinical
      improvement and/or a fall in autoantibody in a number of autoimmune and
      inflammatory diseases. Several lines of evidence demonstrate that IVIg may react
      with disease-associated autoantibodies through idiotypic interactions. In
      addition, infusion of IVIg results in changes in the expressed autoantibody
      repertoire that are dependent on interactions between variable regions of infused
      IgG and autoantibodies and in the subsequent alterations in the regulatory
      function of immune networks. Thus, pooled normal immunoglobulin restored in a
      patient with autoimmune thyroiditis the dynamics of spontaneous fluctuations of
      serum autoantibodies characteristic of physiological conditions. The ability of
      IVIg to interact with V regions of autoantibodies and with surface molecules of
      lymphocytes in vitro provides a basis for the selective modulation of B-cell
      clones observed in patients treated with immunoglobulins. The natural intrinsic
      complexity of IVIg provides a physiological rationale for immunoregulatory
      therapy of autoimmune disease.

PMID- 8155250
TI  - Elimination of infectious antigens and increase of IgG catabolism as possible
      modes of action of IVIg.
AB  - Many mechanisms can explain the mode of action of IVIg in immune disorders.
      Macrophage blockade and interference in the idiotypic network are supported by
      some experimental data. Among the other mechanisms, two are considered in greater
      detail. Firstly, in some disorders, the patients could improve simply because the
      infused Ig contains antibodies directed against the infectious antigen causing
      the disease. Secondly, one can expect that IVIg increases the IgG catabolism and
      therefore the elimination of the autoantibodies. When the concentration of IgG in
      the plasma reaches 200% of the normal value, for example, the fractional
      catabolic rate increases up to 180% of its normal value. In other words, the half
      life of IgG is decreased from 21 days to 12 days.

PMID- 8155251
TI  - Relationship between collagen-induced and adjuvant arthritis in the Lewis rat.
AB  - Adjuvant arthritis (AA) and type II collagen (CII)-induced arthritis (CIA) in the
      rat serve as models of chronic human arthritis. Adoptive transfer of AA was
      observed in 21 of 25 Lewis rats given concanavalin A (Con A)-treated spleen cells
      prepared from animals immunized with Mycobacterium butyricum in mineral oil
      (complete Freund's adjuvant, CFA). No arthritic changes were noted in rats given
      spleen cells obtained from donors that had received incomplete Freund's adjuvant
      (IFA, 0/22), type I collagen in IFA (CI-IFA, 0/6) or CII-IFA (0/28).
      Administration of spleen cells from IFA, CI-IFA or CII-IFA-injected animals did
      not modify the development of CIA when these rats were subsequently challenged
      with CII-IFA. However, partial protection against induction of AA was provided by
      the transfer of spleen cells prepared from rats immunized with CII-IFA (6/11) but
      not by those obtained from rats injected with IFA (1/15) or CI-IFA (0/3). Rats
      that did not develop clinically evident arthritis following the administration of
      spleen cells prepared from CFA-injected rats were also resistant to AA induction
      by CFA. Pre-treatment of rats with a synthetic peptide, corresponding to amino
      acids 180-188 of the Mycobacterium 65 kD heat shock protein (65 kD HSP),
      significantly delayed the onset of AA, but not that of CIA. Disease-specific
      resistance to AA, provided by spleen cells prepared from rats injected with CII
      IFA and by pre-treatment with the 65 kD HSP 180-188 peptide, may result from the
      induction of protective tolerance to arthritogenic epitopes present in the
      Mycobacterium and CII preparations.

PMID- 8155252
TI  - Induction of skin fibrosis and autoantibodies by infusion of immunocompetent
      cells from tight skin mice into C57BL/6 Pa/Pa mice.
AB  - Tight skin (TSK/+) mice develop a cutaneous hyperplasia associated with the
      occurrence of autoantibodies characteristic for scleroderma. In order to study
      the role of autoimmunity in the production of skin fibrosis, we conducted
      adoptive transfer experiments in which bone marrow cells of TSK/pa mice were
      infused into pa/pa mice littermates. (C57BL/6 pa/pa mice are used to produce
      heterozygous TSK/pa mice). Our results showed that after a prodromal period of
      several months, the transfer of bone marrow cells led to skin fibrosis, the
      presence of autoantibodies, and increased transcription of (alpha 1) collagen I
      and TGF beta genes. Infusion of enriched B or T cells alone did not cause skin
      fibrosis but of B cells alone increased autoantibody production. By contrast,
      transfer of T and B lymphocytes led to earlier mild fibrosis, cellular
      infiltration and autoantibody production as well as increased transcription of
      the (alpha 1) collagen gene. Our results strongly demonstrate, for the first
      time, that immunocompetent cells can play a role in the activation of collagen
      synthesis leading to skin fibrosis.

PMID- 8155253
TI  - Effects of cytokine application on glucocorticoid secretion in an animal model
      for systemic scleroderma.
AB  - We previously reported on an altered immune-endocrine feedback loop via the
      hypothalamo-pituitary-adrenal (HPA) axis in Obese strain (OS) chickens afflicted
      with spontaneous autoimmune thyroiditis. These animals are deficient in plasma
      corticosterone increase after antigenic challenge or application of cytokine
      containing conditioned medium of mitogen-stimulated spleen cells (CM). To
      investigate whether the impaired ability to respond to cytokines with
      glucocorticoid-increasing factor (GIF) activity, e.g. interleukin 1 (IL 1), is
      restricted to OS chickens as a model for an organ-specific autoimmune disease, we
      extended our experiments to another autoimmune-prone animal strain, the chickens
      of the University of California at Davis line 200 (UCD-200). These animals
      develop an inherited inflammatory fibrotic disease that closely resembles human
      progressive systemic sclerosis (scleroderma). Application of GIF-containing CM to
      UCD-200 chickens leads to a transient increase in glucocorticoid serum levels
      within 1-2 hours comparable to that of controls. But, while corticosterone levels
      in the latter returned to normal baseline levels after 4 hours, they were still
      elevated in autoimmune chickens. Although the peak of the glucocorticoid hormone
      serum concentrations was equal to that of controls, UCD-200 had to secrete twice
      as much adrenocorticotropic hormone to achieve this corticosterone serum level
      due to an apparent hyporesponsiveness of the adrenal gland to this secretagogue.
      The altered cytokine-induced glucocorticoid secretion is found in early as well
      as in chronic, sclerotic stages of the disease. Cellular alterations in the
      peripheral blood of UCD-200 chickens during the prolonged elevated corticosterone
      section, i.e. between 2-4 hours after CM application, are characterized by a
      significant decrease in the percentage of CD4+ and CD8+ cells. Furthermore, a
      significant increase in B cells up to 24 hours with a maximum after 1 hour was
      found. The proliferative response to the mitogen concanavalin A of peripheral
      mononuclear cells was inversely correlated to the serum corticosterone level,
      showing a permanent decrease of 80-90% after 1-4 hours in autoimmune animals.
      This functional alteration in UCD-200 was accompanied by an 80% decrease in serum
      interleukin 2 (sIL 2) activity 4 hours after CM application. Twenty-four hours
      later an eight-fold increase in sIL 2 rebound activity was found, indicating that
      the inhibitory effect of corticosterone in UCD-200 chickens is not long-lasting.

PMID- 8155254
TI  - Effects of various environmental stress paradigms and adrenalectomy on the
      expression of autoimmune type 1 diabetes in the non-obese diabetic (NOD) mouse.
AB  - The effects of long-term chronic stress (induced by repeated restraint,
      overcrowding or both), short-term chronic stress (induced by a triad of stressors
      over a short period of time early in life) and adrenalectomy were investigated on
      the prevalence, on the degree of insulitis and various physiological and
      immunological parameters in the NOD mouse, a spontaneous model of type I-insulin
      dependent diabetes mellitus (IDDM). Long-term chronic stress, obtained by
      restraint once a week or overcrowding, significantly protected NOD females, while
      both applied concomitantly had only a tendency to protect against diabetes. In
      contrast, short-term chronic stress had no significant effect on diabetes
      expression, whereas adrenalectomy resulted in a trend toward accelerated diabetes
      onset. The various long-term chronic stress paradigms exerted different effects
      on the progression of insulitis: repeated restraint tended to protect against
      insulitis, overcrowding had no effect but, when associated with restraint,
      significantly counteracted the beneficial effect of restraint alone.
      Adrenalectomy and short-term chronic stress had no significant effect on the
      development of insulitis. Various parameters, such as body, thymus and spleen
      weights, thymus and spleen cellularities, mitogen-induced spleen cell
      proliferation and serum corticosterone levels were also studied under the various
      experimental conditions. Taken together, the observations suggest that stressors
      modulate the expression of spontaneous autoimmune diabetes by exerting
      pleiotropic effects on immune and/or inflammatory components at the pancreas
      level and on peripheral glucose metabolism.

PMID- 8155255
TI  - T-splenocytes from non-obese diabetic mice binding to xenogeneic pancreatic beta
      cells in vitro. Implication of the alpha/beta T-cell receptor and of major
      histocompatibility complex class II molecules from target cells.
AB  - As compared to several strains of control mice, NOD mice displayed an increased
      number (P < 10(-4)) of splenocytes binding in vitro to xenogeneic rat RIN cells
      or hamster HIT cells, but not to nine non-beta cell lines. The increased binding
      to RIN cells was abolished by competition with RIN membrane extracts. It was
      prevented by depletion of Thy 1-2+ splenocytes, and by blocking the T-cell
      receptor (TCR) complex with anti-CD3 MoAbs, anti-alpha/beta TCR MoAbs, or their
      F(ab)'2 fragments (P < 10(-3)), but not with anti-gamma/delta TCR MoAbs. Neither
      anti-V beta 8 nor anti-V beta 6 MoAbs modified the signal. MoAbs against rat MHC
      class II molecules, but not MoAbs against rat class I molecules, inhibited the
      increased RIN-adhesion of NOD splenocytes (P < 10(-3)). After 3 h or 8 h of co
      incubation, the number of RIN-binding splenocytes was not different between NOD
      and control mice, and class II molecules were undetectable on RIN cells. Class
      II+ RIN cells appeared after 20 h of coculture when the increased binding was
      also observed. When 10,000 rad-irradiated RIN cells were used for the co
      incubations, neither class II+ RIN cells nor the increased binding of NOD
      splenocytes were found. As revealed by immunofluorescence, MoAbs against rat
      class II molecules cross-reacted with 30% of NOD (but not of control)
      splenocytes. Conversely, anti-NOD class II MoAbs (but not MoAbs against non-NOD
      class II molecules) cross-reacted with 20% of RIN cells coincubated with
      splenocytes. Thus, despite the species barrier, T-splenocytes from NOD mice
      display an increased adhesion to xenogeneic beta-cells. This binding involves T
      splenocytes bearing alpha/beta TCRs and RIN cells induced to express MHC class II
      molecules. MHC restriction may be completely absent in this phenomenon.
      Alternatively, the rat class II products may be directly recognized by NOD T
      cells in a xenograft context, and this model may therefore be useful toward the
      comprehension of some mechanisms leading to the rejection of islet
      xenotransplants. Finally, because of a cross-reaction with I-Anod, these rat
      Class II molecules may also either be directly recognized by I-A autoreactive NOD
      T cells or present RIN peptides to NOD alpha/beta TCRs, and thus would be
      relevant to the debated ability of beta cells to function as antigen-presenting
      cells.

PMID- 8155256
TI  - Treatment of multiple sclerosis with anti-CD4 monoclonal antibody. A preliminary
      report on B-F5 in 21 patients.
AB  - Twenty-one patients with definite active multiple sclerosis (MS) were treated
      with a monoclonal anti-T CD4/B-F5 (murine IgG1) antibody for 10 days. Side
      effects were observed in 11 patients during the first infusion. These side
      effects were accompanied by and probably related to a transient increase in IL6
      and TNF alpha serum levels. This problem led to treatment interruption in one
      patient. Neither clinical improvement nor deterioration was observed in the
      course of treatment. EDSS improvement (> 1 point) occurred in six patients one
      month post-treatment. One month after the end of treatment total lymphocytes and
      CD3+ and CD4+ cells were significantly decreased. Cytokine analysis performed in
      serum and in CSF before and after treatment showed no induced modifications. Ten
      patients developed xenogenic antibodies. It is of interest that the patients with
      relapsing-remitting forms were relapse-free at the 6th month post-therapy.

PMID- 8155257
TI  - Insulin (auto)antibodies from human IDDM cross-react with retroviral antigen p73.
AB  - In NOD mice, endogenous retroviruses including intracisternal type A particles
      (IAP) are expressed in the pancreatic beta cells. Furthermore, in these mice,
      insulin autoantibodies (IAA) cross-react with retroviral protein p73 (the IAP gag
      gene product), suggesting molecular mimicry between insulin and p73. We therefore
      investigated whether IAA and insulin antibodies (IA) associated with human IDDM
      cross-reacted with p73. Fifty IAA positive sera from 30 newly diagnosed IDDM
      before insulin therapy and 20 non-diabetic first degree relatives of IDDM and 27
      IA positive sera from insulin treated IDDM, initially defined as IAA or IA
      positive by radioimmunoassay, were evaluated. Binding to insulin and to p73 of
      these sera were analysed by ELISA. Approximately 65% of sera which bound insulin
      by ELISA also bound p73. Only one sample negative for insulin binding was
      positive for p73 binding. Preabsorption with either insulin or p73 inhibited
      binding to both insulin and p73. However, preabsorption with mouse hemoglobin had
      no effect on their binding. Repeat measurement of binding to insulin and p73 in
      10 non-diabetic first degree relatives of IDDM over an average of 16.6 months
      showed that each individual's reactivity to insulin and to p73 was relatively
      stable over time. Furthermore, in different individuals, binding to p73 and to
      insulin was closely correlated over time. In addition, 75 healthy teenagers (IAA
      negative by RIA) were used as normal controls in this study. p73 binding was
      found in only two (2.7%) of the 75 subjects. These results indicate that
      approximately 65% of ELISA (+) IAA and IA subjects have antibodies which
      recognize both insulin and p73, suggesting that IAA and IA from some subjects
      recognize an epitope shared between human insulin and the murine gag gene
      product. This raises the possibility that for some subjects who are IAA positive,
      the immunizing antigen may be antigenically similar to p73, rather than insulin,
      and that endogenous retroviruses may be involved in human IDDM.

PMID- 8155259
TI  - In-situ preferential usage of V alpha 8 T-cell receptor gene segments in a
      patient with bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with
      the occurrence of autoantibodies directed to a limited series of antigens located
      at the basement membrane zone of the dermo-epidermal junction. Previous studies
      have demonstrated the presence of activated T cells in BP lesions although their
      actual contribution to the pathogenesis of the disease has remained unclear. One
      approach to better understanding the significance of these T-cell infiltrates is
      to study the diversity of the recognition receptors (TCRs) expressed at the
      lesion sites. We report here an extensive analysis, performed in one patient with
      typical BP, where 187 TCR in frame transcripts from a lesional area, from
      clinically normal skin or from peripheral blood lymphocytes have been sequenced
      and compared. The data show preferential usage of the V alpha 8 subfamily gene
      segments in the lesion. It is therefore suggested that T-cell infiltration in BP
      may not simply reflect a non-specific inflammatory process but include antigen
      specific responses.

PMID- 8155258
TI  - Utilization of the VH4-21 gene segment by anti-DNA antibodies from patients with
      systemic lupus erythematosus.
AB  - A monoclonal antibody (9G4) which detects an idiotope (Id) rising from heavy
      chains encoded by the VH4-21 gene segment has been utilized to investigate the
      role of this gene in encoding anti-DNA antibodies in SLE. Two hybridomas
      secreting Id-positive anti-DNA antibodies were established from two patients with
      SLE, with one (RT-79) an IgM kappa and the other (D-5) IgG kappa. Nucleotide
      sequence analysis of the heavy chain variable regions revealed involvement of the
      VH4-21 gene; the IgM antibody used the gene in germ line configuration, whereas
      the IgG antibody had 18 nucleotide changes. The CDR3 sequences for both the
      antibodies had a predominance of basic amino acids, with RT-79 having five and D
      5 two arginine residues respectively. The VH4-21 gene segment, often in germ line
      configuration, is also used by IgM autoantibodies against red cell Ii antigens.
      However, IgM from a panel of six hybridomas secreting antibodies of Ii
      specificity, had no detectable activity against DNA. Conversely, RT-79 had only a
      weak ability to agglutinate red cells. Comparisons of Ig variable regions
      indicate that the amino acids in the CDR3 region of the mu chain influence the
      ability of IgM encoded by the VH4-21 gene segment to discriminate between a
      carbohydrate Ii antigen and DNA, and strongly support the suggested role of
      arginine in interaction with DNA. Sera from patients with SLE were found to have
      significantly raised levels of Id which was expressed by anti-DNA antibodies
      against both ss and dsDNA.

PMID- 8155260
TI  - Are we closer to selective immunotherapy for autoimmune diseases?
AB  - The discipline of immunotherapy has promised much in the restricted confines of
      the laboratory but, so far, has delivered little in the harsh reality of the
      clinic. At a recent conference to celebrate the opening of Roche Milano
      Ricerche*, the hopes, successes and failures in this complex field were presented
      for examination.

PMID- 8155261
TI  - Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now?
AB  - Vaccination with tumor cells that have been engineered to express cytokine genes
      has been developed in animal models as a novel form of tumor therapy. Mario
      Colombo and Guido Forni assess the current situation and suggest a way forward.

PMID- 8155262
TI  - Fc epsilon RI on human Langerhans cells: a receptor in search of new functions.
AB  - The recent demonstration that the high-affinity receptor for IgE, Fc epsilon RI,
      is expressed on human Langerhans cells casts a new perspective on the function of
      this receptor. This observation also provides a new direction for further
      investigation into the pathophysiological relevance of Langerhans cells and other
      antigen-presenting cells in the development of atopic diseases.

PMID- 8155263
TI  - Simplifying genetic locus assignment of HLA-DRB genes.
AB  - The DR haplotypes of the human major histocompatibility complex have been
      arranged in five haplotypic groups based on genomic cloning and sequence
      analyses. To date, the expressed DRB sequences have been assigned to four
      different loci: DRB1, 3, 4 and 5. DRB1 alleles are present in all haplotypes,
      whereas DRB3, 4 and 5 are present only in some haplotypes. Here, Goran Andersson
      and colleagues suggest that DRB3, 4 and 5 sequences may be treated as a single
      allelic series. They argue that such a model is appropriate, since DRB3, 4 and 5
      sequences are inherited in an allelic fashion, have similar genomic localization,
      exhibit similar levels of gene expression and are, with a few rare exceptions,
      not present in the same haplotype.

PMID- 8155264
TI  - Adhesion molecules as regulators of mast-cell and basophil function.
AB  - Basophils and mast cells play a role both in immediate allergic reactions and in
      inflammation. Both types of cells have surface adhesion receptors that can
      mediate binding to other cells and to extracellular matrix glycoproteins. Here
      Majed Hamawy and colleagues discuss the importance of these adhesion molecules in
      regulating basophil and mast-cell functions.

PMID- 8155265
TI  - Collectins: collagenous C-type lectins of the innate immune defense system.
AB  - Collectins are humoral lectins found in mammals and birds. They are oligomers
      whose subunits comprise three polypeptide chains each containing a collagenous
      section and a C-terminal lectin domain. They are related structurally and
      functionally to the first component of the classical complement pathway, C1q, and
      seem to serve important roles in innate immunity through opsonization and
      complement activation. The lectin domains bind carbohydrates on microorganisms,
      while the collagenous regions are ligands for the collectin receptor on
      phagocytes and also mediate C1q-independent activation of the classical
      complement pathway.

PMID- 8155266
TI  - The major acute phase reactants: C-reactive protein, serum amyloid P component
      and serum amyloid A protein.
AB  - Following an acute phase stimulus, such as infection or physical injury, many
      liver-derived plasma proteins are increased in concentration. These provide
      enhanced protection against invading micro-organisms, limit tissue damage and
      promote a rapid return to homeostasis. Diana Steel and Alexander Whitehead
      discuss the gene structure, regulation and possible clinical significance of the
      most dramatically induced acute phase reactants.

PMID- 8155267
TI  - Surface-bound cytokines--a possible effector-mechanism in bacterial immunity.

PMID- 8155268
TI  - Dynamics of the autoimmune T-cell repertoire in experimental allergic
      encephalomyelitis and in multiple sclerosis.

PMID- 8155269
TI  - Immunization of macaque monkeys with low- and high-dose regimens of SIVmac
      results in different immune responses.

PMID- 8155270
TI  - [Free radicals].
AB  - Free radicals are continuously threatening living organs. Firstly generated by
      endogenic pathway during normal and vital metabolic reactions, they can be also
      produced by environmental factors: atmospheric pollution, radiations... An
      energetic source ensures the initiation of free radicals reaction. Its expanding
      is strengthened by oxygen (bi-radical form) and transition metals (chiefly iron).
      Eyes are very sensitive organs to the deleterious action from the oxygen active
      species. Protection systems against free radicals action are necessary in living
      cells. A part the pathologic or ageing conditions, oxygen toxicity doesn't; in
      fact, neutralised by protection systems coming from enzymes (endogenic way) and
      food contribution: vitamins, carotenoids, flavonoids... (exogenic way).

PMID- 8155271
TI  - [Measurement of interferon gamma (gamma IFN) and interleukin 4 (IL4) in asthma
      and atopic dermatitis].
AB  - The recent contributions to the mechanisms of regulation of IgE by cytokines has
      produced development of kits that are usable in IFN gamma in atopic dermatitis
      where we have fixed a significant basal level in contrast to a reference group,
      though there is no possibility of making a modification in asthma. However, this
      seems to us to be logical since this change of IFN gamma was studied in
      peripheral blood when the study should be made of broncho-alveolar lavage in
      asthma. The assay kits for IL4 lack performance and "realism" in their threshold
      level of detection. This study has also given comparison of the variation of the
      two cytokines in comparison with total and specific IgE.

PMID- 8155272
TI  - Case report: recurrent anaphylactic shock to radiographic contrast media.
      Evidence supporting an exceptional IgE-mediated reaction.
AB  - A rare case of anaphylaxis to iodinated contrast media is reported. The patient
      underwent two anaphylactic shocks to intravenous administration of radiocontrast
      agents. Specific IgE were suspected on the basis of positivity of intradermal
      tests and human basophil degranulation tests. The passive sensitization of
      basophils from donors was performed, comparing native and heated serum. Results
      agreed with the hypothesis of IgE antibodies, since heating 56 degrees C during
      two hours prevented the degranulation. Considering the chemical structure,
      iopamidol was thought to be innocuous. Two opacification procedures were further
      performed with iopamidol without any incident.

PMID- 8155273
TI  - Immunotherapy for respiratory allergic diseases: indications, efficacy and
      monitoring.
AB  - The author reports a detailed analysis of the indications for Specific Immuno
      Therapy (SIT) in allergic rhinitis and asthma. After pointing out the
      requirements for a correct clinical trial, the efficacy of SIT towards various
      allergenic agents is examined (pollen, mites, cat and dog danders, moulds).
      Clinical monitoring--by means of clinical diaries, symptom score, drug
      consumption, skin tests, challenge tests--and immunological monitoring--by means
      of measuring of IgE and IgG serum antibodies, mediator and cytokine release,
      lymphocyte study, etc.--are then discussed. Immunological and clinical parameters
      to evaluate the efficacy of SIT are compared: clinical parameters being the most
      effective means of evaluation of clinical improvement.

PMID- 8155274
TI  - Toxicologic testing of inhaled pharmaceutical aerosols.
AB  - This paper reviews technical issues related to the toxicologic testing of inhaled
      pharmaceuticals. Although there are commonalities between approaches to general
      and inhalation toxicity testing, there also are specific challenges in the
      toxicity testing of inhaled pharmaceuticals. A major issue is that of dose;
      inhaled dose is more difficult to determine than intravenous or oral doses. Also,
      it is harder to relate dose in laboratory animals to that in man for inhalation
      exposure than for other routes of administration. Additionally, in the case of
      inhaled pharmaceuticals, people generally inhale through the mouth, whereas most
      laboratory animals inhale primarily through the nose. This presents significant
      challenges in exposure methodology and technology that often need innovative
      approaches involving alteration to particle size of the agent or dosing
      procedure. Because the respiratory tract is the site of deposition, local
      respiratory toxicity and possible damage to lung cells need to be assessed.
      Systemic toxicity also needs to be evaluated and may be an issue in some cases.
      Special studies on pulmonary function, mucociliary clearance, or immune response
      may be needed, depending on the nature of the inhaled pharmaceutical. This review
      explores the main issues involved in toxicity testing of inhaled pharmaceuticals,
      the approaches that have been used, and the current and future challenges.

PMID- 8155275
TI  - The pharmacology of the nootropics; new insights and new questions.
AB  - Up to now, the memory-enhancing effect of the nootropics has chiefly been
      investigated in the context of effects on energy metabolism and on cholinergic
      and glutamatergic neurotransmission. Recent studies have also shown that the
      effect on memory is steroid-sensitive. The present review article summarizes the
      available results and discusses them in the context of a new hypothesis on the
      mechanism of action and with respect to clinical implications.

PMID- 8155276
TI  - Stimulus configuration, spatial learning, and hippocampal function.
AB  - Schmajuk and DiCarlo (Psychol. Rev., 99 (1992) 268-305) introduced a neural
      network, which utilizes a biologically plausible backpropagation procedure, to
      describe configural paradigms in classical conditioning. The model correctly
      describes many experimental results under the assumption that aspiration lesions
      of the hippocampus eliminate (a) the competition between simple and configural
      stimuli to gain association with the unconditioned stimulus and (b) the
      adjustment of initially random configural stimuli. The present study extends the
      network to describe place learning. Under the assumption that ibotenic acid
      lesions of the hippocampus only impair the adjustment of initially random
      configural stimuli, the model correctly shows that ibotenic acid lesions might
      spare a configural discrimination but impair place learning. In general, the
      results are taken to support a hippocampal role in the modulation of stimulus
      configuration.

PMID- 8155277
TI  - Lesions of the central nucleus of the amygdala. I: Effects on taste reactivity,
      taste aversion learning and sodium appetite.
AB  - Bilateral damage to the central nucleus of the amygdala (CeAX) in the rat blunts
      need-induced NaCl intake and abolishes daily need-free NaCl intake when measured
      with a two-bottle test. Such a deficit could be the result of impaired taste
      function. To assess the taste function of the CeAX rat various taste stimuli were
      introduced directly into the oral cavity and taste-elicited oral motor responses
      were measured. Oral motor responses elicited by 0.62 M and 0.13 M sodium
      chloride, 0.3 M sucrose and 0.01 M citric acid, were similar in control and CeAX
      rats. Additionally CeAX and control rats acquired a taste aversion for fructose
      or maltose when either was paired with LiCl. Finally, in CeAX rats, like in
      control rats, the pattern of oral motor responses to 0.5 M NaCl was dependent on
      internal state; sodium depletion dramatically altered taste-elicited oral motor
      behavior. These results suggest that, in the rat, the deficits in NaCl intake
      behavior that follow CeAX do not appear to be a result of dramatic changes in
      gustatory function.

PMID- 8155278
TI  - Female specific hyperactivity in S100 beta transgenic mice does not habituate in
      open-field.
AB  - S100 beta, a calcium-binding brain specific protein, may affect brain development
      and long-term potentiation. Its gene maps to a region of chromosome 21 duplicated
      in Down's Syndrome (DS), and its levels are elevated in DS. To test the
      hypothesis that elevated S100 beta levels cause brain dysfunction in a mammalian
      system, transgenic mice carrying multiple copies of the human S100 beta gene have
      been generated and their locomotory patterns are analyzed in open field
      situations. Female-specific hyperactivity was observed in 2-month-old and in 12
      month-old transgenic mice, which rules out the previous speculation that
      postmenopausal hormonal changes constitute a necessary factor in this behavioral
      abnormality. Analysis of temporal patterns of activity showed a profound
      abnormality in transgenic females: the initially elevated activity quickly
      habituated in males and in normal females, however, its level remained high in
      the transgenic females throughout the 9-min recording session. These observations
      are compatible with the suggestion that hippocampal function is abnormal in the
      females of S100 beta transgenic mice.

PMID- 8155279
TI  - Post-reactivation cocaine administration facilitates later acquisition of an
      avoidance response in rats.
AB  - We previously demonstrated that cocaine administered immediately prior to a
      reactivation episode comprised of re-exposure to selected features of the
      original fear-conditioning session alters subsequent memory retrieval or
      reconsolidation. In the present study we determined that, similar to pre
      reactivation administration, post-reactivation administration of cocaine also
      alters memory retrieval or reorganization, as measured by subsequent conditioned
      performance. The dose-response function for this effect of cocaine was U-shaped;
      maximal enhancement of subsequent avoidance performance was produced by a 7.5
      mg/kg i.p. dose of cocaine. Because a dose of lidocaine equimolar to the
      effective cocaine dose was found not to alter subsequent conditioned performance,
      the effect of cocaine on memory processing most likely is not attributable to its
      local anesthetic properties.

PMID- 8155280
TI  - GABAergic nigro-collicular pathways modulate the defensive behaviour elicited by
      midbrain tectum stimulation.
AB  - Midbrain tectum (MT) structures such as the dorsal periaqueductal gray matter and
      deep layers of superior colliculus are well-known for the organization and
      generation of defensive behaviour. Electrical stimulation or microinjection of
      GABA antagonists into these structures produce aversive behaviour. In order to
      determine whether the nigrocollicular GABAergic fibers exert some control over
      this behaviour, rats bearing neurochemical lesions with kainic acid in the
      substantia nigra, pars reticulata (SNpr) and compacta (SNpc), were submitted to
      MT microinjections of bicuculline or electrical stimulation at aversive
      thresholds. The same procedure was carried out after enhancement or inhibition of
      GABAergic transmission in SNpr through microinjections of muscimol or
      bicuculline, respectively. Animals with SNpr neurochemical lesion exhibited a
      significant decrease in the aversive thresholds and an increase in the
      responsiveness to bicuculline microinjections. An opposite effect was observed
      following microinjections of bicuculline into the SNpr. The enhancement of the
      GABAergic transmission into the SNpr following microinjection of muscimol
      mimicked the effects produced by the lesion with kainic acid. These results
      suggest an inhibitory control of GABAergic fibers from the substantia nigra, pars
      reticulata, on aversive behaviour induced by midbrain stimulation.

PMID- 8155282
TI  - Wistar-Kyoto rats in the Morris water maze: impaired working memory and hyper
      reactivity to stress.
AB  - Wistar-Kyoto (WKY) rats were tested as a potential animal model for memory
      dysfunction. These animals were reported to be highly reactive to stress and this
      was associated with findings of alterations in their hippocampal cholinergic
      activity. Since hippocampal cholinergic hypofunction is often associated with
      deficits in memory processes, untreated WKY rats were tested here in a working
      memory task in the Morris water maze. Animals were tested for five daily
      sessions, with two identical trials per day, and their performance was compared
      to that of Sprague-Dawley (SD) rats. Results show that WKY rats failed to improve
      their performance both from day to day and within the two trials each day. This
      suggests impaired memory capabilities of WKY rats and may support their use as an
      animal model of memory dysfunction. However, because of their increased tendency
      to float, speed of performance was also reduced in WKY compared to SD rats. This
      difference may be associated with their increased reactivity to stress. The
      combination of memory dysfunction and stress hyper-reactivity seen in WKY rats
      may be used to study the association between these two functions, particularly
      the possible interaction between memory and depression.

PMID- 8155281
TI  - Absence of amnestic effect of an anxiolytic 5-HT3 antagonist (BRL 46470A)
      injected into basolateral amygdala, as opposed to diazepam.
AB  - This experiment compares the effects of microinjections into the basolateral
      amygdala nucleus of diazepam (DZP) and a new 5-HT3 receptor antagonist, BRL
      46470A, on acquisition and retention of an inhibitory avoidance tasks by rats.
      The animals were microinjected with DZP or BRL 46470A between 10 and 15 min
      before the learning trial. Retention testing 48 h later showed impaired retention
      in animals injected with DZP but not with BRL 46470A. These results show that BRL
      46470A, a compound suggested to have anxiolytic effects does not induce amnesia.
      This evidence for a possible dissociation between anxiety-reducing and memory
      disrupting effects of a drug has implications, for one, for the understanding of
      the neuronal substrates mediating these effects, and secondly, for the search for
      anxiolytic agents devoid of undesirable side effects on memory processes.

PMID- 8155283
TI  - Amygdala modulates memory for changes in reward magnitude: reversible post
      training inactivation with lidocaine attenuates the response to a reduction in
      reward.
AB  - The present study used a reward reduction paradigm to examine the role of the
      amygdala in memory for reduction in reward magnitude. Male Sprague-Dawley rats
      were implanted with bilateral amygdala cannulae and trained to run a straight
      alley (6 trials/day) for either ten or one 45-mg food pellets. On Day 10 of
      training, half the animals in the 10 pellet reward group were shifted to a one
      pellet reward. Immediately following shifted trials, the animals received an
      intra-amygdala injection of either a 2% lidocaine solution or phosphate buffer
      (0.5 microliter/side). Shifted training continued for 2 more days and no further
      injections were given. Shifted animals that received a buffer injection displayed
      a sharp increase in response latencies compared to unshifted controls on the
      second day of shifted training. In contrast, shifted animals that received intra
      amygdala injections of lidocaine exhibited significantly lower latencies compared
      to the shifted vehicle group on the second day of shifted training. The findings
      indicate that post-training inactivation of the amygdala attenuates the response
      to reward reduction, suggesting that the amygdala modulates the storage for a
      reduction in reward magnitude.

PMID- 8155284
TI  - The effects of number of stimuli and prior exposure on performance of concurrent
      visual discriminations during suppression of inferotemporal cortex with cold.
AB  - The visual part of the temporal cortex, cytoarchitectural area TE has been split
      into dorsal (TEd) and ventral (TEv) subdivisions. TE has long been associated
      with the identification of objects. However, in order to explain retrieval
      deficits with suppression of prestriate cortex, but not with suppression of TE,
      we hypothesized that object identification might take place in a working memory
      in the prestriate cortex upstream from TE. Exposure to the stimuli before
      suppressing TEd was hypothesized to cause its contribution to be relayed to
      prestriate cortex in anticipation of further work with them. This predicts that
      during TEd suppression there is a loss of access to some long-term visual memory,
      and without that access, large numbers of stimuli should overwhelm the limited
      capacity working memory. It also predicts that prior exposure to stimuli should
      protect them from loss during TEd suppression. We challenged these predictions in
      two experiments. In the first, we tested the animals on three concurrent
      discriminations requiring them to retrieve 8 pairs of stimuli for each one. The
      animals performed well on some of the discriminations during TEd suppression, but
      failed on others, which is consistent with the prediction. Also, different
      animals failed with different stimuli. However, when we tested with only the
      failed discriminations, they still did badly with one or two pairs, which is not
      consistent with the prediction. In the second experiment, we tested them with 1,
      4, 7 or 10 pairs of visual discriminations drawn from a set of 23 the animals had
      learned. Half of the discriminations were presented immediately before
      suppression and half were not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155285
TI  - Selective cognitive impairment following traumatic brain injury in rats.
AB  - Impairment of cognitive abilities is a frequent and significant sequelae of
      traumatic brain injury (TBI). The purpose of this experiment was to examine the
      generality of the cognitive deficits observed after TBI. The performance of three
      tasks was evaluated. Two of the tasks (passive avoidance and a constant-start
      version of the Morris water maze) were chosen because they do not depend on
      hippocampal processing. The third task examined was the standard version of the
      Morris water maze which is known to rely on hippocampal processing. Rats were
      either injured at a moderate level (2.1 atm) of fluid percussion brain injury or
      surgically prepared but not injured (sham-injured control group). Nine days after
      fluid percussion injury, injured (n = 9) and sham-injured rats (n = 8) were
      trained on the one-trial passive avoidance task with retention assessed 24 h
      later. On days 11-15 following injury, injured (n = 9) and sham-injured (n = 8)
      rats were trained on a constant-start version of the Morris water maze that has
      the animals begin the maze from a fixed start position on each trial. Additional
      injured (n = 8) and sham-injured (n = 8) animals were trained on days 11-15 after
      injury on the standard (i.e. using variable start positions) version of the
      Morris water maze. The results of this experiment revealed that performance of
      the passive avoidance and the constant-start version of the Morris water maze
      were not impaired by fluid percussion TBI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155286
TI  - Lesions of the central nucleus of the amygdala. II: Effects on intraoral NaCl
      intake.
AB  - Bilateral lesions of the central nucleus of the amygdala (CeAX) disrupt both need
      free and need-induced NaCl intake. Quite surprisingly, in response to sodium
      depletion, the same rats who fail to augment their NaCl consumption dramatically
      increase the numbers of oral motor behaviors associated with ingestion that they
      display when NaCl is presented intraorally. The present study attempts to resolve
      these apparently contradictory results by measuring the intake of a NaCl solution
      delivered directly into the mouth. Controls enhanced their intraoral intake of
      0.5 M NaCl in response to sodium depletion while CeAX rats did not. CeAX rats,
      however, showed discriminative intake responses to tastes. Like controls, CeAX
      rats promptly rejected 0.3 mM quinine infusions and ingested 1.0 M sucrose for
      prolonged periods. In addition, food deprivation enhanced the intraoral intake of
      a dilute sucrose solution in both CeAX and control rats. Thus, in the CeAX rat
      some tastes and some internal states modulate intake as they do in intact rats.
      These results are consistent with the hypothesis that central nucleus of the
      amygdala damage interferes with the consummatory phase of NaCl intake behaviors.

PMID- 8155287
TI  - Effects of intracranial infusions of chlordiazepoxide on spatial learning in the
      Morris water maze. II. Neuropharmacological specificity.
AB  - In the preceding paper it was found that infusions of chlordiazepoxide (CDP) into
      the medial septal region, but not several other regions possessing a high density
      of benzodiazepine receptors, impaired spatial learning, but not cue learning or
      swim speed, in the Morris water maze. The present investigation sought to further
      characterize the neuropharmacological profile of this effect. Initially, it was
      reconfirmed that systemically administered CDP impaired spatial learning, but not
      cue learning or swim speed, in the water maze. Additionally, it was found that
      systemically administered scopolamine, a muscarinic antagonist, impaired both
      spatial and cue learning, but not swim speed, confirming the detrimental effects
      of cholinergic hypofunction on maze learning. In new rats, a dose-response
      assessment revealed that 60 and 30 nmol, but not 10 nmol, CDP infused into the
      medial septum impaired spatial learning, but not cue learning or swim speed. On
      the following day, rats from each dose group, now undrugged, acquired a reversed
      platform location at control levels, suggesting that the previously observed
      impairment was not due to a neurotoxic effect. Additionally, it was found that
      systemically administered flumazenil (10 mg/kg) blocked the spatial learning
      deficit produced by the 60 nmol dose of CDP infused into the medial septum.
      However, intraseptal infusions of flumazenil (10, 20, or 30 nmol) failed to
      attenuate the spatial learning deficit produced by systemically administered CDP.
      Finally, systemically administered tetrahydroaminoacridine (1 or 3 mg/kg), an
      acetylcholinesterase inhibitor, failed to attenuate the spatial learning deficit
      produced by intraseptal CDP (60 nmol). Together these results implicate
      benzodiazepine receptors in the medial septum in the amnesic actions of CDP but
      suggest that additional sites also mediate this action. The present results fail
      to support the idea that the spatial learning deficit produced by intraseptal
      infusions of CDP is due to a suppression of septo-hippocampal cholinergic
      activity and it is proposed that CDP impairs spatial learning by exacerbating
      hippocampal inhibition by inhibiting septo-hippocampal GABAergic projection
      neurons.

PMID- 8155288
TI  - The effect of early movement restriction: an EMG study in the rat.
AB  - The effect of early immobilization upon the adult locomotor pattern was studied.
      One hindlimb of neonatal rats was immobilized during 20 days and the EMG pattern
      was studied 3-8 weeks after termination of movement restriction. All rats showed
      a fluent locomotion pattern at these ages, but the EMG pattern revealed
      differences in the timing of flexor and extensor activity between the previously
      immobilized and the contralateral side. We suggest that interference with
      movement related afferent feedback at young ages has subtle but long-lasting
      effects upon the locomotion generating neural circuits.

PMID- 8155289
TI  - Correlative circadian rhythms of cholecystokinin and dopamine content in nucleus
      accumbens and striatum of rat brain.
AB  - Due to contrary results concerning the interaction of cholecystokinin and
      dopamine (CCK/DA) circadian variations in CCK/DA concentration were investigated
      in forebrain nuclei of rats (Nc. accumbens, striatum) in order to assess the
      influence of time of day on neurotransmission. CCK was determined by a
      radioimmunoassay, DA was measured by electrochemical detection after HPLC
      separation. A distinct circadian rhythm, superimposed by harmonics (12 h, 6 h)
      was found in the content of both DA and CCK. A trough was shown for CCK during
      the light phase and a crest during the late afternoon and the dark phase,
      respectively. For DA the opposite was found. Caused by a phase-shift of about 3-4
      h, the CCK/DA rhythms are negatively correlated. The differences are significant
      at 11.00 h, 13.00 h, 21.00 h, and 03.00 h. The results indicate that circadian
      processes are involved in neuronal transmission of CCK and DA.

PMID- 8155290
TI  - Effects of an early postnatal hypoxia on the development of spontaneous head
      movements in rabbits.
AB  - The early detection of minor brain dysfunctions resulting from perinatal hypoxia
      is very important since the prognosis of the affected children can be
      substantially improved by a prompt treatment. Therefore, this paper deals with
      the influence of an early postnatal hypoxia on the postnatal development of
      spontaneous head movements and the influence of the visual system on head
      movements in normal and hypoxic disturbed ontogenesis. Head movements were
      recorded in 12 unrestrained spontaneously behaving alert rabbits from 6 litters
      with the sensor coil technique. One rabbit of each litter was exposed to a single
      acute hypoxia (FiO2 = 0.05) for 3 h at the 1st day of life. The siblings were
      regarded as a control group. The most important characteristic of the postnatal
      development of the head movements is the forming of horizontal saccadic movements
      during the second postnatal week and their perfection by an increase in mean
      velocity up to the 20th postnatal day. The early postnatal hypoxia leads to a
      decrease of the mean velocity of saccadic head movements. But this is only true
      if the rabbits have open eyes. Blind-folding the rabbits of the control group
      during the recordings was followed by a decrease of the mean velocity (14th and
      20th postnatal day) and the amplitude (at the 20th postnatal day) of the saccadic
      head movements. In contrast to the non-hypoxic rabbits, blind-folding had no
      perceptible influence on head movements in hypoxic rabbits until the 3rd
      postnatal week. Our results suggest that early postnatal hypoxia causes a

PMID- 8155291
TI  - Localization of extratectally evoked visual response in the corpus and valvula
      cerebelli in carp, and cerebellar contribution to 'dorsal light reaction'
      behavior.
AB  - In carp with the optic tectum removed bilaterally, the optic nerve stimulation
      evoked a surface positive response on the cerebellum, which originated in the
      granular layer. In the corpus cerebelli, the response was composed of a single
      component, well localized at the rostromedial part, supporting previous
      electrophysiological and morphological findings. In the valvula cerebelli, on the
      other hand, the response consisted of two wave components of oligo-synaptic and
      poly-synaptic transmission. The former distributed diffusely and was comparable
      to the corporeal response, while the latter localized at the rostrolateral part
      of the ventral valvula. Dorsal light reaction (DLR), which remained after optic
      tectum ablation, was slightly impaired by a lesion of the visual projection area
      in the corpus cerebelli, but recovered within a few days. The impairment was
      marked due to a lesion of the valvula cerebelli and recovery was prolonged. When
      above lesions were combined, the impairment was not summative but recovered much
      earlier, suggesting a complex neural network for DLR regulation mechanism.

PMID- 8155292
TI  - D-amphetamine-like stimulus properties are produced by morphine injections into
      the ventral tegmental area but not into the nucleus accumbens.
AB  - We investigated whether injections of morphine into the ventral tegmental area
      (VTA) or the nucleus accumbens (NAS) could produce amphetamine-like stimulus
      properties and locomotor stimulant effects. Rats were trained to discriminate 1.0
      mg/kg D-amphetamine from saline using both VI-30 and FR-16 reinforcement
      schedules and they were then tested following bilateral injections of morphine
      sulfate (2.5, 5.0 and 10.0 micrograms/side) either into the VTA or the NAS. Intra
      VTA injections of morphine produced significant increases in amphetamine-lever
      responding that were comparable to increases observed following intra-NAS D
      amphetamine (2.5, 5.0 and 10.0 micrograms/side). Such increases were not
      observed, however, following intra-NAS injections of morphine. Tests for the
      effects of intracerebral morphine and D-amphetamine on locomotor activity
      produced a similar pattern of results. Locomotor activity was increased following
      intra-VTA morphine and intra-NAS D-amphetamine injections, but not after intra
      NAS morphine injections. Together, these findings indicate that activation of
      opioid receptors within the VTA, but not the NAS, can produce a behavioral state
      which mimics to some degree the state produced by systemic and intra-NAS
      injections of D-amphetamine.

PMID- 8155293
TI  - A quantitative estimate of the role of striatal D-2 receptor proliferation in
      dopaminergic behavioral supersensitivity: the contribution of mesolimbic dopamine
      to the magnitude of 6-OHDA lesion-induced agonist sensitivity in the rat.
AB  - Rats with unilateral depletions of neostriatal dopamine display increased
      sensitivity to dopamine agonists estimated to be 30 to 100 x in the 6
      hydroxydopamine (6-OHDA) rotational model. Given that mild striatal dopamine D-2
      receptor proliferation occurs (20-40%), it is difficult to explain the extent of
      behavioral supersensitivity by a simple increase in receptor density. This study
      was designed to investigate the quantitative aspects of the rotational behavior
      model utilizing constrained non-linear curve fitting routines. A dose-response
      curve for the rotational response arising from apomorphine stimulation of the
      normosensitive striatum was obtained in animals bearing unilateral lesions of
      striatal efferents (predominantly the striato-nigral pathway as previously
      described). After the control dose-response experiment, rats received a dopamine-
      (DA) depleting lesion in the contralateral hemisphere. In one group, 6-OHDA was
      infused into the medial forebrain bundle (MFB), a placement which is common in
      the literature and is known to deplete DA in both the striatum and nucleus
      accumbens. In a second group of rats, 6-OHDA was infused into the globus pallidus
      at a site which depletes caudate DA, but leaves n. accumbens DA relatively
      intact. The two experimental groups were tested in identical apomorphine-induced
      rotation dose-response experiments. The ED50's of the MFB- and caudate-lesioned
      rats were reduced by 36 and 5.8 fold, respectively, as compared to the control
      dose-response curve. The MFB and caudate lesions depleted striatal DA and
      produced a 30 and 36% increase in striatal D-2 binding sites, respectively.
      Modeling the behavioral and biochemical data with the null model for receptor
      occlusion indicated that increased striatal D-2 receptor density could account
      for the magnitude of behavioral supersensitivity in neither the MFB-lesioned
      group, nor even in the caudate-lesioned group. Thus simple up-regulation or D-2
      receptors is unlikely to account for supersensitization as measured in the
      rotational model. Further, we suggest that quantitative modeling of such
      hypotheses is a valuable experimental technique for assessing relationships
      between biochemical and behavioral variables.

PMID- 8155294
TI  - Spared short-term memory in monkeys following medial temporal lobe lesions is not
      yet established: a reply to Alvarez-Royo, Zola-Morgan and Squire.
AB  - It is important to know whether or not short-term memory (STM) is preserved in
      monkeys, as sometimes claimed, following lesions to medial temporal lobe that
      disrupt longer term memory. As examined herein, the magnitude of the longer term
      deficit in the delayed matching-to-sample task is well correlated with slower
      learning at short delays. This learning deficiency with short delays can be
      severe, e.g., failure to reach criterion despite ten times the number of trials
      required by control animals, yet the same animals can perform some visual
      discriminations normally. Such slow learning may thus be most parsimoniously
      attributed to a STM deficit. Studies are also reviewed which compare delayed
      (non)matching-to-sample performance in lesioned monkeys at short and long delays.
      For those groups that received equal training at all delays, the short-term
      deficit is as large as the longer term deficit. For those groups trained only at
      the short delay the short-term deficit is small. Caveats for future studies are
      discussed.

PMID- 8155295
TI  - Amelioration of sensory attention and sensorimotor deficits by chromaffin cell
      grafts to the cerebral cortex of nucleus basalis magnocellularis lesioned rats.
AB  - Rats that have received lesions to the nucleus basalis magnocellularis display
      with a variety of behavioral deficits; among these are decreases in performance
      of maze tests as well as deficiencies on measures of general health, sensory
      attention and sensorimotor abilities. We have previously shown that grafts of
      chromaffin cells placed in the cerebral cortex of nucleus basalis magnocellularis
      lesioned rats can ameliorate the lesion-induced deficits in performance of a task
      involving spatial memory. In the present study, we find that lesion-induced
      deficits in the sensory attention measure of exploration of the environment (head
      scanning) as well as the sensorimotor behavior involving a rat righting itself
      when placed nose down on an inclined grid are evident at 8 weeks post-lesion in
      lesioned-alone rats; these deficits are significantly ameliorated by chromaffin
      cell grafts in the cerebral cortex placed two weeks following the lesion
      procedure. These findings may have relevance to the use of chromaffin cells for
      grafting in neurodegenerative disorders in which sensorimotor or attention
      deficit components are involved.

PMID- 8155296
TI  - Studies on the behavioral activation produced by stimulation of GABAB receptors
      in the median raphe nucleus.
AB  - Injections of the GABAB agonist baclofen into the median raphe nucleus (MR)
      resulted in marked hyperactivity and in increases in food and water intake by non
      deprived animals. The locomotor effects of baclofen were stereospecific and could
      be antagonized by coinjection of the GABAB antagonist 2-hydroxysaclofen.
      Hyperactivity was produced by lower doses of baclofen, at shorter latencies, when
      the drug was injected into the MR than when it applied to the dorsal raphe
      nucleus (DR) or the ventral tegmental area (VTA). The locomotor response to intra
      MR baclofen was unaltered in animals pretreated with the serotonin synthesis
      inhibitor p-chlorophenylalanine. Finally, intra-MR injections of baclofen
      produced a large increase in dopamine metabolism in the nucleus accumbens and
      striatum but failed to alter hippocampal or striatal serotonin metabolism. These
      findings suggest that baclofen may produce increases in activity and ingestive
      behavior as a result of an action on non-serotonergic cells in the MR.

PMID- 8155297
TI  - Periaqueductal gray lesions do not affect grooming, induced electrically in the
      hypothalamic paraventricular area in the rat.
AB  - Electrical stimulation inducing behavioral responses from the hypothalamus seems
      to activate systems involved in the execution phase of the behaviour rather than
      in the introductory or decision-making phase. However, the pathways involved are
      not fully understood. Projections originating from hypothalamic areas involved in
      specific behavioral responses are rather complex. The periaqueductal gray (PAG)
      has been proposed to be an essential output station of hypothalamic behavioral
      mechanisms. Here we report that lesions of the periaqueductal gray area have no
      effect on grooming responses evoked by electrical stimulation of the hypothalamic
      paraventricular area. Neither threshold current intensities needed to evoke
      grooming, nor latencies were affected 7 or 14 days after lesioning. The lesions
      caused severe behavioural deficits. Animals did not drink or eat spontaneously,
      had problems with motor coordination and sometimes showed strong defensive
      reactions upon touch. However, their grooming responses induced by hypothalamic
      stimulation were not changed. The PAG may have a modulatory role on grooming
      behaviour; however, this modulatory effect apparently is overruled during
      electrical stimulation of the hypothalamus.

PMID- 8155298
TI  - Effects of carbon monoxide on isolated heart muscle cells.
AB  - By sequestering intracellular myoglobin of cardiac muscle cells in the
      nonfunctioning carboxymyoglobin form, carbon monoxide blocks myoglobin
      facilitated diffusion of oxygen, as well as myoglobin-mediated oxidative
      phosphorylation. Here, we explore the hypothesis that the carbon monoxide
      blockade of myoglobin function may be responsible at the cellular level for a
      component of the cardiotoxicity of carbon monoxide observed during exercise.
      Suspensions of isolated rat cardiac myocytes were held in near steady states of
      oxygen pressure near the intracellular partial pressure of oxygen of the working
      heart (2 to 5 torr) and near the end-venous partial pressure of oxygen (20 torr).
      These suspensions were exposed to CO at low pressure (0.07 to 70 torr; 90 to
      90,000 parts per million). The fraction of intracellular carboxymyoglobin,
      determined spectrophotometrically, was in good agreement with the fraction
      predicted from the ratio of carbon monoxide partial pressure to oxygen partial
      pressure. The effects observed were related to the fraction of intracellular
      myoglobin bound to CO. At physiological oxygen pressures no greater than 5 torr,
      after sequestration of approximately 50% of the myoglobin, steady-state oxygen
      uptake decreased significantly and was significantly less than the respiration of
      cell groups for which the fraction of carboxymyoglobin was 0% to 40%. When
      respiration is diminished, the rate of aerobic adenosine triphosphate synthesis
      (oxidative phosphorylation) also decreases. As in the whole heart, cytoplasmic
      adenosine triphosphate concentration in isolated heart cells is controlled at a
      constant level by the creatine phosphokinase equilibrium. When adenosine
      triphosphate utilization is unchanged, a sensitive monitor of the decreased
      adenosine triphosphate synthesis is the ratio of phophocreatine to adenosine
      triphosphate. When carboxymyoglobin was at least 40% of the total intracellular
      myoglobin, we found that the ratio of phosphocreatine to adenosine triphosphate
      in carbon monoxide-treated heart cells was significantly lower than that in
      control cells from the same preparation. Thus, we concluded that sequestering
      intracellular myoglobin as carboxymyoglobin significantly decreased the rate of
      oxidative phosphorylation of isolated cardiac myocytes. We estimate that
      intracellular myoglobin-dependent oxidative phosphorylation will be inhibited
      when approximately 20% to 40% of the arterial hemoglobin in the whole animal is
      carboxyhemoglobin.

PMID- 8155299
TI  - [Quantification of motor activity in biomedicine].
AB  - A computer-assisted analysis of motor activity was carried out using ultrasound
      waves, that are not invasive and free from any kind of interference, because of
      their specific characteristics. We worked out the Doppler's effect which
      determines a frequency variation on the reflected wave from any body in motion.
      That variation is linked to the velocity of the moving body and the
      superimposition of the emitted wave with those reflected, results in beats, which
      have a frequency proportional to the motor activity velocity. Our research group
      planned and carried out an electronic quantification apparatus that can be
      interfaced with a personal computer system by means of an Analog to Digital
      acquisition card. The performed test on the apparatus confirmed that the theory
      that the number of antinodes detected was proportional to the space covered by
      the moving body. The equipment was also tested on several types of animals.

PMID- 8155300
TI  - Endothelium and coronary reactive hyperaemia.
AB  - The effect of the inhibition of the endothelial release of nitric oxide (NO) on
      the hyperaemia which follows a 10 s coronary occlusion was studied in 5
      anaesthetized dogs, keeping aortic blood pressure constant. The left circumflex
      coronary artery was occluded before and after the intracoronary infusion of an
      inhibitor of NO (LNNA). After LNNA, the peak amplitude of the hyperaemia was the
      same but the duration was reduced almost to a half of the control value; it is
      suggested that a myogenic vasodilatation is involved in the amplitude of the
      reactive hyperaemia, while the reduction in the duration of the hyperaemia after
      the inhibitor could result from the shear stress being less effective in causing
      the release of NO during the first part of the hyperaemia.

PMID- 8155301
TI  - [Effect of bisphosphonate on the in vitro proliferation dynamics of CFU-GM].
AB  - Bisphosphonates, potent inhibitors of osteoclast-mediated bone resorption, affect
      different ways of the intracellular metabolism of the osteoclasts. Likewise other
      cell lines are affected by bisphosphonate action, among these the macrophagic
      cells. So we assayed the dichloromethylene diphosphonate (clodronate, Cl2MBP)
      effect on the in vitro proliferation of granulocytic-macrophage progenitor cells
      (GM-progenitors). The bone marrow progenitor cells of four healthy volunteers
      were plated in double layer agar by Pike and Robinson's technique, with the
      addition of clodronate concentrations rising from 0.004 till 4.0 mMol. For each
      experimental point we evaluated: 1) the global growth of the proliferating GM
      progenitors (tPP) deduced from the number of the counted cellular aggregates
      (CA); 2) the mean size (m.s.) of the CA; 3) the total proliferative capacity
      (TPC), deduced from the aggregate mean size per the number of the CA; 4) the
      contribution to the proliferative events by each subsets of proliferating GM
      progenitors (early proliferating GM-progenitors, forming the CA present at the
      7th day of the in vitro culture; later proliferating GM-progenitors, appearing
      only at the 12th day). The dose-effect curve showed decrease both of the tPP and
      TPC for increasing concentrations of clodronate up to a complete growth
      inhibition at the concentration 4.23 mMol of clodronate. Concerning the m.s. of
      the in culture growth aggregates, in three of the four cases it appears unvaried
      up to the Cl2MBP concentration 0.4 mMol. The trends of dose-effect curves have
      been analysed both for colonies (CA-P4) and for clusters (CA-P1, -P2, -P3 of our
      classification).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155302
TI  - Experimental surgical model in osteoporosis study.
AB  - To induce osteoporosis in animals many different experimental models are
      suggested. Experimental animal models play an important role in improving the
      knowledge of the aetiology, pathophysiology, diagnosis, and preventive and
      therapeutical techniques regarding osteoporosis. These experimental models permit
      thorough and standardized data that would be difficult to obtain by experimental
      clinical studies because of the difficulty of evaluating the differences that
      exist among patients. The choice of an in vivo experimental model is conditioned
      by a lot of factors: the reliability, the reproducibility, the feasibility and
      often some factors linked to equipment and costs which are also very important.
      In the present study some experimental models are examined and discussed, and in
      particular an experimental surgical model, that was performed in the Department
      of Experimental Surgery of the Rizzoli Orthopaedic Institute, is described.
      Female Sprague-Dawley rats, 40 or 50 weeks old, 350 +/- 20 g b.w., underwent
      bilateral oophorectomy in order to obtain an oestrogen deficiency. During the
      postoperative period the animals were maintained at the same housing conditions
      and diet. Fourteen days after oophorectomy it was possible to observe an
      osteopenia, that became progressively more pronounced up to 100 days. Till now
      this model permitted the comparative evaluation of different therapeutical
      treatments in such a diffuse and still debated pathology. Many are the
      experimental models adopted for comparative experimental studies of osteoporosis.
      Our model can induce a constant decrease of bone mass both in 50 and in 40 week
      old rats.

PMID- 8155303
TI  - Evaluation of an experimental model of osteoporosis induced in the female rat
      through ovariectomy.
AB  - The present paper intends to check the possibility of improving convenience of
      the osteoporosis model from ovariectomy in the rat by anticipating the operation
      to the 40th week rather than the 52nd week of age, thought by some authors to be
      the optimum model. To this end two parameters have been examined: 1. the bone
      mass variation determined with the vertebral photon densitometer and weighing of
      the femur ashes; 2. the chemico-crystallographic characteristics of the bone
      determined through chemical analysis and X-ray diffractometry. The results
      obtained induce us to believe that ovariectomy carried out on rats of 40 or 52
      weeks of age determine bone mass losses that are statistically comparable. The
      variations in the dry bone weight/ash bone weight ratio are superposable and the
      structural chemical characteristics, due to the increase in bone turnover are
      testified by the increase in osteocalcin. Moreover, it was observed that the most
      reliable evaluation of bone mass loss can be obtained with the vertebral photon
      densitometry. Thus, it is thought that the model which foresees ovariectomy of
      rats 40 weeks after birth compared with those operated 52 weeks after birth,
      represents a good model of osteoporosis from estrogen deficiency which, due to
      the evident practical advantages deriving from the use of younger animals it
      associates a decrease in the use of laboratory animals with statistically
      reliable results.

PMID- 8155304
TI  - Effects of pulsed magnetic fields in the therapy of osteoporosis induced by
      ovariectomy in the rat.
AB  - This paper presents preliminary results on the effects of pulsed electromagnetic
      fields (EMF) in the therapy of post menopausal osteoporosis induced by
      ovariectomy in female rats aged ten months. In particular, the effects of the
      intensity of pulsed EMF applied at constant frequency has been studied. Magnetic
      fields pulsed at 50 Hz were used having a positive sinusoidal wave form with a
      maximum intensity of 30 and 70 Gauss. Treatment lasting one hour per day for 4
      months showed that the pulsed EMF with 30 Gauss of maximum intensity are able to
      slow down the bone mass loss, keeping it within some 10%; with pulsed EMF with 70
      Gauss of maximum intensity, instead, no significant bone mass loss was observed.

PMID- 8155305
TI  - Studies on renal function in healthy women with different degrees of induced
      potassium depletion. 1) Hormonal changes relevant to salt and water balance.
AB  - In healthy women we have studied the effects of potassium depletions of different
      degrees on the generation of some bioregulators of hydro-saline balance. The
      study has been performed on 20 women in normal potassium balance (N group) and 20
      women submitted to potassium depletive treatment by dietary and pharmacological
      means. On the basis of different patterns of treatment we have obtained three
      groups i.e. KD1 (n = 8), KD2 (n = 6) and KD3 (n = 6) with potassium cumulative
      deficit of 160 +/- 43, 198 +/- 22 and 214 +/- 54 mmol, respectively. The renal
      function was assessed by the clearance method during induced hypotonic polyuria
      and subsequent moderate antidiuresis induced by low dose infusion of lysine-8
      vasopressin. The urinary PGE2, 6-keto-PGF1 (6KPGF) and TxB2 were determined by
      the RIA method. Moreover, the basal PRA and urinary aldosterone were determined
      before the renal functional exploration. The data obtained in both KD2 and KD3
      groups where renal hypokalemic dysfunctions occurred--indicate that hypokalemia
      stimulated renin secretion and inhibited the reactivity of renal prostanoid
      production to the polyuric stimulus. However, in the KD3 group--where the
      circulating levels of renin, and probably of angiotensin II were the highest--the
      hypokalemic depression of the synthesis of 6KPGF and TxB2 precursors was
      attenuated while the synthesis of PGE2 was still inhibited.

PMID- 8155306
TI  - [Effects of the inhibition by catecholaminergic and opiatergic pathways of the
      electroencephalographic and vegetative pattern induced by corticotropin-releasing
      factor (CRF) in the rabbit].
AB  - The effects of catecholaminergic and opiatergic transmission inhibitors on CRF
      induced neurophysiological and autonomic patterns were tested. No interactions
      resulted between naloxone and CRF. Both DDC and MPT significantly reduced
      electrocortical and vegetative actions of CRF. Only the bradycardia was
      unmodified after premedications. Therefore our data confirmed the interactions
      between CRF and catecholaminergic pathways. The bradycardic effect seemed
      independent from the "stress-like" syndrome induced by CRF.

PMID- 8155307
TI  - Gas chromatographic detection of class I pesticide residuals in olive oil.
      Preliminary data for a project on food pollution and children's health.
AB  - The data are preliminary findings in order to study the possible pollution of
      fresh olive oil with Class I Pesticides, often misused by olive farmers, and it's
      effect on children's health. The oil produced from the olives of 8 farms in a
      small town of Southern Italy was collected at the mill in 1992, with no previous
      notice to the farmers, and was analyzed by Head Space Gas Chromatographic
      technique. The research for organophosphates and chlorinated pesticides was
      negative. The Kreis test excluded oil rancidity and the index of refraction
      confirmed the oils being fresh olive oil. The fact that the oil samples resulted
      free of pesticide residuals, however, might be explained by the unusual season
      weather not favourable to the olive parasites and the consequent reduced amounts
      of pesticides used by the farmers. The work will be repeated in 1993 and
      completed by a dietary semiquantitative questionnaire and epidemiologic
      evaluations on the children's health.

PMID- 8155308
TI  - [Determination of height from tibia fragments].
AB  - In a study involving the skeletal identification of stature, the Authors have
      performed multiple regression analysis between the measurements taken from 80
      tibias (40 male and 40 female) and the living stature of the subjects to whom the
      tibias belonged to in life. The goal was to allow the forensic investigator to
      estimate the living stature by integral tibias or fragments just using
      association or single tibial measurements. The regression equations obtained
      allow to estimate living stature from different associations of well defined
      segments of tibia. This is a useful aid in forensic investigations, where it may
      be necessary to ascertain the individual's height during his/her life from
      isolated fragmented or mixed skeletal remains.

PMID- 8155309
TI  - [Determination of skeletal sex using discriminant analysis of ulnar
      measurements].
AB  - Twelve ulnar measurements take on a series of 80 skeletons (40 male, 40 female)
      of a known Southern Italian population have been used in 9 combinations to
      produce discriminant functions for skeletal sex determination. The highest
      percentage of correct sex classification (95%) was obtained by the association of
      the minimum circumference and the maximal length. Using other four discriminant
      functions sex is correctly identified in 93.75% of the sample; in addition two of
      these functions, obtained by the associations of: minimum circumference and
      distal epiphyseal breadth, height of proximal articular surface, superior breadth
      and corio-olecranic distance, allowed to have a sex determination even by
      fragmented ulnae. For each discriminant function proposed, coefficients of
      discrimination, section points, male and female centroid and the percentage of
      misclassification are reported. Practical applications of this method will be
      certainly of aid in sexual identification in case of forensic interest.

PMID- 8155310
TI  - Somatosensory evoked potentials by median nerve stimulation recorded with
      cephalic and non-cephalic references. I). Normative study.
AB  - Somatosensory evoked potentials by median nerve stimulation were obtained in 50
      healthy subjects (aged 15-70 years) with cephalic and non cephalic references.
      Most parameters were influenced by one or more independent variables (sex, age,
      arm lengths). The coefficients of the appropriate linear models are reported to
      compute correct individual normal limits.

PMID- 8155311
TI  - Somatosensory evoked potentials by median nerve stimulation recorded with
      cephalic and non-cephalic references. II). Reliability study.
AB  - Reliabilities of parameters of median nerve short-latency somatosensory, evoked
      potential obtained using both cephalic and non-cephalic references was measured
      in 20 healthy volunteers (aged 20-50 years) who repeated the recording session
      after one week. All latency measures and peak-to-peak times were highly reliable;
      amplitudes were less reliable. Upper normal test-retest variability limits of all
      the analyzed parameters were also computed.

PMID- 8155312
TI  - [Correlation between availability of GM progenitors and endogenous CSA production
      in neutropenia].
AB  - We studied some cases with granulopoiesis disorders, owing to different causes,
      all showing peripheral neutropenia. Can these cases benefit by the growth factors
      G-CSF administration? To answer this question we assayed the bone marrow CFU-GM
      growth of the neutropenic patients with standard source of CSA and employing as
      CSA source the autologous peripheral blood mononucleated cells (APBMN). We
      proposed ourselves to investigate the granulopoiesis regulation referring to the
      relation between number of GM-progenitor cells and levels of CSA. The bone marrow
      CFU-GM cultures were performed by Pike and Robinson's double layer agar
      technique. For the evaluation of growth we applied the criterion of the dishes
      topographic lecture according to Ghizzi and De Caro. We plotted the experimental
      data both as absolute count of observed aggregates (tPP) and as dynamic patterns
      of in vitro aggregate proliferation, by differentiating the early proliferative
      events (AC-A and AC-B) from the later ones (AC-C). We observed cases showing
      growths higher under CSA standard source than under autologous source (CAA) and
      vice versa. In other cases there are not noteworthy differences. To estimate
      these growth patterns and to interpret the experimental data we correlated the
      autologous stimulus capacity to the CFU-GM absolute counts. Most cases of
      neutropenia showed inverse correlation between the two indexes. We consider a
      reduced stimulus capacity may be fit when the CFU-GM growth is high. We retain
      this capacity of modulating the CSA production as index of kept regulation of the
      granulopoiesis and, then, these cases can spontaneously evolve towards the
      neutropenia resolution.

PMID- 8155313
TI  - Studies on renal function in healthy women with different degrees of induced
      potassium depletion. 2). Patterns of hypokalemic renal dysfunction.
AB  - In order to investigate the renal functional effects of potassium depletion (KD)
      we have submitted 20 healthy women to different potassium depletive treatments by
      dietary and pharmacological means. By changing these treatments we have obtained
      three KD groups with cumulative potassium deficit of 160 +/- 43 (KD1, n = 8), 198
      +/- 22 (KD2, n = 6) and 214 +/- 54 mmol (KD3, n = 6). Another 20 subjects were
      also studied as controls in normal potassium balance (N group). In all subjects
      the renal function has been evaluated by clearance (cl.) technique both during
      induced hypotonic polyuria and subsequent moderate antidiuresis induced by low
      dose infusion of lysine-8-vasopressin (LVP). A renal dysfunction occurred in
      differences between these two groups, they have been pooled in a single KD2 + KD3
      group. In this group as compared to N the following renal dysfunctions were
      observed during hypotonic polyuria: a) reduction in creatinine cl. (in absence of
      significant differences in mean arterial pressure); b) inhibition of the
      fractional reabsorption of chloride by diluting segments; c) depression of the
      diuretic response to water load. Moreover in KD the LVP was less effective in
      reducing the creatinine cl. while it became effective in reducing the fractional
      excretions of NaCl. These findings indicate that the degree of KD reached in the
      KD2 + KD3 group was adequate to induce a renal dysfunction similar to that
      occurring in conditions of chronic hypokalemia. It is probable that hypokalemia
      by itself along with changes of both prostaglandin and angiotensin renal systems
      are involved in this renal dysfunction.

PMID- 8155314
TI  - Osteoporosis by ovariectomy: calcitonin effect in an experimental model on the
      rat.
AB  - The authors evaluate the efficacy of the aminosuberic derivative of eel
      calcitonin (eCT) in preventing post-ovariectomy osteoporosis in adult rats. The
      drug is administered in a dose of 0.5 U.I./day for four months starting from the
      moment of the ovariectomy. The results show that the treatment is efficacious in
      preventing bone mass loss due to ovariectomy and that the action of the drug does
      not bring about alterations in the normal crystalline structure of the bone.

PMID- 8155315
TI  - Long-term synaptic depression in the mammalian brain.

PMID- 8155316
TI  - Electrical activity and behavior in the pharynx of Caenorhabditis elegans.
AB  - The pharynx of C. elegans, a model system for neural networks and for membrane
      excitability, has been chiefly studied by observing its behavior in normal worms,
      in mutant worms, and in worms lacking pharyngeal neurons. To complement this
      behavioral approach, we devised a method for recording currents produced by
      changes in pharyngeal muscle membrane potential. The electrical records, called
      electropharyngeograms, contain transients caused by pharyngeal muscle action
      potentials and by inhibitory synaptic transmission between pharyngeal neuron M3
      and the muscle. Using the electropharyngeograms, we show that gamma-aminobutyric
      acid is not likely to be the M3 neurotransmitter, that synaptic transmission is
      present but abnormal in mutants lacking synaptotagmin, and that worms mutant in
      the eat-4 gene are defective for M3 function or transmission.

PMID- 8155317
TI  - Periaxin, a novel protein of myelinating Schwann cells with a possible role in
      axonal ensheathment.
AB  - We report the cloning and subcellular localization of a novel Schwann cell
      specific protein of 147 kd that we have named periaxin. Periaxin has a remarkable
      domain of repetitive pentameric units in the primary sequence. It is expressed in
      the first uncompacted whorls of membrane that ensheathe the axon, and further
      synthesis of the protein in the rat sciatic nerve parallels the deposition of
      myelin. In mature myelin, periaxin colocalizes with the myelin-associated
      glycoprotein in the cytoplasm-filled periaxonal regions of the sheath but is
      excluded from compact myelin. We propose that periaxin has a role in axon-glial
      interactions, possibly by interacting with the cytoplasmic domains of integral
      membrane proteins such as myelin-associated glycoprotein in the periaxonal
      regions of the Schwann cell plasma membrane.

PMID- 8155318
TI  - The Schwann cell precursor and its fate: a study of cell death and
      differentiation during gliogenesis in rat embryonic nerves.
AB  - We have characterized a cell, the Schwann cell precursor, that represents a
      distinct intermediate differentiation stage in the process by which Schwann cells
      are generated from neural crest cells. The Schwann cell precursor shows radical
      differences from Schwann cells which include death regulation, antigenic
      phenotype, pattern of cell-cell interaction, migratory behavior, and morphology.
      In the nerves of the rat hind limb, Schwann cells are irreversibly generated from
      these during a brief period, essentially embryonic days 15-17. We also provide
      evidence that the survival of Schwann cell precursors is regulated by neurons and
      identify basic fibroblast growth factor as a potential key regulator of apoptosis
      in Schwann cell precursors and of precursor to Schwann cell conversion. These
      findings have implications for our understanding of gliogenesis in the peripheral
      nervous system.

PMID- 8155319
TI  - A promoterless period gene mediates behavioral rhythmicity and cyclical per
      expression in a restricted subset of the Drosophila nervous system.
AB  - Transgenic flies carrying a 7.2 kb piece of DNA from the period (per) gene were
      analyzed for the presence of circadian locomotor activity rhythms and
      fluctuations of per-encoded mRNA and protein. The 5' end of this genomic fragment
      is within the first intron, which precedes the coding region. This promotorless
      fragment could rescue circadian behavioral rhythms and mediate spatial expression
      of PER in a subset of wild-type per cells within the CNS and PNS. In one
      behaviorally rhythmic line, PER protein was found in only "per lateral neurons."
      In the rhythmic transgenics, per mRNA and protein levels undergo circadian
      cycling, as previously described for wild type. Cycling of PER in brain cells of
      flies carrying the same 7.2 kb piece of per DNA under the control of a heat shock
      promoter corroborated the hypothesis that per's molecular cyclings and behavioral
      rhythmicity are causally related.

PMID- 8155320
TI  - Association of poly(A) mRNA with microtubules in cultured neurons.
AB  - The structural basis for the synthesis of specific proteins within distinct
      intraneuronal compartments is unknown. We studied the distribution of poly(A)
      mRNA within cultured cerebrocortical neurons using high resolution in situ
      hybridization to identify cytoskeletal components that may anchor mRNA. After 1
      day in culture, poly(A) mRNA was distributed throughout all of the initial
      neurites, including the axon-like process. At 4 days in culture, poly(A) mRNA was
      distributed throughout the cell body and dendritic processes, but confined to the
      proximal segment of the axon. Poly(A) mRNA was bound to the cytoskeleton as
      demonstrated by resistance to detergent extraction. Perturbation of microtubules
      with colchicine resulted in a major reduction of dendritic poly(A) mRNA; however,
      this distribution was unaffected by cytochalasin. Ultrastructural in situ
      hybridization revealed that poly(A) mRNA and associated ribosomes were excluded
      from tightly bundled microtubules.

PMID- 8155321
TI  - Cloning and expression of a protein kinase C-regulated chloride channel
      abundantly expressed in rat brain neuronal cells.
AB  - cDNA (CIC-3) encoding a protein kinase C-regulated chloride channel was cloned
      and characterized. The open reading frame encodes 760 amino acids, which possess
      significantly amino acid identity with previously cloned CIC chloride channels.
      The chloride currents expressed in Xenopus oocytes injected with CIC-3 cRNA were
      completely blocked by activation of protein kinase C by 12-O-tetradecanoylphorbol
      13-acetate. Abundant expression of CIC-3 mRNA was observed in rat brain,
      especially in the olfactory bulb, hippocampus, and cerebellum. These findings
      suggest that CIC-3 may play an important role in neuronal cell function through
      regulation of membrane excitability by protein kinase C.

PMID- 8155322
TI  - Participation of multiple calcium channel types in transmission at single
      climbing fiber to Purkinje cell synapses.
AB  - The sensitivity of synaptic transmission to antagonists of different calcium
      channels was examined at the powerful climbing fiber synapse between neurons from
      the inferior olive and cerebellar Purkinje cells. In rat brain slices, climbing
      fibers were activated with extracellular electrodes, and synaptic currents were
      recorded with whole-cell patch clamp. Dihydropyridines did not discernibly affect
      synaptic strength. omega-Conotoxin GVIA, a potent antagonist of N-type calcium
      channels, reduced synaptic currents by an average of 29%. omega-Agatoxin-IVA, a
      high affinity blocker of P-type calcium channels, reduced synaptic strength by an
      average of 77%. Together, the two toxins virtually eliminated synaptic
      transmission (91% inhibition). These results indicate that omega-agatoxin-IVA
      sensitive calcium channels play an important role in transmission at the climbing
      fiber synapse. They also suggest that in single climbing fibers, release is
      evoked by at least two pharmacologically distinct calcium currents, one sensitive
      to omega-agatoxin-IVA, the other to omega-conotoxin GVIA.

PMID- 8155323
TI  - Assembly of mammalian voltage-gated potassium channels: evidence for an important
      role of the first transmembrane segment.
AB  - Three different experimental approaches were used to establish that the first
      transmembrane segment (S1) is important for K+ channel assembly. First,
      hydrodynamic analyses of in vitro translated Kv1.1 N-terminal domain containing
      the S1 segment coassembles to form homotetrameric complexes, whereas deletion of
      the S1 segment abolishes coassembly. Second, coimmunoprecipitation experiments of
      cotranslated Kv1.1 and Kv1.5 truncated polypeptides show that the S1 segment is
      essential for coimmunoprecipitation. Third, dominant negative experiments in
      Xenopus oocytes confirm that over-expression of either the S1 segment or the N
      terminal domain is sufficient for abolishing the expression of functional Kv1.1
      and Kv1.5 K+ channels. These data indicate that S1 segment plays an important
      role in the coassembly of homo- and heterotetrameric K+ channels.

PMID- 8155324
TI  - Positive and negative effects of neurotrophins on the isthmo-optic nucleus in
      chick embryos.
AB  - The survival of neurons in the developing isthmo-optic nucleus (ION) is believed
      to depend on the retrograde transport of trophic molecules from the target, the
      contralateral retina. We now show that ION neurons transport nerve growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3)
      retrogradely and that BDNF and NT-3 support the survival of ION neurons in vivo
      and promote neurite outgrowth in vitro. Surprisingly, NGF enhanced normal
      developmental cell death in vivo in a dose-dependent way. These findings show
      that increased levels of NGF can have adverse effects on differentiated neurons.
      The negative effect of NGF could be mimicked by intraocular injection of
      antibodies that block binding of neurotrophins to the 75 kd neurotrophin receptor
      (p75). These data implicate a role for the p75 receptor in NGF's neurotoxicity
      and indicate that this receptor is involved in the mechanism by which ION neurons
      respond to BDNF and NT-3 in the target.

PMID- 8155325
TI  - Potassium channel inactivation peptide blocks cyclic nucleotide-gated channels by
      binding to the conserved pore domain.
AB  - Cyclic nucleotide-gated (CNG) channels in photoreceptors and olfactory neurons
      are activated by intracellular ligands (cAMP and cGMP) rather than voltage.
      Surprisingly, these channels share amino acid sequence homology with voltage
      gated channels. Here we show that the distinct gating mechanisms exhibited by CNG
      and voltage-gated channels share features that reflect this structural homology.
      Thus, a 20 amino acid peptide ("ball peptide") derived from the Shaker-type K+
      channel and responsible for its rapid inactivation also blocks CNG channels.
      Moreover, the peptide selectively blocks open CNG channels and prevents channel
      closure, showing that CNG channel activation, like activation of voltage
      dependent K+ channels, involves the opening of a gate located on the
      intracellular side of the peptide-binding site. Amino acid substitutions in the
      peptide cause similar changes in blocking affinity of CNG and K+ channels,
      suggesting a conserved binding site. Using a chimeric retinal/olfactory channel,
      we show that the difference in the peptide affinity of the two CNG channels is
      due to a difference in the amino acid sequence of the conserved pore-forming
      region, demonstrating that this domain forms part of the peptide receptor.

PMID- 8155326
TI  - Trk receptors use redundant signal transduction pathways involving SHC and PLC
      gamma 1 to mediate NGF responses.
AB  - In response to NGF, the Trk receptor tyrosine kinase forms a complex with SHC, a
      protein that couples receptor tyrosine kinases to p21ras. Complex formation
      between Trk and SHC, SHC tyrosine phosphorylation, and association of SHC with
      Grb2 were mediated by autophosphorylation at Y490 in Trk [sequence: see text]. To
      determine the role of SHC and other Trk substrates in NGF signaling, Trk
      receptors with mutations in Y490 and Y785 (the PLC-gamma 1 association site) were
      introduced into PC12nnr5 cells. NGF treatment of PC12nnr5 cells expressing Trk
      with mutations in either substrate-binding site resulted in normal neurite
      outgrowth and Erk1 activity and tyrosine phosphorylation. However, PC12nnr5 cells
      expressing Trk with mutations at both sites failed to stably extend neurites and
      efficiently induce Erk1 activity and tyrosine phosphorylation in response to NGF.
      We postulate that Trk receptors can activate Erk1 by either SHC- or PLC-gamma 1
      dependent signaling pathways. These results suggest a model whereby Trk receptors
      utilize at least partially redundant signal transduction pathways to mediate NGF
      responses.

PMID- 8155327
TI  - Quantitative myocardial ultrasonic integrated backscatter measurements during
      contrast injections.
AB  - We and others have shown that normal myocardium exhibits 4 to 5 dB diastolic-to
      systolic cyclic variation (CV) of integrated backscatter. To investigate the
      effect of intramyocardial contrast on integrated backscatter, we injected 5%
      sonicated albumin, containing microbubbles in the range of 5 microns in diameter,
      into the left atrium in nine open-chest dogs. The dogs were anesthetized and
      placed in the right lateral decubitus position on a specially designed table with
      a cutout allowing ultrasound imaging from below. Ultrasonic data was obtained
      from the right precordium by use of a prototype M-mode integrated backscatter
      system implemented in a commercially available two-dimensional system. Usable
      data were obtained in eight of nine dogs. Integrated backscatter increased up to
      13 dB after contrast injections. There was a significantly decreased CV of
      integrated backscatter during myocardial contrast in all eight dogs. The mean
      level of CV of integrated backscatter for the eight dogs decreased from 4.7 dB
      (530 beats analyzed) without contrast to 2.8 dB during contrast (436 beats
      analyzed). There was a trend to greater CV at higher levels of contrast. Septal
      excursion, as measured by M-mode echocardiography simultaneously with integrated
      backscatter by the same ultrasound beam, was similar with and without contrast
      (mean 8.2 vs 8.3 mm). Thus left atrium contrast injection produces quantitatively
      measurable integrated backscatter effects. Cyclic variation of integrated
      backscatter decreases with contrast. However, at higher contrast levels the
      decrease tends to be smaller. These effects should be considered during
      quantitative tissue characterization and myocardial contrast studies.

PMID- 8155328
TI  - Digital formatting standards in medical imaging: a primer for echocardiographers.

PMID- 8155329
TI  - A digital echocardiographic laboratory.

PMID- 8155330
TI  - A new formula for echo-Doppler estimation of right ventricular systolic pressure.
AB  - The Doppler formulas currently used for right ventricular systolic pressure
      (RVSP) evaluation include right ventricular-right atrial (RV-RA) gradient and RA
      pressure. The former is expressed by the velocity of the trans-tricuspid
      regurgitant flow; the latter is generally assumed and is different from one
      formula to another. In 110 patients with cardiac disease with normal or elevated
      pulmonary pressure, we tested a new echo-Doppler formula for the evaluation of
      RVSP based on the estimation of RA pressure by means of the inferior vena cava
      collapsibility index (IVCCI) and compared this method with two traditional
      formulas (methods A and B) and with cardiac catheterization values. Patients were
      classified into three groups on the basis of IVCCI (group 1 > 45%, group 2
      between 35% and 45%, and group 3 < 35%). RVSP was evaluated by method A (RV-RA
      gradient + 10), method B (RV-RA gradient x 1.1 + 14), and our new method, method
      C, which assigns 6, 9, and 16 mmHg to RA pressure in the presence of normal (>
      45%), moderately reduced (between 35% and 45%), or markedly reduced (< 35%)
      IVCCI, respectively. IVCCI correctly identified RA pressure in the three groups
      (group 1, 6.8 mmHg; group 2, 10.8 mm Hg; and group 3, 13.1 mmHg); a high
      correlation existed between Doppler-derived and invasively determined RV-RA
      gradient (r = 0.99). Method C improved noninvasive estimation of RVSP in groups 1
      and 3 compared with the other methods; in group 2, Doppler estimation of RVSP by
      methods A and C were comparable, whereas method B significantly overestimated the
      actual values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155332
TI  - Regurgitant flow of mitral valve prostheses: an intraoperative transesophageal
      echocardiographic study.
AB  - To assess the regurgitant characteristics of mitral biologic and mechanical
      prostheses immediately after implantation, intraoperative transesophageal
      echocardiography was performed in 27 patients, aged 32 to 69 years, undergoing
      open-heart surgery for rheumatic heart disease (n = 19), mitral valve prolapse (n
      = 3), malfunctioning prostheses (n = 3), or periprosthetic leaks (n = 2). The
      prostheses included 13 biologic (Carpentier-Edwards) and 14 mechanical valves
      (five Starr-Edwards, five Medtronic-Hall, and four Bjork-Shiley). Physiologic
      transvalvular regurgitant flow was detected in both biologic and mechanical
      prostheses. The spatial extent of the regurgitant jets was usually greater in the
      mechanical than in the biologic valves, and systolic jets, characteristic of each
      type of valve, were visualized consistently. Trivial periprosthetic jets (PPJs)
      were observed in many implanted valves (14/27). The median maximal jet area was
      0.46 cm2 (range 0.1 to 1.5 cm2). Cardiopulmonary bypass was reinstituted in two
      patients. In one patient a PPJ was judged extensive enough (area 3.6 cm2) to
      warrant surgical revision of the implant, but no dehiscence was found. In the
      other patient a turbulent PPJ (area 5.5 cm2) was associated with a 0.5 cm
      dehiscence at the surgical inspection. In conclusion, (1) all mitral prostheses
      exhibit physiologic transvalvular regurgitation, (2) trivial mitral PPJ is a
      common finding in newly implanted mitral valves and does not require the revision
      of the implant, and (3) further experience based on larger series of patients is
      required to determine the maximal acceptable size of a mitral PPJ detected by
      intraoperative transesophageal echocardiography.

PMID- 8155331
TI  - Septal/free wall curvature ratio: a noninvasive index of pulmonary arterial
      pressure.
AB  - The leftward septal shift, a well-recognized feature of pulmonary hypertension,
      was used to quantify right ventricular pressure in 16 patients with pulmonary
      hypertension and 11 control patients, all with normal left ventricular function.
      Pulmonary pressure was calculated from the tricuspid regurgitation jet and left
      ventricular pressure was taken by arm cuff measurements. Short-axis
      echocardiographic images were obtained and the midwall curvatures of the septum
      and the left ventricular free wall were measured for each frame from end diastole
      to end systole and averaged. The septal/free-wall curvature ratio (CR) was 0.37
      +/- 0.19 in the study group compared with 0.79 +/- 0.06 in the control group (p <
      0.0001). A tight relationship between the CR and the transseptal/transmural
      pressure ratio (CR = 0.057 + 0.89 x transseptal/transmural pressure ratio; r =
      0.98; p < 0.001) was obtained by linear regression. Given the systolic arterial
      pressure, the pulmonary systolic pressure is given by: systolic arterial pressure
      x (1.064-1.12 x CR). Therefore the CR can be used as a noninvasive index that
      reflects the level of pulmonary pressure in relationship to the systolic arterial
      pressure.

PMID- 8155333
TI  - Distinguishing right from left: a standardized technique for fetal
      echocardiography.
AB  - Improved echocardiographic equipment and increasing experience have led to
      accurate and reliable prenatal diagnosis of congenital defects and arrhythmias.
      However, without a standard convention for acquisition and presentation of fetal
      images, distinguishing the right side of the fetus from the left side can be
      difficult and confusing. This article proposes a standard method of image
      acquisition and presentation that allows confident determination of the fetal
      right/left axis by easily identified anatomic landmarks. This technique provides
      a reliable determination of the fetal right/left axis regardless of fetal
      position (i.e., face up, face down, facing left, or facing right), in both real
      time and retrospective review. Only after the fetal right/left axis has been
      determined can accurate diagnoses of fetal atrial and visceral situs, base-apex
      axis, and cardiac segmental anatomy be made.

PMID- 8155334
TI  - Incomplete ventricular septal tear after blunt chest trauma: medical management
      with serial echocardiographic follow-up.
AB  - Incomplete ventricular septal tears are uncommon or probably underreported
      cardiac lesions caused by blunt chest trauma. This report describes two cases of
      incomplete ventricular septal tears that were not suspected clinically.
      Transthoracic and transesophageal echocardiography provided the diagnostic
      information in both of these cases. Despite associated valvular lesions, the
      patients' stable in-hospital course lead to the decision to treat them medically
      with no specific treatment to the incomplete ventricular septal tears.
      Accordingly, these two cases were observed for a mean period of 1.5 years with
      serial echocardiographic studies to track the natural history of these lesions.
      During the follow-up period, both of these cases did not manifest any changes in
      the extent of ventricular septal tear, septal structure, or any left-to-right
      shunting through the tear. There were no significant changes in left ventricular
      size, shape, or systolic function. Thus echocardiographic imaging proved to be
      useful both in initial diagnosis and follow-up.

PMID- 8155335
TI  - Echocardiographic evaluation of the five-chamber heart: a rare congenital
      coronary anomaly.
AB  - Coronary artery fistulas are rare congenital anomalies that usually drain into
      one of the cardiac chambers or veins. The current patient was found to have a
      distinctly unusual anatomic picture, with a fifth cardiac chamber appearing at
      the cardiac apex. This proved to be the drainage site for a large coronary artery
      fistula originating in the left anterior descending coronary artery. The anatomic
      relations and blood flow patterns were demonstrated with transthoracic and
      transesophageal echocardiography.

PMID- 8155336
TI  - Double-chambered left ventricle: submitral accessory valvular tissue causing
      inlet and outlet obstruction.
AB  - We report a patient with a large submitral ridge of muscular and fibrous tissue
      that divides the left ventricle into two distinct chambers causing inlet and
      outlet obstruction. Doppler echocardiography revealed obstruction to both filling
      and ejection. Echocardiography demonstrated that the obstruction was in series
      with the mitral apparatus. Surgery was done with resection of much of this ring
      of tissue. Subsequent studies revealed morphologic and hemodynamic improvement.

PMID- 8155337
TI  - Transesophageal echocardiographic recognition of an unusual complication of
      aortic valve endocarditis.
AB  - Aortic valve endocarditis can cause complications due to involvement of the
      subaortic structures. These complications include satellite vegetations on the
      aortic regurgitant jet lesion sites, involvement of the anterior or posterior
      mitral valve leaflets in the form of aneurysms, perforation, and involvement of
      the mitral-aortic intervalvular fibrosa, namely abscess, aneurysm, and
      perforation into the left atrium or the pericardial sac. These complications can
      be identified accurately by echocardiography. We report an unusual case which
      demonstrates (1) coexistence of both mitral-aortic intervalvular fibrosa and
      mitral valve aneurysms, and (2) echocardiographic follow-up of a mitral valve
      aneurysm to perforation. These complications were recognized by transesophageal
      echocardiography and verified at surgery.

PMID- 8155338
TI  - Papillary muscle rupture caused by bacterial endocarditis: role of
      transesophageal echocardiography.
AB  - A 22-year-old man had severe pulmonary congestion and required mechanical
      ventilation. Endocarditis was suspected because a 2/6 systolic murmur was heard
      at the apex and because Osler nodes were present. Transthoracic and
      transesophageal echocardiography allowed correct diagnosis of papillary muscle
      rupture causing massive mitral regurgitation. To our knowledge, this is the first
      reported case of papillary muscle rupture caused by bacterial endocarditis
      diagnosed by transthoracic and transesophageal echocardiography.

PMID- 8155339
TI  - Aortic dissection without intimal tear: case report and findings on
      transesophageal echocardiography.
AB  - Transesophageal echocardiography (TEE) relies on the presence of an intimal flap
      for diagnosing aortic dissection; however, a small percentage of cases of
      dissection can occur without apparent intimal disruption. This case reviews
      unusual echocardiographic features of aortic dissection and previously
      undescribed echocardiographic findings in a patient with aortic dissection
      without intimal flap.

PMID- 8155340
TI  - Marked diastolic collapse of the right atrium without hemodynamic compromise
      caused by a large pleural effusion.
AB  - A 40-year-old man was seen with a large pleural effusion and marked diastolic
      compression of the right atrium but without physical or other echocardiographic
      signs of cardiac tamponade. The echocardiographic abnormality disappeared after
      thoracentesis.

PMID- 8155341
TI  - Intestinal tamponade: cardiac compression by intestinal contents.
AB  - Intrapericardial herniations represent a rare complication of abdominal or chest
      trauma. We describe clinical tamponade that developed in an elderly patient after
      manual reduction of an umbilical hernia. Echocardiography disclosed loops of
      bowel within the pericardium confirming the clinical diagnosis and leading to
      successful surgical repair.

PMID- 8155342
TI  - Phasic coronary flow characteristics in patients with hypertrophic
      cardiomyopathy: a study by coronary Doppler catheter.
AB  - Abnormal patterns of coronary flow velocity have been observed in patients with
      symmetric left ventricular hypertrophy in conditions such as aortic stenosis and
      systemic hypertension. However, phasic coronary flow characteristics have not
      been investigated in patients with asymmetric left ventricular hypertrophy in
      hypertrophic cardiomyopathy. The purpose of this study was to assess phasic
      coronary flow characteristics and their relation to echocardiographic and
      hemodynamic parameters in patients with hypertrophic cardiomyopathy. Coronary
      flow velocity was recorded in the left anterior descending artery with a 20 MHz
      Doppler catheter in eight patients with hypertrophic nonobstructive
      cardiomyopathy and eight control subjects with normal coronary arteries. Flow
      reversals observed in systole in all patients with hypertrophic cardiomyopathy,
      and the time velocity integrals of systolic flow were significantly smaller in
      patients with hypertrophic cardiomyopathy than in control subjects (-1.5 +/- 1.7
      versus 4.3 +/- 1.2 cm; p < 0.01). The time from the beginning of diastole to peak
      diastolic velocity corrected by the square root of R-R interval (square root of
      RR) was prolonged significantly, and the velocity half-time from peak diastolic
      velocity corrected by square root of RR was shorter in the patients with
      hypertrophic cardiomyopathy compared with those in the control subjects (6.8 +/-
      2.0 msec versus 4.0 +/- 0.6 msec [p < 0.01] and 9.2 +/- 4.9 msec versus 13.9 +/-
      2.0 msec [p < 0.05], respectively). Peak velocity and time velocity integral of
      flow reversal showed significant correlations with anterior ventricular septal
      thickness (y = -0.5x + 13.5, r = 0.8, and p < 0.01; y = -1.3 +/- 16.8, r = 0.8,
      and p = 0.024, respectively), the septal/free wall thickness ratio (y = -0.1x +
      1.1, r = 0.8, and p < 0.01; y = -0.2x + 1.4, r = 0.9, and p < 0.01,
      respectively), and the degree of narrowing of the first septal perforator
      arteries (y = 1.9x + 91.6, r = 0.8, and p = 0.012; y = 6.1x + 80.6, r = 0.9, and
      p < 0.01, respectively). In conclusion, flow reversal in systole and slow
      acceleration and rapid deceleration in diastole were characteristics in patients
      with hypertrophic cardiomyopathy. Flow reversal might be related to the degree of
      left ventricular asymmetry and compression of the septal perforator arteries.

PMID- 8155344
TI  - [The strange lightness of quality...].

PMID- 8155345
TI  - Silent and symptomatic ischemia.

PMID- 8155343
TI  - The history and physical examination of the patient with cardiac disease: a "top
      40" list of diagnostic terms for the cardiac sonographer.

PMID- 8155346
TI  - [Hypertension and well-being: a study with indapamide].
AB  - STUDY OBJECTIVE: Evaluate the clinical efficacy and quality of life of indapamide
      in patients with mild and moderate arterial systemic hypertension under
      indapamide. DESIGN: Open prospective design. SETTING: Outpatient clinics of the
      Instituto Nacional de Cardiologia Preventiva in Lisbon. PATIENTS: Thirty-two
      patients whose supine diastolic blood pressure was between 95 ans 115 mmHg
      without known secondary hypertension, unstable diabetes, cardiac, renal or
      hepatic failure, hypokalemia, coronary artery disease or stroke in the previous
      year. INTERVENTION: After a two week wash-out and four week placebo periods,
      indapamide has been given in a single daily dose of 2.5 mg at breakfast during 12
      weeks. MEASUREMENTS AND MAIN RESULTS: The mean systolic/diastolic blood pressures
      was reduced from 155.7/103.7 to 138.6/86.1 mmHg (p < 0.0001). The mean standing
      systolic/diastolic blood pressure lowered from 160.2/103.7 to 141.6/85.9 mmHg (p
      < 0.0001). The questionnaires on quality of life and the analogic visual scale
      showed a progressive and significant improvement in general well-being. In the
      patient questionnaire the percentage of improvement was 80% (16/20 items) namely
      asthenia, headache, attention, dizziness, tinnitus and visual disturbance. In the
      physician questionnaire all the items improved. Biochemical acceptability was
      characterized by the stability of sodium, chlorine, glucose, creatinine, urea,
      cholesterol, triglycerides, uric acid and slight decrease in potassium from 4.38
      to 4.14 mmol/l (p < 0.01) ranging in normal values. CONCLUSIONS: These results
      confirm the clinical efficacy of indapamide and its beneficial effects on quality
      of life in patients with mild and moderate hypertension when administered in
      monotherapy.

PMID- 8155347
TI  - [Acute myocardial infarct: the prognostic significance of complex coronary
      lesions].
AB  - OBJECTIVE: The aim of our study was to analyze the possible influence of coronary
      lesion morphology on the prognosis of patients (pts) with Acute Myocardial
      Infarction (AMI) evaluated by coronary angiography before hospital discharge.
      DESIGN: Retrospective study. SETTING: Study performed at the Cardiology
      Department of a Central Hospital. MATERIAL AND METHODS: 141 consecutive pts
      admitted because of AMI were evaluated, with an age average of 53.4 +/- 9.6
      years, who had hospital discharge. All pts were submitted to angiography between
      the 2nd and 3rd week after AMI. The ventriculography was evaluated to determine
      the ventricular function score, as defined by the CASS protocol. The
      coronarography was performed to access the number of diseased vessels and to
      analyze their lesion morphology. Complexity was defined by the presence of one of
      the following characteristics: irregularity, shoulder, ulcers, filling defects,
      contrast retention and ecstasy. TWO GROUPS OF PTS WERE CONSIDERED: Group I--n =
      64 pts, with complex lesions, and Group II--n = 69 pts with non complex lesions.
      Seven pts were excluded from the study because they had no significant coronary
      disease. Mean time of the follow up was 21.4 +/- 8.5 months and was similar in
      the two groups. The cardiac events considered were angina after AMI;
      reinfarction; heart failure; new hospital admission, percutaneous transluminal
      coronary angioplasty; coronary artery bypass grafting and death. RESULTS: In
      relation to both groups no statistically significant difference was found
      concerning sex, age, left ventricular function score and number of diseased
      vessels. In group I a higher incidence was found for cardiac events (p 0.006) and
      for the occurrence of angina after AMI (p < 0.02). In this group the number of
      pts with cardiac events was also higher (p < 0.01). No difference was found in
      relation to each of the morphologic characteristics and a high risk profile could
      not be found. CONCLUSIONS: Besides left ventricular function and the number of
      diseased vessels, the analysis of coronary lesion morphology, evaluated 2 to 3
      weeks after AMI, could be useful in risk stratification after AMI.

PMID- 8155348
TI  - [Atrial myxoma. Apropos a clinical case].
AB  - The authors report a case of a 61-years-old woman with hypertension and
      palpitations, who was diagnosed as having a left auricular myxoma. This diagnosis
      was established by echocardiography and confirmed afterwards by an histological
      survey. On the basis of this case the authors reviewed the subject and discuss
      the role of echocardiography in the diagnosis and follow-up of this kind of
      patients.

PMID- 8155349
TI  - [The Ellis-Van Creveld syndrome. Apropos 2 clinical cases].
AB  - The chondroectodermal dysplasia--Ellis-Van Creveld Syndrome--is an unusual form
      of congenital disease, genetically transmitted with a recessive autosomal
      pattern, which involves the skeletal system, nails and teeth. In about 50 to 60
      percent of cases, the affected individuals show cardiac abnormalities, and the
      most common are single atrium, large atrial septal defect, ostium primum type.
      Other abnormalities may accompany these lesions, such as aortic atresia,
      hypoplasia of the ascending aorta or of the left ventricle. About half of the
      patients die in the childhood due to cardiorespiratory complications. Two cases
      are described with this syndrome, a male and a female, with 54 and 45 years old
      respectively; they were followed in our Departments and showed congestive heart
      failure and single atrium. These cases led us to review the subject; we believe
      that the unusual longevity of these patients can be related to their relatively
      benign cardiac disease.

PMID- 8155350
TI  - Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia.
AB  - Catheter ablation using radiofrequency energy became the non-pharmacological
      therapy of first choice for patients with supraventricular tachycardias.
      Modification of the atrioventricular nodal conduction using this source of energy
      can be performed to treat patients with atrioventricular nodal reentrant
      tachycardia. In this article the authors present an updated review of
      radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia
      and report their own experience in this field.

PMID- 8155351
TI  - [Sudden death in athletes].
AB  - Identifying all athletes at risk for exercise-related sudden death is difficult
      because systematic reliable screening is expensive. Nevertheless, if a perfect
      screening method existed, an appreciable number of athletes at increase risk for
      sudden death would not be identified. We think that a careful history designed to
      identify symptomatic athletes and a rigorous family history of congenital heart
      disease may be the most practical screening method.

PMID- 8155352
TI  - [Heart failure and the clinician at the end of the 20th century].
AB  - Congestive heart failure represents a clinical syndrome whose symptoms and signs
      result from different etiopathogenic and pathophysiological mechanisms.
      Diagnosing congestive heart failure remains mainly a matter for accurate clinical
      methodology. Therapeutical approaches to congestive heart failure require a
      profound knowledge of the behaviour of each system and mechanism involved in the
      process, namely neurohumoral activation, dysautonomia and endothelial responses,
      besides renal, skeletal muscle, cardiac and pulmonary participation. So, the
      treatment of congestive heart failure is always multifactorial. Preventing heart
      failure requires also an accurate knowledge of those mechanisms, in order to
      apply the most appropriate measures to stop vascular and cardiac remodeling.

PMID- 8155353
TI  - [Postgraduate cardiology training].

PMID- 8155354
TI  - [Indications and contraindications for intranasal endoscopic and microscopic
      surgery of the nose and sinuses].
AB  - The indications of the pure endoscopic surgery (CEN) and of the combined
      microscopic and endoscopic surgery (MCEN) in naso-sinusal pathology, they are
      established by means of the mixed valuation and systematization of the anamnesis,
      the endoscopy and the computerized tomography (TC). In the anamnesis the
      antecedents will be related carefully in the current history. In the exploration
      will be studied with full particulars the nose and the paranasal sinuses by means
      of the endoscopy and the TC (coronal and axial) with the purpose of valuing
      perfectly the anatomical variations and the sinusal content. The result of it is
      the listing of indications, that which the authors comment the corresponding to
      adults and children. For last the authors commented the absolute and relative
      contraindications.

PMID- 8155355
TI  - [Acoustic distortion products. Recordings from patients with normal hearing and
      those with sensorineural hearing loss].
AB  - Distortion product otoacoustic emissions (DPEs) are a subtype of evoked
      otoacoustic emissions that represent a class of cochlear response. Because of
      their frequency specificity and the wide range of frequencies explored DPEs have
      a great potential for clinical use. DPEs studies include DP-audiograms and
      input/output functions. We recorded 27 DPEs, 24 of them from normal ears and 3
      from pathological ears. This report resumes methods and results.

PMID- 8155357
TI  - [Allergic rhinitis in the region of Merida].
AB  - We studied the whole of 3,047 patients who consult our unit because of a
      presumable allergic affection. The 20% to suffer from allergic rhinitis. The most
      frequent clinical presentation has been rhinitis allergic seasonal followed by
      perennial and to extend seasonal. We have diagnosed through by prick-test,
      specific IgE and ocular provocation test. The ethiology more common has been the
      grass pollen together olive followed pollen grass from seasonal rhinitis. The
      mites dust from perennial rhinitis and the grass and polisensitizations to
      seasonal extend.

PMID- 8155356
TI  - [Myringoplasty using formaldehyde formed fascia (Perkins' foot) in 188 cases:
      anatomical and functional results at 5 years].
AB  - Herein we explain the experiences we have had, in the ORL department of the HCU
      of Valencia, al along a period of seven years, by using the formaldehyde formed
      fascia graft, exposing the anatomical and functional results obtained after a
      minimum pursuit of five years on a sequence of 188 myringoplasties. With such
      method we got to close the tympanic membrane, and that they remain entire after
      five years, on the 72.87% of the cases, getting improvement of audition
      determined by a reduction of the air-bone gap greater than 15 dB, in the 62.77%
      of the cases. Such results are obtained with a very slight number of
      complications. This all makes us to consider this technique as the proper one in
      cases where perforation is greater than 50% of tympanic membrane.

PMID- 8155358
TI  - [Fine-needle puncture-aspiration in the measurement of the DNA content by flow
      cytometry in head and neck tumors. Methodology and applications].
AB  - Fine needle aspiration was used to obtain samples from 15 patients with head and
      neck tumors for posterior analysis of their DNA content by flow cytometry. This
      technique afforded rapid and readily reproducible high quality histograms. A
      review was made of the malignancy criteria according to variations in DNA
      content. Good patient tolerance made it possible to apply the technique
      repeatedly to obtain samples for DNA analysis by flow cytometry, a method of
      great interest in monitoring response to different treatment protocols
      (chemotherapy, radiotherapy).

PMID- 8155359
TI  - [ORL pathology in cystic fibrosis].
AB  - We have studied during 1991 a randomized group of 25 cystic fibrosis children
      whose ages were between 1 and 18 years, analyzing the disease's ENT signs. We
      have found polyps in the 20% of the patients points up for its high incidence,
      and the practical absence of otologic, pharyngeal and laryngeal processes.

PMID- 8155360
TI  - [Application of magnetic resonance to the evaluation of parotid gland diseases].
AB  - The development of magnetic resonance imaging (MRI) during the past few years has
      changed the diagnostic approach to the parotid gland significantly. In the
      present paper the adequate diagnostic management of this area is demonstrated
      while corresponding clinical features are presented simultaneously.

PMID- 8155362
TI  - [Monostotic fibrous dysplasia of the temporal bone coinciding with
      cholesteatoma].
AB  - Fibrous dysplasia is a rare disease which occasionally affects the temporal bone.
      In its monostotic form, only 27 cases have been reported until today. We present
      a case of monostotic fibrous dysplasia of the temporal bone coincident with a
      cholesteatoma of the EAC, operated on by mean of a modified radical
      mastoidectomy, with good results.

PMID- 8155361
TI  - [Late hereditary degenerative sensorineural hearing loss associated with IgA
      mesangial glomerulonephritis of probable autosomal dominant heredity].
AB  - We studied four generations of a Canary Islands family presenting a tardive
      heredodegenerative hearing loss, associated with IgA mesangial
      glomerulonephritis, of probable autosomal dominant heredity. With respect to the
      family, we revised Alport's syndrome, for possible transmission associated with X
      chromosome, as well as heredodegenerative hearing loss associated with renal
      pathology of autosomic transmission currently described; we differentiate these
      hearing losses from our case study, and we discuss the pathogeny of the auditive
      affection in the said hereditary syndromes. Lastly, we stress the autoimmune
      hypothesis because of the IgA nephropathy association in the family case, and we
      list the characteristics of the syndrome described.

PMID- 8155363
TI  - [Chronic sinusitis and nasal polyp as the initial manifestation of cystic
      fibrosis].
AB  - We report the case of a fourteen years old girl suffering from cystic fibrosis of
      pancreas, whose first clinic symptoms were chronic sinusitis and nasal polyp. Her
      most characteristic features were normal height growth without manifestations of
      pancreatic insufficiency or chronic endobronchial infections. Normal spirometry.
      PC 20 histamine > or = 16 mEq/ml. Negative skin test (prick) to common inhalants
      and sweat chloride concentration ranging between 92 and 110 mmol/l.

PMID- 8155364
TI  - [Frontal sinus osteoma associated with intracranial porencephalic cavity].
AB  - A case of an eighteen-year-old student, complaining of frontal and periorbital
      headache is presented. Using conventional radiographies and CT Scan a frontal
      sinus osteoma is diagnosed, finding a hypodense image located in the left frontal
      cerebral lobe, without perilesional oedema or contrast uptake. During the
      surgical act, a destruction of the posterior wall of the left frontal sinus is
      found, penetrating the anterior cerebral fossa and connecting with the cerebral
      cavity in the left frontal cerebral lobe through a fistula of mucosal tissue that
      passes through the dura mater. Complete tumoral exeresis was undertaken as well
      as plastic reconstruction with excellent clinical and cosmetic results. We
      conclude that the early diagnosis and treatment of these benign lesions should be
      undertaken in order to avoid the potential complications they can provoke.

PMID- 8155365
TI  - [Oncocytic cyst of the larynx].
AB  - Oncocytic cysts of the larynx are rare, clinically similar to simple laryngeal
      cysts and a chance find in pathology study. We report a case because of its
      uncommon localization and presentation and we expound different pathogenical
      theories.

PMID- 8155366
TI  - [Tuberculous retropharyngeal abscess in an HIV patient. Report of a case].
AB  - The tubercular retropharyngeal abscess is a rare manifestation of this infection,
      even in the presence of an extensive pulmonary involvement. We present the case
      of a patient HIV positive with an important compromise of the airway, and a
      review of the literature.

PMID- 8155367
TI  - [Cold retropharyngeal abscess associated with cervical vertebral tuberculosis].
AB  - A 38-year-old man, parenteral drug user affected by vertebral tuberculosis with
      involvement of the first, second and third cervical vertebrae associated with a
      cold retropharyngeal abscess is presented. Treatment and main clinical and
      histopathologic features of this very unusual location of tuberculosis are
      discussed.

PMID- 8155368
TI  - Purchasing consumer-focused services.

PMID- 8155369
TI  - Managing markets.
AB  - This paper considers the management of markets in the context of the reformed
      National Health Service (NHS). There are three facets to managing markets:
      regulating and monitoring markets to ensure that they are competent, managing
      contracts, and managing agents. The paper considers issues concerned with market
      structures and entry to and exit from markets; the concept of opportunism is used
      to explore ways in which self-interested behaviour can operate for good or bad in
      the setting up of contracts for health care; and factors related to motivating
      and monitoring agents. The difficulties involved in managing markets are
      reviewed, and Enthoven is criticized for adopting an over-simplified approach to
      market management and the abilities of collective agents. The paper concludes by
      raising questions about the way in which markets are at present being managed in
      the NHS, and the accountability of purchasers for health care provided and the
      money spent.

PMID- 8155370
TI  - Self-perceived health status of hostel residents: use of the SF-36D health survey
      questionnaire. Hanover Project Team.
AB  - As part of a project to assess the health needs of homeless people in Sheffield,
      a survey of hostel residents was undertaken with the aim of measuring self
      perceived health and health service use among respondents. The survey instrument
      incorporated the SF-36D short-form health survey questionnaire. One hundred and
      four (56 per cent) adult hostel residents responded. Respondents reported high
      levels of health service use, and poor average perceived health in comparison
      with the general population. Three-quarters of respondents were identified as
      being at risk of major depressive illness. There was a strong association between
      risk of major depression and recent hospital contact, current use of prescribed
      medication, and low scores on the social function, mental health,
      energy/vitality, pain and general health dimensions of the SF-36. The
      implications of these findings are discussed.

PMID- 8155371
TI  - Reliability of notification data for childhood bacterial meningitis.
AB  - This study reports the notification rates over ten years (1980-1989) for 232
      children with documented bacterial meningitis in Nottingham District Health
      Authority. The average notification rate was approximately 50 per cent of known
      cases. It was higher for meningococcal infections (57/84, 68 per cent) than for
      any other type (45/148, 30 per cent), and lower in neonates (1/29, 3 per cent)
      than in any other age group (101/203, 50 per cent). The results show that the
      notification rates required to be adjusted during the decade of the study (1980
      1989). The achievement of better notification rates may now be more feasible
      since implementation of the recommendations of the Committee of Inquiry into the
      Future Development of the Public Health Function for the control of communicable
      diseases. This paper provides a baseline upon which to measure the impact of such
      changes.

PMID- 8155372
TI  - Suicide in North and West Devon: a comparative study using Coroner's inquest
      records.
AB  - To determine the local characteristics of suicides of North and West Devon
      residents, and to compare them with (a) individuals resident outside the defined
      area but killing themselves within it, and (b) suicides in the remainder of
      England and Wales, a retrospective descriptive three-year review of data from the
      Coroner's confidential inquest records was carried out. The subjects were all
      persons killing themselves within the Coroner's catchment area for North and West
      Devon between 1 January 1988 and 31 December 1990. It was found that persons
      resident outside the area (n = 13) were significantly more likely to be male (p =
      0.007) and have a history of deliberate self-harm (p = 0.03) than Devon residents
      (n = 59). They were also younger (mean age 36.5 years, as opposed to 47.5 years).
      Comparing the Devon residents with the rest of England and Wales, they were
      significantly more likely to die violently (p = 0.017); this was due to the
      increased likelihood of death from firearms (p = 0.016), and to the decreased
      likelihood of death from hanging, strangulation or suffocation (p = 0.02). This
      study highlights the influence that local factors have on the opportunity for
      suicide, such as isolated moorland where cars can be parked (13/72 deaths), or a
      high bridge over a road and river (3/72 deaths) and the ready availability of
      guns in a predominantly rural community (8/72 deaths). In addition, the local
      Coroner's verdict is an important influence on the suicide rate.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155373
TI  - Diagnostic and socio-demographic changes in multiple hospital admission in
      children under two over a five-year period.
AB  - Diagnostic and socio-demographic changes for children experiencing multiple
      hospital admissions (three or more) before the age of two years in two whole-year
      birth cohorts five years apart-1980 and 1985-are reported. The increase in
      multiple admissions between 1980 and 1985 was distributed evenly throughout the
      diagnostic groups. Although a disproportionate increase in admissions per child
      for asthma was noted, the results suggest that the increase accounts for only a
      small proportion of the total increase. A marked trend to earlier age of first
      admission is reported. Low-birthweight infants, infants of young mothers and
      infants from deprived areas of the city are overrepresented in the multiple
      admission groups in both cohorts. There was a marked increase in the proportion
      of low-birthweight infants in the multiple admissions group between 1980 and 1985
      compared with a decrease in the percentage of low-birthweight infants in the
      control group over the same period. The study results are discussed with
      particular reference to the unexplained increase in early childhood admissions.

PMID- 8155374
TI  - Health for All by the year 1990? Progress in Yorkshire.
AB  - In 1985 the World Health Organization proposed 38 health targets towards Health
      for All by the Year 2000, 20 of which were due by the year 1990. A questionnaire
      study was made of progress towards Targets 31-38 in the Yorkshire Health
      Districts. Target 31 (quality of health care) showed fair progress. Trends were
      positive but progress slow on research strategy (Target 32), management support
      (Target 34), health staff training (Target 36) and evaluation of technology
      (Target 38). Little or no progress was discerned on information (Target 35) and
      training of non-health staff (Target 37). Healthy policies at local level are not
      matched by healthy national policies (Target 33), e.g. on tobacco. These
      deficiencies are likely to undermine the development of a national health
      strategy in response to Health of the Nation.

PMID- 8155375
TI  - What's in general practice annual reports?
AB  - All general practices in the United Kingdom are now required to produce an annual
      report. This paper reports on the analysis of reports in one Family Health
      Services Authority's area. The reports varied considerably in content, and many
      of the data were already in the possession of the FHSA for other purposes. The
      reports lack a clear purpose. Little or no information could be gleaned on the
      health of the practice population; in particular, morbidity data were absent from
      the majority of reports. The report mechanism is potentially a useful process,
      but needs to be further developed with the profession to gain maximum benefit
      from the process. The changes in the requirements as a result of the new health
      promotion regulations are a move in the right direction and remedy some of the
      problems identified in this paper, but the role of the annual report still
      remains unclear.

PMID- 8155376
TI  - Comparison of assessments made by a consultant in public health and housing staff
      on applications for rehousing on medical grounds.
AB  - This paper describes a review of a new system introduced in October 1989 for
      rehousing on medical grounds, in which housing staff were primarily responsible
      for making both the assessment and the decision. Part of this review included a
      study to compare points awarded by housing staff with those awarded by a
      consultant in public health. Major discrepancies were found in 11.6 per cent of
      decisions, of which only half were considered potentially to disadvantage
      applicants. On the basis of this review, it was felt that there was justification
      in using non-medical personnel to make decisions on medical priority, with
      medical officers acting in an advisory capacity only. The mechanism for
      processing applications, however, needs careful consideration, as does the
      overall role of medical priority in the allocation of housing.

PMID- 8155377
TI  - The public health physician's role in chemical incidents.
AB  - Chemical incidents such as the methylisocyanate release at Bhopal and the
      aluminium sulphate incident in Lowermoor, Cornwall, are uncommon. However, five
      chemical incidents occurred in Somerset in 12 months between 1990 and 1991, and
      District Health Authorities are required to have plans to deal with such events.
      A survey of the plans held by the Consultants in Communicable Disease Control in
      South Western and Wessex Regional Health Authorities is discussed and the roles
      of public health physicians and emergency organizations are outlined.

PMID- 8155379
TI  - Prospective or retrospective?

PMID- 8155378
TI  - Efficacy of blood screening of donors for antibodies to hepatitis C virus in
      preventing post-transfusion nonA, nonB hepatitis.

PMID- 8155380
TI  - Passive smoking and visits to the general practitioner by schoolchildren.

PMID- 8155381
TI  - Diet in the aetiology of cancer.

PMID- 8155382
TI  - Detection of bone marrow infiltration by neuroblastoma in clinical practice: how
      far have we come?

PMID- 8155383
TI  - Quality assurance of surgery in clinical trials.

PMID- 8155384
TI  - Immunological response to intrathecal and systemic treatment with ganglioside
      antibody R-24 in patients with malignant melanoma.
AB  - Murine monoclonal antibody (MAb) R-24 reacts with the ganglioside GD3 that is
      highly expressed on malignant melanoma. 2 patients with melanosis of the meninges
      received MAb R-24 intrathecally. Regressive changes in tumour cells were observed
      in both patients after intrathecal application of MAb R-24 (1-10 mg, 8-10 h, over
      5-6 weeks). The first patient suffered from brain metastases and died a few weeks
      later, whereas the second achieved a complete remission with no evidence of
      disease 6 years after intrathecal R-24 treatment. No R-24-related neurotoxicity
      has occurred to date. The administration of MAb R-24 caused an increase of
      inflammatory cells in the cerebrospinal fluid (CSF) of both patients. Cytotoxic
      lymphocytes, cultured from the CSF, showed high cytolytic activity against
      allogeneic melanoma cells in vitro. In addition, 15 patients with advanced
      melanoma, in which the brain was not affected, were treated with R-24
      intravenously using high dose R-24 (5 or 10 mg/m2) or low dose R-24 (1 mg/m2). No
      remissions were registered in the high dose group, with only 1/6 patients
      experiencing a mixed response. In contrast, 2/9 patients treated with low dose R
      24 achieved a partial remission, one achieving a minor response and the other a
      mixed response. Toxicity was related to the dose of R-24 administered. Urticaria,
      burning and pruritus were the prominent side-effects, mostly occurring at the
      high dose level. Immunological monitoring during and after intravenous treatment
      showed no significant changes in peripheral blood lymphocytes, natural killer
      cell activity or antibody-dependent cellular cytotoxicity, although transient
      changes were observed. There was no correlation between immunological parameters
      and clinical response.

PMID- 8155385
TI  - Diagnostic and prognostic significance of plasma endotoxin determination in
      febrile patients with haematological malignancies.
AB  - We evaluated the clinical utility of a new endotoxin-specific chromogenic limulus
      test in febrile patients with haematological malignancies. The specificity is
      assured by the removal of factor G, which is sensitive to (1-->3)-beta-D-glucan,
      from horseshoe crab amoebocyte lysate. The sensitivity and specificity of the
      test to systemic gram-negative bacterial infections were 69.7 and 96.3%,
      respectively. Meanwhile, gram-negative bacteria grew in only 39.7% of
      endotoxaemic samples. Thus, it seems appropriate to consider gram-negative
      bacteraemia and endotoxaemia as different entities. Endotoxaemia was
      significantly associated with septic shock and infectious death, especially in
      patients with neutropenia. The new test, the results of which are available
      within 3 h, should help physicians to recognise this ominous sign early and to
      initiate a prompt countermeasure to endotoxaemia.

PMID- 8155386
TI  - Audit of complete axillary dissection in early breast cancer.
AB  - The role of complete axillary dissection (CAD) in the management of breast cancer
      is controversial and largely unresolved. Acceptance of the results of trials
      incorporating CAD assumes that the axillary dissection is truly complete. To
      address this point, and also to define quality control criteria for this
      operation within our unit, we audited 100 consecutive axillary dissections as
      follows: the primary surgeon performed what he/she felt to be a thorough CAD and
      submitted separately the contents of level I, II and III for pathological
      evaluation; a second surgeon then independently assessed the dissection and
      arbitrarily labelled any further excised tissue as level IV. Level IV nodes were
      retrieved in 38% of cases. Tumour involvement of level IV nodes was noted in 5%
      (2/38) of dissections where lymph nodes were retrieved, but in neither instance
      was pathological staging altered. There was a significant decrease in the
      incidence of level IV node retrieval from 47% (28/60) in the first 6 months of
      audit to 20% (8/40) subsequently. This novel approach to our continuing audit
      identified quality control criteria for this procedure in our unit and suggested
      that audit of this kind benefits training.

PMID- 8155387
TI  - Intensive chemotherapy with autologous bone marrow transfusion as primary
      treatment in women with breast cancer and more than five involved axillary lymph
      nodes.
AB  - Patients with breast cancer and a high number of involved axillary lymph nodes
      have a poor prognosis, despite adjuvant chemotherapy. The 5-year disease-free
      survival (DFS) in this group amounts to 30-40% and the 10-year DFS is only 15
      20%. Therefore, new treatment modalities are being sought for this group of
      patients. The aim of the present study was the evaluation of the efficacy of high
      dose chemotherapy combined with autologous bone marrow support. 24 patients with
      a primary breast cancer with more than five involved axillary lymph nodes
      received, after surgery, six courses of induction chemotherapy followed by
      ablative chemotherapy and reinfusion of autologous bone marrow. All patients were
      premenopausal or less than 2 years postmenopausal. Induction chemotherapy
      consisted of methotrexate (MTX) 1.5 g/m2 intravenous (i.v.) and 5-fluorouracil (5
      FU) 1.5 g/m2 i.v. on day 1, prednisone 40 mg/m2 orally on days 2-14, doxorubicin
      50 mg/m2 i.v. and vincristine 1 mg/m2 i.v. on day 14. Courses were repeated six
      times every 4 weeks. 10 patients received cyclophosphamide 7 g/m2 i.v. and
      etoposide 1.5 g/m2 i.v. as intensive regimen, in 14 patients this comprised
      mitoxantrone 50 mg/m2 i.v. and thiotepa 800 mg/m2 i.v. Reinfusion of autologous
      marrow followed on day 7. Finally, patients received locoregional radiotherapy
      for extranodal disease and tamoxifen 40 mg daily orally over a period of 2 years.
      The median age of patients was 42 years, range 29-54. The median number of
      involved nodes was 10. During induction therapy, fever requiring i.v. antibiotics
      occurred in 4% of 144 courses, 14% of patients suffered from mucositis WHO grade
      2-3, and the other patients had mucositis grade 1. During the ablative
      chemotherapy, 1 patient died, 6 developed septicaemia, 5 showed mucositis grade 3
      4 and the other patients had mucositis grade 1 or 2. In the follow-up, 1 patient
      died from acute cardiac failure. Reversible radiation-induced pneumonitis
      occurred in 7 out of 14 irradiated patients; symptoms started directly following
      radiotherapy and lasted for several weeks, but disappeared in due course. During
      follow-up, 2 patients with six and > 10 positive nodes, respectively, have
      relapsed after 18 and 36 months, both in the cyclophosphamide/etoposide regimen.
      Median observation is 3 years, disease-free survival at 5 years is predicted to
      be 84%. Intensive treatment in these patients with high numbers of involved
      axillary lymph nodes is a toxic regimen, but may improve the chance of surviving
      free of disease.

PMID- 8155388
TI  - Influence of toremifene on the endocrine regulation in breast cancer patients.
AB  - In a combined phase I-II study, the hormonal effects of toremifene (TOR) were
      investigated in 30 patients. Half of the patients received continuous therapy of
      TOR 60 mg and half 300 mg of TOR orally daily. Serum concentrations of oestradiol
      (E2), progesterone (PROG), testosterone (TE), follicle stimulating hormone (FSH),
      luteinising hormone (LH), prolactin (PRL), human growth hormone (hGH) and sex
      hormone binding globulin (SHBG) were monitored prior to the treatment and at the
      second, sixth, eighth and twelfth weeks. The influence of TOR upon the
      hypothalamo-hypophyseal axis was investigated by the TRH (thyroid-stimulating
      hormone releasing hormone) functional test using 400 micrograms intravenous
      injection of TRH for stimulation of PRL secretion. The concentration of E2
      decreased during the TOR therapy with 60 mg and 300 mg causing 82 and 71%
      decreases, respectively (non-significant). PRL was significantly (P < 0.001)
      suppressed. Both these effects reflect the anti-oestrogenic action of TOR. SHBG
      increased significantly at both doses of TOR, probably due to a direct oestrogen
      like effect of TOR in the liver. TE decreased as a consequence of the elevated
      SHBG. The TRH-induced PRL release was suppressed by both doses of TOR. There were
      17 and 27% reductions at 12 weeks in the 60 and 300 mg groups, respectively.
      Other hormones measured were not significantly affected by TOR. The hormonal
      effects of 60 and 300 mg doses of TOR did not differ significantly. Anti
      oestrogenic (i.e. decrease of E2), and partially oestrogenic (i.e. increase of
      SHBG) properties as well as the antiprolactinic effects of TOR may have an
      overall beneficial effect in the clinical management of breast cancer patients.

PMID- 8155389
TI  - Phase II trial of oral etoposide plus cisplatin in extensive stage small cell
      carcinoma of the lung: an Eastern Cooperative Oncology Group study.
AB  - Based upon the schedule specificity of etoposide and the in vitro and clinical
      synergy observed with cisplatin, the Eastern Cooperative Oncology Group conducted
      a phase II trial of oral etoposide and cisplatin in newly diagnosed, untreated
      patients with extensive stage small cell carcinoma of the lung. 35 patients
      received 100 mg/m2 of cisplatin intravenously on day 1 and 50 mg/m2 of etoposide
      orally for 21 consecutive days. Cycles were repeated every 28 days. The most
      common toxicity observed was myelosuppression. Sixty-seven per cent of patients
      had grade 3 or 4 leukopenia and 34% had grade 3 or 4 thrombocytopenia during
      cycle one. Of 26 evaluable patients, 4 had a complete response (15%) and 17 had a
      partial response (65%). The median survival for the group as a whole was 8.5
      months. We conclude that this regimen was associated with significant
      myelosuppression, and offered no therapeutic advantage to other commonly
      administered chemotherapeutic regimens for small cell carcinoma of the lung.

PMID- 8155390
TI  - Tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 in patients
      with renal cell carcinoma.
AB  - Patients with renal cell carcinoma (RCC) can exhibit fever, weight loss and
      increases in acute phase proteins. Interleukin (IL)-1, tumour necrosis factor
      (TNF) and IL-6 are considered major mediators of local and systemic inflammation.
      We measured plasma IL-1 beta, TNF-alpha (immunoradiometric assay) and IL-6
      (ELISA) in 78 consecutive patients with untreated RCC and in 56 normal subjects.
      IL-6 plasma levels were higher in patients with RCC (mean 24.2 pg/ml, 11.1-37.3,
      95% confidence interval) than in normal subjects (11.6 pg/ml, 10.1-13.1, n = 39,
      P < 0.01). The patients with fever or weight loss had higher blood levels of IL
      6. IL-6 blood levels were also higher in patients with lymph node invasion and/or
      distant metastases (94.7 pg/ml, 39.0-150.4, n = 15) than in patients with
      undisseminated RCC (7.4, 4.1-10.7, n = 63, P < 0.0001). An abnormal IL-6 plasma
      value (> 40 pg/ml) had a positive predictive value of 91.0% for lymph node and/or
      metastatic spread of RCC. IL-6 was statistically correlated with C-reactive
      protein (nephelometric assay) blood values r' = 0.67, n = 78, P < 0.001). The TNF
      alpha and IL-1 beta levels were not significantly different in patients with or
      without fever or weight loss. The plasma levels of the three cytokines were not
      correlated with the size of the primary tumour. An increased plasma value of IL-6
      is a good marker for tumour dissemination in patients with untreated RCC.

PMID- 8155391
TI  - Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal
      hormone melatonin as a first-line therapy in locally advanced or metastatic
      hepatocellular carcinoma.
AB  - Experimental studies have showed that hepatocellular carcinoma (HCC) cells are
      susceptible to cytolysis of interleukin (IL)-2-activated lymphocytes. Moreover,
      our previous studies demonstrated that the pineal neurohormone melatonin (MLT)
      may enhance IL-2 efficacy. On this basis, a study was started with low-dose IL-2
      (3 million U/day subcutaneously for 6 days/week for 4 weeks) plus MLT (50 mg/day
      orally every day given in the evening) as a first-line therapy of unresectable
      HCC. The study included 14 patients. Objective tumour regressions were obtained
      in 5/14 (36%) patients (one complete response, four partial responses), with a
      median duration of 7+ months. 6 patients had stable disease, while the other 3
      progressed. Toxicity was low in all cases. This study shows that the
      neuroimmunotherapy with low-dose IL-2 plus MLT is a new well-tolerated and
      effective therapy of advanced HCC.

PMID- 8155392
TI  - Genetic linkage in Muir-Torre syndrome to the same chromosomal region as cancer
      family syndrome.
AB  - The Muir-Torre syndrome, in which sebaceous gland tumours occur in association
      with internal malignancy, is inherited as an autosomal dominant disorder. Many
      features of the syndrome are similar to those of the Lynch II cancer family
      syndrome, and thus the two disorders might share a common genetic basis. We typed
      two large families with DNA markers on chromosome 2p around D2S123, a site
      recently shown to be linked to the Lynch II syndrome. LOD scores at this locus
      demonstrated significant and tight linkage to D2S123, suggesting that defects in
      the same gene might give rise to both syndromes.

PMID- 8155393
TI  - Effects of the modulating agent WR2721 on myelotoxicity and antitumour activity
      in carboplatin-treated mice.
AB  - The selective modulation of carboplatin [diammine(1,1-cyclo
      butanedicarboxylato)platinum(II)]-induced myelotoxicity was investigated in mice,
      using the protective agent WR2721 [S-2-(3-aminopropylamino)ethyl-phosphorothioic
      acid, ethiofos]. In female BALB/c mice, WR2721 (200 mg/kg intraperitoneally,
      i.p.) partly prevented the reduction of in vitro proliferation of whole bone
      marrow cells and non-adherent cells when administered at different time points
      relative to 90 mg/kg carboplatin (i.p.). Protection was highest when WR2721 was
      administered 5 min prior to carboplatin. In vitro proliferation of whole bone
      marrow cells and non-adherent cells in liquid culture increased from 15% of
      control for carboplatin alone to 45% when WR2721 was administered 5 min prior to
      carboplatin. However, WR2721 did not significantly prevent the loss in clonogenic
      capacity of early hematopoietic progenitors in the bone marrow, as determined by
      a bilayered soft agar colony forming units assay. In nude mice, bearing well
      established subcutaneous human ovarian carcinoma xenografts OVCAR-3, WR2721 (200
      mg/kg i.p.) 5 min prior to intravenous carboplatin allowed a 1.5-fold increase in
      the maximum tolerated dose of carboplatin as determined by overall weight loss.
      WR2721 alone did not affect tumour growth. However, WR2721 had a potentiating
      effect on the tumour growth inhibition of a standard dose of carboplatin in this
      model. Minimal tumour volume compared to control (T/C) decreased from 9.4% with
      carboplatin alone to 2.2% with WR2721 5 min prior to the same dose of
      carboplatin. Specific growth delay (SGD) increased from 7.4 to 10.3. With the 1.5
      fold increased, equitoxic dose of carboplatin in combination with WR2721, the
      antitumour activity was only slightly further increased (T/C = 1.4%, SGD = 10.5).

PMID- 8155394
TI  - What is the place of carboplatin in paediatric oncology?

PMID- 8155395
TI  - Diet in the aetiology of cancer: a review.

PMID- 8155396
TI  - The EORTC Central Office/Data Center.

PMID- 8155397
TI  - Phase II study of vinblastine and doxorubicin in advanced renal cell carcinoma.

PMID- 8155398
TI  - Complete remission of a primary cutaneous B cell lymphoma treated with
      intralesional recombinant interferon alpha-2a.

PMID- 8155399
TI  - Escape phenomenon after successful bromocriptine and octreotide treatment in
      thyroid stimulating hormone secreting pituitary adenoma residual tissue.

PMID- 8155400
TI  - Mitoxantrone, 5-fluorouracil and levo-leucovorin as salvage treatment in advanced
      breast cancer patients.

PMID- 8155401
TI  - Smoking cessation methods: recommendations for health professionals. Advisory
      Group of the European School of Oncology.
AB  - Smoking is the leading preventable cause of death. Approximately 40% of Europeans
      now smoke. Many smokers want to stop but do not make the attempt, and of those
      who try, most are unsuccessful. Primary care health providers can help their
      patients to stop by using brief behavioural and pharmacological interventions.
      Specialised smoking cessation clinics can support selected patients referred by
      primary care providers. This report reviews intervention techniques for health
      care providers, which, in combination with effective legislative and educational
      interventions, can significantly reduce the prevalence of smoking.

PMID- 8155402
TI  - Factors affecting urinary pyridinoline and deoxypyridinoline excretion in the
      growing lamb.
AB  - Changes in urinary pyridinium crosslink excretion and plasma osteocalcin and
      growth hormone levels were measured at 3-5 week intervals in lambs from 2-22
      weeks of age, in relation to changes in metatarsal length. There were close
      correlations between pyridinium crosslink excretion and plasma growth hormone
      levels and live weight gain, but no direct relationship was seen between the
      rates of excretion of the pyridinium crosslinks and linear bone growth. Plasma
      osteocalcin levels were correlated with linear bone growth rate up to about 12
      weeks of age but, thereafter, showed no correlation despite a continued decline
      in bone growth rate. In the young lamb, daily pyridinium crosslink excretion
      represented 1.3-2.9% of that in the body, declining to 0.06% of pool size in
      adult sheep.

PMID- 8155403
TI  - Effects of menatetrenone on prednisolone-induced bone loss in rats.
AB  - This study was carried out to evaluate the effect of menatetrenone, a vitamin K2
      with 4 isoprene units, on prednisolone-induced bone loss. Three experiments were
      performed in rats which received menatetrenone as a dietary supplement. In
      experiment 1, a soluble form of prednisolone, dissolved in drinking water, was
      administered to rats at 7 mg/kg/day for 9 weeks. The length, dry weight, and bone
      density of femurs and tibiae, as well as urinary gamma-carboxyglutamic acid (Gla)
      content, were significantly lower in the prednisolone-control group than in the
      intact group. Menatetrenone (17 mg/kg/day) significantly inhibited the decrease
      in these bone parameters, especially in tibiae, and completely inhibited the
      decrease in urinary Gla content. In experiments 2 and 3, prednisolone (10 mg/kg),
      dissolved in cottonseed oil, was given to rats intramuscularly three times a week
      for 4 and 10 weeks, respectively. In experiment 2, bone length, bone strength and
      calcium content in the femur were reduced by 4-week prednisolone treatment. These
      reductions were significantly improved by menatetrenone (21 mg/kg/day). In
      experiment 3, 10-week prednisolone treatment reduced bone length and the calcium
      and hydroxyproline content of the femur. Menatetrenone (0.4, 10, and 50
      mg/kg/day) significantly inhibited the reduction of calcium content in the femur.
      These results suggest that menatetrenone may inhibit the bone loss induced by
      corticosteroid treatment.

PMID- 8155404
TI  - Rates of cancellous bone remodeling and turnover in osteopenia associated with
      primary biliary cirrhosis.
AB  - Osteoporosis and fracturing are well-recognized manifestations of primary biliary
      cirrhosis (PBC), but the abnormalities of bone remodeling and turnover that
      result in bone loss are poorly understood. We used dynamic histomorphometric
      techniques to measure tissue level rates of cancellous bone resorption,
      formation, and turnover in 12 premenopausal women with PBC and in 12 normal
      premenopausal women. We compared these values with estimates of bone resorption
      and formation obtained concurrently in the same subjects by radiocalcium kinetics
      and biochemical markers. Rates of bone turnover were analyzed as a function of a
      risk score that reflects the severity of hepatic disease and cholestasis (Mayo
      proportional-hazards model). Positive correlations were observed between tissue
      level and whole skeletal estimates of bone remodeling. At the remodeling site
      (bone multicellular unit [BMU]), the depth of eroded lacunae was unaltered by
      PBC, but wall thickness was decreased. At the level of bone tissues, mean bone
      turnover was increased in PBC patients but varied widely and increased as hepatic
      disease and cholestasis worsened. We conclude that PBC causes a reduction in the
      volume of bone formed at the remodeling site and that the overall level of bone
      remodeling and turnover in PBC is strongly influenced by the severity of hepatic
      disease and cholestasis. We hypothesize that the rate of bone loss in PBC may be
      decreased by therapeutic agents that slow bone turnover, and that further bone
      loss may be halted by liver transplantation.

PMID- 8155405
TI  - Establishment of a rapid bone resorption in vitro assay using previously frozen
      mouse unfractionated bone cells pretreated with parathyroid hormone.
AB  - We established a useful assay system for evaluating osteoclast-mediated bone
      resorption based on the use of unfractionated bone cells obtained from 10- to 11
      day-old mice. When cells from 10 to 11 mice were treated for 7 days with rat
      parathyroid hormone (rPTH, 10(-8) M), a total of 4 to 5 x 10(7) cells could be
      obtained from the culture by treatment with 0.05% trypsin and 0.02% EDTA in PBS.
      These harvested cells contained about 20% tartrate-resistant acid phosphatase
      (TRAP)-positive mononuclear cells. When the harvested cells were cultured on
      dentine slices without rPTH, after 1 day, they formed TRAP-positive multinucleate
      cells that were active in bone resorption. Eel calcitonin (eCT) decreased the
      number of pits in a dose-dependent manner, and its half maximal inhibition dose
      (ID50) was 1.08 x 10(-11) M. Even after having been frozen in liquid nitrogen for
      5 months, upon thawing, these cells were capable for forming pits; and this pit
      formation was inhibited by eCT. Since no appropriate osteoclastic cell line for
      evaluating bone resorption is available at present, this system can provide a
      useful, practical means for assaying osteoclastic bone-resorbing activity.

PMID- 8155406
TI  - Distribution profiles of fluoride in three different kinds of rat bones.
AB  - The study was performed to reveal the detailed distribution profiles of fluoride
      in three different kinds of rat bone--humerus, vertebral arch, and parietal bone-
      and to compare this with the histological appearance of each bone type. Two
      groups of Wistar rats were provided water ad libitum containing 0 and 100 ppm
      fluoride, respectively, for 24 weeks. The fluoride distribution profiles across
      the bone of the three different bones from the outer to the inner surface were
      determined by means of an abrasive micro-sampling technique. In control animals,
      both humerus and parietal bones showed higher concentrations at the periosteal
      and endosteal surfaces, while the vertebral arch showed additional high levels in
      the middle (containing trabecular bone) of the tissue. In exposed animals,
      fluoride levels increased greatly in all three bone types. The vertebral and
      parietal fluoride distribution profiles were relatively unchanged, although
      humerus fluoride increased from periosteum to endosteum. The differences in
      fluoride distribution profiles were apparently related to the histological
      appearances of these bones. The surface area of bone available and the extent of
      vascularity appear to affect fluoride uptake.

PMID- 8155408
TI  - Spectrum of osteoblastic differentiation in new cell lines derived from
      spontaneous murine osteosarcomas.
AB  - Cell lines were established from three spontaneous osteosarcoma and one
      fibrosarcoma of aging mice. They were studied for tumorigenicity, osteoblastic
      features, and other in vitro cellular characteristics, by a combination of
      histological, morphological, biochemical, and molecular approaches. It was found
      that all cell lines formed tumors in vivo, whereas in vitro, only the
      fibrosarcoma-derived cell line grew efficiently in soft agar. Three out of the
      four cell lines produced mouse endogenous retroviruses, but none were classical
      sarcoma viruses. Type I collagen was expressed by all the cell lines, as was
      another extracellular matrix protein, osteonectin. The osteosarcoma-derived cell
      lines, however, exhibited different degrees of osteogenic differentiation. Only
      one line (OSA), and its clonal subline (1G11), consistently gave rise to
      mineralized tumors after transplantation into syngeneic mice, and these cells
      expressed high levels of alkaline phosphatase and bone-specific osteocalcin mRNA
      in vitro. Expression of these biochemical markers of osteoblasts occurred to a
      lesser extent in a second line (OSC) and was undetectable in the third line
      (OSB). The clonal 1G11 cell line exhibits the phenotype of a fully mature
      osteoblast and thus may serve as a particularly useful model for studies of bone
      cell function and regulation. Studies of cells which display a wide spectrum of
      osteogenic potential may further our understanding of the mechanisms involved in
      bone cell differentiation and tumorigenicity.

PMID- 8155407
TI  - A nomogram for predicting lifetime hip fracture risk from radius bone mineral
      density and age.
AB  - A statistical model for predicting a woman's lifetime risk of hip fracture using
      her bone mineral density at menopause has been proposed by Black et al. (1992b).
      We made an additional assumption concerning the correlation of bone mineral
      density between any two ages among postmenopausal women and applied the modified
      model to baseline ages between 50 and 85 years and any bone mineral density level
      likely to be observed in the population. The results are displayed in a form more
      convenient for application of this model in the clinical setting.

PMID- 8155409
TI  - The radiographic trabecular bone pattern during menopause.
AB  - The purpose of this study is to increase the diagnostic value of radiographs by
      observing the radiographic trabecular pattern during occasions of changing three
      dimensional bone structure. We explored how the shape of the radiographic
      trabecular pattern of the distal radius relates to bone mineral density, time,
      and menopausal status. We found that the trabecular pattern correlates with bone
      mineral density and time, especially in the early years of the climacterium.

PMID- 8155410
TI  - Ultrastructural investigations of bone resorptive cells in two types of autosomal
      dominant osteopetrosis.
AB  - In order to investigate the ultrastructure of bone resorptive cells in the two
      types of adult benign human osteopetrosis, iliac crest biopsies were obtained
      from 11 patients and 10 normal males, who served as a control group. Six patients
      had the radiological type I (4 women, 2 men, aged 23-58 years, mean = 36.5
      years), and 5 type II disease (5 men, aged 20-48 years, mean = 29.8 years). The
      normal controls (aged 23-48 years, mean 34.1 years) were recruited from the
      medical staff. The biopsies were immediately divided. From each patients, half
      was embedded in paraffin for histochemistry and light microscopy, and half in
      epon for transmission electron microscopy. The osteoclasts were markedly reduced
      in number and size in Type I disease (0.2 +/- .7 cells vs. 2.9 +/- 1.0 cells per
      2.7 mm2 of bone area, p < 0.01) compared to controls, and stained only weakly for
      tartrate-resistant acid phosphatase (TRAP). At the ultrastructural level, no
      signs of active bone resorption were identified, whereas numerous mononuclear
      cells were observed at the bone surfaces. In type II disease, the osteoclasts
      were large and highly multi-nucleated, with an increased number (8.3 +/- 2.3
      cells vs. 2.9 +/- 1.0. cells per 2.7 mm2 of bone area, p < 0.01) compared to
      controls. In all patients with this type, but never in type I or in the controls,
      a smooth, TRAP-positive substance was seen between the osteoclasts and the bone
      surface. Ultrastructurally, this substance was amorphous, with a condensation
      along the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155412
TI  - Application of confocal laser scanning microscopy to the observation of bone
      biopsy specimens.
AB  - Iliac bone biopsy specimens from five patients with endstage renal disease were
      observed by confocal laser scanning microscopy. Images of affected bone specimens
      were accurately focused, whereas images viewed with conventional light microscopy
      from thick ground sections were obscure. Especially at high magnifications, fine
      structures of bone cells, otherwise blurred, were clearly observed with confocal
      scanning microscopy. From thin-cut sections, images satisfactory for pathological
      diagnosis were viewed with light microscopy even at high magnification. However,
      the sections tended to shrink vertically compared with the cross-sectional images
      of the blocks observed directly by confocal laser scanning microscopy. A three
      dimensional image of bone tissue was also constructed from serial optical
      sections. Confocal laser scanning microscopy is a useful technique for observing
      bone tissues, and may become essential for the evaluation of bone biopsy
      specimens.

PMID- 8155411
TI  - Comparative morphometric changes in rat cortical bone following ovariectomy
      and/or immobilization.
AB  - Gonadal hormone deficiency following ovariectomy and skeletal unloading by limb
      immobilization are useful models of osteopenia. The purpose of this study was to
      compare changes in cortical bone after ovariectomy (OVX) or immobilization (IMM)
      for 6 and 12 weeks. Comparisons were also made when rats were ovariectomized or
      immobilized for 6 weeks and then immobilized (OVX/IMM) and ovariectomized
      (IMM/OVX), respectively, for 6 more weeks. Tibias and femurs were collected and
      static and dynamic cortical bone indices were determined by morphometric methods.
      Femurs from animals OVX or IMM for 12 weeks were tested for bone stiffness by
      torsional testing. Six and 12 weeks after OVX, there were increases in the
      periosteal perimeter, cortical area, and periosteal bone formation indices,
      indicating that ovariectomy increased modeling-dependent bone gain on the
      periosteal envelope, relative to controls. Contrarily, 6 and 12 weeks after IMM,
      there were decreases, compared with controls, in periosteal perimeter, cortical
      bone area, and periosteal bone formation indices. This indicates that
      immobilization decreased modeling-dependent bone gain on the periosteal envelope.
      These differences in modeling between the animals that were OVX and IMM resulted
      in a smaller cortical width and minimum cortical width in the IMM compared with
      the OVX animals. There were significant decreases in cortical bone stiffness and
      minimum cortical width at the fracture site following mechanical testing in the
      animals IMM for 12 weeks. Both ovariectomy and immobilization increased
      endocortical resorption surface, endocortical perimeter and expansion of the
      marrow cavity. Because of suppressed periosteal bone formation with increased
      endocortical resorption, immobilization had a greater effect on bone loss and
      decreased bone stiffness than did ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155413
TI  - [The consumer first .... Interview by Marit Fonn].

PMID- 8155415
TI  - [Travelling solace. Interview by Marit Fonn].

PMID- 8155414
TI  - [Loyalty to the budget--or to the user of health services?].

PMID- 8155416
TI  - [Assistant nurses hit hardest by cutbacks. Interview by Kjell Arne Bakke].

PMID- 8155417
TI  - [Students get involved in Uganda].

PMID- 8155418
TI  - [Blue light for ambulance services].

PMID- 8155419
TI  - [Great differences in quality assurance in Norwegian hospitals].

PMID- 8155420
TI  - [Buskerud psychiatry needs nurses. Interview by Hans C. Faerden].

PMID- 8155421
TI  - [Support for special education. Interview by Hans C. Faerden].

PMID- 8155422
TI  - [He may threaten murder].

PMID- 8155423
TI  - [Manuscript competition: the story of Herman won].

PMID- 8155424
TI  - [A bad start for the newly born. Alcohol-damaged infants--where are they?].

PMID- 8155425
TI  - [A bad start for the newly born. Advocate for the unborn. Interview by Marit
      Fonn].

PMID- 8155426
TI  - How to get relief from being in charge all of the time.

PMID- 8155427
TI  - Bringing CQI to the bedside: a new delivery model.

PMID- 8155428
TI  - A practical model for evaluating new products and technology.

PMID- 8155429
TI  - Nurse leaders share their first class ideas. From classification systems to
      nursing informatics.

PMID- 8155430
TI  - 5'-Azido and 5'-fluoro alpha-nucleosides as analogues of AZT and FLT.
AB  - 5-Azido-2,5-dideoxy-beta-D-erythro-pentofuranosyl nucleosides 10 and their
      corresponding alpha-anomers 11 have been synthesized by condensation of methyl 3
      O-acetyl-5-azido-2,5-dideoxy-beta-D-erythro-pentofuranoside (7) with silylated
      nucleobases followed by deprotection with methanolic ammonia. Reaction of
      silylated thymine (19) with methyl 2,3-di-O-benzoyl-5-deoxy-5-fluoro-D-arabino
      pentofuranoside (15) and methyl 5-azido-2,3-di-O-benzoyl-5-deoxy-alpha-D-arabino
      pentofuranoside (17 alpha) afforded a mixture of the alpha-nucleosides 20 and the
      acyclo nucleosides 5-fluoro- and 5-azido-2,3-O-dibenzoyl-5-deoxy-1-O-methyl-1
      (thymin-1-yl)-D -arabinitol (22). Compounds 20 and 22 were deprotected with
      methanolic ammonia to give the acyclic nucleosides 21 and 23, respectively. The
      new nucleosides were inactive against HSV-1 and HIV-1.

PMID- 8155431
TI  - Facile preparation of 1,6-anhydrohexoses using solvent effects and a catalytic
      amount of a Lewis acid.
AB  - Refluxing solutions of monosaccharides, unprotected at the 6-position and
      carrying O-methyl, S-ethyl, O-acetyl and OH-groups at the anomeric center, in
      acetonitrile containing a catalytic amount of a Lewis acid (O.1-0.4 equiv.)
      yielded 1,6-anhydrohexopyranoses in good to high yields. Best results were
      obtained with methyl 2,3,4-tri-O-dideuteriobenzyl-alpha-D-glycosides (87-91%).
      Dideuteriobenzyl protective groups were used to facilitate NMR spectral
      interpretations.

PMID- 8155432
TI  - Malonofungin: an antifungal aminomalonic acid from Phaeoramularia fusimaculans.
AB  - In screening for antifungal metabolites, a novel compound, malonofungin,
      exhibiting growth inhibitory activity against Botrytis cinerea (grey mould), has
      been isolated from fermentations of Phaeoramularia fusimaculans CBS 616.87. Its
      structure is established as (E)-(3R,4S,5S)-5-acetoxy-2-amino-2-carboxy-3,4
      dihydroxy-14-oxoicos++ +-6-enoic acid, representing an addition to the rare class
      of naturally occurring aminomalonic acids. 1H NMR data and extensive use of CD
      spectroscopy have been utilized to establish the absolute stereochemistry of
      malonofungin. The structural and biological relationship of malonofungin to
      previously reported fungal metabolites is discussed.

PMID- 8155433
TI  - Postoperative pain relief--what is the issue?

PMID- 8155434
TI  - Topical glucocorticoid has no antinociceptive or anti-inflammatory effect in
      thermal injury.
AB  - We have studied the antinociceptive and anti-inflammatory effects of topical
      glucocorticoids in human thermal injury. The right and left legs of 12 healthy
      volunteers were allocated randomly to be treated with either 0.05% clobetasol
      propionate cream or placebo in a double-blind trial. Thermal injuries were
      induced with a thermode, which was heated to 49 degrees C for 5 min under
      standardized pressure. Clobetasol propionate or placebo cream was applied to the
      skin 1 h before burn injury, immediately after the injury and every 12 h for the
      next 3 days. Heat pain detection thresholds (HPDT), heat pain tolerance (HPT),
      mechanical pain detection thresholds (MPDT) and the intensity of burn-induced
      erythema (erythema index, EI) were assessed inside the thermal injury and areas
      of hyperalgesia to pinprick outside the injury were determined before and
      regularly for 72 h after the burn injury. Burn injury caused a decrease in HPDT,
      HPT and MPDT, an increase in EI and development of mechanical, secondary
      hyperalgesia. Clobetasol propionate had no effect on any of the nociceptive or
      inflammatory variables studied.

PMID- 8155435
TI  - Ketoprofen for pain after hip and knee arthroplasty.
AB  - In a double-blind, randomized study, we have compared the effects of i.v.
      ketoprofen 200 mg followed by 12.5 mg h-1 over 13 h, with those of extradural
      morphine 4 mg in 32 patients after hip and knee arthroplasty. A visual analogue
      scale was used to score pain before analgesic administration (first complaint
      after operation), 1 h after and every 2 h subsequently. Pain reduction 1 h after
      the start of analgesia was mean 44% (SEM 17%) in the extradural morphine group
      and 54% (9%) in the ketoprofen group (ns). There were no significant differences
      between groups in pain scores, pain reduction and additional analgesia
      requirement (i.v. paracetamol). Naloxone 5 micrograms kg-1 h-1 was required for
      hypercapnia exceeding 6.0 kPa in three patients in the extradural morphine group
      (vs none in the ketoprofen group; ns). There were no differences between groups
      in side effects, except for urinary retention, which was more frequent in the
      extradural morphine group (P < 0.05). As there were few differences between i.v.
      ketoprofen and extradural morphine, we conclude that ketoprofen may be an
      efficient alternative to extradural morphine after hip and knee arthroplasty.

PMID- 8155436
TI  - Use of two oximeters to investigate a method of movement artefact rejection using
      photoplethysmographic signals.
AB  - Oxygen haemoglobin saturations and plethysmograph signal amplitudes were recorded
      from two oximeters placed on the fingers and toes of 10 patients undergoing
      oesophagectomy, to assess a method of removing motion artefact from saturation
      recordings. By examining changes in the plethysmograph amplitude that preceded
      changes in saturation, episodes of desaturation caused by movement artefacts were
      removed from the data. The reliability of the method was then determined by
      scrutinizing two concurrent oximetric profiles from each patient. A total of 1600
      h of data were evaluated. Desaturations occurring contemporaneously in both
      oxygen saturation profiles were presumed genuine, whereas a desaturation
      occurring in only one of the profiles was classified as artefactual. Our method
      had a sensitivity of 96%, a positive predictive power of 98% and a specificity of
      60%. We modified the method to increase specificity and re-evaluated our data. We
      found that a useful increase in specificity was associated with a considerable
      decline in sensitivity.

PMID- 8155437
TI  - Pre-emptive use of the space blanket reduces shivering after general anaesthesia.
AB  - We have investigated the role of aluminized metal foil (space blanket, UN 320),
      used pre-emptively, in post-anaesthetic shivering and patients' subjective
      perception of cold after general anaesthesia of short duration. Sixty-eight ASA I
      and II patients undergoing orthopaedic and plastic surgery on the peripheries
      were allocated randomly to two groups: those in group 1 were wrapped (not less
      than 60% of body surface area) in the space blanket before induction of
      anaesthesia. In group 2 patients had standard surgical draping. In all subjects,
      anaesthesia was induced with fentanyl and propofol, and maintained with nitrous
      oxide and enflurane in oxygen, after a laryngeal mask airway was positioned.
      Patients were asked to grade their perception of cold on a visual analogue scale,
      before induction and on recovery. Skin (dorsum of hand) and core (nasopharyngeal)
      temperatures were recorded at 15-min intervals. Occurrence of shivering and cold
      scores were recorded by blinded observers. Groups were similar in age and gender;
      duration of anaesthesia was also similar (mean 41.6 (SEM 4.8) vs 47.5 (3.3) min,
      respectively). The incidences of shivering were 15% and 63% in groups 1 and 2,
      respectively (P < 0.001). Cold scores were 2.4 (0.4) and 5.7 (0.5), respectively
      (P < 0.001). Skin temperatures increased with increasing duration of anaesthesia
      in both groups but were greater at 15, 30 and 45 min in group 1 (33.38 (0.25) vs
      31.56 (0.31), 34.46 (0.25) vs 32.45 (0.31) and 35.22 (0.36) vs 33.13 (0.34),
      respectively; P < 0.001 each comparison). Core temperature increased slightly in
      group 1 and decreased in group 2 (P = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155438
TI  - Respiratory sinus arrhythmia: comparison with EEG indices during isoflurane
      anaesthesia at 0.65 and 1.2 MAC.
AB  - Respiratory sinus arrhythmia (RSA) is a cyclical variation in heart rate during
      breathing, where the heart rate increases during inspiration and decreases during
      expiration. RSA and the electroencephalogram (EEG) were monitored in 10 patients
      undergoing elective surgery with isoflurane and nitrous oxide in oxygen
      anaesthesia after induction with propofol. All patients were subject to
      controlled ventilation and recovery from competitive neuromuscular block was
      facilitated by neostigmine and glycopyrronium (seven patients) or atropine (three
      patients). Median and spectral edge (95%) frequencies of the raw EEG were derived
      off-line. RSA and EEG indices were obtained during preinduction (baseline),
      induction, incision, 0.65 and 1.2 MAC of isoflurane maintenance during surgery
      and recovery. Significant decreases in the level of RSA, median and spectral edge
      frequencies were observed during induction and significant increases in all
      indices were observed at recovery in all patients. Significant decreases in the
      median and spectral edge EEG frequencies occurred in patients treated with
      atropine both to counteract bradycardia after propofol induction and at
      antagonism of neuromuscular block (n = 3), compared with patients treated with
      glycopyrronium (n = 7). In contrast, the level of RSA did not decrease
      significantly with atropine. It is concluded that measurements of RSA could form
      the basis of a useful index of anaesthetic depth during isoflurane anaesthesia,
      even during the use of pharmacologically appropriate doses of atropine. However,
      any effects of atropine on the raw EEG and on indices derived from the EEG,
      should be characterized further so that these effects are not confused with
      changes in anaesthetic depth.

PMID- 8155439
TI  - Tracheal intubation without neuromuscular block in children.
AB  - We have studied 80 healthy children, aged 2-14 yr, undergoing adenotonsillectomy
      in a double-blind, randomized design. Tracheal intubation facilitated by either
      suxamethonium 1.5 mg kg-1 or alfentanil 15 micrograms kg-1 was compared after
      induction of anaesthesia with propofol 3-4 mg kg-1. The quality of tracheal
      intubation was graded according to the ease of laryngoscopy, position of the
      vocal cords, coughing, jaw relaxation and movement of limbs. There were no
      significant differences in the overall assessment of intubating conditions
      between the two groups, and all children underwent successful tracheal
      intubation. Fewer patients coughed (P < 0.014) and limb movement was less common
      (P < 0.007) after tracheal intubation facilitated by suxamethonium. Alfentanil
      attenuated the haemodynamic responses to tracheal intubation.

PMID- 8155440
TI  - Influence of muscle temperature and forearm position on evoked electromyography
      in the hand.
AB  - We have examined the correlation between the evoked electromyographic response in
      the first dorsal interosseous muscle of the hand, temperature and forearm
      position in 40 female patients after enflurane anaesthesia with spontaneous
      breathing. In 20 patients the supinated forearm with the wrist extended was
      immobilized on an armboard with adhesive tape (group A). In the other 20 patients
      (group B), the hand was strapped into a fist with adhesive tape and laid supine
      on an armboard. During the 30 min after induction of anaesthesia, the mean
      response to the first stimulus in the train-of-four was the same in both groups
      and decreased from a baseline value of 99.7% (95% confidence interval (CI) 99.1
      100.4%) to 86.2% (95% CI 83.3-89.0%). The final response was less than 90% of
      baseline in 28 patients. There was an inverse linear correlation between the
      electromyographic response and both skin and muscle temperature in both groups (r
      > 0.98), although there was no correlation between change in the electromyogram
      and change in temperature (r < -0.26). After 30 min, pronation of the forearm
      resulted in a further decrease in the electromyographic response in 13 of 18
      patients in group B (two patients in this group were excluded from analysis).
      Pressure was then applied to the scaphoid tubercles of all patients to produce
      maximal supination of the forearm. This had no effect on the electromyogram in 10
      patients. In 28 patients the electromyographic response increased after scaphoid
      pressure, although it remained 90% of baseline in five patients. The measured
      temperatures did not alter during these manoeuvres.

PMID- 8155441
TI  - Monitoring neuromuscular block by acceleromyography: comparison of the Mini
      Accelograph with the Myograph 2000.
AB  - The precision of the compact Mini-Accelograph (M-A) was compared with the
      Myograph 2000 (MYO). Neuromuscular block resulting from atracurium was measured
      simultaneously by the MYO and the M-A applied to contralateral thumbs. During
      onset, the M-A frequently underestimated the extent of block (maximal at
      approximately 50% twitch depression). The M-A control train-of-four (TOF) ratio
      was characteristically > 1.0 and remained greater than the MYO ratio during the
      onset of atracurium. During recovery, the difference between the MYO and the M-A
      was maximal at approximately 50% twitch depression, but the M-A frequently
      overestimated the extent of block. The mean differences between the MYO and the M
      A were small in respect of the recovery index (RI) and the TOF. However, the
      limits of agreement were unacceptably wide for both TOF and RI. When the MYO TOF
      was 0.7, the corresponding M-A TOF varied between 0.4 and 1.0. The M-A was more
      susceptible to drift than the MYO.

PMID- 8155442
TI  - Do infusions of midazolam and propofol pose an infection risk to critically ill
      patients?
AB  - In order to investigate bacterial contamination of i.v. anaesthetic agents, given
      by infusion to critically ill patients, we have cultured residual infusion fluid
      from infusion syringes, 50 containing midazolam and 50 propofol. The infusions
      had been prepared with routine aseptic precautions and had been running for
      between 0.75 and 21.25 h. Only scanty growths of Staphylococcus epidermidis were
      isolated from seven syringes (four midazolam and three propofol). Small volume
      samples were more likely to produce bacterial growth than large volume specimens.
      Midazolam infusions made up in 5% glucose were more likely to be contaminated
      than those made up in 0.9% saline. Antibacterial activity was detected in 18
      midazolam and one propofol filtrate. Midazolam infusions inhibited the growth of
      all seven of the S. epidermidis isolates, whereas propofol supported similar
      rates of multiplication to that obtained with control broth medium. The results
      of this study imply that contamination of the infusions probably occurred after
      they were disconnected from the patient. Despite the ability of propofol to
      support microbial multiplication, we have no evidence to suggest that this is
      clinically significant when infusions are prepared with conventional aseptic
      precautions.

PMID- 8155443
TI  - Haemodynamics of liver reperfusion: comparison of two anaesthetic techniques.
AB  - Reperfusion during liver transplantation is associated with cardiovascular
      instability. We have compared the effects of two anaesthetic techniques on these
      changes. Twenty-six consecutive patients undergoing elective orthotopic liver
      transplantation were anaesthetized using either isoflurane or propofol.
      Haemodynamic profiles were studied before and at specific times after liver graft
      reperfusion. Systemic vascular resistance decreased at reperfusion in both groups
      (P < 0.0001), which was accompanied by increased cardiac output which attenuated
      changes in mean arterial pressure. In the isoflurane group, cardiac output was
      maintained primarily by improvement in stroke volume, whereas in the propofol
      group the increase in stroke volume was less marked and cardiac output was
      maintained by a greater heart rate. The cardiovascular changes were tolerated
      less well in those patients receiving propofol.

PMID- 8155444
TI  - Formation of cytokines by retransfusion of shed whole blood.
AB  - We have studied, in 10 patients undergoing hip replacement surgery, the release
      of cytokines (tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL
      alpha), interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), interleukin-6 (IL
      6) and interleukin-8 (IL-8)) in association with retransfusion of autologous shed
      blood. The patients were reinfused with whole blood collected after operation.
      The median volume returned to the patients was 300 ml whole blood (25-75% range =
      300-425 ml). Before reinfusion, blood was filtered. Plasma concentrations of IL-6
      increased 1 and 60 min after retransfusion (P < 0.05). The plasma concentrations
      of TNF-alpha, IL-1 alpha, IL-1 beta, IL-4 and IL-8 did not change significantly
      after retransfusion of shed wound blood. However, there were increased
      concentrations of IL-1 alpha, IL-1 beta, IL-6 and IL-8 in the collected blood (P
      < 0.001). The filtration procedure did not reduce significantly the
      concentrations of these factors. This study shows that whole blood collected from
      a surgical wound contains large concentrations of cytokines. Filtration of the
      shed wound blood did not reduce significantly these levels and retransfusion
      caused increased plasma concentrations of IL-6.

PMID- 8155445
TI  - Disposition of milrinone in patients after cardiac surgery.
AB  - We have evaluated the disposition of milrinone in seven patients with low cardiac
      output after elective cardiac surgery involving cardiopulmonary bypass. Patients
      received a loading dose of milrinone 50 micrograms kg-1 given over 10 min
      followed immediately by an infusion of 0.5 microgram kg-1 min-1, continued for a
      minimum of 5 h. Plasma concentrations of milrinone were measured at designated
      intervals during the infusion and for 6 h after its termination, by high pressure
      liquid chromatography. Concentrations greater than 100 ng ml-1 were produced in
      all patients within 2 min of starting the loading dose and were maintained for
      the duration of the infusion. Volume of distribution, clearance and terminal half
      life were similar to those found in patients with chronic cardiac failure.

PMID- 8155446
TI  - Comparison of desflurane and fentanyl-based anaesthetic techniques for coronary
      artery bypass surgery.
AB  - We have compared, in 51 ASA II and III patients undergoing coronary artery bypass
      surgery, an inhaled anaesthetic technique based on desflurane, supplemented with
      low-dose (10 micrograms kg-1) fentanyl, with an i.v. technique using high-dose
      (50 micrograms kg-1) fentanyl with midazolam for induction. Satisfactory records
      were available for analysis in 50 patients. There were no differences between
      groups in operating time, cardiopulmonary bypass time, aortic cross-clamp time or
      duration of stay in the intensive care unit after surgery. Desflurane maintained
      mean systemic arterial pressure at the awake level during incision and sternotomy
      (end-tidal concentrations 3.7% and 4.6%, respectively) but decreased it
      significantly at all other times. With fentanyl, mean systemic arterial pressure
      was unchanged from awake values during induction and laryngoscopy but increased
      significantly at incision and sternotomy by 8% and 12.8%, respectively, to exceed
      the desflurane group at sternotomy by 20 mm Hg (P < 0.001). With desflurane,
      heart rate remained at 60-67 beat min-1 at all times before cardiopulmonary
      bypass. This was always lower than the fentanyl group by 5-15 beat min-1 and the
      difference was significant at induction, during skin preparation and before
      aortic cannulation. In comparison with the desflurane group, cardiac index was
      significantly greater in the fentanyl group at induction, laryngoscopy and during
      skin preparation, but was significantly less before aortic cannulation. The need
      for vasodilator intervention was significantly more common in the fentanyl group
      before, during and after cardiopulmonary bypass and for beta adrenoceptor block
      before cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155447
TI  - Oxygen uptake and carbon dioxide elimination during controlled hypotension
      induced by prostaglandin E1 or nitroglycerin.
AB  - To compare the effects of prostaglandin E1 (PGE1) with those of nitroglycerin
      (NTG) on whole body metabolism (oxygen uptake (VO2) and carbon dioxide
      elimination (VCO2) during induced hypotension, we have studied 16 patients
      undergoing elective surgery (radical mastectomy or tympanoplasty). The patients
      were allocated randomly in a non-blinded manner to two groups. Baseline
      characteristics were similar in the two groups. Arterial pressure was controlled
      at about 70% of the baseline value using PGE1 or NTG. VO2, VCO2, gas exchange
      ratio (RQ) and deadspace ventilation ratio (VD/VT) were measured continuously
      with mass spectrometry. The values for all variables were measured for 10 min at
      five times (1 = start of surgery (baseline value); 2 = start of drug infusion; 3
      = 60 min after start of drug infusion; 4 = drug infusion stopped; 5 = surgery
      finished). VO2, VCO2, RQ and VD/VT values were relatively constant in both groups
      during surgery. The balance between oxygen supply and oxygen demand was
      maintained during induced hypotension with PGE1 or NTG.

PMID- 8155448
TI  - Zopiclone as a preoperative night hypnotic: a double-blind comparison with
      temazepam and placebo.
AB  - We have examined the hypnotic effects of zopiclone 7.5 mg and temazepam 20 mg
      compared with placebo in a double-blind, randomized, clinical study of 60
      patients on the night before operation. Evaluation was both subjective (visual
      analogue scales and a sleep questionnaire), to measure the quality of sleep, and
      objective (critical flicker fusion, object recall and paired associates tasks),
      to measure residual impairment. We found that zopiclone was an effective single
      dose hypnotic with similar residual effects to the benzodiazepine and it may
      therefore provide a suitable alternative to benzodiazepines.

PMID- 8155449
TI  - Risk of aspiration with the laryngeal mask.
AB  - In order to assess if the use of the laryngeal mask airway is associated with an
      increased risk of gastric regurgitation during mechanical ventilation, we studied
      50 patients allocated randomly to undergo anaesthesia with either artificial
      ventilation with isoflurane and nitrous oxide in oxygen and atracurium (group A)
      or spontaneous ventilation with isoflurane and nitrous oxide in oxygen (group B).
      In both groups a laryngeal mask airway was used. Regurgitation was assessed by
      the patient ingesting a methylene blue capsule 10 min before induction of
      anaesthesia and examining the oropharynx by direct laryngoscopy at the end of
      surgery. In one patient in each group, there was staining of the oropharynx with
      blue dye at the end of surgery. In the patient in group A, dye was present in the
      trachea and bronchi.

PMID- 8155450
TI  - Continuous infusions of propofol administered to dogs: effects on ICG and
      propofol disposition.
AB  - We have studied the effects of stepwise increasing infusion rates of propofol 200
      500 micrograms kg-1 min-1 on blood concentrations of propofol and the disposition
      and clearance of a bolus dose of indocyanine green (ICG) 0.5 mg kg-1 in 10
      acutely instrumented dogs. Drug concentrations and ICG clearance were measured 30
      min after each change of infusion rate and after reverting for 60 min to the
      basal propofol infusion rate. Increasing infusion rates resulted in significant
      prolongation of the elimination half-life of ICG and decrease in ICG clearance at
      the largest infusion rate (500 micrograms kg-1 min-1) compared with the basal
      rate. Similarly, there were greater than predicted blood concentrations of
      propofol at the largest infusion rate. When the infusion rate reverted to 200
      micrograms kg-1 min-1, and continued for 60 min, there was a significant
      difference between the initial blood concentration of propofol at this basal
      infusion rate and this latter value (P < 0.01). These changes reflect the
      persistent myocardial depression observed during the recovery phase.

PMID- 8155451
TI  - Duration of spinal anaesthesia is determined by the partition coefficient of
      local anaesthetic.
AB  - We have compared the duration of motor block produced by four local anaesthetics
      administered into a chronically implanted subarachnoid catheter in rabbits. Each
      group (n = 6) received four different doses of amethocaine, bupivacaine,
      lignocaine or procaine, and the duration of the resulting motor block was
      assessed. Dose-response curves were plotted for each drug. As a measure of
      activity of the anaesthetics, we used the dose of each drug required to produce
      block of 60-min duration (D60 min) and the correlation between D60 min and
      different drug properties was examined. An inverse linear correlation (r = 0.995;
      P < 0.01) was observed between log D60 min and the log of the partition
      coefficient of the local anaesthetics. No correlation was found between the
      effect and degree of protein binding, pKa or molecular weight. These results
      suggest that, in spinal anaesthesia, the partition coefficient could be used as a
      predictor of the duration of anaesthetic action.

PMID- 8155452
TI  - Influence of droperidol on nausea and vomiting during patient-controlled
      analgesia.
AB  - We have studied the addition of droperidol to morphine during patient-controlled
      analgesia (PCA) in 57 patients using PCA after abdominal hysterectomy. Patients
      in group 1 (control group) received placebo at induction of anaesthesia and a PCA
      containing morphine; those in group 2 received droperidol 1.25 mg and a PCA
      containing morphine and those in group 3 droperidol and a PCA containing
      droperidol 0.05 mg mg-1 of morphine. Patients in the control group suffered 51
      episodes of nausea compared with 35 in the droperidol bolus group and 18 in the
      droperidol PCA group (P < 0.01). In the droperidol PCA group, only 10 doses of
      additional antiemetic therapy were required compared with 24 in the droperidol
      bolus group and 28 in the control group (P < 0.05). We did not observe side
      effects attributable to droperidol. We conclude that droperidol added to morphine
      in PCA reduces nausea and antiemetic requirements after abdominal hysterectomy.

PMID- 8155453
TI  - Video-assisted thoracoscopic placement of paravertebral catheters: a technique
      for postoperative analgesia for bilateral thoracoscopic surgery.
AB  - Paravertebral catheters were placed bilaterally through a Tuohy needle under
      direct video control in a patient undergoing video-assisted thoracoscopic (VAT)
      surgery for recurrent, bilateral pneumothoraces. Postoperative analgesia was
      produced by infusing bupivacaine through the catheters. This provided good
      analgesia. VAT placement of paravertebral catheters is easily accomplished and
      may be a part of the surgical procedure.

PMID- 8155454
TI  - Mivacurium chloride and myasthenia gravis.
AB  - We describe the successful use of the short-acting, non-depolarizing
      neuromuscular blocking agent, mivacurium, in a patient with myasthenia gravis
      taking pyridostigmine 120 mg four times daily. Increased sensitivity to
      mivacurium was demonstrated using train-of-four monitoring. A dose of 0.5 times
      the recommended ED95 (3.0 mg) resulted in 93% block of T1. Spontaneous recovery
      was prolonged with a recovery index (25%-75% T1) of 20.5 min. Residual block was
      antagonized without difficulty using neostigmine 2.5 mg. We discuss the
      relationship between plasma cholinesterase, acetylcholinesterase and
      anticholinesterase drugs.

PMID- 8155455
TI  - The desflurane Tec 6 vaporizer.
AB  - A late development model of the Tec 6 vaporizer for the administration of
      desflurane vapour has been evaluated. It is heated electrically and has both
      electronic monitors of vaporizer function and alarms. The new filling system is a
      significant improvement over previous Tec filling systems. The vaporizer requires
      a warm-up period before it may be used, but when activated it provides an output
      that is approximately linear between 1 and 18% vapour concentrations, at flow
      rates between 200 ml min-1 and 10 litre min-1.

PMID- 8155456
TI  - The desflurane (Tec 6) vaporizer: design, design considerations and performance
      evaluation.
AB  - We have described the design and design considerations of the desflurane Tec 6
      "vaporizer" and have tested its performance characteristics. The vaporizer
      differs from previous vaporizers designed for anaesthesia in that
      electromechanical rather than mechanical controls accommodate the different
      physical characteristics of desflurane. This design, while offering perhaps an
      increased risk of failure (owing to sophisticated electronic components and
      circuitry), on the other hand offers the decreased likelihood of accidental
      delivery of very large concentrations of liquid anaesthetic resulting from
      tilting or overfilling and alarms and warnings not previously incorporated into
      the design of anaesthetic vaporizers. The output characteristics of the vaporizer
      are as expected, based on the design: desflurane concentration output in oxygen
      has accuracy (+/- 15%) which is similar to that of the mechanical vaporizers;
      output decreases when nitrous oxide is added owing to the lower viscosity, but
      remains within 20% of the dial setting or 0.5% absolute.

PMID- 8155457
TI  - Predicting difficult intubation.

PMID- 8155458
TI  - Predicting difficult intubation.

PMID- 8155459
TI  - Can one predict arterial PCO2 from end-tidal PCO2?

PMID- 8155460
TI  - Incidence of aspiration with the laryngeal mask airway.

PMID- 8155461
TI  - Plasma cholinesterase activity in elderly and young adults.

PMID- 8155462
TI  - Alfentanil and propofol for difficult tracheal intubation.

PMID- 8155463
TI  - Alfentanil and propofol for difficult tracheal intubation.

PMID- 8155464
TI  - Prediction of arterial from end-tidal PCO2.

PMID- 8155465
TI  - Magnetic resonance imaging of extradural blood patches.

PMID- 8155466
TI  - Salmonella enteritidis.

PMID- 8155467
TI  - Salmonella enteritidis in Canada.
AB  - During the last few years the prevalence of Salmonella enteritidis in people in
      Canada has increased slightly from 9 to 12% of all Salmonella isolates. Nation
      wide surveys showed a low prevalence of S. enteritidis in poultry flocks: S.
      enteritidis was isolated from environmental samples of 2.7% of layer flocks and
      of 3% of broiler flocks. The overall prevalence of S. enteritidis-contaminated
      eggs from two flocks with infected hens was less than 0.06%. With the exception
      of S. enteritidis phage type (PT) 4, which has not been isolated from poultry in
      Canada, the phage types that occur most commonly in poultry (PT 8, 13 and 13a)
      are also the most prevalent in people. Phage typing was the most effective method
      for subdividing S. enteritidis strains. Eighty-three percent of the S.
      enteritidis isolates from poultry and its environment were sensitive to
      antimicrobial agents. The reasons why strains of the same phage type differ in
      virulence need to be elucidated.

PMID- 8155468
TI  - Understanding Salmonella enteritidis in laying chickens: the contributions of
      experimental infections.
AB  - A significant proportion of human Salmonella enteritidis (SE) outbreaks in recent
      years has been traced to the consumption of contaminated eggs produced by
      infected laying flocks. Experimental SE infections in chickens have been used to
      acquire a considerable amount of basic information about the interaction between
      SE and the avian host. After oral or parenteral inoculation of chickens, SE can
      colonize the intestinal tract, invade and disseminate to reach numerous internal
      organ sites, and elicit the production of specific antibodies in serum and egg
      yolks. Experimental infection of laying hens can result in the deposition of SE
      in the contents of eggs before oviposition, although generally in rather small
      numbers and at a relatively low frequency. The consequences of experimental SE
      infection have been shown to vary significantly with the strain and dose of the
      inoculum. Some SE isolates have been shown to produce various clinical effects,
      including decreased egg production by hens. The information provided by
      experimental SE infections in chickens has played an important role in the
      formulation of appropriate strategies for reducing the incidence of SE in
      commercial laying flocks and thereby also reducing the incidence of transmission
      of SE to consumers via contaminated eggs.

PMID- 8155469
TI  - The socio-economic impact of human Salmonella enteritidis infection.
AB  - Recent government and public concern about the recorded increase in human
      salmonellosis in the UK and abroad has stimulated investigations of both the
      causes and consequences of these infections. This paper discusses the framework
      for economic analysis of food-borne disease and problems associated with the
      estimation of costs. A brief review of the literature in this area is given and
      the results of a national study of the costs of human salmonellosis in England
      and Wales are presented and used to estimate the likely costs of S. enteritidis
      infection.

PMID- 8155470
TI  - Salmonella enteritidis: clinical epidemiological approaches for prevention and
      control of S. enteritidis in poultry production.
AB  - Salmonella enteritidis infections in poultry appear to be of major public
      concern. Prevalence levels in veal calves and pigs are rather low. Because of the
      complex of socio-psychological, welfare, economic and public health aspects great
      emphasis should be put on prevention and control. This paper deals with some
      clinical epidemiological approaches for prevention and control of S. enteritidis.
      Emphasis is set on multifactorial background of infection occurrence,
      epidemiological methods and features of monitoring and surveillance for
      evaluation of measures taken during a follow-up period. Finally, it is stated
      that the application of Risk Assessment & Analysis principles in this problem
      area, integrating the concepts previously addressed, might prove to be a valuable
      perspective.

PMID- 8155471
TI  - Intervention strategies for Salmonella enteritidis in poultry flocks: a basic
      approach.
AB  - Poultry laying flocks can become infected with Salmonella enteritidis by several
      routes. In this study a model is presented of the cumulative infection curve of
      S. enteritidis in laying flocks. Based on this model and practical results the
      contribution of different routes to the infection can be estimated providing a
      basis for an effective intervention strategy. For illustration, the cumulative
      infection curve of S. enteritidis in Dutch laying flocks is analysed. This curve
      shows a low level of infection at the start of the laying period which indicates
      that the contribution of the vertical infection route (from infected breeding
      flocks to progeny) is small. The course of the infection curve indicates that
      there is a high probability of infection in the first part of the laying period.
      The result suggests that the laying flocks become infected mainly from the farm
      environment including not properly cleaned and disinfected poultry houses and
      infected vermin present on the farm. As a consequence, intervention in The
      Netherlands should be directed to trace S. enteritidis-contaminated laying farms
      and eradicate the contamination.

PMID- 8155472
TI  - Salmonella enteritidis in Argentina.
AB  - A significant increase in the number of isolations of Salmonella enteritidis has
      been observed in Argentina since 1986. Outbreaks of foodborne diseases in humans
      were associated with the consumption of raw or undercooked hens' eggs. Between
      1986 and the first 6 months of 1993 there were 150 outbreaks reported, affecting
      more than 6000 persons. A total of 71.3% of these outbreaks were confirmed by
      stool cultures, and 47.3% by bacteriological study of the food implicated in the
      outbreak. A permanent surveillance of salmonellosis is imperative, taking into
      account the persistence of Salmonella enteritidis isolations in sporadic cases
      and in new outbreaks.

PMID- 8155473
TI  - Salmonella enteritidis control programs in the United States.
AB  - A sharply rising incidence of salmonellosis in humans caused by Salmonella
      enteritidis (SE) in the United States between 1985 and 1989 resulted in a
      government-sponsored outbreak traceback program which was started in 1990. Layer
      flocks considered the sources of egg-implicated outbreaks would be tested for SE
      and the eggs from these flocks would be diverted to pasteurization plants. A
      program to eliminate SE from primary and multiplier breeding flocks was started
      at the same time. A subsequent spent hen survey and a survey of prepasteurized
      liquid egg material revealed that SE was much more prevalent than had been
      suspected, and that the highest prevalence was found in the northeastern and
      middle Atlantic states. Since the SE rates did not decrease during the next 2
      years, a pilot project was started in 1992 in Pennsylvania, in one of the most
      highly affected areas. The project was designed to reduce the number of SE
      outbreaks by diverting eggs from SE-affected flocks and at the same time
      attempting to delineate the epidemiology and control aspects of the disease. With
      the results generated during the fist 18 months of the Pilot Project, a much
      larger SE prevention program will start in the same area, in October 1993.

PMID- 8155474
TI  - Salmonella enteritidis eradication programme in poultry breeder flocks in The
      Netherlands.
AB  - Results of a Salmonella enteritidis eradication programme in poultry breeder
      flocks in The Netherlands in 1989-1992 are presented. A top-down approach was
      performed, which means if infection is cleared out from the top end (breeding
      stock), and good hygiene standards are maintained throughout the industry, the
      infection will be progressively cleared from the whole of the national stock.
      Each year all poultry breeder flocks (approx. 2300) were screened for the
      presence of S. enteritidis by bacteriological examination of caecal droppings
      until 1 April 1992. After that date, screening was carried out with a 'double
      antibody sandwich blocking' (DAS blocking) ELISA-method. Treatment of S.
      enteritidis-positive flocks, even in production, with Baytril (enrofloxacin) and
      competitive exclusion flora turned out to be a good alternative for slaughtering
      these flocks. The top-down approach seems to be successful also in relation to S.
      enteritidis infection in humans in The Netherlands, since no further increase of
      human infections has been observed during the last 3 years.

PMID- 8155475
TI  - The epidemiological situation of Salmonella enteritidis in Poland.
AB  - The epidemiological situation connected with S. enteritidis in Poland, in the
      years 1961-1991, is described. During this period there were two increases in
      infections and food poisonings, which were of an epidemiological character. The
      first epidemic, in 1962-1976, affected primarily small children and spread by
      contact in a hospital environment. It caused serious diseases, or dangerous
      complications in already existing illnesses, with high mortality. A few foci of
      later food poisonings were caused by infected meat or meat by-products. The
      second epidemic, which began in 1980 or 1981 and still exists, has already
      affected about 500,000 persons. It has often concerned cases of sporadic
      infections, mainly in the case of small children, but it has not been of a
      hospital epidemic character. It has been far more frequently associated with food
      poisoning outbreaks caused by contaminated ice-cream, cream cakes, eggs,
      mayonnaise and, less frequently, by meat and meat by-products. Attention is drawn
      to the large number of humans transmitting S. enteritidis infections in Poland.

PMID- 8155476
TI  - Contamination of egg shell and contents with Salmonella enteritidis: a review.
AB  - Salmonella enteritidis can contaminate the contents of clean, intact shell eggs
      as a result of infections of the reproductive tissue of laying hens. The
      principal site of infection would appear to be the upper oviduct. In egg contents
      the most important sites of contamination are either the outside of the vitelline
      membrane or the albumen surrounding it. In fresh eggs, only few salmonellas are
      present and as albumen is an iron-restricted environment, growth will only occur
      once storage-related changes to vitelline membrane permeability, which allow
      salmonellas to invade yolk contents, have taken place. When this happens high
      populations are achieved in both yolk contents and albumen. Some eggs from
      naturally infected hens have been found to contain large numbers of S.
      enteritidis. The rate of change in membrane permeability is temperature
      dependent. In eggs stored at 20 degrees C, yolk invasion is uncommon until eggs
      have been stored for 3 weeks. In stimulated kitchen conditions where temperatures
      reached 30 degrees C, salmonellas could grow rapidly after a few days.

PMID- 8155477
TI  - Conventional methods for the detection and isolation of Salmonella enteritidis.
AB  - Conventional methods for the specific isolation of Salmonella enteritidis are
      scarce. For pre-enrichment, addition of ammonium-iron (III)-citrate, ferrioxamine
      E and G or novobiocin in combination with cefsoludin to Buffered Peptone Water
      (BPW) and of ferrous sulphate to Trypticase Soy Broth seems to favour S.
      enteritidis isolation. As far as selective media are concerned, the use of semi
      solid media, and addition of nitrofurantoin, results in higher isolation rates of
      the S. enteritidis serovar. Addition of 0.0015% nitrofurantoin to semi-solid
      DIASALM is so far the only successful combination reported. Addition of 0.0015%
      nitrofurantoin to solid media, in this case to XLD, is also reported. Use of a
      semi-solid medium, preferably DIASALM + 0.0015% nitrofurantoin, in addition to
      the selective media routinely used is recommended.

PMID- 8155478
TI  - The use of latex particle agglutination to specifically detect Salmonella
      enteritidis.
AB  - This paper reviews the development and evaluation of a latex particle
      agglutination test to specifically identify cultured Salmonella enteritidis
      organisms. The test is based on the use of two monoclonal antibody-coated latex
      reagents, one of which detects the recently discovered SEF14 fimbriae expressed
      predominantly by S. enteritidis and S. dublin organisms, while the second reagent
      detects the H'p' antigen of S. dublin flagella. In a series of field trials 141
      out of 142 strains of S. enteritidis from eighteen phage types were correctly
      identified by the latex test. A further 175 salmonella isolates representing 35
      serotypes were tested and only two false-positives (S. dublin) in the latex test
      were recorded. This is the first rapid serotype specific test for S. enteritidis
      to be developed, and highlights the potential advantage of fimbrial antigens as
      novel diagnostic antigens of the future.

PMID- 8155479
TI  - Serological diagnosis of Salmonella serotype enteritidis infections in poultry by
      ELISA and other tests.
AB  - Serological methods have increasingly been used for the detection of invasive
      Salmonella serotypes including enteritidis in poultry. Different types of ELISA,
      particularly indirect or double antibody-blocking assays using a variety of
      antigens such as lipopolysaccharide, flagella and SEF14 fimbrial antigen are used
      as part of control programmes in a number of countries. There are many advantages
      to using such assays for preliminary screening of flocks prior to using
      bacteriological culture methods.

PMID- 8155480
TI  - Salmonella enteritidis in Italy.
AB  - During the period 1982-1992 the percentages of Salmonella enteritidis isolations
      in Italy have increased from 2.4 to 57.1% from human beings and from 0.5 to 22.8%
      from food. Seven hundred and fifty-seven isolates, 702 from man and 55 from food,
      were characterized. Phage type 4 accounted for the 76.8% of these isolates. The
      majority of strains were sensitive to the antibiotics tested; only 18 (2.4%)
      showed resistance to three or more antibiotics by nine different patterns.

PMID- 8155481
TI  - Pathogenicity of Salmonella enteritidis in poultry.
AB  - Salmonella enteritidis is a common pathogen of all species of mammals and fowls.
      The recent increase in the number of outbreaks of food poisoning due to S.
      enteritidis in man was epidemiologically analysed, and it was considered that
      contaminated eggs or egg products were the major source of this infection. To
      assist in prevention and eradication of human food poisoning many investigators
      have studied the pathogenicity of S. enteritidis in poultry. Gross pathological
      observations after natural and experimental infections with S. enteritidis in
      poultry revealed that this organism may cause systemic infection in chicks and
      laying hens accompanied by prolonged faecal shedding. Some variations in the
      mortality rates, clinical symptoms, faecal shedding and frequency of production
      of contaminated eggs were observed in the chicks and hens experimentally infected
      with S. enteritidis isolates. Choice of bacterial strain, phage type, age of bird
      and inoculum size may affect the outcome of an infection. Moreover, isolation of
      the organisms from the ovaries, oviducts and egg contents indicates the
      possibility of transovarian infection of S. enteritidis in chickens. Some
      virulence factors associated with S. enteritidis are also reviewed in the present
      paper.

PMID- 8155482
TI  - Further study on the magnesium-mediated change in physical state of phospholipid
      modulates mitochondrial F0-F1-ATPase activity.
AB  - We have postulated that magnesium may play a role in altering the lipid fluidity
      of the bilayers, which would induce a change of conformation of the F0-ATPase
      portion (buried in the lipid core) of mitochondrial F0-F1-ATPase. Such change
      could be transmitted to the soluble F1 portion, resulting in higher enzymatic
      activity. The assumption was further supported by the results presented in the
      following: (1) A conformational difference for the F0-ATPase-containing
      proteoliposomes induced by the magnesium effect could be detected using a
      fluorescent probe acrylodan; (2) H(+)-translocation activity of F0-ATPase
      incorporated proteoliposomes with magnesium, monitoring by fluorescence quenching
      of 9-aminoacridine or the bulk phase pH change, was higher than that without
      magnesium; (3) The magnesium effect on the reconstituted F0-F1-ATPase activity
      was greatly enhanced when the reconstitution was carried out in the presence of
      oligomycin sensitivity conferring protein (OSCP, a main component of the
      connecting link between the F1 and F0 sector of F0-F1-ATPase).

PMID- 8155483
TI  - Magnesium effect on the membrane potential of smooth muscle cells of human
      placental chorionic vessels.
AB  - The effects of magnesium ions were studied in human placental chorionic vessel
      smooth muscle cells (from arteries and veins), particularly on the membrane
      potential Um. Um was classically recorded with microelectrodes. Magnesium ions,
      in the range 1-10 mM, depolarize the membrane of the smooth muscle cells (the
      effect is more important in arteries than in veins). Magnesium ions influence the
      membrane potential directly and regulate the viability of the K+ channels.

PMID- 8155484
TI  - A magnesium-deficient high fructose diet augments bone-sparing action of
      exogenous oestrogen in ovariectomized rats.
AB  - To investigate interactions between circulating oestrogen, high dietary fructose,
      and low dietary magnesium on bone mineral density and numbers of trabeculae, 10
      week old ovariectomized (OVX) and sham-ovariectomized (SOVX) rats were studied.
      The OVX animals were divided into three groups: one-third of the animals were
      injected with beta-oestradiol-3-benzoate dissolved in sesame oil twice a week;
      another one-third were injected with testosterone cypionate; and the remaining
      OVX and all of the SOVX animals were injected with sesame oil only. One-half of
      the animals in each group were fed cornstarch without magnesium and the other
      half, fructose without magnesium. After a 14 week experimental period, a 24 h
      urine sample was collected for measurements of Ca, Mg, P and cAMP. Blood was
      collected for determination of Ca, Mg, P, 25-hydroxy- and 1,25-dihydroxy
      cholecalciferol. Femurs were used for determination of bone density, and tibiae
      for numbers of trabeculae. Testosterone-treated and OVX control animals fed
      cornstarch diets had the lowest bone density, whereas oestrogen-treated and SOVX
      control rats fed fructose had the greatest bone density. Oestrogen-treated
      animals fed fructose without magnesium had the highest serum and urinary Ca,
      whereas testosterone-treated animals fed cornstarch without magnesium had the
      lowest serum and urinary Ca. Serum alkaline phosphatase was higher in OVX- and
      testosterone-treated and starch-fed animals as compared to their respective
      counterparts. High urinary cAMP in OVX- and testosterone-treated animals may
      reflect the action of increased circulating concentrations of PTH, which could be
      responsible for bone resorption. The results show that high dietary fructose
      without magnesium interacts with endogenous or exogenous oestrogen to decrease
      bone mineral loss significantly in ovariectomized rats.

PMID- 8155485
TI  - Magnesium inhibition of carbachol-induced contractions of the rat uterus and
      gastrointestinal tract: ex vivo effect of long term streptozotocin-induced
      diabetes.
AB  - Rats were rendered diabetic by a single administration of streptozotocin (STZ).
      They were maintained in the diabetic state for six weeks before being killed, and
      diabetic state was confirmed by routine urine and blood glucose estimations. The
      contractile sensitivity of jejunum, colon, stomach fundus and uterus to carbachol
      was reduced in control animals by increasing buffer magnesium concentration from
      1.9 mmol/litre to 23.8 mmol/litre. This magnesium effect was reversed in the
      colon, stomach fundus and uterus of streptozotocin-diabetic animals, with
      contractile sensitivity being enhanced in the presence of increased magnesium
      concentration. In the jejunum, however, the magnesium effect was not reversed by
      STZ-induced diabetes. In diabetic animals, magnesium generally had the opposite
      effect on gastrointestinal and uterine tissues when compared with control
      animals. This suggests that, in the diabetic condition, any altered
      gastrointestinal function may be due to an underlying difference in the
      sensitivity to changes in magnesium.

PMID- 8155486
TI  - Effect of magnesium sulphate infusion on ex vivo platelet aggregation in swine.
AB  - The effect of magnesium sulphate infusion on ex vivo platelet aggregation in 11
      female Yorkshire swine was observed using platelet-rich plasma and different
      agonists (ADP 5 mM; ADP 10 mM and collagen 1 mg/ml). Infusion of 1 g MgSO4 over 1
      h produced a significant decrease in platelet aggregability. A dose-dependent
      effect of different ADP concentrations on platelet aggregation was noticed.
      Platelet inhibition was most consistent when using ADP 5 mM. We estimate this
      concentration of agonist as optimal in swine. The swine model is a good choice
      for investigation of in vivo platelet activation, especially with regard to
      cardiovascular research. We conclude that there is an inhibitory effect of
      supplemental magnesium on ex vivo platelet aggregation in swine with initial
      normomagnesaemia.

PMID- 8155487
TI  - New data about the effects of oral physiological magnesium supplementation on
      several cardiovascular risk factors (lipids and blood pressure).
AB  - In the present study the effect of oral physiological magnesium supplementation
      on atherogenic risk factors such as serum lipids and blood pressure was examined.
      Sixty-nine patients with hyperlipidaemia of Frederickson types IV and IIb were
      investigated with regard to renal function, blood pressure, serum cholesterol,
      triglycerides, HDL-cholesterol and LDL-cholesterol, and plasma and erythrocytic
      magnesium concentrations. All patients were on cholesterol-poor (< 90 mg
      cholesterol/d) and energy-restricted diet (< 1200 kcal/d). Thirty-seven patients
      received 500 mg magnesium (oral) daily as a supplement. All measurements were
      performed before and four weeks after starting treatment. The results of our
      study show that oral physiological magnesium supplementation in addition to the
      usual dietary measures can be beneficial with regard to serum triglycerides
      (values, means +/- SD, decreased from 198.17 +/- 47.01 to 163.20 +/- 40.55 mg/dl,
      P < 0.05), but exerts no positive effect on blood pressure or serum cholesterol.
      Furthermore, erythrocyte magnesium concentration increased significantly during
      oral physiological magnesium supplementation (values, means +/- SD, increased
      from 1.72 +/- 0.22 to 1.91 +/- 0.18 mmol/litre, P < 0.05), whereas plasma
      magnesium concentrations did not change significantly.

PMID- 8155488
TI  - Studies of magnesium in heart transplantation: further insights into magnesium
      and cardiac physiology.
AB  - Magnesium deficit in man is very difficult to detect and even more difficult to
      study. However, a chance observation led to the investigation of cardiac
      transplant recipients as an in vivo model of drug-induced magnesium depletion.
      Clinical circumstances were such that the question of the correlation of serum
      and tissue magnesium levels might be addressed. Using the same model,
      investigation of myocardial calcium levels was undertaken. Significant myocardial
      magnesium depletion accompanied persistent hypomagnesaemia in over 50 per cent of
      cardiac transplant recipients. Repletion of myocardial magnesium occurred some
      weeks later than normalization of serum levels; these time lags may explain the
      lack of correlation of serum and tissue magnesium levels in these circumstances.
      Myocardial calcium levels were generally higher than expected from control
      studies, and were particularly high in magnesium-depleted subjects. These
      findings are keeping with those predicted from animal studies.
      Electrophysiological studies in the transplanted denervated heart are free of
      many of the confounding features of such studies in the native heart. Preliminary
      work involving pacing protocols designed to induce abnormalities of phase 4 of
      the action potential suggests that myocardial magnesium deficit does not produce
      a clinical arrhythmogenic substrate in the denervated heart. However, shortening
      of the effective ventricular refractory period in hypomagnesaemic patients was
      observed, and it was noted that concurrent hypokalaemia in this circumstance
      would be particularly disadvantageous. The data collected in the course of these
      studies is discussed, and mechanisms for the observed benefit of magnesium as a
      possible anti-ischaemic agent in the period following acute myocardial infarction
      are proposed.

PMID- 8155489
TI  - Magnesium and ageing. I. Experimental data: importance of oxidative damage.
AB  - Magnesium status may be compromised with ageing for two reasons: insufficient
      intake (magnesium deficiency) or alterations in magnesium metabolism (magnesium
      depletion). There is a large volume of literature suggesting that magnesium
      deficit contributes to the ageing process and to the vulnerability to age-related
      diseases. One of the biological changes associated with ageing is an increase in
      free radical formation with subsequent damage to cellular processes. Prime
      targets of the more reactive free radicals are unsaturated lipids in cell
      membranes, amino acids in proteins, and nucleotides in DNA. The accumulation of
      unrepaired oxidative damage products may be a major factor in cellular ageing.
      Magnesium-deficient animals show an increased susceptibility to an in vivo
      oxidative stress and their tissues are more susceptible to in vitro peroxidation.
      Moreover, the protective properties of various antioxidant drugs and nutrients
      suggest that free radicals are involved in the injury process of magnesium
      deficiency. The consequences on stress susceptibility, defective membrane
      functions and perturbation of intracellular calcium metabolism, inflammation,
      cardiovascular diseases including atherosclerosis and ischaemia/reoxygenation
      injury, diabetes, fibrosis, immune dysfunction and other diseases associated with
      ageing are presented and discussed.

PMID- 8155491
TI  - Immune reconstitution after chemotherapy for malignant solid tumors in children.

PMID- 8155490
TI  - Magnesium and ageing. II. Clinical data: aetiological mechanisms and
      pathophysiological consequences of magnesium deficit in the elderly.
AB  - Ageing constitutes a risk factor for magnesium deficit. Primary magnesium deficit
      originates from two aetiological mechanisms: deficiency and depletion. Primary
      magnesium deficiency is due to insufficient magnesium intake. Dietary amounts of
      magnesium are marginal in the whole population whatever the age. Nutritional
      deficiencies are more pronounced in institutionalized than in free-living ageing
      groups. Primary magnesium depletion is due to dysregulation of factors
      controlling magnesium status: intestinal magnesium hypoabsorption, reduced
      magnesium bone uptake and mobilization, sometimes urinary leakage,
      hyperadrenoglucocorticism by decreased adaptability to stress, insulin resistance
      and adrenergic hyporeceptivity. Secondary magnesium deficit in ageing largely
      results from various pathologies and treatments common to elderly persons, i.e.,
      non-insulin dependent diabetes mellitus and use of hypermagnesuric diuretics.
      Magnesium deficit may participate in the clinical pattern of ageing, particularly
      in neuromuscular, cardiovascular and renal symptomatologies. The consequences of
      hyperadrenoglucocorticism-the simplest marker of which is non-response to the
      dexamethasone suppression test-may include immunosuppression, muscle atrophy,
      centralization of fat mass, osteoporosis, hyperglycaemia, hyperlipidaemia,
      atherosclerosis, and disturbances of mood and mental performance through
      accelerated hippocampal ageing particularly. It seems very important to point out
      that magnesium deficit and stress aggravate each other in a true 'pathogenic
      vicious circle', particularly in the stressful state of ageing. The importance of
      magnesium deficit in the aetiologies of insulin resistance, and the adrenergic,
      osseous, oncogenic, immune and oxidant disturbances of ageing is still uncertain.
      Oral physiological magnesium supplementation (5 mg Mg/kg/d) is the best
      diagnostic tool for establishing the importance of magnesium deficiency. Too few
      open and double blind studies on the effects of the treatment of magnesium
      deficiency and of magnesium depletion in geriatric populations have been done.
      Further study is necessary to assess the true place of magnesium deficit in the
      pathophysiology of ageing.

PMID- 8155492
TI  - Returning to primary school after treatment for cancer.
AB  - Questionnaires were sent to the teachers of 14 children returning to school after
      treatment for childhood cancer and their 11 siblings. Forty-four control children
      from the same classes were also selected. Behavioral rating scores (Deasy
      Spinetta) showed no differences between cases and siblings or control children in
      terms of learning disabilities, socialization, and emotional behavior. Teachers
      reported few problems on the case children's return to school, although many had
      been anticipated. Most children adapted well, and there were no major changes in
      behavior or performance. Siblings, too, coped well with the experience. The Royal
      Victoria Infirmary at Newcastle, where the children were treated, has two
      community liaison nurses and three social workers. The value of the support that
      they provide to both families and schools is clearly reflected in the ease with
      which children reintegrate into their school environment after what can be, for
      some, a prolonged absence.

PMID- 8155493
TI  - Monosomy 7, diabetes insipidus and acute myeloid leukemia in childhood.
AB  - The triad of diabetes insipidus (DI), monosomy 7, and acute myeloid leukemia in a
      7-year-old boy is described. This triad has been described in adults but not in
      children. The DI ran a transient, self-limiting course and required no specific
      therapy. The pathogenesis of DI remains unknown, and its transient nature may
      result in this component of the triad going unnoticed.

PMID- 8155494
TI  - Resolution of nephrocalcinosis associated with tumor lysis syndrome.

PMID- 8155495
TI  - Transfusion and hepatitis B infection in developing countries.

PMID- 8155496
TI  - History of pediatric hematology and oncology in Greece.
AB  - The history of pediatric hematology and oncology in ancient and modern Greece is
      reviewed. Ancient Greek literature concerning cancer starts with Hippocrates, is
      enriched by Galen during the 2nd century AD, and ends with the end of the
      Byzantine period. Hematology and oncology in modern Greece were adopted as fields
      of special interest by a few Greek pediatricians. Their work constituted the
      basis for and the start of pediatric hematology and oncology, which has followed
      the advances of science ever since.

PMID- 8155497
TI  - Pediatric hematology and oncology in Pakistan.
AB  - Pediatric hematology and oncology has only recently started developing within
      Pakistan, with centers in Islamabad, Lahore, Karachi, and Multan. Efforts are
      being made to update blood bank facilities and to standardize the level of care
      being provided throughout the country. A pediatric oncology group has recently
      been established. A lot of work still needs to be done, however.

PMID- 8155498
TI  - Recovery of blood lymphocytes and serum immunoglobulins after treatment of solid
      tumors in children.
AB  - Hematologic and immunologic recovery after treatment for different solid tumors
      was investigated in 11 children at cessation of therapy and at 1, 3, 6, 9, and 12
      months after cessation of therapy by determining blood total leukocyte counts,
      leukocyte differentials, lymphocyte subsets, concentrations of serum
      immunoglobulins (Igs), and serum IgG subclasses. Lymphocyte subsets were analyzed
      from mononuclear cell fractions by flow cytometry and use of monoclonal
      antibodies CD3, CD20, CD4, CD8, CD4/Leu-8, and CD4/CD45RA. Peripheral blood total
      leukocyte, neutrophil, and B-cell counts recovered early, although defective B
      cell function was seen in several patients. T-cell counts and thus total
      lymphocyte counts required a longer time to normalize even though inducer T-cell
      subsets (CD4+CD45RA+ and CD4+Leu-8-) were present in normal or high amounts. CD8+
      T cells recovered earlier than CD4+ T cells. The lymphocyte, B-cell and T-cell
      counts of most patients normalized during the first 12 months after therapy.
      Recovery of total lymphocyte and T-cell counts was slow in patients with
      Hodgkin's disease or Burkitt's lymphoma and rapid in nephroblastoma. Radiotherapy
      seemed to prolong the recovery of study parameters, particularly T-cell recovery.

PMID- 8155499
TI  - Dosimetry of radiation scattered to thyroid gland from prophylactic cranial
      irradiation for childhood leukemia.
AB  - Dosimetry of radiation scattered to the thyroid gland was performed in 17
      children (9 boys, 8 girls) who were treated for acute lymphoblastic leukemia and
      received cranial irradiation for prophylaxis against central nervous system
      leukemia at a median age of 4 years and 2 months (range, 1 year and 1 month to 14
      years). The absorbed dose to the thyroid gland in these children ranged from 0.7%
      to 7.3% of the dose delivered to the cranium. Thus the total dose to the thyroid
      gland ranged from 0.13 to 1.32 Gy by the end of the entire course of cranial
      irradiation. Doses tended to be larger in younger children, but the radiation
      source also had a large influence on the dose to the thyroid gland; that is, the
      absorbed dose to the thyroid gland with delivery by linear accelerator was
      smaller than that by cobalt irradiation. Long-term survivors treated with cranial
      irradiation for acute leukemia during childhood should be followed for the
      possible development of thyroid diseases, including malignant tumors, for a long
      period.

PMID- 8155500
TI  - Dosimetry and radiation scattered to the thyroid gland from prophylactic cranial
      irradiation for childhood leukemia.

PMID- 8155501
TI  - Value of DNA analysis with multiple DNA probes for the detection of hemophilia A
      carriers.
AB  - Detection of hemophilia carriers is an important issue and should be addressed
      with great care. The allelic frequencies of three intragenic probes (Bcl I for
      probe p114.12, Xba I for probe p482.6, and Bgl I for probe C) and one linked
      probe (Bgl II for probe DX 13) are reported, together with their diagnostic yield
      singly and in combination. In this series, 725 individuals (405 females) in 156
      families were analyzed for restriction fragment-length polymorphisms. A total of
      255 females (63%) were found to be informative for their carrier state with one
      or more probes. The most informative intragenic probe was p482.6 (useful in 49%
      of informative females). The most informative probe was DX 13 (useful in 59% of
      informative females), but this is a linked probe that carries a 5% risk of cross
      over. By the use of probes p114.12, p482.6, and DX 13, almost 98% of all the
      informative females could be detected. In about 71% of families with a family
      history and a known carrier, prenatal diagnosis was feasible.

PMID- 8155502
TI  - Antiinfective prophylaxis with ceftazidime and teicoplanin in children undergoing
      high-dose chemotherapy and bone marrow transplantation.
AB  - Sixty children treated for solid tumors with high-dose chemotherapy followed by
      bone marrow transplantation were randomly assigned to one of two antibiotic
      protocols. Group A received prophylaxis consisting of ceftazidime plus
      teicoplanin beginning before the onset of aplasia and fever; group B received
      exactly the same antibiotic regimen but beginning at the onset of fever. The two
      groups were compared in terms of the rate of septicemia, fever of unknown origin,
      the time-lapse before the appearance of septicemia, the sensitivity of the
      causative organisms to the antibiotics, the effect of the latter on the
      intestinal flora, and the rate of fungal infections. The incidence of septicemia
      was significantly lower in group A (6.6%) than in group B (24.0%), mainly due to
      the prevention of episodes of early onset. Similarly, the appearance of the first
      episode of fever was delayed in group A, and the overall duration was reduced.
      Amphotericin B was prescribed empirically with the same rule in both groups, but
      three children in group A did not require amphotericin B. The effect on the
      intestinal flora was similar in the two groups; it must, however, be closely
      monitored so that the presence of potential pathogens can be dealt with
      appropriately.

PMID- 8155503
TI  - Light chain ratios and concentrations of immunoglobulins G, A, and M in childhood
      common acute lymphoblastic leukemia.
AB  - The light chain ratios and the concentrations of immunoglobulin G (IgG), IgA, and
      IgM were measured before, during, and after antileukemic therapy in 10 patients
      with common acute lymphoblastic leukemia. The concentrations of IgG, IgA, and IgM
      decreased substantially during treatment but recovered slowly after cessation of
      the therapy. The light chain ratios were not systematically affected, but at
      diagnosis the kappa/lambda ratios of total serum Igs, IgG, and in particular IgM
      were somewhat lower in the patient group compared with an age-matched reference
      group. It is concluded that, despite a decrease in serum Ig concentrations,
      virtually normal kappa/lambda ratios are preserved, indicating that kappa and
      lambda syntheses are affected to the same extent. These ratios remained normal
      for age during the recovery of the serum Ig concentrations; the features as
      described for the development of the light chain ratios in childhood were not
      observed.

PMID- 8155504
TI  - Impact of gender on the natural history of neuroblastoma.
AB  - To study of the possible impact of gender on the natural history of
      neuroblastoma, the medical records of 136 consecutive children with that
      diagnosis treated at the Children's Hospital of Pittsburgh from 1975 to 1992 were
      reviewed. An attempt was made to investigate the association between sex and age
      at diagnosis, primary tumor site, stage, and histology. Although overall
      male:female ratio was only 1.3:1, in the group of 17 patients who were older than
      six years at diagnosis the incidence was 2.0:1. Primary tumor site also could be
      stratified on the basis of sex, with twofold more adrenal tumors occurring in
      boys than in girls (P = 0.012). Based on retrospective data, there was no clear
      association between sex and stage or extent of histologic differentiation.
      Because these observations cannot readily be explained on the basis of male
      predominance in the population at large or on uneven referral patterns, they
      deserve further examination in larger series, such as those of cooperative
      groups.

PMID- 8155505
TI  - Does rapidly progressive iron overload in a young girl with sideroblastic anemia
      also signify the presence of hereditary hemochromatosis?
AB  - A severely anemic 3-year-old girl with refractory sideroblastic anemia and
      fulminant, fatal hemochromatosis is described. The patient had transfusion
      dependent anemia with clinical cardiac, liver, and endocrine dysfunction that
      resulted from iron loading. The patient was minimally transfused, and
      deferoxamine chelation was started at age 34 months. Despite treatment, the
      patient died at age 46 months as a result of severe iron overload. Sideroblastic
      anemia and iron overload in childhood are reviewed, and a pathophysiologic
      mechanism for the patient's clinical course is postulated.

PMID- 8155506
TI  - Instrumentation in dermatologic surgery.
AB  - The practice of dermatology has changed greatly over the past 2 decades. This
      change has been partly characterized by an increased emphasis on the surgical
      approach to the diagnosis and treatment of skin disease. This new emphasis within
      the practice of dermatology necessarily alters the basic equipment and
      instrumentation needed to begin and maintain a dermatology practice in the 1990s.
      The following article is intended to provide the interested reader with a sound
      and rational basis for selection of surgical instruments to incorporate into his
      or her particular level of surgical practice.

PMID- 8155507
TI  - The dermatologic surgical suite.
AB  - In summary the size, layout, surgical lighting, and operative table are the most
      important variables in providing a comfortable, efficient surgical suite. Each
      physician will develop their own likes and dislikes when using and experimenting
      with various instruments and surgical devices. Wherever possible, trial periods
      should be obtained before committing excessive funds to major purchases. Nothing
      replaces personal experience in making such selections. A well-equipped, well
      designed surgical suite improves the experience for both patients and the
      dermatologic surgeon.

PMID- 8155508
TI  - Basic suture materials and suturing techniques.
AB  - There is a need for surgeons to be able to make a logical decision regarding
      which suture materials to use in a given clinical situation because the choice of
      wound-closure materials may make a difference in wound healing and the ultimate
      functional and cosmetic result obtained. This article will review the basic
      physical, handling, and tissue-reaction characteristics of commonly used suture
      materials. Basic suturing techniques are also reviewed. Knowledge of multiple
      suturing techniques provides versatility, individuality, and optimal closure of
      surgical wounds.

PMID- 8155509
TI  - Antibiotic prophylaxis.
AB  - The appropriate use of antibiotic prophylaxis is confusing for all surgeons and
      it is certainly not straight-forward for dermatologists. There are no set
      guidelines which encompass skin surgery. This article reviews antibiotic
      prophylaxis both to prevent wound infections and to prevent endocarditis. Some of
      the issues and controversies surrounding the use of antibiotic prophylaxis are
      discussed, and guidelines are provided which should be of assistance to those who
      perform dermatologic surgery.

PMID- 8155510
TI  - Local anesthesia for dermatologic surgery.
AB  - Knowledge of local anesthesia is critically important to perform dermatologic
      surgery. The objective of this article is to provide an updated review of local
      anesthesia. The principles of local anesthesia as it pertains to dermatologic
      surgery are reviewed. New methods of delivering local anesthesia are also
      presented. Local anesthetics are safe, effective drugs that provide transient
      insensibility to pain in a limited area of skin. There are a variety of methods
      of inducing local anesthesia which can be tailored to the requirements of the
      contemplated procedure. Local anesthetics allow dermatologists to perform a range
      of procedures safely. Recent developments in topical anesthetics and in tumescent
      local anesthesia have provided the dermatologic surgeon other methods of
      delivering local anesthesia.

PMID- 8155512
TI  - Introduction to lasers.
AB  - This article is an overview of the lasers that are presently available for
      dermatologic use. Each type of laser is discussed, including how it works, its
      indications, possible complications, physics, and safety issues.

PMID- 8155511
TI  - The superficial neurovasculature of the head and neck.
AB  - The majority of dermatologic procedures are performed in the sun-damaged regions
      of the head and neck. These regions have special cosmetic and functional
      importance, and dermatologists should become familiar with the underlying
      structures. Even though all the major nerves and vessels arborize below the
      superficial fascia, cutaneous atrophy and fibrosis from previous surgeries can
      make these neurovascular structures susceptible to damage from superficial
      procedures. Hence, it is advisable to utilize blunt dissection whenever possible,
      and to identify vital structures when working in their vicinity.

PMID- 8155513
TI  - Introduction to cosmetic surgery.
AB  - Patients seeking information on improving their appearance is becoming
      increasingly popular, and dermatologists are often the first to be consulted. It
      is therefore important for the dermatologist to acknowledge the patient's
      concerns and if they are not willing or capable of addressing these needs, one
      should refer them to an appropriate health care provider. However, if the
      dermatologist does elect to provide a service, it is crucial not only to obtain
      the knowledge and technical skill but the mechanism to select and recognize who
      is an acceptable candidate from both anatomic and psychological perspectives.

PMID- 8155515
TI  - Chagas disease. Elimination of transmission.

PMID- 8155514
TI  - Global programme on AIDS.

PMID- 8155516
TI  - Rabies. Oral immunization of foxes.

PMID- 8155517
TI  - Expanded programme on immunization (EPI). Poliomyelitis eradication.

PMID- 8155518
TI  - Poliomyelitis eradication.

PMID- 8155519
TI  - Surveillance of cholera due to Vibrio cholerae O139.

PMID- 8155520
TI  - The health and wealth of the nation. Interview by Simon Canning.

PMID- 8155521
TI  - Midwifery: hailing a new philosophy.

PMID- 8155522
TI  - Residential care: money troubles.

PMID- 8155523
TI  - Asthma and the menstrual cycle (continuing education credit).

PMID- 8155524
TI  - A guide to calcium channel blockers.

PMID- 8155525
TI  - Health promotion: time for an audit.
AB  - This article examines how health promotion models are used in practice. The
      conceptual base of health promotion models is reviewed with particular relevance
      to the interaction between professional and client, and in relation to The Health
      of the Nation targets. The author argues that health promotion models are being
      used by professionals purely to achieve targets and, as a consequence, important
      information on clients' socio-economic circumstances is being ignored. A
      framework for a 'health promotion audit' is offered.

PMID- 8155526
TI  - Theatre nursing: the fight for survival.
AB  - The sense of threat operating department nurses have been feeling recently has
      been exacerbated by many of the newer nursing education programmes not defining
      clinical placements in theatre as a necessity for students. This, the author
      argues, will have far-reaching consequences which include a decline in the number
      of qualified nurses in the operating department, higher qualified nurse turnover
      and a decline in patient-care standards. Operating department nurses must be
      prepared to prove their worth in the increasingly competitive and cost-conscious
      clinical world.

PMID- 8155527
TI  - Violence: a thumping bad idea.

PMID- 8155528
TI  - Computer reviews. That's Stat!

PMID- 8155529
TI  - Tissue Viability Society. Preventing pressure sores in wheelchair users.

PMID- 8155530
TI  - Tissue Viability Society. Choosing a mattress: research findings.

PMID- 8155531
TI  - The number of HIV positive people in Scotland.

PMID- 8155532
TI  - New test may predict progression of HIV.

PMID- 8155533
TI  - Increased replication in HIV/HSV co-infection.

PMID- 8155535
TI  - Reward systems: panning pay.

PMID- 8155534
TI  - Pay award: firing the first shots.

PMID- 8155536
TI  - HIV/AIDS. Anonymous testing: legal or illegal?

PMID- 8155537
TI  - Community nurses & discharge planning.
AB  - The role of community nurses in discharge planning for elderly patients leaving
      hospital is of increasing importance in the wake of the NHS and Community Care
      Act 1990. Community nurses can play a key role in contributing to pre-discharge
      assessments and in providing continuing post-discharge assessment and care. The
      Nursing Research Unit at the University of Edinburgh conducted a survey early in
      1993, just prior to implementation of the Community Care Act in Scotland, to
      ascertain the views and experiences of a national 1 in 3 sample of community
      nurses relating to the discharge of elderly people from acute hospitals. This
      article presents the results of that survey and offers recommendations regarding
      the role of community nurses in discharge planning for elderly patients.

PMID- 8155538
TI  - Managing brachial plexus injuries.
AB  - People who are injured in severe traumatic incidents such as motorcycle accidents
      and knife or gunshot attacks generally require intensive, life-saving surgical
      intervention for head, chest or spinal injuries. One of the problems associated
      with such accidents is brachial plexus injury. Although this does not pose a
      threat to life, it can result in chronic hand and arm disability and pain. The
      author describes the surgical and nursing management of these devastating
      injuries.

PMID- 8155539
TI  - The named nurse and the named teacher.

PMID- 8155540
TI  - Mental health nurses' views of doctors.
AB  - Love them or loathe them, doctors continue to exert a strong influence on the
      nursing profession. Some research into the relationships between general nurses
      and doctors has been carried out, but much less has been undertaken in the field
      of mental health. The author completed a survey of nursing staff in one
      psychiatric hospital, specifically aiming to discover their awareness of junior
      doctors' on-call activities and re-imbursements, and their views on doctors'
      attitudes in general. The results suggest a perhaps more positive perspective
      than may have been guessed, but continued ignorance of the characteristics of
      being 'on-call' was evident.

PMID- 8155541
TI  - Love isn't.

PMID- 8155542
TI  - One minute wisdom. Tory attacks on mothers.

PMID- 8155543
TI  - The emperor's new clones.

PMID- 8155544
TI  - Don't play the blame game.

PMID- 8155545
TI  - Temper temper.

PMID- 8155546
TI  - Immunisation: flu jab.

PMID- 8155547
TI  - Women's network. Women's lip.

PMID- 8155548
TI  - Macmillan nurses: fighting cancer with more than medicine (continuing education
      credit).

PMID- 8155549
TI  - Euroquan. Relieving the pressure.

PMID- 8155550
TI  - Euroquan. Striving for excellence.

PMID- 8155551
TI  - Euroquan. Clarity begins at Stockholm.

PMID- 8155552
TI  - Euroquan. Protocol matters.

PMID- 8155553
TI  - Euroquan. Quality questions.

PMID- 8155554
TI  - Euroquan. Vive la qualite des soins (long live nursing quality).

PMID- 8155555
TI  - Euroquan. Taking the bull by the horns.

PMID- 8155556
TI  - Developing countries: the culture of caring.

PMID- 8155558
TI  - Trauma care: flying to the rescue.

PMID- 8155557
TI  - Mental health: working in partnership.

PMID- 8155559
TI  - Continuing education: fishing in murky waters.

PMID- 8155560
TI  - Clinical involvement of midwife teachers.
AB  - Changes in management and educational structures have severely curtailed
      opportunities for midwifery teachers to engage in clinical practice outside their
      commitment to teaching students in clinical areas. The author outlines the past
      and current positions in this regard, and explains how a team of teachers from
      her department devised a system which ensures that 20 per cent of their time (or
      45 days a year) can be spent in clinical practice.

PMID- 8155561
TI  - Promoting health with elderly people.
AB  - Outpatient departments provide a valuable opportunity to give elderly people
      education and information about health promotion. A study of 23 elderly patients
      showed that they spent long periods waiting in outpatient departments, time which
      they felt could be used profitably for health promotion. The older patients in
      the sample had less knowledge about their health than the younger patients,
      requesting information on functional aspects of health and services available to
      them in the community. It is recommended that health promotion should be
      incorporated into planned care in outpatient clinics, and that staff need to
      undergo further training to fulfil this role.

PMID- 8155562
TI  - Lifting: why nurses follow bad practice.
AB  - This article reports on a research study of a group of third-year undergraduate
      student nurses, investigating their use of lifting techniques and their potential
      to conform to ward practice in the selection of lifts. A questionnaire which
      included a vignette was administered to 19 students. Results showed that 50 per
      cent would conform to the selection of a two-person lift by a staff nurse even
      when they knew that the lift was unsafe. The authors suggest possible variables
      which may influence the selection of lifts.

PMID- 8155563
TI  - Mental health: crazed, bigoted and paranoid.

PMID- 8155565
TI  - Sister Susie. Susie's psychotic TV episode.

PMID- 8155564
TI  - Community care: out with the old.

PMID- 8155566
TI  - No sex for UK nurses.

PMID- 8155567
TI  - Damn lies.

PMID- 8155569
TI  - Professional boundaries: growing gains.

PMID- 8155568
TI  - Socio what?

PMID- 8155570
TI  - Community care: dinner a la cart.

PMID- 8155571
TI  - Making decisions (continuing education credit).

PMID- 8155572
TI  - Formation of morphological differentiation patterns in the ascomycete Neurospora
      crassa.
AB  - Morphological differentiation patterns--among them concentric rings and radial
      zonations--can be induced in the band-mutant of Neurospora crassa by appropriate
      experimental conditions, in particular by a mere shift of certain salt
      concentrations in the medium. The role of initial experimental conditions is
      examined and, furthermore, the influences of artificially induced phase
      differences are analyzed with respect to pattern formation. While the concentric
      ring pattern is due to some (endogenous) circadian rhythmicity within every
      hypha, nothing is known about the underlying mechanism of radial zonation
      development. Various hypotheses were tested with the help of a cellular automaton
      model which mimics growth, branching and differentiation of a fungal mycelium. In
      particular, sufficient conditions are provided which imply the formation of
      radial spore zonations. These conditions postulate a rather homogeneous
      microscopic hyphal branching pattern and induction of spore differentiation by
      means of an activator-inhibitor system. Furthermore, a working hypothesis for the
      formation of spore patterns in Neurospora crassa is suggested which is based on
      an extracellular control of fungal differentiation.

PMID- 8155573
TI  - PDGF-BB and TGF-alpha rescue gastrulation, spiculogenesis, and LpS1 expression in
      collagen-disrupted embryos of the sea urchin genus Lytechinus.
AB  - Development and LpS1 transcription in Lytechinus embryos are arrested at the
      mesenchyme blastula stage when collagen deposition is inhibited by the lathrytic
      agent beta-aminopropionitrile (BAPN) or by proline analogs. We found that human
      recombinant platelet derived growth factor-BB (PDGF-BB) and transforming growth
      factor-alpha (TGF-alpha) synergistically rescue collagen
      disrupted/developmentally arrested L. pictus and L. variegatus embryos so that
      development and RNA accumulation of LpS1 proceed. In addition, nonspecific
      antagonists of PDGF block gastrulation and LpS1 RNA accumulation. The embryos
      recover and LpS1 RNA accumulation resumes when the antagonists are removed. These
      data suggest that a growth factor mediated pathway, associated with the ECM, is
      required for sea urchin gastrulation, spiculogenesis, and LpS1 gene activation.

PMID- 8155574
TI  - Embryonic stem cells differentiate in vitro into cardiomyocytes representing
      sinusnodal, atrial and ventricular cell types.
AB  - Pluripotent embryonic stem cells (ESC, ES cells) of line D3 were differentiated
      in vitro and via embryo-like aggregates (embryoid bodies) of defined cell number
      into spontaneously beating cardiomyocytes. By using RT-PCR technique, alpha- and
      beta-cardiac myosin heavy chain (MHC) genes were found to be expressed in
      embryoid bodies of early to terminal differentiation stages. The exclusive
      expression of the beta-cardiac MHC gene detected in very early differentiated
      embryoid bodies proved to be dependent on the number of ES cells developing in
      the embryoid body. Cardiomyocytes enzymatically isolated from embryoid body
      outgrowths at different stages of development were further characterized by
      immunocytological and electrophysiological techniques. All cardiomyocytes
      appeared to be positive in immunofluorescence assays with monoclonal antibodies
      against cardiac-specific alpha-cardiac MHC, as well as muscle-specific sarcomeric
      myosin heavy chain and desmin. The patch-clamp technique allowed a more detailed
      characterization of the in vitro differentiated cardiomyocytes which were found
      to represent phenotypes corresponding to sinusnode, atrium or ventricle of the
      heart. The cardiac cells of early differentiated stage expressed pacemaker-like
      action potentials similar to those described for embryonic cardiomyocytes. The
      action potentials of terminally differentiated cells revealed shapes,
      pharmacological characteristics and hormonal regulation inherent to adult
      sinusnodal, atrial or ventricular cells. In cardiomyocytes of intermediate
      differentiation state, action potentials of very long duration (0.3-1 s) were
      found, which may represent developmentally controlled transitions between
      different types of action potentials. Therefore, the presented ES cell
      differentiation system permits the investigation of commitment and
      differentiation of embryonic cells into the cardiomyogenic lineage in vitro.

PMID- 8155575
TI  - Molecular organisation and expression pattern of the segment polarity gene fused
      of Drosophila melanogaster.
AB  - The Drosophila segment-polarity gene fused (fu) is required for pattern formation
      within embryonic segments and imaginal discs. We previously reported that the 5'
      part of the fused gene is homologous to the catalytic domain of serine/threonine
      kinases. We present here the sequence of the complete transcription unit, which
      predicts a 805 amino acid long protein. The kinase domain actually corresponds to
      268 amino acids in the N-terminal part, and no known function can be attributed
      to the rest of the putative FUSED protein. Transcripts from the fused gene have
      been characterized: a unique 3.2 kb fused transcript is produced in nurse cells,
      in low abundance, from stage 8 of oogenesis, and persistently through the rest of
      oogenesis. In embryos, this transcript is evenly distributed in all embryonic
      cells until the extended germ band stage, after which its amount strongly
      decreases. Ubiquitous expression is detected later in imaginal wing and leg
      discs. Possible roles of the FUSED protein in signal transduction pathways
      required for intercellular communication at different stages of development are
      discussed.

PMID- 8155577
TI  - In vivo functional characterization of an ecdysone response enhancer in the
      proximal upstream region of the Fbp1 gene of D. melanogaster.
AB  - Transcription of the D. melanogaster Fat-body-protein-1 (Fbp1) gene is induced by
      the steroid hormone 20-hydroxyecdysone and is restricted to the fat body tissue
      at the end of the third larval instar. The location and functional properties of
      the Fbp1 cis-acting regulatory sequences contained in the region from -1386 to
      +80 relative to the transcription start were examined by transformation using
      hybrid constructs with the Adh or lacZ genes as reporters. Regulatory element(s)
      required for the full level of transcription of the Fbp1 gene were located
      between positions -1386 and -138. Sequences between -138 and -68 were able to
      drive transcription from a heterologous minimal promoter in the fat body of late
      third instar larvae. Remarkably, these sequences also conferred 20
      hydroxyecdysone inducibility and behaved as an enhancer-like element. These
      results provide the first functional characterization, at the level of the whole
      organism, using a direct in vivo ecdysone induction assay, of a discrete ecdysone
      response element.

PMID- 8155576
TI  - Xl-fli, the Xenopus homologue of the fli-1 gene, is expressed during
      embryogenesis in a restricted pattern evocative of neural crest cell
      distribution.
AB  - The Xenopus laevis fli cDNA, belonging to the ets family of transcription
      factors, was isolated from a library prepared from unfertilized eggs. It encodes
      a polypeptide with extensive homology to murine and human Fli proteins. The long
      3'-untranslated region contains five nuclear polyadenylation signals and three
      cytoplasmic polyadenylation elements, as well as many A/T rich elements. Two
      polyadenylated transcripts appear at the early neurula and accumulate up to the
      tadpole stage. In situ hybridization reveals an expression in territories invaded
      by neural crest cells. In the head region, fli is expressed in the peri-ocular
      zone, in the branchial buds and at the level of the brain floor. In the trunk, a
      metamerized expression is detected in the dorsum. At a lower level, the tailbud
      and the peri-cardiac region also appear positive.

PMID- 8155578
TI  - V(+)-fibronectin expression and localization prior to gastrulation in Xenopus
      laevis embryos.
AB  - The V-region represents one of three alternatively spliced segments in Xenopus
      fibronectin. Here, we identify this V-region as binding epitope of the monoclonal
      antibody (MAb 6D9) that we generated against Xenopus plasma fibronectin. By the
      use of this antibody we obtained new results that change the present view of the
      fibronectin expression pattern before gastrulation: (1) the V(+)-fibronectin is
      the major isoform expressed during early development since only a single
      fibronectin band is found in Western blots up to tadpole stages. (2) In contrast
      to previously published data we demonstrate that fibronectin expression is
      induced by progesterone during oocyte maturation. (3) During cleavage stages the
      protein is stored in the cytoplasm where it is predominantly associated with
      plasma membranes. Immunoelectronmicroscopy reveals that V(+)-fibronectin is
      present at the surface of animal pole blastomeres and secreted into intercellular
      spaces. This extracellular localization of fibronectin is predominantly observed
      in the marginal zone, surrounding single cells of the outer cell layer baso
      laterally. In the vegetal hemisphere V(+)-fibronectin is restricted to the
      cytoplasm and accumulated at plasma membranes. With the onset of gastrulation the
      intracellular and membrane associated fibronectin disappears and fibronectin
      becomes detectable at the blastocoel roof. Since reaggregation of dissociated
      blastula cells was not blocked by addition of GRGDS peptide or antibodies against
      fibronectin, we assume that the early expression and secretion of fibronectin
      serves as store to allow a rapid matrix assembly with onset of mesodermal cell
      migration.

PMID- 8155579
TI  - Retinoic acid affects central nervous system development of Xenopus by changing
      cell fate.
AB  - Retinoic acid (RA) may play a role in anterior-posterior (A-P) patterning in the
      central nervous system (CNS) of vertebrates. To understand this role, Xenopus
      embryos were treated with increasing doses of all-trans RA at the late gastrula
      to early neurula stage, and changes in the brain were assessed. When embryos were
      treated with a low dose of 10(-8) M RA, alterations of the brain were observed: a
      120% increase in the expression of a neural-specific marker, XlPOU 1, in the
      brain and eye with a concurrent loss of the forebrain. Higher doses of RA led to
      progressively more severe truncations in the brain and a loss of XLPOU 1
      expression. Most importantly, after observing changes in the RA-treated embryos,
      we determined that the lineage of cells that contribute to the brain of these
      embryos do not die but change their fate. With higher doses of RA (> or = 10(-7)
      M), the normal cell fate of the A1 lineage was changed from a mostly neuronal
      phenotype to an epidermal one. Our data suggest that exogenous RA or a closely
      related derivative causes changes in cell fate of the A1 lineage which may in
      part be responsible for alterations in the developing CNS.

PMID- 8155580
TI  - CRUMBS is involved in the control of apical protein targeting during Drosophila
      epithelial development.
AB  - The gene crumbs (crb) of Drosophila encodes a transmembrane protein with 30 EGF
      like and four laminin A G-domain-like repeats in its extracellular domain. Loss
      of-function mutations lead to severe disorganization and degeneration of
      ectodermally derived embryonic epithelia. In embryos homozygous for crb8F105, an
      amorphic allele, the CRUMBS protein is diffusely distributed in the cytoplasm
      instead of being apically localized as in wild-type; this mislocation occurs
      before any morphologically detectable cellular phenotype becomes manifest,
      suggesting that apical targeting of proteins is affected in crb mutant embryos.
      This has been confirmed by using an antibody directed against YELLOW, another
      apically expressed protein. A single base exchange in crb8F105 leads to the
      introduction of a premature stop codon, thus eliminating the C-terminal part of
      the cytoplasmic domain. A possible role for crb in controlling apical-basal
      polarity is discussed.

PMID- 8155581
TI  - Altered Pax gene expression in murine notochord mutants: the notochord is
      required to initiate and maintain ventral identity in the somite.
AB  - We have characterised the patterning capacity of the notochord on the somite
      using the murine Pax-1 gene as a ventral, and Pax-3 as a dorsal molecular marker.
      As model systems we chose the four mouse notochord mutants Brachyury curtailed
      (Tc), Danforth's short tail (Sd), Pintail (Pt) and truncate (tc). Their notochord
      either is initially absent or progressively degenerates. The use of these mutants
      enabled us to compare the effect of graded notochord deficiencies. All four
      mutants show premature termination of the vertebral column. This phenotype can be
      traced back to an impaired dorsoventral specification of the somites. In tc/tc
      and Tc/+ embryos the notochord in the affected regions is missing from the
      beginning. Consequently, Pax-1 is never activated, and Pax-3 remains to be
      expressed in the entire somite. In contrast, in Sd and Pt embryos the notochord
      secondarily degenerates. At the end of the prevertebral column Pax-1 expression
      is lost, while the Pax-3 signal occupies the former Pax-1 expressing zone. The
      altered pax gene expression in the notochord mutants suggests that the notochord
      is required for two processes in the dorsoventral patterning of the somite: first
      the induction of ventral structures, and second the maintenance of the ventral
      fate.

PMID- 8155582
TI  - Expanded, a negative regulator of cell proliferation in Drosophila, shows
      homology to the NF2 tumor suppressor.

PMID- 8155583
TI  - ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic
      cell junctions.

PMID- 8155584
TI  - Sequential expression of HNF-3 beta and HNF-3 alpha by embryonic organizing
      centers: the dorsal lip/node, notochord and floor plate.
AB  - Axial patterning in the nervous system of vertebrate embryos depends on inductive
      signals that derive from the organizer region (the dorsal lip in amphibians and
      the node in birds and mammals) and leter from the notochord and floor plate.
      Previous studies have shown that Pintallavis, a member of the HNF-3/fork head
      transcription factor family, is expressed selectively by these cell groups in
      frog embryos and may be involved in regulating neural development. We report here
      that in early rat and mouse embryos, the embryonic endoderm, the node, the
      notochord and the floor plate express two related transcription factors, HNF-3
      alpha and HNF-3 beta, which also function in the control of liver cell
      differentiation. Early embryonic tissues express variant forms of HNF-3 beta
      which derive from the use of 5' alternative exons. Within the organizer region
      and notochord, HNF-3 beta and HNF-3 alpha have distinct temporal patterns of
      expression and appear in partially overlapping domains. The early expression
      pattern of mammalian HNF-3 beta in the node, notochord and midline neural plate
      cells is similar to that of Pintallavis in frog embryos. There does not appear to
      be a Pintallavis homologue in mice. This prompted us to isolate and analyze the
      expression of the frog HNF-3 beta gene. In frog embryos, HNF-3 beta is expressed
      in the dorsal lip, pharyngeal endoderm and floor plate. In contrast to mammalian
      HNF-3 beta, the onset of frog HNF-3 beta expression in neural tissue occurs after
      neural tube closure. Thus, the combined expression patterns of Pintallavis and
      HNF-3 beta in frogs is equivalent to that of HNF-3 beta in rats and mice. Within
      neural tissue, the onset of expression of these regulatory genes define
      successive stages in the differentiation of floor plate cells. The results
      reported here show that closely related members of the HNF-3/fork head gene
      family are expressed by axial midline cell groups involved in neural induction
      and patterning and suggest the involvement of these genes in the development of
      the vertebrate neuraxis.

PMID- 8155585
TI  - Selective radionuclide localisation in primary liver tumours (pilot study).
AB  - The therapeutic potential of 131I-Lipiodol was investigated in 8 patients with
      cholangiocarcinoma (CCA) and 15 patients with hepatocellular carcinoma (HCC).
      Patients received one or two doses of 131I-Lipiodol via hepatic arterial
      injection. The mean total administered activity was 668 (SD 325) MBq in CCA and
      953 (SD 477) MBq in HCC. One patient with CCA retained 131I-Lipiodol. The
      cumulative radiation dose was 9.6 Gy to tumour, 6.4 Gy to liver and 1.5 Gy to
      lung. The patient remained asymptomatic with no evidence of tumour 30 months from
      the start of treatment, whereas the remaining 7 patients exhibited tumour
      progression. The mean survival in CCA was 11.6 (SD 14.5) months. All 15 patients
      with HCC retained 131I with tumour: liver ratios of up to 30:1. The mean
      cumulative radiation dose was 34.7 (SD 32.4) Gy to tumour, 3.3 (SD 1.5) Gy to
      liver and 4.4 (SD 2.3) Gy to lung. The mean dose per administered activity was
      3.8 (SD 4.1) cGy/MBq. Partial response (reduction in tumour size > 50%) was
      observed in 6 patients (40%). The mean survival was 7.1 (SD 6.0) months. 131I
      Lipiodol can deliver highly selective internal irradiation to foci of HCC with
      evidence of objective response and may be the treatment of choice for patients
      with cirrhosis and a small tumour.

PMID- 8155586
TI  - Management of isolated gastric varices by devascularization and proximal
      gastrectomy in cirrhotic patients.
AB  - Twenty patients with liver cirrhosis were treated by surgery for bleeding from
      isolated gastric varices. The presence of tortuous and engorged gastric veins
      connecting with a large splenorenal shunt was demonstrated by transhepatic
      portography in all patients. The surgical procedures consisted of splenectomy,
      proximal gastrectomy, paragastric devascularization, and ligation of the
      splenorenal shunt. Sixteen patients survived the surgery. Four deaths were caused
      by emergency operation for uncontrollable hemorrhage in extremely poor risk
      patients. Of the 16 survivors, 15 had been followed with endoscopy and
      portography for a mean period of 42 months. The other one died of hepatocellular
      carcinoma three years after surgery. There was no bleeding episode during the
      period of follow-up in these patients. Recurrent esophageal varices of mild
      degree were documented by endoscopy and portography in three patients.
      Portography demonstrated that several newly formed retroperitoneal veins arising
      from the junction of the portal and superior mesenteric veins joined to form
      recurrent varices in these three patients. There was no significant change of the
      mean portal venous pressure before and after surgery. Our data reveals that
      elective surgery may provide satisfactory results in patients with isolated
      gastric varices. Transhepatic portography is the method of choice in radiologic
      investigation for prominent gastric varices.

PMID- 8155587
TI  - Does liver transplantation in the rat cause a regenerative response. The effect
      of arterialisation of the graft.
AB  - This study was conducted to determine the pattern of early regenerative response
      to orthotopic intact liver transplantation in the rat and to investigate whether
      the response differed in grafts with or without revascularisation of the arterial
      bed. Outbred male Long Evans (LE-LE allogeneic, non rejector) rats weighing 300
      350g were subjected to orthotopic intact liver allograft using a "sleeve"
      anastomosis for the hepatic artery. Total warm ischaemia ranged from 19 to 34
      minutes and no storage was employed. Comparison was made with a group of control
      rats which were subjected to 25 minutes total inflow occlusion and regeneration
      was measured with tissue thymidine kinase (TK) and mitotic figures. Samples were
      taken at 1, 2, 4, 7, 10 and 20 days post-operatively. Plasma aspartate
      aminotransferase (AAT) and light microscopy were used to evaluate hepatocyte
      necrosis. There was a brief sharp increase in TK and AAT in the first 24 hours
      after sham operation but no appearance of mitotic figures. A similar but more
      prolonged increase in TK occurred in the arterialized transplant group with the
      highest levels recorded on day 4. The level remained significantly elevated above
      pre-operative until 10 days and declined within 20 days. Mitotic figures appeared
      at 2 days, reached significance at 7 and 10 days and had disappeared by 20 days.
      The pattern of changes was accentuated in animals in which the artery was not
      reanastomosed and the increases in TK and AAT were still significant at 20 days.
      Whilst similar degrees of peri-portal cellular infiltrate occurred in both groups
      of rats, bile duct proliferation was most obvious in non-arterialized
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155588
TI  - The effects on liver metastases of circadian patterned continuous hepatic artery
      infusion of FUDR.
AB  - Although continuous hepatic artery infusions (CHAI) of (FUDR) Floxuridine have
      been effective in reducing the size of colorectal hepatic metastases the toxicity
      of the infusions have been high with almost a quarter of the patients developing
      biliary sclerosis. Techniques to lower toxicity, yet continue the beneficial
      antitumor effects, are being investigated. One suggested strategy is to change
      the flow pattern of the continuous infusion from a constant rate to a day cycled
      pattern. In this infusion a continuous rate is given over a 24 hour period with
      60% of the infusion delivered between 3 PM and 9 PM and the least amount of
      infusion delivered between 3 AM and 9 PM. Previous research has suggested that
      this day cycle pattern will lower the toxicity of the infusion. This experiment
      is a test of "day cycled" continuous hepatic artery infusions in rats bearing
      hepatic metastases from a colon adenocarcinoma. Previous research from our
      laboratory has shown a lowered toxicity when the constant infusion was replaced
      with the day cycled pattern. In the present study 10 rats with hepatic
      adenocarcinoma metastases were placed on constant CHAI of FUDR at 10mg/kg/day for
      14 days. There was an 80% mortality from chemotherapy toxicity and a 90%
      objective response rate. Nine other rats were treated with "day cycled" CHAI of
      FUDR at 15mg/kg/d. There was no mortality in this group and the objective
      response rate was 90% as in the previous group. This study demonstrated that "day
      cycled" CHAI of FUDR was substantially less toxic and that the antitumor effect
      was identical to the constant infusion.

PMID- 8155589
TI  - Traumatic duodenal rupture and avulsion of the ampulla of Vater.
AB  - Duodenal injury following blunt abdominal trauma is uncommon. The severity of
      injury can vary from an intramural haematoma to a duodenal rupture with
      associated transection of the pancreatic duct. A case of duodenal rupture with
      avulsion of the ampulla of Vater is presented and discussed.

PMID- 8155590
TI  - Duodenal web and pancreas divisum causing pancreatitis in an adult.
AB  - Duodenal malformations are the third commonest cause of intestinal obstruction in
      infants. A spectrum of intrinsic obstructive lesions within the duodenum ranges
      from atresia to congenital bands. Rarely, duodenal malformations may first
      present in adulthood. Less than 70 cases of duodenal web presenting in an adult
      have been reported in the literature. In 10 patients the presentation was
      associated with pancreatitis. We report a case of congenital duodenal web
      associated with pancreas divisum which first presented in an adult with the
      clinical characteristics of recurrent acute pancreatitis.

PMID- 8155591
TI  - Beware the anomalous portal vein.
AB  - Portal vein thrombosis is an unusual potential complication of liver resection.
      In our case it was due to ligation of the right branch of the portal vein during
      right hepatectomy in a patient without portal vein bifurcation. Hepatic
      angiography can delineate this abnormality and influence the choice of surgical
      management.

PMID- 8155592
TI  - Intrahepatic biliary cystadenoma with intracystic gallstone formation.
AB  - Biliary cystadenoma is a rare tumor of the liver. We describe a biliary
      cystadenoma of the left lobe of the liver with intracystic gallstone formation.
      This is the first report of stone formation in biliary cystadenoma of the liver.

PMID- 8155593
TI  - Liver trauma: new management trends.

PMID- 8155594
TI  - Budd-Chiari syndrome: shunt or transplant?

PMID- 8155595
TI  - The Ca2+/calmodulin-activated, phosphoprotein phosphatase calcineurin is
      sufficient for positive transcriptional regulation of the mouse IL-4 gene.
AB  - We have studied the TCR mediated signal transduction pathways involved in
      transcriptional regulation of the mouse IL-4 gene. The sequences extending from
      base pair -766 to +63 of the IL-4 gene were inserted upstream of a luciferase
      indicator gene. Transcriptional activity was observed when the construct, [pIL-4(
      766)], was transfected into either the IL-4 producing cell line, EL-4, or the IL
      4 non-producing T cell hybridoma, 68-41, but not in the L929 fibroblast cell
      line. By analysis of deletion mutants of pIL-4(-766), we identified a
      transcriptional regulatory element that is tightly associated with a signal
      coming from the TCR and which controls inducible activation of the IL-4 promoter.
      By analysis of deletion mutants of pIL-4(-766), this latter element was found
      between base pairs -147 to -17. Electrophoretic mobility shift assays indicated
      that expression of a nuclear binding protein with binding sites between base
      pairs -84 and -55 could be induced. By competition and mutation analysis, the
      binding motif of this protein was determined to be AAAATTTTCC. Stimulation with
      ionomycin alone was sufficient to induce activity in pIL-4(-766). Cyclosporin A
      inhibited both the IL-4 promoter activity and activation of the inducible nuclear
      protein. Transient over-expression of a constitutively active form of the
      Ca2+/calmodulin-regulated protein phosphatase, calcineurin was sufficient to
      cause activation of pIL-4(-766) without any additional stimulus. These results
      indicate that the signaling requirements for activation of upstream positive
      regulatory elements of the IL-4 gene are distinct from those of the IL-2 gene.
      Ca2+ mobilization is sufficient to activate the IL-4 promoter, whereas IL-2 gene
      transcription requires both Ca2+ mobilization and protein kinase C activation.

PMID- 8155596
TI  - IL-2 promoter-driven lacZ expression as a monitoring tool for IL-2 expression in
      primary T cells of transgenic mice.
AB  - A transgenic mouse system has been established to follow the pattern of IL-2
      expression at the level of single T cells. This was achieved by introducing a
      human IL-2 promoter-driven reporter gene (Escherichia coli lacZ) into the
      germline of mice and monitoring its product, beta-galactosidase (beta-gal), by
      FACS analysis. Ex vivo experiments confirmed that the regulated expression of the
      transgene is comparable with that of the endogenous IL-2 gene. Transgene
      expression is inducible by mitogens, restricted to T cells, and diminished by
      immunosuppressive agents, such as cyclosporin A, at concentrations known to
      suppress IL-2 transcription. Depending on the mitogens used, 30-50% of peripheral
      T cells produced IL-2 with an asynchronous induction pattern, as measured by
      transgenic beta-gal activity. Both helper (CD4+CD8-) and cytotoxic T cells (CD4
      CD8+) respond with comparable heterogenous expression levels but they show
      different frequencies of beta-gal production. Transgenic beta-gal-producing T
      cells were detectable as early as 2 h after mitogen stimulation. These cells
      represent a transitional IL-2 secreting, IL-2 receptor alpha-chain negative T
      cell population, which occurs in the autocrine process of T cell activation.
      Administration of staphylococcal enterotoxin A (SEA), a bacterial superantigen,
      resulted in a T cell specific (Thy-1.2) increase (2.5-fold) of reporter gene
      expression in vivo. In summary, we could demonstrate that IL-2 promoter-driven
      reporter gene expression in transgenic mice is a sensitive tool to characterize
      IL-2 expressing cells phenotypically.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155597
TI  - Identification of two binding sites in staphylococcal enterotoxin B that confer
      specificity for TCR V beta gene products.
AB  - The enterotoxins produced by Staphylococcus aureus are potent mitogens. They
      stimulate T cells in an oligoclonal fashion that is dependent on the expression
      of particular variable region gene elements in the beta-chain of the TCR (V
      beta). The fourth hypervariable loop of the TCR beta-chain is generally regarded
      as the site of contact for both viral and microbial superantigens. Recently,
      residues 60 and 61 of staphylococcal enterotoxin B (SEB) have been highlighted as
      central to the interaction of this toxin with the TCR. We have, therefore,
      analysed a series of toxins with mutations at these positions to investigate how
      amino acid substitutions affect the ability of mutant toxins to stimulate both
      human and mouse T cells. Each of the variant toxins induced proliferation in a
      murine V beta 8.3 T cell clone, whereas a V beta 8.1 T cell clone only responded
      to native toxin. A panel of nine human T cell clones expressing six different V
      beta elements, all of which responded to native SEB, was tested for reactivity to
      the variant toxins. Only one V beta 19.1+ T cell clone was found to be sensitive
      to substitution at positions 60 and 61 in a manner analogous to the murine V beta
      8.1 T cell clone. Semi-quantitative analysis of the TCR V beta expression of
      human T cell lines expanded with native and mutant SEB revealed that none of the
      variant toxins could stimulate T cells that expressed V beta 19.1. Taken
      together, these results suggest that the interaction of mouse V beta 8.1 and
      human V beta 19.1 TCRs with SEB differs from other TCRs. Sequence comparisons of
      the different TCR V beta chains indicated that residues in the second
      complementarity determining region (CDR2) interact with the 60-61 loop of SEB.
      Therefore, a minimum of two distinct binding modules confer specificity to the
      interaction of the TCR with SEB.

PMID- 8155598
TI  - Allelic polymorphism in the coding region of human TCR C alpha gene and
      characterization of structural variability in the alpha chain constant domain.
AB  - An allelic variant of the human TCR C alpha gene, designated C alpha AL, which
      encodes a structurally different protein product has been characterized. C alpha
      AL was independently sequenced using polymerase chain reaction (PCR)-amplified
      TCR C alpha cDNA from various T cell clones derived from a same individual. It
      differed from the most usual C alpha sequence by two non-synonymous base changes
      at codons 4 (AAC-->AAG) and 84 (GAA-->GCA) of the C alpha coding region. These
      changes imply amino acid substitutions Asn-->Lys and Glu-->Ala respectively. An
      oligotyping method, based on hybridization of allele-specific oligonucleotides to
      PCR-amplified C alpha DNA, is also described. It was used for differential typing
      of the two C alpha forms in family and population studies. In each of three T
      cell clones analyzed from the same donor having two rearranged TCR alpha chain
      transcripts, C alpha AL was found in only one of the transcripts. In addition, C
      alpha AL segregated as a co-dominant mendelian allele within the family of this
      donor. Population analysis was carried out in 73 spanish individuals. Twelve
      donors (16.4%) were heterozygous, implying that C alpha AL was present in this
      population sample with an allelic frequency of 0.08. The observed frequencies of
      C alpha genotypes were those expected for the two alleles being in Hardy-Weinberg
      equilibrium. This demonstration of structural polymorphism in the constant region
      of TCR alpha chains provides a useful genetic marker for TCR and disease
      association studies due to its precise mapping within the C alpha coding region,
      and its significant frequency in the analyzed population.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8155599
TI  - Phenotype and TCR gamma delta variable gene repertoire of intestinal
      intraepithelial lymphocytes in wild mice (Mus musculus domesticus): abundance of
      V gamma 1 transcripts and extensive delta gene diversity.
AB  - In order to study murine intestinal intraepithelial lymphocytes (IEL) independent
      of factors imparted by conditions of laboratory housing and breeding, and to
      provide a basis for comparison of IEL studies between inbred and outbred mouse
      populations, IEL from the domestic house mouse, Mus musculus domesticus, were
      analyzed by flow cytometric analyses using mAbs to murine lymphocyte markers, and
      by polymerase chain reaction to study the TCR gamma and delta V gene repertoires.
      The majority of IEL in wild mice were CD3+, CD8+CD4- T cells. CD4+CD8- also were
      present in IEL isolates from wild mice, although at low numbers. Among IEL, but
      not T cells from the spleen or lymph nodes, there was a notable lack of Thy-1
      expression, a preponderance of CD8 alpha alpha + T cells, and a relatively high
      ratio (3:1) of TCR gamma delta + T cells over TCR alpha beta + T cells,
      suggesting that some IEL in wild mice may develop via an extrathymic pathway
      similar to that described for laboratory mice. Analyses of the IEL gamma and
      delta variable genes revealed rearrangements of three of six V region gamma genes
      (V gamma 1, V gamma 2, and V gamma 5), with an abundance of V gamma 1 transcripts
      as determined by Northern blot analyses. For the delta gene, rearrangement of
      five of seven V region elements had occurred (V delta 2, V delta 3, V delta 4, V
      delta 5, and V delta 6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155600
TI  - A thymic epithelial cell line induces both positive and negative selection in the
      thymus.
AB  - TCR engagement in the thymus results in both survival and elimination signals for
      developing thymocytes. To examine whether both signals can be provided by the
      same cell type, we investigated the ability of a thymic epithelial cell (TEC)
      line 427.1, previously shown to allow positive selection in the thymus, to induce
      clonal deletion of immature thymocytes. [H-2b/s-->H-2s] bone marrow chimeras are
      non-responsive to antigens in the context of H-2b. However, chimeras that
      underwent intrathymic injection of H-2b/s 427.1 cells expressing vesicular
      stomatitis virus (VSV) nucleocapsid antigen acquired the ability to raise
      influenza, but not VSV specific H-2b restricted cytotoxic T lymphocyte (CTL)
      responses. The ability of 427.1 cells to delete CD4+CD8+ thymocytes was
      determined using mice transgenic for the TCR specific for ovalbumin (OVA) in the
      context of H-2Kb. OVA transfected, but not mock transfected 427.1 TECs, induced
      in vitro deletion of CD4+CD8+ TCR transgenic thymocytes manifested as a down
      modulation of CD4 and CD8 molecules, a shift in the side versus forward scatter
      characteristics of thymocytes, and appearance of thymocytes with subdiploid
      content of DNA indicated the ongoing process of DNA fragmentation. The finding
      that the same TEC line is capable of inducing both positive and negative
      selection in the thymus suggests that thymocytes bearing TCRs specific for self
      peptides expressed by positively selecting thymic epithelium can be deleted.
      Therefore the expression of a unique set of MHC associated peptides by TECs does
      not appear to be the basis for the positive outcome of the TCR ligation on
      immature thymocytes.

PMID- 8155601
TI  - Functional recognition of in vivo processed self antigen.
AB  - C5, the fifth component of complement, is a circulating self protein which
      induces complete tolerance in MHC class II restricted, CD4+ T cells due to the
      presentation of C5 taken up from plasma. Functional recognition of in vivo
      processed C5 was monitored by activation of C5 specific T cell hybrids cultured
      with antigen presenting cells (APC) from C5 expressing mice. Dendritic cells
      isolated from various tissues (spleen, thymus, skin) proved to be the most
      efficient APC, since 10- to 50-fold more macrophages and at least 100- to 500
      fold more B cells were needed to achieve similar T cell activation. Stimulatory
      C5 peptide--class II complexes generated in vivo were retained on the surface of
      dendritic cells but not on macrophages and B cells upon prolonged culture.
      Dendritic cells but not macrophages from thymus presented in vivo processed C5.
      Taken together these findings emphasize the crucial role dendritic cells play for
      recognition of soluble self proteins by MHC class II restricted T cells.

PMID- 8155602
TI  - HLA-B*3501-peptide interactions: role of anchor residues of peptides in their
      binding to HLA-B*3501 molecules.
AB  - Two HLA-B*3501 binding self-peptides, LPFDFTPGY (37F) and LPGPKFLQY (28H), were
      isolated from HLA-B*3501 molecules expressed by cultured human B lymphoid cells.
      Both sequences were consistent with previously reported motifs of HLA-B*3501
      binding peptides which carry proline at position 2 and tyrosine at position 9 as
      anchor residues. Direct binding of these peptides to HLA-B*3501 molecules was
      quantitated by flow cytometry analysis of RMA-S cells. transfected with the HLA
      B*3501 gene (RMA-S-B*3501). Both 37F and 28H peptides bound effectively to HLA
      B*3501 molecules. Substitution of amino acids at position 2 and/or 9 of HLA
      B*3501 binding peptides markedly reduced their binding to HLA-B*3501 molecules.
      These results indicate that two anchor residues, proline at position 2 and
      tyrosine at position 9 are critical in binding of peptides to HLA-B*3501
      molecules. Insertion of up to four glycine residues at position 8 of the peptide
      37F did not affect its binding affinity to HLA*3501 molecules. These results
      indicate that long peptides can effectively bind to HLA class I molecules
      provided that anchor residues are conserved.

PMID- 8155603
TI  - Phosphatidyl inositol-linked forms of a murine class I MHC molecule expressed on
      Chinese hamster ovary cells retain peptide binding capability and alloreactivity.
AB  - A gene encoding a phosphatidyl inositol-linked form of the murine class I MHC
      molecule H-2Kd was constructed and the protein expressed in Chinese hamster ovary
      cells together with murine or human beta 2-microglobulin (beta 2m). The resulting
      lipid-linked class I heterodimers can be efficiently converted into a soluble
      form by treatment of transfected cells with a phospholipase. Cells expressing Kd
      heterodimers were characterized with respect to heavy chain levels at the cell
      surface, peptide binding, and recognition by Kd-specific antibodies and
      alloreactive cytotoxic T cells. All transfectants bound a 3H-labeled Kd
      restricted nonamer peptide, although more peptide bound to cells expressing the
      Kd/human beta 2m combination, perhaps because of a greater number of empty
      molecules at the cell surface. A dissociation constant of 5 x 10(-8) M derived by
      Scatchard analysis is within the range expected for interactions of peptides with
      class I MHC molecules. Alloreactive cytotoxic T cells which recognize wild-type
      Kd on murine cells lysed the hamster cells expressing lipid-linked Kd without
      regard to the species of the beta 2m light chain. These results indicated that
      the engineered lipid-linked Kd molecule is expressed at the cell surface, is
      recognized by antibodies and T cells, and functions to bind peptide.

PMID- 8155604
TI  - Transforming growth factor-beta regulates normal human pre-B cell
      differentiation.
AB  - Light chain gene rearrangement during mammalian pre-B differentiation generally
      occurs in an orderly manner, beginning with kappa genes and proceeding through
      lambda genes. We have previously shown that human pre-B cell differentiation in
      vitro leads to a skewing toward lambda expression, resulting in a higher
      percentage of lambda+ cells than kappa+ cells. We now report that the
      multifunctional polypeptide transforming growth factor-beta (TGF-beta) exerts a
      selective inhibitory effect on the acquisition of cell surface lambda light
      chains during in vitro differentiation of normal human pre-B cells, giving rise
      to a balanced ratio (approximately 1:1) of kappa+ to lambda+ cells that resembles
      what normally exists in vivo. The TGF-beta effect was ablated using a
      neutralizing anti-TGF-beta antiserum and TGF-beta had no significant effect on
      the acquisition of kappa or surrogate light chains. Experiments using highly
      enriched pre-B cells (90-95% cytoplasmic mu+) suggested that the TGF-beta effect
      was directly on the pre-B cell or the pre-B cell to mu+/lambda+ immature B cell
      transition. The following peptides, cytokines, and antibodies had no effect on
      light chain acquisition or expression: substance P, vasoactive intestinal
      peptide, leu/met enkephalin, IL-1, IL-4, IL-7, anti-class II MHC, anti-CD24, anti
      CD40, and the CD10 inhibitor phosphoramidon. A selective regulatory role for TGF
      beta on normal human B cell development in the bone marrow microenvironment is
      suggested by these results.

PMID- 8155605
TI  - Alternatively spliced MHC class I mRNAs show specific deletion of sequences
      encoding the extracellular polymorphic domains.
AB  - Analysis of structural diversity at the 5' end of H-2 class I mRNAs showed that a
      small fraction of Kd mRNA from L1210 lymphoma (approximately 10%) or from various
      normal tissue (2-3%) of DBA/2 mice carries a precise deletion of the sequences
      encoding the second extracellular domain. Nucleotide sequence of the coding
      region of the second domain-lacking Kd mRNA was found to be identical to the
      known sequence of the Kd gene from DBA/2 liver with the exception of the above
      deletion and a single nucleotide silent substitution at position 150, suggesting
      that the novel Kd RNA is a product of the functional Kd gene. In addition,
      various normal tissues that are known to express varying levels of Kd antigen did
      not show changes in the expression levels of the second domain-lacking Kd mRNA
      thus ruling out the possibility that synthesis of this RNA is coupled to control
      the expression levels of the canonical Kd mRNA, hence the Kd antigen. Analysis by
      polymerase chain reaction showed that all normal tissues including the testis and
      sperm express this RNA. Preliminary analysis of the Kb mRNA from the spleen and
      thymus of C57BL/6 mouse also showed the presence of second domain-lacking Kb mRNA
      in these mice. Furthermore, preliminary structural analysis of the Dd and Ld
      mRNAs has revealed additional polymorphic extracellular domain-lacking mRNA
      species including a first domain-lacking Dd mRNA and two Ld mRNAs that lack
      sequences encoding either the first extracellular domain or the second
      extracellular domain respectively. These results together show that H-2 mRNAs
      lacking sequences that specify individual extracellular polymorphic domains are a
      frequent feature of the structural diversity at the 5' ends of these mRNAs.
      Potential significance of these domain-lacking H-2 mRNAs is discussed,
      particularly with regard to the function of the putative encoded peptides as
      targets of natural killer cells.

PMID- 8155606
TI  - Non-obese diabetic (NOD) mice display enhanced immune responses and prolonged
      survival of lymphoid cells.
AB  - We report that lymphoid cells originating from the non-obese diabetic (NOD)
      autoimmune prone mouse strain are resistant to several signals known to induce
      programmed cell death. In vitro culturing of lymphoid cells of splenic or lymph
      node origin showed that B cells and T cells of both CD4+ and CD8+ phenotypes from
      NOD mice display extended survival in vitro. By cytofluorimetric analysis,
      immature CD4+ CD8+ NOD thymocytes were shown to partially resist in vivo
      treatment with corticosteroids. Finally, immunization with protein antigens
      induced enhanced and prolonged immune responses in NOD mice compared with normal
      C57BL/6, BALB/c, and C3H/Tif control mice. We conclude that the NOD mouse
      displays a defect in the mechanism(s) mediating programmed cell death in T and B
      lymphocytes. These findings provide a novel explanation for the B cell
      aberrations observed in the NOD mouse and may have implications for the
      understanding of the autoimmune pathogenesis in this mouse strain.

PMID- 8155607
TI  - Effect of polyurethane surface chemistry on its lipid sorption behavior.
AB  - The relationships among surface, bulk properties and lipid sorption behaviors of
      segmented polyurethanes (SPUs) with various polyol soft segments were
      investigated. The polyols used in this study were poly(ethylene oxide) (PEO),
      poly(tetramethylene oxide) (PTMO), and poly(dimethylsiloxane) (PDMS). The hard
      segment of these segmented polyurethanes was composed of 4,4'-diphenylmethane
      diisocyanate and 1,4-butanediol, present at 50 wt%. X-ray photoelectron
      spectroscopic (XPS) and dynamic contact angle measurements were carried out in
      order to analyze the surface chemical structure in the air- and water
      equilibrated states. XPS revealed that in the air-equilibrated state, lower
      surface free energy components were enriched at the air-solid interface, whereas
      in the water-equilibrated state, higher surface free energy components were
      enriched at the water-solid interface. The change in environment from air to
      water induced the surface reorganization in order to minimize interfacial free
      energy. Lipid sorption behaviors of SPUs were investigated by means of infrared
      spectroscopy. Even after extensive rinsing of the surface, the amount of lipid
      present on the SPU surface was more than that calculated on the assumption that a
      monolayer covers the SPU surface. Therefore, the lipid was not only adsorbed on
      the surface of SPU but absorbed into SPU. The SPU with hydrophilic PEO sorbed
      larger amount of phospholipid compared with that with hydrophobic polyol such as
      PTMO and PDMS. Also, the competitive sorption behaviors of phospholipid and
      cholesterol from their mixed liposome solution were studied. The ratio of sorbed
      cholesterol to phospholipid increased with an increase in surface hydrophobicity
      owing to the hydrophobic nature of cholesterol.

PMID- 8155608
TI  - In vitro activation of human macrophages by alginate-polylysine microcapsules.
AB  - Microencapsulated islets of Langerhans have been proposed as a bioartificial
      pancreas. However, foreign body reaction with fibrosis has been observed around
      implanted microcapsules. Since macrophages are present in this reaction and
      interleukin-1 (IL-1), a cytokine released by activated macrophages, may induce
      fibrosis, we tested the capacity of alginate-polylysine microcapsules to activate
      macrophages. Human monocytes were isolated from whole blood of healthy donors by
      a Ficoll density gradient and adherence to a plastic support. Monocytes were
      cultured for 24 h with: (1) alginate-polylysine microcapsules; (2)
      lipopolysaccharide (LPS) (positive control group); and (3) alone (negative
      control group). Monocyte activation was evaluated by measuring the secretion of
      IL-1 beta and the production of intracellular IL-1 alpha and IL-1 beta.
      Macrophages characterization was performed by immunocytological subtyping. IL-1
      beta release and intracellular IL-1 beta and IL-1 alpha production were
      significantly higher when macrophages were cultured with alginate-polylysine
      microcapsules than when macrophages were cultured alone. In conclusion,
      macrophages are activated in vitro by alginate-polylysine microcapsules. This
      effect may be involved in the fibrosis observed in vivo around implanted
      microcapsules. In addition, interleukin-1, released during macrophage activation,
      may cross the microcapsule membrane and impair islet function.

PMID- 8155609
TI  - The effect of plasma-induced graft copolymerization of PHEMA on silicone rubber
      towards improving corneal epithelial cells growth.
AB  - A PHEMA grafted polymer film was prepared by plasma induced graft
      copolymerization onto an elastic material, silicone rubber. The control, Ar
      plasma-treated, and PHEMA-grafted silicone rubber surfaces were characterized by
      ESCA, FTIR-ATR, and SEM techniques. ESCA verified the respective chemical shift
      of control and Ar plasma-treated films. The presence of the grafted PHEMA was
      also verified by ESCA. The amounts of grafted PHEMA did not monotonously increase
      with the plasma exposure conditions, but decreased after passing a maximum. The
      introduction of PHEMA onto a hydrophobic support provided an adequate surface for
      rabbit corneal epithelium cell attachment and growth. Cell attachment and growth
      onto these surfaces were examined by light microscopy. Cell attachment onto the
      control and Ar plasma-treated surface was negligible, while improved attachment
      and growth of rabbit corneal epithelium cells was demonstrated on the PHEMA
      grafted polymer surface. The PHEMA-grafted silicone rubber surface demonstrated a
      confluent cell layer after 72 h.

PMID- 8155610
TI  - The bone-cement interface: histological observations on the interface of cemented
      arthroplasties within the immediate and late phases.
AB  - Undecalcified specimens of cemented arthroplasties obtained during the early and
      late phases were studied. On the tenth postoperative day, there was excellent
      interlocking of the cement with the soft and hard tissues of the bone: there was
      no necrosis of the bed of the implant: a neutrophilic and macrophagic
      inflammatory response, where present, was mild and focal. Samples of the bone
      cement interface of well fixed components obtained (at autopsy or by biopsy) many
      years after implantation revealed a thin and quiescent fibrous interfacial
      membrane alternating with bone and osteoid (that is, segmental osseointegration)
      or a cartilaginous layer abutting on the cement. It is concluded that, firstly,
      modern cementation techniques are not associated with extensive necrosis of the
      underlying bone in the immediate postoperative period; secondly, monomeric and
      polymeric methylmethacrylate as such is not toxic to the tissues; and, thirdly,
      acrylic cement is osseointegrated when motion at the interface is at its minimum.

PMID- 8155611
TI  - Infrared spectral analysis of extractables from poly(etherurethane urea) (PEUU)
      elastomers.
AB  - Poly(etherurethane urea) (PEUU) elastomers when employed as biomedical devices
      may be susceptible to extraction upon implantation. Four PEUU elastomers
      containing a single PEUU formulation, but varying in terms of their additives,
      were subjected to an in vitro extraction procedure. The additives in the PEUUs
      were Methacrol 2138 F at 5 wt% and Santowhite powder at 1 wt% levels. Only 1-2
      wt% of the PEUUs was extractable with methanol. Fourier transform infrared
      spectroscopy (FT-IR) furnished qualitative and quantitative information on the
      extractables. The extractables consisted of a PEUU component that on the average
      was richer in soft segment than the bulk PEUU, and the two additives, Methacrol
      2138 F and Santowhite powder.

PMID- 8155612
TI  - Effect of sulfated polysaccharides on hepatocyte adhesion.
AB  - The effects of sulfated polysaccharides on hepatocyte adhesion on the polystyrene
      dish and fibronectin-coated dish were investigated. Dextran sulfate and synthetic
      mannopyranan sulfate slightly inhibited hepatocyte adhesion on fibronectin-coated
      dish, while heparin showed no effect. On the other hand, hepatocyte adhesion on
      polystyrene dishes was stimulated in the presence of sulfated polysaccharides in
      the medium.

PMID- 8155613
TI  - [The role of medical periodicals].

PMID- 8155614
TI  - [Color vision in diabetics].
AB  - Color perception is often already altered even if the ocular, anatomic and
      functional exams maintain their results within the normal limits. This fact is
      more important in diabetes, where chromatic abnormalities exist at half of the
      subjects, even if they do not reveal any signs of diabetic retinopathy. The
      authors present some of the methods in clinical exam of color perception, the
      characters of dyschromatopsia and glycemic self control using the method of
      coloured bandelets, types of dyschromatopsia which may appear during the
      evolution of the diabetes, and also the predictive effect of dyschromatopsia for
      the appearance of diabetic retinopathy.

PMID- 8155615
TI  - [The visual prognosis in congenital cataract].
AB  - The authors focus on the evolution of visual function postoperatorial, based on
      349 patients which where diagnosed and operated by congenital cataract, during
      1973-1992, in Tg. Mures Ophthalmological Clinic. All the interventions were done
      by discising the anterior capsula and washing the lens masses. After studying
      these cases, the authors conclude that visual prognosis of the operated eye
      depends on the presence of other congenital abnormalities, on the age of the
      patient and on the intervention type. In spite of all surgical progresses,
      congenital cataract still stands as an affection with reserved functional
      consequences.

PMID- 8155616
TI  - [Cystic-structure echographic imaging in retinal detachment].
AB  - The B-type echographic exam in retinal detachment shows in the most accurate way
      the detached retina. In the total detachments the aspect reproduced the V-image,
      because in the perpendicular section, the retinal folds join at the papilla. By
      the rotation of the transducer, when the oblique echographic section get close to
      the perpendicular section, it may be moved on the monitor like two heterogeneous
      planes or like a chistic echographic image in the vitreous. This show the
      importance of the chistic echographic image in the differential diagnosis of the
      retinal detachment.

PMID- 8155617
TI  - [Malignant choroidal melanoma with secondary invasion of the sclera].
AB  - The melanoma of the choroid is a tumour very rich in cells, with a reduced
      stroma. The reticular fibres and the pigmentation vary in abundance from one
      tumour to another and even from one area to another of the same tumour. The
      tumour vascularization is achieved by incompletely developed vessels with
      endothelium wall only, or by simple vascular lacunae in direct contact with
      tumoral cells, having various arrangements: tubular, in palisade, with lobular
      structure or in pseudo-rosettes. The great degree of malignity of the tumour and
      its different histopathological aspects connected with the possibility of
      intraorbital development and of metastasis, which impose early diagnosis and
      therapy, made us to present these observations.

PMID- 8155618
TI  - [The surgical results in rhegmatogenous retinal detachment].
AB  - The paper present the functional and anatomic results obtained in 376 retinal
      detachment operations done in the Ophthalmological Clinic from Cluj-Napoca. The
      following types of operations were done: cerclage Arruga, scleral indentation,
      surface diathermy, laser photocoagulation. The retrospective study revealed
      percentages of 73.41% the anatomic reapplication and 50% in functional recovery.
      The negative influencing factors of the prognosis were: aphakia, large and old
      retinal detachments, macular region affectation.

PMID- 8155619
TI  - [Diagnostic methods in retinal detachment].
AB  - Important diagnosis methods are anamnesis, visual acuity determination, visual
      field determination, anterior segment biomicroscopy, tonometry, gonioscopy. Great
      attention must be paid to the ophthalmoscopy with scleral indentation. The paper
      compare the advantages and disadvantages of direct ophthalmoscopy using Goldmann
      contact lens. A great importance has the graphical representation of the eye
      fundus pathology, and also applying Lincoff rules in the localisation of the
      retinal breaks in retinal detachment. As special methods in examination are
      revealed the diaphanoscopy, the angiofluorography, the computerized tomography,
      the tomography in magnetic resonance field, and also the utilization of the
      electrophysiological and echographic exams in retinal detachment diagnosis.

PMID- 8155620
TI  - [The criteria for echographic diagnosis in retinoblastoma].
AB  - The paper present an echographic survey on 27 pathological eyes suspected to
      present retinoblastoma, investigated with the same devices and by the same
      investigator. The diagnosis of retinoblastoma has been echographically put on 13
      eyes. We haven't noticed any error on the investigated set since the diagnosis
      was histopathologically confirmed on 11 eyes. 2 eyes were not enucleated because
      they had before the enucleation of the contralateral ocular globe. It is
      discussed the utility of the echographic investigation for the positive and
      differential diagnosis of the retinoblastoma.

PMID- 8155621
TI  - [Ocular lesions produced by caterpillars].
AB  - The caterpillars' tissues contain substances for the stein, mucous membranes and
      eyes. The paper presents 2 clinical investigations of ocular lesions produced by
      caterpillars. The first was done on a 7-year-old child who has got toxic
      keratoconjunctivitis and erythematosus and vesicular type pruriginous cutaneous
      eruption after crashing of a caterpillar, because of its specific toxin. The
      phenomena diminish after large ocular washings, and the cutaneous toxic phenomena
      retrocead after antipruriginous lotions and general administration of
      antihistaminics. The later investigation was done on a 17-year-old patient with
      toxic iridocyclitis and fibrinous dense exudate due to caterpillar's hair. The
      anatomopathological exam of the iris showed lymphoplasmocitary infiltrate with
      many eosinophils. The ocular inflammation was due to caterpillar's hair presence
      in the anterior chamber and also to the toxin freed. The hair elimination from
      the anterior chamber determined the cure of the disease.

PMID- 8155622
TI  - [Trauma to the posterior eye segment].
AB  - The paper presents 113 patients with posterior ocular segment injuries
      hospitalized in a five years period, at the Department of ophthalmology Craiova;
      they represent 9.3% of ocular injuries and 0.85% of all the patients hospitalized
      in that period. 81 cases (71.68%) represents posterior ocular contusions, 25
      cases (22.12%) represents posterior scleral plaies, and 7 (6.19%) cases
      represents optic nerve injuries. The functional results depends of
      anatomicoclinical types of lesions, and of the rapidity of instituation the
      treatment.

PMID- 8155623
TI  - [The ultramicroscopic aspects in malignant choroidal melanoma].
AB  - The survey focuses on the observation using the electronic microscope of two
      cases of uveal malignant melanoma. The ultrastructure of the cellular population
      which from this type of malignant tumour was followed, mentioning both the common
      and the particular aspects. The nuclear and nucleolar modifications, indicating
      an increase degree of atypia for the epithelioid cells compared with the fusiform
      cells, were observed. Some aspects of the abnormal tumoural cells were also
      emphasized. We noticed in the structure of the tumours, besides the tumoural
      cells, another structure of non-tumoural macrophage and reticular cells, and we
      described their ultrastructure.

PMID- 8155624
TI  - [The therapeutic effect of acyclovir in herpetic keratitis].
AB  - In Ophthalmological Clinic of the District Bucharest Hospital, the authors
      studied 59 patients with herpetic keratitis, and keratouveitis treated with
      Zovirax (acyclovir). They try to prove with clinical arguments the efficacity of
      this treatment in different forms of herpetic keratitis. The authors consider the
      acyclovir like the election therapy of ocular herpes, because it determines the
      increase of ocular vision in almost cases with short average hospitalization.

PMID- 8155625
TI  - [Eye surgery, surgery with an increased degree of difficulty].

PMID- 8155626
TI  - [Visual acuity study in the child 18 months to 2 years old].
AB  - Visual acuity for a child may be determined using objective instrumental methods
      (especially for children under 18 months) or using clinical examination at the
      optotype--subjective methods (for children after 18 months). The use of 2 or 3
      different optotypes, which are attractive for children, is necessary because of
      their great capacity of memorizing the tests. The author presents a personal
      optotype model, with seven different images, which have to be recognized by the
      children from a distance of 2.5 m.

PMID- 8155627
TI  - Competition between Li+ and Mg2+ for the phosphate groups in the human
      erythrocyte membrane and ATP: an NMR and fluorescence study.
AB  - We investigated the mechanism of competition between Li+ and Mg2+ in Li(+)-loaded
      human red blood cells (RBCs) by making 7Li and 31P NMR and fluorescence
      measurements. We used 7Li NMR relaxation times to probe Li+ binding to the human
      RBC membrane and ATP; an increase in Mg2+ concentration caused an increase in
      both 7Li T1 and T2 values in packed Li(+)-loaded RBCs, in suspensions of Li(+)
      loaded RBC ghosts, in suspensions of Li(+)-containing RBC membrane, and in
      aqueous solutions of ATP, indicating competition between Li+ and Mg2+ for binding
      sites in the membrane and ATP. We found that increasing concentrations of either
      Li+ or Mg2+ in the presence of human RBC membrane caused an increase in the 31P
      NMR chemical shift anisotropy parameter, which describes the observed axially
      symmetric powder pattern, indicating metal ion binding to the phosphate groups in
      the membrane. Competition between Li+ and Mg2+ for phosphate groups in ATP and in
      the RBC membrane was also observed by both fluorescence measurements and 31P NMR
      spectroscopy at low temperature. The ratio of the stoichiometric binding
      constants of Mg2+ to Li+ to the RBC membrane was approximately 20; the ratio of
      the conditional binding constants in the presence of a free intracellular ATP
      concentration of 0.2 mM was approximately 4, indicating that Li+ competes for
      approximately 20% of the Mg(2+)-binding sites in the RBC membrane. Our results
      indicate that, regardless of the spectroscopic method used, Li+ competes with
      Mg2+ for phosphate groups in both ATP and the RBC membrane; the extent of metal
      ion competition for the phosphate head groups of the phospholipids in the RBC
      membrane is enhanced by the presence of ATP. Competition between Li+ and Mg2+ for
      anionic phospholipids or Mg(2+)-activated proteins present in cell membranes may
      constitute the basis of a general molecular mechanism for Li+ action in human
      tissues.

PMID- 8155628
TI  - T.C.G triplet in an antiparallel purine.purine.pyrimidine DNA triplex.
      Conformational studies by NMR.
AB  - The antiparallel purine.purine.pyrimidine DNA triplex, RRY6, which contains a
      T.C.G inverted triplet in the center of the sequence, was examined by proton and
      phosphorous two-dimensional NMR spectroscopy. The local conformation of the T.C.G
      triplet (T4.C11.G18) and the effect of this triplet on the global helical
      structure were analyzed in detail. The formation of the T.C.G triplet is
      confirmed by a set of cross-strand NOEs, including unusual cross-strand NOEs
      between the third strand and the pyrimidine strand as opposed to the purine
      strand of the duplex. NMR data suggest that the T.C.G triplet may be present in
      an equilibrium between a non-hydrogen-bonded form and a T(O4)-C(NH2) hydrogen
      bonded form and that there is a distortion of the in-plane alignment of the three
      bases. The flanking G.G.C base triplets are well-defined on the 5'-side of T4,
      but somewhat interrupted on the 3'-side of T4. The effect of the third strand
      binding on the Watson-Crick duplex was probed by an NMR study of the free duplex
      RY6. NMR parameters are affected mostly around the T.C.G inversion site. The
      perturbations extend to at least two adjacent base triplets on either side. The
      binding of the third purine strand and the accommodation of a central T.C.G
      inversion in RRY6 does not require a readjustment in sugar pucker, which remains
      in the range of C2'-endo. 31P resonances of RRY6 distribute over a range of 2.2
      ppm. The H-P coupling patterns of the third strand differ from those of the
      duplex. General spectral patterns defined by the marker protons of the RRY and
      YRY triplexes are compared.

PMID- 8155629
TI  - Bisulfite induces tandem double CC-->TT mutations in double-stranded DNA. 2.
      Kinetics of cytosine deamination.
AB  - Deamination of cytosine to uracil in double-stranded DNA (ds DNA) by sodium
      bisulfite has been monitored with a sensitive genetic assay. In this system,
      reversion of a mutant in the lacZ alpha gene coding sequence of bacteriophage
      M13mp2 C141 was detected by employing an ung- bacterial strain defective in the
      enzyme uracil glycosylase. Within the 4-base target, it is possible to measure
      the rates of induction of C-->T, C-->A, C-->G, and CC-->TT mutations in DNA that
      has been incubated at physiological temperature and pH and then transfected into
      ung+ and ung- E. coli cells, respectively, for amplification and detection of the
      mutation. For concentrations of bisulfite from 1 to 50 mM, the reversion
      frequency in ung- cells increased linearly with time of incubation. The most
      interesting features of the bisulfite reaction were as follow: (1) Mutations were
      reduced 5-fold in ung+ cells, indicating ung is involved in repair of bisulfite
      treated transforming DNA. (2) Sequencing of 157 revertants revealed that C-->T
      and tandem CC-->TT transition mutations comprised 100% of the mutations scored.
      (3) A unique finding was that, at the highest concentrations and longest
      incubation times, almost every mutant obtained in ds DNA exposed to bisulfite was
      found to be a CC-->TT tandem double mutation. (4) The high frequency of tandem
      double mutants is inconsistent with two random, independent mutational events
      and, coupled with the observed ung dependence, lends support to the concept of
      catalytic deamination, wherein bisulfite induces deamination in contiguous
      cytosines by a concerted mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155630
TI  - Correlations of crystal structures of DNA oligonucleotides with enantioselective
      recognition by Rh(phen)2phi3+: probes of DNA propeller twisting in solution.
AB  - Rh(phen)2phi3+ (phen = 1,10-phenanthroline; phi = 9,10-phenanthrenequinone
      diimine) avidly binds to DNA via intercalation from the major groove and upon
      photoactivation produces strand scission with single base 5' asymmetry.
      Enantiomers of Rh(phen)2phi3+, which lack hydrogen-bonding substituents in
      ancillary positions, distinguish a DNA site through shape-selection; site
      recognition depends upon the local variations in structure at a binding site.
      Here, we examine the application of delta-Rh(phen)2phi3+ as a sequence-dependent
      structural probe and, in particular, as a probe of DNA propeller twisting in
      solution, by comparing directly cleavage results using delta- and lambda
      Rh(phen)2phi3+ on crystallographically characterized oligonucleotides with
      several sequence-dependent crystallographic parameters. The three
      oligonucleotides examined in this study are the Dickerson-Drew dodecamer, 5'
      CGCGAATTCGCG-3', the NarI dodecamer, 5'-ACCGGCGCCACA-3', and the CG decamer, 5'
      CCAACGTTGG-3', all of which have been crystallized in the B-form.
      Enantioselective cleavage and reaction favored by the delta-isomer is found to be
      governed locally by the opening of the site in the major groove. A correlation is
      demonstrated between cleavage by delta-Rh(phen)2phi3+ and the opening in the
      major groove that results from the change in propeller twist (differential
      propeller twist) at a base step. When the major groove is closed as a result of a
      change in propeller twist, there is little cleavage evident by either enantiomer;
      at sites which are indicated crystallographically to be open in the major groove,
      a direct correlation is observed between enantioselective cleavage and the degree
      of opening. A trend of higher enantioselectivity at sites possessing higher twist
      angles is also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155631
TI  - Identification of an amino acid in the ATP binding site of Na+/K(+)-ATPase after
      photochemical labeling with 8-azido-ATP.
AB  - [alpha-32P]-8-N3-ATP, [2-3H]-8-N3-ATP, and non-radioactive 8-N3-ATP have been
      used as photoaffinity probes of the ATP binding site of dog kidney Na+/K(+)
      ATPase. 8-N3-ATP has previously been shown to bind to Na+/K(+)-ATPase with high
      affinity, to be a substrate for Na+/K(+)-ATPase, and to inactivate the enzyme
      upon ultraviolet irradiation [Scheiner-Bobis, G., & Schoner, W. (1985) Eur. J.
      Biochem. 152, 739-746]. 8-N3-ATP competitively inhibits the high-affinity binding
      of [2,8-3H]-ATP to Na+/K(+)-ATPase with a Ki of 3.4 microM, which is comparable
      to the reported KD of 3.1 microM for the binding of 8-N3-ATP to the enzyme. The
      extent of inhibition of ATP hydrolysis by 8-N3-ATP was linearly correlated with
      the stoichiometry of covalent incorporation of 8-N3-ATP into Na+/K(+)-ATPase up
      to about 50% inhibition of activity; however, the linkage between the protein and
      8-N3-ATP was unstable, and the maximum incorporation of 8-N3-ATP was less than
      the nucleotide binding capacity of the protein. After photolysis with ultraviolet
      light, 8-N3-ATP was specifically incorporated into the carboxy-terminal 58-kDa
      fragment of the alpha-subunit of Na+/K(+)-ATPase generated by limited trypsin
      digestion in the presence of KCl, and the beta-subunit was not labeled. 8-N3-ATP
      labeled Na+/K(+)-ATPase was digested with trypsin, and a single peak containing
      the nucleotide was identified after HPLC fractionation of the digest.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155632
TI  - Correlation of ActoS1, myofibrillar, and muscle fiber ATPases.
AB  - Our objective was to determine a good in vitro model for muscle fiber ATPase, and
      we compared the kinetics of Ca(2+)-activated myofibrils and cross-linked actoS1
      in a buffer of physiological ionic strength. The myofibrils were cross-linked
      chemically to mimic the isometric condition of fibers or were un-cross-linked
      (the isotonic condition), and temperature perturbation was used to probe their
      ATPase mechanisms. At 4 degrees C, we have already shown that the kinetics of
      cross-linked actoS1 and myofibrils (cross-linked or not) are similar: there were
      large P(i) bursts and kcat values of about 1 s-1, close to that obtained with
      fibers [Herrmann, C., Sleep, J., Chaussepied, P., Travers, F. & Barman, T. (1993)
      Biochemistry 32, 7255-7263]. So, at 4 degrees C cross-linked actoS1 and
      myofibrils are equally good as models for fiber ATPase. At 20 degrees C, this
      similarity vanishes: progress curves with the myofibrils (cross-linked or not)
      had large P(i) bursts, but with cross-linked actoS1, bursts could not be
      discerned. This shows that at 20 degrees C the predominant steady-state
      intermediates are ATP complexes with actoS1 but are products complexes with the
      myofibrils, as with fibers [Ferenczi, M.A. (1986) Biophys. J. 50, 471-477].
      Further, the kcat values were different: 15.5 s-1 with cross-linked actoS1, 8.3 s
      1 for myofibrils, and 3.5 s-1 for cross-linked myofibrils. With fibers, kcat =
      3.3 s-1. These results show that cross-linked myofibrillar ATPase is a good model
      for muscle fibers contracting isometrically.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155634
TI  - Triple helix formation with short oligonucleotide-intercalator conjugates
      matching the HIV-1 U3 LTR end sequence.
AB  - In an attempt to target short purine sequences in view of pharmacological
      application, we have synthesized three new TFO (triple-helix-forming
      oligonucleotide) conjugates in which an intercalating oxazolopyridocarbazole
      (OPC) chromophore is linked by a pentamethylene linker to a 7-mer oligonucleotide
      matching the polypurine/polypyrimidine sequence located in the HIV-1 U3 LTR end
      region. The TFO moiety of conjugates are 5'CCTTCCC, 5'GGGAAGG, and 5'GGGTTGG.
      Their ability to bind to double-stranded DNA targets was examined. This binding
      is demonstrated by a footprinting technique using DNase I as a cleaving agent.
      The complex involved intermolecular pyr-pur*pyr or pur-pur*pyr triple helix.
      Pyrimidine TFO-OPC binds in a pH-dependent manner, whereas the others do not. The
      formation of the complex has been investigated at neutral pH and increasing
      temperature. We observed that the protection due to the purine and mixed TFO-OPC
      was pH independent and remained identical up to 40 degrees C. To determine the
      position of the OPC chromophore, molecular modeling was undertaken on the purine
      conjugate/target complex. It has been suggested that the complex involved the
      intercalation of the OPC at the triplex-duplex junction with a small unwinding at
      the next excluded site.

PMID- 8155633
TI  - Construction of a synthetic gene for the metalloregulatory protein MerR and
      analysis of regionally mutated proteins for transcriptional regulation.
AB  - The transcriptional control protein MerR is a metalloregulatory switch,
      activating transcription of a mercury resistance operon in the presence of
      mercuric ions and repressing transcription in their absence. We report here the
      construction and utilization of a synthetic merR gene and a single-copy merT'
      lacZ fusion reporter for mutagenic analysis of the MerR protein's function. Site
      directed mutagenesis of clustered acidic residues within the central region of
      the MerR protein indicated that these residues are important to the protein's
      ability to repress transcription. Quadruple or sextuple mutations involving
      residues E83 and E84 and other nearby acidic residues result in a repression
      deficient (RD) phenotype. One of the mutant proteins was purified and shown by
      gel shift assay to retain binding to its operator DNA with an affinity similar to
      wild-type protein, suggesting that transcriptional repression does not correlate
      with MerR binding affinity. A small region of merR corresponding to residues 81
      92 also was mutagenized in a search for other RD mutants and for mutants
      displaying sufficient transcriptional activation in the absence of mercuric ion
      to be classified as constitutive activation (CA) mutants. In this case,
      oligonucleotide-directed randomization of the target region and a
      screening/selection protocol were employed. Sixteen different mutants with an RD
      phenotype were identified, as well as eight different mutants with a CA
      phenotype. A high frequency of S87C mutations is evident in the RD set of
      mutants. The CA mutants have a high incidence of S86C and A89V mutations. The CA
      double mutant S86C/A89V was purified and found to bind to its DNA site with an
      affinity similar to that of the wild-type protein. Chemical nuclease activity
      assays indicate that the nonmercurated S86C/A89V CA mutant has a DNA distortion
      activity identical to that of mercurated wild-type MerR. A unique disulfide bond
      bridging this CA mutant's dimer interface was found and is proposed to constrain
      protein conformation in a manner analogous to mercuric ion binding in the wild
      type protein.

PMID- 8155635
TI  - Gene expression within a chromatin domain: the role of core histone
      hyperacetylation.
AB  - Scaffold-attached regions (SAR elements) increase transcriptional rates for
      integrated but not episomal templates, and this effect can be potentiated by
      using an epigenetically active reagent, butyrate. The action of butyrate is a
      direct one, not involving de novo protein synthesis, and can be mimicked by using
      a novel and highly specific inhibitor of histone deacetylases, (R)-trichostatin
      A. This leads to a model in which SAR elements serve to stabilize the chromosomal
      topology arising as a consequence of hyperacetylation of histone cores. The
      synergistic effects of histone hyperacetylation and SARs are mediated by promoter
      upstream elements since, for a simple TATA box, the response to both parameters
      is an additive one.

PMID- 8155636
TI  - Enhanced in vitro refolding of insulin-like growth factor I using a solubilizing
      fusion partner.
AB  - We have previously shown that human insulin-like growth factor I (IGF-I), fused
      to ZZ (two domains derived from staphylococcal protein A), can be refolded at
      relatively high concentrations, without the use of solubilizing agents
      [Samuelsson, E., Wadensten, H., Hartmanis, M., Moks, T., & Uhlen, M. (1991)
      Bio/Technology 9, 363-366]. Here we have studied this phenomenon in detail by
      characterizing the in vitro refolding of IGF-I, fused to one or two solubilizing
      Z domains and without a solubilizing fusion partner. The characterization
      included solubility studies of the reduced proteins and an evaluation of the
      aggregation occurring during the refolding process. The results suggest that the
      applied fusion protein strategy can be used to obtain a cis-acting chaperone-like
      effect during refolding in vitro. Fusion to one or two Z domains resulted in more
      than a 100-fold increase in the solubility of reduced IGF-I. In addition, the Z
      or ZZ fusion partners decrease multimerization of the IGF-I moieties during the
      renaturation. The fusion protein strategy may be an option to overcome the
      obstacles of insolubility and aggregation, frequently encountered when designing
      in vitro refolding processes.

PMID- 8155637
TI  - Analysis of amino acid residues in the H5-H6 transmembrane and extracellular
      domains of Na,K-ATPase alpha subunit identifies threonine 797 as a determinant of
      ouabain sensitivity.
AB  - Several amino acid residues of the alpha subunit of the Na,K-ATPase have been
      identified which alter ouabain sensitivity. These residues are located in the N
      terminal half of the alpha 1 subunit suggesting that this portion of the molecule
      may represent the binding site for cardiac glycosides. However, not all
      extracellular and transmembrane regions have been investigated, including the H5
      H6 membrane-spanning region. To determine if this region of the alpha subunit
      contributes to ouabain sensitivity, amino acids which have the potential to form
      hydrogen bonds were substituted with alanine, a non-hydrogen-bonding amino acid.
      cDNAs encoding enzyme containing these individual amino acid replacements were
      expressed in ouabain-sensitive HeLa cells, and the ability of the altered enzymes
      to confer ouabain resistance was examined. Nineteen amino acid substitutions were
      investigated. T797A (Thr 797 to Ala) was the only substitution which conferred
      ouabain resistance to sensitive HeLa cells. Three additional substitutions at
      this position (T797V, T797S, and T797D) were generated in order to examine the
      effects of the replacements of Thr 797 on ouabain inhibition of Na,K-ATPase
      activity. The T797V substitution conferred ouabain resistance, but T797S and
      T797D substitutions did not. The ouabain-resistant cell lines expressing the
      T797A and T797V substitutions exhibited Na,K-ATPase activity that was 60 and 70
      times more resistant to ouabain than the endogenous HeLa or sheep enzymes. The
      absence of a hydroxyl group at amino acid 797 may be responsible for the reduced
      sensitivity of the enzyme with substitutions at this position.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8155638
TI  - Kinetic analysis of lignin peroxidase: explanation for the mediation phenomenon
      by veratryl alcohol.
AB  - We investigated the role of veratryl alcohol in lignin peroxidase-catalyzed
      oxidation of anisyl alcohol with pre-steady-state and steady-state kinetic
      methods. Veratryl alcohol has been proposed to act as a redox mediator for
      substrates that are not directly oxidized by the enzyme. Alternatively, its
      mediation activity has also been attributed to its ability to protect the enzyme
      from H2O2-dependent inactivation. As previously reported, veratryl alcohol was
      able to stimulate the oxidation of anisyl alcohol. However, this stimulation is
      not due to mediation or protection of the enzyme. The stimulation can be
      attributed to the relative reactivity of anisyl alcohol with compounds I and II
      of lignin peroxidase. We found that anisyl alcohol reacts with compound I, but
      not with compound II. Therefore, inclusion of veratryl alcohol or another
      substrate, which reacts with compound II, is essential for completion of the
      catalytic cycle.

PMID- 8155639
TI  - Protein folding activities of Escherichia coli protein disulfide isomerase.
AB  - DsbA is an Escherichia coli periplasmic protein that mediates disulfide bond
      formation in newly secreted proteins in vivo. Addition of thiol reagents to
      purified dsbA reduces its disulfide bond and yields disulfide isomerase activity
      after removal of the thiol reagent. DsbA can catalyze the conversion of a stable
      misfolded protein, misfolded IGF-I (mis-IGF-I), to its correctly folded
      conformation under physiological conditions. This conversion is the result of
      breaking and re-forming two disulfide bonds. The uncatalyzed rate of this
      reaction is undetectable. Kinetic analysis of the reaction yielded a Km of 43
      microM and a kcat of 0.2 min-1. The oxidized form of dsbA stimulates the
      oxidative folding of completely reduced IGF-I at pH 7.0. Thus, dsbA has two
      possible functions depending on its redox state. The reduced form of the protein
      is a disulfide isomerase while the oxidized protein can assist formation of
      disulfide bonds in reduced substrates under physiological conditions.

PMID- 8155640
TI  - Equilibrium folding studies of tetrameric R67 dihydrofolate reductase.
AB  - R67 dihydrofolate reductase (DHFR) is an R-plasmid encoded enzyme that confers
      resistance to the antibacterial drug trimethoprim. This enzyme is not homologous
      in sequence or structure to chromosomal DHFRs. Equilibrium folding of tetrameric
      R67 DHFR was studied and found to be fully reversible. Formation of an inactive
      intermediate was assayed by loss of enzyme activity. Denaturation of the
      intermediate was monitored by concurrent changes in fluorescence and circular
      dichroism signals. Both transitions are protein concentration dependent. A simple
      model fitting these data is tetramer<==>2 dimers<==>4 unfolded monomers. No
      evidence for folded monomer was found. Global fitting of all the folding data
      yielded a delta GH2O of -9.63 kcal/mol for the initial transition and a delta
      GH2O of -12.35 kcal/mol for the second transition. In addition, thermal unfolding
      of tetrameric R67 DHFR was found to be reversible A folding intermediate also
      occurred during thermal unfolding as evidenced by the asymmetric endotherms and a
      delta Hcalorimetric/delta H(van't Hoff) ratio of 2.1.

PMID- 8155641
TI  - Phenol kinase activity of the serine/threonine-specific cAMP-dependent protein
      kinase: steric and electronic effects.
AB  - We have found that the cAMP-dependent protein kinase catalyzes the
      phosphorylation of a wide variety of peptide-based aromatic alcohols, thereby
      greatly amplifying the range of compounds recognized as substrates by this
      enzyme. This newly discovered enzyme-catalyzed reaction is sensitive to both
      steric and electronic effects. Substituents on the aromatic ring that are
      positioned para to the hydroxyl moiety lower the observed Km, presumably via a
      favorable interaction with an adjacent hydrophobic pocket. In contrast, electron
      withdrawing substituents have a slight adverse effect on the kinetics of
      phosphoryl transfer, an observation which is consistent with the notion that the
      rate of substrate turnover is dependent upon the nucleophilicity of the
      phosphorylatable hydroxyl moiety. As a corollary, electron-donating groups on the
      aromatic nucleus promote the rate of phosphoryl transfer to such an extent that
      the observed Vmax values approach those exhibited by aliphatic alcohols. This
      suggests that analogously appended electron-donating groups on tyrosine moieties
      could dramatically improve the modest Vmax values that are typical for tyrosine
      kinase-catalyzed reactions.

PMID- 8155642
TI  - Role of the S' subsites in serine protease catalysis. Active-site mapping of rat
      chymotrypsin, rat trypsin, alpha-lytic protease, and cercarial protease from
      Schistosoma mansoni.
AB  - The S' subsite specificity of four homologous serine proteases, rat chymotrypsin,
      rat trypsin, alpha-lytic protease, and cercarial protease from Schistosoma
      mansoni, was studied by measuring acyl-transfer reactions to 100 pentapeptide
      nucleophiles. Peptides of the general structures H-Xaa-Ala-Ala-Ala-Ala-NH2, H-Ala
      Xaa-Ala-Ala-Ala-NH2, and H-Ala-Ala-Xaa-Ala-Ala-NH2 were synthesized, where Xaa is
      D-Ala, Cit, and all natural amino acids except Cys. The variable residues of
      these nucleophiles occupy the P'1, P'2, and P'3 positions in acyl-transfer
      reactions. The P'1 and P'2 residues were found to influence the efficiency of the
      nucleophiles by more than 2 orders of magnitude, whereas the S'3 subsite shows a
      lower specificity in all four enzymes. We synthesized consensus peptides of the
      general structure H-aa1-aa2-aa3-Ala-Ala-NH2, in which two or three positions were
      occupied by amino acids that showed the highest specificity in the first series
      of nucleophiles. Peptides with optimal amino acid residues in the P'2 and P'3
      positions show a very high efficiency in chymotrypsin- and trypsin-catalyzed
      reactions. Otherwise, large specific side chains in the P'1 and P'3 positions of
      the nucleophiles show less than additive binding contributions due to steric
      hindrance. Comparison of chymotrypsin-catalyzed acyl-transfer reactions to
      nucleophiles of the structures H-Xaa-Leu-Arg-Ala-Ala-NH2 and H-Xaa-Ala-Ala-Ala
      Ala-NH2 reveals a significantly different P'1 specificity for both series which
      confirms steric hindrance between large P'1 and P'3 residues.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8155643
TI  - Identification of the catalytic base in long chain acyl-CoA dehydrogenase.
AB  - We have used molecular modeling and site-directed mutagenesis to identify the
      catalytic residues of human long chain acyl-CoA dehydrogenase. Among the acyl-CoA
      dehydrogenases, a family of flavoenzymes involved in beta-oxidation of fatty
      acids, only the three-dimensional structure of the medium chain fatty acid
      specific enzyme from pig liver has been determined (Kim, J.-J.P., Wang, M., &
      Paschke, R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7523-7527). Despite the
      overall sequence homology, the catalytic residue (E376) of medium chain acyl-CoA
      dehydrogenase is not conserved in isovaleryl- and long chain acyl-CoA
      dehydrogenases. A molecular model of human long chain acyl-CoA dehydrogenase was
      derived using atomic coordinates determined by X-ray diffraction studies of the
      pig medium chain specific enzyme, interactive graphics, and molecular mechanics
      calculations. The model suggests that E261 functions as the catalytic base in the
      long-chain dehydrogenase. An altered dehydrogenase in which E261 was replaced by
      a glutamine was constructed, expressed, purified, and characterized. The mutant
      enzyme exhibited less than 0.02% of the wild-type activity. These data strongly
      suggest that E261 is the base that abstracts the alpha-proton of the acyl-CoA
      substrate in the catalytic pathway of this dehydrogenase.

PMID- 8155644
TI  - Identification of the histidine ligands to the binuclear metal center of
      phosphotriesterase by site-directed mutagenesis.
AB  - In order to identify which of the seven histidines in phosphotriesterase
      participate at the active site/binuclear metal center of the enzyme, site
      directed mutagenesis has been employed to change, individually, each of the seven
      histidine residues to asparagine. In addition, the gene for the wild-type enzyme
      has been subcloned without its leader sequence behind a modified ribosomal
      binding site, leading to a 5-fold increase in protein expression. The seven
      mutants, H55N, H57N, H123N, H201N, H230N, H254N, and H257N, exhibit varying
      degrees of activity compared to the wild-type enzyme. The H123N and H257N mutants
      are as active as the wild-type enzyme, but all of the other mutant enzymes have
      10% or less activity. The metal content of the cobalt-purified mutant enzymes has
      been determined to be less than that of the wild-type enzyme in all cases. Each
      of the mutant enzymes has been converted to apoenzyme and reconstituted with 2
      equiv of zinc(II), cadmium(II), or cobalt(II). The kinetic parameters, Vmax and
      V/Km, and apparent pKa's have been determined for each of the reconstituted
      enzyme derivatives. In almost all cases, the apparent pKa's have shifted toward
      higher values. The pH-rate profiles for some of the reconstituted mutant enzymes
      are significantly different from those for the wild-type enzyme, indicating that
      other groups may become involved in the reaction mechanism upon mutation of the
      histidine residue to asparagine. His-123 is the only histidine residue that
      appears to have no involvement in the catalytic activity of
      phosphotriesterase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155645
TI  - Purification and characterization of N-acetylglucosamine-6-sulfate sulfatase from
      bovine kidney: evidence for the presence of a novel endosulfatase activity.
AB  - N-Acetylglucosamine-6-sulfate sulfatase (NG6SS) is an enzyme that catalyzes the
      hydrolysis of sulfate esters from the C-6 hydroxyl of N-acetylglucosamine. We
      report our purification and characterization of the enzyme and the discovery that
      it can remove sulfate from internally sulfated GlcNAc on glycopeptides and
      glycoproteins. The enzyme was purified from bovine kidney over 200,000-fold using
      a combination of ion-exchange and size-exclusion chromatography. NG6SS is soluble
      and occurs as a single subunit with apparent solution molecular weight of 60.2
      kDa on gel filtration chromatography and approximately 52.5 and 57.8 kDa on
      reducing and nonreducing SDS/PAGE, respectively. The enzyme is highly basic and
      exhibits a broad pH range with an optimum at pH 6.5 and a temperature optimum of
      37 degrees C. Among the mono- and disaccharide sulfates tested, only GlcNAc-6-SO4
      is an effective substrate with a Km of 4.7 mM, and either free sulfate or
      phosphate inhibits the activity. Unexpectedly, we found that the enzyme displays
      endosulfatase activity and quantitatively releases 35SO4 from 35SO4-labeled
      glycopeptides and intact glycoproteins isolated from human Molt-3 cells, which we
      have previously shown to synthesize glycoproteins containing GlcNAc-6-SO4
      residues within the sequence Gal beta 1-4[SO-3-6]-GlcNAc beta 1-R of complex-type
      N-linked oligosaccharides. The N-terminal sequence of the bovine NG6SS was
      homologous to a human-liver-derived N-acetylglucosamine-6-sulfatase. The
      endosulfatase activity of bovine kidney NG6SS may be important in its potential
      role in the degradation of sulfated glycans and may make this enzyme a valuable
      reagent to study the biological functions of sulfated glycoproteins.

PMID- 8155646
TI  - Selective activation of inhibitory G-protein alpha-subunits by partial agonists
      of the human 5-HT1A receptor.
AB  - Plasma membranes from Chinese hamster ovary (CHO) cells transfected with the
      serotonin 5-HT1A receptor have been incubated with full or partial receptor
      agonists and the photoreactive GTP analog, 4-azidoanilido-[alpha-32P]-GTP ([32P]
      AA-GTP), to characterize the resulting receptor-G-protein interactions.
      Subsequent solubilization and immunoprecipitation of the membranes with anti
      G(i)alpha-2 or anti-G(i)alpha-3 immunoglobulins revealed that full and partial
      agonists produce concentration-dependent labeling of the respective G-proteins
      with [32P]-AA-GTP. Full agonists of the 5-HT1A receptor [serotonin 5
      hydroxytryptamine (5-HT) and 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT)]
      produced a 7-12-fold increase in the labeling of G(i)alpha-2 and G(i)alpha-3,
      whereas partial agonists (rauwolscine and ipsapirone) produced a smaller
      incorporation (2-5-fold) of [32P]-AA-GTP by the same G-proteins. The
      concentration of agonist producing half-maximal binding of [32P]-AA-GTP by
      G(i)alpha-3 [5-HT, 48 +/- 1 nM; 8-OH-DPAT, 28 +/- 1 nM; ipsapirone, 22 +/- 6 nM]
      compared to G(i)alpha-2 [5-HT, 124 +/- 38 nM; 8-OH-DPAT, 40 +/- 1 nM, ipsapirone,
      82 +/- 7 nM] was lower with all agonists except rauwolscine, where the EC50's
      were similar (G(i)alpha-2, 604 +/- 145 nM; Gi alpha-3, 708 +/- 130 nM).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155647
TI  - 1,25-dihydroxyvitamin D3 modulates phosphorylation of serine 205 in the human
      vitamin D receptor: site-directed mutagenesis of this residue promotes
      alternative phosphorylation.
AB  - The vitamin D receptor (VDR) from a variety of animal species is a hormone
      modulated substrate for phosphorylation in vivo. In this report, we utilize an
      expression vector to produce recombinant human VDR (hVDR) in 1,25
      dihydroxyvitamin D3-treated COS-1 cells. Immunoprecipitation of the
      phosphorylated hVDR followed by gel purification and phosphoamino acid analysis
      revealed modification exclusively on one or more serine residues, consistent with
      previous studies of the VDR in other species. To identify the region of
      phosphorylation, immunoprecipitated and gel-purified hVDR from COS-1 cells was
      first mixed with purified hVDR isolated to homogeneity from Saccharomyces
      cerevisiae and then digested with trypsin or V8 protease, and the peptides were
      resolved on HPLC. The single phosphate-containing peptides were recovered and
      subjected to amino acid sequence analysis, revealing the modification to reside
      in a region extending from residue 171 to residue 206 common to both the tryptic-
      and the V8 protease-derived peptides. Sequential cleavage of similar VDR mixtures
      using trypsin and then CNBr, alpha-chymotrypsin, or thermolysin demonstrated an
      amino-terminal boundary of the phosphorylated peptide at 202. Selective manual
      Edman degradation of phosphorylated peptides beginning at 171, 195, and 200
      revealed phosphate release only at serine 205. This peptide contained an average
      of 8-fold less radioactive phosphate in the absence of prior treatment of the
      culture cells with 1,25(OH)2D3. Site-directed modification of VDR serine 205 to
      alanine, aspartate, or glutamate each led to fully functional proteins when
      assessed in a transactivation assay using several VDRE-linked natural promoters.
      Unexpectedly, evaluation of the serine 205 to alanine hVDR mutant revealed that
      this protein continued to be phosphorylated in a hormone-dependent manner on an
      alternative site. These studies show directly that hVDR serine residue 205, a
      consensus site for casein kinase II, is modified in vivo in response to hormone.

PMID- 8155648
TI  - Activation energy for permeation of phosphonium cations through phospholipid
      bilayer membrane.
AB  - The conductance caused by translocation of various phosphonium cations across
      phospholipid (from soybean) bilayer membrane was measured. Phosphonium cations
      used were tetraphenylphosphonium (TPP+) and triphenylalkylphosphonium cations
      formulated as (Phe)3-P(+)-(CH2)nCH3 (n = 0-5). The conductance was dependent on
      voltage applied externally to the membrane in accordance with a theory developed
      by previous authors. Using the theory, values of beta K(i) were determined, where
      beta and k(i) are a linear partition coefficient and a rate constant of
      transmembrane ion transport, respectively. Since beta k(i) depended on the
      phosphonium ion concentration, values extrapolated to infinite dilution, (beta
      k(i))0, were determined. Temperature dependence of (beta k(i))0 allowed us to
      estimate the activation energy of transport, Ea. For TPP+ thermodynamic values
      obtained were consistent with values calculated by Flewelling and Hubbell [(1986)
      Biophys. J. 49, 541-552]. When (Phe)3-P(+)-(CH2)nCH3 (n = 0-5) were used, E(a)
      depended on the odd or even of n. This "odd and even" pattern was observed in a
      variety of phenomena such as solubility in water, equivalent ionic conductivity
      in water, and 31P NMR chemical shift.

PMID- 8155649
TI  - Analysis of the binding of 3,3',5-triiodo-L-thyronine and its analogues to mutant
      human beta 1 thyroid hormone receptors: a model of the hormone binding site.
AB  - To understand the nature of the thyroid hormone binding site, we characterized
      the binding of 3,3',5-triiodo-L-thyronine (T3) and its analogues to eight
      naturally occurring mutated human beta 1 thyroid hormone receptors (h-TR beta 1).
      The mutant receptors were derived from patients with the syndrome of generalized
      thyroid hormone resistance, and each has a point mutation in the hormone binding
      domain (KT, R338W; TP, L450H; IR, D322H; NN, G347E; AH, P453H; OK, M442V; RL,
      F459C; and ED, A317T). Compared to the wild-type h-TR beta 1, binding of T3 was
      reduced by as much as 97% for the mutants. The order of binding affinity of wild
      type h-TR beta 1 to the analogues is T3 > D-T3 > L-thyroxine > 3,5-diiodo-L
      thyronine > 3,3',5'-triiodo-L-thyronine. The mutant receptors showed essentially
      the same order of reduced affinities for the analogues, but the amounts of the
      reductions varied in each case. These results suggest specific local interactions
      (interplay) of analogues with the mutated residues in the receptors. On the basis
      of these data and a putative structure of the hormone binding domains as an eight
      stranded alpha/beta barrel, we propose the location of the hormone in the binding
      site of h-TR beta 1. Ionic bonds anchor the hormone's alanine side chain to loop
      4 of the 8-fold alpha/beta barrel. The phenyl ring lies across the amino-terminal
      face of the domain with the phenoxy ring pointing downward into the barrel
      interacting with beta-strand 8 on the opposite side.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8155650
TI  - Membrane-binding amphipathic alpha-helical peptide derived from
      CTP:phosphocholine cytidylyltransferase.
AB  - A peptide corresponding to a portion of the amphipathic alpha-helical region of
      CTP:phosphocholine cytidylyltransferase was synthesized. This region of the
      enzyme was proposed to be the membrane-binding domain [Kalmar, G.B., Kay, R.J.,
      Lachance, A., Aebersold, R., & Cornell, R.B. (1990) Proc. Natl. Acad. Sci. U.S.A.
      87, 6029]. We have shown that the peptide is physically associated with PG
      vesicles. CD of the peptide in buffer suggested a primarily random structure,
      while, in the presence of trifluoroethanol, the peptide was alpha-helical.
      Anionic lipid vesicles promoted an alpha-helical conformation, whereas neutral or
      cationic lipid vesicles did not alter the random structure of the peptide,
      suggesting a selective stabilization of the alpha-helix by anionic membranes. The
      fluorescence of the single tryptophan residue, which lies on the hydrophobic face
      of the amphipathic alpha-helix, was studied. Anionic lipid vesicles specifically
      induced a shift in the fluorescence to a lower wavelength. Fluorescence quenching
      by the aqueous-phase quencher, I-, and the lipid-phase quencher 9,10-dibromo-PC
      was used to determine the accessibility of the tryptophan to each of these
      environments. The presence of anionic lipid vesicles, but not nonanionic lipid
      vesicles, decreased the quenching by I- suggesting that, in the presence of
      anionic lipids, the tryptophan residue is poorly accessible to the aqueous I-.
      Dibromo-PC significantly quenched the fluorescence only when present in anionic
      vesicles, confirming the membrane location of the tryptophan residue and the
      lipid specificity of this interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155651
TI  - Casein kinase 2 down-regulation and activation by polybasic peptides are mediated
      by acidic residues in the 55-64 region of the beta-subunit. A study with
      calmodulin as phosphorylatable substrate.
AB  - The noncatalytic beta-subunit is responsible for the latency of casein kinase 2
      (CK2) activity toward calmodulin. Twenty-one mutants of the beta-subunit bearing
      either deletions or Ala substitutions for charged residues in the 5-6, 55-70, and
      171-178 sequences have been assayed for their ability to substitute for wild-type
      beta-subunit as a suppressor of activity toward calmodulin. The only mutations
      that reduced the ability of the beta-subunit to suppress calmodulin
      phosphorylation activity, though being compatible with normal reconstitution of
      CK2 holoenzyme, were those affecting Asp55, Glu57 and the whole triplet Glu59-Asp
      Glu61. The activity of CK2 holoenzyme, either native or reconstituted, toward
      calmodulin can be elicited by a variety of polybasic effectors, including
      polylysine, polyarginine, salmine, and histones H4, H3, and, to a lesser extent,
      H2a and H2b. Histone H1 and polyamines are conversely ineffective. The latent
      "calmodulin kinase" activity of CK2 can also be specifically unmasked by a
      peptide (alpha[66-86]) reproducing a basic insert of the catalytic subunit. This
      effect is reversed by equimolar addition of a peptide (beta[55-71]) including the
      55-64 acidic stretch of the beta-subunit. Comparable polylysine stimulation was
      observed with the holoenzymes reconstituted with either beta wt or the beta
      mutants capable of assembling with the alpha-subunit, with the notable exception
      of those bearing Ala substitutions for acidic residues at positions 55, 57, and
      59-61. These were nearly insensitive to 42 nM polylysine, which conversely
      promotes a more than 10-fold increase of calmodulin phosphorylation with wild
      type beta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155652
TI  - Dynamic regulation of intact and C-terminal truncated insulin receptor
      phosphorylation in permeabilized cells.
AB  - Using digitonin-permeabilized Chinese hamster ovary (CHO) cells that were
      transfected with intact human insulin receptors (CHO/HIRc cells), we examined
      insulin receptor phosphorylation and dephosphorylation using pulse-chase
      techniques. Insulin activated receptor autophosphorylation on tyrosyl residues to
      a level severalfold over basal, reaching maximal levels after 2, 5, and 10 min of
      stimulation at 34, 18, and 6 degrees C, respectively. Phosphopeptide analysis
      revealed that the triply phosphorylated form of the 1146-kinase domain of the
      insulin receptor was the major species, which is characteristic of the fully
      active tyrosine kinase function. The dephosphorylation reaction was time- and
      temperature-dependent with t1/2 values of 0.67 and 2 min at 18 and 6 degrees C,
      respectively. Vanadate completely inhibited dephosphorylation. Under similar
      permeabilization conditions when compared with CHO/HIRc cells, CHO/delta CT cells
      (CHO cells overexpressing a mutated form of the receptor with a 43 amino acid
      deletion at the C-terminus) stimulated with insulin exhibited larger increases in
      receptor autophosphorylation levels and in tyrosine kinase activity toward a
      synthetic peptide substrate; the rate of CHO/delta CT receptor dephosphorylation
      was not reduced. There was near-complete absence of insulin receptor substrate 1
      (IRS-1) in the cell ghosts after permeabilization. We therefore examined the
      pattern of tyrosine phosphorylation and dephosphorylation of residual cellular
      proteins in permeabilized CHO/HIRc cells by Western blot analysis. In addition to
      the 95-kDa receptor beta-subunit, we detected the phosphorylation of two
      glycoproteins which included the commonly found 120-kDa protein and a novel 195
      kDa protein whose dephosphorylation rate is slower than that of receptor beta
      subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155653
TI  - Incorporation of norleucine at methionine positions in recombinant human
      macrophage colony stimulating factor (M-CSF, 4-153) expressed in Escherichia
      coli: structural analysis.
AB  - Expression of the 17.5-kDa truncated form of human recombinant macrophage colony
      stimulating factor (rM-CSF, 4-153) in Escherichia coli is complicated by the
      replacement of methionine residues by norleucine. In order to detect and
      quantitate this mistranslational event, the intact and the S
      carboxyamidomethylated proteins were analyzed by amino acid analysis, automated
      Edman amino acid sequencing, and electrospray mass spectrometry. In addition, the
      endoproteinase Glu-C generated peptides were subjected to amino acid sequencing,
      high-performance liquid chromatography, and electrospray ionization mass
      spectrometry. The extent of norleucine substitution in different batches of rM
      CSF varied between 0% and 20%. The relative instability of methionine residues
      needs to be considered when calculating the extent of norleucine substitution at
      methionine positions. The mass spectrometry of the intact rM-CSF allowed for
      examination of the distribution of multiply substituted methionine to norleucine
      species, and it enabled detection and quantitation of the norleucine
      incorporation down to the approximately 3% level. Selective ion chromatograms of
      molecular ions of interest obtained in reversed-phase high-performance liquid
      chromatography/electrospray ionization mass spectrometry of proteolytic fragments
      offered a reliable and fast method of detection and quantitation of norleucine
      containing peptides. Norleucine residues were uniformly distributed among all
      four methionine positions (10, 27, 61, and 65). A substitution of methionine by
      its structural norleucine analog does not have any effect on the activity of the
      refolded rM-CSF dimers.

PMID- 8155654
TI  - Chloride acts as a novel negative heterotropic effector of hemoglobin Rothschild
      (beta 37 Trp-->Arg) in solution.
AB  - The effects of chloride ion concentration on the rate constants for association
      of carbon monoxide with human hemoglobin A and a synthetic form of the mutant
      hemoglobin Rothschild (beta 37 Trp-->Arg) have been investigated by stopped-flow
      techniques. Previous studies of the structure [Kavanaugh et al. (1992)
      Biochemistry 31, 4111] and functional properties [Rivetti et al. (1993)
      Biochemistry 32, 2888] of hemoglobin Rothschild crystallized in the T state have
      demonstrated that the mutant arginine residues create new chloride ion binding
      sites and that chloride ions act to lower the oxygen affinity of hemoglobin
      Rothschild in these crystals. The studies reported here demonstrate a parallel
      effect of chloride ions on the rate of CO association with deoxygenated
      hemoglobin Rothschild in solution. Although the kinetics of CO binding to this
      hemoglobin in solution exhibit a Bohr effect, the chloride effect is independent
      of pH. In addition, we find that other halide ions have similar effects on the
      rate constants for the association of CO with this hemoglobin variant.

PMID- 8155655
TI  - Transport rate limited catalysis on macroscopic surfaces: the activation of
      factor X in a continuous flow enzyme reactor.
AB  - Blood coagulation is initiated on cells which present a macroscopic surface to
      the flowing blood stream. We have used a continuous flow enzyme reactor to model
      this system and to investigate the effects of shear rate and mass transport on
      the activation of factor X by the complex of the transmembrane protein, tissue
      factor, and the serine protease, factor VIIa. This initial step of blood
      coagulation was found to be half-maximal at very low enzyme densities (0.03
      0.06%) on the wall of the capillaries. In agreement with hydrodynamic theory, the
      apparent Km in the flow reactor was correlated with the cube root of the wall
      shear rate. These data indicate that at high tissue factor densities (> 0.6%) the
      activation of 150 nM factor X is controlled by the flux of X toward the surface,
      which is controlled by wall shear rate and substrate concentration. The
      appearance of the product, Xa, in the effluent was delayed to 8-12 min, which was
      caused by high-affinity binding of Xa to the phospholipid. This delay was
      considerably shortened by embedding tissue factor into PC or by coating the PS/PC
      surface with the phospholipid binding protein, annexin V. At low tissue factor
      densities, annexin V inhibited X activation by 45%, while no inhibition was
      observed at high densities. We demonstrate that when the reaction is limited by
      substrate flux, addition of further enzyme does not increase reaction rates. This
      contrasts with classical three-dimensional catalysis in which the initial
      velocity is ordinarily linear with the enzyme concentration.

PMID- 8155656
TI  - Evidence for the interaction of valine-10 in cystatin C with the S2 subsite of
      cathepsin B.
AB  - The interactions between wild-type or mutant recombinant forms of human cystatin
      C and rat cathepsin B were characterized by measuring progress curves for
      substrate hydrolysis in the presence of inhibitor. The investigation was guided
      by the use of computer modeling and explores the possibility that amino acid
      residues in the N-terminal region of cystatin C interact with substrate-binding
      regions in the target enzyme. With cystatin C that has Val-10 replaced by an Arg
      residue (Val10Arg cystatin C), the inhibition constant, K(i), increased 31-fold
      if the isosteric substitution Glu-245 to Gln was made in cathepsin B. When the
      wild-type form of the inhibitor was used, the corresponding effect on K(i) was
      less than 2-fold. In a similar study, using cathepsin B in which the substitution
      to Gln is instead at Glu-171, no such difference in how K(i) is affected was
      observed. Both Glu-245 and Glu-171 are located in the S2 subsite of cathepsin B.
      The observed effects on K(i) indicate that the additional positive charge
      introduced in Val10Arg cystatin C is interacting with the negative charge on Glu
      245 in cathepsin B when these two proteins form a complex; the cystatin variant
      is thus binding in a substratelike manner with this region of the enzyme.
      Indirectly, these results suggest that when native cystatin C and cathepsin B
      form a complex, Val-10 in the inhibitor interacts with the S2 subsite of the
      enzyme. A K(i) value of 0.13 nM was obtained for the interaction of Val10Arg
      cystatin C with papain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155657
TI  - Comparison of cytochrome b-559 content in photosystem II complexes from spinach
      and Synechocystis species PCC 6803.
AB  - Cytochrome b-559 is an integral component of photosystem II complexes from both
      plants and cyanobacteria. However, the number of cytochrome b-559 associated with
      the photosystem II reaction center has been the subject of controversy. Some
      studies have concluded that there is one heme equivalent of cytochrome b-559 per
      reaction center, some studies have found two, and some studies have reported
      intermediate values. Most of the previous experiments have used only one method
      to quantitate the antenna size of the preparation. In this study, we compare the
      cytochrome b-559 content in a cyanobacterial and a plant photosystem II
      preparation. The plant preparation is derived from spinach, and previous work has
      shown that it has an antenna size of approximately 100 chlorophylls [MacDonald,
      G. M., & Barry, B. A. (1992) Biochemistry 31, 9848-9856]. The cyanobacterial
      preparation is from Synechocystis sp. PCC 6803, and previous work has shown that
      it has an antenna size of approximately 60 chlorophylls [Noren, G. H., Boerner,
      R. J., & Barry, B. A. (1991) Biochemistry 30, 3943-3950]. Both preparations are
      isolated through the use of ion-exchange chromatography, and both preparations
      are monodisperse in the same nonionic detergent. In our comparative study, we
      quantitate antenna size by three different methods. Our work shows that,
      depending on the method used to estimate antenna size, the oxygen-evolving
      spinach photosystem II preparation contains 0.82-1.0 cytochrome b-559 per
      reaction center, while the oxygen-evolving cyanobacterial preparation contains
      1.5-2.1 cytochrome b-559 per reaction center.

PMID- 8155659
TI  - Mechanism of the acyl-carbon cleavage and related reactions catalyzed by
      multifunctional P-450s: studies on cytochrome P-450(17)alpha.
AB  - It is now well-known that conventional cytochrome P-450s catalyze hydroxylation
      reactions using an iron mono-oxygen species, the structure of which, as inferred
      from chemical model studies, may be drrepresented by the following canonical
      forms: FeV==O<-->(.+)FeIV==O<-->FeIV--O(.). Certain multifunctional P-450s,
      notably those involved in steroid biosynthesis, catalyze, in addition to
      hydroxylation reactions, an acyl-carbon cleavage process in which the
      participation of an iron peroxide intermediate, FeIII--OOH, has been suggested.
      However the possibility still exists that the C--C bond cleavage may also occur
      using the FeV==O species. We have scrutinized the chemical consequences of
      involving either an FeV==O or an FeIII--OOH species for five different C--C bond
      cleavage reactions. With respect to the status as well as the origin of hydrogen
      and oxygen atoms, in four of the examples the mechanism involving the FeV==O
      species makes the same prediction as that using the iron peroxide intermediate,
      that is, the incorporation of an atom of oxygen from O2 into acyl part of the
      cleaved fragment. The fifth example, however, involving the formation, with pig
      testes microsomes, of 17 alpha-hydroxyandrogen (androst-5-ene-3 beta,17 alpha
      diol) from pregnenolone, presents an interesting contrast--in this case different
      outcomes are predicted by the two mechanisms. These possibilities have been
      experimentally evaluated using substrates stereo- and regiospecifically labeled
      with heavy isotopes and incubated with pig testes microsomes under either 16O2 or
      18O2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155658
TI  - Characterization of the chloroplast cytochrome b6f complex as a structural and
      functional dimer.
AB  - Size analysis of the cytochrome b6f complex by FPLC Superose-12 chromatography
      and Blue Native PAGE indicated a predominantly dimeric component with M(r) = (1.9
      2.5) x 10(5). The true dimer molecular weight including bound lipid, but not
      detergent, was estimated to be 2.3 x 10(5). Size and shape analysis by negative
      stain single-particle electron microscopy indicated that the preparation of
      dimeric complexes contains a major population that has a protein cross section
      40% larger than the monomer, binds more negative stain, and has a geometry with a
      distinct 2-fold axis of symmetry compared to the monomeric complex. The dimeric
      species is more stable at higher ionic strength with respect to conversion to the
      monomeric species. SDS-PAGE of monomer and dimer preparations indicated that both
      contain the four major polypeptides in approximately equal stoichiometry and also
      contain the petG M(r) 4000 subunit. One bound chlorophyll a per monomer, part of
      the bound lipid, is present in monomer and dimer. The in vitro electron-transport
      activity (decyl-PQH2-->PC-ferricyanide) of the separated dimer was comparable to
      that of the isolated b6f complex and was 4-5-fold greater than that of the
      monomer preparation, whose activity could be attributed to residual dimer. No
      difference in the properties of the dimer and monomer was detected by SDS-PAGE or
      redox difference spectrophotometry that could account for the difference in
      activities. However, the concentration of the Rieske [2Fe-2S] center was found by
      EPR analysis of the gy = 1.90 signal to be lower in the monomer fraction by a
      factor of 3.5 relative to the dimer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155660
TI  - Structural determinants of cytochrome P450 2B1 specificity: evidence for five
      substrate recognition sites.
AB  - Twelve site-directed mutants of rat cytochrome P450 2B1 distributed over seven
      positions and four putative substrate recognition sites (SRS) were constructed
      and expressed in COS cells. Function was examined using androstenedione and
      testosterone as substrates. Substitutions at positions 303, 360, and 473 did not
      markedly affect the regio- or stereoselectivity of androgen metabolism, whereas
      mutants in positions 206 (SRS-2), 302 (SRS-4), and 363 and 367 (SRS-5) exhibited
      markedly different steroid metabolite profiles compared with parental P450 2B1.
      In particular, the Phe-206-->Leu substitution conferred androgen 6 alpha- and
      testosterone 7 alpha-hydroxylase activities, and the Thr-302-->Ser substitution
      suppressed androgen 16 beta-hydroxylation in favor of androstenedione 16 alpha-
      and testosterone 15 alpha-hydroxylation. Replacement of Val-363 or Val-367 with
      Ala conferred androgen 15 alpha-hydroxylase and 6 beta-hydroxylase activities,
      respectively, and suppressed susceptibility to mechanism-based inactivation by
      the P450 2B1-selective chloramphenicol analog N-(2-p
      nitrophenethyl)chlorofluoroacetamide. The Val-367-->Ala mutant was also resistant
      to chloramphenicol itself. The Leu mutant at position 363 exhibited increased
      specificity for androstenedione and testosterone 16 beta-hydroxylation, whereas
      the Leu mutant at position 367 exhibited decreased stereospecificity. Most
      interestingly, the size of key residues identified plays a critical role in
      governing steroid hydroxylation from the alpha-face or beta-face and
      hydroxylation on the D-ring or the B-ring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155661
TI  - Models and molecular orbital semiempirical calculations in the study of the
      spectroscopic properties of bovine serum amine oxidase quinone cofactor.
AB  - The electronic properties of 2,4,5-trihydroxyphenylalanine quinone (TPQ), the
      cofactor of bovine serum amine oxidase [Janes, S. M., Mu, D., Wemmer, D., Smith,
      A. J., Kaur, S., Maltby, D., Burlingame, A. L., & Klinman, J. P. (1990) Science
      248, 981-987], and some adducts with hydrazines were investigated by means of low
      molecular-weight models and semiempirical molecular orbital calculation methods.
      The enzyme visible band was assigned to the first pi-->pi* transition of the
      cofactor in p-quinonic form, with the C-4 hydroxyl ionized and hydrogen bonded
      either to a water molecule or to a basic protein residue. The spectra of the
      protein adducts with some substituted hydrazines were well accounted for by
      assuming the inhibitor bound to the C-5 carbonyl, usually in azo form. The adduct
      with the unsubstituted hydrazine was instead assigned an o-quinone hydrazone
      form, stabilized by an internal hydrogen bond between the amino group and the
      ortho carbonyl oxygen, a larger electron delocalization, and formation of a
      hydrogen bond at the C-6 ionized hydroxyl. On the basis of these assignments, the
      reaction of the protein with benzylhydrazine [Morpurgo, L., Agostinelli, E.,
      Muccigrosso, J., Martini, F., Mondovi, B., & Avigliano, L. (1989) Biochem. J.
      260, 19-25] was rewritten. All examined electronic transitions, though highly
      sensitive to cofactor ionization and hydrogen bonding, could be accounted for
      without introducing perturbations due to copper. This confirms that copper is not
      within bonding distance of the oxidized cofactor.

PMID- 8155662
TI  - Oxidation-reduction potential dependence of photosystem II carbonic anhydrase in
      maize thylakoids.
AB  - In characterizing the carbonic anhydrase (CA) found in maize thylakoid membranes,
      it was observed that the enzyme's activity was inhibited somewhat when the Hill
      oxidant, ferricyanide, was given in the dark [Stemler, A. (1986) Biochim.
      Biophys. Acta 850, 97-107]. In the present work, a redox titration of this effect
      shows that the CA activity is mediated by a component that has a midpoint
      potential (Em) of about 485 mV at pH 6.5 and a pH dependence of 60 mV/pH. These
      redox titration characteristics are identical to those of the redox mediator
      "D480", which modulates formate and bicarbonate binding affinity to photosystem
      II (PS II). Bicarbonate binds to PS II more readily, and CA activity is higher,
      when D480 is reduced, whereas both bicarbonate binding and thylakoid-bound CA
      activity are low when D480 is oxidized in the dark by ferricyanide. Both the low
      bicarbonate binding affinity and the low CA activity induced by the presence of
      ferricyanide are reversed by a single saturating flash of light. In contrast, the
      activity of soluble CA, which is extracted from maize mesophyll cytosol, does not
      exhibit any redox dependence in the range 400-550 mV. Furthermore, thylakoid
      bound CA activity is inhibited by 5 mM ZnCl2 by as much as 75%, whereas the
      activity of soluble CA shows no significant decrease induced by ZnCl2. Also, at a
      medium potential of 400 mV, ferricyanide (1 mM) inhibits soluble CA activity by
      88% and thylakoid-bound CA activity by only 18%. It is concluded from these
      results that CA activity observed in thylakoids arises from CA inherent to PS II
      and is not some form of contamination by soluble CA. Possible roles of CA in PS
      II reaction mechanisms are discussed.

PMID- 8155663
TI  - Na,K-ATPase and carboxyfluorescein distinctly alter vesicle formation in vitro.
AB  - The mechanism of vesicle formation as well as the precise reasons for their
      stability are not known. Thus, it is necessary to simulate the process in vitro
      for studying its mechanism. If phospholipids are suspended in physiological
      solution by means of cholate and the detergent is then removed by dialysis, the
      phospholipids self-assemble to form unilamellar vesicles. We report here that the
      addition of Na,K-ATPase (an integral membrane protein) to the phospholipids
      changes the vesicle structure, they become larger and a multilamellar population
      appears. By contrast, carboxyfluorescein, a compound commonly used for labelling
      the aqueous vesicle compartment, produces an unexpected effect on vesicle
      structure by inducing complex, tore-like intravesicular multilayer formations
      associated with a 5-fold increase in diameter. Thus, the presence of a protein in
      the membrane phase or of a compound in the water phase can influence and direct
      vesicle formation in vitro; these model systems might give some clues to possible
      physicochemical or biological factors governing the formation of natural membrane
      structures.

PMID- 8155664
TI  - Reversal of doxorubicin resistance and catalytic neutralization of lysosomes by a
      lipophilic imidazole.
AB  - A number of lipophilic nitrogenous bases, designed to act as membrane-active,
      catalytic proton transfer agents, were tested for their ability to neutralize the
      acidity of lysosomes, a model for other acidic intracellular vesicles involved in
      drug sorting. The most successful of these, an imidazole 1, caused a 1.7 unit
      rise in lysosomal pH of RAW cells at 100 microM, compared to a 0.2 and 1.4 unit
      rise for ammonium chloride at 100 microM and 10 mM, respectively. Compound 1 also
      exhibited potent reversal of doxorubicin (DOX) resistance in the HCT116-VM46 cell
      line by a factor of 14 over the sensitive strain, and superior to that of widely
      used verapamil (VRP) by a factor of 1.75 at 20 microM. It also has antiviral
      properties, and potential applications in other lysosome-related areas such as
      immunotoxin potentiation and the control of bacterial toxins, immune response,
      prion replication, malaria and intralysosomal microorganisms.

PMID- 8155665
TI  - Co-solubilization of bradykinin B2 receptors and angiotensin-converting enzyme
      from guinea pig lung membranes.
AB  - Bradykinin B2 receptor-like binding activity was solubilized from guinea pig lung
      using the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulphonate (Chaps). The binding of [3H]bradykinin to the soluble fraction
      was time-dependent and saturable. Scatchard analysis of equilibrium binding data
      indicated that the soluble extract contained a single class of binding sites with
      a Kd of 696 pM and a Bmax of 57 fmol/mg protein. Unlabelled bradykinin and B2
      antagonists inhibited the binding of [3H]bradykinin to Chaps-solubilized extracts
      with relative potencies similar to those observed with the low-affinity membrane
      bound binding sites. Following partial purification of the soluble preparation,
      using anion exchange (DEAE-Sephacel) and gel filtration (Aca 34) column
      chromatography steps, two peaks eluted off the column were able to bind
      [3H]bradykinin and have molecular masses of 168 and 98.5 kDa. The former seems to
      represent binding of bradykinin to angiotensin converting enzyme (ACE, EC
      3.4.15.1) and the latter binding to bradykinin receptor. Using purified
      commercial ACE, we show that the binding of [3H]bradykinin to ACE can easily be
      distinguished from that of the bradykinin receptor, since both B1 and B2 ligands
      were able to inhibit bradykinin binding with affinities clearly different from
      that expected for a bradykinin receptor.

PMID- 8155666
TI  - The transition of alpha-helix to beta-structure of poly(L-lysine) induced by
      phosphatidic acid vesicles and its kinetics at alkaline pH.
AB  - Static and dynamic circular dichroism (CD) measurements were carried out for
      poly(L-lysine) in suspensions of dilauroylphosphatidic acid (DLPA) vesicles at
      alkaline pH (8-11.5). The static experiments demonstrated that the alpha-helix of
      poly(L-lysine) induced by deprotonation in alkaline solutions is transformed to
      beta-structure by the addition of DLPA vesicles. Stopped-flow CD measurements for
      such order-to-order transition revealed that the rate determining step is the
      unfolding process of alpha-helix to random coil. Previously, we have reported the
      conformational change of poly(L-lysine) induced by DLPA vesicles at neutral pH,
      where the beta-structure transition from random coil was observed. Thus two types
      of transition of poly(L-lysine) are observed depending on bulk pH, i.e., from
      random coil to beta-structure and from alpha-helix to beta-structure. So far the
      phospholipid-induced conformations of poly(L-lysine) were interpreted in terms of
      counterbalance between the positively charged terminals of the lysyl chains and
      the negative headgroups of the phospholipid in vesicle. However, present work
      indicates the direct interaction other than electrostatic interaction between the
      lysyl chain and phosphate groups of the lipid.

PMID- 8155667
TI  - Kinetics of subgel formation in DPPC: X-ray diffraction proves nucleation-growth
      hypothesis.
AB  - Wide-angle and low-angle X-ray diffraction data were obtained during the time
      course of the gel to subgel phase transformation in fully hydrated DPPC. When the
      system was kept close to equilibrium by following a T-jump protocol, the X-ray
      data unequivocally demonstrate the coexistence of growing subgel and shrinking
      gel domains. When the system was supercooled and held further from equilibrium as
      in previous studies, the kinetic behavior was more complicated. These data prove
      that the basic mechanism for the gel to subgel phase transformation is one of
      nucleation of subgel domains followed by growth of the domains.

PMID- 8155668
TI  - Sodium selenite as modulator of red cell shape.
AB  - Addition of sodium selenite to human red cells, under ATP deplete conditions,
      induces a rapid oxidation of both glutathione and protein sulphydryl groups.
      Selenite also inhibits the discocyte-echinocyte shape transformation and stops
      the process before completion. Parallel to the effect on shape, selenite reduces
      the dephosphorylation of phosphatidylinositol 4,5-bisphosphate and
      phosphatidylinositol 4-monophosphate. Therefore our results support a shape
      change mechanism based on the metabolism of phosphoinositides and compatible with
      the bilayer-couple hypothesis.

PMID- 8155669
TI  - Distribution of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in rat
      testis mitochondria.
AB  - The distribution of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in
      isolated rat testis mitochondria was investigated, using a reverse sucrose
      density gradient centrifugation procedure for the separation of the inner and
      outer membranes and the contact sites between the two membranes. The results
      indicate that PHGPx is largely localized in the contact sites fraction. This
      finding might therefore suggest that the enzyme has more than just an antioxidant
      function.

PMID- 8155670
TI  - Evidence that channels below 1 pS cause the volume-sensitive chloride conductance
      in T84 cells.
AB  - The volume-activated chloride current of T84 human colonic cells was studied
      using the whole-cell patch clamp. The current appeared reliably with a mild
      osmotic gradient and in the absence of intracellular ATP. It reversed at the
      chloride equilibrium potential and was blocked by the chloride channel blocker
      DIDS. Development of the current was accompanied by an increase in the current
      noise variance, typical of increasing ion channel open probability. Noise
      variance was always well-fitted by a double Lorentzian relationship with corner
      frequencies at approximately 1.7 Hz and approximately 60 Hz. The increase in
      variance during development of the volume-sensitive current was mostly due to an
      increase in the high frequency component. The relationship between noise variance
      and membrane current was well-fitted by a relationship with a single channel
      conductance of approximately 0.2 pS.

PMID- 8155671
TI  - Frequency dependence of electric-field-induced orientation of myelin tubes.
AB  - Orientation induced by an alternating electric field was studied for myelin tubes
      of egg phosphatidylcholine (egg-PC) in water and in KCl electrolyte solution. The
      orientation was also studied for myelin tubes of egg-PC/cholesterol mixtures in
      water. The orientation effect was measured by the bending curvature of myelin
      tubes with hairpin-like deformation at frequencies between 10 kHz and 20 MHz. The
      bending deformation of egg-PC myelin tubes in water decreased abruptly with a
      decreasing frequency within the low-frequency range below 100 kHz, and shrinkage
      of myelin tubes was often observed. The bending deformation decreased as the
      frequency was increased in a higher frequency range. The profile of the frequency
      dependence for egg-PC in KCl solution was similar to that in water but shifted
      towards a higher frequency. At low KCl concentrations below 3 mM, the relaxation
      frequency increased proportionally with increasing an KCl concentration, which
      was due to a proportional increase in the conductivity of the surrounding medium.
      Similar profiles of the frequency dependence were observed for egg-PC/cholesterol
      mixtures but with no shift in the relaxation frequency. These data in the high
      frequency range fitted well with calculations based on theoretical equations for
      the electric-field-induced orientation of nonspherical particles. The
      conductivity of myelin tubes was estimated to be in the order of 10(-4) S/m in
      water and of 10(-3) S/m at the low KCl concentrations. The bending modulus of a
      bilayer membrane was estimated to be (1.0 +/- 0.5) x 10(-19) J for egg-PC in
      water. No change in the bending modulus was observed for egg-PC in KCl solution.
      However, for egg-PC/cholesterol mixtures in water, the bending modulus abruptly
      increased to (1.8 +/- 0.5) x 10(-19) J at a cholesterol concentration of 40 mol%.

PMID- 8155672
TI  - Thermodynamics of transfer of indocarbocyanines from gel to fluid phases of
      phospholipid bilayers.
AB  - Application of the regular solution model to thermal transition data obtained by
      differential scanning calorimetry has allowed the determination of partition
      coefficients, Kp, and the thermodynamics of transfer of a series of
      indocarbocyanine solutes between the gel and fluid phases of phospholipid
      bilayers. The indocarbocyanines with alkyl chain lengths of 12 to 22 carbons were
      partitioned between dipalmitoyl- and distearoylphosphatidylcholine phases at the
      transition temperatures of the gel-liquid-crystal phase transition. The results
      indicate that as the alkyl chain length of the solute nears that of the acyl
      chains of the bilayer lipid, the free energy of transfer from gel to fluid is
      least negative, and the enthalpy of transfer is most positive. There is almost
      complete entropy-enthalpy compensation in the transfer process. Comparison of the
      partition coefficients with published values determined by a fluorescence method
      show good agreement when the differences in temperature of the measurements are
      accounted for.

PMID- 8155673
TI  - Solid-phase binding analysis of N-CAM interactions with brain fodrin.
AB  - The large cytoplasmic domain form of the neural cell adhesion molecule N-CAM has
      been reported to interact specifically with fodrin, a submembranous cytoskeletal
      protein. We tested the abilities of fodrins from bovine brain and embryonic
      chicken brain to bind to N-CAM that had been isolated from differentiated or
      undifferentiated mouse N2A neuroblastoma cells or from the brains of embryonic
      day 11 or day 14 chickens. Labeled fodrin samples bound with immobilized fodrin
      at a minimum soluble fodrin concentration of 2.5 x 10(-8) M, but the labeled
      fodrin did not bind to the immobilized N-CAM when incubated at 20-fold higher
      fodrin concentrations.

PMID- 8155674
TI  - Further characterization of the sodium-dependent nucleoside transporter (N3) in
      choroid plexus from rabbit.
AB  - The Na+/nucleoside cotransporter in rabbit choroid plexus differs from
      Na+/nucleoside cotransporters in other tissues in terms of substrate selectivity
      and stoichiometry. The overall goal of this study was to further characterize the
      kinetics of this system (N3). Choroid plexus tissue slices obtained from rabbit
      brain were depleted of ATP and treated with valinomycin and K+. Na+/thymidine
      uptake at 30 s in the presence of an inside negative potential difference was
      significantly greater than in the absence of a potential difference.
      Na+/thymidine uptake was not significantly affected by replacing chloride with
      either thiocyanate or sulfate. The Km of Na+/guanosine uptake was 149, 85.2 and
      30.5 microM in the presence of a 25, 50 and 100 mM Na+ gradient, respectively,
      whereas the Vmax was unaffected, suggesting that Na+ binds first to the
      cotransporter, then, the nucleoside. Therapeutically relevant base-modified
      nucleoside analogs, 5-fluorouridine, 2-chloroadenosine and 5-iododeoxyuridine,
      significantly inhibited Na+/thymidine uptake with IC50 values (mean +/- S.E.) of
      12.0 +/- 2.3, 21.3 +/- 2.2 and 24.4 +/- 2.1 microM, respectively, whereas
      nucleoside analogs structurally modified on the ribose ring, 3'-azidothymidine,
      dideoxyinosine and dideoxycytidine (100 microM) did not. These studies suggest
      that Na+/nucleoside cotransport in the choroid plexus is electrogenic and is not
      dependent on chloride. This cotransporter, which is present in choroid plexus but
      not in renal brush-border membrane vesicles from rabbit, may play a role in the
      disposition of clinically relevant base-modified nucleoside analogs into and out
      of the brain.

PMID- 8155675
TI  - Crypt cell production rate, enterocyte turnover time and appearance of transport
      along the jejunal villus of the rat.
AB  - Intestinal nutrient absorption is subject to adaptation with, for example,
      diabetes, diet lipid variations (isocaloric semisynthetic diets enriched with
      saturated (S) or polyunsaturated (P) fatty acids), ileal resection and abdominal
      irradiation. These models were used in rats to assess dynamic morphology and
      distribution of amino acid transporter along the villus. The enterocyte migration
      rate (EMR) was measured using [3H]thymidine; the vincristine metaphase arrest
      technique was used to determine the crypt cell production rate (CCPR);
      quantitative autoradiography was used to assess the time and age of enterocytes
      when the uptake of 1 and 20 mM [3H]leucine and [3H]lysine was initiated along the
      villus. The enhanced jejunal uptake of nutrients which occurs after a 50% distal
      enterectomy was associated with a fall in EMR and CCPR, yet the enhanced nutrient
      uptake which occurs in diabetes is not associated with any alteration in EMR,
      CCPR, enterocyte transport pool (ETP), i.e., the length of the enterocyte column
      along with the villus containing amino acid transporter) or expression of
      transporter along the villus. The reduced uptake of nutrients in rats fed P as
      compared with S was associated with increased rather than decreased ETP and age
      of the enterocytes at the tip of the villus. The reduced nutrient uptake which
      occurs 3 days after abdominal irradiation was associated with increased EMR and
      CCPR, and reduced ETP and age of enterocytes of the tip of the villus. However,
      14 days after irradiation when nutrient transport remains reduced, these
      parameters have returned to normal. Thus, alterations in nutrient transport may
      be associated with changes in the dynamic morphology of the intestine, but the
      two processes are not necessarily interdependent. We speculate that the changes
      in the dynamic morphology of the intestine, and the changes of amino acid
      transport which occurs in these models of intestinal adaptation, are
      independently controlled.

PMID- 8155676
TI  - The stretch-activated ion channel blocker gadolinium also blocks L-type calcium
      channels in isolated ventricular myocytes of the guinea-pig.
AB  - We show that gadolinium (Gd3+) is a potent calcium channel blocker in guinea-pig
      isolated ventricular myocytes. A dose-dependent inhibition of ICaL was found with
      an EC50 of 1.4 microM and a complete inhibition at 10 microM Gd3+. When compared
      with Cd2+, it appeared that the blockade of ICaL is a complex phenomenon probably
      involving more than one site of interaction (a Hill coefficient of 1.6 was found
      for Gd3+ vs. 1.0 for Cd2+). It is concluded that Gd3+ ions completely block ICaL
      at concentrations used to block stretch-activated channels (SAC), rendering its
      use as a specific SAC inhibitor problematic.

PMID- 8155677
TI  - Fluid flow increases membrane permeability to merocyanine 540 in human
      endothelial cells.
AB  - Fluid shear stress is a ubiquitous stimulus of mammalian cell metabolism;
      however, its signal transduction pathway is unknown. We hypothesized that shear
      stress may alter some physical properties of the cell membrane. Using primary
      human umbilical vein endothelial cells (HUVECs), we investigated the effects of
      shear on the cell membrane by monitoring flow-induced changes in the uptake of
      the amphipath merocyanine 540 (MC540). Under static conditions, MC540 was rapidly
      internalized by HUVECs at 37 degrees C, and so was the membrane impermeant dye
      lucifer yellow, suggesting that the MC540 uptake was partly due to endocytosis.
      However, exposure to steady flow for 5 min at 37 degrees C induced an increase in
      MC540 uptake while that of lucifer yellow was unchanged, suggesting that the flow
      induced increase in MC540 uptake was not endocytosis-related. The increase in
      MC540 uptake was significant for levels of steady shear of 6 dyne/cm2 and above.
      Pulsatile flow was more stimulatory than steady flow at 2 dyne/cm2, but no
      significant difference between the two was seen at higher shear stress levels. We
      conclude that fluid shear stress enhanced the uptake of MC540 by a mechanism
      other than endocytosis, suggesting an increase in plasma membrane permeability
      during exposure of the cells to shear stress.

PMID- 8155678
TI  - Ankyrin inhibits binding of erythrocyte spectrin to phospholipid vesicles.
AB  - The studies on binding of erythrocyte spectrin to frozen and thawed phospholipid
      liposomes and its inhibition by ankyrin were performed. It was found that ankyrin
      inhibited up to 60% binding of spectrin by
      phosphatidylethanolamine/phosphatidylcholine vesicles. It was able to dissociate
      up to 40% of spectrin from this complex. Ankyrin inhibition of binding of
      phosphatidylserine/phosphatidylcholine vesicles by spectrin, although much lower,
      was also observed.

PMID- 8155679
TI  - Developmental changes of renal brushborder membrane ionic permeability.
AB  - Renal brush-border membrane vesicles (BBMV) show an age-dependent increase in
      height of the Na(+)-gradient driven overshoot for glucose and proline uptake.
      Conversely, early uptake of 22Na+ is more rapid in BBMV from kidney of 7-day-old
      vs. adult rats. To understand the mechanisms responsible for these observations,
      ionic permeability characteristics of BBMV from different aged animals were
      determined using an electrical potential sensitive fluorescent dye, diS-C3(5).
      Absolute and relative ionic permeabilities were determined after a 3-h incubation
      in 100 mM KCl. Intravesicular K+ ([K+]in), a measure of absolute K+ permeability,
      was calculated from the extravesicular K+ at which valinomycin produced no
      potential difference (PD). [K+]in was significantly lower in vesicles from 7-day,
      compared to adult (P < 0.01). While Cl- permeability, relative to that of K+ was
      similar, PNa+/PK+ decreased significantly with age (P < 0.05, 7 day vs. adult).
      In the presence of an inwardly directed NaCl gradient, the lower PNa+ relative to
      PCl- of the adult vesicles would result in a less positive intravesicular charge,
      which would therefore augment Na(+)-solute co-transport. Fluorescence
      polarization studies also show that lipids from BBM vesicles of 7-day-old rats
      are more fluid than those from adult. These differences are likely due to
      developmental lipid compositional changes, which influence membrane transport and
      permeability characteristics. These findings would explain, in part, the age
      dependent alterations of renal BBMV solute transport.

PMID- 8155680
TI  - Hydration of DOPC bilayers by differential scanning calorimetry.
AB  - The phase diagram of the unsaturated lipid dioleoylphosphatidylcholine (DOPC) in
      aqueous multibilayer dispersions has been constructed from a series of
      differential scanning calorimetry (DSC) thermograms over the temperature range
      from -40 to +10 degrees C, covering a range of hydration levels from the
      monohydrate to excess free water. Both the lipid chain melting transition and the
      ice melting point are found to be hydration dependent. From their respective
      variations it is found that the bilayer in the gel phase binds approximately 9
      H2O per lipid, while the liquid-crystalline state has a saturation limit near 20
      H2O. The water transition exhibits a hydration-dependent melting point
      depression, which can be explained in terms of newly incorporated water between
      the bilayer surfaces upon melting of the acyl chains, and which is reminiscent of
      the events that occur at the pre-transition for saturated lipids. From the
      melting point depression, the thermodynamic activity of the interbilayer water
      can be calculated and thus the repulsive hydration force characterized
      quantitatively. We evaluate a (non-isothermal) hydration force decay constant
      around 2.8 H20, which demonstrates that this DSC approach is well-suited for
      quantitatively characterizing the hydration properties of unsaturated lipid
      dispersions at low temperature.

PMID- 8155681
TI  - Effect of arginine modification on K(+)-dependent leucine uptake in brush-border
      membrane vesicles from the midgut of Philosamia cynthia larvae.
AB  - The effect of phenylglyoxylation on the midgut K(+)-dependent leucine transport
      was studied using lepidopteran brush-border membrane vesicles. The inhibition of
      leucine uptake by phenylglyoxal (PGO) showed a biphasic inactivation pattern. The
      second-order rate constant for the slow and fast phases were 0.0020 mM-1 min-1
      and 0.0091 mM-1 min-1, respectively. However, substitution of borate buffer for
      Hepes-Tris buffer produced a mono-exponential inactivation pattern, suggesting
      modification of a single arginine group. The effect of PGO was dose-dependent and
      the concentration causing half-maximal inhibition of leucine uptake was 5.1 +/-
      0.3 mM. Leucine transport was significantly inhibited also in the absence of a
      potassium electrochemical gradient (i.e., [K+]in = [K+]out = 100 mM), suggesting
      that inhibition was not related to a decrease in the driving force. Moreover,
      intravesicular volume remained unchanged after preincubation with PGO. Kinetic
      analysis of the interaction of PGO with the leucine cotransporter revealed that
      (i) inhibition was related to a decrease in the Vmax value and (ii) neither
      leucine nor K+ were able to prevent the inhibition. Our results suggest an
      important role for arginine residues in the molecular mechanism of K+/leucine
      cotransport in lepidopteran larvae midgut.

PMID- 8155682
TI  - Immunoelectron microscopic analyses of Maillard reaction products in bovine
      anterior lens capsule and Descemet's membrane.
AB  - It has been hypothesized that Maillard reaction products form in basement
      membranes during aging and may affect protein turnover. The purpose of this study
      was to localize Maillard reaction products in intact lens capsules and Descemet's
      membranes by immunoelectron microscopy to determine whether Maillard products
      accumulated with age and whether basement membrane thickness increased to a
      similar degree. The monoclonal antibodies antiglucitollysine and antipyrraline
      were employed to detect the products in native and glucose-treated bovine
      basement membranes. The content of basic amino acids, furosine, and fluorophores
      (370/440), as well as resistance to trypsin digestion showed that the basement
      membranes formed significant quantities of Maillard products when incubated with
      200 mM glucose in vitro (P < 0.05). Likewise, incubation in 200 mM glucose
      resulted in at least a 4-fold increase in immunoreactivity (P < 0.001). Native
      basement membranes increased in thickness more than 2-fold with age (P < 0.001).
      Immunoreactivity varied similarly in that bound antiglucitollysine increased
      approx. 2-fold and antipyrraline approx. 3-fold in old vs. young basement
      membranes, but these differences were significant only in pyrraline
      immunoreactivity in the lens capsule (P < 0.01). Advanced products other than
      pyrraline may accumulate in Descemet's membrane since significant increases in
      fluorescence and resistance to trypsin were noted. These data suggest that the
      Maillard reaction may, to a small degree, contribute to basement membrane
      thickening.

PMID- 8155683
TI  - Liposome-complement interactions in rat serum: implications for liposome survival
      studies.
AB  - Serum complement opsonizes particles such as bacteria for clearance by the
      reticuloendothelial system. Complement has been reported to interact with
      liposomes and therefore may mediate the reticuloendothelial system clearance of
      liposomes. This study has used a rat serum model to define some of the
      characteristics of liposomes which modulate their ability to activate complement.
      Using functional hemolytic assays and C3/C3b crossed immunoelectrophoresis, we
      have demonstrated that liposomes activated rat complement in a dose-dependent
      manner with higher concentrations of liposomes activating higher levels of
      complement. The detection of complement activation required the inclusion of
      phospholipids bearing a net charge. Complement activation occurred via the
      classical pathway; no alternative pathway activation was detected. The presence
      of cholesterol contributed to complement activation in a dose-dependent manner.
      Phospholipid fatty acyl chain length did not influence complement activation
      while the introduction of unsaturated acyl chains markedly decreased levels of
      complement activation. Liposome size also influenced complement activation with
      400 nm unilamellar vesicles more effectively activating complement than 50 nm
      vesicles for equivalent amounts of exposed lipid. These studies demonstrate that
      the composition of the liposome greatly affects the in vitro activation of rat
      serum complement and suggest that the biological half-life of liposomes in the
      circulation of rats may be altered by changing the liposome composition to reduce
      complement activation.

PMID- 8155684
TI  - Synthesis of surface sphingomyelin in the plasma membrane recycling pathway of
      BHK cells.
AB  - Sphingomyelin, which has been degraded at the BHK cell surface by exogenous
      sphingomyelinase, is converted back into sphingomyelin with kinetics similar to
      those of plasma membrane recycling. Resynthesis of sphingomyelin under these
      conditions proceeds at a rate about 4-fold higher than normal biosynthesis of
      sphingomyelin. Neither resynthesis of sphingomyelin nor its return to the surface
      is inhibited by brefeldin A (BFA), which is a potent blocker of vesicular
      transport through the Golgi but has no effect on plasma membrane recycling.
      However, resynthesis of plasma membrane sphingomyelin is greatly decreased in
      cells undergoing mitosis or energy depletion, where endocytosis is inhibited. We
      conclude that the main site of surface sphingomyelin synthesis in BHK cells could
      be in recycling endosomes and not in the Golgi apparatus as proposed previously.
      We also suggest a model pathway by which cholesterol may reach the plasma
      membrane via recycling endosomes.

PMID- 8155685
TI  - Re-examination of hexose exchanges using rat erythrocytes: evidence inconsistent
      with a one-site sequential exchange model, but consistent with a two-site
      simultaneous exchange model.
AB  - (1). The kinetic parameters of zero-trans net uptake and infinite-trans uptake of
      3-O-methyl-D-glucoside, 2-deoxy-D-glucose and D-mannose into rat red cells at 24
      degrees C were measured after taking account of the linear diffusion components
      of flux. (2). Zero-trans exists of 3-O-methyl-D-glucoside and D-mannose from rat
      cells were also measured. (3). After correction for linear flux via non-specific
      routes, the Vmax of zero-trans uptake of 3-O-methyl-D-glucoside was significantly
      higher, (1.25 +/- 0.06 mumol (10 min)-1 (ml cell water)-1) than the corresponding
      parameters of mannose or 2-deoxy-D-glucose, (0.33 +/- 0.01 and 0.39 +/- 0.01
      mumol(10 min)-1 (ml cell water)-1, respectively; P < 0.001). (4). After
      correction for linear flux via non-specific uptake routes, the Vmax of zero-trans
      exit of 3-O-methyl-D-glucoside is significantly higher (1.70 +/- 0.1 mumol (10
      min)-1 (ml cell water)-1) than the corresponding value for mannose exit flux,
      (1.10 +/- 0.1 mumol (10 min)-1 (ml cell water)-1; P < 0.001). (5). The
      acceleration ratio, i.e., the ratio of infinite-trans influx Vmax/zero-trans
      influx Vmax of mannose by mannose (9.12 +/- 0.03) is significantly higher than
      that of 3-O-methyl-D-glucose by 3-O-methyl-D-glucose (2.77 +/- 0.14)(P < 0.001).
      (6). The one-site simple carrier model of glucose transport in which sugar
      exchange is viewed as a sequential process, predicts that the acceleration ratio
      of the more rapidly moving sugar 3-O-methyl-D-glucose by 3-O-methyl-D-glucose
      should be greater than that of the slower sugar, mannose by mannose. Hence, the
      observed findings are inconsistent with the one-site model, but confirm the
      earlier disputed studies of Miller, D.M. (1968; Biophys. J. 8, 1329-1338). (7). A
      two-site model, in which sugar exchange is considered as a simultaneous process,
      predicts that the acceleration ratio of mannose influx by mannose should be
      higher than for 3-O-methyl-D-glucose by 3-O-methyl-D-glucose. The data are,
      therefore, consistent with a two-site model.

PMID- 8155686
TI  - Transport mechanisms responsible for the absorption of loracarbef, cefixime, and
      cefuroxime axetil into human intestinal Caco-2 cells.
AB  - Loracarbef, cefixime and cefuroxime axetil are beta-lactam antibiotics that are
      administered orally. Oral absorption of loracarbef is nearly complete, while that
      of cefixime and cefuroxime axetil is 30-50%. To investigate this we used the
      human intestinal cell line Caco-2 that possesses the proton-dependent peptide
      transporter that takes up cephalexin and cefaclor. Drug uptake was measured at pH
      6 by high performance liquid chromatography or with radioactively labelled drug.
      The initial uptake rate of 1 mM cefixime was lower than that of 1 mM loracarbef.
      By 2 h both drugs were concentrated intracellularly against a gradient; however,
      the accumulation of cefixime was only 40% of that of loracarbef. The uptake rate
      of both drugs was sodium-independent, temperature- and energy-dependent, and was
      inhibited by dipeptides, cephalexin, cefaclor, but not by amino acids. Kinetic
      analysis of the concentration-dependence of the uptake rates for loracarbef and
      cefixime indicated that diffusion and a single transport system were responsible
      for uptake. The kinetic parameters for loracarbef and cefixime, respectively,
      were: Km values of 8 and 17 mM and Vmax values of 6.5 and 2 nmol/min per mg
      protein. Loracarbef and cefixime were competitive inhibitors of each other's
      uptake. By contrast, cefuroxime axetil was taken up and rapidly hydrolyzed to
      cefuroxime by Caco-2 cells. Cefuroxime axetil uptake was not dependent on energy
      and was not affected by dipeptides. Thus, cefuroxime axetil apparently enters
      Caco-2 cells by simple diffusion. By contrast, loracarbef and cefixime share a
      common transport mechanism, the proton-dependent dipeptide transporter. Cefixime
      was taken up less well than loracarbef due to a substantial reduction in the
      turnover rate and decreased affinity of the transporter for cefixime.

PMID- 8155687
TI  - Theoretical study of the complexation of amphotericin B with sterols.
AB  - The aim of this present work was the study of the intermolecular complexes
      between amphotericin B (AmB) and either cholesterol or ergosterol. In such
      complexes the intermolecular interaction energy mainly proceeds from both Van der
      Waals and H-bonding (via water molecules) forces. Our calculations have shown
      that the Van der Waals forces slightly favor the AmB-ergosterol complex. Several
      relative positions of the sterol with regard to AmB lead to energy minima: sterol
      may be either in contact with the AmB polar head or repelled towards the end of
      the macrolide ring. It appeared that the role played by some water molecules was
      to maintain the sterol close to the AmB polar head.

PMID- 8155688
TI  - Solubilization and molecular characterization of the nitrobenzylthioinosine
      binding sites from pig kidney brush-border membranes.
AB  - The nitrobenzylthioinosine binding sites from luminal membranes of proximal
      tubule of pig kidney were solubilized by treatment of the brush-border membrane
      vesicles with the zwitterionic detergent CHAPS (3-[(3
      cholamidopropyl)dimethylammonio]-1-propane sulfonate) in 2% solution. The high
      yield solubilization of a stable form of the transporter took place in the
      presence of adenosine in the medium of incubation with the detergent and the
      additional presence of glycerol as stabilizer. The solubilization of the NBTI
      sensitive nucleoside transporter from pig kidney brush-border membranes did not
      change the nitrobenzylthioinosine (NBTI) binding characteristics; the only major
      change was a 3-fold decrease in the affinity. The carrier molecule was cross
      linked to [3H]NBTI and by electrophoretic characterization under reducing
      conditions it displayed a molecular mass of 65 kDa. Treatment of the samples at
      low temperature prior to electrophoresis gave rise to the appearance of further
      bands corresponding to dimeric and tetrameric forms which interacted non
      covalently. The removal of the N-linked oligosaccharides by treatment with
      endoglycosidase F shifted the molecular mass to 57 kDa. The chromatographic
      behaviour of the solubilized transporter was similar to that of human
      erythrocytes and differed from that found in pig erythrocytes. Since the
      molecular mass of the monomer before and after treatment with endoglycosidase F
      is the same for pig erythrocytes and pig kidney luminal membranes, the different
      chromatographic behaviour might result from tissue differences due to
      transcriptional variations or to posttranscriptional modifications of the
      transporter molecule.

PMID- 8155689
TI  - Ascorbate function at the plasma membrane.

PMID- 8155690
TI  - Blood group antigens on human erythrocytes-distribution, structure and possible
      functions.
AB  - Human erythrocyte blood group antigens can be broadly divided into carbohydrates
      and proteins. The carbohydrate-dependent antigens (e.g., ABH, Lewis, Ii, P1, P
      related, T and Tn) are covalently attached to proteins and/or sphingolipids,
      which are also widely distributed in body fluids, normal tissues and tumors.
      Blood group gene-specific glycosyltransferase regulate the synthesis of these
      antigens. Protein-dependent blood group antigens (e.g., MNSs, Gerbich, Rh, Kell,
      Duffy and Cromer-related) are carried on proteins, glycoproteins and proteins
      with glycosylphosphatidylinositol anchor. The functions of these molecules on
      human erythrocytes remain unknown; some of them may be involved in maintaining
      the erythrocyte shape. This review describes the distribution, structures and
      probable biological functions of some of these antigens in normal and
      pathological conditions.

PMID- 8155691
TI  - Specificity of transporters for 'organic anions' and 'organic cations' in the
      kidney.

PMID- 8155692
TI  - Annexins: the problem of assessing the biological role for a gene family of
      multifunctional calcium- and phospholipid-binding proteins.

PMID- 8155693
TI  - Memories of metallothionein.
AB  - Metallothionein (MT) has provided nature with a small molecule which exhibits
      multiple facets. The distinct arrangement of cysteine residues which occurs
      within the two domains of MT confers predisposed metal specificity upon each
      domain. Furthermore, subtle changes in primary sequence may be built onto the
      metal cluster scaffold. These not only bestow immunodistinction but may also
      potentially allow specific members of this family such as MT-III to fulfill
      unique biological roles. An understanding of how the structures of MT molecules
      predetermine their biochemical characteristics may allow the design of novel
      metal-binding molecules specific for the metal ion of choice. Already, using
      nature as a blueprint, a semi-specific cadmium-binding molecule has been
      constructed from a polymer of mammalian C-terminal domains. This novel protein
      has been used to protect tobacco plants from cadmium toxicity. In addition,
      modeling of biologically active determinants which are located on the external
      face of MT-III may facilitate the design of small synthetic molecules which mimic
      the biological activity of MT-III and prevent the distressing effects of memory
      and speech loss associated with Alzheimer's disease. Memories of metallothionein
      may yet be something worth remembering!

PMID- 8155694
TI  - Involvement of lysine residues of goat serum albumin in high-affinity binding of
      bilirubin.
AB  - Four maleylated derivatives of goat serum albumin having percent modification as
      40%, 46%, 84% and 98% were prepared using varying molar ratio of maleic anhydride
      over protein. These preparations were found to be pure, both with respect to size
      and charged as judged by gel filtration and polyacrylamide gel electrophoresis.
      Maleylation caused significant change in protein conformation as revealed by the
      change in Stokes radius and frictional ratio of serum albumin, from 3.46 nm and
      1.28 to 4.96 nm and 1.79, respectively, upon 98% modification. Immunodiffusion
      results of native and modified albumins with anti-goat serum albumin antiserum
      also suggested significant conformational changes in serum albumin upon
      maleylation. About 88% reduction in bilirubin binding was observed after
      modification of 98% amino groups of serum albumin as studied by visible
      difference spectroscopy at pH 8.0, and at 0.15 ionic strength. Increase in ionic
      strength to 1.0 did not lead to any significant reversal in bilirubin binding.
      These results prove the involvement of lysine residues in bilirubin-albumin
      interaction.

PMID- 8155695
TI  - High-affinity binding of two molecules of warfarin and phenprocoumon to human
      serum albumin.
AB  - Binding equilibria of warfarin, 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin, and
      phenprocoumon, 3-(alpha-ethylbenzyl)-4-hydroxycoumarin, to defatted human serum
      albumin (Kabi Vitrum) were studied by equilibrium dialysis in a 33 mM sodium
      phosphate buffer (pH 7.4) at 37 degrees C. The binding data were analysed in
      terms of several acceptable sets of binding constants using a computerized curve
      fitting procedure. The findings were consistent with binding of two warfarin or
      two phenprocoumon molecules with high affinity and additional molecules bound
      with lower affinity. The binding of warfarin or phenprocoumon was explained by a
      model with two independent and equal high-affinity binding sites besides several
      independent weak sites in the albumin molecule (p < 0.01, by F-test). The
      findings were not consistent with binding of warfarin or phenprocoumon to a
      single high-affinity site besides several weak sites. A model of sequential
      binding of several ligand molecules to one locus is proposed.

PMID- 8155696
TI  - Specificity of chitosanase from Bacillus pumilus.
AB  - Partially (25-35%) N-acetylated chitosan was digested by chitosanase from
      Bacillus pumilus BN-262, and structures of the products, partially N-acetylated
      chitooligosaccharides, were analyzed in order to investigate the specificity of
      the chitosanase. The chitosanase produced glucosamine (GlcN) oligosaccharides
      abundantly, indicating that the chitosanase splits the beta-1,4-glycosidic
      linkage of GlcN-GlcN. The chitosanase also produced hetero-oligosaccharides
      consisting of glucosamine and N-acetyl-D-glucosamine (GlcNAc). Three types of the
      hetero-oligosaccharides purified by cation-exchange chromatography and HPLC were
      found to have GlcNAc residue at their reducing end and GlcN residue at their non
      reducing end, indicating that the chitosanase can also split the linkage of
      GlcNAc-GlcN. The determination of the mode of action toward partially N
      acetylated chitosan enables a classification of chitosanases according to their
      specificities and a more precise definition of chitosanases.

PMID- 8155697
TI  - Single-step affinity purification, partial structure and properties of human
      platelet cGMP inhibited cAMP phosphodiesterase.
AB  - The human platelet cilostamide- and cGMP-inhibited cAMP phosphodiesterase (cGI
      PDE) was rapidly purified approximately 19,000-fold to apparent homogeneity using
      single step affinity chromatography on the isothiocyanate derivative of
      cilostamide coupled to aminoethyl agarose. Within 24 h, 30 micrograms of enzyme
      protein was obtained from 20 ml of packed platelets. Vmax for cAMP and cGMP was
      6.1 and 0.9 mumol/min per mg protein, respectively. Several polypeptides
      (110/105, 79, 62, 55/53 kDa) were identified after SDS-PAGE, all of which were
      immunologically related to cGI-PDE and represented approx. 5, 20, 50 and 20% of
      the total protein, respectively. Limited proteolysis of the cGI-PDE with
      chymotrypsin produced a major fragment of approximately 47 kDa (and at least two
      smaller peptides) with catalytic activity and sensitivity to cGMP and OPC 3911
      similar to controls. Phosphorylation of the cGI-PDE by cAMP-dependent protein
      kinase (A-kinase) resulted in maximal incorporation of 0.6-1.8 mol of 32P/mol
      110/105 and 79 kDa polypeptides; much lower and variable amounts of phosphate
      were incorporated into the 62 and 55/53 kDa polypeptides. After digestion of cGI
      PDE with several proteinases a number of peptides were isolated and sequenced.
      Most of the peptide sequences obtained could be aligned within the carboxy
      terminal domain of the deduced sequence of the human cardiac cGI-PDE. These and
      other results suggest that the subunit size of the intact platelet cGI-PDE is 110
      kDa and that proteolytic fragments of 79, 62 and 55/53 kDa are produced during
      purification. The smaller fragments (62 and 55/53 kDa) contain the catalytic
      domain; the larger fragments (110 and 79 kDa) also contain the regulatory domain
      with phosphorylation sites for A-kinase.

PMID- 8155698
TI  - The reaction of cephalosporins with penicillin-binding protein 1b gamma from
      Escherichia coli.
AB  - The kinetics of the reaction of purified penicillin-binding protein 1b gamma from
      Escherichia coli with cephalosporins suggest that the enzyme exists in two
      kinetically distinct conformations that are in slow equilibrium. One of these
      forms can effect rapid hydrolysis of some beta-lactams and it is only through its
      deactivation by conversion to the slower reacting form that complete inhibition
      can be achieved. With some cephalosporins and with penicillins having simple
      aromatic side-chains the reaction was slower and did not exhibit the same kinetic
      behaviour. This could be attributed to the rate of reaction being similar to the
      rate of conformation change and thus sets an upper limit on the isomerization
      rate.

PMID- 8155700
TI  - Interdependence of phospholipid specificity and calcium binding in annexin I as
      shown by site-directed mutagenesis.
AB  - We have mutated the lysine 128 of domain II of annexin I, which flanks a putative
      calcium-binding loop, into a glutamic acid residue. The properties of the mutated
      recombinant protein were compared to those of the wild-type recombinant protein.
      A change in the isotherm of calcium binding in the presence of lipids was
      observed. A slight decrease in the affinity for lipids was evident. When tested
      for the vesicle aggregation property, the mutation induced a change in lipid
      specificity; unlike the wild-type protein, the mutant protein aggregates vesicles
      containing phosphatidylserine plus phosphatidylethanolamine better than vesicles
      containing only phosphatidylserine. These experiments are in agreement with a
      model which suggests that a lipid molecule is inserted into the calcium-binding
      loop of annexin I and that the conserved lysine residue is involved in the
      specificity of annexins for anionic phospholipids.

PMID- 8155699
TI  - Human placental aldose reductase: role of Cys-298 in substrate and inhibitor
      binding.
AB  - Steady-state kinetic and inhibition properties of human placental aldose
      reductase carboxymethylated at Cys-298 were investigated. A comparison of the
      primary deuterium kinetic isotope effect on the reduced and the carboxymethylated
      enzymes suggests that carboxymethylation did not affect the reaction sequence of
      substrate binding and release. Values of DV/KD-glyceraldehyde greater than DV
      suggest that steps in the reaction scheme subsequent to hydride transfer,
      particularly the release of NADP may be rate limiting. Carboxymethylation of Cys
      298 was also found to affect NADPH and aldehyde binding to the enzyme.
      Carboxymethylation had little effect on the secondary structure of the enzyme,
      but a comparison of the circular dichroic spectra of the reduced and
      carboxymethylated enzyme, suggests a weakened interaction between the
      nicotinamide and 2'-monophosphoadenosine 5'-diphosphoribose of NADPH, and the
      carboxymethylated enzyme. Interaction between Cys-298 and NADPH appears to
      determine the rate of isomerization of the E:NADP binary complex and
      carboxymethylation-induced decrease in kcat may be due to slower isomerization of
      the E:NADP binary complex. The carboxymethylated enzyme was less sensitive than
      the reduced enzyme to most aldose reductase inhibitors including sorbinil (d-6
      fluoro-spiro[chroman-4,4'-imidazolidine]-2',5'-dione), except tolrestat (N-methyl
      N-[(5-trifluromethyl-6-methoxy-1-naphthalenyl)- thiomethyl]glycine) and
      quercetin. On the basis of these observations it is suggested that Cys-298 may
      form a part of the 'S'-inhibitor binding site of the enzyme and may be
      responsible for tight binding of NADPH.

PMID- 8155701
TI  - Role of the TIGN sequence in E. coli tryptophanyl-tRNA synthetase.
AB  - Tryptophanyl-tRNA synthetase in E. coli does not have the HIGH sequence that is
      normally characteristic of class I aminoacyl-tRNA synthetases (EC 6.1.1.2), but
      instead contains a TIGN sequence at residues 17-20, which has been suggested to
      be equivalent to the HIGH sequence (Jones, M.D. et al. (1986) Biochemistry 25,
      1887-1891). We have overexpressed E. coli Trp-tRNA synthetase and have used site
      directed mutagenesis to mutate Thr-17 in the TIGN sequence to alanine. The mutant
      enzyme has the same Km values as the wild-type for tryptophan or tRNA(Trp), and a
      slightly increased Km for ATP, from 0.37 to 0.64 mM. On the other hand, the kcat
      for either the first step or the overall reaction is decreased by a factor of 30.
      In comparing the Thr-17 and Ala-17 enzymes, the delta delta G for the conversion
      of substrate to transition state is +9.6 kJ/mol (2.3 kcal/mol). Thr-17 is
      therefore important in binding the substrate in the transition state, thus
      supporting the suggestion that TIGN may fulfill the role of a HIGH sequence.

PMID- 8155702
TI  - Kinetic evaluation of the oxidation of phenothiazine derivatives by methemoglobin
      and horseradish peroxidase in the presence of hydrogen peroxide. Implications for
      the reaction mechanisms.
AB  - The oxidation of ten 2-substituted 10-(3-(dimethylamino)propyl) phenothiazines
      (PHs) by methemoglobin (metHb) and horseradish peroxidase (HRP) in the presence
      of H2O2 was kinetically analysed based on an enzymic-chemical second-order
      reaction with substrate regeneration: PHs are oxidized enzymatically to their
      radical cations (PH+) which subsequently, in a second order reaction, react
      further to parent compound and PH-sulfoxide (PHSO). The enzymic reaction rate can
      be obtained from the accumulation curves of both radical cation formation and
      sulfoxide formation. In the case of chlorpromazine and promazine both methods
      gave similar reaction rates. The rate constant of PH+. decay could also be
      determined from the radical concentrations of their radicals. The rate constant
      of reaction of PHs with HRP compound II was also analysed. The logarithm of this
      rate constant correlated well with the Hammett sigma para and the Swain and
      Lupton F and R substituent constants, whereas no correlation with hydrophobic and
      steric parameters was found. This indicates that the interaction of PH with the
      porphyrin ring, which is the active site of HRP, is predominantly under
      electronic control. In the case of catalysis by hemoglobin (Hb), the formation of
      the reactive Hb form, ferry1Hb with a protein radical, appeared to be rate
      limiting in the oxidation of PHs by metHb-H2O2. Differences in the conversion
      rates of various PHs can be explained by a competition between their electron
      transfer reaction to the protein radical and the denaturation reaction(s)
      involving the protein radical. Our results confirm our earlier observation that
      the mechanism of oxidation by metHb-H2O2 differs from that of the classical
      peroxidases. In the former case, electron transfer from PH occurs most likely to
      a tyrosine residue on the globin part, whilst in the latter case electron
      transfer to the porphyrin moiety takes place.

PMID- 8155703
TI  - Conformational changes upon dissociation of a globular protein from pea: a
      Fourier transform infrared spectroscopy study.
AB  - Fourier transform infrared spectroscopy shows that the secondary structure of
      legumin, a globular protein from pea seeds, is composed of 41% beta-sheets and
      16% alpha-helices and furthermore reveals the presence of beta-turns. The
      conformation prediction from the analysis of the amino-acid sequence of legumin
      using hydrophobic cluster analysis reveals that the C-terminal part of the alpha
      polypeptide is devoid of defined secondary structures, whereas the beta
      polypeptide is highly ordered. Comparison with analogous 11S globulins from other
      plant families indicates that ordered domains are highly preserved, phenomenon
      that may be associated with the similarity of the quaternary structure of these
      proteins. The results also reveal the presence of a large hypervariable region,
      located at the surface of the protein, that could be at the origin of the
      different functional properties of the 11S type globulins. The step-by-step
      destruction of the quaternary oligomeric structure of the native protein is
      accompanied by conformational changes that depend on the dissociation conditions.
      Whereas acylation leads to a decrease of the alpha-helix content by 10% at the
      expense of the beta-sheet content, addition of sodium perchlorate results in the
      conversion of 10% of the protein secondary structure from beta-sheet to
      unordered. These observations provide further evidence of the existence of
      different monomeric states that differ from their secondary structure and,
      therefore, exhibit different surface-active properties.

PMID- 8155704
TI  - Alteration of tryptophan fluorescence properties upon dissociation of Lumbricus
      terrestris hemoglobin.
AB  - Fluorescence analysis has been used to study dissociation of the dodecameric 3.8
      kDa Lumbricus terrestris hemoglobin. Since tryptophan intrinsic fluorescence has
      been used as a reporter group to study Lumbricus hemoglobin, it is of interest to
      study dissociation perturbed properties of the tryptophan residues. Shifts in the
      fluorescence emission maximum to longer wavelengths upon dissociation at pH 9.2
      suggest that tryptophans buried at the subunit interface(s) become more exposed.
      Fluorescence lifetime and quenching studies are employed in this present
      investigation as a means to confirm the location of tryptophan residues at the
      subunit interfaces. Acrylamide titration (to 2.5 M) indicate only a fraction of
      the residues can be quenched at either pH. At pH 7.0, the Stern-Volmer plot has
      downward curvature, while at pH 9.2 there is slight upward curvature, again
      indicating a change in environment. The intrinsic fluorescence decay requires at
      least four exponentials at both pHs. The mean fluorescence lifetime of CO
      Lumbricus hemoglobin increases from 1.1 ns at pH 7 to 3.3 ns at pH 9.2. The
      lifetime data can be further interpreted as a decrease in the quenching of
      residues with a approximately 30 ps lifetime, and a concomitant increase in the
      longer lifetime components. This is consistent with interface tryptophans
      becoming exposed to solvent upon dissociation, and loss of quenching by
      intersubunit hemes. The overall results suggest that in the dodecamer, most of
      the tryptophans are located in a hydrophobic environment, not all of which are
      located at the subunit interface.

PMID- 8155705
TI  - Cyanide dissociation from the hemoglobin of Parascaris equorum.
AB  - The reduction of cyanomethemoglobin by dithionite leads to the appearance of an
      intermediate, the complex of cyanide with ferrous hemoglobin, whose dissociation
      is easily followed in a stopped flow apparatus. This reaction was studied in the
      hemoglobin from the parasitic nematode Parascaris equorum, whose extremely high
      oxygen affinity is due to a very low dissociation rate. The rate of cyanide
      dissociation from ferrous Parascaris hemoglobin is not so dramatically different
      from that of other hemoglobins and myoglobins. Other features of the reaction
      are: (i) the rate constant of cyanide release is pH independent, an observation
      which is agreement with the possible absence of the distal histidine, given the
      mechanism suggested in a previous study (Bellelli, A., Antonini, G., Brunori, M,
      Springer, B.A. and Sligar, S.G. (1990) J. Biol. Chem. 265, 18898-18901), and (ii)
      the time-course shows no kinetic cooperativity. The structural basis of the
      extremely high oxygen affinity of Parascaris hemoglobin cannot be explained on
      the basis of the results here reported. This study also confirms that, even
      though cyanide binding to ferrous hemoglobins is controlled by distal
      interactions, the functional behaviour of this ligand is characteristic and
      differs from the behaviour of oxygen.

PMID- 8155706
TI  - Different effect of 5,6-trans-prostaglandin E2 on plasminogen activation by
      urokinase and streptokinase.
AB  - We examined the effects of 5,6-trans-prostaglandin E2 (trans-PG E2) on
      fibrinolysis and plasminogen activation by either urokinase or streptokinase.
      trans-PG E2 was found to enhance fibrinolysis induced by urokinase and inhibit
      the one by streptokinase. These effects were also appeared in the method using
      synthetic chromogenic substrate S-2251, which suggested that the effects of trans
      PG E2 were induced in the circumstances without coagulation factors such as
      fibrinogen, thrombin or fibrin. Moreover, the enhancement effect of trans-PG E2
      on fibrinolysis by urokinase was investigated. The result of SDS-PAGE indicated
      that plasmin formation rate from plasminogen by urokinase was accelerated in the
      presence of trans-PG E2. As trans-PG E2 increased the hydrolyzing rate of S-2288
      by urokinase, trans-PG E2 directly interacted with urokinase. Therefore, the
      enhancement effect of trans-PG E2 on plasminogen activation by urokinase could be
      explained, at least in part, as follows: at first trans-PG E2 directly exerts its
      effect on urokinase, then it causes the increase of generation rate of plasmin
      from plasminogen.

PMID- 8155707
TI  - Influence of bulky side chains of amino acids on the solution conformation of
      peptide fragment (81-92) derivatives of CD4, TYICEVEDQKEE, as studied by NMR
      spectroscopy and molecular modeling.
AB  - Solution conformation of CD4 fragment 81-92 TYICEVEDQKEE and two of its
      benzylated analogues was determined by two-dimensional 1H NMR spectroscopy,
      distance geometry and simulated annealing techniques. The structures of both
      benzylated derivatives are similar but are distinct from that of wild-type
      dodecapeptide. It is concluded from structural analysis that bulky side chain(s)
      of amino acid(s) at an appropriate position can have a marked effect on the
      conformation and thus the functions of a peptide.

PMID- 8155708
TI  - Analysis of progress curves for enzyme-catalyzed reactions: application to
      unstable enzymes, coupled reactions and transient-state kinetics.
AB  - There are several advantages to the use of progress curves to analyze the the
      kinetic properties of enzymes but most studies still rely on rate measurements.
      One of the reasons for this may be that progress curve analysis relies on the
      enzyme and the reactants being completely stable under assay conditions. Here a
      method is described that relaxes this requirement and allows progress curve
      analysis to be applied to unstable enzymes. The procedure is based on a
      combination of numerical integration and non-linear regression to fit rate
      equations to the progress curve data. The analysis is verified using simulated
      data and illustrated by application to the reaction catalyzed by alkaline
      phosphatase, measured in the presence of 10 mM EGTA where it has a half-life of 3
      1/2 min. The method may also be applied to other experimental systems where the
      development over time reveals important properties but where an analytical
      solution of the underlying model is not known. This extension is illustrated by
      two systems: the coupled reactions catalyzed by pyruvate kinase and lactate
      dehydrogenase under conditions where both enzymes have similar activity; and the
      transient-state kinetics of the reaction catalyzed by glutamate dehydrogenase.

PMID- 8155709
TI  - Lactoferrin contains structural motifs of ribonuclease.
AB  - A high molecular weight ribonuclease isolated from human milk (hmRNAase) shares
      identical immunological, physical, structural features and considerable sequence
      homology with human lactoferrin; and it has been demonstrated to be an isoform of
      lactoferrin. We have analyzed the sequence data of lactoferrin looking for the
      existence of specific features corresponding to the consensus sequence of
      pyrimidine-specific ribonucleases. The analysis was done by comparing sequence
      features with respect to elements which are, in principle, responsible for RNAase
      activity. This revealed the existence of a ribonuclease-signature pattern in
      lactoferrin. Further analysis of X-ray data together with molecular modeling
      studies have revealed close similarities between the spatial geometry of the
      constituent groups of the active site of pyrimidine-specific ribonucleases and
      the corresponding groups comprising the potential active site of lactoferrin. Our
      results provide the strong structural basis for the existence of ribonuclease
      activity in lactoferrin.

PMID- 8155710
TI  - The effect of pH on the suicide inactivation of frog epidermis tyrosinase.
AB  - This paper presents a new reaction mechanism for the effect of the pH on the
      suicide inactivation of the diphenolase activity of tyrosinase. The applicability
      of the mechanism is supported by the experimental characterization of the kinetic
      behaviour of the frog epidermis enzyme acting on catechol, L-dopa and alpha
      methyldopa at several pH values. Two enzyme froms 'met-' and 'oxy-' tyrosinase,
      but no their corresponding enzyme-diphenol complexes, present one ionizable group
      with very similar value of Ka which has been determined. The highest values of
      catalytic and inactivation efficiencies correspond to alpha-methyldopa and
      catechol, respectively. These kinetic studies have been carried out by using the
      transient phase approach previously developed, with negligible substrate
      consumption during the assay time. That illustrate the usefulness of the method
      for multisubstrate enzyme reactions.

PMID- 8155712
TI  - Movement of the F40 domain of flagellin during the morphological transition of
      bacterial flagella.
AB  - Flagella from Salmonella typhimurium were labeled with various amounts of
      fluorescein isothiocyanate. The site of labeling was identified as being
      predominantly in the exterior F40 domain. The fluorescence intensity decreased as
      the fluorescein density on the flagella increased, indicating self energy
      transfer between fluoresceins. The fluorescence of modified flagella was measured
      during the normal-to-curly morphological transition induced by alkaline pH. The
      morphological transition itself was simultaneously monitored by dark-field
      microscopy. Concomitant with the transition was a 25% increase in fluorescence
      for flagella heavily labeled with fluorescein. This was shown to be due to a
      decrease in the efficiency of energy transfer between fluoresceins on proximal
      flagellin subunits, implying that the F40 domains undergo relative movement apart
      during the morphological transition. Closer inspection of the domain movement and
      morphological transition as a function of pH reveals that the two processes are
      not exactly concomitant. This indicates the existence of intermediates during the
      transition. The fluorescence technique, outlined here, provides a means of
      directly monitoring an organizational 'switch' in the flagellin subunits during
      the actual morphological transition of flagella.

PMID- 8155711
TI  - Active-site residues of procarboxypeptidase Y are accessible to chemical
      modification.
AB  - The accessibility of the active-site cleft of procarboxypeptidase Y from
      Saccharomyces cerevisiae has been studied by chemical modifications of two
      specific amino-acid residues. Previous studies have shown that these residues,
      Cys-341 and Met-398 in the mature enzyme, are located in the S1 and S'1 substrate
      binding sites, respectively, of carboxypeptidase Y. We have found that these
      residues also in proCPY are accessible to modification with fairly bulky reagents
      and in the case of Met-398 the rate of modification is even faster than in
      carboxypeptidase Y. While the catalytic serine in the mature enzyme reacts with
      diisopropylfluorophosphate, this is not the case for procarboxypeptidase Y.

PMID- 8155713
TI  - Human liver aldehyde dehydrogenases: new method of purification of the major
      mitochondrial and cytosolic enzymes and re-evaluation of their kinetic
      properties.
AB  - A new purification procedure, based on dye-adsorption and affinity
      chromatography, has been developed for the isolation of the two major ALDH
      isozymes from human liver: ALDH-1 (cytosolic, pI 5.2) and ALDH-2 (mitochondrial,
      pI 4.9). The procedure affords milligram quantities of ALDH-1 and -2 at 850- and
      275-fold purifications, respectively, from 50 g of liver in two days. Kinetic
      parameters for acetaldehyde oxidation were determined with these purified
      enzymes, because there is a wide discrepancy in the absolute magnitude of these
      parameters in the biochemical literature. The Michaelis constants for ALDH-1 and 
      2, determined from initial velocities (for ALDH-1) and single reaction progress
      curves (for ALDH-2), are 180 +/- 10 microM and 0.20 +/- 0.02 microM, respectively
      (pH 7.5 and 9.5, saturating NAD+ in both cases). This three orders of magnitude
      difference in Km values is much greater than that reported previously in all but
      one study.

PMID- 8155714
TI  - Cation binding to chicken gizzard alpha-actinin.
AB  - Gizzard alpha-actinin binds 45Ca2+ as shown by the calcium overlay method. Flow
      dialysis measurements in 20 mM Hepes (pH 7.5) reveal 3.5 +/- 1.8 (S.D.) high
      affinity calcium binding sites per dimer, with Kd1 = 6.36 +/- 0.34 x 10(-6) M,
      and 87.3 +/- 7.2 sites with Kd2 = 1.66 +/- 0.44 x 10(-4) M. Chymotrypsin and
      thermolysin digestion yielded peptides of gizzard alpha-actinin which, if they
      included the putative EF-hands, bound 45Ca2+ in 10 mM imidazole-HCl (pH 7.4) or
      60 mM KCl, 10 mM imidazole-HCl (pH 7.4). In addition, peptides which include a
      region of the molecule more than 27 kDa from the N-terminal also bind calcium. In
      contrast, when KCl in the binding buffer was increased to 120 mM, calcium binding
      was eliminated. Flow dialysis data revealed no high-affinity binding and 82.5 +/-
      3.3 calcium binding sites with calculated affinities in the millimolar range.
      These are divalent cation binding sites, not Ca(2+)-specific sites, because they
      are eliminated by the addition of up to 5 mM Mg2+. Structural changes produced
      upon cation binding to alpha-actinin measured by circular dichroism, proteolysis
      and bisANS fluorescence are substantial when binding K+ with only small changes
      upon binding of Ca2+ or Mg2+ in the presence of 120 mM KCl. These results suggest
      that monovalent and divalent cations have different effects on different parts of
      the molecule with a complete elimination of 45Ca2+ binding to the EF-hands being
      produced by 120 mM KCl.

PMID- 8155715
TI  - The kinetic studies on the intramolecular SH, S-S exchange reaction of bovine
      mercaptalbumin.
AB  - Bovine mercaptalbumin (BMA) has 17 disulfide bonds and one SH group at Cys-34
      which catalyzes the intramolecular SH, S-S exchange reaction (N-A isomerization,
      molecular aging) in the alkaline region at low ionic strength, resulting in the
      formation of the aged form (A-form). The aging reaction was completely reversible
      and strongly affected by environmental factors, such as pH, temperature, ionic
      strength, Ca2+, nonbranched short-chain fatty acids, etc. Disulfide configuration
      (or pairing of disulfide bonds) was affected by the environmental factors.
      Obtained results might support the concept of Klotz (1966) that protein
      conformation (or three-dimensional structure) is dependent upon (i) the primary
      structure and (ii) constituents of the solvent.

PMID- 8155716
TI  - Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P-450s to
      different flavonoids.
AB  - The inhibitory and stimulatory effects of six flavonoids with distinct
      hydroxylation patterns on the recombinant and hepatic mouse and human CYP1A P
      450s were studied. cDNA-expressed mouse CYP1A1 and CYP1A2 differed in their
      sensitivity to both hydroxylated and nonhydroxylated flavonoids, respectively. A
      comparison between the mouse and human CYP1A2 revealed that alpha-naphthoflavone
      and flavone did not change the benzo[a]pyrene 3-hydroxylation activity of human
      CYP1A2 but inhibited its 7-ethoxyresorufin and 7-methoxyresorufin O-dealkylation
      activities. In contrast, hydroxylated flavonoids increased the 7-methoxyresorufin
      O-demethylation and acetanilide 4-hydroxylation activities of cDNA-expressed
      human CYP1A2 and in human liver microsomes. These compounds inhibited the
      benzo[a]pyrene 3-hydroxylase activity of cDNA-expressed CYP1A1 and CYP1A2s as
      well as in mouse and human liver microsomes. Hydroxylated flavonoids did not
      inhibit NADPH-cytochrome P-450 oxidoreductase activity but inhibited NADPH-2,6
      dichlorophenolindophenol oxidoreductase activity in liver microsomes and in
      microsomes from recombinant Hep G2 cells. Structure-activity relationships
      indicated the importance of hydroxyl groups in the 5- and 7-positions on the A
      ring of the flavane nucleus. These hydroxyl groups accounted for the inhibitory
      potency of chrysin on each of the activities of the expressed P-450s, while
      presence of a hydroxyl group at the 4'-position on the B ring decreased the
      inhibitory potency of naringenin compared to that of chrysin. The ortho
      orientation of a hydroxyl group on the B ring was of importance, inasmuch as
      quercetin was more potent than morin as an inhibitor of cDNA-expressed and
      hepatic microsomal monooxygenases.

PMID- 8155718
TI  - Lipoxin biosynthesis and its impact in inflammatory and vascular events.

PMID- 8155717
TI  - Photoaffinity labeling for evaluation of uridinyl analogs as specific inhibitors
      of rat liver microsomal UDP-glucuronosyltransferases.
AB  - The UDP-glucuronosyltransferases (UGT) involved in glucuronidation of endogenous
      and exogenous toxic compounds transfer the glucuronic acid residue from UDP
      glucuronic acid (UDP-GlcUA), to various acceptor groups. A series of compounds
      that contain N-acyl phenylaminoalcohol derivatives linked to uridine or
      isopropylideneuridine were tested as UGT inhibitors. The potency of these
      inhibitors was determined by studying their effect on the photoaffinity labeling
      of rat liver microsomal UGTs by two photoaffinity probes, [beta-32P]5-azido-UDP
      glucuronic acid (5N3UDP-GlcUA) and [beta-32P]5-azido-UDP-glucose (5N3UDP-Glc) and
      on the enzymatic formation of the two glucuronide conjugates (3-O- and carboxyl
      specific) of lithocholic acid. All but one of the compounds tested proved to have
      an inhibitory effect on UGTs, both in the photoaffinity labeling system and in
      the enzymatic glucuronidation assay. In the photoaffinity labeling system, the
      inhibitors containing the isopropylidene moiety were less effective than their
      unprotected derivatives; however, the protected forms were, with one exception,
      more potent inhibitors of enzymatic activity. The photoaffinity labeling of UGTs
      with [beta-32P]5N3UDP-Glc was more susceptible to inhibition by all derivatives
      than that with [beta-32P]5N3UDP-GlcUA. The effect of one inhibitor, PP50B, on the
      two enzymatic activities involved in LA glucuronidation was extensively tested. A
      double-reciprocal plot suggested a competitive inhibition for UDP-GlcUA with an
      apparent Ki of 35 microM for LA 3-O-glucuronide formation and 94 microM for the
      carboxyl-linked glucuronide of the same substrate.

PMID- 8155719
TI  - Nagase analbuminemic rats have faster plasma triacylglycerol and VLDL synthesis
      rates.
AB  - Serum triacylglycerol (TG) concentration is markedly elevated in Nagase
      analbuminemic rats (NAR) as compared to Sprague-Dawley rats (SDR) and reflects a
      high level of mainly VLDL. Hepatic production of triacylglycerol, as measured by
      the Triton-WR1339 infusion technique of impairing TG removal from blood, and
      plasma metabolic rate of pulse-infused [125I]apo VLDL, were higher in NAR.
      However, contrary to previous reports, this elevated TG production could not be
      controlled by previous treatment of NAR with (i) bovine albumin infused intra
      arterially or into the peritoneal cavity, or with (ii) dextran (Mol.wt. 73,500)
      injected intraperitoneally. Albumin administration expanded the plasma volume and
      could explain the apparent reduction of blood lipids found by others.
      Nonetheless, intraperitoneal dextran, as compared to saline, reduced the plasma
      cholesterol concentration regardless of the variation in the hematocrit level and
      thus, by raising the osmotic pressure of blood might regulate the metabolism of
      cholesterol-rich lipoproteins such as LDL and HDL in NAR.

PMID- 8155720
TI  - Phospholipid fatty acid composition and vitamin E levels in the retina of obese
      (fa/fa) and lean (FA/FA) Zucker rats.
AB  - We have compared the fatty acid composition of the major classes of phospholipids
      in the retina of lean (FA/FA) and genetically obese (fa/fa) male Zucker rats. In
      all phospholipid fractions, there was a higher ratio of n-3 to n-6 fatty acids in
      obese animals whereas the total content of polyunsaturated fatty acids (PUFA) was
      unaffected by the genotype. Lower percentages of arachidonic acid (20:4(n-6))
      were present in the phosphatidylcholine, phosphatidylinositol and
      phosphatidylserine fractions in the retina of obese rats. This was associated
      with a higher level of docosahexaenoic acid (22:6(n-3)) in these fractions. In
      addition, increased levels of dihomo-gamma-linolenic acid (20:3(n-6)) were
      present in the retinal phosphatidylcholine and phosphatidylethanolamine of obese
      animals. These results indicate that modifications of phospholipid fatty acid
      composition which have previously been reported in peripheral tissues of obese
      Zucker rats also affect the retina. Furthermore, the retinal levels of vitamin E
      were higher in obese than in lean rats suggesting differences in the tissue
      antioxidant status between these two genotypes.

PMID- 8155721
TI  - Role of processing of the oligosaccharide chains in the affinity of lipoprotein
      lipase for heparin.
AB  - The role of processing of the oligosaccharide chains in the affinity of
      lipoprotein lipase (LPL) for heparin was examined in 3T3-L1 adipocytes. 43% of
      35S-labeled LPL subunits in tunicamycin (TUN)-treated cells did not bind to a
      heparin-Sepharose column and 46% was eluted with 0.6 M NaCl. 11% of LPL subunits
      in castanospermine (CSTP)-treated cells did not bind to the column and 38% was
      eluted with 0.6 M NaCl. In contrast, as in untreated cells, LPL subunits in 1
      deoxymannojirimycin (dMM)-treated and swainsonine (SW)-treated cells almost all
      bound to the column and over 93% of the subunits bound were eluted with 1.5 M
      NaCl. Thus, core glycosylation and subsequent removal of the distal glucose
      residue from oligosaccharide chains of LPL in the endoplasmic reticulum (ER) is
      required for acquisition of a higher affinity for heparin.

PMID- 8155722
TI  - Destabilisation of lamellar dispersion of thylakoid membrane lipids by sucrose.
AB  - Employing negative-staining electron microscopy, convincing evidence has been
      obtained for the destabilisation of multilamellar organisation of aqueous
      dispersions of chloroplast thylakoid membrane lipids, to an inverted micellar
      structure under the influence of sucrose solution. The present study provides a
      new insight into the phase behaviour of a naturally existing galactolipid-rich
      lipid mixture consequent to interaction with a kosmotropic reagent.

PMID- 8155723
TI  - Cloning and expression in Escherichia coli of a cDNA coding for the oleoyl-acyl
      carrier protein thioesterase from coriander (Coriandrum sativum L.).
AB  - A cDNA for the oleoyl-acyl carrier protein (ACP) thioesterase (E.C. 3.1.2.14)
      from coriander seed endosperm (Coriandrum sativum) was isolated using a safflower
      oleoyl-ACP thioesterase cDNA probe. The coriander cDNA coded for a 42.3 kDa
      protein including a putative 40 amino acid plastid targeting transit peptide. The
      gene was expressed in Escherichia coli and the recombinant protein was isolated
      to homogeneity by alkyl-ACP affinity and anion-exchange chromatography. The pure
      protein showed a high thioesterase activity for oleoyl-ACP vs. other acyl-ACPs
      and therefore was identified as the coriander oleoyl-ACP thioesterase. Antibodies
      were raised against the recombinant protein and used to detect the coriander
      thioesterase in enriched endosperm fractions.

PMID- 8155724
TI  - Phosphatidylcholine breakdown and signal transduction.
AB  - PC hydrolysis by PLA2, PLC or PLD is a widespread response elicited by most
      growth factors, cytokines, neurotransmitters, hormones and other extracellular
      signals. The mechanisms can involve G-proteins, PKC, Ca2+ and tyrosine kinase
      activities. Although an agonist-responsive cytosolic PLA2 has been purified,
      cloned and sequenced, the agonist-responsive form(s) of PC-PLC has not been
      identified and no form of PC-PLD has been purified or cloned. Regulation of PLA2
      by Ca2+ and MAPK is well established and involves membrane translocation and
      phosphorylation, respectively. PKC regulation of the enzyme in intact cells is
      probably mediated by MAPK. The question of G-protein control of PLA2 remains
      controversial since the nature of the G-protein is unknown and it is not
      established that its interaction with the enzyme is direct or not. Growth factor
      regulation of PLA2 involves tyrosine kinase activity, but not necessarily PKC. It
      may be mediated by MAPK. The physiological significance of PLA2 activation is
      undoubtedly related to the release of AA for eicosanoid production, but the LPC
      formed may have actions also. There is much evidence that PKC regulates PC-PLC
      and PC-PLD and this is probably a major mechanism by which agonists that promote
      PI hydrolysis secondarily activate PC hydrolysis. Since no agonist-responsive
      forms of either phospholipase have been isolated, it is not clear that PKC exerts
      its effects directly on the enzymes. Although it is assumed that a
      phosphorylation mechanism is involved, this may not be the case, and regulation
      may be by protein-protein interactions. G-protein control of PC-PLD is well
      established, although, again, it has not been demonstrated that this is direct,
      and the nature of the G-protein(s) involved is unknown. In some cell types, there
      is evidence of the participation of a soluble protein, which may be a low Mr GTP
      binding protein. What role this plays in the activation of PC-PLD is obscure.
      Agonist activation of PC hydrolysis in cells is usually Ca(2+)-dependent, but the
      step at which Ca2+ is involved is unclear, since PC-PLD and PC-PLC per se are not
      influenced by physiological concentrations of the ion. Most growth factors
      promote PC hydrolysis and this is mainly due to activation of PKC as a result of
      PI breakdown. However, in some cases, PC breakdown occurs in the absence of PI
      hydrolysis, implying another mechanism that does not involve PI-derived
      DAG.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8155725
TI  - Isolation and characterization of addition products of alpha-tocopherol with
      peroxyl radicals of dilinoleoylphosphatidylcholine in liposomes.
AB  - alpha-Tocopherol was reacted with peroxyl radicals of phosphatidylcholine at 37
      degrees C in liposomes. The phospholipid-peroxyl radicals were generated by the
      reaction of 1,2-dilinoleoyl-3-sn-phosphatidylcholine with a free radical
      initiator, 2,2'-azobis(2,4-di-methylvaleronitrile), under air. One peak
      corresponding to the reaction products of alpha-tocopherol with
      phosphatidylcholine-peroxyl radicals was isolated by reversed-phase high
      performance liquid chromatography. Its structure was identified as a mixture of
      8a-(phosphatidylcholine-peroxy)-alpha-tocopherones: 1-[9-(8a-peroxy-alpha
      tocopherone)-10,12-octadecadienoyl]-2- linoleoyl-3-sn-phosphatidylcholine,1-[13
      (8a-peroxy-alpha-tocopherone )-9,11-octadecadienoyl]-2-linoleoyl-3-sn
      phosphatidylcholine, 1-linoleoyl-2-[9-(8a, peroxy-alpha-tocopherone)-10,12
      octadecadienoyl]-3-sn-pho sph atidylcholine and 1-linoleoyl-2-[13-(8a-peroxy
      alpha-tocopherone)-9,11-octadecadi enoyl]-3-sn- phosphatidylcholine. The results
      indicate that each alpha-tocopherol can trap two peroxyl radicals during the
      peroxidation of unsaturated phospholipid in liposomes.

PMID- 8155726
TI  - Competitive inhibition of lipolytic enzymes. X. Further delineation of the active
      site of pancreatic phospholipases A2 from pig, ox and horse by comparing the
      inhibitory power of a number of (R)-2-acylamino phospholipid analogues.
AB  - Two series of (R)-phospholipid analogues, each containing a n-propyl group at the
      C-1 position and various acylamino functions at the C-2 position have been
      synthesized and their inhibitory properties towards three mammalian pancreatic
      phospholipases A2 have been determined. The members of the first series of
      analogues all contained the zwitter-ionic phosphocholine headgroup which in the
      second series was replaced by the anionic phosphoglycol function. In the
      saturated 2-acylamino phospholipids the length of the acyl chain ranged from 8 to
      18 carbon atoms. The unsaturated 2-acylamino analogues possessed a chain length
      of 11 or 18 carbon atoms and contained one, two, three or four double bonds. For
      inhibitors with a saturated acylamino group, the phospholipases A2 from pig, ox
      and horse show a sharp optimum in inhibitory power Z for an acyl chain length of
      10 carbon atoms. The inhibitory behaviour of the unsaturated acylamino analogues
      is more complex: both the zwitter-ionic and the anionic inhibitors demonstrate an
      increase in Z with an increasing number of cis-double bonds but the degree of
      improvement is dependent on the position of the double bonds. Subsequently the
      influence of polar groups at carbon position 12 of the dodecanoylamino
      phospholipids on Z was analyzed. Substitution of the terminal methyl group by an
      OH-function lowers the inhibitory potency of the three enzymes by a factor of 4
      to 5 both in the phosphocholine and phosphoglycol series. Replacement of the
      methyl group by potentially charged functions (-NH2, -COOH) resulted in a
      complete loss of inhibitory properties. Blocking of the amino group and carboxyl
      function by t-butyloxycarbonylation and esterification, respectively, fully
      restored the inhibitory power. Finally we investigated how changes in the polar
      headgroup and the presence of aromatic rings at the C-1 or C-2 position
      influenced the inhibitory potency of the analogues.

PMID- 8155727
TI  - The purification of phytoene dehydrogenase from Phycomyces blakesleeanus.
AB  - The carotenogenic enzyme phytoene dehydrogenase has been purified from the
      C9carR21(-) (lycopene-accumulating) mutant of the filamentous fungus Phycomyces
      blakesleeanus. Solubilization of the membrane-bound enzyme with 1% Tween-60 was
      followed by a 250-fold purification to homogeneity using polyethylene glycol
      precipitation, CM-Sepharose, gel filtration and isoelectric focusing. Multiple
      peaks of enzymic activity were found in eluates from ion-exchange and gel
      filtration chromatography, with the lowest molecular weight fraction having an
      apparent molecular mass of approx. 14 kDa. All active fractions catalyzed the
      dehydrogenation of 15-cis phytoene into all-trans lycopene, with a cis-trans
      isomerization occurring at phytofluene. Both NADP+ and FAD were required for the
      dehydrogenation reaction. The presence of > 0.5% Tween-60 was necessary to
      maintain enzymic activity, although in its absence lipids restored some activity.
      The enzyme could be stored for at least 6 weeks at -70 degrees C in the presence
      of 20% (v/v) glycerol.

PMID- 8155728
TI  - Probing of active site structure of lipoprotein lipase: contribution of
      activation entropy in the catalysis.
AB  - In this study, I have utilized the chromogenic short-chain esters of p
      nitrophenol as substrates for probing the active site structure of lipoprotein
      lipase (LPL). The results indicated that there is a consistent trend in the
      decrease of the Michaelis-Menten constant with increase of the acyl-chain length.
      Therefore, it was concluded that the decrease of reactivity with increased chain
      length is probably not a consequence of a lower affinity of the substrate for the
      enzyme. The fact that butyrate ester has the optimum acyl-chain length to be a
      substrate of LPL can be attributed to its chain length being long enough for
      optimum interaction with the active site His-Ser-Asp triad in forming the
      transition state complex; yet it is short enough to provide freedom for optimum
      positioning of the ester bond for transition state complex formation. It is
      likely that, because of the structural features of the enzyme active site, the
      increase of the acyl-chain of the substrate from C4 to C5 initiates the contact
      between the hydrocarbon tail of the acyl-chain and the hydrophobic surface of the
      active site pocket. Such an interaction, although it causes the stabilization of
      the ground state enzyme-substrate complex, also causes a large increase in
      negative activation entropy because of the restricted random motion of the bound
      substrate. The latter effect is also the likely cause for the progressively lower
      reactivity of the enzyme with the increase of acyl-chain length above C4, as seen
      in the LPL-catalyzed lipolysis of monoacid triacylglycerols.

PMID- 8155729
TI  - Slow relaxation process in the main transition of phosphatidylcholines studied
      with heat capacity spectroscopy. I. Multilamellar vesicles.
AB  - Extremely slow relaxation processes have been examined near the main transition
      of multilamellar vesicle samples of dimyristoylphosphatidylcholine (DMPC) and
      dipalmitoylphosphatidylcholine (DPPC) with a heat capacity spectroscopic
      technique. The dynamic heat capacity showed a significant frequency dependence in
      the studied frequency region of 0.5 mHz to 50 mHz. The relaxation observed here
      has been analyzed with the Cole-Cole equation. The mean relaxation times were 120
      s in DMPC, and 260 s in DPPC. The relaxation showed a polydispersive character.
      The parameter beta was around 0.5 in both DMPC and DPPC.

PMID- 8155730
TI  - Apolipoprotein B of oxidized LDL accumulates in the lysosomes of macrophages.
AB  - We have studied the intracellular fate of the apolipoprotein B of copper-oxidized
      LDL in cultured J774 macrophages, using subcellular fractionation and
      immunofluorescence techniques. The oxidized apolipoprotein B, using cell
      fractionation, was located primarily in secondary lysosomes (identified using the
      lysosomal marker-enzyme aryl sulfatase). Light microscopy using antibodies to the
      mannose-6-phosphate receptor, the lysosomal membrane protein lgp 120, and
      oxidized LDL (biotinylated) confirmed that apo B of oxidized LDL did accumulate
      in secondary lysosomes rather than in endosomes. We conclude from these results
      that the oxidized apolipoprotein B of LDL reaches the secondary lysosomes, but is
      not efficiently degraded, leading to intracellular accumulation within this
      compartment. If this occurs in vivo it may influence the physiology of the
      macrophage and their subsequent roles in forming foam cells and the development
      of the fatty streaks of early atherosclerosis.

PMID- 8155731
TI  - Characterization of polyprenyldiphosphate: 4-hydroxybenzoate
      polyprenyltransferase from Escherichia coli.
AB  - Polyprenyldiphosphate: 4-hydroxybenzoate polyprenyltransferase (4-HB
      polyprenyltransferase) is a key enzyme in ubiquinone biosynthesis in E. coli,
      encoded by the gene ubiA. By overexpression of ubiA and isolation of the membrane
      fraction, the enzyme was enriched approx. 3000-fold and characterized. The enzyme
      is membrane-bound and could not be solubilized by hypotonic buffer or detergent
      treatment. The enzymatic activity is optimal at pH 7.8 and depends on the
      presence of magnesium ions. Geranyldiphosphate (GPP), all-trans
      farnesyldiphosphate (FPP) and all-trans-solanesyldiphosphate (SPP) are accepted
      as side chain precursors. The apparent Km values for these substances are are 254
      microM, 22 microM and 31 microM, respectively. No reaction was observed with
      omega-t2-c5-octaprenyldiphosphate, in which five double bounds have cis
      configuration. The reaction is stimulated by 0.01% CHAPS, but strongly inhibited
      by sodiumdeoxycholate, Tween 80 and Triton X-100. The amino acid sequence shows
      striking similarities to 4-HB hexaprenyltransferase from yeast. Sequence
      homologies to other prenyltransferases are discussed.

PMID- 8155732
TI  - Expression of high activity of ornithine decarboxylase and occurrence of unusual
      chromophobic cells in anterior pituitary gland of a novel growth-retarded strain
      of mice, grm/grm.
AB  - Extremely high activity of ornithine decarboxylase (ODC) was detected in the
      pituitary gland of growth-retarded mice, grm/grm at 2 months after birth. The
      elevated enzyme activity gradually decreased to the control level in 14 months
      after birth. In the pituitary gland of the growth-retarded mice, unusual
      chromophobic cells were also present from the early stages after birth. The
      chromophobic cells showed conspicuous proliferations and resulted in a distinct
      hyperplasia of the tissue after 4 months after birth. These findings suggest that
      ODC is correlated to the progressive transformation of pituitary cells into the
      chromophobic cells.

PMID- 8155733
TI  - Angiotensin converting enzyme (kininase II) mRNA production and enzymatic
      activity in human peripheral blood monocytes are induced by GM-CSF but not by
      other cytokines.
AB  - Peripheral blood monocytes (PBM) do not possess angiotensin converting enzyme
      (ACE) activity in the inactive state. However, measurable PBM ACE activity is
      found in patients with certain inflammatory diseases. We have examined the effect
      of cytokines likely to be present during granulomatous inflammation on the
      regulation of ACE mRNA in PBM. The presence of ACE mRNA in human PBM cultured in
      vitro with various cytokines for up to 6 days was analyzed using polymerase chain
      reaction. PBM not exposed to cytokines did not express ACE mRNA, while incubation
      of PBM with recombinant human GM-CSF resulted in high levels of ACE mRNA
      expression after 72 h of cell culture, which persisted through day six. Increased
      ACE mRNA expression occurred concomitantly with phenotypic changes in cell size
      and shape consistent with cell activation. A 5-fold increase in ACE enzymatic
      activity also occurred. Incubation of PBM with all other cytokines tested failed
      to induce ACE mRNA expression. Alveolar macrophages expressed ACE mRNA
      immediately following their isolation, but mRNA expression decreased markedly
      during a 24-h period of incubation and was only partially reversed with exogenous
      GM-CSF. We conclude that GM-CSF enhances ACE mRNA levels in human PBM, but not in
      alveolar macrophages.

PMID- 8155735
TI  - Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine
      deficiency is probably in renal carnitine transport system.
AB  - We investigated the reabsorptional system for carnitine in the kidney to
      elucidate the mechanism of carnitine deficiency in juvenile visceral steatosis
      (jvs) mice. Jvs mice had a higher rate of carnitine excretion at 10 days after
      birth than the controls, in spite of having no pathological acylcarnitine
      excretion in the urine. In an experiment to assay the uptake of carnitine using
      kidney slices, homozygous mutants showed significantly lower rates of Na
      dependent carnitine uptake than controls. Heterozygous mice showed values of
      transport activity intermediate between homozygous mutants and homozygous
      controls. Scatchard plots (transport activity versus transport activity/carnitine
      concentration) revealed that the homozygous mutants had a defect in the high
      affinity site (Km = 58 microM) in the Na-dependent carnitine transport system in
      the kidney. These results indicate that the primary defect of jvs mice is most
      probably related to the system for reabsorption of carnitine in the kidney.

PMID- 8155734
TI  - Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor
      gene expression in aortic smooth muscle cells of spontaneously hypertensive rats.
AB  - To examine the regulation of angiotensin receptors in vascular smooth muscle
      cells, we studied the effects of antihypertensive drugs on angiotensin type 1A
      (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from
      spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay
      and reverse-transcription polymerase chain reaction. An increase in AT1A receptor
      gene expression in ASMCs of SHRs was induced by treatment with an angiotensin
      converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other
      types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta
      blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle
      relaxant (hydralazine). Since all antihypertensive drugs lowered the blood
      pressure of the rats almost equally, our results suggest that AT1A receptor gene
      expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin
      system.

PMID- 8155736
TI  - Myoglobin signal as an NMR tissue thermometer: implication for hyperthermia
      treatment of tumors.
AB  - Measuring local tissue temperature is critical in establishing a rational
      approach for hyperthermia treatment of tumors. We have found that the heme
      signals of myoglobin provide a unique basis for NMR thermometry in vivo. In
      particular the 5-methyl heme signal of MbCN exhibits a sharp, temperature
      dependent resonance that is distinguishable in the tissue spectrum. Its
      calibrated chemical shift can then reflect the local tissue temperature in vivo.

PMID- 8155737
TI  - Differential accumulations of 4,977 bp deletion in mitochondrial DNA of various
      tissues in human ageing.
AB  - Several types of deletions in mitochondrial DNA (mtDNA) have been recently
      identified in various tissues of old humans. In order to determine whether there
      are differences in the incidence and proportion of deleted mtDNAs in different
      tissues during human ageing, we examined the 4,977 bp deletion in mtDNA of
      various tissues from subjects of different ages. Total DNA was extracted from
      each of the biopsied tissues and was serially diluted by two-fold with distilled
      water. A 533 bp DNA fragment was amplified by PCR from total mtDNA using a pair
      of primers L3304-3323 and H3817-3836, and another 524 bp PCR product was
      amplified from 4,977 bp deleted mtDNA by identical conditions using another pair
      of primers L8150-8166 and H13631-13650. The maximum dilution fold of each sample
      that still allowed the ethidium bromide-stained PCR product (533 bp or 524 bp) in
      the agarose gel to be visible under UV light illumination was taken as the
      relative abundance of the mtDNA (wild-type or mutant) in the original sample. By
      this method, we were able to determine the proportion of deleted mtDNA in human
      tissues. We found that the 4,977 bp deletion started to appear in the second and
      third decades of life in human muscle and liver tissues. But the deletion was not
      detectable in the testis until the age of 60 years. Moreover, the proportion of
      deleted mtDNA varied greatly in different tissues. Among the tissues examined,
      muscle was found to harbor higher proportion of deleted mtDNA than the other
      tissues. The average proportion of the 4,977 bp deleted mtDNA of the muscle from
      subjects over 70 years old was approximately 0.06%, and that of the liver and the
      testis was 0.0076% and 0.05%, respectively. These findings suggest that the
      frequency and proportion of the deleted mtDNA in human tissues increase with age
      and that the mtDNA deletions occur more frequently and abundantly in high energy
      demanding tissues during the ageing process of the human.

PMID- 8155738
TI  - Studies on the urinary excretion of thromboxane B2 in Zellweger patients and
      control subjects: evidence for a major role for peroxisomes in the beta-oxidative
      chain-shortening of thromboxane B2.
AB  - In this paper we studied the urinary excretion of thromboxane B2 and its beta
      oxidation product 2,3-dinor-thromboxane B2 in urines from control subjects and
      four Zellweger patients, which lack morphologically distinguishable peroxisomes.
      In the urine of three classical Zellweger patients we found a ratio of 2,3-dinor
      thromboxane B2/thromboxane B2 of 0.35, 0.48 and 0.62 respectively, whereas in
      healthy children and adults values were found of 3.1-10 and 5.5-40 respectively.
      These data strongly suggest that peroxisomes are a major site for beta-oxidation
      of thromboxane B2.

PMID- 8155739
TI  - Automatic sequencing of mitochondrial tRNA genes in patients with mitochondrial
      encephalomyopathy.
AB  - We have investigated nine children with infantile onset of mitochondrial myopathy
      and two adults with myoclonus epilepsy and ragged-red fibers (MERRF) and chronic
      progressive external ophthalmoplegia (CPEO), respectively. These patients lacked
      any of the previously known pathogenic tRNA mutations. Southern blot analysis of
      muscle mtDNA revealed no deletions. The tRNA genes of muscle mtDNA were
      sequenced. Restriction enzyme analysis of PCR fragments was performed to verify
      the presence of the mutations identified by automatic sequencing. Several tRNA
      mutations were found, but they were all homoplasmic. Furthermore, the mutations
      were either present in controls or did not change nucleotides conserved between
      species. This strongly suggests that none of the tRNA mutations identified in the
      11 patients with mitochondrial encephalomyopathy was pathogenic. It can thus be
      concluded that mitochondrial tRNA mutations and mtDNA deletions probably are an
      infrequent cause of mitochondrial disorders in infants. Patients with MERRF and
      CPEO may lack both pathogenic point mutations of tRNA genes and deletions of
      mtDNA.

PMID- 8155740
TI  - Direct detection of radical generation in rat liver nuclei on treatment with
      tumour-promoting hydroperoxides and related compounds.
AB  - EPR spin trapping has been employed to directly detect radical production in
      isolated rat liver nuclei on exposure to a variety of hydroperoxides and related
      compounds which are known, or suspect, tumour promoters. The hydroperoxides, in
      the absence of reducing equivalents, undergo oxidative cleavage, generating
      peroxyl radicals. In the presence of NADPH (and to a lesser extent NADH)
      reductive cleavage of the O-O bond generates alkoxyl radicals. These radicals
      undergo subsequent rearrangements and reactions (dependent on the structure of
      the alkoxyl radical), generating carbon-centred radicals. Acyl peroxides and
      peracids appear to undergo only reductive cleavage of the O-O bond. With peracids
      this cleavage can generate aryl carboxyl (RCO2.) or hydroxyl radicals (HO.); with
      acyl peroxides, aryl carboxyl radicals are formed and, in the case of t-butyl
      peroxybenzoate, alkoxyl radicals (RO.). The radicals detected with each peroxide
      are similar in type to those detected in the rat liver microsomal fraction,
      although the extent of radical production is lower. The subsequent reactions of
      the initially generated radicals are similar to those determined in homogeneous
      chemical systems, suggesting that they are in free solution. Experiments with
      NADPH/NADH, heat denaturation of the nuclei and various inhibitors suggest that
      radical generation is an enzymatic process catalysed by haemoproteins, in
      particular cytochrome P-450, and that NADPH/cytochrome P-450 reductase is
      involved in the reductive cleavage of the O-O bond. The generation of these
      radicals by the rat liver nuclear fraction is potentially highly damaging for the
      cell due to the proximity of the generating source to DNA. Several previous
      studies have shown that some of the radicals detected in this study, such as aryl
      carboxyl and aryl radicals, can damage DNA, via various reactions which result in
      the generation of strand breaks and adducts to DNA bases: these processes are
      suggested to play an important role in the tumour promoting activity of these
      hydroperoxides and related compounds.

PMID- 8155741
TI  - Chromate-mediated free radical generation from cysteine, penicillamine, hydrogen
      peroxide, and lipid hydroperoxides.
AB  - The Cr(VI)-mediated free radical generation from cysteine, penicillamine,
      hydrogen peroxide, and model lipid hydroperoxides was investigated utilizing the
      electron spin resonance (ESR) spin trapping technique. Incubation of Cr(VI) with
      cysteine (Cys) generated cysteinyl radical. Radical yield depended on the
      relative concentrations of Cr(VI) and Cys. The radical generation became
      detectable at a cysteine:Cr(VI) ratio of about 5, reached its highest level at a
      ratio of 30, and declined thereafter. Cr(VI) or Cys alone did not generate a
      detectable amount of free radicals. Similar results were obtained with
      penicillamine. Incubation of Cr(VI), Cys or penicillamine and H2O2 led to
      hydroxyl (.OH) radical generation, which was verified by quantitative competition
      experiments utilizing ethanol. The mechanism for .OH radical generation is
      considered to be a Cr(VI)-mediated Fenton-like reaction. When model lipid
      hydroperoxides such as t-butyl hydroperoxide and cumene hydroperoxide were used
      in place of H2O2, hydroperoxide-derived free radicals were produced. Since
      thiols, such as Cys, exist in cellular systems at relatively high concentrations,
      Cr(VI)-mediated free radical generation in the presence of thiols may participate
      in the mechanisms of Cr(VI)-induced toxicity and carcinogenesis.

PMID- 8155742
TI  - Decline with age of the respiratory chain activity in human skeletal muscle.
AB  - Mitochondrial respiratory systems have been screened in 63 orthopaedic patients
      of age ranging between 17 and 91 years. The results show a statistically
      significant definite decrease with ageing of mitochondrial respiratory activity
      with pyruvate plus malate, succinate and ascorbate plus TMPD. This pattern is
      associated with an equally significant decrease with age of the enzymatic
      activity of complex I, II and IV. No significant decrease with age is, on the
      contrary, observed in the mitochondrial content of cytochromes a+a3, and c+c1.
      Preliminary Western blot analysis indicates an altered polypeptide pattern in
      cytochrome c oxidase. This study provides evidence for a decline with age of
      mitochondrial respiratory activity in human skeletal muscle, affecting complex I,
      II and IV.

PMID- 8155744
TI  - Oncogene overexpression and de novo drug-resistance in human prostate cancer
      cells.
AB  - We have isolated a variant [PC3(R)] of the human prostate PC3 tumor cell line
      which showed resistance to several anticancer drugs. Studies to evaluate the
      mechanisms of resistance to anticancer drugs in the PC3(R) cell line indicated
      that mdr1 was not overexpressed. Studies also indicated that activities of topo I
      and topo II were not different in these cell lines, nor was there any difference
      in the formation of drug-induced KCl-SDS precipitable complexes, indicating that
      topoisomerases were not involved in the development of resistance in PC3(R)
      cells. While the activity of glutathione S-transferase and total glutathione
      levels were also similar in these cell lines, the glutathione peroxidase activity
      in PC3(R) cells was 5-fold lower than in PC3 cells. Furthermore, proto-oncogene
      expression for c-jun, c-myc, and H-ras was significantly higher in resistant
      cells than in sensitive cells, indicating that the amplification of early
      response genes may play a role in the emergence of de novo resistance in PC3(R)
      cells.

PMID- 8155743
TI  - Multinuclear NMR studies of intracellular cations in the prehypertensive rat
      kidney.
AB  - We previously reported a significant derangement of intracellular free calcium
      ion concentration in the isolated perfused kidney of adult spontaneously
      hypertensive rat (SHR) (J. Biol. Chem. 267, 3637-3643, 1992). In order to
      investigate whether an abnormality in intracellular free calcium or another ion
      precedes the development of elevated blood pressure in SHR, we have now compared
      intracellular free Ca2+, Na+ and pH, using 31P, 19F, and triple quantum-filtered
      (TQ) 23Na NMR, in perfused kidneys from prehypertensive young SHR and
      normotensive young Wistar-Kyoto (WKY) rats (5-6 weeks old) which showed no
      significant difference in blood pressure (B.P. = 120 +/- 5 mmHg and 115 +/- 3
      mmHg, for SHR and WKY rats, respectively). Like the adult kidney, no significant
      differences in intracellular ATP concentration or intracellular pH were found
      between young prehypertensive SHR and normotensive WKY rat kidneys. The TQ 23Na
      NMR signal was 47% higher in the SHR kidney, but, due to biological variability
      and measurement errors, this difference could not be shown to be statistically
      significant. However, a significant (40%; P < 0.05) increase was found in O2
      consumption rate, a measure of the Na+/K(+)-ATPase activity, of the young
      prehypertensive SHR kidney in comparison to the age-matched WKY rat kidney (7.25
      +/- 0.75 for SHR vs. 5.17 +/- 0.18 mumol O2/min g for WKY rat, n = 6).
      Furthermore, a highly significant (92%; P < 0.02) increase in intracellular free
      Ca2+ concentration was observed in kidneys from young SHR that had not yet
      developed high blood pressure in comparison to the kidneys from young
      normotensive WKY rats (648 +/- 76 nM vs. 339 +/- 39 nM, n = 4), despite the fact
      that there was no significant difference in blood pressure. Increased
      intracellular free Ca2+ thus appears to be part of a primary defect, in the
      prehypertensive young SHR kidney, which may, by way of increased release of
      arachidonic acid, and subsequent increased production of vasoconstricting
      arachidonic acid metabolites via the cytochrome P450 pathway, induce elevated
      blood pressure in the adult SHR.

PMID- 8155745
TI  - Quantification of L-tryptophan and L-kynurenine by liquid chromatography/electron
      capture negative ion chemical ionization mass spectrometry.
AB  - In a number of infectious and inflammatory diseases, stimulation of the immune
      system can lead to increased accumulation of tryptophan metabolites via induction
      of kynurenine pathway enzymes in extrahepatic tissues. We developed a liquid
      chromatographic/mass spectrometric (LC/MS) method suitable for tracing the
      disposition of 13C isotopomers of L-tryptophan and L-kynurenine in various
      cultured cell, tissue slice, and whole animal model systems used to investigate
      tryptophan flux through the kynurenine pathway. The method employs extractive
      derivatization of the analytes and their 2H internal standards with
      pentafluorobenzyl bromide in order to enhance the negative ion chemical
      ionization (NICI) mass spectrometric response. Normal-phase liquid
      chromatographic separation of derivatized analytes was optimized using a silica
      column with organic solvents, followed by particle beam transfer and NICI-MS.
      Standard curves were linear over the range 1-250 ng per sample. Particle beam and
      mass spectrometric operating parameters were optimized with direct flow
      injections of 1-(methylamino) anthraquinone, which is an ideal test compound for
      the evaluation of LC/NICI-MS. The developed method was used to quantify the
      conversion of (13C6)L-tryptophan to (13C6)L-kynurenine by human monocytes (THP-1)
      stimulated with interferon-gamma, lung and brain tissue slices obtained from
      gerbils immune-stimulated with pokeweed mitogen. The effect of whole body immune
      stimulation on the plasma levels of endogenous L-kynurenine in mice stimulated
      with interferon-gamma was also quantified.

PMID- 8155746
TI  - Quantitative determination of F6-1,25(OH)2 vitamin D3 in human serum by gas
      chromatography/mass spectrometry with high-resolution selected ion monitoring.
AB  - A highly sensitive and specific gas chromatographic/mass spectrometric method was
      developed for the determination of very low levels of F6-1,25(OH)2 vitamin D3, a
      new fluoro analogue of vitamin D3, to facilitate investigation of its
      pharmacokinetics in man. Deuterium-labelled F6-1,25(OH)2 vitamin D3 was employed
      as an internal standard for quantification. The method involves extraction from
      serum samples, separation by a cartridge column system followed by straight-phase
      high-performance liquid chromatography, O-trimethylsilylation, and analysis by
      gas chromatography/mass spectrometry using high-resolution selected ion
      monitoring. With a quantification limit of 2 pg ml-1 and a requirement for 2 ml
      of serum, the assay method has sufficient sensitivity, selectivity and precision
      for the analysis of very low concentrations of the drug.

PMID- 8155747
TI  - Use of electrospray ionization mass spectrometry to probe antisense peptide
      interactions.
AB  - Electrospray ionization mass spectrometry with a magnetic sector instrument has
      been used to test for non-covalent interactions between human angiotensin II
      (M(r) 1046) and eight synthetic octapeptides that are considered complementary
      peptides (encoded by DNA sequences complementary to the DNA sequence that codes
      for human angiotensin II) or analogues of these antisense peptides. The relative
      abundance of the doubly charged heterodimer complex broadly correlates to the
      trend observed with solution-phase studies such as 1H nuclear magnetic resonance.
      Dissociation constants for the reaction in solution are in the high micromolar
      range. Electrospray ionization can potentially be a sensitive method for rapidly
      screening weak molecular interactions. Further work is necessary to study the
      possible gas-phase contributions to the observed binding interactions indicated
      in the mass spectrometry data.

PMID- 8155748
TI  - [Change-over in the management of "Enfermedades Infecciosas y Microbiologia
      Clinica"].

PMID- 8155749
TI  - [Current use of penicillin in community-acquired pneumococcal pneumonias].
AB  - BACKGROUND: A retrospective study was performed to know the clinical and
      microbiologic aspects of community-acquired pneumococcal pneumonia in adult
      patients admitted to a general hospital from 1990-1992. METHODS AND RESULTS: The
      medical records of 55 patients, aged 20-86 years (man age: 58 year) were
      reviewed. Streptococcus pneumoniae was isolated from blood in 45 cases (81.8%),
      transparietal lung puncture in 5 (9.1%), pleural fluid 3 (5.5%) and protected
      specimen brushing (> 1,000 UFC/ml) in 2 (3.6%) Most isolated (80%) were sensitive
      to penicillin (CIM < 0.1 microgram/ml); intermediate (CIM > or = 0.1
      microgram/ml) 9 (16.4%) and resistant (> 1 microgram/ml) 2 (3.6%). Underlying
      diseases were present in 39 (70.9%) cases. All patients received empiric
      treatment with one or more antibiotics effective against Streptococcus
      pneumoniae. Only in 2 of the 9 cases treated with erythromycin the microorganism
      was resistant to this drug. Eleven patients died (20%), 5 died before to the
      fifth day of admission. Mortality was influenced by involvement of 2 or more
      lobes and immunosuppression (p < 0.05). CONCLUSIONS: This study suggests that 80%
      of the community-acquired pneumococcal pneumonia in a population with a high
      prevalence rate of disease requiring hospital admission are very sensitive in
      vitro to penicillin in contrast with its seldom clinical use in the authors
      environment. No microorganism presented with CIM above 2 micrograms/ml. Mortality
      was not due to inadequate therapy but rather to the severity of the underlying
      disease.

PMID- 8155750
TI  - [Clinical and etiological features of community-acquired pneumonia in the
      elderly].
AB  - BACKGROUND: The aim of the present study was to know the clinical and etiologic
      features of community-acquired pneumonia (CAP) in elderly patients requiring
      hospital admission. METHODS: A prospective study of 36 consecutive patients aged
      over 70 years, admitted to a general hospital was performed. Standard analytical
      determinations, blood cultures, and serologic studies were performed in all
      patients using invasive techniques: aspirative transthoracic puncture (ATP) with
      ultrafine needle in 35 (97%) cases, and telescopic catheter (TC) in 1 case.
      RESULTS: The mean age was 79 years (range: 71-90). Twenty-two patients had
      received antibiotic treatment prior to admission (61%) and 17 (47%) presented
      chronic debilitating diseases. The clinical characteristics of CAP were "typical"
      with acute presentation in most. Fifteen cases (42%) were etiologically diagnosed
      and the most frequently isolated agents were Streptococcus pneumoniae (22%) and
      Haemophilus influenzae (8%). Empiric treatment was changed on the basis of
      isolations in 7 cases (19%). Eight patients died (22%). CONCLUSIONS: According to
      our results community-acquired pneumonia in the population studied: 1) generally
      showed an acute presentation with "typical" characteristics, carrying a high
      mortality rate (22%), 2) is of bacterial etiology, with S. pneumoniae and H.
      influenzae being the most frequently isolated microorganisms, 3) the use of ATP
      in community-acquired pneumonia offers a high diagnostic effectiveness, good
      tolerance and low risk of complications.

PMID- 8155751
TI  - [Varicella pneumonia in adults infected by HIV-1. Presentation of 2 cases].
AB  - BACKGROUND: Infection by the varicella-zoster virus (VZV) is frequent in patients
      infected by the HIV-1. Nonetheless, visceral involvement in addition to that of
      pneumonia is rare, despite the important immune dysfunction found among these
      patients. METHODS: Varicella pneumonia was diagnosed in 2 patients with HIV-1
      infection who presented cough with high fever and a characteristic rash in
      addition to respiratory failure and a micronodular pattern on chest radiography.
      The medical literature is reviewed (MEDLINE). RESULTS: An excellent clinical
      response was achieved with endovenous acyclovir treatment. CONCLUSIONS: The
      authors underline how rare is varicella pneumonia in patients with HIV-1
      infection. The appearance of a pustulous vesicular rash in the context of a
      febrile episode leads to suspicion of this diagnosis. The treatment of choice is
      endovenous acyclovir (5 mg/kg/8 h). Varicella pneumonia has also been described
      in children with HIV-1 infection. The possible increase in patients with
      varicella pneumonia with be assessed, due to the immunosuppressive state of these
      patients. Patients not having been in contact with the varicella-zoster virus are
      particularly susceptible to presenting primoinfection by this virus.

PMID- 8155752
TI  - [Bacteremia caused by Campylobacter jeikeium in 2 AIDS patients without
      neutropenia].
AB  - BACKGROUND: Bacteremia by Corynebacterium jeikeium is generally described in
      patients with a bone marrow transplantation and/or neutropenia. In 1991, the
      first case of bacteremia by C. jeikeium was described in a patient with AIDS and
      neutropenia. The aim of this study was to describe 2 cases of bacteremia by C.
      jeikeium in patients with AIDS without neutropenia. To the authors' knowledge,
      this presentation has not been described previously. METHODS: The bacteremia
      episode was related with a central venous catheter in both patients. The first
      patient was diagnosed of tuberculous lymphadenitis and cerebral toxoplasmosis and
      the second patient of disseminated tuberculosis. Both receive specific treatment
      for these diseases. Zidovudine was not administered. The bacteremia resolved in
      both cases after withdrawal of the catheter and antibiotic treatment with
      vancomycin. CONCLUSIONS: Bacteremia by Corynebacterium jeikeium should be
      considered in the differential diagnosis of febrile patients with AIDS and
      vascular catheters, even if granulocytopenia is not present. The isolation of C.
      jeikeium from blood in AIDS patients, particularly neutropenic patients, should
      be carefully evaluated by microbiologists and clinicians prior to discard it as a
      "contaminant".

PMID- 8155753
TI  - [Bacteremia caused by Haemophilus influenzae with special reference to its
      relation to HIV infection].
AB  - BACKGROUND: The association between infection by Haemophilus influenzae and
      infection by the human immunodeficiency virus (HIV) has been clearly
      demonstrated. However, some characteristics of this association still remain
      poorly defined. METHODS: The medical records of all adult patients admitted to a
      general hospital over a period of four years with blood cultures positive for
      Haemophilus influenzae were reviewed. Patients were grouped according to whether
      HIV infection or no evidence of HIV infection existed. Clinical and epidemiologic
      data were collected and compared. The main features of data corresponding to
      seropositive patients are reported. RESULTS: Of a total of 29 cases of bacteremia
      by Haemophilus influenzae, 19 were diagnosed in adults: 5 in patients with HIV
      infection and 14 in patients without HIV infection. Over the following 18 months
      one additional case was reported. The incidence (calculated in cases per 100,000
      people/year) was 1.9 in the general population, 1.5 in adults, 70 in adults with
      HIV infection and 360 in AIDS patients. All the cases diagnosed in adults below
      the age of 30 years were reported in HIV carriers. Five of the 16 (31%) H.
      influenzae strains tested were resistant to ampicillin, with a significant
      difference being found between those isolated from HIV positive patients (4/5)
      and from HIV negative patients (1/11). No patient with HIV infection died during
      the episode. But five of the HIV negative adults died. CONCLUSIONS: HIV infection
      seems to be frequent risk factor for bacteremia by Haemophilus influenzae. It
      should always be considered on diagnosis in adults under the age of 30. Likewise,
      the high probability of resistance to ampicillin should also be taken into
      account for the empiric treatment.

PMID- 8155754
TI  - [Slowly developing cavitated pneumonia in a patient with HIV infection].

PMID- 8155755
TI  - [Pneumonia in patients undergoing heart surgery].
AB  - OBJECTIVE: We performed a follow-up study of 104 consecutive patients who
      underwent cardiac surgery to ascertain the following: 1) the incidence of
      nosocomial pneumonia (NP) in this patient population; 2) the differences in the
      incidence of NP between patients who underwent coronary artery bypass grafting
      (CABG) vs. valvular replacement (VR), and 3) the identification of risk factors
      which predispose patients to the development of NP. RESULTS: The study included
      104 patients of which 49 underwent VR, 43 CABG and 12 who had both procedures
      performed simultaneously. Six of the 104 patients developed NP (5.7%). Five of
      these patients had undergone VR where as opposed to only one in the CABG group.
      Pulmonary hypertension preoperatively was a risk factor for the development of
      NP. Of the 49 patients in the VR group, 46 had pulmonary artery pressures (PAP)
      recorded, and from their 23 (50%) had pulmonary hypertension. However, 4 of the 5
      (80%) patients who developed NP had elevated PAP. The mortality among patients
      with NP was high. Sixty six percent of patients (4/6) with NP died in comparison
      to the 10 deaths (10.2%) among 92 patients without NP (p = 0.002). CONCLUSIONS: A
      trend in the development of NP was observed in patients who underwent valve
      replacement as opposed to CABG. Because of the small number of patients who
      developed pneumonia in the study population statistical significance cannot be
      reached. Pulmonary hypertension in the post operative period is a risk factor for
      the development of NP. Mortality among patients who develop NP is significantly
      high (p = 0.002).

PMID- 8155756
TI  - [Practical approach to bacteremia].

PMID- 8155757
TI  - [Endocarditis caused by Streptococcus gordonii].

PMID- 8155758
TI  - [Prolonged fever as an unusual form of presentation of a Mycoplasma pneumoniae
      infection].

PMID- 8155759
TI  - [Pulmonary mucormycosis with few symptoms in a patient with lung cancer].

PMID- 8155760
TI  - ["Detection of respiratory syncytial virus antigen in respiratory secretions"].

PMID- 8155761
TI  - [Arthritis caused by Neisseria meningitidis].

PMID- 8155762
TI  - [Splenic abscess caused by Salmonella enteritidis. Successful percutaneous
      drainage in 2 patients].

PMID- 8155763
TI  - [Hyperkeratotic dermatitis in a patient with HIV infection].

PMID- 8155765
TI  - Gene therapy for cancer.

PMID- 8155764
TI  - [Bacteremia caused by anaerobes: analysis of 131 episodes].
AB  - BACKGROUND: Despite the efficacy of modern antimicrobials bacteremia by anaerobes
      (AB) continues to present a high mortality rate. The aim of this study was to
      determine the relative frequency and clinical significance of isolations of
      anaerobic bacteria in blood cultures and to know the prognostic factors of AB.
      METHODS: From total of 231 patients observed over a period of six and a half
      years in the Fundacion Jimenez Diaz, 131 episodes of AB were retrospectively
      analyzed with special attention being given to microbiologic, epidemiologic and
      clinical factors. RESULTS: The relative frequency of AB was 7.5%. Clinical
      significance was found in 86 out of the 131 episodes (66%). The isolation of
      Bacteroides spp. was clinically significant in 89% while Clostridium spp. was so
      only in 33% (p < 0.001). Mortality related with AB was 32%. The following factors
      were considered related to bad prognosis statistical analysis (p < 0.05):
      admission to medical areas, rapid and finally fatal underlying disease, presence
      of septic shock, renal failure, inappropriate antimicrobial treatment and the
      absence of drainage for the septic foci. CONCLUSIONS: Anaerobic bacteremia
      remains an important cause of bacteremia and carries a high mortality rate. Two
      thirds of the episodes of anaerobic bacteremia are deemed to be clinically
      significant. Correct antimicrobian treatment and surgical drainage of any septic
      foci significantly improves prognosis.

PMID- 8155766
TI  - Gene transfer in regenerating muscle.
AB  - We have compared the efficiency of direct gene transfer in normal and
      regenerating rat skeletal muscle. Muscle necrosis and regeneration was induced by
      intramuscular injection of bupivacaine in the soleus muscle of adult rats.
      Plasmids containing beta-galactosidase (beta-gal) or chloramphenicol
      acetyltransferase (CAT) genes driven by viral promoters were injected 3 days
      after bupivacaine treatment into the regenerating and the contralateral uninjured
      muscles. Expression of CAT activity was > 80-fold higher in regenerating compared
      to control muscles at 7 days post-transfection, but decreased at 30 and 60 days.
      Southern blot analysis showed that the predominant form of CAT DNA was episomal
      in transfected muscles; however, CAT activity measurements performed on the same
      transfected muscles showed no precise correlation between enzymatic activity and
      amount of plasmid DNA. Expression of beta-gal was detected in numerous
      regenerating fibers of the injured soleus muscles at 7 days post-transfection; in
      contrast, only rare positive fibers were found in control muscles. Focal
      infiltrates of mononuclear cells, which surround and invade selectively beta-gal
      positive fiber segments, were observed at 30 days post-transfection, suggesting
      that immune mechanisms are implicated in the progressive loss of transgenes with
      time. The finding that regenerating muscle fibers display a higher efficiency of
      transfection may be relevant to gene therapy of Duchenne muscular dystrophy,
      because regenerating fibers are numerous in the early stages of the disease.

PMID- 8155767
TI  - Improved methods of retroviral vector transduction and production for gene
      therapy.
AB  - To facilitate clinical applications of retroviral-mediated human gene transfer,
      retroviral vectors must be of high titer and free of detectable replication
      competent retroviruses. The purpose of this study was to optimize methods of
      retroviral vector production and transduction. Studies were conducted using 22
      retroviral vector producer cell lines. Inactivation of retroviral vectors was
      greater at 37 degrees C than at 32 degrees C. A 5- to 15-fold increase of vectors
      was produced at 32 degrees C compared to 37 degrees C; the vector increase at 34
      degrees C was intermediate. For example, PA317/G1Na.40 grew to a titer of 1.8 x
      10(7) cfu/ml at 32 degrees C, compared to 5.0 x 10(5) cfu/ml at 37 degrees C. The
      production of retroviral vectors was scalable achieving similar results in
      flasks, roller bottles, or a CellCube Bioreactor. Retroviral vectors were
      concentrated 15-24 times with vector recovery ranging from 91 to 96% in a
      Pellicon tangential flow filtration system. Retroviral supernatants were
      successfully lyophilized. The combination of glucose or sorbitol with gelatin
      resulted in recovery rates of 64-83%. In studies on transduction by retroviral
      vectors, centrifugation of vector supernatants onto target cells significantly
      increased transduction efficiency as measured by vector titration for G418
      resistance, fluorescence-activated cell sorting (FACS), and polymerase chain
      reaction (PCR) analyses. The combination of the above methods has significantly
      increased the growth and transduction by this vector system.

PMID- 8155768
TI  - Surfactant protein A-directed toxin gene kills lung cancer cells in vitro.
AB  - Human surfactant protein A (SPA) expression is considered a marker of respiratory
      epithelial differentiation. Non-small cell lung cancers (NSCLC) are respiratory
      epithelial derivatives, and it was previously shown that a minority of these
      cancers expressed SPA, presumably a consequence of their respiratory epithelial
      origin. In the studies reported here, SPA-I gene transcriptional regulatory
      sequences were localized to a 2.75-kb genomic 5'-flanking region fragment
      obtained by screening a human genomic library. The 2.75-kb fragment was used to
      direct a luciferase coding sequence transcriptionally within a plasmid construct.
      In plasmid transduction experiments, the SPA-directed luciferase plasmid produced
      significant luciferase activity in the SPA-expressing NSCLC cell line, H441, but
      only background levels in the non-SPA-expressing A549 cells. Because Northern
      blot analysis of resected NSCLC showed that the majority expressed SPA, an SPA
      transcriptional targeting strategy was investigated using chimeric toxin genes
      comprising the coding sequence for herpes simplex virus thymidine kinase (HSV-TK)
      under transcriptional control of SPA or SV40 regulatory sequences. As expected,
      transduction of the constitutive, SV40-directed plasmid followed by ganciclovir
      treatment reduced numbers of both the A549 and H441 cells. In contrast, the SPA
      directed plasmid reduced only the SPA-expressing H441 cells and had no
      significant effect on the A549 cells. The results of these in vivo experiments
      suggest the concept of transcriptionally directing toxin genes with SPA can
      produce targeted toxicity in NSCLC.

PMID- 8155770
TI  - Heredity: science and society on the possibilities and limits of genetic testing
      and gene therapy. Report issued by a Committee of the Health Council of The
      Netherlands.

PMID- 8155769
TI  - Lung gene therapy: in vivo adenovirus-mediated gene transfer to rhesus monkey
      airway epithelium.
AB  - Somatic gene therapy of lung disorders such as cystic fibrosis (CF) aims at
      introducing the therapeutic gene into respiratory epithelium. We have tested the
      ability of recombinant human adenovirus to infect rhesus monkey airway epithelium
      in vivo. Application of adenovirus harboring the lacZ marker gene to the airway
      surface resulted in large patches of lacZ-positive cells in the trachea, bronchi,
      and bronchioles, 6 days after virus exposure, indicating a successful transfer of
      the lacZ gene to respiratory epithelium. Microscopic analysis showed that basal,
      mucous goblet, and ciliated cells were lacZ positive. In addition, gene transfer
      to the submucosal glands was observed. Pathological examination of the organs
      revealed no virus-mediated toxic effects to the lungs and other organs. Using
      polymerase chain reaction (PCR) analysis we found no spread of the virus to blood
      or any organ tested. These results indicate the potential use and safety of
      adenoviruses as a tool in human gene therapy procedures aimed at pulmonary
      diseases.

PMID- 8155771
TI  - Gene therapy of cancer: a pilot study of IL-4-gene-modified fibroblasts admixed
      with autologous tumor to elicit an immune response.

PMID- 8155772
TI  - Immunotherapy for cancer by direct gene transfer into tumors.

PMID- 8155773
TI  - A molecular genetic intervention for AIDS--effects of a transdominant negative
      form of Rev.

PMID- 8155774
TI  - [An emerging enteropathogen?].

PMID- 8155775
TI  - [Occupational accidents in Municipio Maracaibo, Estado Zulia, Venezuela, 1979
      1990. Determination of the frequency and risk factors which play a role in their
      production].
AB  - During the period of 1979-1990 job-related injuries were studied in Maracaibo,
      Zulia state, in order to analyze frequencies and causes. This information was
      obtained from annual reports on job-related injuries Form Number 15-411 of the
      Venezuelan Institute of Social Security (IVSS) which has been implemented
      nationally since 1982. Accidents that caused loss of man-hours were considered;
      variables considered were: age, risk category, day of the week, work shift,
      month, type of accident, agent, type of lesion, mechanical cause, body part
      affected and type of the activity in which the company is involved. The results
      were expressed as absolute values (mean +/- SE) and relative values. The mean
      accidents/year was 1651 +/- 177.97, most of them occurring in the age groups of
      20-29 years (368.8) and 30-39 years (359.8). The triannual mean rate was higher
      for the group of the non-serious accidents (50%). Tuesday was the day of higher
      accidental incidence (22%) in addition to the morning shift between 9 and 11
      hours (55%). Manufacturing was the economic activity most affected (43%). The
      most common causative agents were materials, substances and radiations (35%). The
      use of defective tools were the most frequent causes of mechanical accidents
      (31%). Upper limbs (46%) and between the type of lesion contusions or/and bruises
      (53%). It was concluded that, although the number of workers and accidents slowly
      diminished, the accidents rate slightly increased.

PMID- 8155776
TI  - [Venezuelan equine encephalitis. Determination of antibodies in the human
      population of Municipio Mirand, Estado Zulia, Venezuela].
AB  - With the purpose of determining antibodies prevalence against Venezuelan Equine
      Encephalitis Virus in the population of Puertos de Altagracia and Sabaneta de
      Palmas of Miranda county, Zulia State, Venezuela, 199 subjects were studied: 57
      from Puertos de Altagracia and 142 from Sabaneta de Palmas. They were classified
      in older (42.78%) and younger (57.2%) than 15 years. The blood specimens were
      processed for Hemagglutination Inhibition Test using EEV antigen Goajira strain
      at pH 6.5. We found that all 57 specimens from Puertos de Altagracia were
      negative, whereas of 142 specimens from Sabaneta de Palmas 17 were positive
      (11.97%). Of these, one was from a subject less than 15 years-old (5.85%) and 16
      from individuals more than 15 years-old (94.15%). Positive titers were higher
      than 1:160 in 80% of cases. Being Sabaneta de Palmas one of the most affected
      areas in the 1962 epidemic in the Miranda county and keeping the affected ones
      high positivity with elevated titers, we conclude that this population could
      represent an enzootic zone similar to Paez county where a similar situation, of
      high positivity and elevated titers, many years after the last epidemic occurred
      in that area, has been described.

PMID- 8155777
TI  - [Antiphospholipid antibodies. Review].
AB  - The antiphospholipid antibodies (APA), are immunoglobulins directed against
      anionic phospholipids that adopt a hexagonal configuration after incubation at 37
      degrees C. They are usually IgG, IgM, IgA or a combination of them. Initially
      these antibodies were designated as "lupus anticoagulant", because they were
      found in patients with systemic lupus erythematosus, and because they prolong
      coagulation tests that need phospholipids in the system. The APA antibodies can
      be found associated with a variety of diseases, immunological, infectious,
      malignant disorders etc. They can also be drug related, can be found during
      pregnancy and even in non pregnant normal persons. The main clinical
      manifestations are thrombosis, thrombocytopenia and recurrent fetal losses. The
      diagnosis of APA is usually made, in the absence of antibodies against clotting
      factors, when a prolonged partial thromboplastin time can not be corrected with
      normal plasma. Prothrombin time, plasma recalcification time or the diluted
      Russell viper venom clotting time, are also used for the diagnosis. The
      antibodies and the specific phospholipid or phospholipids involved are usually
      demonstrated by enzymatic methods (ELISA). Depending on the clinical symptoms,
      the presence of APA can go without treatment or need anticoagulant or
      immunosuppressive therapy. Human endovenous immunoglobulin and plasmapheresis
      have also been used, especially during pregnancy.

PMID- 8155778
TI  - [Viral transcription trans-activators].
AB  - The structure and functional peculiarities of a wide range of viral
      transcriptional transactivators have been considered. Analysis of literature
      data, concerning with the principles of functioning has made it possible to
      divide the viral transcriptional transactivators into three major groups:
      transcriptional transactivators of large DNA-containing viruses (Herpes simplex
      virus, Epstein-Barr virus, cytomegalovirus); transactivators of small DNA
      containing viruses (papilloma viruses, papovaviruses, geminiviruses,
      parvoviruses) and viral coactivators. The latter group was identified in
      different DNA-containing viruses (Herpes simplex viruses, papilloma viruses,
      human T-leucosis virus, hepatitis B virus and adenoviruses). The conjecture about
      specific function of metal-binding motifs in activator domains of certain
      transcriptional activators is discussed. The functional features of human
      immunodeficiency virus TAT transactivator was considered separately by virtue of
      its RNA-binding activity.

PMID- 8155779
TI  - [The effect of alpha-tocopherol over a wide range of concentrations (10(-2)-10(
      17) M) on protein kinase C activity. Connection with proliferation and tumor
      growth].
AB  - The effect of the natural antioxidant alpha-tocopherol (alpha-TL) on protein
      kinase C (PK-C) from rabbit heart has been studied. alpha-TL inhibits the PK-C
      activity; the concentration dependence curve has two maxima-at (10(-4)-10(-6) M)
      and at (10(-11)-10(-15) M). There is a "zone of silence" between these two
      regions. The shift of the first maximum towards higher alpha-TL concentrations (5
      x 10(-3) M) and the decrease in the values of the both inhibition maxima (from 80
      90% to 40-60%) was observed for the PK-C preactivated by 12-O-tetradecanoyl
      phorbol-13-acetate. The putative role of alpha-TL and lipid hydroperoxides in the
      regulation of proliferation of normal and tumour cells is discussed.

PMID- 8155781
TI  - [Interconnection of poly-ADP-ribosylation of histones and NAD level in rat liver
      during repair of induced DNA damage].
AB  - The changes in the DNA single strands induced by MNU and the levels of
      poly(ADP)ribosylation of the histone fractions have been studied under conditions
      of increased NAD content in rat liver during the recovery incubation of tissue in
      Hank's solution at 37 degrees C. In the presence of high (in the physiological
      range) NAD concentrations the DNA repair was more active in comparison with the
      control. This process was accompanied by activation of poly(ADP)ribosylation of
      predominantly core histone fractions.

PMID- 8155782
TI  - [A universal method of purifying genetically engineered human somatotropin and
      its mutants using metallochelating agent affinity chromatography].
AB  - A novel scheme for human recombinant somatotropin and its mutant forms isolation
      which includes ion-exchange and metal chelate affinity chromatography has been
      developed. A change in the chromatographic behaviour of the isolated proteins
      depending on the amino acid substitutions has been demonstrated.

PMID- 8155783
TI  - [A calcium channel in the rat liver inner mitochondrial membrane. Effective
      diameter and selectivity under various conditions].
AB  - The pore with an effective diameter of 6.0 A is a Ca(2+)-channel of the inner
      mitochondrial membrane. Transport of nonelectrolytes through the pore is
      inhibited by ruthenium red, a specific Ca2+ transport inhibitor, and by
      polyanions which bind to the positively charged regions in the pore localized on
      the outer side of the inner mitochondrial membrane. The selectivity of Ca2+ ion
      transport into intact mitochondria is due to the binding of Ca2+ ions by the
      glycoprotein at the mouth of the pore as well as to electrostatic interactions of
      monovalent cations (electrostatic repulsion) and Cl- ions (strong binding) with
      the positively charged region of the ion-selective filter of the pore. Under
      normal conditions SCN- and NO3- ions are transferred through the pore at a high
      rate. Removal of Mg2+ ions and the rise in pH diminish the electrostatic
      repulsion of the monovalent cations and Cl- ions from the positively charged
      region of the pore. Depending on conditions, the pore can function as a
      monovalent ion transport system or as a mechanism of Cl- ion transfer through the
      inner mitochondrial membrane.

PMID- 8155784
TI  - [Isolation, purification, and comparative study of the properties of adenosine
      deaminase from five regions of the cattle brain].
AB  - Adenosine deaminase from the white and gray matter of the large hemispheres,
      cerebellum, medulla oblongata and pituitary anterior lobe has been isolated and
      purified. The pH optimum, Km, molecular mass, yield and specific activities for
      all the enzyme preparations have been determined. Gel filtration and
      electrophoresis data point to the heterogeneity of the enzyme. The lack of
      effects of SH-reagents suggests the absence of an essential SH-group. Among five
      bivalent metal ions, only Cu2+ irreversibly inhibited the enzyme activity in all
      the preparations.

PMID- 8155785
TI  - [Stability of isoenzyme C of the collagenolytic protease from the crab
      Paralithodes camtschatica].
AB  - The stability of the isozyme C of the collagenolytic protease of the king crab
      (Paralithodes camtschatica) has been studied. It has been shown that protease C
      is stable at mild alkaline conditions; marked inactivation is observed only at
      temperatures above 40 degrees C. Under these conditions the enzyme
      thermoinactivation is a monomolecular process. CaCl2 and NaCl have no effect on
      the thermoinactivation process. At pH < 6 the enzyme is rapidly and irreversibly
      inactivated, presumably due to the autolytic cleavage. At acidic conditions the
      enzyme is strongly stabilized in the presence of CaCl2, this effect being
      critically dependent on the salt concentration. A stabilizing effect is also
      observed by an increase in the protease C concentration. The enzyme is the most
      labile in strongly alkaline condition; the process its inactivation at pH 11.25
      is not dependent on the enzyme concentration. The protease C retains its activity
      in the presence of detergents but is effectively inhibited by guanidine chloride.

PMID- 8155786
TI  - [Prostaglandin D2-synthase from cattle brain: purification and physico-chemical
      properties].
AB  - Prostaglandin D2-synthase has been purified from bovine brain for the first time
      and characterized. The enzyme has a molecular mass of 21 kDa and a pH optimum at
      9.0 and is activated by dithiothreitol. The presence in the enzyme molecule of
      carbohydrates and lipids has been established and a preliminary conclusion made
      about the qualitative composition of the lipids. The ability of the enzyme to
      form aggregates under the influence of the detergent has been demonstrated. The
      role of the lipid component in the preservation of the enzyme monomeric structure
      as well as the possible mechanisms of action of the above inhibitors and
      activators are discussed.

PMID- 8155788
TI  - [Heterologous expression of functionally active human cytochrome P-450s.
      Cytochrome P-450IIIA4 catalyzes the biotransformation of the anabolic steroid
      hormone methandrostenolone].
AB  - The expression of the cytochrome P450IIIA4 gene in the Saccharomyces cerevisiae
      yeast using the shuttle vector pYeDP1-8/2 has been carried out. The microsomal
      fraction isolated from the transformed yeast cells was used for biotransformation
      of the anabolic steroid hormone-methandrostenolone (MA). The microsomal oxidation
      products were analyzed by HPLC and two-dimensional TLC. It was shown that
      microsomes of the yeasts expressing human cytochrome P450IIIA4 catalyze the MA
      conversion into its 6 beta-hydroxy derivative. An identical product is formed via
      a reaction catalyzed by human liver microsomes. The use of the heterological
      system of cytochrome P450IIIA4 expression has made it possible to establish its
      role in MA metabolism. The experimental system simulates the first phase of the
      drug biotransformation in liver cells.

PMID- 8155787
TI  - [An anionic polysaccharide from the cell wall of Actinoplanes brasiliensis INA
      3802].
AB  - The cell wall of Actinoplanes brasiliensis INA 3802 contains a polysaccharide
      which has an unusual structure. The peculiar structure of the polymer has been
      established by a nondestructive procedure which included 1H- and 13C-NMR
      spectroscopy. The polysaccharide consists of six tetrasaccharide links having the
      following composition -->6(alpha-D-Glc rho-(1-->4)-beta-D-Clc rho 2,3NAcA-(1-->4)
      alpha-D-Clc rho 2,3NAc-(1-->4)-beta- D-Man rho 2,3NAcA-(1-->. No structurally
      identical polymer of the procaryotic cell wall has so far been reported.

PMID- 8155789
TI  - [Biosynthesis and secretion of ceruloplasmin by rat mammary cells during
      lactation].
AB  - Some peculiarities of rat milk ceruloplasmin (CP) biosynthesis have been
      analysed. Electrophoretic and immunoelectrophoretic data suggest that rat milk
      contains up to 20 mg/100 ml of CP. Rat milk CP is represented by a single
      molecular form whose molecular mass, enzymatic activity and antigenic properties
      are fully identical with those of serumal CP. According to the dot hybridization
      date, the CP-mRNA content in rat mammary cells is about ten times as low as that
      in adult rat liver. Analysis of polyribosomal RNA by blot hybridization of RNA
      cDNA revealed that rat mammary CP-mRNA is represented by a single molecular form,
      3.5 kb in length, whose molecular mass is identical with that of the predominant
      CP-mRNA of rat liver. The dynamics of secretion of the de novo synthesized CP
      into rat milk indicates that the CP synthesis and secretion occur independently
      of the serumal CP. In vitro and in vivo pulse labelling studies demonstrated that
      rat milk CP is synthesized and secreted by rat mammary cells.

PMID- 8155790
TI  - [The possibility of using carbon enterosorbents for normalizing cholesterol
      metabolism].
AB  - The kinetics of bile acids (BA) and cholesterol adsorption from biological fluids
      (bile) and reference solutions on carbon SCN were compared with conventional
      medical carbon with the view of elucidating the role of adsorption in improving
      cholesterol metabolism. It was found that the adsorptive capacity of carbon
      adsorbents is determined, primarily, by their porous structure as well by the
      chemical properties of the adsorbing surface. The enterosorbents were tested both
      in experimental animals and in clinical trials and are now successfully employed
      for preventing and treating atherosclerosis as well as for normalizing lipid
      metabolism. A procedure for surgical treatment combined with adsorptive
      detoxication (enterosorption) for patients with obstructive jaundice has been
      developed.

PMID- 8155780
TI  - [Conserved and variable segments of amino acid sequences in alpha-subunits of
      nicotinic acetylcholine receptors and alpha-bungarotoxin-binding proteins].
AB  - A comparative study has been carried out of homologous amino acid sequences of
      alpha-subunits of acetylcholine receptors (AChR) and related proteins classified
      into three groups: (i) alpha-bungarotoxin-binding alpha-subunits of nicotine AChR
      from vertebrate muscles and electrical organ of the skate; (ii) alpha
      bungarotoxin-binding alpha-subunits of neuronal AChR from chicken and rat brain
      and (iii) alpha-bungarotoxin-binding alpha-subunit of chicken brain proteins. The
      experimental results were plotted as intergroup variability profiles obtained by
      comparison of all the sequences within one group with each of the sequences in
      the other group. All of the local variability profiles appeared to be similar and
      contained both highly conservative and highly variable sites. To the former one
      may relate the transmembrane segments M1, M3 and, particularly, M2 as well as the
      81-100 domain comprising several links pertaining to the ligand-binding domain in
      AChR. Domains 153-171 and 177-197 comprising most of the identified links
      involved in the binding of low molecular weight agonists and of alpha
      bungarotoxin appeared to be highly variable ones.

PMID- 8155791
TI  - [Stimulation of respiration in liver mitochondria by glucose in the absence of
      hexokinase activity. The effect of saccharose and several inhibitors of oxidative
      phosphorylation].
AB  - The effect of glucose on rat liver mitochondrial respiration after elimination of
      possible phosphorylation by mitochondrial hexokinase has been studied. It has
      been found that during isolation of mitochondria without washing and their
      subsequent washing with KCl-media glucose stimulates state 3 respiration but has
      no effect on the rate of state 4 respiration or on the uncoupler (2.4
      dinitrophenol)-mediated respiration. The half-maximum effect is observed at the
      glucose concentration of about 2.4 mM. Washing of mitochondria with KCl or their
      isolation in a sucrose-containing medium without washing eliminates the
      stimulating effect of glucose. The sucrose present in the incubation medium
      suppresses the stimulating effect of glucose in a competitive manner. Oligomycin
      removes the stimulating effect when used at concentrations causing the
      suppression of state 3 mitochondrial respiration by 20%. Under these conditions
      carboxyatracytyloside markedly enhances the glucose effect. It is concluded that
      glucose controls the oxidative phosphorylation, acting as an adenine nucleotide
      translocator.

PMID- 8155792
TI  - [A scientific society...the Scientific Society].

PMID- 8155793
TI  - [The efficacy of Hemoccult for screening colon cancer].

PMID- 8155794
TI  - [The Spanish version and pilot study of a telephone test of cognitive status for
      evaluation and screening in dementia assessment and follow-up].
AB  - OBJECTIVE: To adapt the telephone interview for cognitive status using the Mini
      Mental Status Examination as criterium validity, replicating the original
      development of the test. DESIGN: A quasi-experimental study with independent
      groups, and a correlational study between both tests and test-retest. SITE.
      Granada City. PARTICIPANTS: 62 Older population in chronic attention programs of
      Health Center 15 of them with dementia diagnosis. MEASUREMENTS AND MAIN RESULTS:
      Significant statistical differences were found in test scores for dementia
      patients group, a mild criterium validity (0.65), a high feasibility (0.83) and
      sensibility (0.77) and a mild specificity (0.60). A significant statistical
      difference was found between Spanish and USA control groups scores. CONCLUSIONS:
      The adaptation of the test was done and it seems an useful test in dementia
      studies but is necessary to replicate and more studies about the test.

PMID- 8155795
TI  - [Vaccinations in adults: the coverage of the users of a health center].
AB  - OBJECTIVE: To find the cover and records of recommended adult vaccinations and to
      identify possible causes of deficient cover. DESIGN: A descriptive crossover
      study using analysis of histories and a questionnaire. SETTING: General Medical
      and Nursing stations at the urban Guadalajara-Sur Health Centre. PATIENTS: Those
      people over 15 and with a prior appointment who were treated at the stations. A
      random selection of 352 patients. Final size: 275 patients (78.1%). MEASUREMENTS
      AND MAIN RESULTS: 20.5% +/- 4.9 of the population surveyed had been correctly
      vaccinated against tetanus. There was better cover of males (p < 0.05) and under
      45s (p < 0.001; Confidence level--95%). 41.8% +/- 13.6 of indicated patients
      stated that they had been vaccinated against German measles, while 79.5% +/- 7.0
      had received an anti-flu vaccination in the last campaign. Between 5 and 21%,
      according to age groups, possessed a vaccination card, with the levels noted in
      the medical records oscillating between 5.7% and 38.6%, respectively, for German
      measles and flu vaccination. Causes cited for non-vaccination were: ignorance in
      the cases of anti-tetanus (87.3%) and German measles (97%), carelessness (40%) or
      rejection (26.7%) for the anti-flu. CONCLUSIONS: Only anti-flu vaccination
      reaches acceptable coverage and understanding among our Centre's adult users,
      lack of knowledge being the main problem cited. We consider the recording level
      insufficient, both in clinical notes and on the vaccination cards. An intensive
      information campaign by health workers is needed, along with widespread
      vaccination to correct these deficiencies and reach the optimum coverage.

PMID- 8155796
TI  - [The utilization of health services and the motives for consultation as
      indicators of family dysfunction].
AB  - OBJECTIVE: To analyse the relationship between the reasons for seeking care on
      demand and use of the health services on the one hand and disturbances in the
      family dynamic, on the other, with an attempt to determine indicators of family
      dysfunction. DESIGN: Crossover descriptive study where the sample was obtained by
      systematic sampling. The family APGAR test was applied to the whole sample, along
      with an analysis of the use of services and the reasons for attendance. SETTING:
      Almanjayar Health Centre during the first 6 months of 1992. PATIENTS: 356
      patients over 18. MEASUREMENTS AND MAIN RESULTS: We confirmed that the likelihood
      of belonging to a dysfunctional family was 77%, with a risk of 6.5 for hyper and
      normal users. Regarding reasons for seeking care, those who attended because of
      ill-defined signs and symptoms are 6.21 times more likely to present a family
      dysfunction than the rest of those interviewed. Patients with ill-defined
      symptoms or psychiatric disorders who are hyper-users are 7.20 times more likely
      to present some family dysfunction. CONCLUSIONS: It will be useful to carry out a
      study of family function among hyper-users, those who attend because of ill
      defined signs and symptoms and people with mental health problems.

PMID- 8155799
TI  - [New information technologies and their application in primary health care].

PMID- 8155797
TI  - [An epidemiological study on unwanted pregnancy].
AB  - OBJECTIVE: To define the profile of the woman with an unwanted pregnancy (UWP)
      and to analyse differences between wanted pregnancies (WP) and UWP. DESIGN:
      Longitudinal and retrospective observation study. SETTING: La Chana Health
      Centre, Granada. PATIENTS: 511 pregnancies. MEASUREMENTS AND MAIN RESULTS:
      Pregnant women were grouped according to whether their pregnancy was WP or UWP.
      29.4% of all pregnancies were UWP. 70.5% of pregnancies in under-19s and 75% in
      over-35s are UWP (chi2 = 12.24; p = 0.00046 regarding the 19 to 35 age group).
      Women with WP first attend for prenatal care before women with UWP (chi 2 = 10.5;
      p = 0.0018). CONCLUSIONS: There is a high proportion of UWP, especially among
      women under 19 and over 35. We defined two profiles of women at risk of UWP.

PMID- 8155798
TI  - [A quality evaluation in requests for thoracic radiology in chronic pathology at
      a health center].
AB  - OBJECTIVE: To improve the quality of thoracic x-ray requests during chronic
      illness, presenting criteria for indication in HTA, LCFA and TBC. DESIGN:
      Intervention study of quality improvement. SETTING: Can Misses Health Centre in
      Ibiza. PARTICIPANTS: The General Practitioners at the above centre. MEASUREMENTS
      AND MAIN RESULTS: In this study we proposed to evaluate the work of the doctors
      at our Health Centre in correctly requesting x-ray explorations on the basis of
      two explicit, standard criteria: 1) the reason for the thorax x-ray request must
      be stated in the clinical notes. 2) Thorax x-rays requested for LCFA, HTA and TBC
      must be correctly indicated. CONCLUSION: The use of structured criteria in thorax
      x-ray requests for chronic patients appears to lead to greater quality in
      requests for this complementary exploration.

PMID- 8155801
TI  - [Errors in the composition of pharmaceutical specialties in the vade mecum].

PMID- 8155800
TI  - [Hospital emergencies coming from a penitentiary center].

PMID- 8155802
TI  - [Apropos the diagnostic criteria on alcohol abuse and dependence].

PMID- 8155804
TI  - [Obstetrical echography and primary care].

PMID- 8155803
TI  - [The current indications for colchicine in gout].

PMID- 8155805
TI  - [Trochanteric bursitis in primary care].

PMID- 8155807
TI  - [The presence in a hospital emergency service of patients who were previously
      cared for in an outpatient emergency service].

PMID- 8155806
TI  - [Where to set the limit of excessive alcohol consumption?].

PMID- 8155808
TI  - [The utilization of laboratories for healthy persons at the primary care level].

PMID- 8155810
TI  - [The definition of the disease of bronchial asthma].

PMID- 8155809
TI  - [Undergraduate education in primary care].

PMID- 8155811
TI  - [Informatics as a teaching technic].

PMID- 8155812
TI  - [Geriatric AIDS: 2 new cases].

PMID- 8155813
TI  - Tryptophan photophysics in rabbit skeletal myosin rod.
AB  - The fibrous region of myosin (myosin rod) is an alpha-helical, two-stranded
      coiled-coil made up of identical hydrophobic d sites in the heptad repeat that
      forms the basis for hydrophobic dimerization. The fluorescence excitation and
      emission spectra of rod in high salt buffer (where the rod exists as a coiled
      coil monomer) at 20 degrees C are red- and blue-shifted, respectively, from the
      comparable spectra of N-acetyl-tryptophanamide or L-tryptophan. These spectral
      shifts, as well as red-shifts in the emission spectra induced by excitation on
      the red edge of the absorption or by increases in temperature, indicate that (on
      average) the tryptophans are partially exposed to aqueous solvent yet in contact
      with the protein matrix. The tryptophan intensity decays show an unusual bimodal
      distribution; the major species has a discrete lifetime of about 5.2 ns while the
      minor species exhibits a complex decay with a broad (3.4 ns full width at half
      maximum) Gaussian distribution of lifetimes centered around 1.3 ns. The long
      lifetime species has a blue-shifted excitation and red-shifted emission
      characteristic of the indole chromophore in a polar (probably aqueous)
      environment while the short lifetime species has the spectral parameters
      characteristic of indole in a non-polar environment. Although assignment of these
      lifetime species to particular tryptophans in the rod is problematic, this study
      indicates that the coiled-coil interface presents a complex heterogeneous
      environment that may undergo rapid conformational mobility.

PMID- 8155814
TI  - Calculation of the circular dichroism spectrum of cyclo-(L-tyr-L-tyr) based on a
      molecular dynamics simulation.
AB  - Theoretical calculations of CD spectra have generally assumed a single
      conformation, or a small number of conformers with Boltzmann averaging. Solvent
      effects on both the conformation and the CD have been neglected. In this work, we
      have calculated the CD spectrum of cyclo(L-Tyr-L-Tyr) in aqueous solution, taking
      dynamics and solvation into account. Starting geometries with chi 1 approximately
      300 degrees or 60 degrees for both Tyr side chains were derived from MNDO/MOPAC,
      followed by energy minimization using GROMOS. After addition of 368 water
      molecules, the system was simulated for 1000 ps at 300 K using GROMOS. In
      addition to the starting conformer, two other conformers were observed during
      each simulation. However, each trajectory gave a distinct set of conformers.
      Rotational strengths were calculated for the cyclic dipeptide at each ps along
      the trajectories, using the matrix method. The CD spectra calculated from these
      rotational strengths were averaged over the trajectories. Agreement is very good
      for the strong negative band near 200 nm, while for the lower energy bands (near
      230 and 280 nm), the signs are correct, but the magnitudes are too low. The
      spectrum calculated from a Boltzmann-weighted average over the in vacuo
      MNDO/MOPAC conformers was in poor agreement with experiment. Although the solvent
      did not significantly affect the rotational strength calculated for a given
      conformer, it is essential to include the solvent in the MD simulations because
      it affects the relative energies of the conformers and promotes transitions among
      them.

PMID- 8155815
TI  - The main transition of dipalmitoylphosphatidylcholine monolayers: a liquid
      expanded to solid condensed high order transformation.
AB  - We have investigated the orientation processes of a fluorescent probe, 12-(9
      anthroyloxy)stearic acid (12-9-AS), embedded in a dipalmytoylphosphatidylcholine
      (DPPC) monolayer spread at the air/water interface. These orientation processes
      are represented by an orientation parameter defined as the ratio of two
      dimerization constants obtained from fluorescence experiments using two
      perpendicular linearly polarized incident light beams. The orientation parameter
      shows three particular domains of orientation during the compression of the DPPC
      film, these domains being separated by two drastic changes in the orientation
      parameter, one located at the LC/SC transition point (0.48 nm2.molecule-1) and
      the other at the end of the LE/LC transition region (0.58 nm2.molecule-1).
      Attribution of the phases implicated in the bidimensional liquid/solid
      transformation was thus revisited. Therefore, from the present results together
      with results gathered in the literature, we show that the main monolayer phase
      transition of DPPC implies a transformation from a molecular state having a
      characteristic area ALE (phase LE) to a molecular state of characteristic area
      ASC (phase SC) with an intermediate molecular state of characteristic area ALC
      (phase LC). During the main monolayer transformation (the LE/SC phase transition)
      the highly condensed domain with a molecular area ASC (0.48 nm2.molecule-1) are
      thus surrounded by a region of interfacial lipid of molecular area ALC (0.58
      nm2.molecule-1) distributed in a fluid phase of characteristic area ALE (0.74
      nm2.molecule-1).

PMID- 8155816
TI  - Thermodynamics of the hydrolysis of penicillin G and ampicillin.
AB  - Apparent equilibrium constants and calorimetric enthalpies of reaction have been
      measured for the beta-lactamase catalyzed hydrolysis of penicillin G(aq) and
      ampicillin(aq) to penicillinoic acid(aq) and to ampicillinoic acid(aq),
      respectively. High-pressure liquid-chromatography and microcalorimetry were used
      to perform these measurements. The results for the reference reactions at T =
      298.15 K and Im = 0 are: Ko = (9.4 +/- 3.1) x 10(-7), delta rGo = (34.4 +/-
      1.0)kJ mol-1, delta rHo = -(73.7 +/- 0.4)kJ mol-1, and delta rSo = -(363 +/- 4) J
      K-1 mol-1 for penicillin G-(aq) + H2O(1) = penicillinoic acid2-(aq) + H+(aq); Ko
      = (6.0 +/- 3.0) x 10(-6), delta rGo = (29.8 +/- 1.7) kJ mol-1, delta rHo = -(70.0
      +/- 7.5) kJ mol-1, and delta rSo = -(335 +/- 26) J K-1 mol-1 for ampicillin-(aq)+
      H2O(1) = ampicillinoic acid2-(aq)+H+(aq). Calorimetric enthalpies of reaction for
      the beta-lactamase catalyzed hydrolysis of cephalosporin C have also been
      measured but the reaction products have not been identified and the measured
      enthalpies cannot be assigned to a specific reaction. Acidity constants for
      ampicillin, penicillin G, ampicillinoic acid, and penicillinoic acid are also
      reported. A strain energy of 116 kJ mol-1 for the beta-lactam ring is obtained
      from thermochemical data.

PMID- 8155817
TI  - Thermodynamic properties of peptide solutions. Part 11. Partial molar isentropic
      pressure coefficients in aqueous solutions of some tripeptides that model protein
      side-chains.
AB  - The partial molar isentropic pressure coefficients at infinite dilution K
      infinity s,2 (K infinity s,2 = -(delta V infinity 2/delta p)s, where V infinity 2
      is the partial molar volume at infinite dilution) have been determined for nine
      tripeptides in aqueous solution at 25 degrees C. The tripeptides are all of
      sequence glycyl-X-glycine, where X is an amino acid. These K infinity s,2
      results, in conjunction with those of glycylglycylglycine, were used to estimate
      the amino acid side-chain contributions to K infinity s,2 of peptides. These side
      chain contributions are critically compared with previous estimates based on K
      infinity s,2 data for the amino acids. The variation in the side-chain
      contributions derived using the peptide K infinity s,2 results has been
      rationalized in terms of likely peptide-solvent interactions.

PMID- 8155818
TI  - Metabolic pathways of 1-butyl [3-13C]acrylate. Identification of urinary
      metabolites in rat using nuclear magnetic resonance and mass spectroscopy.
AB  - 1-Butylacrylate, an industrial monomer, is rapidly metabolized by
      carboxylesterase-catalyzed hydrolysis to acrylic acid and 1-butanol. Acrylic acid
      enters the intermediary metabolism and is efficiently degraded to carbon dioxide
      as the metabolic end product. To obtain a virtually complete metabolic pattern,
      rats were dosed by a single intraperitoneal dose of 1 mmol/kg 1-butyl [3
      13C]acrylate. The urine was then analyzed by a one-dimensional 1H-detected and
      two-dimensional 1H-13C shift-correlated heteronuclear multiple-quantum NMR
      experiment. In this experiment, three urinary metabolites, namely, 3
      hydroxypropanoic acid, N-acetyl-S-(2-carboxyethyl)cysteine, and N-acetyl-S-(2
      carboxyethyl)cysteine sulfoxide, were identified comparing their 1H and 13C
      chemical shifts with those of authentic standards. In another experiment, to
      enhance minor metabolic pathways, rats were dosed with 0.25 mmol/kg of a
      carboxylesterase inhibitor, tri-o-tolyl phosphate, prior to 0.5 mmol/kg butyl [3
      13C]acrylate. Under these conditions, N-acetyl-S-(2-carboxyethyl)cysteine, N
      acetyl-S-[2-(butoxycarbonyl)-ethyl]cysteine, and N-acetyl-S-(2
      carboxyethyl)cysteine sulfoxide were found in urine. No metabolites which would
      arise from a possible metabolic activation of 1-butyl acrylate to 1-butyl
      oxiranecarboxylate and its subsequent hydrolysis or glutathione conjugation were
      found. It is estimated that any metabolite amounting to more than 1% of the dose
      should be detected under these conditions. To study the routes by which BA enters
      the intermediary metabolism, incorporation of the label into urinary carboxylic
      acids was followed by GC/MS. Significant enrichment was found in 3
      hydroxypropanoic acid and citric and isocitric acid but not in lactic
      acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155819
TI  - Halide-catalyzed cis product formation in the hydrolysis of anti-benzo[a]pyrene
      diol epoxide and its alkylation of poly(A).
AB  - The carcinogen 7-r,8-t-dihydroxy-9-t,10-t-epoxy-7,8,9,10-
      tetrahydrobenzo[a]pyrene (anti-BPDE) forms diastereomeric cis and trans products
      in its reactions with nucleic acids and water (adducts and tetrols,
      respectively). The effects of salts, buffers, and DNA on the hydrolysis product
      ratio were tested. Halide ions increase the cis-tetrol/trans-tetrol ratio, with
      the order of effectiveness being I > Br > Cl >> F. No cation effect was apparent.
      Non-halide salts of strong acids increase the ratio to a small degree. Buffers
      decrease the ratio, with phosphate being more effective than cacodylate. DNA also
      reduces the ratio, with denatured DNA being more potent than native DNA. Halide
      ions appear to catalyze cis-tetrol formation via trans halohydrin intermediates.
      At the lowest halide concentrations which significantly raise the product ratio,
      and at all levels of chloride ion, the rate of anti-BPDE hydrolysis is not
      greatly increased, indicating that the halide ions are reacting primarily with
      the BPDE carbocation formed in the rate-determining step. At higher
      concentrations, iodide ion and, to a lesser degree, bromide ion significantly
      accelerate hydrolysis, indicating that BPDE undergoes SN2 attack by these ions.
      Chloride ion was also found to increase the proportion of cis adducts formed
      between anti-BPDE and poly(A). The cis adduct/trans adduct ratio was quadrupled
      by 0.5 M NaCl. This suggests that chlorohydrins can be intermediates in the
      alkylation of nucleic acids by epoxides of polycyclic aromatic hydrocarbons.

PMID- 8155820
TI  - Effects of the peroxisome proliferator perfluoro-n-decanoic acid on hepatic
      gluconeogenesis and glycogenesis: a 13C NMR investigation.
AB  - Carbon-13 NMR spectroscopy was used to study the effects of the peroxisome
      proliferator perfluoro-n-decanoic acid (PFDA) on hepatic carbohydrate metabolism
      in male Fischer-344 rats. The data indicate that PFDA-treated rats display an
      inhibition in hepatic [1-13C]glucose and [3-13C]alanine utilization on day 5
      posttreatment. PFDA rats show hepatic mean glucose and alanine intensities which
      are significantly greater (ca. 10-100%) than controls. With [1-13C]-glucose as
      substrate, PFDA rats show severe to complete inhibition in glycogenesis on days 3
      and 5 posttreatment. With [3-13C]alanine as substrate, both groups show
      functional gluconeogenesis and glycogenesis; however, treated rats show a more
      transient and less intense C1-glycogen resonance relative to control. These data
      suggest that PFDA inhibits either the hepatocellular transport of glucose and/or
      its phosphorylation by glucokinase. The effect of PFDA on TCA cycle activity was
      determined by monitoring the flow of [3-13C]alanine into glutamate. The relative
      activity of pyruvate carboxylase (PC) versus pyruvate dehydrogenase (PDH) is
      represented by the ratio of the glutamate NMR signal intensities (C2 + C3)/C4.
      PFDA rats show a lower (C2 + C3)/C4 glutamate ratio, suggesting greater relative
      activity of PDH versus PC in PFDA rats relative to controls. Differences in PDH
      activity may arise from differences in lipolytic activity. Our data suggest a
      dysfunction in fatty acid metabolism in PFDA rats and corroborate other studies
      which show that PFDA inhibits fatty acid oxidation.

PMID- 8155821
TI  - An o-quinone form of estrogen produces free radicals in human breast cancer
      cells: correlation with DNA damage.
AB  - The o-quinone forms of 2,3- and 3,4-catechol estrogens have been implicated in
      the carcinogenicity of these hormones. The concomitant production of reactive
      oxygen species during reduction of the o-quinone estrogens has been inferred to
      play a mechanistic role in their mutagenic potential. Conclusive evidence
      documenting the production of hydrogen peroxide, the hydroxyl radical, and the
      estrone 3,4-semiquinone in estrone 3,4-quinone (3,4-EQ)-treated human breast
      cancer subcellular fractions was demonstrated in the absence of exogenously added
      catalysts. Subcellular fractions of MCF-7 cells treated with 3,4-EQ and NADPH,
      including nuclei, mitochondria, and microsomes, were shown to support significant
      amounts of hydrogen peroxide production. Hydrogen peroxide production in 3,4-EQ
      treated cellular fractions and the chromosomal DNA damage induced in 3,4-EQ
      treated MCF-7 cells were abolished by the addition of catalase. A significant and
      potentially physiologically relevant spontaneous reduction of 3,4-EQ by NADPH
      resulting in hydrogen peroxide production was demonstrated. The results
      unequivocally demonstrate that free radicals are produced during the metabolism
      of estrone 3,4-quinone in human cells.

PMID- 8155823
TI  - Identification of the major lesion from the reaction of an acridine-targeted
      aniline mustard with DNA as an adenine N1 adduct.
AB  - DNA adducts of two acridine-linked aniline half-mustards have been isolated and
      identified. The compound where the half-mustard is attached to the DNA-targeting
      acridine moiety by a short linker chain alkylates both double- and single
      stranded DNA exclusively at guanine N7, as do the majority of known aromatic and
      aliphatic nitrogen mustards. The longer-chain analogue, also containing a more
      reactive half-mustard, shows a strikingly different pattern, alkylating double
      stranded DNA to yield primarily (> 90%) the adenine N1 adduct, together with <
      10% of the adenine N3 adduct and only trace amounts of the guanine N7 adduct. In
      the presence of MgCl2 (which is known not to inhibit the interaction of drugs at
      minor groove sites), the adenine N3 adduct is the major product. The latter
      compound is the first known aniline mustard (and apparently the first known
      alkylating agent of any type) to preferentially alkylate adenine at the N1
      position in duplex DNA. These results are consistent with previous work [Prakash
      et al. (1990) Biochemistry 29, 9799-9807], which showed that the preferred site
      of DNA alkylation by the corresponding long-chain acridine-linked aniline bis
      mustards in general was at major groove sites of adenines and identifies the
      major site of alkylation as adenine N1 and not N7. This selectivity for adenine
      N1 alkylation is suggested to result from a preference for the acridine mustard
      side chain of these compounds to project into the major groove following
      intercalation of the acridine, coupled with structural distortion of the DNA
      helix to make the N1 positions of adenines adjacent to the intercalation sites
      more accessible.

PMID- 8155822
TI  - Base sequence selectivity in the binding of 7(R),8(S)-dihydroxy-9(S),10(R)-epoxy
      7,8,9,10-tetrahydrobenzo[a]pyrene to oligodeoxyribonucleotide duplexes.
AB  - The effect of nucleotide sequence on the binding of 7(R),8(S)-dihydroxy
      9(S),10(R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] to the
      exocyclic amino group of deoxyguanosine was investigated in duplexes formed by
      self-complementary oligodeoxyribonucleotide decamers which contained two
      deoxyguanosines (dGs) within unique sequences. A 35S-postlabeling procedure was
      developed for analysis of (+)-anti-BPDE adducts as dinucleotides containing 5'
      (+)-anti-BPDE-dG adducts. This allows identification of the 3' neighbor of the
      reacted guanine and permits quantitation of the binding of (+)-anti-BPDE to each
      specific guanine in the oligodeoxyribonucleotide duplexes. Of all the central dG
      containing sequences studied, dG surrounded by deoxycytidines (CGC) reacted to
      the greatest extent: over 4-fold more (+)-anti-BPDE bound to this central dG
      compared to the least reactive deoxyguanosine (AGT). (+)-anti-BPDE exhibited a
      preference for binding to a central deoxyguanosine when either the 5' or 3'
      neighbor was deoxyguanosine. The binding of (+)-anti-BPDE to
      oligodeoxyribonucleotide duplexes containing different numbers of consecutive dGs
      was analyzed in order to determine how the length of these sequences influences
      binding. Increases in the length of consecutive deoxyguanosine residues from 3 to
      5 had little effect on the quantity of (+)-anti-BPDE bound to dG above that
      expected from the presence of a neighboring dG and an increase in the number of
      dG residues available for reaction. The results obtained with these
      oligodeoxyribonucleotide duplexes were consistent with the data available for the
      reaction of (+)-anti-BPDE with DNA, indicating that these duplexes are a valuable
      model for studying the effect of base sequence on the interaction of BPDE isomers
      with DNA. The dinucleotide postlabeling technique developed for these studies,
      with appropriate oligodeoxyribonucleotides and chromatographic conditions, will
      be useful for determining the effect of base sequence on the binding of other
      hydrocarbon diol epoxides as well as other reactive hydrocarbon metabolites to
      deoxyguanosine or deoxyadenosine in oligodeoxyribonucleotide duplexes and
      fragments of DNA.

PMID- 8155824
TI  - The reactions of ozone with proteins and unsaturated fatty acids in reverse
      micelles.
AB  - Sodium oleate cosolubilized with lysozyme in reverse micellar solutions is shown
      to inhibit the ozone-mediated oxidation of tryptophan residues in the protein.
      The magnitude of inhibition by oleate, which is an indirect measure of the
      fraction of ozone that reacts with oleate instead of the protein, is predictable
      using a kinetic model that is based on the concentrations and the reactivities
      toward ozone of the amino acid residues in lysozyme and the double bond in
      oleate. Oleate (2 mM), linoleate (1 mM), linolenate (0.67 mM), and gamma
      linolenate (0.67 mM) all inhibit the ozonation of lysozyme similarly; this
      indicates that ozone reacts with double bonds in mono-, di-, or polyunsaturated
      fatty acids at approximately the same rate. All these fatty acids reside at the
      micellar interface with their head groups facing inward toward the dispersed
      water pools and the hydrocarbon tails projecting into the bulk, continuous
      organic phase. Various short-chain 2-, 3-, and 4-alkenoic acids that reside
      predominantly in the water pools, and long-chain alkenes that reside in the bulk
      organic solvent, have a similar inhibitory effect on the ozone-mediated oxidation
      of tryptophan residues in lysozyme. Thus, the location of olefinic compounds in
      the micelles or bulk organic phase per se does not influence the rate of reaction
      in this reverse micellar system. A number of proteins that reside in the water
      pools of reverse micelles are found to behave similarly to lysozyme, including
      albumin, carbonic anhydrase, beta-casein, alpha-chymotrypsin, alpha-lactalbumin,
      beta-lactoglobulin, papain, apotransferrin, trypsin, and trypsin
      inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155825
TI  - The mechanism of nucleophilic substitution of alkylpyrroles in the presence of
      oxygen.
AB  - The mechanism of oxidation of alkylpyrroles (1a-d) by molecular oxygen in the
      presence of nucleophiles is explored. Contrary to previous reports, oxidation of
      these pyrroles resulted in dimers with both the aromatic rings intact. In the
      presence of additional nucleophiles these pyrroles entered into substitution
      reactions. With 2-mercaptoethanol the site of substitution on 1a was the 3
      position rather than the side chain. The first-order rate constant for this
      reaction in acetonitrile with excess oxygen was found to be (7.8 +/- 1.2) x 10(
      7) s-1. The rate was unaffected by the presence of either BHT or catechol.
      Replacing hydrogens at all the potential sites of reaction by deuterium (as in
      1aD) did not reduce the rate of substitution. However, the product suffered loss
      of deuterium from all sites. These observations support a mechanism involving the
      formation of a complex 20 between the pyrrole and triplet oxygen. Electron
      transfer from the pyrrole to oxygen in the rate-limiting step is followed by the
      generation of pyrrolylmethyl intermediate 23 that can react with available
      nucleophiles including unoxidized pyrroles.

PMID- 8155827
TI  - Estrogen quinones: reaction with propylamine.
AB  - Reaction of propylamine with 2,3-estrone o-quinone (2,3-EQ) and 3,4-estrone o
      quinone (3,4-EQ) gave a complex mixture of mostly unidentifiable products.
      Several reaction products were isolated and identified using spectroscopic
      techniques. With 3,4-EQ, both 1,2- and 1,6-Michael addition reactions were
      observed in which 4-hydroxyestradiol, an estrogen oxazole, and a violet compound
      identified as the iminoquinone adduct that was obtained by condensation of one
      molecule of an estrogen o-aminophenol with the 1,6-Michael addition product of
      propylamine to 3,4-EQ were identified. Unlike reactions of 3,4-EQ, only 1,2
      Michael addition reactions were observed with 2,3-EQ leading to the formation of
      2-hydroxyestradiol, two monoiminoquinone compounds, and a bisiminoquinone
      product.

PMID- 8155826
TI  - Formation of the acrolein-derived 1,N2-propanodeoxyguanosine adducts in DNA upon
      reaction with 3-(N-carbethoxy-N-nitrosamino)propionaldehyde.
AB  - 3-(Methylnitrosamino)propionaldehyde (MNPA) is a carcinogenic nitrosamine formed
      by nitrosation of arecoline, a major alkaloid in areca nut which is a constituent
      of betel quid. While DNA adducts of its analogue, 3
      (methylnitrosamino)propionitrile, have been characterized, little is known about
      the structures of DNA adducts by MNPA. In this paper, we report that the acrolein
      derived 1,N2-propanoguanine adducts are formed upon incubating deoxyguanosine or
      DNA with 3-(N-carbethoxy-N-nitrosamino)propionaldehyde, a stable carbamate
      precursor of the metabolically activated MNPA. The identities of these adducts
      were confirmed by HPLC co-migration, by their NMR and UV spectra, and by chemical
      properties as compared with those of the synthetic standards. Analogous results
      were obtained from the reaction of the carbamate with calf thymus DNA. Upon acid
      or enzyme hydrolysis of the carbamate-modified DNA, acrolein-guanine adducts were
      detected, and the levels were quantitated. Again, the identities of the adducts
      were verified by co-chromatography with the standards, by UV spectroscopy, or by
      the ring-opening with NaOH/NaBH4. Consistent with its ability to modify DNA, the
      carbamate was found to be mutagenic in Salmonella tester strains. These results
      show that acrolein is a likely metabolite from the activation of MNPA and that
      the formation of 1,N2-propanoguanine adducts may contribute to the mutagenicity
      of the carbamate of MNPA.

PMID- 8155828
TI  - Structure-genotoxicity relationships of allylbenzenes and propenylbenzenes: a
      quantum chemical study.
AB  - Quantum mechanical calculations at the semiempirical level (AM1 method) were
      conducted for estragole (1), methyleugenol (2), safrole (3), alpha-asarone (4),
      beta-asarone (5), elemicin (6), allylbenzene (7), eugenol (8), trans-anethole
      (9), isosafrole (10), and myristicin (11), and the results compared with the
      known genotoxicity of 1-6 and the absence of genotoxicity of 7-11 (unscheduled
      DNA synthesis assay). The various compounds showed no significant differences in
      the relative stability of the radical species formed as intermediates in C-sp3
      hydroxylation (delta HR(radical)) and in the corresponding enthalpy of activation
      (delta H++). In contrast, the carbonium ions of the genotoxic congeners 1-6 were
      shown to be comparatively more stable than those of the inactive compounds 7-11,
      with the exception of eugenol (8). The inactivity of this compound could be due
      to a very rapid stabilization of the carbonium ion by deprotonation to form a
      quinone methide, as suggested by quantum chemical calculations. The relative
      stability of the carbonium ion thus appears to be one of the key factors in the
      genotoxicity of allylbenzenes and propenylbenzenes.

PMID- 8155829
TI  - Neuropathy target esterase inhibitors: enantiomeric separation and
      stereospecificity of 2-substituted-4H-1,3,2-benzodioxaphosphorin 2-oxides.
AB  - 2-Substituted-4H-1,3,2-benzodioxaphosphorin 2-oxides (2-substituted-BDPOs) are
      known to be potent neuropathy target esterase (NTE) inhibitors (I50s for the
      racemates of 0.2-3 nM) when the 2-substituents are n-alkyl (C5-C12), N-alkoxy (C7
      C10), or p-n-alkylbenzyl (C3 and C4). The list of potent inhibitors (I50s < 3 nM)
      is expanded by the new n-alkylamino (C9) and n-alkylthio (C5, C7, and C9) analogs
      reported here. The optimal chain length of the 2-substituent is about 10 atoms in
      the alkylamino and alkylthio series as in our previous study on alkyl and alkoxy
      moieties. In contrast, an I50 of 60 nM is reported for o-methylphenoxy-BDPO, the
      neuropathic metabolite of tri-o-cresyl phosphate (TOCP). In addition to
      substituent effects, each of these compounds contains two enantiomers of unknown
      stereospecificity as NTE inhibitors. Separation by chiral HPLC with the CHIRALCEL
      OC column and hexane-2-propanol eluent gives individual enantiomers of > 98% e.e.
      and a stereospecificity for NTE inhibition depending on the type and chain length
      of the 2-substituent; e.g., the ratio for inhibitory potency of the individual
      enantiomers is 1.7-fold for nonylthio, 1255-fold for nonylamino, and 9-fold for
      the TOCP metabolite. In comparing enantiomeric pairs of BDPOs with alkyl, alkoxy,
      alkylamino, alkylthio, benzyl, p-butylbenzyl, o-methylphenoxy, or phenyl as the 2
      substituent, the more retained enantiomer in HPLC is always the better NTE
      inhibitor (in a series of twenty-two pairs) and housefly toxicant (based on two
      pairs) than the less retained one.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155831
TI  - Bisdihydrodiols, rather than dihydrodiol oxides, are the principal microsomal
      metabolites of tumorigenic trans-3,4-dihydroxy-3,4-dihydrodibenz[a,h]anthracene.
AB  - Several studies on metabolism and biological activity of tumorigenic
      dibenz[a,h]anthracene (DBA) and its derivatives have led to the conclusion that
      the M-region dihydrodiol, trans-3,4-dihydroxy-3,4-dihydro-DBA (DBA-3,4
      dihydrodiol), is the precursor of the ultimate mutagenic and tumorigenic
      metabolite of DBA with the presumed structure of a bay-region dihydrodiol oxide.
      Incubations of DBA-3,4-dihydrodiol (50 microM) with the microsomal hepatic
      fraction of Sprague-Dawley rats pretreated with Aroclor 1254 yielded more than 13
      metabolites upon separation by HPLC. anti-3,4-Dihydroxy-1,2-epoxy-1,2,3,4
      tetrahydro-DBA [0.27 nmol/(nmol of P450.15 min)] could be identified for the
      first time by UV spectroscopy, by cochromatography with the synthetic reference
      compound, and by its nonenzymatic hydrolysis to r-1,t-2,t-3,c-4-tetrahydroxy
      1,2,3,4-tetrahydro-DBA, while firm evidence for the presence of the
      diastereomeric syn-dihydrodiol oxide was not obtained. Major microsomal
      metabolites of the M-region dihydrodiol were however three bisdihydrodiols:
      trans,trans-3,4:8,9-tetrahydroxy-3,4,8,9-tetrahydro-DBA [0.32 nmol/(nmol of
      P450.15 min)], trans,trans-3,4:10,11-tetrahydroxy-3,4,-10,11-tetrahydro-DBA [DBA
      3,4:10,11-bisdihydrodiol; 1.44 nmol/(nmol of P450.15 min)], and trans,trans
      3,4:12,13-tetrahydroxy-3,4,12,13-tetrahydro-DBA [0.70 nmol/(nmol of P450.15
      min)], whose structures were verified by UV and mass spectrometry as well as
      cochromatography with synthetic reference compounds and by the observation that
      they were not formed when epoxide hydrolase was inhibited (1,1,1-trichloro-2
      propene oxide, 1 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155834
TI  - Cloning of thienamycin biosynthetase genes from Streptomyces cattleya.
AB  - A mutant Y3 blocked in the thienamycin biosynthetic pathway was obtained from
      thienamycin producing strain Streptomyces cattleya by NTG treatment. Preliminary
      cloning system has been established on the basis of studies on the conditions for
      protoplast formation, regeneration, as well as DNA transformation for Y3 mutant
      strain. The shotgun cloning was carried out from S. cattleya using pIJ680 as a
      vector and the Y3 mutant as a host. The transformant No. 12 produced a
      thienamycin-like substance identified by paper chromatography and HPLC analysis.
      A recombinant plasmid p6BC12, which has molecular size of 9.8kb and an insert of
      4.5kb, could be recovered. Southern hybridization confirmed that the transformant
      No. 12 harbors the recombinant plasmid p6BC12. The intermediate accumulated by Y3
      mutant was identified as a polypeptide. The product of transformant containing
      p6BC12 could turn this polypeptide to a bioactivity substance in vitro. This gene
      can hybridizate with S. lipmanii IPNS gene. We presume that a cyclase gene from
      S. cattleya was cloned according to the function of the expression product.

PMID- 8155835
TI  - Studies on oxygen transfer process in animal cell culture bioreactor.
AB  - The oxygen transfer rates were investigated systematically in the CellCul-20A
      bioreactor with the device of cage aeration in this paper. The temperature,
      rotating speed, aeration rate and foam breaker, which affected the rate of oxygen
      transfer were studied, respectively. The mass transfer rate increased
      significantly with the aeration while the foam breaker had a negative effect on
      kLa, especially in a cell culture medium with 5% (v/v) calf serum. The oxygen
      transfer coefficients of surface and deep aerations were correlated, based on the
      experimental data.

PMID- 8155833
TI  - Sequence dependence of benzo[a]pyrene diol epoxide-DNA adduct conformer
      distribution: a study by laser-induced fluorescence/polyacrylamide gel
      electrophoresis.
AB  - Low-temperature laser-induced fluorescence techniques in combination with
      polyacrylamide gel electrophoresis (LIF/PAGE) were used to study the binding of (
      )-anti- and (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide (anti-BPDE) to
      several sequence-defined duplex oligomers. Two of the oligomers contain central
      5'-RAGGAR-3' sequences (R = purine) which appear to be frequently mutated by
      racemic (+/-)-anti-BPDE in endogenous genes of cells cultured in vitro. Two
      contain a central 5'-CCGG-3' or 5'-TGGT-3' sequence which are strongly preferred
      for covalent binding but appear to be not so frequently mutated. Binding of the
      two enantiomers to the latter two sequences yielded a distribution of BPDE-N2-dG
      adduct conformations similar to those from binding to highly polymerized, random
      sequence DNA in vitro which, for (+/-)-anti-BPDE, means that the helix-external
      conformation of the N2-dG adduct is dominant. Binding of (-)-anti-BPDE to the 5'
      RAGGAR-3' sequences yielded more partially base-stacked and less base-stacked
      (quasi-intercalated) conformer than observed for random sequence DNA.
      Importantly, the (+)-anti-BPDE in binding to the more mutagenically inclined 5'
      RAGGAR-3' sequences yielded little external-type adduct in comparison to the
      other two sequences and random sequence DNA. Moreover, an unusually high
      proportion of the (+)-anti-BPDE adducts formed with the 5'-RAGGAR-3' sequences
      result from cis stereoaddition, which yields a partially base-stacked
      configuration. Since the (+)-anti-BPDE appears to be the more mutagenic, this
      result suggests a possible role of internal adduct conformations in mutagenesis.

PMID- 8155832
TI  - The effect of cytosol on liver microsomal metabolic activation and demethylation
      of N-nitrosodimethylamine.
AB  - The role of rat liver cytosol in the demethylation and metabolic activation of N
      nitrosodimethylamine (NDMA) was examined. Addition of cytosol to liver microsomes
      from pyridine-pretreated rats enhanced DNA alkylation by NDMA 10- to 14-fold over
      microsomes alone, while cytosol alone had little DNA alkylating activity. The
      cytosolic activity responsible for the enhancement of DNA alkylation was heat
      labile, required NADPH, and was not a general protein effect. Addition of cytosol
      to purified rabbit liver cytochrome P450 2E1 in a reconstituted system consisting
      of NADPH-cytochrome P450 reductase, 2E1, and phospholipid produced an 18-fold
      increase in DNA alkylation over that observed with the reconstituted system
      alone. The cytosolic activity responsible for the enhancement of DNA alkylation
      did not work by inhibition of lipid peroxidation, nor did the addition of cytosol
      affect the level of NADPH present in the reaction mixtures. Attempts to identify
      the cytosolic component(s) responsible for the DNA alkylation enhancing activity
      demonstrated no evidence for the involvement of sulfhydryl-dependent enzymes, a
      flavoprotein, or conjugating enzymes. Studies with semicarbazide and
      phenylhydrazine suggest that carbonyl groups may be involved in the cytosolic
      activity. Measurements of NDMA demethylation demonstrated that cytosol addition
      led to a significant decrease in formaldehyde production, indicating that cytosol
      was not enhancing the activation of NDMA to a DNA alkylating species by
      facilitating the cytochrome P450-catalyzed demethylation reaction, and suggested
      that a cytosolic reaction might be occurring at the expense of formaldehyde
      formation.

PMID- 8155830
TI  - Application of capillary liquid chromatography coupled with tandem mass
      spectrometric methods to the rapid screening of adducts formed by the reaction of
      N-acetoxy-N-acetyl-2-aminofluorene with calf thymus DNA.
AB  - Capillary liquid chromatography-continuous-flow fast atom bombardment mass
      spectrometry is applied to the detection of deoxynucleoside adducts of N-acetoxy
      N-acetyl-2-aminofluorene. In such a configuration, normal scan and tandem mass
      spectrometric techniques are shown to provide useful structural information for
      an N-acetyl-N-(deoxyguanosin-8-yl)-2-aminofluorene adduct standard for low-
      nanogram (low-picomole) amounts sampled. In addition, multiple reaction
      monitoring gives limits of detection below 25 pg (50 fmol) for this adduct,
      suggesting the potential for routine screening of intact deoxynucleoside adducts
      formed below the 1:10(6) level from as little as 1 mg of DNA. When applied to the
      analysis of the products of an in vitro reaction of calf thymus DNA with N
      acetoxy-N-acetyl-2-aminofluorene, these techniques are readily able to detect and
      supply structural data for the N2 and C8 deoxyguanosine adducts formed.

PMID- 8155836
TI  - Human myeloperoxidase gene cDNA cloning and expression in acute leukemia.
AB  - In this study, the light chain and a part of the heavy chain cDNA segment of
      human myeloperoxidase (MPO) were cloned with PCR and other DNA recombination
      techniques from HL-60 cell. The size of the cloned cDNA was 769 bp. A segment
      about 600bp of the cDNA was analyzed by DNA sequencing and showed no difference
      from the human MPO cDNA sequences published before. The MPO cDNA was used as a
      probe to study the MPO gene expression in leukemic cells. The Northern blot
      analysis and slot blot analysis of RNA isolated from leukemic cell lines and
      blast cells of acute leukemia showed that MPO gene expression correlated with
      myeloid lineage and might be used as a marker for the subclassification of acute
      leukemia.

PMID- 8155837
TI  - Catalysis of the hydrolysis of ethyl mandelate and esterification of alpha
      bromopropionic acid by lipase in microemulsions.
AB  - Candida cyclindracea lipase (CCL) was added to "sodium dodecyl sulfonate (AS)/n
      butanol/n-octane/n-octane" water-in-oil microemulsion to catalyze the hydrolysis
      of ethyl mandelate and the esterification of alpha-bromopropionic acid with n
      butanol, respectively. The catalytic activity of CCL in the above microemulsions
      was higher than that in the traditional oil/water biphasic systems. After
      hydrolysis for 48 h, the conversion rate of the reaction reached 90% and S
      mandelic acid, [alpha]D20-149.8 (C10; H2O), optical purity ca. 97%, was isolated.
      While after esterification for 6 h, the conversion rate of the reaction reached
      45%, and butyl-(R)-alpha-bromopropionate, [alpha]D20 18.2 (Cl; CHCl3), optical
      purity ca. 99%, was obtained.

PMID- 8155838
TI  - Extended Kalman filter (EKF) application in vitamin C two-step fermentation
      process.
AB  - Based on kinetic model study of vitamin C two-step fermentation, the extended
      Kalman filter (EKF) theory is conducted for studying the process which is
      disturbed by white noise to some extent caused by the model, the fermentation
      system and operation fluctuation. EKF shows that calculated results from
      estimated process parameters agree with the experimental results considerably
      better than model prediction without using estimated parameters. Parameter
      analysis gives a better understanding of the kinetics and provides a basis for
      state estimation and state prediction.

PMID- 8155839
TI  - High level expression of Shiga toxin B subunit of Shigella dysenteriae serotype 1
      in Escherichia coli.
AB  - In this study the gene encoding the Shiga toxin (Stx) was cloned from the
      chromosomal DNA of Shigella dysenteriae serotype 1 (W30864). The Stx gene was
      located in a 4.5kb EcoRI fragment. The biological assay revealed that the hybrid
      plasmid pMGC001 containing the Stx gene could produce Shiga toxin. The amount of
      Stx was 16 times more than that produced by its parent. The cloned strain showed
      cytotoxic, entorotoxic and neurotoxic activities. The gene for Stx-B subunit was
      subcloned into a plasmid vector pJLA503 from the plasmid pMGC001. The B subunit
      could be expressed at high level in E. coli and has been purified in large
      quantities. The polyclonal and monoclonal antibodies against B subunit were
      raised. Western blot showed that they could react specifically to the B subunit.

PMID- 8155840
TI  - Sequence analysis of the colonization factor antigen 1 gene of ETEC and
      observation of CFA/1 recombinant clone with electron microscopy.
AB  - The structure gene of the colonization factor antigen 1 (CFA/1) has been
      sequenced. The amino acid sequence of CFA/1 precursor deduced from the nucleotide
      sequence is composed of 170 amino acids. The first 23 amino acids are considered
      to be the signal peptide of the CFA/1 protein. On the basis of the nucleotide
      sequence, three amino acids are different from the protein sequence. Amino acid
      residues at positions 37, 76 and 97 are found to be Ala, Asp and Ser, instead of
      Val, Asn and Ala as determined by amino acid sequencing. The CFA/1 is very
      hydrophobic amino acids. Among the total 170 amino acids, 47% of them are
      hydrophobic amino acids. CFA/1 gene has a typical Shine-Dalgarno sequence and-10
      sequence, but no 35 promoter sequence could be found. The G + C ratio of CFA/1
      gene is 40%. Observation of negatively stained preparations of the culture with
      electron microscopy showed that no fimbriae were found on E. coli C600 strain
      itself, but the cell carrying the plasmid showed thick pili on its surface.

PMID- 8155841
TI  - Combination of DNA single strand synthesis with PCR to construct mung bean
      trypsin inhibitor gene.
AB  - This paper using the synthesis of mung bean trypsin inhibitor gene as an example,
      presented a new method for gene synthesis. The principle of the method was based
      on the combination of the single strand strategy and the PCR technique. The
      synthesis was very simple, convenient and rapid. The mung bean trypsin inhibitor
      is a protein composed of 72 amino acid residues. Its amino acid sequence has been
      determined, but the DNA sequence of gene still unknown. The synthetic mung bean
      trypsin inhibitor gene was 248 bp in length. It contains the encoded sequence,
      the start and stop codons, the restriction sites of EcoRI and BamHI at both ends,
      The codon selection of the synthetic gene was carried out according to the codon
      usage of other plant protease inhibitor gene or plant gene. The synthetic double
      stranded DNA was digested with EcoRI and BamHI or PstI first, then cloned into
      plasmid pUC19. The synthetic gene was proved to be correct by the restriction map
      and the sequence analysis using the dideoxy-mediated chain termination method.

PMID- 8155842
TI  - Kinetic study and modelling on L-arginine fermentation.
AB  - The batch fermentation of L-arginine using Corynebacterium crenatum L-arginine
      producing mutant 971.1 was kinetically studied in a 2.6 L fermentor for the
      following purposes: kinetic classification of L-arginine fermentation by the
      comparison of the two-phases of specific growth rates; modelling of the L
      arginine fermentation, and discussion about the effects of oxygen supply on the
      conversion rate of glucose to L-arginine, by comparing the fraction of glucose
      consumption for L-arginine-formation alpha p and the fraction of glucose
      consumption for cell-growth alpha x under different oxygen transfer coefficients
      kLa. The kinetic fermentative behavior of the strain 971.1 in L-arginine
      formation, which was related to the velocity and effectiveness of the metabolism
      of the cell, was mathematically analyzed.

PMID- 8155845
TI  - Holobionts, hybrids, and cladistic classification.
AB  - David P. Mindell assumes that incorporation of the holobionts (evolutionarily
      stable symbiotic complexes) and hybrids into phylogenetic trees necessarily
      distorts the hierarchical structure of cladistic classification, and must lead to
      reformulation of some basic cladistic concepts (BioSystems, 27, 53-62, 1992). He
      does not regard the Eukarya and Eubacteria as monophyletic taxa, the former being
      'polyphyletic', the latter 'paraphyletic'. We attempt to show that the existence
      of holobionts/hybrids is not a cladistic problem. Cladistics is a systematic
      methodology, not a system of evolutionary hypotheses; cladograms are statements
      about distribution of shared characters (synapomorphies) and, consequently, the
      cladograms are always branching and hierarchically structured. A taxon is
      monophyletic if it has a single root in the cladogram, not a single ancestor 'in
      reality'. Cladistic methodology does not provide a clue for distinguishing
      whether a conflicting distribution of the potential synapomorphies is due to
      reticulation (e.g., symbiogenesis) or convergent evolution. Consequently, both
      Eubacteria and Eukarya either are or are not monophyletic taxa if they are or are
      not determined to be so during cladistic analysis.

PMID- 8155844
TI  - Origins of species: acquired genomes and individuality.
AB  - Entire genomes with their accompanying protein synthetic systems are transferred
      throughout the biosphere primarily as bacteria and protists which become
      symbionts as they irreversibly integrate into pre-existing organisms to form more
      complex individuals. Individualization is stabilized by simultaneous transmission
      of once-separate heterologous genetic systems. The origin of new species is
      hypothesized to correlate with the acquisition, integration and subsequent
      inheritance of such acquired microbial genomes. These processes were recognized
      by Mereschkovsky ("Symbiogenesis" in Russian, 1909) and by Wallin
      ("Symbionticism", see p. 181, this issue).

PMID- 8155843
TI  - Horizontal transfer of ATPase genes--the tree of life becomes a net of life.
AB  - An ancient gene duplication gave rise to the catalytic and non-catalytic subunits
      of each of the three types of proton pumping ATPases: vacuolar, archaebacterial
      and eubacterial. Previously, this gene duplication has been used to root the
      universal tree of life. However, recent findings of archaebacterial type ATPases
      in eubacteria and of eubacterial type in an archaebacterium suggested that both
      types of ATPases may have been already present in the last common ancestor. Here
      we show that a phylogenetic analysis of these ATPase subunits indicates that this
      conclusion is premature. We suggest that horizontal gene transfer can explain the
      data. In addition, we show that the analysis of glutamate dehydrogenases data
      neither affirm nor contradict any particular placement of the last common
      ancestor in the universal tree of life. The prevalence and the mode of horizontal
      gene transfer is discussed.

PMID- 8155846
TI  - Distribution of types of microbial mats at the Ebro Delta, Spain.
AB  - The distribution and types of microbial mats of the Ebro Delta (Catalonia, Spain)
      are described. The studied area is La Banya spit, formed by a narrow sand bar and
      a peninsula, located south of the main body of the Ebro Delta. Sea water can
      penetrate into the back shore through channel inlets, cutting the steeper coastal
      barrier of the open sea side of the spit or through the complex drainage channel
      system of the low-energy beaches in the inner Alfacs Bay. Sea water can stay in
      the back shore almost permanently, trapped in isolated depressions and lagoons.
      The surface distribution of microbial mats in La Banya spit has been studied by
      means of a detailed interpretation of vertical aerial photographs and field work
      consisting of mapping and sampling. The observed different ratios of
      cyanobacteria, as well as the presence and thickness of the layers of anoxygenic
      sulfur phototrophic bacteria, depend on the moisture content, the system
      stability, and the age of the microbial mat. Lyngbya, Oscillatoria, and Spirulina
      are the first cyanobacteria able to colonize the bare sediment. Lyngbya dominates
      in young microbial mats and in mats exposed to frequent desiccation. Microcoleus
      is the second most important colonist in the microbial succession. In relation to
      water, the alternation of emergence and submergence is optimal for the maximal
      development of Microcoleus-dominated microbial mats. We classify the microbial
      mats of the Ebro Delta into five main types: (i) Lyngbya-dominated type, in which
      the anoxygenic phototrophic bacteria are absent and the black layer of sulfate
      reducers is very thin; (ii) Spirulina-dominated type; (iii) Oscillatoria
      dominated type, which is found only at one site and covers a small area--this
      type, like the Spirulina-type mat, is not common in the Ebro Delta; (iv)
      Lyngbya/Microcoleus-transition type, in which Microcoleus and Lyngbya coexist in
      similar proportions--in the more developed mats of this group a layer of purple
      bacteria is usually present, and the black layer of sulfate-reducers is usually
      also well developed; and (v) Microcoleus-dominated type--in La Banya spit, this
      type is found in localities with relatively stable conditions. These areas are
      wet during most of the year. After appropriate conditions of diagenesis, the most
      highly developed microbial mats may be preserved as laminated hard sediments. The
      field study has been completed with cultivation, isolation, and identification of
      the main cyanobacterial genera under laboratory conditions.

PMID- 8155847
TI  - Hypersea and the land ecosystem.
AB  - The land ecosystem, in spite of its relative youth, outstrips the marine
      ecosystem in terms of greater primary productivity and species diversity per unit
      area. This occurs because land eukaryotes actively direct the flow of nutrient
      rich fluids. The body fluids of land eukaryotes have had a significant
      evolutionary and geochemical impact, and we here refer to these fluids, and the
      organisms through which they flow, as 'Hypersea'. Hypersea is a previously
      unrecognized biogeophysical entity formed by eukaryotic life and its symbionts,
      parasites and hyperparasites on land. The oldest convincing evidence for Hypersea
      consists of fossil tracheophytes, mycorrhizal fungi, and protoctists displaying
      intimate ecological interactions in the Lower Devonian Rhynie Chert (approx. 400
      million years old), just older than the first major coal deposits. We use the
      concept of hypermarine upwelling to help explain both (a) the genesis of coal and
      (b) why the average species diversity per unit area and biomass production of the
      land biota has exceeded that of the marine biota for hundreds of millions of
      years.

PMID- 8155848
TI  - Extinction and viruses.
AB  - The micropaleontological record of deep-sea sediments is demonstrably continuous
      through time and, therefore, it can be used to study in detail the evolutionary
      process. Several taxa, including Coccolithophorida, planktic Foraminifera,
      Radiolaria, and diatoms, are abundantly represented. Some species, apparently
      evolved in the marginal marine environment, appear suddenly in the record while
      other species grade into different ones at rates that range from 100,000 years to
      millions of years. The rates are usually different for different morphological
      characters within the same lineage. Every few million years a mass extinction
      occurs--the disappearance of a number of taxa apparently caused by an
      environmental upset of some kind. These events are used by stratigraphers to
      subdivide geologic time. Interspersed between mass extinctions are the background
      extinctions, the individual extinctions of well-established species while the
      sympatric species exhibit no sign of stress. It is hypothesized that background
      extinctions are caused by host-specific viral action. It is further hypothesized
      that background extinctions are a fundamental component of the process of
      evolution.

PMID- 8155849
TI  - The 'tubulin-like' S1 protein of Spirochaeta is a member of the hsp65 stress
      protein family.
AB  - A 65-kDa protein (called S1) from Spirochaeta bajacaliforniensis was identified
      as 'tubulin-like' because it cross-reacted with at least four different antisera
      raised against tubulin and was isolated, with a co-polymerizing 45-kDa protein,
      by warm-cold cycling procedures used to purify tubulin from mammalian brain.
      Furthermore, at least three genera of non-cultivable symbiotic spirochetes
      (Pillotina, Diplocalyx, and Hollandina) that contain conspicuous 24-nm
      cytoplasmic tubules displayed a strong fluorescence in situ when treated with
      polyclonal antisera raised against tubulin. Here we summarize results that lead
      to the conclusion that this 65-kDa protein has no homology to tubulin. S1 is an
      hsp65 stress protein homologue. Hsp65 is a highly immunogenic family of hsp60
      proteins which includes the 65-kDa antigens of Mycobacterium tuberculosis (an
      active component of Freund's complete adjuvant), Borrelia, Treponema, Chlamydia,
      Legionella, and Salmonella. The hsp60s, also known as chaperonins, include E.
      coli GroEL, mitochondrial and chloroplast chaperonins, the pea aphid 'symbionin'
      and many other proteins involved in protein folding and the stress response.

PMID- 8155850
TI  - Surface bacteria of Streblomastix strix are sensory symbionts.
AB  - Streblomastix strix, a protist living in the hindguts of Zootermopsis sp.
      (termites) is covered with pseudomonad-like rod-shaped bacteria. These bacteria
      were demonstrated to be sensory (chemotactic) symbionts for S. strix. S. strix
      moved toward a source of sodium acetate, a presumed food molecule, when its
      bacteria were intact. If the bacteria were removed by antibiotic (carbenecillin)
      treatment, S. strix was unable to orient efficiently in a sodium acetate
      gradient. The mechanism of this interaction was not determined. This is the first
      case documented of a sensory symbiosis involving a surface layer of bacteria.
      However, it may not be an exceptional case given the large numbers of organisms
      with surfaces covered with symbionts. The assays for chemotaxis used in this
      research may be applied in other cases in which motile organisms are covered with
      symbionts.

PMID- 8155851
TI  - Symbionticism in the light of recent cytological investigations--Ivan E. Wallin,
      1969.

PMID- 8155852
TI  - The origin of land plants: a union of alga and fungus advanced by flavonoids?
AB  - This paper addresses the hypothesis that land plants have a biphyletic origin as
      the product of an endocellular mutualism between a green alga and a tip-growing,
      fungus-like organism, culminating in the acquisition of part of the latter's
      genome by the host alga (Atsatt, P.R., 1988, Are vascular plants 'inside-out'
      lichens? Ecology 69, 17-23). According to this hypothesis, the tip-growing
      symbiont's capacity for invasive growth was exploited during the further
      evolution of the holobiont for the development of various specialized plant cell
      types, but especially those displaying tip growth. Here, noting the recent
      discovery of the dependence of pollen tube tip growth on flavonoids, this
      hypothesis is refined and extended by suggesting that a symbiotic relationship
      was advanced by the evolution of UV-protective flavonoids in the alga, followed
      by the evolution of a growth response by the tip-growing symbiont to the presence
      of those flavonoids, allowing the symbiont to continue to live with the alga in
      its new, high-light habitat. This growth response then evolved into a dependence
      on flavonoids in the context of an obligate, mutualistic relationship progressing
      toward endosymbiosis and incorporation of the endocytobiont's genetic capacity
      for cell polarization, tip growth and their control into the host alga's genome.
      Land plants and advanced charophycean algae (which are the closest green-algal
      relatives of land plants) are likely products of this process, while a primitive
      charophycean alga (lacking both tip growth and cell polarization) is proposed to
      have been the likely host for the endocytobiont. A series of tests of this
      hypothesis, based mainly on the identification and molecular phylogenetic
      analysis of appropriate genes, are proposed. Whether the endocytobiont could have
      been a relative of the earliest endomycorrhizal fungi is assessed.

PMID- 8155854
TI  - Sperm competition and the persistence of genes for male homosexuality.
AB  - Homosexuality is increasingly recognized as having a genetic component. Why then
      does it persist, when common sense suggests that it should result in fewer
      offspring? Monozygotic-twin studies permit a rough estimate of the importance of
      genetics (70%) in the development of male homosexuality, and the proportion of
      homosexuals remains constant: Fisher's Theorem then tells us there is an
      advantage to the heterozygote, which we find need be no greater than 2%. Behavior
      and sperm competition suggest what this advantage might be.

PMID- 8155853
TI  - Algal blooms in the spread and persistence of cholera.
AB  - Cholera has been long associated with the seasonality of coastal algal blooms off
      Bangladesh. Using fluorescent antibody (FA) techniques, microbiologists have now
      identified a viable, non-cultivable form of Vibrio cholerae in a wide range of
      marine life, including cyanobacteria (Anabaena variabilis), diatoms (Skeletonema
      costatum), phaeophytes (Ascophyllum nodosum), in copepod molts, and in freshwater
      vascular aquatic plants (water hyacinths and duckweed). In unfavourable
      conditions V. cholerae assumes spore-like forms; with proper nutrients, pH and
      temperature, it reverts to a readily transmissible and infectious state. Nitrates
      and phosphates in sewage and fertilizers cause eutrophication, and scientists
      report an increase in intensity, duration and shifts in the biodiversity of algal
      blooms in many coastal, brackish and fresh waters worldwide. V. cholerae has been
      isolated from phyto- and zooplankton in marine and fresh waters near Lima, Peru.
      V. cholera 01, biotype El Tor, serotype Inaba, may have arrived in the Americas
      in the bilge of a Chinese freighter. There, in the abundant coastal sea life
      along the Latin American Pacific coast, nourished by the Humboldt current and
      eutrophication, it found a reservoir for surviving unfavourable conditions. It is
      hypothesized that the algae and Vibrio populations grew exponentially; consumed
      by fish, mollusks and crustacea, a heavy 'inoculum' of carriers infected with V.
      cholerae was generated and transported into multiple coastal communities.

PMID- 8155855
TI  - Is humanity suicidal?
AB  - The world's fauna and flora has entered a crisis unparalleled since the end of
      the Mesozoic Era, with the extinction rate of species now elevated to more than a
      thousand times that existing before the coming of humanity. Scientists and policy
      makers are ill-prepared to moderate this hemorrhaging, because so little is known
      of the biology of the Earth's millions of species and because so little effort
      has been directed toward conservation thus far. With the vanished species will go
      great potential wealth in scientific knowledge, new products, ecosystems
      services, and part of the natural world in which the human species originated.
      The need for new research and improved management is thus urgent. If it is not
      met, humanity will likely survive, but in a world biologically impoverished for
      all time.

PMID- 8155856
TI  - Gaia: goddess and idea.
AB  - This paper introduces Gaia theory to the general reader. It provides the
      necessary background to follow the development of James Lovelock's thinking as he
      originated the Gaia theory by comparison of the atmospheres around Mars and other
      planets during his sojourn at NASA. Lynn Margulis' contributions to Gaia are also
      presented and the bases for her collaboration with Lovelock explored. In addition
      to descriptions of the discoveries stimulated by Gaia thinking, the paper
      indicates how Gaians have dealt with the controversies that have arisen over the
      theory. Finally, the paper touches on the broader aspects of the Gaia idea.
      Namely, its development into a spiritual elixir, and how it has been a launching
      platform for interdisciplinary thinking inside of and beyond the boundaries of
      the sciences.

PMID- 8155857
TI  - Gaia: goddess or thermostat.
AB  - This is a independent look at the concept of Gaia as a tightly coupled system,
      whose constituents are the biota and the physical environment. Within the system
      the biota, through normal mechanisms of evolution, unwittingly help regulate the
      environment within the bounds necessary for their survival. The example of
      maintaining a broad equilibrium of planetary transpiration is given. Some have
      given Gaia religious or poetical attributes, others see the concept as an
      intellectual tool which contributes to understanding of the relationship between
      animate and inanimate nature.

PMID- 8155858
TI  - Classification of organisms: living and fossil.
AB  - The classification advanced herein provides a framework to which any organism can
      be readily placed and offers comprehensive coverage of the entire biological
      spectrum. The viruses are incorporated as a kingdom of organisms and a rationale
      advanced for a 6-kingdom system. Many seldom-classified fossil organisms are
      included, with a significant number of them classified at an advanced level.
      Individual phyla are recognized for the fossil genera Tribrachidium, Amiskwia,
      Dinomischus, Anomalocaris, Tullimonstrum, Hallucigenia, Opabinia and Pikaia.
      Other seldom-recognized phyla include viruses, conularids, loriciferans,
      tentaculites, hyoliths, scleritophores, myzostomans, acorn worms, conodonts,
      monoblastozoans and volborthellids. The notion that failures (geologically)
      cannot be phyla is rejected. A system of kingdom-related and rank-related
      suffixes is incorporated with the flexible opportunity, if deemed necessary, to
      advance or reduce taxa by re-suffixing. Other features of the complete
      classification of Anderson (Classification of Organisms: Living and Fossil,
      Golden Crowns Press, Lancaster, OH, 1992) include the elimination of duplicate
      taxa, incorporation of geologic ranges and number of species for many groups, and
      extensive usage of common names, which are completely indexed.

PMID- 8155859
TI  - Development of portal vein invasion and its outcome in hepatocellular carcinoma
      treated by transcatheter arterial chemo-embolization.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies in the
      world. One serious complication is the invasion of the portal vein. To
      investigate the new invasion of the portal vein in HCC following treatment by
      transcatheter arterial chemo-embolization (TACE), 124 patients with HCC were
      screened by ultrasound, computed tomography and angiography. Fifteen patients
      were diagnosed with portal vein invasion (PVI) during the initial examination and
      were excluded from the study. Of the remaining 109 patients, 18 developed PVI.
      Fourteen were male and four were female. None of these 18 patients completely
      responded to TACE treatment and all were in recurrence. The median time for
      appearance of PVI after the first TACE was 212 days. The median interval between
      PVI and the last negative ultrasound examination was 100 days. Both were
      correlated with the degree of PVI. The only significant factor affecting the time
      until the appearance of PVI was the TACE treatment. After the development of PVI,
      eight patients continued with the TACE treatment, and three of these patients
      were also treated with portal vein local chemotherapy. The regression of PVI was
      observed in two patients. The median survival time after the discovery of PVI was
      129 days. Factors affecting the survival time were performance state, Pugh
      classification, sex, the area of tumour invasion and continued treatment.

PMID- 8155860
TI  - Association of lymphocytic (microscopic) colitis with tropical sprue.
AB  - Lymphocytic (microscopic) colitis is a disease of unknown aetiology which
      manifests as long-standing intermittent diarrhoea. Diagnosis is confirmed on
      histological examination of the colon. An association of this uncommon disease
      with tropical sprue is described. Tetracycline therapy resulted in a favourable
      clinical response.

PMID- 8155861
TI  - HCV infection and its clinical features in recipients of blood screened for HCV
      (C100-3) antibody.
AB  - After adoption of the anti-hepatitis C virus (C100-3) test, the incidences of
      definite and suspected cases of post-transfusional hepatitis (PTH) were 3.3%
      (7/209) and 7.2% (15/209), respectively. Four patients with definite PTH and
      seven patients with suspected PTH became positive for hepatitis C virus (HCV)
      related antibodies or HCV-RNA after transfusion. These cases that became positive
      for anti-HCV or HCV-RNA showed a peak of alanine aminotransferase (ALT) more than
      4 weeks after operation. Only rare cases that showed ALT peaks within 4 weeks
      after operation became positive for HCV-related antibodies or HCV-RNA. The peak
      ALT levels in cases showing positive conversion tended to be higher than those in
      cases showing no conversion. Judging from these results, cases of suspected PTH
      include those of transient liver disease attributable to surgery as well as clear
      cases of HCV infection. Thus new diagnostic criteria are required including data
      on HCV antibodies or HCV-RNA.

PMID- 8155862
TI  - The effects of dichloroacetate on liver damage and circulating fuels in rats
      exposed to carbon tetrachloride.
AB  - It has been known that carbon tetrachloride-induced liver damage in starved rats
      is ameliorated simply by restoration of feeding. An analogue of dichloroacetate
      has been reported to ameliorate carbon tetrachloride-induced liver damage, and
      dichloroacetate has been shown to have a variety of effects on fuel metabolism.
      We investigated simultaneously the effects of dichloroacetate on liver damage and
      on circulating fuels in rats exposed to carbon tetrachloride. The effects of
      carbon tetrachloride varied with the rat's condition. In starved rats, the liver
      damage was more severe, and serum ketone body concentration decreased. In non
      starved rats, the liver damage was not as severe and the serum ketone body
      concentration increased. The administration of dichloroacetate ameliorated liver
      damage both in starved and in non-starved rats given carbon tetrachloride: the
      administration of dichloroacetate protected from the liver damage particularly in
      starved rats. There were associated changes in the concentrations of circulating
      fuels. When the pyruvate-lowering effect of dichloroacetate was diminished in
      carbon tetrachloride-injected, starved rats, the alanine aminotransferase
      lowering effect of dichloroacetate was also diminished. We propose that
      dichloroacetate's effect on fuel metabolism may produce a hepato-protective
      effect.

PMID- 8155863
TI  - Hepatocellular carcinoma in 13 patients with hepatitis C virus-associated chronic
      hepatitis.
AB  - Thirteen of 81 patients with chronic hepatitis and positive hepatitis C virus
      (HCV) antibody developed hepatocellular carcinoma (HCC) during a follow-up period
      of 54 +/- 38 months. The histopathological findings in HCC-bearing liver in these
      patients included six cases of chronic persistent hepatitis [CPH; mean hepatitis
      activity index (HAI) score: 5.8] and seven cases of chronic aggressive hepatitis
      (CAH) 2A, or 2B (HAI) score: 13.6). Multiple biopsies of the liver in six cases
      revealed that five cases, including four with CPH at the time of HCC diagnosis,
      previously had histopathological findings identical to CAH 2A, and another case
      constantly had CPH during the 8-year follow-up. These findings suggest that HCV
      associated HCC can occur even in patients with HCV antibody positivity and
      inactive or mild chronic hepatitis. This is of interest in the pathogenetic
      mechanisms of HCV-associated HCC.

PMID- 8155864
TI  - Reversibility of organic anion-induced cholestasis: association with compensatory
      hypersecretion of biliary phospholipid and protein in the dog.
AB  - The effect of a concomitant infusion of organic anions, structurally related
      phthaleins, on bile flow was studied in anaesthetized dogs. A combination of rose
      bengal and sulfobromophthalein was found to uniquely and synergistically produce
      an acute, reversible form of intrahepatic cholestasis (< 10% of control level).
      This phenomenon was not observed with the administration of those individual
      organic anions at concentrations previously associated with the induction of
      intrahepatic cholestasis. The infusion of either a micelle forming bile salt,
      sodium taurocholate, or a non-micelle forming bile salt, sodium dehydrocholate,
      rapidly reversed the intrahepatic cholestasis (within 20 min after bile salt
      infusion). During the choleretic phase immediately following the bile salt
      infusion, a transient but marked hypersecretion, a disproportionately increased
      output in relation to that of bile acids, of biliary phospholipid (176% of
      control level by taurocholate and 138% of control level by dehydrocholate), and
      an even more striking amount of biliary protein hypersecretion were observed
      (392% of control level by taurocholate and 357% of control level by
      dehydrocholate). Although the significance of these new post-cholestatic
      observations requires clarification, it is suggested that the intrahepatic
      cholestasis induced by organic anions reflects a reversible defect in the
      mechanism(s) involved in transcellular transport.

PMID- 8155865
TI  - Anti-neutrophil cytoplasmic antibody: a prognostic indicator in primary
      sclerosing cholangitis.
AB  - Considerable variability has been reported in the frequency and specificity of
      anti-neutrophil cytoplasmic antibody with a perinuclear staining pattern (pANCA)
      in patients with chronic liver disease, especially in primary sclerosing
      cholangitis (PSC), and in inflammatory bowel disease. This study examines the
      presence of pANCA in patients with these disorders, in particular those with PSC
      complicated by other biliary disease, and also patients who had undergone
      orthotopic liver transplantation. An indirect immunofluorescent technique was
      used to measure pANCA with serum diluted 1:20. Ten of 39 (26%) patients with PSC
      had detectable pANCA, as did two of nine (22%) with autoimmune chronic active
      hepatitis (AICAH) but none of the 51 patients with other forms of chronic liver
      disease. The presence of pANCA was significantly more frequent in patients who
      had PSC with biliary tract complications, in particular calculi (seven of 16 with
      vs three of 23 without; P = 0.03). Eight of the 12 pANCA-positive patients with
      PSC or AICAH had undergone hepatic transplantation. This was more likely than in
      patients with PSC or AICAH who were pANCA negative (10 of 36; P = 0.02). To date,
      pANCA has been detected after transplantation in four patients with PSC and one
      with AICAH. In patients with PSC or AICAH, pANCA should be sought as a marker of
      prognosis.

PMID- 8155867
TI  - A prospective study of septic complications of endoscopic retrograde
      cholangiopancreatography.
AB  - Prophylactic antibiotics are used in an attempt to avoid the septic complications
      of endoscopic retrograde cholangiopancreatography (ERCP). We prospectively
      performed blood cultures and surveyed patients for complications. The aims were
      first, to determine the incidence of bacteraemia associated with ERCP, second, to
      assess the incidence of clinical sepsis following the procedure and third, to
      evaluate the effectiveness of our antibiotic prophylaxis. One hundred and fifty
      successive patients underwent 179 ERCP. Bacteraemia related to the procedure or
      the underlying pathology was found in nine procedures (5.2%). Bacteraemias were
      more likely to complicate therapeutic procedures (P = 0.015), biliary obstruction
      (P = 0.045) or underlying pathology (P = 0.022). Although 61% of ERCP received
      antibiotics, 22 septic events occurred. Five bacteraemic patients were septic
      despite antibiotics. Septic complications were associated with the same factors
      as bacteraemia. It was concluded that patients with biliary obstruction and
      undergoing therapeutic endoscopic procedures are at greatest risk of bacteraemia.
      Single dose prophylactic antibiotics may not prevent sepsis in these patients and
      longer-acting drugs or repeated dosing may be necessary.

PMID- 8155868
TI  - Glutathione concentrations and glutathione S-transferase activity in human
      colonic neoplasms.
AB  - Tissue concentrations of glutathione (GSH) and the activity of glutathione S
      transferases (GST) are relevant to the inactivation of a variety of xenobiotics
      including carcinogens and anti-neoplastic drugs. In this study, GSH
      concentrations and GST activity were determined in 25 adenomatous polyps removed
      at colonoscopy, and in cancer and uninvolved 'normal' mucosa from 58 operative
      specimens containing colon cancer. We also examined the relationship between GSH
      concentrations, GST activity and rates of cell proliferation as assessed by flow
      cytometry. Concentrations of GSH were significantly higher in adenomas (P =
      0.001) and cancer (P = 0.001) than in uninvolved mucosa while GST activity was
      significantly higher in cancer (P = 0.007). There was a positive relationship
      between GSH concentrations and GST activity in adenomas (P = 0.001) but not in
      uninvolved mucosa (P = 0.06) or cancer (P = 0.4). Concentrations of GSH and GST
      activity were independent of results from flow cytometry. The higher
      concentrations of GSH in colonic neoplasms and the raised activity of GST in
      cancer may contribute to their resistance to anti-neoplastic drugs.

PMID- 8155866
TI  - Histopathology of portal tracts in livers after transcatheter arterial chemo
      embolization therapy for hepatocellular carcinoma.
AB  - To study the influence of transcatheter arterial embolization therapy (TAE) on
      the portal tracts, 32 cases of hepatocellular carcinoma (HCC) with a history of
      TAE were examined. Portal tract elements are said to be mainly supplied by
      hepatic arterial blood, as is HCC. The following changes were found: peribile
      duct fibrosis; biliary epithelial injuries; bile duct necrosis; fibrous
      thickening of the intima and adventitia of arteries; thrombosis or stenosis of
      portal vein branches; and fibrosis of portal tract itself. We failed to correlate
      these histopathologic changes with the frequency of TAE or the interval between
      TAE therapy and surgery or autopsy. Semi-quantitative assessment disclosed that
      vessels of the peribiliary vascular plexus (PVP) which are known to be derived
      from hepatic arterial branches, were considerably decreased. There was little
      correlation between the degree of reduction of PVP and the observed
      histopathologic changes of portal tracts. It is suggested that TAE causes adverse
      effects on the elements of portal tracts and a reduction in the PVP in the
      vicinity of HCC, but the relationship between them is unclear.

PMID- 8155870
TI  - Endoscopic haemostasis for gastrointestinal bleeding: the dawning of a new era.

PMID- 8155869
TI  - Limitations of endoscopic haemostasis by ethanol injection and surgical
      management for bleeding peptic ulcer.
AB  - Two hundred and fifty-three patients with bleeding peptic ulcer underwent
      therapeutic endoscopy using local ethanol injection and were evaluated to
      determine the need for surgery and outcome. Permanent endoscopic haemostasis was
      achieved in 178 (70.4%) cases. Pulsatile arterial bleeding in ulcers and shock on
      admission (respectively, P < 0.01, P < 0.05) were significantly more frequent in
      patients with unsuccessful endoscopic treatment. Postoperative stay was
      significantly longer (P < 0.05) for patients with bleeding peptic ulcer than for
      patients requiring surgery for intractable ulcer without bleeding. Surgery was
      recommended if three attempts at endoscopic treatment did not achieve permanent
      haemostasis. The need for more than three such treatment sessions and the
      presence of a large excavated ulcer with an exposed vessel in an elderly patient
      were considered to indicate the necessity for surgery. Surgical procedures to
      which the operator is accustomed and intensive management were recommended for
      emergency cases to optimize the likelihood of survival.

PMID- 8155872
TI  - Intrahepatic peribiliary glands of humans. I. Anatomy, development and presumed
      functions.
AB  - The intrahepatic biliary tree is regarded as an excretory duct of two secretory
      units: hepatocytes and intrahepatic peribiliary glands. This review describes the
      anatomy, development and presumed functions of the latter. These glands are
      preferentially located around the intrahepatic large bile ducts, and are
      histologically divided into intramural and extramural structures. The former
      consist of simple tubular glands with much mucin, and are sparsely and
      irregularly distributed within the ductal wall. The latter are characterized by
      the presence of excretory units that consist of seromucinous acini and a
      conducting system in the periductal tissue. Pancreatic exocrine acini are
      occasionally admixed with extramural glands. These peribiliary glands appear in
      the late fetal period and complete their development about 15 years after birth.
      Extramural and intramural glands secrete neutral and acid mucin into the ductal
      lumen. Extramural glands contain several enzymes for digestion of protein and
      lipids. Neural and vascular supply of these glands may be related to the
      regulation of their secretion. Specific and non-specific immune responses within
      this glandular system may also be essential in the sterility of bile.

PMID- 8155871
TI  - Immunoreactivity to M2 proteins in antimitochondrial antibody-negative patients
      with primary biliary cirrhosis.
AB  - Although antimitochondrial auto-antibodies are characteristically present in the
      serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy
      between the positivity for antimitochondrial antibody (AMA) and that for anti-M2
      auto-antibody. In an attempt to explain the discrepancy, this study investigates
      the relationship between the AMA titre, determined by indirect
      immunofluorescence, and immunoreactivity to four inner mitochondrial membrane
      proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129
      patients with PBC. Antimitochondrial antibody positivity was identified in 114
      (88%) of 129 patients with clinically and histologically confirmed PBC. There
      were no significant differences between the AMA-negative and AMA-positive groups
      in clinical characteristics or histologically determined disease stage.
      Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one
      or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had
      antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of
      the 64 patients with high AMA titres (> or = 1:320) had antibodies to all four M2
      proteins. There was a significant rank correlation between the AMA titre and the
      number of antibodies to M2 proteins (P < 0.01). These findings indicate that the
      AMA titre is not influenced by the immunogenicity of M2 proteins but by the
      number of M2 proteins that elicit an antibody response and that decreased
      immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.

PMID- 8155873
TI  - Intrahepatic peribiliary glands of humans. II. Pathological spectrum.
AB  - The pathological spectrum of intrahepatic peribiliary glands is reviewed here.
      Several categories of histopathological changes such as necro-inflammation,
      cystic dilatation, hyperplasia and neoplasia have been identified in this
      glandular system. Necro-inflammation is associated with biliary tract diseases
      and chronic advanced liver diseases and may also appear in the livers of subjects
      with extrahepatic diseases such as sepsis. Cystic changes of microscopic sizes
      are not uncommon in autopsy livers of chronic advanced liver diseases, portal
      hypertensive diseases and also polycystic liver of adult type. Grossly
      recognizable cysts are, however, infrequent and occasionally cause compression of
      the adjoining bile ducts. Hyperplasia of these glands, which occurs consistently
      in hepatolithiasis and more variably in other conditions (e.g. biliary tract
      infection and submassive hepatic necrosis), may be associated with hypersecretion
      of seromucinous substances. Hyperplasia of peribiliary glands may then lead to
      mucin-related biliary diseases. In addition, these glands, particularly the
      hyperplastic ones, could be a precursor of cholangiocarcinoma. The pathological
      spectrum of the intrahepatic peribiliary glands is being expanded, although a
      clinical pathological correlation remains uncharted. Furthermore, age-related
      variations and non-specific reactive changes of these glands remain unexplored.

PMID- 8155874
TI  - Pathogenesis of pigment stones and medical treatment.

PMID- 8155875
TI  - Type C chronic hepatitis associated with thrombocytopenia in two patients.
AB  - Portal hypertension in the presence of chronic hepatitis is generally thought to
      develop during the progression of the chronic hepatitis to cirrhosis. Before the
      establishment of assays for diagnosing hepatitis C virus infection, such a case
      of portal hypertension without liver cirrhosis could be misdiagnosed as
      idiopathic portal hypertension. It had not fully determined whether portal
      hypertension might precede the onset of cirrhosis in type C chronic hepatitis.
      This report presents two cases of women with chronic hepatitis C who developed
      severe thrombocytopenia; each showed splenomegaly and hypersplenism due to portal
      hypertension. Angiographic study and histological analysis were conducted to
      determine the cause of the portal hypertension. Histological evaluation showed an
      intrahepatic presinusoidal block pattern and fibrotic changes in the periportal
      area, but no evidence of liver cirrhosis or of other incidental complications
      such as idiopathic portal hypertension. Both of these patients exhibited normal
      platelet counts after splenectomy. Thus, type C chronic hepatitis can lead to
      portal hypertension, as demonstrated in these two patients.

PMID- 8155877
TI  - Regulation of the rab17 gene promoter in transgenic Arabidopsis wild-type, ABA
      deficient and ABA-insensitive mutants.
AB  - The abscisic acid-responsive gene rab17 is induced during maize embryo maturation
      and in vegetative tissues under water stress conditions. To investigate how ABA
      is involved in the induction of the rab17 gene, we present here a genetic
      approach to analyse the transcriptional regulation of the 1.3 kb rab17 promoter
      fragment in transgenic wild-type Arabidopsis and mutants which are deficient
      (aba) and insensitive (abi1, abi2 and abi3) to ABA. During seed development the
      rab17 promoter fragment confers similar temporal and spatial regulation on the
      reporter gene GUS, both in transgenic wild-type and ABA-deficient and ABA
      insensitive mutants. The rab17 promoter was only active in embryo and endosperm
      during late seed development, although the ABA-deficient embryo mutant showed a
      reduction in the level of GUS activity. During germination rab17 promoter
      activity decreases, and GUS activity is not enhanced by water stress in
      transgenic wild-type and mutant plants. In contrast, transcription of the
      Arabidopsis endogenous rab gene is stimulated by water stress, both in wild-type
      and ABA-insensitive mutants. Our data suggest that different molecular mechanisms
      mediate seed-specific expression and ABA water stress induction of the rab17 gene
      and indicate strong conservation of the seed-specific regulatory mechanism for
      rab genes in monocot and dicot plants.

PMID- 8155878
TI  - The S11 and S13 self incompatibility alleles in Solanum chacoense Bitt. are
      remarkably similar.
AB  - A genomic clone of the S11 allele from the self-incompatibility locus (S locus)
      in Solanum chacoense Bitt. has been isolated by cross-hybridization to the S.
      chacoense S13 allele and sequenced. The sequence of the S11 allele contains all
      the features expected for S genes of the Solanaceae, and S11 expression, as
      assessed by northern blots and RNA-PCR, was similar to that of other S. chacoense
      S alleles. The S11 protein sequence shares 95% identity with the phenotypically
      distinct S13 protein of S. chacoense and is the gametophytic S allele with the
      highest similarity to an existing allele so far discovered. Only 10 amino acid
      changes differentiate the mature proteins from these two alleles, which sets a
      new lower limit to the number of changes that can produce an altered S allele
      specificity. The amino acid substitutions are not clustered, suggesting that an
      accumulation of random point mutations can generate S allele diversity. The S11
      intron is unusual in that it could be translated in frame with the coding
      sequence, thus suggesting an additional mechanism for the generation of new S
      alleles.

PMID- 8155876
TI  - Structure and regulation of an ABA- and desiccation-responsive gene from the
      resurrection plant Craterostigma plantagineum.
AB  - A gene from the resurrection plant Craterostigma plantagineum (CDeT6-19) encoding
      a protein with sequence similarity to a major group of late embryogenesis
      abundant proteins (termed rab17, dehydrin or Lea D11) is regulated by abscisic
      acid (ABA) and desiccation. The corresponding transcript and protein is highly
      inducible in vegetative and callus tissue. To analyse the mechanism of CDeT6-19
      regulation its promoter was fused to the beta-glucuronidase reporter gene (GUS)
      and introduced by PEG (polyethylene glycol) into protoplasts of Craterostigma or
      tobacco. With 889 bp of promoter sequence the GUS expression was significantly
      stimulated by ABA treatment in transient expression assays. ABA responsiveness
      was still observed with shorter promoter fragments, although they gave rise to
      lower GUS activities. Sequence comparisons with promoters from related genes of
      other species identified the conservation of potential ABA-responsive elements.
      In tobacco and Craterostigma plants stably transformed with CDeT6-19 promoter
      constructs a basal GUS activity is observed. However, GUS expression is enhanced
      by ABA or drying treatment of leaf tissues. In tobacco high promoter activity was
      observed in mature seeds (embryos) and in pollen.

PMID- 8155879
TI  - Conserved gene clusters in the highly rearranged chloroplast genomes of
      Chlamydomonas moewusii and Chlamydomonas reinhardtii.
AB  - We have extended to about 75 the number of genes mapped on the Chlamydomonas
      moewusii and Chlamydomonas reinhardtii chloroplast DNAs (cpDNAs) by partial
      sequencing of the very closely related C. eugametos and C. moewusii cpDNAs and by
      hybridizations with Chlamydomonas chloroplast gene-specific sequences. Only four
      of these genes (tscA and three reading frames) have not been identified in any
      other algal cpDNAs and thus may be specific to Chlamydomonas. Although the C.
      moewusii and C. reinhardtii cpDNAs differ by complex sequence rearrangements, 38
      genes scattered throughout the genome define 12 conserved clusters of closely
      linked loci. Aside from the rRNA operon, four of these gene clusters share
      similarity to evolutionarily primitive operons found in other cpDNAs,
      representing in fact remnants of these operons. Our results thus indicate that
      most of the ancestral bacterial operons that characterize the chloroplast genome
      organization of land plants and early-diverging photosynthetic eukaryotes have
      been disrupted before the emergence of the polyphyletic genus Chlamydomonas. All
      gene rearrangements between the C. moewusii and C. reinhardtii cpDNAs, with the
      exception of those accounting for the relocations of atpA, psbI and rbcL,
      occurred within corresponding regions of the genome. One of these rearrangements
      seems to have led to disruption of the ancestral region containing rpl23, rpl2,
      rps19, rpl16, rpl14, rpl5, rps8 and the psaA exon 1. This gene cluster, which
      bears striking similarity to the Escherichia coli S10 and spc operons, spans a
      continuous DNA segment in C. reinhardtii, while it maps to two separate fragments
      in C. moewusii.

PMID- 8155880
TI  - Cloning of two gibberellin-regulated cDNAs from Arabidopsis thaliana by
      subtractive hybridization: expression of the tonoplast water channel, gamma-TIP,
      is increased by GA3.
AB  - The Arabidopsis ga1 mutant has very low levels of endogenous, active gibberellins
      and thus has an extreme dwarf phenotype; application of GA3 induces stem
      elongation and flower development. To test the hypothesis that GA action in this
      system involves changes in gene expression, we have cloned mRNAs whose abundance
      changes following GA application. A subtraction cloning scheme for the isolation
      of differentially regulated cDNAs was established, involving hybridization of
      single-stranded cDNA to biotinylated mRNA. cDNA populations enriched up to 150
      fold in GA-regulated sequences were produced and cDNA libraries generated.
      Screening of these libraries has isolated two clones that identify mRNAs of ca.
      1100 and 750 bases whose abundance is markedly increased 24 h after GA
      application. One of these clones encodes the vegetative form of the Arabidopsis
      tonoplast intrinsic protein (gamma-TIP), a water channel protein, the expression
      of which has recently been shown to be correlated with regions of cell expansion.
      The second clone is expressed only in the inflorescence and encodes a proline-
      and glycine-rich protein that may be a cell wall component.

PMID- 8155881
TI  - Structure and light-regulated expression of the gsa gene encoding the chlorophyll
      biosynthetic enzyme, glutamate 1-semialdehyde aminotransferase, in Chlamydomonas
      reinhardtii.
AB  - The gsa gene, which encodes glutamate 1-semialdehyde (GSA) aminotransferase
      (GSAT), an enzyme in the chlorophyll and heme biosynthetic pathway, has been
      cloned from Chlamydomonas reinhardtii by complementation of an Escherichia coli
      hemL mutant. The deduced C. reinhardtii GSAT amino acid sequence has a high
      degree of similarity to GSAT sequences from barley, tobacco, soybean and various
      prokaryotic sources. In vitro enzyme activity assays from E. coli transformed
      with the C. reinhardtii GSAT cDNA showed that higher levels of GSAT activity are
      associated with the expression of the cDNA insert. Analysis of changes in mRNA
      levels in light:dark synchronized C. reinhardtii cultures was done by northern
      blotting. The level of GSAT mRNA nearly doubled during the first 0.5 h in the
      light and increased over 26-fold after 2 h in the light. This increase is
      comparable to previously reported increases in GSAT activity in dark-grown
      cultures transferred to the light, and is the first report of induction by light
      of a gene encoding an ALA biosynthetic enzyme in plant or algal cells. The
      accumulation of GSAT mRNA follows the pattern of chlorophyll accumulation and the
      pattern of chlorophyll a/b-binding protein (cabII-1) mRNA accumulation in these
      cells, suggesting that the two genes may be regulated by light through a common
      mechanism. Additional evidence that the GSAT mRNA may be transcriptionally
      regulated by light is found in the genomic sequence of the gsa gene.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155883
TI  - Identification of conserved domains in the delta 12 desaturases of cyanobacteria.
AB  - Cyanobacterial genes for enzymes that desaturate fatty acids at the delta 12
      position, designated desA, were isolated from Synechocystis PCC6714,
      Synechococcus PCC7002 and Anabaena variabilis by cross-hybridization with a DNA
      probe derived from the desA gene of Synechocystis PCC6803. The genes of
      Synechocystis PCC6714, Synechococcus PCC7002 and A. variabilis encode proteins of
      349, 347 and 350 amino acid residues, respectively. The transformation of
      Synechococcus PCC7942 with the desA genes from Synechocystis PCC6714,
      Synechococcus PCC7002 and A. variabilis was associated with the ability to
      introduce a second double bond at the delta 12 position of fatty acids. The amino
      acid sequence of the products of the desA genes revealed the presence of four
      conserved domains. Since one of the conserved domains was also found in the amino
      acid sequences of omega 3 desaturases of Brassica napus and mung bean, this
      domain may play an essential role in the introduction of a double bond into fatty
      acids bound to membrane lipids.

PMID- 8155888
TI  - Speech recognition in recurrent otitis media: results in a set of identical
      twins.
AB  - Performance-intensity functions for Pediatric Speech Intelligibility Test (PSI)
      word and sentence materials presented in competition were obtained for a set of
      identical female twins, aged 4 years, 2 months. Twin B had a medical history
      significant for recurrent otitis media, while Twin A had only one reported
      occurrence of the disease. Twin A yielded normal functions for both word and
      sentence materials. Twin B, however, yielded an essentially normal function for
      sentences, but the function for monosyllabic words was grossly depressed. These
      findings support the hypothesis that transient conductive hearing loss and
      auditory deprivation resulting from recurrent otitis media can affect the
      processing of phonetic information essential to the development of word
      recognition skills.

PMID- 8155889
TI  - Acoustic reflex threshold tenth percentiles and functional hearing impairment.
AB  - This study addressed the issue of whether functional impairments can be
      identified or confirmed using tonal acoustic reflex thresholds (ARTs). Tonal ARTs
      from 74 ears with functional impairments were compared to 10th percentiles of the
      ARTs for normal and cochlear-impaired ears at 500 to 2000 Hz (Gelfand, Schwander,
      and Silman, 1990). Only one ear (5.3%) was correctly identified among the 19 ears
      in which all of the voluntary thresholds at 500 to 2000 Hz were < or = 55 dB HL.
      Acoustic reflex thresholds correctly identified functional losses in 70.9
      percent, 78.6 percent, and 85.7 percent of the ears with voluntary thresholds >
      or = 60 dB HL at one, two, or three of these frequencies, respectively. The false
      positive rate was only 5 to 7 percent for a control group of 50 ears with genuine
      sensorineural hearing losses. The results indicate that tonal ARTs are an
      effective nonbehavioral tool for identifying or substantiating the presence of
      functional losses when thresholds are > or = 60 dB HL; however, ARTs cannot
      identify functional components when thresholds are < or = 55 dB HL.

PMID- 8155882
TI  - Truncated presequences of mitochondrial F1-ATPase beta subunit from Nicotiana
      plumbaginifolia transport CAT and GUS proteins into mitochondria of transgenic
      tobacco.
AB  - The mitochondrial F1-ATPase beta subunit (ATPase-beta) of Nicotiana
      plumbaginifolia is nucleus-encoded as a precursor containing an NH2-terminal
      extension. By sequencing the mature N. tabacum ATPase-beta, we determined the
      length of the presequence, viz. 54 residues. To define the essential regions of
      this presequence, we produced a series of 3' deletions in the sequence coding for
      the 90 NH2-terminal residues of ATPase-beta. The truncated sequences were fused
      with the chloramphenicol acetyl transferase (cat) and beta-glucuronidase (gus)
      genes and introduced into tobacco plants. From the observed distribution of CAT
      and GUS activity in the plant cells, we conclude that the first 23 amino-acid
      residues of ATPase-beta remain capable of specifically targeting reporter
      proteins into mitochondria. Immunodetection in transgenic plants and in vitro
      import experiments with various CAT fusion proteins show that the precursors are
      processed at the expected cleavage site but also at a cryptic site located in the
      linker region between the presequence and the first methionine of native CAT.

PMID- 8155885
TI  - Gene isolation through genomic complementation using an indexed library of
      Chlamydomonas reinhardtii DNA.
AB  - Hundreds of mutants with defects in a variety of physiologically important
      functions, such as photosynthesis, respiration, flagellar motility, phototaxis,
      circadian rhythms and the cell cycle, have been isolated from cultures of
      Chlamydomonas reinhardtii. In only a few cases have the genes responsible for
      these mutations been cloned and sequenced. The development of efficient methods
      for transformation with nuclear genes [7] has allowed the recent demonstration of
      gene isolation through genomic complementation with a pooled library of C.
      reinhardtii DNA [9]. To improve the efficiency with which genes complementing a
      particular mutation can be isolated, we have established an indexed (ordered)
      cosmid library of 11,280 individual clones contained in the separate wells of 120
      microtiter plates. The average insert size is ca. 38 kb. PCR analysis of five
      sequenced nuclear genes present in the Chlamydomonas library revealed a range
      from two copies for the alpha 2- and beta 2-tubulin genes to at least seven
      copies for the argininosuccinate lyase gene. Overall, these five clones were
      represented an average of > or = 3.4 times in the library. Thus, the probability
      that any one particular nuclear gene of < 1000 bp will be found in the library is
      > or = 97%, and the probability that a gene of ca. 10,000 bp will be found in the
      library is ca. 92%. Rapid screening methods with cosmid DNAs pooled from
      individual microtiter dishes have been applied successfully. Bacteria containing
      clones of the argininosuccinate lyase gene have been identified through genomic
      complementation of a Chlamydomonas mutant bearing an inactive argininosuccinate
      lyase gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155891
TI  - Human summating potential to tone bursts: observations on tympanic membrane
      versus promontory recordings in the same patients.
AB  - Electrocochleographic responses to tone bursts and clicks were recorded from the
      tympanic membranes (TMs) and promontories of six suspected Meniere's patients.
      Although the majority of ears had normal summating potentials (SPs), regardless
      of recording site and stimulus type, some displayed amplitude-enlarged SPs at
      both sites and to both types of stimuli. The following observations were made
      from these patients regarding the choice of recording approaches and stimuli for
      ECochG: (1) Although SP amplitudes at the promontory were approximately four
      times larger than corresponding TM values, response "patterns" leading to
      diagnostic interpretation were the same at both sites; (2) the majority of
      patients who displayed enlarged SP amplitudes to tone bursts also had enlarged
      SPs to clicks; and (3) with tone-burst stimuli, the amplitude of the SP alone was
      sufficient for diagnostic interpretation of the ECochG waveform.

PMID- 8155890
TI  - Normal summating potential to tone bursts recorded from the tympanic membrane in
      humans.
AB  - The use of tone-burst stimuli for electrocochleography (ECochG) may offer certain
      advantages over conventional broad-band clicks. Namely, the summating potential
      (SP) component can be examined at different frequencies and may be easier to
      define and measure. To apply these findings clinically, it would first be
      necessary to establish SP amplitudes as a function of tone-burst frequency in
      normal listeners. The purpose of the present study was to do this using the
      tympanic membrane (TM) as the primary ECochG recording site. ECochG was recorded
      from 20 normal ears. Stimuli included 500-, 1000-, 2000-, 4000-, and 8000-Hz tone
      bursts presented randomly at 90 dB nHL. Mean SP amplitudes at these frequencies
      were +0.19, +0.17, +0.08, +0.10, and +0.22 microvolts, respectively. Although
      mean amplitudes were slightly positive regarding baseline, individual amplitudes
      varied between -0.41 and +0.73 microvolts. This study offers additional evidence
      that the SP to tone bursts can be recorded from the TM. The normative data
      provided should be useful for extended studies involving clinical populations.

PMID- 8155887
TI  - A homologue of the 65 kDa regulatory subunit of protein phosphatase 2A in early
      pea (Pisum sativum L.) embryos.
AB  - A partial cDNA, isolated from an early developing pea (Pisum sativum L.) embryo
      library, was found to encode a plant homologue of the regulatory subunit (PR65)
      of protein phosphatase 2A (PP2A). Comparison of the deduced amino acid sequence
      with a human PR65 sequence showed that the regulatory subunit of PP2A has been
      highly conserved during evolution. Southern analysis demonstrated that in pea and
      rape the catalytic and regulatory subunits of PP2A are encoded by multigene
      families. The levels of the transcripts encoding each subunit are developmentally
      regulated during pea embryogenesis and expression of the regulatory subunit is
      not solely restricted to the embryo.

PMID- 8155886
TI  - Nucleotide sequence of a cDNA clone encoding the precursor of the peridinin
      chlorophyll a-binding protein from the dinoflagellate Symbiodinium sp.
AB  - mRNA from the dinoflagellate Symbiodinium sp. isolated from the staghorn coral
      Acropora formosa was used for the construction of cDNA libraries. A cDNA clone
      was identified which encoded the precursor of peridinin-chlorophyll a-binding
      protein (PCP), including a 52 amino acid transit peptide and the 313 amino acid
      mature protein. The deduced amino acid sequence clearly contains an internal
      duplication, implying that amongst dinoflagellates the M(r) 35,000 form of PCP
      has arisen by duplication and fusion of genes encoding the M(r) 15,000 form. This
      is the first reported sequence of a dinoflagellate light-harvesting protein. The
      anatomy of the mature protein and the transit peptide are discussed.

PMID- 8155893
TI  - Health and Nutrition Examination Survey of 1971-75: Part II. Tinnitus, subjective
      hearing loss, and well-being.
AB  - The Health and Nutrition Examination Survey of 1971-75 contains valuable
      information because it provides unbiased estimates of the state of hearing in the
      general population. Here, three facets of the subjective aspects of hearing loss
      are examined: frequent and bothersome tinnitus, ratings of hearing, and general
      well-being. The period prevalence of frequent, bothersome tinnitus varied with
      race and gender (13 to 17%) with higher rates among blacks and females. The mean
      air-conduction thresholds (0.5 to 4 kHz) of those reporting frequent and
      bothersome tinnitus did not exceed 32 dB HL. Mean audiograms associated with
      those who rated both ears good, fair, poor, or deaf were significantly different
      from each other. Mean poorer ear audiograms for those rating one ear as good were
      significantly better than those for comparable symmetrical ratings. Last, there
      was no clear, consistent relationship between audiometric thresholds and measures
      of well-being.

PMID- 8155884
TI  - Homologues of wheat ubiquitin-conjugating enzymes--TaUBC1 and TaUBC4 are encoded
      by small multigene families in Arabidopsis thaliana.
AB  - Covalent attachment of ubiquitin to other cellular proteins has been implicated
      in a multitude of diverse physiological processes in eukaryotes including
      selective protein degradation. This attachment is carried out by a multi-enzyme
      pathway consisting of three classes of enzymes: ubiquitin-activating enzymes
      (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin-protein ligases (E3s).
      E2s accept activated ubiquitin from E1 and conjugate it to target proteins with
      or without the participation of specific E3s. Previously, we have isolated wheat
      cDNAs encoding 16 and 23 kDa E2s, TaUBC1 and TaUBC4, respectively. TaUBC1 shows
      structural homology to the yeast RAD6 E2 that is essential for DNA repair whereas
      TaUBC4 is related to the yeast ScUBC8 E2, both of which effectively conjugate
      ubiquitin to histones in vitro but as yet are without a known in vivo function.
      Here, we report the isolation of genomic and cDNA homologues of these genes from
      Arabidopsis thaliana. In Arabidopsis, both of these E2s are encoded by three
      member gene families. Members of the AtUBC1 gene family, comprising AtUBC1, 2 and
      3, encode 150-152 amino acid proteins that are 83-99% identical to each other and
      TaUBC1 and contain four introns that are conserved with respect to position.
      Members of the AtUBC4 gene family, comprising AtUBC4, 5 and 6, encode 187-191
      amino acid proteins that are 73-88% identical to each other and TaUBC4 and
      contain five introns that are conserved with respect to position.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155894
TI  - Maximum usable real-ear insertion gain with ten earmold designs.
AB  - The present study compared the maximum usable real-ear insertion gain (REIG)
      permitted by 10 earmold designs that varied in the amount of occlusion. These
      earmolds were coupled to a high-gain hearing aid (Phonak Super-Front PPCL). In
      addition, the specificity of a nonoccluding earmold for the Oticon E43 hearing
      aid was examined. Maximum usable REIG, defined as the insertion gain obtained
      with the hearing aid set to just below the point of acoustic feedback after jaw
      movement, was determined in 10 hearing-impaired subjects. The results showed that
      earmold style had a significant effect on the magnitude of maximum REIG. Among
      the occluding earmolds, no difference in REIG was noted among the shell, canal,
      and skeleton earmolds, while the standard earmold permitted the least amount of
      maximum REIG. For the nonoccluding earmolds, those that were more occluding
      permitted greater REIG than those that were less occluding. The amount of
      occlusion on a nonoccluding earmold affected the maximum REIG provided by the
      Oticon E43 hearing aid.

PMID- 8155892
TI  - Health and Nutrition Examination Survey of 1971-75: Part I. Ear and race effects
      in hearing.
AB  - The Health and Nutrition Examination Survey of 1971-75 contains unique hearing
      data because its design permits generalization to noninstitutionalized civilians
      in the continental United States. Air-conduction thresholds and their
      relationships to age, ear, gender, frequency, and race were examined in
      unscreened 25- to 74-year-olds. Although the observed effects of age, gender, and
      frequency were expected, three aspects of the results were remarkable. First,
      there was support for previous observations that older females have poorer low
      frequency hearing. Second, there was an ear effect among white males who had
      poorer 2 and 4 kHz mean thresholds on the left at all ages. Third, there was a
      pattern of poorer mean thresholds for blacks that was particularly evident in
      comparisons between black and white females.

PMID- 8155896
TI  - Hearing loss from a bicycle horn.
AB  - A 39-month-old child with previously documented normal hearing suffered acoustic
      trauma from a bicycle horn activated at his ear. Six days after the insult, a
      4000-Hz 50-dB sensorineural hearing loss was found. This threshold improved to 30
      dB HL over 6 months. The horn produces 143 dB peak SPL, a level clearly
      associated with a high risk for hair cell damage. This case shows the need for
      regulations limiting sound levels or requiring warning labels on potentially
      damaging toys and other recreational devices. Had a warning been provided, the
      parents of this child would not have bought the horn as a toy.

PMID- 8155895
TI  - Communication strategies of adult cochlear implant candidates.
AB  - Adult cochlear implant candidates' abilities to cope with communication breakdown
      were assessed using the Communication Strategies Task (CST). Forty adult cochlear
      implant candidates with acquired hearing losses and 10 adults with normal hearing
      served as subjects. Appropriateness of responses to the CST were rated by 10
      certified speech-language pathologists and audiologists. Seventy-six percent of
      the subjects demonstrated difficulty identifying onset or resolution of
      communication breakdown, communicators' feelings, factors contributing to
      communication breakdown, and appropriate repair strategies. The responses of
      individuals with sudden hearing losses did not differ significantly from the
      responses of individuals with progressive hearing losses. Response patterns did
      not correlate with the age of onset of the hearing loss, duration of deafness,
      age at the time of evaluation, or educational background. The results of this
      study suggest that ability to cope with communication breakdown must be evaluated
      on an individual basis.

PMID- 8155897
TI  - Concurrently recorded auditory event-related potentials and behavioral responses
      to dichotic CV stimuli.
AB  - Auditory event-related potentials (AERPs) were recorded concurrently with
      behavioral responses to dichotic CVs in 16 young, normal, right-handed, female
      subjects. The results showed the expected behavioral right-ear advantage and an
      N105-P184 complex of significantly greater amplitude over the left temporal
      region than over the right. In another normal individual showing a consistent
      behavioral left-ear advantage, we found differences in AERP amplitude and
      morphology favoring right-hemispheric lateralization for speech.

PMID- 8155898
TI  - Matrix-assisted laser desorption/ionization of restriction enzyme-digested DNA.
AB  - Matrix-assisted laser desorption/ionization, by a time-of-flight mass
      spectrometer, has been successfully used for detection of restriction enzyme
      digested DNA. However, the oligonucleotide segments detected correspond to the
      molecular weights of single strands.

PMID- 8155899
TI  - Study of anticancer drug interaction with DNA by means of particle-induced
      desorption mass spectrometry: prospydine and deoxyguanosine-5'-monophosphate.
AB  - Using 252CF particle desorption mass spectrometry, the interaction between an
      antitumour drug prospydine (Pro) and deoxyguanosine-5'-monophosphate (pdG) has
      been studied. The adduct which corresponds to a peak at m/z 524.5 and which
      occurs as a result of the particular degradation of Pro during its alkylating of
      pdG has been found.

PMID- 8155902
TI  - The granular convoluted tubule (GCT) cell of rodent submandibular glands.
AB  - The granular convoluted tubule (GCT) is a segment of the duct system of all
      rodents, situated between the striated and intercalated ducts. It has the
      peculiar property of synthesizing a large variety of biologically active
      polypeptides whose role in saliva remains unknown. The literature on the fine
      structure of GCT cells is critically reviewed. Some recent developments on
      endocrine regulation of the structure and contents of rodent GCT cells are
      summarized, with emphasis on EGF, NGF, renin, and kallikrein proteases. A survey
      of the distribution of GCT cells in several vertebrate families is presented.

PMID- 8155900
TI  - Observation of large multimers in the electrospray ionization mass spectrometry
      of peptides.
AB  - Large multimeric ions were detected from electrospray ionization (ESI) mass
      spectrometry of peptides, using a quadrupole mass spectrometer of standard mass
      range. Multimers, up to heptamers, were seen for angiotensin I; and multimers, up
      to pentamers, were observed for renin substrate. The appearance of the multimeric
      species could be controlled by manipulation of sampling conditions in the ESI
      interface. The relevance of the observation of large multimers to proposed
      mechanisms of ESI is discussed. Implications of the observation of large
      multimers to efforts to deduce higher order structure of biomolecules from ESI
      mass spectrometric experiments are also noted.

PMID- 8155901
TI  - Characterization of glucuronic acid conjugates of a novel angiotensin receptor
      antagonist.
AB  - Nanogram quantities of glucuronic acid conjugates of GR117289 in rat and dog bile
      have been analysed by semi-microbore high-performance liquid chromatography
      (HPLC)/ionspray mass spectrometry with on-line UV diode array detection. The
      determination of drug metabolites in bile has often proved problematical due to
      the large number of endogenous components in this biological matrix, in
      particular the bile acids. Semi-microbore HPLC is useful for concentrating small
      quantities of material and, in combination with an on-line diode array detector,
      for distinguishing between drug related and endogenous components. A novel
      angiotensin II receptor antagonist, GR117289, had proved difficult to analyse by
      thermospray mass spectrometry because of its thermal lability. The use of the
      less thermally dependent technique of ionspray mass spectrometry allowed the
      characterization of nanogram quantities of glucuronic acid metabolites of
      GR117289 in bile.

PMID- 8155904
TI  - Pathology of the salivary glands: the contribution of electron microscopy.
AB  - Electron microscopy has a limited role in the diagnosis of primary salivary gland
      tumors, although it can be helpful in metastatic lesions of possible salivary
      gland origin. The diversity of subtypes in salivary gland tumors, as well as the
      range of histomorphology within any one subtype, is unparalleled in any other
      human tumor. This and their relative infrequency causes diagnostic problems for
      pathologists. Ultrastructural techniques have been of major importance in
      determining the inter-relationship of these tumors for classification purposes,
      revealing the subtle variations in common cellular differentiation pathways,
      determining the organization of tumor cells, and displaying the importance of
      extracellular matrix materials in establishing diagnostic criteria for each of
      the many subtypes. Electron microscopy has also been valuable in non-neoplastic
      salivary gland disease and has an increasing role in experimental studies
      involving tissue from human and animal salivary parenchyma.

PMID- 8155903
TI  - Myoepithelium of salivary glands.
AB  - In salivary glands and other exocrine organs, there are starfish-shaped cells
      that lie between the basal lamina and the acinar and ductal cells. These have
      structural features of both epithelium and smooth muscle cells, and so are called
      myoepithelial cells. Their functions include contraction when the gland is
      stimulated to secrete, compressing or reinforcing the underlying parenchymal
      cells, thus aiding in the expulsion of saliva and preventing damage to the other
      cells. They also may aid in the propagation of secretory and other stimuli. Their
      common developmental origin with the basal cells of the larger ducts is displayed
      in the mature glands by shared structural and immunohistochemical features, but
      most such basal cells do not have the distinguishing features of myoepithelial
      cells, such as myofibrils. Although myoepithelial cells can be identified by
      light microscopy through enzyme histochemistry and special stains and
      immunohistochemistry for their myofibrils, these techniques can be misleading in
      salivary gland neoplasms. Thus, the most reliable means of identifying neoplastic
      myoepithelial cells is with a combination of histochemistry and electron
      microscopy. The extent to which these cells are derived from undifferentiated
      stem cells in both normal and neoplastic growth is controversial. The
      presentation here of transmission electron microscopy (TEM) of well
      differentiated myoepithelial cells in mitotic division indicates that stem cells
      are not necessarily the only source of myoepithelial cells in the later stages of
      salivary gland development or in neoplasia.

PMID- 8155905
TI  - Morphological effects of diabetes on the granular ducts and acini of the rat
      submandibular gland.
AB  - Effects of experimental diabetes on rat submandibular glands have been
      documented, but earlier reports suggested that diabetes caused an extensive
      cellular degeneration and a replacement of the parenchymal cells by fibrous
      connective tissue. Such observations, however, are difficult to reconcile with
      the relatively normal physiological responsiveness of the gland (Anderson and
      Suleiman, 1989). This study, therefore, reexamined the histological,
      histochemical and ultrastructural effects of streptozotocin-induced diabetes on
      rat submandibular glands. The tissues were examined at 3 weeks, and 3 and 6
      months after the induction of diabetes, and compared with glands from age-matched
      controls by both light and electron microscopy. Light microscopically, the
      proportional volumes of the acini and granular ducts remained constant in control
      rats at about 48% and 38% respectively. In diabetic animals the volume density of
      the acini increased progressively to 62%, whereas that of the granular ducts
      decreased to 20%. The diameter and number of granular ducts were reduced in
      diabetic animals, but acinar cell profile area was only affected 6 months after
      the induction of diabetes. Ultrastructurally, there was an accumulation of lipid
      in the acinar cells and, with increasing duration of diabetes, the number of
      autophagic structures in both the acini and the granular ducts increased.
      Although there was evidence of some cellular degeneration it was never excessive.
      Morphometry showed that the volume density of secretory granules within the
      acinar cells was unaffected, but there was a significant reduction in the volume
      density of secretory granules within the granular ducts. Thus, in the rat
      submandibular gland the greatest effect of streptozotocin-induced diabetes was to
      cause hypotrophic changes in the cells of the granular ducts. The relative
      contributions of a direct effect of insulin insufficiency and the hypogonadal
      effects of diabetes, however, are not known.

PMID- 8155909
TI  - Predator-prey dynamics in models of prey dispersal in two-patch environments.
AB  - Models are presented for a single species that disperses between two patches of a
      heterogeneous environment with barriers between patches and a predator for which
      the dispersal between patches does not involve a barrier. Conditions are
      established for the existence, uniform persistence, and local and global
      stability of positive steady states. In particular, an example that demonstrates
      both the stabilizing and destabilizing effects of dispersion is presented. This
      example indicates that a stable migrating predator-prey system can be made
      unstable by changing the amount of migration in both directions.

PMID- 8155908
TI  - A G protein-based model of adaptation in Dictyostelium discoideum.
AB  - A new model is proposed based on signal transduction via G proteins for
      adaptation of the signal relay process in the cellular slime mold Dictyostelium
      discoideum. The kinetic constants involved in the model are estimated from
      Dictyostelium discoideum and other systems. A qualitative analysis of the model
      shows how adaptation arises, and numerical computations show that the model
      agrees with observations in both perfusion and suspension experiments. Several
      experiments that can serve to test the model are suggested.

PMID- 8155906
TI  - A review of electron probe X-ray microanalysis studies of salivary gland cells.
AB  - Electron probe X-ray microanalysis (EPXMA) has now been successfully applied to
      several salivary gland preparations. This paper briefly reviews the principles
      underlying this technique and the specific sample preparation procedures which
      permit accurate measurement of elemental concentrations in the various
      intracellular spaces. Findings from salivary gland studies indicate that
      cytoplasmic and nuclear spaces of nonstimulated acinar cells have high
      concentrations of K and P, and low concentrations of Mg, Ca, and S; and that
      mature secretory granules have high concentrations of Ca and S, and relatively
      low concentrations of K and P. No consistent differences have been found between
      the elemental concentrations of mucous and serous secretory granules. In vivo and
      in vitro EPXMA studies of the elemental changes associated with secretory granule
      maturation indicate there are at least two stages in this process: an early stage
      during which granule S concentration increases in parallel with mass density as
      condensing vacuoles mature into secretory granules, and a late stage during which
      granule mass density and protein content increase with no further elemental
      concentration changes. Findings from other in vivo and in vitro studies indicate
      that secretory granule membranes are permeable to Na, K, and Cl ions because the
      granular concentrations of these elements are altered by electrochemical
      gradients. Recent EPXMA results indicate that cells stimulated with
      parasympathomimetic agonists have decreased K and Cl concentrations, and
      increased Na concentrations. Furthermore, the magnitude of these changes are
      quantitatively consistent with changes measured using radio-isotope equilibration
      and other techniques. In contrast, cells stimulated with the beta-adrenergic
      agonist, isoproterenol, have increased concentrations of Na and Cl, but unchanged
      K concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155907
TI  - The core group revisited: the effect of partner mixing and migration on the
      spread of gonorrhea, Chlamydia, and HIV.
AB  - A set of differential equations are used to model the spread of sexually
      transmitted diseases (STDs) in a one-sex population that includes a core group of
      highly sexually active subjects. The effects of partner mixing between groups and
      migration to and from the core on the equilibrium number of infected are shown
      for gonorrhea, chlamydia, and HIV. The STDs are described by the transmission
      probability per sexual contact and the duration of infectiousness. Partner change
      and intercourse frequencies are estimated from sexual survey data on heterosexual
      behavior. The core group is small (3% of the total population) with a partner
      change frequency 15 times and an intercourse frequency 2 times that of the
      remaining population. The degree of partner mixing and migration between the two
      groups can be varied. The number of sexual contacts in the three types of
      partnerships (core-core, "mixed," remaining population-remaining population) is
      also modeled. The mixed partnerships are assumed to be casual and to have a low
      frequency of intercourse. The model is fairly simple, and the emphasis is on
      qualitative rather that predictive results. The effects of partner mixing are
      found to be strikingly different for gonorrhea, chlamydia, and HIV. With
      increasing partner mixing between groups, gonorrhea shows a small increase and
      then a decrease in the total number of infected, whereas chlamydial infection
      shows a strong increase. For HIV infection the effect depends on the transmission
      probability; when it is 0.001 per sexual contact, the number of infected with HIV
      is almost unaffected by the partner mixing, and when the transmission probability
      is 0.002 per sexual contact, there is a strong increase in the number of HIV
      infected with increasing partner mixing. The effects of migration are also
      different for each disease. With increasing migration between groups, gonorrhea
      is almost unaffected in the total number of infected, whereas chlamydial
      infection shows a strong increase. For HIV the effect again depends on the
      transmission probability; when it is 0.001 per sexual contact, the number of
      infected with HIV shows a strong decrease, and when the transmission probability
      is 0.002 per sexual contact the number of HIV infected reaches its maximum for
      medium strong migration. A sensitivity analysis shows that for all three diseases
      the basic reproductive ratios (R0) and the total number of infected are sensitive
      to duration of infectiousness. In addition, for gonorrhea and chlamydia, RO is
      sensitive to the partner change rates in the core, whereas for HIV, RO is
      sensitive to the frequency of intercourse in the core.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8155912
TI  - The Enneagram: perspective on ourselves, each other and our clients.

PMID- 8155911
TI  - AHNA certificate program in holistic nursing courses: AHNA certificate program in
      healing touch courses.

PMID- 8155910
TI  - Maximum sustainable yield with continuous age structure and density-dependent
      recruitment.
AB  - The problem addressed is that of finding the harvesting policy that will maximize
      the yield and maintain a given population in a steady state. It is assumed that
      the equations describing the evolution of the population and the yield are linear
      but that the equation describing reproduction is nonlinear (density dependence).
      The optimal strategy consists in harvesting two age classes only: a younger age
      class is partially harvested, and an older age class is completely harvested as
      in the linear case. This problem is a particular case of a general abstract
      maximization problem in which, for example, nonlinear mortality or nonlinear
      value of the individuals can also be introduced. The appropriate compactness for
      this problem is obtained from the fact that maximizing sequences are decreasing.

PMID- 8155913
TI  - Environmental equity. The impact of environmental issues on people of color.
      Interview by Mary Szczepanski.

PMID- 8155914
TI  - Additional water is not needed for healthy breast-fed babies in a hot climate.
AB  - In Lahore, Pakistan, a community-based study was conducted to investigate whether
      or not it was necessary to give water to breast-fed infants. From May to November
      1986, 2-4-month-old, breast-fed infants (n = 26) were selected. During the study
      period the maximum temperature ranged between 27.4 and 40.7 degrees C and
      humidity varied between 24 and 77%. Each infant was followed up for 15 days.
      Water was not allowed from day 1 to day 8 and water was allowed ad libitum from
      day 8 to day 15. All infants were subjected to a DDAVP test to estimate the renal
      concentrating capacity on day 15. A significant gain in weight (p < 0.001) was
      observed between day 1 to 8 and 8 to 15. The differences in the values of
      haematocrit and serum sodium between day 8 and 1 and between day 15 and 8 were
      not significant. This indicates that the infants were not dehydrated when water
      was withheld. Furthermore, no significant difference was observed for urine
      specific gravity between day 8 and 1, but urine specific gravity increased
      significantly after the administration of DDAVP (p < 0.001), indicating that, if
      needed, the infants could concentrate urine when water was restricted. It was
      concluded that 2-4-month-old, breast-fed, healthy infants showed no signs of
      dehydration if additional water was not given during the summer season.

PMID- 8155915
TI  - The concentration of bovine IgG in human breast milk measured using different
      methods.
AB  - The bovine IgG concentration in human breast milk was measured using three
      different methods: competition radioimmunoassay (RIA), competition enzyme-linked
      immunosorbent assay (ELISA) and sandwich ELISA. In 36 samples of human breast
      milk taken from mothers on diets including cow's milk, the concentration of
      bovine IgG was significantly higher when measured by either competition RIA or
      ELISA (mean 324.9 +/- 97.4 ng/ml and 396.7 +/- 58.7 ng/ml, respectively) than by
      sandwich ELISA (3.44 +/- 0.48 ng/ml). In 7 samples of human breast milk taken
      from mothers on cow's-milk-free diets of more than one month, the concentration
      of bovine IgG was still within a detectable range (112.3 +/- 41.4 ng/ml) using
      competition ELISA, whereas it was not detected when using sandwich ELISA,
      suggesting that competition ELISA might measure some unknown substances in
      addition to bovine IgG. Gel filtration of pooled human breast milk revealed three
      large fractions. The concentration of bovine IgG in every fraction was
      significantly higher using competition compared with sandwich ELISA, suggesting
      that the difference between these assays does not result from measuring different
      quantities of bovine IgG, or of fragments of this protein. The time course of the
      bovine IgG level was different between each human breast milk sample after taking
      cow's milk. We showed that human breast milk contains bovine IgG at a
      concentration of approximately 3 ng/ml when analysed using sandwich ELISA. This
      level is comparable to the quantity of either casein or of beta-lactoglobulin in
      human breast milk. Bovine IgG might be an important allergen in cow's milk
      allergy due to the quantity in human breast milk.

PMID- 8155916
TI  - Type of milk feeding in infants and young children up to 19 months of age in
      three socio-economic groups in Madrid.
AB  - The feeding practices of 344 children in Madrid between 3 and 19 months were
      investigated by controlled interview or their mothers of care-takers. Four
      different types of milk were given to the children: human milk, infant formula,
      follow-on formula and cow's milk. Three periods could be defined when infants
      were most likely to change from one milk type to another. The majority of babies
      changed from human milk to infant formula some time in the first three months of
      life. At between four and six months, about half the sample changed to a follow
      on formula and, finally, around the baby's first year formula was substituted for
      cow's milk. Differences in feeding behaviour could be observed among socio
      economic groups, but were not statistically significant. Feeding patterns closely
      followed international recommendations for infant feeding.

PMID- 8155917
TI  - Urinary excretion of epidermal growth factor and transforming growth factor-alpha
      in breast-fed and formula-fed infants.
AB  - Urinary epidermal growth factor (EGF) and transforming growth factor-alpha (TGF
      alpha) concentrations were determined by radioimmunoassay in a longitudinal study
      analyzing 348 24-h urine specimens of 32 infants (16 breast-fed, 16 formula-fed)
      during the first 16 weeks of life. EGF excretion showed a statistically
      significant increase from 6.0 +/- 2.5 to 14.1 +/- 4.9 micrograms/g creatinine
      (mean +/- 1 SD) during the investigation period. TGF-alpha levels were fairly
      constant throughout this period. Comparing breast-fed infants, with more than 100
      fold higher ingestion of EGF and TGF-alpha, with formula-fed infants, no
      significant differences in urinary EGF and TGF-alpha excretion were observed.
      These results do not rule out a systemic effect of EGF and TGF-alpha after
      intestinal absorption in breast-fed infants. The results suggest, however, that
      urinary EGF and TGF-alpha originate mainly from sources other than intestinal
      absorption.

PMID- 8155918
TI  - Continuous positive airway pressure.

PMID- 8155919
TI  - Short-term effects of blood transfusion on blood volume and resting peripheral
      blood flow in preterm infants.
AB  - The effects of blood transfusion on cardiac output and blood pressure are
      variable, but resting peripheral blood flow (RPBF) may be a sensitive indicator
      of changes in blood volume. The purpose of this investigation was to study the
      effects of red cell transfusion on blood volume (Evans blue), blood pressure,
      RPBF in the leg (strain-gauge plethysmography) and blood viscosity (cone-plate
      viscometer) in preterm infants during the first week after birth. Fourteen
      infants with mean +/- SD birth weight of 1658 +/- 429 g, gestational age 33 +/- 3
      weeks and postnatal age 64 +/- 40 h received 18 +/- 4 ml/kg of packed red cells
      (red cells 11 +/- 2 ml/kg, plasma 7 +/- 1 ml/kg) because their hematocrit was
      less than 0.45 l/1. Mean blood volume before transfusion was 88 +/- 15 ml/kg. The
      increase in blood volume (9 +/- 4 ml/kg) measured 4 to 6 h after transfusion was
      smaller than the transfused volume (18 +/- 4 ml/kg), due to a shift of plasma to
      the extravascular space. The plasma shift increased with increasing
      pretransfusion blood volume (r = 0.70; p = 0.007). Red cell transfusion caused an
      increase in RPBF by 25% (p < 0.01), whereas systolic blood pressure (BP)
      increased by only 12%. Peripheral resistance (R = BP/RPBF) decreased by 9% (p <
      0.01). Blood viscosity (eta) increased by 21% (p < 0.001) and vascular hindrance
      (R/eta) decreased by 24% (p < 0.001), indicating vasodilatation of limb arteries.
      The increase in RPBF and the decrease in hindrance were particularly pronounced
      in infants with high pretransfusion blood volume.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8155920
TI  - Maternally acquired immunity in newborns from women infected by the human
      immunodeficiency virus.
AB  - Maternally acquired immunity was studied in 16 pairs of human immunodeficiency
      virus (HIV)-seropositive women and their newborns, and was compared to 18 control
      mother-newborn pairs. The HIV-infected women had higher IgG levels than the
      control subjects, but no difference was observed between newborn samples,
      presumably due to the limited placental IgG transfer in the HIV group. A poor
      type 2 poliovirus antibody transfer was also noted in this group. The population
      of newborns lacking demonstrable measles antibodies was higher in the HIV group
      than in the control group, probably because many of the HIV-infected mothers
      lacked measles antibodies also. These results show that maternally acquired
      immunity may be affected to newborns from HIV-infected women, either because of
      low maternal serum antibody levels or deficient transplacental transfer. If so,
      the measles vaccine schedule should be revised for these children and the same
      should be done for future passive immunization regarding fetus protection in
      pregnant HIV-seropositive women.

PMID- 8155922
TI  - Eye protection during phototherapy.

PMID- 8155921
TI  - SIDS outdoors and seasonality in Sweden 1975-1987.
AB  - In order to link the reported increasing incidence of SIDS in Sweden to
      environmental or other risk factors, we compared birth records and circumstances
      of deaths in infants who died in 1975-1977 with those who died a decade later,
      1985-1987. The number of liver births differed by only 6850 in these two periods.
      Data were acquired from autopsy records of the decreased infants and matched with
      their respective birth certificates which were obtained from the National Board
      of Health and Welfare. The reported postperinatal incidence of SIDS increased
      from 0.51 per 1000 in 1975-1977 to 0.93 per 1000 in 1985-1987. No significant
      differences in boy/girl ratio, birth weight, gestational age or age at death were
      found in the two periods. While the number of infants who died at night indoors
      in their own bed remained almost unchanged, the number of infants who died
      outdoors in baby carriages during the cold season increased almost four-fold. The
      observed increase in incidence could, to a large extent, be related to the
      increase in outdoor deaths. We speculate that increased incidence of smoking
      among young women as well as other changes in lifestyle may have been
      contributing factors.

PMID- 8155923
TI  - Adverse reactions in healthy and immunocompromised children under six years of
      age vaccinated with the Danish BCG vaccine, strain Copenhagen 1331: implications
      for the vaccination policy in Sweden.
AB  - A retrospective analysis of the adverse reactions reported between 1979 and 1991,
      in the 139,000 children under six years of age vaccinated in Sweden with the
      Danish BCG vaccine, strain Copenhagen 1331, showed an incidence of 1.9 per 1000
      vaccinated children. Regional lymphoglandular swellings and/or abscesses were
      most commonly reported in 1.4 per 1000. Serious, disseminated, BCG infections
      developed in four infants vaccinated neonatally. Three of the infants suffered
      from severe, combined, immunodeficiency syndrome, undiagnosed at the time of
      vaccination. The incidence of severe, combined, immunodeficiency syndrome was
      higher in the BCG-vaccinated population (4 per 100,000 infants vaccinated within
      a year of their births), compared with all newborns in Sweden (1 per 100,000).
      The mean age at the onset of symptoms was 2.4 months for the seven non-BCG
      vaccinated infants versus 1.3 months for the four BCG-vaccinated ones, while the
      immunodeficiency syndrome was diagnosed at an average age of 7.6 months in those
      who were not vaccinated versus 5.3 months in those BCG-vaccinated. It is
      recommended that the selective BCG vaccination of infants at high risk of
      exposure to tuberculosis should be postponed to six months of age to reduce the
      risk of inoculating infants suffering from immunodeficiency syndromes.

PMID- 8155925
TI  - Is the incidence of childhood coeliac disease in Sweden still rising?

PMID- 8155924
TI  - Prognostic factors in meningococcal disease and a new scoring system.
AB  - One-hundred-and-forty patients diagnosed as having meningococcal disease have
      been investigated retrospectively with respect to prognostic factors. The overall
      mortality was 8.6%, the mortality rate of the infants under 6 months of age being
      higher than that of the other groups. In cases where there was no meningitis or
      leucocytosis, the presence of hypotension, disturbed consciousness and diffuse
      petechiae increased the mortality rate significantly. High fever did not have any
      effect on mortality. We propose a new practical and reliable scoring system for
      meningococcal disease for determining the influence of prognostic factors on
      mortality.

PMID- 8155926
TI  - Sodium-lithium countertransport and family history of hypertension in childhood.
AB  - We have studied the relationship between sodium-lithium countertransport,
      determined in childhood, and family history of hypertension. Countertransport was
      measured in healthy children and those with secondary hypertension. There was no
      significant difference in countertransport between these two groups. In the
      normal children (n = 52, median age 6.8 years), there was a positive relationship
      between body mass index and countertransport (rs = 0.34, p < 0.02). A positive
      relationship between family history of hypertension using a ranked scoring
      system, and countertransport, not related to age, body mass or blood pressure (n
      = 34, rs = 0.63, p < 0.001) was also found. There was no significant relationship
      between intracellular sodium concentration and countertransport. These data
      confirm that countertransport in normal children is related to body mass index
      and indicate that a genetic predisposition to primary hypertension marked by
      sodium-lithium countertransport is identifiable in childhood.

PMID- 8155927
TI  - Typical technetium dimercaptosuccinic acid distribution patterns in acute
      pyelonephritis.
AB  - Technetium dimercaptosuccinic acid renal scintiscans in 37 children with clinical
      diagnosis of acute pyelonephritis were reviewed. In 18 children, follow-up
      scintigraphy was obtained after an interval ranging from 5 to 8 months. Uptake
      abnormalities were found in 89% of the children (74% of the kidneys). We were
      able to identify four typical pathological uptake patterns: (i) pole defect(s),
      usually wedge shaped (60%); (ii) lateral wedge shaped defect (4%); (ii) scattered
      multiple defects (21%); and (iv) swollen kidney without areas of diminished
      uptake (15%). Remaining pathology at follow-up was found in 52% of the kidneys.
      Vesicoureteric reflux was present in 33% of the children with scintigraphic signs
      of pyelonephritis. Frequencies of parenchymal changes in the acute phase and at
      follow-up were not significantly correlated to the presence of reflux.

PMID- 8155928
TI  - Type B hepatitis and primary hepatocellular carcinoma in a nine-year-old French
      boy.

PMID- 8155929
TI  - Systemic activity of inhaled topical steroid in toddlers studied by knemometry.
AB  - The short-term linear growth rate of the lower leg in toddlers was measured and
      evaluated in order to study the possible effect of inhaled budesonide on this
      factor in toddlers with mild recurrent wheezing. The short-term linear growth
      rate of the lower leg was measured weekly using a hand-held knemometer. Eighteen
      toddlers aged 13-36 months (mean 27 months) with a history of recurrent wheezing
      requiring inhaled topical steroids, but without need of regular medication during
      the months prior to the study, were studied. The children were randomized blindly
      through three consecutive treatment periods of four weeks with placebo or
      budesonide in daily doses of 200 micrograms and 800 micrograms administered as a
      pressurized aerosol inhaled via a spacer with a face mask. Twenty-nine percent
      (median) of the nominal dose was delivered at the mouth of the children. Three
      children were withdrawn because of exacerbations and one because of non
      compliance. The precision of the measurement procedure was 51 microns/day. The
      mean growth rate during placebo, low-dose and high-dose steroid treatment was 92
      microns/day, 114 microns/day and 46 microns/day respectively. The growth rate
      during the high-dose treatment was suppressed significantly compared to placebo
      treatment (95% CI -76 microns/day to -17 microns/day), whereas the growth rate
      during low-dose steroid treatment was indistinguishable from placebo treatment
      (95% CI -7 to +52 microns/day). In conclusion, measurement of short-term linear
      growth rate by knemometry in toddlers is a fast and gentle method with a high
      level of precision.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8155931
TI  - Infantile rotavirus diarrhoea and development of allergy.

PMID- 8155933
TI  - A new case of severe congenital nemaline myopathy.
AB  - The case of a neonate with a rapidly fatal course of nemaline myopathy is
      reported. Neonatal history and clinical findings suggested a postasphyxia
      syndrome, but dependence on mechanical ventilation in the absence of severe brain
      damage or evidence of heart and lung involvement prompted us to perform a muscle
      biopsy. The typical rod-shaped bodies of nemaline myopathy were observed in
      skeletal and heart muscle which is unusual in infantile forms. Neonatal bone
      fractures, which have not been reported previously, were detected. Due to the
      rapid evolution of the neonatal form, many of these patients may die undiagnosed
      in the perinatal period, the families remaining unaware of the existence of the
      genetic disorder. Therefore, if severe hypotonia persists in a neonate, together
      with dependence on assisted breathing, specific examinations, such as muscle
      enzyme determination, NCV, EMG and if indicated, muscle biopsy should be
      performed to rule out neuromuscular disease.

PMID- 8155930
TI  - Intra-articular glucocorticoids in early juvenile chronic arthritis.
AB  - The efficacy of intra-articular glucocorticoid injections in the early phase of
      knee joint synovitis was studied in 79 children with juvenile chronic arthritis
      (42 girls and 37 boys). Half of the injections were given within the first six
      months from the onset of the disease. The probability of a patient staying in
      remission was much higher in triamcinolone-treated patients than in patients
      receiving methylprednisolone (p < 0.0005, Breslow statistics). Using multivariate
      analysis there was a significant association between the length of remission and
      the synovial fluid polymorphonuclear leucocyte proportion (SF-PMN%). Patients
      with a high SF-PMN% tended to have shorter remissions than those with a low SF
      PMN% (improvement of the fit in stepwise model: chi-square = 8.81, p < 0.005).
      The difference between triamcinolone and methylprednisolone groups was still
      clearly evident two years after injection.

PMID- 8155932
TI  - Fatal neonatal lactic acidosis with respiratory insufficiency due to complex I
      and IV deficiency.
AB  - We present a newborn boy who died after 53 days of life in respiratory failure
      with lactic acidosis. Analysis of skeletal muscle mitochondria demonstrated a
      combined defect in complexes I and IV of the respiratory chain. The boy had
      severe muscle hypotonia but no signs of encephalopathy, illustrating the
      variation in multi-organ presentation of mitochondrial defects.

PMID- 8155934
TI  - Neuroblastoma IV-S in a patient with bilateral microphthalmia.
AB  - Neuroblastoma, a tumor of post-ganglionic sympathetic neurons, may be associated
      with a variety of genetic defects and congenital malformations (1). We report a
      case of neuroblastoma (NB) stage IV-S (2) in an infant with bilateral
      microphthalmia and other ocular malformations.

PMID- 8155935
TI  - Antigen-reduced infant formulae. ESPGAN Committee on Nutrition.

PMID- 8155937
TI  - [Preliminary study of cytochemistry on thin-white coating of tongue with
      deficiency-cold syndrome].
AB  - The method of qualitative and quantitative analysis and localization of
      cytochemistry were used to observe the epithelial cells of the thin-white coating
      of tongue from 25 patients with Deficiency Cold Syndrome (DCS) and 20 normal
      persons. Results showed that the level of intracellular DNA, PAS of the
      epithelial cells in the DCS group were markedly enhanced, while the activities of
      succinate dehydrogenase (SDH) and acid alpha-naphthyl acetate esterase (ANAE)
      were reduced significantly compared to normal group, P < 0.05, 0.001, 0.001, 0.01
      respectively.

PMID- 8155939
TI  - [Qing-shen tiao-zhi tablet in the treatment of hyperlipemia in the middle and old
      aged].
AB  - The effect of Qing-Shen Tiao-Zhi (QSTZ) tablet which consisted of Rheum palmatum
      and Alismatis orientale etc. on serum TC, TG, HDL-C, LDL-C and atherogenic index
      (AI) was reported in 73 senile hyperlipemic patient, while another 21 patients
      took Yue Jian Cao (YJC) oil capsule. The results showed that total effective rate
      was 91.7% in QSTZ group, and 71.43% in the YJC group (P < 0.05). The levels of
      TC, TG and LDL-C before and after medication showed significant difference, P <
      0.01 in QSTZ group and that there was only a few persons those P < 0.05 in
      control group. About AI, it revealed in QSTZ and control group as P < 0.01 and >
      0.05 respectively.

PMID- 8155938
TI  - [Changes in oxygen free radical and prostacyclin in thromboangiitis obliterans
      and its relationship with syndrome differentiation].
AB  - Malondialdehyde (MDA) and 6-keto-PGF1 alpha levels in plasma and erythrocyte
      superoxide dismutase activities (Ery-SODA) were observed in 56 cases of
      thromboangiitis obliterans (TAO). The results showed that: (1) Ery-SODA and 6
      keto-PGF1 alpha levels lowered and MDA raised significantly in TAO (P < 0.01),
      compared with that in control. (2) 6-keto-PGF1 alpha levels were markedly related
      with Ery-SODA and MDA in TAO (P < 0.01). (3) Ery-SODA and 6-keto-PGF1 alpha
      levels were lower and MDA higher in III phase of TAO than that in II phase. (4)
      Ery-SODA and 6-keto-PGF1 alpha levels markedly declined and MDA contents elevated
      significantly in Dampness-Heat (DH) and Heat-Toxin (HT) group, compared with that
      in Yin-Cold (YC) group and Blood-Stasis (BS) group, respectively (P < 0.05, P <
      0.01); all above substances between YC and BS group or between DH and HT group
      had no significant differences (P > 0.05). (5) Ery-SODA and 6-keto-PGF1 alpha
      levels were lower and MDA higher in Heat Syndrome than that in Cold Syndrome (P <
      0.01). It suggested that oxygen free radical and lipid peroxide response that
      might participate in vascular endothelial cell injury in TAO markedly increased
      and the detection of these substances might provide complementary evidences for
      syndrome differentiation of TAO.

PMID- 8155936
TI  - Intake and growth of breast-fed and formula-fed infants in relation to the timing
      of introduction of complementary foods: the DARLING study. Davis Area Research on
      Lactation, Infant Nutrition and Growth.
AB  - We examined if the timing of introduction of solid foods was related to growth,
      intake, morbidity, activity or motor development among infants either breast fed
      or formula fed until > or = 12 months of age. Breast-fed infants given solids
      before 6 months of age (earlysol) consumed less breast milk at 6 and 9 months of
      age than those given solids > or = 6 months (latesol); thus total energy intake
      did not differ between groups. Z scores for weight, length and weight-for-length
      at 1-18 months did not differ between groups. Latesol infants gained less weight
      from 6 to 9 months but not during any other interval. Neither activity level nor
      morbidity differed between groups, but several developmental milestones occurred
      earlier in the earlysol versus the latesol group, probably due to reverse
      causation. Among formula-fed infants, timing of introduction of solid foods was
      not related to intake, growth, activity or morbidity. We conclude that solid
      foods given before 6 months of age generally replace the milk source among breast
      fed but not formula-fed infants.

PMID- 8155940
TI  - [Jiangzhi koufu ye in the treatment of essential hyperlipemia].
AB  - The effect of Jiangzhi Koufu Ye (JZKFY) for serum lipid was verified. 333
      patients were treated with JZKFY as treated group, while those with vitamin E as
      control. It was found that JZKFY was able to lower TC, TG, TC-HDL-ch/HDL-ch and
      raise HDL-ch very significantly (P < 0.001) after 14 weeks and the effect were
      maintained at least 4 weeks. The marked effective and the total effective rate
      were 59% and 92% respectively. Except for HDL-ch, all other indexes were better
      than the control. No obvious side effects were found.

PMID- 8155941
TI  - [Comparison of lipoperoxidative damage in plasma and platelet with the ratio of
      thromboxane A2 and prostaglandin I2 in blood stasis syndrome with coronary heart
      disease].
AB  - In order to study the biochemical and pathophysiological mechanism of the Blood
      Stasis Syndrome (BSS) or Non-BSS of coronary heart disease (CHD) patients, the
      activities of SOD, Selenium-glutathione peroxidase, the content of LPO in plasma
      and platelets and the contents of TXB2 and 6-keto-PGF1 alpha in plasma were
      determined in 109 BSS and Non-BSS of CHD patients compared with 98 healthy
      controls. It was discovered that the contents of TXB2, LPO, PL-LPO, and the ratio
      of TXB2/6-keto-PGF1 alpha were significantly increased in BSS-CHD patients
      compared with controls and Non-BSS-CHD patients. It was also discovered that the
      SOD activities and the contents of 6-keto-PGF1 alpha decreased significantly in
      Non-BSS-CHD patients. The results suggested that the injury of platelets by
      oxygen free radicals might be one of the primary injury factors in BSS-CHD
      patients. Our conclusion is that PGI2, SOD belong to the category of Heart-Qi,
      while TXA2, LPO to the Blood category. Therefore TXB2, 6-keto-PGF1 alpha, SOD,
      LPO should serve as some of the objective indexes for BSS patients of CHD.

PMID- 8155944
TI  - [Mechanism of guizhi tang on dual-directional thermoregulation--effect of
      prostaglandin E2 level in hypothalamus of rats].
AB  - Antipyretic action was found in febrile rats induced by yeast, and body
      temperature was elevated in hypothermia rats induced by aminopyrine, when 10 g/kg
      of Guizhi Tang (GZT) was administered per os. The content of prostaglandin E in
      the hypothalamus of rats was determined with the radioimmunoassay. Administration
      of GZT in 10 g/kg p.o. could both decrease the PGE2 level of hypothalamic blood
      in febrile rats, and increase the PGE2 level in hypothermia rats. Antipyretic
      action of GZT was also displayed when microinjection of PGE2 into the lateral
      ventricle which produced fever in rats. The evidence was provided that GZT might
      carry out at least part of the dual-directional regulating action in body
      temperature through the promotion or inhibition on PGE2 synthesis, release, or
      metabolism in the thermoregulatory center.

PMID- 8155942
TI  - [Effect of electro-acupuncture at neiguan P6 on sino-atrial conduction in
      patients without sick sinus syndrome].
AB  - The effects of electro-acupuncture (EA) at Neiguan P6 served as a main point and
      Jianshi P5 as an adjunct point on sino-atrial conduction were studied in 10
      patients with normal sinus nodal function. The results were as follows: During EA
      and in period of intrinsic heart rate (IHR0) the sinoatrial conduction times
      (SACT) from sinus node electrogram were significantly shortened than that in
      control, (P < 0.01 and P < 0.001, respectively). But the SACT could not be
      further shortened by stimulating the acupoints during IHR0 (P < 0.05). It is
      suggested that EA at Neiguan P6 as a main point could improve sino-atrial
      conductivity in most patients with normal sinus node function, which seems to be
      mediated by autonomic nerve system. The normal value of SACT after autonomic
      nerve blockade needs to be established.

PMID- 8155943
TI  - [Effect of Salvia miltiorrhizae in the treatment of 36 infantile acute toxic
      myocarditis].
AB  - Control observation of infantile acute toxic myocarditis treated by Salvia
      miltiorrhizae (SM) showed that 36 cases were clinically cured through SM
      treatment. The total effects have obvious advantages over Western Medicine
      control group, P < 0.01. The period of hospitalization and ECG normalization, of
      control group was significantly longer than that of SM treated group, P < 0.001
      respectively.

PMID- 8155946
TI  - [Effect of Rhodobryum roseum on hemorheology following acute coronary occlusion
      in dogs].
AB  - Following acute occlusion of the left anterior descending coronary artery, the
      significant and constant hemorheologic changes were observed in venous blood from
      ischemic area. 30 min after occlusion, the high shear rate (r = 230s-1), middle
      shear rate (r = 23s-1) and low shear rate (r = 5.75s-1), viscosity of whole blood
      (eta b) increased significantly, and this change occurred in viscosity of plasma
      (eta p) and in red cell electrophoretic time (RCET) also. These increases
      continued thereafter. In another group of dogs, 30 min after coronary occlusion,
      rapid dripping was performed with Rhodobryum roseum (Huixincao) injection from
      right femoral vein. After 10 min, eta b at all shear rate reduced significantly,
      and this reduction was observed in eta p and in RCET also. These findings
      suggested that the hyperviscosity syndrome developed in acute myocardial ischemic
      could be blocked by Hui Xin Cao.

PMID- 8155945
TI  - [Transportation trends after rat renal intracapsular injection of Salvia
      miltiorrhizae].
AB  - The concentration of Salvia miltiorrhizae (SM) was detected at different time
      after renal intracapsular injection in S.D rats. It showed that SM concentration
      was higher in kidney than in plasma (P < 0.05). SM concentration in kidney
      increased gradually, it reached the peak at 24 hour and still remained in higher
      level at 48 hour. The SM injected in renal capsule could be passively transported
      to renal tissue and maintained at a high level. This result demonstrated that
      renal intracapsular injection could be applied as an important therapeutical
      method for different renal disease.

PMID- 8155948
TI  - [Progress in treatment of cholelithiasis with non-operative therapy].

PMID- 8155947
TI  - [Effect of improving memory and inhibiting acetylcholinesterase activity by
      invigorating-qi and warming-yang recipe].
AB  - Invigorating-Qi and Warming-Yang (IQWY) had a good curative effect to some senile
      diseases such as senile dementia, senile hypomnesia etc. This experiment was
      designed for probing into the therapeutical mechanism of IQWY recipe. BALB/C pure
      bred mice were divided into five groups. Group I was taken per os of invigorating
      Qi (IQ), Group II warming Yang (WY), Group III IQWY drugs, Group IV was dysmnesia
      model, and Group V blank control group injected with normal saline only. All
      groups except Group V were injected scopolamine (5mg/kg) intraperitoneally to
      induce dysmnesia model after medication. IQ drug consisted of Codonopsis
      pilosula, Astragalus membranaceus, Poria cocos, and Glycyrrhiza uralensis, WY
      drug of Cynomorium songoricum, Epimedium brevicornum and Cuscuta chinensis, while
      IQWY recipe consisted of both IQ and WY drugs. The results showed that IQ, WY and
      IQWY had an evident antagonistic action to Scopolamine induced dysmnesia mice,
      and could improve their memory. The erroneous times of the animal's reaction in
      Group I, II and III were less than those in Group IV, P < 0.05 or P < 0.01.
      Acetylcholinesterase (AchE) activity in the mice could be inhibited by IQ, WY and
      IQWY also. The activity in Group I, II and III was less than that in Group IV and
      V, P < 0.05 or P < 0.01. The therapeutic mechanism of IQWY was in connection with
      its effect to M-cholinergic transmitters of central nervous system.

PMID- 8155949
TI  - [Exploration on essence of yang-ming fu-shi syndrome from viewpoint of
      traditional Chinese medicine combined with Western medicine].

PMID- 8155950
TI  - [Protection of Chinese medicinal herb extracts against cerebral ischemia
      reperfusion injury].

PMID- 8155951
TI  - No beds and long waits in the A&E department.

PMID- 8155952
TI  - Should postmenopausal women be eligible for in vitro fertilization?

PMID- 8155953
TI  - Initial nursing assessment and management of burn-injured children.
AB  - Following a burn injury, children can deteriorate very quickly and prompt
      accurate assessment by the accident and emergency nurse is therefore essential.
      This article outlines the initial assessment and management of paediatric burns.

PMID- 8155954
TI  - Nurse/patient communication within a bilingual health care setting.
AB  - Communication and the interactions that take place between nurse and patient are
      the foundation of nursing care. However, in practice, cross-cultural
      communication is often inadequate and therefore the health care needs of many
      cultural groups are not being met. An examination of language switching within
      nurse/patient interaction in a bilingual setting provides a further dimension for
      the study of cross-cultural communication.

PMID- 8155955
TI  - Sleep, wakefulness and the nurse.
AB  - Sleep habits differ between the city dweller and the countryman, and the child
      and the elderly person. In addition, factors such as summertime, hospitalization
      and abuse of tranquillizers all have repercussions on sleep. This article
      examines the variations in sleep habits in different populations, and the effect
      of environmental factors on sleep.

PMID- 8155956
TI  - Use of games in the clinical setting as an aid to teaching.
AB  - Gaming is increasingly being used in nursing curricula as an alternative form of
      learning in the clinical setting. This article discusses the advantages and
      disadvantages of the use of games and describes the design of a game for use by
      any skill mix of staff.

PMID- 8155957
TI  - Educating a patient with diabetes about foot care.
AB  - Patient education is a central part of diabetic care. Evaluating the
      effectiveness of education can be difficult, especially when patients refuse to
      accept the responsibility that knowledge imparts. Those patients identified as
      being at risk of developing neuropathic foot ulcers and who are unable or
      unwilling to accept responsibility for their care need to be closely supervised
      by the health care team. Patient education should be tailored to encompass
      cultural and religious factors as far as possible.

PMID- 8155958
TI  - Problem solving using soft systems methodology.
AB  - This article outlines a method of problem solving which considers holistic
      solutions to complex problems. Soft systems methodology allows people involved in
      the problem situation to have control over the decision-making process.

PMID- 8155959
TI  - Should we have an unrestricted right to reproduce?

PMID- 8155960
TI  - Nurse-aid management of psychiatric emergencies: 2.
AB  - This article, the second in a series on psychiatric emergencies, will focus on
      the following emergencies and their attendant interventions: mania, acute anxiety
      and acute depression. The common theme of these otherwise diverse syndromes is
      that they are all affective disorders, relating to mood and emotional state.

PMID- 8155961
TI  - Confidentiality, patients and the law.
AB  - Doctors and nurses have a legal duty to respect their patients' confidentiality.
      Failure to do so could lead to removal from the register. This article discusses
      the issue of confidentiality and highlights the exceptions to the rule.

PMID- 8155962
TI  - PREPP: who will meet the costs?

PMID- 8155963
TI  - Government's U-turn over Guy's: common sense or betrayal?

PMID- 8155964
TI  - An outbreak of hospital-acquired cryptosporidiosis.
AB  - Cryptosporidium is a common cause of acute, self-limiting gastroenteritis in
      otherwise healthy subjects. In immuno-compromised patients, however, infection
      with this organism can be life threatening. The possible factors that allowed
      transmission of Cryptosporidium from a patient with acquired immune deficiency
      syndrome to nursing staff are examined in this article.

PMID- 8155965
TI  - Pain relief after major gynaecological surgery.
AB  - The effect of Voltarol, administered routinely, in reducing the postoperative
      requirement for opioid drugs was monitored using patient-controlled analgesia.
      Omnopon consumption was recorded together with pain scores. The significance of
      the results is discussed with reference to the dosage and timing of analgesia and
      to nursing practice.

PMID- 8155966
TI  - Interpretations of illness and non-compliance with nursing care.
AB  - This article examines some of the factors that lie behind patient non-compliance
      with care regimens, paying particular attention to patients' constructions of
      their illness. The nature of control in encounters between patients and
      professionals is explored using examples drawn from studies of doctor/patient
      interactions as a basis for understanding the issues.

PMID- 8155967
TI  - Error and trial: the extended role dilemma.
AB  - In spite of recent developments there is still considerable conflict over the
      definitions of extended role and competency. This article reviews the legal and
      professional support systems underpinning the adoption by nurses of duties
      traditionally considered to be doctors' tasks.

PMID- 8155968
TI  - Nursing care of a child with acute glomerulonephritis.

PMID- 8155969
TI  - Nursing can never have a unified theory.

PMID- 8155970
TI  - Moral and ethical dilemmas in relation to research projects.
AB  - Nurses involved in ward-based research projects may face many moral and ethical
      dilemmas. As the number of research studies increases, nurses must be aware of
      their responsibilities to the research team, their patients and their profession.

PMID- 8155971
TI  - Nurse-aid management of hypothermia.
AB  - There are certain groups in our society that are vulnerable to cold weather: the
      elderly, the homeless and young children. This article discusses the causes of
      hypothermia and outlines nurse-aid interventions and prevention strategies.

PMID- 8155972
TI  - Analysis of health rationing policies in the NHS.
AB  - Explicit rationing policies are beginning to appear in the NHS in response to the
      increasing demand for health care and rising treatment costs. Such policies
      challenge the traditional values upon which nursing in the UK is founded. This
      article examines the case for rationing and its implications for nursing.

PMID- 8155973
TI  - A sense phosphorothioate oligonucleotide directed to the initiation codon of
      transcription factor NF-kappa B p65 causes sequence-specific immune stimulation.
AB  - Antisense oligonucleotides have proved effective in achieving targeted inhibition
      of gene expression. In such experiments, sense oligonucleotides have frequently
      been used as a control for nonspecific effects, but the results have been
      variable, raising questions about the reliability of sense oligomers as a
      control. It is possible that some of the effects of sense oligonucleotides may be
      specific. We have shown that phosphorothioate antisense oligonucleotides to the
      p65 subunit of NF-kappa B, a transcription factor, cause a block in cell
      adhesion. In our efforts to test the efficacy of NF-kappa B p65 oligonucleotides
      in vivo, we unexpectedly observed that the control p65-sense, but not the p65
      antisense, oligonucleotides caused massive splenomegaly in mice. In the current
      study we demonstrate a sequence-specific stimulation of splenic cell
      proliferation, both in vivo and in vitro, by treatment with p65-sense
      oligonucleotides. Cells expanded by this treatment are primarily B-220+, sIg+ B
      cells. The secretion of immunoglobulins by the p65-sense oligonucleotide-treated
      splenocytes is also enhanced. In addition, the p65-sense-treated splenocytes, but
      not several other cell lines, showed an upregulation of NF-kappa B-like activity
      in the nuclear extracts, an effect not dependent on new protein or RNA synthesis.
      These results demonstrate that phosphorothioate oligonucleotides can exert
      sequence-specific effects in vivo, irrespective of sense or antisense
      orientation.

PMID- 8155974
TI  - Inhibition of HIV-1 replication in cultured cells with antisense oligonucleotides
      encapsulated in immunoliposomes.
AB  - Antisense oligonucleotides inhibit HIV replication in vitro, but their activity
      is limited by their sensitivity to nucleases and low cellular uptake. To see
      whether these problems could be circumvented, we compared effects of HIV-1 rev
      and tat gene-specific antisense phosphodiester or phosphorothioate
      oligonucleotides, either free in solution or encapsulated in antibody-targeted
      liposomes (immunoliposomes), on acutely or chronically infected cells.
      Phosphodiester antisense oligonucleotides were inactive in their free form in
      acutely and chronically infected cells (up to a concentration of 50 microM). When
      encapsulated in immunoliposomes directed to HLA class I molecules expressed by
      targeted cells, they inhibited viral replication (at a concentration of 0.5
      microM) in acutely infected cells in a sequence-specific manner. The same
      phosphodiester antisense oligonucleotides in liposomes had no antiviral activity
      in chronically infected cells. In acutely infected cells, phosphorothioate
      oligonucleotides free in solution inhibited the replication of HIV without
      sequence specificity and had slightly greater activity, also nonspecific, when
      encapsulated in liposomes. Phosphorothioate antisense (anti-rev) oligonucleotides
      specifically blocked HIV replication in chronically infected cells. When
      encapsulated in targeted liposomes the efficiency of inhibition for these cells
      was increased by at least 60-fold relative to the same oligonucleotide free in
      solution.

PMID- 8155976
TI  - Preparation and physical properties of conjugates of oligodeoxynucleotides with
      poly(delta)ornithine peptides.
AB  - Oligodeoxynucleotides (12-mers) having either a 3' aminolinker or both 3' and 5'
      aminolinker groups were synthesized and then reacted with N
      iodoacetoxysuccinimide. Separately, a series of peptides, consisting of cysteine
      carboxyamide and a varying number of residues of ornithine coupled through their
      side-chain amino groups, was prepared, leaving on the final Fmoc protecting
      group. Reaction of each Fmoc-peptide with an activated oligodeoxynucleotide
      yielded the desired conjugates, which were purified by an Fmoc-on/Fmoc-off two
      step reversed-phase HPLC procedure. On hybridization with a complementary
      unmodified 12-mer oligodeoxynucleotide, it was found that there is a gradual
      increase in melting temperature with the number of ornithine residues, whereas
      the appended peptide did not perturb the B form of the duplex.

PMID- 8155975
TI  - Targeting of antisense DNA: comparison of activity of anti-rabbit beta-globin
      oligodeoxyribonucleoside phosphorothioates with computer predictions of mRNA
      folding.
AB  - To assess the usefulness of computer-assisted modeling of mRNA as an aid in
      design of antisense DNA, the efficiency of inhibition of translation of rabbit
      beta-globin mRNA by various antisense sequences was compared with calculated
      structures of the mRNA. The model obtained by consideration of 30 lowest-energy
      computer-simulated structures is consistent with the high accessibility of the
      AUG initiation codon region known from digestion with nucleases and with previous
      antisense inhibition studies reported in the literature. Additional antisense
      inhibition data were obtained with 20-mer phosphorothioate oligonucleotides,
      targeted to regions of beta-globin mRNA differing moderately in their degree of
      participation in intramolecular folding. The efficiency of translation arrest by
      the oligonucleotides in cell-free expression systems (wheat germ extract and
      rabbit reticulocyte lysate) was obtained by measuring incorporation of
      [35S]methionine into total protein, and corrected for sequence-nonspecific
      inhibition using brome mosaic virus mRNA. In the presence of RNase H (wheat germ
      system), the inhibitory activity of the oligonucleotides showed correlation with
      the calculated secondary structure of mRNA, in particular at low oligonucleotide
      to-mRNA ratios (correlation coefficient, 0.95). No correlation was observed in
      the reticulocyte lysate system, in which the inhibition is mediated by
      translational arrest.

PMID- 8155977
TI  - Specificity of interaction of pyrimidine oligonucleotides with DNA at acidic pH
      in the presence of magnesium ions: affinity modification study.
AB  - Sequence-specific alkylation of dsDNA with pyrimidine oligonucleotides bearing an
      alkylating group at the 3' and 5' terminal phosphates, or both, has been
      investigated. At pH 5.4, sequence-specific modification of guanosines of the DNA
      in the vicinity of the target purine-pyrimidine sequence occurs. The reactive
      group at the 5' terminus of the oligonucleotides attacks guanosines in the purine
      strand of the target DNA. The reactive group at the 3' end can interact with
      guanosines in both strands of the DNA. Bifunctional reagents can alkylate both
      strands of the DNA simultaneously. At pH 4 in the presence of magnesium ions, the
      oligonucleotide derivatives can form imperfect complexes with sequences
      homologous to the target sequence and alkylate the DNA at the corresponding
      positions.

PMID- 8155978
TI  - Internalization of oligodeoxyribonucleotides by Vibrio parahaemolyticus.
AB  - The bacterium Vibrio parahaemolyticus was tested for its ability to internalize
      unmodified as well as modified DNA oligomers without attempting to permeabilize
      the cells. These experiments were conducted to establish whether it may be
      feasible to employ antisense oligomers for control of gene expression in Vibrio
      species without heat-shocking or electroporating the cells. The bacterium was
      found to bind radiolabeled synthetic oligodeoxyribonucleotides that were added to
      culture media. Incorporation of a phosphorothioate oligomer into subcellular
      regions was determined following cellular fractionation. The phosphorothioate was
      recovered primarily from the periplasm and peptidoglycan layer of the bacterium;
      however, a significant fraction was recovered from the bacterial cytosol. The
      extent of uptake depended on both the concentration of oligomer as well as
      culture medium selected. A maximum of 2.1 x 10(6) oligomers/cell was achieved
      when a 12-mer phosphorothioate oligomer (10 microM) was added to bacterial
      cultures in an artificial seawater (Instant Ocean) medium. Several terminally
      modified oligomers were found to become associated with bacterial cells, albeit
      less efficiently than the phosphorothioate. None of the oligomers tested was
      toxic to the bacteria at 0.1 microM, and the phosphorothioate was only marginally
      toxic at 10 microM. Stability of the oligomers in extracellular and cell
      associated fractions was evaluated by PAGE; even after 8 hr of incubation intact
      phosphorothioate oligomer could be found in both components.

PMID- 8155979
TI  - Systemic administration of a phosphorothioate oligonucleotide with a sequence
      complementary to p53 for acute myelogenous leukemia and myelodysplastic syndrome:
      initial results of a phase I trial.
AB  - A synthetic phosphorothioate oligonucleotide was administered systemically to
      five patients with either relapsed or refractory acute myelogenous leukemia
      (AML), or myelodysplastic syndrome (MDS). Patients received a 10-day continuous
      intravenous infusion of this compound, which is complementary to p53 mRNA. No
      major toxicity attributable to a dose of 0.05 mg/kg/hr was observed. A range of
      approximately 9 to 18% of the administered dose was recovered in the urine as
      intact oligonucleotide. Evaluation of malignant cells recovered from bone marrow
      and peripheral blood at intervals before, during, and after treatment reveals no
      enhanced growth potential following oligonucleotide administration. Hence, a
      phosphorothioate oligonucleotide complementary to p53 mRNA can be administered at
      this dose level to humans without major toxicity. Higher doses need to be
      evaluated for toxicity and potential clinical efficacy.

PMID- 8155980
TI  - Effect on embryos of injection of phosphorothioate-modified oligonucleotides into
      pregnant mice.
AB  - Phosphorothioate-modified oligonucleotides were injected into pregnant female
      mice to assess the effect on developing embryos. Injections were carried out
      during two different time periods, one when embryos were in preimplantation
      stages of development (about 3.5 days of development) and the other after
      implantation, when both a fetus and placenta are present (from days 9.5 to 11.5
      of development). Three different phosphorothioate-modified oligonucleotides were
      injected. One, which had a sequence not present in the mouse genome, was used to
      ask whether nonspecific toxic or teratogenic effects on embryos result from
      treatment of the mother. A second was complementary to the mRNA of the testis
      determining factor gene Sry and was used to ask whether a specific developmental
      pathway (i.e., sex determination) could be disrupted in embryos in vivo. The
      third was the complement of the anti-Sry sequence. None of these oligonucleotides
      reduced the frequency of successful pregnancy after mating or the average litter
      size from that observed in controls animals. Furthermore, examination of 291 pups
      or fetuses from all oligonucleotide-injected pregnant females revealed no
      developmental defects regardless of which sequence was used. It is concluded that
      injection of phosphorothioate-modified oligonucleotides into pregnant females
      according to the protocols described here is not toxic or teratogenic to embryos
      in a nonspecific way. Also, anti-Sry oligonucleotides did not influence sex
      determination in embryos, although there are several possible explanations for
      this.

PMID- 8155981
TI  - Regulatory considerations for evaluating the pharmacology and toxicology of
      antisense drugs.
AB  - This article focuses on pharmacology and toxicology data that should be included
      in an Investigational New Drug Application (IND), a request to use an
      investigational drug in clinical trials. In general, pharmacology and toxicology
      testing programs for antisense compounds are held to the same regulatory
      standards applied to other new therapeutic classes. Biological properties of
      oligonucleotide therapeutics are mentioned where they may pertain to clinical
      safety issues. Nonclinical data submitted to the IND should characterize the
      pharmacology, disposition, and toxicology of a new drug; these data form the
      basis for clinical risk assessment. Concomitant evaluation of pharmacokinetics
      allows for better interpretation of in vivo studies and increased accuracy of
      dose extrapolation to humans. Recommendations for nonclinical drug development
      will be modified as new information regarding the biological properties of
      oligonucleotides becomes available.

PMID- 8155982
TI  - Regulatory concerns for the chemistry, manufacturing, and controls of
      oligonucleotide therapeutics for use in clinical studies.
AB  - It is important to remember that while a new class of therapeutic agents like
      oligonucleotides may introduce novel concerns, the basic regulatory issues
      regarding the chemistry, manufacturing, and controls of drug substances and drug
      products must be addressed. This article focuses on information that should be
      included in an Investigational New Drug Application (IND), a request to use an
      investigational drug in clinical studies. The regulatory challenge presented with
      oligonucleotide therapeutics is to prove the identity of the oligonucleotide, and
      demonstrate its quality, purity, and strength/potency using both those
      characteristics that are the same as all other drugs, as well as those that are
      unique. Most of the discussion will concern issues that are unique to
      oligonucleotides, or those topics that deserve more detailed attention than would
      be needed for more typical small molecule drugs. Regulatory issues will need to
      be evaluated so that safety concerns are addressed while not imposing undue
      burden on the sponsors of investigational drugs.

PMID- 8155983
TI  - Progress in antisense research and development.

PMID- 8155984
TI  - A review of the capabilities of ICP-MS for trace element analysis in body fluids
      and tissues.
AB  - ICP-MS is a powerful analytical technique for the determination of trace and
      ultra-trace elements in biological materials. Results are given of the analysis
      of human serum and of several biological reference materials (bovine liver, milk
      powder, wheat flour and pig kidney). Because concentrations of many trace metals
      of interest in these materials are low, dilution should be kept as limited as
      possible, although concentrations of certain concomitant elements (e.g. Na, K)
      can be high enough to cause significant suppression or enhancement of the ion
      signal. The result is that the dissolution procedure becomes a critical step in
      the analysis. Microwave digestion, wet digestion with several acids (HNO3, HClO4,
      HF) and simple dilution are compared with each other. In addition, three possible
      approaches to overcome these problems are discussed, namely the internal
      standardization method, the standard addition method and the isotope dilution
      method. Furthermore, ICP-MS is also more susceptible than initially expected to
      isobaric interferences arising from the plasma, the acids used in the sample
      preparation or the sample itself. These interferences are generally less
      important above a mass number of 80. Nevertheless, several researchers have
      investigated the possibility of removing the trace metals from the matrix or of
      using correction formulae based on the isotopic abundances of the elements. Some
      of these are evaluated. The need for identifying and quantifying chemical
      species, not just the elements, is well recognized. One of the reasons why
      elemental determination may not suffice is that different species of the same
      element may have a different chemical and toxicological behaviour. Arsenic
      (As(III), As(V)) and mercury (organomercury) are typical examples.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155985
TI  - Zinc metabolism in fasted rats.
AB  - The effects of short-term starvation on serum and tissue levels of zinc,
      metallothionein (MT), and the activity of alkaline phosphatase (EC 3.1.3.1, ALP)
      were investigated with 6-month-old rats. The rats were fed a diet with adequate
      zinc (92mg/kg of Zn, 1.12% phytic acid) before they were starved for 0h
      (control), 12h, 24h, and 36h and then killed by decapitation. Fasting was
      accompanied by typical changes in serum parameters such as reduced glucose and
      protein concentrations, elevated ketogenesis, and a rapid breakdown of liver
      glycogen. Fasting did not alter serum zinc levels, but it did lead to a
      significant elevation in the percent of unsaturated serum-zinc binding capacity.
      Liver concentrations of zinc and MT, based both on fresh and dry weight, were
      increased throughout starvation. However, total liver zinc was reduced by up to
      23% in response to fasting and total liver MT was slightly elevated. The
      increased concentrations of liver zinc and MT are, therefore, mainly a
      consequence of reduced liver weight. A part of the liver zinc, however, was bound
      to newly synthesized MT to prevent greater zinc loss. Starvation evoked no
      altered mucosa MT levels. Changes in kidney zinc and kidney medulla MT caused by
      starvation were small and not significant. In contrast to this observation some
      variation of kidney cortex MT was apparent. Starvation produced a permanent
      reduction of the serum and intestinal activity of ALP. In the liver and the
      medulla of the kidneys no significant differences of ALP activity could be
      observed. However, kidney cortex ALP was induced after 36h of fasting.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8155986
TI  - Effects of different levels of dietary selenium and vitamin E on the humoral
      immunity of rats.
AB  - The aim of the present study was to investigate whether the level of selenium and
      selenium/vitamin E supply influences the humoral immunity of rats. In order to
      detect the effect of Se supply and age, 36 weaned Sprague-Dawley rats divided
      into two equal groups were killed after 22 or 45 experimental days by
      decapitation (Exp. I). In Exp. II 9 groups of 10 rats each were exposed to each
      combination of deficient, normal or excessive selenium with a vitamin E supply
      and killed after 44 days. The basic (deficiency) diet which was the same in both
      experiments contained 0.04mg Se and 8mg vitamin E per kg dry matter. The
      supplementation per kg diet was 0 or 0.2mg Se and 30mg vitamin E in Exp. I and 0,
      0.2 or 1mg Se and 0, 30 or 200mg vitamin E in Exp. II. The concentration of
      selenium in serum, liver and spleen samples and the activity of glutathione
      peroxidase, which were determined to define the selenium status of the animals,
      corresponded well to the required supply situation. The immunoglobulins of type
      IgA, IgM and IgG with the subtypes IgG1, IgG2a, IgG2b and IgG2c were measured by
      immunoelectrophoresis. In both experiments selenium deficiency decreased the
      values of the IgG groups only nominally, IgA was not changed. IgM was
      significantly reduced, especially with prolonged selenium deficiency and
      simultaneous vitamin E deficiency. An excessive selenium supply compensated to a
      great extent for the effects of vitamin E deficiency on IgG and IgA.

PMID- 8155987
TI  - Catalytic photometric determination of cobalt in the urine of children with
      increased arterial pressure.
AB  - The concentration of the microelement cobalt in the urine of healthy children and
      of children with increased arterial pressure was studied. The values of the
      cobalt content in the urine of clinically healthy children were 0.22 +/- 0.06
      mumol/l in boys and 0.21 +/- 0.11 mumol/l in girls, which were taken as normal,
      while the values in children with increased arterial pressure were 0.39 +/- 0.17
      mumol/l in boys and 0.28 +/- 0.06 mumol/l in girls, which are considered to be
      increased. These results were explainable by incomplete assimilation and
      excretion of a great part of the cobalt in the urine of children with elevated
      arterial pressure (AP).

PMID- 8155988
TI  - Activity of antioxidative enzymes in erythrocytes and concentration of selenium
      in plasma related to mercury exposure.
AB  - The activity of catalase and glutathione peroxidase (GSH-Px) in erythrocytes and
      concentration of selenium in plasma and mercury in whole blood, plasma, and urine
      were analyzed in 36 individuals occupationally exposed to mercury vapor, in 14
      individuals with skin hypersensitivity to inorganic mercury, and in 17
      individuals with subjective symptoms alleged to result from dental amalgam
      fillings. The control group consisted of 39 individuals with amalgam fillings,
      but no occupational exposure to mercury. Selenium in plasma was determined by
      GFAAS with Zeeman background correction. After exclusion of individuals with
      reported intake of selenium supplement the median plasma selenium concentration
      in the group with occupational exposure to mercury was 1.24 mumol/L, in the
      allergy group 1.22 mumol/L, in the amalgam group 1.25 mumol/L, and in the control
      group 1.22 mumol/L. The activities of catalase and GSH-Px were similar in all
      groups. However, in females lower GSH-Px activity was found in the amalgam group
      compared with females in the control group. GSH-Px activity in smokers was
      slightly lower than in non-smokers. No correlations were found between
      concentration of selenium or mercury in plasma and activity of glutathione
      peroxidase or catalase in erythrocytes.

PMID- 8155989
TI  - Daily dietary intake of copper and zinc by several population groups in Belgium:
      preliminary reports.
AB  - Atomic absorption spectrometry is used to determine copper and zinc content of
      several duplicate meals consumed by different population groups in the Antwerp
      region (Belgium). Daily elemental intake, beverages not included, is calculated
      and proven to be below the recommended daily allowances (National Academy of
      Sciences, USA), except for copper intake by macrobiotics. Values obtained in this
      study are compared with scarce data on intake by similar groups in other
      countries.

PMID- 8155990
TI  - Platelet selenium as indicator of wheat selenium intake.
AB  - The effect of an increased intake of wheat selenium (Se) on platelet Se, serum
      Se, whole-blood Se, and glutathione peroxidase (GSH-Px) levels was investigated
      in 14 healthy Norwegian females (age 21-53 years). The intake of 60 micrograms Se
      per day as wheat Se, for six weeks, significantly increased the platelet Se (mean
      +/- SEM) from 9.1 +/- 1.1 mumol/L to 11.4 +/- 0.9 mumol/L, the serum Se from 1.43
      +/- 0.18 mumol/L to 1.63 +/- 0.25 mumol/L, and the whole blood Se from 1.77 +/-
      0.18 mumol/L to 2.01 +/- 0.18 mumol/L. The increase in percent of initial Se
      values was twice as high for platelets as for serum and whole blood. The GSH-Px
      levels were not altered during the experiment. Platelet Se was not significantly
      correlated to the Se intake initially. At the end of the experimental period, the
      Se in platelets reflected the total Se intake, but not with a simple linear
      correlation. No significant correlation between the total Se intake and the Se
      concentration in whole blood or serum was found.

PMID- 8155991
TI  - Simultaneous multi-element determination of selected elements in dog urine by
      direct current plasma-atomic emission spectrometry.
AB  - Urine samples from dogs were analyzed for 15 important elements (Ca, Cd, Co, Cr,
      Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, V, and Zn) by using wet-ashing and simultaneous
      DCP atomic emission spectrometry. As K, Na and P influence the spectral emission
      of elements to be determined, matrix-matching was applied to ensure accurate
      metal determinations. The method was checked by analyzing standard reference
      materials of urine. The values found were generally in agreement (accuracy within
      100 +/- 10%) with the certified values. Short- and long-term stabilities of the
      instrument for the elements determined ranged from 0.4 to 2.2% and from 1.2 to
      6.9%, respectively. Simultaneous multi-element determination gives increased
      information on trace- and minor elements in urine. In the present study DCP
      atomic emission spectrometry is successfully applied for this purpose.

PMID- 8155993
TI  - About "changes in zinc metabolism after burns".

PMID- 8155992
TI  - Concentrations of calcium, magnesium, zinc and copper in relation to free fatty
      acids and cholesterol in serum of atherosclerotic men.
AB  - The concentrations of calcium, magnesium, zinc, copper, free fatty acids and
      total, HDL- and LDL-cholesterol in the sera of atherosclerotic men were
      determined. The subjects with femoral atherosclerosis were divided into two age
      groups: 35-59 years (N = 8, I) and 60-75 years (N = 8, II). The LDL-cholesterol
      concentration was increased in the elderly atherosclerotic group. Lower
      concentrations of calcium and magnesium, a higher concentration of copper and
      decreased Ca/Cu, Mg/Zn, Mg/Cu and Zn/Cu ratios were found in atherosclerosis I as
      compared to controls of the same age. High and positive correlations for Cu vs.
      total cholesterol and LDL-cholesterol (r > 0.89), but low correlation for Cu vs.
      HDL-cholesterol (r = 0.61) were calculated in atherosclerosis I, and negative
      correlations for free fatty acids vs. Ca and Mg (-r > 0.77) in atherosclerosis
      II.

PMID- 8155994
TI  - Selective regulation of chemotactic lymphokine production by monocytes and
      macrophage cell line cells.
AB  - Effects of lipopolysaccharides (LPS) on the production of chemotactic lymphokines
      for eosinophils and monocytes (ECF and MCF) from antigen- or mitogen-stimulated T
      cells were examined. Supernatants from monocytes stimulated with various LPS
      regulated concanavalin A (Con A)- and purified protein derivative (PPD)-induced
      ECF or MCF production. The regulation varied with LPS used for monocyte
      stimulation. The supernatant from monocytes stimulated with LPS from Escherichia
      coli, J-5 strain, selectively potentiated ECF production, whereas that from
      Salmonella minesota potentiated MCF production. In contrast, supernatant from
      monocytes stimulated with LPS from Salmonella typhimurium potentiated both ECF
      and MCF production, whereas that from Vibrio cholerae failed to potentiate
      production. The supernatants from monocytes stimulated with lipid A of S.
      typhimurium, S. minesota, and E. coli, however, failed to potentiate ECF and MCF
      production. The potentiating activity for each lymphokine was recovered from
      fractions ranging in molecular weight between 10 and 20 kD. Further purification
      with isoelectric electrophoresis revealed that the potentiating activity for the
      production of chemotactic lymphokine for eosinophils has a pI value of about 4-5,
      and that the activity for MCF production is detected in two fractions of pI about
      5-6, and 7-8. Macrophage lineage cell line cells, such as THP-1 and U-937, also
      release similar factors after differential stimulation.

PMID- 8155995
TI  - Heterogeneous eosinophils of allergic rhinitis in chemotactic response.
AB  - Chemotactic responses of eosinophils from patients with allergic rhinitis to 5
      STO-2-derived eosinophil chemotactic factors (ECF), IL-3, IL-5 and GM-CSF were
      examined. The patients were divided into two groups: patients with perennial
      allergic rhinitis sensitive to Dermatophagoides farinae and those with seasonal
      allergic rhinitis sensitive to Japanese cedar pollen. There was no essential
      difference between chemotactic response of eosinophils from the former to STO-2
      derived ECF and that from healthy individuals. However, eosinophils from patients
      with seasonal allergic rhinitis failed to respond to one of the STO-2-derived
      ECFs, ECF-P19. Before and after nasal antigen provocation, no change occurred in
      the chemotactic profiles. Furthermore, we found that eosinophils from both types
      of patients with allergic rhinitis responded not only to IL-3 and GM-CSF but also
      to IL-5 unlike those of healthy individuals.

PMID- 8155996
TI  - Mechanism of eosinophil infiltration in the patient with subcutaneous
      angioblastic lymphoid hyperplasia with eosinophilia (Kimura's disease). Mechanism
      of eosinophil chemotaxis mediated by candida antigen and IL-5.
AB  - Kimura's disease is a chronic granulomatous disease of unknown etiology. Although
      eosinophilia is one of the characteristic features in this disease, little is
      known about the mechanism of eosinophilia. In the present study it was
      demonstrated that interleukin-5 (IL-5) was produced and released from the site of
      a granuloma and lymph nodes after stimulation with candida antigen. It was also
      shown that peripheral blood eosinophils from patients with Kimura's disease
      contained a large proportion of hypodense eosinophils and that their viability
      was prolonged. These results strongly suggest that locally produced IL-5 induced
      by candida antigen contributes to the eosinophilia in this disease.

PMID- 8155997
TI  - Ultrastructural analysis of peripheral eosinophils in children with bronchial
      hyperresponsiveness.
AB  - To investigate the condition of peripheral eosinophils in patients with bronchial
      hyperresponsiveness, we examined density distribution profiles and ultrastructure
      of peripheral eosinophils obtained before and after exercise challenge test.
      Following exercise challenge test, the number of hypodense eosinophils (< 1.0825
      g/ml) was significantly higher in the EIA-positive than in the EIA-negative
      subjects. Regarding ultrastructural analysis, the ratio of the area of specific
      granules to the area of cytoplasm (SG/C) per cell was significantly higher in the
      EIA-negative than in the EIA-positive patients. The ratio of the degranulated
      area to the area of cytoplasm (D/C) per cell was significantly higher in the EIA
      positive than in the EIA-negative subjects. These data suggested that activation
      of eosinophils in the patients with bronchial hyperresponsiveness occurs during
      the preinflammatory phase.

PMID- 8155998
TI  - Chemotactic heterogeneity of eosinophils in Kimura's disease.
AB  - We evaluated the chemotactic heterogeneity of eosinophils in Kimura's disease.
      Patients with Kimura's disease were divided into two groups according to their
      clinical findings: one group had no other symptoms (KD), and another was
      accompanied with atopic dermatitis (KD + AD). The chemotactic response of
      eosinophils from two groups to 5 eosinophil chemotactic factors (ECF) derived
      from STO-2, an established T cell line. Eosinophils from KD were attracted only
      by ECF-PI5 and PI6 but not by ECF-PI7, PI8 and PI9. On the other hand,
      eosinophils from KD + AD responded to all 5 ECF. Eosinophils were further
      fractionated into normodense and hypodense eosinophils, and assessed for their
      chemotactic response. We thus found that there was little essential difference in
      their chemotactic responses to STO-2-derived ECF except ECF-PI9, though random
      migration of hypodense eosinophils was enhanced. The hypothesis that hypodense
      eosinophils are in the activated form was not always true, especially in the
      chemotactic response to ECF.

PMID- 8156000
TI  - Degranulation from human eosinophils stimulated with C3a and C5a.
AB  - It is unclear what actually induces eosinophil degranulation in vivo. We examined
      eosinophil cationic protein (ECP) release from normal human eosinophils (Eos) in
      response to C3a and C5a. C3a and C5a induced remarkable ECP release when Eos were
      preincubated with cytochalasin B. ECP release induced by C3a or C5a was greater
      than that induced by PAF at a concentration of 10(-7) M. The ED50 for ECP release
      was 3 x 10(-8) M and 3 x 10(-9) M for C3a and C5a, respectively. C3a or C5a
      elicited a rapid and transient rise in [Ca2+]i. These results suggest that C3a
      and C5a may contribute to hypersensitivity diseases by inducing eosinophil
      degranulation.

PMID- 8155999
TI  - Eosinophil chemiluminescence response to cytokines and opsonized zymosans in
      atopic dermatitis.
AB  - Chemiluminescence (CL) responsiveness of eosinophils (Eos) to zymosan particles
      coated with either IgG, C3 or both and eosinophilopoiesis-modulating cytokines
      was investigated in patients with atopic dermatitis (AD), and an attempt was made
      to correlate these CL responses with serum levels of eosinophil cationic protein
      (ECP) which increased in response to the extent of AD severity, but not blood
      eosinophil counts. A high degree of positive correlation existed between serum
      levels of ECP and either IgG containing opsonized zymosan- or interleukin-5 (IL
      5)-induced CLs. The CL values induced by these two stimuli appeared to be
      directly correlated with the intensity of each ligand-linked receptor expression.
      These results suggested that Fc gamma RII-and/or IL-5R-mediated eosinophil
      activation at the site of lesional skins might implicate in deterioration of
      cutaneous inflammation, and consequently cause an elevation of serum levels of
      ECP in AD.

PMID- 8156001
TI  - Transcriptional regulation of the human eosinophil peroxidase genes:
      characterization of a peroxidase promoter.
AB  - The molecular basis for commitment of progenitors to the eosinophil lineage and
      mechanisms by which eosinophil-specific genes are expressed and regulated during
      differentiation is unknown. Expression of eosinophil peroxidase (EPO) is
      restricted to the eosinophil lineage. To understand the mechanisms involved in
      transcriptional regulation of EPO gene expression, we cloned the region of the
      EPO gene upstream of the transcriptional start site and analyzed the cis-acting
      elements required for EPO promoter activity in an eosinophil-inducible leukemic
      cell line, HL60-C15. The -1.5 kb EPO-pXP2 promoter construct reproducibly
      expressed > 120-fold more luciferase activity than did promoterless pXP2, and a
      12-fold decrease in promoter activity was obtained when sequences between -122
      and -45 bp were deleted. To further characterize regulatory sequences important
      for promoter activity, we performed linker-scanning analysis on the -122 to -45
      bp region and identified a number of positively and negatively acting elements in
      the promoter.

PMID- 8156002
TI  - Reconstitution of the functional interleukin-5 receptor: the cytoplasmic domain
      of alpha-subunit plays an important role in growth signal transduction.
AB  - The receptor for interleukin-5 (IL-5) is composed of two distinct subunits, alpha
      and beta. The cDNAs that encode the mouse and human alpha-subunit were
      transfected into the mouse IL-3-dependent cell line, FDC-P1 expressing the mouse
      beta-chain intrinsically. The resulting transfectants became responsive to human
      and mouse IL-5, respectively. Using the mutant alpha-subunits, we found that the
      alpha-subunit as well as the beta-subunit participated in IL-5-mediated growth
      signal transduction. The FDC-P1 transfectants expressing the alpha-subunit which
      lacks its whole cytoplasmic domain did not respond to IL-5, though the
      interaction of the mutant alpha- and beta-subunits was not impaired. The
      transfectants expressing the alpha-subunit which lacks the C-terminal half of its
      cytoplasmic domain proliferated in the presence of IL-5. These results indicate
      that the transmembrane-proximal cytoplasmic portion of the alpha-subunit plays an
      important role in IL-5-mediated growth signal transduction.

PMID- 8156003
TI  - Interferon-gamma induces interleukin-3 release from peripheral blood eosinophils.
AB  - Interferon-gamma (IFN-gamma) upregulates eosinophil effector functions and
      prolongs the in vitro survival of eosinophils. We examined the possible capacity
      of IFN-gamma to stimulate eosinophils to produce eosinophil-activating cytokines.
      Eosinophils purified from mild atopic volunteers were cultured with 100 U/ml IFN
      gamma. Viability of eosinophils was counted and supernatants were tested for the
      presence of cytokines by neutralization of eosinophil viability-enhancing
      activity with specific antibodies to IFN-gamma, interleukin-5 (IL-5), IL-3, or
      granulocyte-macrophage colony-stimulating factor (GM-CSF). IFN-gamma-enhanced
      eosinophil viability was up to 95% on the 4th day of culture. Pretreatment with
      anti-IL-3 antibody partially blocked the IFN-gamma-enhanced eosinophil survival.
      IFN-gamma-stimulated eosinophil supernatants had eosinophil survival. IFN-gamma
      stimulated eosinophil supernatants had eosinophil viability-enhancing activity
      that was blocked by pretreatment not only with anti-IFN-gamma but also with anti
      IL-3. Antibodies to IL-5 or GM-CSF did not have the blocking effect. To further
      confirm the production of IL-3 by eosinophils, we performed reverse transcription
      polymerase chain reaction (RT-PCR) for IL-3 messenger RNA (mRNA) in IFN-gamma
      stimulated eosinophils. Significant IL-3 mRNA expression in eosinophils was
      observed at 6 h of incubation with IFN-gamma. These results suggest that IFN
      gamma stimulates the autocrine function of eosinophils and may play an important
      role in allergic inflammation.

PMID- 8156004
TI  - Regulation of interleukin-5 production by interleukin-4, interferon-alpha,
      transforming growth factor-beta and interleukin-6.
AB  - Normal lymphocytes produce IL-5 with PHA and PMA stimulation. In this system, IL
      5 production was enhanced by IL-4 and was inhibited by IFN alpha, TGF beta and IL
      6.

PMID- 8156005
TI  - Induction of expression of adhesion molecules on an eosinophilic cell line (EoL
      1) by the supernatant of lymphocytes stimulated with specific allergen from
      asthmatic patients.
AB  - Recently, adhesion molecules have been considered to play an important role in
      inflammatory processes in bronchial asthma. To extend our understanding of the
      high-intensity expression of adhesion molecules (CR3, LFA-1 alpha, LFA-1 beta,
      ICAM-1) on hypodense eosinophils, which was observed in our previous study, we
      examined whether the supernatant of lymphocytes from mite-allergic asthmatic
      patients is involved in adhesion molecule expression using an eosinophilic cell
      line (EoL-1). These characteristics of adhesion molecule expression were induced
      by the supernatant of lymphocytes obtained from mite-allergic asthmatic patients
      cultured with specific allergen as well as a combination of recombinant cytokines
      (IL-3, GM-CSF, IL-5). Thus, we could conclude that some lymphokines produced by
      specific allergen in asthma might be involved in the high-intensity expression of
      adhesion molecules on hypodense eosinophils in asthma or allergic disorders.

PMID- 8156006
TI  - Effect of platelet-activating factor and platelet factor 4 on eosinophil
      adhesion.
AB  - The effect of platelet-activating factor (PAF) and platelet factor 4 (PF4) on the
      adhesion of isolated human eosinophils or eosinophilic cell lines (EoL-1, EoL-3)
      was examined. Both PAF and PF4 augmented eosinophil adhesion to plates coated
      with AB plasma or recombinant soluble intercellular adhesion molecule-1 (r-sICAM
      1). These findings suggest that PAF and PF4 not only modulate chemotactic
      activity of eosinophils but also intensify the function of eosinophil adhesion.
      Since PAF and PF4 induce the expression of adhesion molecules (LFA-1 alpha, LFA-1
      beta, CR3) on eosinophils, we could conclude that PAF or PF4 are closely related
      to eosinophil accumulation not only as chemotactic agents but also as
      augmentative agents for eosinophil adhesion through involvement in functional
      eosinophil adherence as well as surface expression of adhesion molecules on
      eosinophils.

PMID- 8156007
TI  - A novel method of counting eosinophils in nasal secretion of allergic rhinitis by
      hemocytometric method.
AB  - The test for eosinophilia in nasal secretion is a useful tool for the diagnosis
      of allergic rhinitis. However, the nasal smear test which is commonly used is a
      subjective and nonquantitative evaluation. In this paper we describe a novel
      simple, objective and quantitative method in which mucin cluster in collected
      nasal secretion or lavage is solubilized with dithioerythritol, following which
      the number of eosinophils per unit volume of nasal secretion or the ratio of
      eosinophil to total leukocyte can be successfully counted in a blood cell
      counting chamber by using a hemocytometric method.

PMID- 8156008
TI  - Effects of eosinophilotropic cytokines on differentiation of an eosinophil cell
      line, YY-1.
AB  - Differentiation of an eosinophilic cell line, YY-1, was induced by treatment with
      0.3 mM butyric acid (BA). The effects of eosinophilotropic cytokines, such as IL
      3, IL-5, and GM-CSF on BA-induced differentiation, especially in the chemotactic
      response to ECF, was examined. Five STO-2-derived ECFs, IL-5, C5a, and fMLP were
      used as eosinophil chemoattractants. The effects of the cytokines on the
      chemotactic response of YY-1 greatly differed according to the ECF used. It was
      thus suggested that heterogeneity in the chemotactic response of eosinophils
      depends on the cytokines which act on eosinophils during differentiation.

PMID- 8156009
TI  - A review on Fc epsilon RI on human epidermal Langerhans cells.
AB  - In order to show the surface expression of Fc epsilon RI on human epidermal
      Langerhans cells (LC), we examined monomeric IgE binding to LC. We demonstrated
      that the majority of epidermal LC were able to bind monomeric IgE. IgE binding to
      LC could neither be prevented by preincubation of the tissue with monoclonal
      antibodies (mAb) against either Fc epsilon RII/CD23 or Fc gamma RII/CD32, nor by
      the addition of lactose, but could be entirely abrogated by preincubation with
      the anti-Fc epsilon RI mAb 15-1. These data show that epidermal LC express Fc
      epsilon RI molecules.

PMID- 8156010
TI  - A B cell lymphoma line, BALL-1 stimulates T cells to produce a unique eosinophil
      chemotactic factor.
AB  - Human mononuclear leukocytes (MNL), probably OKT4-positive T cells, produced an
      eosinophil chemotactic factor (ECF) when they were cocultured with irradiated
      BALL-1, a B cell lymphoma line. Treatment of MNL, with anti-IL-2 antibody failed
      to suppress BALL-1-induced ECF production. Periodate-lysine-paraformaldehyde
      fixed but not acetone- and ethanol-fixed BCLL induced evident ECF production.
      These results suggested that some cell surface molecules play a role in the
      induction of ECF production. Isoelectric point of BALL-1-induced ECF was around
      pH7, whereas that of IL-2-induced ECF was around pH 5. The molecular weight of
      BALL-1-induced ECF was between 10 and 30 kD. Although a combination of MoAb
      against IL-3, IL-5, and GM, CSF suppressed the activity of IL-2-induced ECF, it
      failed to suppress that of BALL-1-induced ECF. Furthermore, BALL-1-induced ECF
      suppressed fMLP-induced respiratory bursts of eosinophils, while IL-2-induced ECF
      failed. We propose that at least one reason for eosinophil infiltrate into the
      stroma of tumors is that the tumor cells stimulate T cells to produce BALL-1
      induced ECF, and the eosinophils attracted by the ECF exhibit different functions
      from those by other ECF.

PMID- 8156011
TI  - Fire baby.

PMID- 8156013
TI  - Strategies for containing health care costs.

PMID- 8156012
TI  - Breastfeeding and the environment. A policy brief from Wellstart International.

PMID- 8156014
TI  - More than twenty years ago, I founded a midwifery service.

PMID- 8156015
TI  - Aaron steps out: a cautionary tale.

PMID- 8156016
TI  - Massachusetts woman wins historic malpractice award for coerced cesarean section.

PMID- 8156017
TI  - Healing sexual pain through natural childbirth.

PMID- 8156018
TI  - What are your recommendations as to when to start a breastfed baby on solids?

PMID- 8156019
TI  - Both routes to midwifery training needed.

PMID- 8156020
TI  - Health care reform.

PMID- 8156021
TI  - Interview with Margre Brak, midwife. Interview by Ina May Gaskin.

PMID- 8156022
TI  - Interview with Janette Hurley, MD. Interview by Ina May Gaskin.

PMID- 8156023
TI  - Early termination of pregnancy.

PMID- 8156024
TI  - Costing of a salt iodine monitoring laboratory in India.
AB  - BACKGROUND: Iodine deficiency disorders (IDD) are an important public health
      problem in India and can be prevented by fortifying common salt with iodine. For
      the iodation programme to be effective, it is necessary to monitor the iodine
      content of salt. The National Iodine Deficiency Disorders Control Programme
      recommends that one salt iodine monitoring laboratory should be set up in each
      district. We calculated the cost of setting up such a laboratory in the year
      1993. METHODS: We estimated that approximately 6000 samples of salt would be sent
      annually by health workers to the district laboratory as part of the routine
      report system. We calculated the capital cost of the laboratory to include land,
      buildings and equipment. The recurrent costs included salaries, chemicals and
      reagents, and maintenance assuming a uniform discount of 10%. RESULTS: A total of
      Rs 81,550 would be needed for one such laboratory annually, of which Rs 73,500
      (89%) would be recurrent costs. This comes to Rs 13.60 per sample tested or 5
      paise per head per year in a district with an average population of 1.7 million.
      If the building is already available and the staff in position only need to be
      trained, then Rs 16,040 per year (equipment, chemicals and operating costs) would
      be required. This comes to 1 paise per head per year. CONCLUSIONS: Setting up a
      salt iodine monitoring laboratory, a vital component for the salt iodation
      programme, has modest cost implications, especially if the building and staff
      already exist. This is likely to be the case in most of the districts.

PMID- 8156025
TI  - The use of ivermectin for scabies.
AB  - BACKGROUND: Ivermectin, a modified avermectin, is widely known to be an
      ectoparasiticidal agent in animals but its effect on human ectoparasites is not
      known. METHODS: As a part of a chemotherapy trial with ivermectin against
      Wuchereria bancrofti microfilaraemia, two males with clinical scabies were
      studied. Three skin scrapings were taken from the lesions of each of the cases
      and examined with potassium hydroxide solution for the presence of eggs, larvae
      or adult mites. RESULTS: Following a single oral dose of ivermectin at either 100
      micrograms or 20 micrograms/kg body weight both the itching and eruptions were
      reduced and the lesions healed after 14 days of treatment. Skin scrapings taken
      on days 7 and 30 after administering the drug did not reveal any mites. However,
      the lesions reappeared after 3 months. CONCLUSION: The beneficial results on the
      healing of scabetic lesions following ivermectin therapy indicates that the drug
      may have a scabicidal effect. Reappearance of the lesions may have been due to an
      inadequate dose. This emphasizes the need for future controlled trials on the
      efficacy of ivermectin against human scabies infection. If proven, this may be an
      additional advantage in mass chemotherapy campaigns, when there is co-existence
      of filariasis, intestinal helminthiasis and scabies.

PMID- 8156027
TI  - Additives in children's medicines.

PMID- 8156026
TI  - Management of fulminant hepatic failure.

PMID- 8156028
TI  - Breast cancer--do we need to change the model?

PMID- 8156029
TI  - A tale of two syndromes X.

PMID- 8156031
TI  - Recognizing depression.

PMID- 8156030
TI  - Congenital diaphragmatic hernia--correction in utero.

PMID- 8156032
TI  - Antihypertensive therapy in the elderly.

PMID- 8156033
TI  - Neonatal intensive care in India.

PMID- 8156034
TI  - Doctors' incomes: private or public?

PMID- 8156035
TI  - The Supreme Court on capitation fees.

PMID- 8156036
TI  - Platelet function disorders in north India.
AB  - BACKGROUND: Platelet function disorders are a fairly common cause of bleeding
      manifestations. Although their relative types and incidence are well documented,
      data from India are lacking. METHODS: Between 1970 and 1991, we studied the
      clinical and laboratory features of 144 north Indian patients who presented to
      our hospital with a bleeding diathesis in whom coagulation disorders, von
      Willebrand's disease and a history of drug ingestion were absent. RESULTS:
      Isolated platelet factor 3 availability defect was the commonest (56 cases)
      followed by the thrombasthenias (49 cases), arachidonic acid pathway defect (26
      cases), storage pool disease (8 cases) and the Bernard-Soulier syndrome (3
      cases). Isolated platelet factor 3 deficiency was rare (2 cases). Two varieties
      of thrombasthenia were seen--the classical Glanzmann's (13 cases) and
      thrombopathic (36 cases). The latter was characterized by absent or sub-normal
      platelet aggregation with agonists along with a reduced (to less than 50% of
      normal) total platelet factor 3 content. This has not been reported from western
      countries. Patients with classical Glanzmann's thrombopathic thrombasthenia with
      absent platelet aggregation and isolated platelet factor 3 deficiency were severe
      bleeders. Their family history suggested an autosomal recessive transmission in
      Glanzmann's and thrombopathic thrombasthenia and a possible autosomal dominant
      transmission in isolated platelet factor 3 availability defect and isolated
      platelet factor 3 deficiency. CONCLUSION: The frequency of various types of
      platelet function disorders in Indians is similar to that in western populations
      except that the incidence of thrombopathic thrombasthenias is higher in India.

PMID- 8156037
TI  - Research in nutrition.

PMID- 8156038
TI  - The Consumer Protection Act.

PMID- 8156039
TI  - Cryptococcosis at AIIMS.

PMID- 8156040
TI  - Measures of clinical agreement.

PMID- 8156041
TI  - Surgery in patients with congenital coagulation disorders.
AB  - BACKGROUND: Surgery is occasionally necessary in patients with congenital
      coagulation disorders. Major surgery for patients with haemophilia was not being
      done in India until recently. This paper reports the experience of a single
      referral centre. METHODS: The data of 52 patients who were operated upon were
      collected from the hospital records retrospectively between 1984 and 1986 and
      prospectively thereafter. They included the surgical procedure performed,
      replacement therapy used and complications encountered. RESULTS: Fifty-nine
      procedures were performed of which 26 were major, 30 minor and 3 were diagnostic
      angiograms. Blood components produced in the hospital blood bank were commonly
      used for replacement and primary haemostasis was achieved in all patients.
      Delayed bleeding due to inadequate factor levels occurred in 12 procedures and
      was controlled by increasing the factor replacement. One patient died of
      suspected acute myocardial ischaemia. CONCLUSION: In India surgical procedures
      can be safely performed in patients with congenital coagulation disorders.

PMID- 8156042
TI  - p53 selected as molecule of the year 1993.

PMID- 8156043
TI  - Pharmacist-physician co-operation at a regional level.
AB  - In the Dutch region of "Betuwe" the hospital pharmacists and community
      pharmacists together provide short drug letters about new drugs, which are sent
      bimonthly to all the practising general practitioners (n = 83) and medical
      specialists (n = 50) in this region. A survey was conducted among these
      physicians in order to investigate their opinion about and reported use of the
      drug letters in comparison with other drug-information sources. The majority of
      the responding physicians (response rate 68%) was found to read the drug letter
      frequently and evaluated the drug letter as a useful source of information about
      drugs, especially its section about the advantages and disadvantages of the new
      drug compared to other drugs. With respect to the different stages of the drug
      adoption process, the drug letter was found to be the most frequently used
      information source at the decision stage. At the introduction stage the
      pharmaceutical industry representative seems to be the most frequently used
      source of information, while at the information stage it is the
      "Geneesmiddelenbulletin" (Drug Bulletin). The majority of the responding general
      practitioners reported to participate in local group meetings with pharmacists.
      However, in only 20% of these group meetings attention is given to the drug
      letter. Since it is known that written information has only a limited influence
      on the physician's behaviour, the influence of the "Betuwe Circulaire" may
      increase when attention is paid to it in the local contacts between pharmacists
      and physicians.

PMID- 8156044
TI  - The preservation of some oral liquid preparations. The replacement of chloroform
      by other preservatives.
AB  - Chloroform should be considered as an obsolete preservative for pharmaceutical
      preparations, because of its toxicological implications and its physical
      instability. The effectiveness of possible alternatives for chloroform in three
      oral liquid pharmaceutical preparations was investigated, using a microbiological
      challenge test. Magnesium trisilicate mixture (British Pharmacopoeia) can be
      adequately preserved with methylparaben (2 g/l). Only insignificant amounts of
      methylparaben were absorbed by the solids present in the magnesium trisilicate
      mixture. Ferrous sulfate mixture (British Pharmacopoeia) can be preserved with a
      mixture of methylparaben (1.8 g/l) and propylparaben (0.2 g/l). Sorbic acid (1
      g/l) is a suitable preservative for promethazine hydrochloride syrup.

PMID- 8156045
TI  - Can we develop improved derivatives of valproic acid?
AB  - Valproic acid is one of the major antiepileptic drugs. In animal models,
      valproate showed less anticonvulsant potency than the other three established
      antiepileptic drugs: phenobarbital, phenytoin and carbamazepine. In addition, two
      major side-effects, teratogenicity and hepatotoxicity, have been associated with
      valproate therapy. Due to the above and the shortage of new antiepileptic drugs
      there is a substantial need to develop improved derivatives of valproate. This
      paper analyses three kinds of valproate derivatives: valpromide, the primary
      amide of valproate, and its analogues; monoester prodrugs of valproate and an
      active metabolite of valproate, 2-n-propyl-2-pentenoate. The comparative
      evaluation was carried out by pharmacokinetic and pharmacodynamic analyses in
      animals. From the data accumulated so far, we can conclude that 2-n-propyl-2
      pentenoate and/or a valpromide isomer, which does not undergo amide-acid
      biotransformation and preferably is not an epoxide hydrolase inhibitor, may prove
      to be improved derivatives of the parent compound valproic acid.

PMID- 8156046
TI  - Probenecid inhibits the glucuronidation of indomethacin and O
      desmethylindomethacin in humans. A pilot experiment.
AB  - Indomethacin is metabolized in humans by O-demethylation, and by acyl
      glucuronidation to the 1-O-glucuronide. Indomethacin, its metabolite, and their
      conjugates can be measured directly by gradient high-pressure liquid
      chromatographic analysis without enzymic deglucuronidation. The pharmacokinetic
      profile of indomethacin and some preliminary pharmacokinetic parameters of
      indomethacin obtained from one human volunteer are given. In plasma only the
      parent drug indomethacin is present, while in urine the acyl and ether
      glucuronides are present in high concentrations. This confirms other reports that
      indomethacin and O-desmethylindomethacin may be glucuronidated in the kidney.
      Probenecid is a known substrate for renal glucuronidation. If indomethacin is
      glucuronidated in the human kidney like probenecid, then this glucuronidation
      might be reduced or inhibited under probenecid co-medication. This pilot
      experiment shows that probenecid reduced the acyl glucuronidation of indomethacin
      by 50% and completely inhibited the formation of O-desmethylindomethacin acyl and
      ether glucuronide.

PMID- 8156047
TI  - Epidural fentanyl and sufentanil for intra- and postoperative analgesia. A
      randomized, double-blind comparison.
AB  - In a double-blind, randomized study the efficacies of concentrated fentanyl and
      sufentanil injections as intraoperative epidural analgesics were compared. Also,
      the equivalent dose of fentanyl and sufentanil administered by continuous
      infusion during the first 24 h postoperatively, expressed in analgesia and also
      considering the side-effects was determined. 53 Patients undergoing elective
      thoracotomy, aortic surgery and bowel surgery were randomized and treated double
      blind with fentanyl 0.250 mg/ml or sufentanil 0.05 mg/ml. Preoperatively, 0.5-1
      ml study medication was administered, followed by increments of 0.2-0.5 ml during
      surgery guided by heart rate and systolic blood pressure. Postoperatively, study
      medication diluted in 1.25 mg/l bupivacaine was administered by continuous
      epidural infusion. The infusion rate was adjusted to optimize analgesia. Dose,
      heart rate and systolic blood pressure were measured intra- and postoperatively.
      Pain, sedation, nausea and pruritus were assessed on a 10 cm visual analogue
      scale. There were no differences in required volume of study medication, heart
      rate and systolic blood pressure nor in the parameters assessed postoperatively.
      Administered doses were 27.5 micrograms/h fentanyl and 5.5 micrograms/h
      sufentanil. It was concluded that 0.250 mg/ml (0.74 mumol/ml) fentanyl is
      clinically equivalent to 0.050 mg/ml (0.13 mumol/ml) sufentanil.

PMID- 8156048
TI  - Local epidermal viral infections: comparative aspects of vaccinia virus, herpes
      simplex virus and human papillomavirus in man and orf virus in sheep.

PMID- 8156049
TI  - The significance of the hydrophilic backbone and the hydrophobic fatty acid
      regions of lipid A for macrophage binding and cytokine induction.
AB  - Natural partial structures of lipopolysaccharide (LPS) as well as synthetic
      analogues and derivatives of lipid A were compared with respect to inhibit the
      binding of 125I-labelled Re-chemotype LPS to mouse macrophage-like J774.1 cells
      and to induce cytokine-release in J774.1 cells. LPS, synthetic Escherichia coli
      type lipid A (compound 506) and tetraacyl precursor Ia (compound 406) inhibited
      the binding of 125I-LPS to macrophage-like J774.1 cells and induced the release
      of tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6). Deacylated R
      chemotype LPS preparations were completely inactive in inhibiting binding and in
      inducing cytokine-release. Among tetraacyl compounds, the inhibition-capacity of
      LPS-binding was in decreasing order: PE-4 (alpha-phosphonooxyethyl analogue of
      406) > 406 >> 404 (4'-monophosphoryl partial structure of 406) > 405 (1
      monophosphoryl partial structure of 406). In the case of hexaacyl preparations,
      compounds 506, PE-1 (alpha-phosphonooxyethyl analogue of 506) and PE-2 (differing
      from PE-1 in having 14:0 at positions 2 and 3 of the reducing GlcN) inhibited LPS
      binding and induced cytokine release equally well, whereas preparation PE-3
      (differing from PE-2 in containing a beta-phosphonooxyethyl group) showed a
      substantially lower capacity in binding-inhibition and cytokine-induction. The
      conclusion is that chemical changes in the hydrophilic lipid A backbone reduce
      the capacity of lipid A to bind to cells, whereas the number of fatty acids
      determines the capacity of lipid A to activate cells. These results indicate that
      the bisphosphorylated hexosamine backbone of lipid A is essential for specific
      binding of LPS to macrophages and that the acylation pattern plays a critical
      role for LPS-promoted cell activation, i.e. cytokine induction.

PMID- 8156050
TI  - Urban outbreak of a Brucella melitensis infection in an Argentine family:
      clinical and diagnostic aspects.
AB  - An outbreak of Brucella melitensis in a family was studied. From the fourteen
      family members who ate unpasteurized goat cheese nine became ill. Patients
      included four females and five males of 8 to 75 years old. In seven of the
      patients the diagnosis was confirmed by positive blood culture for B. melitensis
      biovar 1. All the patients were analyzed by standard tube agglutination (STA) and
      standard tube agglutination with 2-mercaptoethanol (STA-2ME) tests at the time of
      diagnosis. In six of the patients, ELISA assays were used to assess the humoral
      immune anti-protein and anti-lipopolysaccharide (LPS) responses. Anti-LPS IgG
      antibodies were detected in all of the patients. Anti-proteins IgG antibodies
      were present at significant levels in all the studied patients including the STA
      2ME negative ones.

PMID- 8156051
TI  - Impairment of the human phagocyte oxidative responses caused by Leishmania
      lipophosphoglycan (LPG): in vitro studies.
AB  - Lipophosphoglycan (LPG), a surface glycoconjugate of Leishmania promastigotes,
      has been reported as playing an active role in protecting the parasite within
      phagolysosomes, by an impairment of monocyte oxidative responses. In this study
      the effect of LPG on the oxidative burst of human peripheral monocytes,
      eosinophils and neutrophils was evaluated. Our results demonstrated that either
      superoxide anion (O2-) or hydrogen peroxide (H2O2) release by LPG-pretreated
      cells was diminished, emphasizing the ability of this glycoconjugate to impair
      the oxidative activity of all phagocytes.

PMID- 8156052
TI  - In vivo human immune response to transferrin-binding protein 2 and other iron
      regulated proteins of Neisseria meningitidis.
AB  - When grown under iron restriction, Neisseria meningitidis expresses new outer
      membrane proteins, some of which are antigenic and potentially useful as vaccine
      components. This is particularly relevant to N. meningitidis serogroup B, against
      which neither polysaccharide nor conjugate vaccines are effective. We
      investigated recognition of N. meningitidis serogroup B outer-membrane antigens
      by three sera from patients recovered from meningitis. Recognition of antigens
      from the homologous strain provided information on in vivo expression during
      infection and immunogenicity, while cross-reactivity with outer membrane proteins
      from the other two strains and from another five strains in our collection
      allowed evaluation of antigenic heterogeneity. Our results demonstrate that
      transferrin-binding protein 2 (TBP2) is immunogenic in humans, to varying degrees
      depending on the strain, and that TBP2s (like the equivalent proteins of
      Haemophilus influenzae type b) are among the most important iron-regulated outer
      membrane antigens expressed during infection. Other immunogenic outer membrane
      proteins (some iron-regulated) are also expressed during infection; in a previous
      study in mouse, three of these proteins (with M(r) of 50, 70 and 77 kDa) did not
      induce an immune response. Our cross-reactivity data provide some support for
      Robki et al.'s two-group classification of N. meningitidis strains, and provide
      evidence against the possibility that the antigenic domains shared by the TBP2s
      of all N. meningitidis strains induce immune responses in vivo.

PMID- 8156053
TI  - Protective effects of orally administered, Klebsiella-containing bacterial
      lysates in mice.
AB  - The efficacy, as oral vaccines, of hepta- and mono-valent, Klebsiella-containing
      bacterial lysates and a number of control preparations was tested in mice. The
      preparations were administered during two periods of four days each, interrupted
      by an interval of 3 days. Fourteen days after the first dose, the animals were
      challenged either intraperitoneally (i.p.; peritonitis/sepsis model) or
      intranasally (i.n.; pneumonia model). Animals treated with low doses of
      Klebsiella lysate, in the form of either a 7-valent lysate or a Klebsiella
      monolysate, showed enhanced survival in both the peritonitis/sepsis and the
      pneumonia models. Hexa- and tetra-valent preparations without Klebsiella were not
      protective in the models tested. Furthermore, it was found that the protection is
      accompanied by priming for Klebsiella-specific IgG responsiveness (probably at
      the T cell level) and by significant IgA anti-Klebsiella serum antibody levels in
      about one third of the animals. The oral efficacy of Klebsiella-containing
      lysates suggests the presence of an adjacent component that directs Klebsiella
      antigen(s) to follow a selective intestinal pathway which renders them
      immunogenic. The identity of this component is under investigation.

PMID- 8156054
TI  - Intraperitoneal injection of synthetic bacterial lipopeptides does not cause a
      rise in circulating inflammatory cytokines.
AB  - The production of TNF-alpha, IL-1 and IL-6 was measured in mice after i.p.
      injections of the synthetic bacterial lipopeptide Pam3Cys-Ala-Gly, a potent
      macrophage and B cell activator in vitro. Only minor amounts of IL-6 and no TNF
      alpha were detectable in the serum of mice injected with 10 or 100 micrograms of
      Pam3Cys-Ala-Gly. Lipopeptide concentrations up to 1000 micrograms failed to
      induce IL-1, and TNF-alpha production and serum IL-6 levels were only slightly
      elevated. In contrast to Pam3Cys-Ala-Gly, i.p. injections of LPS were accompanied
      by high levels of the inflammatory cytokines TNF-alpha, IL-1 and IL-6 suggesting
      fundamental differences of the mode of action of these two substances when
      applied in vivo.

PMID- 8156055
TI  - Serological and structural features of Hafnia alvei lipopolysaccharides
      containing D-3-hydroxybutyric acid.
AB  - The serological heterogeneity of Hafnia alvei lipopolysaccharides from strains
      ATCC 13337, 1187, 1221, 114/60, 1211 and 1216, that contain D-3-hydroxybutyric
      acid, was analyzed by rocket immunoelectrophoresis, immunoblotting and passive
      hemagglutination. The significance of D-3-hydroxybutyric acid component for their
      cross-reactivity has been discussed. The results obtained allowed us to place
      four H. alvei strains (ATCC 13337, 1187, 1221 and 114/60) in one serotype (A) and
      to consider two other strains (1211 and 1216) as separate serotypes (B and C,
      respectively).

PMID- 8156056
TI  - Straight talk on the ADA.

PMID- 8156057
TI  - The warm-up procedure: to stretch or not to stretch. A brief review.
AB  - Stretching exercises are either performed alone or with other exercises as part
      of the athlete's warm-up. The warm-up is designed to increased muscle/tendon
      suppleness, stimulate blood flow to the periphery, increase body temperature, and
      enhance free, coordinated movement. The purpose of this paper is to review the
      literature regarding stretching, with the aim of defining its role during the
      warm-up. Implications of stretching on muscle/tendon flexibility, minimizing
      injury, enhancing athletic performance, and generally preparing the athlete for
      exercise are discussed. Physiology applied to stretching is also discussed
      together with different related techniques and practical aspects. A proposed
      model stretching regime is presented based on the literature reviewed.

PMID- 8156058
TI  - Comparison of two methods for calculating percent body weight on a tilt table.
AB  - Physical therapists commonly treat patients when knowledge of percent weight
      bearing is desirable during functional lower extremity exercise. The purpose of
      this study was to compare two methods for calculating percent body weight at
      different angles of inclination on a tilt table. Twenty healthy subjects were
      weighed on a spring scale in standing and on a tilt table at 5 degrees increments
      between 0 and 90 degrees of tilt. Percent body weight at each angle was compared
      to a value predicted from a trigonometric equation. Predicted values were
      significantly greater than measured values at all angles greater than 10 degrees
      of tilt. Predicted overestimation ranged from 2.8 to 14.2%. Compared to the
      trigonometric method, physical therapists can more easily and accurately
      determine percent body weight on a tilt table using a scale if total body weight
      is known. Partial weight-bearing rehabilitation could be performed on the tilt
      table by varying the degree of inclination, allowing functional lower extremity
      exercise for patients with weight-bearing restrictions. Guidelines could be
      established following a variety of injuries and orthopaedic procedures
      incorporating functional lower extremity exercises at varying percentages of body
      weight.

PMID- 8156059
TI  - Review of the afferent neural system of the knee and its contribution to motor
      learning.
AB  - Understanding the afferent neural system of the knee is considered to be vital to
      rehabilitation planning. An intricate relationship exists involving the afferent
      neural receptors in the inert and contractile tissues of the knee. Traditional
      rehabilitation strategies may not exploit this extensive afferent neural system.
      Closed kinetic chain functional training (CKCFT) may provide a method for more
      effectively rehabilitating an injured or reconstructed knee. The rationale for
      CKCFT has traditionally focused on mechanical aspects. Sensorimotor integration
      through motor learning is believed to be an important component of CKCFT. The
      purposes of this review are to discuss: 1) the afferent neural system of the knee
      with emphasis on the mechanoreceptors, 2) the influence of the afferent neural
      system of the knee on motor learning, and 3) how CKCFT uses the afferent neural
      system of the knee and motor learning during knee rehabilitation. This review
      reinforces the use of CKCFT in knee rehabilitation plans.

PMID- 8156060
TI  - Reliability of assessing patellar alignment: the A angle.
AB  - Anterior knee pain syndrome is a complex problem for clinicians and patients. One
      possible etiological factor that has been identified is malalignment of the
      patella. Recently, a clinical method to assess patellar malalignment has been
      proposed--the A angle. However, no reliability of this technique was reported.
      Therefore, the purpose of this study was to determine intrarater and interrater
      reliability for the A angle. Thirty-six subjects participated in this study.
      Three raters measured each knee twice (N = 70). Interclass correlation
      coefficients (ICC) and standard error of measurements (SEM) were determined for
      the A angle and component measurements. Intrarater A-angle values ranged from
      11.8 to 23.5 degrees. Intrarater A-angle ICCs were poor (0.20-0.32, SEM = 5.30
      7.95 degrees). Interrater A-angle ICC was poor (-0.01, SEM = 7.82 degrees).
      Results indicated that the A angle as determined in this study was not
      reproducible. Therefore, further study is needed before the A angle can be used
      as a reliable assessment tool for patellar position.

PMID- 8156061
TI  - A comparison of make and break tests using a hand-held dynamometer and the Kin
      Com.
AB  - The assessment of muscle strength is a task performed frequently by physical
      therapists. The purposes of this study were to determine whether intrasession
      test-retest reliability differs between make and break tests and strength tests
      that do not require an assessor (eg., isometric Kin-Com test) and hand-held
      dynamometer (HHD) assessments. The elbow flexor strength of 32 healthy, female
      volunteers was measured under four test conditions: Kin-Com make and break, and
      HHD make and break. Two measurements were performed for each test condition by
      the same rater. The results showed: 1) measurements obtained using the HHD
      deviated from a normal distribution, 2) comparable reliability coefficients for
      the make and break tests were obtained from the Kin-Com device, 3) there was a
      higher reliability coefficient for the make test compared with the break test for
      the HHD tests, and 4) the measured forces for the break tests were higher than
      the make tests. The results support the premise that hand-held dynamometry is a
      viable alternative to more costly modes of isometric strength measurements,
      provided the assessor's strength is greater than that of the specific muscle
      group being measured.

PMID- 8156062
TI  - Comparison of DonJoy ankle ligament protector and subtalar sling ankle taping in
      restricting foot and ankle motion before and after exercise.
AB  - Clinicians often must select an appropriate prophylactic ankle support system for
      their patients from a variety of ankle orthoses and ankle taping configurations.
      The purpose of this study was to compare the effectiveness of the DonJoy Ankle
      Ligament Protector and a newly developed ankle taping procedure in restricting
      foot and ankle motion before and after exercise. Subjects were eight males and
      eight females who reported no history of ankle injury during the 6 months prior
      to testing, neurological condition, lower extremity arthritis, lower extremity
      fracture, or cardiac or balance problems. A Biodex dynamometer and computer were
      used to impose passive moments and to measure eversion and inversion prior to
      application of the ankle support systems, following application, and following 10
      minutes of figure-of-eight running and 20 unilateral toe raises. Both ankles of
      each subject were assessed for each ankle support system. Subjects also compared
      the support systems for comfort, stability, and cosmetic acceptability. Both
      ankle support systems significantly reduced eversion and inversion following
      application and following exercise compared with preapplication measurements.
      Eversion measurements increased significantly following exercise for both ankle
      support systems compared with postapplication measurements. Inversion
      displacement following application was greater for the Ankle Ligament Protector
      than the ankle taping system. The two ankle support systems did not differ
      significantly following exercise for eversion or inversion measurements. The
      results may assist clinicians in selecting either of these ankle support systems
      for use in protection against ankle sprain injury.

PMID- 8156063
TI  - Symmetry of lumbar rotation and lateral flexion range of motion and isometric
      strength in subjects with and without low back pain.
AB  - There is substantial reason to believe that asymmetry of trunk motion plays a
      significant role in the development and presentation of low back pain. However,
      there has been little review of objective measurements of low back pain and
      asymptomatic populations to support these assumptions or the related clinical
      models. In order to study asymmetry of trunk function and its relationship to the
      presence of low back pain and laterality of symptoms, 120 subjects with low back
      pain (LBP) and 168 subjects without low back pain (NLBP) were tested for rotation
      and lateral flexion, active range of motion (ROM), and isometric strength using
      the B-200 Lumbar Dynamometer. A similar pattern of asymmetry was found in both
      NLBP and LBP populations; however, the magnitude of ROM asymmetry was
      significantly greater for the LBP subjects (p < .005). There was also a positive
      relationship between ROM magnitude of asymmetry and intratest variance in LBP
      subjects that was not evident in NLBP subjects. No relationships were found
      between isometric strength measures and LBP nor between laterality of asymmetric
      function and laterality of radiating symptoms. The asymmetry observed in the LBP
      population may be an augmented expression of normal asymmetrical performance, and
      behavioral factors may play a role in this expression. These observations may
      influence our use of lumbar function asymmetry as an objective clinical sign
      relating to specific pathological processes.

PMID- 8156064
TI  - The effects of nonswimming water exercises on older adults.
AB  - Exercise in a water medium reduces weight-bearing stresses on the skeletal
      joints, which may be advantageous for older individuals needing rehabilitation.
      The purpose of this study was to determine the effects of nonswimming exercises
      on muscle endurance, % body fat, and aerobic work capacity of an older adult
      population. Twelve subjects were in an exercise group (10 females and two males),
      and eight were in a control group (five females and three males). The mean ages
      of the groups were 65 (+/- 5.29) years and 56 (+/- 6.78) years, respectively.
      Before and after 12 weeks of training, subjects were measured three times weekly
      for resting heart rate, maximum heart rate, VO2 max, body composition, and work
      capacity in water. A general linear model ANCOVA was used with age as the
      covariate. The exercise group improved significantly (p < .05) on all dependent
      variables examined except body composition after 12 weeks. However, the control
      group experienced no significant changes on any variable over this period. In the
      comparisons between groups, the exercise group significantly surpassed the
      control group on all variables except body composition, where neither group
      experienced change. Nonswimming exercises appear to be a viable and effective
      means to improve cardiorespiratory function and physical work capacity of the
      elderly.

PMID- 8156065
TI  - Changes in muscle fiber cross-sectional area and concentrations of Na,K-ATPase in
      deltoid muscle in patients with impingement syndrome of the shoulder.
AB  - Disturbances of the stabilizing musculature are an important factor in painful
      shoulders. The important changes in the rotator cuff muscles are well
      established, but less attention is put on possible disturbances of the deltoid
      muscle. This study investigated the effect of shoulder impingement on muscle
      fiber cross-sectional area and the Na,K-pump concentration of the deltoid muscle.
      The study included six patients with impingement syndrome. Biopsies were taken
      from the affected and unaffected sides. The muscle fiber cross-sectional area and
      the Na,K-ATPase concentration was measured. There were significant decreases (p <
      0.05) in cross-sectional area of type 1 and type 2 fibers of the affected deltoid
      muscle of 25 and 18%, respectively. The Na,K-pump concentration of the affected
      muscles was reduced by 26.6% (p < 0.05).

PMID- 8156066
TI  - Effect of Donjoy Ankle Ligament Protector and Aircast Sport-Stirrup orthoses on
      functional performance.
AB  - Clinicians often are faced with the task of selecting an ankle orthosis that will
      provide protection against ankle sprain injury and will not have a deleterious
      effect on functional performance. The purpose of this study was to compare the
      effects of the DonJoy Ankle Ligament Protector (ALP) and the Aircast Sport
      Stirrup (AS) on three functional performance tasks: the 40-m sprint run, the
      figure-of-eight run, and the standing vertical jump. Subjects were eight males
      and eight females who reported no history of ankle injury during the 6 months
      prior to testing; neurological condition; lower extremity surgery or pathology;
      or cardiac, pulmonary, vascular, or balance problems. Each subject performed all
      functional tasks on the first test day with both ankles unbraced and with one
      randomly selected ankle braced with one of the two orthoses. Each subject
      returned for testing on a second day and performed all tasks with both ankles
      unbranced and with the other orthosis on the previously selected ankle. Subjects
      also rated the orthoses for comfort and support. An ANOVA indicated that braced
      data were not significantly different than unbraced data and that data for the
      two orthoses did not differ significantly for any of the functional performance
      tasks. Seventy-five percent of the subjects reported the AS was more comfortable
      than the ALP, and 63% of the subjects indicated that the ALP provided more
      support than the AS. Neither orthosis had a deleterious effect on functional
      performance. The results may assist clinicians in selecting either of these
      orthoses for use in protection against ankle sprain injury.

PMID- 8156067
TI  - Outcome in the treatment of chronic overuse sports injuries: a retrospective
      study.
AB  - Overuse injuries due to repetitive motion are common in recreational and elite
      athletes. Some overuse injuries resolve quickly after activity modification, but
      others can persist, which often prompts the patient to seek medical attention.
      This study retrospectively reviewed outcome and compliance in the treatment of
      chronic overuse sports injuries. One hundred and two patients were contacted by
      telephone an average of 27 months following their initial visit for chronic
      overuse injury. A questionnaire regarding the treatment and outcome was
      completed. Of this group, 38 (37%) claimed to be completely better, 28 (28%) were
      improved, but 36 (35%) were not better or worse. Anterior knee pain had a
      significantly worse outcome than any other injury (p < 0.05). Excluding anterior
      knee pain, 71% were improved or completely better. Neither activity modification
      nor combination treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and
      physical therapy through stretching and strengthening exercises was associated
      with a better result. Noncompliance rates were 9% for NSAID therapy and 13% for
      exercise treatment. These results indicate that chronic overuse injuries are not
      always self-limiting but can result in prolonged symptoms.

PMID- 8156068
TI  - Two measurement techniques for assessing subtalar joint position: a reliability
      study.
AB  - Proper assessment of the subtalar joint is critical for foot and ankle
      evaluation. Yet, reliability of open kinetic chain goniometric measurements of
      the subtalar joint has been poor. Two alternative techniques, navicular height
      and calcaneal position with an inclinometer, have been reported in the literature
      but lack reliability assessment. The purpose of this study was to determine the
      intertester and intratester reliability of navicular height and calcaneal
      position using an inclinometer. Thirty healthy, volunteer subjects (22 females,
      age 24 +/- 3.6 years; eight males, age 25 +/- 5.1 years) participated in this
      study. Two testers performed repeated measures on both feet of each subject (N =
      60) during two testing sessions. Testers determined the 1) subtalar neutral
      position, 2) resting position, and 3) difference between these two measurements
      using an inclinometer for calcaneal position and navicular height. Intratester
      and intertester reliabilities (ICC 2, 1), standard errors of measurement, and 95%
      confidence intervals were determined. Intertester and intratester reliability for
      calcaneal position ranged from .68 to .91 for all measurements. Intertester and
      intratester reliability for navicular height ranged from .73 to .96 for all
      measurements. We conclude that these weight-bearing measurement techniques are
      reliable and acceptable for clinical and research purposes as measured. In
      addition, we hypothesize that these measurement techniques are simpler than
      previously described open kinetic chain methods.

PMID- 8156069
TI  - Influence of hip position on measurements of the straight leg raise test.
AB  - Variations of the straight leg raise (SLR) test are described clinically;
      however, no studies have examined how these variations may affect the outcome of
      this test. This study examined whether measurements of SLR are influenced by
      position of contralateral hip (flexed vs. extended), nature of the trial (active
      vs. passive), or trial repetitions (1 vs. 2). Twenty-two healthy, young subjects
      participated in this study. A 35-mm camera recorded the position of the pelvis
      and lower limb during the performance of a right SLR. Passive SLR (opposite hip
      extended vs. opposite hip flexed) and active SLR (opposite hip extended vs.
      opposite hip flexed) were performed twice, in random order. Three different
      measures of SLR were obtained while subjects performed SLR under the
      aforementioned conditions--SLR relative to horizontal, SLR relative to pelvis,
      and pelvis relative to horizontal. Differences in SLR between opposite hip flexed
      vs. extended, passive vs. active, and trials were analyzed using a multifactorial
      analysis of variance for repeated measures. Hip position affected SLR relative to
      horizontal (p < .000) and pelvis relative to horizontal (p < .000), with an
      increase in measurement occurring with the opposite hip flexed. Nature of the
      trial (active vs. passive) affected SLR to pelvis (p < .003) and pelvis to
      horizontal (p < .000) with an increase in measurement for passive SLR. A
      difference in measurements existed between trials 1 and 2 for SLR to horizontal
      (p < .005) and for SLR to pelvis (p < .005). Although conducted on healthy
      subjects, the study points out the necessity of consistency of method when
      performing and interpreting the SLR test.

PMID- 8156070
TI  - Effects of stair-stepping exercise direction and cadence on EMG activity of
      selected lower extremity muscle groups.
AB  - Step ergometry has become a popular treatment mode in cardiovascular fitness and
      knee rehabilitation programs. The following study describes the effects of
      forward stair stepping at 35 and 95 steps/minute and forward and retrograde stair
      stepping at 60 steps/minute on the mean electromyographic (EMG) activity of the
      gluteus maximus, rectus femoris, vastus medialis, semimembranosus/semitendinosus,
      and gastrocnemius muscles. Thirty-three subjects without prior lower extremity
      pathology participated in the study. Analysis of variance was used to compare
      mean EMG activity during the knee extension phase of the different stepping
      conditions. Significant differences (p < 0.05) in mean EMGs of gluteus maximus,
      rectus femoris, vastus medialis, and gastrocnemius were noted across all
      cadences. The semimembranosus/semitendinosus EMG activity displayed a single
      significant difference between the cadences of 35 and 95. The comparison between
      forward and retrograde stepping identified only one significant difference in
      mean EMG (semimembranosus/semitendinosus). The effects of cadence on EMG activity
      should be considered when developing conditioning or rehabilitation programs for
      the lower extremity. Faster cadences result in increased peak activity of shorter
      duration for the gluteus maximus, quadriceps, and gastrocnemius. There is no
      apparent difference in EMG activity of the hamstrings due to cadence. Also,
      noting the minimal activation that occurs, stair-stepping exercise would not be
      recommended for strengthening of the hamstrings musculature.

PMID- 8156071
TI  - Urodynamic parameters in patients with slight and severe genuine stress
      incontinence: is the stress profile useful?
AB  - This study evaluates the usefulness of the urethral pressure profile (UPP)
      parameters in assessing the severity of genuine stress incontinence (GSI).
      Functional length (FL), maximum urethral closure pressure (MUCP), pressure
      transmission ratio (PTR), residual area at stress (RAS), number of patients with
      incontinent spikes (IS), and distribution of IS on UPP were determined in supine
      and standing position for 54 patients (group 1) with a 1-hour pad test < 2 g and
      compared with the values of 63 patients (group 2) with a 1-hour pad test > 2 g.
      The results were similar: FL (supine: 24 mm +/- 6/26 mm +/- 7 [P:0.2]; standing:
      26 mm +/- 8/24 mm +/- 11 [P:0.5]); MUCP (supine: 51 cm H2O +/- 23/47 cm H2O +/-
      20 [P:0.3]; standing: 45 cm H2O +/- 21/38 cm H2O +/- 18 [P:0.1]); and PTR
      (supine: 83% +/- 27/84% +/- 31 [P:0.9]; standing: 81% +/- 25 and 88% +/- 27
      [P:0.3]). But the RAS was lower (supine: 502 mm2 +/- 497/246 mm2 +/- 268 [P <
      0.009]; standing: 500 mm2 +/- 534/271 mm2 +/- 306 [P < 0.05]) in group 2. If the
      percentage of patients with IS was higher (supine: 57/93% [P < 0.001]; standing:
      54/84% [P < 0.01]) in group 2, the distribution of IS over the entire FL
      demonstrated no differences between group 1 and 2. In conclusion, except for the
      RAS, standard UPP parameters cannot be considered determinant in assessing the
      severity of GSI.

PMID- 8156072
TI  - Improved method for needle electromyography of the urethral sphincter in women.
AB  - Needle electromyography (EMG) of the urethral sphincter using the periurethral
      approach is a procedure which most women find painful and their discomfort can
      restrict the usefulness of the test. A new technique has been devised using a
      transvaginal approach. The patient lies in the left lateral position and using a
      Sims speculum the posterior vaginal wall is retracted. The urethral sphincter can
      be easily seen and palpated, assisting correct electrode placement. This new
      technique is much less uncomfortable and highly satisfactory EMG recordings are
      obtained.

PMID- 8156073
TI  - Needle EMG registration of striated urethral wall and pelvic floor muscle
      activity patterns during cough, Valsalva, abdominal, hip adductor, and gluteal
      muscle contractions in nulliparous healthy females.
AB  - The aim of the present study was to describe co-activity patterns of the striated
      urethral wall muscle and the pelvic floor muscles (PFM) during contraction of
      outer pelvic muscles. Six healthy nulliparous physical education students, mean
      age 19.5 years (19-21) participated in the study. Concentric needle EMG and a
      Dantec amplifier were used for registrations. EMG activity was continuously
      recorded with the participants lying in a supine position. EMG was recorded
      during relaxation, contraction of the PFM, valsalva maneuver, coughing, hip
      adductor contraction, gluteal muscle contraction, backward tilting of the pelvis,
      and sit-ups. The procedure was performed with the needle in the striated muscle
      of the anterior wall of the urethra and then repeated with the needle set lateral
      to the urethra in the PFM. The results showed that the striated urethral wall
      muscle was contracted synergistically during PFM, hip adductor, and gluteal
      muscle contraction, but not during abdominal contraction. Both hip adduction,
      gluteal muscle, and abdominal muscle contraction gave synergistic contraction of
      the PFM. Thus the urethral wall striated muscle and the PFM react differently
      during abdominal contraction.

PMID- 8156074
TI  - One month maximal electrostimulation for genuine stress incontinence in women.
AB  - While awaiting surgery for genuine urinary stress incontinence, 51 women with
      were treated at home for 1 month with vaginal maximal electrostimulation. They
      were evaluated subjectively, urodynamically, and with two different pad tests.
      Six patients (12%) were cured and 17 (33%) were much improved, subjectively and
      objectively. Statistically significant improvement was observed for both pad
      tests. Successful treatment was significantly more likely in women with milder
      degrees of incontinence but was unrelated to age or urethral pressure. Patient
      acceptance was excellent and apart from some vaginal soreness no complications
      were seen. Sixteen patients (31%) elected not to be operated on. These 16
      patients were reevaluated after 1 year and 13 (81%) had maintained their
      improvement. Three had disimproved but were still better than before treatment; 2
      again refused surgery and 1 opted for surgery. Therefore, 15 of 51 (29%)
      operations were saved after 1 year. This conservative treatment for stress
      incontinence is safe, simple, inexpensive, and reasonably successful.

PMID- 8156075
TI  - Stimulation of DNA synthesis in rabbit bladder wall after partial outlet
      obstruction and acute overdistension.
AB  - Partial outlet obstruction of the rabbit urethrovesical junction (UVJ) has been
      used to induce pathology in the urinary bladder characteristic of obstructive
      damage observed in humans. The purpose of the experiments reported here was to
      compare the 3H-thymidine (3H-TdR) labelling of DNA in urinary bladders of male
      New Zealand White (NZW) rabbits subjected to partial outlet obstruction or
      overdistension. A total of 18 animals was used. Two normal controls, and 12
      partially obstructed animals (at 1 day [D], 3D, 5D, 7D, 14D, and 21D) were
      injected (i.v.) with 3H-TdR at a dose of 0.5 microCi/g body weight. An additional
      4 were overdistended to volumes 120% of maximum intravesical pressure,
      immediately emptied via the catheter, and injected with 3H-TdR 24 hr (1D) later.
      All animals were sacrificed up to 3.5 hr after injection of the label. DNA
      associated radioactivity reached a peak at 3D after obstruction and was reduced
      substantially by 5D, although the level of incorporation remained well above
      control levels out to 21D. Levels of 3H-TdR incorporation 1D after overdistension
      bladders were about half of that found 1D following partial obstruction. The
      distribution of 3H-TdR labelled DNA in tissues was demonstrated by
      radioautography of histologic sections. One day following obstruction, 3H-Tdr
      incorporation was localized in the urothelium. Labelling of urothelium subsequent
      to 1D was reduced but remained above control levels until 21D. Labelled smooth
      muscle nuclei were observed only in control and 3D bladders, and they were
      measured at similar frequencies. Labelling of both intrinsic connective tissue
      (ICT) (mucosal, submucosal, and mural) and extrinsic connective tissue (ECT)
      (serosal) peaked at 3D after obstruction and declined thereafter but not to
      control levels. Labelling of ECT was, of course, limited to those bladders in
      which ECT was present (i.e., 3-21D). While the distribution of labelled cells in
      radioautograms was more variable 1D after obstruction than 1D after
      overdistension, the general cellular and biochemical responses to overdistension,
      as measured by DNA synthesis, are similar to those observed after partial outlet
      obstruction. Since the first sequela of obstruction is acute distension, these
      data support the assertion that the initial overdistension of the bladder
      initiates the cellular response to obstruction.

PMID- 8156076
TI  - 3H-thymidine uptake by the rat urinary bladder after partial outflow obstruction.
AB  - Partial outflow obstruction induces marked changes in detrusor contractile
      function and morphology. One common finding in all experimental animal models of
      outflow obstruction is a significant increase in bladder mass. It is not clear
      which tissue compartments undergo hypertrophy, hyperplasia, or both. The present
      study was designed to evaluate the time-related changes in 3H-thymidine uptake
      and distribution within each tissue compartment induced by partial outflow
      obstruction using autoradiography. Partial outlet obstruction in rats induced a
      mild 2-fold increase in mass over a 14 day period. DNA synthesis increased
      significantly at 1 day following surgery, and remained increased through 7 days.
      DNA synthesis returned to control levels by 14 days. Distribution studies (using
      autoradiography) demonstrated a marked increase in the number of labelled
      urothelium cells at 1 and 3 days after obstruction. Sham surgery also initiated
      an increase in the number of labelled cells in the urothelium at 1 day. Although
      both sham and obstructive surgeries induced substantial increases in the
      labelling of cells within the connective tissue components, the magnitude of the
      increase in labelled connective tissue cells of the obstructed bladders was
      greater than that of the sham group. The number of labelled smooth muscle cells
      of the obstructed bladder increased significantly at 3, 5, and 7 days. However,
      there were no changes in smooth muscle incorporation of 3H-thymidine by the sham
      groups. In conclusion, partial outflow obstruction induced time-dependent
      increases in bladder wall proliferation. The urothelium and connective tissue
      were the compartments first affected, followed by smooth muscle.

PMID- 8156078
TI  - Regarding "Reproducibility of pressure transmission ratios in stress incontinent
      women".

PMID- 8156079
TI  - Epistaxis as a side effect of oxybutynin in children: report of two cases.

PMID- 8156077
TI  - Intracellular mechanism of penile erection in monkeys.
AB  - To elucidate the sequence of events between the release of neurotransmitters and
      cavernous smooth muscle relaxation in erection, we studied the role of the cyclic
      adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) systems.
      In a well-established simian model, the effects of specific agonists and
      antagonists of the intracellular sequence for smooth muscle relaxation and
      potassium channel openers on the intracavernous pressure were examined. Sodium
      nitroprusside (10(-3) M), a nitric oxide releaser and thus a stimulant of the
      cGMP system, caused an increase in the intracavernous pressure from 82 to 115 cm
      H2O for 7 to 19 min and penile diameter from 24.8 +/- 2.28 to 43 +/- 4.87 mm.
      When nitroprusside was injected after methylene blue (10(-3) M), a specific
      antagonist of the enzyme guanylate cyclase, intracavernous pressure rise
      decreased significantly, but cromakalin, a potassium channel opener, provoked
      excellent increases after the block. A smaller dose of sodium nitroprusside (10(
      4) M) caused an increase in intracavernous pressure from 35 to 85 cm H2O for 7 to
      11.5 min. When nitroprusside was injected after zaprinast, a phosphodiesterase
      inhibitor, the increase in pressure ranged from 80 to 116 cm H2O for 15 to 30
      min. Prostaglandin E1, an activator of the cAMP system, caused an increase in the
      intracavernous pressure of 20-80 cm H2O for 5 to 10 min, and an increase in
      penile diameter from 25 +/- 2.22 to 35 +/- 3.48 mm. The erectile response to
      PGE1, but not to cromakalin, was nearly abolished by ethylmaleimide, an adenylate
      cyclase blocker. The response to nitroprusside was significantly greater (P <
      0.05) than to PGE1. Both systems, cAMP and cGMP, may be involved in cavernous
      smooth muscle relaxation, and cGMP is probably the predominant intracellular
      second messenger in penile erection in monkeys. Stimulants of the cGMP system,
      such as nitric oxide releasers, could represent a more physiological and
      effective approach in the treatment of erectile dysfunction.

PMID- 8156080
TI  - Quantitative differences in beta/A4 protein subtypes in the parahippocampal gyrus
      and frontal cortex in Alzheimer's disease.
AB  - The density of diffuse, primitive and classic beta/A4 protein deposits was
      estimated in sulci and gyri in the frontal cortex and parahippocampal gyrus (PHG)
      in 8 cases of Alzheimer's disease. Total beta/A4 deposit density was similar in
      the frontal cortex and PHG but the ratio of primitive and classic deposits to the
      total was greater in the PHG compared with the frontal cortex. Total beta/A4
      deposit density was greater in the depths of the sulci, but the proportions of
      the various beta/A4 subtypes were similar in sulci and gyri. Hence, increased
      density of primitive and classic deposits in the PHG could reflect enhanced
      conversion of diffuse to mature deposits whereas increased density of mature
      beta/A4 subtypes in sulci versus gyri may reflect increased beta/A4 deposition in
      the sulci.

PMID- 8156081
TI  - Dementia in Parkinson's disease.
AB  - The prevalence of dementia, assessed on the basis of the Wechsler scale (WAIS),
      was determined in a group of 88 patients with idiopathic Parkinson's disease (PD)
      lasting longer than 4 years. In this group, 19 patients (22%) were diagnosed as
      demented. They were significantly older at the time of evaluation (72.9 +/- 8.1
      vs. 63.6 +/- 11.9), and also at the onset of the disease (61.1 +/- 10.6 vs. 54.4
      +/- 12.1) than nondemented patients. Their parkinsonism, as judged on the base of
      the Activity of Daily Living Scale, was more pronounced (57.4 +/- 13.7 vs. 73.3
      +/- 15.6) and they developed psychotic side-effects of L-DOPA treatment (53% vs.
      9%) more often. A weak negative correlation between age and intellectual quotient
      (IQ) was found, and a much stronger positive correlation between education and
      IQ. 25 patients of those diagnosed previously as non-demented were reassessed for
      dementia after another 5 years of disease. Only two of them were found demented.
      Both died and an immunohistochemical study of their brains was performed. In the
      2 cases we found neuropathological features of both PD (Lewy bodies) and
      Alzheimer's disease (AD)--neurofibrillary tangles (NFT) and senile plaques (SP).
      This finding may support the hypothesis that, at least in some cases, dementia in
      PD could be due to an accompanying AD.

PMID- 8156082
TI  - Neuropsychological follow-up of parkinsonian patients with and without cognitive
      impairment.
AB  - In order to evaluate possible progression in the severity of their cognitive
      impairment, 34 parkinsonians with intellectual impairment were followed
      longitudinally for 7 years. Each patient was matched for age, sex, severity and
      duration of illness, and pharmacological treatment, with a parkinsonian patient
      without cognitive impairment. Results suggest that cognitive deficits are not
      static but rather there is a progression in the severity. Furthermore, patients
      suffering from severe dementia are more likely to die during the follow-up
      period. The prognosis of Parkinson's disease seems to be changed substantially by
      the occurrence of dementia. The natural history of parkinsonian dementia does not
      seem to differ from the history of other forms of dementia with a progressively
      disabling course leading to a complete loss of autonomy.

PMID- 8156083
TI  - EEG frequency analysis in demented and nondemented parkinsonian patients.
AB  - In an attempt to evaluate EEG changes associated with dementia in Parkinson's
      disease (PD), we performed frequency analysis in three groups of 10 subjects
      each; two with PD, and one normal control group. The PD patient groups were
      matched for age, sex, severity and duration of disease, but were discordant for
      the existence of dementia. Normals were age- and sex-matched healthy volunteers.
      The relative alpha amplitude was significantly decreased in the demented PD
      patients, unrelated to motor disability. There was a nonsignificant but
      consistent trend of increased amplitude in the delta and theta range in the
      demented PD patients as compared to nondemented PD subjects and normal controls,
      as well as increased amplitude in the theta and delta range with more severe
      motor disability in the nondemented PD patients.

PMID- 8156084
TI  - Age-specific hospital incidence rates in dementia. A record linkage study of
      first-admission rates to Scottish hospitals (1968-1987).
AB  - A random sample (n = 101,104) was taken from total general hospital admissions to
      Scottish hospitals (1:25 fraction) during the period 1968-1977. Record linkage
      was used to connect general hospital and psychiatric hospital morbidity records
      (SMR 1 and SMR 4). Patients with a subsequent admission with dementia (principal
      diagnosis ICD 9,290) were identified from the general hospital sample on follow
      up. Age-specific first-admission rates for dementia were calculated for the
      hospital population considered. First-admission rates ranged from 41.9 (per
      100,000 person-years-at-risk, PYR) for male patients aged 60-64 years to 514.2 in
      the age band 80 years and over. The equivalent figures for female patients were
      40.8 (per 100,000 PYR) and 723.1. Epidemiological research has shown an
      approximate doubling of prevalence rates every 5 years after the age of 60 years,
      and the age-banded hospital admission rates in the present study are consistent
      with this underlying pattern. Expected first-admission rates in dementia were
      calculated from admission rates in dementia and community prevalence reported in
      previous studies. Expected rates were contrasted with the rates observed in the
      present study. An estimated 6-7% of prevalent dementia cases and between 11 and
      14% of 'expected dementia admissions' achieved a recorded main diagnosis of
      dementia, and proportions were stable across age bands in the case of both
      measures. The wide discrepancy between expected and observed admission rates
      suggests relative underreporting of dementia as a principal diagnosis in hospital
      statistics.

PMID- 8156085
TI  - Clinical deterioration in probable Alzheimer's disease correlates with
      progressive metabolic impairment of association areas.
AB  - Regional cerebral glucose metabolism (rCMRG1) measured by positron emission
      tomography of 18F-2-fluoro-2-deoxy-D-glucose was studied longitudinally (interval
      ranging from 6 to 27 months) in 25 patients with probable Alzheimer's disease
      (AD). A significant decline of rCMRG1 was noted in the whole brain (p = 0.02)
      which was most pronounced in the temporoparietal (p = 0.002), frontal (p = 0.01),
      superior parietal (p = 0.01) and occipital (p = 0.03) association cortex. A
      similar decline was also present in the thalamus (p = 0.04) but not in the
      primary visual and sensorimotor cortex, basal ganglia, cerebellum and brainstem.
      The changes of rCMRG1 in the temporoparietal, frontal and occipital association
      cortex were related to the change of the Mini Mental State Examination score
      (temporoparietal: r = 0.49, p = 0.01; frontal: r = 0.40, p = 0.05; occipital: r =
      0.44, p = 0.03). The rate of clinical and metabolic decline was not related to
      age at onset, sex, family history or duration of disease. The results suggest
      that clinical deterioration and metabolic impairment in probable AD are closely
      related and dependent on progression of pathological changes in cortical
      association areas.

PMID- 8156086
TI  - Dementia accompanying motor neuron disease.
AB  - This study presents a structural and clinical description of a patient with
      dementia of motor neuron disease (D-MND), and compares and contrasts the
      neuropsychological characteristics of this patient with those of a group of
      patients with Alzheimer's disease (AD) matched by severity of dementia. The D-MND
      patient as well as the AD patients performed abnormally on all tasks that
      assessed executive/frontal functions. However, the D-MND patient tended to be
      more impaired than AD patients on tasks that required high speed decisions and on
      shifting from one strategy to another. Deficits in memory, language, and lexical
      semantic abilities were also apparent in this patient. The co-occurrence of signs
      and symptoms characteristics of 'subcortical' dementia with those of 'cortical'
      dementia suggest that the executive system dysfunction may be secondary to
      subcortical pathology.

PMID- 8156087
TI  - Correlation of dementia, neuropsychological and MRI findings in multiple
      sclerosis.
AB  - Twenty patients diagnosed as having multiple sclerosis (MS) were examined by MRI
      and 9 neuropsychological scales: MMSE, BCRS, RMB, SDMT, BNT, VM, FAS, Benton and
      Hamilton. The number and distribution of the lesions, and cerebral and corpus
      callosum atrophy were evaluated by MRI. MR images were generated by a 0.5 Tesla
      instrument utilizing T1WI, PD and T2WI imaging techniques. The results reveal (1)
      that patients with MS are impaired in a broad range of cognitive functions but
      mainly memory is affected; (2) number of lesions in the corona radiata, insula
      and hippocampus is correlated with cognitive impairment, and (3) enlargement of
      the IIIrd ventricle is an indicator of memory impairment in MS patients.

PMID- 8156088
TI  - Spatial patterns of plaques and tangles in Alzheimer's disease.

PMID- 8156089
TI  - Expression of amyloid beta-protein precursor mRNAs in cultured skin fibroblasts
      taken from patients with dementia of the Alzheimer type.

PMID- 8156090
TI  - Evidence for a selective decrease in type 1 phosphatidylinositol kinase activity
      in brains of patients with Alzheimer's disease.
AB  - We have previously shown that phosphatidylinositol (PI) kinase activity is 40-50%
      lower in cytosolic fractions of neocortical regions from brains of patients with
      Alzheimer's disease (AD) in contrast to phosphatidylinositol phosphate (PIP)
      kinase activity, which was not affected. After preparing different enzyme
      fractions by solubilization, the PI kinase activity in the salt-solubilized
      protein preparation of the temporal cortex of AD brains was predominantly
      affected (70% decrease). PIP kinase activity in AD brains was not different from
      that of control brains in any of the fractions tested. PI kinase in the salt
      solubilized fractions was inhibited (-75%) by 1% Triton X-100, whereas the PI
      kinase in the detergent solubilized protein preparation was stimulated (+80%) by
      1% Triton X-100. PI kinase activity in the salt-solubilized protein preparation
      was almost unaffected by adenosine in contrast to PI kinase activity in the
      detergent solubilized protein preparation, which was strongly inhibited by
      adenosine. These results indicate that the PI kinase that is specifically
      affected in AD is the PI 3-kinase, or type 1 PI kinase, because the fraction
      which was affected most severely has (1) a cytosolic localization; (2) a high
      sensitivity to inhibition by the non-ionic detergent Triton X-100, and (3) an
      insensitivity to adenosine inhibition, which are characteristic features of type
      1 PI kinase. The relevance of our findings is that type 1 PI kinase is thought to
      be involved in the regulation of cytoskeletal turnover processes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156091
TI  - Pheochromocytoma complicating pregnancy.

PMID- 8156092
TI  - Low cord blood levels of catecholamine from a newborn of a pheochromocytoma
      patient.
AB  - Association of pheochromocytoma and pregnancy is rare and usually related to high
      maternal and fetal mortality rates. Maternal effects of the tumor have been
      studied extensively and the clinical outcome has markedly improved during the
      last decade. However, the role of excess catecholamines on fetal development has
      been discussed very little. We report here a case of pheochromocytoma during
      pregnancy. In which catecholamine levels from the cord blood were low despite
      simultaneous elevated maternal values (1.93 and 29.46 nmol/l norepinephrine,
      respectively), possibly owing to the high activity of the catecholamine
      degradative enzymes monoamine oxidase and COMT at the placental level. We suggest
      that in pregnancies complicated by pheochromocytoma, fetal well-being may be
      related mainly to good control of maternal blood pressure instead of the amount
      of catecholamines in the fetal circulation, because the placenta performs a
      protective role through an effective process of hormone inactivation.

PMID- 8156093
TI  - Plasma catecholamines after thyrotropin-releasing hormone administration in
      hypothyroid patients before and during therapy.
AB  - In order to investigate sympathoadrenal activity in hypothyroidism we studied the
      cardiovascular and catecholamine responses to thyrotropin-releasing hormone (TRH)
      infusion in nine hypothyroid patients before and during adequate therapy and in
      seven healthy subjects. We evaluated mean arterial pressure, heart rate, plasma
      epinephrine and norepinephrine levels after TRH administration (200 micrograms
      iv) in the three groups. Mean arterial pressure, heart rate and plasma
      epinephrine levels were not different in the three groups and did not change
      after TRH administration. Hypothyroid subjects showed increased plasma
      norepinephrine levels (1.48 +/- 0.15 nmol/l), which were reduced after
      euthyroidism was reached (0.84 +/- 0.11 nmol/l) (p < 0.01). An exaggerated
      response of norepinephrine to TRH was observed in hypothyroid patients before
      therapy (incremental peak (IP) = 0.59 +/- 0.13 nmol/l) but not in hypothyroid
      patients during therapy (IP = 0.19 +/- 0.02 nmol/l p < 0.02) or in the control
      group (IP = 0.15 +/- 0.04 nmol/l; p < 0.05). This study indicated that TRH
      administration is able to influence the sympathetic activity during
      hypothyroidism in humans.

PMID- 8156094
TI  - Three years of growth hormone treatment in growth hormone-deficient adults: near
      normalization of body composition and physical performance.
AB  - Growth hormone (GH) replacement therapy in several controlled short-term trials
      have shown unanimous beneficial effects on body composition and other features.
      To evaluate more long-term effects we report data from 3 years of uninterrupted
      GH therapy in 10 GH-deficient adults who had all completed a previous double
      blind placebo-controlled study and who also had been studied after 16 months of
      open GH therapy. No further increase in linear height was observed. The initial
      increase in thigh muscle volume was maintained after 3 years of GH therapy. A
      slight increase in body weight and thigh fat volume was recorded. Exercise
      capacity and isometric muscle strength were increased significantly compared to
      the initial placebo period. This was associated with stabilized levels of resting
      heart rate and blood pressure. Glycosylated hemoglobin levels were normal and did
      not change during the study. A standard oral glucose tolerance test performed at
      the end of the study revealed no evidence of glucose intolerance. No side-effects
      were reported. Compared to an age- and sex-matched group of healthy untreated
      subjects, thigh muscle volume, exercise capacity and isometric muscle strength
      had become normalized from subnormal levels after 3 years of GH therapy. We
      conclude that long-term GH replacement therapy in GH-deficient adults is
      associated with preserved beneficial effects on body composition and physical
      performance, resulting in a near normalization of several previously abnormal
      features and adding new merits to this treatment modality.

PMID- 8156095
TI  - Early postoperative evaluation in patients with Cushing's disease: usefulness of
      ovine corticotropin-releasing hormone test in the prediction of recurrence of
      disease.
AB  - In the attempt to identify parameters that might predict the risk of recurrence
      of Cushing's disease at an early stage after successful pituitary microsurgery,
      we evaluated retrospectively the usefulness of an early postoperative
      determination of morning plasma and urinary cortisol levels and of
      adrenocorticotropin (ACTH) and cortisol responses to ovine corticotropin
      releasing hormone (oCRH) stimulation in 30 patients with pituitary-driven
      Cushing's disease followed up for 9 months to 10 years after pituitary surgery.
      At an early postoperative evaluation, while off substitutive therapy, 30
      patients, out of 36 treated by pituitary microsurgery for Cushing's disease, were
      considered in remission on the basis of subnormal (21 patients), low-normal
      (eight patients) or normal (one patient) morning plasma and urinary cortisol
      levels, whereas six patients with supranormal urinary cortisol excretion were
      considered as surgical failures. The plasma ACTH response to oCRH was subnormal
      (17 patients) or normal (four patients) in 21 patients (Group 1) and supranormal
      in nine patients (Group 2). All of the six patients with persistence of Cushing's
      disease had supranormal ACTH response to oCRH. Basal and oCRH-stimulated cortisol
      levels were subnormal in 25 out of 30 patients considered in remission. During
      long-term evaluation, six patients had recurrence of Cushing's disease 9 months
      to 5 years after surgery; their early postoperative mean basal morning plasma and
      mean urinary cortisol were higher than those recorded in patients who did not
      relapse, although a wide overlap between subjects was evident. In five out of
      these six patients urinary cortisol excretion had decreased to almost
      undetectable values during low-dose dexamethasone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8156096
TI  - Thyroid and ageing.

PMID- 8156097
TI  - Thyroid hormone status and nutrient intake in the free-living elderly. Interest
      of reverse triiodothyronine assessment.
AB  - Fasting or hypercaloric diets are established methods of inducing low
      triiodothyronine (T3) levels that resemble the sick euthyroid syndrome in adults,
      but little is known on the mechanisms of this syndrome in the elderly. Decreasing
      T3 does not seem to be an unavoidable consequence of ageing, but the role of
      illness or other factors in this decline remains unclear. The aim of this work
      was to study the influence of nutritional factors on thyroid hormone levels in
      free-living elderly subjects. A 3-day dietary survey was conducted in 440
      randomized subjects aged between 65 and 96. Cholesterol, apoproteins, prealbumin,
      hemoglobin, thyrotropin-free thyroxine (FT4), FT3 and reverse T3 (rT3) were
      assayed in each subject. Only 11 subjects had low FT3 levels, and they also had
      low levels of cholesterol, prealbumin and hemoglobin and a lower Folstein score
      compared to the rest of the population. Twenty-one subjects had isolated elevated
      rT3 levels, they were older and had significantly lower energy and fat intakes
      than the rest of the population. There was a clear reduction in FT3 levels and an
      increase in rT3 levels with age, although in the normal ranges, which occurred
      despite maintenance of a high-energy intake even in the oldest group. The FT3
      level was lower in the subjects with poor health status, whereas high rT3 levels
      were associated with low energy intake in men. Stepwise regression showed that
      hemoglobin, age and prealbumin were the best predictors of FT3 levels, whereas
      age and energy intake were the main predictors of rT3 levels.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8156098
TI  - No changes of insulin sensitivity in cystic fibrosis patients with different
      degrees of glucose tolerance: an epidemiological and longitudinal study.
AB  - Plasma glucose and insulin responses to oral glucose and insulin sensitivity by
      the euglycemic hyperinsulinemic clamp technique were investigated in 30 cystic
      fibrosis patients with normal fasting blood glucose levels and normal (N = 12),
      impaired (N = 12) or diabetic (N = 6) glucose tolerance, and in 12 control
      subjects. In a subgroup of 10 cystic fibrosis patients with non-diabetic glucose
      tolerance both oral glucose tolerance test and clamp were performed again 48-52
      months later. Following oral glucose, glycemic responses were higher in cystic
      fibrosis patients than in controls, whereas insulin responses were reduced
      significantly only in the patients with diabetic glucose tolerance. Insulin
      sensitivity did not differ significantly in the patient subgroups with different
      degrees of glucose tolerance and in controls. In the 10 patients who underwent a
      4-year follow-up, insulin responses to oral glucose decreased significantly,
      whilst insulin sensitivity did not change substantially. Insulin sensitivity
      persisted unmodified even in the patients with deteriorating glucose tolerance.
      No correlation were observed between metabolic data and clinical status of
      patients. In conclusion, in cystic fibrosis subjects with fasting euglycemia and
      different degrees of glucose tolerance: (i) insulin sensitivity is not impaired;
      (ii) eventually changes of glucose tolerance over time are not associated with
      modifications of insulin sensitivity; (iii) insulin secretion deteriorates over
      time even in the patients with stable glucose tolerance; (iv) eventual
      deterioration of both glucose tolerance and insulin secretion is not linked to a
      worsening of either nutritional or clinical parameters.

PMID- 8156099
TI  - Estradiol and progesterone production by cultured granulosa cells cryopreserved
      from in vitro fertilization patients.
AB  - Gonadotropin-stimulated steroidogenesis was studied in cultured human granulosa
      lutein cells obtained from patients undergoing procedures for in vitro
      fertilization. The impact of cryopreservation on cell function in vitro was
      studied. Granulosa cells obtained from in vitro fertilization patients were
      cultured in serum-supplemented medium or cryopreserved at -135 degrees C for 2-22
      months. Fresh (unfrozen) cells (10(5) produced estradiol at a rate of 1320 pmol/l
      (over 72 h) and progesterone at about 2500 nmol/l. Estradiol production by either
      fresh or cryopreserved granulosa cells in culture was unaffected by physiological
      concentrations of follicle-stimulating hormone (7 IU/l). Adding testosterone (10(
      7) mol/l) to the medium increased estradiol secretion approximately sixfold. In
      contrast, progesterone production was not affected by follicle-stimulating
      hormone or testosterone. No significant differences were observed in cultures of
      cryopreserved granulosa cells compared to cultures of unfrozen cells with respect
      to estradiol secretion, the effects of follicle-stimulating hormone or
      testosterone on estradiol secretion, or progesterone production. Progesterone
      production by fresh and cryopreserved cells was stimulated by human chorionic
      gonadotropin. These data indicate that cryopreservation offers the potential to
      facilitate prospective studies utilizing large numbers of human granulosa-lutein
      cells in culture.

PMID- 8156100
TI  - Identification and characterization of insulin-like growth factor I (IGF-I) and
      IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in bovine adrenal cells.
AB  - We have identified and characterized insulin-like growth factor I (IGF-I) and IGF
      II/mannose-6-phosphate (IGF-II/M6P) receptors in bovine adrenal cells. Iodine-125
      labeled IGF-I ([125I]IGF-I) binding was characteristic of the IGF-I receptor, and
      binding kinetics as well as receptor densities were similar in cortical and
      medullary membranes. Scatchard analysis of [125I]IGF-I binding to cultured
      adrenocortical cells showed a single class of high-affinity binding sites with a
      Kd of 1.4 nmol/l and an average of 150,000 binding sites/cell. Affinity cross
      linking experiments displayed a band at an apparent molecular weight of 135 kD,
      corresponding to the size of the alpha-subunit of the IGF-I receptor. In analogy,
      the binding of [125I]IGF-II to bovine adrenal membranes was characteristic of the
      IGF-II/M6P receptor and no differences between cortical and medullary membrane
      fractions were found. Scatchard analysis revealed a single class of high-affinity
      binding sites in adrenocortical cells with a Kd of 1.1 nmol/l and an average of
      280,000 binding sites/cell. The identity of the IGF-II/M6P receptor was confirmed
      by western blotting of adrenocortical membranes with an anti-IGF-II/M6P receptor
      antibody and by affinity cross-linking of adrenocortical cells with labeled IGF
      II. In conclusion, we have identified and characterized IGF-I and IGF-II/M6P
      receptors in bovine adrenocortical as well as medullary cells. In both regions of
      the bovine adrenal gland the IGF-II/M6P receptor is much more abundant than the
      IGF-I receptor.

PMID- 8156101
TI  - Stimulation of endothelin-1 production by thrombin, but lack of interference by
      high ambient glucose in vitro.
AB  - Diabetic vascular disease is associated with a state of hypercoagulability and
      altered endothelial properties, leading to elevated plasma levels of endothelium
      derived peptides and proteins, e.g. endothelin-1, von Willebrand factor or
      fibronectin. This study determined dynamic immunoreactive endothelin-1 secretion
      by human umbilical vein endothelial cells exposed to thrombin (5 x 10(6) mU/l) in
      the presence (40 mmol/l) and absence (5.5 mmol/l) of excessive glucose in the
      cell culture medium. Exposure to high glucose and thrombin concentrations was
      initiated after cell confluency and applied for 24 h for measurements of
      endothelin-1 and for 2 and 5 h for the determination of preproendothelin-1, von
      Willebrand factor and fibronectin messenger ribonucleic acid. Comparisons were
      made versus cells incubated with normal glucose concentrations or with high
      mannose or NaCl concentrations as osmotic control. Neither preproendothelin-1,
      fibronectin and von Willebrand factor messenger ribonucleic acid expression nor
      endothelin-1 release was affected by high concentrations of glucose, mannose or
      sodium chloride.

PMID- 8156102
TI  - Increased ratio between anaerobic and aerobic metabolism in lymphocytes from
      hyperthyroid patients.
AB  - While an increased oxygen consumption is accepted as one consequence of
      hyperthyroidism, only few data are available on the role of anaerobic processes
      for the increased metabolic activity in this disease. In this study we evaluated
      the relative importance of anaerobic and aerobic metabolism for the metabolic
      activity in lymphocytes from patients before and after treatment for
      hyperthyroidism. Total lymphocyte heat production rate (P), reflecting total cell
      metabolic activity, was determined in a plasma lymphocyte suspension using direct
      microcalorimetry. The contribution from aerobic metabolism (O2-P) was calculated
      from the product of the lymphocyte oxygen consumption rate and the enthalpy
      change for glucose combustion, and the anaerobic contribution as the difference
      between P and O2-P. The total lymphocyte heat production rate P was 3.37 +/- 0.25
      (SEM) pW/cell (N = 11) before and 2.50 +/- 0.11 pW/cell (N = 10) after treatment
      for hyperthyroidism (p < 0.01) as compared to 2.32 +/- 0.10 pW/cell in a control
      group (N = 18). The aerobic component O2-P amounted to 1.83 +/- 0.11 pW/cell in
      the patient group before and 1.83 +/- 0.08 pW/cell after treatment and to 1.71 +/
      0.16 pW/cell in 10 controls. Out of P, the O2-P component corresponded to 56.8
      +/- 4.4% in the hyperthyroid state and to 73.7 +/- 3.2% after treatment (p <
      0.01) as compared to 73.4 +/- 4.4% in the 10 euthyroid controls. It was concluded
      that the increased metabolic activity demonstrated in lymphocytes from
      hyperthyroid patients cannot be explained by an increased oxygen-dependent
      consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156103
TI  - Cardiac triiodothyronine nuclear receptor binding capacities in amiodarone
      treated, hypo- and hyperthyroid rats.
AB  - Parameters that are assumed to be under direct control by thyroid hormonal state
      were evaluated in amiodarone-treated, hypo- and hyperthyroid rats. Special
      attention was paid to evaluating similarities between hypothyroid and amiodarone
      treated rats, with special focus on myocardial nuclear triiodothyronine (T3)
      receptor binding characteristics. Rats were rendered hypothyroid by adding KClO4
      to the drinking water for 6 weeks (N = 14). Hyperthyroidism was induced by adding
      0.003% L-thyroxine to the drinking water for 6 weeks (N = 14). Fourteen rats were
      treated orally for 6 weeks with amiodarone, whereas 14 rats served as untreated
      controls. Equilibrium binding characteristics for T3 nuclear receptors were
      determined by means of a simple and rapid method with excellent reproducibility
      and sensitivity. Body temperature and heart rate were lowered in hypothyroid and
      amiodarone-treated rats. Maximum binding capacities of beta-adrenergic receptors
      were reduced by 39% and 14% (p < 0.05) in hypothyroid and amiodarone-treated
      rats, respectively, and increased by 28% (p < 0.05) in hyperthyroid rats. Maximum
      binding capacities for voltage-operated Ca2+ channels were increased by 35% and
      16% in hypothyroid and amiodarone-treated rats (p < 0.05), respectively, and
      decreased by 24% in hyperthyroid rats (p < 0.05). Maximum binding capacities for
      T3 receptors (expressed per unit of DNA) were reduced by 39% and 32% in
      hypothyroid and amiodarone-treated rats (p < 0.05), respectively, and increased
      by 63% in hyperthyroid rats (p < 0.05). In hypothyroid and amiodarone-treated
      rats, myocardial T3 content was extremely reduced (less than 0.05 nmol/kg and
      0.06 +/- 0.08 nmol/kg, respectively, compared with control levels of 1.55 +/-
      0.46 nmol/kg). In vitro competition studies of amiodarone and its desethyl
      analogue revealed that both drugs are potentially capable of displacing T3 from
      its nuclear receptor at concentrations close to what are considered therapeutic
      drug levels. Myocardial nuclear T3 receptor maximum binding capacities decreased
      to a similar degree in hypothyroid and amiodarone-treated rats and increased in
      hyperthyroid rats. Several other similarities between hypothyroid and amiodarone
      treated rats suggest that amiodarone may act by inducing a state of thyroid
      hormonal resistance.

PMID- 8156104
TI  - Centrally administered vasopressin modifies stress hormone (cortisol, prolactin)
      secretion in sheep under basal conditions, during restraint and following
      intravenous corticotrophin-releasing hormone.
AB  - The effects of central (lateral ventricle) injections of vasopressin (2.5, 25 or
      250 ng) on cortisol and prolactin release were investigated in castrated male
      sheep (N = 6) under basal (non-stress) conditions, during 120min of physical
      restraint and following peripheral injection of ovine corticotrophin-releasing
      hormone (oCRH). Cortisol and prolactin concentrations in non-stressed sheep were
      raised significantly (p < 0.05) in the 120 min following administration of 250 ng
      of vasopressin. The prolactin response to restraint stress was decreased (p <
      0.05) in the 30-min period following central injection of 250 ng of vasopressin.
      The stimulatory effect of oCRH on cortisol release was enhanced (p < 0.05) by
      vasopressin (25 and 250 ng), whereas prolactin levels decreased (p < 0.02) in the
      30-min period following injection of the highest dose of vasopressin. None of the
      central doses of vasopressin significantly altered plasma levels of this hormone,
      although vasopressin secretion was increased during restraint.

PMID- 8156105
TI  - Involvement of autocrine mechanism of transforming growth factor-beta in the
      functional differentiation of pregnant mouse mammary gland.
AB  - We studied the presence and possible role of the autocrine mechanism of
      transforming growth factor-beta (TGF-beta) in pregnant mouse mammary gland.
      Northern blot analysis revealed the expression of the TGF-beta 1 gene transcript
      at 2.5 kb in mammary epithelial cells isolated from virgin and mid-pregnant mice.
      The TGF-beta activity was higher in the conditioned medium from mid-pregnant
      mouse mammary explants than that from virgin explants by a bioassay system using
      mink lung epithelial cells. A binding study using [125I]TGF-beta 1 as a ligand
      showed that pregnant mouse mammary epithelial cells possessed a single class of
      high-affinity TGF-beta 1 binding sites (Kd = 28.0 pmol/l, 1.2 x 10(4) sites per
      cell). These results suggested the presence of a TGF-beta autocrine mechanism in
      pregnant mouse mammary epithelial cells. Next, we examined the effect of TGF-beta
      1 on the functional differentiation of pregnant mouse mammary gland. Transforming
      growth factor-beta 1 inhibited alpha-lactalbumin production in cultured mammary
      explants from mid-pregnant mice in a dose-dependent manner without inhibiting DNA
      synthesis. All these results suggest that TGF-beta may play a role in regulating
      the functional differentiation of mouse mammary glands during pregnancy.

PMID- 8156106
TI  - Effect of thyroid status on the oxidative capacity of Sertoli cells isolated from
      immature rat testis.
AB  - Our previous studies indicate the Sertoli cell as a target for thyroid hormone
      action at testis level. In the present study we evaluated the effect of thyroid
      hormone on Sertoli cell oxidative capacity measured by specific cytochrome
      oxidase (COX) activity and intracellular adenosine triphosphate (ATP) content.
      Sertoli cells were isolated from 21-day-old rats. Hypothyroidism, induced from
      the day of birth by administration of 0.025% methimazole, was characterized by a
      severe delay of body and testis growth and resulted in a lower COX activity (
      40%, p < or = 0.01) and a lower ATP content (-35%, p < or = 0.01) by isolated
      Sertoli cells. Administration of triiodothyronine (10 micrograms/100 g body wt on
      alternate days) to hypothyroid rats improved body and testis growth and restored
      both COX activity and ATP content. The presence of high-affinity, low-capacity
      binding sites for triiodothyronine in Sertoli cell mitochondria also was
      demonstrated. This study, unlike that carried out on the whole testis from adult
      rats, demonstrates that thyroid hormone affects the energy metabolism of Sertoli
      cells from midpubertal rat testes.

PMID- 8156107
TI  - Effects of rat corticotrophin-releasing factor, arginine vasopressin and oxytocin
      on the secretions of adrenocorticotrophic hormone and corticosterone in the fetal
      rat in late gestation: in vivo and in vitro studies.
AB  - The effects of rat corticotrophin-releasing factor (rCRF), arginine vasopressin
      (AVP) and oxytocin (OT) were investigated in vivo in 21-day-old rat fetuses
      injected through the umbilical vein and in vitro on perifused anterior pituitary
      glands from 21-day-old rat fetuses. In vivo, rCRF (1.25 pmol.50 microliter
      1.fetus-1), AVP (5 pmol.50 microliter-1.fetus-1) alone and rCRF in association
      with AVP or oxytocin (12.5 pmol.50 microliter-1.fetus-1) increased plasma
      adrenocorticotrophic hormone (ACTH) and corticosterone levels only 30 min after
      the start of injection. During the first 10 min of the sampling period, the
      injection of these peptides alone or in combination and the injection of saline
      decreased the plasma ACTH concentration, which was lower than that of uninjected
      fetuses, but had no effect on the plasma corticosterone concentration. In vitro,
      the release of ACTH by perifused anterior pituitary glands was increased strongly
      by rCRF (4 pmol/0.5 ml) but only slightly by AVP (92 pmol/0.5 ml) and oxytocin
      (198 pmol/0.5 ml). Arginine vasopressin and oxytoxin potentiated the release of
      ACTH stimulated by rCRF in vitro but not in vivo. Our results suggest that rCRF
      is the major peptide that controls ACTH secretion in the fetal rat at term. In
      conclusion, the rise of the ACTH level observed only 30 min after injection of
      rCRF or AVP suggests the existence of a factor able to inhibit the ACTH response
      after injection of these peptides. This factor might be elicited by the blood
      volume expansion.

PMID- 8156108
TI  - Cortisol decreases 2[125I]iodomelatonin binding sites in the duck thymus.
AB  - The immunosuppressive effect of chronic glucocorticoid treatment on
      2[125I]iodomelatonin binding in the duck thymus was studied. Two-week-old ducks
      were injected intraperitoneally with either 1 mg of cortisol per day
      (experimental group) or an equivalent volume of vehicle (control group) in the
      middle of the light period for 7 days. 2[125I]Iodomelatonin binding assays were
      performed on thymic membranes. Cortisol injection reduced the body weight gain,
      size of the bursa of Fabricius and absolute weights of the primary lymphoid
      organs but had no effect on the spleen weights. The relative weights of the
      spleen were increased while those of the primary lymphoid organs were unchanged.
      The density of the thymus 2[125I]iodomelatonin binding sites was decreased while
      the affinity was not affected. The modulation of the thymic 2[125I]iodomelatonin
      binding sites by changes in the immune status of the duck suggests that these
      binding sites represent physiologically relevant melatonin receptors and that
      melatonin exerts its action on the lymphoid tissues directly. Our findings
      support the hypothesis that the thymus is the target site for the
      immunomodulatory interactions between the pineal melatonin and the adrenal
      steroids. A possible inhibitory influence of adrenal steroids on the immuno
      enhancing effect of melatonin is also suggested.

PMID- 8156109
TI  - Assessment of alkaline reflux in children after Nissen fundoplication and
      pyloroplasty.
AB  - During an eight month period, 22 children less than 15 years of age (mean age of
      three years and seven months) who underwent operative treatment of
      gastroesophageal reflux (GER) were selected for study. All were symptomatic and
      unresponsive to medical therapy. Preoperative evaluation included esophageal pH
      probe monitoring in 18 patients, gastric isotope emptying study in 18 patients
      and contrast studies of the upper part of the gastrointestinal tract in ten
      patients. Four children with severe neurologic disorders who required placement
      of a feeding gastrostomy tube underwent fundoplication without preoperative
      evaluation. All 22 patients had GER and 14 had documented delayed gastric
      emptying (greater than 60 percent residual at 90 minutes) on radionuclide scan
      with appropriate meal for age. Each child underwent Nissen fundoplication and
      tube gastrostomy. Sixteen patients also had a modified pyloroplasty with a 2.5 to
      4.0 centimeter vertical seromuscular incision on the antrum. When the patients
      achieved a full feeding schedule (postoperative day range three to 21 days, mean
      of 6.2 days), they were put on a fast for six hours and an aspirate was obtained
      from the gastrostomy tube. Analysis of pH and bile acid content served as
      indicators of alkaline reflux. The six children without pyloroplasty served as
      the control group. Intragastric pH ranged from 1.91 to 7.00 (mean of 3.71) and
      bile acid content ranged from 4 to 150 micrometers per liter (mean of 62
      micrometers per liter). No significant differences were seen between patients
      with fundoplication alone and those with fundoplication and pyloroplasty (p =
      0.97 for pH; p = 0.66 for bile acid content). Two patients with pyloroplasty
      showed slight elevation of intragastric bile acid content at the upper limits of
      normal. At follow-up evaluation from nine to 23 months (mean of 18 months), all
      patients were asymptomatic, with only two showing rare gagging. Additionally,
      nine patients have had complete resolution of their pulmonary symptoms. No
      patients demonstrated diarrhea, gas bloat or dumping. Nissen fundoplication
      combined with a modified pyloroplasty or "antroplasty" for delayed gastric
      emptying provides excellent clinical results with minimal demonstrable bile acid
      reflux and no change in intragastric pH at the one and one-half year follow-up
      evaluation.

PMID- 8156110
TI  - Oral calcium supplements to enhance early hospital discharge after bilateral
      surgical treatment of the thyroid gland or exploration of the parathyroid glands.
AB  - One hundred and seventy consecutive patients undergoing parathyroid gland
      exploration and bilateral thyroidectomy received, postoperatively, routine oral
      calcium supplementation, close monitoring of total serum calcium, and addition of
      vitamin D for specific criteria, all to accomplish a postoperative course free of
      symptomatic hypocalcemia and early discharge from the hospital. Twelve of these
      patients underwent simultaneous thyroid gland and parathyroid gland operation.
      Parathyroid gland manipulation during these operations was aggressive. Of the 58
      patients undergoing parathyroid exploration, two required hospitalization for
      more than three days to treat hypocalcemia. No patients required intravenous
      calcium and 17 of the last 24 having total serum calcium greater than or equal to
      9.0 milligrams per deciliter at 36 hours were discharged uneventfully on the
      morning of the second postoperative day. Of the 124 patients undergoing bilateral
      thyroidectomy, four required hospitalization in excess of three days for
      hypocalcemia, one required intravenous calcium and one still requires daily
      vitamin D after a year. Eighty-five of the last 96 patients having a total serum
      calcium greater than or equal to 8.5 milligrams per deciliter at 36 hours were
      discharged on the morning of the second postoperative day, without subsequent
      hypocalcemic events. These data suggest that a program of calcium supplementation
      combined with enthusiastic outpatient support can be the future basis for same
      day or one day admissions after parathyroid gland or extensive thyroid gland
      operations.

PMID- 8156111
TI  - Stereotactic aspiration biopsy of nonpalpable nodules of the breast.
AB  - To evaluate the reliability of stereotactic aspiration biopsy (SAB) in assessing
      which nonpalpable nodules of the breast should be excised, SAB was performed upon
      373 nodules. The nodules were classified as well-circumscribed or irregular and
      evaluated for the presence of microcalcifications. The cytologic diagnoses were
      classified as malignant, atypical or benign. Cytologically malignant and atypical
      nodules were excised. Benign nodules were excised if there was a family or past
      history of carcinoma of the breast or if they changed mammographically. Twenty
      five nodules proved to be malignant. Of these, the diagnoses by stereotactic
      aspiration biopsy were adenocarcinoma in 20 patients, atypical in three,
      malignant hemangiopericytoma in one patient and benign in one. The borders of the
      malignant nodules were well-defined in eight patients and irregular in 17. Three
      malignant nodules with irregular borders had clustered microcalcifications. One
      false-positive instance was a sclerosing papilloma with atypical hyperplasia.
      Twenty-four nodules with benign cytologic diagnoses, which were excised, proved
      to be benign. An additional 132 nodules with benign cytologic diagnoses had six
      month interval mammograms for two years; 131 were without interval change and one
      increased in size and proved to be a carcinoma. SAB is reliable for diagnosing
      nonpalpable nodules. Nodules with malignant and atypical results must be excised.
      It is reasonable to have follow-up evaluation of well-defined nodules
      mammographically when the aspirate is benign.

PMID- 8156112
TI  - Composite dialysis access grafts.
AB  - Hemodialysis access devices constructed of expanded polytetrafluoroethylene
      (ePTFE) require a maturation period of seven to 14 days before cannulation.
      Percutaneously placed dual-lumen catheters can be used for temporary access
      during this interval but are associated with significant short and long term
      complications. Access devices constructed of Plasma-TFE (pl-TFE) (Atrium, Hollis)
      conduits have been reported to tolerate cannulation immediately after placement,
      but long term patency is inferior to that of conventional ePTFE. To combine the
      immediate access advantages of pl-TFE and the long term patency of ePTFE,
      composite grafts were constructed, which consisted of 10 to 12 centimeters of pl
      TFE and the remainder of ePTFE. The pl-TFE segment was made available for
      immediate access and the ePTFE segment after an appropriate maturation period.
      Thirty percent of composite grafts were cannulated on the day of placement and
      83.8 percent were cannulated within 72 hours. No complications of early access of
      the pl-TFE segment occurred. These grafts were compared with a cohort of
      conventional ePTFE grafts for the occurrence of thrombosis, infection and
      pseudoaneurysm. No significant differences were noted. Event-free patency of the
      two groups was equal (327.7 versus 346.3 days, p = 0.282). Patency after an
      initial thrombotic episode was slightly better in the composite group. We
      conclude that composite dialysis access grafts can be cannulated immediately
      after placement and demonstrate long term performance at least equal to that of
      conventional ePTFE grafts. Use of the composite graft concept should be
      considered when immediate dialysis is needed and to avoid the use of temporary
      access catheters.

PMID- 8156113
TI  - Lactiferous fistula.
AB  - Lactiferous fistula, or Zuska's disease, is a rare recurrent condition
      characterized by draining abscesses about the nipple on one or both breasts.
      Because little is known about the disease, it is often misdiagnosed and
      inappropriately treated. We reviewed the medical records of 51 women diagnosed as
      having lactiferous fistula at The Cleveland Clinic Foundation between 1961 and
      1991. The clinical features were tabulated. An experienced breast pathologist
      reviewed the specimens of all the patients, and surgical techniques were
      compared. Patients ranged in age from 14 to 66 years, with a mean age of 40
      years. Thirty-six patients had a swelling or mass at the areola, 51 had a
      draining fistula from the subareolar tissue, 40 had a chronic thick, pasty
      discharge from the nipple and 35 reported pain with the discharge. Fourteen
      patients had unsuccessful operations elsewhere, including four women who had
      subcutaneous mastectomies before coming to us. The average duration of symptoms
      was 3.2 years and the average follow-up period postoperatively was 51 months. On
      histologic examination, we found that, in all instances, keratinizing squamous
      epithelium had replaced the lining of one or more lactiferous ducts for a
      variable distance into the subareolar tissue. Core excision of the fistula and
      all of the retroareolar fibroglandular tissue and the ductal tissue within the
      nipple proved to be the definitive therapy in 47 of the 48 patients who had
      follow-up evaluation.

PMID- 8156114
TI  - Ultrasound guided biopsy of nonpalpable and difficult to palpate thyroid masses.
AB  - We reviewed our experience with ultrasound-guided biopsies of masses of the
      thyroid gland that were either nonpalpable or difficult to localize by palpation
      to evaluate the technique and correlate the results. Thirty-two biopsies were
      performed upon 25 patients whose clinical presentations were palpable nodule (six
      patients), throat discomfort (two patients), postpartial thyroidectomy follow-up
      evaluation (two patients), incidental discovery of a mass--by ultrasound of the
      neck (two patients), roentgenogram of the chest (two patients), computed
      tomography of the chest (one patient) and during tracheostomy placement (one
      patient). Other presentations were eliminate infection (one patient), odynophagia
      (one patient), hoarseness (one patient), cold nodule on a nuclear medicine study
      (one patient), hyperparathyroidism (one patient), rule out metastasis from
      carcinoma of the colon (one patient), persistent cough (one patient), enlarged
      thyroid gland (one patient) or family history of carcinoma of the thyroid gland
      (one patient). Fifteen patients had nuclear medicine studies showing either a
      cold nodule (ten patients), multinodular goiter (one patient), normal examination
      (two patients), hot nodule (one patient) or no thyroid gland activity (one
      patient). The ultrasound examinations showed either a hypoechoic nodule (25
      patients), inhomogeneous or mixed echogenic nodule (six patients) or a
      hyperechoic nodule with hypoechoic rim (one patient). The nodules ranged in size
      from 3 milliliters to 7 centimeters. Twenty-six lesions were less than 3
      centimeters in diameter; of the other six, four were substernal goiters. Six
      patients had a previous nondiagnostic biopsy directed by palpation only. Biopsy
      was performed using real-time ultrasound guidance with various needles. One
      patient had a small hematoma, which was the only complication in the study. The
      results of the biopsies were diagnostic in 26 of 32 patients. The final diagnosis
      was benign follicular cells (ten patients), adenomatous nodule (seven patients),
      follicular neoplasm (three patients), colloid cyst (two patients), aspergillus
      (two patients), fibrosis (one patient) and papillary carcinoma (one patient). Six
      of the biopsies yielded unsatisfactory specimens. One of the patients with a
      diagnosis of benign follicular cells on biopsy had a follicular carcinoma after
      surgical pathologic factors were obtained; that was the only false-negative
      result. We conclude that ultrasound-guided biopsy of the thyroid is a safe and
      useful method of evaluating nonpalpable and difficult to palpate thyroid masses.

PMID- 8156115
TI  - Lymph node staging in 872 patients with carcinoma of the stomach and the presumed
      benefit of lymphadenectomy. German Stomach Cancer TNM Study Group.
AB  - The incidence of surgically suspected and microscopically proved lymph nodes from
      adenocarcinoma of the stomach and the results of systematic lymphadenectomy have
      been studied and correlated to survival rate of 99.4 percent at a follow-up
      period of five years in 872 patients who underwent resection as a part of a
      prospective observational study in carcinoma of the proximal and distal parts of
      the stomach. Surgeons believe that, in the median, only one-fifth of the patients
      with and without systematic lymphadenectomy had positive nodes, whereas
      pathologists found almost three-fourths of positive lymph nodes (72.7 percent) in
      patients with proximal carcinoma of the stomach as compared with those without
      systematic lymphadenectomy (30.8 percent). The figures for middle and lower third
      carcinomas were even higher (63.5 versus 13.9 percent and 75.9 versus 27.1
      percent). Positive nodes were most common in the perigastric area and their
      distribution was clearly related to the site of the tumor. Frequently, however,
      lymph node groups were involved, far from the primary, that is, along the
      hepatoduodenal ligament in 9 to 19 percent of patients with carcinoma of the
      proximal part of the stomach and in 7 to 16 percent of patients with carcinoma of
      the distal part of the stomach. There were some hints of a better survival rate
      for patients with systematic lymphadenectomy as compared with those without, only
      for low stage carcinoma of the stomach (TNM stage IA-IB, p = 0.1157, Breslow). We
      suggest a more extensive operation with gastric resection, always combined with
      systematic lymphadenectomy if no distant metastases are found.

PMID- 8156116
TI  - Flap reconstruction of the stenotic vagina.
AB  - Reconstruction of the congenital or acquired stenotic vagina has traditionally
      been accomplished by skin grafting or reverse perineorrhaphy in addition to other
      less successful methods. The advent of musculocutaneous flaps has provided an
      excellent means of reconstructing the vagina after exenterative surgical
      treatment; however, the bulk associated with these flaps has precluded their use
      in reconstruction of the stenotic vagina. Thin, supple, axial pattern
      fasciocutaneous flaps based on the terminal branches of the internal pudendal
      artery provide a reliable and durable vaginal lining after surgical enlargement.
      Seven flaps have been used in four patients without complications. A follow-up
      period of greater than three years has yielded excellent results.

PMID- 8156117
TI  - Treatment of giant hemangiomas of the liver by enucleation.
AB  - Cavernous hemangiomas are the most common benign tumors of the liver. The results
      of natural history studies have demonstrated that asymptomatic hemangiomas can be
      observed without deleterious results. The appropriate treatment for symptomatic
      cavernous hemangiomas remains unclear. Since 1987, ten patients with symptomatic
      giant cavernous hemangiomas have undergone simple enucleation at the New England
      Deaconess Hospital, Boston, Massachusetts. Ten patients who underwent both
      anatomic and nonanatomic resections for benign hepatic tumors were chosen as a
      control group. We analyzed patient demographics and characteristics of the
      hospital course. Both groups had similar periods of hospitalization (9.5 +/- 1.2
      versus 9.1 +/- 1.8 days; p = NS), operative time (2.2 +/- 0.3 versus 2.4 +/- 0.2
      hours; p = NS) and lesion size (7.6 +/- 1.3 versus 8.4 +/- 1.2 centimeters; p =
      NS). The enucleation group had 49 percent less intraoperative blood loss when
      compared with the resection group (400 +/- 129 versus 742 +/- 116 milliliters; p
      < 0.05). Two units of blood were transfused in the enucleation group while 6
      units were transfused in the resection group. Postoperatively, two patients in
      the resection group required computed tomographic guided drainage of extrahepatic
      bile collections. There were none in the enucleation group. Because enucleation
      is performed in the fibrous capsule composed of compressed hepatic parenchyma,
      injury to major bile ducts and blood vessels may be avoided. Enucleation is a
      safe alternative to resection for treatment of symptomatic giant hemangiomas.

PMID- 8156118
TI  - Stereotactic fine needle aspiration of mammographic lesions.
AB  - Stereotactic fine needle aspiration biopsy (FNAB) is being offered at many
      centers across the United States in lieu of open surgical biopsy for nonpalpable
      mammographic lesions. To determine how accurate this procedure is in a community
      hospital, the authors performed stereotactic FNAB of 62 nonpalpable mammographic
      lesions using Siemens upright stereotactic equipment. FNAB was immediately
      followed by hook wire localization and open biopsy. Ten lesions were
      histologically malignant. Seven of these had been identified cytologically as
      atypical, suspicious or malignant. Three carcinomas were undetected by FNAB, for
      a sensitivity rate of 70 percent. There were no false-positive FNAB diagnoses.
      Three different radiologists performed the FNAB and localizations. Our results
      were insufficiently sensitive to be able to offer stereotactic FNAB to patients
      in lieu of open surgical biopsy. We are currently planning to evaluate the
      dedicated stereotactic prone biopsy equipment to compare the results of needle
      core biopsies with subsequent hook wire localization and open biopsy.

PMID- 8156119
TI  - New patterns of transplant nephrectomy in the cyclosporine era.
AB  - Several significant advances in transplantation during the last decade, among
      them the introduction of cyclosporine, have greatly altered the management of
      allograft recipients. To determine the frequency and pattern of transplant
      nephrectomy (TN) since cyclosporine was introduced in 1984, we reviewed our
      results from 1968 through 1990. During the 23 year period, 766 renal transplants
      were performed; 280 before 1984, when cyclosporine was first introduced into
      routine care and 486 after that time. Of the 280 recipients undergoing
      transplantation before 1984, 70 underwent TN, whereas only 61 of the 486
      recipients in the cyclosporine period have undergone TN (p < 0.01). Comparing the
      demographics of those who had TN before 1984 with those who had TN in the
      cyclosporine era shows similarities: the mean age at TN (32 versus 32 years),
      percent male (66 versus 61), percent black (51 versus 61), percent of TN
      operations within six months of graft insertion (80 versus 70) and percent
      perioperative complications (nine versus 11). During the precyclosporine era, TN
      was performed more frequently in patients who received allografts from cadavers
      versus living related donors (30 versus 8 percent, p < 0.05), but this difference
      was eliminated after 1983 (11 versus 13 percent, p = NS). TN was performed more
      frequently after secondary versus primary transplants in the early (36 versus 23
      percent) and later (23 versus 11 percent) time periods (p < 0.05 only for the
      later time period). It is also noteworthy that the rate of TN decreased
      significantly for primary and secondary transplants in the later time period. For
      low risk white patients and higher risk black patients the rate of TN decreased
      in an identical manner. We conclude that since the introduction of cyclosporine,
      TN is performed less frequently, the frequency of TN in lower risk (primary
      white) and higher risk (secondary, black, cadaveric) groups has decreased and TN
      has been and remains a safe procedure.

PMID- 8156120
TI  - Hilar lobar vascular occlusion for hepatic resection.
AB  - Limited resection can be a therapeutic approach in patients with cirrhosis with
      very low remnant hepatic function after resection. In this study, two hilar
      vascular clamping methods (hilar selective clamping [n = 13] and hilar lobar
      clamping method [n = 8]), which were used for resection of hepatocellular
      carcinoma in patients with cirrhosis, were compared based on cardiovascular
      stability during clamping, intraoperative bleeding, operative time and
      postoperative course. In the past, the Pringle method had been used (n = 19) and
      those instances were included for comparison. The mean operation time of the
      lobar clamping group was 209 +/- 41 minutes, which was significantly less than
      that of the selective clamping group (259 +/- 44 minutes, p < 0.05). Furthermore,
      the mean intraoperative blood loss of the lobar clamping group was 920 +/- 400
      milliliters, which was significantly less than that of the selective clamping
      group (1,640 +/- 590 milliliters, p < 0.01). The postoperative total bilirubin
      and glutamine-oxaloacetic transaminase levels tended to be high in the Pringle
      group, but there was no significant difference between the groups. Although the
      blood pressure during clamping significantly decreased in all groups, the
      decrease was profound in the Pringle group as compared with those in the other
      two groups. Thus, as a method for controlling afferent blood flow during hepatic
      resection in patients with cirrhosis, we recommend the lobar clamping method as a
      simple, safe and effective way to minimize bleeding and maintain cardiovascular
      stability.

PMID- 8156121
TI  - Changes in regulating blood coagulation in hepatic resection with special
      references to soluble thrombomodulin and protein C.
AB  - The protein C anticoagulant pathway in hepatic resection was studied. The
      patients were divided into two groups--group 1 consisted of patients with a
      normal liver and group 2 consisted of patients with either hepatitic or a
      cirrhotic liver. Plasma protein C activity and soluble thrombomodulin were then
      sequentially measured during hepatectomy and in the early postoperative period.
      The protein C activity in group 1 decreased during hepatectomy and reached a low
      immediately after operation, and thereafter, recovered to near preoperative
      levels. However, the preoperative value in group 2 was lower than that in group 1
      and the postoperative values were significantly lower than those in group 1 (p <
      0.05). The level of soluble thrombomodulin in group 1 decreased during
      hepatectomy but later returned to preoperative levels. However, in group 2, the
      preoperative value was higher than that in group 1 and the postoperative values
      were greater than that of the preoperative values, while the values were
      significantly higher than those in group 1 (p < 0.05). During hepatectomy,
      hypercoagulability may contribute to the low levels of protein C and soluble
      thrombomodulin. The postoperative significant increase of soluble thrombomodulin
      may, thus, indicate the occurrence of endothelial injury in the remnant liver.
      The sequential measurements of both parameters can, therefore, be useful in
      detecting coagulopathy and endothelial injury in hepatic resection.

PMID- 8156122
TI  - Pelvic promontory fixation of the vaginal vault in sixty-two patients with
      prolapse after hysterectomy.
AB  - During a 20 year study period from 1969 to 1991, 62 patients underwent abdominal
      colpopexy between a prolapsed vaginal vault and the cartilage of the promontory.
      A simple surgical operation technique introduced in 1954 was modified and tested
      on these women. Hysterectomy, either transabdominal or vaginal, had previously
      been performed upon all of these patients. In some instances, short lyodura loops
      were used to suspend the vagina. In all operations, the suspension was covered
      with peritoneum of the lumbosacral area. Functional and cosmetic results were
      excellent and urinary stress incontinence could often be improved. It is
      suggested that this type of procedure is indicated in subtotal and total prolapse
      of the vagina after hysterectomy in patients who desire to preserve sexual
      function.

PMID- 8156123
TI  - The lateral approach to the proximal popliteal artery for popliteal to anterior
      tibial artery bypass.
AB  - The exposure of the proximal popliteal artery through a lateral incision for
      bypasses to the anterior tibial artery is simple and logical. It avoids the need
      to direct the graft from the medial to the lateral side of the leg and,
      therefore, is advantageous when limited autogenous vein is available. The lesser
      saphenous vein is usually long enough to reach the most distal anterior tibial
      artery.

PMID- 8156124
TI  - A simplified technique of ex situ hepatic surgical treatment.
AB  - A simplified technique of "ex situ" hepatic surgical treatment, indicated when
      conventional operation is precluded by a huge centrohepatic tumor or the need of
      suprahepatic vascular reconstruction, or both, is described. Wide access on all
      parts of the liver is provided by section of infrahepatic and suprahepatic vena
      cava, but the continuity of the portal triad is preserved. This technical
      modification reduces the duration of the anhepatic phase and avoids the risks of
      artery and biliary reconstruction.

PMID- 8156125
TI  - Esophagectomy without thoracotomy with vagal preservation.
AB  - The techniques of vagal preservation for use in esophagectomy without thoracotomy
      are presented. The purpose of vagal preservation is to avoid the debilitating
      postvagotomy syndrome. The technique of preservation varies depending on the mode
      of esophagectomy, the primary disease and the organ selected to be used for
      esophageal reconstruction. The postoperative quality of life is improved by the
      preservation of vagal function.

PMID- 8156126
TI  - Carcinoma of the proximal bile duct.
AB  - Carcinoma of the proximal bile duct, while an uncommon disease, can present
      diagnostic and therapeutic challenges. Although frequently discovered as a small
      tumor, the disease is usually histologically advanced with microscopic
      progression along the biliary system, perineural invasion and occult involvement
      of regional lymphatics. Because of this behavior, treatment, while perhaps
      macroscopically complete, may not be curative. However, important issues need to
      be considered. Whenever possible, provided the patient is an acceptable operative
      risk, histologic confirmation of carcinoma of the bile duct should be made as
      other, sometimes benign, causes may mimic this disease. Preoperative assessment
      using contrast visualization of ductal and vascular anatomy should be undertaken
      to aid in intraoperative decisions regarding resectability, thereby selecting, as
      well as possible, patients who will benefit from potentially radical and
      hazardous surgical treatment. Palliation, in patients who are unresectable,
      should be performed either by transtumoral intubation or bypass. Adjuvant
      radiotherapy, while not clearly beneficial, should probably still be attempted in
      patients with residual disease. Chemotherapy may also be used either alone or in
      combination with radiation. The long term survival period is poor, but may be
      extended in those patients in whom complete excision of carcinoma can be
      accomplished.

PMID- 8156127
TI  - Supporting breast-feeding in women with epilepsy.

PMID- 8156128
TI  - Case studies of family dynamics.

PMID- 8156129
TI  - Concerns & fears of children with seizures.

PMID- 8156130
TI  - When a parent has epilepsy.
AB  - I have just ended year one of being a parent. Though I have presented many
      difficulties of being a parent with epilepsy, there are many more joys. The most
      important thing for nurses to remember is that a person with epilepsy can become
      a parent, often without difficulty. For others, living with epilepsy will pose
      special concerns or problems that may complicate the parenting role.

PMID- 8156131
TI  - The carer-led assessment process (CLASP): a framework for the assessment of need
      in dementia caregivers.
AB  - The initial and on-going assessment of individuals with dementia may not always
      fully reflect the expert knowledge of the caring situation that carers possess.
      In the absence of such knowledge a comprehensive and responsive assessment is
      unlikely to be achieved. This paper describes the development of a carer-led
      assessment process (CLASP) which it is suggested provides a flexible framework
      for the assessment of need in carers of dementia sufferers.

PMID- 8156132
TI  - The assessment and management of post-operative pain in children by registered
      sick children's nurses: an exploratory study.
AB  - In a small exploratory study, convenience samples of registered sick children's
      nurses (RSCNs), parents and children were interviewed to establish their
      perceptions of post-operative pain assessment and management. Many of the
      findings of previous researchers were confirmed. Nurses and parents made
      judgements of pain using behavioural cues. The administration of analgesia
      depended on the nurse's personal interpretation of the prescription. The efficacy
      of analgesia was influenced by the organization of nursing care.

PMID- 8156133
TI  - When a vulnerable patient absconds.
AB  - This case-study examines the nurse's role when a patient at risk absconds. It
      highlights possible weaknesses in the system for dealing with absconding patients
      who are so cognitively and emotionally impaired, that they may present a danger
      to themselves. The issues of patient identification and stigmatization are raised
      along with the possible conflict this may cause in psychiatric nurses.
      Recommendations for care at ward level are made, including asking the vulnerable
      patient to wear an identity bracelet and the instigation of a prepared action
      plan which involves engaging the help of outside agencies should a patient
      abscond.

PMID- 8156134
TI  - The management and development of continence services within the framework of the
      NHS and Community Care Act (1990).
AB  - The current context of community health care is described and the main issues
      concerning the development of continuity of care for the handicapped and elderly
      raised. Changes in philosophical and governmental approaches have coincided at a
      time of demographic changes that is resulting in increased numbers of elderly.
      Continence services are used as a vehicle in order to demonstrate the need for
      protocols, systems and evaluation measures across community care team boundaries.
      Current government decisions and reports are interwoven within the text with
      professional considerations and other requirements for decision making. The
      proactive approach offered in this paper for continence services, is also seen as
      important to other specialist services, such as stoma and diabetes care so that
      standards of patient care are improved--these being evaluated by approved quality
      care tools.

PMID- 8156135
TI  - Integrating research, education and practice in nursing.

PMID- 8156136
TI  - Nuances of reflection.

PMID- 8156137
TI  - An evaluation of self-administration of medicines on a rheumatology ward.

PMID- 8156138
TI  - How to choose: nurses' judgements of the effectiveness of a range of currently
      marketed continence aids.
AB  - Continence is a costly health problem, both in terms of financial burden in
      continence aids, but also in terms of quality-of-life issues for the person who
      has continence problems. Manufacturers are often perturbed as to why products
      specially designed to help continence problems are not popular, or do not appear
      to be applied as intended. This paper reports on a study involving a quantitative
      evaluation of a range of continence aids presently being marketed, as applied in
      a large elderly care centre. The evaluation used nursing judgements on a series
      of comfort and effectiveness criteria: amount of leakage around the pad, comfort
      to the client when the pad was either wet or dry, skin integrity and snugness of
      fit, as well as whether the pad concealed well beneath clothing. Five body pads
      were evaluated--two disposable and three washable--and three bed under-sheets.
      Effectiveness of pads was found to vary substantially according to sex of client
      and voiding type, that is whether the client had heavy or moderate incontinent
      episodes.

PMID- 8156139
TI  - Sexual harassment of nurses: an occupational hazard?
AB  - A questionnaire was administered to qualified and student nurses to assess the
      prevalence and consequences of sexual harassment. There was a 56% completion
      rate. Of these 43 (66%) of the registered nurses and nine (35%) of the student
      nurses reported having experienced sexual harassment. The incidence of harassment
      for registered nurses in the year prior to the study was 46%. Patients were most
      likely to be the harasser for both student and registered nurses but there was an
      increased likelihood that other staff were involved in the harassment of
      registered nurses with doctors and male nursing staff being the predominant
      perpetrators. Dimensions of assertiveness and sex role identity did not predict
      the likelihood of harassment. Results are discussed in the context of attribution
      theory and gender power relationships.

PMID- 8156140
TI  - Student midwives' learning experience on the wards.
AB  - This paper is based on an investigation into the learning experiences of student
      midwives in the clinical setting in one maternity unit in the Republic of
      Ireland. A questionnaire approach was adopted for the data collection and 42
      student midwives participated in the study. A number of factors were identified
      which appear to influence students' experiences of 'learning on the job'. The
      quality of their clinical teaching and their observations of the way in which
      trained staff practise midwifery may influence their decision to continue
      practising midwifery following registration. These findings clearly point to the
      importance for midwives to reassert their true role as 'independent
      practitioners' of normal maternity care.

PMID- 8156141
TI  - Idiopathic inflammatory myopathies: clinical aspects.

PMID- 8156142
TI  - Pathology of the inflammatory myopathies.
AB  - Careful examination of muscle biopsy specimens is indispensable in the diagnostic
      work-up of patients whose clinical picture is suggestive of or consistent with an
      inflammatory myopathy. Pathological diagnosis can, in the vast majority of cases,
      determine the specific type of inflammatory myopathy which is of paramount
      importance for prognosis and therapy. The pathological study of muscle has also
      been useful to reveal information pertaining to the pathogenesis of the different
      entities and ultimately it may also lead us to the precise aetiology.

PMID- 8156143
TI  - Inclusion body myositis.
AB  - IBM has emerged as a clinicopathological entity during the past 25 years but with
      increasing complexity. It occurs primarily in elderly persons (over the sixth
      decade of life, with 3:1 male preponderance), but young adults or children may
      also be affected in some families. FIBM is by and large non-inflammatory though
      some autosomal dominant FIBM cases have inflammatory cell infiltrates. In IBM,
      slowly progressive weakness of proximal as well as distal muscle groups occurs
      and is usually not associated with skin rash or malignancy. The incidence of
      associated collagen-vascular disease is thought to be lower than in DM or PM but
      is reported to be as high as 15%. It is generally refractory to treatment with
      corticosteroids or other immunosuppressants. Muscle biopsy and electromyography
      may suggest a neurogenic process mixed with myopathic features. None of the
      histopathological features is specific enough to be a diagnostic criterion. The
      diagnostic criteria have to be collective, encompassing both clinical and
      pathological criteria in different combinations. The presence of eosinophilic
      intranuclear or cytoplasmic inclusions immunoreactive for both beta-amyloid and
      ubiquitin in affected myofibres may facilitate the diagnosis of IBM. The
      diagnosis no longer depends on the ultrastructural demonstration of
      characteristic microtubular filaments as previously thought. The identification
      of both beta-amyloid and ubiquitin may provide a new concept for the disease
      process in IBM. A chronic persistent intracytoplasmic synthesis of abnormal
      amyloid protein in IBM is suspected to be similar to that in Alzheimer's disease.
      IBM is considered to be intimately related to a heterogenous group of non
      inflammatory IBMD, including DMY, OPMD, and both autosomal recessive and dominant
      FIBM. An inflammatory response has been seen, however, in muscles of both OPMD
      and autosomal dominant FIBM. The pathogenesis in IBM and in IBMD may not be the
      same. Unlike IBM, there is no abnormal sarcolemmal expression of MHC-I antigen in
      IBMD as a sign of T-cell-mediated cytotoxicity causing myofibre destruction. The
      prion theory derived from identification of amyloidogenic protein in the filament
      inclusions in the rimmed vacuoles is provocative. If one believes in the
      contention that the amyloidogenic filaments are the primary pathogen of either
      IBM or IBMD, one must account for the fact that these filaments are originally
      derived from sarcolemmal nuclei and not from autophagic vacuoles. Until this is
      clarified, the possibility that the filaments represent either abnormal or
      defective 'slow' virus nucleocapsids cannot be completely ruled out.

PMID- 8156144
TI  - Immunogenetics of inflammatory myopathies.
AB  - The genes most commonly considered when investigating immunogenetic associations
      with autoimmune diseases, including inflammatory muscle disease (IMD), are those
      encoded in the major histocompatibility complex (MHC), the T-cell receptor (TCR)
      genes and the immunoglobulin genes. In caucasoids HLA DR3 is associated with
      adult polymyositis (PM) and juvenile dermatomyositis (JDM) and is probably
      increased in frequency in adult DM. In inclusion body myositis (IBM) DR3 and DR1
      have been separately reported to be increased but few patients have been
      analysed. The DR3 in IMD is almost always present on the ancestral haplotype
      marked by HLA-B8, C4A*Q0 and DR3 and presumably accounts for the association with
      C4A*Q0 which has been reported in some subgroups of IMD. In other races the
      associations are less clear although DR6 may be increased in blacks with PM. In
      PM, DR3 is strongly associated with the presence of antibodies to histidyl tRNA
      synthetase (Jo-1). DR52 is even more strongly associated with the presence of
      this autoantibody and this association can be demonstrated in black and white
      patients. It is unlikely that DR3 is associated with autoantibodies to other
      aminoacyl-tRNA synthetases or signal recognition proteins although fewer cases
      have been reported and racial differences may exist. Antibodies to the Pm-Scl
      antigen are also associated with DR3 while autoantibodies to Mi-2 may be
      associated with DR53. In caucasoids DR4 was increased in D-penicillamine induced
      IMD but again there may be inter-racial differences. Amongst caucasoids with
      mixed connective tissue disease (MCTD) there is an increased frequency of DR4 and
      this allele is associated with the development of antibodies to ribonucleoprotein
      (RNP). In other races the data are minimal. Very few investigations of
      associations between TCR polymorphisms or immunoglobulin allotypes and IMD have
      been reported. The phenotype Gm 3;5 has been associated with PM in caucasoids and
      may interact with DR3 in predisposing to disease. The Gm phenotype 1,3;5,21 has
      been associated with MCTD and with the development of anti-RNP, with or without
      MCTD, in caucasoids. Multiple genetic factors are likely to determine the
      development of IMD and the particular combination of alleles at predisposing loci
      may differ between races and according to the inducing agent. Furthermore, the
      predisposing genetic factors may vary between subgroups of IMD.

PMID- 8156145
TI  - Cellular mechanisms in inflammatory myopathies.
AB  - Cell-mediated immune mechanisms play a prominent role in inclusion body myositis
      (IBM) and polymyositis (PM). In both IBM and PM, CD8+ cytotoxic T cells
      expressing the alpha/beta receptor surround and focally invade non-necrotic
      muscle fibres. This lesion can be considered the hallmark of cell-mediated
      myocytotoxicity. Essentially the same type of lesion is observed in a variant
      form of PM, in which CD4-CD8- T cells bearing the gamma/delta receptor surround
      and invade non-necrotic muscle fibres. In both IBM and PM, all of the invaded and
      some of the non-invaded muscle fibres strongly express HLA class I molecules.
      This is consistent with the hypothesis that the CD8+ autoinvasive cytotoxic T
      cells recognize antigenic peptide(s) bound to HLA class I molecules on the muscle
      fibre surface. According to the rules of antigen processing, these peptides
      derive from proteins synthesized in the muscle fibre. Theoretically, the proteins
      could be viral components or self proteins that resemble viral components. Most
      attempts to demonstrate viral antigens or genome in muscle fibres have failed. On
      the other hand, the majority of HLA class I molecules expressed on the surface of
      any cell are loaded with endogenous self peptides. It seems plausible that muscle
      specific autoantigen(s) could be recognized by autoaggressive T cells in the
      inflammatory myopathies, but the precise reasons for the recognition event
      remains elusive. Recently, it has become possible to study the interactions of
      muscle cells and cytotoxic effector cells in vitro. Myoblasts and myotubes can be
      induced to express a variety of immunologically relevant histocompatibility and
      cell adhesion molecules. Myotubes are highly susceptible to lysis by allogeneic
      CD8+ cytotoxic T cells sensitized against HLA class I alloantigens.
      Interestingly, cultured myotubes are also susceptible to lysis by antigen
      nonspecific natural killer cells. Further, myoblasts stimulated by IFN gamma
      express HLA class II and acquire the full potential to process and present
      complex protein antigens to CD4+ T cells. This may indicate that myoblasts can
      actively participate in local immune reactions by presenting (auto) antigens to
      helper/inducer T cells. In different inflammatory myopathies, CD8+ T cells have
      been expanded directly from muscle and their interactions with autologous
      myotubes have been investigated in vitro. In several cases, a low but significant
      autoreactive cytotoxic effect was observed. This is consistent with the
      hypothesis that some cytotoxic effector T cells recognize an autoantigen on
      myotubes. One of the major goals for future studies is to define the autoantigens
      that are relevant in the pathogenesis of the inflammatory myopathies.

PMID- 8156146
TI  - The role of viral infection in polymyositis, dermatomyositis and chronic fatigue
      syndrome.

PMID- 8156147
TI  - Retroviruses and inflammatory myopathies in humans and primates.
AB  - The human immunodeficiency virus (HIV), the human T cell lymphotropic virus (HTLV
      1), the human foamy retrovirus and the simian immunodeficiency viruses have been
      associated with the development of an inflammatory myopathy in humans and
      primates. The myopathy caused by HIV and HTLV-1 is not due to direct infection of
      the muscle by these viruses, but rather due to an immunopathologic process
      triggered by the viruses, mediated by autoaggressive CD8+ cells in the context of
      MHC-class I antigen expression. This has been based on a series of studies
      utilizing immunocytochemistry, in situ hybridization, polymerase chain reaction,
      and co-cultivation of human myotubes with the viruses or with HIV-1 and HTLV-1
      infected homologous lymphoid cells. Because the clinical, histological and
      immunological picture of patients with retroviral-associated inflammatory
      myopathies is identical to that of patients with retroviral-negative inflammatory
      myopathy, there is a reasonable possibility that retroviruses may be candidate
      viruses in triggering inflammatory myopathies. In recent years, the
      antiretroviral drug AZT (Zidovudine), commonly used for the treatment of AIDS,
      has been shown to cause a distinct mitochondrial myopathy characterized by
      depletion of the muscle mitochondrial DNA due to AZT's ability to inhibit the
      gamma-DNA polymerase of the mitochondrial matrix. Distinction of the AZT-myopathy
      is clinically important because it responds to discontinuation of AZT and to
      administration of another antiretroviral agent such as ddI or ddC.

PMID- 8156148
TI  - Experimental models of inflammatory myopathies.
AB  - Several animal models of inflammatory myopathy have been discussed in this
      review. These include autoimmune (by immunization with muscle antigen and
      adjuvant), viral-induced, and spontaneous forms. The autoimmune and viral-induced
      models have limitations as models of the human disorders but because they are
      relatively well-characterized still have merit in studying immune effector
      mechanisms of muscle injury. The spontaneous models are less well-characterized,
      but may nevertheless provide insight into the induction mechanisms of
      inflammatory muscle diseases. All of these animal models have the potential to
      provide valuable information which will improve our understanding of the
      pathogenesis of the human inflammatory myopathies.

PMID- 8156149
TI  - Treatment of inflammatory myopathies.
AB  - Although there have been considerable advances in our understanding of the
      immunopathogenesis of the different forms of autoimmune inflammatory myopathy,
      the treatment of these conditions remains largely empirical, being based upon the
      use of immunosuppressive and immunomodulatory therapies which, for the most part,
      are non-selective in their actions. Corticosteroids are usually effective in
      adult and childhood cases of polymyositis and dermatomyositis, but are only
      rarely helpful in inclusion body myositis, which is usually also unresponsive to
      other forms of immunosuppressive therapy. Alternate-day corticosteroid therapy
      has a role in patients with mild disease and as a means of minimizing the side
      effects of steroids. This may also be achieved by the early introduction of a
      second-line agent such as methotrexate or azathioprine, which will allow more
      rapid steroid withdrawal and may also improve the chances of inducing a remission
      in more severe cases. In patients who fail to respond adequately to oral
      corticosteroids, or who relapse after an initial response, intravenous
      immunoglobulin therapy or pulse therapy with intravenous methylprednisolone are
      promising approaches which appeal as safer alternatives to cytotoxic drugs.
      However these forms of treatment will require further evaluation in prospective
      clinical trials. The same applies to cyclosporin, which has a more selective
      action on T cells, and which has been reported to be effective in resistant cases
      of adult and juvenile polymyositis and dermatomyositis. In the longer term, the
      development of more specific forms of immunotherapy for these myopathies, aimed
      at blocking autoantigen presentation or its interaction with T cells, awaits the
      identification of the target antigens and T cells which initiate the autoimmune
      process.

PMID- 8156150
TI  - What is the Institute?

PMID- 8156151
TI  - Reduction in the incidence of postradiation dental complications in cancer
      patients by continuous quality improvement techniques.
AB  - The major dental consequences of radiation treatment to the head and neck are
      reviewed, and the role of the dentist in the management of these patients
      outlined. By using a concurrent patient data base and integrating quality
      assurance (clinical indicators) and quality improvement, a clinical department
      demonstrates how the risk of dental morbidity can be identified and reduced.

PMID- 8156152
TI  - Measuring quality of life: apparent benefits, potential concerns.
AB  - Quality of life (QOL) research is reviewed in relation to measurement issues and
      applications to decision-making. Multidimensional standardized questionnaires
      provide assessments of different aspects of health-related QOL, including
      psychological, physical and social functioning as well as symptoms. Formal QOL
      assessments provide systematic, quantitative answers to the kinds of questions
      clinicians usually ask informally, such as "how have you been lately?" QOL
      measurements have various uses at different levels of decision-making, from the
      micro (individual) to the macro (population) level. Examples are applications to
      clinical trials and to studies of patients' needs for care. Clinical trials have
      already provided an unexpected result--for patients with advanced disease,
      pretreatment QOL may predict survival outcome. Such results provide evidence for
      the validity of QOL measurements, but also raise ethical issues that must be
      recognized and addressed.

PMID- 8156153
TI  - Synaptic patterns of rye B chromosomes. I: The standard type.
AB  - Chromosome pairing of standard B chromosomes (Bs) in rye has been studied by
      synaptonemal complex surface spreading of pollen mother cells containing from one
      to eight Bs. The main characteristics exhibited by the Bs are: (i) They are often
      located peripherally in surface spread nuclei and do not show presynaptic
      alignment. (ii) The period of pairing is delayed relative to that of the A set.
      (iii) Bs undergo extensive non-homol-ogous pairing at pachytene. (iv) The
      frequency of trivalents and quadrivalents in plants with 3Bs and 4Bs is about 66%
      following the expectations on the basis of random pairing among the short and the
      long arms with a single distal pairing initiation site per arm. Some
      quadrivalents containing two partner switches were observed, but on the same
      basis of randomness there was a deficiency of pachytene multivalents in plants
      with 5-8 Bs. The possible causes of the discrepancy between these observations
      are discussed. (v) There is a reduction in the frequency of multivalents between
      pachytene and metaphase I.

PMID- 8156154
TI  - Avian sex chromosomes in the lampbrush form: the ZW lampbrush bivalents from six
      species of bird.
AB  - The ZW bivalent has been identified and characterized in detail in its lampbrush
      form in oocytes of chicken, quail, turkey, pigeon, chaffinch and sparrow. The sex
      bivalent in all six species looks like a single highly asymmetrical chromosome.
      Most of it has the typical lampbrush organization. The terminal one-fifth is
      relatively thick and condensed and bears only a few pairs of lateral loops: this
      condensed terminal region is the W chromosome; the part with normal lampbrush
      morphology is the Z. The two are connected by a single near terminal chiasma. The
      fine scale morphology and arrangement of loops and markers on Z and W chromosomes
      are described for each species and lampbrush maps have been constructed. The
      identification of the lampbrush sex bivalent is based on the following criteria.
      The asymmetrical chromosome has two centromere regions. In the interstitial
      region of the asymmetrical chromosome where the junction between Z and W
      chromosomes is supposed to be, there are telomere-specific loops and telomeric
      DNA sequences and there is good morphological evidence for the presence of a
      chiasma. There are W chromosome specific DNA sequences in the region of the
      asymmetrical lampbrush chromosome that is thought to represent the W. Breed
      specific variations in the morphology of the chicken W chromosome with respect to
      the sizes, numbers and arrangements of axial chromomeres and distributions of
      specified repeated DNA sequence families have been identified, offering one of
      the first examples of definitive correlation between a repeat family and a single
      chromomere. The lampbrush chromosomes of all the birds examined, except quail,
      terminate in distinctive free hanging loops. These are a novel feature in the
      sense that at the end of each chromatid there is a large transcription unit
      terminating in a cluster of telomeric DNA sequences.

PMID- 8156155
TI  - Localization of tandemly repeated DNA sequences in beetle chromosomes by
      fluorescent in situ hybridization.
AB  - In situ hybridization to chromosomes and nuclei of Tenebrio molitor shows the
      massive presence of a species-specific satellite DNA in all chromosomes and six
      sites of rDNA in mitotic chromosomes. These sites are located in two autosomal
      pairs and in the X and Y chromosomes. In a related species, Misolampus goudoti,
      in which two different families of highly repetitive DNA have been previously
      characterized, one family is located in centromeric regions of all chromosomes
      with the exception of chromosome Y, while the other repeated DNA family is
      present both in centromeric and distal regions of all chromosomes. rRNA genes in
      this species are present in a medium-sized autosomal pair only. These results
      show that molecular cytogenetics can be applied to coleopteran chromosomes and
      open the way for a physical mapping of DNA sequences in these organisms. The
      results also provide insights into the type of meiotic association of the X and Y
      chromosomes in Coleoptera and the distribution of repeated DNAs within the genome
      of these insects.

PMID- 8156156
TI  - Synaptonemal polycomplexes in spermatids: a characteristic trait of Orthoptera?
AB  - Spermatogenesis was analysed in a cricket, Eneoptera surinamensis (Gryllidae,
      Orthoptera), using ultrathin serial sections and transmission electron
      microscopy. Special attention was placed on documentation of the development and
      structure of synaptonemal polycomplexes (PCs) within spermatid nuclei. Pachytene
      spermatocytes showed the usual tripartite synaptonemal complexes in the nuclear
      lumen. PCs were situated close to chromosomes at the periphery of spindles in
      prometaphase I spermatocytes, where microtubule density was low. The PCs are
      probably incorporated into the daughter nuclei of both meiotic divisions by
      adhesion to chromosomes. Finally, PCs end up within spermatid nuclei. Analysis of
      serial sections through three nuclei of young spermatids revealed at least one PC
      within each. The PCs were intimately attached to an electron-dense spherical
      nuclear body. This topographical correlation was confirmed through inspection of
      random sections. The PCs may have an affinity to the spherical bodies. In more
      developed spermatids, PCs and nuclear bodies were missing. Disassembly products
      of the PCs may play a role in spermatid maturation. In a series of other
      Orthoptera species, PCs have been reported to occur in the cytoplasm or the
      nuclei of spermatids. In most other systematic groups, PCs do not form at all or
      disassemble earlier. The presence of PCs in young spermatids, therefore, seems to
      be typical of Orthoptera.

PMID- 8156157
TI  - Computer-aided automatic identification of rice chromosomes by image parameters.
AB  - An automatic, computer-aided method for identification of rice chromosomes was
      developed based on image parameters obtained by image analysis. Numerical data of
      the 360 condensation patterns (CPs) or the density profiles of rice chromosomes
      obtained from 30 chromosomal spreads of haploid rice were subjected to three
      different discrimination methods for identifying the chromosome: (1)
      discrimination flow chart, (2) linear discrimination functions, and (3) minimum
      distance classifier based on standardized Euclidean distance. Discrimination
      based on the minimum distance classifier resulted in the correct identification
      of more than 92% of the rice chromosomes. The first and second methods gave a
      correct identification of 91% and 84%, respectively. It is concluded that the 12
      rice chromosomes in most spreads could be identified by a computer.

PMID- 8156158
TI  - Synaptonemal complex karyotyping: an appraisal based on a study of Crepis
      capillaris.
AB  - A synaptonemal complex (SC) karyotype for Crepis capillaris, based on SC
      measurements from 92 surface-spread pachytene nuclei, was compared with the
      mitotic karyotype of this species in order to evaluate the specific and general
      validity of SC karyotyping and to assess its potential for high resolution
      physical mapping. Although there are obvious similarities between the SC and
      mitotic karyotypes of Crepis capillaris, detailed quantitative comparisons reveal
      that they differ in some respects, both with regard to the relative lengths of
      entire chromosomes and arm ratios. The arm ratio differences between SC and
      mitotic chromosomes are evident in both the A and C chromosomes and reflect the
      distribution of C-banding heterochromatin. Based on this comparison,
      heterochromatin appears to be underrepresented in SC length. However, the
      relative lengths of entire A and C chromosome SCs do not conform to this model
      and suggest that some other factor or factors are also influencing SC lengths
      differentially. It is concluded that the non-agreement of SC and mitotic
      karyotypes does not invalidate the use of SCs for karyotyping and physical
      mapping purposes provided that any differences are understood and characterized
      as far as possible.

PMID- 8156159
TI  - Oocytes from pachytene to dictyotene can easily be analysed in neonatal rodents.
AB  - We have investigated the dynamics of meiotic prophase I in neonatal ovaries from
      different wild rodent species, from a laboratory strain of Mus musculus and from
      Mus musculus x Mus spretus F1 hybrids. We found that almost all stages of
      prophase I were regularly present in neonatal ovaries from these species and that
      their transcriptional activity can be assessed by [3H]-uridine incorporation,
      indicating that postnatal analysis of meiotic chromosomes and synapsis may be
      conducted as an alternative to the investigation of foetal ovaries.

PMID- 8156161
TI  - Scanning electron microscopy of polytene chromosomes (I).
AB  - The structure of polytene chromosomes has been observed by conventional scanning
      electron microscopy and also with a high resolution 'in lens' field emission
      instrument. Surface imaging with secondary electron emission has characterized
      condensed chromatin and regions known for their RNA synthetic potential
      (nucleoli, Balbiani rings and puffs). In DNA-rich bands pairing of chromatids
      appears so perfect that individual chromomeres cannot be visualized as discrete
      units. In the interbands only chromatid bundles appear as elements, but not
      individual chromatids. High resolution scanning electron microscopy allows
      resolution at the nucleosome level. Improved localization of chromosomal
      structures is demonstrated, as in the case of the proposed separation of the
      prepupal 'Balbiani ring 1'. Surface images of the RNA synthetic centres of the
      salivary gland cell are presented. Transcripts of the Balbiani ring template can
      be observed in the condensed and gradually unfolded state, allowing measurement
      of unit ribonucleoparticles. The surfaces of puffs have been visualized and are
      characterized by multiple supercoiled loop structures, which are described
      according to size, conformation and distribution.

PMID- 8156160
TI  - The genomic synteny at DNA level between human and chimpanzee chromosomes.
AB  - The evolutionary relationship between human (Homo sapiens) and chimpanzee (Pan
      troglodytes) has been the subject of debate and scrutiny for over two decades.
      The close relationship established by numerous parameters may or may not reflect
      homology at the DNA level. The recent advent of a molecular method termed the
      chromosome in situ suppression hybridization (CISS)-technique has prompted us to
      explore the phylogenetic relationship at the DNA sequence level. Cross
      hybridization data using human-derived whole chromosome paints (WCPs) suggests an
      apparent genomic synteny with chimpanzee chromosomes at the DNA level, thus
      providing a better understanding of an evolutionary relationship between humans
      and chimpanzees.

PMID- 8156162
TI  - Identification and localization of two genes on the chicken Z chromosome:
      implication of evolutionary conservation of the Z chromosome among avian species.
AB  - A cDNA clone containing an insert of about 3.4 kb, pCIREBP, was isolated from the
      chicken liver cDNA library and identified as a clone for the chicken homologue of
      iron-responsive element-binding protein (IREBP). The deduced amino acid sequence
      showed 88% identity with that of the mouse IREBP and 17 out of the 20 active site
      residues of the pig heart mitochondrial aconitase were conserved. Another cDNA
      clone, pZOV3, containing an insert of about 4.5 kb was isolated from the chicken
      ovary cDNA library. This cDNA contained an open reading frame for 327 amino acid
      residues, whose sequence had partial similarity to two immunoglobulin superfamily
      proteins; mouse GP-70 and chicken HT7. Fluorescence in situ hybridization using
      corresponding genomic clones revealed that both genes are localized on the Z
      chromosome; the ZOV3 gene at the middle of the short arm and the IREBP gene at
      the boundary of heterochromatin on the long arm. Southern blot hybridization to
      male and female genomic DNA preparations from six species representing five avian
      genera suggested that these two genes are Z-linked in all the species tested.

PMID- 8156163
TI  - Chromosomal localization of the lysozyme gene cluster in river buffalo (Bubalus
      bubalis L.).
AB  - Lysozyme (LYZ) is an antibacterial enzyme which allows the digestion of bacteria
      present in tears and saliva. In the true stomach of ruminants LYZ breaks open the
      bacteria of the foregut, which are subsequently digested by typical mammalian
      digestive enzymes, allowing the incorporation of nutrients from the bacteria.
      Southern analysis with a single exon from a cow lysozyme gene revealed that there
      are about 10 genes in ruminants (Irwin & Wilson 1989), while pig and primates
      have a single lysozyme gene (Swanson et al. 1991) and camels have two (Irwin et
      al. 1992). The higher number of LYZ genes in ruminants is believed to be the
      result of gene duplication associated with the evolution of foregut fermentation
      (Irwin et al. 1992). Recently, the genomic organization of the lysozyme gene
      family has been determined in domestic cattle, and, using a cocktail of genomic
      clones, the lysozyme gene cluster (LYZ/) was assigned to chromosome (Chr) 5, band
      23 by fluorescence in situ hybridization (FISH) (Gallagher et al. 1993). In our
      continued effort to test the genetic homology of conserved chromosome banding
      regions between cattle and river buffalo, and to extend the river buffalo
      physical gene map, we have mapped the LYZ/ by FISH and R-banding.

PMID- 8156164
TI  - MULTIPRINS: a method for multicolour primed in situ labelling.
AB  - With this fast and simple MULTIPRINS protocol we show simultaneous mapping of
      multiple repetitive sequences by sequential cycles of primed in situ (PRINS)
      labelling with various primers and reporter molecules. Differentially labelled
      DNA sequences synthesized in situ were visualized by directly incorporated
      rhodamine-4-dUTP, by fluorescein isothiocyanate and Cy5 using digital imaging
      microscopy. This further development of the PRINS method enhances its potential
      as an alternative to traditional in situ hybridization.

PMID- 8156165
TI  - Detection of Propionibacterium acnes polypeptides which have stimulated an immune
      response in acne patients but not in normal individuals.
AB  - Patient and normal volunteer sera were used as probes in two-dimensional PAGE of
      P. acnes culture supernatant fluid and cell extracts to determine whether
      specific P. acnes polypeptides were associated with the immune reaction in acne.
      Eight polypeptides, M(r) 20 to 131 x 10(3), pI 4.7 to 6.5 in the cell extract,
      and 7 polypeptides M(r) 10 to 24 kD, pI 4.8 to 7.5 in the culture supernatant
      fluid were specifically highlighted by patient sera and not volunteer sera. These
      polypeptides were not related to described extracellular enzymes of P. acnes. It
      is possible that these polypeptides are involved in the induction of acne.

PMID- 8156166
TI  - Inhibition of melanoma cell directional migration in vitro via different cellular
      targets.
AB  - In malignant melanoma active movement of cancer cells is considered to be
      essential for tissue invasion. Various mechanisms, such as the Ca(2+)-calmodulin
      proteinkinase C cascade or G-protein-dependent processes are considered to play a
      role in tumor cell functions. The assay of directional migration, combined with
      computer-assisted image analysis, was used to evaluate the antimigratory efficacy
      of drugs interfering with different steps of signal transduction pathways.
      Treatment with different compounds showed a more or less concentration-dependent
      reduction of migration rates: The Ca(2+)-channel blockers verapamil and devapamil
      showed a slight reduction of motility. The effect was more pronounced when the
      calmodulin antagonist flunarizine was used or the proteinkinase C inhibitors
      dequalinium, tamoxifen and H-7 were applied. A marked inhibition of motility was
      found with the G-protein antagonist L 651582. Thus, our results indicate that
      different signal transduction pathways are involved in the regulation of
      directional migration of K1735-M2 melanoma cells.

PMID- 8156167
TI  - Proteolytic activity in leg ulcer exudate.
AB  - Twenty-five leg ulcer exudate samples from 17 patients with chronic non-healing
      venous leg ulcer were analyzed for proteolytic activity using radial caseinolysis
      procedures and zymographic analysis, and for fibronectin fragmentation using
      immunoblotting technology. Caseinolytic activity was detected in 21 of the 25
      samples. A minority of them were inhibited (3 were totally, 6 partially
      inhibited) by aprotinin, a serine proteinase inhibitor, suggesting that
      proteinase(s) other than plasmin were also responsible for the caseinolysis. In
      zymographic analysis, 23 of the 25 samples showed positive reactions for enzyme
      activities comigrating with plasmin and urokinase-type plasminogen activator.
      Fibronectin fragmentation, another sign of proteolytic activity, was seen in all
      but 2 ulcers. No correlation was seen between bacterial infection or inflammatory
      cells and the above parameters in the wound fluid. Acute wound fluid collected
      from the donor sites of patients undergoing split skin grafting was used as a
      control. In the control specimens no proteolytic activity was found during the
      days following operation. These results show that there is proteolytic activity
      in the chronic ulcer exudate and support the possibility that the proteolytic
      activity and consequent fibronectin fragmentation may be related to the retarded
      epithelization and ulcer healing.

PMID- 8156168
TI  - Patterns of cell death: the significance of apoptosis for dermatology.
AB  - Development, function, remodelling, and senescence of multicellular organisms
      depend on the coordinated occurrence of physiological, actively induced cell
      death in two major patterns: terminal differentiation and programmed cell death
      (apoptosis). Apoptosis is a highly selective form of "cell suicide" with
      characteristic morphological and biochemical features: chromatin condensation,
      formation of apoptotic bodies, and DNA fragmentation by activation of
      endonucleases. Here, we outline the current understanding of apoptosis and its
      subtypes, discuss their biological functions, and delineate why apoptosis is
      relevant to the skin and its diseases. We distinguish apoptosis from necrosis,
      and discuss the regulation of apoptosis by selected genes, hormones, growth
      factors and cytokines. The epidermis and the regressing hair follicle offer
      interesting models for studying the as yet ill-understood biology of epithelial
      cell apoptosis. The selective manipulation of cell death programs may become part
      of the therapeutic arsenal of clinical dermatology.

PMID- 8156169
TI  - Distribution of monohydroxy fatty acids in specific human epidermal
      phospholipids.
AB  - Monohydroxy derivatives of polyunsaturated fatty acids such as arachidonic acid
      (AA) and linoleic acid (LA) can modulate inflammation and epidermal
      proliferation. The purpose of this study was to determine the in vivo
      distribution of the AA derivatives; 12- and 15-hydroxyeicosatetraenoic acid (12
      HETE and 15-HETE) and the LA derivatives; 9- and 13-hydroxyotadecadienoic acid (9
      HODE and 13-HODE) in specific phospholipids of normal human skin. Lipids were
      extracted from 6 normal keratome skin biopsies and phospholipids were separated
      into the major classes by two-dimensional thin layer chromatography. Monohydroxy
      fatty acids (MHFAs) released from specific phospholipids after treatment with
      phospholipase A2 were identified by reversed phase and straight phase high
      performance liquid chromatography and UV-absorption spectra. Unesterified MHFAs
      were determined in a similar way. 9-HODE, 13-HODE and 15-HETE were detectable in
      phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine
      (PE). Interestingly, 12-HETE was not detectable in these phospholipids, although
      the unesterified 12-HETE was detectable in amounts similar to unesterified 15
      HETE. Esterified 15-HETE was equally distributed between PI and PC, in which 15
      HETE was predominant, accounting for 60% and 69% of the total MHFAs, respectively
      (p < 0.05). These results demonstrate that the LA derivatives 9-HODE and 13-HODE,
      as well as the AA derivative 15-HETE, are esterified to PC, PI and PE of normal
      human epidermis in vivo. The possibility remains that 9-HODE, 13-HODE and 15
      HETE, may mediate their biological effects by being incorporated into specific
      phospholipids.

PMID- 8156170
TI  - T-cell receptor gene rearrangement studies as a diagnostic tool in
      lymphoproliferative skin diseases.
AB  - The growth of our knowledge in T-cell biology, in particular the molecular
      biology of the T-cell receptor (TCR), has provided a means to molecularly
      characterize lymphoproliferative diseases of the skin based on the presence or
      absence of a clonal population of T lymphocytes. TCR gene rearrangement studies,
      by Southern blot analysis, have aided the investigative dermatologist in gaining
      insights into the pathogenesis and clonal evolution of lymphoproliferative skin
      diseases. In addition, the application of TCR gene rearrangement studies as a
      diagnostic aid in the evaluation of lymphoproliferative skin diseases has been
      introduced into clinical dermatology. Despite its enormous research value, TCR
      gene rearrangement studies presently have limited applications as an independent
      diagnostic tool. However, as our knowledge and experience grows and as the
      application of new techniques provides us with greater detection sensitivity and
      specificity, the diagnostic utility of TCR gene rearrangement studies will be
      enhanced.

PMID- 8156171
TI  - Mechanism in allergic contact dermatitis.

PMID- 8156172
TI  - Enhancing effect of protein A on the interaction between opsonized corneocytes
      and neutrophils in staphylococcal infection.
AB  - Formation of subcorneal pustules characterizes skin lesions infected by
      Staphylococcus aureus. To elucidate the mechanism underlying the subcorneal
      pustule formation as well as that of anti-bacterial host defence, we studied the
      effect of staphylococcal protein A on the interaction between the stratum corneum
      (SC) and neutrophils. We found that protein A significantly promoted opsonized SC
      induced chemiluminescence (CL) in neutrophils. This was specific to SC because no
      enhancement was observed with opsonized zymosan. It took place even with the
      serum obtained from a patient with agammaglobulinemia, ruling out the possibility
      of the involvement of Fc-receptors of neutrophils in this phenomenon. Microscopic
      observation of such SC revealed an increase in the number of neutrophils adhering
      to the surface of the protein A-coated corneocytes. Ultrastructural observation
      showed a distinct deformation of the neutrophils adhering to the surface of the
      corneocytes, suggesting that they are in an activated state. Such an enhanced
      interaction between protein A-attached SC and neutrophils seems to play an
      important role in the host defence mechanism against the invading S. aureus and
      in the production of the characteristic pustules by the neutrophil-mediated
      damage of the surrounding epidermal tissue.

PMID- 8156173
TI  - Chemical carcinogens increase IL-1 alpha and IL-6 gene transcripts in human
      keratinocytes.
AB  - Using reverse transcriptase-linked polymerase chain reaction, the effect of
      polycyclic aromatic hydrocarbons (PAHs) on IL-1 alpha, IL-1 beta and IL-6 gene
      expression in cultured human keratinocytes was studied. Exposure to beta
      naphthoflavone and benz(a)anthracene resulted in a higher copy number of IL-1
      alpha and IL-6 mRNA while lower level of IL-1 beta mRNA was detected in these
      cells. These data suggest that, like ultraviolet B (UVB) radiation, ubiquitous
      environmental carcinogenic PAHs are potent inducers of IL-1 alpha and IL-6
      cytokines and, unlike UVB, they downregulate IL-1 beta in human keratinocytes.

PMID- 8156174
TI  - Increased polymorphonuclear leukocyte Fc gamma-dependent chemiluminescence in
      active psoriasis is not related to FcRIII (CD16) receptor expression.
AB  - The role of the two main serum opsonins (IgG and C3b) in the induction of
      polymorphonuclear leukocyte chemiluminescence was studied in a group of psoriatic
      patients. Chemiluminescence was stimulated with zymosan opsonized by fresh plasma
      (IgG- and C3b-dependent chemiluminescence) or by complement-depleted plasma (IgG
      dependent chemiluminescence). While C3b-dependent chemiluminescence was similar
      in patients with chronic or active forms of psoriasis, IgG-dependent
      chemiluminescence was significantly increased in patients with active disease.
      However, FcR-III expression, evaluated by means of flow cytofluorimetry, was
      similar in the different groups of patients studied. The discrepancy between Fc
      receptor (CD16) expression and IgG-dependent chemiluminescence is, therefore,
      indicative of modifications that occur in psoriatic neutrophils that do not
      involve FcIII-receptor expression.

PMID- 8156175
TI  - UVA irradiation stimulates the synthesis of various matrix-metalloproteinases
      (MMPs) in cultured human fibroblasts.
AB  - UVA irradiation leads to photoaging including clinical features such as wrinkle
      formation, reduced recoil capacity and blister formation of the skin. Besides
      synthesis of the extracellular matrix, its regulated degradation by various
      matrix-metalloproteinases (MMPs) determines the amount and the composition of the
      extracellular matrix within the dermis and the basement membrane of the dermo
      epidermal junction. In this study we therefore ascertained whether UV irradiation
      could modulate the synthesis of MMPs with substrate specificities for dermal
      (collagen I, III, V) and basement membrane compounds (collagen IV, VII,
      proteoglycans, laminin) and whether synthesis of the counteracting tissue
      inhibitor of metalloproteinases (TIMP-1) was also affected. Following UVA
      irradiation specific mRNAs of MMPs 1, 2 and 3 were induced concomitantly up to 5
      fold compared to mock irradiated controls. In contrast, TIMP-1 mRNA levels
      remained unaltered. Immunoprecipitation indicated that after UVA irradiation
      synthesis and secretion of MMPs 1, 2 and 3 into the supernatant increased. Taken
      together, our data show that UVA irradiation coordinately induced MMPs 1, 2 and 3
      implying similar mechanisms in their regulatory pathways, while TIMP-1 synthesis
      was not altered. Hence, unbalanced synthesis of MMPs potentially contributes to
      the dissolution of dermal and basement membrane compounds finally leading to
      blister formation and cutaneous photoaging.

PMID- 8156176
TI  - Carotid surgery trials teach the obvious--again.

PMID- 8156177
TI  - Smoking after acute myocardial infarction: a good thing?

PMID- 8156178
TI  - Prevention of disability due to cardiovascular diseases.
AB  - Emotional distress and interpersonal stress are extremely common in patients
      after myocardial infarction and typically lessen over several months. However, it
      is important for physicians to screen patients with CAD for certain conditions
      that may need further assessment and possible treatment by a mental health
      professional. The examination of the patient with CAD involves assessment of
      psychological functioning, including the patient's level of denial, anxiety, and
      depression; the presence of panic anxiety or depressive disorder; and
      neuropsychological functioning, including memory and concentration. Evaluation
      for the presence of persistent or excessive interpersonal strife, marital
      conflict, and sexual dysfunction is also important. Those with symptomatic
      anxiety, depression, or social or sexual dysfunction should be referred to a
      mental health professional who has expertise in working with CAD patients and is
      knowledgeable about a variety of psychosocial and psychopharmacological
      treatments. Patients with CAD who are unable to modify their cardiovascular risk
      factors satisfactorily after guidelines are clearly articulated should be
      referred to a center designed to help patients identify the obstacles to behavior
      change and to facilitate and maintain long-term adherence to these changes.
      Patients with CAD who are physiologically able to work but have marked work
      stress or a marked reluctance to return to work should be evaluated by a mental
      health professional.

PMID- 8156179
TI  - Analysis of precordial movements.
AB  - Thorough analysis of precordial movements in patients with known or suspected
      heart disease provides valuable diagnostic information in most patients and is an
      important, although often overlooked, part of the initial cardiac examination. As
      with all physical diagnostic methods, information obtained by analysis of
      precordial movements must be carefully integrated with the clinical history and
      other physical findings. Further diagnostic studies may be necessary for certain
      patients, but failure to obtain readily available information during the initial
      examination can lead to important mistakes in diagnosis and unnecessary use or
      misinterpretation of more expensive, risky, and uncomfortable diagnostic tests.
      The result can be compromised patient care. It takes dedication, patience, and
      time to develop and maintain excellent skills in cardiac physical diagnosis.
      Failure to use the time-honored diagnostic methods because of a lack of
      understanding of their value or dependence on more complicated diagnostic tests
      shortchanges both the patient and physician. The newer methods of diagnosis
      complement the physical examination and are valuable when thoughtfully used to
      answer specific clinical questions, but the therapeutic effects of human
      interaction and the professional rewards gained from a physician's skillful use
      of the hands, eyes, and mind cannot be replaced by technology-based techniques.

PMID- 8156180
TI  - The renaissance of clinical electrocardiography.
AB  - There is a renaissance occurring in the use of electrocardiography as a
      diagnostic method, and the primary care physician is deeply involved in the new
      surge of interest. Just as "necessity is the mother of invention," the renewed
      interest in electrocardiography is demanded because the proper diagnosis and
      treatment of patients, especially those with cardiac arrhythmias or acute
      myocardial infarctions, depend on an accurate interpretation of the
      electrocardiogram.

PMID- 8156181
TI  - The use of computed tomography in the diagnosis of stroke.

PMID- 8156182
TI  - Carotid endarterectomy in symptomatic patients.

PMID- 8156183
TI  - Obesity and the heart.

PMID- 8156185
TI  - Pathophysiology of edema in congestive heart failure.
AB  - Congestive heart failure is one of the most important causes of peripheral edema
      seen in clinical practice. Edema in congestive heart failure is the result of the
      activation of a series of humoral and neurohumoral mechanisms that promote sodium
      and water reabsorption by the kidneys and expansion of the extracellular fluid.
      These mechanisms, in concert with abnormal Starling forces such as increased
      venous capillary pressure and decreased plasma oncotic pressure, promote fluid
      extravasation and edema formation. The management of edema in congestive heart
      failure is designed to improve cardiac function and to inhibit the hormonal and
      neurohumoral pathways that promote edema. The combination of diuretics and
      vasodilators or angiotensin converting enzyme inhibitors and, in some cases,
      cardiac inotropic agents is highly effective in achieving these goals and
      providing significant symptomatic improvement in patients with edema secondary to
      congestive heart failure.

PMID- 8156184
TI  - Acute arterial occlusion.

PMID- 8156186
TI  - Pulmonary hypertension and chronic cor pulmonale.

PMID- 8156187
TI  - Silent stroke.

PMID- 8156188
TI  - Recognition and management of mitral regurgitation.

PMID- 8156189
TI  - Heart disease and stroke.
AB  - Heart disease is the probable source of emboli in 20% to 25% of cases of cerebral
      infarction. The risk of early death is 14 times greater than the risk of
      recurrent stroke in patients with cardioembolism: Selection of diagnostic tests
      should be based on the clinical evidence for cardiac disease, the patient's age,
      and the identification of other likely causes of stroke. Treatment should focus
      on decreasing mortality due to cardiac disease as well as preventing recurrent
      stroke. Warfarin is currently the first treatment of choice for most patients
      with presumed cardioembolism. Aspirin is an appropriate alternative if warfarin
      cannot be used.

PMID- 8156190
TI  - The future of cardiac surgery.
AB  - Cardiac surgery in the future will probably be different than it is today. It is
      unlikely that the general changes that have occurred in the demands on cardiac
      surgeons and cardiologists and their responses to them will be reversed.
      Therefore, it is likely that the role of the primary care physician in decision
      making will increase. However, constantly upgraded, properly analyzed, and
      properly displayed information about the decreasing risks and increasing benefits
      of cardiac operations needs to be made available to the primary care physician.

PMID- 8156191
TI  - Aspirin benefits many heart and stroke patients but shouldn't be taken by
      everyone.

PMID- 8156192
TI  - Proceedings of the 1992 Society of Quality Assurance Annual Meeting. Atlanta,
      Georgia, September 29-October 2, 1992.

PMID- 8156193
TI  - OECD GLP initiatives and Italian GIQAR.

PMID- 8156194
TI  - A practical approach to assessing PC validation.

PMID- 8156195
TI  - Quality considerations in inhalation toxicology.

PMID- 8156196
TI  - Assuring quality in inhalation exposure research.

PMID- 8156197
TI  - A reviewer's perspective and generic problem areas experienced by registrants
      submitting physical chemistry data under FIFRA and FFDCA.

PMID- 8156198
TI  - The EPA's new chemicals program under TSCA.

PMID- 8156199
TI  - Residue chemistry guidelines.
AB  - Residue chemistry guidelines are designed to determine what the potential
      residues in food are and how much may be present as a result of pesticide
      application, so that a tolerance level may be established. Some requirements are
      established to assist in the enforcement of tolerances by the USDA, FDA, and the
      states. I realize I have given you a quick overview of the residue chemistry
      requirements. There are many documents which are available if you should require
      more information, such as the Subdivision O Residue Chemistry Guidelines,
      Standard Evaluation Procedures (which are used by reviewers when evaluating the
      studies), the Data Reporting Guidelines (which provide guidance on preparing
      final reports), and the Technical Guidance from Phase III of Reregistration. We
      have also released various papers on studies when additional guidance is
      required. Most of these documents are available from NTIS. I hope you will
      consider this information when auditing residue chemistry studies. As I see the
      efforts that you, the QA professionals, have made to educate yourselves on
      residue chemistry studies through programs such as this meeting, I have a little
      more confidence in answering the question "Do you trust them?" with a "Yes."
      Thank you.

PMID- 8156200
TI  - Activities of the Spray Drift Task Force.

PMID- 8156201
TI  - Lysimeter/groundwater monitoring studies.

PMID- 8156202
TI  - The regulation of biopharmaceuticals.

PMID- 8156203
TI  - Certification for research quality assurance professionals in the UK.

PMID- 8156204
TI  - FDA state of affairs.

PMID- 8156205
TI  - Japanese GLP initiatives.

PMID- 8156206
TI  - EPA state of affairs.

PMID- 8156207
TI  - A method for communication and performance assessment among multiple corporate
      quality assurance units: the QAU Monthly Status Report.

PMID- 8156208
TI  - Quality assurance responsibilities as defined by the EPA Good Automated
      Laboratory Practices (GALPs).
AB  - In December 1990, the Environmental Protection Agency's (EPA) Office of
      Information Resources Management (OIRM) issued a draft of the Good Automated
      Laboratory Practices (GALP). The GALPs developed from a union of existing Federal
      and EPA regulations and policies, including: the Federal Insecticide, Fungicide
      and Rodenticide Act (FIFRA) & Toxic Substance Control Act (TSCA), Good Laboratory
      Practices (GLP), the EPA Information Resources Management Policy (IRMP), and the
      Computer Security Act of 1987. The GALPs consolidate the regulations and policies
      to provide a single source of reference, and sever as an extension of the GLP
      standards (40 CFR 160 & 792). Whereas the GLPs describe acceptable laboratory
      management practices, the GALPs describe acceptable automated data management
      practices, and give guidance for standardizing and implementing procedures to
      ensure the quality and integrity of automated data collection and storage. The
      GALPs have been formatted to parallel the structure of the GLPs. Just as the GLPs
      define the responsibilities of the Quality Assurance Unit (QAU) in maintaining
      good laboratory practices, the GALPs define the responsibilities of the QAU in
      maintaining good automated data practices. The QAU is charged with (i)
      maintaining copies of written procedures for the automated data collection
      system, (ii) performing inspections of laboratory operations utilizing the
      automated data collection system and reporting findings, (iii) ensuring
      authorization and documentation of deviations from written procedures, (iv)
      auditing data and reports from the automated data collection system to ensure
      they accurately represent the raw data, and (v) maintaining records of the above
      defined QAU functions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156209
TI  - A new approach to in-house training using CEUs.

PMID- 8156210
TI  - A simple key to EPA's GLP regulation advisories.

PMID- 8156211
TI  - The critical phase inspection process: a benchmarking study in search of
      industries' best practices.
AB  - Benchmarking is the orderly process of measuring one's own products, services,
      and practices against those of companies recognized as leaders. Eli Lilly and
      Company's Quality Assurance Department formed the Critical Phase Inspection Team
      to benchmark the processes for selecting and conducting critical phase
      inspections and reporting inspection findings. The team developed a telephone
      survey that was conducted with 33 other quality assurance units across the
      country. Analysis of the phone survey responses resulted in the identification of
      5 quality assurance units that we felt could provide valuable information to us
      on these activities. Site visits to these companies were arranged and information
      was shared. We present here the analysis and results of our benchmarking
      endeavor. Through the information sharing involved in the benchmarking process,
      namely, the telephone surveys and the site visits, fresh ideas emerged and new
      acquaintances were made. Comparisons and adaptations of our methods with others
      in the quality assurance business will lead us to breakthrough improvements that
      will allow us to improve our current processes.

PMID- 8156212
TI  - Sponsor/contract laboratory communication: a team approach to quality.
AB  - The true measure of any successful quality endeavor is the final product. The
      final product generated at contract facilities conducting nonclinical studies is
      the final report. This should be accurate, complete, and consistent with regard
      to the raw data, and in compliance itself. The final report resulting from
      studies conducted at contract laboratories should be reflective of the
      collaborative efforts of sponsor and laboratory staffs. The dual interaction of
      the respective Quality Assurance Units (QAUs) in ensuring that optimal study
      performance is maintained from initiation through final report submission is of
      paramount importance. Key to any productive sponsor/contract laboratory
      relationship is communication. The multidirectional flow of information inherent
      in the conduct of nonclinical studies must be managed to maximize the strengths
      of the principals involved, while at the same time assuring that consistent
      emphasis is placed on team focus. Although the role of the QAUs representing the
      contract facilities and the sponsor both ensure the quality of study conduct, and
      ultimately the final product, their respective approaches may be from different
      perspectives. The contract QAU's primary focus is the specific study conduct,
      including appropriate inspections of ongoing critical phases and audits of raw
      data and reports, along with compliance to site Standard Operating Procedures
      (SOPs), protocols and sponsor requirements. On the other hand, sponsor QAUs focus
      mainly on overall study conduct, assurance that contract QAUs are operating
      effectively, and ensuring that sponsor monitors are communicating adequately with
      contract facility personnel. Open communication between the respective QAUs is
      the most productive and useful way of ensuring that all quality criteria are
      met.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156213
TI  - Compliance education through participational QA programs.
AB  - Attaining and sustaining an acceptable level of compliance to regulations,
      guidelines, or directives presents a challenge to every company. Compliance
      education programs usually combine in-house tailored programs with extramural
      courses, both of which are very valuable. It is recommended that two motivational
      participational Quality Assurance programs be added to your compliance education:
      (1) Deputy Quality Assurance monitoring program and (2) Quality Assurance group
      auditing. Both programs provide the researcher active involvement, on an ad hoc
      basis, in the compliance assessment process, and an increased awareness of the
      practical application of compliance principles. Through self-discovery and team
      building, both the researcher and Quality Assurance gain a mutual trust and
      respect for their respective expertise. Motivation is enhanced through this
      environment and provides a self-perpetuating impetus for proactive improvements
      in the compliance process. From a Quality Assurance perspective, effective
      compliance education combines in-house tailored compliance programs and
      extramural courses or meetings with these two participational Quality Assurance
      programs. The combination has the potential for going beyond our basic
      understanding of compliance and creating a compliance consciousness that can
      successfully translate into continually improving our compliance programs.

PMID- 8156214
TI  - Quality assurance aspects of an environmental fate study.
AB  - Environmental fate studies pose a challenge to the quality assurance officer due
      to the dynamic nature of the methodology. Protocols must be carefully constructed
      so that the study is conducted within GLP guidelines and is acceptable to the
      agency to which it is to be submitted. These protocols must also be flexible
      enough to adapt to methodologies that might evolve during the study. This
      flexibility requires careful auditing to assure adherence to the protocol and
      methods as they are developed. These ideas will be highlighted in a general
      discussion of the many aspects of environmental fate quality assurance.

PMID- 8156215
TI  - French GLP initiatives and SoFAQ.

PMID- 8156216
TI  - UK GLP initiatives and BARQA and FERQAS.

PMID- 8156218
TI  - Bioequivalence/bioavailability retention samples.

PMID- 8156217
TI  - Overview of field studies.

PMID- 8156219
TI  - CANDA--an introduction, overview, and future visions.

PMID- 8156220
TI  - Training the quality assurance professional.

PMID- 8156221
TI  - Quality assurance auditor training.

PMID- 8156222
TI  - Assuring the integrity, accuracy, and quality of scientific information.

PMID- 8156223
TI  - Good Automated Laboratory Practices.

PMID- 8156224
TI  - A review of fundamentals of EPA's baseline human health risk assessment processes
      and associated QA needs.

PMID- 8156226
TI  - EPA's GLP compliance review of chemistry laboratories.
AB  - The Good Laboratory Practice (GLP) Standards regulations do not provide specific
      requirements for the operation of a specimen analysis laboratory, such as a
      testing facility that performs pesticide residue analysis in support of a
      tolerance study. Thus, some judgment must be applied by a regulated analytical
      laboratory to assure compliance with GLP Standards regulations that were designed
      primarily for testing facilities that apply test substances to test systems. This
      presentation will provide some insight as to EPA's compliance approach, as well
      as identifying problem areas encountered in past inspections of analytical
      laboratories.

PMID- 8156225
TI  - U.S. Food and Drug Administration approach to risk assessment of aflatoxin in
      human foods.

PMID- 8156227
TI  - Inspection of a metabolism study.

PMID- 8156228
TI  - The PC environment--validation of computer systems.

PMID- 8156229
TI  - Good Automated Laboratory Practices and other standards: validation of computer
      systems in the PC environment.
AB  - In summary, the validation of purchased software and add-on programs requires
      careful examination of the situation to determine the most effective and logical
      methods. A standard validation methodology that is used for larger systems would
      be difficult and possibly dangerous to employ for a PC system because of the
      significant differences between the environments. It should be noted, however,
      that there are almost daily changes in the computer software industry. A number
      of potential solutions have emerged over the past few years that can be applied
      to reduce the concerns caused by the apparently insufficient controls in the PC
      environment. For example, currently available technologies would permit multiple
      PC users to access a secure central application or repository of data and prevent
      them from making changes to a validated system or database. A properly designed
      system could enable these distributed users to use the data to perform their
      required functions, while maintaining a validated state.

PMID- 8156230
TI  - Infection in the neutropenic patient: directions for future research.

PMID- 8156231
TI  - A hospital without pain.

PMID- 8156232
TI  - Febrile neutropenia.
AB  - Fever is associated with malignancy and is a common problem in cancer patients.
      Fever in the cancer patients is closely linked with infection, especially when
      the patient is granulocytopenic. When fever appears, a series of diagnostic and
      therapeutic measures must be taken even if precise knowledge of the cause of the
      infection is lacking. Fever can be caused by infection or by the cancer itself
      through tumor-related necrosis, hemorrhage or pyrogens. Infection is the more
      common cause, however. Bacterial and fungal sepsis can coexist and the bacteremia
      can overshadow the more difficult to determine fungal infection. For this reason
      it has become accepted practice to administer amphotericin B to granulocytopenic
      patients who remain febrile after a few days of broad-spectrum antimicrobial
      therapy and in whom no bacteria can be documented. Viral infection is rarely
      diagnosed in neutropenic patients without concomitant immunosuppression.

PMID- 8156233
TI  - Diagnosis and treatment of invasive fungal infections in cancer patients.
AB  - Fungal infections continue to cause major complications in cancer patients. With
      the increasing use of aggressive chemotherapy causing prolonged granulocytopenia,
      and the progress made in the prophylaxis and treatment of bacterial infections,
      the risk of invasive mycoses has increased, particularly in patients with
      hematological malignancies. The prognosis of these infections is poor unless they
      are diagnosed and treated promptly. Early diagnosis, particularly in neutropenic
      cancer patients, is often difficult and antifungal therapy is frequently
      unsuccessful because it is not instituted until the infection is in an advanced,
      fatal phase. In order to reduce the mortality associated with invasive fungal
      infections, antifungal therapy, usually amphotericin B, has been empirically
      carried out in neutropenic patients with fever unresponsive to broad-spectrum
      antibacterial therapy. However, the absence of a marker of the fungal infection,
      the frequent occurrence in these patients of non-infective fever, which does not
      require any antimicrobial therapy, and the possible toxicity of amphotericin B
      represent the major limits of empiric antifungal therapy. In view of the above,
      the study of improved and less toxic antifungal agents, and the evaluation of new
      clinical and laboratory methods for an early diagnosis, have been the major goals
      in research on the opportunistic invasive fungal infections in the last years.

PMID- 8156234
TI  - Cytomegaloviral virus infection in bone marrow transplantation recipients:
      strategies for prevention and treatment.
AB  - Cytomegalovirus is major infectious pathogen following allogeneic bone marrow
      transplantation. In infected recipients, the virus is generally detected between
      4 and 10 weeks after transplantation. Historically, CMV disease developed in 30
      40% of seropositive recipients, the predominante manifestation being interstitial
      pneumonitis, which was generally lethal. Therapeutic interventions are discussed
      with special reference to the use of antiviral therapy for both treatment and
      prevention of CMV disease. The strategies developed in the bone marrow
      transplantation population to treat or prevent the development of CMV disease can
      be extrapolated to other patients groups who are immunosuppressed and at risk for
      developing clinical manifestations of CMV infection.

PMID- 8156235
TI  - Anaerobic bacteremia in a cancer center.
AB  - Seventy-five episodes of clinically relevant anaerobic bacterial bacteremia
      observed in cancer patients were reviewed. Gastrointestinal (22.7%),
      hematological (22.7%) and female genital tract (18.6%) cancers were the most
      common underlying malignant diseases. Among 84 strains of strict anaerobic
      bacteria recovered in the 75 patients, gram-negative rods were isolated in 49
      patients (58.3%), gram-positive rods in 29 patients (34.5%) and gram-positive
      cocci in 6 patients (8%). Bacteroides spp. and Clostridium spp. were the most
      frequent pathogens (85.7%). Twenty-one episodes of bacteremia were polymicrobial,
      aerobic gram-positive cocci being the most frequently associated pathogens. When
      identified, the primary sites were the gastrointestinal tract (40%), the female
      genital tract (17.3%), skin and soft tissue (14.6%), the oropharynx (12%) and the
      lower respiratory tract (6.7%). The source remained unknown in 7 cases (9.3%).
      The overall survival (evaluated 10 days after the occurrence of bacteremia) was
      82.5%. There was no difference in mortality between patients with monomicrobial
      and polymicrobial bacteremia. Pulmonary complications were more frequent in
      patients with fatal outcome in comparison to patients who survived. The mortality
      rate of the patients adequately treated was 10.3% compared to 41% for the
      patients not treated or treated inadequately (P = 0.016, chi 2).

PMID- 8156236
TI  - Pitfalls in the use of opiates in treatment of cancer pain.
AB  - The use of morphine in the treatment of cancer pain is widely accepted among
      people taking care of cancer patients and concerned with pain relief. Several
      problems regarding common side-effects, life-threatening complications in cancer
      and opioid-non-responsive pain syndromes will be discussed. The development of
      grading systems may open new directions for adequate pain control.

PMID- 8156237
TI  - Attitudes of Swiss physicians in prescribing opiates for cancer pain.
AB  - Following clinical observations showing that opiates are sometimes not
      consistently administered for chronic cancer pain, a survey was conducted among
      1200 physicians in the German-speaking part of Switzerland. Their opium
      prescribing habits were assessed by means of a postal questionnaire. The results
      indicate that, among the majority of physicians completing the questionnaire,
      established guidelines and basic principles of pain control with opiates in
      cancer patients are largely understood. Oral morphine is chosen by 89% to
      initiate treatment of chronic cancer pain, and the correct use of slow-release
      morphine is known to 87% of the responding physicians. Unfortunately, an
      important minority of physicians does not follow established guidelines in the
      treatment of cancer pain, and up to 20% still feel that the danger of addiction,
      respiratory depression and other side-effects are important reasons for
      withholding opiates in this patient population. The results and their
      implications are discussed and compared with the current literature on cancer
      pain management.

PMID- 8156238
TI  - Continuity of the doctor/patient relationship during the routine follow-up of a
      breast cancer patient.
AB  - All 551 breast cancer patients diagnosed in 1977-1980 in the Tampere University
      Hospital District (Finland) were followed-up for 5 years. The patients
      experienced a total of 1778 woman years during the first 5 years of follow-up.
      There were more than 20 visits in the first 5 patient years, most to hospitals
      with specialists in surgery or oncology. Patients saw the same doctor twice, on
      average, and met an average of 10 different doctors during the 5-year follow-up.
      The case notes consisted of virtually complete information on the diagnostic
      tests and disease but rather incomplete information on patients' well-being. It
      is concluded that the continuity of the doctor/patient relationship was poor, and
      that consulting the same physician would probably improve the quality of life
      among breast cancer patients.

PMID- 8156239
TI  - "Learning to cope"--an intervention in cancer care.
AB  - As reported, cancer patients and their significant others need information to
      promote their understanding of events throughout the illness, and support to
      mobilize coping strategies when they consider the demands of the situation exceed
      their personal resources. It has, however, repeatedly been reported that
      communication barriers exist and that information does not always reach the
      target. In the present study the provision of information entered the field of
      education. An education and support program was developed, based on results from
      a learning-needs assessment. The program has now been evaluated. Cancer patients
      and their significant others (n = 127) participated in group sessions. After
      completion of the program, open interactive interviews organized around
      experiences of increased knowledge and understanding, and enhanced coping
      capacity related to participation in the program were conducted with the
      participants. The interviews were analyzed using the grounded theory approach.
      The findings indicate that supportive education, sensitively responsive to
      expressed needs and learning capability, has the power to promote proper
      understanding and facilitate coping efforts. Becoming familiar with facts and
      feeling reinforced confidence in evolving appropriate coping strategies for
      living with cancer.

PMID- 8156240
TI  - The influence of supportive nutritional therapy via percutaneous endoscopically
      guided gastrostomy on the quality of life of cancer patients.
AB  - Between April 1987 and May 1990 a total of 212 consecutive patients with tumours
      in the head and neck region were admitted to a prospective study comparing
      planned prospective enteral nutrition via percutaneous endoscopically guided
      gastrostomy (PEG; n = 47) and oral nutrition (n = 134). The nutritional status
      (anthropometric and laboratory chemical parameters) and the quality-of-life index
      according to Padilla et al. [Res Nurs Health 6:117-126 (1983)] were determined
      prior to radiotherapy, 2, 4, 6 weeks later during radiotherapy and 6, 12 and 18
      weeks after completion of radiotherapy. The quality-of-life score of the orally
      nourished patients decreased quickly during radiotherapy and improved only slowly
      afterwards. Although PEG patients had a worse starting score, their quality-of
      life index did not deteriorate during therapy (statistically significant
      difference between the two groups). The same applies to the nutritional status.
      These results show that an early and constant enteral nutrition by PEG can
      stabilize the nutritional state and the quality of life of patients with tumours
      of the head and neck area during radiotherapy.

PMID- 8156241
TI  - Professional rehabilitation of lymphoma patients: a study of psychosocial factors
      associated with return to work.
AB  - During the last ten years a substantial reduction in mortality has been obtained
      for Hodgkin's and non-Hodgkin's lymphoma. Since lymphoma treatment is often
      accompanied by side effects and long-term sequelae, however, patients often have
      problems with rehabilitation. It is thus very important that these problems and
      needs be identified. Going back to work is one of the main objectives of
      rehabilitation and can be taken as a valuable indicator of the problems and needs
      of such patients. We therefore conducted a study at the Jules Bordet Institute
      between December 1989 and December 1990. Of the patients in remission and able to
      go back to work, only 54% of them have done so. Anxiety, depression, and
      treatment toxicity interfere with return to work, and the likelihood of job
      reentry increases with the time lapse since the end of treatment. Rehabilitation
      programs must focus on alleviating illness and treatment sequelae as soon as
      treatment ends.

PMID- 8156242
TI  - Malignant and non-malignant chronic pain: therapy, opioids and fears. Swiss
      Centre for Paraplegia, Nottwil, 6 May 1993.

PMID- 8156243
TI  - Fighting cancer cachexia--what about today's armory?

PMID- 8156244
TI  - Fatigue and cancer: inevitable companions?

PMID- 8156245
TI  - Pathophysiology of cancer cachexia.
AB  - Patients with advanced cancer and cachexia typically demonstrate modestly
      increased rates of energy expenditure in the presence of diminished food intake
      due to anorexia and to gastrointestinal disturbances. Rates of glucose production
      by the liver, gluconeogenesis and glycolysis to lactate (Cori cycle) are
      increased, fat mobilisation and oxidation are accelerated. There is a
      redistribution of body proteins away from muscle towards visceral proteins,
      resulting in marked muscle protein loss. Cancer cachexia differs from simple
      starvation and demonstrates metabolic similarities to sepsis or polytrauma. The
      metabolic response in the patient with cancer is largely due to mediators
      released by the tumour or by the host; recently the role of cytokines such as
      tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1) and -6 (IL-6) and
      interferon gamma (INF gamma) has been emphasized. Catabolic hormones such as
      glucocorticoids and adrenaline have also been implicated. Cytokines have the
      potential to reproduce experimentally the clinical syndrome of cancer cachexia.
      There is evidence of increased production of several of them in certain types of
      cancer. There are overlapping activities of the cytokines TNF alpha, IL-1, IFN
      gamma and IL-6. The contribution of each of them to cancer cachexia remains
      unclear. Inhibition of cytokine activity using specific antibodies in cancer
      bearing experimental animals demonstrated partial prevention of cachexia. A
      positive feedback between macrophage-derived IL-1 and tumour-derived IL-6 has
      been demonstrated recently in experimental cancer cachexia. Cytokines may support
      tumour growth by acting as growth factors.

PMID- 8156246
TI  - Critical reappraisal of vitamins and trace minerals in nutritional support of
      cancer patients.
AB  - The potential of a high intake of fresh fruits and vegetables in cancer
      prevention is well established. Epidemiological studies support carotene,
      vitamins A, C, E and selenium as the active compounds. Antioxidant properties and
      direct effects (e.g. inhibition of N-nitrosamine formation or cell-to-cell
      interactions) are invoked. The role of other trace elements is less clear. The
      modulation of immune function by vitamins and trace elements remains important
      and affects survival. In established cancers, the site-specific differences in
      the diet/cancer relation require appropriate dietary changes, e.g. low fat (20%
      by energy) in breast cancer, or high vegetable or fruit intake in lung cancer.
      Single high-dose supplements (e.g. vitamin C) have proved to have no curative or
      life-prolonging effect. Chemotherapy and radiation increase the requirements for
      antioxidant compounds. Supplementation can diminish the damage induced by
      peroxidation. Carefully planned and monitored trials that establish the optimal
      intake of micronutrients as adjuvants in cancer patients are required.

PMID- 8156247
TI  - Is the pharmacological treatment of cancer cachexia possible?
AB  - Cancer cachexia is highly prevalent in patients with advanced cancer. Its main
      clinical manifestation is profound anorexia. Progestational drugs have shown
      meaningful effects on appetite, food intake, and nutritional status in patients
      with advanced cancer and AIDS, and could be useful in managing anorexia.
      Corticosteroids also seem to produce increased appetite, but these effects are
      short-lived. Cyproheptadine, hydrazine sulfate, and cannabinoids also are being
      studied in the management of cancer-induced anorexia, but their role has not yet
      been clearly established. Future research should evaluate how the different drugs
      affect specific symptoms associated with cachexia.

PMID- 8156248
TI  - Assessment of fatigue in cancer and non-cancer patients and in healthy
      individuals.
AB  - Fatigue is a very complex phenomenon. It has been described as a major
      distressing symptom in cancer patients. It is a multidimensional experience that
      focuses not only on biochemical or pathophysiological causes, but also involves
      psychological and behavioural aspects. Until today, measurement of fatigue has
      been a neglected topic in medicine and nursing and a nihilistic attitude still
      prevails. The lack of valid, reliable tools of measurement is one of the problems
      inhibiting further research. Only recently has quality-of-life research begun to
      acknowledge this phenomenon and include fatigue in assessment. In this study,
      fatigue was measured and explored in cancer patients non-cancer patients and in
      healthy individuals. A clear distinction evolved between "healthy" fatigue in
      healthy individuals and "unhealthy" fatigue in cancer patients, where the impact
      of fatigue was far more negative. Characteristic fatigue profiles underlined
      these findings. The new visual-analogue fatigue scale, to measure fatigue four
      times daily, proved to be very useful. Further research is needed to develop
      therapeutic strategies and to support the patients who have to cope with this
      distressing symptom.

PMID- 8156249
TI  - "Fatigue and malaise" as a quality-of-life indicator in small-cell lung cancer
      patients. The Swiss Group for Clinical Cancer Research (SAKK)
AB  - "Fatigue and malaise" (FM) is a frequent, non-specific symptom of cancer patients
      caused by the disease, its treatment and psychological distress. Since
      comprehensive quality of life assessment is often not feasible in multicentre
      clinical trials, short, but clinically relevant, quality of life indicators have
      to be defined. In a representative subsample of 127 patients in a phase-III
      randomized small-cell lung cancer trial comparing two different regimens of
      combination chemotherapy, quality of life was assessed at the beginning of each
      of the six treatment cycles with a self-rating questionnaire including an early
      version of the EORTC questionnaire, a mood adjective check list (Bf-S) and a
      single linear-analogue self-assessment scale (LASA) measuring general well-being.
      FM, measured with a five-item Likert subscale of the EORTC questionnaire, showed
      moderate to high intercorrelations with other EORTC subscales assessing disease
      symptoms, toxicity of treatment, role functioning, personal functioning,
      restriction of social activity, psychological distress, emotional (Bf-S) and
      general well-being (LASA). At baseline, FM was one of the most pronounced
      symptoms. Over the six cycles 43%-31% of the patients complained of moderate to
      severe fatigue. Over the first two cycles FM tended to decrease, slightly
      increasing during cycles 3 and 4 and decreasing again before cycle 6. In a
      multiple regression analysis over the six cycles, 53% of the variance of FM was
      explained by patient-rated symptoms of disease and toxicity (disease alone: 43%;
      toxicity alone: 35%). Initial performance status, previous weight loss, treatment
      arm, cycle number and age predicted the scores of FM over the six
      cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156250
TI  - Fatigue affecting family caregivers of cancer patients.
AB  - Fatigue, a universally reported symptom, may be one of the most prevalent
      feelings of people suffering from physical or mental diseases. An understanding
      of the factors leading to fatigue in the caregiving population can contribute to
      better care and support of both the cancer patient and the caregiver. The purpose
      of this discussion is to investigate and describe the experience of fatigue among
      caregivers of cancer patients in relation to caregiver age, employment status,
      number of hours of care provided daily, duration of caregiving, and the impact
      upon the caregiver's schedule. A sample of 248 caregivers of cancer patients,
      participating in the Family Homecare Cancer Study, were surveyed regarding
      fatigue related to their caregiving roles. No relationship was found between
      severity of fatigue experienced by the caregiver of the cancer patient and
      caregiver age, employment status, the number of hours of daily caregiving, or its
      duration. However, a significant relationship was found between fatigue and the
      impact of care on the daily schedule. This finding has strong implications for
      the health-care provider, because the more the caregiver's schedule is a burden,
      the greater will be the fatigue experienced.

PMID- 8156251
TI  - Food avoidance in patients undergoing cancer chemotherapy.
AB  - Cancer and its treatment are known to cause malnutrition in significant numbers
      of patients. Although a variety of contributory factors have been identified it
      is clear that the aetiology of malnutrition is complex and multifactorial. Taste
      aberrations are believed to be amongst the causative factors and to contribute to
      the development of food avoidance/aversion in affected patients. The study
      described investigates the incidence of food avoidance in a random sample of 72
      patients undergoing cancer chemotherapy. The results show that 59 (82%) had
      avoided one or more foods since the instigation of treatment. The foods most
      commonly affected were coffee, tea, citrus fruit, chocolate and red meat. Changes
      were noted in the consumption of both sweet and salty foods. In terms of food
      avoidance no apparent relationships were demonstrated between its incidence and
      either the type of disease or the drugs used in therapy. In men, the pattern of
      avoidance showed no differences between the younger (up to 49 years) and older
      (50 years and older) patients; marked differences were observed between younger
      and older women. Although the foods avoided in general have little nutritional
      implication their omission may affect the quality of the patient's life. Food
      avoidance per se may, however, affect nutritional status; suggestions for
      overcoming its effects are made. The results of this study, obtained by
      subjective assessment of food acceptability, highlight the individual nature of
      food avoidance in affected patients and suggest that each must be individually
      assessed if appropriate nutritional advice is to be given.

PMID- 8156253
TI  - PANG (Pain and Nociception Group) London Chronic Pain Symposium, 10-12 May 1993.

PMID- 8156252
TI  - Respiratory distress syndrome in patients with advanced cancer treated with
      pentoxifylline: a randomized study.
AB  - The inappropriate endogenous secretion of tumour necrosis factor (TNF) could play
      a role in the pathogenesis of acute respiratory distress syndrome (ARDS), one of
      the most frequent causes of death in cancer patients. Because of its capacity to
      inhibit TNF secretion in vitro, pentoxifylline (PTX) could be extremely useful in
      ARDS therapy. In this study 30 advanced cancer patients with ARDS were randomized
      to receive either the conventional care or conventional care plus PTX (100 mg
      i.v. twice a day for 7 days followed by an oral administration of 400 mg three
      times a day) to evaluate the efficacy of PTX in reducing TNF serum levels and in
      improving the symptoms of this syndrome. Serum levels of TNF were measured before
      and after 7 days of therapy. The percentage of patients alive at 7 days was
      significantly higher in the PTX-treated group than in the controls (12/15 versus
      3/15; P < 0.001). The mean survival time was significantly higher in the PTX
      treated group than in the controls. A clinical and/or radiological improvement
      was obtained in 11/15 patients treated with PTX and in only 2/15 patients in the
      conventional care group (P < 0.01). TNF mean levels significantly decrease in the
      PTX-treated group. These data confirm in vivo the capacity of PTX to inhibit TNF
      secretion in patients with ARDS. Moreover PTX therapy may improve the symptoms
      related to ARDS without particular toxic effects.

PMID- 8156254
TI  - To care is good, to educate is better.

PMID- 8156255
TI  - Bone marrow transplantation today.
AB  - Today, bone marrow transplantation (BMT) is an established therapy. This
      statement is best verified by the number of BMTs performed. Between January 1990
      and December 1992, 172 European teams in 26 countries carried out a total of
      14,334 transplants. There were 6642 allogeneic transplants: 5513 BMT from an HLA
      identical sibling donor, 370 from a non-identical family member, 88 from an
      identical twin donor and 671 from an unrelated volunteer donor. There were 7692
      autologous transplants: 6577 autologous bone marrow, 777 peripheral-blood stem
      cell and 338 combined bone-marrow and peripheral-blood stem-cell transplants.
      Indications were: leukaemias in 52% (7479), lymphoproliferative disorders in 29%
      (4125), solid tumours in 11% (1540), aplastic anaemia and thalassaemia in 3%
      (487) and inborn errors an miscellaneous disorders in the remaining 5% (703). The
      results of these transplants are not yet known. From previous analyses it can be
      expected that more than 50% of patients will be alive and well 10 years after
      BMT. The main factors influencing outcome are known; they depend on type, sub
      type, stage of disease at time of transplant, the time from diagnosis to
      transplant and the conditioning regimen for all transplants. For allogeneic BMT,
      donor source, donor and recipient age, sex, donor/recipient sex combination,
      donor and recipient viral status, graft-versus-host disease prevention method and
      region are additional factors. Knowledge of these factors enables us today to
      estimate the potential risk and adjust the therapy for an individual patient.

PMID- 8156257
TI  - Instruction in the techniques and concept of supportive care in oncology.
AB  - Cancer education merits a coordinated, vertical curriculum and an integrated
      planning strategy. It has become clear that it is as important to teach the
      techniques of supportive care in oncology as it is to teach the concepts of
      cancer biology, pathology, epidemiology, prevention, detection and aggressive
      treatments. Our aim is to determine whether the medical school and nursing school
      curricula give the students an introduction to the concepts of supportive care of
      the cancer patient. The spectrum of such supportive care encompasses a wide range
      of issues working towards a common goal of providing overall comfort with an
      emphasis on quality of life, and runs parallel with specific therapeutic
      strategies and associated problems. Do the graduate medical student and nursing
      student understand that cancer management is multidisciplinary and team-based?
      That the approach to pain management not only includes the administration of pain
      medications, but should also evaluate pain assessment and anesthetic,
      neurosurgical and behavioral approaches? That nausea and vomiting associated with
      chemotherapy can be ameliorated to a certain extent? That infections are common
      but algorithms exist for prevention and therapy? That certain metabolic
      complications are unique to cancer patients? That transfusions are vital
      procedures in patients with neoplasms undergoing aggressive treatments but are
      associated with certain risks and complications? That there are serious
      psychosocial, ethical and legal needs to be considered? To address these issues,
      the American Cancer Society Professors of Clinical Oncology, the American Cancer
      Society Professors of Oncology Nursing and the United States Cancer Center
      Directors were surveyed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156256
TI  - Bone marrow transplantation: support of the patient and his/her family.
AB  - Bone marrow transplantation (BMT) has evolved over the last decade from a
      controversial research procedure to a standard therapeutic modality, becoming an
      important innovative treatment for hematological malignancies, solid tumors,
      immunodeficiency diseases and metabolic disorders. Historically in research and
      clinical literature, the BMT procedure is divided into several stages, each
      accompanied by particular emotional tones and psychological issues. In providing
      care for transplant recipients, donors, and families, caregivers must be familiar
      with the psychological stages of the procedure, the psychological themes such as
      body image, and the patient's mechanisms of coping with the stress of such
      protocols. BMT's complex regimens of high-dose chemotherapy and total-body
      irradiation, germ-free environments, graft-versus-host disease, and total
      parenteral nutrition can precipitate significant psychological sequelae in some
      patients with acute and long-term consequences. In response to their illness,
      transplant patients may also develop emotional disturbances of anxiety,
      depression, agitation, and non-compliance. This paper will address the
      psychological care of the patient, donor and family from pre-BMT consultation,
      through informed consent, hospitalization and convalescence. Various
      psychotherapeutic, pharmacological and behavioral interventions will be briefly
      described. Finally, areas of research in quality of life after BMT and factors
      that may predict BMT adjustment and outcome will be explored. We hope this brief
      paper will familiarize the reader with this psychologically intriguing field and
      will provide a departure point for future reading, study, research, and
      patient/family care.

PMID- 8156258
TI  - Support of the transplant team.
AB  - Both patients and staff in a bone marrow transplantation (BMT) unit have to cope
      with the effects of an aggressive treatment that helps many patients but also
      kills some. This has led to the regular involvement of support services in most
      American BMT units. This article describes the experience in 4 years of
      continuous psychosomatic liaison activity at the BMT unit at the University
      Hospital in Basel. The specific stressors a transplant team is subject to are
      described, such as high morbidity and mortality of patients and the close
      relationship between patients and staff members. Support for the transplant team
      consists in the following activities: a psychosocial interview with each patient
      at the beginning of his or her hospital stay; weekly psychosocial round-ups with
      the whole team; regular participation in ward rounds; organization of workshops
      to prevent burnout. Although an empirical evaluation of this approach is lacking,
      the clinical evidence suggests that constant and reliable team support helps to
      stabilize the team, adding to its inner security. This ultimately improves
      patient care.

PMID- 8156259
TI  - Pamidronate for pain control in patients with malignant osteolytic bone disease:
      a prospective dose-effect study.
AB  - In a prospective dose-escalation study tolerability and effectiveness of repeated
      infusions with intravenous pamidronate were investigated. A total of 80 patients
      with proven malignancy and pain due to osteolytic bone disease were enrolled.
      Doses of 30 mg, 45 mg, 60 mg and 90 mg pamidronate, given every 4 weeks, 3 weeks
      or 2 weeks were tested. Thus dose intensity was increased by giving higher doses
      and/or by shortening the intervals. A combined palliation score on the bases of
      pain score (WHO), analgesic score (WHO) and improvement of performance status
      (SAKK/ECOG) was rated by the physician on a six-point scale. Regression analysis
      showed a close correlation between dose intensity and effect (Pearson's R = 0.7:
      P < 0.0001). A statistically significant different palliative score for patients
      treated with low (below 15 mg/week), medium (16-30 mg/week) and high doses (above
      31 mg/week) of pamidronate was found (P = < 0.01). A dose intensity below 10 mg
      pamidronate/week and single doses of 30 mg had no clinically relevant benefit,
      whereas dose intensities of 25-45 mg/week showed a significant palliative effect.
      We conclude that pamidronate should be given in a close intensity of 20 mg per
      week or more in patients with far advanced osteolytic bone disease. Best results
      are obtained with high doses of 60 mg or 90 mg pamidronate. Further
      investigations by prospective randomized trials are needed to determine the
      optimal dose and schedule of pamidronate infusions.

PMID- 8156260
TI  - Results of antibiotic treatment of Hickman-catheter-related infections in
      oncological patients.
AB  - A group of 330 oncological patients were supported throughout a 7-year period
      with central venous catheters (Broviac/Hickman catheters) and underwent standard
      oncological chemotherapy, because of hematological malignancies or solid tumors
      (156 children), or a myeloablative conditioning regimen followed by bone marrow
      transplantation because of leukemia or lymphoma (174 patients: 110 adults, 64
      children). Of these, 17 patients (8 after bone marrow transplantation) developed
      a catheter-related bacteremia and were treated by at least two antibiotics
      according to the sensitivity of the bacteria. In 1 patient the catheter (infected
      by Bacillus cereus) was removed on day 25 of antibiotic treatment because of
      persistent high fever and further positive blood cultures. After bone marrow
      transplantation, 2 other patients, with a Pseudomonas or a Staphylococcus
      infection respectively, did not respond to the combined antibiotic treatment and
      died 1 week and 7 weeks later, respectively, from transplant-related severe graft
      versus-host disease. In the other 14 patients antibiotic treatment was successful
      and removal of the central-vein catheter could be avoided.

PMID- 8156261
TI  - A pilot study to assess the efficacy of salmon calcitonin in the relief of
      neuropathic pain caused by extraskeletal metastases.
AB  - Although the pain-relieving activity of salmon calcitonin has been mainly
      demonstrated for painful bone metastases it has been postulated that the drug
      possesses a central analgesic activity which is independent of the opiate
      receptor system. Thus, 16 patients with neuropathic cancer pain due to radicular
      compression by extraskeletal metastases, and without the possibility of any
      specific anticancer treatment, entered the study. Of the 16, 11 were pretreated
      with opiate-type analgesics. Salmon calcitonin was applied once daily at a dose
      of 200 IU in 500 ml 0.9% NaCl infused over 1 h. The total duration of the
      treatment was 20 days. The pain-relieving effect was classified as very good,
      good, moderate and bad; in 10 patients it was described as bad, in 2 as moderate
      in 2 as good and in 2 as very good. The drug failed in 9/11 opiate-pretreated
      patients. It is suggested that salmon calcitonin pain-relieving activity might
      depend on the tumor type, previous pain-relieving drug intake and site of
      metastatic disease.

PMID- 8156262
TI  - Trends in Invasive Fungal Infections II, 2-4 September 1993, Manchester, UK.

PMID- 8156263
TI  - Assessment of cancer pain: a continuous challenge.
AB  - A comprehensive assessment of cancer pain is the first and perhaps most important
      step toward pain relief. Yet, this assessment is frequently neglected in patients
      with cancer pain. This paper addresses five important aspects of cancer pain
      assessment: (1) What constitutes cancer pain assessment? (2) Why is it important?
      (3) Why is it frequently overlooked? (4) How can a cancer pain assessment program
      be implemented? (5) What changes can be expected as a result of routine cancer
      pain assessments? The fundamental assumptions underlying this discussion are that
      health-care providers must understand the intensity of their patients' pain and
      the likely etiology of that discomfort to direct an appropriate diagnostic
      evaluation and to initiate and evaluate the success of therapy. Instituting a
      routine pain assessment program need not be difficult. The recommended procedures
      must be simple, quantifiable, relevant, and recorded in the medical record.
      Routine pain assessment will promote a heightened sense of awareness and
      responsibility about cancer pain issues in health-care providers, improved
      communication between the patient and the health-care provider, the development
      of cancer pain quality-assurance programs, and improved care for patients with
      cancer and pain.

PMID- 8156264
TI  - Advances in behavioral intervention in comprehensive cancer treatment.
AB  - This discussion reviews the current status of behavioral intervention with adult
      and pediatric cancer patients. The goal is to give the front-line clinician a
      basis for determining which behavioral intervention procedure to incorporate into
      clinical practice. After defining the term behavioral medicine and describing its
      new role in comprehensive cancer treatment, the discussion examines the use of
      behavioral procedures to control aversive side-effects of treatment. Although the
      control of chemotherapy side-effects is the primary focus (since most of the
      behavioral research on symptom control has dealt with reduction of nausea and
      vomiting with chemotherapy), the application of behavioral principles to other
      side-effects (i.e., anxiety and pain) associated with the aggressive treatment of
      cancer is assessed. The third topic is behavioral intervention to control child
      distress during invasive procedures. The discussion ends with a consideration of
      new directions of research and practice.

PMID- 8156265
TI  - Salmonella infections in a cancer center.
AB  - Data concerning 40 patients hospitalized in a cancer center and Salmonella
      infection were analyzed. Hematological malignancy was present in 24 patients
      (60%) and solid tumor in 14 patients (35%). Among the predisposing factors,
      antineoplastic chemotherapy was the most frequent (60%) followed by antacid use
      (47.5%), corticosteroids (37.5%), granulocytopenia below 500
      neutrophils/microliters (15%), surgery (10%) and splenectomy (2.5%). Bacteremia
      was the most frequent clinical syndrome accounting for 42.5% of the patients.
      Focal infection, enteritis and carrier state accounted for the remaining 30%, 20%
      and 7.5% respectively. Salmonella typhimurium and S. dublin represented 65% of
      the isolates, with clear association between serotype dublin and bacteremia. All
      S. dublin isolates were resistant to chloramphenicol. Among dublin and
      typhimurium serotypes, 20% the isolates were resistant to the traditional
      antibiotics used in salmonellosis (ampicillin, chloramphenicol, cotrimoxazole).
      All strains were susceptible in vitro to cephalosporins. The frequency of relapse
      was 15% and the overall mortality (within 30 days) attributed to Salmonella
      infection was 15%.

PMID- 8156266
TI  - Transdermal fentanyl in uncontrolled cancer pain: titration on a day-to-day basis
      as a procedure for safe and effective dose finding--a pilot study in 20 patients.
AB  - All communications on the use of transdermal fentanyl as well as the
      recommendations of the manufacturer include the direction that patients should be
      titrated with a short-acting narcotic to control their cancer pain before they
      are converted to a fentanyl transdermal therapeutic system (TTS). We investigated
      the possibility of avoiding this titration phase by immediate fentanyl TTS
      therapy in patients with uncontrolled cancer pain. Dose finding was performed by
      direct titration of fentanyl TTS according to clinical necessity on a day-to-day
      basis. Morphine solution for rescue medication was available. Short-term follow
      up was 28 days, and 20 patients (10 in- and 10 outpatients) were evaluable. On
      the average, sufficient pain control [visual analogue scale (VAS) < 35 mm] was
      reached within 48 h of the start of fentanyl TTS. The mean VAS values before and
      during fentanyl TTS therapy were 53 mm (before), 27 mm (week 1), 21 mm (week 2),
      18 mm (week 3) and 21 mm (week 4). There were statistically significant lower VAS
      values at all follow-up times compared to pretreatment values (e.g. pretreatment
      to day 1: P = 0.019; pretreatment to day 28: P = 0.002; Wilcoxon sign-rank test).
      The mean fentanyl TTS doses were 70 micrograms/h (week 1), 98 micrograms/h (week
      2), 107 micrograms/h (week 3) and 116 micrograms/h (week 4). The differences of
      mean fentanyl TTS does were significantly different between days 1 and 7 (P <
      0.001) and between days 8 and 14 (P = 0.006), but not between days 15 and 21 and
      days 22 and 28.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156267
TI  - Use of acute peritoneal dialysis catheters for intraperitoneal chemotherapy
      instead of the semipermanent/permanent Tenkhoff catheters.
AB  - Intraperitoneal chemotherapy was administered to 13 patients with peritoneal
      carcinomatosis, using acute peritoneal dialysis catheters immediately before the
      administration of the chemotherapy. A total of 59 cycles were administered, with
      insertion of the corresponding catheter. There were no inflow or outflow problems
      and no insertion-related complications. With the removal of the catheter after
      its use, there is no risk of abdominal infections.

PMID- 8156268
TI  - What goes on in Paris when its citizens are on summer vacation?

PMID- 8156269
TI  - Psycho-oncology V: Psychosocial factors in cancer risk and survival. Memorial
      Sloan Kettering Cancer center, New York City, New York, 2-4 October 1993.

PMID- 8156270
TI  - Rehydration or dehydration?
AB  - The ability of medicine to prolong human life through the use of sophisticated
      technology has raised many ethical questions, notably those related to the issue
      of withholding or withdrawing nutrition and hydration from certain patients.
      Health care professionals have begun debating what criteria should be applied
      when treating patients who are not able to choose for themselves. This review
      focuses on some of the dilemmas inherent in this issue.

PMID- 8156271
TI  - Breaking bad news: realistic versus unrealistic hopes.
AB  - Hope is an essential aspect of the therapeutic relationship between cancer
      patients and their carers. Realistic hopes provide considerable support, whereas
      unrealistic hopes can be destructive by impairing the ability to make appropriate
      decisions about future plans, treatment, and issues of personal importance.
      Realistic hopes exist for cancer patients at all stages of their illness.
      Provision of realistic hope facilities the process of breaking bad news. In this
      article, the role of hope is explored. Appropriate hopes are identified from the
      time of pre-diagnostic work-up throughout the phase of definitive treatment and
      into the transition to palliative and supportive care. A practical approach is
      developed, which emphasises communication and listening skills, the importance of
      providing time and the benefits of intermediate goals that facilitate a gradual
      adjustment in hopes as the disease progresses.

PMID- 8156272
TI  - Infections in cancer patients: some controversial issues.
AB  - Despite more than two decades of clinical research into the management of
      infections in the neutropenic cancer patient, many patients still develop serious
      morbidity from infection and all too many still die. A number of controversies
      surround (a) the use of combination versus monotherapy for initial empiric
      administration; (b) the use of vancomycin as part of the initial regimen; (c) the
      origin of Staphylococcus epidermidis infections (i.e., mostly from vascular
      catheters or mostly from the alimentary canal); (d) the use of acyclovir for
      herpes simplex prophylaxis during remission induction for acute leukemia patients
      not undergoing bone marrow transplantation; (e) the use of alimentary canal
      microbial suppression or reverse isolation in a room with laminar air flow, or
      both, as infection prevention techniques. Current recommendations and
      observations include the following. (a) Monotherapy with ceftazidime or imipenem
      is effective and appropriate for patients with moderate granulocytopenia at
      limited risk for infection with a resistant organism. Combination therapy is
      recommended for patients with profound, persistent granulocytopenia who are at
      high risk for gram-negative bacteremia; such bacteremic patients have a better
      prognosis with combined-modality therapy. (b) Vancomycin need not be included in
      the initial regimen although some centers may choose to do so because of the high
      prevalence of gram-positive bacteremias. (c) Despite the ubiquitous presence of
      indwelling vascular catheters, most S. epidermidis infections among neutropenic
      patients originate from along the alimentary canal. (d) Herpes simplex infection
      is much more common following standard remission induction chemotherapy than
      previously recognized. Acyclovir will reduce these infections and concurrently
      probably reduce the likelihood of resultant bacterial/fungal co-infections and
      superinfections. (e) Selective microbial suppression is appropriate for patients
      expected to experience prolonged (more than 2 weeks) or profound (below 100
      granulocytes/microliters) granulocytopenia. Agents chosen should suppress aerobic
      but not anaerobic flora (maintain colonization resistance) and need to have an
      effect on both the oral cavity and esophagus as well as the intestines.

PMID- 8156273
TI  - Structural basis of endotoxin recognition by natural polypeptides.

PMID- 8156274
TI  - The evolution of virulence.
AB  - Why is there variation in the virulence of infectious diseases? Virulence can
      have substantial effects on the genetic contribution of both host and pathogen to
      future generations. Understanding it therefore requires explanation not only in
      terms of cellular and molecular mechanisms, but also in evolutionary terms: what
      is the nature of the selection acting on genes responsible for virulence?

PMID- 8156275
TI  - Short-sighted evolution and the virulence of pathogenic microorganisms.
AB  - For some microorganisms, virulence may be an inadvertent consequence of mutation
      and selection in the parasite population, occurring within a host during the
      course of an infection. This type of virulence is short-sighted, in that it
      engenders no advantage to the pathogen beyond the afflicted host. Bacterial
      meningitis, poliomyelitis and AIDS are three candidates for this model of the
      evolution of virulence.

PMID- 8156276
TI  - Stress responses to viral infection.
AB  - Virus infection leads to an increased production of stress proteins in the host.
      These appear to have two important roles: (1) facilitation of virus replication
      and assembly and (2) recognition by the immune system when expressed on virus
      infected cells and consequent elimination of the infected cells.

PMID- 8156277
TI  - Repeated and persistent infection with Chlamydia and the development of chronic
      inflammation and disease.
AB  - Chlamydia trachomatis is an important human pathogen that mediates disease
      processes capable of inflicting permanent damage. Aggressive inflammatory
      responses to repeated infections, and to a persistent form of this intracellular
      bacterium, are thought to initiate the pathogenic events that lead to the
      debilitating sequelae of blinding trachoma and infertility.

PMID- 8156279
TI  - The localization of osteoarthritis.

PMID- 8156278
TI  - Molecular mimicry and Chlamydia trachomatis infection of eukaryotic cells.
AB  - A new experimental model for microbe-host-cell interaction is proposed in which a
      molecular mimic of heparan sulfate is used by Chlamydia to attach to the
      mammalian cell surface. A heparan-sulfate-like ligand, bound to the surface of
      Chlamydia, mediates infectivity by bridging the microorganism and mammalian cell
      receptors.

PMID- 8156280
TI  - Attitudes of medical students to disabled people.

PMID- 8156281
TI  - Role of central catecholamines in the modulation of corticotrophin-releasing
      factor mRNA during adjuvant-induced arthritis in the rat.
AB  - The development of adjuvant-induced arthritis in the rat is associated with an
      activation of the hypothalamo-pituitary-adrenal axis. In the Piebald-Viral-Glaxo
      strain of rat there is however a paradoxical decrease in corticotrophin-releasing
      factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and a
      decrease in CRF-41 peptide release into the hypophysial portal blood with
      increasing severity of disease. In the present study we have investigated the
      role of endogenous catecholamines within the PVN as possible inhibitory factors
      acting on CRF neurons during adjuvant-induced arthritis. Noradrenaline (NA)
      concentrations were approximately doubled in the PVN of arthritic animals.
      Depletion of endogenous catecholamines following direct 6-OHDA lesions of the PVN
      resulted in a significant depletion in PVN NA. The increase in NA observed in
      arthritic animals appears to have a protective role since depletion of NA
      increased the severity of the disease. Neither the increase in circulating levels
      of corticosterone nor the decrease in CRF mRNA in the PVN were prevented
      following NA depletion. Our results suggest that modification of central
      neurotransmitter systems are able to influence the severity of adjuvant-induced
      arthritis.

PMID- 8156282
TI  - A longitudinal study of peripheral blood mononuclear cell proliferative responses
      to bacterial antigens in reactive arthritis.
AB  - Reactive arthritis (ReA) is a sterile inflammatory arthritis which usually occurs
      after an enteric or genitourinary infection. In recent years it has been
      recognized that synovial fluid mononuclear cells from an affected joint
      demonstrate marked proliferative responses if incubated with preparations of the
      organism triggering the arthritis; peripheral blood mononuclear cell (PBMC)
      responses are typically much smaller. One interpretation of this finding is that
      recognition of the triggering organism is enhanced within the joint compared to
      peripheral blood, but it could also be argued that the PBMC responses are
      actually depressed during acute arthritis. We have examined this possibility in a
      longitudinal study of PBMC proliferative responses in patients with ReA. In this
      study we have demonstrated that PBMC proliferative responses to the triggering
      organism were indeed depressed during acute ReA, and showed a significant
      increase after recovery from the arthritis. These findings also applied to PBMC
      recognition of the recall antigen PPD, and to the response to IL-2.

PMID- 8156283
TI  - Effects of cytokines on alkaline phosphatase and osteocalcin production,
      calcification and calcium release by human osteoblastic cells.
AB  - We examined the effect of TNF-alpha, IL-1 beta and IL-6 on alkaline phosphatase
      (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in
      human osteoblastic cell cultures obtained from human periosteum. The cells were
      cultured with varying concentrations of cytokines for 3 days. TNF-alpha and IL-1
      beta significantly inhibited ALP production, decreased cellular Ca content, and
      significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the
      other hand, significantly suppressed 45Ca release by osteoblastic cells. These
      cytokines did not influence the production of OC by osteoblastic cells. The
      results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation
      and calcification and that the effects of IL-6 on osteoblastic cells may be
      different from those of TNF-alpha or IL-1 beta. These effects on osteoblastic
      cells may be one of the mechanisms by which bone loss occurs in patients with RA.

PMID- 8156284
TI  - Reduced activity of serum creatine kinase in rheumatoid arthritis: a phenomenon
      linked to the inflammatory response.
AB  - In a case-controlled study, serum creatinine kinase (CK) activity was
      significantly lower in 40 patients with RA than in 40 age- and sex-matched
      patients with non-inflammatory arthropathies [mean 37.6 (S.D. 29.2) vs 77.7 (S.D.
      45.3) IU/l respectively P < 0.0001]. In contrast, serum levels of aldolase and
      myosin were not significantly lower in RA patients. A significant inverse
      correlation between CK activity and ESR, CRP and platelet count was observed in
      RA. There was also a positive correlation between haemoglobin levels and CK
      values. No correlation was found between CK activity and a meager mass index,
      disease duration and radiological erosion. No inhibitor of CK activity in the
      sera of RA patients was found. CK serum activity was markedly reduced in RA, and
      is related to the inflammatory activity of the disease. This finding may
      stimulate further exploration on the effect of inflammatory response in muscle
      metabolism.

PMID- 8156285
TI  - Bioavailability of hydroxychloroquine tablets in patients with rheumatoid
      arthritis.
AB  - Nine patients with RA received two doses of 155 mg racemic hydroxychloroquine
      each, as a tablet and by i.v. infusion, in a randomized cross-over design study.
      Blood concentrations over the first 32 h following each dose were determined.
      Bioavailability was estimated using a sequential exponential least squares
      deconvolution method. The mean fraction absorbed from the tablet was 0.79 (range
      0.39 to 1.27). The mean absorption lag-time was 1.3 h (range 0.5 to 3.7 h) and
      the mean time for 50% absorption was 4.3 h (range 1.9 to 10.3 h). Mean rate and
      extent of hydroxychloroquine absorption were not significantly different from
      that previously reported for healthy volunteers, although the interindividual
      variability in absorption parameters was greater in the patient group.
      Variability in the extent of absorption would lead to differences in steady-state
      hydroxychloroquine concentrations between patients, potentially contributing to
      the variability in response observed in clinical practice.

PMID- 8156286
TI  - Algodystrophy: an under-recognized complication of minor trauma.
AB  - Algodystrophy is a poorly recognized condition of uncertain aetiology which
      presents with pain and tenderness, vascular instability, swelling and stiffness
      of an affected limb. It is most commonly seen after trauma. In order to ascertain
      its incidence, natural history and the degree of morbidity induced we studied
      prospectively 274 patients with Colles' fracture. Algodystrophy, as judged by the
      presence of bone pain or tenderness, vasomotor symptoms, swelling and stiffness
      of the hand was noted in 28% of patients. There was a significant association
      between the presence of these features (P < 0.0001). The degree of trauma
      sustained was identified as a predisposing factor. Actuarial analysis showed a
      gradual resolution of symptoms. Six months after injury, the proportion of
      patients complaining of pain and swelling had fallen to 20-30%, vascular
      instability and tenderness to 50% and stiffness to 80%. Failure to improve was
      associated with a significant loss of hand function (P < 0.0001). By 1 yr, pain
      and tenderness, vascular instability and swelling had decreased still further but
      stiffness was still apparent in 50%. We believe that algodystrophy is a neglected
      disorder and is far more common than formerly appreciated. Although it often
      resolves spontaneously, it is associated with a significant increase in short
      term morbidity in the majority of patients and persistent dysfunction in a
      minority.

PMID- 8156288
TI  - The cervical spine in psoriatic arthritis: a clinical and radiological study.
AB  - Cervical spondylitis has been reported in 35-75% of patients with PsA. The
      clinical and radiological changes of the cervical spine were evaluated in 75
      patients with PsA. Cervical spine involvement was found in 45% of those examined
      and 36% of patients X-rayed. The pattern of disease was ankylosing in 85% of
      patients, characterized by ankylosis, syndesmophytes and ligamentous
      ossification. Twelve per cent had radiological evidence of cervical spondylitis
      without clinical evidence of disease. The major predictor of cervical spine
      disease was the duration of psoriatic arthropathy. Cervical spondylitis was not
      related to disease severity, extent of skin or nail involvement and neither did
      it reflect any homogeneous pattern of disease.

PMID- 8156287
TI  - Symmetry of radiological features in the wrist and hands of patients with early
      to moderate rheumatoid arthritis: a quantitative microfocal radiographic study.
AB  - Quantitative microfocal radiography was used to assess the degree of symmetry in
      radiological features between the dominant and non-dominant wrist and hands of 51
      patients with early to moderately advanced RA. With few exceptions, erosion size
      and joint space width were bilaterally symmetrical between the dominant and non
      dominant side in: total erosion area and total joint space width; area at each of
      the separate sites of erosion formation, and width at each joint space; and the
      change in these X-ray features over an 18-month study period. Asymmetry in the
      number and size of erosions and joint space occurred in a small number of
      patients within either extremity; these differences were not sustained over the
      study period. In view of this degree of bilateral symmetry, the extent and
      progression of the radiographic features in RA can be assessed from a single
      macroradiograph of either the left or right wrist and hand.

PMID- 8156289
TI  - Light, immunofluorescence and electron microscopy renal biopsy findings as
      predictors of mortality in eighty-five Spanish patients with systemic lupus
      erythematosus.
AB  - This study aimed to define prognostic indicators of death in renal biopsies from
      Spanish patients with SLE. Renal biopsies of eighty-five lupus patients with and
      without clinical nephritis, taken between 1974 and 1987, were reviewed. Samples
      previously processed for light (LM), immunofluorescence (IM) and electron (EM)
      microscopy were analysed blind. Kaplan-Maier curves, log-rank test, and
      multivariate Cox's regression statistical methods were used for comparison of
      biopsy data in relation to patient survival. Univariate analysis showed that
      vascular hyalinosis, glomerular sclerosis, fibrous crescent and chronicity index
      higher than 3 by LM, and intramembranous dense-deposits by EM are predictors of
      poor survival. A multivariate approach confirmed the independent influence of
      vascular hyalinosis, chronicity index higher than 3 and intramembranous deposits.
      A predictive model can be constructed with three LM (hyalinosis, tubular atrophy
      and glomerular sclerosis) and three EM variables (subepithelial, mesangial and
      intramembranous deposits). Selected renal biopsy changes detected by LM and EM
      are therefore predictors of death in patients with lupus. Chronicity markers,
      more than those of activity or severity, are the best prognostic indicators.

PMID- 8156290
TI  - Osteoarthritis of the knee following meniscectomy.
AB  - The relationship between age at meniscectomy and the time to developing OA
      requiring an operation was studied. A total of 63 patients (7.8% of those
      presenting for an operation for OA) had had a previous meniscectomy. It was found
      that there was a strong correlation between the age at meniscectomy and the time
      delay (r = -0.68, P < 0.0001). The equation for the regression line was y = 
      0.68x + 41.8, where y = the delay in years between meniscectomy and operation for
      OA, and x = the age at meniscectomy. It was noted that there were two distinct
      populations, those < or = 35 yr old with a mean delay of 26 yr (95% CI 20.8
      31.4), and those > 35 yr old with a mean delay of 9.8 yr (95% CI 7.5-12.2). The
      development of OA requiring an operation following meniscectomy depends on the
      age at meniscectomy and the time delay. To show an increase rate of OA following
      meniscectomy in a young population would require follow-up of at least 26 yr.

PMID- 8156291
TI  - Pregnancy-associated osteoporosis: report of two cases with long-term bone
      density follow-up.
AB  - Pregnancy-associated osteoporosis is a rare and poorly characterized clinical
      entity. We describe two women, aged 28 and 31 yr, who developed vertebral
      osteopaenia with non-traumatic compression fractures within a few months after
      delivery. In both women secondary causes of osteoporosis were excluded and
      routine laboratory data including indices of calcium metabolism were normal. In
      one patient (Patient 1) spontaneous secretion of IL-1 by cultured blood monocytes
      was elevated 6 months after delivery and a bone biopsy revealed histomorphometric
      indices consistent with accelerated bone remodelling. BMD was measured by
      quantitative computed tomography (QCT) and/or dual energy X-ray absorptiometry
      (DXA). In Patient 1, BMD, measured with QCT, 6 months after delivery was 3.32 Z
      score units below the predicted value for age and sex-matched subjects. At that
      time treatment (phosphate followed by sodium etidronate) was instituted, and QCT
      measurements obtained 24 and 30 months after delivery revealed a BMD of -2.98 and
      -2.67 Z-score units, respectively. The treatment was discontinued just before she
      became pregnant again, and 3 months after the second delivery QCT showed a BMD of
      -3.06 Z-score units. Further BMD assessments were obtained with DXA at 15 and 18
      months after the second delivery, and the BMD values were -1.41 and -1.08,
      respectively. In Patient 2, spine BMD, measured with QCT, 4 and 10 months after
      delivery were -1.68 and -1.59 Z-score units, respectively. At 10, 16 and 22
      months after delivery, BMD was assessed with DXA. The initial measurement with
      this technique disclosed a BMD of 0.52 Z-score units.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8156292
TI  - Ultrasonography of the tibialis posterior tendon in rheumatoid arthritis.
AB  - This work was carried out to assess the frequency of frank rupture of the
      tibialis posterior tendon (TPT) in RA and to determine if other pathology in the
      tendon can be correlated with foot deformity. Clinical, radiographic and
      ultrasonographic signs of TPT pathology were assessed bilaterally in 28 patients
      with RA and hindfoot involvement. The degree of hindfoot pain, the single-heel
      rise test and the tibiocalcaneal angle were assessed clinically. The
      talometatarsal angle was measured on lateral weight-bearing radiographs. Tendon
      continuity and thickness were noted on sonography, both in the study group and in
      a control group of 14 patients. The TPT was significantly thinner in those
      rheumatoid patients with an abnormal single-heel-rise test when compared to those
      patients with a normal test (P < 0.001) and to the control group (P < 0.001). The
      mean thickness in patients with an abnormal test was 1.6 mm, in patients with a
      normal test it was 2.3 mm and in the controls it was 1.9 mm. In the rheumatoid
      group thinning of the tendon was significantly correlated (r = -0.33, P < 0.05)
      with heel valgus as assessed by the tibiocalcaneal angle. It was also
      significantly correlated (r = 0.31, P < 0.05) with pes planus as assessed by the
      talometatarsal angle. Only one case of frank rupture of the TPT was identified.
      There were also significant correlations between TPT thickness and patient age,
      disease duration and steroid therapy, such that tendon attenuation was associated
      with increasing age, longer disease and steroid usage. There was no association
      between TPT thickness and the degree of hindfoot pain.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8156293
TI  - The treatment of sicca features in Sjogren's syndrome: a clinical review.
AB  - Patients with SS often suffer considerable distress due to sicca symptoms and the
      complications of mucosal dryness. Although there are many topical treatments
      available, the literature on their use is scant. This paper describes the
      treatments available and suggests a rationale for the choice of product.

PMID- 8156294
TI  - Mycotic arthritis of the knee due to Madurella grisea.

PMID- 8156295
TI  - Cryptic Wegener's granulomatosis revealed after 18 years.
AB  - A 48-yr-old female is described. She presented with subglottic stenosis requiring
      permanent tracheostomy, followed after 2 yr by an inflammatory polyarthritis,
      treated as rheumatoid. Eighteen years later, a vasculitic illness characterized
      by rash, weight loss, fever, and mononeuritis multiplex drew attention to the
      likelihood of a unifying diagnosis. A solitary lung opacity in the absence of
      nodules elsewhere and a positive ANCA (albeit of perinuclear specificity), made
      the diagnosis of Wegener's granulomatosis most likely. The combined exhibition of
      systemic corticosteroids and immunosuppressive drugs was only required 18 yr
      after onset, and illustrates the relatively benign course that this disorder can
      take.

PMID- 8156296
TI  - Complement degradation products in rheumatoid arthritis synovial fluid.

PMID- 8156297
TI  - Orthopaedic surgeons are always right.

PMID- 8156298
TI  - The way forward for balneotherapy.

PMID- 8156299
TI  - Systemic sclerosis: HLA antigens, autoantibodies and the brain.

PMID- 8156300
TI  - Male lupus and the Loch Ness syndrome.

PMID- 8156301
TI  - Detection of cytomegalovirus, Epstein-Barr virus and herpes virus-6 in patients
      with rheumatoid arthritis with or without Sjogren's syndrome.
AB  - The frequency of latent viral infection by cytomegalovirus (CMV), Epstein-Barr
      virus (EBV) and herpes virus-6 (HHV-6) was investigated in patients with RA with
      or without Sjogren's syndrome (SS) and in normal controls. Virus presence was
      determined by polymerase chain amplification of DNA isolated from peripheral
      blood mononuclear or polymorphonuclear cells and/or saliva-derived
      mononuclear/epithelial cells. Anti-viral antibodies and autoantibodies were also
      assayed. Patients with RA both with and without SS were found to have a
      significantly increased frequency of latent viral infection (two-fold higher, P =
      0.035 for EBV and seven-fold higher, P = 0.018 for HHV-6) compared to normal
      controls but only in cells isolated from saliva. The increased frequency of
      virally infected cells from the saliva of patients with RA, regardless of the SS
      status, when compared to normal controls may reflect the ongoing inflammatory
      process, the impact of therapy and/or a less effective local immune
      responsiveness.

PMID- 8156302
TI  - Association of HLA antigens with anti-Scl-70-antibodies and clinical
      manifestations of systemic sclerosis (scleroderma)
AB  - Thirty patients with systemic sclerosis (scleroderma) and 188 healthy controls
      were studied for class I and class II MHC antigens. All patients with scleroderma
      fulfilled the ARA preliminary criteria for systemic sclerosis. The frequencies of
      HLA antigens B8, DR3 and DR52 were higher in patients with scleroderma as
      compared with controls. Ten patients had anti-Scl-70 antibodies, and four of them
      (40%) had HLA-DR5 antigen compared to 19 of 188 controls (10%), P = 0.013. The
      relative risk for DR5 in anti-Scl-70-positive patients was 3.6 compared to 1.6 of
      DQ3 suggesting the primary significance of DR5 compared to DQ related factors.
      Patients with neurological manifestations had higher frequencies of B8 and DR3
      than those with no neurological manifestations of scleroderma. Our results
      support the view that immunogenetic background is associated with different
      clinical subsets of systemic sclerosis.

PMID- 8156303
TI  - Endothelial cell stimulating angiogenesis factor--a new biological marker for
      disease activity in ankylosing spondylitis?
AB  - Endothelial cell stimulating angiogenesis factor (ESAF) is raised in conditions
      of neovascularization, such as may occur at the endochondral surface of the bone
      growth plate or in association with syndesmophyte formation. Syndesmophytes are
      formed in response to chronic enthesitis. Twenty unselected patients with AS were
      studied and enthesitis was measured clinically using a previously validated
      enthesitis index. Biochemical and haematological markers of disease activity were
      measured along with ESAF. Radiographs were scored for the degree of sacroiliitis
      and syndesmophyte formation and all these measurements were correlated to the
      enthesitis index. ESAF was raised in AS compared with normal controls. ESAF
      correlated positively with the enthesitis index but not with any of the
      biochemical or haematological indices. Higher levels of ESAF were found in those
      with more advanced sacroiliitis. High ESAF activity may be reflecting the
      angiogenic process involved in new bone formation associated with sacroiliitis
      and syndesmophyte formation. ESAF may be a biochemical marker for disease
      activity in AS.

PMID- 8156304
TI  - The prevalence of serum IgG antibodies to type II collagen in American patients
      with rheumatoid arthritis.
AB  - Serum IgG antibody levels to native and denatured bovine type II collagen were
      elevated in 31.5 and 21.5% sera respectively from 200 American patients with RA.
      The prevalence of serum antibodies to native type II collagen is significantly
      higher than previously found in large studies of the prevalence of this
      autoantibody in Britain and Japan when using the same methodology.

PMID- 8156305
TI  - Systemic lupus erythematosus in 61 Oriental males. A study of clinical and
      laboratory manifestations.
AB  - The clinical and laboratory features of 61 oriental male lupus patients were
      compared to those of 86 oriental female patients to determine whether gender
      differences occur. Arthritis was significantly less common in the males.
      Neuropsychiatric disorders were less frequent but the difference did not reach
      statistical significance. Renal disease was the commonest clinical manifestation
      and diffuse proliferative glomerulonephritis the dominant histological finding on
      renal biopsy in the males. The prevalences of leucopenia and antibodies to
      extractable nuclear antigens in particular anti-Ro (SSA) and anti-La(SSB), were
      lower in men. Arthritis and serositis were less common in our oriental males in
      contrast to the caucasian patients. These findings provide further evidence of
      differences between the genders in SLE and suggest racial factors may affect
      clinical presentation.

PMID- 8156306
TI  - Imaging study on the mode of development and changes in avascular necrosis of the
      femoral head in systemic lupus erythematosus: long-term observations.
AB  - To find out when and how avascular necrosis of the femoral head (ANFH) develops
      in patients with SLE who are receiving corticosteroids, we carried out a 3-yr
      prospective study using imaging methods. Twenty-three patients with SLE who were
      free of hip pain and radiographically negative were enrolled in the study.
      Initially, abnormal findings characteristic of ANFH were detected in eight (35%)
      and six (26%) patients on MRI and radionuclide uptake bone scanning,
      respectively. During a 3-yr observation period abnormalities on MRI, bone
      scanning and radiography were found in four, five and four patients, respectively
      and three patients developed hip pain. Analyses of imaging changes demonstrated
      that only a small proportion of patients (2/8, 25%) who initially showed abnormal
      MRI progressed to be radiographically positive for ANFH over the 3 years. High
      doses of corticosteroids over the 3-yr period were to be responsible for the
      emergence of change in MRI abnormalities. It is also suggested that abnormal MRI
      findings tend to develop either within a relatively short interval after the
      start of corticosteroid treatment or are associated with the exacerbation of SLE.

PMID- 8156307
TI  - Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone
      loss.
AB  - We conducted a prospective study of etidronate's effects on corticosteroid
      induced bone loss in postmenopausal women with temporal arteritis for whom high
      dose prednisone therapy was indicated. Group A (n = 10) received etidronate (400
      mg/day for 2 weeks, then 11 weeks off etidronate; four cycles total) and
      prednisone: Group B (n = 10) received only prednisone. Vertebral bone mineral
      density (BMD) was measured blinded by dual X-ray absorptiometry. At 3, 6 and 12
      months, vertebral BMD was significantly (P < 0.01) increased in Group A and
      decreased in Group B, based on mean actual and percent changes in BMD and mean
      changes in BMD Z-score from baseline. Between-group comparisons were also
      significant (P < 0.002) at each time point. No adverse events related to
      etidronate treatment were reported. Our results suggest that corticosteroid
      induced bone loss may be prevented by instituting intermittent cyclical
      etidronate therapy when high-dose prednisone therapy is begun. Further research
      into bisphosphonate use in corticosteroid-induced bone loss (with larger patient
      populations, longer follow-up and fracture assessment) is warranted.

PMID- 8156308
TI  - Yttrium synovectomy in haemophilic arthropathy.
AB  - Between 1987 and 1991 we performed Yttrium-90 (Y-90) silicate radionuclide
      synovectomies on 40 joints of 20 haemophiliac patients with haemophilic
      arthropathy. All were male, their mean age was 31 yr and 15 of the 20 (75%) were
      HIV antibody positive. The number of joint bleeds and amount of factor (VIII and
      IX) replacement given in the 6 months pre- and 6 and 12 months post-radionuclide
      synovectomy was compared. Y-90 silicate synovectomy was shown significantly to
      reduce both the number of joint bleeds (P < 0.001) and factor usage (P < 0.001)
      in the 6 months after the procedure, a result maintained up to 12 months. Depot
      methyl prednisolone was co-administered with Y-90 but thought unlikely to
      contribute to joint response beyond 6 months. The reduction of joint bleeds and
      factor usage was even more dramatic in the 6- to 12-month period post-synovectomy
      although this was not reflected by the P value (P < 0.001). The reduction of
      joint bleeds and factor consumption post-synovectomy was most obvious in elbow
      joints, although the other joints as a group showed a significant reduction.
      Patients who were HIV antibody positive showed considerable improvement up to 12
      months post-treatment, both in reduction of joint bleeds and as a consequence
      factor consumption. This improvement was seen to a lesser extent in the smaller
      HIV-negative group.

PMID- 8156309
TI  - Overall long-term impact of total hip and knee joint replacement surgery on
      patients with osteoarthritis and rheumatoid arthritis.
AB  - All patients with OA or RA entering an orthopaedic waiting list for total hip or
      knee replacement surgery over a period of 2.5 yr were prospectively assessed for
      overall pain (Visual Analogue Scale) and disability (Health Assessment
      Questionnaire) prior to and following their operation at annual intervals for up
      to 5 yr. A total of 293 patients had 335 operations (OA, hip 164; OA, knee 76;
      RA, hip 41; RA, knee 54). A few patients (14) showed a deterioration in pain and
      function 1 yr after surgery, but the remainder showed improvements which took 1
      yr or more to reach maximum and were maintained for at least 3 yr. Although
      greater for OA hip patients, improvements occurred and were maintained in all
      groups, in spite of the polyarticular nature of RA.

PMID- 8156310
TI  - The microbiology of chronic inflammatory arthritis: an historical review.
AB  - Tissues from patients with RA have always been subject to close microbiological
      scrutiny in attempts to determine the pathogenesis of joint inflammation. This
      paper presents an historical review of micro-organisms isolated from patients
      with chronic RA dating from the early days of microbiology in the late 19th
      century until the present day. The relevance of these findings is discussed in
      the light of current hypotheses concerning the role of infection in the aetiology
      of RA.

PMID- 8156311
TI  - Focal infection revisited.
AB  - This paper reviews the theory of focal infection that was widely held to explain
      the aetiology of inflammatory joint disease in the first three decades of this
      century. The theoretical basis for these beliefs and the practical consequences
      for physician and patient alike are examined, as are the results of such radical
      treatments as were applied.

PMID- 8156312
TI  - Towards a measure of patient-perceived handicap in rheumatoid arthritis.
AB  - The impact of chronic disease on an individual depends not only on the severity
      of the disease, but on his/her life role i.e. his/her needs, expectations etc.
      The World Health Organization expresses the impact of chronic disease in terms of
      impairment, disability and handicap, where handicap is the social disadvantage
      resulting from disease. This article argues that the assessment of patient
      perceived handicap is essential to the clinical management of chronic disease
      because it provides the physician with clinically relevant information about the
      meaning of disease for each patient, enabling treatment and intervention to be
      tailored to meet individuals' needs. The development of a method for assessing
      patient-perceived handicap using patient profiles with the object of supplying
      the physician with a simple clinical tool is described.

PMID- 8156313
TI  - A pilot study of the economic cost and clinical outcome of day patient vs
      inpatient management of active rheumatoid arthritis.
AB  - The aims of this pilot study, which compares day patient with inpatient care for
      management of active RA were (i) to test the feasibility of a trial protocol
      design including the method of randomization and the practicality of data
      collection, and (ii) to obtain preliminary information on economic cost and
      clinical outcome of these two methods of management. Twenty consecutive patients
      requiring admission for management of active RA were randomized to receive either
      day patient or inpatient care. All hospital, transport, community and indirect
      costs incurred over a 6-month period from recruitment were collected for each
      patient. Disease activity and clinical outcome were assessed using the Ritchie
      articular index, ESR, Health Assessment Questionnaire, Functional Independence
      Measure and Hospital Anxiety and Depression Scale. The trial protocol was found
      to be feasible and no patient allocated to the day patient group requested or
      required to be transferred to inpatient care. Day care was significantly cheaper
      than inpatient care despite higher transport costs; the total cost of treating 10
      day patients was UK 10,272 pounds compared with 14,528 pounds for 10 inpatients.
      Clinical outcome was comparable in both groups for all parameters studied and
      there was no obvious detrimental effect on patients receiving day care. This
      pilot study demonstrates that day care is feasible and acceptable to patients
      with active RA. The preliminary data suggest that day care is substantially
      cheaper than inpatient care and does not apparently compromise clinical outcome.

PMID- 8156314
TI  - Aplastic anaemia associated with fenbufen: a report of two cases.
AB  - We report two cases of aplastic anaemia occurring in patients after exposure to
      the NSAID fenbufen. In each case, the patient had not been exposed to other drugs
      in this class, and was on no concomitant medication which has previously been
      associated with this complication. Failure of in vitro growth of haemopoietic
      progenitor cells in clonogenic assays confirmed the diagnosis of aplasia, and
      also confirmed that aplasia induced by this agent is not due to the presence of
      any humoral inhibitory factor, but to an intrinsic abnormality in the pluripotent
      stem cells. Aplastic anaemia is a recognized, but extremely rare, complication of
      exposure to NSAIDs of any chemical subtype.

PMID- 8156315
TI  - Lesch-Nyhan syndrome presenting with renal insufficiency in infancy and transient
      neonatal hypothyroidism.
AB  - A 20-day-old male infant presented with acute renal failure. Three weeks later he
      developed acutely swollen, hot, red joints and tophi in his hands and feet. The
      serum uric acid was 2.2 mmol/l (normal 0.13-0.23 mmol/l) and the urinary
      oxypurine/creatinine ratio was 2.26 mmol (normal < 1.5 mmol). Complete deficiency
      of hypoxanthine guanine phosphoribosyl transferase (HGPRT) in intact erythrocytes
      confirmed Lesch-Nyhan syndrome. Neurological development was delayed and self
      mutilation was observed at 22 months. Acute renal failure secondary to crystal
      nephropathy and tophaceous gout are unusual presenting features of this rare
      condition. This child also had transient neonatal hypothyroidism, which is not a
      recognized manifestation of the syndrome.

PMID- 8156316
TI  - Scleroderma and silicone breast implants.
AB  - A 43-yr-old caucasian female presented in July 1992 with an explosive onset of
      diffuse scleroderma following general anaesthesia for orthopaedic surgery. Her
      environmental exposures included silicone breast prosthetic surgery and silica
      exposure, both preceding development of scleroderma. She was DR5-negative, DRw52
      positive. All currently available literature relating to breast implants and
      scleroderma is reviewed and the conclusion drawn that, for currently documented
      US data, there is no evidence to suggest that patients having had breast
      augmentation have rates of scleroderma higher than expected to chance alone.
      However the cause-effect relationship between silicone and scleroderma/other
      connective tissue disease requires, not just anecdotal reports, but a rigorously
      designed study.

PMID- 8156317
TI  - Streptococcus bovis endocarditis presenting as acute spondylodiscitis.

PMID- 8156318
TI  - Pyomyositis due to Escherichia coli in a patient infected by HIV.

PMID- 8156319
TI  - Acetylator phenotypes in primary Sjogren's syndrome.

PMID- 8156320
TI  - Anti-neutrophil cytoplasmic antibodies in Adamantiadis-Behcet's disease.

PMID- 8156321
TI  - Inappropriate modifications of corticosteroid therapy in polymyalgia rheumatica.

PMID- 8156322
TI  - Changes to the invalidity benefit system.

PMID- 8156323
TI  - Rheumatoid arthritis, impairment and mobility.

PMID- 8156324
TI  - Management of peptic ulcer.

PMID- 8156325
TI  - Localization of endocrine pancreatic tumours.

PMID- 8156326
TI  - Epidemiology of varicose veins.
AB  - Assessment and treatment of varicose veins comprises a significant part of the
      surgical workload. In the UK, National Health Service waiting lists suggest that
      there is still considerable unmet need. This review analyses all published data
      on the epidemiology of varicose veins, paying particular regard to the differing
      epidemiological terminology, populations sampled, assessment methods and varicose
      vein definitions, which account for much of the variation in literature reports.
      Half of the adult population have minor stigmata of venous disease (women 50-55
      per cent; men 40-50 per cent) but fewer than half of these will have visible
      varicose veins (women 20-25 per cent; men 10-15 per cent). The data suggest that
      female sex, increased age, pregnancy, geographical site and race are risk factors
      for varicose veins; there is no hard evidence that family history or occupation
      are factors. Obesity does not appear to carry any excess risk. Accurate
      prevalence data allow provision of appropriate resources or at least aid rational
      debate if demand is greater than the resources available.

PMID- 8156327
TI  - Current role of extracorporeal shockwave therapy in surgery.
AB  - In urology the introduction of extracorporeal shockwave therapy brought a
      revolutionary change to the management of urinary calculi. This inspired the
      introduction of shockwave therapy in several fields of surgery; it has been
      applied as a potential alternative to several operative procedures but is still
      experimental. So far, the major application of shockwave therapy has been
      lithotripsy of stones in the gallbladder, common bile duct, pancreatic duct and
      salivary gland ducts. Other applications are in the non-operative management of
      bone healing disturbances and in the inhibition of tumour growth. Steps towards
      selective thrombus ablation and pretreatment of heavily calcified arteries have
      also been made. In this review, the applications of extracorporeal shockwave
      therapy in several areas of surgery are discussed. It is concluded that, for
      selected patients, shockwave treatment may serve as a useful addition to the
      surgical armamentarium.

PMID- 8156329
TI  - Halo compressor for control of venous haemorrhage.

PMID- 8156328
TI  - Venous and non-venous leg ulcers: clinical history and appearance in a population
      study.
AB  - In a defined Swedish population of 270,800, all patients with current chronic leg
      ulcers (827) were identified and a random sample of 382 studied in detail. Ulcers
      of primarily venous cause comprised 54 per cent of the total, giving a point
      prevalence of 0.16 per cent (95 per cent confidence interval 0.15-0.18 per cent).
      Half of all patients experienced their first ulcer episode before the age of 65
      years, a greater proportion (61 per cent, P < 0.0001) in the subgroup with venous
      ulcers. The median duration of ulcer diathesis was significantly longer in
      patients with venous than in those with non-venous lesions (13.4 versus 2.5
      years, P < 0.001). About half the patients with venous and non-venous ulcers had
      had their current lesion for longer than 1 year. Venous ulcers were more often
      recurrent than those of non-venous type (72 versus 45 per cent of patients, P <
      0.0001). Patients with venous ulcers had a significantly higher body mass index
      (P < 0.001). The number of dressing changes performed per week was 1100 per
      100,000 population. The predictive value of 'classical' clinical indicators of
      venous ulcer did not exceed 0.76. To increase the accuracy of diagnosis of venous
      ulcer, clinical examination should be combined with non-invasive 'objective'
      haemodynamic assessment of the venous circulation.

PMID- 8156330
TI  - Reliability of ankle:brachial pressure index measurement by junior doctors.
AB  - Ankle:brachial pressure index (ABPI) measurements are often performed by junior
      medical staff with little experience of the technique. The accuracy of such
      measurements is unknown. Two newly qualified doctors with no training in the use
      of Doppler ultrasonographic flowmeters performed ABPI measurement in 38 limbs
      (experiment 1). Two other newly qualified doctors then underwent a formal
      training session before, as well as continuous instruction during, ABPI
      measurements in 23 limbs (experiment 2). The doctors' measurements were compared
      with those obtained by experienced vascular technicians. The mean difference in
      ABPI measurement between the doctors and technicians in experiment 1 was greater
      than that in experiment 2 at both the dorsalis pedis (P < 0.05) and posterior
      tibial arteries. Nearly 30 per cent of the doctors' ABPI measurements in
      experiment 1 differed from those of the technicians by more than 0.15, in
      comparison with only 15 per cent of the measurements performed in experiment 2.
      Junior doctors should undergo formal training before performing ABPI
      measurements.

PMID- 8156331
TI  - Femoropopliteal angioplasty for severe limb ischaemia.
AB  - Fifty patients undergoing 51 percutaneous transluminal angioplasties of the
      femoropopliteal segment for severe limb ischaemia were reviewed regularly. They
      comprised 30 men and 20 women of median age 70 (range 56-85) years. There were
      two deaths within 30 days. At 2 years the cumulative patient survival rate was 60
      per cent. Eleven angioplasties were technical failures, 25 failed in the first 6
      months and 14 were successful at 6 months' follow-up; in addition one patient
      died from myocardial infarction within 30 days of technically successful
      angioplasty. Subsequent vascular procedures were successful in 11 limbs following
      failed angioplasty. The primary limb survival rate was 42 per cent at 2 years.
      There were eight major complications after angioplasty, requiring amputation in
      five instances. Of the 23 long occlusions (greater than 5 cm) that were
      recanalized and dilated, 22 procedures failed within 6 months. The run-off score
      and diabetic status did not predict outcome. In this group of patients
      angioplasty had a low durability. Dilatation of long occlusions is associated
      with high rates of reocclusion and, on the basis of these results, should not be
      performed.

PMID- 8156332
TI  - Endoscopic transthoracic sympathectomy as adjuvant treatment for critical upper
      limb ischaemia.

PMID- 8156333
TI  - Experimental experience with a temporary intraluminal heparin-bonded polyurethane
      arterial shunt.
AB  - After vascular injury, intraluminal arterial shunting may be employed if
      definitive surgery must be delayed. This paper describes use of a heparin-bonded
      polyurethane shunt to restore distal circulation after ligation of the femoral
      artery in sheep. In studies to determine tissue viability for 12 h after
      insertion into the femoral artery, five of seven shunts remained patent. In
      another series of experiments to study tissue viability after limb ischaemia, the
      femoral artery was ligated and a tight Esmarch bandage applied to the limb for 6
      h before shunt insertion. The shunt remained patent for 12 h in five of six
      cases. Nearly all shunt failures occurred shortly after placement and were
      attributable to intimal damage arising from difficulties during insertion.

PMID- 8156334
TI  - Control of lumbar artery bleeding during aortic aneurysm repair.

PMID- 8156335
TI  - Audit of emergency preoperative resuscitation.
AB  - A total of 148 patients of mean age 61 years with acute gastrointestinal disease
      who were assessed as requiring preoperative resuscitation were studied. Overall,
      the mortality rate was 14.2 per cent and the morbidity rate 50.7 per cent.
      Resuscitation was associated with a mean(s.e.m.) improvement in predicted
      mortality rate of 4.2(0.8) per cent and in morbidity rate of 4.3(0.7) per cent.
      However, there was a group of patients in whom resuscitation was unsuccessful,
      despite there being no apparent difference in duration or methods of
      resuscitation from those of the rest of the population studied. A poor response
      to resuscitation was found in 28 patients; this was commoner in the elderly (P <
      0.001) and in women (P < 0.05). Complications were more frequent in patients
      failing to improve with resuscitation (P < 0.001). In the group deteriorating
      despite resuscitative (P < 0.001). In the a greater proportion of patients with a
      perforated viscus (P < 0.001), whereas intestinal obstruction was less common (P
      < 0.05). This study demonstrates that resuscitation can be audited and
      quantified. Preoperative resuscitation appears to be beneficial, but there is a
      group that may benefit from synchronous surgery and resuscitation.

PMID- 8156336
TI  - Haemorrhage following penetrating gluteal trauma.

PMID- 8156337
TI  - Impact of thymopentin on the incidence and severity of postoperative infection: a
      randomized controlled trial.
AB  - The effectiveness of perioperative administration of thymopentin in preventing
      postoperative infection was evaluated in 206 patients with cancer (54 gastric,
      152 colorectal) who underwent elective major surgery. Comparable subsets of
      patients were obtained with respect to age (proportion over 65 years) and
      nutritional status (patients with serum albumin level less than 30 milligrams or
      weight loss of 10 per cent or more of usual body-weight were considered to be
      malnourished). Patients were then randomly assigned to a control group or to a
      group receiving thymopentin. All patients received perioperative short-term
      antibiotic prophylaxis and postoperative parenteral nutrition. Levels of CD3-,
      CD4- and CD8-positive T cell subsets were evaluated before and after surgery in
      20 (ten elderly) patients from each group. The severity of postoperative
      infection was evaluated using a sepsis score. In elderly patients thymopentin
      prevented the postoperative drop in CD3- and CD4-positive T cell subpopulations
      that was observed in controls (P < 0.05d). The postoperative infection rate was
      17.5 per cent in the group given thymopentin and 24.3 per cent in controls (P not
      significant). The mean (s.d.) sepsis score was 6.7 (3.1) in the group receiving
      thymopentin and 9.4 (5.8) in controls (P not significant). Considering only
      elderly patients, the mean (s.d.) sepsis score was significantly lower in those
      treated with thymopentin than in control patients (6.9(2.1) versus 11.3(4.7)). In
      conclusion, administration of thymopentin did not significantly reduce the
      postoperative infection rate. However, it prevented the drop in number of CD3-
      and CD4-positive T cells after operation and reduced the severity of
      postoperative infection in elderly patients.

PMID- 8156338
TI  - Prediction of outcome using the Mannheim peritonitis index in 2003 patients.
      Peritonitis Study Group.
AB  - Early prognostic evaluation of abdominal sepsis is desirable to select high-risk
      patients for more aggressive therapeutic procedures and to provide objective
      classification of the severity of disease. The reliability of the Mannheim
      peritonitis index was assessed and its predictive power for different populations
      examined in a study of 2003 patients from seven centres in three European
      countries. The prevalence of risk factors varied considerably between the groups.
      For a threshold index score of 26, the sensitivity was 86 (range 54-98) per cent,
      specificity 74 (range 58-97) per cent and accuracy 83 (range 70-94) per cent in
      predicting death. For patients with a score less than 21 the mean mortality rate
      was 2.3 (range 0-11) per cent, for score 21-29 22.5 (range 10.6-50) per cent and
      for score greater than 29 59.1 (range 41-87) per cent. The mean index score and
      mean mortality rate correlated in the different groups, reflecting a homogeneous
      standard of therapy for peritonitis. The Mannheim peritonitis index provides an
      easy and reliable means of risk evaluation and classification for patients with
      peritoneal inflammation.

PMID- 8156339
TI  - Tumour necrosis factor-mediated release of plasminogen activator inhibitor 1 by
      human peritoneal mesothelial cells.
AB  - Human mesothelial cells synthesize plasminogen activator inhibitor (PAI) 1 in
      inflamed peritoneal tissue. The role of tumour necrosis factor (TNF) in the
      mediation of this response was studied. Postoperative peritoneal drain fluid
      contained both TNF and PAI-1. Peak levels of TNF at 4 h (median 271 pg/ml)
      preceded a rise in PAI-1 concentration, which peaked at 18 h (median 943.1
      ng/ml). Thus TNF may mediate increased PAI-1 release in inflamed peritoneum. TNF
      significantly increased the mean(s.e.m.) release of PAI-1 by human peritoneal
      mesothelial cells in vitro at 4 h (control 1.84(0.17) ng/micrograms versus TNF
      2.37(0.17) ng/micrograms, P < 0.05), 6 h (2.53(0.09) versus 3.88(0.46)
      ng/micrograms, P < 0.05), 18 h (0.50(0.02) versus 1.04(0.11) ng/micrograms, P <
      0.05) and 24 h (0.87(0.05) versus 1.35(0.11) ng/micrograms, P < 0.05). TNF may be
      an important mediator of PAI-1 production by human mesothelial cells during
      peritoneal inflammation.

PMID- 8156340
TI  - Timing of surgery in relation to the menstrual cycle in premenopausal women with
      operable breast cancer.
AB  - Recent studies have suggested that the timing of surgery in relation to the
      menstrual cycle might influence survival of premenopausal women with operable
      breast cancer. The data of 96 premenopausal patients who underwent primary
      surgery for operable breast carcinoma between 1975 and 1988 were analysed. At 10
      years, disease-free and overall survival rates of patients whose initial surgery
      was 1-12 days after the starting date of the last menstrual period (follicular
      phase) were significantly poorer compared with survival of those who underwent
      operation more than 12 days after the last menstruation (luteal phase) (disease
      free survival rate 40 versus 72 per cent, P = 0.002; overall survival rate 40
      versus 79 per cent, P = 0.001). These differences in survival remained
      significant in a second analysis based on the menstrual phase at the time of both
      initial and definitive operation. Menstrual phase had the greatest impact on the
      survival of patients with positive axillary nodes (P = 0.009). Prospective
      studies are required to elucidate the relationship between the timing of all
      surgical procedures during the menstrual cycle and survival.

PMID- 8156341
TI  - Stereotactic cytology in a regional breast-screening programme.
AB  - Stereotactic localization and fine-needle aspiration are new procedures for the
      management of non-palpable mammographic abnormalities. In this prospective study,
      stereotactically guided cytology with immediate reporting was performed before
      biopsy in a consecutive series of 166 patients with screen-detected non-palpable
      abnormalities. All specimens were obtained by multiple stereotactically guided
      passes with a 22-G Franzen needle and graded as: 1, acellular or inadequate; 2,
      benign; 3, atypical, probably benign; 4, probably malignant; or 5, malignant.
      After definitive surgery all tumours were staged according to the Union
      Internacional Contra la Cancrum classification. Of 71 patients with malignancy,
      56 were correctly diagnosed by cytology before operation. Twelve patients with
      malignancy had grade 1 cytology and 50 of the 52 with grade 2 cytology had benign
      disease. This study confirms that stereotactic cytology is a valuable diagnostic
      test in a breast-screening programme.

PMID- 8156342
TI  - Ultrasonography as a method of measuring breast tumour size and monitoring
      response to primary systemic treatment.
AB  - Accurate measurement of change in tumour size is a prerequisite for the use of
      response-based regimens of primary systemic therapy for breast cancer. This study
      evaluated the accuracy of clinical assessment, mammography and ultrasonography in
      measuring tumour size and in monitoring response to treatment. Size was
      determined during the week preceding surgery and actual size measured from
      resected specimens. Sequential measurements were performed in 35 patients
      undergoing primary systemic treatment. There was moderate correlation between
      pathological and clinical size (n = 51, r2 = 0.68, P < 0.0001). Close correlation
      with pathological tumour size was observed for mammographic (n = 45, r2 = 0.84, P
      < 0.0001) and ultrasonographic (n = 52, r2 = 0.89, P < 0.0001) tumour size.
      Response was correctly evaluated by clinical assessment in 31 of 35 patients, by
      mammography in 20 of 35 and by ultrasonography in 31 of 35. Actual tumour size
      can be measured accurately by available imaging techniques but ultrasonography is
      the most practical and accurate method for monitoring response.

PMID- 8156343
TI  - Recurrent laryngeal nerve palsy after thyroid gland surgery.
AB  - Risk factors for recurrent laryngeal nerve (RLN) lesions after thyroid gland
      surgery were evaluated retrospectively in 1026 patients. RLN palsy occurred in
      5.9 per cent; the incidence of permanent palsy was 2.4 per cent as 59 per cent of
      paralyses were transient. For euthyroid nodular goitre, Graves' disease, chronic
      lymphocytic thyroiditis, recurrent goitre and thyroid carcinoma, permanent nerve
      damage occurred in 1.7, 4, 5, 3.8 and 8 per cent of patients respectively. In
      relation to the number of nerves at risk, the incidence of permanent RLN palsy
      was 1.1 per cent for subtotal lobectomy and 4.0 per cent for total lobectomy. The
      overall incidence of permanent RLN palsy was 1.8 per cent of nerves at risk.
      There was no statistically significant difference between the number of RLN
      paralyses occurring after nerve exposure and that occurring after non-exposure in
      subtotal lobectomy, but in total lobectomy the permanent palsy rate increased
      from 3.8 to 7 per cent when the nerve was not exposed or identified (P < 0.01).
      Underlying thyroid disease, the extent of resection and exposure of the nerve in
      total lobectomy are risk factors for both transient and permanent RLN palsy.

PMID- 8156344
TI  - Radical systematic mediastinal lymphadenectomy in non-small cell lung cancer: a
      randomized controlled trial.
AB  - The value of radical systematic lymphadenectomy in the treatment of bronchial
      carcinoma is controversial. In a randomized controlled clinical trial, radical
      lymphadenectomy was compared with conventional node dissection in 182 patients
      with non-small cell lung cancer. Comparison of short-term results revealed a
      significantly longer operating time in those undergoing systematic
      lymphadenectomy, but overall morbidity and mortality rates were comparable
      between groups. However, there were complications associated with radical
      lymphadenectomy such as prolonged air leakage and haemorrhage. Interim analysis
      of results at a median follow-up of 26.8 months showed no significant influence
      of radical lymphadenectomy on local recurrence-free interval, metastasis-free
      interval or cancer-related survival. In conclusion, radical systematic
      lymphadenectomy is a safe operation that leads to a better staging of non-small
      cell lung cancer, but its prognostic benefit is questionable.

PMID- 8156345
TI  - Right thoracoscopically assisted oesophagectomy for cancer.
AB  - Thoracoscopic mobilization was performed in nine patients with oesophageal
      cancer. Five principles emerged as essential for successful dissection: (1) the
      selection of patients with mobile oesophageal tumours without evidence of local
      invasion; (2) double-lumen anaesthesia and complete collapse of the right lung
      during surgery; (3) simultaneous use of a flexible gastroscope; (4) high-quality
      illumination; and (5) minimal blood loss during dissection. The surgeon should
      have adequate training in thoracic operations. Further experience should permit
      mediastinal lymph node dissection. Postoperative pulmonary complications were
      common, requiring prolonged intensive care management. Widespread adoption of the
      technique cannot be recommended.

PMID- 8156346
TI  - Implications of upright gastro-oesophageal reflux.
AB  - The presentation, oesophageal profile and management of 27 symptomatic patients
      with daytime (upright) gastro-oesophageal reflux only is reported. Oesophagitis
      was a presenting feature in 11 patients and its development was most closely
      correlated with postprandial reflux, which was characterized by cumulative acid
      exposure rather than by clearance abnormalities. Upright reflux was not
      associated with a hypotensive lower oesophageal sphincter or with oesophageal
      dysmotility. Antireflux surgery is indicated when conservative measures fail and
      was not associated with gas-bloat syndrome after operation.

PMID- 8156347
TI  - Distal splenorenal shunting for bleeding gastric varices.
AB  - In patients with bleeding gastric varices from causes other than splenic vein
      thrombosis, endoscopic sclerotherapy and ablative surgery have yielded poor
      results. Over a 3-year period starting in June 1989, a total of 30 distal
      splenorenal shunts were performed prospectively on 19 paediatric and 11 adult
      patients with bleeding gastric varices and good liver function. The mean (s.d.)
      age was 17(12) (range 6-50) years; there were 20 male and ten female patients of
      whom six had cirrhosis, four non-cirrhotic portal fibrosis and 20 portal vein
      thrombosis. Two patients died and two more had shunt thrombosis; all four were
      considered failures of treatment. Hypersplenism was present in 15 patients but
      reverted to normal in 13. In 26 patients the gastric varices disappeared.
      Concomitant oesophageal varices were present in 22 patients and showed marked
      regression, with no rebleeding over a mean (s.d.) follow-up of 21(10) (range 7
      39) months. A distal splenorenal shunt was effective in controlling gastric
      variceal haemorrhage in 26 of 30 patients in whom liver function was well
      preserved.

PMID- 8156348
TI  - Highly selective devascularization for bleeding oesophagogastric varices.
AB  - Between 1975 and 1984, 419 patients with bleeding oesophagogastric varices were
      subjected to the simplified operation of highly selective devascularization. All
      but three were available for follow-up at 5-10 years. The overall mortality rates
      for urgent and elective operation were 8 and 2 per cent respectively. The overall
      recurrent bleeding rates at 1, 5 and 10 years were 8 per cent, 13 per cent (15
      per cent of survivors) and 17 per cent (24 per cent of survivors). The overall
      survival rates at 1, 5 and 10 years were 87, 76 and 57 per cent. Recurrent
      bleeding was usually controlled by endoscopic sclerotherapy and less often by
      reoperation. Highly selective devascularization controlled bleeding in emergency
      and elective situations without compromising hepatic function.

PMID- 8156349
TI  - Accuracy of clinical diagnosis of direct and indirect inguinal hernia.

PMID- 8156350
TI  - Preperitoneal approach to irreducible inguinal hernia in infants.

PMID- 8156351
TI  - Improved sensitivity of colour Doppler flow imaging of colorectal hepatic
      metastases using galactose microparticles: a preliminary report.
AB  - The clinical application of ultrasonographic contrast agents in colour Doppler
      flow imaging of hepatic tumours is receiving increasing attention. Levovist is a
      suspension of galactose microparticles that provides reproducible concentrations
      of stabilized air bubbles with transpulmonary stability. Its effect on colour
      Doppler imaging was assessed in 26 patients with colorectal cancer and
      histologically proven hepatic metastases. Colour Doppler flow imaging was
      performed before and after intravenous injection of 10 ml Levovist 300 mg/ml. At
      5-10 s after injection there was significant enhancement of the hepatic lesions
      with colour Doppler signals in 23 patients, lasting for a mean(s.d.) of 180(45)
      s. A consistent pattern of colour Doppler signal was observed, with increased
      enhancement predominantly around the tumour periphery and little or no central
      enhancement. These data suggest that Levovist may increase the sensitivity and
      specificity of colour Doppler flow imaging of colorectal hepatic metastases.

PMID- 8156352
TI  - Resection of 'recurrent' colorectal metastases to the liver.
AB  - Hepatic resection is the only treatment for patients with colorectal cancer
      metastatic to the liver that has resulted in long-term survival. This apparent
      efficacy of hepatectomy has prompted efforts to expand the surgical approach for
      disease progression within the liver. A review of personal experience and of the
      literature was performed in an attempt to define the role of surgery for disease
      progression. Twenty-one patients who underwent hepatic resection between 1983 and
      1991 for isolated disease progression in the liver were retrospectively reviewed.
      The median follow-up of patients still alive was 1.7 years (range 4 months to 4.5
      years). The median survival from the date of repeat hepatic resection was 3.4
      years with an estimated actuarial survival rate of 43 per cent at 4 years. These
      patients experienced no significant morbidity and the mortality rate was 5 per
      cent. Hepatic resection of metastatic colorectal carcinoma can produce long-term
      survival without prohibitive risk. These findings support an aggressive surgical
      approach for metastatic progression in the liver from colorectal carcinoma.

PMID- 8156353
TI  - Compartment syndrome in experimental chronic obstructive pancreatitis: effect of
      decompressing the main pancreatic duct.
AB  - Chronic pancreatitis is characterized by persistent and severe pain, which can be
      relieved by decompression of the main pancreatic duct (MPD). Both ductal and
      interstitial pressures have been shown to be increased in chronic pancreatitis in
      patients. A study was carried out of pancreatic interstitial pressure and
      pancreatic blood flow in normal cats and those in which chronic obstructive
      pancreatitis had been induced 5 weeks earlier to determine the effect of
      decompression of the MPD. In the normal pancreas, median(interquartile range
      (i.q.r.)) basal interstitial pressure was 0.05(1.2) mmHg and median(i.q.r.) basal
      pancreatic blood flow 58.3(24.3) ml per min per 100 g. Secretory stimulation did
      not change the interstitial pressure significantly, but was associated with a 40
      per cent increase in median(i.q.r.) blood flow to 81.8(45.8) ml per min per 100
      g. In contrast, in chronic obstructive pancreatitis, the median(i.q.r.) basal
      interstitial pressure was 2.0(1.5) mmHg, which was significantly higher than in
      the normal gland, and median(i.q.r.) pancreatic blood flow was 38.3(9.8) ml per
      min per 100 g, significantly lower than in the normal pancreas. Furthermore,
      secretory stimulation was associated with a significant increase in
      median(i.q.r.) interstitial pressure to 3.3(1.6) mmHg and a simultaneous decrease
      in median(i.q.r.) blood flow to 31.5(13.7) ml per min per 100 g. After
      decompression of the MPD in cats with chronic obstructive pancreatitis, the
      median(i.q.r.) basal interstitial pressure was 2.0(1.4) mmHg and on secretory
      stimulation 1.8(1.5) mmHg. Decompression thus prevented the increase in
      interstitial pressure seen in the animals with obstruction. In contrast, ductal
      decompression improved the median(i.q.r.) basal pancreatic blood flow to
      45.9(38.4) ml per min per 100 g and, furthermore, this increased significantly on
      secretory stimulation to a median(i.q.r.) of 81.4(47.8) ml per min per 100 g.
      Decompression thus restored the normal pattern of secretory hyperaemia. Within
      the confines of this model, these observations demonstrate that chronic
      obstructive pancreatitis exhibits a compartment syndrome that is relieved by duct
      drainage.

PMID- 8156354
TI  - Efficacy of octreotide in the prevention of complications of elective pancreatic
      surgery. Italian Study Group.
AB  - A placebo-controlled double-blind multicentre study, with randomization into
      parallel groups, was performed to determine whether perioperative subcutaneous
      administration of octreotide 0.1 mg every 8 h reduces the rate of complications
      specifically related to pancreatic surgery. In all, 252 patients were evaluated
      (153 men, 99 women; mean(s.e.m.) age 53.1(0.8) years) who had pancreatic or
      periampullary tumour or other duodenal disease (157 patients) or chronic
      pancreatitis (95) and were undergoing elective pancreatic resection (100
      Whipple's procedure, 60 distal resection, 12 others), pancreaticojejunostomy (66)
      or enucleation of pancreatic lesions (14). The proportion of patients with
      complications was significantly lower in the group treated with octreotide than
      in the placebo group (15.6 versus 29.2 per cent, P = 0.01). Octreotide thus
      appears to reduce substantially the risk of complications related to elective
      pancreatic surgery. Moreover, treatment acceptability was high.

PMID- 8156356
TI  - Postoperative immunological function and jaundice.
AB  - The effects of operative trauma and obstructive jaundice on systemic immunity
      were studied in a rat model, using the delayed-type hypersensitivity response to
      2,4-dinitro-1-fluorobenzene as a measure of systemic immune responsiveness.
      Midline laparotomy caused a significant decrease in the mean(s.e.m.) delayed-type
      hypersensitivity response 1 week after operation (4.6(1.3) versus 19.0(2.2) per
      cent for controls). The response returned to control levels by 2 weeks (14.6(3.1)
      per cent). Common bile duct ligation and division resulted in a significantly
      depressed hypersensitivity response at 2 and 3 weeks (6.8(2.0) and 8.4(1.6) per
      cent respectively). The expected decrease in the response at 1 week in these
      animals was not observed (mean(s.e.m.) 12.7(2.7) per cent), suggesting a possible
      role for the normal liver in the induction of postoperative immune depression.
      Impaired function of the reticuloendothelial system was induced in non-jaundiced
      animals by Kupffer cell ablation following intraportal infusion of lambda
      carrageenan. A similar prevention of postoperative immune hyporesponsiveness was
      observed (mean(s.e.m.) 10.4(1.0) versus 10.4(1.6) per cent for controls). Hepatic
      Kupffer cells play an important role in the induction of postoperative immune
      depression.

PMID- 8156355
TI  - An inflated condom as a packing device for control of haemorrhage.

PMID- 8156357
TI  - Laparoscopic drainage of postoperative pelvic lymphocele.

PMID- 8156358
TI  - Peritoneal aspiration cytology as a diagnostic aid in acute appendicitis.
AB  - A total of 110 consecutive patients presenting to one surgical firm with
      suspected acute appendicitis underwent peritoneal aspiration cytology. Aspiration
      was successful in 108 patients and 44 were positive. Patients with a positive
      result underwent emergency surgery; 42 had histologically proven acute
      appendicitis and two peritonitis of other causes. Seven patients with a negative
      result underwent appendicectomy; four had acute appendicitis and three a normal
      appendix. Peritoneal aspiration cytology had a sensitivity for acute appendicitis
      of 91 per cent and a specificity of 94 per cent. The positive predictive value of
      the test was 95 per cent and the negative predictive value 94 per cent. The
      negative appendicectomy rate was 10 per cent overall and 11 per cent in women of
      reproductive age. Peritoneal aspiration cytology is a useful diagnostic test in
      the management of patients with suspected acute appendicitis.

PMID- 8156359
TI  - 'Cough sign': a reliable test in the diagnosis of intra-abdominal inflammation.

PMID- 8156360
TI  - Anorectal function after restorative proctocolectomy and low anterior resection
      with coloanal anastomosis.
AB  - Anorectal manometry and electromyography were studied in 17 patients before and
      after restorative proctocolectomy with stapled pouch-anal anastomosis, in ten
      patients before and after low anterior resection with stapled coloanal
      anastomosis, and in 35 normal controls. More than 80 per cent of patients in both
      groups developed abnormal oscillation of anal pressure after operation (amplitude
      15-60 (median 25) cmH2O, frequency 4-10 (median 8) per min) and showed no anal
      relaxation in response to intermittent neorectal distension. All patients lost
      discriminative rectal sensation and none could perceive a normal desire to
      defaecate. Patients with postoperative soiling had a greater amplitude of anal
      pressure oscillation and lower minimum basal pressure, although those who
      underwent coloanal anastomosis had a greater risk of incontinence because of
      large asynchronous oscillations in neorectal pressure. The common
      pathophysiological features after restorative proctocolectomy and coloanal
      anastomosis probably relate to damage to the autonomic and enteric nerve
      supplies. The presence of an unstable internal anal sphincter may be an important
      cause of postoperative nocturnal incontinence.

PMID- 8156361
TI  - Motor determinants of incontinence after ileal pouch-anal anastomosis.
AB  - Anal canal pressure gradient and ileal pouch motor activity were studied in
      continent and incontinent patients after ileal pouch-anal anastomosis. A
      multichannel microtransducer catheter was positioned in eight continent and eight
      incontinent patients 15 months or more after operation and 24-h ambulatory motor
      activity recorded. Resting anal pressures were significantly lower for
      incontinent patients during the day and night. The frequency of high-pressure
      waves was identical in both groups, but peak pressures were higher for
      incontinent patients. For continent patients, each high-pressure wave was
      accompanied by a rapid increase in anal canal pressure such that pressure in the
      pouch was always less than that in the anal canal. For incontinent patients this
      response was often absent. Incontinent patients had lower resting pressure, more
      prolonged anal canal relaxation, higher amplitude high-pressure waves and a non
      responsive anal canal; the anal canal pressure gradient was therefore frequently
      reversed.

PMID- 8156362
TI  - Ileal bile acid malabsorption in colonic Crohn's disease.

PMID- 8156363
TI  - Control of colonic variceal haemorrhage by long-term octreotide administration.

PMID- 8156364
TI  - Gallbladder dysplasia in patients with familial adenomatous polyposis.

PMID- 8156365
TI  - Restorative proctocolectomy and covering ileostomy.

PMID- 8156366
TI  - Lateral lymph node dissection for rectal carcinoma below the peritoneal
      reflection.
AB  - Lateral lymph node dissection has been advocated for advanced low rectal tumours.
      However, its benefit is debatable because of the possibility of postoperative
      bladder and sexual impairment. To assess the role of lateral lymph node
      dissection 95 patients who underwent the procedure between 1981 and 1991 were
      reviewed and compared with 83 who had resection of rectal cancer without lateral
      node dissection. Only ten (11 per cent) of the 95 patients had lateral lymph node
      involvement; all had Dukes' C tumours. Lymphovascular invasion was present in
      50.6 per cent of all patients and neural invasion in 27 per cent of 65 examined
      specimens. Local recurrence, distant metastasis and overall 5-year survival rates
      were 7, 9 and 76 per cent respectively in patients undergoing extended
      lymphadenectomy and 16, 7 and 72 per cent respectively in those who had resection
      alone. There were no statistically significant differences in survival between
      the two groups for any Dukes' stage. Recurrence, metastasis and survival were
      related more to venous or neural invasion and tumour spread than to node
      dissection. These results demonstrate that patients with Dukes' A tumours do not
      benefit from lateral lymph node dissection, and that local recurrence rates in
      those with Dukes' B and C lesions are not significantly decreased. It is
      concluded that extended lymphadenectomy is unlikely to provide significant
      benefit to patients with low rectal cancer.

PMID- 8156367
TI  - Spreading extraperitoneal cellulitis following perirectal sepsis.

PMID- 8156368
TI  - Anorectal myotomy combined with anterior resection in the treatment of
      Hirschsprung's disease.
AB  - A total of 42 patients with biopsy-proven Hirschsprung's disease were treated by
      anorectal myotomy or myectomy, alone or combined with anterior resection. Myotomy
      is a simple and complication-free procedure. The results compare favourably with
      those of other operative procedures for this condition.

PMID- 8156369
TI  - Abdominal resection rectopexy with pelvic floor repair versus perineal
      rectosigmoidectomy and pelvic floor repair for full-thickness rectal prolapse.
AB  - A randomized trial was performed to compare abdominal resection rectopexy and
      pelvic floor repair (n = 10) with perineal rectosigmoidectomy and pelvic floor
      repair (n = 10) in elderly female patients with full-thickness rectal prolapse
      and faecal incontinence. There were no recurrences of full-thickness prolapse
      following resection rectopexy but one after rectosigmoidectomy. Continence to
      liquid and solid stool was achieved in nine patients, with faecal soiling
      reported in only two, after resection rectopexy and in eight, with soiling in
      six, following rectosigmoidectomy. The median (range) frequency of defaecation
      was only 1 (1-3) per day following resection rectopexy compared with 3 (1-6) per
      day after rectosigmoidectomy. There was an increase in the mean(s.d.) maximum
      resting pressure after resection rectopexy (19.3(15.28) cmH2O) compared with a
      reduction following rectosigmoidectomy (-3.4(13.75) cmH2O) (P = 0.003).
      Mean(s.d.) compliance was also greater after resection rectopexy than following
      rectosigmoidectomy (3.9(0.75) versus 2.2(0.78) ml/cmH2O, P < 0.001). Abdominal
      resection rectopexy gives better functional and physiological results than
      perineal rectosigmoidectomy.

PMID- 8156370
TI  - Postanal repair for faecal incontinence persisting after rectopexy.
AB  - Eleven patients (nine women) with persistent faecal incontinence after rectopexy
      for rectal prolapse were treated by postanal repair. Follow-up data, including
      clinical and anorectal physiology, at 5-8 years (median 76 (range 64-95) months)
      were available for nine patients. At long-term follow-up, seven of the nine
      patients had improved continence (two were continent to solid and liquid stools,
      and five to solid stool). One patient required a colostomy. Median (range)
      physiological findings before and after postanal repair in the nine patients
      were: anal canal length 2.3 (1.5-3.0) versus 3.5 (2.0-5.5) cm (P < 0.05); resting
      anal pressure 20 (0-49) versus 35 (10-55) cmH2O (P < 0.05); perineal descent 2 (1
      3) versus 0 (3 to -0.2) cm; and mean pudendal nerve terminal motor latency 2.35
      (2.0-3.1) versus 2.85 (2.3-3.4) ms.

PMID- 8156371
TI  - Comparison of emergency and elective haemorrhoidectomy.
AB  - A total of 704 patients with symptomatic prolapsed haemorrhoids were operated on
      over a 24-month period. Overall, 500 underwent elective haemorrhoidectomy for
      symptomatic prolapsed haemorrhoids and 204 emergency haemorrhoidectomy for
      acutely prolapsed, thrombosed or gangrenous haemorrhoids. The mean age was 43
      (range 16-80) years in patients undergoing elective surgery and 42 (range 20-86)
      years in those receiving emergency procedures. After elective surgery 27 patients
      (5.4 per cent) had an episode of secondary haemorrhage; ten (2.0 per cent)
      required blood transfusion and six (1.2 per cent) needed surgical haemostasis.
      After emergency surgery, ten patients (4.9 per cent) developed secondary
      haemorrhage; four (2.0 per cent) required blood transfusion and two (1.0 per
      cent) surgical haemostasis. Twelve patients (5.9 per cent) developed anal
      stenosis after an emergency procedure compared with 15 (3.0 per cent) after
      elective operation. None of the patients in either group developed portal
      pyaemia. After elective surgery 26 patients (5.2 per cent) developed a degree of
      incontinence (eight to flatus, 15 to liquids, three to solids) as did nine
      patients (4.4 per cent) after emergency procedures (three to flatus, five to
      liquids, one to solids). Recurrent haemorrhoids were found in 38 patients (7.6
      per cent) after elective surgery and in 14 (6.9 per cent) after an emergency
      procedure.

PMID- 8156372
TI  - Elective hepatic resection for benign and malignant liver disease: early results.

PMID- 8156373
TI  - Delayed perforation of the colon following colonoscopic biopsy.

PMID- 8156374
TI  - Suture length to wound length ratio and healing of midline laparotomy incisions.

PMID- 8156375
TI  - Latex T tubes: a warning.

PMID- 8156376
TI  - Venous assessment using air plethysmography: a comparison with clinical
      examination, ambulatory venous pressure measurement and duplex scanning.

PMID- 8156377
TI  - Extensive versus limited lymph node dissection for gastric cancer: a comparative
      study of 320 patients.

PMID- 8156378
TI  - Prognostic relevance of systematic lymph node dissection in gastric carcinoma.

PMID- 8156379
TI  - Perinatal administration of diazepam alters sexual dimorphism in the rat
      accessory olfactory bulb.
AB  - The present study examines the effects of pre and/or early postnatal
      administration of diazepam on the mitral cell and on the light and dark granule
      cell populations in the sexually dimorphic accessory olfactory bulb of the rat.
      Quantitative differences related to sex were observed in the numbers of the three
      types of neurons, with vehicle males showing greater numbers of cells than
      vehicle females. The number of mitral cells in males decreased to the levels
      shown by female rats following prenatal and pre-postnatal diazepam treatments,
      whereas the DZ treatments did not affect the females. In addition, the diazepam
      administration during the prenatal, postnatal and pre-postnatal periods decreased
      the numbers of both light and dark granule cells in males, while these two
      granule cell subpopulations were not affected in diazepam treated females. These
      results indicate that perinatal administration of diazepam can alter the sexual
      dimorphism in the accessory olfactory bulb and that the GABAA/benzodiazepine
      receptor complex is involved in the sexual differentiation this part of the
      brain.

PMID- 8156380
TI  - Tonic D2-mediated attenuation of cortical excitation in nucleus accumbens neurons
      recorded in vitro.
AB  - The effects of dopamine D1 and D2 selective drugs on the responses evoked in
      accumbens neurons by stimulation of cortical afferents were studied in an in
      vitro brain slice preparation. The D2-specific antagonist sulpiride (1-10 microM)
      increased, whereas the D2 agonist quinpirole (1-20 microM) occasionally
      attenuated the amplitude of stimulation-evoked EPSPs recorded in accumbens
      neurons. Administration of the D1 agonist SKF 38393 (3-10 microM) or the D1
      antagonist SCH 23390 (10 microM) did not alter the EPSP amplitude, although an
      apparent change in the time course of the EPSP was often observed. In slices
      obtained from dopamine (DA)-depleted animals, sulpiride failed to induce changes
      in the amplitude of the EPSPs, whereas quinpirole produced a highly significant
      suppression of EPSP amplitude that was only occasionally observed in control
      slices. These results indicate that DA modulates the response of accumbens
      neurons to cortico-accumbens fiber stimulation via D2 receptors. Furthermore,
      these D2 receptors appear to be located presynaptically on the cortical afferent
      terminals, since this action of DA was not accompanied by changes in membrane
      potential, input resistance, or time constant, and was not modified by changes in
      the membrane potential. These data provide evidence for a tonic basal level of D2
      receptor stimulation in the accumbens slice preparation.

PMID- 8156381
TI  - Protein kinase C subspecies in hippocampus and striatum of reserpinized rat
      brain.
AB  - Protein kinase C (PKC) (alpha) and (beta) immunoreactivities were determined in
      the cytosolic and particulate fractions of the hippocampus and striatum after
      single and repetitive, intraperitoneal administration of reserpine. Significant
      decrease of PKC(alpha) immunoreactivities was observed in the particulate
      fractions of both striatum and hippocampus. Compared with the alteration of
      PKC(alpha), the decreased immunoreactivity of PKC(beta) was only observed in the
      particulate fraction of the hippocampus, associated with the increase in the
      cytosolic fraction. These findings suggest a novel mechanism regulating the
      distribution of PKC. The topographical selectivity in the present study may
      indicate the importance of the alteration of PKC(beta) in the pathophysiological
      mechanism in Alzheimer's disease.

PMID- 8156382
TI  - Cardiovascular changes elicited by microinjection of glycine or GABA into the
      spinal intermediolateral nucleus in urethane-anesthetized rats.
AB  - Sympathetic preganglionic neurons (SPNs), located in the intermediolateral cell
      column (IML) of the thoracolumbar spinal cord, contribute to the maintenance of
      arterial pressure (AP) and heart rate (HR) within normal limits under different
      physiological conditions. The purpose of this study was to examine the effects of
      microinjecting the putative inhibitory transmitters glycine (GLY) or gamma-amino
      butyric acid (GABA) into functionally identified cardioacceleratory and
      vasoconstrictor IML sites at T1-T3. Rats were anesthetized (1.4 g/kg urethane
      i.p.), paralysed with decamethonium bromide (3.3 mg/kg i.v.) and artificially
      ventilated. Glutamate (GLU) microinjection (10-20 nl, pH = 7.4, 0.15 M in
      phosphate-buffered saline (PBS)) was used to identify 29 vasoconstrictor sites,
      of which 23 were also cardioacceleratory, in the right side of the T2 segment.
      GLY microinjection (10-20 nl, pH = 7.4, 0.5 M in PBS) into these sites resulted
      in significant decreases in both AP (n = 18) and HR (n = 14). The AP and HR
      responses to GLY were brief in duration and were attenuated by the specific GLY
      antagonist strychnine (STR). Microinjection of GABA (10-20 nl, pH = 7.4, 0.15
      0.84 M in PBS, n = 6) and its agonist muscimol (10-20 nl, pH = 7.4, 0.9 mM in
      PBS, n = 6) into GLU-identified sites in the IML caused no changes in AP or HR.
      However, after the application of either GABA or muscimol, the changes in AP or
      HR elicited by GLU were eliminated, suggesting that GABA and muscimol decrease
      the excitability of SPNs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156383
TI  - Differential control of glucoregulatory hormone response and glucose metabolism
      by NMDA and kainate.
AB  - The aim of the present study was to elucidate the effect of kainate and N-methyl
      D-aspartate (NMDA), two different excitatory amino acid (EAA) agonists, on
      glucoregulatory hormone production and whole body glucose metabolism. Rates of
      hepatic glucose production (HGP) and peripheral glucose utilization (GU) were
      assessed in overnight fasted, catheterized, conscious rats using [3-3H]glucose.
      At the highest dose of kainate examined (16 mg/kg), glucose levels increased 97%
      after 1 h; thereafter, glucose fell towards basal values but was still elevated
      25% at the end of the 3 h experiment. This hyperglycemia resulted from a rapid
      increase in HGP that exceeded an increased rate of GU. Both HGP and GU were
      elevated 86% throughout the final 2 h of the experiment. NMDA induced changes in
      glucose flux that were qualitatively similar, yet of smaller magnitude and of
      shorter duration, than those produced by kainate. Kainate-induced increases in
      glucose metabolism were associated with an early transient hyperinsulinemia
      followed by a period of insulinopenia, and sustained increases in the plasma
      concentrations of glucagon, corticosterone, epinephrine and norepinephrine. In
      contrast, sustained increases in glucagon and catecholamines, as well as the late
      hypoinsulinemia were not detected in NMDA-treated rats. Adrenergic blockade
      attenuated the kainate- but not the NMDA-induced increase in glucose metabolism.
      These results indicate that EAA agonists that bind preferentially to different
      receptor subtypes produce qualitatively similar changes in glucose metabolism.
      Whereas the increased HGP in kainate-injected rats was associated with sustained
      elevations in glucagon, catecholamines and corticosterone, NMDA only transiently
      elevated circulating glucocorticoid levels, suggesting a different mechanism of
      action. These data, support the involvement of EAA in various aspects of
      glucoregulation.

PMID- 8156384
TI  - Distribution and steroid dependence of aromatase enzyme immunoreactivity in
      limbic nuclei of the female musk shrew brain.
AB  - In the female musk shrew (Suncus murinus) neural aromatization of testosterone to
      estradiol is critical for the expression of sexual behavior. To localize the
      brain regions capable of aromatization, we used immunocytochemistry to map the
      distribution of aromatase enzyme. Aromatase immunoreactivity (AROM-ir) has a
      discrete distribution primarily limited to the lateral septum (LS), central
      nuclei of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST). In
      these nuclei the intensity of immunoreactivity varies with hormonal status.
      Ovariectomy (OVX) significantly reduces the optical density of AROM-ir neurons in
      all nuclei as compared with brains of normal females. Combined OVX and
      adrenalectomy (ADX) further reduces optical density readings in AROM-ir cells in
      the LS and BST, as compared with readings from the brains of OVX animals. Normal
      and ovariectomized females implanted with testosterone had qualitatively
      equivalent AROM-ir. High levels of aromatase activity have been measured in the
      preoptic area and hypothalamus in a number of mammals, including the musk shrew.
      However, in this experiment AROM-ir was absent in these areas. We present several
      hypotheses to account for this discrepancy between previously reported
      biochemical data and these histological data. In summary, these data suggest that
      limbic nuclei may play a role in the expression of sexual behavior in female musk
      shrews.

PMID- 8156385
TI  - A cholinergic propriospinal innervation of the rat spinal cord.
AB  - Previous work has suggested the presence of a widespread, intrinsic cholinergic
      innervation of the spinal cord. A combination of retrograde axonal tract tracing
      and choline acetyltransferase immunocytochemistry was used to show that there is
      a propriospinal cholinergic innervation of the rat spinal cord that arises from
      short-range projections (spanning up to six spinal segments) of cholinergic
      neurons known as 'central canal' and 'partition' cells.

PMID- 8156386
TI  - Dopamine depletion in nigrostriatal neurons in the genetically diabetic rat.
AB  - Employing tyrosine hydroxylase (TH) immunohistochemistry, we have revealed that
      the enzyme is depleted in nigrostriatal neurons in the genetically diabetic BB
      Wistar (BBWd) rat. A similar, but much less marked reduction in TH
      immunoreactivity occurred in the mesolimbic dopamine system, which arises from
      the ventral tegmental area and terminates in the nucleus accumbens. The
      projection to the olfactory tubercle appeared unaffected. Since the decreased
      levels of dopamine in the mesencephalic dopamine systems could not be restored
      under insulin-controlled conditions, the impairment of dopamine biosynthesis in
      the BBWd rat may be genetically programmed.

PMID- 8156387
TI  - Gender differences in tuberoinfundibular dopaminergic neuronal activity in a
      photoperiodic rodent (Mesocricetus auratus).
AB  - When compared to males, female hamsters showed higher concentrations of
      dihydroxyphenylacetic acid (DOPAC) in the median eminence. This gender difference
      may be related to the higher levels of prolactin seen in females, but it is not
      associated with sex differences in median eminence dopamine or in the number of
      arcuate dopaminergic neurons.

PMID- 8156388
TI  - Postnatal increase of GABA- and PV-IR cells in the cerebral cortex of the lizard
      Podarcis hispanica.
AB  - The number and distribution of GABA- and parvalbumin (PV)-immunoreactive (IR)
      cells have been studied by immunocytochemistry in the cerebral cortex of newborn
      and adult lizards. The distribution of GABA-IR cells as well as that of PV-IR
      cells were similar in newborn and adult lizards, and PV-IR cells were GABA-IR in
      all cases. However, the absolute number of GABA- and PV-IR cells increased
      significantly during development. In addition, the rate of of GABA-IR cells also
      displaying PV immunoreactivity also increased after birth. Moreover, dendrites
      were rarely found to be PV-IR in newborn lizards, whereas they appeared stained
      in a Golgi-like manner in adult animals. These results suggest that the GABAergic
      neuronal population of the cerebral cortex of lizards experiments a significant
      increment in number and neurochemical maturation after birth.

PMID- 8156389
TI  - The human locus coeruleus and anxiogenesis.
AB  - Electrical stimulation of locus coeruleus (LC), via permanently implanted
      electrodes with confirmed localization and effectiveness, did not elicit any
      subjective or behavioral manifestations of anxiety. This is evidence against the
      hypothesis that LC is a mediator of anxiogenesis in man.

PMID- 8156390
TI  - Dopamine receptor density, sensitivity and mRNA levels are altered following self
      administration of cocaine in the rat.
AB  - The effects of cocaine administration and withdrawal on D1 and D2 dopamine
      receptor number, affinity, and mRNA levels were examined in rats trained to self
      administer cocaine for four weeks on a continuous reinforcement schedule. Two
      hours after the last infusion of cocaine there was a decrease in the number and
      agonist sensitivity of dopamine D1 receptors in the anterior forebrain as well as
      in the limbic region. In contrast, there were no discernible changes in dopamine
      D2 receptors in any of the brain regions examined. Examination of dopamine
      receptor gene expression using Northern blot analysis revealed that there was an
      increase in D1 receptor mRNA levels in the forebrain, whereas D1 and D2 receptor
      mRNA levels both were increased in the limbic region. One week following the last
      infusion of cocaine, D1 and D2 receptor mRNA levels had returned to baseline. In
      the limbic region, D1 receptor numbers also had normalized by this time, whereas
      in the forebrain, changes in D1 receptors persisted. These data indicate that
      repeated exposure to cocaine induces regional changes in D1 receptor sensitivity
      and gene expression, suggesting that the D1 dopamine system plays an important
      role in mediating the reinforcing effects of cocaine.

PMID- 8156391
TI  - Central NMDA enhances hepatic glucose output and non-insulin-mediated glucose
      uptake by a nonadrenergic mechanism.
AB  - One of the hallmarks of the stress response is an increased rate of hepatic
      glucose production (HGP) which, in conjunction with the presence of insulin
      resistance, leads to hyperglycemia. Excitatory amino acids (EAA) within the brain
      mediate some of the cardiovascular responses to stress, but their role in the
      hormonal and metabolic alterations is poorly defined. The aim of the present
      study was to determine whether the intracerebroventricular (i.c.v.) injection of
      either N-methyl-D-aspartate (NMDA) or kainate would produce metabolic alterations
      comparable to those observed under stress conditions. An i.c.v. cannula and
      vascular catheters were placed in rats prior to the experiment. After an
      overnight fast, HGP and peripheral glucose utilization (GU) were assessed in
      conscious unrestrained rats using [3-3H]glucose. Arterial glucose levels were
      increased 34% by 15 min after the i.c.v. injection of NMDA (1 microgram) and
      remained elevated throughout the 3-h protocol. The hyperglycemia resulted from an
      early increase in HGP (84%) that exceeded a smaller elevation (66%) in GU. The
      increased glucose flux was associated with sustained insulinopenia (-30%), and
      elevated levels of corticosterone (40-100%) and epinephrine (75-216%). The
      hormonal and glucose metabolic responses were quantitatively similar, although of
      shorter duration, in rats injected with kainate (10 ng). Intravenous adrenergic
      blockade completely prevented the NMDA-induced hyperglycemia. Adrenergic blockade
      blunted the early rise in HGP, so that in this group the NMDA-induced increase in
      HGP was offset by a comparable elevation in GU.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156392
TI  - Effect of dietary vitamin E on lipofuscin accumulation with age in the rat brain.
AB  - We investigated the effect of dietary vitamin E on lipofuscin accumulation with
      age in the hippocampus, the inferior olive and the cerebellum of young (3-5
      months old) middle-aged (12-14 months old) and old (24-26 months old) male
      Sprague-Dawley rats. The rats were fed either a vitamin E-deficient diet, vitamin
      E-supplemented diet or a control diet after reaching four weeks old. We employed
      both quantitative light microscopy using semithin sections and qualitative
      fluorescence microscopy for the analysis of lipofuscin accumulation with age. The
      concentrations of alpha-tocopherol were measured simultaneously in both the
      plasma and the three brain regions investigated. The effect of vitamin E
      deficiency was statistically significant only in the inferior olive of young rats
      and in all the three brain regions of middle-aged rats. The effect of vitamin E
      supplementation was statistically significant in all three brain regions of
      middle-aged rats. There was no statistically significant effect of vitamin E
      deficiency or supplementation on lipofuscin accumulation with age as compared
      with the control rats in all three brain regions of old rats. It was thus
      revealed that dietary vitamin E clearly had a significant effect on lipofuscin
      accumulation with age in the rat brain up until middle age, and that the same
      effect became indistinct in the latter half of their life.

PMID- 8156393
TI  - Effects of nerve growth factor on catalase and glutathione peroxidase in a
      hydrogen peroxide-resistant pheochromocytoma subclone.
AB  - Stepwise selection in increasing H2O2 concentrations was used to obtain a PC12
      cell variant designated HPR. This variant was stably resistant to H2O2 as
      compared with the parental PC12 cell line. HPR cells responded to nerve growth
      factor (NGF) by further enhancing H2O2 resistance. This variant was subcloned by
      limiting dilution to obtain the line referred to as HPR-C, which was stably
      resistant to H2O2 toxicity and retained NGF responses, including morphologic
      changes and further reduction of H2O2 toxicity. When compared with the parental
      PC12 line, the HPR-C subclone did not have higher levels of catalase or
      glutathione peroxidase (GSH Px) activity or mRNA expression (as assessed by PCR
      analysis of cDNA reverse transcribed from total cellular RNA). HPR-C cells
      retained the ability to respond to NGF treatment by increasing catalase and GSH
      Px activity and expression. These data suggest that the protective effects of
      conditioning lesions, unlike those of neurotrophins, are in part independent of
      changes in the activity or expression of antioxidant enzymes.

PMID- 8156394
TI  - Brain catecholamines mediate the delayed reduction in renin release after
      injection of fenfluramine.
AB  - The present studies examined whether brain or peripheral catecholaminergic
      mechanisms mediate the fenfluramine-induced reduction in plasma renin activity
      and concentration. Fenfluramine reduced plasma renin activity and concentration
      to 35% of basal levels in vehicle pretreated rats. This reduction was prevented
      in rats whose central catecholaminergic neurons were destroyed by i.c.v.
      injection of 6-hydroxydopamine (6-OHDA) two weeks prior to the experiment. In
      contrast, the suppressive effects of fenfluramine on plasma renin activity and
      concentration was not altered in rats that were surgically adrenal
      medullectomized and chemically sympathectomized by 6-OHDA. To determine whether
      alpha 2 adrenoceptors mediate the suppressive effects of fenfluramine, rats were
      pretreated with increasing doses of the alpha 2 adrenoceptor antagonist yohimbine
      1 h before the administration of fenfluramine. Although yohimbine alone increased
      plasma renin activity and concentration, it did not prevent the suppressive
      effects of fenfluramine. In conclusion, the data suggest that central, but not
      peripheral catecholamines mediate the suppressive effect of fenfluramine on renin
      secretion. This effect is not mediated by alpha 2 adrenoceptors.

PMID- 8156395
TI  - Cognitive and neuroanatomical effects of triethyltin in developing rats: role of
      age of exposure.
AB  - Long-Evans rat pups were injected i.p. on postnatal day 5 (PND5) or 12 with 0, 3,
      or 5 mg/kg triethyltin sulfate (TET) and then tested on T-maze delayed
      alternation on PND21 or 28. Delayed alternation learning was impaired on PND21
      and 28 in pups given 5 mg/kg TET. Pups given 5 mg/kg TET on PND5 were more
      impaired on delayed alternation than pups given 5 mg/kg TET on PND12. Pups given
      3 mg/kg TET on PND5 or 12 were unimpaired at either age of testing. On the day
      following training, pups were sacrificed for histological assessment employing
      Nissl- or immunohistochemical staining for glial fibrillary acidic protein
      (GFAP), a putative marker of gliosis. Pups given 5 mg/kg TET on PND5 showed
      increases in GFAP immunoreactivity (IR) in subiculum, amygdala, hippocampus,
      piriform cortex, and entorhinal cortex with concomitant decreases in Nissl
      stained cells in these regions. Pups given 5 mg/kg TET on PND12 showed increases
      in GFAP IR in piriform cortex, amygdala and dorsal hippocampus with concomitant
      decreases in Nissl-stained cells in these regions. Exposure to 3 mg/kg TET on
      PND5 and PND12 produced a mild increase in GFAP IR in piriform cortex and
      amygdala but no discernible loss of Nissl-staining in these respective regions.
      TET-induced behavioral deficits appear related to damage of structural correlates
      of the human temporal lobe and not piriform cortical pathology. These results
      demonstrate that the day of exposure greatly influences the magnitude of the
      cognitive deficits and neuropathology associated with exposure to TET. There
      appears to be a critical period during postnatal development for the
      developmental neurotoxicity of this compound.

PMID- 8156396
TI  - Desmethylimipramine, a potent inhibitor of synaptosomal norepinephrine uptake,
      has diverse effects on thyroid hormone processing in rat brain. II. Effect on in
      vivo 5'-deiodination of [125I]thyroxine.
AB  - We have studied the effects of desmethylimipramine (DMI), a tricyclic
      antidepressant, on thyroid hormone (TH) handling in rat brain in an effort to
      discover a pharmacological basis for reported interactions between TH, affective
      disorders and psychotropic drugs. An acute dose of DMI has been used in order to
      determine the primary effects of the drug in brain without perturbations from
      secondary effects. Recently we have reported that a single dose of DMI
      significantly decreases brain uptake of both [125I]thyroxine (T4) and
      [125I]3,3',5-triiodothyronine (T3) across the spectrum of thyroid states from
      hypothyroid (HYPO) to euthyroid (EU) to T4-induced hyperthyroid (HYPER). To
      investigate further the effects of DMI on brain processing of TH, we have
      measured effects of the drug on in vivo rates of T4 to T3 conversion in a series
      of experiments in which DMI (25 mg/kg) was given to HYPO, EU and HYPER male rats
      in conjunction with i.v. [125I]T4. Decreased in vivo conversion ratios (T3/T4
      ratios) suggest that acute DMI treatment causes a significant decrease in 5'
      deiodinase activity in balance of brain (but not cerebellum) in all DMI treated
      rats as compared to their saline treated controls (ANOVA, P < 0.0001). For
      assurance that reduced T3/T4 in DMI treated rat brain is not the result of DMI
      enhancement of 5-deiodination of T3 or T4, the effect of DMI on concentrations of
      labeled I-, rT3, and T2 (3,3'- and 3',5'-) was also observed. In no case was
      there a significant increase in any metabolite in DMI treated rats for any tissue
      studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156397
TI  - mu-Opioid receptors modulate noradrenaline release from the rat hippocampus as
      measured by brain microdialysis.
AB  - The modulation of noradrenaline (NA) release via presynaptic opioid receptors in
      the hippocampus of freely moving rats was studied by the use of brain
      microdialysis. Extracellular levels of NA were estimated by assaying its
      concentrations in the perfusion fluid using high-performance liquid
      chromatography (HPLC) with electrochemical detection (ECD). Spontaneous NA levels
      were reduced by tetrodotoxin (1 microM) co-perfusion and were increased by
      peripheral administration of desipramine (5 and 10 mg/kg, i.p.). Addition of
      potassium (K+, 60 and 120 mM) to the perfusion fluid evoked a concentration
      dependent release of NA. K+ (120 mM)-evoked NA release was markedly reduced by
      removal of calcium (Ca2+) from the perfusion fluid. These results indicate that
      both the spontaneous and the K(+)-evoked NA release measured by the use of brain
      microdialysis coupled with HPLC-ECD can be used as indices of neuronal release
      from the noradrenergic nerve terminals. A mu-opioid receptor agonist, morphine
      (0.01-10 microM), when co-perfused with K+ (120 mM), produced a reduction of K(+)
      evoked NA release in a concentration-dependent manner. Neither co-perfusion with
      a high concentration of [D-Pen2, D-Pen5]-enkephalin (DPDPE) (10 microM), an
      agonist selective for delta-opioid receptors, nor with U-69593 (10 microM), an
      agonist selective for kappa-opioid receptors, modified the K+ (120 mM)-evoked
      release of NA. Morphine-induced (1 microM) inhibition of NA release was blocked
      by a mu-opioid receptor antagonist, naltrexone (3 and 9 mg/kg, i.p). Naltrexone
      by itself did not alter the spontaneous NA levels or the K(+)-evoked NA
      release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156398
TI  - Effects of dizocilpine on autotomy behavior after nerve section in mice.
AB  - The effects of acute administration of dizocilpine (MK-801) at different
      perioperative times on autotomy behavior after sciatic and saphenous nerve
      transection were studied in the mouse. Control mice developed a severe self
      mutilating behavior starting 1-3 days postoperation and reaching a maximum by 11
      days. Mice injected with a single dose of dizocilpine (0.4 mg/kg i.p.) before
      operation, the 1st or 3rd postoperative day autotomized significantly less than
      controls. An 1-wk treatment with the same dose once a day did not show further
      benefit. A single administration of dizocilpine the 5th day after surgery
      slightly halted further progression of autotomy. Dizocilpine did not have any
      deleterious effect on normal peripheral nerve function. These results suggest
      that NMDA receptor blockade prevents development of hyperalgesia and neuropathic
      pain after peripheral nerve injuries but only when it is administered before or
      during the first 3 days after injury.

PMID- 8156399
TI  - Opposite changes in the mesolimbic dopamine metabolism in the nerve terminal and
      cell body sites induced by locally infused baclofen in the rat.
AB  - Infusion of baclofen (10(-4) M, 1 h) into the ventral tegmental area (VTA), the
      cell body site of mesolimbic dopamine (DA) neuron system in conscious rats,
      caused a decrease in both axonal and somatodendritic DA release in this neuron
      system, when monitored by in vivo microdialysis using two probes simultaneously
      placed in both the NAC and the VTA. Levels of the metabolite of DA, 3,4
      dihydroxyphenylacetic acid (DOPAC) in the VTA decreased significantly in a
      similar manner following infused baclofen into the VTA, however, a pronounced
      increase in DOPAC outflow was observed in dialysates from the NAC. This
      dissociated changes in DA metabolism observed in the NAC may possibly be derived
      from regulatory mechanisms via an autoreceptor located in the DA nerve terminals.

PMID- 8156400
TI  - REM sleep-suppressing effects of atropine in cats vary with environmental
      temperature.
AB  - Because the occurrence of rapid eye movement (REM) sleep is critically dependent
      upon an animal's thermal balance, acute pharmacological treatments may effect REM
      sleep through effects on thermoregulation. We describe how manipulating ambient
      temperature (T(a)) alters the REM sleep-suppressing effects of systemically
      administered atropine, a muscarinic receptor antagonist, in adult cats. At a T(a)
      of 23 degrees C , atropine (0.5 mg/kg) produced a significant reduction in REM
      sleep time that persisted for about 8 h of a 16 h recording period. Hypothalamic
      temperature fell below control levels for about 4 h following atropine. At a T(a)
      of 30 degrees C, the same dose of atropinehad no significant effect on REM sleep
      time, or hypothalamic temperature. These findings indicate the importance of
      considering the possible role of thermoregulation in drug-induced effects on REM
      sleep.

PMID- 8156401
TI  - Traumatic injury induces interleukin-6 production by human astrocytes.
AB  - The brain is being evaluated as a de novo source of cytokines. Because recent
      evidence indicates that interleukin-6 (IL-6) may influence blood-brain barrier
      function and vascular permeability, we have sought to determine whether
      mechanical injury can directly induce in situ cerebral IL-6 production. Adult
      human astrocyte cultures were subjected to mechanical injury by the in vitro
      method of fluid percussion barotrauma, developed in our laboratory. Serial
      supernatant samples were collected for 8 h and evaluated for IL-6 activity using
      a proliferation assay employing the dependent B cell hybridoma cell line, B9. At
      optimum injury, the IL-6 level became significantly (P < 0.0001, analysis of
      variance) elevated from baseline 2 h after trauma and continued to increase over
      the observation period. Our study shows that following mechanical injury human
      astrocytes produce IL-6, which may contribute to post-traumatic cerebrovascular
      dysfunction. Elucidating the precise role of intracerebral cytokines is essential
      to our understanding of the mechanism responsible for post-traumatic
      cerebrovascular dysfunction.

PMID- 8156402
TI  - Acute gentamicin ototoxicity in cochlear outer hair cells of the guinea pig.
AB  - The acute effects of the aminoglycoside antibiotics gentamicin on isolated
      cochlear outer hair cells (OHC) was investigated by whole-cell patch-clamp and
      measurements of the intracellular potassium level by means of the potassium
      sensitive dye PBFI. In addition, the accompanying length changes of OHC are
      described. It could be shown that gentamicin at different concentrations
      reversibly induces a hyperpolarization by about 5-10 mV, potassium outflow from
      the cytoplasm (by about 22 mM) and a cellular elongation (by about 10%). It is
      suggested that these effects are the result of an interaction between gentamicin
      and the cochlear transduction channels in OHC as suggested earlier. These acute
      effects are distinctly different from the chronic gentamicin effects which are
      based on the metabolization of the antibiotics to cause the death of the OHC by
      interaction with the phosphoinositide signalling cascade.

PMID- 8156403
TI  - Administration of amyloid beta-peptides into the medial septum of rats decreases
      acetylcholine release from hippocampus in vivo.
AB  - The septum of male Wistar rats was injected with synthetic beta-amyloid
      fragments, beta 12-28, beta 25-35 and beta 1-40, and hippocampal acetylcholine
      (ACh) release was evaluated by transversal microdialysis. A marked decrease in
      basal and K(+)-evoked ACh release was found 7 or 21 days after injection of 5
      nmol of beta 12-28 and beta 25-35, or 3 nmol of beta 1-40, respectively. These
      data indicate that septal injection of beta-amyloid peptides causes hypofunction
      of the septo-hippocampal cholinergic system.

PMID- 8156404
TI  - Modified cardiovascular sensitivity of the area postrema to vasopressin in
      spontaneously hypertensive rats.
AB  - Vasopressin has been shown to act at the area postrema to increase the
      sensitivity of the baroreceptor reflex. We have previously demonstrated that
      microinjection of vasopressin into the area postrema of Sprague-Dawley rats
      elicits pressor effects. We report here that vasopressin microinjection into the
      area postrema of spontaneously hypertensive rats is without effect on blood
      pressure, whereas microinjection into age-matched Wistar-Kyoto controls results
      in significant increases in blood pressure at 50 and 100 pg. These results
      suggest an altered sensitivity of the area postrema to vasopressin in this
      genetic model of hypertension.

PMID- 8156405
TI  - Identification of nocifensor reflex-related neurons in the rostroventromedial
      medulla of decerebrated rats.
AB  - Extracellular single unit recordings were made from neurons in the
      rostroventromedial medulla of decerebrated rats. The previously described 'on
      cell' and 'off-cell' classes were found in this preparation, and this
      classification, which is based on tail flick-related changes in activity, was not
      altered by the introduction or removal of halothane anesthesia. It is therefore
      evident that the identifying physiological properties of on- and off-cells are
      not dependent on the presence of anesthesia in decerebrate rats, or on brain
      structures rostral to the inferior colliculi.

PMID- 8156406
TI  - Endogenous opioids and sexual motivation and performance during the light phase
      of the diurnal cycle.
AB  - The sexual motivation and performance of sexually experienced male rats were
      tested during the light phase of the diurnal cycle after treatment with saline or
      1 mg.kg-1 naloxone in a bilevel testing box. The sexual motivation during the
      light phase, as assessed by the increase in anticipatory level changes prior to
      introduction of a receptive female on subsequent weekly sessions, was comparable
      to that during the dark phase. Opioid blockade reduced the increase of level
      changes, suggesting that endogenous opioids are involved in sexual motivation.
      The sexual performance was impaired during the light phase. Naloxone treatment
      failed to affect the sexual performance, other than that the post ejaculatory
      refractory period was increased. This increased latency to re-initiate copulation
      may be an expression of the reduced sexual motivation. It is concluded that
      endogenous opioids are not involved in the regulation of the impaired sexual
      performance during the light phase of the diurnal cycle. In contrast, the sexual
      motivation, which displays no marked diurnal variation, may be stimulated by
      endogenous opioids.

PMID- 8156407
TI  - Neuropeptide Y attenuates satiety: evidence from a detailed analysis of patterns
      ingestion.
AB  - Centrally injected neuropeptide Y (NPY) is a potent stimulant of ingestive
      behavior capable of augmenting both food and fluid intake in fully satiated
      animals. To gain further insight into NPY's mechanism of action, we recorded
      patterns of licking behavior in rats drinking sweetened condensed milk solutions
      immediately after lateral ventricular injection of NPY (10 micrograms) or
      vehicle. In a separate study, we examined licking patterns after 23 h food
      deprivation (FD) that produced approximately the same total intake as NPY.
      Consistent with previous reports, we found NPY stimulated intake by increasing
      total ingestion time and total volume consumed during a 1-h test. Although NPY
      increased the number of bouts of licking and shortened pauses between bouts, it
      also decreased mean bout size, bout duration and within-bout lick rate (local
      rate). It had no significant effect on start latency or lick efficiency
      (licks/ml). Further analyses revealed that NPY attenuated satiety (reduced slope
      of lick-rate functions with session time) but had no significant effect on the
      beginning lick rate, a measure related to orosensory excitation. In contrast to
      NPY, FD increased both the beginning lick rate and individual bout size without
      changing either the mean number of bouts or the pause between bouts. In general,
      NPY stimulated an intermittent pattern of licking and delayed satiation whereas
      FD increased the initial rate of licking and the size of individual bouts without
      changing the basic licking pattern. The increase in initial lick rate suggests
      that FD, unlike NPY, enhances orosensory stimulation. These data compliment
      previous results showing that NPY increases the motivation to eat.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156408
TI  - Effect of diabetes mellitus on response of the basilar artery to activation of
      ATP-sensitive potassium channels.
AB  - Our goal was to determine whether responses of the basilar artery to activation
      of ATP-sensitive potassium channels are altered during diabetes mellitus. We
      measured changes in diameter of the basilar artery in vivo in non-diabetic and
      diabetic rats (streptozotocin; 50-60 mg/kg i.p.) in response to activation of ATP
      sensitive potassium channels using aprikalim (RP 52891) and levcromakalim (BRL
      38227). Aprikalim (1.0 microM) dilated the basilar artery in non-diabetic rats by
      27 +/- 6%, but by only 11 +/- 3% in diabetic rats (means +/- S.E.; P < 0.05).
      Levcromakalim (1.0 microM) dilated the basilar artery in non-diabetic rats by 45
      +/- 11%, but by only 20 +/- 5% in diabetic rats (P < 0.05). Nitroglycerin (1.0
      microM) dilated the basilar artery by 20 +/- 5% in non-diabetic rats and 17 +/-
      2% in diabetic rats (P > 0.05). Thus, impaired dilatation of pial arterioles in
      diabetic rats in response to aprikalim and levcromakalim is not related to a non
      specific effect of diabetes mellitus on vasodilatation. The findings of the
      present study suggest that ATP-sensitive potassium channels are functional in the
      rat basilar artery in vivo and are altered during diabetes mellitus.

PMID- 8156409
TI  - Neurotensin-like immunoreactivity in locust supraesophageal ganglion and optic
      lobes.
AB  - A substance immunoreactive to antibodies directed against bovine neurotensin (NT)
      was localized in neurons in the supraesophageal ganglion (SEG) and optic lobes of
      larval and adult Locusta migratoria L. Two large somata were located in the
      caudal cortex, ventral to the calyces and symmetrical to the median of the SEG.
      Four smaller somata also in the caudal cortex were located as two symmetrical
      pairs at the level of the central body. These somata formed a diffuse network of
      varicose fibers from the superior lateral to the ventro-lateral protocerebrum
      between the pedunculi and frontal cortical region. Some fibers crossed the median
      to the contralateral sides of the SEG. Another pair of immunoreactive somata
      whose terminating processes remained unclear was found at the level of the
      antennal lobes. Intrinsic networks of fibers were labeled in the accessory
      medulla and in layer 4/5 of the medulla. These fibers originated from 8-10 small
      somata near the dorso-frontal rim of the medulla. All larval stages contained
      these NT-like immunoreactive structures. Results from isoelectric focusing and
      press-blot analysis of SEG homogenates, synthetic neurotensin and neurotensin
      fragments indicate that this substance is similar to bovine neurotensin(1-13).

PMID- 8156410
TI  - Aldosterone modulates glucocorticoid receptor binding in hippocampal cell
      cultures via the mineralocorticoid receptor.
AB  - The regulation of corticosteroid receptor expression in the rat brain by adrenal
      steroids remains controversial. The results of in vivo studies [Brinton and
      McEwen, 1988; Luttge et al., 1989] suggest that activation of type I receptors
      can modulate both mineralocorticoid (MR; type I) and glucocorticoid (GR; type II)
      receptor binding in selected brain regions. The present study utilized primary
      hippocampal cell cultures from rats sacrificed at E19-20 days of gestation to
      examine the effects of RU 28362, corticosterone (CORT) and aldosterone (ALDO) on
      GR binding ([3H]dexamethasone +/- RU 28362). Four days of exposure to 10 nM RU
      28362, a highly selective GR agonist, resulted in a robust (approximately 70%)
      decrease in GR binding. Similar exposure to 10 nM of either CORT or ALDO also
      produced a significant (50-55%) decrease in GR binding capacity. Scatchard
      analyses confirmed that the diminished GR binding capacity in response to ALDO
      was due to a decrease in total number of binding sites (Bmax for Control = 112 +/
      25 fmol/mg vs. ALDO = 48 +/- 12 fmol/mg) with no significant change in the
      affinity constant. The calculated EC50 from the ALDO concentration response curve
      was 3.5 nM. Competition studies demonstrated that such low nM concentrations of
      ALDO were unable to displace specific [3H]dexamethasone +/- RU 28362 binding.
      Spironolactone, a highly specific MR antagonist, inhibited the ALDO-induced down
      regulation of GR binding. These findings support the hypothesis that MR
      activation can modulate GR binding in hippocampal cells.

PMID- 8156411
TI  - Development of frequency-selective domains in inferior colliculus of normal and
      neonatally noise-exposed rats.
AB  - Topographic patterns of pure-tone responses in inferior colliculus (IC) of Wistar
      rats were mapped using immunohistochemical staining for the nuclear protein Fos,
      the translation product of the c-fos proto-oncogene. Patterns were compared in
      ICs of immature and mature rats and in mature rats which experienced auditory
      deprivation beginning on day 14, an age near the developmental onset of hearing.
      Neonatal hearing losses, caused here by exposure to potentially deafening noise,
      are known to result in audiogenic seizure susceptibility in neonatal rats. These
      seizures can be triggered only by high-frequency stimuli and are believed to be
      initiated in IC. Thus, it seemed possible that susceptibility might depend on
      derangements of topographic frequency representation due to neonatal auditory
      deprivation. The band-like frequency-response domains, characteristic of adult
      IC, were found to be poorly differentiated in ICs of immature rats. On day 12,
      only lower-frequency stimuli induced discrete bands of Fos immunoreactivity while
      responses to higher frequencies remained exceptionally diffuse within ventral
      portions of IC. Only after day 24 did responses to the highest frequencies also
      appear mature. Furthermore, most significantly, adult rats which were transiently
      deafened on day 14, retained the more voluminous response patterns which were
      characteristic of immature IC. Because frequency selectivity in cochlea also
      develops by a low-to-high frequency sequence, results are consistent with a
      hypothesis that topographic organization arises in IC by an activity-dependent
      process. Whereas neonatal noise exposure also conferred audiogenic seizure
      susceptibility, it appears the arrest of tonotopic organization of IC is the
      probable basis of this reflex epilepsy.

PMID- 8156412
TI  - Selective blockade of different brain stem muscarinic receptor subtypes: effects
      on the sleep-wake cycle.
AB  - Changes induced in the sleep-wake cycle by pontine microinjections of muscarinic
      antagonists were studied in freely moving rats, instrumented for chronic
      polygraphic recordings. Pirenzepine (PIR), methoctramine (MET) and p-fluoro
      hexahydro-siladifenidol (p-F-HHSiD), which are highly selective M1, M2 and M3
      antagonists, respectively, were dissolved in 0.1 microliter of sterile isotonic
      saline (0.2 microliter of distilled water for p-F-HHSiD) and injected into the
      pontine reticular nucleus, where the administration of 0.5 microgram carbachol (a
      mixed muscarinic agonist) induced a 52% increase in the amount of desynchronized
      sleep (DS) over a 6 h recording period. The blockade of M2 receptors was shown to
      (i) antagonize DS, by increasing its latency and decreasing its percentage, (ii)
      decrease slow wave sleep, and (iii) enhance wakefulness. These effects were dose
      dependent. No changes in the sleep-wake cycle were observed following
      microinjection of M1 or M3 antagonists. The results support the hypothesis that
      at the brain stem level only M2 receptors are involved in sleep mechanisms and,
      particularly, in the generation and maintenance of DS.

PMID- 8156413
TI  - Fibrous and protoplasmic astrocytes express GABAA receptors that differ in
      benzodiazepine pharmacology.
AB  - Astrocytes cultured from spinal cord contain two morphologically distinguishable
      types of astrocytes: fibrous and protoplasmic cells. Both astrocyte subtypes, in
      culture, are able to express GABAA receptors, and their activation results in
      inward currents at the resting potential. Using patch-clamp electrophysiology we
      characterized their basic receptor pharmacology and compared it to spinal cord
      neurons that were also present in small numbers in these cultures. As in neuronal
      GABAA receptors, the local anesthetic pentobarbital effectively potentiated GABA
      induced currents in both astrocyte subtypes. Similarly, the benzodiazepine
      diazepam, on average doubled GABA-induced currents in both astrocytes subtypes.
      In contrast to these effects that were similar in both astrocytes types and
      similar to spinal cord neurons, the response to the convulsant methyl-4-ethyl-6,7
      dimethoxy-beta-carboline-3-carboxylate (DMCM), which is an inverse benzodiazepine
      agonist differs between astrocyte subtypes. DMCM reduced GABA-induced currents by
      about 50% in fibrous astrocytes as we also observed with spinal cord neurons. In
      contrast, DMCM increased GABA currents in protoplasmic astrocytes by up to 150%,
      an effect never observed in neurons. DMCM potentiations of GABA currents have
      recently been attributed to differences in receptor subunit composition. Our
      results thus indicate that subtypes of astrocytes express GABAA receptors that
      differ pharmacologically and likely differ also in subunit composition.

PMID- 8156414
TI  - Dystrophic dendrites induced in cultured Purkinje cells by exposure to
      vinblastine.
AB  - Organotypic cerebellar cultures were exposed to the mitotic spindle inhibitor,
      vinblastine, and examined by light and electron microscopy, and
      electrophysiologically. Purkinje cells in exposed cultures had stunted, varicose
      dendrites when observed in preparations reacted with antibody to
      nonphosphorylated neurofilament protein. Ultrastructurally, microtubules were
      selectively reduced in Purkinje cell dendrites, which contained disarrayed excess
      smooth endoplasmic reticulum, but no large accumulations of densely packed
      neurofilaments. Spontaneous cortical discharges were initially increased in
      vinblastine treated cultures and then ceased, at which time the cultures became
      unresponsive to electrical stimulation. The vinblastine-induced changes were
      attributed to impaired intracellular transport secondary to disruption of
      Purkinje cell dendritic microtubules.

PMID- 8156415
TI  - Immunohistochemical and in situ hybridization study of an insulin-like substance
      in fetal neuron cell cultures.
AB  - We studied the ability of fetal neuron cell cultures from different rabbit fetal
      brain gestational ages to produce and secrete an insulin-like substance (ILS).
      Neurons from 22-day gestation were incubated in serum-containing medium or
      insulin-free/serum-free medium, and 18-day gestation fetal rabbit neurons were
      also incubated in serum-free/insulin containing medium and serum-containing
      medium. The 22-day cultures survived in the serum-containing medium and the
      insulin-free/serum-free medium. The 18-day cultures died when incubated in the
      insulin-free/serum-free or serum-free/insulin-containing medium, but survived
      when incubated in serum-containing medium. Using immunohistochemical and in situ
      hybridization techniques, ILS and insulin-like mRNA were demonstrated within the
      22-day cultures incubated in all media compositions, but not within the 18-day
      cultures incubated in the serum-containing medium. Ultrastructural studies of the
      22-day cultures demonstrated an ILS in the endoplasmic reticulum, Golgi and
      cytoplasm. Northern blots showed the presence of an insulin-like mRNA within the
      22-day gestation neuron cell cultures. Insulin receptor was present in the 22-day
      cultures, but was absent in the 18-day cultures. In addition, we characterized
      the ILS from the 22-day cultures incubated in the insulin-free/serum-free medium
      employing high-performance liquid chromatography (HPLC), radioimmunoassay and
      Western blots. Analysis by HPLC and Western blots demonstrated the presence of an
      ILS in the extract. We have shown that while 22-day fetal neuron cultures produce
      and secrete an insulin-like substance indistinguishable from authentic insulin,
      neuron cell cultures from early brain development do not express this capability.

PMID- 8156416
TI  - Histamine does not play an essential role in electrocortical activation during
      waking behavior.
AB  - Intraperitoneal injection of alpha-fluoromethylhistidine (alpha-FMH; 200 mg/kg),
      a specific inhibitor of histidine decarboxylase produced a severe depletion of
      neocortical and hippocampal histamine 3 h later as determined by a radioenzymatic
      assay. This treatment had no obvious effect on either low voltage fast activity
      (LVFA) in the neocortex or on rhythmical slow activity (RSA) in the hippocampus
      during an 8 h recording period during the rats' light cycle. Scopolamine
      sensitive LVFA, scopolamine-resistant LVFA and scopolamine-resistant hippocampal
      RSA all appeared unaffected. This suggests that any contribution histamine makes
      to electrocortical activation is probably indirect, acting via other transmitter
      systems.

PMID- 8156417
TI  - Effects of sex-linked imperfect albinism in the chicken (sal-c) on plasma
      luteinising hormone concentrations and early egg production.
AB  - 1. When measured before and after the onset of darkness, plasma LH concentrations
      in 40-day-old sex-linked albino pullets (sal-c) were slightly lower than those of
      nonalbinos (s+). 2. This finding prompted an experiment in which plasma LH
      concentrations were measured between 12 and 33 weeks of age when daylength was
      increased at 15 or 21 weeks. Egg production of the early and late maturing albino
      hens was measured. 3. Plasma LH concentrations overall and at 17 weeks were lower
      for albinos than for nonalbinos. In the early maturing group egg production of
      albinos was higher than that of nonalbinos. 4. Results suggest that increased egg
      production of albinos is not the direct result differences in plasma LH
      concentrations but may be a consequence of differences in the control of LH
      secretion.

PMID- 8156418
TI  - Effect of dietary contents of cholecalciferol, 1 alpha,25
      dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol on blood
      concentrations of 25-hydroxycholecalciferol, 1 alpha,25-dihydroxycholecalciferol,
      total calcium and eggshell quality.
AB  - 1. Withdrawal of cholecalciferol (D3) supplement from a layers diet drastically
      reduced blood 25-hydroxycholecalciferol (25-OH-D3), 1 alpha,25
      dihydroxycholecalciferol (calcitriol) and egg specific gravity (SG) within two
      weeks, followed by a decrease in blood total calcium (Ca). 2. Doubling the D3
      supplement in the control diet (27.5 micrograms or 1100 IU/kg) almost linearly
      increased the circulating concentration of 25-OH-D3 without raising the
      concentration of calcitriol, Ca, or egg SG. 3. Replacing D3 by the optimal
      concentration of calcitriol (5 micrograms/kg diet) improved egg SG after 21 weeks
      of treatment without increasing blood calcitriol or total Ca. 4. By itself, 24,25
      dihydroxycholecalciferol [24,25-(OH)2D3] was unable to maintain normal blood
      levels of calcitriol, Ca or egg SG and, when added together with calcitriol in
      the diet, tended to elevate blood Ca but suppress the beneficial effect of
      calcitriol on shell quality, with little or no effect on blood calcitriol.

PMID- 8156419
TI  - Interaction of thyroxine and testosterone in stimulating muscle protein breakdown
      in female broiler chickens.
AB  - 1. The effects of thyroxine (T4), testosterone propionate (TP) and a combination
      of hormone treatments on growth and the rates of muscle protein breakdown
      estimated by Ntau-methylhistidine excretion were studied. 2. Broiler chickens
      aged from 15 d to 27 d were used; T4 and TP were mixed in the basal diet at
      concentrations of 1.2 and 20 mg/kg respectively. 3. Although growth was not
      altered significantly by any treatment, the rate of muscle protein breakdown was
      significantly increased about 2-fold by the combined treatment, but not by
      treatment with T4 or TP alone.

PMID- 8156420
TI  - Effects of endotoxin, interleukin-1 beta and prostaglandin injections on fever
      response in broilers.
AB  - 1. The effect of endotoxin, interleukin-1 beta and prostaglandin on fever
      response was studied in 80 broilers (Hubbard strain). Endotoxin (E. coli, LPS)
      was injected i.v. (1.5 micrograms/kg) and icv (1.5 micrograms/bird); interleukin
      1 (human recombinant IL-1 beta, 80 pg/bird) and prostaglandin E2 (5
      micrograms/bird) were injected icv. Indomethacin (10 mg/kg, i.v.) pretreatment
      was also used before i.v. endotoxin injection. 2. The results showed that
      indomethacin was able to block the fever response induced by i.v. endotoxin
      injection, and IL-1 beta and PGE2 were both effective in producing fever when
      injected icv. These data suggest a prostaglandin-mediated fever response by
      broilers, and also a strong evidence of the involvement of endogenous pyrogen
      (interleukin-1) in fever response in birds.

PMID- 8156421
TI  - Protein synthesis measured in the whole body of chick embryos cultured in vitro.
AB  - 1. Whole body protein synthesis was measured in chick embryos cultured in vitro.
      On day 7 of incubation chick embryos were cultured for 60 min in synthetic serum
      free medium containing 4-[3H]phenylalanine. Specific radioactivities in free and
      protein-bound phenylalanine in the whole embryo were measured, starting 2 min
      after commencement of the culture process. 2. The values for fractional synthesis
      rate (FSR) estimated in vitro at 20, 30, 45 and 60 min during the embryo culture
      agreed well, ranging from 35 to 40%/d, suggesting that the method would serve as
      a useful model for studying the effect of growth promoters in chick embryos. 3.
      Bovine insulin in the synthetic medium did not affect FSR of protein in chick
      embryos cultured in vitro.

PMID- 8156422
TI  - Nesting, dust bathing and perching by laying hens in cages: effects of design on
      behaviour and welfare.
AB  - 1. Laying hens (192 ISA Brown medium hybrids) were housed from 18 to 72 weeks as
      groups of 4 in conventional or experimental cages. The main area of all cages
      provided 675 cm2/hen. All experimental cages had perches, dust baths and nest
      boxes, which were of three types: litter (L), artificial turf (A) or plastic
      rollaway (P). These facilities provided an additional 375 to 480 cm2/hen. The
      nest boxes and dust baths occupied either high or low positions. Behaviour,
      physical condition and production of the birds were regularly recorded. 2.
      Mortality was low (1.6% overall) and egg production very good in all treatments.
      The proportion of cracked and dirty eggs was slightly (but not significantly)
      higher in the experimental cages. In the experimental cages 90% of eggs were laid
      overall in the nest boxes and 3% in the dust baths. The proportion laid in the
      nest boxes was lower early in the laying cycle and increased with time, reaching
      99% in A. 3. The facilities were heavily used. Birds spent about 25% of day time
      on the perches and 10-15% in or near the nest box and dust bath. At night, the
      majority of birds (90 to 94%) roosted on perches, but most of the remainder were
      on the lips of the nest box or dust bath, fouling the interiors. 4. Pre-laying
      behaviour was much more settled in the experimental cages (45 min spent in the
      eventual laying position) than in the conventional ones (20 min) and total
      duration varied from 68 min in A to 87 min in P. The number of nest entries
      varied from 3.0 (A and P) to 4.3 (L); disturbance to sitting birds was
      correspondingly greater in L. 5. Dust bathing in the experimental cages generally
      took place during the afternoon in a single bout of about 5 min duration, whereas
      in the conventional cages it was brief and fragmented (3 bouts of 10 s each). The
      dust bath was also used for foraging behaviour (pecking and scratching). The
      treatments with small dust baths (A and P) caused problems for the birds. 6.
      Feather, foot and claw damage all tended to be less in the experimental than in
      the conventional cages, though only in the last case was the difference
      significant. Keel bone depressions appeared to be associated with perches; they
      were present in 43% of hens in the experimental cages but only 4% in conventional
      cages.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8156423
TI  - Optimum size of feeder grids in relation to the welfare of broiler breeder
      females fed on a separate sex basis.
AB  - 1. The rate of eating food was studied in two experiments to assess the
      relationship between head width and size of feeder grids in broiler breeder
      females. 2. The optimum grid size for food intake was 4 mm wider than head width.
      3. Physical injury should be avoided if the grid aperture is 2 mm wider than the
      maximum head width in the flock measured at the posterior edge of the mandibles.
      4. The rate of eating was decreased in all grid sizes examined compared to
      feeders without grids but the importance of this observation for the welfare of
      broiler breeders is not clear.

PMID- 8156424
TI  - Influence of quantity of litter on nest box selection and nesting behaviour of
      domestic hens.
AB  - 1. Twenty two hens (Gallus gallus domesticus) were given a free choice, for egg
      laying, between 4 nest boxes containing different quantities of wood shavings
      (litter): 3180 cm3 (large), 1060 cm3 (medium), 350 cm3 (small) and none (zero).
      2. There was considerable individual variation in the quantity of litter selected
      for egg laying, but 17 hens laid 50% or more of their eggs in a single litter
      quantity. Hens selected the large quantity in preference to the small and zero.
      More searching, nest selection and nesting behaviours tended to be directed to
      the boxes with the largest quantities and also to the quantities that the hens
      finally selected for egg laying. 3. In a second experiment, the hens from
      experiment 1 which showed a preference for litter, and a further 22 naive hens
      were given a choice of three nest boxes containing no litter and one containing
      one of 6 quantities. Over 30 trials there were 5 replicates using each of the
      three quantities used in experiment 1 plus 115 cm3, 40 cm3 and 10 cm3. 4. There
      was a wide range in the proportion of trials in which hens selected litter; for
      experienced hens the range was 0.43 to 0.97, but only two naive hens were within
      this range, all others being between 0 and 0.43. 5. The pattern of choosing
      litter quantities was comparable but at different levels of preference in
      experienced and naive hens and a contour map was derived enabling predictions to
      be made of the probability of a particular quantity being chosen. 6. The
      variability of individual responses suggest that no single type of nest box
      system can cater for the requirements of all hens.

PMID- 8156425
TI  - Influence of sequence length on the response to ahemeral lighting late in lay.
AB  - 1. An experiment is described in which 96 individually-caged SCWL hens in two
      rooms were used to investigate the response to changing to a 28-h cycle using a
      reverse treatment design. 2. The application of the 28-h cycle did not affect
      mean rate of lay but increased mean egg weight and egg output. 3. Grouping the
      birds according to their preliminary sequence length yielded an interesting
      outcome. In both rooms, birds with short sequences (< or = 6 eggs) produced
      significantly more eggs under the 28-h cycle, while those with long sequences (>
      6 eggs) produced marginally fewer eggs. The same trend was also evident with egg
      output. 4. Changing from 24-h to 28-h increased yolk and albumen weights as well
      as shell quality. However, relative to egg weight, no measurable effect was
      detected due to light cycle, age or sequence length on yolk and albumen weights.
      5. The paper provides new evidence suggesting that long ahemeral cycles could be
      used to improve egg production as well as shell thickness in flocks with modest
      rates of lay.

PMID- 8156426
TI  - Genotypic differences in speed and magnitude of response to ahemeral lighting.
AB  - 1. The paper compares between three genetically different lines in their egg
      weight and shell thickness response to a 28-h cycle. 2. The response in shell
      thickness to ahemeral lighting was more rapid (2.2 d) than for egg weight (4.2
      d). 3. Differences between genotypes were evident in both the speed and magnitude
      of response. 4. Overall, egg weight and shell thickness on the 28-h cycle were 7%
      and 8% greater than on 24 h. 5. The allometric increase indicates that the
      increase in shell weight was on average 14% more than the increase in egg weight.

PMID- 8156427
TI  - Mechanics of standing in birds: functional explanation of lameness problems in
      giant turkeys.
AB  - 1. The parameters used for the mechanics of standing in birds are defined and
      compared for two strains of turkeys, a giant, broad-breasted strain (up to 40
      kg), the result of artificial selection, and a traditional, smaller bird (9 kg),
      in order to show whether the mechanics of standing are modified by selection. 2.
      Using a geometrical similarity hypothesis, it was found that, although the
      locomotor apparatus of both strains are similar, the stresses on the pelvic
      muscles of broad-breasted turkeys are increased. This is induced by the anterior
      position of the centres of gravity of their trunks, the result of selected
      pectoral hypertrophy. 3. The modification to the mechanics of standing may be
      related to the increase in locomotor disease in strains of giant turkeys.

PMID- 8156428
TI  - Variation among individual White-Leghorn hens in the concentration of minerals in
      the albumen and yolk content of their eggs.
AB  - 1. The mineral composition of the albumen and yolk was determined in several eggs
      from each of a number of individual hens from the same White-Leghorn strain. X
      ray fluorescent spectrometry was used to undertake two independent series of
      analyses. A total of 8 minerals (calcium, chlorine, iron, magnesium, phosphorus,
      potassium, sodium, sulphur) were included in the analyses of the yolk and the
      same minerals, but excluding iron (which is present in only small amounts), in
      the albumen. 2. There was considerable variation between individuals in the
      mineral concentration in their eggs (coefficients of variation ranged between
      3.8% for sodium to 19.9% for calcium in the albumen, and between 4.3% for
      phosphorus to 11.8% for iron in the yolk). 3. At the same time, the moderately
      high repeatability of mineral concentration (t = 0.4-0.6) in successive eggs from
      the same hen for several of the minerals analysed is indicative of some positive
      control by the hen of the mineral composition of her eggs. 4. There was a highly
      significant correlation (P < or = 0.001) between the mean concentration of
      potassium in the albumen and the hatchability of the eggs, supporting the claim
      that a deficiency of potassium in the egg could be the basis of some failures in
      hatchability. 5. The study also revealed variation among individual birds in the
      concentration of iron in the yolk which was negatively correlated (P < or = 0.01)
      with hatchability. No clear basis could be suggested for this variation among
      individual birds.

PMID- 8156429
TI  - Effects of storage conditions on hatchability of chicken eggs in a warm climate.
AB  - 1. A total of 3792 eggs from AF Bosbek layer parents were used to determine the
      effect of storage time on the hatchability of eggs kept either small end up (SEU)
      or small end down (SED). 2. These eggs were stored at room temperature (27
      degrees C-31 degrees C) or in an air-conditioned room (20 degrees C-23 degrees
      C), for two, three, six or seven days and incubated in four replicate hatches. 3.
      Eggs kept SEU improved hatchability even for short-term storage when temperatures
      were high. 4. Simple air-conditioning can reduce the temperature sufficiently for
      the viability of the embryo to be preserved for up to a week.

PMID- 8156430
TI  - Increment of egg weight with hen age in various commercial avian species.
AB  - 1. The present study indicates that a common biological pattern exists for egg
      weight increase with hen age for the various commercial avian species, breeds and
      strains at their first laying cycle. Therefore, one common equation can be used
      for the estimation of egg weight increase. 2. The parameters estimated for this
      equation are based on (a) egg weights in terms of percentage of seasonal mean egg
      weight, and (b) age as percentage of maximum age of the hen. Therefore, if the
      season's mean egg weight is known for any species, breed or strain, the increase
      in egg weight can be easily predicted for the whole season, or for any particular
      hen age. For early prediction, egg weight expressed as a percentage of initial
      egg weight can be used, although such prediction will be somewhat less accurate.
      3. The use of egg weight as a percentage of seasonal mean egg weight, and age as
      a percentage of maximum age, was found to overcome the differences between
      strains, breeds and even species, by applying the same denominators for egg
      weights and periods of lay. 4. At each point of hen age (mean egg weight), the
      egg weight grades can be easily estimated by employing the computerised Burr's
      (1967) equation. These values showed excellent fit with extensive field data,
      provided that only normal eggs and those originating from a single flock and from
      no more than two weeks of collection are counted.

PMID- 8156431
TI  - Different growth rates of male chicken skeletal muscles related to their
      histochemical properties.
AB  - 1. Early, M. pubo-ischio-femoralis pars medialis (PIF muscle) and late, M.
      iliotibialis lateralis pars postacetabularis (ITL muscle), maturing muscles were
      studied. These two muscles contained different populations of histochemical fibre
      types. 2. The profile measurements of the muscles showed diphasic allometric
      growth relative to the weights. In the early stage of growth (up to 15 weeks
      after hatching), the muscle length, width and depth all increased, while in the
      later stage (from 15 to 35 weeks) muscle growth resulted mainly from the marked
      increase in the depth and to a lesser degree, from an increase in the width. 3.
      Type I fibres, observed predominantly in PIF muscle matured earlier than the Type
      II fibres of ITL muscle. 4. From these results, the detailed process of skeletal
      muscle growth in the chicken was discussed.

PMID- 8156432
TI  - Measurement of endogenous amino acid losses in poultry.
AB  - 1. Ileal endogenous amino acid losses were determined in broiler chickens and in
      cannulated cross-bred layer strain cockerels using either a nitrogen-free diet,
      regression analysis or a 48 h fast. 2. Endogenous amino acid flows to the ileum
      in fasted cockerels were significantly lower than those obtained both by feeding
      the nitrogen-free diet, and from regression analysis in either broilers or
      cockerels. Regression analysis gave the highest flows. 3. The apparent
      digestibility coefficients of amino acids in a diet containing 200 g/kg crude
      protein were lower in broilers (0.84) than in cockerels (0.88). When corrected,
      by regression analysis, for the contribution of endogenous amino acids, the true
      digestibility coefficients became 0.90 and 0.92 respectively.

PMID- 8156433
TI  - Dietary lysine concentrations from deficient to excessive and the effects on
      broiler chicks.
AB  - 1. An experiment was designed to test the response of broiler chicks (0-21 d) to
      dietary lysine concentration. Concentrations ranged from 9.9 to 14.4 g of lysine
      per kg diet when energy was 13.4 MJ ME/kg. 2. Estimates of the concentration of
      lysine needed for maximum body weights gain, food consumption and gain:food ratio
      were calculated using two statistical methods. An average of these estimates was
      12.0 g lysine/kg diet to 21 d of age. 3. Chicks given 13.9 or 14.4 g lysine/kg
      diet were negatively affected by these concentrations. The decreases in average
      weight gain, food consumption and food efficiency were caused mainly by several
      chicks that developed severe leg problems and were much smaller than their pen
      mates. Chicks with no leg problems gained weight as rapidly as chicks receiving
      optimal amounts of lysine.

PMID- 8156434
TI  - Growth and food intake responses to diets of different protein contents and a
      choice between diets containing two concentrations of protein in broiler and
      layer strains of chicken.
AB  - 1. Food intake, protein intake and body weight gain were measured in male broiler
      and layer strains of chickens offered approximately isocaloric diets containing
      various concentrations of protein from 4 to 9 weeks of age. The carcases were
      analysed for protein, fat and ash. 2. In the first experiment 5 birds of each
      strain were given diets containing either 65, 115, 172, 225 or 280 g protein/kg
      fresh matter. The sixth group was given a choice between 65 and 280 g/kg. There
      was an approximately linear increase in protein deposition with dietary protein
      content up to 280 g/kg with broilers and 225 g/kg with layers. When a choice of
      diets was offered, birds of both strains grew at a rate not significantly
      different from that of birds on the diets with the lowest protein content which
      gave maximal growth given singly, by making an apparently appropriate choice from
      the two diets. 3. In the second experiment broilers were offered a choice of two
      diets in the following combinations: 65 and 115, 65 and 225, 115 and 225, 225 and
      280 and 280, and 320 g/kg protein. They were able to differentiate successfully
      between two diets on the basis of their protein content and, where the two diets
      were on either side of the optimum, to change the proportions selected as they
      grew to match their changing requirement for dietary protein. When given two
      diets, both of which had protein contents lower than the single diets which gave
      maximal growth, birds ate predominantly from that closer to that optimal diet.
      When both diets had a higher protein content than the optimum birds ate mostly
      from that closer to optimum. 4. The results show that growing chickens can match
      their protein intake closely to their requirements when given a pair of diets
      that allows this; if both diets are on the same side of the optimum then the one
      closest to that required is predominantly chosen.

PMID- 8156435
TI  - Effect of a soluble polysaccharide (carboxy methyl cellulose) on the physico
      chemical conditions in the gastrointestinal tract of broilers.
AB  - 1. The effects of an indigestible soluble polysaccharide (carboxy methyl
      cellulose: CMC) on broiler performance (body weight gain, food and water intake)
      and on chyme characteristics (moisture content, viscosity, pH, osmolality and
      retention time) in broilers were studied. 2. In semi-synthetic diets 0, 5.0 and
      10.0 g/kg of cellulose was replaced by CMC on weight basis. These diets were fed
      to male broilers from 3 to 5 weeks of age. 3. When 10.0 g/kg CMC was included in
      the diet, food intake and body weight gain were reduced, compared to the 0, and
      5.0 g/kg CMC diets. Food:gain ratio and water intake were increased at each CMC
      concentration. The significant quadratic response showed an increased response
      per 5.0 g/kg dietary CMC at the higher CMC concentration. 4. The viscosity in the
      supernatant of the chyme was linearly increased in all intestinal segments by
      CMC. A quadratic increase was observed in the crop. In the lower ileum,
      differences between the 5.0 and 10.0 g/kg CMC diets were not significant. 5. CMC
      increased the mean retention time of chromium in the duodenum and in the upper
      jejunum, and reduced the maximal rate of marker excretion. The transit time
      (first appearance of the marker in the excreta), however, was significantly
      reduced at the highest CMC concentration. 6. The osmolality of the intestinal
      fluid decreased less as the chyme moved from the duodenum into the lower ileum,
      with increasing concentrations of CMC. 7. The ileal pH was reduced linearly by
      the CMC content of the diet. 8. Based on a higher moisture content of the chyme
      in the CMC-fed birds, and the higher jejunal and ileal osmolarities in those
      birds, it was concluded that the efficiency of both digestion and absorption was
      reduced by CMC inclusion in broiler diets.

PMID- 8156436
TI  - Effect of a soluble polysaccharide (carboxy methyl cellulose) on the absorption
      of minerals from the gastrointestinal tract of broilers.
AB  - 1. The effect of an indigestible soluble polysaccharide (carboxy methyl
      cellulose: CMC) on the absorption of some macro-elements (sodium, potassium,
      calcium, phosphorus and magnesium) from different segments of the small intestine
      of broilers was determined. 2. In semi-synthetic diets 0, 5.0 and 10 g/kg
      cellulose was replaced by CMC on weight basis. These diets were fed to male
      broilers from 3 to 5 weeks of age. 3. CMC inclusion reduced the rate of mineral
      absorption throughout the small intestine. The effect of CMC on sodium absorption
      was more pronounced than the effects on the absorption of the other minerals. 4.
      The cumulative absorption of all minerals up to the lower jejunum was reduced by
      dietary CMC. This negative effect of CMC on the absorption of minerals was
      alleviated in the lower ileum, except for potassium. 5. The concentrations of
      sodium and magnesium in the chyme supernatant were clearly decreased, while those
      of calcium and phosphorus were increased by dietary CMC inclusion. Taking the
      mineral concentrations in the total chyme into account, the solubilities of
      calcium, phosphorus and magnesium in the ileum were increased by dietary CMC. The
      solubilities of sodium and potassium were not increased. 6. The reduced
      cumulative absorption of minerals from the gastrointestinal tract with increasing
      dietary concentrations of CMC, was probably caused by the higher intraluminal
      viscosities in the small intestine. It is not likely that either the intestinal
      pH, or the time food was retained in successive gastrointestinal segments, will
      have affected mineral absorption negatively in any segment.

PMID- 8156437
TI  - Regulation of plasma oestrogen by dietary fats in the laying hen: relationships
      with egg weight.
AB  - 1. Feeding a diet supplemented with maize oil was found to elevate plasma
      oestradiol concentration in laying hens. 2. In a larger-scale experiment,
      isoenergetic and isonitrogenous diets containing 10, 20, 40 or 60 g/kg
      supplemental maize oil, tallow, coconut oil or fish oil were fed for 5 weeks. 3.
      Egg weights showed very different responses to the different fats. The responses
      could be described by quadratic functions that all gave optimum responses with
      supplemental dietary fat concentrations of about 40 g/kg. Egg weight increased
      the most with maize oil and was decreased with fish oil at the highest inclusion
      rate. 4. Measurements of egg components showed a relatively larger increase in
      albumen weights with maize oil than with other fats. 5. Across treatments, mean
      plasma oestradiol concentrations were very highly correlated (r = 0.96) with the
      changes in egg weights over the experimental period. 6. It is concluded that
      oestrogen is important in controlling egg weight and that the effect of dietary
      fats in influencing egg weight is mediated by an effect of the fats on oestrogen
      metabolism.

PMID- 8156438
TI  - Food allergy in children.

PMID- 8156439
TI  - Vesicular transport of peroxidase in human eosinophilic myelocytes.
AB  - We performed ultrastructural cytochemistry to detect peroxidase in
      developmentally arrested human eosinophilic myelocytes. Human umbilical cord
      blood mononuclear cells were cultured for 21 days in the presence of murine
      derived conditioned media, resulting in the development of eosinophilic
      myelocytes. Unlike normally developing eosinophilic myelocytes, which contain
      peroxidase in synthetic organelles (i.e. cisterns surrounding the nucleus and
      bounded by the rough endoplasmic reticulum and Golgi structures) and in immature
      and mature granules, the developmentally arrested cells showed ultrastructural
      evidence of decreased synthesis and secretory transport of peroxidase. Thus,
      peroxidase was generally absent in the perinuclear and rough endoplasmic
      cisterns, in Golgi structures, in immature granules and in the matrix compartment
      of most mature granules. Rather, biocompartmental specific granules displayed
      empty, peroxidase-negative matrix and central, peroxidase-negative core material.
      Peroxidase was present in perigranular vesicles, some of which were attached to
      granules. Such peroxidase-loaded transport vesicles are similar to those that
      effect piecemeal degranulation of mature human eosinophils cultured in rhIL-5
      containing media [1]. These findings establish vesicle-mediated piecemeal
      degranulation in the secretory repertoire of immature human eosinophils and
      suggest the possibility that eosinophilic myelocytes may participate in vivo in
      important physiological and/or pathological events that require selective
      secretion from the specific granule matrix compartment.

PMID- 8156440
TI  - The pattern of food hypersensitivity in patients with onset after 10 years of
      age.
AB  - One hundred and twelve patients with a history of immediate adverse reaction
      after food ingestion and positive skin test to food are presented with the result
      of food challenge. In all patients the symptoms started after 10 years of age;
      most presented with recurrent short-lasting urticarial rash, often accompanied by
      rhinitis. In the majority of the patients, skin tests were positive to multiple
      food allergens, but 67% of these responded to oral provocation by only one
      allergen. One-third of the patients had a history of allergic symptoms following
      exercise after meals, but in only one-third of these symptoms were reproducible
      in the laboratory. Fruit and vegetables were the main allergens responsible for
      food hypersensitivity. Food allergy can develop after the first 10 years of life.
      Fruit and vegetables are the main cause of food allergy in these patients, while
      milk and egg are the least common. These findings differ from those in early
      childhood where milk and eggs are the main allergens.

PMID- 8156441
TI  - Airborne birch pollen antigens in different particle sizes.
AB  - Two particle samplers for ambient air, situated together: a static size-selective
      bio-aerosol sampler (SSBAS) and a Burkard pollen and spore trap were compared in
      sampling intact birch pollen grains through one flowering period of Betula (a
      total of 44 days). The SSBAS trapped pollen grains three times more efficiently
      than the Burkard trap, but the variations in pollen counts were significantly
      correlated. In contrast, birch pollen antigenic activity and the pollen count in
      the Burkard samples were not closely correlated. The antigenic concentration was
      occasionally high both before and after the pollination period. There was a high
      birch pollen antigenic activity in particle size classes where intact pollen
      grains were absent, even on days when the pollen count was very low.
      Correspondingly, on days with high birch pollen counts in the air, pollen
      antigenic activity was on several occasions low, indicating that pollen grains
      were empty of antigenic material. The small particle size classes are especially
      important to allergic patients because they are able to penetrate immediately
      into the alveoli and provoke asthmatic reactions. Therefore, aerobiological
      information systems based on pollen and spore counts should be supplemented with
      information concerning antigenic activities in the air.

PMID- 8156442
TI  - Sputum eosinophilia after asthmatic responses induced by isocyanates in
      sensitized subjects.
AB  - To assess the nature and the time-course of the cellular component of airway
      inflammation induced by isocyanates, we examined nine subjects with occupational
      asthma induced by toluene- or methylene diphenyl-diisocyanate (TDI, MDI) and four
      control subjects never exposed to isocyanates. Sputum was induced by inhalation
      of ultrasonically nebulized hypertonic saline (3-4% NaCl) before and 8, 24, 48 h
      after inhalation challenge with TDI or MDI. Expectorated samples were incubated
      with dithiothreitol, washed and cytocentrifuged. Differential cell counts were
      obtained on slides stained with May-Grunwald-Giemsa. Metachromatic cells (mast
      cells and basophils) were counted on slides stained with toluidine blue at pH
      0.1. One occupational asthmatic exhibited a dual reaction to TDI, two exhibited a
      single early asthmatic reaction to MDI, six exhibited a late asthmatic reaction
      to TDI (n = 5) or MDI (n = 1), whereas no reactions were observed in control
      subjects after TDI challenge. In sensitized subjects eosinophils increased from a
      median value (interquartile range) of 5 (15)% before challenge to 29 (29)% (P =
      0.014) and to 30 (31)% (P = 0.031) 8 and 24 h after TDI/MDI challenges,
      respectively. Sputum eosinophilia was observed both in early and late reactors
      and declined to near to baseline values 48 hr after challenge. Percentages of
      eosinophils in control subjects did not exceed 7% during the study.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156443
TI  - Hypoallergenic formulae--have they a therapeutic role?

PMID- 8156444
TI  - Safety and efficacy of a 12-week maintenance interval in patients treated with
      Hymenoptera venom immunotherapy.
AB  - It is currently recommended to administer a maintenance dose of 100 micrograms of
      venom at 4-6 week intervals for Hymenoptera venom immunotherapy (VIT). Because
      the optimal duration of therapy is not known, we decided to progressively prolong
      the interval between maintenance injections instead of accepting the risk of
      anaphylactic reactions when VIT is discontinued after a predetermined period. We
      report here on the results of a first phase of this interval extension programme,
      covering the gradual increase of the interval from 1-12 weeks over 19 months in
      178 patients. A 12-week interval maintenance VIT could be achieved in 117/128
      (91%) of yellow jacket venom (YJV) and in 35/50 (70%) of honeybee venom (HBV)
      allergic patients. At the time of the interview these 152 patients had been
      treated with 12-weekly 100 microgram venom injections for an average period of 2
      years without any untoward reaction to VIT. During this period 48 YJV allergy
      sufferers experienced 77 field re-stings without systemic reaction (SR), and 17
      HBV allergic subjects were restung at least 213 times in total, with one patient
      developing a very large local reaction and one a mild systemic reaction. In 26 of
      the 178 patients the interval of 12 weeks was not reached for various reasons,
      with a higher failure rate among the HBV allergic patients. Most Hymenoptera
      venom allergic patients can thus be safely and effectively treated with 12-weekly
      injections of 100 micrograms venom.

PMID- 8156445
TI  - Immunogenicity of a so-called hypoallergenic formula in at-risk babies: two case
      reports.
AB  - The clinical and immunologic findings of two breast-fed babies who experienced
      anaphylaxis after a feeding with a partially whey hydrolysate formula (PWHF) are
      reported. Sensitization to this formula seems to have occurred in the first days
      of life in the Maternity Hospital where the babies were fed the same formula.
      These two case reports suggest that PWHF may be immunogenic in the IgE system.
      This data is in agreement with previous studies which showed intact fragments of
      cow's milk (CM) proteins in PWHF.

PMID- 8156446
TI  - Bronchial provocation with cat allergen: correlation between the individual IgE
      CRIE pattern and the occurrence of a late allergic reaction.
AB  - Twenty-one mild asthmatic patients allergic to cat dander underwent a bronchial
      provocation test (BPT) with a cat extract. An early allergic response (EAR) was
      observed in all 21 patients and a late allergic response (LAR) in 8/21 patients.
      In the EAR, the patients with subsequent LAR had a greater fall in FEV1. Their
      baseline FEV1, and total dose of inhaled allergen were not significantly
      different from patients who did not develop a LAR, but their serum specific IgE
      level was higher. Crossed immunoelectrophoresis (CIE) of the same cat extract
      showed that it contained eight different proteins. An IgE-CRIE was obtained from
      all 21 patients, using radiolabelled anti-IgE and autoradiography. Radiolabelled
      standards allowed a semiquantitative scoring of the radiostaining. The CRIE
      pattern of the eight patients with LAR showed a higher score of radiostaining and
      a greater number of proteins bound to IgE. The two major allergen cat albumin and
      Fel dI bound equally to IgE of patients with and without LAR whereas another
      protein (antigen No. 7) bound to IgE of 100% of patients with LAR but of only 38%
      of patients without LAR. These data suggest that the pattern of the IgE response
      to specific proteins of a cat extract may be related to the occurrence of LAR
      after BPT with this allergen.

PMID- 8156447
TI  - A three-year double-blind placebo-controlled study with specific oral
      immunotherapy to Dermatophagoides: evidence of safety and efficacy in paediatric
      patients.
AB  - Very few double-blind trials of oral immunotherapy have been reported. The
      majority of these have been performed with pollen extracts and the results have
      often been equivocal. The major weaknesses of these studies have been the short
      periods of the trials, the low doses of allergen employed and inadequate
      evaluation of efficacy. The present study has involved a placebo-controlled
      double-blind trial of oral immunotherapy for three years with Dermatophagoides
      pteronyssinus at relatively high doses in 18 paediatric patients. Throughout the
      trial clinical parameters (symptom and medication scores) and immunological
      parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess
      the safety and efficacy of the treatment. The treatment was well tolerated by all
      patients and no side-effects were experienced. Clinical improvement was evident
      after the second year of therapy and this was confirmed by a significant
      reduction in conjunctival reactivity assessed by a specific conjunctival
      provocation test. In addition, there were significant changes in the
      immunological parameters with a reduction in specific IgE and increased levels of
      IgG4 and IgG1, results in keeping with previous studies of oral and subcutaneous
      immunotherapy. Although the results do not provide an explanation of the basis of
      successful oral immunotherapy, they clearly demonstrate the efficacy and safety
      of the treatment and suggest that it may be a useful and more acceptable
      alternative for patients than the traditional subcutaneous immunotherapy.

PMID- 8156448
TI  - Attenuation of allergic airway inflammation in IL-4 deficient mice.
AB  - To investigate the role of IL-4 in vivo in allergic asthma, we developed a murine
      model of allergen-induced airway inflammation. Repeated daily exposures of
      actively immunized C57BL/6 mice to aerosolized ovalbumin (OVA) induced a
      peribronchial inflammation and an increase in eosinophils and lymphocytes in
      bronchoalveolar-lavage (BAL) fluid. In IL-4 deficient (IL4-/-) mice, treated in
      the same way, there were substantially fewer eosinophils in BAL and much less
      peribronchial inflammation compared with wild type mice. In this model, mast cell
      deficient (W/Wv) mice developed a similar degree of BAL eosinophilia and
      peribronchial inflammation as wild type mice, demonstrating that the mast cell is
      not required for the induction of chronic airway inflammation. In contrast, BAL
      eosinophilia and airway inflammation were absent in OVA-treated MHC ClassII
      deficient (B6.Aa-/-) mice which lack mature CD4+ T lymphocytes. In conclusion,
      these results indicate that IL-4 is a central mediator of allergic airway
      inflammation, regulating antigen-induced eosinophil recruitment into the airways
      by a T cell dependent mechanism.

PMID- 8156449
TI  - The anti-inflammatory effects of cetirizine.

PMID- 8156450
TI  - AIDS and dentistry.

PMID- 8156451
TI  - Latex allergy and spina bifida.

PMID- 8156452
TI  - Maggots in the news.

PMID- 8156453
TI  - The practice of dentistry in the drought areas of the west. 1935.

PMID- 8156454
TI  - Re-engineering the dental practice.
AB  - Although this is the last in our three-part series on re-engineering, it's
      unlikely to be the last word you'll hear on the subject. The organizations that
      experience continued success as we approach the next millennium will be those
      that can adapt to the ever fluid economy by making core--not cosmetic--changes.
      And it is the concept and implementation of re-engineering that will provide the
      model for doing just that.

PMID- 8156455
TI  - A new era of dentistry: patient education and case acceptance.

PMID- 8156456
TI  - Infection control considerations when designing and equipping a dental office.

PMID- 8156457
TI  - Informed consent--the process.

PMID- 8156458
TI  - Would you recognize fraud in your practice?

PMID- 8156459
TI  - The effects of spiramycin and/or scaling on advanced periodontitis in humans.
AB  - It has long been questioned whether antibiotics, used as a supplement to
      traditional therapy, provide any lasting benefit in the treatment of chronic
      periodontitis. This study was designed to evaluate Spiramycin as an adjunct to
      scaling and root planing in the treatment of advanced chronic periodontitis. In
      total, 193 patients with advanced periodontitis were recruited in seven centres
      using selection criteria previously described. After undergoing thorough scaling
      and root planing, all patients randomly received either Spiramycin, 1,500,000
      international units, twice per day (IU, bid) for 14 days (96 patients), or a
      visually-identical placebo capsule (97 patients). The clinical parameters
      measured were plaque index, crevicular fluid level, probing depths, bleeding on
      probing and attachment level changes. Data was recorded at baseline, two-, eight
      , 12- and 24-weeks visits. A total of 189 patients completed the study (96
      placebo, 93 Spiramycin). Statistically significant differences in probing depth,
      favoring Spiramycin, were seen at two weeks (p < 0.0125), eight weeks (p <
      0.0020), 12 weeks (p < 0.0032) and 24 weeks (p < 0.0075). Spiramycin also
      produced a significant improvement in attachment level at 12 weeks (p < 0.0146).
      All other clinical parameters showed no difference between drug and placebo. This
      study shows that Spiramycin, as an adjunct to thorough scaling and root planing,
      provides a statistically significant improvement in probing depths for up to 24
      weeks when compared with scaling and root planing alone. Both longer studies and
      microbiologic evaluations are necessary to determine whether a more lasting
      benefit is possible.

PMID- 8156460
TI  - Tobacco counselling among Alberta dentists.
AB  - Evidence suggests that dentists, with their existing commitment to prevention and
      their opportunity for regular interaction with patients, have the potential to
      significantly decrease tobacco-related morbidity and mortality. In 1992, dentists
      belonging to the Alberta Dental Association were surveyed to determine their
      attitudes, behavior and perceived obstacles to tobacco counselling. The 755
      respondents represent 55 per cent of the province's practising dentists. Their
      attitudes toward involvement in tobacco counselling varied. Over 90 per cent
      agreed that dentists should show leadership and set a good example. However, only
      60-70 per cent indicated that they should try to convince or actively help
      patients quit, and 25 per cent indicated that intervention was not appropriate.
      Little difference was found in the preferred counselling approach, with most
      dentists limiting their counselling efforts to discussing the hazards of smoking
      and benefits of quitting. Very few provided patients with specific strategies to
      change their smoking behavior. Perceived obstacles to tobacco counselling
      included a lack of coordination and exchange of information between dentistry and
      cessation services, pessimism about the patients' ability to change their tobacco
      habit, the need for further training, and the fact that counselling was not a
      high priority. This survey suggests that dentists could expand their role as
      tobacco counsellors. Professional associations and educational institutions have
      the potential to greatly assist the dental community in this regard, and
      attention should be given to the development and dissemination of informational
      campaigns and educational workshops.

PMID- 8156461
TI  - [Lasers in dentistry and in oral and maxillofacial surgery].
AB  - During the last few years, lasers have begun to appear in dentistry. There are,
      however, different types of lasers and different therapeutic indications in
      almost every field of dentistry. This is a review of the current literature on
      the applications of lasers in oral and maxillofacial surgery.

PMID- 8156462
TI  - Criteria for the accreditation of noninvasive vascular laboratories.

PMID- 8156463
TI  - 1. Carotid surgery: a historic perspective.
AB  - The development of the appropriate role for surgery on the carotid artery has
      mirrored many other advances in the field of health care. The acceptance of this
      intervention has differed amongst specialties, and only recently has undeniable
      evidence of its efficacy been presented. The invention of carotid angiography
      established a direct link between plaque at the carotid bifurcation and stroke.
      The operations steadily gained popularity from 1971, when 17,000 procedures were
      performed, until the mid-1980s, when over 100,000 procedures were performed in
      North America. The North American Symptomatic Carotid Endarterectomy Trial was
      initiated to test the question of whether adding carotid endarterectomy to
      maximum medical therapy reduces the risk of stroke in patients with focal
      temporary neurologic deficits. Canadian vascular surgeons embraced this study
      with enthusiasm and contributed to the successful completion of the first part of
      the trial. The role for surgery in those patients who fit into the study
      categories is clear, but a need for surgical judgement exists for other groups of
      patients and must remain a pivotal tool for directing surgical intervention.

PMID- 8156464
TI  - 3. Surgical management of internal carotid artery stenosis: preventing
      complications.
AB  - Although the North American Symptomatic Carotid Endarterectomy Trial and the
      European Collaborative Trial demonstrated the efficacy of carotid surgery for the
      prevention of stroke in patients with symptomatic high grade stenosis, it is
      important to remember that within the surgical arms of these studies the
      perioperative stroke rate was 5.5% and 7.5% respectively. Few studies have
      addressed the factors responsible for perioperative stroke. In a recent report
      from our institution, 66 of 3062 carotid endarterectomies were complicated by
      perioperative stroke. Of these, 65% were due to a failure in surgical technique.
      The mechanisms of failure included ischemia during carotid clamping (10),
      postoperative thrombosis and embolism (25) and other factors (8). Strokes not
      related to technical failures were due to reperfusion injuries and intracranial
      hemorrhage (12) and other events in the postoperative period (30 days). Specific
      problems and possible solutions are discussed. Further improvements in the
      technique of carotid endarterectomy may lead to lower complication rates and a
      wider acceptance of surgery for the prevention of stroke.

PMID- 8156465
TI  - 4. Current status of operative treatment for asymptomatic carotid stenosis.
AB  - OBJECTIVE: To determine the natural history of asymptomatic carotid stenosis and
      the effect of prophylactic carotid surgery on neurologic morbidity and mortality.
      DESIGN: A prospective, randomized, cooperative study, with a mean follow-up of
      47.9 months. SETTING: Ten Veterans Administration hospitals across the United
      States. PATIENTS: The study comprised 436 patients who were divided into two
      groups: group 1, patients with symptomatic unilateral carotid disease, who were
      treated with carotid endarterectomy, and had contralateral asymptomatic stenosis;
      group 2, patients with significant asymptomatic carotid disease. Carotid stenosis
      was confirmed by arteriography, which demonstrated at least 50% stenosis,
      measured by comparing the least transverse diameter of the stenosis on lateral
      arteriography. INTERVENTIONS: Ocular plethysmography, duplex scanning and
      arteriography; carotid endarterectomy and acetylsalicylic acid or acetylsalicylic
      acid alone. RESULTS: The 436 patients were randomized between nonoperative
      (medical) (233) and operative (surgical) (211 procedures on 203 patients) groups.
      In the surgical group, the 30-day mortality was 1.9% and the permanent neurologic
      morbidity was 2.4%, for a combined stroke and death rate of 4.3%. The incidence
      of neurologic events was 8% in the surgical group compared with 20.6% in the
      medical group, for an absolute reduction in risk of 12.6% (p < 0.001).
      CONCLUSION: Carotid endarterectomy, combined with optional medical management,
      can reduce the incidence of ipsilateral neurologic events in high-risk men with
      arteriographically confirmed asymptomatic carotid stenosis.

PMID- 8156467
TI  - Necrotic stenosis of the right colon secondary to acute pancreatitis.
AB  - The authors report the case of a 52-year-old man who had stenosis and necrosis of
      the right colon secondary to acute pancreatitis. The right colon is a very
      uncommon location for this complication. The site of the stenosis was documented
      by contrast enema examination and computed tomography. Although conservative
      management is usually advocated for the initial management of this complication,
      laparotomy was necessary when the patient's condition failed to improve with
      conservative therapy. Colonic necrosis was found at laparotomy, and a partial
      colectomy was carried out, followed later by ileocolic reanastomosis. The authors
      emphasize the diagnostic and treatment options for this entity.

PMID- 8156466
TI  - Heterotopic ossification after primary cemented and noncemented total hip
      arthroplasty in patients with osteoarthritis and rheumatoid arthritis.
AB  - OBJECTIVE: To compare the frequency and severity of heterotopic ossification (HO)
      in patients with osteoarthritis or rheumatoid arthritis who undergo cemented or
      noncemented total hip arthroplasty. DESIGN: A prospective case study. SETTING: A
      university referral centre. PATIENTS: One hundred and sixty one patients
      underwent 184 total hip arthroplasties. The 184 hips were categorized as follows:
      cemented total hip arthroplasty--60 osteoarthritis hips, 26 hips affected by
      rheumatoid arthritis; noncemented total hip arthroplasty--67 osteoarthritic hips,
      31 hips affected by rheumatoid arthritis. INTERVENTIONS: Total hip arthroplasty.
      A standard approach was used to implant either a cemented or noncemented
      prosthesis. Radiographs were obtained of each hip preoperatively, immediately
      postoperatively and 6 weeks, 3 months, 6 months and 1 year postoperatively. MAIN
      OUTCOME MEASURES: Radiographs were graded in blind fashion for HO, according to
      the criteria of Brooker. Modified Harris hip scores were calculated at 1 and 2
      years postoperatively. RESULTS: HO (incidence of Brooker grades 2, 3 and 4) was
      greater after cemented (22%) than noncemented (9%) total hip arthroplasty in
      osteoarthritic hips (p < 0.05), but there was no significant difference between
      the two types of prosthesis in hips affected by rheumatoid arthritis. When both
      types of prosthesis were considered together there was no significant difference
      in the incidence of HO between osteoarthritic hips (15%) and hips affected by
      rheumatoid arthritis (12%). With respect to Harris hip score, the presence of
      grade 4 HO was associated with a significantly (p < 0.05) lower score (50.6) than
      grade 3 (89.4) and grade 2 (91) HO. CONCLUSIONS: Cemented total hip arthroplasty
      increases the frequency of HO only in osteoarthritic hips. Compared with
      Brooker's grades 2 and 3 HO, grade 4 HO significantly lowers the Harris hip score
      after total hip arthroplasty.

PMID- 8156468
TI  - Synergistic effects of tumour necrosis factor and morphine on gut barrier
      function.
AB  - OBJECTIVE: To study the effects of tumour necrosis factor (TNF) and morphine on
      intestinal permeability, intestinal transit and bacterial translocation in the
      rat. DESIGN: A randomized interventional controlled experiment. SETTING:
      University surgery and microbiology research laboratory. PARTICIPANTS: Forty-four
      rats in five groups as follows: control (n = 9); treated with morphine every 2
      hours for 8 hours (n = 9); treated with TNF for 5 minutes (n = 10); treated with
      TNF plus morphine every 2 hours for 8 hours (n = 6); and treated with TNF plus
      morphine every 3 hours for 24 hours (n = 10). MAIN OUTCOME MEASURES: Intestinal
      permeability as measured by the uptake of chromium-51 ethylenediaminetetraacetate
      (51Cr-EDTA) over 8 hours, intestinal transit as measured by the amount of 51Cr
      EDTA remaining in the gastrointestinal tract at the time of animal sacrifice,
      intestinal bacteria counts and translocation of bacteria as measured from
      bacterial counts of mesenteric lymph nodes, spleen and liver at the time of
      sacrifice. RESULTS: Morphine increased intestinal transit time and ileal bacteria
      counts (p < 0.05). TNF alone did not increase intestinal permeability or
      bacterial translocation. TNF plus morphine increased intestinal transit time,
      intestinal permeability, bacterial counts and bacterial translocation (p < 0.05).
      CONCLUSIONS: Morphine or increased intestinal transit time, or both, increases
      the concentration of intestinal bacteria. Morphine plus TNF increases intestinal
      bacteria counts, intestinal permeability and bacterial translocation. Morphine
      alone does not increase intestinal permeability or bacterial translocation.

PMID- 8156469
TI  - Photodynamic therapy for atherosclerotic stenoses in Yucatan miniswine.
AB  - OBJECTIVE: To determine the feasibility of treating atherosclerotic stenoses with
      photodynamic therapy (PDT). DESIGN: A prospective study with a 4-week follow-up.
      SUBJECTS: Twelve Yucatan miniswine, weighing between 25 and 35 kg. INTERVENTIONS:
      Aortoiliac atherosclerosis was created by a combination of balloon endothelial
      injury and dietary supplementation with 2% cholesterol and 15% lard for 7 weeks.
      Then the miniswine were given a porphyrin-type photosensitizer (Photofrin), 2.5
      mg/kg intravenously, and treated with 630 nm light through an intravascular,
      cylindrical, diffusing fibreoptic probe, which was coupled to an argon-pumped dye
      laser to supply 120 J of laser energy. MAIN OUTCOME MEASURES: Differences in
      luminal narrowing before and after PDT. RESULTS: Seven miniswine had an increase
      in luminal diameter, but five had no increase. Microscopy demonstrated a broad
      range of features in treated vessels, including areas with re-endothelialization
      and regions of platelet and blood cell adherence with absent or abnormal
      endothelium. CONCLUSION: Although this study demonstrated resolution in stenoses
      for some miniswine, questions concerning light dosimetry, mechanism of action and
      long-term effects remain to be determined.

PMID- 8156470
TI  - Laparoscopic nephrectomy: the learning-curve experience.
AB  - OBJECTIVE: To report the learning-curve experience with laparoscopic nephrectomy.
      DESIGN: Case series. SETTING: A tertiary-care referral centre serving southern
      Saskatchewan. PATIENTS: Sixteen patients (7 men, 9 women), selected to undergo
      laparoscopic nephrectomy. They ranged in age from 19 to 83 years. Indications for
      surgery were: recurrent atrophic pyelonephritis with pain (three patients),
      obstruction at the ureteropelvic junction with pain (three), small ectopic kidney
      with pain (one), renovascular hypertension (two), a solid renal mass confirmed by
      computed tomography (four), Staghorn calculus (one), transitional cell tumour of
      upper ureter (one) and pyonephrosis with a nonfunctioning kidney (one).
      INTERVENTIONS: Laparoscopic nephrectomy. MAIN OUTCOME MEASURES: Postoperative
      morbidity, complications of the procedure and duration of postoperative
      hospitalization. RESULTS: Kidneys were removed laparoscopically in 13 patients.
      Open nephrectomy was necessary in three patients, owing to a lack of experience
      in patient selection in two cases and to intraoperative hemorrhage in the third.
      All patients resumed oral intake on the 1st postoperative day, and most did not
      require analgesics for relief of pain beyond 36 hours postoperatively.
      Complications of laparoscopic nephrectomy included pneumonia (one patient), low
      grade fever (two patients), need for blood transfusion (three patients) and
      transient ischemic attack (one patient). The mean postoperative hospital stay was
      4.3 days. CONCLUSIONS: When patients are properly selected, laparoscopic
      nephrectomy provides decreased postoperative morbidity, a shorter convalescence,
      and thus cost savings, compared with open nephrectomy.

PMID- 8156471
TI  - Successful management of postoperative chylothorax with fibrin glue in a
      premature neonate.
AB  - Chylothorax is a potentially serious condition that may complicate a variety of
      thoracic operations, particularly cardiothoracic procedures for congenital heart
      disease. Conservative therapy with chest tube drainage of the chyle fluid and
      dietary manipulations is frequently effective. When conservative treatment fails,
      surgery may be necessary. In this report, the authors discuss their recent
      experience with fibrin glue in the management of a 600-g premature neonate who
      had a postoperative chylothorax. Recent trends in the management of this
      difficult problem are also discussed.

PMID- 8156472
TI  - Heparin-induced thrombosis treated with ancrod.
AB  - Heparin used in the treatment of thromboembolic disease may produce an immune
      response in the patient, leading to thrombocytopenia and even thrombosis. These
      complications may arise at any time after the institution of heparin therapy. The
      authors report a case of heparin-induced thrombocytopenia with thrombosis in a 70
      year-old woman. The complication was treated successfully with thrombectomy and
      the administration of warfarin and ancrod, which is a natural fibrinolytic agent.
      The nature of heparin-induced thrombosis and the mechanism of action of ancrod
      are discussed. The authors emphasize that all patients receiving heparin therapy
      should be closely monitored to detect hematologic disorders and to prevent their
      sequelae. Ancrod provides a reasonable therapeutic option if thrombosis does
      occur.

PMID- 8156473
TI  - Late recurrence of testicular cancer.
AB  - Late recurrence of nonseminomatous germ cell tumours of the testis is rare. The
      authors report on a 35-year-old man treated initially for embryonal cell
      carcinoma of the testis with metastases, who presented 12 years later with an
      increasing serum alpha-fetoprotein level and a biopsy-proven embryonal cell
      cancer in the hilus of the left lung. Because the tumour was highly resistant to
      two separate courses of cis-platinum-based chemotherapy and one course of
      radiotherapy, surgical resection for salvage was carried out. The patient was
      free of disease 3.5 years after the second operation. The possible reasons for
      the occurrence of this highly resistant metastatic testicular cancer are
      discussed. They include a second primary tumour and malignant degeneration of the
      original tumour. In this patient the latter cause was the most plausible.

PMID- 8156474
TI  - Guidelines for the vascular laboratory.

PMID- 8156475
TI  - Toward universal prophylaxis of heterotopic ossification after total hip
      arthroplasty.

PMID- 8156476
TI  - Heterotopic ossification after total hip arthroplasty.

PMID- 8156477
TI  - Carotid endarterectomy.

PMID- 8156478
TI  - Carotid endarterectomy.

PMID- 8156479
TI  - Preoperative cardiac evaluation of the patient with vascular disease.
AB  - OBJECTIVE: To review the literature and evaluate the investigation of cardiac
      risk factors, by tests and intraoperative predictors, that will identify patients
      at high risk for vascular surgery. DATA SOURCES: An English-language literature
      review of Index Medicus articles from 1961 to 1992. STUDY SELECTION: Published
      articles that addressed preoperative risk factors, diagnostic tests and
      intraoperative predictors were selected by multiauthor consensus. DATA
      EXTRACTION: Independent extraction by multiple authors was utilized to abstract
      and assess the quality of data from selected references, with consensus
      determining inclusion or exclusion. DATA SYNTHESIS: From evaluation of published
      data, a number of factors were considered to put a patient scheduled to undergo
      vascular surgery at higher risk: symptomatic coronary artery disease; clinical
      evidence of coronary artery disease, congestive heart failure, aortic stenosis
      and recent myocardial infarction; laboratory findings of significant disease with
      cardiomegaly or significant dysrhythmias; and no symptoms but two or more risk
      factors. CONCLUSIONS: The authors propose an algorithm for the investigation of
      patients and stratification of risk to be considered in weighing the dangers
      versus the benefits of vascular surgery.

PMID- 8156480
TI  - Radiotherapy-induced lung cancer among women who smoke.

PMID- 8156481
TI  - Factors influencing noncompliance and contamination in a randomized trial of
      "Western" (r1) versus "Japanese" (r2) type surgery in gastric cancer.
AB  - BACKGROUND: A randomized trial was undertaken comparing the Western R1 resection
      with limited N1-level lymphadenectomy and the Japanese R2 resection with extended
      lymphadenectomy, including the N2-level for curative resection of gastric cancer
      patients. After 389 patients were entered in the trial, protocol deviations were
      observed that reduced the intended distinction between the two types of
      lymphadenectomy: noncompliance, i.e., no substantiation of lymphadenectomy by
      nodal yields of indicated stations, and contamination, i.e., extension of
      lymphadenectomy outside the allocated level of nodal clearance. METHODS: To
      identify factors underlying these protocol deviations, the authors analyzed the
      influence of six patient-, tumor, and treatment-related characteristics on the
      magnitude of deviations per patient, and on the incidence of deviations per lymph
      node station. RESULTS: Protocol deviations were influenced by the following
      station-specific factors: (1) the number of nodes per station; (2) the clarity of
      anatomical station definition; (3) the location of stations; (4) local
      conventions on the type of gastrectomy; and (5) technical features to allow
      complete en bloc dissection. Furthermore, nonspecific factors such as inadequate
      retrieval of nodes, incomplete dissection, and careful selection of clinically
      overt metastases outside the allocated level of nodal clearance were randomly
      distributed over stations, and they, too, contributed to the deviations.
      CONCLUSIONS: Based on the findings, the authors took additional steps to preserve
      the distinction between limited and extended lymphadenectomy and to improve the
      accuracy of nodal staging. These factors should be considered when
      standardization of both surgicopathologic trials and clinical protocols for the
      treatment of gastric cancer is pursued.

PMID- 8156482
TI  - Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil,
      leucovorin, and cisplatin therapy in patients with advanced colorectal cancer.
AB  - BACKGROUND: Because of experimental and preliminary clinical evidence that
      additional modulation of the biochemical pharmacology and cytotoxicity of 5
      fluorouracil (5-FU) and leucovorin (LV) may be possible by combination of these
      agents with cisplatin (CDDP), the authors undertook a prospective randomized
      trial in patients with colorectal cancer. METHODS: Between 1989 and 1992, 138
      patients with advanced measurable colorectal cancer previously unexposed to
      chemotherapy were randomly assigned to treatment with either 5-FU (425 mg/m2) and
      LV (20 mg/m2) for 5 days, or the combination of 5-FU and LV in the same daily
      dose plus cisplatin (20 mg/m2), each drug given for 4 consecutive days. In both
      treatment arms, courses were administered every 28 days, if toxicity allowed, for
      a total of 6 months or until evidence of tumor progression. RESULTS: The overall
      responses (complete and partial response) were 19% and 28% for the 5-FU/LV and
      the 5-FU/LV/CDDP treatment arms, respectively. Although the three-drug
      combination appeared superior to 5-FU/LV for time to progression or death (8.5
      versus 5.2 months; P = 0.042), there was no evidence that the adoption of
      cisplatin will translate into a definite survival advantage. A comparative
      analysis of the toxicities experienced by the patients in the two treatment
      groups showed a comparable rate, although severe side effects (P < 0.05),
      specifically stomatitis (P = 0.013), were noticed more frequently in patients
      treated with 5-FU/LV for 5 days. CONCLUSIONS: These results suggest that the
      therapeutic index of 5-FU/LV in metastatic colorectal cancer may be improved with
      the addition of cisplatin. However, the somewhat better therapeutic activity and
      lower incidence of severe gastrointestinal side effects have to be weighed
      against additional pharmaceutical charges and the need for a more intense
      antiemetic regimen.

PMID- 8156483
TI  - Epidermoid carcinoma of the anal canal. Results of curative-intent radiation
      therapy in a series of 270 patients.
AB  - BACKGROUND: Epidermoid carcinoma of the anal canal is an uncommon disease, and
      most institutions have only a small series of patients. The current study of a
      large series of patients treated with radiation therapy in a single institution
      evaluates the outcome, prognostic factors, and the late complications for these
      patients. METHODS: From 1972 to 1991, 270 patients with anal canal epidermoid
      carcinoma without evident distant metastasis were irradiated with curative intent
      in the Radiotherapy Department of Tenon Hospital. The sex ratio was 1 man/5.7
      women, with a mean age of 67.5 years. The histology included 59.6% well
      differentiated epidermoid carcinoma, 32.2% moderately or poorly differentiated
      epidermoid carcinoma, and 8.2% cloacogenic. The T-classification was: T1: 8.5%;
      T2: 51.1%; T3: 30.4%; T4: 10%. Abnormal inguinal lymph nodes were present in
      12.5% of the patients. Patients were irradiated by external beam. They received a
      first course of photon irradiation consisting of (mostly 18 mV or 25 mVl; some
      Co60 or 6 mV) 40-45 Gy (box technique) in the pelvis for 4-5 weeks. After a rest
      of 4-6 weeks, a second course of 15-20 gy in 2 weeks was given through a perineal
      field by an electron beam of suitable energy. When rectal involvement was
      important, a four-field, small box technique was used. Fourteen patients were
      given a booster irradiation of 30 Gy by interstitial brachytherapy (Iridium 192
      sources), and four patients were treated with interstitial brachytherapy alone,
      to a mean dose of 62.5 Gy. RESULTS: At 5 and 10 years, determinate survival rates
      were: T1: 86% and 86%; T2: 86.2% and 82.5%; T3: 60.1% and 56.8%; T4: 45% and 45%,
      respectively. The overall local control rate was 80%. The overall anal
      conservation rate was 67%. In 154 patients (57%), the anus had maintained its
      normal function. At 5 and 10 years, determinate survival was 76% and 73.7%,
      respectively, for N0 and 53.5 and 53.5% for clinically involved inguinal lymph
      nodes. According to the log-rank test, survival comparisons between T2 and T3
      classifications and of tumor sizes less than or equal to 4 cm in length and
      greater than or equal to 5 cm in length were significant (P = 0.0001 and P <
      0.0001, respectively). The presence of clinical abnormal inguinal lymph nodes had
      a significant negative influence on survival rates (P = 0.047). Multivariate
      analysis indicated that T-classification and tumor size in centimeters were the
      only predictive variables. Nonpredictive variables included nodal status,
      histology, age, total dose, overall treatment time, and irradiation technique.
      The grade 3 complication rate requiring surgical treatment was 27/270 (10%),
      considering all patients (27/190 represents a 14% rate for patients who had local
      tumor control after radiation therapy alone without secondary salvage
      amputation). There was no significant relationship between complication rate and
      the aforementioned variables. Because of the homogeneity of the irradiation
      doses, no significant relationship was found between dose, local control rate, or
      complication rate. CONCLUSIONS: After radiation therapy, recognizing the
      distinction between tumor sizes of less than or equal to 4 cm in length and more
      than 4 cm in length (which is not considered in TNM Classification criteria
      [International Union Against Cancer, 1987]) could help to improve treatment
      strategies. For tumors more than 4 cm in length and/or with clinically involved
      lymph nodes, the treatment should be more extensive with combined chemotherapy
      and radiation therapy, but the increased local control with the addition of
      cytotoxic chemotherapy to irradiation has not been proven.

PMID- 8156484
TI  - Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic
      features.
AB  - BACKGROUND: Carcinoid tumors of the gastrointestinal tract are most common
      localized in the appendix, followed by the small intestine, the rectum, and the
      stomach. The localization of these tumors at the ampulla of Vater is extremely
      seldom. METHODS: In the present study the authors describe two patients with
      carcinoid tumors of the ampulla Vater and review 71 previously published cases.
      RESULTS: Most patients presented with jaundice, but without carcinoid syndrome.
      Because the tumor grows submucosally, preoperative diagnosis was correct only in
      15%. Most tumors were around 2 cm in size. Metastasis to lymph nodes and/or liver
      was present in 45%. Standard treatment is Whipple resection or local excision in
      small tumors. CONCLUSIONS: Carcinoid tumors of the ampulla of Vater are an
      extremely rare clinical entity. Generally, the prognosis is good with a 5-year
      survival period of 90%.

PMID- 8156485
TI  - Detection of point mutations in the K-ras oncogene at codon 12 in pure pancreatic
      juice for diagnosis of pancreatic carcinoma.
AB  - BACKGROUND: Mutations in the K-ras oncogene at codon 12 are detected at a
      remarkably high frequency in pancreatic carcinomas and are believed to be a
      critical event in oncogenesis. The authors attempted to detect K-ras mutations in
      DNA obtained from pure pancreatic juice collected endoscopically, as a novel
      diagnostic approach to pancreatic carcinoma. METHODS: K-ras mutations were
      examined using the two-step polymerase chain reaction (PCR) combined with
      restriction enzyme digestion, followed by nonradioisotopic single-strand
      conformation polymorphism (SSCP) analysis. RESULTS: Specific mutations of the K
      ras gene at codon 12 were found in six of nine (67%) duct cell carcinomas, all of
      which were negative by cytodiagnosis of the same pure pancreatic juice. K-ras
      mutations were not detected in the pancreatic juice from 14 healthy control
      subjects, 10 patients with chronic pancreatitis, or 3 patients with islet cell
      tumors. CONCLUSIONS: Detection of K-ras mutation at codon 12 in pancreatic juice
      is highly specific for diagnosing pancreatic duct cell carcinoma and may be a
      valuable diagnostic modality for pancreatic carcinoma and for differentiating
      chronic pancreatitis from carcinoma.

PMID- 8156486
TI  - DNA or cell kinetics flow cytometry analysis of 33 small gastrointestinal cancers
      treated by photodynamic therapy.
AB  - BACKGROUND: Photodynamic therapy (PDT) mediated by hematoporphyrin derivative
      (HPD) is a new treatment for cancers of small volume undergoing Phase II or III
      clinical trials in various medical fields. However, there is a lack of prognostic
      criteria of efficacy as in other cancer treatment. METHODS: Cell DNA content or
      cell kinetics throughout the cell cycle were analyzed by flow cytometry and
      propidium iodide staining before and after HPD-PDT in 33 patients with Tis or T1
      cancers of the gastrointestinal tract. The authors compared results in near
      diploid cancers with those obtained in normal corresponding tissue. RESULTS:
      Complete local tumor destruction and negative histologic findings (complete
      response [CR]) were observed in 17 of 33 patients during a period averaging 15.7
      months. Flow cytometry DNA analysis was feasible in 32 patients. Aneuploidy,
      found in 15 of the 32 indicated a poor prognosis because 5 of 15 patients with
      aneuploid tumors were classified as having CR, compared with 12 of 17 patients
      with near-diploid tumors (P < 0.05). Changes in ploidy after PDT in 11 patients
      consisted of a reduction in the number of aneuploid peaks in 8 patients and the
      appearance of one aneuploid peak in 3 patients. Percentages of cells in SG2M
      phase in near-diploid tumors differed from those observed in control subjects for
      adenocarcinomas, and there was no significant decrease after HPD-PDT. There was
      no correlation between the decrease of SG2M cells and the response to HPD-PDT.
      CONCLUSION: Results obtained with PDT in this series of patients confirm
      previously published findings. Changes occurring in the ploidy of PDT-treated
      patients demonstrate that PDT acts directly on cancer cells in humans and not
      only on tumor vasculature. However, response to PDT varies from one cell
      population to another. The appearance of aneuploid populations after PDT suggests
      that destruction of sensitive cell populations allows the growth of aneuploid
      clones that initially are not detectable by flow cytometry.

PMID- 8156487
TI  - Photodynamic therapy and/or external beam radiation therapy for
      roentgenologically occult lung cancer.
AB  - BACKGROUND AND METHODS: Thirty-nine roentgenologically occult lung cancers in 29
      patients were treated using photodynamic therapy (PDT) and/or thoracic
      radiotherapy (TRT) from January 1986 to March 1992. With the exception of one
      mixed-tumor case, all were squamous cell carcinomas. RESULTS: Initial PDT
      achieved complete responses in 25 of 39 (64%) of the cancers. Of the remaining 14
      cancers that showed less than complete response (CR), 10 of the 14 (71.4%) showed
      a CR when subsequently treated with TRT, yielding an overall CR rate of 89.7% for
      cancers treated. Although nine patients experienced recurrences, six of these had
      CR when treated with PDT and/or TRT. To date, 22 patients are alive. Causes of
      death in the patients enrolled in this study are as follows: pyothorax (2); heart
      failure due to pulmonary hypertension (1); chronic respiratory insufficiency (1);
      subsequent primary brain cancer (1); and subsequent primary lung cancer (1). Only
      one died of primary lung cancer. CONCLUSIONS: These findings suggest that PDT
      and/or TRT may be used as an alternative to surgery in the treatment of selected
      patients with roentgenologically occult lung cancer.

PMID- 8156488
TI  - Increased risk of lung cancer after breast cancer radiation therapy in cigarette
      smokers.
AB  - BACKGROUND: Ionizing radiation is a lung carcinogen in a variety of settings,
      including after breast cancer radiation therapy. The authors explored whether
      cigarette smoking and breast cancer radiation therapy have a multiplicative
      effect on the risk of subsequent lung cancer. METHODS: This case-control study
      investigated women registered with primary breast cancer in the Connecticut Tumor
      Registry who developed a second malignancy between 1986 and 1989. Those diagnosed
      with a subsequent primary lung cancer were compared with those diagnosed with a
      subsequent nonsmoking, nonradiation-related second malignancy, and age-adjusted
      odds ratios were calculated with logistic regression. RESULTS: No radiation
      effects were observed within 10 years of initial primary breast cancer. Among
      both smokers and nonsmokers diagnosed with second primary cancers more than 10
      years after an initial primary breast cancer, radiation therapy was associated
      with a 3-fold increased risk of lung cancer. A multiplicative effect was
      observed, with women exposed to both cigarette smoking and breast cancer
      radiation therapy having a relative risk of 32.7 (95% confidence interval [CI],
      6.9-154). The radiation carcinogenic effect was observed only for the ipsilateral
      lung and not for the contralateral lung both in smokers and nonsmokers.
      CONCLUSIONS: Breast cancer radiation therapy, as delivered before 1980, increased
      the risk of lung cancer after ten years in nonsmokers, and a multiplicative
      effect was observed in smokers. For both smokers and nonsmokers, this effect was
      observed only for the ipsilateral lung and not the contralateral lung. Modern
      techniques, however, significantly decrease the radiation dose to the lungs,
      which may decrease the risk of lung cancer. Nonetheless, due to the available
      choices in early-stage breast cancer treatment, current practices may need to be
      revised for young breast cancer patients who smoke.

PMID- 8156489
TI  - Antiphospholipid syndrome associated with immunotherapy for patients with
      melanoma.
AB  - BACKGROUND: Immunotherapy for patients with cancer is associated with severe side
      effects, including the possible induction of autoantibodies. The latter was
      proven for antithyroid microsomal and antithyroglobulin antibodies. METHODS: This
      study was designed to evaluate antiphospholipid antibodies (APA) in 30 patients
      receiving three different forms of immunotherapy for disseminated melanoma using
      interleukin-2 (IL-2), alpha-interferon (alpha-interferon) or the combination of
      both. RESULTS: APA were detected in none of 18 patients treated with IL-2 alone,
      2 of 4 (50%) treated with alpha-interferon alone, and 3 of 8 (37.5%) treated with
      the combination of both. In the last group, increased concentrations of APA were
      observed, while the patients were still receiving alpha-interferon alone. APA
      levels were not detected in any of 10 patients with melanoma who were not treated
      with alpha-interferon or IL-2. In patients with increased APA, five of five
      (100%) had a prolongation of the partial thromboplastin time and 4 or five (80%)
      had deep venous thrombosis, which in one patient was followed by pulmonary
      embolism. CONCLUSIONS: The high incidence of therapy-induced elevated APA
      concentrations suggests that these should be carefully monitored in all patients
      receiving immunotherapy with alpha-interferon.

PMID- 8156490
TI  - Cutaneous malignant melanoma in south Sweden 1965, 1975, and 1985. A
      histopathologic review.
AB  - BACKGROUND: There is an increase in the incidence of cutaneous malignant melanoma
      (CMM) among white people throughout the world. In Sweden, a fivefold increase has
      been recorded since 1960, but the mortality is rising at a much lower rate. Tumor
      thickness is the single most important prognostic factor for primary melanoma.
      This study aimed to clarify whether the thickness of the tumor in invasive CMM
      decreased during the period 1965-1985. METHODS: This population-based study
      identified 574 cases of CMM, both invasive and noninvasive, in the South Swedish
      Health Care Region in 1965, 1975, and 1985. Twenty-six cases were excluded
      because the collection or evaluation of the material was not possible. The
      remaining 548 cases were reviewed histopathologically, and a diagnosis of
      invasive CMM was rejected in 71 cases. Eventually, 467 cases of invasive melanoma
      remained in our study (70 in 1965, 124 in 1975, and 273 in 1985). The level of
      invasion, tumor thickness, regression, ulceration, presence of inflammatory
      cells, benign naevus cells, and the site of presentation were studied. RESULTS:
      The study found neither a significant decrease of tumor thickness of invasive CMM
      nor changes in the level of invasion or proportion of ulcerated melanoma. A
      significantly higher proportion of melanoma tumors containing benign naevus cells
      was seen throughout the years (P < 0.05). Women had significantly fewer
      inflammatory cells in their tumors than did men (P < 0.01). As expected, the
      anatomical site of presentation showed a significant sex-related difference, with
      more tumors on the legs of female patients and more on the trunk of male patients
      (P < 0.001). CONCLUSIONS: There is a divergence between the rapidly increasing
      incidence and the slower increase in mortality of CMM. This cannot be explained
      by a removal of the melanoma at a thinner thickness. Differences between the
      sexes according to the tumor site and the increasing rate of CMM containing
      benign naevus cells could implicate changes in the tumor biology. Public
      education in Sweden concerning ultraviolet radiation and the connection with
      melanoma is fairly new and might not have any influence on this time period.
      Additional investigation is needed to clarify this matter.

PMID- 8156491
TI  - Preoperative and postoperative adjuvant combination chemotherapy for adults with
      high grade soft tissue sarcoma.
AB  - BACKGROUND: Patients with high grade soft tissue sarcoma greater than or equal to
      10 cm have a 3-year disease-free survival of approximately 30%. There is no
      convincing evidence, however, that postoperative adjuvant chemotherapy is
      beneficial. Preoperative chemotherapy has theoretical advantages over
      postoperative chemotherapy. METHODS: Twenty-nine evaluable patients with primary
      or recurrent high grade, nonmetastatic, soft tissue sarcoma were treated with two
      preoperative cycles of cyclophosphamide 500 mg/m2, doxorubicin 60 mg/m2, and DTIC
      1000 mg/m2 before definitive surgery and radiation. Clinical and radiologic
      assessment of response to chemotherapy was performed preoperatively, and the
      resected specimen was examined for treatment effects. Patients who did not
      progress during preoperative therapy were eligible to receive four additional
      cycles of chemotherapy. Disease-free and overall survival rates of study patients
      were compared with two cohorts of historic controls. RESULTS: Although subjective
      changes in the firmness of some tumors were observed, only one patient met the
      criteria for partial response (3%, 2-sided 95% confidence interval = < 1-17%).
      Intratumoral hemorrhage, cystic necrosis, and liquefaction were observed
      regularly, and three tumors were more than 90% necrotic. Toxicity of the
      chemotherapy was acceptable, but patients were reluctant to receive postoperative
      therapy. The median time free from distant metastasis was 28 months; median
      survival was 35 months. These results were not superior to the experience with no
      chemotherapy, or with postoperative doxorubicin. CONCLUSIONS: Adjuvant
      chemotherapy for patients with soft tissue sarcoma remains investigational. There
      is a strong rationale, however, for continued investigation of preoperative
      chemotherapy for high risk patients using doxorubicin and ifosfamide with colony
      stimulating factor support. Development of sensitive and specific methods to
      assess response to preoperative chemotherapy is needed.

PMID- 8156492
TI  - Influence of surgical margins on outcome in patients with preoperatively
      irradiated extremity soft tissue sarcomas.
AB  - BACKGROUND: Limb-sparing surgery for soft tissue sarcomas of the extremities may
      result in microscopically positive surgical margins. The consequences of these
      microscopically positive margins are unknown. We have analyzed the influence of
      surgical margins on local disease control and overall survival in patients with
      extremity soft tissue sarcomas who received preoperative radiation therapy
      followed by limb-sparing surgery. METHODS: Ninety-five consecutive patients with
      intermediate and high grade extremity sarcomas who received preoperative
      radiation therapy and limb-sparing surgery were identified from a soft tissue
      sarcoma data-base. The clinical outcome of 24 patients who had microscopically
      positive surgical margins was compared with that of 71 patients who had clear
      surgical margins. RESULTS: Multivariate statistical analysis revealed that
      patients with microscopically positive surgical margins or intraoperative tumor
      violation had an increased risk for local failure. High grade, large size, and
      intraoperative violation of the tumors were associated with decreased overall
      survival. However, neither the presence of a positive surgical margin nor the
      occurrence of a local failure adversely affected overall survival. CONCLUSIONS:
      Achieving negative surgical margins in patients with intermediate and high grade
      extremity sarcomas enhances local disease control but does not measurably improve
      overall survival. These data should be factored into patient management decisions
      in cases where the goal of achieving clear surgical margins requires amputation
      or the significant functional compromise of the extremity.

PMID- 8156493
TI  - Mammographically detected breast cancer. Nonpalpable is not a synonym for
      inconsequential.
AB  - BACKGROUND: Needle-guided breast biopsy has become a regularly recommended
      procedure to excise nonpalpable, questionable breast lesions detected by
      mammography. Whether cancers detected in this manner have a more favorable
      outcome than those detected by clinical examination is not clearly documented.
      METHODS: To address questions about the biology of mammographically detected
      cancer and likelihood of axillary node metastasis, as well as the accuracy of
      screening mammography, data from 3752 needle-guided breast biopsies and 1175
      nonpalpable breast cancers were reviewed. RESULTS: Between 1974 and 1992, 3752
      needle-guided biopsies were performed in 3441 women for nonpalpable breast
      lesions. Benign disease was disclosed in 2575 (68.7%) biopsies and malignancy in
      1175 (31.3%). Of 1130 malignancies, 61.8% were invasive carcinomas; 4.8% were
      microinvasive ductal carcinomas; 28.5% were ductal carcinomas in situ; and 4.8%
      were lobular carcinomas in situ. Axillary dissection in 558 patients with
      invasive carcinoma revealed that 27.1% had at least one positive axillary node.
      Of patients with invasive cancers presenting as nonpalpable calcifications alone,
      27.5% had at least one positive axillary node. CONCLUSIONS: More than one fourth
      of patients with nonpalpable, invasive cancer in this series had axillary node
      metastasis. Therefore, axillary dissection is an important treatment
      consideration for all patients with invasive carcinoma, despite technique of
      detection. Ductal carcinomas in situ detected as limited calcifications do not
      require axillary dissection. In this study, 31% of biopsies proved the presence
      of malignancy, an acceptable and appropriate benign-to-malignant ratio.

PMID- 8156494
TI  - Method of tumor detection influences disease-free survival of women with breast
      carcinoma.
AB  - BACKGROUND: Screening mammography provides the primary means of reducing breast
      cancer mortality. Clinical breast examination (CBE) and breast self-examination
      (BSE) may be complementary screening modalities enabling palpation of interval
      cancers and detection of tumors not visualized by mammography; however, their
      combined contribution to improving prognosis has not been evaluated adequately.
      METHODS: Disease-free survival was assessed in relation to method of tumor
      detection among 729 consecutive patients treated by mastectomy and axillary
      dissection for primary breast carcinoma between 1976 and 1978. RESULTS: Disease
      free survival at 10 years was significantly higher after detection by mammography
      (77% of 30 patients) or CBE (78% of 101 patients) compared to self-detection
      (64%). The hazard ratio of recurrence associated with clinical examination or
      mammography in contrast to self-detection was significantly reduced to 0.55 (95%
      CI, 0.37-0.81; P = 0.001). In addition, annual CBE, compared to less frequent
      clinical palpation, reduced the risk of recurrence controlling for detection
      modality (P = .03). In multivariate analyses, the method of detection and
      frequency of clinical breast examination remained statistically significant
      prognostic factors after controlling for number of screening mammograms, history
      of prior breast surgery, family history of breast cancer, and age at diagnosis.
      Differences in self-examination frequency were not associated with prognosis.
      CONCLUSIONS: Among patients diagnosed before widespread mammography screening,
      tumor detection by CBE was associated with a significant reduction in recurrence
      compared with detection by self-palpation. Improvement in the frequency and
      quality of CBE and BSE may enhance the contribution of these modalities to early
      detection, complementing the role of screening mammography in reducing breast
      cancer mortality rates.

PMID- 8156495
TI  - Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma?
AB  - BACKGROUND: Infiltrating lobular carcinomas (ILC) represent approximately 10% of
      all breast cancers. The literature is mixed regarding their prognosis when
      compared with infiltrating duct carcinomas (IDC). There are few data regarding
      the treatment of ILC with radiation therapy. METHODS: The clinical, pathologic,
      laboratory, and survival data of 161 patients with ILC were compared with the
      data of 1138 patients with IDC. RESULTS: ILCs were larger, more difficult to
      excise completely, and more difficult to diagnose clinically. All prognostic
      factors measured were more favorable for ILC. Nodal positivity for ILC was 32%,
      compared with 37% for IDC (P = 0.22). The 7-year disease-free Kaplan-Meier
      survival (DFS) was 74% for patients with ILC and 63% for patients with IDC (P <
      0.03). The 7-year breast cancer specific survival (BCSS) was 83% for patients
      with ILC and 77% for patients with IDC (P < 0.04). Selected patients with smaller
      lesions were treated with excision and radiation therapy. Patients with ILC
      treated with radiation therapy had a better DFS and BCSS than did patients with
      IDC treated with radiation therapy. CONCLUSIONS: ILCs often are homogeneous,
      small cell tumors of low nuclear grade. Their desmoplastic reaction may be absent
      or less marked than that of IDC, making them more difficult to palpate and to
      visualize mammographically. Despite this, they can be treated successfully with
      either mastectomy or excision and radiation therapy.

PMID- 8156496
TI  - Observations on tumor and metastatic suppressor gene status in endometrial
      carcinoma with particular emphasis on p53.
AB  - BACKGROUND: Genetic changes in the development of endometrial carcinoma have not
      been characterized, and little is known of tumor or metastatic suppressor gene
      status in these malignancies. The current study on endometrioid carcinoma was
      undertaken to examine the status of two tumor suppressor genes that frequently
      have been found to be altered in human malignancies (the p53 gene and the
      retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic
      suppressor gene, nm23-H1. METHODS: The status of the p53 gene was studied by
      immunohistochemistry of formalin-fixed paraffin-embedded biopsy samples from 72
      patients with atypical endometrial hyperplasia or endometrioid carcinoma who
      underwent hysterectomy immediately after biopsy and from 5 patients with benign
      endometria. A search for loss of heterozygosity (LOH) of the nm23 gene after DNA
      extraction from frozen tissues and hybridization with nm23-H1 cDNA specific probe
      was made in 10 endometrial carcinomas. Rb gene status was evaluated by image
      analysis quantification of immunoreactive retinoblastoma protein in frozen
      sections of 10 carcinomas and 2 benign endometria. RESULTS: p53 expression was
      low in all benign endometria, but high expression was found in 2 (15%) of 13
      atypical hyperplasias and in 23 (39%) of 59 carcinomas. High levels of p53
      expression in endometrioid carcinoma correlated with the spread of disease
      outside of the uterus and by logistic regression, the presence of squamous
      differentiation, nuclear grade, and high p53 expression in the biopsy all
      independently correlated with spread of disease outside of the uterus. Although 7
      of the 10 carcinomas studied were informative, LOH for the nm23 gene was not seen
      in any, including a site of metastasis. Rb protein expression in endometrial
      carcinoma was similar to expression in benign endometria. CONCLUSIONS: Although
      this study found no evidence of nm23-H1 gene alteration or alterations in Rb
      protein levels in endometrial carcinoma, high expression of p53 protein was
      sporadically identified in biopsy specimens of atypical hyperplasia and
      frequently found in endometrioid carcinomas. Determination of p53 expression in
      combination with the presence or absence of squamous differentiation and nuclear
      grade in biopsy material may help predict spread of endometrioid carcinoma
      outside the uterus and facilitate therapeutic planning before hysterectomy.

PMID- 8156497
TI  - Are CASA and CA125 concentrations in peripheral blood sourced from peritoneal
      fluid in women with pelvic masses?
AB  - BACKGROUND: The Cancer associated serum antigen (CASA) and CA125 assays used in
      the management of ovarian cancer measure distinct high molecular weight
      glycoproteins. The mechanisms of secretion of these molecules into the peripheral
      circulation are not clearly understood. METHODS: Concentrations of CASA and CA125
      were assessed in peripheral blood, blood from veins draining ovarian and omental
      tumors, and peritoneal fluid in 20 women with pelvic masses. RESULTS: There was a
      near perfect correlation between peripheral vein and ovarian vein concentrations
      for both markers; concentrations in omental veins were higher than in peripheral
      veins in only a small proportion of cases, whereas the concentration in
      peritoneal fluid was universally much higher than in blood. CONCLUSIONS: These
      studies suggest a similar route of entry into the peripheral circulation and a
      similar half-life for these glycoproteins. These data provide no support for the
      hypothesis that a significant contribution to CA125 concentrations comes from
      peritoneal release by mesothelial cells rather than tumor cells, because the
      relative CA125 concentrations between compartments were similar to those of CASA
      within patients. The lack of a gradient between CASA levels in peripheral blood
      and tumor draining veins suggests that the CASA half-life is much longer than
      that predicted in animal studies. CA125 and CASA in peripheral blood are probably
      derived from markers secreted into peritoneal fluid and lymph, rather than
      directly into the bloodstream.

PMID- 8156498
TI  - Descriptive epidemiology of prostate cancer in metropolitan Detroit.
AB  - BACKGROUND: The incidence of prostate cancer among US men increased more than
      five times over the past six decades. Black men in the United States now have the
      world's highest reported incidence of prostate cancer. The authors examined the
      distribution of prostate cancer in metropolitan Detroit from 1973 to 1989.
      METHODS: Cases collected by the Metropolitan Detroit Cancer Surveillance System
      were used to calculate standardized age-adjusted rates of prostate cancer by race
      and stage and standardized age-specific rates for the age groups 60-69, 70-79 and
      80 years and older. Over 24,000 cases involving black and white men were
      analyzed. RESULTS: During 1973 to 1989, age-adjusted rates of prostate cancer
      diagnosed among white men doubled from 54.3 to 109.9 per 100,000 and those among
      black men increased by nearly 40% from 106.9 to 148.6 per 100,000. Average annual
      increases in age-adjusted rates for white and black men were 4.4 and 2.3%,
      respectively. CONCLUSIONS: Age-adjusted rates of prostate cancer diagnosed among
      white men increased more rapidly than rates among black men during 1973 to 1989.
      The more rapid increase in cases diagnosed in white men may represent differences
      in access and exposure to early detection and treatment practices. Improved
      efforts toward earlier detection are needed, especially among black men.

PMID- 8156499
TI  - Clinical variables which serve as predictors of cancer-specific survival among
      patients treated with radical cystectomy for transitional cell carcinoma of the
      bladder and prostate.
AB  - BACKGROUND: Studies have demonstrated conclusively that the stage and grade of
      transitional cell tumors at presentation are major determinants of survival for
      those with the disease in the bladder and prostate. The authors initiated a
      review of 531 patients with transitional cell carcinoma of the bladder and
      prostate treated with radical cystectomy between 1969 and 1990 to identify other
      clinical features predictive of cancer-specific survival. MATERIALS AND METHODS:
      Inpatient and clinical medical records were analyzed for age, race, gender,
      clinical T stage, medical history, and presenting symptoms and signs, and
      admission laboratory values were correlated with the patient's cancer-specific
      outcome. Both univariate and multivariate analyses of the various clinical
      factors were performed to identify variables predictive of cancer-specific
      survival. RESULTS: Univariate analysis indicated that clinical T classification,
      preoperative hemoglobin, tumor grade, irritative voiding symptoms, age,
      preoperative creatinine, obstructive hydronephrosis on preoperative excretory
      urography, a history of bladder tumors or nephrouretectomy for transitional cell
      cancer, prior urinary tract infections, prior pelvic irradiation, and obstructive
      symptoms were all predictive of poor cancer-specific survival. Multivariate
      analysis demonstrated that higher clinical T classification (T2, T3a, T3b, T4
      versus Ta, Tis, T1) (P < 0.001), increasing age (< 65 years versus > or = 65
      years) (P < 0.001), the presence of irritative voiding symptoms (P = 0.01),
      higher tumor grade, lower preoperative hemoglobin level (< or = 12 gm/dl versus >
      12 gm/dl) (P < 0.001), higher preoperative creatinine level (> or = 1.5 mg/dl
      versus < 1.5 mg/dl) (P = 0.002), a history of nephroureterectomy for transitional
      cell cancer (P = 0.016), and a history of pelvic irradiation (P = 0.002) were all
      predictive of poor cancer-specific survival. CONCLUSIONS: Although clinical T
      classification and tumor grade remain the best predictors of survival in patients
      with transitional cell carcinoma of the bladder or prostate, clinical variables
      such as age, preoperative creatinine and hemoglobin levels, a history of
      nephroureterectomy or pelvic irradiation, and irritative voiding symptoms at
      presentation may provide additional prognostic information independent of tumor
      grade and stage.

PMID- 8156500
TI  - Long survival in patients with acquired immune deficiency syndrome-related
      primary central nervous system lymphoma.
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is the most common
      brain tumor occurring in patients with acquired immune deficiency syndrome
      (AIDS). After diagnosis of PCNSL, the median survival time is 2-5 months with
      treatment with whole brain irradiation (WBI). METHODS: Four (of approximately 40)
      patients with AIDS and PCNSL seen by the University of California, San Diego
      (UCSD) Neuro-Oncology service were treated with multimodal therapy, including WBI
      with hydroxyurea, followed by 3 cycles of procarbazine/lomustine/vincristine
      (PCV) chemotherapy. RESULTS: Survival after tumor diagnosis ranged from 11 to 16
      months, with a median of 13.5 months. CONCLUSION: Selected patients with AIDS and
      PCNSL may have long survival when treated with multimodal therapy.

PMID- 8156501
TI  - Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in
      patients receiving adoptive immunotherapy. Augmentation with cyclophosphamide and
      correlation with response.
AB  - BACKGROUND: The adoptive transfer of interleukin-2 (IL-2)-cultured tumor
      infiltrating lymphocytes (TIL) can cause tumor regression in patients with
      metastatic melanoma. METHODS: Thirty-eight patients with metastatic melanoma
      receiving high dose IL-2 and TIL were studied for the ability of autologous 111In
      labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and
      biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL
      infusion in 27 treatment courses. RESULTS: Tumor localization by 111In-labeled
      TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a
      univariate analysis of factors influencing TIL traffic, cyclophosphamide
      administration was significantly associated with the ability to localize tumor by
      radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) treatment courses
      given with cyclophosphamide demonstrated tumor localization, compared with only 5
      of 12 (41.7%) treatment courses without cyclophosphamide. In addition, patients
      whose 111In-labeled TIL imaged their tumor received significantly more TIL than
      did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of
      111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and
      0.0004% injectate/gram of tissue, respectively; P2 = < 0.001). The median tumor
      to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5%)
      patients who had tumor localization by scan had a clinical response, whereas no
      responses were noted in 12 patients whose tumors were not imaged (P2 = 0.022).
      CONCLUSIONS. Localization in tumor may be important in the mechanism of TIL
      antitumor activity because no clinical responses were seen in patients who did
      not have their tumors imaged with 111In-TIL. Cyclophosphamide administration
      before TIL and IL-2 therapy and the administration of large numbers of TIL appear
      to improve the frequency of TIL localization to tumor.

PMID- 8156502
TI  - Four varied cases of intravascular lymphomatosis and a literature review.
AB  - BACKGROUND: Intravascular lymphoma (IVL) is an uncommon malignancy defined
      pathologically by neoplastic proliferation of lymphoid cells within the lumens of
      capillaries, small veins, and arteries, with little or no adjacent parenchymal
      involvement. The nature of IVL has been the subject of considerable controversy.
      Recent immunohistochemical studies have demonstrated clearly that the tumors bear
      the immunophenotype of neoplastic lymphoid cells of either B-cell or T-cell
      lineage. IVL commonly affects the central nervous system, resulting in
      progressive dementia and multiple neurologic deficits; skin is the second most
      common site of involvement, in the form of cutaneous plaques and nodules.
      METHODS: In a retrospective review of all cases of non-Hodgkin's lymphoma seen at
      our institution, four cases of IVL were identified. Case 1 was fixed in
      methacarin, and Cases 2-4 were fixed in 10% formalin. Standard fixation, tissue
      processing, sectioning, and hematoxylin and eosin staining were used.
      Immunophenotypic studies were performed using a modified avidin-biotin complex
      technique. The specimen in Case 1 was stained by Giemsa stain using standard
      techniques. RESULTS: Four cases of IVL are presented. One patient experienced
      hypoxemia and fevers of unknown origin; the second, dementia and a vasculitislike
      illness; the third rapidly progressive dementia, nonlocalizing neurologic
      deficits, and panhypopituitarism; the fourth Kaposi-like skin lesions. Case 1
      relapsed shortly after completing chemotherapy. Salvage chemotherapy has yielded
      good initial response. Autopsy findings in cases 2, 3 and 4 confirmed IVL in many
      vessels, including the brain, lung, liver, heart, gastrointestinal tract,
      glomerulus, central nervous system, and skin. Malignant lymphoid cells marked as
      B-cells in all cases. CONCLUSIONS: Unusual and interesting clinical presentations
      may occur in patients with IVL. The medical literature indicates that few cases
      are diagnosed ante mortem. Although isolated patients may respond favorably to
      chemotherapy, most will deteriorate rapidly and the diagnosis of IVL not
      contemplated until necropsy.

PMID- 8156503
TI  - Clonal chromosomal abnormalities in osteofibrous dysplasia. Implications for
      histopathogenesis and its relationship with adamantinoma.
AB  - BACKGROUND: The pathogenesis of osteofibrous dysplasia, a rare fibroosseous
      lesion occurring almost exclusively in the tibia of children younger than 10
      years of age, is not known. One theory is that osteofibrous dysplasia results
      from excessive resorption of bone with fibrous repair of the defect.
      Alternatively, osteofibrous dysplasia has been considered a congenital lesion or
      a variant of fibrous dysplasia. It has been hypothesized that osteofibrous
      dysplasia is a secondary reactive process to adamantinoma. Cytogenetic analysis
      is one form of investigation that has been instrumental in determining the origin
      of many disorders. METHODS: Short-term cultures of two separate osteofibrous
      dysplasia specimens (approximately 1 year apart) from the tibia of an 11-year-old
      boy and 2 separate specimens (approximately 2 years apart) from the tibia of a 16
      year-old boy were cytogenetically examined using standard procedures.
      Additionally, fluorescence in situ hybridization (FISH) studies were performed on
      uncultured cells of both specimens of the first patient using an alpha-satellite
      probe for chromosome 12. RESULTS: Cytogenetic and FISH analysis revealed trisomy
      12 in both specimens of the first patient. Trisomy for chromosomes 7, 8, and 22
      was seen in both specimens of the second patient. CONCLUSIONS: Osteofibrous
      dysplasia has not previously been subjected to cytogenetic analysis. Trisomy 7
      and 12, however, have been reported in a clonally aberrant adamantinoma,
      potentially providing further support for a relationship between these two
      lesions. Most importantly, these findings demonstrate a clonal and possibly
      neoplastic origin for osteofibrous dysplasia of long bone.

PMID- 8156504
TI  - Relapse of acute lymphoblastic leukemia in the inferior rectus muscle of the eye.
AB  - BACKGROUND: Extramedullary involvement of acute lymphoblastic leukemia (ALL) in
      sites outside the central nervous system (CNS) or testes is rare and may signal a
      refractory form of leukemia. METHODS: The authors describe a child with ALL who
      experienced a relapse involving the inferior rectus muscle of the eye. This
      patient had been treated with a bone marrow transplant for previous bone marrow
      and ovarian relapse. RESULTS: The patients had a pre-B ALL with a t(1;19)
      chromosomal translocation and previously had experienced relapse during therapy.
      At the time of the muscle relapse, she had pancreatomegaly consistent with
      leukemic infiltration but no CNS or bone marrow disease. CONCLUSIONS: Relapse of
      ALL in unusual sites may indicate disease that is particularly difficult to
      eradicate. Factors in addition to age and leukocyte count at diagnosis determined
      risk. Additional research is needed to define these factors and develop more
      effective therapy.

PMID- 8156505
TI  - Recurrent renal salt wasting in a child treated with carboplatin and etoposide.
AB  - BACKGROUND: Nephrotoxicity of carboplatin is rare, especially in children with
      normal renal function. A 3-year-old boy had localized esthesioneuroblastoma and
      received 2 courses of carboplatin (200 mg/m2/day during a 1-hour infusion for 3
      consecutive days) associated with etoposide (150 mg/m2/day after carboplatin).
      Because of a good tumor response, a second course was given 21 days later.
      Complete surgical excision and local irradiation were performed. However, the
      tumor recurred a few months later, and the patient subsequently died of the
      disease. METHODS: Renal function initially was assessed by standard baseline
      chemistry and technetium-panetetic acid (Tc-DTPA) clearance. Follow-up included
      ionic controls and tubular exploration during the episodes of hyponatremia.
      RESULTS: Hyponatremia occurred 4 days after completion of the first course and
      resolved after intravenous supplementation. It recurred 20 days after the second
      course despite salt and magnesium prehydration and posthydration and resolved 17
      days later. No glomerular dysfunction was noticed. The association of urinary
      bicarbonate loss with elevated N-acetyl-beta-glucosaminidase suggested a proximal
      tubular damage. CONCLUSIONS: Standard doses of carboplatin may lead to recurrent
      renal salt wasting in children with initially normal renal function.

PMID- 8156506
TI  - Apoptosis. Its significance in cancer and cancer therapy.
AB  - Apoptosis is a distinct mode of cell death that is responsible for deletion of
      cells in normal tissues; it also occurs in specific pathologic contexts.
      Morphologically, it involves rapid condensation and budding of the cell, with the
      formation of membrane-enclosed apoptotic bodies containing well-preserved
      organelles, which are phagocytosed and digested by nearby resident cells. There
      is no associated inflammation. A characteristic biochemical feature of the
      process is double-strand cleavage of nuclear DNA at the linker regions between
      nucleosomes leading to the production of oligonucleosomal fragments. In many,
      although not all of the circumstances in which apoptosis occurs, it is suppressed
      by inhibitors of messenger RNA and protein synthesis. Apoptosis occurs
      spontaneously in malignant tumors, often markedly retarding their growth, and it
      is increased in tumors responding to irradiation, cytotoxic chemotherapy, heating
      and hormone ablation. However, much of the current interest in the process stems
      from the discovery that it can be regulated by certain proto-oncogenes and the
      p53 tumor suppressor gene. Thus, c-myc expression has been shown to be involved
      in the initiation of apoptosis in some situations, and bcl-2 has emerged as a new
      type of proto-oncogene that inhibits apoptosis, rather than stimulating mitosis.
      In p53-negative tumor-derived cell lines transfected with wild-type p53,
      induction of the gene has, in rare cases, been found to cause extensive
      apoptosis, instead of growth arrest. Finally, the demonstration that antibodies
      against a cell-surface protein designated APO-1 or Fas can enhance apoptosis in
      some human lymphoid cell lines may have therapeutic implications.

PMID- 8156507
TI  - Esophageal morphology from Linxian, China. Squamous histologic findings in 754
      patients.
AB  - BACKGROUND: Linxian, China, has one of the highest rates of esophageal cancer in
      the world. Other authors have described high prevalences of histologic
      esophagitis, atrophy, and dysplasia in Linxian and have suggested that these
      findings may represent precancerous lesions in this population. In 1987, a new
      endoscopic survey allowed the authors to make an independent study of esophageal
      histology in Linxian. METHODS: There were 1567 satisfactory squamous esophageal
      biopsies available from 754 patients. These biopsies were classified as normal,
      atrophy, acanthosis, esophagitis, squamous dysplasia, or squamous cancer.
      RESULTS: Classified by their worst diagnosis, 56.5% of the 754 patients had
      normal mucosa, 0.0% atrophy, 11.5% acanthosis, 4.6% esophagitis, 22.7% squamous
      dysplasia, and 4.6% squamous cancer. CONCLUSIONS: The results show a different
      distribution of esophageal squamous diagnoses than has been reported previously
      from this population. The authors believe that the major reason for this
      discrepancy was differences in histologic criteria. In this survey, seemingly
      small differences in criteria could cause large differences in apparent disease
      prevalence; this was especially true for esophagitis. By the criteria used in
      this study, histologic esophagitis and atrophy are uncommon findings in Linxian,
      raising questions about their significance as precursor lesions of esophageal
      cancer in this population.

PMID- 8156508
TI  - Gastric mucosal injury after hepatic arterial infusion chemotherapy with
      floxuridine. A clinical and pathologic study.
AB  - BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) of liver metastases of
      colon cancer with an implantable pump is associated with liver and
      gastrointestinal complications. METHODS: The authors retrospectively studied the
      clinical features and gastric histopathology of nine patients who received HAIC
      and had gastritis develop and in whom biopsy specimens were available. RESULTS:
      Gastritis was heralded in these patients by epigastric pain and tenderness,
      nausea, vomiting, weakness, and anorexia. In seven patients, 18 gastric ulcers
      were endoscopically detected. Mucosal damage developed despite prophylactic
      antiulcer therapy and healed only upon cessation of HAIC. These observations
      suggest that the predominant drug given, floxuridine, was the responsible toxic
      agent. Seventeen biopsy specimens were reviewed, and all exhibited varied
      histologic evidence of inflammation, reactive glandular changes, and cell
      necrosis. These mucosal changes were present even in tissues obtained from
      patients without ulcers. In addition, floxuridine-induced glandular atypia was
      noted in eight biopsy samples from six patients. The crowded glands were
      distorted and lined by large cells that included bizarre forms with pleomorphic
      nuclei. CONCLUSIONS: Gastric injury in HAIC appeared analogous to the general
      features encountered in reactive gastritis resulting from chemical irritants. The
      glandular atypia is peculiar to HAIC, and although the changes were
      morphologically alarming, in this clinical situation care should be exercised not
      to interpret floxuridine-induced atypia as carcinoma.

PMID- 8156509
TI  - Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of
      gastric cancer. Final results of a randomized controlled study.
AB  - BACKGROUND: Continuous hyperthermic peritoneal perfusion (CHPP) with a solution
      that contained 10 micrograms/ml mitomycin C was devised initially as a method for
      intraperitoneal thermochemotherapy. The authors conducted a randomized clinical
      trial to evaluate the efficacy of CHPP as a prophylactic treatment for prevention
      of peritoneal recurrence of gastric cancer with serosal invasion. METHODS:
      Between January 1983 and October 1986, 82 patients with gross serosal invasion
      but no gross peritoneal metastasis were divided by random sampling into two
      groups before undergoing potentially curative surgery for gastric cancer: 42
      patients were scheduled to receive CHPP, whereas 40 were not scheduled to receive
      this treatment. CHPP was administered immediately after closing the abdomen after
      gastric resections while the patients were still on the operating table under
      general anesthesia. RESULTS: The 5-year survival rate (64.2%) of patients in the
      CHPP group was higher than that (52.5%) of patients in the control group although
      the difference was not significant. Of several patterns of cancer recurrence,
      peritoneal recurrence was more frequent in the control group than in the CHPP
      group. The mortality rate from peritoneal recurrence in the case of patients in
      the CHPP group was much lower than that of patients in the control group (P =
      0.0854). CHPP did not induce anastomotic breakdown or chemical peritonitis after
      surgery. CONCLUSIONS: The results indicate that CHPP is effective in preventing
      peritoneal recurrence of gastric cancer with serosal invasion, which is highly
      likely to reappear in the peritoneum.

PMID- 8156510
TI  - Gastric carcinoids. An immunohistochemical and clinicopathologic study of 104
      patients.
AB  - BACKGROUND: Gastric carcinoids are uncommon, and are unlike carcinoids at other
      gastrointestinal sites, clinically and pathologically. METHODS: The authors
      studied specimens from 104 patients with gastric carcinoid, with study emphasis
      being placed on pathologic features, immunohistochemistry, clinical associations,
      and prognostic factors. RESULTS: The average age of the 47 male patients and 57
      female patients was 61 years. Twenty-seven patients had chronic atrophic
      gastritis, 12 had pernicious anemia, and 6 had hypergastrinemia; no patient had
      carcinoid syndrome. Most of the tumors were confined to the mucosa and submucosa.
      Lymph node metastases were present in only one patient. The tumors were
      argyrophilic in 84% and argentaffin in 14%. Chromogranin tested positive in all
      patients; serotonin was detected in one-third; other hormones were much less
      common. Gastrin-positive tumors were antral. Of the 62 patients with follow-up,
      44 were alive without disease, 4 were alive with disease, and 14 were dead (4
      died of carcinoid-related disease). None of the deceased had pernicious anemia or
      hypergastrinemia. The tumors in patients with a fatal outcome were 2 cm or
      larger. CONCLUSION: Gastric carcinoids generally are indolent tumors,
      particularly when associated with pernicious anemia or hypergastrinemia or when
      smaller than 2 cm. Chromogranin is the most sensitive marker.

PMID- 8156511
TI  - Lymph node metastasis from carcinoma of the distal one-third of the stomach.
AB  - BACKGROUND: A detailed and thorough pathoanatomic study of lymph node (LN)
      metastases of adenocarcinoma of the distal one-third of the stomach is lacking.
      METHODS: From December 1987 to March 1992, 190 patients who underwent radical
      gastrectomy was analyzed. All LN were dissected and labeled according to the
      Japanese General Rules for the Gastric Cancer Study. RESULTS: A total of 7052 LN
      with average of 37.1 per specimen were removed. LN metastases were encountered in
      121 patients (63.7%). The most frequent LN metastases were perigastric, above
      common hepatic artery, along left gastric artery, and hepatoduodenal ligament.
      The incidence of LN metastasis varied and was highest when tumor was located
      close to either curvature and extended to duodenum or midbody. The high incidence
      of LN metastases in the hepatoduodenal ligament was a unique pathologic feature
      of lower stomach cancer (P = 0.0012). Univariate and multivariate analysis
      revealed that depth of cancer invasion was the only factor related to LN
      metastases. CONCLUSIONS: Cancer in the distal one-third of the stomach had a high
      incidence of LN metastasis to hepatoduodenal ligament nodes (No. 12). The LN
      metastasis is correlated with depth of cancer invasion.

PMID- 8156512
TI  - Mortality in young first-degree relatives of patients with familial adenomatous
      polyposis.
AB  - BACKGROUND: Mortality and cancer deaths among young family members of patients
      with familial adenomatous polyposis (FAP) were investigated. METHODS: The
      subjects were 1764 members of 628 families with FAP registered at the authors'
      Polyposis Registry. They consisted of first-degree relatives of patients with
      FAP, excluding the propositus. These 1764 subjects were born between 1960 and
      1978. Their survival times and causes of death were certified mainly by the
      National Family Registry and death certificates. Relative mortality rates were
      calculated based on the calendar year, age sex, and cause-specific death rate of
      Japanese people in the Vital Statistics, (Ministries of Health and Welfare,
      Japan. Vital statistics, Japan, Vol. 1960-1990. Tokyo: Statistics and Information
      Department, Minister's Secretariat, Ministry of Health and Welfare.) 1960-1990,
      Japan. RESULTS: There were 69 deaths before the age of 25 years. Deaths from
      malignant tumor were observed in 20 cases. Overall relative mortality rate in the
      subject group younger than age 20 years was 1.48. Relative cancer mortality in
      the age group between 1 and 4 years was significantly higher, because the
      relative mortality from hepatoblastoma in this age group was 176. Relative cancer
      mortality rate was significantly higher among males 15-19 years of age (15.4) and
      20-24 years of age (male, 33.3; female, 150) due to colorectal cancer.
      CONCLUSIONS: Hepatoblastoma was a specific cancer in the 1- to 4-year-old age
      group in first-degree family members of patients with FAP. The incidence of
      colorectal cancer considerably increased, starting around the age of 20 years.

PMID- 8156513
TI  - Pathologic determinants of survival associated with colorectal cancer with lymph
      node metastases. A multivariate analysis of 579 patients.
AB  - BACKGROUND: Patients with colorectal carcinoma found to have regional lymph node
      metastases after curative resection form a large and prognostically diverse
      group. This study aims to determine which pathology variables have independent
      prognostic effects. METHODS: The data from the 579 patients used in this analysis
      were collected prospectively during a period of 21.5 years. The patients were
      from one institution, and the pathologic documentation was standardized. Patient
      follow-up ranged between 6 months and 21.5 years. Survival analysis was by the
      Kaplan-Meier method. Multivariate models were examined using Cox proportional
      hazards regression. RESULTS: On univariate analysis, eight pathology variables
      had a significant association with survival. Six of these variables showed
      significant independent effects on survival on multivariate analysis. In
      diminishing potency, these variables were: apical lymph node involvement; spread
      involving a free serosal surface; invasion beyond the muscularis propria;
      location in the rectum; venous invasion; high tumor grade. Significant
      independent effects also were shown for patient age and gender. The number of
      involved lymph nodes added no significant independent prognostic information.
      CONCLUSION: Six pathology variables have been identified that act independently
      in determining the survival of patients with colorectal carcinoma and lymph node
      metastases. The most potent of these variables, apical lymph node involvement,
      was used by Dukes to subclassify Stage C tumors. Another variable, direct spread
      beyond the muscularis propria, defines the Astler-Coller subclassification. It is
      recommended that all six independent variables be included in any future protocol
      for stratifying this prognostically diverse group of patients.

PMID- 8156514
TI  - Measurement of quality of life in patients with lung cancer in multicenter trials
      of new therapies. Psychometric assessment of the Lung Cancer Symptom Scale.
AB  - BACKGROUND: This study continued the development and psychometric testing of the
      Lung Cancer Symptom Scale (LCSS), a disease- and site-specific instrument
      primarily measuring the physical and functional dimensions of quality of life for
      individuals with lung cancer. The instrument contains two scales, one for
      patients and a counterpart for health professionals as observers. METHODS:
      Feasibility, reliability, construct validity, and criterion-related validity were
      evaluated with 207 patients with non-small cell lung cancer (NSCLC) from six
      cancer centers. Within an interview with an observer, patients completed part of
      a battery of instruments by self-report and were interviewed for the remaining
      measures. Observers also completed measures after the interview. RESULTS:
      Feasibility, reliability, and validity were well supported for this lung cancer
      population. Feasibility was demonstrated by patient and staff compliance in
      completion at all six cancer centers. Internal consistency was good, with
      coefficient alphas of 0.82 for the patient scale and 0.75 for the observer scale.
      Construct validity was supported by 1. contrasted groups approach: regression
      lines (with 95% confidence bands) were obtained between the Karnofsky performance
      scale (KPS) and each of the two LCSS scales; 2. as a refinement, relationship
      testing: significant correlations between the LCSS and KPS for each item (except
      hemoptysis for the patient scale); and 3. multitrait-multimethod approach: good
      reliability (alphas ranging from 0.75 to 0.93), good convergent validity for the
      two LCSS scales (r = 0.77), and a good discriminant validity pattern from the
      Brief Symptom Inventory (BSI). Criterion-related validity with relevant gold
      standard measures (American Thoracic Society Questionnaire [ATS] and McGill Pain
      questionnaire, KPS, Profiles of Mood States [POMS], and Sickness Impact Profile
      [SIP]) was supported with significant correlations (0.40-0.67 for the LCSS
      patient scale; 0.54-0.65 for the LCSS observer scale). CONCLUSIONS: These
      psychometric properties demonstrate that the LCSS patient and observer scales are
      feasible, reliable, and valid quality of life measures that are ready for
      research and clinical use with lung cancer populations.

PMID- 8156515
TI  - Antifungal prophylaxis during remission induction therapy for acute leukemia
      fluconazole versus intravenous amphotericin B.
AB  - BACKGROUND: Fungal infection is a frequent and often fatal complication in
      patients undergoing remission induction therapy for acute leukemia. Although
      candidiasis is the most common infection, mold infections are increasing in
      frequency. Fluconazole (FLU) is a new antifungal agent that has been used
      successfully to treat Candida infections and has modest activity against
      aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have
      been considered effective as prophylaxis in these patients. This study was
      designed to compare the efficacy and toxicity of these agents as antifungal
      prophylaxis. METHODS: Adults with acute leukemia undergoing remission induction
      chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB
      (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim
      sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis
      was continued until the patient achieved complete remission or was treated for 8
      weeks without antileukemic response. Prophylaxis was discontinued if the patient
      experienced a possible or proven fungal infection or a serious toxicity. RESULTS:
      Overall, 58% of the 36 patients assigned to AMB successfully completed
      prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05).
      Proven, probable, or possible fungal infections occurred in 31% and 17% of the
      patients, respectively. The risk of discontinuing prophylaxis due to fungal
      infection or toxicity increased with time in the study and was significantly
      greater for AMB (P = 0.02). CONCLUSIONS: At the dose used in this study, AMB was
      no more effective and was more toxic than FLU for prophylaxis of fungal
      infections in patients undergoing remission induction chemotherapy for acute
      leukemia.

PMID- 8156516
TI  - Timed-sequential high-dose cyclophosphamide and vincristine in the treatment of
      multiple myeloma.
AB  - BACKGROUND: This study was designed to examine the efficacy and toxicity of high
      dose cyclophosphamide (CY), and to evaluate the potential added effect of
      vincristine (VCR) given at a theoretic time of malignant cell stimulation in a
      group of patients with multiple myeloma, refractory to or relapsing after,
      treatment with standard doses of chemotherapy. METHODS: Patients were randomly
      assigned to receive CY 2400 mg per M2 as a single-day dose and VCR 1.4 mg per M2
      given on Day 1 or Day 9 after the CY. RESULTS: There were 108 cases suitable for
      analysis. No difference in objective response (17.6%, 23.5%), subjective
      response, remission duration, or survival was observed in the two treatment arms.
      CONCLUSIONS: The authors conclude that a single, high dose of cyclophosphamide is
      more toxic and provides equal or less response than the equivalent dose given
      over 4 consecutive days and that no improved effect was detected using timed
      sequential therapy with VCR.

PMID- 8156517
TI  - Clinical and histologic involvement of regional lymph nodes in malignant
      melanoma. Adjuvant vindesine improves survival.
AB  - BACKGROUND: This report is a study of prognostic factors, including adjuvant
      chemotherapy, that influence survival of patients with malignant melanoma who
      have clinical and pathologic involvement of regional lymph nodes. METHODS: A
      total of 169 evaluable patients with malignant melanoma metastatic to regional
      lymph nodes were registered consecutively and prospectively between June 1977 and
      December 1986 in the computerized data base of the melanoma registry at
      Westminster Hospital. Eighty-seven of these patients received adjuvant
      chemotherapy with vindesine after resection of palpable metastatic lymph nodes,
      and 82 had no systemic treatment after surgery. All were followed up for at least
      2 years (median, 8 years) after involvement of regional lymph nodes was noted or
      until death. Statistical analyses included simple life-table comparisons,
      unadjusted for covariates. In addition, Breslow's thickness, ulceration of the
      primary lesion, its anatomical location, number of regional lymph nodes
      histologically involved, dissection site, patient age and sex, and adjuvant
      vindesine therapy were included as covariates in Cox regression models. RESULTS:
      The disease-free interval (P = 0.0001), time to dissemination from lymph node
      metastases (P < 0.0001), survival time after lymph node dissection (P = 0.0227)
      and overall survival time after initial diagnosis of malignant melanoma (P =
      0.0095, log-rank chi-square test) were superior for the 87 patients who received
      adjuvant chemotherapy with vindesine. Cox regression analysis confirmed adjuvant
      vindesine as a highly significant variable influencing all of these outcomes,
      including overall survival time after first diagnosis (P = 0.003). CONCLUSIONS:
      The apparent effect of adjuvant vindesine on overall survival in this study is
      large (hazard ratio, 0.52) and highly statistically significant. Adjuvant
      vindesine therapy merits consideration for malignant melanoma metastatic to
      regional lymph nodes. However, these results observed in concurrent, but
      nonrandomized, patients clearly require confirmation.

PMID- 8156518
TI  - Phase II study on neoadjuvant hyperthermic-antiblastic perfusion with doxorubicin
      in patients with intermediate or high grade limb sarcomas.
AB  - BACKGROUND: Locoregional control of soft tissue sarcomas of the limbs is achieved
      generally using a multidisciplinary approach consisting of conservative surgery
      combined with radiation therapy, intraarterial chemotherapy, or hyperthermic
      antiblastic perfusion (HAP). Before surgery, HAP seems to be the more suitable
      tool in decreasing tumor mass and allowing limb-sparing surgery. The authors' aim
      was to ascertain the activity of HAP with doxorubicin against intermediate or
      high grade limb tumors. METHODS: In 23 patients with limb sarcomas (2 patients
      International Union Against Cancer Stage IIA, 4 stage IIB, 1 stage IIIA, 11 stage
      IIIB, and 5 stage IVB) doxorubicin was administered via HAP 4-6 weeks before
      surgery. The drug (bolus, 0.7-1.4 mg/kg) was perfused for 60 minutes with a tumor
      temperature of at least 40.5 degrees C (range, 40.5-42.6 degrees). Tumor necrosis
      was then assessed radiologically and pathologically. RESULTS: Systemic toxicity
      was hematologic grade (G) 2 in 2 patients, gastrointestinal (hepatic) in 6, G1 in
      2, G2 in 3, and G3 in 1; 2 patients had alopecia; locoregional toxicity (graded
      according to Wieberdink) was G1 or G2 in 18, G3 in 4, and G4 in 1. Tumor necrosis
      was more than 50% in 17 patients (74%). Limb-sparing surgery was feasible in 20
      patients (91%). At present, 14 patients are alive. Six had local recurrences, and
      eight had distant metastases. CONCLUSIONS: Our findings show that HAP with
      doxorubicin is an active and well-tolerated procedure within a multidisciplinary
      approach to treatment of limb sarcomas.

PMID- 8156519
TI  - p53 gene mutations and steroid receptor status in breast cancer.
      Clinicopathologic correlations and prognostic assessment.
AB  - BACKGROUND: There is increasing evidence linking development and progression of
      cancer to an accumulation of mutations at the genomic level. The most frequently
      mutated gene known to date in sporadic breast cancer appears to be the tumor
      suppressor gene p53. This study was designed to determine the frequency of p53
      gene mutations in primary breast cancer, to correlate the presence of p53
      mutations with established clinicopathologic parameters, including the estrogen
      receptor (ER) and progesterone receptor (PR) status, and to assess the prognostic
      significance of p53 mutations regarding patient survival. METHODS: We examined
      the p53 gene in genomic DNA samples from 192 primary breast cancers. Using
      denaturant gradient gel electrophoresis, the authors analyzed exons 5-9 in all
      tumors for mutations and performed DNA sequencing in 20 tumors to identify the
      exact nature of the p53 mutations. RESULTS: p53 gene alterations were identified
      in 43 of the 192 tumors (22%), the majority localized in exons 5 and 6. DNA
      sequencing showed mostly missense mutations resulting from G or C substitutions.
      p53 mutations were found more often in tumors of younger women (P = 0.002), Afro
      American women (P = 0.05), and in tumors lacking ER (P = 0.03), PR (P = 0.04), or
      both (P = 0.06). There were no significant correlations with family history,
      tumor size, histologic grade or type, nodal status, or disease stage. The overall
      survival rates showed no significant difference between patients with mutant and
      wild-type p53 tumors. The same was true when the comparison was limited to node
      negative patients or patients with ER-positive or ER-negative tumors. Finally,
      there was no significant difference in survival between patients with tumors
      harboring mutations in exons 5 and 6 versus exons 7-9. CONCLUSIONS: The results
      of this and other studies demonstrate a consistent relationship between ER
      positive tumors and wild-type p53 on one hand and ER-negative cancers and p53
      mutations on the other. Our data do not support a significant prognostic role for
      p53 mutations in predicting survival.

PMID- 8156520
TI  - Factors predicting long-term survival for metastatic breast cancer patients
      treated with high-dose chemotherapy and bone marrow support.
AB  - BACKGROUND: Poor prognosis of Stage IV breast cancer patients have at best a 10%
      3-year survival rate with conventional chemotherapy. Dose-intensive chemotherapy
      improved survival rates for some of these patients. METHODS: All patients were
      Stage IV estrogen receptor-negative or estrogen receptor-positive hormonal
      refractory and received conventional chemotherapy (induction phase) to the point
      of achieving maximal response; if disease was stable or the patients responded,
      they entered high-dose chemotherapy (intensive phase). Seventy-six percent of the
      patients received two high-dose treatments with cyclophosphamide (4.5-6.0 g/m2),
      etoposide (750-1500 mg/m2), and cisplatin (120-180 mg/m2). Patients were
      randomized to receive or not receive autologous marrow. To identify prognostic
      factors for survival, univariate statistical analysis and multivariate models
      were applied to patient subsets. RESULTS: Univariate analysis identified a number
      of factors whose presence indicates improvement in overall survival rates. These
      include: (1) absence of liver relapse (P = 0.001); (2) absence of soft tissue
      relapse (P = 0.001); (3) a smaller number of metastatic sites at the time of
      detecting Stage IV disease (P = 0.026); and (4) disease-free interval greater
      than 1 year from initial diagnosis to Stage IV disease (P = 0.011). Multivariate
      models were fitted to the data, and three variables were identified as
      independent negative predictors for overall survival: (1) liver site (P = 0.001);
      (2) soft tissue site (P = 0.039); and (3) prior adjuvant chemotherapy (P =
      0.028). CONCLUSIONS: Shorter survival after high-dose chemotherapy is predicted
      independently by patients pretreated with adjuvant chemotherapy, by disease
      distributed to the liver or the soft tissue.

PMID- 8156521
TI  - Incidence and mortality from breast cancer in the Mama Program for Breast
      Screening in Finland, 1973-1986.
AB  - BACKGROUND: A cohort of women enrolled in the Mama breast self-examination-(BSE)
      containing breast screening program in Finland from 1973 through 1975 (with BSE
      used for screening and mammography for diagnosis) was studied. METHODS: Twenty
      eight thousand seven hundred eighty-five women who returned calendars recording
      their practice of BSE over a 2-year period have been followed by linkage with the
      records of the Finnish Cancer Registry through 1986. The incidence of and
      mortality from breast cancer was compared with that expected in the Finnish
      population based on a model incorporating Finnish national data for breast cancer
      incidence and case fatality. RESULTS: Breast cancer incidence was higher than
      expected (a rate ratio of 1.19 over all ages). The stage distribution of cases
      was not different from that expected from Finnish cancer registry data for 1980,
      but the breast cancer mortality was lower than expected (a rate ratio of 0.75).
      The latter difference occurred mainly in Years 3-6 of the follow-up period. The
      effect seemed similar in women under and over the age of 50 years. The cohort was
      of higher educational status than the Finnish population, and the mortality from
      all causes was lower than the general Finnish population, an effect seen in
      previous studies of compliers with breast screening. CONCLUSIONS: The reduction
      in mortality from breast cancer in the study cohort is consistent with an effect
      of the BSE-containing Mama program, though selection bias, inherent in any
      observational study of screening, provided an alternative explanation for the
      findings.

PMID- 8156522
TI  - Pregnancy and lactation after breast-conserving therapy for early stage breast
      cancer.
AB  - BACKGROUND: To identify patients treated with breast conservation therapy for
      early-stage breast cancer who subsequently experienced full-term pregnancies, and
      to identify: (1) The proportion of women who experienced lactation in the treated
      breast; and (2) treatment, disease, and/or host factors that may be related to
      the presence or absence of lactation and the ability to breast-feed successfully.
      METHODS: The records of 890 patients treated at the radiation therapy facilities
      of the Department of Therapeutic Radiology, Yale University, New Haven, CT, for
      early-stage (Stage I or II) breast cancer were reviewed to identify patients who
      had become pregnant subsequent to completing breast conservation therapy. Data
      were collected from the patients' departmental records, and interviews were
      conducted by phone and/or questionnaire. RESULTS: Thirteen patients were
      identified, and 11 patients who experienced 13 pregnancies were interviewed. All
      patients reported little or no swelling of the treated breast during pregnancy.
      After delivery, lactation from the treated breast was present in four instances,
      absent in six, and pharmacologically suppressed in three. One patient
      successfully breast-fed from the treated breast for 4 months. In the majority of
      cases, breast-feeding from the untreated breast was successful. The interval from
      the time of treatment to the time of delivery did not appear to affect adversely
      lactation from the treated breast; one patient reported lactation from the
      treated breast 75 months after completion of treatment. Circumareolar incision
      was associated with the absence of lactation in three patients (four
      pregnancies). Thus, lactation from the treated breast may be less likely to occur
      in the case of centrally located lesions. CONCLUSION: Successful breast-feeding
      from the untreated, as well as the treated breast, is possible after conservative
      surgery and radiation. Implications for patients of child-bearing age undergoing
      conservative surgery and radiation therapy are discussed.

PMID- 8156523
TI  - Intraductal carcinoma of the breast associated with high levels of circulating
      tumor-associated antigens (CA 15-3 and NCC-ST-439).
AB  - BACKGROUND: A remarkable elevation of serum tumor-associated antigen levels
      usually occurs in advanced or metastatic cancer and has not been reported
      previously in the setting of noninvasive carcinoma of the breast. METHODS: An
      immunohistochemical and histopathologic study is presented on a specimen taken
      from a 43-year-old Japanese woman with micropapillary intraductal carcinoma of
      the breast with significantly high levels of preoperative circulating tumor
      associated antigens, CA 15-3 (198.5 U/ml) and NCC-ST-439 (1400 U/ml). RESULTS: A
      histologic specimen consisted of numerous cysts lined by slightly stratified,
      monotonous columnar cells producing foci of micropapillary intraductal carcinoma.
      Extensive sampling of the specimen demonstrated no invasive foci although faintly
      eosinophilic secretory material occasionally leaked from disrupted cysts into the
      surrounding stroma. The cancerous and normal epithelium showed intense apical
      reactivity with monoclonal antibodies 115D8, DF3, and NCC-ST-439; intraluminal
      and spilled secretion also showed positive reaction with these antibodies. Serum
      levels of CA 15-3 and NCC-ST-439 were within normal limits after subcutaneous
      mastectomy. No carcinoembryonic antigen was demonstrated either in the sera, the
      neoplastic epithelium, or the secretory material. CONCLUSIONS: These
      histopathologic and immunohistochemical studies showed that the leaked secretion
      from the disrupted cysts into the surrounding connective tissue stroma may be
      responsible for the marked elevation of circulating tumor-associated antigen
      levels in this micropapillary intraductal carcinoma.

PMID- 8156524
TI  - Merkel's cell (neuroendocrine) carcinoma of the vulva.
AB  - BACKGROUND: Merkel's cell carcinoma rarely arises in the vulva. It is unclear
      whether those cases arising in the vulva behave differently from the usual
      Merkel's cell carcinomas. METHODS: A Merkel's cell carcinoma of the vulva was
      studied by light microscopy, immunohistochemistry, and electron microscopy. The
      clinical data of this case and of other reported cases are summarized and
      compared with those of Merkel's cell carcinoma in general. RESULTS: This tumor
      showed the characteristic trabecular pattern of Merkel's cell carcinoma. The
      tumor cells were immunoreactive to low-molecular-weight cytokeratin and neuron
      specific enolase. This patient was treated initially with local excision. She
      died 17 months later with progressive metastatic disease unresponsive to
      chemotherapy. This case study and the review of six other cases indicate that
      Merkel's cell carcinoma of the vulva is universally metastatic, both to the
      regional lymph nodes and distant sites, and that it invariably follows a rapidly
      fatal course. CONCLUSION: Merkel's cell carcinoma of the vulva appears to have a
      biologic behavior more aggressive than that of Merkel's cell carcinoma in
      general. An initial modality combining chemotherapy, with or without irradiation,
      with aggressive surgery should be tried in future cases.

PMID- 8156525
TI  - Contrasting trends of prostate cancer incidence and mortality in New Mexico's
      Hispanics, non-Hispanic whites, American Indians, and blacks.
AB  - BACKGROUND: Prostate cancer has increased in epidemic proportions during the
      1980s. Although marked differences in ethnic and racial temporal trends for
      prostate cancer have been observed both in the United States and internationally,
      the trends in Hispanics and American Indians have not been described extensively.
      METHODS: To characterize the occurrence of prostate cancer among non-Hispanic
      whites, Hispanics, American Indians, and blacks in New Mexico, the authors
      examined cancer incidence data collected by the New Mexico Tumor Registry for the
      period 1969-1991 and mortality data collected by the New Mexico Bureau of Vital
      Statistics for the period 1958-1991. RESULTS: From 1969 to 1991, age-adjusted
      incidence rates increased from 74.4 to 139.1 per 100,000 (87%) among non-Hispanic
      whites and from 54.0 to 94.7 (75%) among Hispanics. American Indians had the
      lowest incidence rates of all groups. Over the same period, incidence rates for
      local-stage cancers increased by 93% and 81% among non-Hispanic whites and
      Hispanics, respectively, but were stable for American Indians and blacks, whereas
      rates for regional-stage cancers increased sharply. Incidence rates of distant
      stage disease decreased among non-Hispanic whites from 1969 through 1991. In
      contrast, incidence rates of distant-stage disease among Hispanics increased
      through 1982. From 1983 to date, age-adjusted mortality rates of prostate cancer
      decreased among all groups except Hispanics. CONCLUSION: The patterns of
      incidence and mortality are consistent with a stage migration. The recent
      decrease in age-adjusted prostate cancer mortality rates for non-Hispanic whites
      is consistent with that expected following the decrease in distant-stage disease
      incidence. Differential access to medical care and prostate cancer screening may
      account for these trends.

PMID- 8156526
TI  - The significance of nucleolar organizer region (AgNOR) score in predicting
      meningioma recurrence.
AB  - BACKGROUND: Argyrophilic nucleolar organizer region (AgNOR) has been demonstrated
      in recent studies of human brain tumors, including meningiomas. The authors used
      this technique in meningiomas to analyze whether the mean numbers of AgNOR per
      nucleus (AgNOR score) are related to the recurrence rate or the proliferative
      potential of meningiomas. METHODS: AgNOR staining technique was applied to
      paraffin-embedded sections of 60 meningiomas. Twenty of these specimens also were
      investigated immunohistochemically with monoclonal antibody (MoAb) against DNA
      polymerase alpha (Pol.alpha) and with MoAb Ki-67 to compare the AgNOR score with
      the proliferative potential. RESULTS: There was a statistically significant
      difference between the AgNOR score in nonrecurrent meningiomas (2.48 +/- 0.73)
      and recurrent histologically benign meningiomas after gross total resection (3.20
      +/- 0.96) (P < 0.02). The recurrence rate of tumors after gross total resection
      with an AgNOR score of 3.0 or more was significantly higher than that with an
      AgNOR score of less than 3.0. The AgNOR score did not always correlate with
      Pol.alpha or Ki-67 score; the AgNOR score of malignant meningioma that had high
      proliferative score was not always high. CONCLUSIONS: This study indicates that
      AgNOR staining appears to be a simple and useful method for estimating the
      probability of histologically benign meningioma recurrence even after gross total
      resection.

PMID- 8156527
TI  - Description of a human papillary thyroid carcinoma cell line. Morphologic study
      and expression of tumoral markers.
AB  - BACKGROUND: The establishment of cell lines from thyroid carcinomas can provide
      an in vitro model of oncogenesis. B-CPAP is a new cell line that has been
      obtained from a differentiated papillary thyroid carcinoma. The data presented
      give a broader characterization and expression of tumoral markers of this cell
      line and identify the differentiated functions that are preserved. METHODS: An
      ultrastructural study was performed to confirm the thyroid nature of the new cell
      line. The cellular markers (thyroglobulin, S100, neuron-specific enolase [NSE])
      and the oncogenes (mutated p53, H-ras, c-myc, PTC, trk) were studied by
      immunohistochemistry, Southern blot, or in situ hybridization. RESULTS: The cells
      were of a differentiated ultrastructural thyroid type. All of the cells proved
      immunoreactive with antibodies specific to thyroglobulin, S100 proteins, NSE, and
      mutant p53 protein. Mutations of H-ras, PTC, and trk were not observed. The c-myc
      gene was not amplified. CONCLUSIONS: The cell line described in these data
      provides a suitable model for the study of thyroid carcinogenesis, given that the
      cells present thyroid characteristics, and metabolic disorders not previously
      found in such cell lines. In addition, the coexpression of S100 proteins and
      mutant p53 proteins in the cells should permit the study of the interaction
      between these two proteins.

PMID- 8156528
TI  - Adult Hodgkin's disease in Kerala.
AB  - BACKGROUND: Hodgkin's disease seen in the developing countries differs from that
      seen in developed countries. There are only a few reports from India regarding
      the epidemiologic and clinicopathologic features of Hodgkin's disease. METHODS:
      The records of 159 evaluable patients with Hodgkin's disease seen at the Regional
      Cancer Centre, Trivandrum, India, during the period 1983-1989 were reviewed for
      clinicoepidemiologic profile and survival analysis. The Kaplan-Meier product
      limit method was used to compute survival, and Cox proportional hazard regression
      analysis was used to study the factors affecting survival. RESULTS: The male-to
      female ratio was 3.1:1. The mean age at presentation was 38 years in adults.
      Supradiaphragmatic presentation (44.7%) was more common, and mixed cellularity
      (50.3%) was the predominant histologic subtype. There were 9.4% patients with
      Stage I disease, 37.1% with Stage II, 33.4% with Stage III, and 20.1% with Stage
      IV disease. Of the patients, 57.9% were treated with chemotherapy, whereas 23.3%
      had radiation therapy alone, and 18.8% had a combination of radiation therapy and
      chemotherapy. Complete response was noted in 77.4% (n = 123) of patients, of whom
      20.3% (n = 25) later experienced disease relapse. Second remission could be
      achieved in 8 of 25 patients with disease relapse. The overall 5-year survival
      rate was 55%. The stage-related survival rates were 89%, 69%, 53%, and 27% in
      Stage I-IV, respectively. On multivariate regression analysis, patient age and
      disease stage emerged as significant predictors of survival. CONCLUSION: Mixed
      cellularity was the most common histologic subtype. The inferior survival rate
      observed could be attributable to advanced stage of presentation, compromise on
      the drug and dose, and the lack of proper supportive measures. Patient age and
      disease stage were the important predictors of survival.

PMID- 8156529
TI  - Hypersensitivity reactions to carboplatin. Report of two patients, review of the
      literature, and discussion of diagnostic procedures and management.
AB  - BACKGROUND: Hypersensitivity reactions are rare but sometimes life-threatening
      complications of cytostatic combinations containing platinum compounds. Only
      approximately 40 instances of such hypersensitivity have been reported in
      association with carboplatin treatment. However, the symptoms probably often are
      misinterpreted. METHOD: Signs and symptoms of two patients with severe
      hypersensitivity reactions to carboplatin are presented. Intracutaneous tests
      with carboplatin were performed in these two patients and in five control
      patients receiving carboplatin therapy without unexpected side effects. RESULTS:
      Both patients had received several cycles of a carboplatin-containing combination
      chemotherapy. In both patients, hypersensitivity reactions became manifest for
      the first time after cumulative doses of 3900 and 5400 mg, respectively. Symptoms
      included dyspnea, tachycardia, angina pectoris, hypotension, diarrhea, edema, and
      rash. In both patients, a positive urticarial reaction to intracutaneous
      carboplatin (diluted 1:10 with normal saline) was observed, whereas five control
      patients undergoing carboplatin therapy without adverse reaction had negative
      test results. There were no signs of delayed hypersensitivity. Serum
      immunoglobulin E levels were normal. Symptoms were ameliorated but not suppressed
      when one patient was reexposed after premedication with corticosteroids and
      histamine antagonists. Both patients tolerated high doses of cisplatin without
      allergic reactions. CONCLUSIONS: Although they are rare, hypersensitivity
      reactions can be serious complications of carboplatin therapy. Simple
      intracutaneous tests might help to establish the diagnosis to avoid dangerous
      reexposures. Although the pathogenetic mechanisms are not fully understood, the
      clinical and experimental findings suggest an anaphylactic type of
      hypersensitivity, perhaps aggravated to some extent by nonspecific histamine
      liberation. There seems to be no general cross-reactivity to cisplatin.

PMID- 8156530
TI  - Significance of plasma PTH-rp in patients with hypercalcemia of malignancy
      treated with bisphosphonate.
AB  - BACKGROUND: Hypercalcemia of malignancy (HM) is one of the commonest metabolic
      complications associated with cancer. Plasma parathyroid hormone-related peptide
      (PTH-rp) is known to cause hypercalcemia in the vast majority of patients with
      HM. METHODS: Fifty-two patients with HM were treated with a single infusion of 60
      mg of pamidronate (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). Serum
      calcium and plasma PTH-rp levels were measured at the basal and after pamidronate
      therapy. RESULTS: Normocalcemia was achieved in 43 (i.e., 83%) of these patients
      within 3 to 5 days. Eighty-one percent had increased plasma PTH-rp levels. There
      was no difference in the percentages of patients who had elevated plasma PTH-rp
      levels compared with those of patients with metastatic bone disease and humoral
      HM. However, the latter group of patients had significantly higher circulatory
      PTH-rp levels (P < 0.01). The pretreatment calcium levels were not correlated
      with the calcium-lowering responses nor with plasma PTH-rp levels. However, there
      was a significant positive correlation between pretreatment plasma PTH-rp levels
      and the nadir serum calcium (P < 0.001) and a negative correlation with the
      changes in serum calcium levels (P < 0.001) after pamidronate therapy. No
      relationship existed between pretreatment calcium levels or PTH-rp levels with
      the extent or the severity of the metastatic bone disease. Patients who had the
      highest PTH-rp levels had the worst prognosis, poorest calcium-lowering effect,
      shortest duration of normocalcemia, and required higher doses and frequent
      infusions of pamidronate to maintain normocalcemia. The nonresponders to therapy
      had a significantly higher mean plasma PTH-rp level (> 75 pg/ml) than the
      responders (P < 0.01). CONCLUSIONS: The plasma PTH-rp levels may help to predict
      the calcium-lowering effect of bisphosphonate and give an indication of the
      prognosis in patients with HM. They may allow identification of patients who need
      higher doses and increased frequency of administration of bisphosphonate, thereby
      expediting the normocalcemic response.

PMID- 8156531
TI  - MYCN gene amplification in rhabdomyosarcoma.
AB  - BACKGROUND: Amplification of the MYCN oncogene, formerly known as N-myc, has been
      seen in several malignant tumors, particularly neuroblastoma, where its
      association with a poor clinical outcome is the clearest example of a clinically
      relevant oncogene mutation in any human cancer. METHODS: The incidence and
      clinical significance of MYCN amplification in rhabdomyosarcoma (RMS) was
      assessed by Southern blot analysis in this retrospective study of seven alveolar
      RMS and six embryonal RMS. RESULTS: MYCN amplification (4- to 13-fold) was
      present in three of seven alveolar RMS (42.9%) but in none of the embryonal RMS.
      There was no significant difference between the clinical behavior of the MYCN
      amplified and unamplified tumors, and no correlation was found with the light
      microscopic appearances of the tumors or with desmin immunoreactivity.
      CONCLUSIONS: The findings are compatible with previous studies that demonstrated
      cytogenetic evidence of gene amplification in RMS, and help to clarify
      conflicting reports in the literature about MYCN amplification in alveolar and
      embryonal RMS. The results raise the possibility of important biologic
      differences between these subtypes of RMS, differences that warrant further
      investigation.

PMID- 8156532
TI  - Multimedia in the radiology environment: current concept.
AB  - Multimedia has different meanings according to its context. Here, multimedia in
      the radiology environment is defined as the integration of multiple radiology and
      medical information systems to facilitate the practice of radiology. These
      information systems include the hospital information system, radiology
      information system, picture archiving and communication systems, voice reporting,
      library information systems, and electronic mail and file systems. The concept of
      multimedia within the context of integration of these database systems will be
      presented. An example is given on how to access these information systems by a
      radiologist's desktop personal computer.

PMID- 8156533
TI  - Automatic detection of intracranial contours in MR images.
AB  - Segmentation of the intracranial cavity in medical images is valuable in several
      research areas such as the quantitative analysis of normal and abnormal brain
      tissues, the registration of different imaging modalities (MRI, PET, CT) based on
      surface models of the brain, and the rendering of volume data. Because the manual
      delineation of the brain contour in the images can be demanding and error prone,
      an automatic procedure to perform this task is desirable. We have developed and
      tested a robust method that permits the automatic detection of the intracranial
      contour in transverse MR images. The method is described and its performance
      evaluated.

PMID- 8156534
TI  - Estimation of CSF, white and gray matter volumes in hydrocephalic children using
      fuzzy clustering of MR images.
AB  - An algorithm and set of procedures for measuring volumes of cerebrospinal fluid
      (CSF), white matter, and gray matter from transaxial magnetic resonance images
      (MRI) of the brain are described. The algorithm is a variant of the fuzzy c-means
      clustering method for texture identification. This technique is used mainly to
      solve the problem of volume averaging of tissue compartments, but also has other
      advantages. It is fast, accurate, and relatively operator independent.
      Furthermore, it does not depend on statistical assumptions such as data
      normality, nor does it require any a priori heuristics. The procedure was tested
      successfully on imaged phantoms of known volume composition and compared with
      results achieved using a standard morphometric measurement approach. The
      procedure was also applied to brain MRIs of three clinically normal children and
      three age-matched children with hydrocephalus using both proton density and T2
      weighted images. The algorithm was able to detect the expected increased amounts
      of CSF and decreased amounts of white matter characteristic of the hydrocephalic
      brain.

PMID- 8156535
TI  - Duplex-Doppler spectral analysis in the physiopathology of the temporomandibular
      joint.
AB  - We introduce a new method of analysis of the normal and abnormal behavior of the
      TMJ, using a duplex-doppler spectral analysis. The method consists in monitoring
      the joint movement by means of a study of the Fourier transformed signals, which
      give information on the velocity distribution of the condylo-meniscal complex
      during the opening and closing phases of the jaw. Using repeated sampling over
      short time intervals we get a detailed description of the motion which allows to
      discriminate the normal and abnormal action of the condylomeniscal complex. We
      are able to identify various physiopathological conditions, among which opening
      and/or closing clicks, complex locking conditions and anomalies related to an
      asymmetrical behavior during the operation cycle. Duplex-doppler spectral
      analysis is correlated to a clinical examination in order to define various
      classes of anomalies.

PMID- 8156536
TI  - Magnetic resonance imaging of patients with intention tremor.
AB  - We evaluated the magnetic resonance images of the patients with intention tremor.
      Five patients out of seven had some atrophic structures or changes in signal
      intensity in the cerebello-rubral thalamic tract. Moreover, the T2-weighted
      images of the patients group detected the dentate and red nuclei more poorly than
      those of our control group. From these results, the etiological significance of
      the tract was confirmed and the mechanism of the intention tremor onset was
      discussed.

PMID- 8156537
TI  - Progressive Bochdalek hernia with unusual ureteral herniation.
AB  - An asymptomatic case of a Bochdalek hernia with progressive herniation of the
      right ureter is presented. The diagnosis was made by computed tomography (CT).

PMID- 8156538
TI  - Unknown primary tumours.

PMID- 8156539
TI  - Treatment of acquired immunodeficiency syndrome (AIDS)-related cancer.

PMID- 8156540
TI  - Adoptive cellular therapy of urological neoplastic disease.

PMID- 8156541
TI  - Neurotoxicity secondary to antineoplastic drugs.

PMID- 8156542
TI  - The structure and (local) stability constants of borate esters of mono- and di
      saccharides as studied by 11B and 13C NMR spectroscopy.
AB  - The formation of borate esters of various mono- and di-saccharides in aqueous
      solution was studied by 11B and 13C NMR spectroscopy. Association constants K(B
      L) at a carbohydrate-borate molar ratio of 1:1, pH 7, and 25 degrees C were
      determined and compared with literature values obtained from potentiometry. The
      association constants K(B-L) were converted into local association constants
      Kloc(B-L) by using the distribution of the various anomeric forms in D2O. In this
      way, values of Kloc(B-L) were obtained, which appear to be characteristic of the
      configuration concerned. They explain the favourable effect of borate in the
      alkaline isomerisation of lactose into lactulose. At a low molar ratio (1:3) of
      carbohydrate-borate, predominantly diborate esters (B-)2L were formed.

PMID- 8156543
TI  - Chemical synthesis of the pyruvic acetal-containing trisaccharide unit of the
      species-specific glycopeptidolipid from Mycobacterium avium serovariant 8.
AB  - The functionalized, pyruvic acetal-containing haptenic trisaccharide, p
      trifluoroacetamidophenyl 6-deoxy-2-O-(3-O-[4,6-O-(S)-(1
      methoxycarbonylethylidene)-3-O-meth yl- beta-D-glucopyranosyl]-alpha-L
      rhamnopyranosyl)-alpha-L-talopyranosid e (19), a component of the glycolipid from
      Mycobacterium avium serovar 8 was synthesized. For the preparation of the
      terminal pyruvic acetal-containing unit, benzyl 2-O-benzyl-3-O-methyl-beta-D
      glucopyranoside (6) was condensed with methyl 2,2-di(ethylthio)propionate (1) in
      the presence of SO2Cl2-CF3SO3H catalyst to yield benzyl 2-O-benzyl-4,6-O-(S)-(1
      methoxycarbonylethylidene)-3-O-methyl-beta -D- glucopyranoside (7S), which was
      then converted into the suitably substituted glycosyl donor 2-O-acetyl-4,6-O-(S)
      (1-methoxycarbonylethylidene)-3-O-methyl-alph a-D- glucopyranosyl
      trichloroacetimidate (11). The disaccharide glycosyl acceptor p-nitrophenyl endo
      3,4-O-benzylidene-6-deoxy-2-O-(2,4-di-O-benzyl-alpha-L-rhamnopyrano syl)- alpha-L
      talopyranoside (15) was glycosylated with 11 in the presence of trimethyl
      trifluoromethanesulfonate to furnish the protected trisaccharide p-nitrophenyl 2
      O-(3-O-[2-O-acetyl-4,6-O-(S)-(1-methoxycarbonylethylidene)-3-O-m ethyl-beta- D
      glucopyranosyl]-2,4-di-O-benzyl-alpha-L-rhamnopyranosyl)-endo-3,4- O-benzylidene
      6-deoxy-alpha-L-talopyranoside (16). After deprotection, this gave the spacer
      armed unprotected haptenic trisaccharide 19.

PMID- 8156544
TI  - Synthesis of three tetrasaccharides containing 3-O-methyl-D-mannose, as model
      compounds for xylose-containing carbohydrate chains from N-glycoproteins.
AB  - The synthesis is reported of methyl 3,6-di-O-(3-O-methyl-alpha-D-mannopyranosyl)
      2-O-beta-D-xylopyranosyl-be ta-D- mannopyranoside (2), methyl 6-O-alpha-D
      mannopyranosyl-3-O-(3-O-methyl-alpha-D-mannopyranosyl)-2-O-b eta-D- xylopyranosyl
      beta-D-mannopyranoside (3), and methyl 3-O-alpha-D-mannopyranosyl-6-O-(3-O-methyl
      alpha-D-mannopyranosyl)-2-O-b eta-D- xylopyranosyl-beta-D-mannopyranoside (4).
      The various methyl beta-D-Manp acceptor derivatives were prepared from the
      corresponding methyl beta-D-Glcp derivatives via oxidation-reduction. All
      glycosyl donors were coupled using the trichloroacetimidate method at -40 degrees
      C in dichloromethane with trimethylsilyl triflate as a catalyst. Methyl-3-O
      benzyl-4,6-O-benzylidene-beta-D-mannopyranoside (7) was condensed with 2,3,4-tri
      O-acetyl-alpha-D-xylopyranosyl trichloroacetimidate (8). Regioselective reductive
      4,6-O-benzylidene ring-opening on the resulting disaccharide derivative, followed
      by acetylation, and hydrogenation gave methyl 4-O-acetyl-2-O-(2,3,4-tri-O-acetyl
      beta-D-xylopyranosyl)-beta-D-mannopyr anoside (12). Coupling of 12 with 2,4,6-tri
      O-acetyl-3-O-methyl-alpha-D-mannopyranosyl trichloroacetimidate (18) afforded
      tetrasaccharide derivative 19, and subsequent O-deacetylation gave 2. Methyl 3-O
      benzyl-4,6-O-prop-2-enylidene-beta-D-mannopyranoside (22) was condensed with
      2,3,4-tri-O-acetyl-alpha-D-xylopyranosyl trichloroacetimidate (8). Regioselective
      reductive 4,6-O-prop-2-enylidene ring-opening on the resulting disaccharide
      derivative, followed by acetylation, and deallylation at O-6 gave methyl 4-O
      acetyl-3-O-benzyl-2-O-(2,3,4-tri-O-acetyl-beta-D-xylopyranosyl)-beta -D-
      mannopyranoside (26-a), which was either condensed with 2,3,4,6-tetra-O-acetyl
      alpha-D-mannopyranosyl trichloroacetimidate (27) or 18, to give trisaccharide
      derivatives 28 or 31, respectively. Debenzylation of 28 followed by condensation
      with 18 gave, after O-deacetylation, 3, whereas debenzylation of 31 followed by
      condensation with 27 gave, after O-deacetylation, 4.

PMID- 8156545
TI  - Synthesis of 5-aminopentyl mono- to tri-saccharide haptens related to the species
      specific glycopeptidolipids of Mycobacterium avium-intracellulare serovars 8 and
      21.
AB  - The preparation of pyruvate acetal-containing 5-aminopentyl mono-, di-, and tri
      saccharide fragments related to serovars 8 and 21 of the species-specific
      glycopeptidolipid of Mycobacterium avium-intracellulare is described. The
      saccharides were constructed by sequential coupling of the suitably protected 4,6
      O-[(S)-1-methoxycarbonylethylidene]-D-glucopyranosyl trichloroacetimidates 6 and
      7 to Z-protected 5-aminopentanol, to give the serovar 21 monosaccharide fragment
      9 upon deblocking; and to ethyl 2-O-benzoyl-4-O-benzyl-1-thio-alpha-L
      rhamnopyranoside (18), to give the corresponding ethyl 1-thio-disaccharides 21
      and 23, respectively. Subsequent N-iodosuccinimide-promoted coupling of the
      latter with Z-protected 5-aminopentanol followed by deblocking of the products
      afforded the corresponding disaccharide fragments 26 (serovar 8) and 27 (serovar
      21), respectively. Condensation of 21 with Z-protected 5-aminopentyl 3,4-di-O
      benzyl-6-deoxy-alpha-L-talopyranoside (28) and subsequent deblocking of the
      resulting trisaccharide gave the serovar 8 fragment 5-aminopentyl O-(4,6-O-[(S)-1
      carboxyethylidene]-3-O-methyl-beta-D-glucopyranosyl)- (1-->3)-O-alpha-L
      rhamnopyranosyl-(1-->2)-6-deoxy-alpha-L-talopyranos ide (30).

PMID- 8156546
TI  - Synthesis of 5-aminopentyl 4,6-O-[(R)-1-carboxyethylidene]-beta-D
      galactopyranoside and its use as a ligand for the affinity chromatography of
      human serum amyloid P . protein.
AB  - A series of 2,3-di-O-benzoyl-D-galactopyranosides, alpha-allyl (5), alpha-benzyl
      (6), beta-ethyl-1-thio (7), beta-phenyl-1-thio (8), and alpha-methyl (9),were
      prepared from the corresponding 4,6-O-benzylidene derivatives and were acetalated
      in acetonitrile with methyl pyruvate, to give diastereoselectively the 2,3-di-O
      benzoyl-4,6-O-[(R)-1-methoxycarbonylethylidene]-D- galactopyranosides 10-16. The
      latter were converted into the 2,3-di-O-benzoyl-4,6-O-[(R)-1
      methoxycarbonylethylidene]-D-galacto pyranosyl alpha- and beta
      trichloroacetimidates 19 and 20, alpha- and beta-fluorides 21 and 22, the alpha
      bromide 23, and the alpha-chloride 24, respectively. These donors, including the
      phenyl 1-thiogalactoside 14, reacted with 5-[(benzyl-oxycarbonyl)amino]pentanol
      to give the corresponding protected beta-D-galactoside 27, deblocking of which
      afforded the title compound 1. Binding of 1 to epoxypropyl-modified acrylamide
      beads gave an affinity adsorbent that was used to isolate serum amyloid P protein
      from human serum.

PMID- 8156547
TI  - A convenient synthesis for anomeric 2-thioglucobioses, 2-thiokojibiose and 2
      thiosophorose.
AB  - 2-S-alpha-D-Glucopyranosyl-2-thio-D-glucopyranose (2-thiokojibiose, 8) and 2-S
      beta-D-glucopyranosyl-2-thio-D-glucopyranose (2-thiosophorose, 14) were
      conveniently prepared by SN2 reaction of the corresponding anomers of 2,3,4,6
      tetra-O-acetyl-1-thio-D-glucopyranose with 1,3,4,6-tetra-O-acetyl-2-O-tri-flyl
      beta-D-mannopyranose, followed by a deprotection sequence for the anomeric
      acetate involving conversion into the 1-propenyl glycosides. Alkaline O
      deacetylation was followed by smooth hydrolysis of the propenyl group at pH
      approximately 2.

PMID- 8156548
TI  - A synthetic route to 3-C-alkyl (or 3-C-phenyl-) 2,3-dideoxy-D-erythro-pentono-1,4
      lactones: intermediates in the synthesis of 2(3H)-furanones.
AB  - A series of 3-C-alkyl- (and 3-C-phenyl-) 2,3-dideoxy-D-erythro-pentono-1,4
      lactones, compounds which are important in the synthesis of modified nucleosides
      and antibiotic sugars, were synthesized from D-ribonolactone. By a route that
      proceeded via 5-O-protected D-ribonolactone, 5-O-protected 2,3-dideoxy-D-glycero
      pent-2-enono-1,4-lactones were synthesized and reacted with R2CuLi or a complex
      PhSCu(RMgBr)n to give respectively the 3-C-alkyl or 3-C-phenyl compounds. Details
      of the preparation of the O-protected intermediates, as well as the selection of
      the organometallic reagents, are provided.

PMID- 8156549
TI  - Synthesis of some 2-C-alkyl-2,3-dideoxy-alpha,beta-L-glycero-tetrurono-1,4
      lactones . Evaluation as antitumor agents.
AB  - A series of 3-C-alkyl-2,3-dideoxy-5-O-trityl-D-erythro-pentono-1,4-lactones were
      detritylated. The resultant free-hydroxy compounds were converted to their
      respective 2-C-alkyl-2,3-dideoxy-alpha,beta-L-glycero-tetrurono-1,4-lactones (L
      sugar numbering) in a one-vessel reaction sequence of (a) conversion of the
      lactones to their aldonic acid sodium salts, (b) cleavage of the resulting
      aldonates with sodium metaperiodate, and (c) acidification, followed by
      acetylation, to give the title compounds. The unsubstituted tetrurono-1,4
      lactones were inhibitory toward L1210 leukemia cells at concentrations in the 10(
      4) M range.

PMID- 8156550
TI  - Sugars with nitrogen in the ring isolated from the leaves of Morus bombycis.
AB  - It is known that 1-deoxynojirimycin (1) is contained in the leaves and roots of
      Morus sp. The modified purification procedures of 1 from leaves of Morus bombycis
      led to the isolation of many polyhydroxylated alkaloids. These include 1, N
      methyl-1-deoxynojirimycin (2), 2-O-alpha-D-galactopyranosyl-1-deoxynojirimycin
      (3), fagomine (4), 1,4-dideoxy-1,4-imino-D-arabinitol (5), 1,4-dideoxy-1,4-imino
      (2-O-beta-D-glucopyranosyl)-D-arabinitol (6), and 1 alpha,2 beta,3 alpha,4 beta
      tetrahydroxy-nor-tropane (7), designated nortropanoline. The isolation of 2 is
      the first report of its natural occurrence. Compounds 3 and 6 are the first
      naturally occurring glycosides of 1 and 5, respectively. Natural alkaloidal
      glycosidase inhibitors are classified into five structural types: namely
      polyhydroxylated piperidines, pyrrolidines, pyrrolines, indolizidines, and
      pyrrolizidines. Nortropanoline is a novel tropane alkaloid and a new type of
      polyhydroxylated alkaloid.

PMID- 8156551
TI  - Structural elucidation of the capsular polysaccharide expressed by Escherichia
      coli O20:K83:H26 by high resolution NMR spectroscopy.
AB  - The structure of the capsular polysaccharide produced by Escherichia coli
      O20:K83:H26 was investigated by one- and two-dimensional 1H and 13C NMR
      spectroscopy, and by glycose and methylation analysis. The capsular
      polysaccharide was shown to be comprised of linear pentasaccharide repeating
      units with the structure: [formula: see text]

PMID- 8156552
TI  - The structure of the polysaccharide produced by Proteus vulgaris (ATCC 49990).
AB  - An exocellular polysaccharide produced by a clinical isolate of Proteus vulgaris
      (ATCC 49990) was shown by composition, methylation, periodate oxidation, and
      nuclear magnetic resonance analyses to be composed of repeating trisaccharide
      units containing D-galactose, 2-acetamido-2-deoxy-D-glucose and pyruvic acid
      (2:1:1), and having the structure: [formula: see text] The homologus smooth
      lipopolysaccharide of the P. vulgaris strain was determined to have an O
      polysaccharide component having the same structure as the above extracellular
      polysaccharide.

PMID- 8156553
TI  - A Phanerochaete chrysosporium beta-D-glucosidase/beta-D-xylosidase with
      specificity for (1-->3)-beta-D-glucan linkages.
AB  - Phanerochaete chrysosporium is the best studied organism with respect to lignin
      degradation, but its degradation of the xylan component of lignocellulose is only
      now being studied. When grown on oat spelt xylan (mainly arabinoxylan), it
      produces an enzyme with beta-D-xylosidase and beta-D-glucosidase activity. This
      enzyme was purified by ultrafiltration followed by ammonium sulphate
      precipitation, anion-exchange chromatography using DEAE Biogel and Mono Q, and
      gel filtration using Superose 12. It is extracellular, with an apparent M(r)
      value of 44,500 as determined by SDS-PAGE; the pI is 4.67 and activity is maximal
      at pH 5 and 60 degrees C. The enzyme is of particular interest because its
      principal activity is against laminaribiose (3-O-beta-D-glucopyranosyl-D
      glucopyranose and laminarin [(1-->3)-beta-D-glucan with ca. 3% of beta-(1-->6)
      branches] rather than cellobiose and xylobiose. It was competitively inhibited by
      D-glucono-1,5-lactone and deoxynojirimycin; with p-nitrophenyl beta-D
      xylopyranoside as substrate, the Ki values were 32 and 87.5 microM, respectively,
      and with p-nitrophenyl beta-D-glucopyranoside, they were 35 and 68.7 microM,
      respectively. The Km values with p-nitrophenyl beta-D-xylopyranoside and p
      nitrophenyl beta-D-glucopyranoside as substrates were 3.51 and 5.30 mM,
      respectively.

PMID- 8156554
TI  - Synthesis of a tetrasaccharide related to the repeating unit of the antigen from
      Klebsiella type 55.

PMID- 8156555
TI  - Structure of the polysaccharide S-156 elaborated by Klebsiella pneumoniae ATCC
      316 46.

PMID- 8156556
TI  - Structure of the capsular K96 polysaccharide (K96 antigen) from Escherichia coli
      O77:K96:H- and comparison with the capsular K54 polysaccharide (K54 antigen) from
      Escherichia coli O6:K54:H10.

PMID- 8156557
TI  - Bemisiose: an unusual trisaccharide in Bemisia honeydew.

PMID- 8156558
TI  - Conformational equilibria of 4-thiomaltose and nitrogen analogues of maltose in
      aqueous solutions.
AB  - The 1H and 13C NMR data at neutral pH are presented for methyl 4-thio-beta- and
      alpha-maltoside (1 and 2) together with methyl 1-thio-alpha-D-glucopyranoside (3)
      and methyl 4-thio-alpha-D-glucopyranoside (4) as reference compounds.
      Furthermore, the NMR data at high and low pH are presented for the 4-amino-4
      deoxy analogues of methyl alpha-maltoside (5 and 6) and the 5-amino-5-deoxy
      analogue (8) together with reference compounds methyl 4-amino-4-deoxy-alpha-D
      glucopyranoside (7) and 1-deoxynojirimycin (9). The experimental NMR data are
      assigned by 1- and 2-dimensional spectroscopy at 500 and 600 MHz. The
      conformational preferences of the maltose analogues 1, 2, 5, 6 and 8 are
      evaluated by difference NOE experiments, 13C-1H long-range coupling constants,
      chemical-shift comparison with model compounds and hard-sphere force field
      calculations for 1 using Monte Carlo simulations. Additionally, the results are
      compared with extensive experimental NOE data for methyl alpha- and beta
      maltoside and the results discussed in light of earlier studies.

PMID- 8156559
TI  - NMR spectroscopic investigation of agarose oligomers produced by an alpha
      agarase.
AB  - The 13C NMR signals of various even and odd agarose oligosaccharides with either
      D-galactose or 3,6-anhydro-alpha-L-galactose at the reducing end have been
      assigned. The chemical shifts in water of the agaro- and the neoagaro
      oligosaccharides are compared and the influence of dimethyl sulfoxide on the
      chemical structure of the agaro-oligosaccharides is reported. The 3,6-anhydro-L
      galactose residue at the reducing end of agaro-oligosaccharides is in the
      hydrated form.

PMID- 8156560
TI  - [Synthesis of 6-O-beta-D-apiofuranosyl-beta-D-glucopyranosides of monoterpenyls].
AB  - The synthetic apiosyl-glucosides having (S)-3,7-dimethyl-1,6-octadien-3-yl
      (linalyl); (R)-1-methyl-1-(4-methyl-3-cyclohexen-1-yl)ethyl (terpineyl); (E) and
      (Z)-3,7-dimethyl-2,6-octadien-1-yl (geranyl and neryl); (S)-3,7-dimethyl-6-octen
      1-yl (citronellyl); benzyl and 2-phenylethyl as aglycon moiety were prepared
      using the stereospecific trichloroacetimidate Schmidt method. The key
      intermediate diholoside 1,2,3,4-tetra-O-acetyl-6-O-[(3-C-acetoxymethyl)-2,3-di-O
      acetyl-beta-D- erythrofuranosyl)-beta-D-glucopyranose was obtained by Kochetkov
      glycosylation of a branched-chain tetrofuranose cyanoethylidene derivative. The
      NMR data (1H and 13C) of the synthetic compounds and the glycosylation shifts of
      the apiose moiety are reported.

PMID- 8156561
TI  - Approximal plaque pH following topical applications of standard buffers in vivo.
AB  - In this study, the null hypothesis was tested that topical application of
      standard buffer solutions, pH 7.00 and pH 4.01, to 4-day-old plaque deposits
      accumulated in situ causes the plaque to attain the pH values of the buffer
      solutions applied. Following a 4-day abstention from all oral hygiene procedures,
      the plaque pH of four interdental sites in each of 5 volunteers was measured at
      resting state and following topical applications of buffers pH 7 and pH 4. Later
      the same day plaque pH was measured following rinses with the buffers. Topical
      application of buffer pH 7 caused a plaque pH increased from a mean value of 6.40
      to 6.59 within 30 s, while buffer pH 4 caused plaque pH to drop to a mean value
      of 5.11. Rinsing with buffers caused plaque pH to increase to 6.50 (buffer pH 7)
      and to drop to 4.92 (buffer pH 4). Statistical analysis of the results led to
      rejection of the null hypothesis. The results thus indicated that the validity of
      the in situ approach of calibration of plaque-covered indwelling electrodes may
      be questioned.

PMID- 8156562
TI  - Interexaminer agreement for readings of dip slide tests for salivary mutans
      streptococci and lactobacilli.
AB  - This study reports the interexaminer agreement of three pairs of evaluators of
      salivary dip slide tests for mutans streptococci and lactobacilli. 717
      Cariescreen SM and Bactotest LB dip slides were available for assessment by 2
      dentists and 1 dental hygienist. A single calibration session was held prior to
      the onset of the study. Each dip slide was read once by each examiner
      independently. Among the three pairs of examiners, Pearson R values ranged from
      0.84 to 0.90 for Cariescreen and from 0.78 to 0.87 for Bactotest. Kappa statistic
      values ranged from 0.56 to 0.61 for Cariescreen and from 0.70 to 0.74 for
      Bactotest. The range of agreement was from 72.2 to 76.9% for Cariescreen and from
      86.4 to 88.3% for Bactotest. The majority of disagreements were of one category
      in magnitude, though there were a few disagreements of greater magnitude. This
      study found moderately strong agreement among the three examiners; it suggests
      that multiple examiners of dip slide tests carefully calibrated initially and
      periodically to ensure a high level of agreement.

PMID- 8156563
TI  - Effect of various post-brushing activities on salivary fluoride concentration
      after toothbrushing with a sodium fluoride dentifrice.
AB  - The study consisted of eight experiments, divided into three series, aimed at
      investigating the effect on the salivary fluoride (F) concentration of three post
      brushing regimes: (1) rinsing once or twice with water, (2) rinsing either with a
      slurry of the toothpaste foam and water or with an 0.05% NaF solution, or a
      single NaF mouthrinse with no prior brushing, and (3) chewing and drinking
      ('eating') for 2 min. Brushing was done with 1.5 g of an 0.32% NaF dentifrice.
      The concentration of F in whole saliva was determined in 15 subjects at various
      time points up to 45 min after completing each experimental procedure. Results
      showed that the initial (0 min post-brushing) F concentration in saliva decreased
      about 1-2 times after a single, and 4-5 times after a double post-brushing water
      rinse, as compared with no rinsing at all (p < 0.001). Brushing followed by a
      mouthrinse with an 0.05% NaF solution elevated the F concentration more than
      brushing alone (p < 0.001). Rinsing with the slurry of toothpaste foam and water
      gave only a somewhat (but not significantly) lower concentration of F in saliva
      than just rinsing with the 0.05% NaF solution. Eating immediately after brushing
      reduced the salivary F level about 12-15 times (p < 0.001) compared with brushing
      alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156564
TI  - Influence of oral hygiene on early enamel caries.
AB  - For 548 children aged 4-16 years, mean (+/- SD) age 10.3 +/- 2.7 at visit 1, the
      dental status was recorded at four consecutive 6-monthly visits. Simultaneously
      oral hygiene was scored according to a modified patient hygiene performance (PHP)
      index after application of disclosing solution and before the dental examination.
      The following cariogenic changes could be observed: initiation (white spot
      formation), progression (cavitation), stabilisation and regression (disappearance
      of a white spot). The PHP score was examined in relation to these changes in
      smooth surfaces, as well as in fissures. For fissures when oral hygiene worsened,
      stabilisation of a white spot increased significantly. Also, regression of a
      white spot into sound enamel increased with poor oral hygiene, but the
      significance was only marginal. White spots turning into cavities, however, did
      not change with poor oral hygiene. It was speculated that under low oral hygiene
      conditions the remaining plaque of children receiving intensive fluoride
      treatment can bind fluoride to the fissure surfaces, thereby promoting enamel
      maturation concomitant with stabilisation and regression of white spots, which in
      an earlier study were also found to be dependent on posteruptive age.

PMID- 8156565
TI  - The application of molecular genetics to the microbiology of dental caries.
AB  - The introduction of techniques for the manipulation of DNA in vitro has had an
      enormous impact on progress in every area of biological research. In the case of
      oral microbiology, the first reports on the application of molecular genetics to
      streptococci started to appear in the early 1980s, and it is now more than 10
      years since the first paper describing cloning and expression of a gene from
      Streptococcus mutans in another bacterium was published. The purpose of this
      review is not to provide a resume of all the work that has been done on the
      molecular biology of oral bacteria; indeed, we are approaching the stage when a
      comprehensive survey of work on all oral bacteria is no longer feasible--for
      instance, over 40 genes have now been cloned and sequenced from S. mutans alone-
      but rather to illustrate examples of how the new techniques have been applied to
      give novel approaches and insights into old problems, or expand into new
      directions. The great majority of published work so far relates to streptococci,
      and many aspects have been covered in previous review articles [Curtiss, 1985;
      Russell, 1991], the most recent thorough review being that by Kuramitsu [1993].
      Discussion of molecular biology is now so all-pervasive that most readers will be
      familiar with many of the basic terms, but it may be worth clarifying some of the
      main points during the course of this article. For total novices, the short book
      by Brown [1990] forms a useful introduction. A number of recent articles have
      reviewed recent research on plaque formation [Kolenbrander and London, 1993] and
      the mutans streptococci in particular [Loesche, 1986], while Freedman et al.
      [1981] and Tanzer [1992] have summarised the information derived from a genetic
      approach to oral microbiology before the advent on in vitro manipulation of DNA.

PMID- 8156566
TI  - Fluoride profile in mature unerupted enamel following removal of surface organic
      material.
AB  - The aim of the present study was to determine fluoride profiles in mature
      unerupted enamel following removal of the surface organic material. Thirty teeth
      were randomly allocated into three groups. The surface organic material
      (Nasmyth's membrane) was left intact in group I; it was removed by tooth-brushing
      in group II, and in group III the surface organic layer was removed along with
      subsurface organic material by deproteinizing. Each tooth was then sectioned into
      halves and a standardized biopsy area was created. Initially alkali-soluble
      fluoride was extracted with 1M KOH followed by acid etch analysis to measure the
      remaining fluoride. No difference was seen in the alkali-soluble fluoride levels
      but residual fluoride concentrations were significantly reduced (p < 0.05) after
      deproteinizing but not after toothbrushing. It would appear that a substantial
      amount of fluoride (approximately 25%) in mature enamel from unerupted teeth can
      be removed by a deproteinizing agent, which may suggest an association of this
      fluoride with subsurface organic material.

PMID- 8156567
TI  - Secondary caries in dentine around composites: a wavelength-independent
      microradiographical study.
AB  - Composite restorations are prone to develop secondary caries if a gap exists
      between tissue and restoration. The aim of this article was to quantify the
      effects of a fluoridating and non-F composite on secondary dentine caries in
      vitro as a function of time. The mineral loss in dentine was assessed in an
      artificial gap of 200 microns width at the composite/dentine interface; the
      samples were demineralised in a carboxymethylcellulose gel (pH = 5, 37 degrees C)
      for 8 weeks. Once a week the mineral content of the samples was determined using
      non-destructive wavelength-independent microradiography (WIM). After 8 weeks
      transversal microradiography (TMR) was done on the samples to investigate the
      mineral distribution of the dentine lesions. The WIM results show that the
      fluoride-releasing composite decreased the dentine demineralisation statistically
      significantly with respect of the non-F control by approximately 45%. The mineral
      loss values are found to be strictly proportional to time; the demineralisation
      reduction is expected to continue over extended periods of clinical relevance.
      The TMR results show that the fluoridating composite reduced the mineral loss
      values significantly with respect to the non-F control by approximately 55%, but
      had a negligible effect on the lesion depth values. This study indicates that WIM
      is an accurate and reliable technique to measure in vitro secondary dentine
      caries next to a composite restoration as a function of time.

PMID- 8156568
TI  - Reduction in acid tolerance of Streptococcus downeii by fluoride and potassium
      laurate.
AB  - Streptococcus downeii MFe28 maintains a transmembrane pH gradient at low
      extracellular pH values using energy from glucose metabolism. The metabolic
      activity was measured in saturating glucose solutions using a pH-stat, and
      results were expressed as rates of titratable acid production at defined pH
      values. The tolerance to acid shock was studied in terms of the ability of cells
      to resume acid production at pH 8.0 following short-term exposure to low-pH
      environments. The results with control cells showed an optimum rate of acid
      production at pH 8.0. The activity extended to pH 4.5 with a half-maximal rate at
      pH 5.4. Addition of carbonyl cyanide-m-chlorophenylhydrazone, potassium laurate,
      or potassium fluoride inhibited acid production at lower but not at higher pH
      values. Inhibition by carbonyl cyanide-m-chlorophenylhydrazone and fluoride was
      found to be fully reversible at pH 8.0 when compared to control cells. In
      contrast, laurate inhibited irreversibly at pH values of 6.0 and below. The acid
      tolerance of S. downeii was severely compromised by laurate, and this action
      could be useful in dental caries control.

PMID- 8156570
TI  - [Human gene therapy].
AB  - Human gene therapy is one of the promising approaches in treatment of genetic
      diseases and rapid development of molecular genetic methods is bringing this
      therapy in life. The article summarises the information about possibilities of
      this therapy, methods of gene transfer, first clinical experience and certain
      ethical aspects of this therapy.

PMID- 8156569
TI  - Arginine metabolism in the salivary glands of protein-deficient rats and its
      potential association with the oral microflora.
AB  - Salivary glands and their secretions play key roles in the prevention of dental
      diseases. The antibacterial and physicochemical properties of saliva are
      compromised in chronic malnutrition. The present study has examined the
      possibility that some malnutrition-induced changes in salivary gland function are
      potentially capable of promoting growth and metabolic activities of pathogenic
      oral microorganisms. Compared to well-fed controls, rats fed a 3% protein diet
      for 18 days showed a significant reduction (p < 0.001) in the submandibular gland
      arginase (L-arginine amidinohydrolase, EC 3.5.3.1) activity. Associated with the
      latter finding was a marked increase (+85%) in the glandular level of free
      arginine, this basic amino acid accounting for 12.2% of the total essential amino
      acids as compared with a figure of only 4.6% for the controls. The total free
      amino acid pool in whole saliva was relatively unaffected by malnutrition, but
      the levels of the basic amino acids arginine and histidine were marginally
      increased. Many oral bacterial species, some of which are dominant plaque
      microorganisms, utilize the arginine deiminase (EC 3.5.3.6) pathway. Thus,
      increased availability of free arginine from salivary glands offers a plausible
      explanation for the frequently reported observation of differential overgrowth of
      several potentially pathogenic microorganisms including some mutants streptococci
      in protein-deficient laboratory animals and may well apply to similar findings in
      malnourished populations in Third World countries.

PMID- 8156571
TI  - [Coronary endarterectomy: has the time come for randomized evaluation of clinical
      research?].
AB  - The authors review contemporary and hitherto not uniform views on the clinical
      impact of endarterectomy in the surgical treatment of diffuse coronary disease.
      Exact evaluation of this problem is still lacking. The authors suggest an
      original, prospective project for the objective evaluation of this therapeutic
      method by a randomized study called PROCESS. Initial experience indicates that
      revascularization procedures with endarterectomy are in the early postoperative
      stage associated with a higher mortality and morbidity than conventional surgery
      using only bypasses without endarterectomy of diffusely altered coronary
      arteries. Hypothetically it is possible that the long-term fate of patients with
      more complete revascularization, i.e. with reconstruction of diffusely altered
      arteries, will be more favourable than the prognosis of patients with partial
      reconstruction of the coronary circulation. The objective of the proposed project
      is to test this hypothesis. This will be, however, possible only after a longer
      time interval.

PMID- 8156572
TI  - [Insulin resistance and insulin secretion in type II non-obese diabetics].
AB  - BACKGROUND: Glucose tolerance depends essentially on insulin secretion and its
      action in target tissues. Diabetes mellitus type II (insulin-nondependent
      diabetes) is a disease conditioned by a dysbalance between insulin secretion and
      effect; it has not been decided whether the cause is insulin resistance or
      impaired insulin secretion, although a defect of insulin secretion for the
      manifestation of the disease is generally accepted. The purpose of the submitted
      study was to assess to what extent insulin secretion and its effect after an oral
      glucose load and a hyperglycaemic clamp is affected in different groups of non
      obese patients with diabetes type II. METHODS AND RESULTS: The authors examined
      21 men with diabetes type II (age 41 +/- 2.6 years, BMI 26.2 +/- 3.2, HbA1,c 9.4
      +/- 2.9%) in the course of one year after detection of the disease, treated by
      diet alone. The second group was formed by 20 patients with diabetes type II (age
      46.1 +/- 3.6 years, BMI 26.0 +/- 2.1, HbA1,c 6.94 +/- 1.6%) who suffered from
      diabetes for 5-10 years and who were treated by diet alone. The third group was
      formed by 32 diabetics type II (age 51.8 +/- 6.1 years, BMI 26.7 +/- 2.2, HbA1,c
      8.7 1.2% +/-) who suffered from diabetes for 5-10 years and were treated with
      oral antidiabetics. The control group was formed by 42 healthy men matched for
      body weight and age (age 39.9 years, BMI 25.3, blood sugar level 4.8 mmol/l).
      Although the diabetic groups did not differ in the fasting blood sugar level (8.0
      8.29-8.2 mmol/l), the glycosylated haemoglobin HbA1,c level is lowest in the
      group of diabetics treated by diet alone, similarly as the rise of the blood
      sugar level 120 mins, following oral administration of 75 g of glucose (10.3
      mmol/l, as compared with 16.2 mmol/l and 15.5 mmol/l in the other groups). The
      authors found in all groups of diabetic patients, as compared with controls, a
      comparable drop of the insulin effect evaluated as the metabolic glucose
      clearance during an hyperinsulinaemic euglycaemic (5 mmol/l) or isoglycaemic
      (fasting blood sugar level) clamp, the insulin level being 75 microU/ml (controls
      10.9 +/- 3.3 ml/kg.min., first group 5.35 +/- 2.7 ml/kg.min., second group 5.47
      +/- 2.35 ml/kg.min., third group 5.38 +/- 2.1 ml/kg.min. The differences, as
      compared with controls, were significant in all groups, p < 0.01). At an insulin
      level of 1500 microU/ml the results are similar (controls 17.4 +/- 3.8
      ml/kg.min., as compared with 13.3 +/- 3.3 in the first group, 13.3 +/- 3.0 in the
      second group and 12.5 +/- 3.0 ml/kg.min. in the third group: statistical
      significance in all three groups, as compared with controls, is p < 0.05). The
      authors did not reveal any differences in the specific insulin bond to insulin
      receptors of erythrocytes. The total glucose consumption during an isoglycaemic
      clamp in diabetics and a euglycaemic clamp in controls did not differ. In all
      diabetic groups, as compared with controls, higher C peptide values and insulin
      values (IRI) were found on fasting and a slower rise and longer persistence of
      higher levels after oral glucose administration, although an inadequate secretory
      response during the hyperglycaemic clamp in diabetics is apparent.
      Hyperinsulinism was significantly higher in the second group. The number of
      insulin receptors on erythrocytes, the affinity for insulin, regardless whether
      the receptors were free or occupied, did not differ significantly between groups.
      CONCLUSIONS: All investigated groups of type II diabetics had a comparable degree
      of insulin resistance which did not depend on the duration of diabetes, its
      compensation or the type of treatment. Although impaired insulin action was
      proved, the total glucose utilization in relation to hyperglycaemia is not
      reduced. The differences in the degree of glucose intolerance in the investigated
      groups of diabetics type II depend on the degree of impairment of insulin
      secretion.

PMID- 8156573
TI  - [Body weight fluctuation in obese women and atherogenesis risk factors].
AB  - BACKGROUND: Hitherto published experimental and clinical studies provide
      controversial findings as regards the relations of risk factors of atherogenesis
      and ischaemic heart disease and variations of body weight. The objective of the
      present study was to find out whether variations of body weight in women with
      severe obesity influence the incidence of some other risk factors of
      atherogenesis. METHODS AND RESULTS: Two groups of obese women were examined. The
      group described as "weight cyclers" comprised 29 women where repeated variations
      of body weight were recorded, whereby at least two cycles of weight loss and
      subsequent gain were higher than 10 kg. The mean age of the group was 40.6 +/-
      1.6 years, the body weight 113.0 +/- 4.2 kg, the body mass index (BMI) 39.88 +/-
      1.48, the mean number of weight cycles (< 10 kg) was 2.38 +/- 0.11. The second
      group described as "non-weight cyclers" comprised 55 women whose body weight
      change, with the exception of pregnancy, at the age above 20 years did not exceed
      5 kg. The mean age of this group of women was 38.5 +/- 2.1 years, the body weight
      110.4 +/- 2.9 kg and BMI 39.31 +/- 0.98. The anthropometric indicators--ratio of
      lean body mass, the waist/hip ratio, the waist/thigh ratio, the sagittal diameter
      at the L4/L5 level did not differ in the two groups: an exception was only the
      centralization index which differed at the borderline of statistical significance
      (p < 0.05). The values of other risk factors are as follows: (the first figure
      refers to the "weight cyclers"). Systolic blood pressure 135.0 +/- 2.5 mmHg and
      135.9 +/- 2.4 mmHg resp., diastolic blood pressure 86.1 +/- 1.7 mmHg and 86.2 +/-
      1.5 mmHg resp., fasting serum insulin (IRI) 22.2 +/- 3.5 mU/l and 26.2 +/- 2.4
      mU/l resp., the fasting blood sugar level 5.30 +/- 0.17 mmol/l and 5.48 +/- 0.16
      mmol/l, total cholesterol 5.29 +/- 0.17 mmol/l and 5.53 +/- 0.13 mmol/l, HDL
      cholesterol 1.40 +/- 0.05 mmol/l and 1.30 +/- 0.04 mmol/l, triacylglycerols 1.92
      +/- 0.22 mmol/l and 2.10 +/- 0.22 mmol/l. The serum concentrations of free fatty
      acids (at 7.00 a.m., 1.00 p.m., 9 p.m.) did not differ in the two groups: 0.790
      +/- 0.058 mmol/l and 0.772 +/- 0.060 mmol/l at 7.00 a.m., 0.621 +/- 0.066 mmol/l
      and 0.641 +/- 0.051 mmol/l resp. at 1.00 p.m., 0.730 +/- 0.066 mmol/l and 0.810
      +/- 0.061 mmol/l resp. at 9.00 p.m. CONCLUSIONS: The increased flow of free fatty
      acids from intraabdominal fat depots is considered to be one of the factors
      mediating metabolic complications in the android type of obesity. Therefore the
      absence of any difference in fasting free fatty acid levels in both groups of
      investigated obese women suggests that variations in body weight do not
      participate in the increased risk of development of metabolic complications in
      women with severe obesity. Marked variations in body weight in women with severe
      obesity do not influence the incidence of the risk factors of atherogenesis.

PMID- 8156574
TI  - [The sorption effectiveness of Czech-manufactured hemoperfusion sorbents for
      amatoxins].
AB  - BACKGROUND: Haemoperfusion was introduced in the treatment of intoxications with
      Amanita phalloides in 1974. Haemoperfusion over active charcoal is used most
      frequently. The objective of the present study was to compare the sorption
      capacity of Czech haemoperfusion sorbents of the charcoal and resin type for
      amatoxins extracted from dried Amanita phalloides. METHODS AND RESULTS:
      Haemoperfusion sorbents on the basis of charcoal-Chemviron SC XII and on the
      basis of synthetic resin--Amberlite XAD 2 were used in experiments in vitro.
      Recirculation of an aqueous extract of Amanita phalloides over a haemoperfusion
      column with a volume of 400 ml located in a closed system took 4 hours. Amanitin
      levels (alpha and beta) were assessed by HPLC. Two-hour perfusion over Amberlite
      XAD led to removal of the entire amount of both amanitins from the aqueous
      solution. Four-hour perfusion over charcoal, however, reduced the original alpha
      amanitin level by 24% (p < 0.05) and of beta amanitin by 8% (change not
      significant). Extraction of alpha and beta amanitin by the resin sorbent varied
      between 0.95-1.00. The type of charcoal used, produced from the shells of
      coconuts, had a low extraction activity, cca 12%. CONCLUSIONS: The assembled
      results provide evidence that the synthetic resin Amberlite XAD 2 has a more than
      ten times greater sorption capacity, as compared with charcoal (Chemviron SC XII)
      and that in experiments in vitro it removes rapidly and effectively alpha and
      beta amanitin from an aqueous solution. Although during sorption of mycotoxins
      from plasma or blood the sorption rate and total capacity declines amberlite
      resins (Czech haemoperfusion column Hemabsorb A2) can be recommended for use in
      clinical toxicology.

PMID- 8156575
TI  - [The attitude of family members with polycystic kidney disease to the disease and
      presymptomatic testing].
AB  - BACKGROUND: The application of presymptomatic diagnosis of polycystic kidney
      disease (PKD) relies on satisfactory collaboration between the affected families
      and the team of health workers. The objective of the present study was to assess
      the initial level of knowledge of the disease and its hereditary character, the
      attitudes of families with PKD to presymptomatic and prenatal testing focused on
      methods of molecular genetics as well as attitudes to induced abortion if the
      gene of PKD is detected in the foetus. METHODS AND RESULTS: In a group of 104
      subjects who had genetic examinations on account of familial PKD by means of
      questionnaires knowledge of the diagnosis, clinical and genetic prognosis and
      attitudes to presymptomatic and prenatal genetic tests were investigated. About
      75% of the members of the group had adequate knowledge of the name of the disease
      and description of the clinical picture, 96.1% were informed on the hereditary
      character of the disease but only 1.9% knew details about the heredity. The scope
      of genetic risk was mentioned by some 30%, 51% were unable to express their
      opinion on the risk. A positive attitude to testing for the presence of the PKD
      gene was recorded in almost 100% if they themselves were concerned, 94% when
      their offspring under age was concerned but only 19.2% when the foetus was
      concerned. Only 5.3% of the respondents would agree with induced abortion in case
      of positive prenatal evidence of the PKD gene in the foetus and a few more
      respondents (14%) were opposed to abortion and some 80% were unable or unwilling
      to express their opinion. CONCLUSIONS: In members of families with PKD an
      important role is played by knowledge of clinical and genetic aspects of the
      disease. Genetic counselling must be part of comprehensive care and should always
      precede indication of molecular genetic methods (DNA analyses).

PMID- 8156576
TI  - [An epidemiological study on traffic accident in Guangzhou].
AB  - This report showed the general mortality of traffic accident and changes of its
      distribution from 1974 to 1990 in Guangzhou. The incidence rate per 10,000
      registered vehicles, mortality and injury had been tending to fall during the
      interval. Since 1987, the average rate of decrease per year was 24.27%. The type
      of collision between automobiles was in the majority. The rate of deaths and
      injuries per accident involved bicycles or pedestrians was the highest. The
      percentage of crash between automobile and non-automobile, that between
      automobile and bicycle, and that between automobile and pedestrian tended to rise
      in recent years. The result of this study indicated that the administration of
      traffic safety in Guangzhou had gained marked success in the last few years.
      Traffic accident has become one of the grave problems of social safety and public
      health along with the increase of population and vehicles in modernized city.

PMID- 8156577
TI  - [Investigations on the epidemiology of brucellosis in some villages
      (pasturelands) of Su Nan County, Gansu Province].
AB  - During April-May 1991, by using SAT. CFT. and Coomb's methods epidemiological
      surveillance on brucellosis among human beings and animals in some villages and
      pasturelands of Su Nan County was conducted. We found out that the serum brucella
      antibody was positive in 61 cases (19.06% out of 320 human beings) and 49 cases
      were diagnosed as brucellosis. We also made an investigation on 497 cattle and
      1989 sheep with SAT methods. The result showed that 15 sera showing a positive
      reaction all came from sheep. The rate was 0.75%.

PMID- 8156578
TI  - [Comparison between large bowel cancer in young people and that in middle-aged
      and old-aged people].
AB  - In order to understand the difference in risk factors of large bowel cancer in
      different age groups, a population-based case-control study including two age
      groups, one group with the age of < or = 40 (180 cases and 184 controls). And the
      other group with the age of > 40 (1148 cases and 1161 controls), was conducted in
      Shanghai. The study indicated that: 1. The patients of age > 40 with large bowel
      cancer had closer relationship with the environmental factors (esp. dietary and
      nutritional factors) than the patients of age < or = 40. 2. The familial genetic
      risk factor which affected development of the cancer in younger group was two
      fold higher than that in elder group. The results suggested that both genetic and
      environmental factors influenced the occurrence of the cancer, and the role of
      the genetic factor in < or = 40-yr group and that of the environmental factors in
      > 40-yr group appeared to be important.

PMID- 8156579
TI  - [Studies on the correlation of blood selenium and lung cancer. II. An analysis of
      serum selenium levels and influencing factors in patients with lung cancer].
AB  - This paper reports the serum selenium concentration in 100 cases of lung cancer
      patients and 100 healthy controls. The results showed that the serum selenium
      level in patients with lung cancer was significantly lower than that of controls.
      Serum selenium level in lung cancer patients was inversely related to the stage
      of cancer, the amount of tobacco abuse and the serum Cu level. It was positively
      correlated with patient's nutritional status and the serum albumin level. Serum
      selenium level was decreased with cancer progression and increased with disease
      remission. These results suggest that the lower serum selenium level in lung
      cancer patients was the result rather than the cause of cancer.

PMID- 8156580
TI  - [Meta-analysis of smoking and lung cancer in China: combined analysis of fifteen
      case-control studies].
AB  - In the present paper, 15 case-control studies on the relation between smoking and
      lung cancer in China were analyzed by means of Meta-analysis method. The
      cumulative cases and controls were 5703 and 5669, respectively. Peto's model and
      Der Simonian and Nan Laird model were applied to process data. The pooled OR
      (smoking vs no smoking) was 3.01 (95% CI: 2.63-3.46) in males and 2.32 (95% CI:
      2.02-2.66) in females. The PAR was 56.84% in males and 33.10% in females. There
      was significant dose-response relation between the amount of smoking, the years
      of smoking, the age at start of smoking and the OR for developing lung cancer.
      The pooled OR of squamous carcinoma was 4.79 (95% CI: 4.02-5.70), PAR was 65.44%.
      The pooled OR of adenocarcinoma was 1.02 (95% CI: 0.87-1.20), PAR was 0.99%.

PMID- 8156581
TI  - [Application of analytical hierarchy process in the evaluation of quality of
      management of infectious diseases].
AB  - We evaluated the quality of management of infectious diseases in hospitals with
      analytical hierarchy process (AHP). An attempt to work out assessing model for
      the management of infectious diseases by establishing a Goal Tree and groups of
      indices is presented. The rankings, indices and stresses in each assess of this
      model were established by the request of the content and quality of management of
      infectious diseases. The Consistent Index (C.I) was used to test whether the
      contrast rankings of the model were logical, making the logical judgement of
      evaluated factors quantitated. The results show that the model is scientific and
      feasible.

PMID- 8156582
TI  - [Analysis of malarial infection among technical personnel dispatched to Burkina
      Faso, West Africa].
AB  - Fifty-six technical personnel, who had been dispatched to carry out the Chinese
      aid project in Burkina Faso, West Africa (a highly prevalent area of malaria and
      infected by asexual from of plasmodium), developed malaria within one year after
      the repatriation from that country. The number of paroxysm of this disease per
      individual varied from one to six, with an average of 2.8.

PMID- 8156583
TI  - [Application of the time-resolved immunofluorometric assay in the detection of
      viruses].
AB  - Two systems of time-resolved immunofluorometric assay (TR-IFMA), i.e., LKB system
      detection of viruses. The viruses detected were mainly adenovirus, influenza
      virus, parainfluenza virus, respiratory syncytial virus rotavirus, hepatitis B
      virus, human immunodeficiency virus, rubella virus, etc. Compared with methods of
      ELISA and RIA, TR-IFMA has the merits of high sensitivity, specificity and
      consistency with clinical diagnosis. The low detection limit of virus antigen by
      TR-IFMA is between 10-100 pg. The application of dual-label TR-IFMA also showed
      good effect. TR-IFMA can also be used in the detection of viral nucleic acids.
      The target region detected may reach the level of pg.

PMID- 8156584
TI  - [Application of SP-RIA in the antibody surveillance and serologic diagnosis of
      epidemic cerebrospinal meningitis].
AB  - This paper reports the effectiveness of SP-RIA in the antibody surveillance on
      population, the observation of immune persistence after vaccination with Group A
      Neisseria meningococcal capsular polysaccharide vaccine, as well as its use in
      the serological diagnosis of Neisseria meningitis. In comparison with other
      assays used presently, SP-RIA might be better and more sensitive for quantitative
      assay of the antibody. The results showed the practical value of SP-RIA in the
      study of epidemiology and serology of epidemic cerebrospinal meningitis.

PMID- 8156585
TI  - [Influential factors of immunologic effect of poliovirus vaccines].

PMID- 8156586
TI  - The basics of basal transcription by RNA polymerase II.

PMID- 8156587
TI  - Cyclin E controls S phase progression and its down-regulation during Drosophila
      embryogenesis is required for the arrest of cell proliferation.
AB  - Most cells of the dorsal epidermis exit from the mitotic cycle after division 16
      in Drosophila embryogenesis. This exit is dependent on the down-regulation of
      Drosophila cyclin E (DmcycE) during the final mitotic cycle. Ectopic expression
      of DmcycE after the final mitosis induces entry into S phase and reaccumulation
      of G2 cyclins and results in progression through a complete additional cell
      cycle. Conversely, analyses in DmcycE mutant embryos indicate that cyclin E is
      required for progression through S phase of the mitotic cycle. Moreover,
      endoreplication, which occurs in late wild-type embryos in the same pattern as
      DmcycE expression, is not observed in the mutant embryos. Therefore, Drosophila
      cyclin E, which forms a complex with the Dmcdc2c kinase, controls progression
      through S phase and its down-regulation limits embryonic proliferation.

PMID- 8156588
TI  - Transcription: in tune with the histones.
AB  - The regulation of transcription in eukaryotes relies upon the histone proteins in
      several essential ways. The incorporation of the binding sites for the basal
      transcriptional machinery into nucleosomes serves to repress transcription.
      Specific regulatory molecules other than the basal transcriptional machinery
      exist that can associate with nucleosomal DNA and initiate a chain of events that
      disrupt repressive histone-DNA complexes. The main players in this story have
      been defined physically and genetically and include positioned nucleosomes,
      interactions of the histone tetramer (H3-H4)2 with DNA, the N-terminal tails of
      histones H3 and H4, and a large general activator complex. How they fit together
      biochemically is yet to be defined. The genetic data demonstrate that the
      disruption of histone-DNA complexes plays a major role in the induction of
      transcription from many genes. However, not all genes are repressed by nucleosome
      assembly: certain promoters make use of the staged assembly of chromatin in vivo
      and a rapid and tight association of transacting factors with promoter elements
      to remain constitutively active. Moreover, nucleosome assembly is not necessarily
      repressive, since the folding of DNA by the histones can facilitate the
      activation of genes by bringing widely separated regulatory elements into
      juxtaposition. Thus, histones provide the necessary infrastructure for the
      correct and efficient operation of the transcriptional machinery; however, their
      exact contributions to the transcriptional regulation of an individual gene may
      depend on the spatial distribution of regulatory elements, the transcription
      factors involved, and the three-dimensional folding of DNA that they direct.

PMID- 8156589
TI  - The expression of Vpre-B/lambda 5 surrogate light chain in early bone marrow
      precursor B cells of normal and B cell-deficient mutant mice.
AB  - Precursor B (pre-B) cells in bone marrow of normal and B cell-deficient mutant
      mice were analyzed for the expression of Vpre-B/lambda 5 surrogate light chain
      (SL). The surface expression of SL is confined to the early stages (pro-B and pre
      B-I) of pre-B cell development and becomes undetectable once mu heavy chain
      (microH) is produced. The cell-cycle analysis revealed that cytoplasmic microH+
      large cells (large pre-B-II), approximately 30% of which coexpressed SL in the
      cytoplasm, were most actively cycling, whereas cytoplasmic microH+ small cells
      (small pre-B-II) were SL- and not in cycle. The analysis of pre-B cells in B cell
      deficient mice suggests that the large pre-B-II stage is a critical step for the
      selection and amplification of cells carrying functionally rearranged microH
      genes.

PMID- 8156590
TI  - Transcription factors IIE and IIH and ATP hydrolysis direct promoter clearance by
      RNA polymerase II.
AB  - Using a defined RNA polymerase II (pol II) transcription system, we have
      investigated the roles of basal factors at discrete stages during the
      transcription cycle (e.g., initiation, promoter clearance, and transcript
      elongation). Abortive initiation assays revealed that TATA-binding protein,
      transcription factors TFIIB and TFIIF, and pol II were necessary and sufficient
      to form functional initiation complexes on both linear and supercoiled templates.
      By contrast, TFIIE, TFIIH, and ATP hydrolysis were additionally required during
      promoter clearance from linear templates, while negative supercoiling obviated
      the need for these auxiliary factors. Furthermore, TFIIE, TFIIH, and supercoiling
      were not required during elongation. Our results suggest a role for TFIIH
      associated helicase activity or supercoiling during promoter clearance rather
      than open complex formation. These results establish abortive initiation as a
      useful assay for studying functional initiation complex formation in defined
      eukaryotic transcription systems and provide a framework for investigating
      regulation at different stages of the eukaryotic transcription cycle.

PMID- 8156591
TI  - Coordination of leading and lagging strand DNA synthesis at the replication fork
      of bacteriophage T7.
AB  - We have used the T7 DNA replication system to examine coordination of leading and
      lagging strand synthesis at a replication fork. The 63 kd gene 4 protein provides
      both helicase and primase activities; we demonstrate that primer synthesis
      inhibits helicase activity on a synthetic replication fork. Lagging strand DNA
      synthesis by a complex of gene 4 protein and T7 DNA polymerase decreases the rate
      of leading strand synthesis. Both leading and lagging strand synthesis are
      resistant to dilution of the replication proteins, and to challenge with heparin.
      Furthermore, dilution does not increase the average length of Okazaki fragments.
      We propose that leading and lagging strand synthesis at a T7 replication fork are
      coupled and that the replication proteins are recycled.

PMID- 8156592
TI  - The human mutator gene homolog MSH2 and its association with hereditary
      nonpolyposis colon cancer.

PMID- 8156593
TI  - Basic-helix-loop-helix transcription factor and sterol sensor in a single
      membrane-bound molecule.

PMID- 8156594
TI  - Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA
      recognition with tethered DNA-binding modules.
AB  - The structure of an Oct-1 POU domain-octamer DNA complex has been solved at 3.0 A
      resolution. The POU-specific domain contacts the 5' half of this site (ATGCAAAT),
      and as predicted from nuclear magnetic resonance studies, the structure, docking,
      and contacts are remarkably similar to those of the lambda and 434 repressors.
      The POU homeodomain contacts the 3' half of this site (ATGCAAAT), and the docking
      is similar to that of the engrailed, MAT alpha 2, and Antennapedia homeodomains.
      The linker region is not visible and there are no protein-protein contacts
      between the domains, but overlapping phosphate contacts near the center of the
      octamer site may favor cooperative binding. This novel arrangement raises
      important questions about cooperativity in protein-DNA recognition.

PMID- 8156595
TI  - Essential role for KH domains in RNA binding: impaired RNA binding by a mutation
      in the KH domain of FMR1 that causes fragile X syndrome.
AB  - The KH domain is an evolutionarily conserved sequence motif present in many RNA
      binding proteins, including the pre-mRNA-binding (hnRNP) K protein and the
      fragile X mental retardation gene product (FMR1). We assessed the role of KH
      domains in RNA binding by mutagenesis of KH domains in hnRNP K and FMR1.
      Conserved residues of all three hnRNP K KH domains are required for its wild-type
      RNA binding. Interestingly, while fragile X syndrome is usually caused by lack of
      FMR1 expression, a previously reported mutation in a highly conserved residue of
      one of its two KH domains (Ile-304-->Asn) also results in mental retardation. We
      found that the binding of this mutant protein to RNA is severely impaired. These
      results demonstrate an essential role for KH domains in RNA binding. Furthermore,
      they strengthen the connection between fragile X syndrome and loss of the RNA
      binding activity of FMR1.

PMID- 8156596
TI  - Evidence that random and imprinted Xist expression is controlled by preemptive
      methylation.
AB  - The mouse Xist gene is expressed exclusively from the inactive X chromosome and
      may control the initiation of X inactivation. We show that in somatic tissues the
      5' end of the silent Xist allele on the active X chromosome is fully methylated,
      while the expressed allele on the inactive X is completely unmethylated. In
      tissues that undergo imprinted paternal Xist expression and imprinted X
      inactivation, the paternal Xist allele is unmethylated, and the silent maternal
      allele is fully methylated. In the male germline, a developmentally regulated
      demethylation of Xist occurs at the onset of meiosis and is retained in mature
      spermatozoa. This may be the cause of imprinted expression of the paternal Xist
      allele. A role for methylation in the control of Xist expression is further
      supported by the finding that in differentiating embryonic stem cells during the
      initiation of X inactivation, differential methylation of Xist alleles precedes
      the onset of Xist expression.

PMID- 8156597
TI  - Transcriptional activation: a complex puzzle with few easy pieces.

PMID- 8156598
TI  - SREBP-1, a membrane-bound transcription factor released by sterol-regulated
      proteolysis.
AB  - Sterol regulatory element-binding protein 1 (SREBP-1), a member of the basic
      helix-loop-helix-leucine zipper (bHLH-ZIP) family of transcription factors, is
      synthesized as a 125 kd precursor that is attached to the nuclear envelope and
      endoplasmic reticulum. In sterol-depleted cells, the membrane-bound precursor is
      cleaved to generate a soluble NH2-terminal fragment (apparent molecular mass, 68
      kd) that translocates to the nucleus. This fragment, which includes the bHLH-ZIP
      domain, activates transcription of the genes for the LDL receptor and HMG CoA
      synthase. Sterols inhibit the cleavage of SREBP-1, and the 68 kd nuclear form is
      rapidly catabolized, thereby reducing transcription. ALLN, an inhibitor of
      neutral cysteine proteases, blocks the breakdown of the 68 kd form and
      superinduces sterol-regulated genes. Sterol-regulated proteolysis of a membrane
      bound transcription factor provides a novel mechanism by which transcription can
      be regulated by membrane lipids.

PMID- 8156599
TI  - Cyclic GMP and calcium mediate phytochrome phototransduction.
AB  - We have previously used single-cell assays in a phytochrome-deficient tomato
      mutant to demonstrate that phytochrome signaling involves heterotrimeric G
      proteins, calcium, and calmodulin. While G protein activation could stimulate
      full chloroplast development and anthocyanin pigment biosynthesis, calcium and
      calmodulin could not induce anthocyanins and were only able to stimulate the
      development of immature chloroplasts lacking cytochrome b6f and photosystem I
      core components. We now report that cyclic GMP is able to trigger the production
      of anthocyanins, and that a combination of cyclic GMP with calcium can induce the
      development of fully mature chloroplasts containing all the photosynthetic
      machinery. Furthermore, using reporter genes for these different pathways (cab
      gus, chs-gus, and fnr-gus) we demonstrate that cGMP and calcium act primarily by
      modulating gene expression.

PMID- 8156600
TI  - A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated
      by G protein beta gamma subunits.
AB  - Phosphoinositide 3 kinase (PI3K) is a key signaling enzyme implicated in receptor
      stimulated mitogenesis, oxidative bursting in neutrophils, membrane ruffling, and
      glucose uptake. A PI3K has already been purified, cloned, and shown to be
      regulated by receptors that act via tyrosine kinase-dependent regulatory
      mechanisms. We report that an immunologically, pharmacologically, and
      chromatographically distinct form of PI3K activity present in neutrophils and
      U937 cells is specifically activated by G protein beta gamma subunits. This data
      suggests PI3Ks conform to the paradigm set by receptor regulation of
      phosphoinositidase Cs: different receptor transduction systems specifically
      regulate dedicated isoforms of effector protein.

PMID- 8156601
TI  - Where transcription meets repair.

PMID- 8156602
TI  - The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity
      in the early C. elegans embryo.
AB  - The sister blastomeres ABp and ABa are equipotent at the beginning of the 4-cell
      stage in C. elegans embryos, but soon become committed to different fates. We
      show that the glp-1 gene, a homolog of the Notch gene of Drosophila, functions in
      two distinct cell-cell interactions that specify the ABp and ABa fates. These
      interactions both require maternal expression of glp-1. We show that a second
      maternal gene, apx-1, functions with glp-1 only in the specification of the ABp
      fate and that apx-1 can encode a protein homologous to the Delta protein of
      Drosophila. Our results suggest how interactions mediated by glp-1 and apx-1
      contribute to the establishment of the dorsal-ventral axis in the early C.
      elegans embryo.

PMID- 8156603
TI  - Comparison of the urinary metabolite profiles of hexachlorobenzene and
      pentachlorobenzene in the rat.
AB  - The urinary metabolite profile of hexachlorobenzene (HCB) and pentachlorobenzene
      (PCBz) in the rat is compared after dietary exposure for 13 weeks. Both HCB and
      PCBz are oxidized to pentachlorophenol (PCP) and tetrachlorohydroquinone (TCHQ),
      which were the only two mutual metabolites formed. Additional urinary metabolites
      of HCB are N-acetyl-S(pentachlorophenyl)cysteine (PCTP-NAC), which appeared to be
      quantitatively the most important product, and mercaptotetrachlorothioanisole
      (MTCTA), which was excreted as a glucuronide. PCBz is more extensively
      metabolized to the major metabolites 2,3,4,5-tetrachlorophenol (TCP),
      mercaptotetrachlorophenol (MTCP) and the glucuronide of pentachlorothiophenol
      (PCTP), and the minor metabolites methylthiotetrachlorophenol (MeTTCP),
      hydroxytetrachlorophenyl sulphoxide (HTCPS), and bis(methylthio)-trichlorophenol
      (bis-MeTTriCP). The biotransformation of HCB and PCBz was modulated by selective
      inhibition of cytochrome P450IIIA in rats which received combined treatment of
      HCB or PCBz with triacetyloleandomycin (TAO). Rats receiving this diet had a
      strongly diminished excretion of both PCP and TCHQ, as compared to rats fed HCB
      or PCBz alone, indicating the involvement of P450IIIA in the oxidation of both
      compounds. However, the excretion of 2,3,4,5-TCP was not diminished by co
      treatment of rats with PCBz and TAO, indicating that: (i) the oxidation of PCBz
      to PCP and 2,3,4,5-TCP does not proceed via a common intermediate; and (ii)
      oxidation of PCBz to 2,3,4,5-TCP is not mediated by P450IIIA. Co-treatment of
      rats with PCBz and TAO had a differential effect on the excretion of sulphur
      containing metabolites, resulting in a decrease in the excretion of PCTP
      glucuronide, whereas no change was observed in the excretion of MTCP, as compared
      to rats receiving PCBz alone. The observed differences in HCB and PCBz
      metabolites clearly deserve further in vitro studies to elucidate their origin.

PMID- 8156604
TI  - Reduction and binding of arsenate and dimethylarsinate by glutathione: a magnetic
      resonance study.
AB  - By observing the chemical shifts of the proton and carbon-13 nuclei of reduced
      glutathione, the interactions of arsenate, arsenite and dimethylarsinate with
      this tripeptide have been characterized. These spectral studies show the
      reduction and complexation of arsenic to be a two-step process. Initially, the
      oxidation of 2 mol of glutathione reduces arsenate to arsenite. Then, 3 mol of
      glutathione are consumed in the formation of a glutathione-arsenite complex.
      Similar experiments with arsenite identified a (glutathione)3-arsenite complex;
      however, no oxidized glutathione was detected. The arsenite binding site in the
      glutathione-arsenite complex is the cysteinyl sulfhydryl. The glutathione
      arsenite complex is stable over the pH range from 1.5 to 7.0-7.5. At higher pH,
      dissociation occurs releasing reduced glutathione. For a glutathione to
      dimethylarsinate ratio of 3, oxidized glutathione is also coupled with a
      reduction to trivalent dimethylarsinous acid, prior to the formation of a 1:1
      glutathione-dimethylarsinite complex. The role of reduced glutathione in the
      metabolism of arsenic is consistent with the previously described effects of this
      agent on the organismic toxicity of arsenic.

PMID- 8156605
TI  - Regiospecific reduction of polycyclic aromatic quinones by rabbit liver
      dihydrodiol dehydrogenases.
AB  - Dihydrodiol dehydrogenase (DDH) isoenzymes were purified from rabbit liver (Klein
      et al., Eur. J. Biochem., 205 (1992) 1155), and the major forms CF-1, CF-5 and CM
      2 were tested for their substrate specificity with dihydrodiol and quinone
      metabolites of polycyclic aromatic hydrocarbons. CF-5, which was shown to
      correspond to aldehyde reductase in rabbit liver, was found to efficiently
      oxidize aromatic dihydrodiol metabolites (phenanthrene-1,2-dihydrodiol,
      benz[a]anthracene-3,4-dihydrodiol) while CF-1, corresponding to carbonyl
      reductase, and CM-2 were much less active. All three enzyme forms were found to
      reduce polycyclic K-region o-quinones of benz[a]anthracene, chrysene and
      benzo[a]pyrene. CF-1 was the least active, and CM-2 was the most active form with
      reaction velocities of > 10 mumol/min.mg protein. Among a range of synthetic
      quinones tested, benz[a]anthracene-8,9-quinone and benzo[a]pyrene 9,10-quinone
      were also good substrates for the three enzymes, as well as p-benzoquinone and
      naphthalene-1,4-quinone. The reduction of polycyclic o-quinones, but not of p
      benzoquinone, by enzyme CM-2 was accompanied by the oxidation of large amounts of
      NADPH and the consumption of molecular oxygen which is indicative of a redox
      cycling process. Thus, the formation of catechol metabolites from dihydrodiols
      and o-quinones may be catalyzed by the same enzymes in rabbit liver, and the
      reaction rate of the enzymatic reduction is strongly dependent on the structural
      type of the polycyclic quinone.

PMID- 8156606
TI  - Inhibition of DNA topoisomerase I activity by 2',5'-oligoadenylates and
      mismatched double-stranded RNA in uninfected and HIV-1-infected H9 cells.
AB  - 2',5'-Oligoadenylates (2-5As) inhibit the type I DNA topoisomerase activity both
      in uninfected and HIV-1-infected human T cell line H9 as well as the purified
      enzyme (calf thymus). Topoisomerase I activity was determined by measuring the
      relaxation of negatively supercoiled pBR322 DNA. Inhibition of topoisomerase I by
      2-5A depends on the chain length of the oligomer and the presence of 5'
      phosphate. The 5'-triphosphate of the 2-5A hexamer was most active (almost total
      inhibition of DNA relaxation at 10 microM concentration); the 2-5A core trimer
      (at 100 microM) displayed no significant effect. In crosslinking and
      immunoprecipitation experiments we present evidence that 2-5A (32P-labelled 2-5A
      derivative, ppp(A2'p)3 A[32P]pCp) is able to bind to nuclear topoisomerase I. The
      mismatched dsRNA, poly(I).poly(C12U) (Ampligen), exhibited a strong anti-HIV-1
      activity. However, our data show that this antiviral effect is not related to
      topoisomerase I inhibition. On the other hand, we did observe the production of
      longer oligomers of 2-5A in cells treated with poly(I).poly(C12U). It remains
      speculative, whether the in vivo effect could be catalyzed by this activity of
      poly(I).poly(C12U). In addition we could show that 2-5A also inhibits
      topoisomerase I activity associated with isolated HIV-1 particles.

PMID- 8156607
TI  - Morphologic and metabolic changes in rat osteoblast cultures during the dark
      reaction with 8-methoxypsoralen.
AB  - The dark reaction of 8-methoxypsoralen (8-MOP) with cultured rat osteoblasts did
      not cause significant changes in cellular replication rates or in the synthesis
      of RNA and proteins. Microscopic examination, however, revealed that the dark
      reaction resulted in massive accumulation of perinuclear lipids and in the
      statistically significant enhancement of alkaline phosphatase activity. A sharp,
      and statistically significant, upsurge of lipid synthesis in osteoblasts preceded
      microscopically detectable accumulation of lipids and occurred only during the
      initial, but not during the subsequent stages of the dark reaction. These results
      suggest that in the course of the dark reaction the plasma membrane of
      osteoblasts is a target of psoralen.

PMID- 8156609
TI  - [Prevention and treatment of oral candidiasis with cortex cinnamon solution].

PMID- 8156608
TI  - [Child neuroticism and its influential factors].

PMID- 8156610
TI  - [Guangzhou yuchuangjia in the treatment of bedsore].

PMID- 8156611
TI  - [Using method to stimulate enthusiasm of the nursing staff].

PMID- 8156612
TI  - [Examination of nurses one year after graduation].

PMID- 8156613
TI  - [Nursing management during warm heart surgery].

PMID- 8156614
TI  - [Clinical application of Glasgow coma scale].

PMID- 8156615
TI  - [Curative effect of high energy elemental diet for burn patients].

PMID- 8156616
TI  - [Nursing care of maxillary sinus endoscopy].

PMID- 8156617
TI  - [Anti-xerostomic paste used for nasopharyngeal cancer undergoing radiotherapy].

PMID- 8156618
TI  - [Treating chronic dacryocystitis with metronidazole].

PMID- 8156619
TI  - [Evaluation of the effect of 5 kinds of orthodontic bonding agents].

PMID- 8156620
TI  - [Nursing care of chronic cerebellar stimulation in treating epilepsy].

PMID- 8156621
TI  - [Classification of mental disorders caused by cerebral infarction and its nursing
      care].

PMID- 8156622
TI  - [Addition of psychology for nursing education].

PMID- 8156623
TI  - ATP-sensitive K+ channels mediate dilatation of cerebral arterioles during
      hypoxia.
AB  - We tested the hypothesis that dilatation of cerebral arterioles during hypoxia is
      mediated by activation of ATP-sensitive K+ channels. The diameter of pial
      arterioles was measured through a closed cranial window in anesthetized rabbits.
      Topical application of aprikalim (10(-6) mol/L), a direct activator of ATP
      sensitive K+ channels, dilated pial arterioles by 18 +/- 3% (mean +/- SEM).
      Glibenclamide (10(-6) mol/L), an inhibitor of ATP-sensitive K+ channels,
      virtually abolished aprikalim-induced vasodilatation. When arterial PO2 was
      reduced from 129 +/- 3 to 25 +/- 1 mm Hg, the diameter of cerebral arterioles
      increased by 66 +/- 9% (P < .05). Glibenclamide inhibited dilatation of pial
      arterioles during hypoxia by 46 +/- 5% (P < .05). In contrast, vasodilatation in
      response to sodium nitroprusside was not altered by glibenclamide. Topical
      application of adenosine (10(-4) mol/L) increased arteriolar diameter by 21 +/-
      4%. Glibenclamide did not affect adenosine-induced vasodilatation. These findings
      suggest that dilatation of cerebral arterioles in response to hypoxia is
      mediated, in part, by activation of ATP-sensitive K+ channels.

PMID- 8156624
TI  - Cardiovascular development. Prospects for a genetic approach.
AB  - Genetics is a powerful tool, especially when used in combination with embryology,
      in the seeking of genes necessary for assembly of the cardiovasculature. The
      first questions must address the types of cellular decisions that are made during
      development. As for simpler systems in C elegans and D melanogaster, the lineage
      and cell-fate decisions of the cardiovascular progenitors need to be assessed. In
      addition it is likely that new paradigms will emerge for multicellular assembly.
      The study of cardiovascular mutations will define individual genetic steps that
      define organotypic decisions. A genetic approach is a natural extension of
      embryology, physiology, and anatomy, fields of great sophistication with regard
      to the cardiovasculature, because, like them, it focuses on integrative biology
      and on the intact organism. The zebrafish is particularly well suited to a
      combination genetic-embryologic study of the fashioning of the cardiovasculature.

PMID- 8156625
TI  - cis-regulatory elements and trans-acting factors directing basal and cAMP
      stimulated human renin gene expression in chorionic cells.
AB  - Much knowledge was accumulated in the regulation of plasma renin activity and
      renin secretion during recent years. However, the mechanisms of renin gene
      transcription, especially for the human gene, have been poorly studied because of
      the lack of cell lines expressing renin. Cells derived from chorion tissue were
      used to study renin gene transcription because these cells express renin and
      regulate renin secretion in a similar way to JG cells. The present study was
      performed to determine the cis-regulatory elements and the trans-acting factors
      involved in human renin gene expression using chorionic cells. Transient DNA
      transfections were performed with various constructs containing the 5'-flanking
      region of the human renin gene. 5'-Deletion analysis of the human renin promoter
      (from -2616 to -67 bp) revealed the presence of two proximal negative cis
      regulatory elements between -374 and -273 bp and between -273 and -137 bp. These
      elements were not present in a non-renin-producing cell line, JEG-3 cells. DNase
      I footprinting revealed that two sequences located within these regions bind
      trans-factors present in chorionic cellular nuclear extract: AGE3-like sequence (
      293/-273) and apolipoprotein A1 regulatory protein-1-like sequence (-259/-245).
      The first 110 bp of the renin promoter were sufficient to direct specific
      expression in chorionic cells and contained two footprints sharing homology with
      ets (-29/-6) and pituitary-specific factor (Pit-1) (-70/-62) sequences.
      Furthermore, one footprint (-234/-214) contained the sequence TAGCGTCA, which
      shares strong homology to the cAMP-responsive element (CRE) binding site. Gel
      shift analysis showed specific DNA/protein complexes within this region, which
      were displaced by the somatostatin consensus CRE. Finally, luciferase analysis of
      5'-deletion mutant revealed that -273 to +16 bp of the renin promoter was
      sufficient to confer complete forskolin stimulation, whereas deletion to -130
      (deletion of the CRE) decreased cAMP responsiveness by 50% and those to -67 bp
      (deletion of the CRE and Pit-1-like sequences) suppressed it. Thus, these latter
      two sequences probably act together to confer complete cAMP responsiveness.

PMID- 8156626
TI  - Hyperplastic growth of aortic smooth muscle cells in renovascular hypertensive
      rabbits is characterized by the expansion of an immature cell phenotype.
AB  - Smooth muscle cells (SMCs) of rabbit aorta undergo marked changes in myosin
      isoform content during development. Analysis of nonmuscle myosin composition at
      the protein level has permitted the identification of three phases in the SMC
      differentiation process: fetal, postnatal, and adult. Using monoclonal antibodies
      specific for smooth muscle and nonmuscle myosins and extra domain A of
      fibronectin as well as cDNA probes for platelet-derived growth factors (PDGF) and
      various procollagens, we have evaluated the differentiation pattern of aortic
      SMCs in two-kidney, one-clip hypertensive rabbits. Morphometric and bromo
      deoxyuridine studies indicate that hypertrophy of aortic media along with intimal
      thickening occurring in hypertensive animals is due to SMC hyperplasia. Western
      blotting experiments performed on aortic specimens from hypertensive animals with
      antimyosin antibodies revealed the appearance of a myosin isoform pattern of the
      "immature" type. Immunofluorescence tests showed that these cells are localized
      in the thickened intima or distributed in the underlying media (sparsely or in
      groups). Similarly, the fibronectin variant showing the extra domain A, peculiar
      to "phenotypically modulated" SMCs, appeared in intimal thickening, and its
      expression followed the time course of nonmuscle myosin expression. Counting of
      postnatal-type SMCs in the aortic media revealed that this cell population
      increases markedly with hypertension (2- up to 15-fold at 4 months) and then
      declines to near control level in 8-month hypertensive rabbits. Diminution of
      postnatal-type SMCs at later stages of hypertension was temporally correlated
      with the slowing down of aortic wall hypertrophy. Average levels of mRNAs, as
      determined by densitometric analysis in aortas from 1- and 2.5-month hypertensive
      rabbits, showed an increased expression for PDGF beta receptor (up to twofold),
      procollagen type I (alpha 1, threefold), procollagen type III (alpha 1, twofold),
      and fibronectin (up to threefold) compared with controls. Conversely, the steady
      state levels of mRNAs for PDGF (A and B chain), PDGF alpha receptor, TGF-beta 1,
      and procollagen type IV (alpha 1) did not increase significantly. These results
      provide evidence that in adult renovascular hypertensive rabbits, the
      hyperplastic growth of aortic SMCs is accompanied by the expansion of an
      "immature" cell phenotype characteristic of the early stages of development.

PMID- 8156627
TI  - Anisotropy of water diffusion in the myocardium of the rat.
AB  - Pulsed field gradient nuclear magnetic resonance methods combined with nuclear
      magnetic resonance imaging were used to determine the water diffusion anisotropy
      in perfused rat hearts at 37 degrees C. It was found that the observed diffusion
      coefficient D(app) (apparent diffusion coefficient) depends on the orientation of
      the applied gradient g. When g is parallel to the epicardial surface, the
      observed diffusivity is D(app) parallel = 1.8 +/- 0.4 x 10(-9) m2.s-1, whereas
      when g is perpendicular to it, diffusivity is D(app) perpendicular = 2.5 +/- 0.5
      x 10(-9) m2.s-1. To better characterize this directional dependence, images of
      the second-order diffusion tensor D of the myocardium were obtained. These data
      demonstrate several essential features of cardiac myoarchitecture, including the
      helicity of fiber orientation with respect to the ventricular axis and the
      variation of fiber pitch angle with transmural depth. Diffusion anisotropy may be
      quantified in a coordinate-independent manner by the eigenvalues of the diffusion
      tensor. In the myocardial midwall, these eigenvalues were E1 = 3.29 +/- 0.57, E2
      = 2.01 +/- 0.42, and E3 = 0.77 +/- 0.58 x 10(-9) m2.s-1 (mean +/- SD). These data
      suggest that myocardial water diffusion is essentially unrestricted parallel to
      the myofibers. They further show that failure to measure the complete diffusion
      tensor may lead to substantial underestimates of diffusion anisotropy in the
      myocardium.

PMID- 8156628
TI  - Stunned myocardium after rapid correction of acidosis. Increased oxygen cost of
      contractility and the role of the Na(+)-H+ exchange system.
AB  - Left ventricular (LV) contractile dysfunction during acidosis has been reported
      to be almost reversible in crystalloid-perfused hearts after correction of
      acidosis. In contrast, we have found that, in blood-perfused hearts, contractile
      function is paradoxically depressed after correction of acidosis with a transient
      overshoot of contractility during the recovery of pH. To clarify the mechanism of
      this phenomenon, we measured the LV contractility index (Emax) and the relation
      between myocardial oxygen consumption (VO2) and systolic pressure-volume area
      (PVA, a measure of the LV total mechanical energy) before and after induction and
      rapid correction of acidosis by CO2 loading (pH 7.00) and unloading in 13 excised
      cross-circulated canine hearts. During the rapid correction of acidosis in six
      control hearts, a severe transient overshoot of Emax (404% of acidosis) occurred.
      However, after correction of acidosis, Emax and PVA were lower than the
      preacidosis values by 46% (P < .01) and 44% (P < .01) at the same LV volume. When
      the preacidosis Emax level was restored by Ca2+ infusion, the VO2 intercept (PVA
      independent VO2) of the linear VO2-PVA relation exceeded the control value by 18%
      (P < .05) with an unchanged slope. In addition, the oxygen cost of contractility,
      defined as the slope of the relation between PVA-independent VO2 and Emax,
      increased by 83% (P < .01) after correction of acidosis, indicating that
      postacidosis myocardium requires higher VO2 for nonmechanical activities for a
      unit increase in Emax. Then, we hypothesized that these mechanoenergetic
      disorders after rapid correction of acidosis would result from Ca2+ overload via
      accelerated Na(+)-Ca2+ exchange due to the heavily operating Na(+)-H+ exchange
      system at the time of rapid pH recovery. To examine this hypothesis,
      dimethylamiloride, a selective Na(+)-H+ exchange inhibitor, was administered just
      before the correction of acidosis in the other seven hearts. The administration
      of dimethylamiloride completely prevented both the mechanical and energetic
      disorders after correction of acidosis. We conclude that rapid recovery of pH
      paradoxically depresses myocardial contractility and increases the oxygen cost of
      contractility through an activation of the Na(+)-H+ exchange system.

PMID- 8156629
TI  - The relative importance of myocardial energy metabolism compared with ischemic
      contracture in the determination of ischemic injury in isolated perfused rabbit
      hearts.
AB  - The mechanical effects of ischemic contracture may be important in the
      development of irreversible cellular damage as it increases mechanical stress on
      sarcolemmal membranes and restricts endocardial perfusion. To assess the relative
      importance of these mechanical effects compared with decreased energy supply in
      the development of irreversible injury, the effects of inhibiting ischemic
      contracture with 2,3-butanedione monoxime (BDM), an agent that disrupts
      excitation-contraction coupling, were delineated in isovolumically contracting
      isolated rabbit hearts. Administration of 20 mmol/L BDM in 12 hearts subjected to
      60 minutes of low-flow ischemia prevented ischemic contracture (left ventricular
      end-diastolic pressure [LVEDP], 12 +/- 3 compared with 48 +/- 14 mm Hg in 20
      control hearts; P < .001), reduced membrane damage (creatine kinase [CK] release,
      -54% compared with control hearts; P < .05), and enhanced functional recovery
      during reperfusion (left ventricular developed pressure [LVDP], 86 +/- 10% of
      baseline compared with 56 +/- 23% in control hearts; P < .01). These observations
      were not related to increased intracavitary pressure and its effects on flow
      distribution, since venting the left ventricle in additional hearts did not
      result in improved function during reperfusion. Although it would be tempting to
      conclude that BDM protected ischemic myocardium by preventing ischemic
      contracture, administration of BDM was also associated with reduced depletion of
      ATP during ischemia, perhaps related to diminished energy demand. To distinguish
      between the relative importance of inhibiting contracture from provision of
      adequate energy, the period of ischemia was extended to 120 minutes. BDM still
      prevented ischemic contracture (LVEDP, 10 +/- 6 mm Hg) and preserved ATP stores,
      but it did not prevent membrane damage (CK release, 483 +/- 254 U/g dry weight)
      or contractile failure during reperfusion (LVDP, 68 +/- 7% of baseline). In
      contrast, increasing the rate of anaerobic glycolysis during ischemia by doubling
      glucose and insulin in the presence of BDM markedly decreased membrane damage (CK
      release, 114 +/- 72 U/g dry weight; P < .05) and contractile failure during
      reperfusion (LVDP, 88 +/- 7% recovery of baseline; P < .01). These results
      suggest that insufficient energy production is primarily responsible for
      myocardial ischemic damage, whereas mechanical effects of ischemic contracture
      appear to play only a minor role.

PMID- 8156630
TI  - Lactate transport in mammalian ventricle. General properties and relation to K+
      fluxes.
AB  - Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis
      has been implicated as a potential cause of the marked cellular K+ loss
      contributing to lethal cardiac arrhythmias in ischemic heart and to impaired
      function of fatigued skeletal muscle. To examine the mechanisms of
      transsarcolemmal L-lactate movement in the heart, isolated guinea pig ventricular
      myocytes were loaded with the fluorescent H+ or K+ indicators, carboxy SNARF-1 or
      PBFI, respectively, under whole-cell patch-clamp conditions. With H+ as the only
      permeable monovalent cation, a rapid increase in extracellular L-lactate
      concentration ([L-]o) from 0 to 30 mmol/L at constant pHo (7.35) caused an
      intracellular acidification averaging 0.18 +/- 0.02 pH units in 60 seconds (n =
      7), reflecting L-lactate influx in association with H+ influx (or OH- efflux).
      Under voltage-clamp conditions, no significant electrogenic current was
      associated with H(+)-coupled L-lactate influx, and membrane potential (-75 to +75
      mV) had no effect on the degree of acidification produced by 30 mmol/L [L-]o,
      indicating that L-lactate influx was predominantly nonelectrogenic. Acidification
      in response to increased [L-]o was saturable (Km, approximately 5 mmol/L),
      partially stereospecific for L-lactate over D-lactate, and inhibited by 55 +/- 7%
      and 82 +/- 7% by the monocarboxylate carrier inhibitors alpha-cyano-4
      hydroxycinnamate and mersalyl acid, respectively, consistent with a carrier
      mediated transport mechanism. Extracellular K+ inhibited H(+)-coupled L-lactate
      influx by 36 +/- 2%, suggesting that K+ either inhibited or substituted for H+ in
      cotransport with L-lactate. However, in myocytes loaded with PBFI, no significant
      increase in [K+]i was detected during exposure to 30 mmol/L [L-]o, suggesting
      that only a minor component, if any, of L-lactate influx was cotransported or
      codiffused with K+.

PMID- 8156631
TI  - Restricted distribution of connexin40, a gap junctional protein, in mammalian
      heart.
AB  - Connexin40 (Cx40) is a member of the connexin family of gap junction proteins.
      Its mRNA, abundant in lung, is also present in mammalian heart, although in lower
      amount. Rabbit antipeptide antibodies directed to the COOH terminus (residues 335
      to 356) of rat Cx40 were characterized to investigate the distribution of Cx40 in
      rat and guinea pig cardiac tissues. The affinity-purified antibodies detect
      specifically a major protein (M(r), 40,000) in immunoblots of total extracts from
      rat lung and rat and guinea pig heart. In sections of guinea pig atrial tissue
      treated for immunofluorescence, a strong labeling associated with myocytes was
      seen with a distribution consistent with that of intercalated disks. The results
      of immunoelectron microscopy carried out with guinea pig atrial tissue showed
      that epitopes recognized by these antibodies were exclusively associated with gap
      junctions. These results, added to those of control experiments, demonstrate that
      antibodies 335-356 are specific for Cx40. Double-labeling experiments carried out
      with lung sections using anti-factor VIII and anti-Cx40 antibodies suggest that
      Cx40 is expressed in blood vessel endothelial cells. In guinea pig and rat heart
      sections, investigated using both immunofluorescence and immunoperoxidase
      techniques, a signal was also found to be associated with vascular walls. In
      guinea pig heart, only atrial myocytes are Cx40-positive. No labeling was
      detected in ventricular myocytes, including those of the His bundle and the
      bundle branches, which otherwise do express connexin43 (Cx43). In rat heart Cx40
      expressing myocytes are localized in branches, and the Purkinje fibers. Cx43 is
      not detected either in the His bundle or in the proximal parts of the bundle
      branches, and consequently, Cx40 is the first connexin demonstrated in this
      region of the rat conduction system. Cx40 was not detected in the working
      ventricular myocytes. Double-labeling experiments carried out with hen anti-Cx43
      antibodies and rabbit anti-Cx40 antibodies demonstrated that, in tissues
      expressing both Cx43 and Cx40, these two connexins were localized in the same
      immunoreactive sites. A few sites, however, appear to contain only one or the
      other of these two connexins.

PMID- 8156632
TI  - Endothelial expression of thrombomodulin is reversibly regulated by fluid shear
      stress.
AB  - The vascular endothelium, by virtue of its position at the interface between
      blood and the vessel wall, is known to play a critical role in the control of
      thrombosis and fibrinolysis. Thrombomodulin (TM) is a surface receptor that binds
      thrombin and is a potent activator of the protein C anticoagulant pathway.
      Although TM expression is known to be regulated by various cytokines, little is
      known about its response to ever-present biomechanical stimuli. We have explored
      the role of fluid shear stress, imparted on the luminal surface of the
      endothelial cell as a result of blood flow, on the expression of TM mRNA and
      protein in both bovine aortic endothelial (BAE) and bovine smooth muscle (BSM)
      cells in an in vitro system. We report in the present study that TM expression is
      regulated by flow. Subjecting BAE cells to fluid shear stress in the
      physiological range of magnitude of 15 (moderate shear stress) and 36 (elevated
      shear stress) dynes/cm2 resulted in a mild transient increase followed by a
      significant decrease in TM mRNA to 37% and 16% of its resting level,
      respectively, by 9 hours after the onset of flow. In contrast, shear stress at
      the low magnitude of 4 dynes/cm2 did not affect TM mRNA levels. The sensitivity
      of TM mRNA expression by flow was found to be specific to endothelium, since it
      was not observed in BSM cells exposed to steady laminar shear stress of 15
      dynes/cm2. Furthermore, unlike BAE cells, BSM cells did not exhibit altered cell
      shape nor align in the direction of flow after 24 hours of shear stress at 15
      dynes/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156633
TI  - Hypoxia inhibits myogenic reactivity of renal afferent arterioles by activating
      ATP-sensitive K+ channels.
AB  - Recent findings implicate K+ channels as important modulators of myogenic tone
      and possible mediators of the vasodilatory effects of hypoxia. In the present
      report, we examined the effects of hypoxia on myogenic vasoconstriction of renal
      afferent arterioles. Using the in vitro perfused hydronephrotic rat kidney model,
      we observed precisely graded decreases in arteriolar diameter when renal
      perfusion pressure was increased. Normal myogenic reactivity was observed over
      PO2 levels of 150 to 80 mm Hg. Reducing PO2 to 60, 40, and 30 mm Hg resulted in a
      significant progressive inhibition of myogenic reactivity. At approximately 20 mm
      Hg, myogenic vasoconstriction was essentially abolished, whereas the
      vasoconstriction induced by 30 mmol/L KCl was unaffected. The addition of 1.0
      mumol/L glibenclamide completely restored myogenic vasoconstriction during
      hypoxia. In contrast, 1.0 mmol/L tetraethylammonium did not alter the effects of
      hypoxia. To investigate the relation between hypoxia-induced vasodilation and
      smooth muscle oxidative phosphorylation, we monitored changes in arteriolar
      levels of reduced NADH during exposure to hypoxia. Arterioles preconstricted by
      elevated pressure were optically isolated for simultaneous monitoring of vessel
      diameter and NADH fluorescence (360-nm excitation, 450-nm emission). Reducing
      perfusate PO2 from 150 to 20 mm Hg resulted in progressive loss of myogenic tone
      with no change in arteriolar NADH. These findings indicate that lowering PO2
      within a physiological range attenuates myogenic reactivity of the renal afferent
      arteriole by causing the activation of ATP-sensitive K+ channels.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156634
TI  - Reoxygenation-induced relaxation of coronary arteries. A novel endothelium
      dependent mechanism.
AB  - Coronary artery contractility is well known to be modulated by oxygen partial
      pressure. Both smooth muscle and the endothelium contribute to coronary artery
      oxygen sensitivity. Mechanisms underlying endothelium-dependent effects of oxygen
      include the sensitivity of the nitric oxide/endothelium-derived relaxing factor
      (EDRF), hydrogen peroxide, and eicosanoid pathways. In the present study, we
      characterize a novel endothelium-dependent component of porcine coronary artery
      oxygen sensitivity that is independent of these known pathways. Porcine coronary
      arteries were stimulated with either KCl or U46619. Hypoxia elicited a transient
      increase in force that was much greater in endothelium-intact arteries. This
      effect was abolished by nitric oxide/EDRF pathway inhibitors NG-monomethyl-L
      arginine and N-nitro-L-arginine. In the steady state, hypoxia reduced isometric
      force to a similar degree in both intact and denuded arteries. Reoxygenation
      elicited a rapid and transient relaxation only in intact arteries. In contrast,
      this endothelium-dependent relaxation was not inhibited by nitric oxide/EDRF
      pathway inhibitors nor inhibitors of other potential oxygen-sensitive pathways,
      such as indomethacin, aminotriazole, superoxide dismutase, catalase, propranolol,
      or ouabain. The reoxygenation relaxation was, however, sensitive to very low
      levels of oxygen and was inhibited by cyanide and rotenone, suggesting an
      involvement of mitochondrial metabolism. Interestingly, the relaxation response
      to reoxygenation, similar to that for substance P, could be restored in denuded
      arteries by coupling with an endothelium-intact donor artery. This "sandwich"
      experiment suggests that the endothelium dependence is mediated by a
      transmissible factor. Our results indicate that a novel class of endothelium
      dependent factors may contribute to coronary artery responses to changes in
      oxygen partial pressure.

PMID- 8156635
TI  - Mapping the conversion of atrial flutter to atrial fibrillation and atrial
      fibrillation to atrial flutter. Insights into mechanisms.
AB  - It is not generally believed that there is a relation between atrial flutter,
      thought to be due to a single reentrant circuit, and atrial fibrillation, thought
      to be due to simultaneously circulating multiple-reentrant wave fronts. However,
      there are many reasons to suggest that these rhythms are more closely related
      than previously thought. To test the hypothesis that the length of an area of
      functional block in the right atrial free wall is critical to the conversion of
      atrial flutter to atrial fibrillation and of atrial fibrillation to atrial
      flutter, we studied spontaneous and ATP-induced conversion of stable atrial
      flutter to sustained atrial fibrillation and spontaneous conversion of sustained
      atrial fibrillation to stable atrial flutter. We studied 13 episodes of the
      conversion of stable atrial flutter to sustained atrial fibrillation and
      sustained atrial fibrillation to stable atrial flutter in seven dogs with sterile
      pericarditis. Six episodes were spontaneous and seven were ATP related. All
      episodes were studied by using a multisite mapping system to record 190 unipolar
      electrograms (converted in the software to 95 bipolar electrograms) from the
      right atrial free wall along with ECG lead II. Atrial flutter induction was
      attempted by atrial stimulation (S1S2 or S1S2S3) or by rapid atrial pacing for >
      or = 20 beats from selected sites at selected rates. For both the spontaneous and
      the ATP-related episodes, stable atrial flutter was defined as any episode of >
      or = 5 minutes, and sustained atrial fibrillation was any episode of > or = 1
      minute. During all the episodes of stable atrial flutter, a line of functional
      block with a mean length of 24 +/- 4 mm was localized on the right atrial free
      wall. When the previously stable line of functional block decreased to a mean of
      16 +/- 3 mm (P < .05), either spontaneously or after ATP administration (40 mg
      i.v.), the new line of functional block was not long enough to maintain stable
      atrial flutter, and conversion to atrial fibrillation resulted. This shortened
      line of functional block continued to change and migrate over the right atrial
      free wall throughout sustained atrial fibrillation. These observations were
      similar for both spontaneous and ATP-induced conversions. When sustained atrial
      fibrillation evolved to stable atrial flutter, there was reformation of a long
      line of functional block, long enough (> or = prior length) to create a stable
      reentrant circuit, which then captured the right atrial free wall and
      subsequently both atria.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8156636
TI  - Activation of cardiac vagal afferents by oxygen-derived free radicals in rats.
AB  - Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal
      afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold
      Jarisch effect). We postulate that oxygen-derived free radicals, which are well
      known to be produced during prolonged ischemia and reperfusion, contribute to
      this excitation. Hydroxyl radicals derived from hydrogen peroxide (H2O2) activate
      abdominal sympathetic afferents and produce reflex excitation of the
      cardiovascular system. However, it is not known whether inhibitory vagal cardiac
      afferents are activated by oxygen-derived free radicals. We recorded activity
      from 52 single vagal afferent fibers in 29 rats; the endings of these fibers were
      located in the walls of all four chambers of the heart. Thirty-three (63%) of
      these fibers were classified as chemosensitive C-fiber endings because of their
      irregular discharge under resting conditions, their activation in response to the
      topical application of capsaicin (1 to 10 micrograms) to the surface of the heart
      encompassing the receptive field, and their conduction velocities. Fourteen (27%)
      of the remaining fibers were found to be mechanoreceptors. Topical application of
      H2O2 to the heart activated 50% of the chemosensitive endings and did not
      directly affect cardiac mechanoreceptors. Activity increased by 498% at a dose of
      3 mumol (P < .001). This effect was reproducible and dose dependent and was not
      due to [H+]. Topical application of xanthine/xanthine oxidase (20 mmol/0.03 mU)
      activated 8 of the 12 chemosensitive fibers tested and had no direct effect on
      mechanosensitive fibers. Activity increased by 287% (P < .001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156637
TI  - Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins
      versus oxygen-derived free radicals.
AB  - Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal nerve
      endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect).
      We postulate that oxygen-derived free radicals, which are known to be produced
      during prolonged ischemia and reperfusion, contribute to this afferent
      excitation. We recorded activity from 47 chemosensitive vagal afferent fibers in
      31 rats; the endings of these fibers were located in the left ventricle.
      Chemosensitive endings were identified with topical applications of capsaicin (10
      micrograms) to the surface of the heart. Reactivity of the endings to oxygen
      derived free radicals was assessed by topical application of H2O2 (3 to 9 mumol).
      Activity of the vagal fibers was recorded during 30 minutes of occlusion of the
      left anterior descending coronary artery (LAD) and 10 minutes of subsequent
      reperfusion. The activity of chemosensitive endings within the ischemic zone
      increased in the first 2 minutes of LAD occlusion from 2.2 +/- 0.4 to 4.3 +/- 0.9
      impulses per second (107 +/- 30% increase, P < .05). This increased activity
      waned after 3 to 5 minutes of occlusion. Endings outside the ischemic zone did
      not increase, their activity at the beginning of ischemia. Reperfusion caused a
      rapid elevation of activity only in chemosensitive fibers whose endings were
      found to respond to topical H2O2. The reperfusion-sensitive endings were located
      both within and outside the ischemic zone of the left ventricle. Indomethacin (5
      mg/kg i.v., 20 minutes before occlusion) effectively prevented activation of
      chemosensitive afferent endings at the beginning of LAD occlusion regardless of
      their sensitivity to H2O2 but had no effect on the activation at reperfusion.

PMID- 8156638
TI  - In vivo characterization of vasodilating muscarinic-receptor subtypes in humans.
AB  - The role of muscarinic (M)-receptor subtypes in the regulation of vascular tone
      has not yet been defined in humans. To analyze the role of M-receptor subtypes in
      the forearm resistance vasculature of normotensive volunteers (n = 20), we
      infused acetylcholine (ACh) and methacholine (MCh) in the presence of saline and
      the antagonists atropine (nonselective), pirenzepine (M1 selective), and AF-DX
      116 (M2 selective), using automated R-wave-triggered venous occlusion
      plethysmography. Schild analysis was applied by calculating plasma concentrations
      of the infused compounds and determining EC50 values. ACh and MCh both caused
      dose-dependent vasodilation, with EC50 values of 537 and 52 nmol/L, respectively.
      The apparent 10-fold higher potency of MCh compared with ACh may be explained by
      rapid degradation of ACh in plasma. The concentration-response curve of MCh was
      shifted to the right by atropine, pirenzepine, and AF-DX 116, with apparent pA2
      values of 8.03 +/- 0.03, 6.71 +/- 0.08, and 5.32 +/- 0.05, respectively, and
      slopes not different from unity. The present technique enabled us to perform M
      receptor characterization by Schild analysis in humans. The affinity constants
      and rank order of potency--atropine > pirenzepine > AF-DX 116-suggest that
      cholinergic vasodilation in this vascular bed is predominantly mediated by the M3
      receptor subtype. The EC50 value of MCh and the pA2 values of pirenzepine and AF
      DX 116 are comparable to values reported for in vitro experiments.

PMID- 8156639
TI  - Myocardial ischemic contracture. Metabolites affect rigor tension development and
      stiffness.
AB  - Myocardial ischemia is characterized by a decrease in phosphocreatine (PCr) and
      Mg(2+)-ATP contents as well as an accumulation of myosin ATPase reaction products
      (inorganic phosphate [P(i)], protons, and Mg(2+)-ADP). The possibility that these
      metabolites play a role in rigor tension development was checked in rat
      ventricular Triton X-100-skinned fibers. Rigor tension was induced by stepwise
      decreasing [Mg(2+)-ATP] in the presence or in the absence of 12 mmol/L PCr. To
      mimic the diastolic ionic environment of the myofibrils, [free Ca2+] was set at
      100 nmol/L (pCa 7); [free Mg2+], at 1 mmol/L; and ionic strength, at 160 mmol/L.
      In control conditions (pH 7.1, with no added P(i) or Mg(2+)-ADP), the pMg(2+)-ATP
      for half-maximal rigor tension (pMg(2+)-ATP50) was 5.07 +/- 0.03 in the presence
      of PCr. After withdrawal of PCr, the pMg2+)-ATP50 value was shifted toward higher
      Mg(2+)-ATP values (3.57 +/- 0.03). Addition of 20 mmol/L P(i) shifted the pMg(2+)
      ATP50 to 3.71 +/- 0.04 (P < .05) in the absence of PCr and in the opposite
      direction to 4.98 +/- 0.02 (P < .01) in the presence of PCr. Acidic pH (6.6)
      strongly increased pMg(2+)-ATP50 in both the absence (3.90 +/- 0.03, P < .001)
      and presence (5.44 +/- 0.02, P < .001) of PCr. Conversely, Mg(2+)-ADP (250
      mumol/L) decreased pMg(2+)-ATP50 to 3.26 +/- 0.06 (P < .001) in the absence of
      PCr; at pMg(2+)-ATP 4, no rigor tension was observed until PCr concentration was
      decreased to < 2 mmol/L. At acidic pH, maximal rigor tension was lower by 29%
      compared with control conditions, whereas in the presence of Mg(2+)-ADP, maximal
      rigor tension developed to 143% of the control value; P(i) had no effect. The
      tension-to-stiffness (measured by the quick length-change technique) ratio was
      lower in rigor (no PCr and pMg(2+)-ATP 6) than during Ca2+ activation in the
      presence of both PCr and ATP. Compared with control rigor conditions, this
      parameter was unchanged by Mg(2+)-ADP and decreased by acidic pH, suggesting a
      proton-induced decrease in the amount of force per crossbridge. In addition to
      their known effects on active tension, Mg(2+)-ADP and protons affect rigor
      tension and influence ischemic contracture development. It is concluded that
      ischemic contracture and increased myocardial stiffness may be mediated by a
      decreased PCr and local Mg(2+)-ADP accumulation. This emphasizes the importance
      of myofibrillar creatine kinase activity in preventing ischemic contracture.

PMID- 8156640
TI  - Distinct receptors and signaling pathways in alpha-thrombin- and thrombin
      receptor peptide-induced vascular contractions.
AB  - The vasoactive mechanisms of the serine protease alpha-thrombin were examined in
      isolated coronary arteries from dogs. In resting coronary arteries with
      endothelium, alpha-thrombin caused concentration-dependent contractions that were
      characterized by an initial transient relaxation followed by slowly developing
      sustained contractions. The vascular actions of alpha-thrombin were mimicked by
      the thrombin receptor-activating peptide (TRAP) SFLLRNP, a synthetic peptide
      based on the cleaved terminus of the thrombin receptor domain. Treatment of the
      arteries with N omega-nitro-L-arginine or removal of endothelium abolished the
      transient relaxations and enhanced the contractions, indicating that the
      transient relaxations were mediated by the concurrent release of endothelium
      derived nitric oxide. alpha-Thrombin that had been catalytically inactivated with
      the irreversible inhibitor by use of D-Phe-Pro-Arg-chloromethyl ketone did not
      cause contractions, indicating the requirement of proteolytic cleavage by alpha
      thrombin to induce contractions. In contrast to TRAP, alpha-thrombin-induced
      contractions were blocked by hirudin (a specific thrombin inhibitor), nifedipine
      and diltiazem (Ca2+ channel blockers), or staurosporine and calphostin C (protein
      kinase C inhibitors). Unlike alpha-thrombin, which undergoes homologous
      desensitization, TRAP failed to cause desensitization to subsequent stimulation
      by alpha-thrombin or TRAP. These observations support the hypothesis that
      vasoactive actions of alpha-thrombin are mediated by a mechanism that involves
      cleavage at the active site to expose a new NH2 terminus that activates the
      thrombin receptor. Further, the dissociation between alpha-thrombin and the
      synthetic receptor peptide in signal transduction and dissimilar desensitizing
      properties suggest the existence of distinct thrombin receptor subtypes and/or
      signaling events in vascular smooth muscle.

PMID- 8156641
TI  - Measurement of renal perfusion and blood flow with fast computed tomography.
AB  - Fast computed tomography (CT) is one of the few methods available to measure
      cortical and medullary renal blood flow (RBF) directly. Because these
      measurements are complicated by passage of the contrast medium into extravascular
      compartments, we used the residual opacity following the vascular blush as an
      index to account for extravascular iohexol. Kidneys of anesthetized dogs were
      examined in situ by fast CT following intra-aortic injections of iohexol.
      Perfusion was analyzed during a control period and three subsequent periods in
      which RBF was reduced by 10%, 30%, and 50%. Cortical microvascular distribution
      volume changed from 19.7 +/- 2.8% to 19.8 +/- 1.7%, 15.3 +/- 1.2%, and 9.9 +/-
      1.7%, respectively, without significant alterations in cortical mean transit
      time. Microvascular distribution volume was divided by mean transit time to
      determine tissue perfusion. Cortical perfusion changed from 3.8 +/- 0.7 to 3.9 +/
      0.6, 3.1 +/- 0.5, and 2.2 +/- 0.5 mL.min-1.mL tissue-1. Total cortical blood
      flow (cortical perfusion multiplied by cortical volume) decreased from 164 +/- 32
      to 159 +/- 31, 117 +/- 20, and 86 +/- 22 mL/min, respectively. Medullary
      microvascular distribution volume, mean transit time, perfusion, and total blood
      flow remained unchanged. Fast CT-determined total RBFs (cortex plus medulla) were
      similar to simultaneous electromagnetic flow measurements. These results indicate
      that renal regional perfusion is more dependent on the microvascular distribution
      volume than mean transit time and that variations in renal tissue perfusion with
      reduction of RBF are more apparent in the cortex than in the medulla.

PMID- 8156642
TI  - Intracellular calcium transient of working human myocardium of seven patients
      transplanted for congestive heart failure.
AB  - The afterload dependence of the intracellular calcium transient in isolated
      working human myocardium was analyzed in both donor and recipient hearts of seven
      patients undergoing transplantation because of dilated cardiomyopathy. The
      intracellular calcium transient (recorded by the fura 2 ratio method), force
      development, and muscle shortening were simultaneously recorded in small (0.6 x
      4.0-mm) electrically driven (60 beats per minute) trabeculas contracting at
      constant preload against varying afterloads. When the fibers contracted under
      isometric conditions, the intracellular calcium transients of normal and failing
      myocardium were similar. However, in dilated cardiomyopathy, stepwise afterload
      reduction and the concomitant increase in shortening amplitudes were associated
      with extraordinary alterations in the shape of the calcium transients; the
      amplitude rose, the time to peak was delayed, and at minimal afterloads, a long
      lasting plateau was observed, and the diastolic decay was retarded. The calcium
      time integral during shortening against passive resting force was 124 +/- 5% of
      the isometric control in normal myocardium and 172 +/- 12% in end-stage heart
      failure (P < .0001). We conclude that adequate interpretation of intracellular
      calcium transients requires simultaneous recordings of force and shortening. The
      extraordinary afterload dependence of the calcium transient in end-stage heart
      failure may be attributed to increased dissociation of calcium from the
      contractile proteins, a reduced calcium reuptake rate of the sarcoplasmic
      reticulum, or an increased calcium inflow due to altered permeabilities of the
      calcium channels during shortening. A potential role of mechanosensitive calcium
      channels has to be considered.

PMID- 8156643
TI  - The failing human heart is unable to use the Frank-Starling mechanism.
AB  - There is evidence that the failing human left ventricle in vivo subjected to
      additional preload is unable to use the Frank-Starling mechanism. The present
      study compared the force-tension relation in human nonfailing and terminally
      failing (heart transplants required because of dilated cardiomyopathy)
      myocardium. Isometric force of contraction of electrically driven left
      ventricular papillary muscle strips was studied under various preload conditions
      (2 to 20 mN). To investigate the influence of inotropic stimulation, the force
      tension relation was studied in the presence of the cardiac glycoside ouabain. In
      skinned-fiber preparations of the left ventricle, developed tension was measured
      after stretching the preparations to 150% of the resting length. To evaluate the
      length-dependent activation of cardiac myofibrils by Ca2+ in failing and
      nonfailing myocardium, the tension-Ca2+ relations were also measured. After an
      increase of preload, the force of contraction gradually increased in nonfailing
      myocardium but was unchanged in failing myocardium. There were no differences in
      resting tension, muscle length, or cross-sectional area of the muscles between
      both groups. Pretreatment with ouabain (0.02 mumol/L) restored the force-tension
      relation in failing myocardium and preserved the force-tension relation in
      nonfailing tissue. In skinned-fiber preparations of the same hearts, developed
      tension increased significantly after stretching only in preparations from
      nonfailing but not from failing myocardium. The Ca2+ sensitivity of skinned
      fibers was significantly higher in failing myocardium (EC50, 1.0; 95% confidence
      limit, 0.88 to 1.21 mumol/L) compared with nonfailing myocardium (EC50, 1.7; 95%
      confidence limit, 1.55 to 1.86 mumol/L). After increasing the fiber length by
      stretching, a significant increase in the sensitivity of the myofibrils to Ca2+
      was observed in nonfailing but not in failing myocardium. These experiments
      provide evidence for an impaired force-tension relation in failing human
      myocardium. On the subcellular level, this phenomenon might be explained by a
      failure of the myofibrils to increase the Ca2+ sensitivity after an increase of
      the sarcomere length.

PMID- 8156644
TI  - 8-bromo-cGMP reduces the myofilament response to Ca2+ in intact cardiac myocytes.
AB  - The role of cGMP in myocardial contraction is not established. Recent reports
      suggest that nitric oxide, released by endothelial cells or within myocytes,
      modifies myocardial contraction by raising cGMP. We studied the effects of 8
      bromo-cGMP (8bcGMP, 50 mumol/L) on contraction (cell shortening) and simultaneous
      intracellular Ca2+ transients (indo 1 fluorescence ratio) in intact adult rat
      ventricular myocytes (0.5 Hz and 25 degrees C) 8bcGMP reduced myocyte twitch
      amplitude and time to peak shortening (-19.6 +/- 4.2% and -17.6 +/- 1.3%,
      respectively) and increased steady-state diastolic cell length (+0.6 +/- 0.1
      microns, mean +/- SEM, n = 8; all P < .05) but had no effect on shortening
      velocity, systolic or diastolic fluorescence ratio, or time to peak fluorescence
      ratio (all P = NS). In 7 of 13 myocytes, this negative inotropic effect was
      preceded by a transient positive inotropic effect, with small increases in twitch
      amplitude, shortening velocity, and cytosolic Ca2+ transient. Analysis of 8bcGMP
      effects on both the dynamic and steady-state relation between cell shortening and
      intracellular Ca2+ (during twitch contraction and tetanic contraction,
      respectively) indicated reduction in the myofilament response to Ca2+ in all
      cases. These 8bcGMP effects were inhibited by KT5823 (1 mumol/L), an inhibitor of
      cGMP-dependent protein kinase, or by the presence of isoproterenol (3 nmol/L).
      8bcGMP had no effect on cytosolic pH in cells (n = 4) loaded with the fluorescent
      probe carboxyseminaphthorhodafluor-1. These data indicate that cGMP may modulate
      myocardial relaxation and diastolic tone by reducing the relative myofilament
      response to Ca2+, probably via cGMP-dependent protein kinase.

PMID- 8156645
TI  - Modulation of Ca2+ release in cultured neonatal rat cardiac myocytes. Insight
      from subcellular release patterns revealed by confocal microscopy.
AB  - It is well established that in heart muscle the influx of Ca2+ through Ca2+
      channels during the action potential is the main trigger for Ca2+ release from
      the sarcoplasmic reticulum (SR), but intact cardiac tissue and single myocytes
      are also known to exhibit spontaneous Ca2+ release from the SR under a variety of
      circumstances. Although conditions favoring spontaneous activity have been
      examined extensively, mechanisms modulating or regulating spontaneous as well as
      triggered Ca2+ release are still largely unknown. Using the high spatial and
      temporal resolution of laser-scanning confocal microscopy, we investigated
      subcellular aspects of spontaneous and triggered Ca2+ release in isolated rat
      neonatal myocytes loaded with the Ca(2+)-sensitive fluorescent dye fluo 3. Three
      distinct patterns of spontaneous Ca2+ release were identified: (1) a homogeneous
      Ca2+ release, presumably corresponding to Ca2+ release during a spontaneous
      action potential, (2) a focal or spatially restricted Ca2+ release with no or
      only limited subcellular propagation, and (3) a Ca2+ release propagating as a
      wave throughout the entire cell. Pharmacologic tools that interfere with the SR
      revealed that all release types were critically dependent on the Ca2+ release and
      uptake function of the SR. From our results we conclude that the probability,
      extent, and pattern of Ca2+ release are modulated on the subcellular level. The
      observed spectrum of release patterns can be explained by a space- and time
      dependent variability in the positive feedback of the Ca(2+)-induced Ca(2+)
      release mechanism within an individual myocyte. Presumably, this variability
      depends on the existence of subcellular functional elements of the SR. The actual
      degree of positive feedback may be modulated locally by the Ca(2+)-loading state
      of each SR element.

PMID- 8156646
TI  - Contractile arrest increases sarcoplasmic reticulum calcium uptake and SERCA2
      gene expression in cultured neonatal rat heart cells.
AB  - We developed protocols with intact cultured neonatal rat myocytes to directly
      evaluate the function of the sarcoplasmic reticulum (SR) Ca-ATPase (or SERCA2),
      Na-Ca exchange (Na-CaX), and slow Ca transport systems (mitochondria and
      sarcolemmal Ca-ATPase). Spontaneously beating control cells were compared with
      cells cultured for 2 days in the presence of verapamil (verapamil-arrested cells,
      VA). Intracellular calcium (Cai) transients were measured by use of indo-1 during
      (1) spontaneous twitches, (2) contractures induced by rapid application of
      caffeine (CafC, with and without Nao), and (3) twitches induced by brief
      depolarizations with high [K]o solution (K-twitches). We also measured mRNA
      levels for the SR Ca-ATPase and Na-CaX in the same experimental preparations. The
      t1/2 for [Ca]i decline when both the SR Ca uptake and Na-CaX were prevented was
      the same for control and VA cells (approximately 20 seconds), indicating
      unaltered slow Ca transport systems. Similarly, there was no significant
      difference in the t1/2 of CafC when Na-CaX was the main mechanism responsible for
      [Ca]i decline (t1/2 approximately 1.5 seconds), indicating unaltered Na-CaX.
      Conversely, we found nearly a twofold increase in the rate of [Ca]i decline
      during K-twitches (control t1/2, 0.84 +/- 0.05 seconds; VA t1/2, 0.48 +/- 0.06
      second; P < .001), indicating an increase in SR Ca-pumping activity in VA cells.
      This was also reflected by a 56% increase in the peak [Ca]i reached during CafC
      used to assess maximal SR Ca content (427 +/- 49 nmol/L in control versus 665 +/-
      75 nmol/L in VA cells).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156647
TI  - Conscious rabbits become tolerant to multiple episodes of ischemic
      preconditioning.
AB  - Although ischemic preconditioning protects myocardium from infarction in isolated
      hearts and in anesthetized open-chest animals, its effects have not been examined
      in unanesthetized animals. Furthermore, it is unknown whether animals become
      tolerant to multiple episodes of ischemic preconditioning. Rabbits were
      chronically instrumented with a balloon occluder around a major branch of the
      left coronary artery for reversible coronary occlusion, a left atrial catheter
      for radioactive microsphere injections, ECG electrodes for monitoring of
      myocardial ischemia, and, in some cases, a carotid artery catheter for pressure
      measurements and timed withdrawal of reference arterial blood samples. Eight
      control rabbits underwent a 30-minute coronary occlusion and then 180 minutes of
      reperfusion. Five of the eight rabbits developed ventricular tachycardia or
      fibrillation during ischemia, and infarct size averaged 37.7 +/- 2.6% of the risk
      area. Eight rabbits experienced a 5-minute coronary occlusion and 10 minutes of
      reperfusion before the 30-minute occlusion. In these preconditioned animals,
      potentially fatal arrhythmias during ischemia were significantly reduced (one of
      eight, P < .05), and infarct size was much smaller (5.6 +/- 1.1%, P < .0001). The
      difference could not be explained by hemodynamics or collateral blood flow, which
      were nearly identical in the two groups. But when the 30-minute coronary
      occlusion was preceded by 40 to 65 five-minute occlusions during a 3- to 4-day
      period in seven animals, protection was markedly attenuated. Potentially lethal
      arrhythmias were very common, and infarct size averaged 26.5 +/- 2.9%,
      substantially larger than in rabbits with only one preconditioning occlusion (P <
      .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156648
TI  - Plasma renin activity during hypotensive responses to electrical stimulation
      carotid sinus nerves in conscious dogs.
AB  - 1. The interaction of electrical stimulation of the carotid sinus nerves (carotid
      sinus nerve stimulation, CSNS) with mechanisms of renin release was studied in
      conscious and unrestrained resting beagle dogs receiving a standardized diet
      (sodium intake, 4.5 mmol/kg bodyweight (bw); water intake, 91 mL/kg bw). 2. By
      CSNS, mean arterial blood pressure (MAP) was lowered for periods of 20 min to
      levels between 101 +/- 4 and 56 +/- 5 mmHg. 3. In another group of conscious
      dogs, renal perfusion pressure (RPP) was lowered to 95 +/- 4 mmHg for periods of
      20 min by partial suprarenal aortic occlusion in order to assess the influence of
      a reduced RPP on plasma renin activity (PRA) without concomitant CSNS. 4. During
      CSNS, PRA increased markedly (> 100%) only when MAP was reduced below 75 mmHg. 5.
      With aortic constriction and an RPP of 95 mmHg, the increase in PRA was 955%,
      which is more than three-fold higher than the increase in PRA during CSNS at MAP
      levels < 65 mmHg (314%). 6. The observed responses indirectly support the
      hypothesis that basal activity in efferent renal nerve discharge is present even
      at rest and can be inhibited by CSNS, and furthermore suggests that CSNS
      attenuated the pressure-dependent renin release.

PMID- 8156649
TI  - The increase of femoral arterial flow by stimulating the dorsal and ventral
      medulla in cats.
AB  - 1. In chloralose-urethane anaesthetized cats, the dorsal cardiovascular reactive
      area (DCRA) in the parvocellular reticular nucleus dorsomedial to the facial
      nucleus, and the ventral cardiovascular reactive area (VCRA) ventromedial to the
      facial nucleus, were stimulated by microinjections of sodium glutamate (100-200
      nmol) or electric current. 2. Stimulation of DCRA, with a long latency of 15-20
      s, elicited a marked increase of blood flow in the contralateral femoral artery
      with little change to moderate increase in systemic arterial blood pressure
      (ABP). In the relatively dorsal portion of DCRA, however, a smaller increase of
      blood flow in the ipsilateral femoral artery was elicited. 3. On the other hand,
      stimulation of VCRA with a short latency (3-5s) evoked an increase of blood flow
      in both femoral arteries which was more prominent on the contralateral side. The
      responses were accompanied with decreases in the blood flow of other vascular
      beds with only a slight increase or minimal change in ABP. 4. The data suggest
      that DCRA and VCRA are both viscerotopically organized to alter the resistance of
      individual vascular beds for redistribution of blood flow.

PMID- 8156650
TI  - The effect of hypertensive episodes and cardiac hypertrophy on the canine cardiac
      baroreflex.
AB  - 1. Left ventricular (LV) hypertrophy has been implicated in the reduction of
      baroreflex sensitivity present in hypertension. The aim of the current study was
      to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model
      which induced left ventricular hypertrophy but no sustained blood pressure
      elevation. 2. Five mongrel dogs were exposed to transient blood pressure
      elevation of between 20 and 30 mmHg, through hindlimb compression using a
      pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting
      blood pressure was not altered by the 6 week hindlimb compression intervention.
      3. Echocardiographically determined LV mass (mean +/- s.e.m.) was 116.0 +/- 7.4 g
      prior to hindlimb compression (baseline) and elevated to 125.4 +/- 8.1 g (P =
      0.003) after 6 weeks of compression. A reduction in the early (E) to late (A)
      transmitral diastolic flow ratio (E/A) from 1.80 +/- 0.06 at baseline to 1.54 +/-
      0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance
      was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the 'steady
      state' drug technique, when blood pressure was normal, showed a trend for
      reduction from 3.85 +/- 0.43 beats/min per mmHg at baseline to 3.10 +/- 0.45
      beats/min per mmHg (P = 0.067) after 6 weeks of compression. This gain reduction
      became significant after beta-adrenoceptor blockade with propranolol (3.13 +/-
      0.55 vs 2.32 +/- 0.25 beats/min per mmHg; P = 0.039). Covariant analysis showed a
      significant inverse correlation between LV mass and maximum gain (r = 0.96; P <
      0.001) during the 6 week compression period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156651
TI  - Renal denervation potentiates the natriuretic and diuretic effects of atrial
      natriuretic peptide in anaesthetized rabbits.
AB  - 1. The role of the renal nerves in modulating the action of atrial natriuretic
      peptide (ANP) in the kidney was studied by comparing the responses to ANP in
      innervated and surgically denervated kidneys in anaesthetized rabbits. 2. A low
      dose of ANP (0.05 microgram/kg per min, i.v.) was used to minimize the
      confounding effects of systemic hypotension. 3. The natriuretic and diuretic
      responses to ANP were significantly greater in denervated kidneys than in kidneys
      with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 +/
      3.11 mumol/min in response to ANP (approximately 55%, P < 0.05) compared to 0.84
      +/- 0.59 mumol/min (approximately 28%, NS) in innervated kidneys. Urine flow
      increased markedly in denervated kidneys by 73.2 +/- 29.9 mumol/min
      (approximately 60%, P < 0.05) but not in innervated kidneys. 4. Fractional sodium
      excretion increased significantly in denervated kidneys in response to ANP
      (median 2.3% to median 3.0%, P < 0.05). 5. Renal blood flow, glomerular
      filtration rate (GFR) and glomerular capillary pressure were unchanged in
      response to ANP in either denervated or innervated kidneys. Pre-glomerular
      vascular resistance fell in denervated kidneys during ANP infusion. 6. The
      natriuresis and diuresis observed in the denervated kidneys, due to an increased
      fractional excretion of sodium without increases in GFR or glomerular capillary
      pressure, is consistent with effects of ANP on tubular reabsorption of sodium. 7.
      Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not
      in innervated kidneys. This indicates that reflex activation of renal nerves may
      antagonize the renal effects of ANP.

PMID- 8156652
TI  - Effects of calcium- and ETA-receptor antagonists on endothelin-induced
      vasoconstriction and levels of endothelin in the human internal mammary artery.
AB  - 1. The effects of the ETA receptor antagonist BQ123 and dihydropyridine calcium
      antagonists on the vasoconstrictor effect of endothelin-1 (ET-1) were studied in
      human isolated internal mammary artery (IMA). The effect of the calcium
      antagonist, nisoldipine, on ET-1 levels has also been examined in cultured IMA
      endothelial cells (IMAEC). 2. The results showed that BQ123 and the calcium
      antagonists nisoldipine, isradipine, nitrendipine and nifedipine fully relaxed
      IMA precontracted with 3 nmol/L ET-1 with the EC50 values of 7.18 +/- 0.09 (-log
      mol/L) for BQ123, and 7.68 +/- 0.07, 7.02 +/- 0.12, 6.96 +/- 0.08 and 6.89 +/-
      0.09 for the calcium antagonists, respectively. 3. Pretreatment of IMA with 10,
      30, 100 and 300 nmol/L nisoldipine significantly depressed the maximal response
      (Max; 88.3 +/- 5.1, 75.2 +/- 4.9, 59.3 +/- 5.6 and 56.2 +/- 4.8% of maximal
      noradrenaline response versus 99.1 +/- 13.2% in control, P < 0.01) of IMA to ET-1
      without a significant change in the EC50 values. 4. Pretreatment of IMA with 300
      nmol/L BQ123 significantly increased both the EC50 (7.97 +/- 0.09 vs 8.36 +/-
      0.08 in the control, P < 0.05) and the Max (138.1 +/- 10.2% vs the control, P <
      0.01) of IMA to ET-1. 5. Incubation of IMAEC with nisoldipine for 7 h resulted in
      a dose-dependent (10(-8)-10(-5) mol/L) reduction up to 93.1% in ET levels in the
      conditioned media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156653
TI  - Effects of anti-emetics on water excretion in humans.
AB  - 1. The anti-emetic drug metoclopramide has been shown to stimulate secretion of
      the antidiuretic hormone arginine vasopressin. Since metoclopramide is used to
      treat nausea, which is another potent stimulus to vasopressin secretion, the aim
      of this study was to determine whether metoclopramide might limit free water
      excretion and so cause hyponatraemia. 2. Metoclopramide 20 mg (0.2-0.3 mg/kg),
      prochlorperazine 12.5 mg (0.1-0.2 mg/kg) and placebo were administered
      intravenously in a double blind randomized crossover way at 2 week intervals and
      the effects on urine flow rate, plasma osmolality, thirst ratings and plasma
      sodium and atrial natriuretic peptide concentrations determined in water-loaded
      (10 mL/kg) healthy young men. 3. There were no differential effects on any
      variable of either drug versus placebo. 4. These results indicate that
      metoclopramide is unlikely to cause any significant water retention in a clinical
      setting or precipitate hyponatraemia.

PMID- 8156654
TI  - Does phosphorylation affect transport of inorganic phosphate?
AB  - 1. This study investigated the effects of fructose and 2-deoxyglucose on the
      uptake and release of phosphate from everted intestinal sacs of mice. 2. Both the
      sugars significantly decreased the release of phosphate without affecting the
      uptake. 3. Succinate and fumarate were able to partially reverse the inhibition
      of phosphate release exerted by fructose but not that exerted by 2-deoxyglucose.
      4. Pre-loading with mannoheptulose, a known inhibitor of hexokinase, improved the
      release of phosphate in the presence of either of these sugars. 5. Adrenaline,
      known to inhibit phosphorylation of 2-deoxyglucose, reduced the inhibition
      exerted by this sugar on phosphate release. 6. These results indicate that the
      inhibition of phosphate release caused by these sugars may be due to the trapping
      of free phosphate during their metabolism in the gut wall.

PMID- 8156655
TI  - Hypothesis: cytotoxic lymphocyte granule serine proteases activate target cell
      endonucleases to trigger apoptosis.
AB  - Upon interaction with target cells, cytotoxic T lymphocytes and natural killer
      cells vectorially secrete highly specialized cytoplasmic granules containing
      perforin and a family of serine proteases (granzymes). This granule exocytosis
      mechanism of cytolysis is of patho-physiological importance, and usually results
      in target cell DNA fragmentation. Neither perforin nor granzymes possess inherent
      nuclease activity, but in combination they can induce target cell apoptosis.
      Perforin forms transmembrane pores in the target cell, thereby enabling granzymes
      to access target cell substrates. The target cell substrates of granzymes are
      unknown, but granzyme A binding and cleavage of the nuclear shuttle protein
      nucleolin in target cells demonstrates that granzymes may act on nuclear
      substrates. Furthermore, the presence of granzyme B and other granzyme activities
      in the nucleus of cytotoxic lymphocytes indicates that granzymes can be
      transported from the cytoplasm to the nucleus. It is hypothesized that perforin
      enables effector granzymes to enter the target cell cytoplasm and following their
      transport into the nucleus, granzymes cleave specific target cell nuclear
      proteins to activate autolytic endonucleases that fragment DNA. In cytotoxic
      effectors, these nuclear substrates are normally protected from granzymes by
      endogenous inhibitors.

PMID- 8156656
TI  - Pharmacological actions of the coenzymes NAD(H) and NADP(H) on the rat
      anococcygeus muscle.
AB  - 1. The pharmacological actions of the oxidized and reduced forms of nicotinamide
      adenosine dinucleotide (NAD, NADH) and nicotinamide-adenosine dinucleotide
      phosphate (NADP, NADPH) were studied on rat isolated anococcygeus muscles. 2. The
      actions of the two nucleotides were different, but there were no apparent
      qualitative differences between the oxidized and reduced forms of each. 3. In
      fully relaxed anococcygeus muscles, NADP(H) produced transient contractions that
      were subject to desensitization, but NAD(H) had no effect. 4. NADP(H) slightly
      enhanced contractions elicited by noradrenergic nerve stimulation. In contrast,
      noradrenergic contractions were inhibited by NAD(H). NADH reduced the stimulation
      induced release of noradrenaline, but enhanced contractions elicited by exogenous
      noradrenaline. 5. In anococcygeus muscles partly contracted with guanethidine,
      NAD(H) produced a further sustained increase in tone; in contrast, NADP(H) mainly
      produced transient relaxations to which there was immediate desensitization. 6.
      Relaxations of anococcygeus muscle elicited by nitrergic nerve stimulation were
      not affected by NAD. In contrast, NADP(H) reduced them. 7. The actions of NAD(H)
      were generally the same as those of adenosine and can be attributed to activation
      of P1-purinoceptors since they were blocked by the selective antagonist 8
      sulphophenyltheophylline. 8. The actions of NADP resembled those of the P2
      purinoceptor agonist ATP to some extent, but there were some differences. As
      suggested by others, NADP may act on a unique receptor.

PMID- 8156657
TI  - Thrombolytic therapy: pre- and post-GISSI-2, ISIS-3, and GUSTO-1.
AB  - At present, data are available from three large-scale randomized trials of
      mortality that directly compared different thrombolytic regimens, namely, GISSI
      2, ISIS-3, and GUSTO-1. These trials randomized over 100,000 patients worldwide.
      When examined individually as well as in aggregate, these trials demonstrate at
      most only small absolute differences between thrombolytic agents both in terms of
      lives saved and major complications, including hemorrhagic stroke. Specifically,
      TPA produces more strokes and cerebral bleeds, but whether or not there is a
      small incremental mortality benefit is not yet clear. All three trials indicate
      that the choice of thrombolytic agent is much less important to ultimate survival
      than is the delay time between onset of symptoms and initiation of treatment.
      Further, any potential differences in efficacy and safety between the available
      thrombolytic agents are unlikely to pertain to the majority of infarct patients
      who present to hospitals more than 4 h after the onset of symptoms. Since all
      three agents appear to be effective when given up to 12 h after the onset of
      symptoms, a clinical strategy must be adopted to increase thrombolytic
      utilization for late arrivers regardless of which agent is chosen. Patients
      excluded from thrombolytic therapy because of age, gender, presence of bundle
      branch block on admitting electrocardiogram, and late arrival in the emergency
      department in fact benefit substantially from thrombolysis as long as
      contraindications to the drug do not exist. Nonetheless, only one-third of U.S.
      patients with acute myocardial infarction receive thrombolytic therapy, compared
      with over two-thirds of patients in the United Kingdom and several other European
      countries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156658
TI  - The role of percutaneous transluminal coronary angioplasty in acute myocardial
      infarction.

PMID- 8156659
TI  - Complications of limb lengthening. A learning curve.
AB  - Major complication rates during limb lengthening were plotted in a consecutive
      series to produce a learning curve. All unwanted events during and after
      treatment were considered complications, and graded as minor, serious, and
      severe. All serious and severe complications were considered major. A novel
      system was used to classify the preoperative severity of each deformity. One
      hundred ten patients had 140 bone segments lengthened between 2.2 cm and 10.5 cm,
      with a mean of 4.4 cm. Three methods were used in lengthening: the Wagner method
      in 22 patients, the DeBastiani method in 34 patients, and the Ilizarov method in
      84 patients. Ninety-eight complications categorized as serious or severe
      occurred, for a total major complication rate of 72%. The percentage of major
      complications began to drop after 30 lengthenings to a current rate of 25%. Major
      complications were frequent in patients with more severe deformities,
      particularly in those whose cases occurred early in the series. Bone healing
      complications were high (72%) in the Wagner segments but were also high (80%) in
      the first ten patients treated with the DeBastiani technique. The first ten
      Ilizarov patients, who were treated later in the series, had a 40% rate of bone
      healing complications. The current rate of major complications is 13% for those
      patients treated with DeBastiani's method and 33% for those patients treated with
      Ilizarov's method. This difference in complication rates appears to relate to the
      severity of the deformity, rather than the device used. There was a significant
      decrease in complications as experience was gained. Directed formal study and
      surgical instruction should help diminish these complications.

PMID- 8156660
TI  - Accuracy of correction of complex lower-extremity deformities by the Ilizarov
      method.
AB  - Gradual mechanical distraction with the Ilizarov external fixator was used on 28
      limbs in 23 patients to correct complex lower-extremity deformities of diverse
      causes. To determine the accuracy of realignment and deformity correction, the
      charts and radiographs were reviewed retrospectively. Preoperative long-standing
      anteroposterior radiographs of the entire lower extremity were compared with
      those obtained at the most recent follow-up visit. The parameters used to assess
      accuracy of correction were joint alignment and joint orientation. Alignment was
      determined by mechanical axis deviation (MAD) and mechanical tibiofemoral angle
      (mTFA). The preoperative MAD averaged 48 mm and the postoperative MAD 8.6 mm. The
      preoperative mTFA averaged 16 degrees and the postoperative mTFA 3 degrees. The
      result of deformity correction from early cases was compared with the result
      obtained from recent cases. Residual MAD averaged 13.2 mm in the early group and
      6.4 mm in the recent group. Residual mTFA averaged 4.7 degrees in the early group
      and 2.2 degrees in the recent group. Gradual correction by dynamic external
      fixation can restore alignment and correct complex deformities with great
      accuracy. These results suggest the accuracy of correction increases with
      surgical experience.

PMID- 8156661
TI  - Skeletal defects. A comparison of bone grafting and bone transport for segmental
      skeletal defects.
AB  - To evaluate two different methods of managing segmental skeletal defects, 15
      patients treated with the open bone graft (Papineau) technique were compared with
      17 patients who had intercalary bone transport (Ilizarov) management. The
      treatment time was identical for both groups: 1.9 months in fixation for each
      centimeter of defect reconstructed. Both techniques shared several fixator
      associated problems such as implant site sepsis and patient discomfort. Each
      method of treatment, however, had its own unique problems. For the bone grafted
      group, limited graft availability, donor site morbidity (three patients), and
      graft fractures (two patients) occurred. For the bone transport group, the main
      problems were failure of the docking site to unite without a supplementary graft
      (seven patients) and joint contractures (seven patients). A new synthesis of both
      techniques is described.

PMID- 8156662
TI  - Segmental tibial defects. Comparing conventional and Ilizarov methodologies.
AB  - Forty-four consecutive patients with segmental debridement defects of the tibia
      had limb-salvage surgery. Twenty-one patients (Group I) were managed using
      methods as described by Ilizarov. Twenty-three patients (Group II) underwent
      conventional treatment with massive cancellous grafts and tissue transfers. Total
      wound consolidation and infection arrest took place after the first treatment in
      71% of the Ilizarov wounds and 74% of the conventionally treated wounds. The
      major complication rates were 33% and 60% for Groups I and II respectively. The
      patient population at highest risk for failure was the compromised host treated
      conventionally (44%). The cost for retreatment and overall success rate (95%)
      were the same for both groups. Ilizarov reconstructions averaged nine fewer hours
      in the operating theater, 23 fewer days in the hospital, five fewer months'
      disability (17 months versus 22 months), and a savings of nearly $30,000 per
      application.

PMID- 8156663
TI  - Temporal and spatial increases in blood flow during distraction osteogenesis.
AB  - Ten adult mongrel dogs underwent left tibial lengthening at the proximal
      metaphysis. They were divided into three groups on the basis of distraction
      period: 14, 28, and 56 days. Quantitative technetium scintigraphy was used to
      measure regional blood flow within the tibiae during distraction, and
      periodically during consolidation, up to 17 weeks after operation. Blood flow was
      measured from regions of interest during the flow phase of the scan and expressed
      as a ratio of lengthened side to control side. At the distraction site, the flow
      increased to nearly ten times control, peaked at two weeks postoperatively, then
      decreased to four to five times the control for the remainder of the distraction
      period. During the consolidation period, significantly increased flow persisted
      at levels of two to three times control. The distal tibiae, away from the
      distraction gap, showed similar amplitude and temporal patterns of increased
      flow. No significant differences were found between the groups tested or when
      compared with similar fracture models. These findings lend credence to Ilizarov's
      hypothesis that distraction osteogenesis may contribute to healing of chronic
      osteomyelitis or hypovascular nonunions at distant sites by inducing a prolonged
      hypervascular state. Whether distraction osteogenesis transforms the normal
      reparative response of bone injury to a regenerative response remains
      conjectural.

PMID- 8156664
TI  - Chronic infected tibial nonunions with bone loss. Conventional techniques versus
      bone transport.
AB  - Twenty-five patients with infected nonunions of the tibia and segmental bone loss
      were treated by one of two methods: resection and bone transport, or conventional
      treatment using less extensive debridement, external fixation, bone grafting, and
      soft-tissue coverage. The two groups were comparable except for gender
      distribution. Each group experienced similar rates of healing; eradication of
      infection; treatment time; final angulation; number of complications; and total
      number of surgical procedures. However, the final limb-length discrepancy was
      significantly less in the bone transport group.

PMID- 8156665
TI  - Force required for bone segment transport in the treatment of large bone defects
      using medullary nail fixation.
AB  - In distraction osteogenesis, different factors influence quality and quantity of
      bone formation. These factors are rigidity of fixation, frequency, and velocity
      of transport; and integrity of periosteum, endosteum, and intramedullary
      vascularization. Little data are available on forces related to distraction
      osteogenesis and limb lengthening, and no data on forces related to bone segment
      transport. This experiment investigates the correlation of the bone regeneration
      process with transport forces. Bone segment transport over an intramedullary nail
      provides an excellent model for measurement of external forces during distraction
      osteogenesis because soft-tissue and muscle resistance is reduced as compared
      with limb lengthening. In an animal experiment (sheep), tibial shaft defects of
      20 mm and 45 mm were treated. External transport forces were measured daily
      during bilateral wire transport of a bone segment over an intramedullary nail.
      Forces increased during transport. Overall transport forces for large defects
      were slightly higher than those for small defects, reaching 350 N by the end of
      transport. For large defects, transport forces leveled off during bone transport
      and rose again at the end. Correspondingly, for large defects, stress relaxation
      within the tissues increased during the third and the sixth week of transport.
      This plateau may be interpreted as a reduction of internal forces within the
      repair tissues at the distraction site, implying a spreading of the healing
      phases during the bone regeneration process or geometrically different shapes of
      the regenerate.

PMID- 8156666
TI  - Long-term cost comparison of major limb salvage using the Ilizarov method versus
      amputation.
AB  - Hospital costs and professional fees of Ilizarov limb reconstruction patients
      were compared with hospital costs, professional fees, and prosthetic costs of
      lower-extremity amputation patients. Ten patients with tibial nonunions,
      osteomyelitis, infected nonunions, and/or bone defects underwent Ilizarov limb
      reconstruction while six patients with similar traumatic injuries underwent
      amputation (three acute and three delayed). The average age was 41 years for the
      Ilizarov group and 40 years for the amputation group. Both the Ilizarov and the
      amputation groups required an average of four surgical procedures. The average
      hospital length of stay was 16 days for the Ilizarov group and 25 days for the
      amputation group. The total average treatment time was 322 days for the Ilizarov
      group and 175 days for the amputation group. The total cost of the Ilizarov limb
      reconstruction averaged $59,213.71. The hospital costs and professional fees for
      the amputation group averaged $30,148.02 without prosthetic costs, but with the
      projected lifetime prosthetic costs included, averaged $403,199.18. This study
      suggests that Ilizarov limb reconstruction is cost-effective when compared with
      amputation when prosthetic costs are also considered.

PMID- 8156667
TI  - Distraction osteogenesis in the treatment of stiff hypertrophic nonunions using
      the Ilizarov apparatus.
AB  - The principle of treating stiff hypertrophic nonunions of long bones with
      distraction using the Ilizarov method permits simultaneous correction of axial
      deformity, angular deformity, translational deformity, shortening, and, in most
      instances, infection. Twenty-one hypertrophic nonunions in 19 patients were
      treated using the Ilizarov apparatus in distraction. Six of these patients had
      associated chronic osteomyelitis. Ilizarov treatment ranged from four to 12
      months (mean, 6.5 months). Follow-up time ranged from three to 11 years. Stable
      union was achieved in all patients. Angular, axial, and translational deformities
      were corrected in all patients; length discrepancies were corrected in 18 of 21
      patients (86%). Infection resolved in five of the six cases (83%) with chronic
      osteomyelitis. The sole complication was axial collapse of regenerate bone (in
      one patient with subsequent loss of 2 cm of lengthening) after premature removal
      of the Ilizarov fixator. Distraction osteogenesis in the treatment of stiff
      hypertrophic nonunions offers the most complete method of providing optimal limb
      function. The process allows the patient to maintain extremity mobility and
      weight bearing while undergoing treatment.

PMID- 8156668
TI  - A quality-based protocol for management of musculoskeletal injuries. A ten-year
      prospective outcome study.
AB  - Musculoskeletal injuries in the workplace are recognized as a major health and
      economic problem; however, little has been done to develop strategies that
      emphasize both quality and cost control. The purpose of this ten-year perspective
      investigation was to evaluate the use of quality-based standardized diagnostic
      and treatment protocols as part of an unbiased injury surveillance system. The
      program was evaluated in a public utility company with more than 5300 employees,
      and resulted in a measurable and long-term improvement in all outcome parameters
      measured: (1) The number of days lost from work and the number of new injuries
      reported fell by 55 and 51%, respectively. (2) The average time lost per injury
      dropped by 40%. (3) The number of surgeries performed decreased by 67%, and the
      operative success rate increased dramatically. (4) Finally, as an added benefit,
      there was a 60% reduction in expenditures for lost time and replacement wages,
      resulting in a cumulative ten-year savings of more than 4.1 million dollars. The
      program accomplished the goal of ensuring quality care in a prospective
      concurrent fashion. As an additional benefit, the program also reduced
      unjustified lost time and compensation costs through early functional return,
      efficient use of diagnostic studies, and avoidance of surgery whenever possible.
      Future emphasis on health-care delivery in the workers' compensation setting
      should concentrate on high-quality medical care, which will, in turn, lead to
      secondary cost savings.

PMID- 8156669
TI  - Should fusion accompany lumbar diskectomy? A medium-term answer.
AB  - The results of lumbar diskectomy for a sciatic syndrome in 90 patients were
      reviewed at an average of 8.5 years after operation. The best results were
      achieved in those patients who had their diskectomy within 12 months of the onset
      of their symptoms and through minimal approaches. Eighty-six percent of patients
      returned to gainful employment. Sixteen patients (18%) returned with low back
      pain attributable to the loss of intervertebral disk, of whom eight (9%) required
      secondary spinal fusion for control of pain. Seven of these latter patients
      obtained gratifying clinical and functional results. The findings suggest there
      is insufficient indication for routine spinal arthrodesis combined with lumbar
      disk excision. Those eight patients (9%) who developed a disabling
      postdiskectomy/postlaminectomy instability syndrome did so usually as a
      consequence of excessive bone and ligament excision and benefitted significantly
      from subsequent spinal arthrodesis.

PMID- 8156670
TI  - Arthroscopic distal clavicle excision. Technique and early results.
AB  - Since 1941, distal clavicle excision has been a reliable technique for
      alleviating pain caused by acromioclavicular joint arthritis. Disadvantages of
      the procedure include permanent shoulder weakness, a lengthy recovery time
      ranging from weeks to months before useful function of the extremity returns, and
      lack of cosmesis. By modifying the standard portals used to perform arthroscopic
      subacromial decompression, the authors have successfully excised the distal
      clavicle of ten consecutive patients. Using this arthroscopic technique, the
      surgical time averaged approximately one hour 40 minutes, blood loss was
      negligible, and there were no complications. Operations were performed in an
      outpatient setting. Five of ten patients missed work only on the day of surgery,
      and seven of ten patients required no formal physical therapy. All ten patients
      achieved a good or excellent result on the UCLA. Shoulder Scale for short-term
      follow-up evaluation. Postoperative radiographs documented adequate bone
      resection in all cases. In experienced hands, arthroscopic distal clavicle
      excision is an excellent substitute for the "open" procedure.

PMID- 8156671
TI  - Massive subacromial bursitis with rice bodies. Report of three cases, one of
      which was bilateral.
AB  - Multiple cartilaginous-like bodies (rice bodies) in joints or bursae may be the
      presenting sign of a more extensive underlying rheumatic condition. Three
      patients with massive subacromial bursae with rice bodies are described, one of
      whom had bilateral occurrence. In all patients, excision of the bursa and rice
      bodies relieved the symptoms. The underlying rheumatic condition continued its
      course, generally sparing the involved shoulder joint. Review of these cases
      reinforces the need to provide a thorough examination for systemic rheumatologic
      disease in patients diagnosed with this lesion.

PMID- 8156672
TI  - Distraction osteogenesis. A comparison of corticotomy techniques.
AB  - The left hindlimbs of 15 adult mongrel dogs were lengthened using the Ilizarov
      external fixator. Five dogs were assigned to each of three separate groups: (I)
      corticotomy; (II) osteotomy with multiple drill holes and an osteotome; (III)
      osteotomy with an oscillating saw. Distraction began on postoperative day seven
      and continued at a rate of 0.25 mm every six hours for 26 days. The regenerate
      segments were evaluated with weekly radiographs and Dual Energy Photon X-ray
      (DEPX) beginning at day seven. Barium perfusion studies and histologic
      preparations were also performed after the dogs were killed. Periosteal callus
      formation was apparent in all groups at two weeks, and endosteal callus appeared
      in Groups I and II at three to four weeks. Perfusion studies at the end of the
      distraction period demonstrated vessels bridging across the regenerate gap in
      Groups I and II. Vessels bridging the gap were diminished in the oscillating-saw
      Group III specimens. During the distraction period, the appearance and length of
      the regenerate bone was similar for each group radiographically and by DEPX
      scanning. No histologic differences were seen in Groups I and II. Three of the
      four tibias cut with the oscillating saw did not consolidate at ten weeks. A
      simple transverse osteotomy yields regenerate bone that is indistinguishable from
      the technically more difficult corticotomy. Use of the oscillating saw may lead
      to delayed consolidation.

PMID- 8156673
TI  - A survey of degenerative arterial change in the capsule of the hip joint in
      different disease states.
AB  - Degenerative arterial disease does affect the ligamentum teres and the capsule of
      the hip joint. In this investigation, the frequency of these changes was
      investigated in four groups of patients with hip disease. It is concluded that
      the highest incidence of all of degenerative arterial disease is found in elderly
      patients with subcapital fractures and in young patients with avascular necrosis
      of the femoral head after renal transplantation. The significance of this finding
      needs to be investigated further.

PMID- 8156674
TI  - Postoperative total hip prosthetic femoral head dislocations. Incidence,
      etiologic factors, and management.
AB  - Twenty-five dislocations occurred after 561 total hip arthroplasties performed by
      the author from 1971 to 1992. Acetabular shell and liner loosening must be
      differentiated from true dislocations. The dislocation rate of 5.49% in female
      patients was higher than the 2.8% rate in male patients. The 4.76% rate after 84
      total hip revisions was slightly higher than the 3.98% rate after 477 primary
      replacements. No dislocations occurred using the anterolateral approach for 53
      patients. Dislocation rates varied using different prosthetic systems for 508
      patients who had the posterolateral approach used. Femoral prostheses with larger
      neck diameters were more prone to dislocation. These differences were not
      statistically significant with the sample sizes used, according to the chi square
      test for equality of proportions. Fluoroscopy aided reduction of one multiplanar
      recurrent case. Single hip spica abduction casts with and without knee hinges
      used for three to four months, along with abduction isometric exercises, led to
      stability in six recurrent cases.

PMID- 8156675
TI  - Biological and clinical evaluation of distraction histogenesis.

PMID- 8156676
TI  - Treatment of the infected total hip arthroplasty with a two-stage reimplantation
      protocol.
AB  - Forty-four patients (46 hips) with infected total hip arthroplasties were
      evaluated. They were entered into a protocol that included resection
      arthroplasty, six weeks of intravenous antibiotics which obtained a minimum
      postpeak serum bactericidal titer of 1:8, and possible reimplantation. Thirty-two
      of 46 hips (70%) were reimplanted. At an average of 40 months (range, 24-74
      months) after reimplantation, infection recurred in three hips (9%). In two of
      the three recurrent infections, 1:8 bactericidal titers were not attained. Both
      of these hips were infected with gram-negative organisms. Minimum postpeak serum
      bactericidal titers of 1:8 were attained in 28 of 32 hips that were reimplanted,
      and only one of these hips (4%) had a recurrent infection (p = 0.035). The
      presence of retained cement after resection arthroplasty (ten hips) was not
      associated with recurrent infection. Fourteen hips (12 patients were not
      reimplanted as a result of a combination of factors, including inadequate bone
      stock, poor soft-tissue quality, and antibiotic resistance of the infecting
      organism. The treatment of an infected total hip arthroplasty with resection
      arthroplasty, six weeks of intravenous antibiotics that attains a minimum
      postpeak serum bactericidal titer of 1:8, and reimplantation can be an effective
      and safe treatment.

PMID- 8156677
TI  - Somatosensory evoked potential monitoring in the surgical treatment of acute,
      displaced acetabular fractures. Results of a prospective study.
AB  - A prospective protocol was developed to prevent iatrogenic nerve injury during
      the surgical treatment of acute, displaced acetabular fractures in 103 patients.
      The protocol included an independent neurologic evaluation and perioperative
      somatosensory evoked potential (SEP) monitoring (tibial division only). The
      incidence of posttraumatic nerve injury was 29% (30/103 patients). The incidence
      of postoperative nerve injury was 5% (5/103 patients): complete sciatic, 0;
      tibial division, 0; peroneal division, 5. Somatosensory evoked potential
      monitoring of the tibial division is effective in preventing injury to this
      division. If perioperative SEP monitoring is used, independent stimulation of the
      tibial and peroneal divisions is recommended. High-risk groups for perioperative
      injury to the sciatic nerve include those patients with significant posterior
      column or wall displacement or posttraumatic sciatic nerve injury.

PMID- 8156678
TI  - Innervation of the human knee joint and implications for surgery.
AB  - The anatomy of the articular and cutaneous nerves about the knee was investigated
      through 45 dissections of human anatomic specimens. The variability and location
      of these nerves are described and related to soft tissue and bony landmarks.
      Three constant nerves exist at the medial aspect of the knee, two of which have
      cutaneous territories that extend across the midline. The third nerve is
      articular. Two lateral articular nerves were found consistently in relation to
      reliable landmarks. The innervation to the lateral knee skin is variable from
      either the lateral femoral cutaneous nerve or branches of the femoral nerve. This
      anatomy provides a basis for nerve blocks and selective denervation in the
      treatment of knee pain.

PMID- 8156679
TI  - The function of below-knee amputee versus the patient with salvaged grade III
      tibial fracture.
AB  - This retrospective study compares the end-stage function of the traumatic below
      knee amputee with that of the patient with salvaged Grade III tibial fracture.
      Twenty-four patients, 12 below-knee amputees and 12 with salvaged tibiae, were
      interviewed and examined one year or more after the completion of treatment.
      Emphasis was on function of the limb, the patient, and the quality of life. The
      early amputees had higher scores, fewer operations, and six-week hospitalization
      on average, and returned to work and sport within six months. Neither the
      amputees, nor the salvaged group, functioned entirely normally. Most patients
      made significant alterations to work and sporting activities, and approximately
      one third believed there was deterioration in the quality of life. These results
      suggest that amputation should be strongly considered when confronted with a
      borderline salvageable tibial injury or prolonged salvage attempts.

PMID- 8156680
TI  - Unicompartmental knee arthroplasty. Sequential radiographic and scintigraphic
      imaging with an average five-year follow-up.
AB  - Clinical, radiographic, and scintigraphic results of 33 consecutive
      unicompartmental knee arthroplasties were reviewed after a mean follow-up period
      of 68 months (range, 24 to 112 months). Clinical grades employing criteria
      established by the Hospital for Special Surgery showed 74% good to excellent and
      11% fair to poor results. Four knees (15%) required revision to a total knee
      arthroplasty after an average postoperative interval of 7.4 years. Within the
      subset of surviving medial compartment arthroplasties (23 knees), superior
      clinical results were associated with a central or slightly medialized mechanical
      axis (p < 0.05). Periprosthetic radiolucency showed no correlation with clinical
      scores or failures resulting in revision surgery. There was no radiographic
      evidence of progressive arthrosis within the unreplaced compartments. Comparative
      analysis of preoperative and annual postoperative technetium bone scans showed no
      temporally related changes indicative of impending prosthetic failure or disease
      progression within the unoperated compartments. The surgically treated
      compartments maintained uniformly intense femorotibial activity, whereas the
      unoperated compartments, including the patellofemoral joint, remained
      scintigraphically quiescent. Disease progression in unreplaced compartments is
      unusual after contemporary unicompartmental knee arthroplasty. Most failures and
      poor results arise from mechanical inadequacies amendable to surgical technique
      and/or future design considerations.

PMID- 8156681
TI  - Compartment syndrome in the well leg resulting from fracture-table positioning.
AB  - A variety of patient positioning options exist on modern fracture tables for use
      during intramedullary nailing procedures. With the advent of interlocking and
      reconstruction nailing, some of these procedures can be complicated and
      prolonged. The use of the hemilithotomy position for prolonged intramedullary
      nailing procedures can result in the development of a compartment syndrome in the
      uninjured leg, no matter what type of suspension device is used for that leg. The
      occurrence of this iatrogenic injury in the patient's well leg can be devastating
      in light of the contralateral fracture. Two patients at this institution have had
      such a condition in the past two years, and the authors have revised their
      positioning procedures. Review of the surgical literature shows that this
      complication has been seen in urologic, gynecologic, and general surgical
      patients, but has not been widely reported in the orthopaedic population.
      Recommendations for avoiding this problem include the use of other positions or
      distraction devices when performing intramedullary nailings, or, when the
      hemilithotomy position cannot be avoided, early intraoperative repositioning of
      the leg when possible.

PMID- 8156682
TI  - Age- and joint-specific risk of initial heterotopic ossification in patients who
      have fibrodysplasia ossificans progressiva.
AB  - Using data from a survey of 44 patients who have fibrodysplasia ossificans
      progressiva, age- and joint-specific risks of new joint involvement were
      estimated using parametric and nonparametric statistical methods. Regions in
      which the risk of heterotopic ossification appears to remain constant with age
      include the neck, spine, shoulders, elbows, and ankles. Regions with apparently
      increasing risk include the jaw, wrists, hips, and knees. This analysis allows
      clinicians to estimate the risk of new involvement for any joint at any patient
      age, as well as the fraction of patients with uninvolved joints at any age. The
      variation of ossification risk by joint provides a clinically useful guide to the
      patterns of progression of the disease. Such a guide will help in planning for
      individual patient needs, as well as anticipating auxiliary social services and
      rehabilitation programs.

PMID- 8156683
TI  - Chronologic outcome of surgical tendoachilles lengthening and natural history of
      gastroc-soleus contracture in cerebral palsy. A two-part study.
AB  - Medical records of 59 patients with cerebral palsy were reviewed retrospectively
      to evaluate results of tendoachilles lengthening. Surgical lengthening resulted
      in highly significant (p < 0.0001) initial average gains in dorsiflexion compared
      with baseline. These average improvements maintained their statistical
      significance for seven years postoperatively. The arc of motion was not
      significantly different postoperatively. The initial ambulatory level was
      improved in 55% of the patients and maintained in the remainder. However, 14
      ankles (11.9%) in eight patients (13.6%) required repeat tendoachilles
      lengthening during the study period, primarily after gastrocnemius procedures.
      Calcaneus deformity occurred in 1.7% of the surgically treated ankles. To
      evaluate the potential for spontaneous improvement over time in fixed equinus
      deformity, the records of a group of 68 additional cerebral palsy patients were
      reviewed. Patients treated nonoperatively despite two examinations that
      demonstrated fixed lack of dorsiflexion, while not representing a true control
      group, showed no spontaneous improvement in equinus deformity through seven years
      postoperatively.

PMID- 8156684
TI  - Experimental healing of distraction osteogenesis comparing metaphyseal with
      diaphyseal sites.
AB  - Distraction osteogenesis was performed on 32 adult dogs to compare bone healing
      at metaphyseal and diaphyseal sites. Sixteen dogs underwent proximal metaphyseal
      corticotomy and 16 dogs underwent middiaphyseal corticotomy of the left tibiae
      for gradual lengthening. Each major group was then divided into four subgroups of
      four dogs each on the basis of zero-, seven-, 14- and 21-day latency periods. The
      standard radiograph, quantitative computer tomography density, and bone-healing
      index were used to evaluate new bone formation and consolidation. A distraction
      rate of 1 mm per day for four weeks created an average elongation of 23.9 +/- 3.7
      mm in the metaphyseal groups and 23.8 +/- 2.0 mm in the diaphyseal groups,
      excluding nine premature consolidations. In the 16 metaphyseal lengthenings,
      there were six premature consolidations (37.5%): four with a 21-day latency, two
      with a 14-day latency, and one nonunion (6.2%). In the 16 diaphyseal
      lengthenings, three fused prematurely (18.7%), two with a 21-day latency and one
      incomplete corticotomy with a seven-day latency. Three lengthenings of the
      diaphyseal group resulted in nonunion (18.7%). All animals, metaphyseal and
      diaphyseal, successfully bridged the distraction gap after a zero-day latency.
      The bone-healing index showed that new bone consolidation was best with a zero
      day latency in metaphyseal (22 +/- 7.6 days/cm) and diaphyseal lengthening (26.5
      +/- 6.5 days/cm). Comparing the minimum quantitative computer tomography density
      ratio of the experimental side with the contralateral side indicated a
      significant difference at the end of distraction (p = 0.001), at fixator removal
      (p = 0.001), and when the dogs were killed (p = 0.04).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8156685
TI  - Flexion-type Salter II fracture of the proximal tibia. Proposed mechanism of
      injury and two case studies.
AB  - An uncommon fracture of the proximal tibial epiphysis is described in two cases.
      A flexion-type Salter II fracture of the proximal tibia resulting from a
      partially closed physis can be reduced easily and appears to have no long-lasting
      effects. Radiographic review of the adolescent knees showed that physeal closure
      of the proximal tibial epiphysis proceeds from posterior to anterior, thereby
      making this particular fracture more likely during this phase of development.

PMID- 8156686
TI  - Osteoid osteoma of the coracoid process. Excision by posterior approach. A case
      report.
AB  - Scapular involvement by osteoid osteoma is rare and seems not to have been
      reported previously in the literature. This is a case report of an osteoid
      osteoma that involved the posterior base of the coracoid process of the scapula
      in a 14-year-old boy.

PMID- 8156687
TI  - Bovine bone morphogenetic protein (bBMP/NCP)-induced repair of skull trephine
      defects in pigs.
AB  - Bovine bone morphogenetic protein and associated noncollagenous proteins
      (bBMP/NCP) were implanted in skull trephine defects, 14 and 22 mm in diameter, in
      adult minipigs. The defects were larger than the critical size for repair of
      cranial bones in pigs observed for a period of six to 16 weeks. The trephines
      were placed either in the nasal bone at eye level, or in the frontal bone. In
      minipigs the repair was more advanced in trephines in the frontal bone than in
      the nasal region, but was incomplete in either bone bed. As in dogs, implants of
      bBMP/NCP in heterotopic sites were resorbed before a competent cell population
      could respond. Serum anti-BMP antibody was elevated. The IgG levels of the
      antibody titer showed a clearcut dose-response; the level was significantly
      higher in one pig with implants of 85 mg of bBMP/NCP proteins in a frontal bone
      trephine.

PMID- 8156688
TI  - Enhancement of periosteal chondrogenesis in vitro. Dose-response for transforming
      growth factor-beta 1 (TGF-beta 1).
AB  - Transforming growth factor-beta 1 (TGF-beta 1) has been shown to stimulate
      chondrogenesis in periosteal explants cultured in agarose suspension. In this
      study, the dose-response curve for such enhancement was measured. Periosteal
      explants and fascia lata were harvested from two-month-old rabbits, cultured for
      six weeks with 0, 0.1, 1, 5, 10, 50, or 100 ng/mL TGF-beta 1 in agarose
      suspension, then analyzed by histomorphometry and quantitative collagen typing.
      Cartilage was produced by seven of 11 (64%) of the control periosteal explants
      cultured in agarose suspension without TGF-beta 1. Transforming growth factor
      beta 1 enhanced chondrogenesis in a dose-dependent manner in the range 0.1-100
      ng/mL. It was most effective at 50 ng/mL. At very high doses (50 and 100 ng/mL)
      of TGF-beta 1, even fascia lata control explants exhibited chondrogenesis. These
      data indicate that TGF-beta 1 can induce differentiation toward cartilage
      production as well as enhance it once it has been initiated.

PMID- 8156689
TI  - The vascular response to fracture micromovement.
AB  - Micromovement has been shown to promote the healing of experimental fractures,
      but its role in the clinical management of fractures with soft-tissue injury is
      less certain. In a 2-mm transverse osteotomy of the ovine tibia held in an
      instrumented external fixator, axial interfragmentary displacement was quantified
      in vivo for six weeks after osteotomy. Group I (n = 11) had an axial fixation
      stiffness of 460 N/mm and Group II (n = 12) had a stiffness of 238 N/mm. With a
      25% difference in micromovement, a fourfold change in corticomedullary blood flow
      was observed at two weeks after osteotomy (p < 0.01). Although by six weeks
      mechanical properties in torsion were similar, there were marked differences in
      the periosteal cross-sectional perimeter, area, and intracortical porosity that
      complemented the hemodynamic changes. The early vascular response is very
      sensitive to the initial mechanical environment, and appears to precede and
      determine the organization of osteogenesis. Further understanding of this
      relationship may prove to be of direct clinical relevance in the augmentation of
      healing of devascularized diaphyseal fractures.

PMID- 8156690
TI  - Effect of methotrexate in the biology of free vascularized bone grafts. A
      comparative experimental study in the dog.
AB  - To evaluate the effects of methotrexate (MTX) on the biology of a vascularized
      bone graft (VBG), a study of adult dogs was performed. Different protocols of
      treatment using MTX, with or without the administration of citrovorum rescue
      factor (CRF), were studied. A controlled experiment involving 18 dogs was
      performed to evaluate the biology of a free vascularized rib graft used to
      reconstruct a 7-cm segmental defect in the femoral shaft. The grafts were
      examined at five, eight, and 14 weeks after surgery. Bone union, remodeling, and
      vasculature were found to be normal, despite a high rate of cortical necrosis in
      the early follow-up periods (30-40%). In a similar group of VBG, MTX was
      administered at a dose of 1500 mg/m2 body surface (intravenous) from the 14th
      postoperative day, every three weeks, until the animals were killed. Citrovorum
      rescue factor was administered to avoid the toxic side effects of the MTX. The
      results of this group did not differ from those of the control group as far as
      bone union, remodeling, vasculature, and viability of the graft were concerned.
      Methotrexate did not, for the most part, affect the biology of a free
      vascularized bone graft.

PMID- 8156691
TI  - Recombinant human bone morphogenetic protein-7 induces healing in a canine long
      bone segmental defect model.
AB  - An ulnar segmental defect model was used in adult male dogs to examine the effect
      of recombinant human bone morphogenetic protein-7 (recombinant human Osteogenic
      Protein-1 [rhOP-1]; Creative Biomolecules, Hopkinton, Massachusetts) on new bone
      induction and healing, and to test the mechanical strength of healed 2.5-cm
      segmental bone defects. The rhOP-1 composites consisted of a carrier of 500 mg of
      demineralized, guanidine-extracted, insoluble bovine bone matrix (collagen
      carrier), reconstituted with rhOP-1. Six animals received 1200 micrograms rhOP-1
      unilaterally and were killed at 12 weeks for torsional load-to-failure testing
      using the contralateral side as a control. Two further animals received varying
      amounts of rhOP-1 bilaterally and were studied histologically. All defect sites
      receiving rhOP-1 were completely bridged radiographically by eight weeks. A
      control composite, containing no rhOP-1, failed to induce new bone formation at
      any time. Histologically, rhOP-1-treated sites examined at 16 weeks had formation
      of new cortical and cancellous bone, with normal appearing marrow elements in the
      reconstituted medullary canal. The torsional strength of the rhOP-1-implanted
      ulnae averaged 72% of control (range, 30-99%). The angular deformation to failure
      averaged 92% of control (range, 39-122%). The energy absorption to failure
      averaged 67% of control (range, 27-111%). This study demonstrates the efficacy of
      rhOP-1 in healing segmental osteoperiosteal defects in a canine model.

PMID- 8156692
TI  - Variables affecting time to bone healing during limb lengthening.
AB  - Radiographs and charts of 114 consecutive patients who underwent 140 lower
      extremity bone-segment lengthening procedures using the Ilizarov external fixator
      were reviewed. Patient age, bone segment (femur, tibia), corticotomy level
      (metaphyseal, diaphyseal, double level), and distraction gap (DG) were recorded.
      Distraction-consolidation time (DCT) was defined as the interval in months from
      the date of the corticotomy until the DG was healed according to radiographic and
      manual testing criteria. Distraction-consolidation time had a direct linear
      relationship with the magnitude of the DG. Distraction--consolidation time versus
      DG was significantly less for femoral than tibial lengthening. Patients 20 years
      and older healed slower than patients younger than the age of 20 years. Patients
      20 to 29 years old healed faster than patients older than 30 years and slower
      than patients younger than 20 years. Diaphyseal lengthening healed more slowly
      than metaphyseal lengthening. Double-level lengthening reduced the DCT when the
      DG was greater than 4 cm. Distraction--consolidation index--DCT divided by DG-
      was not a constant. Distraction--consolidation index decreased with increasing
      DG. To facilitate prediction of bone-healing time, graphs were developed
      demonstrating the average treatment time +/- 2 SD expected for a specific amount
      of lengthening, considering the bone segment, the level of osteotomy, and the age
      of the patient.

PMID- 8156693
TI  - Treatment of deformity secondary to metabolic bone disease with the Ilizarov
      technique.
AB  - Eighteen limb segments in eight patients with lower limb deformities secondary to
      metabolic bone disease underwent correction using the Ilizarov technique. Eleven
      femora and seven tibiae were treated for deformities with magnitudes of 12
      degrees to 58 degrees. Total treatment time averaged 12 weeks from application to
      removal of the fixator. With one exception, correction was performed at the rate
      of 0.5 mm daily in two increments. Complications were limited to several pin
      tract infections and mild translational deformity in two patients. Healing index
      averaged approximately twice that seen in pediatric femoral lengthening and was
      25% greater than for patients undergoing tibial lengthening. The lack of implants
      requiring removal, modularity, and reasonable treatment time make this technique
      an attractive alternative to conventional osteotomy for management of limb-length
      deformity associated with metabolic bone disease.

PMID- 8156694
TI  - On the means of lengthening, in the lower limbs, the muscles and tissues which
      are shortened through deformity. 1904.

PMID- 8156695
TI  - Noninvasive determination of bone stiffness for distraction osteogenesis by
      quantitative computed tomography scans.
AB  - Apparent density of canine tibial specimens was correlated to measured
      quantitative computed tomography (QCT) numbers, and a conversion equation was
      derived. Finite element analysis models of canine tibiae were constructed using
      spatial coordinates of converted QCT data. Two QCT-derived finite elemental
      analysis models were constructed for a pair of matched tibiae: one lengthened 15%
      by distraction osteogenesis and one contralateral control. Two equations relating
      the modulus of elasticity to apparent density were used. These models were then
      verified mechanically by measuring strains of the two specimens under applied
      load. Equation I correlated best with measured strains in the less-dense
      regenerate bone of the distracted tibia (R2 = 0.914, p = 0.0028, n = 6); Equation
      II performed best in the denser control tibia (R2 = 0.820, p = 0.0129, n = 6).
      These results demonstrate that the stiffness of tubular bones, including cortical
      and heterogenous cancellous structure, can be accurately predicted by a
      noninvasive QCT scan.

PMID- 8156696
TI  - Knee range of motion in isolated femoral lengthening.
AB  - Twenty-five patients underwent isolated Ilizarov femoral lengthenings (mean
      lengthening, 6 cm). A retrospective review of the charts showed the specific
      changes in knee range of motion (ROM) during lengthening, after removal of the
      frame, and at the final follow-up examination. A decrease in ROM was seen during
      lengthening to an average minimum of 37 degrees +/- 15 degrees. Toward the end of
      the consolidation phase, improvement to 69 degrees +/- 28 degrees was noted. A
      progressive increase in ROM was seen after frame removal. Mean preoperative
      flexion was 127 degrees +/- 16 degrees, and at follow-up flexion was 122 degrees
      +/- 23 degrees (p = 0.191). Of the five patients who did not achieve 120 degrees
      flexion at the final follow-up examination, three had a diminished ROM (average,
      107 degrees) at the outset. Two patients lost more than 15% of their preoperative
      flexion. There was no correlation noted between worst ROM (during lengthening)
      and final ROM at the last follow-up examination.

PMID- 8156697
TI  - Femoral forces during limb lengthening in children.
AB  - A system was designed to measure forces during femoral lengthening using force
      transducers on an Ilizarov femoral frame. Measurements were made in three
      teenaged subjects overnight and during weight bearing. A progressive increase in
      axial load secondary to distraction was seen, forces peaking at 428, 447, and 673
      N for the three subjects. Little change in force transmitted by the frame was
      observed during weight bearing. Measurements taken before and after each
      individual lengthening showed no change in axial force or bending moment (p >
      0.01). A diurnal variation of axial load was found (p < 0.01). Forces at midnight
      were greater than in the morning in all the subjects, with a mean difference of
      113 N (p < 0.01). Distraction forces measured in the femur during distraction are
      greater than those previously measured in the tibia. Evidence exists that the
      callus is stiff and may be the origin of these forces.

PMID- 8156698
TI  - Joint reaction forces during femoral lengthening.
AB  - The purpose of this study was to observe the reactive force across the hip and
      knee joint in a cadaver study during simulated femoral lengthening. Load cells
      were placed in the hip and knee joints while force measurements were taken after
      every 1 mm of lengthening. The lengthening was performed on one side with a
      distal osteotomy and on the other with a proximal osteotomy to determine if the
      level of the osteotomy had any affect on the forces across the proximal and
      distal joints. The study showed that the forces at the hip and knee joints
      increased during lengthening. The proximal osteotomy appeared to increase the
      amount of force at the hip joint. The force at the knee joint was less affected
      by the level of the osteotomy. The relative force between the knee and the hip
      was approximately a 2:1 ratio with a distal corticotomy as opposed to a 1:1 ratio
      with a proximal osteotomy. From this study, it is suggested that if instability
      of the hip is a concern during femoral lengthening, then a distal osteotomy
      should be used.

PMID- 8156699
TI  - The effect of limb lengthening on articular cartilage. An experimental study.
AB  - Limb-length discrepancy is a relatively common problem in children. Limb
      lengthening has traditionally been indicated for projected or actual length
      discrepancies exceeding 5 cm. Rapid distraction methods of limb lengthening,
      introduced by Codivilla and popularized by Wagner, have had unacceptably high
      complication rates. Gradual incremental distraction methods have resulted in
      improved bone genesis, yet the problems of soft-tissue contracture and decreased
      joint range of motion have not been solved. A pilot canine study was undertaken
      to prove the hypothesis that extended limb lengthening can result in injury to
      articular cartilage. Seven mature beagles underwent application of a transosseous
      circular fixator to their right femora and a periosteal-sparing osteotomy of the
      distal right femora. Distraction to a 30% increase over initial femoral length
      was performed at a rate of 0.75 mm daily in three increments in six dogs. One dog
      served as a sham-operated control. Free cage activity was allowed
      postoperatively. At the conclusion of lengthening, experimental and contralateral
      knee joints were harvested. They were assessed grossly, decalcified, and
      sectioned sagittally through the femoral and tibial condylar contact surfaces.
      All sections were stained with safranin-O and assessed histologically. One dog
      was eliminated from the study because of pin-site sepsis. The five animals who
      completed lengthening demonstrated gross cartilage fibrillation. Loss of
      proteoglycan staining was seen in three animals and frank cartilage necrosis in
      two. The control limbs and sham-operated limb demonstrated no gross or
      microscopic abnormalities. These findings confirm direct evidence of cartilage
      injury during limb lengthening.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156700
TI  - Mechanical forces as predictors of healing during tibial lengthening by
      distraction osteogenesis.
AB  - Direct axial loads were measured weekly during a 15% left tibial lengthening in
      21 skeletally mature dogs using three in-line load cells mounted between the
      rings of an Ilizarov external fixator. The loads increased linearly over time to
      a maximum at the end of distraction (Week 4). The metaphyseal lengthening sites
      (mean, 155 N) generated significantly higher loads than diaphyseal sites (mean,
      111 N). Stress was calculated by dividing measured load by the computed
      tomographic-measured cross-sectional area of each distraction osteogenesis site;
      the metaphyseal and diaphyseal groups demonstrated equal stress at each time
      point with a maximum of 47 N/cm2 at the end of distraction. Six premature
      consolidations occurred that demonstrated loads significantly greater than 200 N
      by Week 2 of distraction. Three nonunions occurred that had significantly lower
      loads measured by Week 3 of distraction (mean, 60 N or 26 N/cm2).

PMID- 8156701
TI  - Mechanical distraction for treatment of severe knee flexion contractures.
AB  - Ten patients (14 knees) with severe knee flexion contractures were treated by
      gradual mechanical distraction using either the Ilizarov or Orthofix external
      fixator. Range of motion improved from an average flexion contracture of 60
      degrees before surgery to 16 degrees at the follow-up evaluation. Range of motion
      results were graded good or excellent in five knees, fair in two knees, and poor
      in three knees. Average total arc of motion remained essentially unchanged when
      comparing the preoperative (59 degrees) with the follow-up results (63 degrees).
      However, the functional position of this arc improved significantly. Problems
      encountered included a "rebound" phenomena after frame removal, with loss of the
      temporarily increased total arc of motion. The role of hamstring tenotomy and
      radical posterior knee release remains unclear.

PMID- 8156702
TI  - Correction of the neglected clubfoot by the Ilizarov method.
AB  - Untreated clubfoot deformity remains a significant problem for the orthopaedist
      practicing in Third World countries. Using gradual distraction applied through
      the Ilizarov external fixator, 12 cases of neglected clubfoot deformity in seven
      adult patients were successfully treated at the General Hospital for the Mexican
      Institute of Social Security. The two men and five women ranged in age from 19 to
      42 years (mean, 27 years). These minimally constrained frames required five to
      eight months of fixation time to achieve the correction. When a plantar-grade
      position was achieved, the fixator was removed and a below-knee walking cast
      applied. The follow-up time ranged from two to five years. Complete correction
      was obtained in all patients, and adductus deformity recurred in three. Feet were
      stiff before and after treatment, especially the forefoot. Postoperative
      ambulation seemed to restore some motion.

PMID- 8156703
TI  - Articulated distraction of the hip. Conservative surgery for arthritis in young
      patients.
AB  - Between 1979 and 1982, 80 patients with a variety of hip diseases were treated
      with articulated distraction of the hip. The patients ranged from nine to 69
      years of age (mean, 34 years). The primary diagnoses were avascular necrosis,
      osteoarthrosis, and chondrolysis. A standard dynamic axial fixator with a single
      axis articulating unit was used to create a 5-mm joint space. The fixator allowed
      flexion and extension motion and remained in place for six to ten weeks. The
      follow-up period ranged from five to eight years. Assessment was performed by
      questionnaire, clinical, and radiographic review. The results were poor in 24
      patients who were either older than 45 years of age or had a diagnosis of
      inflammatory arthropathy. Forty-two good results were found in the 59 patients
      younger than 45 years with osteoarthrosis, hip dysplasia, avascular necrosis, and
      chondrolysis. Only four patients older than 45 years of age had a good result. No
      serious complications occurred.

PMID- 8156704
TI  - [Idiopathic pure sudomotor failure].
AB  - We describe three cases of acquired generalized anhidrosis without other
      autonomic and somatic nervous dysfunctions (idiopathic pure sudomotor failure;
      IPSF) and a review of the literature was made in regard to the clinical features
      of this disease. Patient 1. A 17-year-old man was found to be severely anhidrotic
      and intolerant to heart loading, which produced an immediate sharp pain over the
      entire body surface in April, 1989. Sudden and spontaneous remission occurred in
      July, 1990, but relapsed six months later. He was admitted to our hospital
      seeking for therapy in April, 1991. There were no abnormal findings on physical
      and neurological examinations except for anhidrosis. Patient 2. A 14-year-old boy
      was admitted to our hospital in March 1991 with complaints of intolerance to
      heart loading and sharp pain, which had begun ten months before admission.
      Physical and neurological examinations revealed no abnormal findings except for
      anhidrosis. Patient 3. A 21-year-old woman suddenly experienced a burning
      sensation in the whole body in 19th, February, 1991, which was followed by severe
      pain. She was admitted to our hospital in the next day. Apart from sensory
      impairment of glove and stocking type, neurological examination revealed no
      abnormal findings. Reflex sweating to pilocarpine was absent in all three cases,
      suggesting abnormality in the postganglionic sudomotor nerves or cholinergic
      receptors. Skin biopsy was performed in one patient (patient 1), and revealed no
      abnormalities of the sweat glands and ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156705
TI  - [Difference of cerebral arteriolosclerosis between the deep and subcortical white
      matter in normal aging and vascular dementia of Binswanger type].
AB  - A comparative pathological study of arteriosclerosis was conducted between the
      deep white matter (M1) and the subcortical white matter (M2) to investigate the
      difference in the arteriolar changes in normally-aging individuals and those
      presenting vascular dementia. The arterioles (20-100 microns in outer diameter)
      of 95 autopsied brains were examined (56 control cases; C group, 24 hypertensive
      cases; HT group, and 15 Binswanger type vascular dementia cases; VD group). In C
      group, the primary pathological change was adventitial proliferation (AP), which
      was significantly more pronounced in M1 than in M2. AP in M1 was found to have
      advanced promptly with aging, while AP in M2 advanced mildly. AP in M1 was much
      more pronounced in HT group than in the age-matched C group, but little
      difference in M2 was observed between the two groups. AP in VD group was more
      pronounced in M2 than in M1 compared with HT group. These findings indicate that
      AP in M1 occurs prior to that in M2 in the process of normal aging, and that AP,
      in M2 as well as in M1, may play an important role in the pathogenesis of
      Binswanger type vascular dementia.

PMID- 8156706
TI  - [Intravenous immunoglobulin therapy in multifocal motor neuropathy].
AB  - We treated ten consecutive patients with multifocal motor neuropathy (MMN) with
      high-dose intravenous immunoglobulin. Ages ranged 18 to 58 years, with disease
      duration of 9 months to 8 years. We treated them with 0.2 g/kg of human
      immunoglobulin for 6 consecutive days. All but one showed a clinical improvement
      starting within a week after the first infusion. The functional improvement
      ranged from marked to mild degree. In six patients, the clinical effect abolished
      within 2 months. Improvement was persistent for more than 6 months in the other
      three. In only two patients conduction block improved after the treatment. The
      discrepancy may result from an increased threshold of remyelinated or chronically
      demyelinated fibers for excitation. Side effects were not documented. This pilot
      study indicates that immunoglobulin may be a safe and effective therapy for MMN.

PMID- 8156707
TI  - [Altered energy metabolism in Alzheimer's disease].
AB  - To evaluate the energy metabolic status of Alzheimer's disease, we examined the
      cerebral arteriovenous differences of glucose, oxygen, lactate, pyruvate, ketone
      bodies, and free fatty acids and N-isopropyl-p-(123I) iodoamphetamine (IMP)
      single-photon emission computed tomography in 5 patients with Alzheimer's disease
      (4 male and 1 female patients; mean age of 64.80 +/- 8.47 years). Compared with 5
      age matched normal control subjects (4 males and 1 female; mean age of 63.20 +/-
      10.76 years), the patients showed significantly decreased regional cerebral blood
      flow only in the parietotemporal region. The global cerebral glucose metabolic
      rate (CMRGlu) had significantly low value, whereas the global cerebral oxygen
      metabolic rate (CMRO2) was not changed. The metabolic ratio (CMRO2/CMRGlu) was
      significantly elevated to 9.73 in the patients with Alzheimer's disease, compared
      with 5.50 in the normal controls. The cerebral metabolic rates of ketone bodies
      and free fatty acids were unchanged. The cerebral pyruvate output was
      significantly decreased. The cerebral lactate output became negative, but the
      decrease did not reach statistical significance. We concluded that the markedly
      elevated metabolic ratio suggests an altered energy metabolism in Alzheimer's
      disease.

PMID- 8156708
TI  - [MRI findings in patients with vertigo and dizziness possibly arising from
      vertebrobasilar insufficiency].
AB  - In order to evaluate diagnostic usefulness of MRI in vertebrobasilar
      insufficiency (VBI), we performed magnetic resonance imaging (MRI) and MR
      angiography (MRA) in 90 patients presenting vertigo and dizziness as an initial
      and cardinal complaint. High signals observed by T2-weighted imaging in the basal
      ganglia (44.4%) or pontine base (48.9%) were more frequently seen in the possible
      VBI group than in the controls (p < 0.001). The electronystagmographical
      abnormalities were commonly observed in the patients with a high signal in the
      pontine base, reflecting diffuse ischemic lesion in the territory of the
      vertebrobasilar system. Vertebral artery asymmetry (45.6%) or basilar artery
      twisting (41.1%) as shown by MRA was also significantly more frequent in the
      patients than in the controls (p < 0.05). In conclusion, MRI and MRA were
      considered to be useful in making a clinical diagnosis of VBI in such patients.

PMID- 8156709
TI  - [An adult case of congenital myopathy--coexistence of nemaline rods and core-like
      structures].
AB  - A 42-year-old female complained of exertional dyspnea and sleep disturbance. Her
      face was elongated longitudinally and the hard palate was narrow and high-arched.
      She has slender musculature and kyphoscoliosis. She was dysphonic and could not
      walk on her heels. Muscles in the face, upper arm, pelvic girdle and thigh were
      atrophic. Muscle weakness was detected in the neck, tibialis anterior, ilipsoas
      and other hip muscles, and ranged between 3- and 4 by the manual muscle testing.
      Electromyography showed definite myogenic abnormalities in all the muscle
      examined. No abnormality was found on the routine examination of blood, as was
      the motor and sensory nerve conduction velocity. Her vital capacity was 0.91 L,
      i.e., 35% of the expected value, suggesting a severe restrictive respiration. The
      arterial blood gas analysis revealed hypoxia, hypercapnia and desaturation. The
      blood gas data worsened when she was asleep, because of increased
      hypoventilation. Muscle biopsy of the biceps brachii showed a marked variation in
      the muscle fiber size. The type 1 muscle fiber was predominant. Many fibers
      contained nemaline rods and/or core-like structures. Some fibers contained both
      nemaline and core-like structures. This core-like structures were not stained
      with NADH-TR and ATPase reactions, and about 40-100 microns in the longitudinal
      extension. In this context, typical central cores have not been observed in the
      present case. No association of nemaline rods and core-like structures in the
      same muscle fiber has been reported, although a close relationship of the two
      structures has been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156710
TI  - [Enhanced regeneration of terminal axons after hyperbaric oxygen therapy in a
      patient resembling progressive postpoliomyelitis muscular atrophy].
AB  - We found an electromyographical proof of reconstruction of the motor nerve
      terminals following hyperbaric oxygen therapy. A 38-year-old man who had been
      partially recovered for thirty four months from acute onset paraplegia following
      a gastrointestinal infection developed progressive muscular atrophy and weakness
      of the lower limbs, and was first admitted to our hospital. Cerebrospinal fluid
      examination was normal and nerve conduction studies showed small compound muscle
      action potentials without an evidence of segmental demyelination. There were
      ample fibrillation potentials on electromyography. Single fiber electromyography
      (SFEMG) showed increased fiber density, abnormal jitter and blockings without
      neurogenic jitter, which were similar to findings in post-poliomyelitis syndrome.
      He was treated by hyperbaric oxygen consisting of two hour exposures to pressures
      of two atmospheres breathing 100% oxygen. These exposures continued for a month
      daily, and thereafter once a week for one year. Clinical improvement of the
      weakness and a decrease in amount of fibrillation potentials occurred on and
      after a month after treatment. We found significant changes on SFEMG a year
      later. There were increased fiber densities and decreased mean values of
      consecutive differences. These changes indicate diminished degeneration and
      enhanced regeneration of the terminal axons. We think that hyperbaric oxygen has
      a beneficial effect on oxygen metabolism of remaining motoneurons which may not
      be able to maintain excessive metabolic demands of all their sprouting axons.

PMID- 8156711
TI  - [Event related potentials and reaction time on auditory discrimination tasks (2nd
      report)--a study by trial-to-trial analysis].
AB  - Latency variability for single trial in the 4 components (N100, P200, N200 and
      P300) of the auditory event related potentials (ERP) and the temporal
      relationship to the choice reaction time (RT) were investigated in 11 normal
      subjects. Identification of each latency on single trials was derived by using a
      correlational-template procedure. Results showed that the mean value of the
      single trial latency in the 4 components was close to the peak latency in the
      averaged waveform. Significantly larger coefficient of variation was obtained for
      the N100 component and RT, when compared to the other components. Higher
      correlation between single trial latency and RT was found for N200 and P300
      components. The P300 component latency yielded a significant temporal effect
      across trials (p < 0.05) showing increases in its latency in the later trials,
      whereas none of the RT did. These results may indicate that the P300 component
      latency is influenced directly by subtle changes in cerebral activities during an
      initial stage of human cognitive function occurring in each trial, whereas RT is
      additionally influenced by greater functional fluctuation during the process of
      motor execution for making responses.

PMID- 8156712
TI  - [Chorea-ballism associated with nonketotic hyperglycemia and presenting with
      bilateral hyperintensity of the putamen on MR T1-weighted images--a case report].
AB  - A 55-year-old woman was admitted to our hospital with abrupt onset of chorea
      ballism in the right arm and both legs. She had thirst before admission. The
      blood glucose level was 976 mg/dl, the serum osmolality was 335 mOsm/l, and there
      was slight ketonuria on admission. Even after normalization of the blood glucose
      level choreiform movement of the right arm and leg continued. Brain CT showed
      bilateral and symmetrical high density of the putamen on admission, which
      diminished at 32 days leaving an area of low density. This suggested that the
      high density was not calcification. There was no mass affect. Symmetrical high
      intensity of the bilateral putamen on MR T1-weighted images which was slight on
      admission increased in intensity after 2 months, but disappeared 4 months after
      the onset in association with the disappearance of choreiform movement. The
      abnormality in the putamen was considered to be the cause of her involuntary
      movements. In nonketotic hyperglycemia, high intensity basal ganglia lesions on
      T1-weighted MR images have previously not been reported. High intensity in the
      putamen on T1-weighted MR images in the present case might represent multiple
      petechial hemorrhages which occurred in association with metabolic disorders
      including nonketotic hyperglycemia.

PMID- 8156713
TI  - [A case of paradoxical cerebral embolism through a patent foramen ovale diagnosed
      by necropsy].
AB  - A 62-year-old man was admitted to our hospital for disturbed consciousness and
      left-side motor sensory deficit. His blood pressure was 142/100 mmHg and an
      electrocardiogram was normal. CT of the brain revealed a low density area in the
      distribution of the right middle cerebral artery (MCA). Cerebral angiography
      demonstrated occlusion of the right internal carotid artery and an embolus. We
      diagnosed cerebral embolism, but we could not detect source of embolism. His
      condition deteriorated rapidly, and he died four days later. At necropsy, an
      elongated piece of thrombus 10 cm in length was lodged in a patent foramen ovale
      lying in each atrium. No other thrombus was seen in the heart, the myocardium and
      coronary arteries were normal. Both main pulmonary arteries contained thrombus.
      The lungs showed edema and congestion. There was no thrombus of both common iliac
      veins. The right internal carotid artery was occluded at its bifurcation by
      embolus, distal to which the cavernous segment was 7 cm filled with clot. We
      reported a rare paradoxical cerebral embolism through a patent foramen ovale
      diagnosed by necropsy. If no left-sided circulatory source can be demonstrated,
      the possibility of a paradoxical embolism should be considered.

PMID- 8156714
TI  - [Reflex sympathetic dystrophy secondary to lumbar disk herniation].
AB  - A 26-year-old woman noticed discoloration and swelling of the left foot after
      standing or sitting for a long period of time. Four months later, she developed
      dysesthesia in the left leg and foot and extreme tenderness of the left foot;
      developed subsequently claudication. At age 15, the patient had severe low back
      pain for 1 year and had been diagnosed as having lumbar disk herniation.
      Recurrent disk herniation was suspected, although myelogram and postmyelogram CT
      scan reportedly were nondiagnostic. The patient was admitted to our hospital 6
      months following the onset of dysesthesia. Physical examination revealed weakness
      and atrophy of the entire left lower extremity, allodynia of the left foot, and
      dysesthesia in the left L5 myotomes. Hypertrichosis was obvious, and the left
      foot was cool on touch. Roentgenography of the left lower extremity revealed
      patchy osteoporosis of the distal epiphyse of the left tibia and fibula and in
      some of tarsal bones. Intravenous administration of phentolamine reduced
      tenderness, which was highly suggestive of reflex sympathetic dystrophy (RSD). A
      repeat CT scan revealed extraforaminal, left-sided disk herniation at L4/5. We
      diagnosed RSD secondary to L5 radiculopathy and performed a left L2, 3 lumbar
      sympathetic block. Allodynia was relieved, and the patient was able to walk
      without claudication. Reports of RSD secondary to lumbar disk herniation are
      rare. In one case, transient lumbar sympathetic block was effective in
      alleviating symptoms of RSD, although, required surgery. Our patient was more
      severely disabled than patients in other reports, yet, lumbar sympathetic block
      still was effective.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156715
TI  - [Juvenile muscular atrophy of the bilateral upper limbs associated with peculiar
      transformation of the dural tube induced by neck flexion].
AB  - We described an 18-year-old man with slowly progressive muscular atrophy in upper
      limbs on both sides. Regarding muscular atrophy, sensory disturbances in both
      palms were disproportionally very mild. Electrophysiological study suggested
      involvement of anterior horn restricted to the cervical cord, which resembled
      juvenile muscular atrophy of unilateral upper limb (Hirayama's disease). This
      patient, however, was unique in that the atrophy was bilateral and wider
      distribution of a lesion from C5 to T1 segments unlike Hirayama's disease.
      Neuroradiological findings in neutral position of the neck showed no
      abnormalities, but in flexion there was a characteristic change of the cervical
      cord and the posterior wall of dural canal. On myelography in flexion, anterior
      posterior diameter of the middle and lower cervical dural canal decreased
      presumably due to an anterior shift of the dorsal part of dura mater. CT
      myelography in neck flexion showed characteristic folding of the dorsal part of
      dura mater whose median portion seemed to intrude anteriorly and consequently
      concave the spinal cord. Anterior shift of the dorsal part of dura mater is known
      to occur in Hirayama's disease, but the folding is a peculiar finding in this
      patient. After laminectomy and laminoplasty of vertebrae from C3 to C7, his
      symptoms improved a little. On palpating the dorsal surface of dural canal, its
      median portion was harder than the lateral portion. A small fraction of the dura
      mater which was removed from hard median portion was thick, but showed no
      histological abnormalities. In normal functioning anatomy the dural canal is
      lengthened more posteriorly than anteriorly with neck flexion.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8156716
TI  - [Persistent isolated abducens nerve palsy from pontine infarction confirmed by
      gadolinium-DTPA enhanced MRI].
AB  - An 80-year-old man had left isolated abducens nerve palsy after repeated
      conjugate deviation to the right without any other findings. MRI demonstrated no
      abnormal lesion of T2-weighted images, while left paramedian tegmentum pontis was
      enhanced as responsible lesion by gadolinium (Gd)-DTPA on the 13th hospital day
      when Foville syndrome lasted. On the 33rd hospital day when isolated abducens
      nerve palsy lasted, however, this lesion was not detected with Gd enhanced
      images. The diagnosis of abducens nerve palsy caused by pontine infarction was
      obtained. Our patient had a lesion involving the left PPRF and ipsilateral
      abducens nerve. We concluded that the complete damage of left abducens motoneuron
      may cause isolated abducens nerve palsy lasting more than one year after Foville
      syndrome due to the dysfunction of left PPRF. To our knowledge, this is the first
      report of the persistent isolated abducens nerve palsy resulting from a pontine
      miniature ischemic lesion speculated by Gd enhanced MRI.

PMID- 8156717
TI  - [A 46-year-old woman with myasthenia gravis associated with macromastia,
      erythroderma and hypogeusia].
AB  - A 46-year-old woman developed blepharoptosis, diplopia and hypogeusia in 1984,
      and was diagnosed as having myasthenia gravis and malignant thymoma. Her symptoms
      improved by thymectomy and oral prednisolone administration. In 1988 she
      complained of breast pain and swelling during menstruation. In 1990 her breast
      was enlarged to the size of an adult head, and she developed erythroderma and
      hypogeusia. She was admitted to Nagasaki University Hospital in August, 1990. On
      admission, erythema was seen in the whole body especially in the face, anterior
      chest, abdomen and the thigh. Her breast was the size of an adult head. Muscle
      strength was weak, and ocular movement was limited. She had blepharoptosis.
      Papillae of the tongue were atrophic. Endoclinological investigations revealed an
      elevation of PRL to 14.6 ng/ml (normal < 10), antibodies to the acetylcholine
      receptor to 118.0 nM (normal < 0.5). In TRH stimulation test the response of PRL
      was amplified. Four intrathoracic masses suspected of recurrence of malignant
      thymoma were seen in CT. Her macromastia depended upon the amount of PRL, and was
      reduced by bromocriptine. Erythroderma and hypogeusia were relieved by
      plasmaphersis. Therefore autoimmune mechanism may be related to these symptoms.

PMID- 8156718
TI  - [A case of subacute sclerosing panencephalitis treated with intraventricular
      interferon--the side effects of interferon-alpha to the central nervous system].
AB  - A patient with subacute sclerosing panencephalitis (SSPE) was treated with an
      intraventricular alpha interferon (IFN-alpha) through an Ommaya reservoir. A 17
      year-old boy, who had a history of measles exposure at age 1, showed
      forgetfulness, difficulties in calculation, reading and writing. Two months later
      he developed generalized convulsions and myoclonic spasms. He was admitted to the
      National Saigata Hospital in May 20, 1992. On admission, anti-measles antibody
      titer in the CSF was 1:16 by complement-fixation method. His EEG revealed a
      periodic synchronous discharge. Therefore, the diagnosis of SSPE was confirmed.
      An Ommaya reservoir was implanted on July 7, 1992, and an intraventricular
      administration of INF-alpha was begun after two weeks. The dose of INF-alpha was
      gradually increased from 1.0 x 10(6) IU/m2 to 2.0 x 10(6) IU/m2 twice a week.
      Fever, vomiting and anorexia were developed when the INF-alpha injection was
      first started. When he received a total dose of 8.0 x 10(6) IU, he became bed
      ridden for remarkable lethargy. The lethargy was continued for about 10 days
      despite the therapy was interrupted, and then he gradually became alert. The
      frequency of myoclonus became more frequent and mentality got worse, so the
      treatment with INF-alpha was tried again in decreasing the dose to 1.0 x 10(6)
      IU/m2 twice a week. However, be became drowsy again after he received a total of
      7.5 x 10(6) IU. With intramuscular or intravenous administrations of the high
      doses of INF-alpha (> or = 1.0 x 10(7) IU), significant neurological
      abnormalities were reported to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156719
TI  - [Acquired unilateral blepharoptosis by wearing contact-lenses in young adult
      women].
AB  - Four young unmarried women developed unilateral non-fluctuating blepharoptosis by
      wearing contact-lenses. Past and family histories were unremarkable.
      Blepharoptosis insidiously occurred within a few years after wearing lenses.
      Contralateral lid was quite normal. No abnormalities was observed in pupils,
      extraocular muscles, ocular positioning and other systems. So far recognized
      causes of blepharoptosis were ruled out through extensive clinical and laboratory
      observations. Improvement was insufficient even after wearing lenses off.
      Pathogenesis is probably due to repeated minor trauma to the levator palpebral
      muscle and its tendon secondary to frequent wearing on/off contact-lenses.

PMID- 8156720
TI  - [Pseudoathetosis and deep sensation].

PMID- 8156721
TI  - Effect of cotton-tipped swab use on ear-wax occlusion.
AB  - We studied parents' and patients' approach to earwax (cerumen) removal, patients'
      level of cerumen occlusion, and the association between the use of cotton-tipped
      swabs (CTS) and cerumen occlusion. Six hundred fifty-one consecutive patients
      from the general pediatric practice of the Cleveland Clinic aged 2 weeks to 20
      years (57% males) answered a questionnaire with their parents' help. Of the 651,
      401 (62%) had used CTS during the 2 months before the study. Examiners unaware of
      the questionnaire results found that 46 (7%) of both right and left ear canals
      were at least 75% occluded by cerumen. Cerumen occlusion of at least 75% was
      associated with CTS use on the left side (P = .02), but not on the right side (P
      = .27). We conclude that cotton-tipped swab use may be associated with cerumen
      accumulation.

PMID- 8156722
TI  - Association of hyperpyrexia with serious disease in children.
AB  - In a prospective study over 7 years, 105 consecutive pediatric patients with
      hyperpyrexia (temperature > or = 41.1 degrees C [106 degrees F]) were evaluated
      to determine the incidence, sensitive indicators, and types of illnesses
      encountered. The incidence of hyperpyrexia in a large urban pediatric emergency
      department was 0.36 per 1,000 visits or approximately one in 2,759 visits. In
      patients with temperature > or = 41.1 degrees C, 65 (61.9%) had a serious
      illness. Pneumonia (33 lobar, three interstitial, two clinical) was the most
      common diagnosis (36.2%), followed by probable viral illness in 20 (19.0%) of the
      patients. Bacteremia (6.7%) and bacterial meningitis (5.7%) were less commonly
      found. Four (3.8%) patients died. The admission rate was 62.9%. Eighteen patients
      (17.1%) also had seizures. Sensitive indicators to help distinguish those with
      serious illness, with the exception of clinical appearance, were not found.
      Pneumonia is commonly found in children with hyperpyrexia. Temperature > or =
      41.1 degrees C was associated with a high rate of serious disease.

PMID- 8156723
TI  - Severe hemolytic anemia associated with vitamin E deficiency in infants with
      cystic fibrosis. Implications for neonatal screening.
AB  - Three infants are described with cystic fibrosis (CF) and malnutrition leading to
      severe anemia beginning as early as 6 weeks of age. Laboratory studies
      demonstrated high reticulocyte counts, negative Coombs' tests, abnormal peroxide
      hemolysis test results, and biochemical evidence of vitamin E deficiency. Oral
      administration of alpha-tocopherol resulted in rapid correction of the in vitro
      hemolysis and improvement of in vivo hematologic indices. Investigation of these
      patients supports the conclusion that the hemolytic anemia of infancy in CF is
      caused by vitamin E deficiency and should be treated promptly with 50 IU/day of
      vitamin E. Because two of the three patients were identified in a CF
      screening/surveillance program, we can estimate that the frequency of clinically
      significant anemia in CF infants is 4%. Our observations demonstrate a potential
      advantage of CF neonatal screening for individual patients susceptible to vitamin
      E-deficient hemolytic anemia and suggest that confirmatory follow-up diagnostic
      studies, such as sweat tests, should be performed by 4 to 6 weeks of age.

PMID- 8156724
TI  - Sexually transmitted diseases.
AB  - Adolescents have the highest rate of sexually transmitted disease (STD) of any
      sexually active age group. This article reviews the biological, psychological,
      and social factors that place adolescents at increased risk for STDs. The major
      STDs are reviewed, including epidemiology, clinical presentation, methods of
      diagnosis, and treatment modalities. In addition, major sequelae of STDs-
      including pelvic inflammatory disease, perihepatitis, Reiter's syndrome, and
      disseminated gonorrhea infection--are discussed.

PMID- 8156725
TI  - Genital bleeding. Two uncommon causes in patients referred to a sexual abuse
      clinic.

PMID- 8156726
TI  - Severe hepatotoxicity, acute renal failure, and pancytopenia in a young child
      after repeated acetaminophen overdosing.

PMID- 8156727
TI  - Symbolic scarring and tattooing. Unusual manifestations of child abuse.

PMID- 8156728
TI  - Daytime urinary frequency in children.

PMID- 8156729
TI  - Advances in the management of precocious puberty.

PMID- 8156730
TI  - Effect of position and support on oral-motor skills of a child with
      bronchopulmonary dysplasia.
AB  - The effects of position (upright vs reclining) and support (held vs chair) on the
      development and maintenance of feeding behavior were examined in a child with
      bronchopulmonary dysplasia and gastroesophageal reflux. A reclining position
      initially facilitated acceptance and swallowing with relatively rapid
      generalization to an upright position. Oral-motor skills did not differ across
      levels of support. Practice of emerging motor skills preceded increases in
      vomiting, as well as episodes of respiratory distress. This study illustrates a
      methodology that can be employed to elucidate complex interrelationships among
      oral-motor skills, gross motor skills and functioning, and symptoms of
      gastroesophageal reflux.

PMID- 8156731
TI  - Effect of recombinant human growth hormone on cellular sodium metabolism.
AB  - 1. The effect of treatment with recombinant human growth hormone on urinary
      sodium excretion, total body water, the renin-angiotensin system and erythrocyte
      sodium metabolism was investigated in 16 adults with growth hormone deficiency.
      2. Total body water was determined by isotopic dilution, and erythrocyte
      electrolyte contents were analysed using flame photometry. The rate of sodium
      influx and the efflux rate constant of sodium were calculated from values of 22Na
      in erythrocytes in vitro. 3. One week of treatment with recombinant human growth
      hormone caused a decrease in urinary sodium excretion in 9/10 patients and an
      increase in erythrocyte sodium content. Total body water, plasma renin activity,
      angiotensin II concentration and transmembrane sodium transport were unaltered.
      4. Six months of treatment with recombinant human growth hormone caused
      significant increases in total body water, erythrocyte sodium content and sodium
      transmembrane influx. Plasma renin activity tended to increase, whereas blood
      pressure and serum sodium and potassium concentrations remained unchanged. After
      6 months on recombinant human growth hormone total body water showed a
      significant negative correlation with plasma renin activity. 5. The enhanced
      erythrocyte sodium transport, if this reflects what happens in the renal tubular
      cell, combined with a decrease in urinary sodium excretion, during treatment with
      recombinant human growth hormone could indicate an increase in tubular sodium
      reabsorption induced by the hormone. An increased plasma renin activity
      associated with the lack of blood pressure rise would reinforce sodium and water
      retention.

PMID- 8156732
TI  - Abnormal erythrocyte and renal frusemide-sensitive sodium transport in idiopathic
      calcium nephrolithiasis.
AB  - 1. Anomalous transmembrane anion transport has been observed in erythrocytes of
      patients with idiopathic calcium nephrolithiasis. 2. To verify whether cation
      transport is also abnormal, we investigated the frusemide-sensitive Na+ efflux
      from Na(+)-loaded erythrocytes and the natriuretic response to acute intravenous
      frusemide administration in calcium oxalate renal stone formers. 3. Frusemide
      administration induced a statistically significant smaller increase in the
      fractional excretion of Na+ in patients than in control subjects. Abnormal
      kinetic properties of erythrocyte Na(+)-K(+)-2Cl- cotransport were observed in
      approximately 60% of stone formers. The Km for Na+ of Na(+)-K(+)-2Cl- co
      transport correlated with urinary Ca2+ excretion. 4. The abnormal kinetic
      properties of Na(+)-K(+)-2Cl- co-transport may be relevant for stone formation,
      hampering renal Ca2+ reabsorption in the distal nephron and determining critical
      physicochemical conditions for calcium/oxalate crystallization.

PMID- 8156733
TI  - Involvement of nitric oxide in the vasodilatory response to parathyroid hormone
      related peptide in the isolated rabbit kidney.
AB  - 1. The present study was designed to explore the role of NO derived from L
      arginine in the vasodilatory response to synthetic human parathyroid hormone
      related peptide-(1-34) in the isolated rabbit kidney perfused in the presence of
      indomethacin (10 mumol/l) and preconstricted with noradrenaline (7.2 nmol/min).
      2. Under control conditions, bolus administrations of acetylcholine (10 mumol/l),
      an NO-dependent renal vasodilator, verapamil (0.1 mmol/l), an NO-independent
      renal vasodilator, and parathyroid hormone-related peptide (87 nmol/l) decreased
      the preconstriction pressure, by 31%, 71% and 43%, respectively. 3. Bolus
      administration of 100 mumol/l NG-nitro-L-arginine-methyl ester caused a 20%
      increment in the perfusion pressure of the noradrenaline-preconstricted kidney.
      NG-nitro-L-arginine methyl ester inhibited the vasodilatory effect of
      acetylcholine and parathyroid hormone-related peptide, by 68% and 44%,
      respectively, but did not alter the verapamil-induced vasodilatation. 4. Unlike L
      arginine, the bolus administration of 1 mumol/l of a mono-substituted L-arginine
      derivative, N-alpha-benzoyl-L-arginine ethyl ester, durable decreased the
      noradrenaline/NG-nitro-L-arginine methyl ester-induced preconstriction by 57%. 5.
      Both L-arginine and N-alpha-benzoyl-L-arginine ethyl ester effectively reversed
      the inhibition induced by NG-nitro-L-arginine methyl ester on the vasodilatation
      elicited by acetylcholine and parathyroid hormone-related peptide. 6. In
      conclusion, the formation of NO from L-arginine contributes a substantial part to
      the vasodilatory action of parathyroid hormone-related peptide. Therefore,
      parathyroid hormone-related peptide appears to have a place among the renal
      haemodynamically active substances, whose vasodilatory actions are tuned by NO.

PMID- 8156734
TI  - Albumin excretory rate in normal and hypertensive pregnancy.
AB  - 1. The purpose of this study was to determine whether the 24 h urinary albumin
      excretory rate was increased in the third trimester of normal pregnancy or in
      pregnant women with hypertension who had 24 h urinary total protein excretion
      within the normal range. 2. Twenty-four hour urinary creatinine and albumin
      excretions were determined prospectively in 26 non-pregnant and 115 pregnant
      women in their third trimester (40 in normal pregnancy, 38 with mild pre
      eclampsia, 20 with severe pre-eclampsia, 17 with essential hypertension) in whom
      urinary total protein excretion was normal. Both the urinary albumin excretion
      rate and the urinary albumin/creatinine ratio were compared among the groups. The
      clearance of albumin relative to that of creatinine was also calculated in the
      hypertensive women and in 14 of the non-pregnant women and nine of the normal
      pregnant women. 3. The twenty-four hour urinary albumin excretion rate was
      similar in non-pregnant [8(5-10) mg/day; median (interquartile range)] and normal
      pregnant [7(6-10) mg/day] women. Women with essential hypertension [6(4-16)
      mg/day] and mild pre-eclampsia [7(4-10) mg/day] had a urinary albumin excretion
      rate similar to that of normal pregnant women. Women with severe pre-eclampsia
      had an urinary albumin excretion rate increased [13(7-32) mg/day] compared with
      other groups (P < 0.05). The clearance of albumin relative to that of creatinine
      was elevated significantly only in women with severe pre-eclampsia compared with
      normal pregnant women (0.00054 versus 0.00012; P < 0.05). Blood pressures were
      similar among all hypertensive groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156735
TI  - Contractile dysfunction in the diabetic-rat heart is an intrinsic abnormality of
      the cardiac myocyte.
AB  - 1. In order to clarify whether the myocardial dysfunction observed in diabetic
      rat hearts is an intrinsic property of the myocytes or not, we investigated
      cardiac function and myocyte contractile function in diabetic rats 5 weeks after
      the injection of streptozotocin. 2. Maximal and minimal dP/dt and time constant
      of isovolumic pressure fall were measured using a micromanometer in diabetic and
      age-matched control rats. 3. Isolated myocytes were enzymically obtained from
      each rat heart and were stimulated at 1 Hz (37 degrees C) in a buffer containing
      1.5 mmol/l Ca2+. The images of myocyte contractions were recorded by a video
      system. Normalized maximal velocity of shortening (maximal velocity of cell
      shortening/resting cell length; s-1), normalized maximal velocity of
      relengthening (maximal velocity of cell relengthening/resting cell length; s-1)
      and extent of shortening [(twitch amplitude/resting cell length) x 100; %] were
      analysed by a digitalized computer as contractile functions of the myocyte. 4.
      The maximal and minimal dP/dt in diabetic rats (7876, 5341 mmHg/s) were
      significantly lower than those in control rats (9349, 7876 mmHg/s). The time
      constant of isovolumic pressure fall in diabetic rats (12.7 ms) was significantly
      greater than that in control rats (8.6 ms). Moreover, the normalized maximal
      velocity of shortening, normalized maximal velocity of relengthening and extent
      of shortening in myocytes from diabetic rats (1.40 s-1, 1.38 s-1, 9.5%) were
      significantly lower than those in myocytes from control rats (1.64 s-1, 1.60 s-1,
      11.8%). 5. These results suggest that contractile impairment in this diabetic-rat
      heart model is mainly due to an intrinsic abnormality of the cardiac myocytes.

PMID- 8156736
TI  - Platelet membrane microviscosity in Sabra rats with early salt hypertension.
AB  - 1. To investigate the possibility that arterial hypertension is associated with
      changes in the physicochemical properties of cell membranes, we have studied the
      effects of dietary salt loading on platelet membrane microviscosity in
      hypertension-prone and -resistant Sabra rats. 2. Sixteen hypertension-prone and
      14 hypertension-resistant Sabra rats were submitted to either a low-salt (0.25%
      NaCl) or a high-salt (4% NaCl) diet for 3-4 weeks. Platelet membrane anisotropy
      was determined, in the presence and absence of extracellular Na+, using two
      fluorescent probes, diphenylhexatriene and trimethylamino-diphenylhexatriene,
      inserted in different areas of the cell membranes. 3. A decrease in
      diphenylhexatriene anisotropy was demonstrated when platelets of hypertension
      prone (but not hypertension-resistant) Sabra rats were suspended in a Na(+)-free
      medium. This alteration in membrane dynamic properties is localized within the
      hydrophobic core of the platelet membranes and is independent of salt intake. It
      reflects an abnormal fluidizing effect of extracellular Na+ removal. 4. Platelets
      of hypertension-prone and hypertension-resistant Sabra rats did not differ
      significantly in trimethylamino-diphenylhexatriene fluorescence anisotropy,
      irrespective of the incubation media used. Extracellular Na+ removal caused an
      increase in trimethylamino-diphenylhexatriene fluorescence anisotropy in all
      groups, the change being greatest in salt-loaded rats. 5. This study indicates
      that platelet membrane microviscosity is specifically altered in the hypertension
      prone Sabra rat irrespective of salt intake. This raises the question of the
      relation of this inherited defect with the susceptibility of this strain to
      dietary salt loading.

PMID- 8156737
TI  - Plasma levels of 5-hydroxytryptamine during sympathetic stimulation and in
      Raynaud's phenomenon.
AB  - 1. The involvement of plasma 5-hydroxytryptamine in normal subjects during
      sympathetic stimulation and in patients with Raynaud's phenomenon was studied. 2.
      Arterial and venous plasma levels of 5-hydroxytryptamine were measured in normal
      subjects in a warm room, during reflex sympathetic stimulation by body cooling
      and during intra-arterial infusions of tyramine. Normal subjects (n = 19) had
      significantly higher levels of 5-hydroxytryptamine in venous plasma [mean 1.42
      (SEM 0.23) ng/ml] than in arterial plasma [0.67 (0.12) ng/ml; P < 0.01]. Body
      cooling (n = 10) or tyramine infusion (n = 8) did not increase venous levels of 5
      hydroxytryptamine despite significant decreases in blood flow and increases in
      vascular resistance. 3. Venous plasma levels of 5-hydroxytryptamine were also
      determined in patients with primary Raynaud's phenomenon (n = 12) or secondary
      Raynaud's phenomenon due to scleroderma (n = 11). Patients with primary or
      secondary Raynaud's phenomenon did not have significantly higher venous plasma
      levels of 5-hydroxytryptamine than normal subjects, even during vasospastic
      attacks (n = 3). 4. It is concluded that either 5-hydroxytryptamine is not
      involved in sympathetic nerve vasoconstriction or in Raynaud's phenomenon, or 5
      hydroxytryptamine released in the microcirculation is largely taken up or
      metabolized by endothelial cells or platelets.

PMID- 8156738
TI  - Atrial natriuretic factor potentiates the human forearm vasoconstrictor response
      to sympathetic stimulation.
AB  - 1. Atrial natriuretic factor has been suggested to affect human sympathetic
      nervous system activity. The interaction between atrial natriuretic factor and
      the sympathetic nervous system has not been fully elucidated yet, but may occur
      at different sites. We studied this modulator effect at the level of the forearm
      vascular bed: the forearm vasoconstrictor response was examined after alpha
      adrenergic sympathetic stimulation in healthy subjects during the locoregional
      administration of atrial natriuretic factor, sodium nitroprusside and placebo. As
      a sympathetic stimulation test, the technique of the lower body negative pressure
      (-20 mmHg) was used. 2. Lower body negative pressure increased the forearm
      vascular resistance by +37 +/- 8% during concomitant intra-arterial infusion of
      placebo (n = 10). During a predilator state achieved by infusion of atrial
      natriuretic factor (10 ng min-1 100 ml-1 forearm volume) into the brachial
      artery, lower body negative pressure subsequently induced a forearm
      vasoconstrictor response of +153 +/- 22% (P < 0.05 versus placebo), whereas this
      was +64 +/- 14% when predilatation was achieved by infusion of an equipotent
      vasodilator dose of sodium nitroprusside (P > 0.1 versus placebo; P < 0.05 versus
      atrial natriuretic factor). The potentiation of the forearm vasoconstrictor
      response to lower body negative pressure by atrial natriuretic factor only
      occurred in the experimental and not in the contralateral arm. According to
      calculations on simultaneously sampled arterial and venous plasma catecholamine
      concentrations, the augmented forearm vasoconstrictor response seemed not to be
      caused by an increased release of noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156739
TI  - Ethanol decreases nocturnal plasma levels of atrial natriuretic peptide (ANP 99
      126) but not the N-terminal fragment of pro-atrial natriuretic peptide (ANP 1-98)
      in man.
AB  - 1. The aim of this study was to elucidate the role of atrial natriuretic peptides
      in the regulation of water and electrolyte balance after alcohol intake. To this
      end we measured the plasma concentrations of ethanol, atrial natriuretic peptide
      99-126 and the N-terminal fragment of pro-atrial natriuretic peptide (atrial
      natriuretic peptide 1-98), serum osmolality and serum sodium concentration, and
      urine output, urine osmolality and urinary sodium excretion for 12 h after
      administration of ethanol (0, 0.5 and 1.0 g body weight/kg) and placebo drinks to
      nine healthy subjects according to a double-blind cross-over design. 2. Intake of
      ethanol (at 19.00-19.45 hours) inhibited the nocturnal increase in the plasma
      atrial natriuretic peptide 99-126 level dose-dependently (P < 0.05), but had no
      effect on the plasma atrial natriuretic peptide 1-98 level. Serum osmolality and
      serum sodium concentration were elevated dose-dependently for 2-5 h after the
      ethanol intake. Urine volume increased after the higher ethanol dose (net loss of
      0.6 litre of water). 3. Since the plasma atrial natriuretic peptide 1-98 level
      was not changed after ethanol intake, we propose that the alcohol-induced
      inhibition of the nocturnal rise in the plasma atrial natriuretic peptide 99-126
      level is not caused by an inhibition of release, but may rather reflect an
      increased peripheral elimination of atrial natriuretic peptide 99-126.

PMID- 8156740
TI  - Role of cardiorespiratory abnormalities, smoking and dive characteristics in the
      manifestations of neurological decompression illness.
AB  - 1. Blind analysis of contrast echocardiograms to detect intracardiac shunts,
      blind analysis of lung function tests for evidence of small airways disease,
      smoking history and dive characteristics were examined in an attempt to explain
      neurological symptoms that occurred within 5 min of surfacing from unprovocative
      dives. 2. Pulmonary abnormalities were significantly more frequent in those
      divers without intracardiac shunts (50%) than in those with shunts (0%). Smoking
      was more common in those divers without shunts (55% versus 15%), although this
      just failed to reach conventional significance levels. Divers without shunts
      experienced cerebral rather than spinal symptoms after significantly shallower
      dives with lower tissue nitrogen loads. Depths of dives, tissue nitrogen loads
      and clinical manifestations in those divers without shunts were similar to the
      findings in divers who had symptoms after rapid ascents. Despite conservative
      dive profiles, clinical manifestations in divers with shunts resembled those
      observed after missed decompression stops. 3. The findings suggest that occult
      lung disease, and probably smoking, increase the risk of neurological symptoms,
      even after unprovocative dives, and the similarity of the dive profiles and
      clinical manifestations to cases with rapid ascents suggest that pulmonary
      barotrauma and arterial gas embolism are responsible. In divers with intracardiac
      shunts the different dive profiles and clinical manifestations imply that there
      is another mechanism, involving different tissue and bubble nitrogen kinetics
      resulting in venous gas liberation and peripheral amplification in embolized
      tissues, rather than paradoxical embolism per se.

PMID- 8156741
TI  - Arthrogenic quadriceps inhibition and rehabilitation of patients with extensive
      traumatic knee injuries.
AB  - 1. The relationship between joint damage, quadriceps weakness and arthrogenic
      muscle inhibition was investigated in eight patients who had sustained extensive
      traumatic knee injury. Isometric and isokinetic quadriceps and hamstring
      voluntary strength, and quadriceps arthrogenic muscle inhibition during isometric
      contractions, were measured before and after 4 weeks (approximately 100 h) of
      intensive rehabilitation. 2. Compared with the uninjured leg, before
      rehabilitation the injured leg had larger amounts of quadriceps arthrogenic
      muscle inhibition (P < 0.025), quadriceps (P < 0.0001) and hamstring (P < 0.0001)
      weakness and severe functional joint instability. There was a negative
      correlation between the amount of arthrogenic muscle inhibition and quadriceps
      voluntary contraction force (P < 0.025). 3. After rehabilitation in the injured
      leg there were small hamstring strength increases (P < 0.05-0.025), but no
      overall significant quadricep strength increase. Arthrogenic muscle inhibition
      was statistically unchanged. Severe functional joint instability was still
      reported by all patients. 4. Previous studies have shown that minimal joint
      damage evokes relatively less arthrogenic muscle inhibition that does not impede
      rehabilitation. These data indicate that greater joint damage is associated with
      greater arthrogenic muscle inhibition, quadriceps weakness and joint instability.
      Furthermore, intensive rehabilitation had little affect on either quadriceps
      arthrogenic muscle inhibition or atrophy.

PMID- 8156742
TI  - Alpha- and beta-cell function in obese Zucker (fa/fa) rats: a study with the
      isolated perfused pancreas.
AB  - 1. The effects of various stimuli, including changes in glucose concentration,
      arginine, tyramine and noradrenaline, on insulin and glucagon secretion were
      investigated using isolated perfused pancreata of obese and lean male Zucker rats
      at 12 months of age. 2. In Zucker fatty rats, the insulin secretion rate was
      significantly (P < 0.01) higher than that of lean rats at all glucose
      concentrations tested (8.3, 16.7 and 1.4 mmol/l). However, the integrated insulin
      secretory response to raising the glucose concentration from 8.3 to 16.7 mmol/l
      was almost absent in these rats. The glucagon secretion rates were significantly
      lower at 8.3 and 1.4 mmol/l glucose (P < 0.001 for both), and in responses to 10
      micrograms/ml tyramine and 0.1 mumol/l noradrenaline (P < 0.05 for both), in
      Zucker fatty rats. Integrated insulin and glucagon responses to 10 mmol/l
      arginine were identical in the two groups. 3. Histopathological and
      immunochemical studies revealed hyperplasia of beta-cells and scattered alpha
      cells in the enlarged islets of Zucker fatty rats. 4. These results suggest that,
      in Zucker fatty rats, the decreased glucagon secretion in the isolated perfused
      pancreas is attributable to changes in the environment of alpha-cells and/or the
      inhibitory effects of hypersecreted insulin.

PMID- 8156743
TI  - Assessment of insulin sensitivity in man: a comparison of minimal model- and
      euglycaemic clamp-derived measures in health and heart failure.
AB  - 1. Simplified protocols for the measurement of insulin resistance will facilitate
      studies of this potentially important variable. 2. Using the euglycaemic clamp as
      the reference technique, we have assessed the validity of the insulin sensitivity
      index (inversely related to insulin resistance) obtained using a high-dose (500
      mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling
      schedule and analysis using the minimal model of glucose disappearance. The two
      methods were compared in 10 clinically normal subjects and five patients with
      severe heart failure secondary to coronary heart disease. 3. The insulin
      sensitivity index of the minimal model was compared with four clamp-derived
      measures. Correlation coefficients of 0.72-0.92 (P < 0.01-P < 0.001) were
      obtained between the two methods over a wide range of insulin sensitivity [model
      values 1.03-14.63 min-1/(pmol/l) x 10(-5)]. Patients with heart failure had the
      lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous
      glucose tolerance test with minimal model analysis is a straightforward and
      economical clinical procedure and provides a valid measure of insulin
      sensitivity, in health and disease.

PMID- 8156744
TI  - Lipoprotein profiles in a family with two mutants of apolipoprotein E: possible
      association with hypertriglyceridaemia but not with dysbetalipoproteinaemia.
AB  - 1. The plasma lipoprotein profiles of eight members of a Dutch pedigree spanning
      three generations where two rare apolipoprotein E mutants, APOE*3(Cys-112-->Arg;
      Arg-251-->Gly) and APOE*2(Val-236-->Glu), segregate were analysed to determine
      whether the APOE mutants were associated with dyslipidaemia. 2. The proband, a 51
      year-old Caucasian male, was a carrier of APOE*3(Cys-112-->Arg; Arg-251-->Gly)
      and his spouse was a carrier of APOE*2(Val-236-->Glu). Four other family members
      were carriers of one or both of the mutant APOE genes. 3. The plasma cholesterol
      and triacylglycerol concentrations were markedly elevated in the proband and were
      classified as type IV hyperlipoproteinaemia. The plasma triacylglycerol
      concentration was moderately increased in a sister, who was a carrier of
      APOE*3(Cys-112-->Arg; Arg-251-->Gly), and in the son, who was a compound
      heterozygote for both mutant APOE alleles. Normal plasma lipid levels were
      observed in all other family members. In the plasma samples of the proband and
      his family members beta-very-low-density lipoprotein was not detectable and the
      molar ratio of very-low-density lipoprotein-cholesterol to very-low-density
      lipoprotein-triacylglycerol was less than 0.9. The concentration of intermediate
      density lipoprotein was within normal limits. 4. None of the family members
      carrying APOE*3-(Cys-112-->Arg; Arg-251-->Gly) and/or APOE*2(Val-236-->Glu)
      exhibited lipoprotein abnormalities characteristic of familial
      dysbetalipoproteinaemia, although three family members carrying APOE*3-(Cys-112-
      >Arg; Arg-251-->Gly) showed hypertriglyceridaemia.

PMID- 8156745
TI  - Production of interleukin-6 and tumour necrosis factor-alpha in vitro is reduced
      in whole blood of severely malnourished children.
AB  - 1. Cytokine production in vitro was assessed in 16 malnourished children, before
      and after nutritional recovery. 2. Tumour necrosis factor-alpha and interleukin-6
      were measured in whole blood after lipopolysaccharide stimulation. 3. The total
      amount of both cytokines was significantly less after 24 h incubation among
      malnourished children when compared with the same children after nutritional
      rehabilitation. 4. Cytokine production in vitro is impaired in severely
      malnourished children.

PMID- 8156746
TI  - Do thiazides reduce intestinal oxalate absorption?: a study in vitro using rabbit
      colon.
AB  - 1. The purpose of the present study was to examine the effects of various
      diuretics on intestinal oxalate transport. Transmural oxalate fluxes were
      measured across isolated, short-circuited tissue segments removed from rabbits
      and placed in Ussing chambers. 2. The net absorptive flux of oxalate across the
      distal colon was significantly reduced in the presence of trichlormethiazide at
      10(-4) mol/l. In contrast, this diuretic had no effect on oxalate transport in
      the other intestinal segments examined. Several of the thiazide diuretics tested
      had some inhibitory effect on colonic oxalate absorption, but at higher
      concentrations of 10(-3) mol/l or 10(-2) mol/l. 3. We conclude that the
      previously reported hypooxaluric effects of hydrochlorothiazide and
      chlorthalidone are most likely not the result of an exclusive or primary effect
      on intestinal oxalate transport. It is suggested that the reduction in colonic
      oxalate absorption that was observed with the thiazides probably involves the
      transport system responsible for oxalate efflux across the basolateral membrane
      of the colonocyte.

PMID- 8156747
TI  - OoClamp: an IBM-compatible software system for electrophysiologic receptor
      studies in Xenopus oocytes.
AB  - A software system for IBM-compatible microcomputers running MS-DOS or Microsoft
      Windows 3.1 is described which facilitates the acquisition, analysis and storage
      of data from electrophysiologic studies of receptors expressed in Xenopus laevis
      oocytes. The system is designed to provide standardization of test conditions,
      automation of all routine functions, rapid, on-line analysis of data, and self
      documentation and compact storage of data files. All system settings are
      optimized for use with the Xenopus expression system, but can be adapted to other
      large cells. An example application, expression of muscarinic acetylcholine
      receptors in Xenopus oocytes, is described.

PMID- 8156748
TI  - Pre-compiling medical logic modules into C++ in building medical decision support
      systems.
AB  - Development of medical knowledge bases is a time-consuming process, and no single
      medical institution can develop medical knowledge bases covering all areas of
      medicine. The use of medical knowledge representation standards such as the Arden
      Syntax is an attempt to enhance the writability and readability of computer
      stored knowledge and facilitate transfer and sharing among institutions. A method
      for the realisation of decision support systems based on knowledge formulated
      according to the Arden Syntax is presented. An essential tool in this process is
      a medical logic module (MLM) pre-compiler, translating MLMs into an object
      oriented programming language, C++. Advantages of the C++ approach compared with
      other alternatives are discussed.

PMID- 8156749
TI  - HYDRO: a program for protein hydropathy predictions.
AB  - VAX/VMS programs for predicting protein hydropathy from amino acid sequence with
      several parameters are described. The hydropathy propensities of amino acids were
      normalised to make the different scales and predictions comparable. Another
      program package can be used to study similarity on the secondary structural level
      by comparing, for example, hydropathy predictions. These methods can provide
      valuable information also when there is only low sequence similarity. Amino acid
      residue accessibilities can be shown for known three-dimensional structures in
      addition to predictions. The programs can further be used for searching for a
      suitable prediction method and window size for a group of related proteins when
      the structure of at least one representative is known.

PMID- 8156750
TI  - Microcomputer program for the assessment of one-way, two-way and factorial
      analysis of variance in pharmaceutical data.
AB  - A personal computer program in BASIC for the two-factor factorial analysis of
      variance has been developed. The factorial design is based on and combined with
      previous one-way and two-way ANOVA programs. The performance of the program is
      tested on data obtained from 3 months' consumption of three proprietary
      antibiotic products in four Saudi hospitals.

PMID- 8156751
TI  - Semi-automatic computer construction of three-dimensional shapes for the finite
      element method.
AB  - Precise estimation of spatio-temporal distribution of ions (or other
      constitutives) in three-dimensional geometrical configuration plays a major role
      in biology. Since a direct experimental information regarding the free
      intracellular Ca2+ spatio-temporal distribution is not available to date,
      mathematical models have been developed. Most of the existing models are based on
      the classical numerical method of finite-difference (FD). Using this method one
      is limited when dealing with complicated geometry, general boundary conditions
      and variable or non-linear material properties. These difficulties are easily
      solved when the finite-element-method (FEM) is employed. The first step in the
      implementation of the FEM procedure is the mesh generation which is the single
      most tedious, time consuming task and vulnerable to mistake. In order to overcome
      these limitations we developed a new interface called AUTOMESH. This tool is used
      as a preprocessor program which generates two- and three-dimensional meshes for
      some known and often-used shapes in neurobiology. AUTOMESH creates an appropriate
      mesh by using the mesh generator commercial tool of FIDAP.

PMID- 8156752
TI  - Comparison of different methodologies of heart rate variability analysis.
AB  - Two methodological aspects of heart rate variability (HRV) are tested. Heart rate
      variability and RR interval variability (RRV) are compared in 109 healthy
      subjects using 24-h Holter recordings. Autoregressive power spectrum analysis was
      performed, and the power in three frequency bands was evaluated by two different
      methods: the peak power and the mean power within the band. The power in the low
      frequency (LF) and high frequency (HF) ranges showed greater changes between day
      and night values when RRV was analysed compared with HRV. The mid frequency (MF)
      range power showed no significant change at night with RRV analysis compared with
      a significant decrease with HRV analysis. The different pattern of changes
      between day and night values when using RRV or HRV analysis is explained by the
      non-linear nature of the relationship between RR interval and heart rate and the
      lower heart rate at night. Therefore, depending on the heart rate, there may be
      amplification or attenuation of fluctuations when transforming from one heart
      rate variability method to another. When comparing peak power and mean power
      measurements within the frequency bands, the changes in LF and MF powers were
      similar. However, HF mean power with RRV analysis showed less change at night
      than the peak power and no change with HRV analysis. The explanation lies in the
      fact that respiratory fluctuations at night are much more regular, resulting in a
      sharp high peak in the power spectrum. The peak power is therefore higher at
      night, whereas the total power changes much less or remains unchanged.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156753
TI  - Preoperative assessment and prediction of postoperative results in an artificial
      arterial network using computer simulation.
AB  - A computer model has been developed that can be used to describe the human
      arterial system mathematically. It simulates the complex relationship of
      morphology and hydraulics in the vessel network. After entering patient data into
      a standard vessel model, the mean flow velocity, the flow direction, and the
      blood pressure at each specified point of the flow network can be calculated. The
      vessel picture can be altered and modified with the help of a graphic editor.
      Localized or diffuse stenoses, bypasses with simple or multiple anastomoses, end
      to-end anastomoses, end-to-side anastomoses, etc., can be studied in terms of the
      hydraulic effects on the local situation or on the entire vessel system.
      Experimental results of ultrasonic mean flow data in vessel systems of leg and
      cerebral arteries of patients are compared with calculated values. The predicted
      and measured flow velocities show a mean difference of about 10% indicating that
      such a computer model may be successfully used in the optimal planning of bypass
      operations.

PMID- 8156754
TI  - Quantitative morphology and shape classification of neurons by computerized image
      analysis.
AB  - We describe a new image processing method for semiautomatic quantitative analysis
      of neuronal morphology. It has been developed in a specific image analysis
      environment (IBAS 2.0), but the algorithms and the methods can be employed
      elsewhere. The program is versatile and allows the analysis of histological
      preparations of different quality on the basis of different levels of evaluation
      and image extraction. Some significant algorithms have been implemented (i.e. one
      for multiple focus image acquisition and one for automatic cell body shape
      recognition and classification). A wide set of specific morphological parameters
      has been defined to allow a better mathematical characterization of neuronal
      morphology as regards both dendrite trees and cell bodies. Cell bodies' shapes
      can be classified automatically, defining different neuronal populations. This is
      done by evaluating the number of main dendrites and perikarya shapes through a
      multi-valued-decision-tree based method, tested on somatostatin-positive cells in
      mouse brain. The methods presented have been applied to analysis of neurons, but
      they can well be used for any quantitative morphological study of other cell
      populations.

PMID- 8156755
TI  - Alcohol dermatitis: allergic contact dermatitis and contact urticaria syndrome. A
      review.
AB  - In spite of not knowing the numbers of people exposed and obviously incomplete
      reporting, the known mechanisms of alcohol cutaneous intolerance and the
      literature classified according to mechanisms are listed. Testing techniques for
      delayed- and immediate-types are proposed.

PMID- 8156756
TI  - Concomitant sensitization to triglycidyl isocyanurate, diaminodiphenylmethane and
      2-hydroxyethyl methacrylate from silk-screen printing coatings in the manufacture
      of circuit boards.
AB  - A 48-year-old female silk-screen printer had worked in the manufacture of circuit
      boards for 12 years before she got the first symptoms of dermatitis on her wrists
      and lower arms. On the 1st patch test session, epoxy resin and the remainder of
      the standard series were negative, while a plastics and glues series gave an
      allergic reaction to 4,4'-diaminodiphenylmethane (DDM). The 2nd test session
      revealed allergic reactions to several acrylics, several epoxy compounds and 3
      ink components. According to the material safety data sheets, 1 ink hardener
      contained DDM, but the causative agent in 1 ink and 1 ink hardener remained
      uncertain. The manufacturers of the 2 inks kindly provided us with their
      components for further patch tests. 2 of these components gave allergic
      reactions: triglycidyl isocyanurate (TGIC) and 2-hydroxyethyl methacrylate (2
      HEMA). Our case report shows that the manufacture of circuit boards involves
      exposure to highly sensitizing chemicals. DDM, TGIC and 2-HEMA should be
      remembered as silk-screen printers' potential contact sensitizers in the
      manufacture of circuit boards.

PMID- 8156757
TI  - Diazolidinyl urea: incidence of sensitivity, patterns of cross-reactivity and
      clinical relevance.
AB  - Diazolidinyl urea (DIAZ) is a formaldehyde-releasing preservative used in
      cosmetics and personal-care products, which has been identified as a sensitizing
      agent in contact dermatitis. To determine whether DIAZ sensitization is secondary
      to formaldehyde release or due to its own allergenic properties, we reviewed 708
      consecutive patch tests of patients with various dermatologic complaints.
      Profiles of the 58 individuals (8%) with DIAZ sensitivity were analyzed with
      respect to sex, age, exposures, and chronicity of dermatitis. Significant
      coexistent biocide reactivity was demonstrated for DIAZ and formaldehyde (81%);
      12% reacted to DIAZ alone. We conclude that the primary mode of sensitization of
      DIAZ is via formaldehyde release and that independent contact allergy is less
      frequent.

PMID- 8156758
TI  - Identification of causative chemicals of allergic contact dermatitis using a
      combination of patch testing in patients and chemical analysis. Application to
      cases from industrial rubber products.
AB  - 3 cases of allergic contact dermatitis from industrial rubber products were
      investigated using a combination of patch testing in patients and chemical
      analysis of causative rubber products by gas chromatography (GC), GC-mass
      spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Our
      studies revealed N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), a typical
      rubber allergen, as a causative chemical in a case from a brand of heavy-duty
      rubber gloves and a case from a black rubber ring for car manufacture, and zinc
      ethylphenyldithiocarbamate (ZEPC), a dithiocarbamate (DTC)-type accelerator, as a
      causative chemical in a case from a brand of rubber work gloves: both IPPD and
      ZEPC, which showed positive patch test reactions, were confirmed in the extracts
      of the causative rubber products by GC, GC-MS and/or HPLC.

PMID- 8156759
TI  - Identification of causative chemicals of allergic contact dermatitis using a
      combination of patch testing in patients and chemical analysis. Application to
      cases from rubber footwear.
AB  - 5 cases of allergic contact dermatitis from rubber footwear were investigated by
      a combination of patch testing in patients and chemical analysis of causative
      rubber products. Our studies revealed 2-mercaptobenzothiazole (MBT) and
      benzothiazyl disulfide (MBTS) (typical allergenic accelerators) as causative
      chemicals in 3 cases from children's rubber shoes, ladies' rubber boots and
      ladies' canvas shoes. These 3 patients reacted to mercaptobenzothiazole-type
      accelerators including MBT and MBTS. MBT and MBTS were determined in each item of
      causative footwear by chemical analysis, including extraction by shaking with
      acetone-chloroform (1:1) mixture at room temperature and determination using
      reversed-phase high-performance liquid chromatography (RP-HPLC). Subsequently, we
      identified styrenated phenol (SP), a newly found allergenic antioxidant, as a
      causative chemical in a case from ladies' canvas shoes. The patient reacted to SP
      but not to MBT and MBTS, though SP, MBT and MBTS were determined in the causative
      shoes by gas chromatography (GC), GC-mass spectrometry (GC-MS) and HPLC. We also
      identified p-tert-butylphenol-formaldehyde resin (PTBP-F-R), (a known allergenic
      adhesive ingredient) as a causative chemical in a case from ladies' sneakers. The
      patient reacted to PTBP-F-R but not to p-tert-butylphenol (PTBP), MBT and MBTS.
      These 4 compounds were determined in the causative sneakers by GC, GC-MS and
      HPLC. Thus, our studies revealed that not only known allergens, such as MBT, MBTS
      and PTBP-F-R, but also a newly found one, such as SP, were important causes of
      allergic contact dermatitis from rubber footwear.

PMID- 8156760
TI  - Skin irritant reactivity following experimental cumulative irritant contact
      dermatitis.
AB  - Despite the frequency of irritant contact dermatitis, very little is known about
      the duration of barrier function impairment following cumulative irritant contact
      dermatitis. We studied post-irritation irritant reactivity by assessing the
      response to SLS irritation in previously irritated sites. Cumulative irritant
      contact dermatitis was induced on the forearms of 15 volunteers aged 18 to 50
      years by repeated occluded application of 0.5% SLS 1 h per day over 3 weeks. 3, 6
      and 9 weeks later, previously irritated and unirritated control sites were
      challenged with 2% SLS under occlusion for 23 h. Irritation was assessed by
      visual scoring, transepidermal water loss (TEWL) as an indicator of epidermal
      barrier function, and capacitance as a parameter of epidermal water content.
      While no difference in irritant reactivity between pre-irritated and unirritated
      sites was observed 3 weeks following irritant contact dermatitis, there was a
      significant hyporeactivity of previously irritated skin as expressed by clinical
      scores, TEWL and capacitance at 6 and 9 weeks. Our results indicate that
      epidermal barrier function remains altered even 9 weeks after cumulative irritant
      contact dermatitis. With regard to patch testing, post-irritation hyporeactivity
      might be a cause of false-negative tests on previously irritated sites.

PMID- 8156761
TI  - Contact dermatitis from diazepoxides.

PMID- 8156763
TI  - Allergic contact dermatitis from menthol in peppermint.

PMID- 8156762
TI  - Echographic evaluation of sodium lauryl sulfate (SLS)-induced irritation in mice.

PMID- 8156764
TI  - Systemic contact dermatitis from erythromycin.

PMID- 8156765
TI  - Allergic contact dermatitis from fepradinol in a child.

PMID- 8156766
TI  - Type I hypersensitivity to beer.

PMID- 8156767
TI  - Low irritancy of 2-day occlusive patch test with calcipotriol cream.

PMID- 8156768
TI  - Identification of a printed circuit board causing fibreglass skin irritation
      among electronics workers.

PMID- 8156769
TI  - Primula dermatitis: versatility in its clinical presentation and the advantages
      of patch tests with synthetic primin.

PMID- 8156770
TI  - Patch test reading: a comparison between 2 application methods.

PMID- 8156771
TI  - Contact dermatitis from a moisturizing cream.

PMID- 8156772
TI  - Allergic contact dermatitis from Reflex spray.

PMID- 8156773
TI  - Systemic contact dermatitis from oral prednisone.

PMID- 8156774
TI  - Delayed skin burns from MCI/MI biocide used in water treatment.

PMID- 8156775
TI  - Contact sensitivity among workers in a paint factory.

PMID- 8156776
TI  - Thimerosal-induced bullous contact dermatitis.

PMID- 8156777
TI  - Airborne contact dermatitis from chromate in cement with recall dermatitis on
      patch testing.

PMID- 8156778
TI  - Picric acid.

PMID- 8156779
TI  - Combined allergy to human seminal plasma and latex: case report and review of the
      literature.
AB  - The case is reported of a young atopic woman with combined Type I and possible
      Type IV allergy to human seminal plasma, as well as Type-I allergy to latex.
      Clinical symptoms were swelling and a burning sensation on the vulva and in the
      vulvovaginal area during or after coitus, followed by vesiculation,
      lichenification and the development of generalized eczema. Diagnosis was
      confirmed by investigation (RAST, prick testing, histology). Literature on the
      subject is reviewed.

PMID- 8156780
TI  - Indications for keratoplasty.

PMID- 8156781
TI  - Altered gelatinolytic activities in an apparent unilateral keratoconus patient. A
      case report.
AB  - Recent studies have suggested that one possible cause of keratoconus involves
      increased degradation of the corneal extracellular matrix. Most studies have
      examined corneas from patients with bilateral, sporadic keratoconus. In this
      report, both corneas from a 70-year-old man with a history of familial
      keratoconus and clinical signs of unilateral keratoconus were examined for
      gelatinase activity. Our results demonstrated a qualitative (three additional
      activity bands of 88, 92, and 100 kDa molecular weights) and quantitative
      differences (an apparent increase in overall amounts) in the gelatinolytic enzyme
      profiles of the affected keratoconus cornea as compared with his unaffected
      (nonkeratoconus) cornea, normal corneas, bilateral sporadic keratoconus corneas,
      and cultured keratocytes. In addition, gelatinolytic enzymes were more readily
      extracted from the affected cornea compared with controls. These data lend
      support to the hypothesis of a heterogeneous etiology for keratoconus and to
      previous suggestions that this disorder may be related to an alteration in
      extracellular matrix degradation.

PMID- 8156782
TI  - Increased gelatinolytic activity in keratoconus keratocyte cultures. A
      correlation to an altered matrix metalloproteinase-2/tissue inhibitor of
      metalloproteinase ratio.
AB  - Keratoconus is a noninflammatory corneal disorder characterized by gradual
      stromal thinning and astigmatism. Altered degradation of corneal extracellular
      matrix is a suggested etiology for this disorder. In the present study we
      established keratocyte cultures from normal and keratoconus corneas and
      investigated the roles that matrix metalloproteinases (MMPs) and tissue
      inhibitors of metalloproteinases (TIMP, TIMP-2) may play. After chemical
      modification (reduction and alkylation) to remove the inhibitor and activation of
      enzyme with p-aminophenylmercuric acetate (APMA), keratoconus-conditioned media
      displayed a significant increase (p < 0.05) in the total potential gelatinolytic
      activity when compared with normal culture media treated in a similar manner.
      Basal levels of gelatinolytic activity in keratoconus culture media (no
      reduction, alkylation, or APMA treatment), determined by two different assay
      methods, tended to be about twice that of normal cell cultures. By zymography,
      both keratoconus and normal cultures showed identical enzyme patterns, which
      represented MMP-2 (72 kDa) in its proform and, depending on the treatment of the
      media, varying amounts of activated MMP-2 (65 kDa). This suggests that the
      increased gelatinolytic activity in keratoconus was not correlated with an
      increased appearance of either the 65-kDa-activated form of MMP-2 or a new MMP
      species. In addition, no differences in the amount of MMP-2 were detected that
      could account for the increased activities in keratoconus cultures. However, a
      relative decline in the detectable TIMP levels in keratoconus cultures resulted
      in an apparent three-fold increase in the ratio of MMP-2/TIMP. Northern blots
      showed no significant changes in mRNA levels for MMP-1, MMP-2, MMP-3, TIMP, or
      TIMP-2. These data suggest that a possible alteration in the interaction between
      MMP-2 and TIMP may play a role in the increased gelatinolytic activity seen in
      keratoconus tissues.

PMID- 8156783
TI  - Osteo-odonto-keratoprosthesis. Description of surgical technique with results in
      85 patients.
AB  - Osteo-odonto-keratoprosthesis is a technique designed for patients with severe
      corneal opacification who would be at high risk of graft rejection should donor
      tissue transplantation be performed. Because of the isolation of the prosthetic
      implant from the tissues that the technique provides, the authors are of the
      opinion that it is the only viable option in such patients. The visual outcome
      and complications of the procedure in a series of 85 cases are presented.

PMID- 8156784
TI  - The significance of anterior chamber depth in Fuchs' corneal dystrophy and cornea
      guttata.
AB  - It is sometimes claimed that a relationship exists between Fuchs' dystrophy and
      angle closure glaucoma and that this is an indication for the simultaneous
      performance of keratoplasty and cataract extraction in patients with Fuchs'
      dystrophy. If such a relationship exists, then the anterior chamber depth in
      Fuchs' dystrophy should resemble that in angle closure glaucoma and a significant
      degree of cornea guttata might be expected to be common in angle closure
      glaucoma. In 88 patients with angle closure glaucoma we found that the anterior
      chamber depth was significantly shallower than in cornea guttata or Fuchs'
      dystrophy for acute (p < 0.001), chronic (p < 0.002) or incipient angle closure
      glaucoma (p < 0.001). Cornea guttata and Fuchs' dystrophy were very infrequent in
      these patients with angle closure, only two having cornea guttata and one Fuchs'
      dystrophy. These results do not support a relationship between angle closure
      glaucoma and Fuchs' dystrophy or cornea guttata and do not justify performing
      combined cataract surgery and keratoplasty in all cases of cornea guttata or
      Fuchs' dystrophy undergoing keratoplasty. Each case should be assessed on its
      merits and combined surgery should be reserved for patients shown to have a
      shallow anterior chamber or significant cataract.

PMID- 8156785
TI  - Influence of topically applied cyclosporine A in olive oil on corneal epithelium
      permeability.
AB  - The effect that topically administered cyclosporine A (CsA) dissolved in olive
      oil has on corneal epithelial permeability was determined by fluorophotometry.
      Twenty-six healthy volunteers, who had no ocular or general disease and were not
      receiving any topical or systemic treatments, were studied. A Fluorotron Master
      fluorophotometer was used. Measurements were taken before and 45 min after the
      instillation of 40 microliters of a 2% aqueous solution of sodium fluorescein
      without preservatives. Basal corneal epithelial permeability, as well as the
      permeability 24 h after the instillation of 2% CsA-olive oil and of the solvent
      alone, were calculated. Under sterile conditions, the Sandimmun oral solution
      (Sandoz, Basel, Switzerland) was used to prepare the topical 2% CsA. Immediately
      after the 2% CsA-olive oil or the solvent alone were instilled, the volunteers
      complained of itching for approximately 1 h and developed punctate keratopathy,
      which improved the next day. Epithelial permeability 24 h after instillation of
      2% CsA-olive oil increased 7.03 times (p < 0.001), and that of the solvent alone
      increased 6.68 times (p < 0.001). No differences in corneal permeability were
      found between CsA-olive oil and the vehicle (p = 0.651). We concluded that the
      olive oil used to dissolve CsA is responsible for the increased corneal
      epithelial permeability.

PMID- 8156786
TI  - In vitro alteration of Schirmer's tear strip wetting by commonly instilled
      anesthetic agents.
AB  - The Schirmer's tear test is often performed with topical anesthesia to reduce
      reflex tearing. Fluress (Barnes-Hind, Sunnyvale, CA, U.S.A.) and Fluoracaine
      (Akorn, Abita Springs, LA, U.S.A.) are commonly used anesthetic-fluorescein
      preparations that contain viscous additives. Because the rate of Schirmer's strip
      wetting is dependent on capillary action, a property related to solution
      viscosity and surface tension, spurious results may be obtained if these agents
      are used for anesthesia. We report in vitro Schirmer's strip wetting rates for
      various concentrations of Fluress and Fluoracaine, as well as pure fluorescein
      solution using a tear substitute (Dacriose; IOLAB, Claremont, CA, U.S.A.) as a
      diluent. Results showed a direct concentration-dependent reduction of Schirmer's
      strip wetting with time for both Fluress and Fluoracaine dilutions compared with
      Dacriose alone (p < 0.001) or Dacriose-fluorescein solutions (p < 0.001). In
      addition, Schirmer's wetting with Dacriose-fluorescein solutions caused a
      separation of the Dacriose and fluorescein wetting fronts (p < 0.001) but did not
      affect the overall Dacriose wetting. These data have clinical implications
      concerning false-positive results when testing for dry eyes.

PMID- 8156787
TI  - A rapid fluorometric assay for tear fluid plasmin activity.
AB  - A rapid (5- to 10-min), sensitive (detection limit 0.6 IU/L), and moderately
      specific fluorometric plasmin assay for small volume tear fluid samples was
      developed. Addition of albumin (up to 0.1% final concentration) to the assay
      buffer improved the sensitivity of the test so that plasmin activity in healthy
      controls could be detected. pH in the reaction buffer was 8.0, Michaelis-Menten
      constant for the substrate, H-D-Val-Leu-Lys.7-amido-4-methyl-coumarin (AMC), was
      0.28 mM, and final substrate concentration in the reaction buffer was 1 mM. Intra
      and interassay imprecisions were 1.6 and 4.4%, respectively at a plasmin level
      of 10 IU/L. Tear fluid flow was significantly higher in the patients than in the
      healthy controls, and this dilatory effect must be considered when using plasmin
      determination for diagnostic purposes. This effect was counteracted by correcting
      the plasmin activity values by tear fluid flow. Plasmin flux is plasmin activity
      (microIU) secreted in units of time (min). This parameter showed highly
      significant differences between the patients and controls. All patients with
      microbial keratitis, corrosive trauma, ocular trauma, herpetic infection, and
      other diseases showed highly significant elevation of plasmin flux compared with
      controls. The highest plasmin flux values (several hundredfold that of controls)
      were recorded in patients with severe corneal ulcers. Few patient samples showed
      some involvement of other proteases, which were not inhibited by aprotinin.

PMID- 8156788
TI  - Increased interleukin-1 activity in the injured vitamin A-deficient cornea.
AB  - Injury to a vitamin A-deficient cornea leads to severe acute inflammation often
      culminating in ulceration. We report on possible regulatory mechanisms involved
      in the pathogenesis of corneal inflammation in vitamin A deficiency. Thymocyte
      comitogenic assay and interleukin (IL)-6 induction in corneal fibroblasts have
      shown that thermally injured and mechanically abraded vitamin A-deficient rat
      corneas produce much higher levels of an IL-1-like factor as compared with
      uninjured or injured, normal control corneas. This was confirmed by antibody
      capture enzyme immunoassay, which detected high levels of IL-1 alpha and IL-1
      beta in injured vitamin A-deficient corneas. To our knowledge this is the first
      report describing the induction of IL-1 in the vitamin A-deficient cornea by
      thermal and mechanical injuries. When mechanically injured corneas were screened
      for chemotactic activity, they were found to contain significantly higher levels
      of a chemoattractant as compared with similarly injured, normal control corneas.
      Chemotactic activity [expressed as a percentage of a known chemotactic
      tripeptide, formyl-methionyl-leucyl-phenylalanine (fMLP), found in medium
      harvested from vitamin A-deficient corneas] averaged 58.8 +/- 8.9% (SEM) as
      compared with 12.6 +/- 5.4% in medium conditioned by normal corneas. Checkerboard
      analysis confirmed that the activity in vitamin A-deficient cornea conditioned
      medium was chemotactic and not chemokinetic. These results demonstrate a
      correlation between IL-1 levels and severity of inflammation in the injured
      vitamin A-deficient rat cornea.

PMID- 8156789
TI  - Aggravation of herpetic stromal keratitis after murine epidermal grown factor
      topical application.
AB  - We evaluated the epithelializing-promoting effect of a concentration of 0.005
      mg/ml murine epidermal growth factor (mEGF), topically administered four times
      daily, on the herpes simplex virus 1 (HSV-1) corneal ulcers of the rabbit eye.
      The severity of the herpetic lesions was evaluated clinically, after the time
      course of the severity of epithelial keratitis, conjunctivitis, iritis, and
      stromal disease, for 14 days. A histological assessment was performed in the
      middle and at the end of the follow-up. The stromal keratitis of the mEGF-treated
      group was significantly more severe than the keratitis exhibited by the placebo
      treated rabbits (Y = X3 X2*X4; p = 0.0001). There were no significant differences
      in the degree of conjunctivitis, epithelial keratitis, iritis, and virus shedding
      between these groups. No evidence of a toxic effect of mEGF or placebo was found
      in the mock infected rabbit eyes. More studies, using different herpes virus
      strains and a broad range of murine and human EGF concentrations, are mandatory
      to ascertain the general significance of these results. Meanwhile, caution is
      recommended when using mEGF in the presence of an occult or manifest herpetic eye
      disease.

PMID- 8156790
TI  - Transplantation of corneal endothelial cells using a cell carrier device.
AB  - Penetrating keratoplasty is currently the only treatment for corneal endothelial
      dysfunction. Although corneal transplantation has a high success rate, a few
      problems still remain, such as the limited availability of donor grafts, the
      change in refraction after penetrating keratoplasty, and the higher chance of
      immune rejection. In this study, a coated hydrogel lens (Chiron Ophthalmics Inc.,
      Irvine CA, U.S.A.) has been used as a carrier to transplant cultured homologous
      kitten and rabbit corneal endothelial cells into adult cats and rabbits. The
      transplantation procedure was the same in both species. Corneal endothelial cells
      from homologous rabbits or cats were seeded on coated hydrogel lenses and
      cultured until they reached a complete monolayer with an average cell density of
      2,500 cells/mm2. Five weeks before transplantation surgery, corneal endothelial
      cells were scraped to induce corneal edema. The cell carrier device was then
      transplanted as follows: a trephine cut (7.7 mm) was made into the stroma,
      producing an outer corneal plug. The inner cornea was then cut by using a 5.5-mm
      trephine, and this inner plug was discarded. The implant was inserted and the
      outer corneal plug was sutured back into place. Corneas cleared completely within
      3 days in both rabbits and cats, and stayed clear for an average of 40 days in
      rabbits and 50 days in cats. The histopathological evaluation of the rejected
      grafts showed vascularized retrocorneal membrane formation in cats, whereas in
      rabbits severe cellular infiltration of the stroma with neovascularization
      occurred without retrocorneal membrane formation.

PMID- 8156791
TI  - In vivo scanning slit confocal microscopy of Acanthamoeba keratitis. A case
      report.
AB  - A 29-year-old woman presented with clinical signs and symptoms of Acanthamoeba
      keratitis. Scanning slit confocal microscopy revealed a 26-mu-diameter object,
      resembling an Acanthamoeba cyst, in the anterior stroma. Numerous ovoid objects
      (possibly inflammatory cells, trophozoites, or altered keratocytes) were present.
      Normal keratocyte nuclei and the anterior corneal mosaic, readily imaged by
      scanning slit confocal microscopy of the normal cornea, were noticeably absent.
      Subsequent corneal biopsy confirmed the diagnosis of Acanthamoeba keratitis.

PMID- 8156792
TI  - Acanthamoeba keratitis. Resolution after epithelial debridement.
AB  - Two patients presented with dendritiform epithelial irregularities of the cornea
      that were unresponsive to topical acyclovir. Both were soft contact lens wearers
      who had practiced inadequate lens hygiene. Acanthamoeba was cultured from a
      shallow corneal biopsy of one patient and from the contact lens of the other.
      Epithelial debridement resolved the condition in both patients without
      concomitant treatment with antiamoebic agents.

PMID- 8156793
TI  - Primary gelatinous drop-like corneal dystrophy in a white woman. A pathologic,
      ultrastructural, and immunohistochemical study.
AB  - A white female with primary gelatinous drop-like corneal dystrophy (PGDD) was
      followed from the ages of 8 to 37 years. During this time, she underwent repeated
      lamellar and penetrating keratoplasties on both sides due to relapsing bilateral
      corneal opacifications. The diagnosis of PGDD was based on the histology of the
      corneal specimens obtained at 10 and 36 years of age, as well as on the
      characteristic clinical appearance and course. Electron microscopy showed typical
      amyloid fibrils. Immunohistochemical staining was mildly positive for amyloid AL
      (light chain), but negative for amyloid AA, AF, AB, and keratin. Thus, the
      precursor protein of the amyloid deposits in PGDD might derive from
      immunoglobulins, e.g., from the tear film. However, the precursor protein might
      derive from a different origin altogether. In that case, the positive staining
      for amyloid AL would translate nonspecific absorption of fragments of light
      chains.

PMID- 8156794
TI  - Human corneal endothelial tolerance to glycerol, dimethylsulfoxide, 1,2
      propanediol, and 2,3-butanediol.
AB  - We exposed human corneas to various concentrations of four cryoprotectants by one
      of two methods: a gradual increase to the final concentration (ramp method) and a
      series of steps to the final concentration (step method). Endothelial damage was
      manifest as a decrease in the number of endothelial cells per unit area. The
      highest concentrations that did not cause a loss of endothelial cells by the ramp
      and step methods, respectively, were 4.3 and 2.0 M glycerol, 2.0 and 4.3 M
      dimethylsulfoxide, 2.0 and 3.0 M 1,2-propanediol, and 2.0 and 2.5 M 2,3
      butanediol. The ramp method achieved higher final concentrations with the more
      slowly permeating glycerol, but required low toxicity. The step method achieved
      higher final concentrations with the more toxic cryoprotectants by limiting the
      exposure time, but required more rapid permeation. None of the four
      cryoprotectants was tolerated at concentrations sufficient for vitrification at
      practical cooling and warming rates.

PMID- 8156795
TI  - Cryopreservation of the mammalian kidney. I. Transplantation of rabbit kidneys
      perfused with EC and RPS-2 at 2-4 degrees C.
AB  - The requirements of organ cryopreservation differ from those of conventional
      organ preservation. The encouraging results of Karow's group with dog kidneys
      transplanted after perfusion with more than 4 M dimethyl sulfoxide were based on
      an RPS-2 (renal preservation solution 2) vehicle solution, but transplantation of
      rabbit kidneys after perfusion with RPS-2 has not been reported. We evaluated RPS
      2 in comparison to Euro-Collins solution (EC) using a modified technique for
      rabbit kidney autotransplantation and a computer-based organ perfusion machine
      designed for the introduction and removal of cryoprotective agents. Consistent
      success in rabbit kidney transplantation was found to depend on the anesthetic
      used, the hydration volumes administered, and direct ureter-to-ureter
      anastomosis. RPS-2 was found to be equivalent to EC for short-term (about 5 h)
      preservation by either perfusion or simple cold storage. However, good results
      with EC were associated with perfusion at 4 degrees C, recovery being
      significantly worse at 2 degrees C. In addition, we found that the solitary
      rabbit kidney is not able to fully compensate for the loss of the contralateral
      kidney, the result being persistent (to 3 weeks) mild elevation of serum
      creatinine, potassium, and calcium and persistent moderate reduction of serum
      phosphate. These results establish perfusates, perfusion conditions,
      transplantation techniques, computer-based perfusion control techniques, and a
      general clinical baseline that are permissive of further direct experiments on
      cryoprotectant introduction and removal.

PMID- 8156796
TI  - Effects of hypothermia upon endothelial cells: mechanisms and clinical
      importance.
AB  - The endothelial cell is vital in the regulation of blood vessel wall structure,
      vasomotor tone, and thrombogenicity. Hypothermic temperatures alter both the
      physiological and biochemical dynamics of endothelial cells. However, there has
      been no systematic investigation of the influence of cold temperatures upon
      endothelial cell biology. This review summarizes the current clinical areas of
      interests, identifies the problems, and addresses the fundamental requirement for
      further research in endothelial cell cryobiology.

PMID- 8156797
TI  - Evaluation of cold reperfusion as an indicator of viability in stored organs: a
      31P NMR study in rat liver.
AB  - Rat livers were studied during hypothermic resuscitation perfusion using 31P
      nuclear magnetic resonance (NMR) spectroscopy as a viability index. Livers were
      stored for 48 h after being flushed either with a synthetic solution containing
      plasma-equivalent concentrations of cations, plus citrate and including gelatin
      polypeptides as colloid (GC solution), or with a modified lactobionate/raffinose
      [University of Wisconsin (UWC)] solution. After 48 h in either solution, all NMR
      detectable ATP plus ADP had disappeared, inorganic phosphate had increased
      markedly and pH in the livers had become acidotic. During cold reperfusion, ATP
      was resynthesized, inorganic phosphate declined, and pH returned toward normal
      values. ATP recovery and decrease in tissue inorganic phosphate were
      significantly greater (P < 0.02 and P < 0.005, respectively) after 1 h cold
      reperfusion with the modified UW compared with reperfusion with the GC. 31P NMR
      spectroscopy was able to detect differences in the metabolic responses of livers
      stored in different solutions, and coupled with cold reperfusion may be a useful
      indicator of viability.

PMID- 8156798
TI  - Localization of freezing injury in articular cartilage.
AB  - In order to improve techniques for cryopreservation of articular cartilage, a
      study has been carried out to assess localization of cryoinjury in intact
      articular cartilage. Osteochondral dowels taken from the femoral condyles of
      sheep were subjected to graded freezing in the presence and absence of a
      cryoprotectant (10% DMSO). The graded freezing technique involves slow cooling (1
      degree C/min) to various subzero temperatures before either rapid warming or
      rapid cooling by plunging in liquid nitrogen. This protocol allows assessment of
      the separate effects of rapid and slow freezing which damage cells in different
      ways, and the effects of cryoprotectants on the different types of damage. To
      assay damage, thin slices of cartilage were cut with a vibratome, which allows
      viable cells within the matrix to be observed microscopically. Injury was
      assessed by staining with fluorescent dyes to indicate damage to the plasma
      membrane. In general, tissue response was similar to that of cell suspensions,
      showing at least two mechanisms of injury acting on the cells: one at slow
      cooling rates and another at rapid cooling rates. The primary effect of DMSO was
      to reduce injury due to slow cooling. When the location of injury within the
      tissue was examined, it was found that chondrocytes of the intermediate layer
      were injured more extensively than those of either the deep or superficial
      layers.

PMID- 8156799
TI  - Osmotic effects on ram and human sperm membranes in relation to thawing injury.
AB  - The effects of hyposmotic and hyperosmotic stresses on ram and human spermatozoa
      were examined. Human spermatozoa exhibited a precipitate decline in survival at
      osmolalities below 90 mOsm caused by cells swelling beyond their maximum volume
      to-surface area ratio and lysing. Ram spermatozoa exhibited a progressive decline
      in cell survival at relatively small hyposmotic stresses before exceeding their
      maximum volume-to-surface area ratio; this prelytic cell loss could be prevented
      by decreasing the osmolality in a series of 25-mOsm steps. Repeated hyposmotic
      stress experiments indicated that cells sensitive to prelytic damage constitute a
      discrete subpopulation within the ram ejaculate. Spermatozoa of both species were
      apparently resistant to hyperosmotic stresses; human spermatozoa maintained
      membrane integrity when subject to stresses up to 2.5 Osm and ram spermatozoa up
      to 1 Osm. However, ram spermatozoa suffered an almost complete and irreversible
      loss of motility above 600 mOsm. Spermatozoa of both species exposed to
      hyperosmotic stress and returned to isosmotic conditions exhibited significant
      cell damage, although ram spermatozoa were the more vulnerable. These
      observations are related to cryopreservation of spermatozoa.

PMID- 8156800
TI  - Applications for cryopreserved blood vessels in pharmacological research.
AB  - The development of drugs in cardiovascular research involves in vitro studies
      that are generally performed on freshly isolated blood vessels. Naturally, data
      obtained from human tissues would be the most accurate and predictable for human
      pharmacology. However, the main problems are that the supply of fresh human
      material is unpredictable and the tissue has a very short life span. Storage in
      physiologic salt solution at 4 degrees C, the most common practice to preserve
      isolated blood vessels, induces rapid and progressive changes of physiologic and
      functional properties within a few days. Cryopreservation of isolated blood
      vessels at -70 to -196 degrees C in a medium containing Me2SO offers the prospect
      of virtually infinite storage of the material with the only damage being that
      associated with the freezing and thawing process. Despite certain changes, such
      as reductions in contractile forces and endothelial functions, the main
      biochemical properties, uptake mechanisms, and affinities of most agonists and
      antagonists have been shown to be well preserved after cryopreservation. Hence,
      this technique offers clear potential for ensuring the supply of vascular
      material for pharmacological studies.

PMID- 8156801
TI  - Structural and functional consequences of bypass grafting with autologous vein.
AB  - An understanding of the consequences of autologous vein grafting reveals both the
      reasons why cryopreserved allogenic veins are being used clinically and how they
      are most likely to be expected to fail. Autologous vein bypass grafts are
      characterized by a series of distinct biological properties that influences their
      in vivo patency. Current surgical practice ensures that the endothelium of vein
      grafts is preserved at the time of implantation and that there is minimal damage
      to the smooth muscle cells. After implantation, the endothelial cells show
      varying degrees of morphological changes that are maximal within the first 3 days
      after grafting. In autografts, extensive endothelial denudation does not appear
      to occur. During the initial grafting period, the smooth muscle cells change from
      a contractile phenotype to a synthetic phenotype, migrate from the media,
      proliferate in the intima, and lay down connective tissue. Thereafter,
      endothelial cell changes regress and the smooth muscle cells return to their
      contractile phenotype. Perioperative manipulation of vein grafts results in
      decreased endothelial cell function but preservation of smooth muscle cell
      responsiveness. Postoperatively endothelial cell-mediated relaxation to
      acetylcholine is lost and smooth muscle cell contractility is decreased. Within 7
      days after implantation, smooth muscle cell contractility returns and, with time,
      becomes markedly greater than that of the control vein. Endothelium-mediated
      relaxation to acetylcholine never returns in vein grafts and this loss of
      endothelial cell function appears to be related to receptor-coupled G-protein
      defects. Smooth muscle cell contractility remains abnormal. Many of the intimal
      hyperplastic lesions in vein grafts progress to stenosis or become sites of
      accelerated atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156802
TI  - Effects of cryopreservation upon vein function in vivo.
AB  - This review covers experimental and clinical experiences with transplantation of
      allogeneic veins processed by slow rate cooling with 2.5% (W/V) chondroitin
      sulfate and 1 M dimethylsulfoxide. These results are contrasted with the results
      obtained using dimethylsulfoxide alone. The short-term patency of experimental
      autologous (100%) and allogeneic (70-100%) cryopreserved veins may be attributed
      to the combination of "no-touch" procurement techniques employing the smooth
      muscle relaxant papaverine, the chondroitin sulfate preservation method, and
      recipient therapy. Explanted autografts retain many cell and tissue functions. In
      contrast, explanted allografts demonstrate short-term loss of endothelial cells
      and smooth muscle function, both of which subsequently return. Clinically there
      have been positive short-term correlations between good initial runoff from the
      graft site and 1-year patency (68-74%) and limb salvage (94%) rates. In contrast,
      grafts with poor initial runoff, composite grafts, or grafts requiring secondary
      reconstruction resulted in lower 1-year patency (40-44%) and limb salvage (64%)
      rates. More experience, larger study groups, and longer follow-up are necessary
      to evaluate the clinical performance of chondroitin sulfate-preserved grafts. In
      the meantime, chondroitin sulfate-preserved veins are reserved for coronary
      artery bypass or peripheral bypass patients in the absence of suitable autologous
      vessels.

PMID- 8156803
TI  - Cryopreservation of coronary endothelium and endothelial-mediated responses.
AB  - Limited availability of functionally viable biological tissues for graft
      transplantation and scientific research necessitates the development of an
      effective storage method for preserving existing tissue samples. In this report
      we briefly reviewed recent attempts in the cryopreservation of coronary
      endothelium and endothelial-mediated vasoregulatory function. In contrast to
      partial preservation of vascular smooth muscle cell function, cryostorage of
      coronary arteries in dimethyl sulfoxide and fetal calf serum resulted in a near
      complete preservation of the endothelium and its vasoregulatory function. This
      protection was observed in both animal and human epicardial conduit coronary
      arteries, as well as in dog intramyocardial resistance arteries. The apparent
      better preservation of the latter resistance arteries, with a luminal diameter
      less than 50 microns, is consistent with earlier findings that cryopreservation
      efficacy improves with fewer and less packing of cells. To further investigate
      the cryopreservation of endothelial function, we cryostored canine cardiac valves
      and evaluated the vasorelaxant effects of valvular endothelium-derived vasoactive
      factors using a bioassay system. As was observed with intact coronary arteries, a
      near complete preservation of valvular endothelium and its production of
      vasoactive factors was noted following the freeze and thaw procedures. Thus,
      these results demonstrate that cryopreservation may provide a useful and
      efficient storage method for the conservation of limited supplies of biological
      vascular tissues for graft transplantation and scientific research.

PMID- 8156804
TI  - Cryopreserved microvascular conduits: current applications and future prospects.
AB  - Modern cryopreservation techniques have resulted in the clinical use of
      cryopreserved allograft heart valves and large diameter veins. In addition to
      these large vascular tissues, there is a need for small-diameter vascular
      allografts. We review our studies of cryopreserved rat microvenous allografts (1
      mm diameter) in both the arterial and venous systems. The clinical utilization of
      cryopreserved allografts in reconstructive microsurgery and the potential
      problems associated with the use of allogeneic tissues will be addressed. Further
      applications for vascular cryopreservation in reconstructive surgery include
      small-diameter arteries, vascularized tissue flaps, and limbs.

PMID- 8156806
TI  - Suicide attempts and self-injury in prisons.

PMID- 8156805
TI  - Effect of cold on ischemia--reperfusion-induced microvascular permeability
      increase in cat skeletal muscle.
AB  - The effects of reduced temperature during ischemia (I) upon microvascular
      permeability and resistance increases during reperfusion (R) were assessed in
      skeletal muscle. Protein solvent-drag reflection coefficients (sigma f) and
      changes in vascular resistance were measured during 37 degrees C reperfusion of
      isolated, whole-blood perfused cat hindlimbs after the limbs had been subjected
      to 3.5 h of ischemia at several temperatures. sigma f was determined from the
      disappearance rates of water and protein from the circulating perfusate during a
      period of induced microvascular fluid filtration. The I/R procedure at 37 degrees
      C caused sigma f to fall from approximately 0.85 to approximately 0.5, indicating
      a large increase in microvascular permeability. Hypothermic ischemia at 30, 22,
      17, or 12 degrees C totally abolished this drop in sigma f. However, when the
      ischemia was at approximately 5 degrees C, there was a significant fall in sigma
      f to approximately 0.7, which was similar to the value we found previously with 5
      h of continuous perfusion at this low temperature. The normothermic I/R procedure
      led to an increase in vascular resistance of approximately 250% above the value
      measured prior to I/R. Hypothermic ischemia totally abolished this resistance
      increase, except for the lowest temperature, for which the increase was 150%.
      Therefore, hypothermia can prevent the microvascular dysfunction caused by 3.5 h
      of ischemia at 37 degrees C in this preparation. However, when the temperature
      was reduced too far (approximately 5 degrees C), a cold injury to the
      microvascular resulted in permeability and resistance increases.

PMID- 8156807
TI  - The unique role of the volunteer in suicide prevention.

PMID- 8156808
TI  - Letters across the Atlantic.

PMID- 8156809
TI  - Suicide in the elderly: cross-cultural issues in late-life suicide.

PMID- 8156810
TI  - Suicidal or manipulative?--Does it really matter?

PMID- 8156811
TI  - Ukrainian adolescents.

PMID- 8156812
TI  - The implications of Tom's case: guidelines and protocols.

PMID- 8156813
TI  - A support group for people bereaved through suicide.
AB  - Although much research has been performed in recent years on the prevention of
      suicide, less attention has been focused on helping the persons left behind. This
      article outlines the history of establishing a support group for people who have
      been bereaved through suicide in an Australian city. It describes the
      difficulties in establishing the group, its structure, management, and helping
      functions, and the experiences gained from the initial 7 years of operation. The
      article has been written in response to requests from medical, social, and lay
      agencies for information in establishing similar support groups.

PMID- 8156814
TI  - Suicide following attempted suicide: a study of an unsuccessful intervention.
AB  - Unsuccessful interventions are often the best way to improve methods and
      techniques. This article presents a case study of a 55-year-old housewife who
      committed suicide after psychiatric inpatient treatment following a previous
      severe suicide attempt. The social and psychological situation of the patient is
      described, with special emphasis on her relationships with her husband, the
      therapist, and the other staff members on the ward. The steps in her "suicidal
      career" are described. The article then discusses the significance of this case,
      and the conclusions that were drawn by the therapy team about how inpatient
      treatment after suicide attempts could be better managed.

PMID- 8156815
TI  - Hopelessness and the tendency to commit suicide in the course of depressive
      disorders.
AB  - In patients with major affective disorders, research has indicated that the
      extent of hopelessness is a promising variable for predicting suicide. In this
      prospective follow-up study, the predictive power of Beck's hopelessness scale
      (HS) was investigated in 61 depressive inpatients. The examination included the
      HS, the Beck Depression Inventory (BDI), and personal interviews at admission, at
      discharge, and 1 year after discharge. There were eight suicide attempts and two
      suicides during the follow-up period. The sensitivity of the HS was high, i.e., a
      score of 8 or more correctly identified 90% of the eventual suicidal actions, but
      the percentage of false-positives was also high. The HS score at discharge
      differentiated between the groups with and without suicidal behavior during
      follow-up, as did the BDI. Several limitations of these findings are discussed.

PMID- 8156816
TI  - Gender differences among adolescent suicide attempters.
AB  - When males attempt suicide, they often use more lethal and violent methods than
      females. However, this article suggests that gender alone is not especially
      useful in assessing the seriousness of adolescent suicide attempts. In the study
      discussed here, the sociodemographic and psychological characteristics of female
      and male suicide attempters seen in a pediatric hospital are compared. There were
      no sociodemographic differences between the groups. Boys and girls were similar
      when assessed regarding suicidal ideation, depression, and hopelessness. More
      males than females were diagnosed with conduct disorders. Some items on the
      Suicide Intent Scale indicated that boys exhibited more serious intentionality
      than girls. Division of the sample based on suicide intentionality resulted in
      differences in the level of reported depression.

PMID- 8156817
TI  - Suicide in Estonia and other former USSR republics.

PMID- 8156818
TI  - Challenges in preventing suicide.

PMID- 8156819
TI  - Suicide in Slovenia.

PMID- 8156820
TI  - Effect of leukopenia on experimental post-traumatic retinal detachment.
AB  - Macrophages are invariably present in the intraocular membranes of patients with
      traumatic proliferative vitreoretinopathy (PVR). There are two sources from which
      these macrophages could be recruited: adjacent tissues and the systemic
      circulation. In the study described herein, the role of circulating white blood
      cells and monocytes in experimental, traumatic PVR was studied. The circulating
      white blood cells of 20 rabbits were depleted by intravenous injection of
      strontium-89. Posterior perforating eye injury with subsequent intravitreal
      injection of autologous whole blood or autologous activated macrophages was then
      performed on these leukopenic animals. The experiments demonstrated that severe
      bone marrow depression reduced significantly the incidence of retinal detachments
      in eyes receiving whole blood, and reduced the severity of retinal detachments in
      eyes injected with activated macrophages. An association between the degree of
      leukopenia, monocytopenia, and protection from retinal detachment was
      demonstrated. These results support the hypothesis that macrophage infiltration
      is an important component of intraocular cellular proliferation, but does not
      exclude the role of other types of white blood cells in the pathogenesis of PVR.

PMID- 8156821
TI  - Increased gelatinolytic and caseinolytic activity in the thermally injured,
      nutritionally compromised rat cornea: detection of a 27-kDa lymphoreticular cell
      associated caseinase.
AB  - This study assesses the impact of various forms of injury on matrix degrading
      enzymes in nutritionally compromised rat corneas. In vitamin A-deficient
      (nutritionally compromised) and normal control corneas, in vivo or ex vivo mild
      mechanical abrasion did not appreciably alter the activity of either the 65-kDa
      or the 92-kDa gelatinases. In contrast, after thermal injury, while no
      appreciable change was detected in activity associated with the 65-kDa gelatinase
      in either vitamin A-deficient or normal control corneas, 92-kDa gelatinolytic
      activity was consistently higher in corneas from both groups, although activity
      associated with nutritionally compromised corneas was much higher. In these
      corneas, thermal injury also induced the expression of two high molecular weight
      (approximately 130-kDa and 225-kDa) gelatinases and a 27-kDa caseinase. While
      gelatinases were totally inactivated by inhibitors of metalloproteinases such as
      1,10-phenanthroline and Galardin MPI, the 27-kDa caseinase showed considerable
      susceptibility to a mixture of serine protease inhibitors (aprotinin, dichloro
      isocoumarin and pA-PMSF [(4-amidino-phenyl)-methane-sulphonyl fluoride].
      Furthermore, unactivated-lymphoreticular cells from either nutritionally
      compromised or normal control animals contained a 24- and 27-kDa caseinase,
      however most of the activity was due to the 24-kDa caseinase. In contrast,
      glycogen-activated lymphoreticular cells contained a preponderance of the 27-kDa
      caseinase. Activated-lymphoreticular cells also expressed 92-kDa, 130-kDa and 225
      kDa gelatinases. The presence of low molecular weight caseinases in
      lymphoreticular cells implicates them as the source of these enzymes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156822
TI  - Docosahexaenoic acid is taken up by the inner segment of frog photoreceptors
      leading to an active synthesis of docosahexaenoyl-inositol lipids: similarities
      in metabolism in vivo and in vitro.
AB  - Retinal uptake and metabolism of docosahexaenoic acid (DHA) was studied in vivo
      in frogs 1, 2, and 6 hours after dorsal lymph sac injections of [3H]-DHA (50
      microCi/g). Light microscope autoradiography and biochemical techniques were used
      to compare the profiles of cellular uptake and lipid labeling with those obtained
      from 6 hour [3H]-DHA retinal incubations (final DHA concentration, 0.11 and 25
      microM). Light microscope autoradiography demonstrated that rod photoreceptor
      ellipsoids and synaptic terminals preferentially labeled both in vivo and in
      vitro conditions. Also, the cytoplasm and oil droplets of retinal pigment
      epithelial cells became very heavily labeled after 6 hours of in vivo labeling.
      Phosphatidic acid showed the highest labeling in one hour, while other
      phospholipids accumulated label throughout the 6 hours. At that time point, most
      label was recovered in phosphatidyl-ethanolamine (37%), phosphatidylcholine
      (27%), and phosphatidylinositol (16%), the latter displaying 1.6-fold higher
      labeling than phosphatidylserine. The profile of labeled lipids was similar to
      that obtained in vitro when the concentration of DHA was in the nanomolar range.
      Our results suggest that de novo lipid synthesis is a major route for
      esterification of [3H]-DHA into retinal lipids, giving rise to an early and rapid
      labeling of DHA-phosphatidylinositol, both in vivo and in vitro, when DHA is
      present at low concentrations. Furthermore, the profile of labeled retinal cells
      under in vivo conditions closely resembles in vitro DHA labeling.

PMID- 8156823
TI  - Significance of Bruch's membrane in the creation of iatrogenic chorioretinal
      venous anastomosis.
AB  - Iatrogenic retinal to choroidal vein anastomoses, as a method of bypassing
      retinal venous occlusions has been reported in dogs in which Bruch's membrane is
      poorly formed. In order to determine whether chorioretinal venous anastomoses can
      be induced in an animal with a Bruch's membrane that is well developed as in
      humans, pigmented rats were chosen. A high intensity, small spot size argon green
      laser beam of 514 nm was used to induce the anastomosis. Three out of 5 rat eyes
      developed a retinal vein to choroidal vein anastomosis. The success rate of
      iatrogenic retinal to choroidal vein anastomoses in the rat was comparable to
      that obtained in the dog. This study suggests that Bruch's membrane was not
      significant in the creation of an iatrogenic chorioretinal venous anastomosis.

PMID- 8156824
TI  - Molecular chaperone properties of the high molecular weight aggregate from aged
      lens.
AB  - The high molecular weight aggregate (HMWA) fraction was isolated from the water
      soluble proteins of aged bovine lenses. Its composition and ability to inhibit
      heat-induced denaturation and aggregation were compared with the lower molecular
      weight, oligomeric fraction of alpha isolated from the same lens. Although the
      major components of both fractions were the alpha-A and alpha-B chains, the HMWA
      fraction possessed a decreased ability to protect other proteins against heat
      induced denaturation and aggregation. Immunoelectron microscopy of both fractions
      demonstrated that alpha particles from the HMWA fraction contained increased
      amounts of beta and gamma crystallins, bound to a central region of the
      supramolecular complex. Together, these results demonstrate that alpha
      crystallins found in the HMWA fraction possess a decreased ability to protect
      against heat-induced denaturation and aggregation, and suggest that at least part
      of this decrease could be due to the increased presence of beta and gamma
      crystallins complexed to the putative chaperone receptor site of the alpha
      particles.

PMID- 8156825
TI  - Differences in the acyl composition of the platelet-activating factor (PAF)
      precursor and other choline phosphoglycerides of the rabbit retinal rod outer
      segments and neural retina.
AB  - Choline phosphoglycerides comprise almost half of vertebrate retinal
      phospholipids. This lipid pool contains the precursor of the potent lipid
      mediator, platelet-activating factor. The acyl composition and distribution of
      the different subclasses of the choline phosphoglycerides (alkylacyl-[or the
      precursor of platelet-activating factor], alkenylacyl-[or choline plasmalogen]
      and diacyl-glycero-3-phosphocholine) were studied in intact rabbit retina, neural
      retina and rod outer segments. Choline phosphoglycerides were isolated by high
      performance liquid chromatography and derivatized by acetylation after
      phospholipase C treatment. The derivatives were purified by high performance
      liquid chromatography and subjected to methanolysis. Fatty acids were analyzed by
      capillary gas liquid chromatography. In the intact retina and in the neural
      retina, the alkylacyl-glycero-3-phosphocholine and alkenylacyl-glycero-3
      phosphocholine comprise 1.2% and 1.5%, respectively, of the total choline
      phosphoglycerides, whereas the rod outer segments contain twice the proportion of
      the precursor of platelet-activating factor and no detectable plasmalogens. On a
      mole percent basis, arachidonic acid was highest in the neural retinal
      alkenylacyl-glycero-3-phosphocholine (27%), 18% in the alkylacyl-glycero-3
      phosphocholine and only 5% in the diacyl-glycero-3-phosphocholine. However,
      alkylacyl-glycero-3-phosphocholine from rod outer segments was enriched in
      docosapentaenoic acid (18%) while arachidonic acid was in the 3-4% range. Our
      results suggest that, in the neural retina, alkyl-arachidonoyl-glycero-3
      phosphocholine is a source of both platelet-activating factor and of arachidonic
      acid which may be a substrate for both prostaglandins and lipoxygenase
      metabolites during an inflammatory episode and may contribute to the retinal
      pathology.

PMID- 8156826
TI  - Preliminary characterization of a transformed cell strain derived from human
      trabecular meshwork.
AB  - Cells isolated from the trabecular meshwork (TM) of a male glaucoma patient were
      transformed by transfection with an origin defective mutant of SV40 virus.
      Transformation dramatically increased the growth rate of these cells (designated
      HTM-3 cells), allowing biochemical and pharmacological characterization. The HTM
      3 cells had cytoskeletal components that were reported to be present in TM tissue
      and non-transformed TM cells. Vimentin, tubulin and smooth muscle specific alpha
      actin, but not desmin, were localized in these cells by immunocytochemistry. The
      extracellular matrix components collagen types I, III and IV, fibronectin and
      laminin were found in HTM-3 cells as well as their non-transformed parental
      cells. As predicted, the protein profile of the HTM-3 cells revealed by two
      dimensional gel electrophoresis was different from that of the non-transformed
      cells, probably due to the enhanced growth characteristics of these cells.
      Furthermore, HTM-3 cells had various intracellular second messenger systems that
      responded to pharmacological agents. Forskolin, prostaglandin E2, beta-adrenergic
      and adenosine A2 agonists stimulated the adenylyl cyclase in these cells, whereas
      muscarinic, serotonergic, dopaminergic and other agonists were ineffective.
      Sodium nitroprusside increased the intracellular concentration of cGMP,
      demonstrating the presence of a functional guanylyl cyclase. Phospholipase C
      activity in these cells was also detected. Muscarinic agonists, histamine and
      bradykinin, but not adrenergic, serotonergic agonists or prostaglandins,
      increased phosphoinositide turnover. These drug responses of HTM-3 cells agree
      with published data on primary TM cells and TM tissues, suggesting that the
      transformed cells may be a valid substitute for certain pharmacological studies
      of TM.

PMID- 8156827
TI  - Catalytic subunit isoforms of mammalian lens Na,K-ATPase.
AB  - To identify the Na,K-ATPase isoforms present in the mammalian lens, seven
      antisera were prepared to selected peptide sequences of the catalytic (alpha)
      subunit. Three antisera were prepared to peptide sequences at the N-terminus of
      the three sequenced rat alpha isoforms. There is < 53% sequence homology among
      the isoforms in this region. Three antisera were prepared to peptide sequences at
      the ouabain binding site in the extracellular loop between membrane spanning
      sequences 1 and 2 of the sequenced rat alpha isoforms; sequence homology among
      the isoforms in this region is < 69%. An antiserum was also prepared to the
      carboxyl terminal region of the alpha 2 rat isoform. The sequenced isoforms (rat
      and human) in this region are > 94% homologous. The results from stains of
      Western blots of SDS-PAGE separations of lens membranes are presented. Alpha 1 is
      the predominant isoform of the epithelium. It is not found in cells of the
      central epithelium but is present in cells located more toward the equator. Alpha
      3 is the catalytic subunit of the central 43% of the epithelium. The lens fiber
      cell membranes have a catalytic subunit that is related to the alpha 2 isoform.
      In the fiber cell a 98-100 kDa band stains with the antiserum to the alpha 2 N
      terminus and the antiserum to the alpha 2 ouabain site. The antiserum to the
      alpha 2 C-terminus does not stain the 98-100 kDa band. (Preliminary reports of
      these results were presented at the 1992 and 1993 meetings of the Association for
      Research in Vision and Ophthalmology).

PMID- 8156829
TI  - Basic and clinical considerations in the use of xenografts.

PMID- 8156828
TI  - The combined effects of diabetes and ionising radiation on the rat retina: an
      ultrastructural study.
AB  - The combined effect of STZ-diabetes and ionising radiation on the rat retina was
      investigated. Wistar rats, which had been diabetic for 6 months, were irradiated
      with a single dose of x-rays (1500 cGy) and the ultrastructural effects evaluated
      at 4-10 mths post-irradiation. At 4 months post-irradiation, the outer nuclear
      layer of the retina was greatly reduced in thickness and the photoreceptor outer
      segments were disorganised and reduced in length. In addition, the nerve fibre
      layer contained many cytoid bodies and there were many redundant basement
      membrane tubes throughout the inner retina. By 6 months post-irradiation, the
      photoreceptor cells were virtually absent, bringing the external limiting
      membrane into close apposition to the RPE. Throughout large areas of the outer
      retina, RPE cells were hypertrophic and some had proliferated into the inner
      retina. In many regions, proliferating retinal capillaries were observed within
      the RPE layer, and at 8 months post-irradiation, some vessels extended into the
      inner retina accompanied by RPE cells. At 10 months post-irradiation, the RPE was
      atrophic and degenerative with retinal glial cells coming into contact with
      Bruch's membrane. In some areas, the glia which had breached Bruch's membrane had
      invaded the underlying choroid. Where glial cells contacted the
      choriocapillaries, the vessels assumed the appearance of retinal vessels with
      plump endothelia and no fenestrations. This study has described a progressive
      inner retinal ischemia, with cytoid bodies, capillary non-perfusion and general
      atrophy of the inner retina intensifying markedly with increasing post
      irradiation time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156830
TI  - The impact of managed care on dermatology.
AB  - The goal of managed care is to find the most effective mix of the factors of
      production to provide quality care to its members. The aforementioned information
      on the impact of managed care on dermatology suggests that the future of
      dermatology need not be bleak. The supply of dermatologists in the nation is far
      more consistent with the demand of classic MCOs for dermatologists than for
      almost all other specialties. In addition, any form of health care reform that
      increases access to health care for the uninsured and underinsured will increase
      the demand for dermatologic care. Similarly, a well-functioning managed care plan
      will move to establish the boundary line between skin care by PCPs and
      dermatologists in a consensual, objective, and mutually respectful process. The
      attempt to define this boundary will give added impetus to the development of
      outcomes measurement and management in managed care and serve to advance the
      interests of all parties concerned, including the patient. A well-defined
      boundary line between care appropriately rendered by PCPs and that provided by
      dermatologists will result in dermatologists treating a higher severity of
      illness--the cases for which dermatologists were trained to treat. The higher
      level of severity of illness could be associated with a higher level of
      professional satisfaction. Similarly, capitated arrangements between
      dermatologists and PCPs create incentives for cooperative education and
      communication initiatives between both parties to define appropriate ranges of
      care and referral timing. Where capitated arrangements do not exist, it is also
      important to define such appropriate ranges of care.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8156831
TI  - [The prevention of insulin-dependent diabetes mellitus].

PMID- 8156832
TI  - [Assessment of the therapeutic effect in acute myelogenous leukemia].

PMID- 8156833
TI  - [A new insulin-sensitivity index for the population-based study].
AB  - This paper suggests a new simple insulin-sensitivity index, the reverse of
      fasting plasma glucose and insulin product, which is significantly correlated
      with the insulin-sensitivity index determined by euglycemic insulin clamp
      technique (insulin mediated glucose disposal rate, M value) in 320 subjects of
      Americans including two races (r > 0.7, P = 0.0001). The analysis of 874 cases
      Chinese showed that the insulin-sensitivity (IS) evaluated by this new index in
      Chinese was similar to that determined by insulin clamp in Americans: If the IS
      in subjects with normal glucose tolerance defined as 1.0, then the IS in subjects
      with impaired glucose tolerance in Chinese and in Americans was 0.61, 0.62 (Pima
      Indians), 0.71 (Caucasians) and in diabetic Chinese and Americans was 0.57 and
      0.53 (Pima Indians and Caucasians) respectively. Thus, it indicated this new
      index is fit for the evaluation of IS in Chinese population.

PMID- 8156834
TI  - [Hyperinsulinemia in obesity and diseases of internal medicine].
AB  - We analysed fasting serum insulin levels and its correlation with common internal
      medical diseases in 91 cases with obesity (BMI > 24) and that in 76 nonobese
      cases. The mean fasting serum insulin level in obese group was higher
      significantly than that in nonobese group (P < 0.001). The incidences of
      hypertension, coronary heart disease, cerebrovascular disease, non-insulin
      dependent diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, combined
      hyperlipidemia and serum low level of HDL-C in obese group were also higher
      significantly than that in nonobese group (P < 0.05 and < 0.01 respectively). The
      main cause of many medical diseases coexisted with obesity is hyperinsulinemia.
      We think that the first choice of therapy to this kind of diseases should be to
      reduce the body weight and to decrease the insulin resistance.

PMID- 8156835
TI  - [The clinical significance of measuring plasma ionized calcium concentration].
AB  - Using selective electrode to measure the concentrations of plasma ionized calcium
      (ICa) in 222 normal volunteers and 329 patients which included seven kinds of
      diseases: hyperparathyroidism, overdose of AT10, cancer, hypoparathyroidism,
      alkalosis, acidosis and hypoalbuminemia was reported. The results demonstrated
      that this method was rapid, sensitive and reproducible. The concentration of
      plasma ICa can reflect the calcium metabolism and its disturbance in patients
      with hyperparathyroidism, hypoparathyroidism, alkalosis, acidosis and
      hypoalbuminemia precisely, so ICa assay was much better than total calcium
      measurement.

PMID- 8156836
TI  - [140 cases of acute leukemia caused by bimolane].
AB  - The cooperative group included 18 provincial and district hospitals. A
      retrospective study was carried out on 140 cases of therapy related leukemia
      (TRL) caused by bimolane (BML) for psoriasis from 1984 to 1992. This series of
      BML-TRL consists of 90 male and 50 female patients. 87.1% of them were from 20 to
      50 years old. Annual incidence varied from 4 to 24 cases, and was maintained at
      this level through the period from 1986 to 1991 without any declining tendency.
      The average time interval between BML administration and diagnosis of leukemia
      was 46 months. 138 cases were diagnosed as ANLL and 2 cases were suspected of
      having ALL. Subtype frequency was shown as follows: M3 > M2 > M5 > M4 > M1 > M6.
      67.1% of the patients had a low peripheral white blood cell counts (< 5 x
      10(9)/L). 116 patients received chemotherapy. A 26.7% remission rate was obtained
      with 18.1% complete remission and 8.6% partial remission. A 115 day median
      survival was calculated through a follow up survey of 95 patients. Finally, we
      concluded that: (1) This has been the largest group of non-cancer-therapy-related
      leukemia patients ever reported. This type of leukemia is characterized by a
      shorter latent period, higher remission rate less incidence of myelodysplastic
      syndrome and more frequent occurrence of leukopenia, as compared with other types
      of TRL. BML is supposed to be a strong leukemia-causing cytotoxic agent. Use of
      this drug in psoriasis and other benign diseases is not recommended.

PMID- 8156837
TI  - [A study on cellular differentiation and antigen receptor gene rearrangement in
      lymphoid malignancies].
AB  - Cellular differentiation origin and genotype of IgH and TCR gamma, delta gene
      rearrangement in 42 cases of lymphoid malignancies were studied by using
      immunoenzymatic method with monoclonal antibodies (McAbs) and polymerase chain
      reaction (PCR) technique respectively. The results suggested that among the 23
      cases, in which malignant cells expressed B-lineage cell surface markers, 20
      showed IgH gene rearrangement and 11 had TCR gamma gene rearrangement and/or TCR
      delta gene deletion. All the 11 cases expressed T-lineage cell differentiation
      antigens were found to have TCR gamma and TCR delta gene rearrangement or
      deletion and only one had IgH gene rearrangement. Double rearrangement of IgH and
      TCR gamma genes were detected in all the 3 cases of T.B double-phenotype ALL. In
      the cases, in which malignant cells did not express any lineage specific
      antigens, 4/5 had TCR gamma gene rearrangement, but all failed in IgH gene
      rearrangement. The relation of cellular differentiation origin and rearrangement
      of antigen receptor genes with clinical manifestations was also discussed.

PMID- 8156838
TI  - [Diagnosis of subclinical hepatic encephalopathy: a parallel and comparative
      study between the evoked potentials and the performance psychometric tests].
AB  - The authors report the results of a parallel study between the three kinds of
      evoked potentials (EP) i.e. visual, brainstem auditory and somatosensory evoked
      potentials (VEP, BAEP and SEP) and psychometric tests in 30 posthepatitic
      cirrhotic patients. The results were compared with those from 20 peptic ulcer
      patients in healing stage. Psychometric tests were abnormal in 65.5% of the
      cirrhotic and in none of the peptic ulcer patients. The three kinds of evoked
      potentials were abnormal in 58.6% of the cirrhotic patients and in 5% of the
      peptic ulcer patients. The VEP, BAEP and SEP was abnormal in 13.3%, 10% and 50%
      of the cirrhotics respectively. The results of this study showed: of the three
      kinds of evoked potentials, SEP is the most sensitive one. The evoked potentials
      and the performance psychometric tests are complementary in the diagnosis of
      subclinical hepatic encephalopathy.

PMID- 8156839
TI  - [Intravenous thrombolysis with domestic urokinase in 40 cases of acute myocardial
      infarction].
AB  - Thrombolytic therapy with intravenous domestic urokinase was carried out within 6
      hours after onset in 40 cases of acute myocardial infarction from Feb. 1991 to
      Dec. 1992, the age of patients being 52.5 +/- 8.4 (37-74) years. The overall
      reperfusion rate was 65.0%; the reperfusion rate within 3 hours was 78.3% (18/23)
      and from 3 to 6 hours 47.1% (8/17) (P < 0.05). The incidence of reperfusion
      arrhythmia was 73.1%. Reinfarction occurred in 3 and acute allergy in 2 cases. 3
      other cases developed ventricular fibrillation within 2 hours after onset. After
      prompt successful defibrillation, thrombolytic therapy was instituted and 2 cases
      had reperfusion. No marked bleeding and mortality were observed in all of our
      cases.

PMID- 8156840
TI  - [Clinical and pathological characteristics of Helicobacter pylori-associated
      chronic gastritis].
AB  - To define the clinical and pathological characteristics of Helicobacter pylori
      associated gastritis, 173 patients with chronic gastritis, including 99 Hp
      positive and 74 Hp-negative patients were studied. We found that there were no
      significant differences between Hp-positive and Hp-negative patients with regard
      to clinical symptoms, gastric acid secretion and serum basal gastrin level,
      whereas the grades of chronic gastritis and active gastritis were markedly higher
      in Hp-positive patients. 91.2% of patients with active gastritis had evidence of
      Hp infection. With the increase in Hp density, the proportion of high grades (II
      and III) gastritis tended to increase, especially the severe active gastritis. In
      addition, glandular atrophy and intestinal metaplasia in antral mucosa were
      significantly commoner in Hp-positive patients. There were no significant
      differences between the two groups in duodenogastric reflux rate, but the reflux
      rate over moderate degree in Hp-positive patients (19.59%) was somewhat lower
      that in Hp-negative patients (36.36%) (P = 0.09).

PMID- 8156842
TI  - [Streptococcal toxic shock syndrome].

PMID- 8156841
TI  - [Allergic granulomatous angiitis].
AB  - Allergic granulomatous angiitis (AGA) is a rare disease, which varies in clinical
      manifestation. The clinical course includes three stages. In the first stage most
      of the patients show symptoms of respiratory disease, 82 per cent of the patients
      has asthma and 88 per cent chronic rhinitis. In the second stage there is blood
      eosinophilia and in the last stage involvement of multiple organs. The etiology
      is not yet clear. Since 1982 four cases of AGA have been encountered in PUMC
      Hospital, but they were all diagnosed after 1988. All were male and aged 36-54
      years. Two of them had asthma history and three enlargement of liver and
      proteinuria, ECG showed heart block in two, all four had neuromuscular and
      cutaneous involvement and elevated blood eosinophil with absolute number ranging
      from 1254 to 8104/mm3. Biopsy from different sites showed panangiitis associated
      with eosinophil infiltration and/or granulomatosis formation. All were sensitive
      to prednisone therapy with or without CTX after treatment the absolute eosinophil
      count in the four patients was less than 1000/mm3 and the symptoms alleviated.

PMID- 8156843
TI  - [Efforts to avoid misdiagnosis of pulmonary embolism].

PMID- 8156844
TI  - [The role of the assessment of pulmonary function tests in the diagnosis and
      treatment of internal medical diseases].

PMID- 8156845
TI  - [Analysis of the misdiagnoses of obliterative pulmonary hypertension].
AB  - In order to reduce the misdiagnostic rate of obliterative pulmonary hypertension
      (OPH), the clinical data was analysed of 126 cases of OPH, including 83 cases of
      unexplained pulmonary hypertension (UPH) and 43 cases of thromboembolic pulmonary
      hypertension (TEPH). The results showed that the misdiagnostic rate of UPH and
      TEPH was 93.98% and 79.07% respectively, with a total misdiagnostic rate of
      88.89%. UPH was frequently misdiagnosed as congenital heart disease (63.86%),
      valvular heart disease (13.5%) and coronary heart disease (9.64%). TEPH was
      usually misdiagnosed as cardiomyopathy (37.21%), coronary heart disease (18.61%),
      and valvular heart disease (18.61%). The possible causes of misdiagnosis were
      discussed.

PMID- 8156846
TI  - [Observations on serum digoxin-like immunoreactive substances in patients with
      cor-pulmonale].
AB  - The level of endogenous digoxin-like immunoreactive substances (DLIS) was
      determined with RIA in 27 patients with cor-pulmonale and 10 normal subjects as
      controls. The results showed that the concentration of serum DLIS was 0.51 +/-
      0.18 ng/ml in the controls, 0.82 +/- 0.24 (P < 0.05), 1.45 +/- 0.51 (P < 0.001),
      and 2.31 +/- 1.22 ng/ml (P < 0.001) in the patients groups with cardiac function
      grade II (9 cases), III (10 cases) and IV (8 cases) respectively. It has been
      reported that both endo- and exogenous digoxin-like substances have the same
      function. Cor-pulmonale patients with heart failure who are treated with digoxin
      tend to have toxic reactions. We consider the increase in serum endogenous DLIS
      as the cause. It is suggested that the dosage of digoxin, if it must be used,
      should be individualized and the serum level monitored if possible, so as to
      achieve best therapeutic effects with smaller doses.

PMID- 8156847
TI  - [Clinical significance of changes in plasma renin-angiotensin aldosterone system
      in patients with high altitude pulmonary edema].
AB  - Plasma levels of renin activity, angiotensin II and aldosterone were determined
      in 16 patients with high altitude pulmonary edema (HAPE) with radioimmunoassay
      and compared with those in the controls including 9 patients with high altitude
      acute response (HAAR) and 14 health subjects. All of them arrived recently in
      Lhasa, a place with an altitude of 3,658 m. The results showed that the
      concentration of plasma renin activity, angiotensin II, and aldosterone was
      significantly increased (P < 0.05-0.001) in patients with HAPE and higher than
      that in the controls. It is suggested that the increase plays a role in the
      development of pulmonary edema in patients with HAPE.

PMID- 8156848
TI  - [Antianginal and lipid lowering effects of oral androgenic preparation (Andriol)
      on elderly male patients with coronary heart disease].
AB  - Sixty-two elderly men with coronary heart disease (CHD), 54 of them also
      suffering from hyperlipidemia, were treated with a new oral androgenic
      preparation (Andriol) through crossover study. The results showed that after oral
      Andriol administration for one month, serum estradiol/testosterone (E2/T) ratio
      was reduced, (P < 0.05) symptom of angina pectoris was relieved (total effective
      rate, 77.4%), signs of myocardial ischemia in ECG and Holter monitoring were
      improved (total effective rate, 68.8% and 75% respectively), serum total
      cholesterol (TC) and triglyceride (TG) levels were reduced dramatically (both P <
      0.001) and the serum level of high density lipoprotein cholesterol (HDL-ch) was
      increased (P < 0.05), but the blood levels of apolipoprotein-AI (APO-AI) and B
      (APO-B) remained unchanged. No significant side effect of Andriol was observed.

PMID- 8156849
TI  - [A study of gastric mucosal blood flow of peptic ulcer, chronic gastritis and
      gastric carcinoma].
AB  - Gastric mucosal blood flow (GMBF) was studied in of 187 cases of peptic ulcer,
      chronic gastritis and gastric carcinoma with Laser Doppler Flowmetry (PF2).
      Results showed that GMBF in active ulcer (n = 68) was significantly slower than
      that in normal subjects (51.8% of normal value). GMBF in chronic atrophic
      gastritis (CAG) was significantly lower than that in chronic superficial
      gastritis (CSG). GMBF in gastric carcinoma was obviously slower than that in
      benign active ulcer as well as CAG and CSG. GMBF might be of help in the
      differential diagnosis of malignant or benign ulcer of stomach.

PMID- 8156850
TI  - [Changes of the binding capacity of sex hormone binding globulin in patients with
      hyperthyroidism before and after antithyroid therapy].
AB  - We studied the change of the binding capacity of the sex hormone binding globulin
      (SHBG-BC) and correlated it with the serum level of thyroid hormone and sex
      hormone in 17 patients (10 males and 7 female) with hyperthyroidism before and
      during the 16 weeks of antithyroid treatment. The serum TT4, TT3, FT4I level and
      SHBG-BC were significantly elevated before treatment compared to normal adults.
      After the treatment with antithyroid drugs, serum SHBG-BC decreased significantly
      at 2nd weeks in female (from 312.9 +/- 39.6 to 205 +/- 18.6 nmol/L, P < 0.05) and
      at 8th weeks in male (from 155.7 +/- 18.6 to 109.7 +/- 7.9 nmol/L, P < 0.05). It
      continued to decrease to normal range (78.6 +/- 7.3 vs 65.0 +/- 24.1 nmol/L, P >
      0.05) at 8th weeks in female, but was still higher than normal range (107.4 +/-
      7.2 vs 41.5 +/- 10.2 nmol/L, P < 0.001) even at 16th weeks in male. The change of
      SHBG-BC was significantly positively correlated to the serum concentration of
      TT4, TT3 and FT4I(P < 0.001). In male patients the serum testosterone (T) level
      decreased from a high level of 41.9 +/- 6.2 nmol/L before treatment to 25.4 +/-
      3.4 nmol/L at 8th weeks (P < 0.05) and to 19.8 +/- 2.8 nmol/L at 16 weeks which
      was in normal range. The decrease of serum T level was also positively correlated
      to the changes of SHBG-BC (P < 0.0001). The serum estradiol (E2) level of female
      patients was in the upper normal range before the antithyroid treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8156851
TI  - [Characterization of morphologic, cytochemical and immunological features in
      myeloperoxidase negative acute myeloid leukaemia].
AB  - Ten cases of acute myeloperoxidase-negative myeloid leukaemia (AML) were
      reported. They had no typical mopholocid negative for lymphocic features and were
      negative antigens. However 5 cases were positive for NSE/NaF stain. 9 of the 10
      cases expressed more than one myeloid antigens. The authors are of the opinion
      that it is very difficult to diagnose myeloperoxidase-negative AML and
      combination of cytochemical and immunological techniques is recommended in this
      respect.

PMID- 8156852
TI  - [Preparation of monoclonal antibody against basic glutathione S-transferase and
      its clinical application].
AB  - Balb/c mice were immunized with basic glutathione s-transferase (B-GST) prepared
      from human liver and the monoclonal antibody against B-GST was purified. Serum B
      GST level was measured in 234 patients with various types of viral hepatitis with
      solid radioimmuno-sandwich assay and the value in 70 donors (4.19 +/- 4.42 ng/ml)
      used as control. The serum B-GST level in 117 cases with acute icteric hepatitis,
      85 cases with chronic active hepatitis and 32 cases with severe hepatitis were
      8.6, 8.4 and 5.9 times higher than that of the controls respectively. At the same
      time, serum alanine amino-transferase (ALT) activity in patients with various
      types of viral hepatitis were 6.8, 3.1 and 2.4 times higher respectively. These
      results showed that the change of serum B-GST level was more prominent than that
      of ALT activity. In addition, the change of B-GST in 35 patients with CAH and 13
      with severe hepatitis were serially observed. Serum B-GST level persisted at high
      level for a long time in most of the patients, while serum ALT activity soon
      became normal. It is shown that serum B-GST level is more valuable than ALT in
      estimating chronic and severe liver damage.

PMID- 8156853
TI  - [Changes in the activity of natural killer cells in lung diseases and related
      influencing factors].

PMID- 8156855
TI  - Computerised campimetry with static dark-on-bright stimuli.
AB  - Perimetric examination of the central visual field with low contrast static dark
      on-bright stimuli on a video display unit (VDU) is described. Threshold detection
      sensitivities to such dark stimuli are determined in normal as well as
      pathological central visual fields of glaucomatous, diabetic and neuro-ophthalmic
      patients. The static dark (light decrement type) stimuli on VDU seem capable of
      documenting the central visual field defects with high accuracy and revealing the
      field loss missed by conventional luminous (light increment type) stimuli of
      equal size and duration. In this report, the author presents examples from his
      new perimetric approach.

PMID- 8156854
TI  - Ocular myasthenia gravis. A critical review of clinical and pathophysiological
      aspects.
AB  - Myasthenia gravis (MG) is probably the best studied autoimmune disease caused by
      autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular
      junction, subsequently leading to abnormal fatigability and weakness of skeletal
      muscle. Extraocular muscle weakness with droopy eyelids and double vision is
      present in about 90% of MG patients, being the initial complaint in about 50%. In
      approximately 20% of the patients the disease will always be confined to the
      extraocular muscles. The single most important diagnostic test is the detection
      of serum antibodies against AChR which is positive in 90% of patients with
      generalized MG, but only in 65% with purely ocular MG. Electromyographic studies
      and the Tensilon test are of diagnostic value in clear-cut cases, but may be
      equivocal in purely ocular myasthenia, especially the latter not rarely producing
      false-positive results. Treatment response to corticosteroids and anti
      cholinesterase agents is satisfactory in many patients with ocular MG, however
      other immunosuppressive drugs may also be needed. Pathogenetically relevant steps
      of the underlying autoimmune process have been elucidated during the last few
      years; nevertheless a number of questions remain open, especially what starts off
      the autoimmune process, and why are eye muscles so frequently involved in MG?

PMID- 8156856
TI  - Growth characteristics of human lens epithelial cells in culture. Effect of media
      and donor age.
AB  - The effect of different concentrations of fetal calf serum (FCS) on the
      proliferative capacity of human and bovine lens epithelial cells in culture was
      evaluated. The effect of donor age on the maximum number of passages achieved
      using thirty eight individual cultures was also studied. The donor ages ranged
      from 1-88 years. Fifteen percent FCS was found to be the optimum concentration
      for both human and bovine cells. The two cell types demonstrated very similar
      responses across the spectrum of concentrations used. Correlation analysis
      revealed a significant (p < 0.05) negative correlation between donor age and
      maximum number of cell passages achieved.

PMID- 8156857
TI  - Terson's syndrome in a patient with acute promyelocytic leukemia on all-trans
      retinoic acid treatment.
AB  - The syndrome of vitreous hemorrhage in association with any form of intracranial
      bleeding is known as Terson's syndrome. Acute promyelocytic leukemia (APL)
      constitutes 5% to 15% of cases of acute nonlymphocytic leukemias, in which
      hemorrhagic diathesis often occurs and results in a rapid fatal outcome. In this
      report we describe a patient with APL who developed cerebral bleeding in
      association with bilateral subhyaloid and vitreous hemorrhages consistent with
      Terson's syndrome while she was on all-trans retinoic acid induction therapy.

PMID- 8156858
TI  - Tight versus loose scleral flap closure in trabeculectomy surgery.
AB  - Thirty-two consecutive trabeculectomy patients were randomized to receive a tight
      scleral flap closure (15 eyes) with postoperative laser suture lysis, or a loose
      scleral flap closure (18 eyes) to determine differences in the surgical results.
      Three months postoperatively no statistical difference in intraocular pressure
      (loose closure 15.1 +/- 3.3 mm Hg, tight closure 15.0 +/- 3.6 mm Hg, p > 0.05) or
      number of glaucoma medicines (loose closure 1.6, tight closure 1.3, p > 0.05)
      existed between treatment groups. In the early postoperative period, no
      statistical difference between groups was observed in the anterior chamber depth,
      visual acuity or intraocular pressure (p > 0.05). Laser suture lysis was
      performed without complication in nine patients with a statistically significant
      reduction in intraocular pressure (p < 0.01). This study suggests, by the
      technique used, that no obvious benefit exists in using a tight versus a loose
      scleral flap closure when performing a trabeculectomy.

PMID- 8156859
TI  - Intracapsular and extracapsular pseudophakic endophthalmitis: a comparison.
AB  - A hundred and four cases of post cataract endophthalmitis with positive vitreous
      cultures are discussed. Functional results depend largely on the infecting agent
      but even after Staphylococcus epidermidis infections some eyes may be lost.
      Although post lens surgery endophthalmitis carries the best prognosis in the
      endophthalmitis group, 40% of the eyes are lost, sometimes caused by a delayed
      vitrectomy decision. Comparing intracapsular and extracapsular lens surgery two
      big differences were noted: (1) the bacteriology, and (2) the functional results.
      The bacteriological spectrum of the ICCE was composed of 1/3 of S. epidermidis,
      70% of Gram + cocci and 80% of Gram+organisms. After extracapsular lens
      extraction the majority of cases (60%) were caused by S. epidermidis (statistical
      significance 0.01). The difference in functional result is explained by the
      difference in bacteriology: if only the S. epidermidis cases are compared,
      functional results between both categories are nearly equal. ECCE seems to make
      the eye more vulnerable to infection by a low virulent agent.

PMID- 8156860
TI  - Pain management for children with insulin-dependent diabetes.

PMID- 8156861
TI  - Teaching infection control in blood glucose monitoring.

PMID- 8156862
TI  - Revisiting nurse knowledge about diabetes: an update and implications for
      practice.
AB  - This study attempted to ascertain the diabetes knowledge level of nurses in a
      university medical center, to describe correlates of nurse knowledge, and to
      compare levels of diabetes knowledge between nursing units. A convenience sample
      of staff nurses (n = 99) from six inpatient units and an ambulatory care center
      volunteered to complete a previously developed, 45-item questionnaire testing
      their knowledge of basic concepts about diabetes mellitus. Analysis of variance,
      comparing the nursing units, indicated a significant difference between units (P
      = .04) on the knowledge questionnaire. In a 4-step, hierarchical, multiple
      regression analysis, variables related to how competent the nurses felt in caring
      for diabetic patients and the number of diabetic patients cared for in the past
      month explained 28% of the variance in diabetes knowledge. Although this study
      corroborates earlier findings, questions still remain concerning the general
      adequacy of nurses' knowledge about diabetes.

PMID- 8156863
TI  - Assessing the diabetic foot: plantar callus and pressure sensation.
AB  - The purpose of this study was to explore the relationship between the loss of
      protective pressure sensation in the foot and the formation of plantar calluses,
      two well-known precursors of plantar ulceration, in adults with diabetes referred
      to an outpatient diabetes education program. Pressure sensation testing was
      performed using Semmes-Weinstein monofilaments. Foot inspection included the
      identification and measurement of plantar calluses. Using the Wilcoxon Rank Sum
      test, groups categorized as sensitive (n = 67) and insensitive (n = 35) were
      compared on callus formation. The groups had equivalent numbers, areas, and
      thickness of calluses. The high prevalence of calluses in both sensitive and
      insensitive groups suggests that additional factors such as age-related changes
      in the foot and routine footwear must be included in risk assessment of the
      diabetic foot and in consideration of preventive interventions.

PMID- 8156864
TI  - The impact of the Trial Coordinator in the Diabetes Control and Complications
      Trial (DCCT). The DCCT Research Group.
AB  - The Diabetes Control and Complications Trial (DCCT) is a multicenter, randomized
      clinical trial studying the effects of two different diabetes regimens on the
      development and progression of early vascular complications in persons with
      insulin-dependent diabetes mellitus (IDDM). All of the centers have a Trial
      Coordinator. We administered a self-report questionnaire to each center to
      document the different activities for which the Trial Coordinator assumed
      responsibility in successfully orchestrating the trial. All Trial Coordinators
      were responsible primarily for recruitment, screening, medical management,
      education and training, and adherence and administration. Although documentation
      indicated that the Trial Coordinator was responsible for all of the above
      activities, the original applications reflected that very few of the Principal
      Investigators anticipated such a wide variety of duties. A Trial Coordinator was
      named in only 13 of the 21 applications and of these, only 6 actually assumed the
      position. This study points out the need to develop a means to define
      characteristics, background, and training appropriate for candidates for a Trial
      Coordinator position in future studies.

PMID- 8156865
TI  - Third-party reimbursement for home care of clients with diabetes.
AB  - Home health care has increasingly become an integral component of the health care
      continuum for clients. The concept of providing care to a client in the home
      setting seems relatively straightforward. What has grown increasingly complex is
      the reimbursement structure under which services are provided. Adding to the
      complexity are the frequent changes in the regulations that govern the
      reimbursement for home care. This paper describes the current state of the third
      party regulations that govern the reimbursement for the client with diabetes
      receiving home care.

PMID- 8156866
TI  - Nursing case management: an innovative model of care for hospitalized patients
      with diabetes.
AB  - Cost, access, and quality are among the most pressing concerns facing the
      delivery of health care services in the 1990s. These issues are of particular
      concern for individuals with diabetes because of their high consumption level of
      health care resources. The purpose of this study was to evaluate whether a
      managed care approach could reduce the hospital stay while creating a balance
      between cost and quality of care.

PMID- 8156867
TI  - Identifying and treating common and uncommon infections in the patient with
      diabetes.
AB  - Patients with diabetes represent a unique group of individuals who appear more
      prone than others to developing infections. Several mechanisms have been proposed
      to explain the association between diabetes and infections. However, few
      conclusive studies exist and considerable debate continues regarding evidence for
      this predisposition. Despite this lack of documented proof, many health care
      practitioners acknowledge that a number of infections are overrepresented in
      patients with diabetes. Some of these infections appear to occur exclusively in
      patients with diabetes, especially patients who are poorly controlled. The
      presenting clinical features, causative organisms, and preferred treatment
      approaches will be discussed in this article for a variety of common and uncommon
      infections observed in patients with diabetes. In addition, the proposed
      predisposing factors will be addressed briefly.

PMID- 8156868
TI  - [Isolated lung transplantation. Analysis of 17 consecutive operations. Munich
      Lung Transplant Group].
AB  - 16 patients (nine men, seven women; mean age 45 [23-62] years) with end-stage
      pulmonary disease underwent lung transplantation, 14 unilateral, three bilateral
      (one bilateral retransplantation). The diagnoses were: emphysema (n = 5),
      idiopathic pulmonary fibrosis (n = 5), emphysema in alpha 1-antitrypsin
      deficiency (n = 1), mucoviscidosis (n = 1), drug-induced fibrosis (n = 1),
      chronic lung rejection after heart-lung transplantation (n = 1), secondary
      pulmonary hypertension with persistent ductus arteriosus (n = 1), sarcoidosis (n
      = 1) and chronic transplant failure after unilateral transplantation (n = 1).
      Eleven patients survived long-term (mean follow-up period 247 [8-585] days). Ten
      of these patients have been independent of additional oxygen after an average of
      8 months postoperatively, eight are physically active according to their age.
      Three patients died of reperfusion damage intraoperatively or in the early
      postoperative period. The two other patients died from septicaemia 5 1/2 and 7
      months postoperatively. It is concluded that lung transplantation in end-stage
      pulmonary disease provides the only therapeutic means with any expectation of
      physical rehabilitation.

PMID- 8156869
TI  - [Recurrent D-lactic acidosis with encephalopathy in a boy with short-bowel
      syndrome].
AB  - For two years after surgical small-intestine duplication a 9-year-old boy with
      the short bowel syndrome had recurrent acidosis which caused severe failure to
      thrive. During the acidotic crises he had behavioural disorders, unsteady gait,
      indistinct speech, lid raising weakness with vision paresis and occasional
      somnolence. These signs disappeared after the aciduria had been treated with high
      doses of bicarbonate. D-lactic acidosis was finally diagnosed by simultaneously
      determining D-lactate (8.9 mmol/l [normal < 0.5]) and L-lactate (1.4 mmol/l
      [normal < 1.78]) during an episode of aciduria (pH 7.3, base excess -11.8
      mmol/l). Further acidotic crises were prevented by a carbohydrate-modified diet,
      on which he gained 8 kg in one year.

PMID- 8156870
TI  - [Minimally invasive thoracic surgery].

PMID- 8156871
TI  - [Mediator mechanisms in the pathogenesis of glomerulonephritis].

PMID- 8156872
TI  - [Does analgetic intolerance exist?].

PMID- 8156873
TI  - [The expert witness and his testimony].

PMID- 8156874
TI  - [Decubitus ulcer].

PMID- 8156875
TI  - [Bloodletting and blood donation].

PMID- 8156876
TI  - [Indications for laparoscopy in internal medicine].

PMID- 8156877
TI  - [Force-feeding in geriatric care].

PMID- 8156878
TI  - [Ambulatory treatment without antibiotics in children with fever].

PMID- 8156879
TI  - [Thrombolysis in acute myocardial infarct. What can further multicentric studies
      hope to accomplish?].

PMID- 8156880
TI  - [Diagnosis of phlebothrombosis using color-coded duplex sonography. A prospective
      comparison with phlebography].
AB  - In a prospective study the reliability of colour-coded duplex-sonography (CCDS)
      and phlebography in the diagnosis of deep leg and pelvic vein thrombosis was
      compared. In 82 consecutive in- or out-patients (42 men, 40 women; mean age 53
      [19-86] years) with clinically suspected leg or pelvic vein thrombosis the
      results of 275 phlebographies (reference method) and 275 CCDS were compared on
      admission and during follow-up. The two methods were performed less than 6 hours
      apart. In the diagnosis of thrombosis the sensitivity of CCDS was 99%,
      specificity 80%. In 88% of all tests, the different thrombosis levels, as
      diagnosed by phlebography, were also demonstrated by CCDS. These data indicate
      that, if the clinical picture of suspected deep leg or pelvic vein thrombosis is
      unclear, CCDS should be done first. Phlebography should be performed only if the
      results of the former are inconclusive.

PMID- 8156881
TI  - [Physical complaints and subjective stress in working relatives].
AB  - This study was undertaken to determine the extent of physical complaints in
      relation to the degree of subjective burden sustained by those who care for ill
      relatives at home. The sampled group consisted of 114 carers (98 women, 16 men),
      average age 58 +/- 13 years, looking after relatives with various illnesses and
      various levels of care requirements. Extensive caring was needed by 48%. The
      complaints were documented on the Giessen Symptoms Form and the stress on the
      Domestic Care Scale. The extent of the symptoms compared with the general
      population was expressed by percentage ranking: PR > 50 (above-average extent of
      symptoms) and PR < or = 50 (average or below-average extent of symptoms). This
      sample revealed above-average extent of symptoms both for the overall stress (PR
      > 50: 70%; PR < or = 50: 30%, P < 0.001) as for limb aches (79 vs 21%, P <
      0.001), tendency to exhaustion (74 vs 26%, P < 0.001), stomach complaints (65 vs
      35%, P < 0.01) and cardiac symptoms (62 vs 38%, P < 0.02). The extent of symptoms
      was significantly related to the degree of stress. With less stress the
      relationship was similar to that in the general population (48 vs 52%), while
      moderate stress (71 vs 29%, P < 0.001) and especially marked stress (94 vs 6%, P
      < 0.001) caused a marked increase in symptoms.

PMID- 8156882
TI  - [Neutralizing antibodies against salmon calcitonin. The cause of a treatment
      failure in Paget's disease].
AB  - A 72-year-old woman with Paget's disease of the femur (increasing curvature of
      the femur in the last 20 years, lately with ever more pain on walking) was at
      first treated with salmon calcitonin, daily 400 IU nasally, for 2 years. As a
      result, alkaline phosphatase (AP) concentration fell from initially 703 U/l, to
      401 U/l after 7 months' treatment. An increase in AP concentration was first
      noted after 10 months of treatment, rising after 24 months to 688 U/l. The
      symptoms, initially having responded rather well to therapy, markedly progressed.
      In parallel, titres were recorded for binding (maximally 1:100) and neutralizing
      antibodies (neutralizing action maximally 75%) against salmon calcitonin. Because
      of the development of secondary resistance to salmon calcitonin the medication
      was changed to human calcitonin (100 IU daily, subcutaneously). This again
      resulted in a fall of the AP concentration (to 319 U/l), which remained
      essentially unchanged (401 U/l) over a period of 17 months on 100 IU human
      calcitonin three times weekly.

PMID- 8156883
TI  - [The differential diagnosis of nodular tumors of the hand].

PMID- 8156884
TI  - [The diagnosis and therapy of spontaneous pneumothorax].

PMID- 8156885
TI  - Buserelin.

PMID- 8156886
TI  - [Is there a characteristic sleep apnea heart?].

PMID- 8156887
TI  - [Long-term results following coronary catheter dilatation and bypass surgery].

PMID- 8156888
TI  - [Late relapse following Hodgkin's disease].

PMID- 8156889
TI  - [Continuing education and health work: a process under construction].

PMID- 8156890
TI  - [Management of continuing education: a reflection from a strategic perspective].

PMID- 8156891
TI  - [Mexico: identification of educational needs in health districts. The
      Netzahualcoyotl experience].

PMID- 8156892
TI  - [Continuing education and improvement of the family doctor and nurse in Cuba: the
      example of Pinar del Rio].

PMID- 8156893
TI  - [Brazil: training for the administration of basic health units in the health
      districts].

PMID- 8156894
TI  - [Continuing education for advanced training in health services administration:
      the experience in Nicaragua].

PMID- 8156896
TI  - [Conceptual contributions for the construction of monitoring methodologies for
      educational processes in health services].

PMID- 8156895
TI  - [The experience of continuing education at the Universidad del Valle and the
      local health systems of the city of Cali, Colombia].

PMID- 8156897
TI  - [Learning on the job: monitoring the educational process in a public health
      postgraduate program in Honduras].

PMID- 8156898
TI  - [Continuing education for the reorganization of health services in Bolivia: model
      constructed by successive approximations based on its monitoring].

PMID- 8156899
TI  - [The Dominican Republic: continuing education of the health team at the regional
      and local levels. National Commission on Continuing Education].

PMID- 8156900
TI  - [Evaluation of the effort toward continuing education of the local health team.
      Methodological field test in the canton of Perez Zeledon, Costa Rica].

PMID- 8156901
TI  - Stimulation of glucagon-like peptide-1 secretion by muscarinic agonist in a
      murine intestinal endocrine cell line.
AB  - Studies on the cholinergic regulation of intestinal L-cells have been focused on
      the release of enteroglucagon, but the signal transduction pathways were not
      defined. These were here investigated by using as index the release of
      immunoreactive glucagon-like peptide-1 (GLP-1) from the endocrine cell line STC
      1, that has been shown to contain proglucagon mRNA transcripts. Abundant GLP-1
      immunoreactivity was revealed in STC-1 cells at immunocytochemistry and by RIA.
      The cell content was 4927 +/- 689 pg/10(6) cells, as measured with antiserum 199D
      that recognizes specifically the C-terminal amidated forms of GLP-1. The
      secretion of GLP-1 over a 2-h incubation period amounted to 1.4 +/- 0.3% of the
      total GLP-1 cell content and was significantly increased by 10 microM forskolin
      and 100 nM 12-O-tetradecanoylphorbol 13-acetate to 206% and 574% of control
      values, respectively. The cholinergic agonist carbachol stimulated GLP-1
      secretion in a concentration-dependent manner, maximal release was observed at 1
      mM carbachol (228% of the control value). Binding of the muscarinic antagonist [N
      methyl-]scopolamine ([3H]NMS) on cell homogenates was time dependent, specific,
      and saturable. Scatchard analysis revealed one class of receptors (Kd, 14 pM;
      binding capacity, 20 fmol/mg protein). Carbachol (0.1 microM to 1 mM) dose
      dependently displaced [3H] NMS binding and increased the intracellular calcium
      concentration without modification of adenylate cyclase activity. The order of
      potency of different antagonists, showing a preferential affinity for M1, M2, and
      M3 muscarinic receptor subtypes, to inhibit [3H]NMS binding, the carbachol
      induced increase in intracellular calcium, and carbachol-stimulated GLP-1
      secretion, was as follows: atropine (nonselective) > 4-diphenylacetoxy-N
      methylpiperidine methiodide (M3) > pirenzepine (M1) > AF-DX 116 (M2). The results
      of the present study, therefore, demonstrate that secretion of GLP-1 induced by
      cholinergic agonist depends on muscarinic M3-subtype receptors in the endocrine
      intestinal cell line STC-1. This system may prove useful to study the cellular
      mechanisms of GLP-1 secretion.

PMID- 8156902
TI  - Specificity of retinoid receptor gene expression in mouse cervical epithelia.
AB  - Retinoids are powerful regulators of epithelial differentiation and are essential
      for its maintenance. Because retinoids are necessary for cervical epithelial
      differentiation, they have been used as chemopreventive agents of cervical
      dysplasia and neoplasia. We were interested in determining whether different
      cervical epithelial phenotypes express specific retinoid receptors. The cervical
      epithelium contains the two phenotypes, stratified squamous and simple columnar,
      which join at the squamocolumnar junction. In addition, the simple columnar
      epithelium undergoes squamous metaplasia in response to vitamin A deficiency.
      Therefore, the cervical epithelium is suitable to study the expression pattern of
      the retinoid receptors in the three phenotypes, simple columnar, stratified
      squamous, and squamous metaplastic, simultaneously. The distribution pattern of
      the major retinoic acid receptor (RAR) isoforms (alpha 1, alpha 2, beta 2, beta
      3, gamma 1, and gamma 2) and retinoid-X receptors (RXR alpha, -beta, and -gamma)
      was studied by in situ hybridization. At the tissue level, RAR alpha (1 and 2)
      and RXR (alpha and beta) transcripts and, to a lesser extent, RAR gamma (1 and 2)
      transcripts were associated with the cervical stratified squamous subjunctional
      epithelium. The simple columnar epithelium, which is highly responsive to vitamin
      A status, expressed high levels of RAR alpha (1 and 2), RAR beta (2 and 3), and
      RXR (alpha and beta) transcripts. Only RAR beta (2 and 3) and RXR (alpha and
      beta) transcripts were down-modulated by the condition of vitamin A deficiency
      and expressed less in squamous metaplastic foci than the simple columnar
      epithelium. RXR gamma was undetectable in all three cervical epithelia. At the
      cellular level, basal and suprabasal expression was found for RARs, and
      preferential localization of RXRs was seen in basal cells. RXRs are auxiliary
      proteins for a variety of other nuclear receptors with which they form
      heterodimers, including RARs. The fact that RXRs are mainly localized in basal
      and columnar cells of the cervix suggests the need for the regulation and
      diversity generated by potential heterodimeric interactions in these rapidly
      proliferating cells in vivo. The unique pattern of expression and localization of
      the RARs and RXRs in different cervical epithelial tissues and cell types
      supports the hypothesis that they perform specific functions in cervical
      epithelial differentiation. This is in contrast to the major isoforms of each
      RAR, which have similar patterns of expression in the different cervical
      epithelial phenotypes and cell types, suggesting a redundancy in function.

PMID- 8156903
TI  - Regulation of gonadotropin-releasing hormone gene expression by the excitatory
      amino acids kainic acid and N-methyl-D,L-aspartate in the male rat.
AB  - The glutamate analogs N-methyl-D,L-aspartate (NMA) and kainic acid are involved
      in the regulation of GnRH and LH release in mammals. It has recently been
      reported that the increase in GnRH release induced by NMA is accompanied by an
      increase in GnRH mRNA levels, as measured by in situ hybridization. In the
      present study we assessed the effects of NMA and kainic acid on cytoplasmic mRNA
      levels using the more quantitative solution hybridization/RNase protection assay.
      To address the mechanism responsible for these mRNA changes, we also examined
      changes in heteronuclear RNA transcripts as a reflection of gene transcription.
      Adult male rats were implanted with a jugular catheter, and 1-2 days later, NMA
      (14 mg/kg BW), kainic acid (2 mg/kg BW), both NMA and kainic acid, or saline
      vehicle were injected through the cannula. Rats were killed 15 min or 1 h later
      by decapitation, blood samples were collected for RIA of LH, brains were removed,
      and the preoptic area was dissected and frozen. Cytoplasmic and nuclear RNA were
      extracted and assayed separately by RNase protection assay. Treatment with NMA or
      NMA plus kainic acid resulted in significantly elevated cytoplasmic mRNA levels
      15 min and 1 h later compared to saline control values, with no differences
      between the two drug treatments observed. Kainic acid stimulated mRNA levels 1 h,
      but not 15 min after injection. Nuclear RNA transcripts were unaffected by all
      drug or vehicle treatments. As nuclear primary transcript levels presumably
      reflect GnRH gene transcription, and these levels are unaltered, the present
      study indicates that the regulation of GnRH gene expression by excitatory amino
      acids occurs at a posttranscriptional level. The increase in cytoplasmic GnRH
      mRNA levels also does not result from an increased translocation of the
      relatively large nuclear GnRH mRNA pool into the cytoplasm, because nuclear GnRH
      mRNA levels are also unchanged. Therefore, the elevation of cytoplasmic mRNA
      levels after excitatory amino acid treatment is probably due to an increase in
      mRNA stability.

PMID- 8156904
TI  - Thyrotropin (TSH)-induced receptor internalization in nonthyroidal cells
      transfected with a human TSH-receptor complementary deoxyribonucleic acid.
AB  - TSH-induced desensitization was studied in nonthyroidal cells expressing
      functionally active TSH receptors (TSHR). Chinese hamster ovary (CHO) cells and
      mouse NIH 3T3 cells were stably transfected with a human TSHR cDNA. Stimulation
      of the CHO-TSHR and NIH-TSHR cells with 10 mU/ml TSH resulted in a decreased
      sensitivity to a second TSH stimulation only in the NIH-TSHR cells. A decrease in
      TSH-induced cAMP was present within 1 h and coincided with a decreased binding of
      [125I]TSH. The half-maximal effect was observed after a 3- to 4-h stimulation
      with TSH, and exposure of cells to TSH for 20 h led to a 70-80% inhibition of
      cAMP formation. After withdrawal of TSH, cells regained full responsiveness to
      TSH after 6 h. Moreover, the desensitization effect observed in NIH-TSHR cells
      was not mimicked by forskolin and, therefore, was not mediated by cAMP.
      Stimulation of the CHO-TSHR cells with TSH did not result in a desensitization
      toward a second TSH stimulation, nor did it reduce the binding of [125I]TSH. This
      difference between the two cell lines might be explained by a higher turnover
      rate of receptors in the CHO cells. Indeed, incubation of cells with [125I]TSH
      showed a more efficient internalization of ligand in the CHO-TSHR cells compared
      to the NIH-TSHR cells. In summary, the homologous desensitization observed in
      TSHR-transfected NIH 3T3 cells appears to be the result of ligand-induced
      receptor down-regulation.

PMID- 8156905
TI  - Processing of chromogranin A by bovine parathyroid secretory granules: production
      and secretion of N-terminal fragments.
AB  - Chromogranin A (CgA) is a glycoprotein located in the secretory granules of
      multiple neuroendocrine tissues, including the parathyroid gland. Although the
      function of CgA is not known, a role has been proposed for CgA as a prohormone
      for biologically active peptides. Using 3H-CgA as a substrate for bovine
      parathyroid secretory granule extracts, we demonstrate a precursor product
      relationship between intact CgA and multiple N-terminal fragments of CgA. N
      terminal CgA fragments of mol wt 24, 26, and 33 k are generated in a time
      dependent manner in the presence of bovine parathyroid secretory granule enzymes.
      The generation of the 33 kilodalton (kDa) N-terminal CgA fragment is calcium
      dependent. In the presence of EDTA, intermediate CgA fragments of mol wt 36 and
      45 are generated. The effect of EDTA is reversible with added calcium. Based on
      immunodetection on Western blots, the 26 kDa N-terminal fragment of CgA is
      secreted by bovine parathyroid cells in a time and calcium-dependent manner in
      parallel with PTH and intact CgA. The secretion of the 26 kDa N-terminal fragment
      of CgA increases in response to low calcium incubation conditions and is
      suppressed by high calcium incubation conditions. We conclude that bovine
      parathyroid secretory granules contain enzymatic activity capable of processing
      CgA to multiple N-terminal fragments. The secretion of at least one N-terminal
      fragment (26 kDa) is calcium responsive. The physiological significance of CgA
      processing in parathyroid secretory granules is as yet unknown.

PMID- 8156906
TI  - Developmental regulation of glucocorticoid-mediated effects on extracellular
      matrix protein expression in the human placenta.
AB  - The extracellular matrix (ECM) protein fibronectin (FN) is a critical regulator
      of uterine-placental adherence. In the present report we compared the effects of
      glucocorticoids on FN expression in cytotrophoblast cultures isolated from human
      first trimester and term placentas to elucidate potential steroid-dependent
      cellular mechanisms associated with human parturition. Based on immunoassays,
      treatment of first trimester cytotrophoblasts with 10(-7) M dexamethasone (DEX)
      for 2 cr 4 days reduced medium levels of oncofetal FN (onfFN; i.e. FNs bearing an
      oncofetal epitope) to approximately 80% of control levels. Conversely, treatment
      of cytotrophoblasts isolated from term placentas with DEX dramatically reduced
      medium levels of onfFN to approximately 12% of control values. Treatment of both
      first trimester and term cells with 10(-6) M progestin, mineralocorticoid, or
      estrogen had no significant effect on onfFN expression in either cell type.
      Glucocorticoids specifically down-regulated medium levels of onfFN in term cells,
      but not in first trimester cells. In contrast, DEX treatment promoted an
      approximately 3- to 7-fold increase in levels of hCG in both first trimester and
      term cytotrophoblasts, suggesting that the effects of glucocorticoid on FN and
      hCG expression are elicited through independent cell-signaling pathways. In first
      trimester cells, DEX promoted a reduction in rates of FN and laminin synthesis to
      60-70% of control levels. In term cells, DEX treatment reduced levels of FN and
      laminin synthesis to approximately 10% of control levels. Similarly, DEX
      treatment down-regulated levels of FN mRNA to approximately 60% and 10% of
      control values in first trimester and term cells, respectively. The first
      trimester of human pregnancy is associated with low levels of glucocorticoids and
      reduced glucocorticoid responsiveness. These conditions would favor high levels
      of placental ECM protein synthesis, thus stabilizing uterine-placental adherence.
      Conversely, elevated levels of glucocorticoids near parturition and increased
      glucocorticoid responsiveness would inhibit placental ECM protein synthesis,
      reducing uterine-placental adherence and promoting the separation of placenta
      from uterus.

PMID- 8156907
TI  - Mechanisms of insulin resistance during acute endotoxemia.
AB  - We characterized the mechanisms underlying acute endotoxin-induced alterations in
      glucose metabolism and determined the extent to which catecholamines mediate
      these changes. Acute endotoxemia was induced in chronically catheterized awake
      rats by a bolus injection of lipopolysaccharide (LPS; 1 mg/kg; LD10). Basal
      glucose turnover (Rt; infusion of [5-3H]glucose), in vivo insulin action on
      overall glucose utilization (euglycemic clamp), glycolysis, and glycogen
      synthesis were determined in four groups of rats. These groups received 1) LPS
      (LPS rats; n = 6), 2) saline (control rats; n = 6), 3) LPS and alpha beta
      blockade (alpha beta-blockade and LPS rats; n = 9), or 4) saline and alpha beta
      blockade (alpha beta-blockade control rats; n = 9). In the basal state, LPS
      induced hypotension and transient hyperglycemia. These changes were associated
      with glycogen depletion in both skeletal muscle and liver, and increased Rt.
      During hyperinsulinemia, whole body glucose disposal was 37% decreased (105 vs.
      166 mumol/kg.min; P < 0.01). This whole body insulin resistance was characterized
      by decreased glycogen synthesis and glycogen synthase activity, but not by
      altered whole body glycolysis. alpha beta-Blockade abolished transient
      hyperglycemia, increased Rt, and accelerated basal liver glycogen depletion (45
      vs. 105 mmol/kg dry, LPS and alpha beta-blockade rats vs. LPS rats; P < 0.05),
      but inhibited muscle glycogenolysis. alpha beta-Blockade did not reverse the
      insulin resistance induced by endotoxin. These data suggest that catecholamines
      counteract the LPS-induced increase in basal glucose turnover and stimulate
      muscle glycogenolysis during acute endotoxemia. These effects might explain the
      better preservation of hepatic glycogen in the absence than in the presence of
      alpha beta-blockade and serve as a defense mechanism against hypoglycemia.
      Catecholamines do not seem to be the immediate causes of insulin resistance
      during acute endotoxemia.

PMID- 8156908
TI  - Expression and regulation of transforming growth factor-beta 1 messenger
      ribonucleic acid and protein in cultured porcine Leydig and Sertoli cells.
AB  - In the present work, the expression and secretion of transforming growth factor
      beta 1 (TGF beta 1) by immature pig Leydig and Sertoli cells were investigated.
      Both cell types express two TGF beta 1 mRNA transcripts of 2.5 and 3.5 kilobases,
      and the levels were 2.6-fold higher in Leydig than in Sertoli cells. In the
      latter cells, mRNA levels were enhanced when cultured cells were stimulated by
      epidermal growth factor and phorbol ester (4-beta-phorbol 12-myristate 13
      acetate) and significantly decreased by FSH and testosterone. Using a polyclonal
      antibody raised against a synthetic peptide that corresponded to the carboxyl
      terminal region of TGF beta 1 and recognized this peptide, but not TGF beta 2 or
      TGF beta 3, specific immunostaining of both Leydig and Sertoli cells was
      demonstrated in situ, after cell isolation, and during culture. The
      immunostaining was more marked in Leydig cells than in Sertoli cells. Western
      blot analysis of Leydig or Sertoli cell-conditioned medium demonstrated a band of
      25 kilodaltons, which was shifted to 12.5 kilodaltons under reducing conditions.
      Using the mink lung epithelial cell bioassay for TGF beta 1, we could demonstrate
      the presence of TGF beta 1-like activity in Leydig and Sertoli cell-conditioned
      media after acid treatment, but not before activation. The inhibitory effects of
      both pure TGF beta 1 and acidified conditioned medium were almost completely
      blunted by the TGF beta 1 antibody. The amounts of TGF beta 1 secreted by Sertoli
      and Leydig cells were not significantly different and varied between 400-800
      pg/48 h.10(6) cells. These studies demonstrate for the first time that both pig
      Leydig and Sertoli cells express TGF beta 1 mRNA, and the TGF beta 1-like
      activity secreted by these cells corresponds to TGF beta 1. As TGF beta 1 has
      been demonstrated to have strong effects on testicular cells, in particular on
      Leydig cell functions, it is suggested that local secreted TGF beta 1 may play a
      role in the autocrine/paracrine regulation of testicular functions.

PMID- 8156909
TI  - Amylin is an agonist of the renal porcine calcitonin receptor.
AB  - The cloned renal porcine calcitonin (pCT) receptor cDNA expressed by transient
      transfection in COS-1 cells or stable transfection in HEK-293 cells was assayed
      for interaction with CT, amylin, and CT gene-related peptide. Both [125I]salmon
      CT ([125I]sCT) and [125I]rat amylin displayed specific binding to transfected
      cells, and in both cases, pCT and rat amylin were equipotent in competing for
      binding. sCT was most potent in binding competition assays, whereas human CT and
      rat or human CT gene-related peptide did not compete. Despite the greater
      apparent affinity of sCT for receptor binding, sCT, pCT, and rat amylin had
      similar efficacies in stimulating the production of cAMP in the stably
      transfected cell line (EC50, 0.5-1.6 x 10(-9) M). These results contrasted with
      those obtained with the rat C1a CT receptor, for which amylin did not compete for
      [125I]sCT binding and stimulated cAMP production only at high concentrations.
      These results show that pCT and amylin interact with similar potencies with the
      pCT receptor and suggest that amylin may act as a natural ligand for this
      receptor.

PMID- 8156910
TI  - Prolactin receptor expression in human hematopoietic tissues analyzed by flow
      cytofluorometry.
AB  - PRL receptor (PRL-R) expression has been analyzed in human hematopoietic tissues
      using flow cytofluorometric analysis with a series of biotinylated monoclonal
      antibodies (mAbs) directed against the extracellular domain of the rat liver PRL
      R. In the thymus, more than 75% of cells were labeled by the anti-PRL-R mAb.
      Regarding PRL-R expression in the four T-cell subsets defined by CD4/CD8
      expression, the majority of cells expressed low receptor levels, whereas a
      minority of double negative (CD4-CD8-) and single positive CD4+ cells were
      strongly labeled by the anti-PRL-R mAb. In the peripheral blood, an average of
      80% of lymphoid cells, comprising all B-cells, all monocytes, and 75% of T-cells,
      were consistently PRL-R positive. Regarding T-cell subsets, similar percentages
      of PRL-R+ cells were observed in CD4+ and CD8+ peripheral lymphocytes (70-75%),
      and the density of labeling per cell was significantly lower than that occurring
      in B-cells or monocytes. Interestingly, the intensity of labeling significantly
      increased in peripheral T-cells after T-cell activation. The ubiquitous
      distribution of PRL-R in bone marrow stem cells, B-cells, monocytes, and T-cells
      was confirmed by the positive staining obtained in a set of human lymphoid cell
      lines. These data along with those showing that the PRL gene is specifically
      expressed in human T-cells suggest that lymphocyte PRL may act in a paracrine or
      autocrine fashion in both central and peripheral lymphoid organs.

PMID- 8156911
TI  - Role of the subfornical organ in the relaxin-induced prolongation of gestation in
      the rat.
AB  - The role of the subfornical organ in the timing of birth in the rat was
      investigated. Animals with radiofrequency lesions of the subfornical organ made
      on day 12 of pregnancy gave birth significantly earlier (P < 0.05) than intact
      and control-lesioned rats. Animals with lesions made on day 19 of pregnancy gave
      birth within control times. In addition, the natural fall in plasma relaxin
      observed at the end of gestation in rats was prevented by i.v. infusion of
      porcine relaxin (4.2 micrograms/h for 5 days from day 19 of gestation), which
      maintained plasma relaxin levels at approximately 100 ng/ml. This rate of
      infusion was selected because the resultant circulating levels of relaxin reflect
      plasma concentrations observed on day 20 of pregnancy in rats. The effect of
      lesion of the subfornical organ was then studied on the timing of birth in
      relaxin-infused rats. Intact animals and rats with control lesions receiving an
      infusion of relaxin had significantly (P < 0.05) prolonged pregnancies compared
      with intact saline-infused controls. However, the timing of birth of rats with
      lesions of the subfornical organ receiving an infusion of relaxin was not
      significantly (P > 0.05) different from that in intact saline-infused controls.
      The results support the hypothesis that the subfornical organ appears to mediate
      the central effects of relaxin and may have a natural role in the events that
      lead to delivery in the rat.

PMID- 8156912
TI  - Stearyl-norleucine-vasoactive intestinal peptide (VIP): a novel VIP analog for
      noninvasive impotence treatment.
AB  - The present report relates to pharmaceutical composition for the treatment of
      male impotence. The transdermal application of a potent derivative of vasoactive
      intestinal peptide (VIP) coupled to a suitable hydrophobic moiety (e.g. stearyl
      VIP) in a suitable ointment composition (e.g. Sefsol) enhances sexual activity
      and erection formation in a variety of impotence models in rats (sterile rats,
      diabetic rats, and animals with high blood pressure). Furthermore, exchange of
      the methionine in position 17 with norleucine enhances biological activity. Thus,
      stearyl-Nle17-VIP may be considered useful for the treatment of impotence.

PMID- 8156913
TI  - The effect on vertebral bone mass and strength of long term treatment with
      antiresorptive agents (estrogen and calcitonin), human parathyroid hormone-(1
      38), and combination therapy, assessed in aged ovariectomized rats.
AB  - The aim of the study was to assess the long term effect of the antiresorptive
      agents estrogen and salmon calcitonin, the anabolic drug PTH, and combination
      therapy on vertebral bone mass and bone biomechanical competence in aged
      osteopenic ovariectomized (OVX) rats. Seventy-nine 1-yr-old retired breeder
      Wistar rats were randomized into seven groups: 1) sham-operated, 2) OVX, 3) OVX
      plus estrogen, 4) OVX plus salmon calcitonin, 5) OVX plus human (h) PTH-(1-38),
      6) OVX plus hPTH-(1-38) and estrogen, and finally, 7) OVX plus hPTH-(1-38) and
      calcitonin. Treatment regimens were initiated 8 weeks after ovariectomy and
      continued for 24 weeks. Whole body bone mass was measured by dual photon
      absorptiometry at intervals of 4 weeks and at death. Changes in spinal bone mass
      (BMC), biomechanical competence, and structure were assessed from the lumbar
      vertebral bodies. The results revealed a protective effect of both estrogen and
      calcitonin on ovariectomy-induced loss of whole body bone mass, but only estrogen
      had a significant effect on spinal BMC. hPTH-(1-38) monotherapy increased
      vertebral bone mass (BMC and ash content), size, and biomechanical parameters 20
      80% over OVX levels. A more rapid effect on vertebral bone mass was seen when
      hPTH-(1-38) was combined with estrogen or salmon calcitonin. The study has shown
      that in aged OVX osteopenic rats, hPTH-(1-38) therapy increases vertebral bone
      mass and bone quality and also maintains trabecular connectivity. Both estrogen
      and calcitonin reduce the ovariectomy-induced bone loss, but cannot restore bone
      mass to sham-operated levels. On the basis of this study, it is concluded that
      PTH therapy seems to hold promise in the management of postmenopausal and age
      related osteoporosis.

PMID- 8156914
TI  - The sensitivity of hepatic CYP2C gene expression to baseline growth hormone (GH)
      bioactivity in dwarf rats: effects of GH-binding protein in vivo.
AB  - Hepatic mRNA transcripts for the steroid-metabolizing enzymes cytochrome P4502C11
      (male specific) and P4502C12 (female specific) differ in abundance by 10- to 20
      fold in male and female rats and are regulated by their different patterns of GH
      secretion. This sex difference is also found in dwarf rats with low GH secretion,
      implying that these transcripts may be very sensitive to low level GH exposure.
      This has now been characterized in normal and dwarf rats. Continuous i.v.
      infusion of recombinant human (h) GH (0, 3, 12, and 48 micrograms/day) in both
      dwarf and normal male rats caused a dose-dependent decrease in P4502C11 and an
      increase in P4502C12, so that the 2C11/2C12 ratio fell from 17.9 +/- 1.3 to 1.5
      +/- 1.0 in normal males and from 6.5 +/- 0.9 to 0.4 +/- 0.3 in dwarf males (0 vs.
      48 micrograms hGH/day); over this dose range of hGH, body weight gain, total
      hepatic insulin-like growth factor-I mRNA levels, and plasma GHBP levels were
      largely unaffected. These effects of hGH were pattern dependent. The 2C11/2C12
      ratio in dwarf males was feminized (from 11.9 +/- 1.3 to 0.08 +/- 0.03) by
      continuous infusion of hGH (36 micrograms/day), whereas a pulsatile infusion (3
      min pulses every 3 h) of the same daily hGH dose was much less effective. Neither
      continuous nor pulsatile hGH affected P4502C11 or P4502C12 transcripts in dwarf
      females, although pulsatile hGH infusion caused a significant weight gain. To
      test whether baseline GH levels could be modified by circulating GH-binding
      protein (GHBP), hGH infusions were given with and without recombinant hGHBP in
      different patterns. Pulsatile infusions of recombinant hGHBP (42 micrograms/day,
      i.v.) did not prevent the feminizing effect of continuously infused hGH (36
      micrograms/day, sc) in dwarf males (2C11/2C12 ratios were 0.08 +/- 0.01 and 0.09
      +/- 0.01 for hGH vs. hGH plus hGHBP, respectively). This suggested that
      intermittent complex formation with GHBP did not prevent continuous access of hGH
      to the hepatic GH receptors. Furthermore, pulses of hGH complexed with GHBP
      significantly reduced the 2C11/2C12 ratio in dwarf males (from 21.5 +/- 3.9 with
      pulsatile hGH alone to 9.2 +/- 2.5 with pulses of hGH plus hGHBP), indicating
      that GHBP prolongs the exposure to hGH. Thus, 2C11/2C12 expression is very
      sensitive to basal GH levels in dwarf rats, and GHBP can alter hepatic gene
      expression by modifying the pattern of GH exposure.

PMID- 8156915
TI  - Human chorionic gonadotropin decreases insulin-like growth factor-I gene
      transcription in rat Leydig cells.
AB  - Insulin-like growth factor-I (IGF-I) and hCG have synergistic effects on Leydig
      cell steroidogenesis in primary culture. In the present study, we investigated
      the effects of hCG on IGF-I gene transcription in Leydig cells. Purified Leydig
      cells (8-10 x 10(6) cells/100-mm dish) obtained from 50- to 65-day-old male
      Sprague-Dawley rats were cultured for 24 h. After medium change, hCG (0.1-10
      ng/ml) or 8-bromo-cAMP (0.1 mM) was added, and cultures were continued for
      varying periods of time. In response to stimulation with hCG, there was a marked
      increase in the expression of cholesterol side-chain cleavage cytochrome P450
      mRNA. In contrast, hCG caused time- and dose-dependent decrements in IGF-I mRNA
      levels. Both large [7.5-kilobase (kb)] and small (0.8- to 1.2-kb) species of IGF
      I mRNAs were markedly decreased 6 h after treatment with hCG. hCG in a
      concentration of 0.1 ng/ml did not alter IGF-I mRNA levels. Higher concentrations
      of hCG (1 and 10 ng/ml) markedly decreased both 7.5- and 0.8- to 1.2-kb IGF-I
      mRNAs (80% and 56% reductions, respectively). 8-Bromo-cAMP (0.1 mM) also markedly
      reduced IGF-I mRNA levels. Finally, we evaluated the effects of hCG on the
      stability and transcription rates of IGF-I mRNA. We found that t1/2 of IGF-I mRNA
      for control Leydig cells was 3.86 h, which was not significantly different from
      that of hCG-treated cells (t1/2 = 3.41 h). This indicates that treatment with hCG
      did not change the stability of IGF-I mRNA. The average transcription rate per h
      for IGF-I mRNA decreased from 1 (for control cells) to 0.74 (for hCG-treated
      cells). The t1/2 values and rates of transcription for beta-actin were 7.39 and
      7.16 h, and 1 and 0.94 for control and hCG-treated cells, respectively, showing
      that RNA stability and rates of transcription did not change significantly for
      the beta-actin transcript. In conclusion, we have unequivocally demonstrated that
      hCG decreases the expression and transcription of IGF-I mRNA in Leydig cells.

PMID- 8156916
TI  - Interleukin-6 secretion from rat Leydig cells in culture.
AB  - Recent evidence indicates that interleukin-6 (IL-6) acts on Sertoli cells to
      modulate secretory function. IL-6 is also detected in medium bathing tissue or
      cells from the seminiferous tubule, suggesting a testicular regulatory role.
      Because other cytokines found to be active in testicular function have more than
      one site of production, we examined whether Leydig cells may serve as an
      alternate source of IL-6. Purified Leydig cells were cultured with or without
      modulatory substances, and the medium was subjected to the 7TD1 bioassay for IL
      6. Northern analysis using an IL-6 cDNA probe was performed on companion cell
      preparations. Incubation with either hCG or IL-1 beta increased the levels of
      bioactive IL-6 released into the medium and IL-6 mRNA detected in the cells in a
      dose-related manner. When used together, these agents had an additive stimulatory
      influence on both the release of IL-6 bioactivity and the amount of IL-6 mRNA.
      Our results demonstrate that IL-6 is secreted from enriched preparations of
      Leydig cells and that its release is under the control of at least two modulators
      of testicular function. Identification of interstitial cells as a site of IL-6
      production coupled with reports of IL-6 release and action in seminiferous
      tubular cell preparations suggest that IL-6 may serve a role in signal
      integration or communication from one testicular location to another.

PMID- 8156917
TI  - Divergent tissue-specific and developmental expression of receptors for glucagon
      and glucagon-like peptide-1 in the mouse.
AB  - Proglucagon mRNA transcripts are transcribed in the pancreas, bowel, and brain,
      after which posttranslational processing results in the liberation of a different
      profile of biologically active peptides in each tissue. The receptors for two of
      these peptides, glucagon and glucagon-like peptide-1 (GLP-1), have recently been
      identified, but only limited information is available concerning the tissue- and
      age-specific distribution of these receptors in vivo. We have investigated the
      expression of these receptors in the mouse using a combination of Northern blot
      analysis and reverse transcription-polymerase chain reaction. DNA sequence
      analysis of a partial mouse glucagon receptor cDNA demonstrated a high degree of
      sequence conservation across rodent species. Glucagon receptor mRNA transcripts
      were detectable by Northern blotting in poly(A)+ RNA from liver and kidney.
      Reverse transcription-polymerase chain reaction also detected glucagon receptor
      mRNA transcripts in both fetal and adult pancreas and lung, jejunum, and ileum,
      but not in the large intestine. In contrast, mRNA transcripts for the GLP-1
      receptor were detected in both small and large intestine as well as in pancreas,
      liver, lung, and kidney. Both glucagon and GLP-1 receptor mRNA transcripts were
      identified in different regions of the fetal and adult mouse brain, but the
      relative levels of GLP-1 receptor mRNA transcripts were much greater in the
      central nervous system. Furthermore, regulation of the GLP-1 receptor (but not
      the glucagon receptor) gene in the brain resembled the pattern of region-specific
      gene expression recently defined for the mouse proglucagon gene. Taken together,
      these studies define novel sites for both glucagon and GLP-1 receptor gene
      expression in the mouse and suggest that different regulatory mechanisms have
      evolved for tissue-specific and developmental control of receptor gene
      expression.

PMID- 8156918
TI  - Sex difference in the action of activin-A on cell proliferation of
      differentiating rat gonad.
AB  - The effect of recombinant bovine activin-A on DNA synthesis in fetal rat gonads
      and mesonephroi was studied in vitro by using [3H]thymidine autoradiography to
      evaluate the role of activin in the regulation of gonadal development. mRNA
      levels of inhibin-beta A and -beta B, activin receptor II and IIB (ActRII and
      ActRIIB), and follistatin were studied by Northern hybridization in the fetal rat
      gonads and mesonephroi. Activin stimulated thymidine incorporation in ovaries and
      female mesonephroi on days 14 and 15 postcoitum (pc) in a dose-dependent manner,
      as assessed by autoradiography. In contrast, activin inhibited thymidine
      incorporation in testes and male mesonephroi on day 14 pc in a dose-dependent
      way. On day 18 pc, the stimulatory effect of activin in ovary was nearly lost,
      whereas that in mesonephros was still pronounced. Activin had no effect on
      thymidine incorporation in testes and male mesonephroi on day 15 or 18 pc.
      Inhibin-beta A mRNA was seen in testes and mesonephroi in the male and in
      mesonephroi in the female of 15 and 18 day pc embryos. Inhibin-beta A mRNA
      expression was also seen in the testes and epididymes of newborn male rats and in
      the ovaries of 11-day-old postnatal rats. Inhibin-beta B mRNA was present in both
      testes and ovaries from 15 day pc onward. ActRIIB mRNA was most abundant in the
      testes, ovaries, and mesonephroi of 15 day pc embryos. The expression of ActRIIB
      message diminished during aging. ActRII mRNA was ubiquitously expressed during
      development. Follistatin mRNA was seen in the ovaries from 15 day pc onward and
      in the oviducts at 11 days postnatally. The present novel findings of activin
      subunit and receptor mRNA expression and activin action on gonadal and
      mesonephric cell proliferation suggest an important, sexually dimorphic role for
      this substance in fetal gonadal differentiation.

PMID- 8156919
TI  - Inhibition of aldosterone synthesis in rat adrenal cells by nicotine and related
      constituents of tobacco smoke.
AB  - Previous work has shown that nicotine and related constituents of tobacco smoke
      inhibit selected P450 enzymes in the glucocorticoid and sex steroid synthetic
      pathways. Because aldosterone synthesis is also cytochrome P450 dependent, we
      hypothesized a similar inhibitory action on aldosterone production. In this study
      we examined the effects of nicotine, anabasine (a related alkaloid), and cotinine
      (the major metabolite of nicotine) on in vitro aldosterone synthesis. Freshly
      isolated rat adrenal cells were assayed for corticosterone and aldosterone
      production in the basal state and after stimulation with ACTH or angiotensin-II
      (ANG-II). The addition of nicotine, anabasine, and cotinine in concentrations up
      to 100 microM did not inhibit stimulated corticosterone production. However,
      there was a potent dose-dependent inhibitory action of all three tobacco
      compounds on aldosterone production. The relative inhibitory potency was:
      cotinine > anabasine > nicotine. When employed at a concentration of 100 microM,
      the three compounds inhibited ACTH-stimulated aldosterone synthesis by 75%, 44%,
      and 21%, respectively. ANG-II-stimulated aldosterone synthesis was inhibited by
      92%, 78%, and 62%, respectively. The plasma cotinine concentration range attained
      in tobacco smokers is between 1-10 microM. When tested with [3H]corticosterone
      and [3H]progesterone as exogenous substrates, 1-10 microM cotinine caused a
      significant dose-dependent inhibition of ACTH- and ANG-II-stimulated aldosterone
      synthesis. Cotinine substantially blocked the conversion of corticosterone to 18
      hydroxycorticosterone, implicating the 18-hydroxylase or corticosterone 18
      methyloxidase-I (CMO-I) step as the major site of inhibition. In summary, our
      results indicate that tobacco compounds cause direct and specific inhibition of
      aldosterone synthesis, primarily at the CMO-I step. This enzymatic blockade would
      be expected to result in activation of the renin-angiotensin system in vivo. We
      postulate that chronic stimulation of the renin-angiotensin system by this
      mechanism might contribute to the cardiovascular damage that occurs with long
      term tobacco use.

PMID- 8156920
TI  - Inactivation by plasma may be responsible for lack of efficacy of parathyroid
      hormone antagonists in hypercalcemia of malignancy.
AB  - PTH-related protein (PTHrP) has been shown to be a major factor responsible for
      hypercalcemia of malignancy. PTHrP acts via the PTH/PTHrP receptor, and
      therefore, PTH antagonists might be expected to reverse the hypercalcemia in
      malignancy. In the present studies, the PTH antagonists [Tyr34]bovine (b) PTH-(7
      34)NH2, [D-Trp12,Tyr34]-bPTH-(7-34)NH2, or PTHrP-(7-34)NH2, were administered to
      hypercalcemic athymic nude mice bearing a human squamous cell carcinoma of the
      lung in 60- to 500-fold molar excess of a dose of PTHrP-(1-34) known to produce
      hypercalcemia. The antagonists had no significant effect on serum calcium levels.
      In an adenylyl cyclase assay using the ROS 17/2.8 cells, a potent PTH antagonist,
      [Leu11,D-Trp12]PTHrP-(7-34)NH2 was rapidly inactivated in the presence of rat or
      human plasma. This inactivation by plasma was not blocked by common inhibitors of
      proteolysis (aprotinin, soybean trypsin inhibitor, and leupeptin). Preliminary
      studies demonstrated that inactivation of the PTHrP antagonist was caused by a
      plasma component with an apparent mol wt of 230,000 daltons. The knowledge of the
      structure of the PTH/PTHrP receptor combined with the identification of a hormone
      inactivating plasma factor should facilitate the design of PTH-antagonists that
      are effective in vivo.

PMID- 8156921
TI  - Gonadotropin-releasing hormone-immunoreactive cell numbers change in response to
      social interactions.
AB  - Puberty is characterized by either a steroid-dependent or independent increase in
      the production and secretion of neural GnRH. Several measures have been used to
      assess the pubertal activation of neurons that express GnRH. Some morphological
      changes in these cells occur at puberty, but no dramatic changes indicative of
      increases in the synthesis of GnRH have been noted. In the musk shrew, puberty is
      induced by mating. We hypothesize that because the first mating facilitates the
      display of female sexual behavior and subsequent ovulation, that mating may have
      direct and rapid effects on GnRH neurons. Significant changes in the number of
      GnRH-immunoreactive (GnRH-ir) neurons in the brains of prepubertal virgin females
      were note after contact with males. Different populations of GnRH-ir cells were
      affected by different types of interactions with males. Exposure to an adult male
      across a wire barrier for 48 h increased the number of GnRH-ir cells in olfactory
      related nuclei. Mating increased GnRH-ir cell numbers in olfactory and ventral
      forebrain regions. Ovulation reduced GnRH-ir cell numbers in several forebrain
      nuclei. These rapid and quantitative responses of GnRH-ir neurons to social cues
      allow direct examination of the neuroendocrine changes that occur at puberty.

PMID- 8156922
TI  - 5 alpha-reductase activity in developing urogenital tracts of fetal and neonatal
      male mice.
AB  - 5 alpha-Reductase activity in testes and urogenital tract tissues from male mice
      at 14.5 days gestation and 0 days of age (birth) was assessed by measurement of
      metabolites of testosterone released into the medium in a serum-free culture
      system. In male mice at 14.5 days gestation, the testis and the cranial portion
      of the urogenital ridge (UGR), which develops into the epididymis, had little 5
      alpha-reductase activity. The caudal portion of the UGR, which develops into the
      seminal vesicle (SV), and the cranial portion of the urogenital sinus (UGS) had
      12-fold higher activity than the cranial portion of the UGR. 5 alpha-Reductase
      activity in the middle portion of UGR was intermediate between that of its
      cranial and caudal portions. The highest levels of 5 alpha-reductase activity
      were detected in the caudal portion of UGS, even though this higher value was not
      significantly different from those in the caudal UGR or the cranial UGS. In 0-day
      old male mice, 5 alpha-reductase activity of testis remained low at a level
      similar to that observed at 14.5 days gestation. The epididymis also exhibited
      low 5 alpha-reductase activity in 0-day-old mice, even though this activity had
      increased 2.2-fold relative to that observed in the cranial UGR at 14.5 days
      gestation. 5 alpha-Reductase activity of the cranial portion of UGS (prostatic
      rudiment) was relatively high on day 0 and similar to that in the same region at
      14.5 days gestation. The SV and bulbourethral gland (BUG) on day 0 had high 5
      alpha-reductase activity, which had increased 1.4- and 1.3-fold, respectively,
      compared to their 14.5 day embryonic anlage, although the increase was not
      significant. Through examination of 5 alpha-reductase activity regionally in the
      developing urogenital tract, it is evident that the concept that testosterone is
      the active androgen during Wolffian development is overly simplified. The present
      study suggests the importance of spatial/regional factors in Wolffian duct
      development in regard to the role of dihydrotestosterone. 5 alpha-reductase
      activity in the caudal Wolffian duct (SV rudiment) equals or exceeds that in the
      developing prostate, and at birth, dihydrotestosterone production is virtually
      identical in the SV and prostate. This suggests that 5 alpha-reduced androgens
      play a prominent role in the development of SV.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8156923
TI  - Ontogeny of luteinizing hormone receptor gene expression in the rat testis.
AB  - The ontogeny of expression of the LH receptor (LHR) gene was studied in rat
      testis between day 12.5 of fetal life and adulthood. Specific hybridization of
      testicular mRNA with a LHR cRNA probe encoding the extracellular domain of the
      receptor was found from day 16.5 of fetal life onward in Northern hybridization.
      Transcripts of 6.8, 4.2, and 2.7 kilobases were present at all ages, and a 1.8
      kilobase species was present mainly in the adult testes. Hybridization was most
      intensive in day 21.5 fetuses, decreased after birth, and increased again by
      adulthood. The LHR mRNA was also analyzed by the reverse transcriptase-polymerase
      chain reaction technique, with primers multiplying either the full-length LHR
      mRNA or its extracellular domain. The specificity of the DNA species generated
      was verified by Southern hybridization using a nested 32P-labeled
      oligonucleotide. The results indicated that a truncated mRNA form, encoding the
      extracellular part of LHR, appears 1 day before the full-length LHR mRNA, i.e. on
      fetal days 14.5 and 15.5, respectively. This is in striking contrast to the rat
      fetal ovary, in which a difference of more than 10 days is found in the
      appearance of these two LHR mRNAs (17.5 days of fetal and 7 days of postnatal
      age, respectively). The appearance of the full-length LHR mRNA coincides in both
      sexes with the developmental onset of LHR binding observed in earlier studies. In
      situ hybridization using an antisense cRNA probe demonstrated that the LHR mRNA
      was confined to Leydig cells at all fetal and postnatal ages studied. In
      conclusion, there is good correlation in the developing rat testes between the
      onset of LHR gene expression and LHR binding, as observed in earlier studies. The
      findings in the fetal testis are at striking variance with those in the ovary,
      which starts expressing the extracellular domain of the LHR mRNA at roughly the
      same age as the testis. However, the appearance of full-length LHR mRNA and the
      functional receptor are delayed until day 7 postpartum.

PMID- 8156924
TI  - The diurnal rhythm in adrenocorticotropin responses to restraint in
      adrenalectomized rats is determined by caloric intake.
AB  - There is a diurnal rhythm in ACTH responses to stressors that peaks, in
      nocturnally feeding rats, at the time of lights on, in the morning (AM). To
      determine whether this rhythm is subordinate to the rhythm in food intake, we
      tested the effects of removing food during the night or the day on ACTH responses
      in the AM or evening (PM) to the stimulus of restraint in 5-day-adrenalectomized
      rats. An overnight fast reduced the ACTH response to restraint with tail blood
      sampling in the AM to the low magnitude observed in the PM in rats fed ad
      libitum; by contrast, a fast of equivalent duration imposed during the day had no
      effect on the ACTH response to the stressor in the PM. Short term fasts did not
      alter the normal AM-PM rhythm in basal ACTH levels. The fasts did, however,
      significantly decrease the pituitary ACTH concentration at both times of day,
      suggesting that lack of food had stimulated ACTH secretion during the preceding
      14 h. Providing calories by either gavage or manipulation of food presentation
      increased ACTH responses to restraint in fasted adrenalectomized rats in both the
      AM and PM. Although four of four experiments showed that provision of calories to
      fasted rats resulted in increased ACTH responses to the stimulus of restraint,
      none of the manipulations of caloric intake fully restored ACTH responses in
      fasted rats to the high amplitude observed in ad libitum fed rats in the AM. We
      conclude that 1) unlike the circadian rhythm in basal activity in the
      hypothalamic-pituitary-adrenalocortical (HPA) system, the diurnal rhythm in ACTH
      responsiveness to stimuli is tightly coupled to the endogenous rhythm in energy
      intake; and 2) caloric deprivation per se appears to activate the HPA system at
      some time during the 14- to 17-h fast, but does not produce the normal
      facilitation in the AM response to acute restraint that is induced by chronic or
      prior stimulation of the HPA axis.

PMID- 8156925
TI  - 1,25-dihydroxyvitamin D3 stimulates adipocyte differentiation in cultures of
      fetal rat calvaria cells: comparison with the effects of dexamethasone.
AB  - Progenitor cells for several mesenchymally derived cell types exist within
      freshly isolated fetal rat calvaria (RC) cell populations. We have characterized
      the effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on the differentiation of
      adipocytes from primary RC cells and compared these effects with those of
      dexamethasone (Dex). RC cells were plated at 3 x 10(4)/35-mm dish, and cultures
      were maintained for 14-19 days in alpha-Minimum Essential Medium containing 10%
      fetal bovine serum, 50 micrograms/ml ascorbic acid, 10 mM Na beta
      glycerophosphate, and 0.1-100 nM 1,25-(OH)2D3 or 1-1000 nM Dex. Morphological
      (quantitation of adipocyte foci number and area after staining cultures with
      Sudan IV) and biochemical (glycerol-3-phosphate dehydrogenase activity) methods
      of assessing adipogenesis were used. In the presence of 1,25-(OH)2D3, adipocyte
      foci developed about 3 days after confluency as clusters of rounded or stellate
      cells. Stimulation of adipocyte foci development was dose dependent from 0.1-100
      nM and was maximal with 10 nM 1,25-(OH)2D3; half-maximal stimulation occurred at
      about 1 nM. The presence of ascorbic acid and beta-glycerophosphate was not
      required for 1,25-(OH)2D3-induced stimulation of adipocytes, but both
      significantly increased the number of adipocyte foci in the presence of 1,25
      (OH)2D3. The critical period for initiation of adipocyte differentiation with
      1,25-(OH)2D3 was between 1-9 days, and once committed along the adipogenic
      pathway, adipocytes maintained their differentiated state in the absence of 1,25
      (OH)2D3. Short term (48-h) pulses of 1,25-(OH)2D3 resulted in slight, but
      significant, increases in adipocyte formation. Other vitamin D3 metabolites were
      less effective than 1,25-(OH)2D3 in stimulating adipocyte differentiation. Dex (1
      100 nM) also caused a dose-dependent increase in the differentiation of adipocyte
      foci in RC cell cultures. The adipocyte foci that developed in the presence of
      Dex frequently appeared earlier in culture, i.e. when cells reached confluency on
      days 6-7, and were more diffuse than those forming with 1,25-(OH)2D3. The
      stimulation of adipocyte differentiation by 1,25-(OH)2D3, however, was greater
      than that by Dex in mixed RC II-V cells. The combined effects of 1,25-(OH)2D3 and
      Dex were additive at low concentrations and synergistic at higher concentrations
      of either 1,25-(OH)2D3 or Dex. The data show that bone cell populations isolated
      from fetal RC contain adipocyte progenitors and that 1,25-(OH)2D3 as well as Dex
      are potent regulators of adipocyte differentiation within these bone cell
      populations.

PMID- 8156926
TI  - Mechanical stimuli induce vascular parathyroid hormone-related protein gene
      expression in vivo and in vitro.
AB  - PTH-related peptide (PTHrP), the factor mediating the syndrome of humoral
      hypercalcemia of malignancy, is also expressed in smooth muscle cells (SMC) of
      the urinary bladder and uterus in response to mechanical distention and fetal
      occupancy, respectively. Vascular SMC also produce PTHrP, and its expression is
      induced by serum and vasoconstrictors, such as angiotensin-II. To determine
      whether mechanical distension affected vascular PTHrP gene expression, the
      abdominal aorta of adult male rats was balloon-distended, and aortae were
      collected at various times after the intervention. PTHrP mRNA was determined by
      competitive reverse transcriptase-polymerase chain reaction, using sequential
      dilutions of a cloned internally truncated PTHrP RNA fragment as standard. The
      molar concentration of PTHrP mRNA was obtained by extrapolating at a
      standard/wild-type band intensity ratio of 1:1. Aortic PTHrP mRNA was induced
      from a basal level of 19, to 22, 46, 36, 13, 12, 22, and 20 attamoles/mg total
      RNA 1, 2, 12, 24, and 48 h and 7 and 48 days after balloon distension,
      respectively. To determine whether mechanical events directly regulate vascular
      PTHrP gene expression, primary rat aortic SMC were plated and placed on a rocking
      device at 20 oscillations/min to create a gentle flowing motion of the culture
      medium. Rocking induced PTHrP mRNA of SMC exposed to either serum-free medium or
      10% serum by 2.5-and 4.0-fold at 4 h, and 2.9- and 3.7-fold at 24 h,
      respectively. These effects were oscillation rate dependent, potentiated by
      angiotensin-II, and specific, as similar changes were not observed in alpha-actin
      mRNA content. Flow motion-induced PTHrP mRNA at 24 h was partially decreased by
      10(-6) M colchicine (which inhibits microtubule assembly), but not by
      cytochalasin-E (which disrupts actin polymerization). As PTHrP is a known
      vasorelaxant, we propose that mechanical events induce the release of PTHrP by
      SMC, possibly to serve as a compliance factor or an agent for vascular
      remodeling.

PMID- 8156927
TI  - Synergistic induction of gene 33 expression by retinoic acid and insulin.
AB  - The expression of gene 33 in rat liver and hepatoma cells is regulated by
      multiple hormones and other bioactive agents. Previous studies have demonstrated
      a 15-fold increase in gene 33 mRNA after 1 h of insulin treatment. We demonstrate
      in this report that retinoic acid (RA) also controls the expression of this gene.
      Gene 33 mRNA levels are rapidly elevated by RA, with maximal accumulation (19
      fold over control) attained after just 1 h of RA treatment. The transcription
      rate of gene 33 was increased by RA to a maximum level 6-fold greater than
      control values. Studies with inhibitors of RNA synthesis demonstrated no increase
      in the stability of gene 33 mRNA in response to RA or insulin. In addition, a
      synergistic induction of both gene 33 mRNA levels and the transcription rate of
      gene 33 was observed when both RA and insulin were added together. In the
      presence of both hormones, the transcription rate was induced almost 20-fold in
      30 min, followed by a 49-fold increase in mRNA levels after 1 h. Thus, gene 33
      represents the first example of a gene whose transcription rate is elevated
      directly by both insulin and RA, and synergistically elevated by treatment with
      both hormones together.

PMID- 8156928
TI  - Calcium/calmodulin-dependent protein kinase-II activation in rat pituitary cells
      in the presence of thyrotropin-releasing hormone and dopamine.
AB  - PRL release from rat lactotrophs in response to TRH is Ca2+ dependent. TRH
      induced PRL release is inhibited either after repeated pulses of TRH or in the
      presence of dopamine. TRH, however, generates increases in intracellular Ca2+
      concentrations ([Ca2+]i) in both conditions. Calcium/calmodulin-dependent protein
      kinase-II (CaM kinase-II) is a ubiquitous enzyme implicated in secretion. To
      determine whether down-regulation of CaM kinase-II activity caused the lack of
      responsiveness to increases in [Ca2+]i, we measured the generation of
      calcium/calmodulin-independent kinase activity. Anterior pituitary cells contain
      a 50-kilodalton form of CaM kinase-II, determined by immunoblot, and the enzyme
      is in lactotrophs, determined by immunocytochemistry. TRH rapidly and transiently
      increased calcium/calmodulin-independent kinase activity; the increase was
      maximal by 15 sec and returned to basal by 2 min. When TRH pulses (1 microM, 15
      sec) were applied every 10 min, each pulse caused an increase in
      calcium/calmodulin-independent kinase activity of similar magnitude, and the
      activity returned to basal values between pulses. Pretreatment of cells with
      dopamine (1 microM; 30 min) inhibited PRL release, but did not prevent the
      increase in calcium/calmodulin-independent kinase activity. These results
      indicate that TRH still activates CaM kinase-II when PRL release is inhibited.
      Dopamine and repeated pulses of TRH must inhibit PRL release at a site after the
      TRH-induced increase in [Ca2+]i and at a site other than CaM kinase-II.

PMID- 8156929
TI  - Insulin-like growth factor-I and insulin have no differential effects on glucose
      production and utilization under conditions of hyperglycemia.
AB  - We have previously shown that in moderately hyperglycemic depancreatized dogs, a
      glucose-lowering infusion of insulin-like growth factor-I (IGF-I) increased
      glucose utilization and lactate more, and suppressed glucose production and
      lipolysis less, than an equipotent glucose-lowering dose of insulin. Similar
      differences have been observed by others in nondiabetic and diabetic rats. To
      determine whether the decline in glycemia was important in detecting differential
      effects of IGF-I and insulin on glucose turnover, IGF-I (0.43 micrograms/kg.min;
      n = 6) or insulin (0.9 mU/kg.min; n = 9) were infused for 180 min, while
      hyperglycemia (approximately 180 mg/dl) was maintained. The decline of plasma
      glucose specific activity was minimized by using the matched step tracer infusion
      ([6-3H]- and [2-3H]glucose) method. Our results confirmed the approximately 10%
      potency of IGF-I on glucose metabolism compared to insulin and the lack of effect
      of IGF-I on insulin clearance. Under conditions of hyperglycemia, the glucose
      turnover findings were unexpected; there was no difference in the inhibition of
      glucose production (difference from basal, 2.7 +/- 0.4 mg/kg.min with IGF-I and
      2.4 +/- 0.2 with insulin) or the stimulation of glucose utilization (difference
      from basal, 4.5 +/- 0.8 mg/kg.min with IGF-I and 4.7 +/- 1.3 with insulin).
      However, lactate increased more (P < 0.01) with IGF-I (from 1230 +/- 163 to a
      peak of 1903 +/- 349 microM) than insulin (from 1209 +/- 291 to 1535 +/- 340
      microM) despite the same increment in glucose utilization. FFA and glycerol
      declined more with insulin, but the difference was not significant. IGF-I and
      insulin suppressed plasma amino acids to an equivalent extent. We concluded that
      1) the differential effects of IGF-I and insulin on glucose turnover are masked
      under conditions of hyperglycemia; and 2) because insulin and IGF-I induced the
      same increment in glucose utilization, but lactate increased more with IGF-I, IGF
      I might affect intracellular glucose metabolism differently from insulin. The
      failure of IGF-I to induce greater glucose utilization than insulin during
      hyperglycemia, the greater rise in lactate with IGF-I treatment, and the absence
      of differential effects on proteolysis indicate that IGF-I might have only
      limited clinical application in the treatment of diabetes.

PMID- 8156930
TI  - Studies on the in vitro cytotoxic effect of amiodarone.
AB  - Amiodarone, a potent antiarrhythmic drug, contains 37.2% iodine by weight and may
      induce either hypo- or hyperthyroidism. The high iodine content of amiodarone may
      be responsible for both complications, but a cytotoxic effect of the drug on the
      thyroid resulting in thyroiditis has been reported. In the present study the
      cytotoxic effect of amiodarone was evaluated in three culture systems with
      different biological properties: 1) a strain of rat thyroid cells (FRTL-5 cells)
      that maintains most differentiated functions of normal thyroid cells, including
      an active iodide pump, but an inability to organify iodide; 2) a line of Chinese
      hamster ovary (CHO) fibroblasts; and 3) freshly prepared primary cultures of
      human thyroid follicles (hTF) that trap and organify iodide. Cells were
      radiolabeled with 51Cr and incubated for 24 h with medium alone, medium plus
      amiodarone (3.75-200 microM), medium plus an iodinated radiographic contrast
      agent (sodium diatrizoate; 7.5-200 microM), or medium plus potassium iodide (7.5
      300 microM). At concentrations ranging from 75-200 microM, amiodarone induced a
      significant and dose-dependent release of 51Cr in FRTL-5 cells. In contrast,
      diatrizoate or KI had no cytotoxic effect on FRTL-5 cells. In the same molar
      concentrations, amiodarone was also cytotoxic in CHO cells. In hTF, the release
      of 51Cr produced by amiodarone occurred at a lower concentration (37.5 vs. 75
      microM) and was significantly greater than that in FRTL-5 cells. The cytotoxic
      effect of amiodarone in hTF was partially, but significantly, reduced by
      methimazole, an inhibitor of iodide organification. In the FRTL-5 cell culture
      system, amiodarone also produced a dramatic inhibition of TSH-stimulated cell
      growth. This growth-inhibiting effect of amiodarone was evident at low
      concentrations (3.75-7.5 mumol/liter) of the drug, which did not produce
      significant cytotoxicity. In conclusion, 1) amiodarone had a cytotoxic effect in
      CHO fibroblasts, a nonthyroid cell line; 2) this cytotoxic effect occurred in
      thyroid cells independent of their ability to organify iodide; 3) however, the
      toxic effect of amiodarone was greater and occurred at a lower molar
      concentration in freshly prepared human thyroid follicles that trap and organify
      iodide; and 4) in the latter culture system, methimazole, an inhibitor of iodide
      organification, partially, but significantly, reduced the cytotoxic effect of
      amiodarone. These data suggest that thyroid cytotoxicity produced by amiodarone
      is mainly due to a direct effect of the drug on thyroid cells, but excess iodide
      released from the drug may contribute to its toxic action.

PMID- 8156931
TI  - The effects of raloxifene on tibia histomorphometry in ovariectomized rats.
AB  - Tissue-specific estrogen agonists may be useful in protecting against
      osteoporosis and the increased risk of coronary heart disease in postmenopausal
      women with minimal undesired effects on reproductive tissues. The actions of the
      mixed estrogen agonist/antagonist raloxifene on selected estrogen target tissues
      were determined in ovariectomized (OVX) rats immediately postovariectomy. Five
      groups of 75-day-old Sprague-Dawley rats were studied; baseline controls, sham
      operated controls, OVX controls, OVX animals treated with estrogen (0.1 mg 17
      alpha-ethynyl estradiol/kg.day), and OVX animals treated with raloxifene (3
      mg/kg.day). Fluorochrome labels were given on days 1, 28, and 34. The baseline
      controls were killed on day 2, and the remaining groups on day 35. Ovariectomy
      increased tibial longitudinal growth rate as well as measurements related to
      radial growth and cancellous bone turnover. Ovariectomy decreased cancellous bone
      area and uterine weight, and increased serum cholesterol, bone elongation, and
      radial bone growth. Estrogen treatment prevented these changes in OVX rats.
      Raloxifene prevented cancellous osteopenia as well as the changes in radial bone
      growth, bone resorption, and blood cholesterol, but was less effective in
      reducing cancellous bone formation and did not prevent uterine atrophy. These
      findings suggest that raloxifene is a target-specific, mixed estrogen
      agonist/antagonist. At the concentration studied, raloxifene had potent
      estrogenic activity on bone resorption and serum cholesterol, a lesser effect on
      bone formation, and minimal activity on uterine wet weight.

PMID- 8156932
TI  - Fibroblast growth factor in the hypothalamic-pituitary axis: differential
      expression of fibroblast growth factor-2 and a high affinity receptor.
AB  - In situ hybridization and immunohistochemistry were used to map gene expression
      and protein distribution of basic fibroblast growth factor (FGF-2) in the
      hypothalamic-pituitary system. Although the expression of FGF-2 mRNA in the
      pituitary is low, the protein is widely distributed in both its neural and
      anterior lobes. In the anterior lobe, immunoreactive (ir-) FGF-2 localizes to
      basement membranes and select endocrine cells. In the neural lobe, ir-FGF-2 is
      detected in basement membranes, pituicytes, and Herring bodies. Analyses of FGF
      high affinity receptor (FGFR) immunoreactivity in the anterior pituitary
      establishes a distribution of FGFR similar to that of FGF-2. In the neural lobe,
      ir-FGFR is associated with nerve fibers, pituicytes, and Herring bodies. Unlike
      FGF-2, the distribution of FGFR1 mRNA correlates well with the presence of the
      immunoreactive receptor. In the hypothalamus, magnocellular neurons of
      paraventricular and supraoptic nuclei contain ir-FGF-2 and ir-FGFR. In the median
      eminence, ir-FGF-2 and ir-FGFR is associated with fibers, glial, and endothelial
      cells. Ependymal and subependymal cells lining the third ventricle also show high
      levels of ir-FGF-2 and ir-FGFR and mRNAs. Overall, there is a specific and
      selective distribution of FGF-2 and its high affinity receptor(s) in the
      hypothalamo-pituitary axis. This localization lead us to postulate a role in
      neurohypophyseal functions, possibly water balance.

PMID- 8156933
TI  - Immunocytochemical localization of 4-ene steroid 5 alpha-reductase type 1 along
      the rat epididymis during postnatal development.
AB  - Dihydrotestosterone (DHT), the active androgen in many tissues, is synthesized
      from testosterone by the enzyme 4-ene steroid 5 alpha-reductase (5 alpha
      reductase; EC 1.3.1.22). In the epididymis, the maturation and storage of
      spermatozoa are dependent on the presence of 5 alpha-reduced androgens. The
      regulation of epididymal 5 alpha-reductase is complex. To date, the regulation of
      this enzyme has been studied extensively at the level of enzymatic activity and
      more recently at the mRNA level. Regulation at the level of the protein, however,
      remains poorly understood. We have raised rabbit polyclonal antibodies to a 24
      mer synthetic peptide whose sequence was determined from the predicted amino acid
      sequence for rat 5 alpha-reductase type 1 to immunolocalize the 5 alpha-reductase
      type 1 protein in the rat epididymis during postnatal development. Western blot
      analysis revealed a specific immunoreactive band of 26 kilodaltons in male rat
      liver, epididymis, and prostate; this apparent molecular size is identical to
      that obtained when the 5 alpha-reductase type 1 cDNA is expressed in mammalian
      cells. Furthermore, the relative protein levels, liver > epididymis > prostate,
      were consistent with the mRNA levels for type 1 rat 5 alpha-reductase. Perfusion
      fixed paraffin-embedded epididymal tissue sections were used to immunolocalize
      type 1 5 alpha-reductase. In the adult rat epididymis, the most intense
      immunoperoxidase reaction was observed in a discrete lobule of the initial
      segment of the epididymis. A progressive decrease in staining intensity occurred
      distally along the tissue to the cauda epididymis. The staining reaction was
      specific to cytoplasmic elements of epithelial principal cells; no reaction was
      evident over nuclei. However, specifically in the initial segment, very intense
      staining was seen in the infranuclear region of the principal cells. In the
      proximal caput epididymidis, the staining was primarily confined to an oval
      region above the nuclei, whereas in the remaining epididymal regions, weak
      staining was seen throughout the cytoplasm. Thus, the intracellular localization
      of the 5 alpha-reductase type 1 protein changed as one moved down the epididymis.
      Finally, the pattern of immunolocalization of 5 alpha-reductase type 1 protein
      was different in the epididymis of rats of different postnatal ages. On day 7, no
      reactivity was noted; by day 28, a weak apical staining of principal cells was
      seen throughout the epididymis; by day 47, the adult pattern of staining had been
      established. Our results revealed that the expression and intracellular
      localization of the 5 alpha-reductase type 1 protein are both age dependent and
      epididymal segment specific.

PMID- 8156934
TI  - Androgen receptor distribution in rat testis: new implications for androgen
      regulation of spermatogenesis.
AB  - The distribution of the androgen receptor (AR) in the adult rat testis was
      determined by biotin-streptavidin immunoperoxidase, employing tissue embedded in
      polyester wax which preserves antigenicity without compromising tissue
      preservation. The antibody probe used, which has been characterized previously,
      was an affinity purified, rabbit polyclonal antibody raised to the amino terminus
      peptide of the rat AR. Within the interstitial compartment, AR immunostaining was
      detected in some Leydig cells and all smooth muscle cells forming the walls of
      blood vessels, but endothelial cells of blood vessels were negative. Furthermore,
      in those Leydig cells that were clearly identified as exhibiting AR
      immunostaining, the intensity of the reaction varied. In the seminiferous tubules
      AR immunostaining was observed in all peritubular myoid cell nuclei, but not in
      the distal layer of lymphatic endothelial cells. In Sertoli cells, nuclear AR
      immunostaining was stage specific. Moderate AR immunostaining first became
      evident at late stage IV or early stage V of the cycle, reached a robust peak at
      stages VII-VIII, and then disappeared completely. Specific AR immunostaining was
      also discerned in the nuclei of stage XI elongated spermatids, the spermatids in
      which nuclear elongation is apparent but chromatin condensation has not yet
      begun. Next, with onset of chromatin condensation, nuclear AR immunostaining in
      elongated spermatids was not discerned concomitant with its detection in the
      cytoplasm of the germ cells. These results are interpreted in the following
      manner: 1) The presence of AR in Leydig cells is consistent with the hypothesis
      that androgens modify Leydig cell activity in an autocrine fashion. Further, that
      not all Leydig cells exhibited AR immunostaining at steady state suggests a
      differential, functional activity of these cells within the population. 2) The
      intense AR immunostaining of smooth muscle cells present in the interstitium
      indicates that these cells are targets for androgens. 3) AR immunoreactivity in
      both Sertoli and peritubular myoid cells suggests their involvement in the
      androgenic control of spermatogenesis. The stage specific AR immunoreactivity in
      Sertoli cells, however, may be more indicative of a specific androgen response
      during these stages, whereas peritubular cells may participate in the tonal
      maintenance of spermatogenesis. 4) The specific presence of AR in step 11
      elongated spermatids may suggest that androgens can act directly on germ cells to
      regulate spermatogenesis.

PMID- 8156935
TI  - Basement membrane regulation of Sertoli cells.

PMID- 8156936
TI  - Mammalian spermatogenesis in vivo and in vitro: a partnership of spermatogenic
      and somatic cell lineages.

PMID- 8156937
TI  - Transforming growth factor-beta gene family members and bone.

PMID- 8156938
TI  - Parathyroid hormone-related protein as a prohormone: posttranslational processing
      and receptor interactions.
AB  - Since the elucidation of the structures of the three human PRHrP isoforms in
      1987, information has rapidly accured which indicates that the role of PTHrP in
      normal physiology will prove to be crucial as well as exceedingly complex. The
      importance of the role of PTHrP in normal physiology is underscored by its broad
      tissue expression, by its intense evolutionary conservation, by its extremely
      early expression after fertilization of the ovum, and by the lethal consequences
      of PTHrP gene disruption. The complexity of the role of PTHrP in normal
      physiology increases almost monthly. This complexity is reflected in the broad
      tissue distribution of the peptide, its complex transcriptional regulation and
      mRNA instability motifs, and its multiple transcripts and isoforms. It is now
      clear that additional complexity exists at the level of posttranslational
      processing. Expression of the PTHrP gene leads to the tissue-specific processing
      and secretion of an increasingly complex family of derivative peptides, each with
      its own repertoire of cognate receptors, signal transduction pathways, and
      physiological consequences. Further elucidation of the posttranslational
      processing pathways and mechanisms can be anticipated in the coming years,
      coupled with a corresponding elucidation of multiple PTHrP receptors, their
      specific signal transduction pathways, and their unique physiological roles. The
      role of PTHrP in causing HHM is now clearly established. Work in the coming
      decade will focus on the normal physiological roles played by PTHrP.

PMID- 8156939
TI  - Human relaxins: chemistry and biology.

PMID- 8156940
TI  - Retinoic acid receptors and cellular retinoid binding proteins: complex interplay
      in retinoid signaling.

PMID- 8156941
TI  - Nutritional regulation of the insulin-like growth factors.
AB  - Nutrition is one of the main regulators of circulating IGF-I. In humans, serum
      IGF-I concentrations are markedly lowered by energy and/or protein deprivation.
      Both energy and proteins are critical in the regulation of serum IGF-I
      concentrations. Indeed, after fasting, optimal intake of both energy and protein
      is necessary for the rapid restoration of circulating IGF-I. We believe, however,
      that in adult humans energy may be somewhat more important than protein in this
      regard. While the lowest protein intake is able to increase IGF-I in the presence
      of adequate energy, there is a threshold energy requirement below which optimal
      protein intake fails to raise IGF-I after fasting. When energy intake is severely
      reduced, the carbohydrate content of the diet is a major determinant of
      responsiveness of IGF-I to GH. The essential amino acid content of the diet is
      also critical for the optimal restoration of IGF-I after fasting, when protein
      intake is reduced. The exquisite sensitivity of circulating IGF-I to nutrients,
      the nycthemeral stability of its concentrations and its relative short half-life
      constitute the basis for its use as a marker of both nutritional status and
      adequacy of nutritional rehabilitation. For these indications, IGF-I measurement
      is more sensitive and more specific than measurement of the other nutrient
      related serum proteins (albumin, prealbumin, transferrin, retinol-binding
      protein). Animal models have been developed to investigate the mechanisms
      responsible for the nutritional regulation of IGF-I. There is no doubt that many
      mechanisms are involved (Fig. 12). Decline of serum IGF-I in dietary restriction
      is independent of the diet-induced alterations in pituitary GH secretion. The
      role of the liver GH receptors is dependent on the severity of the nutritional
      insult. In severe dietary restriction (fasting), a marked decrease of the number
      of somatogenic receptors supports the role of a receptor defect in the decline of
      circulating IGF-I. In contrast, in less severe forms of dietary restriction
      (protein restriction), the decline of IGF-I results from a postreceptor defect in
      the GH action at the hepatic level. Nutritional deprivation decreases hepatic IGF
      I production by diminishing IGF-I gene expression. Decline in IGF-I gene
      expression is mainly caused by nutrient deficiency and less importantly by the
      nutritionally induced hormonal changes (insulin and T3). Diet restriction also
      increases the clearance and degradation of serum IGF-I through changes in the
      levels of circulating IGFBPs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8156942
TI  - Kynurenine pathway metabolites in cerebrospinal fluid and serum in complex
      partial seizures.
AB  - The kynurenine pathway metabolites, quinolinic acid (QUIN) and L-kynurenine are
      convulsants, whereas kynurenic acid (KYNA) is an antagonist of excitatory amino
      acid receptors. Imbalances in the concentrations of these metabolites have been
      implicated in the etiology of human seizure disorders. In the present study, L
      kynurenine and QUIN concentrations in both cerebrospinal fluid (CSF) and serum
      were reduced in patients with intractable complex partial seizures (CPS) in both
      the postictal period (15-75 min after a seizure) and the interictal period
      (absence of seizure for > 24 h) as compared with neurologically normal control
      subjects. Linear regression analyses and analysis of covariance showed that the
      reductions in serum QUIN and L-kynurenine were correlated to blood antiepileptic
      medication. L-Tryptophan (L-TRP) levels also tended to be lower in both CSF and
      serum of the seizure patients. CSF KYNA and serum 3-hydroxykynurenine
      concentrations were not affected in seizure patients, whereas serum levels of
      KYNA were reduced. 3-Hydroxykynurenine was not detected in the CSF of either
      control or seizure patients. The results do not support a role for a generalized
      reduction in KYNA concentrations or an increased ratio of QUIN:KYNA, or increases
      in CSF L-kynurenine in initiation and maintenance of intractable CPS humans.

PMID- 8156943
TI  - Mirror focus: function of seizure frequency and influence on outcome after
      surgery.
AB  - The concept of the mirror focus (MF) implies that an actively discharging
      epileptiform region may induce similar paroxysmal behavior in a homologous site.
      In a group of patients with complex partial seizures (CPS) we investigated
      whether occurrence of a MF was influenced by certain clinical factors and whether
      surgical outcome was influenced by the presence of an MF. Factors studied
      included age at onset, duration, and total number of seizures. Patients had had
      CPS for > 3 years and had pathologically proven temporal lobe neoplasms. Seizure
      frequency was estimated by the history-taking physician. We estimated total
      seizure number by multiplying frequency by duration. Seven patients had MF, and
      15 did not. Mean age at onset of seizures, duration of seizure disorder, and
      total seizure number did not vary statistically between the two groups of
      patients. All patients with an MF except 1 were seizure-free at follow-up. Ten of
      the 15 patients without MF were seizure-free. Three patients who were not seizure
      free had had subtotal resection owing to tumor overlap with eloquent cortex. We
      conclude that an MF is not a contraindication to operation even when the
      preponderance of interictal spike activity is contralateral to the tumor or when
      seizures appear to arise from the MF on scalp EEG.

PMID- 8156944
TI  - Electrophysiology of bimanual-bipedal automatisms.
AB  - To determine the localizing value and electrophysiology of bimanual-bipedal
      automatisms (BBAs), we studied these behaviors in 54 seizures of 8 patients with
      temporal or frontal lobe seizure onset. BBAs occurred with a frequency of 27% in
      frontal lobe epilepsy (FLE) and of 7% in temporal lobe epilepsy (TLE). The
      distribution of electrode sites showing ictal activity during these automatisms
      was significantly different in the two patient groups (0.0001 Chi-square). Mesio-
      and/or laterotemporal plus orbital frontal areas were involved areas when the
      behaviors appeared in patients with TLE; dorsolateral and mesiofrontal regions
      were the most commonly involved when the behaviors occurred during the course of
      frontal lobe seizures. We concluded that BBAs represent activation of frontal
      lobe circuitry but are not unique to seizures of frontal lobe origin. Eyelid
      flutter and repetitive body movements in either the axial or sagittal plane were
      significantly associated with the frontal lobe group whereas oral-alimentary
      automatisms were associated with the temporal lobe group. Thus, these associated
      behaviors may help indicate whether a frontal or temporal lobe seizure onset has
      occurred when BBAs are observed. A new concept of ictal expression is proposed to
      conform with the results as well as with other apparently disparate ictal
      behaviors that may have localizing value.

PMID- 8156945
TI  - Magnetoencephalographic evaluation of children and adolescents with intractable
      epilepsy.
AB  - Magnetoencephalographic (MEG) discharges were recorded with multichannel
      superconducting quantum interference device (SQUID) gradiometers in 13 young
      candidates for epilepsy surgery. The sources of epileptic activity were related
      to generators of somatosensory and auditory evoked cortical responses and
      projected on magnetic resonance imaging (MRI) scans. Seven subjects had
      restricted or regional MEG foci, located in the frontoopercular (1), sensorimotor
      (3), perisylvian (1), mesiotemporal (1), or temporooccipital cortex (1). The MEG
      foci in the 3 patients who underwent operation agreed with the intracranial
      findings. Findings in the other patients emphasize the need to collect further
      data to define the ultimate role of MEG in preoperative evaluation of epilepsy.

PMID- 8156946
TI  - Juvenile myoclonic epilepsy: a 5-year prospective study.
AB  - We made a long term prospective study of 66 patients with juvenile myoclonic
      epilepsy (JME). Prevalence was 10.2% among 672 patients with epilepsies. Sex
      distribution was equal. Sixty-three were not diagnosed on referral; JME was not
      initially recognized in the epilepsy clinic in 22. Clinical typical absence
      seizures were reported in 33.3%, myoclonic jerks in 97% and generalized tonic
      clonic seizures (GTC) in 78.8% of the patients. Mean age (+/- SD) at onset was
      10.5 +/- 3.4 years (range 5-16 years) for absence seizures, 15 +/- 3.5 years
      (range 8-26 years) for myoclonic jerks, and 16 +/- 3.5 years (9-28) years (range
      1-9 years) and GTC by 4.4 +/- 2.7 years (range 1-8 years) in 14 (21.2%) patients
      who manifested all three types of seizure. Absence were never antedated by
      myoclonic jerks or GTC. Myoclonic jerks occurred on awakening in 87.5% of the
      patients. GTC occurred mainly on awakening, but other patients had nocturnal or
      diurnal GTC with no circadian distribution. Neurologic examination was normal for
      all patients except for tremor of the hands similar to essential tremor, noted in
      35% of patients. Computed tomography (CT) brain scans were normal: 93% of
      patients had precipitating factors: sleep deprivation (89.5%), fatigue (73.7%),
      photosensitivity (36.8%; television and video games 8.8%), menstruation (24.1% of
      women), mental concentration (22.8%), and stress (12.3%). Incidence of JME among
      siblings (13 of 41 examined families) implies an autosomal recessive mode of
      inheritance for this Arab population. EEGs were frequently normal in treated
      patients. At least one abnormal EEG was recorded in 56 (84.9%) patients.
      Abnormalities consisted mainly of generalized discharges of spike/double spike
      and/or polyspike and slow wave. Frequent multiple spikes and discharge
      fragmentations varied from 0.5- to 20-s duration (mean 6.8 s). Twenty (30.3%) had
      focal abnormalities, and 18 (27.3%) had photoconvulsive discharges. Eighty-eight
      percent of patients remained seizure-free for > or = 3 years of follow-up.
      Effective treatment was achieved with valproate (VPA); control of myoclonic jerks
      was improved with clonazepam (CZP). CZP monotherapy did not consistently prevent
      GTC. Adding small doses of CZP with simultaneous reduction of VPA was the most
      effective and better tolerated form of medication, particularly in patients
      demonstrating an adverse reaction or requiring a large VPA dosage. VPA dosage was
      successfully reduced in 15 patients who were seizure-free for > 2 years and had
      infrequent seizures before treatment, but 9 of 11 patients relapsed after VPA
      discontinuation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8156947
TI  - Focal electroencephalographic abnormalities in juvenile myoclonic epilepsy.
AB  - A detailed study of EEGs of patients with an unequivocal diagnosis of juvenile
      myoclonic epilepsy (JME) showed a high prevalence of focal EEG abnormalities.
      Focal slow waves, spikes, and sharp waves and focal onset of the generalized
      discharge were present in 36.7% of EEGs in our patients with JME. In more than
      half of the patients, at least one EEG showed focal abnormalities. These features
      should not be misconstrued as indicative of partial epilepsy.

PMID- 8156948
TI  - Clinical and EEG asymmetries in juvenile myoclonic epilepsy.
AB  - We reviewed records of 85 patients with juvenile myoclonic epilepsy (JME) for
      significant asymmetries in clinical seizures or the EEG. We noted asymmetries in
      26 of 85 patients (30.6%). Only 2 patients had both clinical and EEG asymmetries;
      12 had clinical asymmetries and 12 had EEG asymmetries exclusively. Analysis of
      patients with and without asymmetries showed no statistically significant
      differences in comparisons of sex, age at seizure onset, family history of
      epilepsy, seizure type, or response to treatment. The delay in diagnosis was
      greater in JME patients with asymmetries (9.5 years) than in JME patients with no
      asymmetries (7.5 years), but this difference was not statistically significant.
      Fourteen of the 26 patients with asymmetries (53.8%) were initially misdiagnosed
      as having partial seizures. Asymmetries in JME patients are not only common, but
      are also a frequent cause of misdiagnosis.

PMID- 8156949
TI  - Video-polygraphic analysis of myoclonic seizures in juvenile myoclonic epilepsy.
AB  - We studied myoclonic seizures (MS) in 5 patients with juvenile myoclonic epilepsy
      (JME) using video polygraphic recordings to investigate the clinical
      characteristics of MS in this epileptic syndrome. The total number of MS analyzed
      was 302 (range 27-125, mean 60) seizures per patient. MS occurred either singly
      or repetitively (37 vs. 63%) and corresponded to generalized bilaterally
      synchronous single or multispike-and-wave complexes at 3-5 Hz. Video analysis of
      the myoclonic jerks demonstrated that either distal or proximal muscle
      involvement predominated. In the former, there was mild bilateral flexion and
      some external rotation of the forearms. In the latter, flexion of both arms at
      the elbow, flexion and abduction of the thighs, and extension of the back was
      observed. Asymmetry of MS was noted in 4 of 5 patients. Facial involvement of MS
      occurred infrequently in 2 patients. When the patients kept both arms
      outstretched, the arms dropped or there was sudden interruption of ongoing
      electromyographic (EMG) potentials immediately after myoclonic jerks
      (postmyoclonic inhibition) in all patients. One should inquire about these
      clinical characteristics of MS in JME when taking a thorough history in patients
      with primary generalized tonic-clonic seizures (GTC).

PMID- 8156950
TI  - Circling seizures in a case of juvenile myoclonic epilepsy.
AB  - Circling seizures (CS) have been described in association with focal lesions as
      well as with generalized EEG discharges. We report 1 patient with juvenile
      myoclonic epilepsy (JME) who developed CS. There were no focal findings on
      clinical examination, EEG, or imaging studies. We propose that CS in this patient
      may represent a profound asymmetry in expression of an idiopathic generalized
      epilepsy rather than a partial condition.

PMID- 8156951
TI  - Is HLA-DRW13 (W6) associated with juvenile myoclonic epilepsy in Arab patients?
AB  - In a study of 32 unrelated Arab patients with juvenile myoclonic epilepsy (JME),
      we compared the frequencies of human leukocyte antigen (HLA) class I and II
      alleles with those of unrelated healthy controls. A significant difference
      between the phenotypic frequencies in JME patients and controls was observed for
      DRW13, the split of DRW6 (37.5 vs 11% of controls). The strength of association
      as measured by the relative risk was 4.85 for this antigen (p = 0.002). The
      possible association of JME with HLA-DRW6 recently reported in Caucasians was
      confirmed in this study. This finding speaks for the homogeneity of the disease
      among Arabic and Caucasian JME patients. The existence of this association is
      evidence of a locus in the HLA region that influences expression of JME.

PMID- 8156952
TI  - Subclinical anterior horn cell involvement in juvenile myoclonic epilepsy.
AB  - Although clinical signs of muscle wasting and weakness were not present,
      electromyographic (EMG) evidence of subclinical anterior horn cell involvement of
      spinal cord was noted in 5 patients with juvenile myoclonic epilepsy (JME).
      Quantitative interference pattern analysis of EMG recorded from the anterior
      tibial muscle showed that the ratio (amplitude:turn/turn:second, A:T/T:S) was
      significantly increased in 10 patients with JME and 12 patients with lower motor
      neuron disorders (LMND) as compared with those of 22 normal subjects and 15
      patients with frequent generalized tonic-clonic seizures (GTC). Subclinical
      anterior horn cell involvement detected by EMG techniques can be related to a
      genetically determined component of JME.

PMID- 8156953
TI  - Vertebral arch nonfusion and juvenile myoclonic epilepsy.
AB  - Neural tube defects (NTD) are known to occur at a higher rate in pregnancies of
      women with epilepsy. Antiepileptic drugs (AEDs), notably valproate (VPA) and
      carbamazepine (CBZ), have been identified as risk factors, but a familial
      aggregation of this condition also occurs in the absence of pharmacologic
      teratogens. Spina bifida occulta, defined as a nonsymptomatic nonfusion of
      vertebral arches, has been suggested to be genetically determined, with an
      increased prevalence in patients with primary generalized epilepsy, and that the
      presence of this trait in fetal development can be enhanced pharmacologically to
      produce NTD such as meningomyelocele. In this study, plain abdominal radiographs
      were obtained from 56 patients with juvenile myoclonic epilepsy (JME) and 56 age-
      and sex-matched controls. The radiographs were presented in a random order to an
      unbiased radiologist. No difference in prevalence of vertebral arch nonfusion
      (VAN) was noted between the two groups. Even if it has no increased frequency in
      patients with epilepsy, however, VAN is a common radiologic finding, and its
      relation to symptomatic neural tube defects should be clarified in future
      studies.

PMID- 8156954
TI  - Stressful life events and seizure frequency in patients with epilepsy.
AB  - We tested whether unpleasant life events increased seizure occurrence in persons
      with epilepsy. Forty-six subjects maintained daily diaries for 10-36 weeks in
      which they recorded seizures and life events. Mean age of subjects was 39 years;
      78% were female; 83% had complex partial seizures (CPS). On the average, subjects
      reported 3.3 seizures a week. Analyses first were conducted within each subject
      and then in the sample overall. For each person, we tested whether seizure
      frequency increased within 24 h of the occurrence of unpleasant events, using
      Poisson regression analyses that adjusted for daily antiepileptic medication,
      sleep duration and quality, alcohol intake, menstrual status, and pleasant
      events. Rarity of events precluded analyses in 9 subjects. Events increased
      seizure frequency in 5 subjects (14%) (p < 0.05). Events decreased seizure
      frequency in 2 subjects (p < 0.05). When individual risk ratios were aggregated
      across subjects, unpleasant events were significantly associated with seizure
      increase only in men (RR = 1.67, 95% Confidence interval 1.09, 2.54). However,
      this finding must be interpreted with caution because of the limited number of
      men in the sample. In other aggregate analyses, events and seizures were not
      associated in subjects grouped by seizure type, age of seizure onset, current
      age, ethnicity, educational level, or marital status. Identification of factors
      that distinguish patients with and without event-triggered seizures requires
      further study.

PMID- 8156955
TI  - Use of alternative medicine by patients with epilepsy: a survey of 265 epileptic
      patients in a developing country.
AB  - We evaluated the use of alternative treatment methods, in various forms, by
      epileptic patients who had used these forms of treatment before seeking hospital
      treatment. Among the 265 epileptic patients, 47.6% used African traditional
      medicine alone: 24.1% combined traditional medicine with spiritual healing, 20.4%
      used spiritual healing alone, and 7.5% used other forms of alternative medicine.
      Patients used the alternative treatments for < 1 year to > 5 years before seeking
      hospital treatment, presumably when alternative medicine failed to control
      seizures. Relatives, friends, and neighbors had marked influence on the health
      seeking behavior of these epileptic patients: 86% of them were influenced to use
      alternative medicine. After initiation of hospital treatment, only 14.6% of
      patients who had earlier used African traditional medicine continued with such
      treatment; more than two thirds of the patients who had earlier used spiritual
      healing continued using such treatment, suggesting that many of these patients
      perceived some continuing benefits from these alternative treatments. This
      observation suggests that alternative medicine, especially spiritual healing,
      cannot be considered irrelevant in management of epilepsy in Africa. Further
      investigations are required to determine the efficacy, supportive role, and
      limitation of alternative medicine in management of epilepsy in developing
      countries.

PMID- 8156956
TI  - Partially successful treatment of Rasmussen's encephalitis with zidovudine:
      symptomatic improvement followed by involvement of the contralateral hemisphere.
AB  - An 18-year-old woman with a 4-year history of Rasmussen's encephalitis (RE)
      manifested by progressive aphasia, right hemiparesis, and nearly continuous
      intractable simple partial seizures that frequently secondarily generalized was
      treated with zidovudine (AZT). Seizures had not responded to any of the major
      antiepileptic drugs (AEDs) administered to high and toxic levels, or to ACTH. AZT
      was given for 62 days and discontinued because of granulocytopenia. Within 6
      weeks of AZT initiation, seizure stopped and neurologic deterioration was
      arrested for approximately 21 months. Subsequently, partial somatomotor seizures
      developed, affecting the previously uninvolved left hemibody. A 2-week repeat
      course of AZT was attempted, but unremitting fever and gastrointestinal (GI) side
      effects precluded continuation of AZT treatment. Spontaneous, sustained remission
      of seizures has not been reported in untreated RE. Seizure control and arrest of
      neurologic deterioration in this case outlasted use of AZT by 19 months. Because
      of the apparent response of this patient to AZT, clinical studies designed to
      assess long-term palliative/curative properties of antiviral agents, particularly
      in patients with involvement of the hemisphere dominant for language, appear
      warranted.

PMID- 8156957
TI  - Rapid arrest of seizures with an inhalation aerosol containing diazepam.
AB  - Diazepam (DZP) and a mixture of Chinese herbs customarily used to treat epilepsy
      were prepared as an aerosol under the trade name Aerosolum Diaiepami Compositae
      or Flvalscop (FVS). FVS was studied in a single-blind trial in 101 patients with
      seizures preceded by an aura and in 19 without an aura to whom was administered
      by another person. FVS or a control preparation was administered. In 16-22 s,
      (average 18.5 s), the aura was interrupted and no seizure ensued in 90% of the
      cases treated with FVS and in 26% of cases treated with the control preparation.
      Of the 120 patients, 8 had elementary partial seizures with Jacksonian march, 18
      had complex partial seizures (CPS), 7 had simple partial seizures with autonomic
      symptoms, and 87 had secondarily generalized tonic-clonic seizures. Eleven
      patients have now received FVS for 2 years (400 ml each). Forty patients for 1
      year (150-200 ml each); none of these patients have shown any side effects or
      abnormal laboratory findings. An aerosol-administered drug may be a valuable
      adjunct to the antiepileptic drug (AED) arsenal and merits more extensive
      evaluation.

PMID- 8156958
TI  - Lamotrigine in treatment of 120 children with epilepsy.
AB  - One hundred twenty children aged 10 months to 16 years 9 months were included in
      three studies with lamotrigine (LTG): a single-blind study (n = 60), a
      pharmacokinetic study (n = 23), and a compassionate group (n = 37). At 3 months,
      11 patients had become seizure-free and 34 had > 50% decrease in seizure
      frequency. The best results involved absence epilepsy, Lennox-Gastaut syndrome
      (LGS), and other symptomatic generalized epilepsy. Forty-two patients were
      followed > 1 year, 22 for a mean of 2.2 years, and there was no significant
      increase in seizure frequency as compared with 3-month follow-up. Fourteen
      patients became seizure-free for > 6 months; all except 1 had generalized
      epilepsy. For 12 patients, treatment could be reduced to monotherapy, but for
      those with valproate (VPA) comedication LTG dosage had to be increased; 25% of
      patients with VPA monotherapy exhibited skin rash, appearing 3-18 days after
      starting LTG. For 4 patients, LTG could be reintroduced after VPA was withdrawn.
      Ten patients had ataxia and/or drowsiness and 2 had vomiting. For all other
      patients, tolerance was excellent.

PMID- 8156959
TI  - Randomized, double-blind, placebo-controlled, clinical trial of D-alpha
      tocopherol (vitamin E) as add-on therapy in uncontrolled epilepsy.
AB  - In a double-blind, cross-over trial, vitamin E, and placebo were compared as add
      on therapy in 43 patients with uncontrolled epilepsy. The study consisted of a 3
      month baseline period followed by two treatment phases of vitamin E or placebo
      with cross-over to the second phase after 3 months. No significant side effects
      were noted during the study. Mean seizure frequency in the baseline period was
      15.9 +/- 10.5 as compared with 11.8 +/- 10.9 during the placebo phase and 13.7 +/
      11.1 during the vitamin E phase. No significant change in seizure frequency was
      observed with vitamin E as compared with placebo (p > 0.1). Similar observation
      was noted in subgroups with generalized seizures (n = 25), partial with
      secondarily generalized seizures (n = 11), or complex partial seizures (CPS) (n =
      7). This study did not corroborate the earlier claims of therapeutic efficacy of
      vitamin E as add-on therapy in refractory epilepsy in adults.

PMID- 8156960
TI  - Vigabatrin: clinical evidence supporting rational polytherapy in management of
      uncontrolled seizures.
AB  - Monotherapy is the policy for management of patients with epilepsy. With
      increasing knowledge of the biology of epilepsy and of the modes of action of
      antiepileptic drugs (AEDs), this concept must be reevaluated. When monotherapy
      fails to control seizures, subsequent treatment should be based on "rational
      pharmacology," taking into consideration the mode of action of the drugs, to
      provide improved efficacy with maintained tolerance and ease of administration.
      Introduction of vigabatrin (VGB) as a new AED calls for just such a reevaluation.
      VGB is an enzyme-activated irreversible inhibitor of gamma-aminobutyric acid
      (GABA)-transaminase that increases brain and cerebrospinal (CSF) GABA
      concentrations in animals and humans. It has limited efficacy in the classic
      animal seizure screening tests, but in many clinical studies has halved the
      incidence of seizures in approximately 50% of patients, especially those with
      partial epilepsies. We evaluated the efficacy of VGB in "socially integrated and
      active outpatients" as a likely subset to demonstrate any advantage of rational
      polytherapy. The criteria for this evaluation included the effects on seizure
      frequency, patient tolerability, and cognitive performance in a battery of
      psychometric tests. Fourteen of the 19 patients (73%) completing the study had >
      50% reduction in seizure frequency, and 10 of 19 (52%) had > 70% reduction in
      seizure frequency. Tolerability appeared good; somnolence was the most frequent
      adverse event. Three patients complained of a worsening of their seizures, 1 with
      an increase in frequency and 2 with development of myoclonic jerks not previously
      reported.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156962
TI  - Reversible valproate-induced extrapyramidal disorders.
AB  - We observed transient parkinsonism in 2 young epileptic patients with valproate
      (VPA) therapy. Complete recovery from extrapyramidal disorder occurred
      spontaneously in a few weeks. The lack of apparent susceptibility related to age
      and to VPA dosage, the rapid recovery from the extrapyramidal reaction, and the
      prevalence of negative signs such as bradykinesia and bradyphrenia can be
      considered the main clinical findings of this disease process. Pathophysiologic
      mechanisms of this rare "toxic" reaction remain unknown, although a transient
      imbalance between functionally reciprocal subgroups of GABA pathways leading to
      remediable dopamine inhibition might be hypothesized.

PMID- 8156961
TI  - Impact of valproate and phenytoin on cognitive function in elderly patients:
      results of a single-blind randomized comparative study.
AB  - Thirty-eight patients (median age 77 years; range 62-88 years) with elderly-onset
      seizures were entered into a single-blind, randomized study designed to compare
      the impact of phenytoin (PHT) and valproate (VPA) on cognitive function. A
      stratified minimization program matched the two groups for age, sex, and seizure
      type. Attention, concentration, psychomotor speed, and memory were assessed twice
      before treatment (to minimize practice effects), at 6 weeks and (for patients
      remaining in the study) at 3 months, 6 months, and 1 year by an extensive battery
      of psychologic tests. Changes in cognitive function were minor, and some tended
      toward improvement. Contrary to expectation, there was little difference between
      PHT and VPA with regard to impact on cognitive function. Frequent noncognitive
      adverse effects were reported. Thus, we did not replicate the findings of
      previous literature. We conclude that antiepileptic drug (AED) monotherapy as
      used in our trial did not produce significant adverse cognitive effects. The
      choice of AED in the elderly may therefore be more influenced by consideration of
      other adverse effects.

PMID- 8156963
TI  - Reflex sympathetic dystrophy associated with antiepileptic drugs.
AB  - Reflex sympathetic dystrophy syndrome (RSDS) complicating antiepileptic drug
      (AED) therapy is not well acknowledged in the neurologic literature. We report 4
      patients with reflex sympathetic dystrophy that occurred while they were
      receiving AEDs. All patients had shoulder and hand involvement, which in 2 was
      bilateral, and 1 had ipsilateral foot involvement. Two patients did not respond
      to a change in AEDs, but all improved with a course of prednisone. One patient
      with phenobarbital (PB)-associated RSDS relapsed on inadvertent rechallenge with
      secobarbital. A review of the literature showed that several other fibrosing
      disorders are associated with AED administration, including Dupuytren's
      contractures, frozen shoulder, plantar and hand nodules, and Peyronie's disease.
      RSD associated with AEDs is important to recognize because it may result in
      permanent disability if treatment is delayed.

PMID- 8156964
TI  - Circadian carbamazepine toxicity.
AB  - Owing to marked fluctuations in plasma concentrations, circadian CNS toxicity
      (maximum in the early afternoon) occurred in a 69-year-old female patient being
      treated with an instant-release formulation of carbamazepine (CBZ). The
      neurologic syndrome was reversible after administration of the same daily dose as
      sustained-release formulation. This case illustrates the importance of correct
      timing of blood sampling to detect drug-induced toxicity and of use of sustained
      release formulations in antiepileptic therapy with CBZ.

PMID- 8156965
TI  - Zonisamide-induced behavior disorder in two children.
AB  - Zonisamide (ZNS)-induced behavior disorders are reported in a 1-year-old girl and
      a 3-year-old boy. Both patients, who had no previous developmental or mental
      problems, displayed secondarily generalized motor seizures. Serum concentrations
      of ZNS were not high, 8.8 and 12.3 micrograms/ml (effective range 10-30
      micrograms/ml) respectively. Although many cases of ZNS-related psychotic
      reactions and/or behavior disorders have been reported, all affected patients had
      complex partial seizures (CPS) and had received combination therapy with
      phenytoin (PHT). Thus, whether the disorders were induced only by ZNS, by an
      interaction between ZNS and PHT, or by CPS could not be determined. In the
      children reported, however, ZNS clearly induced behavior disorders at plasma ZNS
      levels within or even below the therapeutic range.

PMID- 8156966
TI  - Determination of valproate in the presence of felbamate in human plasma by narrow
      bore capillary gas chromatography.
AB  - A narrow bore capillary gas chromatographic method with one extraction step has
      been developed for quantitation of valproate (VPA) in the presence of felbamate
      (FBM) in human plasma. The method uses 0.250-ml aliquots of human plasma and one
      internal standard (IS). Chromatographic conditions include a DBWAX, 0.25 mm ID x
      15 m, 0.25-micron film thickness column; splitless injection; and flame
      ionization detection. The linear quantitation range for VPA is 1.00-256
      micrograms/ml.

PMID- 8156967
TI  - Quantum pharmacologic studies applicable to the design of anticonvulsants:
      theoretical conformational analysis and structure-activity studies of
      barbiturates.
AB  - We report the first large-scale systematic quantitative structure-activity
      relationship (QSAR) study of barbiturates, correlating molecular structures with
      anticonvulsant activity. To achieve this QSAR study, we devised a four-step
      strategy. In step 1, an optimal quantum mechanical technique for determining the
      geometry and shape (conformation) of barbiturates was ascertained; this is the
      AM1 semiempirical molecular orbital method. In step 2, the AM1 method was used to
      optimize the structures and molecular properties of 48 barbiturates with varying
      anticonvulsant activity. In step 3, discriminant analysis and regression analysis
      statistical calculations were used to correlate the molecular properties of the
      48 analogues against maximal electroshock (MES) and subcutaneous metrazol
      (s.c.Met)-induced seizures. In step 4, the contribution of molecular
      electrostatic properties to barbiturate anticonvulsant activity was further
      refined by quantum mechanical derived molecular electrostatic potential (MEP)
      maps. Using this four-step strategy, we defined the pharmacophore, the portion of
      a molecule responsible for bioactivity, for anti-MES and anti-s.c.Met activity.
      For anti-s.c.Met activity, barbiturate lipophilicity and geometry are important
      considerations; for anti-MES activity, barbiturate topologic and electronic
      properties have increased relevance.

PMID- 8156968
TI  - Effect of a gamma-aminobutyric acid uptake inhibitor, NNC-711, on spontaneous
      postsynaptic currents in cultured rat hippocampal neurons: implications for
      antiepileptic drug development.
AB  - The effect of a novel gamma-aminobutyric acid (GABA) uptake inhibitor, NNC-711,
      on spontaneous postsynaptic currents was studied in cultured rat hippocampal
      neurons by the whole cell patch clamp method. NNC-711 decreased the amplitude of
      inhibitory postsynaptic currents (IPSCs) and did not prolong the decay. NNC-711
      also decreased the amplitude of excitatory PSCs (EPSCs). The GABAB receptor
      antagonist 2-OH saclofen abolished the effect on both IPSCs and EPSCs. NNC-711
      itself induced no current and had no effect on currents induced by exogenously
      applied GABA. These findings suggest that duration of GABAA-receptor mediated
      IPSCs is not determined by GABA uptake and that GABA uptake inhibitors may work
      by allowing GABA to remain in the synaptic area long enough to activate
      presynaptic GABAB receptors.

PMID- 8156969
TI  - Nuclear magnetic resonance detection of increased cortical GABA in vigabatrin
      treated rats in vivo.
AB  - 1H Nuclear magnetic resonance ([1H]NMR) spectroscopy was used to detect elevation
      of gamma-aminobutyric acid (GABA) in rat brain after administration of the
      antiepileptic drug vigabatrin (VGB). Rats were treated for 3 weeks with VGB added
      to their drinking water to deliver a dose of 250 mg/kg body weight per day. NMR
      spectroscopy was performed noninvasively in vivo, and a GABA concentration of 6.0
      +/- 2.3 mmol/kg wet weight (mean +/- SD, n = 5) was measured. GABA could not be
      detected in control animals in vivo. Postmortem GABA levels of 1.3 +/- 0.5 and
      4.5 +/- 1.0 mmol/kg (mean +/- SD, n = 5) were measured in perchloric acid
      extracts of frozen brain from control and treated animals, respectively.
      Noninvasive measurement of increased cerebral GABA should allow detailed studies
      of the pharmacology of GABA-increasing drugs in vivo. With future developments,
      these measurements may be feasible in human subjects.

PMID- 8156970
TI  - Dose-response relationships with nimodipine against electroshock seizures in
      mice.
AB  - The anticonvulsant effect of the dihydropyridine calcium channel blocker,
      nimodipine (NMD) was evaluated against electroshock-induced seizures in mice. At
      1 h postdosing, NMD elicited a dose-dependent reduction in the occurrence of
      tonic hindlimb extension (THE) after maximal electroshock (MES). The calculated
      ED50 for NMD was 87 mg/kg. A single dose of NMD (75 mg/kg) produced a significant
      (p < 0.05) reduction in occurrence of THE for < or = 12 h postdosing. NMD was
      detectable for < or = 6 h, and plasma and brain drug concentrations correlated
      well (r = 0.677, p < 0.01) for that period. At 1 h postdose, a single dose of NMD
      (75 mg/kg) produced a 40% increase (p < 0.001) in the threshold for tonic
      seizures as determined by minimal electroshock (Min-ES). NMD is an effective
      anticonvulsant against experimental seizures induced by electroshock. The
      pharmacodynamic effect of NMD appears to extend beyond the time anticipated from
      the pharmacokinetic profile.

PMID- 8156971
TI  - Calcium channel blockers verapamil and nimodipine inhibit kindling in adult and
      immature rats.
AB  - The calcium channel blockers verapamil (VPM) and nimodipine (NMD) were
      administered to adult or immature (16-day-old) rats to determine their effects on
      amygdala-kindled seizures. The afterdischarge threshold (ADT) kindling rate and
      degree of postictal refractoriness were determined for two doses of VPM (0.5 and
      5.0 mg/kg in rat pups and 2 and 10 mg/kg in adult rats) or 30 mg/kg nimodipine
      (NMD). Neither VPM nor NMD affected the ADT of the amygdala in adult or immature
      rats. VPM retarded the rate of kindling in both adult and immature rats in a dose
      dependent manner; the number of stimulations required to progress through seizure
      stages were increased. NMD 30 mg/kg reduced the kindling rate and AD duration in
      both adult and immature rats. Neither drug was able to suppress recurrent
      seizures elicited by repetitive stimulation. These results suggest that
      verapamil, and possibly NMD may be of clinical utility in treatment of epilepsy,
      especially complex partial seizures.

PMID- 8156972
TI  - Topiramate: preclinical evaluation of structurally novel anticonvulsant.
AB  - Topiramate [TPM, 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose
      sulfamate] (RWJ-17021-000, formerly McN-4853) is a structurally novel
      antiepileptic drug (AED). The preclinical anticonvulsant profile suggests that
      TPM acts primarily by blocking the spread of seizures. TPM was highly effective
      in the maximal electroshock (MES) seizure test in rats and mice. Activity was
      evident < or = 0.5 h after oral administration and lasted at least 16 h. The ED50
      values 4 h after oral dosing were 13.5 and 40.9 mg/kg in rats and mice,
      respectively. TPM blocked pentylenetetrazol (PTZ)-induced clonic seizures at high
      doses in mice (ED50 = 1,030 mg/kg orally, p.o.). With motor incoordination and
      loss of righting reflex used as indicators of neurologic impairment, the
      neuroprotective index (TD50/MES ED50) for TPM was equivalent or superior to that
      of several approved AEDs. In mice pretreated with SKF-525A (a P450 enzyme
      inhibitor), the anticonvulsant potency was either increased or unaffected when
      TPM was tested 0.5, 1, or 2 h after i.p. administration, suggesting that TPM
      rather than a metabolite was the active agent. In mice pretreated with reserpine
      or tetrabenazine, the activity of TPM in the MES test was markedly reduced. TPM
      was inactive in a variety of receptor binding, neurotransmitter uptake, and ion
      channel tests. TPM weakly inhibited erythrocyte carbonic anhydrase (CA) activity.
      However, the anticonvulsant activity of TPM appears to differ mechanistically
      from that of acetazolamide.

PMID- 8156973
TI  - Clinical pharmacology and pharmacokinetics of oxcarbazepine.
AB  - Oxcarbazepine (OCBZ) is a new antiepileptic drug (AED) structurally related to
      carbamazepine (CBZ) but differing in several important aspects, notably
      metabolism and induction of metabolic pathways. Consequently, OXCB has fewer drug
      drug interactions compared with CBZ. Absorption of OCBZ is rapid and complete. In
      animals it is responsible for the pharmacological effect. In humans, however, the
      parent compound is rapidly and extensively metabolized to a monohydroxy
      derivative (MHD), which is responsible for the therapeutic effect. Exposure to
      the MHD increases dose proportionally, and steady state is achieved after only
      three or four doses in a twice-daily regimen. When given with food, systemic
      exposure to MHD increases by about 17%. MHD is eliminated with a half-life of
      about 8-10 h. About 27% of the dose is recovered in the urine as unchanged MHD
      and a further 49% as a glucuronide conjugate of MHD. Results suggest that the
      kinetics of OCBZ should not be affected by impaired liver function. Impaired
      kidney function does not affect the kinetics of MHD; the glucuronide conjugate
      will, however, accumulate in these patients. The conversion of OCBZ to MHD is
      catalyzed by reductase enzymes, which are not subject to induction. Furthermore,
      OCBZ itself does not appear to induce the cytochrome P-450 family in general,
      although it does induce the P-450 IIIA subfamily, which is responsible for the
      metabolism of estrogens and the dihydropyridine calcium-channel blockers (e.g.,
      nifedipine, felodipine). In patients, linear and dose-proportional kinetics with
      no autoinduction of metabolism simplify OCBZ dosage adjustment.

PMID- 8156974
TI  - Oxcarbazepine: pharmacokinetic interactions and their clinical relevance.
AB  - Antiepileptic drug (AED) interactions are a common problem during epilepsy
      treatment. Oxcarbazepine (OCBZ) is a keto homologue of carbamazepine (CBZ) with a
      completely different metabolic profile. In humans, the keto group is rapidly and
      quantitatively reduced to form a monohydroxy derivative (MHD), which is the main
      active agent during OCBZ therapy. MHD is eliminated by renal excretion,
      glucuronidation and, marginally, by hydroxylation to a diol derivative. This
      metabolic profile, and in particular the limited involvement of oxidative
      microsomal enzymes, suggests that OCBZ may have fewer drug interactions compared
      with traditional AEDs. This possibility has been investigated in experimental
      studies and, retrospectively, in data obtained from clinical trials. The capacity
      of OCBZ to induce microsomal enzymes of the P-450 family has mostly been examined
      by use of antipyrine and CBZ kinetics as markers. The results suggest that OCBZ
      has little enzyme inducing capacity. In clinical trials in which OCBZ was
      substituted for CBZ, plasma concentrations of concomitant AEDs were increased,
      possibly as a consequence of total or partial de-induction. OCBZ interference
      with other drugs has been evaluated for warfarin, felodipine, and oral
      contraceptives, three medications strongly influenced by enzyme-inducing AEDs.
      OCBZ does not modify the anticoagulant effect of warfarin, whereas some reduction
      in felodipine concentration and a clinically significant reduction of
      contraceptive drug levels and efficacy were observed. Polytherapy with
      established AEDs does not significantly modify OCBZ disposition (MHD kinetics);
      however, available information is not extensive. Finally, the action on OCBZ
      kinetics of a group of drugs (verapamil, cimetidine, erythromycin,
      dextropropoxyphene, and viloxazine) known to inhibit the metabolism of some AEDs
      has been studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8156975
TI  - Clinical development outlook of oxcarbazepine.
AB  - Oxcarbazepine (OCBZ) has been accepted for registration as a first-line
      antiepileptic drug (AED) in several countries. However, because of changing
      regulations, further studies confirming statistically significant proof of
      efficacy are necessary in accordance with new standards. Therefore, Ciba has
      initiated a worldwide clinical development program to achieve registration. Four
      different types of design to demonstrate statistically significant proof of
      efficacy in partial seizures will be initiated. These studies are a "classical"
      polytherapy add-on study, a monotherapy substitution trial, a high-dose/low-dose
      active-control monotherapy study, and a study in presurgical patients.

PMID- 8156976
TI  - Clinical experience with oxcarbazepine.
AB  - Controlled studies of oxcarbazepine (OCBZ) and the largest of the open studies of
      OCBZ were reviewed. The overall results indicated that OCBZ has the same clinical
      effect as carbamazepine (CBZ) but causes fewer adverse effects. Studies of
      allergic toxicity seem to indicate that OCBZ may be tolerated in the majority of
      patients developing allergy towards CBZ. We concluded that OCBZ is a drug of
      first choice for the treatment of epilepsy.

PMID- 8156977
TI  - Practical aspects of oxcarbazepine treatment.
AB  - In patients with refractory seizures, substitution of oxcarbazepine (OCBZ) for
      carbamazepine (CBZ) may be associated with reduced seizure frequency and an
      improved mental state. The recommended dosage of OCBZ as monotherapy for adults
      with epilepsy is 600-1,200 mg orally per day but may be higher in patients with
      refractory seizures and in patients requiring combination therapy. When OCBZ is
      substituted for ongoing CBZ therapy, it is possible to change the dosage
      immediately so that the patient finishes treatment with CBZ on one day and starts
      with a full dosage of OCBZ on the next day, even when the full dosage is 50%
      greater in milligrams than the corresponding CBZ dosage. Allergic skin reactions
      are rare, and crossreactivity is seen in about 25% of patients hypersensitive to
      CBZ. Hyponatremia after the use of OCBZ is usually benign, as long as the acute
      water intoxication is effectively treated. Because of its pharmacokinetic
      advantages and efficacy, we believe OCBZ is better than CBZ. We therefore
      consider OCBZ as the drug of first choice for conditions in which CBZ is
      currently indicated.

PMID- 8156978
TI  - Oxcarbazepine: mechanisms of action.
AB  - The antiepileptic drug (AED) oxcarbazepine (OCBZ) and its rapidly formed 10
      monohydroxy metabolite (MHD) protect against electroshock-induced tonic hindlimb
      extension in rodents (ED50 14-21 mg/kg p.o.). Both stereoisomers of MHD also
      protect. As with carbamazepine (CBZ), these findings suggest clinical efficacy
      against generalized tonic-clonic and, to some extent, partial seizures. OCBZ
      (IC50 5 x 10(-8) M), MHD (IC50 2 x 10 (-8) M), and CBZ (IC50 6 x 10(-7) M) limit
      the frequency of firing of sodium-dependent action potentials by cultured mouse
      central neurons and reduce Vmax progressively in a use-dependent manner at
      concentrations below therapeutic plasma concentrations in OCBZ-treated patients.
      This suggests that blockade of voltage-sensitive sodium channels could contribute
      to the antiepileptic efficacy of OCBZ. Blockade of penicillin-induced
      epileptiform discharges in hippocampal slices by MHD and its stereoisomers was
      diminished when the potassium channel blocker 4-aminopyridine was added to the
      bath fluid. This indicates that additional mechanisms of action, e.g., an effect
      on potassium channels, might be clinically important. In addition, both
      stereoisomers are equally responsible for the antiepileptic activity of the
      racemate, i.e., MHD, and are therefore likely to play a therapeutic role. Such
      actions could confer broad clinical utility on OCBZ.

PMID- 8156979
TI  - The bioimpedance 'craze'.

PMID- 8156980
TI  - Isomeric fatty acids and human health.

PMID- 8156981
TI  - The nutritional impact of seasonality in children and adults of rural Ethiopia.
AB  - A survey of the nutritional status of subsistence farmers was conducted over 13
      months in a rural area of Ethiopia characterized by moderate climatic seasonality
      and intensive land exploitation. Bi-monthly questionnaires on food consumption,
      time allocation, agricultural production and cash flow were administered to 203
      households and anthropometry performed on 1407 individuals. Comparison of post
      harvest and pre-harvest anthropometry was made on 672 individuals (48% of the
      sample). In children, seasonal changes in the Z-score of weight-for-height were
      small and not significant. Height growth velocity showed instead a marked
      seasonal pattern, with values close to normal (-0.2 SD units) in July to
      December, a period characterized by better food availability, and lower values (
      3.0 SD units) in January to June, a period characterized by intensive farm labour
      and heavy rains. Among the adults, body weight was highest in the post-harvest
      season (December) and decreased by 1.5 +/- 2.3 kg in men and 1.3 +/- 2.6 kg in
      women to the yearly minimum in the pre-harvest season (June). The paper shows
      that in this area children and adults both suffer from exposure to seasonal
      energy stress. The change in weight-for-height Z-score observed in children and
      the body weight loss observed in adults was greater in individuals of low socio
      economic status and, within the same socio-economic level, in individuals with
      better nutritional status.

PMID- 8156982
TI  - Seasonal energy stress in an Ethiopian rural community: an analysis of the impact
      at the household level.
AB  - The household integrated response to seasonal fluctuations in food availability
      and work load was assessed in a longitudinal study in two villages of southern
      Ethiopia. The household response to energy stress was estimated by pooling weight
      changes of all members of the family, accounting for the diverse biological and
      functional meaning of weight losses of different age and sex groups, and levels
      of nutritional status. On average, seasonal energy stress experienced by the
      households was modest (3.3%, P < 0.05 by Tukey test). The cumulative weight
      change of poor households was twice as large as that of rich ones, and evidence
      was obtained of their further deterioration over the following agricultural year.
      Household food availability fluctuated seasonally, with evident socio-economic
      gradient: in the early pre-harvest season food stocks of poor households were 6.5
      times smaller than those of better-off families (P < 0.001 by ANOVA). Unlike rich
      households, poor families markedly decreased the time devoted to agriculture in
      the pre-harvest season. Crop selection, quality of land management and time
      employed in agricultural work might have synergistically concurred to cause the
      stress situation.

PMID- 8156983
TI  - A five-compartment model of body composition of healthy subjects assessed using
      in vivo neutron activation analysis.
AB  - A body composition study of 31 healthy subjects covering a wide range of age
      (23.5-72.0 years) and weight (44.5-104.2 kg) has been undertaken. Subjects were
      assessed by in vivo neutron activation and tritiated water analysis and values of
      total body nitrogen, hydrogen and fat obtained by utilization of a five
      compartment model of body composition comprising protein, water, fat, minerals
      and glycogen. The protein (as 6.25 x nitrogen) and water compartments were
      measured but the smaller compartments of minerals and glycogen were calculated as
      fixed fractions of the fat-free mass estimated from the water space. Fat was
      calculated as the body mass less the sum of the four other compartments. Mean
      values (+/- SEM), expressed as a percentage of body mass, for nitrogen, hydrogen
      and fat were 2.56 (+/- 0.07)%, 10.07 (+/- 0.04)%, and 21.9 (+/- 1.7)%
      respectively for men and 2.14 (+/- 0.07)%, 10.40 (+/- 0.04)%, and 35.5 (+/- 1.7)%
      respectively for women. The accuracy of the nitrogen measurements was evaluated
      by comparison with calculated values from two prediction equations; correlation
      coefficients, the mean bias (estimated from the mean differences between the
      measured and predicted nitrogen), the confidence interval for the bias, and
      limits of agreement were calculated. The correlation coefficients were high (r >
      0.93) and the mean bias indicative of agreement. The ratio of nitrogen to the fat
      free mass (derived from the body composition model) was also calculated and mean
      values (+/- SEM) of 32.7 (+/- 0.4) and 33.1 (+/- 0.4) g/kg for men and women,
      respectively were obtained. The hydration of the fat-free mass was determined to
      be 0.725 (+/- 0.002) and 0.722 (+/- 0.002) kg/kg for men and women respectively.
      The accuracy of the body fat estimate was evaluated by comparison with skinfold
      thickness-derived values and computation from tritiated water space. The ratio of
      the body composition model to skinfold-thickness-derived fat was significantly (P
      < 0.005) greater than unity. The mean bias between the body composition model and
      tritiated-water-derived fat was -0.6 percentage points of fat (95% confidence
      interval from -0.3 to -0.9 percentage points of fat). Finally a prediction
      equation (r2 = 0.908, SEE = 108 g) for body nitrogen in healthy subjects based on
      weight, age and sex was calculated.

PMID- 8156984
TI  - Duration of the inhibitory effect of calcium on non-haem iron absorption in man.
AB  - We investigated the duration of the inhibitory effect of calcium from milk and
      cheese (340 mg) in a breakfast meal on non-haem iron absorption from a hamburger
      meal eaten 2 or 4 h after the breakfast. The effect of calcium on iron absorption
      was studied in 21 human subjects by using paired observations and a dual
      radioisotope method (55Fe and 59Fe). No duration effect of calcium on iron
      absorption was observed in this study. The present findings offer an opportunity
      for theoretical improvement of iron nutrition by a redistribution of the daily
      intake of calcium to the meals with a minor iron content, i.e. breakfast and the
      evening meal.

PMID- 8156985
TI  - Nursing frequency and the energy intake from breast milk and supplementary food
      in a rural Thai population: a longitudinal study.
AB  - A group of 60 infants representative of a rural Thai population were studied
      longitudinally over the first year of life. Their breast milk intake,
      supplementary food intake and nursing patterns were measured for 2 consecutive
      days at about 15, 45, 90, 180, 270 and 360 days of age. For the sample as a
      whole, the estimated peak value for energy intake from breast milk was 529 kcal
      (2213 kJ) and occurred at 34 days post-partum. Thereafter milk intake declined,
      with 40% of infants fully weaned by the end of the first year. Supplements were
      introduced early, with 15% of infants supplemented by 2 weeks and 68% by 6 weeks.
      Higher levels of supplementation were associated with lower breast milk intake.
      In addition there was an independent positive effect of nursing patterns (number
      of breast feeds per day). Interaction terms show that both supplementary feeding
      and number of feeds have quantitatively different effects at different ages:
      breast milk intake varies more with level of supplementation in younger infants
      than in older infants, and varies more with number of feeds in older infants than
      in younger infants. Higher peak levels of breast milk intake were followed by a
      steeper decline, and infants who took more breast milk at 15 days were more
      likely to be fully weaned by their first birthday.

PMID- 8156986
TI  - Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA
      methyltransferase from E. coli.
AB  - The mutagenic and carcinogenic effects of simple alkylating agents are mainly due
      to methylation at the O6 position of guanine in DNA. O6-methylguanine directs the
      incorporation of either thymine or cytosine without blocking DNA replication,
      resulting in GC to AT transition mutations. In prokaryotic and eukaryotic cells
      antimutagenic repair is effected by direct reversal of this DNA damage. A
      suicidal methyltransferase repair protein removes the methyl group from DNA to
      one of its own cysteine residues. The resulting self-methylation of the active
      site cysteine renders the protein inactive. Here we report the X-ray structure of
      the 19 kDa C-terminal domain of the Escherichia coli ada gene product, the
      prototype of these suicidal methyltransferases. In the crystal structure the
      active site cysteine is buried. We propose a model for the significant
      conformational change that the protein must undergo in order to bind DNA and
      effect methyl transfer.

PMID- 8156987
TI  - Macromolecular chelation as an improved mechanism of protease inhibition:
      structure of the ecotin-trypsin complex.
AB  - The 2.4 A crystal structure (R = 0.180) of the serine protease inhibitor ecotin
      was determined in a complex with trypsin. Ecotin's dimer structure provides a
      second discrete and distal binding site for trypsin and, as shown by modelling
      experiments, other serine proteases. The second site is approximately 45 A from
      the reactive/active site of the complex and features 13 hydrogen bonds, including
      six that involve carbonyl oxygen atoms and four bridged by water molecules.
      Contacts ecotin makes with trypsin's active site are similar to, though more
      extensive than, those found between trypsin and basic pancreatic trypsin
      inhibitor. The side chain of ecotin Met84 is found in the substrate binding
      pocket of trypsin where it makes few contacts, but also does not disrupt the
      solvent structure or cause misalignment of the scissile bond. This first case of
      protein dimerization being used to augment binding energy and allow chelation of
      a target protein provides a new model for protein-protein interactions and for
      protease inhibition.

PMID- 8156988
TI  - Uranyl photoprobing of a four-way DNA junction: evidence for specific metal ion
      binding.
AB  - Metal ions are very important in mediating the folding of nucleic acids, as
      exemplified by the folding of the four-way DNA junction into the stacked X
      conformation. Uranyl ion-mediated photocleavage provides a method for the
      localization of high-affinity ion binding sites in nucleic acids, and we have
      applied this to the four-way DNA junction. We have made the following
      observations. (i) Uranyl ions (UO2(2+)) suppressed the reactivity of junction
      thymine bases against attack by osmium tetroxide, indicating that the uranyl ion
      induces folding of the junction into a stacked conformation. (ii) DNA located
      immediately at the point of strand exchange on the two exchanging strands was
      hypersensitive to uranyl photocleavage. The relative hypersensitivity was
      considerably accentuated when the photocleavage was carried out in the presence
      of citrate ions. This suggests the presence of a tight binding site for the
      uranyl ion in the junction. (iii) The same positions were significantly protected
      from uranyl cleavage by the presence of hexamminecobalt (III) or spermidine.
      These ions are known to induce the folded conformation of the four-way junction
      with high efficiency, suggesting a direct competition between the ions. By
      contrast, magnesium ions failed to generate a similar protection against
      photocleavage. These results suggest that the uranyl, hexamminecobalt (III) and
      spermidine ions compete for the same high affinity binding site on the junction.
      This site is located at the centre of the junction, at the point where the
      exchanging strands pass between the stacked helices. We believe that we have
      observed the first known example of a metal ion 'footprint' on a folded nucleic
      acid structure.

PMID- 8156989
TI  - Model for a DNA-mediated synaptic complex suggested by crystal packing of gamma
      delta resolvase subunits.
AB  - The packing arrangement of the 12 subunits of intact gamma delta resolvase in the
      unit cell of a hexagonal crystal form suggests a model for site-specific
      recombination that involves a DNA-mediated synaptic intermediate. The crystal
      structure has been determined by molecular replacement and partially refined at
      2.8/3.5 A resolution. Although the small DNA-binding domain is disordered in
      these crystals, packing considerations show that only a small region of space in
      the crystal could accommodate a domain of its size. A family of related models
      for a synaptic complex between two DNA duplexes and 12 monomers that are arranged
      as situated in the crystal is consistent with the known topology of the complex
      and the distances between the three resolvase dimer-binding sites per DNA;
      further, these models place the two DNA recombination sites in contact with each
      other between two resolvase dimers, implying that strand exchange is accomplished
      through direct DNA-DNA interaction. A major role postulated, then, for the
      resolvase protein assembly is to stabilize a res DNA structure that is close to
      the topological transition state of the reaction.

PMID- 8156991
TI  - The HimA and HimD subunits of integration host factor can specifically bind to
      DNA as homodimers.
AB  - Integration host factor (IHF) is a heterodimeric protein from Escherichia coli
      which specifically binds to an asymmetric consensus sequence. We have isolated
      the individual subunits of IHF, HimA and HimD, and show that an active IHF
      protein can be reconstituted from these subunits. The HimA and HimD polypeptides
      alone are capable of specifically recognizing the same ihf sequence. The
      mobilities of the protein-DNA complexes in a gel-retardation assay suggest that
      the proteins bind as homodimers. The stability of the HimD-DNA complex is
      approximately 100-fold lower than that of the IHF-DNA complex. The HimA-DNA
      complex is even less stable and is only observed when a large excess of HimA is
      used. This instability is possibly due to the inability of HimA to form stable
      homodimers. By domain swapping between HimA and HimD, we have constructed an IHF
      fusion protein which has the putative DNA-binding domains of only HimA. This
      fusion protein forms stable dimers and makes specific protein-DNA complexes with
      a high efficiency. A comparable fusion protein with only the DNA-binding domains
      of HimD forms less stable complexes, suggesting that sequence-specific contacts
      between IHF and the ihf consensus are mainly provided by the HimA subunit.

PMID- 8156990
TI  - Specific binding of HIV-1 nucleocapsid protein to PSI RNA in vitro requires N
      terminal zinc finger and flanking basic amino acid residues.
AB  - The nucleocapsid (NC) protein of human immunodeficiency virus HIV-1 (NCp7) is
      responsible for packaging the viral RNA by recognizing a packaging site (PSI) on
      the viral RNA genome. NCp7 is a molecule of 55 amino acids containing two zinc
      fingers, with only the first one being highly conserved among retroviruses. The
      first zinc finger is flanked by two basic amino acid clusters. Here we
      demonstrate that chemically synthesized NCp7 specifically binds to viral RNA
      containing the PSI using competitive filter binding assays. Deletion of the PSI
      from the RNA abrogates this effect. The 35 N-terminal amino acids of NCp7,
      comprising the first zinc finger, are sufficient for specific RNA binding.
      Chemically synthesized mutants of the first zinc finger demonstrate that the
      amino acid residues C-C-C/H-C/H are required for specific RNA binding and zinc
      coordination. Amino acid residues F16 and T24, but not K20, E21 and G22, located
      within this zinc finger, are essential for specific RNA binding as well. The
      second zinc finger cannot replace the first one. Furthermore, mutations in the
      basic amino acid residues flanking the first zinc finger demonstrate that R3, 7,
      10, 29 and 32 but not K11, 14, 33 and 34 are also essential for specific binding.
      Specific binding to viral RNA is also observed with recombinant NCp15 and
      Pr55Gag. The results demonstrate for the first time specific interaction of a
      retroviral NC protein with its PSI RNA in vitro.

PMID- 8156992
TI  - Conjugative transposition: Tn916 integrase contains two independent DNA binding
      domains that recognize different DNA sequences.
AB  - Transposition of the conjugative transposon Tn916 requires the activity of a
      protein, called Int, which is related to members of the integrase family of site
      specific recombinases. This family includes phage lambda integrase as well as the
      Cre, FLP and XerC/XerD recombinases. Different proteins, consisting of fragments
      of Tn916 Int protein fused to the C-terminal end of maltose binding protein (MBP)
      were purified from Escherichia coli. DNase I protection experiments showed that
      MBP-INT proteins containing the C-terminal end of Int bound to the ends of the
      transposon and adjacent plasmid DNA. MBP-INT proteins containing the N-terminal
      end of Int bound to sequences within the transposon close to each end.
      Competition binding experiments showed that the sites recognized by the C- and N
      terminal regions of Int did not compete with each other for binding to MBP-INT.
      We suggest that Tn916 and related conjugative transposons are unique among
      members of the integrase family of site-specific recombination systems because
      the presence of two DNA binding domains in the Int protein might allow Int to
      bridge recombining sites, and this bridging seems to be the sole mechanism
      ensuring that only correctly aligned molecules undergo recombination.

PMID- 8156993
TI  - Cdc25A is a novel phosphatase functioning early in the cell cycle.
AB  - The cdc25+ tyrosine phosphatase is a key mitotic inducer of the fission yeast
      Schizosaccharomyces pombe, controlling the timing of the initiation of mitosis.
      Mammals contain at least three cdc25+ homologues called cdc25A, cdc25B and
      cdc25C. In this study we investigate the biological function of cdc25A. Although
      very potent in rescuing the S.pombe cdc25 mutant, cdc25A is less structurally
      related to the S.pombe enzyme. Northern and Western blotting detection reveals
      that unlike cdc25B, cdc25C and cdc2, cdc25A is predominantly expressed in late
      G1. Moreover, immunodepletion of cdc25A in rat cells by microinjection of a
      specific antibody effectively blocks their cell cycle progression from G1 into
      the S phase, as determined by laser scanning single cell cytometry. These results
      indicate that cdc25A is not a mitotic regulator but a novel phosphatase that
      plays a crucial role in the start of the cell cycle. In view of its strong
      ability to activate cdc2 kinase and its specific expression in late G1, cdc2
      related kinases functioning early in the cell cycle may be targets for this
      phosphatase.

PMID- 8156994
TI  - Nuclear localization of p85s6k: functional requirement for entry into S phase.
AB  - Immunolocalization of a newly described isoform of p70s6k, termed p85s6k,
      demonstrated a predominantly nuclear location in rat embryo fibroblasts (REF-52),
      a compartment in which growth factor-mediated phosphorylation of S6 has recently
      been reported. Microinjection of expression vectors encoding either p85s6k or a
      fusion protein containing only the putative nuclear localization motifs led to
      the exclusive accumulation of both products in the nucleus. Consistent with such
      a localization, microinjection of affinity-purified anti-p85s6k IgG into the
      nucleus, but not the cytoplasm, blocked serum-induced initiation of DNA
      synthesis. Co-injection into the nucleus of the anti-p85s6k IgG with activated
      p70s6k, which lacks the antigenic epitope, rescued the S phase block, arguing
      that the antibody exerts its effects through inhibiting p85s6k function. The
      results indicate a novel role for S6 phosphorylation in the nucleus distinct from
      that in the cytoplasm, a role essential for mitogenesis.

PMID- 8156995
TI  - A developmental checkpoint couples the initiation of sporulation to DNA
      replication in Bacillus subtilis.
AB  - Spore formation in Bacillus subtilis requires the generation of two distinct cell
      types, each with an active chromosome that becomes committed to a defined program
      of gene expression. Here we show that a developmental checkpoint couples the
      initiation of sporulation, and the subsequent formation of these two cell types,
      to DNA replication early during development. Inhibiting the initiation of
      chromosomal replication prevents the onset of sporulation and inhibits expression
      of several genes that are normally induced early during development. This defect
      in gene expression is due to inhibition of the multi-component phosphorylation
      pathway needed to activate the developmental transcription factor encoded by
      spo0A. The target affected by inhibiting the initiation of replication is neither
      Spo0A nor the major kinase, KinA, needed for production of Spo0A approximately P.
      Rather, the target appears to be one of the proteins that transfers phosphate
      from the kinase to the Spo0A transcription factor. The signal that couples
      activity of the phosphorelay to the initiation of DNA replication is different
      from the previously described DNA damage signal that inhibits the phosphorelay
      during SOS induction in a recA-dependent response. Thus, DNA replication as well
      as DNA damage signals control production of Spo0A approximately P and initiation
      of sporulation.

PMID- 8156996
TI  - Functional and biochemical association of Hck with the LIF/IL-6 receptor signal
      transducing subunit gp130 in embryonic stem cells.
AB  - The role played by the Src-related tyrosine kinase, Hck, in embryonic stem (ES)
      cell differentiation was investigated by replacing a conserved C-terminally
      located tyrosine with phenylalanine by gene targeting. Targeted ES cells display
      a 7- to 9-fold elevation in constitutive Hck kinase activity and require
      approximately 15 times less leukaemia inhibitory factor (LIF) than parental ES
      cells to maintain their stem cell character in vitro. We also demonstrate a rapid
      and transient increase in Hck tyrosine kinase activity in parental ES cells
      stimulated by LIF and, finally, show that Hck is physically associated with
      gp130, an affinity converter and signal transducing component of the LIF
      receptor. Thus, these results provide biological and biochemical evidence that
      Hck participates in signal transduction from the LIF receptor.

PMID- 8156997
TI  - Neuronal differentiation signals are controlled by nerve growth factor
      receptor/Trk binding sites for SHC and PLC gamma.
AB  - Differentiation and survival of neuronal cell types requires the action of
      neurotrophic polypeptides such as nerve growth factor (NGF). In the central and
      peripheral nervous system and the phaeochromocytoma cell model PC12, NGF exerts
      its effects through the activation of the signalling capacity of Trk, a receptor
      tyrosine kinase (RTK) which upon interaction with NGF becomes phosphorylated on
      tyrosines and thereby acquires the potential to interact with signal-transducing
      proteins such as phospholipase C-gamma (PLC gamma), phosphatidylinositol-3'
      kinase (PI3'-K) and SHC. Mutagenesis of the specific binding sites for these src
      homology 2 (SH2) domain-containing substrates within the Trk cytoplasmic domain
      suggests a non-essential function of PI3'-K and reveals a major role for the
      signal controlled by the SHC binding site at tyrosine 490 and a co-operative
      function of the PLC gamma-mediated pathway for neuronal differentiation of PC12
      cells.

PMID- 8156998
TI  - Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor
      to its signal transduction system (p91).
AB  - Herein we report that interferon-gamma (IFN gamma) induces the rapid and
      reversible tyrosine phosphorylation of the IFN gamma receptor. Using a panel of
      receptor intracellular domain mutants, we show that a membrane-proximal LPKS
      sequence (residues 266-269) is required for ligand-induced tyrosine kinase
      activation and/or kinase-receptor association and biological responsiveness, and
      a functionally critical membrane-distal tyrosine residue (Y440) is a target of
      the activated enzyme. The biological significance of Y440 phosphorylation was
      demonstrated by showing that a receptor-derived nonapeptide corresponding to
      receptor residues 436-444 and containing phosphorylated Y440 bound specifically
      to p91, blocked p91 phosphorylation and inhibited the generation of an active p91
      containing transcription factor complex. In contrast, nonphosphorylated wild
      type, phosphorylated mutant, or phosphorylated irrelevant peptides did not.
      Moreover, the phosphorylated Y440-containing peptide did not interact with a
      related but distinct latent transcription factor (p113) which is activatible by
      IFN alpha but not IFN gamma. These results thus document the specific and
      inducible association of p91 with the phosphorylated IFN gamma receptor and
      thereby elucidate the mechanism by which ligand couples the IFN gamma receptor to
      its signal transduction system.

PMID- 8156999
TI  - Role of phospholipase C in Dictyostelium: formation of inositol 1,4,5
      trisphosphate and normal development in cells lacking phospholipase C activity.
AB  - The micro-organism Dictyostelium uses extracellular cAMP to induce chemotaxis and
      cell differentiation. Signals are transduced via surface receptors, which
      activate G proteins, to effector enzymes. The deduced protein sequence of
      Dictyostelium discoideum phosphatidylinositol-specific phospholipase C (PLC)
      shows strong homology with the mammalian PLC-delta isoforms. To study the role of
      PLC in Dictyostelium, a plc- mutant was constructed by disruption of the PLC
      gene. No basal or stimulated PLC activity could be measured during the whole
      developmental programme of the plc- cells. Loss of PLC activity did not result in
      a visible alteration of growth or development. Further analysis showed that
      developmental gene regulation, cAMP-mediated chemotaxis and activation of
      guanylyl and adenylyl cyclase were normal. Although the cells lack PLC activity,
      inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] was present at only slightly lower
      concentrations compared with control cells. Mass analysis of inositol phosphates
      demonstrated the presence of a broad spectrum of inositol phosphates in
      Dictyostelium, which was unaltered in the plc- mutant. Cell labelling experiments
      with [3H]inositol indicated that [3H]Ins(1,4,5)P3 was formed in a different
      manner in the mutant than in control cells.

PMID- 8157000
TI  - Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.
AB  - Many growth factors whose receptors are protein tyrosine kinases stimulate the
      MAP kinase pathway by activating first the GTP-binding protein Ras and then the
      protein kinase p74raf-1. p74raf-1 phosphorylates and activates MAP kinase kinase
      (MAPKK). To understand the mechanism of activation of MAPKK, we have identified
      Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1. This
      represents the first characterization of sites phosphorylated by this proto
      oncogene product. Ser217 and Ser221 lie in a region of the catalytic domain where
      the activating phosphorylation sites of several other protein kinases are
      located. Among MAPKK family members, this region is the most conserved,
      suggesting that all members of the family are activated by the phosphorylation of
      these sites. A 'kinase-dead' MAPKK1 mutant was phosphorylated at the same
      residues as the wild-type enzyme, establishing that both sites are phosphorylated
      directly by p74raf-1, and not by autophosphorylation. Only the diphosphorylated
      form of MAPKK1 (phosphorylated at both Ser217 and Ser221) was detected, even when
      the stoichiometry of phosphorylation by p74raf-1 was low, indicating that
      phosphorylation of one of these sites is rate limiting, phosphorylation of the
      second then occurring extremely rapidly. Ser217 and Ser221 were both
      phosphorylated in vivo within minutes when PC12 cells were stimulated with nerve
      growth factor. Analysis of MAPKK1 mutants in which either Ser217 or Ser221 were
      changed to glutamic acid, and the finding that inactivation of maximally
      activated MAPKK1 required the dephosphorylation of both serines, shows that
      phosphorylation of either residue is sufficient for maximal activation.

PMID- 8157001
TI  - Pheromones trigger filamentous growth in Ustilago maydis.
AB  - Cell recognition and mating in the smut fungus Ustilago maydis have been proposed
      to involve specific pheromones and pheromone receptors. The respective structural
      genes are located in the a mating type locus that exists in the alleles a1 and
      a2. We demonstrate that binding of pheromone to the receptor can induce a
      morphological switch from yeast-like to filamentous growth in certain strains.
      Using this as biological assay we were able to purify both the a1 and a2
      pheromone. The structure of the secreted pheromones was determined to be 13 amino
      acids for a1 and nine amino acids for a2. Both pheromones are post
      translationally modified by farnesylation and carboxyl methyl esterification of
      the C-terminal cysteine. An unmodified a1 peptide exhibits dramatically reduced
      activity. The pheromone alone is able to induce characteristic conjugation tubes
      in cells of opposite mating type and confers mating competence; even cells of the
      same mating type undergo fusion. We discuss the role of pheromones in initiating
      filamentous growth and pathogenic development.

PMID- 8157002
TI  - The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal
      transduction pathway.
AB  - Mitogen-activated protein (MAP) kinases have been proposed to play a critical
      role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways.
      Although genetic and biochemical studies of RTK pathways in Caenorhabditis
      elegans, Drosophila melanogaster and mammals have revealed remarkable
      similarities, a genetic requirement for MAP kinases in RTK signaling has not been
      established. During retinal development in Drosophila, the sevenless (Sev) RTK is
      required for development of the R7 photoreceptor cell. Components of the signal
      transduction pathway activated by Sev in the R7 precursor include proteins
      encoded by the gap1, drk, Sos, ras1 and raf loci. In this report we present
      evidence that a Drosophila MAP kinase, ERK-A, is encoded by the rolled locus and
      is required downstream of raf in the Sev signal transduction pathway.

PMID- 8157003
TI  - The basis for germline specificity of the hobo transposable element in Drosophila
      melanogaster.
AB  - Previous results suggested that the hobo transposable element is active
      predominantly in the germline of Drosophila. We investigate germline restriction
      of hobo transposition by testing in vitro modified elements for their ability to
      mobilize marked elements in vivo. Although intact hobo elements are germline
      specific, an hsp70 promoter-hobo transposase fusion is active in the soma.
      Analysis of the hsp70-promoted transcript does not provide evidence for splicing.
      Moreover, the hobo promoter confers germline bias to a highly sensitive reporter,
      delta 2-3 P transposase. These results indicate that hobo transposition is
      germline specific due to regulation of transposase production at the level of
      transcription. Thus, although hobo is similar to the P transposable element in
      organization and tissue specificity, it differs in the underlying mechanism
      governing germline specific activity.

PMID- 8157004
TI  - Correction of xeroderma pigmentosum repair defect by basal transcription factor
      BTF2 (TFIIH).
AB  - ERCC3 was initially identified as a gene correcting the nucleotide excision
      repair (NER) defect of xeroderma pigmentosum complementation group B (XP-B). The
      recent finding that its gene product is identical to the p89 subunit of basal
      transcription factor BTF2(TFIIH), opened the possibility that it is not directly
      involved in NER but that it regulates the transcription of one or more NER genes.
      Using an in vivo microinjection repair assay and an in vitro NER system based on
      cell-free extracts we demonstrate that ERCC3 in BTF2 is directly implicated in
      excision repair. Antibody depletion experiments support the idea that the p62
      BTF2 subunit and perhaps the entire transcription factor function in NER.
      Microinjection experiments suggest that exogenous ERCC3 can exchange with ERCC3
      subunits in the complex. Expression of a dominant negative K436-->R ERCC3 mutant,
      expected to have lost all helicase activity, completely abrogates NER and
      transcription and concomitantly induces a dramatic chromatin collapse. These
      findings establish the role of ERCC3 and probably the entire BTF2 complex in
      transcription in vivo which was hitherto only demonstrated in vitro. The results
      strongly suggest that transcription itself is a critical component for
      maintenance of chromatin structure. The remarkable dual role of ERCC3 in NER and
      transcription provides a clue in understanding the complex clinical features of
      some inherited repair syndromes.

PMID- 8157005
TI  - Differential transactivation potential of Oct1 and Oct2 is determined by
      additional B cell-specific activities.
AB  - Cell type-specific transcriptional regulation is generally believed to be
      mediated by sequence-specific transcription factors that are specifically present
      in the corresponding cells. The interaction of the lymphoid-specific Oct2
      transcription factor has been thought to be responsible for the B cell-specific
      activity of octamer-containing promoter and enhancer elements. Here we show that
      physiological concentrations of Oct2 do not suffice to generate octamer-dependent
      promoter activity in non-B cell lines. Furthermore, we have tested the activity
      of octamer-dependent promoter and enhancer elements in B cell lines that lack the
      endogenous Oct2 protein. Our results demonstrate that in these Oct2-deficient B
      cells the ubiquitous endogenous Oct1 protein is able to stimulate octamer
      containing promoters to a level comparable with that of normal Oct2-positive B
      cells. However, reporter constructs bearing the octamer motif in a distal
      enhancer position are not stimulated by the Oct1 protein, but do require the
      presence of Oct2. The B cell-specific octamer-dependent promoter activity
      mediated by Oct1 correlates with the presence of a novel B cell-specific octamer
      binding complex containing the Oct1 protein. From these results we conclude that
      B cells contain two different activities: one that interacts with both Oct1 and
      Oct2 and mediates promoter proximal activity of the octamer motif and a second
      that specifically interacts with Oct2 to confer function from a remote enhancer
      position.

PMID- 8157006
TI  - Translation of encephalomyocarditis virus RNA: parameters influencing the
      selection of the internal initiation site.
AB  - The initiation of encephalomyocarditis virus RNA translation is by internal
      ribosome entry almost exclusively at the 11th AUG codon from the 5'-end, which is
      the central of the three AUG codons in the sequence..[sequence: see text].., and
      is located some 25 nt downstream from an oligopyrimidine tract conserved amongst
      related viruses. As the sequences between the oligopyrimidine tract and AUG-10/11
      are poorly conserved and thus possibly serve only as a spacer, the influence of
      this spacer length on initiation frequency at the three AUG codons was examined
      in vitro and in vivo. Deletion of 11 residues resulted in initiation almost
      exclusively at AUG-12 but at significantly reduced overall efficiency. Insertion
      of eight residues caused a 15-fold increase in initiation frequency at AUG-10 and
      a decrease at AUG-11. Longer insertions reduced overall efficiency without
      changing the initiation site preferences. With the wild-type spacing, complete
      substitution of the oligopyrimidine tract by purines caused a 30-35% decrease in
      initiation efficiency, and partial substitution only a 10-15% decrease. Thus the
      internal initiation mechanism selects the initiation site partly on the basis of
      its distance from upstream elements, of which the oligopyrimidine tract is not
      the most critical, but for reasons not yet understood a preference for AUG-11 is
      superimposed on this selection.

PMID- 8157007
TI  - A conserved secondary structural motif in 23S rRNA defines the site of
      interaction of amicetin, a universal inhibitor of peptide bond formation.
AB  - The binding site and probable site of action have been determined for the
      universal antibiotic amicetin which inhibits peptide bond formation. Evidence
      from in vivo mutants, site-directed mutations and chemical footprinting all
      implicate a highly conserved motif in the secondary structure of the 23S-like
      rRNA close to the central circle of domain V. We infer that this motif lies at,
      or close to, the catalytic site in the peptidyl transfer centre. The binding site
      of amicetin is the first of a group of functionally related hexose-cytosine
      inhibitors to be localized on the ribosome.

PMID- 8157008
TI  - An N-terminal double-arginine motif maintains type II membrane proteins in the
      endoplasmic reticulum.
AB  - Use of alternative initiator methionines in human invariant (Ii) chain mRNA
      results in the synthesis of two polypeptides, Iip33 and Iip31. After synthesis
      both isoforms are inserted into the endoplasmic reticulum (ER) as type II
      membrane proteins. Subsequently, Iip31 is transported out of the ER, guiding MHC
      class II to the endocytic pathway, whereas Iip33, which differs by only a 16
      residue extension at the N-terminus, becomes an ER resident. Mutagenesis of this
      extension showed that multiple arginines close to the N-terminus were responsible
      for ER targeting. The minimal requirements of this targeting motif were found to
      be two arginines (RR) located at positions 2 and 3, 3 and 4 or 4 and 5 or split
      by a residue at positions 2 and 4 or 3 and 5. Transplanting an RR motif onto
      transferrin receptor demonstrated that this motif can target other type II
      membrane proteins to the ER. The characteristics of this RR motif are similar to
      the KK ER targeting motif for type I membrane proteins. Indeed, RR-tagged
      transferrin receptor partially localized to the intermediate compartment,
      suggesting that like the KK motif, the RR motif directs the retrieval of membrane
      proteins to the ER via a retrograde transport pathway.

PMID- 8157009
TI  - The Saccharomyces cerevisiae APS1 gene encodes a homolog of the small subunit of
      the mammalian clathrin AP-1 complex: evidence for functional interaction with
      clathrin at the Golgi complex.
AB  - Clathrin-associated protein (AP) complexes have been implicated in the assembly
      of clathrin coats and the selectivity of clathrin-mediated protein transport
      processes. We have identified a yeast gene, APS1, encoding a homolog of the small
      (referred to herein as sigma) subunits of the mammalian AP-1 complex. Sequence
      comparisons have shown that Aps1p is more similar to the sigma subunit of the
      Golgi-localized mammalian AP-1 complex than Aps2p, which is more related to the
      plasma membrane AP-2 sigma subunit. Like their mammalian counterparts, Aps1p and
      Aps2p are components of distinct, large (> 200 kDa) complexes and a significant
      portion of the Aps proteins co-fractionate with clathrin-coated vesicles during
      gel filtration chromatography. Unexpectedly, even though the evolutionary
      conservation of AP small subunits is substantial (50% identity between mammalian
      and yeast proteins), disruptions of APS1 (aps1 delta) and APS2 (aps2 delta),
      individually or in combination, elicit no detectable mutant phenotypes. These
      data indicate that the Aps proteins are not absolutely required for clathrin
      mediated selective protein transport in cells expressing wild type clathrin.
      However, aps1 delta accentuated the slow growth and alpha-factor pheromone
      maturation defect of cells carrying a temperature-sensitive allele of clathrin
      heavy chain (Chc) (chc1-ts). In contrast, aps1 delta did not influence the
      effects of chc1-ts on vacuolar protein sorting or receptor-mediated endocytosis.
      The aps2 delta mutation resulted in a slight effect on chc1-ts cell growth but
      had no additional effects. The growth defect of cells completely lacking Chc was
      compounded by aps1 delta but not aps2 delta. These results comprise evidence that
      Aps1p is involved in a subset of clathrin functions at the Golgi apparatus. The
      effect of aps1 delta on cells devoid of clathrin function suggests that Aps1p
      also participates in clathrin-independent processes.

PMID- 8157010
TI  - GDI1 encodes a GDP dissociation inhibitor that plays an essential role in the
      yeast secretory pathway.
AB  - GTP binding proteins of the Sec4/Ypt/rab family regulate distinct vesicular
      traffic events in eukaryotic cells. We have cloned GDI1, an essential homolog of
      bovine rab GDI (GDP dissociation inhibitor) from the yeast Saccharomyces
      cerevisiae. Analogous to the bovine protein, purified Gdi1p slows the
      dissociation of GDP from Sec4p and releases the GDP-bound form from yeast
      membranes. Depletion of Gdi1p in vivo leads to loss of the soluble pool of Sec4p
      and inhibition of protein transport at multiple stages of the secretory pathway.
      Complementation analysis indicates that GDI1 is allelic to sec19-1. These results
      establish that Gdi1p plays an essential function in membrane traffic and are
      consistent with a role for Gdi1p in the recycling of proteins of the Sec4/Ypt/rab
      family from their target membranes back to their vesicular pools.

PMID- 8157012
TI  - Mutations that alter the transmembrane signalling pathway in an ATP binding
      cassette (ABC) transporter.
AB  - The maltose transport system of Escherichia coli is a well-characterized member
      of the ATP binding cassette transporter superfamily. Members of this family share
      sequence similarity surrounding two short sequences (the Walker A and B
      sequences) which constitute a nucleotide binding pocket. It is likely that the
      energy from binding and hydrolysis of ATP is used to accomplish the translocation
      of substrate from one location to another. Periplasmic binding protein-dependent
      transport systems, like the maltose transport system of E.coli, possess a water
      soluble ligand binding protein that is essential for transport activity. In
      addition to delivering ligand to the membrane-bound components of the system on
      the external face of the membrane, the interaction of the binding protein with
      the membrane complex initiates a signal that is transmitted to the ATP binding
      subunit on the cytosolic side and stimulates its hydrolytic activity. Mutations
      that alter the membrane complex so that it transports independently of the
      periplasmic binding protein also result in constitutive activation of the ATPase.
      Genetic analysis indicates that, in general, two mutations are required for
      binding protein-independent transport and constitutive ATPase. The mutations
      alter residues that cluster to specific regions within the membrane spanning
      segments of the integral membrane components MalF and MalG. Individually, the
      mutations perturb the ability of MBP to interact productively with the membrane
      complex. Genetic alteration of this signalling pathway suggests that other agents
      might have similar effects. These could be potentially useful for modulating the
      activities of ABC transporters such as P-glycoprotein or CFTR, that are
      implicated in disease.

PMID- 8157013
TI  - Imaging diagnosis and follow-up of infantile hepatic haemangioendothelioma: a
      case report.
AB  - A 4-week-old male infant was admitted to the hospital with acute gastrointestinal
      bleeding and marked coagulopathy secondary to vitamin K malabsorption in the
      presence of cholestasis. Physical examination revealed hepatomegaly and cutaneous
      haemangiomas. Ultrasonography, CT, and MRI demonstrated a multifocal vascular
      process and allowed the diagnosis of infantile hepatic haemangioendothelioma to
      be made without the use of more invasive diagnostic procedures. To avoid high
      output congestive heart failure, the patient was treated with oral
      corticosteroids. After 5 months, rapid involution of the vascular malformations
      ensued. At age 2 years, a magnetic resonance scan confirmed complete resolution
      of the hepatic haemangioendothelioma.

PMID- 8157014
TI  - Anti-immunoglobulin antibodies in children with Schonlein-Henoch syndrome.
      Absence of serum anti-IgA antibodies.
AB  - Circulating immune complexes (CIC) that simultaneously contain IgG and IgA are
      frequently found in IgA nephropathy (IgA-N) and the Schonlein-Henoch syndrome
      (SHS). The presence of anti-immunoglobulin antibodies (IgA anti-IgG and IgG anti
      IgA) was studied by ELISA in the serum of 39 children with SHS and compared to 30
      normal children. The mean level of IgG anti-IgA antibodies (240 +/- 104 u/ml) in
      SHS patients was similar to control values (251 +/- 85 u/ml); the IgA anti-IgG
      antibodies were increased, although only the antibodies against Fc fraction of
      IgG were elevated (185 +/- 71 u/ml in patients vs 127 +/- 24 mu/ml in controls, P
      < 0.0001) without a significant increase of IgA anti-IgGFab antibodies (141 +/-
      54 mu/ml vs. 137 +/- 25 u/ml); 16/39 (41%) of the patients had increased levels
      of IgA anti-IgGFc and 6 of these had also high IgA anti-IgGFab. None of these
      patients had high IgA anti-IgGFab antibodies without simultaneous augmentation of
      IgA anti-IgGFc. Only 3/39 (7.7%) of SHS patients showed high levels of IgG anti
      IgA antibodies. The correlation of IgA anti-IgGFc antibodies with IgA anti-IgGFab
      was very strong (P < 0.0001) but lower with IgG anti-IgA antibodies (P < 0.002).
      In addition, 8/39 children had renal involvement, nevertheless in these patients
      the findings were quite similar, with a non-significant elevation of IgA anti
      IgGF ab antibodies. These results show that the IgA anti-IgG antibodies are more
      frequently increased than IgG anti-IgA antibodies in the SHS; moreover they are
      mainly directed against Fc fraction and are IgA-FR isotype. Our findings suggest
      that the CIC in SHS are likely formed by the reaction of IgA anti-bodies against
      IgG and not vice versa.

PMID- 8157011
TI  - VIP36, a novel component of glycolipid rafts and exocytic carrier vesicles in
      epithelial cells.
AB  - In simple epithelial cells, apical and basolateral proteins and lipids in transit
      to the cell surface are sorted in the trans-Golgi network. We have recently
      isolated detergent-insoluble complexes from Madin-Darby canine kidney cells that
      are enriched in glycosphingolipids, apical cargo and a subset of the proteins of
      the exocytic carrier vesicles. The vesicular proteins are thought to be involved
      in protein sorting and include VIP21-caveolin. The vesicular protein VIP36 (36
      kDa vesicular integral membrane protein) has been purified from a CHAPS-insoluble
      residue and a cDNA encoding VIP36 has been isolated. The N-terminal 31 kDa
      luminal/exoplasmic domain of the encoded protein shows homology to leguminous
      plant lectins. The transiently expressed protein is localized to the Golgi
      apparatus, endosomal and vesicular structures and the plasma membrane, as
      predicted for a protein involved in transport between the Golgi and the cell
      surface. It is diffusely localized on the plasma membrane but can be
      redistributed by antibody modulation into caveolae and clathrin-coated pits. We
      speculate that VIP36 binds to sugar residues of glycosphingolipids and/or
      glycosylphosphatidyl-inositol anchors and might provide a link between the
      extracellular/luminal face of glycolipid rafts and the cytoplasmic protein
      segregation machinery.

PMID- 8157015
TI  - Neurofibromatosis presenting as a severe systemic vasculopathy.
AB  - In a boy with neurofibromatosis type 1 (NF-1), hypertension, septic infection of
      an aneurysm in the deltoid muscle, bowel infarction, multiple arterial aneurysms
      and venous thrombosis occurred within a period of 6 weeks. Histologically,
      vascular neurofibromatosis of the small vessels of the gut was found. This
      unusual occurrence of a multitude of clinical features within a few weeks was
      caused by vascular neurofibromatosis. Awareness of this condition in patients
      with NF-1 may help the paediatrician to avoid unnecessary diagnostic procedures
      and to initiate appropriate symptomatic therapy.

PMID- 8157016
TI  - Hypothalamic growth hormone deficiency in a patient with ring chromosome 18.
AB  - We report on a boy with a ring 18 chromosome associated with hypothalamic growth
      hormone (GH) deficiency. A 12-month trial of GH replacement therapy (0.5
      U/kg/week) resulted in a marked growth acceleration. Our findings emphasise the
      need of evaluating GH secretion in patients with abnormalities of the 18
      chromosome.

PMID- 8157017
TI  - Surfactant replacement therapy: a new risk factor in developing retinopathy of
      prematurity?
AB  - We documented the prevalence of retinopathy of prematurity (ROP) in a group of 46
      infants suffering from a moderate or severe respiratory distress syndrome and
      treated with surfactant replacement therapy (SRT) and 61 controls admitted in the
      year prior to the institution of SRT. Mortality in the treatment group was lower
      than in the control group (15.5% versus 23.8; P = 0.29). The ROP prevalence in
      the treatment group was 47.8% and in the control group 27.9%. To analyse the
      contribution of SRT alone to the prevalence of ROP, multivariate analysis using
      logistic regression technique was used. The odds ratio for SRT was 5.2 with a 95%
      confidence interval of 1.3-20.7, P = 0.02. The prevalence of severe ROP in the
      surfactant treated group was not increased compared to the control group. From
      our data we conclude that SRT increases the risk of developing ROP but is not
      associated with more severe forms of ROP.

PMID- 8157018
TI  - Investigations of the rhythmic function of heart rate, blood pressure and
      temperature in neonates.
AB  - Over a period of 24-30 h in 10 min intervals, the systolic diastolic and mean
      arterial blood pressure, heart rate, rectal and skin temperature were measured
      simultaneously in 17 full-term babies on the 2nd day of life, and in 11 of them
      again at the age of 4 weeks. Each profile was analysed individually by the
      Cosinor method. On the 2nd day of life, a statistically significant circadian
      rhythm could be detected in 12 of the 17 neonates for systolic blood pressure and
      heart rate, in 16 for skin temperature and in all 17 neonates for rectal
      temperature. Summarizing the data of the 17 newborns the circadian rhythm was the
      most frequent component in all functions. A high portion of ultradian rhythms was
      observed as well. With increasing postnatal age, the variance of acrophases
      decreased, particularly for the temperature rhythms. This means that
      synchronization with the environment is beginning. Furthermore, we found an
      increase in the mesor of heart rate and blood pressure and an increase in
      amplitude of temperature.

PMID- 8157019
TI  - Effect of aminophylline on cerebral haemodynamics and oxidative metabolism in
      premature infants.
AB  - The effect of aminophylline on cerebral blood volume and oxidative metabolism in
      newborn infants was investigated with near infrared spectroscopy (NIRS). Thirteen
      mechanically ventilated premature infants who received aminophylline to
      facilitate weaning from the respirator were selected. Gestational age ranged
      between 26 and 34 weeks, postnatal age between 1 and 7 days and birth weight
      between 760 and 2300 g. A bolus of 6 mg aminophylline/kg body weight was infused
      within 2 min. NIRS was performed continuously across the head to monitor changes
      in cerebral blood volume and cytochrome c oxidase. Heart rate, transcutaneous
      carbon dioxide tension (tcpCO2) and arterial haemoglobin oxygen saturation (SO2)
      were recorded simultaneously. The infusion of aminophylline was associated with
      an increase in heart rate (median 12, interquartile range 5-20 beats per min, P =
      0.0004) and a drop in tcpCO2 (median -0.4, interquartile range -0.1 to -0.5 kPa,
      P = 0.015). Oxygen saturation remained stable (+/- 3%). A decrease in cerebral
      blood volume was measured with NIRS in 9/13 patients (median -0.15 ml/100g brain
      tissue, interquartile range +0.08 to -0.28, P = 0.10). Oxidized cytochrome c
      oxidase decreased in 11/13 patients (median -0.27 mumol/l, interquartile range 
      0.19 to -0.44, P = 0.01). Our findings demonstrate an immediate step-response of
      heart rate and tcpCO2 to aminophylline in premature infants. The simultaneous
      reduction of cytochrome c oxidase in the brain cannot be explained as a
      consequence of changes in tcpCO2 or changes in cerebral blood volume. We
      therefore speculate that aminophylline interferes directly with cerebral
      metabolism.

PMID- 8157020
TI  - Subcutaneous recombinant erythropoietin in preterminal renal insufficiency.
AB  - Recombinant human erythropoietin was given to eight children and adolescents with
      stable chronic renal failure in the predialysis state. The hormone was
      administered subcutaneously, twice weekly for 12 weeks, at a starting dose of 50
      U/kg per week. The dosage was adapted every 4th week. Target haemoglobin was 10.5
      11.5 g/dl, and the target haematocrit 32%-35%. Baseline haemoglobin levels of
      8.20 +/- 0.93 g/dl increased to 9.17 +/- 1.10, 10.38 +/- 1.18 and 11.19 +/- 0.84
      g/dl (mean +/- SD) after 4, 8 and 12 weeks respectively. Serum ferritin levels
      decreased progressively despite iron supplementation. No side-effects were
      observed: creatinine clearances remained stable, blood pressure did not increase
      and none of the patients displayed either convulsions or thrombotic features. The
      study shows that subcutaneous recombinant human erythropoietin is both effective
      and safe in anaemic children and adolescents with chronic renal insufficiency.

PMID- 8157021
TI  - Valproate-induced hepatic failure in a case of cytochrome c oxidase deficiency.
AB  - We report a 3 year-old girl with a myoclonic epilepsy. A fatal hepatic failure
      occurred after 3 months of valproate (VPA) therapy. In this patient, a defect of
      cytochrome c oxidase (COX) was demonstrated in her circulating lymphocytes. The
      enzyme was also found to be deficient in post-mortem liver and in cultured skin
      fibroblasts. However, a fully functional respiratory chain was found in muscle.
      VPA administration apparently triggered the hepatic failure, given this patient's
      background of partial COX deficiency.

PMID- 8157022
TI  - A bronchopleurocutaneous fistula caused by an unusual foreign body aspiration
      simulating acute abdomen.
AB  - A 12-year-old boy was admitted to hospital for abdominal pain, vomiting and
      fever. On physical examination he had rales on the lower right hemithorax without
      any respiratory complaints. Chest X-ray revealed a condensation in the right
      lower chest. Abdominal findings were secondary to lobar pneumonia. Treatment of
      pneumonia with antibiotics showed no improvement over 2 days. On bronchoscopy no
      foreign body was seen, but pus was aspirated. Two days later a mass appeared on
      the right hemithorax and fistulized. An organic foreign body, Hordeum murinum,
      with 3-5 ml of pus was observed. Chest X-ray taken at the day of fistulization
      showed no pneumothorax or subcutaneous emphysema. Less than 11 cases of
      pneumocutaneous fistulas secondary to aspiration of grasses have been reported in
      literature. Why an ear of Hordeum murinum can migrate only in a forward direction
      and why a pneumothorax had not developed is discussed.

PMID- 8157023
TI  - Another case of Ritscher-Schinzel-syndrome: craniocerebello-cardiac dysplasia (3C
      syndrome) with associated bilateral colobomata.

PMID- 8157024
TI  - Group B streptococcal endocarditis in infancy with a giant vegetation on the
      pulmonary valve.

PMID- 8157025
TI  - Complications of umbilical vein catheter.

PMID- 8157026
TI  - Stability of frozen muscle used for mitochondrial enzyme assays.

PMID- 8157027
TI  - The type II collagenopathies: a spectrum of chondrodysplasias.
AB  - With the application of molecular techniques the aetiopathogenesis of skeletal
      dysplasias is gradually elucidated. Recent advances show that some bone
      dysplasias result from defects in the biosynthesis of type II (cartilage)
      collagen. Clinical entities caused by mutations in the COL2A1 gene coding for
      type II collagen comprise achondrogenesis II, hypochondrogenesis,
      spondyloepiphyseal dysplasia congenita, Kniest dysplasia, Stickler
      arthroophthalmopathy and mild dominant spondyloarthropathy. The mutations are
      expressed in the heterozygous state, and inheritance of type II collagenopathies
      is autosomal dominant. The wide range of clinical manifestations is not well
      understood but characterization of the basic defect may provide clues to
      establish specific genotype-phenotype correlations.

PMID- 8157028
TI  - Growth hormone and 17 beta-oestradiol treatment of Turner girls--2-year results.
AB  - Girls with Turner syndrome are mainly characterized by growth retardation and
      gonadal insufficiency. In order to evaluate the effect of growth hormone (GH)
      and/or low dose 17 beta-oestradiol (E2) on growth and pubertal development, 39
      Turner girls with a chronological age (CA) of 7.6-18.1 years were divided into
      three groups depending on pretreatment bone age (BA). They were treated with
      either GH 0.1 IE/kg per day (n = 13, BA 7.1-10.2), peroral E2 0.01 mg/kg per day
      (n = 8, BA 8.5-12.7) or both (n = 18, BA 10.5-15.3). In the 2nd year the E2 group
      also received GH, while the E2 dose was reduced 30%. In the 1st year height
      velocity (HV) expressed as standard deviation scores (SDS) increased in all
      groups (mean): from -0.4 to 3.3 (P < 0.01) in the GH group, -0.5 to 2.7 (P <
      0.01) in the E2 group, and -0.8 to 4.6 (P < 0.001) in the GH+E2 group. A possible
      synergistic effect from combination therapy was seen, as HV increase was higher
      in group 3 than groups 1 and 2 (P < 0.05). In the 2nd year HV was unchanged in
      groups 1 and 2, while a clear decrease was seen in the GH+E2 group (P < 0.001).
      In the 1st year BA progression in the E2 group was rapid (1.9 BA/CA year) and
      higher than in the other groups (P < 0.05). In the 2nd year progression slowed
      down--particularly in the E2 group (0.7 BA/CA year, P = 0.07).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8157029
TI  - Hashimoto thyroiditis, distal renal tubular acidosis, pernicious anaemia and
      encephalopathy: a rare combination of auto-immune disorders in a 12-year-old
      girl.
AB  - A case of a 12-year-old girl with a multiple auto-immune disorder is reported.
      She showed Hashimoto thyroiditis which subsequently developed to hashitoxicosis
      and distal renal tubular acidosis at 5 years of age, pernicious anaemia at the
      age of 9 and severe encephalopathy at the age of 12. Laboratory studies revealed
      very high titres of anti-microsomal and anti-thyroglobulin antibodies and
      positive gastric parietal cell antibody. As to the encephalopathy, positive
      oligoclonal IgG bands and high values of IgG index and IgG synthesis ratio in CSF
      were observed with aggravation of her neurological symptoms. High-dose steroid
      therapy was effective toward the encephalopathy. Paediatricians should pay
      careful attention to patients with Hashimoto thyroiditis for association with
      other autoimmune disorders.

PMID- 8157030
TI  - Abbreviated oesophageal pH monitoring in infants.
AB  - The results of 24 h oesophageal pH monitoring, performed in 129 infants aged 6-10
      weeks, were compared to those in the same patients after shorter periods (3, 6, 9
      and 12 h). In the investigated population there was no significant difference
      between the reflux index (percentage of time with a pH < 4.0) after 12 or 24 h.
      Moreover, the correlation coefficient between the reflux index after 12 and 24 h
      was excellent (r 0.95). However, the intra-individual difference in reflux index
      after 12 and 24 h was 5% in 19% of the infants, and even exceeded 10% in more
      than 5% of the infants, making the interpretation of the results unreliable. Even
      in this particular population of infants in whom a 24-h period could be divided
      into almost identical periods (including a feeding and a sleeping period), 24-h
      registrations provided the most reliable results. However, if for some reason the
      investigation had to be interrupted after a minimum of 12 h, the risk for
      erroneous interpretation of the data appeared to be acceptable. The results of
      this study must not be extrapolated to older children.

PMID- 8157031
TI  - Changing causes of septicaemia in paediatric oncology patients: effect of
      imipenem use.
AB  - One hundred and fifty-four episodes of septicaemia occurred in 78 patients on a
      Paediatric Oncology Unit over 2 years. Septicaemias with Gram-positive bacteria
      were more common than with Gram-negative organisms, coagulase-negative
      staphylococci (CNS) being the commonest pathogens. The mortality rate in patients
      with septicaemia was 1.9%. Azlocillin and gentamicin comprised the first-line of
      empirical antibiotic therapy for suspected infection for the first 10 months of
      the study; imipenem with cilastatin, as monotherapy, was used subsequently. More
      isolates of enterococci, and fewer isolates of Enterobacter, were seen after the
      introduction of imipenem. The use of imipenem was associated with an increased
      frequency of resistance to flucloxacillin in CNS. Such strains have been shown to
      contain sub-populations of cells that are resistant to imipenem. A clinical
      response was achieved in 82.9% of septicaemic episodes treated with imipenem,
      compared with 62.7% for azlocillin and gentamicin. However, imipenem as
      monotherapy may not be appropriate in central venous catheter related infections,
      owing to the frequent occurrence of imipenem-resistant organisms, CNS and
      Pseudomonas spp., in this situation.

PMID- 8157032
TI  - Ifosfamide nephrotoxicity in paediatric cancer patients.
AB  - Ifosfamide is an alkylating agent which has been incorporated into frontline
      therapy for a number of malignant paediatric tumours. Recent data appears to
      suggest that tubular dysfunction may result from incorporation of this drug into
      chemotherapy schedules and that toxicity may be dose related. A detailed
      investigation of renal function was performed in a group of patients, ranging in
      age from 8 months to 15.9 years (median 8.6 years) with rhabdomyosarcoma (n = 11)
      and Ewing's sarcoma (n = 9) who were currently receiving (n = 4) or had completed
      ifosfamide (n = 16) therapy a mean of 16 months at the time of study. All but one
      patient demonstrated some degree of renal dysfunction and toxicity did not
      necessarily appear to be dose related. Implications for incorporation of this
      agent into future schedules for childhood sarcomas, which can expect to cure more
      than 60% of such children, must be addressed. The importance of ongoing
      monitoring is emphasised.

PMID- 8157033
TI  - Neonatal allo-immune thrombocytopenia due to fetomaternal HPA-1 incompatibility
      of a homozygous HPA-1a mother and a homozygous HPA-1b father. A case report.
AB  - We report a case of neonatal allo-immune thrombocytopenia due to fetomaternal
      human platelet antigen (HPA)-1 incompatibility. Anit-HPA-1b antibodies were
      detectable in maternal serum. Repeated treatment of the infant with high-dose IgG
      effectively raised platelet counts transiently, but the patient remained
      thrombocytopenic for more than 6 weeks. Serological and DNA analysis revealed
      that the mother was homozygous HPA-1a and the father homozygous HPA-1b.

PMID- 8157034
TI  - Acute intravascular haemolysis following exchange transfusion with G-6-PD
      deficient blood.
AB  - A neonate with hyperbilirubinaemia who developed massive intravascular haemolysis
      following exchange transfusion with glucose-6-phosphate dehydrogenase deficient
      blood is described. It is recommended that in areas endemic for this enzyme
      deficiency the donor blood should be screened before being used for exchange
      transfusion.

PMID- 8157035
TI  - Effect of intravenous dopamine on blood pressure and plasma insulin in
      hypertensive patients.
AB  - Eleven patients with moderate to severe hypertension were pre-treated with oral
      labetalol 800-1200 mg/day for one week, prior to receiving two i.v. infusions of
      dopamine 1-3 micrograms/kg/min each of 30 min each, before and after the i.v.
      bolus injection of metoclopramide 30 mg. There were washout periods before and
      after the metoclopramide administration. Dopamine induced a significant decrease
      of blood pressure from 172/104 to 153/94 mm Hg without altering heart rate, and
      it increased the plasma insulin level from 8.3 to 12.1 microU.ml-1.
      Metoclopramide did not itself affect blood pressure or plasma insulin, but it did
      block the hypotensive response and rise in plasma insulin due to dopamine. We
      conclude that the pharmacological actions of intravenous dopamine on the
      cardiovascular system and on insulin secretion may be mediated by dopaminergic
      receptor stimulation.

PMID- 8157036
TI  - Efficacy and safety of high dose fluvastatin in patients with familial
      hypercholesterolaemia.
AB  - The efficacy and safety of the HMG CoA reductase inhibitor fluvastatin have been
      evaluated in a double blind study in 52 patients with familial
      hypercholesterolaemia. A standard AHA Phase II lipid lowering diet was prescribed
      throughout the study. After 6 weeks of a single blind dosage stabilisation
      period, in which patients received fluvastatin 40 mg qPM, patients were randomly
      allocated to one of two double blind treatment groups: group A (n = 24) received
      fluvastatin 20 mg b.d. for 12 weeks and fluvastatin 20 mg AM + 40 mg PM for an
      additional 12 weeks; Group B (n = 28) received fluvastatin 40 mg qPM during the
      entire study. Safety and tolerability were evaluated by the analysis of
      biochemical and haematological parameters, and ophthalmological and physical
      examinations. Efficacy was analysed by the determination of plasma lipids,
      lipoproteins and apoproteins. Fluvastatin 40 mg/d was associated with up to a
      27.4% decrease in LDL-C and a 9.6% increase in HDL-C concentrations. Increasing
      the dose of fluvastatin from 20 mg b.d. to 60 mg per day in Group A was
      associated with a 7.1% decrease in LDL-C, a 12.1% increase of HDL-C and a 12.8%
      decrease in the LDL-C/HDL-C ratio. In comparison with Group B (40 mg qPM) LDL-C,
      HDL-C and the LDL-C/HDL-C ratio in Group A (60 mg) differed by -8.9%, 6.6% and 
      12%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157037
TI  - Transdermal nicotine in smoking cessation. A meta-analysis.
AB  - A systematic search of the literature was made to identify relevant reports of
      clinical trials of transdermal nicotine, followed by detailed statistical
      analysis of the results to calculate a pooled estimate of the rate of smoking
      cessation. Both a fixed effect and a random effects model were used to calculate
      pooled estimates. The pooled odds ratio (OR) for short-term smoking cessation in
      favour of the transdermal patches was OR = 3.10. Using a random effects model,
      the risk difference (RD) in favour of the transdermal patches was RD = 0.25. The
      corresponding values for long-term cessation were OR = 2.26 and RD = 0.11. Skin
      irritation was a common adverse effect with incidence rates ranging up to about
      70%. Nicotine transdermal patches were effective in promoting smoking cessation
      both in the short-term, with assessments at 3 to 10 weeks, and in the long-term,
      with assessment at 24 to 52 weeks. Long-term abstinence rates in subjects treated
      with nicotine patches for a few weeks remained higher than in subjects treated
      with placebo patches. Adverse effects were usually minor and transient, although
      subjects with a sensitive skin may find the applications intolerable. Further
      studies are required to confirm the value of nicotine patches in promoting
      smoking cessation in the absence of professional medical support and in general
      medical practices in the community.

PMID- 8157038
TI  - Plasma levels of piperacillin and vancomycin used as prophylaxis in liver
      transplant patients.
AB  - The pharmacokinetics of piperacillin and vancomycin used intravenously as
      antibioprophylaxis were measured in the plasma and bile during orthotopic liver
      transplantation. Piperacillin (4 g and then 2 g every 4 h) and vancomycin (1 g
      and then 0.5 g every 6 h) were infused in 10 patients. During vascular clamping
      without venovenous bypass, clearance of both antibiotics decreased in relation to
      renal insufficiency. During the surgical procedure, volume of distribution of
      both drugs increased because of fluid redistribution. The peaks of piperacillin
      after first, second and third administrations were respectively 314, 265 and 210
      mg.l-1, while trough levels were 46.5, 55.2 and 54.5 mg.l-1. The peaks of
      vancomycin were 54.4, 49.6 and 40.9 mg.l-1, while first and second trough levels
      were 9.5 and 12 mg.l-1. These plasma concentrations were quite similar to levels
      reported in healthy subjects despite large blood loss and fluid replacement.
      However, piperacillin trough concentrations (< 64 mg/l) were too low in relation
      to its concentration-dependent antibacterial activity and vancomycin peak
      concentrations (> or = 40 mg/l) were slightly too high in relation to its
      toxicity.

PMID- 8157039
TI  - Central effects of combined bendrofluazide and atenolol administration. A single
      dose study in normal subjects.
AB  - Twelve normal male subjects received single oral doses of atenolol 100 mg (AT),
      bendrofluazide 5 mg (BFZ), combined atenolol 100 mg and bendrofluazide 5 mg
      (AT/BFZ), diazepam 5 mg (Dz), or one of two matching placebos, on each of 6 study
      days. Tests of psychomotor performance [digit symbol substitution (DSST), letter
      cancellation (LCT), continuous attention, choice reaction time (CRT), finger
      tapping, short-term memory, body sway], physiological measurements [critical
      flicker fusion (CFF), two-flash fusion (2FF)] and subjective assessments using
      visual analogue scales (VAS), were performed at 2 and 4 hours post-ingestion. Dz
      (active control) significantly worsened VAS scores at 2 h (+0.68) and reduced
      DSST scores at both 2 h (-15.0) and 4 h (-11.0). AT and BFZ given alone, each
      produced significant worsening of VAS at 2 h [AT +1.0; BFZ +1.38], but had no
      significant effects on performance. In combination however, AT/BFZ at 4 h
      produced significant impairment of DSST scores (-10.4), reduced finger tapping (
      16.5) and increased involuntary rest pauses (+16.5). Despite these effects, no
      change in VAS scores occurred. In summary, we have demonstrated significant
      impairment of psychomotor performance in normal subjects with the AT/BFZ
      combination, which was not evident with the single agents and which occurred in
      the absence of a change in subjective awareness. These central effects may have
      important clinical implications for patients taking combined antihypertensive
      medication.

PMID- 8157040
TI  - Pharmacokinetic model identification and parameter estimation as an ill-posed
      problem.
AB  - For model identification and parameter estimation in the framework of linear
      pharmacokinetics it is most often assumed that the disposition function is a
      finite sum of exponential functions with time constants lambda i and associated
      coefficients Ci. Least-square fitting procedures are used to estimate the
      coefficients Ci and the corresponding discrete locations lambda i on the lambda
      axes. This work presents an alternative approach. It does not assume that the non
      zero coefficients are located at sharply defined values of lambda, but that they
      are represented by a continuous function h(lambda), the spectrum of the
      disposition function. This turns the non-linear least-square problem into a
      linear problem, which is known to be as so-called "ill-posed". Regularization
      methods have been developed in recent years as suitable tools for the treatment
      of such ill-posed problems. Application of Tikhonov regularization to the case of
      the bolus kinetics of propofol in 8 volunteers is demonstrated. In 7 of the 8
      cases a spectrum with 4 to 5 peaks was found, and in one volunteer there were
      only 2 peaks. All spectra with more than 2 peaks showed negative values of
      h(lambda). The method used is described and the results are compared with those
      of conventional compartment analysis.

PMID- 8157041
TI  - The effect of probenecid on paracetamol metabolism and pharmacokinetics.
AB  - The influence of probenecid on the pharmacokinetics of paracetamol was
      investigated in a group of healthy volunteers. Pretreatment with probenecid
      caused a significant decrease in paracetamol clearance (6.23 to 3.42 ml.min-1.kg
      1). The urinary excretion of paracetamol sulphate (243 to 193 mg); and
      paracetamol glucuronide (348 to 74.5 mg) were significantly reduced, whereas that
      of paracetamol was unchanged. Probenecid was shown to be an uncompetitive
      inhibitor of paracetamol glucuronidation in vitro, using rat liver microsomes.

PMID- 8157042
TI  - Pharmacokinetics of intranasal, intramuscular and intravenous glucagon in healthy
      subjects and diabetic patients.
AB  - The pharmacokinetics of intranasal, an intravenous infusion, and intramuscular
      glucagon has been studied in 5 healthy subjects and 11 patients with insulin
      dependent diabetes mellitus. After infusion the elimination half-life was
      significantly longer in diabetics (11.9 vs 6.6 min) and the apparent volume of
      distribution was twice as high in diabetics (0.19 vs 0.37 l.kg-1). The metabolic
      clearance rates were the same in the two groups (18.9 and 21.3 ml.min-1.kg-1 in
      controls and in diabetics) and were about twice those previously reported. After
      1 mg intranasally the Cmax of immunoreactive glucagon (IRG) was similar in
      diabetic and in healthy subjects. Administration of a higher dose (2 mg) to
      diabetic patients produced a higher plasma level, although not proportionately
      so. The AUC after 1 mg was also similar in controls and in diabetics. The
      elimination half-life in both groups was similar to the value found after i.v.
      infusion; it was significantly shorter in controls (5.5 min) than in diabetics
      (13.8 min). In both groups, mean Cmax was significantly lower than after IM
      glucagon, the relative bioavailability of 1 mg intranasally vs IM injection being
      less than 30%. After IM administration, the Cmax and AUC of IRG in controls and
      in diabetic patients, were identical. The apparent elimination half-life was also
      similar in the two groups, and was three- to four-times longer (28.6 and 31.4
      min) than after infusion or intranasal administration, possibly because
      estimation of the t1/2 was affected by slow release of the hormone from the site
      of injection.

PMID- 8157043
TI  - The absolute bioavailability of transnasal butorphanol in patients experiencing
      rhinitis.
AB  - The absolute bioavailability (f) and pharmacokinetics of transnasal butorphanol
      were evaluated in patients experiencing rhinitis. In an open three-way crossover
      study, a single 2-mg dose of butorphanol tartrate was administered by intravenous
      bolus injection (Treatment A), by the transnasal route (Treatment B), or by the
      transnasal route with pretreatment of the vasoconstrictor, oxymetazoline
      (Treatment C). Plasma concentrations of butorphanol were determined using a drug
      specific radioimmunoassay. The pharmacokinetic parameters were derived using the
      noncompartmental methods. Butorphanol was rapidly absorbed after transnasal
      administration. The mean maximum concentrations (Cmax) for the transnasal
      treatment with and without pretreatment of oxymetazoline were 1.61 and 3.01 ng.ml
      1, respectively. The corresponding mean absorption times (MAT) were 1.34 and 0.23
      h. The mean half-life values were 5.95, 6.28, and 5.77 h, for treatments A, B,
      and C, respectively. The resulting mean area under the plasma concentration curve
      (AUC) values were 11.9, 8.6, and 8.07 ng.h.ml-1 for treatments A, B, and C,
      respectively. The estimates for absolute bioavailability (f) of transnasal
      butorphanol were 69% and 72% when administered with and without oxymetazoline,
      respectively. The mean CLT and Vss were 121 l.h-1 and 791 l, respectively, for
      the intravenous treatment. The pretreatment of oxymetazoline significantly
      lowered the Cmax and prolonged the absorption time of butorphanol. Although the
      rate of absorption of transnasal butorphanol was affected by oxymetazoline, the
      absolute bioavailability in rhinitis patients (72%) was similar to that found
      with the pretreatment of oxymetazoline (69%) and those reported in healthy
      volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157044
TI  - Pharmacokinetics of chlorpromazine and key metabolites.
AB  - A study was carried out in 11 healthy young men to investigate the
      pharmacokinetics of chlorpromazine (CPZ) after a bolus intravenous (i.v.) dose
      (10 mg) and three single oral doses (25, 50 and 100 mg), with a washout period of
      two weeks between doses. Plasma levels of CPZ, CPZ N-oxide (CPZNO), CPZ sulfoxide
      (CPZSO) and both free and conjugated 7-hydroxy-CPZ (7-HOCPZ) were measured by
      extraction radioimmunoassays. CPZ exhibited multicompartmental pharmacokinetics
      in most subjects. There was wide between-subject variability in half life (11.05
      h), volume of distribution (1215 l), volume of distribution at steady state (642
      l) and mean residence time (8.88 h), whereas systemic clearance was somewhat less
      variable (76.6 l.h-1). All metabolites were present in measurable concentrations
      in the plasma of 9 of 11 subjects after i.v. CPZ, whereas free 7-HOCPZ was not
      detected in the other 2 individuals. With the exception of CPZNO, the biological
      half lives of the primary metabolites were longer than the half life of CPZ.
      After oral administration, the percentage of CPZ reaching the systemic
      circulation intact (F%) was very low (4-38%) and dose dependent. Moreover, both
      within-subject and between-subject variances were very high. The maximum plasma
      concentration (Cmax) and area under the plasma concentration versus time curve
      extrapolated to infinite time (AUC) showed evidence of nonlinearity, whereas half
      life did not appear to be dose dependent. These data suggest that the high degree
      of variability in the pharmacokinetics of CPZ is a result of extensive first pass
      metabolism rather than variation in half life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157045
TI  - Lack of influence of short-term treatment with propranolol and terbutaline on
      metabolism and energy expenditure of the Na-K pump in human erythrocytes
      evaluated by microcalorimetry.
AB  - A double blind placebo-controlled study was conducted of the effects of oral
      propranolol (beta 1 beta 2-adrenoceptor antagonist) and terbutaline (beta 2
      adrenoceptor agonist) on erythrocyte heat production, measured by direct
      microcalorimetry under static conditions at 37 degrees C and pH 7.4. Propranolol
      80 mg and terbutaline slow-release 7.5 mg were randomly administered twice daily
      for one week to 15 healthy males, using a cross-over design. No thermogenic
      difference was detected. Serum potassium was significantly decreased by
      terbutaline but was only slightly increased by propranolol, but no relationship
      was found between changes in the extra- and intracellular levels. In the placebo
      group, 10% of total cell energy was consumed by the Na-K pump, as assessed by
      ouabain inhibition, and this value was not significantly affected by the
      treatments. Thus, it seems unlikely that there is a clinically relevant influence
      on the Na-K pump in erythrocytes during continuous terbutaline or propranolol
      medication. It is concluded that short term medication with propranolol and
      terbutaline in therapeutic doses has almost no thermal or metabolic effect on
      human erythrocytes. The results indirectly imply that no clinically relevant beta
      adrenoceptor effects are mediated in erythrocytes and this may also be true with
      regard to the 'membrane effect' of propranolol.

PMID- 8157047
TI  - Pharmacodynamic modeling of cortisol suppression from fluocortolone.
AB  - The effect of fluocortolone on cortisol suppression was characterized using a
      'direct suppression pharmacodynamic model'. The model incorporates the
      physiologic circadian secretion of cortisol under normal and treatment
      conditions, together with pharmacokinetic data from single fluocortolone doses of
      20, 50, and 100 mg. A mean IC50 value (fluocortolone plasma concentration at
      which the circadian secretion of cortisol is inhibited by 50%) of 15.5 ng.ml-1
      was found. This analysis shows how use of pharmacodynamic modeling can
      characterize dose-proportionality data to provide an in vivo measure of drug
      potency.

PMID- 8157046
TI  - Protein binding of digitoxin, valproate and phenytoin in sera from diabetics.
AB  - Chronic hyperglycaemia results in glycation of serum albumin and might affect the
      binding of drugs. The aim of the present study was to compare, using an
      equilibrium dialysis method, the protein binding of therapeutic concentrations
      digitoxin, valproate and phenytoin in sera from 70 insulin-dependent diabetics
      and 25 controls. Drug concentrations were measured by fluorescence
      immunopolarisation. Glycated albumin was measured by laser nephelometry after
      affinity chromatography. In sera from diabetics, protein binding of digitoxin
      (88.8 versus 89.9%) was unchanged; the protein binding of valproate (75.2 versus
      80.7%) and phenytoin (67.9 versus 75.3%) was significantly decreased, but with no
      correlation with the concentration of glycated albumin. We conclude that the
      difference in protein binding between diabetic and control sera is due to glucose
      independent modification of albumin in diabetics.

PMID- 8157048
TI  - Flumazenil kinetics in the elderly.
AB  - In an open design, randomised, two-way cross-over study, a single 2 mg i.v. dose
      and a single 30 mg oral dose of flumazenil were each administered to a group of
      healthy young (n = 6) and elderly (n = 12) volunteers (male: female 2/1). Plasma
      samples were collected at intervals and intact drug was assayed. Both the i.v.
      and oral doses of flumazenil were very well tolerated by both age groups and no
      severe or unexpected adverse effects were observed. The main complaints were
      dizziness and headache, mainly after oral dosing, probably due to the higher Cmax
      and AUC following this route of administration. After 2 mg i.v. the disposition
      parameters in the two age groups (elderly/young) were very similar: volume of
      distribution (Vss): 0.88/0.90 l.kg-1; total body clearance (ClPL): 0.86/0.99
      l.min-1; terminal elimination half-life (t1/2 beta): 1.02/0.91 h. After the 30 mg
      oral dose the mean Cmax of 87.6 ng.ml-1 (elderly) and 78.4 ng.ml-1 (young) were
      generally reached within 0.5 to 1 h. In 26% (elderly) and 23% (young), the
      absolute bioavailability of flumazenil was very similar. It is concluded that the
      absorption and disposition parameters of flumazenil were not significantly
      affected by aging.

PMID- 8157049
TI  - Hepatic elimination of ACE inhibitors.

PMID- 8157050
TI  - BW-A522 blocks adenosine A3 receptor-mediated hypotensive responses in the rat.
AB  - The effects of 3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)-1-propylxanthine (I
      ABOPX; BW-A522), which has nanomolar affinity for the recently cloned human and
      sheep adenosine A3 receptor, on the putative A3 receptor mediated hypotensive
      response to N6-2-(4-aminophenyl)ethyl adenosine (APNEA) in the rat have been
      investigated. Following blockade of A1 and A2 receptors with 8-(p
      sulphophenyl)theophylline, BW-A522, 10 and 40 mg/kg i.v., blocked dose
      dependently and surmountable the hypotensive response to APNEA. The results
      provide direct evidence of an A3 receptor in the cardiovascular system of the rat
      which induces hypotension when activated.

PMID- 8157051
TI  - P2 purinoceptors modulating noradrenaline release from sympathetic neurons in
      culture.
AB  - ATP (1 mM) inhibited, whereas 2-methylthio-ATP (30 microM), a P2Y-selective
      purinoceptor agonist, increased electrically evoked release of [3H]noradrenaline
      from chick sympathetic neurons. The P2X-selective purinoceptor agonist alpha,beta
      methylene-ATP (30 microM) had no effect. The ATP-induced inhibition of release as
      well as the facilitation caused by 2-methylthio-ATP was not affected by the
      selective adenosine (P1) receptor antagonist 8-(p-sulfophenyl)-theophylline (8
      PST; 100 microM), but completely prevented by the non-selective P2 antagonist
      suramin (300 microM). The present data reveal a dual regulation of noradrenaline
      release from sympathetic neurons. Facilitation seems to be mediated by a P2Y
      purinoceptor, whereas inhibition is caused by a P2 purinoceptor which needs
      further subtype characterization.

PMID- 8157052
TI  - Effect of E-type prostaglandins on bradykinin-induced plasma extravasation in the
      knee joint of the rat.
AB  - We studied the effect of different E-type prostaglandins on an experimental model
      of inflammation in the rat. Plasma extravasation was induced in the knee joint of
      the rat by continuous perfusion of two potent inflammatory mediators, bradykinin
      (160 nM) or platelet activating factor. Both prostaglandin E1 and prostaglandin
      E2 (0.5-500 ng ml-1), when perfused with bradykinin, produced a similar dose
      dependent enhancement of plasma extravasation. Prostaglandin E2 (0.5-500 ng ml-1)
      also dose dependently enhanced plasma extravasation induced by platelet
      activating factor, while prostaglandin E1 significantly enhanced platelet
      activating factor-induced plasma extravasation only at concentrations above 5 ng
      ml-1. In contrast, co-perfusion of bradykinin or platelet activating factor with
      the prostaglandin E1 analogues, enisoprost and misoprostol (0.5-500 ng ml-1) did
      not enhance plasma extravasation. In fact, misoprostol attenuated plasma
      extravasation induced by bradykinin. These results demonstrate that in the rat
      knee joint, misoprostol and enisoprost have different pharmacological actions
      compared to their parent compound, prostaglandin E1 and to prostaglandin E2.

PMID- 8157054
TI  - Multiple [3H]DTG binding sites in guinea pig cerebellum: evidence for the
      presence of non-specific binding.
AB  - The characteristics of the low affinity component of 1,3-di(2-[5
      3H]tolyl)guanidine binding to the guinea pig cerebellum were investigated.
      Saturation binding assays where sigma 1 receptors were masked with dextrallorphan
      indicated that 1,3-di(2-[5-3H]tolyl)guanidine bound to cerebellar membranes in a
      fashion best described by a 1 site+non-specific binding model with a low density
      of specific binding sites (Bmax approximately 200 fmol/mg protein). Boiling the
      cerebellar membranes before addition to the saturation assay had no effect on the
      density of 1,3-di(2-[5-3H]tolyl)guanidine binding. In contrast, both the Kd and
      Bmax for 1,3-di(2-[5-3H]tolyl)guanidine binding to liver membranes was
      significantly reduced by boiling, as was the density of [3H](+)-pentazocine
      binding to cerebellum and liver. Thus, a substantial component of 1,3-di(2-[5
      3H]tolyl)guanidine binding in the guinea pig cerebellum is to non-specific,
      proteinaceous binding sites with some of the pharmacological characteristics of
      the sigma 2 binding site.

PMID- 8157053
TI  - Interaction of [D-Pen2,D-Pen5]enkephalin and [D-Ala2,Glu4]deltorphin with delta
      opioid receptor subtypes in vivo.
AB  - The interaction of [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2,Glu4]deltorphin
      with delta-opioid receptor subtypes was investigated. Pretreatment of mice with
      the delta 1-opioid receptor antagonist, [D-Ala2,Leu5,Cys6]enkephalin (DALCE),
      produced a virtually complete antagonism of the antinociceptive actions of DPDPE,
      but had no effect on those of [D-Ala2,Glu4]deltorphin. In DALCE pretreated mice
      (i.e., delta 1-opioid receptors blocked), DPDPE was able to significantly
      antagonize the antinociceptive effects of [D-Ala2,Glu4]deltorphin. Pretreatment
      of mice with the delta 2-opioid receptor antagonist, naltrindole-5'
      isothiocyanate (5'-NTII) produced a virtually complete antagonism of the
      antinociceptive effects of [D-Ala2,Glu4]deltorphin, but had no effect on the
      antinociception produced by DPDPE. In 5'-NTII pretreated mice (i.e., delta 2
      opioid receptors blocked), [D-Ala2,Glu4]deltorphin had no effect on the
      antinociception produced by DPDPE. These data suggest that [D
      Ala2,Glu4]deltorphin is highly selective for the delta 2-opioid receptor in vivo,
      and that neither agonist nor antagonist actions can be demonstrated at delta 1
      opioid receptors for this peptide. In contrast, under appropriate conditions,
      DPDPE can be shown to interact with both delta 1- and delta 2-opioid receptor
      subtypes; DPDPE may have limited efficacy (i.e., is a partial agonist) at the
      delta 2-opioid receptor.

PMID- 8157055
TI  - Human recombinant phospholipase A2 inhibits platelet aggregation in vitro and in
      vivo in rat and guinea pig.
AB  - Platelets contain a phospholipase A2 in their granules which can be released in
      response to various activating stimuli in vitro as well as in vivo. Human
      recombinant phospholipase A2 (1-10 micrograms/ml) had no direct effect on
      platelet aggregation in vitro using rabbit platelet rich plasma. In contrast
      human recombinant phospholipase A2 (1-20 micrograms/ml) was able to inhibit
      aggregation of washed rabbit platelet in vitro induced by collagen (0.250-2.0
      micrograms/ml). When rabbit platelet rich plasma was recalcified with CaCl2 1 M
      in the presence of the thrombin inhibitor hirulog (10 micrograms/ml), human
      recombinant phospholipase A2 (10-40 micrograms/ml) was able to inhibit platelet
      aggregation. The anti-aggregatory effect was removed by incubation of platelet
      rich plasma with a monoclonal anti-human recombinant phospholipase A2 antibody.
      Human recombinant phospholipase A2 (1-10 micrograms) inhibited 111In-labelled
      platelet accumulation within the thoracic region of rats and guinea pigs induced
      by i.v. administration of submaximal doses of collagen or adenosine diphosphate.
      Phospholipase A2 (1-20 micrograms/ml) from Naja mocambique mocambique snake venom
      had no direct effect on platelet aggregation in vitro. However, Naja
      phospholipase A2 administered i.v. to rats or guinea pigs was able to induce a
      dose related accumulation of 111In-labelled platelet within the thoracic region.
      The inhibitory effect of exogenously added human recombinant phospholipase A2 on
      platelet aggregation in vivo suggests a possible pathophysiological role for the
      extracellular form of phospholipase A2 but this property is not a feature of all
      phospholipase A2 preparations.

PMID- 8157056
TI  - Intravenous NBQX inhibits spontaneously occurring sympathetic nerve activity and
      reduces blood pressure in cats.
AB  - 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) has been
      demonstrated to be a specific and competitive non-N-methyl-D-aspartate (non-NMDA)
      glutamate receptor antagonist. Our previous data obtained with the NMDA receptor
      antagonist MK-801 indicate that blockade of the NMDA receptor affects blood
      pressure. The purpose of this study was to determine whether the same is true
      with blockade of the non-NMDA receptor. For this purpose we administered three
      doses of NBQX (1, 3 and 10 mg/kg i.v.) to anesthetized, artificially ventilated
      and paralyzed cats while monitoring spontaneously occurring cardiac sympathetic
      nerve activity, arterial blood pressure and heart rate. The 1 mg/kg dose of NBQX
      i.v. reduced both sympathetic nerve activity (-29 +/- 7%, P < 0.05, n = 4) and
      blood pressure (-27 +/- 5 mmHg, P < 0.05). Injection of 3 mg/kg NBQX produced a
      greater decrease in sympathetic nerve activity (-78 +/- 11%, P < 0.01, n = 8) and
      mean arterial pressure (-47 +/- 5 mmHg) and also reduced heart rate (-11 +/- 2
      beats/min, P < 0.01). The depressant effects of NBQX on sympathetic nerve
      activity, blood pressure and heart rate were similar regardless of whether
      activity was recorded from pre- or postganglionic cardiac nerves, or from animals
      subjected to baroreceptor denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157057
TI  - Pharmacological characterization of 5-HT receptors in parasympathetic innervation
      of rat heart.
AB  - A study was made of the effects of 5-hydroxytryptamine (5-HT) on bradycardia
      induced in vivo by electrical stimulation of the vagus nerves in pithed rats
      pretreated with atenolol. 5-HT significantly decreased vagally induced, but not
      acetylcholine-induced, bradycardia. The first effect was blocked by methiothepin,
      ketanserin or methiothepin with ketanserin. When 5-HT1 and 5-HT2 receptors were
      blocked, 5-HT produced an increase in vagally induced bradycardia. Both the
      inhibition and the potentiation were blocked by simultaneous pretreatment with
      methiothepin, ketanserin and MDL-72222. The 5-HT2 receptor agonist m-CPP (1-(3
      chlorophenyl) piperazine dihydrochloride) caused an inhibition of vagally induced
      bradycardia whereas the 5-HT3 receptor agonist m-CPBG (1-(m
      chlorophenyl)biguanide hydrochloride) produced a significant increase. The data
      suggest the presence of presynaptic and/or ganglionic 5-HT2 receptors in
      parasympathetic innervation of the rat heart, stimulation of which inhibits the
      release of acetylcholine. The presence of 5-HT3 receptors is also suggested,
      stimulation of which induces the release of acetylcholine.

PMID- 8157058
TI  - Cellular Ca2+ loading and inotropic effects of doxorubicin in atrial muscle
      preparations isolated from rat or guinea-pig hearts.
AB  - The inotropic effects of doxorubicin were examined under conditions that alter
      the Ca2+ loading of myocardial cells. Atrial muscle preparations isolated from
      rat or guinea-pig hearts were used. Cellular Ca2+ loading was altered by changing
      the temperature, extracellular Ca2+ concentrations or the frequency of electrical
      stimulation. In guinea-pig heart muscle preparations stimulated at 2 Hz at 30
      degrees C in the presence of 1.2 mM CaCl2, 30 microM doxorubicin caused biphasic
      (early and late phase) positive inotropic effects. A higher concentration (200
      microM) of doxorubicin caused a transient positive inotropic effect followed by a
      gradual decrease in developed tension. An increase in CaCl2 concentration from
      1.2 to 2.4 mM decreased the positive inotropic effect of 30 microM doxorubicin
      and changed the inotropic effect of 200 microM doxorubicin from positive to
      negative after a transient increase in developed tension. At 0.5-Hz stimulation
      or 36 degrees C incubation, 30 or 200 microM doxorubicin produced remarkable late
      phase positive inotropic effects. In rat heart muscle preparations, the patterns
      of the inotropic effects of doxorubicin were similar to those observed with
      guinea-pig hearts; however, the negative inotropic effect observed at 200 microM
      doxorubicin was greater. These results indicate that the early and the late phase
      positive inotropic effects of doxorubicin have different mechanisms. The pattern
      of inotropic effects of doxorubicin is affected by conditions that alter cellular
      Ca2+ loading or the concentration of doxorubicin.

PMID- 8157059
TI  - The effect of non-steroidal anti-inflammatory drugs on the electrical properties
      of cultured dog tracheal epithelial cells.
AB  - The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the electrical
      properties of primary cultures of dog tracheal epithelium has been studied. The
      cells used were grown with an air interface in a serum-free medium on membranes
      coated with human placental collagen. When mounted in Ussing chambers at 37
      degrees C, mean values for the baseline short circuit current (Isc) and the
      transepithelial resistance of 65 tissue specimens from 18 dogs were 24.0 +/- 3.2
      microA/cm2 and 458 +/- 128 omega.cm2, respectively. These tissues had been
      pretreated with amiloride to abolish active Na+ absorption. Under these
      conditions, the Isc value serves as a measure of active Cl- secretion. The
      results of this study revealed that the Isc across a cultured monolayer of
      trachea was attenuated by the tested NSAIDs, indomethacin, fulfenamic acid,
      mefenamic acid, aspirin, and acetaminophen, with Ki's that ranged from 6.0 x 10(
      5) to 2.51 x 10(-3) M. Salicylic acid had no effect on baseline Isc. The Isc
      sensitivity sequence to the Cl- channel inhibitors tested was: fulfenamic acid >>
      indomethacin > mefenamic acid >> aspirin > acetaminophen > salicylic acid. The
      NSAIDs also significantly inhibited both the transient, Ca(2+)-dependent and the
      sustained, cAMP-dependent increases in Isc elicited by isoproterenol. Thus, the
      tested NSAIDs appeared to have an effect on the electrical properties of the
      cells. A similar effect of NSAIDs on ion transport across the human airway
      epithelium may help to reduce airway fluid secretion.

PMID- 8157060
TI  - Dequalinium, a selective blocker of the slow afterhyperpolarization in rat
      sympathetic neurones in culture.
AB  - The actions of dequalinium have been investigated in cultured rat sympathetic
      neurones. It produced a rapid and reversible inhibition of the slow apamin
      sensitive component of the afterhyperpolarization (AHP) which follows a single
      action potential in these cells. The IC50 for this effect was 1.1 microM and in
      voltage clamp experiments, 1 microM dequalinium produced 45% inhibition of the
      underlying current IAHP. When the small conductance Ca(2+)-activated K+ channels
      were blocked by 20 nM apamin the slow component of the AHP was abolished, and
      dequalinium (10 microM) produced no further change in the residual AHP.
      Dequalinium (10 microM) had no effect on the voltage-activated Ca2+ current in
      these cells, suggesting that the inhibition of the AHP was the result of a direct
      interaction with the K+ channels. The A-current as well as a composite current
      made up of IK and IC were all unaffected by 10 microM dequalinium. However, at
      this concentration it did produce 18% inhibition of the M-current. These results
      show dequalinium to be a potent and selective non-peptide blocker of the apamin
      sensitive small conductance Ca(2+)-activated K+ channel in rat sympathetic
      neurones.

PMID- 8157061
TI  - Differential effects of indomethacin and dexamethasone on cytokine production in
      carrageenin-induced rat pleurisy.
AB  - The effect of anti-inflammatory drugs on cytokine production at local
      inflammatory sites was investigated in a carrageenin-induced rat pleurisy model.
      Exudate volume and leukocyte number in the pleural cavity at 3 h after the
      carrageenin injection were significantly reduced by the pretreatment with
      indomethacin or dexamethasone. Both drugs also reduced the prostaglandin E2 level
      in the exudate. However, production of tumor necrosis factor (TNF) and
      interleukin-1 in the pleural exudate was significantly enhanced by the
      pretreatment with indomethacin, whereas the interleukin-6 level was reduced.
      Pretreatment with dexamethasone markedly suppressed all these cytokine levels.
      When resident pleural cells were stimulated with lipopolysaccharide in vitro, the
      presence of exogenous prostaglandin E2 reduced the production of TNF and
      interleukin-1, while it increased that of interleukin-6 in a dose-dependent
      manner. These results suggest that prostaglandin E2 could be a regulating factor
      involved in cytokine production at the inflammatory site. Dexamethasone may
      express a direct suppressive action on cytokine production rather than an
      indirect regulatory action through prostaglandin E2 level.

PMID- 8157062
TI  - The calcium sensitizer EMD 53998 antagonizes phosphate-induced increases in
      energy cost of isometric tension in cardiac skinned fibres.
AB  - We have investigated whether a Ca(2+)-sensitizing substance, the thiadiazinone
      derivative EMD 53998, can alter the ratio of ATPase activity to force, i.e. the
      tension cost in skinned fibres of swine cardiac trabecula in which the tension
      cost was increased by inorganic phosphate. In the presence of 10 mM inorganic
      phosphate (Pi) and thapsigargin 20 microM, EMD 53998 reduced the energy cost of
      isometric tension over the entire range of activating Ca2+ concentrations,
      resulting in a consistent change in slope (approximately 20% decrease) of the
      ATPase/force relation. We confirmed that in the absence of added phosphate and at
      maximal Ca2+ activation EMD 53998 had little if any effect on tension cost. We
      had previously reported that the effects of EMD 53998 and Pi on calcium
      sensitivity and maximum isometric tension are mutually antagonistic and our new
      energy data now support the proposal that EMD 53998 functionally antagonizes the
      effects of Pi on crossbridges. The decrease in the slope of the relation between
      ATPase and force caused by EMD 53998 may be interpreted to reflect either a
      decrease in the rate of 'detachment' (g(app)) of crossbridges or an increase in
      average force per crossbridge, as predicted by classical crossbridge models.
      Since the Pi release step of the crossbridge cycle is associated with the rate of
      'attachment' (f(app)) rather than g(app), we conclude that the decrease in
      tension cost with EMD 53998 most likely reflects an increased force per
      crossbridge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157063
TI  - Age-dependent differences in the rate of recovery of striatal dopamine D1 and D2
      receptors after inactivation with EEDQ.
AB  - Recovery of striatal dopamine D1 and D2 binding sites in 10-, 16-, and 39-day-old
      rats was measured 1, 2, 4, and 8 days after irreversible antagonism with N
      ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Ontogenetic and EEDQ-induced
      changes in D1 and D2 binding sites were determined by Scatchard analyses using
      six concentrations of either [3H]SCH 23390 or [3H]spiperone. Twenty-four hours
      after EEDQ (7.5 mg/kg) treatment, a significant depletion of both dopamine D1 and
      D2 receptors was found for all age groups; however, the magnitude of the
      depletion was greater in 39-day-old rats than in the two preweanling age groups.
      Both 16- and 39-day-old rats showed significant recovery of dopamine D1 and D2
      receptors by the eighth day after EEDQ treatment, but the 16-day-old rats showed
      a faster recovery of dopamine D1 receptors than did the 39-day-olds.
      Unexpectedly, 10-day-old rats did not show any evidence of receptor recovery, as
      the percent control values for these animals did not change across the 8-day
      recovery period. Pretreatment with the dopamine D1 receptor antagonist SCH 23390
      and the dopamine D2 receptor antagonist sulpiride was sufficient to protect
      dopamine D1 and D2 receptors from EEDQ-induced inactivation. Protein values and
      receptor affinity (pKd values) were not affected by EEDQ treatment at any of the
      ages tested. Therefore, these results indicate that the rate of dopamine receptor
      repopulation varies across ontogeny, with 10-day-old rats exhibiting slower
      recovery than older rat pups or postweanling rats.

PMID- 8157064
TI  - Polyamine potentiation and inhibition of NMDA-mediated increases of intracellular
      free Ca2+ in cultured chick cortical neurons.
AB  - Polyamine potentiation and inhibition of N-methyl-D-aspartate (NMDA) receptor
      mediated Ca2+ changes was studied in cultured chick cortical neurons. Spermidine
      and spermine potentiated the effect of saturating concentrations of NMDA and
      glycine. No effect of spermidine or spermine was observed in the absence of NMDA
      or in the presence of either kainate or quisqualate. Similarly, antagonism of the
      NMDA receptor complex with dizocilpine (an open channel blocker), or with
      competitive antagonists to the NMDA or glycine binding sites greatly attenuated
      or completely abolished the combined effects of polyamines plus NMDA and glycine.
      N-Acetylspermine and N-acetylspermidine, in the presence or absence of NMDA and
      glycine, were without effect. These data strongly suggest that spermidine and
      spermine are potent and selective agonists at the polyamine binding site.
      Putrescine and diethylenetriamine were ineffective as antagonists of NMDA
      mediated intracellular free Ca2+ increases in the presence or absence of added
      spermine or spermidine. Arcaine and 1,10-diaminodecane, however, antagonized NMDA
      mediated intracellular free Ca2+ increases in the presence and absence of
      spermine and spermidine, and therefore appear to act either as inverse agonists
      at the polyamine binding site or as open channel blockers of the NMDA receptor.

PMID- 8157065
TI  - Indapamide alters the cyclic AMP signal transduction pathway in cardiomyocytes in
      culture.
AB  - The cellular mechanism of action on the heart of the antihypertensive/diuretic
      agent indapamide is uncertain. Because of the importance of cAMP in signal
      transduction in the heart, the present study was designed to examine the
      hypothesis that indapamide interacts with the cAMP signal transduction pathway.
      Ventricular cardiomyocytes were isolated from 7-day-old chick embryo hearts and
      were maintained in culture. Indapamide did not alter basal and isoproterenol
      stimulated cAMP levels in cardiomyocytes. However, indapamide pretreatment
      markedly accentuated forskolin-stimulated cAMP production. It also accentuated
      cholera toxin-induced increases in cAMP. Thus these data indicate that indapamide
      has an effect directly on the heart as manifested by its action on the
      ventricular cardiomyocytes. An effect of indapamide on cAMP generation by cholera
      toxin and forskolin suggests both a direct effect on adenylyl cyclase as well as
      an action through Gs. These findings may provide a cellular mechanism of action
      explaining indapamide's effect on the heart.

PMID- 8157066
TI  - cAMP analogues and cholera toxin stimulate the accumulation of nitrite in rat
      peritoneal macrophage cultures.
AB  - Rat peritoneal macrophages incubated with the two stable analogues of cAMP,
      dibutyryl-cAMP and 8-bromo-cAMP, as well as with cholera toxin, released nitrite
      in a dose-dependent manner. Cholera toxin and dibutyryl-cAMP enhanced nitrite
      release induced by bacterial lipopolysaccharide. The stimulatory effects of all
      these substances were inhibited by the nitric oxide synthase inhibitor NG
      monomethyl-L-arginine, dexamethasone and the protein synthesis inhibitor,
      cycloheximide. Our data indicate that the activation of cAMP-dependent pathway(s)
      can induce nitric oxide synthesis in rat peritoneal macrophages even in the
      absence of immunological stimuli, such as exogenous cytokines or
      lipopolysaccharide, although the exact mechanism of this phenomenon remains to be
      established.

PMID- 8157067
TI  - [3H](+)-pentazocine binding to rat brain sigma 1 receptors.
AB  - [3H](+)-Pentazocine binding has been characterized in the rat brain. It binds to
      a single population of binding sites with affinity of about 7 nM and density of
      280 fmol/mg protein. [3H](+)-Pentazocine binding is not enriched in the crude
      synaptic membrane, being about 1/6 of what we found in the crude membrane
      preparation. The binding, like that for other sigma ligands, was enriched in the
      microsomal and nuclear fractions. The inhibition by haloperidol, proadifen and d
      fenfluramine was the same in the crude synaptic membrane, nuclear and microsomal
      fractions, suggesting that [3H](+)-pentazocine binds to a homogeneous protein in
      the different subcellular fractions. Our pharmacological characterization using
      45 different drugs suggests that the [3H](+)-pentazocine binding site in rat
      brain differs from other sigma ligands, like N-propyl-3-(3
      hydroxyphenyl)piperidine ([3H](+)-3PPP), N,N'-di(o-tolyl)guanidine ([3H]DTG) and
      (+)-N-allylnormetazocine ([3H](+)-SKF10,047). [3H](+)-Pentazocine binding in rat
      brain is inhibited by sigma compounds and some cytochrome P450 ligands, like
      proadifen and 1-[2-[bis(4-fluoro-phenyl) methoxy]ethyl]-4-[3-phenylpropyl]
      piperazine (GBR 12909), although with considerably lower potency than reported
      for other sigma ligands. Other inhibitors are some serotonin uptake blockers or
      their metabolites and phenylalkylamines.

PMID- 8157068
TI  - Chronic morphine induces tolerance and desensitization of mu-opioid receptor but
      not down-regulation in rabbit.
AB  - Tolerance to chronic morphine treatment was studied in adult rabbits and
      modifications in the number and the state of coupling of the mu-opioid receptors
      were investigated in the cerebellum. Tolerance was induced by the subcutaneous
      injection of progressively increasing doses of morphine (5-100 mg/kg/injection)
      over 6 days and its occurrence was controlled by a nociceptive test: electrical
      stimulation of the dental pulp. At the end of the treatment, the rabbits were
      tolerant to the analgesic effects of morphine and the tolerance phenomenon
      correlated well with a significant decrease in the adenylate cyclase inhibition
      (approximately 60%). The functional uncoupling between the enzyme and the mu
      opioid receptor was accompanied neither by a decrease in the number of high
      affinity receptors measured by equilibrium binding techniques (Kd = 0.19 +/- 0.03
      in control vs. 0.11 +/- 0.04 nM in tolerant animals; Bmax = 322 +/- 62 vs. 362 +/
      58 fmol/mg of protein), nor by a modification of the physical coupling between
      the receptor and its G-protein. It can be concluded that desensitization, under
      our experimental conditions, can be clearly distinguished from down-regulation.

PMID- 8157069
TI  - Impaired expression of Gs alpha protein mRNA in rat ventricular myocardium with
      aging.
AB  - We have recently reported that the responsiveness of adrenoceptors is decreased
      with aging in rat ventricular myocardium. Thus, the current study determined
      aging-dependent changes in: (a) characteristics of myocardial G proteins as
      determined by Western blot analysis; (b) steady-state levels of G protein mRNA as
      determined by Northern blot analysis; and (c) the intropic response to
      isoproterenol, a beta-adrenoceptor agonist. Cardiac preparations were isolated
      from male Wistar rats of 6 (adult) and 24 (old) months old. Compared with adults,
      aging decreased the combined level of the three Gs alpha subunits (45, 47 and 52
      kDa) by a total of 23% in ventricular membrane preparations. In contrast, levels
      of Gi alpha (40/41 kDa), Gq alpha (42 kDa), Go alpha (39 kDa) and G common beta
      (35/36 kDa) immunoreactivity were not affected by aging in the same membrane
      preparations. In ventricular myocardium, steady-state levels of Gs alpha mRNA
      (1.9 kb) decreased by 20-28% between 6 and 24 months of age with no change in Gi
      alpha mRNA (2.4 kb). An aging-associated decline in beta-adrenergic stimulation
      was observed in the maximum positive inotropic effect elicited by isoproterenol
      in the presence of prazosin in left papillary muscles, with no change in ED50
      values. These results suggest that age-related changes in cardiac excitation and
      contraction coupling following beta-adrenoceptor stimulation are mediated, at
      least in part, by Gs alpha protein dysfunction.

PMID- 8157070
TI  - Mechanism of delta-opioid receptor selection by the address domain of
      dermenkephalin.
AB  - Dermenkephalin (Tyr-D-Met-Phe-His-Leu-Met-AspNH2) is a highly potent and
      selective delta-opioid peptide isolated from frog skin. It was recently
      recognized that the C-terminus His4-Leu5-Met6-Asp7NH2 of dermenkephalin was
      responsible for the addressing of the peptide towards the delta-opioid receptor.
      In order to investigate the role played by residues 4, 5 and 6 in this 'delta
      address', we synthesized and evaluated 20 new analogues for their ability to
      displace tritiated ligands from mu- and delta-opioid sites. Results showed that
      position 4 of dermenkephalin contributes to delta selectivity independently of
      delta-opioid receptor binding by preventing a high affinity mu binding. Position
      5 requires a hydrophobic side chain to enhance delta affinity. A high delta
      affinity was obtained with any amino acids introduced in position 6 suggesting
      that residue 6 serves as a neutral spacer. Thus, the main features responsible
      for the high delta-opioid selectivity of dermenkephalin are electrostatic
      repulsions with the mu-opioid receptor, additional hydrophobic interactions with
      the delta-opioid receptor and folding of the C-terminal domain.

PMID- 8157071
TI  - Properties of a recombinant kainate receptor expressed in baculovirus-infected
      insect cells.
AB  - GluR6 is a glutamate receptor of the kainate subtype that is expressed in the
      mammalian central nervous system. The cDNA coding for the rat brain receptor was
      subcloned into a baculovirus expression vector and the purified recombinant virus
      was used to infect Spodoptera frugiperda (Sf9) insect cells. The pharmacological
      profile and the status of several post-translational modifications of the GluR6
      protein were analyzed. Saturation analyses of [3H]kainic acid binding
      demonstrated that GluR6 expressed in Sf9 cell membranes bound [3H]kainic acid at
      a single high affinity site with a dissociation constant of 12 nM. Competition
      studies indicated the inhibitory potencies of various excitatory amino acids,
      including the potent neurotoxin domoic acid, were comparable to those observed in
      mammalian brain tissue. Immunoblots of infected Sf9 cell membranes using an anti
      GluR6 antibody revealed two immunoreactive bands. Enzymatic deglycosylation
      indicated that the higher molecular weight form corresponded to the glycosylated
      receptor whereas the lower molecular weight form corresponded to the
      unglycosylated protein. The phosphorylation of GluR6 by cyclic AMP-dependent and
      cyclic GMP-dependent protein kinase was examined in partially purified
      preparations of the receptor. GluR6 was phosphorylated by cyclic AMP but not by
      cyclic GMP-dependent protein kinase in vitro. These results indicate that GluR6
      expressed in Sf9 cells has similar pharmacological properties and is processed
      post-translationally in a manner similar to GluR6 expressed in mammalian cells
      and tissues. The ease of production and the high levels of expression in
      baculovirus-infected insect cells relative to other expression systems should
      facilitate further biochemical and pharmacological characterization of this
      receptor.

PMID- 8157072
TI  - Antagonism of presynaptically mediated depressant responses and cyclic AMP
      coupled metabotropic glutamate receptors.
AB  - The depression of monosynaptic excitation of neonatal rat motoneurones by (1S,3S)
      and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) and by L-2-amino-4
      phosphonobutyrate (L-AP4), which is probably presynaptically mediated, is
      antagonized by (+/-)- and (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). The
      same phenylglycine derivatives also antagonize the depression of forskolin
      stimulated cyclic AMP synthesis effected by the two ACPD stereoisomers and by L
      AP4. These results support previous suggestions that presynaptic depression is
      mediated by metabotropic glutamate receptors negatively coupled to adenylyl
      cyclase activity. MCPG is the first antagonist to be reported for these
      receptors.

PMID- 8157073
TI  - Glutamatergic regulation of cannabinoid receptor gene expression in the caudate
      putamen.
AB  - Glutamatergic regulation of delta-9-tetrahydrocannabinol (THC) receptor gene
      expression in the adult rat dorsal striatum following a 2 week unilateral
      cerebral decortication or pharmacological treatment with MK-801 was investigated
      by quantitative in situ hybridization. The caudate-putamen on the side of the
      cerebral decortication contains about 30% significantly lower mRNA levels than
      the control. In addition, we observed a 52% significant decrease in THC receptor
      mRNA levels in intact dorsal striatum after treatment with MK-801. Together these
      results suggest that in vivo, through the NMDA receptor subtype, glutamate up
      regulates THC receptor gene expression in the rat caudate-putamen.

PMID- 8157074
TI  - Interaction of guanidinium compounds and K+ channel modulators with imidazoline
      binding sites in rabbit kidney.
AB  - Several guanidinium compounds were tested for their ability to inhibit the
      binding of [3H]idazoxan to the I2 subtype of the imidazoline site on rabbit
      kidney basolateral membranes. Phenformin, a biguanide, was the most potent with
      an IC50 of 50 +/- 3 microM. Various K+ channel modulators were also evaluated for
      inhibition of [3H]idazoxan binding. 1,2,3,4-Tetrahydro-9-aminoacridine and 4
      aminopyridine (IC50 values of 38 +/- 5 microM and 43 +/- 3 microM, respectively)
      were the most effective of the K+ channel blockers tested. Pinacidil, an ATP
      sensitive K+ channel opener, inhibited radioligand binding with an IC50 of 100 +/
      10 microM. The results indicate that I2 sites are selective in their interaction
      with guanidinium derivatives and K+ channel modulators.

PMID- 8157075
TI  - The neurobehavioural toxicity of endosulfan in rats: a serotonergic involvement
      in learning impairment.
AB  - Oral administration of the insecticide endosulfan (2 mg/kg per day) for 90 days
      in immature male rats resulted in an inhibition of pole-climbing escape response
      to electric shock (unconditioned) and avoidance response to buzzer (conditioned).
      These responses reflect respectively their learning and memory processes. The
      escape response but not the avoidance response was reinstated significantly by
      the 5-hydroxytryptamine (5-HT) depletor, p-chlorophenylalanine (PCPA, 100 mg/kg
      per day for 3 days). Endosulfan increased 5-HT concentrations in the cerebrum and
      midbrain regions. Protein content and acetylcholinesterase activity were
      unaltered in the brain. The spontaneous motor activity of these animals was
      stimulated. Their muscle coordination on rota-rod apparatus was unaffected. These
      findings were interpreted as an indication that a motivation deficit and not
      motor impairment was responsible for the inhibitory action of endosulfan on pole
      climbing escape and avoidance responses. Thus, endosulfan was suggested to
      produce learning and memory deficit. A serotonergic involvement was significant
      in endosulfan-induced learning impairment and it appeared to be negligible in its
      memory disrupting action.

PMID- 8157076
TI  - Elevated temperature accelerates and amplifies the induction of nitric oxide
      synthesis in rat macrophages.
AB  - Evidence has accrued that nitric oxide (NO) is an effector molecule in cell
      mediated immunity, and it is generally agreed that fever is beneficial to host
      defence. Therefore, the role of elevated temperature in the induction of NO
      synthesis was examined in rat peritoneal macrophages activated by
      lipopolysaccharide (LPS). When macrophages were incubated in vitro at 40 degrees
      C, the time between macrophage activation and the induction of NO synthesis, as
      assessed by nitrite accumulation in the medium, was shortened as compared with
      incubation at 37 degrees C, and nitrite accumulation was markedly enhanced by 2.6
      and 1.8-fold after 6 and 9 h of LPS activation, respectively. These results
      suggest that elevated temperature may contribute to enhance host defence by
      accelerating and amplifying the induction of NO synthesis in macrophages.

PMID- 8157077
TI  - Increased glomerular nitric oxide synthesis in gentamicin-induced renal failure.
AB  - Renal glomeruli isolated from normal rats and from rats with gentamicin-induced
      renal failure were incubated with substances that modify nitric oxide (NO)
      synthesis and the resulting changes in glomerular cyclic GMP (cGMP) levels were
      measured by radioimmunoassay. Glomeruli from normal and gentamicin-treated rats
      contained 0.17 +/- 0.04 and 2.02 +/- 0.63 pmol cGMP/mg protein respectively. In
      normal glomeruli, acetylcholine and bradykinin significantly increased cGMP
      levels whereas NG-nitro-L-arginine-methyl ester, an inhibitor of NO synthesis,
      completely blocked this increase. In glomeruli from gentamicin-treated animals,
      acetylcholine and bradykinin also stimulated cGMP accumulation, while NG-nitro-L
      arginine-methyl ester decreased the cGMP content to levels significantly below
      the basal concentrations. These data suggest an increased glomerular production
      of NO in rats with gentamicin-induced renal failure.

PMID- 8157078
TI  - Effect of ethanol on extracellular 5-hydroxytryptamine output in rat frontal
      cortex.
AB  - The effect of acute administration of ethanol on the release of 5
      hydroxytryptamine (5-HT) in the frontal cortex of "Sardinian alcohol preferring"
      rats, "Sardinian non-preferring" rats and control rats was investigated using in
      vivo microdialysis. At the dosage of 2.5 g/kg i.p. ethanol increased the level of
      5-HT in the dialysate by approximately 80 +/- 20% of basal values in the
      Sardinian alcohol preferring rats whereas no effect was observed in Sardinian non
      preferring and control rats.

PMID- 8157079
TI  - Diet-induced atherosclerosis inhibits release of noradrenaline from sympathetic
      nerves in rabbit arteries.
AB  - Contractile responses to sympathetic nerve stimulation and exogenous
      noradrenaline were compared in aortas and pulmonary arteries of control rabbits
      and rabbits fed a cholesterol-rich diet (0.3%) for 16 or 30 weeks. The diet
      induced atherosclerosis reduced the contractions to increasing concentrations of
      exogenous noradrenaline (0.1 nM to 10 microM) in both arteries, and the reduction
      was more pronounced after 30 weeks of the hypercholesterolemia. The contractions
      produced with increasing frequencies of electrical stimulation (1-32 Hz) were
      nearly abolished in the atherosclerotic arteries. Labeling of the aorta and the
      pulmonary arteries with [3H]noradrenaline resulted in accumulation of
      radioactivity in both control and atherosclerotic blood vessels. After mounting
      the labeled blood vessels for superfusion, a basal efflux of [3H]noradrenaline
      and of 3H-metabolites was detected. In the atherosclerotic arteries, a decreased
      efflux of the intraneuronal deaminated metabolites 3,4-dihydroxyphenyl glycol
      (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) was detected. Electrical
      stimulation at 1 Hz (pulmonary artery) or 2 Hz (aorta) caused an augmented efflux
      of total 3H from the control arteries; this was mostly due to release of intact
      [3H]noradrenaline. The electrical impulses evoked significantly less (16 weeks)
      or no (30 weeks) release of [3H]noradrenaline in the atherosclerotic arteries.
      These data illustrate that diet-induced atherosclerosis exerts an inhibitory
      action on the sympathetic nerve terminals in the aorta and the pulmonary artery
      of the rabbit. This effect, together with an inhibitory effect at the
      postjunctional level results in a loss of the responsiveness to nerve
      stimulation. The atherosclerotic process also inhibits the intraneuronal
      deamination of the sympathetic transmitter.

PMID- 8157080
TI  - Cocaine N-demethylation and the metabolism-related hepatotoxicity can be
      prevented by cytochrome P450 3A inhibitors.
AB  - Cocaine is eliminated and detoxified principally through the metabolism of
      nonspecific plasma and tissue esterases. Microsomal oxidative metabolism is of
      importance in cocaine N-demethylation, this being a principal pathway of cocaine
      bioactivation and hepatotoxicity. The contribution of different cytochrome P450
      (CYP) enzymes to cocaine N-demethylase activity was studied in vitro with DBA/2
      mouse and human liver microsomes, and cocaine hepatotoxicity was examined in vivo
      in DBA/2 male mice. Species dependent enzyme kinetics was observed. Cocaine N
      demethylase displayed two Km values in murine liver (40-60 microM and 2-3 mM),
      whereas only one Km value was observed in human liver microsomes (2.3-2.7 mM). We
      suggest that CYP3A plays a prominent role in the N-demethylation of cocaine for
      the following reasons: (i) pregnenolone-16 alpha-carbonitrile, an inducer of
      CYP3As increases cocaine N-demethylase in parallel with testosterone 6 beta
      hydroxylase activity and immunoreactive 3A protein in mouse liver; (ii) human and
      mouse cocaine N-demethylase and testosterone 6 beta-hydroxylase activities can be
      inhibited by triacetyloleandomycin, cannabidiol, or gestodene, all selective
      inhibitors of CYP3A P450s; (iii) antibodies directed against P450s within
      subfamilies 1A, 2A, 2B, 2C, or 2E inhibited cocaine N-demethylase activity only
      marginally, and finally, (iv) treatment of mice with triacetyloleandomycin or
      cannabidiol in vivo significantly attenuated the cocaine-elicited hepatotoxicity
      as assessed by the serum alanine aminotransferase activity and liver histology in
      parallel with decreased cocaine N-demethylase activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8157081
TI  - High passage T47D human breast cancer cells: altered endocrine and 2,3,7,8
      tetrachlorodibenzo-p-dioxin responsiveness.
AB  - Low passage (L) T47D cells cultured for up to 12 months in media containing fetal
      bovine serum, fetal bovine serum plus 1 nM 17 beta-estradiol and estrogen
      deficient media gave high passage cells denoted H, H(E+) and H(E-) cells,
      respectively, which exhibited differential responsiveness to 17 beta-estradiol,
      various growth factors, tamoxifen, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and their
      combinations. Moreover, the altered mitogen/antimitogen responsiveness was
      paralleled by changes in hormone receptor levels, cellular architecture and
      ploidy. Estrogen receptor binding levels in the H, L and H(E+) cells varied from
      36 to 155 fmol/mg protein; in contrast, the estrogen receptor binding in H(E-)
      cells exhibited a time-dependent increase from 81 to 1229 fmol/mg after culturing
      in estrogen-deficient media for approximately 12 months. Gel mobility shift
      assays of the nuclear estrogen receptor extracts from high and low passage cells
      with 32P-labeled estrogen responsive element showed that levels of the estrogen
      receptor-estrogen responsive element retarded band were lower in all the high
      passage cells compared to the low passage cells. These studies further illustrate
      the genetic instability of the T47D human breast cancer cell line and the
      resulting changes in mitogen and antimitogen responsiveness. In addition, the
      high passage H(E-) cells which express high estrogen receptor but low estrogen
      responsive element binding represent a unique model system for investigating the
      cellular and molecular biology of breast cancer cells which appear to be estrogen
      receptor-positive but are insensitive to antiestrogens.

PMID- 8157082
TI  - The NMDA receptor agonist DL-(tetrazol-5-yl)glycine is a highly potent
      excitotoxin.
AB  - DL-(Tetrazol-5-yl)glycine is a highly selective N-methyl-D-aspartate (NMDA)
      receptor agonist with nanomolar in vitro potency. Previous work showed that DL
      (tetrazol-5-yl)glycine has greater affinity and efficacy at NMDA receptors than
      other NMDA receptor agonists such as cis-methanoglutamate and NMDA. In this
      study, the in vivo excitotoxic potency of DL-(tetrazol-5-yl)glycine was compared
      to cis-methanoglutamate and NMDA. Adult (250-300 g) and neonatal (7-day-old) rats
      were anesthetized and compounds were unilaterally injected into the striatum. In
      adult rats DL-(tetrazol-5-yl)glycine (0.3-1.0 nmol/microliters) produced highly
      significant losses of striatal gamma-aminobutyric acid neurons (as indexed by
      glutamic acid decarboxylase activity) and cholinergic neurons (as indexed by
      choline acetyltransferase activity). Dose-response showed that DL-(tetrazol-5
      yl)glycine was about 100 and 500 times more potent than cis-methanoglutamate and
      NMDA, respectively. In neonatal rats, DL-(tetrazol-5-yl)glycine (0.1-0.3
      nmol/microliters) produced significant brain damage as indicated by brain weight
      losses 5 days later. DL-(Tetrazol-5-yl)glycine was about 50 and 150 times more
      potent than cis-methanoglutamate and NMDA, respectively, in the neonate. The
      excitotoxic potency of DL-(tetrazol-5-yl)glycine is likely due to its greater
      efficacy and potency at the NMDA receptor, when compared to other NMDA receptor
      agonists. The remarkable in vivo potency of DL-(tetrazol-5-yl)glycine in
      producing excitotoxic lesions makes it a useful agent to further probe NMDA
      receptor mediated excitotoxicity in brain pathologies.

PMID- 8157083
TI  - Zinc hydroxide induced respiratory burst in rat neutrophils.
AB  - The effects of zinc hydroxide on the respiratory burst and phagocytosis by rat
      neutrophils were examined. Zinc hydroxide induced an increase in oxygen
      consumption and O2- production. Electronmicroscopy showed that neutrophils
      engulfed zinc hydroxide particles by phagocytosis. Pertussis toxin (0.25, 0.5,
      1.0 micrograms/ml) and EGTA (1, 2, 5 mM) inhibited zinc hydroxide-induced O2-
      production in a dose-dependent manner. The inhibitors of protein kinase C, 1-(5
      isoquinolinesulfonyl)-2-methyl-piperazine and N-[2-(methylamino)ethyl]-5
      isoquinolinesulfonamide inhibited zinc hydroxide-induced O2- production with IC50
      values ranging between 10 microM and 25 microM. The inhibitory study using an
      inhibitor of myosin light chain kinase, 1-(5-iodo-naphthalene-1-sulfonyl)-1H
      hexahydro-1,4-diazepine, showed IC50 values ranging from 5 microM to 10 microM.
      These findings indicate that zinc hydroxide induces respiratory burst and
      phagocytosis by rat neutrophils.

PMID- 8157084
TI  - Antiproliferative and cytotoxic profiles of antipsoriatic fumaric acid
      derivatives in keratinocyte cultures.
AB  - Oral administration with complex mixtures of fumaric acid derivatives is known to
      have antipsoriatic efficacy. The present studies aimed to clarify the mode of
      action and toxicity of the individual compounds. Hyperproliferative HaCaT
      keratinocytes in monolayer cultures were exposed to fumaric acid,
      dimethylfumarate, zinc monoethylfumarate, calcium monoethylfumarate and magnesium
      monoethylfumarate at concentrations between 0.4 microM and 960 microM for 48 h.
      Cell proliferation was studied by [3H]thymidine incorporation. In addition 14C
      labelled amino acid uptake and total protein content were measured. Direct
      cytotoxicity was determined by the release of cytoplasmic lactate dehydrogenase
      (LDH) into the culture medium. The corresponding 50% inhibition concentrations
      (IC50) were calculated for DNA/protein synthesis: 2.3/2.5 microM
      (dimethylfumarate), 133/145 microM (zinc monoethylfumarate), 215/230 microM
      (calcium monoethylfumarate), 275/270 microM (magnesium monoethylfumarate), >
      960/> 960 microM (fumaric acid). The total protein content was less sensitive.
      Antiproliferative activity was found for dimethylfumarate and to a lesser degree
      for calcium monoethylfumarate already at the subtoxic concentrations of 1.3 and 4
      microM, respectively. In the case of magnesium monoethylfumarate, zinc
      monoethylfumarate and fumaric acid there was no such dissociation between their
      cytotoxic and antiproliferative potential. These data indicate that most of the
      antipsoriatic potential of fumaric therapies is due to the dimethylfumarate
      compound.

PMID- 8157085
TI  - Relaxation of rat thoracic aorta induced by 2,2',2''-tripyridine.
AB  - The pharmacological and toxicological activity of 2,2',2''-tripyridine was
      determined in rat thoracic aorta. 2,2',2''-Tripyridine inhibited norepinephrine
      (3 microM)-induced phasic and tonic contractions in the thoracic aorta as well as
      the endothelium-denuded aorta of the rat. The tonic pre-contraction elicited by
      norepinephrine was also relaxed by the addition of 2,2',2''-tripyridine and this
      relaxing effect was not affected by indomethacin (20 microM) but partially
      antagonized by methylene blue (50 microM). In high-K+ medium (80 mM), 2,2',2''
      tripyridine inhibited the Ca2+ concentration dependent vasocontraction. Moreover,
      in Ca(2+)-free medium, the phasic contraction induced by either norepinephrine (3
      microM) or caffeine (10 mM) was also suppressed by 2,2',2''-tripyridine. Although
      the cAMP level of rat aorta was not changed by 2,2',2''-tripyridine, cGMP level
      was significantly increased by 2,2',2''-tripyridine. The increase in cGMP level
      caused by 2,2',2''-tripyridine was completely blocked by methylene blue (50
      microM). The 45Ca2+ influx elicited by either norepinephrine or high-K+ was
      inhibited by 2,2',2''-tripyridine. All of these findings indicate that 2,2',2''
      tripyridine relaxes rat thoracic aorta by virtue of its Ca(2+)-channel blocking
      properties and by elevating cGMP levels in vascular smooth muscle.

PMID- 8157086
TI  - Contribution of direct actions of the oxime HI-6 in reversing soman-induced
      muscle weakness in the rat diaphragm.
AB  - The actions of the bispyridinium oxime HI-6 ([[[(4-aminocarbonyl)pyridino]
      methoxy]methyl]-2- [(hydroxyimino)methyl]-pyridinium dichloride) were
      investigated in vitro on rat phrenic nerve-hemidiaphragm preparations. Isometric
      twitch and tetanic tensions were elicited at 37 degrees C with supramaximal nerve
      stimulation at frequencies of 20 and 50 Hz. To approximate normal respiration
      patterns, trials consisting of 30 successive 0.55 s trains were alternated with
      1.25 s rest periods. Under control conditions, the above stimulation pattern
      generated tensions that were well maintained at both frequencies. In contrast, a
      marked depression of muscle tension was observed in diaphragms removed from rats
      administered 339 micrograms/kg soman (3 LD50) and tested in vitro. Addition of HI
      6, 4 h after soman exposure, led to a nearly complete recovery of muscle tension
      at 20 Hz. At 50 Hz, muscle tensions still declined especially when trains were
      elicited at 1.25 and 3 s intervals. The recovery by HI-6 observed in this study
      appears to be mediated by mechanisms unrelated to acetylcholinesterase
      reactivation since no increase of enzymatic activity was detected and the effect
      was reversed by a brief washout in oxime-free physiological solution. The results
      suggest that the direct action of HI-6 may play a role in restoring soman-induced
      diaphragmatic failure but this effect would be significant primarily under low
      use conditions.

PMID- 8157087
TI  - Acute effects of gentamicin on thick ascending limb function in the rat.
AB  - It is well established that the aminoglycoside antibiotics can adversely affect
      proximal tubule function. Predominantly indirect evidence suggests that
      aminoglycosides may also affect function of more distal nephron segments. The
      present study utilized whole kidney clearance, in vivo micropuncture and in vitro
      microperfusion to directly determine whether acute gentamicin treatment affects
      sodium chloride transport in the thick ascending limb of the loop of Henle.
      Gentamicin (25 mg/kg) significantly increased urine flow, as well as sodium,
      potassium and chloride excretion within 15 min of intravenous injection.
      Glomerular filtration rate and proximal tubule fluid reabsorption were not
      altered by acute gentamicin treatment. In contrast, both fractional and absolute
      loop chloride transport was significantly decreased. In the in vitro
      microperfused medullary thick ascending limb, luminal but not basolateral
      administration of gentamicin (1 mM) significantly decreased chloride reabsorption
      when compared to time controls. These data suggest that the increased urine and
      electrolyte excretion associated with acute gentamicin treatment is, at least in
      part, a consequence of decreased transport in the thick ascending limb of Henle's
      loop.

PMID- 8157088
TI  - Islet transplantation. The connection of experiment and clinic exemplified by the
      transplantation of islets of Langerhans.
AB  - Since approximately 25 years islet transplantation as a mean for the treatment of
      diabetes has been developed from early attempts in rodents to first clinical
      applications in man in recent years. The review describes the results obtained in
      diabetic rats including metabolic effects as well as prevention of late
      complications. In the syngeneic system (Lewis-rats) the intraportal
      transplantation of 1,000-2,000 isolated islets may cure streptozotocin-induced
      diabetes for the whole lifespan of the animal. In the allogeneic system (across a
      major histocompatibility barrier), however, isolated islets are highly
      immunogenic. According to present knowledge, mainly class-II antigen bearing
      cells are responsible while the role of the endocrine cells seems to be less
      important. By various in vitro methods (e.g. low temperature culture at 24
      degrees C) it was possible to induce immunoalteration of allogeneic islets which
      was followed by long-term acceptance by the host in rodents. Whether the same
      technique is effective in larger animals and in man remains open. New
      technologies for the isolation of high numbers of pure islets from human
      pancreatic glands have been the key for the use of islet transplantation in man
      in several centers. The review describes the details regarding institutions as
      well as results in patients on the basis of the International Islet Transplant
      Registry which is located at Giessen University. Although longer lasting insulin
      independency (longest lasting effect 2 1/2 years) has been observed only in a few
      patients, islet transplantation has been proven to be a very safe procedure for
      the patient. It is hoped that with increasing experiences regarding the factors
      which at present limit the function as number and quality of islets,
      immunosuppressive protocols etc. islet transplantation will develop to a definite
      alternative to whole-organ transplantation. One of the most important challenges
      for modern medicine is the fact of a worldwide increase of diabetic long-term
      complications such as kidney failure, coronary and peripheral vascular disease,
      blindness and neuropathy. Although intensified insulin treatment in a small
      percentage of patients may moderate morbidity and mortality, from experimental
      work there is sufficient evidence suggesting that only the restoration of
      normoglycemia early in the course of the disease may prevent complications. This,
      however, can only be achieved by the replacement of the destroyed islets of
      Langerhans either by transplantation of an intact vascularised pancreas or by
      isolated islets.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8157089
TI  - Elevated serum thyrotropin [TSH] levels in critically ill patients with acquired
      immunodeficiency syndrome (AIDS).
AB  - STUDY OBJECTIVE: To determine thyrotropin (TSH) reserve in critically ill
      patients with Acquired Immunodeficiency Syndrome (AIDS). DESIGN: Prospective
      longitudinal. SETTING: Six hundred (600) bed municipal hospital serving a poor
      neighborhood in New York City with a high incidence of AIDS mainly from
      intravenous drug abuse. PATIENTS AND METHODS: Twelve (12) patients with AIDS, who
      were in the Intensive Care Unit or critically ill on medical wards, were
      evaluated consecutively with baseline thyroid function tests and serum
      thyrotropin (TSH) response to thyroid releasing hormone testing. RESULTS: 66.7%
      of patients had elevated TSH levels. All patients had low triiodothyronine (T3),
      six patients had low thyroxine (T4) levels. RESULTS: (cont'd). Six patients met
      the criteria for hypothyroidism. Two patients met the criteria for subclinical
      hypothyroidism. CONCLUSION: Elevated TSH levels and hypothyroidism are common in
      our critically ill population with AIDS.

PMID- 8157090
TI  - Effects of angiotensin II and atrial natriuretic peptide on LH release are
      exerted in the preoptic area: possible involvement of gamma-aminobutyric acid
      (GABA).
AB  - The preoptic/anterior hypothalamic area (PO/AH) contains the majority of LHRH
      neurons of which the function is regulated by a variety of neurotransmitters and
      peptides. In this area, numerous estrogen-receptive neurons utilize
      gammaaminobutyric acid (GABA) as neurotransmitter and these neurons communicate
      directly with LHRH neurons. Angiotensin II (AII) and atrial natriuretic peptide
      (ANP) are known to be involved in the regulation of LH secretion. The site of
      action of these peptides and the mechanisms by which they influence LHRH neurons,
      are largely unknown. Therefore the effects of intrapreoptic application of AII
      and ANP on serum LH levels of ovariectomized (ovx) and of ovx estrogen-primed
      rats were investigated. The peptides were applied into the PO/AH by means of push
      pull cannula and in the effluent fractions GABA was measured. In the ovx estrogen
      primed rat, prominent LH and prolactin surges were observed. At the time of
      increased LH levels preoptic GABA release was significantly reduced. At this time
      application of AII or ANP into the PO/AH was without effect on either LH or
      prolactin levels in the serum or on preoptic GABA release rates. In ovx, not
      steroid-primed rats intrapreoptic AII application suppressed serum LH levels
      significantly and this treatment had a slight stimulatory effect on preoptic GABA
      release rates. This effect of AII could be antagonized by prior preoptic
      treatment with saralasin, a specific AII receptor blocking peptide. Preoptic
      treatment with ANP resulted in a slight increase in serum LH levels which was
      accompanied by a slight, but significant reduction of preoptic GABA release
      rates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157091
TI  - The male-induced implantation failure (the Bruce effect) in mice: effect of
      exogenous progesterone on maintenance of pregnancy in male-exposed females.
AB  - The effect of exogenous progesterone given early during pregnancy in maintaining
      pregnancy in alien male-exposed mice was investigated. Administration of
      progesterone, 1 mg/female/day, on days 1 to 5 post coitum was fully effective and
      on day 2 to 6 post coitum was partially effective in maintaining pregnancy in
      females. However, progesterone injection on days 3 to 7 post coitum was totally
      ineffective in maintaining pregnancy in females. The results suggest that only
      when administration of progesterone is begun early during male exposure, luteal
      failure in newly inseminated females is prevented. The results also suggest that
      failure of corpus luteum function or some other irreversible changes leading to
      luteolysis occur in females early during exposure to alien males before the
      external manifestation of implantation failure (vaginal cornification). It is
      suggested that exogenous progesterone given early during alien male exposure
      prevents luteal failure and maintains pregnancy in females through its
      facilitatory effect on hypophysial prolactin secretion.

PMID- 8157092
TI  - Insulin action in patients with insulinoma influenced by pharmacological and
      surgical therapy.
AB  - Organic hyperinsulinism due to insulinoma is accompanied by changes of insulin
      action on receptor and postreceptor levels. The influence of conservative and
      surgical treatment on insulin sensitivity was examined by euglycaemic
      hyperinsulinaemic clamps in ten patients with insulinoma. The "responders" (n =
      5) and "non-responders" (n = 5) to diazoxide treatment were distinguished by
      using fasting plasma glucose and insulin concentrations. The index of insulin
      sensitivity was significantly decreased in pretreated "responders" as compared to
      healthy persons (19 +/- 3 vs 39 +/- 6 and 20 +/- 3 vs 37 +/- 5 mumol.kg-1.min-1
      per mU.l-1 x 100, p < 0.01) and it was improved during diazoxide administration
      (27 +/- 4 vs 19 +/- 3 and 35 +/- 12 vs 20 +/- 3 mumol.kg-1.min-1 per mU.l-1 x
      100, p < 0.05). Significantly decreased insulin sensitivity in pretreated "non
      responders" (25 +/- 5 vs 39 +/- 6 and 28 +/- 6 vs 37 +/- 5 mumol.kg-1.min-1 per
      mU.l-1 x 100, p < 0.05) was not improved by diazoxide administration. Metabolic
      clearance rate of glucose was significantly higher in "non-responders" as
      compared to "responders" and healthy persons (12.7 +/- 3.4 vs 7.9 +/- 2.7 and 7.4
      +/- 2.4 ml.min-1.kg-1, p < 0.05) already in pretreated state. An inverse
      relationship was found between metabolic clearance rate of glucose and of insulin
      (r = 0.72, p < 0.001). Plasma glucose, insulin concentration, index of insulin
      sensitivity, and metabolic clearance rate of glucose and of insulin were
      normalized after surgical removal of an insulinoma in all patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8157093
TI  - Leydig cell neoplasia in a patient with Reifenstein syndrome.
AB  - We present the rare coincidence of a Leydig cell tumor in both testicles of a
      patient with partial androgen insensitivity syndrome (PAIS). The clinical picture
      with perineoscrotal hypospadia, micropenis, gynecomastia and delayed puberty and
      the serum hormone levels with elevated concentrations of testosterone,
      luteinising hormone (LH) and follicle-stimulating hormone were entirely
      consistent with PAIS. Ultimately, the diagnosis was confirmed by determination of
      genital skin fibroblast androgen receptor binding capacity for 5 beta
      dihydrotestosterone, which demonstrated a qualitatively abnormal androgen
      receptor. At 44 years of age, a nodule in the left testis led to orchidectomy. At
      that time, the right testis was inconspicuous sonographically. But 3 years later
      the right testis developed nodules and was removed. Review of testicular
      histology revealed the presence of Leydig cell hyperplasia (LCH), multifocal
      nodular hyperplasia and Leydig cell neoplasia (LCN) in both testes. Many
      micronodules of Leydig cells in transition from hyperplasia to neoplasia were
      also identified. The simultaneous development of histologically identical nodes
      of LCN independently from each other and a different sites of both tests
      indicates the presence of a tumorigenic factor acting on the Leydig cells.
      Furthermore, the observation of multiple foci of cells in all stages of
      transition from hyperplasia to neoplasia demonstrates the persistent process of
      transformation. We speculate, that in this patient the grossly elevated LH levels
      present over 30 years have enhanced, if not provoked, the formation of LCN. In
      addition, the defective androgen receptor might have prevented suppressive
      effects of androgens on the Leydig cells.

PMID- 8157094
TI  - Atrial natriuretic peptide-like immunoreactive material (ANP-LI) is released from
      the adrenal gland by splanchnic nerve stimulation.
AB  - We investigated the release of atrial natriuretic peptide-like immunoreactive
      material (ANP-LI) after splanchnic nerve stimulation of isolated perfused adrenal
      glands. Electrical stimulation of the splanchnic nerves caused a statistically
      significant increase of ANP-LI (186 +/- 12 pg.min-1; p < 0.05) at 5 min. after
      stimulation. The integrated ANP-LI release after stimulation was amounted to 354
      +/- 6.8% over basal. The regulation of ANP through the sympathoadrenal system may
      indicate an important role of ANP in adrenal steroidogenesis.

PMID- 8157095
TI  - Loss of diurnal arrestin gene expression in rds mutant mouse retinas.
AB  - Despite the important advances in the molecular analysis of retinal
      degenerations, the causes of photoreceptor cell death in these conditions are
      unclear. To explore the metabolic impact of the rds mutation, we have continued
      our investigations on the expression of arrestin. Normal BALB/c mouse retinas
      have a diurnal variation in arrestin gene expression and protein biosynthesis,
      with low levels in dark-adapted and high levels in the light-adapted retinas. In
      contrast, arrestin is expressed in rds retinas at high levels throughout the
      diurnal cycle. A lack of a distinct diurnal cycle and continuously high
      expression of arrestin in rds retinas might be a reflection of metabolic
      derangements in these cells which are not an obvious consequence of the
      underlying molecular defect in the rds/peripherin gene.

PMID- 8157096
TI  - Pharmacokinetics, acid-base balance and intraocular pressure effects of
      ethyloxaloylazolamide--a novel topically active carbonic anhydrase inhibitor.
AB  - Studies evaluated a novel series of biscarbonylamides of 2-amino-1,3,4
      thiadiazole-5-sulfonamide (2-ATS) for topical use as ocular hypotensive carbonic
      anhydrase inhibitors (CAI). Transcorneal accession rate constants (k(in)) for
      ethyloxaloylazolamide (EtOxAz), ethylsuccinylazolamide (EtSuxAz) and
      ethyladipoylazolamide (EtAdipAz), and activity against carbonic anhydrase (CA)
      were determined in vitro by an enzymatic assay and High Performance Liquid
      Chromatography (HPLC). The ocular hypotensive effect was measured by
      pneumatonometry on conscious normotensive New Zealand White (NZW) rabbits, using
      masked, randomly assigned paired-eye design for treatment vs. control. At various
      time points following treatment, aqueous humor, ciliary processes and corneal
      buttons were collected and assayed for drug concentrations using enzymatic assay
      and HPLC. Transcorneal accession rates for the novel compounds were 1.5 to 18
      times that of the parent compound, acetazolamide (Actz). The activity factor for
      EtOxAz was 72.8 x 10(3) hr-1 of 23 times that of Actz. The activity factors for
      EtSuxAz and EtAdipAz were 6.8 and 1.1 x 10(3) hr-1, respectively. Subcutaneous
      administration of EtOxAz. EtSuxAz, and EtAdipAz, in 225 mumol kg-1
      concentrations, induced a significant decrease in the intraocular pressure (IOP)
      at 1 hr post injection of 4, 5.8 and 6 mmHg for EtOxAz, EtSuxAz and EtAdipAz,
      respectively (P < 0.05 for each). Topical application of 75 mM EtOxAz lowered the
      IOP by 3.0 mmHg (P < 0.05). This effect was maximal after 60 min and persisted
      for at least 5 hr. EtSuxAz and EtAdipAz did not alter the IOP significantly when
      given topically. Subcutaneous administration of the three compounds was
      associated with acidosis (pH as low as 7.21). Topical application did not cause
      any changes in the acid-base balance. There was a direct correlation between the
      amount of drug delivered to the ciliary process and the magnitude of ocular
      hypotensive effect. Following topical application EtOxAz reached the ciliary
      epithelium in concentrations sufficient to inhibit more than 99.95% of the
      ciliary carbonic anhydrase (> 8 microM), while plasma drug concentrations were
      below the limit of detection by the assay (< 0.2 microM). Within the first hour
      after topical application, half of the EtOxAz was eliminated from the anterior
      uvea. In summary, EtOxAz is a topically effective CAI. Structural modifications
      of thiadiazole sulfonamides, with the increase of both water and lipid
      solubilities, improved the transcorneal accession while preserving sufficient CA
      inhibitory activity, resulting in a significant IOP decrease following topical
      application of EtOxAz.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157098
TI  - On the intracellular stability of lens crystallins.

PMID- 8157097
TI  - Neuronal pathways to the rat conjunctiva revealed by retrograde tracing and
      immunocytochemistry.
AB  - The origin and neuropeptide content of nerve fibres in the rat conjunctiva were
      studied by retrograde tracing and denervations in combination with
      immunocytochemistry. Immunocytochemistry revealed nerve fibres containing
      neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), peptide histidine
      isoleucine (PHI), helospectin, substance P (SP), and calcitonin gene-related
      peptide (CGRP) around blood vessels, smooth muscle bundles and glands. Removal of
      the sphenopalatine ganglion eliminated the majority of the VIP-, PHI- and
      helospectin-containing fibres. Sympathectomy eliminated the majority of the NPY
      containing fibres in the conjunctiva. Removal of both the sphenopalatine ganglion
      and the superior cervical ganglion led to further reduction of the NPY fibres.
      Injection of the retrograde tracer True Blue into the conjunctiva resulted in the
      appearance of labelled cell bodies in the trigeminal ganglion, the sphenopalatine
      ganglion, the superior cervical ganglion, and the ciliary ganglion. Judging from
      the number of labelled nerve cell bodies, the superior cervical ganglion
      contributes most to the innervation. These results indicate that the majority of
      NPY-containing nerve fibres in the conjunctiva derives from the superior cervical
      ganglion (sympathetic nerve supply). Most of the VIP- and a minor population of
      the NPY-containing fibres in the conjunctiva originate in the sphenopalatine
      ganglion (parasympathetic nerve supply). A sparse amount of VIP- and NPY
      containing fibres derives from the ciliary ganglion. Nerve fibres containing SP
      and/or CGRP emanate from the trigeminal ganglia (sensory nerve supply). Together
      the findings indicate that several ganglia project to the conjunctiva and that
      many neuropeptides may be involved in the control of conjunctival activity.

PMID- 8157099
TI  - Blue-light-induced dysfunction of the blood-retinal barrier at the pigment
      epithelium in albino versus pigmented rabbits.
AB  - The purpose of this study was to determine the role of epithelial melanin in blue
      light phototoxicity of the retina. The first manifestation of the phototoxicity
      has been shown to be a breakdown of the blood-retinal barrier at the retinal
      pigment epithelium. The blood-retinal barrier function of six New Zealand albino
      rabbits was compared to that of four pigmented chinchilla rabbits after exposure
      to broad-band blue light (400-520 nm). Additionally, the spectral sensitivity of
      blood-retinal barrier dysfunction was determined by exposing 15 New Zealand
      albino rabbits to narrow-band blue light with peak intensity at lambda = 408 nm,
      418 nm, 439 nm, 455 nm and 485 nm (bandwidth: 11.7-13.5 nm). The blood-retinal
      barrier function was evaluated with vitreous fluorophotometry. Ultrastructural
      changes and permeability of the retinal pigment epithelium for horseradish
      peroxidase were evaluated in the albino rabbits with electron microscopy.
      Exposure to broad-band blue light up to 832 J cm-2 demonstrated the blood-retinal
      barrier of albino and pigmented rabbits to be equally sensitive. Electron
      microscopy of albino rabbits exposed to above-threshold energy demonstrated an
      increase of inclusion bodies in the retinal pigment epithelium and vacuolation of
      the cytoplasm. Transcellular passage of intra-arterially administered horseradish
      peroxidase through the pigment epithelium into the subretinal space was seen. The
      narrow-band exposures demonstrated that light of 439 nm was more effective than
      the light of other wavelengths in inducing barrier dysfunction in albino rabbits.
      This implies that chromophores absorbing at 439 +/- 6 nm were responsible for the
      phototoxicity in albino rabbits. The results indicate that melanin does not have
      a damaging nor a protective role in phototoxicity since (1) the presence of
      melanin is not essential for blue-light-induced photochemical damage to the blood
      retinal barrier at the retinal pigment epithelium, and (2) protection from this
      sort of damage is not greater in melanin containing epithelia than in non-melanin
      containing epithelia.

PMID- 8157100
TI  - Expanded fluorocarbon for keratoprosthesis cellular ingrowth and transparency.
AB  - The development of a synthetic material allowing increased cellular adhesion and
      ingrowth would improve keratoprosthetic devices and requires an understanding of
      cell colonization processes. Interlamellar implantation of hydrophobic synthetic
      material may lead to poor corneal nutrition with subsequent necrosis. The
      probability of necrosis increases with material which is more impermeable, larger
      in diameter and more anterior in its placement. In this study we demonstrated the
      importance of pore diameter in the rate and density of cell colonization. We
      demonstrated that an opaque hydrophobic material may become translucent and
      wettable with very low perturbation of flow through the cornea. We used an
      expanded polytetrafluoroethylene with either 20 microns or 50 microns pore
      diameter. Cellular ingrowth was significantly greater in the material with 50
      microns pores, resulting in collagen deposition within the pores without corneal
      vascularization at 6 months follow-up. Immunohistochemical study with monoclonal
      antibody AE5 revealed normal epithelial differentiation on the surface of the
      cornea over the implanted polymer.

PMID- 8157101
TI  - Localization of collagen type III mRNA in normal human optic nerve heads.
AB  - Previous studies using immunocytochemistry and electron microscopy have localized
      collagen type III (CIII) in the human optic nerve head (ONH). CIII is present in
      the core of the cribriform plates of the lamina cribrosa and increases with age.
      In this study, in situ hybridization was used to localize mRNA for CIII in
      specific cells in human fetal and adult ONH to determine its cellular origin and
      to provide temporal and regional information on the synthesis of CIII in the ONH.
      Human ONH from donors with no history of eye disease (16-24 weeks gestation and 6
      75 years) were fixed, embedded and sectioned serially. Sections were hybridized
      with antisense riboprobe for CIII and controls with sense riboprobe and processed
      for ISH. Immunoperoxidase staining with antibodies against GFAP and von
      Willebrand factor was used to detect astrocytes and vascular endothelial cells
      respectively. Fetal ONH: CIII mRNA was localized in most blood vessels throughout
      the ONH in sections hybridized with antisense probe. The label was localized to
      endothelial cells of small vessels. Endothelial cells of central retinal vessels
      were not labeled. In the lamina cribrosa, CIII mRNA was localized to small
      vessels, but not to astrocytes. Fibroblasts of the peripapillary sclera were
      labelled with antisense probe. Young-Adult ONH: In the cribriform plates, lamina
      cribrosa cells hybridized the probe at all ages. Few astrocytes hybridized the
      probe. Some endothelial cells of small vessels were also labeled. In the
      insertion region, most vessels were labeled in young ONH, but very few, if any,
      in old adults. The apparent intensity of hybridization signal associated with
      blood vessels in adult ONH is markedly reduced with age. No hybridization was
      observed inside of nerve bundles consistent with the absence of mRNA inside axon
      and CIII in this location. Localization of mRNA for CIII to blood vessels in
      fetal lamina cribrosa suggests a vascular origin for CIII in the plates, and
      perhaps, for lamina cribrosa cells. In young and old lamina cribrosa,
      localization of CIII mRNA suggests lifelong synthesis of this protein in
      agreement with age-related increase of CIII in this tissue.

PMID- 8157102
TI  - Light deprivation profoundly affects gene expression of interphotoreceptor
      retinoid-binding protein in the mouse eye.
AB  - Ambient light appears to play a role in regulating gene and protein expression of
      interphotoreceptor retinoid-binding protein (IRBP), a protein that facilitates
      the transport of retinoids between the neural retina and pigment epithelium in
      the visual cycle. Pregnant CD-1 mice were placed in the dark approximately 48 hr
      before parturition, and the pups were reared for 14 days under these conditions.
      Control animals were reared on a 12 hr light/12 hr dark cycle. Northern blotting
      of total RNA isolated from whole mouse eyes at post-natal days 7-14 (P7-P14)
      showed a marked reduction in IRBP message in the light-deprived animals to 10-20%
      of levels in control animals. Reprobing of the blots for opsin and S-antigen
      message showed a significant decrease of about 80-90% in opsin message at 5.1 kb
      but no change in S-antigen message in the eyes of light-deprived mice. Light
      microscopic examination of the light-deprived mouse retinas showed no apparent
      abnormalities in morphological development and immunocytochemistry demonstrated
      normal distribution and levels of IRBP protein. Immunochemical quantitation of
      IRBP protein confirmed that there was no reduction in light-deprived as compared
      to normal mouse eyes. Similarly, when adult mice were light-deprived for 14 days,
      a marked reduction in IRBP message was also observed with no decrease in the
      amount of IRBP protein. Thus, light deprivation causes a large decrease in IRBP
      message in the mouse eye, but IRBP protein is not decreased. The dramatic effect
      of light deprivation on IRBP mRNA and some opsin mRNAs, but not on S-antigen
      message and the fact that IRBP protein levels are relatively unaffected, suggest
      a complex pathway of light regulation of photoreceptor function previously not
      encountered. This may involve regulatory controls at levels including gene
      transcription, mRNA stability or protein degradation that may make use of a
      feedback control mechanism involving light- or dark-dependent signal
      transduction.

PMID- 8157103
TI  - Effects of dark-rearing on the retinal degeneration of the C57BL/6-mivit/mivit
      mouse.
AB  - The C57BL/6J-mivit/mivit mouse has a retinal degeneration in which photoreceptor
      cells are lost slowly at a rate of about one row per month beginning at 8 weeks.
      ROS are severely disrupted by 4 months, but inner segments maintain a normal
      length through 6 months. In addition to photoreceptor changes, the retinal
      pigment epithelium is unevenly pigmented. The present study utilized histological
      and biochemical techniques to assess the effects of dark-rearing on the
      progression of the retinal degeneration in the mivit/mivit mouse at ages 4, 6, 8,
      12, 16, 20, 24, and 28 weeks. Results of systematic morphometric evaluation
      indicated that the rate of loss of photoreceptor cells did not differ
      significantly from the rate determined for mivit/mivit animals reared in a
      standard light cycle. Furthermore, retinal detachment from RPE, the displacement
      of darkly-staining cells into the subretinal space and the influx of macrophage
      like cells in the area of the ROS were still present in mivit/mivit animals
      reared in darkness. ROS of mivit/mivit seemed to be preserved for a slightly
      longer period of time in the dark-rearing condition. Rhodopsin levels in 4-week
      dark-reared mivit/mivit mice were 0.32 +/- 0.04 nmol per retina which was
      comparable to mivit/mivit mice reared under standard lighting conditions. At 20
      and 28 weeks, rhodopsin levels decreased in mivit/mivit retinas to a similar
      level regardless of their lighting history. The findings of the study suggest
      that light deprivation does not retard the degeneration mivit/mivit retina.
      Results are discussed in comparison with effects of dark-rearing on other models
      of retinal degeneration.

PMID- 8157104
TI  - Characterization of the alpha-gamma and alpha-beta complex: evidence for an in
      vivo functional role of alpha-crystallin as a molecular chaperone.
AB  - Previous studies have demonstrated that in vitro, alpha-crystallin can protect
      other lens proteins against extensive denaturation and aggregation. The mechanism
      of this protection involves preferential binding of the partially denatured
      protein to a central region of the native alpha-crystallin complex. To test
      whether a similar phenomenon might occur in vivo, a high molecular weight
      aggregate (HMWA) fraction was isolated from the aged bovine lens. Negative
      staining of this preparation revealed the presence of particles of 13-14 nm
      diameter, characteristic of alpha-crystallin. Immunolocalization of the same
      particles using antiserum specific for gamma- and beta-crystallins demonstrated
      preferential binding of these crystallins to the central region of the alpha
      crystallin complex. Together, these results provide evidence that in the intact
      lens, the alpha-crystallins are functionally important molecular chaperones.

PMID- 8157105
TI  - Neuron-specific enolase expression during eye development in the chicken embryo.
AB  - Neuron-specific enolase has been used by others as a marker for the
      identification of cells of presumed neural crest origin in the human eye. The
      contributions of neural crest to the ocular tissues have been studied most
      definitively in the chicken embryo. The developing chicken eye was therefore
      chosen to further investigate the usefulness of neuron-specific enolase as a
      neural crest marker. Chicken embryos of various development stages were processed
      for the immunohistochemical localization of neuron-specific enolase with two
      different specific antisera. The nerve fiber layer of the neural retina and the
      optic nerve reacted positively. The first weak staining was found at day 10; it
      became rapidly stronger during the next 2 days. A positive reaction was also
      observed in the ciliary ganglion. In contrast, no staining was found in tissues
      of known neural crest origin. Cornea, sclera, trabecular tissues and iris stroma
      remained negative throughout the developmental stages studied. Therefore, neuron
      specific enolase can not be used as a reliable marker of neural crest derived
      cells, at least in the chicken embryo. Unexpectedly the lens epithelium showed
      moderate neuron-specific enolase activity beginning on day 5. alpha-Enolase is an
      important crystallin in the lens of some species, particularly the turtle. It has
      also been demonstrated to be present in the chicken lens in a fairly high
      concentration. It is possible, that neuron-specific or gamma-enolase has a
      similar role in the chicken lens.

PMID- 8157106
TI  - Nitrovasodilator effects on intraocular pressure and outflow facility in monkeys.
AB  - The nitrovasodilators nitroglycerin (NTG) and hydralazine (HZN) were investigated
      for their effects on intraocular pressure (IOP) and outflow facility in the
      cynomolgus monkey eye in vivo. Fifty microliters of 0.1% HZN were administered
      topically in masked, randomized, crossover, placebo controlled trials, and by
      intracameral perfusion. Both NTG and HZN decreased IOP (mean IOP decrease with
      NTG 4.40 +/- 2.11 (S.E.M.) (+/- 4.7, S.D.) mmHg, P < 0.01, n = 5, with HZN 3.15
      +/- 0.85 (S.E.M.) (+/- 2.3, S.D.) mmHg, P = 0.01, n = 7). Outflow facility
      increased by 92% (P < 0.05) after intracameral bolus injection of 10(-3) mol l-1
      NTG, but not at lower doses. Intracameral HZN caused a significant increase in
      facility of outflow of 28% (P < 0.05) when perfused at a constant concentration
      of 10(-5) mol l-1, but not at certain other concentrations. These results
      demonstrate the capacity for topically applied NTG and HZN to reduce IOP in the
      living primate eye. They further suggest that, at certain drug doses, but not
      others, the IOP reduction may be mediated, in part, by an action on the outflow
      apparatus.

PMID- 8157107
TI  - Plasma lipid changes in PRCD-affected and normal miniature poodles given oral
      supplements of linseed oil. Indications for the involvement of n-3 fatty acids in
      inherited retinal degenerations.
AB  - It has previously been shown that miniature poodles with progressive rod-cone
      degeneration (PRCD) have lower plasma levels of docosahexaenoic acid (22:6n-3)
      than normal poodles and it has been suggested that affected animals have a defect
      in the metabolism of 22:6n-3. To test this hypothesis in vivo, PRCD-affected and
      normal miniature poodles were given daily oral supplements of linseed oil
      (enriched in 18:3n-3). Blood was drawn from food-deprived animals at
      predetermined times before, during and after supplementation, and plasma lipid
      fatty acids were analysed. There were no differences in the levels of 18:3n-3,
      20:5n-3, and 22:5n-3 between affected and normal dogs. Therefore, there appears
      to be no abnormality in the elongation and desaturation system that takes 18:3n-3
      to 22:5n-3. Surprisingly, the plasma level of 22:6n-3 was reduced in both groups
      following supplementation, but to a significantly greater extent in affected
      dogs. This resulted in a significantly higher 22:5n-3/22:6n-3 ratio in affected
      animals. These results support the earlier suggestion of an abnormality in 22:6n
      3 metabolism in PRCD-affected miniature poodles. To determine the effect of n-3
      supplementation on polyunsaturated fatty acid metabolism in dogs (not as a
      function of disease), results from both groups of dogs were pooled and compared
      at times before and near the end of supplementation. Dietary 18:3n-3 led to
      predictable increases in 18:3n-3, 20:5n-3, and 22:5n-3, but to a decrease in
      22:6n-3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157108
TI  - Collagen-associated molecules in the cornea: localisation with monoclonal
      antibodies.
AB  - This paper describes the biochemical characteristics and immunostaining
      properties of four monoclonal antibodies (MAbs) raised to the extracellular
      matrix of bovine corneal endothelial cells in culture. All four antibodies
      labelled molecules in frozen sections of bovine cornea. MAb A15 labelled the
      collagen lamellae of the stroma. Immuno-electron microscopy located the label
      between rather than over the collagen fibrils. Antibody label was removed by
      collagenase treatment of the stroma. This antibody bound to several denatured
      collagen types in ELISAs and Western blots, the common epitope being located
      close to the collagenase binding site. A15 immunoprecipitated native polypeptides
      of 173 kDa and 150 kDa from the conditioned medium of corneal endothelial cells.
      Amino acid analysis of the 150 kDa molecule showed broad similarity to bovine
      type VI collagen although there was no immunological cross reactivity. The
      binding of this antibody in the corneal stroma may be to a collagen type VI-like
      molecule. MAb A70 bound to a collagenase sensitive molecule in corneal
      endothelial cell extracellular matrix in vitro, and to basement membranes in
      vivo. It showed staining typical of type IV collagen in frozen sections of
      cornea. MAbs A67 and A49 both labelled flexuous fibre-like structures in the
      cornea, which appeared to wrap around the fibrillar collagen lamellae. The
      molecule labelled by A67, of 86 kDa was sensitive to collagenase treatment of
      endothelial cell conditioned medium, yet totally resistant to collagenase
      treatment of the cornea, which completely removed the fibrillar collagen from the
      stroma. In the endothelial extracellular matrix, this antigen was resistant to
      all proteases tested and required severe denaturing conditions to remove
      antigenic activity. Amino acid analysis did not yield the high proportion of
      glycine typical of collagens, so if collagenous sequences occur they must be
      relatively short. The molecule labelled by A49 was a 51-kDa protein, of similar
      amino acid composition to antigen 67, and showed a similar distribution in frozen
      sections of bovine cornea. There was, however, no immunological cross reactivity
      between the two. Unlike antigen 67, antigen 49 was not sensitive to collagenase
      under any conditions and was very sensitive to protease treatment of the
      endothelial extracellular matrix. Immuno-electron microscopy showed labelling
      with both these antibodies between the collagen fibrils in the stroma. We
      postulate that these two molecules may be involved in stabilising the lamella
      structure of the corneal stroma.

PMID- 8157109
TI  - Axial intensity distribution analysis of the human retina with a confocal
      scanning laser tomograph.
AB  - We have analysed the change of reflected light intensity along the optical axis
      or axial intensity distribution in images acquired with a confocal scanning laser
      tomographic system in human fundus examination. We hypothesized that confocal
      light detection units used in scanning laser tomographs register light
      originating from multiple layers within the human macula and that intraretinal
      structures might also be observable. To test this hypothesis we examined the
      axial intensity distribution in human maculas of normal volunteers, patients with
      cystic and other macular abnormalities and in an artificial retina in a plastic
      eye model. A total of over 140 patients and volunteers were examined. We analysed
      this distribution in 20 normal healthy volunteer eyes found the origin of the
      artifacts that cause retinal vessels to appear elevated. We examined four
      patients with cystic maculas and were able to detect the presence of two
      structures in axial direction contributing to the axial intensity distribution. A
      plastic eye model with a cellophane sheet covering a fluid pocket was developed
      to mimic the appearance of a large macular cyst. The axial intensity distribution
      analysis showed the presence of two distinct gaussian profiles. The results of
      this study show that confocal scanning laser tomographic imaging of the human
      fundus allows extraction of information regarding the axial position of
      intraretinal layers and that correction for the deeper retinal reflections may
      allow more precision in imaging of the retinal surface.

PMID- 8157110
TI  - Identification of type VI collagen in the trabecular meshwork and expression of
      its mRNA by trabecular cells.
AB  - To investigate the nature of the 140 kDa glycoprotein in the trabecular meshwork,
      polypeptides were extracted with either urea/sodium dodecyl sulfate (SDS)/beta-2
      mercaptoethanol (BME) or guanidine hydrochloride followed by pepsin digestion.
      After electrophoresis and immunoblotting with anti-type-VI-collagen antibodies, a
      single fraction of molecular weight 140 kDa was identified in the urea/SDS/BME
      extracts. Pepsin solubilization revealed two immunoreactive fractions (molecular
      weights 75 and 85 kDa) that comigrated with purified, pepsin-solubilized type VI
      collagen. By using the polymerase chain reaction (PCR) and primers specific for
      the alpha 2(VI) chain of type VI collagen, a single PCR product was obtained,
      which corresponded to the expected size of 137 base pairs, from the total RNA
      extracted from the trabecular meshwork ex vivo. Southern hybridization with the
      antisense oligonucleotide probe of the alpha 2(VI) chain confirmed that the
      amplified sequence was specific. The results show that the trabecular meshwork
      contains a significant amount of type VI collagen and that trabecular cells
      express the mRNA coding for the alpha 2(VI) chain of this glycoprotein. The
      presence of type VI collagen in the trabecular meshwork is implicated in cell
      extracellular matrix interactions at this site, and its abnormal accumulation in
      glaucomatous and aging eyes probably signifies a defect in the function of the
      trabecular cells in these eyes.

PMID- 8157111
TI  - Actin filament bundles are associated with fiber gap junctions in the primate
      lens.
AB  - A unique association between actin filament bundles and gap junctions in cortical
      fiber cells of human and monkey lenses was studied with thin-section electron
      microscopy and immunocytochemistry. Thin-section electron microscopy showed that
      distinct layers of filament bundles (approximately 55 nm thick) were consistently
      associated with fiber gap junctions (approximately 16 nm thick) from intermediate
      to deep cortical regions in both species studied. The filament bundle was
      composed of 6-8 nm microfilaments which lay along both cytoplasmic surfaces of
      the junction. Fluorescence microscopy revealed a patchy pattern of F-actin
      labeling along the fiber cell membranes in the intermediate and deep cortical
      regions of the lens. The size and distribution pattern of F-actin labeling appear
      to correlate well with those of filament bundles/gap junctions seen in thin
      section electron microscopy. By immunoelectron microscopy, the anti-actin
      antibody was shown to be localized to filament bundles/gap junctions in the
      intermediate cortical fibers of human lens, indicating that filament bundles are
      F-actin in nature. The identical filament bundle/gap junction association was not
      found in other species examined, including rodent, bird and fish, by the same
      procedure, suggesting that an association between actin bundles and gap junctions
      has a special functional role in the primate lens. It is proposed that gap
      junction-associated actin bundles may provide added structural stability for the
      primate lens.

PMID- 8157112
TI  - Dihydropyridine-sensitive Ca2+ spikes and Ca2+ currents in rabbit ciliary body
      epithelial cells.
AB  - Intracellular microelectrode and whole-cell patch-clamp recordings were used to
      investigate a Ba(2+)-induced regenerative depolarization and its underlying Ba2+
      current in the ciliary body epithelial cells of the rabbit eye. Exposure of these
      epithelial cells to 4-10 mmol l-1 Ba2+ depolarized the membrane potential and
      caused the generation of one or more spikes, before the membrane potential
      reached a steady-state level. The spikes, but not the slow phase of
      depolarization, could be blocked with Co2+ (2 mmol l-1), Gd3+ (25 mumol l-1),
      La3+ (20 mumol l-1), Cd2+ (10 mumol l-1), verapamil (30 mumol l-1) and nifedipine
      (1 mumol l-1). Tetrodotoxin at 100 nmol l-1 had no effect. In the absence of Na+,
      but in the presence of external Ba2+, step depolarization of the membrane
      potential activated an inward current that could be blocked with Co2+ (2 mmol l
      1), Cd2+ (10 mumol l-1) and nifedipine (1 mumol l-1), but not with Ni2+ (50 mumol
      l-1) or omega-conotoxin (1-10 mumol). This inward current could be enhanced with
      the dihydropyridine agonist (+/-)BAY K 8644 (1 mumol l-1). The inactivation
      characteristics of the inward current (v1/2 = -38.7 mV, k = 12.6 mV) is most like
      that seen in neurons. These findings indicate that the epithelial cells of the
      ciliary body possess dihydropyridine-sensitive, voltage-activated Ca2+ channels.

PMID- 8157113
TI  - A physiological level of ascorbate inhibits galactose cataract in guinea pigs by
      decreasing polyol accumulation in the lens epithelium: a dehydroascorbate-linked
      mechanism.
AB  - It was reported previously that dietary ascorbate (ASC) delays the development of
      galactose-induced cataract in guinea pigs compared to the rate which is observed
      in ASC-deficient animals. Experiments were conducted to explore the possible
      mechanism of this phenomenon. Guinea pigs were fed for a period of up to 4 weeks
      either a normal diet (1 g ASC/kg diet) or a scorbutic diet (< 0.04 g ASC/kg diet)
      combined with 10% galactose in the drinking water. After 2 weeks, levels of ASC
      in animals on the scorbutic diet decreased by 95% in the aqueous humor and by 78%
      in the lens. Slit lamp examination showed that galactose-induced vacuoles in the
      lens equator formed at a significantly faster rate in the scorbutic animals.
      However, examination of biochemical parameters in whole lenses of the two groups
      of animals after 2 weeks showed no significant differences with regard to
      accumulation of galactose and galactitol, decreases in the levels of myoinositol,
      taurine and GSH or changes in cation concentrations. In order to examine possible
      regional changes in the lenses, various parameters were studied in the lens
      capsule-epithelium. On day 4, the capsule epithelia of scorbutic animals on a
      galactose diet had a content of galactitol two-and-a-half times higher than that
      of normal galactose-fed animals. Scorbutic conditions also intensified the loss
      of Na(+)-K+ ATPase activity in the lens capsule-epithelium caused by galactose
      feeding. Oxidized glutathione was not detectable in the lens capsule epithelia of
      any of the animals studied. Hexose monophosphate shunt activity was elevated in
      lenses of normal galactose-fed animals during the first hour of culture after
      death whereas lenses of scorbutic galactose-fed animals were not. Consistent with
      the in vivo findings, galactitol accumulation in dog lens epithelial cells
      exposed to 30 mM galactose was significantly inhibited by the presence of either
      ASC or dehydroascorbate (DHA) in the medium. Hexose monophosphate shunt activity
      in the cells was stimulated to two-and-a-half times its initial level by either 1
      mM DHA or 30 mM galactose and slightly more than three-fold by a combination of
      the two challenges. The results suggest that decreased polyol accumulation in the
      lens epithelium of the normal galactose-fed guinea pig, which has a high level of
      ASC in the aqueous humor, accounts for the delay in onset of cataract compared to
      that for the ASC-deficient animal.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8157114
TI  - Hydration of gamma-crystallins.
AB  - Four fractions of gamma-crystallins, B(II), C(IIIb), D(IIIa) and E(IVa), were
      isolated from bovine lenses. The hydration properties of each fraction were
      measured as a function of protein concentration. The freezable water content was
      obtained by differential scanning calorimetry and the total water content by
      thermogravimetric analysis. The difference yields the non-freezable (bound) water
      content of the crystallins. At physiological protein concentrations the order of
      the bound water content was C(IIIb) > D(IIIa) >> E(IVa) > B(II). This order was
      reversed between C and D and between B and E at low protein concentrations. This
      trend was evident whether the bound water was calculated as a percentage of the
      total water or as quantity per gram of gamma-crystallin.

PMID- 8157115
TI  - Selenite-induced damage to lens membranes.
AB  - The present study focuses on three aspects of membrane damage to explain selenite
      induced loss of ion homeostasis: membrane transport processes, i.e. cation pump;
      biosynthesis of membrane proteins and membrane permeability. Cation pump
      activity, assessed by both 86Rb uptake and Na-K-ATPase activity in the
      epithelium, was observed to decline gradually after exposure to selenite and
      subsequent culture for 2 days in a selenite-free medium. In fact, the major loss
      of transport and ATPase activity occurred during culture of lenses after transfer
      from selenite to a selenite-free medium. The delay between selenite presentation
      to the lens and final inhibition of the cation pump (47%) corresponds to the
      delay in the observed loss of Na-K-ATPase activity (50%). Initial loss of cation
      transport and Na-K-ATPase activity may be due to the oxidative capacity of
      selenite. Oxidation, however, might not explain the delayed, progressive loss of
      transport activity after selenite removal. A plausible cause for this sustained
      loss might be a depleted supply of Na-K-ATPase due to impaired biosynthesis.
      Evidence for such a possibility comes from the observation that the rate of
      synthesis of total membrane protein is impaired by 44% in selenite-treated
      lenses. Membrane permeability to Na+ was not affected at the end of day 1, a
      conclusion based on the following observation: ouabain-treated lenses exposed to
      selenite did not gain any more Na+ than did ouabain-treated lenses. With the pump
      blocked by ouabain in both groups of lenses, the passive influx of Na+ was
      unchanged by selenite, indicating little damage to membrane
      permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157116
TI  - Sulfated proteoglycans in the lamina cribrosa of normal monkey eyes and monkey
      eyes with laser-induced glaucoma.
AB  - The distribution of the sulfated proteoglycans in the lamina cribrosa of normal
      monkey eyes and monkey eyes with laser-induced glaucoma were analysed by electron
      microscopy after cuprolinic blue dye binding. Three types of cuprolinic blue
      positive filaments, CB-1, CB-2 and CB-3, were identified in the laminar beams of
      normal monkey eyes. CB-1 and CB-2 were both small filaments representing
      chondroitin and dermatan sulfate proteoglycan copolymers. The former lined up
      perpendicularly to the long axis of collagen fibrils, whereas the latter ran
      axially parallel to collagen fibrils. The large CB-3 filaments, representing
      chondrotin sulfate proteoglycans, were located around collagen bundles or in
      loose spaces within the beams. In addition, small CB-4 filaments or punctate
      structures representing heparan sulfate proteoglycans were found aligned on the
      basal laminae of blood vessels and glial cells. In the glaucomatous eyes,
      accumulation and enlargement of collagen-associated proteoglycan filaments were
      seen, accompanied by the destruction of collagenous beams. Accumulation of
      chondroitin sulfate proteoglycans was most evident. Prominent filamentous heparan
      sulfate/heparin proteoglycans were also noted in thickened astrocytic and
      vascular basal laminae. These may be alterations secondary to the destruction of
      collagen bundles. They may also represent cellular responses related to
      intraocular pressure elevation.

PMID- 8157117
TI  - Altered retinal recovery and optic nerve fiber loss in primary open-angle
      glaucoma in the beagle.

PMID- 8157118
TI  - Presence of immunoreactive blue cones in the fetal monkey fovea.

PMID- 8157119
TI  - Fibroblasts genetically modified to produce nerve growth factor induce robust
      neuritic ingrowth after grafting to the spinal cord.
AB  - The influences of neurotrophic factors on adult mammalian spinal cords are
      incompletely understood. In the present experiment, we utilized somatic gene
      transfer to examine the effects of nerve growth factor (NGF) on the unlesioned
      spinal cords of adult Fischer rats. Fischer 344 rat primary fibroblasts were
      genetically modified in vitro to produce and secrete NGF, then grafted to spinal
      cords at the T7 level. Grafts survived in vivo for periods of up to 1 year, and
      induced an extremely robust ingrowth of spinal neurites. Control and basic
      fibroblast growth factor-producing grafts did not promote extensive neurite
      growth. Neurites penetrating the NGF grafts were of sensory origin, since they
      labeled immunocytochemically for calcitonin gene-related peptide but not markers
      of other neuronal transmitter phenotypes. Electron microscopy revealed that
      neurites within NGF-secreting grafts were enveloped in glial cell processes and
      that axons frequently became myelinated. These results indicate that (i)
      genetically modified cell grafts are a useful model for studying trophic factor
      effects in the adult mammalian spinal cord, (ii) sensory neurites maintain robust
      NGF responsiveness into adulthood, and (iii) sprouting neurites can follow glial
      channels and become myelinated in the adult spinal cord. Grafts of fibroblasts
      genetically modified to secrete trophic factors merit study as potential tools
      for promoting regeneration after spinal cord injury.

PMID- 8157120
TI  - Quisqualate injection into the nucleus basalis magnocellularis produces seizure
      related brain damage that is prevented by MK-801.
AB  - Quisqualate (Quis) and other excitotoxins such as ibotenate and N-methyl
      aspartate, have been used to destroy neurons in the area of the nucleus basalis
      magnocellularis (NBM) in order to study the relationship between loss of
      cholinergic neurons in the basal forebrain and various behavioral deficits,
      including learning and memory impairments. The results of several studies suggest
      that although Quis NBM lesions may produce greater depletions in cortical choline
      acetyltransferase levels than ibotenate lesions, the learning/memory deficits
      tend to be milder following Quis lesions. In these studies, it was often assumed
      that the lesions induced by Quis were restricted to the local vicinity of the
      injection. However, in the present study, we found that an injection of Quis into
      the NBM/substantia inominata (SI) region often induces limbic seizures and
      disseminated brain damage. Specifically, we found that an injection of Quis into
      the NBM/SI area of female rats at a dose (120 nmol) used by others in previous
      behavioral studies produced massive damage in areas distant from the lesion site,
      particularly in the amygdala and piriform cortex. This disseminated damage
      occurred in 50% of the rats treated with Quis, was typically more severe than
      damage at the injection site, and was often accompanied by equally severe
      "mirror" lesions in the contralateral amygdala and piriform cortex. Injecting
      rats with MK-801 (1 mg/kg) 30 min before the Quis injection protected against the
      disseminated damage. These data underscore the need for careful histological
      evaluation of excitotoxic lesions and for caution in interpreting the
      relationship between altered transmitter markers and learning/memory impairment
      seen following these lesions.

PMID- 8157121
TI  - Hypoxic-ischemic brain injury stimulates glial fibrillary acidic protein mRNA and
      protein expression in neonatal rats.
AB  - Accumulation of glial fibrillary acidic protein xk(G-FAP) in reactive astrocytes
      is a characteristic neuropathologic feature of ischemic brain injury. We examined
      injury-induced changes in GFAP mRNA and protein in a well-characterized model of
      focal hypoxic-ischemic injury in perinatal rodent brain. Postnatal Day (PND) 7
      rats underwent right carotid artery ligation followed by 2.5 h exposure to 8%
      oxygen, which results in injury to ipsilateral cortex, hippocampus, and striatum
      in the majority of animals. Using Northern analysis, we assayed GFAP mRNA in
      samples from the lesioned and contralateral hemispheres of animals killed 1 h to
      14 days later, and from animals treated with the neuroprotective glutamate
      antagonist MK-801. GFAP immunoreactivity in tissue homogenates from the lesioned
      and contralateral hemispheres was also compared with an immunoblot assay. One and
      4 h posthypoxia GFAP mRNA expression was barely detectable. In the lesioned
      cortex, increased GFAP mRNA was detected at 24 h postinjury; over the next 2
      weeks GFAP mRNA was consistently higher (at least 2-fold) in lesioned than in
      contralateral cortex. In contrast, in lesioned hippocampus and striatum,
      consistent increases in GFAP mRNA were first detected on PND 12. Immunoassays of
      GFAP demonstrated early (PND 8) and sustained (to PND 21) up to 10-fold increases
      in lesioned cortex, hippocampus, and striatum. In this perinatal stroke model
      regionally specific increases in GFAP mRNA expression and GFAP immunoreactivity
      are detected in the first 2 weeks after hypoxic-ischemic injury; intrinsic
      properties of glia and/or neurons in different brain regions may influence the
      timing and magnitude of stimulation of this response.

PMID- 8157122
TI  - Age-related changes in activities and localizations of cathepsins D, E, B, and L
      in the rat brain tissues.
AB  - Altered cellular levels and localizations of four distinct intracellular
      proteinases, cathepsins D, E, B, and L, with aging were studied in various rat
      brain tissues by enzymatic and immunohistochemical methods using discriminative
      antibodies specific for each enzyme. With regard to two aspartic proteinases,
      cathepsin E was barely detectable in all the brain tissues of young adult rats,
      including the cerebral cortex, the hippocampus, the neostriatum, and the
      cerebellum, whereas cathepsin D was ubiquitously found in these tissues. Two
      cysteine proteinases, cathepsins B and L, also existed in these tissues of young
      rats at the relatively high levels of activities. In aged rats, the cathepsin D
      levels in all of the brain tissues examined were about twice those of young rats.
      Cathepsin E was markedly increased in the cerebral cortex and neostriatum of aged
      rats, but not in the other tissues. The levels of cathepsin B were also increased
      significantly in the neostriatum of aged rats, but not significantly in the other
      tissues. In contrast, the activity levels of cathepsin L were strikingly
      decreased in all the brain tissues of aged rats. At the light microscopic level,
      the increased immunoreactivity of cathepsins D and E in the brain tissues of aged
      rats was eminent in both the neurons and the glial cells. By double
      immunostaining technique, the cathepsin D-positive glial cells were mainly
      associated with reactive astrocytes, whereas the cathepsin E-positive glial cells
      were largely reactive microglial cells. Western blot analyses revealed that the
      molecular forms of cathepsins D and E increasingly expressed in the cerebral
      cortex of aged rats were similar to those of the respective normal mature
      enzymes. The increased immunoreactivity of cathepsin B in the neostriatum of aged
      rats was also found in both the neurons and the glial cells. Despite the marked
      decrease of the cathepsin L activity in various brain tissues of aged rats, the
      immunostaining for this enzyme was not significantly changed, indicating the
      occurrence of the catalytically inactive form of the enzyme in these tissues.
      These results suggest that the increased levels of cathepsins D, E, and B and the
      decrease in cathepsin L activity in brain regions of aged rats are related to
      both the neuronal degeneration and the reactivation of glial cells during the
      normal aging process of the brain.

PMID- 8157123
TI  - Essential tremor entrains rapid voluntary movements.
AB  - The effect of essential tremor on the timing of rapid wrist flexion was examined
      in 10 patients with moderate to severe disability. The mean reaction time and
      motor time of the patients did not differ from the mean values of 10 healthy age-
      and sex-matched controls. The latencies of the triphasic agonist and antagonist
      EMG bursts did not differ between patients and controls. The initiation of
      movement was time-locked to the tremor cycle in all patients. The initial agonist
      muscle activation occurred in phase with the rhythmic bursts of EMG, but the
      onset of rapid wrist flexion occurred when the momentum of essential tremor
      opposed the volitional movement. Essential tremor has subtle effects on motor
      control that transcend oscillation per se. These effects probably contribute to
      the impaired performance of fine motor tasks in patients with advanced disease.

PMID- 8157124
TI  - Axotomy-induced changes in ribosomal RNA levels in female hamster facial
      motoneurons: differential effects of gender and androgen exposure.
AB  - Following facial nerve injury, female hamster facial motoneurons (HFMN)
      regenerate faster than their male counterparts. Testosterone propionate (TP)
      markedly accelerates the rate of facial nerve regeneration in males, but has a
      relatively reduced effect in females. In the present study, we utilized in situ
      hybridization in conjunction with ribosomal DNA probes to test the hypothesis
      that in females HFMN axotomy produces a less dramatic cell body response than in
      males and to examine gender differences in the effects of steroids on peripheral
      nerve regeneration at the molecular level. The results indicate that in females
      axotomy alone induced moderate increases in rRNA levels, beginning 2 days
      postoperatively. These changes were both slower in onset and lower in magnitude
      than those in the males. TP augmented the effects of axotomy on rRNA levels at
      the later postoperative times. There were no early, rapid effects of TP, like
      those observed in males. These molecular data substantiate our previous findings
      of inherent sex differences in neuronal regeneration and the ability of gonadal
      steroids to augment the reparative response of peripheral neurons to injury.

PMID- 8157125
TI  - Extrusion transplantation of Schwann cells into the adult rat thalamus induces
      directional host axon growth.
AB  - In a previous study we found that Schwann cells microtransplanted into the
      central nervous system rapidly dispersed from the transplantation site and became
      intimately associated with host grey and white matter. We have now investigated
      whether this migratory behavior of the donor Schwann cells is compatible with the
      production of stable, continuous anatomical cell tracks and whether such tracks
      can induce directional host axon growth. During the gradual withdrawal of a
      micropipette, highly purified suspensions of cultured adult peripheral nerve
      Schwann cells were continuously extruded to form a vertical column of cells
      extending for up to 4 mm through the thalamus and across the choroid fissure into
      the hippocampus of adult rat hosts. The donor Schwann cells were identified by
      immunohistochemistry for low-affinity nerve growth factor receptor, vimentin, and
      Rat 401. Although donor Schwann cells migrated into the host tissues, a large
      number remained along the axis of the injection track to form a column which was
      maintained for up to 3 weeks. From 4 days, increasing numbers of parallel,
      unbranching host RT97-positive axons entered the Schwann cell column in alignment
      with the long axis of the Schwann cells in the vertical tracks. The axons did not
      fasciculate directly with each other, but mingled diffusely with the Schwann
      cells. The Schwann cell tracks were able to convey host axons out of the dorsal
      thalamus, across the extracellular space of the choroid fissure, and into the
      ventral hippocampus. Thus, Schwann cells, transplanted in the form of elongated
      tracks, can establish bridges across boundary membranes in the brain and carry
      substantial numbers of nerve fibers from one area to another.

PMID- 8157126
TI  - The astrocyte inhibition of peripheral nerve regeneration is reversed by Schwann
      cells.
AB  - Schwann cell transplantation into the lesioned or demyelinated central nervous
      system (CNS) is being extensively explored as an approach to favorably
      influencing repair in the CNS. Under a variety of circumstances, however, the CNS
      glial microenvironment appears to offer an unfavorable terrain for the promotion
      of neurite elongation and for Schwann cell differentiation. Due to the
      heterogeneity of the cellular contents at injury sites, the specific role of each
      cell type present in limiting Schwann cell function is unclear. The damaged
      peripheral nervous system, a system capable of substantial regeneration (and free
      of the potentially negative influence of oligodendrocytes), represents a valuable
      model in which to specifically evaluate the influence of astrocytes on Schwann
      cell function. In the present study, purified cortical astrocyte populations were
      seeded into semipermeable guidance channels alone or in combination with adult
      Schwann cell populations to determine their effects on regeneration across an 8
      mm gap in the transected sciatic nerve of the adult rat. Channels were prepared
      with (or without) a defined cellular content, implanted in inbred Lewis rats and
      evaluated after 3 weeks. Channels seeded with astrocytes alone impeded
      regeneration, regardless of the maturity of the astrocytes (7-8 days vs 28 days
      in culture) and their seeding density (40 vs 80 x 10(6) cells/ml). On the other
      hand, Schwann cells derived from adult sciatic nerve seeded at similar densities
      enhanced the regenerative process. Regenerative capacity was diminished when
      astrocytes were combined with Schwann cells; the rate of regeneration increased
      as the number of Schwann cells in the astrocyte/Schwann cell mixture increased.
      Immunostaining of the nerve stumps related to astrocyte-seeded channels and of
      the regenerated tissue in the astrocyte-Schwann cell-seeded channels indicated
      that astrocytes had migrated into the proximal nerve stump; only a few astrocytes
      remained within the regenerated cable. The present experiments show that although
      astrocytes alone inhibit nerve regeneration, Schwann cells are able to partially
      overcome this inhibition if they are provided in sufficient numbers. We believe
      these observations will be valuable in considering clinical strategies to use
      autologous Schwann cell transplantation to influence CNS regeneration.

PMID- 8157127
TI  - Modeling of acute spinal cord injury in the rat: neuroprotection and enhanced
      recovery with methylprednisolone, U-74006F and YM-14673.
AB  - We used a new injury device that produces consistent spinal cord contusion
      injuries (T8) in rats to compare the behavioral and histologic effects of
      methylprednisolone sodium succinate (MPSS) administration, the clinical standard
      of therapy after acute spinal cord injury (ASCI), with the 21-aminosteroid, U
      74006F (U74), and the TRH analogue, YM-14673 (YM), at different trauma doses.
      Three sequential experiments were conducted: Experiment 1. U74 (3.0/1.5/1.5
      mg/kg; 10/5/5 mg/kg; 30/15/15 mg/kg), MPSS (30/15/15 mg/kg), or vehicle were
      administered intravenously (i.v.) at 5 min, 2 and 6 h after the injury (n =
      8/group). U74 (10/5/5 mg/kg) and MPSS animals scored better than controls (Days 8
      43) in open field walking (OFW); no other differences were seen between groups.
      Experiment 2. Dose-response evaluation of MPSS determined more effective doses.
      Groups (n = 16) receiving 30/30/30/30 mg/kg and 60/60/60/60 mg/kg i.v. at 5 min
      and 2, 4, and 6 h after the injury had better OFW scores than controls (Days 8
      29; Day 29). Both groups performed better than controls (Days 8-29) on inclined
      plane (IP); 30 mg/kg animals scored higher on Day 29. Percentage tissue spared
      (%TS) at the lesion center was greater for 60 mg/kg animals (23.4%) than controls
      (17.3%). Experiment 3. Compounds were administered as in experiment 2 (n =
      15/group); MPSS (60/30/30/30 mg/kg) and YM (1/1/1/1 mg/kg and 1 mg/kg/day ip)
      were most effective. YM and MPSS combination produced no additive effects. YM
      animals scored better than MPSS and control animals in OFW (Days 8-29) and better
      than controls on IP (Days 8-29; Day 29) and grid walking (Day 29). MPSS animals
      scored better than controls on IP (Days 8-29). YM and MPSS groups had greater %TS
      than controls. This series of experiments demonstrates the utility of this injury
      model and simple behavioral measures for preclinical assessment of pharmacologic
      agents. Under these experimental conditions, U74 demonstrated equivalent efficacy
      to MPSS, and YM demonstrated greater efficacy than MPSS in the treatment of ASCI.

PMID- 8157128
TI  - Spinal cord injury in the rat: treatment with bacterial lipopolysaccharide and
      indomethacin enhances cellular repair and locomotor function.
AB  - Trauma to the rat's spinal cord results in a lesion characterized by ingrowth of
      glial cells, accumulation of macrophages, and the progressive development of
      necrosis and cavitation. Since, when appropriately activated, both astrocytes and
      macrophages secrete growth-promoting cytokines, we examined whether treatment
      with drugs that stimulate the secretory activities of these cells might promote
      tissue repair and reduce necrosis in the traumatized spinal cord. The spinal cord
      of rats was crushed extradurally at T8 and the rats were injected
      intraperitoneally with (i) a lipopolysaccharide (LPS) or ImuVert to activate
      cytokine secretion, (ii) Indomethacin to reduce necrosis by inhibiting
      prostaglandin synthesis, (iii) a combination of LPS+Indomethacin, or (iv)
      vehicle. After 28 days the lesion site was examined quantitatively by light
      microscopical image analysis. The lesion of vehicle-treated control animals
      showed large cavities, extensive infiltration by debris-engorged macrophages, and
      relatively few axons. Treatment with LPS or ImuVert significantly reduced the
      degree of cavitation and increased the number of cells and axons in the lesion.
      Treatment with LPS+Indomethacin was significantly more effective than treatment
      with LPS alone, while treatment with Indomethacin alone was ineffective. To test
      whether the histopathological differences between treated and control rats might
      be reflected in functional improvement, rats were subjected to a contusion
      (weight-drop) injury and their walking ability was quantified by the Tarlov scale
      for 28 days postoperatively. Treatment with LPS+Indomethacin significantly
      improved locomotor function of animals subjected to a moderate (1.25 g x 20 cm)
      injury. We conclude that tissue repair and functional recovery after spinal cord
      injury are enhanced by combined treatment with agents that promote the secretory
      activities of the nonneuronal cells and that inhibit prostaglandin synthesis.
      These results indicate that the search for more effective treatments should
      include studies on combinations of drugs having different pharmacological
      specificities.

PMID- 8157129
TI  - Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of
      rabbits with dietary cholesterol.
AB  - beta-amyloid and ALZ-50 immunocytochemical reactivity were determined in the
      brains of rabbits fed either a control or 2% cholesterol diet. Control rabbits
      demonstrated no accumulation of intracellular immunolabeled beta-amyloid within 3
      min after death. In animals fed the experimental diet for 4, 6, and 8 weeks
      (postmortem interval < 3 min), there was an increasingly mild-to-moderate-to
      severe accumulation of intracellular immunolabeled beta-amyloid. Whether or not
      beta-amyloid is causally linked to processes leading to dementia, it is related
      in some way to the prime cause of human death; heart disease.
      Hypercholesterolemic rabbits may provide an animal model to study altered beta
      APP metabolism leading to Alzheimer-like beta-amyloid accumulation xe03and
      extracellular deposition in brain.

PMID- 8157130
TI  - GM1 ganglioside treatment of spontaneously hypertensive stroke prone rats.
AB  - Many reports indicate that GM1 ganglioside is effective in reducing CNS ischemic
      injury in animal models. These models employ invasive surgery to induce ischemic
      damage in otherwise healthy animals. The purpose of this study was to determine
      if the beneficial effects of GM1 could be generalized to Spontaneously
      Hypertensive Rats-Stroke Prone (SHRSP). The SHRSP strain develops a pathology
      similar to those observed in patients with stroke. The SHRSP have "risk" factors
      that include hypertension, fibrinoid necrosis, and sensitivity to diet. Female
      SHRSP were randomly assigned to GM1- or saline-treatment conditions. Rats were
      fed a stroke-inducing diet. Daily body weights, weekly blood pressure, time of
      stroke onset, and age at death were recorded. Spontaneous activity and
      performance on a tail-hang test were assessed thrice weekly. The results indicate
      that GM1 treatment did not delay the time of stroke onset or death. GM1 did
      reduce hyperactivity in the initial stages of the ischemic pathology, but did not
      prevent the marked decline in behavioral activity observed at later time points.
      There were no differences in weight loss, performance on the tail-hang test, or
      number of CNS injury-related symptoms observed. These findings suggest that GM1
      was not as effective in decreasing mortality, weight loss, or behavioral deficits
      in SHRSP as previously reported using other animal models of ischemia.
      Distinguishing between those animal models in which GM1 is more and less
      effective may be useful in determining under which clinical situations GM1 is
      likely to be most suitable.

PMID- 8157131
TI  - Genetic polymorphism of factor B (Bf) and C3 component of complement in type 1
      (insulin-dependent) diabetes mellitus: BFQO allele observed in a diabetic child.
AB  - C3 and Bf polymorphisms were studied in 215 and 192 children with type 1 diabetes
      mellitus (IDDM), respectively. No significant differences in C3 phenotypes and
      allele frequencies were found between IDDM patients and a healthy population. The
      rare allele BfF1 was found in 9.37% of diabetic patients but in only 0.35% of the
      general Slovak population (0.0468 vs. 0.0017). An increased frequency rate of
      BfSO.7 was also observed in 8.85% of IDDM patients compared with 3.57% of healthy
      controls (0.0442 vs. 0.0178). The relative risk was 28.83 for BfF1 and 2.55 for
      BfSO.7. One diabetic child was found to be heterozygous for a silent allele BfQO.
      This rare Bf allele was transmitted to the boy from his healthy mother.

PMID- 8157132
TI  - Expression of CDw12 and CD17 cell surface antigens on leukemic cells from
      patients with blood malignancies.
AB  - In 67 cases of newly diagnosed blood malignancies, NonT-ALL, T-ALL, AMLL, AML,
      CML, CLL, HCL, PLL, MDS, B splenic lymphoma, AUL, as well as in 9 cell lines
      (U937, HEL, Jurkat, HL60, UHKT2, KG1, Raji, K562, REH), we have analysed the
      expression and distribution of 2 relatively incompletely studied antigenic
      markers from the CD nomenclature: CDw12 and CD17, individually and in combination
      with well characterized ones. We present our data for the usefulness of these
      molecules in immunodiagnosis of leukemias and lymphomas.

PMID- 8157133
TI  - Dynamics of mitotic activity and expression of viral proteins gp51 and p24 of
      bovine leukemia virus producing cells.
AB  - The dynamics of expression of viral proteins gp51 and p24, virus particle
      production and mitotic activity of a highly productive bovine leukemia virus
      clone of the fetal lamb kidney (FLK) cell line were studied. The period of the
      highest protein production (20-44 h after incubation) was established by the
      indirect immunofluorescence method using specific monoclonal antibodies. It was
      followed by a complete formation of the cell monolayer and the most intensive
      period of the mitotic activity determined by the 3H-thymidine labeling method.
      After the active synthesis of viral protein, the formation of mature viral
      particles and their shedding in the intercellular spaces was established electron
      microscopically and by the syncytia induction test. A similar comparative study
      was carried out with a BLV producing short-term lymphocyte culture (STLC).

PMID- 8157134
TI  - Cytostatic effect of 9-(2-phosphonomethoxyethyl) adenine (PMEA). I. Lymphatic
      leukemia KHP-Lw-I in Lewis rats.
AB  - PMEA was administered i.p. daily on 10 consecutive days to inbred LEW rats
      inoculated with leukemic lymphoblastic cells KPH-Lw-I. The treatment was started
      24 h after the inoculation. The observed cytostatic effects consisted in a
      significant prolongation of survival time associated with a suppression of the
      number of bone marrow leukemia cells with characteristic chromosomal marker of
      KPH-Lw-I leukemia as well as with a depression of the number of lymphoblasts in
      the blood.

PMID- 8157135
TI  - Cytostatic effect of 9-(2-phosphonomethoxyethyl) adenine (PMEA). II.
      Lymphoblastic leukemia in Sprague-Dawley rats.
AB  - Two cases of spontaneous acute lymphoblastic leukemia in the inbred strain of
      Sprague-Dawley (Prague) rats have been observed. Since its reliable
      transplantability in syngeneic recipients was established, leukemic animals were
      used to test the cytostatic effect of PMEA. The treatment resulted in a
      significant prolongation of survival time of the treated animals. At the same
      time histological examination of PMEA-treated and untreated animals indicated
      that the drug effectively slows down the growth of lymphoma at the site of
      inoculation and inhibits the subsequent progression of tumor cells in the lung,
      liver, spleen and lymph nodes.

PMID- 8157137
TI  - Antimicrobial activity and immunological side effects of different antibiotics.
AB  - Antibiotics, in addition to killing or inhibiting the growth of microorganisms,
      may also affect the immune response in many ways. Such effects may be clinically
      relevant especially when an impairment of immunological functions is seen. This
      study was designed to analyse the influence of various groups of antibiotics on
      the host defence system by using different tests in vitro on human or animal
      cells and in vivo on an animal model. At the same time we analysed the
      antimicrobial effectiveness of the same antibiotics on over 2800 bacterial
      strains isolated from our clinical material. Preliminary findings show that a
      correlation exists between the effect of antibiotics on the immune response,
      especially the humoral response, and the appearance of resistance in bacteria to
      these antibiotics.

PMID- 8157136
TI  - Antimitotic and teratogenic effects of acyclic nucleotide analogues 1-(S)-(3
      hydroxy-2-phosphonomethoxyethyl)cytosine (HPMPC) and 9-(2-phosphonomethoxyethyl)
      adenine (PMEA).
AB  - The acyclic nucleotide analogues, HPMPC and PMEA, differ in their in vitro effect
      on the genetic material of eukaryotic cells. While HPMPC exerts a cytostatic
      effect on eukaryotic cells in vitro, PMEA has a genotoxic activity. These results
      correspond with the mode of embryotoxic action of these compounds: HPMPC exhibits
      a general embryolethal effect, whereas PMEA is apparently teratogenic and
      interacts with the mutant allele producing preaxial polydactyly of the hind
      limbs.

PMID- 8157138
TI  - Immunoreactive inhibin-production in post-menopausal women with malignant
      epithelial ovarian tumors.
AB  - In post-menopausal women with a malignant epithelial ovarian tumor the follicle
      stimulating hormone (FSH) level was found to be significantly lower compared with
      healthy controls. We demonstrated immunoreactive (i.r.) inhibin in 20% of
      controls which was elevated to 60% of women with an ovarian tumor and correlating
      strongly to FSH in the tumor group (P = 0.0002). Steroid hormone levels were
      comparable in the two groups. In women with ovarian tumors the survival time for
      the i.r. inhibin-producing women was found to be 4.6 years compared with 0.9
      year, or 5.1 times longer than in the non-producing women (P = 0.002). The site
      of i.r. inhibin production in these post-menopausal women is unknown, but i.r.
      inhibin production by the developing ovarian tumor or by the post-menopausal
      ovary may be regarded as a defense mechanism against an elevated gonadotrophin
      level (the gonadotrophin theory) which would promote further tumor growth. The
      recent suggestion that the alpha subunit of inhibin is a tumor suppressor gene is
      consistent with these results. The serum i.r. inhibin or alpha subunit
      concentrations might be used as an aid to diagnosis or as a prognostic indicator
      of survival in women with an ovarian carcinoma.

PMID- 8157139
TI  - The post-operative gonadotropin level in post-menopausal women with epithelial
      ovarian cancer.
AB  - Serial estimates of the post-operative hormone levels were made in 15 women
      subjected to oophorectomy because of ovarian carcinoma. All women were post
      menopausal. Pre-operatively, they had significantly lower follicle stimulating
      hormone (FSH) levels compared with an age-matched control group. Blood samples
      were collected after a median time of 8 months (139-378 days). After
      oophorectomy, significantly higher FSH values were found (P = 0.0002), whereas
      the luteinizing hormone (LH) values were not significantly changed. The inhibin,
      estradiol and progesterone values were found to be significantly lowered compared
      with the pre-operative sample. Total and unbound testosterone levels were
      significantly lower while dehydroepiandrosterone sulphate (DHEAS) and
      androstenedione levels were unchanged compared with the original sample and
      compared with controls. Most likely, estradiol and progesterone are produced by
      the epithelial malignant tumors, as the post-operative values are completely
      comparable with the primarily included healthy controls. The FSH is suppressed by
      inhibin and only to a minor degree by the steroid hormones as indicated by the
      correlation coefficients. Of great interest is the question whether inhibin
      production is random, or defensive, lowering the gonadotropin levels or
      influencing tumor growth in some hitherto unknown fashion.

PMID- 8157140
TI  - A 2-year study on the beneficial effects of 17 beta-oestradiol-dydrogesterone
      therapy on serum lipoproteins and Lp(a) in postmenopausal women: no additional
      unfavourable effects of dydrogesterone.
AB  - INTRODUCTION: Postmenopausal hormone replacement therapy (HRT) has been described
      to reduce the risk of developing cardiovascular disease (CVD), which can be
      attributed at least in part to beneficial effects of oestrogens on serum
      lipoproteins. Little is known about a possible counteracting effect by the
      progestogen integrated in modern HRT regimens. OBJECTIVE: To study the possible
      changes in serum lipids, lipoproteins and apolipoproteins during HRT with special
      emphasis on the possible progestational effect. STUDY DESIGN: In an open-label
      longitudinal non-comparative study 23 healthy non-hysterectomized postmenopausal
      women were treated with continuous micronized 17 beta-oestradiol, 2 mg daily, in
      combination with cyclic dydrogesterone, 10 mg daily, the first 14 days of each 28
      day treatment cycle. The women were followed for up to 2 years. RESULTS: After 2
      years serum total cholesterol and low-density lipoprotein cholesterol had
      decreased by 9.0% and 18%, respectively (P < 0.01), while high-density
      lipoprotein cholesterol had increased by 13% (P < 0.01). The latter change was
      accompanied with similar increases in apolipoprotein A-I (+16%; P < 0.01) and A
      II (+13%; P < 0.01), while apolipoprotein B remained unchanged. Serum very low
      density lipoprotein (VLDL) cholesterol and VLDL-triglycerides increased by 28%
      and 21%, respectively, the latter reflecting the slight increase in serum
      triglycerides by 21%. These values, however, remained within the normal range.
      Serum lipoprotein(a) decreased by 16% (P < 0.01). All calculated atherogenic
      indices decreased (P < 0.01) during the study period. Serum lipids and
      (apo)lipoproteins did not change after withdrawal of dydrogesterone for 14 days
      during the combination therapy in the last cycle studied. Serum fibrinogen
      decreased by 8.4% (P < 0.01) in the first 12 cycles, after which it increased to
      13% above baseline value (P < 0.01 vs. baseline). Antithrombin III did not change
      and serum glucose decreased by 5.7%. CONCLUSIONS: This HRT regimen induces (and
      also when given for a longer period) beneficial changes in the lipid profile,
      without affecting important indicators of thrombosis. Also, the glucose
      metabolism does not seem to be interfered with. Cyclic administration of
      dydrogesterone does not unfavourably affect serum lipids and (apo)lipoproteins
      when combined with 17 beta-oestradiol supplementation. Therefore, this
      combination hormone regimen can be recommended for use in HRT.

PMID- 8157141
TI  - Comments by the 'Information by Phone' Department of the Sex Medical Institute on
      the telephone calls related to sexuality and contraception.
AB  - The present study which was carried out by the Sex Medical Institute has been
      based on 5252 telephone calls related to sexual or contraception matters, which
      were received in the period February 1989 to July 1991. Of the calls, 58.8% came
      from men and 41.2% from women. The main topics of the questions concerned
      masturbation (frequency, guilts), anatomy of the genital system (anxiety and
      concern on the length of the penis, virility, femininity), the first sexual
      experience (fear, anxiety of failure).

PMID- 8157142
TI  - Endometrial amoebiasis.
AB  - A case of endometrial infection by Entamoeba histolytica is described in an
      elderly lady who presented with profuse vaginal discharge and was clinically
      misdiagnosed as endometrial carcinoma.

PMID- 8157143
TI  - Cytomegalovirus infection in the pregnant women.
AB  - Cytomegaloviruses (CMV) commonly infect man but overt disease only occurs in few
      patients; in the vast majority the infection is subclinical. We report on a HIV
      negative pregnant woman. She suffered from a life-threatening ulcerating colitis
      due to CMV infection for which laparotomy was indicated. The case history is
      presented and suggestions are given for the surgical treatment of
      gastrointestinal complications such as haemorrhage, toxic colitis and
      perforation. Although CMV disease usually occurs in immunocompromised patients
      such as AIDS patients and transplant recipients, one should always keep the
      possibility of CMV infection in mind. The gastrointestinal tract is one of the
      sites of infection where the colon and terminal ileum are most frequently
      involved in complications such as bleeding and perforation. Gastrointestinal
      complications of CMV infection, although rare, can be life threatening and often
      require extensive surgery.

PMID- 8157145
TI  - Breast cancer: effect of tamoxifen on the mineral density of bone.

PMID- 8157144
TI  - Successful pregnancy after combined pancreas-kidney transplantation.
AB  - In this paper we report a successful pregnancy after combined pancreas-kidney
      transplantation. During pregnancy the patient was treated with prednisone and
      cyclosporin. Pancreatic and renal function remained normal during pregnancy, but
      moderate hypertension was detected in the 28th week. A healthy baby of 1900 g
      (below the tenth percentile) was born at 36 weeks. In this case, urine pregnancy
      tests were negative throughout the pregnancy, probably due to the exocrine
      secretion of the pancreas, which had been diverted to the urinary bladder. This
      possibility has not been previously reported.

PMID- 8157146
TI  - Transcutaneous PCO2 during labor--a comparison with fetal blood gas analysis and
      transcutaneous PO2.
AB  - Reduction of lethal and compromised fetal outcome is a benefit of rising socio
      economic standards and better health care, including technologies such as
      cardiotocography and fetal blood analysis. The pursuit of higher standards in
      obstetrics leads to new and improved techniques. The transcutaneously measured
      carbon dioxide tension (tc PCO2) was proposed as a continuous and non-invasive
      method revealing the acid-base status of the fetus. Nonetheless, intrapartum
      surveillance by measuring tc PCO2 is rarely used in clinical practice. To assess
      the value of fetal monitoring by tc PCO2 during parturition, tc PCO2 measurements
      were compared with the fetal acid-base status. Tc PCO2 was measured by a recently
      developed electrode during 21 deliveries. The tc PCO2 electrode was disinfected,
      calibrated and applied to the presenting part of the fetus after rupture of
      membranes. The acid-base status of the fetus was determined with a commercial
      blood gas analyser in capillary blood (n = 33) and umbilical artery samples (n =
      15). Tc PCO2 was correlated with the PCO2 of the capillary blood (r = 0.56; n =
      33; P < 0.001) as well as with the PCO2 in the umbilical artery (r = 0.75; n =
      15; P < 0.01). The pH value of capillary blood was related to tc PCO2 (r = -0.56;
      n = 33; P < 0.001). However, tc PCO2 did not show a significant relation with the
      pH value in the umbilical artery (r = -0.34; n = 15). Variations in skin blood
      flow are known to decrease the transcutaneously measured oxygen tension (tc PO2)
      below the PO2 in the capillary and umbilical blood.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8157147
TI  - The introduction of external cephalic version at term into routine clinical
      practice.
AB  - External cephalic version (ECV) at > or = 37 weeks' gestation in suitable women
      with breech presentation was introduced in 1991 as a new management option at a
      University Teaching Hospital. After 16 months, the policy was audited by
      analysing a prospectively collected database of women offered ECV at term and by
      a retrospective review of all breech deliveries during the same period. A total
      of 52 women had ECV attempted with an immediate success rate of 46%. Four other
      cases had undergone spontaneous version by the time they attended for ECV. Of the
      remaining 72 breech deliveries, 49 were known to be breech and were not offered
      ECV; 39 of these had no contraindication (28% failure to offer ECV). Of the
      breech presentations, 22 remained undiagnosed until labour (18% of total study
      group). These results suggest that ECV at term can be introduced safely and
      without difficulty, with a strict protocol. Whilst the overall impact of ECV at
      term in clinical practice may be limited, if some vaginal breech deliveries and
      caesarean sections can be avoided it is a useful addition to the antenatal
      management of individual women with breech presentation.

PMID- 8157148
TI  - Complications of diagnostic ultrasound-guided percutaneous umbilical blood
      sampling: analysis of a series of 341 cases and review of the literature.
AB  - OBJECTIVE: To study the complications of percutaneous umbilical blood sampling
      (PUBS) conducted for purely diagnostic purposes, in a retrospective study of 341
      personal cases and an analysis of 4922 cases from literature. SUBJECT: Analysis
      of the sampling procedure and complications seen in 341 punctures, including 12
      failures. INTERVENTIONS: Freehand echo-guided percutaneous umbilical blood
      sampling. PARAMETERS STUDIED: Conditions in which the blood samples were taken
      (gestational age, indications, placental location, technique--including number of
      punctures, duration); total number of fetal deaths and number of fetal deaths
      related to the procedure; other complications (bradycardia, hematoma of the
      umbilical cord, hemorrhage, premature births). RESULTS: 20 fetal deaths (FDs)
      were recorded in 341 cases (5.87%) (figures for the literature: 189/4922 =
      3.84%); 3 FDs appeared to be directly related to the procedure (0.88) (figures
      for the literature: 48/4922 = 0.98%). There were 32 cases of bradycardia (9.38%);
      this complication was seen more frequently after repeated and prolonged
      punctures. Hematomas of the cord (1.47%) were seen when punctures were attempted
      in a free loop of the cord. There was a marked increase in the number of
      complications (8.96% FDs and 20.73% of bradycardias) when the procedure lasted
      more than 10 min and/or when more than 3 punctures were attempted (33.33% FDs).
      These two occurrences are closely related to the gestational age at which the
      PUBS was conducted, the placental location, the experience of the operators and
      the condition for which the sample was being taken. Pathological pregnancies
      (fetal malformation, disease or hypotrophy of the fetus, diseases of the amniotic
      fluid) had a mortality rate of 11.24% (19/169), whereas fetuses that were
      presumed to be healthy had a lower risk of 0.58% (1/172). CONCLUSIONS: The
      overall mortality (including all fetal and neonatal deaths) appears to be around
      5.0% (between 3.84 and 5.87%), but the mortality rate directly related to the
      procedure seems to be around 1% (between 0.88 and 0.98%). It seems that the fetal
      mortality rate is closely related to: (a) The state of the fetus and thus to the
      indication of the procedure. The higher overall mortality rate observed is
      related to the natural history of the conditions for which the procedure was
      conducted and the time taken to conduct the procedure and the number of
      punctures. This depends on the experience of the teams, on the observation of the
      rule that the attempt should not be prolonged beyond 10 min and no more than 2
      punctures should be attempted in any one session.

PMID- 8157149
TI  - Children in the wider world: compassion and the selfish gene.

PMID- 8157150
TI  - Dyskinetic cerebral palsy and birth asphyxia.
AB  - Of 115 children with dyskinetic cerebral palsy (CP) in the Mersey region, 17 were
      born at term and at an appropriate weight for age, and have preserved cognitive
      abilities. 10 of these are likely to have sustained intrapartum asphyxial brain
      damage as the cause of their CP. In such circumstances, a characteristic pattern
      is usually seen of severe fetal distress occurring late in labour, severe but
      short-lived birth asphyxia and only mild or moderate hypoxic-ischaemic
      encephalopathy. This clinical picture should be distinguished from the pattern of
      birth asphyxia which precedes the development of spastic quadriplegic CP.

PMID- 8157151
TI  - Assessment of spasticity in hemiplegic cerebral palsy. II: Distal lower-limb
      reflex excitability and function.
AB  - A clinical method for measuring the stretch reflex threshold and gain of muscles
      acting across the ankle joint in children with congenital hemiplegia is
      described. The stretch reflexes of all limbs were velocity-dependent. Hemiparetic
      limbs were not necessarily spastic compared with non-paretic limbs, suggesting
      that the term 'spastic hemiplegia' should be used more selectively and emphasis
      be placed on the heterogeneity of the hemisyndromes of childhood. Abnormal motor
      control, planning and dexterity, the hemipostures and plastic (non-electrical)
      muscle changes may be more important measures of impairment than reflex
      excitability. A general scheme for assessing reflex excitability and available
      treatments applicable to all types of cerebral palsy is proposed.

PMID- 8157152
TI  - Sleep abnormalities in patients with severe cerebral palsy.
AB  - The all-night polysomnographic findings of nine patients with spastic
      quadriparesis (mean age 36.7 months) were analysed retrospectively and compared
      with those of nine age-matched controls (mean age 37.4 months). The cerebral
      palsy group had significantly more respiratory disturbances per hour of sleep,
      with five of nine being diagnosed as having obstructive sleep apnea. They also
      had fewer changes in body position during the night. Interictal epileptiform
      discharges averaged 23.3 per cent of the total arousals in the cerebral palsy
      group. Obstructive apnea, decreased ability to change body position, and
      interictal epileptiform discharges are prevalent in the sleep of patients with
      severe cerebral palsy, and contribute towards its disruption.

PMID- 8157154
TI  - Eye-poking.
AB  - Eye-poking, -rubbing and -pressing are often incorrectly grouped together because
      of the assumption that they represent variations of the same self-stimulating
      behaviour. This prospective study of 21 children shows that eye-poking is a
      distinct, chronic, stereotyped, self-injurious act seen mainly among severely
      mentally disabled individuals, who may or may not be visually impaired. Eye
      poking, which leads to intense, self-induced pain, is a harmful behaviour because
      it can result in permanent visual loss and even in total blindness. The cause is
      unclear, although it is probably multifactorial. The treatment is exceedingly
      difficult. Further studies are needed to develop specific management techniques
      to prevent eye-poking, which adds to the physical and emotional burden on the
      caregivers.

PMID- 8157153
TI  - Effects of prenatal exposure to PCBs on the neurological function of children: a
      neuropsychological and neurophysiological study.
AB  - To determine the long-term neurotoxicity of prenatal exposure to polychlorinated
      biphenyls (PCBs), 54 children--27 'Yu-Cheng' ('oil disease') children and 27
      controls--were administered a battery of tests, including the WISC-R, auditory
      event-related potentials (P300), pattern visual evoked potentials (P-VEPs) and
      somatosensory evoked potentials (SSEPs). Full-scale IQ scores on the WISC-R were
      lower for the Yu-Cheng group than for the control group. Mean P300 latencies were
      significantly longer, and P300 amplitude significantly more reduced, in the Yu
      Cheng group than in the control group at Cz and Pz. There were no significant
      difference in peak latencies and amplitudes between the two groups for P-VEPs and
      SSEPs. These findings suggest that prenatal exposure to PCBs tends to affect high
      cortical function rather than the sensory pathway in the developing brain.

PMID- 8157155
TI  - Causes of blindness and severe visual impairment in children in Chile.
AB  - Three hundred and eighteen of 421 children (76 per cent) registered in Chile's 10
      schools for the blind were examined. 84 per cent of these had severe visual loss
      (severe visual impairment or blindness), which was attributable to hereditary
      factors in 29.6 per cent, intra-uterine factors in 8.2 per cent, perinatal
      factors in 22.5 per cent and childhood factors in 11.2 per cent. The aetiology
      could not be determined in 28.5 per cent. Retinopathy of prematurity (ROP)
      accounted for 17.6 per cent of all children with severe visual loss; analysis of
      data by age-group suggested that ROP is becoming an increasingly important cause
      of blindness. It is estimated that one-half of the children with severe visual
      loss in Chile have avoidable causes of blindness. The findings are discussed in
      the light of possible control strategies.

PMID- 8157156
TI  - Neurobehavioural relationships after the onset of puberty.
AB  - The behavioural and cognitive development were studied of 68 children with and
      259 without minor neurological function (MND) at 14 years, when the majority of
      children showed three or more physical signs of puberty. MND was differentiated
      into fine manipulative disability, co-ordination problems, choreiform dyskinesia
      and hypotonia. The normal group was subdivided into those who had been normal at
      12 years and those who had had MND. All types of MND were related to cognitive
      and behavioural problems. Fine manipulative disability was related to behavioural
      and cognitive difficulties; co-ordination problems to learning difficulties; and
      choreiform dyskinesia and hypotonia were related to attention difficulties and
      school failure, notwithstanding normal IQ. Besides MND, socio-economic class,
      family adversities and female gender contributed to the development of
      behavioural and cognitive problems. The behaviour of children with MND at 12
      years who were normal at 14 years did not differ from that of normal children.

PMID- 8157158
TI  - Unusual magnetic resonance and neuropathological findings in hemimegalencephaly:
      report of a case following hemispherectomy.
AB  - Hemimegalencephaly is a rare disorder manifest by early epilepsy, mental
      retardation and hemiplegia. The neuropathology has been described in only 15
      cases to date. The present case provides a further description of the pathology
      in a hemispherectomy specimen and shows unusual features, including cystic
      breakdown of the white matter possibly related to the long duration of the
      features, including cystic breakdown of the white matter possibly related to the
      long duration of the disease; the subject was 13 years older than previously
      documented cases. MRI findings were also unusual in showing mass effect and
      ventricular compression in the affected hemisphere, features not previously
      described in hemimegalencephaly.

PMID- 8157157
TI  - Autism in thalidomide embryopathy: a population study.
AB  - Of a population of 100 Swedish thalidomide embryopathy cases, at least four met
      full criteria for DSM-III-R autistic disorder and ICD-10 childhood autism.
      Thalidomide embryopathy of the kind encountered in these cases affects fetal
      development early in pregnancy, probably on days 20 to 24 after conception. It is
      argued that the possible association of thalidomide embryopathy with autism may
      shed some light on the issue of which neural circuitries may be involved in
      autism pathogenesis.

PMID- 8157159
TI  - Ophthalmoplegia in childhood.

PMID- 8157160
TI  - Fungal extracts in clinical practice.
AB  - Sensitivity to fungi is a common clinical problem. Although many commercial
      extracts for diagnosis and treatment of fungal sensitivity are available, there
      is a lack of standardized materials. New research into the isolation and
      purification of fungal allergens may improve upon this situation. Controlled
      immunotherapy trials with fungal extracts have identified selected populations
      who may benefit from this type of therapy.

PMID- 8157161
TI  - Issues in allergen extract mixes.

PMID- 8157162
TI  - Evaluation of delayed hypersensitivity: from PPD to poison ivy.
AB  - Intact cell mediated immunity (CMI) requires a complex interaction between
      lymphocytes, macrophages, and cytokines. The presence of functional CMI can be
      easily tested in vivo by delayed hypersensitivity (DTH) skin testing. Delayed
      hypersensitivity skin testing has been commonly used in three ways; anergy
      screening, testing for infection with intracellular pathogens, and testing for
      sensitivity to contact allergens. Accurate anergy screening requires intradermal
      testing with four or more common recall antigens such as Candida albicans,
      tetanus toxoid, mumps, and purified protein derivative. Problems of antigen
      potency and availability can be overcome by using a multiple time test-like
      device that contains seven different recall antigens (Multitest CMI). Although
      testing for infection was once common, it is now only recommended for
      tuberculosis screening because most other antigens are either not predictive of
      infection or not commercially available. Accurate testing for contact allergy
      requires careful attention to technique, and limitation of allergens to the 20
      antigens that are approved by the American Academy of Dermatology.

PMID- 8157163
TI  - Physiologic pulmonary diagnosis: the spectrum of impairments.

PMID- 8157164
TI  - New approaches in the therapy of immunodeficiency.

PMID- 8157165
TI  - What physicians should know about the antitrust laws.

PMID- 8157166
TI  - Discovery and rediscovery.

PMID- 8157167
TI  - Immunologists honored by commemorative and special issues of postage stamps.

PMID- 8157168
TI  - The genetic basis of response in mouse lines divergently selected for body weight
      or fat content. I. The relative contributions of autosomal and sex-linked genes.
AB  - Lines of mice have been divergently selected for over forty generations on either
      body weight or fat content. Reciprocal crosses were made between the divergent
      lines and the offspring backcrossed to the parental lines. The resulting data
      allowed us to investigate the genetic basis of response, including two features
      of particular interest: (i) the relative contribution of autosomal and sex-linked
      genes and whether any significant Y chromosome or cytoplasmic effects were
      present (ii) the mechanism of gene action, whether predominantly additive or
      whether significant dominance effects were present. A large additive sex-linked
      effect was observed in lines selected on body weight which accounted for
      approximately 25% of the divergence. The remaining 75% of the divergence appeared
      to be autosomal. There was no apparent sex-linked effect in lines selected on fat
      content and the response appeared to be entirely autosomal and additive.

PMID- 8157169
TI  - The genetic basis of response in mouse lines divergently selected for body weight
      or fat content. II. The contribution of genes with a large effect.
AB  - Gene action underlying selection responses has been studied using crossbreeding.
      Maximum likelihood based segregation analysis has been presented for analysing
      backcross data for the presence of genes with a large effect. Two sets of
      divergently selected lines (P-lines for body weight and F-lines for fat content)
      were reciprocally crossed and the F1s were crossed to the high and low lines to
      produce all possible backcrosses. Earlier analysis had shown that the difference
      in body weight at 10 weeks (n = 595) between the high and low P-lines was largely
      (75-80%) explained by autosomal, additive genes with the remainder explained by
      additive genes on the X chromosome. Maximum likelihood segregation analysis
      suggested the presence of a major effect on the X chromosome, but as there was
      only one round of recombination between the X chromosomes in the forming of the
      backcrosses, linked genes on the X chromosome could have acted together to give
      the appearance of a single major gene. The difference in fat content between the
      F-lines (n = 578) could be explained by autosomal genes of largely additive
      effect. Segregation analysis suggested the presence of a major gene with complete
      dominance, but this was attributed to a relationship between the mean and the
      variance: transformation of the data resulted in only polygenic additive genes
      being of importance. This study concluded that maximum likelihood based analysis
      and crosses between selected lines provide a powerful means for studying the gene
      action underlying responses to selection.

PMID- 8157170
TI  - Inheritance of a meiotic abnormality that causes the ovulation of primary oocytes
      and the production of digynic triploid mice.
AB  - Previous studies have demonstrated that the LT/SvKau strain of mice ovulates a
      high proportion of oocytes as diploid primary oocytes rather than secondary
      oocytes. These ovulated primary oocytes are arrested at meiotic metaphase I but
      may be fertilized to produce digynic triploid embryos. In the present study,
      40.4% of eggs analysed from LT/SvKau females were ovulated as primary oocytes,
      compared to 1.2% from control C57BL/Ws strain mothers. These two inbred strains
      were intercrossed to produce eight sets of F1, F2 and backcross females and the
      frequency of triploidy was investigated. The results are compatible with
      segregation of a co-dominant, autosomal gene that has a major influence on the
      incidence of triploidy. We suggest that the provisional gene symbol Poo (primary
      oocyte ovulation) be assigned to this gene, with alleles Poo(l) (the 'mutant'
      allele present in the LT/SvKau strain) and Poo(b) (the normal allele present in
      C57BL/Ws mice). Poo is incompletely penetrant and has variable expressivity
      because the proportion of oocytes ovulated as primary oocytes by LT/SvKau mice
      was variable and, in some cases, nil. In putative Poo(l)/Poo(b) heterozygotes the
      frequency of ovulated primary oocytes was increased only marginally (from 1.2% to
      6.6%) by the presence of one copy of the Poo(l) allele, but this increase was
      found consistently (in two reciprocal F1 crosses) and was statistically
      significant. No evidence was found for tight genetic linkage between Poo and two
      Mendelian loci (brown on chromosome 4 and glucose phosphate isomerase on
      chromosome 7), that were segregating in the crosses. The Poo(l) mutant in the
      LT/SvKau strain of mice provides a valuable resource to study the cell and
      molecular biology of mammalian oocyte maturation and the control of meiosis.

PMID- 8157171
TI  - Detection of quantitative trait loci from frequency changes of marker alleles
      under selection.
AB  - A method was developed to estimate effects of quantitative trait loci (QTL) by
      maximum likelihood using information from changes of gene frequency at marker
      loci under selection, assuming an additive model of complete linkage between
      markers and QTL. The method was applied to data from 16 molecular and coat colour
      marker loci in mouse lines derived from the F2 of two inbred strains which were
      divergently selected on 6-week weight for 21 generations. In 4 regions of the
      genome, marker allele frequencies were more extreme than could be explained by
      sampling, implying selection at nearby QTL. An effect of about 0.5 standard
      deviations was located on chromosome 11, and accounted for nearly 10% of the
      genetic variance in the base population. QTL with effects as small as 0.2
      phenotypic standard deviations could be detected. For typing of a given number of
      individuals, the power of detection of QTL is very high compared to, for example,
      analysis of an F2 population. The joint effects of linkage and selection were
      investigated by Monte Carlo simulation. Marker gene frequencies change little as
      a consequence of selection at a QTL unless the marker and QTL are less than about
      20 cM apart.

PMID- 8157172
TI  - Constitutive magnification by the Ybb- chromosome of Drosophila melanogaster.
AB  - Ybb- is an rDNA-deficient chromosome of Drosophila that has often been used in
      magnification experiments to induce high-frequency reversion of bobbed (bb)
      chromosomes. We observed previously that Ybb- causes ring chromosome loss even
      when the rings are bb+, suggesting that Ybb- induces magnifying sister chromatid
      exchanges in bb+ rings. Here we show that the Ybb- chromosome causes low levels
      of bb magnification in bb+ flies. We refer to the ability of Ybb- to bypass the
      rDNA deficiency requirement for magnification as 'constitutive' magnification. We
      have magnified the ribosomal genes on the Ybb- chromosome and analysed the
      revertant chromosomes using genetic and molecular methods. We find that magnified
      Ybb- chromosomes also exhibit constitutive magnifier activity. Molecular analysis
      shows that both type 1 and type 2 intron+ ribosomal gene repeats are associated
      with magnified Ybb- chromosomes. Type 2 introns have been described previously in
      the rDNA of both X and Y chromosomes. However, type 1 intervening sequences are
      thought to be present only in X, but not Y, ribosomal genes. Some of the Ybb-
      type 1 insertions differ from those present in the rDNA of X chromosomes in that
      they contain an EcoRI site, and some may be present in tandem arrays. The
      constitutive magnifier activity of Ybb- may reside either in the structurally
      unusual ribosomal gene intervening sequences associated with the chromosome, or
      in the locus on YL that is required for magnification to occur.

PMID- 8157173
TI  - Interleukin 4, IgG and oligoclonal IgG in aqueous humor of cataract patients.
AB  - We measured interleukin 4, total IgG, IgG-albumin relative concentration ratio,
      and oligoclonal IgG in aqueous humors of patients with uncomplicated senile
      cataracts and cataracts complicated by previous uveitis of unknown etiology. The
      values of all mentioned parameters are significantly elevated in aqueous humors
      of patients with complicated cataracts. The possible implications of our findings
      are briefly discussed.

PMID- 8157174
TI  - Demonstration of nerve fibers in human accessory lacrimal glands.
AB  - To provide morphologic evidence for the innervation of accessory lacrimal glands,
      glands were biopsied and examined using standard transmission electron
      microscopic techniques. Non-myelinated nerve fibers were found in the connective
      tissue between the glandular epithelia where they made contact with glandular
      epithelial cells, myoepithelial cells, vascular endothelial cells, plasma cells
      and fibroblasts. The distances measured between axons and target cells ranged
      from 30 to 130 nm. Where nerve fibers approached cells sustaining a basement
      membrane, their basement membranes fused to form a discrete unit resembling so
      called 'synapses a distance'. Cells with no basement membrane were situated in
      direct contact with the basement membrane of a nerve fiber. Single axons were
      identified between glandular epithelial cells and cells of intralobular ducts.
      Most of these axons contained many small clear vesicles and a few large, dense
      core vesicles, a finding considered typical of cholinergic parasympathetic nerve
      fibers. In addition, one of the axons identified contained small dense core
      vesicles typical of sympathetic nerve fibers. Human accessory lacrimal glands are
      therefore definitely innervated, with parasympathetic structures morphologically
      prevailing over sympathetic structures.

PMID- 8157175
TI  - Influence of suction cup oculopression on corneal astigmatism.
AB  - In 11 (right) eyes of 11 ocularly healthy subjects an artificial stepwise
      intraocular pressure (IOP) elevation was applied by suction cup oculopression.
      The initial negative pressure in the suction cup was 80 mmHg; it was raised in
      steps of 40 mmHg. The median of the corneal astigmatism, measured with a Zeiss
      ophthalmometer, was 0.50 D before oculopression (the values of the 10th and 90th
      percentiles were 0.30 and 1.10 D, respectively). Corneal astigmatism increased to
      2.00 (0.00-5.10) D, 2.25 (1.00-5.55) D, 2.63 (0.63-7.00) D, 3.38 (1.88-6.88) D,
      3.38 (2.83-7.25) D, and 4.38 (2.85-5.63) D with 80, 120, 160, 200, 240, and 280
      mmHg oculopression, respectively. The astigmatism dropped to 0.75 (0.00-2.30) D
      immediately after removal of the suction cup. Thus, suction cup oculopression not
      only influenced IOP but also ocular refraction. This is of particular importance
      since visual evoked potential (VEP) amplitude is to a high degree dependent on
      refractive changes. This fact has to be considered if changes in VEP amplitude
      during suction cup oculopression are used as a tolerance test in glaucoma
      diagnosis.

PMID- 8157176
TI  - Murine experimental autoimmune uveoretinitis induced by interphotoreceptor
      retinoid-binding protein and Klebsiella pneumoniae 03 lipopolysaccharide (K03
      LPS): a relation between H-2 haplotype and EAU induction.
AB  - The pathogenicity of interphotoreceptor retinoid-binding protein (IRBP) in the
      mouse and H-2 restriction of IRBP-induced experimental autoimmune uveoretinitis
      (EAU) was tested by repeated immunization using Klebsiella pneumoniae 03
      lipopolysaccharide (K03-LPS) as an adjuvant. It was shown that IRBP had a greater
      capacity to induce EAU than S-antigen. Based on the incidence of EAU induction
      using B10 congenic mice and other strains, the susceptibility to EAU was, at
      least in part, controlled by the I-Ak haplotype of the H-2 subregion. The results
      also indicated that non-major histocompatibility complex (MHC) genes play some
      role in disease susceptibility.

PMID- 8157177
TI  - The age of onset of posterior vitreous detachment.
AB  - The age of onset of posterior vitreous detachment (PVD) was studied in 930 eyes
      with a clearly defined onset time and no vitreoretinal diseases except refractive
      error or equatorial degeneration. We found a positive correlation between onset
      age of PVD and refractive error, with the regression line y = 0.91 x + 60.93 (y
      onset age, x diopter of refractive error). The higher the degree of myopia, the
      younger the onset age of PVD. Comparing onset ages for 240 eyes from males and
      690 eyes from females, there was a possible tendency toward a lower PVD onset age
      for females. There was no significant difference in onset age between 112 eyes
      with and 818 eyes without equatorial degeneration of the retina.

PMID- 8157178
TI  - Glucose concentration in the vitreous of nondiabetic and diabetic human eyes.
AB  - Glycation (nonenzymatic glucosylation) of collagen may play a role in the primary
      pathology of the vitreous in diabetes. The extent of glycation is determined by
      the glucose concentration in the tissue. In this study glucose concentration was
      assayed in blood and vitreous samples obtained from three patient groups
      undergoing vitrectomy: nondiabetic patients (ND), diabetic patients with insulin
      dependent diabetes mellitus (IDDM) and diabetic patients with non-insulin
      dependent diabetes mellitus (NIDDM). In the ND group the glucose concentration in
      the vitreous (3.5 +/- 1.8 mM/l) was always lower than in the blood (9.1 +/- 3.5
      mM/l). In the diabetic groups the vitreous glucose concentration was, with a few
      exceptions, generally lower than the blood glucose concentration. The vitreous
      glucose concentration in these groups was generally higher (IDDM 9.4 +/- 3.3
      mM/l, NIDDM 7.2 +/- 3.9 mM/l) than in the ND group, and in 15 specimens exceeded
      11 mM/l, a level increasing the probability of collagen glycation in the vitreous
      of diabetic patients.

PMID- 8157179
TI  - Prognostic value of initial electroretinogram in central retinal vein
      obstruction.
AB  - We retrospectively studied the correlation between the initial electroretinogram
      (ERG) recordings and the final visual acuities (VA) of 47 patients with central
      retinal vein obstruction (CRVO) after follow-up of more than 1 year. The a- and b
      wave amplitudes and the b/a ratio with white flash were significantly larger in
      patients with good vision (VA > 20/200) than in those with poor vision (VA < or =
      20/200). The b/a ratio and b-wave amplitude with white flash showed sensitivity
      and specificity of more than 78% for visual prognosis. The latest VA was < or =
      20/200 in all 20 patients with a subnormal b-wave amplitude and in all 15 with
      b/a ratio < 1.05. These results suggest that the ERG recorded soon after (CRVO)
      onset correlates strongly with visual prognosis.

PMID- 8157180
TI  - Circulating cornea-specific antibodies in corneal disease and cornea
      transplantation.
AB  - In order to establish the significance of circulating cornea-specific antibodies,
      we determined the presence of anti-corneal antibodies in the serum of 100
      patients with corneal disease and in 50 healthy controls, and subsequently
      followed the pattern of antibody reactivity in 46 patients who underwent corneal
      transplantation. An indirect immunofluorescence test on cryostat sections of
      rabbit corneas was used for screening. The reactivity against two known bovine
      corneal epithelial proteins was also tested: a 54-kD protein (BCP 54) and an 11
      kD protein (BCP 11/24). No significant difference in the presence and specificity
      of anti-corneal antibodies was observed between the group of patients with
      corneal disease, taken as a whole, and the healthy controls. Patients with
      keratoconus or non-immunological graft failure, however, were significantly more
      often positive for anti-corneal antibodies. Neither the presence of antibodies
      prior to corneal transplantation nor their appearance post-transplantation had a
      predictive value for corneal graft survival.

PMID- 8157182
TI  - The British Society of Gastroenterology Spring Meeting. March 23-25, 1994.
      Abstracts.

PMID- 8157181
TI  - Changes in the retinal pigment epithelium close to retinal vessels in familial
      adenomatous polyposis.
AB  - Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is known to
      occur in patients with familial adenomatous polyposis. Its relation to the course
      of the retinal blood vessels is emphasized in this publication. A 15-year-old
      girl with familial polyposis coli showed a longitudinal strip of whitish change
      following the course of a superior nasal artery of the left eye, falsely
      appearing to enclose the blood vessel like a sheath. A 34-year-old woman from
      another family with polyposis coli also showed a longitudinally orientated area
      of hypo- and hyperpigmentation close to temporal retinal veins. Two further
      patients revealed hyperpigmentation of the RPE under retinal vessels. It is
      hypothesized that these changes indicate an effect of the hypo- and
      hyperpigmentations of the RPE on the development of retinal vessels. In four
      patients, multiple dotlike hyperpigmentations were found in the extreme periphery
      of the retina; however, the bigger patchy hyperpigmentations were predominantly
      located in the midperiphery of the retina.

PMID- 8157183
TI  - The obsolescence of second-look laparotomy in the management of malignant ovarian
      germ cell tumors.

PMID- 8157184
TI  - Second-look laparotomy in ovarian germ cell tumors: the gynecologic oncology
      group experience.
AB  - The Gynecologic Oncology Group (GOG) experience with second-look laparotomy in
      malignant ovarian germ cell tumors is reviewed. All patients in this study were
      enrolled prospectively on one of three protocols that employed relatively brief
      cisplatin-based chemotherapy after initial surgical staging and cyto-reduction.
      Forty-five surgical procedures were done in patients who received three courses
      of cisplatin-based adjuvant therapy after complete tumor resection. Findings were
      no tumor or mature teratoma in 43; 2 patients had immature teratomas. One of the
      latter patients received further chemotherapy and one did not. Both of these
      patients and 44 of the total are disease free. Seventy-two patients were treated
      with similar chemotherapy for advanced incompletely resected tumor. Forty-eight
      of these patients did not have teratoma elements in their primary tumor. At
      surgery, 45 patients had no tumor and 3 had persistent endodermal sinus tumor or
      embryonal carcinoma. All three of the latter patients are dead despite further
      treatment. Twenty-four patients had teratoma elements in their primary tumor. Of
      these patients, 16 had mature teratoma at second-look, which in 7 was bulky or
      progressive. Fourteen of the total 16 and 6 of the 7 with bulky residual tumor
      remain disease free after surgical resection. Second-look laparotomy is not
      necessary in patients completely resected initially or in those patients with
      advanced tumor that does not contain teratoma. However, enough patients with
      incompletely resected tumor which initially contains elements of teratoma benefit
      from the procedure to warrant its general use.

PMID- 8157185
TI  - Ovarian stimulation and breast cancer: is there a link?
AB  - The results of both epidemiologic and experimental studies suggest that
      endogenous (and apparently exogenous) sex hormones and other reproductive
      variables have an important role in the development of human breast neoplasia.
      Nevertheless, no controlled study has ever addressed the possible effects of
      ovarian stimulation on the incidence and course of human breast cancer. Over the
      past decade the number of women undergoing follicular stimulation, especially
      during assisted reproductive technology procedures, has grown rapidly. Here we
      present 16 cases of young women who were treated by induction of ovulation, and
      subsequently were diagnosed with breast cancer. These women were drawn out of 950
      cases of infertile women who underwent induction of ovulation at our fertility
      clinic over a 10-year period. The possible association between ovarian
      stimulation and promotion of breast cancer is discussed and the need for a
      controlled study is emphasized.

PMID- 8157186
TI  - Enterovesical fistula following radiotherapy for gynecologic cancer.
AB  - Enterovesical fistula is a rare complication of pelvic radiotherapy. Recurrent
      disease is the cause of fistulization in most patients. We identified 14 patients
      who developed enterovesical fistula in the absence of tumor recurrence. These
      women were at high risk for radiation morbidity due to prior surgery, pelvic
      inflammatory disease, adjuvant hyperbaric oxygen, or locally high doses of
      radiotherapy caused by suboptimal geometry and technique. All patients underwent
      radiographic imaging including barium enema, intravenous pyelogram, and upper
      gastrointestinal study with small bowel follow-through. The range of radiation
      morbidity was great: some patients had small fistulae, others had extensive
      fistulization and radionecrosis. Six patients had colovesical fistulae, five had
      enterovesical fistulae, and three had fistulae involving both the small and large
      bowel. Twelve patients underwent 13 surgical procedures. Healing or successful
      repair of the fistula was achieved in 1 of 3 patients treated with diversion
      (loop colostomy), 2 of 4 patients treated with isolation of the fistulized bowel
      loop and urinary conduit, and 5 or 6 treated with bowel resection with or without
      urinary conduit. Two of three perioperative deaths occurred in the isolation
      group managed without urinary conduit and were related to ongoing sepsis.
      Surgical procedures which resect necrotic fistulized bowel and result in complete
      separation of the gastrointestinal and genitourinary tracts provided the best
      results in patients with radiation-induced enterovesical fistulae. CT scan of the
      abdomen and pelvis is recommended in the evaluation of the majority of patients
      with suspected enterovesical fistula.

PMID- 8157187
TI  - Experience with the management of ovarian germ cell tumors in Chinese patients.
AB  - Treatment results of 37 consecutive patients with primary ovarian germ cell
      tumors (OGCTs) were analyzed. Thirty-three were referred after initial laparotomy
      and four were first seen at relapse. Four patients with stage I dysgerminoma and
      grade 1 immature teratoma were observed after operation without recurrence. There
      was also no relapse in eight patients with dysgerminoma given postoperative
      irradiation (whole abdomen, median 30 Gy). Twenty-five patients (3 dysgerminomas,
      11 immature teratomas, 9 endodermal sinus tumors, and 2 mixed germ cell tumors)
      received short-term cis-platinum-based chemotherapy. Six out of eight measurable
      tumors treated by chemotherapy had complete remission. Complete follow-up
      information was obtained in 35 out of 37 patients. The 4-year actuarial survival
      rates of the whole group and those referred immediately after initial surgery
      were 94.1 and 100%, respectively. cis-Platinum was substituted by carboplatin in
      eight cases but this did not affect treatment result. Nonetheless, deaths
      occurred in two of four patients referred at relapse with extensive disease and
      initially treated with suboptimal regimens. Chemotherapy-induced side effects
      were common but mostly tolerable and were related to cis-platinum and bleomycin.
      The results of this series show that cis-platinum-based chemotherapy is so
      effective that nearly 100% cure can be achieved in OGCTs and suggest that it is
      important to institute optimal chemotherapy from the start. On the other hand,
      common side effects of treatment and possible late toxicities make it desirable
      for future studies to see whether chemotherapy intensity could be reduced in
      patients with good prognosis.

PMID- 8157188
TI  - Expression of glutathione S-transferase-pi in human ovarian cancer as an
      indicator of resistance to chemotherapy.
AB  - Expression of glutathione S-transferase-pi (GST-pi) was examined
      immunohistochemically in relation to the response to chemotherapy with cisplatin
      in 61 patients with primary ovarian cancer who had not received any chemotherapy
      before surgery. GST-pi were detected in the cancer tissues of 33 patients
      (54.1%). Of 28 clinically measurable lesions after surgery, 10 of the 11 tumors
      (90.9%) showing positive GST-pi staining were drug resistant (no change or
      progressive disease), whereas 6 of the 17 tumors (35.3%) showing negative
      staining were drug resistant. This difference in the response rates of the two
      groups was significant (P < 0.005). The survival period of patients with GST-pi
      positive tumors was also significantly shorter than that of those with GST-pi
      negative tumors (P < 0.005). These data strongly suggest that GST-pi expression
      in tumor cells is related to drug resistance of patients with epithelial ovarian
      cancer and is a useful marker of a poor prognosis.

PMID- 8157189
TI  - Cell density dependence of cAMP and cGMP levels in four human cell lines derived
      from carcinomas of the uterine cervix.
AB  - Several studies have shown altered biokinetics of cyclic nucleotides in human
      cancer. In order to mimic the growing tumor bulk in carcinomas of the uterine
      cervix, four human cell lines (C4-I, C33A, ME-180, and SiHa) were expanded in
      serum-supplemented cell cultures. The extra- and intracellular levels of cAMP and
      cGMP were determined at increasing cell densities. In all of the cell lines, a
      cell density-dependent increase in the extracellular cGMP/cAMP ratio was
      observed. cAMP was distributed to the extracellular compartment against a
      concentration gradient at low cell densities but was retained in the
      intracellular compartment at high cell densities. In contrast, cGMP was
      distributed to the extracellular compartment against a concentration gradient for
      the whole range of cell densities. This study suggests that the cell density
      dependent increase in the extracellular cGMP/cAMP ratio in cell lines derived
      from carcinomas of the uterine cervix is a result of changes occurring in both
      intracellular levels and cellular excretion of cyclic nucleotides.

PMID- 8157190
TI  - Chemotherapy and extended-field radiation therapy to para-aortic area in patients
      with histologically proven metastatic cervical cancer to para-aortic nodes: a
      phase II pilot study.
AB  - From November 1983 to October 1992, 22 patients with invasive cervical cancer
      stage IB through stage IIIB with metastasis to para-aortic nodes were entered in
      this study. Five patients were excluded. Of 17 remaining evaluable patients, 5
      (29%) were stage IB, 6 (35%) were stage IIB, and 6 (35%) were stage IIIB. Four
      (24%) had grade 1, 5 (29%) had grade 2, and 8 (47%) had grade 3 tumor. Lymph node
      metastases were microscopic in 8 (47%) and macroscopic in 9 (53%) patients. All
      patients received 2 courses of chemotherapy concomitant with radiation as a
      sensitizer. They were randomized to receive either cisplatin (regimen A) or
      combination of cisplatin with 5-FU infusion (regimen B). This was followed by
      maintenance chemotherapy with cisplatin for a maximum of 10 additional courses.
      Of 17 patients, 7 (41%) received 4-6 courses, 4 (24%) received 6-8 courses, and 6
      (35%) received 8-10 courses of maintenance chemotherapy. For extended-field
      radiation, a panhandle technique was used. External radiation therapy was
      delivered via 10 or 18 MeV linear accelerator photons, followed by 1 or 2
      intracavitary cesium applications. Patients were followed up 8-103 months (median
      21 months). Progression-free interval (PFI) for all patients was 5-103 months
      (median 18 months). Patients with microscopic metastasis to para-aortic nodes had
      median PFI of 26.5 months compared to 14 months in those with macroscopic nodal
      metastasis. Seven of 17 patients (41%) are alive from 17 to 103 months with
      median survival of 32 months. Overall survival for the entire group was 8-103
      months (median 21 months). Median survival for patients with microscopic and
      macroscopic nodal metastasis was 30 and 21 months, respectively. Two- and five
      year survival for the entire group was 35 and 12%, respectively. The survival
      with microscopic metastasis to para-aortic nodes was 50 and 12% compared to
      survival of 22% at 2 years and 11% at 5 years respectively in those with
      macroscopic nodal metastasis. There was no significant difference between regimen
      A and B for local disease control. Maintenance chemotherapy with cisplatin did
      not appear to significantly improve the 5-year survival. Distant metastases were
      the predominant sites of failure.

PMID- 8157191
TI  - Human papillomavirus DNA in locally recurrent cervical cancer.
AB  - Ten vaginal and central recurrences of cervical carcinoma were analyzed by
      Southern blot hybridization under nonstringent and stringent conditions for the
      presence of human papillomavirus (HPV) type 11, 16, 18, 31, and 35 DNA. Cases
      judged HPV-negative by this assay were tested with the polymerase chain reaction
      (PCR) for HPV 16 and 18. All 10 recurrences were HPV-positive. Seven tumors
      contained HPV 16, one contained HPV 18, one contained HPV 16 and 18, and one
      contained HPV-related sequences. In three cases, where the corresponding primary
      tumor could be studied, the identical HPV type was contained. The consistent
      presence of HPV DNA in local recurrences of invasive cervical carcinoma argues in
      favor of a role of these viruses also in the maintenance and reappearance of
      malignancy.

PMID- 8157192
TI  - Conservative surgery for recurrent or persistent carcinoma of the cervix
      following irradiation: is exenteration always necessary?
AB  - Between 1960 and 1988, 47 patients had conservative surgery for postradiation
      recurrent or persistent cervical carcinoma. Forty-two patients with nonmetastatic
      disease and available follow-up information were divided into 3 groups based on
      the extent of disease and type of surgical procedure. Group 1 contained 13
      patients with smaller tumors prior to radiation (FIGO Ib and IIa), and recurrent
      or persistent disease confined to the cervix and/or vaginal vault. Group 2
      consisted of 20 patients presenting with more advanced disease than those in
      Group 1, at the time of either radiation or surgery. Surgical resection of
      disease was accomplished in both Groups 1 and 2 by either radical vaginal or
      abdominal hysterectomy. The 8 patients in Group 3 required extended Wertheim
      operations to encompass locally advanced disease involving the bladder base
      and/or parametrium. One patient could not be categorized. The 5-year estimated
      relapse-free survivals for each group were 84, 49, and 25%, respectively. The
      relapse-free survival of Group 1 was significantly better (P = 0.003) than that
      of Group 3. Major complications occurred in 4 patients belonging to Group 1
      (31%), 10 in Group 2 (50%), and 6 (including two treatment-related deaths) in
      Group 3 (75%). The most common complication was fistula formation in 11 patients
      (26%). Radical hysterectomy can be offered as an alternative to exenteration in
      carefully selected patients.

PMID- 8157193
TI  - Complications of the ileocolonic continent urinary reservoir (Miami pouch).
AB  - Urinary diversion via the continent ileocolonic reservoir has been performed at
      our institution since February 1988. During a 4-year period, 39 patients have
      received this procedure as an alternative to other forms of cutaneous urinary
      diversion at the time of exenteration. We analyze our data in terms of early and
      late (beyond 6 weeks) complications resulting directly from the operation or from
      this form of urinary diversion. A total of 18 patients (46%) suffered early
      complications resulting in an operative mortality rate of 7% (3 of 39 patients).
      One or more late complications occurred in six patients (15%). Only one patient
      required reoperation for a postoperative complication. With ongoing experience,
      problem areas have been identified that have led us to make modifications in
      technique. We review our experience with the incidence of early and late
      complications in terms of management and ultimate prevention.

PMID- 8157194
TI  - Invasive endometrial cancer in uteri resected for atypical endometrial
      hyperplasia.
AB  - Endometrial hyperplasia (EH) includes a spectrum of lesions with unclear
      malignant potential. To examine the association between the most advanced forms
      of hyperplasia and the occurrence of endometrial cancer, we compared the findings
      of endometrial biopsies or curettings with the subsequent hysterectomy specimens
      in 44 women who underwent hysterectomy for "atypical" EH in the 39-month period
      from January 1, 1989 through April 1, 1992. Endometrial cancer was found in 19
      (43%) of 44 hysterectomy specimens obtained within a mean of 10 weeks of uterine
      sampling. Myometrial invasion was present in 17 (89%) of the 19 specimens with
      cancer, while significant myometrial invasion (FIGO Stage IC or higher) was
      present in 7 (37%), and 4 (21%) were Grade 2 or higher. Preoperative sampling
      method and type of atypical hyperplasia (simple vs complex) were not
      significantly associated with the finding of cancer at hysterectomy. Although
      over one-third of the cancers found were in the less than 50 age group, an age of
      70 or greater was significantly associated with cancer at hysterectomy (P < 0.05,
      Fisher's exact test). In a limited set of hysterectomy specimens for which
      estrogen and progesterone receptor status was assayed (n = 11), there was no
      significant difference between the invasive cancer and EH subsets. Our findings
      suggest that women who are candidates for hysterectomy on the basis of atypical
      EH should be carefully evaluated for the possibility of advanced disease. The
      specimens in these circumstances should be opened upon removal to determine if
      myometrial invasion is present and if further surgical staging is indicated.

PMID- 8157195
TI  - The potential role of serum CA 125 in an ultrasound-based screening program for
      familial ovarian cancer.
AB  - We have assessed the potential role of a test based upon the measurement of serum
      CA 125 in an ultrasound-based screening program for familial ovarian cancer. A
      sample of peripheral blood was taken from 1502 self-referred, asymptomatic women
      whose pedigree showed that at least one close relative had developed the disease.
      All women in the study underwent one screening by transvaginal ultrasonography
      (consisting of one or more scans) to detect any persistent lesion and a change in
      ovarian volume. Women with a positive result were referred for surgery. The
      concentration of serum CA 125 was measured in all samples at the end of the
      study. Seven ovarian cancers (4 invasive and 3 of borderline malignancy; 5 FIGO
      stage Ia, 1 stage IIa, 1 stage III) and 55 benign lesions were detected. We
      calculated the effect that a prescreening test (based on different threshold
      values for serum CA 125) would have had on the number of women entering the
      ultrasound-based screening program, and on the detection rate and false-positive
      rate of the overall procedure. There was a direct relationship between the number
      of women referred for ultrasound screening and the detection rate. The use of a
      threshold value for serum CA 125 > or = 20 U/ml would have meant that 380 women
      (25.3%) were referred for ultrasonography and 5 out of 7 cancers (71%) would have
      been detected with a false-positive rate of 1.1%. The odds of a woman with a
      positive screening result having cancer at surgery would have been about 1:3
      (which would improve to about 1:1 if observational indices of color Doppler
      imaging and a morphological score had been used throughout). We concluded that a
      prescreening immunochemical test based on the measurement of serum CA 125 (with a
      threshold value of > or = 20 U/ml) would increase the prior odds for familial
      ovarian cancer by 2.8, but would lower the overall detection rate by 29% at the
      prevalence screening.

PMID- 8157196
TI  - Elevated serum levels of neopterin and soluble interleukin-2 receptor in patients
      with ovarian cancer.
AB  - Preoperative serum neopterin, soluble interleukin-2 receptor (sIL-2R), and CA125
      levels were assayed in 47 patients with ovarian cancer and 113 patients with
      benign ovarian disease undergoing laparotomy. The cutoff limits of the antigens
      for the preoperative evaluation of ovarian cancer were fixed according to the
      Youden plot, using the patients with benign ovarian disease as controls. These
      limits were 7.9 nmole/liter for neopterin, 71 U/ml for sIL-2R, and 83 U/ml for
      CA125. The preoperative mean values of serum neopterin and sIL-2R were
      significantly higher in patients with ovarian cancer than in those with benign
      ovarian disease. Therefore these tests would seem to be useful in distinguishing
      benign from malignant ovarian masses. Serum levels of neopterin, sIL-2R, and
      CA125 above the cutoff limits were detected in 66.0, 78.7, and 76.6% of patients
      with ovarian cancer. Patients with advanced-stage disease (FIGO > or = III) were
      significantly more likely to have a higher percentage of elevated values of sIL
      2R and CA125, but not neopterin, compared to patients with early-stage disease.
      However, neopterin was the antigen most often raised in early disease. As for
      advanced ovarian cancer, preoperative serum sIL-2R levels were higher in patients
      who developed progressive disease than in those who were progression-free (P =
      0.02) after a median follow-up time of 18 months. Furthermore, a trend to higher
      preoperative serum neopterin values was found in the former patients (P = 0.08).
      Tumor progression occurred in 3 of 8 (37.5%) patients with low serum preoperative
      neopterin (< 7.9 nmole/liter) and in 16 of 19 (84.2%) patients with elevated
      serum neopterin, respectively (P = 0.027). Multivariate analysis on a larger
      number of patients followed for a longer time is warranted to elucidate the
      prognostic relevance of these immunologic markers in ovarian cancer. Changes in
      serum neopterin, sIL-2R, and CA125 levels correlated with the disease course in
      50.0, 54.8, and 92.9% of 42 instances, respectively. Moreover, serum CA125 was
      more sensitive than the other two antigens in the early detection of tumor
      progression. Therefore serial neopterin and sIL-2R measurements seem to be of
      limited value in monitoring the disease course in patients with ovarian cancer.

PMID- 8157197
TI  - Which is more painful? A randomized trial comparing loop with laser excision of
      the cervical transformation zone.
AB  - We compared the pain of excisional cervical surgery by the laser or loop
      diathermy (LLETZ) in a randomised controlled clinical trial. Eighty women with
      CIN III were recruited from a laser colposcopy clinic specifically adapted to run
      randomized trials. They were scheduled for excision of their cervical
      transformation zone and both groups were matched for age, parity, and size of
      lesion. We measured linear analogue pain scores, subjective pain scores, and
      operative time. The laser and loop diathermy inflicts similar discomfort and
      there is no detectable difference between the median pain scores of women in
      either group (P = 0.99). However, in the hands of an experienced surgeon it takes
      4 min extra to excise the cervical transformation zone with a laser compared to
      loop diathermy. The average time from sitting in the chair to the end of the
      procedure was 13.02 min (SD 3.65) for the group allocated diathermy surgery
      compared to 17.30 min (SD 5.33) for a laser excision log transformed t(log
      transformed data) = 3.7 (P < 0.001).

PMID- 8157198
TI  - Uterine papillary serous carcinoma in a 32-year-old with Turner's syndrome.
AB  - The association of Turner's syndrome and endometrial carcinoma has been
      previously established but has never been described in conjunction with a uterine
      papillary serous carcinoma (UPSC). This histological variant is usually found in
      considerably older women and has no clear relationship to the prior use of
      estrogen replacement therapy. Despite presenting with stage IV disease, treated
      by surgery and medroxyprogesterone only, this patient has had an 8-year disease
      free remission, suggesting that radical debulking of an endocrine-responsive
      tumor may be of considerable benefit to some women with this unfavorable
      histological subtype of endometrial carcinoma.

PMID- 8157199
TI  - Primary fallopian tube adenocarcinoma in situ associated with adjuvant tamoxifen
      therapy for breast carcinoma.
AB  - We report the first case of primary fallopian tube adenocarcinoma in situ in a
      patient who had received antiestrogen tamoxifen as adjuvant therapy for breast
      carcinoma. Clinical and in vivo animal model studies, referable to the possible
      estrogen agonist effect of tamoxifen on the female genital tract, are also
      reviewed.

PMID- 8157200
TI  - Lymphatic vaginal fistula after Wertheim-Taussig hysterectomy: a case report.
AB  - Significant vaginal discharge of clear fluid after Wertheim-Taussig hysterectomy
      with bilateral salpingo-oophorectomy is most often due to urinary fistula.
      Rarely, the same symptom may be caused by lymphatic fistula, which has not been
      reported previously. The differentiation between lymph and urine is simple. If
      this rare complication is not suspected, patients may undergo unnecessary
      invasive diagnostic procedures of the urinary tract.

PMID- 8157201
TI  - Wound seeding associated with endometrial cancer.
AB  - We report a patient with well-differentiated adenocarcinoma of the endometrium
      who developed a recurrence in the anterior abdominal wall probably secondary to
      wound seeding at the time of her original surgery. She underwent total abdominal
      hysterectomy, bilateral salpingo-oophorectomy. She then received 15 mCi of 32P
      for positive peritoneal washings. She was free of disease until 2 years later
      when a large lower incision mass developed. She had no evidence for intra
      abdominal disease and a radical resection with a myocutaneous flap was
      undertaken. Radical resection for isolated metastases may be of benefit for
      patients with endometrial cancer. Patients with positive cytology should be
      observed closely for incisional recurrence.

PMID- 8157202
TI  - A case of ovarian cancer with metastasis to the sternum and costae.
AB  - This report describes a case of ovarian cancer with metastases to the sternum and
      costae. Sternal and costal metastases from ovarian cancer are extremely rare. We
      introduce a case of sternal metastasis from ovarian cancer that occurred over 7
      years after initial diagnosis which was successfully treated with local resection
      and systemic chemotherapy. Possible metastatic routes are discussed.

PMID- 8157203
TI  - Ovarian cancer presenting with inguinal metastasis 33 months prior to
      intraabdominal disease.

PMID- 8157204
TI  - Production of a specific monoclonal antibody to terminal deoxynucleotidyl
      transferase (TdT) and the extensive studies of TdT in patients with hematological
      malignancies.
AB  - Terminal deoxynucleotidyl transferase (TdT) was purified from calf thymus and a
      monoclonal antibody-producing clone was produced by the fusion of mouse myeloma
      cells and spleen cells of mice immunized with the purified enzyme. The antigens
      recognized by an immunoadsorbent column revealed TdT, whose molecular weight was
      62 kDa. The extensive study of TdT in 196 patients with hematological disorders
      was done. The results from immunofluorescent analysis corresponded well to the
      results of biochemical assays of this enzyme. This monoclonal antibody will
      provide a useful means for the survey of leukemia and lymphoma patients.

PMID- 8157205
TI  - Expression of human sialophorin (CD43) in a human x mouse somatic cell hybrid.
AB  - We have studied the expression of the human sialophorin (CD43) molecule in a
      human x mouse somatic cell hybrid (H-8). The CD43 molecule was detected on the
      cell surface by immunofluorescence analysis and the hybrid cell possessed human
      chromosome 16 which carries the gene for CD43. Biochemical analysis showed that
      the cell line expressed a low molecular form of CD43, which was due to altered
      glycosylation. The cells reacted with anti-CD43 antibodies but behaved
      differently in response to the antibodies in the aggregation process. This
      indicates the crucial importance of the sugar moieties and epitope position in
      aggregation and subsequent activation mediated by CD43.

PMID- 8157206
TI  - Pyoderma gangrenosum associated with idiopathic myelofibrosis. Case history.
AB  - A case of pyoderma gangrenosum associated with idiopathic myelofibrosis is
      described. It is important to recognise it, since the treatment with
      corticosteroids and sulphonamides is frequently effective.

PMID- 8157207
TI  - Relationship between autoantibody and dermatosis in myelodysplastic syndrome.
AB  - We analyzed the relationship between autoantibody and dermatosis in 22 patients
      with myelodysplastic syndrome (MDS). These MDS patients consisted of five cases
      with refractory anemia (RA), three RA with ringed sideroblasts (RARS), eight RA
      with excess of blasts (RAEB), four RAEB in transformation (RAEB-t), and two
      chronic myelomonocytic leukemia (CMMoL) according to the FAB classification of
      MDS. The autoantibody was detected in seven patients, of whom four had rheumatoid
      factor (RF) and three had antinuclear antibody (ANA). Neither RF-positive nor ANA
      positive MDS patients had other autoantibodies. Dermatosis was observed in nine
      cases of these 22 MDS patients. Five of 7 MDS patients (71%) with autoantibody
      developed dermatosis in their clinical course, as did four of 15 MDS patients
      (27%) without autoantibody. All four MDS patients with RF had dermatosis such as
      anaphylactoid purpura, xerotic dermatitis, thrombophlebitis, ephelides, and
      genital herpes. One of three MDS patients with ANA had pruritus senilis. The four
      MDS patients without autoantibody had dermatosis such as erythema nodosum,
      ichthyosis vulgaris, Sweet syndrome, and thrombophlebitis. Three of four MDS
      patients with RF had normal liver function tests, while three MDS patients with
      ANA showed liver dysfunction. Our studies presented here suggested that the
      dermatosis could develop frequently in MDS patients with autoantibody and that RF
      was closely related to development of dermatosis in MDS patients, although the
      dermatosis is not specially fixed.

PMID- 8157208
TI  - Correlation of in vitro enhancement of erythropoiesis and clinical response to
      steroids in Diamond-Blackfan anaemia.
AB  - To investigate whether the clinical response to steroids in Diamond-Blackfan
      anaemia (DBA) can be predicted in vitro, erythroid cultures from six patients was
      performed. The increment of burst forming unit erythroid (BFU-E) and colony
      forming unit erythroid (CFU-E) derived colonies had been studied with the in
      vitro addition of steroids. Our results showed: 1) a relative insensitivity to
      low and optimum concentration of erythropoietin (Epo) in cultures, and 2) lower
      CFU-E and BFU-E colony formation in all cases studied. (CFU-Es of normal
      controls/10(5) cells; were 85.6, BFU-Es 37.8, while the patients' CFU-E were 18.1
      and BFU-E 7/10(5) cells with two IU of Epo) with poor or no growth in three
      cases, 3) increment up to 60-110% with in vitro addition of steroids in three
      cases, 4) high serum Epo levels in all Diamond-Blackfan anaemia patients, and 5)
      clinical response to steroids in the three patients who responded in vitro.

PMID- 8157209
TI  - The importance of serial immunoglobulin evaluations in HIV-seropositive
      haemophiliacs.
AB  - The aim of our investigation was to evaluate whether the alteration of
      immunoglobulins (Igs) may be a predictive marker of the evolution of HIV
      infection in seropositive haemophiliacs. For this purpose two groups of
      haemophiliac patients (16 seronegative and 21 seropositive) were compared to
      evaluate the variations of the Ig profile over a period of 5 years (1985-1989).
      The two populations were similar for the number of transfusions of blood products
      and for the severity of post-transfusional hepatic disorders. The IgM increase,
      in the first stages of HIV infection, appears to be more discriminant than
      polyclonal elevation of IgG, which is already present in seronegative
      polytransfused haemophiliac patients.

PMID- 8157210
TI  - Evaluation of experimentally induced enzymatic alterations on the erythrocyte
      membrane by use of alcian blue.
AB  - The binding of the polycationic dye alcian blue to erythrocytes is investigated
      at pH 6 and pH 3 after treatment with neuraminidase and proteolytic enzymes. The
      portion of the dye bound by membrane-negative charge-carriers, as well as by
      hydrophobic interactions with mainly membrane protein compounds, is calculated.
      It is demonstrated that not only the sialic acid, as the main negative charge
      domain, but also proteins are interacting with the dyestuff. Proteolytically
      split membrane fragments contain a considerable amount of alcian blut that cannot
      be associated with the estimated sialic acid content.

PMID- 8157211
TI  - Progression of refractory anaemia with ringed sideroblasts (RARS) to B-acute
      lymphoblastic leukaemia.
AB  - The study describes progression of refractory anaemia with ring sideroblasts
      (RARS) of 3 years' duration to B-acute lymphoblastic leukaemia (ALL). Development
      of ALL in this patient was preceded by the deterioration of dyserythropoiesis,
      leukopenia and an increase of blasts in the bone marrow. Our case may represent
      an additional evidence to the hypothesis that a primary pathogenetic lesion in
      myelodysplastic syndrome occurs at the level of the pluripotent stem cell.

PMID- 8157212
TI  - Granuloblastic masses in the breast: report of two cases.
AB  - Two patients with granuloblastic masses of the breast, onsetting at diagnosis and
      as first relapse site of acute myeloid leukemia are reported. The first case had
      been diagnosed initially as a carcinoma, and the patient underwent bilateral
      mastectomy. Acute leukemia was only revealed by histology of the surgical
      specimen. In the second case a second neoplasia, occurring during acute leukemia,
      was suspected: a fine needle aspirate of the breast mass showed a leukemic
      infiltrate. Involvement of breast during acute myeloid leukemia is a rare event
      and, in our experience, of bad prognostic significance. Mammary glands may be a
      sanctuary for leukemic cells, contributing to unresponsiveness to
      chemotherapeutic agents.

PMID- 8157213
TI  - A guide to ethical conduct in transfusion medicine.

PMID- 8157214
TI  - Study of sodium saccharin co-carcinogenicity in the rat.
AB  - A co-carcinogenicity experiment was conducted with female Sprague-Dawley rats in
      which the effects of short-term sodium saccharin dosing and initiation with a
      direct-acting carcinogen were examined in the urinary bladder. All initiated
      animals were administered 0.5 mg N-methyl-N-nitrosourea (MNU) by instillation
      into the bladder at 8 wk of age. The animals were also given saccharin at one of
      four levels in the diet (0, 1.0, 2.5 or 5%) for 4 wk either (1) just before
      treatment with MNU (4-8 wk of age), (2) centred on treatment with MNU (6-10 wk of
      age) or (3) after MNU treatment (8-12 wk of age). Additionally, a group of
      animals was exposed to saccharin through the milk for 3 wk by dosing the mothers,
      starting on the day of parturition. The animals were held on control diet until
      interim killing of 20 animals per group at about 590 days of age, removal for
      morbidity, or terminal killing of the remainder of 60 animals per treatment
      around 780 days of age. A histopathological examination was made of the urinary
      tract and the relationship of saccharin dose to bladder tumour prevalence
      analysed statistically. A consistent increase (with very weak statistical
      significance) in tumour rate at interim killing, and for the pathology data
      overall, was shown by the 2.5% dose group given saccharin from 8 to 12 wk of age.
      Tumour prevalences of 47.6 and 40.7% v. control prevalences of 21.1 and 25.4%
      were observed for the two time periods (P values < 0.076 and < 0.0853,
      respectively). All groups given saccharin neonatally showed increased tumour
      prevalence for both time periods, but none of the differences was statistically
      significant at the 95% confidence level. No consistent increase in tumour
      prevalence was seen in the groups given saccharin from 4 to 8 or 6 to 10 wk of
      age; thus, these data suggest that saccharin does not act as a strong co
      carcinogen in the MNU-treated rat bladder.

PMID- 8157215
TI  - Dose response of promotion by butylated hydroxyanisole in chemically initiated
      tumours of the rat forestomach.
AB  - The antioxidant food preservative butylated hydroxyanisole (BHA) was tested in an
      initiation-promotion protocol in which male F344 rats (6 wk old), 27 per group,
      were gavaged with a single dose of 200 mg N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG)/kg. After 3 wk on control diet, test diets containing 0, 60, 300, 1000,
      3000, 6000 or 12,000 ppm BHA were fed until termination of the experiment at
      approximately 110 wk, at which time most animals had died with stomach tumours.
      MNNG caused a high incidence of tumours in the glandular stomach and forestomach
      of all groups. Administration of 12,000 and 6000 ppm BHA, but not 3000 ppm or
      lower doses, caused statistically significant increases in the time-related
      incidence of MNNG-induced forestomach tumours as analyzed by life table analysis.
      BHA had no effect on the incidence of tumours in the glandular stomach or
      oesophagus. Tumour incidences in other organs were not related to BHA dose. No
      increase in hyperplasia in the oesophagus was evident in the high-dose BHA
      treated animals compared with the MNNG-only group. This study provides
      corroboration that BHA affects only forestomach tumorigenesis and that the dose
      for enhancement of tumorigenesis is at least 1500-fold greater than human
      exposure.

PMID- 8157216
TI  - Genotoxicity of the alkenylbenzenes alpha- and beta-asarone, myristicin and
      elimicin as determined by the UDS assay in cultured rat hepatocytes.
AB  - While the alkenylbenzenes alpha- and beta-asarone are hepatocarcinogenic in
      rodents, myristicin and elimicin, two other alkenylbenzenes, are not. The present
      study investigated the mechanism of genotoxicity of the asarones to elucidate the
      role of cytochrome P-450 and obtain further information about the relationships
      between the structure, metabolism and genotoxicity of the alkenylbenzenes. The
      data on the ability of these compounds to induce unscheduled DNA synthesis (UDS)
      in hepatocytes derived from male Fischer 344 rats are presented in this paper.
      Cytotoxicity was assessed by lactate dehydrogenase leakage. Elimicin and alpha-
      and beta-asarone are genotoxic in the UDS assay but myristicin is not. The
      genotoxicity of the asarones is inhibited by the cytochrome P-450 inhibitor
      cimetidine but the sulfotransferase inhibitor pentachlorophenol (PCP) is without
      effect. The major metabolite of the asarones in hepatocytes was identified by
      liquid chromatography-mass spectrometry as 2,4,5-trimethoxycinnamic acid but this
      was not genotoxic when tested separately. Simple allylbenzenes such as safrole,
      estragole and methyleugenol are activated by sequential 1-hydroxylation and
      sulfation, and this is the likely mechanism of the genotoxicity of elimicin. The
      propenyl analogues isosafrole, anethole and methylisoeugenol, which cannot
      undergo 1-hydroxylation, are not genotoxic. The positive results obtained with
      the asarones suggest the occurrence of a novel activation 'option' for
      alkenylbenzenes which features a 2-methoxy group in the aromatic ring.

PMID- 8157217
TI  - 2-year carcinogenicity study in the male NMRI mouse with 2-ethylhexyl acrylate by
      epicutaneous administration.
AB  - A 2 yr carcinogenicity study of 2-ethylhexyl acrylate (2-EHA) was conducted by
      applying 25 microliters 21.5, 43 or 85% 2-EHA or 0.015% benzo[a]pyrene (B[a]P) in
      acetone, three times/wk, to the clipped dorsal skin of male NMRI mice (80 per
      group). A further group received acetone and served as the vehicle control. After
      about 7 months of treatment, half of each group was rested from treatment for a
      period of 2 months, then treated with the promoter 12-O-tetradecanoylphorbol-13
      acetate (TPA) for 20 wk followed by observation until termination of the study.
      The other half of each group received continuous treatment with 2-EHA, B[a]P or
      acetone, respectively, for 2 yr. Signs signs of skin irritation were apparent in
      all groups treated with 2-EHA [hyperkeratosis, hyperplasia (acanthosis), crust
      formation and ulceration]. In the group treated with B[a]P alone or B[a]P with
      TPA, 79% and 67% of the mice, respectively, bore squamous cell carcinomas. None
      of the mice treated with acetone or 2-EHA alone developed a skin tumour at the
      application site. One squamous cell papilloma occurred in each of the groups
      treated with 2-EHA and TPA, an incidence matched by the single squamous cell
      papilloma in an untreated area of an acetone control mouse. Thus, 2-EHA proved
      not to be carcinogenic in the skin of male NMRI mice by epicutaneous
      administration.

PMID- 8157218
TI  - Dietary two-generation reproduction study of thiabendazole in Sprague-Dawley
      rats.
AB  - The potential reproductive toxicity of the fungicide and anthelmintic
      thiabendazole (TBZ) was assessed in Sprague-Dawley rats for two generations.
      Doses of 10, 30 or 90 mg/kg/day were administered by way of the diet beginning at
      8 wk of age for the F0 generation and postnatal wk 4 for the F1 generation and
      continuing until the animals were killed. Concentrations of TBZ in the diet were
      adjusted weekly, except during the gestation and lactation intervals when
      concentrations were held constant. There were no TBZ-related deaths or adverse
      physical signs during the study. TBZ-related effects consisted of decreases in
      average body weight gains and food consumption in the middle and high dose
      groups. In both the F0 and F1 generations during the premating and post
      cohabitation periods, the effects in the middle-dose group were observed only in
      males and were generally slight in magnitude (food consumption 3-5% below
      control, weight gain 7-18% below control), whereas the effects in the high dose
      group occurred in both sexes and were slight to moderate in magnitude (food
      consumption 9-13% below control, weight gain 13-46% below control). During
      gestation of the F0 females there were slight decreases in average weight gain
      and food consumption (8% and 4-16% below control, respectively); a similar effect
      on food consumption, but not weight gain, occurred in the F1 generation. There
      were no effects on F0 or F1 reproductive performance (including indices of
      mating, fecundity, fertility, length of gestation, litter size, birth weight, and
      post-implantation survival), nor were any histomorphological changes observed in
      the reproductive tissues of animals in the high dose group. There was no evidence
      of developmental toxicity in the TBZ-exposed F1 or F2 generations, except for
      slight decreases in average pup weights between postnatal days 4 and 21 in the
      high dose group (5-10% below control). The NOAEL (no-observed-adverse-effect
      level) for all developmental, growth, survival and reproductive performance
      parameters assessed in this study was 10 mg/kg/day.

PMID- 8157219
TI  - Effect of ethanol and vitamin A excess on vitamin A status in the liver, plasma
      and foetuses of pregnant rats.
AB  - The effect of maternal consumption of dietary ethanol and high doses of vitamin A
      by gavage was investigated by evaluating plasma, liver and foetal vitamin A in
      Osborne-Mendel pregnant rats with a view to assessing whether ethanol modulated
      the potential toxicity of excess vitamin A. All groups received 4000 IU vitamin
      A/litre in a liquid diet. Ethanol-exposed groups also received 6.4% (v/v) ethanol
      in the liquid diet. Vitamin A was administered by gavage once per day in corn oil
      in doses ranging from 10,000 to 160,000 IU/kg body weight. Plasma vitamin A
      levels in ethanol-exposed groups were similar to levels in a pair-fed group.
      Plasma vitamin A levels were similar in the group given ethanol plus 40,000 IU
      vitamin A/kg and the group given 40,000 IU vitamin A/kg only, but were higher in
      the group receiving ethanol plus 80,000 IU vitamin A/kg than in the group given
      80,000 IU vitamin A/kg only. Retinyl esters were present in the plasma of animals
      receiving 160,000 IU vitamin A/kg only, indicating possible saturation of the
      liver with vitamin A. Retinyl palmitate levels in female foetuses of the group
      administered ethanol plus 80,000 IU vitamin A/kg were significantly higher than
      those of the group administered 80,000 IU vitamin A/kg only; no significant
      differences in levels of retinyl palmitate in male foetuses were observed between
      these two groups. This observation suggests a possible sex difference in the
      modulation of vitamin A toxicity by ethanol in the foetus.

PMID- 8157220
TI  - Mineral interactions in rats fed AIN-76A diets with excess calcium.
AB  - The effects of moderate increases in dietary calcium on maternal and foetal
      mineral interactions were studied in Charles River CD/VAF Plus rats. Female rats
      were given 0.50, 0.75, 1.00 or 1.25% dietary calcium as calcium carbonate in AIN
      76A diets for 6 wk before mating, during mating and for 20 days of gestation.
      Inductively coupled argon plasma-atomic emission spectrometry was used to
      determine mineral levels in the tissues of non-pregnant rats after 42 days on the
      diets, in the tissues of pregnant rats on day 20 of gestation and in the whole
      body of day-20 foetuses. The femurs of the non-pregnant and pregnant rats had a
      dose-related linear increase in calcium content. In livers of the non-pregnant
      rats, dose-related linear increases in the phosphorus, zinc and magnesium content
      were observed, but there was a dose-related decrease in the iron content. There
      were dose-related linear decreases in the iron and copper contents of the kidneys
      from the non-pregnant rats. In pregnant rats dose-related linear decreases were
      observed in the iron content of the liver and in the zinc, iron and magnesium
      contents of the kidney. The foetuses from rats given a moderate increase in
      dietary calcium had dose-related decreases in the whole-body contents of
      phosphorus, iron, copper and magnesium.

PMID- 8157221
TI  - Effect of addition of dried healthy or diseased parsnip root tissue to a modified
      AIN-76A diet on cell proliferation and histopathology in the liver, oesophagus
      and forestomach of male Swiss Webster mice.
AB  - Umbelliferous crop plants, including the parsnip (Pastinaca sativa L.), elaborate
      enhanced levels of furocoumarins, including psoralens, when subjected to biotic
      or abiotic stress. These furocoumarins are recognized to lead to phototoxicity.
      In this study, the effect of these agents, which are present in diseased parsnip
      root tissue, on the liver and two tissues on the route of entry to the body (the
      oesophagus and forestomach) were investigated. Young male Swiss Webster mice were
      fed for approximately 30 days with modified AIN-76A diets containing 32.5% dried
      healthy, 32.5% apparently healthy or 32.5% fungicide-treated parsnip root tissue,
      and 8, 16 or 32.5% dried diseased (Phoma complanata-infected) parsnip root
      tissue. As controls, three modified AIN-76A diets differing in their edible
      starch-to-sucrose ratios (C1-C3) were administered for an equal time. Dried
      healthy parsnip root tissue, compared with controls, did not significantly affect
      any of the indices of cellular proliferation or histopathological parameters that
      were assessed. Histopathological examination of the oesophagus and forestomach
      demonstrated no significant changes as a result of feeding any of the diets
      containing parsnip tissue. In the liver, the highest level (but neither of the
      two lower levels) of dried diseased parsnip root tissue led to swelling of the
      cytoplasm in cells surrounding the central vein of hepatic lobules, with
      consequent compression of the peripheral cells. Using [3H]thymidine
      radioautography, a dose-related increase in cell labelling with the level of
      diseased parsnip root tissue was demonstrated in the liver. Compared with control
      diet C2 only, the extent of [3H]thymidine labelling in the liver was increased in
      mice receiving apparently healthy parsnip tissue; a slight, not statistically
      significant, increase was also noted with fungicide-treated parsnip tissue.
      Increased [3H]thymidine labelling with the feeding of diseased parsnip tissue was
      also found in the greater curvature of the forestomach and the region of the
      oesophageal-forestomach junction, but not at the glandular junction of the
      forestomach nor in the mid-oesophagus.

PMID- 8157222
TI  - Identification of an active principle in essential oils and hexane-soluble
      fractions of Curcuma xanthorrhiza Roxb. showing triglyceride-lowering action in
      rats.
AB  - Curcuma xanthorrhiza Roxb. (C. xanthorrhiza), known as temu lawak or Javanese
      turmeric, has been traditionally used in Indonesia for food and medicinal
      purposes. As little attention has been focused on the role of C. xanthorrhiza in
      lipid metabolism, the hypotriglyceridaemic activity and the active principles of
      the essential oil and hexane-soluble fractions prepared from C. xanthorrhiza were
      investigated in rats. The major component (approx. 65%) of the essential oil was
      identified as alpha-curcumene by capillary gas chromatography/mass spectrometry.
      Addition of essential oils (0.02%), prepared by steam distillation, to a purified
      diet resulted in a lower hepatic triglyceride concentration without influencing
      the serum triglyceride, whereas addition of the hexane-soluble fraction (0.5%)
      resulted in a lower concentration of serum as well as liver triglycerides. Rats
      fed the essential oil and hexane-soluble fraction had lower hepatic fatty acid
      synthase activity. The fraction containing alpha-curcumene, prepared from the
      hexane-soluble fraction by silica gel column chromatography, suppressed the
      synthesis of fatty acids from [14C]acetate in primary cultured rat hepatocytes.
      Thus, alpha-curcumene is one of the active principles exerting triglyceride
      lowering activity in C. xanthorrhiza.

PMID- 8157223
TI  - Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in
      the rat liver.
AB  - Male Wistar rats were fed a control diet or the control diet supplemented with 1%
      (by weight) turmeric for 10 wk. In rats injected with 30 mg Fe2+/kg body weight,
      lipid peroxidation was 29 and 35% lower in liver homogenates and microsomes,
      respectively, of turmeric-fed rats than in those of rats fed the control diet.
      The activities of superoxide dismutase, catalase and glutathione peroxidase were
      higher (by 19, 19 and 20%, respectively) in liver homogenates of rats fed the
      turmeric-containing diet in comparison with the controls. These studies indicate
      that dietary turmeric lowers lipid peroxidation by enhancing the activities of
      antioxidant enzymes.

PMID- 8157224
TI  - Release of lead from crystal decanters under conditions of normal use.
AB  - The pattern of release of lead (Pb) from crystal was investigated using new and
      used decanters. Two decanters in use prior to this study yielded significantly
      less Pb into sherry than did a decanter during its initial use. Pb concentrations
      in sherry after storage for 2 months reached 50, 163 or 1410 micrograms/litre in
      decanters previously used for 20, or for 10 yr, or a new decanter, respectively.
      The new decanter imparted progressively less Pb through normal use. Pb
      concentration was assayed in sherry during a series of three separate sampling
      periods, each 2 months in duration. The Pb concentration at the end of each
      period was 1410, 330 or 150 micrograms/litre respectively. These data are
      consistent with ceramic chemistry theory, which predicts that leaching of Pb from
      crystal is self-limiting exponentially as a function of increasing distance from
      the crystal-liquid interface. The results of this investigation support the
      concept that sufficient ageing of Pb crystal prior to use reduces, to acceptable
      levels, the human health risk to adults associated with consumption of beverages
      stored in Pb crystal decanters.

PMID- 8157225
TI  - The identification of chemicals with sensitizing or immunosuppressive properties
      in routine toxicology.
AB  - In the context of this paper, immunotoxicity is taken to encompass
      immunosuppression/immunopotentiation and allergy. Over the last 10 to 15 years,
      well characterized methods for the assessment of altered immune competence have
      been reported. This has led to proposals for tiered testing schemes. This review
      examines the suitability of immunotoxicity parameters for inclusion in routine 28
      day studies and comments on methods that have been proposed for incorporation
      within the guidelines issued by the US FDA and US EPA and OECD. It is recommended
      that the existing OECD Guideline 407 is modified to incorporate total and
      differential blood cell counts, spleen and thymus weight and histopathology, and
      draining and distal lymph node histopathology for Tier I level testing. Data so
      generated will provide a reliable and accurate means of identifying at an early
      stage potential immunotoxic effects. Tier II testing should be carried out on a
      case by case basis and only assuming positive results are obtained at Tier I. An
      increasingly sophisticated understanding of the nature of immune responses to
      chemical allergens has facilitated the design of novel predictive methods for the
      identification of sensitizing activity. Opportunities which arise from these new
      developments in allergy testing such as the local lymph node assay, mouse ear
      swelling test, and the mouse IgE test should be monitored closely.

PMID- 8157226
TI  - Demonstration of oxidation dyes on human hair.
AB  - This paper describes a method of selected ion monitoring (SIM) analysis which can
      demonstrate the staining of human hair with oxidation hair dyes. Hair samples
      were decomposed with NaOH-Na2S2O4 solution by heating (100 degrees C, 30 min) in
      a stream of nitrogen. Basic and neutral ether extracts from the reaction mixture
      were trifluoroacetylated with trifluoroacetic anhydride in ethyl acetate and were
      then analyzed by SIM. The minimum lengths of a single hair for the detection of
      the 5 components of oxidation hair dyes acting as indicators were 1 mm for
      toluene-2,5-diamine, 2 mm for p-phenylenediamine, 20 mm for p-aminophenol, 50 mm
      for m-aminophenol and 100 mm for o-aminophenol. This method was applied to
      practical cases and the results were good.

PMID- 8157227
TI  - Imaginary constructions and forensic reconstructions of fatal violence against
      women: implications for community violence prevention.
AB  - The almost exclusive media focus on political violence in South Africa has
      deflected attention from the high levels of interpersonal violence in areas of
      socioeconomic deprivation. In order to explore the tension between an at-risk
      community's perspective and the current reality of violence against women,
      imaginary constructions of their own violent death produced by 45 African female
      interview respondents were examined in conjunction with forensic data relating to
      73 African female homicide victims in Cape Town, South Africa. The prototypical
      account of an imagined homicide involved a female commuter being approached by a
      group of men, taunted and assaulted, raped and then killed. The majority of
      actual homicides occurred at or in the vicinity of the residence of the victim,
      with the attacker being known to the deceased. Whilst only 1 of the imagined
      homicide narratives depicted the use of alcohol by the victim, over half the
      actual homicides had elevated postmortem blood alcohol levels. These and other
      disjunctions and convergencies between lay and forensic constructions of violent
      female death should be viewed in the wider context of enmeshment in social
      circumstance, and could provide some understanding of how at-risk communities
      perceive violence against women, thereby providing a foundation for appropriate
      prevention programmes.

PMID- 8157228
TI  - A non-invasive method for postmortem temperature measurements using a microwave
      probe.
AB  - The use of the Microwave Thermography System in Forensic Medicine for the
      estimation of the post-mortem interval is explained. The Microwave Thermography
      System, a new device which is applied to this field for the first time, is
      described and its mode of operation is discussed. The main advantage of using
      this device for estimating the time after death is its ability to measure
      internal body temperatures by a non-invasive method. Using this device, it is
      possible now to measure temperatures of internal organs of the body by placing
      the sensory elements on the skin. Reliability of the system and factors affecting
      the accuracy of post-mortem temperature measurements have been assessed and
      discussed.

PMID- 8157229
TI  - Postmortem release of amitriptyline from the lungs; a mechanism of postmortem
      drug redistribution.
AB  - An experimental rat model was used to study postmortem redistribution of
      amitriptyline (AMI). Two hours after a subcutaneous injection with 20 mg of
      amitriptyline, the rats (n = 40) were anaesthetized and blood samples were drawn
      from the femoral vein and the heart. The rats were then sacrificed by CO2 and
      left at room temperature for either 0.1, 1, 2, 5, 24, 48, or 96 h. Postmortem
      blood samples from the heart and the inferior vena cava, and tissue samples from
      the lungs, heart, liver, right kidney, thigh muscle, the wall of the abdominal
      vena cava and brain were analyzed by high performance liquid chromatography. A
      significant increase was observed within 2 h postmortem in heart blood and later
      also in blood from the inferior vena cava. At 96 h postmortem the concentration
      increase was 4.4 +/- 0.5-fold (P < 0.01) and 3.0 +/- 1.1-fold (P < 0.05) as
      compared to the antemortem values observed in heart blood and blood from the
      inferior vena cava, respectively (mean +/- SEM). In the lungs there was a fall in
      the concentration of AMI from 148 +/- 16.7 mumol/kg at 0.1 h to 49.1 +/- 7.8
      mumol/kg at 96 h postmortem (P < 0.01). In the vessel wall of the abdominal vena
      cava there was also a significant fall in drug concentration, while in heart
      muscle and liver an increase in drug concentration was observed. In animals where
      the lungs were removed agonally (n = 7), the drug concentration in heart blood
      had increased significantly less at 2 h postmortem.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8157230
TI  - The detection of petechial haemorrhages of the conjunctivae in dependency on the
      postmortem interval.
AB  - Petechial haemorrhages of the conjunctivae are not specific for lethal throttling
      or strangulation, but they belong to the important indicators for such
      mechanisms. In experimental models it is shown that petechial bleedings of the
      conjunctivae disappear with the occurrence of advanced signs of putrefaction or
      in cases of fresh-water logging. Therefore, it must be emphasized that the lack
      of petechial haemorrhages in putrefied or fresh-water-logged corpses is of very
      restricted meaning for the examination, whether throttling or strangulation has
      taken place or not, and the autopsy should always be performed in these cases
      with special regard to the neck.

PMID- 8157231
TI  - Traffic deaths in western Norway. A study from the county of Hordaland 1986-1990.
AB  - A series of 133 deaths in traffic in Western Norway has been analysed. There were
      116 deaths from accidents, 14 natural deaths and 3 suicides. Ischemic heart
      disease was the predominant cause of natural death behind the wheel. Single
      vehicular accidents was the predominating accident type and young males were the
      most common victims. Influence of alcohol contributed to a substantial number of
      the accidents. Injuries were classified according to the Injury Severity Scale;
      the higher age victims had a lower ISS score than the young.

PMID- 8157233
TI  - [Radiological survey imaging of the dentition: dental CT versus
      orthopantomography].
AB  - In this study 15 patients with abnormalities in dentition and jaws were analysed
      by computer tomography for the purpose of determining the diagnostic value of
      dental CT scanning in relation to orthodontic problems. The dental CTs were then
      compared with conventional panoramic x-rays. After describing principles and
      methodology, the study discusses the possibilities for clinical applications. The
      study demonstrated that dental CT scanning is definitely superior for diagnosing
      dentition disturbances, for metrical analysis of maxillary antrum relations, and
      for examining bony jaw structures. However, the routine use of dental CT scanning
      as a diagnostic method is at this time constrained due to the relatively high
      amount of time and labour the procedure requires with resulting implications for
      cost factors.

PMID- 8157232
TI  - [The course and results of the orthodontic treatment of 44 consecutively treated
      Class-II cases].
AB  - In this study treatment progress and treatment results of a consecutively treated
      group of 44 patients displaying a Class II malocclusion were evaluated in their
      relationship to the treatment goal. 41% of the patients had come to see the
      orthodontist on the advice of their family dentist but without any subjective
      problems as regards their tooth position. In 43% of the patients the treatment
      could not be finished in accordance with the treatment plan. In approximately 2/3
      of these cases the reasons for the compromised results were due to patient
      cooperation problems. In the other 1/3 various types of treatment problems were
      encountered with loss of anchorage being the most typical. Over the entire
      treatment period patient cooperation was good in only approximately 50% of the
      cases. Oral hygiene was good in 27% of the patients at the first consultation
      appointment, but during the course of treatment this percentage increased to 64%.
      85% of the patients expressed satisfaction with treatment results, but 34% of the
      patients did find the treatment to have been a burden. Enamel decalcifications
      were noticed in eleven patients. In another eleven patients root resorption of
      more than 2 mm of at least one upper incisor was noted.

PMID- 8157234
TI  - [The diagnosis and orthodontic relevance of anterior disk displacement without
      reduction. Clinical, axiographic and magnetic resonance tomographic studies].
AB  - Magnet resonance imaging was used to diagnose 24 temporomandibular joints of 18
      patients as having anterior disk displacement without reduction. By comparing
      clinical functional analysis, axiography, and magnet resonance imaging it was
      demonstrated that a valid diagnosis could be made on the basis of magnet
      resonance imaging alone. Former joint clicking and limitation and a dental Angle
      Class II were diagnostic indications of a disk displacement without reduction.
      Because of often only slight clinical symptoms or their absence, there is always
      a danger that disk displacement without reduction will go undiagnosed. In
      relation to orthodontic therapy, such patients are at risk, because pain can
      arise during treatment.

PMID- 8157235
TI  - [Orthodontic materials studied in the HET-CAM test for mucosa-irritating
      effects].
AB  - A total of 33 different substances used in orthodontic therapy were investigated
      for their potential to irritate mucous membranes. As an alternative to animal
      testing, the HET-CAM test (Hens Eggs Chorioallantois Membrane Test) was employed.
      The effects of the substances on the vessels of the chorioallantois membrane,
      such as haemorrhage, lysis, and coagulation, were videotaped and evaluated. When
      polymerized correctly in accordance with manufacturers' instructions, plastic
      materials used for removable orthodontic appliances and bracket bonding caused no
      irritation. Liquid primers for bracket bonding and monomer substances were highly
      irritating. Etching gels for decalcification of the enamel surfaces were far less
      irritating than liquid etching substances. Thus, primers should be handled with
      care; the use of liquid monomers should be avoided in the oral cavity; and
      etching gels should be preferred to liquid etching substances.

PMID- 8157236
TI  - [Retraction of the upper incisors with pseudoelastic treatment elements. Their
      computational and biomechanical testing and clinical use].
AB  - Based on the favorable results achieved by the application of pseudoelastic T
      loops in the course of canine retraction, this study investigates their
      application to the retraction of maxillary incisors. A modified Burstone T loop
      was made of a pseudoelastic orthodontic nickel titanium wire and then subjected
      to experimental testing. The results obtained were compared with extensive
      numerical studies. The results of the tests showed that forces and moments
      generated by the T loop are suitable for the retraction of upper incisors. The
      clinical application of the pseudoelastic spring was performed using an
      individualized retraction arch enclosing the whole front segment. Whereas during
      canine retraction the experimental and clinical results corresponded very well,
      such was not observed during the retraction of upper incisors. This result
      implies that the location of the center of resistance of the upper incisors has
      not been completely clarified. It is thus recommended that this matter should be
      given further study.

PMID- 8157238
TI  - [Present situation and problems of nosocomial infection].
AB  - Nosocomial Infection goes against treatments, causing unfavorable effects on the
      patients, such as death, delay of job comeback and increase of expenses. The
      rapid progress of medical treatment has been saving many lives, however, the
      number of infected patients has also increased and due to the aging of the
      society, the number is growing. As a result, we see an increasing tendency of
      opportunistic infections by weak toxic pathogens lately. Persons and things in
      hospitals are increasingly becoming the key to elucidate pathogens and route of
      nosocomial infections. Especially MRSA, a normal flora, is a matter of all the
      people related to the hospitals, therefore, all the doctors, nurses and the other
      medical staffs have to deal with the problem. In many medical facilities, a
      committee for control of nosocomial infection is established to take counter
      measures to prevent the infection. In this symposium, present situation and
      problems of nosocomial infection were discussed from each point of view. As a
      result, the most important thing and the first step to deal with this problem is
      a routine washing of hands.

PMID- 8157237
TI  - [Individual variability in the duration of the second phase of the mixed
      dentition].
AB  - With a collection of dental casts from a longitudinal study of 175
      orthodontically untreated probands (100 children without and 75 children with
      premature loss of deciduous molars and/or canines) serving as a base, the
      duration of the second period of mixed dentition was determined to be in relation
      to the probands the period of time between the gingival emergence of the first
      permanent buccal tooth and the full eruption of the set of teeth. The second
      period of mixed dentition in boys without premature loss of deciduous molars and
      canines lasts on an average 3.6 +/- 1.1 years and in girls 3.8 +/- 1.0 years. In
      cases of premature loss of deciduous molars and/or canines, the period of
      dentition is distinctly longer than under normal development conditions. The
      outside parameters (boys: Xmin = 0.9 years, Xmax = 6.2 years; girls: Xmin = 2.6
      years, Xmax = 8.6 years), reflect a high degree of variability. The duration of
      the second period of mixed dentition is significantly affected by "the point in
      time of inception" and by the criteria "morphologically intact support zones" and
      "premature loss of deciduous molars and/or canines". Even given such data,
      however, it is not possible to make a sufficiently reliable prediction on an
      individual basis of the duration of the dentition.

PMID- 8157239
TI  - [Nosocomial infections and infection control committee].
AB  - The problems of nosocomial infections include cross infections from the
      environments to patients in the wards and infections from virus-contaminated
      bloods into medical staffs by mainly needle stick injury. The infection control
      committees organized in Hokkaido University Hospital in 1981 for HBV infection,
      in 1992 for MRSA and HIV infections, provide adequate and urgent advice to all
      the medical staffs to prevent the spread of cross infections and to prevent the
      contaminations of blood-borne viruses. In this report, the present status of
      nosocomial infections especially the opportunistic infections in compromised
      hosts and the role of infection control committees were discussed.

PMID- 8157240
TI  - [Hospital infection in pediatric patients].
AB  - Hospital (nosocomial) infection means infection acquired by patients while they
      are in hospital, or by members of hospital staff. It will occur in modes of three
      categories; 1) cross-infection (infection acquired in hospital from other people,
      either patients or staff), 2) self-infection (infection caused by microbes which
      the patient carries on normal or infected areas of his own body) and 3) self
      infection after acquisition of hospital pathogens from other people or the
      environment. Examples of hospital infections, that we experienced, were presented
      as follows; cross-infection due to gram-negative organisms as Pseudomonas
      aeruginosa and Acinetobacter in neonatal intensive care unit, cross-infection due
      to viruses as RS in infants with cardiovascular diseases and varicella in
      immunocompromised patients, and self-infection supervening cross-infection due to
      potential pathogens including MRSA in immunocompromised children as patients with
      malignant blood diseases and surgeries. The most important preventive measure for
      cross-infection would be isolation of the infected or colonized patients and hand
      washing. To prevent self-infection, it is essential to maintain the defensive
      ability of patient including normal flora, and active immunization or
      prophylactic antibiotic treatment will be needed in some patients. Administration
      of antibiotics often permits selection and overgrowth of multiply resistant
      microorganisms and results in serious infections. Therefore, antibiotic policy
      would be mandatory in each hospital.

PMID- 8157241
TI  - [The current epidemics of nosocomial infection in the field of surgery].
AB  - We studied retrospectively the hospital acquired MRSA and Pseudomonas aeruginosa
      infections in patients of surgery field. The causative bacteria of nosocomial
      infections were mainly MRSA and P. aeruginosa. MRSA was mainly cross-infected via
      the route of medical staffs' hands. P. aeruginosa was mainly infected through
      indirect contact by wet hospital environment. Therefore, MRSA nosocomial
      infections can be prevented by washing and disinfecting hand, and disinfecting
      the dry regions of hospital environment around patients with MRSA infection. P.
      aeruginosa nosocomial infections can be prevented by washing and disinfecting
      hands, and disinfecting the wet regions of hospital environment. Urinary
      indwelling catheter must be aseptically managed for preventing the infection.
      These various preventive measures controlled the nosocomial infection by MRSA or
      P. aeruginosa.

PMID- 8157242
TI  - [Conditions and roles of nurse's care for patients treated in nosocomial
      infections].
AB  - The important task in this problem is to lay the main rules for work with
      patients who are treated for nosocomial infection. Each one of the medical staff,
      who are in contact with the infected patient, must be informed about these rules
      and strictly use these rules in his own work. It is important to determine the
      strict schedule of each medical activity and care for patient and insist on
      strict observance of this schedule. We recognize that this is very important
      because the patient is undergoing special care, we have to try to take his mental
      and psychical status on consideration. From this point of view it is important
      considerate approach to the patient. It is essential to monitor and collect all
      laboratory results and also other informations about the patient. We need these
      informations not only for appropriate maintenance of the patient, but also for
      preventing the spread of the infection. For improving the quality of care for the
      patient it is supposed that it is very necessary to have in the department a
      special person-probably specially trained nurse-who will maintain the
      countermeasure, the collection and analysis of the laboratory results. It is also
      important to accomplish this kind of service 24 hours per day. . Of course it is
      clear that the use of specially trained nurses and the use of only disposable
      materials in the care of the patient is very costly, but we can expect economic
      effects in the decrease of occurrence and spread of infections diseases in our
      department and our hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157243
TI  - [Survey or nosocomial infection chiefly due to MRSA in the Sapporo Medical
      University Hospital].
AB  - Nosocomial infection followed by MRSA (Methicillin Resistant Staphylococcus
      aureus) is an important and serious problem in most of the Japanese hospitals.
      Around 70% of S. aureus isolated from patient's samples in Sapporo Medical
      University Hospital are MRSA. As one of measures to reduce the nosocomial
      infection, we consider that it is a first choice to survey the environmental
      conditions which seemingly cause nosocomial infection. In the present paper, we
      report the results in respect of MRSA contamination in our hospital in general,
      and results of coagulase types of MRSA found in patient's samples and that
      obtained from nasal cavity, finger tips of medical staffs (Doctors and Nurses)
      and swabbed materials in the ward floor, patient's lavatory etc.

PMID- 8157244
TI  - [Aspects of disinfectants for control of nosocomial infections].
AB  - Use of disinfectants is regarded as the most important procedure for preventing
      the transmission of nosocomial infections. Because microorganisms exhibit a wide
      range of resistance to disinfectants, it follows that the kinds of microorganisms
      known and the characteristics of selected disinfectants must be consideration.
      Chemical disinfectants can be classified to three categories according to its
      germicidal action, namely, high-, intermediate-and low -level disinfectant. The
      efficacy of disinfection is affected by a number of factors, each of which
      nullify or limit the efficacy of the process. Some of the factors are the organic
      load on the object; the prior cleaning of the object; the type and level of
      microbial contamination; the concentration of and exposure time to the germicide;
      the temperature and pH of the disinfection process. Handwashing is the single
      most important procedure for preventing nosocomial infections. Although plain
      soaps have been shown to be adequate for routine handwashing in the absence of a
      true emergency, antimicrobial handwashing products should be used for handwashing
      before personnel take care of newborns, severely immunocompromised patients and
      patients in high-risk units. It will be possible to reduce the nosocomial
      infection that the use of rationale handwashing technique, motivation and
      knowledge about the importance of handwashing are achieved.

PMID- 8157245
TI  - [The present status and the issues of the nosocomial infection at Asahikawa
      Municipal Hospital].
AB  - The prophylactic strategy against nosocomial infection at Asahikawa municipal
      hospital is discussed. The issues of the prophylactic strategy are; (1)
      Establishment of a bacterial surveillance system and a series of bacterial
      examination at fixed sites in the hospital organized by our own nosocomial
      infection committee. A quick response and a reaction by the committee according
      to the results obtained from a series of bacterial examinations, (2) Education of
      the practical guide of patient care, sterile technique and management method of
      disposed stuffs according to the anti-infection manual, (3) Improvement of the
      health care system for the hospital staffs, and (4) Planning and carrying out of
      the well-designed improvement plan of the hospital environment.

PMID- 8157246
TI  - [Analysis of the 80 kDa antigen in senile plaque amyloid].
AB  - Amyloid deposition is the major hallmark of Alzheimer's disease (AD). Beta/A4
      protein is identified as the major component of amyloid in the brains of AD. But
      all the components of amyloid and the precise mechanism of amyloid formation are
      still unknown. To provide better understanding of amyloidogenesis in AD brain, we
      have established 12 monoclonal antibodies (mcAb's) which immunohistochemically
      reacted with amyloid or amyloid-related structures, and tried to characterize
      these mcAb's. The epitopes, which these mcAb's reacted with, have been studied,
      and 2 of these mcAb's (Az 172/4, Az 520/4) turned out to react with protein of 80
      kDa in brain homogenate or normal human plasma (NHP). Reactive antigen was
      purified from NHP using PEG fractionation, and immunoaffinity column. Amino
      terminus amino acid sequence analysis of purified antigen was performed, and the
      results showed that 80 kDa antigen was identical to SP-40, 40 (or clusterin).
      Immunohistochemical study revealed that various types of senile plaque and
      vascular amyloid were stained with the mcAb's. In addition, fibrous background
      structures were also stained in AD brain. But there were no positive structures
      in control brains. The above observations indicate that SP-40, 40 is expressed
      and deposited in AD brain. This protein is closely associated with amyloid
      deposition. SP-40, 40 seems to play an important role in pathogenesis of amyloid
      formation in AD.

PMID- 8157247
TI  - [Cloning of Xenopus laevis major histocompatibility complex class II beta-chain
      genes].
AB  - The amphibian Xenopus laevis is the most primitive vertebrate in which the major
      histocompatibility complex (MHC) has been identified both at the biochemical and
      functional level. In the present study, cDNA clones for MHC class II beta-chain
      genes of Xenopus laevis were isolated using the polymerase chain reaction. In
      partially inbred animals with the MHC f haplotype, two distinct cDNA clones
      assumed to encode isotypes were identified. The deduced MHC class II beta-chain
      of Xenopus laevis had structures fundamentally similar to those of their
      mammalian counterparts. The overall amino acid sequence identity between Xenopus
      laevis and representative mammalian MHC class II beta-chains was approximately 41
      50%. Sequence comparison of cDNA clones isolated from outbred individuals and the
      partially inbred frog with the MHC f haplotype showed that nucleotide
      substitutions are located primarily in the beta 1 domain and that non-synonymous
      substitutions occur more frequently than synonymous substitutions in the putative
      antigen binding site. This result indicates that, as in mammalian MHC genes, the
      MHC class II beta-chain genes of Xenopus laevis are under positive Darwinian
      selection. Despite the fact that Xenopus laevis is a tetraploid species, its MHC,
      as defined by serology, immunochemistry, and mixed lymphocyte reaction, is
      diploidized. Family studies showed that all MHC class II beta-chain genes
      detectable in the genome of Xenopus laevis segregate with serologically defined
      MHC haplotypes, suggesting that the second, inactivated set of MHC class II beta
      chain genes was either deleted or that their sequences diverged too far to be
      detected by DNA hybridization. Furthermore, a nearly constant number of MHC class
      II beta-chain genes was detectable in most, if not all, Xenopus species with
      various degrees of ploidy. Thus, various polyploid species of Xenopus appear to
      have used a similar strategy to diploidize their MHC genes.

PMID- 8157248
TI  - [Effects of cutaneous mechanical stimulation on plasma corticosterone,
      luteinizing hormone (LH), and testosterone levels in anesthetized male rats].
AB  - Effects of cutaneous mechanical stimulation on plasma corticosterone, luteinizing
      hormone (LH), and testosterone levels were examined in young adult (13-22 weeks
      old) and aged (24-27 months old) male Wistar rats anesthetized with
      pentobarbital. Under the resting condition without somatic sensory stimulation,
      neither plasma corticosterone measured every 15 min between 1430 h and 1630 h nor
      plasma LH and testosterone measured every 30 min between 1400 h and 1730 h
      revealed any significant fluctuations. Nociceptive mechanical stimulation of both
      hindpaws by pinching for 10 min significantly increased plasma corticosterone,
      LH, and testosterone, in young adult rats. Plasma corticosterone was increased
      for one hour following the stimulation. On the other hand, plasma LH was
      increased 30 and 60 min after the cessation of stimulation, while plasma
      testosterone was increased 60-150 min after stimulation. However, innocuous
      mechanical stimulation of both hindlimbs by brushing for 10 min did not
      significantly change either plasma corticosterone, LH, or testosterone. These
      findings indicate that, nociceptive information from skin lead to the increased
      secretion of corticosterone from the adrenal cortex and the increased secretion
      of LH from the anterior pituitary, resulting in an increase in testosterone
      secretion from the testes into the plasma, after emotional factors are eliminated
      by anesthetizing the subjects. In aged rats, the same nociceptive mechanical
      stimulation by pinching significantly increased the plasma corticosterone levels.
      The magnitude and time-course of the response in aged rats were equivalent to
      those in young adult rats. On the other hand, in aged rats, neither plasma LH nor
      testosterone levels were changed by the same nociceptive mechanical stimulation.
      This is in sharp contrast to the increase in both plasma LH and testosterone
      caused by the stimulation of young adult rats. These findings indicate a
      functional dissociation induced by aging between the secretory responses of the
      anterior pituitary, testes on the one hand and the adrenal cortex on the other
      hand, to nociceptive somatic sensory stimulation. Aging does not alter
      corticosterone release from the adrenal cortex to nociceptive somatic sensory
      stimulation, but LH secretion from the anterior pituitary and testosterone
      secretion from the testes to nociceptive somatic sensory stimulation are subject
      to dysfunction with aging.

PMID- 8157249
TI  - [Effects of megadose methylprednisolone therapy on acute spinal cord injury in
      rats].
AB  - Present study was performed to confirm the protective effect of megadose
      methylprednisolone therapy for the posttraumatic spinal cord ischemia. Seventeen
      Wistar-King rats weighing 215-330 g were divided into four groups which were
      normal group (n = 5), injury group treated by saline (control group, n = 4),
      treated by methylprednisolone (MP) 30 mg/kg (n = 4) and treated by MP 60 mg/kg (n
      = 4). Animals were anesthetized aspirating 1.5% Halothane and made epidural
      clipping injury (140 g for 3 seconds) at Th7/8 after laminectomy of Th7,8. Saline
      or MP of which total volume was 1 ml was injected intravenously 30 minutes after
      injury and spinal cord blood flow (SCBF) was measured 2 hours after injury by
      using 14C-iodoantipyrine autoradiography technique. As for normal value of spinal
      cord blood flow, its gray matter is 96.0 +/- 1.5 ml/100 g/min (mean +/- SE), and
      white matter is 22.9 +/- 1.8 ml/100 g/min. In the gray matter, SCBF severely
      decreased in all injury groups as it closed to the injury site, and there was no
      significant difference among these three groups. In the white matter, SCBF
      decreased at the injury site in all injury groups and there was no significant
      difference. From rostral to caudal of the injury site SCBF decreased in MP
      groups, but in the saline group SCBF showed not so much decrease as MP groups at
      adjacent to the injury site and at more than 3 mm caudal to the injury site
      increase of SCBF (hyperemia) was observed. And decrease of white matter SCBF was
      observed in the rostral rather than in the caudal to the injury site in all
      injury groups. SCBF of the white matter adjacent to the injury site was not
      decreased, but preserved within normal range or rather slightly hyperemic. These
      condition may cause the secondary damage in the adjacent spinal cord. It is
      considered that megadose of methylprednisolone, if it is effective for the spinal
      cord injury, would suppress the SCBF of white matter of adjacent to the injury
      site at the acute phase and prevent the progression of secondary damage.

PMID- 8157250
TI  - [Immunocryoultramicrotomy (gelatin embedding and polyvinyl alcohol embedding
      methods): its procedures, usefulness, and limitations--application to human blood
      cells].
AB  - Cryoultramicrotomy applying immunogold staining (immunocryoultramicrotomy) is a
      useful method to demonstrate the localization of antigens in biological
      specimens. Recently, we have developed a modified method for
      immunocryoultramicrotomy using gelatin as an embedding medium (gelatin embedding
      method). In this study, we compared the results obtained by the gelatin embedding
      method with those obtained by a conventional method applying polyvinyl alcohol
      embedding (PVA embedding method). Both methods were easy to perform, and yielded
      fairly satisfactory results in terms of detecting antigens and preserving
      ultrastructures. According to the gelatin embedding method, membranes enclosing
      organelles revealed a negatively stained image, and organelles were clearly
      delineated by an electron-lucent layer. In contrast, a positively stained image
      was obtained by the PVA embedding method; however, the delineation of organelles
      was somewhat inferior to that of the gelatin embedding method. Although these
      methods were useful to detect various biological antigens, they had some
      limitations in sensitivity. Prior glutaraldehyde fixation was requisite for
      cryosectioning and preserving ultrastructures, but it caused the loss of
      antigenicity to some extent. This should be taken into account when evaluating
      the results obtained by immunocryoultramicrotomy. In this paper, we present the
      detailed procedures of the gelatin embedding method, as well as the PVA embedding
      method, and demonstrate the localization of myeloperoxidase, lysozyme and CD3
      molecules in human blood cells using both methods.

PMID- 8157251
TI  - [Comprehensive study on the membrane currents of porcine granulosa cells in
      culture].
AB  - The membrane currents of primary cultured porcine granulosa cells have been
      studied using the whole-cell configuration of the patch-clamp technique. And
      effects of K+ channel blockers upon progesterone production of the cells have
      been also studied. The author has identified and characterized two types of K+
      currents, transient outward current (Ito) and a delayed rectifier K+ current
      (Ik), and Ca2+ current (Ica). Ito and Ik were voltage -and calcium-dependent.
      Both of the currents were blocked by 4-aminopyridine (4-AP), a K+ channel
      blocker, but only Ik was sensitive to tetraethylammonium (TEA), another K+
      channel blocker. Ica was inactivated within 50 ms of the test pulse. Nifedipine
      and verapamil, L-type Ca2+ channel blockers, did not suppress Ica even at a
      concentration of 10 microM. Tetramethrin (1 microM), a T-type Ca2+ channel
      blocker, decreased Ica. These findings suggested that the current was T-type Ca2+
      current. LH and dibutyryl cAMP, potent stimulants of steroid production,
      attenuated Ito by 13.9 +/- 1.8% (n = 7) and 21.0 +/- 1.5% (n = 4), respectively.
      However, they did not affect Ik and Ica. These results indicated that LH did not
      modulate Ca2+ current directly, but it suppressed Ito through cAMP. 4-AP (0.2-5
      mM) suppressed basal and LH-induced progesterone production of porcine granulosa
      cells dose-dependently, but TEA (2-10 mM) did not influence progesterone
      production. These data suggest that Ito may play a role in steroid secretion or
      other functions in granulosa cells.

PMID- 8157252
TI  - [Pollution of fish and shellfish with organotin compounds and estimation of daily
      intake].
AB  - Tributyltin (TBT) and triphenyltin (TPT) compounds have been widely used as
      antifouling paint for ship bottoms and fishery firm nets, and they are known to
      be aquatic environmental contaminants. A survey of the pollution with organotin
      compounds in fish and shellfish has been carried out for samples (180 samples
      from 43 kinds) which were collected in the Hokkaido prefecture during the period
      from February, 1989 to September, 1992. On the other hand, daily intakes of
      organotin compounds have been investigated using the Market Basket Method.
      Relatively high concentrations of TBT and TPT were detected from flat fish and
      shellfish such as Hirame (bastard halibut), Kurogarei (black plaice), Asari
      (Japanese littleneck), Hokkigai (Japanese surf clam) and Kaki (oyster). The
      maximum value of TBT in samples was 0.38 microgram/g (for both Asari and Kaki),
      and TPT was 0.47 microgram/g (Kurogarei). Estimated daily intakes of DBT, TBT and
      TPT were 0.45 microgram, 2.40 micrograms and 4.11 micrograms, respectively. The
      values presented in this study were lower in comparison with the acceptable daily
      intake. It was revealed that the values of the organotin compounds in this study
      were not so high as to have any efect on human health at the present.

PMID- 8157253
TI  - [A new assessment of quality of life (QOL) for cancer patients].
AB  - A new assessment of quality of life (QOL) was made for cancer patients. The QOL
      assessment consists of 12 items: pain; nausea; constipation; general fatigue;
      sleep; eating; activity; a daily life pattern; conversation; treatment
      acceptability; satisfaction at the present status and family exhaustion. Ranges
      of scores are one (best) to five (worst). For visual expression of QOL, the
      author made an original method called "QOL diagram", drawn with a circle which
      has 12 diverging lines marked five points indicating the score for each item. QOL
      changes after cancer pain control with either oral or intravenous morphine were
      examined in 22 adult cancer patients by the QOL assessment. Laxatives and anti
      nausea drugs were mostly prescribed at the same time in order to avoid side
      effects of morphine. QOL was evaluated and recorded by the author through an
      individual interview with each patient. It was observed that the psychological
      factors were improved along with pain relief. Although items such as general
      fatigue, nausea, constipation, sleep and eating did not change considerably at
      first, they improved well with time in the oral morphine group. On the other
      hand, there was no marked time-dependent change in the intravenous morphine
      group. Items such as activity, a daily life pattern and conversation were rather
      negative than positive. These items seem to be more important to improve QOL of
      the cancer patients, in particular, whose general status is relatively good. In
      conclusion, the QOL diagram helped us to follow subtle changes of status and
      needs of cancer patients. And it enables us to easily assess risks and benefits
      of the treatment plans including palliative care and home supportive programs. It
      is designed for both patients and medical staffs to use easily and repeatedly.
      However, the further evaluation and refinement will be needed to verify validity
      and reliability of the QOL diagram before a routine clinical application.

PMID- 8157254
TI  - [Regulation of the complement C3 gene expression: regulatory elements required
      for cytokine-induced expression].
AB  - I isolated murine and human genomic cosmid clones of complement C3 gene and
      sequenced 5'-flanking region of their transcriptional initiation sites to
      determine cis-elements that participate in regulation of C3 gene expression. The
      murine and human 5'-flanking regions are 51% identical overall, with positions 
      36 to -1 and -146 to -68 showing 80% identity. Four TATA boxes were identified
      upstream of the murine transcriptional initiation site, but only the TATA element
      at position -30 is essential for expression of murine C3 in hepatocytes. Deletion
      and transfection analysis indicated that sequences -395 to -111 are essential for
      constitutive expression of C3 gene and suggested that sequences between -1457 and
      -800 contain regulatory elements that are involved in suppressing basal
      expression. Mutation analyses showed that sequences between -88 and -83 are
      essential for IL-6 responsiveness and both sequences between -88 and -83 and -77
      to -72 are necessary for enhancer activity and responsiveness to IL-1. These
      sequences are highly homologous to binding sites of DNA binding proteins, C/EBP
      and NF-kappa B, respectively. Collectively, these results localize cis-acting
      elements involved in constitutive and IL-1/IL-6-regulated murine C3 gene
      expression, and provide implication for specific trans-acting factors.

PMID- 8157255
TI  - [Analysis of the hepatocyte growth factor receptor in regeneration and
      oncogenesis of hepatocytes].
AB  - The Met proto-oncogene product is a tyrosine kinase receptor whose ligand is
      hepatocyte growth factor (HGF). The Met protein is first synthesized in the
      hepatocytes as a single chain precursor, or p170MET proreceptor, and is then
      processed to a mature heterodimer receptor consisting of an extracellular alpha
      subunit (p50 alpha MET) and a transmembrane beta subunit (p 145 beta MET). The
      beta subunit has a protein kinase domain which is activated through
      phosphorylation on tyrosine residue by the binding of HGF to the receptor. In
      order to elucidate the function of the Met gene product in hepatic disorders, we
      analyzed the expression and tyrosine phosphorylation of the Met protein on
      regeneration and carcinogenesis of the liver. For studies on carcinogenesis we
      used human hepatoma tissues, and for studies on regeneration we used rat
      hepatectomy. Two antibodies were used for western blotting; a mouse monoclonal
      anti-phosphotyrosine antibody, which recognizes phosphorylated tyrosine residue
      in proteins, and a polyclonal rabbit anti-Met antibody, which recognizes the C
      terminus of both the Met beta chains and proreceptor. To compare the amount of
      protein in each experiment, the results of western blotting were evaluated using
      an image analyzing system. In experiments involving rats with partial
      hepatectomy, a decreased expression of the proreceptor with a decreased amount of
      tyrosine phosphorylation was observed within 12 hours of hepatectomy. However,
      there were no significant changes of the Met beta subunit during the experiment.
      These data suggest that the Met proreceptor is decreased in the early stages of
      liver regeneration. In experiments on human samples surgically removed from 18
      patients with hepatocellular carcinoma, the met proteins, p 145 beta MET and p
      160 MET proreceptor, were expressed both in cancer tissues (12/18, and 10/18,
      respectively) and in non-cancer tissues (8/18, and 15/18, respectively). From the
      comparative analyses of the intensity of the signals in cancerous region against
      those of non-cancerous region in the 18 individual cases, it was demonstrated
      that expression of p 160 MET proreceptor was increased in non-cancerous region
      more significantly than in cancerous region (p < 0.05). On the contrary,
      expression of p145 beta MET was increased in cancerous region more significantly
      than in non-cancerous region (p < 0.05), except for a few cases of poorly
      differentiated carcinomas in which p 145 beta MET signal was not detected. These
      findings suggested that a processing pathway from the proreceptor to the mature
      Met receptor is amplified in carcinogenesis of the liver.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8157256
TI  - Lipoprotein analysis in transgenic mice expressing human apolipoprotein (apo) A-I
      and apo C III: use of micromethods in analysis of lipoprotein system in mice.
AB  - Transgenic animal technology has added a new dimension to the study of
      lipoprotein physiology. The unique advantage of the technology is that the exact
      physiological role (s) of a gene and the corresponding protein whose function (s)
      has been undefined may be revealed in vivo by the expression or inactivation of
      the expression of the gene. Although mice are most frequently used transgenic
      animals, the lipoprotein system has not been studies extensively. This report
      primarily focuses on practical applications of the existing laboratory methods to
      transgenic mice expressing human apoproteins. Described below is the summary of
      the results obtained from transgenic mice expressing human apo A-I and apo C III.
      In one line of transgenic mice expressing human apo A-I, the total plasma apo A-I
      level (mouse plus human) was higher than that in control (mean +/- SEM, 381 +/-
      18 vs. 153 +/- 7 mg/dl, n = 6, respectively, p = 0.0001) with 64% increase in the
      HDL cholesterol (HDL-C) level (90 +/- 3 vs. 55 +/- 5 mg/dl, p = 0.0001). High fat
      feeding further increased the apo A-I and HDL-C levels. One line of apo C III
      transgenic mice with approximately 100 copies of human apo C III gene were
      severely hypertriglyceridemic compared to negative littermates (mean +/- SEM; 959
      +/- 217 vs. 49 +/- 6 mg/dl). In a second line, animals with one to two copies of
      the human apo C III gene manifested mild hypertriglyceridemia. These experiments
      revealed for the first time in vivo that overexpression of apo A-I and C III
      could lead respectively to hyperalphalipoproteinemia and hypertriglyceridemia and
      may suggest possible etiology for these disorders in human.

PMID- 8157257
TI  - [Depressant effects of volatile anesthetics on second messenger system in mRNA
      expressed Xenopus laevis oocytes].
AB  - In this study I attempted to elucidate the depressant effects of volatile
      anesthetics on inositol trisphosphate (IP3)-mediated signal transduction pathway
      and to identify the site of action. For this purpose, we used Xenopus laevis
      oocytes which translated and expressed 5-HT receptors after injection of mRNA
      isolated from the rat brain. In this system, binding of the agonist to G-protein
      coupled receptors activates phospholipase C that produces IP3. Mobilization of
      Ca2+ by IP3 from the storage finally opens Ca2+ dependent Cl- channels.
      Halothane, isoflurane and methoxyflurane depressed Cl- current elicited by 5-HT.
      For the further quantitative study, methoxyflurane was used because of its better
      solubility and less vapor pressure that avoided evaporation of the agent. The 5
      HT elicited Cl- current was depressed in a non-competitive fashion. Response were
      75, 60, 20% of control in the presence of 0.5, 1 and 3 mM methoxyflurane,
      respectively. Responses elicited by a pressure-injection of Ca2+ or IP3 remained
      unchanged in the presence of high concentrations of either halothane, isoflurane
      or methoxyflurane. These results suggest that the depressant mechanism by
      volatile anesthetics on the signal transduction pathway involves neither Ca2+
      dependent Cl- channel dynamics nor intracellular Ca2+ mobilization by IP3.
      Changes of microdomain characteristics of the membrane in the presence of
      anesthetic molecules including membrane-bound proteins and enzyme system may be a
      main mechanism of action of volatile anesthetics.

PMID- 8157258
TI  - [Polymorphism of the TAP genes Japanese healthy control and type I diabetes
      mellitus].
AB  - Stable cell surface presentation of MHC class I molecules requires active
      transport of antigenic peptides across the endoplasmic reticulum by products of
      two genes, TAP1 and TAP2, which are maped in the MHC class II region. There are
      many human diseases whose onset are associated with particular MHC alleles.
      However it has not always been possible to assign susceptibility to individual
      genes because genes within the complex are in linkage disequilibrium. In this
      study, we tested DNA from sixty-three healthy controls and 64 Insulin Dependent
      Diabetes Mellitus: IDDM patients by Polymerase Chain Reaction-Sequence Specific
      Oligonucleotide: PCR-SSO, Polymerase Chain Reaction-Single Strand Conformation
      Polymorphism: PCR-SSCP analysis and DNA sequencing. These studies demonstrated
      the difference in frequencies of TAP2 gene products between healthy control and
      IDDM patient, and between Japanese and Caucasian population. Statistic analysis
      of HLA antigens and variants amino acids of TAP showed the linkage disequilibrium
      between TAP2-665, -687 sequence and HLA-DR alleles. The data suggests that the
      association of TAP2 allele with IDDM disease may be a simple reflection of the
      linkage disequilibrium between TAP allele and DR4 gene.

PMID- 8157259
TI  - [Treatment and prognostic factors of stage I and II non-Hodgkin's lymphoma].
AB  - In order to assess prognostic factors and therapeutic methods, 104 patients (aged
      6 to 89; mean age 57.4; male 68, female 36; stage: I 45, II 59) with clinical
      stages I and II non-Hodgkin's lymphoma treated at our department between 1977 and
      1991 were reviewed. Factors, such as sex, age, clinical stage, primary site,
      presence of general symptoms, pathology, tumor size, LDH and therapeutic methods
      (radiotherapy alone; initial radiotherapy plus chemotherapy; initial chemotherapy
      plus radiotherapy) were calculated by univariated analysis to determine important
      factors influencing the survival. The survival of patients with symptoms and
      large tumors (more than 70 mm) was shorter than that of those without symptoms
      and with small tumors (5 years survival: symptom B 17.9%, A 68.2%, p < 0.001;
      tumor more than 70 mm 44.0%, less than 70 mm 67.1%, p < 0.05). Regarding
      therapeutic methods, radiotherapy alone achieved a 5-year survival rate of 37.1%;
      initial radiotherapy plus chemotherapy had 64.6% and initial chemotherapy plus
      radiotherapy 78.5%, but a significant difference was noticed only between
      radiotherapy alone and initial chemotherapy plus radiotherapy (p < 0.001). These
      results suggest that important factors influencing the survival are presence of
      general symptoms, tumor size and therapeutic methods.

PMID- 8157260
TI  - Preliminary report on the paleodemography of the K2 and Mapungubwe populations
      (South Africa).
AB  - Paleodemographic studies have seldom been attempted in sub-Saharan Africa. The
      Mapungubwe complex of sites in northern Transvaal (A.D. 970-1200) has yielded
      enough skeletal material to warrant such an investigation. The skeletal
      collection consists of 109 individuals (97 from K2 and 12 from Mapungubwe
      itself). Because the sites are extensive and their complete excavation
      impractical, only reconstruction of the population dynamics, not the population
      size, was possible. There were 81 child and juvenile skeletons (below 15 years of
      age) and 7 male, 5 female, 4 possible male, and 4 possible female adult
      skeletons. Eight adult skeletons were too fragmentary to warrant even tentative
      sex diagnoses. Either age-specific burial practices resulting in the surplus of
      child skeletons, unusual child mortality, or a state of substantial natural
      increase must be the explanation for this age distribution. The hypothesis of the
      natural increase can be partly tested by using an appropriate correction to the
      life table. The life table corrected for r = 2.5% has a newborn life expectancy
      of 18.93 +/- 1.79 years and a survivorship to 15 years of 41.66% +/- 3.91. The
      population pyramid derived from this life table compares well with data on some
      third world populations observed earlier this century. The fertility rate
      required to maintain the natural increase under such mortality conditions is high
      but comparable to that of some historical populations. High positive natural
      increase would indicate an economically successful population.

PMID- 8157261
TI  - Efficacy of a composite biological age score to predict ten-year survival among
      Kansas and Nebraska Mennonites.
AB  - In 1980 and 1981 Mennonite descendants of a group of Russian immigrants
      participated in a multidisciplinary study of biological aging. The Mennonites
      live in Goessel, Kansas, and Henderson, Nebraska. In 1991 the survival status of
      the participants was documented by each church secretary. Data are available for
      1009 individuals, 177 of whom are now deceased. They ranged from 20 to 95 years
      in age when the data were collected. Biological ages were computed using a
      stepwise multiple regression procedure based on 38 variables previously
      identified as being related to survival, with chronological age as the dependent
      variable. Standardized residuals place participants in either a predicted-younger
      or a predicted-older group. The independence of the variables biological age and
      survival status is tested with the chi-square statistic. The significance of
      biological age differences between surviving and deceased Mennonites is
      determined by t test values. The two statistics provide consistent results.
      Predicted age group classification and survival status are related. The group of
      deceased participants is generally predicted to be older than the group of
      surviving participants, although neither statistic is significant for all
      subgroups of Mennonites. In most cases, however, individuals in the predicted
      older groups are at a relatively higher risk of dying compared with those in the
      predicted-younger groups, although the increased risk is not always significant.

PMID- 8157262
TI  - Relationship between body mass index, age, and serum adrenal androgen levels in
      Peruvian children living at high altitude and at sea level.
AB  - We have determined the relationship between body mass index (BMI) and serum
      adrenal androgen levels when age is controlled for in children, aged 7-12 years,
      living in Lima (150 m above sea level) and in Cusco (3400 m above sea level). The
      purpose of the study was to determine whether the relationship of serum adrenal
      androgen levels with both BMI and age differs between low and high altitude. The
      ratio weight/height2 is not an adequate marker of BMI because it correlates with
      height in children from Lima and Cusco. The ratio weight/height2.3 correlates
      with body weight but not with height and was used in the present study as the
      BMI. From age 7 to 12 years, the BMI increased significantly with age only in
      boys from sea level and in girls from high altitude. The study demonstrates that
      serum adrenal androgen levels are not related to BMI in either sea-level or high
      altitude children when the effect of age is removed statistically. These data
      suggest that BMI in children is not related to serum levels of adrenal androgens
      and that delayed age of adrenarche observed in children at high altitude may be
      due to factors other than nutritional status.

PMID- 8157263
TI  - New data for AG haplotype frequencies in Caucasoid populations and selective
      neutrality of the AG polymorphism.
AB  - We present the results of AG antigen typings of three Caucasoid population
      samples: Lebanese, Tunisians, and Finns. AG haplotype frequencies estimated by
      maximum-likelihood methods are compared with the frequencies observed in 13 world
      populations previously tested for AG specificities by computing a genetic
      distance matrix used in a multivariate analysis. A high degree of polymorphism
      characterizes the three samples, with 10 haplotypes detected in the Lebanese and
      11 haplotypes detected in the Tunisians and Finns; high heterozygosity levels are
      also present in the three populations. The genetic distance analysis shows that
      the three populations possess a genetic structure intermediate between those
      observed in sub-Saharan Africans and in Caucasoids from the Near East and India.
      This tight correspondence between AG differentiation and geography is confirmed
      by a highly significant correlation coefficient found between genetic and
      geographic distances computed worldwide, suggesting that an isolation by distance
      model of evolution applies to the AG system. The Ewens-Watterson test for
      selective neutrality on all world populations tested for AG specificities also
      supports the hypothesis that the AG system behaves like a neutral polymorphism.
      Overall, the AG differentiation pattern appears to be close to the patterns
      observed for other serological polymorphisms, such as RH, GM, and HLA, whose
      evolutionary mechanisms are also discussed.

PMID- 8157264
TI  - Is migration kin structured?
AB  - We estimate the strength of kin-structured migration in six human populations
      (five from New Guinea and one from Finland) and in one population of nonhuman
      primates. We also test the hypothesis that migration is not kin structured by
      generating a sampling distribution of the estimator under the null hypothesis of
      independent random migration. We are unable to detect a statistically significant
      level of kin-structured migration in any population. However, five of our six
      human populations were from Papua New Guinea, and we cannot dismiss the
      possibility that migration is kin structured in other parts of the world.

PMID- 8157265
TI  - Religious differentials in postfamine marriage patterns, Northern Ireland, 1840
      1915. I. Demographic and isonymy analysis.
AB  - During the Irish famine of 1846-1851 there were an estimated 1.0 million excess
      deaths, the migration of 1.3 million persons, and 300,000 averted births. To
      assess the influence of population changes at the local level in Ulster,
      decennial census records were analyzed for the Barony of Upper Ards, County Down,
      from 1841 to 1911. Data on marriages contracted in the four Roman Catholic, five
      Presbyterian, and eight Episcopalian congregations also were abstracted from
      civil parish registers for the period 1840-1915 and were used to calculate levels
      of random and nonrandom inbreeding through time by isonymy analysis. In the
      prefamine census of 1841 the total population of the Upper Ards was 16,964. From
      1841 to 1911 population numbers decreased by 44.5%, with a consistent surplus of
      females in all parishes throughout the study period. Both population density and
      the number of persons per dwelling declined at equivalent rates, resulting in
      increasingly dispersed patterns of settlement. There was a marked overall
      increase in nonrandom inbreeding (Fn) in the immediate postfamine period, which
      was sustained throughout the nineteenth century before declining during 1900
      1915. However, significant heterogeneity was observed in the Fn values
      calculated, both between and within each of the three main religious
      denominations, indicating differential local responses to marriage partner choice
      in the postfamine years. The observed changes are not compatible with a simple
      model of reduction in mate availability under conditions of population decline.
      Instead, they can most convincingly be explained in terms of a specific
      population response to the subsistence crisis initiated by the famine.

PMID- 8157266
TI  - Nutrition and the variation in level and age patterns of mortality.
AB  - We examine the associations between nutrition and mortality at the national
      level. Altogether four aspects of this association are explored: (1) total
      calories with expectation of life, (2) dietary composition with expectation of
      life, (3) total calories with the age patterns of mortality, and (4) dietary
      composition with the age patterns of mortality. The data consist of life tables
      and national food balance sheets for 341 populations from 96 countries. A
      preliminary principal components analysis conducted on the dietary composition
      data yields three dietary components: (1) the overall quality and quantity of the
      diet, (2) the relative contribution of carbohydrates versus fats, and (3) the
      relative contribution of fats versus proteins. The results indicate that
      expectation of life at birth increases with total calories, with overall quality
      and quantity of the diet, and with the ratio of fats to proteins. The ratio of
      carbohydrates to fats is negatively associated with level of mortality. However,
      evidence indicates that the main effect of the ratio of fats to proteins is
      reversed when diets are high in quality and that all the effects tend to saturate
      at high nutrient availability. Variation in nutrition is also strongly associated
      with the international variation in age patterns of mortality. For example, when
      expectation of life is held constant, populations with higher quality diets tend
      to have lower childhood mortality and higher adult mortality. The results
      indicate that nutritional patterns are highly correlated with much of the
      worldwide variation in mortality and may be a useful criterion for selecting or
      predicting the best suited model life table for use on a particular population.

PMID- 8157267
TI  - Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine
      response of blood lymphocytes to mycobacterial antigens.
AB  - Proliferation and cytokine production profiles by blood mononuclear cells in
      response to in vitro stimulation with mycobacterial antigens were compared in
      patients with active tuberculosis and in sensitized healthy controls. Interleukin
      4 (IL-4) and interferon-gamma (IFN-gamma) were detected at single-cell level
      using the ELISPOT assay. Patients showed significantly (P < 0.01) increased
      numbers of IL-4-secreting cells and decreased thymidine incorporation, but no
      significant difference in IFN-gamma-producing cells in response to the 38,000 MW
      or 19,000 MW antigens and their immunodominant peptide epitopes. Pronounced
      individual variations were found in both patient and control groups, when
      comparing the responsiveness to the mycobacterial extract, two protein antigens
      and five synthetic peptides. None of the antigens or peptides tested showed
      preferential stimulation of either IL-4- or IFN-gamma-secreting T cells, and
      proliferation was not correlated with either IL-4 or IFN-gamma production. In
      particular, cytokine responsiveness was of similar frequency in subjects who did
      or did not show positive proliferation, indicating that the latter test was not
      fully representative of the active T-cell repertoire. It is concluded that the
      demonstrated Th2 type of profile in response to two prominent mycobacterial
      antigens may play a role in the mechanisms of defective host resistance in
      tuberculosis.

PMID- 8157268
TI  - Effect of IFN-gamma and endogenous TNF on the histopathological changes in the
      liver of Listeria monocytogenes-infected mice.
AB  - During primary infection of mice with Listeria monocytogenes, the bacteria
      proliferate extensively in the liver resulting in the development of inflammatory
      lesions in this organ. In the present study, the effect of interferon-gamma (IFN
      gamma) on the development of these lesions, and the involvement of endogenous
      tumour necrosis factor-alpha (TNF-alpha) in the IFN-gamma-induced effects were
      evaluated. During an infection of naive mice with L. monocytogenes, two types of
      inflammatory lesions in the liver could be distinguished: large necrotic lesions
      consisting of granulocytes and/or exudate macrophages and small lesions
      containing mainly mature macrophages, i.e. BM8-expressing cells. Necrotic lesions
      were characterized by the presence of CD11b-expressing cells and consisted mainly
      of granulocytes during days 1 and 2 of infection and thereafter of exudate
      macrophages. The lesions consisting of mature macrophages and lymphocytes were
      not associated with necrosis and were called granulomatous lesions. Some of the
      granulomatous lesions contained many cells that expressed Ia antigen, i.e.
      activated cells. Treatment of mice with recombinant (r)IFN-gamma before injection
      of L. monocytogenes resulted in a decrease in the number of necrotic lesions and
      an increase in the number of granulomatous lesions in the liver, which was
      accompanied by a reduced bacterial proliferation in the liver. The effect of rIFN
      gamma on the development of the various types of inflammatory lesions in the
      liver during infection with L. monocytogenes was abrogated by anti-TNF-alpha
      antibody and this antibody abrogated the rIFN-gamma-induced reduction of
      bacterial proliferation in the liver as well. Together, the results demonstrate
      that endogenous TNF-alpha plays a key role in the effects of rIFN-gamma on the
      inflammatory response in the liver during an infection with L. monocytogenes.

PMID- 8157269
TI  - Inhibition of allograft rejection by anti-T-cell receptor-alpha beta monoclonal
      antibodies preserving resistance to bacterial infection.
AB  - Anti-CD3 monoclonal antibody (mAb) has been administered in clinical organ
      transplantation to reverse acute allograft rejection; however, severe
      immunodeficiency can result from such mAb treatment and cause an increased
      incidence of opportunistic infections. Therefore, new model systems are required
      in order to establish better methods for suppressing allograft rejection while
      preserving resistance to opportunistic infections. In this study, we compared the
      effects of the in vivo administration of anti-T-cell receptor-alpha beta (TcR
      alpha beta) mAb, H57-597, with those of anti-CD3 mAb, 145-2C11. Much to our
      surprise, the in vivo administration of anti-TcR alpha beta mAb prior to skin
      grafting led to a longer allograft survival than that of anti-CD3 mAb at any of
      the comparable dosages examined. In the lymphoid organs of mice treated with anti
      TcR alpha beta mAb, TcR alpha beta-bearing cells were almost completely depleted,
      while TcR gamma delta-bearing cells remained at a relatively increased level on
      day 14 after anti-TcR alpha beta mAb treatment. The in vitro stimulation by anti
      TcR gamma delta mAb clearly showed that such TcR gamma delta-bearing cells were
      functionally intact. Furthermore, the mice treated with anti-TcR alpha beta mAb,
      but not anti-CD3 mAb, were observed to be resistant to infection with Listeria
      monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a
      marked prolongation of skin allograft survival in the thymectomized mice. These
      results strongly suggest that anti-TcR alpha beta mAb, which partially preserved
      anti-bacterial resistance, may be more effective in preventing graft rejection
      than anti-CD3 mAb in the periphery, and indicate that anti-TcR alpha beta mAb may
      thus be potentially applicable for human transplantation. In addition, these
      results also indicate that the TcR gamma delta-bearing cells alone, at least in
      the absence of TcR alpha beta-bearing cells, do not contribute to allograft
      rejection in vivo.

PMID- 8157270
TI  - Human cytotoxic T lymphocytes stimulated by endogenously processed human
      papillomavirus type 11 E7 recognize a peptide containing a HLA-A2 (A*0201) motif.
AB  - Cytotoxic T lymphocytes (CTL) may play an important role in the control of human
      papillomavirus (HPV)-induced anogenital neoplasias, but have been difficult to
      study owing to the difficulty in obtaining sufficient quantities of infectious
      virus. To address this we have stimulated human HPV-specific CTL in vitro using
      low-density cells (LDC) from peripheral blood mononuclear cells (PBMC). Low
      density cells were used to present synthetic peptides, or endogenously processed
      peptides expressed from recombinant vaccinia viruses, to high-density PBMC
      (predominantly lymphocytes) for 6 days. Cytotoxic T lymphocytes stimulated with
      endogenously processed HPV 11 E7 recognized the synthetic HLA-A2 (A*0201) motif
      containing nonamer, 4-12. In reciprocal experiments, CTL stimulated with this
      peptide in vitro recognized targets expressing endogenously processed E7. The
      responses in each case were A2 restricted and peptide specific. Two additional A2
      motif-containing nonamers from HPV 6b E7 (21-30 and 47-55) also elicited peptide
      specific, A2-restricted CTL. The data illustrate the potential that in vitro
      stimulation with LDC has in understanding CTL responses to experimentally
      problematic viral systems such as HPV, and may offer a route to specific
      immunotherapy of HPV-associated lesions.

PMID- 8157271
TI  - Identification of a putative cellular receptor for feline immunodeficiency virus
      as the feline homologue of CD9.
AB  - A monoclonal antibody vpg15 has been identified which recognizes a putative
      cellular receptor for feline immunodeficiency virus (FIV). The antibody
      immunoprecipitates a single 24,000 MW species from feline cells. The molecular
      size and pattern of expression of the ligand for the vpg15 antibody displayed
      similarities to that of the human leucocyte differentiation antigen CD9. The
      reactivity of the vpg15 antibody was therefore compared with that of the anti
      human CD9 antibody FMC56, an antibody which cross-reacts with feline cells.
      Expression of the vpg15 ligand correlated well with the reactivity of the FMC56
      antibody on peripheral blood leucocytes and a panel of feline cell lines.
      Furthermore, the anti-human CD9 antibody reacted with murine fibroblast cells
      which had been transfected with high molecular weight feline DNA and
      immunoselected with the vpg15 antibody. FMC56 and vpg15 immunoprecipitated a
      similar 24,000 MW species from surface-iodinated feline cells and depletion of
      the vpg15 ligand from cell lysates resulted in a corresponding depletion of the
      FMC56 ligand. The data demonstrate that the vpg15 antibody recognizes the feline
      homologue of human CD9 and implicate feline CD9 as a cellular receptor for FIV.

PMID- 8157272
TI  - T-cell receptor V delta gene usage by tumour reactive gamma delta T lymphocytes
      infiltrating human lung cancer.
AB  - In seven human adenocarcinomas and a non-neoplastic granulomatous disease of the
      lung, gamma delta+ infiltrating lymphocytes (TIL) could be isolated and
      selectively expanded in vitro upon culture in interleukin-2 (IL-2), without any
      additional stimuli, indicating a prior activation in vivo. In most cases gamma
      delta TIL were predominantly V delta 1+, despite a normal V delta 2:V delta 1
      ratio in paired peripheral blood lymphocytes, suggesting a possible expansion of
      this subset in response to localized antigens/superantigens. Moreover, in five
      patients it was possible to identify a V delta 1- V delta 2- TIL population which
      by polymerase chain reaction (PCR) analysis was shown to be heterogeneous as V
      delta gene usage, inclusive of V delta 3,4,5,6,7 and 8. Of note, these V delta
      regions have not been found in peripheral blood so far. Finally, in all cases,
      gamma delta TIL displayed killing activity of the autologous tumour, which
      appeared to be more restricted in the case of V delta 1+ cells. Altogether, these
      findings suggest a preferential expansion, at the tumour site, of V delta 1+
      cells and of cells expressing V delta genes other than V delta 2.

PMID- 8157273
TI  - In vitro human lymphocyte proliferative responses to a glycoprotein of the yeast
      Saccharomyces cerevisiae.
AB  - Following reports of enhanced humoral immunity to Saccharomyces cerevisiae in
      patients with Crohn's disease, and identification of an immunodominant, high
      molecular weight glycoprotein (gp200), we have investigated the cellular immune
      response to this yeast in normal individuals. Following exposure to a crude
      saline extract (Sacc), peripheral blood mononuclear cells (PBMC) from these
      subjects demonstrated dose-dependent increases in tritiated thymidine
      incorporation, the time-course of which resembled that of the response to the
      known recall antigens PPD and TT. This was accompanied by increased cytotoxicity
      of the cultured cells for natural killer (NK)-sensitive and NK-resistant target
      cell lines. Furthermore, using a purified, high molecular weight, glycoprotein
      fraction of Sacc in culture, a dose-dependent lymphoproliferative response was
      again observed. Stimulation indices (SI) for thymidine incorporation by umbilical
      cord blood lymphocytes exposed to Sacc were low compared with those of normal
      adults. These results provide evidence for possible antigen-specific, cellular,
      immune sensitization of normal individuals to a ubiquitous dietary component.

PMID- 8157274
TI  - Selective inhibition of immature CD4-CD8+ thymocyte proliferation, but not
      differentiation, by the thymus atrophy-inducing compound di-n-butyltin
      dichloride.
AB  - Effects of the thymus atrophy-inducing organotin compound di-n-butyltin
      dichloride (DBTC) on the differentiation and proliferation of immature rat
      thymocyte subsets were studied in vivo and in vitro. Incubation of freshly
      isolated CD4-CD8- or immature CD4-CD8+ (characterized as CD4-CD53-) thymocytes
      with 10(-7) M DBTC for 18 hr did not affect cell recovery or their ability to
      differentiate to CD4-CD8+ cells and CD4+CD8+ or to CD4+CD8+ cells, respectively.
      The same treatment decreased the spontaneous as well as the phytohaemagglutinin
      (PHA)-induced proliferation in both subsets. However, the inhibition of
      proliferation by DBTC of immature CD4-CD8+, but not of CD4-CD8- thymocytes,
      appeared to increase with their growth rate. Data show that differentiation of
      immature thymocytes can proceed independently of proliferation and that DBTC
      causes thymus atrophy by selectively inhibiting the proliferation of immature CD4
      CD8+ thymocytes. Administration to rats of DBTC via the diet for 14 days resulted
      in an initial decrease of thymoblast number by day 2, followed by a decrease in
      the total number of thymocytes by day 4. Total thymocyte numbers were lowest on
      day 7 and did not significantly change thereafter. CD4/CD8 thymocyte subset
      distributions were similar to controls on day 4, but on day 7 of feeding a marked
      reduction of the percentage of CD4+CD8+ thymocytes and consequently an increase
      of the percentages of the three other CD4/CD8 subsets were found. Thereafter, the
      CD4/CD8 subset distribution recovered, reaching near control values on day 14,
      despite the very low numbers of thymoblasts and of total thymocytes at that time.
      Data together indicate that DBTC reduces the production of CD4+CD8+ and mature
      single-positive thymocytes by selectively inhibiting immature CD4-CD8+ thymocyte
      proliferation but without affecting the differentiation capacity of these cells.
      This suggests that thymocyte proliferation and differentiation are separately
      regulated processes.

PMID- 8157275
TI  - Demonstration of direct xenorecognition of porcine cells by human cytotoxic T
      lymphocytes.
AB  - It is not known whether human cytotoxic T cells can recognize porcine major
      histocompatibility antigens directly, or whether recognition occurs by co
      operation with syngeneic human antigen-presenting cells (APC). Limiting dilution
      assays were used to quantify human anti-pig precursor cytotoxic T-cell (CTLp)
      frequencies and to analyse the 'kinetics' of the interaction between human
      lymphoid cells and porcine splenic cells. Single-hit kinetics are demonstrative
      of direct recognition, as only one cell type, the CTLp, is diluted out, whereas
      multi-hit kinetics indicate that more than one cell is limiting and provide
      evidence for co-operative recognition of xenoantigens. Initial assays indicated
      that the frequency of CTLp reactive with alloantigens on human splenic targets
      (mean 1/1845; n = 3) was approximately sixfold greater than the frequency of CTLp
      reactive with porcine splenic cells (1/12,082; n = 3). However, not all of the
      assays performed using the xenogeneic combination produced single-hit kinetics.
      Subsequent assays were performed by mixing limiting numbers of human peripheral
      blood mononuclear cells (PBMC) or APC-depleted PBMC preparations with porcine
      splenocytes. There was a significant difference in the frequency of xenospecific
      CTLp between PBMC and APC-depleted preparations (P = 0.034). The overall
      frequency increased in the APC-depleted group. Variation between the seven human
      donors was also significant (P = 0.006). There was no significant difference in
      frequency between the two cell preparations after correction for the proportion
      of CD3+ cells (P = 0.13). There was, however, a significant departure from single
      hit kinetics in the PBMC group (P = 0.004) which was not observed in the APC
      depleted group (P = 0.052). It is concluded that human cytotoxic T cells can be
      activated by porcine xenoantigens directly. However, the direct recognition
      mechanism can be altered in the presence of human APC.

PMID- 8157276
TI  - Transcriptional regulation by retinoic acid of interleukin-2 alpha receptors in
      human B cells.
AB  - In this study, we demonstrated that retinoic acid (RA) up-regulated interleukin-2
      receptor-alpha (IL-2R alpha) expression on two human B-cell lines, IE8.6 and
      SKW6.4. Deleted forms of the human IL-2R alpha promoter linked to the bacterial
      chloramphenicol acetyltransferase reporter gene were transfected into IE8.6 cells
      in order to define RA-responsive regulatory domains. Experiments using the -1.6
      kb construct, which contains all known regulatory regions in the IL-2R alpha
      promoter, indicated that RA could induce IL-2R alpha promoter activity. The basal
      activity of the -471 construct was initially low, but was markedly enhanced by
      the addition of RA. Deletion of promoter sequences between -471 and -317 resulted
      in a significant augmentation of basal promoter activity and abolished promoter
      induction by RA. This finding revealed a requirement for sequences 5' of base 
      317 for RA-induced promoter activation, raising the possibility of the presence
      of both a RA response element and a negative regulatory element (NRE) upstream of
      base -317. Transfection studies with internal deletion mutants with the putative
      NRE removed resulted in increases in basal promoter activity and unresponsiveness
      to RA similar to the -317 construct. In contrast, an internal deletion mutant
      with the NRE intact had low basal activity and was inducible by RA similar to the
      -471 construct. Taken together, our results suggested that RA-induced activation
      of the IL-2R alpha promoter was through changes in the function of a NRE present
      between bases -400 and -368. This 31-base pair element may interact with an
      adjacent RA-responsive regulatory site as well as being responsible for down
      regulation of basal IL-2R alpha expression under certain conditions.

PMID- 8157277
TI  - Enhanced protection against respiratory influenza A infection in mice by liposome
      encapsulated antibody.
AB  - Liposome-mediated passive immunity was evaluated for its efficacy in the
      prophylaxis and treatment of influenza A/PR/8 virus infection in mice. A mouse
      LD50 protection model was developed using a polyclonal anti-influenza A antibody
      which demonstrated strong reactivity against the mouse-adapted virus in a
      fluorogenic enzyme immunoassay and in an in vitro plaque assay. Using liposomes
      as an antibody carrier system, the delivery of antibody to the lungs was
      optimized. For mice given the antiviral antibody intranasally 24 h prior to
      challenge with 10 LD50 of mouse-adapted influenza A/PR/8 virus, the survival rate
      at 14 days post-challenge was 60%. However, when mice were given antibody
      encapsulated within liposomes, the survival rate increased to 100%. In the
      treatment of mice preinfected with 10 LD50 of the virus, mice were fully
      protected (100% survival rate) when treated within 8 hr post-infection with free
      unencapsulated antibody, or within 12 hr with liposome-encapsulated antibody. It
      is postulated that the improved therapeutic and prophylactic efficacies of the
      antiviral antibody may be attributed to enhanced delivery as well as retention of
      antibody molecules in the lungs when liposomes are used as antibody carrier
      system.

PMID- 8157278
TI  - Characterization of a novel monoclonal antibody against human perforin using
      transfected cell lines.
AB  - The role of perforin in cytotoxicity is controversial. This paper characterizes a
      novel monoclonal antibody (anti-Phu) against human perforin, using murine cell
      lines transfected with human perforin cDNA. The antibody specifically stains
      human perforin in transfected mouse CTLL-2. Anti-Phu blocked granule-mediated
      haemolysis in an in vitro assay using intact granules isolated from the natural
      killer (NK)-like human cell line YT, indicating that perforin is a major granule
      component causing lysis of red blood cells (RBC) in this assay. Inhibition of
      haemolysis by anti-Phu demonstrated that the antibody binds to undenatured
      protein as well as fixed perforin molecules. However, the antibody did not
      inhibit lysis by an allospecific T-cell clone or by YT cells. This could be due
      to an extremely tight contact between effector and target cell, preventing the
      antibody from interfering with perforin function by steric hindrance.
      Physiologically this may reduce lysis of bystander cells. The anti-Phu antibody
      is a useful tool for further studies of perforin-induced cytotoxicity in vitro
      and in vivo.

PMID- 8157279
TI  - Role of N-terminal domain of histidine-rich glycoprotein in modulation of
      macrophage Fc gamma receptor-mediated phagocytosis.
AB  - A brief exposure of murine peritoneal inflammatory macrophages to plasma
      histidine-rich glycoprotein (HRG; 77,000-81,000 MW) for 1-2 hr increased Fc gamma
      receptor (Fc gamma R) expression and phagocytic function in these cells. However,
      a continual culture of the cells without the presence of HRG for the next 18-48
      hr resulted in down-regulation of Fc gamma R expression and phagocytic function.
      Similarly, HRG decreased Fc gamma RII expression in less differentiated human THP
      1 monocytic cells during treatment for 18 hr, as determined by cellular ELISA and
      metabolic labelling. The molecular mechanism by which HRG regulates Fc gamma R
      expression is unknown. However, at a relatively high concentration (> 1
      microgram/ml), HRG altered the cellular metabolism by increasing cellular protein
      synthesis but reducing protein secretion. These observations suggest a likely
      mechanism for the HRG-mediated reduction of Fc gamma R expression. A degraded HRG
      (40,000 MW) which possessed an identical N-terminal sequence as that of the
      native HRG was capable of decreasing macrophage Fc gamma R expression and
      phagocytosis. The results indicate that the functional domain of HRG responsible
      for binding to macrophages is localized to the N-terminal half.

PMID- 8157280
TI  - A high iodine intake in Wistar rats results in the development of a thyroid
      associated ectopic thymic tissue and is accompanied by a low thyroid autoimmune
      reactivity.
AB  - Evidence is accumulating that dietary iodine intake is an important modulator of
      autoimmune thyroid reactions. To study this role of iodine intake further, female
      Wistar rats were kept on an enriched iodine diet (EID, iodine intake 100
      micrograms iodine/day) for a period of up to 18 weeks. Control rats were either
      on a normal iodine diet (NID, iodine intake 7 micrograms iodine/day) or a low
      iodine diet (LID, 2 days of 1% KClO4 followed by iodine-deficient drinking
      water/pellets). During the first 6 weeks of the EID rats developed a thyroid
      associated ectopic thymic tissue (50-57% of the animals on EID versus 7-14% of
      NID rats and 0% of LID rats). This thyroid-associated ectopic thymic tissue
      showed a similar histology (cortex and medulla) and a similar marker pattern as
      normal rat thymus concerning TdT expression (positive cells in the cortex) and
      CD4/CD8 positivity (double-positive cells in the cortex, single-positive cells in
      the medulla). The excessive iodine diet also resulted in a lowered thyroid
      autoimmune reactivity as compared to the NID and LID, viz. (1) in a lower
      incidence of anti-colloid antibodies in serum (12.5% positivity in EID rats
      versus 36% in NID and 60% in LID rats at 18 weeks) and (2) lower numbers of
      intrathyroidal lymphoid cells, viz. lower numbers of dendritic cells and lower
      numbers of CD4 and CD8 positive lymphocytes. It is hypothesized that the
      development of the thyroid-associated ectopic thymic tissue in the EID rats is
      related to their low thyroid autoimmune responsiveness; the tissue might play a
      role in tolerance induction to thyroidal autoantigens.

PMID- 8157281
TI  - Reduction of spontaneous autoimmune diabetes in diabetes-prone BB rats with the
      novel immunosuppressant fusidic acid. Effect on T-cell proliferation and
      production of interferon-gamma.
AB  - Diabetes-prone (DP) BB rats spontaneously develop a hyperglycaemic condition
      which closely resembles human insulin-dependent diabetes mellitus (IDDM), both in
      terms of clinical and histological features. The incidence of IDDM was
      significantly reduced when these animals were treated with 2 or 4 mg fusidic acid
      (FA)/day i.m. from day 30 to day 120 of age. In addition, the mean insulitis
      score was significantly diminished in the animals treated with FA compared to
      both vehicle-treated and untreated controls. Finally, 2 mg/day of FA i.m.
      prevented cell proliferation and interferon-gamma secretion from peripheral blood
      mononuclear cells upon ex vivo stimulation with concanavalin A. The capacity of
      FA to substantially reduce the incidence of autoimmune diabetes in a well-known
      animal model of human IDDM supports previous observations regarding the
      immunosuppressive properties of FA and its potential use in the treatment of
      human autoimmune diabetes.

PMID- 8157282
TI  - Inhibition by anti-sperm monoclonal antibodies of the penetration of zona-free
      hamster oocytes by human spermatozoa.
AB  - Fourteen mAb specific for human sperm membrane antigens were selected to
      investigate their inhibitory effect on fertilization. The antigens were not
      expressed in other human somatic tissues but were present in sperm from other
      species. The antibodies were purified from ascites fluid produced in mice. The
      zona-free hamster egg penetration assay was used for the evaluation of the
      blocking ability of these antibodies. The inhibition rate was generally related
      to a decrease in the number of adherent sperm. Three groups of antibodies were
      distinguished: (i) four mAb that have high inhibition at any concentration; (ii)
      four mAb with an intermediate inhibitory effect, that is more dependent on the
      antibody concentration tested; and (iii) six mAb with little or no effect at any
      concentration. The presence of antibodies leads to a lower penetration index, or
      number of penetrating sperm per oocyte. MAb specific for head antigens promote
      high inhibition of fertilization; these antibodies show a patchy staining on the
      sperm head. The antibodies localized in the midpiece have an intermediate
      inhibitory effect. No inhibition is detected with the equatorial region binding
      pattern. Sperm agglutination does not play any role in the inhibition caused by
      the antibodies described here.

PMID- 8157283
TI  - Characterization of a novel leucocyte activation antigen recognized by the
      antibody CMRF-37.
AB  - We describe a novel activation antigen recognized by the monoclonal antibody CMRF
      37, which is absent or only weakly expressed on resting cells but is rapidly
      induced on T cells, B cells and monocytes following stimulation. Its kinetics of
      expression (12-24 h after the addition of the inductive signal) indicate that it
      is an early activation antigen. The cellular distribution and expression kinetics
      of the CMRF-37 antigen differ from other known activation antigens and as such
      should be a useful marker of human leucocyte activation.

PMID- 8157284
TI  - A 3.5 kb deletion in the glycophorin C gene accounts for the Gerbich-negative
      blood group in Melanesians.
AB  - The Gerbich-negative blood group types are rare in most populations, but reach
      appreciable frequencies in certain Melanesian groups in Papua New Guinea. The
      recent cloning of the human glycophorin C (GPC) gene, that encodes Gerbich (Ge)
      blood group antigens, has facilitated study of its genetic variants. We have
      obtained partial genomic clones of a normal GPC gene, for molecular analysis of
      Ge: -1, -2, -3 types in Melanesians, and have shown that a 3.5 kb deletion in the
      GPC gene that removes all of exon 3 accounts for at least one Gerbich-negative
      phenotype in Melanesians. Population distributions of GPC RFLP have shown that
      the deletion-type GPC is not confined to mainland Papua New Guinea as previously
      thought, but occurs sporadically in Melanesians from Fiji as well as in
      Micronesians.

PMID- 8157285
TI  - Differences in epitopes recognized by T cells during oral tolerance and priming.
AB  - Feeding protein antigens to mice normally leads to the development of oral
      tolerance but under some circumstances, feeding can lead to immunity, for
      example, following pretreatment of mice with cyclophosphamide (CY). In both
      cases, however, it is possible to detect sensitized T cells in the spleen and
      mesenteric lymph nodes (MLN) by in vitro lymphokine release for granulocyte
      macrophage-CSF (GM-CSF) and IFN-gamma. This study examines the recognition of the
      immunodominant T cell epitope on ovalbumin (OVA) following intragastric priming
      and tolerance. T cells from CY/OVA treated mice and cells from mice injected
      subcutaneously with OVA in CFA responded well to both OVA and the H2d restricted
      peptide epitope pOVA323-339 releasing GM-CSF. On the other hand MLN or spleen T
      cells from tolerized mice which responded to the protein in vitro did not
      recognize the immunodominant determinant. The cells responding from tolerized
      mice were restricted by the class II MHC so these results show there can be
      differential recognition of T cell epitopes between oral priming and tolerance.

PMID- 8157286
TI  - A flow cytometric study of cell death: failure of some models to correlate with
      morphological assessment.
AB  - The balance between cell death and cell proliferation is a significant factor in
      the growth kinetics of normal and neoplastic tissues. Distinction between the two
      major forms of cell death, necrosis and apoptosis, is now recognized as important
      in understanding mechanisms regulating cell survival. A recent approach in the
      study of apoptosis has been the use of flow cytometry, with some reports
      indicating that, when stained with propidium iodide (PI), the DNA of apoptotic
      cells has decreased fluorescence compared with that of viable cells. In this
      study, we investigated a flow cytometric procedure which used the simultaneous
      analysis of DNA content and 90 degrees light scatter (90LS). Significant
      differences in the PI staining pattern and a shift in 90LS were observed when
      apoptotic death occurred at different stages of the cell cycle. Importantly, such
      differences only allowed accurate quantification of apoptosis when it occurred in
      G1. While necrosis could be distinguished from apoptosis when examined during its
      early stages, a similar staining pattern to that found with apoptosis was
      observed when necrosis was examined during its latter stages. The results
      indicate that the measurement of DNA staining cannot be exclusively relied upon
      to detect apoptosis occurring in all models. However it is useful in the
      investigation of this process when the death occurs in G1, in that the method
      offers a rapid means for quantification.

PMID- 8157287
TI  - Metabolic consequences of methotrexate therapy in tumour-bearing rats.
AB  - The metabolic response of the tumour-bearing host to methotrexate (MTX) therapy
      was investigated with particular attention to effects resulting from MTX-induced
      anorexia. Biochemical changes in female Dark Agouti rats bearing mammary
      adenocarcinomas and treated with MTX (0.5 mg/kg, 2 i.m. injections, 24 h apart)
      were compared with untreated (CON) tumour-bearing rats, and tumour-bearing rats
      pair-fed (PF) to the MTX group. MTX treatment halted progression of the tumour
      (tumour 6% of bodyweight) while the tumour burden doubled in the CON and PF
      groups. A number of biochemical and haematological changes were specific to MTX
      treatment and did not result from decreased food intake. MTX treatment was
      associated with significantly decreased plasma calcium, bilirubin, alkaline
      phosphatase, aspartate aminotransferase and the total white cell count. Decreases
      in plasma albumin and total protein concentrations were observed in both MTX and
      PF rats. Other parameters commonly used to assess renal and liver function were
      not significantly affected by MTX. MTX reversed the hypoglycaemia,
      hyperketonaemia and hypertriglyceridaemia induced by tumour-bearing. In contrast,
      PF rats had an even more pronounced hypoglycaemia and hyperketonaemia than the
      CON rats. Measurement of glucose uptake in vivo with 2-deoxy[U-14C]-glucose
      showed that MTX treatment halved the glucose requirement of the tumour (8.2% of
      bodyweight compared to 12.2% in the control). It is concluded that the
      potentially adverse effects of MTX treatment on host metabolism are outweighed by
      the beneficial effects of a reduced metabolic demand resulting from inhibition of
      tumour progression.

PMID- 8157288
TI  - Stimulation of gastrointestinal antibody to Shiga toxin by orogastric
      immunization in mice.
AB  - Shiga toxin (ST) is a protein toxin of Shigella dysenteriae type 1, a causative
      agent of severe diarrhoea and dysentery. In this report we describe the
      gastrointestinal secretory antibody response of mice following orogastric
      immunization with ST. Gastrointestinal secretions were sampled by a
      gastrointestinal lavage technique weekly for 5 weeks after initial immunization.
      Assay of lavage samples by ELISA showed that mice vaccinated orogastrically with
      various doses of ST developed gastrointestinal antibody to ST in a dose-dependent
      manner. Serum anti-ST activity developed by 5 weeks after initial immunization.
      The ability of ST to act as a mucosal immune adjuvant was investigated by
      coadministration of ST and keyhole limpet haemocyanin. In contrast to cholera
      toxin, a potent adjuvant, ST did not demonstrate adjuvant activity. The mouse
      gastrointestinal lavage model could be useful for further analysis of the
      cellular basis of ST immunogenicity.

PMID- 8157289
TI  - Persistence of gamma/delta T cell oligoclonality in the peripheral blood of
      rheumatoid arthritis patients.
AB  - The peripheral blood of patients with rheumatoid arthritis (RA) contains
      oligoclonal gamma/delta T cell populations which may contribute to the
      pathogenesis of the disease. To investigate whether there is persistent
      gamma/delta T cell oligoclonality in RA peripheral blood, we screened polymerase
      chain reaction-amplified T cell receptor (TCR) cDNA, derived from peripheral
      blood mononuclear cells (PBMC) of four RA patients, with sequence specific
      oligonucleotides (SSO). The SSO used were specific for TCR variable (V) delta 1,
      V delta 2 and V gamma 9 transcripts comprising V-joining (J) junctions found over
      represented in PBMC of the same RA patients, when bled up to 3 years previously.
      The dominant transcripts were expressed in the new PBMC samples, although in most
      cases at a lower frequency than was originally detected. In one patient there was
      almost 100% oligoclonality of V gamma 9-(N)-J gamma 2 junctional region sequences
      among the V gamma 9 cDNA clones, progressing from 55% oligoclonality in 15
      months. These results indicate the persistence of clonally expanded gamma/delta T
      cells in the peripheral blood of RA patients. Whether this reflects continual
      endogenous or exogenous antigenic stimulation remains to be investigated. The
      findings presented in this report may have important therapeutic implications in
      view of the potential for immuno-intervention for the treatment of human
      autoimmune disorders, like RA.

PMID- 8157290
TI  - Molecular associations involving CD16, CD45 and zeta and gamma chains on human
      natural killer cells.
AB  - zeta (CD3-zeta) and gamma (Fc epsilon RI gamma) chains associate with CD16, the
      low affinity receptor for IgG (Fc gamma RIII) on human NK cells and are essential
      for the cell surface expression of CD16 and for CD16-mediated effector functions.
      This study has investigated whether, on NK cells, molecules other than CD16
      associate with zeta and gamma chains, as a method of identifying other NK cell
      surface molecules important in NK cell function. Cell surface biotinylated NK
      cells were lysed in digitonin, and the lysates immunoprecipitated with mAb to
      CD16, zeta and gamma, and the immunoprecipitates analysed by SDS-PAGE. CD16 mAb
      co-precipitated zeta and gamma chains (16 and 12kD, respectively) and in addition
      molecules of 24, 32-35, 100, 150 and 180-200 kD. Also, zeta mAb co-precipitated
      gamma chain, and molecules of 24-26, 32-35, 48, 50-66, 100, 150 and 180-200 kD;
      and gamma co-precipitated zeta chain, and molecules of 24-26, 29, 32-35, 37, 45,
      49, 50-66 and 100 kD. While significant amounts of zeta and gamma were co
      precipitated with CD16, 10 to 12-fold more zeta and gamma were immunoprecipitated
      with their respective mAb. Furthermore, depletion of CD16 from the lysate
      resulted in only a partial (10-12%) depletion of zeta and gamma, indicating that
      only a relatively small proportion (10-12%) of these molecules are associated
      with CD16. Interestingly, substantial amounts of molecules with electrophoretic
      mobility similar to CD16 (50-66 kD) were co-precipitated with zeta and gamma
      chain mAb from lysates depleted of CD16. In contrast to NK cells where zeta
      associated with a number of different molecules, the majority of zeta in T cells
      was found to be associated only with the TCR:CD3 complex. NK cells showed a
      strong association between CD45, CD16 and a 33 kD molecule and often a strong
      association of zeta with CD16, CD45 and an unidentified molecule of approximately
      150 kD. Our results show first, that CD16, zeta and gamma each can be efficiently
      labelled by cell surface biotinylation, and second, that CD16, zeta and gamma
      each can form a complex with each other, and with a number of additional
      molecules including a 33 kD molecule and CD45 potentially important in NK cell
      function.

PMID- 8157291
TI  - The enigma of cytokine redundancy.
AB  - The redundancy of many cytokine functions that was first noted in vitro has now
      been confirmed in vivo with the demonstration that some of these functions can
      occur in mice rendered deficient in a cytokine or cytokine receptor by gene
      inactivation. Other functions are ablated in these mice, suggesting that they are
      cytokine-specific. Although some of the underlying mechanisms have been
      identified, it remains unclear why certain activities of a cytokine should be
      unique and others redundant. It is proposed that compensatory mechanisms exist
      only for those cytokine functions whose inappropriate or excessive activation
      would not be pathogenic or whose importance justifies this risk. Conversely,
      cytokine-specific functions might be those that should be tightly regulated to
      avoid the pathological consequences of their inadvertent expression.

PMID- 8157292
TI  - Serum inorganic phosphate levels in experimental intestinal ischaemia.
AB  - Serial serum inorganic phosphate estimates were done following production of
      experimental intestinal ischaemia in dogs by occlusion of superior mesenteric
      artery (10 dogs) or vein (10 dogs) and compared to phosphate values in control
      dogs (5 for each experimental group). Elevated phosphate values were seen within
      one hour after ischaemia. Elevation was more marked following arterial occlusion,
      becoming statistically significant within 2 hours. It is suggested that serum
      inorganic phosphate elevation can be used as important laboratory test in early
      diagnosis of acute intestinal ischaemia.

PMID- 8157293
TI  - Examination stress in medical student: a study.
AB  - The present study was conducted on 40 male and 10 female students appearing for
      the 1st MBBS examination. Two readings of pulse rate, blood pressure and electro
      cardiogram were taken viz 6 months (control) and 10 minutes prior to the
      examination. A significant increase was seen in the pulse rate and blood pressure
      readings before the examination as compared to the control readings. However, no
      significant change was observed in electro cardiographic recordings.

PMID- 8157294
TI  - Chemotherapy and combination therapy in anaplastic thyroid carcinoma.
AB  - The majority of patients with anaplastic thyroid carcinoma will achieve local
      tumour control with a combination of pre- and postoperative chemotherapy and
      radiotherapy. A few patients may even be cured with this regime. Chemotherapy
      alone for advanced thyroid carcinoma cannot, however, be routinely recommended.
      The chemotherapeutic agents in current use are discussed. Multimodality treatment
      remains the treatment of choice for undifferentiated thyroid carcinoma.

PMID- 8157295
TI  - Frusemide--digitalis interaction on experimental model.
AB  - Interaction of frusemide and digitalis on frog heart has been studied. It was
      found that like digitalis, frusemide did not have any effect on normal heart, but
      restored the normal myocardial contraction of the hypodynamic frog heart.
      Frusemide induced cardiac arrest when administered during digoxin infusion. It is
      suggested that interaction of frusemide and digoxin has additive effect.

PMID- 8157296
TI  - "Parthenium dermatitis: an unsuspected allergy".
AB  - Congress grass (Parthenium hysterophorus) is a common weed growing wild in the
      urban and semiurban environs of North India. Cases of eczematous dermatitis
      caused by it generally escape clinical detection and are consequently wrongly
      diagnosed. An interesting case of Parthenium dermatitis treated with a high-dose
      course of desensitisation is presented to underscore the probability of the
      entity in obscure cases of contact dermatitis and eczema.

PMID- 8157297
TI  - Specific problems of health in elderly.

PMID- 8157298
TI  - Tuberculosis: an epidemic in the making.

PMID- 8157299
TI  - Correlation between the isolation of Mycobacterium tuberculosis and estimation of
      mycobacterial antigen in cisternal, ventricular and lumbar cerebrospinal fluids
      of patients with tuberculous meningitis.
AB  - In the study Mycobacterium tuberculosis was isolated in the cerebrospinal fluid
      (CSF) specimens of patients with tuberculous meningitis (TBM) by the conventional
      bacteriological technique. The isolation rate of M. tuberculosis was found to be
      11.5% in lumbar, 75% in ventricular and 87.5% in cisternal CSFs. Low isolation
      rate of M. tuberculosis in lumbar CSF is due the low density of tubercle bacilli
      in lumbar CSF than in cisternal CSF. However M. tuberculosis antigen 5 is present
      in significant concentration in CSFs. The antigen concentration in CSF was
      estimated by an inhibition enzyme-linked immunosorbent assay (ELISA). Since CSF
      specimens can not be collected from ventricular or cisternal routes for the
      routine bacteriological investigations in patients with TBM, estimation of M.
      tuberculosis antigen 5 concentration in lumbar CSF by an inhibition ELISA may be
      considered as an adjunct in the laboratory diagnosis of TBM. This is particularly
      relevant in those patients in whom bacteriological methods fail to demonstrate M.
      tuberculosis in CSF specimens.

PMID- 8157300
TI  - Enzyme-linked immunosorbent-assay for antigen detection in tuberculous
      meningitis.
AB  - Two systems of Competitive Enzyme linked immunosorbent assay (ELISA) were
      developed to detect Mycobacterial antigen in cerebrospinal fluid (CSF) for the
      diagnosis of tuberculous meningitis (TBM)--one by using indigenously prepared
      Anti-M.tuberculosis H37Rv-Penicillinase conjugate (Method I) and another by using
      commercially available Anti M. bovis BCG-Horse Radish Peroxidase (HRP) conjugate-
      (Method II). The tests were used to analyse CSF of 148 patients clinically
      confirmed as having TBM and 278 control subjects. By using > or = 10 ng/ml as the
      cut-off value for Method I and > or = 1 ng/ml as that for Method II, the
      specificity for both were 100% and positivity was 79.73% and 67.57% respectively.
      A follow up study in 26 TBM cases after 2 weeks (16 cases), 4 weeks (13 cases)
      and 4-12 months (10 cases) of antituberculous treatment revealed that
      mycobacterial antigen persisted in the majority of cases even after 4 weeks of
      the treatment.

PMID- 8157301
TI  - Serodiagnosis of extrapulmonary tuberculosis by ELISA.
AB  - This study aims at evaluating the specificity and sensitivity of ELISA test in
      detection of Mycobacterial Antibodies using A60 antigen. Sera from 100 clinically
      suspected cases of extrapulmonary tuberculosis were studied along with 10 sputum
      positive cases 25 age and sex matched healthy control. Overall positivity of the
      test was 80.00 per cent with 100 percent sensitivity and 92 per cent specificity.
      The present study recommends ELISA as an adjunct to other investigative
      procedures.

PMID- 8157302
TI  - Tuberculous endometritis in hills of Darjeeling: a clinicopathological and
      bacteriological study.
AB  - Combined histological and bacteriological investigations of 800 specimens of
      nonpregnant endometrial curettings of 15 to 60 years age group of hill women of
      Darjeeling District were carried out for detection of tuberculous endometritis.
      The principal complaints were infertility (47.5 per cent), abnormal uterine
      bleeding (30.75 per cent), amenorrhoea (11.25 per cent), leucorrhoea (6.25 per
      cent), and miscellaneous conditions (pelvic pain and pyometra) (4.25 per cent)
      cases. By histological examination alone, only 10.9 per cent cases could be
      diagnosed while by combined study the incidence rate was 11.8 percent, an
      increase in the diagnostic acumen by more than 10.3 per cent. Bacteriological
      study was of greater value in doubtful cases where there was absence of
      tuberculous granuloma or epithelioid cell but presence of nonspecific
      inflammatory cells along with variable degree of necrosis of glandular epithelia.
      The incidence of M.tuberculosis was 97.7 percent while that of atypical
      mycobacteria was 2.3 per cent. Thus simultaneous use of culture and biopsy
      yielded better results. Our prevalence is a little higher than other reports from
      India. In cold weather at a high altitude, the tubercle bacilli survive longer in
      fomites which serve as important sources of infection in Darjeeling. Women of
      third decade are more frequently affected (43.2 per cent).

PMID- 8157303
TI  - A new medium for rapid slide culture of tubercle bacilli.
AB  - Human blood medium (HBM) and egg enriched sheep blood medium (SBM) were evaluated
      to see their efficacy for primary culture of tubercle bacilli. SBM is found to be
      equally effective compared to HBM. Both types of media were associated with a low
      rate of contamination (2.75%). Availability of culture results after 7 days
      compared to 6 weeks on Lowenstein-Jensen media is a distinct advantage of slide
      culture method with a possible use in primary isolation and in evaluation of drug
      sensitivity pattern of Mycobacterium tuberculosis.

PMID- 8157304
TI  - Effect of hemoglobin on the growth of mycobacteria and the production of
      siderophores.
AB  - Hemoglobin is known to support the growth of several bacterial species. The
      growth and the production of siderophores by 4 strains of mycobacteria in the
      presence of hemoglobin was studied in vitro. The findings were compared with
      those obtained in the presence of equivalent concentrations of iron in the
      medium. Increase in the concentrations of hemoglobin caused an appreciable
      increase in the growth of all 4 strains. This was however, accompanied by a
      significant decrease in the production of both exochelins and mycobactins. It was
      also observed that hemoglobin supported the growth of all strains as well as that
      with free iron and the concentrations of both siderophores was significantly
      higher in the presence of hemoglobin than in that of free iron.

PMID- 8157305
TI  - HIV-1 seropositivity in pulmonary tuberculosis (study of 340 cases from
      Marathwada).
AB  - An investigative study was carried out in 340 cases of established pulmonary and
      presumed pleural tuberculosis for co-occurrence of HIV-1 infection in them.
      Confirmatory screening for HIV-1 was carried out with both ELISA (Vironostika)
      and Serodia commercial kits in all reactive samples on first screening. In all,
      16 cases proved to be having HIV-1 coexistent infection with pulmonary
      tuberculosis. Their preliminary vital clinical observations and roentogenic
      finding are summarized and literature reviewed briefly.

PMID- 8157306
TI  - Female genital tuberculosis--a retrospective clinico-pathologic study of 501
      cases.
AB  - A retrospective clinico-pathological study of 501 cases of female genital
      tuberculosis (FGTB) observed from 1974 to 1991 was conducted. The frequency of
      FGTB was 1.8% in 1974 rising to 2.4% in 1982, thereafter showing a steady decline
      to 0.8% in 1989 and onwards. Two thirds of the patients were infertile and
      between 17 to 40 years of age, while 82.3% of all cases of FGTB were between 20
      30 years of age. Involvement of the endometrium was noted in 99.5%, fallopian
      tubes in 94.7%, cervix in 81.5%, ovaries in 62.5% and vulva in 0.2% of cases.
      Extensive caseous lesions in the genital tract were a notable feature in elderly
      women 70 years of age. Staining for Acid Fast Bacilli was not found to be useful,
      however follow-up biopsies from endometrium and cervix in 45 cases on anti
      tubercular therapy showed complete disappearance of the granulomas.

PMID- 8157307
TI  - Cerebro-spinal fluid cytomorphology in tuberculous meningitis--a preliminary
      report.
AB  - The morphology of cells in centrifuged cerebrospinal fluid (C.S.F.) of 25
      patients with tuberculous meningitis (T.B.M.) in different stages of the illness
      is presented. Blood brain barrier studies were also done in 6 patients. Maximum
      variability of cells in the initial stages of the illness and persistence of
      polymorphs in the later stages of the illness is noted. No correlation was
      established between cerebrospinal fluid cytomorphology and complications of the
      illness.

PMID- 8157308
TI  - A cholera-coli related enterotoxin production by different Shigella species.
AB  - A cholera-coli related enterotoxin production was studied in 50 different
      Shigella isolates from cases of childhood diarrhoea. Four out of 6 Sh.
      dysenteriae, 18/37 Sh. flexneri and 2/4 Sh. sonnei were found to be enterotoxin
      producers by RIL test. All strong RIL positive strains were isolated from cases
      of severe diarrhoea, indicating the association of enterotoxin production and
      severity of acute diarrhoea. Two major protein bands were observed in SDS-PAGE
      and W.B. EIA assay in all positive RIL extracts. These immuno-reactive bands were
      at 31 kDa and 14 kDa positions resembling A-B subunit structure of cholera-coli
      family of enterotoxins.

PMID- 8157309
TI  - Primary carcinoma of the ureter--a 24-year-study from south India.
AB  - This study from India has envisaged a characterization of primary carcinomas of
      the ureter using a review of all available Indian literature over a period of 32
      years. The character of the tumor in the Indian patients was clinically; pain,
      abdominal lump and haematuria with most neoplasms being single, situated in the
      ureteric pelvis and such neoplasms being squamous cell in type. The others were
      transitional cell carcinomas. Similar ureteric neoplasms reported from Western
      literature showed that the reporting authors gave the predominant complaint as
      haematuria alone, the neoplasm being usually multicentric and histologically
      mainly transitional cell carcinoma. Although a significant follow up could not be
      achieved among the 101 Indian patients, Western authors found that muscle
      invasion was the single most important histologically related point to endanger a
      good progress. The possible pathogenesis that could be thought of appears to be
      related to stasis.

PMID- 8157310
TI  - Sweat osmolality in some of the congenital diseases.
AB  - Sweat osmolality pattern was studied in Indian sub population of both controls
      and patients with congenital diseases. A Normal range for sweat osmolality was
      established for different age groups and sex (100-150 mmols/kg) and compared with
      the patients, who were clinically diagnosed as cystic fibrosis, Down's syndrome
      and mentally retarded cases. The study has revealed that sweat osmolality varies
      according to age and sex in normal population implying the effect of
      endocrinological changes associated with the onset of puberty. Further, it was
      also observed that an elevated sweat osmolality is not unique to cystic fibrosis
      alone, but seen among the Down's syndrome and some of the mentally retarded cases
      where in the etiology is traced to the inborn errors of metabolism.

PMID- 8157311
TI  - Enteropathogenic bacteria in river Ganges in Varanasi.
AB  - A bacteriological study of the river Ganges in Varanasi was carried out from
      December 1985 to November 1987. In all 407 water samples were collected, 335 from
      bathing ghats and 72 from sewage openings and were examined for the presence of
      enteropathogenic bacteria. Vibrio cholerae 0-1 (1.72%), Non 0-1 Vibrio cholera
      (3.69%), Vibrio fluvialis (0.74%), Aeromonas sp. (0.49%), Plesiomonas sp.
      (0.25%), Salmonella sp. (0.98%) and Shigella sp. (1.23%) were isolated from both
      ghats and sewage openings along with Pseudomonas sp., Proteus sp., E. coli., etc.
      This indicates that water of the river Ganges is potentially hazardous to the
      health of the bathers and is not suitable for drinking. The discharge of raw
      sewage into the river and its diversion beyond the city, downstream, by
      installation of pumps have failed to improve the quality of water.

PMID- 8157312
TI  - A simple device for performing fine needle aspiration cytology.
AB  - A Simple reusable device has been fabricated from the barrel of the ten ml
      plastic disposable syringe to hold the piston of 20 ml disposable syringe for
      Fine Needle Aspiration Cytology (FNAC), in position of full retraction so as to
      produce continuous negative pressure inside. The device has been found very
      satisfactory inexpensive and has special relevance to situations where the
      standard syringe holder is not available.

PMID- 8157313
TI  - Fine needle aspiration biopsy cytology of chondrosarcoma.
AB  - The cytomorphological appearances of bone and soft tissue tumours, when combined
      with radiology and clinical presentation, can lead to a positive diagnosis in the
      majority of cases. Our experience with fine needle aspiration biopsy of 13 cases
      of chondrosarcoma, encountered over a four year period is presented, in
      correlation with their radiological appearances. It is concluded that. FNAB is a
      valuable pre-operative tool in characterising chondroid neoplasms in soft tissue
      and bone.

PMID- 8157314
TI  - Accuracy of fine needle aspiration cytology of abdominal masses without
      radiological guidance.
AB  - This study was undertaken to evaluate the accuracy of FNAC of abdominal masses
      without the help of radiological guidance and to determine factors which affect
      the outcome of the procedure. Five hundred consecutive patients were studied.
      FNAC was reported by a single cytopathologist without knowledge of subsequent
      histology. In calculating indices of accuracy of FNAC only those patients in whom
      both FNAC and histology reports were available (N = 383) were considered. The
      overall incidence of unsatisfactory specimens was 5.6%. Consistency of the mass
      did not affect accuracy of FNAC. However, age (below 12 years) plane of the
      swelling, mobility of mass and size of the swelling, all significantly affected
      the adequacy of cytological yield. The overall true positive rate was 100.0% and
      there were no false positives. The true negative rate was 40.2% and false
      negative rate was 70.9%. The high false negative rates in hepatic and pancreatic
      lesions can be reduced by imaging techniques. Luminal organs had poor accuracy
      rates. The overall accuracy rate was 73.5%, comparable to that reported in
      literature. A positive diagnosis of malignancy had a 100% predictive value.
      Overall, it appears that nonguided FNAC is as accurate as guided FNAC except for
      very small lesions or discrete lesions such as hepatic secondaries where guidance
      may be useful.

PMID- 8157316
TI  - Comparative study in cattle and buffaloes for evaluation of various diagnostic
      tests for brucellosis.
AB  - Serum samples from 1134 vaccinated and non vaccinated animals (775 cattle and 359
      buffaloes) were screened with different serological tests like Rose Bengal plate
      Test (RBPT), plate agglutination test (PAT) and standard tube agglutination test
      (SAT). The agreement between these three screening tests was 87.19% and 97.86% in
      vaccinated and non vaccinated cattle while corresponding figures in buffaloes
      were 91.56% and 84.42%. Among vaccinated animals a positive percentage of 12.8
      and 8.8 was noticed in cattle was 4.7 and 6.3, respectively by RBPT. All the
      positive sera samples were further tested by mercaptoethanol test (MET) and heat
      inactivation test (HIT) to conform the result of screening tests and to
      differentiate vaccinal titre from that of active infection. It was concluded that
      RBPT is overall best screening test to diagnose bovine brucellosis. MET and HIT
      are good supplementary tests but MET is better than HIT both in cattle and
      buffaloes. Some high titered non vaccinated buffaloes were negative in RBPT but
      positive by all other tests.

PMID- 8157315
TI  - A simple screening procedure for detection of infraclinical cases of multiple
      myeloma.
AB  - Agarose Gel Serum Electrophoresis is a simple, rapid and sensitive technique
      routinely used for diagnosis of Multiple Myeloma. Its effectiveness as a
      screening tool for detecting infraclinical cases of Multiple Myeloma is brought
      out in this study. 29 out of the 219 patients presenting with unexplained
      osteoporosis and pain are found to be positive for M proteins. These patients
      were earlier adjudged organic disease free after preliminary investigation and
      examination.

PMID- 8157317
TI  - Sporotrichosis of abdominal wall.
AB  - A rare case of sporotrichosis of abdominal wall has been described from high
      mountainous region of Himachal Pradesh. Its clinical importance has been
      discussed in the light of available literature.

PMID- 8157318
TI  - Case reports of chromomycosis.
AB  - Two cases of chromomycosis were diagnosed in B.Y.L. Nair Charitable Hospital
      during the years 1980-1989. Isolates were identified as Fonsecea compactum.

PMID- 8157320
TI  - Primary Ewing's sarcoma of the base of skull: a case report.
AB  - Primary cranial Ewing's sarcoma is an exceptionally rare lesion and only eleven
      cases have so far been reported. In this report we describe a case of primary
      Ewing's sarcoma arising from the floor of middle cranial fossa. Salient clinical,
      neuroradiological and light microscopic features in this case are described. A
      brief review of earlier published cases of primary cranial Ewing's sarcoma are
      also presented.

PMID- 8157319
TI  - Congenital adenomatoid malformation of lung: a case report.

PMID- 8157321
TI  - Angiomyolipoma of kidney: a case report.
AB  - Renal angiomyolipomas are relatively uncommon renal tumors which grossly resemble
      renal cell carcinoma. In view of the paucity of renal angiomyolipoma in the
      Indian literature, we are reporting one case in a 28 year old female without
      tuberous sclerosis.

PMID- 8157322
TI  - Harlequin foetus.

PMID- 8157323
TI  - Red grain mycetoma caused by Actinomadura pelletieri in western Rajasthan: report
      of two cases.

PMID- 8157324
TI  - Diagnosis of pulmonary strongyloidiasis by sputum cytology: a case report.

PMID- 8157325
TI  - Carcinosarcoma of parotid gland having osteosarcoma as sarcomatous component: a
      case report.
AB  - We report a rare case of carcinosarcoma of parotid gland in a pleomorphic
      adenoma. The tumor showed two distinct heterologous components, a ductal
      carcinoma and an osteosarcoma. The latter has not been described so far in such
      tumors arising in pleomorphic adenoma of parotid gland.

PMID- 8157326
TI  - Gonadal teratomas: a study of 206 cases.
AB  - Total 206 gonadal teratomas were diagnosed in Christian Medical College and
      Hospital, Ludhiana from January 1980 to December 1990. 182 of them were in ovary
      and other 24 in testis. Majority of them i.e. 45.1% of ovarian and 45.8% of
      testicular lesions were seen in third decade. On gross examination 161 (88.4%) of
      ovarian tumours were cystic one (0.5%) was completely solid, while 20 (10.9%)
      showed solid as well as cystic areas. Majority (93.9%) of them were mature
      teratomas; 27 (14.8%) being dermoid cysts. In testicular lesions 22 (91.7%) were
      solid as well as cystic type and 2 (8.3%) were purely solid. Twenty (83.3%) of
      them were immature and only 4 (16.7%) lesions showed benign histology.

PMID- 8157327
TI  - Malignant teratoid medulloepithelioma: a case report.
AB  - A case report "Malignant Teratoid Medulloepithelioma" is herewith presented for
      its rarity. Medulloepitheliomas are embryonic tumors occurring infancy and are
      probably congenital. Occasionally they show glial tissue and cartilage.

PMID- 8157328
TI  - Laboratory diagnosis of tuberculosis: use of ELISA and PCR.

PMID- 8157330
TI  - New type of cholera.

PMID- 8157329
TI  - Transcatheter occlusion of atrial septal defect and patent ductus arteriosus: now
      a reality in India.

PMID- 8157331
TI  - Anganwadi worker's participation in rural newborn care.
AB  - Anganwadi worker was involved in rural newborn care as a link between a dai and a
      health worker. She was trained to ensure that, (i) borderline LBW/preterm baby
      was kept warm at home and (ii) a very small baby was referred to hospital. The
      training was conducted during routine monthly meetings and cost of equipping each
      anganwadi worked out to be Rs 110. Newborn survival, infant survivals and overall
      MCH performance improved. Thus, newborn care formed an ideal entry point into MCH
      activities.

PMID- 8157332
TI  - Fecal sodium and potassium losses in low birth weight infants.
AB  - We measured 24-hour fecal losses of sodium (Na) and potassium (K) in immediate
      post natal period of preterm neonates to determine the role of this route in the
      electrolyte imbalances seen in such infants. The values from preterm infants were
      compared to a group of age matched term infants. Eleven studies were done on
      unfed extremely low birth weight infants (group I, birth weight < 1200 gms),
      seven on fed preterm infants (group II, birth weight 1201-2500 gms) and nine on
      fed term infants (group III, birth weight 2501-4000 gms). Measured and derived
      variables compared between the groups were 24 hour fecal volume, total fecal
      electrolyte contents, Na or K lost per kg of body weight and per gm. of stool and
      Na or K losses as percent of intake. Although 24 hour fecal volume was lowest in
      group I, none of the variables related to Na differed between groups I and II
      whereas all of them were significantly lower in group I when compared with group
      III. Groups II and III differed only in terms of Na loss/gm stool which was lower
      in the previous group. Conversely K loss/gm of stool was significantly higher in
      group I when compared with both groups II and III and the only variable that
      differed between groups II and III was a higher fecal K content as fraction of
      intake. Fecal K/Na ratio was highest in group I, and decreased progressively with
      advancing gestational age, whereas creatinine clearance was lowest in group I and
      increased along with gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157333
TI  - Successful induced non-puerperal lactation in surrogate mothers.
AB  - Ten surrogate mothers seen between 1986-91 were encouraged to breast-feed their
      babies varying in age between 8 days to 5 months. All the 10 surrogate mothers
      had experienced pregnancy and child birth in the past. The lactational gap varied
      from 1 year to 16 years. Presence of milk was noted on 3rd to 8th day after
      attempting induced lactation in 5 mothers. No milk was seen on manual expression
      of the nipple even after 2 weeks in the other 5 surrogate mothers. Two mothers
      achieved complete breast-feeding and they fed their babies for 2 years. Three
      mothers could achieve partial lactation and these mothers fed for 1 year or more.
      All these 5 babies registered satisfactory growth.

PMID- 8157335
TI  - Nomograms of fetal nuchal fold thickness for early detection of Down syndrome.
AB  - A prospective study was undertaken in North India to find the normative data on
      the nuchal fold thickness of randomly selected 150 fetuses between 16-22nd week
      of gestation. The data revealed that the width of nuchal fold thickness ranged
      between 2-5 mm. The mean for 16-18, > 18-20, and > 20-22 week's gestation was 2.6
      +/- 0.2, 3.8 +/- 0.9, and 4.0 +/- 0.8 mm respectively. In one fetus nuchal fold
      thickness was 6mm at 18 weeks (> 2SD above the normal value) and thus Down
      Syndrome was suspected. This was later confirmed by amniocentesis and
      karyotyping.

PMID- 8157334
TI  - An epidemiological study of congenital malformations in newborn.
AB  - In a prospective study of 3000 consecutive deliveries (14 twin deliveries), the
      rate of congenital malformation was reported to be 27.20 per 1000 births (82 out
      of 3014). No significant difference was observed in the frequency of congenital
      malformation in urban rural status, in different religion and caste, and in male
      female babies. An increase in frequency was seen in advanced maternal age and in
      primi and fourth gravida mothers. A number of environmental factors studied, such
      as use of different tooth powders, type of drinking water, different cooking
      vessels, associated vitamin deficiencies did not seem to influence the prevalence
      of birth defects significantly. The factors which significantly increased the
      rate of congenital malformation were consanguinity in parents, heredofamilial
      history of malformations, presence of hydramnios, maternal febrile illness in
      first trimester, past history of abortion and history of progesterone intake
      during pregnancy.

PMID- 8157336
TI  - Prevention of tuberculosis in infancy.
AB  - A prospective study was conducted on 185 consecutive hospitalized cases of
      tuberculosis below the age of one year, and 41 mothers comprised half of the 83
      contacts detected. Maternal and infant infection was analyzed to determine
      whether the disease could have been prevented under the existing medico-socio
      economic conditions. Most mothers had delayed diagnosis and extensive disease.
      Earlier imperfect courses of chemotherapy were not uncommon. Ten mothers were
      sputum-positive for acid-fast bacilli. The concerned medical personnel failed to
      give proper advice with respect to chemoprophylaxis and surveillance of infants.
      Majority of infants had progressive pulmonary and disseminated disease although,
      41% of them were BCG vaccinated. A practical strategy in the Indian context for
      the management of tuberculosis in the mother-infant pair is outlined.

PMID- 8157337
TI  - Pyogenic meningitis in Ahmedabad.
AB  - One hundred and thirty five cerebrospinal fluid (CSF) samples from children
      clinically diagnosed Pyogenic meningitis (in and around Ahmedabad) were subjected
      to physical, bacteriological, cytological and biochemical examinations. It was
      found that all CSF specimens were turbid, the culture positivity varied form
      12.12 to 56%. The highest percentage was found in children of less than one year
      of age. The average percentage of culture positivity was 28.68%. The result of
      gram stain was more than that of cultural examination. Gram stain of CSF was
      specific, accurate and highly valuable in the diagnosis of pyogenic meningitis.
      Among gram positive organisms isolated, Staphylococcus aureus was highest (8.8%)
      followed by Diplococcus pneumoniae (3.7%), but Klebsiella was predominant (6.6%)
      among gram negative bacilli. Staph. aureus was 100% sensitive to erythromycin,
      gentamycin, kanamycin and ampicillin. The results of cytological and biochemical
      tests correlated (67.1%). There was increase in polymorphs and protein, sugar
      levels decreased.

PMID- 8157338
TI  - Neuropsychological abnormalities following CNS prophylaxis in children with acute
      lymphatic leukemia.
AB  - The pattern and prevalence of neuropsychological abnormalities in children
      receiving combination CNS prophylaxis (2000 rads cranial irradiation and
      intrathecal methotrexate) during therapy for acute lymphoblastic leukemia (ALL)
      were studied. Thirty five children (25 boys) in the age group 5-15 years (mean
      9.3) with no evidence of CNS leukemia were included and 20 age matched normal
      siblings served as controls. Neuropsychological parameters of general
      intelligence (Malin's modification of WISC test); attention and concentration
      (colour cancellation test); memory (modified PGI memory test) and visuomotor
      perception (Bender Gestalt test) were evaluated at least 6 months after CNS
      prophylaxis. Six (17.1%) patients had mean intelligence quotients (IQ) less than
      85, while all controls had IQ > 85 (p < 0.05). The mean IQ of the patient
      population (93.4 +/- 11.9) was significantly lower than the control group (107 +/
      8.4) (p < 0.001). Scores on the colour cancellation test were lower in the
      patients as compared to controls (148.7 +/- 27.7 versus 184.9 +/- 23.9; p <
      0.01). The mean memory quotient in the patient population was also lower than in
      controls (74.5 +/- 12 versus 93.6 +/- 9.2; p < 0.001). Scores on the Bender
      Gestalt test did not show a significant difference. The presence of significant
      neuropsychological abnormalities in patients of ALL indicates the need for
      modification of the schedule of CNS prophylaxis. A comprehensive psychometric
      evaluation at regular intervals is essential for longterm rehabilitation.

PMID- 8157340
TI  - Lateralised sympodia.

PMID- 8157339
TI  - Nutritional vitamin B12 deficiency in infancy.

PMID- 8157341
TI  - Immunoblastic sarcoma arising in angioimmunoblastic lymphadenopathy.

PMID- 8157342
TI  - Gangrene in newborn.

PMID- 8157343
TI  - Pycnodysostosis with anemia.

PMID- 8157344
TI  - Alveolar soft tissue sarcoma of maxillary-ethmoid complex.

PMID- 8157345
TI  - Management of childhood asthma.

PMID- 8157346
TI  - Cotton-ball phytobezoar simulating oesophageal atresia.

PMID- 8157347
TI  - Varicella induced thrombocytopenia.

PMID- 8157348
TI  - Chylolymphatic mesenteric cyst: an unusual abdominal mass in a newborn.

PMID- 8157349
TI  - Soft-tissue sarcomas in adults--current treatment strategies.

PMID- 8157350
TI  - Reproductive history and cancer of the biliary tract in women.
AB  - Although reproductive factors have been shown to be related to the composition of
      bile and functioning of the biliary system, their relationship with biliary tract
      cancer has not been studied in detail. Between 1984 and 1987 we conducted a case
      control study of 75 women with cancer of the biliary tract and 252 controls from
      the general population. An interviewer-administered questionnaire was used to
      collect information on reproductive history. The information was obtained from
      the responders themselves (direct response) or from relatives (indirect
      response). Our results indicate that younger age at menarche, early age at first
      pregnancy, higher number of pregnancies and prolonged fertility may enhance the
      risk of cancer of the biliary tract. Overall, increased exposure to endogenous
      oestrogens and progesterone constitutes a higher risk.

PMID- 8157351
TI  - Time trends of lung and larynx cancers in Italy.
AB  - During the period 1970-1989, age-adjusted mortality rates for lung cancer in
      Italy increased by more than 50%, while rates for larynx cancer in males
      decreased by approximately 13%. This study aims to interpret this difference,
      which seems to contradict the finding that cigarette smoking is a common major
      risk factor for both lung and larynx cancer. To this end, we jointly analyzed the
      time trends of incidence, survival and mortality. We first examined survival data
      taken from the population-based Lombardy Cancer Registry (northern Italy). Based
      on data referring to 880 incident cases of larynx cancer, diagnosed during the
      period 1976-1987, we estimated a 3% annual increase in relative survival. By
      contrast, no significant period effect was observed for survival rates of 2,259
      incident cases of lung cancer. National incidence rates were estimated using
      official mortality data and the above-described survival data. Age-adjusted
      estimated incidence rates increased, from 1970 to 1989, for both cancer sites:
      +55% for male lung, +56% for female lung, and +22% for male larynx. Moreover, the
      patterns of birth-cohort effect, which are diverging for mortality, are nearly
      parallel with regard to incidence. This analysis suggests that a substantial
      improvement in survival of larynx cancer patients may largely explain the
      differences in mortality trends for cancer of lung and larynx.

PMID- 8157352
TI  - The effect of vitamin and mineral supplementation on esophageal cytology: results
      from the Linxian Dysplasia Trial.
AB  - The population of Linxian in China has one of the world's highest rates for
      esophageal/gastric cardia cancer, as well as documented nutritional deficiencies.
      To determine whether dietary supplementation with a multi-vitamin multi-mineral
      preparation could reduce the risk of esophageal cancer and favorably influence
      precursor lesions, 3,318 individuals age 40-69 with cytologically determined
      grade 1 or grade 2 esophageal dysplasia were randomly assigned to receive either
      an active multi-vitamin multi-mineral supplement or a placebo. Pills were
      distributed at monthly visits and incident cancers or deaths were recorded. At 30
      and 72 months subsequent to randomization all living participants without a known
      incident cancer were asked to undergo repeat cytological examination of their
      esophagus. Based on these procedures participants were classified as having no
      dysplasia, dysplasia grade 1, dysplasia grade 2 or near cancer dysplasia.
      Diagnoses of cancer were based on the cytology findings plus available
      histologic, radiologic and clinical materials. At the end of the study there was
      little overall difference in cumulative risk of esophageal cancer between those
      receiving vitamin/mineral supplementation and those receiving placebo. There was,
      however, a significant increase in reversion to non-dysplastic cytology among the
      group receiving the active treatment. The odds of not having any dysplasia at the
      two post-randomization screens was 1.23 times higher in the active treatment
      group than in the placebo group. Within each treatment group higher categories of
      dysplasia were associated with higher rates of cancer.

PMID- 8157353
TI  - Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical
      differences.
AB  - Seventy-seven pancreatic adenocarcinomas (60 Spanish and 17 Italian) were tested
      for Ki-ras gene mutations by analysis of polymerase chain reaction amplified
      sequences. Mutations involving codon 12 (GGT; gly) were detected in 16 Italian
      and 46 Spanish cases (80.5% in total). All Italian mutations involved the second
      base and were G to A transitions (GAT; asp) in 8 cases and G to T transversions
      (GTT; val) in the remaining 8. Forty-two Spanish mutations were characterized.
      Thirty-eight were at the second and 4 at the first base: asp in 24 cancers, val
      in 14, arg (CGT) in 2 and cys (TGT) in 2. Previous European studies and our
      present data show that 149 of the 186 pancreatic cancers harbored a codon 12 Ki
      ras mutation (80%), the large majority affecting the second base (73%), with a
      transitions/transversions ratio of 1.3:1. However, the mutational pattern of
      cancers of the different European countries shows remarkable differences, both in
      the site of the mutation (first or second base) and in the ratio of transitions
      over transversions. Moreover, a significant subgroup of pancreatic carcinomas do
      not harbor Ki-ras mutations. The classification of pancreatic cancers, according
      to the presence or absence, and type of Ki-ras mutation, may be of importance in
      epidemiological studies. A critical reappraisal of existing epidemiological data,
      through a retrospective genotypic study using paraffin-embedded cancer samples,
      may reveal significant correlations with specific genotoxic agents.

PMID- 8157354
TI  - Molecular analysis of chromosome 1 abnormalities in human gliomas reveals
      frequent loss of 1p in oligodendroglial tumors.
AB  - Alterations of the short arm of chromosome 1 are recurrently found in cytogenetic
      analysis of malignant gliomas, and deletions of 1p36-p32 region characterize at
      least the higher-grade tumors, glioblastoma multiforme. Molecular analysis of
      tumor-derived and normal genomic DNA from 57 cases of gliomas, using a panel of
      chromosome 1-specific DNA probes showed LOH in 16 tumors. Allelic losses on 1p
      were primarily restricted to glioblastoma multiforme (2/11) and to tumors with a
      major oligodendroglial component: grade II oligodendrogliomas (6/6), grade III
      anaplastic oligodendrogliomas (5/6) and grade II-III mixed oligo-astrocytomas
      (2/3). Losses for 1q markers were detected in only 1 tumor (glioblastoma
      multiforme). Our data suggest that anomalies of 1p primarily characterize
      oligodendrogliomas, whereas they are rare events in astrocytic tumors and
      indicate that a tumor-suppressor gene on 1p36-p32 is involved in the development
      of brain tumors with oligodendroglial differentiation.

PMID- 8157355
TI  - The genotypes and prognostic significance of human papillomaviruses in cervical
      cancer.
AB  - An integrated study on the role of human papillomaviruses (HPV) in cervical
      cancer has been conducted. Out of a total of 433 cases of cervical cancer, HPV
      DNA was detected in 342 (79%) using the polymerase chain reaction (PCR). The
      incidence of HPV infection was not significantly related to histological types,
      although a lower incidence was noted in adenocarcinoma cases. The incidence of
      lymph node (LN) metastasis in adenosquamous carcinoma (55.6%) was significantly
      higher than in squamous cell carcinoma (SCC) and adenocarcinoma. HPV 16 was
      detected significantly more often in SCC than in adenocarcinoma. In contrast, HPV
      18 was detected more often in adenocarcinoma than in SCC. As a whole, pelvic LN
      metastases were found in 24.3% of HPV+ cases, significantly higher than 11% of
      HPV- cases. However, the significant association of HPV-DNA with LN metastasis
      was only noted in stage I but not stage II. As far as histological types were
      concerned, the incidence of positive LN was: HPV+ SCC > HPV- SCC (p < 0.01),
      whereas HPV- adenocarcinoma > HPV+ adenocarcinoma (p = 0.12). Genotypes of HPV
      did not have any effect on nodal status. The presence of types of HPV were not
      associated with tumor size and distribution of clinical stage. Our results
      suggest that the prognostic significance of HPV-DNA on nodal status is dependent
      on histological types while the genotypes of HPV cannot account for prognostic
      significance in cervical cancer.

PMID- 8157356
TI  - Multiple loci on human chromosome 11 control tumorigenicity of BK virus
      transformed cells.
AB  - BK virus (BKV) is a human papovavirus that readily transforms rodent cells, but
      not human cells, to a neoplastic phenotype, suggesting that tumor-suppressor
      functions expressed in human cells control BKV oncogenicity. Transfer of a normal
      human chromosome 11 to BKV-transformed mouse cells suppresses the malignant
      phenotype. In this report we map the regions of chromosome 11 involved in tumor
      suppression. Transfer of chromosome 11 to the BKV-transformed hamster cell line
      HKBK produces monochromosomic hybrids retaining only portions of the transferred
      human chromosome. We have compared the tumorigenicity of the hybrids with the
      molecular mapping of chromosome 11 retained regions. This analysis indicated that
      3 regions of human chromosome 11, 11p15.5, 11p13 and 11q13, cooperate in tumor
      suppression. However, 11q13 seems the most important, since all the HKBK/H11
      induced tumors analysed had lost this region, whereas 11p15.5 and 11p13 were
      sometimes retained. The chromosomal regions identified in this study are deleted
      in several types of human tumors, suggesting that the BKV transformation system
      specifically detects tumor-suppressor genes on chromosome 11 that are involved in
      human oncogenesis. This model may be of use in isolating and cloning such genes.
      The results of this report raise the possibility that BKV may have a synergistic
      tumorigenic effect in human cells where tumor-suppressor genes controlling its
      oncogenic potential are inactivated.

PMID- 8157357
TI  - The anti-tumor arotinoid Ro 40-8757 protects bone marrow from the toxic effects
      of 5-fluorouracil.
AB  - Combination therapy with 5-fluorouracil (5-FU) and the arotinoid Ro 40-8757
      (mofarotene) of established chemically induced mammary tumors in rats was
      examined. The cytotoxic drug was administered weekly and Ro 40-8757 was given
      daily. The dose of Ro 40-8757 used in this study did not have an effect on tumor
      burden but, in combination with 5-FU, significantly enhanced the reduction in
      tumor burden and tumor number. In order to determine if Ro 40-8757 had a
      protective effect on 5-FU-treated animals, several studies were performed with
      non-tumor-bearing mice. The 5-FU was given once a week for 3 weeks at a dose that
      was lethal only after the third administration. When this treatment was combined
      with Ro 40-8757 given 5 times/week, approximately 50% of the mice survived.
      Examination of the progenitor cell contents of femur and spleens of treated mice
      indicated that the protective effect of Ro 40-8757 was manifested at the
      primitive hemopoietic progenitor cell level. Studies with murine bone marrow
      cells and human breast-cancer cell lines in vitro demonstrated that there was no
      interaction between the 2 drugs at the cellular level, indicating that the
      arotinoid does not enhance the ability of cells to metabolize 5-FU. This
      protective effect of the arotinoid makes it a useful potential partner for
      combination therapy with 5-FU.

PMID- 8157358
TI  - Expression of MUC1, MUC2, MUC3 and MUC4 mucin mRNAs in human pancreatic and
      intestinal tumor cell lines.
AB  - We examined the steady-state expression levels of mRNA for the MUC1, MUC2, MUC3
      and MUC4 gene products in 12 pancreatic tumor cell lines, 6 colon tumor cell
      lines, and one ileocecal tumor cell line. The results showed that 10 of 12
      pancreatic tumor cell lines expressed MUC1 mRNA and that 7 of these 12 lines also
      expressed relatively high levels of MUC4 mRNA. In contrast, MUC2 mRNA was
      expressed at only low levels and MUC3 was not detected in the pancreatic tumor
      cell lines. All 7 intestinal tumor cell lines examined expressed MUC2, and 5 of 7
      expressed MUC3; however only one expressed significant levels of MUC1 and 2
      expressed low levels of MUC4 mRNA. This report of high levels of MUC4 mRNA
      expression by pancreatic tumor cells raises the possibility that mucin
      carbohydrate epitopes defined by antibodies such as DuPan 2 may be expressed on a
      second mucin core protein produced by pancreatic tumor cells.

PMID- 8157359
TI  - Quercetin enhances transforming growth factor beta 1 secretion by human ovarian
      cancer cells.
AB  - Our study demonstrates that quercetin (Q)-induced growth-inhibitory activity in
      ovarian cancer cells may be mediated by modulation of transforming growth factor
      beta 1 (TGF beta 1) production. We used the OVCA 433 cell line which is very
      sensitive to the anti-proliferative effect of Q and expresses high-affinity, low
      capacity TGF beta 1 receptors. Conditioned medium (CM) from Q-treated cells is
      able to displace 125I-TGF beta 1 from binding to its receptor; moreover Q (10
      microM) increases TGF beta 1 activity in CM in a time-dependent fashion starting
      after 4 hr and reaching a maximum by 24 hr of Q treatment. Q-induced growth
      inhibition is reversed by a neutralizing anti-TGF beta 1 MAb both in OVCA 433 and
      in a clonogenic assay of cells from a primary ovarian tumor. Q-induced increase
      of TGF beta 1 activity in CM is specific since other anti-proliferative
      compounds, such as Dexamethasone, which is as active on the cell cycle as Q, had
      no effect on TGF beta 1 secretion. Northern-blot analysis of TGF beta 1 mRNA
      levels at various times of Q (10 microM) exposure revealed that there was no
      increase, suggesting that regulation of TGF beta 1 occurs at posttranscriptional
      levels.

PMID- 8157360
TI  - Acquisition of immunogenicity by AKR leukemic cells following DNA-mediated gene
      transfer is associated with the reduction of constitutive reactive superoxide
      radicals.
AB  - We have employed the DNA-mediated gene transfer method to introduce the allogenic
      major-histocompatibility-complex(MHC)-class-I gene H-2Kb into the K36.16 tumor
      cells, H-2k, in order to generate tumor-specific immunity. The acquisition of
      immunogenicity by the H-2Kb-transformed clones following gene transfer is
      associated with the reduction of constitutive reactive superoxide radicals. When
      the levels of cellular superoxide for the H-2Kb-positive immunogenic clones were
      determined, they were significantly lower (30 to 60%) than that of the parental
      K36.16 tumor cells. This reduction of superoxide in the H-2Kb-transformed cells
      was associated with a significant increase in the level of Cu-Zn superoxide
      dismutase (SOD) and GPX I, together with a reduction in the DNA-binding form of
      the NF-kappa B transcription factor. The K36.16 parental tumor cells were also
      found to be relatively more resistant to the cytotoxic effects of hydrogen
      peroxide in vitro. To further support the role of superoxide anion radicals in
      tumorigenesis, in vivo depletion of glutathione promoted the tumorigenicity of
      the H-2Kb-transformed clones in (AKR/J x C57BL/6/J) F1 mice, whereas SOD was able
      to reduce their tumorigenicity. In addition, the presence of R-sulfoxine (BSO) in
      spleen-cell cultures in vitro abolished the ability of the immune lymphocytes to
      develop into tumor-specific cytotoxic T lymphocytes (CTL). These observations
      support the concept that oxidative processes in tumor cells may have a strong
      influence on the host response against tumors.

PMID- 8157361
TI  - Effects of testosterone, dihydrotestosterone and estrogen on 3,2'-dimethyl-4
      aminobiphenyl-induced rat prostate carcinogenesis.
AB  - Post-initiation effects of testosterone propionate (TP), alpha
      dihydrotestosterone (DHT) and ethinyl estradiol (EE) on 3,2'-dimethyl-4
      aminobiphenyl (DMAB)-prostate carcinogenesis in F344 rats have been investigated
      by administration of each hormone individually or either androgen in combination
      with EE. DMAB plus TP resulted in induction of invasive adenocarcinomas in the
      lateral and anterior prostate and seminal vesicles, as shown in a previous study,
      whereas DHT did not exhibit any positive modulation potential. Administration of
      EE together with TP produced increased carcinoma incidence in the lateral and
      anterior prostate, from 17 and 28% to 70% and 80%, respectively. Dorsal prostate
      tumors, all of the non-invasive in situ type, were also evident in 30% of animals
      receiving both TP and EE. Rats treated with DHT plus EE, however, did not develop
      tumors. Our experiment thus provides evidence that estrogen may play an important
      role in prostate carcinogenesis.

PMID- 8157362
TI  - The Epstein-Barr virus latent membrane protein-1 (LMP1) induces interleukin-10
      production in Burkitt lymphoma lines.
AB  - Human interleukin-10 (h-IL-10) is a pleiotropic cytokine with stimulatory
      activity on B-lymphocytes. Recent evidence indicates that infection with Epstein
      Barr virus (EBV) induces h-IL-10 production in B-cells and that this cytokine may
      contribute to EBV-induced B-cell transformation. It is not known whether h-IL-10
      induction by EBV correlates with distinct phenotypic features of the infected
      cells or with the expression of particular viral genes. We have approached these
      questions by investigating the expression of h-IL-10 mRNA in a panel of B-cell
      lines including: in vitro EBV-transformed lymphoblastoid cell lines (LCLs), EBV
      carrying Burkitt lymphoma (BL) lines, EBV-negative BL lines and their sublines
      infected with different EBV strains, or transfected with the transformation
      associated viral gene. h-IL-10 mRNA was detected by reverse-transcriptase
      assisted (RT)-PCR in a subset of EBV-negative BLs and in all EBV-positive BL
      lines and LCLs investigated except Daudi. This cell line carries an EBV nuclear
      antigen (EBNA)-2 gene-defective virus strain. h-IL-10 mRNA was induced by
      conversion of 3 EBV-negative and h-IL-10-negative BL lines (BL41, BL47 and BL49)
      with the transforming, B95.8-derived EBV strain. P3HR-I virus convertants that do
      not express the viral EBNA-2 and the EBV latent membrane protein (LMP)-1, and
      fail to progress towards a LCL-like cell phenotype, showed no evidence of h-IL-10
      up-regulation. Expression of LMP1 was sufficient to induce h-IL-10 mRNA in
      transfected sublines of the EBV-negative DG75 and BL41 cell lines, whereas
      expression of EBNA1, 2, 5, or 6 had no effect. h-IL-10 was detected in the
      culture supernatants of the LMP1 transfectants by specific ELISA assays. The
      present findings confirm the role of LMP1 in the transactivation of a wide
      variety of cellular genes which may be involved in EBV-induced B-cell
      transformation.

PMID- 8157363
TI  - Mechanism of inhibition of FaDu hypopharyngeal carcinoma cell growth by
      tetraphenylphosphonium chloride.
AB  - Cationic phosphonium salts are interesting because they inhibit the proliferation
      of carcinoma cells more than untransformed epithelial cells in vitro. This
      differential anti-proliferative effect has been used to identify phosphonium
      salts and other lipophilic cations that later demonstrated effects in animals.
      Using 6 carcinoma-derived and 2 untransformed epithelial cell lines,
      tetraphenylphosphonium chloride (TPP) and other cationic aryl phosphonium salts
      (CAPS) demonstrated a growth inhibition pattern similar to that of cation
      rhodamine 123, suggesting that CAPS may inhibit mitochondrial function. We tested
      this hypothesis for the effect of phosphonium salt TPP on FaDu human
      hypopharyngeal carcinoma cells. TPP inhibited the proliferation of FaDu carcinoma
      cells at submicromolar concentrations. Uptake of 3H-TPP by FaDu cells was
      partially inhibited in medium containing high K+ and fully inhibited by
      valinomycin in this medium, indicating that TPP accumulates preferentially in
      mitochondria, and to a lesser extent in the cytoplasm. FaDu cells exposed to TPP
      exhibited damage to mitochondrial inner membranes, reduced ATP/ADP ratios,
      decreased oxygen uptake rates and decreased mitochondrial membrane potentials.
      The treated cells secreted lactate more rapidly than untreated controls and
      exhibited hypersensitivity to 2-deoxyglucose, an inhibitor of glycolysis. TPP's
      antimitochondrial effects apparently enhance cytoplasmic glycolysis. In
      conclusion, TPP inhibits FaDu carcinoma cell growth by inhibiting mitochondrial
      respiration and ATP synthesis. Cationic phosphonium salts that inhibit carcinoma
      cell growth through antimitochondrial effects might be used to treat solid tumors
      without the risk of secondary tumors associated with agents affecting nuclear
      DNA.

PMID- 8157364
TI  - Cytoreductive effects of anti-transferrin receptor immunotoxin in a multicellular
      tumor spheroid model.
AB  - We have evaluated the sensitivity to immunotoxins (IT) of monolayer and of 200
      250 microns multicellular tumor spheroid (MTS) cultures obtained with human
      breast (MCF7) and glioblastoma (U118) tumor cells and with rat glioblastoma (9L)
      cells. Monolayer MCF7 and U118 cells were highly sensitive to antitransferrin
      receptor (anti-TfnR) ricin A chain (RTA)-IT (Tfn-RTA and MAb OKT9-RTA) treatment
      in the presence of the intracellular RTA-IT enhancing agent human serum albumin
      monensin (HSA-Mo) conjugate. A 790- to 2000-fold higher concentration of anti
      TfnR IT was instead required to reduce by 50% the volume of individually treated
      MCF7 spheroids, as evaluated by applying the Gompertz growth model. Monolayer 9L
      cells showed 230- to 5700-fold lower sensitivity to Tfn-RTA IT than MCF7 and U118
      monolayers, yet 9L spheroid cells were almost as sensitive to anti-TfnR IT as
      monolayer 9L cultures. Binding studies performed with [125I]-Tfn and FITC
      labelled anti-TfnR MAb revealed that 9L monolayers and MTS expressed 4.1-fold and
      8.8-fold lower amounts of TfnR than MCF7 monolayers and MTS, respectively.
      However, Tfn bound to TfnR sites of 9L and of MCF7 cells with comparable
      affinity. Experiments carried out with the diphtheria toxin mutant CRM107 linked
      to Tfn confirmed the pattern observed with RTA-IT. Monolayers and spheroids
      showed no considerable differences in sensitivity to ricin toxin. Collectively,
      these results indicated that the efficacy of IT against 3-D tumors is heavily
      influenced by the number of target Ag expressed by the tumor cells, as well as by
      the affinity of IT/toxin-cell interaction.

PMID- 8157365
TI  - Effect of protein kinase C inhibitors on invasiveness of human melanoma clones
      expressing different levels of protein kinase C isoenzymes.
AB  - The involvement of protein kinase C (PKC) in the mechanism of chemotaxis and
      invasiveness of human melanoma has been studied in 6 clones of 665/2 cell line
      characterized by a different integrin profile, differentiation grade and in vitro
      invasive ability. The levels of total protein kinase C activity revealed a direct
      correlation with the chemotactic and invasive ability of these clones. Protein
      kinase C inhibitors, sphingosine and staurosporine, reduced chemotaxis and
      invasiveness of the highly invasive clone 2/60, while 1-(5-isoquinolinylsulfonyl)
      2-methylpiperazine (H7) was ineffective. Immunofluorescence analysis revealed
      high levels of protein kinase C alpha in clone 2/60, while the less invasive
      clone 2/21 expressed low levels of protein kinase C alpha and beta, but
      surprisingly appreciable levels of protein kinase C gamma. Downregulation with
      phorbol 12-myristate 13-acetate (TPA) did not affect invasiveness of clone 2/60
      unless the compound was present during the assay. H7 strongly increased
      invasiveness of clone 2/21 and was able to reverse the inhibitory effect of TPA
      on clone 2/60. Preliminary experiments showed higher levels of diacylglycerol in
      clones with lower protein kinase C, suggesting a constitutive downregulation of
      the enzyme in low invasive clones. Our results support a role for protein kinase
      C in the invasion process, but point out the complexity of the mechanism which
      might involve the proteolytic fragment of the enzyme, protein kinase M.

PMID- 8157367
TI  - Infective dermatitis among patients with ATL in Japan.

PMID- 8157366
TI  - Suppressive effect of recombinant human Cu, Zn-superoxide dismutase on lung
      metastasis of murine tumor cells.
AB  - The inhibitory effect of recombinant human Cu++Zn++superoxide dismutase (rhSOD)
      on metastasis of tumor cells in the mouse was investigated. In an experimental
      pulmonary metastasis model employing Meth A cells as inoculum, significant
      inhibition of metastasis was obtained by intravenous pre- and post-administration
      of rhSOD. An inhibitory effect of rhSOD was also observed in a spontaneous
      pulmonary metastasis model with 3LL cells as the inoculum. rhSOD was not observed
      to have any significant effects on the platelet-aggregating activity of tumor
      cells, the adhesiveness of tumor cells to vascular components (endothelial cells,
      laminin and type-IV collagen), or the growth of tumor cells either in vitro or in
      vivo. However, rhSOD suppressed invasion of Meth A and 3LL cells into Matrigel
      (an artificially reconstituted basement membrane of collagen, laminin and heparan
      sulfate) in the presence of hypoxanthine and xanthine oxidase, in vitro producers
      of superoxide. Thus, the present study shows that rhSOD is able to inhibit both
      experimental and spontaneous pulmonary metastasis, possibly through the
      suppression of tumor cell invasion into the extracellular matrix.

PMID- 8157368
TI  - Evidence that the effect of bicycle exercise on blood mononuclear cell
      proliferative responses and subsets is mediated by epinephrine.
AB  - The present study was designed to test the hypothesis that the exercise-induced
      changes in blood mononuclear cell (BMNC) subsets, BMNC proliferative responses
      and lymphokine activated killer (LAK) cell activity are mediated by increased
      epinephrine concentrations. Healthy male volunteers 1) exercised on a bicycle
      ergometer (75% of VO2max, 1 h) and 2) on another day were given epinephrine as an
      intravenous infusion to obtain plasma epinephrine concentrations comparable with
      those seen during exercise. Blood samples were collected in the basal state,
      during the last minutes of exercise or epinephrine infusion and 2 h later. During
      both perturbations the %CD3+ and %CD4+ T cells declined and the %CD16+ NK cells
      increased. Two h afterwards the CD14+ monocytes increased, while no changes were
      observed in %CD8+ T cells or %CD20+ B cells. The phytohemagglutinin (PHA)
      response declined during both epinephrine infusion and exercise experiments. The
      changes in interleukin-2 (IL-2) effect on proliferation and cytotoxic activity
      (LAK cell activity) were more pronounced in exercise experiments than during
      epinephrine. Exercise and epinephrine caused increase in concentrations of
      lymphocytes and neutrophils, but the changes were more pronounced in exercise
      experiments. The results indicate that, in response to physical exercise, the
      rise in plasma epinephrine may contribute to the changes in cellular immunity.

PMID- 8157369
TI  - Red blood cell function in hypoxia at altitude and exercise.
AB  - Oxygen transport by red blood cells is regulated by erythropoiesis and Hb-O2
      affinity. The O2 carrying capacity is characterized by changes in hematocrit, red
      blood count or the mass of circulating red blood cells. Erythropoiesis is
      controlled by the hormone erythropoietin, which induces slow changes of the O2
      transport capacity. The Hb-O2-affinity is modified mainly by pH and 2,3-DPG.
      Despite their apparently diverse effects e.g. in hypoxia at high altitude, a
      compromise seems to be adopted optimizing both arterial O2-loading and peripheral
      O2-unloading. In contrast to erythropoiesis, adjustments of the Hb-O2-affinity
      occur fast and allow rapid adjustments of O2-binding and release. In the intact
      organism the significance of changes in Hb-O2-affinity for tissue oxygen supply
      relative to adjustments of cardiac output, microcirculation and O2-transport
      capacity is not completely understood yet, but beneficial effects were
      demonstrated in isolated organs. It is, however, the least energy-demanding way
      of optimizing tissue O2-supply, which might be of significance in extreme
      situations. In severe hypoxia adjustments of both, hematocrit and Hb-O2-affinity,
      are insufficient to maintain tissue O2-supply. Alterations of Hb-O2-affinity are
      also insufficient to compensate for severe anemia.

PMID- 8157370
TI  - Effect of inhibition of hepatic fatty acid oxidation on metabolic and hormonal
      responses to exercise in rats.
AB  - The purpose of the present study was to assess the effects of 2-mercaptoacetate
      (MA), an inhibitor of hepatic fatty acid oxidation, on the metabolic and
      pancreatic hormone response to a prolonged (3 h) swimming exercise. All rats were
      first adrenodemedullated and were either submitted for 3 weeks to a normal (5%
      fat) or a medium-fat diet (MF; 18% fat). After being submitted to an exercise
      swimming habituation programme for one week, rats under both dietary conditions
      were either injected with a bolus dose of MA (600 mumol/kg; ip) or with a saline
      solution. MA and saline injected rats were either sacrificed after a 3-h swimming
      exercise or after a 3-h resting period. Administration of MA was associated with
      a lower level of beta-hydroxybutyrate after exercise in rats fed the MF diet,
      higher resting and exercising blood glucose levels in rats fed the MF diet, and
      higher resting and exercising levels of hepatic glycogen in rats fed a normal
      diet. There were, however, no significant effects of MA on free fatty acid,
      insulin, glucagon, epinephrine, and norepinephrine concentrations in both dietary
      conditions either at rest or after exercise. Therefore, the present data do not
      provide any evidence that the administration of MA, an inhibitor of hepatic fatty
      acid oxidation, influences the pancreatic hormonal response to exercise. There
      was also no evidence of a lowering effect of MA on blood glucose levels during
      exercise.

PMID- 8157371
TI  - Myocardial adaptation and weight fluctuation in college wrestlers.
AB  - Myocardial adaptation and weight fluctuation of seven college wrestlers was
      examined during a competitive season. Standard M-mode measurements were used to
      determine left ventricular (LV) end diastolic and end systolic dimensions,
      fractional shortening, LV diastolic posterior wall thickness (DPW), diastolic
      interventricular septal thickness (DIVS), and LV mass (LVM) during preseason
      (test 1) and four months later at the season's end (test 2). The wrestlers'
      qualifying weights ranged from 53.6 to 80.5 kg and each competed in an average of
      17 meets. Systolic and diastolic blood pressure, heart rate, and body weight (BW)
      were measured at both tests. Daily weight records and qualifying weights were
      used to calculate seasonal weight fluctuation as a percentage of the highest
      weight attained between each meet and the wrestler's subsequent qualifying
      weight. Paired t-tests were used to determine differences between tests 1 and 2.
      DPW, DIVS and LVM increased from 8.8 +/- 1.0 to 10.3 +/- 1.0 mm, 7.9 +/- 1.5 to
      9.9 +/- 0.6 mm, and 171.2 +/- 24.3 to 209.7 +/- 12.9 mm3 respectively while BW
      declined from 70.3 +/- 9.2 to 67.1 +/- 9.4 (X +/- SD, p < .01) from test 1 to 2.
      The other variables remained constant across tests. The wrestlers' mean % weight
      fluctuation throughout the season was 7.5 +/- 1.5 ranging from 4.4 to 9.1%. These
      findings suggest that significant increases in myocardial mass occur over the
      course of a competitive wrestling season resulting from increased LV wall
      thickness. The magnitude and cyclic method of weight loss used by wrestlers does
      not appear to prevent myocardial hypertrophy.

PMID- 8157372
TI  - Hypohydration causes cardiovascular drift without reducing blood volume.
AB  - To determine the effect of hydration on cardiovascular drift (i.e.; increased
      heart rate and reduced stroke volume) during exercise in a 21 degrees C
      environment, nine subjects were studied while cycling at 65% of peak oxygen
      consumption when euhydrated and while still hypohydrate, following exercise
      induced dehydration and a 2 h rest/rehydration period. Subjects dehydrated by
      exercising in the heat (32 degrees C) until body weight was reduced 2.5%. On two
      separate occasions following exercise, subjects either received no fluid or
      ingested a volume of water equal to 100% of the fluid lost during exercise.
      Following the 2 h rest/rehydration period, 65 +/- 6% of the ingested water was
      retained and thus the subjects were hypohydrated by 0.9 +/- 0.1%, compared to
      being hypohydrated by 2.8 +/- 0.1% when no fluid was ingested. Despite these
      differences in whole body hydration, blood volume during exercise remained at
      euhydrated levels when hypohydrated by 0.9% and 2.8%. However, the degree of
      cardiovascular drift was graded in proportion to hypohydration. Compared to the
      responses when euhydrated, heart rate was elevated 10 +/- 2 and 18 +/- 2 bt/min,
      whereas stroke volume was reduced 9 +/- 3 and 18 +/- 2 ml/bt, respectively, when
      hypohydrated by 0.9% and 2.8% during the water and no fluid trials (p < 0.05 for
      all comparisons). These observations indicate that cardiovascular drift during
      exercise in a 21 degrees C environment is graded in proportion to hydration and,
      under these conditions, not due to reductions in blood volume.

PMID- 8157373
TI  - Daily variation in step length of trained male runners.
AB  - The purpose of this study was to quantify daily intra-individual variability in
      mean step length, a basic descriptor for the running pattern. Following 60
      minutes of treadmill accommodation, nine trained male subjects (X age = 34.2 yrs
      +/- 7.2, X VO2max = 57.0 +/- 4.8 ml.kg-1.min-1) performed daily (Mon-Fri) 6
      minute treadmill runs at three submaximal speeds (2.68, 3.13 and 3.58 m.s-1) over
      a 4-week period. To minimize extraneous influences, subjects refrained from road
      racing and completed the 20 running sessions (5 d.wk-1.4 weeks for each speed) at
      the same time of day and in the same footwear. Treadmill velocity was calibrated
      for each 6-minute running bout and step length was determined during the last 2
      minutes of each run. Results indicated that mean step length and coefficient of
      variation values were 0.984 m and 2.50% at 2.68 m.s-1, 1.124 m and 2.22% at 3.13
      m.s-1, and 1.254 m and 2.26% at 3.58 m.s-1. Reliability analyses indicated that
      the percentage of variation accounted for in step length across all speeds was
      high and improved very little as test number increased (range = 96% for two days
      vs 99% for five days). Taken together, these findings suggest that when testing
      conditions are controlled, within-subject variability in step length measures
      obtained at multiple submaximal running speeds is small in trained subjects and
      that criterion step length values can be obtained by averaging duplicate
      measurements.

PMID- 8157374
TI  - Development of a scale for use in monitoring training-induced distress in
      athletes.
AB  - In an attempt to identify athletes at risk of training-induced distress, a scale
      was developed using items from the Profile of Mood States (POMS). POMS data were
      collected monthly from 170 varsity college swimmers (70 female, 100 male) during
      four competitive training seasons. The team coaches identified swimmers who
      showed signs of compromised performance in response to intensive training (i.e.,
      distress), and several series of discriminant function analyses were conducted in
      attempts to identify these individuals using POMS scale items. Discriminant
      function equations derived from subsets of items from the entire POMS items pool
      resulted in a mean prediction rate for identifying distressed swimmers of 93.9%
      for men and 100% for women. Seven POMS items which entered the equations most
      frequently served as predictor variables for analyses of a sample of 33 men
      swimmers. Predictions of distress were conducted at each monthly assessment. The
      prediction rate of distress achieved with the 7-item set of POMS items averaged
      69.1%, and this level of accuracy was 37.0% above the chance rate of prediction
      (p < 0.05). In a cross-validation on 29 collegiate track and field athletes, the
      prediction rate of the 7-item scale was 66.7% (p < 0.05). It is concluded that
      the scale developed in this investigation was effective in identifying swimmers
      and other endurance athletes who exhibit signs of distress resulting from
      intensive training.

PMID- 8157375
TI  - The validity and accuracy of blood lactate measurements for prediction of maximal
      endurance running capacity. Dependency of analyzed blood media in combination
      with different designs of the exercise test.
AB  - The effect of using different blood lactate sampling sites in combination with
      different exercise test designs on the validity and accuracy for prediction of
      maximal endurance running velocity was investigated. Ten aerobically all-round
      trained firemen and nine aerobically endurance trained long-distance runners
      performed six differently designed treadmill running blood lactate accumulation
      tests. Each test consisted of five consecutive running periods on a treadmill of
      either 4, 6 or 8 min duration, with a mean increase in running velocity between
      each period of either 0.25 or 0.5 m.s-1. The corresponding treadmill running
      velocity to a lactate concentration of 4.0 mmol.l-1 in capillary and venous
      hemolysed blood and plasma for each running velocity. The mean running velocity
      from a maximal 12 km run for the firemen and a maximal 21 km run for the runners
      served as the reference of maximal endurance running velocity. There were both
      significant (p < 0.001) and similar relationships (r = 0.86-0.94) and no
      difference in mean prediction error between the predicted and measured maximal
      endurance running velocities with all tested protocols. However, there was a high
      risk of making both over- and underestimations (5% to -4%). The lowest risk of
      making an inaccurate prediction was found when a running duration of 8 min for
      each running period was used in combination with an increase in running velocity
      of 0.25 m.s-1, and the lactate measurements were performed in hemolysed capillary
      blood.

PMID- 8157376
TI  - Effect of long-distance running on polymorphonuclear neutrophil phagocytic
      function of the upper airways.
AB  - A high incidence of infections predominantly of the upper and lower respiratory
      tract have been observed for years after strenuous exercise. The mucosal surfaces
      represent a first-line-of-defense for airborne pathogens, but little is known
      about their function during exercise. The purpose of this study was thus to
      assess the influence of long-distance running on polymorphonuclear neutrophils
      (PMNs) phagocytic function of the upper respiratory tract. The number of PMNs
      recovered by nasal lavage (NAL) was determined, and the percentage of
      phagocytizing PMNs and number of phagocytized E. coli per PMN was measured
      utilizing a fluorescence activated cell sorter. A 20 km race resulted in a 2.0
      fold higher count of PMNs in the nasal lavage fluid of 12 male amateur runners
      (aged 34 +/- 11.3 years) immediately after the competition and a 1.6-fold higher
      count 1 day after the race in comparison to the pre-race value. During training
      (7 and 3 days before the race) and after 3 days of recreation (3 days after the
      race) the runners' counts were lower than immediately after the race. The
      percentage of phagocytizing PMNs was significantly reduced during the pre-race
      period, but the reduction was most striking immediately and 1 day after the race
      (48.7 +/- 6.4% and 54.5 +/- 6.2%). The number of bacteria ingested by the
      athletes' phagozytizing PMNs was 3.2 +/- 0.3 E. coli/PMN immediately after the
      race and 5.2 +/- 0.3 1 day after the competition. The findings suggest chronic
      upper airway inflammation and impaired phagocyte function after strenuous
      exercise. This might contribute to the observed high incidence of respiratory
      tract infections among participants in sports.

PMID- 8157377
TI  - Isokinetic evaluation of muscular performance: implications for muscle testing
      and rehabilitation.
AB  - Interfacing of microprocessors with isokinetic dynamometers has enabled the rapid
      quantification of many parameters of muscle function including peak torque, angle
      specific torque, work, power, torque acceleration energy, and various endurance
      indexes, and the measurements with these devices can be made isometrically at
      various angular positions and isokinetically (concentrically or eccentrically)
      with a large scale of angular speeds. Many of these parameters, however, lack
      evidence of validity, reproducibility, and/or clinical relevance. Peak torque has
      been and still is the most properly studied isokinetic strength testing parameter
      and its use can be recommended for research and clinical purposes. Concerning
      testing of muscular endurance, the absolute endurance parameters (for example,
      work performed during the last five repetitions and total work in a 25-repetition
      test with a speed of 240 degrees/s) are the best for use. Many internal and
      external factors in the isokinetic testing procedure can have an undesirable
      effect on the test result. However, through proper education and strict adherence
      to the test instructions, it is possible to successfully control the confounding
      variables. In scientific work, isokinetic devices have greatly expanded the
      possibilities for studying dynamic muscle function. There is also little doubt
      about their usefulness in documenting the progress of muscular rehabilitation. A
      disadvantage of isokinetic devices is that isokinetic movement seldom occurs in
      actual human performance tasks and that the isokinetic training effect is,
      therefore, quite (although not completely) specific to that type of movement. In
      addition, being normally an isolated joint exercise, isokinetic training can
      produce large loads on the involved joints and may, therefore, under certain
      conditions be dangerous for healing tissues.

PMID- 8157378
TI  - Normal values of isokinetic maximum strength, the strength/velocity curve, and
      the angle at peak torque of all degrees of freedom in the shoulder.
AB  - Many acute and chronic complaints in the shoulder joint are due to a reduced
      active stabilization capacity. Procedures to measure isokinetic strength are used
      to objectify the muscle deficits and imbalances of various muscle groups. In this
      study, standard values and reference ranges were determined for peak torque (PT),
      strength/velocity curve, and range of motion (ROM) at peak torque in the shoulder
      in 19 untrained women and 32 men. Differentiation was made by the individual
      degrees of freedom of the shoulder joint and the various types of work
      (concentric, isometric, eccentric). Moreover, the influence of height, body
      weight, and body mass index on isokinetic maximum strength development was
      investigated. It was found that it is necessary to distinguish between the
      various movements and types of work in development of peak torque. A decrease in
      maximum strength is observed in the sequence extension, adduction/flexion,
      abduction/internal rotation, external rotation. The maximum strength of men was
      determined to be higher than that in women. ROM shows a wide fluctuation and does
      not possess high validity. Height, as well as body weight and body mass index
      have only slight influence on the isokinetic maximum strength in the shoulder of
      untrained men and women.

PMID- 8157379
TI  - Force-velocity relations in human skeletal muscle.
AB  - Based on the physiological principles of the muscular force-velocity concept,
      this paper deals with the special problems associated with determining and
      interpreting force-velocity relations of muscles in situ particularly in humans.
      In the strict sense, instead of force-velocity relations merely torque-angular
      velocity relations of a joint can be measured directly under in situ conditions.
      This calls for biomechanical model calculations to obtain force-velocity
      relations of single muscles involved in joint motions. In addition to discussing
      these basic principles, the methodological problems arising in measurements with
      so-called isokinetic dynamometers are also explicitly described. An important
      message of this paper is to sensitize potential users of this method to these
      problems as the isokinetic dynamometry has more or less become standard procedure
      worldwide. The possibility of the characterization of muscle fiber composition
      and the evaluation of power on the basis of human muscle force-velocity relations
      is also discussed. A final section considers the effects of muscle training on
      the torque-angular velocity relations. The contents of this paper can be
      understood as a guide to avoid obtaining conflicting results when measuring human
      torque-velocity relations.

PMID- 8157380
TI  - Reproducibility of isokinetic peak torque and angle at peak torque in the
      shoulder joint.
AB  - Adequate reliability studies of knee flexion and extension are currently
      available for isokinetic measurements, but not for the shoulder joint. For this
      reason, this study examines the variability (%) in the determination of peak
      torque (PT) and the angle at peak torque (AP) in the test-retest procedure.
      Differentiation is made between the various types of work (concentric, isometric,
      eccentric) and the degrees of freedom in the shoulder joint (flexion/extension,
      abduction/adduction, external rotation/internal rotation). The results show a
      variability of PT for concentric measurements of 15.0%-19.0% for all degrees of
      freedom; for flexion/extension and abduction/adduction in isometric and eccentric
      work, the variability is 17.5%-25.3%. External and internal rotation show
      generally greater deviation (29.0%-35.3%), except in concentric work. The angle
      at peak torque can only be reproduced to a limited degree (25.1%-41.1%
      variability). It is concluded that lower reproducibility can be attained for the
      shoulder joint compared to the knee joint, depending on the degree of freedom and
      exercise form tested. It appears meaningful to cite only ranges for the angle at
      peak torque.

PMID- 8157381
TI  - The temporal occurrence of the mean power frequency shift of the electromyogram
      during maximum prolonged dynamic and static working cycles.
AB  - The study investigated the temporal occurrence of the mean power frequency shift
      (MPF) of the EMG during prolonged (dynamic and static) working cycles. Ten
      healthy subjects took part in the experiment. The experimental protocol required
      each subject to first complete 70 maximum isokinetic knee extensions at 90
      degrees s-1). Without any rest, the subject then performed a maximum static knee
      extension with the dynamometer positioned at 45 degrees of flexion until
      subjective exhaustion. This sequence of dynamic and static exercise was repeated
      two more times with a 5-min rest interval preceding each sequence. The EMG signal
      of the rectus femoris was obtained simultaneously with the torque signal (PT)
      from the dynamometer. Dynamic contractions PT and MPF decreased throughout the
      three dynamic periods. Patterns composed of two phases were found; first an
      initial steep decrease during the first 40 contractions followed by a less steep
      decrease. Static contractions PT decreased significantly during the three static
      contractions. Significant (small) decreases in MPF occurred only during the
      second and third static contractions. Since the major part of the MPF shift
      occurred early in the exhaustive performance, it is questioned whether the MPF
      shift detects peripheral fatigue of the type 1 fibers.

PMID- 8157382
TI  - The constant velocity translatoric dynamo ergometer. A new approach to
      investigate neuromuscular, metabolic, and cardiovascular parameters.
AB  - The goal of this study was to investigate with the new dynamo ergometer the
      forces produced within a defined range of motion at a constant velocity during
      concentric translatoric work as well as to investigate fatigue based on
      neuromuscular and metabolic parameters. We examined 11 male sports students with
      the "Motomir" device with the subjects in a sitting position. The test consisted
      of four times 1 min of concentric leg work with 1-min rest phases in between. The
      subjects were asked to do maximum effort push movements with one leg and maximum
      effort pull movements with the other leg. The translatoric form of movement did
      not reveal any significant differences in strength between the left and right
      legs. The strength of the extensors was significantly higher than that of the
      flexors during all exercise stages (p < 0.001). A significant decrease in
      strength was established for extensor muscles and no significant decrease for the
      flexor muscles. The quotient of flexor/extensor was 0.43 +/- 0.07 in the first
      exercise stage and increased in every stage till the fourth. There was a
      correlation (p < 0.001) between the difference in lactate of the first and fourth
      exercise stages and the percentage of force decrease from the 1st to the 4th min.
      The electric activity of the vastus medialis, vastus lateralis, and gastrocnemius
      muscles decreased from the first to the fourth exercise stage. This decrease was
      however not significant. The translatoric constant velocity dynamo ergometer
      allows both diagnosis and training at varying angles and varying speeds while
      avoiding unphysiological maximum loads.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157383
TI  - Experimental results on forced eccentric strength gains.
AB  - It is known that the maximal forces applied during eccentric movements are
      generally higher than the maximal forces applied in concentric or isometric
      contractions. In training theory this phenomenon has so far been regarded as a
      deficit: that means, a subject with high eccentric vs. isometric force values is
      in a bad training state. In the article the hypothesis is tested, whether the
      phenomenon can also be viewed as a gain. To test this hypothesis a new leg press
      station was developed, which creates an overload by means of a motor. With this
      apparatus the subject can be forced into an eccentric movement, even with maximum
      resistance of the subject. The experiments on this apparatus reveal that greater
      end velocities can be reached during an eccentric-concentric movement sequence,
      and that the gain hypothesis can, therefore, be confirmed.

PMID- 8157384
TI  - The cardiocirculatory reaction to isokinetic exercises in dependence on the form
      of exercise and age.
AB  - Although isokinetic training is gaining in importance in prevention and
      rehabilitation, even for older patients, there is hardly any information
      available on the extent of cardiocirculatory stress. This study was aimed,
      therefore, at examining the cardiocirculatory reaction to various isokinetic
      forms of exercise in dependence on age. Sixty-four subjects between 22 and 60
      years of age were assigned to four age groups and the maximum torque measured in
      concentric and eccentric exercises with various angle accelerations. Moreover,
      all subjects underwent 1-min concentric and eccentric endurance stress and an
      isometric test. The cardiocirculatory reaction as reflected in heart rate and
      blood pressure patterns was determined, as well as the plasma catecholamines
      adrenaline and noradrenaline measured. The eccentric maximum torque was
      significantly above the concentric maximum torque; there was a significant
      inverse relationship to age only in the concentric mode of exercise (r = -0.48; p
      < 0.01). The cardiocirculatory reaction in endurance stress and isometry, like
      the behavior of heart rate, blood pressure, and plasma catecholamines, was
      greatest in concentric exercise, although the maximum strength values were lower,
      followed by eccentric exercise and isometry. Exercise values such as those
      attained in maximum ergometric forms of exercise were not reached. It is
      concluded that no special precautionary measures are required in isokinetic forms
      of exercise.

PMID- 8157385
TI  - Metabolic and hemodynamic changes during isokinetic muscle training. A controlled
      clinical trial.
AB  - Twenty-one healthy males aged 20-36 years were examined for hemodynamic and
      metabolic parameters such as heart rate, oxygenation, lactate, blood pressure,
      under isokinetic and ergometric loadings. The healthy volunteers were tested by
      increased loads and constant times with an identical isokinetic and ergometric
      power. The important results are: Heart frequency and blood pressure are higher
      under isokinetic than under ergometric conditions. Oxygenation is equal in both
      tests. The lactate values show for the isokinetic maximal and for the ergometric
      submaximal loadings. The definitive factor for this variation is the relation
      between force and velocity. The higher tension of the muscles and the higher
      activity of the fast-twitch fibers seem to be responsible for the increasing of
      sympathicotonia. The clinical impact of this controlled study is: 1. Isokinetic
      testing might be dangerous for patients with cardiac diseases or circulatory
      disturbances. 2. Isokinetic training programs have to pay attention to joint and
      internal diseases at the same level. 3. During the first isokinetic test all
      precautions for a possible emergency case have to be taken.

PMID- 8157386
TI  - Contraction patterns during isokinetic eccentric and concentric contractions
      after anterior cruciate ligament injury.
AB  - Muscular fatigue was investigated in m. rectus femoris, m. vastus lateralis and
      medialis of 15 patients after an anterior cruciate ligament injury. Using a Lido
      active (isokinetic) dynamometer, combined eccentric and concentric contractions
      were carried out at intermediate contractile velocity speeds (150 degrees, 240
      degrees/s). In addition, concentric contractions were also performed at fast
      angular velocities (300 degrees, 400 degrees/s). The results indicated that
      fatigue was significantly greater for the intermediate speeds. Given one angular
      velocity, the average eccentric force decline was more pronounced than the
      concentric one. At all velocities the relative decrease of peak torque (PT) was
      smaller than for contractional work (CW).

PMID- 8157388
TI  - Nehushtan: the globality of cutaneous medicine.

PMID- 8157387
TI  - Isokinetic force-velocity curves in patients following implantation of an
      individual total hip prosthesis.
AB  - There are only a few studies which could support conclusions concerning the
      strength of the muscles surrounding the hip joint and especially concerning the
      strength relationships following implantation of endoprostheses. The aim of this
      study was to examine the post-operative course of strength deficits in this
      musculature compared to clinical parameters. Fifty-eight patients between 30 and
      67 years of age, in whom individual total hip prostheses were implanted, were
      clinically examined prior, 9 weeks and 6 months after surgery. Moreover, the
      maximum isometric strengths of abductors, flexors, and rotator muscles as well as
      maximum isokinetic strengths of the extensors and flexor musculature at 60
      degrees/s and 120 degrees/s were measured. The flexor and extensor musculature
      already showed a clear increase in maximum strength after 9 weeks and 6 months.
      By contrast, the isometric strengths of the rotators increased only slightly, the
      abductor strength decreased after 9 weeks to below the preoperative baseline
      level and attained this level again only after 6 months. The clinical parameters
      Trendelenburg sign, limping, and walking capacity were clearly improved after 6
      months, but no correlation to the abductor strength could be demonstrated. It is
      concluded that limp-free gait can be attained even without maximum strength
      increase in the abductors, which are important for fluid gait, at least for short
      distances. The importance of regular training of the rotator and abductor
      musculature in coxarthrosis is emphasized to delay limitation of movement and
      decreased strength in the sense of a capsule pattern.

PMID- 8157389
TI  - Cryosurgery: a useful tool in the treatment of selected infectious diseases.

PMID- 8157390
TI  - Papulonecrotic tuberculid secondary to disseminated Mycobacterium avium complex.
AB  - BACKGROUND: Papulonecrotic tuberculid is a rarely reported cutaneous reaction to
      the mycobacterium bacillus. It is most often encountered in association with
      tuberculosis. The clinical and histologic picture of the entity is a distinctive
      one, but the etiology of the disease process is uncertain. Therapy directed
      against the causative organism is dramatically successful. METHODS: A 35-year-old
      white man with AIDS was referred to the Dermatology clinic for evaluation of a
      widespread skin eruption. The skin lesions were biopsied for histopathology and
      culture. From the cutaneous cultures Mycobacterium avium complex (MAC) organisms
      were grown. RESULTS: We report the first case of papulonecrotic tuberculid
      manifestation in an AIDS patient with disseminated MAC. Unusual features seen in
      this case include the predominance of pruritic eschars rather than asymptomatic
      papules and the confirmation by special stains of mycobacterium organisms within
      the skin biopsy. Papulonecrotic tuberculid has not been previously associated
      with either MAC or AIDS. CONCLUSIONS: Papulonecrotic tuberculid should be a
      diagnostic consideration in immunocompromised patients with MAC whose clinical
      and histologic features are compatible with this rare entity.

PMID- 8157391
TI  - Photography without film: low-cost digital cameras come of age in dermatology.
AB  - BACKGROUND: Photography is integral to the practice of dermatology. Digital
      imaging techniques have only recently been used to assess cutaneous disorders.
      Previously reported imaging systems have been both expensive and cumbersome.
      Consequently, they have failed to gain wide-spread acceptance. METHODS: We
      describe our experience using an inexpensive digital camera. Photographs taken
      with this portable digital camera (FotoMan) compare favorably to those obtained
      with conventional 35 mm cameras. RESULTS: This inexpensive digital camera
      provides photographs of acceptable quality for a variety of dermatologic
      applications. Images created with this system are available within minutes and
      are less expensive than traditional photographs. CONCLUSIONS: Digital imaging is
      a new and exciting development. The digital camera described is simple to operate
      and provides a useful alternative or adjunct to conventional photography.

PMID- 8157392
TI  - An outbreak of phytophotodermatitis due to celery.
AB  - BACKGROUND: Celery is known to contain psoralens, a group of substances that
      cause a toxic dermal reaction on exposure to ultraviolet A rays (UVA). An
      outbreak of phytophotodermatitis amongst 11 workers in a celery harvest in
      southern Israel is reported. METHODS: Analysis of the trigger factors was carried
      out. The patients were questioned regarding their working conditions. Samples of
      the celery that the workers had been harvesting were analyzed for levels of total
      psoralens by means of high performance liquid chromatography (HPLC). Levels of
      UVA were measured. RESULTS: It was found that the celery harvested in the south
      of the country contained 84 micrograms/g fresh weight (f.wt.) total psoralens as
      compared to 35 micrograms/g f.wt. in celery harvested in the north of the country
      at the same time. The following year the celery harvested in the south contained
      only 26 micrograms/g f.wt. total psoralens. Other risk factors noted were that
      the subjects had fair skin, wore no protective clothing, and worked with moist
      hands. In addition, the days were clear and sunny thus ensuring maximal UV
      radiation for that time of the year. CONCLUSIONS: Multiple factors contributed to
      the outbreak of phytophotodermatitis. A late harvest in the south of the country
      is incriminated as the cause of the unusually high levels of psoralens in the
      celery of that year.

PMID- 8157393
TI  - Hyaluronic acid in cutaneous intrinsic aging.
AB  - BACKGROUND: In elderly individuals all components of the skin and subcutaneous
      tissue undergo histologic and ultrastructural changes. The turgidity of the
      dermis appears decreased, presumably due to altered patterns and levels of
      glycosaminoglycans (GAGS), especially hyaluronic acid and dermatan sulfate that
      are the most common. A linear, age-related decrease in the content of GAGS
      (mainly hyaluronic acid) has been hypothesized in human aged skin. METHODS: We
      used the cationic dye Alcain Blue to selectively stain hyaluronic acid within the
      dermis in old and young subjects to compare ultrastructurally its topography and
      variations with age. RESULTS: We demonstrated a progressive reduction in the
      number of electron-dense granules of hyaluronic acid and of their filaments until
      they were completely absent in subjects aged 60. CONCLUSIONS: We propose that the
      variations of the levels of hyaluronic acid in the dermis in aging could account
      for some of the most striking alterations of the aged skin, including decreased
      turgidity, less support for microvessels, wrinkling, and altered elasticity.

PMID- 8157394
TI  - The relationship between facial wrinkling and airflow obstruction.
AB  - BACKGROUND: Similar smoking-related changes in the collagen and elastin could
      play a role in the pathogenesis of both skin wrinkling and chronic airflow
      obstruction. The hypothesis was tested by analyzing whether increased facial
      wrinkling, especially in smokers, is associated with the presence of airflow
      obstruction. METHODS: An age-stratified randomized sample of the general
      population comprising 6034 men and 7152 women between 30 and 80 years of age was
      analyzed. The recording of wrinkling in the crow's foot area of the right eye was
      performed according to an earlier described severity score. As an index of
      airflow obstruction, we used the ratio between forced expiratory volume in 1 s
      and forced vital capacity in percent (FEV1/FVC%). RESULTS: Multiple regression
      analysis comprising current and previous smokers showed that, after controlling
      for age, subjects with highest wrinkle scores had on average FEV1/FVC% that was
      1.2-1.9% lower than in subjects with lower wrinkle scores. No association between
      facial wrinkling and airflow obstruction was observed among lifetime nonsmokers.
      CONCLUSIONS: Increased facial wrinkling is independent of age when associated
      with airflow obstruction in smokers, but not in never-smokers. The magnitude of
      this association, however, is small.

PMID- 8157395
TI  - Myiasis due to Cordylobia anthropophaga (Tumbu-fly).

PMID- 8157397
TI  - Behcet's disease: aggressive pulmonary involvement.

PMID- 8157396
TI  - Acute cutaneous toxoplasmosis presenting as erythroderma.

PMID- 8157398
TI  - Coexistent lichen sclerosus et atrophicus and atrophoderma of Pasini and Pierini.

PMID- 8157399
TI  - Coexistence of pseudocyst of the auricle and preauricular fistula.

PMID- 8157400
TI  - Facial seborrheic dermatitis treated with fluconazole 2% shampoo.

PMID- 8157401
TI  - Effects of softened and unsoftened fabrics on infant skin.
AB  - BACKGROUND: The effects of softened and unsoftened fabrics on the skin of infants
      of 1-12 months of age were evaluated under real life conditions of skin contact
      with fabrics. METHODS: During 4 weeks, 24 infants wore cotton fabrics washed with
      a granular detergent on one side of their lower back, and on the other side,
      cotton fabrics washed with the same detergent and softened with a liquid fabric
      softener. Skin effects were evaluated by visual grading for redness, dryness, and
      smoothness, by skin stripping and measuring of Chroma C* (squamometry), by
      measurements of elasticity and bioelastic ratio, and by instrumental measurements
      of skin parameters (pH, capacitance, transepidermal water loss (TEWL), and
      erythema by colorimetry). RESULTS: No deleterious effects were observed in any
      infant. A decrease in squamometry (Chroma C*) and an increase in capacitance were
      detected in skin exposed to softened fabrics relative to unsoftened ones. Values
      of pH tended to be higher in the sites treated with softened versus unsoftened
      fabrics (pH 6.06 and 5.87, respectively, at end of study). All other parameters
      showed no significant differences in the two treatment groups. CONCLUSIONS:
      Neither softened nor unsoftened fabrics produced any adverse effects on the skin
      of infants after continuous wearing during 29 days. A slight beneficial effect on
      the infants' skin was observed with softened relative to unsoftened fabrics.
      Methods measuring the structure and function of the stratum corneum were more
      sensitive discriminators of the effects of fabrics on the skin than traditional
      methods of visual clinical evaluation.

PMID- 8157402
TI  - Hansen's disease patients: responses to stigma and segregation in Kumamoto,
      Japan.

PMID- 8157403
TI  - Actinic prurigo.

PMID- 8157404
TI  - Cutaneous myiasis: a simple and effective technique for extraction of Dermatobia
      hominis larvae.

PMID- 8157405
TI  - Vesicular scabies.

PMID- 8157406
TI  - Eccrine sweat gland disorders: Part I--Neoplasms.

PMID- 8157407
TI  - Cyclosporine in dermatology: pharmacology and clinical use.

PMID- 8157408
TI  - Cutaneous tuberculosis: the evolving scenario.

PMID- 8157409
TI  - Magnetic resonance imaging of airway obstruction resulting from vascular
      anomalies.
AB  - Accurate diagnosis is important in the evaluation of airway disorders of infants
      and children. Today, multiple imaging techniques are available to evaluate the
      pediatric airway. We performed magnetic resonance (MR) imaging of the airway in
      16 infants and children with symptoms of airway obstruction. Fourteen of 16
      patients symptoms were related to compression of the airway by vascular
      structure. MR imaging was useful in the diagnosis and management of these
      patients without the need for more invasive procedures.

PMID- 8157410
TI  - Additional conductive hearing loss in children from a school for the deaf in
      Malaysia.
AB  - A total of 165 children from a school for the deaf in Malaysia were screened to
      find out the prevalence of additional conductive hearing loss. Otological
      examination, tympanometry and pure tone audiometry were performed in all these
      children. Fifty-one children (30.9%) had additional conductive hearing loss.
      Middle ear disorders were present in 15 children (9.09%). The deaf children
      seldom complain about the change in their hearing sensitivity, so there is a need
      for regular otological examination in deaf children to detect the additional
      conductive hearing loss.

PMID- 8157411
TI  - Compliance with prophylactic antibiotics for otitis media in a New York City
      clinic.
AB  - Although previous efficacy studies have reported high compliance rates among
      children treated by private physicians with prophylactic antibiotics for
      prevention of otitis media, compliance rates in a lower socioeconomic, urban
      clinic population have not been well described. Eighty children who were placed
      on daily low dose antibiotics in the Pediatric Otolaryngology Clinic at Bellevue
      Hospital were prospectively followed in order to estimate compliance in this
      population. Compliance was estimated by the parent's stated word alone. Of the 77
      patients with records adequate for analysis, only 36 (46.8%) families claimed
      compliance, 18 (23.4%) admitted non-compliance, and 23 (29.9%) did not reliably
      return for follow-up clinic visits. Statistical analysis revealed that no single
      characteristic of the patient population or the treatment regimen strongly
      influenced compliance. The factors examined included: the child's age, sex, race
      and otologic diagnosis, the type of prophylaxis prescribed, the parent's ability
      to speak English, national origin, consistency of follow-up, and method of
      payment. Based on these results, less than half of the children attending an
      inner city clinic compiled with maintenance medication. The clinician should
      consider alternate treatment modalities, such as the insertion of middle ear
      ventilation tubes, if poor compliance with prolonged antibiotic treatment is
      suspected.

PMID- 8157412
TI  - Pathological changes of the lateral nasal wall in patients with cystic fibrosis
      (mucoviscidosis).
AB  - In a prospective clinical study, 84 patients aged 3 months to 34 years (mean age:
      12 years; 53 males and 31 females), with cystic fibrosis systematically underwent
      an ENT examination, including rigid endoscopy of the anterior nasal cavity and
      lateral nasal wall. In 28 cases, CT-scan of the sinuses was performed.
      Mucopyosinusitis of the maxillary sinus with medial projection of the inter-naso
      sinusal wall was present in 10 children (12%, mean age: 4 years; range: 3 months
      to 8 years). Nasal polyposis was present in 37 patients (45%) from the age of 5
      years on (mean age: 15 years). Nasal obstruction was the main complaint when the
      condition was severe. The routine use of the endoscope makes it possible to
      diagnose early pathological changes of the lateral nasal wall. Local treatment
      could then help slow down progress evolution toward a more massive involvement.

PMID- 8157413
TI  - Comparison of bacterial culture results in bronchoalveolar lavage and nasal
      lavage fluid in children with pulmonary infection.
AB  - In this prospective study, bronchoalveolar lavages (BAL) as well as nasal lavages
      (NL) were performed in 25 consecutive pediatric patients with pulmonary
      infections. It aimed to study the relevance of bacterial culture results from
      nasal lavage fluid as compared with bronchoalveolar lavage fluid in children with
      pulmonary infection. Purulent nasal secretions were observed in 9 out of 10
      children presenting with acute unilateral pneumonia within 1-2 days and who had
      not been treated with antibiotics (Group 1), and in 10 out of 15 children who had
      been ill for about 1-3 weeks and had not improved, even though antibiotic therapy
      had been instituted (Group 2). Potential bacterial pathogens were isolated from
      the NL of almost all the patients (24/25). In 6 of the 10 patients in Group 1,
      BAL cultures were positive; the pathogens present in BAL fluid were also found in
      the nose in all cases. In 8 of the 15 patients in Group 2, BAL cultures were
      positive; the pathogens present in BAL fluid were also found in the nose in 7
      cases. The total number of bacterial isolates recovered from NL fluid was higher
      (n = 32) than that from the BAL fluid of the involved lung (n = 17). Ten patients
      with a positive NL fluid culture had negative BAL culture. This shows that nasal
      bacteriological findings were rather poor predictors of the actual
      bronchoalveolar bacteriology. It is, however, logically accepted that bacterial
      pathogens from the upper respiratory tract spread to the lower respiratory tract,
      but that not all bacteria sited in the nose will eventually infect the lung.

PMID- 8157414
TI  - Coagulation profile as a predictor for post-tonsillectomy and adenoidectomy (T +
      A) hemorrhage.
AB  - The risk of hemorrhage after tonsillectomy and adenoidectomy (T + A) was studied
      in 1061 children. Twenty-seven (2.5%) had at least one abnormality on a
      preoperative coagulation profile consisting of a prothrombin time (PT), partial
      thromboplastin time (PTT), bleeding time (BT) and platelet count (PC). Of these
      27 who had an initially abnormal test (PTT or bleeding times only), 8 had
      diagnosed coagulopathies by hematology evaluation (Group A), and 17 had repeat
      tests which returned to normal (Group B). Two borderline tests (PTT) were not
      repeated (Group C). Sixty-four patients (6.0%) bled after T + A. Six of these
      (9.3%) had an initially abnormal coagulation profile--one in Group A (12.5%),
      four in Group B (23.5%) and 1 in Group C (50%). This is in contrast to the bleed
      rate of 5.7% for the 1034 children with normal coagulation profiles. Although it
      is not surprising that 6 (22.2%) children with an initially abnormal coagulation
      profile bled, of note is that 4 of them had an initially abnormal coagulation
      profile which upon repeat testing returned to normal. However, none of these four
      bleeders required active intervention for control. Coagulopathies were newly
      diagnosed in 7 (0.57% of total group; 25.9% of 27 with abnormal laboratory
      values). One additional child had a known intrinsic platelet dysfunction prior to
      surgery. Only one child was newly identified by a positive family history for
      abnormal bleeding. These results suggest that new hematologic disorders were
      diagnosed infrequently. An initially abnormal coagulation profile may identify
      those more likely to bleed after surgery (22.6% vs. 5.5%). A coagulation profile
      which includes a PTT and BT may be a valuable screening tool for children
      undergoing T + A.

PMID- 8157415
TI  - Audiologic and impedancemetric findings within thalassaemic patients.
AB  - The objective of this study is to investigate hearing losses in thalassaemic
      patients. This study was conducted on 34 thalassemic patients of which 27 of them
      had thalassaemia major and the remaining 7 had thalassaemia intermedia. Six
      (11.11%) of the 54 ears with thalassaemia major were found to have normal
      hearing. Thirty-two ears (59.26%) had conductive hearing loss, 8 ears (14.81%)
      had mixed type of hearing loss. Moreover, in this group, there was no ear which
      had pure sensorineural hearing loss. Of the majority of patients having
      thalassaemia major and thalassaemia intermedia, an air bone gap was found even
      though there was no negative pressure in the middle ear. In these patients a high
      degree of static compliance and normal shaped, stiff amplitude, normal pressure
      tympanograms were observed. Moreover, in most of these patients acoustic reflexes
      were not obtained. These findings are rather interesting since they show the
      pathological changes which may cause stiffness in the middle ear sound
      transmission system.

PMID- 8157417
TI  - Long-term results of neonates with nasal deviation: a prospective study over 12
      years.
AB  - In the literature of the past 100 years only a few cases with documented long
      term healing of intrauterinely acquired nasal deviation could be found. Therefore
      we prospectively investigated 3425 children who were born between 1980 and 1981
      in the Obstetric Department of the University Hospital of Ulm. In this group 29
      neonates (0.86%) showed a deviation of the bony and cartilaginous nose related to
      intrauterine injury. After a period of 11-12 years we could reexamine 14 children
      by otorhinolaryngological examination, photographic documentation of the face and
      acoustic rhinometry. After 11-12 years nine children presented a straight nose
      and five children (36%) showed a deviation of the nasal pyramid to the same side
      as found at birth--markedly in two girls and slightly in three girls.
      Unexpectedly high was the rate of malocclusions, namely in 13 out of 14 children.

PMID- 8157416
TI  - Silent aspiration prominent in children with dysphagia.
AB  - Children with neurologically-based dysphagia are at high risk for silent
      aspiration. Aspiration can lead to complications such as acute pneumonia and
      chronic lung disease. Thorough evaluation of the oral, pharyngeal, and esophageal
      phases of swallowing is crucial for patients with dysphagia. The
      videofluoroscopic modified barium swallow study (MBS) is the procedure of choice
      for children to delineate the pharyngeal and upper esophageal phases of the
      swallow that can only be inferred by bedside clinical assessment. This study
      describes attributes of aspiration and pharyngeal motility in a large sample of
      infants and children assessed with MBS. Aspiration was observed in 48 (26%) of
      186 children, primarily on liquid before or during swallows. Aspiration was trace
      (less than 10% of a bolus) and silent in 94%. Relationships to clinical history
      and implications for management are discussed. Given the lack of objective
      clinical information to identify children at risk for aspiration, MBS should be
      considered in all children with severe dysphagia to rule out or confirm
      aspiration.

PMID- 8157418
TI  - Airway compromise secondary to vascular compression in a neonate.
AB  - Respiratory distress in the neonate may be due to extrinsic tracheobronchial
      compression. We recently observed a neonate with left mainstem bronchus
      obstruction resulting in respiratory distress and mediastinal shift. Initial
      management required intubation and positive pressure ventilation. Bronchoscopic
      evaluation demonstrated compression of the proximal left main bronchus. The
      distal bronchus appeared normal. Bronchography, echocardiography and an MRI of
      the chest confirmed proximal compression of the bronchus and suggested that the
      cause was an aneurysmal left pulmonary artery and patent ductus arteriosus. With
      medical therapy there was resolution of the bronchial compression. Re-evaluation
      by bronchoscopy and echocardiography revealed a normal left main stem bronchus, a
      normal left pulmonary artery and a closed ductus arteriosus. This clinical
      scenario suggests that transient pulmonary hypertension may result in significant
      airway compression due to the proximity of the left main stem bronchus to the
      left pulmonary artery.

PMID- 8157419
TI  - Nasal pyriform aperture stenosis and the holoprosencephaly spectrum.
AB  - Recent reports have described congenital nasal pyriform aperture stenosis, but do
      not address its etiology in detail. We describe a child with nasal pyriform
      aperture stenosis, submucus cleft palate, and hypoplastic maxillary sinuses.
      Chromosome analysis revealed a ring chromosome 18. Awareness of the association
      of midline facial defects with midline brain defects allowed us to predict that
      features of the holoprosencephaly sequence would be found. Subsequent evaluation
      revealed growth hormone deficit. Eventually the child manifested a single central
      incisor. We review the association between midline facial defects and
      holoprosencephaly to remind the otolaryngologist of the need to look at the whole
      patient as he treats specific upper airway problems.

PMID- 8157420
TI  - Reconstruction of the pediatric airway with an open stented tracheotomy tube.
AB  - Reconstructive techniques for the stenotic pediatric airway have greatly enhanced
      the otolaryngologists ability to decannulate the tracheotomy-dependent child.
      Stents have played an important role in this process by both maintaining the
      reconstructed lumen and acting as a scaffold. However, decannulation is often not
      achieved after the first surgical intervention with some patients requiring two,
      three or more procedures. In an effort to improve upon the design of today's
      stents, an open stented tracheotomy tube was evaluated at our institution. This
      stent is designed to provide advantages of immediate postoperative voice and
      nutrition, and ease of evaluation, as well as to provide for safe and adequate
      healing. Four patients underwent laryngotracheal reconstruction with this stent
      over a 10-month period. All patients could vocalize and eat immediately
      postoperatively but recalcitrant granulation tissue and restenosis has prevented
      decannulation in three of the cases. The experience with this stent exemplifies
      the persistent difficulties of stent use in pediatric airway reconstruction. It
      also points out that progress is still needed in current reconstructive
      techniques as well as in the development of new techniques.

PMID- 8157421
TI  - Otalgia in infants and children--a manifestation of gastroesophageal reflux.
AB  - To investigate if there is a relationship between gastroesophageal reflux and ear
      pain in the pediatric age group, a series of children presenting with this
      picture were analyzed. Infants and children are often seen in an emergency room
      setting because of fretfulness, irritability, and pulling on the ears. A
      diagnosis of otitis media is usually made, but in some cases the diagnosis may be
      referred otalgia secondary to gastroesophageal reflux. Six children who presented
      with the above picture were seen by one of the authors (W.S.G.) the following
      morning and noted to have a normal ear exam. These children were studied for
      gastroesophageal reflux by esophageal pH monitoring and in some cases
      esophagoscopy with biopsy. All children exhibited gastroesophageal reflux and an
      anti-reflux regimen eliminated the pattern of 'recurring otitis media'. This
      paper will review the mechanism of referred otalgia along with data supporting
      the concept of GE reflux as a cause of otalgia in infants and children.

PMID- 8157422
TI  - Congenital tumors of the dorsum of the tongue.
AB  - Five children presented with masses on the dorsum of the tongue. Excisional
      biopsies were performed. Histologic examination showed the masses to be
      lipoblastomas, hamartomas and one heterotopic neuroglial tissue. A description of
      the clinical presentation and pathological nature of these lesions is presented.

PMID- 8157423
TI  - Progressive sensorineural hearing loss (SNHL) and peripheral neuropathy: a case
      report.
AB  - Sensorineural hearing loss (SNHL) is infrequently associated with peripheral
      neuropathy. When co-existent with peripheral neuropathy, it tends to present in
      the early adult years, is slowly progressive and is accompanied by optic atrophy
      or bowel abnormalities. The following case presents an unusual patient with
      severe and rapidly progressive SNHL and peripheral neuropathy.

PMID- 8157424
TI  - Massive cystic heterotopic brain tissue.
AB  - The differential diagnosis of large cystic masses in the newborn should include
      heterotopic brain tissue. This lesion is attributed to early displacement of
      pluripotential cells and cyst formation may result from cerebrospinal fluid
      production by choroid plexus-like structures. Treatment consists of surgical
      excision.

PMID- 8157425
TI  - Congenital lobar emphysema: a case with bronchial septum.
AB  - Congenital lobar emphysema has been described under various designations.
      Although the etiology is not clear, some form of bronchial obstruction has been
      documented in about 50% of the patients. A rare case of congenital lobar
      emphysema with a membranous septum in the left main bronchus is described.
      Although prompt lobectomy has been the treatment of choice in most cases, this
      case demonstrates the importance of early bronchoscopy to exclude treatable intra
      luminal abnormalities.

PMID- 8157426
TI  - Embryonal rhabdomyosarcoma arising in the buccal mucosa: a case report with
      immunohistochemical and electronmicroscopic findings.
AB  - Rhabdomyosarcoma is one of the most common soft-tissue neoplasms in children. We
      report a case of a 9-year-old female with embryonal rhabdomyosarcoma arising in
      the buccal region with immunohistochemical and electronmicroscopic findings.
      Under a light microscope, it was observed that the tumor was composed of small
      round or spindle-shaped cells with pleomorphic and hyperchromatic nuclei. They
      were immunoreactive for actin, myoglobin and desmin. With an electron microscope,
      it was found that most tumor cells contained filamentous structures and free
      ribosomes. Some of them showed typical myofilaments, M-bands and Z-lines. These
      findings were specific evidence of rhabdomyosarcoma. Twenty courses of VAC
      (vincristine, D-actinomycin and cyclophosphamide) chemotherapy were administered,
      followed by surgical resection of the tumor.

PMID- 8157427
TI  - Recording auditory brainstem responses from infants.
AB  - Auditory brainstem responses (ABRs) can be reliably recorded from infants in the
      first few months of life. Since they are normally recognizable down to
      intensities that are 30 dB above normal hearing thresholds, ABRs elicited by
      clicks are useful in screening for hearing-impairment in infancy. The ABRs can
      also provide further diagnostic information about the hearing losses that are
      detected by screening: the threshold for the response represents a reasonable
      estimate of the severity of the hearing loss; bone-conduction studies can assess
      the extent of a conductive loss; and frequency-specific techniques can evaluate
      hearing thresholds at different frequencies. At present, ABRs are mainly used for
      screening infants who have been treated in neonatal intensive care units. Because
      the majority of infants with hearing impairment are not seen in these units, it
      might be worthwhile to use ABRs in a more widespread screening program.

PMID- 8157428
TI  - FLAIR Concerted Action No 10 status papers. Introduction, conclusions and
      recommendations.

PMID- 8157429
TI  - Vitamin A.

PMID- 8157430
TI  - Vitamin D.

PMID- 8157431
TI  - Vitamin E.

PMID- 8157432
TI  - Carotenoids.

PMID- 8157434
TI  - Riboflavin.

PMID- 8157433
TI  - Thiamin.

PMID- 8157435
TI  - Vitamin B6.

PMID- 8157436
TI  - Vitamin B12.

PMID- 8157437
TI  - Vitamin C.

PMID- 8157438
TI  - Iron.

PMID- 8157439
TI  - Zinc.

PMID- 8157440
TI  - Copper.
AB  - Static and functional indices used for the assessment of copper status in humans
      are discussed in this review. Variations, advantages and disadvantages of the
      different indices are reported. Good indices of copper status remain to be found.

PMID- 8157441
TI  - Selenium.

PMID- 8157442
TI  - Introduction: vaccine technologies and public health. Why a critical review now?
AB  - Since Jenner's time, there have always been enthusiasts and skeptics about the
      role of vaccines in the prevention of disease. This introduction explains why, at
      this time, it is crucial to assess the historical role vaccines have played in
      limiting damage caused by infectious diseases, the role they can play in the
      future, and the technologies that are best suited to achieving optimal gains for
      public health and development worldwide.

PMID- 8157443
TI  - Adjuvants and immune enhancement.
AB  - Adjuvants increase cell-mediated and humoral immune responses to specific
      antigens. Used with recombinant viral antigens, they can elicit the production of
      T lymphocytes that lyse target cells, expressing the antigen in a genetically
      restricted fashion. Adjuvants can augment the production of interferon-gamma,
      thereby favoring the production of protective antibody isotopes, such as
      immunoglobulin G2a in the mouse. Modern adjuvants display the efficacy of
      Freund's complete adjuvant without its side effects. One such adjuvant is Syntex
      adjuvant formulation, a synthetic analogue of muramyl dipeptide in a
      microfluidized squalane/squalene-in-water emulsion. Monophosphoryl lipid A in a
      similar lipid emulsion is also effective. Immune-stimulating complexes of saponin
      and antigens elicit potent cell-mediated and humoral responses. A purified
      saponin component has adjuvant activity with reduced side effects; liposomes also
      can have adjuvant activity. Administering antigens in adjuvants can overcome low
      responsiveness in very young and old experimental animals and in those that are
      genetically low responders. Adjuvants are likely components of a new generation
      of recombinant and subunit vaccines.

PMID- 8157444
TI  - Novel approaches to controlled-release antigen delivery.
AB  - Two strategies for vaccine-delivery systems, both relying on concepts of
      controlled-release technology, are described in this review. The first strategy
      involves using biodegradable polymer microspheres for parenteral and oral
      delivery of antigens. The other strategy combines two technologies, the
      encapsulation of antigen within liposomes and liposome encapsulation in
      hydrogels, to protect them from a rapid degradation in vivo. Both strategies have
      shown promise in terms of increasing the immunogenicity of poorly immunogenic
      peptides and protein vaccines. The microencapsulation process, antigen stability,
      mechanism of antigen release, and optimal release kinetics for vaccine delivery
      are reviewed, and the strengths and weaknesses of each approach are discussed.

PMID- 8157445
TI  - Live attenuated vaccine vectors.
AB  - Several different live attenuated vaccine vectors currently are under
      development. These vaccines are composed of living viruses or bacteria that are
      innocuous to the host but can replicate in host tissues and induce immune
      responses. The genes encoding foreign antigens can be inserted into these vectors
      to produce multivalent vaccines that promise to induce immunity to more than one
      target disease after the administration of a single dose of vaccine.

PMID- 8157446
TI  - The effectiveness of means of controlling communicable diseases.
AB  - Most communicable diseases are caused by infectious agents that are not visible
      to the naked eye, which led earlier societies to believe in miasmas and control
      by quarantine. Although microscopes revealed the agents in the eighteenth
      century, they were not associated with disease syndromes until the late
      nineteenth century. Today, vaccines are the most cost-effective means of control.

PMID- 8157447
TI  - Maternal immunization to prevent infectious diseases in the neonate or infant.
AB  - The approach of providing passive protection to young infants by immunizing
      pregnant women can bypass the problems of immunological immaturity in the
      neonate, avoid or delay active immunization of the infant in the first year of
      life, and prevent transmission of an infection from the mother to the neonate.
      Optimal vaccines for this approach should induce high immunoglobulin G antibody
      titers that quickly reach their maximum level after immunization and persist at
      protective levels for several years, thus providing passive protection in
      subsequent pregnancies. Specific applications of this approach include the
      worldwide practice of maternal immunization with tetanus toxoid vaccine and
      ongoing studies of maternal immunization to prevent Haemophilus influenzae type
      b, group B streptococcal, pneumococcal, meningococcal, and human immunodeficiency
      virus infection in the infant. Addressing the cultural, sociological, and legal
      aspects of maternal immunization will be required to ensure the success of this
      approach.

PMID- 8157448
TI  - Immunization of the neonate.
AB  - The generation of diversity of T and B cells begins early in gestation. Selective
      restrictions in expression of V genes occur in fetal life, but insufficient
      clonal diversity is not likely to limit newborn immune capabilities. The
      functional immaturity of neonatal T and B cells is beginning to be defined.
      Virgin T cells lack the capacity to produce diverse lymphokines, whereas neonatal
      B cells are less responsive to the lymphokines that promote terminal
      differentiation to plasma cells.

PMID- 8157449
TI  - Glycoconjugate vaccines. What next?
AB  - The principle that infants can be protected from invasive diseases caused by
      encapsulated organisms has been proved with the introduction of Haemophilus
      influenzae type b conjugate vaccines. The use of glycoconjugates to implement
      some of the goals of the Children's Vaccine Initiative requires a clear
      delineation of the chemical and immunological specifications for optimal
      vaccines.

PMID- 8157450
TI  - The thermostability of vaccines. Technologies for improving the thermostability
      of the oral poliovirus vaccine.
AB  - Technologies that promise to enhance the stability of vaccines are likely to be
      determined by the product-specific physical structure and biological functions of
      the specific vaccine immunogens. Research may define the extent to which the
      stability of oral poliovirus vaccine may be improved by the addition of certain
      antiviral components that bind to the poliovirus capsid or by the application of
      novel drying technologies.

PMID- 8157451
TI  - Combination vaccines.
AB  - The availability of new vaccines for pediatric use provides an unprecedented
      opportunity to prevent serious infectious diseases and their associated morbidity
      and mortality. However, each new product entails the need for additional
      injections that could become so numerous as to discourage the administration of
      new vaccines. This challenge can be overcome by mixing individual vaccines before
      delivery such that multiple vaccines are administered as single combination
      vaccines. Technical, clinical, manufacturing, regulatory and marketing issues
      relative to combination vaccines in general are the major challenges for ongoing
      and future development.

PMID- 8157452
TI  - A new technologic synthesis. The Children's Vaccine Initiative.

PMID- 8157453
TI  - Report from the Center for Technology Assessment and Quality Improvement in
      Health Care of the Veneto Region (Italy). Establishment of a Regional Center for
      Technology Assessment and Quality Improvement in Health Care.

PMID- 8157454
TI  - Reports from the Conseil d'evaluation des technologies de la sante du Quebec.

PMID- 8157455
TI  - Report from the French Agence Nationale pour le Developpement de l'Evaluation
      Medicale (ANDEM). Evaluation of the application of nocturnal nasal continuous
      positive airway pressure in the treatment of obstructive sleep apnea.

PMID- 8157456
TI  - Report from the U.K. King's Fund Centre. Criteria for change: the history and
      impact of consensus development conferences in the United Kingdom.

PMID- 8157457
TI  - The contribution of immunization to economic development.
AB  - Immunization received intensive support during the 1980s in light of its
      demonstrable value, relatively low cost, and established infrastructure. The goal
      of universal childhood immunization was achieved in 1990 on the basis of a
      strategy of expanding coverage, technological improvements, and social
      mobilization. Although its impact is difficult to quantify precisely, the
      Expanded Programme on Immunization (EPI) has had significant positive effects on
      national and household economies as a result of the reduction of morbidity and
      mortality. It also has contributed to the development of the managerial and
      operational capacity of health systems and to the generation of widespread social
      and political support for health actions through a variety of different
      mechanisms. Priorities for the next decade include attention to policies to
      ensure the maintenance of high levels of coverage, continued technical
      development, and further strengthening of EPI planning and management.

PMID- 8157458
TI  - The role of vaccine research and development in the scientific development of
      middle-income countries.
AB  - As a new global strategy for improving public health, the Children's Vaccine
      Initiative implicitly raises, once again, the question of the role of science in
      developing countries. If there are to be new and improved vaccines, better
      delivery systems, and simplified immunization schedules, there must be
      substantial analysis, laboratory activity, and fieldwork to ensure that the new
      products are ready for effective use. In the context of these requirements, this
      paper reviews the possibilities for vaccine research and development in middle
      income countries and the benefits in terms of fostering socioeconomic development
      through integrated scientific health research.

PMID- 8157459
TI  - The global capacity for manufacturing vaccines. Prospects for competition and
      collaboration among producers in the next decade.
AB  - Can the world respond to the demands of the Children's Vaccine Initiative (CVI)
      to produce large quantities of affordable vaccines that have never been
      manufactured previously? Vaccines for the world's birth cohort of 150 million
      will continue to be produced in the countries that use the greatest part of the
      global vaccine supply. Thus, the CVI will rely on increased self sufficiency in
      vaccine production in the developing world and "shared development" of new and
      improved vaccines. The CVI's goal is to direct product development to meet the
      needs of immunization programs, but it must not neglect production. Thus, from
      the start, investment at the front end of the development and production sequence
      requires attention to the ultimate production capacity.

PMID- 8157460
TI  - The transfer of vaccine technology to developing countries. The Latin American
      experience.
AB  - Technological advances by developed countries are producing safer, more potent
      vaccines. In addition, the transfer of the technology of vaccine production to
      some developing countries has been taking place during the past five decades,
      thereby making possible the participation of developing countries in the
      production and supply of the essential biologicals that are required for
      immunization programs. Examples of successful transfers of technology, the
      decisive elements and factors that contribute to the transfers, and the major
      obstacles to such transfers are presented.

PMID- 8157461
TI  - New challenges in quality control and licensure. Regulation.
AB  - The Children's Vaccine Initiative (CVI) will result in profound changes in
      immunization practice. Before the CVI is fully developed, it will present
      numerous challenges to regulatory practice that will require new applications of
      existing ideas and innovative solutions to practical issues, especially in
      combining existing vaccines.

PMID- 8157463
TI  - The promise of new technologies.
AB  - Efforts to provide the benefits of immunization to the world's children have
      reached an important crossroad. While remarkable progress has been achieved in
      successfully administering six important childhood vaccines (diphtheria, tetanus,
      polio, pertussis, measles, and tuberculosis), the benefits of new vaccines, such
      as hepatitis B and Haemophilus influenzae type B glycoconjugate vaccines, have
      not been realized except in the most developed countries. The three reasons often
      cited to explain this problem include poor access to immunization services, the
      evolution of complex primary immunization schedules, and the additional expense
      associated with new vaccines, potentially depleting scarce resources. The
      establishment of the Children's Vaccine Initiative is an organized effort to
      improve immunization by both technological and organizational innovation.
      Simplification of the vaccination process can be achieved by developing new
      combination vaccines or reducing the number of immunizations with vaccines that
      stimulate protective immune responses. Improvements in the organization of
      efforts to immunize children will also enhance the prospects of protecting the
      world's children from infectious diseases. To achieve the goals articulated in
      the Declaration of New York, the issues of transition from the old to the new
      vaccines must be addressed. Research on vaccines and technological innovation at
      all levels will be required to achieve these goals.

PMID- 8157462
TI  - The desired field-performance characteristics of new improved vaccines for the
      developing world.
AB  - Although the vaccination initiatives undertaken during the past decade are the
      cornerstones for protecting the world's children and helping to ensure their
      survival and development, the vaccines currently being employed may become
      obstacles for further disease reduction or eradication. Their characteristics
      complicate or increase the burden on health care infrastructures to maintain or
      expand vaccine delivery systems. This paper examines an experience with the
      vaccine technologies that currently are being used by immunization programs in
      developing countries, illustrating the field problems and obstacles associated
      with their use. It discusses the advantages and benefits that would accrue if new
      or improved, heat-stable, multi-antigen vaccines that require only one or two,
      preferably oral, doses were to become available.

PMID- 8157464
TI  - Desirable immunologic characteristics for the development of an ideal vaccine.
AB  - The efficacy of vaccines for prophylactic use is a function of the immune
      response elicited by activated lymphocytes. Based on the current understanding of
      these responses, their induction, and the most effective ways to obtain long
      lived immunity, a novel protocol for the vaccination of children against seven
      childhood diseases, involving only two visits for vaccine administration, is
      proposed.

PMID- 8157465
TI  - Modern concepts in immune recognition and lymphocyte activation. Relevance for
      the development of useful vaccines.
AB  - Adaptive immunity requires both specific recognition of an antigen and its
      translation into appropriate lymphocyte responses. This paper reviews the
      striking differences in B- and T-lymphocyte antigen recognition, details the
      pathways for conversion of protein antigens into peptide-major histocompatibility
      complex molecule ligands for T-cell receptors, and summarizes the roles of
      costimulatory signals in lymphocyte activation. This information is used to
      suggest new approaches for the rational design of vaccines.

PMID- 8157466
TI  - Effective mucosal immunity. Current concepts for vaccine delivery and immune
      response analysis.
AB  - It is now established that the mucosal immune system is a separate entity and is
      regulated in a different fashion than that in peripheral lymphoid tissues (the
      systemic immune system). In this brief review, five selected areas within the
      field of mucosal immunity are discussed in the context of the goals for vaccines
      for the Children's Vaccine Initiative.

PMID- 8157467
TI  - Methodological issues in antiemetic studies.

PMID- 8157468
TI  - Pharmacokinetics, cerebrospinal fluid penetration, and metabolism of piroxantrone
      in the rhesus monkey.
AB  - Piroxantrone is an anthrapyrazole derivative with broad anti-tumor activity in
      vitro and less cardiac toxicity than the anthracyclines. The metabolic pathways
      and central nervous system penetration of piroxantrone have not been determined.
      In this study we examined the pharmacokinetic behavior of piroxantrone in plasma
      and cerebrospinal fluid in a non-human primate model. In addition, a urinary
      metabolite of piroxantrone was isolated and its cytotoxicity evaluated in vitro.
      The disappearance of piroxantrone from plasma after an intravenous dose of 150
      mg/m2 given over 60 minutes was biexponential with mean t1/2 alpha of 1.0 minutes
      and a mean t1/2 beta of 180 minutes. The mean area under the curve was 220
      microM.min and the clearance was 1420 ml/min/m2. Piroxantrone was not detectable
      in the cerebrospinal fluid. Piroxantrone and three other compounds not present in
      pre-treatment samples were detected in urine. The major urinary metabolite was
      isolated. Its cytotoxicity against MOLT-4 cells in vitro was at least one log
      less than that of piroxantrone. In addition, one of the other compounds detected
      in urine was determined to be a glucuronide conjugation product of the major
      metabolite. The results of this study may be useful in the interpretation of the
      activity and toxicity of piroxantrone in clinical trials.

PMID- 8157469
TI  - Antitumor activity of intoplicine (RP 60475, NSC 645008), a new benzo-pyrido
      indole: evaluation against solid tumors and leukemias in mice.
AB  - Intoplicine (RP 60475, NSC 645008) is a new 7H-benzo[e]pyrido [4,3-b] indole
      derivative which interacts with DNA and inhibits both topoisomerases I and II. In
      vitro it was found cytotoxic against various cell types with greater cytotoxicity
      towards solid tumor cells. We report here the anticancer activity of RP 60475
      against a variety of transplantable tumors of mice, and also its cross-resistance
      profile in leukemias. The end points used were % T/C (median tumor weight of the
      Treated over the Control x 100) and logCK (log10 cell kill total). RP 60475
      administered i.v. was found schedule-independent with a peak plasma level
      problem. It had a good therapeutic index and host recovery usually occurred 7.5
      days post last treatment. RP 60475 was found to be highly active against early
      stage colon 38 (T/C = 0%, 2.9 logCK) and could induce 5/5 complete regressions of
      advanced stage tumor. It was found active against colon adenocarcinoma 51 (T/C =
      3.6%, 1.9 logCK) and colon carcinoma 26 (T/C = 11.7%, 1.2 logCK). Most of the
      mammary adenocarcinomas were found very responsive, MA16/C (T/C = 0%, 2.8 logCK),
      MA14/A (T/C = 0%, 1.4 logCK), MA13/C (T/C = 0%, 3.1 log CK) and MA44 (T/C = 34%).
      Excellent activity was also observed against early stage pancreatic ductal
      adenocarcinoma 03 (T/C = 0%) and RP 60475 could achieve 5/5 complete regressions
      of upstaged tumor. Activity was also obtained on Glasgow osteogenic sarcoma (T/C
      = 0%, 3.3 logCK), on B16 melanoma (T/C = 14%, 1.3 logCK) and to a lesser extent
      on Lewis lung carcinoma (T/C = 33.2%). Evaluation of RP 60475 against leukemia
      sublines with acquired resistance, revealed that L1210/cisplatin and L1210/BCNU
      were not cross-resistant to RP 60475 whereas P388/vincristine was partially cross
      resistant to RP 60475 and P388/doxorubicin was cross-resistant to RP 60475. Based
      on RP 60475 broad activity against transplantable tumors of mice, its
      effectiveness against some resistant sublines, its original mechanism of action
      and its acceptable toxicological profile, this compound was selected for clinical
      trials.

PMID- 8157470
TI  - Effects of diflubenzuron and clanfenur on mouse bone marrow cells.
AB  - Diflubenzuron (DFB) and Clanfenur (CFN) belong to a group of compounds called
      Benzoylphenyl Ureas (BPUs). Several BPUs regulate cell growth in insects and/or
      inhibit growth of B-16 murine melanomas. In view of potential clinical use for
      these compounds, DFB and CFN were selected as examples of BPUs and tested for
      effects on hematopoiesis in C57Bl/6 mice housed in a conventional environment.
      DFB and CFN exhibit anti-tumor activity in mice, cause little or no morbidity and
      mortality and rather than causing bone marrow suppression, which is usual for
      anti-cancer drugs, these agents stimulate hematopoiesis in vivo and in vitro.
      Stimulation in vivo was evidenced by increased (up to 112%) peripheral blood
      granulocytes 6 days after a single injection and enhanced granulopoiesis
      (approximately 25%) in bone marrow up to 18 days after treatment. That effects of
      DFB and CFN were on hematopoietic stem cells were indicated by 47% and 48%,
      respectively, increases in numbers of CFUs and 97% and 95%, respectively,
      increases in CFUgm. Further, bone marrow cells treated in vitro contained about
      twice the number of CFUs and CFUgm as control bone marrow cells. Almost all of
      the increase in number of spleen colonies, whether derived from donors treated in
      vivo or bone marrow cells treated in vitro, was accounted for by a corresponding
      increase in number of undifferentiated colonies. These data indicate that DFB and
      CFN treatment enhance numbers of pluripotential stem cells both in vivo and in
      vitro. The mechanism of enhancement, direct or indirect, remains to be
      determined.

PMID- 8157472
TI  - Phase I pharmacokinetic study of DUP-937, a new anthrapyrazole.
AB  - DUP-937 is a new anthrapyrazole intercalator that inhibits DNA synthesis. A phase
      I trial was conducted in which DUP-937 was given in an intravenous bolus weekly
      for 3 weeks. Cycles were repeated every 5 weeks. Twenty men and 13 women with
      median ECOG performance status of 1 completed 74 cycles. The starting dose was
      0.55 mg/m2/week and doses were escalated to 16 mg/m2/week. Non-hematological
      toxicity was generally mild or moderate and consisted mainly of gastro-intestinal
      effects, fatigue, alopecia and local reactions. Grade 3 neutropenia was first
      documented at 7.36 mg/m2 and became more common at higher dose levels. Three of
      four patients had > or = grade 3 neutropenia at the 16 mg/m2 dose level.
      Thrombocytopenia was minimal. The dose-limiting toxicity was neutropenia and the
      maximum tolerated dose was 16 mg/m2 weekly for 3 weeks. Mean area under the curve
      (AUC) values increased with dose. Linear pharmacokinetics were observed as total
      body clearance (CLtb), half-life (t1/2) and volume of distribution (Vss) did not
      change with increasing doses. One partial remission in a patient with prostate
      carcinoma was documented.

PMID- 8157471
TI  - Phase I trial of mitoxantrone and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in patients with advanced solid malignancies.
AB  - PURPOSE: To determine the maximally tolerated dose (MTD) and pharmacokinetics of
      high-dose mitoxantrone and document the toxicities and side effects of
      mitoxantrone when administered with GM-CSF. PATIENTS AND METHODS: Twenty-three
      patients with advanced solid tumors were entered into a phase I and
      pharmacokinetic study. Mitoxantrone was administered at doses of 12, 21, 28, 32,
      37, and 48 mg/m2 on day 1; GM-CSF (5 micrograms/kg once or twice daily) was
      administered on days 2 to 14. Therapy was repeated every 3 weeks. Dose escalation
      continued in sets of three patients until the dose limiting toxicity (DLT) was
      observed. The DLT was based on hematologic, non-hematologic, and cardiac
      toxicity, and delay of therapy by more than 1 week due to toxicity. Plasma
      samples were assayed for mitoxantrone concentrations using high performance
      liquid chromatography (HPLC). RESULTS: Twelve patients required either
      mitoxantrone dose reductions or delays. DLT of neutropenia was observed at a
      mitoxantrone dose of 48 mg/m2/day. Therefore, we conclude the MTD was 37
      mg/m2/day. Myelosuppression appeared to be cumulative. Two patients were
      withdrawn from the study due to a drop in left ventricular ejection fraction
      (LVEF). Two of 23 patients experienced a partial response. The mean area under
      the curve (AUC) and peak mitoxantrone levels increased linearly with dose;
      triexponential elimination of mitoxantrone was observed. No statistically
      significant correlation was observed between either peak mitoxantrone level or
      AUC and duration of absolute neutrophil count (ANC) < 500/mm3. CONCLUSION: The
      use of GM-CSF allows administration of mitoxantrone at a dose greater than three
      times that given in standard therapy; treatment is well tolerated. Further
      studies are needed to determine whether mitoxantrone has cumulative cardiac or
      hematologic toxicity.

PMID- 8157473
TI  - Phase I clinical and pharmacokinetic study of menogaril (7-con-O-methylnogarol)
      in previously treated patients with acute leukemia.
AB  - Fifteen patients with relapsed or refractory acute leukemia were treated in this
      phase I study of menogaril (7-con-O-methylnogarol), a nogalamycin anthracycline
      derivative. Doses ranged from 50 mg/m2/day to 130 mg/m2/day, administered daily
      for 5 days. Pharmacokinetic studies were performed at each dose level and
      confirmed the findings of pharmacokinetic data derived from previous studies in
      patients with solid tumors. All patients experienced grade 4 hematologic toxicity
      and the dose limiting toxicity was mucositis. Two patients, one with acute
      myeloid leukemia and one with acute lymphoid leukemia, achieved complete
      responses. The AML complete response lasted 10 months and the ALL patient died in
      CR at 2+ months. Both patients were treated at a dose of 100 mg/m2/day for five
      days. At this dose, a second induction or consolidation course could be given
      without severe mucositis, and this is the dose recommended for further phase II
      studies in leukemia using this schedule.

PMID- 8157474
TI  - A phase II trial of piroxantrone in adenocarcinoma of the pancreas. A Southwest
      Oncology Group study.
AB  - Thirty-five evaluable patients with advanced adenocarcinoma of the pancreas were
      treated with piroxantrone at a dose of 150 mg/m2 intravenously every 21 days. No
      objective responses were observed (95% confidence interval 0%-10%). Toxicities of
      grade > or = 3 were primarily hematologic and were seen in 28 patients.
      Piroxantrone is inactive in pancreatic cancer and no further investigation of
      this agent in this tumor is recommended.

PMID- 8157475
TI  - VM-26 in gastric cancer. A Southwest Oncology Group study.
AB  - The Southwest Oncology Group conducted a trial of VM-26 (teniposide) in patients
      with advanced gastric cancer. VM-26 60 mg/m2 i.v. infusion over 30-45 minutes was
      given daily for 5 days every 21 days. Twenty-one eligible patients with
      measurable disease and a SWOG performance status of 0-2 were analyzed for
      response and toxicity. Partial responses were seen in 2 of the 21 eligible
      patients (9.5%). Median survival was 3.8 months. Severe of life-threatening
      toxicity was observed in 13/21 (62%) patients. This included two drug related
      deaths related to neutropenic sepsis and seven other patients with grade 4
      granulocytopenia (< 500/mm3). Liver dysfunction and hypotension were seen less
      often and were not dose limiting. Although the modest activity seen was
      comparable to that of VP-16 (etoposide) as a single agent, the hematologic
      toxicity observed in this trial would likely preclude further trials of VM-26
      (teniposide) in advanced gastric cancer.

PMID- 8157476
TI  - A phase II trial of gallium nitrate in advanced previously untreated colorectal
      cancer.

PMID- 8157477
TI  - Phase II trial of piroxantrone for advanced or metastatic soft tissue sarcomas. A
      Southwest Oncology Group study.
AB  - Piroxantrone is an anthrapyrazole compound undergoing phase II testing in a
      variety of diseases. The anthrapyrazoles are a series of compounds synthesized
      with the intent of maintaining the broad antitumor activity of anthracyclines,
      but with lessened cardiac toxicity. The Southwest Oncology Group (SWOG) conducted
      a phase II trial of piroxantrone in advanced soft tissue sarcoma. Treatment
      consisted of piroxantrone 150 mg/M2 administered intravenously over 1 hour every
      21 days. Twenty-five eligible patients were registered to the trial. Twenty-three
      patients received treatment and are fully evaluable for response and toxicity.
      Two partial responses were seen for an overall response rate of 9% (95%
      confidence limit 1%-28%). Abnormal cardiac ejection fraction occurred in five
      patients, and fatal congestive heart failure developed in one patient on study.
      Toxicities other than cardiac were tolerable. Based on the observed response rate
      and cardiac toxicity, further trials of piroxantrone in the treatment of soft
      tissue sarcoma do not appear warranted.

PMID- 8157478
TI  - A human metal responsive element-binding protein interacts with a homologous
      element of the mouse metallothionein-I gene.
AB  - Metallothionein (MT) is thought to play a central role in the detoxification of
      heavy metals, and thus studies on its regulation are toxicologically important.
      Heavy metal-dependent induction of MT genes is mediated by metal responsive
      elements (MREs) located upstream of the genes. Zinc regulatory factor (ZRF) is a
      zinc-dependent MRE-binding protein that was originally detected in HeLa cell
      nuclear extracts using the most proximal MRE of the human MT-IIA gene (hMREa) as
      a probe. We show that ZRF in HeLa cell nuclear extracts can also bind to the most
      potent MRE of the mouse MT-I gene (mMREd). This finding was further confirmed by
      using partially purified ZRF. Moreover, cadmium could not promote complex
      formation between ZRF and mMREd at any concentration tested, as is also the case
      with ZRF and hMREa. These observations suggest that the transcriptional
      regulatory system of MT genes by zinc is conserved beyond species.

PMID- 8157479
TI  - Exposure to segmental vibration and noise in orthopaedists.
AB  - The results of several field visits to orthopaedic clinics and the data obtained
      from a postal questionnaire were used to evaluate the segmental vibration and
      noise exposure levels in orthopaedists. The analysis of 54 (85.7%) complete
      questionnaires showed that hand-held plaster saws were used (Mean +/- SE, 12.3 +/
      1.7 min/week) more often than other tools. The mean frequency-weighted
      acceleration levels while using these tools were in the range of 2.3-2.4 m/s2.
      The A-weighted sound pressure levels in orthopaedic clinics while using the same
      instruments were in the range of 88.7-93.4 dB(A). Regarding the vibration
      magnitude and exposure time, segmental vibration seems not to be a serious
      problem in orthopaedists. However, the noise level produced from operating
      orthopaedic tools may have deleterious effects such as masking of speech
      communication among staff members. Patients' sleep or rest was thought to be
      disturbed by such noise levels.

PMID- 8157480
TI  - Changes in urinary cadmium excretion among pigment workers with improvement of
      the work environment.
AB  - Urinary Cadmium (Cd) levels were measured twice a year from 1986 to 1992 in five
      workers exposed to cadmium pigment dust. At the end of 1987, the work environment
      was improved, and urinary Cd was monitored in association with atmospheric Cd.
      The five subjects were exposed to cadmium dust at maximum concentrations of 0.857
      mg/m3 and 0.045 mg/m3, before and after the improvement, respectively. By
      arbitrarily setting the urinary Cd level of each worker before improvement at
      100, the values after improvement ranged from 41.7 to 94.6, yielding no
      significant difference. Although the environmental level of Cd was decreased by
      ten-fold or more, no significant decrease in urinary Cd could be detected.

PMID- 8157481
TI  - Analysis of various factors affecting vibration-induced white finger.
AB  - Forty-one stone quarriers were studied with regard to various factors affecting
      vibration-induced white finger (VWF), i. e., age, total operating time (TOT),
      body mass index (BMI), smoking, drinking, past history of diseases and
      sensitivity to cold in childhood. Subjects were asked about these factors by
      interview according to a questionnaire. TOT and BMI were significantly different
      between subjects with VWF (VWF group) and those without VWF (NON-VWF group). TOT
      was considered to be a great factor in stone quarriers. BMI was 21.6 (kg/m2) in
      VWF group against 24.0 (kg/m2) in NON-VWF group, which suggests that lean
      subjects may be susceptible to VWF. As for other factors such as age, smoking,
      drinking, past history of diseases and sensitivity to cold in childhood, our
      findings showed no significant difference between VWF group and NON-VWF group.

PMID- 8157482
TI  - Quantitation of gold labelling and antigens in immunolabelled ultrathin sections.

PMID- 8157483
TI  - The effect of age on dendrites in the rat superior cervical ganglion.
AB  - Intracellular injection of a biotinylated probe in fixed superior cervical
      ganglia followed by confocal microscopy was used to investigate the effects of
      age on the dendritic arborisation of sympathetic neurons in rats aged 6 wk (young
      adult), 7 months (fully grown adult) and 24 months (aged). In accordance with
      other studies considerable dendritic growth was observed during postnatal
      development. However, in old age dendritic growth did not continue, and
      significant atrophy was observed. Quantitation of neuronal morphology showed
      significant reductions in soma size, total dendritic length, number of branch
      points and total area of dendritic arborisation in old age. Unexpectedly,
      significant reductions in the numbers of primary dendrites were observed in
      maturity and in old age. Concomitant with this atrophy there was an increase in
      age-related morphological abnormalities. The similarities between the atrophy and
      dendritic abnormalities shown by our aged neurons and those seen in other studies
      of young adult sympathetic neurons following axotomy or trophic factor
      deprivation are discussed.

PMID- 8157484
TI  - Morphological specialisations of rat cranial nerve transitional zones.
AB  - Near their CNS-PNS transitional zones (TZs), many rat cranial nerve rootlets are
      subdivided to a marked degree by a reticulum of fine cytoplasmic processes. Some
      of the resulting compartments contain only a single myelinated fibre or a bundle
      of collagen fibrils. The compartments are aligned with the astrocytic tunnels in
      which the fibres lie as they traverse the CNS-PNS transitional zone. This marked
      subdivision may help to insulate individual fibres from one another, preventing
      functional interaction between them. Rootlet sheath cells commonly are closely
      apposed to, or interdigitate with, astrocyte processes of the TZ. These features
      may help to strengthen the delicate TZ. The TZ of the trochlear nerve includes a
      long, generally avascular, central tissue projection (CTP) into the proximal part
      of the nerve. This is connected to the brainstem and cerebellum by astrocytic
      bridges. In contrast to the CTP, which is generally avascular, these contain
      abundant blood vessels which may facilitate metabolic exchange in the trochlear
      TZ.

PMID- 8157485
TI  - A Phaseolus lectin anterograde tracing study of the tectorotundal projections in
      the domestic chick.
AB  - The projection from the chick optic tectum to the nucleus rotundus was
      investigated by iontophoresis of the anterograde tracer Phaseolus vulgaris lectin
      (PHA-L) into the optic tectum and by Golgi impregnation. PHA-L labelled fibres
      were observed within the ipsilateral nucleus rotundus and to course through the
      supraoptic decussation to the contralateral nucleus rotundus. They appeared
      similar to fibres evident in Golgi impregnated material. Before reaching the
      nucleus rotundus, PHA-L labelled fibres gave off short terminal branches in the
      caudoventral thalamic nucleus. Within the ipsilateral nucleus rotundus, the
      labelled fibres formed an extensive fibre net with a dense core and a less dense
      periphery. PHA-L labelled fibres in the contralateral nucleus rotundus exhibited
      a qualitatively similar but sparser distribution. There appeared to be a
      topographic representation of the optic tectum within the nucleus rotundus.
      Electron microscopy revealed that PHA-L labelled tectal fibres established
      asymmetric synapses with principal neurons in the nucleus rotundus.

PMID- 8157486
TI  - A scanning electron microscopy study of interactions between mouse granulated
      metrial gland cells and placental trophoblast cells in vitro.
AB  - Mouse granulated metrial gland cells were cocultured with labyrinthine placental
      cells and cell-cell contacts examined by scanning electron microscopy. Intimate
      contacts between granulated metrial gland cells and placental cells were observed
      and in some of these, differences in the surface morphology of the granulated
      metrial gland cells were observed. Some contact areas were suggestive of the
      granulated metrial gland cell monitoring the surface of potential target
      placental trophoblast cells prior to lysis.

PMID- 8157487
TI  - Fibre optic confocal imaging (FOCI) for subsurface microscopy of the colon in
      vivo.
AB  - Fibre optic confocal imaging (FOCI) is a new type of microscopy which has been
      recently developed (Delaney et al. 1993). In contrast to conventional light
      microscopy, FOCI and other confocal techniques allow clear imaging of subsurface
      structures within translucent objects. However, unlike conventional confocal
      microscopes which are bulky (because of a need for accurate alignment of large
      components) FOCI allows the imaging end to be miniaturised and relatively mobile.
      FOCI is thus particularly suited for clear subsurface imaging of structures
      within living animals or subjects. The aim of the present study was to assess the
      suitability of using FOCI for imaging of subsurface structures within the colon,
      both in vitro (human and rat biopsies) and in vivo (in rats). Images were
      obtained in fluorescence mode (excitation 488 nm, detection above 515 nm)
      following topical application of fluorescein. By this technique the glandular
      structure of the colon was imaged. FOCI is thus suitable for subsurface imaging
      of the colon in vivo.

PMID- 8157488
TI  - Atypical course of the rare accessory extensor carpi radialis muscle.
AB  - The description of a bilaterally well developed, bicipital and bipennate
      accessory extensor carpi radialis muscle is reported. The muscle arose between
      the origins of the long and short radial carpal extensor muscles and inserted by
      2 tendons into the 1st 2 metacarpal bones. The ulnar tendinous insertion was
      simultaneously the origin of abductor pollicis brevis. Both heads of the
      accessory extensor carpi radialis muscle were innervated by a branch of the deep
      branch of the radial nerve. The present observation supplements our knowledge on
      variations in the antebrachial and carpal regions, which are important in hand
      surgery.

PMID- 8157489
TI  - Case report: the cleidocervical muscle with speculation as to its origin.
AB  - The occurrence of a cleidocervical muscle, which arose from the anterior tubercle
      of the transverse process of the 6th cervical vertebra and was inserted onto the
      superior margin of the clavicle, is described. Detailed observations on its
      innervation, which was derived from the 5th cervical nerve, and its topographic
      anatomy suggest that the muscle originated from longus colli.

PMID- 8157490
TI  - Skeletal muscle in the pineal gland of the bat, Rhinopoma microphyllum: an
      ultrastructural investigation.
AB  - The unusual occurrence of skeletal muscle in the pineal gland of the bat
      Rhinopoma microphyllum is described. Individual muscle fibres were centrally
      placed and were incompletely encapsulated by a labyrinthine network of widened
      spaces filled with electron-dense material. The 2.4 micron long sarcomeres
      consisted of well developed A, I, H, M, and Z bands. A few myofibrils were
      oriented transversely within the same fibre. T system components, mitochondria
      and glycogen appeared normally distributed. Unmyelinated nerve bundles impinged
      upon the fibre but neuromuscular junctions were not observed. Several possible
      sources of origin for this tissue in the pineal gland are reviewed.

PMID- 8157491
TI  - Neural connections of the suprachiasmatic nucleus and medial hypothalamus of the
      Syrian hamster (Mesocricetus auratus).
AB  - The neural connections of brain areas involved in the control of circadian
      rhythms were investigated in the Syrian hamster by observing the anterograde and
      retrograde neural labelling resulting from injections of HRP-WGA into the
      suprachiasmatic nucleus (SCN) and subparaventricular zone (SPZ). The neural
      connections of these 2 brain areas in the strongly photoperiodic hamster are very
      similar to those in the more weakly photoperiodic rat. Two differences were
      observed: (1) in the rat, but not in the hamster, the SCN projects to the ventral
      geniculate nucleus and intergeniculate leaflet of the thalamus; and (2)
      reciprocal contralateral neural connections appear to be more numerous in the
      hamster than in the rat SCN. These differences may relate to the differences in
      photoperiodic sensitivity of the 2 species.

PMID- 8157493
TI  - The effects of undernutrition on connectivity in the cerebellar cortex of adult
      rats.
AB  - The effects of a 30 d period of undernutrition, followed in some animals by
      nutritional rehabilitation, on neuronal connectivity in adult rat cerebellum were
      investigated using the disector method. There was no significant difference
      between well fed (719 +/- 74, mean +/- S.E.) and undernourished (709 +/- 53)
      synapse-to-neuron ratios in 134-d-old rat cerebellar cortex, nor was there a
      significant difference in synapse-to-neuron ratios between control animals (941
      +/- 71) and previously undernourished rats (813 +/- 42) at 175 d of age. However,
      the age-related changes were significant (P < 0.05) in the controls, but not in
      the experimental group. It may be that the period of undernutrition caused subtle
      changes in the rehabilitating group which reduced the capacity for growth seen in
      well fed, matched control animals.

PMID- 8157492
TI  - The ventricular system of the pigeon brain: a scanning electron microscope study.
AB  - The fine structural features and regional differences of the ependyma in adult
      pigeons have been investigated by scanning electron microscopy. Pigeons of either
      sex were fixed with buffered glutaraldehyde (3%) and formaldehyde (0.5%) by
      intravascular perfusion. The brain was dissected using section planes adequate to
      expose each part of the ventricular system. The specimens were then dehydrated,
      critical point dried and sputtered with gold. Depending upon the distribution of
      cilia, microvilli and single cilia, different areas were recognised in the 4
      ventricles. The topographic locations of these areas were determined using the
      atlas of Karten & Hodos (1967). The medial surfaces of the 1st and 2nd lateral
      ventricles are more densely ciliated than the lateral surfaces. In the floor of
      the 4th ventricle the medial part is less ciliated than the lateral parts. The
      circumventricular organs (subseptal organ, organum vasculosum of the lamina
      terminalis, infundibulum, choroid plexus, subcommissural organ, area postrema)
      show very characteristic surfaces and are surrounded by a transitional zone with
      the nonspecialized ependyma. In contrast, in the paraventricular organ the
      transition to the nonspecialized ependyma is rather abrupt. The ependyma covering
      the trochlear nucleus appears densely ciliated, differing from that of the
      classic circumventricular organs. Finally, the existence of openings in the
      caudal medullary velum, which represent direct communications between the
      ventricles and the subarachnoid space, was demonstrated.

PMID- 8157494
TI  - Innervation of the ligament of the femoral head in the formosan rock monkey: a
      retrograde HRP tracing and ultrastructural study.
AB  - The innervation of the ligament attached to the femoral head of the Formosan rock
      monkey (Macaca cyclopis, Swinhoe) was investigated by means of the retrograde HRP
      tracing method and by electron microscopy. WGA/HRP was injected into the ligament
      of the left femoral head. Numerous neurons labelled with HRP were found in the
      ipsilateral lumbar sympathetic ganglia, from L1 to L7, with a peak in the L3 to
      L5 region. Labelled neurons were also found in the ipsilateral spinal dorsal root
      ganglia, from L1 to L7 and concentrated at L4. Ultrastructurally, the nerve
      fascicles to the ligament had an average diameter at 32.8 microns. They contained
      both myelinated and unmyelinated axons and accompanied the blood vessels. Sensory
      receptors were not found in the ligamentum proprium but free nerve endings were
      observed in the walls of the blood vessels. The present results indicate that the
      nerve fibres to the ligament of the femoral head may be involved in regulating
      blood vessel calibre in addition to having a sensory function.

PMID- 8157495
TI  - The chemical morphology of age-related changes in human intervertebral disc
      glycosaminoglycans from cervical, thoracic and lumbar nucleus pulposus and
      annulus fibrosus.
AB  - Hyaluronan (HA), chondroitin and keratan sulphates (CS, KS), collagen and dry
      weights were measured in the annulus fibrosus and nucleus pulposus of human
      cervical, thoracic and lumbar intervertebral discs aged 36-79 y. Alcian blue
      critical electrolyte concentration (CEC) staining of sections extended the
      results. The collagen, total polyanion, HA, CS and KS contents of the nucleus
      pulposus and annulus fibrosus were plotted for all 3 regions against age.
      Regional differences and age-related trends were found. For regional differences,
      the collagen content of the nucleus pulposus was highest in cervical discs and
      lowest in lumbar discs. In contrast, the total polyanion content of the nucleus
      pulposus was highest in lumbar discs and lowest in cervical discs. These
      differences were seen in fetal and adult discs. With respect to age-related
      trends, the collagen content of the annulus fibrosus was higher in adults and
      children than in neonates and infants. The collagen content of the nucleus
      pulposus increased with age in thoracic and lumbar discs, but it was consistently
      high in cervical discs. There was generally a downward trend of total polyanion
      and CS with increase in age. This was quite consistent for the annulus fibrosus
      in all regions and there were dramatic decreases in the lumbar nucleus pulposus
      in all adults compared with infants and children. These trends were least evident
      in the cervical nucleus pulposus where infant values were low. CS changes
      correlated with water content. HA and KS increased in all discs with increasing
      maturity. Oversulphated KS, absent from fetal discs, reached mature levels by 10
      y. Many of the changes occurred before maturity. Glycosaminoglycan (GAG) levels
      correlated with increasing compressive loads. Higher collagen levels in the
      cervical nucleus pulposus correlated with greater ranges of torsional and
      shearing strains in cervical discs. High GAG levels in cervical annulus fibrosus
      probably facilitate lamellar movements during torsional and flexional movements
      by lubrication and increase of tissue compressibility. Increased KS/CS ratios
      before maturity correlated with decreased disc blood supply. Ambient O2 tensions
      may determine KS/CS balance, the former consuming little O2 during biosynthesis.

PMID- 8157497
TI  - Quantitative TEM analysis of the barn owl basilar papilla.
AB  - The morphology of the barn owl's basilar papilla was quantitatively analyzed
      using TEM methods. The hair-cell (HC) parameters studied in the basal two-thirds
      of the papilla are remarkably constant. This large portion represents an extended
      high frequency area, or fovea [Koppl et al. (1993) J. Comp. Physiol. A 171, 695
      704]. In the apical third of the papilla, in contrast, these parameters change
      regularly, as they do in other avian species. The HC in the most neural position
      remain morphologically more similar along the entire length of the papilla than
      do neighbouring cell rows. In the behaviourally most important frequency range (4
      9 kHz), the afferent innervation of these neural HC is very dense and is
      reminiscent of the situation in mammals. Differences in HC morphology also
      indicate a specialization of the extreme apex of the papilla in the barn owl.
      Avian HC morphology is not correlated with a specific place along the basilar
      papilla but rather with the best frequency. Based on the body of recent
      quantitative morphological data on avian HC structure, a modified definition of
      HC types in birds is suggested (while keeping introduced terms): THC (tall hair
      cells) are defined as all those HC with afferent (and normally also efferent)
      innervation. SHC (short hair cells) are the (more specialized) HC without
      afferent innervation; obviously their function is restricted to the papilla
      itself.

PMID- 8157496
TI  - Regional and temporal changes in the synthesis of matrix metalloproteinases and
      TIMP-1 during development of the rabbit mandibular condyle.
AB  - Connective tissues synthesise and secrete a family of matrix metalloproteinases
      (MMPs; collagenases, gelatinases and stromelysins) capable of degrading all the
      components of connective tissue matrices at physiological pH. We document the
      patterns of synthesis and distribution of MMPs and the tissue inhibitor of
      metalloproteinases-1 (TIMP-1) within the developing rabbit mandibular condyle
      using immunofluorescence microscopy. MMPs and TIMP-1 were detected both as bright
      intracellular accumulations within Golgi vesicles and also as diffuse matrix
      bound extracellular deposits. Cells in the articular zone, proliferative zone,
      condylar cartilage and bone of the mandibular ramus were shown to produce all 3
      classes of MMPs and TIMP-1 with the exception of stromelysin, which was not
      synthesised by cells of the bone of spongiosum. Temporal synthesis of MMPs and
      TIMP-1 within these regions varied during the period 18 d postcoitum to 14 d
      postnatum. Our results document unique patterns of MMP and TIMP-1 synthesis
      during embryonic and early postnatal development of condylar cartilage and
      support the concept that cells synthesise and secrete MMPs and TIMP-1 before
      undergoing proliferation and hypertrophy. A comparison of these results with data
      in the rabbit growth plate show many similarities, but some differences exist
      that probably reflect differences in the modes of growth of the 2 cartilages.

PMID- 8157498
TI  - Transepithelial voltage and resistance of vestibular dark cell epithelium from
      the gerbil ampulla.
AB  - Transepithelial voltage (Vt) and resistance (Rt) were measured across the dark
      cell epithelium of the gerbil ampulla using a micro Ussing chamber of improved
      design in order to test the view that the histologically similar epithelia in the
      utricle and in the ampullae exhibit similar electrophysiologic functions. Vt was
      found to be 8.0 +/- 0.3 mV and Rt was 11.6 +/- 0.4 ohm-cm2 (N = 179) when both
      sides of the tissue were perfused with symmetric perilymph-like solution. The
      equivalent short circuit current (Isc = Vt/Rt) was 712 +/- 18 microA/cm2 (N =
      179). Isc was reduced from 638 +/- 60 to 48 +/- 16 microA/cm2 (N = 14) by
      basolateral perfusion of 10(-3) M ouabain and from 538 +/- 27 to 27 +/- 4
      microA/cm2 (N = 15) by basolateral perfusion of 5 x 10(-5) M bumetanide.
      Basolateral K+ steps (Na+ substitution) from 3.6 to 25 mM increased Vt from 6.5
      +/- 0.5 to 12.2 +/- 0.6 mV and reduced Rt from 9.7 +/- 0.7 to 7.4 +/- 0.5 ohm-cm2
      (N = 43). Apical K+ steps from 3.6 to 25, to 100 mM or to 145 mM led to a
      decrease in both Vt and Rt. The steady state Vt during apical perfusion of 145 mM
      K+ was near zero. Upon return to 3.6 mM K+, Vt transiently overshot its original
      level. Apical Cl- steps from 150 to 50 mM (gluconate substitution) monophasically
      decreased Vt from 5.9 +/- 0.7 to 4.1 +/- 0.8 mV (N = 15) and increased Rt from
      9.6 +/- 1.3 to 12.0 +/- 1.5 ohm-cm2 (N = 14).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157499
TI  - Hair cells of different shapes and their placement along the frog crista
      ampullaris.
AB  - The list of distinguishing morphological features of hair cells includes: Type I
      and Type II afferent innervation, and length, shapes and arrangements of stereo-
      and kinocilia. We now add to this list the shapes of the hair cells themselves
      and their placement within the mechanosensory organ, in this case the
      semicircular canal. Although hair cells of the crista ampullaris of the frog are
      only of Type II they may now be further classified into three sub-groups
      according to shape: club-, cigar- and pear-shaped. The cigar- and club-shaped
      hair cells are each about 40% while the pear-shaped cells are about 20% of the
      total numbers of hair cells in the crista. The differently-shaped hair cells also
      distribute differently along the crista. The cigar- and club-shaped are more-or
      less uniformly distributed with somewhat higher concentrations at the ends of the
      crista than in the center. The pear-shaped hair cells, on the other hand, are
      mostly concentrated toward the center of the crista. This distribution of the
      pear-shaped hair cells, and their shape is reminiscent of the distribution of
      calyceal endings (Type I hair cell) in the cristae of amniotes [Goldberg et al.,
      Hear. Res. 49, 89-102 (1990) in Chinchilla; Fernandez et al., Soc. Neurosci.
      Abstr. 17, 312 (1991) in Monkey]. There are some quantitative differences between
      hair cells of the same shape but from different portions of the crista. For
      instance, pear-shaped hair cells of the center are generally of greater cross
      sectional area than those of the ends.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157500
TI  - Improvement in sensorineural auditory threshold of the guinea-pig fetus following
      delivery.
AB  - The human fetus in utero is hypoxic relative to the neonate due to differences
      between placental and pulmonary oxygenation. Comparable degrees of hypoxia
      induced in young and adult animals caused an elevation in hearing threshold of a
      sensorineural nature. It was hypothesised therefore that the human fetus may also
      have such an elevation of threshold. This was tested in this study by recording
      ABR thresholds to bone conducted stimuli in fetal guinea-pigs that were near full
      term and again in the same animals, after delivery and consequent pulmonary
      oxygenation. In every animal studied (n = 9), the neonatal threshold was better
      than that in the fetus. In those fetuses in which a response could be recorded (n
      = 5), the neonatal threshold was on average 20 dB better than in the fetus. These
      findings are probably due to a depression of the endocochlear potential induced
      by the relatively hypoxic state of the fetus. The hypoxic state would lead to a
      reduced transduction current in the hair cells in response to a stimulus and an
      elevated hearing threshold. At birth, with the shift to pulmonary oxygenation,
      the neonate becomes normoxic, the endocochlear potential rapidly reaches near
      maximal levels and threshold is improved.

PMID- 8157501
TI  - Binaural processing in the dorsal nucleus of the lateral lemniscus.
AB  - We studied the binaural properties of 72 neurons in the dorsal nucleus of the
      lateral lemniscus (DNLL) of the mustache bat. There are six main findings: 1)
      Conventional EI neurons that were excited by stimulation of the contralateral ear
      and inhibited by ipsilateral stimulation, comprise the majority (80%) of binaural
      DNLL cells. 2) For most EI neurons the quantitative features of their interaural
      intensity disparity (IID) functions, maximum inhibition, dynamic range and 50%
      point IIDs, were largely unaffected by the absolute intensity at the
      contralateral ear. 3) Although the net effect of the inhibition evoked by
      ipsilateral stimulation was to suppress discharges evoked by contralateral
      stimulation, our results indicate that the inhibitory inputs can act in three
      different ways. The first was a time-intensity trade, where increasing the
      intensity at the ipsilateral ear evoked inhibitory effects with progressively
      shorter latencies. The second way was that the latency of inhibition did not
      appear to decrease with ipsilateral intensity, but rather increasing ipsilateral
      intensity appeared only to increase the strength of the inhibition. The third way
      was that the lowest effective ipsilateral intensity suppressed the first spikes
      evoked by the contralateral stimulus and higher ipsilateral intensities then
      suppressed the later discharges of the train. Each of these inhibitory patterns
      was seen in about a third of the cells. 4) Neurons that had more complex binaural
      properties, such as the facilitated EI neurons (EI/F) and neurons that were
      driven by sound to either ear (EE neurons), represented about 20% of the binaural
      population. There were two types of EE neurons; those in which there was a simple
      summation of discharges evoked with certain IIDs, and those in which the spike
      counts to binaural stimulation at certain IIDs were greater than a summation of
      the monaural counts and thus were facilitated. 5) All binaural neurons were
      strongly inhibited with IIDs that favored the ipsilateral ear. Our findings
      indicate that the more complex binaural types, the facilitated EI neurons (EI/F)
      as well as the two types of EE neurons, may be constructed from conventional EI
      neurons by adding inputs from several sources that impart the more complex
      features to these neurons. We propose four circuits that could account for the
      different binaural response properties that we observed. The circuits are based
      on the known connections of the DNLL and the neurochemistry of those connections.
      Finally, we compared the binaural properties of neurons in the mustache bat DNLL
      with those of neurons in the mustache bat inferior colliculus and lateral
      superior olive.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8157502
TI  - Expression of actin isoforms in the guinea pig organ of Corti: muscle isoforms
      are not detected.
AB  - The specificity of antibodies to actin was assayed by use of immunoblots and
      histological sections of control tissues enriched for each of six different
      isoforms. On immunoblots, all antibodies stained at most one band of protein in
      most of the control materials, with a molecular weight of approximately 43 kDa.
      Their pattern of staining of muscle and nonmuscle tissues indicated their isoform
      specificity. On tissue sections, immunocytochemical staining demonstrated
      cellular and subcellular localization of the different isoforms. Once
      characterized with regard to specificity, these antibodies were used to probe
      actin in the guinea pig organ of Corti. None of the four muscle isoforms of actin
      were found in either immunoblots or tissue sections of the organ of Corti. Both
      beta- and gamma-cytoplasmic isoforms of actin were present in hair cells and
      supporting cells. This leaves open to investigation the role which cytoplasmic
      actins play in these cells of the organ of Corti.

PMID- 8157503
TI  - ATP-induced cytoplasmic [Ca2+] increases in isolated cochlear outer hair cells.
      Involved receptor and channel mechanisms.
AB  - Outer hair cells (OHC) of the mammalian cochlea are thought to preprocess the
      sound signal by active movements, which can be induced by electrical or chemical
      stimulation, e.g. depolarization evoked by high [K+] or increased cytoplasmic
      [Ca2+]. Extracellular ATP has been found to induce cytoplasmic [Ca2+] increases
      in OHC but involved mechanisms have not been elucidated. Cytoplasmic [Ca2+] was
      measured in non-enzymatically isolated single OHC using Fura-2 microspectrometry.
      Results, using ATP/derivatives and other P2-purinergic receptor (P2R) ligands, as
      well as Ca(2+)-channel blockers and pertussis toxin, revealed several signal
      transduction pathways that increase cytoplasmic [Ca2+] in OHC: a P2-purinergic
      receptor (P2R)--G-protein--effector (phospholipase C or an ion channel) system
      and a voltage-dependent Ca2+ channel. Agonist potency studies denote a pattern
      analogous to that found in skeletal muscle, i.e. ATP-alpha-S > ATP = 2-methyl-S
      ATP >> ADP > alpha,beta-methylene-ATP, but no activation by ADP beta F or UTP,
      leaving a choice of P2y or P2zR subtypes. The latter possibility gained strength
      from calculations showing that up to 8% of ATP may have formed the P2zR agonist
      ATP4- in the experimental medium. Experiments in Ca(2+)-free medium and with
      pertussis toxin revealed that the main Ca2+ source was intracellular. Pertussis
      toxin did not affect [Ca2+] increase induced by carbachol. Acetylcholine,
      administered a few seconds before ATP, did not affect total cytoplasmic [Ca2+]
      increases. Induced cytoplasmic [Ca2+] increases were high enough (> 500 nM at 50
      microM ATP/derivatives) to hyperpolarize the OHC membrane by opening K(+)
      channels and decreased little with time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157504
TI  - Tuned phasic and tonic motile responses of isolated outer hair cells to direct
      mechanical stimulation of the cell body.
AB  - Guinea pig outer hair cells (OHCs) isolated from the two apical turns of the
      cochlea and firmly attached to a suction pipette, were subjected to the stimulus
      of the near-field (particle) displacements of a calibrated oscillating fluid jet
      aimed at the lateral cell walls. The longitudinal length changes of the OHCs in
      response to stimulation, in a direction orthogonal to that of the fluid jet, were
      recorded by a photodiode array. The response had two components; a phasic length
      change which followed the frequency of the particle displacement of the jet cycle
      by cycle, and a tonic length change which took several milliseconds to develop
      depending on the magnitude of the mechanical stimulus. When the hair cell changed
      length the lateral walls of the OHC moved in antiphase, moving apart during
      shortening and together during lengthening. With increased stimulus level the
      phasic response grew in proportion to the stimulus magnitude and began to
      saturate at the highest stimulus levels, while the tonic response grew in
      proportion to the square of the stimulus magnitude. Both the direction of the
      tonic length change and the phase of the phasic component could alter with the
      level of stimulation. Isolevel and isoresponse-frequency functions of both the
      tonic and phasic length changes revealed that both response types were tuned to
      similar resonant frequencies (RF) between 150 and 2500 Hz. The phase of the
      phasic length change began to lag at frequencies just below the RF, lagged by
      about 90 degrees at the RF and lagged by a further 90 degrees at frequencies
      above RF. The frequency response properties of the OHCs closely corresponded to
      those of a damped, forced, mechanical resonance. The tonic response disappeared
      and the phasic response was reduced at low-levels as a consequence of intense
      mechanical stimulation and with time.

PMID- 8157505
TI  - Expression of BDNF and NT-3 mRNA in hair cells of the organ of Corti:
      quantitative analysis in developing rats.
AB  - Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are
      synthesized by inner and outer hair cells of the developing organ of Corti. This
      raises the possibility that the reorganization of cochlear innervation patterns
      that occurs postnatally may be influenced by changing levels of neurotrophin
      expression. To determine if differential expression of BDNF or NT-3 in the inner
      and outer hair cells correlates with the reorganization of afferent and efferent
      innervation, we used in situ hybridization techniques to quantify relative levels
      of transcript biosynthesis in hair cells of developing rats. BDNF transcripts
      decreased in inner and outer hair cells from E17 to insignificant levels at P4.
      NT-3 expression was high at E17 in inner and outer hair cells, decreased in outer
      hair cells by E21, in inner hair cells by P1, remained low during the first
      postnatal week and was increased in the adult. The decreases in expression of
      both neurotrophins at birth precede the retraction of afferent nerve terminals
      from outer hair cells. BDNF and NT-3 transcription decreases substantially in
      outer hair cells between E21 and P4 when efferent innervation begins, indicating
      target biosynthesis of these neurotrophins is not likely to be instrumental in
      efferent target selection.

PMID- 8157506
TI  - Physiological evidence for ipsilateral inhibition in the lateral superior olive:
      synaptic responses in mouse brain slice.
AB  - The incidence of ipsilateral inhibition in the lateral superior olive (LSO) was
      examined in a brain slice preparation of the mouse superior olivary complex. A
      400 microns brain slice was taken in the frontal plane and maintained in a warm,
      oxygenated saline solution. Intracellular recordings were made from the LSO with
      micropipettes filled with 4 M potassium acetate. Synaptic responses were elicited
      by electrical stimulation of the trapezoid body in different slices at various
      locations between the cochlear nucleus and the ipsilateral superior olivary
      complex (SOC). The results show that ipsilateral stimulation can evoke inhibitory
      as well as excitatory postsynaptic potentials. The ipsilateral IPSPs have short
      latencies and are elicited by stimulation of the trapezoid body at any point
      along its course between cochlear nucleus and LSO. Short-latency IPSPs can also
      be produced by direct stimulation of the ventral cochlear nucleus itself.
      Ipsilateral IPSPs are blocked by low concentrations of the glycine antagonist,
      strychnine. In addition, bath application of sodium pentobarbital in one case
      eliminated ipsilateral IPSPs without eliminating EPSPs. The results suggest that
      there is a rapidly conducting, glycinergic pathway from cochlear nucleus through
      the trapezoid body to the LSO on the same side of the brain. This pathway is
      probably served by either a direct projection from the ventral cochlear nucleus
      to the LSO or an indirect one from cochlear nucleus to LSO through the lateral
      nucleus of the trapezoid body (LNTB).

PMID- 8157507
TI  - Construction of a cDNA library from microdissected guinea pig crista ampullaris.
AB  - Poly(A) RNA was isolated from microdissected guinea pig crista ampullaris
      epithelium and converted into cDNA with RNase H- murine leukemia virus reverse
      transcriptase. After size fractionation, the cDNA was directionally ligated into
      the vector pSPORT 1 and the plasmids electroporated into E. coli. The library was
      found to have 1.6 x 10(7) independent colonies with 5% of the colonies lacking an
      insert. Thirty randomly selected colonies were checked for inserts and the
      average insert size was 833 base pairs with a range of 400 to 2300 base pairs.
      The library was screened with a beta-actin guinea pig cDNA probe and 0.16% of the
      colonies contained an insert hybridizing to the probe.

PMID- 8157508
TI  - Simulation of free-field sound sources and its application to studies of cortical
      mechanisms of sound localization in the cat.
AB  - We synthesized a set of signals (clicks) for earphone delivery whose waveforms
      and amplitude spectra, measured at the eardrum, mimic those of sounds arriving
      from a free-field source. The complete stimulus set represents 1816 sound-source
      directions, which together surround the head to form a 'virtual acoustic space'
      for the cat. Virtual-space stimuli were delivered via calibrated earphones sealed
      into the external meatus in cats under barbiturate anesthesia. Neurons recorded
      in AI cortex exhibited sensitivity to the direction of sound in virtual acoustic
      space. The aggregation of effective sound directions formed a virtual space
      receptive field (VSRF). At 20 dB above minimal threshold, VSRFs fell into one of
      several categories based on spatial dimension and location. Most VSRFs were
      confined to either the contralateral (59%) or ipsilateral (10%) sound hemifield.
      Seven percent spanned the frontal quadrants and 16% were omnidirectional. Eight
      percent fit into no clear category and were termed 'complex'. The size, shape,
      and location of VSRFs remained stable over many hours of recording. The results
      are in essential agreement with free-field studies. VSRFs were found to be shaped
      by excitatory and inhibitory interactions of activity arriving from the two ears.
      Some cortical neurons were found to preserve the spectral information in the free
      field sound which was generated by the acoustical properties of the head and
      pinna, filtered by the cochlea and transmitted by auditory nerve fibers.

PMID- 8157509
TI  - Intercellular contacts between chick stereocilia after acoustic overstimulation.
AB  - The goal of this study was to analyze the distribution of actin and the shape of
      stereocilia of chick hair cells that survive acoustic trauma. Chicks were exposed
      to intense octave band noise for 4 h. They were killed either immediately after
      the exposure, after 6 or after 72 h. The basilar papillae were examined using
      scanning electron microscopy and fluorescence microscopy, with phalloidin as an
      actin-specific probe. Injured hair cells which survived the trauma displayed
      disorganized stereocilia bundles, elongated stereocilia, and supernumerary
      stereocilia bundles. Tips of stereocilia in the damaged region of the basilar
      papilla appeared to be in contact with tips of stereocilia of neighboring hair
      cells. These contacts may represent 'stress links' which appear in traumatized
      hair cells. These results show that substantial changes in stereocilia occur
      within hours of exposure to intense noise. We speculate that surviving hair cells
      may play a role in the process of repair of the basilar papilla after noise
      trauma and that the changes in stereocilia structure described here are related
      to this role.

PMID- 8157510
TI  - Neurotrophin and neurotrophin receptor mRNA expression in developing inner ear.
AB  - Receptors which bind the neurotrophins NGF, BDNF, NT-3 and NT-4/5 were shown to
      be present in cochlear and vestibular ganglion cells during development, implying
      a neurotrophic role for these molecules in the inner ear. We have found by in
      situ hybridization that cochlear and vestibular sensory epithelial cells express
      BDNF and NT-3 mRNAs, but neither NGF or NT-4 mRNAs, in mouse embryos from
      embryonic day (E)11.5 through postnatal day (P)1. NT-3 mRNA was expressed
      throughout the sensory epithelium whereas BDNF mRNA appeared to be localized in
      hair cells (vestibular) and epithelial precursors of hair cells (cochlea). BDNF
      mRNA was also expressed in a subpopulation of cells in the cochleovestibular
      ganglion at E11.5 and E12.5. Additionally, cochlear and vestibular neurons
      contained mRNAs encoding the neurotrophin receptors p75 and trkB. TrkA mRNA was
      transiently expressed in cochleovestibular ganglion cells at E12.5. These data
      suggest that BDNF and NT-3 play a role in cochleovestibular neuron survival and
      neurite outgrowth during development in the inner ear.

PMID- 8157511
TI  - Effect of implant sequence and dose on feedlot cattle performance.
AB  - Studies were conducted to evaluate the effects of delayed implanting or the use
      of a low-dose implant followed by a higher-dose implant in feedlot cattle. In the
      first study, 150 steers were allotted to 15 pens (three pens/treatment) and
      assigned to a nonimplant treatment (control), a single zeranol (36 mg) implant
      (R), or a double zeranol implant (DR) administered at the start of a 140-d
      finishing period, or a single zeranol implant administered at the start of an 80
      d growing period, followed by a single (RR) or double (RDR) zeranol implant
      administered at the start of the finishing period. Steers managed under the DR,
      RR, and RDR implant schemes had greater (P < .10) finishing period gains and
      intakes than the control steer group. However, only DR and RDR steer groups had
      improved (P < .10) finishing period feed conversions compared with control
      steers. In combined growing and finishing periods, the RDR steer group displayed
      the lowest (P = .12) feed:gain ratio. In a second trial, conducted concurrently
      to the zeranol trial, steers that did not receive an initial implant containing
      20 mg of estradiol benzoate plus 200 mg of progesterone (S) but were subsequently
      implanted twice, once at the start of the finishing period and again 80 d later,
      had a lower (P < .11) finishing period feed:gain ratio (6.08 vs 6.51) than steers
      implanted all three times.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157512
TI  - Effect of delayed breeding on the endocrinology and fecundity of sows.
AB  - The effect of serving sows at first or second estrus after weaning was determined
      using 114 Camborough sows (Parities 1 to 8). Eighty sows were paired according to
      weaning-to-estrus interval and parity. One sow of each pair was bred at first and
      the other at second estrus after weaning. A further 27 sows were catheterized on
      d 3 after weaning or d 20 of the first estrous cycle and bred at first or second
      estrus, respectively. Blood samples were taken every 30 min from 0800 to 1330 on
      the day after catheterization, every 6 h from catheterization until 1 d after
      standing estrus, and every 12 h for a further 3 d. Of the 80 sows, litter size
      increased (P < .002) by breeding Parity 1 and 2 sows at second rather than at
      first estrus (10.4 vs 12.8 total pigs born). These increases in litter size were
      achieved in the absence of any significant changes in sow weight or backfat
      during lactation and between weaning and breeding, and predicted changes in fat
      and protein during lactation. Similar but nonsignificant results (P = .15) were
      observed for the 27 catheterized sows. Plasma progesterone concentrations
      measured 50 h after the preovulatory LH surge were higher in Parity 1 and 2 sows
      bred at second rather than at first estrus (5.4 +/- .7 vs 3.7 +/- .3 ng/mL, P <
      .04). Sows of Parity 1 and 2 bred at first rather than at second estrus had
      higher plasma IGF-I (P < .05) and glycerol (P < .001) concentrations and tended
      to have lower preprandial insulin concentrations (P = .09).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8157513
TI  - Effects of Synovex C implants on growth rate, pelvic area, reproduction, and
      calving performance of replacement heifers.
AB  - Two trials were conducted to evaluate effects of Synovex C implants on
      replacement heifers, given at two different ages. Crossbred heifer calves (n =
      370) were allotted to four treatments: 1) nonimplanted controls, 2) implanted at
      2 mo, 3) implanted at 6 mo, and 4) implanted at both 2 and 6 mo of age. Heifers
      implanted at 2 mo gained 7 kg more (P = .01) by 6 mo than those not implanted at
      2 mo. No differences were found in 22-mo weights. All implanted heifers had
      larger (P = .01) yearling pelvic area than controls. All heifers implanted at 6
      mo continued to have larger (P = .01) pelvic area at 22 mo. All implanted heifers
      had higher (P = .05) occurrence of non-ovulatory estrus. No differences were
      found among treatments in percentage of heifers puberal before breeding, in
      estrus first 21 d of breeding, or in first-service conception rate. In only one
      trial, pregnancy first 21 d and total pregnancy in 63-d breeding season were
      decreased (P = .05) by implanting at 6 mo. At subsequent calving, an interaction
      existed between the effects of the 2- and the 6-mo implant for calf birth weight
      and pelvic area:birth weight ratio. A single implant at either 2 or 6 mo
      decreased (P = .01) calving difficulty score; and implanting at both 2 and 6 mo
      showed the greatest reduction in calving difficulty. Implants had no significant
      long-term effects on reproduction or calf production of 2-yr-old cows.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8157514
TI  - The influence of the mineral level in drinking water and the thermal environment
      on the performance and intestinal fluid flux of newly-weaned pigs.
AB  - The effects of drinking water containing high levels of dissolved minerals
      including sulphate (HMW) and a chilled environment on the performance of newly
      weaned pigs were evaluated in three replicate 10-d trials. In each trial, 12, 28
      d-old pigs were taken from the sow and allocated by weight and litter to
      treatment groups following a 2 x 2 factorial arrangement of HMW vs low-mineral
      drinking water (LMW) and normal (heat lamp) vs chilled (21 degrees C) pen
      temperature. No interactive effects of water mineral level and pen temperature on
      any of the measurements of health and productivity were found. Pigs given the HMW
      consumed more water on d 7 to 10 and 1 to 10 (P < .05) and more feed from d 4 to
      6, 7 to 10, and 1 to 10 (P < .05), had greater weight gains from d 7 to 10 and 1
      to 10 (P < .05), and had higher scour scores on d 4 and 7 (P < .05). Pigs
      maintained in a chilled environment had lower body weights on d 3, 6, and 10 (P <
      .05), lower feed conversion efficiency from d 7 to 10 (P < .05) and 1 to 10 (P <
      .05) and 7 to 10 (P < .01). Pen temperature had no effect on feed intake and
      scour scores. There was a correlation (P < .05) between feed intake and growth
      rates throughout the trial, between feed intake and water intake on d 4 to 6, 7
      to 10, and 1 to 10, and between water intake and growth rate on d 7 to
      10.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157515
TI  - Lipopolysaccharide-induced sickness behavior in pigs is inhibited by pretreatment
      with indomethacin.
AB  - Many of the behavioral responses following acute bacterial or viral infection are
      now considered important for maintaining homeostasis during inflammation. In the
      present study, we extend this concept to pigs (16 crossbred barrows) by
      demonstrating that lipopolysaccharide (LPS, .5, 5, or 50 micrograms/kg BW) from
      Escherichia coli injected i.p. reduces feed intake, decreases activity, and
      elevates body temperature. To determine whether any of these effects could be
      mediated via a prostaglandin (PG)-dependent mechanism, a second experiment with
      16 crossbred barrows was conducted. Barrows were pretreated with indomethacin
      (IND, 5 mg/kg BW [a cyclooxygenase inhibitor]), and their behavior and body
      temperature following a challenge i.p. injection of LPS (5 micrograms/kg BW) were
      assessed. Pretreatment with IND inhibited the anorexia and inactivity caused by
      LPS, suggesting that the behavioral effects of LPS are dependent on activation of
      a PG system. Lipopolysaccharide alone, however, did not elevate body temperature
      in this case; thus, the involvement of PGs in this response was not determined.
      Collectively, these data indicate that pigs respond to LPS by reducing feed
      intake, decreasing activity, and becoming febrile. The ability of IND to inhibit
      behavioral effects of LPS is consistent with the hypothesis that a PG system is
      involved in mediating sickness behavior. Perhaps, by altering the activity of
      cyclooxygenase it is possible to enhance or inhibit the behavioral symptoms of
      sickness in pigs.

PMID- 8157516
TI  - Bioelectrical impedance analysis for the prediction of fat-free mass in lambs and
      lamb carcasses.
AB  - Ninety-eight commercial crossbred lambs, average weight 55.1 kg (+/- 4.95), were
      used to evaluate bioelectrical impedance analysis (BIA) as a prediction method
      for fat-free tissue from live lambs and lamb carcasses. Lambs were transported to
      the abattoir, restricted from feed for 10 h, weighed (LWt), and measured for body
      resistance (Rs, ohms), body reactance (Xc, ohms), and distance between detector
      terminals (L, cm). Following slaughter, hot carcasses were weighed (HCWt; average
      31.4 +/- 2.8 kg) and impedance measurements of Rs, Xc, and L were recorded from
      readings on the dorsal and lateral sides of the carcasses. Temperatures (average
      = 39.2 degrees C) were recorded. Carcasses were chilled for 24 h. Cold carcass
      weights (CWt; average 31.1 +/- 2.8 kg) and temperatures (average = 1.0 degrees C)
      were recorded and BIA measurements were repeated. Carcasses were split down the
      midline and right sides were ground three times and sampled for chemical analysis
      of fat, moisture, ash, and protein. Fat-free mass (FFM) was calculated as [Wt-(Wt
      x %Fat)]. Fat-free soft tissue (FFST) was calculated as the sum of carcass
      chemical protein and carcass water. Regression equations predicting fat-free
      tissue for the live lambs (FFMlive and FFSTlive), hot carcasses (FFMhot and
      FFSThot), and cold carcasses (FFMcold and FFSTcold) were developed. The
      independent variables LWt, Rs, and Xc accounted for 77.7% (residual mean square
      error [RMSE] = 1.97 kg) of the variation in FFMlive and 78.6% (RMSE = 1.78 kg) of
      the variability of FFSTlive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157517
TI  - The effects of high-forage diets with added palm oil on performance, plasma
      lipids, and carcass characteristics of ram lambs with initially high or low
      plasma cholesterol.
AB  - The objectives of this study were to examine the interaction between added palm
      oil in high-forage diets and initial concentration of plasma cholesterol on
      performance, plasma lipids, and carcass characteristics of growing ram lambs.
      Thirty-two Hampshire-Suffolk ram lambs (initial BW = 34.4 kg) were assigned to a
      2 x 2 factorial design consisting of diet (basal [NPO] or 10.7% added palm oil
      [PO]) and initial plasma cholesterol concentration (high mean = 50 mg/dL [HC] or
      low mean = 38 mg/dL [LC]; SEM = 2; P = .01). The lambs were individually fed
      diets (77% forage-23% concentrate) that contained 16.0% CP, 2.14 Mcal of ME/kg
      (NPO), and 2.62 Mcal of ME/kg (PO). Metabolizable energy intakes were adjusted to
      .20 Mcal/kg of BW.75 for both dietary treatments. Lambs were weighed and feed
      intakes adjusted weekly. Lambs were bled via jugular venipuncture on d 28, 56,
      and 84 and lambs were slaughtered after they had been fed the diets for 90 d.
      Plasma concentrations of total cholesterol, high-density lipoprotein cholesterol,
      triglycerides, and nonesterified fatty acids were increased (P = .01) by feeding
      PO. Lambs fed PO were fatter than lambs fed NPO, as indicated by greater
      subcutaneous fat thickness and kidney and pelvic fat. Initial plasma cholesterol
      concentration had little effect on any of the parameters measured. Lambs fed PO
      had fatter carcasses than lambs fed NPO at calculated equalized ME intakes, which
      indicates that energy deposition is more efficient in palm oil-supplemented
      diets.

PMID- 8157518
TI  - Effect of biological type of cattle on the incidence of the dark, firm, and dry
      condition in the longissimus muscle.
AB  - The objectives of this experiment were to characterize longissimus muscle color,
      texture, and firmness for beef carcasses of diverse biological types and to
      determine the genetic parameters of lean color, texture, and firmness. The
      carcasses (n = 3,641) used in this experiment were from steers produced by mating
      Angus, Brahman, Braunvieh, Charolais, Chianina, Galloway, Gelbvieh, Hereford,
      Jersey, Limousin, Longhorn, Maine Anjou, Nellore, Piedmontese, Pinzgauer, Red
      Poll, Sahiwal, Salers, Shorthorn, Simmental, South Devon, and Tarentaise sires to
      Hereford and Angus dams. Steers were fed a corn-corn silage diet from weaning
      until slaughter at 356 to 575 d of age. Steers were slaughtered at commercial
      packing plants and longissimus muscle color, texture, and firmness were scored by
      trained carcass evaluators. Sire line least squares means for lean color,
      texture, and firmness ranged approximately one unit on a 7-point scale. Chianina
      crosses had darker-colored lean than all breed groups except Tarentaise and
      Simmental crosses (P < .05). Moreover, a higher percentage (P < .05) of Chianina
      crosses than of all other breed groups had unacceptably dark-colored ("dark red"
      or darker) lean. Bos indicus sire lines were not different from Bos taurus sire
      lines in frequency of carcasses with unacceptably dark-colored lean. However, Bos
      indicus crosses were more likely to be scored "very light cherry-red." Lean color
      and texture were lowly heritable, whereas lean firmness was moderately heritable.
      Thus, this experiment demonstrated that there is genetic variation in the
      incidence of the DFD condition; however, genetic variation was small relative to
      environmental variation.

PMID- 8157519
TI  - Prediction of net energy value of feeds for growing pigs.
AB  - Digestible (DE), metabolizable (ME), and net (NE) energy values of 61 diets were
      measured in 45-kg growing Large White boars. Net energy was calculated as energy
      retained at an average ME intake equivalent to 540 kcal/kg BW.60 plus fasting
      heat production estimated from data of the present experiment as 179 kcal/kg
      BW.60. Retained energy was measured as the difference between ME intake and heat
      production obtained in respiration chambers. The amounts of DE digested before
      the end of the ileum (DEi) and in the hindgut (DEh) were also measured for each
      diet. Regression equations for predicting dietary NE content from digestible
      nutrient levels or from DE or ME and chemical characteristics or from chemical
      composition only were calculated. Efficiencies of utilization of ME for NE (k, %)
      were also obtained. The mean k value for the 61 diets was 74% (range: 69 to 77).
      Digestible nutrients were used differently for NE: k values varied from
      approximately 60% for digestible CP or digestible cell wall fractions to 82% for
      starch and 90% for digestible ether extract. Accordingly, k for ME associated
      with DEh was lower than ME from DEi (58 vs 76%). Equations for predicting NE
      content are proposed. Their applicability, the comparison with other available NE
      prediction equations, and the effects of energy system on diet formulation are
      discussed.

PMID- 8157520
TI  - In vivo estimation of body composition of mature gilts using live weight, backfat
      thickness, and deuterium oxide.
AB  - Thirty-seven Duroc x (Yorkshire x Landrace) (DYL) and 21 Yorkshire x Landrace
      (YL) gilts were used to develop equations that predict body composition of
      replacement-age breeding swine. Before slaughter, gilts were weighed,
      ultrasonically scanned for 10th rib backfat thickness, and infused with D2O (.25
      g/kg live weight). The D2O space (kilograms) was calculated from body water D2O
      concentration determined at equilibrium (150 and 210 min after infusion).
      Regression models predicting empty body (Eb) components for DYL and YL groups
      were fitted using all possible variable combinations (D2O space, live weight,
      and[or] backfat depth). Variables selected in best-fit models for Eb water,
      protein, fat, and ash for data from DYL gilts differed from variables selected
      from data from YL gilts. Average prediction errors (kilograms; [predicted
      residual sum of squares divided by n]1/2) of best-fit equations were 2.37, 2.03
      (Eb weight), 2.36, 1.66 (Eb water), 1.07, .47 (Eb protein), and 2.76, 2.89 (Eb
      fat) for DYL and YL data sets, respectively. Cross-validation by applying DYL
      equations to YL data, and vice versa, resulted in larger prediction errors.
      Likewise, larger errors were obtained when equations published elsewhere were
      applied to DYL and YL data sets. No cited source provided a set of equations that
      consistently minimized prediction errors of all Eb components of both DYL and YL
      gilts. Results indicate that prediction equations using D2O space, live weight,
      and(or) backfat thickness are accurate in estimating body composition only in
      animals physiologically resemble the population in which the equations were
      derived.

PMID- 8157521
TI  - The effects of diets formulated on an ideal protein basis on growth performance,
      carcass characteristics, and thermal balance of finishing gilts housed in a hot,
      diurnal environment.
AB  - Forty-eight finishing gilts (initial BW = 70.6 +/- .95 kg) were randomly assigned
      to one of eight experimental treatments in a 2 x 2 x 2 factorial arrangement with
      main effects including dietary lysine (.60 vs 1.00%), source of amino acid
      fortification (intact protein vs synthetic amino acids formulated on an ideal
      protein basis), and environmental temperature (thermoneutral [TN]: 20 degrees C
      vs hot, diurnal [HD]: 27.7 to 35 degrees C). The ideal protein diets were
      formulated by using corn and soybean meal to meet the fifth-limiting amino acid;
      synthetic lysine, threonine, tryptophan, methionine, or isoleucine were added to
      meet the gilts' estimated requirements. The ratios of other total amino acids
      relative to lysine were as follows: threonine, 66%; tryptophan, 17%; methionine
      and cystine, 56%; and isoleucine, 63%. Average daily gain, ADFI, and feed
      efficiency (G/F) were similar for gilts fed the intact and those fed the ideal
      proteins diets (P > .10). Increasing dietary lysine improved d 0 to 14 ADG (P <
      .01), but no differences were observed for the overall experiment. Gilts in the
      HD environment ate less feed and had lower ADG than gilts in the TN environment
      (P < .01). A temperature x lysine interaction was observed (P < .02) for G/F.
      Increasing dietary lysine had no effect on G/F of gilts in the TN environment but
      improved G/F of gilts in the HD environment. Gilts fed the intact protein diets
      had higher (P < .01) N intake and plasma urea concentrations. Gilts fed the ideal
      protein diets had lower (P < .05) plasma essential amino acids, with the
      exception of lysine. Carcass protein and lipid contents were improved (P < .01)
      for gilts in the HD environment and for those fed 1.00% lysine. Backfat thickness
      and longissimus muscle area (P < .01) were improved and lipid accretion rate
      tended to decrease (P < .08) in gilts fed 1.00% lysine. The source of amino acid
      fortification did not influence carcass characteristics (P > .10). Rectal, skin,
      and ear temperatures were higher for gilts in the HD environment (P < .05).
      Metabolic heat production was elevated by feeding gilts the ideal protein diets
      (P < .03). In conclusion, increased dietary lysine improved G/F and carcass
      leanness in gilts to a greater extent in HD than in TN environments. However, no
      improvements in growth performance or carcass traits resulted from feeding ideal
      protein diets.

PMID- 8157522
TI  - The effect of supplemental lysine and threonine on growth and development of
      yearling horses.
AB  - Thirty-nine Thoroughbred and Quarter Horse yearlings were used in two 112-d
      experiments to determine the effect of lysine and threonine supplementation on
      growth and development. Yearlings were individually fed three dietary treatments
      that consisted of a pelleted concentrate containing corn, oats, and soybean meal
      fed to appetite twice daily and Coastal bermuda grass hay group-fed at a rate of
      1 kg/100 kg BW. Three concentrates were tested: (A) basal, (B) basal plus .2%
      lysine, and (C) basal plus .2% lysine, and .1% threonine. Feed intake, weight,
      withers height, girth, hip height, body length, and hoof growth (Exp. 1) were
      recorded every 28 d, and initial and final radiographs taken for estimating bone
      mineral content. Final croup fat thickness was measured ultrasonically in Exp. 1,
      and initial and final croup fat measured in Exp. 2. Blood samples were taken
      every 28 d for determination of serum urea N and protein in Exp. 2. Average daily
      feed intake (as-fed) was 8.8 +/- .14, 9.0 +/- .13, and 9.2 +/- .13 kg (P < .09),
      ADG was .57 +/- .02, .64 +/- .02, and .67 +/- .02 kg/d (P < .02), and girth gain
      was 9.7 +/- .49, 10.1 +/- .46, and 11.3 +/- .47 cm (P < .05) for Treatments A, B,
      and C, respectively. Gain:feed ratios in Exp. 1 were 70.5, 70.8, and 75.5 g/kg (P
      > .10) and in Exp. 2 were 61.7, 70.8, and 70.2 g/kg (P < .10) for Treatments A,
      B, and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157523
TI  - Postpartum hypophagia in primiparous sows: I. Effects of gestation feeding level
      on feed intake, feeding behavior, and plasma metabolite concentrations during
      lactation.
AB  - To investigate the relationship between feeding level during gestation and
      voluntary feed intake, feeding behavior, and plasma metabolite levels during
      lactation, 18 crossbred, primiparous sows were assigned to two dietary
      treatments. From d 60 of gestation until farrowing, sows were fed either a
      standard level of feed (SL; 1.85 kg/d) or were allowed ad libitum (AL) access to
      feed. During a 28-d lactation all sows were allowed ad libitum access to feed.
      Eight SL and seven AL sows completed the experiment. Feed intake was measured
      daily during the final 40 d of gestation and throughout lactation. On d 105 of
      gestation and d 1, 7, 14, and 21 of lactation, feeding behavior was observed and
      blood samples were collected via indwelling catheters. Plasma was analyzed for
      nonesterified fatty acids (NEFA), insulin, glucose, and alpha-amino N. During
      gestation AL sows ate more feed than did SL sows. This increased intake was
      balanced by reduced feed intake during lactation, when AL sows ate less than SL
      sows (P < .001). The AL sows gained more weight during gestation (P < .001) and
      lost more weight during lactation (P < .005) than did the SL sows. Feed intake
      and weight change during gestation and lactation combined were not different
      between treatments (P = .85). During lactation, the AL sows ate fewer meals (P <
      .05) of a similar size than did the SL sows. During lactation, the area under the
      curve formed by plasma NEFA concentration was greater (P = .06) and that for
      insulin was less (P < .01) in AL than in SL sows.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8157524
TI  - Postpartum hypophagia in primiparous sows: II. Effects of feeding level during
      gestation and exogenous insulin on lactation feed intake, glucose tolerance, and
      epinephrine-stimulated release of nonesterified fatty acids and glucose.
AB  - The objectives of this experiment were 1) to determine whether allowing sows ad
      libitum access to feed from d 60 of gestation affects glucose tolerance and 2) to
      determine whether exogenous insulin increases feed intake by preventing
      mobilization of nonesterified fatty acids (NEFA). Sixty crossbred sows were
      assigned to one of two feeding regimens during gestation, either a standard level
      of feed (SL; 1.85 kg/d) or allowed ad libitum access to feed (AL). Sows also
      received an injection of either .75 IU of insulin/kg BW or saline daily during
      the first 7 d of lactation. Exogenous insulin increased ADFI at d 7 of lactation
      (P = .07) and increased total feed intake at d 7 and 14 of lactation (P = .09).
      Total feed intake during d 0 to 21 was not affected by insulin treatment.
      Compared with the SL sows, the AL sows were less tolerant of glucose infusion (1
      g of glucose/kg BW, i.v.) on d 1 of lactation (P < .01). Baseline and peak
      concentrations of insulin were not affected by feeding level during gestation (P
      = .4). Baseline and peak concentrations of NEFA were greater in AL sows than in
      SL sows (P < .001) and were not affected by insulin treatment (P = .39). Release
      of NEFA after epinephrine stimulation was greater in AL sows than in SL sows (P <
      .05). The data indicate that the reduced feed intake during lactation exhibited
      by sows that are overfed during gestation may be caused by insulin resistance.
      Exogenous insulin seems to increase feed intake by reducing plasma glucose rather
      than be affecting plasma NEFA.

PMID- 8157525
TI  - Blood metabolite and regulatory hormone concentrations and response to metabolic
      challenges during the infusion of mimosine and 2,3-dihydroxypyridine in alpine
      goats.
AB  - Sixteen Alpine wethers (average BW 35 +/- 2 kg) were used to evaluate the effect
      of continuous 48-h intravenous infusions of saline (CON), mimosine (MIM; 200
      mg.kg.75.d-1), 2-hydroxy-3(1H)-pyridine (2,3-DHP; 200 mg.kg.75.d-1, or MIM+2,3
      DHP (100 mg of MIM plus 100 mg of 2,3-DHP-kg.75.d-1) on hepatic function and
      selected blood metabolite and circulating hormone concentrations. Neither MIM nor
      2,3-DHP affected plasma ammonia N, glucose, cortisol, or insulin concentrations
      over time (P > .10). Jugular plasma total protein concentration was greater in
      the MIM group (P < .07). Plasma triiodothyronine (P < .01) and thyroxine (P <
      .08) concentrations were higher in the goats receiving the MIM, 2,3-DHP, and
      MIM+2,3-DHP infusions than in the goats receiving the CON infusion. Plasma urea N
      concentration was decreased by MIM (P < .10) and MIM+2,3-DHP (P < .03) compared
      with the CON infusion. A Propionate Load Test was conducted at 24 to 28 h into
      the infusion to assess the toxins' effects on the liver's ability to increase
      circulating glucose concentrations in the presence of elevated propionate levels.
      The results indicated that neither 2,3-DHP nor MIM reduced the liver's ability to
      respond to a bolus dose of propionate (P > .10). Following a Urea Load Test,
      circulating ammonia N and glucose concentrations in the MIM, 2,3-DHP, and MIM+2,3
      DHP treatments had lower peak values than that in the CON treatment (P <
      .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157526
TI  - Effects of dietary insulin-like growth factor I on growth and insulin-like growth
      factor receptors in neonatal calf intestine.
AB  - Colostrum is rich in IGF-I and IGF-II, and the dietary effects of recombinant
      human (rh)IGF-I on the newborn are of interest. The objective of this study was
      to examine the effects of dietary rhIGF-I on intestinal tissue growth and
      populations of IGF receptors. Twenty-three male diary calves were fed one of
      three experimental diets: 1) milk replacer plus isolated colostrum-derived
      globulins (MR-), 2) same as 1 plus 750 ng of rhIGF-I/mL (MR+), or 3) pooled cow
      colostrum (COL). After the first four feedings, all calves received milk replacer
      without additional globulins; calves fed the MR+ diet continued to receive the
      addition of 750 ng of rhIGF-I/mL until the experiment ended at 7 d after birth.
      Calves were killed and intestinal tissue was collected for in vitro [3H]thymidine
      incorporation studies. Incorporation differed among intestinal regions (duodenum,
      jejunum, and ileum). The MR+ calves had greater (P < .01) [3H]thymidine
      incorporation per unit of DNA than either the COL or MR- calves (31.8 vs 18.6 and
      11.5 x 10(3) dpm/microgram of DNA, respectively). Competitive binding analysis
      indicated the presence of specific type 1 and type 2 intestinal IGF receptors.
      The IGF-I was more potent than IGF-II and insulin at inhibiting [125I]rhIGF-I
      binding (ED50 was 1.84, 9.17, and 1.91 ng/mL, respectively). The IGF-II was the
      only ligand capable of inhibiting [125I]rhIGF-II binding (ED50 was .30
      nmol/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157527
TI  - Effect of free amino acids and vitamins on cleavage and developmental rate of
      bovine zygotes in vitro.
AB  - Due to the complicated media used for culturing bovine embryos, most of the
      nutrient requirements are unknown. Recently, we developed a simple, serum-free
      medium (CR1) that allows bovine embryos to develop in vitro. Therefore, our
      objective was to determine whether development of bovine embryos would be
      improved by the addition of free amino acids and vitamins to CR1. Oocytes were
      recovered from slaughterhouse ovaries and matured 22 +/- 2 h, following which the
      oocytes were randomly allotted to treatment. The experiment was a randomized
      block design with a 2 x 5 factorial treatment structure. The oocytes were
      fertilized with or without cumulus cells intact. The five fertilization media
      were 1) Control (CR1 +/- 10 micrograms/mL of phenol red); 2) control + basal
      medium Eagle (BME) essential amino acids (EAA) + minimum essential medium (MEM)
      nonessential amino acids (NEA) + MEM vitamins (VIT); 3) control + EAA + NEA; 4)
      control + EAA + VIT; and 5) control + NEA + VIT. Cleavage rate was greater (P <
      .001) when cumulus cells remained on the oocytes during fertilization (51.7 vs
      73.2% without and with cumulus cells, respectively). The frequency of blastocysts
      was increased (P < .001) when EAA or NEA were added to CR1; however, adding VIT
      had no effect or tended (P = .12) to decrease the frequency of embryos attaining
      the blastocyst stage. This experiment demonstrates that development of bovine
      embryos in vitro can be improved by the addition of free amino acids to a simple
      medium. Contrary to work in rodents, the mixture of vitamins in MEM was not
      beneficial for bovine embryos.

PMID- 8157528
TI  - Responses of bovine lymphocytes to heat shock as modified by breed and
      antioxidant status.
AB  - We tested whether resistance of lymphocytes to heat stress is modified by breed,
      intracellular glutathione content, and extracellular antioxidants. In the first
      experiment, lymphocytes from Angus (Bos taurus, non-heat-tolerant), Brahman (B.
      indicus, heat-tolerant), and Senepol (B. taurus, heat-tolerant) heifers (12
      heifers per breed) were cultured at 45 degrees C for 3 h to evaluate thermal
      killing, at 42 degrees C for 12 h in a 60-h phytohemagglutinin-induced
      proliferation test, and at 42 degrees C for 1 h to measure induction of heat
      shock protein 70 (HSP70). Killing at 45 degrees C was affected by breed x
      temperature (P < .01); the decrease in viability caused by a temperature of 45
      degrees C was greater for Angus than for Brahman or Senepol. For
      phytohemagglutinin-stimulated lymphocytes, heating to 42 degrees C reduced
      [3H]thymidine incorporation equally for all breeds. Viability at the end of
      culture was affected (P < .001) by a breed x temperature interaction because the
      decrease in viability caused by culture at 42 degrees C was greatest for
      lymphocytes from Angus heifers. Heat shock for 1 h at 42 degrees C caused a two-
      to threefold increase in intracellular concentrations of HSP70, but there was no
      interaction of temperature with breed. In another experiment (with lymphocytes
      harvested from three Holstein cows), buthionine sulfoximine, a glutathione
      synthesis inhibitor, inhibited (P < .01) proliferation of phytohemagglutinin
      stimulated lymphocytes at 38.5 and 42 degrees C. Addition of the antioxidants
      glutathione or thioredoxin to culture did not reduce the effects of heating to 42
      degrees C on proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157529
TI  - Growth and reproductive development in Brahman bulls fed diets containing
      gossypol.
AB  - To determine the effect of gossypol on growth and reproductive development,
      Brahman bulls (n = 30) were fed diets containing gossypol (6 or 60 mg.kg BW-1.d
      1) or a diet free of gossypol from weaning through puberty. Diets contained
      cottonseed meal (CSM), whole cottonseed (WCS), or soybean meal (SBM) as the major
      sources of dietary CP. Diets were formulated to provide similar NEg for medium
      framed bulls to gain .9 kg/d. Measurements of BW and scrotal circumference were
      obtained at 28-d intervals, and beginning at 10 mo of age electroejaculates were
      collected at 14-d intervals. By 196 d on feed, bulls fed WCS had gained less (P <
      .05) BW and tended (P < .10) to have lower gain/feed than bulls fed CSM. When
      spermatozoa were first detected in an ejaculate, bulls fed CSM tended (P < .10)
      to be younger than bulls fed WCS (357 vs 386 d; SBM = 380 d); bulls fed SBM were
      heavier (P < .05) than bulls fed gossypol (333 vs 310 kg), but they had similar
      scrotal circumferences. Bulls fed WCS reached puberty at an older (P < .05) age
      (613 d) than bulls fed CSM (528 d; SBM = 550 d) but had similar BW and scrotal
      circumferences. Electroejaculated semen quality and quantity did not differ (P >
      .10) between treatments at puberty. Seminiferous tubule diameters did not differ
      (P > .10) among treatments, but bulls fed diets that contained gossypol had
      larger (P < .01) lumenal diameters, smaller (P < .01) germinal epithelium
      thickness, and fewer (P < .01) germ cell layers than bulls fed SBM
      diets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157530
TI  - Effects of administration of human chorionic gonadotropin or progesterone before
      maternal recognition of pregnancy on blastocyst development and pregnancy in
      sheep.
AB  - A series of four experiments with 258 ewes was conducted to determine whether
      blastocyst size could be altered before normal luteolysis and, if so, how this
      affected fertility. In Exp. 1 and 2, nonmated and mated ewes, respectively, were
      treated with hCG (100 IU), progesterone (12 mg), or vehicle on d 11.5 (d 0 =
      onset of estrus). In Exp. 3 and 4, field trials were conducted to compare the
      effects of either hCG or progesterone treatment on d 11.5 on subsequent pregnancy
      rates. In Exp. 1, hCG transiently increased (P < .01) concentrations of
      progesterone and estradiol in plasma, whereas progesterone treatment increased
      only plasma progesterone. Neither hCG nor progesterone affected the duration of
      the estrous cycle. In Exp. 2, d-13 blastocysts were longer (3.5 +/- 1.6 vs .8 +/-
      .5 cm; Mean +/- SE; P < .05), and concentrations of protein and interferon tau
      (IFN tau) in uterine flushings were greater (10.7 vs 1.2 micrograms; P < .05) in
      hCG than in vehicle-treated ewes. Progesterone treatment did not affect
      blastocyst development. In Exp. 3, pregnancy rates tended to be greater (P < .10)
      in ewes given hCG than in those given vehicle (44/47; 94% vs 40/48; 83%);
      however, administration of progesterone in Exp. 4 had no effect on pregnancy
      rates (P < .14; 41/45; 91% vs 37/46; 80%; control ewes). These results indicate
      that treatment with hCG on d 11.5 stimulated uterine secretions and conceptus
      growth sufficiently to influence pregnancy rates.

PMID- 8157531
TI  - Changes in peripheral concentrations of 13,14-dihydro-15-keto-prostaglandin F2
      alpha induced by progesterone in swine.
AB  - This experiment was designed to examine the effects of progesterone on endogenous
      and oxytocin-induced secretion of prostaglandin F2 alpha (PGF2 alpha) in sows.
      Peripheral concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were used as
      an indirect measure of uterine PGF2 alpha secretion. Eight sows received twice
      daily injections of progesterone (160 mg/injection) on d 1 to 5 after estrus.
      Another eight sows received comparable injections of a corn oil injection
      vehicle. Each sow then received i.v. injections of oxytocin (30 IU) on d 10, 12,
      and 15 after estrus. Concentrations of PGFM were determined in jugular venous
      blood samples collected at -60, -45, -30, -15, 0, 2, 5, 10, 15, 30, 45, 60, 90,
      and 120 min after each oxytocin injection. The mean concentrations of PGFM in
      samples collected before injection of oxytocin (baseline), the magnitude of the
      PGFM response to oxytocin, and the area under the PGFM response curve (AUC) were
      calculated for the three oxytocin challenges administered to each sow. Baseline,
      magnitude, and AUC were low on d 10 after estrus and similar for the two
      treatment groups. On d 12 baseline, magnitude, and AUC remained low in the
      control sows; however, all three response variables increased in sows that
      received progesterone. By d 15, all three variables were high and similar in both
      treatment groups. In conclusion, progesterone, administered early in the estrous
      cycle, seems to promote premature secretion of PGF2 alpha as indicated by the
      high basal concentrations of PGFM observed before injection of oxytocin on d
      12.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157532
TI  - Effects of phenolic monoamines on release of luteinizing hormone stimulated by
      gonadotropin-releasing hormone and on plasma adrenocorticotropic hormone,
      norepinephrine, and cortisol concentrations in wethers.
AB  - Eighteen Suffolk and Suffolk x Hampshire wethers (56.3 +/- 1.3 kg) were used to
      determine the effects of naturally occurring amines, N-methyl-beta-phenethylamine
      (NMP) and tyramine (T), on plasma cortisol, norepinephrine (NE), ACTH, and GnRH
      stimulated LH concentrations. In each experiment, wethers were assigned randomly
      to treatments with six replicates/treatment. In Exp. 1, treatments consisted of
      saline, 2 mg of NMP/kg BW (NMP2), or 4 mg of NMP/kg BW (NMP4). In Exp. 2,
      treatments consisted of saline, 4 mg of NMP/kg BW (N), or 2 mg of NMP + 4 mg of
      T/kg BW (NT). All treatments were given via indwelling jugular catheters in
      single doses of 2 mL. In Exp. 1, no effects of time after treatment on response
      were detected. The NMP2 wethers had lower cortisol and LH peak amplitudes (PKAMP)
      than other wethers (P < .03 and .05, respectively). Time to peak (PKT)
      concentration of NE was significantly shorter in NMP4-treated wethers (P < .004).
      In Exp. 2, significant interactions between time and treatment were detected for
      cortisol, NE, and LH. Cortisol and NE concentrations were increased (P < .0001
      and P < .03, respectively) in N- and NT-treated wethers compared with controls,
      whereas LH was reduced (P < .003). The N and NT treatments increased cortisol
      PKT, peak height (PKHT), and PKAMP above that of controls (P < .02, < .006, and <
      .02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157533
TI  - Performance and nutrient metabolism by nursing calves supplemented with limited
      or unlimited corn or soyhulls.
AB  - Five-month-old Angus x Hereford reciprocal crossbred nursing steer calves on
      fescue pasture were used to determine the effects of 1) limiting supplemental
      feed intake and 2) soyhulls and corn as sources of supplemental (creep) feed in
      an 84-d study. The treatments were 1) control (no creep feed), 2) limited intake
      of corn (1 kg/d), 3) unlimited intake of corn, 4) limited intake of soyhulls (1
      kg/d), and 5) unlimited intake of soyhulls. Before weaning, there were no
      differences in supplemental feed efficiency ([supplemented gain--control
      gain]/supplement intake) or calf gain between corn or soyhulls. Calf gain before
      weaning increased linearly (P < .05) as intake of creep feed increased, but
      supplemental feed efficiency did not differ between limited and unlimited
      supplements. Feedlot performance by the calves was not affected by any of the
      previous treatments. Calves that consumed an unlimited level of creep feed had
      greater (P < .05) quality grades than the control group that did not consume
      creep feed, but no other carcass traits were influenced by treatment. In a
      metabolism study, fescue DM intake decreased linearly (P < .001) with increasing
      levels of creep feed, whereas milk DM intake was not affected by level of creep
      feed. Digestible DM intake increased linearly (P < .001) with increasing intake
      of creep feed. No differences (P < .18) were observed in digestible DM intake as
      a result of creep feed source. Apparent total tract DM digestibility increased (P
      < .05) with increasing level of creep feed intake but did not differ between
      sources.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157534
TI  - Steers grazing intermediate wheatgrass at various stages of maturity: effects on
      nutrient quality, forage intake, digesta kinetics, ruminal fermentation, and
      serum hormones and metabolites.
AB  - Six ruminally cannulated Holstein steers (average BW of 495 +/- 5 kg) grazed a 32
      ha, nonirrigated, intermediate wheatgrass (Thinopyrum intermedium Host) pasture
      from April 10 through December 7. Sample collections were conducted in May, June,
      September, and November 1989. Total masticate N decreased (P < .05) and bound N
      increased (P < .05) with advancing forage maturity. Masticate in vitro OM
      disappearance was lower (P < .05) in November (40.5%) than in May (62.0%).
      Organic matter intake (grams/kilogram of BW) decreased (P < .05) at each sampling
      date (May = 35.7, June = 26.8, September = 20.0, November = 14.9).
      Correspondingly, particulate passage rate decreased and gastrointestinal mean
      retention time increased (P < .05) with advancing forage maturity. Extent and
      rate of NDF digestion were greater (P < .05) during May and June than during
      September and November. Ruminal NH3 N and total VFA concentrations were greater
      (P < .05) during May and June than during September and November. Advancing
      forage maturity did not alter (P > .10) serum growth hormone concentrations;
      however, nonesterified fatty acid concentrations were greater (P < .05) during
      September and November than during May and June. Serum insulin-like growth factor
      I decreased (P < .05) with advancing forage maturity. Seasonal changes in forage
      intake and ruminal fermentation suggest that animal performance might be
      increased if supplemental energy is provided early in the growing season of
      intermediate wheatgrass; however, supplemental protein would likely be needed as
      wheatgrass matures.

PMID- 8157535
TI  - Effect of feeding regimen on concentration of free endotoxin in ruminal fluid of
      cattle.
AB  - The influence of concentrate diets on endotoxin concentration in sterile filtrate
      of ruminal fluid was assessed in ruminally fistulated Jersey cows. Three cows
      underwent a change in diet from hay to a diet containing 3.0 kg and 14 d later
      6.0 kg of a 12% CP concentrate. The cows had free access to water and a mineral
      stone. A modified Limulus Amoebocyte Lysate technique was used for the endotoxin
      analyses. The endotoxin concentration in the ruminal fluid of cows fed on hay
      were 148 +/- 84 and 118 +/- 50 endotoxin units (EU)/mL (mean +/- SD) on two
      separate days and increased from the 2nd d of supplementation with 3.0 kg of
      concentrate to 408 +/- 198 EU/mL on d 5. When the cows were fed 6.0 kg of
      concentrate, the endotoxin concentrations increased to 1,599 +/- 944 EU/mL. To
      assess the influence on the ruminal endotoxin concentration of an adaptation of
      the ruminal environment to concentrate before hyperalimentation, four ruminally
      fistulated Jersey cows previously fed either hay or a high-concentrate diet for 1
      mo were hyperalimented with 60 to 70 g of barley per kilogram BW. A relative
      increase in ruminal endotoxin concentration was determined only in the two cows
      previously fed concentrates. The results show that high-concentrate diets do not
      consistently relate to increases of ruminal endotoxin concentrations.

PMID- 8157536
TI  - Effects of a supply of raw or extruded white lupin seeds on protein digestion and
      amino acid absorption in dairy cows.
AB  - Four cannulated, lactating cows were used to determine the effects of extruding
      white lupin seeds (WLS) on intraruminal CP degradation and absorption of AA from
      the small intestine. Raw lupin seeds (RWLS) and extruded lupin seeds (EWLS) were
      fed in diets containing 15.5% CP and composed of 22.4% WLS, 55.9% corn silage,
      10.1% maize grain, and 10.6% Italian ryegrass on a DM basis; WLS provided
      approximately 50% of the total dietary CP. Spot samples of digesta were collected
      from the proximal duodenum and terminal ileum during 72 h. Chromium EDTA, YbCl3,
      and purines were used as liquid, particulate, and bacterial markers,
      respectively. Because of the extensive ruminal degradation of dietary N with the
      RWLS diet compared with the EWLS diet (64.2 vs 38.8%), less total AA flowed to
      the duodenum (1,748 vs 2,347 g/d), and because of the decrease of availability
      (67.2 vs 79.0% of entering), absorption from the small intestine was lowest with
      this diet (1,175 vs 1,855 g/d). The apparent digestion of individual AA in the
      small intestine (percentage entering) ranged from 46.5 to 88.4 when cows consumed
      RWLS and from 58.9 to 94.4 when they were fed the EWLS diet. Among the diets,
      apparent absorption of histidine, lysine, glycine, and serine were higher than
      those of other AA; also, valine, alanine, and proline showed intestinal
      absorptions that were somewhat lower than those of the remainder of the AA.

PMID- 8157537
TI  - Serum neutralizing antibodies against Fusobacterium necrophorum leukotoxin in
      cattle with experimentally induced or naturally developed hepatic abscesses.
AB  - The relationship between serum-neutralizing antibody against Fusobacterium
      necrophorum leukotoxin and hepatic abscesses was investigated in cattle fed diets
      supplemented with or without tylosin. Sixteen cattle (eight each in tylosin and
      in control groups) were inoculated intraportally with F. necrophorum.
      Ultrasonographic scanning showed that all control animals developed hepatic
      abscesses after inoculation. In the tylosin group, two animals were free of
      abscess by d 7 and one was free by d 14. Leukotoxin-neutralizing antibody titers
      were low on d 0, but increased (P < .05) markedly after intraportal inoculation
      in both groups. In a second study, blood was collected at the time of slaughter
      from 141 feedlot cattle (36 fed diets with tylosin and 105 fed diets without
      tylosin), and livers were examined for presence or severity of hepatic abscesses
      at slaughter. The incidences of hepatic abscesses were 32% in the control group
      and 6% in the tylosin group. Antibody was detected in all animals; however,
      antibody titers were greater (P < .05) in cattle with abscessed liver than those
      without, and greater (P < .01) in the nontylosin than in the tylosin group.
      Abscess score and antibody titer were correlated (r = .34; P < .0001). We
      conclude that F. necrophorum leukotoxin is highly antigenic and that anti
      leukotoxin antibody titer is related to the severity of hepatic abscesses.

PMID- 8157538
TI  - Effects of substituting feather meal for soybean meal on ruminal fiber
      fermentation and lamb and wool growth.
AB  - Our objective was to evaluate the effects of substituting feather meal (FM) for
      soybean meal (SBM) on ruminal fiber fermentation, lamb gain, blood metabolite
      profiles, and wool growth. A SBM supplement was formulated, and FM replaced
      either 33% (33FM), 66% (66FM), or 100% (FMS) of the SBM protein. Four ruminally
      cannulated wethers were used in a 4 x 4 Latin square design to study in situ
      ruminal digestion. Wethers were limit-fed barley straw and fed the supplements
      once daily. Ruminal NH3 N concentrations reflected a sampling time x protein
      source interaction (P < .01). Within sampling times, ruminal NH3 N concentrations
      decreased linearly (P < .05) as FM replaced soybean meal. Cubic (0 h; P < .10)
      and quadratic (24 h; P < .05) responses also were noted for ruminal NH3 N
      concentration. Substitution of FM for SBM had no effect (P > .10) on rate and
      extent of straw NDF disappearance. A 56-d feeding trial was conducted using 28
      wether lambs (n = 7 per treatment; initial BW 32.3 kg). Wethers were individually
      fed chopped barley straw and one of the four supplements described previously.
      Linear increases (P < .05) in BW gain and serum total protein concentration were
      observed as FM replaced SBM. Wool fiber diameter and sulfur content did not
      differ (P > .10) among treatments. These data suggest that FM can be substituted
      for SBM in protein supplements fed to sheep consuming low-quality roughages at a
      maintenance level of ME intake.

PMID- 8157540
TI  - Animal well-being in pharmacology and toxicology research.
AB  - The primary objective of this paper is to heighten the awareness of animal
      welfare issues among animal scientists. Emphasis is placed on issues relating to
      pharmacology and toxicology research with animals. Use of both laboratory animals
      and farm animals is addressed; major consideration is given to domestic
      livestock. Animal welfare issues are complex and have philosophical, ethical,
      legal, societal, scientific, and biological bases and implications. There is
      substantial diversity in public opinion and perception regarding use of animals
      in research, including the belief among some people that use of animals in
      research should be eliminated altogether. Increasingly, public opinion is tending
      toward expectations of alternatives to the use of live animals for research. From
      an animal scientist's viewpoint, although the availability and development of
      viable alternatives are increasing, live animal research in pharmacology and
      toxicology currently has no acceptable alternative, in many cases because of the
      complex interactions involved in whole-animal (biological) systems. Compliance
      with federal, state, and local laws, regulations, and policies requires animal
      scientists to use only appropriate species for research, use the minimum number
      of animals needed, minimize pain and discomfort, and consider alternatives to the
      use of live animals. In summary, it is essential that animal scientists be
      advocates of animal well-being and adhere to appropriate guidelines for animal
      care and use when conducting research with animals.

PMID- 8157539
TI  - Effects of anabolic steroids on nitrogen metabolism and growth of steers fed corn
      silage and corn-based diets supplemented with urea or combinations of soybean
      meal and feathermeal.
AB  - The objectives of these experiments were to examine whether N retention and
      feedlot performance by steers administered estradiol 17-beta (E2) alone
      (metabolism study) or in combination with trenbolone acetate (TAB; feedlot study)
      could be enhanced by increasing dietary ruminal escape protein. For the
      metabolism study, 16 Angus steers (average weight = 308 +/- 5 kg) were used in a
      randomized block design experiment having a 2 x 4 factorial arrangement of
      treatments. Main factors were E2 administration and supplemental CP source.
      Steers were fed diets based on corn silage and corn (60:30 DM basis) and were
      supplemented with urea or three combinations of soybean meal (SBM) and
      feathermeal (Fth). Combinations and SBM and Fth (SBM:Fth) provided 75:25, 50:50,
      and 25:75 of supplemental CP on a N basis. Estradiol 17-beta increased (P < .05)
      N retention and decreased (P < .05) plasma urea N concentrations. Total tract N
      digestion decreased linearly (P < .05) as the proportion of Fth in the diet
      increased. However, N retention increased linearly (P < .05) with increased Fth.
      A CP source x E2 interaction (P < .05) was observed for N retention because
      retention increased linearly with increasing dietary Fth in cattle receiving E2
      but was unaffected (P > .05) in control steers. A growth study was conducted
      using 128 crossbred steers (400 +/- 19 kg) that received no implant or a
      combination of E2 (Synovex) and TBA (Finaplix-S). Steers were fed diets
      containing 75% high-moisture corn, 15% corn silage, and 10% supplement (DM basis)
      for 84 d (heavy replicate) or 124 d (light replicate).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8157541
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM209.

PMID- 8157542
TI  - Comparison of polymerase chain reaction and conventional culture for the
      detection of legionellas in hospital water samples.
AB  - A detection system for Legionella spp. based on the polymerase chain reaction
      (PCR) was used to assess the diagnostic value of PCR for the surveillance of
      contamination of man-made water systems by legionellas. A previously-published
      primer system was chosen to amplify a fragment of the 5S-ribosomal gene of
      Legionella spp. A total of 78 water samples from various sources were examined by
      PCR and culture on MWY Legionella selective agar. Fifty-seven of 78 water samples
      were positive by both test systems (73%), nine were positive by PCR only (11.5%),
      another nine were positive by culture but negative by PCR (11.5%), and three were
      negative by both techniques (3.8%). The PCR was inhibited when large amounts of
      rust were present in the samples. Culture failed to detect legionellas in samples
      that contained large numbers of other bacteria capable of overgrowing the
      legionellas. These results show that PCR is a rapid and sensitive technique for
      the detection of legionella contamination in water samples and that PCR and
      culture complement each other in monitoring of environmental water samples.

PMID- 8157543
TI  - Development of a diagnostic test for Yersinia pestis by the polymerase chain
      reaction.
AB  - A 501 bp caf1 gene fragment and a 443 bp of pla gene fragment carried by 100 kb
      (pFra) and 10 kb (pPst) species-specific extrachromosomal replicons,
      respectively, were used as targets to study the conditions under which DNA
      amplification by polymerase chain reaction (PCR) may be applied to detect and
      identify Yersinia pestis DNA in cell lysates of pure cultures and biological
      samples. The sensitivity limit of PCR with the crude cell lysates of Y. pestis EV
      was estimated as 10-50 cfu in reaction mixture. When target Y. pestis EV cells
      were mixed with fresh blood of white mice, which contained 0.4% potassium
      citrate, the PCR detection level varied from 400 to 100 cfu ml-1 of blood
      depending on the method used for preparing the sample. In our tests PCR was
      effective for the detection of yersinia in the blood of white laboratory mice
      experimentally infected with virulent Y. pestis KM638 strain. This method can be
      considered convenient for routine detection and identification of Y. pestis.

PMID- 8157544
TI  - Numerical taxonomy and identification of lactic acid bacteria from spoiled,
      vacuum-packaged vienna sausages.
AB  - Sixty-one lactic acid bacteria from spoiled vacuum-packaged vienna sausages and
      15 reference strains were tested for 72 phenotypic characteristics. An
      identification key and a computer data base, both specific for lactic acid
      bacteria from meat sources, were used for identification and the results were
      compared. There was a high correlation (86.9%) between the two procedures in the
      identification of strains to genus level. However, only a 54.8% correlation was
      obtained in identifying strains to the species level. With numerical taxonomy
      (Ssm matching coefficient with average linkage clustering) 60 strains were
      recovered in six clusters at the 89% similarity level. While most Leuconostoc
      strains clustered separately from the Lactobacillus strains, the identity of many
      leuconostocs was not clarified. The presence of a heterogeneous cluster
      containing typical and 'atypical' strains of the Lactobacillus sake/curvatus
      group and a separate homogeneous Lact. curvatus cluster was noted. Closer
      examination of the data suggested that the 'atypical' lactobacilli were all
      strains of Lact. sake.

PMID- 8157545
TI  - Ferric iron reduction-linked growth yields of Shewanella putrefaciens MR-1.
AB  - The anaerobic reduction of ferric citrate by Shewanella putrefaciens MR-1 cells
      was inhibited markedly by p-chloromercuriphenylsulphonate, moderately by
      potassium cyanide, and to a small extent by 2-heptyl-4-hydroxyquinolone-N-oxide.
      Iron reduction was accompanied by increases in total cellular protein, with
      values of 0.33-7.54 g cell protein produced per mol Fe(III) reduced. The growth
      yields were dependent upon the growth conditions of the inoculum and the initial
      concentration of Fe(III) citrate in the medium. Specifically, maximum growth
      yields were obtained when the inoculum was pregrown anaerobically and when the
      initial Fe(III) citrate concentrations were 5-10 mmol l-1. Lower growth yields
      were obtained with initial Fe(III) citrate concentrations of 20-30 mmol l-1,
      suggesting that cell growth was partially inhibited by higher concentrations of
      Fe(III) or Fe(II). Maximal growth yields were also observed early (6-24 h), after
      which continued increases in cell protein were minimal.

PMID- 8157546
TI  - Evaluation of a chromogenic chito-oligosaccharide analogue, p-nitrophenyl-beta-D
      N,N'-diacetylchitobiose, for the measurement of the chitinolytic activity of
      bacteria.
AB  - Three methods of quantifying chitinase activity were compared. The activities of
      crude chitinases of 10 bacterial isolates from different environments were
      estimated in terms of (1) the release of p-nitrophenol from the chromogenic chito
      oligosaccharide analogues, p-nitrophenyl-beta-D-N,N'-diacetylchitobiose, p
      nitrophenyl-N-acetyl-beta-D-glucosamine and p-nitrophenyl-beta-D-N,N',N"
      triacetylchitotriose, (2) the release of reducing sugars from chitin and (3) the
      formation of clearing zones on chitin agar. When crude chitinase from Bacillus
      pabuli was used the hydrolysis of p-nitrophenyl-beta-D-N,N'-diacetylchitobiose
      correlated well with the release of reducing sugars from chitin and the formation
      of clearing zones on chitin agar. However, when the activity of crude chitinases
      from the different bacterial isolates were compared no agreement was found
      between the hydrolysis of p-nitrophenyl-beta-D-N,N'-diacetylchitobiose and the
      release of reducing sugars from chitin or the formation of clearing zones on
      chitin agar. It was concluded that the assay with chromogenic p-nitrophenyl chito
      oligosaccharide analogues is not well suited for studies that compare the
      chitinase activity of different bacteria.

PMID- 8157547
TI  - Interactions between rumen bacterial strains during the degradation and
      utilization of the monosaccharides of barley straw cell-walls.
AB  - Pure cultures and pair-combinations of strains representative of the rumen
      cellulolytic species Ruminococcus flavefaciens, Fibrobacter succinogenes and
      Butyrivibrio fibrisolvens were grown on cell-wall materials from barley straw. Of
      the pure cultures, R. flavefaciens solubilized straw most rapidly. The presence
      of B. fibrisolvens, which was unable to degrade straw extensively in pure
      culture, increased the solubilization of dry matter by R. flavefaciens and the
      solubilization of cell-wall carbohydrates by both R. flavefaciens and F.
      succinogenes. During fermentation, both R. flavefaciens and F. succinogenes
      released bound glucose and free and bound arabinose and xylose into solution. The
      accumulation of these sugars, especially arabinose and xylose, was greatly
      reduced in co-cultures containing B. fibrisolvens, suggesting that significant
      interspecies cross feeding of the products of hemicellulose hydrolysis
      (particularly soluble bound xylose released by F. succinogenes) occurs during
      straw degradation by mixed cultures containing this species.

PMID- 8157548
TI  - Inhibition of enterotoxigenic Escherichia coli by the microflora of the porcine
      ileum, in an in vitro semicontinuous culture system.
AB  - An. in vitro fermentation system capable of maintaining at least part of the
      microbial population of the contents of the porcine ileum has been developed. The
      system was tested over the pH range 6.0-8.5, anaerobically and at dissolved
      oxygen concentrations within the ranges detected in the ileum of piglets at
      weaning (50 and 100 mumol l-1). The results demonstrated that changes in pH and
      dissolved oxygen within these ranges had relatively little effect on the total
      numbers of aerobic and anaerobic bacteria. Lactic acid bacteria, enumerated
      anaerobically, showed changes in viable counts in response to pH changes but were
      apparently unaffected by changes in dissolved oxygen, although the proportion of
      aerotolerant species within this group was increased at high concentrations of
      dissolved oxygen. The relative proportions of lactobacilli and coliforms were
      similar to those reported in vivo when dissolved oxygen was present at a
      concentration of 50 mumol l-1. Under these conditions the simulated population
      was consistently found to resist colonization by an enterotoxigenic Escherichia
      coli, of a serotype known to cause weaning scours in the piglet.

PMID- 8157549
TI  - Problems in susceptibility testings--findings of UK NEQAS for microbiology.
      United Kingdom National External Quality Assessment Scheme.

PMID- 8157550
TI  - The comparative pharmacokinetics and tissue penetration of single-dose
      ciprofloxacin 400 mg i.v. and 750 mg po.
AB  - The pharmacokinetics of ciprofloxacin following single doses of 400 mg i.v. and
      750 mg po were compared in six healthy volunteers. Concentrations of
      ciprofloxacin were measured in plasma, cantharides induced blister fluid and
      urine, by microbiological assay and high performance liquid chromatography
      (HPLC). Mean peak plasma concentration was 6.7 +/- 1.4 mg/L after i.v. and 3.9 +/
      1.7 mg/L after oral administration with mean elimination half-lives of 4.2 and
      4.0 h respectively. Mean area under the concentration versus time curve (AUC) was
      greater following oral administration (19.2 +/- 1.1 mg/L.h versus 14.2 +/- 1.1
      mg/L.h). Blister fluid peak concentrations following i.v. and oral administration
      were 2.6 +/- 1.3 mg/L and 2.28 +/- 1.2 mg/L respectively. The elimination half
      life from blister fluid was 4.1 +/- 1.1 h and the AUC 13.8 +/- 1.1 mg/L.h
      following i.v. administration compared with 4.6 +/- 1.5 h and 20.3 +/- 1.3 mg/L.h
      for the oral dose. A mean of 50.8% of i.v. administered drug and 39.6% or orally
      administered drug was excreted in urine in 24 h as measured by HPLC. The
      corresponding values by microbiological assay were greater, suggesting excretion
      of active metabolites. Both i.v. and oral doses produced levels in blister fluid
      concentration above the MICs for most Enterobacteriaceae, Pseudomonas aeruginosa,
      Haemophilus influenzae and Neisseria spp. at 12 h post dose. The pharmacokinetic
      data from inflammatory fluid indicate that ciprofloxacin 400 mg i.v. is more
      equivalent to 750 mg po than the plasma pharmacokinetic data suggest.

PMID- 8157551
TI  - Comparative crossover assessment of serum bactericidal activity and
      pharmacokinetics of ciprofloxacin and ofloxacin.
AB  - The study compared the pharmacokinetics and pharmacodynamics of ciprofloxacin and
      ofloxacin in 12 healthy male volunteers with normal renal function. Each
      volunteer received oral ciprofloxacin 500 mg, intravenous (i.v.) ciprofloxacin
      400 mg, oral ofloxacin 400 mg, or i.v. ofloxacin 400 mg in a randomized, double
      blind, crossover design with a one-week 'washout' period between doses. Mean peak
      serum concentrations were 4.48 and 5.44 mg/L for i.v. ciprofloxacin and
      ofloxacin, respectively. For the oral regimens, mean peak serum concentrations
      were 2.45 mg/L for ciprofloxacin and 4.44 mg/L for ofloxacin. Minimum
      bactericidal concentrations (MBC) and serum bactericidal activity (SBA) for each
      drug were measured against five strains of each of the following species:
      Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Pseudomonas
      aeruginosa, Acinetobacter anitratus, Haemophilus influenzae, Staphylococcus
      aureus, and Streptococcus pneumoniae, using the microdilution method of the
      National Committee for Clinical Laboratory Standards (NCCLS). Ciprofloxacin was
      more active in vitro than ofloxacin against the tested species of
      Enterobacteriaceae and P. aeruginosa, while ofloxacin was slightly more active
      against A. anitratus. MBCs for the two drugs were similar for H. influenzae and
      S. aureus. Oral and i.v. ciprofloxacin in the doses given resulted in nearly
      equivalent SBA. Similarly, oral and i.v. ofloxacin had nearly equivalent SBA. For
      the i.v. and oral regimens of both agents, peak SBA was > or = 2 throughout the
      12-hour test period against the Enterobacteriaceae and H. influenzae. At peak
      concentrations, both drugs had modest SBA against P. aeruginosa, A. anitratus,
      and S. aureus but little or no activity 8 and 12 h after dosing.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8157552
TI  - Linear pharmacokinetics of penciclovir following administration of single oral
      doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers.
AB  - Twenty healthy male volunteers received single oral doses of famciclovir (125-750
      mg), in a randomized, single-blind, crossover study. Plasma and urine
      concentrations of penciclovir and its 6-deoxy precursor, BRL 42359, were
      determined and penciclovir plasma concentration-time data submitted to model
      independent pharmacokinetic analysis. Peak plasma concentrations of penciclovir
      were obtained at median times of 0.5-0.75 h after dosing. The areas under the
      concentration versus time curves (AUC) and the peak penciclovir concentration
      (Cmax) increased linearly with dose of famciclovir. Time to Cmax, elimination
      half-life, urinary recovery and renal clearance of penciclovir did not change
      with increasing dose. Famciclovir was excreted via the kidneys as penciclovir
      (60%) and BRL 42359 (5%), respectively. Famciclovir was well tolerated by all
      subjects with a low incidence of adverse effects. In conclusion, penciclovir thus
      displays linear pharmacokinetics in the anticipated therapeutic dose range of
      famciclovir.

PMID- 8157553
TI  - Sputum and serum pharmacokinetics of loracarbef (LY163892) in patients with
      chronic bronchial sepsis.
AB  - Sputum and serum pharmacokinetics of loracarbef (LY163892) were performed in 19
      patients with purulent bronchiectasis. Nine of the patients received 200 mg twice
      daily and ten patients, 400 mg twice daily, for a total of 14 days. beta
      Lactamase activity was measurable in the lung secretions of all 19 patients at
      the start of therapy. Mean peak serum concentrations of 11.7 mg/L (S.E.M. 1.7)
      were recorded at 1 h after administration of 200 mg doses on day 2 of therapy and
      were 18.5 mg/L (S.E.M. 1.9) at 1.5 h in the 400 mg group. Loracarbef was shown to
      penetrate lung secretions even in the presence of beta-lactamase activity. Mean
      peak sputum concentrations were achieved between 2 and 4 h following dosing and
      were 0.2 mg/L (S.E.M. 0.05) in the 200 mg group and 0.4 mg/L (S.E.M. 0.08) in the
      400 mg group. On days 7 and 14 of therapy, sputum loracarbef concentrations were
      similar 4 h after the morning dose (0.23 mg/L following 200 mg; 0.35 mg/L after
      400 mg). These concentrations were approximately 2% of the peak serum
      concentration and penetration into lung secretions is similar to other beta
      lactams.

PMID- 8157554
TI  - In-vitro activity of FK-037, a new parenteral cephalosporin.

PMID- 8157556
TI  - Determination of 6-beta-bromopenicillanic acid (brobactam) in human serum by high
      performance liquid chromatography (HPLC) using solid phase extraction for sample
      preparation.

PMID- 8157555
TI  - Effect of rifampicin chemoprophylaxis on the aerobic bacterial flora of the
      oropharynx.

PMID- 8157557
TI  - The penetration of imipenem/cilastatin into ascitic fluid in patients with
      chronic liver disease.

PMID- 8157558
TI  - Sequential therapy with intravenous and oral cephalosporins.
AB  - The pharmacokinetic, economic and practical aspects of sequential therapy with iv
      and oral cephalosporins are reviewed. New broad spectrum oral cephalosporins,
      such as cefixime, cefpodoxime proxetil and cefetamet pivoxil achieve serum
      concentrations above the MICs for most Enterobacteriaceae for at least as long as
      for parenteral cefuroxime. Substantial cost reductions are possible with an early
      switch from iv to oral cephalosporins. The clinical studies that have been
      performed so far have important shortcomings. Well designed clinical studies are
      necessary to prove the feasibility of sequential therapy with cephalosporins for
      serious infections in hospitalized patients.

PMID- 8157559
TI  - P-nitrophenylglycerol in susceptibility media alters the MICs of antimicrobial
      agents for Pseudomonas aeruginosa.

PMID- 8157560
TI  - P-nitrophenylglycerol in susceptibility media alters the MICs of antimicrobial
      agents for Pseudomonas aeruginosa.

PMID- 8157561
TI  - Rapid killing of bacteria and inhibition of endotoxin activity.

PMID- 8157562
TI  - Zinc ions and medium-dependent susceptibility to beta-lactams in Xanthomonas
      maltophilia.

PMID- 8157563
TI  - L-627, a novel carbapenem: in-vitro activity against anaerobes.

PMID- 8157564
TI  - Susceptibility of pneumococci isolated from middle ear effusions to antimicrobial
      agents commonly used in otitis media.

PMID- 8157565
TI  - Quinolone resistant Haemophilus influenzae.

PMID- 8157566
TI  - Prevalence of fluoroquinolone resistance in clinical strains of Campylobacter
      jejuni isolated in Spain.

PMID- 8157567
TI  - Antibiotic resistance of Salmonella typhi in Bangladesh.

PMID- 8157568
TI  - Evaluation of a once-daily netilmicin regimen in the treatment of cystic
      fibrosis.

PMID- 8157569
TI  - Biliary excretion of ceftriaxone into non-stagnant and stagnant bile.

PMID- 8157570
TI  - Genetic structures associated with spread of the type Ia trimethoprim-resistant
      dihydrofolate reductase gene amongst Escherichia coli strains isolated in the
      Nottingham area of the United Kingdom.
AB  - DNA probes for specific integrase genes were used to study 122 R plasmids
      encoding the predominant trimethoprim-insusceptible type Ia dihydrofolate
      reductase (DHFR) found in clinical isolates of Escherichia coli. The predominance
      of the type Ia DHFR was thought to result from the location of its gene on
      transposon Tn7, but of trimethoprim R plasmids carrying this gene that were
      collected between 1978 and 1983, between 1987 and 1988, and during 1992, only
      49/60 (81.6%), 30/43 (69.8%) and 9/19 (47.4%) respectively hybridized with a
      probe for the Tn7 integrase gene. It has been suggested that novel genetic
      elements termed 'integrons' may play an important role in the dissemination of
      antibiotic resistance genes. Known integrons encode an integrase similar to that
      encoded by transposon Tn21, and 28 Tn7-negative plasmids (10/60 from 1978-83,
      10/43 from 1987-8 and 8/19 from 1992) showed homology with a probe specific for
      the Tn21 integrase gene. Six plasmids were negative with both probes. It is
      concluded that Tn7 has played an important role in the dissemination of the gene
      encoding the type Ia DHFR amongst clinical isolates of E. coli in the Nottingham
      region of the UK, but that other genetic structures, some of which seem to have
      an integrase function similar to that of known integrons, may be playing an
      increasingly significant role.

PMID- 8157571
TI  - Characterization of a beta-lactamase from Clostridium clostridioforme.
AB  - A beta-lactamase-producing strain of Clostridium clostridioforme isolated from
      human peritoneal fluid was examined by MIC testing and enzyme characterization.
      MICs of penicillins (64-512 mg/L) were higher than those of cephalosporins (8-128
      mg/L); the strain was susceptible to cefoxitin (8 mg/L) and imipenem (1 mg/L). No
      enhancement of cephalosporin activity occurred when clavulanate was also added,
      but a limited degree of enhancement of penicillin activity (resulting in beta
      lactam MICs higher than available NCCLS breakpoints) occurred when clavulanate,
      sulbactam or tazobactam was added simultaneously. By contrast, addition of BRL
      42715 with amoxycillin, ticarcillin or piperacillin led to a drop in beta-lactam
      MICs from 512 to < or = 1 mg/L, with a drop from 64 to 1 mg/L when BRL 42715 was
      added with cefotaxime. All inhibitors were added at fixed concentrations of 2
      mg/L. As determined spectrophotometrically, the enzyme hydrolysed penicillin G,
      cloxacillin and piperacillin (Vmax values (%) 372, 1816, 1001, respectively
      relative to cephaloridine) more efficiently than cephalosporins (69-191, with
      cephaloridine as 100%). Km values (microM) varied between 30-308 microM
      (penicillins) and 2-20 microM (cephalosporins). Relative enzyme efficiency
      (relative Vmax/Km with cephaloridine as 100) varied from 21-100 (cephalosporins)
      and 8-77 (penicillins). IC50 values (microM) with nitrocefin, piperacillin and
      penicillin G substrates (concentrations 20, 100 and 20 microM, respectively) were
      > 1000, 7, 3.5 (clavulanate); > 1000, 300, 59 (sulbactam), > 1000, 29, 7.7
      (tazobactam); 0.0004, 0.001, 0.0018 (BRL 42715). The enzyme was not inhibited by
      EDTA, cefoxitin, cloxacillin or aztreonam, but was inhibited by pCMB.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8157572
TI  - Prophylaxis after splenectomy.

PMID- 8157573
TI  - The effect of glycerol monolaurate on growth of, and production of toxic shock
      syndrome toxin-1 and lipase by, Staphylococcus aureus.
AB  - The effects of glycerol monolaurate on the growth of, and production of Toxic
      Shock Syndrome Toxin-1 (TSST-1) and lipase by, Staphylococcus aureus FRI 1187
      were investigated in batch and continuous culture models using a defined
      synthetic medium. The growth and yield of S. aureus depended on glycerol
      monolaurate concentration, pH of the environment and the inoculum size. The MICs
      for glycerol monolaurate of 29 S. aureus isolates, determined in a complex
      medium, were between 10 and 20 mg/L with a 10(3) to 10(4) cfu inoculum; a 1000
      fold increase in inoculum size increased the MIC five-fold. In continuous
      culture, glycerol monolaurate increased the cell yield of S. aureus. In batch
      cultures with 17 mg/L glycerol monolaurate, TSST-1 and lipase production by S.
      aureus was delayed and their specific production was not decreased compared with
      cultures without glycerol monolaurate. At 150 mg/L glycerol monolaurate, growth
      and toxin production were decreased. The lipase of S. aureus hydrolyzed glycerol
      monolaurate. The reduction of toxin production was associated with effects on S.
      aureus growth, and these effects might have been relieved after lipase had been
      produced.

PMID- 8157574
TI  - Effects of cefpirome in comparison with cefuroxime against human
      polymorphonuclear leucocytes in vitro.
AB  - The interaction of cefpirome and cefuroxime, with human polymorphonuclear
      leucocytes (PMNs) was examined. The effects of therapeutic concentration (1, 10,
      and 50 mg/L) of both antimicrobial agents on the adherence, spontaneous mobility,
      chemotaxis, chemokinesis, phagocytosis and candidacidal capacity were studied in
      vitro. No statistically significant variations, in relation to the control, were
      observed in the ability of PMNs to adhere to nylon fibre at the concentrations of
      cefuroxime and cefpirome used. With both antimicrobial agents, PMN mobility
      increased as the antibiotic concentration was increased. A statistically
      significant increase (P < 0.05) in spontaneous mobility, chemotaxis and
      chemokinesis was observed with cefpirome at only 10 mg/L. However, only
      spontaneous mobility was increased significantly with cefuroxime at 10 mg/L. The
      strongest effects were observed with cefpirome at 50 mg/L with variations of
      about 70% (P < 0.01), in chemotaxis and chemokinesis. In general, cefpirome had a
      positive effect on phagocytosis and candidacidal power, which was significant at
      a concentration of 50 mg/L (P < 0.01). Cefuroxime, in general, produced no
      modifications in either phagocytosis or candidacidal power.

PMID- 8157575
TI  - Effect of antimicrobial therapy on the gastrointestinal bacterial flora,
      infection and mortality in mice exposed to different doses of irradiation.
AB  - The effect of antimicrobial therapy on gut flora, sepsis, and mortality was
      investigated in C3H/HeN female mice irradiated with 7.0, 8.0 or 8.5 Gy or 60Co.
      The antimicrobial agents tested were metronidazole, penicillin, imipenem,
      gentamicin and ofloxacin. In control mice, the greatest reduction of lactose
      fermenting organisms (1.7-2.8 logs) occurred on day 8 after irradiation and were
      related directly to radiation doses. After day 8, lactose fermenting organism
      levels increased and the increases were associated with mortality due to
      Enterobacteriaceae sepsis. Irradiation reduced the populations of strict
      anaerobic bacteria in control mice by 2-8 logs, and these remained at low levels.
      Treatment with either metronidazole or penicillin resulted in greater reductions
      of strict anaerobic bacteria than occurred in the controls and induced earlier
      and greater increases in lactose fermenting organisms and associated mortality.
      Therapies with either gentamicin or ofloxacin resulted in lesser reductions of
      strict anaerobic bacteria (1.1-2.2 logs) than occurred in controls, and caused
      greater decreases in lactose fermenting organisms and mortality. The changes in
      the bacterial flora and mortality following imipenem treatment were similar to
      controls. These data demonstrate that in animals exposed to irradiation,
      antimicrobial agents effective against strict anaerobic bacteria can be
      deleterious, but antimicrobial agents effective against lactose fermenting
      organisms may be beneficial.

PMID- 8157576
TI  - Molecular aspects of methicillin resistance in Staphylococcus aureus.
AB  - All clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates examined
      so far contain the mecA gene, a 2130bp stretch of DNA of non-staphylococcal
      origin which, together with a larger block (up to 40-60 Kb) of 'foreign' DNA, is
      incorporated into the staphylococcal chromosome. mecA encodes for the 78 Kd
      penicillin-binding protein (PBP) 2A, which has very low affinity for beta-lactam
      antibiotics. The sequence of the mecA gene contains structural motifs
      characteristic of cell wall synthetic transpeptidases. It is generally assumed
      that the mecA gene product (PBP 2A) acts as a surrogate enzyme which takes over
      the task of cell wall synthesis from the normal complement of staphylococcal
      PBPs, since the latter are inhibited by relatively low (e.g. methicillin)
      concentrations of beta-lactam antibiotics. While direct biochemical evidence for
      a transpeptidase activity in PBP 2A is still missing, the essentiality of an
      intact mecA gene for the expression of high-level methicillin resistance has been
      clearly established by transposon inactivation experiments. On the other hand, it
      was already noted some time ago that an intact mecA and its gene product PBP 2A
      alone cannot be fully in control of the resistant phenotype, since all MRSA
      isolates, irrespective of their MIC values (from as low as 3 mg/L or as high as
      1600 mg/L), were found to contain comparable amounts of PBP 2A. Such major
      disparities between cellular amounts of PBP 2A and the antibiotic MIC values
      suggested that a factor or factors of unknown nature ('factor X') other than the
      mecA gene product also played an essential role in the phenotypic expression of
      resistance. The same conclusion was reached in early genetic studies in which
      methicillin resistance could be reduced by insertional inactivation of a
      chromosomal site (omega 2003) within the so-called femA gene--(factor essential
      for the expression of methicillin resistance) outside the mecA determinant. More
      recently, several additional chromosomal sites were identified outside the mecA
      gene in which transposon inactivation reduced the level of beta-lactam
      resistance. The importance of these genes becomes clear if one realizes that it
      is the appropriate functioning of these determinants (in the genetic background
      of MRSA) rather than the quantity of PBP 2A in the cells that seems to determine
      the MIC value of an MRSA isolate. It is not clear at the present time how many
      such 'auxiliary genes' exist and exactly how these gene co-operate with the mecA
      gene in bringing about high-level beta-lactam resistance.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8157577
TI  - Amphotericin B lipid complex in the treatment of experimental cryptococcal
      meningitis and disseminated candidosis.
AB  - In the quest for safer and more effective antifungal agents, amphotericin B (AMB)
      has been placed in a variety of lipid preparations. In this study, we examined
      the efficacy of amphotericin B lipid complex (ABLC) on experimental cryptococcal
      meningitis and disseminated candidosis. This formulation is relatively safe
      compared to the parent compound, and therefore doses ten times greater than the
      commercial amphotericin B deoxycholate can be given to rabbits. Although at equal
      doses the ABLC preparation is less potent than AMB, a higher dose of ABLC was
      rapidly fungicidal in the contexts of both a central nervous system infection
      with Cryptococcus neoformans during immune suppression, and a heart and kidney
      infection with Candida albicans. Rapid sterilization of tissue should be a goal
      of antifungal drug therapy, particularly in the immune compromised host. From
      these studies, this AMB lipid formulation has the ability to produce rapid
      fungicidal activity in vivo, but it requires higher doses than AMB deoxycholate.
      Clinical trials in humans must examine carefully the therapeutic-toxic ratio in
      dose-escalation protocols to determine the optimal dosage strategy for this
      agent.

PMID- 8157578
TI  - Efficiency of oxetanocin-G, a novel nucleoside against the woodchuck hepatitis
      virus.
AB  - Oxetanocin-G (OXT-G), a potent antiviral agent, is a novel nucleoside isolated
      from the culture filtrate of Bacillus megaterium. We investigated the antiviral
      effect of oral administration of OXT-G for five days on woodchuck hepatitis virus
      (WHV), in vivo, using 12 woodchucks. Woodchucks were randomized into each of four
      treatment groups according to the dose of OXT-G. Two out of six woodchucks
      treated with 1.0 or 2.0 mg/kg/day of OXT-G died. After treatment with OXT-G,
      serum levels of WHV-DNA significantly decreased in all woodchucks. However, the
      antiviral effect was only partial and levels of serum WHV-DNA returned after the
      cessation of treatment. The amount of viral replicative intermediates was
      decreased in livers of woodchucks treated with OXT-G. Although further study of
      the toxicity of this compound would be essential before studies in man can be
      carried out, OXT-G has potent antiviral activity against WHV and may deserve
      evaluation as an antiviral agent in the treatment of chronic hepatitis B
      infections in humans.

PMID- 8157579
TI  - Cefminox: correlation between in-vitro susceptibility and pharmacokinetics and
      serum bactericidal activity in healthy volunteers.
AB  - Plasma concentration of cefminox and serum bactericidal activity against four
      ATCC strains (Escherichia coli 25992, Klebsiella pneumoniae 13833, Serratia
      marcescens 8100 and Bacteroides fragilis 25285), were determined over a 24 h
      period after administration of cefminox 1 and 2 g to six healthy volunteers in a
      randomized, cross-over, single blind study. The increase observed in the area
      under the bactericidal curve (AUBC) with the 2 g dose was at least 3.5 times that
      seen with the 1 g dose for all four test strains and was larger than predicted by
      the corresponding increase (1.84 times) in the area under the serum concentration
      versus time curve (AUC); a correlation (r = 0.88, P = 0.0001) between the
      cefminox concentration and the serum bactericidal titres was, however, observed
      with all four strains tested. The MBC6h showed a better association with the
      serum bactericidal titre (P < 0.01) than did the MIC or MBC.

PMID- 8157580
TI  - The invisible image--a tutorial on photography with invisible radiation, Part 2:
      Fluorescence photography.

PMID- 8157581
TI  - Biofilms, the customized microniche.

PMID- 8157582
TI  - Mutations in NADH:ubiquinone oxidoreductase of Escherichia coli affect growth on
      mixed amino acids.
AB  - We isolated and characterized mutants defective in nuo, encoding NADH
      dehydrogenase I, the multisubunit complex homologous to eucaryotic mitochondrial
      complex I. By Southern hybridization and/or sequence analysis, we characterized
      three distinct mutations: a polar insertion designated nuoG::Tn10-1, a nonpolar
      insertion designated nuoF::Km-1, and a large deletion designated
      delta(nuoFGHIJKL)-1. Cells carrying any of these three mutations exhibited
      identical phenotypes. Each mutant exhibited reduced NADH oxidase activity, grew
      poorly on minimal salts medium containing acetate as the sole carbon source, and
      failed to produce the inner, L-aspartate chemotactic band on tryptone swarm
      plates. During exponential growth in tryptone broth, nuo mutants grew as rapidly
      as wild-type cells and excreted similar amounts of acetate into the medium. As
      they began the transition to stationary phase, in contrast to wild-type cells,
      the mutant cells abruptly slowed their growth and continued to excrete acetate.
      The growth defect was entirely suppressed by L-serine or D-pyruvate, partially
      suppressed by alpha-ketoglutarate or acetate, and not suppressed by L-aspartate
      or L-glutamate. We extended these studies, analyzing the sequential consumption
      of amino acids by both wild-type and nuo mutant cells growing in tryptone broth.
      During the lag and exponential phases, both wild-type and mutant cells consumed,
      in order, L-serine and L-aspartate. As they began the transition to stationary
      phase, both cell types consumed L-tryptophan. Whereas wild-type cells then
      consumed L-glutamate, glycine, L-threonine, and L-alanine, mutant cells utilized
      these amino acids poorly. We propose that cells defective for NADH dehydrogenase
      I exhibit all these phenotypes, because large NADH/NAD+ ratios inhibit certain
      tricarboxylic acid cycle enzymes, e.g., citrate synthase and malate
      dehydrogenase.

PMID- 8157583
TI  - Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins.
AB  - A fundamental ultrastructural feature shared by the spirochetal pathogens
      Treponema pallidum subsp. pallidum (T. pallidum) and Borrelia burgdorferi, the
      etiological agents of venereal syphilis and Lyme disease, respectively, is that
      their most abundant membrane proteins contain covalently attached fatty acids. In
      this study, we identified the fatty acids covalently bound to lipoproteins of B.
      burgdorferi and T. pallidum and examined potential acyl donors to these
      molecules. Palmitate was the predominant fatty acid of both B. burgdorferi and T.
      pallidum lipoproteins. T. pallidum lipoproteins also contained substantial
      amounts of stearate, a fatty acid not typically prevalent in prokaryotic
      lipoproteins. In both spirochetes, the fatty acids of cellular lipids differed
      from those of their respective lipoproteins. To characterize phospholipids in
      these organisms, spirochetes were metabolically labeled with [3H]palmitate or
      [3H]oleate; B. burgdorferi contained only phosphatidylglycerol and
      phosphatidylcholine, while T. pallidum contained phosphatidylglycerol,
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine,
      phosphatidylinositol, and cardiolipin. Although palmitate predominated in the
      lipoproteins, there were no apparent differences in the incorporation of these
      two fatty acids into phospholipids (putative acyl donors). Phospholipase A1 and
      A2 digestion of phosphatidylcholine from B. burgdorferi and T. pallidum labeled
      with either [3H]palmitate or [3H]oleate also revealed that neither fatty acid was
      incorporated preferentially into the 1 and 2 positions (potential acyl donor
      sites) of the glycerol backbone. The combined findings suggest that fatty acid
      utilization during lipoprotein synthesis is determined largely by the fatty acid
      specificities of the lipoprotein acyl transferases. These findings also provide
      the basis for ongoing efforts to elucidate the relationship between lipoprotein
      acylation and the physiological functions and inflammatory activities of these
      molecules.

PMID- 8157584
TI  - Metabolism of naphthalene, fluorene, and phenanthrene: preliminary
      characterization of a cloned gene cluster from Pseudomonas putida NCIB 9816.
AB  - A modified cloning procedure was used to obtain large DNA insertions (20 to 30
      kb) from Pseudomonas putida NCIB 9816 that expressed polycyclic aromatic
      hydrocarbon (PAH) transformation activity in Escherichia coli HB101. Four
      subclones (16 [in both orientations], 12, and 8.5 kb in size) were constructed
      from the initial clones. Naphthalene, fluorene, and phenanthrene transformations
      were investigated in these eight NCIB 9816 clones by a simple agar plate assay
      method, which was developed to detect and identify potential PAH metabolites.
      Results indicated that the necessary genes encoding the initial ring fission of
      the three PAHs in E. coli cells are located in an 8.5-kb EcoRI-XhoI portion, but
      the lower-pathway genes are not present in a 38-kb neighborhood region. These
      NCIB 9816 clones could transform naphthalene and phenanthrene to salicylic acid
      and 1-hydroxy-2-naphthoic acid, respectively. With the same clones, fluorene was
      degraded to 9-hydroxyfluorene, 9-fluorenone, and two unidentified compounds.
      Genetic similarity between the NAH7 upper-pathway genes and the cloned NCIB 9816
      genes was confirmed by Southern blot DNA-DNA hybridization. In spite of this
      genetic similarity, the abilities of the two clusters to transform multiple PAHs
      were different. Under our experimental conditions, only the metabolites from
      naphthalene transformation by the NAH7 clone (pE317) were detected, whereas the
      NCIB 9816 clones produced metabolites from all three PAHs.

PMID- 8157585
TI  - Identification and characterization of genes involved in excision of the
      Lactococcus lactis conjugative transposon Tn5276.
AB  - The 70-kb transposon Tn5276, originally detected in Lactococcus lactis NIZO R5
      and carrying the genes for nisin production and sucrose fermentation, can be
      conjugally transferred to other L. lactis strains. Sequence analysis and
      complementation studies showed that the right end of Tn5276 contains two genes,
      designated xis and int, which are involved in excision. The 379-amino-acid int
      gene product shows high (up to 50%) similarity with various integrases, including
      that of the Tn916-related conjugative transposons. The xis gene product, like
      almost all known excisionase (Xis) proteins, is a small (68-residue), basic
      protein. Expression of both the Tn5276 int and xis genes is required for
      efficient excision of the ends of Tn5276 in Escherichia coli that appeared to be
      circularized in the excision process. Mutational analysis of the xis and int
      genes showed that excision efficiency is dependent on the integrity of the int
      gene but that an intact xis gene is also required for efficient excision.

PMID- 8157586
TI  - Pyruvate metabolism in Halobacterium salinarium studied by intracellular 13C
      nuclear magnetic resonance spectroscopy.
AB  - 13C nuclear magnetic resonance spectroscopy was used to study the metabolism of
      [2-13C]pyruvate in intact cells of Halobacterium salinarium. The spectra of these
      cells show that pyruvate is reduced to lactic acid and transaminated to alanine.
      The intensity of C-2 lactate is higher under anaerobic conditions than under
      aerobic conditions. When cells are grown in the absence of glucose, the level of
      C-2 lactate intensity is lower. In extracts of these cells, the level of NADH
      dependent lactate dehydrogenase activity is lower than that of cells grown in the
      presence of glucose. A C-5 glutamate resonance suggests the entry of pyruvate
      into the tricarboxylic acid cycle through acetyl-coenzyme A. In addition, the
      label is also observed at C-3 and C-4 of glutamate, signifying a pyruvate
      carboxylase-type reaction and scrambling of label at the fumarate-succinate stage
      plus malic enzyme operation, respectively. Citrate synthase and malic enzyme
      activity appear to be controlled by the growth conditions of H. salinarium.

PMID- 8157587
TI  - Cloning, sequencing, and disruption of a levanase gene of Bacillus polymyxa CF43.
AB  - The Bacillus polymyxa CF43 lelA gene, expressing both sucrose and fructan
      hydrolase activities, was isolated from a genomic library of B. polymyxa screened
      in Bacillus subtilis. The gene was detected as expressing sucrose hydrolase
      activity; B. subtilis transformants did not secrete the lelA gene product (LelA)
      into the extracellular medium. A 1.7-kb DNA fragment sufficient for lelA
      expression in Escherichia coli was sequenced. It contains a 548-codon open
      reading frame. The deduced amino acid sequence shows 54% identity with mature B.
      subtilis levanase and is similar to other fructanases and sucrases (beta-D
      fructosyltransferases). Multiple-sequence alignment of 14 of these proteins
      revealed several previously unreported features. LelA appears to be a 512-amino
      acid polypeptide containing no canonical signal peptide. The hydrolytic
      activities of LelA on sucrose, levan, and inulin were compared with those of B.
      subtilis levanase and sucrase, confirming that LelA is indeed a fructanase. The
      lelA gene in the chromosome of B. polymyxa was disrupted with a chloramphenicol
      resistance gene (cat) by "inter-gramic" conjugation: the lelA::cat insertion on a
      mobilizable plasmid was transferred from an E. coli transformant to B. polymyxa
      CF43, and B. polymyxa transconjugants containing the lelA::cat construct
      replacing the wild-type lelA gene in their chromosomes were selected directly.
      The growth of the mutant strain on levan, inulin, and sucrose was not affected.

PMID- 8157588
TI  - Cloning and nucleotide sequence of the glpD gene encoding sn-glycerol-3-phosphate
      dehydrogenase of Pseudomonas aeruginosa.
AB  - Nitrosoguanidine-induced Pseudomonas aeruginosa mutants which were unable to
      utilize glycerol as a carbon source were isolated. By utilizing PAO104, a mutant
      defective in glycerol transport and sn-glycerol-3-phosphate dehydrogenase (glpD),
      the glpD gene was cloned by a phage mini-D3112-based in vivo cloning method. The
      cloned gene was able to complement an Escherichia coli glpD mutant. Restriction
      analysis and recloning of DNA fragments located the glpD gene to a 1.6-kb EcoRI
      SphI DNA fragment. In E. coli, a single 56,000-Da protein was expressed from the
      cloned DNA fragments. An in-frame glpD'-'lacZ translational fusion was isolated
      and used to determine the reading frame of glpD by sequencing across the fusion
      junction. The nucleotide sequence of a 1,792-bp fragment containing the glpD
      region was determined. The glpD gene encodes a protein containing 510 amino acids
      and with a predicted molecular weight of 56,150. Compared with the aerobic sn
      glycerol-3-phosphate dehydrogenase from E. coli, P. aeruginosa GlpD is 56%
      identical and 69% similar. A similar comparison with GlpD from Bacillus subtilis
      reveals 21% identity and 40% similarity. A flavin-binding domain near the amino
      terminus which shared the consensus sequence reported for other bacterial
      flavoproteins was identified.

PMID- 8157589
TI  - De novo synthesis of thymidylate via deoxycytidine in dcd (dCTP deaminase)
      mutants of Escherichia coli.
AB  - dcd (dCTP deaminase) mutants of Escherichia coli were reported not to require
      thymidine for growth even though most of the thymidylate that is synthesized de
      novo arises from cytosine nucleotides through a pathway involving dCTP deaminase.
      We found, however, that the fresh introduction of dcd mutations into many strains
      of E. coli produced a requirement for thymidine for optimum aerobic growth, but
      the mutants readily reverted to prototrophy via mutations in other genes. One
      such mutation was in deoA, the gene for deoxyuridine phosphorylase. However, a
      dcd deo mutant became thymidine dependent once again if a cdd mutation (affecting
      deoxycytidine deaminase) were introduced. The results indicate that dcd mutants
      utilize an alternative pathway of TMP synthesis in which deoxycytidine and
      deoxyuridine are intermediates. A cdd mutation blocks the pathway by preventing
      the conversion of deoxycytidine to deoxyuridine, whereas a deoA mutation enhances
      it by sparing deoxyuridine from catabolism. The deoxycytidine must arise from
      dCTP or dCDP via unknown steps. It is not known to what extent this pathway is
      utilized in wild-type cells, which, unlike the dcd mutants, do not accumulate
      dCTP.

PMID- 8157590
TI  - Cloning and characterization of the socA locus which restores development to
      Myxococcus xanthus C-signaling mutants.
AB  - The csgA gene produces an intercellular signal during fruiting body formation of
      the myxobacterium Myxococcus xanthus. Sporulating pseudorevertants were isolated
      to allow us to understand the mechanism by which CsgA is perceived by cells and
      used to regulate developmental gene expression. Two strains, LS559 and LS560,
      which have closely linked transposon insertions, soc-559 (formerly csp-559) and
      soc-560 (formerly csp-560), respectively, regained all the developmental
      behaviors lost by the csgA mutation including the ability to ripple, form
      fruiting bodies, and sporulate. The sequence analysis of the socA locus revealed
      that there are three putative protein-coding regions, designated socA1, socA2,
      and socA3. The deduced amino acid sequence of socA1 exhibits characteristics of
      the short-chain alcohol dehydrogenase family. The deduced amino acid sequence of
      socA2 shares 48% identity with the frdD gene product of the frd operon in Proteus
      vulgaris which anchors fumarate reductase to the membrane. The deduced amino acid
      sequence of socA3 does not show homology to any known proteins. Genotypic
      complementation, Northern (RNA) blotting, DNA sequence analysis, and the pattern
      of gene expression all suggest that these three genes are polycistronic. Since
      the socA mutations effectively bypass CsgA, the question of why csgA is
      maintained in M. xanthus was examined by studying the long-term stability of socA
      spores. Unlike the wild type, socA mutant spores germinated on starvation agar.
      Transmission electron micrographs of spore thin sections revealed that
      germination is not due to an obvious structural deficiency of the socA spores.
      These results suggest that the ability of socA myxospores to survive long periods
      under unfavorable environmental conditions is severely comprised. Therefore, soxA
      appears to be essential for the development of M. xanthus.

PMID- 8157591
TI  - The sphR product, a two-component system response regulator protein, regulates
      phosphate assimilation in Synechococcus sp. strain PCC 7942 by binding to two
      sites upstream from the phoA promoter.
AB  - In the photosynthetic cyanobacterium Synechococcus sp. strain PCC 7942, the sphS
      and sphR genes were previously suggested to encode a typical pair of two
      component signal transduction proteins. A deletion mutant strain lacking these
      genes failed to exhibit induction of alkaline phosphatase, the phoA gene product,
      in response to phosphate limitation in the medium. The SphR protein was
      overexpressed in Escherichia coli and then purified to near homogeneity. A
      truncated form of the SphS polypeptide (named SphS*) was also isolated. Here, we
      demonstrate that purified SphR is phosphorylated by phosphotransfer from SphS and
      binds to two distinct sites upstream from the phoA promoter. From these results,
      we conclude that the SphS and SphR proteins are directly involved in the
      regulation of phoA transcription in response to phosphate limitation in
      Synechococcus species.

PMID- 8157592
TI  - Expansion of bacteriocin activity and host range upon complementation of two
      peptides encoded within the lactacin F operon.
AB  - Lactacin F is a membrane-active bacteriocin produced by Lactobacillus johnsonii
      VPI11088 (Laf+). The genetic determinants encoding lactacin F are organized in a
      1-kb polycistronic operon composed of a promoter (P(laf)), three genes (lafA,
      lafX, and ORFZ), and a functional rho-independent transcription terminator. Two
      Laf- derivatives of VPI11088, designated NCK64 and NCK65, were characterized.
      NCK64 contained a frameshift mutation in the lafA gene causing premature
      termination of translation. NCK65 harbored a 10-kb chromosomal deletion covering
      the laf operon. When the lafA gene was cloned independently and expressed in
      NCK65, bacteriocin activity was limited to L. helveticus 87, only one of the six
      known lactacin F-sensitive (Lafs) indicators. When lafX was introduced into
      NCK65, no bacteriocin activity against any of the sensitive strains was detected.
      Genetic combination of lafA and lafX, in cis or in trans, restored bacteriocin
      activity against all Lafs indicators. When two NCK65 clones containing either
      lafA or lafX were plated slightly apart on agar plates, fully active lactacin F
      was present in the intervening area where the two excreted gene products, LafA
      and LafX, diffused together. The genetic analysis revealed that the interaction
      of two bacteriocinogenic peptides encoded within the laf operon is likely to
      participate in the formation of poration complexes in the membranes of
      susceptible bacteria.

PMID- 8157593
TI  - The internal pH of the forespore compartment of Bacillus megaterium decreases by
      about 1 pH unit during sporulation.
AB  - Previous work has shown that the internal pH of dormant spores of Bacillus
      species is more than 1 pH U below that of growing cells but rises to that of
      growing cells in the first minutes of spore germination. In the present work the
      internal pH of the whole Bacillus megaterium sporangium was measured by the
      distribution of the weak base methylamine and was found to decrease by
      approximately 0.4 during sporulation. By using fluorescence ratio image analysis
      with a fluorescein derivative, 2',7'-bis(2-carboxyethyl)-5 (and -6)
      carboxyfluorescein (BCECF), whose fluorescence is pH sensitive, the internal pH
      of the mother cell was found to remain constant during sporulation at a value of
      8.1, similar to that in the vegetative cell. Whereas the internal pH of the
      forespore was initially approximately 8.1, this value fell to approximately 7.0
      approximately 90 min before synthesis of dipicolinic acid and well before
      accumulation of the depot of 3-phosphoglyceric acid. The pH in the forespore
      compartment was brought to that of the mother cell by suspending sporulating
      cells in a pH 8 potassium phosphate buffer plus the ionophore nigericin to clamp
      the internal pH of the cells to that of the external medium. We suggest that at a
      minimum, acidification of the forespore may regulate the activity of
      phosphoglycerate mutase, which is the enzyme known to be regulated to allow 3
      phosphoglyceric acid accumulation during sporulation.

PMID- 8157594
TI  - Assembly of LamB and OmpF in deep rough lipopolysaccharide mutants of Escherichia
      coli K-12.
AB  - Assembly of the OmpF and LamB proteins was kinetically retarded in deep rough
      lipopolysaccharide mutants of Escherichia coli K-12. OmpF assembly was affected
      at the step of conversion of metastable trimers to stable trimers, whereas LamB
      assembly was influenced both at the monomer-to-metastable trimer and metastable
      to-stable trimer steps. These assembly defects were reversed in the presence of
      the sfaA1 and sfaB3 suppressor alleles, which were isolated by using ompF
      assembly mutants.

PMID- 8157595
TI  - FlgD is a scaffolding protein needed for flagellar hook assembly in Salmonella
      typhimurium.
AB  - FlgD is known to be absolutely required for hook assembly, yet it has not been
      detected in the mature flagellum. We have overproduced and purified FlgD and
      raised an antibody against it. By using this antibody, we have detected FlgD in
      substantial amounts in isolated basal bodies from flgA, flgE, flgH, flgI, flgK,
      and fliK mutants, in much smaller amounts in those from the wild type and flgL,
      fliA, fliC, fliD, and fliE mutants, and not at all in those from flgB, flgD,
      flgG, and flgJ mutants. In terms of the morphological assembly pathway, these
      results indicate that FlgD is first added to the structure when the rod is
      completed and is discarded when the hook, having reached its mature length, has
      the first of the hook-filament junction proteins, FlgK, added to its tip.
      Immunoelectron microscopy established that FlgD initially is located at the
      distal end of the rod and eventually is located at the distal end of the hook.
      Thus, it appears to act as a hook-capping protein to enable assembly of hook
      protein subunits, much as another flagellar protein, FliD, does for the flagellin
      subunits of the filament. However, whereas FliD is associated with the filament
      tip indefinitely, FlgD is only transiently associated with the hook tip; i.e., it
      acts as a scaffolding protein. When FlgD was added to the culture medium of a
      flgD mutant, cells gained motility; thus, although the hook cap is normally added
      endogenously, it can be added exogenously. When culture media were analyzed for
      the presence of hook protein, it was found only with the flgD mutant and, in
      smaller amounts, the fliK (polyhook) mutant. Thus, although FlgD is needed for
      assembly of hook protein, it is not needed for its export.

PMID- 8157596
TI  - Analysis of a Het- mutation in Anabaena sp. strain PCC 7120 implicates a
      secondary metabolite in the regulation of heterocyst spacing.
AB  - Transposon-generated mutant N10 of Anabaena sp. strain PCC 7120 has a Het-
      phenotype (A. Ernst, T. Black, Y. Cai, J.-M. Panoff, D. N. Tiwari, and C. P.
      Wolk, J. Bacteriol. 174:6025-6032, 1992). Reconstruction of the transposon
      mutation reproduced a Het- phenotype, but reconstructions with other insertions
      at the position of the transposon produced strains that form multiple contiguous
      heterocysts. Sequence analysis around the site of insertion of the transposon
      showed that the insertion lies within the 5' end of an 861-bp open reading frame
      (ORF) (hetN). The product of translation of hetN (HetN) shows extensive
      similarity to NAD(P)H-dependent oxidoreductases that are involved in biosyntheses
      of fatty acids, poly-beta-hydroxybutyrate, nod factor, and polyketides. A second,
      1,518-bp ORF (hetM) that ends 556 bp 5' from the start of hetN appears to encode
      a protein that has at least two functional domains: its amino terminus is similar
      to an acyl carrier protein, while its central portion is similar to domains of
      proteins that perform reductive reactions. A third, 711-bp ORF (hetI) encoded on
      the opposite strand ends 42 bp away from the 3' end of hetN. The protein encoded
      by hetI, HetI, is similar to Sfp from Bacillus subtilis and EntD from Escherichia
      coli, proteins that are required for the biosynthesis or export of cyclic
      peptides. Clones from a lambda-EMBL3 library that contain the wild-type DNA for
      hetN do not complement the hetN::Tn5-1063 mutation in N10. The presence of hetN,
      as the only ORF, on a replicating plasmid suppresses heterocyst formation in wild
      type cells, whereas the additional presence of hetI alleviates this effect.

PMID- 8157597
TI  - Intracellular generation of superoxide as a by-product of Vibrio harveyi
      luciferase expressed in Escherichia coli.
AB  - Luciferase genes are widely used as reporters of gene expression because of the
      high sensitivity of chemiluminescence detection and the possibility of monitoring
      light production in intact cells. We engineered fusions of the Escherichia coli
      soxS promoter to the luciferase structural genes (luxAB) from Vibrio harveyi.
      Since soxS transcription is positively triggered by the activated SoxR protein in
      response to agents such as paraquat that generate intracellular superoxide, we
      hoped to use this construct as a sensitive reporter of redox stress agents.
      Although a soxR+ soxS'::luxAB fusion exhibited a paraquat-inducible synthesis of
      luciferase, a smaller increase was consistently observed even in the absence of
      known soxRS inducers. This endogenous induction was soxR dependent and was
      further characterized by introducing a plasmid carrying the luciferase structural
      genes without the soxS promoter into a strain carrying a soxS'::lacZ fusion in
      the bacterial chromosome. These cells exhibited increased beta-galactosidase
      expression as they grew into mid-log phase. This increase was ascribed to
      luciferase activity because beta-galactosidase induction was suppressed (but not
      eliminated) when the substrate n-decanal was present in the medium. The
      soxS'::luxAB plasmid transformed superoxide dismutase-deficient strains very
      poorly under aerobic conditions but just as efficiently as a control plasmid
      under anaerobic conditions. The production of hydrogen peroxide, the dismutation
      product of superoxide anion, was significantly increased in strains carrying
      bacterial luciferase and maximal in the absence of n-decanal. Taken collectively,
      these data point to the generation of significant amounts of intracellular
      superoxide by bacterial luciferase, the possible mechanism of which is discussed.
      In addition to providing insights into the role of superoxide in the activation
      of the SoxR protein, these results suggest caution in the interpretation of
      experiments using luciferase as a reporter of gene expression.

PMID- 8157598
TI  - Induction of Escherichia coli hydroperoxidase I by acetate and other weak acids.
AB  - Escherichia coli produces two independently regulated hydroperoxidases
      (catalases) that protect the cell from toxic concentrations of hydrogen peroxide.
      Hydroperoxidase I (HPI) is induced by hydrogen peroxide in an OxyR-dependent
      manner, while hydroperoxidase II (HPII) synthesis is regulated by an alternative
      sigma factor called RpoS (KatF). The activities of both hydroperoxidases increase
      as exponentially growing cells enter stationary phase. In this study, we examined
      the growth phase-dependent expression of HPI. Treatment of early-exponential
      phase cells with spent culture supernatant resulted in induction of HPI
      synthesis. Extracellular levels of hydrogen peroxide, accumulating in the culture
      supernatant during late exponential phase, were found to be lower than the
      concentrations normally required to induce OxyR-dependent synthesis of HPI. This
      finding suggested that factors other than hydrogen peroxide may play a role in
      HPI expression. Weak acids such as acetate, which accumulate in culture
      supernatant and have been implicated in the regulation of HPII, caused a sixfold
      increase in HPI expression. Increases in HPI synthesis, mediated by weak acids
      and spent culture fluid supernatant, could be prevented by chloramphenicol,
      indicating that de novo protein synthesis is required for induction. Expression
      studies using a plasmid-borne lacZ transcriptional fusion to katG, the structural
      gene for HPI, indicated that growth phase-dependent regulation of HPI occurs
      primarily at the level of transcription and is dependent on RpoS. These results
      suggest that there may be a common regulatory mechanism of HPI and HPII
      expression in addition to previously described independent control mechanisms.

PMID- 8157599
TI  - Characterization of the fliL gene in the flagellar regulon of Escherichia coli
      and Salmonella typhimurium.
AB  - filL is a small gene of unknown function that lies within the beginning of a
      large flagellar operon of Salmonella typhimurium and Escherichia coli. A
      spontaneous fliL mutant of S. typhimurium, containing a frameshift mutation about
      40% from the 3' end of the gene, was moderately motile but swarmed poorly,
      suggesting that FliL might be a component of the flagellar motor or switch.
      However, in-frame deletions of the E. coli gene, including an essentially total
      deletion, had little or no effect on motility or chemotaxis. Thus, FliL does not
      appear to have a major role in flagellar structure or function and is therefore
      unlikely to be a component of the motor or switch; the effect on motility caused
      by truncation of the gene is probably an indirect one.

PMID- 8157600
TI  - Isolation and characterization of yeast monomorphic mutants of Candida albicans.
AB  - A method was devised for the isolation of yeast monomorphic (LEV) mutants of
      Candida albicans. By this procedure, about 20 stable yeast-like mutants were
      isolated after mutagenesis with ethyl methane sulfonate. The growth rate of the
      mutants in different carbon sources, both fermentable and not, was
      indistinguishable from that of the parental strain, but they were unable to grow
      as mycelial forms after application of any of the common effective inducers,
      i.e., heat shock, pH alterations, proline addition, or use of GlcNAc as the
      carbon source. Studies performed with one selected strain demonstrated that it
      had severe alterations in the chemical composition of the cell wall, mainly in
      the levels of chitin and glucans, and in specific mannoproteins, some of them
      recognizable by specific polyclonal and monoclonal antibodies. It is suggested
      that these structural alterations hinder the construction of a normal hyphal
      wall.

PMID- 8157601
TI  - Role of the TonB amino terminus in energy transduction between membranes.
AB  - Escherichia coli TonB protein is an energy transducer, coupling cytoplasmic
      membrane energy to active transport of vitamin B12 and iron-siderophores across
      the outer membrane. TonB is anchored in the cytoplasmic membrane by its
      hydrophobic amino terminus, with the remainder occupying the periplasmic space.
      In this report we establish several functions for the hydrophobic amino terminus
      of TonB. A G-26-->D substitution in the amino terminus prevents export of TonB,
      suggesting that the amino terminus contains an export signal for proper
      localization of TonB within the cell envelope. Substitution of the first membrane
      spanning domain of the cytoplasmic membrane protein TetA for the TonB amino
      terminus eliminates TonB activity without altering TonB export, suggesting that
      the amino terminus contains sequence-specific information. Detectable TonB cross
      linking to ExbB is also prevented, suggesting that the two proteins interact
      primarily through their transmembrane domains. In vivo cleavage of the amino
      terminus of TonB carrying an engineered leader peptidase cleavage site eliminates
      (i) TonB activity, (ii) detectable interaction with a membrane fraction having a
      density intermediate to those of the cytoplasmic and outer membranes, and (iii)
      cross-linking to ExbB. In contrast, the amino terminus is not required for cross
      linking to other proteins with which TonB can form complexes, including FepA.
      Additionally, although the amino terminus clearly is a membrane anchor, it is not
      the only means by which TonB associates with the cytoplasmic membrane. TonB
      lacking its amino-terminal membrane anchor still remains largely associated with
      the cytoplasmic membrane.

PMID- 8157602
TI  - Chloroperoxidase from Streptomyces lividans: isolation and characterization of
      the enzyme and the corresponding gene.
AB  - For the first time, a halogenating enzyme which is not known to produce
      halogenated metabolites has been isolated from a bacterial strain. The gene
      encoding the nonheme chloroperoxidase (CPO-L) from Streptomyces lividans TK64 was
      cloned, and its gene product was characterized. S. lividans TK64 produced only
      very small amounts of the enzyme. After cloning of the gene into Streptomyces
      aureofaciens Tu24-88, the enzyme was overexpressed up to 3,000-fold. Based on the
      overexpression, a simple purification procedure using acid precipitation and
      hydrophobic interaction chromatography was developed. Thus, 54 mg of homogeneous
      CPO-L could be obtained from 27 g (wet weight) of mycelium. The native enzyme has
      a molecular weight of 64,000 and consists of two identical subunits. The enzyme
      does not exhibit an absorption peak in the Soret region of the optical spectrum.
      X-ray fluorescence spectroscopy revealed that the enzyme does not contain any
      metal ions in equimolar amounts. CPO-L showed cross-reaction with antibodies
      raised against the nonheme chloroperoxidase from Pseudomonas pyrrocinia but not
      with antibodies raised against CPO-T from S. aureofaciens Tu24. CPO-L exhibits
      substrate specificity only for chlorination, not for bromination. Therefore,
      monochlorodimedone is only brominated by CPO-L, whereas indole is brominated and
      chlorinated. The functional chloroperoxidase gene was located on a 1.9-kb SalI
      DNA fragment. DNA sequence analysis revealed an open reading frame encoding a
      predicted polypeptide of 276 amino acids. The overall identity of the amino acid
      sequence to that of chloroperoxidase from P. pyrrocinia was 71%, whereas that to
      bromoperoxidase BPO-A2 from S. aureofaciens ATCC 10762 was only 42%.

PMID- 8157603
TI  - Analysis of duplicated gene sequences associated with tfdR and tfdS in
      Alcaligenes eutrophus JMP134.
AB  - Plasmid pJP4 of Alcaligenes eutrophus JMP134 encodes the degradation of 2,4
      dichlorophenoxyacetic acid. A 1.2-kb BamHI-XhoI region of the restriction
      fragment BamHI-E has been proposed to contain the regulatory gene tfdR (A. R.
      Harker, R. H. Olsen, and R. J. Seidler, J. Bacteriol. 171:314-320, 1989; B.
      Kaphammer, J. J. Kukor, and R. H. Olsen, J. Bacteriol. 172:2280-2286, 1990). When
      sequenced and analyzed, the region is shown to contain two incomplete open
      reading frames (ORFs) positioned divergently. The complete DNA sequence for one
      of the two ORFs was obtained by sequencing the adjacent restriction fragment
      BamHI-F. The DNA sequence reveals 100% identify with the regulatory gene tfdS of
      pJP4. An XbaI-PstI fragment, containing the complete ORF, encodes a 32,000-Da
      protein which binds to the promoter regions upstream from tfdA and tfdDII. The
      deduced amino acid sequence of the complete ORF shows similarity with sequences
      of activator proteins TcbR, CatM, and CatR of the LysR family. The complete ORF
      represents the regulatory gene tfdR. The deduced amino acid sequence of the
      incomplete ORF, situated divergently from tfdR, indicates similarity to
      chloromuconate cycloisomerases produced by genes tfdD and tcbD of plasmids pJP4
      and pP51, respectively. This ORF is identified as part of a putative
      isofunctional gene, tfdDII.

PMID- 8157604
TI  - Inducibility of the TOL catabolic pathway in Pseudomonas putida (pWW0) growing on
      succinate in continuous culture: evidence of carbon catabolite repression
      control.
AB  - The TOL catabolic genes in Pseudomonas putida (pWW0) are clustered in the upper
      operon, encoding enzymes for the conversion of toluene and xylenes to benzoate
      and toluates, and the meta-cleavage operon, encoding enzymes for the conversion
      of the benzoate and toluates to tricarboxylic acid cycle intermediates. In this
      study, it was shown that cells growing in a chemostat under succinate growth
      limiting conditions express both the upper and meta-cleavage pathways in response
      to o-xylene, a nonmetabolizable effector of the XylR regulatory protein. The
      dilution rate maintained in the succinate-limited chemostat cultures influenced
      the synthesis levels of TOL pathway enzymes, their steady-state levels, and their
      turnover rates. Cells growing in the presence of nonlimiting concentrations of
      succinate in continuous culture did not express pathway enzymes in response to
      the addition of o-xylene, which was due to a blockage at the transcriptional
      level. Expression of the meta-cleavage pathway in response to 2,3
      dimethylbenzoate, a nonmetabolizable effector of the XylS regulatory protein, was
      93% lower in cultures exposed to succinate at nonlimiting concentrations than in
      the succinate-limited chemostats. The mRNA level of xylS during nonlimited growth
      on succinate was very low compared with that in succinate-limited cultures,
      suggesting that suppression of expression of the meta-cleavage pathway is
      regulated mainly by the level of the XylS regulator.

PMID- 8157605
TI  - Nucleotide sequence of the rhamnose biosynthetic operon of Shigella flexneri 2a
      and role of lipopolysaccharide in virulence.
AB  - N1308, a chromosomal Tn5 mutant of Shigella flexneri 2a, was described previously
      as a lipopolysaccharide (LPS) mutant with a short O side chain. N1308 formed
      foci, but not plaques, in LLC-MK2 cell monolayers and was negative in the Sereny
      test. In this study, the wild-type locus inactivated in N1308 was cloned and
      further defined by means of complementation analysis. A 4.3-kb BstEII-XhoI
      fragment of S. flexneri 2a YSH6200 DNA was sufficient to restore both normal LPS
      and virulence phenotype to the mutant. DNA sequencing of this region revealed
      four genes, rfbA, rfbB, rfbC, and rfbD, encoding the enzymes required for the
      biosynthesis of activated rhamnose. The four genes were expressed in Escherichia
      coli, and the expected protein products were visualized by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. N1308 was shown to have normal levels of
      surface IpaC and IpaD, while a Western blot (immunoblot) of whole-cell lysates or
      outer membrane fractions indicated an elevated level of appropriately localized
      VirG. An in vitro invasion assay revealed that N1308 had normal primary invasive
      capacity and was able to multiply and move normally within the initial infected
      cell. However, it exhibited a significant reduction in its ability to spread from
      cell to cell in the monolayer. A double immunofluorescence assay revealed
      differences between LLC-MK2 cells infected with the wild-type YSH6000 and those
      infected with N1308. The wild-type bacteria elicited the formation of the
      characteristic F-actin tails, whereas N1308 failed to do so. However, N1308 was
      capable of inducing deposition of F-actin, which accumulated in a peribacterial
      fashion with only slight, if any, unipolar accumulation of the cytoskeletal
      protein.

PMID- 8157606
TI  - A gene (ccmA) required for carboxysome formation in the cyanobacterium
      Synechocystis sp. strain PCC6803.
AB  - A high-CO2-requiring mutant, G7, of Synechocystis sp. strain PCC6803 capable of
      inorganic carbon transport but unable to utilize the intracellular inorganic
      carbon pool for photosynthesis was isolated. Transmission electron micrographs of
      the mutant indicated that the mutant does not have any carboxysomes. A clone
      (pHPG7) with a 7.5-kbp DNA insert that transforms the G7 mutant to the wild-type
      phenotype was isolated from a genomic library of wild-type Synechocystis sp.
      strain PCC6803. Complementation tests with subclones identified the mutation site
      in G7 within 208 bp. Sequencing of nucleotides in this region elucidated an open
      reading frame, designated ccmA, encoding a protein of 302 amino acids. Cloning
      and sequence analysis of the respective G7 gene revealed an A-to-G substitution
      that results in an Asp-to-Gly substitution in the deduced amino acid. The result
      indicated that the ccmA gene encodes a protein essential for the formation of
      carboxysomes. An open reading frame encoding a proline-rich protein of 271 amino
      acids was found downstream of the ccmA gene, but no ccm-like genes or rbc operon
      was found in this region.

PMID- 8157607
TI  - Molecular analysis of the rfaD gene, for heptose synthesis, and the rfaF gene,
      for heptose transfer, in lipopolysaccharide synthesis in Salmonella typhimurium.
AB  - We report the analysis of three open reading frames of Salmonella typhimurium LT2
      which we identified as rfaF, the structural gene for ADP-heptose:LPS
      heptosyltransferase II; rfaD, the structural gene for ADP-L-glycero-D-manno
      heptose-6-epimerase; and part of kbl, the structural gene for 2-amino-3
      ketobutyrate CoA ligase. A plasmid carrying rfaF complements an rfaF mutant of S.
      typhimurium; rfaD and kbl are homologous to and in the same location as the
      equivalent genes in Escherichia coli K-12. The RfaF (heptosyl transferase II)
      protein shares regions of amino acid homology with RfaC (heptosyltransferase I),
      RfaQ (postulated to be heptosyltransferase III), and KdtA (ketodeoxyoctonate
      transferase), suggesting that these regions function in heptose binding. E. coli
      contains a block of DNA of about 1,200 bp between kbl and rfaD which is missing
      from S. typhimurium. This DNA includes yibB, which is an open reading frame of
      unknown function, and two promoters upstream of rfaD (P3, a heat-shock promoter,
      and P2). Both S. typhimurium and E. coli rfaD genes share a normal consensus
      promoter (P1). We postulate that the yibB segment is an insertion into the line
      leading to E. coli from the common ancestor of the two genera, though it could be
      a deletion from the line leading to S. typhimurium. The G+C content of the
      rfaLKZYJI genes of both S. typhimurium LT2 and E. coli K-12 is about 35%, much
      lower than the average of enteric bacteria; if this low G+C content is due to
      lateral transfer from a source of low G+C content, it must have occurred prior to
      evolutionary divergence of the two genera.

PMID- 8157608
TI  - Molecular characterization of the Erwinia chrysanthemi kdgK gene involved in
      pectin degradation.
AB  - The pathways of pectin and galacturonate catabolism in Erwinia chrysanthemi
      converge to form a common intermediate, 2-keto-3-deoxygluconate (KDG), which is
      phosphorylated by KDG kinase encoded by the kdgK gene. We cloned the kdgK gene of
      E. chrysanthemi 3937 by complementing an Escherichia coli kdgK mutation, using an
      RP4-derivative plasmid. One of the kdgK R-prime plasmids harbored a DNA insert of
      about 80 kb and carried the uxuA and uxuB genes involved in glucuronate
      catabolism and the celY gene coding for an E. chrysanthemi cellulase. The kdgK
      and celY genes were precisely located on this plasmid, and their respective
      transcriptional directions were determined. The nucleotide sequence of the kdgK
      region indicated that the kdgK reading frame is 981 bases long, corresponding to
      a protein of 329 amino acids with a molecular mass of 36,377 Da. Analysis of the
      deduced primary amino acid sequence showed that this enzyme is a new member of
      the PfkB family of carbohydrate kinases. Expression of kdgK is controlled by a
      negative regulatory gene, kdgR, which represses all the steps of pectin
      degradation. Near the putative promoter of the kdgK gene, we identified a
      putative KdgR-binding site and demonstrated that the KdgR protein specifically
      binds in vitro to this DNA region. The KdgR-KDG couple directly mediates the
      phenomenon of repression or induction. The KDG kinase, by limiting the
      intracellular inducer concentration, appears to be a key enzyme in induction of
      the whole catabolic pathway.

PMID- 8157609
TI  - Characterization of the interaction of the glp repressor of Escherichia coli K-12
      with single and tandem glp operator variants.
AB  - The glp operons of Escherichia coli are negatively controlled by the glp
      repressor. Comparison of the repressor-binding affinities for consensus and
      altered consensus operators in vivo showed that all base substitutions at
      positions 3, 4, 5, and 8 from the center of the palindromic operator caused a
      striking decrease in repressor binding. Substitutions at other positions had a
      severe to no effect on repressor binding, depending on the base substitution. The
      results obtained indicate that the repressor binds with highest affinity to
      operators with the half-site WATKYTCGWW, where W is A or T, K is G or T, and Y is
      C or T. Strong cooperative binding of the repressor to tandem operators was
      demonstrated in vivo. Cooperativity was maximal when two 20-bp operators were
      directly repeated or when 2 bp separated the two operators. Cooperativity
      decreased with the deletion of 2 bp or the addition of 4 bp between the
      individual operators. Cooperativity was eliminated with a 6-bp insertion between
      the operators.

PMID- 8157610
TI  - Modification of peptidoglycan precursors is a common feature of the low-level
      vancomycin-resistant VANB-type Enterococcus D366 and of the naturally
      glycopeptide-resistant species Lactobacillus casei, Pediococcus pentosaceus,
      Leuconostoc mesenteroides, and Enterococcus gallinarum.
AB  - The biochemical basis for the acquired or natural resistance of various gram
      positive organisms to glycopeptides was studied by high-pressure liquid
      chromatographic analysis of their peptidoglycan UDP-MurNAc-peptide precursors. In
      all cases, resistance was correlated with partial or complete replacement of the
      C-terminal D-Ala-D-Ala-containing UDP-MurNAc-pentapeptide by a new precursor with
      a modified C terminus. Nuclear magnetic resonance analysis by sequential
      assignment showed that the new precursor encountered in Enterococcus faecium
      D366, a strain belonging to the VANB class, which expresses low-level resistance
      to vancomycin, was UDP-MurNAc-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-lactate, identical
      to that previously found in the VANA class, which expresses high-level resistance
      to vancomycin. High-pressure liquid chromatographic analyses, composition
      determinations, and digestion by R39 D,D-carboxypeptidase demonstrated the
      exclusive presence of the new precursor in Lactobacillus casei and Pediococcus
      pentosaceus, which are naturally highly resistant to glycopeptides. The low-level
      natural resistance of Enterococcus gallinarum to vancomycin was found to be
      associated with the synthesis of a new precursor identified as a UDP-MurNAc
      pentapeptide containing a C-terminal D-serine. The distinction between low and
      high levels of resistance to glycopeptides appeared also to depend on the
      presence or absence of a substantial residual pool of a D-Ala-D-Ala-containing
      UDP-MurNAc-pentapeptide.

PMID- 8157611
TI  - Cell cycle regulation of the Escherichia coli nrd operon: requirement for a cis
      acting upstream AT-rich sequence.
AB  - The expression of the nrd operon encoding ribonucleotide reductase in Escherichia
      coli has been shown to be cell cycle regulated. To identify the cis-acting
      elements required for the cell cycle regulation of the nrd promoter, different 5'
      deletions as well as site-directed mutations were translationally fused to a lacZ
      reporter gene. The expression of beta-galactosidase from these nrd-lacZ fusions
      in single-copy plasmids was determined with synchronously growing cultures
      obtained by repeated phosphate starvation as well as with exponentially growing
      cultures by flow cytometry analysis. Although Fis and DnaA, two regulatory
      proteins that bind at multiple sites on the E. coli chromosome, have been found
      to regulate the nrd promoter, the results in this study demonstrated that neither
      Fis nor DnaA was required for nrd cell cycle regulation. A cis-acting upstream AT
      rich sequence was found to be required for the cell cycle regulation. This
      sequence could be replaced by a different sequence that maintained the AT
      richness. A flow cytometry analysis that combined specific immunofluorescent
      staining of beta-galactosidase with a DNA-specific stain was developed and
      employed to study the nrd promoter activity in cells at specific cell cycle
      positions. The results of the flow cytometry analysis confirmed the results
      obtained from studies with synchronized cells.

PMID- 8157612
TI  - Characterization of the sigD transcription unit of Bacillus subtilis.
AB  - The sigma D factor of Bacillus subtilis is required for the transcription of the
      flagellin and motility genes as well as for wild-type chemotaxis. Southern blot
      and sequence analyses demonstrate that the structural gene for sigma D, sigD, is
      located immediately downstream of a region of DNA originally identified as the
      chemotaxis (che) locus and now renamed the fla/che region. In fact, sigD appears
      to be part of a very large operon (> 26 kb) containing genes which encode
      structural proteins that form the hook-basal body complex as well as regulatory
      proteins required for chemotaxis. Transposon insertions up to 24 kb upstream of
      sigD, within several of the genes for the hook-basal body components, give rise
      to only a moderate decrease in sigD expression. The transposon insertions,
      however, block sigma D activity as demonstrated by the lack of flagellin
      expression in strains bearing these insertions. These effects appear to arise
      from two types of regulation. In cis the transposon insertions appear to
      introduce a partial block to transcription of sigD from upstream promoter
      elements; in trans they disrupt genes whose gene products are required for sigma
      D activity. It appears that sigD transcription is initiated, at least in part, by
      a promoter many kilobases upstream of its translation start site and that
      transcription of the flagellin gene by sigma D is dependent on the formation of a
      functional hook-basal body complex. The possibility that sigD is part of the
      fla/che operon was further tested by the integration of an insertion plasmid,
      containing strong transcription terminators, 1.6 and 24 kb upstream of the sigD
      gene. In both cases, the introduction of the terminators resulted in a greater
      decrease of sigD expression than was caused by the plasmid sequences alone. These
      results indicate that wild-type transcription of sigD is dependent on promoter
      sequences > 24kb upstream of its structural gene and that the entire fla/che
      region forms a single operon.

PMID- 8157613
TI  - Regulation of sigma D expression and activity by spo0, abrB, and sin gene
      products in Bacillus subtilis.
AB  - Expression of sigma D protein and of the hag gene, which is transcribed by the
      sigma D holoenzyme, is not dependent on spo0, abrB, or sin gene products in
      Bacillus subtilis. Preliminary results, however, suggest that a signal mediated
      by the spo0K locus may be responsible for the inhibition of sigma D activity
      during the stationary phase.

PMID- 8157614
TI  - Cloning and characterization of a chromosomal gene cluster, pah, that encodes the
      upper pathway for phenanthrene and naphthalene utilization by Pseudomonas putida
      OUS82.
AB  - A 25-kb DNA SalI fragment cloned from the chromosomal DNA of Pseudomonas putida
      OUS82, which utilizes phenanthrene (Phn+) and naphthalene (Nah+), carried all of
      the genes necessary for upper naphthalene catabolism. Cosmid recombinant pIP7
      complemented both the Nah- and Phn- defects of OUS8211 (Trp-Nah-Phn
      Sal+[salicylate utilizing]Hna+[1-hydroxy-2-naphthoate utilizing]) and only the
      Phn- defect of OUS8212 (Trp-Nah-Phn-Sal-Hna+). The results indicate that strain
      OUS82 uses different pathways after o-hydroxycarboxylic aromatics in the
      catabolism of naphthalene and phenanthrene.

PMID- 8157615
TI  - Identification and characterization of genes encoding polycyclic aromatic
      hydrocarbon dioxygenase and polycyclic aromatic hydrocarbon dihydrodiol
      dehydrogenase in Pseudomonas putida OUS82.
AB  - Naphthalene and phenanthrene are transformed by enzymes encoded by the pah gene
      cluster of Pseudomonas putida OUS82. The pahA and pahB genes, which encode the
      first and second enzymes, dioxygenase and cis-dihydrodiol dehydrogenase,
      respectively, were identified and sequenced. The DNA sequences showed that pahA
      and pahB were clustered and that pahA consisted of four cistrons, pahAa, pahAb,
      pahAc, and pahAd, which encode ferredoxin reductase, ferredoxin, and two subunits
      of the iron-sulfur protein, respectively.

PMID- 8157616
TI  - Plasmids of the pT181 family show replication-specific initiator protein
      modification.
AB  - The rolling circle plasmids of Staphylococcus aureus regulate their replication
      by controlling initiator (Rep) protein synthesis. It was demonstrated recently
      that the pT181 initiator protein RepC is inactivated during pT181 replication by
      the addition of an oligodeoxynucleotide, giving rise to a new form, RepC* (A.
      Rasooly and R. P. Novick, Science, 262:1048-1050). We establish here that this
      initiator modification occurs with four other members of the pT181 family and
      that it occurs in Bacillus subtilis as well as S. aureus. These results suggest
      that Rep conversion to Rep* is probably universal among plasmids of the pT181
      family and is not host dependent.

PMID- 8157617
TI  - Analysis of the lipid moiety of lipopolysaccharide from Rhizobium tropici
      CIAT899: identification of 29-hydroxytriacontanoic acid.
AB  - The lipid moieties of two lipid A's isolated from the phenolic and aqueous
      fractions of lipopolysaccharide from Rhizobium tropici CIAT899 have been studied.
      Several 3-hydroxy fatty acids and two long-chain hydroxy fatty acids, 27
      hydroxyoctacosanoic acid, and 29-hydroxytriacontanoic acid were identified; the
      ratios of these acids are the same in both lipid A's. These results can be used
      for chemotaxonomic purposes.

PMID- 8157618
TI  - Molecular cloning, DNA sequence, and gene expression of the oxalyl-coenzyme A
      decarboxylase gene, oxc, from the bacterium Oxalobacter formigenes.
AB  - Oxalic acid, a highly toxic by-product of metabolism, is catabolized by a limited
      number of bacterial species by an activation-decarboxylation reaction which
      yields formate and CO2. oxc, the gene encoding the oxalic acid-degrading enzyme
      oxalyl-coenzyme A decarboxylase, was cloned from the bacterium Oxalobacter
      formigenes. The DNA sequence revealed a single open reading frame of 1,704 bp
      capable of encoding a 568-amino-acid protein with a molecular weight of 60,691.
      The identification of a presumed promoter region and a rho-independent
      termination sequence indicates that this gene is not part of a polycistronic
      operon. A PCR fragment encoding the open reading frame, when overexpressed in
      Escherichia coli, produced a product which cross-reacted antigenically with
      native enzyme on Western blots (immunoblots), appeared to form homodimers
      spontaneously, and exhibited enzymatic activity similar to that of the purified
      native enzyme.

PMID- 8157619
TI  - Nucleotide sequence of the aknA region of the aklavinone biosynthetic gene
      cluster of Streptomyces galilaeus.
AB  - A 3.4-kb BamHI fragment that is assumed to be a part of the aklavinone
      biosynthetic gene cluster of Streptomyces galilaeus 3AR-33 and contains the genes
      required for the early stage of polyketide biosynthesis was sequenced. The
      nucleotide sequence of the region that hybridizes to the actIII probe reveals the
      presence of a gene, aknA, whose deduced protein product is very similar to the
      ActIII protein and other known oxidoreductases. The predicted AknA protein is
      believed to be responsible for catalyzing the reduction of the keto group at the
      ninth carbon from the carboxyl terminus of the assembled polyketide to the
      corresponding secondary alcohol. The predicted AknA protein has a calculated
      molecular mass of 27,197 Da (261 amino acids) and the highly conserved sequence
      Gly-Xaa-Gly-Xaa-Xaa-Ala commonly seen in oxidoreductases. Cloning and sequence
      analysis of the aknA region of the 2-hydroxyaklavinone-producing strain S.
      galilaeus ANR-58 identified an alteration in the gene, confirming that the aknA
      gene is essential for aklavinone biosynthesis.

PMID- 8157620
TI  - Peptides containing a D-amino acid from frogs and molluscs.

PMID- 8157621
TI  - Rab3C is a synaptic vesicle protein that dissociates from synaptic vesicles after
      stimulation of exocytosis.
AB  - Rab3 proteins are small GTP-binding proteins of the Ras superfamily. Four highly
      homologous Rab3 proteins termed Rab3A, Rab3B, Rab3C, and Rab3D have been
      described. Rab3A has previously been shown to be a constituent of synaptic
      vesicles in neurons that undergoes membrane dissociation-association cycles
      during synaptic vesicle recycling. Here we report that Rab3C copurifies with
      Rab3A during the isolation of synaptic vesicles. Organelles immunoisolated with
      monoclonal antibodies directed against Rab3A led to a coenrichment of Rab3A and
      Rab3C, demonstrating that both Rab3 proteins are colocalized on the same
      organelle. In isolated nerve terminals, stimulation of neurotransmitter release
      resulted in a dissociation of Rab3C from synaptic vesicle and/or recycling
      membranes. This dissociation parallels that of Rab3A observed under the same
      conditions. In contrast, no change was observed in the membrane-association of
      Rab5, a Rab protein localized on early endosomes. We conclude that in the nervous
      system Rab3C is localized on synaptic vesicles and, like Rab3A, cycles on and off
      the synaptic vesicle membrane in parallel with exocytotic release of
      neurotransmitter.

PMID- 8157622
TI  - Dependence on NADH produced during glycolysis for beta-cell glucose signaling.
AB  - An increase in cytosolic ATP following glucose metabolism by pancreatic beta
      cells is the key signal initiating insulin secretion by causing blockade of ATP
      dependent K+ channels (KATP). This induces membrane depolarization, leading to an
      elevation in cytosolic Ca2+ ([Ca2+]i) and insulin secretion. In this report we
      identify the critical metabolic step by which glucose initiates changes in beta
      cell KATP channel activity, membrane potential, and [Ca2+]i. The signal stems
      from the glycolytic production of NADH during the oxidation of glyceraldehyde 3
      phosphate, which is subsequently processed into ATP by mitochondria via the
      operation of discrete shuttle systems.

PMID- 8157623
TI  - Chemical characterization of A beta 17-42 peptide, a component of diffuse amyloid
      deposits of Alzheimer disease.
AB  - A peptide corresponding to the amino acid sequence of A beta 17-42
      (LVFFAEDVGSNKGAIIGLMVGGVVIA) was isolated from Alzheimer Disease patient brains
      containing large deposits of diffuse-type amyloid. Brain homogenates were lysed
      in SDS and submitted to high speed centrifugations. A beta peptides were purified
      by size exclusion chromatography on Superose 12 and TSK 3000 SW columns. An A
      beta peptide with M(r) of 3,000 was recovered that on automatic gas-phase Edman
      degradation yielded the amino acid sequence of A beta starting at residue 17
      (Leu). The 3-kDa peptide was subsequently hydrolyzed with trypsin and reacted
      with CNBr, and the resulting peptides were separated by reverse phase high
      pressure liquid chromatography and characterized by amino acid analyses, peptide
      microsequencing, and mass spectrometry. Hydrolysis of beta-amyloid precursor
      protein 695 at Lys612-Leu613 or at Lys16-Leu17 of its A beta 1-42 derivative
      prevents the generation of neurotoxic A beta filaments, thus leading to the
      formation of A beta 17-42 localized in the diffuse amyloid deposits. An
      outstanding feature in the pathology of Alzheimer Disease is that the predominant
      A beta peptides have their C termini at position 42, whether in the cores of the
      neuritic plaques, in the vascular walls, or in the diffuse deposits. Based on
      these observations, we postulate that the accumulation of insoluble A beta N-42
      in Alzheimer Disease is due to the anomalous processing of the C-terminal region.

PMID- 8157624
TI  - Oncostatin M binds directly to gp130 and behaves as interleukin-6 antagonist on a
      cell line expressing gp130 but lacking functional oncostatin M receptors.
AB  - Oncostatin M (OM) and interleukin 6 (IL-6) are functionally related cytokines,
      which trigger similar biological responses because they share gp130 as a common
      signal transducing transmembrane receptor. While IL-6 recruits gp130 only upon
      binding to its specific receptor subunit (IL-6R alpha), reconstitution and cross
      linking experiments on cell membranes suggest that OM can directly interact with
      gp130 and that this interaction is necessary but not sufficient to stimulate
      cells. However, the issue of the direct binding between gp130 and OM, in the
      absence of any additional membrane component, remained essentially unclarified.
      In this paper we show that, uniquely among the family of cytokines that transduce
      through gp130, OM directly binds in vitro with a 10(-8) M affinity sgp130, a
      soluble form of gp130. Moreover, titration of sgp130 with OM inhibits the
      formation of a ternary complex comprising IL-6, sIL-6R alpha, and sgp130. These
      in vitro properties of OM are consistent with the additional finding that on
      human hepatoma Hep3B cells, which express gp130 but not functional OM receptors,
      OM does not mimic IL-6 activity, but rather behaves, at high doses, as an IL-6
      antagonist.

PMID- 8157625
TI  - A soluble exopolyphosphatase of Saccharomyces cerevisiae. Purification and
      characterization.
AB  - A soluble polyphosphatase of Saccharomyces cerevisiae, purified to apparent
      homogeneity, is monomeric with a molecular mass of 40 kDa. It acts as an
      exoenzyme in a processive mode releasing orthophosphate residues from long
      polyphosphate chains until pyrophosphate is reached. Polyphosphates of all the
      lengths examined are used as substrates with a preference for those of about 250
      residues. These are degraded with a kcat/Km near the limit for diffusion
      controlled reactions. At 37 degrees C, the enzyme releases about 500 phosphate
      residues/s. It does not act on pyrophosphate, ATP, or the cyclic form of
      tripolyphosphate. For optimal activity the enzyme requires magnesium, manganese,
      or cobalt.

PMID- 8157626
TI  - Mechanism of modulation of rat liver fructose-2,6-bisphosphatase by nucleoside
      triphosphates.
AB  - The mechanism of modulation of fructose-2,6-bisphosphatase of rat liver 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase by nucleoside triphosphates
      was studied by employing the Escherichia coli-expressed bisphosphatase domain and
      a COOH-terminal 30-amino acid truncated form. These forms had Km values for
      substrate and Ki values for products which were similar to those of the
      bisphosphatase of the intact bifunctional enzyme, but turnover numbers were 5
      fold higher. All forms also exhibited substrate inhibition that was relieved by
      GTP and ATP. The nucleoside triphosphates bound to the active site, since they
      were competitive inhibitors at subsaturating substrate concentrations. Guanosine
      was also a competitive inhibitor at subsaturating substrate concentrations but
      did not activate at saturating substrate. ATP and GTP had Kd values of 467 and
      110 microM, respectively, and 1 mol of nucleoside triphosphate/mol bound per mol
      of bisphosphatase. The Ki values for guanosine of two mutants, Lys356-->Ala and
      Arg360-->Ala, were unchanged from that of the wild-type enzyme. However, the Ki
      for GTP for Arg360-->Ala was 17-fold higher than that of the wild-type enzyme,
      whereas that for Lys356-->Ala was unchanged. It was concluded that 1) nucleoside
      triphosphate modulation of the bisphosphatase of the bifunctional enzyme involves
      a direct interaction with the active site of the bisphosphatase domain; and 2)
      the activation is caused by the phosphate moieties of GTP and ATP competing with
      the 2-phospho group of fructose-2,6-bisphosphate for the phosphoenzyme
      intermediate, thus relieving substrate inhibition.

PMID- 8157627
TI  - Regulation of phosphatidylinositol 4-kinase from the yeast Saccharomyces
      cerevisiae by CDP-diacylglycerol.
AB  - Regulation of the 45- and 55-kDa forms of Saccharomyces cerevisiae membrane
      associated phosphatidylinositol (PI) 4-kinase (ATP:phosphatidylinositol 4
      phosphotransferase) by phospholipids was examined using Triton X-100/phospholipid
      mixed micelles. CDP-diacylglycerol and phosphatidylglycerol inhibited 45-kDa PI 4
      kinase activity in a dose-dependent manner. Kinetic analyses of the 45-kDa PI 4
      kinase showed that phosphatidylglycerol was a competitive inhibitor with respect
      to PI (Ki = 2 mol %), and CDP-diacylglycerol was a mixed type of inhibitor with
      respect to PI (Ki = 4 mol %) and MgATP (Ki = 5 mol %). 55-kDa PI 4-kinase
      activity was not significantly affected by phospholipids. The physiological
      relevance of CDP-diacylglycerol inhibition of 45-kDa PI 4-kinase activity was
      examined using plasma membranes from inositol auxotrophic (ino1) cells.
      Immunoblot analysis showed that 45-kDa PI 4-kinase expression in plasma membranes
      was not affected by inositol starvation of ino1 cells. However, both 45-kDa PI 4
      kinase activity and its product PI 4-phosphate were reduced in plasma membranes
      from inositol-starved ino1 cells. The CDP-diacylglycerol concentration (9.6 mol
      %) in plasma membranes of inositol-starved ino1 cells was 12-fold higher than its
      concentration (0.8 mol %) in plasma membranes of inositol-supplemented cells.
      Plasma membranes of inositol-starved ino1 cells also had increased levels of
      phosphatidate, phosphatidylserine, phosphatidylethanolamine, and cardiolipin.
      However, these phospholipids did not affect pure 45-kDa PI 4-kinase activity. The
      concentration of CDP-diacylglycerol in plasma membranes of inositol-starved ino1
      cells was in the range of the inhibitor constants determined for CDP
      diacylglycerol by kinetic analyses using pure 45-kDa PI 4-kinase. These results
      raised the suggestion that 45-kDa PI 4-kinase activity may be regulated in vivo
      by CDP-diacylglycerol.

PMID- 8157628
TI  - Nonhomogeneous labeling of liver extra-mitochondrial acetyl-CoA. Implications for
      the probing of lipogenic acetyl-CoA via drug acetylation and for the production
      of acetate by the liver.
AB  - The labeling of liver extra-mitochondrial acetyl-CoA was investigated in isolated
      rat livers perfused with [2-(13)C]acetate, [1-(13)C]octanoate, or [1,2,3,4
      (13)C4]docosanoate and with drugs that undergo acetylation (phenylaminobutyrate,
      paraaminobenzoate, and sulfamethoxazole; singly or in combination). The 13C
      enrichment of mitochondrial acetyl-CoA was probed by the enrichment of R-beta
      hydroxybutyrate. The latter was not enriched from [1,2,3,4-(13)C4]docosanoate,
      thus excluding mitochondrial beta-oxidation of docosanoate. The 13C enrichment of
      extra-mitochondrial acetyl-CoA was probed by the enrichments of acetylated drugs
      and of free acetate. In most cases, the four probes yielded different
      enrichments. Thus, extra-mitochondrial acetyl-CoA appears nonhomogeneous.
      Competition between drugs alters the labeling of individual acetyl-CoA sub-pools.
      The labeling pattern of acetylated drugs suggests the existence of more than the
      two N-acetyltransferases identified so far by others. Our data question the
      possibility of probing the pool of lipogenic acetyl-CoA via drug acetylation.

PMID- 8157629
TI  - Sequencing and characterization of the ntp gene cluster for vacuolar-type Na(+)
      translocating ATPase of Enterococcus hirae.
AB  - We have previously reported the DNA and amino acid sequences for the three genes
      (ntpA, ntpB, and ntpK) encoding the A, B, and K (proteolipid) subunits,
      respectively, of Na(+)-translocating ATPase of a eubacterium Enterococcus hirae
      (Kakinuma, Y., Kakinuma, S., Takase, K., Konishi, K., Igarashi, K., and Yamato,
      I. (1993) Biochem. Biophys. Res. Commun. 195, 1063-1069). In this paper we report
      the entire nucleotide sequence of the ntp gene cluster coding for this
      multisubunit enzyme. The cluster contained eight other genes; the order of these
      11 genes was ntpF, -I, -K, -E, -C, -G, -A, -B, -D, -H, and -J, encoding proteins
      with predicted molecular weights of 14,255, 75,619, 16,036, 22,699, 38,162,
      11,409, 65,766, 51,139, 27,093, 7,164, and 48,869, respectively. The deduced
      amino acid sequences of these products suggested that NtpI and NtpJ are
      hydrophobic proteins and others are hydrophilic. The ntpI gene product, which
      possesses six membrane-spanning segments in its carboxyl-terminal half, resembled
      the 116-kDa subunit of vacuolar (V)-ATPase in clathrin-coated vesicles. In
      addition, the NtpE, NtpC, NtpG, and NtpD proteins resembled bovine kidney ATPase
      E subunit, Saccharomyces cerevisiae Vma6p, Manduca sexta V-ATPase 14-kDa subunit,
      and Sulfolobus acidocaldarius gamma subunit, respectively, although the
      similarities between their amino acid sequences were moderate. Other gene
      products (NtpF and NtpH) did not show significant sequence similarity to other V
      ATPase subunits. Since NtpA, NtpB, and NtpK are homologous counterparts of V
      ATPase, these findings suggest that the molecular architecture of E. hirae Na(+)
      ATPase complex corresponds to the V-type H(+)-ATPase complex distributed in
      various eukaryotic endomembrane systems. The sequence of the NtpJ product was
      similar to those of K+ transport systems of S. cerevisiae (Trk1 and Trk2); its
      meaning will be discussed. This is the first demonstration of a eukaryotic V
      ATPase-like Na+ pump in bacteria.

PMID- 8157630
TI  - Isothermal titration calorimetric studies of Saccharomyces cerevisiae myristoyl
      CoA:protein N-myristoyltransferase. Determinants of binding energy and catalytic
      discrimination among acyl-CoA and peptide ligands.
AB  - Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) is
      an essential, monomeric enzyme that catalyzes the transfer of myristate from CoA
      to the amino-terminal Gly residue of cellular proteins. Product inhibition
      studies indicate that Nmt1p has an ordered Bi Bi reaction mechanism with
      myristoyl-CoA binding to the apo-enzyme to form a high affinity binary complex
      followed by binding of peptide with subsequent release of CoA and then the
      myristoylpeptide product. We have used isothermal titration calorimetry to
      quantify the effects of varying acyl chain length and removing the 3'-phosphate
      group of CoA on the energetics of interaction between Nmt1p and acyl-CoA ligands.
      Myristoyl-CoA binds to apo-Nmt1p with an affinity of 15 nM, corresponding to a
      binding free energy of -10.9 kcal/mol. This free energy is composed of a large
      favorable enthalpy of -24 kcal/mol and a large unfavorable entropic term. This
      large negative delta H degrees is consistent with a conformational change in the
      enzyme upon ligation, allowing synthesis of a functional peptide binding site.
      Binding of palmitoyl-CoA and lauroyl-CoA is driven by an exothermic enthalpy
      change which is much smaller than the corresponding parameter for myristoyl-CoA
      binding. The large differences in binding enthalpy and entropy (delta delta H
      degrees and T delta delta S degrees = 8-9 kcal/mol) demonstrate that the "off
      length" acyl-CoAs bind to Nmt1p in a significantly different energetic fashion
      from myristoyl-CoA, even though the enzyme does not have a great deal of
      specificity among these ligands in terms of binding free energy (delta delta G
      degrees < or = 1 kcal/mol). The effect of removing the CoA 3'-phosphate group
      from myristoyl-CoA is similar to the effect of a two-carbon change in acyl chain
      length: i.e. an enthalpy dominated reduction in binding affinity. However,
      kinetic studies reveal that removing the 3'-phosphate from myristoyl-CoA has
      little effect on Nmt1p's catalytic efficiency, indicating that the 3'-phosphate
      group contributes binding free energy but little catalytic destabilization. The
      greater delta delta G degrees, with smaller delta delta H degrees and delta delta
      S degrees components, produced by removing the 3'-phosphate compared to
      increasing chain length suggests that it is not primarily the interactions of the
      3'-phosphate which are disrupted when palmitoyl-CoA is substituted for myristoyl
      CoA. No detectable interactions were noted between apo-Nmt1p and the substrate
      peptide, GAAPSKIV-NH2, providing additional support for the preferred ordered
      reaction mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8157631
TI  - Mutagenic studies of the interaction between the aspartate receptor and
      methyltransferase from Escherichia coli.
AB  - The 4 glutamate residues that are the sites of methylation in the aspartate
      receptor, which mediates bacterial chemotaxis, were systematically mutated to
      aspartate residues. None of the aspartate residues were methylated. In each case,
      the presence of the aspartate mutations altered the methylation rates at
      glutamate residues on the same receptor. Methylation was nearly eliminated at
      residues two turns of alpha helix, in the N-terminal direction, from a site of
      mutation, whereas less severe changes occurred at other positions. The
      methyltransferase apparently must contact a glutamate or glutamine residue two
      turns of helix in the C-terminal direction from the site of modification in order
      to methylate that position at a maximal rate. Mutations from glutamate to
      aspartate at any of the four sites also appear to alter the methylation rate at
      the other sites through a change in the structure of the receptor. The aspartate
      mutations did not substantially alter the affinity of the methyltransferase for
      the receptor.

PMID- 8157632
TI  - Reduction of disulfide bonds in sarcoplasmic reticulum Ca(2+)-ATPase by
      dithiothreitol causes inhibition of phosphoenzyme isomerization in catalytic
      cycle. This reduction requires binding of both purine nucleotide and Ca2+ to
      enzyme.
AB  - Sarcoplasmic reticulum vesicles were treated with 6 mM dithiothreitol in the
      presence of 2 mM ATP and 0.1 mM Ca2+ at 25 degrees C and pH 7.0 for various
      periods. The Ca(2+)-ATPase was inhibited almost completely in 100 min. The
      content of the sulfhydryl group, which was measured in 2.5% SDS with 5,5'
      dithiobis(2-nitrobenzoic acid), increased during the treatment. Extrapolation of
      the plot of the Ca(2+)-ATPase activity versus the increment of the sulfhydryl
      group showed that reduction of two disulfide bonds per phosphorylation site leads
      to a complete inhibition of the enzyme. This reduction required binding of both
      Ca2+ (with a high affinity) and a purine nucleotide to the enzyme. Adenosine 5'
      (beta,gamma-methylene) triphosphate (a nonhydrolyzable ATP analog) was also
      effective for the reduction, while phosphorylation of the enzyme with acetyl
      phosphate or P(i) did not trigger the reduction. These results indicate that
      formation of a substrate-enzyme-calcium complex is responsible for the
      dithiothreitol-induced disulfide bond reduction. The partial reactions of the
      Ca(2+)-ATPase were examined with the vesicles that had been treated with
      dithiothreitol in the presence of ATP and Ca2+ for 100-200 min. Neither
      isomerization of the unphosphorylated enzyme from the low Ca2+ affinity form to
      the high Ca2+ affinity form nor phosphorylation of the enzyme with ATP or P(i)
      was inhibited. In contrast, isomerization of the phosphoenzyme intermediate from
      the ADP-sensitive form to the ADP-insensitive form was strongly inhibited. These
      results show that the observed inhibition of the Ca(2+)-ATPase is due to a
      selective blockage of the phosphoenzyme isomerization.

PMID- 8157633
TI  - A reverse gyrase with an unusual structure. A type I DNA topoisomerase from the
      hyperthermophile Methanopyrus kandleri is a two-subunit protein.
AB  - Reverse gyrase, an ATP-dependent topoisomerase that positively supercoils DNA,
      has been purified to near-homogeneity from the hyperthermophile Methanopyrus
      kandleri. It migrates on SDS-polyacrylamide gel electrophoresis as two principal
      bands with apparent molecular masses of 150 and 50 kDa. Both proteins remain
      associated throughout all chromatographic steps. Transfer of a radioactive
      phosphate from DNA to the 50-kDa protein and gel retardation experiments indicate
      that this protein forms the covalent complex with DNA. A blot overlay assay
      identifies the 150-kDa protein as the potential ATPase. This is the first
      evidence that a reverse gyrase can be a topoisomerase consisting of two
      protomers. In analogy with the DNA gyrase A subunit (DNA breakage and reunion
      activity) and the B subunit (ATPase), the 50- and 150-kDa components of Mka
      reverse gyrase have been designated the A and B subunits, respectively.
      Methanopyrus reverse gyrase changes DNA linking number in steps of one and its A
      subunit covalently binds to the 5'-DNA phosphoryl group. It nicks DNA at sites
      that predominantly have a cytosine at the -4-position. The same rule was derived
      previously for monomeric reverse gyrase from sulfur-metabolizing
      hyperthermophiles and for topoisomerase I from mesophilic bacteria. Based on
      these results, Mka reverse gyrase is classified as belonging to group A of type I
      topoisomerases. The structural diversity of type I group A topoisomerases
      parallels the diversity of type II enzymes and suggests the evolution of an
      essential function by gene fusion.

PMID- 8157634
TI  - Phospholipids of Rhizobium contain nodE-determined highly unsaturated fatty acid
      moieties.
AB  - In Rhizobium leguminosarum the nodABC and nod-FEL operons are involved in the
      production of lipooligosaccharide signals, which mediate host specificity. A nodE
      determined highly unsaturated C18:4 fatty acid (trans-2,trans-4,trans-6,cis-11
      octadecatetraenoic acid) is essential for the ability of the signals to induce
      nodule primordia (Spaink, H. P., Sheeley, D. M., van Brussel, A. A. N., Glushka,
      J., York, W.S., Tak, T., Geiger, O., Kennedy, E. P., Reinhold, V. N., and
      Lugtenberg, B. J. J. (1991) Nature 354, 125-130) and preinfection thread
      structures (van Brussel, A. A. N., Bakhuizen, R., van Spronsen, P. C., Spaink, H.
      P., Tak, T., Lugtenberg, B. J. J., and Kijne, J. W. (1992) Science 257, 70-72) on
      the host plant Vicia sativa. We presently focus on the question of how these lipo
      oligosaccharide signals are synthesized in Rhizobium. Here we show that after the
      induction of the nodFE genes, even in the absence of the nodABC genes, the trans
      2,trans-4,trans-6,cis-11-octadecatetraenoic acid, which has a characteristic
      absorbance maximum of 303 nm, is synthesized; this shows that the biosynthesis of
      the unusual fatty acid is not dependent on the synthesis of the
      lipooligosaccharides. This finding also suggests that the biosynthesis of the
      unusual fatty acid is completed before it is linked to the sugar backbone of the
      lipooligosaccharide. In an attempt to identify the lipid fraction with which the
      unusual C18:4 fatty acid is associated, we found that it is linked to the sn-2
      position of the phospholipids. Even when lipooligosaccharide signals are produced
      in a wild type Rhizobium cell, a fraction of the unusual fatty acid is still
      bound to all major phospholipids. These findings offer interesting possibilities.
      1) The phospholipids might be biosynthetic intermediates for the synthesis of
      lipooligosaccharide signals, and 2) phospholipids, containing nodFE-derived fatty
      acids, might have a signal function of their own.

PMID- 8157635
TI  - Isolation and sequencing of insecticidal peptides from the primitive hunting
      spider, Plectreurys tristis (Simon).
AB  - About 50 peptide toxins were purified from venom of the primitive hunting spider,
      Plectreurys tristis. Bioassay by injection into larval Heliothis virescens
      (tobacco budworm) allowed selection of nine toxins for analysis of amino acid
      sequences. Total sequences were determined for six of the more insecticidal
      peptides (46-49 amino acids) and three contained free carboxyl-terminal amino
      acids. These toxins (plectoxins) are paralytic and/or lethal when injected into
      insect pests such as the lepidopterous larvae H. virescens, Spodoptera exigua
      (beet armyworm), and Manduca sexta (tobacco hornworm). We expect these plectoxins
      to be useful in insect control after delivery by a suitable agent such as a
      recombinant baculovirus.

PMID- 8157636
TI  - Probing the retinol-binding site of bovine beta-lactoglobulin.
AB  - The retinol-binding site of beta-lactoglobulin has been located by selective
      modification of amino acid residues which reside in the two putative binding
      sites. Based upon two separate crystallographic analyses of bovine beta
      lactoglobulin, different binding sites for retinol have been proposed: one
      proposal favors an interior cavity, the other a surface cleft. To discriminate
      between these two models, we have made four separate site-directed mutations
      introducing a W19A or a K70M in the interior pocket and a F136A or K141M in the
      surface pocket. The K70M beta-lactoglobulin exhibited a marked decrease in its
      binding of retinoic acid compared to the F136A, K141M, and wild-type proteins.
      Retinyldenepropylamine, a retinyl Schiff base analog of retinol, was synthesized
      and its absorption spectrum when bound to the wild-type, K70M, and K141M proteins
      was examined to probe its interaction with the respective lysine residues. The
      retinylidenepropylamine bound in the K70M beta-lactoglobulin exhibited a kinetic
      red shift as distinct from the blue shift observed when it is bound to either the
      K141M or wild-type beta-lactoglobulins. The blue shift indicates protonation of
      the Schiff base. The resulting tagged peptide was isolated after cyanogen bromide
      cleavage and found to be the Ala25-Met107 peptide, consistent with the Lys70
      being the residue which interacts with the bound retinol. These results support
      the proposal that retinol binds to an evolutionarily conserved interior cavity
      rather than the surface pocket.

PMID- 8157637
TI  - Mutational analysis of the metal sites in an LIM domain.
AB  - Site-directed mutagenesis was carried out to map the residues that form the two
      Zn(II) sites within a LIM domain. The C-terminal LIM domain derived from the
      cysteine-rich protein was utilized for this analysis and is referred to as LIM2.
      Seven cysteinyl residues and a single histidyl residue in the LIM2 sequence,
      CX2CX17HX2CX2CX2CX17CX2C, comprise the conserved residues in the LIM consensus
      that are potential Zn(II) ligands. Two Zn(II) binding sites exhibiting
      tetrathiolate (S4) and S3N1 Zn(II) coordination are displayed by LIM2 (Kosa, J.
      L., Michelsen, J. W., Louis, H. A., Olsen, J. I., Davis, D. R., Beckerle, M. C.,
      and Winge, D. R. (1994) Biochemistry 33, 468-477). Site-directed mutagenesis was
      employed to generate three mutant LIM2 proteins with conversions of the second
      conserved cysteine to histidine (C2H), the fifth conserved cysteine to histidine
      (C5H), and the last conserved cysteine to aspartate (C8D). Metal coordination by
      the mutant proteins was evaluated by atomic absorption spectroscopy, Co(II)
      electronic spectroscopy, and 113Cd NMR spectroscopy. The results permit
      discrimination between various models of metal ion binding and suggest that the
      LIM domain is comprised of a S3N1 site generated from the four N-terminal
      candidate ligands (CX2CX17HX2C) and a S4 site generated from the four C-terminal
      candidate ligands (CX2CX17CX2C).

PMID- 8157638
TI  - Beta-elimination of phosphate from reaction intermediates by site-directed
      mutants of ribulose-bisphosphate carboxylase/oxygenase.
AB  - Five residues (Thr-53, Asn-54, Gly-370, Gly-393, and Gly-394) of Rhodospirillum
      rubrum ribulose-bisphosphate carboxylase/oxygenase are positioned to serve as
      hydrogen-bond donors for the C1 phosphate of ribulose bisphosphate and thereby
      constrain conformational flexibility of the initial enediol(ate) intermediate
      (Knight, S., Andersson, I., and Branden, C.-I. (1990) J. Mol. Biol. 215, 113
      160). To study the functional contributions of the residues implicated in
      ribulose bisphosphate binding and intermediate stabilization, we have replaced
      them individually with alanine, either to remove the H-bonding group (T53A, N54A)
      or to introduce bulk (G370A, G393A, G394A). Consequences of substitutions include
      diminution of carboxylase activity (with a lesser impact on enolization
      activity), increase of Km (ribulose bisphosphate), and decrease of carboxylation:
      oxygenation specificity. During catalytic turnover of ribulose bisphosphate by
      several mutants, substantial amounts of the substrate are diverted to 1-deoxy-D
      glycero-2,3-pentodiulose 5-phosphate, reflecting beta-elimination of phosphate
      from the enediol(ate) intermediate. This side product is not observed with wild
      type enzyme, nor has it been reported with mutant enzymes characterized
      previously. Another consequence of disruption of the phosphate binding site is
      enhanced production of pyruvate, relative to wild-type enzyme, by some of the
      mutants due to decomposition of the acicarbanion of 3-phosphoglycerate (the
      terminal intermediate). These data provide direct evidence that phosphate ligands
      stabilize conformations of intermediates that favor productive turnover and
      mitigate beta-elimination at two stages of overall catalysis.

PMID- 8157639
TI  - Recombinant replication protein A: expression, complex formation, and functional
      characterization.
AB  - Replication protein A (RPA) is a multisubunit, single-stranded DNA-binding
      protein that is absolutely required for replication of SV40 DNA. The three cDNAs
      encoding the subunits of human replication protein A (70, 32, and 14 kDa) have
      been expressed individually and in combination in Escherichia coli. When subunits
      were expressed individually, appropriately sized polypeptides were synthesized,
      but were found to be either insoluble or aggregated with other proteins. We
      examined the interactions between individual RPA subunits by expressing pairs of
      subunits and determining if they formed stable complexes. Only the 32- and 14-kDa
      subunits formed a soluble complex when coexpressed. This complex was purified and
      characterized. The 32-14 kDa subcomplex did not have any effect on DNA
      replication and was not phosphorylated efficiently in vitro. We believe that the
      32.14-kDa subcomplex may be a precursor in the assembly of the complete RPA
      complex. Coexpression of all three subunits of RPA resulted in a significant
      portion of each polypeptide forming a soluble complex. We have purified
      recombinant RPA complex from E. coli and demonstrated that it has properties
      similar to those of human RPA. Recombinant human RPA has the same subunit
      composition and the same activities as the authentic complex from human cells.
      Recombinant human RPA binds single-stranded DNA and is capable of supporting SV40
      DNA replication in vitro. In addition, recombinant RPA became phosphorylated when
      incubated under replication conditions.

PMID- 8157640
TI  - Glycosphingolipid receptor function is modified by fatty acid content. Verotoxin
      1 and verotoxin 2c preferentially recognize different globotriaosyl ceramide
      fatty acid homologues.
AB  - Verotoxins (VT) are a family of Escherichia coli-derived toxins which have been
      associated with hemolytic uremic syndrome, the leading cause of acute pediatric
      renal failure, and hemorrhagic colitis. Verotoxins (VT1 and VT2c) both show
      terminal gal alpha 1-4gal-dependent binding to globotriaosylceramide (Gal alpha 1
      4Gal beta 1-4Glc-Cer; Gb3), yet VT2c shows a thousandfold lower specific
      cytotoxic activity in vitro. Our previous studies have shown this discrepancy is
      a function of the receptor binding B subunit and that VT1/Gb3 binding in a lipid
      matrix is affected by heterogeneity in the ceramide fatty acid chain length. The
      influence of the fatty acid composition of Gb3 on the binding of VT1 and VT2c has
      now been compared using 14 homogeneous semisynthetic Gb3 molecular species of
      differing fatty acid chain length and degree of saturation from C12 to C24. The
      binding of verotoxin was quantitated by Scatchard analysis using a solid-phase
      binding assay in the presence of auxiliary lipids, which may in some respects
      approximate to receptor function within the plasma membrane of sensitive cells.
      Differential binding was observed for several of these species in the lipid
      matrix, indicating that the fatty acid moiety of Gb3 is important for VT binding
      under such conditions. The short chain fatty acid containing Gb3 (C12 and C14)
      showed minimal binding. Middle and long chain fatty acid Gb3 homologues (C16,
      C18, C20, C22, and C24) were effectively recognized by VTs. The presence of an
      unsaturated fatty acid in Gb3 significantly increased VT binding in all cases.
      C20:0 and C22:1 containing Gb3 had the greatest capacity to bind VT1. In
      contrast, C18:0 and C18:1 homologues showed the greatest capacity for VT2c
      binding (higher than VT1). These results were, in general, reflected in cell
      cytotoxicity in that receptor-deficient cells reconstituted with C22:1Gb3 were
      maximally sensitive to VT1 in vitro whereas cells reconstituted with C18:1Gb3
      were maximally sensitive to VT2c. VT2c was an ineffective inhibitor of 125I-VT1
      binding to C22:1 Gb3 but in contrast, more effective than VT1 to compete binding
      to C18:1 Gb3. Similarly, VT1 was less effective than VT2c to compete binding of
      125I-VT2c to C18:1 but more effective than VT2c to compete for C22:1 Gb3 binding.
      These results suggest that VT1 and VT2c bind selectively to different but
      overlapping carbohydrate epitopes on the Gb3 molecule which are differentially
      available in these Gb3 fatty acid homologues in a lipid environment.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8157641
TI  - Measurements of ATP binding on the large cytoplasmic loop of the sarcoplasmic
      reticulum Ca(2+)-ATPase overexpressed in Escherichia coli.
AB  - The large cytoplasmic loop of the sarcoplasmic reticulum Ca(2+)-ATPase (LCL),
      situated between Lys329 and Phe740, is believed to contain both its
      phosphorylation and ATP binding domains. A cDNA fragment coding for this amino
      acid sequence was generated in vitro and cloned in vector pQE8 which allowed the
      overexpression in Escherichia coli of this Ca(2+)-ATPase domain fused with a
      cluster of 6 histidines at its NH2 terminus. The fusion protein produced in an
      insoluble form within bacteria was solubilized in 4 M urea, purified on
      immobilized Ni2+, and then renatured by elimination of urea. More than 4 mg of
      purified renatured fusion protein was obtained from 500 ml of culture. ATP
      binding on the refolded protein was demonstrated by two methods: 1) detection of
      ATP-induced intrinsic fluorescence change and 2) binding of the fluorescent ATP
      analogue 2',3'-O-(2,4,6-trinitrophenyl)-adenosine-5'-triphosphate (TNP-ATP) and
      its chase by ATP. It is shown that the LCL protein has one single TNP-ATP binding
      site having a dissociation constant (Kd) of 1.6-1.9 microM. Both methods yielded
      a Kd for ATP around 200 microM. Binding of other nucleotides was detected with a
      sequence of Kd identical to that found for native Ca(2+)-ATPase: ATP < ADP < GTP
      < AMP < ITP. A Mg2+ binding site was also found on the LCL protein (Kd = 100
      microM at pH 7.2). The fluorescence of bound TNP-ATP was found to be highly
      dependent on Mg2+ binding on this site.

PMID- 8157642
TI  - Characterization of the protein-protein interactions determining the heat shock
      protein (hsp90.hsp70.hsp56) heterocomplex.
AB  - We have reported previously that the three heat shock proteins hsp56, hsp70, and
      hsp90 exist together in a heterocomplex in human lymphocyte cytosol (Sanchez, E.
      R., Faber, L. E., Henzel, W. J., and Pratt, W. B. (1990) Biochemistry 29, 5145
      5152). All three of these proteins also exist in the native glucocorticoid
      receptor heterocomplex isolated from WCL2 cell cytosol and we have recently shown
      that the three heat shock proteins are present when immunopurified mouse
      glucocorticoid receptor is reconstituted into a heterocomplex by rabbit
      reticulocyte lysate (Hutchison, K. A., Scherrer, L. C., Czar, M. J., Ning, Y.,
      Sanchez, E. R., Leach, K. L., Deibel, M. R., Jr., and Pratt, W. B. (1993)
      Biochemistry 32, 3953-3957). In this work, we show that highly purified mouse
      hsp90 binds in a reversible equilibrium to immunopurified rabbit hsp56, but hsp56
      does not bind to purified mouse hsp70. In contrast to the equilibrium binding of
      hsp90 to hsp56, purified hsp90 binds poorly or not at all to purified hsp70
      unless a third factor from reticulocyte lysate is present to permit complex
      formation. This hsp70.hsp90 complex-forming factor is heat-labile, and in the
      presence of this factor and ATP, a heat shock protein heterocomplex can be
      reconstituted from purified mouse hsp90 and hsp70 and rabbit hsp56 that is
      present in the factor preparation. Our data are consistent with a model in which
      hsp56 and hsp70 bind to different sites on hsp90 but do not interact with each
      other. The presence of hsp56 in the heat shock protein heterocomplex is not
      stabilized by molybdate but hsp56 is stabilized if the glucocorticoid receptor is
      present in addition to hsp90 and hsp70.

PMID- 8157643
TI  - Lipooligosaccharide biosynthesis in pathogenic Neisseria. Cloning,
      identification, and characterization of the phosphoglucomutase gene.
AB  - The lipooligosaccharide (LOS) of pathogenic Neisseria is an important factor in
      disease pathogenesis. Little is known about the genes involved in neisserial LOS
      biosynthesis. To elucidate specific LOS biosynthetic genes, we screened a Tn916
      library that was constructed in Neisseria meningitidis strain NMB. This strain
      expresses a single LOS that has an molecular mass of 4.5 kDa and binds monoclonal
      antibody (mAb) 3F11. This library was screened using a mAb panel that recognizes
      structural differences in neisserial LOS oligosaccharides. A stable LOS mutant of
      strain NMB was identified which we designated NMB-R6. This mutant expressed an
      LOS with an molecular mass of approximately 3.1-3.2 kDa and did not bind mAb
      3F11. Genomic DNA from this mutant transformed N. meningitidis strain NMB to the
      tetracycline resistant NMB-R6 phenotype greater than 10(-4)/recipient/micrograms
      of DNA. In addition, we transformed Neisseria gonorrhoeae strain 1291 (LOS
      phenotype molecular mass 4.5 kDa, mAb 3F11+) to the NMB-R6 LOS phenotype with N.
      meningitidis NMB-R6 genomic DNA. Analysis of N. gonorrhoeae strain 1291-R6 LOS by
      mass spectroscopy showed that the LOS oligosaccharide structure is GlcNAc-
      >Hep2phosphoethanolamine-->2-keto-3-deoxymannooctuloson ic acid (where Hep is
      heptose). Sequence analysis showed that the transposon is inserted into the 3'
      end of a gene that has homology to the human phosphoglucomutase (PGM) gene.
      Sequence comparison indicated that the putative PGM gene in N. gonorrhoeae 1291
      and N. meningitidis NMB had 92% identity at the DNA level. PGM and glucokinase
      activity was present in cell free extracts of N. meningitidis NMB and N.
      gonorrhoeae strain 1291. N. meningitidis NMB-R6 and N. gonorrhoeae strain 1291-R6
      had no detectable PGM activity, whereas glucokinase activity was similar to the
      wild type strains. PGM activity can be reconstituted in N. meningitidis strain
      NMB-R6 by transformation with the cloned PGM gene. SDS-polyacrylamide gel
      electrophoresis demonstrated that NMB-R6 transformed with the PGM gene expressed
      the 3F11+, 4.5-kDa LOS of the parent NMB strain. The inability of N. meningitidis
      NMB-R6 and N. gonorrhoeae strain 1291-R6 to convert glucose 6-phosphate to
      glucose 1-phosphate results in the truncated LOS phenotype expressed by these
      mutants.

PMID- 8157644
TI  - Mutational analysis of the substrate binding pockets of the Rous sarcoma virus
      and human immunodeficiency virus-1 proteases.
AB  - Mutations, designed by analysis of the crystal structures of Rous sarcoma virus
      (RSV) and human immunodeficiency virus type 1 (HIV-1) protease (PR), were
      introduced into the substrate binding pocket of RSV PR. The mutations substituted
      nonconserved residues of RSV PR, located within 10 A of the substrate, for those
      in structurally equivalent positions of HIV-1 PR. Changes in the activity of
      purified mutants were detected in vitro by following cleavage of synthetic
      peptides representing wild-type and modified RSV and HIV-1 gag and pol
      polyprotein cleavage sites. Substituting threonine for valine 104 (V104T), S107N,
      I44V, Q63M or deletion of residues 61-63 produced enzymes that were 2.5-7-fold
      more active than the wild type RSV PR. Substituting I42D, M73V, and A100L
      produced enzymes with lower activity, whereas a mutant that included both M73V
      and A100L was as active as wild type. Several substitutions altered the
      specificity for substrate. These include I42D and I44V, which contribute to the
      S2 and S2' subsites. These proteins exhibited HIV-1 PR specificity for P2- or P2'
      modified peptide substrates but unchanged specificity with P4-, P3-, P1-, P1'-,
      and P3'-modified substrates. Changes in specificity in the S4 subsite were
      detected by deletion of residues 61-63. These results confirm the hypothesis that
      the subsites of the substrate binding pocket of the retroviral protease are
      capable of acting independently in the selection of substrate amino acids.

PMID- 8157645
TI  - Functional expression and site-directed mutagenesis of a synthetic gene for alpha
      bungarotoxin.
AB  - In order to explore the structure-function relationships of the curare mimetic
      alpha-neurotoxins we have constructed and cloned a synthetic gene for Bungarus
      multicinctus alpha-bungarotoxin which is expressed in Escherichia coli. The
      recombinant alpha-bungarotoxin is expressed as a fusion protein with alpha
      bungarotoxin linked to the COOH-terminal end of the T7 Gene 9-encoded coat
      protein. After treatment of the fusion protein with Factor Xa protease, a
      recombinant alpha-bungarotoxin is released that co-migrates with authentic alpha
      bungarotoxin upon reverse-phase high performance liquid chromatography and ion
      exchange chromatography. Final yields of active recombinant alpha-bungarotoxin
      were about 0.4 mg/liter of starting bacterial culture. The recombinant alpha
      bungarotoxin contains 10 additional residues linked to the NH2-terminal Ile of
      the alpha-bungarotoxin sequence due apparently to the inaccessibility of the
      engineered cleavage site to Factor Xa. Nevertheless, the recombinant alpha
      bungarotoxin is capable of binding to the nicotinic acetylcholine receptor with
      an apparent affinity that is only decreased approximately 1.7-fold from that of
      authentic alpha-bungarotoxin. Alanine substitution of a residue, Asp30, highly
      conserved among alpha-neurotoxins and previously suggested to play a key role in
      receptor recognition, resulted in a recombinant alpha-bungarotoxin whose receptor
      binding activity is indistinguishable from authentic alpha-bungarotoxin.

PMID- 8157646
TI  - A peptide encoding the c-Jun delta domain inhibits the activity of a c-jun amino
      terminal protein kinase.
AB  - Evidence suggests that the c-Jun protooncogene delta (delta) domain (amino acids
      31-60) helps regulate the transcriptional activating capacity of c-Jun by
      modulating the amino-terminal phosphorylation of this protein. By using a peptide
      encoding the delta domain and purified amino-terminal c-Jun protein kinase, we
      demonstrate that the delta domain peptide inhibits phosphorylation of the amino
      terminus of both c-Jun and the related protein JunD. The delta domain peptide
      inhibited the activation of the c-Jun amino-terminal protein kinase by phorbol
      esters in permeabilized U937 leukemic cells. Mutation of c-Jun followed by
      transfection into U937 leukemic cells demonstrated that partial deletions of the
      delta domain are sufficient to block phosphorylation of the amino terminus of c
      Jun. In vitro deletion of the amino-terminal (amino acids 31-44) half of the
      delta domain inhibited the phosphorylation of c-Jun. However, deletion of the
      carboxyl-terminal (amino acids 45-60) half only partially inhibited c-Jun
      phosphorylation. Therefore, these results indicate that the delta domain sequence
      is an important regulator of c-Jun amino-terminal phosphorylation.

PMID- 8157647
TI  - Regulation of carboxypeptidase E. Effect of Ca2+ on enzyme activity and
      stability.
AB  - Carboxypeptidase E (CPE), an enzyme that functions in the post-translational
      processing of bioactive peptides, is a member of the metallocarboxypeptidase gene
      family. A 12-residue region of CPE has 70% amino acid identity with the bacterial
      enzyme carboxypeptidase T (CPT); in CPT, this region has been identified
      previously as the Ca(2+)-binding region (Teplyakov, A., Polyakov, K., Obmolova,
      G., Strokopytov, B., Kuranova, I., Osterman, A., Grishin, N., Smulevitch, S.,
      Zagnitko, O., Galperina, O., Matz, M., and Stepanov, V. (1992) Eur. J. Biochem.
      208, 281-288). Using 45Ca2+ binding, we determined that CPE binds Ca2+. To
      investigate the potential function for the interaction of CPE with Ca2+, we
      investigated the effect of Ca2+ on aggregation, thermostability, and enzyme
      activity of CPE. CPE does not aggregate under a variety of Ca2+ concentrations at
      either pH 5.5 or 7.5, and with protein concentrations ranging from 10 to 100
      micrograms/ml. Whereas Ca2+ generally stabilizes proteins to thermal
      denaturation, CPE was destabilized by Ca2+ and stabilized by low concentrations
      of EGTA. The Ca(2+)-induced destabilization of CPE was more pronounced at pH 8
      than at lower pH values. At pH 8, CPE was unstable even at 37 degrees C, with
      approximately 40% loss of activity upon incubation for 30 min in the absence of
      added Ca2+ and 70% loss of activity upon incubation in the presence of 10 mM
      CaCl2. Enzyme activity was not influenced by added Ca2+, but was stimulated by
      micromolar concentrations of EGTA; kinetic analysis showed this stimulation to be
      due to a change in Vmax, and not Km. Taken together, these data suggest that Ca2+
      plays a role in the regulation of CPE activity.

PMID- 8157648
TI  - Identical mutations at corresponding positions in two homologous proteins with
      nonidentical effects.
AB  - The x-ray structure of a mutant (Gly72 to Asp) of the Escherichia coli ribose
      binding protein with altered transport function has been solved and refined to
      2.2-A resolution with a conventional R-factor (R-factor = [formula: see text]) of
      16.0% and good stereochemistry. Comparison with the wild type ribose-binding
      protein shows that the structure is disturbed little at the actual mutation site,
      but quite appreciably in a neighboring loop. Changes in the surface of the
      protein at the site of mutation, however, seem to explain the functional effects.
      A corresponding mutation of the related glucose/galactose-binding protein has
      different structural and functional effects due to the different structural
      context of the mutation site in that protein. These results are consistent with
      the concept that these proteins have slightly different ways of interacting with
      the membrane components in transport and chemotaxis.

PMID- 8157649
TI  - Yeast squalene synthase. A mechanism for addition of substrates and activation by
      NADPH.
AB  - Squalene synthase catalyzes the condensation of two molecules of farnesyl
      diphosphate (FPP) to give presqualene diphosphate (PSPP) and the subsequent
      reductive rearrangement of PSPP to squalene. Previous studies of the mechanism of
      addition of FPP to the enzyme have led to conflicting interpretations of initial
      velocity measurements (Beytia, E., Qureshi, A. A., and Porter, J.W. (1973) J.
      Biol. Chem. 248, 1856-1867; Agnew, W.S., and Popjak, G. (1978) J. Biol. Chem.
      253, 4566-4573). Initial velocities for synthesis of PSPP and squalene were
      measured over a wider range of FPP and NADPH concentrations than previously
      reported, using a soluble form of recombinant enzyme. In the absence of NADPH,
      PSPP formation was activated by FPP at concentrations above approximately 0.5
      microM. At fixed levels of NADPH, the dependence of initial rates of PSPP and
      squalene synthesis on FPP concentrations indicated that the C15 substrate added
      by a sequential mechanism. In addition, NADPH stimulated synthesis of PSPP by 40
      fold at saturating levels of the cofactor. This stimulation is, at least in part,
      by reduction of PSPP to squalene.

PMID- 8157650
TI  - Liver heparan sulfate structure. A novel molecular design.
AB  - The structure of rat liver heparan sulfate (HS) has been investigated using a
      combination of (a) chain scission with specific reagents, (b) disaccharide
      compositional analysis, and (c) end-referenced sequence analysis of the proximal,
      protein-linked region of the chain. This study reveals that the liver synthesizes
      a highly sulfated HS species (1.34 sulfates/disaccharide), particularly high in N
      sulfation (60%) and 2-O-sulfate content (36%). Approximately half of the latter
      is found in trisulfated disaccharides, i.e. IdceA(2-OSO3) alpha 1-4GlcNSO3 (6
      OSO3). End-referencing methodology established the existence of an extended,
      unmodified heparan (GlcUA beta 1-4GlcNAc) sequence, 8-11 disaccharides in length,
      attached to the linkage tetrasaccharide, similar to that found in a number of
      other HS species. Directly following this is a mixed HexUA1-4GlcNR(6-OSO3) (where
      GlcNR represents alpha-D-glucosamine with an unspecified N-substituent)
      containing sequence of variable length, culminating in the appearance of the
      first IdceA(2-OSO3) residue approximately 20 disaccharides from the linkage
      region, i.e. approximately 40% along the length of the chain. The distal 60% of
      the polysaccharide is highly sulfated (approximately 2 sulfates/disaccharide) and
      mainly comprises three heparin-like domains, highly enriched in IdceA(2-OSO3)
      residues. Overall, liver HS qualifies as an extreme member of the HS family, with
      a considerable proportion of heparin-like structure asymmetrically concentrated
      to the distal part of the chain.

PMID- 8157651
TI  - Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the
      major heparan sulfate structural determinants.
AB  - We have demonstrated by affinity chromatography that hepatocyte growth factor
      (HGF) binds strongly to heparan sulfate (HS). This substantiates previous
      suggestions that cell-surface heparan sulfate proteoglycans constitute the so
      called low affinity cellular binding sites for HGF. Using a recombinant human HGF
      affinity column, we have analyzed the effects of various specific chemical and
      enzymatic modifications/depolymerizations of HS on its affinity in order to
      elucidate the polysaccharide structural determinants. Interaction is shown to be
      only slightly affected by digestion with heparinase I or III or by replacement of
      N-sulfates with N-acetyl groups. This suggests a specific role for sulfated
      domains containing nonsulfated IdceA residues, with only a small contribution
      from N-sulfates and IdceA(2-OSO3) residues. In addition, disaccharide analyses of
      various HGF-binding oligosaccharides indicate that affinity is more closely
      associated with 6-O-sulfation of GlcNSO3 residues than with sulfation at any
      other position. Although interaction can be demonstrated with heparinase III
      resistant oligosaccharides as small as hexasaccharides, the highest affinity was
      found with oligosaccharides containing a minimum of 10-12 monosaccharides. The
      structural specificity of the HGF-HS interaction is thus shown to be radically
      different from that previously described for the basic fibroblast growth factor
      HS interaction.

PMID- 8157652
TI  - Site of fasciculin interaction with acetylcholinesterase.
AB  - Fasciculin, a 6750-Da peptide from the venom of Dendroaspis, is known to inhibit
      reversibly mammalian and fish acetylcholinesterases at picomolar concentrations,
      but is a relatively weak inhibitor of avian, reptile, and insect
      acetylcholinesterases and mammalian butyryl-cholinesterases. An examination of
      fasciculin association with several mutant forms of recombinant DNA-derived
      acetylcholinesterase from mouse shows that it interacts with a cluster of
      residues near the rim of the gorge on the enzyme. The aromatic residues, Trp286,
      Tyr72, and Tyr124, have the most marked influence on fasciculin binding, whereas
      Asp74, a charged residue in the vicinity of the binding site that affects the
      binding of low molecular weight inhibitors, has little influence on fasciculin
      binding. The 3 aromatic residues are unique to the susceptible
      acetylcholinesterases and, along with Asp74, constitute part of the peripheral
      anionic site. Fasciculin falls in the family of three-loop toxins that include
      the receptor blocking alpha-toxins and cardiotoxins. From this basic structural
      motif, a binding site has evolved on fasciculin to be highly specific for the
      peripheral site on acetylcholinesterase. Acetylthiocholine affects rates of
      fasciculin binding at concentrations causing substrate inhibition. In the case of
      the mutant cholinesterases where rates of fasciculin dissociation are more rapid,
      steady state kinetic parameters also show acetylthiocholine-fasciculin
      competition to be consistent with occupation at a peripheral or substrate
      inhibition site rather than the active center.

PMID- 8157653
TI  - Kinetic mechanism of phosphate/phosphate and phosphate/OH- antiports catalyzed by
      reconstituted phosphate carrier from beef heart mitochondria.
AB  - In an optimized reconstituted system, the basic kinetic properties of the
      phosphate carrier from bovine heart mitochondria, e.g. the influence of membrane
      potential, pH, and proton gradient, were investigated for the two physiological
      modes of transport (Pi-/Pi- antiport and electroneutral, unidirectional phosphate
      transport). On the basis of these data, which closely resemble the function known
      from mitochondria, the reaction mechanism of the phosphate carrier was determined
      using bireactant initial velocity studies in both transport modes. Translocation
      occurred according to a simultaneous (sequential) mechanism, involving a ternary
      complex in transport catalysis. This mechanism indicates that the phosphate
      carrier falls into the same functional family as most other mitochondrial
      carriers. A detailed analysis of the different effects of pH on transport
      substrates and carrier protein in both possible transport modes, in combination
      with the identity of the kinetic mechanism in both modes, provides evidence that
      the unidirectional phosphate transport is catalyzed by Pi-/OH- antiport rather
      than by Pi-/H+ symport. We furthermore observed noncompetitive inhibition of
      phosphate transport by other anions. The consequences of this result with respect
      to a functional model of the carrier protein are discussed.

PMID- 8157654
TI  - Thimerosal potentiates Ca2+ release mediated by both the inositol 1,4,5
      trisphosphate and the ryanodine receptors in sea urchin eggs. Implications for
      mechanistic studies on Ca2+ signaling.
AB  - Two intracellular Ca2+ release pathways are modulated by Ca2+ itself, namely
      Ca(2+)-induced Ca2+ release (classical CICR), and Ca(2+)-sensitized inositol
      1,4,5-trisphosphate (InsP3)-induced Ca2+ release (CSIICR). Both of these pathways
      are thought to be important in generating cytosolic Ca2+ oscillations. Caffeine
      and the sulfhydryl reagent thimerosal (TMS) are frequently used as selective
      modulators of CICR and CSIICR, respectively. We have studied the modes of action
      of caffeine and TMS in sea urchin egg homogenates using the Ca2+ indicator fluo
      3. Cyclic ADP-ribose (cADPR), the only known endogenous compound to cause Ca2+
      release via the ryanodine receptor, was used as an agonist for the classical CICR
      pathway. cADPR and InsP3 each alone caused release of sequestered Ca2+.
      Coaddition of caffeine dose-dependently and dramatically enhanced Ca2+ release
      induced by cADPR. InsP3-induced Ca2+ release was not affected by caffeine, but it
      was amplified by TMS, indicating the existence of the CSIICR pathway in this
      preparation. Surprisingly, cADPR-induced Ca2+ release was also markedly
      potentiated by TMS. TMS alone caused a slow increase in Ca2+ release which was
      not inhibited by heparin and/or procaine, indicating that TMS-induced Ca2+
      release was not due to the actions of endogenous agonists (InsP3 or cADPR) on
      their receptors. All observed actions of TMS were abolished by dithiothreitol. We
      conclude: 1) both the InsP3- and cADPR-controlled Ca2+ release pathways are
      potentiated by TMS, while caffeine is specific for the cADPR pathway, indicating
      that TMS cannot be used as a selective reagent for probing the CSIICR mechanism;
      and 2) the action of TMS on intracellular Ca2+ release is independent of
      endogenous Ca2+ channel agonists, suggesting a novel action of TMS possibly on
      intravesicular Ca2+ handling.

PMID- 8157655
TI  - Purification and characterization of isoquinoline 1-oxidoreductase from
      Pseudomonas diminuta 7, a novel molybdenum-containing hydroxylase.
AB  - Isoquinoline 1-oxidoreductase, which catalyzes the hydroxylation of isoquinoline
      to 1-oxo-1,2-dihydroisoquinoline with concomitant reduction of a suitable
      electron acceptor, was purified from the isoquinoline degrading bacterium
      Pseudomonas diminuta 7 to apparent homogeneity. The native enzyme was a
      heterodimer with a molecular mass of 95 kDa consisting of a 16- and a 80-kDa
      subunit. It contained 0.85 g atom molybdenum, 3.95 g atom iron, 3.9 g atom acid
      labile sulfur, 2.1 mol of phosphate, and 1 mol of CMP/mol of enzyme. CMP and
      phosphate are suggested to originate from molybdopterin cytosine dinucleotide of
      the pterin molybdenum cofactor. It is assumed that the iron and the acid-labile
      sulfur are arranged in two (2Fe-2S) clusters. The isoelectric point of the
      isoquinoline 1-oxidoreductase was within the range of pH 6.2 to 6.8. Cytochrome
      c, ferricyanide, and several non-physiological electron acceptors served as
      oxidizing substrates, whereas O2 and NAD were not used. Isoquinoline 1
      oxidoreductase revealed a high specificity toward the reducing substrates
      isoquinoline, 5-hydroxyisoquinoline, quinazoline, and phthalazine. Isoquinoline 1
      oxidoreductase was inactivated by methanol, arsenite, p-hydroxymercuribenzoate,
      1,10-phenanthroline, and cyanide. Additionally, the enzyme was inactivated upon
      incubation with its substrates isoquinoline, which slowly inhibited the enzyme in
      the absence of an electron acceptor, and 5-hydroxy-isoquinoline, which rapidly
      and very effectively inactivated the enzyme in the presence as well as in the
      absence of the electron acceptors iodonitrotetrazolium chloride, phenazine
      methosulfate, or ferricyanide.

PMID- 8157656
TI  - Tryptophan fluorescence provides a direct probe of nucleotide binding in the
      noncatalytic sites of Escherichia coli F1-ATPase.
AB  - Tryptophan fluorescence was investigated as a tool to study the noncatalytic
      nucleotide-binding sites of Escherichia coli F1-ATPase. Site-directed
      mutagenesis, affinity labeling, and lin-benzo-ATP binding studies had shown that
      residues alpha R365 and beta Y354 are located close to the base moiety of bound
      nucleotide; here, we mutagenized each to tryptophan. The new tryptophans gave a
      fluorescence signal indicating an environment of high (alpha W365) or
      intermediate (beta W354) polarity in unoccupied sites. alpha W365 fluorescence
      was completely quenched by binding of ATP or ADP, providing a direct, specific
      probe of noncatalytic site nucleotide occupancy. Using this signal, we measured
      binding parameters for ATP and ADP, showed that nucleotide binding was magnesium
      dependent, and showed that GTP and ITP did bind to some extent, but AMP, GDP, and
      IDP did not. It was possible to follow initial rates of MgATP hydrolysis and
      noncatalytic site binding under identical conditions; the results indicated that
      occupancy of noncatalytic sites was not required for catalysis. Fluorescence from
      beta W354 was quenched completely by lin-benzo-ATP, but only slightly by ATP or
      ADP. Probably, residue beta 354 is not as closely juxtaposed to the adenine ring
      of bound ATP and ADP as is residue alpha 365. With either alpha W365 or beta W354
      as donor and catalytic site-bound lin-benzo-ADP as acceptor, no fluorescence
      resonance energy transfer was detected, indicating that the distance between non
      catalytic and catalytic sites is > or = 27 A.

PMID- 8157657
TI  - The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of
      high efficiency and specificity.
AB  - Leukotriene-A4 hydrolase (EC 3.3.2.6) cleaved the NH2-terminal amino acid from
      several tripeptides, typified by arginyl-glycyl-aspartic acid, arginyl-glycyl
      glycine, and arginyl-histidyl-phenylalanine, with catalytic efficiencies
      (kcat/Km) > or = 1 x 10(6) M-1 s-1. This exceeds by 10-fold the kcat/Km for its
      lipid substrate leukotriene A4. Catalytic efficiency declined for dipeptides
      which had kcat/Km ratios 10-100-fold lower than tripeptides. Tetrapeptides and
      pentapeptides were even poorer substrates with catalytic efficiencies below 10(3)
      M-1 s-1. The enzyme preferentially hydrolyzed tripeptide substrates and single
      amino acid p-nitroanilides with L-arginine at the NH2 terminus. Peptides with
      proline at the second position were not hydrolyzed, suggesting a requirement for
      an N-hydrogen at the peptide bond cleaved. Peptides with a blocked NH2 terminus
      were not hydrolyzed. The specificity constant (kcat/Km) was optimal at pH 7.2
      with pK values at 6.8 and 7.9; binding was maximal at pH 8.0. Serum albumins
      activated the peptidase, increasing tripeptide affinities (Km) by 3-10-fold and
      specificities (kcat/Km) by 4-13-fold. Two known inhibitors of arginine
      peptidases, arphamenine A and B, inhibited hydrolysis of L-arginine p
      nitroanilide with dissociation constants = 2.0 and 2.5 microM, respectively.
      Although the primary role of LTA4 hydrolase is widely regarded as the conversion
      of the lipid substrate leukotriene A4 into the inflammatory lipid mediator
      leukotriene B4, our data are the first showing that tripeptides are "better"
      substrates. This is compatible with a biological role for the peptidase activity
      of the enzyme and may be relevant to the distribution of the enzyme in organs
      like the ileum, liver, lung, and brain. We present a model which accommodates the
      available data on the interaction of substrates and inhibitors with the enzyme.
      This model can account for overlap in the active site for hydrolysis of
      leukotriene A4 and peptide or p-nitroanilide substrates.

PMID- 8157658
TI  - Dissociation as a result of phosphorylation of an aggregated form of the small
      stress protein, hsp27.
AB  - We have found that the small stress protein, hsp27, exists in extracts of U251 MG
      human glioma cells in two forms: a large or aggregated form (L-hsp27, 300-400
      kDa) and a small or dissociated form (S-hsp27, < 70 kDa), as indicated by
      centrifugation on sucrose density gradients. Dissociation of L-hsp27 to S-hsp27
      was enhanced by incubation of cells with phorbol 12-myristate-13 acetate,
      interleukin-1 alpha, tumor necrosis factor alpha, or okadaic acid, all of which
      are known to enhance or mimic the effects of phosphorylation of hsp27 without
      stimulation of its synthesis. Exposure of cells to chemical stressors, namely,
      NaAsO2 and CdCl2, also enhanced the dissociation of L-hsp27. hsp27 that had been
      labeled with [32P]H3PO4 in U251 MG cells was detected mostly in fractions that
      contained S-hsp27, and the incorporation of radioactivity to S-hsp27 was enhanced
      under conditions that stimulated the dissociation of L-hsp27. L-hsp27 present in
      the (NH4)2SO4 fraction (0-50% saturation) of cell extracts were dissociated to
      32P-labeled hsp27 when incubated in the presence of [gamma-32P]ATP and Mg2+.
      These results indicate that the molecular configuration of hsp27 in cells is
      determined in part by phosphorylation and dephosphorylation of this protein by
      protein kinase(s) and phosphatase(s) and, moreover, that the rapid dissociation
      of the aggregated form of hsp27 by phosphorylation might be involved in a
      cellular defense mechanism for protection against stress.

PMID- 8157659
TI  - Critical nucleotides in the interaction of a LysR-type regulator with its target
      promoter region. catBC promoter activation by CatR.
AB  - We have used site-directed mutagenesis to analyze the importance of nucleotides
      in the catBC promoter region for the binding of CatR, a member of the LysR family
      of DNA-binding proteins and for the in vivo activation of the catBC operon. The
      binding affinity of CatR for its binding site in the catBC promoter region was
      shown to increase about 2.2-fold in the presence of the inducer, cis,cis
      muconate. Nucleotides were targeted for mutagenesis on the basis of previous
      footprinting data and sequence analysis of CatR binding sites. Critical
      nucleotides for CatR binding were found within an imperfect inverted repeat.
      Previous studies have indicated that the LysR family of DNA-binding proteins
      shares a consensus T-N11-A binding motif (Goethals, K., Van Montagu, M., and
      Holsters, M. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1646-1650), but the CatR
      binding site sequence has located within the imperfect inverted repeat a G-N11-A
      instead of the predicted T. Mutagenesis of the G to a T resulted in an increase
      in both the binding of CatR to the catBC promoter and in the in vivo activation.
      Nucleotides within the -35 and -10 regions of the catBC promoter were found to be
      important for promoter activity but not for CatR binding.

PMID- 8157660
TI  - A family of proteins that stabilize the Ran/TC4 GTPase in its GTP-bound
      conformation.
AB  - Ran/TC4, referred to here as Ran1, is a 25-kilodalton nuclear GTP-binding protein
      with an acidic C terminus that lacks any consensus prenylation sites. Here, we
      use a nitrocellulose overlay assay to identify potential effector proteins that
      bind specifically and with high affinity to the GTP-bound form of Ran1. GTP-Ran1
      is shown to bind a variety of proteins, present in many eukaryotic tissues and
      cell extracts. A 28-kDa protein is cytosolic, whereas others, consisting of
      proteins of 86-300 kDa, are primarily localized in the nucleus. Binding is highly
      specific and is not detected by other small GTPases, such as c-Ha-Ras or Rab3A.
      Both deletion of the C-terminal-DEDDDL acidic sequence or alteration of the N
      terminus of Ran1 inhibits binding. However, these altered forms of Ran1 maintain
      the capacity to bind guanyl nucleotides and interact with the nucleotide exchange
      factor. The Ran1-binding proteins potently inhibit release of GTP from Ran1.
      These proteins can therefore maintain Ran1 in the "on" state and are potential
      down-stream effectors for Ran1-dependent cellular processes.

PMID- 8157661
TI  - Interleukin 1 alpha mediates collagenase synthesis stimulated by phorbol 12
      myristate 13-acetate.
AB  - Stimulation of collagenase expression in cultures of normal diploid fibroblasts
      by the tumor promotor phorbol 12-myristate 13-acetate (PMA) occurs secondarily to
      synthesis of unknown intermediary proteins. We have investigated the hypothesis
      that a form of the cytokine interleukin 1 (IL-1) is one intermediate controlling
      PMA-stimulated collagenase expression. Treatment with an IL-1 receptor antagonist
      inhibits the constitutive synthesis of collagenase in early passage fibroblast
      cultures from rabbit. Radioimmunoassay demonstrates that, of the two known IL-1
      forms, IL-1 alpha and IL-1 beta, only IL-1 alpha is synthesized and released into
      the medium of corneal fibroblast cultures. PMA treatment of cells increases the
      level of IL-1 alpha mRNA; this occurs prior to the increase in collagenase mRNA
      and corresponds with increased synthesis and release of IL-1 alpha protein.
      Neutralizing antiserum to IL-1 alpha inhibits constitutive collagenase synthesis.
      Reagents that inhibit the activity of IL-1 alpha (IL-1 receptor antagonist or
      neutralizing antibody) also inhibit the PMA-mediated stimulation of collagenase
      synthesis. These results indicate that constitutive and PMA-stimulated expression
      of collagenase is regulated through an IL-1 alpha intermediate. In vivo,
      regulation of the lytic phase of tissue remodeling through the IL-1 alpha
      intermediate may ensure the recruitment of cells adjacent to the one that
      received the initial stimulus.

PMID- 8157662
TI  - Primary structure analysis and lamin B and DNA binding of human LBR, an integral
      protein of the nuclear envelope inner membrane.
AB  - We have determined the primary structure of human LBR, an integral protein of the
      nuclear envelope inner membrane, and examined its interactions with lamin B and
      DNA. Human LBR is 68% identical to the chicken lamin B receptor and has a basic
      nucleoplasmic amino-terminal domain of 208 amino acids followed by a hydrophobic
      domain with eight putative transmembrane segments. The amino-terminal domain
      contains a Ser-Arg-rich stretch and consensus sites for phosphorylation by
      protein kinase A and p34cdc2 protein kinase. A fusion protein containing the
      amino-terminal domain of human LBR is recognized by autoantibodies from patients
      with primary biliary cirrhosis, and these serum antibodies label the nuclear
      envelope when examined by immunofluorescence microscopy. The LBR amino-terminal
      domain precipitates lamin B from nuclear extracts and retards the migration of
      double-stranded DNA subjected to agarose gel electrophoresis. When immobilized on
      nitrocellulose, the amino-terminal domain of LBR also associates with DNA, and
      the stretch between amino acids 71 and 100, which contains the Ser-Arg-rich
      stretch, is necessary for DNA binding. These results demonstrate that LBR is
      conserved among vertebrate species and that its nucleoplasmic domain can
      potentially mediate the interaction of both the nuclear lamina and the chromatin
      with the inner nuclear membrane.

PMID- 8157663
TI  - Characterization of the human gene encoding LBR, an integral protein of the
      nuclear envelope inner membrane.
AB  - We have characterized the human gene encoding LBR, an integral protein of the
      nuclear envelope inner membrane. Restriction mapping shows that the transcription
      unit spans approximately 35 kilobases. A transcription start site is located
      approximately 4 kilobases 5' to the translation initiation codon, and an RNA
      splice of 3863 bases occurs in the 5'-untranslated region to generate mature HeLa
      cell mRNA. 5' to the identified transcription start site are two CCAAT sequences
      and potential recognition sites for several transcription factors including Sp1,
      AP-1, AP-2, and NF-kB. There are 13 protein coding exons in the LBR gene. LBR's
      nucleoplasmic domain is encoded by exons 1-4, and its hydrophobic domain, with
      eight putative transmembrane segments, is encoded by exons 5-13. The hydrophobic
      domain is homologous to three yeast polypeptides, suggesting that this higher
      eukaryotic gene could have evolved from recombination between a gene that encoded
      a soluble nuclear protein and a membrane protein gene similar to those in yeast.
      These results are the first to demonstrate the structural organization of a
      vertebrate gene encoding an integral membrane protein of the nuclear envelope
      that may be a member of a family of polypeptides conserved in evolution.

PMID- 8157664
TI  - Molecular cloning and biological activity of a novel developmentally regulated
      gene encoding a protein with beta-transducin-like structure.
AB  - In the developing mammalian central nervous system, neural precursor cells show a
      tightly regulated inverse relationship between cell proliferation and
      differentiation. The molecular mechanisms which control the inter-relationship
      between these two events are poorly understood. To approach this problem, we
      previously identified several novel genes which are most prominently expressed in
      the early embryonic brain. Further cloning and sequencing of one such gene,
      Nedd1, revealed that it can encode a protein with a M(r) of 71,000, the amino
      terminal half of which shares significant structural similarity with the beta
      subunit of heterotrimeric GTP-binding proteins. Nedd1 mRNA is strongly expressed
      in early embryonic brain, but it can be detected at low levels in a number of
      adult tissues as well as cell lines and is up-regulated in an embryonal carcinoma
      cell line upon retinoic acid-induced differentiation. Ectopic expression of Nedd1
      gene by means of eukaryotic vectors in various cell lines resulted in varying
      degrees of growth suppression. The strongest effects were evident in
      differentiation-competent neuroblastoma-derived cell lines. Our results suggest
      that the Nedd1 gene may play a role in the differentiation-coupled growth arrest
      in neuronal cells.

PMID- 8157665
TI  - Free cholesterol loading of macrophages stimulates phosphatidylcholine
      biosynthesis and up-regulation of CTP: phosphocholine cytidylyltransferase.
AB  - Atheroma macrophages accumulate large amounts of free cholesterol (FC) as well as
      cholesteryl ester (CE). An important adaptive response to FC loading might be
      increased cellular phospholipid to accommodate the excess FC. To explore this
      idea, J774 macrophages were incubated for 48 h without lipid, with acetyl-low
      density lipoprotein to induce mostly CE loading, or with acetyl-low density
      lipoprotein plus an acyl-CoA:cholesterol O-acyltransferase inhibitor (58035) to
      induce marked FC loading. The total phospholipid content approximately doubled in
      FC-loaded versus control or CE-loaded macrophages, with phosphatidylcholine
      showing the largest increase (approximately 2.5-fold versus control). Electron
      micrographs revealed the presence of multiple intracellular membrane whorls in
      the FC-loaded macrophages but not in the control or CE-loaded macrophages.
      [3H]Choline incorporation into phosphatidylcholine was also greater in FC-loaded
      macrophages versus control or CE-loaded macrophages, whereas
      [3H]phosphatidylcholine degradation was similar in all of the macrophages. In
      these experiments and in others that used non-lipoprotein cholesterol, there was
      a very close correlation between cellular FC content and phosphatidylcholine
      biosynthesis. To determine the mechanism of increased phosphatidylcholine
      synthesis, FC-loaded and CE-loaded macrophages were pulsed with [3H]choline, then
      chased and assayed for labeled phosphatidylcholine biosynthetic precursors. The
      only major differences were a 2-fold greater disappearance of label from
      [3H]choline phosphate and a 5-fold greater appearance of label in CDP-[3H]choline
      in the FC-loaded macrophages. These data suggest a stimulation of
      CTP:phosphocholine cytidylyltransferase (CT), which was confirmed by microsomal
      CT assays. Further studies revealed that the increase in phosphatidylcholine
      biosynthesis in FC-loaded macrophages was: (a) reversible under conditions of
      high density lipoprotein3-mediated cellular cholesterol efflux; (b) not blocked
      by cycloheximide-induced protein synthesis inhibition; and (c) not associated
      with increased CT mRNA levels. Thus, FC loading of macrophages leads to an
      increase in phosphatidylcholine mass which is caused by increased
      phosphatidylcholine biosynthesis. The mechanism appears to be FC-mediated post
      translational activation of CT. This adaptive response may be important for
      atheroma macrophage survival, and disruption of the response may lead to
      macrophage necrosis and lesion progression.

PMID- 8157667
TI  - A hammerhead ribozyme inhibits the proliferation of an RNA coliphage SP in
      Escherichia coli.
AB  - Ribozymes are potentially powerful tools for the suppression of intracellular
      gene expression. However, the few reports that exist of their activities in
      bacteria have described mixed success. Chuat and Galibert (Chuat, J.-C., and
      Galibert, F. (1989) Biochem. Biophys. Res. Commun. 162, 1025-1029) failed to
      detect any trans-activities of hammerhead ribozymes in Escherichia coli, while
      Sioud and Drlica (Sioud, M., and Drlica, K. (1991) Proc. Natl. Acad. Sci. U.S.A.
      88, 7303-7307) reported complete inhibition of expression of the gene for a
      nonbacterial protein, HIV-1 integrase, by trans-acting hammerhead ribozymes in E.
      coli. It is of interest to determine whether ribozymes can really be used in
      natural bacterial systems (Altman, S. (1993) Proc. Natl. Acad. Sci. U.S.A. 90,
      10898-10900). We now report that a ribozyme designed to cleave the A2 gene of RNA
      coliphage SP, when transcribed from a plasmid in E. coli caused failure of the
      proliferation of progeny phage. Inactive ribozymes with altered catalytic
      sequences did not affect phage growth. These results indicate that it is mainly
      the catalytic activity of the ribozyme and not its function as an antisense
      molecule that is responsible for suppressing the proliferation of the RNA phage.
      Moreover, an analysis based on numbers of plaque-forming units and the function
      of the A2 protein indicated that antisense RNA may successfully compete with
      ribosomes in targeting mRNA while ribozymes in this study may not compete with
      ribosomes in naturally occurring bacterial transcription/translation-coupled
      systems.

PMID- 8157666
TI  - Reconstitution of recombinant 33-kDa subunit of the clathrin-coated vesicle H(+)
      ATPase.
AB  - Evidence suggests that the ATP hydrolytic sector of the clathrin-coated vesicle
      proton-translocating ATPase is composed of four subunits of molecular masses of
      70, 58, 40, and 33 kDa (Xie, X. S., and Stone, D. K. (1988) J. Biol. Chem. 263,
      9859-9867). We have now expressed recombinant 33-kDa polypeptide in Escherichia
      coli and in Spodoptera frugiperda (Sf9) cells. This subunit, renatured and
      purified from both sources, lacks intrinsic ATPase activity. Co-reconstitution of
      these recombinant 33-kDa polypeptides and recombinant 40-kDa subunit to a
      biochemically prepared 70-58-kDa subcomplex results in a 6-fold stimulation of
      calcium-activated, N-ethyl-maleimide-sensitive ATPase activity, documenting the
      essential role of the 33- and 40-kDa components in vacuolar type proton pump
      function and furthering the aim of reconstitution of a purely recombinant
      hydrolytic core.

PMID- 8157668
TI  - The covalent eukaryotic topoisomerase I-DNA intermediate catalyzes pH-dependent
      hydrolysis and alcoholysis.
AB  - Eukaryotic topoisomerase I catalysis was characterized by the use of a DNA
      substrate system, which allows uncoupling of cleavage and ligation half
      reactions. Covalent topoisomerase I-DNA intermediates formed by cleavage without
      concomitant ligation were able to catalyze hydrolysis of the 3'-phosphotyrosyl
      bond in the pH range 7.5-10, with a broad pH optimum between pH 8.5 and 9.5. In
      comparison, the DNA cleavage and ligation activity of topoisomerase I were found
      to be independent of pH in the pH range 7-10 and strongly impaired at higher pH
      values. Moreover, different polyhydric alcohol compounds were found to function
      as nucleophiles at pH 9 to facilitate the release of topoisomerase I. The
      hydrolysis and alcoholysis activities of topoisomerase I were specific for the 3'
      phosphotyrosyl bond and blocked by enzyme denaturation or proteolysis. Taken
      together the data suggest that site-specific hydrolysis or alcoholysis mediated
      by topoisomerase I-DNA complexes reflects the ability of the enzyme to direct the
      activation of the 3'-phosphotyrosyl bond or the incoming nucleophile. Analysis of
      enzyme-directed coupling of non-DNA nucleophiles to the cleaved DNA strand may
      provide a useful tool for elucidation of the biochemical mechanism of type I DNA
      topoisomerases.

PMID- 8157669
TI  - Characterization of a stable form of human meizothrombin derived from recombinant
      prothrombin (R155A, R271A, and R284A).
AB  - Meizothrombin is a transient intermediate produced during the activation of
      prothrombin by the prothrombinase complex. Because meizothrombin is very
      sensitive to further activation and autolysis, its isolation is possible only in
      the presence of active site thrombin inhibitors. This complicates studies of the
      activities and functions of meizothrombin. As a model, we have expressed a mutant
      human prothrombin cDNA (R155A, R271A, R284A) with three of the cleavage sites
      modified so that they are no longer cleaved by factor Xa or thrombin. Several
      stable baby hamster kidney cell lines were isolated that secreted up to 20
      micrograms/ml of carboxylated mutant prothrombin. After purification, the mutant
      prothrombin was activated by the prothrombinase complex or by ecarin, resulting
      in the formation of a meizothrombin-like molecule. Electrophoretic analysis and
      NH2-terminal sequence analysis were consistent with cleavage of a single bond
      between Arg320-Ile321 and proper processing of the prepropeptide. The
      meizothrombin was stable for weeks at 4 degrees C. Activation in the presence of
      dansylarginine N-(3-ethyl-1,5-pentanediyl) amide confirmed the conversion of
      prothrombin via meizothrombin. Compared with human plasma-derived thrombin,
      recombinant meizothrombin demonstrated approximately 7% clotting activity, 100% p
      toluene-sulfonylarginine methyl ester esterase activity, and approximately 35%
      S2238 amidolytic activity, and could attenuate fibrinolysis.

PMID- 8157670
TI  - Characterization of type I procollagen N-proteinase from fetal bovine tendon and
      skin. Purification of the 500-kilodalton form of the enzyme from bovine tendon.
AB  - Procollagen N-proteinase (EC 3.4.24.14) is the enzyme that specifically cleaves
      the NH2-terminal propeptides from type I procollagen. Two forms of N-proteinase
      with apparent molecular sizes of 300 and 500 kDa were found in partially purified
      preparations from fetal bovine tendon extracts. The 500-kDa form of enzyme was
      purified 16,000-fold with a recovery of 8% from the extracts of the tendons by
      six purification steps. The purified enzyme was a neutral, Ca(2+)-dependent
      proteinase (5-10 mM) that was inhibited by metal chelators. The 500-kDa enzyme
      contained unreduced polypeptides of 58, 125, 170, and 190 kDa which were
      separated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate.
      Electron microscopic study indicated that the enzyme molecules were generally
      globular and had diameters of 33 +/- 4 nm. Other properties of the 500-kDa enzyme
      were: 1) the Km for type I procollagen is 35 nM at pH 7.5 and 35 degrees C, and
      the kcat is 290 h-1; 2) the activation energy for reaction with type I
      procollagen is 10,050 cal mol-1; 3) the isoelectric point is 3.8; 4) the enzyme
      cleaves the NH2-terminal propeptides of type II procollagen as well as type I
      procollagen but not of type III procollagen; and 5) the enzyme specifically
      cleaves a -Pro-Gln- bond in the pro-alpha 1(I) chain and an -Ala-Gln- bond in the
      pro-alpha 2(I) chain. The bovine N-proteinase with a mass of 300 kDa was found to
      be similar to the 500-kDa enzyme and appeared to be a degraded form of the 500
      kDa enzyme generated during purification. The N-proteinase from fetal bovine skin
      extracts also contained 300-kDa and 500-kDa enzyme forms.

PMID- 8157671
TI  - The di- and tripeptide transport protein of Lactococcus lactis. A new type of
      bacterial peptide transporter.
AB  - Lactococcus lactis takes up di- and tripeptides via a proton motive force
      dependent carrier protein. The gene (dtpT) encoding the di-tripeptide transport
      protein of L. lactis was cloned by complementation of a dipeptide transport
      deficient and proline auxotrophic Escherichia coli strain. Functional expression
      of the dipeptide transport gene was demonstrated by uptake studies of alanyl
      [14C]glutamate and other peptides in E. coli cells. The di-tripeptide transport
      protein catalyzes proton motive force-driven peptide uptake and dipeptide
      exchange activity. The nucleotide sequence of dtpT was determined and the
      translated sequence corresponds with a protein of 463 amino acid residues.
      Hydropathy profiling indicates that the protein could form 12 membrane-spanning
      segments with the amino and carboxyl termini at the outer surface of the
      membrane. A secondary structure model is presented which is substantiated by
      analysis of DtpT-PhoA fusion constructs. Amino acid sequence comparisons showed
      no significant homology with other bacterial peptide transport systems nor with
      any other known protein. Flanking regions of the di-tripeptide transport gene
      were used to delete dtpT from the chromosome of L. lactis. Genetic and
      biochemical characterization of this mutant indicates that DtpT is the only
      transport protein in L. lactis for hydrophilic di- and tripeptides.

PMID- 8157672
TI  - A partial structural repeat forms the heterodimer self-association site of all
      beta-spectrins.
AB  - The self-polymerization of alpha beta-spectrin heterodimers to form tetramers and
      higher oligomers is central to its role as a membrane stabilizer and organizer.
      Mutations near the amino terminus of alpha I sigma 1-spectrin or the COOH
      terminus of beta I sigma 1-spectrin often lead to profound impairment heterodimer
      polymerization and to hemolytic disease of varying severity. Previous studies
      using an 80-kDa univalent fragment of alpha I sigma 1-spectrin have established
      that the amino-terminal segment of alpha I sigma 1-spectrin mediates the
      association of the alpha subunit with either intact heterodimers or with isolated
      beta-spectrin (beta I sigma 1). However, the nature of the self-association site
      in beta-spectrin has remained unclear. In the present study, native beta-spectrin
      and recombinant beta-spectrin peptides representing COOH-terminal portions of two
      alternative transcripts of the gene on chromosome 2 (beta I sigma 1 or
      "erythrocyte" spectrin and beta I sigma 2 or "muscle" spectrin), and one
      transcript of the gene on chromosome 14 (beta II sigma 1 or "beta G-fodrin") have
      been examined for their ability to bind either intact alpha beta-spectrin or the
      alpha I-spectrin 80-kDa univalent fragment. Deletion of the nonhomologous beta
      spectrin sequence downstream of repeat 17 (spectrin domain III) had no
      discernible effect on binding. Truncations proximal to codon 2085 of beta I sigma
      1-spectrin demonstrated a precipitous loss of activity, accounted for by a loss
      of both binding affinity and capacity. Further truncations to repeat 16 (codon
      1979) restored binding activity to levels approximating that of the intact
      molecule. Repeat 16/17 and 17/16 chimeras displayed reduced binding activity.
      Collectively, these data indicate that the beta-subunit self-association site is
      highly sensitive to conformation, involves widespread interactions within the
      17th repeat unit, is largely independent of sequences in domain III, and can be
      recreated by the deletion of all residues distal to the COOH end (codon 1979) of
      the 16th and presumably other spectrin sequence repeat units. All beta-spectrins
      appear to use this binding motif, regardless of the nature of the nonhomologous
      sequence in domain III.

PMID- 8157673
TI  - Alteration of lipid profiles in plasma of transgenic mice expressing human
      lipoprotein lipase.
AB  - Lipoprotein lipase (LPL) is a key enzyme required for the hydrolysis of
      triglyceride-rich particles. To assess the effects of increased plasma LPL on
      lipoprotein levels, transgenic mice expressing human LPL (hLPL) were produced.
      Abundant hLPL transcripts were detected in RNA from different tissues of
      transgenic mice which resulted in an increase in post-heparin plasma LPL activity
      of approximately 154%. On rodent chow (p = 0.01) and after a 16-h fast (p =
      0.001), plasma triglycerides in transgenic mice were decreased by approximately
      50% as compared to littermate controls. Gel filtration chromatography showed a 2
      3-fold decrease in very low density lipoprotein triglycerides and cholesterol
      enrichment of low density lipoprotein. Transgenic mice maintained on a high
      carbohydrate diet exhibited a 78% (p = 0.03) lowering of low density lipoprotein
      and very low density lipoprotein cholesterol levels, in addition to a 68% (p =
      0.01) lowering of total to high density lipoprotein cholesterol (TC/HDL-C) ratios
      compared to controls. The distribution of apoA-I and A-II were similar in the
      transgenics and their non-transgenic littermates, while the apoE distribution was
      mildly altered in the plasma from the transgenic mice. These data demonstrate
      that moderate increases in total LPL activity are associated with significant
      changes in lipoprotein levels and altered composition of lipoprotein particles.

PMID- 8157674
TI  - Biochemical characterization of valosin-containing protein, a protein tyrosine
      kinase substrate in hematopoietic cells.
AB  - Engagement of the T cell antigen receptor (TCR) leads to activation of multiple
      tyrosine kinases and rapid tyrosine phosphorylation of intracellular protein
      substrates. A number of these substrates have been identified and they include
      TCR subunits, phospholipase C-gamma 1, p95vav, and ezrin. In a recent study we
      have demonstrated that VCP (valosin-containing protein) becomes tyrosine
      phosphorylated upon TCR cross-linking. Analysis of the predicted amino acid
      sequence of this protein indicates that it is a member of a family of oligomeric
      proteins containing duplicated domains with predicted ATPase activity. In the
      current study we determine the site of tyrosine phosphorylation in VCP,
      demonstrate that murine VCP indeed is an oligomeric ATPase, and show that the
      tyrosine phosphorylation of the protein has no effect on VCP ATPase activity.
      Recent evidence suggests that VCP associates with clathrin. A possible role of
      tyrosine phosphorylation in regulating this protein-protein interaction is
      discussed.

PMID- 8157675
TI  - Signal transduction by a chimeric insulin-like growth factor-1 (IGF-1) receptor
      having the carboxyl-terminal domain of the insulin receptor.
AB  - Insulin-like growth factor-1 receptors (IGF-1R) and insulin receptors (IR) are
      closely related tyrosine kinases. However, the IR plays a major role in
      metabolism control, whereas the IGF-1R is mainly involved in growth and
      differentiation. With these observations in mind, we wished to define the regions
      of IR and IGF-1R responsible for generation of biological specificity. We
      constructed a chimeric IGF-1R in which the carboxyl-terminal domain was replaced
      by that of IR. This receptor (IGF/CTIR) was expressed in NIH3T3 cells, and we
      compared its biological activity with that of wild-type receptors. The IGF/CTIR
      was fully functional regarding kinase activity and biological properties.
      Comparison of insulin and IGF-1 effects on IR and IGF-1R cells, respectively,
      indicated that the IR is more efficient in stimulating glycogen synthesis and
      p44mapk activity than is the IGF-1R. Interestingly, in IGF/CTIR16 cells
      expressing only 250,000 receptors glycogen synthesis was better stimulated than
      in IGF-1R cells with 600,000 receptors. Similarly, p44mapk activation was
      slightly higher in IGF/CTIR16 cells than in IGF-1R cells. These results suggest
      that the carboxyl-terminal domain of IR is more tightly coupled to the
      stimulation of glycogen synthesis and to the p44mapk pathway than is that of IGF
      1R. We propose that this domain plays a crucial role in the transmission of
      biological effects and could account, at least in part, for receptor specificity.

PMID- 8157676
TI  - Disulfide mutants of the binding domain of the rat low affinity nerve growth
      factor receptor (p75NGFR).
AB  - The binding domain of the low affinity nerve growth factor receptor (p75NGFR) is
      built from four "cysteine repeats," with almost identical patterns of half
      cystine residues. To study the pattern of disulfide bridging within each cysteine
      repeat, we have mutated pairs of cysteine residues, primarily in the fourth
      repeat, and have tested the relative ability of each mutant to be cross-linked to
      the nerve growth factor after transient expression in COS 7 cells. The results
      give an indication of the relative importance of different disulfide bonds for
      the stability of the active conformation. Immunofluorescent staining shows that
      all of these proteins, even those that may be partially misfolded, are expressed
      to varying degrees on the surface of COS cells. They can also be detected by the
      monoclonal antibody MC192 on a Western blot following electrophoresis on a
      nondenaturing gel. Some cannot, however, be detected by MC192 on a Western blot
      after heat denaturation in SDS. The ability to refold under these conditions
      correlates in general with the ability of the mutant protein to bind nerve growth
      factor on the surface of COS cells.

PMID- 8157677
TI  - Stimulation of calcification of growth plate cartilage matrix vesicles by binding
      to type II and X collagens.
AB  - Matrix vesicles (MV), microstructures which rapidly accumulate Ca2+ and induce
      mineral formation in vitro, are linked to type II and X collagens and
      proteoglycans in the hypertrophic cartilage. However, the roles of these matrix
      proteins on MV function are not known. This led us to investigate the influence
      of type II and X collagen binding on Ca2+ uptake by MV. MV isolated from chicken
      growth plate cartilage were treated with pure bacterial collagenase and 1 M NaCl
      in synthetic cartilage lymph to selectively and completely remove associated type
      II and X collagens. Uptake of 45Ca2+ by these collagen-depleted vesicles was
      markedly reduced. Further treatment with detergent, which disrupted the membrane,
      restored Ca2+ uptake, indicating that the vesicle membrane structure and the
      nucleational core inside the vesicle lumen were still intact after the
      collagenase and 1 M NaCl treatments. Readdition of either native type II or X
      collagen to the collagenase, 1 M NaCl-treated MV stimulated their Ca2+ uptake to
      levels similar to those of untreated vesicles. Pepsin-treated type II and X
      collagens were less effective in stimulating Ca2+ uptake, indicating that non
      triple helical domains of these collagens were involved. The pepsin treatment of
      these collagens also decreased their binding to annexin V (anchorin CII), one of
      three annexins found in MV, suggesting that annexin V is involved in mediating
      the binding of type II and X collagens to the MV surface. Furthermore, treatment
      of collagenase, 1 M NaCl-treated MV with chymotrypsin, which damaged annexin V as
      well as many other MV proteins, prevented the stimulation of Ca2+ uptake by these
      collagens. Thus, the interaction between type II and X collagens with MV
      activates the influx of Ca2+ into MV and may play an important role in
      calcification of the vesicles.

PMID- 8157678
TI  - Yolk protein factor 1 is a Drosophila homolog of Ku, the DNA-binding subunit of a
      DNA-dependent protein kinase from humans.
AB  - Yolk protein factor 1 (YPF1) is a heterodimeric DNA-binding protein from
      Drosophila melanogaster. In this report, we describe evidence that YPF1 is a
      homolog of Ku, a human autoimmune antigen that is the DNA-binding subunit of a
      DNA-dependent protein kinase. In vitro this kinase phosphorylates several
      transcription factors and, at the time of transcription initiation, the carboxyl
      terminal domain of RNA polymerase II. We find that a cDNA clone for the smaller
      subunit (beta) of YPF1 encodes a 72-kDa protein that has extensive homology to
      the smaller subunit of the heterodimeric Ku protein (24% identity, 51% similarity
      over the entire 631 amino acid length). Further, the larger YPF1 subunit (alpha)
      shares immunological epitopes with the larger subunit of Ku. YPF1 and Ku also
      appear to bind DNA similarly. Southwestern blot experiments demonstrate that,
      like the Ku protein, the smaller YPF1 subunit binds DNA in the absence of the
      larger subunit. Further, cross-linking experiments indicate that, once again like
      the Ku protein, both subunits make contact with DNA when YPF1 binds as a
      heterodimer. YPF1 beta transcripts occur at low levels in all stages of
      Drosophila development except during oogenesis and early embryogenesis when they
      increase 25-fold. In situ hybridization localizes the beta gene to position 34C
      on the left arm of chromosome 2.

PMID- 8157679
TI  - Xylosyl transfer to an endogenous renal acceptor. Characteristics of the reaction
      and properties of the product.
AB  - In the course of a study of UDP-xylose:proteoglycan core protein
      xylosyltransferase (EC 2.4.2.26), another xylosyltransferase was discovered in
      the soluble fraction of a rat kidney homogenate. The latter enzyme catalyzed
      [3H]xylosyl transfer from UDP-[3H]xylose to an endogenous acceptor and yielded a
      product in which the xylose was bound by an alkali-stable linkage. It was
      therefore concluded that the acceptor was not the core protein of one of the
      proteoglycans containing a xylose-->serine linkage, since this linkage is cleaved
      by alkali. The [3H]xylose-labeled product emerged with the void volume when
      chromatographed on Sephadex G-50, it was precipitated by trichloroacetic acid,
      and it had a mobility on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis corresponding to a molecular mass of about 32,000 Da. Digestion
      with trypsin or alpha-amylase degraded the labeled product to small fragments, as
      determined by gel chromatography, suggesting that it was a glycoprotein related
      to glycogen. A product of similar characteristics was formed when UDP-[3H]glucose
      was substituted for UDP-[3H]xylose as the glycosyl donor, and the two nucleotide
      sugars were mutually competitive in the respective transfer reactions, indicating
      that they were substrates for the same enzyme. On the basis of these findings, it
      was tentatively concluded that the xylosyltransferase and its acceptor were the
      renal form of glycogenin.

PMID- 8157680
TI  - Xylosyl transfer to an endogenous renal acceptor. Purification of the transferase
      and the acceptor and their identification as glycogenin.
AB  - A xylosyltransferase in rat kidney, tentatively identified as glycogenin (Meezan,
      E., Ananth, S., Manzella, S., Campbell, P., Siegal, S., Pillion, D. J., and
      Roden, L. (1994) J. Biol. Chem. 269, 11503-11508), was purified by a procedure in
      which affinity chromatography on UDP-glucuronic acid-agarose was a particularly
      useful step. The purified material was nearly homogeneous, as shown by SDS
      polyacrylamide gel electrophoresis and silver staining, and had an
      electrophoretic mobility corresponding to a M(r) of 32,000. The purified enzyme
      possessed both glucosyl- and xylosyltransferase activity, and incubation with UDP
      [3H]xylose or UDP-[3H]glucose yielded a single macromolecular product, which had
      the same electrophoretic mobility as the major silver-stained component. These
      results indicate that the kidney transferase was indeed glycogenin and that it
      was functionally analogous to the larger glycogenin species previously isolated
      from rabbit muscle. Further examination of the properties of the rat kidney
      enzyme showed, i.a., that it was inhibited strongly by cytidine 5'-diphosphate.
      This effect was used to advantage in an alternative purification procedure, which
      was applied to beef kidney and involved adsorption of the enzyme to UDP
      glucuronic acid-agarose and subsequent elution with cytidine 5'-diphosphate. In
      contrast to glycogenin, glycogen synthase did not catalyze transfer from UDP
      xylose, and it is suggested that the incorporation of xylose into glycogen
      observed by other investigators was due to glycogenin-catalyzed xylosyl transfer
      and subsequent chain elongation by glycogen synthase.

PMID- 8157681
TI  - Analysis of androgen receptor-DNA interactions with receptor proteins produced in
      insect cells.
AB  - Wild-type rat androgen receptor and four of its deletion mutants were produced in
      insect cells using the baculovirus expression system. Inclusion of androgen, but
      not estrogen, progesterone, or glucocorticoid, in culture medium increased the
      yield of soluble androgen receptors, although the majority of receptors still
      remained in the insoluble form (Xie, Y.-B., Sui, Y.-P., Shan, L.-X., Palvimo, J.
      J., Phillips, D. M., and Janne, O. A. (1992) J. Biol. Chem. 267, 4939-4948). The
      wild-type receptor interacted with an androgen response element (ARE) with a 2-6
      fold higher affinity (KD = 0.5 nM) than mutants with deletions outside the DNA
      binding domain (delta 40-147, delta 38-296, delta 46-408, and delta 788-902
      mutants), suggesting that sequences flanking the DNA-binding region influence the
      stability of receptor-DNA complexes. Changes in spacing (n = 3) between the two
      ARE half-sites by a single nucleotide (n - 1, n + 1) or by 10 bases (n + 10)
      abolished the full-length receptor's ability to form stable complexes with DNA.
      Binding to AREs with altered spacing could not be restored by antisera against
      the N-terminal domain of the receptor that stabilize androgen receptor-DNA
      interactions with many naturally occurring strong and weak AREs. Methylation
      interference and 1,10-phenanthroline copper footprinting analyses revealed that
      the receptor binds to DNA as a dimer. Dimer formation was demonstrated directly
      by mixing full-length and delta 46-408 mutant receptors, which resulted in the
      formation of heterodimeric receptor-DNA complexes. The half-time of dissociation
      of the wild-type receptor from a consensus ARE sequence was about 3 min at 22
      degrees C. Collectively, androgen receptor binds to DNA with properties similar
      to, but not identical with, those of glucocorticoid receptor, indicating that
      regions outside the DNA-binding domain are important to ensure androgen
      specificity of transcriptional regulation.

PMID- 8157682
TI  - GLUT-2 gene transfer into insulinoma cells confers both low and high affinity
      glucose-stimulated insulin release. Relationship to glucokinase activity.
AB  - The rat insulinoma cell line RIN 1046-38 loses glucose-stimulated insulin
      secretion as a function of time in culture. We found that the loss of glucose
      sensing in these cells was correlated with the loss of expression of GLUT-2 and
      glucokinase. Stable transfection of RIN cells with a plasmid containing the GLUT
      2 cDNA conferred glucose-stimulated insulin release in intermediate but not high
      passage cells, with the near-maximal 3-fold increase occurring at 50 microM
      glucose. GLUT-2 expressing cells also exhibited a larger response to the
      combination of 5 mM glucose + 1 microM forskolin than untransfected cells (7.9
      versus 1.6-2.7-fold, respectively). GLUT-2 expressing intermediate passage, but
      not high passage, RIN cells exhibited a 4-fold increase in glucokinase enzymatic
      activity relative to nonexpressing controls. Glucokinase activity was also
      increased by transfer of the GLUT-2 gene into intermediate passage RIN cells via
      recombinant adenovirus. Preincubation of GLUT-2 expressing intermediate passage
      RIN cells with 2-deoxyglucose to inhibit low Km hexokinases resulted in a glucose
      stimulated insulin secretion response that was shifted toward the physiologic
      range. These studies indicate that GLUT-2 expression confers both a high and low
      affinity glucose-stimulated insulin secretion response to intermediate passage
      RIN cells.

PMID- 8157683
TI  - Human cathepsin S: chromosomal localization, gene structure, and tissue
      distribution.
AB  - The human lysosomal cysteine proteinases, cathepsins H, L, and B, have been
      mapped to chromosomes 15, 9, and 8, respectively, and the genomic structures of
      cathepsins L and B have been determined. We report here the chromosomal
      localization and partial gene structure for a recently sequenced human cysteine
      proteinase, cathepsin S. A 20-kilobase pair genomic clone of the human cathepsin
      S gene was isolated from a human fibroblast genomic library and used to map the
      human cathepsin S gene to chromosome 1q21 by fluorescence in situ hybridization.
      This clone contains exons 1 through 5, introns 1 through 4, part of intron 5, and
      > 7 kilobase pairs of the 5'-flanking sequence. The gene structure of human
      cathepsin S is similar to that of cathepsin L through the first 5 exons, except
      that cathepsin S introns are substantially larger. Sequencing of the 5'-flanking
      region revealed, similar to human cathepsin B, no classical TATA or CAAT box. In
      contrast to cathepsin B, cathepsin S contains only two SP1 and at least 18 AP1
      binding sites that potentially could be involved in regulation of the gene. This
      5'-flanking region also contains CA microsatellites. The presence of AP1 sites
      and CA microsatellites suggest that cathepsin S can be specifically regulated.
      Results of Northern blotting using probes for human cathepsins B, L, and S are
      consistent with this hypothesis; only cathepsin S shows a restricted tissue
      distribution, with highest levels in spleen, heart, and lung. In addition,
      immunostaining of lung tissue demonstrated detectable cathepsin S only in lung
      macrophages. The high level of expression in the spleen and in phagocytes
      suggests that cathepsin S may have a specific function in immunity, perhaps
      related to antigen processing.

PMID- 8157684
TI  - Functional role of a cytoplasmic aromatic amino acid in muscarinic receptor
      mediated activation of phospholipase C.
AB  - The N-terminal portion of the third intracellular loop (i3) of muscarinic
      acetylcholine and other G protein-coupled receptors has been shown to largely
      determine the G protein coupling profile of a given receptor subtype. Using the
      rat m3 muscarinic receptor as a model system, we have recently demonstrated that
      a tyrosine residue (Tyr-254), located at the beginning of the i3 domain, is
      critically involved in muscarinic receptor-mediated stimulation of
      phosphatidylinositol (PI) hydrolysis (Bluml, K., Mutschler, E., and Wess, J.
      (1994) J. Biol. Chem. 269, 402-405). This study was designed to investigate the
      functional role of this amino acid in further molecular detail. Replacement of
      Tyr-254 (rat m3 receptor) with alanine or exchange of its position with Ile-253
      virtually abolished receptor-mediated stimulation of PI hydrolysis studied in
      transfected COS-7 cells. In contrast, substitution of Tyr-254 by other aromatic
      residues such as phenylalanine or tryptophan resulted in mutant receptors that
      behaved functionally similar to the wild type m3 receptor. Introduction of Tyr
      254 into the corresponding position (Ser-210) of the m2 muscarinic receptor
      (which is only poorly coupled to PI turnover) did not result in an enhanced PI
      response. However, "reinsertion" of Tyr-254 into a functionally inactive chimeric
      m3/m2 muscarinic receptor (containing m2 receptor sequence at the N terminus of
      the i3 loop) yielded a mutant receptor that was able to stimulate PI hydrolysis
      to a similar maximum extent as the wild type m3 receptor. Taken together, our
      data provide strong evidence that muscarinic receptor-mediated stimulation of PI
      metabolism is critically dependent on the presence and proper positioning of an
      aromatic residue at the beginning of the i3 loop.

PMID- 8157685
TI  - Incorporation of adenovirus into a ligand-based DNA carrier system results in
      retention of original receptor specificity and enhances targeted gene expression.
AB  - Adenovirus type 5 was modified by coupling an asialoglycoprotein-polylysine
      conjugate to the virus by reactions that activate carbohydrate residues. Wild
      type virus modified in this manner had greatly decreased infectivity toward
      normally susceptible HeLa S3 (asialoglycoprotein receptor (-)) and SK Hep1
      (asialoglycoprotein receptor (-)) cells leaving 91 and 86% viable, respectively,
      after 48 h. However, with Huh 7 (asialoglycoprotein receptor (+)) cells, modified
      virus retained its infectivity leaving only 19% of cells viable under identical
      conditions. Modified virus was complexed to DNA in the form of a plasmid, pSVHBV
      surf, containing the gene for hepatitis B surface antigen as a marker of gene
      expression. Huh 7, receptor (+), cells treated with modified wild type, and
      modified replication-defective d1312 virus complexed to DNA raised antigen levels
      by approximately 13- and 30-fold, respectively, compared with asialoglycoprotein
      polylysine DNA complex alone. Competition with a large excess of an
      asialoglycoprotein blocked the enhancement by more than 95%. Using a beta
      galactosidase marker gene, the number of cells transfected by modified virus was
      found to be 200-fold higher than complex alone. Yet, specificity was retained
      exclusively for asialoglycoprotein receptor-bearing cells. These data indicate
      that adenovirus can be chemically modified by coupling ligands resulting in
      targeted gene expression dictated specifically by receptor recognition of the
      attached ligand.

PMID- 8157686
TI  - Type I phosphatidylinositol 4-phosphate 5-kinase isoforms are specifically
      stimulated by phosphatidic acid.
AB  - A phosphatidylinositol 4-phosphate (PIP) kinase was isolated and purified to near
      homogeneity from bovine erythrocyte membranes. The PIP kinase was extracted from
      bovine erythrocyte membranes with a high salt wash, followed by phosphocellulose
      and phenyl-Sepharose chromatography. The predominant protein after phenyl
      Sepharose purification had a molecular size of 68 kDa. Renaturation of PIP kinase
      activity after SDS-PAGE showed that a 68-kDa protein was able to phosphorylate
      PIP. An antibody developed against the 68-kDa protein Western blots the 68-kDa
      protein and is able to immunoprecipitate the 68-kDa protein and PIP kinase
      activity from membrane extracts. Based on functional studies, the 68-kDa protein
      is indistinguishable from the type I PIP kinase previously characterized from
      human erythrocyte membranes (Bazenet, C. E., Ruano, A.R., Brockman, J.L., and
      Anderson, R.A. (1990) J. Biol. Chem. 265, 18012-18022). These studies also show
      that the type I PIP kinases, but not the type II PIP kinase, are stimulated by
      phosphatidic acid, suggesting alternative roles for these enzymes. Two
      immunoreactive isoforms of the type I PIP kinase, of 68 and 90 kDa, were
      identified in rat brain and partially purified. Both of these isoforms are also
      stimulated by phosphatidic acid.

PMID- 8157687
TI  - Differential recognition by conglutinin and mannan-binding protein of N-glycans
      presented on neoglycolipids and glycoproteins with special reference to
      complement glycoprotein C3 and ribonuclease B.
AB  - Conglutinin and mannan-binding protein are serum proteins that have similar
      carbohydrate binding specificities toward high mannose-type oligosaccharides, and
      yet only conglutinin binds the complement glycoprotein iC3b, which contains
      oligosaccharides of this type. In the present study, the interactions of
      conglutinin and mannan-binding protein were evaluated with the complement
      glycoprotein C3, including various physiologically derived fragments of this
      glycoprotein, and neoglycolipids prepared from oligosaccharides released from C3
      and its isolated alpha and beta chains. Several conclusions can be drawn. First,
      the interaction of conglutinin is profoundly influenced by the state of the
      protein moiety of the alpha chain in the vicinity of the glycosylation site Asn
      917. Second, the binding to the C3-derived glycoprotein iC3b appears to be
      exclusively mediated through the Man8 or Man9 oligosaccharide on the alpha chain;
      there is no evidence for other N-linked oligosaccharides on C3 that are uniquely
      bound by conglutinin. Third, although conglutinin shows a more restricted binding
      relative to mannan-binding protein toward the oligosaccharides free of protein,
      it has a broader binding pattern toward the oligosaccharides as presented on C3
      derived glycoproteins. From these and additional observations with RNase B, which
      contains high mannose-type oligosaccharides at Asn-34, it is clear that the
      protein moieties of these glycoproteins markedly influence the presentation of
      the oligosaccharides such that biological specificity is mediated by the commonly
      occurring high mannose-type oligosaccharides in the context of specific carrier
      proteins.

PMID- 8157688
TI  - DNA distortion and nucleation of local DNA unwinding within sigma-54 (sigma N)
      holoenzyme closed promoter complexes.
AB  - The sigma N (sigma 54) RNA polymerase holoenzyme has the distinctive property of
      binding to promoters to form a closed promoter complex, which only isomerizes to
      the open complex when acted upon by an enhancer binding activator protein. We
      probed promoter complexes that form between sigma N and its holoenzyme with the
      conformationally sensitive footprinting reagents ortho-copper phenanthroline,
      potassium permanganate, and diethylpyrocarbonate. Results from these experiments
      indicate that the contacts sigma N makes at the -12 promoter element are
      necessary to promote a local DNA distortion immediately adjacent to this promoter
      element when the holoenzyme but not sigma N alone binds promoter DNA. Complexes
      in which this local distortion is not detected are not activatable, and the
      altered DNA conformation is diminished in the activated complex. We propose that
      a barrier to open complex formation in the sigma N holoenzyme closed complex is
      at some step or steps after the initial nucleation of DNA strand separation,
      which is detected as an altered DNA conformation stably maintained within the
      closed complex. Thus the activator protein may promote a conformational change in
      the sigma N holoenzyme to allow propagation of the altered DNA conformation,
      probably local unwinding, which we propose is necessary for formation of the
      melted DNA state, characteristic of the open promoter complex.

PMID- 8157689
TI  - Hepatic lipase induces the formation of pre-beta 1 high density lipoprotein (HDL)
      from triacylglycerol-rich HDL2. A study comparing liver perfusion to in vitro
      incubation with lipases.
AB  - High density lipoprotein subfractions with a pre-beta migration play a key role
      in the reverse cholesterol transport. The origin of these particles is not yet
      clearly defined. We propose to verify a possible origin of these particles during
      the catabolism of high density lipoprotein2 (HDL2) by hepatic lipase using two
      different models. A rat liver perfusion of native human HDL2 in the presence of
      heparin induced, after 30 min, the formation of the pre-beta 1 HDL subspecies.
      Human HDL2 enriched with triacylglycerols, perfused in the same conditions, led
      after 15 min to an enhanced production of this pre-beta 1 HDL population, as
      compared with the results obtained with native HDL2. A reduction of the alpha
      HDL2 fraction was also evident. After perfusion, a similar formation of pre-beta
      1 HDL from triacylglycerol-rich HDL2 was observed in absence of heparin. When
      these HDL2 were incubated in vitro for 120 min at 37 degrees C in the presence of
      partially purified rat hepatic lipase, the appearance of pre-beta 1 HDL was again
      found and associated with a decrease in size of the remaining alpha-HDL
      subfractions as compared with original HDL2. On the contrary, the incubation of
      the same HDL2 with snake venom phospholipase A2 produced no pre-beta HDL. These
      results evidence the role of the triacylglycerol lipase activity of hepatic
      lipase in the formation of pre-beta 1 HDL from triacylglycerol-rich HDL2.

PMID- 8157690
TI  - Substitution of tyrosine 293 of GLUT1 locks the transporter into an outward
      facing conformation.
AB  - Tyrosines 292 and 293 in the mammalian glucose transporter GLUT1 have been
      substituted by either isoleucine or phenylalanine. Chinese hamster ovary clones
      that were transfected with Tyr-292-->Ile, Tyr-292-->Phe, Tyr-293-->Ile, and Tyr
      293-->Phe constructs of GLUT1 were shown, by Western blotting and cell surface
      carbohydrate labeling, to have expression levels that were comparable with the
      wild type. The Vmax for 2-deoxy-D-glucose transport was markedly reduced only as
      a result of the Tyr-293-->Ile mutation. The ability of the Tyr-293-->Ile mutated
      GLUT1 to bind the exofacial ligand 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3
      bis-(D-mannos- 4-yloxy)-2- propylamine (ATB-BMPA) and the endofacial ligand
      cytochalasin B were assessed by photolabeling procedures. The ability to bind the
      bis-mannose compound was unimpaired, whereas the ability to bind cytochalasin B
      was totally abolished, and the level of labeling was lower than in the
      nontransfected clone. Affinities of the wild-type and Tyr-293-->Ile GLUT1 for D
      glucose, the exofacial ligands (ATB-BMPA and 4,6-O-ethylidene-D-glucose), and the
      endofacial ligand (cytochalasin B) were assessed by the ability of these agents
      to displace the radioactive ATB-BMPA photolabel. These data indicated that the
      Tyr-293-->Ile substitution produced no change in the affinity for D-glucose, a
      relatively small enhancement in the affinity for exofacial ligands, but a large
      approximately 300-fold reduction in affinity for cytochalasin B, suggesting that
      the mutated GLUT1 is locked in an outward facing conformation. The observation
      that the Tyr-293-->Ile mutant transporter can bind nontransported C4 and C6
      substituted hexose analogues but cannot catalyze transport is interpreted as
      indicating that Tyr-293 is involved in closing the exofacial site around C4 and
      C6 of D-glucose in the transport catalysis process.

PMID- 8157691
TI  - Self-assembly into fibrils of collagen II by enzymic cleavage of recombinant
      procollagen II. Lag period, critical concentration, and morphology of fibrils
      differ from collagen I.
AB  - A recently developed recombinant system for synthesis of human procollagen II by
      stably transfected host cells was used to prepare adequate amounts of protein to
      study the self-assembly of collagen II into fibrils. The procollagen II was
      cleaved to pCcollagen II by procollagen N-proteinase (EC 3.4.24.14), the
      pCcollagen II was chromatographically purified, and the pCcollagen II was then
      used as a substrate to generate collagen II fibrils by cleavage with procollagen
      C-proteinase. The kinetics for assembly of collagen II fibrils were similar to
      those observed previously for the self-assembly of collagen I in that a distinct
      lag phase was observed followed by a sigmoidal propagation phase. However, under
      the same experimental conditions, the lag time for assembly of collagen II
      fibrils was 5-6-fold longer, and the propagation rate for collagen II fibrils was
      about 30-fold lower than for collagen I fibrils. The relatively long lag time for
      the assembly of collagen II into fibrils made it possible to demonstrate that
      most of the conversion of pCcollagen II to collagen II occurred in the solution
      phase. The critical concentration at 37 degrees C for collagen II was about 50
      fold greater than the critical concentration for collagen I. The Gibbs free
      energy change for the assembly of collagen II into fibrils was -40 kJ/mol, a
      value that was about 14 kJ/mol less than the free energy change for collagen I
      and about the same as the free energy change for the homotrimer of collagen I.
      Dark-field light microscopy and negative-staining electron microscopy
      demonstrated that the collagen II fibrils were thin and formed network-like
      structures. The results demonstrated, therefore, that the structural information
      of the monomer is sufficient to explain the characteristically small diameters
      and arcade-like geometry of collagen II fibrils found in cartilage and other
      tissues.

PMID- 8157693
TI  - Control of glycogen synthase and phosphorylase by amylin in rat skeletal muscle.
      Hormonal effects on the phosphorylation of phosphorylase and on the distribution
      of phosphate in the synthase subunit.
AB  - The effects of amylin and insulin on the phosphorylation of glycogen synthase and
      phosphorylase were investigated using rat diaphragms incubated with 32Pi. Muscles
      were incubated with insulin (200 nM) or amylin (200 nM) for 30 min before
      extracts were prepared. The 32P contents of the enzymes were determined after
      immunoprecipitation and SDS-polyacrylamide gel electrophoresis. Amylin increased
      both the activity ratio (-AMP/+AMP) and the 32P content of phosphorylase by
      approximately 2-fold. Insulin alone was without significant effect on
      phosphorylase, but insulin blocked the effect of amylin on increasing the
      phosphorylation of phosphorylase. Insulin increased the glycogen synthase
      activity ratio (low glucose-6-P/high glucose-6-P) by approximately 80%. Amylin
      decreased this ratio from 0.14 to 0.08 and increased the phosphorylation of
      synthase by approximately 40%. To investigate changes in phosphorylation of
      different sites in the synthase, the enzyme was subjected to exhaustive
      proteolysis with trypsin, and 32P-labeled fragments were separated by reverse
      phase high performance liquid chromatography. Insulin decreased the 32P contents
      of sites 3(a+b+c) and 2(a+b), which appears to account for the increase in
      synthase activity. Amylin increased phosphorylation of sites 1a, 1b, and
      3(a+b+c), but not sites 2(a+b). With insulin plus amylin, phosphorylation of none
      of the sites was significantly changed. The results indicate that the effects of
      amylin on glycogen synthase must involve more than activation of cAMP-dependent
      protein kinase, as this kinase phosphorylates site 2 and does not phosphorylate
      sites 3(a+b+c).

PMID- 8157692
TI  - Zinc finger domains and phorbol ester pharmacophore. Analysis of binding to
      mutated form of protein kinase C zeta and the vav and c-raf proto-oncogene
      products.
AB  - The phorbol ester binding domain consists of a cysteine-rich region with a
      postulated consensus sequence for binding that includes 15 amino acids (Ahmed,
      S., Kozma, R., Lee, J., Monfries, C., Harden, N., and Lim, L. (1991) Biochem. J.
      280, 233-241). In PKC zeta, the only PKC isoform lacking phorbol ester binding,
      this region differs in a single residue from the consensus (proline in position
      11 of the motif). Restoration of this proline by site-directed mutagenesis of PKC
      zeta does not restore binding of either [3H]phorbol 12,13-dibutyrate or of the
      ultrapotent ligand [3H]bryostatin 1, suggesting that even a low affinity ligand
      interaction is absent. In addition, the vav and c-raf proto-oncogene products,
      proteins that possess cysteine-rich regions with high homology to PKC isozymes
      and other phorbol ester receptors, are unable to bind any of these ligands.
      Instead, all of these cysteine-rich regions bind zinc. Our results suggest that
      other amino acids besides those postulated for the consensus must be necessary
      for ligand binding and argue against direct modulation of PKC zeta, Vav, and c
      Raf by phorbol esters.

PMID- 8157694
TI  - Conformation of Ca(2+)-ATPase in two crystal forms. Effects of Ca2+,
      thapsigargin, adenosine 5'-(beta, gamma-methylene)triphosphate), and
      chromium(III)-ATP on crystallization.
AB  - The structure of Ca(2+)-ATPase has been studied by electron microscopy of two
      different crystal forms: one tubular form induced by vanadate in native
      sarcoplasmic reticulum (SR) membranes and another multilamellar form grown from
      detergent-solubilized SR. To determine the conformation of Ca(2+)-ATPase within
      each crystal form, the respective effects of Ca2+, thapsigargin, adenosine 5'
      (beta, gamma-methylene)triphosphate) (AMP-PCP), and chromium(III) (Cr-ATP) on
      crystallization have been studied. Vanadate-induced tubes were prevented from
      forming by micromolar Ca2+, but if preformed in the absence of Ca2_, millimolar
      Ca2+ was required to disrupt these crystals. Thapsigargin promoted tube formation
      even in the presence of 10 mM Ca2+. Neither AMP-PCP nor Cr-ATP prevented tube
      formation, and the Ca2+ sensitivity of tube formation from Cr-ATP-inhibited SR
      was identical to controls. Multilamellar crystals required at least 0.2 mM Ca2+
      and were prevented from forming by thapsigargin, AMP-PCP, or Cr-ATP. It is
      concluded that helical tubes are composed of the Ca(2+)-free, dephosphorylated
      conformation (E), and the nucleotide-bound conformation (E-ATP) is also
      tolerated. In contrast, multilamellar crystals are composed of the Ca(2+)-bound
      conformation (E.Ca2) and do not tolerate nucleotide binding. Thus, comparison of
      structures obtained from the two crystal forms should reveal physiologically
      relevant conformational differences.

PMID- 8157695
TI  - Self-assembly of collagen I from a proband homozygous for a mutation that
      substituted serine for glycine at position 661 in the alpha 2(I) chain. Possible
      relationship between the effects of mutations on critical concentration and the
      severity of the phenotype.
AB  - Procollagen I was isolated from cultured skin fibroblasts from a proband who was
      homozygous for a mutation in the COL1A2 gene that substituted a serine codon for
      a glycine codon at position 661 of the alpha 2(I) chain. The procollagen I was
      cleaved to pCcollagen I by procollagen N-proteinase and the pCcollagen I was used
      as a substrate for assay of self-assembly of collagen I into fibrils. The mutated
      pCcollagen I was cleaved to collagen I by procollagen C-proteinase at the same
      rate as control pCcollagen I. However, self-assembly of the mutated collagen I
      had a lag period that was 15-fold greater than the lag period observed with
      normal collagen I under the same conditions. Also, self-assembly of the mutated
      collagen I had a propagation rate of about one-fourth of the propagation rate of
      normal collagen I. In addition, the critical concentration for fibril assembly
      was slightly increased. Rotary shadowing electron microscopy of the mutated
      procollagen I did not reveal any increased flexibility of the triple helix as was
      seen previously with two mutated procollagens I in which there were substitutions
      of cysteine for glycine residues in the alpha 1(I) chain (Vogel, B. E., Doelz,
      R., Kadler, K. E., Hojima, Y., Engel, J., and Prockop, D. J. (1988) J. Biol.
      Chem. 263, 19249-19255; Lightfoot, S. J., Holmes, D. F., Brass, A., Grant, M. E.,
      Byers, P. H., and Kadler, K. E. (1992) J. Biol. Chem. 267, 25521-25528). However,
      morphometric analysis by dark-field light microscopy and electron microscopy
      showed that the fibrils formed from the mutated collagen I appeared thicker in
      diameter than the fibrils formed from the normal collagen I. Comparison of the
      results with similar data on four mutated procollagens previously studied raised
      the possibility that mutations which markedly increase the critical concentration
      of fibril assembly produce more severe phenotypes than mutations which change
      other parameters of fibril assembly.

PMID- 8157696
TI  - Class I histocompatibility molecule association with phosphorylated calnexin.
      Implications for rates of intracellular transport.
AB  - Recent studies have shown that the endoplasmic reticulum (ER)-resident protein,
      calnexin, associates with class I major histocompatibility complex (MHC)
      molecules early in their biosynthesis. It has been suggested that calnexin
      participates in the assembly of class I MHC molecules or in the retention within
      the ER of unassembled class I molecules. We have examined the role of
      phosphorylation of calnexin in its association with mouse class I MHC molecules.
      We show that phosphocalnexin associates with H-2Ld and H-2Db molecules but not
      with H-2Kb and H-2Dd molecules, although calnexin-H-2Kb association can be
      demonstrated. These observations are interesting in light of the fact that H-2Kb
      and H-2Dd molecules are transported out of the ER more rapidly than are H-2Ld and
      H-2Db molecules. H-2Ld and H-2Db molecules differ in amino acid sequence only in
      their membrane-distal alpha 1 and alpha 2 domains. Nevertheless, the affinity of
      phosphocalnexin for H-2Ld is greater than its affinity for H-2Db. Furthermore, H
      2Db becomes endoglycosidase H-resistant more slowly in cells in which it
      associates with phosphocalnexin than in cells in which it does not. Ca2+
      ionophore A23187 prevents association of phosphocalnexin with H-2Ld molecules in
      vivo but does not cause the disruption of phosphocalnexin-H-2Ld complexes after
      they have formed. A23187 does not prevent assembly of H-2Ld-beta 2-microglobulin
      (beta 2-m) heterodimers. Furthermore, phosphocalnexin is found associated with H
      2Ld molecules regardless of their state of assembly with beta 2-m and antigenic
      peptide. These results suggest that phosphocalnexin association with class I MHC
      molecules does not play a role in assembly of the class I MHC-beta 2-m-peptide
      complex nor in preventing release of unassembled class I molecules from the ER
      but may otherwise influence their rate of transport through the ER.

PMID- 8157697
TI  - Purification and characterization of 240-kDa cGMP-dependent protein kinase
      substrate of vascular smooth muscle. Close resemblance to inositol 1,4,5
      trisphosphate receptor.
AB  - The 240-kDa, cGMP-dependent protein kinase substrate protein obtained from
      porcine aortic smooth muscle, whose phosphorylation was closely associated with
      stimulation of plasma membrane Ca(2+)-pump ATPase (Yoshida, Y., Sun, H.-T., Cai,
      J.-Q., and Imai, S. (1991) J. Biol. Chem. 266, 19819-19825), was purified to near
      homogeneity by three successive chromatographic runs with calmodulin-,
      concanavalin A-, and heparin-Sepharose columns from microsomes solubilized with
      Triton X-100. The purified protein was found to bind inositol 1,4,5-trisphosphate
      (InsP3) in a specific, heparin-inhibitable manner with a Kd of 2.0 nM and Bmax of
      450 pmol/mg protein (the binding of inositol 1,3,4,5-tetrakisphosphate was much
      weaker). In sedimentation experiments on a linear sucrose density gradient the
      InsP3 binding activity was always with the 240-kDa protein. Protein kinase G
      phosphorylated the InsP3 receptor purified from the rat cerebellum as well as the
      240-kDa protein. Sialic acid content of the protein measured with Limulus
      polyphemus agglutinin was not significantly different from that of the cerebellar
      InsP3 receptor. Thus, 240-kDa protein closely resembles InsP3 receptor and may be
      a type of InsP3 receptor. The only difference was the behavior on SDS
      polyacrylamide gel electrophoresis. The 240-kDa protein presented itself as two
      polypeptides with similar but slightly differing M(r) values, both of which were
      phosphorylated by protein kinase G.

PMID- 8157698
TI  - Negative modulator of the rat D2 dopamine receptor gene.
AB  - The rat D2 dopamine receptor gene is transcribed from a TATA-less promoter that
      has an initiator-like sequence and several putative Sp1 binding sites. The main
      activator of this gene is between nucleotides -75 and -29, and a strong negative
      modulator is located between bases -217 and -76 (Minowa, T., Minowa, M. T., and
      Mouradian, M. M. (1992) Biochemistry 31, 8389-8396). In the present
      investigation, a small deletion series within this negative modulator fused with
      the reporter gene for chloramphenicol acetyltransferase was used to transfect the
      D2-expressing cells, NB41A3. Two cis-acting functional DNA sequences were
      identified: a 41-base pair segment between nucleotides -116 and -76 (D2Neg-B),
      which decreased transcription from the D2 promoter by about 45%, and a 26-base
      pair segment between nucleotides -160 and -135 (D2Neg-A), which, in the presence
      of the downstream negative modulator, reduced transcription down to the level of
      a promoterless vector. DNase I footprinting, gel mobility shift, and competitive
      cotransfection experiments suggested that D2Neg-A functions without trans-acting
      factors, whereas D2Neg-B interacts with nuclear factors at its Sp1 binding
      sequences. Gel supershift with anti-Sp1 antibody and UV cross-linking experiments
      revealed that a novel 130-kDa factor as well as Sp1 interact with D2Neg-B in
      NB41A3 cells. This novel protein recognizing Sp1 binding sequences in the D2 gene
      negative modulator is also found in nuclear extract from the rat striatum.

PMID- 8157699
TI  - Characterization of the genomic structure, chromosomal location, promoter, and
      development expression of the alpha-globin transcription factor CP2.
AB  - We recently cloned murine and human cDNAs that encode CP2, a cellular
      transcription factor that interacts with the alpha-globin promoter as well as
      with additional cellular and viral promoter elements. We have now characterized
      the genomic structure, chromosome location, promoter, and expression pattern of
      the factor. Genes for the murine and human mRNAs contained 16 and 15 exons,
      respectively. Both genes spanned approximately 30 kilobases of chromosomal DNA,
      and among coding exons, all exon/intron boundaries were conserved. The human gene
      for CP2 was found to reside on chromosome 12 while the murine gene mapped to the
      distal end of chromosome 15, near Gdc-1, Wnt-1, and Rarg, a region syntenic with
      human chromosome 12. The murine and human promoters initiated mRNAs at multiple
      start sites in a conserved region that spanned more than 450 nucleotides. Lastly,
      a study of the pattern of CP2 gene expression showed that the factor was
      expressed in all adult and fetal murine tissues examined from at least day 9.5 of
      development.

PMID- 8157700
TI  - Overexpression of human lipoprotein lipase in transgenic mice. Resistance to diet
      induced hypertriglyceridemia and hypercholesterolemia.

PMID- 8157701
TI  - Health care expenditures for people with diabetes mellitus, 1992.
AB  - The purpose of this report is to estimate diabetes prevalence and annual health
      care costs for people with diabetes in 1992, compare average annual costs for
      diabetics and nondiabetics, and estimate the portion of total U.S. health care
      expenditures incurred by people with the disease. Data from the 1987 National
      Medical Expenditure Survey were used to estimate diabetes prevalence and health
      care expenditures for diabetics in 1992. Diabetics were identified based on self
      reports of a physician diagnosis of diabetes, a history of taking diabetic
      medications, or an encounter with the health care system specifically related to
      diabetes. Identified diabetics were classified as confirmed if they had a history
      of taking diabetic medications, had a diabetes-specific encounter with the health
      care system, or purchased diabetic equipment. Estimates of diabetes prevalence
      and health care expenditures were calculated separately for identified and
      confirmed diabetics using the National Medical Expenditure Survey database. Total
      health care expenditures included costs associated with inpatient hospital care,
      outpatient hospital care, office visits to a physician or other provider,
      emergency room visits, home health care, prescription drugs, dental care, and
      durable medical equipment purchases. We estimate that percapita annual health
      care expenditures in 1992 were more than three times greater for diabetics
      ($9,493) than for nondiabetics ($2,604). Percapita expenditures for confirmed
      diabetics ($11,157) were more than four times greater than for nondiabetics. In
      1992, diabetics constituted 4.5% of the U.S. population but accounted for 14.6%
      of total U.S. health care expenditures ($105 billion). Confirmed diabetics
      constituted 3.1% of the U.S. population but accounted for 11.9% of total U.S.
      health care expenditures ($85 billion). This study found that health care
      expenditures for people with diabetes constituted about one in seven health care
      dollars spent in 1992. Health care reform and insurers should take note of these
      findings and structure benefit packages to promote care likely to reduce the
      costs of caring for diabetics.

PMID- 8157702
TI  - Clinical review 56: Nonclassic adrenal hyperplasia: current concepts.

PMID- 8157703
TI  - Detrimental skeletal effects of thyrotropin suppressive doses of thyroxine: fact
      or fantasy?

PMID- 8157704
TI  - Carefully monitored levothyroxine suppressive therapy is not associated with bone
      loss in premenopausal women.
AB  - We measured total body and regional (lumbar spine, femoral neck, Ward's triangle,
      and trochanter) bone mineral density (BMD) in 47 premenopausal women chronically
      treated with suppressive doses of levothyroxine (L-T4). Treatment was
      administered to 7 patients with nontoxic goiter or, after thyroidectomy, to 38
      patients with differentiated thyroid cancer and 2 with nontoxic goiter. Patients
      were followed at our institution and treated with the minimal amount of L-T4
      necessary to suppress TSH. At the time of evaluation, free T3 was normal in all
      cases, whereas free T4 was increased in 17 (36.2%). The mean daily dose of L-T4
      was 154.3 +/- 5 micrograms, and the mean duration of treatment was 10.1 yr. We
      found no significant difference between patients and age- and weight-matched
      controls in BMD at any site of measurement. BMD was not correlated with duration
      of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free
      T3, and osteocalcin. There was no difference between patients and controls in
      serum total calcium, intact PTH, osteocalcin, or carboxy-terminal cross-linked
      telopeptide of type I collagen or in the concentrations of two markers of thyroid
      hormone action (sex hormone-binding globulin and amino-terminal propeptide of
      type III procollagen). Our data suggest that L-T4 suppressive therapy, if
      carefully carried out and monitored, using the smallest dose necessary to
      suppress TSH secretion has no significant effect on bone metabolism or bone mass.

PMID- 8157705
TI  - When is a thyroid nodule a sporadic medullary carcinoma?

PMID- 8157706
TI  - Routine measurement of serum calcitonin in nodular thyroid diseases allows the
      preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma.
AB  - To assess whether routine measurement of serum calcitonin (CT) could improve the
      preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC), 1385
      consecutive patients presenting for nodular thyroid disease during the year 1991
      were submitted to serum CT determination and fine needle aspiration cytology
      (FNAC). The clinical diagnosis was nontoxic nodular goiter in 1197 (86.4%)
      patients, toxic multinodular goiter in 65 (4.7%), autonomously functioning
      thyroid nodule (AFTN) in 64 (4.6%), and autoimmune thyroid disease (Graves'
      disease or Hashimoto's thyroiditis) with nodule(s) in 59 (4.3%). As controls, 177
      patients with nonnodular thyroid disease and 32 normal subjects were also
      studied. Patients with FNAC suspicious of any kind of thyroid carcinoma and
      patients with elevated basal and pentagastrin-stimulated serum CT, regardless of
      the results of FNAC, were submitted to surgery. Eight (0.57%) patients (7 with
      nontoxic nodular goiter and 1 with AFTN) had elevated basal serum CT levels,
      ranging between 55-10,000 pg/mL. The pentagastrin test was abnormal in all of
      them. FNAC was suggestive of MTC in 2, thyroid carcinoma in 1, benign nodule in
      3, and inadequate in 2. By histology, immunohistochemistry, and Northern blot
      analysis of total tumor RNAs, MTC was confirmed in all patients, including the 1
      with AFTN, who had the association of microfollicular adenoma and a small MTC in
      the same lobe. After surgery, serum CT decreased to undetectable levels in 7
      patients and remained undetectable in 6 of them during a mean follow-up of 22
      months, although 1 of them had a positive response to pentagastrin. Forty-four
      patients in the group with normal serum CT levels had FNAC suspicious for
      differentiated thyroid carcinoma and were treated by surgery. Differentiated
      thyroid carcinoma, mostly papillary, was confirmed at histology in 43 subjects
      (3.1% of all thyroid nodules). In conclusion, the results of our study indicate
      that serum CT measurement is useful for the screening of sporadic MTC in patients
      with thyroid nodule(s). The prevalence of MTC, diagnosed by serum CT measurement
      in a 12-month period, among an unselected series of 1385 patients with nodular
      thyroid disease was surprisingly high: 0.57% of all thyroid nodules and 15.7% of
      all thyroid carcinomas. Serum CT measurement was superior to FNAC in suggesting
      the diagnosis of MTC and was devoid of falsely positive results. Increasing the
      diagnostic accuracy helped the surgeon to perform more radical treatment of MTC,
      thus achieving frequent normalization of postoperative serum CT levels. Whether
      this result indicates definitive cure remains to be established on the basis of
      longer follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8157707
TI  - Renal 11 beta-hydroxysteroid dehydrogenase activity is enhanced by ramipril and
      captopril.
AB  - Changes of renal 11 beta-hydroxysteroid dehydrogenase activity may contribute to
      variations of sodium excretion by modulating inactivation of cortisol or
      corticosterone and thus their access to mineralocorticoid receptors. Angiotensin
      converting enzyme inhibitors enhance sodium excretion but by mechanisms still
      incompletely understood. To test the hypothesis that the angiotensin-converting
      enzyme inhibitors ramipril and captopril act in part by enhancing renal 11 beta
      hydroxysteroid dehydrogenase activity, the effects of these agents in slices of
      rat renal outer medulla were examined. Conversion of 3H-corticosterone to 3H-11
      dehydrocorticosterone was 58% greater in tissue from fasted rats than from fed
      rats (mean +/- SE 2467 +/- 146 vs. 1584 +/- 102 pmol/mg protein.h, P < 0.01).
      Incubation of tissue from fed rats with physiological concentrations of
      ramiprilat, the active form of ramipril, enhanced activity (1497 +/- 76) to
      fasted levels (2323 +/- 120, P < 0.02). Captopril had a similar in vitro effect
      (1557 +/- 92 to 2109 +/- 116, P < 0.01). Ramipril given in vivo to fed rats also
      increased activity to fasted levels (1716 +/- 101 to 2737 +/- 396, P < 0.05).
      Angiotensin II incubated with renal tissue from fasted rats suppressed activity
      to fed levels, but this effect was prevented by the presence of ramiprilat. Both
      ramipril and captopril enhance renal 11 beta-hydroxysteroid dehydrogenase
      activity, and this effect is only partly explained by limitation of endogenous
      angiotensin II production.

PMID- 8157708
TI  - Differential release of proopiomelanocortin-derived peptides from the human
      pituitary: evidence from a panel of two-site immunoradiometric assays.
AB  - In humans, proopiomelanocortin (POMC) and the peptides derived from it have been
      individually identified in plasma under differing conditions. However, direct
      quantitative comparison has proved difficult because of the limitations of RIAs.
      Using a panel of monoclonal antibodies recognizing different regions of POMC, we
      have developed specific two-site immunoradiometric assays (IRMAs) for the ACTH
      precursors (POMC and pro-ACTH), ACTH, beta-lipotropin (beta LPH), beta-endorphin
      (beta EP), and the N-terminal POMC fragment (N-POC). We have quantified these
      peptides directly in plasma from normal subjects under basal conditions and in
      response to different regulatory factors. Basal levels of ACTH precursors, 5-40
      pmol/L, were greater than or equal to ACTH, less than 0.9-11.3 pmol/L; N-POC, 5.6
      16.8 pmol/L; beta LPH, 2.5-6.7 pmol/L; and beta EP less than or equal to 1.7
      pmol/L. ACTH, N-POC, beta LPH, and beta EP levels increased in parallel in
      response to metyrapone (n = 8) and decreased in response to dexamethasone (n =
      8), whereas ACTH precursor concentrations did not respond. After human CRH
      administration, peripheral concentrations of ACTH, N-POC, and beta LPH showed
      similar increments (median increment, 163%, 145%, and 172%, respectively; n = 6).
      POMC peptide responses to human CRH were also assessed in inferior petrosal
      sinuses draining the pituitary in 20 patients with pituitary-dependent Cushing's
      disease. In these patients, the increment in ACTH after CRH exceeded that in ACTH
      precursors by 4-fold (median, 459% and 96%). An increase in the ratios of ACTH/N
      POC and ACTH/beta LPH was also apparent after CRH stimulation. The increment in
      beta EP after CRH always exceeded the increments in POMC and beta LPH. In
      summary, these data suggest that significant concentrations of ACTH precursors
      are present in the circulation of normal subjects, that ACTH precursors are not
      regulated in the same way as the processed POMC peptides, and that ACTH and beta
      EP are preferentially released from the pituitary in response to CRH.

PMID- 8157709
TI  - H-ras mutations in human pituitary carcinoma metastases.
AB  - Molecular mechanisms of pituitary tumorigenesis were studied using Polymerase
      chain reaction-single stranded conformational polymorphism with DNA sequencing to
      identify potential mutations in the ras protooncogenes and the tumor suppressor
      gene p53 in invasive pituitary adenomas and carcinomas. Sequencing of exons 5
      through 8 of the p53 gene revealed no mutations, nor were mutations detected in
      the N- or K-ras protooncogenes in four of the carcinomas and their respective
      metastatic deposits. Point mutations of H-ras however, were identified in three
      distant metastatic pituitary tumor secondaries, but not in their respective
      primary pituitary carcinomas, or in six invasive adenomas. Two of the mutations
      included a G to C substitution at codon 12, and a G to A substitution at codon
      18, resulting in a glycine to arginine, and an alanine to threonine change at
      these amino acids, respectively. A third mutation involved a single base pair
      (adenine) deletion in codon 3 of H-ras which causes a frame shift, resulting in a
      termination signal at codon 19. These results suggest that point mutations in p53
      and ras are not associated with pituitary tumorigenesis, however, point mutations
      of the H-ras gene may be important in the formation and or growth of pituitary
      metastases. This observed genomic instability will be of value in predicting the
      potential metastatic behavior of these aggressive pituitary tumors.

PMID- 8157710
TI  - Interleukin-1 system in the materno-trophoblast unit in human implantation:
      immunohistochemical evidence for autocrine/paracrine function.
AB  - Interleukin-1 receptor type I, IL-1 beta, IL-1 receptor antagonist, and human
      macrophages were immunohistochemically localized in the villous trophoblast,
      maternal-trophoblast interphase, and maternal decidua during early human
      implantation. Immunostaining for IL-1 receptor type I was present in the
      syncytiotrophoblast and hyperplastic endometrial glands in the maternal decidua.
      Immunoreactive IL-1 beta was present in the villous cytotrophoblast,
      syncytiotrophoblast, intermediate trophoblast, and maternal stromal decidual
      cells. IL-1 receptor antagonist staining was observed in the glandular
      endometrium of the maternal decidua and in isolated cells located inside the
      chorionic villi, intervillous space, and maternal decidua. Mature human
      macrophages, as defined by both CD/68+ and HAM56+, were present in the chorionic
      villi, maternal blood of intervillous space, and maternal decidua. Co
      localization studies demonstrated that macrophages in all of the reported
      locations also stained for immunoreactive IL-1 beta. Our results show the shared
      presence in maternal and embryonic tissues of this receptor-agonist-antagonist
      system during early human implantation. This finding supports an
      autocrine/paracrine role for the IL-1 system in human implantation.

PMID- 8157711
TI  - Physiological levels of estradiol stimulate plasma high density lipoprotein2
      cholesterol levels in normal men.
AB  - Premenopausal women have a lower risk of coronary artery disease than men or
      postmenopausal women; estrogens are thought to contribute to this lower risk.
      Administration of exogenous estrogen to post-menopausal women increases plasma
      high density lipoprotein (HDL) cholesterol and may reduce mortality from coronary
      disease in users. Although many investigations have examined the roles of
      estrogen in the regulation of lipoproteins in women, little attention has been
      directed to estrogen regulation of lipids in men. We designed a paradigm to study
      the role of physiological levels of estradiol (E2) on plasma lipoproteins in
      healthy men. We used a GnRH antagonist, Nal-Glu, to suppress endogenous steroid
      hormones in healthy men. We then administered testosterone (T) enanthate (100 mg,
      im, weekly) to restore T levels to the baseline range, and we administered an
      aromatase inhibitor, testolactone (Teslac), to prevent the normal conversion of T
      to E2, thereby producing a selective estrogen deficiency state in normal young
      men. As controls, we administered Nal-Glu and T along with placebo Teslac to a
      separate group of men; a third group of men received all placebo medications. We
      found that in men who received Nal-Glu plus T plus Teslac, E2 levels were
      profoundly suppressed during treatment, whereas T levels remained in the baseline
      range. Plasma HDL cholesterol, particularly, the HDL2 fraction, decreased
      significantly in response to the low serum E2 level. Plasma apoprotein-AI levels
      also decreased significantly. Plasma LDL and triglyceride levels did not change.
      All hormone and lipoprotein parameters returned to baseline within 4 weeks after
      treatment ended. In men who received Nal-Glu plus T, plasma HDL and apoprotein-AI
      decreased, but these decreases did not achieve statistical significance. Only a
      small decrease in HDL2 cholesterol was seen in these men. There were no hormonal
      or lipid changes in the placebo group. We conclude that in men, physiological
      levels of E2 are important in maintaining plasma levels of HDL cholesterol,
      especially the HDL2 fraction. These observations suggest that estrogen, in the
      amount normally produced in men, may offer some degree of protection against
      cardiovascular disease in males, as they do in women.

PMID- 8157712
TI  - Thyrotropic activity of basic isoelectric forms of human chorionic gonadotropin
      extracted from hydatidiform mole tissues.
AB  - hCG is known to have thyroid-stimulating activity and may cause hyperthyroidism
      in patients with trophoblastic diseases. hCG occurs in normal and molar pregnancy
      with breaks or nicks in the alpha- or beta-subunit peptide linkage and with
      substantial heterogeneity in the composition and degree of branching within the
      oligosaccharide side-chains. The bioactivity of hCG is markedly influenced by
      these structural variations. We purified hCG from five hydatidiform moles, using
      chromatofocusing separation after gel filtration. The hCG molecules were
      fractionated according to their isoelectric points, with a linear pH gradient
      from 3.2-6.1 and a final 1.0 mol/L NaCl step elution. The hCG immunoreactivity of
      each fraction was measured by RIA, and the thyroid-stimulating activity of hCG
      was determined by means of the cAMP response in Chinese hamster ovary cells
      expressing functional human TSH receptors (Chinese hamster ovary-JP09 cells). The
      chromatofocusing profile showed that hCG from the moles was eluted in six or
      seven major peaks at pH 6.1, 5.5, 5.3, 4.8, 3.8, and 3.2 and with 1.0 mol/L NaCl,
      whereas hCG extracted from serum of hydatidiform moles and standard hCG
      preparation CR-127 extracted from pregnancy urine showed only small peaks at pH
      greater than 5.3. Each fraction increased cAMP production significantly in
      Chinese hamster ovary-JP09 cells. The relative bioactivity/immunoreactivity,
      represented as the ratio of cAMP/hCG (picomoles per IU), was significantly higher
      in basic components (pI 6.1, 6.2 +/- 1.2; pI 5.5, 4.4 +/- 2.7; pI 5.3, 5.8 +/-
      0.3) than in hCG CR-127 (bioactivity/immunoreactivity, 0.42; P < 0.05). The
      difference in pI of each hCG isoform was attributable to the extent of
      sialylation; basic hCG isoforms contained less sialic acid by immunological
      detection using lectins. These results indicate that isoforms of hCG with more
      thyrotropic activity were produced by trophoblastic tissues in patients with
      hydatidiform mole. We speculate that these isoforms of hCG may be responsible for
      the hyperthyroidism in some patients with hydatidiform moles.

PMID- 8157713
TI  - Expression of thyrotropin receptor (TSH-R), thyroglobulin, thyroperoxidase, and
      calcitonin messenger ribonucleic acids in thyroid carcinomas: evidence of TSH-R
      gene transcript in medullary histotype.
AB  - We studied the expression of the TSH receptor (TSH-R), thyroglobulin (Tg),
      thyroperoxidase (TPO), and calcitonin (CT) genes in a total of 53 tissues from 30
      patients with thyroid carcinoma and from 9 patients with benign thyroid diseases.
      By Northern blot analysis of total RNA preparations, CT mRNA was expressed in all
      cases (n = 6) of medullary thyroid carcinoma (MTC). Surprisingly, 3 of them
      expressed the TSH-R mRNA, in association with the Tg and TPO mRNAs in 1. The
      presence of the TSH-R transcript in the neoplastic C-cells was confirmed in 1 MTC
      by in situ hybridization using a mixture of 3 oligonucleotide probes derived from
      dog TSH-R cDNA. With various degrees of expression, all differentiated thyroid
      carcinomas (20 papillary and 2 follicular) expressed TSH-R, Tg, and TPO, but not
      CT mRNAs. On the contrary, samples from 2 patients with anaplastic carcinoma did
      not express TSH-R, Tg, or TPO mRNA, but 1 of them expressed CT mRNA. All of the
      transcripts obtained from thyroid carcinomas (both primary and metastatic) were
      of the same size as the transcripts from normal or benign thyroid tissues, with
      the exception of 2 cases of differentiated thyroid cancer, in which TSH-R mRNA of
      lower mol wt (approximately 4.0 kilobases) was found in the absence of alteration
      in cDNA size and restriction map. The main conclusions of our study are that 1)
      the TSH-R gene is expressed in some MTC, which supports, at molecular level, the
      hypothesis of the existence of mixed follicular-medullary thyroid tumors; and 2)
      the expression of TSH-R, Tg, and TPO in undifferentiated thyroid cancer is lost.

PMID- 8157714
TI  - Inhibition of lysozyme synthesis by dexamethasone in human mononuclear
      leukocytes: an index of glucocorticoid sensitivity.
AB  - Glucocorticoids inhibit translation of the lysozyme gene. This effect may be the
      basis of an improved method of measuring glucocorticoid responsiveness in human
      tissues. We have compared lysozyme synthesis in various types of white blood
      cells and examined the specificity of inhibitory responses to various steroid
      hormones. The dose-related effects of the glucococorticoid receptor antagonist
      RU486 on dexamethasone responses were also assessed. Glucocorticoid receptor
      binding in mononuclear leukocytes (HML) was characterized by homologous
      displacement of [3H]dexamethasone and compared with the dose-related inhibitory
      effect of dexamethasone on lysozyme synthesis. Lysozyme activity was measured
      photometrically as the ability to cause lysis of Micrococcus lysodeikticus in the
      medium. The greatest effect of dexamethasone was observed after 72 h of culture.
      Qualitatively similar effects of dexamethasone were observed on cell lysozyme
      content and lysozyme activity in the medium, but for convenience, activity in
      medium, rather than cell content, was measured in subsequent assays. Lysozyme
      activities in various cell types prepared from the blood of healthy volunteers
      were ranked as follows: polymorphonuclear cells > monocytes > mononuclear cells >
      lymphocytes. However, dexamethasone inhibited lysozyme synthesis to a similar
      degree for all types. As mononuclear cells are more conveniently prepared in
      greater yield compared with other cells, this HML fraction formed the basis of a
      method of assessing glucocorticoid responsiveness and sensitivity. Lysozyme
      activity from HML was not significantly affected by incubation with 1 mumol/L
      estradiol, progesterone, dehydroepiandrosterone, or aldosterone. Dexamethasone
      and cortisol at 1 mumol/L both inhibited release by 45-50%. Although RU486 when
      added alone partially inhibited lysozyme activity, the same concentration (1
      mumol/L) antagonized glucocorticoid responses and shifted the IC50 and threshold
      values for the effect of dexamethasone from 1.2 nmol/L to more than 1 mumol/L and
      from less than 1.0 to 19 nmol/L, respectively. The equilibrium dissociation
      constants (Kd) for dexamethasone binding to the glucocorticoid receptor ranged
      from 2.8-12.5 nmol/L and were positively correlated with dexamethasone IC50
      values for lysozyme synthesis (r = 0.57; P = 0.002). In conclusion, the
      inhibition of lysozyme synthesis by dexamethasone in human mononuclear cells is a
      convenient and specific method of measuring responsiveness to glucocorticoids.

PMID- 8157715
TI  - HLA-DQB1-associated susceptibility that distinguishes Hashimoto's thyroiditis
      from Graves' disease in type I diabetic patients.
AB  - Insulin-dependent diabetes (IDDM) is frequently associated with autoimmune
      thyroid disease (ATD) within families. In these families, HLA polymorphism may
      modulate the susceptibility to each disease. Families with IDDM were further
      categorized as to the presence of ATD. IDDM-affected subjects from families
      without ATD were compared with subjects with ATD or with IDDM and ATD from
      IDDM/ATD families and with a control group. IDDM susceptibility in IDDM/ATD
      families was negatively associated with the presence of DQB1*0602 [relative risk
      (RR) = 0.038; P = 0.0001; corrected P (Pc) = 0.0005] and *0301 (RR = 0.3; P =
      0.002; Pc = 0.01) and positively associated with the presence of DQB1*0201 (RR =
      3.4; P = 0.0007; Pc = 0.0035) and *0302 (RR = 5; P = 0.0001; Pc = 0.0005),
      regardless of ATD. Compared with the IDDM-only group, the ATD-only group had an
      increased frequency of subjects with DQB1*0602 (RR = 0.14; P = 0.031), suggesting
      that the known IDDM-protective effect of this allele may be independent of
      susceptibility to ATD; however, this difference was not significant when the P
      value was correlated for the number of alleles tested. In these families,
      susceptibility to ATD was only associated with DQB1*0201 (RR = 5.71; P = 0.0043;
      Pc = 0.021). Among subjects with DQB1*0201, there was a weak negative association
      between the presence of DQB1*0302 on the second haplotype and Hashimoto's
      thyroiditis (RR = 0.237; P = 0.026; Pc > 0.05). We conclude that in IDDM/ATD
      families, IDDM-affected subjects are at risk for ATD, especially those carrying
      DQB1*0201. This risk may be influenced by the alleles carried on the second
      haplotype, with DQB1*0302 (or a closely linked gene) protecting from Hashimoto's
      thyroiditis and favoring Graves' disease.

PMID- 8157716
TI  - Familial congenital hypopituitarism with central diabetes insipidus.
AB  - Congenital hypopituitarism (CH) presenting with central diabetes insipidus is
      typically associated with midline facial deformities or ophthalmological
      abnormalities. We present three brothers with CH and central diabetes insipidus
      not associated with any of these predisposing conditions. All three subjects
      presented with clinical features typical for CH (neonatal hypoglycemia, short
      stature, protruding forehead, and microgenitalia). All had hypoplastic genitalia
      indicating in utero gonadotropin deficiency, and all had complete GH deficiency.
      One represented low levels of thyroid hormones and TSH, indicating central
      hypothyroidism. Water deprivation examination in two of the brothers demonstrated
      complete arginine vasopressin deficiency in one and partial deficiency in the
      other. Magnetic resonance imaging indicated absence of the pituitary stalk,
      severe hypoplastic anterior pituitary in all three brothers, and absence of any
      posterior pituitary gland in two of the three. The other sibling had an ectopic
      posterior pituitary. This first report of familial CH with central diabetes
      insipidus may represent a previously unknown midline anomaly and provide new
      insights into the genetic control of pituitary and hypothalamic development.

PMID- 8157717
TI  - Amplitude regulation of episodic release, in vitro biological to immunological
      ratio, and median charge of human chorionic gonadotropin in pregnancy.
AB  - In the present study, we examined the regulation of 24-h serum immunoreactive
      levels, in vitro biological to immunological (B/I) ratio, and median charge of
      circulating CG at the end of the first, second, and third trimesters of human
      gestation. Seven pregnant women were prospectively studied at 12-15, 23-26, and
      35-38 weeks of gestation. Blood was sampled every 20 min over a 24-h period, and
      serum CG concentrations were determined by RIA. Pulse detection and analysis of
      the 24-h rhythm of serum immunoreactive CG concentrations were carried out by the
      program Cluster and cosine curve fitting, respectively. The in vitro biological
      activity of circulating CG was determined by the mouse Leydig cell-testosterone
      production bioassay, and the median charge of its isoforms was determined by zone
      electrophoresis in agarose suspension. The immunoreactive levels of CG present at
      the end of each trimester of gestation fluctuated over a 24-h period; such
      variability exceeded that of the within-assay coefficient of variation of the CG
      RIA and could be resolved into a series of CG peaks and valleys. Although no
      trend in the number of peaks or valleys was systematically found in relation to
      gestational age, comparisons between the amplitude and area of the CG peaks
      revealed that these pulse parameters were significantly higher at 12-15 weeks
      than at 23-26 and 35-38 weeks of gestation. Cosine fits for 24-h rhythms revealed
      the existence of significant nyctohemeral profiles of serum CG levels in all
      women studied at 12-15 weeks, in four subjects at 23-26 weeks, and in six women
      at 35-38 weeks gestation. The time of acrophase was highly homogeneous only
      between 12-15 weeks of gestation, occurring between 1057-1452 h in six of the
      women. The in vitro B/I ratio of CG contained in serum pools from 12-15 weeks was
      significantly (P < 0.05) higher than that exhibited by CG during later
      gestational periods (B/I ratio at the end of first trimester, 1.14 +/- 0.14;
      second trimester, 0.87 +/- 0.22; third trimester, 0.79 +/- 0.12). hCG isoforms at
      12-15 weeks were more negatively charged than those circulating at 23-26 and 35
      38 weeks of gestation. There were no significant differences between the B/I
      ratio and the median charge of CG molecules from the second and third trimesters.
      We conclude that serial serum concentrations of CG throughout pregnancy show
      significant amplitude-modulated pulsatile release and nyctohemeral
      variations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8157718
TI  - Adrenergic regulation of lipolysis in fat cells from hyperthyroid and hypothyroid
      patients.
AB  - The influence of thyroid hormones on the adrenergic regulation of lipolysis was
      studied in isolated adipocytes removed from the gluteal region of hyper- and
      hypothyroid women and compared in adipocytes from euthyroid normal women.
      Noradrenaline significantly enhanced lipolysis in hyperthyroid patients, whereas
      noradrenaline inhibited lipolysis in hypothyroid patients compared to that in
      controls. Moreover, beta-adrenergic sensitivity and responsiveness were 10- and 2
      fold increased, respectively, in hyperthyroid patients. In hypothyroid patients,
      beta-adrenoceptor responsiveness was reduced by 50%, whereas beta-adrenergic
      sensitivity remained unchanged compared with that in controls. Furthermore, the
      alpha 2-adrenergic and adenosine-induced antilipolytic effects were similar in
      all thyroid states. The lowered beta-adrenergic responsiveness seen in
      hypothyroidism could be mimicked by agents acting at the levels of
      phosphodiesterase (enprofylline), adenylate cyclase (forskolin) and protein
      kinase (dibutyryl cAMP). In hyperthyroidism, the increased beta-adrenergic
      sensitivity and responsiveness were not seen when lipolysis was stimulated at the
      adenylate cyclase, phosphodiesterase, or protein kinase levels. There was no
      change in the numbers of adipocyte beta- and alpha 2-adrenoceptors in
      hypothyroidism. However, the number of beta-adrenergic binding sites was doubled,
      whereas the fraction and affinities of isoprenaline high affinity sites remained
      unchanged in hyperthyroidism. Thus, the influence of thyroid hormone on
      catecholamine-stimulated lipolysis in man acts through different mechanisms when
      adipocytes are exposed to high or low levels of thyroid hormones. In
      hyperthyroidism, lipolysis adapts to increasing energy demands through an
      increase in the beta-adrenoceptor number and, thus, a more effective coupling of
      the adenylate-cyclase complex. In hypothyroidism, the low lipolytic effect of
      catecholamines seems to be mainly due to an impairment at the protein kinase
      level or to the hormone-sensitive lipase itself.

PMID- 8157719
TI  - Magnetic resonance imaging evaluation of adipose tissue and muscle tissue mass in
      children with growth hormone (GH) deficiency, Turner's syndrome, and intrauterine
      growth retardation during the first year of treatment with GH.
AB  - Measurement of muscle and fat tissue mass by magnetic resonance imaging of the
      thighs was used to study the metabolic effect of human (h) GH in 23 GH
      deficiency, 8 Turner's syndrome, and 14 intrauterine growth retardation
      prepubertal patients. They were evaluated before and 1, 3, 6, and 12 months after
      the onset of hGH treatment. Seven normal children were followed longitudinally as
      controls. During hGH treatment, a significant increase in muscle tissue and
      decrease in adipose tissue cross-sectional areas was observed, leading to a
      dramatic increase in the muscle/adipose tissue cross-sectional area ratio in each
      period studied. These findings remained highly significant when corrected for the
      small variation observed in controls. The body mass index was correlated with
      muscle and adipose tissue cross-sectional area at each time point (P < 0.0001).
      The muscle cross-sectional area increment correlated with the first year height
      velocity (P < 0.01). This study indicates that in children with and without GH
      deficiency, hGH therapy induces rapid and intense variation of muscle and adipose
      tissue mass, and that magnetic resonance imaging can be used to study some
      aspects of the metabolic actions of GH.

PMID- 8157720
TI  - Dietary restriction reduces luteinizing hormone (LH) pulse frequency during
      waking hours and increases LH pulse amplitude during sleep in young menstruating
      women.
AB  - To determine the effect of dietary energy restriction on gonadotropins, we
      assayed LH and FSH in samples drawn at 10- and 60-min intervals, respectively,
      over 24 h from seven young women (mean +/- SE gynecological age, 7.7 +/- 1.2 yr)
      on day 9, 10, or 11 of two menstrual cycles. Cortisol was measured in samples
      collected at 30-min intervals. During the 4 previous days and the day of
      sampling, dietary energy intake was set at either 45 or 10 Cal/kg lean body
      mass.day in random order. Beginning 2 days before treatment, blood was sampled
      daily at 0800 h and assayed for T3, insulin-like growth factor-I, and insulin.
      Estradiol was measured in samples collected daily and at 6-h intervals on the day
      of frequent sampling. By the day of frequent sampling, dietary restriction had
      reduced T3 20% (P < 0.01), insulin-like growth factor-I 58% (P < 0.001), and
      insulin 54% (P < 0.001). Twenty-four-hour transverse means for LH (P = 0.3), FSH
      (P = 0.2), estradiol (P = 0.3), and cortisol (P = 0.13) were unaffected, but LH
      pulse frequency was reduced 23% (P < 0.01), especially during waking hours,
      whereas LH pulse amplitude was increased 40% (P = 0.05), especially during sleep.
      These results support the hypothesis that LH pulsatility depends upon energy
      availability in women, as it does in other mammalian species.

PMID- 8157721
TI  - Luteinizing hormone pulsatility in subjects with 5-alpha-reductase deficiency and
      decreased dihydrotestosterone production.
AB  - The pattern of LH pulsatility in male pseudohermaphrodites with inherited 5 alpha
      reductase-2 deficiency (5 alpha RD) and decreased levels of plasma
      dihydrotestosterone was compared to that in normal males. Analysis of 10-min
      plasma LH sampling during either a 10- or 24-h period demonstrated that the
      subjects with 5 alpha RD had 1) a mean plasma LH level, mean LH pulse amplitude,
      and mean plasma LH nadir that were approximately twice normal; and 2) a mean LH
      pulse frequency similar to that in normal males, whether described as pulses per
      h or pulses per study period. An increased plasma LH response to GnRH
      administration was also noted. The findings suggest that a deficiency of DHT
      results in decreased negative feedback at the level of the hypothalamus and/or
      pituitary, resulting in an increase in mean plasma LH, LH pulse amplitude, and LH
      responsiveness to GnRH. In response to increased LH, mean plasma testosterone
      (T), free T, and plasma estradiol (E2) are increased. The pulse amplitude is
      increased despite elevated plasma T and E2 levels; this underscores the
      importance of DHT in pulse amplitude regulation. LH pulse frequency is not
      decreased despite elevated plasma T and E2, raising the possibility that DHT
      deficiency increased pulse frequency that was normalized by increased T and/or
      E2. In conclusion, studies of LH pulsatility in subjects with 5 alpha RD suggest
      a role for DHT in the modulation of LH.

PMID- 8157722
TI  - Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma
      gene locus.
AB  - The retinoblastoma tumor suppressor gene (RB1) is inactivated in hereditary and
      sporadic forms of retinoblastoma as well as in a number of other sporadic tumors.
      The majority of human pituitary tumors have been shown to be monoclonal
      neoplasms, suggesting that 1 or more somatic mutations are involved in the clonal
      expansion of a single progenitor cell. Recently, a high percentage of transgenic
      mice containing a disrupted RB1 allele have been shown to develop pituitary
      tumors. To investigate whether RB1 inactivation contributes to the development of
      human pituitary adenomas, we searched for loss of heterozygosity (LOH) within the
      RB1 gene locus in a variety of human pituitary adenomas. We screened 34 adenomas
      for LOH using a polymerase chain reaction (PCR)-based microsatellite polymorphic
      marker at the RB1 gene locus. In addition, a variable number of tandem repeat
      markers from within the RB1 gene was also used to search for LOH in 14 tumors. We
      found no LOH or microsatellite instability at the RB1 locus in any of the
      informative cases (30 of 34). Additionally, we showed that 4 representative
      adenomas from female patients are monoclonal in origin using a PCR-based
      clonality analysis assay. We conclude that the RB1 gene shows no LOH in a variety
      of human pituitary adenomas and that PCR-based microsatellite markers can serve
      as a useful tool for LOH analysis in human pituitary tumors.

PMID- 8157723
TI  - Impaired renal 11 beta-oxidation of 9 alpha-fluorocortisol: an explanation for
      its mineralocorticoid potency.
AB  - 9 alpha-Fluorocortisol (9 alpha FF) is about 200 times more potent as a
      mineralocorticoid than cortisol (F) in man, although it binds with the same
      affinity as F and aldosterone to the human mineralocorticoid receptor. The low
      mineralocorticoid activity of F has been shown to be due to its rapid conversion
      by the kidney to cortisone (E), which does not bind to the receptor. Therefore,
      we compared the conversion of F to E with that of 9 alpha FF to 9 alpha
      fluorocortisone (9 alpha FE) by 11-hydroxysteroid dehydrogenases in man in vivo
      and in vitro. Single oral doses of 9 alpha FF, 9 alpha FE, and F were given to
      normal males, and the excretion of free 9 alpha FF, 9 alpha FE, F, and E was
      measured in urine. Human kidney and liver slices were incubated with unlabeled
      steroids, and the free 11-hydroxy- and 11-oxosteroids were quantitated after high
      performance liquid chromatography separation by UV absorption. Oral F (5 mg) is
      excreted 70% as free E and 30% as free F (percentage of free steroids only). Oral
      9 alpha FF (5 mg) is excreted 90% as free 9 alpha FF and 10% as free 9 alpha FE.
      Free 9 alpha FF excretion is 14 times greater than that of F after ingesting an
      identical dose. Oral 9 alpha FE (4 mg) is also excreted 90% as 9 alpha FF and 10%
      as 9 alpha FE. Kidney slices convert F much faster to E than 9 alpha FF to 9
      alpha FE. The conversion of 9 alpha FE to 9 alpha FF is, on the contrary, much
      faster than that of E to F. Thus, the equilibrium of the reaction is on the 11
      oxo side for F/E and on the 11-hydroxy side for 9 alpha FF/9 alpha FE. The
      interconversion of both pairs of steroids is inhibited by glycyrrhetinic acid in
      a dose-dependent manner. Liver slices do not measurably convert 9 alpha FF to 9
      alpha FE, but do rapidly convert 9 alpha FE into 9 alpha FF. Reflecting this
      negligible conversion of 9 alpha FF to 9 alpha FE and the low plasma-protein
      binding of 9 alpha FF, free urinary 9 alpha FF excretion is much higher than that
      of F after the same oral dose.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8157724
TI  - Interaction of human chorionic gonadotropin (hCG) and asialo-hCG with recombinant
      human thyrotropin receptor.
AB  - hCG is a putative thyroid stimulator. The present studies were undertaken to
      examine its interaction and that of its desialylated variant asialo-hCG with
      recombinant human TSH (hTSH) receptor (hTSHr). To this end, we transfected a
      human thyroid carcinoma cell line (HTC) lacking endogenous TSHr with the full
      length cDNA of the hTSHr. Unlike the wild type, the transfected cells, termed HTC
      TSHr cells, were able to bind bovine TSH (bTSH) with high affinity and increase
      cAMP production in response to bTSH stimulation. Of the hCG forms, intact hCG
      displayed a weak activity to inhibit [125I] bTSH binding to HTC-TSHr cells, with
      100 mg/L (2.6 x 10(-6) mol/L) producing maximally a 20% inhibition, whereas
      asialo-hCG achieved half-maximum binding inhibition at a concentration of 8 mg/L
      (2.3 x 10(-7) mol/L). The inhibitory constant (Ki) of asialo-hCG for recombinant
      hTSHr was calculated from saturation experiments in the presence of variable
      doses of bTSH and a fixed concentration of asialo-hCG to be approximately 8 x 10(
      8) mol/L. The interaction of asialo-hCG with TSHr was further assessed by studies
      of the direct binding of the radioactively labeled hormone to both HTC and HTC
      TSHr cells. [125I]Asialo-hCG binding to HTC-TSHr cells was 4.7%, compared to 1.5%
      in the wild-type cells lacking TSHr and was displaceable by bTSH (0.1-100 IU/L),
      indicating specific binding of the tracer to TSHr. Functionally, hCG (up to 100
      mg/L; 2.6 x 10(-6) mol/L) proved unable to evoke any significant cAMP response
      over basal values in HTC-TSHr cells, as did asialo-hCG. Asialo-hCG, but not hCG,
      inhibited bTSH-stimulated adenylate cyclase activity in the cells in a dose
      dependent manner. In conclusion, the present data show that intact hCG binds only
      weakly to HTC-TSHr cells and produces no significant cAMP stimulation, which is
      at variance with data obtained in FRTL-5 and Chinese hamster ovary-TSHr cells,
      but in good accord with previous findings in human thyroid membranes. Asialo-hCG,
      on the other hand, strongly binds to recombinant TSHr and inhibits the cAMP
      response to bTSH in HTC-TSHr cells, indicating that the desialylated hCG variant
      directly interacts with the receptor and truly is an antagonist of the hTSHr.

PMID- 8157725
TI  - Effects of estrogen on response to edetic acid infusion in postmenopausal
      osteoporotic women.
AB  - We and others have hypothesized that estrogen helps preserve bone mass by
      affecting the PTH/vitamin D regulation of skeletal metabolism. To evaluate this
      theory, we tested the effect of estrogen administration on parathyroid
      sensitivity to hypocalcemic challenge. Subjects were postmenopausal osteoporotic
      women recruited from a tertiary care clinic (9 untreated and 12 receiving hormone
      replacement therapy at the time of the investigation). After baseline serum and
      urine testing, edetic acid (50 mg/kg) was infused over a 2-h period. Serum and
      urine samples were obtained over 5 h and 24 h after beginning the infusion. Serum
      ionized calcium dropped equally in both groups of women. There were overall group
      differences in PTH-(1-84) secretion (P < 0.02), with a greater peak (P < 0.04)
      and a longer period of elevation (P < 0.01) in the untreated than in the hormone
      treated osteoporotic women. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] and
      phosphorus as well as urinary phosphate and cAMP responded similarly in the two
      groups of women. Estrogenized osteoporotic women demonstrate a smaller PTH
      increment to hypocalcemia, indicating that the parathyroid has reduced
      sensitivity under the influence of estrogen. Despite the smaller PTH increase in
      estrogenized individuals, renal responses to PTH were the same as those in
      untreated osteoporotic women, implying an estrogen-mediated increase in the
      sensitivity of the kidney to PTH.

PMID- 8157726
TI  - Identification of estrogen receptor in human adipose tissue and adipocytes.
AB  - Estrogen has various effects on adipose tissue. Although the presence of estrogen
      receptor (ER) has been demonstrated in rat adipose tissue and adipocytes, ER has
      not been identified in human adipose tissue. In this study, we demonstrated the
      existence of ER protein and ER messenger RNA (mRNA) in human sc adipose tissue
      and adipocytes. The cytosol fraction of human adipose tissue was partially
      purified by ammonium sulfate precipitation, and the presence of ER protein was
      analyzed by [3H]estradiol (E2) binding assay and Western blot analysis. [3H]E2
      binding assay showed a low specific binding due to high nonspecific binding, and
      the dissociation constant (Kd) and maximal binding sites could not be obtained by
      Scatchard analysis. Western blots, however, showed the presence of ER protein in
      both the partially purified cytosol and nuclear fractions of human adipose
      tissue. The mol wt of ER in both fractions was approximately 66,000. Furthermore,
      Northern blot analysis of total RNA samples isolated from human adipose tissue
      showed the expression of ER mRNA at 6.2 kilobase in size. ER mRNA was also
      identified in isolated human adipocytes by the reverse transcription and
      polymerase chain reaction. These results indicated that both ER protein and ER
      mRNA are expressed in human adipocytes, suggesting that the effect of estrogen on
      human adipose tissues might involve a direct action.

PMID- 8157727
TI  - Markers of bone turnover in hyperthyroidism and the effects of treatment.
AB  - Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting
      bone formation, and urinary pyridinoline cross-link (Pyr) excretion, reflecting
      bone resorption, have been measured in 27 patients with hyperthyroidism and 30
      age-matched controls using direct and novel immunoassays. Hyperthyroid patients
      had higher (P < 0.001) levels of all 3 markers compared with control values: Pyr,
      246 +/- 181 nmol/mmol creatinine vs. 40 +/- 12 (+515%); OC, 55 +/- 23 vs. 23 +/-
      7.4 micrograms/L (+139%); and B-ALP, 22 +/- 17 vs. 10.0 +/- 5.0 micrograms/L
      (+120%). OC and Pyr levels were elevated above the normal range in most patients
      and were significantly correlated with serum free T3 concentrations (r = 0.53; P
      < 0.01 and r = 0.76; P < 0.001; for OC and Pyr, respectively). B-ALP levels were
      elevated in 11 of the 27 patients and did not correlate with serum thyroid
      hormone concentrations. After therapy for hyperthyroidism, Pyr and OC levels
      returned to normal within 1 month, whereas B-ALP transiently increased after 1
      month before falling to baseline levels. The relapse of hyperthyroidism observed
      in 1 patient was associated with a steep increase in bone markers. These results
      indicate that Pyr, measured using a new and convenient immunoassay, is a highly
      sensitive marker for altered bone metabolism in hyperthyroidism. The increases in
      OC and B-ALP were less impressive, suggesting an imbalance between resorption and
      formation with subsequent rapid bone loss in untreated hyperthyroidism. OC and B
      ALP also appear to reflect different aspects of osteoblast metabolism during the
      treatment of hyperthyroid patients.

PMID- 8157728
TI  - Bone histomorphometric changes after cyclic therapy with phosphate and etidronate
      disodium in women with postmenopausal osteoporosis.
AB  - The purpose of this study was to examine bone histomorphometry before and after 2
      yr of a double blind trial of etidronate to determine whether etidronate was
      associated with the development of osteomalacia and to clarify the mechanism of
      action. Sixty-eight postmenopausal women with vertebral compression fractures
      from 3 clinical centers received 1 g phosphate or placebo twice daily on days 1
      3, 400 mg etidronate or placebo daily on days 4-17, and 0.5 g calcium daily on
      days 18-91. This cycle was given eight times. Iliac crest bone was biopsied after
      tetracycline labeling. None of the patients developed osteomalacia. The
      placebo/placebo group lost significantly more bone volume than the other groups.
      The change in mineralizing surface was significantly different among groups due
      to the decrease in the placebo/etidronate group. Within groups, placebo/placebo
      showed a decrease in bone volume without other changes. Phosphate/placebo showed
      no changes. Placebo/etidronate showed decreases in osteoid volume, osteoid
      surface, mineralizing surface, bone formation rate, and activation frequency. The
      only change in phosphate/etidronate was a decrease in osteoid surface. We
      conclude that 2-yr treatment with cyclical etidronate does not cause osteomalacia
      and that the mechanism for the increased bone mass is probably a decreased
      activation frequency.

PMID- 8157729
TI  - Establishing a ketoconazole suppression test for verifying testosterone
      administration in the doping control of athletes.
AB  - The ratio of urinary testosterone (u-T) to epitestosterone (T/EpiT) is used to
      disclose testosterone (T) administration in the doping control of sports, and a
      ratio greater than 6 constitutes an offence. Nevertheless, the possibility of
      biological outliers must not be discounted, and the use of ketoconazole has been
      suggested for a dynamic test to distinguish between such athletes and those using
      T. In this investigation, ketoconazole was administrated to three groups of T
      pretreated and two groups of untreated healthy male subjects. The subjects in one
      of the pretreated groups were patients with mild hypogonadism. One untreated
      group consisted of athletes that had been tested three times with high urinary
      T/EpiT levels. The effects of ketoconazole administration on serum T (s-T) level
      and urinary T/EpiT ratio were monitored every 2 h for an 8-h period and clearly
      separated T-pretreated and untreated subjects into two clusters (P < 0.0001). The
      T/EpiT ratio increased and the s-T level remained unchanged in pretreated
      individuals during the ketoconazole test, whereas T/EpiT decreased by 60% and s-T
      by almost 90% in untreated subjects. The statistical power of the test increased
      by using several time points and combining the urinary T/EpiT with the s-T data.
      In conclusion, the ketoconazole test is suitable as a supportive dynamic test for
      the urinary T/EpiT ratio measurements in the doping control of athletes.

PMID- 8157730
TI  - Blood spot follicle-stimulating hormone during early postnatal life in normal
      girls and Turner's syndrome.
AB  - Although FSH has previously been found to be elevated during infancy in agonadal
      subjects, it is not known whether perinatal FSH levels are also increased.
      Neonatal blood spot FSH levels were studied retrospectively in nine full term
      girls born with Turner's syndrome and compared with presumably normal full term
      girls born the same week. FSH was measured using a highly specific
      immunoradiometric assay adapted to blood spots collected at the time of
      systematic neonatal screening. On day 5-6 after birth, FSH was undetectable (< 1
      IU/L) or low (1-4.4 IU/L) in normal girls. Among the nine patients with Turner's
      syndrome, five had FSH levels below 3 IU/L, and four showed slightly elevated
      levels, ranging from 4.3-10.9 IU/L. These differences in FSH secretion were not
      related to differences in karyotype. Among five patients studied longitudinally
      during the first 6 weeks of life, three showed increases in FSH levels to 14.9
      15.9 IU/L during the second week of life. However, this increase was comparable
      to that seen in some normal girls sampled on a second occasion during the first
      weeks after birth. One patient with Turner's syndrome still had low FSH (2.5
      IU/L) on day 23, but showed some increase to 8.5 IU/L on day 30. We conclude that
      1) in Turner patients, perinatal changes in FSH secretion are similar to those in
      normal girls, although there is already a lack of feedback control by gonadal
      hormones on the hypothalamo-pituitary axis; and 2) the FSH assay cannot be used
      for neonatal screening of Turner's syndrome.

PMID- 8157731
TI  - Immunohistochemical localization, messenger ribonucleic acid abundance, and
      activity of 15-hydroxyprostaglandin dehydrogenase in placenta and fetal membranes
      during term and preterm labor.
AB  - Type 1 15-hydroxyprostaglandin dehydrogenase (PGDH) is the main enzyme
      responsible for the metabolism of prostaglandin E2 (PGE2) and PGF2 alpha. To
      examine the possibility that a deficiency of PGDH might contribute to preterm
      labor, we measured localization of immunoreactive (IR-) PGDH, PGDH mRNA, and PGDH
      enzyme activity in chorio-decidua, placenta, and amnion in patients after term
      elective cesarean section (n = 9), after spontaneous vaginal term delivery (n =
      10), and at idiopathic preterm labor (PTL) in the absence of infection (< 36
      weeks gestation; n = 11). Localization of IR-PGDH was determined in additional
      specimens of membranes after PTL with infection (n = 13) and without (n = 37). IR
      PGDH was localized in syncytiotrophoblast and intermediate trophoblasts in
      placenta and in the trophoblast layer of extraplacental chorion, but was absent
      from amnion in all patient groups. In chorion, the number of IR-positive
      trophoblasts was significantly reduced in the idiopathic PTL group compared to
      those in the other groups. The relative abundance of PGDH mRNA in the chorio
      decidua, but not the placenta, from spontaneous labor and PTL was significantly
      less than that after cesarean section. PGDH mRNA in chorio-decidua from preterm
      patients correlated with PGDH enzyme activity. Undetectable or low IR-PGDH in
      chorionic trophoblasts was also associated with low enzyme activity. These
      results suggest that there exists a subset of patients that present in PTL
      because of reduced PGDH expression in chorionic trophoblasts. We suggest that
      this relative deficiency would allow PGs synthesized in the amnion or chorion to
      escape metabolism in the chorion and thereby contribute to the stimulus to
      idiopathic PTL.

PMID- 8157732
TI  - Nomenclature of thyroid hormone receptor beta-gene mutations in resistance to
      thyroid hormone: consensus statement from the first workshop on thyroid hormone
      resistance, July 10-11, 1993, Cambridge, United Kingdom.

PMID- 8157733
TI  - Increased chemiluminescence response of neutrophils from the peripheral blood of
      patients with senile dementia of the Alzheimer's type.
AB  - The metabolic activity of circulating neutrophils from patients with senile
      dementia of the Alzheimer's type (SDAT) was investigated by a chemiluminescence
      assay and compared with that of old and young healthy controls. Neutrophils from
      demented patients showed a higher and faster chemiluminescence emission than
      those of controls when activated in vitro by autologous or heterologous sera.
      Granulocytes from patients with Parkinson's disease did not show an increased
      chemiluminescence activity. Moreover, serum from patients with SDAT depressed the
      chemiluminescence emission of granulocytes from young donors. Serum levels of
      alpha 1-antichymotrypsin (alpha 1-ACT) were also determined and were found to be
      higher in demented subjects than in old and young controls. These data suggest
      that peripheral and systemic indexes of inflammation are present in the disease
      and might be associated with mental deterioration.

PMID- 8157734
TI  - Morphological changes in oligodendrocytes in the intact mouse optic nerve
      following intravitreal injection of tumour necrosis factor.
AB  - Intracellular dye-injection was used to determine the whole-cell morphology of
      oligodendrocytes in intact optic nerves of mice following intravitreal injection
      of tumour necrosis factor-alpha (TNF alpha) or heat-inactivated TNF alpha to act
      as controls. Oligodendrocytes in control nerves had a stereotypic morphology, and
      provided an average of 20 axons with single internodal myelin segments of around
      200 microns internodal length. Oligodendrocytes with abnormal morphological
      features were identified 8-14 days following intravitreal injection of TNF alpha.
      Internodal myelin segments developed swellings along their lengths, became
      attenuated, and in extreme cases receded completely. This study provides a new
      insight into the process of demyelination, especially of the early stages which
      are not amenable with other techniques. Furthermore, it confirms that injection
      of TNF alpha into the vitreous, a fluid compartment of the CNS, instigates a
      sequence of events which results in oligodendrocyte disruption and demyelination.
      The mechanism by which intravitreally injected TNF alpha mediates these changes
      in optic nerve oligodendrocytes are yet unknown.

PMID- 8157735
TI  - Characterization of a murine central nervous system-derived cell line:
      infectability and presentation of viral antigen.
AB  - The cerebral endothelial cell line, 33-Mse, was characterized for its MHC antigen
      expression, infectability with viruses and capacity to present antigen to immune
      spleen cells. The cell line had interferon-gamma inducible MHC antigen
      expression. Infection by Theiler's murine encephalomyelitis influenced the
      expression of MHC molecules on the cell surface of this line. These cells could
      not stimulate T splenocyte proliferation or act as targets for Theiler's murine
      encephalomyelitis cytolytic immune spleen cells. These cells were able to present
      viral antigen to vaccinia virus immune spleen cells and act as targets for
      cytotoxic T cells from vaccinia virus immune mice.

PMID- 8157736
TI  - Neuropeptide Y is an inducible gene in the human immune system.
AB  - This study reports on neuropeptide Y (NPY) mRNA expression in human peripheral
      blood mononuclear cells (PBMC) and lymphoid tissues. By reverse transcription
      polymerase chain reaction (RT-PCR) it is shown that activated human PBMC of
      normal blood donors expressed the NPY gene. The PCR products had the expected
      size and Northern blotting demonstrated the presence of the 0.8-kb NPY mRNA. To
      define the subpopulations of mononuclear cells expressing this neuropeptide,
      purified monocytes, B cells and T cells were stimulated with specific activators.
      Monocytes and in vitro matured macrophages expressed NPY mRNA in response to
      phorbol myristate acetate (PMA). B lymphocytes expressed NPY mRNA following
      stimulation with antibody to surface immunoglobulin and PMA. In order to analyze
      whether these cell types express NPY under physiological conditions in vivo,
      human bone marrow, tonsil and thymus were analyzed. In situ hybridization of bone
      marrow revealed a small number of cells containing high levels of NPY mRNA which
      was also detected in RNA extracts of human thymus and tonsil. In summary, NPY is
      an inducible gene in human lymphocytes and monocytes and it is expressed at sites
      where these cells are activated in vivo.

PMID- 8157737
TI  - Anti-acetylcholine receptor (AChR) antibodies measurement in myasthenia gravis:
      the use of cell line TE671 as a source of AChR antigen.
AB  - Acetylcholine receptor (AChR) from the human rhabdomyosarcoma cell line TE671 was
      compared with that of human ischaemic muscle AChR as a source of the antigen for
      the diagnosis of myasthenia gravis (MG). The sera, which were anti-TE671 cell
      AChR antibody-negative, all came from patients with low anti-human muscle AChR
      antibody titers. None of the sera that were seronegative as a result of the human
      muscle AChR RIA became positive with TE671 cell AChR. The overall sensitivity was
      7% less using TE671 cell AChR. The lower sensitivity was observed irrespective of
      the clinical form of MG. It also appeared from this study that epitopes specific
      to the junctional isoform of human AChR are essential for the detection of low
      antibody titers, which accounts for this feature, since TE671 cells only express
      the extrajunctional isoform of AChR in the surface membrane. Accordingly, AChR
      from cell line TE671 cannot replace human muscle AChR in the conventional
      diagnostic immunoprecipitation RIA. There are, however, many other useful
      implications of AChR from cell line TE671.

PMID- 8157738
TI  - Tumor necrosis factor polymorphism in multiple sclerosis: no additional
      association independent of HLA.
AB  - In order to investigate whether genes coding for tumor necrosis factors (TNF)
      contribute to the pathogenesis of multiple sclerosis (MS) and also whether they
      have a non-random association with the MS associated HLA-DRB1*1501-DQA1*0102
      DQB1*0602 haplotype, 40 MS patients and their parents were characterized at four
      polymorphic loci in the region of the TNF genes: a NcoI RFLP and three
      microsatellites. We were able to determine the parental haplotypes and used those
      which were not transmitted to the proband as controls. Fifty percent of the HLA
      DRB1*1501-DQA1*0102-DQB1*0602 haplotypes carried the TNFc1-n2-a11-b4 allelic
      combination in both the patient and the control groups. However, there was no
      association of any of these TNF polymorphisms with MS, independent of that
      already described for the class II region. This, with the lack of association of
      DP alleles with MS, effectively marks the boundaries of the MS associated
      haplotype.

PMID- 8157739
TI  - New technology in hospital blood banking.

PMID- 8157740
TI  - ACP Broadsheet No 140: July 1993. Techniques in pulmonary cytopathology.

PMID- 8157741
TI  - Early clinical pathologists: Robert Koch (1843-1910).

PMID- 8157742
TI  - Can histopathologists reliably diagnose molar pregnancy?
AB  - AIMS: To assess the degree of difficulty in diagnosing partial mole by analysing
      intraobserver and interobserver agreement among a group of pathologists for these
      diagnoses. METHODS: Fifty mixed cases of partial mole, complete mole, and non
      molar pregnancy were submitted to seven histopathologists, two of whom are expert
      gynaecological pathologists; the other five were district general hospital
      consultants, one of whom works in Australia. These participants gave each slide a
      firm diagnosis of either partial mole, complete mole, or non-molar pregnancy.
      Some 12 months later, the slides were recorded and again submitted for a second
      diagnostic round to assess intraobserver as well as interobserver agreement.
      Standard histological criteria for each diagnostic category were circulated with
      the slides. RESULTS: kappa statistics showed that complete mole could be reliably
      distinguished from non-molar pregnancy, but neither non-molar pregnancy nor
      complete mole could be easily differentiated from partial mole. In only 35 out of
      50 cases was there agreement between five or more of the seven participants.
      Agreement between the expert gynaecological pathologists was no better than for
      others in the group. Interestingly, the intraobserver agreement for each
      pathologist was good to excellent. CONCLUSIONS: These results imply that the
      reported histological criteria are either not being applied consistently or that
      they are lacking in practical use. An atypical growth pattern of trophoblast,
      rather than the polar accentuation seen in normal first trimester pregnancies,
      seems to be the important diagnostic histological feature for partial mole.
      Ploidy studies might also help with problem cases.

PMID- 8157743
TI  - Histopathological changes in venous grafts and in varicose and non-varicose
      veins.
AB  - AIMS: To examine veins histologically from different sites in the body to study
      the effect of venous pressure; and to examine veins used as aortocoronary grafts.
      METHODS: The axillary vein, femoral vein at the inguinal ligament, the short
      saphenous vein at the knee and the long saphenous vein at the ankle were removed
      from 24 necropsy cases of patients aged 2 months to 80 years. Fifteen varicose
      saphenous veins and 12 aortocoronary grafts removed at surgery were obtained. All
      were examined histologically. RESULTS: Varying degrees of intimal thickening
      composed of collagen, elastin, and smooth muscle were found. These changes were
      most noticeable in the varicose veins. Intimal changes were also seen related to
      valves and to adjacent arteries. No clinically relevant lipid was seen in the
      native veins, though atheromatous changes were seen in the grafts. CONCLUSIONS:
      Venous changes are related to venous pressure, to local haemodynamic effects, and
      probably to hypoxia. The changes are often focal and seem to be sequential in
      their formation. True atheroma is seen in the aortocoronary grafts but is not
      seen in native veins and this may be the result of additional factors.

PMID- 8157744
TI  - Immunoglobulin and complement deposition in glomeruli of 756 subjects who had
      committed suicide or met with a violent death.
AB  - AIMS: To study immune deposits in renal glomeruli. METHODS: Tissue was obtained
      from 756 necropsy cases from people who had committed suicide or met with a
      violent death. Glomerular immune deposits were examined by immunofluorescence
      microscopy and a light microscopy. The clinical histories of all the decreased
      were studied to ascertain reasons for the deposits. RESULTS: Immune deposits were
      found in glomeruli in 91 (12%) cases. In 52 (6.8%) cases mesangial IgA was
      observed as a solitary finding in 34 (4.5%), and was accompanied by other
      immunoglobulins in 18 (2.4%). Mesangial IgM was present in 19 (2.5%) and IgG in
      11 cases (1.5%). Two cases had capillary IgG (0.3%). Light microscopic
      examination showed mesangial enlargement in eight of the cases with mesangial
      IgA. These included one with IgA glomerulonephritis diagnosed before death. Two
      cases with normal glomerular morphology and mesangial IgA deposits had clinical
      laboratory evidence of renal disease. In two subjects with normal glomerular
      morphology, mesangial IgM and microscopic haematuria were present. In one case
      with capillary IgG membranous glomerulonephritis was detected. CONCLUSIONS: Ten
      cases had mesangial IgA together with morphological or clinical laboratory
      findings suggestive of renal disease. If all these are regarded as IgA
      glomerulonephritis, then its prevalence can be estimated at 1.3%. For IgM
      glomerulonephritis, a prevalence of 0.3% was deduced.

PMID- 8157745
TI  - Stromal cell populations in necropsy bone marrow sections from allogeneic marrow
      recipients and non-transplant patients.
AB  - AIMS: To compare the numbers of alkaline phosphatase positive reticulum cells (AL
      RC) and macrophages in bone marrow transplant (BMT) recipients with numbers in
      normal subjects and to look for correlations with clinical features. METHODS:
      Sections of femoral marrow were obtained at necropsy from 18 BMT recipients and
      nine normal subjects who had died suddenly. AL-RC were visualised through their
      endogenous alkaline phosphatase activity. Macrophages were stained by an
      immunocytochemical technique using the antibody EBM/11 (CD68) and through their
      endogenous acid phosphatase activity. The numbers of stained cells were counted
      and expressed as a percentage of total nucleated cells. RESULTS: In both sets of
      marrow tissue, more macrophages stained for CD68 than for acid phosphatase,
      indicating macrophage heterogeneity. The percentage value for CD68 positive
      macrophages was higher among the transplant recipients (p < 0.01). At least in
      part this was caused by a reduction in haemopoietic cell numbers. Percentage
      values for acid phosphatase and alkaline phosphatase positive cells did not
      differ between the two groups. To exclude the effect of changes in marrow
      cellularity, stromal cell ratios were compared. The AL-RC: CD68 and acid
      phosphatase:CD68 ratios were both lower in BMT recipients, indicating that after
      BMT either the absolute number of AL-RC and acid phosphatase cells decreases, or
      CD68 cells increase, or there is a combination of the two. There was no
      correlation between the number of each cell type and cell dose given at
      transplantation, time after transplantation, presence of graft versus host
      disease or infection, marrow erythroid:myeloid ratio, or peripheral white cell
      count. The ratio of AL-RC to macrophages in our intact marrow was 0.43,
      considerably higher than that reported in cultured marrow. CONCLUSIONS: AL-RC and
      acid phosphatase positive cells may be most important for supporting haemopoiesis
      and their reduction after BMT may contribute to depression of haemopoiesis. CD68
      positive cells include macrophages with a wide variety of functions and these may
      be increased in response to marrow damage.

PMID- 8157746
TI  - Rapidly fatal necrotising fasciitis caused by Streptococcus pyogenes.
AB  - AIMS: To describe the morbid anatomical and bacteriological features in a series
      of five cases of rapidly fatal Streptococcus pyogenes necrotising fasciitis.
      METHODS: Post mortem and bacteriological examinations were made of five patients
      dying within 48 hours from rapidly fatal necrotising fasciitis. RESULTS: All five
      cases died rapidly from a toxic Streptococcus toxin syndrome as a result of
      developing necrotising fasciitis following trivial injury. CONCLUSIONS:
      Necrotising fasciitis caused by Streptococcus pyogenes infection can be rapidly
      fatal. This is probably the result of a toxic shock syndrome. Rapid, early
      diagnosis and swift and probably empirical treatment is required to avoid a fatal
      outcome.

PMID- 8157747
TI  - K-ras point mutations in routinely processed tissues: non-radioactive screening
      by single strand conformational polymorphism analysis.
AB  - AIMS: To develop a non-radioactive method to screen routinely fixed, paraffin wax
      embedded specimens for the occurrence of point mutations; to evaluate the single
      strand conformational polymorphism (SSCP) analysis technique for the detection of
      K-ras point mutations as a result of electrophoretic mobility shifts. METHODS:
      DNA was extracted from archival specimens of colon cancer and from established
      colon cancer cell lines with known point mutations. A K-ras gene fragment
      containing codons 12 and 13 of exon 1 was amplified with the polymerase chain
      reaction (PCR). Denatured DNA fragments were run on 10% polyacrylamide gels under
      non-denaturing conditions. After electrophoresis DNA was blotted and the single
      stranded DNA was detected using a digoxigenin labelled ras probe. The nature of
      the detected point mutations was identified and confirmed by sequencing and
      hybridisation with oligonucleotides using 32P labelling. RESULTS: Wild type and
      aberrant alleles were detected caused by mobility shifts after electrophoresis of
      the PCR products. Commonly occurring mutations in the K-ras gene--in the first
      two positions of codon 12--could easily be detected in DNA from archival paraffin
      wax embedded colon cancer tissue. In all the colon tumour samples studied wild
      type gene alleles were also found, presumably derived from normal cells in the
      specimen. CONCLUSIONS: The SSCP method permits rapid non-radioactive screening of
      adenomas or carcinomas for the occurrence of point mutations in the K-ras gene.
      But if a mutation is detected by an electrophoretic mobility shift, its
      identification requires confirmation by sequencing or oligonucleotide
      hybridisation.

PMID- 8157748
TI  - Sensitivity of PCR in detecting monoclonal B cell proliferations.
AB  - AIMS: To evaluate the rapid detection of various forms of monoclonal B cell
      proliferations by using the polymerase chain reaction (PCR) to identify clonal
      immunoglobulin heavy chain genomic rearrangements. METHODS: Thirty four B cell
      lymphomas defined by morphology, immunophenotyping, and positive immunoglobulin
      heavy chain gene rearrangements detected by Southern blot analysis were examined.
      An additional 22 cases representing miscellaneous lymphoproliferative and non
      lymphoproliferative disorders were also studied. RESULTS: Monoclonal
      rearrangements were identified in 19 (56%) cases of B cell lymphoma. The method
      was less sensitive in the detection of follicular centre cell lymphomas (15 of
      28, or 54%) than non-follicular centre cell lesions (four of six, or 67%).
      Monoclonal rearrangement was not identified in 19 control cases, including T cell
      lymphomas, Hodgkin's disease, reactive lymphadenopathy and metastatic carcinoma.
      Three cases showed positive immunoglobulin gene rearrangement by PCR but were
      negative on Southern blotting. Two of these cases had definite clinical,
      morphological, and immunophenotypic evidence of monoclonal B cell proliferation
      suggesting that PCR could, on occasion, pick up cases missed by Southern blotting
      and that the two methods are complementary in clonal lymphoproliferative disease
      diagnosis. The third case represented a "false positive" PCR reaction involving a
      colonic adenocarcinoma. CONCLUSIONS: PCR analysis, using the primer sequences
      outlined in this study, will detect about 55% of clonal lymphoproliferative
      proliferations with increased sensitivity for non-follicular centre cell lesions.
      With these levels of detection in mind, this testing strategy can still be
      especially useful in cases which prove diagnostically problematic with standard
      morphological and immunophenotypic analysis, and in instances where the quantity
      and type of diagnostic material is limiting (needle aspirates and cellular
      fluids).

PMID- 8157749
TI  - Toxoplasma infection and systemic lupus erythematosus: analysis of the
      serological response by immunoblotting.
AB  - AIMS: To examine the serological response of patients with systemic lupus
      erythematosus (SLE) and toxoplasma infection and to compare the blot profiles
      with those from immunocompetent subjects of similar immune response. METHODS:
      Forty serum samples from patients with SLE were tested for toxoplasma antibodies
      using the dye and indirect haemagglutination tests. Specific IgM was measured by
      mu-capture enzyme linked immunosorbent assay (ELISA). The sera were immunoblotted
      using antigen strips prepared from the RH strain of Toxoplasma gondii. For
      comparison, control blots were prepared from pooled sera from immunocompetent
      subjects with serological evidence of acute (pool 1), or chronic (pool 2)
      toxoplasma infection, or with no evidence of infection (pool 3). RESULTS: Some of
      the blot profiles from the patients with SLE were compatible with the
      corresponding serology but others showed considerable variation, particularly
      among the IgM blots. The blots from sera with low dye test titres suggested that
      the latter could be false positive results. CONCLUSIONS: Toxoplasma infection may
      enhance the production of autoantibodies which, when combined with the high
      titres characteristic of SLE, might interfere in the dye test and other
      serological tests. Immunoblotting could prove useful in the immunocompromised for
      confirming the presence of specific toxoplasma antibodies and for the staging of
      infection in those with positive serology.

PMID- 8157750
TI  - Detection of the C protein gene among group B streptococci using PCR.
AB  - AIM: To develop a polymerase chain reaction (PCR) for the specific detection of
      the C protein gene in strains of group B Streptococcus. METHODS: A single primer
      pair derived from the nucleotide sequence of the IgA binding beta antigen of the
      C protein complex permitted the specific amplification of a 592 base pair DNA
      fragment from the C protein gene. After 35 cycles of amplification this product
      could be detected by agarose gel electrophoresis. Southern blot hybridisation
      confirmed that this product was the C protein gene. RESULTS: PCR detected the C
      protein gene in 75 (63%) of 119 strains of group B streptococci analysed. The
      product was not detected in other Gram positive organisms, showing that this PCR
      assay was highly specific. The sensitivity of the assay was satisfactory to a
      dilution of 1 in 10,000 of extracted DNA. CONCLUSIONS: The C protein of group B
      streptococci is associated with neonatal sepsis. The specific detection of the C
      protein gene by PCR may help identify which strains are likely to be associated
      with infection by the organism.

PMID- 8157751
TI  - Multipoint identification of Enterobacteriaceae: report of the British Society
      for Microbial Technology collaborative study.
AB  - AIMS: To evaluate the accuracy and reproducibility of multipoint identification
      schemes in a multicentre trial. METHODS: Forty two strains of Enterobacteriaceae
      were distributed to 22 laboratories for identification by routine multipoint
      methods. Analysis of results enabled inter- and intralaboratory reproducibility
      of a variety of tests, and the ability of laboratories to identify individual
      organisms to be determined. RESULTS: Interlaboratory reproducibility of most of
      the biochemical tests was acceptable. The least reproducible tests, both within
      and between laboratories, were citrate utilisation, production of urease and beta
      galactosidase, detection of motility, and decarboxylation of lysine and
      ornithine. Inconsistent results for these tests were often associated with
      misidentified strains. Most laboratories performed identifications
      satisfactorily. Most isolates (72.1%) were identified correctly to species level;
      9.6% were incorrectly identified, and 6.4% could not be identified at all. The
      most difficult organisms to identify were Citrobacter freundii, Enterobacter
      cloacae, Hafnia alvei and Aeromonas hydrophila. Strains of Enterobacter, Serratia
      sp, and Providencia sp were difficult to speciate. Several laboratories could not
      identify organisms exhibiting at least one atypical biochemical reaction.
      CONCLUSION: This study emphasises the need for quality control of media and
      reagents for multipoint identification of Gram negative enteric bacilli.

PMID- 8157752
TI  - Phase contrast microscopic examination of urinary erythrocytes to localise source
      of bleeding: an overlooked technique?
AB  - AIMS: To localise the source of bleeding in the urinary tract in patients
      presenting with haematuria. METHODS: Urine samples were obtained from 109
      patients with symptoms referable to the urinary tract. The sample was examined
      for the presence of red blood cells by phase contrast microscopy (PCM) and the
      proportion of dysmorphic and isomorphic red blood cells was determined. If more
      than 20% of the red blood cells were dysmorphic a glomerular origin for the site
      of bleeding was suspected; if less than 20% of the red blood cells were
      isomorphic a non-glomerular origin was suspected. Phase contrast microscopy and
      clinical findings were correlated. RESULTS: The correct bleeding site was shown
      in 27 of 30 (90%) patients with glomerulopathy and in all 17 patients with
      bleeding from the lower urinary tract, indicating that this method of analysis
      has a sensitivity of 90% and specificity of 100% for detecting the glomerular
      source of bleeding. CONCLUSIONS: The examination of urine for dysmorphic and
      isomorphic red blood cells by phase contrast microscopy is strongly recommended
      in routine clinical practice for the detection of glomerular and non-glomerular
      lesions. This technique may avoid unnecessary investigations for the diagnosis of
      the site of bleeding in patients with haematuria.

PMID- 8157753
TI  - Detection of reactivation and size variation in the regulatory region of JC virus
      in brain tissue.
AB  - AIMS: To develop a sensitive and specific polymerase chain reaction (PCR) based
      system for detecting genomic variation in JC virus. To apply this system to
      formalin fixed, paraffin wax embedded brain tissue from patients with and without
      progressive multifocal leucoencephalopathy (PML). METHODS: A pair of primers (JC1
      and JC2) were designed to be complementary to the early and late regions of JC
      and BK polyomaviruses, respectively. A third primer (JC3), internal to JC1 and
      JC2, was designed to be specific for JC virus. The specificity of JC3 was
      investigated by amplifying plasmids with BK or JC virus genomes. Sensitivity was
      estimated by titration of a plasmid containing JC virus genome. Seven brains from
      patients with PML (PMLB) and 30 from patients without PML (non-PMLB) were
      amplified using JC1 and JC2, followed by JC1 and JC3. Amplification of the beta
      globin gene was used as an amplification control. RESULTS: Amplification with JC1
      and JC2 was common for JC and BK viruses, but with JC1 and JC3 it was specific
      for JC virus. The sensitivity of the system was 25 copies of JC plasmid per 10
      microliters of digested tissue. Five out of seven PMLB and 28 of the 30 non-PMLB
      amplified for beta globin, but only the PMLB gave a signal with polyoma primers.
      Hypervariation of the length of the regulatory region of the JC isolates in the
      PML tissues was consistent with the presence of multiple strains of JC.
      CONCLUSIONS: Variation in the regulatory region of JC virus can be specifically
      and sensitively detected from routinely processed, paraffin wax embedded brain
      tissue. Variation in the regulatory region is common in PML derived JC strains,
      but JC virus was not detectable in non-PMLB tissue.

PMID- 8157754
TI  - Vitreous humour and cerebrospinal fluid hypoxanthine concentration as a marker of
      pre-mortem hypoxia in SIDS.
AB  - AIMS: To assess the rate at which premortem hypoxia occurs in sudden infant death
      syndrome (SIDS) when compared with death in early childhood. METHODS: The
      hypoxanthine concentration was measured as a marker of premortem hypoxia in
      vitreous humour and cerebrospinal fluid samples obtained at necropsy from 119
      children whose ages ranged from 1 week to 2 years. RESULTS: Increasing interval
      between death and necropsy was accompanied by an increase in the hypoxanthine
      concentration of vitreous humour for the first 24 hours, at a rate of 8.3
      mumol/l/hour. Thereafter, there was little change with time, and the results wer
      corrected to 24 hours according to a regression equation. Cerebrospinal fluid
      concentrations showed no significant change with time following death. Patients
      were divided into three groups according to the cause of death: SIDS, cardiac or
      pulmonary disease, and others. Median values for the cerebrospinal fluid
      hypoxanthine concentrations were not significantly different among the groups and
      no difference could be shown between the vitreous humour hypoxanthine
      concentration in cases of SIDS and those children dying from other causes.
      Patients with established cardiac or pulmonary disease had a significantly
      reduced vitreous humour hypoxanthine concentration which may have reflected the
      premortem use of artificial ventilation. CONCLUSIONS: The results of this study
      do not support the view that pre-mortem hypoxia is a common feature in SIDS when
      compared with other causes of death.

PMID- 8157755
TI  - Plasma intestinal alkaline phosphatase isoenzymes in neonates with bowel
      necrosis.
AB  - AIM: To determine if the intestinal isoenzymes of alkaline phosphatase (ALP) are
      biochemical markers of bowel necrosis in neonates. METHODS: Plasma ALP isoenzymes
      were measured in 22 babies with bowel necrosis, histologically confirmed, and in
      22 matched controls. The isoenzymes were also measured in 16 infants with signs
      of necrotising enterocolitis, who recovered without histological confirmation of
      bowel necrosis. The isoenzymes were separated by polyacrylamide gel
      electrophoresis. Auxiliary tests for identification included neuraminidase
      digestion and treatment with monoclonal and polyclonal antiplacental antibodies.
      RESULTS: Intestinal ALP was detected in 16 infants with bowel necrosis--13 had
      fetal intestinal ALP (FI-ALP) and three had adult intestinal ALP (AI-ALP). FI-ALP
      was detected in nine of the controls. In the babies with bowel necrosis
      intestinal ALP was found over all gestations, but in the controls only in those
      less than 34 weeks. The percentages of total ALP activity due to intestinal ALP
      were significantly higher in those with bowel necrosis compared with matched
      controls (p = 0.028). In babies of all gestations diagnostic sensitivity for the
      presence of intestinal ALP as a marker of bowel necrosis was 73% and diagnostic
      specificity 59%. In babies greater than 34 weeks' gestation, diagnostic
      sensitivity fell to 60% but the test became completely specific. In two babies FI
      ALP increased from zero/trace to high activity coincident with the episode of
      bowel necrosis. In 16 babies with signs of necrotising enterocolitis but
      unconfirmed bowel necrosis FI-ALP was detected in four. CONCLUSION: Intestinal
      ALP seems to be released into the circulation in some babies with bowel necrosis,
      but its detection does not have the diagnostic sensitivity and specificity to be
      a reliable biochemical marker of the condition.

PMID- 8157756
TI  - Pharmacokinetics of sex steroids in patients with beta thalassaemia major.
AB  - AIMS: To assess the pharmacokinetics of oral, intramuscular, or transdermal
      hormone replacement in patients with beta thalassaemia major. METHODS: Oral
      (testosterone undecanoate 40 mg) and intramuscular (testosterone propionate 15
      mg, phenylpropionate 30 mg, isocaproate 30 mg and decanoate 50 mg) testosterone
      and transdermal (17 beta oestradiol 25 micrograms and 50 micrograms) oestradiol
      were evaluated in 21 male (16-29 years) and 11 female (19-26 years) patients with
      beta thalassaemia major and various forms of hypogonadism. RESULTS: In male
      patients given oral testosterone, peak testosterone concentrations were observed
      either two to four hours or seven hours after administration; intramuscular
      testosterone produced peak values seven days after injection. Transdermal 17 beta
      oestradiol given to female patients produced a biphasic pattern with an initial
      peak concentration occurring at 36 hours and a secondary rise at 84 hours.
      CONCLUSIONS: The results indicate that oral androgens should be given twice daily
      in cases of hypogonadism, and where growth is incomplete, lower than recommended
      doses. If intramuscular testosterone is used, smaller doses of 10-25 mg should be
      given every one to two weeks. Transdermal administration of 25-50 micrograms 17
      beta oestradiol generally produces a plasma E2 value in the early to mid
      follicular phase range (100-300 pmol/l). This is appropriate in adults but
      excessive for prepubertal girls. Diffuse iron infiltration of tissues does not
      seem to interfere with the absorption of androgens and oestrogens from the gut,
      muscle, or skin.

PMID- 8157757
TI  - Lupus anticoagulant activity of some antiphospholipid antibodies against
      phospholipid bound beta 2 glycoprotein I.
AB  - AIMS: To determine whether beta 2 glycoprotein I (beta 2GPI) dependent
      anticardiolipin (aCL) antibodies detected in solid phase enzyme linked
      immunosorbent assays can also have lupus anticoagulant activity. METHODS: Six
      anticardiolipin antibodies were affinity purified from patients with these
      antibodies and lupus anticoagulant activity in their plasma. RESULTS: The
      anticardiolipin antibodies bound only to anionic phospholipids in the presence of
      beta 2GPI and bound to beta 2GPI in the absence of phospholipids. Four out of six
      had lupus anticoagulant activity in the dilute Russell viper venom time test.
      CONCLUSIONS: The results show that some beta 2GPI dependent aCL are lupus
      anticoagulants. It is unclear why only some should have lupus anticoagulant
      activity while others do not.

PMID- 8157758
TI  - Immunophenotypic characterisation of acute leukaemia after polycythemia vera.
AB  - AIMS: To analyze the immunophenotype of blast cells in patients with acute
      leukaemia after polycythemia vera, together with the most relevant clinical and
      haematological disease characteristics. METHODS: The immunophenotype was analysed
      in nine patients by immunofluorescence flow cytometry using a panel of 15
      monoclonal antibodies. The DNA content of blast cells was determined using
      Vindelov's technique. RESULTS: The most relevant clinical and haematological
      disease characteristics included: the presence of enlarged spleen and liver by
      56% and 67%, respectively; a moderate degree of leucocytosis with
      thrombocytopenia while haemoglobin was normal in 50% of patients. All patients
      received alkylating agents or hydroxyurea, or both. Interestingly, the chronic
      phase in patients receiving this latter drug was shorter. All cases showed a
      myeloid phenotype, four of them reactive only to early myeloid antigens
      (CD13/33); in the remaining cases the blast cells displayed granulomonocytic
      (CD14+, CD15+), erythroid (CD71 ), or megakaryocytic (CD61+, CD41+) markers.
      Coexpression of lymphoid related antigens (CD7, TdT, or CD19) was also detected.
      The morphological assessment of blast cells agreed with the immunophenotyping in
      five out of the nine cases. Blast cells from all six patients analysed displayed
      a diploid DNA content and the proportion of S-phase cells ranged from 0.4% to 4%.
      CONCLUSIONS: These findings suggest a pluripotential stem cell with myeloid
      commitment as the target cell of acute leukaemia after polycythemia vera.

PMID- 8157760
TI  - Pericardial extramedullary haemopoiesis in chronic myelomonocytic leukaemia.
AB  - Chronic myelomonocytic leukaemia (CMML) is a myelodysplastic syndrome with a
      diverse clinical spectrum. A case of a 60 year old man with CMML who developed
      cardiac tamponade is reported. Cytological examination of the pericardial
      effusion fluid showed extramedullary haemopoiesis. Serous effusions are well
      recognised in association with this disease, but this seems to be the first
      reported case of extramedullary haemopoiesis resulting in a pericardial effusion
      in a patient with CMML.

PMID- 8157759
TI  - Eosinophilic leukaemia with trisomy 8 and double gammopathy.
AB  - Prolonged eosinophilia of unknown cause has generally been described as the
      hypereosinophilic syndrome, and is characterised by peripheral blood and bone
      marrow infiltration and frequent multisystem disease. The nature of this disorder
      has been questioned, and the clinical features are quite variable, suggesting its
      heterogeneity and probable neoplastic aetiology. A patient with severe
      eosinophilia, karyotype abnormalities, serum gammopathy and massive organ disease
      is reported. The clinical course was aggressive despite cytoreduction of
      eosinophils and terminated in multisystem failure. These findings are consistent
      with a diagnosis of eosinophilic leukaemia, and it is suggested that chromosome
      and cell culture studies might be useful in the early diagnosis of this
      controversial entity.

PMID- 8157761
TI  - p53 expression in three separate tumours from a patient with Li-Fraumeni's
      syndrome.
AB  - The Li-Fraumeni cancer syndrome is a rare autosomal dominant syndrome,
      characterised by the occurrence of diverse mesenchymal and epithelial neoplasms
      at multiple sites. It has recently been shown that some of these individuals have
      a germ line mutation of the p53 tumour suppressor gene. The case of one member of
      such a family who has now developed three separate primary malignant tumours is
      reported. All three tumours expressed mutant p53 protein.

PMID- 8157762
TI  - Waldenstrom's macroglobulinaemia secreting a paraprotein with lupus anticoagulant
      activity: possible association with gastrointestinal tract disease and
      malabsorption.
AB  - A 51 year old man with Waldenstrom's macroglobulinaemia presented with a
      malabsorptive syndrome related to extensive small bowel lymphangiectasia caused
      by immunoglobulin accumulation. The patient's plasma had strong lupus
      anticoagulant activity and the IgM lambda paraprotein displayed specificity for
      the negatively charged phospholipids phosphatidyl serine and phosphatidyl
      inositol, as well as the neutral phosphatidic acid. Despite treatment for the
      macroglobulinaemia the patient died and at necropsy was found to have myocardial
      ischaemia and segmental infarcts in the spleen and kidney. The coexistence of
      these relatively rare findings suggests a possible association between
      Waldenstrom's macroglobulinaemia with gastrointestinal manifestations and
      paraprotein specificity for phospholipid.

PMID- 8157763
TI  - Terminal subculture of blood cultures using a multipoint inoculator device.
AB  - A multipoint inoculation method was used for the terminal subculture of blood
      cultures. This economical yet reliable technique successfully isolated important
      human pathogens such as Haemophilus influenzae from macroscopically negative
      blood cultures.

PMID- 8157764
TI  - Expression of parathyroid hormone related peptide in human pituitary tumours.
AB  - The presence of parathyroid hormone related peptide (PTHrP) was studied in 20
      patients with pituitary adenomas and one patient with pituitary adenocarcinoma.
      PTHrP expression was shown in almost all of the pituitary adenomas (95%) and in
      100% (n = 7) growth hormone producing pituitary adenomas. A metastatic lesion
      from a pituitary growth hormone producing adenocarcinoma revealed strongly
      expressed PTHrP. It was weakly detected in normal pituitary cells in all of the
      specimens (n = 10). There was no significant correlation, however, between PTHrP
      expression and the clinical or pathological features of growth hormone producing
      tumours. Apart from an important role in the physiological function of the
      pituitary gland, PTHrP may be closely related to somatotroph tumorigenicity.

PMID- 8157765
TI  - Histology compared with chemical testing for urease for rapid detection of
      Helicobacter pylori in gastric biopsy specimens.
AB  - Gastric biopsy specimens from 283 patients with ulcer and non-ulcer dyspepsia
      attending five gastroenterology clinics in the northern region of the United Arab
      Emirates (UAE) were tested by the agar gel test (n = 115) or the ultra-rapid
      endoscopy room test (n = 168) for the presence of Helicobacter pylori urease.
      Results were compared with a histological technique using the Romanowsky type
      (Diff-3) stain for detecting H pylori in both antral and body type gastric
      mucosa. A sensitivity of 94% and specificity of 100% using the agar gel test
      compared with 87% sensitivity and 99.3% specificity for the ultra-rapid endoscopy
      room test. Grading of H pylori in gastric biopsy specimens showed that the higher
      the histological grade, the more likely that the urease test would be positive.
      Both forms of urease tests have high specificity for detecting H pylori in
      gastric biopsy specimens, although the urea agar test has a higher sensitivity
      than the ultra-rapid test. Low numbers of H pylori in gastric biopsy specimens
      are the most important determinant of a false negative urease test.

PMID- 8157766
TI  - Relationship between clinical periodontal condition and the radiological
      appearance at 1st molar sites in adolescents. A 3-year study.
AB  - There has been considerable controversy about the incidence of periodontal
      disease in adolescents. It is noteworthy that there is disagreement between
      workers as to be radiological features that should be used to detect the earliest
      signs of periodontitis, and variation in the choice of criteria may have
      influenced the results of previous studies. The present project represents a 3
      year longitudinal assessment into the periodontal condition, assessed clinically
      and radiologically, of a group of adolescents. The radiographic investigations
      were carried out using vertical bitewing radiographs and, to reduce potential
      error caused by variation in film placement and tube alignment, individual
      impressions were used so that the film could be positioned accurately at repeat
      assessments. It was found that several of the radiographic features, such as the
      width of the periodontal ligament space and the angle of the interproximal bone
      crest relative to the tooth, similar to those previously attributed to the
      commencement of destructive periodontal changes, were found to be correlated with
      the maturation changes associated with the eruption of the adjoining permanent
      teeth. In spite of the use of impressions, some of the series of radiographs
      showed variation in tube alignment, and several of the above radiological
      features were also found to correlate with errors in radiographic technique. It
      was concluded that the various eruptive and maturation changes taking place
      during this stage in the adolescent dentition must be allowed for when looking
      for the earliest signs of periodontal destruction.

PMID- 8157767
TI  - A site-by-site follow-up study on the effect of controlled versus poorly
      controlled insulin-dependent diabetes mellitus.
AB  - In the present site-by-site follow-up study, the change in amount of approximal
      alveolar bone was assessed after 1 year from the baseline examination in 38 and
      after 2 years in 22 dentate subjects all with insulin-dependent diabetes
      mellitus. The diabetics, aged 35 to 56 years at baseline, had a history of a mean
      duration of 18 years of insulin-dependent diabetes mellitus and were under
      medical treatment at the outpatient clinic of the III Department of Medicine,
      University Central Hospital of Helsinki as well as at 2 diabetic clinics of the
      Helsinki Health Centre. Based upon their long-term medical records, 26 subjects
      were after 1 year, and 16 subjects after 2 years from the baseline, identified as
      having poorly controlled insulin-dependent diabetes (PIDD). At the 1-year
      examination, 12 subjects were classified as having controlled insulin-dependent
      diabetes (CIDD) as compared to 6 subjects at the 2-year examination. After 1 and
      2 years, from baseline, site-by-site measurements were recorded for plaque index
      scores, bleeding after probing, loss of attachment, and radiographic loss of
      alveolar bone. After 1 and 2 years from baseline, the PIDD subjects exhibited
      higher mean %s of sites with improved bleeding scores (P < 0.01, chi 2-test) than
      the CIDD subjects. At the 2-year examination, the mean % of sites with loss of
      approximal alveolar bone was greater in the PIDD than in the CIDD group (P <
      0.05, chi 2-test). The greatest differences between PIDD and CIDD subjects were
      found when recordings for only canines were analyzed at the 1- and 2-year
      examinations (P < 0.05, chi 2-test). The results of our current 2-year
      longitudinal site-by-site examinations confirm earlier results that poorly
      controlled insulin-dependent diabetes mellitus is strongly related to the amount
      of alveolar bone loss.

PMID- 8157768
TI  - The effect of systemically-administered flurbiprofen as an adjunct to
      toothbrushing on the resolution of experimental gingivitis.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely researched in an
      attempt to control periodontal diseases. This double-blind parallel group study
      investigated the effect of a systemic flurbiprofen preparation (100 mg daily),
      when combined with toothbrushing on the resolution of experimental gingivitis in
      human volunteers. 47 volunteers abstained from tooth cleaning for 21 days. On day
      21, 23 subjects were prescribed 100 mg of flurbiprofen daily whereas 24 subjects
      were prescribed placebo. In both groups, toothbrushing was re-introduced and all
      subjects used the Bass technique for 2 min each day. Both treatment regimens were
      continued for 7 days. Plaque indices, gingival indices and gingival crevicular
      fluid flow were assessed at baseline (day 0) and on days 21 and 27. There were no
      significant differences at p = 0.05 between the groups for plaque indices or
      gingival crevicular fluid flow. The flurbiprofen group, however, demonstrated
      greater resolution of gingival inflammation by day 27 when compared to the
      placebo controls (p = 0.04). The plasma levels of flurbiprofen in the test group
      showed mean concentrations of flurbiprofen of 4.7 (+/- 2.1) micrograms/ml at 1 h
      after dosing. After 6 h, this had fallen to 4.4 (+/- 1.6) micrograms/ml. It is
      concluded that these serum concentrations of flurbiprofen are sufficient to
      produce significant anti-inflammatory effects in the gingival tissues.

PMID- 8157769
TI  - Relationship between salivary blood group antigens, microbial flora and
      periodontal condition in young adults.
AB  - To investigate a possible role for salivary blood-group antigens in the relative
      frequencies of selected periodontal pathogens and commensal oral micro-organisms,
      we studied the clinical and microbiological condition in young adults with or
      without blood group reactive substances in saliva (secretors or non-secretors
      respectively). Clinical measurements were recorded at the Ramfjord teeth in 81
      1st-year dental students. In addition, presence of interproximal loss of
      attachment (LA) was assessed at sites with a pocket depth of > or = 4 mm.
      Microbiological samples were taken from one of the Ramfjord teeth (site without
      interproximal LA), from interproximal sites of > or = 4 mm in conjunction with
      LA, and from the saliva. The samples were analyzed for the presence of
      Actinomyces naeslundii, Actinomyces viscosus, Campylobacter rectus, Fusobacterium
      nucleatum, Peptostreptococcus micros, Prevotella intermedia, Porphyromonas
      gingivalis and Actinobacillus actinomycetemcomitans. Clinically, no statistically
      significant differences were found in the periodontal status between secretors
      (78% of our population) and non-secretors. Furthermore, the occurrence of the
      monitored micro-organisms was not correlated to the secretor status. It is
      concluded that bacterial colonization with the micro-organisms tested in this
      study, apparently occurred independent of secretor status. Among the periodontal
      pathogens, only P. intermedia was more frequently recovered from the saliva of
      subjects with interproximal LA (49%) than in those without (33%; p = 0.03). This
      finding was irrespective of the secretor status. Therefore, P. intermedia may be
      an important micro-organism in relation to the onset of periodontal destruction
      in young adults.

PMID- 8157770
TI  - Ex vivo studies of polymorphonuclear neutrophils from patients with early-onset
      forms of periodontitis. (I). Chemotactic assessment using the under agarose
      method.
AB  - The polymorphonuclear neutrophil (PMN) appears to be an important cell in the
      protection of the host from pathogenic periodontal microorganisms and, despite
      some reports to the contrary, it is generally assumed that early-onset forms of
      periodontal disease (including both juvenile and rapidly progressing
      periodontitis) are associated with a defect in PMN chemotactic behaviour. The
      purpose of the present study was to examine the peripheral PMN chemotactic
      behaviour, using the under agarose method, in 4 groups, namely healthy
      periodontium group (n = 7), gingivitis group (n = 8), early-onset periodontitis
      group (n = 17) and adult periodontitis group (n = 8). PMN from early-onset
      periodontitis patients showed normal random and chemotactic locomotory behaviour
      when compared with those of PMN from subjects of the other groups. No
      statistically significant difference could be found among the 4 studied groups,
      with regard to spontaneous and oriented migration.

PMID- 8157771
TI  - Mineral status of skeleton and advanced periodontal disease.
AB  - Studies of the effect of general bone loss on periodontal condition and on
      development of periodontal pockets suggest that there is no clear correlation
      between periodontal health or number of teeth and the general mineral status of
      the skeleton. In some reports, however, deep periodontal pockets have been
      correlated with good mineral status in the jawbones and skeleton. The purpose of
      this study of 227 healthy postmenopausal women aged 48 to 56 years was to
      determine whether advanced alveolar bone loss, diagnosed by panoramic
      radiographs, and periodontal probing depths or number of remaining teeth were
      correlated with the bone mineral status of the skeleton and cortical bone in the
      mandible. The results suggest that individuals with high mineral values in the
      skeleton seem to retain their teeth with deep periodontal pockets more easily
      than those with osteoporosis. This finding may especially motivate treatment of
      persons suffering from advanced periodontal disease but having good mineral
      status.

PMID- 8157772
TI  - The topography of the vascular systems in the periodontal and peri-implant
      tissues in the dog.
AB  - The present investigation reports an animal experiment the objective of which was
      to study the vascular topography of the periodontium and the peri-implant soft
      and hard tissues in the beagle dog. 2 beagle dogs were used. The right mandibular
      premolars were extracted and healing allowed for 3 months. 2 titanium fixtures
      a.m. Branemark were installed in the right premolar region. Abutment connection
      was performed 3 months later. The contra-lateral mandibular sites were used as
      tooth harboring control units. A 4-month period of meticulous plaque control was
      initiated. A clinical and radiographical examination was performed towards the
      end of this period and revealed that the gingiva and peri-implant mucosa were
      clinically healthy and that the bone tissue at teeth and implants had a normal
      height. The carotid arteries were perfused with a mixture of carbon and calf
      serum. 2 bucco-lingual sections, about 100-150 microns thick, and one mesio
      distal section comprising the junctional epithelium and underlying connective
      tissue were sampled. The sections were treated, cleared and examined in a
      microscope. The results of the present investigation demonstrated that the
      vasculature of the gingiva and the supracrestal connective tissue at teeth is
      derived from two sources, namely the supraperiosteal vessels lateral of the
      alveolar process and the vessels of the periodontal ligament. The blood vessels
      of the peri-implant mucosa were found to be terminal branches of larger vessels
      originating from the periosteum of the bone of the implant site.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8157773
TI  - The relation of preventive dental behaviors to periodontal health status.
AB  - Current recommendations for periodontal health maintenance emphasize
      toothbrushing, flossing and periodic dental checkups. The purposes of this study
      were to examine (1) the effects of these practices on periodontal health and (2)
      the relationships of demographic and socioeconomic variables with these behaviors
      and with periodontal health. Adults (n = 319) in the Detroit, Michigan tri-county
      area were asked how frequently they performed the 3 preventive behaviors. Levels
      of plaque, gingivitis, calculus, and periodontal attachment were then assessed
      during in-home dental examinations. There were no statistically significant
      differences in these health measures between those with acceptable and
      unacceptable brushing behavior. About 20% of the subjects reported acceptable
      flossing behavior, and these individuals had significantly less plaque and
      calculus than other participants. Over 3/4 of subjects reported having a dental
      checkup at least 1 x a year, and these persons were found to have significantly
      less plaque, gingivitis, and calculus compared to less frequent attenders.
      Acceptable brushing behavior was not associated with any particular demographic
      or socio-economic characteristic, while differences in acceptable flossing
      behavior were found among age groups. Frequencies of yearly dental checkups
      varied significantly within every demographic and socioeconomic characteristic.

PMID- 8157774
TI  - Quantitative aspects of the subgingival distribution of Actinobacillus
      actinomycetemcomitans in a patient with localized juvenile periodontitis.
AB  - The subgingival microflora in a patient with localized juvenile periodontitis was
      studied. Of the 97 sites investigated, 28 (29%) showed attachment loss. A
      correlation was found between the number of Actinobacillus actinomycetemcomitans
      cells and the clinical attachment level and probing pocket depth. Of the 97 test
      sites, 70 (73%) were positive for A. actinomycetemcomitans. Of the total number
      of A. actinomycetemcomitans cells isolated from this patient, more than 99% were
      found at sites with attachment loss, < 1% being present at sites without
      attachment loss. The mean percentage of A. actinomycetemcomitans was 21.2% at
      sites with attachment loss and 0.45% at sites without attachment loss. The
      distribution of Porphyromonas gingivalis showed a symmetrical pattern, being
      present at the 1st molar and 2nd premolar sites in all quadrants and at the lower
      incisor sites. This species was absent at multiple sites showing overt attachment
      loss.

PMID- 8157775
TI  - Microorganisms in polytetrafluoroethylene barrier membranes for guided tissue
      regeneration.
AB  - This study examined the microflora in 11 barrier membranes around teeth with
      furcation involvement or 2 to 3 wall intrabony defects and in 16 membranes around
      implants with various types of bony defects. Total viable counts and the
      occurrence of selected microbial species were determined by non-selective and
      selective culture and by DNA probes. Study sites were examined for probing pocket
      depth and attachment level. All tooth-associated membranes yielded high levels of
      microorganisms. 4 of 5 teeth with membranes harboring less than 10(8) organisms
      gained 3 mm or more in probing attachment, whereas 6 teeth with membranes with
      more than 10(8) organisms exhibited loss or only small gains in attachment. 3
      membranes with high levels of black-pigmented anaerobic rods lost 1 to 2 mm of
      attachment. Ten implant-associated membranes with no cultivable microorganisms
      demonstrated a mean probing gain of 4.9 mm. 6 implants with infected membranes
      only gained an average of 2.0 mm of supportive bone. The present findings
      underscore the importance of controlling or eliminating periodontal pathogens on
      barrier membranes in order to gain new attachment.

PMID- 8157776
TI  - Treatment of furcation defects. Guided tissue regeneration versus coronally
      positioned flap in mandibular molars; a pilot study.
AB  - The present study was designed to compare the healing results after treatment of
      buccal class II furcation defects in mandibular molars utilizing guided tissue
      regeneration (GTR) technique or coronally positioned flap (CPF) technique. The
      patient sample consisted of 8 subjects with 18 bilateral furcation defects in
      mandibular molars. At baseline, 6 and 12 months postoperatively assessments of
      plaque index, gingival index, probing pocket depths, probing attachment level and
      bleeding on probing were recorded. Radiographic assessment was performed using
      conventional radiographs and subtraction images at baseline and 12 months
      postoperatively. The furcation defects were randomly assigned in each patient to
      either the GTR or the CPF technique. 12 months postoperatively, there was a
      statistically significant reduction in probing pocket depths in the GTR treated
      teeth and a tendency to gain of probing attachment levels 6 months
      postoperatively. The CPF group showed a statistically significant reduction of
      probing pocket depths at 6 months and a tendency to reduction after 12 months.
      The radiological assessment demonstrated gain of interradicular bone tissue in 2
      furcation defects of the GTR group. Gain of bone tissue could not be demonstrated
      in the CPF group. No statistically significant differences were observed between
      the 2 treatment modalities.

PMID- 8157777
TI  - Clinical evaluation of a potassium nitrate dentifrice for the treatment of
      dentinal hypersensitivity.
AB  - The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment
      for dentinal hypersensitivity was evaluated in a double-blind study in 36
      Japanese subjects who complained of cold and/or tactile hypersensitivity. The
      subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate
      dentifrice (treated group) and the other 18 a vehicle paste (control group). Both
      groups were instructed to brush their teeth 2 x a day. The hypersensitivity
      levels of the affected teeth were assessed by 2 stimuli, one tactile and the
      other cold air, and by the perception of pain. The results of all 3 assessment
      methods indicated that the potassium nitrate dentifrice significantly decreased
      the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a
      rapid decrease of positive scores for both the cold air stimulus and the
      subjective symptoms appeared from week 2. Although a significant decrease of the
      assessment score was also observed in the control group, the reduction rate of
      the score was much greater in the treated group by all 3 assessment methods at
      weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12
      weeks' examination was noted in 67% of the subjects in the treated group, but in
      only 6% in the control group. These results suggest the usefulness of a 5%
      potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity.

PMID- 8157778
TI  - Cutaneous manifestations of diabetes mellitus.
AB  - Diabetes mellitus (DM) is a heterogeneous group of disorders characterized by a
      high serum glucose level and by disturbances of carbohydrate and lipid
      metabolism. It is estimated that 11 million persons in the United States have DM,
      90% of whom have non-insulin-dependent DM. At least 30% of persons with diabetes
      have some type of cutaneous involvement during the course of their chronic
      disease. This review classifies the cutaneous findings in DM into four
      categories: (1) skin diseases with strong to weak association with DM; (2)
      cutaneous infections; (3) cutaneous manifestations of diabetic complications; and
      (4) skin reactions to diabetic treatment. Each of these categories is reviewed as
      well as the pathophysiology of the normal and diabetic basement membrane for a
      better understanding of the cutaneous manifestations of DM.

PMID- 8157779
TI  - Pemphigus in remission: value of negative direct immunofluorescence in
      management.
AB  - BACKGROUND: Pemphigus vulgaris is characterized by relapses and remission, and
      there are currently no sensitive markers to predict remission. OBJECTIVE: Our
      purpose was to determine if direct immunofluorescence (DIF) performed during
      clinical remission of pemphigus is useful in management of the disease. METHODS:
      Twenty-eight patients with pemphigus that was in clinical remission (i.e.,
      patients who were taking low-dose prednisolone [10 mg/day] and had been blister
      free for at least 6 months) underwent DIF. Therapy was then discontinued and
      patients were prospectively followed up for 5 years. RESULTS: Twenty-two patients
      had negative results and six patients had positive results of DIF. The disease
      remained in remission in three quarters of the patients with negative results of
      DIF. Of those who had a relapse, intercellular C3 on DIF and oral lesions on
      initial presentation were important risk factors, and the relapses in patients
      with negative results of DIF were mild. The biopsy site was unimportant. All
      patients with positive results of DIF had major relapses within 3 months of
      cessation of therapy. CONCLUSION: DIF should be performed before therapy is
      discontinued. A negative DIF finding is a good indicator of remission in
      pemphigus.

PMID- 8157780
TI  - The ABCD rule of dermatoscopy. High prospective value in the diagnosis of
      doubtful melanocytic skin lesions.
AB  - BACKGROUND: The difficulties in accurately assessing pigmented skin lesions are
      ever present in practice. The recently described ABCD rule of dermatoscopy (skin
      surface microscopy at x10 magnification), based on the criteria asymmetry (A),
      border (B), color (C), and differential structure (D), improved diagnostic
      accuracy when applied retrospectively to clinical slides. OBJECTIVE: A study was
      designed to evaluate the prospective value of the ABCD rule of dermatoscopy in
      melanocytic lesions. METHODS: In 172 melanocytic pigmented skin lesions, the
      criteria of the ABCD rule of dermatoscopy were analyzed with a semiquantitative
      scoring system before excision. RESULTS: According to the retrospectively
      determined threshold, tumors with a score higher than 5.45 (64/69 melanomas
      [92.8%]) were classified as malignant, whereas lesions with a lower score were
      considered as benign (93/103 melanocytic nevi [90.3%]). Negative predictive value
      for melanoma (True-Negative divided by [True-Negative+False-Negative]) was 95.8%,
      whereas positive predictive value (True-Positive divided by [True-Positive+False
      Positive]) was 85.3%. Diagnostic accuracy for melanoma (True-Positive divided by
      [True-Positive+False-Positive+False-Negative]) was 80.0%, compared with 64.4% by
      the naked eye. Melanoma showed a mean final dermatoscopy score of 6.79 (SD, +/-
      0.92), significantly differing from melanocytic nevi (mean score, 4.27 +/- 0.99;
      p < 0.01, U test). CONCLUSION: The ABCD rule can be easily learned and rapidly
      calculated, and has proven to be reliable. It should be routinely applied to all
      equivocal pigmented skin lesions to reach a more objective and reproducible
      diagnosis and to obtain this assessment preoperatively.

PMID- 8157781
TI  - The inhibitory effects of topical chelating agents and antioxidants on nickel
      induced hypersensitivity reactions.
AB  - BACKGROUND: Nickel sensitivity is a common problem, often causing significant
      morbidity from chronic eczematous dermatitis. The main treatment, topical
      steroids, usually is unable to suppress the dermatitis completely. OBJECTIVE: Our
      purpose was to study the effects of "barrier" ointments containing either
      chelating agents (clioquinol or ethylenediaminetetraacetic acid [EDTA]) or
      antioxidants (ascorbic acid or alpha-tocopherol) and 1% hydrocortisone on nickel
      induced hypersensitivity reactions. METHODS: Nickel-sensitive subjects were
      challenged with nickel-containing coins coated with the desired barrier ointment
      and their inhibitory effects observed. Patients with bilateral hand or earring
      dermatitis explored the efficacy of these agents in clinical use. RESULTS:
      Clioquinol (3%) completely abolished the allergic reaction in all 29 subjects
      tested. EDTA (15%), ascorbic acid (20%), and alpha-tocopherol (10%) were less
      effective, and 1% hydrocortisone had no significant effect. In clinical use sites
      treated with a commercially available preparation containing 3% clioquinol and 1%
      hydrocortisone showed marked clinical improvement in all 10 subjects. CONCLUSION:
      Clioquinol is a potent inhibitor of nickel-induced hypersensitivity reactions and
      is feasible to use as a barrier ointment to block the allergenic effects of
      nickel in sensitive patients.

PMID- 8157782
TI  - Cleft lip mongolian spot: mongolian spot associated with cleft lip.
AB  - BACKGROUND: Mongolian spots in the cleft area of cleft lip have been found in
      some Japanese children. OBJECTIVE: Our purpose was to study the frequency of
      cleft lip mongolian spot in children with cleft lip of various severity. METHODS:
      Sixty-six babies with unilateral cleft lip were divided into three groups:
      namely, those with microform cleft lip (10 subjects), incomplete cleft lip (30
      subjects), and complete cleft lip (26 subjects). The incidence of cleft lip
      mongolian spot in the three groups was studied. RESULTS: Thirty-six babies (55%)
      had a cleft lip mongolian spot. The mongolian spot was observed in no patients
      with microform cleft lip, in 18 patients (60%) with incomplete cleft lip, and in
      18 patients (69%) with complete cleft lip. CONCLUSION: Cleft lip mongolian spot
      appears in high incidence when the cleft goes beyond the vermilion border.

PMID- 8157783
TI  - Disease outcome in workers with occupational skin disease.
AB  - BACKGROUND: Occupational contact dermatitis (OCD) contributes significantly to
      the burden of occupational disease, but there is little known about prognostic
      factors. OBJECTIVE: The study was designed to determine the health status of
      workers with OCD at least 2 years after diagnosis and to identify risk factors
      related to prognosis. METHODS: A questionnaire study was conducted of workers
      with a diagnosis of work-related skin disease. RESULTS: Of the 201 workers with
      OCD, 76% noted improvement and 40% reported that they were currently free of any
      eruption. Approximately one third noted that their skin disease interfered with
      household, work, or recreational activities. The key prognostic factor appeared
      to be sex because women reported a better outcome. Diagnosis and atopic status
      tended to be related to some outcomes, whereas age was not. CONCLUSION:
      Examination of other possible factors, some of which may be associated with sex,
      that might affect outcome should be undertaken to gain a better understanding of
      possible management strategies. A retrospective study has methodologic
      limitations and a prospective intervention trial should yield more information.

PMID- 8157784
TI  - Acquired reactive perforating collagenosis. Report of six cases and review of the
      literature.
AB  - BACKGROUND: Reactive perforating collagenosis (RPC) is characterized by
      transepithelial elimination of altered collagen. Two types have been recognized:
      the childhood form and the adult form. OBJECTIVE: Our purpose was to review the
      associated disorders, evaluate the possible causes, and set criteria for the
      diagnosis of the disease. METHODS: The clinical and pathologic findings of six
      patients with the adult form of RPC are reviewed. The literature on this subject
      is compared with our findings. RESULTS: Pruritus was reported in all cases.
      Treatment of pruritus cleared the lesions in many patients. This is the first
      report of an association between RPC and hyperparathyroidism, hypothyroidism,
      liver disorders, and neurodermatitis. CONCLUSION: Various disorders can be
      associated with the adult form of RPC. Pruritus is the common factor among all
      types. Control of itching might be helpful for clearing the lesions. We propose
      the following diagnostic criteria for acquired RPC: (1) histopathologic findings
      of elimination of necrotic basophilic collagen tissue into a cup-shaped epidermal
      depression, (2) clinical presentation of umbilicated papules or nodules with a
      central adherent keratotic plug, and (3) onset of skin lesions after the age of
      18 years.

PMID- 8157785
TI  - Pigment cell transplantation for treatment of vitiligo: a progress report.
AB  - BACKGROUND: Because available treatments for vitiligo generally provide
      unsatisfactory results, the search for viable therapeutic alternatives continues.
      OBJECTIVE: Our purpose was to evaluate several transplantation procedures with
      cultured autologous melanocytes for their practicality in treating patients with
      vitiligo. METHODS: Twenty-seven patients with stable or active vitiligo were
      treated after superficial dermabrasion with application of suspensions of
      autologous cultured melanocytes, melanocyte-keratinocyte mixtures, or epidermal
      sheets established in vitro. RESULTS: Regardless of disease activity, use of each
      method resulted in repigmentation to a similar degree and without scarring in all
      patients. Melanocyte suspensions offer several advantages: They are easily
      prepared, can be applied in a controlled manner, permit coverage of large areas,
      and produce a homogeneous skin color that affords the best cosmetic restoration.
      The ultrastructure of transplant sites resembled that of uninvolved skin, with
      one exception: the melanocytes were located slightly higher than in uninvolved
      skin. CONCLUSION: Application of cultured autologous melanocytes to lightly
      abraded skin is an advantageous addition to the treatments available for patients
      with vitiligo.

PMID- 8157786
TI  - A double-blind, placebo-controlled clinical trial to evaluate the safety and
      efficacy of thymopentin as an adjunctive treatment in atopic dermatitis.
AB  - BACKGROUND: Multiple immunologic abnormalities such as impaired T-cell function,
      elevated serum IgE level, and increased interleukin 4 production have been
      demonstrated in patients with atopic dermatitis. OBJECTIVE: As part of a 12-week,
      multicenter, double-blind, placebo-controlled clinical trial, we evaluated the
      safety and efficacy of thymopentin (Timunox) as an adjunctive treatment in
      patients with severe atopic dermatitis. METHODS: Thirty-nine patients at least 2
      years old with severe atopic dermatitis on a minimum of 20% of their cutaneous
      surface area were randomly selected to receive either thrice-weekly subcutaneous
      injections of thymopentin, 50 mg, or placebo. Use of triamcinolone 0.1% or
      hydrocortisone 1.0% cream and oral antihistamines were permitted during this
      trial. RESULTS: After 12 weeks, thymopentin-treated patients had significantly
      greater improvement than those receiving placebo. No thymopentin-related adverse
      events occurred. CONCLUSION: Thymopentin may be a safe effective adjunct to
      therapy in patients with severe atopic dermatitis.

PMID- 8157787
TI  - Pentoxifylline.
AB  - Pentoxifylline (oxpentifylline) is a methylxanthine derivative with potent
      hemorrheologic properties. In the United States it is marketed for the treatment
      of intermittent claudication. Human and animal studies have shown that
      pentoxifylline therapy results in a variety of physiological changes at the
      cellular level, which may be important in treating a diverse group of human
      afflictions. Immune modulation includes increased leukocyte deformability and
      chemotaxis, decreased endothelial leukocyte adhesion, decreased neutrophil
      degranulation and release of superoxides, decreased production of monocyte
      derived tumor necrosis factor, decreased leukocyte responsiveness to interleukin
      1 and tumor necrosis factor, inhibition of T and B lymphocyte activation, and
      decreased natural killer cell activity. Hypercoagulable states improve through
      decreased platelet aggregation and adhesion, increased plasminogen activator,
      increased plasmin, increased antithrombin III, decreased fibrinogen, decreased
      alpha 2-antiplasmin, decreased alpha 1-antitrypsin, and decreased alpha 2
      macroglobulin. Wound healing and connective tissue disorders may respond to an
      increase in fibroblast collagenases and decreased collagen, fibronectin, and
      glycosaminoglycan production. Fibroblast responsiveness to tumor necrosis factor
      is also diminished. Potential medical uses of pentoxifylline are reviewed.

PMID- 8157788
TI  - Chromosomal mosaicism in two patients with epidermal verrucous nevus.
      Demonstration of chromosomal breakpoint.
AB  - Linear epidermal nevi are hamartomas that originate in embryonic ectoderm. For
      epidermal nevi associated with involvement of other systems, such as the skeleton
      or central nervous system, the term epidermal nevus syndrome has been introduced.
      Chromosomal aberrations have been suggested but not proven as an underlying
      cause. We performed cytogenetic studies of skin cells from two unrelated men who
      had a verruciform epidermal nevus. Variegated translocation mosaicism with an
      identical breakpoint localized at the long arm of chromosome 1 was present in
      both patients. Normal skin and blood lymphocytes showed normal karyotypes.

PMID- 8157789
TI  - Cutaneous manifestations of non-01 Vibrio cholerae septicemia with
      gastroenteritis and meningitis.
AB  - A 58-year-old man with diabetes had fever and chills 5 days after ingestion of
      raw seafood. Nausea, vomiting, watery diarrhea, bilateral calf pain, and neck
      stiffness subsequently developed. Generalized edema and ecchymotic patches with a
      vesiculobullous eruption appeared on the extremities. Four blood cultures were
      positive for Vibrio cholerae non-01. The patient was successfully treated with
      antibiotics. This is the first documented case of V. cholerae non-01 septicemia
      with cutaneous lesions and meningitis in Taiwan.

PMID- 8157790
TI  - Adjuvant radiotherapy after excision of cutaneous squamous cell carcinoma.
AB  - Most cutaneous squamous cell carcinomas (SCCs) of the trunk and extremities are
      small enough to be cured by simple surgical excision. Because the risk of
      metastasis of SCCs of the head and neck arising from mucosal surfaces is higher
      than the risk of metastasis of SCCs arising from cutaneous surfaces, it may be
      more appropriate to review case reports of the trunk and extremities separately
      from those of the head and neck when seeking prognostic indicators. A small group
      of advanced lesions, however, is more difficult to treat and has an increased
      risk of local recurrence or metastasis and a poorer prognosis. We describe a
      patient with high-risk cutaneous SCC who is disease-free 1 year after adjuvant
      radiotherapy subsequent to excision by Mohs micrographic surgery. This report
      discusses prognostic indicators of cutaneous SCC and suggests adjuvant modalities
      for the treatment of high-risk disease after surgical excision. Radiotherapy is a
      rational choice as adjuvant therapy for the treatment of high-risk cutaneous SCC
      after excision.

PMID- 8157791
TI  - Axillary string phlebitis in pregnancy: a variant of Mondor's disease.
AB  - A 28-year-old pregnant woman had acute superficial thrombophlebitis in the right
      axilla. Aside from pregnancy, there were no risk factors for hypercoagulability.
      This case is presented as a variant of Mondor's disease. The pendulous breasts
      associated with her pregnancy and strenuous lifting may have predisposed the
      patient to the disease.

PMID- 8157792
TI  - Is pentoxifylline the drug of the decade?

PMID- 8157793
TI  - Through the eye of the needle: saving your running intradermal suture.

PMID- 8157794
TI  - Pemphigoid vegetans.

PMID- 8157795
TI  - Pemphigus vulgaris after initiation of psoralen and UVA therapy for psoriasis.

PMID- 8157796
TI  - Unilateral plantar erythema nodosum.

PMID- 8157797
TI  - Becker's nevus associated with chromosomal mosaicism and congenital adrenal
      hyperplasia.

PMID- 8157798
TI  - Reactions of uninvolved psoriatic skin and normal skin to ultraviolet radiation.

PMID- 8157799
TI  - Successful treatment of chronic bullous dermatosis of childhood with colchicine.

PMID- 8157800
TI  - Absence of carbohydrate intolerance in granuloma annulare.

PMID- 8157801
TI  - Efficacy of terbinafine 1% cream in the treatment of moccasin-type tinea pedis:
      results of placebo-controlled multicenter trials.

PMID- 8157802
TI  - Chemical peeling as adjuvant therapy for facial neurotic excoriations.

PMID- 8157803
TI  - Grinspan's syndrome.

PMID- 8157804
TI  - Angiotensin-converting enzyme inhibitors.

PMID- 8157805
TI  - Conceptual differences on the occurrence of internal malignancies in the FAMMM
      syndrome.

PMID- 8157806
TI  - Cutaneous markers of internal malignancy.

PMID- 8157807
TI  - Skin markers of malignancy.

PMID- 8157808
TI  - Recurrent cellulitis.

PMID- 8157809
TI  - A meta-analysis of two different trials on posterior resin-bonded bridges.
AB  - In a meta-analysis the results of two different trials on posterior resin-bonded
      bridges (PRBBs) were combined. The common experimental variable 'preparation
      form' and the variable 'location' were combined for this analysis. The meta
      analysis showed a highly significant effect for the variable 'location' (P <
      0.001). Although the experimental variable 'preparation form' had no significant
      influence in the separate trials, the combined study revealed a significant
      effect for this variable on the retention of PRBBs (P = 0.03).

PMID- 8157810
TI  - Meta-analysis on long-term clinical performance of posterior composite
      restorations.
AB  - Meta-analysis is a formalized method of combining results of different studies to
      provide conclusions about the effectiveness of a treatment modality. The aims of
      this study were to use meta-analysis to determine the clinical performance of
      posterior composite restorations using the assessment criteria of the USPHS
      guidelines by combining data from selected multiple studies and to estimate the
      overall survival rates of posterior composite restorations over time. A computer
      aided search of the literature revealed 97 publications on clinical trials of
      posterior composites in the last 10 years. Following specific selection criteria,
      which included the year and language of publication, duration of study, class of
      cavities restored and type of resin composite material used and clinical
      characteristics assessed; 16 studies were found to be suitable for, and included
      in a meta-analysis. These involved eight different resin composite materials.
      Assessment criteria data were extracted from each selected study and tabulated on
      the basis of years of follow-up and materials. The criteria were coded as binary
      variables. Homogeneity amongst studies was assessed using Woolf's statistic prior
      to combining the data. Weighted average proportions and standard errors were
      determined for each of the assessment criteria. Using Kaplan-Meier estimates,
      survival analyses of individual assessment criteria (outcomes) for two posterior
      composite materials were conducted and the resultant survival curves for these
      outcomes for the two materials are presented. Considering the limited number of
      studies of variable length available for meta-analysis, the results indicate
      generally high clinical performance of the various posterior composites for the
      number of outcomes analysed.

PMID- 8157811
TI  - Attitudes of dental students towards elderly people.
AB  - Questionnaires were distributed to first, third and fifth year dental students at
      two British dental schools, to assess their attitudes towards the elderly. A
      second follow-up questionnaire was given 1 year later to the five student years
      attending one of these dental schools, to compare attitudes and estimate how they
      affected their perceptions of treating this section of the community. In both
      questionnaire surveys, clinical dental students had a more positive attitude
      towards the elderly than did students in the non-clinical years of the course. In
      those students who had received both questionnaires on consecutive years, there
      was an improved attitude score. There were no significant differences in the
      attitudes of male and female students.

PMID- 8157812
TI  - Permeability and microleakage of Class II resin composite restorations.
AB  - The aim of this study was to evaluate the variations in microleakage of large
      Class II (MOD) restorations over time. Three different combinations of dentine
      bonding agents and posterior resin composites which had previously shown promise
      were used: Vitrebond/Scotchbond 2 plus P50, Tripton plus Occlusin and Clearfil
      Photo Bond plus Clearfil Photo Posterior. Conventional Class II cavities were
      prepared in freshly extracted third molars. All gingival margins were terminated
      at the cemento-enamel junction. A fluid-under-pressure apparatus connected with
      the pulp chamber of each tooth was used to evaluate the permeability and marginal
      leakage of the restorations at 0.069 MPa. Microleakage was tested after insertion
      of restorations at 2, 15, 45, 150 min, after 1, 2, 7, 14 days, after 1, 2, 3
      months, after thermal cycling and 10 months later, after occlusal loading.
      Finally, all specimens were exposed to silver nitrate solution to measure
      microleakage as dye penetration. Immediately after insertion of the restorations,
      all the materials showed a higher microleakage than after 1-2 days. After 4-8
      weeks, all the restorations exhibited an increased permeability suggesting that
      hygroscopic expansion was not sufficient to keep pace with hydrolytic degradation
      of the restorations. Neither thermocycling or occlusal stresses increased the
      microleakage of the restorations.

PMID- 8157813
TI  - Dental materials: 1992 literature review.

PMID- 8157814
TI  - Effects of coupling agents on mechanical properties of metal oxide
      polymethacrylate composites.
AB  - The effects of several coupling agents on the mechanical properties of metal
      oxide-polymethacrylate composites reinforced with titanium dioxide (TiO2),
      aluminium oxide (Al2O3), silica (SiO2) and zirconium dioxide (ZrO2), as fillers
      for opaque resins were assessed. The prepared composites consist of 24.75 wt%
      triethyleneglycol dimethacrylate (TEGDMA), 24.75 wt% 1,6-bis(methacryloxy-2-
      ethoxycarbonylamino)-2,4,4-trimethylhexane (UDMA), 0.5 wt% benzoyl peroxide (BPO)
      and 50 wt% metal oxide filler. Three methacrylate coupling agents-
      methoxydiethyleneglycol trimethacryloyl titanate, 3-trimethoxysilylpropyl
      methacrylate and 2,2-di(allyloxymethyl)butyl trimethacryloyl zirconate--were used
      for surface treatment of TiO2, SiO2 and ZrO2, respectively, while Al2O3 was
      treated with 4-methacryloxyethyl trimellitate anhydride (4-META). 4-META was also
      adopted as a coupler for TiO2, SiO2 and ZrO2 powders. Compressive and transverse
      strength specimens were prepared with the use of coupled or untreated filler and
      heat cured at 110 degrees C and 0.5 MPa for 30 min. All coupled metal oxide
      composites had significantly higher compressive and transverse strengths than did
      untreated composites after 1 month's immersion in 37 degrees C water. Scanning
      electron microscopy (SEM) of fractured TiO2 composite surfaces after storage in
      water for 1 month showed an interface failure between TiO2 filler and matrix
      resin for untreated TiO2 composite and cohesive failures within the resin for
      treated specimen. Similar results were observed with silanated SiO2 composite.
      However, cohesive and interface failures were seen in zirconated ZrO2- and 4-META
      coupled Al2O3 composites. Thus, titanated TiO2-polymethacrylate composite may be
      useful as a composite pigment for opaque resin materials.

PMID- 8157815
TI  - The control of fibrosis in systemic sclerosis: a strategy involving extracellular
      matrix, cytokines, and growth factors.

PMID- 8157817
TI  - An immunohistochemical study of BCA-225 in various skin cancers.
AB  - We performed an immunohistochemical study of BCA-225, which is a glycoprotein
      secreted by the T47D breast carcinoma cell line and recognized by monoclonal
      antibody BRST-1 (clone name: CU-18), in normal skin and various skin cancers. In
      normal skin, BCA-225 was positive only in the secretory portion of both eccrine
      and apocrine glands and in mature cells of the sebaceous gland. We observed 10
      cases of squamous cell carcinoma of the skin, 10 cases of basal cell carcinoma
      without sebaceous differentiation, 3 cases of basal cell carcinoma with sebaceous
      differentiation, 6 cases of malignant trichilemmoma, 8 cases of eccrine
      porocarcinoma, 3 cases of ductal carcinoma, 1 case of malignant clear cell
      hidradenoma, 1 case of apocrine adenocarcinoma, 6 cases of extra-ocular sebaceous
      carcinoma, 5 cases of extramammary Paget's disease with underlying
      adenocarcinoma, and 11 cases of extramammary Paget's disease without underlying
      adenocarcinoma. Most of the cases of sweat gland carcinoma, basal cell carcinoma
      with sebaceous differentiation, sebaceous carcinoma, and extramammary Paget's
      disease were positive for BCA-225, while none of the cases of squamous cell
      carcinoma, basal cell carcinoma without sebaceous differentiation, or malignant
      trichilemmoma were positive. Based on these findings, we believe that BCA-225 is
      useful in distinguishing tumors with sweat gland and sebaceous differentiation
      and extramammary Paget's disease from tumors without such differentiation.

PMID- 8157816
TI  - Applications of DNA flow cytometry and fluorescence in situ hybridization using a
      chromosome-specific DNA probe on paraffin-embedded tissue sections of primary
      malignant melanomas.
AB  - We have applied DNA flow cytometric analysis to paraffin-embedded tissue sections
      of primary malignant melanomas. Conventionally, flow cytometric analysis of
      paraffin-embedded tissue sections has been done by the method of Hedley et al. We
      added ultrasound treatment to the method of Hedley et al. and a lower value of
      coefficient of variation was shown. Furthermore, a new technique, fluorescence in
      situ hybridization with a chromosome-specific repetitive DNA probe, was used for
      the analysis of chromosomal numerical aberrations in the same paraffin-embedded
      tissue sections. The DNA flow cytometric analysis showed that in 8 cases six
      primary malignant melanomas were of the aneuploid pattern and two cases of
      lentigo maligna (melanoma in situ) were of the diploid pattern. By fluorescence
      in situ hybridization, the two cases with the diploid pattern had spots/nucleus
      of 1.28 and 1.12, and those with the aneuploid pattern had spots/nucleus from
      2.01 to 2.27. Only one nodular melanoma in an aneuploid case showed spots/nucleus
      of 1.71. These data indicate that fluorescence in situ hybridization with
      chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the
      analysis of interphase nuclei of solid human tumors and may be useful for the
      study of tumor cell heterogeneity.

PMID- 8157818
TI  - Generalized skin reaction following tinea pedis (dermatophytids).
AB  - An 11-year-old boy presented with inflamed tinea pedis followed by a generalized
      id type skin eruption, with disappearance of the rash after treatment of the
      mycotic foot lesions. The pathogenesis of this process is not precisely known.
      Fungal infection was not detected from the generalized skin lesions. Various
      clinical forms of dermatophytid reaction are discussed.

PMID- 8157819
TI  - Sebaceous epithelioma.
AB  - An 83-year-old woman had developed an asymptomatic, yellowish, dome-shaped skin
      tumor on her scalp which had enlarged for a period of 60 years to 10 x 10 x 10 mm
      in size. Histopathologically, the tumor consisted of undifferentiated basaloid
      cells, differentiated sebaceous cells and transitional cells. Although the
      basaloid cells resembled those of basal cell epithelioma (BCE), the tumor was
      distinct from BCE in the following points; existence of cystic spaces, no
      peripheral palisading, no proliferation of connective tissue stroma, and no
      tendency toward local invasion. Immunohistochemical studies using antikeratin
      monoclonal antibodies revealed that the tumor contained both the keratin types of
      BCE and of sebaceous glands. Electron microscopically, the tumor cells contained
      lipid droplets and keratohyaline granules in their cytoplasm. It is suggested
      that "sebaceous epithelioma" is a benign skin tumor which may be distinguished
      cytologically from BCE.

PMID- 8157820
TI  - Scrofuloderma of the scalp, psoas abscess, and caries spine: an unusual
      association.
AB  - An unusual association of scrofuloderma of the scalp, psoas abscess, and caries
      spine was seen in a 4-year-old girl. The diagnosis was confirmed by relative and
      absolute criteria. The peripheral T-lymphocytes and their subsets were within
      normal limits, although her immunohistopathological changes indicated an
      intermediary response across the spectrum depicting an unstable immunity. This
      may have been responsible for the silent spread of Mycobacterium tuberculosis and
      the current association.

PMID- 8157821
TI  - Febrile ulceronecrotic Mucha-Habermann's disease.
AB  - Febrile ulceronecrotic Mucha-Habermann's disease (FUMH) was first described by
      Degos in 1966. In the literature, nine cases of FUMH have been reported in both
      children and adults. We report a 16-year-old boy with the febrile ulceronecrotic
      type. A review of the nine cases in the literature showed acute necrotic lesions,
      as well as rare complications such as fever, superinfected lesions and viral
      infection which are not as common in pityriasis lichenoides et varioliformis
      acuta. There is no definitive treatment, but systemic corticosteroid,
      methotrexate, antibiotics (tetracycline, erythromycin), aciclovir, and 4,4
      diaminodiphenyl sulfone (DDS) have been frequently used. The most common
      histologic feature is mononuclear perivascular infiltrates consisting of T
      lymphocytes. The etiology is not known, but a hypersensitivity reaction, possibly
      to an infectious agent, is suggested.

PMID- 8157822
TI  - Effects of krestin (PSK) on tumorigenesis induced by two-stage and complete
      chemical carcinogenesis.
AB  - The effects of PSK on tumorigenesis in mouse skin were investigated either when
      mouse skins were initiated by benzo(a)pyrene and promoted by 12-O-tetradecanoyl
      phorbol-13-acetate (Group I, two-stage carcinogenesis) or when both initiated and
      promoted by benzo(a)pyrene (Group II, complete carcinogenesis). Twelve mice in
      each group were fed chow with or without 0.4% PSK. This concentration of PSK was
      determined by calculation to give mice enough PSK to exert antitumorigenic
      activity without cytotoxicity. By the end of the experimental periods (26 weeks),
      two carcinoma-burdened mice in Group I without PSK were dead, but no carcinomas
      at all were identified in the mice fed with PSK, although considerable numbers of
      papillomas developed in both groups. In Group II, carcinomas started to evolve at
      the 15th week of the experiment regardless of PSK feeding. The number of
      carcinomas observed in the mice fed with PSK in Group II was statistically
      significantly lower than that in the mice fed without PSK. Histologically, mild
      inflammatory infiltrations were seen around the papillomas, and moderate to dense
      infiltrations, mainly composed of neutrophils, T lymphocytes, and macrophages,
      were observed in squamous cell carcinomas. There were apparently no significant
      differences in the number of the infiltrating cells around carcinomas in PSK (+)
      and PSK (-) groups in both early and fully developed lesions. However,
      considerable numbers of cells infiltrating into the nests were observed in the
      early lesions of elicited carcinomas in the mice fed with PSK, while such cells
      were rarely seen in carcinoma nests in the group without PSK at that
      stage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157823
TI  - Generalized argyria after habitual use of AgNO3.
AB  - Generalized argyria, the systemic dissemination and tissue deposition of silver
      containing particles, is characterized by slate gray discoloration of skin, most
      pronounced in sun exposed areas. A 33-year-old woman visited our dermatologic
      clinic complaining of frequent oral ulceration for 10 years and generalized
      discoloration of her skin for 5 years. She had had her tongue painted with silver
      nitrate repeatedly 6 years ago for the treatment of oral ulcers. Physical
      examination showed slate gray discoloration of her skin, most pronounced on the
      face and neck. The oral mucosa, tongue, sclera, and conjunctiva also had a
      slightly blue-gray discoloration. Biopsy specimens from the oral mucosa and
      forearm revealed small brown-black granules scattered in the dermis and basal
      lamina of eccrine sweat glands, blood vessels, and hair follicles under the light
      microscope. Tiny black granules were most numerous in the basal laminae of
      vessels in electron microscopic observation. Energy dispersive X-ray
      microanalysis (EDXA) confirmed that many of the granules contained silver.

PMID- 8157824
TI  - Rudimentary polydactyly.
AB  - A case of rudimentary polydactyly on the radial aspect of the thumb of a 4-year
      old male was examined. Histologic examination revealed hyperkeratosis and
      acanthosis in the epidermis and large numbers of nerve bundles in the dermis.
      With immunoperoxidase staining for S-100 protein, the nerve corpuscles were
      positively stained. We think that rudimentary polydactyly is a kind of congenital
      traumatic neuroma and that the possible cause may be intrauterine amputation.

PMID- 8157825
TI  - Pemphigus vulgaris associated with autoimmune hemolytic anemia and elevated TNF
      alpha.
AB  - A 76-year-old female was admitted with many bullae and erythema on her trunk and
      extremities. A biopsy specimen showed significant intercellular edema in the
      lower epidermis and eosinophilic infiltration into the dermis and the epidermis.
      Immunofluorescent staining revealed the deposition of IgG in the intercellular
      area of her prickle cells. From these histologic findings and the typical
      clinical features, we diagnosed her as having pemphigus vulgaris. Examination of
      her blood revealed that she also suffered from autoimmune hemolytic anemia.
      Despite intensive treatment with prednisolone, she finally died. This case is of
      interest because of its rarity and the TNF alpha detected significantly in the
      blister fluid of this patient.

PMID- 8157826
TI  - Wax ester secretion rates and plasma dehydroepiandrosterone sulfate levels in
      children.

PMID- 8157827
TI  - Comedone extraction with trichloracetic acid.

PMID- 8157828
TI  - 'Royal mineral succedaneum' revisited.

PMID- 8157830
TI  - Ethical responsibility.

PMID- 8157829
TI  - Alzheimer's patients.

PMID- 8157831
TI  - Other dental professionals?

PMID- 8157832
TI  - Using rubber dam.

PMID- 8157833
TI  - The licensure question.

PMID- 8157834
TI  - Managing TMD.

PMID- 8157835
TI  - Practice management plus.

PMID- 8157836
TI  - Digital radiology.

PMID- 8157837
TI  - Scientists study DNA technology for treating periodontal disease.

PMID- 8157838
TI  - Dentists and the patients who love them: professional and patient views of
      dentistry.
AB  - Dentistry has long been identified with the bizarre or sadistic in books, movies
      and sitcoms. But how do dentists see themselves? How do patients view their
      dentists? Professional qualities of the ideal dentist, the surveyed dentist and
      the dentists of surveyed patients are discussed.

PMID- 8157839
TI  - Periodontitis and aging: reviewing recent evidence.
AB  - This review critically examines recent research on the relation between age and
      periodontitis. It concludes that some loss of periodontal attachment and alveolar
      bone is to be expected in older persons, but age alone in a healthy adult does
      not lead to a critical loss of periodontal support. Although moderate loss of
      alveolar bone and periodontal attachment is common in the elderly, severe
      periodontitis is not a natural consequence of aging.

PMID- 8157840
TI  - Sensitivity answers sought in amalgam alloy microleakage study.
AB  - Sensitivity often occurs shortly after an amalgam restoration is placed. This
      phenomenon has been related in part to microleakage at the amalgam/tooth
      interface. When microleakage characteristics of a large number of commercially
      available dental amalgams were examined, results showed wide variation in the
      amount of microleakage.

PMID- 8157841
TI  - Resin to metal bonding: overcoming esthetic problems.

PMID- 8157842
TI  - Dental complications after treating patients with AIDS.
AB  - Post-procedural complications were assessed for 331 patients with AIDS after a
      wide range of outpatient dental procedures. Only patients with a CD4+ cell count
      < or = 200 cells/mm3 were included. Patients' charts were reviewed
      retrospectively by the treating dentist. The overall complication rate was 0.9
      percent.

PMID- 8157843
TI  - Achieving implant reconstruction through bilateral mandibular nerve
      repositioning.
AB  - Grafting is one treatment option for patients who have insufficient bone for
      implant placement. However, repositioning the neurovascular bundle also can allow
      for placement of endosseous implants. This case illustrates bilateral
      repositioning of the mandibular nerves and subsequent implant placement.

PMID- 8157844
TI  - Ceramic vs. porcelain-fused-to-metal crowns: give your patients a choice.

PMID- 8157845
TI  - Location and logo: impressions are everything.
AB  - Several factors help make an attractive impression to potential patients.
      Considerations when naming your practice, designing a logo and choosing a
      location are discussed.

PMID- 8157846
TI  - Texas board absolved in discrimination case.

PMID- 8157847
TI  - Pennsylvania dentist. Hospital not liable for defective prosthesis.

PMID- 8157848
TI  - How income, employment, insurance affect older Americans' dental care.
AB  - Analyzing data from the national survey of oral health shows that seniors who
      need health care coverage are least likely to have this coverage. With little
      government support for dental care, older Americans with lower incomes may delay
      or avoid dental treatment.

PMID- 8157849
TI  - Intense sweeteners use and weight change among women: a critique of the Stellman
      and Garfinkel study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the work of Stellman and
      Garfinkel who speculated, based on epidemiologic data, that users of intense
      sweeteners are more likely than nonusers to gain weight. METHODOLOGY: We analyzed
      the study's design and statistical analysis to determine whether the conclusions
      of Stellman and Garfinkel were supported by the data. RESULTS: Several
      methodological flaws and inappropriate statistical analyses were identified.
      These included: use of data from an unrelated study for which they were not
      intended; failure to correct for bias due to convenience sampling; use of data
      from a subpopulation without validation; and stratification of subjects by
      outcome data. CONCLUSION: Our analysis indicates that the data from the study in
      question do not allow one to draw conclusions about a relationship between use of
      intense sweeteners and weight change. Furthermore, data from well-designed
      clinical trials have shown that aspartame is not associated with weight gain, and
      when used as part of a balanced deficit diet, can facilitate weight loss.

PMID- 8157850
TI  - Supplement use, other dietary and demographic variables, and serum vitamin C in
      NHANES II.
AB  - OBJECTIVE: Our objective was to evaluate the effect of regular use of nutritional
      supplements on serum vitamin C levels in a multivariable regression model, taking
      into account other dietary and demographic variables which may affect nutritional
      status. METHODS: We analyzed NHANES II data for subjects age 3 to 74. Analysis
      was limited to regular supplement users and nonusers, excluding irregular users.
      Multivariable regression analysis was performed with SUDAAN, incorporating sample
      weights and accounting for the complex survey design. RESULTS: Regular supplement
      users had substantially higher serum vitamin C levels than nonusers (p < 0.001).
      The magnitude of the effect of supplement use on serum vitamin C was 0.23-0.33
      mg/dL in children and teens, and 0.36-0.46 mg/dL in adults. In adults who smoked,
      bottom quartile vitamin C levels were 0.3 mg/dL in men and 0.4 mg/dL in women who
      did not use supplements, compared to 0.9 and 1.1 mg/dL in regular supplement
      users. There was a significant interaction of smoking and supplement use in men
      (p < 0.001). CONCLUSION: Regular supplement use has a strong impact on serum
      vitamin C levels, independent of other dietary and demographic characteristics of
      supplement users which may favor improved nutritional status.

PMID- 8157851
TI  - Fruit and vegetable food frequencies by fourth and fifth grade students: validity
      and reliability.
AB  - OBJECTIVE: Due to the increased emphasis on fruit and vegetable (F+V) consumption
      and a desire to use the simplest dietary assessment method appropriate to
      determine F+V intake, we assessed the reliability and validity of weekly and
      monthly fruit and vegetable food frequency questionnaires (F+V FFQ) among fourth
      and fifth grade students by comparing them to food records previously validated
      through school lunch observations. METHODS: The multiethnic sample (primarily
      African-American and Caucasian) included predominantly lower-middle socioeconomic
      students from 10 classes at one elementary school. F+V FFQ were printed on
      optical scanning forms and classroom administered on two occasions. Students
      completed preprinted food record forms at school and received new forms weekly.
      To allow comparison between the F+V FFQ and food records, a dietitian abstracted
      information from the records according to a written protocol and transferred it
      to F+V FFQ forms covering respective time periods. F+V FFQ were converted to
      estimated daily servings and aggregated to create five F+V indices plus three
      summary indices. Statistical analyses included Spearman correlations and paired t
      tests. RESULTS: Students demonstrated acceptable reliability in completing food
      records as well as weekly and monthly F+V FFQ; however, validity was unacceptable
      for both F+V FFQ versions due to significant overreporting. CONCLUSION: Of the
      two methods studied, the food record procedure is preferred over the FFQ
      procedure for collecting self-reported F+V consumption data among fourth and
      fifth grade students.

PMID- 8157852
TI  - Medium- and long-chain triglycerides have different effects on the synthesis of
      tumor necrosis factor by human mononuclear cells in patients under total
      parenteral nutrition.
AB  - OBJECTIVE: Lipid emulsions containing both long- and medium-chain triglycerides
      (LCT/MCT) have been used in total parenteral nutrition (TPN) regimens and seem to
      have certain advantages for seriously ill patients. The aim of the present study
      was to investigate the effect of lipid emulsions containing 100% LCT or 50%
      LCT/50% MCT on tumor necrosis factor (TNF) production by human mononuclear cells.
      STUDY DESIGN: This was a prospective study, in which 20 malnourished patients
      were randomly allocated to receive either 100% LCT or 50% LCT/50% MCT for > 30
      days. We measured TNF synthesis before initiation of TPN, as well as at 15 and 30
      days during TPN. SETTING: Departments of Medicine and Surgery, Patras University
      Medical School, Patras, Greece. PARTICIPANTS: Members of the staff of the
      Departments of Medicine and Surgery, Patras University Medical School. RESULTS:
      We found that TNF production was significantly (p < 0.01) elevated at 30 days in
      the LCT group, while no significant differences were detected in the LCT/MCT
      group. CONCLUSIONS: It is concluded that long-term TPN formulas, where LCT have
      been partially replaced by MCT, do not change TNF synthesis by peripheral blood
      mononuclear cells, and this may be beneficial in seriously ill, cachectic
      patients.

PMID- 8157853
TI  - Magnesium status in healthy free-living elderly Norwegians.
AB  - OBJECTIVE: Magnesium (Mg) status has previously not been properly assessed among
      healthy elderly subjects. METHODS: Thirty-six healthy elderly subjects
      participated. Their Mg status was assessed by serum Mg, basal urinary Mg output,
      and with a Mg loading test (30 mmol infused during 8 hours; urine sampled 24
      hours), and compared with 53 healthy younger subjects. Their dietary intake was
      assessed by a quantified food frequency questionnaire. Fourteen of the subjects
      received 300 mmol Mg to study the effect on Mg status. RESULTS: With the
      exception of vitamin D in women, average energy and nutrient intakes were
      adequate. All subjects had serum Mg levels within the reference value of the
      laboratory. Basal urinary Mg excretion was 3.3 +/- 1.1 mmol/day and 24-hour Mg
      retention after a Mg load was 28 +/- 16% compared to 6 +/- 11% in younger
      controls, suggesting Mg deficiency in the elderly. In the 14 subjects who
      received oral Mg supplementation there was a statistically significant increase
      in basal urinary Mg excretion and creatinine clearance, and decreases in Mg
      retention, serum Mg and serum creatinine. CONCLUSIONS: This study suggests that a
      significant subclinical Mg deficit, not detected by serum Mg, was present in many
      of these healthy elderly subjects. Mg supplementation improved Mg status and
      renal function.

PMID- 8157854
TI  - Asymptomatic environmental enteropathy among slum-dwelling infants.
AB  - OBJECTIVE: We documented asymptomatic environmental enteropathy, which may occur
      in low socioeconomic populations, and which is manifested by bacterial
      proliferation in the upper portions of the small bowel and by alterations in the
      digestive-absorptive capacity. DESIGN: Forty asymptomatic infants (< 1 year) of
      the Cidade Leonor slum in Sao Paulo, Brazil, were investigated for digestive
      absorptive function, bacterial proliferation in the small bowel lumen, and
      jejunal morphology. They were compared with a control group of 8 well-nourished
      children from economically sound families. RESULTS: Mean value of the D-xylose
      absorption test in the slum infants 21.0 +/- 10.0 mg%) was significantly lower
      than in controls (46.0 +/- 13.8 mg%) (p < 0.001). Colonic bacterial proliferation
      in the small bowel was identified in 25 (62.5%) of slum-dwelling infants. Grade
      II villous atrophy with inflammatory infiltration in the lamina propria was the
      most frequent alteration found. CONCLUSION: These data show that alterations in
      the microecology, function and morphology of the small intestine can occur even
      in the absence of diarrhea. Therefore, the absence of symptoms does not
      necessarily imply a healthy well-being among children living in a slum.

PMID- 8157855
TI  - Thiamin status of the elderly: dietary intake and thiamin pyrophosphate response.
AB  - OBJECTIVE: The present study was undertaken to investigate the relationship
      between thiamin intake and its biochemical status in 60 free-living (30 male, 30
      female) elderly subjects (> or = 65 years). DESIGN: Dietary intake was estimated
      using a 3-nonconsecutive-day food record. Biochemical status was assessed by
      measuring the stimulating effect of thiamin pyrophosphate (TPP) on transketolase
      activity (TPP effect) in hemolyzed erythrocytes, which is a functional test
      indicative of metabolic availability of thiamin. RESULTS: Average daily thiamin
      intake was above the recommended requirement (> 0.4 mg/1000 Kcal) for each
      gender; however, almost half of the total study population had TPP effect > 14%,
      suggesting thiamin deficiency. There was no correlation between thiamin intake
      and TPP effect. CONCLUSION: These findings raise questions about the reliability
      of dietary intake in assessing metabolic availability of thiamin in the elderly.

PMID- 8157856
TI  - Consequences on the newborn of chronic maternal consumption of coffee during
      gestation and lactation: a review.
AB  - The present review is devoted to effects on the newborn of maternal ingestion of
      caffeine during gestation and lactation. In rodents, caffeine is able to induce
      malformations, but usually at high doses never encountered in humans; indeed,
      when caffeine is administered in fractioned quantities during the day, as it is
      the case with human caffeine intake, caffeine is no longer a teratogen in
      rodents. Caffeine ingested during gestation induces a dose-dependent decrease in
      body weight, but only for large doses (> 7 cups/day of coffee), whereas it has no
      effect at moderate doses. Maternal caffeine consumption during gestation affects
      hematologic parameters in both rat and human infants and induces long-term
      effects on sleep, locomotion, learning abilities, emotivity and anxiety in rodent
      offspring, whereas in humans, more studies are needed to determine the
      consequences of early caffeine exposure on behavior. Investigators do not agree
      on the quantities of the methylxanthine found in breast milk, but caffeine does
      not change breast milk composition, and rather, stimulates milk production. We
      conclude in this review that maternal caffeine consumption in moderate amounts
      during gestation and lactation has no measurable consequences on the fetus and
      newborn infant. Pregnant mothers, however, should be advised to consume coffee
      and caffeinated beverages in moderation, especially because of the prolonged half
      life of caffeine both during the last trimester of pregnancy and in the newborn
      infant.

PMID- 8157858
TI  - Influence of smoking on folate intake and blood folate concentrations in a group
      of elderly Spanish men.
AB  - OBJECTIVE: To investigate the relationship between smoking habits and folate
      status in a group of elderly Spanish men. DESIGN: We studied folate intake, serum
      and erythrocyte folate concentrations, hematological and biochemical data in 72
      elderly males (comparing 24 smokers data with 44 nonsmokers ones). RESULTS:
      Percentage deficiencies for folate intake, serum and erythrocyte levels were
      higher in smokers. Serum folate levels were significantly higher in nonsmokers.
      Smokers had higher mean corpuscular volume than did nonsmokers. CONCLUSIONS:
      Smoking could be harmful to the intake and folate status. For smokers who will
      not give up the habit, improved dietary intake or a folate supplement is
      advisable.

PMID- 8157857
TI  - Zinc supplementation alters thyroid hormone metabolism in disabled patients with
      zinc deficiency.
AB  - OBJECTIVE: We examined zinc (Zn) status in relation to thyroid function in
      disabled persons, because the association between Zn deficiency and thyroid
      function remains controversial. METHODS: After measuring serum free 3,5,3'
      triiodothyronine (T3) and free thyroxine (T4) in 134 persons, TSH-releasing
      hormone (TRH) injection test and estimation of Zn status were conducted in
      persons with low free T3. RESULTS: Thirteen had low levels of serum free T3 and
      normal T4. Patients with elevated levels of serum 3,3',5'-triiodothyronine (rT3)
      showed an enhanced reaction of serum thyrotropin (TSH) after TRH injection. Nine
      of 13 patients had mild to moderate Zn deficiency evaluated by body Zn clearance
      and increased urinary Zn excretion. After oral supplementation of Zn sulphate (4
      10 mg/kg body weight) for 12 months, levels of serum free T3 and T3 normalized,
      serum rT3 decreased, and the TRH-induced TSH reaction normalized. Serum selenium
      concentration (Type 1 T4 deionidase contains selenium in the rat) was unchanged
      by Zn supplementation. CONCLUSION: Zn may play a role in thyroid hormone
      metabolism in low T3 patients and may in part contribute to conversion of T4 to
      T3 in humans.

PMID- 8157859
TI  - Effects of high sugar diets on renal fluid, electrolyte and mineral handling in
      rats: relationship to blood pressure.
AB  - OBJECTIVE: We examined whether sugar-induced systolic blood pressure (SBP)
      elevations in rats may develop, in part, through a mechanism common to salt
      induced hypertension, i.e., renal retention of water and salt. DESIGN:
      Spontaneously hypertensive rats (SHR) ate four diets: two high (> 50% of
      calories) and two low (< 12% of calories) in sugar (sucrose). SBP, various
      urinary parameters, and the renal angiotensin and prostaglandin systems were
      assessed. RESULTS: SHR consuming diets high in sugar showed significantly
      decreased urinary volume and excretion of electrolytes, which coincided with
      increasing SBP. When low sugar diets replaced high sugar diets, SBP and urinary
      parameters rapidly returned to baseline. SHR received captopril while consuming
      high sugar diets, and both SBP and urinary parameters assumed baseline values,
      comparable to ones seen in SHR consuming low sugar diets. A direct angiotensin II
      receptor antagonist (DuPont 753) did not influence SBP. However, we found
      decreased PGE2 excretion in SHR consuming excess sugar. CONCLUSIONS: Salt and
      water retention occur early during sugar-induced hypertension due to reduced
      renal excretion, consistent with some part in the pathogenesis. The effects of
      high sugar diets on SBP were not due to angiotensin II inhibition, however,
      decreased availability of vasodilatory prostaglandins may play a role in the
      renal events and sugar-induced hypertension in SHR.

PMID- 8157860
TI  - High concentrations of vitamin A esters circulate primarily as retinyl stearate
      and are stored primarily as retinyl palmitate in ferret tissues.
AB  - OBJECTIVE AND METHODOLOGY: We determined the kinds and amounts of vitamin A
      compounds (retinol and various retinyl esters) circulating in serum and stored in
      liver and other selected tissues of ferrets, using high-performance liquid
      chromatography. RESULTS: The concentration of total retinyl esters in serum (43
      +/- 1 mumol/L, mean +/- SEM) was 25 times greater than that of retinol (1.7 +/-
      0.2 mumol/L). In serum, 56% of retinyl esters was retinyl stearate, 33% was
      retinyl palmitate, and 5% was retinyl oleate. In contrast, in liver, vitamin A
      was stored primarily as retinyl palmitate (51%); smaller amounts of retinyl
      oleate (19%) and retinyl stearate (16%) were found. In kidneys, adrenals, small
      intestine, adipose tissue, skin, stomach, and eyes, retinyl palmitate was also
      the predominant retinyl ester, followed by retinyl stearate. In colon, lungs, and
      bladder, equal amounts of retinyl palmitate and retinyl stearate were observed.
      Other retinyl esters present in smaller amounts in most of these tissues were
      retinyl oleate, retinyl linoleate and/or -myristate, retinyl heptadecanoate,
      retinyl arachidonate, and retinyl laurate. CONCLUSIONS: Thus, the primary form of
      vitamin A that circulates in the blood of ferrets is retinyl stearate, whereas
      the primary storage form of the vitamin in tissues is retinyl palmitate.
      Concentrations of total vitamin A in ferret serum and other tissues were 3-73
      times greater than those reported for their corresponding human tissues.

PMID- 8157861
TI  - Assessment of vitamin B6 status of strength and speedpower athletes.
AB  - OBJECTIVE: The investigation was designed to obtain information concerning the
      vitamin B6 status in high-performance athletes. SUBJECTS: Fifty-seven strength
      and speedpower athletes were available for examination. METHODS: Vitamin B6
      status was determined by a 7-day weighed food record, enzyme activity (alpha
      EGOT) measurement, whole blood concentrations (Saccharomyces carlsbergenisis and
      4-pyridoxinic acid (4-PA) excretion (high-pressure liquid chromatography).
      RESULTS: The absolute vitamin B6 intake in > 30% of the athletes was below the
      German recommended dietary allowance (GRDA) and, in relation to the protein
      intake (GRDA 0.20 mg vitamin B6/g protein), > 60% of the athletes had values
      below the GRDA. More than 90% of the athletes did not attain the reference value
      (0.88 nmol/mL) for untrained individuals in vitamin B6 whole blood concentration,
      and only a few athletes (< 5%) had alpha-EGOT values above the reference value of
      alpha-EGOT > 1.50). The 4-PA excretion was below the reference value of > 2.73
      mumol/g creatinine in 18% of all athletes examined. CONCLUSIONS: Vitamin B6
      status can be quantified using the weighed food record, microbiological whole
      blood determination, and 4-PA excretion; however, limits of the individual
      methods must be taken into account. Vitamin B6 supply of the athletes still
      cannot be definitively assessed because there are no generally valid reference
      values.

PMID- 8157862
TI  - Bioavailability of selenium from raw and cooked ground beef assessed in selenium
      deficient Fischer rats.
AB  - OBJECTIVE: The literature on the bioavailability of selenium (Se) from meats,
      especially beef, is meager, and that which existed when this research began
      suggested that Se was not highly bioavailable. In addition, much of the
      analytical values for Se in beef predated the Food and Drug Administration's 1973
      approval of Se as an additive to feeds and mineral premixes of livestock. DESIGN:
      One hundred and thirty-six weanling female Fischer 344 rats were divided into two
      dietary groups: the selenium deficient group in which animals were fed a torula
      yeast (TY) basal diet which contained 0.008 mg/kg Se and the control group in
      which animals were fed the TY diet to which was added 0.10 mg/kg Se as sodium
      selenite. RESULTS: After 6 weeks of dietary treatment liver glutathione
      peroxidase (GSHPx) activity had fallen in the Se-deficient rats to 2.4% of that
      of control rats. At this time (week 6) rats from the Se-deficient TY diet were
      refed diets containing 0.10 mg/kg Se as selenite, selenate, raw or cooked ground
      beef that had been freeze-dried. During the Se-repletion period rats were
      sacrificed at weeks 1, 3, 5 and 8. Liver GSHPx activity and total Se levels in
      liver and muscle tissue were the criteria of Se bioavailability. After 8 weeks of
      Se resupplementation the recovery of liver GSHPx activity compared to the control
      animals (set at 100%) were selenite (98%, p > 0.05), selenate (117%, p < 0.05),
      raw beef (127%, p < 0.05) and cooked ground beef (139%, p < 0.05). Total Se in
      both liver and muscle tissue reflected the liver GSHPx activity with the total Se
      concentration in tissues being highest for cooked beef. CONCLUSION: The data
      suggest that bioavailability of Se from ground beef is greater than that from
      either selenite or selenate.

PMID- 8157863
TI  - Toxicity of diethanolamine. 1. Drinking water and topical application exposures
      in F344 rats.
AB  - Toxicology studies of diethanolamine were conducted in male and female F344 rats
      for 13 weeks' duration to characterize and compare effects of exposure in the
      drinking water with those caused by topical application. Doses of diethanolamine
      ranged from 160 to 5000 ppm in the drinking water study (equivalent to daily
      doses of 25-440 mg kg-1 in males and 15-240 mg kg-1 in females) and from 32 to
      500 mg kg-1 in the topical application study. Dose-dependent toxic effects due to
      exposure to diethanolamine included hematological changes (a poorly regenerative,
      microcytic anemia), as well as toxic responses in the kidney (increased weight,
      tubular necrosis, decreased renal function, and/or tubular mineralization), brain
      and spinal cord (demyelination), testis (degeneration of the seminiferous
      tubules) and skin (site of application: ulceration, inflammation, hyperkeratosis
      and acanthosis). A no-observed-adverse-effect level was not achieved for
      hematological changes, nephropathy or hyperkeratosis of the skin. Differences in
      dose-response between the drinking water and topical application exposures were
      attributed largely to the limited dermal absorption of this chemical.

PMID- 8157864
TI  - Toxicity of diethanolamine. 2. Drinking water and topical application exposures
      in B6C3F1 mice.
AB  - Toxicology studies of diethanolamine were conducted in male and female B6C3F1
      mice to characterize and compare effects of exposure in the drinking water with
      those caused by topical application and to compare responses in mice to those
      observed in rats. Each study consisted of five dose groups plus controls and the
      size of each group was 10 animals per sex. Doses of diethanolamine ranged from
      630 to 10,000 ppm in the drinking water study (approximately equivalent to daily
      doses of 100-1700 mg kg-1 in males and 140-1100 mg kg-1 in females) and from 80
      to 1250 mg kg-1 in the topical application study. Exposure to diethanolamine
      caused dose-dependent toxic effects in the liver (hepatocellular cytological
      alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in
      males), heart (cardiac myocyte degeneration) and skin (site of application:
      ulceration, inflammation, hyperkeratosis, and acanthosis). Cytological
      alterations in the liver consisted of multiple hepatocyte changes, including
      enlarged cells that were frequently multinucleated, increased nuclear
      pleomorphism, increased eosinophilia and disruption of hepatic cords. A no
      observed-adverse-effect level (NOAEL) was not achieved for hepatocellular
      cytological alterations or for acanthosis in the skin.

PMID- 8157865
TI  - Effect of Tordon 2,4-D 64/240 triethanolamine BR on the energy metabolism of rat
      liver mitochondria.
AB  - Tordon herbicide, which is a mixture of 4-amino-3,5,6-trichloropicolinic acid
      (picloram) and 2,4-dichlorophenoxyacetic acid (2,4-D), depresses the
      phosphorylation efficiency of the rat liver mitochondria, as inferred from the
      decrease of the respiratory control coefficient and the ADP/O ratios when NAD(+)
      dependent substrates were used; NADH oxidase and NADH cytochrome c reductase were
      also inhibited, without any effect on the other enzymatic complexes of the
      respiratory chain. Tordon (66.2 nmol picloram + 270 nmol 2,4-D mg-1 protein)
      affected the amplitude of swelling induced by glutamate, succinate, (N,N,N',N'
      tetramethyl-p-phenyldiamine + sodium ascorbate and ATP. These results
      characterize an interaction of Tordon with complex I of the respiratory chain and
      also a partial collapse of the proton motive force of the mitochondrial inner
      membrane without affecting its elasticity.

PMID- 8157866
TI  - Cardioteratogenic dose of ethanol reduces both lactic dehydrogenase and succinic
      dehydrogenase activity in the bulbar ridges of the embryonic chick heart.
AB  - It has been established previously that the chick embryo is an appropriate model
      for studying the pathogenesis of ethanol-induced ventricular septal defect and
      that the growth and fusion of the proximal bulbar ridges are critical to
      ventricular septation within the embryonic heart. To determine whether enzyme
      activity was altered significantly in bulbar ridges in response to a
      cardioteratogenic dose of ethanol, we injected 0.32 ml of 50% ethanol in chick
      Ringer's saline (CRS) into the air cells of 3-day-old chick embryos (72-84 h
      incubation, Hamburger-Hamilton stages 18-19, Dekalb Delta strain). Embryos were
      harvested 48-60 h after treatment (stages 26-27). Hearts were removed, frozen and
      sectioned, and the tissues were processed for enzyme histochemical demonstrations
      of lactic and succinic dehydrogenase. Twelve ethanol-treated embryos and 12 CRS
      treated controls were compared for lactic dehydrogenase (LDH) levels. Fourteen
      ethanol-treated embryos and 14 controls were compared for succinic dehydrogenase
      (SDH) levels. Formazan deposits were quantified by means of computer-assisted
      microdensitometry. Our results showed that ethanol decreased the mean LDH
      activity level by 36.3% (P = 0.005) and the mean SDH level by 40.8% (P < 0.02).
      Furthermore, ethanol significantly reduced LDH activity in 41.7% of the matched
      embryo pairs and significantly reduced SDH activity in 57.1% of the matched
      embryo pairs. Although some investigators have proposed that a disturbance in
      neural crest cell migration plays a major role in the pathogenesis of ethanol
      induced cardiac malformations, this study provides evidence that the bulbar
      ridges of the embryonic heart are also potential target tissues for ethanol.

PMID- 8157867
TI  - Cardioteratogenic dose of ethanol in the chick embryo results in albumin ethanol
      concentrations comparable to human blood alcohol levels.
AB  - Three-day-old chick embryos (Hamburger-Hamilton stages 18-19) were exposed to a
      dose of ethyl alcohol (0.32 ml of 50% ethanol) that causes cardiac malformations
      in 96.6% of the animals. Ethanol was administered into the air sac after 72-80 h
      of incubation. Samples of albumin at the opposite pole of the egg were drawn 0-50
      h after treatment and quantitated for ethanol concentration with capillary gas
      liquid chromatography. Ethanol concentrations in the albumin increased
      significantly (P < 0.05) at 2, 5 and 15 h after injection of ethanol, reached a
      maximum mean ethanol concentration at 20 h (217.3 +/- 23.5 mg dl-1), decreased
      significantly at 30 h to 175.4 +/- 27.5 mg dl-1, then increased again and
      stabilized at 40-50 h. Individual sample concentrations ranged from 0 mg dl-1 (at
      0.5-2 h) to 286.5 mg dl-1 at 40 h. Ethanol concentrations in the albumin were
      comparable to human blood alcohol levels during intoxication (> 150 mg dl-1). Our
      results suggest that a potent cardioteratogenic dose of ethanol in the chick
      embryo is reasonable in terms of potential human embryo exposure.

PMID- 8157868
TI  - Testicular lesions by chronic administration of cocaine in rats.
AB  - Although cocaine is a common drug of abuse, its effects on the testicular
      structure have not been studied in depth. We report here the testicular lesions
      produced by chronic cocaine administration to rats. Twenty-eight male Wistar rats
      weighing 225-250 g were used throughout. Fourteen of them (controls) were
      injected i.p. with saline solution and the remaining 14 received 30 mg kg-1 day-1
      i.p. of aqueous cocaine hydrochloride solution. Animals from both groups were
      sacrificed at variable times: 7, 15, 30, 45, 60, 75 and 90 days of treatment.
      Histopathological examination of the testes showed initial alterations at day 15:
      capillary dilatation; interstitial oedema with lipoid drops due to incipient
      necrosis of interstitial cells; and necrosis of the cells of the seminiferous
      tubules. Lesions progressed until 90 days of treatment, showing atrophic and
      necrotic cells and terminal tubule fibrosis. At this time, the testes were found
      to be diminished in size. The seminiferous tubules were shrunken, of small
      diameter and contained necrotic spermatogenic cells and fibrosis. These lesions
      may produce testosterone diminution and thus sterility due to the disappearance
      of spermatogenesis.

PMID- 8157869
TI  - Isoflurane increases the anaerobic metabolites of halothane.
AB  - The effect of isoflurane on the anaerobic metabolism of halothane to
      chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE) was studied with
      microsomes of guinea pig liver by gas chromatography. The reaction mixture used
      to measure the end products of anaerobic metabolism consisted of a microsomal
      suspension, 3 mM NADPH, halothane and isoflurane (except in control groups) in
      0.1 M potassium phosphate buffer solution (pH 7.4). The Km values for CDE
      formation were 601.61 +/- 266.91, 254.22 +/- 86.58, 257.92 +/- 129.11, 268.55 +/-
      125.66 and 319.22 +/- 86.76 microM (mean +/- SD, n = 5) at 0 mM (0%), 0.12 mM
      (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM (2.59%) isoflurane,
      respectively. The Km values for CTE formation were 1204.74 +/- 551.64, 553.75 +/-
      177.89, 521.14 +/- 249.77, 560.67 +/- 229.61 and 711.05 +/- 317.13 microM (n = 5)
      at 0 mM (0%), 0.12 mM (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM
      (2.59%) isoflurane, respectively. In contrast, the Vmax values for CDE and CTE
      formation at these isoflurane concentrations were not significantly different
      than in the control groups. In this study the production of CDE and CTE was
      significantly (P < 0.05) increased by isoflurane, at concentrations up to 0.58 mM
      (1.30%).

PMID- 8157870
TI  - Coronary vessel alterations following chronic carbon monoxide exposure in the
      adult rat.
AB  - Adult male rats were exposed to 500 ppm CO continuously for 30 days, while litter
      mate controls remained in room air (AIR). Heart weight-to-body weight ratio and
      hematocrit were increased significantly. Right ventricle (RV) free wall thickness
      was increased significantly as was right to left heart diameter and average heart
      diameter. Cross-sectional areas of the left ventricle (LV) free wall,
      interventricular septum (S) and RV midway between the apex and base were
      increased significantly. Morphometric analysis of the CO-exposed and AIR hearts
      revealed no significant differences in the number of small (27-114 microns) or
      larger (> 114 microns) blood vessels in any region; however, there was a trend
      towards an increased number of the smaller vessels, both arterioles and venules,
      in the CO-exposed rats. The larger arteries in the S and RV were significantly
      larger in the CO-exposed rats. There was a significant overall effect of CO on
      larger artery diameter across all heart regions, consistent with the appearance
      of heart radiographs taken. There were no differences in the diameter of the
      small vessels in any region of the heart between the CO-exposed and AIR rats. The
      vessel cross-sectional area of the larger vessels tended to be increased in all
      regions of the heart. The cross-sectional area of the large arteries in the LV
      was increased significantly. Arterial wall thickness was decreased significantly
      in RV and there was a significant overall effect of CO in decreasing wall
      thickness and the ratio of wall thickness-to-vessel luminal diameter in these
      vessels. No vascular pathology was observed. The results of this study suggest
      changes in coronary vessel architecture during chronic CO-induced cardiac
      hypertrophy and are consistent with earlier hemodynamic and morphometric studies
      of CO-exposed hearts.

PMID- 8157871
TI  - Validation of an improved nose-only exposure system for rodents.
AB  - Several types and modifications of nose-only inhalation chambers for exposing
      rodents are described. The improvement of this 'flow-past' -like nose-only
      exposure system is that it is modular, i.e. it can be used for acute studies with
      a maximum of 20 rodents (one segment) or for chronic inhalation studies with 100
      (or more) rodents per chamber with five (or more) segments. Another goal was to
      design a nose-only exposure system that provides maximal computer support and
      automatization, as well as robust aerosol collection conditions. The evaluation
      of the five-segment chamber, charged with 98 rats, revealed that a flow rate of
      0.75 l air min-1 or approximately 2.5 times the rat minute ventilation volume per
      exposure port is sufficient to provide homogeneous temporal and spatial exposure
      conditions. Also, the aerosol size distribution was constant throughout the
      chamber. Experimental data suggest that computer-controlled sampling of the test
      atmosphere up to ca. 6 l air min-1 did not alter the flow dynamics of the
      exposure system. The nose-only inhalation chamber developed is suitable for short
      term and long-term inhalation toxicity studies using small laboratory rodents
      with minimal consumption of test compound.

PMID- 8157872
TI  - Correlation between concentrations of n-hexane and toluene in exhaled and
      environmental air in an occupationally exposed population.
AB  - We determined the correlations between the concentrations of n-hexane and toluene
      in exhaled and environmental air in the shoe manufacturing industry. Data were
      collected in 1988 and in 1992 from a total of 265 subjects. Environmental air
      samples were collected with personal diffusive samplers by adsorption on
      activated charcoal during exposure and from end-expired air (alveolar air) on
      cartridges of activated charcoal after exposure. Both compounds were desorbed
      with carbon disulphide and analysed by gas chromatography. Linear regression
      analyses showed a good correlation between environmental and end-expired air
      concentrations (r = 0.82 for n-hexane and r = 0.81 for toluene). These
      correlations allowed us to calculate the concentrations in expired air
      corresponding to current environmental limit values. The calculated
      concentrations in end-expired air that correspond to current environmental
      threshold limit values of 176 mg m-3 for n-hexane and 377 mg m-3 for toluene are
      28 mg m-3 (95% confidence limit, 27-29 mg m-3) and 40 mg m-3 (95% confidence
      limit, 39-41 mg m-3), respectively. Similar correlations were found when the data
      from the two study periods were analysed separately.

PMID- 8157873
TI  - Oxadiazon.

PMID- 8157874
TI  - Concerning the paper 'Evaluation of the dermal carcinogenicity of lubricant base
      oils by the mouse skin painting bioassay and other proposed methods' by K. L.
      Chasey and R. H. McKee, J. Appl. Toxicol. 13(1), 57-65 (1993)

PMID- 8157875
TI  - Spousal caregivers' burden: impact of care recipient health problems and mental
      status.
AB  - 1. Caregiver burden is a three-dimensional concept. It reflects the impact of
      caregiving on interpersonal relationships; expressions of caregiver anxiety; and
      the personal impact of the caregiver role. 2. In the study presented, mental
      impairment had the most significant negative impact on caregiver burden overall,
      as well as on each of the three components of burden--regardless of an impaired
      elder's physical problems. 3. Nursing strategies to improve the care of frail
      elders and their caregivers include the development and implementation of a
      sensitive discharge assessment and plan; articulation between the hospital-based
      and community-based nurses; and assessment of the caregiver-care receiver dyad.

PMID- 8157876
TI  - Extended care and nursing home staff attitudes toward restraints. Moderately
      positive attitudes exist.
AB  - 1. The average score on the Restraint Questionnaire for Staff indicated that the
      extended care and nursing home staff members in the study presented had
      moderately positive attitudes toward using restraints. 2. There were no
      significant differences in attitude scores based on gender, position, education,
      or clinical experience. 3. Collaborating with another professional, especially a
      physician, was related to a more positive attitude toward restraints; this effect
      approached statistical significance. 4. Sixty-five percent of the staff could
      offer no alternatives to restraining a patient; for those who could offer an
      alternative, increasing staff size was cited most frequently.

PMID- 8157877
TI  - Student/staff collaboration: a pilot bowel management program.
AB  - 1. Poor bowel elimination and constipation plague many individuals with advanced
      age. Moreover, the use of laxatives as the panacea for these concerns is far too
      common. 2. A successful bowel management program was implemented at the study
      facility through the collaborative efforts of baccalaureate nursing students and
      nursing home staff members. 3. The bowel management protocol involved increasing
      the amount of fiber, fluids, and exercise for each resident in the study. 4. The
      program demonstrated a definite decrease in the number of laxatives used by the
      subjects as well as an increase in the number of spontaneous bowel movements.

PMID- 8157878
TI  - Screening for polypharmacy in a nursing home care unit.

PMID- 8157879
TI  - The physical and mental health of women caregivers of older adults.

PMID- 8157880
TI  - Quality in nursing home care.

PMID- 8157881
TI  - Alzheimer's and related disorders: loneliness, depression, and social support of
      spousal caregivers.
AB  - 1. Meeting the myriad of emotional and social needs of caregivers for spouses
      with Alzheimer's disease (AD) will increasingly challenge nurses and the health
      care system. 2. Whether the person with AD remains at home or is
      institutionalized, spousal caregivers are at risk for loneliness and decreased
      social support. 3. Research studies have consistently found spousal caregivers to
      suffer from depression. 4. A comprehensive assessment of the caregiver and the
      care recipient may help the clinician identify aspects of the caregiving
      situation that are amenable to change.

PMID- 8157882
TI  - [Essential thrombocythemia and pregnancy].

PMID- 8157883
TI  - [Where in the world is perinatal medicine going?].

PMID- 8157884
TI  - [Recommendations on the practice of obstetrical analgesia. The Group for
      Recommendations on Obstetrical Analgesia].

PMID- 8157885
TI  - [The biological activity of luteinizing hormone (LH)].
AB  - In vitro bioassay (BIO) is a very specific and sensitive method for determining
      levels of luteinizing hormone (LH). It provides a means of evaluating the values
      obtained with routine radioimmunoassays (RIA). Serum levels with bioassay are
      higher than those obtained with radioimmunoassay. The LH BIO/LH RIA ratio
      measures the difference between the two methods and gives a means of evaluating
      the quality of the LH secreted. The LH BIO/LH RIA ratio is significantly higher
      at the summit than at the nadir of the LH serum pulses. This ratio also increases
      after administration of GnRH. The differences in the quality of the LH can be
      explained by micro-heterogenicity. Immunofluorometric assay of LH (LH FIA) is
      much more sensitive than either the LH BIO or the LH RIA assays. Unlike the LH
      BIO/LH RIA ratio, the LH BIO/LH FIA ratio remains unchanged during LH pulses and
      after administration of GnRH. This difference can be explained by the lack of
      sensitivity but also by the lack of specificity of the LH RIA. LH RIA is not
      reliable when the serum levels of LH are low. However, RIA is valid when the
      serum levels of LH are increased as occurs in polycystic ovary syndromes.

PMID- 8157886
TI  - [Does medically-assisted procreation cause sterility? Apropos of unexplained
      sterility].
AB  - The authors emphasize the concept of in vitro fecundation as an intrusion. The
      intruding agents include the desire for a child itself, the family and the
      physician. This new concept throws light on the questions raised by unexplained
      infertility. The authors conclude that the effectiveness of therapeutic
      strategies derived from the model of tubal destruction is doubtful.

PMID- 8157887
TI  - [Typing of human papillomaviruses in intra-epithelial malpighian lesions of the
      cervix uteri: correlation with cytohistologic grade and progression of the
      lesions].
AB  - The clinical course of condylomas of the cervix, and more generally of all
      cervical dysplasias whether associated with koilocytosis or not, remains
      unpredictable. Based on a series of earlier publications, we undertook a routine
      typing for human papillomaviruses in intraepithelial malpighian lesions of the
      cervix. We examined the real usefulness of such typing to determine prognosis of
      the lesions and correct clinical management. We determined the correlations
      between human papillomaviruses, as detected by the in situ hybridization method,
      with the histological grade of 125 cervical lesions (in 106 patients) and the
      clinical course (mean follow-up = 24 months) in 56% of them. Viruses 16/18 and/or
      31/33/55, considered to be potential oncogenes, predominated, whatever the grade,
      in in situ hybridization positive intraepithelial malpighian lesions (57 out of
      59 cases; 97%). In the follow-up cases, there was no difference in the clinical
      course of the lesions in terms of grade (simple condyloma mild or moderate
      dysplasia) based on the hybridization results (detection and typing). These
      findings suggest that routine viral typing cannot be proposed to determine the
      therapeutic attitude (abstention, destruction) for the management of
      intraepithelial lesions of the cervix.

PMID- 8157888
TI  - [The possible endometrial risk of ovarian stimulation. Apropos of 3 cases].
AB  - Three cases of adenomatous hyperplasia of the endometrium--one of them
      degenerated--have been reported in young women provided with ovulation
      stimulation. The association between these hormonal therapies and the
      adenocarcinoma or its antecedents signs, is particularly disturbing. However,
      it's difficult to establish a relationship between cause and effect. Indeed the
      women who suffer from an ovarian sterility are a group exposed to a cancer of the
      endometrium independently of any other iatrogenic agent. The method of detection
      is yet to be found, as is the mode of conduct which can reconcile the risk of a
      carcinoma and the desire of pregnancy.

PMID- 8157889
TI  - [A new therapeutic strategy using a ofloxacin-amoxicillin-clavulanic acid
      combination in the treatment of upper gynecologic infections. Apropos of 123
      cases].
AB  - OBJECTIVE: To evaluate a new antibiotic strategy with a combination of ofloxacin
      + co-amoxiclav in the treatment of pelvic infectious diseases. DESIGN: An open
      non-comparative multicentre (10) study. SUBJECTS: 123 patients (118 salpingitis
      and 5 endometritis) were included clinical, laparoscopic and bacteriological
      assessments were performed before treatment and a laparoscopic control was done
      in 35% of cases. Among positive bacteriological samples before treatment 48.7% C.
      trachomatis were isolated; 56.1% of salpingitis were considered as severe (COGIT
      score > 6). TREATMENT: Patients received at entry oral ofloxacin 200 mg bid in
      combination with parenteral co-amoxiclav 2 to 4 g following by oral route. Total
      duration of treatment was 21 days. RESULTS: With respectively 97.2% and 91.6%
      satisfactory clinical and bacteriological results, this combination should take a
      major place in the treatment of pelvic infectious diseases.

PMID- 8157890
TI  - [The association of genito-urinary prolapse and bladder lithiasis].
AB  - Two cases of third degree tri-segmentary prolapse were associated with bladder
      calculi. Two cm calculi in the first case and a unique 4 x 5 cm calculus in the
      second made diagnosis difficult and raised the question of the choice of therapy.

PMID- 8157891
TI  - [Changes in the utero-placental and fetal cerebral circulations induced by
      nicotine in the ovine fetus].
AB  - Foetal and maternal circulations were studied in 5 gestating sheep given an intra
      muscular nicotine injection (10 mg) daily for 65 days beginning on the 60th day
      of gestation. Six control sheep and 5 others given a placebo injection comprised
      the control group. Placental (Rp), cerebral (Rc) and uterine (Ru) vascular
      resistances were measured by Doppler at the following sites: umbilical arteries,
      foetal cerebral arteries, uterine arteries. Measurements were taken at 80, 100
      and 130 days of gestation. The Doppler resistance indices were comparable in the
      control and placebo group. The cerebral Doppler resistance indices were
      comparable in the three groups at 80 and 100 days, but there was a significant
      increase at day 130 in the nicotine group (p < 0.01). This increase was in favour
      of reduced cerebral perfusion. The umbilical indices were slightly higher at 80
      and 130 days in the nicotine group (p < 0.01). The cerebro-placental ratio
      (Rc/Rp) remained unchanged in the controls, but increased significantly in the
      nicotine fetuses (p < 0.05) confirming a redistribution of the fetal blood flow
      away from the brain. There was no significant difference in the uterine
      resistances at 80 and 100 days in the nicotine group (p < 0.01), but they
      increase between 100 and 130 days. In the control and placebo groups, delivery
      occurred at normal gestation dates. In these two groups, two lambs (10%) were
      stillborn. In the nicotine group, premature delivery occurred in two sheep and 8
      of the 13 lambs (63%) were stillborn.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8157892
TI  - [The value of early morphologic ultrasonography for the detection of chromosome
      anomalies].
AB  - OBJECTIVES: To demonstrate the benefit, in terms of improved antenatal screening,
      in particular for 21-trisomy, to be expected from the introduction of routine
      vaginal morphologic echography during the first trimester of pregnancy. This work
      was conducted by the Department of Gynaecology-Obstetrics of the French Red Cross
      Teaching Hospital in Bois-Guillaume, France. SUBJECT: Over a 20 month period, 307
      consultating women underwent routine endovaginal echography between the 10th and
      13th week of amenorrhoea. The exploration was proposed to detect small
      retrocervical hydromas as a signal for further cytogenetic tests. RESULTS: Five
      hygromas were discovered and led to the diagnosis of 4 cases of 21-trisomy, the
      fifth pregnancy ended with spontaneous abortion. The 12th week appeared as the
      most favourable time for routine examination. CONCLUSIONS: This non-invasive
      method, routinely performed in all women, improves the yield of screening for 21
      trisomy and allows a better means of indicating cytogenetic tests.

PMID- 8157893
TI  - [The estimation of fetal weight by measurement of the adipose tissue of the
      extremities. Use in the diagnosis of hypotrophy].
AB  - OBJECTIVE: To investigate the accuracy of small for age fetuses diagnosis by a
      new method of fetal weight estimation, in comparison with some others models. A
      retrospective study. SUBJECTS AND METHODS: From a 232 fetuses population, whom
      age is known, ultrasound measurement have been performed (BPD, TBD, FL, AC and
      thigh circumference). Three physicians collaborated to data collection. All
      measurement have been done within a 3 days duration between measuring and birth
      in order to compare actual and calculated weight. There are 39 small fetuses
      coming from 10th percentile (17.5%), between then 24 from 5th percentile.
      RESULTS: Positive predictive value (PPV) of small for age diagnosis (from 10th P)
      by our model is 74% with a 74% sensibility and a 94% specificity. With Warsof
      estimation model, the PPV is only 47% with a 71% sensibility and a 83%
      specificity (p = 0.001). COMMENTS: Limbs subcutaneous fat ultrasound measurement
      improve considerably fetal weight estimation quality (mean error = 6% vs 10% for
      most of the classical models) and, as an extension, small for age fetuses
      diagnosis. The cutaneous and subcutaneous circumferences, between which is
      situated fat tissue have a better individual correlation to actual weight than
      abdominal circumference, usually considered as the best trophicity parameter.
      CONCLUSION: High positive predictive value show long term predictive detection
      possibility. It appears that this diagnosis could be done earlier with a better
      accuracy that the classical ultrasound biometry.

PMID- 8157894
TI  - [The difficulty of prenatal diagnosis of Kniest's disease. Apropos of a case
      simulating congenital spondylo-epiphyseal dysplasia].
AB  - The second antenatal diagnosis of Kniest's syndrome is described in this report.
      This skeletal dysplasia involving disproportional dwarfism and a flat facies is
      compatible with life and normal intelligence. The authors describe the observed
      sonographic imagery and emphasize the important role of ultrasonography for
      antenatal evaluation of the prognosis of the skeletal dysplasias. The main
      differential diagnosis is spondylo-epiphyseal dysplasia congenita.

PMID- 8157895
TI  - [Bilateral renal agenesis or Potter's sequence. A case of recurrent bilateral
      renal agenesis].
AB  - Bilateral renal agenesis (Potter's sequence) is usually a sporadic occurrence.
      Recurrence in the same family is rare. A family study of bilateral and unilateral
      renal agenesis was undertaken in three cases of renal agenesis in the same
      family. The grand-father and the father have a unilateral renal agenesis and his
      two stillborn infants had a Potter's syndrome. The author considered the familial
      nature of congenital absence of the kidneys and the relationship between
      hereditary bilateral renal agenesis and unilateral renal agenesis.

PMID- 8157896
TI  - [Early prenatal diagnosis of asymmetric cephalothoracopagus twins].
AB  - The authors report on one case of cephalothoracopagus Janiceps conjoined twins
      discovered by echography at 18 weeks' gestation. Conjoined twins have been said
      to occur with a frequency of 1/50,000 to 1/100,000 deliveries. The incidence of
      the cephalothoracopagus variety is one in three million births or one in 58
      conjoined twins. Three different mechanisms that may have played a role in the
      abnormal development of these twins are discussed. The risk that the condition
      recurs in a subsequent pregnancy are to be considered negligible.

PMID- 8157897
TI  - [Fine needle biopsy of sub-clinical breast lesions under ultrasonographic
      control].
AB  - Fine needle aspiration under ultrasonographic control fo non-palpable lesions has
      the advantage of being simple and non-traumatic for the patient. It is accessible
      to all radiologists equipped with a 7.5 MHz probe. The success of this method
      rests upon: excellent mammo-ultrasonographic correlation of the lesions under
      visual control with the patient in a mammographic position; use of a syringe with
      a self-locking plunger linked by a rubber tube to the aspiration needle; rinsing
      of the needle with a fixative (Carbowax) which will be submitted to
      centrifugation in the laboratory. The low cost of this method combined with is
      excellent results (4.5% unsatisfactory samples for lesions larger than 5 mm; 8%
      for lesions from 0 to 5 mm) make it an outstanding technique. Only for isolated
      clusters of microcalcification should samples by stereotaxy by preferred to it.
      Only in cases of unsatisfactory results should biopsy be preferred.

PMID- 8157898
TI  - [Acardiac twins].
AB  - An acardiac twin in a multiple pregnancy initially develops normally and is a
      specific complication of monozygous multiple pregnancies. Development results
      from arterio-arterial and veno-venous anastomoses leading to predominance of one
      of the twins. The haemodynamic abnormalities in the dominated twin lead to the
      disappearance of the heart and major morphologic malformations. Outcome is
      generally unfavourable in 50% of the pregnancies with an acardiac twin.
      Complications in the healthy twin include heart failure, then hydramnios, and
      finally premature delivery which is the cause of most of the deaths. Proposed
      treatment currently relies on treating the heart failure in the healthy twin or
      interrupting vascularization between the two twins leading to in utero death of
      the acardiac twin. Antenatal diagnosis is made by echography and is useful for
      evaluating the prognosis for the pregnancy according to the growth of the
      acardiac twin.

PMID- 8157899
TI  - [Angiotensin-converting enzyme inhibitors and pregnancy. Apropos of 2 cases].
AB  - Angiotensin converting enzyme inhibitors do not have any teratogenic effect in
      man but their use during pregnancy has led to cases of hypotension and subsequent
      severe renal failure in the newborn. The authors report two cases, one involving
      a twin pregnancy which illustrate the variability of the foetal involvement. It
      is emphasized that the side effects of angiotensin converting enzyme inhibitors
      are not only reversible but also are not constantly found.

PMID- 8157900
TI  - [Tumor syndrome of omental origin in the post-partum period].
AB  - The authors report about one case of a tumoral syndrome discovered immediately
      after delivery, the etiology of which proved to be an infarction of omentum
      tumoral-like. On the basis, they study the pregnancy influence on etiology of
      this very rare pathology.

PMID- 8157901
TI  - [Spontaneous cervical extradural hematoma in a pregnant woman].
AB  - Spontaneous spinal extradural hematomas are rare entities, especially during
      pregnancy. The authors report a case of a 26 years old women who developed as
      Brown-Sequard syndrome during pregnancy. The patient underwent first a caesarean
      and thereafter a prompt spinal surgical decompression. Complete sensory-motor
      recovery occurred after 48 hours. Differential diagnosis of cord compression,
      etiology of bleeding, conditions of recovery after surgery are discussed.

PMID- 8157902
TI  - Early out-of-hospital lidocaine administration decreases the incidence of primary
      ventricular fibrillation in acute myocardial infarction.
AB  - This study was designed to assess the effectiveness of early prehospital
      intravenous administration of lidocaine in preventing primary ventricular
      fibrillation (PVF) in patients with suspected acute myocardial infarction (AMI).
      Sixty patients with suspected AMI, seen by the Mobile Coronary Care Unit (MCCU)
      of Florence, were randomly allocated at home to treatment with lidocaine (bolus
      i.v. of 1 mg/kg, followed by an infusion of 4 mg/min) or placebo (infusion of
      saline at a rate of 1 mL/min), respectively. The lidocaine group (27 patients)
      and the control group (33 patients) were not significantly different in age,
      clinical condition, or time of randomization. The diagnosis of AMI was confirmed
      in all 60 patients during the hospital stay. Ventricular fibrillation (VF)
      occurred in 5 patients in the control group in comparison to none in the
      lidocaine group (P < 0.05). Three patients experienced VF at home and were
      successfully resuscitated by an MCCU cardiologist. In another two patients, VF
      occurred during the first 4 hours after onset of symptoms. No major side effects
      were observed after the infusion of lidocaine. Our findings support the
      effectiveness of the prophylactic administration of lidocaine in preventing PVF
      in the prehospital phase of AMI and suggest that the drug can be safely
      administered in this setting by prehospital personnel.

PMID- 8157903
TI  - Accuracy of microcentrifuged hematocrits in the emergency department.
AB  - This study tests whether hematocrits (Hcts) can be accurately measured in an
      emergency department by microcentrifuge technique. Prior to obtaining the results
      of a laboratory Hct (LAB Hct), microcentrifuged Hcts (MC Hcts) were determined on
      204 emergency department patients. The average difference for LAB Hct--MC Hct was
      -0.539 +/- 1.64 (SD). The 95% confidence interval was (-0.76, -0.31) for the
      difference scores and (1.49, 1.81) for the SD. The two techniques had excellent
      correlation (r = 0.96). Plotting the MC Hct against the LAB Hct produced a line
      of best fit that essentially passed through the origin (Y intercept = 0.31) and
      had a slope of 1.006 (both t's < 1). When only the Hct is desired, MC Hcts can be
      performed in place of LAB Hcts without compromising accuracy.

PMID- 8157904
TI  - Tetanus prophylaxis following ocular injuries.
AB  - The administration of prophylaxis against tetanus following a corneal abrasion is
      routinely performed in many acute care facilities, despite a lack of support in
      the literature for its necessity. The risk of developing clinical tetanus from
      three different types of injuries to the eye was evaluated in an animal model.
      Clinical tetanus was induced in unimmunized mice by injecting Clostridium tetani
      organisms or toxin into the anterior chamber. Immunized mice injected
      intracamerally did not develop signs of tetanus. Tetanus was not induced by
      topical inoculation of either live organisms or toxin following corneal
      epithelial debridement or stromal scarification of unimmunized and immunized
      mice. The results of this study support the administration of prophylaxis against
      tetanus following perforating ocular injuries. However, our results do not
      support its routine use following uncomplicated corneal abrasions or other types
      of nonperforating ocular injuries.

PMID- 8157905
TI  - Influence of tidal volume, respiratory rate, and supplemental oxygen flow on
      delivered oxygen fraction using a mouth to mask ventilation device.
AB  - We examined the influence of the following parameters in determining the FiO2
      delivered to a pediatric lung model using the mouth-to-mask method of
      resuscitation: rate of ventilation, inspiratory tidal volumes, and supplemental
      oxygen flow. With a ventilator rate of 20/min and tidal volumes (Vt) < or = 100
      mL, an FiO2 of approximately .50 was observed with a supplemental oxygen flow of
      5 L/min. Increasing the supplemental oxygen flow to 15 L/m did not appreciably
      increase the FiO2 (FiO2 = .53 versus FiO2 = .60, respectively), but did cause a
      significant and unintended increase in Vt. Similar results were noted with a
      ventilator rate of 12/min and Vt < or = 100 mL (FiO2 = .68 versus FiO2 = .73,
      respectively). We also observed a potentially hazardous situation involving the
      positioning of the supplemental oxygen port that might result in high inspiratory
      pressures (stacking of breaths) to the pediatric patient. We believe additional
      testing is warranted prior to widespread use of this device in children.

PMID- 8157906
TI  - Acute renal vascular occlusion: an uncommon mimic.
AB  - Two adult patients with acute renal vascular occlusion with infarction are
      described. Both patients were believed to have ureteral colic. In each instance,
      the correct diagnosis was overlooked at the initial emergency department visit.
      An uncommon clinical entity that continues to go undiagnosed, acute vascular
      occlusion of the kidney must be considered in the differential diagnosis of acute
      flank pain. Absence of the nephrogram phase on an intravenous pyelogram (IVP)
      should alert emergency physicians to this possible diagnosis and to the need for
      further work-up. Subsequent diagnostic evaluation should begin with renal
      ultrasonography to rule out obstructive uropathy. If hydroureteronephrosis is not
      present, follow-up perfusion studies are necessary to confirm the absence of
      renal perfusion. Greater awareness of this uncommon clinical entity and its
      potential morbidity is essential to correct diagnosis and management.

PMID- 8157907
TI  - Scapholunate dissociation: a practical approach for the emergency physician.
AB  - Scapholunate dissociation is an injury caused by forced hyperextension of the
      wrist and results in characteristic radiographic features that may not be
      apparent on routine x-ray studies. In addition, significant ligamentous damage
      may be present even with normal radiographs. If misdiagnosed and improperly
      treated, this injury can lead to chronic wrist pain, instability, and
      degenerative changes. We present an illustrative case, review the pertinent
      literature, and present an algorithm for the evaluation and management of
      scapholunate dissociation.

PMID- 8157908
TI  - Hypokalemia, hypophosphatemia, and compartment syndrome of the leg after downhill
      skiing on moguls.
AB  - Any process that increases intracompartmental pressure may precipitate
      compartment syndrome. We report the case of a patient with hypokalemia and
      hypophosphatemia who presented with compartment syndrome of the legs after a day
      of downhill skiing on moguls. The presentation is followed by a review of the
      pathophysiology, etiology, clinical presentation, and management of compartment
      syndrome, as well as the relationship between hypokalemia, hypophosphatemia, and
      the development of muscle injury.

PMID- 8157909
TI  - Imported cholera in a 31-year-old Peruvian female.
AB  - We present the case of a 31-year-old Peruvian female with severe dehydration due
      to diarrhea and vomiting. The patient was one of a number of travelers arriving
      in Los Angeles on an international flight from Argentina and Peru. Because of the
      travel history and clinical presentation, cholera was suspected and ultimately
      confirmed by stool culture. The patient's clinical course is outlined, and
      discussion of the relevant epidemiology and clinical management of cholera is
      provided. Physicians should suspect cholera when treating patients with severe
      gastroenteritis. The short incubation period, rapid onset of dehydration and
      shock, and high case fatality rate of untreated cholera require a consideration
      of cholera in patients with diarrhea and recent travel to areas where cholera is
      prevalent.

PMID- 8157910
TI  - Recurrent asystole associated with vasovagal reaction during venipuncture.
AB  - A patient with a documented history of 2 asystolic episodes associated with
      venipuncture demonstrates the profound cardioinhibitory effects that vasovagal
      reactions to blood and injury ("blood-injury phobia") can produce. In approaching
      a patient with blood-injury phobia, the clinician should place the patient in the
      Trendelenburg position, apply a cardiac monitor, administer oxygen, and consider
      the need for atropine, transcutaneous pacing, and cough cardiopulmonary
      resuscitation (CPR) prior to venipuncture. Diagnosis of vasovagal syncope is
      discussed. Long-term prophylactic interventions may be beneficial for certain
      patients.

PMID- 8157911
TI  - Malaria: review of features pertinent to the emergency physician.
AB  - Malaria is a health problem of growing concern to the emergency physician.
      Plasmodium vivax, P ovale, and P malaria infections are relatively benign and can
      be treated in an outpatient setting with oral chloroquine or amodiaquine. In
      contrast, P falciparum can present fulminantly, often resulting in death with
      multiple organ system failure. Although quinine historically has been the
      mainstay of therapy for severe falciparum malaria in the United States, and still
      is outside the U.S., quinidine gluconate as a continuous infusion is currently
      recommended as the agent of choice for severe P falciparum infection. In addition
      to the rapid administration of appropriate chemotherapeutic agents and the
      institution of aggressive supportive care, exchange transfusion may be utilized
      as a means of rapidly reducing the parasitemia and consequently, the mortality.

PMID- 8157912
TI  - The management and prevention of tetanus.
AB  - Tetanus is a rare disease in the United States, but it has a high mortality rate
      and is preventable through immunization. Using a computerized literature search,
      we reviewed English language articles on tetanus in the United States. We found
      that despite the availability of an effective vaccine, tetanus still causes
      considerable morbidity. The elderly are at great risk of tetanus, because they
      have never been immunized or their immunity has waned. Emergency physicians can
      reduce the likelihood of tetanus by ensuring appropriate wound care, including
      tetanus immunization and use of tetanus immune globulin, as appropriate.
      Treatment consists of neutralization of circulating toxin, surgical excision to
      eliminate the source of toxin, control of muscle spasms, and prevention of
      respiratory and metabolic complications. A case-finding approach for all persons
      who receive care in emergency departments will reduce the size of the susceptible
      population.

PMID- 8157913
TI  - Wilhelm Konrad Roentgen: a new kind of rays.
AB  - Wilhelm Konrad Roentgen presented a preliminary report on his discovery of x-rays
      in 1895. In his initial experiments with these rays, he had taken a radiograph of
      his wife's hand. This picture immediately implied a medical use for the new
      discovery by demonstrating the bones of the hand. Various aspects of medical
      treatment were soon revolutionized by the technique of radiography. There were
      concerns expressed by the medical community regarding the use of x-rays. Many of
      these concerns regarded deficiencies that were subsequently overcome by technical
      improvements, resulting in a higher quality of radiographs. However, the benefit
      of ever-improving radiographic techniques is undergoing greater scrutiny
      regarding its cost and utility.

PMID- 8157914
TI  - The epidemic of penetrating trauma: a national dilemma.
AB  - Available literature on penetrating trauma in the USA was reviewed to determine
      the prevalence, etiological factors, and societal cost of penetrating trauma.
      Penetrating injuries accounted for 39,888 deaths in 1989 and was the eighth
      leading cause of death. Etiological factors include increasing ownership of
      firearms, alcohol consumption, recreational drug use and trafficking,
      occupational risks, and socioeconomic factors. These injuries account for the
      fourth leading cause of estimated years of potential life lost. Corrective
      strategies and research are severely limited by the disproportionately low
      research funding.

PMID- 8157915
TI  - Prehospital prophylactic lidocaine for uncomplicated acute myocardial infarction.

PMID- 8157916
TI  - Judgement versus professional responsibility.

PMID- 8157917
TI  - Tetanus prophylaxis: protocols require further change and simplification.

PMID- 8157918
TI  - Just how serious is acute lithium overdose and how should it be managed?

PMID- 8157919
TI  - Overdose with sustained-release lithium preparations.

PMID- 8157920
TI  - The problem of atlanto-occipital dislocation.

PMID- 8157921
TI  - Adonis meets Addison: another potential cause of occult adrenal insufficiency.

PMID- 8157922
TI  - Suicidality and HIV status in the emergency department.

PMID- 8157923
TI  - Objectives to direct the training of emergency medicine residents on off-service
      rotations: Internal Medicine. I.
AB  - Internal Medicine is an essential but diverse field. This is the first in a three
      part set of objectives for an off-service rotation in general internal medicine.
      This series may be used to guide the resident during the rotation or to serve as
      part of a teaching program integrated with didactic training and emergency
      department experience.

PMID- 8157924
TI  - My last lecture.

PMID- 8157925
TI  - "Emergency rapport".
AB  - Emergency department encounters between physicians and patients are fraught with
      obstacles to communication. Rapport must be established rapidly in order to
      assure information exchange, patient compliance, and desired treatment outcomes.
      The direct impact of rapport on the quality of medical treatment is reviewed, and
      three common misconceptions regarding physician-patient interaction are
      challenged. Psychologists Bandler and Grinder have provided a model of rapport
      well suited to emergency medicine; their concepts of pacing, anchoring, and
      reframing are presented.

PMID- 8157926
TI  - Deliveries.

PMID- 8157927
TI  - Practicing under the influence.

PMID- 8157928
TI  - Localization of an ecto-ATPase/cell-CAM 105 (C-CAM) in the rat parotid and
      submandibular glands.
AB  - We investigated an ecto-ATPase/cell-CAM 105 (C-CAM), previously shown to be
      distinct from the Ca2+ pump, in rat parotid and submandibular glands. Polyclonal
      antibodies raised against the enzyme were employed using indirect
      immunofluorescence, peroxidase-anti-peroxidase (PAP), and electron microscopic
      immunogold labeling procedures to visualize the location of the enzyme. In the
      PAP-stained sections and with immunofluorescence, labeling was observed on the
      luminal and lateral surfaces and the intercellular canaliculi of the acinar cells
      of both glands. The luminal surface of the intercalated ducts was brightly
      stained, whereas those of the striated and excretory ducts were less prominently
      labeled. The basal surface of the acinar cells in the parotid gland and the
      lateral and basal surfaces of the duct cells were not labeled. Apparent labeling
      was observed on the basal surface of the submandibular acinar cells. Electron
      microscopy revealed that for both glands the enzyme was primarily localized along
      the luminal border of the acinar cells, mainly in association with microvilli,
      with slightly less reactivity along the intercellular canaliculi and lateral
      borders and relatively little along the basolateral membranes. Gold labeling was
      also observed on the luminal borders of the intercalated and striated ducts.
      Possible functions of the C-CAM include breakdown of ATP, stabilization of the
      microvillar membranes, cell adhesion, and involvement in secretory mechanisms.

PMID- 8157929
TI  - Application of electron microscopic immunocytochemistry to the human kidney:
      distribution of type IV and type VI collagen in normal human kidney.
AB  - We used immunogold electron microscopic (IEM) techniques with periodate-lysine
      paraformaldehyde-fixed and Lowicryl-embedded or cryopreserved tissues to study
      the distribution of alpha 1(IV) and alpha 3(IV) chains of Types IV and VI
      collagen in glomerular basement membrane (GBM) and mesangial matrix of glomeruli
      in normal human kidneys. Monoclonal antibodies to alpha 1(IV) and alpha 3(IV)
      collagen chains and Type VI collagen could be detected only with
      cryoultramicrotomy, whereas polyclonal anti-Type IV collagen antibody was
      detectable in Lowicryl-embedded tissue. Ultrastructural detail was better
      preserved in the Lowicryl-embedded tissue. IEM labeling provided more detailed
      information as to the site-specific array of these extracellular matrix molecules
      in glomeruli than did immunofluorescent microscopy. The labeling of alpha 1(IV)
      collagen chain was distributed mainly along the endothelial side of glomerular
      basement membrane and the mesangial matrix. Mesangial GBM was relatively poorly
      labeled compared with that of mesangial matrix. In contrast, the alpha 3(IV)
      chain was detected throughout the thickness of the GBM, but there was no labeling
      of mesangial matrix. Type VI collagen distribution was identical to that of the
      alpha 1(IV) chain within the glomerulus but was also associated with interstitial
      collagen fibrils. This study documents and details the heterogeneous distribution
      of Type IV and VI collagen chains within the normal human glomerulus and provides
      the framework for the study of these matrix components in human glomerular
      diseases.

PMID- 8157930
TI  - Zonal heterogeneity of calcium distribution in rat hepatocytes: an electron
      microscopic study with a combined glutaraldehyde-osmium-pyroantimonate technique.
AB  - Potassium pyroantimonate in combination with osmium tetroxide is an excellent
      technique for investigation of the subcellular distribution of calcium ions in
      glutaraldehyde-fixed liver tissue. Under appropriate incubation conditions
      potassium ions are replaced by calcium ions to form an insoluble electron-dense
      calcium antimonate precipitate. The presence of calcium within this antimonate
      precipitate is confirmed by the electron spectroscopic imaging (ESI) technique.
      Chelator treatment with EGTA [ethylene glycol-bis-(beta-amino-ethyl ether)
      N',N',N'-tetraacetic acid] is usually used as a control, preventing the
      precipitation of calcium. In our investigation, computerized image analysis
      revealed a gradient of the calcium distribution from the periportal to the
      pericentral area. A finely dispersed precipitate was found in the mitochondrial
      matrix and in the euchromatin of the nuclei of the periportal hepatocytes, and in
      the organelles of the pericentral area a coarser deposit in lower concentration
      was recognized. Our findings indicate that periportal and pericentral hepatocytes
      retain their zonal characteristics also with respect to calcium concentration in
      mitochondria and nuclei.

PMID- 8157931
TI  - Microcytophotometric analysis of human osteoclast metabolism: lack of activity in
      certain oxidative pathways indicates inability to sustain biosynthesis during
      resorption.
AB  - It has been proposed that highly biosynthetic cells oxidize fatty acids to
      generate ATP while maintaining high levels of glucose metabolism through the
      glycolytic and pentose shunt systems to supply biosynthetic intermediates. We
      investigated the metabolic strategies and substrate for ATP production in the
      osteoclast. We used in situ quantitative microcytophotometric techniques to
      determine the maximal activity of the pentose shunt (glucose-6-phosphate
      dehydrogenase; G6PD), the glycolytic pathway (glyceraldehyde-3-phosphate
      dehydrogenase and lactate dehydrogenase; G3PD and LDH), fatty acid oxidation
      (beta-hydroxyacyl dehydrogenase; HOAD), and the Krebs cycle (succinate
      dehydrogenase; SDH) in human osteoclasts in situ, and related these enzyme
      activities to the degree of involvement of the cells in resorption. Unlike other
      highly biosynthetic cells, such as chondrocytes and macrophage polykaryons,
      osteoclasts associated with bone resorption were deficient in G3PD, LDH, and G6PD
      activity. However, osteoclasts did demonstrate a capacity for fatty acid
      oxidation which increased in cells apposed to the bone surface. The lack of
      significant glycolytic and pentose shunt activity in the osteoclast provides good
      evidence that resorbing osteoclasts, unlike phagocytosing macrophage polykaryons,
      have the metabolic characteristics of cells with greatly reduced capabilities of
      de novo mRNA synthesis but which do maintain high rates of ATP production. The
      possibility that the loss of glycolytic activity is a prelude to cell death is
      discussed.

PMID- 8157932
TI  - Immunohistochemical detection of ornithine decarboxylase in individual cells:
      potential application for in vitro chemosensitivity assays.
AB  - Ornithine decarboxylase (ODC), which catalyzes the rate-limiting step in the
      biosynthesis of polyamines, can serve as a marker of proliferation. The presence
      of ODC protein in individual cells was quantitatively detected by an
      immunofluorescence assay using an ACAS 570 computerized fluorescence microscope.
      ODC was detected in KB-3-1 human epithelial carcinoma cells grown in the absence
      of any drug. Vinblastine, which inhibits cell growth, caused the disappearance of
      ODC. On the other hand, ODC was detected in multidrug-resistant cells grown in
      the absence or in the presence of vinblastine. NIH 3T3 fibroblasts transformed by
      the c-Ha-ras oncogene also contained ODC protein. This protein disappeared when
      the cells were treated with cycloheximide, which inhibits cell proliferation.
      These findings suggest that ODC can be detected in individual cells by
      immunofluorescence. Whether this method can be used for in vitro chemosensitivity
      tests remains to be studied.

PMID- 8157933
TI  - In situ nick-translation detects focal apoptosis in thymuses of glucocorticoid-
      and lipopolysaccharide-treated mice.
AB  - In this study we used in situ nick-translation to analyze apoptotic events in the
      thymus and in cultured thymocytes at the level of individual cell nuclei. In
      vitro nuclear DNA strand breaks were observed 3 hr after exposure of thymocytes
      to dexamethasone (Dex) in 30% of cells and increased to 78% after 15 hr. In
      sections of 10-day-old mouse thymus, single cells with DNA strand breaks were
      dispersed throughout the cortex and to a lesser degree in the medulla. In
      contrast, a large number of clusters of apoptotic cells were seen in the thymic
      cortex 3-18 hr after injection of Dex or lipopolysaccharide (LPS). After 48 hr
      apoptotic cells were no longer detectable. Positive signals correlated with the
      detection of DNA ladders of multimers of about 180 BP size on agarose gels.
      Electron microscopy confirmed the presence of apoptotic cell clusters and showed
      that apoptotic foci were located around capillaries in LPS-injected animals. We
      conclude that in situ nick translation is a suitable method to detect apoptotic
      nuclei in cultured cells and on cryostat sections. With this method we could
      demonstrate that in vivo spontaneous apoptosis occurs in single dispersed
      thymocytes, also including the medulla, whereas experimentally induced apoptosis
      affects cell clusters, possibly due to high local concentrations of apoptosis
      inducers.

PMID- 8157934
TI  - Use of quantitative image microfluorometry to follow fluorescent ricin
      internalization in single living cells.
AB  - We used microspectrofluorometry and videomicrofluorometry to follow the binding
      and internalization of fluorescein-labeled toxic lectin ricin in living Zajdela
      hepatoma cells. Microspectrofluorometry showed that when ricin was specifically
      labeled on its B-chain with one molecule of fluorescein (ABF), its fluorescence
      spectrum did not alter during its binding to the cell surface and subsequent
      internalization. This enabled us to use image analysis to follow cell
      internalization of labeled ricin. Accordingly, we measured the appropriate
      fluorescent cell parameters, comprising total fluorescence intensity, cell
      surface area, mean fluorescence intensity and its standard error, and used the
      measurements for mono- and biparametric studies of cell fluorescence
      distribution. The results showed that (a) ricin binds two different
      subpopulations of Zajdela hepatoma cells, (b) Zajdela hepatoma cells internalize
      ricin rapidly and after a relatively stable period of 1-2 hr, internalization
      starts again at 4 hr, and (c) the distribution of intracellular fluorescence is
      heterogeneous and ABF accumulates in certain cellular localizations. Our results
      demonstrate that quantitative microfluorometry is an effective and interesting
      approach for real-time studies of macromolecule internalization in living cells.

PMID- 8157935
TI  - Morphometric studies of the localization of the glucocorticoid receptor in
      mammalian cells and of glucocorticoid hormone-induced effects.
AB  - We studied the subcellular distribution of the glucocorticoid receptor (GR) by
      light microscopy (LM) and confocal laser scanning microscopy (CLSM) in different
      mammalian cell types. The effect of added glucocorticoid hormones on GR
      distribution was investigated by photometric quantitation on optical sections
      obtained by CLSM followed by statistical analysis. In the control interphase
      cytoplasm, the distribution of GR was fibrillar in some and diffuse in other cell
      types. Fibrillar GR was distributed along cytoplasmic microtubules (MTs) with
      predilection for a subset of MTs. GR was also observed in the centrosomes.
      Nuclear GR was both diffuse and granular in distribution. During cell division,
      GR appeared in the mitotic apparatus at all stages of mitosis. These findings
      were not fixation-dependent. Glucocorticoid treatment increased both the nuclear
      and cytoplasmic GR signal. However, this was detectable only after precipitating
      but not cross-linking fixation. There was both intra- and intercellular GR
      heterogeneity in the absence and presence of hormone but no indication of a
      hormone-induced nuclear translocation of GR. We present a hypothetical model of
      two independent GR populations in the nucleus and cytoplasm, respectively,
      without any discernible ligand-induced nuclear translocation of GR. The
      extranuclear GR population may exert effect(s) on site in the cytoplasm without
      involving nuclear genomic transcription.

PMID- 8157936
TI  - Immunocytochemical localization of human 5 alpha-reductase 2 with polyclonal
      antibodies in androgen target and non-target human tissues.
AB  - We studied the tissue distribution and cellular localization of 5 alpha-reductase
      2, the human prostatic isoenzyme, in different human tissues, both cryostat
      sectioned and paraffin-embedded. Polyclonal antibodies raised in rabbits against
      a native peptide (C-terminal amino acids 229-254) or synthetic peptides (amino
      acids 234-245), either as carrier-conjugated linear peptides or multiple antigen
      peptides (MAP), were assayed for specificity and sensitivity with Western
      blotting and an ELISA system. One antibody showing monospecificity on Western
      blots and in ELISA was used for immunohistochemical detection of the respective
      antigen in tissues from male and female subjects. Positive cells were found (with
      decreasing intensity) in inner epithelial sheath of hair follicles, pyramidal
      cells of the cerebral cortex, hepatocytes and bile duct cells, prostate
      epithelial cells, seminal vesicle epithelial cells, endothelial cells of small
      vessels, fat cells, fibrocytes of genital and extragenital organs, and smooth
      muscle cells of prostate and seminal vesicles. Some variation in the
      immunoreactivity of testis and ovary tissue was seen with different antibodies. 5
      alpha-Reductase 2 is obviously not restricted to androgen target organs in the
      male, but is present in a large number of cells and tissues in both males and
      females.

PMID- 8157937
TI  - Demonstration of desmosomal antigens by electron microscopy using cryofixed and
      cryosubstituted skin with silver-enhanced gold probe.
AB  - In a previous post-embedding immunogold electron microscopic (EM) studies,
      localization of various desmosomal antigens was possible at high but not at low
      magnification. We developed a method for simultaneous demonstration of epidermal
      desmosomal antigens at both low- and high-power EM magnifications by a method
      based on cryofixation and acetone cryosubstitution and the use of a 1-nm gold
      probe with silver enhancement. Ultra-thin sections of Lowicryl K11M were
      incubated with primary antibodies against desmoplakin, desmocollin, or
      desmoglein, followed by 1-nm gold-conjugated secondary antibody. Silver
      enhancement for 12 min provided the ideal labeling size for low-power
      visualization, whereas silver enhancement for 4-6 min was ideal for high-power EM
      observation. Each desmosome immunolabeled with the gold probe was clearly
      demonstrated, even at very low-power magnification. The level of background
      labeling could be determined easily and the area of interest for high-power
      observation selected accurately. The fine ultrastructural appearance of
      desmosomal molecules was precisely demonstrated on high-power observation. This
      system should be useful for the immunocytochemical study of a variety of
      desmosomal antigens as well as other molecules of interest.

PMID- 8157939
TI  - Bibliography of the current world literature in hypertension.

PMID- 8157938
TI  - The study of intralobular heterogeneity of enzyme activity in livers with the use
      of invalid histochemical methods.

PMID- 8157940
TI  - Prostaglandins and their receptors: II. Receptor structure and signal
      transduction.

PMID- 8157941
TI  - Intracellular Ca2+ and force generation determined in resistance arteries of
      normotensive and hypertensive rats.
AB  - OBJECTIVE: Dysfunctional cellular Ca2+ handling has been proposed to underlie the
      heightened vascular reactivity observed in the spontaneously hypertensive rat
      (SHR) model of genetic hypertension. We tested the hypothesis that basal or
      agonist-induced mobilization of intracellular Ca2+ is elevated in mesenteric
      resistance arteries of SHR compared with the normotensive Wistar-Kyoto (WKY) rat.
      DESIGN: A method using fura-2 for the simultaneous measurement of intracellular
      Ca2+ and isometric force generation in isolated mesenteric resistance arteries
      was employed to measure agonist-induced changes in Ca2+ and force during
      activation with 100 mmol/l K+ or 10 mumol/l norepinephrine. Arteries with
      normalized diameter 220-240 microns from male rats aged 14-15 weeks were
      examined. RESULTS: No differences were detected between the rat strains in basal
      Ca2+ concentration or the steady-state concentration of Ca2+ achieved in response
      to either 100 mmol/l K+ or 10 mumol/l norepinephrine. The relationship between
      Ca2+ and force during the contractile responses to K+ and norepinephrine was
      analyzed. No differences between the strains in the level of active stress,
      normalized to unit intracellular Ca2+, were detected in the steady-state
      responses to K+ or norepinephrine. CONCLUSIONS: The present results do not
      support the hypothesis that alterations in either the basal concentration of
      intracellular Ca2+ or the amount of intracellular Ca2+ mobilized in response to
      high levels of norepinephrine or K+ are present in resistance arteries of SHR
      compared with those of WKY rats. Moreover, these findings suggest that elevations
      in Ca2+ do not contribute to heightened peripheral resistance in SHR.

PMID- 8157942
TI  - Direct and indirect effects of carbenoxolone on responses to glucocorticoids and
      noradrenaline in rat aorta.
AB  - BACKGROUND: In the kidney carbenoxolone impairs inactivation of glucocorticoids
      and facilitates their access to mineralocorticoid receptors by inhibiting 11 beta
      hydroxysteroid dehydrogenase (11 beta-OHSD). 11 beta-OHSD is also expressed in
      vascular smooth muscle, and, in humans, carbenoxolone potentiates vasoconstrictor
      sensitivity to cortisol and noradrenaline. OBJECTIVE: To establish in vitro
      whether the vascular effects of carbenoxolone are mediated by inhibition of 11
      beta-OHSD. METHODS: Noradrenaline-induced vasoconstriction was measured in
      helical de-endothelialized rat aortic strips following 2-5 h exposure to one or
      more of: carbenoxolone, corticosterone, a mineralocorticoid-receptor antagonist
      (spironolactone) and a glucocorticoid- and progesterone-receptor antagonist (RU
      38486). RESULTS: Carbenoxolone potentiated noradrenaline-induced vasoconstriction
      in aortae from adrenalectomized rats, an effect which was prevented by
      spironolactone but not by RU 38486. By contrast, when corticosterone was added or
      when aortae from non-adrenalectomized rats were studied, carbenoxolone attenuated
      noradrenaline-induced vasoconstriction. CONCLUSIONS: Carbenoxolone has a direct
      effect, independent of 11 beta-OHSD, which potentiates noradrenaline-induced
      vasoconstriction and might be mediated by activation of mineralocorticoid
      receptors. Carbenoxolone also has an indirect effect, attenuating noradrenaline
      induced vasoconstriction dependent on corticosterone and, therefore, mediated by
      inhibition of 11 beta-OHSD. Although experiments with carbenoxolone must be
      interpreted with caution because of its direct effect, the present data confirm
      that 11 beta-OHSD modulates vascular sensitivity to glucocorticoids and
      noradrenaline. Therefore, 11 beta-OHSD activity might influence blood pressure by
      effects in both the kidney and the vasculature.

PMID- 8157943
TI  - Selective impairment of endothelium-dependent relaxations by prostaglandin
      endoperoxide.
AB  - OBJECTIVE: Studies of aortas from hypertensive and diabetic rats and rabbits have
      demonstrated impairment of endothelium-dependent relaxations, which were
      associated with increased release of endothelium-derived thromboxane A2 (TXA2).
      This implicates enhanced release of TXA2 or its precursor prostanoid,
      prostaglandin endoperoxide (PGH2), or both, as factors mediating the endothelial
      cell dysfunction. METHODS: The interaction of vasoconstrictor prostanoids (PGH2,
      PGF2 alpha and U-46619, a stable thromboxane-receptor agonist) and oxygen-derived
      free radicals with the release of nitric oxide was examined in isolated aortas
      from Sprague-Dawley rats. RESULTS: Exogenously applied PGH2 or U-46619 caused
      concentration-dependent contractions of aortic rings, these contractions being
      blocked by the newly developed, potent and selective PGH2- and TXA2-receptor
      antagonist BMS-180291, but not by inhibition of TXA synthase or cyclo-oxygenase
      (using dazoxiben and indomethacin, respectively). In aortic rings contracted
      submaximally with phenylephrine, brief exposure to a subthreshold concentration
      of PGH2 caused impairment of acetylcholine- and ADP-induced, but not of
      nitroprusside-induced, relaxations. The impairment was restored towards normal by
      BMS-180291 or by superoxide dismutase (SOD), a superoxide anion scavenger, but
      not by dazoxiben or indomethacin. In contrast, treatment of aortic rings with U
      46619 or PGF2 alpha did not impair the relaxations. Oxygen-derived free radicals
      generated by xanthine oxidase caused contractions and impaired acetylcholine
      relaxations which were reversed by SOD but not by BMS-180291. CONCLUSIONS: These
      findings indicate that activation of PGH2 receptors causes contractions and
      selective impairment of endothelium-dependent relaxations by a mechanism
      involving generation of oxygen-derived free radicals in the endothelium.

PMID- 8157944
TI  - Sensitivity to ischaemic ATP breakdown in different models of cardiac hypertrophy
      in rats.
AB  - OBJECTIVE: To evaluate the sensitivity to ischaemia of rat hearts made
      hypertrophic by pressure overload [two-kidney, one clip (2-K,1C) rats], volume
      overload (aortocaval arteriovenous shunt), minoxidil or isoproterenol. METHODS:
      Ischaemia was induced in the isolated perfused hearts by a stepwise lowering of
      the perfusion pressure; at each step the coronary effluent was assessed for the
      products of ATP breakdown. RESULTS: Hypertension increased cardiac weight by 35
      and 56% after 2.5 and 12 weeks, respectively. Volume overload increased heart
      weight by 25 and 55% after 1 and 12 weeks, respectively. Minoxidil (for 5 weeks)
      or isoproterenol (for 1 week) increased cardiac weight by 22 and 16%,
      respectively. The hearts from 2-K,1C rats started to release ATP catabolites in
      the coronary effluent at a substantially higher perfusion pressure, and with
      significantly higher maximal levels, than the control hearts. In contrast, in
      volume overload cardiac ATP breakdown was similar to that in the controls, and
      isoproterenol administration caused significantly lower levels of ATP breakdown.
      At identical flow rates, normalized per gram dry tissue, the purine concentration
      in the coronary effluent was similar in all of the models of cardiac hypertrophy
      studied and in the respective controls, and was even lower in the long-term
      volume-overloaded and isoproterenol-induced hypertrophic hearts. CONCLUSIONS: We
      conclude that hearts from hypertensive rats are more sensitive to ischaemic ATP
      breakdown during lowering of perfusion pressure than hearts from volume
      overloaded or control rats. This is independent of the duration of the
      hypertrophic process, and can be explained by a lower coronary flow per gram
      heart tissue at a given perfusion pressure. This conclusion is strengthened by
      the observation that hypertrophic hearts from volume-overloaded rats had similar
      amounts of cardiac hypertrophy to the hearts from the hypertensive rats, without
      a change in flow, coronary vascular resistance or ischaemic sensitivity, whereas
      the hearts from isoproterenol-treated rats had lower ischaemic sensitivity and
      coronary vascular resistance.

PMID- 8157945
TI  - Influence of cholesterol lowering on plasma membrane lipids and cationic
      transport systems.
AB  - BACKGROUND: In order to determine whether alterations in membrane lipids affect
      transmembrane cationic transport systems in erythrocytes and platelets, cationic
      fluxes and intracellular cationic concentrations were measured in
      hypercholesterolaemic patients before and during administration of an inhibitor
      of 3-hydroxy-3-methlglutaryl coenzyme A reductase. METHODS: After a 1-month run
      in placebo period on a lipid-lowering diet the patients were treated, in a double
      blind manner, with either placebo (n = 25) or pravastatin (n = 25) for 6 months.
      Placebo or pravastatin (10 mg during the first month, 20 mg during the second
      month and 40 mg during the remaining 4 months) was administered once a day in the
      evening. RESULTS: Compared with the placebo group, the erythrocyte and platelet
      membrane cholesterol content was reduced in the patients treated with
      pravastatin. The intra-erythrocyte and intraplatelet Na+ concentration was
      reduced during pravastatin administration, whereas the activity of the
      erythrocyte and platelet Na(+)-K+ pump was increased. However, the intra
      erythrocyte and intraplatelet K+, Mg2+ and cytosolic Ca2+ concentrations, and
      water content, as well as the activities of the erythrocyte Na(+)-Li+
      countertransporter and Na+,K+ cotransporter, and Na+ and K+ leakage, were not
      changed during pravastatin treatment. CONCLUSIONS: The present data show that
      cholesterol lowering in hypercholesterolaemic patients may result in a
      significant decrease in erythrocyte and platelet membrane cholesterol content.
      These changes in membrane cholesterol are accompanied by an increase in activity
      of the Na(+)-K+ pump and a decrease in intra-erythrocyte and intraplatelet Na+
      concentrations.

PMID- 8157946
TI  - Structural adaptation of the heart in borderline hypertensives in response to
      blood pressure lowering with captopril.
AB  - OBJECTIVE: To determine whether treatment of borderline hypertension reverses the
      cardiac 'amplifier' effect associated with increased left ventricular mass.
      DESIGN: Randomized, double-blind, placebo-controlled trial involving treatment
      for 6 months. SETTING: Ambulant outpatients in a teaching hospital. PARTICIPANTS:
      Recruited by local doctor referral or worksite screening. Average of two readings
      of entry blood pressures taken 1 week apart 140-160 mmHg (systolic) or 90-95 mmHg
      diastolic, or both. Twenty-six previously untreated males, mean +/- SD age 33 +/-
      9.2 years with mean +/- SD blood pressure 138 +/- 7.4/90 +/- 7.0 mmHg entered and
      completed the study. INTERVENTIONS: Twelve subjects received captopril, average
      dose 72 mg/day for 24 weeks, the remainder receiving placebo. MAIN OUTCOME
      MEASURES: Echocardiographic left ventricular dimensions, mass and transmitral
      Doppler flow, as well as office, ambulatory and exercise blood pressure. RESULTS:
      In the captopril group blood pressure was reduced significantly. Left ventricular
      mass decreased significantly from 205 to 195 g at 8 weeks and to 202 g at 24
      weeks, returning to 232 g 4 weeks after treatment. Interventricular septum
      thickness fell significantly at 24 weeks. Doppler parameters did not alter.
      Baseline 8-h ambulatory blood pressure did not change with treatment. The
      reduction in peak exercise systolic blood pressure in the captopril group was not
      different from the change in the placebo group. CONCLUSION: Blood pressure can be
      effectively lowered using captopril in young subjects with borderline
      hypertension. Treatment is well tolerated and leads to regression of left
      ventricular wall thickness and mass, suggesting that treatment of blood pressure
      elevations may be advisable at lower levels than currently recommended.

PMID- 8157947
TI  - Differences in the chronic hypotensive mechanism of action of ketanserin in
      spontaneously hypertensive and Wistar-Kyoto rats.
AB  - OBJECTIVE: To investigate the hypotensive effect and mechanism of action of
      chronic administration of ketanserin in spontaneously hypertensive rats (SHR) and
      in normotensive Wistar-Kyoto (WKY) rats. METHODS AND RESULTS: SHR and WKY rats
      were given chronic ketanserin infusions via osmotic minipumps to minimize
      fluctuations in drug concentrations and receptor responsiveness. In SHR treated
      with intravenous infusions of 3.0 (n = 9) or 6.0 mg/kg per day (n = 8) ketanserin
      for 7 days, significant dose-dependent falls in systolic blood pressure (SBP)
      were observed during the infusion period. Heart rate did not change in either the
      vehicle- or the ketanserin-treated groups of SHR. In WKY rats intravenously
      infused with 3.0 (n = 9) or 6.0 mg/kg per day (n = 10) ketanserin, dose-dependent
      falls in SBP were also observed during the infusion period, with the changes
      reaching statistical significance at the 6.0 mg/kg per day dose. The changes in
      heart rate were not different from those in control rats. Pressor responses to
      the type 2 5-hydroxytryptamine (5HT2)-receptor agonist (+/-)-alpha-methyl-5
      hydroxytryptamine (5.0-125.0 micrograms/kg), as assessed on day 7, were reduced
      dose-dependently in all ketanserin-infused rats. alpha 1-Adrenoceptor responses
      to 1.0-10.0 micrograms/kg intravenous phenylephrine were attenuated in only the
      WKY rats infused with 6.0 mg/kg per day ketanserin. In the SHR treated with
      ketanserin there was no change in the pressor responsiveness to phenylephrine.
      Baroreflex sensitivity on day 7 was significantly greater in the ketanserin
      infused SHR than in their respective controls. Changes in baroreflex sensitivity
      were not significantly different in WKY rats following ketanserin infusion.
      CONCLUSIONS: These results show that chronic administration of ketanserin lowers
      blood pressure in both SHR and WKY rats. In SHR the alpha 1-adrenoceptor-blocking
      effects of ketanserin are compensated for, and the reduction in blood pressure by
      day 7 is maintained predominantly by, 5HT2-receptor blockade. In WKY rats
      ketanserin-induced hypotension is associated with concomitant blockade of 5HT2-
      and alpha 1-receptors. The present study therefore suggests a differential
      mechanism of action of ketanserin in hypertensive and normotensive rats during
      chronic treatment.

PMID- 8157948
TI  - Regression of hypertensive myocardial hypertrophy does not affect ultrasonic
      myocardial reflectivity: a tissue characterization study.
AB  - OBJECTIVE: Ultrasonic backscatter from the myocardial walls is directly related
      to the morphometrically or biochemically evaluated collagen content in man, and
      shows a normal pattern of quantitatively assessed ultrasonic backscatter in
      hypertensive patients, even in the presence of left ventricular hypertrophy.
      Whether the pharmacologically induced regression of left ventricular hypertrophy
      in hypertensive patients is accompanied by a disproportionate increase in
      relative connective tissue content is not yet known. The objective of the present
      study was to assess the effects of regression of left ventricular hypertrophy on
      the quantitatively evaluated myocardial reflectivity in essential hypertensives.
      DESIGN: We evaluated 19 mild-to-moderate essential hypertensives with
      echocardiographically assessed left ventricular hypertrophy, before and after 8
      months' effective antihypertensive therapy with 20-40 mg enalapril once a day,
      associated with diuretics or calcium antagonists, or both, in six patients to
      achieve optimal blood pressure control. Using a modified echo machine developed
      in the Institute of Clinical Physiology, Pisa, an on-line radio-frequency
      analysis was performed to obtain quantitative operator-independent measurements
      of the integrated backscatter signal of the ventricular septum and the posterior
      wall. The integrated values of the radio-frequency signal from the myocardial
      walls were normalized for those from the pericardial interface and were expressed
      as percentages (integrated backscatter index). RESULTS: In comparison with
      baseline, the treated hypertensives showed significant decreases in mean blood
      pressure, left ventricular mass index, and septal and posterior wall thickness.
      However, integrated backscatter index values were similar at baseline and after
      therapy for both the septum and the posterior wall. CONCLUSION: Antihypertensive
      therapy with enalapril does not increase myocardial reflectivity, although it
      does induce regression of left ventricular hypertrophy. This suggests that, in
      accord with experimental data, regression of hypertrophy is achieved by enalapril
      through a proportionate regression of the myocyte and connective tissue
      components of the myocardium.

PMID- 8157949
TI  - Insulin resistance is coupled to low physical fitness in normotensive men with a
      family history of hypertension.
AB  - OBJECTIVE: To investigate insulin sensitivity and the influence of level of
      physical fitness in men with a family history of hypertension and in control
      subjects. DESIGN: Insulin sensitivity was determined and physical fitness
      estimated in 39 normotensive, glucose-tolerant men with a family history of
      hypertension (Relatives group) and in 29 age- and body mass index-matched
      normotensive men with no such family history (Controls group). METHODS: The
      euglycaemic hyperinsulinaemic clamp technique (steady-state insulin concentration
      approximately 100 mU/l) was used to determine insulin sensitivity. Physical
      fitness, measured as maximal oxygen uptake, was estimated from the heart rate
      response to a submaximal exercise test. RESULTS: Insulin sensitivity index and
      estimated maximal oxygen uptake were lower in the Relatives than in the Controls.
      There was a positive correlation between insulin sensitivity and maximal oxygen
      uptake in both groups. In the Controls there was a negative correlation between
      insulin sensitivity and waist:hip ratio, but this relationship was not found in
      the Relatives. CONCLUSIONS: The present findings indicate that reduction of
      insulin sensitivity precedes the development of high blood pressure and may be
      coupled to low physical fitness. As abdominal fat distribution seems not to be
      related to insulin sensitivity in subjects with a family history of hypertension,
      changes in muscle fibre composition or muscle glucose metabolism, or both, might
      explain the lower insulin sensitivity and physical fitness in the Relatives.

PMID- 8157950
TI  - Five-year follow-up of blood pressure and left ventricular mass in children with
      different maternal histories of hypertension: the Hypertension in Pregnancy
      Offspring Study.
AB  - OBJECTIVE: To follow the changes in blood pressure and echocardiographically
      determined left ventricular mass in offspring of mothers who had hypertension
      during pregnancy. DESIGN: Longitudinal study with a 5-year follow-up. METHODS:
      Nineteen offspring of mothers who had hypertension during pregnancy, and
      sustained hypertension at follow-up 7-12 years after term, were examined, by
      blood pressure measurement and M-mode echocardiography, at a mean age of 12.8
      years (range 10.6-16.4) and were re-examined 5.6 years later. For comparison, 17
      children born to mothers who had hypertension during pregnancy, but were
      normotensive at follow-up, were also examined. A control group of children born
      following a normotensive pregnancy was also recruited. Comparisons were made by
      analysis of variance among the three groups. RESULTS: At the initial examination
      systolic blood pressure was significantly higher in the children born to mothers
      who had hypertension during pregnancy and were hypertensive at follow-up. This
      difference persisted in the adolescents at follow-up. No differences among the
      three groups in echocardiographically determined left ventricular mass were seen,
      either at the initial examination or at follow-up. There was a significant
      correlation between left ventricular masses determined 5 years apart (r = 0.53, P
      < 0.001). CONCLUSIONS: The present longitudinal study demonstrates that offspring
      of mothers with hypertension during pregnancy, that was sustained at follow-up,
      have higher blood pressure than controls. Children with different maternal
      histories of hypertension maintain their rank with regard to left ventricular
      mass during adolescence.

PMID- 8157951
TI  - Ethnicity and the relationship of sodium intake to blood pressure.
AB  - OBJECTIVE: To examine the impact of race on the relationship between sodium
      intake and blood pressure. METHODS: We examined the blood pressure levels and 24
      h urinary sodium excretion of 808 (355 Black, 453 Caucasian) union members who
      participated in a workplace hypertension control program. The 808 study subjects,
      who met the criterion for accuracy of urine collection, included 627 untreated
      hypertensives (systolic blood pressure > or = 160 mmHg or diastolic blood
      pressure > or = 95 mmHg, or both) and 181 normotensives (blood pressure < 160/95
      mmHg). RESULTS: In univariate analysis, the age-adjusted mean diastolic blood
      pressure levels of the Black subjects exceeded those of the Caucasian subjects at
      a significance level that was marginal for the male and very high for the female
      subjects. No differences were observed in mean systolic blood pressure between
      the Black and Caucasian subjects. Within each racial grouping, the subjects were
      grouped by sex-specific tertile of urinary sodium excretion in order to compare
      baseline characteristics and blood pressure levels. Small differences between the
      Black and Caucasian males in age-adjusted blood pressure within each urinary
      sodium excretion category were further diminished after adjusting for confounding
      factors. Significant differences between the Black and Caucasian females in age
      adjusted diastolic blood pressure within each urinary sodium excretion group
      became non-significant when further adjusted for weight or body mass index, or
      both. These findings are in agreement with those observed in multiple linear
      regression models. CONCLUSION: In this socio-economically homogeneous group, when
      confounding factors are considered, Black and Caucasian subjects have similar
      blood pressure levels at the same level of 24-h urinary sodium excretion.
      Ethnicity itself was not found to influence the relationship between sodium
      intake and blood pressure.

PMID- 8157952
TI  - Phenotypic and functional cellular differences between human CD3- decidual and
      peripheral blood leukocytes.
AB  - CD3- leukocyte clones derived from human decidualized endometrial tissue of first
      trimester pregnancy have been compared with CD3- PBL clones. Most CD3- decidual
      granulated leukocyte (DGL) clones were CD16- CD56+, whereas most CD3- PBL clones
      were CD16+ CD56+. CD3- DGL and PBL clones, whether CD16+ or not, showed MHC
      nonrestricted NK cell activity. However, CD3- CD16- DGL clones had low cytotoxic
      activity against the NK-resistant cell line BSM, whereas CD3- CD16+ DGL and CD3-
      PBL clones were strongly cytotoxic. Cytolytic activity has also been investigated
      in respect of target cell HLA-G expression, because this nonpolymorphic class I
      MHC molecule is expressed selectively by invasive fetal cytotrophoblast. Class I
      HLA Ag loss cell mutants were killed efficiently by CD3- DGL clones. Expression
      of transfected HLA-B8 increased their sensitivity to lysis by most CD3- DGL
      clones, whereas expression of transfected HLA-G commonly led to decreased target
      cell killing. In addition, the effects of uncloned CD3- DGL on the one-way MLR
      have been examined. These cells were very poor responders and, unless cultured to
      induce expression of class II MHC molecules, were also very poor stimulators.
      When fresh CD3- DGLs were added as third-party cells, either autologous or
      allogeneic to responder cells, [3H]TdR incorporation was decreased in the MLR.
      Thus, CD3- DGL clones express MHC-nonrestricted cytolytic activity, notably
      against HLA-negative cells, but expression of HLA-G offers protection to target
      cells. In addition, CD3- DGL may function to suppress allogeneic responses.

PMID- 8157953
TI  - Control of the rat T cell response to retroviral and bacterial superantigens by
      class II MHC products and Tcrb-V8.2 alleles.
AB  - The in vitro response of unprimed rat T cells to retroviral and bacterial
      superantigens (SAg) was analyzed with TCR V beta 8.2-, 8.5-, 10-, and 16-specific
      mAbs. Specific stimulation of V beta 8.2 and 8.5 CD4 cells was observed in the
      response to Mls1a, the retroviral SAg encoded by integrated provirus Mtv-7 (Mtv-7
      SAg), which was presented by mouse B cells or mouse fibroblasts transfected with
      DR1 genes and the Mtv-7 SAg. Additionally, a strong response of V beta 16 CD4
      cells to an as yet unidentified mouse SAg was found. Only some of the bacterial
      SAg known to stimulate mouse and human T cells also activated rat lymph node
      cells. SEA, SEE, and TSST-1 stimulated rat T cells well; SEB, SEC1, and SED did
      not. This defect was apparently a result of weak binding to rat MHC class II
      molecules because presentation by human MHC class II molecules restored T cell
      activation. Under these conditions, SEB stimulated V beta 8.2+ and 8.5+ CD4 and
      CD8 cells from Lewis rats. A comparison of several rat strains revealed an
      unresponsiveness to SEB or Mtv-7 SAg for V beta 8.2 cells from F344 and DA rats.
      Determination of the nucleotide sequences of the Tcrb-V8.2 of these strains
      revealed differences between SAg-responsive and SAg-unresponsive Tcrb-V8.2 in
      seven amino acids, four of them located in the putative SAg contact site. The
      significance of these findings for the evolution of TCR-SAg interactions is
      discussed.

PMID- 8157955
TI  - In vivo administration of insulin-like growth factor-I stimulates primary B
      lymphopoiesis and enhances lymphocyte recovery after bone marrow transplantation.
AB  - Recombinant human insulin-like growth factor-I (IGF-I) (100 micrograms/day) was
      infused by osmotic minipumps into mice to evaluate its effects on bone marrow B
      lymphopoiesis. IGF-I treatment resulted in a significant increase in the total
      number of bone marrow B lineage cells by 2 wk post-treatment in both normal,
      adult mice and animals that had been lethally irradiated and reconstituted with
      syngeneic bone marrow. Effects were still apparent at wk 3, even though pumps
      delivered IGF-I for only 14 days. In addition, the results confirm previous
      observations that IGF-I treatment results in an increase in numbers of splenic B
      cells and suggest that this is in part the result of stimulation of B cell
      proliferation in that organ.

PMID- 8157954
TI  - Failure to demonstrate long-lived MHC saturation both in vitro and in vivo.
      Implications for therapeutic potential of MHC-blocking peptides.
AB  - Peptides that bind with high affinity to class II MHC molecules can inhibit T
      cell activation both in vitro and in vivo. Thus, they have been suggested as
      potential therapeutic agents for MHC-associated autoimmune diseases. We have
      constructed nonnatural peptides with high affinity for certain disease-associated
      MHC alleles. More specifically, a particular peptide, designated as CY-760.50,
      was found to have a high binding affinity for DR1, slow dissociation kinetics
      after binding to MHC, and prolonged stability in human serum. However, when the
      ability of this peptide to block peptide presentation to an influenza
      hemagglutinin 307-319 peptide-specific, DR1-restricted T cell clone was examined,
      it was found that MHC blockade could only be achieved when high concentrations of
      peptide were present along with Ag in the fluid phase. Thus, pretreatment of APC
      with MHC class II blocker, followed by removal of unbound blocker, did not result
      in saturation of MHC molecules, because practically immediate reacquisition of Ag
      presenting capacity was observed after removal of fluid phase blocker. The
      pharmacokinetic behavior and the duration of blocking activity of CY-760.50 were
      also examined in vivo, taking advantage of the fact that the mouse MHC class II
      molecule I-Ab also bound CY-760.50 with high affinity. CY-760.50 administered
      i.v. to C57BL/6 mice was rapidly cleared from the circulation and virtually
      undetectable in the serum 10 min after injection. This fast clearance rate was
      paralleled by a similarly short duration of the MHC blockade effect. These in
      vivo results have implications concerning the biology of peptide-MHC
      interactions, and suggest that MHC blockade may not be feasible as a therapeutic
      approach unless effective concentrations of inhibitor can be maintained over
      extended periods of time in the extracellular fluids.

PMID- 8157956
TI  - Up-regulation of c-myc induces the gene expression of the murine homologues of
      p34cdc2 and cyclin-dependent kinase-2 in T lymphocytes.
AB  - The expression and/or up-regulation of several early T cell activation genes is
      dependent on signals transmitted through the interaction of IL-2 and IL-2R well
      before entry of the cells into S phase. In these studies, murine G0 T cells
      activated by immobilized anti-CD3 and subsequently blocked in late G1 expressed
      normal surface levels and mRNA for IL-2R alpha, IL-2R beta, and transferrin
      receptor (TfR). However, there was no expression of p34cdc2, and cyclin-dependent
      kinase (cdk)-2 was not up-regulated even in the presence of exogenous rIL-2. In
      addition the accumulation of c-myc-specific mRNA and protein was significantly
      reduced. Pretreatment of G0 T cells with c-myc antisense oligonucleotide
      effectively reduced the level of specific c-myc protein induced by activation of
      the cells by immobilized anti-CD3. The presence of antisense c-myc
      oligonucleotide inhibited the expression of cdc2 and cdk2 without affecting the
      expression of IL-2R alpha and blocked the activated T cells in the G1 phase.
      Together these studies demonstrate that c-myc regulates the expression of these
      cdk and suggest a role for c-myc in the G1/S transition.

PMID- 8157957
TI  - Differential regulation of lymphotoxin (LT), lymphotoxin-beta (LT-beta), and TNF
      alpha in murine T cell clones activated through the TCR.
AB  - The present study demonstrates differential regulation of three members of the
      TNF family, lymphotoxin (LT), LT-beta, and TNF-alpha, by activated murine T cell
      clones. We report for the first time that murine T cells transcribe LT-beta mRNA
      in the absence of any activating signal. Activation through the TCR by anti-CD3
      did not increase the accumulation of LT-beta mRNA but did increase the
      accumulation of two species of TNF-alpha mRNA and three species of LT mRNA. We
      determined that anti-CD3-activated T cells differ in their regulation of LT, LT
      beta, and TNF-alpha at the transcriptional and post-transcriptional levels. Anti
      CD3 activation resulted in substantial increases in the extent of transcription
      of the TNF-alpha and LT genes, although with different rates. LT mRNA
      accumulation was also post-transcriptionally regulated by anti-CD3. In anti-CD3
      activated T cells, the t1/2 of LT mRNA was three to four times longer than that
      of TNF-alpha mRNA. LT-beta mRNA decayed at a rate similar to that of LT mRNA. We
      also noted a dramatic difference in the cycloheximide sensitivity of LT, LT-beta,
      and TNF-alpha mRNAs. Cycloheximide superinduced the accumulation of LT mRNA, but
      not that of TNF-alpha and LT-beta mRNA, post-transcriptionally. Thus, this study
      demonstrates dramatic differences in the molecular mechanisms of regulation of
      LT, LT-beta, and TNF-alpha. It also indicates that LT production is probably the
      rate-limiting step in the formation of the LT-LT-beta complex. These differences
      suggest that the reason for the redundancy of LT, LT-beta, and TNF-alpha is their
      differential regulation rather than their functions.

PMID- 8157958
TI  - Activation of a novel serine/threonine kinase that phosphorylates c-Fos upon
      stimulation of T and B lymphocytes via antigen and cytokine receptors.
AB  - Ligation of Ag receptors in T and B lymphocytes initiates signal transduction
      cascades which alter the expression of genes that regulate cellular proliferation
      and differentiation. The transmission of signals from the membrane to the nucleus
      is mediated principally through the action of protein tyrosine and
      serine/threonine kinases. We have identified and characterized a novel
      serine/threonine kinase that phosphorylated the proto-oncogene product, c-Fos,
      and is termed Fos kinase. Fos kinase was rapidly activated after ligation of the
      CD3 and CD2 receptors in Jurkat and normal human T lymphocytes and in response to
      IL-6 and anti-IgM in the human B cell lines AF10 and Ramos, respectively. The
      phorbol ester, PMA, was also a potent inducer of Fos kinase activity in all of
      the above populations, suggesting that PKC plays a role in the regulation of this
      enzyme. Fos kinase phosphorylates c-Fos at a site near the C-terminus, as well as
      a peptide derived from this region (residues 359-370, RKGSSSNEPSSD), and Fos
      peptide competitively inhibited c-Fos phosphorylation. Fos kinase was shown to be
      distinct from other identified serine/threonine kinases, including protein kinase
      A, protein kinase C, casein kinase II, MAP kinases, p70S6K and p90RSK. Fos kinase
      was purified by anion exchange chromatography and exhibited an apparent M(r) =
      65,000 and isoelectric point = 6.1. Fos kinase may play a role in transcriptional
      regulation through its capacity to phosphorylate c-Fos at a site required for
      expression of the transcriptional transrepressive activity of this molecule.
      Moreover, its rapid activation suggests it may have a wider role within signal
      transduction cascades in lymphocytes.

PMID- 8157959
TI  - Signals for activation of CD8-dependent adhesion and costimulation in CTLs.
AB  - Adhesion of CD8+ CTL to purified class I proteins has been shown to be regulated
      by the TCR: nonactivated CTL do not adhere to immobilized class I proteins (non
      Ag), but adhesion becomes readily detectable upon treatment of the CTL with fluid
      phase anti-TCR mAb. Signals for up-regulating CD8 adhesion do not appear to
      involve products of the PI pathway, as neither increased production of inositol
      phosphates or mobilization of [Ca2+]i can be detected in response to the fluid
      phase anti-TCR mAb, but both occur when the CTL then bind to class I protein. The
      lack of a role for phosphoinositide pathway products in up-regulating CD8 was
      confirmed by the inability of phorbol ester or calcium ionophore to substitute
      for TCR mAb in triggering adhesion to class I proteins. Instead, both phorbol
      ester and calcium ionophore inhibited the anti-TCR mAb-stimulated adhesion to
      class I. Inhibitors of protein tyrosine kinases also block TCR-activated, CD8
      dependent adhesion to class I, and concomitantly block inositol phosphate
      release, Ca2+ mobilization and degranulation. Inhibition of signaling and
      response does not appear to be caused solely by the inhibition of adhesion to
      class I, however, because these inhibitors also block signaling in response to
      immobilized anti-TCR mAb under conditions in which binding of other receptors to
      their ligands is not necessary to initiate phosphoinositide hydrolysis and
      degranulation. These results lend further support for a model in which CTL
      activation involves a cascade of adhesion and signaling events initiated by the
      TCR and propagated by CD8 and additional cell-surface receptors.

PMID- 8157960
TI  - A mutation of the mu transmembrane that disrupts endoplasmic reticulum retention.
      Effects on association with accessory proteins and signal transduction.
AB  - The mu heavy chain has an unusually high content of hydroxyl-containing amino
      acids in its membrane-spanning region. We have examined the involvement of two of
      these hydrophilic residues in endoplasmic reticulum (ER) retention, interactions
      with Ig-alpha/Ig-beta, and transmembrane signaling. Neighboring tyrosine and
      serine residues were mutated to either phenylalanine and alanine (mutant YS/FA)
      or valine and valine (mutant YS/VV). Membrane Ig (mIgM) molecules containing
      these mutant mu chains were expressed on the surface of transfected B lymphoma
      cells. Anti-Ig-induced signaling by the YS/FA mutant mIgM was equivalent to wild
      type (wt) mIgM, whereas signaling by the YS/VV mutant mIgM was notably
      diminished. Association between mutant YS/VV mIgM and Ig-alpha/Ig-beta was
      detectable but reduced in comparison to YS/FA or wt mIgM. Signaling by YS/VV
      mutant mIgM appeared to involve Ig-alpha/Ig-beta, because these proteins were
      tyrosine phosphorylated on receptor cross-linking. When YS/VV and wt mu chains
      were cotransfected with light chains into nonlymphoid cells, mutant mIgM was
      expressed at the cell surface in the absence of Ig-alpha/Ig-beta, whereas wt mIgM
      was not. These data suggest that the mutated residues contribute to ER retention
      and directly or indirectly to association with Ig-alpha/Ig-beta. Moreover, ER
      retention can be disrupted without preventing functional association with Ig
      alpha/Ig-beta. In addition, these data indicate that the hydroxyl groups of the
      mutated residues are not required for functional association between mu and Ig
      alpha/Ig-beta because their removal did not reduce the ability of the YS/FA
      mutant mIgM to associate with accessory proteins or to participate in signal
      transduction.

PMID- 8157961
TI  - Acute rejection of marrow grafts in mice. Dependence on and independence of
      functional TCR in the rejection process.
AB  - The question of how irradiated mice acutely reject marrow grafts has remained
      controversial, and evidence in support of T cell- and natural killer cell
      mediated rejection mechanisms has been provided. Here we show in support of
      previous data that CB17 severe combined immunodeficiency mice acutely reject
      allogeneic marrow but the specificity of rejection cannot be mapped within the
      MHC. It is shown that a similar rejection specificity is also expressed in normal
      CB17 mice and that it is caused by CD3- or CD3+ effector cells that do not
      utilize TCR. In search of TCR-independent rejection mechanisms in other mouse
      strains, use is made of TCR transgenic mice expressing a defect in recognizing H
      2Dd. It is shown that, although marrow graft rejection is impaired in these mice,
      pointing to participation of TCR in the rejection process, residual resistance
      does exist. This resistance maps to the MHC, cannot be shown to involve TCR, and
      appears to be expressed by NK1+ CD3+ cells. It is concluded that acute marrow
      graft rejection in normal mice can be mediated by both TCR-mediated and NK cell
      receptor-dependent effector mechanisms, depending on the particular mouse
      strains.

PMID- 8157962
TI  - The NF-beta A-binding element, not an overlapping NF-IL-6-binding element, is
      required for maximal IL-1 beta gene expression.
AB  - NF-beta A is a monocyte, neutrophil, and B cell-specific nuclear protein that is
      involved in regulation of the IL-1 beta gene. These studies further define the
      functional role of NF-beta A in RAW264.7 monocytic cells by using transient
      transfection analysis. We showed that NF-beta A was able to activate
      transcription from a heterologous promoter in a distance-independent and dose
      dependent manner. NF-beta A also appeared to function in a positionally
      independent manner within the IL-1 beta cap-site proximal (CSP) promoter. NF-beta
      A was required for maximal IL-1 beta gene expression directed by the upstream LPS
      inducible enhancer element. Deletion of the NF-beta A-binding sequence resulted
      in an 80% reduction in basal reporter gene activity and an 86% reduction in LPS
      inducible reporter gene activity in constructs containing only the enhancer and
      CSP promoter. Other regulatory elements located between the enhancer and the cap
      site were not able to substitute functionally for the absence of NF-beta A.
      Recently, other investigators have reported that IL-1 beta CSP promoter function
      was decreased by introducing multiple mutations within both the NF-beta A-binding
      sequence, and a putative overlapping NF-IL-6-binding sequence. We have found that
      these mutations predominantly affect NF-beta A binding. Furthermore NF-beta A,
      and not NF-IL-6, was required for supporting basal and LPS-inducible
      transcription from a minimal IL-1 beta CSP promoter (positions -58 to +11). This
      promoter region did not appear to direct monocyte-specific IL-1 beta gene
      expression because reporter constructs containing the IL-1 beta CSP promoter were
      also active in transiently transfected HeLa cells.

PMID- 8157963
TI  - The origin of the primate Mhc-DRB genes and allelic lineages as deduced from the
      study of prosimians.
AB  - MHC class II genes of the DRB family were partially sequenced from 10 individuals
      representing six species of prosimians: Galago senegalensis, G. moholi, Otolemur
      garnetti, Loris tardigradus, Petterus (Lemur) fulvus, and Lemur catta.
      Altogether, 41 different genes were discerned, all distinct from genes identified
      previously. Comparative analysis of the sequences has led to the following
      conclusions. First, the DRB loci present in human populations diverged from one
      another before the divergence of prosimian and anthropoid primates. Second, major
      allelic lineages of the DRB1 locus, such as DRB1*03 (DRB1*13) and DRB1*04, were
      established more than 85 million years ago. Third, the DRB6 gene was inactivated
      before the separation of prosimians and anthropoids, and has remained a
      pseudogene for more than 85 million years. Fourth, the primate DRB region is
      structurally and functionally unstable. In Lemur catta, for example, all DRB
      genes have apparently been lost and their function taken over by DOB and/or DPB
      genes. DRB genes are, however, present in a related species, Petterus (Lemur)
      fulvus. Fifth, the prosimian DRB3 genes are all inactive; their function seems to
      have been taken over by new genes. Sixth, several of the prosimian DRB genes and
      pseudogenes have recently been duplicated. In Otolemur garnetti, for example, one
      chromosome carries at least three copies of the DRB3 pseudogene.

PMID- 8157964
TI  - An isotype switched and somatically mutated rheumatoid factor clone isolated from
      a MRL-lpr/lpr mouse exhibits limited intraclonal affinity maturation.
AB  - Employing site-directed mutagenesis we have reconstructed and expressed the germ
      line precursor of an expanded rheumatoid factor (RF) clone. This RF clone,
      designated clone F, was isolated from an autoimmune MRL/MpJ-lpr/lpr mouse. Most
      of the clone members were extensively mutated and isotyped-switched. The
      predominant isotype of clone F was gamma 3. The RF bound specifically to the MRL
      gamma 2 a allotype (Igh-1j) but not to the B6 gamma 2a allotype (Igh-1b). The
      germ-line antibody was also found to bind gamma 2a in an RF assay. The affinities
      of the germ-line RF and representative members of the clone were measured in an
      ELISA-based equilibrium binding assay. The dissociation constant (Kd) of the germ
      line RF was 2.5 x 10(-6) M. All of the expressed clone members had affinities
      within a two- to sixfold range of the germ line, indicating that the mechanisms
      of somatic hypermutation and selection resulted in only limited affinity
      maturation of this autoantibody clone.

PMID- 8157965
TI  - Isolation and characterization of the Xenopus terminal deoxynucleotidyl
      transferase.
AB  - A cDNA clone containing the sequence of the Xenopus homologue of terminal
      deoxynucleotidyl transferase (TdT) was isolated and analyzed. The derived amino
      acid sequence shares > 50% identity with the human, mouse, and bovine TdT
      sequences. By hybridization and PCR analyses Xenopus TdT mRNA was found in the
      thymus and not in the spleen, kidney, intestine, or liver. During ontogeny TdT
      appears in significant amounts in the thymus of tadpoles at metamorphic climax
      but little in the earlier midlarval stages. The emergence of TdT only late in
      development correlates with the paucity of N region addition in larval Ig heavy
      chain sequences. Past experiments on the ontogeny of the Xenopus immune system
      revealed a less efficacious tadpole immune response in skin graft rejection and
      Ab heterogeneity; the absence of TdT in the tadpole stages fits well with the
      notion of lower larval TCR and Ab diversity.

PMID- 8157966
TI  - Cloning of two adenosine receptor subtypes from mouse bone marrow-derived mast
      cells.
AB  - Adenosine potentiates the stimulated release of mast cell mediators.
      Pharmacologic studies suggest the presence of two adenosine receptors, one
      positively coupled to adenylate cyclase and the other coupled to phospholipase C
      activation. To identify mast cell adenosine receptor subtypes, cDNAs for the A1
      and A2a adenosine receptors were obtained by screening a mouse brain cDNA library
      with the use of PCR-derived probes. Mouse bone marrow-derived mast cell cDNA
      libraries were constructed and screened with the use of A1 and A2a cDNA probes,
      which revealed the presence of A2a, but not A1, receptor clones. A putative A2b
      receptor was identified by using low stringency mast cell library screening.
      Northern blotting of mast cell poly(A)+ RNA with the use of receptor subtype
      probes labeled single mRNA bands of 2.4 kb and 1.8 kb for the A2a and A2b
      receptors, respectively. In situ cells. An A2a receptor-specific agonist failed
      to enhance mast cell mediator release, which suggests that the secretory process
      is modulated through the A2b and/or another receptor subtype. By using RNase
      protection assays, we found that mast cells that had been cultured in the
      presence of N-ethylcarboxamidoadenosine for 24 h exhibited a decrease in both A2a
      and A2b receptor RNA levels. Cells that had been cultured for 1 to 2 days in the
      presence of dexamethasone demonstrated increased amounts of A2a receptor mRNA,
      but no identifiable change in A2b receptor mRNA. Mast cells possess at least two
      adenosine receptor subtypes that may be differentially regulated.

PMID- 8157967
TI  - A disease-related epitope of Torpedo acetylcholine receptor. Residues involved in
      I-Ab binding, self-nonself discrimination, and TCR antagonism.
AB  - Residues 146-162 of the Torpedo californica acetylcholine receptor alpha-subunit
      contain the immunodominant T cell epitope for experimental autoimmune myasthenia
      gravis-susceptible C57BL/6 mice. To develop potential therapeutic peptides, a
      detailed analysis of the epitope was undertaken. Truncated and substituted
      synthetic peptides were tested as stimulators of T cell clones and immune lymph
      node cells. Critical residues spanned positions 151-159. Y151 and V156 were
      critical for MHC binding. The results indicated a general motif for binding to I
      Ab to be an aromatic or hydrophobic residue (preferentially Y or F) at position i
      followed by an uncharged residue at position (i + 5). Lysine was not tolerated at
      position (i + 8). Residues D152, K155, S157, and I158 were important T cell
      contact residues. A peptide corresponding to the murine 146-162 sequence, which
      differs from the Torpedo sequence at 5 residues, bound to I-Ab but was
      nonimmunogenic, consistent with the assigned TCR and I-Ab contact residues. These
      results suggest that tolerance is responsible for the lack of T cell cross
      reactivity with the murine acetylcholine receptor. Substituted peptides were
      tested for the inhibition of T cell clone responses and for TCR antagonism.
      Although peptides substituted at residues 157 and 158 inhibited most clones, no
      single peptide could completely inhibit all clones or primed lymph node cells.
      These findings indicate that antagonist peptides may be useful in inhibiting T
      cell responses to complex Ag displaying a single immunodominant epitope. Multiple
      antagonists used in combination may be required for maximum inhibition of the
      response.

PMID- 8157968
TI  - Effects of human class I transgenes on Toxoplasma gondii cyst formation.
AB  - MHC class I genes are important in the regulation of cyst number in mice
      perorally infected with Toxoplasma gondii. Since human MHC class I molecules may
      be capable of functioning as restriction elements in mice, to determine whether
      class I genes also control outcome of T. gondii infection for humans, a
      transgenic mouse model was developed using human class I genes in mice. Human HLA
      B27 and Cw3 transgenic mice, with the cyst-susceptible B10 mouse background, were
      tested for resistance to cyst formation after peroral infection with the Me49
      strain of T. gondii. Introduction of the B27 gene into susceptible mice made them
      even more susceptible to T. gondii brain cyst formation. In contrast, HLA-DB27
      transgenic mice that have a substitution of the alpha 3 portion of the human
      class I molecule with the alpha 3 portion of the mouse Kd molecule had the same
      number of brain cysts as susceptible B10 control mice when perorally infected.
      Similarly, HLA-Cw3 transgenic mice had the same number of brain cysts as the
      susceptible B10 controls. These results indicate that the interaction between CD8
      on mouse T cells and the human class I molecule in transgenic mice does not
      always occur, and sometimes may hinder a normal response. Furthermore, B27 and
      Cw3 transgenes did not generate resistance to cyst formation in infection by T.
      gondii.

PMID- 8157969
TI  - The resolution of acute malaria in a definitive model of B cell deficiency, the
      JHD mouse.
AB  - Because the role of cell-mediated immunity (CMI) in the resolution of blood-stage
      malaria remains unclear, we examined the question of whether mice completely
      lacking Ab-mediated immunity (AMI) but possessing some CMI can resolve
      experimental malaria previously reported not to require AMI for resolution.
      Severe combined immunodeficient mice reconstituted with enriched immune T cells
      (< 0.5% B220+ cells) suppressed acute Plasmodium chabaudi adami parasitemia,
      suggesting that T, but not B, cells are required to clear this form of malaria.
      In addition, JHD mice, which are a definitive model of B cell deficiency, were
      also shown to resolve P. chabaudi adami, Plasmodium vinckei petteri and
      Plasmodium chabaudi chabaudi malaria. These observations collectively establish
      that CMI alone can mediate the clearance of acute malaria caused by these
      subspecies of Plasmodium. Moreover, the protective cell-mediated immune response
      involved depends upon CD4+ T cells because JHD mice treated with anti-CD4 mAb do
      not resolve their infections. These results suggest that evaluation of
      immunization regimens to activate CD4+ T cell dependent cell mediated immunity
      against Plasmodium falciparum may be appropriate.

PMID- 8157970
TI  - Mast cells augment lesion size and persistence during experimental Leishmania
      major infection in the mouse.
AB  - Mast cells are a source of a variety of cytokines that may influence the host
      response to Leishmania major. To investigate the role of mast cells during L.
      major infection, we performed a morphometric analysis of mast cells at cutaneous
      sites in resistant C57BL/6 mice and susceptible BALB/c mice injected with L.
      major. Extensive dermal mast cell degranulation was found at sites of L. major
      infection in both strains of mice. We also examined the course of L. major
      infection in genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice,
      their respective congenic normal (WBB6F1-(+/+) or WCB6F1-(+/+)) littermates, and
      WBB6F1-W/Wv mice that had been selectively and locally repaired of their
      cutaneous mast cell deficiency. We found that mast cells significantly augmented
      the intensity and maximal size of the cutaneous lesions at sites of L. major
      infection, and in some cases substantially prolonged the persistence of the
      reactions. However, the lesions ultimately resolved in both the mast cell
      deficient and the congenic normal mice. In addition, the presence or absence of
      mast cells had little or no effect on the numbers of viable parasites recovered
      from the cutaneous lesions. Moreover, mast cell-deficient W/Wv mice and the
      congenic normal (+/+) mice produced similar levels of IFN-gamma mRNA in lymph
      nodes draining the cutaneous lesions whereas no IL-4 mRNA was detectable. Taken
      together, these data suggest that mast cells significantly augment the size of
      cutaneous lesions during L. major infection in mice. However, mast cells do not
      appear to influence significantly either the parasite burden or the ultimate
      resolution of the infection.

PMID- 8157971
TI  - Isolation of neutralizing anti-C5a monoclonal antibodies from a filamentous phage
      monovalent Fab display library.
AB  - A panel of mAbs against the activated complement component C5a was obtained from
      a filamentous phage M13-Fab display library generated from mice immunized with
      human rC5a. Fabs isolated from the library after iterative selection vs rC5a
      bound to both rC5a and purified C5. To isolate Fabs specific for neoepitopes
      expressed on C5a but not on the native complement component C5 the library was
      rescreened in a competitive manner. The phage Fab library was first incubated
      with immobilized C5 to deplete C5 reactive Fabs. The C5 nonadherent phage were
      then incubated with immobilized rC5a in the presence of soluble C5. Bound phage
      were eluted and subjected to two additional cycles of subtraction with
      immobilized C5 and selection with immobilized rC5a in the presence of soluble C5.
      After three cycles of this competitive biopanning four Fabs reactive with rC5a
      were isolated. Two bound preferentially with and neutralized C5a. Competitive
      biopanning of phage display libraries may increase the probability of
      identification of Abs of the desired specificity.

PMID- 8157972
TI  - Eosinophil transendothelial migration induced by cytokines. II. Potentiation of
      eosinophil transendothelial migration by eosinophil-active cytokines.
AB  - Activation of HUVEC monolayers by IL-1 beta or TNF-alpha induces migration of
      eosinophils across the endothelial monolayer (i.e., transendothelial migration)
      in vitro. In the present study, we demonstrate that culture of freshly isolated
      eosinophils in the presence of IL-5 for 24 to 48 h before use in the assay
      dramatically potentiated CD18-dependent eosinophil transendothelial migration
      through unstimulated endothelial monolayers. Granulocyte macrophage (GM)-CSF
      induced eosinophil transendothelial migration but did not induce neutrophil
      transendothelial migration. When IL-1 beta-activated endothelial cells were used,
      GM-CSF, IL-3, or IL-5 caused only modest potentiation of eosinophil
      transendothelial migration. Since activated endothelial cells are known to
      produce GM-CSF, we hypothesized that endothelial-derived GM-CSF might play a role
      in the process of IL-1 beta-induced eosinophil transendothelial migration. IL-1
      beta-activated endothelial monolayers grown on the permeable supports produced
      0.3 +/- 0.1 ng/ml of GM-CSF during a 4-h incubation and neutralizing Ab against
      GM-CSF inhibited eosinophil transendothelial migration by 48%, suggesting that
      endothelial-derived GM-CSF may participate in the response. Eosinophils purified
      from bronchoalveolar lavage 18 to 20 h after experimental Ag challenge in the
      lungs of allergic volunteers showed enhanced transendothelial migration,
      indicating that the cells may have undergone cytokine activation in vivo.
      Eosinophil-active cytokines may contribute to the preferential accumulation of
      eosinophils in vivo in part via potentiation of eosinophil transendothelial
      migration.

PMID- 8157974
TI  - Proteinase 3. A neutrophil proteinase with activity on platelets.
AB  - Purified proteinase 3 (PR3) devoid of any elastase (HLE) and cathepsin G (Cat.G)
      contaminants, was prepared from azurophilic granules of human polymorphonuclear
      neutrophils by using a novel procedure. Although unable to induce platelet
      activation (up to 25 micrograms/ml) by itself, PR3 at a concentration as low as
      2.5 micrograms/ml enhanced the platelet response to a concomitantly added
      threshold concentration of Cat.G, a recognized platelet agonist. In the presence
      of 10 micrograms/ml PR3, aggregation and degranulation of platelets induced by
      Cat.G were 43.2 +/- 5.9% and 27.1 +/- 1.9% as compared with 5.5 +/- 2.9% and 4.2
      +/- 1.5% (n = 4) for Cat.G alone. This enhancing effect by PR3 was also observed
      with collagen and a cyclic endoperoxide analogue, and was inhibited by eglin C
      and elafin, two PR3 inhibitors. Associated with the removal of activity by a anti
      PR3 mAb and the lack of effect of the secretory leukocyte proteinase inhibitor,
      these data demonstrated that the effect is specifically related to the enzymatic
      activity of PR3. It is hypothesized that this mechanism could play a role in the
      polymorphonuclear neutrophil-mediated platelet activation, an event already known
      to be dependent on Cat.G and HLE. This is supported by the fact that the
      association of PR3 and HLE, at concentrations ineffective by themselves, was able
      to potentiate Cat.G-induced platelet activation.

PMID- 8157973
TI  - Fc gamma receptor cross-linking down-regulates IL-1 receptor antagonist and
      induces IL-1 beta in mononuclear phagocytes stimulated with endotoxin or
      Staphylococcus aureus.
AB  - The cross-linking of monocyte Fc gamma R is a potent stimulus for IL-1ra
      production but does not induce IL-1 beta. However, during systemic infection, IgG
      coated bacteria can activate mononuclear phagocytes via both cell wall components
      and opsonized IgG. Therefore, we analyzed the effect of combinations of Fc gamma
      R cross-linking and bacterial cell wall components on mononuclear phagocyte IL-1
      beta and IL-1ra production. Human mononuclear cells and monocytes were cultured
      either alone or with combinations of immobilized IgG, LPS, or heat-killed
      Staphylococcus aureus (HKSA). Cells cultured on immobilized IgG released large
      amounts of IL-1ra but no detectable IL-1 beta. In response to LPS, mononuclear
      cells released IL-1ra at 1000-fold lower doses of LPS than was required to induce
      IL-1 beta. However, when measured in the presence of immobilized IgG, the LPS
      sensitivity for IL-1 beta release increased 100-fold, whereas IL-1ra release
      correlated inversely with the LPS dose. Furthermore, HKSA, a nonendotoxin
      stimulus, affected mononuclear cell IL-1 beta and IL-1ra release similarly. In
      addition, polymyxin B, a specific endotoxin inhibitor, blocked the LPS, but not
      the HKSA-induced changes in IL-1 beta and IL-1ra secretion, irrespective of
      immobilized IgG co-stimulation. In summary, these results suggest that
      mononuclear phagocyte stimulation with immobilized IgG favors IL-1ra over IL-1
      beta production. Conversely, the addition of LPS or HKSA to the Fc gamma R
      stimulated cells augments IL-1 beta but suppresses IL-1ra production.

PMID- 8157975
TI  - Action and target cell specificity of human macrophage-stimulating protein (MSP).
AB  - Macrophage-stimulating protein (MSP) induces mouse resident peritoneal
      macrophages to become responsive to the chemoattractant C5a and to ingest C3bi
      coated erythrocytes. We now show that MSP action is not limited to complement
      induced responses, because it also induced responsiveness to the noncomplement
      chemoattractant casein. In addition to stimulating responsiveness to attractants,
      MSP functioned alone as a chemoattractant for resident peritoneal macrophages,
      with an optimal concentration of approximately 0.2 nM. A critical difference
      between MSP and C5a is that resident macrophages did not migrate to C5a without
      an additional stimulus such as MSP in the cell suspension, whereas macrophages
      suspended in medium alone migrated to MSP in the attractant well. Thus, in
      contrast to C5a, MSP seems capable of a dual role, both activator and attractant.
      MSP had no effect on responsiveness of mouse peritoneal exudate macrophages to
      C5a; nor could it attract exudate macrophages or human blood monocytes.
      Absorption studies showed that resident macrophages have a receptor for MSP, but
      exudate macrophages do not. In view of these findings, it seems that the
      biological role of MSP is not as a recruiter of blood monocytes to sites of
      inflammation, but as an activator of mature macrophages. The MSP-induced
      activated state for responsiveness to C5a or C3bi was transient, and decayed at a
      first order rate with a t 1/2 of approximately 1 h. This is a new example of the
      transience of activation induced in macrophages by proinflammatory stimuli.

PMID- 8157976
TI  - Complement component C7. Assessment of in vivo synthesis after liver
      transplantation reveals that hepatocytes do not synthesize the majority of human
      C7.
AB  - C7 M/N typing, the determination of the allotypes of the recently described C7
      M/N protein polymorphism, was conducted on serum samples from donors and
      recipients of 100 liver transplantations to determine whether the liver is the
      predominant site of in vivo synthesis of human complement protein C7. Twenty-one
      cases were informative as the recipient was transplanted with the liver obtained
      from a donor with a different C7 M/N allotype. The determination of the C7 levels
      and phenotypes of up to 10 post-transplantation (p.t.) samples revealed that
      there was at most only a 50% contribution of the transplanted liver toward the C7
      M/N allotype at 2 to 3 wk p.t.; that influence decreased with time and was
      approximately 10% in the samples obtained later than 6 wk after transplantation.
      C7 is thus the only terminal complement component not predominantly synthesized
      by hepatocytes, which is compatible with the observation that C7 is not an acute
      phase reactant. The transient contribution of the donor phenotype appears to be
      attributable to cells of the mononuclear phagocyte lineage, Kupffer cells in
      particular that are replaced by cells of recipient origin. Various cells of that
      lineage that are known to synthesize C7 in vitro, therefore, contribute more
      toward the C7 concentration than previously anticipated. Enhanced local C7
      synthesis at the site of inflammation might add further to the basic C7 level
      especially because C7 is often the limiting factor for terminal complement
      complex generation.

PMID- 8157977
TI  - Physical association of complement receptor type 3 and urokinase-type plasminogen
      activator receptor in neutrophil membranes.
AB  - A previous study has shown that Fc gamma RIIIB (CD16), an extensively
      glycosylated glycosyl-phosphatidylinositol-linked neutrophil membrane protein,
      specifically co-caps with the iC3b R (CR3; CD11b/CD18). This study tests the
      possible physical interactions of another extensively glycosylated glycosyl
      phosphatidylinositol-linked protein, the urokinase-type plasminogen activator
      receptor (uPAR), with CR3. Receptors were labeled using fluorochrome-conjugated
      F(ab')2 fragments of an anti-CR3 mAb. In some cases cells were capped using
      second step F(ab')2 fragments of an anti-mouse F(ab')2 antiserum. After 30 min at
      37 degrees C, 65 +/- 4% of the cells exhibited CR3 caps whereas 61 +/- 2%
      demonstrated uPAR caps. When CR3-capped cells were probed with F(ab')2 fragments
      of anti-uPAR conjugated to a distinct fluorochrome, 45 +/- 3% of the cells co
      capped uPAR. When uPAR was capped, 48 +/- 2% of the cells co-capped CR3. Similar
      levels of co-capping were observed using a DNP-conjugated anti-CR3 F(ab')2 and an
      anti-DNP second step F(ab')2 reagent for capping or using FITC-uPA as a probing
      reagent. Furthermore, CR3-uPAR co-capping and/or co-clustering was also observed
      using anti-CR3 IgM and Mn2+ as integrin aggregation stimuli. Significant co
      capping of anti-CD14, anti-CD59, anti-Mo5, anti-HLA, or NBD-PE (a lipid probe)
      was not observed. Moreover, CR3 and uPAR co-capping was blocked by N-acetyl-D
      glucosamine, but not by six other saccharides, suggesting that a lectin-like site
      may participate in co-capping. This suggests that CR3 may regulate adhesive
      events by several mechanisms, including the regulation of the spatial
      distribution of uPAR.

PMID- 8157978
TI  - Serum IgA-mediated neutralization of HIV type 1.
AB  - The sera of 33 HIV-1-infected individuals, previously shown to neutralize HIV-1MN
      in vitro, were screened by ELISA for IgA reactivity against rgp120MN and a
      synthetic V3MN loop peptide. Six were selected for evaluation of the effect of
      serum IgA from infected individuals on the in vitro infection of susceptible
      target cells by HIV-1MN. By using protein G immobilized on Sepharose, we depleted
      the sera of IgG to a level undetectable by nephelometry and viral envelope
      specific ELISA. The IgA component of the IgG-depleted serum was affinity purified
      with immobilized jacalin, a lectin that selectively binds the IgA1 fraction of
      human Ig. IgG-depleted sera and purified IgA1 serum fractions showing IgA
      reactivity against rgp120MN and V3MN by ELISA inhibited the in vitro infection of
      CEM-ss cells by HIV-1MN, but sera depleted of both IgG and IgA1 did not. These
      data show that, like serum IgG, serum IgA from selected HIV-1-infected
      individuals is capable of neutralizing HIV-1MN in vitro. The biologic
      significance of this observation and the identities of serum IgA-recognized HIV-1
      neutralization epitopes remain to be determined.

PMID- 8157979
TI  - Oral tolerance in humans. T cell but not B cell tolerance after antigen feeding.
AB  - The purpose of this study was to investigate whether oral tolerance, defined as
      Ag-specific immunologic unresponsiveness after Ag feeding, could be induced in
      humans after prolonged Ag ingestion. Eight adult volunteers ingested a total dose
      of 0.5 g of keyhole limpet hemocyanin (KLH) followed by subcutaneous immunization
      with KLH. Eight controls received only the subcutaneous immunization. In the
      group fed KLH, there was a significant reduction in KLH-specific T cell
      proliferation (p = 0.04) and delayed skin test responses (p = 0.07) to KLH. KLH
      ingestion alone did not induce significant levels of Abs in either serum or
      secretions. However, after the subsequent subcutaneous immunization, the number
      of circulating IgG and IgM anti-KLH-producing cells, the titers of serum IgG,
      IgA, and IgM anti-KLH Abs, and the titers of IgA anti-KLH Abs in saliva and
      intestinal secretions were significantly greater in the KLH-fed group than in the
      nonfed group. We conclude that KLH feeding induced systemic T cell tolerance, but
      B cell priming, at both systemic and mucosal sites. These studies support the
      concept of using Ag feeding as a treatment for certain immune-mediated diseases.

PMID- 8157980
TI  - Functional and phenotypic change of T cells in murine acquired immune deficiency.
AB  - Infection of susceptible C57BL/6 mice with defective LP-BM5 murine leukemia virus
      causes disease termed murine acquired immune deficiency syndrome (MAIDS). The
      disease is characterized by lymphoadenopathy, hyperimmunoglobulinemia, and immune
      deficiency in both T and B cell functions. The development of disease requires
      the presence of mature T cells, especially CD4 T cells, and B cells. It has
      previously been shown that a B cell tumor line derived from MAIDS mouse
      stimulated a large fraction of unprimed T cells based on TCR V beta chain
      expression. This stimulatory activity was assumed to be mediated by a
      superantigen encoded by MAIDS virus. The stimulation of T cells by viral
      superantigen was thought to play a role in the development of the disease. To
      examine the role of T cell reactivity to MAIDS superantigen, we used TCR
      transgenic mice. There are two distinct T cell populations which can be
      distinguished based on their TCR expression and function in the TCR transgenic
      mice, one bearing the transgene derived alpha- and beta-chain TCR that is
      nonreactive to MAIDS superantigen and the other bearing an endogenous alpha- but
      transgene-derived beta-chain TCR that is reactive to superantigen. Unlike T cells
      found in noninfected TCR transgenic mice, anergic T cells expanding in virally
      infected TCR transgenic mice are homogeneous for the TCR phenotype, indicating
      the presence of a selection of T cells based on their TCR expression. T cell
      hybridomas established by fusing T cells from virus-infected transgenic mice to
      thymoma cell line are also anergic. We found mRNA of defective LP-BM5 virus in a
      majority of T cell hybridomas from virus-infected mice but not from noninfected
      mice. By using in vitro infection of T cell clones with recombinant virus
      containing LP-BM5 MAIDS virus gag gene, we have demonstrated that virus infection
      directly abrogated the Ag-specific reactivity of T cells. The establishment of
      anergic T cell hybridomas and the in vitro infection of T cells with recombinant
      viruses would be a useful tool in the analysis of biochemical and molecular
      mechanisms of T cell dysfunction in MAIDS.

PMID- 8157981
TI  - A single amino acid substitution in core residues of S-antigen prevents
      experimental autoimmune uveitis.
AB  - We have previously reported that microbial Ags, having a three- to six-amino-acid
      sequence homology with a uveitopathogenic epitope (peptide M) of retinal soluble
      protein (S-Ag), induce experimental autoimmune uveitis (EAU). Another
      uveitopathogenic epitope (peptide G) of S-Ag also was characterized. In addition,
      we have characterized the core sequences by truncating peptides G and M from
      amino acid and carboxyl termini. In this study, we have further defined the core
      sequences using synthetic octapeptides with a single amino acid substitution. In
      addition, the analogues of peptides Gm5 or Mm4 are capable of inhibiting the
      proliferative response of T-lymphocytes from rats immunized with peptides G-8 or
      M-8, respectively. Co-injection of a pathogenic peptide with nonpathogenic
      substitution analogues blocked the induction of EAU. These results suggest that
      specific nonpathogenic analogues with single amino acid substitution derived from
      pathogenic peptides have potential for prevention and therapy of autoimmune
      diseases.

PMID- 8157982
TI  - Epitopes on proteinase-3 recognized by antibodies from patients with Wegener's
      granulomatosis.
AB  - The 228 amino acid primary sequence of proteinase-3 (PR3) was studied for
      antigenic epitopes, which react with IgG Ab in sera of patients with Wegener's
      granulomatosis, by synthesizing overlapping 7 mers of PR3 linear sequence on
      pins. Main regions of linear sequence reactivity included GHEAQPH (at residues 4
      10), QPHSRPY (8-14), TQEPTQQ (65-71), ATVQLPQ (108-114), QLPQQDQ (111-117),
      PVPHGTQ (118-124), RVGAHDP (132-138), FCRPHNI (154-160), PRRKAGI (165-171),
      FGDSGGP (173-179), and IDSFVIW (189-195). All of these regions were surface
      accessible and seemed to be on the outside of the molecule. By substituting a
      glycine or an alanine for each residue within each reactive epitope, we
      identified the arginine at 12, valine at 119, proline at 120, histidine at 121,
      arginine at 132, alanine at 135, histidine at 136, and glycine at 178 as major
      immunodominant single residues that contribute to antigenic determinants.
      Visualization of these reactive regions on a three-dimensional computer-generated
      carbon PR3 trace diagram showed that one aspect of the molecule on the
      inferolateral surface comprised most of the antigenic regions. Two peptides,
      ATVQLPQ and RVGAHDP, when preincubated with Wegener's granulomatosis sera,
      produced almost complete inhibition of Wegener's granulomatosis IgG Abs either
      binding to PR3 on the ELISA plate or by reacting with polymorphonuclear leukocyte
      azurophilic granules in immunofluorescence assays for cANCA. FGDSGGP (at residues
      173-179), one epitope that was recognized by Wegener's patient sera Abs, included
      part of the active catalytic triad for PR3. Rabbit Abs against the PR3 peptides
      ATVQLPQ or RVGAHDP showed a cANCA cytoplasmic granular pattern of
      immunofluorescence staining when they were incubated with polymorphonuclear
      leukocytes. These findings indicate that it is possible to identify various
      antigenic sites on PR3 by using overlapping 7 mers of portions of the solvent,
      accessible linear sequence.

PMID- 8157983
TI  - International collaborative study of the candidate international standards for
      human tumour necrosis factors alpha (hTNF-alpha) and beta (hTNF-beta) and for
      murine tumour necrosis factor alpha (mTNF-alpha).
AB  - Four ampouled preparations of human tumour necrosis factor alpha (hTNF-alpha),
      one ampoule of human tumour necrosis factor beta (hTNF-beta) and one ampoule of
      mouse tumour necrosis factor alpha (mTNF-alpha) were evaluated by 20 laboratories
      in nine countries for their suitability to serve as international standards for
      these materials. A further three preparations of recombinant hTNF-alpha were
      included in the study so that hTNF-alpha preparations from different sources and
      with various structures could be compared. The preparations were assayed using in
      vitro bioassays and immunoassays. On the basis of the results reported here, with
      the agreement of participants in the study and with the authorisation of the
      Expert Committee on Biological Standardization (ECBS) of the World Health
      Organization (WHO), the preparation of hTNF-alpha in ampoules designated 87/650
      was established as the international standard for hTNF-alpha with a defined
      potency of 40,000 international units per ampoule. Estimates relative to hTNF
      alpha for both hTNF-beta and mTNF-alpha showed a substantial inter-laboratory
      variability in cytotoxic activity indicating that no preparations of hTNF-alpha
      would be suitable as a reference standard for either hTNF-beta or mTNF-alpha.
      However, given the current need for reference preparations for these materials,
      the ampouled preparations of hTNF-beta (87/640) and mTNF-alpha (88/532) were
      assigned potencies in arbitrary units and are available as reference reagents.

PMID- 8157984
TI  - A new flow cytometric assay for the evaluation of phagocytosis and the oxidative
      burst in whole blood.
AB  - Phagocytes play an important role in host defence against microorganisms and
      different techniques are needed to evaluate their functional activities. Here we
      describe a rapid, simple and reliable one step procedure to measure the
      phagocytosis rate and oxidative burst activation of both polymorphonuclear
      leukocytes (PMN) and monocytes, by means of flow cytometry using only small
      quantities of whole blood. The two species of bacteria employed as test
      microorganisms, Staphylococcus aureus and Candida albicans showed a somewhat
      different behaviour. We found that the present method could be used as an
      alternative test in the diagnosis of chronic granulomatous disease (CGD).
      Moreover we were able to analyse, in a one step procedure, defective phagocyte
      functions in a group of paediatric patients suffering from recurrent microbial
      infections.

PMID- 8157985
TI  - Monoclonal antibody based enzyme-linked and chemiluminescent assays for the human
      interleukin-1 receptor antagonist. Application to measure hIL-1ra levels in
      monocyte cultures and synovial fluids.
AB  - Interleukin-1 receptor antagonist (IL-1ra) has the potential to counteract at
      least part of the biological effects of interleukin-1. The outcome of an
      inflammatory reaction may therefore be determined by the balance between IL-1 and
      IL-1ra, rather than by IL-1 alone. We have developed an immunoassay to address
      this issue as well as to assess the effects of anti-inflammatory agents on the
      expression of IL-1 and IL-1ra in vitro or in body fluids. Recombinant human IL
      1ra was expressed in an E. coli system, purified to homogeneity, and used to
      derive monoclonal antibodies in mice as well as polyclonal antibodies in rabbits.
      A sandwich ELISA was constructed with F(ab')2 fragments of a high affinity
      monoclonal antibody and the rabbit serum as a source of secondary antibody. The
      assay required no sample treatment to avoid interference by rheumatoid factor.
      The measuring range was 0.020-2 ng/ml. By labelling a second monoclonal antibody
      with an acridinium ester, a chemiluminescence assay with a wider measuring range
      (0.050-15 ng/ml) was generated. In accord with published data, we found that IL
      1ra was secreted by human monocytes stimulated with LPS, Zymosan, IL-1 alpha, or
      human IgG. After an induction phase of ca. 4 hours and depending on the stimulus,
      IL-1ra accumulated linearly for periods up to 96 h. IL-1ra levels in synovial
      fluids of 19 patients suffering from various inflammatory joint diseases were
      compared with the cytokine levels of IL-1 beta, IL-6, IL-8, and TNF-alpha.
      Highest positive correlations were found with IL-8 and IL-1 beta. In normal blood
      donors IL-1ra serum levels were 150-800 pg/ml (Median: 387 pg/ml). Owing to its
      sensitivity and large measuring range the newly developed assays appear to be
      suitable for measuring IL-1ra in cell cultures as well as in biological fluids.

PMID- 8157987
TI  - A fast and sensitive colorimetric assay for IL-6 in hepatoma cells based on the
      production of a secreted form of alkaline phosphatase (SEAP).
AB  - Structure-function studies of cytokines require that simple, sensitive and
      reliable biological assays are available. A well known property of interleukin-6
      (IL-6) is that of being able to induce transcription from several liver-specific
      promoters in human hepatoma cells. However, the available assays of IL-6 in
      hepatoma cells, which are either based on the detection of increased expression
      of endogenous acute phase response genes or on the activation of reporter genes
      transfected under the control of IL-6 responsive promoters, are not very
      sensitive and are time consuming. We have established a new assay for IL-6 in
      hepatoma cells which is based on the transfection of an IL-6 inducible
      promoter/secreted alkaline phosphatase (SEAP) gene fusion and which measures the
      inducible production and release of SEAP in the culture medium. SEAP activity is
      measured with a simple colorimetric assay that requires no cell manipulation,
      thus allowing a large set of samples to be analysed simultaneously. The CRP/SEAP
      assay can be used in studies on the structure-function relationships of human IL
      6.

PMID- 8157986
TI  - Clinical application of responder cell frequency estimates with four years of
      follow up.
AB  - Limiting dilution cultures have been used to estimate the frequency of T cells
      which respond to antigen stimulation in vitro, but nothing is known of the
      reproducibility of this assay when applied to human blood. We developed a
      simplified form of limiting dilution culture in which blood mononuclear cells
      were diluted in round bottom 96-well plates and cultured for 10 days. The assay
      was used to estimate the frequency of blood mononuclear cells proliferating in
      response to varicella-zoster virus antigen. 250 subjects aged 25-87 years were
      studied: 95 of these subjects had annual measurements repeated over a 4 year
      period. The coefficients of variation for intra-assay replicates was 5%, and for
      inter-assay comparisons was 17.6% and 26% for tests at a 1 or 3 month interval
      respectively. For subjects studied at 1 year intervals the coefficient of
      variation was 42% with the total variability equally distributed between the
      variation between subjects and the variation within subjects. These data provide
      the first quantitative data to validate limiting dilution cultures for the long
      term in vitro measurement of human T cell responses.

PMID- 8157988
TI  - Tracking of murine spleen cells in vivo: detection of PKH26-labeled cells in the
      pancreas of non-obese diabetic (NOD) mice.
AB  - Flow cytometry was used to track the in vivo migration of PKH26-labeled donor
      spleen cells from diabetic NOD mice that were injected into non-diabetic
      recipient NOD mice. Flow cytometric analysis of recipient mouse tissues revealed
      that the donor cells were present in the peripheral blood, spleen and lymph nodes
      24 h following injection and could still be detected after 28 days. PKH26(+)
      cells were also detectable in the pancreas 7 days after injection. Phenotypic
      analysis of the PKH26(+) cells that migrated into these target organs and tissues
      showed that the major cell population detected was Thy1.2(+) T-lymphocytes,
      predominantly the Thy1.2(+)/L3T4(+) subpopulation, but Thy1.2(+)/Lyt2(+) cells as
      well as B220(+) cells (B lymphocytes) were also present.

PMID- 8157989
TI  - Preservation of protein phosphoryl groups in immunoprecipitation assays.
AB  - A phosphorylation-sensitive immunoprecipitation protocol is presented which
      ensures quantitative and qualitative recovery of phosphoantigens from different
      phosphatase environments. The protocol is based on the phosphatase-inactivating
      properties of a specific mixture of chemical compounds included in the
      "classical" immunoprecipitation buffers.

PMID- 8157991
TI  - Quantitation of platelet derived growth factor receptors on cells from human
      arterial segments.
AB  - The study of receptor expression in tissue containing multiple cell types
      presents a two-fold problem. Firstly, in situ studies are difficult to perform
      quantitatively and secondly, enzymatic disruption of the primary tissue results
      in the loss of cell surface receptors which may or may not be resynthesised. In
      vitro culture of cells following isolation may also alter receptor expression. To
      circumvent these problems, we have devised a reproducible non-enzymatic method
      for releasing endothelial and smooth muscle cells from human arterial segments
      and separating the mixture into constituent cell populations, in order to
      facilitate semi-quantitative receptor investigation by ELISA. The method involves
      the mechanical disruption of small artery segments and passage through
      progressively smaller sieves, resulting in a mixed population of single cells.
      Magnetic beads covalently attached to identifying lectins or antibodies are then
      used in a multistep procedure to give highly enriched cell populations. The
      dissociation/enrichment steps can be modified to select other cell types which
      may be present in the primary tissue, such as macrophages. We have used these
      preparations for locating and semi-quantitating PDGF and EGF receptors on the
      constituent cells of human umbilical artery preparations by ELISA using
      monoclonal receptor antibodies.

PMID- 8157990
TI  - Flow cytometric analysis of the stability of antibody production by human x human
      x mouse heterohybridoma subclones.
AB  - Flow cytometry has been utilized to evaluate the stability of antibody production
      by unstable subclones of a human x human x mouse heterohybridoma. Heterogeneity
      of cell-associated immunoglobulin heavy chain expression was demonstrated in
      different subclones and an increased frequency of cells containing low levels of
      heavy chain was found to correlate with low antibody productivity. However, the
      majority of cells were not completely devoid of heavy chains suggesting that the
      genetic information for the gamma chain was not lost. In contrast, the gene
      encoding the kappa light chain was shown to be absent from the subclones
      expressing low levels of heavy chain and these subclones also contained
      substantially reduced levels of heavy chain mRNA, suggesting that the production
      of this protein was controlled at the level of transcription or mRNA stability.
      In conclusion, the correlation of staining intensity as observed by flow
      cytometry antibody productivity makes flow cytometry a suitable technique for the
      rapid evaluation of heterohybridoma cell lines used for antibody production.

PMID- 8157992
TI  - Clinical evaluation of a modified ELISA, using photobiotinylated DNA, for the
      detection of anti-DNA antibodies.
AB  - The measurement of anti-dsDNA antibodies is important for the diagnosis and the
      follow-up of patients with systemic lupus erythematosus (SLE). For routine
      detection of anti-dsDNA, the Farr assay and the immunofluorescence technique
      (IFT) on Crithidia luciliae proved to be very useful. The anti-dsDNA ELISA is not
      used for routine purposes in our institute since it is flawed by false-positive
      results due to binding of negatively charged (immune) complexes to the employed
      precoat (protamine sulphate). Recently, a new anti-dsDNA ELISA has been described
      in which photobiotinylated dsDNA is coated to streptavidin coated plates. To
      investigate whether this modified ELISA is more specific than the classical anti
      dsDNA ELISA, we tested sera of patients with SLE (n = 51), myasthenia gravis (MG,
      n = 25), rheumatoid arthritis (RA, n = 25) and Sjogren's syndrome (SS, n = 23)
      and sera of healthy blood bank donors (BBD, n = 25). In both assays the sera of
      the SLE patients gave significantly higher values than the sera of healthy blood
      bank donors. In the classical ELISA, 84% of the sera from patients with RA and
      28% of sera of patients with MG were found positive. For the modified assay the
      figures were 8% and 24%, respectively. This modified ELISA was further studied
      and clinically evaluated by comparing it with the classical anti-DNA ELISA and
      two other anti-DNA assays (Farr assay and IFT), using 500 sera sent to our
      institute for routine anti-DNA determination and sera of an additional 75 healthy
      blood bank donors. Quantitatively, both ELISAs showed the same high degree of
      correlation with the IFT. The modified ELISA gave a better correlation with the
      Farr assay than the classical anti-DNA ELISA. From our data we conclude that the
      ELISA using photobiotinylated DNA is a more reliable assay than the classical
      anti-DNA ELISA.

PMID- 8157993
TI  - A rapid method for measuring apoptosis and dual-color immunofluorescence by
      single laser flow cytometry.
AB  - A sensitive method for quantification of cells undergoing apoptosis that permits
      the simultaneous measurement of dual-color cell surface immunofluorescence is
      presented. Unfixed cells are stained with 7-amino-actinomycin D (7-AAD) for
      discrimination of live from early apoptotic cells and from cells which have lost
      membrane integrity (late apoptotic or necrotic, dead cells). Owing to its
      spectral characteristics 7-AAD can be combined with fluorescein-isothiocyanate
      (FITC) and phycoerythrin (PE) cell surface staining. After staining, the samples
      can be treated with paraformaldehyde (PF) solution to eliminate the risk for
      exposure of laboratory personnel to biohazardous agents and to preserve the cells
      through fixation for later analysis on the flow cytometer. The value of the
      method is shown on the measurement of apoptosis in human thymocytes and in human
      peripheral blood mononuclear cells (PBMC) exposed to various inducers of active
      cell death. The method is validated by fluorescent activated cell sorting in
      combination with morphologic examination of the sorted cells. The technique we
      are presenting is particularly valuable in a clinical setting because it allows
      rapid multiparameter analysis of apoptosis in combination with cell surface
      phenotype on biohazardous samples with single laser instrumentation.

PMID- 8157994
TI  - An adhesion assay using minimal shear force to remove nonadherent cells.
AB  - A new 96-well microtiter plate based adhesion assay was developed to measure weak
      cell adhesion. This assay is distinct from other adhesion assays by the procedure
      in which the nonadherent cells are removed. In most conventional adhesion assays,
      nonadherent cells are removed by aspiration followed by repeated washes. However,
      the shear force generated by such washing also detaches weakly adherent cells. In
      the minimal shear force adhesion assay (MSFA) described here, the removal of
      nonadherent cells is carried out by applying a gentle shear force in a fluid
      environment. In this procedure, adherent cells are not subjected to harsh and
      variable washing forces and are not exposed to surface tension caused by the
      removal of washing fluid between successive washes. Using the lymphoid cell lines
      XC1.5/51 and MPC11, the number of adherent cells determined by this new adhesion
      assay is three times higher than the conventional adhesion assay. This MSFA assay
      is simple, consistent, and easy to perform. With modifications for applying a
      defined shear force, this assay can be adopted to compare cell adhesion strength
      to various substrata.

PMID- 8157995
TI  - Measurement of the dissociation rate constant of antigen/antibody complexes in
      solution by enzyme-linked immunosorbent assay.
AB  - A reliable, convenient ELISA based method has been developed for measuring the
      dissociation rate constants of antigen/antibody complexes in solution. Its
      rationale is as follows: a solution containing the preformed antigen/antibody
      complex is diluted well below the equilibrium dissociation constant to initiate
      the dissociation and, at various times after the dilution, the amount of
      dissociated antibody contained in an aliquot is determined by a classical ELISA,
      using a brief incubation of the solution in antigen coated wells. To test the
      validity of this method, the dissociation rate constants for several
      antigen/antibody complexes were compared with those obtained by classical
      fluorescence based methods. The good agreement between both sets of data
      validates the ELISA procedure. The present method offers several advantages. It
      uses only minute amounts of sample which need not be purified; it requires no
      radioactive or fluorescent labelling of the antibody or antigen, and it can, in
      principle, be applied to any type of complex between macromolecules if an ELISA
      test can be set up to detect quantitatively one of the macromolecules.

PMID- 8157996
TI  - A rapid and sensitive chemiluminescence dot-immunobinding assay for screening
      hybridoma supernatants.
AB  - The present report describes a simple and rapid dot-immunobinding assay combined
      with a chemiluminescence detection system for screening hybridoma supernatants
      for specific monoclonal antibodies (MAbs). Small rectangular nitrocellulose
      filters dotted with either crude mixtures of antigens, or with control samples,
      were placed in six well plates, incubated with hybridoma supernatants, then
      stained with peroxidase-conjugated anti-mouse IgG. The reaction was performed
      with a chemiluminescence detection system. We used this method to screen
      hybridoma supernatants for MAbs against a 354 amino acid polypeptide of hog
      cholera virus (HCV) gp33-gp55 protein expressed as a fusion protein. We also
      extended it for the screening of MAbs against foot-and-mouth disease virus
      (FMDV). The chemiluminescence dot-immunobinding assay (CDIA) was compared with
      neutralization (N) and immunofluorescence (IF) screening tests and some FMDV
      seroneutralizing MAbs were found to be either poorly reactive or undetected by
      the IF test. The advantage of the present method is that it detects in only one
      step all MAbs detected in the IF and/or N tests together with some MAbs not
      detected by either of these methods. The present method is at least 356 times
      more sensitive than the IF test.

PMID- 8157997
TI  - Modulation of systemic cytokine levels by implantation of alginate encapsulated
      cells.
AB  - The availability of cell lines that are transfected with IL-4, IL-5 and IFN-gamma
      cytokine genes permits the prolonged in vivo delivery of functional cytokines in
      relatively large doses for the modulation of specific immune responses. Often the
      transfected cells are xenogeneic or allogeneic to the experimental animal and
      have to be encapsulated in such a way that no cellular response by the host will
      be induced. Alginate has proven to be a simple matrix for encapsulating cells
      under mild conditions suitable for in vivo implantation. Encapsulated cells
      express the transfected IL-4 gene for at least 14 days after in vivo implantation
      and were shown to be functional during that period by modulating ongoing IgE
      responses. The application of adherent growing transfected cells permits dose
      response titrations and provides an easy method for local and systemic cytokine
      delivery. Alternatively, hybridoma cells can be encapsulated and the secreted
      antibody monitored in the serum. It was found that no host immune response was
      triggered by alginate encapsulated cells. The efficiency of treatment by
      encapsulated hybridoma cells was shown to be equivalent to that of injecting
      purified antibodies.

PMID- 8157998
TI  - Binding units (BU) and the area under binding isotherms (AUI). New indices of
      effector-target conjugation.
AB  - New methods for simplified quantitation of effector-target conjugation have been
      developed. The binding unit (BU) is defined as the number of target cells
      required to bind a specified percentage of effector cells. The number of binding
      units is determined from binding isotherms in which effector conjugate
      frequencies are measured by holding constant the number of effector cells and by
      varying the number of target cells. Alternately, a binding unit can be defined as
      the number of effector cells required to bind a specified percentage of target
      cells. In this case, BU is computed from binding isotherms in which target
      conjugate frequencies are measured at different values of effector cells by
      holding constant the number of target cells. Also, the area under the curve (AUI)
      of these isotherms is another index that can be used as an overall measure of the
      binding capacity in an effector-target system. The experimental values of BU and
      AUI determined from effector and target isotherms agree well with theoretical
      predictions based on our previously developed binding model (J. Immunol. Methods
      (1992) 155, 133-147). The relationship between BU and AUI, and procedures to
      determine these parameters are shown. The value of these indices to express
      effector-target conjugation quantitatively has been confirmed by determining the
      values of BU and AUI for the NK-K562 effector-target system.

PMID- 8157999
TI  - A new rapid and simple non-radioactive assay to monitor and determine the
      proliferation of lymphocytes: an alternative to [3H]thymidine incorporation
      assay.
AB  - A one-step non-radioactive assay to determine the proliferation of murine
      lymphocytes, lymphoid tumor cells and hybridoma cells is described. This assay
      requires the addition of Alamar Blue dye to cell cultures and the degree of
      change in its color, which is reflective of the extent of cellular proliferation,
      can be determined by an ELISA plate reader. Alamar Blue must be added during the
      initial phase of cell culture. The pattern of concanavalin A (ConA) or anti-CD3
      antibody-induced proliferative response of murine lymphocytes as assessed by
      Alamar Blue was similar to that of a [3H]thymidine assay. Similarly, the
      spontaneous proliferation curve of anti-CD3 antibody secreting cell line (YCD3
      1), monocytic macrophage cell lines (PU5-1.8, P388D1, J774.1) and myeloma cells
      (Sp2/0) as determined by Alamar Blue closely resembled that of the [3H]thymidine
      assay. The minimum detectable number of proliferating cells was comparable in
      Alamar Blue and [3H]thymidine assays. Since cell lysis/extraction and washing
      procedures are not involved in the Alamar Blue assay, this approach has several
      distinct advantages over currently available assays (eg. [3H]thymidine). First,
      it allows daily monitoring of proliferation without compromising the sterility of
      cultures. An indication of proliferation can be evaluated (spectrophotometrically
      or visually) as early as 24 h after ConA stimulation. Second, unlike previously
      reported assays, Alamar Blue permits further analysis of proliferating cells by
      other methods. Analysis of cells in culture with Alamar Blue for various surface
      antigens (CD44, CD45RB, CD4, heat stable antigen) by flow cytometry revealed that
      the fluorescent profile and relative percentage of cells in cultures with the
      Alamar Blue were comparable to those without this reagent. The salient advantages
      of Alamar Blue assay over the [3H]thymidine assay include: (i) non-radioactivity;
      (ii) simplicity; (iii) less costly; (iv) non-labor intensive; (v) rapidity of
      assessment of proliferation of large number of samples; (vi) non-toxicity; (vii)
      usefulness in determining the kinetics of cell growth of hybridomas; and (viii)
      non-interference of secretion of antibodies by a hybridoma cell line.

PMID- 8158000
TI  - Liposome immunoassay (LIA) for gentamicin using phospholipase C.
AB  - A simple and sensitive liposome immunoassay for gentamicin was developed using
      the cytolytic agent, phospholipase C, instead of complement. Liposomes entrapping
      a fluorescent marker, calcein, were prepared by the reverse-phase evaporation
      method from a mixture of dimyristoylphosphatidylcholine and cholesterol (molar
      ratio of 3:1). Gentamicin, a model analyte, was covalently coupled to
      phospholipase C by 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide and N
      hydroxysuccinimide. Liposomes were lysed by gentamicin-phospholipase C conjugate
      and an entrapped fluorescent marker was released. The lytic activity of
      gentamicin-phospholipase C conjugate was inhibited in the presence of gentamicin
      antiserum. The standard calibration curve was constructed by plotting percentage
      of liposome lysis versus log concentration of free gentamicin. The standard
      calibration curve was linear over 2.5 pg/ml approximately 2.5 ng/ml of gentamicin
      concentrations. This newly developed immunoassay is simple, relatively rapid and
      potentially applicable to the determination of concentration of antigens, drugs
      and endogenous substances.

PMID- 8158001
TI  - Characterization of monoclonal antibodies specific for monocytes, macrophages and
      granulocytes from porcine peripheral blood and mucosal tissues.
AB  - A panel of four monoclonal antibodies produced in our laboratory, MIL1, MIL2,
      MIL3, MIL4, and the type-specific monocyte/granulocyte marker 74-22-15 were used
      to isolate and to discriminate between monocytes, macrophages and granulocytes
      derived from porcine peripheral blood, lung and gut lamina propria. Two-colour
      flow cytometry and cell sorting showed that while no monoclonal antibody was
      specific for just a single cell population, each cell type had a unique and
      characteristic combination of surface antigens. These differences could be used
      to identify and purify monocytes, macrophages, neutrophils, eosinophils and
      basophils from the three different sites. The study also demonstrated
      similarities and differences within cell types from the same site and from
      different sites: polymorphonuclear neutrophils (PMN) from peripheral blood were
      subdivided into two subpopulations by the presence or absence of the surface
      antigen recognized by MIL4, while PMN from alveolar lavage did not express this
      antigen. Peripheral blood eosinophils were also divided into subpopulations by
      the presence or absence of the same surface antigen. Lamina propria eosinophils
      strongly expressed the MIL4 marker and differed morphologically from blood
      eosinophils. Peripheral blood basophils and lamina propria mast cells were
      morphologically similar and expressed similar antigens. Monocytes and alveolar
      macrophages also expressed the same surface antigens.

PMID- 8158002
TI  - Distinction of highly homologous pregnancy-specific glycoprotein (PSG) isoforms
      by differential absorption of antisera with recombinant PSG fusion protein
      domains.
AB  - The N-terminal domains of two different highly homologous isoforms of pregnancy
      specific beta 1 glycoproteins (PSGs) were expressed in bacteria. The N-terminal
      domain of PSG1 (PSG1-N) and PSG3 (PSG3-N) were chosen since PSG3-N, but not PSG1
      N, contains an RGD sequence. Immunosorbents were prepared using bacterially
      expressed fusion proteins with the respective N domains. Antibodies from a
      polyclonal antiserum against native PSG were eluted from PSG1-N and were
      subsequently absorbed against PSG3-N. Using this procedure, antibodies were
      generated that were able to bind to native PSG and PSG1-N, but not to PSG3-N.
      These results show that the antiserum against native PSG crossreacts with PSG
      isoforms of two subgroups. From the PSG antiserum, antibodies can be isolated
      that differentially bind to V-like PSG domains which differ by eight non
      conservative amino acid substitutions, three of which are clustered in a position
      corresponding to the CDR III of immunoglobulin V region domains. Purification of
      antibody populations by this technique should make it possible to distinguish
      rapidly between highly homologous PSG isoforms in tissues and body fluids.

PMID- 8158003
TI  - Efficient transfer of antibodies into mammalian cells by electroporation.
AB  - An optimized protocol for electroporation is described which is suitable for
      introducing antibodies into mammalian cells. The method results in the uptake of
      detectable amounts of antibodies in 80% of the cells and in 40% large amounts are
      introduced. As an example, cell cycle activity (transition from the G1 to S
      phase) was inhibited by the introduction of monoclonal antibodies against G1
      specific cyclin D1 into CV-1 and MCF7 cells. This specific antibody mediated
      inhibition of cellular function did not affect the viability of the cells since
      they recovered from the inhibition after some time. While approaching the
      efficiency of microinjection, the new protocol for electroporation of antibodies
      additionally permits treatment of the larger number of cells which are required
      for biochemical analyses.

PMID- 8158004
TI  - Evaluation of the MTT and SRB assays for testing LAK cell-mediated growth
      inhibition of various adherent and non-adherent tumor target cells.

PMID- 8158005
TI  - Role of IMA in prevention and control of AIDS.

PMID- 8158006
TI  - National AIDS control programme and generation of awareness in medical
      profession.

PMID- 8158007
TI  - AIDS and society.

PMID- 8158008
TI  - HIV/AIDS epidemic in Asia: the current situation and strategies for prevention.

PMID- 8158009
TI  - AIDS--glimpses of African experience.

PMID- 8158010
TI  - The importance of counselling in the care of persons with HIV infection or AIDS.

PMID- 8158011
TI  - Ethical and legal issues and AIDS.

PMID- 8158012
TI  - Acquired immunodeficiency syndrome and some social problems.

PMID- 8158013
TI  - HIV testing policy and surveillance.

PMID- 8158014
TI  - AIDS: a paediatric perspective.

PMID- 8158015
TI  - Infection control in the health care settings.

PMID- 8158016
TI  - AIDS today.

PMID- 8158017
TI  - AIDS: perspective and strategy.

PMID- 8158019
TI  - AIDS problems.

PMID- 8158018
TI  - Tuberculosis and HIV infection.

PMID- 8158020
TI  - BK and JC viruses in human immunodeficiency virus type 1-infected persons:
      prevalence, excretion, viremia, and viral regulatory regions.
AB  - Human polyomavirus BK (BKV) and JC (JCV) infections were examined in persons
      infected with human immunodeficiency virus type 1 (HIV-1). High frequencies of
      BKV (24%) and JCV viruria (16%) were detected by polymerase chain reaction (PCR).
      BKV viruria was not found in an immunocompetent control group, in contrast to a
      frequency of JCV viruria of 20%. The degree of HIV-induced immunodeficiency did
      not influence the prevalence of BKV viruria, in contrast to cytomegalovirus
      viruria, suggesting BKV reactivation is an early manifestation in HIV infection
      as well as a temporal sequence of opportunistic infections. BKV DNA but not JCV
      DNA was detected in peripheral blood mononuclear cells (PBMC) in 2 of 42 subjects
      by a sensitive nested PCR. Sequencing of viral noncoding control regions (NCCRs)
      revealed predominantly archetypal and TU type BKV NCCRs but only archetypal JCV
      NCCRs. A new, naturally occurring BKV NCCR variant was detected in 1 urine
      specimen and 2 PBMC samples, indicating a stable and biologically significant
      rearrangement. Serum levels of BKV antibodies do not seem to be diagnostically
      useful in HIV-infected persons.

PMID- 8158021
TI  - Differential immune responsiveness to the immunodominant epitopes of regulatory
      proteins (tax and rex) in human T cell lymphotropic virus type I-associated
      myelopathy.
AB  - Infection by human T cell lymphotropic virus type I (HTLV-I) is etiologically
      linked with HTLV-I-associated myelopathy (HAM) or adult T cell leukemia (ATL). To
      evaluate the contribution of the viral regulatory proteins tax and rex during the
      development of disease, antibody responses to these proteins were analyzed in
      patients with HAM (n = 28) or ATL (n = 48) and in asymptomatic carriers (n = 69).
      Epitope mapping analysis identified immunodominant epitopes towards the amino
      terminus (Tax8(106-125)) and at the carboxyl terminus (Tax22(316-335), Tax23(331
      350), and Tax24(336-353)) of tax and the amino terminus (Rex1(1-20), Rex2(16-35),
      Rex4(46-65), and Rex6(76-95)) of rex. Analysis of antibody reactivity to these
      immunodominant epitopes demonstrated preferential reactivity to Tax8, Tax22,
      Tax23, and Tax24 (71%-93%) and to Rex4 and Rex6 (52%) in patients with HAM when
      compared with reactivities in ATL patients (4%-31% for tax and 19%-24% for rex)
      or asymptomatic carriers (27%-37% for tax and 7%-23% for rex). In contrast,
      antibody responses to the immunodominant epitopes of the env proteins of HTLV-I
      (MTA, Env1, Env5) were similar in all of three clinical groups. Thus,
      differential immune responsiveness to the immunodominant epitopes of tax and rex
      in patients with HAM may play a role in disease pathogenesis in HTLV-I-infected
      persons.

PMID- 8158022
TI  - Anti-rotavirus G type-specific and isotype-specific antibodies in children with
      natural rotavirus infections.
AB  - Serum VP7 (G) type- and isotype-specific anti-rotavirus antibodies were assessed
      among children monitored longitudinally over one or two rotavirus seasons in day
      care centers. Seventy-five pairs of blood specimens from 63 children were tested
      for anti-rotavirus antibodies. Stool specimens were collected weekly and tested
      for rotavirus antigen. G typing of detected rotaviruses showed that seven
      outbreaks of G1 and one of G3 occurred during the two seasons. G type-specific
      responses to the outbreak strain occurred among 79% of infected children and 9%
      of children with infection not detected (P < .001). Of children infected with G1,
      54% had a heterotypic response; they were older (P = .048) and had higher
      preexisting G1 antibody levels than children who had only homotypic responses (P
      = .012). Higher IgA, IgG, and homotypic antibody levels to the antigenic site C
      of the G1 and G3 VP7s correlated with protection against infection and illness,
      homotypic antibody independently of IgA or IgG titers.

PMID- 8158023
TI  - Endemic nosocomial transmission of Staphylococcus epidermidis bacteremia isolates
      in a neonatal intensive care unit over 10 years.
AB  - To assess long-term nosocomial transmission, trends in antibiotic resistance, and
      expression of potential virulence factors, 86 randomly selected Staphylococcus
      epidermidis bloodstream isolates obtained from 80 patients in a neonatal
      intensive care unit (NICU) over a 10-year period were studied. Pulsed-field gel
      electrophoresis (PFGE) analysis of SmaI-digested whole chromosomal DNA revealed
      distinctive banding patterns that persisted in the NICU over long periods.
      Pattern A included 22 isolates (26%) obtained during 1983-1990, and pattern B
      included 24 isolates (28%) from 1983 to 1991. All 10 isolates examined in 1984
      fell into one of these two patterns. Isolates with either pattern expressed
      polysaccharide/adhesin (PSA) and slime; 90% and 87% were resistant to oxacillin
      and gentamicin, respectively, with no trends over time. These findings suggest
      that distinct clones of S. epidermidis can become endemic in NICUs over periods
      as long as a decade and that nosocomial transmission plays an important role in
      neonatal S. epidermidis bacteremia.

PMID- 8158024
TI  - Human experimentation with Neisseria gonorrhoeae: rationale, methods, and
      implications for the biology of infection and vaccine development.
AB  - Neisseria gonorrhoeae infection is limited to the human host. Experimental
      urethral infection in male volunteers was used to study different aspects of the
      infection. Urethral installation of a variety of gonococcal variants (10(4)
      10(6)) led to infection in 27 subjects, who developed pyuria and shed bacteria in
      urine before urethritis developed 1-6 days after gonococcal inoculation. The
      incubation period was affected by the inoculation procedure and size of the
      inoculum. Subjects were treated with intramuscular ceftriaxone (250 mg) if
      urethritis developed or at 6 days after inoculation. Urine cultures became
      negative within several hours of therapy, and symptoms resolved within 1 day of
      therapy. Infected patients suffered no major complications. Experimental male
      urethral gonococcal infection provides a unique opportunity to understand the
      biology and immunology of gonococcal infection and is an efficient method to test
      gonococcal vaccine candidates.

PMID- 8158025
TI  - Pathogenesis of Shigella diarrhea: XVII. A mammalian cell membrane glycolipid,
      Gb3, is required but not sufficient to confer sensitivity to Shiga toxin.
AB  - Shiga toxin recognizes a galactose-alpha 1-->4-galactose terminal glycolipid,
      globotriaosylceramide (Gb3), in sensitive mammalian cells and is translocated by
      endocytosis to the cytoplasm, where it blocks protein synthesis. To determine if
      Gb3 is both required and sufficient for toxicity, Gb3 content in cells was
      altered by blocking key biosynthetic or degradative path enzymes with specific
      inhibitors. The resulting decrease or increase in cellular Gb3 was associated
      with a decrease or increase in binding of and response to Shiga toxin. Toxin
      resistant Gb3-deficient variants of sensitive cells fused with liposomes
      containing Gb3 but not globotetraosylceramide (Gb4) became susceptible, whereas
      fusion of Gb3 liposomes to naturally resistant Gb3-deficient CHO cells increased
      toxin binding but not cytotoxicity. These data demonstrate that Gb3 is required,
      but not sufficient, for the action of Shiga toxin and suggest the existence of a
      toxin translocation mechanism linked to surface glycolipids that is not expressed
      in CHO cells.

PMID- 8158026
TI  - Outbreaks of Salmonella enteritidis infections in the United States, 1985-1991.
AB  - The spread of Salmonella enteritidis infections in the United States was tracked
      to identify potential risk factors and preventive measures. Isolation rates and
      information regarding outbreaks of S. enteritidis from 1985 through 1991 were
      determined by reports to the national Salmonella surveillance system and through
      the foodborne disease outbreak surveillance system. From 1985 through 1991, 380
      outbreaks were reported involving 13,056 ill persons and 50 deaths. The
      proportion of Northeast outbreaks fell from 81% in 1985 to 55% in 1991 as the
      number of outbreaks in other areas increased. Grade A shell eggs were implicated
      in 82% of outbreaks. Case-fatality rates in nursing homes and hospitals were 70
      times higher than in other settings. Cultures of environmental or animal
      specimens from all farms tested yielded S. enteritidis. Eggborne S. enteritidis
      infections are a major public health problem. Preventive measures, including
      educating consumers about proper handling of eggs, using pasteurized eggs, and
      controlling infections on egg farms, may stem the impact of this disease.

PMID- 8158027
TI  - Desferrioxamine-promoted virulence of Yersinia enterocolitica in mice depends on
      both desferrioxamine type and mouse strain.
AB  - The effects of desferrioxamine B (DFOB) and G (DFOG) on growth promotion and
      virulence of Yersinia enterocolitica as well as on T cell activation and
      proliferation were investigated. Both desferrioxamines promoted growth of Y.
      enterocolitica O:8 (WA-314) and O:3 (Y-108). DFOB had a greater immunosuppressive
      effect on T cells than did DFOG. These results suggest a dual role of DFOB in
      yersiniosis: growth promotion of the pathogen and immunosuppression of the host.
      The LD50 of both Yersinia strains for mice was reduced by DFOB but not by DFOG.
      However, the LD50 of yersiniae was reduced by DFOB to a greater extent in
      Yersinia-resistant C57BL/6 than in Yersinia-susceptible BALB/c mice. The
      different impact of DFOB on the LD50 of Y. enterocolitica in C57BL/6 and BALB/c
      mice might be due to an immunomodulating effect of DFOB.

PMID- 8158029
TI  - Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects
      of antibiotics against Mycobacterium avium complex infection in the beige mouse
      model.
AB  - Previous studies have shown that recombinant granulocyte-macrophage colony
      stimulating factor (GM-CSF) stimulates human and murine macrophages to inhibit
      growth and kill intracellularly. This study shows the effect of GM-CSF on
      Mycobacterium avium complex (MAC) infection in vivo using a C57BL/6 beige mouse
      model of disseminated MAC infection. Furthermore, it examined the activity of the
      combination of GM-CSF and amikacin or azithromycin, two antimicrobials active
      against MAC, on the survival of MAC within macrophages in vitro and in the mouse
      model of disseminated infection. Although GM-CSF (25 mg/kg) induced
      mycobactericidal and mycobacteriostatic activity in macrophages in vitro and in
      vivo, the combination of GM-CSF and amikacin (50 mg/kg) or azithromycin (250
      mg/kg) was associated with a significant increase in killing of MAC both within
      cultured macrophages and in the beige mouse model. Therefore, a significant
      reduction in the number of viable bacteria was observed in blood, liver, and
      spleen of mice treated with a combination of GM-CSF and azithromycin or amikacin
      compared with control mice and those treated with GM-CSF or antimicrobials alone.

PMID- 8158028
TI  - Sera from patients with chronic Lyme disease protect mice from Lyme borreliosis.
AB  - Sera from selected patients with Lyme disease in different stages were used to
      passively immunize mice against Borrelia burgdorferi challenge to determine if
      human antibodies could protect the animals from infection. Sera from 2 patients
      with late-stage Lyme disease that contained strong antibody reactivity to
      proteins in B. burgdorferi lysates, including antibodies to the outer surface
      proteins (Osps) A and B, partly protected mice from infection after challenge
      with a small inoculum (10(2)) of B. burgdorferi. Mice immunized with sera from
      either of these 2 patients developed significantly fewer infections from the
      borreliae (patient 1 serum, 5%; patient 2 serum, 25%) relative to control mice
      (patient 1 serum, 90%; patient 2 serum, 74%). In contrast, sera from 2 patients
      with early or late Lyme disease that lacked antibodies reactive to OspA and OspB
      did not confer protection. Immunity appeared to be related, at least in part, to
      the presence of a strong humoral response to the Osps. These results suggest that
      during prolonged infection, some patients develop an immune response that may be
      partly protective against reinfection with B. burgdorferi. Therefore, although
      most patients do not mount a strong humoral response to the Osps during natural
      infection, vaccination with an Osp may elicit protective immunity.

PMID- 8158030
TI  - The etiology of early childhood diarrhea: a community study from Guinea-Bissau.
AB  - A potential enteropathogen was found in 50% of 1219 diarrheal episodes and 48% of
      511 asymptomatic controls in a 1-year community study of childhood diarrhea.
      Rotavirus (3% of episodes), Cryptosporidium species (6%), and enteropathogenic
      Escherichia coli (EPEC) with EPEC adherence factor (4%) were more prevalent in
      cases than controls. Giardia lamblia (19%) was the most prevalent organism but
      was not associated with diarrhea. Enterotoxigenic E. coli (12%), Strongyloides
      stercoralis (5%), Shigella species (2%), Entamoeba histolytica trophozoites (2%),
      and Vibrio cholerae (1%) were found at nonsignificantly higher rates. Salmonella
      and Campylobacter species were more prevalent among control infants.
      Cryptosporidium species and sequential infections from other pathogens caused
      persistent diarrhea.

PMID- 8158031
TI  - Immunity to onchocerciasis: identification of a putatively immune population in a
      hyperendemic area of Ecuador.
AB  - The existence of immunity to Onchocerca volvulus (Ov) infection is suggested by
      the presence of uninfected persons in hyperendemic areas. A major barrier to the
      study of immunity has been the correct identification of putatively immune (PI)
      subjects. To identify a PI group in a hyperendemic area in Ecuador, clinical and
      epidemiologic information was combined with a polymerase chain reaction (PCR)
      based assay identifying Ov DNA in skin snips and a recombinant antigen-based
      ELISA. Comparison of immune responses revealed that PI subjects had significantly
      lower levels of Ov-specific IgG, IgG subclasses, and IgE than infected (INF)
      subjects. Female subjects were significantly more likely to be PI than male
      subjects, and INF female subjects had significantly lower levels of Ov-specific
      IgG, IgG1, and IgG3 than INF male subjects. Thus, the use of molecular-based
      techniques has helped to define more precisely the PI state in onchocerciasis.

PMID- 8158033
TI  - Effectiveness of diethylcarbamazine in treating loiasis acquired by expatriate
      visitors to endemic regions: long-term follow-up.
AB  - Although successful treatment of loiasis with diethylcarbamazine (DEC) has been
      reported, little is known about the long-term success rate of therapy or the
      predisposing factors for treatment failure. To address these questions, 32
      patients were followed 2-15 years (median, 4.5) after DEC treatment; all had
      acquired infection while expatriate visitors to endemic areas of Africa. Using a
      strict definition of successful treatment, 12 (38%) appeared to be cured after
      one course of therapy and 5(16%) after two courses. Of the remaining 15 patients,
      3 continued to be symptomatic despite more than four courses of treatment.
      Although 12 of the 17 patients who relapsed did so within 1 year of treatment,
      several had relatively long asymptomatic periods (2-8 years). There was no
      predictive difference in clinical or laboratory parameters (including
      eosinophilia and specific filarial serology) between patients requiring one or
      more courses of therapy.

PMID- 8158032
TI  - Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo
      controlled study.
AB  - A double-blind, placebo-controlled study of mefloquine antimalarial prophylaxis
      in pregnancy (> 20 weeks of gestation) was conducted in 339 Karen women living in
      an area of multidrug-resistant malaria transmission on the Thai-Burmese border.
      Mefloquine gave > or = 86% (95% confidence interval [CI], 59%-94%) protection
      against Plasmodium falciparum and complete protection against Plasmodium vivax
      infections. Mefloquine prophylaxis was well tolerated; use of an initial loading
      dose (10 mg/kg) was associated with transient dizziness, but there were no other
      significant adverse effects on the mother, the pregnancy, or infant survival or
      development (followed for 2 years). Falciparum malaria was associated with
      maternal anemia and a mean reduction in birth weight in gravidae I, II, and III
      of 225 g (95% CI, 26-423). Maternal anemia at delivery (hematocrit < 30%) was
      associated with increased infant mortality: 26% versus 15% (relative risk, 1.9;
      95% CI, 1.1-3.2). Mefloquine is safe and effective for antimalarial prophylaxis
      in the second half of pregnancy.

PMID- 8158034
TI  - Apparent selection against transmission of zidovudine-resistant human
      immunodeficiency virus type 1 variants.
AB  - The sexual transmission of zidovudine-resistant human immunodeficiency virus type
      1 (HIV-1) variants was investigated in 5 donor-recipient pairs in which all
      donors and none of the recipients had received zidovudine treatment. The virus
      isolates were tested for sensitivity to zidovudine (IC50) in vitro using blood
      donor lymphocytes. A region of the HIV-1 pol gene was also directly sequenced by
      a solid-phase sequencing method. Four donors were shown to have zidovudine
      resistant HIV-1 variants. Two of these patients had a single mutation (Thr215-
      >Tyr), and 2 had a double mutation (Met41-->Leu and Thr215-->Tyr) that previously
      has been shown to confer zidovudine resistance. Zidovudine-resistant virus was
      found in only 1 of the 4 recipients, which indicates that zidovudine-resistant
      HIV-1 variants may be selected against during transmission. Thus, the
      transmission of zidovudine-resistant HIV-1 variants is a complex process that
      will require consideration whenever zidovudine treatment is initiated in persons
      who may have been infected by resistant variants.

PMID- 8158035
TI  - Intestinal secretory IgA immune response against human immunodeficiency virus
      among infected patients with acute and chronic diarrhea.
AB  - Diarrhea is common in patients infected with the human immunodeficiency virus
      (HIV) in Africa. There has been speculation that HIV itself may cause some of the
      enteropathy seen. The intestinal secretory IgA (sIgA) response was used to
      evaluate HIV intestinal infections in Zambian patients with acute and chronic
      diarrhea. sIgA was extracted from stool specimens and evaluated by an ELISA.
      Seven (58%) of 12 HIV-positive patients with acute diarrhea and 25 (69%) of 36
      HIV-positive patients with chronic diarrhea showed an sIgA response to HIV p24,
      compared with 1 of 10 HIV-positive patients without diarrhea (P < .025 for acute
      and P < .001 for chronic diarrhea). The mean duration of diarrhea was
      significantly longer in patients showing an anti-p24 response. An sIgA response
      to HIV antigens occurs commonly in infected patients with diarrhea and may
      provide further evidence of an etiologic role of HIV in the diarrhea associated
      with AIDS.

PMID- 8158036
TI  - Opportunistic events and p17 expression in the bone marrow of human
      immunodeficiency virus-infected patients.
AB  - Bone marrow biopsies from 114 human immunodeficiency virus (HIV)-infected
      patients were stained with an anti-p17 monoclonal antibody to detect active HIV
      replication and associated factors. Immunoreactive p17 was found as virus-like
      particles in macrophages and dendritic cells and occasionally in megakaryocytes
      in 62 of 114 marrows and was considered evidence of active HIV replication.
      Immunoreactive p17 was not found significantly more often in the marrows of
      patients with lower CD4 cell counts; however, it was found significantly more in
      the marrows of patients with concurrent mycobacterial or fungal infections or
      lymphoma (chi 2 = 12.1, P < .001). Immunoreactive p17 was even more frequent when
      these opportunistic diseases were found in the biopsied marrow (chi 2 = 20.5, P <
      .001). The association of active HIV replication with certain opportunistic
      diseases, but not with lower CD4 cell counts, raises the possibility that these
      opportunistic diseases may under some circumstances be a cause as well as a
      consequence of active HIV replication.

PMID- 8158037
TI  - Immunoglobulin prophylaxis against human T cell lymphotropic virus type II in
      rabbits.
AB  - Hyperimmune globulins, I-IgG and II-IgG, prepared from healthy persons
      seropositive for human T cell lymphotropic virus (HTLV) types I and II,
      respectively, were tested for their prophylactic effect against HTLV-II infection
      in rabbits. Three groups (A, B, and C) of 3 female rabbits each were used. Group
      A rabbits were inoculated intravenously with HTLV-II-carrying rabbit lymphoid
      cell line RII. Group B and C rabbits were immunized, respectively, with II-IgG
      and I-IgG and challenged with RII cells 24 h later. All group A and C rabbits
      seroconverted for HTLV-II after 2 weeks, but all group B rabbits were protected
      from HTLV-II infection. Gene amplification by polymerase chain reaction revealed
      the presence of HTLV-II provirus sequences in all group A and C rabbits but in
      none of the group B rabbits. These findings indicate that passive immunization
      with II-IgG is effective in preventing HTLV-II infection and that there is no
      cross-neutralization between HTLV-I and -II.

PMID- 8158038
TI  - Detection of cytomegalovirus in cerebrospinal fluid autopsy specimens from AIDS
      patients.
AB  - Cytomegalovirus (CMV) is a common opportunistic pathogen infecting AIDS patients.
      Polymerase chain reaction (PCR) and antigen capture ELISA were used to detect CMV
      in 40 cerebrospinal fluid autopsy specimens from patients with AIDS. CMV DNA was
      detected by PCR in 70% of samples. Of the 21 samples from patients with systemic
      CMV infection, 57% had CMV encephalitis, while 81% had virus in cerebrospinal
      fluid detectable by PCR. Of the 24 samples from patients with no histologic
      evidence of CMV encephalitis, 58% had CMV DNA in cerebrospinal fluid detected by
      PCR. These results suggest that PCR of cerebrospinal fluid sensitively detects
      systemic CMV infection but is not specific for brain infection in autopsy
      specimens of AIDS patients.

PMID- 8158039
TI  - Hepatitis B virus activation among central Africans infected with human
      immunodeficiency virus (HIV) type 1: pre-s2 antigen is predominantly expressed in
      HIV infection.
AB  - To evaluate the impact of human immunodeficiency virus (HIV) type 1 on the
      natural history of hepatitis B virus (HBV) infection, sera from Central Africans
      with and without antibodies to HIV were examined for HBV markers of ongoing
      replication, recovery from infection, and reactivation or reinfection. The
      prevalence of HBV infection and HBV surface antigen (HBsAg) was similar for HIV
      positive and -negative persons. AIDS patients were more likely to be HBsAg
      positive and have markers of viral replication. Unlike pre-surface (pre-s) 1
      antigen (Ag), which did not differ significantly with respect to HIV infection,
      pre-s2Ag was more common among HIV-positive persons than among HIV-negative ones
      and was more common among AIDS patients than among HIV-positive asymptomatic
      carriers. HIV-positive persons had more markers consistent with HBV reactivation
      and lower levels of antibody to HBsAg.

PMID- 8158040
TI  - Possible role of high-titer maternal viremia in perinatal transmission of
      hepatitis C virus.
AB  - To study perinatal transmission of hepatitis C virus (HCV), 15 anti-HCV-positive
      carrier mothers without human immunodeficiency virus coinfection were recruited.
      At delivery, maternal blood was taken and anti-HCV titer was determined and HCV
      RNA measured in each serum sample by reverse transcription polymerase chain
      reaction (PCR). A competitive PCR was used in selected samples to quantitate HCV
      concentration. The 15 neonates were followed regularly for 1 year and their sera
      were also assayed for anti-HCV and for HCV RNA by reverse transcription PCR. All
      the mothers were positive for HCV RNA. Only one normal spontaneously delivered
      neonate of a mother with extremely high titer of anti-HCV (1:20,000) and HCV
      concentration (10(10) copies/mL) had both anti-HCV and HCV RNA in serum for up to
      6 months of age. In contrast, none of the remaining 14 neonates born to mothers
      with low- to high-titer anti-HCV (1:4-1:1000) and moderate amounts of HCV RNA
      (10(5)-10(6) copies/mL) contracted HCV infection. The results imply that high
      titer maternal viremia and normal spontaneous delivery may allow more HCV to
      infect the neonate intrapartum, therefore establishing perinatal transmission.

PMID- 8158041
TI  - Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine.
AB  - (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), a high-potency
      antiherpes and anticytomegalovirus (CMV) drug was evaluated in the treatment of
      experimental retinitis caused by preretinal herpes simplex virus (HSV-1)
      injection in rabbits. HPMPC (100 micrograms/0.1 mL) was intravitreally injected
      10, 15, 21, 30, or 46 days before, concurrently, or 3, 5, or 7 days after viral
      inoculation. Ganciclovir (200 micrograms/0.1 mL) was intravitreally injected 3,
      7, or 10 days before HSV-1 inoculation, concurrent with viral inoculation, or 3,
      5, or 7 days after viral inoculation. Eyes pretreated with HPMPC were protected
      from retinitis for 15-21 days. Ganciclovir did not protect completely even if
      administered 3 days before inoculation. Early treatment of established retinitis
      with HPMPC markedly delayed the progression of the infection. However, with
      ganciclovir there was delayed progression only in rabbits treated 3 days after
      viral inoculation. HPMPC had a remarkably potent and prolonged (< or = 1 month)
      antiviral effect in this retinitis model and may prove more useful than
      ganciclovir in local treatment of CMV retinitis.

PMID- 8158042
TI  - Passive immunization of the vagina protects mice against vaginal transmission of
      genital herpes infections.
AB  - Vaginal application of human herpes simplex virus (HSV) antiserum, complement
      inactivated antiserum, or IgG purified from antiserum protected mice (P < .001, P
      < .001, and P < .01, respectively) from visible signs of genital HSV-2 infection
      after subsequent vaginal inoculation with HSV-2 (10 ID50). Vaginal application of
      an anti-HSV-2 monoclonal antibody (MAb III-174) also protected mice against
      infection. This MAb, a neutralizing mouse IgG2A against glycoprotein D, prevented
      infection as determined by viral shedding from the vagina (P < .05), blocked 50%
      of visible signs of genital herpes infection at a vaginal dose of approximately
      10 ng, and blocked 100% of visible signs of infection at a vaginal dose of 1
      microgram (P < .001). These results suggest that vaginal applications of anti-HSV
      antibodies may help prevent sexual transmission of genital herpes infection.

PMID- 8158043
TI  - Varicella-zoster virus (VZV) reactivation is related to the low response of VZV
      specific immunity after chickenpox in infancy.
AB  - To clarify the cause of herpes zoster in immunocompetent children, specific
      humoral and cellular immunity was determined using an ELISA and a
      lymphoproliferative assay, respectively, in infants < 1 year of age and children
      > or = 1 year of age who had chickenpox. Thirteen (59.1%) of 22 infants, 17
      (81.0%) of 21 children > or = 1 year of age (P < .02), and 13 (86.7%) of 15
      children > or = 2 years of age (P < .001) had positive varicella-zoster virus
      (VZV)-specific cellular immunity. VZV-specific antibodies in infants were
      significantly lower than those in children > or = 1 year old (P < .01) and > or =
      2 years old (P < .001). The possibility of subclinical reactivation was
      demonstrated by an increase in the specific cellular or humoral immunity (or
      both) in all of 6 infants who had negative specific cellular immunity. The low
      response of specific immunity and the immunologic evidence of reactivation in
      infants after chickenpox provide a possible explanation for the finding that
      chickenpox in infancy is a risk factor for herpes zoster.

PMID- 8158044
TI  - Maternal factors associated with prenatal transmission of ovine lentivirus.
AB  - Prenatal transmission of ovine lentivirus (OvLV) was studied in 85 eyes and their
      offspring. The animals were from a flock with endemic OvLV infection and 49 (58%)
      had serum antibodies to OvLV. Blood was collected from all lambs before they
      nursed. Using the polymerase chain reaction (PCR), OvLV DNA was detected in
      peripheral blood mononuclear cells of 13 (11%) of 117 lambs, including two sets
      of twins. Mothers with OvLV-infected lambs (n = 11) were younger (mean, 2.5
      years) and had fewer pregnancies (mean, 2.4) than seropositive ewes (3.2 years
      and 3.2 pregnancies; P < .05). Of mothers with OvLV-positive lambs, 4 had plasma
      antigenemia (mean, 31.3 +/- 2.1 ng/mL OvLV) in conjunction with indeterminate
      antiviral antibody responses by immunoblotting. These results suggest that
      maternal factors (age and parity) and host-virus interactions (antiviral antibody
      and antigenemia) are important risk factors in prenatal transmission of OvLV.

PMID- 8158045
TI  - The presence of M protein in nontypeable group A streptococcal upper respiratory
      tract isolates from Southeast Asia.
AB  - Previous studies have suggested that group A streptococcal strains from southeast
      Asia, serotypically different from temporally related North American and European
      isolates, may represent unrecognized M serotypes. Sixty non-M typeable group A
      streptococcal upper respiratory tract isolates from Thailand were evaluated for
      the presence of M protein using a modification of the direct serum bactericidal
      test. Of them, 59 (98%) grew rapidly in human blood. Typeability by T
      agglutination and opacity factor production did not influence their growth in
      blood. It was concluded that these isolates produce M protein and likely
      represent previously uncharacterized M serotypes. Identification of such non-M
      typeable strains is important in understanding the epidemiology and pathogenesis
      of group A streptococcal infections and their sequelae in areas of the world
      where they remain a significant health problem and will also be necessary in the
      development of a vaccine with global efficacy.

PMID- 8158046
TI  - Genotyping of Clostridium difficile isolates.
AB  - Arbitrarily primed polymerase chain reaction (AP-PCR) was used to genotype
      Clostridium difficile isolates from various sources. Four major molecular types
      were identified among strains from the American Type Culture Collection
      previously typed by serogroup and from isolates from patients at the University
      of California, Davis Medical Center, from a patient at a Utah institution, and
      from the environment. These groups contained subgroups that displayed, in
      addition to the common group bands, at least one unique band. Two strains
      isolated from patients at our institution had the same DNA banding patterns.
      These patients were hospitalized during the same period, raising the possibility
      of cross-infection through hospital contact or another common source. These
      results suggest that this AP-PCR approach will be useful in epidemiologic studies
      of C. difficile infections.

PMID- 8158047
TI  - Tumor necrosis factor is involved in the appearance of interleukin-1 receptor
      antagonist in endotoxemia.
AB  - To assess the role of tumor necrosis factor (TNF) in the appearance of
      interleukin-1 receptor antagonist (IL-1RA) in endotoxemia, 4 healthy humans were
      studied after a bolus intravenous injection of recombinant human TNF (50
      micrograms/m2). In addition, 8 healthy chimpanzees were investigated after a
      bolus intravenous injection of Escherichia coli endotoxin (4 ng/kg) with (n = 4)
      or without (n = 4) a simultaneous intravenous injection of a monoclonal anti-TNF
      antibody (15 mg/kg). TNF induced a pronounced rise in IL-1RA concentrations,
      becoming apparent after 1 h and peaking after 3 h (P < .05). The rise in IL-1RA
      after administration of endotoxin started 2 h later. Neutralization of the early
      endotoxin-induced TNF activity by anti-TNF caused a marked reduction in IL-1RA
      concentrations (P < .05). These results indicate that TNF is an intermediate
      factor in IL-1RA release in endotoxemia.

PMID- 8158048
TI  - Target imbalance: disparity of Borrelia burgdorferi genetic material in synovial
      fluid from Lyme arthritis patients.
AB  - Lyme arthritis is a late manifestation of Lyme disease that results in episodic
      synovial inflammation and swelling. Although this process is thought to be driven
      directly by the spirochetal etiologic agent, Borrelia burgdorferi, the organism
      itself has been recovered by culture only twice. In contrast, polymerase chain
      reaction (PCR) studies are usually positive. This apparent discrepancy in 19
      culture-negative synovial fluid specimens from 18 patients with Lyme arthritis
      was investigated. In all 19, DNA sequences characteristic of plasmid-encoded
      genes OspA and OspB were easily detected. However, despite equivalent or even
      superior analytic sensitivity for detection of cultured organisms, the reactivity
      of two genomic DNA targets was often weak or absent altogether in the clinical
      specimens. This apparent overrepresentation of B. burgdorferi plasmid sequences
      was found exclusively in clinical specimens and not in cultured organisms. The
      physiologic imbalance of genomic and plasmid DNA reactivity in B. burgdorferi
      infection may signal an underlying pathogenetic mechanism.

PMID- 8158049
TI  - Phenotypic and genotypic changes in a new clone complex of Neisseria meningitidis
      causing disease in The Netherlands, 1958-1990.
AB  - To characterize the phenotypic and genotypic changes that occurred in a new clone
      lineage of Neisseria meningitidis  (lineage III) in the Netherlands, the
      electrophoretic type (ET) was determined for 79 serogroup B isolates of serotype
      4 or subtype P1.4 (or both) obtained between 1958 and 1990 from patients with
      systemic meningococcal disease. Thirty-five previously described isolates were
      also included. After its appearance in 1980, lineage III started homogeneously
      with regard to both genotype (ET-24) and phenotype (B:4:P1.4). After 1984, other
      clones appeared in the lineage, and the various clones acquired other serotypes
      (serotypes 14 and 15) and subtypes (P1.2, P1.7, and P1.12), indicating frequent
      exchange of genetic material between clones. These results indicate that basing a
      serogroup B vaccine on outer membrane components from a single strain is not a
      valid strategy for the prevention of meningococcal disease.

PMID- 8158050
TI  - Natural genetic transfer of a putative virulence-enhancing mutation to
      Haemophilus influenzae type a.
AB  - Haemophilus influenzae strains of serotype a very rarely cause life-threatening
      infections. Examination of strains from the Gambia, West Africa, that caused
      septicemia, meningitis, or both revealed that a clone has emerged that carries a
      DNA deletion previously identified only in type b strains that is hypothesized to
      contribute to the special virulence of that serotype. This clone appears to have
      arisen by transfer of DNA between type a and type b strains, a transformation
      event that has happened more than once, as shown by the discovery Kenya, East
      Africa, of a clonally distinct type a strain bearing the identical deletion. The
      implications for the emergence of clinically important non-type b strains of H.
      influenzae are obvious.

PMID- 8158051
TI  - Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in
      monkeys: a pathogenic mechanism of tubal damage.
AB  - The role of delayed hypersensitivity in the pathogenesis of Chlamydia t
      trachomatis salpingitis was studied in the monkey "pocket" model. Pigtailed
      monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis
      organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal
      autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat
      shock protein (rhsp60) was injected into pockets either previously sensitized
      with C. trachomatis or not sensitized in the same monkey. Delayed-type
      hypersensitivity reaction was observed, characterized by mononuclear cell
      infiltration with peak reaction at 48 h. Injection of rhsp60 into the pockets of
      a naive animal did not induce inflammation. This study showed that C. trachomatis
      infection in monkeys induced delayed hypersensitivity, which is mediated by
      hsp60. Histologic findings of the salpinx were consistent with delayed
      hypersensitivity reaction observed in ocular C. trachomatis infection, further
      suggesting a similar pathogenesis for both salpingitis and trachoma.

PMID- 8158052
TI  - Use of DNA moderately repetitive sequence to type Aspergillus fumigatus isolates
      from aspergilloma patients.
AB  - Polymorphism of forty-seven sequential clinical isolates from 3 patients with an
      aspergilloma was analyzed. DNA from each isolate was digested with EcoRI and
      hybridized in Southern blots with a 32P-labeled nonribosomal DNA repetitive
      sequence. Most isolates from each patient displayed the same hybridization
      pattern. Southern blot patterns obtained with DNA repetitive sequences can be
      used to type clinical isolates of Aspergillus fumigatus and have shown that
      aspergilloma patients are most probably infected by a single strain.

PMID- 8158053
TI  - Polymerase chain reaction-based diagnosis of Onchocerca volvulus infection:
      improved detection of patients with onchocerciasis.
AB  - Definitive diagnosis of Onchocerca volvulus (Ov) infection requires the
      identification of the parasite in either the skin or subcutaneous nodules. These
      parasitologic approaches suffer from poor sensitivity. To assess the efficacy and
      utility of a polymerase chain reaction (PCR)-based diagnosis for Ov infection,
      skin snips were examined from 94 persons in an Ov-endemic region of Ecuador, and
      results were compared in a blinded fashion with those of a PCR assay based on the
      Onchocerca-specific repetitive DNA sequence, O-150. All 60 patients microfilaria
      positive on skin snip examination were positive in the PCR-based assay. In
      addition, 13 of 34 who were microfilaria-negative by skin snips were positive in
      the PCR assay. This suggests that the PCR-based assay is significantly more
      sensitive than current methods and overcomes many deficiencies of parasitologic
      and serologic methodologies in diagnosing active onchocerciasis.

PMID- 8158054
TI  - Cimetidine-induced rise in praziquantel levels in a patient with
      neurocysticercosis being treated with anticonvulsants.
AB  - A patient had neurocysticercosis complicated by a seizure disorder requiring
      anticonvulsants; previous praziquantel therapy (50 mg/kg/day) had failed to
      eradicate the disease. In an attempt to inhibit cytochrome P-450 metabolism of
      praziquantel, cimetidine (1600 mg/day) was coadministered. Before addition of
      cimetidine, the maximum concentration of praziquantel was 350 ng/mL; concurrent
      cimetidine administration increased the maximum concentration to 826 ng/mL. The
      elimination half-life increased from 1.7 h without cimetidine to 3.3 h with
      cimetidine and the area under the curve for the 12-h sampling period rose from
      754 ng.h/mL to 3050 ng.h/mL. Coadministration of cimetidine raises serum
      praziquantel levels and may be helpful in patients treated concomitantly with
      praziquantel and anticonvulsants.

PMID- 8158055
TI  - Immunoepidemiologic studies of Strongyloides stercoralis and human T lymphotropic
      virus type I infections in Jamaica.
AB  - Epidemiologic investigations of Strongyloides stercoralis and human T
      lymphotropic virus type I (HTLV-I) infections were conducted. Of 312 persons
      contacted, 209 (67%) provided blood and stool samples. Prevalences of S.
      stercoralis and HTLV-I antibodies were 26.8% and 8.1% (n = 198), respectively,
      and S. stercoralis larvae were detected in 4%. HTLV-I antibodies were
      significantly more common in persons positive for S. stercoralis larvae (10
      [58.8%] of 17) compared with seropositive larva-negative (4 [8.9%] of 45) or
      seronegative persons (9 [6.2%] of 145) (P < .002). IgE levels increased with age
      in S. stercoralis-seropositive persons who were HTLV-I negative (P < .002).
      However, there was an age-related depression of serum IgE in HTLV-I-positive
      positive persons (P < .003) that was sufficient to annul the IgE level-raising
      effect of S. stercoralis seropositivity. The data provide evidence that HTLV-I
      infection is associated with increased frequency of larvae in the stool of S.
      stercoralis-infected persons and suggest that the mechanism may involve
      suppression of the IgE response.

PMID- 8158056
TI  - Secretory IgA antibodies to Cryptosporidium parvum in AIDS patients with chronic
      cryptosporidiosis.
AB  - Immune mechanisms that may control Cryptosporidium parvum infection remain
      unknown. The role of T cell-mediated immunity is suggested by the chronic disease
      observed in AIDS patients and in athymic or CD4+ T cell-depleted mice. The role
      of specific antibodies is also unclear. This study sought to determine serum and
      secretory antibodies to C. parvum in patients infected with human
      immunodeficiency virus type 1 (HIV-1) with or without chronic cryptosporidiosis.
      C. parvum-specific antibodies and specific secretory antibodies were determined
      by ELISA in saliva and sera from 50 HIV-1-infected patients, 27 healthy adults,
      and 21 healthy children. Despite lower CD4+ lymphocyte counts, patients with
      chronic cryptosporidiosis had increased levels of C. parvum-specific antibodies
      in saliva and serum and higher specific secretory antibody levels in saliva than
      did controls. Persistence of protracted diarrhea despite high levels of both
      serum and secretory antibodies suggests that specific secretory antibodies are
      not sufficient to control this protozoan parasite infection of intestinal mucosa.

PMID- 8158057
TI  - Prospective evaluation of red man syndrome.

PMID- 8158058
TI  - Treponemal infection and pregnancy outcome in west Africa.

PMID- 8158059
TI  - A high false-positive rate of tuberculosis associated with Aplisol: an
      investigation among health care workers.

PMID- 8158060
TI  - Transplacental passage of hepatitis B virus DNA from hepatitis B e antigen
      negative mothers and delayed immune response in newborns.

PMID- 8158061
TI  - Hepatocellular carcinoma: lack of association with a unique hepatitis C virus
      nucleotide sequence.

PMID- 8158062
TI  - Mononuclear cell subpopulations in human immunodeficiency virus (HIV)-positive
      versus HIV-negative patients with visceral leishmaniasis.

PMID- 8158063
TI  - Lack of cross-protection against diarrhea due to Vibrio cholerae O1 after oral
      immunization of rabbits with V. cholerae O139 Bengal.

PMID- 8158064
TI  - [Simultaneous one- or two-stage restoration of the vertebral and carotid
      arteries].
AB  - Surgery of the vertebral artery is controversial. Few teams performed this
      procedure routinely. The usefulness of the vertebral artery surgery is even more
      questionable when carotid artery lesions are associated. In such cases many
      surgeons claim that carotid artery surgery alone can relieve symptoms of
      vertebrobasilar insufficiency. In deciding whether or not to perform vertebral
      artery surgery three questions are essential. First, is a restauration of one or
      both vertebral artery necessary in this situation? Second, will combined surgery
      increase the risk of mortality and morbidity? Third what technique should be used
      and in what order?

PMID- 8158065
TI  - [Value of the prosthetic patch after carotid endarterectomy].
AB  - INTRODUCTION: Carotid patching after carotid endarterectomy remains a subject of
      controversy. However the recent medical literature shows that carotid patching
      lowers the incidence of both residual stenosis and early restenosis. Carotid
      patching seems also to lower the incidence of postoperative carotid occlusion.
      Some authors advocate systematic patching, others recommend a more selective use
      of carotid patching, among patients with small caliber carotid artery and among
      those with restenosis. STUDY: We have realized this study to determine (1) the
      incidence of restenosis after direct closure in patients with internal carotid
      artery of more than 3.5 mm internal diameter, (2) the adequate size of the patch
      in carotid arteries of less than 3.5 mm interval diameter (3), the adequate
      material to use for carotid patching. To answer these questions, we have done a
      prospective study of 188 carotid endarterectomy comparing direct closure (Group
      A), saphenous patch (Group B), and prosthetic Gore-Tex patch (Group C) with
      randomization between saphenous and prosthetic patch. RESULTS: In this study we
      were unable to show any difference among the three groups concerning
      postoperative mortality and neurologic complications. However we have been able
      to show more residual stenosis in group A than in groups B and C. One saphenous
      patch rupture occurred in Group B. After one year follow-up, five out of 43
      restenosis occurred in Group A (11.6%). The rate of restenosis in groups B and C
      was 1.5% (2/135). In group B, six patients (8.7%) had a dilatation of the
      saphenous patch of more than 50% of their initial diameter. CONCLUSIONS: In this
      study, carotid patch seems to lower the incidence of residual stenosis and early
      restenosis in small diameter internal carotid arteries. Carotid patching with a 5
      mm diameter PTFE patch seems to be the ideal choice after carotid endarterectomy.
      Furthermore, prosthetic patching carry no risk of dilatation or rupture and spare
      the saphenous vein.

PMID- 8158066
TI  - [Bilateral stenosis of the renal arteries: multiple bypasses].
AB  - Bilateral ostial renal arterial stenoses are in fact atheromatous lesions of the
      aortic wall. These anatomic features must be considered for the treatment of such
      lesions. It can be achieved by bilateral renal bypass grafting with the
      concomitant replacement of the aorta when necessary. This combined surgery
      carries a certain operative risk, which has been notably lowered with the recent
      advances in anaesthesiology and intensive care. We consider this combined renal
      and aortic surgery is easier and safer than transaortic endarterectomy.

PMID- 8158067
TI  - [Bilateral stenosis of the renal arteries: transaortic endarterectomy].
AB  - Transaortic renal endarterectomy with infra-renal aortic prosthetic graft may be
      used to treat combined aortic and renal atherosclerosis. We present herein the
      technics we used in seven patients, which represented 0.4% of our aortic
      revascularizations and 15% of our combined aortic and renal revascularizations.
      All these patients were hypertensive and four had a mild preoperative renal
      insufficiency. Post-operatively there were no death and the morbidity rate was
      12%. Morphological assessment showed no renal or limb graft occlusion. During the
      follow-up there were three deaths, one limb graft occluded. All renal arteries
      remained patent with improvement of hypertension in 70% and stabilisation of the
      renal function in all. In carefully selected cases, transaortic renal
      endarterectomy is a safe and efficient method of treatment of combined aortic and
      renal atherosclerotic disease.

PMID- 8158068
TI  - [Aneurysms of branches of the renal artery: surgery in situ].
AB  - Renal artery aneurysms (RAA) are rare lesions, often associated with
      hypertension. In order to evaluate the benefit in terms of blood pressure of
      elective cure of a fibrodysplastic renal artery aneurysm in hypertensive
      patients, 22 patients were studied retrospectively. With a mean follow-up of 66
      months, correction or improvement of hypertension was obtained in all patients
      with an isolated aneurysm or an aneurysm associated with haemodynamic lesions of
      the renal artery, treated at the same time, but only 40% of cases when the
      aneurysm was associated with non-haemodynamic lesions. Direct criteria
      attributing the hypertension to the aneurysm were generally absent.

PMID- 8158069
TI  - [Aneurysms of branches of the renal artery: surgery ex vivo].
AB  - Extra corporeal replacement of the renal artery for the treatment of complex
      renal artery diseases offers numerous advantages: safe approach for the branches
      of the renal artery and division of the intra-hilar arteries, easy repair and
      sutures, excellent quality of intra-operative arteriogram, easy repair of venous
      damage, excellent renal preservation. These advantages and the excellent long
      term results justify extra-corporeal surgery as the procedure of choice for the
      treatment of complex renal artery disease.

PMID- 8158070
TI  - [Renal artery occlusion: surgical revascularization].
AB  - Five patients were treated for renal artery occlusion, as a result of embolism (2
      patients), thrombosis of a stenosed vessel (1 patient) or acute occlusion during
      percutaneous transluminal angioplasty (2 patients). Three patients had poorly
      controlled hypertension. One patient was anuric. Patients were treated
      operatively in 4 cases and non operatively in 1 case. There were no death and no
      renal failure that necessitated chronic hemodialysis. All bypasses except one
      remained patent. Blood pressure increased in the patient with the bypass
      occlusion and was reduced in all four other patients. Renal artery occlusion does
      not necessarily cause renal infarction. Evaluation of renal viability is
      necessary before decision of revascularization. Surgical exploration seems the
      best predictive factor.

PMID- 8158071
TI  - [Renal artery occlusion: percutaneous revascularization].
AB  - The value of percutaneous revascularization of acute or chronic occluded renal
      arteries is demonstrated in 9 cases. Recanalization and dilatation was
      technically successful in 6 patients. The authors stress the importance of
      anatomo-radiologic criterion for successful recanalization. This technic is an
      attractive alternative to surgery specially in short occlusion.

PMID- 8158072
TI  - [Long occlusion of the superficial femoral artery: revascularization by compliant
      prosthesis].
AB  - We believe that the use of prosthetic grafts is justified in the treatment of
      long occlusions of the superficial femoral artery. However the surgery should
      only be done in cases where patients are suffering from severe claudication and
      in cases of critical ischemia of the lower limbs. We report herein the mid-term
      results of an European multicentric prospective study of a new prosthesis which
      is compliant, ultraporous and made of polycarbonate. We found a patency similar
      to that obtained with PTFE grafts as reported in the literature. In these
      indications, the choice of prosthetic grafts allows for a better management of
      atherosclerosis arterial disease. Thus autologous saphenous veins are still
      available to treat coronary artery disease or femoro tibial occlusion which
      remain a frequent evolution in that type of patient.

PMID- 8158073
TI  - [Long occlusion of the superficial femoral artery: revascularization by venous
      graft].
AB  - In long occlusions of the superficial femoral artery, possibilities of
      revascularization depend on the patency of the above-knee popliteal artery. In
      case of occlusion of the above-knee popliteal artery, the distal anastomosis is
      to be performed at the below-knee level or more distally; in this situation,
      studies demonstrate a clearcut superiority of venous bypasses over prosthetic
      bypasses. Patency of the above-knee popliteal artery allows to perform a shorter
      bypass avoiding to cross the knee joint; given comparable results between venous
      and prosthetic above-knee bypasses in certain series, several authors advocated
      the preferential, if not systematic use of prosthetic materials at this level;
      this attitude having the advantage of preserving the saphenous vein for later
      coronary or distal grafting. A critical analysis of studies advocating this
      therapeutic option reveals that results of prosthetic and venous above-knee
      bypasses are equivalent in only very restrictive clinical situations
      (claudication, good runoff) and for follow up less than 3 years; beyond this
      follow up, the use of a prosthesis increases the number of secondary procedures
      necessary for maintaining or restoring patency and for this reason increases
      slightly the overall mortality owing to the operative mortality associated with
      each reoperation. Apart from rare cases represented by fragile and high-risk
      patients, whose lifespan is likely to be short and in whom a quicker operation is
      advisable, indications of the use of prosthetic grafts depend on the limits of
      the use of the saphenous vein generated by a poor quality or an insufficient
      diameter.

PMID- 8158074
TI  - [Short occlusion of the superficial femoral artery: argument for medical
      treatment].
AB  - In cases of superficial femoral artery occlusion, the choice between endovascular
      therapy and medical rehabilitation is only relevant in the presence of an
      occlusion shorter than 10 cm. Thirty to fifty per cent of patients who had an
      endovascular procedure will have their artery patent for one year. The true
      benefit of this result can only be assessed by taking into account the efficiency
      of the medical treatment, the costs and the risks of the endovascular treatments.
      Endovascular techniques should be reserved for selected patients: psychologically
      or socially incapable of accepting the slowness and the restraints of the medical
      treatment.

PMID- 8158076
TI  - [Popliteal aneurysm and leg ischemia: thrombolysis first].
AB  - Popliteal aneurysms may threaten the viability of lower limbs, especially in the
      case of occlusion and poor run-off. In case of acute ischemia, thrombolysis can
      be used before surgery to clear the tibial arteries and enhance the results of
      subsequent bypasses. The procedure starts with an arteriography to show the
      arterial tree, then a recanalization is attempted. By means of a microcatheter
      pushed into the thrombosis, Heparin (1000 Units/h) and Urokinase (4,000 Units/h)
      are injected in situ. Arteriograms are repeated in order to control the placement
      of the catheter. Anticoagulant and fibrinolytic doses are biologically surveyed.
      Local and general complications are rare with the new techniques of fibrinolysis.
      Hemorrhagic complications following surgery are low despite the previous
      fibrinolytic treatment. Better success rates of bypasses, performed to relieve
      acute ischemic complications of popliteal aneurysms, should be achieved with this
      new modality of treatment.

PMID- 8158075
TI  - [Popliteal aneurysm and leg ischemia: surgery first].
AB  - The treatment of symptomatic popliteal aneurysms is debated should local
      fibrinolysis or surgery first be used first? The authors report their experience
      in the treatment of 90 popliteal aneurysms in 66 patients. In this series were
      only examined those aneurysms with either acute ischaemia 12 (27%) or sub-acute
      ischaemia 21 (45%). The treatment of those cases with acute ischaemia was
      surgical for all, allowing salvage in all cases. Sub-acute ischaemia was treated
      with either: a surgical bypass with exclusion of the aneurysm in 7 cases, or
      lumbar sympathectomy in 7 cases, or medical treatment in 6 cases or local
      fibrinolysis for distal ischaemia in one case only. There was no peri-operative
      mortality, only one amputation was required (5%) (J Mal Vasc 1994; 19, Suppl. A:
      pages 150-153).

PMID- 8158077
TI  - [Peroperative monitoring of femoral-popliteal vein bypasses by angioscopy].
AB  - For the past few years, arteriography has been the gold-standard examination for
      the intra-operative control of femorodistal bypass grafts. Angioscopy is an
      alternative method permitting to assist the preparation of the venous graft, and
      to control the quality of the lumen as well as the anastomoses at the end of the
      procedure. The techniques employed and the results published in the medical
      literature are analysed in this study. After completion of this survey, it seems
      that angioscopy and arteriography used as means of control of infra-inguinal
      arterial reconstructions can be compared regarding the facility of the
      examination, the time necessary for its realisation, and its cost. However
      angioscopy is more sensitive than arteriography for the diagnosis of technical
      imperfections that may result in immediate failure of infrainguinal bypasses.

PMID- 8158078
TI  - [Distal arteritis of the legs: de-obstruction of the popliteal trifurcation].
AB  - Conventional arteriograms for critical leg and foot ischemia frequently do not
      opacify the popliteal artery and its branches of division. We have studied the
      patency of the popliteal artery on amputated limb and we have seen that in a
      great number of cases, it was possible to retrieve fresh clots from the popliteal
      artery in order to obtain a optimum outflow and to perform a femoro-popliteal
      bypass. Since the completion of this study, we systematically explore the
      popliteal artery surgically in case of critical leg and foot ischemia even in the
      cases where arteriogram failed to demonstrate a patent artery. This aggressive
      surgical management resulted in a 78.5% five year limb salvage rate.

PMID- 8158079
TI  - [Distal arteritis of the legs: endovascular treatment].
AB  - Femoro-tibial bypasses are not always feasible in patients presenting with
      "critical" chronic ischemia. The results of endovascular therapies carried out
      over a 2-year period are analyzed. Twenty-three patients with critical ischemia
      (rest pain 13%, gangrene 87%) had 25 procedures on 29 leg arteries: percutaneous
      transluminal angioplasty in 17 arteries, rotational atherectomy in 10 arteries,
      laser recanalization (1 artery), directional atherectomy (1 artery). The hospital
      mortality rate was 4.3%. The cumulative patency and limb salvage rates were
      respectively 51% and 77% at 6 months, 34% and 71% at 12 months. Candidates for
      tibial-peroneal endovascular techniques should have a threatened limb, as long as
      the consequences of failed procedures on patients presenting with claudication
      can be disastrous, and as long as mid-term patency rates reported in the
      literature are not fair enough. In localized stenosis or short occlusions with
      adequate runoff, endovascular techniques are a good alternative to femorotibial
      bypasses for limb salvage. In diffuse lesions with no possibility of bypass,
      endovascular techniques can facilitate limb salvage, even if the mid-term
      arterial patency rate is poor. When conventional therapies cannot face critical
      ischemia, endovascular therapies can provide a fair limb salvage rate.

PMID- 8158080
TI  - [Distal arteritis of the legs: lumbar sympathectomy].
AB  - Among atheromatous occlusive arterial disease of the lower limbs, chronic sub
      popliteal arterial occlusions refer an heterogenous group of patients. In this
      medical condition, lumbar sympathectomy constitutes a classical possible
      treatment. Actually, the beneficial effect of sympathectomy has never been
      confirmed by controlled randomised trials. In this particular and uncomfortable
      situation, it is only possible to list non indications for sympathectomy:
      asymptomatic patient, claudication, critical ischemia, limb salvage, and
      combination with vascular surgery. Lumbar sympathectomy deserves a controlled
      evaluation in patients with a small foot ischemic ulceration without hemodynamic
      critical ischemia i.e. systolic toe pressure > 30 mm Hg and/or ankle systolic
      pressure > 50 mm Hg.

PMID- 8158081
TI  - Endovascular therapy of lower extremity arterial occlusive disease: are advanced
      generation devices worth the cost?
AB  - Endovascular recanalization has a relatively small but important role in the
      treatment of arterial occlusive disease. The balloon angioplasty catheter remains
      the most versatile and successful tool for transluminal therapy. A multitude of
      advanced generation devices have been developed in recent years; of these,
      intravascular stents are gradually emerging as most useful and capable of
      enhancing the results of angioplasty in selected instances.

PMID- 8158082
TI  - [Reverse endarterectomy of the internal carotid].
AB  - We have described an original technique of eversion carotid endarterectomy which
      has been performed in two series of patients. In the first series the patients
      were operated on in Angers. They were 65 carotid stenosis in 56 patients with a
      mean follow-up of 27 months (18-36 months). In the later series, the patients
      were operated on in Lyon. They were 51 carotid stenosis in 43 patients with a
      follow-up from 1 to 24 months. The two series were comparable in term of symptoms
      and grade of stenosis as determined by duplex-scan and arteriography. The
      technique which has been previously described is safe and presents a lot of
      advantages over classical endarterectomy or vein graft. We observed no
      postoperative neurological deficit and no postoperative thrombosis. Two residual
      stenosis (1.7%) were measured at 30% but they did show any impairment during two
      years of follow up in the first series. Eversion endarterectomy of internal
      artery is a safe and deficient alternative to others techniques in the surgical
      treatment of atherosclerosis stenosis of internal carotid artery.

PMID- 8158083
TI  - [Internal carotid artery surgery using a venous graft].
AB  - Thromboendarterectomy is the most popular technique of carotid restoration for
      atheromatous lesions. In some cases, endarterectomy may be difficult or hazardous
      to perform, when atherosclerotic lesions involve the proximal common carotid
      artery and/or the distal internal carotid artery, when they are radiation
      induced, and when they are associated with fibromuscular dysplasia, loops or
      kinking. In other cases, result of endarterectomy may be unsatisfactory, because
      of a traumatic lesion of the arterial wall during endarterectomy, or a stenosis
      of the arteriotomy closure. Postoperative and late restenosis and occlusion rate
      range between 10 and 50% after primary closure of the carotid arteriotomy. Some
      of these complications may be reduced by alternative techniques such as eversion
      endarterectomy or patch angioplasty closure. Reversed saphenous bypass may also
      be performed. In our experience, only suitable autologous greater saphenous vein
      shall be harvested, including adequate length, absence of valves, diameter
      greater than 4 mm, and excellent wall texture. Distal anastomosis on the internal
      carotid artery shall be performed end-to-side with ligation of the internal
      carotid stump, and not end-to-end. Thus, in that location, venous grafts have
      excellent long-term patency with less than 5% late restenosis or occlusion rate.
      Thus, venous graft bypass may be an alternative technique to carotid
      endarterectomy, especially in young patients and women, who are more often
      exposed to late complications.

PMID- 8158084
TI  - [Carotid and aortic lesions: two-stage surgery].
AB  - The problem of chronology between different surgical acts is at stake when a
      patient suffering from carotid and aorto-iliac or femoropopliteal diseases
      requires surgery. The joint operation increases surgical risk and its practice
      penalizes the surgeon. Sequential surgery is safer. It does not increase the risk
      of a adverse evolution of the diseases areas which has not been operated on at
      time of the first operation.

PMID- 8158085
TI  - [Carotid surgery without systematic preliminary angiography. 402 patients treated
      by surgery between 1986 and 1992].
AB  - Ultrasonography of the carotid bifurcation is a high performance technique for
      the detection of carotids stenosis. Associated with Doppler and echography,
      ultrasonography offers a means of precisely evaluating atheromatous stenoses of
      the bifurcation. The degree of narrowing can be calculated from the pulsed
      Doppler recordings and colour echo-Doppler measurements, reducing the subjective
      interpretation factor (the operator-dependent nature of the exploration is no
      longer related to data collection). Most severe stenoses can be diagnosed with
      these techniques. The question now is whether carotid angiography is still
      necessary to establish the indication for surgical endarterectomy. We attempted
      to give an answer based on our prospective series of 402 endarterectomies of the
      carotid bifurcation performed between 1986 and 1992 without prior routine
      angiography. Arteriography was performed occasionally in the pre-operative work
      up but was limited to cases in which the ultrasonography was judged insufficient.
      We observed a mortality of 0.25% and a morbidity of 0.5%. This diagnostic
      approach is justified by its lower cost and reduced risk due to arteriography. In
      addition, unidentified arterial lesions downstream have little or no effect on
      indications and outcome.

PMID- 8158086
TI  - [Is surgery of a carotid lesion possible without arteriography?].
AB  - Cerebro-vascular angiography has been for a long time the standard for operative
      decision. It has been ten years since the development of duplex scanning has
      allowed a non invasive approach of the diagnosis. Several authors have reported
      series of endarterectomy, some of them without preoperative arteriography. The
      authors remind us of the different arteriography procedures, their advantages and
      their risks and compare them to the results of duplex scanning: they admit that
      it is possible to do a carotid endarterectomy without preoperative arteriography.
      They define their indications but they are persuaded that arteriography is an
      excellent procedure and the rate of neurologic complications due to the technique
      is lower than 0.5%.

PMID- 8158087
TI  - [Subclavian vein thrombosis: medical treatment].
AB  - Thromboses of the subclavian vein are rare. However there is a higher incidence
      due to the increasing use of central venous catheters and pacemakers. Thoracic
      outlet syndrome is no longer the main cause. Thromboses may be clinically
      apparent, however when they are caused by the insertion of a catheter, thromboses
      may be symptom-free. Phlebography is the gold standard for the diagnosis. B mode
      ultra-sounds may give false results in that particular location. The optimum
      treatment of subclavian thromboses should prevent the occurrence of pulmonary
      embolisms, and the development of post-thrombotic syndrome. Heparin followed by
      anti-vitamin K meets these two objectives in the majority of cases. The risks of
      thrombolytic therapy is, in our opinion, unacceptable to promote thrombolysis to
      treat upper limb venous thrombosis. Surgery is indicated in cases of phlematia
      caerulea which are extremely rare, and in cases of septic thrombosis. The
      preventive treatment of the opposite side of a symptomatic thoracic outlet
      syndrome, is questionable, except in the case where the findings of the clinical
      examination, B mode ultrasound and phlebography results, are in favor of a
      intermittent compression of the vein with a risk of thrombosis.

PMID- 8158088
TI  - [Subclavian vein thrombosis: surgical treatment].
AB  - Subclavian vein thromboses are relatively uncommon and presents therapeutical
      problems related to their etiology and the clinical consequences. Although
      primary thromboses are frequently opposed to secondary thromboses (particularly
      after catheters) they are frequently intermingled. Decision for surgery should be
      based on anatomical features, mechanisms of thrombosis and their clinical
      consequences.

PMID- 8158089
TI  - ["Logic" and doubts in the surgery of associated carotid and vertebral lesions].
AB  - Combined vertebral artery and carotid artery surgery may be performed in patients
      with proximal subclavian or vertebral artery stenosis provided that general
      anesthesia is not contraindicated? Others indications may be considered in
      patients with proved arterial thrombo-embolism or in patients for whom
      arteriography, cerebral angioscintigraphy and ultrasound velocimetry enable the
      physician to suspect a cerebral low flow and the lack of collateral pathways
      between the posterior and anterior cerebral system.

PMID- 8158090
TI  - [Loops and folds of the carotid and vertebral arteries: indications for surgery].
AB  - Tortuous variants of the carotid or vertebral morphology are apparent on 10 to
      43% of angiograms. It is probable that the incidence of these anomalies is lower
      in the normal population. Rarely, their etiology is congenital explaining the
      existence of some pediatric cases. The etiology of most cases is acquired and
      linked with hypertension, atheroma and aging. Basically consisting of an excess
      of length of the common or the internal carotid artery, the tortuosity may take
      the form of simple or multiple kinking, coiling or looping. Isolated, these
      anomalies are asymptomatic in a large majority of the cases. However,
      hemispheric, vertebrobasilar or ocular ischemic symptoms may be caused by them
      through a thromboembolic or hemodynamic mechanism. Moreover, given their frequent
      association with atherosclerotic occlusive lesions, their participation in the
      production of ischemic symptoms is not easy to determine. Although not yet
      investigated by prospective randomized studies, symptomatic isolated of kinking
      or coiling of cerebral arteries are amenable to surgical revascularization in
      order to prevent stroke or blindness. Besides, the endarterectomy of
      atherosclerotic occlusive lesions of tortuous carotids requires a technical
      adaptation.

PMID- 8158091
TI  - [Loops and folds of the carotid and vertebral arteries: indications for surgery].
AB  - We present our results of surgical correction of non-atheromatous redundant
      internal carotid arteries. From 1986 until 1992, we performed 1641
      endarterectomies of the internal carotid artery, and in the same time we
      diagnosed 49 elongations in 42 patients. In 25 cases, indication for surgery was
      given and reconstruction was performed by shortening of the internal carotid
      artery, using resection and reanastomosis associated in one third of the cases
      with a patch. Nineteen patients (76%) were symptomatic, four patients (16%)
      presented a preoperative stroke and 2 patients (8%) were asymptomatic. All the
      patients were neurologically monitored by the use of somatosensory evoked
      potentials. One patient needed an intraluminal shunt because of loss of evoked
      potentials. No patient died in the postoperative period. One stroke occurred,
      concomitantly to a thrombosis of the internal carotid artery, but with totally
      reversible clinical symptoms after reoperation. We noted one transient ischaemic
      attack. We recommend operative treatment in symptomatic patients or when the
      stenosis is higher than 60%. A stenosis under 60% should be operated in the case
      of a contralateral occlusion. We propose a classification of redundant arteries
      based on the importance of the stenosis. The exact assessment of the stenosis is
      the determining factor in the diagnosis and is of primordial importance when
      indicating surgery.

PMID- 8158092
TI  - [Is in depth diagnosis important in renal artery stenosis?].
AB  - The experimental discovery of the pathophysiological relationship between renal
      artery stenosis and arterial hypertension was historically reported (1934) before
      the clinical description of the disease in human patients (1950). The
      experimental model explains the relation between renal ischemia, renal endocrine
      activation, and morphological alterations of the homo and contralateral kidneys.
      In particular, the experimental model improves the understanding of the evolution
      of renovascular disease. In human patients, renal artery stenosis does not always
      lead to clinical disease. Because of the frequency of arterial hypertension,
      there is not always a clear relationship between hypertension and renal
      insufficiency or renal artery stenosis. Therefore a complete diagnosis of renal
      endocrine and exocrine function is needed to understand this relation before
      deciding on the therapeutic approach. This diagnosis is made by exploration of
      the renal renin-angiotensin axis, its pharmacological blockade and the response
      of the excretory function. This approach corresponds to the clinical description
      of the evolution of the disease; the peripheral and renal vein renin assays; the
      pressure and scintigraphic response to converting enzyme inhibition and renal
      morphological definition by echography and CT scan. This pathological approach
      permits a rational choice of the therapeutic indication: non-intervention,
      specific medical treatment, endovascular or surgical revascularization or
      nephrectomy.

PMID- 8158093
TI  - [Renal artery stenosis and aorto-iliac restoration: is it necessary to do
      extensive evaluation?].
AB  - In patients with aortoiliac disease and a stenosis of one or two renal artery,
      renal hypertension is rarely the sole mechanism of the elevated blood pressure.
      The preservation of nephron mass being the aim of the renal revascularization, we
      firmly believe that only three tests are required for the operative decision:
      renal ultrasonography, nephroscintigraphy and global and selective aortography.

PMID- 8158094
TI  - [Approach to aortic aneurysms including the renal arteries: intra-abdominal
      method].
AB  - Transperitoneal incision is the usual way to approach the abdominal aorta, either
      electively or in emergent cases. Supine position of the patient is more
      comfortable for him, for the anaesthesiologists and for the surgical team. The
      exploration of the intra-peritoneal organs which is the first stage of the
      operation, may find pathological processes such as infectious diseases or cancer
      which contraindicate the vascular procedure. The right tributaries of the aorta,
      the hepatic artery, the renal artery and the common iliac artery, are only easily
      approached by a transperitoneal route. In order to control the upper part of
      pararenal aneurysms, four manoeuvres may be used:--mobilization of the left renal
      vein with ligation of the left genital and suprarenal veins--dissection of the
      coeliac aorta through the crux of the diaphragm,--dextro-rotation of the spleen,
      the tail of the pancreas, and the left part of the colon which enables the supra
      renal aorta and the visceral arteries to be approached,--mobilization of the
      duodeno-pancreas to approach the origin of the superior mesenteric artery, and
      the full length of the right renal artery. The closure of the abdominal incision
      is easy. No prospective randomized study has proved, up to now, the superiority
      on the extra-peritoneal route compared to the transperitoneal approach in terms
      of post-operative respiratory or general complications.

PMID- 8158095
TI  - [Approach to aortic aneurysms including the renal arteries: retroperitoneal
      method].
AB  - A pararenal aneurysm is a rare type of an abdominal aortic aneurysm. The authors
      report 25 cases out of 429 abdominal aneurysms. The diagnosis was based on a CT
      scan and subsequent biplane arteriography. The most common type was the dorsal
      proximal aortic dilatation, involving the origin of 1 or 2 renal arteries. A
      retroperitoneal approach was used in 18 of the 25 patients. The most common
      complication was the retroperitoneal hemorrhage, necessitating reintervention.
      None of these patients died or developed renal insufficiency despite a suprarenal
      clamping during the proximal reconstruction.

PMID- 8158096
TI  - [Ostial stenosis of the renal arteries: results of surgery].
AB  - Surgery and percutaneous balloon are two contrasting methods for the treatment of
      renal artery stenosis. Surgical revascularizations offer excellent long term
      results with a 70% to 90% five year patency rate wherever the location of the
      lesion on the renal artery. Long term results of transluminal angioplasty are
      strongly correlated with the anatomo-radiological features of the lesions. From
      their own experience and after a literature review, the authors conclude that:
      For lesions located on the trunks of the renal artery, results of surgery and
      transluminal angioplasty are equivalent. For lesions involving the ostium of the
      renal artery, the failure rate is high and restenosis are frequent with
      angioplasty. In that case, surgery is a proper choice which offers better
      immediate and long term results.

PMID- 8158097
TI  - [Ostial stenosis of the renal arteries: treatment by angioplasty].
AB  - In a series of 50 patients (22 females, 28 males); 52 ostial renal artery
      stenoses were treated by transluminal balloon angioplasty. The mean age of
      patients was 66 years (range 36-81); mean arterial pressures were 181 mmHg for
      the systolic pressure and 87 mmHg for the diastolic pressure. The mean level of
      serum creatinine was 179 mumol/l +/- 128. An immediate success was obtained in
      86.5% (residual stenosis of 26%). There were 7.6% of immediate failures and 13.5%
      of residual stenosis above 50%. Mortality within 1 month was observed in 2
      patients. Morbidity included one aortic dissection and 5 cholesterol embolisms.
      After a mean follow-up of 10 months, 78% of the series were controlled: 66.6%
      exhibited a residual stenosis below 50%, 25.9% had restenosis and 7.4% had an
      occlusion of the renal artery. Since patients with ostial renal artery stenosis
      constitute a high surgical risk group, transluminal balloon angioplasty might be
      considered as an acceptable and safe alternative treatment.

PMID- 8158098
TI  - Renal artery stenosis surgery: aorto-renal by-pass.
AB  - A variety of operative techniques can be used for renal revascularization. This
      discussion summarizes my indications, technique and results of direct aorto-renal
      bypass. I currently use aorto-renal bypass for all distal main renal artery and
      branch renal artery reconstructions in the treatment of both atherosclerotic and
      fibromuscular dysplastic lesions. Early technical success occurs in over 97% of
      cases. Sustained late success without graft stenosis or degeneration for up to 23
      years has been documented in over 88% of cases. In my experience, aorto-renal
      bypass remains the preferred method for renal revascularization in over one-half
      of all patients.

PMID- 8158099
TI  - Surgery of the renal artery: hepato and spleno renal bypass.
AB  - Hypertension is a devastating disease that affects an estimated 20 million
      Americans per year and predisposes them to cardiac, cerebral and renal disease.
      The need to discover and treat the surgically curable forms of hypertension is
      underscored by the lethal effects of this entity. Restoration of renal blood flow
      to a stenotic or occluded renal artery for the management of poorly controlled
      renovascular hypertension or deteriorating renal function is a proven therapeutic
      modality. The technical advances of digital subtraction angiography, angiotensin
      converting enzyme inhibitor challenge, balloon angioplasty and alternative
      surgical bypass procedures have inspired a more aggressive approach to the
      diagnosis and treatment of higher risk patients with atherosclerotic disease and
      the application of bench surgery for difficult branch segmental disease. The
      indications for surgical correction of patients with atherosclerosis are more
      limited, owing to the presence of commonly associated diseases of senescence, and
      the presence of extrarenal vascular disease. Treatment with more effective new
      potent antihypertensive drugs is warranted initially in this population and may,
      in fact, be preferred in patients with generalized atherosclerosis. Our own poor
      results with percutaneous transluminal angioplasty for atherosclerotic lesions
      has prevented us from offering this option to patients with classic renal ostial
      lesions which are in essence an aortic disease that does not respond to this
      modality. The less common short mid-renal artery disease without a significant
      aortic component frequently responds to balloon dilatation if skillfully applied.

PMID- 8158100
TI  - Toxic effects of beta-aminopropionitrile treatment on developing chicken skin.
AB  - beta-aminopropionitrile (BAPN), a compound that inhibits crosslinking of
      collagen, has been widely used to examine the function of collagen in developing
      tissues. We used BAPN to examine the function of collagen during the formation
      and patterning of feather rudiments in embryonic chicken skin. Organ cultures of
      skin were treated with different concentrations of BAPN and examined for changes
      in morphology, histology, and extent of collagen crosslinkage. Increasing
      concentrations of BAPN led to striped patterns of feather rudiments, increases in
      feather rudiment diameter, and increases in skin thickness in cultured skin.
      These changes in morphology were paralleled by a progressive decrease in collagen
      crosslinkage as the concentration of BAPN was increased. However, these changes
      were also paralleled by an increase in cell death in the epidermis. Culture of
      monolayers of separated epidermal and dermal cells in the same concentration
      range of BAPN that altered feather development in the organ cultures showed that
      BAPN killed epidermal cells but not dermal cells. Our results suggest that
      developmental alterations caused by BAPN may, in some cases, be due to acute
      toxicity to specific cell types, and not simply to inhibition of collagen
      crosslinkage.

PMID- 8158101
TI  - Patterns of DNA synthesis and mitotic activity during the intermoult of Daphnia.
AB  - Among insects, the epidermal cell cycle pattern is related to the type of
      ontogenetic development. In taxa undergoing complete metamorphosis, cells are
      commonly maintained in the G2 stage of interphase between bouts of cell division.
      In crustaceans, as in insects exhibiting incomplete metamorphosis, it is believed
      that cells ordinarily remain in G1 for much of the intermoult, with DNA
      replication occurring late in the moult cycle followed closely by cell division.
      The present study reveals a differing pattern of epidermal cell division in two
      distantly related members of the cladoceran crustacean genus Daphnia. Cell cycle
      kinetics were examined in the last juvenile instar of each species using DNA
      content determinations and estimates of mitotic frequency. These analyses confirm
      that each epidermal cell possessed the diploid DNA amount, completed a single
      cell cycle, and remained in G1 for the majority of the instar. However, DNA
      replication occurred shortly after moulting and was followed by intense mitotic
      activity so that cell proliferation was restricted to a short period soon after
      ecdysis. Cell densities during the instar increased by approximately 60 and 100%
      for D. pulex and D. magna, respectively.

PMID- 8158102
TI  - A Xenopus maternal effect mutant gene affects oocyte meiotic reinitiation and
      fertilization.
AB  - No cleavage (nc) is a maternal effect mutant gene, recessive and sex limited. It
      affects the eggs laid by homozygous mutant females, independently of the male
      genotype. Contrary to normal oocytes, following germinal vesicle breakdown (GVBD)
      during maturation, the transient microtubular array (TMA) is not formed, nor are
      the meiotic spindles. Cytoplasmic asters with condensed chromosomes are present
      in the majority of oocytes, as well as microtubular bundles and sometimes
      cytoplasmic spindle-like asters. These mature oocytes exhibit a disturbance in
      yolk platelet arrangements. The white spot is rather irregular, and the
      maturation period is longer than normal. Transfers of cytoplasm from nc mature
      oocytes into normal stage VI oocytes resulted in abnormal maturation of the
      normal oocytes. Reciprocal transfers (cytoplasm from normal mature oocytes into
      nc stage VI oocytes) induce the formation of spindles, usually cytoplasmic; this
      indicates that the deficiency can be partly rescued. Following fertilization, the
      nc eggs show neither contraction nor rotation; polyspermy is present in the
      majority of cases. Even in the same egg, simultaneous spindles and nuclei can be
      observed, revealing a disturbance in the spatial localization of regulators of
      the cell cycle. Cytokinesis never occurs. Polyspermy results from the absence of
      cortical reaction following sperm entry. However, when mature nc oocytes are
      treated with PMA, they show cortical granule exocytosis and the formation of an
      altered vitelline envelope. The different factors possibly involved in these
      anomalies are discussed in relation to cytoarchitectural disorganization of the
      cell and abnormal cell cycle regulation.

PMID- 8158103
TI  - Hepatitis B virus C gene heterogeneity in a familial cluster of anti-HBc negative
      chronic carriers.
AB  - We studied a familial cluster of adult HBV chronic carriers characterized by
      serological markers of active viral replication, normal or slightly elevated ALT
      levels and, in four out of five cases, absence of anti-HBc reactivity. The
      nucleotide sequence of the pre-C/C region of HBV was analyzed in three patients,
      showing the presence of wild-type HBV sequences accompanied by different deleted
      molecules. Some of the variant genomes were able to encode proteins retaining
      HBcAg and/or HBeAg reactivity, whereas others contained deletions leading to the
      synthesis of truncated proteins that could not be immunoprecipitated by anti-HBc
      or anti-HBe mono- and polyclonal antibodies. Defective molecules encoded by the
      variant C gene sequences might play a role in the determination of the clinical
      profile observed in the analyzed patients.

PMID- 8158104
TI  - Thirteen current anti-HIV-1/HIV-2 enzyme immunoassays: how accurate are they?
AB  - The sensitivity and specificity of 13 current anti-HIV-1/HIV-2 screening enzyme
      immunoassays (EIA) for the detection of anti-HIV in human serum or plasma were
      investigated by testing against a panel of 454 well-characterised serum or plasma
      specimens. The panel included specimens confirmed to contain anti-HIV-1 (n = 96),
      anti-HIV-2 (n = 26), or low levels of anti-HIV (n = 44) as well as specimens
      collected during HIV-1 seroconversion (n = 73). Specimens from unselected blood
      donors (n = 80) and samples from patients with a range of pathological conditions
      (n = 135) were also included. Observed sensitivities ranged from 96.9% (Biochrom,
      UBI, and Vironostika) to 100% (Biotest, Cambridge Biotech, IAF Biochem, Ortho,
      and Vidas). For the seroconversion specimens, Biotest, Cambridge Biotech, Ortho,
      and Vidas were most sensitive. Observed specificities ranged from 89.9% (UBI) to
      100% (Biochrom and Ortho). One assay (Ortho HIV 1+2 EIA) achieved maximum
      sensitivity and specificity, and was one of four assays to detect anti-HIV-1
      early in seroconversion. The accuracy of several of the other EIAs was also quite
      adequate, so additional factors such as convenience and cost can be considered
      when choosing an assay from the group evaluated.

PMID- 8158105
TI  - Primary human herpesvirus-6 infection is frequently overlooked as a cause of
      febrile fits in young children.
AB  - Sera from 248 children aged 30-179 weeks were tested retrospectively for human
      herpesvirus-6 (HHV-6) IgG antibody avidity. Twenty-five children presented with
      febrile fits, in one case with a rash, exanthem subitum resulting from primary
      HHV-6 infection was diagnosed at the time, but in the others HHV-6 was not
      considered in the differential diagnosis even though two patients had a rash. In
      fact, five of the 25 patients experienced primary infection as shown by low
      avidity HHV-6 antibody. Although nine other of these patients were seronegative
      in the acute phase of the illness, and unfortunately convalescent sera were not
      available to confirm primary HHV-6 infection, seronegativity was clearly a risk
      factor for febrile fits (P = 0.03, odds ratio 3.14 for all children; P = 0.002,
      odds ratio 7.20 for children aged 70-179 weeks), and primary HHV-6 infection was
      a very likely diagnosis. The remaining 11 children had high avidity antibody, so
      HHV-6 was excluded as a cause of their febrile fits. HHV-6 may frequently be a
      cause of febrile fits, often without the typical rash of exanthem subitum, and
      this diagnosis is often overlooked by clinicians.

PMID- 8158106
TI  - Case report: role of hepatitis E virus in the etiology of community-acquired non
      A, non-B hepatitis in Greece.
AB  - The aim of this study was to determine the frequency of hepatitis E virus (HEV)
      infection in a population of Greek adults with community-acquired (sporadic) non
      A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus
      (anti-HCV). All patients admitted to the Liver Unit of Western Attica General
      Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis
      between February, 1986, and May, 1990, were enrolled in follow up studies (n =
      66). Nineteen patients with HCV infection and 11 patients with acute non-A, non
      B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera
      were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking
      assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be
      positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from
      this patient showed evidence of anti-HEV seroconversion at the fourth week after
      the onset of hepatitis. The patient had not travelled abroad or within Greece or
      had not had apparent contact with people from foreign countries for the previous
      3 months. These data show that HEV infection is not a major cause of community
      acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV
      hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive
      seroprevalence studies are needed for an accurate estimation of the extent of HEV
      infection in the southeastern European countries.

PMID- 8158107
TI  - Chronic liver disease in Peru: role of viral hepatitis.
AB  - The prevalence of antibodies to hepatitis C virus (anti-HCV) was determined in
      105 patients with biopsy-proven chronic liver disease and 128 comparison patients
      without any evidence of liver pathology living in Lima, Peru. Using a second
      generation EIA screening and supplemental immunoblot assay, anti-HCV was detected
      in four of 13 patients with chronic hepatitis, in 11% of 85 patients with
      cirrhosis, and in none of seven patients with hepatocellular carcinoma. Only two
      (1.6%) comparison patients without liver disease had anti-HCV. Hepatitis B
      surface antigen (HBsAg) was found in 23% of patients with chronic hepatitis, 12%
      of patients with cirrhosis, and three of seven patients with hepatocellular
      carcinoma. There was no evidence of chronic viral hepatitis or alcohol abuse
      (reported by one-third of subjects) in 48% of chronic liver disease patients.
      These preliminary data suggest that among this South American population neither
      hepatitis B nor hepatitis C infection is the predominate cause of chronic liver
      disease and that other infectious or environmental factors may be important.

PMID- 8158108
TI  - Etiological role of hepatitis E virus in sporadic fulminant hepatitis.
AB  - Non-A, non-B hepatitis viruses have been implicated as the etiological agent(s)
      in up to 60% of patients with fulminant hepatitis. These agents are reported to
      induce a higher mortality than other causes of fulminant hepatitis. Hepatitis E
      virus (HEV) and hepatitis C virus (HCV) at present constitute the major
      identifiable non-A, non-B hepatitis agents. Of these, HEV has been established as
      the sole cause of epidemic hepatitis in Afro-Asian countries, and fulminant
      hepatitis has been recorded during such epidemics. However, in sporadic cases,
      the etiological role of HEV in fulminant hepatitis has remained uncertain. The
      role of HCV in acute liver disease and fulminant hepatitis remains unclear. The
      present study was undertaken to investigate the association of HEV and HCV in
      patients with fulminant hepatitis by direct detection of the viral genome using
      reverse transcription-polymerase chain reaction (RT-PCR). Serum samples from 50
      serologically identified non-A, non-B fulminant hepatitis cases negative for
      cryptic hepatitis B virus (HBV) infection examined via PCR were tested for HEV
      and HCV RNA using RT-PCR. For HEV primers from the nonstructural region (ORF-1)
      were used, and for HCV primers from the highly conserved 5' untranslated regions
      were used. The products were analysed using agarose gel electrophoresis and
      confirmed by hybridisation with radiolabelled internal oligonucleotide probes.
      HEV was detected in 31 (62%) of the 50 fulminant non-A, non-B hepatitis cases. In
      18 (36%) cases, HCV RNA was detected. In 11 (22%) of the HCV cases, the HEV
      genome was also amplified. In 20 (40%) cases, HEV was detected alone.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8158109
TI  - Seroprevalence studies using a recombinant Norwalk virus protein enzyme
      immunoassay.
AB  - A recombinant Norwalk virus (NV) protein enzyme immunoassay was used to study the
      age of acquisition of NV IgG in various populations. In London, England, there
      was little evidence of infection during the first 2 years of life. However, the
      prevalence of NV IgG rose steadily throughout the period that children attend
      school, reaching a peak of 70% in the group aged 11-16 years. High levels of
      maternal antibody were detected in infants aged < 3 months. Comparison of the
      acquisition of antibodies to three strains of human calicivirus in Japanese
      children in northern Japan indicated that although the majority had experienced
      infection with strains Japan and UK1 by the age of 12 years, only 22% possessed
      antibodies to NV. In Australian aborigines NV infection occurs early in life; by
      the age of 6 years over 90% of children were seropositive.

PMID- 8158110
TI  - Presence of hepatitis B and C viral genomes in US blood donors as detected by
      polymerase chain reaction amplification.
AB  - Hepatitis C virus (HCV) represents a major cause of posttransfusion hepatitis
      worldwide. Posttransfusion hepatitis associated with hepatitis B virus (HBV)
      continues to occur. HBsAg-negative donor sera from the Rhode Island Blood Center
      between 1987 and 1988 were screened using more sensitive techniques to assess the
      prevalence of low level HBV infection. Group I consists of 866 healthy blood
      donors without HBV serologic markers, group II consists of 377 donors with ALT
      elevations (> 45 IU/L), group II consists of 148 donors positive for anti-HBc,
      and group IV consists of eight donors positive for both surrogate markers. A
      sensitive monoclonal immunoradiometric assay (M-IRMA) was employed for detection
      of HBsAg-associated epitopes (detection limit of 20 pg/ml) in serum. A subset of
      sera were analyzed for the presence of HBV DNA using the method of anti-HBs
      capture of HBV related virions in serum followed by polymerase chain reaction
      (PCR) amplification. Using these techniques, 0.8% and 1.7% of donors were
      positive for HBsAg and HBV DNA respectively in group I. In contrast, 0.9% and
      9.5% in group II and 0.7% and 18.1% in group III were positive, respectively.
      There were eight donors with both ALT elevation and anti-HBc; and four (50%) of
      these were positive for HBV DNA. In the group with anti-HBc, the majority (80%)
      of donors with HBV DNA had either no or low (signal to noise ratio < 10) anti-HBs
      titer. Using anti-HCV testing and reverse transcription-PCR for detection of HCV
      genomes, we detected evidence of HCV infection in nine of the 49 donors with low
      level HBV DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158111
TI  - Detection of cytomegalovirus mRNA and DNA encoding the immediate early gene in
      peripheral blood leukocytes from immunocompromised patients.
AB  - Detection of cytomegalovirus (CMV) DNA in peripheral blood leukocytes has been
      shown to be a sensitive marker of CMV infection. However, the specificity with
      regard to its clinical significance is less clear, since infections considered to
      be latent may be detected. In this report, the presence of CMV immediate early
      antigen (IEA) DNA and mRNA in peripheral blood leukocytes detected by PCR was
      investigated and related to the appearance of CMV pp65 antigen, CMV serology, and
      clinical status. Thirty-seven consecutive samples were submitted to the
      laboratory from 36 immunocompromised patients, on a routine basis for analysis
      because of a potential risk of CMV infection. To facilitate differentiation
      between DNA and mRNA, primers were chosen in exons 2 and 3 of the immediate early
      gene of CMV. Keratin type I mRNA and the ssu rRNA gene served as internal
      controls. Thirty specimens were CMV antibody positive, of which 11 were also CMV
      IEA DNA positive. Two of seven seronegative samples were CMV IEA DNA positive. No
      relation was found between serology and the presence of CMV IEA DNA as determined
      in 37 samples. Five of 32 samples that could be analyzed were positive for CMV
      IEA mRNA, of which four were also positive in the pp65 antigen detection
      technique. A clear relation was found between the presence of CMV IEA mRNA and
      CMV pp65 antigen in leukocytes and with the clinical findings as well (P < 0.01).
      It is concluded that detection of CMV mRNA may have a role in diagnosis of an
      active clinically relevant CMV infection.

PMID- 8158112
TI  - Cytomegalovirus DNA in arterial walls of patients with atherosclerosis.
AB  - The biological properties of cytomegalovirus (CMV) are consistent with a
      potential role in the pathogenesis of atherosclerosis. The evidence of such a
      role has so far been circumstantial, but CMV nucleic acid is beginning to be
      reported with increasing frequency in the arterial wall. Arterial specimens from
      135 patients who underwent vascular surgery for symptomatic atherosclerotic
      vessel disease were analyzed by PCR for the presence of CMV nucleic acid. Samples
      were studied from the atheromatous plaque area and from uninvolved aortic tissues
      of patients undergoing surgery for vascular disease. One primer pair (LA) was
      used for detection of a late gene, and two other primer pairs (E1 and E2) were
      used for the immediate early gene region. Serum antibody to CMV was measured by
      radioimmunoassay. With the late gene primer, CMV nucleic acid was found in 76% of
      the tissue specimens tested, whereas the E2 gene primer complementary to the
      transforming mtr2 region was reactive in 90% of the arterial samples. There was
      no significant difference in the prevalence of CMV DNA in atherosclerotic plaque
      tissue and in uninvolved aortic tissue from the patients. A second early gene
      primer was not reactive with the tissue specimens, although it gave positive
      results with the positive control of infectious virus. Serum antibody to CMV was
      detected in 86% of the patients in whose tissue CMV DNA was demonstrated. CMV DNA
      was detected in a high proportion of atherosclerotic plaque tissues as well as in
      uninvolved aortic tissue of surgical patients, suggesting that latent CMV
      infection of the arterial wall may be a common occurrence in patients with
      atherosclerosis.

PMID- 8158113
TI  - Cytomegalovirus infection and allospecific cytotoxic activity of graft
      infiltrating cells after heart transplantation.
AB  - We have investigated whether cytomegalovirus (CMV) infection has an effect on
      donor directed cytotoxicity of graft-infiltrating cells in human heart
      transplants. Our study group consisted of 89 heart transplant recipients. Thirty
      eight (43%) showed signs of CMV infection; in 28 of them, cytolytic activity of
      biopsy derived cultures could be tested during the infection. Eight patients had
      a primary and 20 a secondary infection. We found that during CMV infection, both
      primary and secondary, a significantly higher proportion of the biopsy-derived
      cultures showed cytotoxicity against donor HLA antigens (chi 2 test; P < 0.01 in
      comparison with 51 patients without infection). This was most evident in patients
      with both infection and acute rejection episodes when compared to patients with
      only one of these complications. This suggests that one process amplifies the
      other with regard to the up-regulation of alloreactivity within the transplanted
      heart. In secondary infections, only an increase of donor class I-directed
      cytotoxicity was found, while in primary infections cytotoxicity against donor
      class I and II antigens was increased (P < 0.005 vs. secondary infection).

PMID- 8158114
TI  - Failure to detect genomic viral sequences in pancreatic tissues from two children
      with acute-onset diabetes mellitus.
AB  - Two cases of fatal, acute-onset, insulin-dependent diabetes mellitus (IDDM) in
      children were diagnosed. Epidemiologic and serologic studies, as well as
      histologic analysis of pancreatic tissue in fatal viral infections, support the
      contention that a viral infection could cause beta cell destruction, leading to
      IDDM. The presence of nucleic acid sequences from viral agents considered to be
      potentially diabetogenic, specifically, cytomegalovirus and mumps, rubella, and
      coxsackie viruses, were investigated in the pancreatic tissues by reverse
      transcription followed by polymerase chain reaction (RT-PCR) and Southern blot
      hybridization. Total pancreatic RNAs extracted from five children who died from
      nondiabetic causes were included as controls. Viral genetic information from any
      of these four viral agents was not found. This result indicates that the acute
      IDDM in these cases was not due to a direct infection of pancreatic beta cells by
      any of the viral agents studied.

PMID- 8158115
TI  - Hepatitis B virus infection in schistosomiasis mansoni.
AB  - Schistosomiasis and hepatitis B virus (HBV) infection are very common in Brazil
      but the interrelationships between the two infections are poorly understood. We
      have undertaken a detailed serological study of the prevalence of HBV markers in
      189 Brazilian patients with chronic schistosomiasis mansoni, 46 with
      hepatointestinal (HIS) and 143 with hepatosplenic (HSS) schistosomiasis, 12 of
      the latter having decompensated liver disease (HSSD), and in 50 control patients.
      Sera were tested for HBsAg, anti-e, anti-HBc, anti-HBs and HBV-DNA. Eighty-three
      (44%) of the 189 schistosoma patients had at least one marker of HBV infection,
      18 of whom (10%) were seropositive for HBsAg. All the controls were HBsAg
      negative, but ten (20%) had anti-HBc and anti-HBs. There was no significant
      difference in the frequency of these markers between HIS (14/46, 30.4%), HSSC
      (43/131, 34.5%), and the controls. Among the HBsAg-positive patients, one had HIS
      (HBV-DNA negative), seven had HSSC (one HBV-DNA positive) and ten had HSSD (six
      HBV-DNA positive), a significant association of HBV carriage with HSSD (P <<
      0.001). Mean (+/- SD) ALT values were significantly (P < 0.001) higher in HBsAg
      positive HSSD patients (70.7 +/- 18 IU/liter) than in those with HSSC (29.5 +/-
      15 IU/liter). Liver biopsies were performed in 12 HBsAg-positive patients (one
      with HIS, three with HSSC, and eight with HSSD) and in 50 HBsAg-negative HSSC
      patients. Seven of the eight HSSD patients had chronic active hepatitis with
      cirrhosis, and one had inactive cirrhosis. All three patients with HSSC and the
      one with HIS had chronic persistent hepatitis, with periportal fibrosis in
      three.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158116
TI  - Simultaneous amplification and detection of specific hepatitis B virus and
      hepatitis C virus genomic sequences in serum samples.
AB  - A sensitive and specific two-stage polymerase chain reaction (PCR) technique was
      developed for the simultaneous amplification and detection of specific genomic
      sequences of hepatitis B virus (HBV) and hepatitis C virus (HCV) in serum
      samples. Initially, HCV-RNA was reverse transcribed to cDNA. This cDNA and DNA
      from HBV were then co-amplified using primer pairs derived from conserved regions
      of HBV and HCV nucleotide sequences. The specificity of PCR products was
      confirmed by liquid hybridization analysis using 32P end-labeled oligomer probes
      specific for the target HBV and HCV nucleotide sequences. Independent human serum
      samples, positive and negative by PCR for both HBV-DNA and HCV-RNA, were used as
      controls. We tested sera from nine donors, of which seven were reactive for
      HBsAg, anti-HBc, and anti-HCV (multiantigen test), one of whom was reactive for
      anti-HCV and anti-HBc, and one of whom was reactive for HBsAg and anti-HBc. The
      assay detected HBV- and HCV-specific genomic sequences in eight of eight sera
      reactive for both HBV and HCV serological markers and also in the serum that was
      reactive for HBV markers only.

PMID- 8158117
TI  - Choline acetyltransferase: celebrating its fiftieth year.
AB  - It is well known that the regulation of choline acetyltransferase (ChAT) activity
      under physiological and pathological conditions is important for the development
      and neuronal activities of cholinergic systems involved in many fundamental brain
      functions. This review focuses on recent progress in understanding the regulation
      of ChAT at the levels of both the protein and the mRNA. A deficiency in ChAT
      activity has been reported for neurodegenerative conditions such as Alzheimer's
      disease, amyotrophic lateral sclerosis, and schizophrenia. Although a major
      feature of ChAT regulation is likely to involve the spatial and temporal control
      of transcription, regulation of expression can also be at the level of RNA
      processing, transport/translocation, turnover, or translation. In addition, there
      is increasing evidence that ChAT might be regulated at the posttranslational
      level by compartmentation and/or covalent modification, i.e., phosphorylation, as
      well as noncovalent modification (protein-protein interaction, etc.). Synaptic
      activity and the state of neuronal transmission may also involve the regulation
      of ChAT at different levels via both positive and negative feedback loops, as was
      demonstrated in the characterization of two ChAT mutant Drosophila strains.
      Clearly, identification of cholinergic-specific elements and the characterization
      of the trans-acting factors that bind to them represent an important area of
      future research. Equally important is research on the mechanisms governing ChAT
      as an enzymatic entity. The future should be an exciting time during which we
      look forward to the elucidation of the cholinergic signal and its regulation as
      well as the determination of the three-dimensional structure of the enzyme.

PMID- 8158118
TI  - Structural studies on D2 dopamine receptors: mutation of a histidine residue
      specifically affects the binding of a subgroup of substituted benzamide drugs.
AB  - A histidine residue (His394) that is likely to be located in the ligand-binding
      region of the D2 dopamine receptor has been mutated to a leucine (Leu394), and
      the properties of the mutant receptor have been determined. For a range of
      antagonists the mutation has only a minor effect on the affinity of the receptor
      for the antagonist. The mutation does, however, elicit a structurally specific
      effect on the affinity with which certain members of the substituted benzamide
      class of antagonist bind to the receptor. Some of these drugs, e.g., sulpiride,
      sultopride, and tiapride, bind with reduced affinity to the mutated receptor,
      whereas others, e.g., clebopride and metoclopramide, bind with increased
      affinity. However, the Na+/H+ sensitivity of the binding of sulpiride to the
      receptor is not reduced by the mutation. These findings have been interpreted in
      terms of the productive or unfavourable interaction of the His394 residue with
      these compounds.

PMID- 8158119
TI  - Overexpressed monomeric human acetylcholinesterase induces subtle ultrastructural
      modifications in developing neuromuscular junctions of Xenopus laevis embryos.
AB  - Formation of a functional neuromuscular junction (NMJ) involves the biosynthesis
      and transport of numerous muscle-specific proteins, among them the acetylcholine
      hydrolyzing enzyme acetylcholinesterase (AChE). To study the mechanisms
      underlying this process, we have expressed DNA encoding human AChE downstream of
      the cytomegalovirus promoter in oocytes and developing embryos of Xenopus laevis.
      Recombinant human AChE (rHAChE) produced in Xenopus was biochemically and
      immunochemically indistinguishable from native human AChE but clearly
      distinguished from the endogenous frog enzyme. In microinjected embryos, high
      levels of catalytically active rHAChE induced a transient state of over
      expression that persisted for at least 4 days postfertilization. rHAChE appeared
      exclusively as nonassembled monomers in embryos at times when endogenous Xenopus
      AChE displayed complex oligomeric assembly. Nonetheless, cell-associated rHAChE
      accumulated in myotomes of 2- and 3-day-old embryos within the same subcellular
      compartments as native Xenopus AChE. NMJs from 3-day-old DNA-injected embryos
      displayed fourfold or greater overexpression of AChE, a 30% increase in
      postsynaptic membrane length, and increased folding of the postsynaptic membrane.
      These findings indicate that an evolutionarily conserved property directs the
      intracellular trafficking and synaptic targeting of AChE in muscle and support a
      role for AChE in vertebrate synaptogenesis.

PMID- 8158120
TI  - The pyruvate dehydrogenase complex: cloning of the rat somatic E1 alpha subunit
      and its coordinate expression with the mRNAs for the E1 beta, E2, and E3
      catalytic subunits in developing rat brain.
AB  - We report the isolation of cDNA clones encoding the somatic form of the E1 alpha
      subunit of the pyruvate dehydrogenase complex of rat. The deduced amino acid
      sequence has 99.5, 98, and 97% identity, respectively, with the orthologous
      proteins of mouse, human, and pig and 98.5% identity with a rat E1 alpha sequence
      reported previously. The cDNAs isolated in this and earlier studies predict
      different E1 alpha subunit mRNA sizes and amino acid sequences. These differences
      have been investigated by PCR, northern blot hybridization, and RNase protection.
      We have used our E1 alpha cDNA, in conjunction with cDNA probes to the E1 beta,
      E2, and E3 catalytic subunits of rat pyruvate dehydrogenase complex and also to
      rat citrate synthase, to perform RNase protection assays of developing rat whole
      brain RNA. The results show a 2.5-fold increase in the concentration of each of
      the subunit mRNAs and a 1.2-fold increase in citrate synthase mRNA from late
      foetal stage to 5 days post partum. Thereafter, the mRNA levels remained
      constant. These data indicate that the respective six- and threefold increases in
      the amounts of pyruvate dehydrogenase complex and citrate synthase found to occur
      in rat brain between birth and adulthood are mediated principally by
      translational and/or posttranslational mechanisms.

PMID- 8158121
TI  - Insulin-like growth factor-I-enhanced secretion is abolished in protein kinase C
      deficient chromaffin cells.
AB  - Previous studies have demonstrated that bovine chromaffin cells cultured in
      medium with 10 nM insulin-like growth factor-I (IGF-I) secrete about twofold more
      catecholamine when exposed to secretory stimuli than do cells cultured without
      IGF-I. The purpose of this study was to determine whether protein kinase C (PKC)
      is involved in the effect of IGF-I on secretion from these cells. PKC was down
      regulated in the cells by 16-18 h of treatment with beta-phorbol didecanoate
      (beta-PDD; 100 nM). Such treatment had no effect on high-K(+)-stimulated
      secretion from cells cultured without IGF-I; however, secretion from cells
      cultured with IGF-I was reduced to a level comparable to that in cells cultured
      without the peptide. The inactive isomer, alpha-PDD (100 nM), had no effect on
      secretion from untreated or IGF-I-treated chromaffin cells. The effect of beta
      PDD was time and concentration dependent, with 100 nM beta-PDD producing a
      maximal effect in 8-10 h. In situ PKC activity measured in permeabilized cells
      treated with PMA (300 nM) was decreased by approximately 40% by 10 h and was
      reduced to almost basal levels by 18 h. Immunoblotting experiments demonstrated
      that both alpha- and epsilon-PKC were lost from the cells with time courses
      similar to that seen in the in situ PKC assay. Overnight treatment with the PKC
      inhibitor H7 (100 microM) prevented the enhanced secretion normally seen in IGF-I
      treated cells, whereas HA1004 had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158122
TI  - Activation of nuclear factor kappa B in human neuroblastoma cell lines.
AB  - The nuclear factor kappa B (NF-kappa B) is a eukaryotic transcription factor. In
      B cells and macrophages it is constitutively present in cell nuclei, whereas in
      many other cell types, NF-kappa B translocates from cytosol to nucleus as a
      result of transduction by tumor necrosis factor alpha (TNF alpha), phorbol ester,
      and other polyclonal signals. Using neuroblastoma cell lines as models, we have
      shown that in neural cells NF-kappa B was present in the cytosol and translocated
      into nuclei as a result of TNF alpha treatment. The TNF alpha-activated NF-kappa
      B was transcriptionally functional. NF-kappa B activation by TNF alpha was not
      correlated with cell differentiation or proliferation. However, reagents such as
      nerve growth factor (NGF) and the phorbol ester phorbol 12-myristate 13-acetate
      (PMA), which induce phenotypical differentiation of the SH-SY5Y neuroblastoma
      cell line, activated NF-kappa B, but only in that particular cell line. In a NGF
      responsive rat pheochromocytoma cell line, PC12, PMA activated NF-kappa B,
      whereas NGF did not. In other neuroblastoma cell lines, such as SK-N-Be(2), the
      lack of PMA induction of differentiation was correlated with the lack of NF-kappa
      B activation. We found, moreover, that in SK-N-Be(2) cells protein kinase C (PKC)
      enzymatic activity was much lower compared with that in a control cell line and
      that the low PKC enzymatic activity was due to low PKC protein expression. NF
      kappa B was not activated by retinoic acid, which induced morphological
      differentiation of all the neuroblastoma cell lines used in the present study.
      Thus, NF-kappa B activation was not required for neuroblastoma cell
      differentiation. Furthermore, the results obtained with TNF alpha proved that NF
      kappa B activation was not sufficient for induction of neuroblastoma
      differentiation.

PMID- 8158123
TI  - In vivo evidence that nonneuronal beta-adrenoceptors as well as dopamine
      receptors contribute to cyclic AMP efflux in rat striatum.
AB  - We applied in vivo microdialysis to assess the effects of dopaminergic and beta
      adrenergic receptor stimulation on cyclic AMP efflux in rat striatum under
      chloral hydrate anesthesia. Dopamine (up to 1 mM) infused for 20 min through the
      probe did not increase cyclic AMP, whereas both the selective dopamine D1 agonist
      SKF 38393 and D2 antagonist sulpiride produced modest increases. It is
      interesting that the beta-adrenoceptor agonist isoproterenol produced a marked
      increase (204.7% of basal level at 1 mM) which was antagonized by the beta
      adrenoceptor antagonist propranolol. Pretreatment with a glial selective
      metabolic inhibitor, fluorocitrate (1 mM), by a 5-h infusion through the probe
      attenuated basal cyclic AMP efflux by 30.3% and significantly blocked the
      response to isoproterenol. By contrast, striatal injection of a neurotoxin,
      kainic acid (2.5 micrograms), 2 days before the dialysis experiment did not
      affect basal cyclic AMP or the response to isoproterenol, but blocked the
      response to SKF 38393. These data demonstrate the beta-adrenoceptors as well as
      dopamine receptors contribute to cyclic AMP efflux in rat striatum in vivo. They
      also suggest that basal and beta-adrenoceptor-stimulated cyclic AMP efflux are
      substantially dependent on intact glial cells.

PMID- 8158124
TI  - Calcium dependency and tetrodotoxin sensitivity of neostriatal dopamine release
      in 5-day-old and adult rats as measured by in vivo microdialysis.
AB  - The calcium dependency and tetrodotoxin sensitivity of extracellular dopamine
      levels were assessed by microdialysis in the neostriatum of 5-day-old rat pups
      and were compared with those obtained in adult rats. The removal of calcium from
      the dialysate reduced spontaneous levels of extracellular dopamine to 20% of
      normal in the 5-day-old pups and to 10% of normal in the adults. Calcium-free
      dialysate also decreased potassium-evoked dopamine release to approximately 20%
      of baseline in both ages. Furthermore, the addition of tetrodotoxin to the
      dialysate decreased spontaneous levels of extracellular dopamine to 10% of
      baseline in both ages. The effects of calcium removal and the addition of
      tetrodotoxin on extracellular levels of the dopamine metabolite 3,4
      dihydroxyphenylacetic acid were less pronounced. The results of this study
      demonstrate that extracellular levels of dopamine sampled by microdialysis in
      rats as young as 5 days of age are both calcium dependent and tetrodotoxin
      sensitive; thus, they are derived from neuronal activity and not from injury
      caused by acute implantation of the probe. Other age-related differences support
      the hypothesis that dopamine release and turnover is greater in immature rats and
      may represent a form of compensation for incomplete dopamine nerve terminal
      ingrowth.

PMID- 8158125
TI  - Estrogen regulation of dopamine release in the nucleus accumbens: genomic- and
      nongenomic-mediated effects.
AB  - The ability of estrogen to modulate mesolimbic dopamine (DA) was examined using
      in vivo voltammetry. Estrogen priming (5 micrograms, 48 h) of ovariectomized
      (ovx) female rats resulted in a slight decrease in K(+)-stimulated DA release
      measured in the nucleus accumbens: this decrease was accompanied by a significant
      increase in both DA reuptake and DA clearance times. Following estrogen priming
      nomifensine, a potent inhibitor of the DA uptake carrier, was still able to
      potentiate K(+)-stimulated DA release and alter the time course of DA
      availability, but the response was attenuated compared with ovx controls. Direct
      infusion of 17 beta-estradiol hemisuccinate (17 beta-E, 20-50 pg) into the
      nucleus accumbens resulted in a biphasic potentiation of K(+)-stimulated release.
      An initial increase in release was observed 2 min after 17 beta-E infusion; this
      increase, although reduced by 15 min, was still significantly higher than control
      values. A subsequent potentiation was observed 60 min after the initial 17 beta-E
      infusion; this response remained for at least an additional 60 min. Nomifensine
      did not significantly alter K(+)-stimulated DA release following 17 beta-E
      infusion, but was still able to potentiate the total time DA was available
      extracellularly. These data suggest that the mesolimbic A10 DA neurons that
      terminate in the nucleus accumbens can be modulated in vivo by estrogen and that
      this modulation may be mediated by both genomic (long term) and nongenomic (short
      term) mechanisms.

PMID- 8158126
TI  - Free radicals enhance basal release of D-[3H]aspartate from cerebral cortical
      synaptosomes.
AB  - Excessive generation of free radicals has been implicated in several pathological
      conditions. We demonstrated previously that peroxide-generated free radicals
      decrease calcium-dependent high K(+)-evoked L[3H]-glutamate release from
      synaptosomes while increasing calcium-independent basal release. The present
      study evaluates the nonvesicular release of excitatory amino acid
      neurotransmitters, using D-[3H]aspartate as an exogenous label of the cytoplasmic
      pool of L-glutamate and L-aspartate. Isolated presynaptic nerve terminals from
      the guinea pig cerebral cortex were used to examine the actions and interactions
      of peroxide, iron, and desferrioxamine. Pretreatment with peroxide, iron alone,
      or peroxide with iron significantly increased the calcium-independent basal
      release of D-[3H]aspartate. Pretreatment with desferrioxamine had little effect
      on its own but significantly limited the enhancement by peroxide. High K(+)
      evoked release in the presence of Ca2+ was enhanced by peroxide but not by iron.
      These data suggest that peroxide increases nonvesicular basal release of
      excitatory amino acids through Fenton-generated hydroxyl radicals. This release
      could cause accumulation of extracellular excitatory amino acids and contribute
      to the excitotoxicity associated with some pathologies.

PMID- 8158127
TI  - Differential requirements of sodium for coupling of cannabinoid receptors to
      adenylyl cyclase in rat brain membranes.
AB  - Sodium is generally required for optimal inhibition of adenylyl cyclase by Gi/o
      coupled receptors. Cannabinoids bind to specific receptors that act like other
      members of the Gi/o-coupled receptor superfamily to inhibit adenylyl cyclase.
      However, assay of cannabinoid inhibition of adenylyl cyclase in rat cerebellar
      membranes revealed that concentrations of NaCl ranging from 0 to 150 mM had no
      effect on agonist inhibition. This lack of effect of sodium was not unique to
      cannabinoid receptors, because the same results were observed using baclofen as
      an agonist for GABAB receptors in cerebellar membranes. The lack of sodium
      dependence was region-specific, because assay of cannabinoid and opioid
      inhibition of adenylyl cyclase in striatum revealed an expected sodium
      dependence, with 50 mM NaCl providing maximal inhibition levels by both sets of
      agonists. This difference in sodium requirements between these two regions was
      maintained at the G protein level, because agonist-stimulated low Km GTPase
      activity was maximal at 50 mM NaCl in striatal membranes, but was maximal in the
      absence of NaCl in cerebellar membranes. Assay of [3H]WIN 55212-2 binding in
      cerebellar membranes revealed that the binding of this labeled agonist was
      sensitive to sodium and guanine nucleotides like other Gi/o-coupled receptors,
      because both NaCl and the nonhydrolyzable GTP analogue Gpp(NH)p significantly
      inhibited binding. These results suggest that differences in receptor-G protein
      coupling exist for cannabinoid receptors between these two brain regions.

PMID- 8158128
TI  - beta-Lumicolchicine interacts with the benzodiazepine binding site to potentiate
      GABAA receptor-mediated currents.
AB  - An analogue of colchicine, beta-lumicolchicine, does not bind tubulin or disrupt
      microtubules. However, this compound is not pharmacologically completely
      inactive. beta-Lumicolchicine was found to competitively inhibit
      [3H]flunitrazepam binding and to enhance muscimol-stimulated 36Cl- uptake in
      mouse cerebral cortical microsacs. It also markedly potentiated GABA responses in
      Xenopus oocytes expressing human alpha 1 beta 2 gamma 2S, but not alpha 1 beta 2,
      GABAA receptor subunits; this potentiation was reversed by the benzodiazepine
      receptor antagonist flumazenil. These results strongly suggest a direct effect of
      beta-lumicolchicine on the GABAA receptor/chloride channel complex and caution
      that it possesses pharmacological effects, despite its inability to disrupt
      microtubules. Furthermore, beta-lumicolchicine is structurally unrelated to
      benzodiazepines or quinolines and may provide a novel approach to the synthesis
      of ligands for this receptor.

PMID- 8158129
TI  - Sequestration of muscarinic cholinergic receptors in permeabilized neuroblastoma
      cells.
AB  - The feasibility of using a permeabilized preparation of human SH-SY-5Y
      neuroblastoma cells for studies of muscarinic acetylcholine receptor (mAChR)
      sequestration has been evaluated. Exposure of cells permeabilized with digitonin,
      streptolysin-O, or the alpha-toxin from Staphylococcus aureus to oxotremorine-M
      (Oxo-M) for 30 min resulted in a 25-30% reduction in the number of cell surface
      mAChRs, as monitored by the loss of N[3H]methylscopolamine ([3H]NMS) binding
      sites. The corresponding value for intact cells was 40%. For cells permeabilized
      with 20 microM digitonin, the Oxo-M-mediated reduction in [3H]NMS binding was
      time (t1/2 approximately 5 min) and concentration (EC50 approximately 10 microM)
      dependent and was agonist specific (Oxo-M > bethanechol = arecoline =
      pilocarpine). In contrast, no reduction in total mAChR number, as monitored by
      the binding of [3H]quinuclidinyl benzilate, occurred following Oxo-M treatment.
      The loss of [3H]NMS sites observed in the presence of Oxo-M was unaffected by
      omission of either ATP or Ca2+, both of which are required for stimulated
      phosphoinositide hydrolysis, but could be inhibited by the inclusion of guanosine
      5'-O-(2-thiodiphosphate). mAChRs sequestered in response to Oxo-M addition were
      unmasked when the cells were permeabilized in the presence of higher
      concentrations of digitonin (80 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158130
TI  - Hippocampal serotonin 5-HT1A receptor enhances acetylcholine release in conscious
      rats.
AB  - We investigated changes in the extracellular levels of acetylcholine (ACh)
      following local application of serotonergic agents to the dorsal hippocampus of
      freely moving rats by means of perfusion using a microdialysis technique.
      Perfusion of serotonin (5-HT; 10 microM, for 30 min at a rate of 3
      microliters/min), dissolved in Ringer's solution containing 10 microM eserine,
      showed no marked effect on the extracellular levels of ACh. 8-Hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT; 20 microM), a 5-HT1A agonist, increased ACh
      levels, whereas 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2
      a]quinoxaline (CGS-12066B; 100 microM), a 5-HT1B agonist, decreased it.
      Clomipramine (2 microM), an uptake inhibitor of 5-HT, had no effect on ACh
      levels. Following perfusion of 1-(2-methoxyphenyl)-4-[4-(2
      phthalimido)butyl]piperazine (NAN-190; 10 microM), which is a selective 5-HT1A
      antagonist, the effect of 8-OH-DPAT was totally abolished, whereas CGS-12066B
      decreased extracellular ACh levels. 5-HT, as well as clomipramine, had a
      decreasing effect on ACh levels after pretreatment with NAN-190. These results
      indicate that the 5-HT1A receptor, which exists in the dorsal hippocampus,
      enhances the spontaneous ACh release, and that the mechanism of serotonergic
      modulation of ACh release partly depends on both the stimulatory control via the
      5-HT1A receptor and the suppressive one via the 5-HT1B receptor in the dorsal
      hippocampus of rats.

PMID- 8158131
TI  - Characterization of low pH-induced catecholamine secretion in the rat adrenal
      medulla.
AB  - Catecholamine (CA) secretion was evoked when the isolated rat adrenal gland was
      perfused with HEPES-buffered Krebs solution acidified by the addition of HCl or
      by gassing with 95% O2/5% CO2. The secretion was detectable at pH 7.0 and
      increased with decreasing pH until at approximately 6.4. The low pH-induced CA
      secretion consisted of two phases, an initial transient response followed by a
      sustained phase. An intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8
      (N,N-diethylamino)octyl ester, selectively inhibited the initial phase of
      secretion. Both of the responses were resistant to nifedipine, a blocker of
      voltage-gated Ca2+ channel, but were completely inhibited in Ca(2+)-free (1 mM
      EGTA containing) solution. Adrenaline was an exclusive component in CAs released
      by low pH. The time course and extent of intracellular acidification caused
      either by low pH in the external medium or by the offset of a transitory NH4Cl
      application had no correlation with those of the secretory responses in the
      corresponding period. These results suggest that extracellular acidification
      preferentially activates adrenaline secretive cells to evoke CA secretion and
      that this low pH-induced CA secretion may be mediated by dihydropyridine
      insensitive Ca2+ influx. Furthermore, the initial transient phase of the low pH
      induced CA secretion might be caused by a Ca2+ release from intracellular stores,
      which is also induced by the Ca2+ influx.

PMID- 8158132
TI  - Serotonin 5-HT1A receptor activation increases cyclic AMP formation in the rat
      hippocampus in vivo.
AB  - In vivo microdialysis was used to examine the efflux of cyclic AMP (cAMP) into
      the extracellular fluid of the ventral hippocampus in the freely moving rat. The
      changes in extracellular cAMP concentration were monitored in response to
      forskolin and the serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT). The basal level of hippocampal extracellular
      cAMP was 2.3 +/- 0.2 pmol/ml (n = 6), after a 3-h postsurgery stabilisation
      period. Perfusion of forskolin (100 microM) through the probe for 30 min
      significantly increased the efflux of cAMP, which returned to baseline levels
      within 90 min. 8-OH-DPAT (0.3 mg/kg s.c.) also significantly increased cAMP
      efflux, whereas a similar volume of saline had no effect. Desensitisation of the
      8-OH-DPAT-induced increase in cAMP efflux was observed following a second
      administration of 8-OH-DPAT after a 4-h interval. Administration of 8-OH-DPAT did
      not alter the efflux of cAMP when forskolin was perfused through the probe.
      Pretreatment with WAY 100135 [N-tert-butyl 3-4-(2-methoxyphenyl)piperazine-1-yl-2
      phenylpropanamide dihydrochloride] (5 mg/kg s.c.), a specific 5-HT1A receptor
      antagonist, prevented the 8-OH-DPAT-induced increase in cAMP efflux. The data
      indicate that the 8-OH-DPAT-induced increase in cAMP efflux in vivo is mediated
      by a 5-HT1A receptor.

PMID- 8158133
TI  - Heterogeneity of cortical and hippocampal 5-HT1A receptors: a reappraisal of
      homogenate binding with 8-[3H]hydroxydipropylaminotetralin.
AB  - The selective serotonin (5-HT) agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT)
      has been extensively used to characterize the physiological, biochemical, and
      behavioral features of the 5-HT1A receptor. A further characterization of this
      receptor subtype was conducted with membrane preparations from rat cerebral
      cortex and hippocampus. The saturation binding isotherms of [3H]8-OH-DPAT (free
      ligand from 200 pM to 160 nM) revealed high-affinity 5-HT1A receptors (KH = 0.7
      0.8 nM) and low-affinity (KL = 22-36 nM) binding sites. The kinetics of [3H]8-OH
      DPAT binding were examined at two ligand concentrations, i.e., 1 and 10 nM, and
      in each case revealed two dissociation rate constants supporting the existence of
      high- and low-affinity binding sites. When the high-affinity sites were labeled
      with a 1 nM concentration of [3H]8-OH-DPAT, the competition curves of agonist and
      antagonist drugs were best fit to a two-site model, indicating the presence of
      two different 5-HT1A binding sites or, alternatively, two affinity states,
      tentatively designated as 5-HT1AHIGH and 5-HT1ALOW. However, the low correlation
      between the affinities of various drugs for these sites indicates the existence
      of different and independent binding sites. To determine whether 5-HT1A sites are
      modulated by 5'-guanylylimidodiphosphate, inhibition experiments with 5-HT were
      performed in the presence or in the absence of 100 microM 5'
      guanylylimidodiphosphate. The binding of 1 nM [3H]8-OH-DPAT to the 5-HT1AHIGH
      site was dramatically (80%) reduced by 5'-guanylylimidodiphosphate; in contrast,
      the low-affinity site, or 5-HT1ALOW, was seemingly insensitive to the guanine
      nucleotide. The findings suggest that the high-affinity 5-HT1AHIGH site
      corresponds to the classic 5-HT1A receptor, whereas the novel 5-HT1ALOW binding
      site, labeled by 1 nM [3H]8-OH-DPAT and having a micromolar affinity for 5-HT,
      may not belong to the G protein family of receptors. To further investigate the
      relationship of 5-HT1A sites and the 5-HT innervation, rats were treated with p
      chlorophenylalanine or with the neurotoxin p-chloroamphetamine. The inhibition of
      5-HT synthesis by p-chlorophenylalanine did not alter either of the two 5-HT1A
      sites, but deafferentation by p-chloroamphetamine caused a loss of the low
      affinity [3H]8-OH-DPAT binding sites, indicating that these novel binding sites
      may be located presynaptically on 5-HT fibers and/or nerve terminals.

PMID- 8158134
TI  - Growth of ectopic dendrites on cortical pyramidal neurons in neuronal storage
      diseases correlates with abnormal accumulation of GM2 ganglioside.
AB  - Ganglioside analysis and quantitative Golgi studies of the cerebral cortex of
      cats with ganglioside and nonganglioside lysosomal storage diseases reveal a
      correlation between the amount of accumulated GM2 ganglioside and the extent of
      ectopic dendrite growth on cortical pyramidal neurons. This correlation was not
      observed with any of the other gangliosides assayed for, including GM1
      ganglioside. These results suggest a specific role for GM2 ganglioside in the
      initiation of ectopic neurites on pyramidal cells in vivo and are consistent with
      the developing hypothesis that different gangliosides have specific roles in
      different cell types dependent upon the receptor or other effector molecules with
      which they may interact.

PMID- 8158135
TI  - Nicotine tolerance in chromaffin cell cultures: acute and chronic exposure to
      smoking-related nicotine doses.
AB  - Nicotine tolerance and dependence are key aspects of tobacco addiction; however,
      the cellular mechanisms underlying these phenomena are poorly understood. Adrenal
      chromaffin cells release catecholamines upon exposure to nicotine and with
      repeated exposure this response exhibits nicotine tolerance. Using bovine adrenal
      chromaffin cells in culture, we have demonstrated acute and chronic nicotine
      tolerance at doses relevant to that in the blood and tissues of smokers (10(-7) M
      to 10(-6) M). Chromaffin cells are preexposed to low doses of nicotine for time
      periods ranging from 10 min to 7 days and then subsequently challenged with a
      maximally stimulating dose of nicotine (10(-5) M) for 10 min, all at 37 degrees
      C. Preexposure to nicotine results in a depression of 45Ca uptake and
      catecholamine release upon subsequent nicotine challenge. Acute tolerance or
      desensitization of nicotine-stimulated catecholamine release begins to occur in
      minutes after preexposure to 10(-6) M nicotine at 37 degrees C. The depression of
      catecholamine release upon preexposure to nicotine is both dose and temperature
      dependent and is not seen with potassium-evoked release. Chronic exposure to 10(
      7) M nicotine for 3 days led to a depression of the secretory response to
      approximately 70% of control responses. There was a trend toward recovery of full
      response by days 5 and 7 of 10(-7) M nicotine preexposure. Nearly complete
      depression of the nicotine-evoked release occurs within the first day of exposure
      to 10(-6) M nicotine and persists for at least a week of nicotine exposure at 37
      degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158136
TI  - Acute and persistent suppression of preproenkephalin mRNA expression in the
      striatum following developmental hypoxic-ischemic injury.
AB  - The striatum is vulnerable to hypoxic-ischemic injury during development. In a
      rodent model of perinatal hypoxia-ischemia, it has been shown that striatal
      neurons are not uniformly vulnerable. Cholinergic neurons and NADPH-diaphorase
      positive neurons are relatively spared. However, it is unknown what classes of
      striatal neurons are relatively sensitive. One of the major classes of striatal
      neurons uses enkephalin as a neurotransmitter. We have studied the effect of
      early hypoxic-ischemic injury on this class of neurons using a quantitative
      solution hybridization assay for preproenkephalin mRNA in conjunction with in
      situ hybridization. Hypoxia-ischemia results in an early (up to 24 h) decrease in
      striatal preproenkephalin mRNA, which is shown by in situ hybridization to occur
      mainly in the dorsal portion of the striatum. By 14 days, whole striatal
      preproenkephalin mRNA and total enkephalin-containing peptide levels are normal.
      However, at 14 days, in situ hybridization reveals that regions of complete
      preproenkephalin mRNA-positive neuron loss remain in the dorsal region. Normal
      whole striatal levels are due to an up-regulation of preproenkephalin mRNA
      expression in the ventrolateral region of the injured striatum. Given the
      important role that the enkephalin-containing striatal efferent projection plays
      in regulating motor function, its relative loss may be important in the chronic
      disturbances of motor control observed in brain injury due to developmental
      hypoxic-ischemic injury.

PMID- 8158137
TI  - Identification of a peripherin dimer: changes during axonal development and
      regeneration of the rat sciatic nerve.
AB  - Western blotting of rat dorsal root ganglion (DRG) and sciatic nerve under
      nonreducing conditions revealed that a peripherin-specific antibody recognized a
      protein species of 116/130 kDa, pI 5.6, in addition to peripherin (56 kDa, pI
      5.6). We showed that this 116/130 kDa protein is a disulfide dimer of peripherin,
      because it gave rise to a single protein band comigrating with peripherin under
      reducing conditions and yielded the same proteolytic pattern as peripherin upon N
      chlorosuccinimide digestion. In addition, the immunological characteristics of
      the resulting peptides were identical to those of peripherin. We investigated the
      changes in peripherin monomer and dimer protein levels during axonal development
      and regeneration. During postnatal development, quantitative analysis of western
      blots of DRG proteins showed a significant increase in peripherin monomer (+52%)
      and dimer (+33%) levels from the day of birth [postnatal day 0 (P0)] to P7. The
      monomer levels remained high until P14 and then decreased so that at P21 and
      later ages, the monomer levels were similar to those observed at birth. In
      contrast, the dimer levels decreased continuously after P7, and in the adult, its
      level represented only 30% of the level at birth. Changes in [35S]methionine
      incorporation into adult DRG proteins were studied during regeneration of
      axotomized sciatic axons. Quantitative analysis of proteins showed a strong
      increase in labeling of both peripherin monomer (+56%) and dimer (+88%) 7 days
      after the crush. These levels, which remained high until 28 days after the
      axotomy, had returned to normal 70 days post axotomy. Our results show that
      peripherin monomer and dimer greatly increase during DRG fiber development and
      regeneration, suggesting that the two forms are involved in the growth of axons.

PMID- 8158138
TI  - Resistance of golden hamster to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine:
      relationship with low levels of regional monoamine oxidase B.
AB  - Effects of acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) were investigated for dopamine (DA) and its
      metabolites, 3,4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic
      acid, in nucleus caudatus putamen (NCP), limbic system, and substantia nigra (SN)
      of golden hamster and BALB/c and C57/BL mice to obtain a clue for the variance of
      MPTP toxicity between the strains and species. Regional differences in the levels
      of monoamine oxidase (MAO) and the in vitro effects of MAO inhibitors were also
      determined and correlated with MPTP neurotoxicity. Concentrations of MPTP in the
      brains of mice and golden hamster at 10 min were comparable. Golden hamster was
      found to be resistant to the administration of MPTP as indicated by a lack of any
      alteration from the normal content of DA in NCP, limbic system, and SN. Both
      strains of mice exhibited > 50% and > 75% depletion of DA (C57/BL and BALB/c,
      respectively). The metabolites-to-DA ratios were decreased and increased in
      golden hamster and mouse strains, respectively, after acute or chronic treatment.
      Whereas the content of total MAO in golden hamster was one-third to one-sixth of
      any nuclei or mitochondria of both strains of mice, the ratio of MAO A to B was
      significantly higher in the former species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158139
TI  - Stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) decreases
      striatal fructose 2,6-bisphosphate in rats.
AB  - The stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) into the
      neostriatum of male rats caused a lesion that resulted in a large dose-dependent
      loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days
      after the treatment. This effect was not protected by systemic administration of
      MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also
      reduced by MPP+ treatment, whereas lactate was increased. Biochemical and
      histological results suggested that MPP+ caused a nonselective cell death,
      followed by a pronounced astroglial response, parallel to fructose 2,6
      bisphosphate recovery. The stereotaxic administration of rotenone showed a
      different time effect on fructose 2,6-bisphosphate cerebral content, with a
      significantly faster recovery. These results indicate that cerebral fructose 2,6
      bisphosphate may be a sensitive metabolite related to brain damage caused by
      potent neurotoxins such as MPP+. On the other hand, they show that MPP+ acts in
      the brain through a quick, strong cytotoxic mechanism, which probably involves
      mechanisms other than mitochondrial chain blockage.

PMID- 8158140
TI  - Ischemia-induced changes in cerebral mitochondrial free fatty acids,
      phospholipids, and respiration in the rat.
AB  - Changes in the free fatty acid pool size and fatty acyl chain composition of
      mitochondrial membrane phospholipids and their relation to disruption of
      mitochondrial function were examined in rat brains after 30 min of cerebral
      ischemia (Pulsinelli-Brierley model) and 60 min of normoxic reoxygenation. During
      ischemia, significant hydrolysis of polyunsaturated molecular species from diacyl
      phosphatidylcholine, particularly fatty acyl 20:4 (arachidonic acid; 20%
      decrease) and 22:6 (docosahexaenoic acid; 15% decrease), was observed. Thirty
      minutes of ischemia caused a 16% loss of 18:2 (linoleic acid) from
      phosphatidylethanolamine. Recirculation for 60 min did not return the
      polyunsaturated fatty acid content of phospholipids to normal. Total content of
      free fatty acids increased during ischemia, particularly 18:2 and 22:6, which
      exhibited the most dramatic rise. The free fatty acid pool size continued to
      increase during 60 min of recirculation. The respiratory control ratio decreased
      significantly during 30 min of ischemia with no apparent recovery following 60
      min of reoxygenation. The degree of free radical-mediated lipid peroxidation in
      mitochondria was significantly increased during ischemia and reperfusion. It was
      concluded that (a) 30 min of cerebral ischemia caused differential degradation in
      each of the phospholipid classes and preferential hydrolysis of the
      polyunsaturated molecular species and (b) 60 min of normoxic reperfusion failed
      to promote reacylation of the mitochondrial phospholipids and restoration of
      normal respiration.

PMID- 8158141
TI  - Effect of the platelet-activating factor antagonist BN 50739 and its diluents on
      mitochondrial respiration and membrane lipids during and following cerebral
      ischemia.
AB  - Recent evidence suggests that platelet-activating factor plays a role in ischemia
      induced neural injury. The Pulsinelli-Brierley four-vessel occlusion model was
      used to study the effect of a synthetic platelet-activating factor antagonist, BN
      50739, and its solvents, either dimethyl sulfoxide or hydroxypropyl-beta
      cyclodextrin, on cerebral ischemia-reperfusion. Rats were subjected to either 30
      min of ischemia or 30 min of ischemia followed by 60 min of recirculation.
      Changes in the brain mitochondrial free fatty acid pool size, fatty acyl
      composition of phospholipids, and respiratory function were monitored. When the
      BN 50739 (2 mg of BN 50739/kg of body weight i.v.) was administered at the onset
      of recirculation, it significantly reversed the ischemia-induced accumulation of
      mitochondrial free fatty acids and loss of polyunsaturated fatty acyl chains from
      phosphatidylcholine and phosphatidylethanolamine while simultaneously improving
      mitochondrial respiration. Dimethyl sulfoxide alone decreased the mitochondrial
      level of malonyldialdehyde and total free fatty acid pool size, but there was no
      improvement in mitochondrial respiration. Hydroxypropyl-beta-cyclodextrin was
      reported to be pharmacologically inactive and capable of dissolving BN 50739.
      However, hydroxypropyl-beta-cyclodextrin alone also caused a significant increase
      in content of cerebral mitochondrial membrane free fatty acids and hydrolysis of
      phosphatidylcholine in normoxic control animals. The overall effect of BN 50739
      on mitochondrial structure and energy metabolism supports the hypothesis that
      platelet-activating factor may play a key role in ischemia-induced cerebral
      injury.

PMID- 8158142
TI  - Cellular and subcellular localization of hexokinase, glutamate dehydrogenase, and
      alanine aminotransferase in the honeybee drone retina.
AB  - Subcellular localization of hexokinase in the honeybee drone retina was examined
      following fractionation of cell homogenate using differential centrifugation.
      Nearly all hexokinase activity was found in the cytosolic fraction, following a
      similar distribution as the cytosolic enzymatic marker, phosphoglycerate kinase.
      The distribution of enzymatic markers of mitochondria (succinate dehydrogenase,
      rotenone-insensitive cytochrome c reductase, and adenylate kinase) indicated that
      the outer mitochondrial membrane was partly damaged, but their distributions were
      different from that of hexokinase. The activity of hexokinase in purified
      suspensions of cells was fivefold higher in glial cells than in photoreceptors.
      This result is consistent with the hypothesis based on quantitative 2
      deoxy[3H]glucose autoradiography that only glial cells phosphorylate significant
      amounts of glucose to glucose-6-phosphate. The activities of alanine
      aminotransferase and to a lesser extent of glutamate dehydrogenase were higher in
      the cytosolic than in the mitochondrial fraction. This important cytosolic
      activity of glutamate dehydrogenase was consistent with the higher activity found
      in mitochondria-poor glial cells. In conclusion, this distribution of enzymes is
      consistent with the model of metabolic interactions between glial and
      photoreceptor cells in the intact bee retina.

PMID- 8158143
TI  - Activities of five different sialyltransferases in fish and rat brains.
AB  - To investigate the role of sialyltransferases in the metabolism of brain
      gangliosides, we examined activities of five different sialyltransferases (GM3-,
      GD3-, GT3-, GD1a-, and GT1a-synthase) using total membrane preparations from
      cichlid fish and Sprague-Dawley rat brains, and analyzed the relationship between
      the enzyme activities and the ganglioside compositions. The patterns of
      sialyltransferase activities in fish and rat brains differed from each other. In
      fish brain, the GM3-synthase activity was lower than GD3-synthase activity,
      whereas the opposite relationship was observed in rat brain. The GT3-synthase
      reaction with fish brain membranes produced radiolabeled GM3, GD3, and a
      ganglioside that was identified as GT3 based on mobility on TLC using two
      different solvent systems. No GT3-synthase activity was detected in rat brain.
      The GD1a- and GT1a-synthase activities in fish brain were higher than those in
      rat brain. Although GT1a was a single radiolabeled ganglioside in fish GT1a
      synthase reaction, this ganglioside could not be detected in rat brain. The
      ratios of GM3-, GD3-, GT3-, GD1a-, and GT1a-synthase activities in fish and rat
      brain were 23:31:4:28:14 and 61:21:0:18:0, respectively. Ganglioside analysis
      showed that fish brain was enriched with c-series gangliosides including GT3 and
      polysialo-species, whereas a- and b-series gangliosides were major components in
      rat brain. These results suggest that the species-specific expression of
      gangliosides in brain tissues may be regulated, at least in part, at the level of
      sialyltransferase activities.

PMID- 8158144
TI  - Glutamine transaminase K and omega-amidase activities in primary cultures of
      astrocytes and neurons and in embryonic chick forebrain: marked induction of
      brain glutamine transaminase K at time of hatching.
AB  - Glutamine transaminase K and omega-amidase activities are present in the chick
      brain and in the brains of adult mice, rats, and humans. However, the activity of
      glutamine transaminase K in adult mouse brain is relatively low. In the chick
      embryo, cerebral glutamine transaminase K activity is low between embryonic days
      5 and 17, but by day 23 (day of hatching) activity rises dramatically (> 15
      fold). Cerebral omega-amidase activity is relatively high at embryonic day 5 but
      lower between days 5 and 17; at embryonic day 23 the activity rises to a maximum.
      Both glutamine transaminase K and omega-amidase are present in cultured chick,
      rat, and mouse astrocytes and neurons. For each species, the activity of
      glutamine transaminase K is higher in the astrocytes than in the neurons. The
      activity of omega-amidase is about the same in the cultured chick astrocytes and
      neurons but significantly higher in rat astrocytes than in rat neurons. The data
      suggest that the rise in brain glutamine transaminase K activity in the chick
      embryo at hatching correlates with maturation of astrocytes. Glutamine
      transaminase K may be involved in glutamine cycling in astrocytes. Glutamine
      transaminase K appears to be a major cysteine S-conjugate beta-lyase of the brain
      and may play a role in the neurotoxicity associated with exposure to
      dichloroacetylene and perhaps to other toxins.

PMID- 8158145
TI  - Comparison of the effect of calpain inhibitors on two extralysosomal proteinases:
      the multicatalytic proteinase complex and m-calpain.
AB  - The potencies of three peptide aldehyde inhibitors of calpain (calpain inhibitors
      1 and 2 and calpeptin) as inhibitors of four catalytic activities of the
      multicatalytic proteinase complex (MPC) were compared with their potencies as
      inhibitors of m-calpain. The chymotrypsinlike activity (cleavage after
      hydrophobic amino acids) and the caseinolytic activity (degradation of beta
      casein) of MPC were strongly inhibited by calpain inhibitors 1 and 2 (IC50 values
      in the low micromolar range). Cleavage by MPC after acidic amino acids
      (peptidylglutamyl-peptide bond hydrolyzing activity) and basic amino acids
      (trypsinlike activity) was inhibited less effectively, declining moderately with
      increasing concentrations of calpain inhibitors 1 and 2. Calpeptin only weakly
      inhibited the four MPC activities, yet was the most potent inhibitor of m
      calpain. These results indicate that caution must be exercised when calpain
      inhibitors 1 and 2 are used to infer calpain function. Calpeptin may be a better
      choice for such studies, although its effect on other cysteine or serine
      proteinases remains to be determined.

PMID- 8158146
TI  - Diurnal variations in cyclic AMP and melatonin content of golden hamster retina.
AB  - The diurnal variations and photic regulation of cyclic AMP and melatonin content
      in golden hamster retina were studied. Both parameters showed significant diurnal
      variations with maximal values at night. Light exposure during the night
      inhibited retinal cyclic AMP and melatonin levels, whereas exposure to darkness
      during the day significantly increased cyclic AMP and melatonin content.
      Incubation with melatonin of retinas excised at different intervals indicated
      that the methoxyindole inhibited cyclic AMP accumulation in a time-dependent
      manner. The inhibitory effect of melatonin at 2400 h and at noon showed a
      threshold concentration of 1 and 10 pM, respectively. At 0400 h melatonin did not
      affect cyclic AMP accumulation. The results indicate a diurnal variability of
      retinal cyclic AMP and melatonin content in hamsters, mainly influenced by a
      photic stimulus. Cyclic AMP could be a putative second messenger for melatonin
      action in golden hamster retina.

PMID- 8158147
TI  - Photoendocrine transduction in cultured chick pineal cells: IV. What do vitamin A
      depletion and retinaldehyde addition do to the effects of light on the melatonin
      rhythm?
AB  - Light has at least two distinguishable effects on the circadian rhythm of
      melatonin output displayed by dispersed chick pineal cells in static culture:
      acute suppression of melatonin output and entrainment (phase shifts) of the
      underlying pacemaker. Previous results indicated that these two effects of light
      are mediated by different mechanistic pathways. The pathways for the acute and
      phase-shifting effects of light either branch from the same, single photopigment
      or differ from the outset, starting from separate photopigments. If a single
      rhodopsin-like photopigment mediates both effects of light, then vitamin A
      depletion and retinoid addition should affect both responses in parallel,
      although not proportionately. We therefore compared the effects of vitamin A
      depletion and retinoid addition on the acute and phase-shifting effects of light
      under several experimental conditions. When chick pineal cells were depleted of
      vitamin A, acute responses to light were markedly reduced. Addition of 11-cis
      retinaldehyde specifically restored (and enhanced) the acute response. When
      allowed to free run in constant red light, depleted cells displayed a rhythm of
      melatonin output with the same period as that of control cells. In contrast to
      the acute effects, phase shifts in response to 2- or 4-h light pulses did not
      differ between depleted and control cells. Addition of retinaldehyde to depleted
      cells did not, by itself, reduce melatonin output or induce phase shifts.
      Retinaldehyde did increase the acute response to 4-h light pulses but not the
      ensuing phase shifts. Responses increased with duration of the light pulse: Both
      the acute effect and the phase shifts induced by 4-h light pulses were
      considerably larger than those induced by 2-h (or 1-h) light pulses. Addition of
      retinaldehyde to depleted cells increased the acute effect of 2-h (or 1-h) light
      pulses to at least that seen with 4-h light pulses but did not increase the size
      of the ensuing phase shifts. These results strongly confirm previous
      dissociations of the mechanistic pathways mediating the acute and phase-shifting
      effects of light on chick pineal cells. They also support a role for rhodopsin
      like photopigment in the acute, but not phase-shifting, response. They favor, but
      do not prove, the conclusion that separate photopigments mediate the acute and
      entraining effects of light.

PMID- 8158148
TI  - Oxidation products arising from the action of monoamine oxidase B on 1-methyl-4
      benzyl-1,2,3,6-tetrahydropyridine, a nonneurotoxic analogue of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine.
AB  - 1-Methyl-4-benzyl-1,2,3,6-tetrahydropyridine (MBzTP), an analogue of the
      neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, despite its rapid
      oxidation by monoamine oxidase B (MAO B), is not neurotoxic. The pyridinium
      expected to arise from the four-electron oxidation of MBzTP inhibits
      mitochondrial respiration and the oxidation of NADH in inner membranes and is
      only moderately less inhibitory than 1-methyl-4-phenylpyridinium. It is also a
      competitive inhibitor of dopamine uptake by the dopamine transporter and hence
      likely to be taken up into neurons, despite its relatively high Ki value (Ki = 21
      microM). Incubation of MBzTP with purified MAO B yields first the
      dihydropyridinium form, then a mixture of the pyridinium form and another
      unidentified product, in proportions that depend on the concentrations of MAO B
      and oxygen. At low MAO B concentration and moderate oxygen concentration,
      nonenzymatic formation of the unidentified product predominates. The lack of
      neurotoxicity of MBzTP appears to be due to the oxidative destruction of the
      dihydropyridine and consequent failure of accumulation of 1-methyl-4
      benzylpyridinium.

PMID- 8158149
TI  - Estimating extracellular concentrations of dopamine and 3,4-dihydroxyphenylacetic
      acid in nucleus accumbens and striatum using microdialysis: relationships between
      in vitro and in vivo recoveries.
AB  - It is common practice in microdialysis studies for probes to be "calibrated" in
      artificial CSF and in vitro recoveries determined for all substances to be
      measured in vivo. Dialysate concentrations of such substances are then
      "corrected" for in vitro recoveries to provide "estimates" of extracellular
      concentrations. At least for dopamine, in vitro and in vivo recoveries are
      significantly different and, therefore, an estimate of extracellular dopamine
      based on correction for in vitro recovery is likely to be erroneous. Generally,
      however, the relative relationships of such estimates among animals are of
      interest rather than the "true" extracellular values. Such relationships would be
      valid to the extent that estimated values are correlated with or predictive of
      true values. Using the "no net flux" procedure, the present study sought to
      determine, for both dopamine and its metabolite 3,4-dihydroxyphenylacetic acid
      (DOPAC), whether in vitro and in vivo recoveries would correlate with each other
      as well as whether respective estimated and true (no net flux) values of these
      substances would correlate with each other. Probes (3 mm; BAS/CMed MF-5393),
      previously calibrated, were lowered into both the nucleus accumbens and striatum
      of freely moving rats the day before sample collection was begun. In vitro and in
      vivo recoveries were not significantly correlated (r = 0.1-0.3), for either
      dopamine or DOPAC. For both dopamine and DOPAC, however, there were significant
      correlations (r = 0.7-0.8) between estimated and true values. Surprisingly, when
      using these commercial probes, absolute dialysate levels for both substances were
      even better correlated (r = 0.9-0.95) with true values.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8158150
TI  - Unusual low proton permeability of liposomes prepared from the endogenous myelin
      lipids.
AB  - In contrast with most other lipid substrates, in this article we show that
      liposomes prepared from the total myelin lipids exhibited a negligible proton
      permeability. Neither the generation of valinomycin-induced potassium diffusion
      potentials as high as -177 mV nor the imposition of large pH gradients (up to
      three units) was able to produce a substantial flux of protons through liposomal
      membranes, as determined by the distribution of [14C]-methylamine, or the changes
      in the fluorescence of the probes 9-aminoacridine, acridine orange, and pyranine.
      The presence of cations (Na+, K+, Ca2+) did not alter this behavior. Voltage
      clamping did not increase the transmembrane delta pH-driven proton permeability.
      However, liposome diameter was found to be critical because small unilamellar
      vesicles displayed a much higher proton permeability than large unilamellar or
      multilamellar vesicles. This abnormally low proton permeability is interpreted by
      virtue of the characteristic biochemical composition of myelin lipid matrix, with
      a high content of cholesterol and sphingolipids and a very low level of free
      fatty acids. These results could be important for elucidating the role of myelin
      in the regulation of pH in the brain. In addition, the myelin lipid extract could
      be useful for reconstituting proteins that participate in the transport of H+
      through the membrane.

PMID- 8158151
TI  - Neuromelanin of the human substantia nigra: a mixed-type melanin.
AB  - Model melanins, synthesized with different cysteinyldopamine/dopamine ratios in
      the incubates, were oxidized with KMnO4 and the resulting compounds were analyzed
      by HPLC. The ratios between a phaeomelanin-derived compound, thiazole-4,5
      dicarboxylic acid (TDCA), and a compound derived from eumelanin, pyrrole-2,3,5
      tricarboxylic acid (PTCA), reflected the composition of the model melanins. The
      neuromelanin of the human substantia nigra was isolated, and the pigment, as well
      as intact brain tissue from human substantia nigra was oxidized with KMnO4 and
      the TDCA/PTCA ratios were determined. Analysis of the isolated neuromelanin
      showed it to contain 2.3% sulfur and 8.1% nitrogen. The sulfur content indicates
      the pigment is a mixed-type melanin, and the TDCA/PTCA ratio indicates that it
      consists of units derived from benzothiazines and from indoles in about equal
      amounts.

PMID- 8158152
TI  - GABAA receptor subtypes expressed in cerebellar granule cells: a developmental
      study.
AB  - The developmental properties of primary rat cerebellar granule cells have been
      characterised with respect to their expression of GABAA receptor subtypes using
      both an immunological approach and radioligand binding assays. At day 1 in
      culture, the GABAA receptor alpha 1 subunit was detectable in immunoblots and
      increased in level up to day 9. The GABAA receptor alpha 6 subunit was not
      detectable at day 1; however, at days 3-5, a specific M(r) 58,000 anti-alpha 6 1
      16 Cys immunoreactive species was present which further increased in level up to
      9 days in culture. Similar qualitative results were obtained for the expression
      of the GABAA receptor alpha 6 subunit in age-matched rat cerebellar membranes. In
      parallel studies, it was found that although there was an overall increase in
      [3H]Ro 15-4513 binding sites with days in culture, the relative contributions of
      diazepam-sensitive and diazepam-insensitive [3H]Ro 15-4513 binding changed. A
      time-dependent enrichment of the diazepam-insensitive binding site up to a
      maximum of 74% of total [3H]Ro 15-4513 sites was found. This was concomitant with
      the appearance of the GABAA receptor alpha 6 subunit. These results are in
      agreement with the pharmacology described for alpha 6 beta gamma 2 cloned
      receptors. They suggest a developmentally regulated expression of the GABAA
      receptor alpha 6 subunit gene at a time that is correlated in vivo with
      establishment of neuronal connections.

PMID- 8158153
TI  - ADP-ribosylation of brain neuronal proteins is altered by in vitro and in vivo
      exposure to inorganic mercury.
AB  - ADP-ribosylation is an essential process in the metabolism of brain neuronal
      proteins, including the regulation of assembly and disassembly of biological
      polymers. Here, we examine the effect of HgCl2 exposure on the ADP-ribosylation
      of tubulin and actin, both cytoskeletal proteins also found in neurons, and B
      50/43-kDa growth-associated protein (B-50/GAP-43), a neuronal tissue-specific
      phosphoprotein. In rats we demonstrate, with both in vitro and in vivo
      experiments, that HgCl2 markedly inhibits the ADP-ribosylation of tubulin and
      actin. This is direct quantitative evidence that HgCl2, a toxic xenobiotic,
      alters specific neurochemical reactions involved in maintaining brain neuron
      structure.

PMID- 8158154
TI  - Intracerebroventricular administration of AT1 receptor antisense oligonucleotides
      inhibits the behavioral actions of angiotensin II.
AB  - Antisense oligonucleotides were developed to study the expression and function of
      angiotensin type 1 (AT1) receptors in cultured cells and brain. In both liver
      epithelial WB and neuroblastoma N1E-115 cells AT1 antisense oligomers
      substantially decreased AT1 receptor density, whereas angiotensin type 2 (AT2)
      receptors remained unchanged. Similarly, repeated intracerebroventricular
      injections of AT1 antisense oligomers in rats decreased AT1 receptor density in
      hypothalamic-thalamic-septal tissue, and AT2 receptors were unaffected.
      Intracerebroventricular antisense oligomers also attenuated drinking elicited by
      intracerebroventricular angiotensin II but not the cholinomimetic carbachol.
      Collectively, these results demonstrate that antisense oligonucleotides attenuate
      angiotensin receptor expression and function in behaving animals.

PMID- 8158155
TI  - Quinone-methide triterpenes and salaspermic acid from Kokoona ochracea.
AB  - Tingenone[1],20-hydroxy-20-epi-tingenone[2],celastrol[ 3], and salaspermic acid
      [4] have been isolated from Kokoona ochracea stem bark. The quinone-methide
      triterpenes 1-3 exhibited strong but non-specific in vitro cytotoxicity against P
      388 murine lymphocytic leukemia cells and a panel of human cancer cell lines.
      Salaspermic acid [4] was not active in all the cancer cell lines used in this
      investigation. 13C-nmr spectra assignments for salaspermic acid have been
      accomplished through the application of 1D and 2D nmr spectral techniques, and
      13C-nmr assignments for celastrol [3] have been revised.

PMID- 8158156
TI  - Two new cytotoxic peroxide-containing acids from a New Guinea sponge,
      Callyspongia sp.
AB  - Two new C14 cytotoxic, branched-chain acids, 1 and 2, containing a cyclic
      peroxide moiety were isolated from a sponge, Callyspongia sp., collected in New
      Guinea. The structures were elucidated through extensive spectral analysis.

PMID- 8158157
TI  - Isokotanins A-C: new bicoumarins from the sclerotia of Aspergillus alliaceus.
AB  - Three new bicoumarin metabolites, isokotanins A [1], B [2], and C [3], were
      isolated from the sclerotia of Aspergillus alliaceus. Isokotanin A is a
      regioisomer of the known bicoumarin kotanin [4]. The structures and spectral
      assignments for 1-3 were determined on the basis of selective INEPT, HMQC, and
      NOESY nmr data, as well as by chemical interconversions. Isokotanins B and C show
      activity against the corn earworm Helicoverpa zea and the dried fruit bettle
      Carpophilus hemipterus. The known compounds kotanin [4], desmethylkotanin [5],
      nominine, and paspaline were also isolated from extracts of A. alliaceus
      sclerotia.

PMID- 8158158
TI  - New cerebrosides from Euryale ferox.

PMID- 8158159
TI  - Novel HIV-inhibitory halistanol sulfates F-H from a marine sponge, Pseudoaxinissa
      digitata.
AB  - Three new steroid sulfates 2-4 related to halistanol sulfate [1] were isolated
      along with the known halistanol sulfate C [5] from the marine sponge
      Pseudoaxinissa digitata. Halistanol sulfates F [2] and G [3] proved to be
      cytoprotective against HIV.

PMID- 8158160
TI  - 8-Hydroxymanzamine A, a beta-carboline alkaloid from a sponge, Pachypellina sp.
AB  - The previously described manzamine A [1] and the new 8-hydroxymanzamine A [2]
      were isolated from an undescribed sponge, Pachypellina sp. Both compounds exhibit
      moderate antitumor and anti-HSV-II activity.

PMID- 8158161
TI  - The absolute configuration of ecklonialactones A, B, and E, novel oxylipins from
      brown algae of the genera Ecklonia and Egregia.
AB  - Ecklonialactones A, B, and E, previously isolated from the brown alga Ecklonia
      stolonifera, have been isolated from the Oregon phaeophyte Egregia menziesii. The
      structure and relative stereochemistry of ecklonialactone E were independently
      determined by various nmr techniques. The absolute stereochemistry of
      ecklonialactone A was deduced by cd analysis of a dibenzoate derivative, which
      indicated it possessed a 11S, 12R, 13S, 15R, 16S stereochemistry. Similar 1H- and
      13C-nmr data and optical rotations for all of the ecklonialactones indicate that
      B and E have the same stereochemistry as A at comparable stereocenters.

PMID- 8158162
TI  - Verongamine, a novel bromotyrosine-derived histamine H3-antagonist from the
      marine sponge Verongula gigantea.
AB  - The novel bromotyrosine derivative verongamine [1] has been isolated from the
      marine sponge Verongula gigantea. The isolation of verongamine was facilitated by
      employing histamine-H3 bioassay-guided fractionation. Verongamine is a specific
      histamine-H3 antagonist at concentrations as low as 1 microgram/ml.

PMID- 8158163
TI  - Cytotoxic and antibacterial dihydrochalcones from Piper aduncum.
AB  - Bioactivity-guided fractionation of a CH2Cl2 extract from the leaves of Piper
      aduncum afforded three new dihydrochalcones, piperaduncins A [3], B [4], and C
      [5], as well as two known dihydrochalcones, 2',6'-dihydroxy-4'
      methoxydihydrochalcone [1] and 2',6',4-trihydroxy-4'-methoxydihydrochalcone [2]
      (asebogenin), together with sakuranetin, anodendroic acid methyl ester, and the
      carotenoid lutein. The structures of the isolates were elucidated by
      spectroscopic methods, mainly 1D- and 2D nmr spectroscopy. The proposed
      stereochemistry for compound 4 was deduced by NOESY spectroscopy and the
      corresponding energy minimum was established by molecular modelling calculations
      and translated into a 3D structure.

PMID- 8158164
TI  - Anti-AIDS agents, 10. Acacetin-7-O-beta-D-galactopyranoside, an anti-HIV
      principle from Chrysanthemum morifolium and a structure-activity correlation with
      some related flavonoids.
AB  - An active anti-HIV principle, acacetin-7-O-beta-D-galactopyranoside, has been
      isolated from Chrysanthemum morifolium. Seven additional flavonoids isolated from
      this plant, 13 known related flavonoids, and 14 synthetic flavonoids were also
      evaluated as inhibitors of HIV replication in H9 cells. A known flavone, chrysin,
      was found to be the most promising compound in this series. Flavonoids with
      hydroxy groups at C-5 and C-7 and with a C-2-C-3 double bond were more potent
      inhibitors of HIV growth. In general, the presence of substituents (hydroxyl and
      halogen) in the B-ring increased toxicity and/or decreased activity.

PMID- 8158165
TI  - Isolation and structure of cephalostatins 10 and 11.
AB  - Further investigation of antineoplastic constituents from the marine worm
      Cephalodiscus gilchristi, employing a 450 kg re-collection from the Indian Ocean
      (Southeast Africa), has led to isolation and structural determination of two
      previously undetected members of the cephalostatin series, designated
      cephalostatins 10 [4] and 11 [5]. Structural analyses were conducted primarily
      employing high field 2D nmr and high resolution mass spectral techniques. All the
      stereochemical assignments were deduced using the original X-ray crystal
      structure of cephalostatin 1 and ROESY 2D nmr methods. Both cephalostatins 10 and
      11 strongly inhibited growth of a series of important human cancer cell lines.

PMID- 8158166
TI  - Isolation of bioactive and other oxoaporphine alkaloids from two annonaceous
      plants, Xylopia aethiopica and Miliusa cf. banacea.
AB  - The oxoaporphine alkaloids oxophoebine [1] and liriodenine [2] have been isolated
      from Xylopia aethiopica (Annonaceae). Both showed selective toxicity against DNA
      repair and recombination deficient mutants of the yeast Saccharomyces cerevisae.
      Three related but inactive compounds, oxoglaucine [3], O-methylmoschatoline [4],
      and lysicamine [5], were also isolated from this plant. Selective toxicity was
      also observed for 10-methoxyliriodenine (lauterine) [6] and 10-hydroxyliriodenine
      [7], two oxoaporphine alkaloids isolated from Miliusa cf. banacea (Annonaceae).
      The structure of 10-hydroxyliriodenine [7], a novel oxoaporphine, was determined
      by spectroscopic methods and chemical conversion to compound 6. The role of the
      bioactive oxoaporphine alkaloids as DNA topoisomerase inhibitors is discussed.

PMID- 8158167
TI  - New cycloartanol sulfates from the alga Tydemania expeditionis: inhibitors of the
      protein tyrosine kinase pp60v-src.
AB  - Bioactivity-directed fractionation of the extracts of the green alga Tydemania
      expeditionis using the protein tyrosine kinase pp60v-src led to the isolation of
      three new cycloartanol disulfates, 1-3, which show modest inhibition of this
      enzyme. The structures were deduced by spectroscopic methods.

PMID- 8158168
TI  - Discobahamins A and B, new peptides from the Bahamian deep water marine sponge
      Discodermia sp.
AB  - Discobahamin A [1] and discobahamin B [2] are two bioactive peptides isolated
      from a new species of the Bahamian deep water marine sponge Discodermia. The
      discobahamins are inhibitors of the growth of Candida albicans, and the isolation
      and structure elucidation of 1 and 2 by nmr and chemical methods is described.

PMID- 8158169
TI  - Naturally occurring antiacne agents.
AB  - Antibacterial activity of various secondary metabolites from plants against
      Propionibacterium acnes was tested. In addition, the study of combinations of
      compounds to enhance the total activity against this follicular bacterium was
      investigated. A series of long-chain alcohols was studied in great detail to gain
      new insights into the role of the hydrophobic alkyl groups in the activity.

PMID- 8158171
TI  - Marie Francois Xavier Bichat (1771-1802).

PMID- 8158170
TI  - Management of cervical spondylotic myelopathy and radiculopathy.

PMID- 8158172
TI  - Epilepsy.

PMID- 8158174
TI  - Hemifacial spasm.

PMID- 8158173
TI  - Differential diagnosis of Parkinson's disease, multiple system atrophy, and
      Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal 18F-dopa
      PET data.
AB  - Clinicopathological series indicate that the clinical diagnosis of Parkinson's
      disease is correct in only 80% of cases. Multiple system atrophy (MSA) and Steele
      Richardson-Olszewski syndrome (SRO) comprise most of the misdiagnoses. By means
      of 18F-dopa PET the pattern of nigrostriatal dopaminergic dysfunction in 28
      patients with clinically probable Parkinson's disease, 25 with MSA, and 10
      patients with SRO, was assessed and compared with the pattern in 27 normal
      subjects. Discriminant function analysis was used to assess the ability of 18F
      dopa PET to categorize individual parkinsonian patients on the basis of their
      caudate and putamen tracer uptake. Discriminant function analysis assigned all
      control subjects a normal category. One Parkinsonian patient out of 63 was
      classified as "normal" on the basis of PET findings, although this patient had
      significantly reduced putamen 18F-dopa uptake. Discriminant function analysis was
      less effective at distinguishing different categories of akinetic-rigid syndrome
      on the basis of their striatal 18F-dopa uptake, as judged against clinical
      criteria. Patients clinically labelled as having typical or atypical Parkinsonian
      syndromes were assigned the same category on PET criteria 64% and 69% of the
      time, respectively. When all three categories of Parkinson's disease, MSA, and
      SRO were considered together, clinical and 18F-dopa PET findings correlated in
      64% of patients assigned a diagnosis of Parkinson's disease and 70% of those
      given a diagnosis of SRO; MSA was less readily discriminated, patients with MSA
      being assigned to MSA, Parkinson's disease, and SRO groups with equal frequency.
      The correlation between clinical and discriminant function analysis assignment
      improved when separate comparisons were made between Parkinson's disease and MSA,
      or Parkinson's disease and SRO groups. In these analyses, clinical and PET
      categorisation of MSA and Parkinson's disease agreed in 60% of cases, and of SRO
      and Parkinson's disease in 90% of cases. In summary, (18)F-dopa PET successfully
      discriminates normal subjects from parkinsonian patients, and patients with
      Parkinson's disease from patients with SRO, but is less reliable in
      distinguishing Parkinson's disease from MSA. The concomitant assessment of
      striatal neuronal function with additional PET tracers may be necessary to
      reliably differentiate typical and atypical parkinsonian syndromes.

PMID- 8158175
TI  - Heterogeneity of neocortical cerebral blood flow deficits in dementia of the
      Alzheimer type: a [99mTc]-d,l-HMPAO SPECT study.
AB  - Regional cerebral blood flow (rCBF) was measured with high resolution brain
      dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l
      hexamethyl-propylene-amine-oxime (HMPAO) in 25 patients with probable Alzheimer's
      disease and in 25 control subjects, selected according to rigorous inclusion and
      exclusion criteria. The aim was to analyse the topography of rCBF deficits in
      individual patients. In the group of patients with Alzheimer's disease as a
      whole, global CBF was reduced, but a factorial analysis of variance did not show
      disproportionate reduction of rCBF in any brain region. A parametric analysis of
      the rCBF data in individual patients was carried out with reference to normal
      values for internal rCBF ratios and to 13 different abnormal rCBF patterns. These
      theoretical patterns were predefined by showing significant hypoperfusion in at
      least one, or in any relevant combination of two, three, or four, of four major
      brain regions (a left and right frontal and a left and right posterior region).
      All patients with Alzheimer's disease and none of the control subjects had an
      abnormal rCBF pattern. Eleven of the 13 different patterns were seen in the
      patients. Frontal changes were seen in 19 (76%) of the patients, more often than
      previously reported. No single Alzheimer's disease pattern could be derived from
      our data. The number of regions with hypoperfusion, but not the presence of
      frontal changes, correlated significantly with the duration of disease. It is
      concluded that a clinical diagnosis of probable Alzheimer's disease is associated
      with heterogeneous patterns of rCBF deficits as measured with SPECT and [99mTc]
      d,l-HMPAO. This heterogeneity may reflect different stages of the disease or
      cognitive subtypes and help explain published discrepancies concerning the
      topography of hypoperfusion in Alzheimer's disease. An analysis of individual
      rCBF data may add important information in the investigation of diseases with
      heterogeneous effects on the brain.

PMID- 8158176
TI  - Somatosensory evoked potentials after multisegmental upper limb stimulation in
      diagnosis of cervical spondylotic myelopathy.
AB  - Radial, median, and ulnar nerve somatosensory evoked potentials (SEPs) were
      recorded, with non-cephalic reference montage, in 38 patients with clinical signs
      of cervical myelopathy and MRI evidence of spondylotic compression of the
      cervical cord. Upper limb SEPs are useful in spondylotic myelopathy because SEPs
      were abnormal in all patients for at least one of the stimulated nerves and SEP
      abnormalities were bilateral in all patients but one. Reduction of the amplitude
      of the N13 potential indicating a segmental dysfunction of the cervical cord was
      the most frequent abnormality; it occurred in 93.4%, 84.2%, and 64.5% of radial,
      median, and ulnar nerve SEPs respectively. A second finding was that the P14 far
      field potential was more sensitive than the cortical N20 potential to slowing of
      conduction in the dorsal column fibres. The high percentage of N13 abnormalities
      in the radial and median rather than in the ulnar nerve SEPs correlated well with
      the radiological compression level, mainly involving the C5-C6 vertebral
      segments. Therefore the recording of the N13 response is a reliable diagnostic
      tool in patients with cervical spondylotic myelopathy and P14 abnormalities,
      though less frequent, can be useful in assessing subclinical dorsal column
      dysfunction.

PMID- 8158177
TI  - Electrophysiological assessment of central and peripheral motor routes to the
      lingual muscles.
AB  - Compound muscle action potentials (CMAPs) of the lingual muscles were recorded by
      especially devised bipolar surface electrodes placed on the tongue. Distinct
      responses were evoked in the tongue muscles by peripheral electrical stimulation
      of the hypoglossal nerve medial to the angle of the jaw and by transcranial
      magnetic stimulation of the motor cortex. With cortical stimulation during
      voluntary activation of the tongue muscles it proved easy to obtain responses
      with the characteristics of centrally evoked responses allowing reliable
      measurements of latencies and amplitudes. By contrast, responses from magnetic
      stimulation of the intracranial segment of the hypoglossal nerve were more
      difficult to obtain and the reproducibility was often not satisfactory. In a
      group of 20 healthy subjects the average distal motor latency of both sides from
      peripheral stimulation was 2.4 ms and the corresponding amplitude was 9.3 mV on
      the left and 8.6 mV on the right side (range 5.1-16.0 mV). Cortical stimulation
      gave responses with an average onset latency of 8.6 ms and 8.8 ms and an average
      amplitude of 1.8 mV and 2.6 mV on the left and right sides of the tongue
      respectively (range 0.7-5.6 mV). From this mean conduction times of 6.2 ms on the
      left and 6.4 ms on the right side (SD 1.0 ms) between cortex and mandibular angle
      and relative amplitudes from cortical stimulation as compared with the peripheral
      CMAP of 29% on the left and 21% on the right side (range 7%-66%) were calculated.
      In 16 patients it was possible to differentiate between a central (supranuclear)
      and a peripheral (intranuclear) site for the lesions of the motors routes to the
      lingual muscles and to show subclinical lesions in some cases. With a recording
      arrangement allowing selective unilateral recording of muscle activity from both
      sides of the tongue the assumed bihemispheric motor representation of the lingual
      muscles was confirmed.

PMID- 8158178
TI  - Robert Bentley Todd (1809-60) and Todd's paralysis.

PMID- 8158179
TI  - Reflex myoclonus in olivopontocerebellar atrophy.
AB  - The presence of reflex myoclonus in response to touching and pin-pricking the
      wrist or stretching the fingers and to photic stimulation was assessed in 24
      patients with a presumed diagnosis of olivopontocerebellar atrophy (OPCA) and in
      30 age matched control subjects. Reflex myoclonus to soma-esthetic stimulation
      was found in 23 patients and in none of the controls. Photic myoclonus was
      present in 12 patients and in none of the controls. Electrophysiological study of
      the reflex myoclonus showed enhanced (> 10 microV) somatosensory evoked
      potentials and an associated reflex electromyographic discharge (C-wave) in 15
      patients. These findings indicate that reflex myoclonus is common in OPCA and
      probably of cortical origin.

PMID- 8158180
TI  - The characteristics of epilepsy in a largely untreated population in rural
      Ecuador.
AB  - A house-to-house survey of epileptic seizures covering a population of 72,121
      persons was carried out in a rural area of northern Ecuador. A cascade system of
      diagnosis was used to identify all cases of epileptic seizures in this
      population. 1029 cases were found, of whom 881 were considered to be definite
      cases and 148 were possible cases. Of the 1029 cases, 56% had active epilepsy.
      The lifetime prevalence rate was found to lie between 12.2 and 19.5/1000 and the
      prevalence of active cases between 6.7 and 8.0/1000. An annual incidence rate of
      between 122/100,000 and 190/100,000 was estimated. Seizure type was classified
      without EEG data and almost half of the cases had partial seizures. In 27% of
      cases an aetiology was proposed on clinical grounds. This is one of few reported
      studies of a population that has been largely unexposed to antiepileptic drugs,
      providing an opportunity to study the natural history of the untreated condition.
      It has been suggested that treatment in newly developing epilepsy will prevent
      its development to a chronic condition. Only 37% of the 1029 cases had ever
      received antiepileptic drugs, and only 12% of the cases were taking them at the
      time of the survey. Despite this, a high rate of inactivity was observed, with
      44% of all cases free of seizures. Nearly two thirds of the inactive cases
      identified had never received treatment with antiepileptic drugs. In a subgroup
      of untreated cases with an active condition, treatment with antiepileptic drugs
      was initiated and was highly effective even in cases with a long previous
      history. Thus the findings from this study suggest that the development of
      epilepsy resistant to therapy is not always associated with a long duration of
      untreated epilepsy.

PMID- 8158181
TI  - Accuracy, reproducibility, and variability of hand-held dynamometry in motor
      neuron disease.
AB  - A spring-loaded device that "breaks" at preset forces was used to assess readings
      obtained by hand-held dynamometry by three raters with varying experience in the
      method. Overall accuracy (3%), but not reproducibility or variability, was
      improved by greater experience. Readings obtained jointly by three raters had 53%
      greater variability than those obtained by a single rater. Nine muscle groups in
      19 patients with motor neuron disease were assessed at 10 sessions (three
      replications per session) over six days by the experienced rater. Muscle force
      was expressed relative to that of 22 matched normal controls. The reproducibility
      was good with a mean % difference of 13.2 and repeatability coefficient of 2.17
      kg-force for readings six days apart; the overall correlation coefficient was
      0.98. The mean coefficient of variation (CV) of 10 readings was 9.9%. The poorer
      reproducibility and greater variability seen in clinically weaker muscles may
      account for differences in patients with bulbar palsy and classical amyotrophic
      lateral sclerosis; the degree of spasticity had no effect. The rater was
      estimated to contribute 37% of the total variability when testing patients. The
      use of a composite score by combining normalised dynamometry readings of eight
      limb muscles improved mean % difference to 6.7 and mean CV to 5.8%. The
      reproducibility and variability of hand-held dynamometry readings obtained by a
      single rater compare well with those of fixed devices. Readings from single
      raters, irrespective of experience, have similar reproducibility and variability.
      If, however, multiple raters are used in longitudinal assessments of individual
      patients, as occurs in clinical trials, the variability of their combined
      readings should be estimated when calculating the same size required.

PMID- 8158182
TI  - Drug refractory epilepsy in brain damage: effect of dextromethorphan on EEG in
      four patients.
AB  - High doses of dextromethorphan (20-42 mg/kg/day) were given to four critically
      ill children with seizures and frequent epileptiform abnormalities in the EEG
      that were refractory to antiepileptic drugs. Their acute diseases (hypoxia, head
      trauma and hypoxia, neurodegenerative disease, hypoglycaemia) were thought to be
      due in part to N-methyl-D-aspartate (NMDA) receptor mediated processes. Treatment
      with dextromethorphan, an NMDA receptor antagonist, was started between 48 hours
      and 14 days after the critical incident. In three patients the EEG improved
      considerably within 48 hours and seizures ceased within 72 hours. In the patient
      with neurodegenerative disease the effect on the EEG was impressive, but the
      seizures were not controlled. Despite the improvement of the EEG the clinical
      outcome was poor in all children: three died in the critical period or due to the
      progressing disease; the patient with hypoglycaemia survived with severe
      neurological sequelae. Plasma concentrations of dextromethorphan varied between
      74-1730 ng/ml and its metabolite dextrorphan varied between 349-3790 ng/ml. In
      one patient corresponding concentrations in CSF were lower than those in plasma.
      The suppression of epileptic discharges by the doses of dextromethorphan given
      suggests that such doses are sufficient to block NMDA receptors.

PMID- 8158183
TI  - Antiarrhythmic drugs and polyneuropathy. The Collaborative Group for the Study of
      Polyneuropathy.
AB  - A total of 151 patients on chronic treatment with amiodarone and other
      antiarrhythmic drugs were subjected to standard clinical and electrophysiological
      investigation to assess the prevalence and specificity of polyneuropathy. Twenty
      two untreated patients with cardiac disorders and 246 normal subjects served as
      controls. Abnormal electrophysiological findings supporting the diagnosis of
      polyneuropathy were present in 38 subjects (25%) given antiarrhythmic drugs, with
      even distribution among drugs, and four untreated patients (18%). Concurrent
      clinical abnormalities were present in five treated patients (one each with
      amiodarone, propafenone, and flecainide, and two with multiple drugs). Therefore,
      electrophysiological abnormalities are a common, although non-specific, feature
      in patients taking antiarrhythmic drugs. Amiodarone users do not seem at higher
      risk of polyneuropathy than subjects treated with other drugs or even untreated
      patients with cardiac disorders.

PMID- 8158184
TI  - Benign familial disease with muscle mounding and rippling.
AB  - Four members of a family in three generations exhibited unusual clinical features
      of localised transient swelling of muscle induced by percussion (muscle mounding
      or myoedema) and were able, voluntarily, to induce rhythmic waves of contraction
      in certain muscles (muscle rippling or rolling). All had raised serum creatine
      kinase activity. Muscle biopsy in two members showed no specific abnormality.
      Experimental studies performed on excised intercostal muscle showed that abnormal
      "after-contractions" and increased sarcolemmal excitability could be demonstrated
      in vitro.

PMID- 8158185
TI  - The neck-tongue syndrome.
AB  - The neck-tongue syndrome, consisting of pain in the neck and altered sensation in
      the ipsilateral half of the tongue aggravated by neck movement, has been
      attributed to damage to lingual afferent fibres travelling in the hypoglossal
      nerve to the C2 spinal roots. The lingual afferents in the hypoglossal nerve are
      thought to be proprioceptive. Two further cases of the neck-tongue syndrome are
      described, the spectrum of its clinical manifestations is explored, and the
      phenomenon of lingual pseudoathetosis is illustrated as a result of the presumed
      lingual deafferentation.

PMID- 8158187
TI  - Robert Bentley Todd (1809-60) and locomotor ataxia.

PMID- 8158186
TI  - Dementia in two histologically confirmed cases of multiple sclerosis: one case
      with isolated dementia and one case associated with psychiatric symptoms.
AB  - During the past 10 years, considerable attention has been devoted to cognitive
      impairment in multiple sclerosis. Occasionally this impairment may be so severe
      that multiple sclerosis presents as a dementia associated with only minor
      neurological signs and symptoms. The cases of two women affected by multiple
      sclerosis who presented with a pure dementia are reported. In the first patient,
      a progressive apragmatic behavioural disturbance with reduced short term memory
      and learning abilities were the main clinical features. Neuropathological
      examination of the brain disclosed numerous plaques in the periventricular white
      matter, with severe atrophy of the corpus callosum. Plaques were also seen in the
      white matter of both hippocampus and in the columns of the fornix. The impairment
      of short term memory could be linked to these lesions. Behavioural changes were
      probably related to the bilateral lesions of the long associative bundles that
      disconnected the frontal lobes from other parts of the cerebral hemispheres. In
      the second patient, visual hallucinations were associated with cognitive
      dysfunction. MRI showed large plaques in the white matter of both left frontal
      and temporal lobes. Smaller plaques were also present in the periventricular
      white matter of the occipital lobes, the nature of which were confirmed by a
      stereotactic biopsy.

PMID- 8158188
TI  - A central executive deficit in patients with Parkinson's disease.
AB  - Eight patients with Parkinson's disease and eight matched controls were tested
      for concurrent task performance to examine whether Parkinson's disease produces
      deficits in the coordinating and integrating function of the central executive
      component of Baddeley's working memory model. Consistent with this prediction,
      the patients showed a significant decline in performance on a random pursuit
      tracking task while recalling digit span forward sequences, whereas the controls
      showed no such change. Performance on the component pursuit and digit span tasks,
      which did not differ between groups, was equated across subjects by varying the
      size of a target square and by using individual subjects' digit spans. The
      patient group also produced poorer word fluency scores and reported higher levels
      of depression, but there was no significant impairment on the Wisconsin card sort
      test. There was no association between dual task performance and any psychometric
      measure, target size, or disease related variables. Baddeley's working memory
      model is advantageous in providing a rich conceptual basis to explore and
      characterise cognitive abilities in patients with Parkinson's disease.

PMID- 8158189
TI  - Reduction in external cues and movement sequencing in Parkinson's disease.
AB  - To identify the focus of impairment in the performance of sequential movements of
      patients with Parkinson's disease, the extent of their reliance on external cues
      was examined. Eighteen patients with idiopathic Parkinson's disease and their
      matched controls performed a series of button presses at sequential choice points
      along a response board. The illuminated pathway to be followed successively
      extinguished ahead of each move according to three levels of reduction of
      external cues. Patients with Parkinson's disease were particularly disadvantaged
      with high levels of reduction of external cueing in terms both of movement
      preparation time (button down time) and movement execution time (movement time
      between buttons). Moreover, with high levels of reduction of external cueing,
      patients with Parkinson's disease were particularly subject to progressive
      slowing (movement time, not down time) further down the sequence. The basal
      ganglia may help generate internal cues for releasing successive stages of a
      predefined movement sequence.

PMID- 8158190
TI  - Birth injury as a causative factor of syringomyelia with Chiari type I deformity.
AB  - The epidemiology of syringomyelia with Chiari type I deformity was investigated
      with particular reference to perinatal problems. All subjects in our study were
      born by vaginal delivery and had a high incidence of perinatal accidents
      (abnormal presentations, birth injuries, and neonatal asphyxia). This study
      suggests that these may be strong causative factors for syringomyelia associated
      with Chiari type I deformity.

PMID- 8158191
TI  - Single fibre EMG studies in chronic fatigue syndrome: a reappraisal.
AB  - Single fibre EMG studies were carried out on the right extensor digitorum
      communis muscle in 30 subjects with chronic fatigue syndrome and in 30 age and
      sex matched controls. Abnormal jitter was seen in five patients with chronic
      fatigue syndrome. Slight but significant differences between the mean consecutive
      differences in the remainder of the chronic fatigue subjects and the control
      subjects were recorded. Overall the differences were so minor that it seems
      unlikely that a disturbance of neuromuscular function as reflected by jitter
      measurement has a pathogenetic role. It is suggested that the increased jitter
      seen may be explained by the effects of the variability of motor unit firing
      rates on the myogenic component of the jitter.

PMID- 8158192
TI  - Brain failure in private and public life: a review.

PMID- 8158193
TI  - Isolated intracranial hypertension presenting with trigeminal neuropathy.

PMID- 8158194
TI  - Spinal intrathecal baclofen suppresses central pain after a stroke.

PMID- 8158195
TI  - Effect of immobilisation on position and movement sense of the knee.

PMID- 8158196
TI  - Worsening of myasthenia gravis on treatment with imipenem/cilastatin.

PMID- 8158197
TI  - Acceptability of electroconvulsive therapy to patients with Parkinson's disease.

PMID- 8158198
TI  - Case report: dysphagia and sleep apnoea associated with cervical osteophytes due
      to diffuse idiopathic skeletal hyperostosis (DISH)

PMID- 8158199
TI  - Horologagnosia: an impairment of the ability to tell the time.

PMID- 8158200
TI  - The coin-in-the-hand test: a new "bed-side" test for the detection of malingering
      in patients with suspected memory disorder.

PMID- 8158201
TI  - 123rd Meeting of the Society of British Neurological Surgeons. Birmingham, United
      Kingdom, 3-6 November 1993. Abstracts.

PMID- 8158202
TI  - Clinical implementation of anti-acetylcholine receptor antibodies.

PMID- 8158203
TI  - Reactive microglia in multiple sclerosis lesions have an increased expression of
      receptors for the Fc part of IgG.
AB  - Receptors for the Fc part of IgG, FcRI (CD64), FcRII (CD32), and FcRIII (CD16)
      were studied by indirect immunoperoxidase staining of cryostat sections from
      normal and multiple sclerosis (MS) brains. Microglia in the parenchyma of normal
      white matter had a dendritic morphology, and were weakly stained by monoclonal
      antibodies (mAbs) to FcRI, FcRII, and FcRIII. In active MS lesions reactive
      microglia were strongly stained by the mAbs 32.2 (FcRI), IV-3 (FcRII), and 3G8
      (FcRIII). Perivascular macrophages were stained by all anti-FcR mAbs in both
      normal white matter and in MS lesions, whereas endothelial cells were stained by
      the anti-FcRIII mAb only. The FcR on microglia and perivascular macrophages may
      be of functional importance in antibody-dependent cell-mediated cytotoxicity
      (ADCC), phagocytosis, and local immunoregulation. FcR on endothelium may be of
      importance in binding and transportation of immune complexes into the CNS. FcR
      mediated functions may consequently be highly relevant to the pathogenesis of MS.

PMID- 8158204
TI  - Presence of neuronal proteins in serially cultured cells from autopsy human
      brain.
AB  - Cells that contain the high (NF-H) and medium (NF-M) molecular weight
      neurofilaments and neuron-specific enolase (NSE) have been cultured from human
      brain (Brodmann frontal area 9 and hippocampus) obtained at routine autopsy.
      Three of these cultures (from a 52-year-old man with vascular dementia, a 75-year
      old man with Alzheimer's disease, and an 80-year-old normal woman) have been
      propagated to passage 12-14 and studied in detail. Cellular morphology was
      pleomorphic and consistent with a relatively low level of differentiation, by
      both light microscopic and ultrastructural examination. Immunocytochemical
      reactivity in a characteristic filamentous pattern was observed with monoclonal
      antibodies to nonphosphorylated epitopes of NF-H and NF-M as well as with
      redundant antibody probes specific for NF-H and NF-M. Immunoblotting studies
      confirmed the presence of NF-H and NF-M. Immunocytochemistry and Immunoblotting
      also demonstrated the presence of NSE, but not of glial fibrillary acidic protein
      or other glial markers. Immunocytochemical studies also indicated the presence of
      proline hydroxylase, an enzyme found in fibroblasts but not neurons. These
      studies indicate that cells can be cultured from autopsy human brain which are
      not neurons but nevertheless express molecules used as markers (NF-H, NF-M, and
      NSE) of adult neurons in vivo and in culture.

PMID- 8158205
TI  - Somatosensory event-related potentials (ERPs) in patients with different types of
      dementia.
AB  - Somatosensory ERPs and short latency somatosensory evoked potentials (SSEPs) were
      studied in patients with dementia of the Alzheimer type (DAT), those with
      vascular dementia, demented and non-demented patients with Parkinson's disease,
      and healthy control subjects. In control subjects, latencies of N140, P200, N240
      and P300 components increased with age at a rate of 0.2, 0.2, 0.6 and 1.5
      msec/year, respectively. Patients with DAT and demented patients with Parkinson's
      disease had normal SSEPs as well as normal P100, and N140 latencies, but patients
      with vascular dementia showed prolonged N140 and P200 latencies in addition to a
      prolonged central conduction time (CCT). Analysis of N140 and P200 components of
      somatosensory ERPs may be important for evaluation of patients with vascular
      dementia. In patients with DAT, those with vascular dementia and demented
      patients with Parkinson's disease, the P300 latency was significantly prolonged
      compared with that in age-matched control subjects. However, the P300 latency did
      not show any significant differences among the groups of demented patients.

PMID- 8158206
TI  - Muscle tone in Huntington's disease.
AB  - Tone was evaluated quantitatively in 39 patients with Huntington's disease (HD)
      by measuring resistance to passive elbow flexion and extension movements on a
      hydraulic testing device. A velocity dependent increase in resistance to passive
      elbow flexion and to a lesser extent in resistance to passive extension was found
      in 10 patients. Increase in muscle tone was related to disease duration but not
      to the age of the patients nor to the severity of choreatic movements or the
      amount of cognitive impairment. A hypertonic pattern could be observed also in
      patients without any medication, and seemed not to be related to neuroleptic
      treatment. The pattern of tone change in HD is compared to the pattern of
      hemispasticity in upper motor neuron syndrome and to that of Parkinson's disease.
      It appears that an increase in muscle tone, with a velocity dependent resistance
      to flexion more than extension movements, is a frequent feature in advanced
      stages of Huntington's disease.

PMID- 8158207
TI  - Subacute sensory neuropathy associated with Hodgkin's disease.
AB  - We describe 2 patients with Hodgkin's disease (HD) who developed a subacute
      predominantly sensory neuropathy with areflexia, which improved after tumour
      removal, and review 6 cases with sensory neuropathies associated with HD from the
      literature. The neuropathy revealed a relapse of the tumour in patient 1 and was
      the presenting feature of HD with Castleman's disease-like lesions in patient 2.
      Nerve conduction velocities were normal, sensory and motor potential amplitudes
      were reduced, and F waves were increased. Unlike sensory ganglionitis associated
      with small cell lung cancer, sensory evoked potentials were not abolished. Nerve
      biopsies showed axonal degeneration and mild perivascular inflammatory
      infiltrates. We believe that the cases of subacute sensory neuropathies
      associated with HD that show dramatic improvement after treatment of the
      underlying tumour correspond to a variant of HD-associated inflammatory
      demyelinating polyneuropathy rather than to a true paraneoplastic sensory
      ganglionitis.

PMID- 8158208
TI  - Glucose and leucine uptake by rat dorsal root ganglia is not insulin sensitive.
AB  - Dorsal root ganglia from rats were incubated with 3-O-methyl-[14C]glucose, and
      [3H]leucine in the presence or absence of insulin in order to determine whether
      insulin influences the uptake of glucose and amino acids by the cells of the
      ganglion. No effect was detected. A significant proportion (38%) of the uptake of
      [3H]leucine was shown to be inhibited by ouabain and therefore energy dependent,
      utilizing Na+K(+)-ATPase. The activity of this enzyme is known to be impaired in
      dorsal root ganglia in diabetic rats, as is the uptake of amino acids; these
      phenomena are therefore unlikely to be due to a direct effect of reduced
      circulating insulin levels. The relevance of these findings to theories as to the
      causation of diabetic neuropathy is discussed.

PMID- 8158209
TI  - Low contents of nerve growth factor in serum and submaxillary gland of diabetic
      mice. A possible etiological element of diabetic neuropathy.
AB  - Insulin and nerve growth factor are peptides that share several chemical and
      functional properties. While the total or relative deficiency of insulin causes
      diabetes, the possible disorders due to deficiency of nerve growth factor have
      not been clearly defined. However, the intense biological actions of nerve growth
      factor in the maintenance and growth of several neural cells make feasible its
      participation in the physiopathology of some diseases of the peripheral nervous
      system. We measured the contents of nerve growth factor in serum, submaxillary
      gland and sciatic nerve of mice with streptozotocin-induced diabetes. Nerve
      growth factor in diabetic mice was diminished in serum and submaxillary gland
      when compared with matched controls (P < 0.01). This finding further supports a
      similar observation in diabetic patients and suggests a possible etiological
      involvement of neural growth factor in the development of diabetic neuropathy.

PMID- 8158210
TI  - Aberrant androgen action and increased size of tandem CAG repeat in androgen
      receptor gene in X-linked recessive bulbospinal neuronopathy.
AB  - Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH) after 3 or 6 days of administration of the synthetic androgenic
      hormone fluoxymesterone (10 mg/day) were measured in 26 patients with X-linked
      recessive bulbospinal neuronopathy (X-BSNP) and 22 age-matched male controls. The
      testosterone, LH and FSH levels in the controls were markedly suppressed after
      administration, but in the patients with X-BSNP, they were suppressed
      significantly less. The level of suppression varied considerably with the
      patients, and those of plasma testosterone and FSH were significantly correlated
      with the number of CAG repeats in the androgen receptor gene. These findings
      suggest that the androgen action was aberrantly transduced in the target organs
      in the patients with X-BSNP and which is related to the elongated CAG repeat in
      the androgen receptor gene.

PMID- 8158211
TI  - High sciatic lesion mimicking peroneal neuropathy at the fibular head.
AB  - We report 4 patients with severe, axon-loss, high sciatic mononeuropathies
      affecting exclusively the peroneal fibers: a boy with a slowly-growing nerve
      tumor, a woman with an injection injury, and 2 patients who had undergone
      proximal femur surgery. Clinically, the findings mimicked those seen with common
      peroneal neuropathy at the fibular head. The peroneal conduction studies were
      very low in amplitude/unelicitable. Conversely, the tibial studies and H
      responses were normal in all; the sural responses were normal in one while low in
      amplitude/unelicitable in the remaining three. The biceps femoris, short-head,
      and all peroneal-innervated muscles showed fibrillations and profound motor unit
      loss. Conversely, the remaining hamstrings and all tibial-innervated muscles were
      normal. We conclude that a sciatic lesion can imitate a more distal peroneal
      lesion. Needle EMG of the biceps femoris, short head, is essential for correct
      diagnosis.

PMID- 8158212
TI  - Changes in nerve growth factor content of the submaxillary gland in the
      genetically dystrophic (mdx) mouse.
AB  - We evaluated the nerve growth factor (NGF) contents in the submaxillary gland of
      the mdx mouse, a model for Duchenne muscular dystrophy (DMD), and found that the
      NGF and NGF mRNA contents in this organ, where extraordinarily high amounts of
      NGF are synthesized and stored independently of development or maintenance of the
      nervous system, were markedly elevated in the male mdx mouse at 8 and 11 weeks of
      age. However, the NGF content of this organ in 4-week-old male mdx mice was lower
      than that of control mice although statistical significance of difference was not
      observed. In the mdx female mouse, the submaxillary NGF content was significantly
      lower than that of the normal mouse at 4 weeks of age, but was similar to that of
      the normal at 8 and 11 weeks of age. The amounts of epidermal growth factor
      (EGF), another protein that is known to be sexually and developmentally regulated
      in the mouse submaxillary gland like NGF, was found to be also significantly
      increased in this organ of the male mdx mouse at 8 and 11 weeks of age, and to be
      significantly decreased in that of the female mdx mouse at 4 weeks of age. The
      parallel changes in NGF and EGF contents during development of the submaxillary
      gland suggest that the mdx mouse suffers from some abnormality in the development
      of this organ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158213
TI  - Multiplicity of abnormal dystrophin in Becker muscular dystrophy. A Becker
      muscular dystrophy gene frequently produced two smaller sizes of dystrophin.
AB  - Dystrophin is a muscle cytoskeletal protein with a molecular mass (MM) of
      approximately 420 kDa and an isoelectric point (pI) of approximately 5.5, which
      is abnormal in size and/or abundance in Becker muscular dystrophy (BMD). We
      investigated the abnormality of dystrophin molecule in muscles biopsied from 23
      BMD patients using the two-dimensional gel electrophoresis (TDGE). We found 7
      protein spots which reacted specifically with the monoclonal anti-dystrophin
      antibody (mAb) A1C raised against N-terminal domain of the normal dystrophin.
      These spots were focused on the two-dimensional gel at the same position as the
      normal dystrophin (#1), at the position with MM approximately 480 kDa/pI
      approximately 5.35 (#2), the position with MM approximately 400-330 kDa/pI
      approximately 5.51-5.47 (#3), the position with MM approximately 300 kDa/pI
      approximately 5.4 (#4), the position with MM approximately 235-250 kDa/pI
      approximately 5.53-5.5 (#5), the position with MM approximately 165 kDa/pI
      approximately 6.0 (#6), and the position with MM approximately 160 kDa/pI
      approximately 5.75 (#7). These spots were classified into five patterns in
      individuals, that is, #1 alone in 3 patients, #3 alone in 1, the combination of
      #3 and 5 in 17, the combination of #1, 3 and 5 in 1 and the combination of #1, 2,
      4, 6 and 7 in 1. The combination of #3 and 5 was observed in 17 of 23 patients
      (75%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158214
TI  - beta-Bungarotoxin binding protein is immunogenic but lacks myasthenogenicity in
      rats.
AB  - Myasthenia gravis is an autoimmune disease resulting from autoaggressive immunity
      to the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction.
      Immunization with AChR leads to experimental autoimmune myasthenia gravis (EAMG).
      AChR binds to alpha-bungarotoxin, and this property is utilized to purify AChR.
      The utilization of beta-bungarotoxin (beta-BGT) allows the purification of a
      different protein of striated muscle. To examine the myasthenogenic activity of
      the beta-BGT binding protein, we immunized Lewis rats with the beta-BGT binding
      protein or AChR from Torpedo. While AChR-immunized rats developed typical signs
      of EAMG, beta-BGT binding protein immunized rats showed no definite clinical
      signs of muscular weakness during observation periods up to 14 weeks after
      immunization. High levels of anti-AChR IgG antibodies and low levels of
      antibodies against beta-BGT binding protein were present in the AChR-immunized
      rats, while high levels of IgG antibodies to the beta-BGT binding protein and low
      anti-AChR IgG antibody levels were found in the rats immunized with the beta-BGT
      binding protein. No relationship was observed between antibody levels and
      severity of EAMG. The anti-AChR and anti-beta-BGT binding protein IgG antibodies
      showed only low degrees of cross-reactivity. We conclude that the beta-BGT
      binding protein is immunogenic also in EAMG, while it is still an open question
      whether it also has myasthenogenic properties.

PMID- 8158215
TI  - Fibre size, atrophy, and hypertrophy factors in vastus lateralis muscle from 18-
      to 29-year-old men.
AB  - In order to study the size of muscle fibres, cross-sections of autopsied vastus
      lateralis muscle from 8 healthy men, aged 18 to 29 years, who have died suddenly
      were prepared and analyzed. Data were obtained on cross-sectional area, on lesser
      diameter, and on atrophy and hypertrophy factors of type 1 and type 2 fibres,
      subdivided into 2a, 2b, and 2c fibres. The difference in mean fibre size between
      type 1 and 2 fibres was not significant, whereas the differences between type 1
      and 2b, type 1 and 2a, and type 2a and 2b fibres were significant. In the whole
      material type 2a fibres were the largest and type 2b fibres the smallest. There
      were considerable differences between post-mortem subjects. Because of these
      differences and the variability of all fibre types in respect of size in a sample
      the normal ranges of fibre size were large. The normal ranges and a continuous
      scale of weights were used to determine the atrophy and hypertrophy factors in
      each sample, and the upper limits of these factors accepted as being normal. The
      estimates of the limits of normality of the area, diameter, atrophy and
      hypertrophy factors of type 1, 2, 2a and 2b fibres reflect the situation in the
      vastus lateralis muscle of healthy young men. These values might be useful in
      studying physiological and pathological conditions influencing the size of
      different fibre types.

PMID- 8158216
TI  - Does muscular dystrophy affect metabolic rate? A study in mdx mice.
AB  - In this study metabolic consequences of muscular dystrophy were investigated
      using the mdx mouse model. Measurements were performed on C57BL/10SNJ (control)
      and dystrophic (mdx) mice of ages 4-6 weeks (young) and 1 year (adult), i.e. at
      times when muscle degeneration and regeneration are known to be high (young) and
      low (adult). Whole body metabolic rate (MR) was measured indirectly under usual
      living conditions by recording O2 consumption and CO2 production over 24 h.
      Physical activity of mice was measured simultaneously. Oxygen consumption of
      soleus (SOL) and extensor digitorum longus (EDL) muscles of control and mdx mice
      was recorded in vitro, using polarographic O2 electrodes. MR in young mdx was
      significantly decreased compared to young control, but no differences were found
      in adults. Also, food consumption and physical activity of mdx were decreased
      significantly compared to control in young but not in adult mice. There was no
      difference in resting oxygen consumption of muscles from young mdx and control
      mice, but oxygen consumption of EDL from adult mdx was less than control. Results
      suggest that muscular dystrophy results in decreased rate of energy metabolism
      mainly as a consequence of decreased physical activity. The extensive muscular
      degeneration and regeneration characteristic of muscular dystrophy therefore do
      not appear to lead to an increase in whole body metabolism.

PMID- 8158217
TI  - Production of granulocyte-macrophage colony stimulating factor by human T
      lymphotropic virus type I-infected human glioma cells.
AB  - We investigated the production of granulocyte-macrophage colony stimulating
      factor (GM-CSF) by human T-lymphotropic virus type I (HTLV-I)-infected human
      glioma cells (KG-1-C and T98G). When glioma cells were co-cultured with HTLV-I
      producing T cell lines (HCT-1 and MT-2), GM-CSF was detected in the culture
      supernatant. GM-CSF was produced in all the co-cultures even after several
      passages. In co-cultures of KG-1-C and HCT-1 cells with Millicell, the amount of
      GM-CSF produced in the supernatant was almost as low as in the culture of HCT-1
      alone. Moreover, for co-cultures of KG-1-C and HCT-1 or MT-2 cells, the
      production of GM-CSF was significantly suppressed in the presence of IgG from
      patients with HAM. Double-label immunostaining showed that GM-CSF-producing
      glioma cells always were stained by a monoclonal antibody against HTLV-I p19,
      indicating that HTLV-I infection of glioma cells caused GM-CSF production. These
      data suggest that human glial cells infected with HTLV-I gain the ability to
      produce cytokines.

PMID- 8158218
TI  - A pathologically distinct new form of HIV associated encephalopathy.
AB  - We present the clinical, morphological and neuropathological findings in a 44
      year-old male suffering from the acquired immunodeficiency syndrome (AIDS) (CDC
      stage IV C2) who presented with rapidly progressive right-side hemiparesis and
      developed hemianopia and aphasia. Scans showed multiple, not contrast-enhancing,
      not space-occupying echo-intensive lesions in T2-weighted MR-imaging. No hint for
      an opportunistic infection, necrotizing vasculitis or vascular disease was found.
      All therapeutic regimens failed and 8 weeks after onset of neurological symptoms
      the patient died because of cardiorespiratory arrest. Post-mortem examination
      excluded opportunistic infection, progressive multifocal leukoencephalopathy,
      lymphoma, vasculitis and ischemia of the brain. In the presence of an unusually
      high amount of HIV-infected macrophages at immunohistochemical examination, the
      overall pathological findings were atypical both for HIV encephalitis and HIV
      leukoencephalopathy. We describe a pathologically distinct new form of HIV
      associated encephalopathy.

PMID- 8158220
TI  - LDL-apheresis cannot be recommended for treatment of cerebrotendinous
      xanthomatosis.

PMID- 8158219
TI  - Long-term changes in cerebral blood flow according to different types of ischemic
      stroke.
AB  - Recurrence of ischemic stroke may be related to chronic hemodynamic failure of
      the brain. Long-term changes in cerebral blood flow (CBF) remain undetermined for
      each ischemic stroke subtype. We performed the present study to clarify this
      issue. The study group consisted of 77 unilateral, hemispheric, ischemic stroke
      patients who had a single stroke episode; atherothrombotic stroke in 34,
      cardioembolic in 26 and lacunar in 17. We measured baseline CBF in the affected
      and unaffected hemispheres 1.0-3.4 months after stroke onset, then repeated the
      measurements 10 months to 10 years later (mean 43.7 months), with the xenon-133
      inhalation method. We analyzed changes in CBF in relation to other clinical
      characteristics. CBF in the affected hemisphere changed differently among the
      stroke subtypes (P < 0.01); increased in the atherothrombotic group, particularly
      within 40 months of stroke; remained unchanged in the cardioembolic group; and
      decreased in the lacunar group, especially later than 40 months of stroke. In the
      atherothrombotic group, CBF increased in hypertensive patients but decreased in
      normotensives (7.9 +/- 2.4% and -3.6 +/- 3.9%, respectively; P < 0.05). Present
      results suggest that long-term changes in CBF depend on ischemic stroke subtype.
      Development of collateral circulation may occur after several years in
      atherothrombotic stroke patients. The findings raise doubts about the
      significance of chronic hemodynamic failure as a cause of stroke recurrence.

PMID- 8158221
TI  - Analysis of voltage-gated and synaptic conductances contributing to network
      excitability defects in the mutant mouse tottering.
AB  - 1. Intracellular current- and voltage-clamp recordings were carried out in CA3
      pyramidal neurons from hippocampal slices of adult tg/tg mice and their
      coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch
      clamp technique. The principal aim of this study was to investigate the
      mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant
      synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at
      depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network
      bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic
      voltage-dependent conductances underlying the mutant PDS prolongation, neurons
      were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or
      QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate
      (potassium channel blocker). The whole-cell currents active during the PDS showed
      a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg
      compared with +/+ cells, indicating that a defect in voltage-dependent
      conductances is unlikely to completely account for the mutant phenotype. 3. Bath
      application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30%
      reduction in PDS duration in both genotypes but failed to significantly alter the
      tg gene-linked prolongation compared with the wild type. These data indicate that
      the mutant PDS abnormality does not result from a selective increase of the N
      methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4.
      Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50
      microM) or bicuculline (1-5 microM) completely eliminated the difference in PDS
      duration between the genotypes. Furthermore, although both GABAA receptor
      antagonists increased the mean PDS duration in +/+ neurons, they did not
      significantly alter it in tg/tg neurons. These findings are consistent with a
      reduction in GABAA receptor-mediated synaptic inhibition during bursting in the
      tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal
      neurons were loaded intracellularly with chloride by the use of KCl-filled
      microelectrodes to examine the effect of reversing the hyperpolarizing chloride
      dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS.
      Chloride loading prolonged PDS duration in both genotypes, but the increase was
      greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory
      postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8158222
TI  - Response of commissural and other upper cervical ventral horn neurons to
      vestibular stimuli in vertical planes.
AB  - 1. To study their contribution to the vestibulocollic reflex, we have studied, in
      decerebrate paralyzed cats, the effect of sinusoidal vestibular stimulation in
      multiple vertical planes on the spontaneous activity of neurons in the C3 ventral
      horn. Antidromic microstimulation was used to identify 17/42 neurons as
      commissural; 10 of these were confirmed to have a projection to the contralateral
      ventral horn. 2. Dynamics of the responses of spontaneously firing neurons were
      studied with 0.05-1 Hz sinusoidal stimuli delivered near the plane of rotation
      that produced maximal modulation of neuron activity (response vector
      orientation). On the basis of their responses, we classified 38 neurons as
      receiving otolith, semicircular canal, or otolith + canal input. All three
      response types were found among commissure and nonantidromic neurons. 3. Two
      thirds of neuron response vector orientations pointed contralaterally. They were
      either near the anterior or posterior canal planes or in the roll quadrant. In
      the case of neurons with input from canals, the latter indicates convergence from
      the vertical canals on the same side. There were almost no vectors in the pitch
      quadrants. The distribution of response vector orientations resembles that seen
      in the vestibular nuclei and pontomedullary reticular formation, suggesting that
      commissural neurons may not make a new contribution to spatial processing in the
      vertical vestibulocollic reflex. 4. It is presumed that commissural neurons are
      premotor. If so, some have the properties to be in the pathway between the
      contralateral utricle and neck motoneurons. More generally, their actions could
      modify the effectiveness of vestibulospinal and reticulospinal fibers that have
      similar spatial properties and make synapses with neck motoneurons.

PMID- 8158223
TI  - Rhythmic modulation of the responsiveness of locust sensory local interneurons by
      walking pattern generating networks.
AB  - 1. Spiking local interneurons in the thoracic ganglia of the locust are known to
      process mechanosensory information from leg receptors and to contribute to
      postural reflexes. It is not clear, however, whether these interneurons are also
      involved in the control of leg movement during walking or whether their role in
      mediating local reflexes is phasically modulated by the walking pattern
      generating networks. To address these questions, intracellular recordings from
      spiking local interneurons in a midline population were made both in a "fictive
      walking" preparation reduced to isolated thoracic ganglia and in semi-intact
      locusts walking on a treadwheel. 2. In fictive walking (and therefore
      deafferented) preparations, rhythmic synaptic inputs were observed in 72% of the
      sampled local interneurons. These inputs resulted in a modulation of the
      interneurons' firing rate in phase with the centrally generated rhythm. A similar
      rhythmic drive was seen in spiking local interneurons recorded from semi-intact
      walking locusts. This drive persisted after amputation of the leg from which the
      interneurons received their sensory inputs. These results indicate that this
      population of interneurons receives inputs from central networks that participate
      in the generation of walking. 3. In fictive walking preparations where a hindleg
      was left attached to its segmental ganglion, individual local interneurons could
      be characterized physiologically by their receptive field properties. The central
      inputs were found to modulate the activity of members of all subclasses of
      interneurons (i.e., purely exteroceptive, purely proprioceptive, and with mixed
      receptive fields. The mode of modulation observed could oppose or assist the
      effect of sensory input expected to occur during normal walking.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8158224
TI  - Topographic patterns of responsiveness to odorants in the rat olfactory
      epithelium.
AB  - 1. Regional differences in odorant-induced responsiveness of the rat olfactory
      epithelium were measured via electrophysiological recordings [negative component
      of electro-olfactogram (Veog(-)) made from the surface of the olfactory
      epithelium on the nasal septum]. The nasal septum provided a flat surface from
      which multiple recordings could be made. 2. Veog(-)s were recorded from a
      standardized grid of 16 sites. This grid of recording sites extended over most of
      the surface of the olfactory epithelium on the nasal septum. 3. Twenty-one
      animals were tested for their responses to seven odorants. The animals were
      divided into three groups, each of which was tested with two different odorants
      plus amyl acetate, which provided a comparison between the groups. 4. For each
      odorant in each animal, topographic maps of relative responsiveness were derived
      to test whether odorants elicited different patterns of responses in the same
      individual. Topographic maps of responsiveness were derived also for the animal
      groups to test for the generality of the form of the maps for different odorants.
      Response latencies were also measured for each odorant at each recording site. 5.
      All individuals showed different topographic patterns of responses to the three
      test odorants. For most odorants, the location of the most responsive site was
      similar in all animals. In different animals the topographic maps for the same
      odorant were remarkably similar. Topographic maps for the odorants were all
      different from one another. 6. These results are consistent with the hypothesis
      that odorant quality is encoded in the differential spatial distribution of
      receptor cells whose differences in responsiveness appear to be distributed as a
      continuum across the epithelium. The results establish for a mammalian species
      what was previously reported in amphibians. These differences are presumed to be
      due to differential expression of odorant receptor proteins. 7. The mean response
      latency was 32 ms. This period was similar for all odorants, all animals, and all
      recording sites and was independent of Veog(-) amplitude. It is concluded that
      diffusion through the mucus contributed approximately 6 ms to the latency of
      onset of the responses to these odorants.

PMID- 8158225
TI  - Tactile activity in primate primary somatosensory cortex during active arm
      movements: correlation with receptive field properties.
AB  - 1. Five hundred ninety-five single neurons with tactile receptive fields (RFs) on
      the contralateral arm were isolated in the primary somatosensory cortex (SI) of
      awake, behaving monkeys. 2. Fifty-eight percent of the tactile cells showed
      significantly different levels of activity during active movements of the arm in
      eight directions or during active maintenance of the arm over the target
      endpoints. 3. The discharge of many of the active tactile cells was unimodally
      tuned with movement direction and the pattern of the tactile population activity
      varied in a meaningful fashion with arm movement direction and posture. 4. The
      intensity of the arm-movement-induced activity was typically less than that
      evoked by direct tactile stimulation of the cell's RF. 5. The probability of task
      related activity was correlated with certain RF properties, in particular the
      sensitivity of the cell to lateral stretch of the skin and to passive arm
      movements that avoided direct contact of the RF on any surface. 6. This suggests
      that task-related activity results mainly from the activation of tactile
      receptors by mechanical deformation of the skin as the arm changes geometry
      during movement. 7. These results demonstrate that tactile activity containing
      potential proprioceptive information is generated in SI during active arm
      movements that avoid direct contact of the skin with external surfaces. Whether
      or not this input contributes to the kinesthetic sensations evoked by the
      movements cannot be resolved by this study.

PMID- 8158226
TI  - Spontaneous firing patterns and axonal projections of single corticostriatal
      neurons in the rat medial agranular cortex.
AB  - 1. Spontaneous fluctuations of membrane potential, patterns of spontaneous
      firing, dendritic branching patterns, and intracortical and striatal axonal
      arborizations were compared for two types of corticostriatal neurons in the
      medial agranular cortex of urethan-anesthetized rats: 1) pyramidal tract (PT)
      cells identified by antidromic activation from the medullary pyramid and 2)
      crossed corticostriatal (CST) neurons identified by antidromic activation from
      the contralateral neostriatum. The ipsilateral corticostriatal projections of
      intracellularly stained PT neurons as well as contralateral corticostriatal
      neurons were confirmed after labeling by intracellular injection of biocytin. 2.
      All well-stained PT neurons had intracortical and intrastriatal collaterals. The
      more common type (6 of 8) was a large, deep layer V neuron that had an extensive
      intracortical axon arborization but a limited axon arborization in the
      neostriatum. The less common type of PT neuron (2 of 8) was a medium-sized,
      superficial layer V neuron that had a limited intracortical axon arborization but
      a larger and more dense intrastriatal axonal arborization. Both subclasses of PT
      neurons had anatomic and physiological properties associated with slow PT cells
      in cats and monkeys and conduction velocities < 10 m/s. All of the PT cells but
      one were regular spiking cells. The exception cell fired intrinsic bursts. 3.
      Intracellularly stained CST neurons were located in the superficial half of layer
      V and the deep part of layer III. Their layer I apical dendrites were few and
      sparsely branched. Their axons gave rise to an extensive arbor of local axon
      collaterals that distributed in the region of the parent neuron, frequently
      extending throughout the more superficial layers, including layer I. Axon
      collaterals were also traced to the corpus callosum, as expected from their
      contralateral projections, and they contributed axon collaterals to the
      ipsilateral neostriatum. In the neostriatum, these axons formed extended
      arborizations sparsely occupying a large volume of striatal tissue. All CST
      neurons were regular spiking cells. 4. Both types of cells displayed spontaneous
      membrane fluctuations consisting of a polarized state (-60 to -90 mV) that was
      interrupted by 0.1- to 3.0-s periods of depolarization (-55 to -45 mV)
      accompanied by action potentials. The membrane potential was relatively constant
      in each state, and transitions between the depolarized and hyperpolarized states
      were sometimes periodic with a frequency of 0.3-1.5 Hz. A much faster (30-45 Hz)
      subthreshold oscillation of the membrane potential was observed only in the
      depolarized state and triggered action potentials that locked to the depolarizing
      peaks of this rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8158227
TI  - Tactile activity in primate primary somatosensory cortex during active arm
      movements: cytoarchitectonic distribution.
AB  - 1. Cells were recorded in areas 3b and 1 of the primary somatosensory cortex (SI)
      of three monkeys during active arm movements. Successful reconstructions were
      made of 46 microelectrode penetrations, and 298 cells with tactile receptive
      fields (RFs) were located as to cytoarchitectonic area, lamina, or both. 2. Area
      3b contained a greater proportion of cells with slowly adapting responses to
      tactile stimuli and fewer cells with deep modality inputs than did area 1. Area
      3b also showed a greater level of movement-related modulation in tactile activity
      than area 1. Other cell properties were equally distributed in the two areas. 3.
      The distribution of cells with low-threshold tactile RFs that also responded to
      lateral stretch of the skin or to passive arm movements was skewed toward deeper
      laminae than for tactile cells that did not respond to those manipulations. 4.
      The variation of activity of tactile neurons during arm movements in different
      directions was weaker in the superficial laminae than in deeper cortical laminae.
      5. Cells with only increases in activity during arm movements were preferentially
      but not exclusively located in middle and superficial layers. Cells with
      reciprocal responses were found mainly in laminae III and V, whereas cells with
      only decreases in activity were concentrated in lamina V. 6. Overall, active arm
      movements evoke directionally tuned tactile and "deep" activity in areas 3b and
      1, in particular in the deeper cortical laminae that are the source of the
      descending output pathways from SI.

PMID- 8158228
TI  - Topographic representation of auditory space in the superior colliculus of adult
      ferrets after monaural deafening in infancy.
AB  - 1. We have investigated the role of monaural cues provided by the outer ear in
      the construction of a map of auditory space in the superior colliculus. Single
      unit recordings were made from the superior colliculus of adult ferrets that were
      deprived of binaural inputs by surgically ablating the ipsilateral cochlea on
      postnatal day 21 or 24. 2. The spatial response properties of auditory units in
      the deeper layers of this nucleus were studied using white-noise bursts presented
      under free-field conditions in an anechoic chamber. The thresholds of the units
      recorded in the monaural ferrets were not significantly different from those
      recorded in the superior colliculus of normal adult ferrets. In both groups the
      unit thresholds varied by 30-50 dB in each region of the superior colliculus. 3.
      In normal and monaural ferrets the elevation tuning tended to be sharper than the
      azimuth tuning. At sound levels of approximately 10 dB above threshold the
      auditory units recorded in both groups of animals were tuned to a specific region
      of space that was restricted in azimuth and elevation. The spatial location at
      which the maximum response was obtained (auditory best position) varied
      topographically in azimuth along the rostrocaudal axis of the nucleus and in
      elevation along the mediolateral axis. 4. The azimuthal distribution of best
      positions associated with each recording location in the superior colliculus of
      the monaural ferrets and the alignment between this dimension of the auditory map
      and that of the visual map in the overlying superficial layers were no different
      from those found at corresponding near-threshold sound levels in normal ferrets.
      5. Elevation spatial selectivity was examined in a smaller sample of units.
      Although elevation best positions shifted downward from the medial to the lateral
      side of the nucleus in both normal and monaural ferrets, we found that the
      topography of the auditory representation and its alignment with the visual
      representation were statistically different in the two groups of animals. 6.
      Increasing the sound level does not affect the representation of auditory space
      in normal ferrets. However, when the stimulus level presented to monoaural
      ferrets was increased, the receptive fields either expanded so that the responses
      were no longer tuned to any particular region of space, or the responses remained
      tuned but exhibited a marked shift in the value of the best position.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8158229
TI  - Autoactive peptides act at three distinct receptors to depolarize the bag cell
      neurons of Aplysia.
AB  - 1. In response to brief stimulation of an afferent input the bag cell neurons of
      Aplysia depolarize by 15-20 mV and generate an afterdischarge that, in vitro,
      lasts for approximately 30 min. During the discharge these neurons secrete three
      small peptides [bag cell peptides (BCPs)], Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu
      (alpha-BCP), Arg-Leu-Arg-Phe-His (beta-BCP), and Arg-Leu-Arg-Phe-Asp (gamma-BCP),
      that share a common core sequence and that have electrophysiological effects on
      the bag cell neurons themselves. We have now studied the action of these three
      peptides on bag cell neurons isolated in culture. All three peptides were found
      to be capable of producing a depolarization of these cells. 2. The ability of
      alpha-, beta-, and gamma-BCP to induce a depolarization in isolated bag cell
      neurons exhibits a seasonal variability. The response to the peptides is maximal
      from early summer through late fall and parallels the frequency of egg-laying in
      vivo. 3. The depolarization induced by alpha-, beta-, and gamma-BCP desensitizes
      with repeated application of peptide. Desensitization of the response to one
      peptide does not, however, prevent the response to application of one of the
      other two peptides. This suggests that separate autoreceptor populations exist
      for alpha-, beta-, and gamma-BCP. 4. As reported previously, desensitization of
      the depolarizing response to the peptides was also observed after preincubation
      of intact clusters of bag cell neurons with a high concentration of all three
      peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158230
TI  - Microstimulation of the medullary reticular formation during fictive locomotion.
AB  - 1. The present study was designed to determine the effects of microstimulation of
      the medullary reticular formation (MRF) on the locomotor activity of the cat in
      the absence of phasic afferent feedback from the limbs. To this end, both short
      (33 ms) and long (200 ms) trains of stimuli (trains of 0.2-ms pulses at 330 Hz,
      35 microA) were applied at 43 loci in the MRF (P:6-12 mm; L:0.5-1.5 mm), and in 3
      loci in the medial longitudinal fasciculus (P7.5, L < 0.5 mm) during fictive
      locomotion in the decerebrate and paralyzed cat. The locomotor pattern was
      monitored by recording the activity of representative flexor and extensor muscle
      nerves from each of the four limbs. 2. Short trains of stimuli evoked transient
      excitatory and/or inhibitory responses in extensor and flexor nerves of each limb
      that were incorporated into the locomotor pattern. In the majority of sites,
      excitatory responses were obtained in the motor nerves to both flexor and
      extensor muscles of the fore- and hindlimbs. The exception to this rule was the
      ipsilateral triceps, in which the predominant response was inhibitory. The
      amplitude of these responses was dependent on the time of the locomotor cycle at
      which the stimulus was delivered, and it was always maximum during the period of
      activity of the respective nerve. 3. The shortest latency response in the nerves
      to different muscles of the forelimb averaged between 5.6 and 7.3 ms; for the
      hindlimbs the values were between 6.9 and 9.3 ms. 4. Changing the depth at which
      the stimulation was applied in any one trajectory usually produced changes only
      in the amplitude of the evoked responses but occasionally also caused a change in
      the sign of these responses, especially in the most ventral regions of the MRF.
      5. At 72% of the loci (31/43), short trains of stimulation also changed the
      duration of the activity in the recorded nerves. These changes were often (20/31
      loci) sufficiently strong to alter the duration of the overall locomotor cycle.
      If one considers only the largest changes produced at each locus, stimulation
      during the period of ipsilateral extensor activity produced an average reduction
      in the ipsilateral locomotor cycle duration of 12.8 +/- 8.8% (mean +/- SD),
      whereas stimulation when the ipsilateral flexor nerve was active produced an
      average increase in locomotor cycle duration of 27.1 +/- 20.8%. 6. Long trains of
      stimuli produced similar but larger effects than the shorter trains and always
      reset the locomotor rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8158231
TI  - Neural interaction in cat primary auditory cortex II. Effects of sound
      stimulation.
AB  - 1. The effect of auditory stimulation with click trains, noise bursts, amplitude
      modulated noise bursts, and amplitude-modulated tone bursts on the correlation of
      firing of 1,290 neuron pairs recorded on one or two electrodes in primary
      auditory cortex of the cat was investigated. A distinction was made between
      neural synchrony (the correlation under stimulus conditions) and neural
      correlation (the correlation under spontaneous or under stimulus conditions after
      correction for stimulus-related correlations). For neural correlation 63% of the
      single-electrode pairs showed a unilateral excitation component, often combined
      with a common-input peak, and only 11% of the dual electrode pairs showed this
      unilateral excitation. 2. Under poststimulus conditions the incidence of
      correlograms with clear peaks was high for single-electrode pairs (80-90% range)
      and somewhat lower for dual-electrode pairs (50-60% range). The strength of the
      neural correlation for poststimulus conditions, from 0.5 to 2 s after a 1-s
      stimulus, was comparable with that obtained for 15-min continuous silence,
      suggesting that aftereffects of stimulation had largely disappeared after 0.5 s.
      A stationary analysis of the correlation coefficient corroborated this. 3. Two
      stimulus-correction procedures, one based on the shift predictor and the other
      based on the joint peristimulus-time histogram (JPSTH) were compared. The mean
      value of the neural correlation under stimulus conditions obtained after applying
      the poststimulus time (PST) predictor was on average 20% larger than the mean
      value obtained after application of the shift predictor; however, this was not
      significantly different at the 0.05 level. There were no differences in the shape
      of the correlograms. This suggests that the less time-consuming shift predictor
      based stimulus-correction procedure can be used for cortical neurons. 4. Under
      stimulus conditions neural correlation coefficients could be < or = 50% smaller
      than for spontaneous conditions. The strength of the stimulus-corrected neural
      correlation was inversely related to the relative size of the stimulus predictor
      (compared with the neural synchrony) and thus to the effectiveness of
      stimulation. This suggests that the assumption of additivity of stimulus and
      connectivity effects on neural synchrony is generally violated both for shift
      predictor and PST predictor procedures. 5. The neural correlogram peaks were
      narrower for single-electrode pairs than for dual-electrode pairs both under
      stimulus and spontaneous conditions. Under stimulus conditions the peaks were
      generally narrower than under spontaneous firing conditions.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8158232
TI  - Correlating resting discharge with small signal sensitivity and discharge
      variability in primary endings of cat soleus muscle spindles.
AB  - 1. In a previous report we proposed that primary endings of cat soleus muscle
      spindles can be separated into two kinds. One kind, called by us silent endings,
      at muscle lengths shorter than Lm -10 (maximum body length -10 mm), fell silent
      after a 5 mm shortening step. Spontaneous endings, on the other hand, were able
      to resume a resting discharge after a brief pause at all muscle lengths down to
      Lm -20. This report examines further differences between the two kinds of
      endings. 2. There were consistent differences in the muscle length dependence of
      the maintained level of resting discharge of the two kinds of endings, measured
      after a conditioning contraction or a contraction followed by a shortening step.
      The resting discharge of spindles with spontaneous endings, after both forms of
      conditioning increased progressively with length. For silent endings, after a
      conditioning contraction, resting discharge fell slightly at longer lengths. 3.
      Discharge variability, measured at a number of muscle lengths, showed a
      dependence both on mean interimpulse interval and on spindle type, being higher
      in silent than spontaneous spindles. 4. Small signal sensitivity was measured
      with the use of 1 Hz sinusoidal stretches applied longitudinally to the tendon.
      Sine wave amplitude was adjusted to give a 30% depth of modulation of the resting
      discharge. Spontaneous endings were consistently less sensitive to the stretches
      than silent endings at all muscle lengths. Average sensitivities, measured over a
      range of lengths between Lm -4 and Lm -20 mm were 0.30 imp.s-1.microns -1 for
      spontaneous endings and 0.66 imp.s-1.microns -1 for silent endings.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8158233
TI  - Potassium currents in mammalian and avian isolated type I semicircular canal hair
      cells.
AB  - 1. Type I vestibular hair cells were isolated from the cristae ampullares of the
      semicircular canals of the Mongolian gerbil (Meriones unguiculatus) and the white
      king pigeon (Columba livia). Dissociated type I cells were distinguished from
      type II hair cells by their neck to plate ratio (NPR) and their characteristic
      amphora shape. 2. The membrane properties of gerbil and pigeon type I hair cells
      were studied in whole-cell voltage- and current-clamp using the perforated patch
      technique with amphotericin B as the perforating agent. 3. In whole-cell current
      clamp, the average zero-current potential, Vz, measured for pigeon type I hair
      cells, was -70 +/- 7 (SD) mV (n = 18) and -71 +/- 11 mV (n = 83) for gerbil type
      I hair cells. 4. At Vz, for both gerbil and pigeon type I hair cells, a potassium
      current (IKI) was > or = 50% activated. This current deactivated rapidly when the
      membrane potential was hyperpolarized below -90 mV. 5. IKI was blocked by
      externally applied 4-aminopyridine (4-AP) (5 mM) and by internally applied 20 mM
      tetraethylammonium (TEA). It was also reduced when 4 mM barium was present in the
      external solution. The degree of block by barium increased as the membrane
      potential became more positive. External cesium (5 mM) blocked the inward
      component of IKI. When IKI was pharmacologically blocked, Vz depolarized by
      approximately 40 mV. Therefore IKI appears to be a delayed rectifier and to set
      the more negative Vz noted for isolated type I hair cells when compared to
      isolated type II hair cells, which do not have IKI. 6. A second, smaller
      potassium current was present at membrane potential depolarizations above -40 mV.
      This current was blocked by 30-50 mM, externally applied TEA, 100 microM
      quinidine, 100 nM apamin, but not 100 nM charybdotoxin, indicating that this is a
      calcium-activated potassium current, IK(Ca), different from the maxi-K calcium
      activated potassium current found in most other hair cells.

PMID- 8158234
TI  - Discrimination of direction of motion in human vision.
AB  - 1. Differences as low as 0.5 degrees can be discriminated in the direction of
      motion of a single spot of light moving with optimum speed and seen in the fovea
      for < 250 ms. There is no improvement for a cloud of random dots or a short line.
      2. For high velocities the thresholds approach those for the discrimination of
      orientation of a single line, when the length of the line is equal to the
      excursion of the dot and when the line is shown for the same duration. 3. The
      sensitivity for orientation of line of motion of a moving spot also shares two
      other attributes with that for the orientation of a single solid line of similar
      temporal and spatial extents: discrimination is seriously impaired when flanked
      by related close-by stimuli, and sensitivity is subject to simultaneous
      orientation contrast. 4. It is suggested that the orientation both of features
      and of lines of motion is processed by the same mechanism.

PMID- 8158235
TI  - Receptive-field maps of correlated discharge between pairs of neurons in the
      cat's visual cortex.
AB  - 1. To investigate the functional significance of temporally correlated discharge
      between nearby cells in the visual cortex, we obtained receptive-field maps of
      correlated discharge for 68 cell pairs in kittens and cats. Discharge from cell
      pairs was measured by a single extracellular electrode. A reverse correlation
      procedure was used to relate neural discharge to particular stimuli within a
      random sequence of briefly flashed bright and dark bars. Bicellular receptive
      fields (BRFs) were mapped by applying reverse correlation to approximately
      synchronous discharge from two cells. Unicellular receptive fields (URFs) were
      simultaneously mapped by separately applying reverse correlation to the discharge
      of each cell. 2. The receptive fields of the two neurons within each pair were
      initially studied by varying the orientation and spatial frequency of drifting
      sinusoidal gratings. After these tests a random sequence of appropriately
      oriented bars was used to evoke discharge suitable for reverse correlation
      analysis. For most cell pairs, the temporal pattern or strength of correlated
      discharge produced by such stimulation is different from that observed with
      stimulation by sinusoidal gratings. This indicates that visually evoked
      correlated discharge between nearby cells is stimulus dependent. 3. BRFs were
      classified according to their pattern of spatial sensitivity into three groups
      that roughly correspond to the single-cell receptive-field types of the lateral
      geniculate nucleus (LGN; center-surround) and visual cortex (simple and complex).
      These classifications were compared with the receptive-field types of the single
      cells within each pair. LGN-type and simple-type BRFs were only seen for pairs in
      which at least one of the cells was simple. Conversely, complex-type BRFs were
      only seen for pairs in which at least one of the cells was complex. 4. Because
      the reverse correlation procedure can be used to characterize the spatiotemporal
      receptive-field structure of simple cells, we were able to compare both the
      spatial and temporal properties associated with the URFs and BRFs of simple cell
      pairs. The spatiotemporal structure of the BRF of a simple-cell pair can largely
      be predicted on the basis of the two URFs. Although this prediction suggests the
      possibility that BRFs are stimulus artifacts, a shuffle procedure, in which
      multiple repetitions of random sequences were presented, verifies the neural
      origin of BRFs. BRFs emerge from specific neural pathways and are not simply a
      consequence of unicellular response preferences. 5. Five measures were derived
      from the reverse correlation analysis of simple-cell receptive fields: width,
      duration, optimal spatial and temporal frequency, and optimal velocity.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8158236
TI  - Length and width tuning of neurons in the cat's primary visual cortex.
AB  - 1. The classically defined receptive field of a visual neuron is the area of
      visual space over which the cell responds to visual stimuli. It is well
      established, however, that the discharge produced by an optimal stimulus can be
      modulated by the presence of additional stimuli that by themselves do not produce
      any response. This study examines inhibitory influences that originate from areas
      located outside of the classical (i.e., excitatory) receptive field. Previous
      work has shown that for some cells the response to a properly oriented bar of
      light becomes attenuated when the bar extends beyond the receptive field, a
      phenomenon known as end-inhibition (or length tuning). Analogously, it has been
      shown that increasing the number of cycles of a drifting grating stimulus may
      also inhibit the firing of some cells, an effect known as side-inhibition (or
      width tuning). Very little information is available, however, about the
      relationship between end- and side-inhibition. We have examined the spatial
      organization and tuning characteristics of these inhibitory effects by recording
      extracellularly from single neurons in the cat's striate cortex (Area 17). 2. For
      each cortical neuron, length and width tuning curves were obtained with the use
      of rectangular patches of drifting sinusoidal gratings that have variable length
      and width. Results from 82 cells show that the strengths of end- and side
      inhibition tend to be correlated. Most cells that exhibit clear end-inhibition
      also show a similar degree of side-inhibition. For these cells, the excitatory
      receptive field is surrounded on all sides by inhibitory zones. Some cells
      exhibit only end- or side-inhibition, but not both. Data for 28 binocular cells
      show that length and width tuning curves for the dominant and nondominant eyes
      tend to be closely matched. 3. We also measured tuning characteristics of end-
      and side-inhibition. To obtain these data, the excitatory receptive field was
      stimulated with a grating patch having optimal orientation, spatial frequency,
      and size, whereas the end- or side-inhibitory regions were stimulated with
      patches of gratings that had a variable parameter (such as orientation). Results
      show that end- and side-inhibition tend to be strongest at the orientation and
      spatial frequency that yield maximal excitation. However, orientation and spatial
      frequency tuning curves for inhibition are considerably broader than those for
      excitation, suggesting that inhibition is mediated by a pool of neurons.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8158237
TI  - Modulation of activity in dorsal root ganglion neurons by sympathetic activation
      in nerve-injured rats.
AB  - 1. Teased-fiber recordings were made from the axons of dorsal root ganglion (DRG)
      neurons in rats that underwent transection of the sciatic nerve 4-22 days
      previously. Many of the neurons had spontaneous ectopic discharge originating
      from within the DRG. 2. When postganglionic sympathetic efferents ending in the
      DRG were activated by tetanic stimulation of the T13 and L1 ventral roots (VRs),
      the ongoing afferent discharge was altered in more than one-half of the DRG
      neurons sampled. In most of the responsive units (62%), activity was augmented by
      this sympathetic stimulation; in the remainder (38%), activity was suppressed.
      Single-pulse stimuli of sympathetic efferents had no effect. 3. Responses to
      sympathetic stimulation began after a substantial delay (mean 14.3 s), peaked
      after 10-20 s, and then returned toward baseline over an additional 20-30 s. 4.
      Both excitatory and suppressive responses to sympathetic stimulation, as well as
      corresponding responses to systemically applied adrenaline, were blocked by the
      alpha-adrenoreceptor antagonist phentolamine. 5. Most of the active DRG neurons
      that responded to sympathetic stimulation, as well as others that did not, were
      excited by tetanic stimulation of neighboring afferent neurons that share the
      same DRG. These "crossed afterdischarge" responses were not blocked by
      phentolamine. Single-pulse stimuli of neighboring afferents had no effect. 6.
      Sympathetic-sensory coupling in DRGs of nerve-injured animals provides a
      previously unsuspected substrate for sympathetic involvement in neuropathic
      sensory dysfunction.

PMID- 8158238
TI  - An active membrane model of the cerebellar Purkinje cell II. Simulation of
      synaptic responses.
AB  - 1. Both excitatory and inhibitory postsynaptic channels were added to a
      previously described complex compartmental model of a cerebellar Purkinje cell to
      examine model responses to synaptic inputs. All model parameters remained as
      described previously, leaving maximum synaptic conductance as the only parameter
      that was tuned in the studies described in this paper. Under these conditions the
      model was capable of reproducing physiological recorded responses to each of the
      major types of synaptic input. 2. When excitatory synapses were activated on the
      smooth dendrites of the model, the model generated a complex dendritic Ca2+ spike
      similar to that generated by climbing fiber inputs. Examination of the model
      showed that activation of P-type Ca2+ channels in both the smooth and spiny
      dendrites augmented the depolarization during the complex spike and that Ca(2+)
      activated K+ channels in the same dendritic regions determined the duration of
      the spike. When these synapses were activated under simulated current-clamp
      conditions the model also generated the characteristic dual reversal potential of
      the complex spike. The shape of the dendritic complex spike could be altered by
      changing the maximum conductance of the climbing fiber synapse and thus the
      amount of Ca2+ entering the cell. 3. To explore the background simple spike
      firing properties of Purkinje cells in vivo we added excitatory "parallel fiber"
      synapses to the spiny dendritic branches of the model. Continuous asynchronous
      activation of these granule cell synapses resulted in the generation of
      spontaneous sodium spikes. However, very low asynchronous input frequencies
      produced a highly regular, very fast rhythm (80-120 Hz), whereas slightly higher
      input frequencies resulted in Purkinje cell bursting. Both types of activity are
      uncharacteristic of in vivo Purkinje cell recordings. 4. Inhibitory synapses of
      the sort presumably generated by stellate cells were also added to the dendritic
      tree. When asynchronous activation of these inhibitory synapses was combined with
      continuous asynchronous excitatory input the model generated somatic action
      potentials in a much more stochastic pattern typical of real Purkinje cells.
      Under these conditions simulated inter-spike interval distributions resembled
      those found in experimental recordings. Also, as with in vivo recordings, the
      model did not generate dendritic bursts. This was mainly due to inhibition that
      suppressed the generation of dendritic Ca2+ spikes. 5. In the presence of
      asynchronous inhibition, changes in the average frequency of excitatory inputs
      modulated background simple spike firing frequencies in the natural range of
      Purkinje cell firing frequencies (30-100 Hz). This modulation was very sensitive
      to small changes in the average frequency of excitatory inputs.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8158239
TI  - Activity induced elevations of intracellular calcium concentration in neurons of
      the deep cerebellar nuclei.
AB  - 1. Depolarization-induced changes in the cytosolic free calcium concentration
      ([Ca2+]i) were examined in slice-cultured neurons of the deep cerebellar nuclei
      by combined intracellular and multisite fura-2 recording techniques. 2. Firing of
      tetrodotoxin (TTX)-sensitive action potentials induced by depolarizing current
      pulses caused large elevations in somatic as well as proximal dendritic [Ca2+]i.
      In the dendrites, rise and decay times of [Ca2+]i were faster than in the soma.
      [Ca2+]i changes associated with depolarizations to < or = -40 mV in the presence
      of TTX were small compared with changes induced by Na+ spike firing, suggesting
      that Ca2+ influx through high voltage-activated Ca2+ channels is a major cause
      for Na+ spike-associated [Ca2+]i increases. 3. During sustained Na+ spike firing
      at a constant frequency (> 20 Hz), [Ca2+]i approached a constant level, after
      approximately 1 s in the dendrites and 2 s in the soma, respectively. The
      amplitude of the attained level was positively correlated with the firing
      frequency. We suggest that during tonic activity [Ca2+]i reaches a steady state
      determined by Ca2+ influx and extrusion. 4. TTX-resistant plateau potentials
      caused substantially greater [Ca2+]i increases in the dendrites than in the soma.
      In the dendrites, plateau-associated Ca2+ transients were comparable in amplitude
      to Ca2+ transients triggered by short (50 ms) Na+ spike trains, in the soma, they
      were considerably smaller. 5. Low-threshold spikes (LTSs) in association with a
      burst of Na+ spikes induced a sharp increase in [Ca2+]i both in the soma and in
      dendrites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158240
TI  - Cross-modal synthesis in the midbrain depends on input from cortex.
AB  - 1. The synthesis of information from different sensory modalities in the superior
      colliculus is an important precursor of attentive and orientation behavior. 2.
      This integration of multisensory information is critically dependent on inputs
      from a small area of association cortex, the anterior ectosylvian sulcus. Removal
      of these corticotectal influences can have a remarkably specific effect: it can
      eliminate multisensory integration in superior colliculus neurons while leaving
      their responses to unimodal cues intact. 3. Apparently, some of the associative
      functions of cortex are accomplished via its target neurons in the midbrain.

PMID- 8158241
TI  - Block of GABA-transaminase modifies GABAergic transmission at the crayfish
      synapses.
AB  - 1. The cytosolic concentration of a neurotransmitter is believed to be an
      important factor determining its release. The effects of ethanolamine-O-sulfate
      (EOS), a gamma-aminobutyric acid (GABA)-transaminase blocker, on GABAergic
      postsynaptic and presynaptic inhibitory neurotransmission were examined in the
      crayfish opener neuromuscular synapses. 2. Intracellular recordings of evoked
      excitatory (EPSPs) and inhibitory postsynaptic potentials (IPSPs) as well as
      loose macropatch clamp measurements of excitatory (EPSCs) and inhibitory
      postsynaptic currents (IPSCs) were used to evaluate the effects of the drug,
      which was applied exclusively to the nerve bundle. 3. Under normal conditions, a
      stimulus train to the inhibitor before the excitor stimulation elicited two
      phases of inhibition: 1) a large reduction in EPSP amplitude associated with a
      decrease in its time constant of decay (tau D) at time intervals of 0-15 ms and
      2) a moderate decrease in EPSP amplitude with a small change in EPSP tau D at
      intervals of 15-90 ms. EOS treatment selectively increased the inhibition of
      phase 2. 4. The muscle membrane electrical parameters and the existing
      postsynaptic tonic release of GABA were not affected by the drug. 5. EOS did not
      alter the IPSP's parameters such as amplitude, reversal potential, and
      conductance. 6. Quantal analysis of single IPSCs revealed no significant changes
      in the statistical parameters such as quantum size (q), quantal content (m),
      number of active zones (n), or probability of release (p). 7. Quantal analysis of
      EPSCs, released after interaction with the inhibitor, did exhibit a large
      reduction in m without any effect on q. 8. These results demonstrate that EOS has
      a specific and differential effect on neural transmission in two synapses of the
      same axon: it increases presynaptic inhibition without significant effect on the
      postsynaptic inhibitory mechanism.

PMID- 8158242
TI  - Neural encoding of single-formant stimuli in the cat. II. Responses of
      anteroventral cochlear nucleus units.
AB  - 1. We have studied responses of anteroventral cochlear nucleus (AVCN) units to
      single-formant stimuli (SFS), in an effort to make quantitative comparisons with
      responses observed in auditory-nerve fibers (ANFs) to the same stimuli (Wang and
      Sachs 1993) and to reveal some of the signal processing mechanisms at the AVCN.
      Single-unit recordings and subsequent analyses were performed on each type of
      commonly recorded units, namely primarylike (Pri), primarylike with notch (PN),
      sustained chopper (ChS), transient chopper (ChT), and onset chopper (OnC), as
      well as a few onset (On) units, from the AVCN in anesthetized cats. The responses
      were obtained at a wide range of sound levels and at a frequency range of 1-10
      kHz. Modulation in the envelopes of discharge patterns was quantified by a
      measure called modulation depth. 2. At moderate to high sound levels, most AVCN
      units were found to have enhanced modulation depth compared with that of ANFs,
      although the degree of enhancement varies among different types. All AVCN units,
      except Pri type, showed an enhancement in modulation depth over that of the
      highest of ANFs at moderate to high sound levels in the order of (from the
      highest to the lowest) On, OnC, ChT/PN, and ChS. Specifically, 1) modulation
      depth in Pri units was comparable to that of high spontaneous rate (SR) ANFs at
      low sound levels and to that of low/medium SR ANFs at high sound levels (in dB
      SPL). When sound level was normalized by unit threshold, Pri units, on average,
      exhibited only limited enhancement in envelope modulation at high sound levels (>
      80 dB re threshold); 2) PN units showed substantially enhanced modulation depth
      over that of all SR groups of ANFs at moderate to high sound levels in dB SPL or
      dB re threshold scales; 3) significant enhancement in modulation depth was seen
      in both ChS and ChT units, with a slightly higher modulation depth in ChT type
      across sound levels (in dB SPL or dB re threshold); 4) modulation depth of OnC
      units was higher than those of primary-like (Pri and PN) and chopper (ChS and
      ChT) units at a wide range of sound levels; 5) responses from a limited sample of
      On units showed the highest modulation depth among all types of AVCN units. 3.
      Detailed analysis revealed that the enhanced modulation depth in the responses of
      AVCN units is the result of increased envelope peak height and decreased envelope
      minimum, relative to those of ANFs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8158243
TI  - Adaptive plasticity of the auditory space map in the optic tectum of adult and
      baby barn owls in response to external ear modification.
AB  - 1. This study demonstrates the influence of experience on the establishment and
      maintenance of the auditory map of space in the optic tectum of the barn owl.
      Auditory experience was altered either by preventing the structures of the
      external ears (the facial ruff and preaural flaps) from appearing in baby barn
      owls (baby ruff-cut owls) or by removing these structures in adults (adult ruff
      cut owls). These structures shape the binaural cues used for localizing sounds in
      both the horizontal and vertical dimensions. 2. The acoustic effects of removing
      the external ear structures were measured using probe tube microphones placed in
      the ear canals. In both baby and adult ruff-cut owls, the spatial pattern of
      binaural localization cues was dramatically different from normal: interaural
      level difference (ILD) changed with azimuth instead of with elevation, the rate
      of change of ILD across space was decreased relative to normal, and the rate of
      change of interaural time difference (ITD) across frontal space was increased
      relative to normal. 3. The neurophysiological representations of ITD and ILD in
      the optic tectum were measured before and > or = 3 mo after ruff removal in
      adults and beginning at 4.5 months of age in baby ruff-cut owls. Multiunit tuning
      to ITD and to ILD was measured using dichotic stimulation in ketamine
      anesthetized owls. The tectal maps of ITD and ILD were reconstructed using visual
      receptive field location as a marker for recording site location in the optic
      tectum. 4. Adjustment of the tectal map of ITD to the altered spatial pattern of
      acoustic ITD was essentially complete in adults as well as in baby ruff-cut owls.
      This adjustment changed the magnification of ITD across the tectum, with
      resultant changes in ITD tuning at individual tectal sites of up to approximately
      25 microseconds (approximately 5% of the physiological range) relative to normal
      values. 5. Adaptation of the tectal ILD map to the ruff-cut spatial pattern of
      acoustic ILD was substantial but clearly incomplete in both adult and baby ruff
      cut owls. Although changes of up to approximately 15 dB (approximately 47% of the
      physiological range) relative to normal tuning were observed at certain tectal
      sites, the topography of the ILD map was always intermediate between normal and
      that predicted by the ruff-cut spatial pattern of acoustic ILD.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8158244
TI  - Neuronal activity in the caudolateral peribrachial pons: relationship to PGO
      waves and rapid eye movements.
AB  - 1. The present study was performed to examine the hypothesis that the
      caudolateral peribrachial area (C-PBL) may be directly involved in shifting the
      brain from the nonpontogeniculooccipital (non-PGO)-related states of waking (W)
      and slow-wave sleep (S) to the PGO-related states of slow-wave sleep with PGO
      waves (SP) and rapid eye movement (REM) sleep. 2. To test this hypothesis at the
      cellular level, we have recorded a sample of 226 spontaneously discharging units
      of the C-PBL during natural sleep-waking cycles in unanesthetized head-restrained
      cats and have correlated the action-potential data with the PGO waves. 3. Of
      these 226 cells, 67.26% (n = 152) were called PGO state-on units because they
      increased or began firing 15-5 s before the first PGO wave of SP and maintained
      their high firing rate throughout SP (31.30 +/- 6.0 Hz, mean +/- SD) and REM
      sleep (39.46 +/- 6.70 Hz); their firing rates in W (0.45 +/- 0.85) and S (0.70 +/
      1.26) were much lower. Among these PGO state-on neurons, 28.94% (n = 44)
      discharged high-frequency (> 500 Hz) spike bursts on the background of tonically
      increased firing rates during the PGO-related states. Contrastingly, 14.16% (n =
      32) of the cells (called PGO state-off units) fired tonically during W (11.54 +/-
      4.15) and S (9.43 +/- 3.87) but stopped or decreased firing 25-15 s before the
      first PGO wave of SP; their activity remained suppressed throughout SP (0.19 +/-
      0.44) and REM sleep (0.03 +/- 0.17). The remaining 18.58% (n = 42) cells fired (9
      10 Hz) tonically but were unrelated to the wake-sleeping cycle. 4. During SP and
      REM sleep, primary PGO waves were found to appear with equal frequency in each
      lateral geniculate body (LGB). During REM sleep these primary waves were
      ipsilateral to the direction of phasic rapid eye movements as previously reported
      by Nelson et al. (1983). 5. During SP and REM sleep PGO state-on burst cells
      fired high-frequency bursts on a background of tonic activity in association with
      each ipsilateral primary LGB PGO wave. The first spike of a burst preceded the
      beginning of the negative component of the ipsilateral LGB PGO waves by 25 +/-
      7.5 ms. On the basis of their sustained firing and the latency of their PGO
      related bursting, we call these neurons long-lead PGO-on burst-tonic
      cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8158246
TI  - Neural mechanisms underlying melodic perception and memory for pitch.
AB  - The neural correlates of music perception were studied by measuring cerebral
      blood flow (CBF) changes with positron emission tomography (PET). Twelve
      volunteers were scanned using the bolus water method under four separate
      conditions: (1) listening to a sequence of noise bursts, (2) listening to
      unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the
      same set of melodies, and (4) comparing the pitch of the first and last notes of
      the melodies. The latter two conditions were designed to investigate short-term
      pitch retention under low or high memory load, respectively. Subtraction of the
      obtained PET images, superimposed on matched MRI scans, provides anatomical
      localization of CBF changes associated with specific cognitive functions.
      Listening to melodies, relative to acoustically matched noise sequences, resulted
      in CBF increases in the right superior temporal and right occipital cortices.
      Pitch judgments of the first two notes of each melody, relative to passive
      listening to the same stimuli, resulted in right frontal-lobe activation.
      Analysis of the high memory load condition relative to passive listening revealed
      the participation of a number of cortical and subcortical regions, notably in the
      right frontal and right temporal lobes, as well as in parietal and insular
      cortex. Both pitch judgment conditions also revealed CBF decreases within the
      left primary auditory cortex. We conclude that specialized neural systems in the
      right superior temporal cortex participate in perceptual analysis of melodies;
      pitch comparisons are effected via a neural network that includes right
      prefrontal cortex, but active retention of pitch involves the interaction of
      right temporal and frontal cortices.

PMID- 8158245
TI  - Glutamate receptor agonists stimulate diverse calcium responses in different
      types of cultured rat cortical glial cells.
AB  - We examined the effects of different types of glutamate receptor agonists on the
      intracellular calcium concentration, ([Ca2+]i), in cultured rat cortical glial
      cells. The cells in these cultures were characterized immunocytochemically using
      antibodies against glial fibrillary acidic protein, A2B5, and OX-42. The
      metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-
      dicarboxylic acid produced Ca2+ mobilization from intracellular stores in all
      classes of cells. Agonists at non-NMDA glutamate receptors also produced large
      increases in [Ca2+]i, primarily in cells of the O-2A lineage. Disruption of
      intracellular Ca2+ stores with thapsigargin showed that increases in [Ca2+]i
      produced by activating AMPA/kainate receptors were primarily due to Ca2+ influx
      rather than Ca(2+)-induced Ca2+ release. Agonists at NMDA receptors were
      ineffective. Electrophysiological studies revealed that cells of the O-2A lineage
      exhibited moderate inward currents in response to kainate in Na(+)-containing
      solutions, but only small inward currents and outward rectification in Na(+)-free
      solutions. However, in the presence of cyclothiazide, the kainate-induced
      currents were increased in size and a rightward shift of the reversal potential
      with increased [Ca2+]o could be demonstrated. Activation of cells by kainate, but
      not by depolarizing stimuli, stimulated the uptake of Co2+. Polymerase chain
      reaction studies showed that the glutamate receptor subunits GluR1-4 and GluR6
      were all expressed in these cultures, but GluR5 was absent. The nature of the
      Ca2+ uptake pathway activated by non-NMDA receptor agonists in the O-2A lineage
      population is discussed. It is considered most likely that the O-2A lineage cells
      express both non-NMDA receptors that are relatively impermeable to divalent
      cations, as well as a smaller population that are Ca2+ permeable.

PMID- 8158247
TI  - Opioids mobilize calcium from inositol 1,4,5-trisphosphate-sensitive stores in
      NG108-15 cells.
AB  - Opioids elicit an increase in the intracellular free Ca2+ concentration ([Ca2+]i)
      in neuroblastoma x glioma hybrid NG108-15 cells, which, depending upon growth
      conditions, results from either Ca2+ influx in differentiated cells or Ca2+
      release from internal stores in undifferentiated cells (Jin et al., 1992). In
      this report we describe fura-2-based digital imaging studies that demonstrate
      that opioid-evoked Ca2+ release in these cells results from the activation of
      phospholipase C (PLC) and subsequent mobilization of the inositol 1,4,5
      trisphosphate (IP3)-sensitive store. D-Ala2-D-Leu5-enkephalin (DA-DLE) evoked
      concentration-dependent increases in [Ca2+]i (EC50 approximately equal to 4 nM).
      The response was blocked by naloxone (1 microM). In single cells, sequential
      application of selective opioid agonists (10 nM) evoked responses of the rank
      order DADLE = D-Pen2, D-Pen5-enkephalin (DPDPE) > trans-(+/-) 3,4-dichloro-N
      methyl-N-(2-[1- pyrrolidinyl]cyclohexyl) benzeneacetamide (U50488) > D-ala2, N-Me
      Phe4, Gly5-ol-enkephalin (DAMGO), consistent with activation of a delta-opioid
      receptor. Forty percent (n = 198) of the cells responded to 100 nM DADLE with a
      net [Ca2+]i increase of 483 +/- 40 nM. Bradykinin (100 nM) elicited a response in
      91% of the cells with a mean net amplitude of 707 +/- 36 nM. The DADLE-evoked
      responses were not blocked by removal of extracellular Ca2+; instead, they were
      abolished by treatment with 10 nM thapsigargin, an agent that depletes and
      prevents refilling of IP3-sensitive Ca2+ stores. A 1 microM concentration of
      U73122, an aminosteroid inhibitor of PLC, completely blocked the DADLE-evoked
      [Ca2+]i increase, while an inactive analog, U73433, was without effect. To
      explore the possible role of G-proteins in mediating opioid-induced [Ca2+]i
      increases in NG108-15 cells, we pretreated cells with pertussis or cholera toxin;
      pertussis toxin blocked the opioid-induced response while cholera toxin was
      without effect, consistent with a Gi- or Go-mediated effect. Activation of the
      opioid inhibitory pathway previously described for these cells appears to
      stimulate the phosphoinositide (PI) cascade as well. Including the PI cascade
      among the multiple second messenger systems modulated by opioids may be key to
      understanding the biochemical events that underlie acute and chronic opioid
      action.

PMID- 8158248
TI  - Axons regulate Schwann cell expression of the POU transcription factor SCIP.
AB  - SCIP (suppressed cAMP-inducible POU) is a POU domain transcription factor
      expressed by Schwann cells. Drugs that elevate intracellular cAMP, such as
      forskolin, increase the expression of SCIP and partially mimic the inductive
      effects of axons on Schwann cell gene expression. Thus, SCIP may be involved in a
      differentiation pathway in Schwann cells that is activated by axons. We have
      examined this issue by studying SCIP expression in developing, degenerating, and
      regenerating rat peripheral nerves, and in Schwann cell-neuron cocultures. High
      levels of SCIP mRNA were detected in developing and regenerating nerves, and
      axotomy at these times caused the level of SCIP mRNA to plummet. Similarly, there
      were many SCIP-immunoreactive Schwann cell nuclei in developing and regenerating
      nerves, and their number fell sharply after axotomy. SCIP-immunoreactive Schwann
      cells were associated with axons in developing and regenerating nerves, and in
      Schwann cell-neuron cocultures. These data demonstrate that axons upregulate the
      expression of SCIP in Schwann cells, and that SCIP is expressed in Schwann cells
      that ensheathe axons. Thus, SCIP may mediate some of the changes in Schwann cell
      gene expression that accompany axonal ensheathment.

PMID- 8158249
TI  - Mammalian homologs of Drosophila ELAV localized to a neuronal subset can bind in
      vitro to the 3' UTR of mRNA encoding the Id transcriptional repressor.
AB  - Mammalian cDNAs encoding a rat (Rel-N1) and a human (Hel-N1) neuronal RNA-binding
      protein have been cloned and characterized with respect to tissue specificity,
      neuroanatomical localization, and RNA binding specificity. Both proteins are
      highly similar to the product of the Drosophila elav gene, which is expressed in
      all neurons of the fly and is required for development of the nervous system.
      However, in situ hybridization of rat tissues demonstrated more restricted
      expression of Rel-N1 mRNA within a subset of neurons of the hippocampus, cortex,
      and other regions of the gray matter, but not in glial cells or white matter. In
      vitro RNA binding experiments demonstrated that Hel-N1 can bind to the 3'
      untranslated region (3' UTR) of Id mRNA, a transcript that encodes a helix-loop
      helix transcriptional repressor that is abundantly expressed in undifferentiated
      neural precursors. Sequences characterized for Hel-N1 binding were also
      abundantly present in the 3' UTR of the Drosophila extramacrochaetae mRNA, which
      encodes an Id homolog. Thus, we have identified a potential link between a
      neuronal 3' UTR RNA-binding protein and regulatory transcription factors involved
      in neural development. These findings are interpreted in light of recent studies
      in which mRNA 3' UTRs were found to be important for the regulation of cell
      growth and differentiation.

PMID- 8158250
TI  - Regulation of a periodic motor program in C. elegans.
AB  - A three-part motor program mediates a defecation every 45 sec in well-fed wild
      type Caenorhabditis elegans. Individual worms maintain this 45 sec rhythm with an
      SD of about 3 sec. We present evidence that the defecation cycle is controlled by
      an endogenous clock, most likely a neuronal pattern generator. The phase of the
      behavioral rhythm can be reset like pattern generators in other animals. The
      rhythm was reset by stimulating a well-characterized neuronal circuit mediating
      response to light touch. Also, animals that spontaneously stopped feeding
      interrupted their defecation rhythms. When they resumed feeding these animals
      reactivated the motor program in phase with the previously established rhythm,
      indicating that an endogenous clock continues to run even when the behavior is
      not expressed. Control of the defecation rhythm is independent of expression of
      the motor program. Most previously isolated mutations that affect the motor
      program (Thomas, 1990) do not alter the rhythm of the behavior; the motor steps
      themselves are defective but not the timing of their activation. Laser kills of
      identified motor neurons that affect particular parts of the motor program also
      did not change the defecation rhythm. Another sensory stimulus, food, strongly
      modulates defecation behavior: animals away from food rarely activated the motor
      program, and food dilution resulted in a graded lengthening of the cycle period.
      To elucidate further the relationship between feeding and defecation rhythms we
      studied a mutation, dec-8(sa200), that caused worms to continue to activate the
      motor program in the absence of food. The mutant did not require the presence of
      food to activate the motor program, although food made the rhythm more precise.
      In the presence of food, dec-8(sa200) animals exhibited tandem activations of the
      defecation motor program; the principal activation was followed by a more
      variable second activation. Further experiments suggested that the tandem
      activations of the motor program are not due to the activity of multiple
      oscillators.

PMID- 8158251
TI  - Neurosteroids modulate calcium currents in hippocampal CA1 neurons via a
      pertussis toxin-sensitive G-protein-coupled mechanism.
AB  - The inhibition of Ca2+ channel currents by endogenous brain steroids was examined
      in freshly dissociated pyramidal neurons from the adult guinea pig hippocampal
      CA1 region. The steady-state inhibition of the peak Ca2+ channel current evoked
      by depolarizing steps from -80 to -10 mV occurred in a concentration-dependent
      manner with the following IC50 values: pregnenolone sulfate (PES), 11 nM;
      pregnenolone (PE), 130 nM; and allotetrahydrocorticosterone (THCC), 298 nM. THCC,
      PE, and PES depressed a fraction of the Ca2+ channel current with a maximal
      inhibition of 60% of the total current. However, substitution of an acetate group
      for the sulfate group on PES resulted in a complete loss of activity.
      Progesterone had no effect (4% inhibition at 100 microM). Intracellular dialysis
      of PES had no effect on the Ca2+ current; concomitant extracellular perfusion of
      PES showed normal inhibitory activity, suggesting that the steroid binding site
      can only be accessed extracellularly. Analysis of tail currents at -80 mV
      demonstrated that THCC and PES slowed the rate of Ca2+ current activation and
      deactivation with no change in the voltage dependence of activation. Inhibition
      of the Ca2+ channel current by THCC and PES was voltage dependent. THCC primarily
      inhibits the omega-conotoxin (CgTX)-sensitive or N-type Ca2+ channel current. PE
      was nonselective in inhibiting both the CgTX- and the nifedipine (NIF)-sensitive
      Ca2+ channel current. These neurosteroids had no effect on the CgTX/NIF
      insensitive current. In neurons isolated from pertussis toxin (PTX)-treated
      animals by chronic intracerebroventricular infusion (1000 ng/24 hr for 48 hr),
      the Ca2+ channel current inhibition by PES, PE, and THCC was significantly
      diminished. Intracellular dialysis with GDP-beta-S (500 microM) also
      significantly diminished the neurosteroid inhibition of the Ca2+ channel current.
      Intracellular dialysis with the general kinase inhibitors H-7 (100 microM),
      staurosporine (400 nM), and a 20 amino acid protein kinase inhibitor (1 microM)
      also significantly prevented the THCC and PES inhibition of the Ca2+ channel
      current. Intracellular dialysis with the more specific inhibitors of protein
      kinase C (PKC), the pseudosubstrate inhibitor (PKCI 19-36) (1-2 microM) and
      bisindolylmaleimide (1 microM) significantly diminished the THCC and PE
      inhibition of the Ca2+ channel current. Rp- cAMP (100 microM), a specific
      inhibitor of cAMP-dependent protein kinase (PKA), had no effect on the THCC and
      PE inhibition of the Ca2+ current.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8158252
TI  - Self-administration of morphine, DAMGO, and DPDPE into the ventral tegmental area
      of rats.
AB  - Intracranial self-administration of mu- and delta-opioid agonists was
      demonstrated in male Long-Evans rats. Independent groups were allowed to lever
      press for ventral tegmental area (VTA) microinfusions of morphine, the selective
      mu agonist [D-Ala2,N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO), the selective delta
      agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE), or ineffective drug vehicle.
      Morphine, DAMGO, and DPDPE were each effective in establishing and maintaining
      lever-pressing habits. Lever-pressing responses were extinguished during a
      session when vehicle was substituted for drug, and reinstated when drug
      reinforcement was reestablished. Thus, it appears that VTA mu- and delta-opioid
      receptors are each involved in reinforcement of opiate self-administration. The
      effective dose of DAMGO--both for establishing and for maintaining the lever
      press habit--was 100 times lower than the effective doses for DPDPE and morphine,
      suggesting that the major contribution of VTA mechanisms to intravenous heroin
      self-administration involves an action on mu-opioid receptors.

PMID- 8158253
TI  - In the rat, endogenous nitric oxide modulates the response of the hypothalamic
      pituitary-adrenal axis to interleukin-1 beta, vasopressin, and oxytocin.
AB  - Nitric oxide (NO) synthase (NOS), the enzyme responsible for NO formation, is
      found in hypothalamic neurons containing oxytocin (OT), vasopressin (VP), and to
      a lesser extent corticotropin-releasing factor (CRF). Because NO is reported to
      modulate endocrine activity, we have investigated the hypothesis that endogenous
      NO participates in ACTH released by various secretagogues in the rat. In the
      adult male rat, the intravenous injection of interleukin-1 beta (IL-1 beta; 0.2
      0.3 micrograms/kg), VP (0.3-0.9 micrograms/kg), and OT (30 micrograms/kg)
      significantly increased plasma ACTH and corticosterone levels. Pretreatment with
      the L-form, but not the D-form, of N omega nitro-L-arginine-methylester (L-NAME;
      a specific inhibitor of NOS) markedly augmented the effects of these
      secretagogues whether it was injected acutely or over a 4 d period. Blockade of
      NOS activity also caused significant (P < 0.01) extensions of the duration of
      action of IL-1 beta, VP, and OT. In contrast, L-NAME did not significantly alter
      the stimulatory action of peripherally injected CRF, or centrally administered IL
      1 beta. Administration of L-arginine, but not D-arginine (100 mg/kg), used as a
      substrate for basal NO synthesis and which did not by itself alter the activity
      of the hypothalamic-pituitary-adrenal (HPA) axis, blunted IL-1-induced ACTH
      secretion, and reversed the interaction between L-NAME and IL-1 beta. The
      stimulatory action of endotoxin, a lipopolysaccharide that releases endogenous
      cytokines, was also augmented by inhibition of NO formation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8158254
TI  - A biphasic change in ribosomal conformation during transneuronal degeneration is
      altered by inhibition of mitochondrial, but not cytoplasmic protein synthesis.
AB  - Following loss of eighth nerve input, 20-40% of neurons in the neonatal chick
      cochlear nucleus, nucleus magnocellularis (NM), undergo cell death. Intracellular
      changes that precede the death of NM neurons include increased oxidative
      metabolism and mitochondrial volume, decreased cytoplasmic protein synthesis, and
      destruction of ribosomes. Six hours following afferent deprivation, dying NM
      neurons demonstrate complete loss of ribosomes and cessation of protein
      synthesis, suggesting that the rapid destruction of ribosomes leads to neuronal
      death. Increased NM neuron death occurs when mitochondrial upregulation is
      prevented by chloramphenicol, a mitochondrial protein synthesis inhibitor. This
      finding suggests that increased oxidative capacity is required for neuronal
      survival following loss of afferent input. To study changes in the ribosomes of
      afferent-deprived NM neurons, we obtained a monoclonal antibody to ribosomal RNA.
      This monoclonal antibody, Y10B, labels ribosomes of all NM neurons receiving
      normal synaptic activity. Following removal of afferent input, NM neurons
      demonstrate a biphasic change in their pattern of Y10B label. During the initial
      phase, there is a uniform decrease in the density of Y10B label. In the second
      phase, some NM neurons recover the capacity to bind the Y10B antibody while
      others remain unlabeled. During this second phase, NM neurons putatively destined
      to die, based on their failure to synthesize protein, are unlabeled by the Y10B
      antibody. New gene expression is not necessary to initiate the change in
      ribosomal immunoreactivity that leads deafferented NM neurons toward cell death.
      Blocking cytoplasmic protein synthesis with cycloheximide had no effect on the
      biphasic change in Y10B labeling of afferent-deprived NM neurons. Treating chicks
      with chloramphenicol, however, prevented the recovery of Y10B immunoreactivity in
      NM neurons during the second phase of the response to afferent deprivation.

PMID- 8158255
TI  - Cogeneration of neurons with a unique molecular phenotype in layers V and VI of
      widespread lateral neocortical areas in the rat.
AB  - Monoclonal antibody PC3.1 detects a unique subpopulation of neurons located
      mainly in layer VI and, to a lesser extent, in layer V within the lateral
      neocortical areas in the rat. In an attempt to characterize these neurons, we
      determined the time of their generation in selected neocortical areas by a double
      labeling experiment combining quantitative long-survival 3H-thymidine
      autoradiography and immunohistochemistry for the PC3.1 antigen. We found that the
      vast majority of PC3.1-positive neurons in both layers V and VI were generated
      concurrently at embryonic day 15 in all areas examined, demonstrating a strict
      correlation between the molecular identity of neurons and the time of their
      generation, irrespective of their final positions along the radial and tangential
      axes. In contrast, PC3.1-negative neurons, which should represent more diverse
      phenotypic identities, were generated during a more extended period of cortical
      development and tended to exhibit radial (inside-to-outside) and tangential
      (ventral-to-dorsal and rostral-to-caudal) neurogenetic gradients. Our findings
      indicate that laminar and tangential locations of cortical neurons are not
      established solely by a combination of mechanisms for the inside-out movement of
      newly generated neurons in each cortical area and for the broad tangential
      neurogenetic gradients. The results of this study suggest a distinct way of
      cortical development in which neurons with a common molecular phenotype are
      generated concurrently and migrate toward their eventual positions, which are not
      necessarily located in a single lamina. In addition, our results suggest some
      kind of tangential heterogeneity in the mechanism involved in neocortical
      histogenesis, supporting the concept of early regional specification within the
      neocortex.

PMID- 8158256
TI  - Regulation of neurotrophin receptor expression during embryonic and postnatal
      development.
AB  - Members of the NGF family of proteins act as neurotrophic agents for defined
      populations of peripheral and central neurons during embryonic and postnatal
      development. We have studied the presence of receptors for brain-derived
      neurotrophic factor (BDNF) and neurotrophin-3 and -4/5 (NT-3, NT-4/5) by cross
      linking radioiodinated neurotrophins to specific cell surface receptors. We have
      identified neurotrophin receptors representing full-length TrkB and TrkC and
      their truncated forms (lacking a functional cytoplasmic kinase domain) in
      neuronal as well as in non-neuronal tissues. During chicken embryonic and early
      postnatal brain development, expression of full-length TrkB and TrkC proteins
      preceded the onset of the truncated forms of these receptors. A similar pattern
      was also observed in mouse embryonic and early postnatal brain. The relative
      levels of neurotrophin receptors in the basal forebrain and in the hippocampus
      did not change significantly with age in mice. High levels of receptors for the
      three neurotrophins were detected in the nigrostriatal system. Full-length TrkB
      and TrkC receptors were found in chicken and rat embryonic ventral spinal cord,
      as well as on purified motoneurons. Again, truncated TrkB appeared significantly
      later than the full-length form on spinal motoneurons. In chicken embryonic
      retina and optic tectum we detected full-length TrkB and TrkC; however, the optic
      tectum also expressed large amounts of the truncated form of TrkB. TrkC but not
      TrkB was detected in chicken embryonic skeletal muscle, suggesting that NT-3 may
      have a novel function in this tissue. The presence of neurotrophin receptors in a
      wide variety of embryonic and postnatal tissues underlines the significant role
      of BDNF, NT-3, and NT-4/5 in embryonic and postnatal development. The regulation
      of the ratio of full-length versus truncated neurotrophin receptors may play an
      important role in the development, maturation, and maintenance of various
      neuronal networks.

PMID- 8158257
TI  - Magnocellular and parvocellular contributions to the responses of neurons in
      macaque striate cortex.
AB  - Anatomical and physiological studies of the primate visual system have suggested
      that the signals relayed by the magnocellular and parvocellular subdivisions of
      the LGN remain segregated in visual cortex. It has been suggested that this
      segregation may account for the known differences in visual function between the
      parietal and temporal cortical processing streams in extrastriate visual cortex.
      To test directly the hypothesis that the temporal stream of processing receives
      predominantly parvocellular signals, we recorded visual responses from the
      superficial layers of V1 (striate cortex), which give rise to the temporal
      stream, while selectively inactivating either the magnocellular or parvocellular
      subdivisions of the LGN. Inactivation of the parvocellular subdivision reduced
      neuronal responses in the superficial layers of V1, but the effects of
      magnocellular blocks were generally as pronounced or slightly stronger.
      Individual neurons were found to receive contributions from both pathways. We
      furthermore found no evidence that magnocellular contributions were restricted to
      either the cytochrome oxidase blobs or interblobs in V1. Instead, magnocellular
      signals made substantial contributions to responses throughout the superficial
      layers. Thus, the regions within V1 that constitute the early stages of the
      temporal processing stream do not appear to contain isolated parvocellular
      signals. These results argue against a direct mapping of the subcortical
      magnocellular and parvocellular pathways onto the parietal and temporal streams
      of processing in cortex.

PMID- 8158258
TI  - Responses in macaque visual area V4 following inactivation of the parvocellular
      and magnocellular LGN pathways.
AB  - A substantial body of evidence has suggested that signals transmitted through the
      magnocellular and parvocellular subdivisions of the LGN remain largely segregated
      in visual cortex. This hypothesis can be tested directly by selectively blocking
      transmission through either the magnocellular or parvocellular layers with small
      injections of lidocaine or GABA while recording cortical responses to a visual
      stimulus. In a previous study, we found that responses in the middle temporal
      visual area (MT) were almost always greatly reduced by blocks of magnocellular
      LGN, but that few MT neurons were affected by parvocellular blocks. In the
      present study, we have examined magnocellular and parvocellular contributions to
      area V4, which lies at the same level of processing in the cortical hierarchy as
      does MT and is thought to be a major recipient of parvocellular input. We found
      that inactivation of parvocellular layers usually resulted in a moderate
      reduction of visual responses (median reduction, 36%). However, comparable
      reductions in V4 responses were also seen following magnocellular blocks (median
      reduction, 47%). Directionally selective responses in V4 were not found to depend
      specifically on either subdivision. We conclude that area V4, unlike MT, receives
      strong input from both subdivisions of the LGN. These results suggest that the
      relationship between the subcortical magnocellular and parvocellular pathways and
      the parietal and temporal streams of processing in cortex is not one-to-one.

PMID- 8158259
TI  - Developmental changes in electrophysiological properties of LGNd neurons during
      reorganization of retinogeniculate connections.
AB  - Changes in electrophysiological properties of neurons in the ferret dorsal LGN
      (LGNd) were studied during early postnatal life, a critical developmental period
      when changes occur in morphology, connectivity, and response properties of LGNd
      neurons. Using the patch-clamp technique to obtain whole-cell recordings from
      cells maintained as in vitro slices of thalamus, several distinctive properties
      were observed in the immature LGNd. Relatively low resting membrane potentials
      were present that became more negative during the first 2 postnatal weeks. In
      addition, immature neurons exhibited high input resistances that decreased during
      early postnatal development. At all ages postnatally, neurons were capable of
      generating a train of Na(+)-dependent action potentials in response to
      intracellular injection of a depolarizing current pulse. Moreover, immature
      neurons resembled older cells in that little spike frequency adaptation was
      present during a train of action potentials. Action potential activity in
      immature neurons was nevertheless distinctive in several respects: (1) during the
      first 2-3 postnatal weeks action potentials became shorter in duration and larger
      in amplitude; (2) during the same period, thresholds for generation of action
      potentials changed in conjunction with the changes in resting membrane potential,
      becoming more negative; and (3) plots of frequency versus injected current
      revealed that thresholds for generation of trains of action potentials were
      reached with intracellular injection of lower current levels at earlier ages.
      These findings raise the possibility that relatively weak ionic currents
      generated at immature synapses have unexpectedly strong effects on the young LGNd
      neuron.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158260
TI  - A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease
      is involved in the regulation of neurite outgrowth.
AB  - The amyloid protein precursor (APP) of Alzheimer's disease is synthesized as an
      integral transmembrane protein that is released from cells in culture following
      proteolytic cleavage. The function of released APP is not known, although there
      is evidence that the protein may bind to components of the extracellular matrix
      (ECM). In the present study, substratum-bound APP stimulated neurite outgrowth in
      cultures of chick sympathetic and mouse hippocampal neurons. This effect was
      dependent upon the presence of substratum-bound heparan sulfate proteoglycans
      (HSPG). The effect of APP on neurite outgrowth was comparable to that of laminin.
      A 14 K N-terminal fragment of APP was found to bind heparin and a region close to
      the N-terminus of APP (residues 96-110) identified as a potential heparin-binding
      domain based on secondary structure predictions and molecular modeling.
      Mutagenesis of three basic residues (lysine-99, arginine-100, and arginine-102)
      resulted in a recombinant protein (APPhep) with decreased heparin-binding
      capacity. A peptide homologous to the heparin-binding domain was synthesized and
      found to bind strongly to heparin and to inhibit binding of 125I-labeled APP to
      heparin (IC50 approximately 10(-7) M). The peptide blocked the effect of APP on
      neurite outgrowth (IC50 approximately 10(-7) M), whereas two other peptides
      homologous to other domains in APP had no effect. The results indicate that the
      binding of APP to HSPG in the ECM may stimulate the effects of APP on neurite
      outgrowth.

PMID- 8158261
TI  - Effects of selective neonatal temporal lobe lesions on visual recognition memory
      in rhesus monkeys.
AB  - Ten-month-old infant monkeys that had received neonatal ablations of either
      inferior temporal cortex (area TE) or the medial temporal region were compared
      with age-matched normal infant monkeys in visual delayed nonmatching-to-sample
      with trial-unique objects. Both types of early damage caused impairment in visual
      recognition, but the degree of deficit after early area TE lesions differed
      sharply from that after early medial temporal removals. Thus, whereas early
      medial temporal damage yielded a marked decline in visual recognition when the
      delays and lists were gradually increased, early area TE damage yielded normal
      recognition up to a delay of 60 sec and only mild impairment at longer delays and
      lists. The data indicate that, unlike adult monkeys, which suffer severe and
      nearly equivalent losses in visual object recognition after both types of
      ablation, the infant monkeys' recognition ability is largely spared after early
      damage to area TE but not after early damage to the medial temporal lobe.
      Together with recent clinical reports of profound memory loss in children with
      early dysfunction of the medial temporal region, the present findings demonstrate
      that medial temporal lobe structures operate early to sustain visual recognition
      memory, and recovery from early damage is limited at best. Early damage to higher
      order visual cortex, however, can be largely compensated, presumably by one or
      more of the visual cortical areas that were left intact.

PMID- 8158262
TI  - Use-dependent growth of pyramidal neurons after neocortical damage.
AB  - Unilateral damage to the forelimb representation area of the sensorimotor cortex
      in adult rats increases dendritic arborization of layer V pyramidal neurons of
      the contralateral homotopic cortex. Arbor size was maximum at approximately 18 d
      postlesion, following which there was a partial elimination, or pruning, of
      dendritic processes. These neural changes were closely associated with behavioral
      events. The overgrowth of dendrites was related in time to disuse of the
      contralateral (to the lesion) forelimb and over-reliance on the ipsilateral
      forelimb for postural and exploratory movements. The pruning of dendrites was
      related to a return to more symmetrical use of the forelimbs. To investigate the
      possibility that lesion-induced asymmetries in motor behavior contributed to
      dendritic arborization changes, movements of the forelimb ipsilateral to the
      lesion were restricted during the period of dendritic overgrowth through the use
      of one-holed vests. This interfered with the increase in dendritic arborization.
      In contrast, animals that were allowed to use both forelimbs, or only the
      forelimb ipsilateral to the lesion, showed the expected increases. When sham
      operated rats were forced to use only one forelimb, no significant increases in
      arborization were found. Therefore, neither a lesion nor asymmetrical limb use
      alone could account for the dendritic overgrowth--it depended on a lesion
      behavior interaction. Furthermore, greater sensorimotor impairments were found
      when the dendritic growth was blocked, suggesting that the neural growth and/or
      associated limb-use behavior were related to functional recovery from the
      cortical damage. Finally, in a second experiment, immobilization of the impaired
      limb during the pruning period did not prevent the elimination of processes.
      Thus, the pruning of neural processes was not related simply to the recovery of
      more symmetrical forelimb use. There may be a period early after brain damage
      during which marked neural structural changes can occur in the presence of
      adequate behavioral demand.

PMID- 8158263
TI  - Dynamic behaviors of growth cones extending in the corpus callosum of living
      cortical brain slices observed with video microscopy.
AB  - During development, axons of the mammalian corpus callosum must navigate across
      the midline to establish connections with corresponding targets in the
      contralateral cerebral cortex. To gain insight into how growth cones of callosal
      axons respond to putative guidance cues along this CNS pathway, we have used time
      lapse video microscopy to observe dynamic behaviors of individual callosal growth
      cones extending in living brain slices from neonatal hamster sensorimotor cortex.
      Crystals of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate (Dil) were inserted into the cortex in
      vivo to label small populations of callosal axons and their growth cones.
      Subsequently, 400 microns brain slices that included the injection site, the
      corpus callosum, and the target cortex were placed in culture and viewed under
      low-light-level conditions with a silicon-intensified target (SIT) camera. Time
      lapse video observations revealed striking differences in growth cone behaviors
      in different regions of the callosal pathway. In the tract, which is defined as
      the region of the callosal pathway from the injection site to the corresponding
      target cortex, growth cones advanced rapidly, displaying continual lamellipodial
      shape changes and filopodial exploration. Forward advance was sometimes
      interrupted by brief pauses or retraction. Growth cones in the target cortex had
      almost uniform compact shapes that were consistently smaller than those in the
      tract. In cortex, axons adhered to straight radial trajectories and their growth
      cones extended at only half the speed of those in the tract. Growth cones in
      subtarget regions of the callosum beneath cortical targets displayed complex
      behaviors characterized by long pauses, extension of transitory branches, and
      repeated cycles of collapse, withdrawal, and resurgence. Video observations
      suggested that extension of axons into cortical targets could occur by
      interstitial branching from callosal axons rather than by turning behaviors of
      the primary growth cones. These results suggest the existence of guidance cues
      distinct for each of these callosal regions that elicit characteristic growth
      cone behaviors.

PMID- 8158264
TI  - Neural correlates of attentive selection for color or luminance in extrastriate
      area V4.
AB  - Rhesus monkeys were trained on a conditional orientation discrimination task in
      order to assess whether attentive selection for a color or luminance stimulus
      feature would affect visual processing in extrastriate area V4. The task required
      monkeys to select a bar stimulus based on its color or luminance and then to
      discriminate the angular tilt of the selected stimulus. The majority of neurons
      (74%) were selectively activated when the color or luminance of the stimulus in
      the receptive field matched the color or luminance of the cue. The activity was
      attenuated when there was not a match between the stimulus and the cue. The
      differential activation was based on the presence or absence of the stimulus
      feature and was independent of spatial location. Across the population of V4
      neurons, optimal stimuli that matched the selected color or luminance elicited
      about twice the activity as stimuli that did not match the selected feature. The
      feature-selective changes in activity were observed to develop beginning about
      200 msec after the stimulus onset and were maintained over the remainder of the
      behavioral trial. In this task the activity of V4 neurons reflected a selection
      based on the cued feature and not simply the physical color or luminance of the
      receptive field stimulus. Under these conditions, the topographic representation
      of the neural activity in area V4 highlights the potential targets in the visual
      scene at the expense of background objects. These observations offer a
      physiological counterpart to psychophysical studies suggesting that stimuli can
      be preferentially selected in parallel across the visual field on the basis of a
      unique color or luminance feature.

PMID- 8158265
TI  - Neural correlates of feature selective memory and pop-out in extrastriate area
      V4.
AB  - Neural activity in area V4 was examined to assess (1) whether the effects of
      attentive selection for stimulus features could be based on the memory of the
      feature, (2) whether dynamically changing the feature selection would cause
      activity associated with the newly selected stimuli to pop out, and (3) whether
      intrusion of more than one stimulus into the receptive field would disrupt the
      feature-selective activity. Rhesus monkeys were trained on several variations of
      a conditional orientation discrimination task. A differential activation of area
      V4 neurons was observed in the conditional discrimination task based on the
      presence of a match or a nonmatch between the conditional cue (a particular color
      or luminance) and the color or luminance of the receptive field stimulus. The
      differential activation was unchanged when the cue was removed and the animal had
      to remember its color (or luminance) to perform the task. When the cued feature
      was switched from one alternative to another in the middle of a trial the
      differential activation of neurons reversed over the course of 150-300 msec. If
      the stimulus in the receptive field contained the newly selected feature, V4
      neurons became activated without a concomitant change in the stimulus in
      classical receptive field. Across the topographic map of V4 the activity
      associated with the newly selected stimuli popped out, whereas the activity of
      deselected stimuli faded to the background levels of other background objects.
      Evidence of a suppressive input from stimuli outside the classical receptive
      field was clear in only 3 of 24 neurons examined. Intrusion into the classical
      receptive field by a second stimulus resulted in a diminished difference between
      matching and nonmatching conditions. These physiological data suggest a major
      role for attentional control in the parallel processing of simple feature
      selective differences.

PMID- 8158266
TI  - The distribution of GABAergic cells, fibers, and terminals in the monkey
      amygdaloid complex: an immunohistochemical and in situ hybridization study.
AB  - The primate amygdaloid complex is a prominent structure in the medial temporal
      lobe that comprises a variety of cytoarchitectonically distinct nuclei and
      cortical regions. The present study employed immunohistochemical and in situ
      hybridization techniques to determine the distribution of GABAergic cells,
      fibers, and terminals in the macaque monkey amygdala. Using a monoclonal antibody
      to GABA, immunoreactive neurons were observed throughout the amygdaloid complex
      (constituting approximately 20% of the neurons in the lateral nucleus), with
      higher densities located in the intercalated nuclei, amygdalohippocampal area,
      and posterior cortical nucleus. The lowest densities of labeled cells were
      observed in the central and medial nuclei. Interestingly, despite the low number
      of GABA-immunoreactive neurons, the terminal density in the central nucleus was
      among the highest in the amygdala. The GABAergic neurons in the amygdala were
      heterogeneous in morphology, and three general classes of immunopositive aspiny
      cells were observed. Using mRNA probes for glutamic acid decarboxylase (GAD:
      GAD65 and GAD67), in situ hybridization demonstrated distributions of labeled
      cells that generally replicated the immunohistochemical findings. One exception
      was in the central nucleus where, in contrast to the low number of
      immunohistochemically labeled cells, both GAD probes labeled large numbers of
      neurons. These studies on the organization of GABAergic circuits in the primate
      amygdala are significant because alterations of function in the human amygdala
      have been implicated in the pathogenesis of temporal lobe epilepsy and in the
      etiology of affective and other behavioral disorders. The present study provides
      baseline information with which to evaluate the role of GABAergic systems in
      amygdala-mediated behaviors and the potential contribution of GABAergic
      dysfunction in amygdala-associated disorders.

PMID- 8158267
TI  - Lamina-specific expression and activity-dependent regulation of seven GABAA
      receptor subunit mRNAs in monkey visual cortex.
AB  - Seven monkey-specific GABAA receptor subunit cDNAs were isolated and cloned;
      radioactive cDNA and cRNA probes derived from them were used for Northern blot
      analysis and in situ hybridization histochemistry of the primary visual cortex
      (area 17), with comparative observations on other cortical areas. cDNAs
      corresponding to alpha 1, alpha 2, alpha 4, alpha 5, beta 1, beta 2, and gamma 2
      GABAA receptor subunits were isolated and had sequences unique to the monkey but
      recognized mRNAs of distinct molecular weights consistent with those reported in
      other species. mRNAs for the alpha 1, beta 2, and gamma 2 subunits were expressed
      at much higher levels in area 17 than in motor, somatosensory, or temporal
      association cortex, possibly reflecting the greater density of GABA cells and
      synapses in area 17. In areas 17 and 18, each of the seven subunit mRNAs showed
      individually distinct patterns of laminar distribution. alpha 1, beta 2, and
      gamma 2 subunit mRNAs, which are thought to form the basis of receptors with the
      full range of classical GABAA receptor properties in the adult, were particularly
      enriched in layers II-III, IVC, and VI of area 17, following patterns of receptor
      distribution previously demonstrated by radioligand binding and
      immunocytochemistry. alpha 2, alpha 4, alpha 5, and beta 1 transcripts had quite
      different localization patterns that did not match the antoradiographic or
      immunocytochemical receptor localization patterns. alpha 2 and alpha 5 subunit
      mRNAs, which are thought to be the subunits mainly expressed in development, were
      enriched in layer VI and the underlying white matter, possibly reflecting the
      involvement of receptors formed from alpha 2 and alpha 5 polypeptides in trophic
      interactions in the cortical subplate zone during development of the cerebral
      cortex. Following 8-21 d periods of monocular deprivation induced by intravitreal
      injection of TTX, levels of alpha 1, beta 2, and gamma 2 subunit mRNAs were
      substantially reduced in deprived ocular dominance columns of layer IVC in area
      17. The effect was greatest for the alpha 1 subunit; for both alpha 1 and gamma 2
      subunit mRNAs, it extended into deprived rows of cytochrome oxidase-identified
      periodicities in other layers. Apart from the alpha 5 subunit mRNA, which showed
      reduced levels in layer VI, the other subunit mRNAs were unaffected by monocular
      deprivation. These results demonstrate the heterogeneity of GABAA receptor
      subunit expression in a complex, multilaminar cortical area. They suggest that
      receptors with different functional properties may be assembled from different
      combinations of subunit polypeptides in different layers and show that subunit
      expression is differentially regulated under activity-dependent conditions.

PMID- 8158268
TI  - Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and
      dopamine-dependent intracellular oxidative stress.
AB  - Methamphetamine (MA) produces selective degeneration of dopamine (DA) neuron
      terminals without cell body loss. While excitatory amino acids (EAAs) contribute
      to MA toxicity, terminal loss is not characteristic of excitotoxic lesions nor is
      excitotoxicity selective for DA fibers; rather, EAAs may modulate MA-induced DA
      turnover, suggesting that DA-dependent events play a key role in MA
      neurotoxicity. To examine this possibility, we used postnatal ventral midbrain DA
      neuron cultures maintained under continuous EAA blockade. As in vivo, MA caused
      neurite degeneration but minimal cell death. We found that MA is a vacuologenic
      weak base that induces swelling of endocytic compartments; MA also induces
      blebbing of the plasma membrane. However, these morphological changes occurred in
      MA-treated cultures lacking DA neurons. Therefore, while collapse of endosomal
      and lysosomal pH gradients and vacuolation may contribute to MA neurotoxicity,
      this does not explain selective DA terminal degeneration. Alternatively, MA could
      exert its neurotoxic effects by collapsing synaptic vesicle proton gradients and
      redistributing DA from synaptic vesicles to the cytoplasm. This could cause the
      formation of DA-derived free radicals and reactive metabolites. To test whether
      MA induces oxidative stress within living DA neurons, we used 2,7
      dichlorofluorescin diacetate (DCF), an indicator of intracellular hydroperoxide
      production. MA dramatically increased the number of DCF-labeled cells in ventral
      midbrain cultures, which contain about 30% DA neurons, but not in nucleus
      accumbens cultures, which do not contain DA neurons. In the DA neuron cultures,
      intracellular DDF labeling was localized to axonal varicosities, blebs, and
      endocytic organelles. These results suggest that MA redistributes DA from the
      reducing environment within synaptic vesicles to extravesicular oxidizing
      environments, thus generating oxygen radicals and reactive metabolites within DA
      neurons that may trigger selective DA terminal loss.

PMID- 8158269
TI  - Relationship of APP mRNA transcripts and levels of NGF and low-affinity NGF
      receptors to behavioral measures of age-related cognitive dysfunction.
AB  - This study was designed to examine the relationship between cognitive function
      and endogenous levels of NGF, low-affinity NGF receptor (LNGFR), and amyloid
      precursor protein (APP) mRNAs. Using 3 month (n = 5), 18 month (n = 40), and 29
      month (n = 17) Fischer-344 male rats, cognitive function was assessed with the
      Morris water maze, reverse transcription and polymerase chain reaction were used
      to quantify APP mRNAs, and NGF and LNGFR levels were determined with an ELISA.
      Cognitive function declined progressively with age from 3 months to 18 months,
      and from 18 months to 29 months, but only RNA content in the tissue declined
      significantly from 3 months to 18 months. Between 18 month and 29 month rats were
      small but statistically significant decreases only for Kunitz protease inhibitor
      (KPI)-inclusive mRNAs and cortical NGF levels. There was a small but
      statistically significant correlation between cognitive function and %KPI (the
      amount of KPI APP mRNAs relative to the total amount of APP mRNA), with lower
      %KPI related to more impaired spatial learning. No other statistically
      significant correlation or linear relationship could be detected between
      cognitive function and any of the other neurological measures or any combination
      of these measures (i.e., hippocampal levels of APP 695 mRNA, cortical and
      hippocampal levels of NGF, and cortical, hippocampal, and basal forebrain levels
      of LNGFR).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158270
TI  - Cloning and characterization of the choline acetyltransferase structural gene
      (cha-1) from C. elegans.
AB  - We have cloned the cha-1 gene from Caenorhabditis elegans using the method of
      transposon tagging, cha-1 is the structural gene for ChAT, the enzyme that
      synthesizes ACh. Sequence analysis of cDNAs predicts a protein of 71.5 kDa;
      comparison of the deduced amino acid sequence with ChAT sequences from other
      species confirms that cha-1 encodes ChAT. Comparison of cDNA and genomic
      sequences reveals that transcription is from right to left on the genetic map,
      and that some of the transcripts may result from trans-splicing of the 22-base
      spliced leader SL 1. The cha-1 gene is organized into 11 exons. The first exon
      contains only untranslated sequences, and is followed by an extremely long
      intron. The coding sequence of the cha-1 transcript is disrupted by mutations in
      the cha-1 gene. We have determined the sites of four transposon insertions and
      the end-points of two deletions that lead to the cha-1 mutant phenotype; one of
      the deletions appears to eliminate gene function completely. Comparison of the
      Drosophila, rat, and C. elegans genes reveals conserved motifs and conserved
      intron sites.

PMID- 8158271
TI  - Activated mutants of the alpha subunit of G(o) promote an increased number of
      neurites per cell.
AB  - The high concentration of the GTP-binding protein G(o) in the neuronal growth
      cone suggests that G(o) activation state may after neurite outgrowth. We find
      that activation of pertussis toxin-sensitive G-proteins by mastoparan increases
      neurite outgrowth from neuroblastoma cells. To examine G(o) activation
      specifically, point mutations homologous to activating, oncogenic mutations in
      alpha i2 and alpha s were introduced into the alpha subunit of G(o). The
      stability of the alpha o mutants to tryptic digestion confirms that they are
      activated. When expressed in PC12 or N1E-115 cells, activated alpha o doubles
      total neurites length per cell, primarily by increasing the number of neurites
      per cell. The growth cones of cells expressing activated alpha o are narrower
      than control growth cones. Expression of wildtype alpha o or the activated alpha
      subunits of other G-proteins did not affect total neurite length per cell. Thus,
      factors that lead to activation of G(o) can modulate neurite number per cell.

PMID- 8158272
TI  - Spatial correlates of firing patterns of single cells in the subiculum of the
      freely moving rat.
AB  - Hippocampal lesions cause spatial learning deficits, and single hippocampal cells
      show location-specific firing patterns, known as place fields. This suggests the
      hippocampus plays a critical role in navigation by providing an ongoing
      indication of the animal's momentary spatial location. One question that has
      received little attention is how this locational signal is used by downstream
      brain regions to orchestrate actual navigational behavior. As a first step, we
      have examined the spatial firing correlates of cells in the dorsal subiculum as
      rats navigate in an open-field, pellet-searching task. The subiculum is one of
      the few major output zones for the hippocampus, and it, in turn, projects to
      numerous other brain areas, each thought to be involved in various learning and
      memory functions. Most subicular cells showed a robust locational signal. The
      patterns observed were different from those in the hippocampus, however, in that
      cells tended to fire throughout much of the environment, but showed graded,
      location-related rate modulation, such that there were some localized regions of
      high firing and other regions with relatively low firing. There were slight
      quantitative differences between the proximal (adjacent to the hippocampus) and
      distal (farther from the hippocampus) subicular regions, with distal cells
      showing slightly higher average firing rates, spatial signaling, and firing field
      size. This was of interest since these two regions have different efferent
      connections. Examination of spike trains allowed classification of cells into
      bursting, nonbursting, and theta (putative interneuron) categories, and this is
      similar to subicular cell types identified in vitro. Interestingly, the bursting
      and nonbursting types did not differ detectably in spatial firing properties,
      suggesting that differences in intrinsic membrane properties do not necessitate
      differences in coding of environmental inputs. The results suggest that the
      subiculum transmits a robust, highly distributed spatial signal to each of its
      projection areas, and that this signal is transmitted in both a bursting and
      nonbursting mode.

PMID- 8158273
TI  - The developmental increase in ACh current densities on rat sympathetic neurons
      correlates with changes in nicotinic ACh receptor alpha-subunit gene expression
      and occurs independent of innervation.
AB  - Determining factors that control the expression of neurotransmitter receptors and
      the mechanisms by which these factors operate is essential to understand how
      synapses form during development and how receptor numbers change in the adult. In
      this study, we have investigated one such factor, the influence of innervation,
      on the developmental expression of nicotinic ACh receptors (nAChRs) on neonatal
      rat sympathetic neurons, both in terms of ACh current densities, and in terms of
      mRNA levels for the transcripts that encode these receptors. To date, nine genes
      have been cloned that encode neuronal nAChRs subunits in mammals. We demonstrate
      that mRNA encoding five nAChR subunits, alpha 3, alpha 5, alpha 7, beta 2, and
      beta 4, are present in neonatal rat sympathetic neurons. We show that mRNA levels
      for alpha 3 and alpha 7 subunits increase by more than threefold over the first 2
      postnatal weeks, a period when most synapses are forming on the neurons; however,
      we observed no significant change in mRNA levels for alpha 5, beta 2, or beta 4.
      Using whole-cell voltage-clamp techniques, we show that the increase in alpha
      subunit mRNA correlates with increases in ACh current densities, which double
      over the same period. To investigate the role of innervation, we cut the
      preganglionic nerve at birth and measured subunit mRNA levels and ACh current
      densities in denervated neurons 1-2 weeks later. Our results indicate that the
      preganglionic nerve differentially affects the mRNA level for the five nAChR
      transcripts, yet it has little influence on the developmental increase in ACh
      current densities.

PMID- 8158274
TI  - Antiinflammatory influences of alpha-MSH molecules: central neurogenic and
      peripheral actions.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH1-13) and its COOH-terminal
      tripeptide alpha-MSH11-13 (Lys Pro Val) inhibit inflammation when administered
      systemically. Recent evidence indicates that alpha-MSH1-13 can likewise inhibit
      inflammation in the skin solely via an action within the brain. Because of the
      potential importance of this discovery to understanding the control of
      inflammation and because alpha-MSH molecules might be useful for treatment of
      inflammation, experiments were performed to learn more about the mechanisms of
      action of these peptides. In tests on inflammation induced in the mouse ear by
      intradermal injections of recombinant human interleukin-1 beta, alpha-MSH1-1-13
      administered intracerebroventricularly effectively reduced inflammation. This
      effect of centrally administered alpha-MSH1-13 was inhibited by systemic
      injection of the nonspecific beta-adrenergic receptor blocker propranolol and by
      administration of a specific beta 2-adrenergic receptor antagonist; the effect
      was not altered by blockade of cholinergic, alpha-adrenergic, or beta 1
      adrenergic receptors. In mice with inflammation induced in a hind paw and with
      the spinal cord transected, the antiinflammatory effect of centrally administered
      alpha-MSH1-13 was prevented, indicating that intact descending neuronal pathways
      are required for the antiinflammatory influence of the central peptide. Systemic
      injection of alpha-MSH1-13 in animals with spinal cord transection had a smaller
      and later antiinflammatory effect, which suggests that the molecule also has an
      action, albeit lesser, in the periphery. However, alpha-MSH11-13 injected
      intraperitoneally had marked antiinflammatory activity in animals with spinal
      cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158275
TI  - GABAA receptor subunit immunoreactivity in primate visual cortex: distribution in
      macaques and humans and regulation by visual input in adulthood.
AB  - Subunit proteins that make up functional GABAA receptors were localized
      immunocytochemistry in the primary visual cortex (area 17) of adult monkeys and
      humans. Immunoreactivity for the alpha 1, beta 2/3, and gamma 2 subunits is
      greatest in layers (II-III, IVA and IVC) of monkey area 17 that contain the
      highest density of GABA neurons and terminals. Immunostaining for each subunit is
      unevenly distributed in layers II and III, where patches of immunoreactivity
      correspond to regions of intense cytochrome oxidase (CO) staining, and in layer
      IVA, where intense immunoreactivity forms a honeycomb pattern identical to the CO
      staining pattern. Immunoreactivity for the subunits is localized principally
      within the neuropil, which, by simultaneous comparison with the distribution of
      microtubule-associated protein immunostaining, was found to include bundles of
      thin dendrites and zones of numerous dendritic segments. In addition, gamma 2
      immunostaining surrounds the somata of a subpopulation of GABAergic neurons,
      immunoreactive for the calcium-binding protein parvalbumin. All three subunits
      are present in the somata and processes of neurons that occupy the white matter
      subjacent to monkey area 17. In human visual cortex, the alpha 1, beta 2/3, and
      gamma 2 subunits are distributed in a manner similar to that found in monkeys,
      with relatively intense immunostaining in layers IVC and IVA. In layer IVC,
      vertical stripes of intense receptor immunostaining (20-30 microns wide)
      alternate with wider stripes of pale immunostaining (30-60 microns wide). In the
      upper and lower halves of IVC beta, these stripes form lattices similar to those
      in layers IVC and IVA of monkeys. Following monocular deprivation by intravitreal
      injections of TTX in adult monkeys, immunoreactivity for each subunit in layer
      IVC consists of alternating intensely and lightly stained stripes. Comparison
      with the pattern of CO staining indicates that intense immunostaining for alpha
      1, beta 2/3, and gamma 2 occurs in normal-eye stripes while abnormally light
      immunostaining is present in deprived-eye stripes. For all three subunits,
      immunoreactivity in deprived-eye stripes is reduced within 5 d of monocular
      deprivation and remains abnormally low for deprivations that extend to at least
      30 d. These findings indicate that each of several GABAA receptor subunits adopt
      similar laminar and compartmental distributions in monkey and human area 17 and
      are likely to be expressed by the same neurons. The deprivation-dependent
      reduction in immunoreactivity for alpha 1, beta 2/3, and gamma 2 subunits
      suggests that all are regulated by visually driven activity.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8158276
TI  - Direct observation of the effect of autoreceptors on stimulated release of
      catecholamines from adrenal cells.
AB  - The direct effect of alpha 2-autoreceptors was studied by measuring the effects
      of piperoxan, an alpha 2-autoreceptor antagonist, and clonidine, an agonist on
      catecholamine exocytosis, from single bovine chromaffin cells in culture.
      Catecholamine release was elicited by stimulation with 100 microM nicotine and
      was monitored electrochemically with a carbon-fiber microelectrode placed
      adjacent to the cell. These electrodes allowed the number of exocytotic release
      events to be monitored and reported as total charge for release following a
      specific stimulus. Repeated stimulation with 100 microM nicotine showed that
      total release caused by the second exposure to nicotine was 32% of the first, and
      release caused by the third exposure to nicotine was 80% of the second. Total
      release of catecholamine increased significantly after application of 20 microM
      piperoxan relative to a control application of balanced salt solution.
      Application of 20 microM piperoxan alone did not cause release. After the cells
      were incubated in culture medium containing 20 microM clonidine, a significant
      decrease in nicotine-stimulated catecholamine release was observed. These results
      confirm that there are autoreceptors on chromaffin cells and, when relatively
      high levels of catecholamine are released, the catecholamine stimulates the alpha
      2-autoreceptors, which inhibits subsequent release through a negative feedback
      mechanism. In addition to piperoxan, the sympathomimetic drug amphetamine also
      increases quantal release after application of nicotine. Amphetamine increases
      the extracellular concentration of catecholamine, and these data appear to
      indicate that at least part of the pharmacology of amphetamine might involve
      blocking catecholamine autoreceptors.

PMID- 8158277
TI  - Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different
      neurons of rat brain.
AB  - In the nervous system, a wide diversity of K+ channels are formed by the
      oligomeric assembly of subunits encoded by a large number of K+ channel genes.
      The physiological functions of a specific K+ channel subunit in vivo will be
      dictated in part by its subcellular location within neurons. We have used a
      combined in situ hybridization and immunocytochemical approach to determine the
      subcellular distribution of Kv1.2, a member of the Shaker subfamily of K+ channel
      genes. In contrast to other characterized K+ channel subunits, Kv1.2 protein
      shows a complex differential subcellular distribution in neurons of rat brain. In
      some of these neurons (e.g., hippocampal and cortical pyramidal cells, and
      Purkinje cells), Kv1.2 is concentrated in dendrites, while in others (e.g.,
      cerebellar basket cells), Kv 1.2 is predominantly, if not exclusively, localized
      to nerve terminals. Furthermore, Kv1.2 immunoreactivity was also detected in
      certain axon tracts. We hypothesize that the differential sorting of Kv1.2 could
      result from association of Kv1.2 with varying heterologous K+ channel subunits in
      different cell types, with the implication that Kv1.2 may participate in distinct
      heteromultimeric K+ channels in different subcellular domains. The findings
      suggest that Kv1.2-containing K+ channels may play diverse functional roles in
      several neuronal compartments, regulating presynaptic or postsynaptic membrane
      excitability, depending on the neuronal cell type.

PMID- 8158278
TI  - Component placement optimization in the brain.
AB  - This computational neuroanatomy study evaluates how well some formalisms derived
      from combinatorial network optimization theory fit as models for brain structure.
      At multiple hierarchical levels--brain, ganglion, individual cell--physical
      placement of neural components appears consistent with a single, simple goal:
      minimize cost of connections among the components. The most dramatic instance of
      this "save wire" organizing principle is reported for adjacencies among ganglia
      in the nematode nervous system; among about 40,000,000 alternative layout
      orderings, the actual ganglion placement in fact requires the least total
      connection length. In addition, evidence supports a component placement
      optimization hypothesis for positioning of individual neurons in the nematode,
      and also for positioning of mammalian cortical areas.

PMID- 8158279
TI  - A slow excitatory postsynaptic potential mediated by 5-HT2 receptors in nucleus
      prepositus hypoglossi.
AB  - Intracellular recordings were made from neurons of the nucleus prepositus
      hypoglossi in slices of guinea pig medulla. 5-HT (serotonin) caused a
      hyperpolarization followed by a late depolarization. The hyperpolarization was
      mediated by 5-HT1A receptor activation and could be selectively blocked by
      pindobind-5HT1A (PBD). 5-HT then caused a depolarization only. A selective 5-HT2
      agonist, (+)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), also caused a
      depolarization. Ketanserin and spiperone, 5-HT2 antagonists, blocked the
      depolarization due to both 5-HT and DOI. Focal electrical stimulation caused an
      IPSP mediated by 5-HT acting upon 5-HT1A receptors and a slow EPSP (s-EPSP). PBD
      blocked the IPSP, leaving an isolated s-EPSP. Both spiperone and ketanserin
      antagonized the s-EPSP, while DOI occluded it. The s-EPSP was from 2 to 10 mV in
      amplitude and 35-50 sec in duration, and showed voltage dependence consistent
      with a decrease in potassium conductance. Both the IPSP and the s-EPSP were
      presynaptically inhibited by the 5-HT1D agonist sumatriptan. These data indicate
      that the s-EPSP is mediated by 5-HT acting upon 5-HT2 receptors. This represents
      strong support for the role of 5-HT as an excitatory neurotransmitter in the CNS.
      Further, it demonstrates that synaptic release of 5-HT can mediate opposing
      effects on the membrane potential of a single cell.

PMID- 8158280
TI  - Distributed input to the tail-siphon withdrawal circuit in Aplysia from neurons
      in the J cluster of the cerebral ganglion.
AB  - Plasticity in the circuits for the withdrawal reflexes has been correlated with
      several simple forms of nonassociative and associative learning in Aplysia, and
      biochemical, biophysical, and molecular mechanisms of plasticity in these
      circuits have been described. In order to examine network features of this
      plasticity, we identified and characterized a component of the modulatory
      circuitry for the tail-siphon withdrawal circuit. Activation of mechanoafferent
      neurons in the J cluster of the cerebral ganglion produced strong and distributed
      input to the tail-siphon withdrawal circuit. Stimulation of the J cells led to
      excitatory and inhibitory effects in the sensory neurons in the pleural ganglion,
      the tail motor neurons in the pedal ganglion, and several classes of interneurons
      in the pleural ganglion, including the multifunctional neuron LPI17. Activation
      of the J cells produced both fast and slow post-synaptic potentials in neurons of
      the tail-siphon withdrawal circuit. Of particular interest was the ability of the
      J cells to produce slow EPSPs in the pleural sensory neurons. These slow EPSPs
      were associated with an increase in the excitability of the sensory neurons, but
      no effect of the J cells on spike duration in the sensory neurons was observed.
      The J cells appear to mediate both sensory and modulatory inputs to the circuit
      for tail withdrawal.

PMID- 8158281
TI  - The use of Weibull statistics in mechanical testing of brittle dental materials.
AB  - The mean strength that has traditionally been taken as a measurement of the
      strength of a material does not reflect the true strength, and therefore it
      cannot be used as a design parameter. This explains why many brittle materials
      fail at unpredictable stress, either below or above the mean strength. By using
      Weibull statistics, the prediction and assessment of strength can be made more
      sensibly. The performance of a material can be predicted by considering a stress
      at a lower level of failure probability.

PMID- 8158282
TI  - beta 2-Microglobulin levels in serum and saliva of patients with juvenile
      periodontitis.
AB  - beta 2-Microglobulin (beta 2-m) is a low-molecular-weight protein which has been
      suggested to play an important role in immune functions. The aim of this study
      was to determine beta 2-m levels in serum and saliva from patients with juvenile
      periodontitis (JP) and to compare them with those of periodontally healthy
      subjects. The study was performed on 11 patients with JP and 10 periodontally
      healthy controls (C). Clinical measurements were recorded and serum and saliva
      samples were obtained from the individuals. beta 2-m levels were determined using
      the ELISA technique. Serum beta 2-m levels were significantly higher in the JP
      group than in the control group. In saliva, no significant difference in beta 2-m
      levels between the groups was found. The higher beta 2-m levels in serum in the
      JP group suggest that beta 2-m may play a role as a systemic factor in the
      etiology and pathogenesis of JP.

PMID- 8158283
TI  - Myeloperoxidase activity in peripheral blood, neutrophil crevicular fluid and
      whole saliva of patients with periodontal disease.
AB  - Mean levels of myeloperoxidase (MPO) activity were determined in samples of
      gingival crevicular fluid (GCF), whole saliva and peripheral blood neutrophils
      from patients with rapidly progressive periodontitis (RPP) and adult
      periodontitis (AP) using a spectrophotometric method. The mean neutrophil MPO
      activity in the RPP group was 563.1 +/- 137.05 U/l x 10(6)/ml, that in the AP
      group was 483.3 +/- 88.81 U/l x 10(6)/ml, and that in the control group was 220.6
      +/- 26.7 U/l x 10(6)/ml. The mean GCF MPO activity in the RPP group was 15.13 +/-
      2.34 U/mg, which was significantly higher than in the other two groups. The mean
      whole saliva MPO activity in the RPP group was 0.14 +/- 0.04 U/ml, that in the AP
      group was 0.11 +/- 0.02 U/ml, and that in the control group was 0.05 +/- 0.06
      U/ml. MPO activity detected in the samples was significantly increased in the
      patient groups when compared to the healthy subjects. The highest MPO activity
      was found in the RPP group. The present findings suggest a relationship between
      MPO activity and the pattern and severity of periodontal breakdown. Also the
      increased MPO activity in periodontally diseased patients can be attributed to
      the increased number of neutrophils, the degranulation of these cells and also
      their hyperactive state in the presence of chronic antigenic stimulation.

PMID- 8158284
TI  - Natural antibody against Thomsen-Friedenreich antigen in sera of patients with
      carcinomas and infectious diseases.
AB  - The levels of natural antibody against Thomsen-Friedenreich (TF) antigen in sera
      of patients with various cancers and infectious diseases were examined by an
      enzyme-linked immunosorbent assay (ELISA) and compared with those of healthy
      donors. The levels of antibody against TF antigen in sera of patients with
      adenocarcinomas such as gastric, pancreatic and colorectal cancers were lower
      than those of patients with hepatoma, pyelonephritis and pneumonia. These
      findings may reflect the expression of TF-antigen in adenocarcinoma tissues.

PMID- 8158285
TI  - Basic studies of radiopaque resin monomer (III). Physical properties of trial
      composite resins.
AB  - A series of studies has been conducted on the synthesis of radiopaque monomers
      and the development of a composite resin having these monomers. Using
      octachlorocyclotetraphosphazene, P4N4Cl8 (4PNC), three kinds of radiopaque
      cyclophosphazene monomers, 4PN(Br3Ph)1-3-(EMA)7-5, were synthesized by reacting 1
      3 mols of tribromophenol (Br3Ph) and 7-5 mols of 2-hydroxyethyl methacrylate
      (HEMA). As the monomer for an organic composite filler, 70% (wt) synthesized
      monomer was used with silica (OX-50) treated with silane mixed at 30% and ground
      after heat-polymerization and then run through a 325-mesh sieve after
      polymerization. As a base monomer, 25% urethane monomer (U-2TH) was mixed in 25%
      synthesized monomer and photosensitizer was added. The composite resin was
      prepared by mixing 50% organic composite filler with 50% base monomer, and
      polymerized with a Dentacolor XS (Kulzer) visible light-curing apparatus by
      irradiation for 90 s on each side, 180 s in total. Mechanical properties did not
      vary with the increase in the number of tribromophenol replacements. Compressive
      yield strength was more than 120 MPa in all cases. Transverse strength was 60-75
      MPa and hardness was HK 26-30. However, the aluminum equivalent increased with
      the increase in the number of tribromophenol replacements. In the case of 4PN
      (Br3Ph)3, the value was 8.8 mm, whereas in the case of commercial composite
      resin, it was 0.4-10.4 mm.

PMID- 8158286
TI  - Thermal properties of glass ionomer cement.
AB  - Five currently available glass ionomer cements (BASE CEMENT, DENTIN CEMENT, HY
      BOND GLAS IONOMER-F, KETAC CEM, TOKUSO IONOMER) were studied with regard to the
      relationship between thermal properties and powder-liquid ratio (P/L ratio). The
      experiments were performed using five different P/L ratio of 0.8, 0.9, 1.0, 1.1
      and 1.2 (P/L = 1.0: manufacturer's instruction) and measured with a xenon flash
      thermal-constant measuring device. Thermal diffusivity of the glass ionomer
      cements ranged from 0.212 to 0.303 x 10(-2) cm2 s-1; it increased according to
      the increase in the P/L ratio. The specific thermal capacity of the glass ionomer
      cements ranged from 1.011 to 1.369 Jg-1 K-1; it decreased with the increase in
      the P/L ratio. Thermal conductivity of the glass ionomer cements ranged from
      0.505 to 0.712 Wm-1 K-1; it increased according to the increase in the P/L ratio.

PMID- 8158287
TI  - Characteristics of a 28-kDa collagenous protein extracted with guanidine from
      EDTA-demineralized rabbit alveolar bone.
AB  - Bone proteins in alveolar bone of mandibles from young adult rabbits (3-month
      old) were extracted with 4.0 M guanidine hydrochloride (GuHCl), followed by 0.5 M
      ethylenediaminetetraacetate, and again with 4.0 M GuHCl (G2-ext). The proteins in
      the G2-ext were fractionated on a gel-filtration column, followed by an anion
      exchange column in the presence of 7.0 M urea. A 28-kDa protein was isolated from
      the G2-ext. The purified 28-kDa protein showed intense staining with silver on
      SDS-PAGE slab-gel under reducing conditions. This protein was digested with
      bacterial collagenase, and a 19-kDa fragment appeared on the gel. However, the
      protein was not susceptible to reduction with cyanogen bromide. The protein did
      not bind to hydroxyapatite crystals in the presence of 7.0 M urea, and also did
      not bind to some lectins. On SDS-PAGE under non-reducing conditions, the protein
      migrated as two bands; a new band appeared at approximately the 85-kDa region in
      addition to the original 28-kDa band. The amino acid compositions of the protein
      were similar to those of the alpha 1-pN-propeptide of type I procollagen obtained
      from other tissues.

PMID- 8158289
TI  - New York State baccalaureate performance on NCLEX: implications for faculty.
AB  - First-time candidates' performance on the NCLEX-RN Examination is of special
      concern to faculty teaching at the baccalaureate level, because the passing rate
      for these candidates is lower than for associate degree and diploma candidates.
      This paper focuses on how first-time baccalaureate degree candidates perform on
      the NCLEX-RN Examination, examines academic as well as nonacademic predictors of
      success, describes programs used to improve the pass rate at several
      baccalaureate programs, and presents a discussion of curriculum analysis.

PMID- 8158288
TI  - Concentrations of lomefloxacin in radicular cyst and oral tissues following
      single or multiple oral administration.
AB  - Concentrations of lomefloxacin in serum, the wall and fluid of radicular cyst,
      gingiva, and jawbone following single or multiple oral administration were
      measured. The highest concentrations of lomefloxacin in serum, cyst wall, cyst
      fluid, gingiva, and jawbone occurred at 3 h after multiple administration, and
      were 2.31 micrograms/ml, 4.06 micrograms/g, 1.54 micrograms/ml, 4.72 micrograms/g
      and 2.79 micrograms/g, respectively. The mean concentration ratios of wall/serum,
      fluid/serum, fluid/wall, gingiva/serum, and jawbone/serum at the highest
      concentrations were 1.74, 0.73, 0.47, 2.52 and 1.20, respectively. Although most
      lomefloxacin concentrations in cyst and oral tissues following single oral
      administration did not exceed the MICs for 80% of clinically isolated strains of
      alpha-hemolytic streptococci, Staphylococcus aureus and Niesseria spp., most of
      those obtained after multiple oral administration exceeded the MICs except in the
      case of fluid.

PMID- 8158290
TI  - Levels of political participation and political expectations among nurses in New
      York State.
AB  - The purpose of this study was to investigate the relationship of area of
      practice, educational level, and membership in a professional organization to
      political participation and political expectations among a group of 108
      registered nurses. "The Political Expectations and Participation Questionnaire"
      (PEPQ) (Daffin, 1988) was used to identify the nine political roles of voter,
      campaigner, player, monitor, networker, spokesperson, negotiator, leader, and
      lobbyist. It was found that nurses with master's or doctoral degrees had
      significantly higher levels of political participation than did nurses with
      baccalaureates, associate degrees, or diplomas. Nurse educators were found to
      have significantly higher levels of political participation than nurses in
      clinical practice. Members of professional organizations had significantly higher
      levels of political participation with respect to campaigner, player, and leader
      roles. No significant differences in levels of political expectation were found
      with respect to area of practice or membership in a professional organization.

PMID- 8158291
TI  - Adopt-A-School Program: recruitment initiative of New York Counties Registered
      Nurses Association. District 13 education committee.
AB  - The goal of this program was to alleviate the existing nursing shortage in New
      York City by developing recruitment models appropriate for students in the City's
      high schools. The rationale was that well-informed nurses could create an
      attractive image of nursing by presenting programs to students, teachers, and
      guidance counselors. The program was successful in clarifying misconceptions and
      increasing the knowledge base regarding health issues and concerns and the role
      of the nurse.

PMID- 8158292
TI  - Bibliography--nurse managed care.

PMID- 8158293
TI  - New York State, the leader in nurse registration: 1898-1908.
AB  - This historical paper traces the development and implementation of New York
      state's nurse registration law from 1898 until 1908. It recounts the
      disorganization, conflict, and division within the nursing community during its
      early years of professionalization and the work that Lavinia Dock, Sophia Palmer,
      and others did to organize the nursing profession. Dock and Palmer, working
      through the Society of Superintendents of Training Schools, as well as Ethel
      Gordon Fenwick, who founded the International Council of Nurses, stimulated the
      development of state nursing associations within the U.S. Immediately after its
      organization, the New York State Nurses Association undertook the legislative
      process that led to what was considered a model registration law. The paper
      traces the political process that New York's nursing leaders pursued to develop
      the legislation, and the educational and practice reforms that evolved from their
      efforts.

PMID- 8158294
TI  - Comparison of the echocardiographic effects induced by physiological ageing and
      hypertension on the left and right ventricle.

PMID- 8158295
TI  - Low mid-wall fractional shortening identifies a subgroup of hypertensive patients
      with increased left ventricular mass and ambulatory blood pressure.

PMID- 8158296
TI  - Effect of changes in blood pressure and left ventricular mass induced by
      antihypertensive treatment on ventricular arrhythmias in essential hypertension.

PMID- 8158297
TI  - Prevalence of electrocardiographic left ventricular hypertrophy in malignant
      hypertension and its correlation with renal function.

PMID- 8158298
TI  - Limited value of the electrocardiogram in detecting hypertensive left ventricular
      hypertrophy.

PMID- 8158300
TI  - Effect of anti-oxidants on acute blood pressure response to smoking in
      normotensives and hypertensives.

PMID- 8158299
TI  - Lipoproteins and angiotensin II exert synergistic effects on signalling processes
      in vascular smooth muscle cells.

PMID- 8158301
TI  - Protein kinase C and calcium distribution in vascular smooth muscle cells from
      spontaneously hypertensive rats.

PMID- 8158302
TI  - Effects of lipoproteins on the expression of the early growth response gene-1 and
      on DNA synthesis in rat vascular smooth muscle cells.

PMID- 8158303
TI  - Renin-dependent hypertension induces smooth muscle polyploidy in large and small
      vessels.

PMID- 8158305
TI  - Increased gene expression of angiotensin II type 1A receptor in aortic smooth
      muscle cells of cyclosporin A-induced hypertensive rats.

PMID- 8158304
TI  - Spontaneously hypertensive rats with diabetes: effects of some vasoconstrictors
      on isolated small arteries.

PMID- 8158306
TI  - Calcium channels in the vascular smooth muscle of spontaneously hypertensive
      rats.

PMID- 8158307
TI  - Proliferative effects of low-density lipoprotein subfractions on vascular smooth
      muscle cells: potentiation by insulin.

PMID- 8158308
TI  - Skin microvascular alterations in patients with chronic congestive heart failure.

PMID- 8158309
TI  - Evaluating sympathetic activity in human hypertension.
AB  - AIM: To review the use of plasma norepinephrine to evaluate sympathetic activity
      in humans, and to discuss the improvement in assessment of human sympathetic
      activity brought about by the norepinephrine spillover method and by
      microneurography. METHOD: Literature survey. RESULTS: These methods have
      limitations, and an accurate assessment of sympathetic cardiovascular control
      should not be limited to an investigation of sympathetic nerve firing or
      norepinephrine secretion but include cardiac and vascular responses. These
      responses can be assessed by traditional pharmacological means (for example, a
      reduction in vascular resistance induced by alpha-adrenergic blockade) or by a
      variety of approaches aimed at examining sympathetic cardiovascular modulation in
      a more integrated fashion, such as the recently developed power spectrum analysis
      of blood pressure and heart rate. CONCLUSION: The sensitivity and specificity of
      all these methods is still under investigation, but in almost every case an
      increase in sympathetic cardiovascular influence has been reported to occur in
      hypertension, indicating that sympathetic activation has a pathogenic effect on
      this condition.

PMID- 8158310
TI  - Divergent responses of common carotid artery intimal-medial thickness to high
      blood pressure and hypercholesterolaemia in relation to age.

PMID- 8158311
TI  - Lipoprotein-induced expression of the sis oncogene in human arterial endothelial
      cells.

PMID- 8158312
TI  - Impaired endothelium-dependent relaxation in two-kidney, one clip Goldblatt
      hypertension: effect of vasoconstrictor prostanoids.

PMID- 8158313
TI  - Nitric oxide and eicosanoid interactions in kidneys of Lyon hypertensive rats.

PMID- 8158314
TI  - Effect of nitric oxide and prostaglandins on renal function in insulin-resistant
      hypertensive dogs.

PMID- 8158315
TI  - The humoral, renal and pressor effects of systemic L-arginine infusion in
      hypertensive patients.

PMID- 8158316
TI  - Increased plasma endothelin-1 immunoreactive levels in vasculitis: a clue to the
      use of endothelin-1 as a marker of vascular damage?

PMID- 8158317
TI  - Forearm vasodilation in response to acetylcholine is increased by potassium in
      essential hypertensive patients.

PMID- 8158318
TI  - Plasma endothelin is increased in young essential hypertensives but not in
      elderly essential or diabetic hypertensives.

PMID- 8158319
TI  - The sympathetic response to different orthostatic challenges and its daytime
      variation, assessed by power spectral analysis of heart rate.

PMID- 8158320
TI  - Blood pressure and heart rate variability in clinical models of cardiac
      denervation, sympathicolysis and sympathico- and parasympathicolysis.

PMID- 8158321
TI  - Sympathetic nerve traffic and baroreflex control of circulation in obese
      patients: a preliminary report.

PMID- 8158322
TI  - Improved baroreflex control of the heart rate with chronic beta-adrenergic
      blockade in mild hypertension.

PMID- 8158323
TI  - Enalaprilat suppresses hindlimb noradrenaline spillover during exercise in the
      rabbit.

PMID- 8158324
TI  - Coincidence of calcitonin gene-related peptide immunoreactivity and terminal
      fields of efferents from the cardiovascular portion of the fastigial nucleus:
      preliminary report.

PMID- 8158325
TI  - Short- and long-term reproducibility of techniques employed to assess sympathetic
      tone in humans: a preliminary report.

PMID- 8158326
TI  - Partial preservation of nocturnal fall in blood pressure in patients with
      catecholamine-producing tumours.

PMID- 8158327
TI  - Reduced response with ageing to sympatho-excitatory and sympatho-inhibitory
      stimuli in humans.

PMID- 8158328
TI  - The role of calcium ions in the regulation of rhythmic oscillations in blood
      pressure.

PMID- 8158329
TI  - Evidence for altered baroreceptive control of heart rate in pure autonomic
      failure.

PMID- 8158330
TI  - Variability in arterial blood pressure at rest depends on the sensitivity of the
      baroreflex.

PMID- 8158332
TI  - Effects of static handgrip exercise and post-handgrip forearm muscle ischaemia on
      the heart rate and arterial blood pressure rhythmicity in normal humans.

PMID- 8158331
TI  - Effects of water immersion on forearm vascular resistance in normotensive
      subjects.

PMID- 8158333
TI  - Activation of renal R1 chemoreceptors increases vasopressin concentration in
      rabbits.

PMID- 8158334
TI  - Changes in beta-adrenergic receptivity during human left ventricular hypertrophy
      due to pressure overload.

PMID- 8158335
TI  - Increased intracellular calcium response in glomerular mesangial cells from
      spontaneously hypertensive rats.

PMID- 8158336
TI  - Protein excretion and renal adaptation of transgenic mRen2 rats to changing oral
      sodium loads.

PMID- 8158338
TI  - Is insulin-like growth factor 1 a determinant of renal haemodynamics in obesity
      hypertension?

PMID- 8158337
TI  - Association between smoking and micro-albuminuria in hypertensive patients with
      type 2 diabetes mellitus.

PMID- 8158339
TI  - Effect of intravenous sodium chloride on renal sodium and calcium handling in
      hypertensive patients with different sensitivities to sodium chloride.

PMID- 8158340
TI  - Association between extracellular volume expansion and urinary calcium excretion
      in normal humans.

PMID- 8158341
TI  - Urinary albumin excretion as an index of total cardiovascular stress:
      relationship to macro-angiopathic complications in non-insulin-dependent diabetes
      mellitus.

PMID- 8158342
TI  - Hypertension and stroke: opportunities for prevention and prospects for
      protection.
AB  - Risks associated with hypertension: Hypertension is a major factor in
      haemorrhagic and atherothrombotic stroke. Reduction of blood pressure reduces
      stroke risk by up to 40% in all hypertensive populations. Many older patients who
      would benefit from antihypertensive therapy are currently not adequately treated.
      Need for further trials: Further controlled clinical trials are required to
      confirm the optimum regimen for secondary prevention after a stroke or transient
      ischaemic attack. Knowledge of the mechanisms of ischaemic damage to the brain is
      increasing, and several pharmacological approaches to neuroprotection have been
      shown to be of benefit in experimental models. Evaluation of humans requires an
      accurate diagnosis of stroke type and improved outcome measures. CONCLUSIONS: The
      optimal benefit of protection from acute strokes will depend on a better
      understanding of the ideal haemodynamic profile and the early and appropriate
      delivery of a neuroprotective drug to the site of ischaemia.

PMID- 8158343
TI  - Search for the genes of human essential hypertension.
AB  - BACKGROUND: Hypertension shares several characteristics with diabetes,
      atherosclerosis and asthma. These common diseases are caused by environmental
      factors and predisposing genes and they represent a major cost in developed
      countries. Use of molecular techniques: Much information is expected from the
      identification of the molecular bases of these diseases, and from the molecular
      characterization of the predisposing variants and their effects on the clinical
      manifestations of these pathologies. Hypertension is now a target for genetic
      studies, and some interesting results have been obtained in humans and in animal
      models.

PMID- 8158344
TI  - Does captopril improve the diagnostic value of 99mTc
      diethylenetriaminepentaacetic acid renography for renal artery stenosis?

PMID- 8158345
TI  - Effect of sodium bicarbonate and sodium chloride on arterial blood pressure,
      plasma renin activity and urinary prostaglandins in healthy volunteers.

PMID- 8158346
TI  - Magnetic resonance angiography in the diagnosis of renal artery stenosis.

PMID- 8158347
TI  - Autoimmune mechanisms may be involved in renovascular hypertension due to
      fibrodysplasia but not to atherosclerosis.

PMID- 8158348
TI  - Effect of cicaprost on the progression of diabetic nephropathy in
      uninephrectomized streptozotocin-induced diabetic rats.

PMID- 8158349
TI  - Renal kallikrein is a determinant of salt sensitivity.

PMID- 8158350
TI  - Urinary kallikrein excretion and plasma atrial natriuretic peptide in human salt
      sensitive hypertension.

PMID- 8158351
TI  - Comparative analysis of atrial natriuretic peptide receptor expression in rat
      tissues.

PMID- 8158352
TI  - Is human atrial natriuretic peptide unstable at -80 degrees C?

PMID- 8158353
TI  - Atrial natriuretic peptide and blunted renal responses to volume expansion in
      rats with Heymann nephritis.

PMID- 8158354
TI  - The pharmacology of CGS 25462: a potent, orally bioavailable, long-acting
      inhibitor of neutral endopeptidase 24.11.

PMID- 8158355
TI  - Inhibition of endopeptidase EC 3.4.24.11 by candoxatril lowered blood pressure
      and increased urinary but not plasma atrial natriuretic peptide in essential
      hypertension.

PMID- 8158356
TI  - Cardiac renin is kidney-derived.

PMID- 8158357
TI  - Modulation of blood pressure and the renin-angiotensin system in transgenic and
      spontaneously hypertensive rats afer ovariectomy.

PMID- 8158358
TI  - Results of the Italian Multicenter Study for Standardization of Renin Measurement
      with immunoradiometric assay: comparison with the conventional enzymatic method.

PMID- 8158359
TI  - Identification of AT1 receptors on human platelets and decreased angiotensin II
      binding in hypertension.

PMID- 8158360
TI  - Angiotensin converting enzyme expression in the inflammation zone of human
      myocardial infarction and rat model of skin injury.

PMID- 8158361
TI  - The possible role of angiotensin II subtype AT2 receptors in endothelial cells
      and isolated ischemic rat hearts.

PMID- 8158362
TI  - Renin-angiotensin system gene expression during compensatory renal hypertrophy in
      the rat.

PMID- 8158364
TI  - A novel assay of plasma prorenin using a renin inhibitor.

PMID- 8158363
TI  - Changes in plasma renin and angiotensin run in parallel after nephrectomy.

PMID- 8158365
TI  - Renin-angiotensin-aldosterone, sympathetic and endothelin systems in normal and
      hypertensive pregnancy: response to postural and volume load stimuli.

PMID- 8158366
TI  - Effect of losartan on short-term variability of blood pressure of renovascular
      hypertensive rats: a spectral study.

PMID- 8158367
TI  - Effect of sodium during pregnancy in the spontaneously hypertensive rat.

PMID- 8158368
TI  - Effects of pharmacological modulation of the renin-angiotensin-aldosterone system
      on salt sensitivity in patients with borderline hypertension.

PMID- 8158369
TI  - Clinical profile of essential hypertensives based on ion transport abnormalities.

PMID- 8158370
TI  - Abnormalities of sodium-magnesium exchange in erythrocytes from essential
      hypertensive patients.

PMID- 8158371
TI  - Increased sodium, potassium cotransport activity in salt-sensitive essential
      hypertensive patients.

PMID- 8158372
TI  - Essential hypertension, impaired glucose tolerance and hyperlipidaemia: multiple
      relationships with sodium-lithium countertransport.

PMID- 8158373
TI  - Erythrocyte sodium-lithium countertransport in insulin-dependent diabetics:
      correlation with membrane lipids, prorenin and micro-albuminuria.

PMID- 8158374
TI  - Wall shear stress and erythrocyte membrane microviscosity in hypertensive
      patients.

PMID- 8158375
TI  - Human cheek epithelial cell sodium transport activity in essential hypertension.

PMID- 8158376
TI  - Tissue-specific differences of cytosolic free sodium in spontaneously
      hypertensive rats.

PMID- 8158377
TI  - A potent inhibitor of the Na+,K+,Cl- cotransport system in urine from salt-loaded
      rats.

PMID- 8158378
TI  - The effects of hypertension and diabetes mellitus on the vascular reactivity of
      perfused mesenteric resistance arteries.

PMID- 8158379
TI  - Insulin resistance, hyperinsulinemia and hypertension.
AB  - Association between insulin resistance and hypertension: Insulin resistance and
      reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance
      or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese,
      non-diabetic patients with essential hypertension and their currently
      normotensive, lean young offspring and in some other conditions known to promote
      hypertension. Insulin resistance impairs glucose tolerance, while insulin
      resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and
      probably atherogenesis. Therefore, the common coexistence of a genetic
      predisposition for hypertension with insulin resistance helps to explain the
      frequent, although temporally often dissociated, occurrence of hypertension as
      well as dyslipidemia, obesity and type 2 diabetes in a given subject.
      Pathogenetic mechanisms: In the pathogenesis of hypertension, inappropriate
      vasoconstriction (due to dysbalance of vasoactive substances and/or raised
      cytosolic Ca2+) and/or a structural vasculopathy is a very important ultimate
      causative event. In the presumed mosaic of participating pressor mechanisms,
      distinct Na+ retention is almost obligatory with diabetes mellitus, while
      essential and particularly obesity-associated hypertension probably involves a
      tendency for sympathetic activation. Development of insulin resistance: Insulin
      resistance may develop as a consequence of an intracellular excess of Ca2+ or
      decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood
      flow, increased sympathetic activity or being overweight. Acute hyperinsulinemia
      on the one hand causes arterial vasodilation and on the other hand enhances renal
      sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may
      promote cardiovascular muscle cell proliferation and atherogenesis, and it has
      been proposed that insulin resistance in certain transmembranous cation exchange
      systems may elevate cytosolic Ca2+. Nevertheless, whether insulin resistance
      and/or hyperinsulinemia itself contribute to the pathogenesis of hypertension is
      still unclear.

PMID- 8158380
TI  - Increased activity in the nitric oxide pathway during chronic euglycemic
      hyperinsulinemia in the rat.

PMID- 8158381
TI  - Insulin does not modulate reflex forearm sympathetic vasoconstriction in patients
      with essential hypertension.

PMID- 8158382
TI  - Cellular cation exchange in arterial hypertension: effects of insulin resistance.

PMID- 8158383
TI  - Short-term effects of metformin on insulin sensitivity and sodium homeostasis in
      essential hypertensives.

PMID- 8158384
TI  - Very-low-density lipoprotein composition and endogenous insulin response in
      primary hypertension.

PMID- 8158385
TI  - Bioelectric impedance analysis of body composition in alcohol-related essential
      hypertension.

PMID- 8158386
TI  - Accuracy of the SpaceLabs 90207 ambulatory blood pressure measuring system in
      normotensive pregnant women determined by the British Hypertension Society
      protocol.

PMID- 8158387
TI  - Assessment of physical and mental activity using a standardized computer-assisted
      diary during ambulatory blood pressure monitoring.

PMID- 8158388
TI  - Cumulative sums analysis of twenty-four-hour blood pressure profiles in patients
      with sympathetic denervation.

PMID- 8158389
TI  - Reproducibility of ambulatory blood pressure monitoring in children.

PMID- 8158390
TI  - Nycthemeral blood pressure variability in obstructive sleep apnea syndrome:
      relationship to left ventricular hypertrophy and metabolic disorders.

PMID- 8158391
TI  - Diurnal blood pressure rhythm and urinary catecholamine excretion in obstructive
      sleep apnoea and essential hypertension.

PMID- 8158392
TI  - Hormonal profile of dipper and non-dipper patients with essential hypertension.

PMID- 8158393
TI  - Twenty-four-hour blood pressure in three age groups of hypertensive subjects
      during daily activity.

PMID- 8158394
TI  - Differences in body mass index and smoking habit between untreated essential
      hypertensive patients with or without altered blood pressure circadian rhythm.

PMID- 8158395
TI  - Regression of cardiac hypertrophy and night-time blood pressure reduction.

PMID- 8158396
TI  - Detection of renin messenger RNA by polymerase chain reaction in aldosterone
      producing adenomas.

PMID- 8158397
TI  - Relationship between vitamin D and the regional blood flow and vascular
      resistance in moderate arterial hypertension.

PMID- 8158398
TI  - The frequency of orthostatic hypotension in elderly patients with essential
      hypertension, isolated systolic hypertension and borderline hypertension.

PMID- 8158399
TI  - Plasma insulin is correlated with blood pressure only in subjects with a family
      history of hypertension or diabetes mellitus: results from 11,001 participants in
      the Heureka Study.

PMID- 8158400
TI  - How common is primary aldosteronism? Is it the most frequent cause of curable
      hypertension?

PMID- 8158401
TI  - Effect of atrial natriuretic factor on basal and stimulated pituitary-adrenal
      function in Cushing's and Addison's disease.

PMID- 8158402
TI  - Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS): a protocol for non
      invasive evaluation of carotid atherosclerosis in hypercholesterolaemic
      hypertensive subjects.

PMID- 8158403
TI  - Vascular wall thickness in hypertension: the Perindopril Regression of Vascular
      Thickening European Community Trial (PROTECT).

PMID- 8158404
TI  - The effects of omega-3 fatty acids on blood pressure and serum lipids in men at
      increased risk of cardiovascular disease.

PMID- 8158405
TI  - Blood pressure is reduced by short-time calorie restriction in overweight
      hypertensive women with a constant intake of sodium and potassium.

PMID- 8158406
TI  - Renin-angiotensin system in the pressor effect of acute N-omega-nitro-L-arginine
      methyl ester.

PMID- 8158407
TI  - Randomly allocated crossover study of various levels of sodium intake in patients
      with mild hypertension.

PMID- 8158408
TI  - Effect of canrenone and hydrochlorothiazide on the development of hypertension in
      rat models of genetic hypertension.

PMID- 8158409
TI  - Long-acting calcium antagonists: amlodipine versus nifedipine gastrointestinal
      therapeutic system (GITS).

PMID- 8158410
TI  - Antihypertensive effects of nifedipine gastrointestinal therapeutic system on
      clinic and ambulatory blood pressure in essential hypertensives. Italian GITS
      Study Group.

PMID- 8158411
TI  - Antihypertensive and humoral effects of verapamil and lacidipine in combination
      in hypertensive patients.

PMID- 8158412
TI  - Interaction of indomethacin with felodipine and enalapril.

PMID- 8158413
TI  - Oral pharmacokinetics and pharmacodynamics of idrapril calcium, the prototype of
      a new class of angiotensin converting enzyme inhibitors, in humans.

PMID- 8158414
TI  - Combination therapy versus monotherapy in hypertensive patients: an Italian
      multicentre study.

PMID- 8158415
TI  - Cardiac and nephroprotective effects of angiotensin converting enzyme inhibitor
      treatment in the renal ablation model.

PMID- 8158416
TI  - Effects of pravastatin in dyslipidaemic patients with and without hypertension.

PMID- 8158417
TI  - Obese hypertensive patients are less effectively treated than lean hypertensives.

PMID- 8158418
TI  - Tissue plasminogen activator in saliva of hypertensives treated with angiotensin
      converting enzyme inhibitors or calcium antagonists.

PMID- 8158419
TI  - Is the renal dopaminergic system involved in the natriuretic effect of
      felodipine?

PMID- 8158420
TI  - Effects of blood pressure reduction with trandolapril and enalapril on left
      ventricular hypertrophy and exercise tolerance.

PMID- 8158421
TI  - Role of bradykinin in the angiotensin converting enzyme inhibitor-induced
      impairment of systemic adaptation to dietary sodium removal in rats.

PMID- 8158422
TI  - Early treatment with nitrendipine may prevent endothelial dysfunction in
      mesenteric small arteries of spontaneously hypertensive rats.

PMID- 8158423
TI  - Effect of perindopril and amiloride/hydrochlorothiazide on haemodynamics and
      vessel wall properties of large arteries.

PMID- 8158424
TI  - Determinants of left ventricular mass reduction in essential hypertension.

PMID- 8158425
TI  - Comparative study of diltiazem and lisinopril in hypertension: similar
      improvements in diastolic function despite different effects on left ventricular
      mass and ambulatory blood pressure.

PMID- 8158426
TI  - The effects of diuretic and beta-blocker treatment on cardiac and vascular
      structural changes in untreated essential hypertensive patients.

PMID- 8158427
TI  - Effects of quinapril and verapamil versus atenolol on blood pressure during
      dynamic leg exercise.

PMID- 8158428
TI  - Effects of fosinopril and hydrochlorothiazide on cerebral perfusion in
      uncomplicated essential hypertension.

PMID- 8158429
TI  - Round table 1. Do transgenic techniques help us to understand hypertension?

PMID- 8158430
TI  - Round table 2. First-line drugs: the position of the World Health Organization
      International Society of Hypertension.

PMID- 8158431
TI  - Round table 2. A critique of the Fifth Joint National Committee Report on
      Detection, Evaluation and Treatment of High Blood Pressure.

PMID- 8158432
TI  - Critical assessment of international clinical development programmes for new
      antihypertensive drugs.
AB  - Criteria for assessing new antihypertensive drugs: The major factors to be
      assessed when registering a new antihypertensive drug are chemical quality, drug
      efficacy, safety and tolerability in the short and long term. Critical criteria
      for acceptance of the drug may include the degree of originality, the validity of
      the dose range and administration schedule and the degree of usefulness compared
      with other drugs used in the same patient group. Future clincial development: The
      clinical development of new antihypertensive drugs is becoming increasingly
      complex. Similar errors are repeated from one clinical development programme to
      another. Simple but original protocols, using average rather than closely
      selected patient sets, and clearcut dose-ranging studies will reflect a better
      use of human and financial resources.

PMID- 8158433
TI  - Physical fitness and blood pressure.
AB  - AIM: Epidemiological studies suggest an inverse relationship between physical
      activity or fitness and blood pressure. We therefore performed a meta-analysis of
      36 controlled intervention studies. RESULTS: The weighted net blood pressure
      response to dynamic aerobic training averaged -5.3 mmHg for systolic and -4.8
      mmHg for diastolic pressure. The interstudy variation in the change in blood
      pressure was mainly dependent on the initial blood pressure status and the
      efficacy of the training programme. The weighted net change in blood pressure
      with endurance training averaged -3/-3 mmHg in normotensives, -6/-7 mmHg in
      borderline hypertensives and -10/-8 mmHg in hypertensives. Reductions in blood
      pressure have also been observed for measurements during exercise and during
      daytime ambulatory monitoring; sleep blood pressure was not, however,
      significantly altered.

PMID- 8158435
TI  - Meta-analysis as a guide to clinical practice.
AB  - BACKGROUND: Meta-analysis is now widely used in order to increase the power of
      individual clinical studies. Important far-reaching conclusions have been derived
      by pooling the results of studies which in isolation would not be large enough to
      reach definitive conclusions. While the statistical power is thereby amplified,
      so is the potential for error. OBJECTIVE: To assess the potential and the
      pitfalls of meta-analysis as a guide to clinical practice. CONCLUSIONS:
      Conclusions derived from meta-analysis may be influenced by unrecognized
      selection bias and heterogeneity of studies included. Publication of the results
      may be in a form which does not lend itself readily to critical analysis and
      misleading results may therefore be accepted.

PMID- 8158434
TI  - Renal vasodepressor mechanisms: the medullipin system.
AB  - Renal vasodepressor hormone: Medullipin I is the renomedullary vasodepressor
      hormone secreted by the renomedullary interstitial cells of the renal papilla. It
      is conveyed to the liver where it is converted to its active form, medullipin II.
      Medullipin II is a vasodilator that suppresses sympathetic tone and causes
      diuresis and natriuresis. Its actions are opposite to those of angiotensin II.
      These are feedback control systems. The secretion and conversion of medullipin is
      related to the cytochrome P-450 dependent enzyme system of kidney and liver.
      Deficiency of medullipin: A deficiency of medullipin is considered to contribute
      to the pathogenesis of various hypertensive states. There are three known causes
      for such a deficiency, (1) removal of renomedullary interstitial cells by
      bilateral nephrectomy, renal surgical papillectomy, chemical papillectomy,
      papillary atrophy or necrosis; (2) decrease in number and damage to renomedullary
      interstitial cells in accelerated experimental hypertension and malignant
      hypertension of humans; and (3) dysfunction of renomedullary interstitial cells
      as mediated by angiotensin II, by resetting of the effect of increased renal
      artery perfusion pressure, by stimulation of the renal sympathetic nerve, by
      inhibition of nitric oxide synthesis and possibly by inhibition of cyclo
      oxygenase. Secretion of Medullipin I: The main factor influencing secretion of
      medullipin I by the kidney appears to be the renal artery perfusion pressure.
      Elevation of this pressure is attenuated by the presence of medullipin I in the
      renal venous effluent. Lowering the pressure below normal shuts off this
      secretion. This is opposite to the effects of perfusion pressure on renin
      secretion, as elevation shuts off renin secretion while depression turns it
      on.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158436
TI  - Gene regulation of beta-1-adrenergic receptor in genetically hypertensive rats.

PMID- 8158437
TI  - Renal renin activity in recombinant inbred strains is related to abnormal renin
      gene: the role of blood pressure changes.

PMID- 8158438
TI  - Expression of the insulin receptor gene in liver and kidney of rats with genetic
      hypertension.

PMID- 8158439
TI  - Resistance vessel structure and the pathogenesis of hypertension.
AB  - AIM: To review evidence on the influence of resistance vessel structure in the
      pathogenesis of essential and experimental hypertension. Results of review: In
      essential hypertension, recent experiments have provided direct evidence that the
      structure of the more proximal resistance vessels (small arteries) is abnormal,
      with a reduction in the lumen and an increase in the ratio of medial thickness to
      lumen diameter (media: lumen ratio). Furthermore, the abnormal structure appears
      to be due more to 'remodelling' (a rearrangement of a normal amount of material
      around a smaller lumen), rather than to a growth process, in agreement with the
      original Folkow hypothesis. These abnormalities are usually closely correlated
      with blood pressure, but whether the abnormalities cause, or are the effect of,
      the increased blood pressure remains unclear. However, in animal experiments
      where procedures have been used to create a discrepancy between blood pressure
      and small artery structure (e.g., unclipping a rat made hypertensive by the
      Goldblatt technique), the blood pressure has not been correlated with small
      artery structure. This suggests that the abnormal structure of small arteries in
      hypertension is adaptive, rather than causal. Therefore if the resistance vessel
      structure as a whole is a primary factor in essential hypertension, it seems that
      it must be the more distal resistance vessels which are responsible. There is
      evidence that alterations in the structure and function of renal afferent
      arterioles could have a pathogenetic effect in genetic hypertension, and it is
      suggested that further work be directed towards testing this possibility.

PMID- 8158440
TI  - The Bergen Blood Pressure Study: twenty-four-hour ambulatory blood pressure is
      increased in offspring of hypertensive parents.

PMID- 8158441
TI  - Blood pressure, age, sex and mortality in the elderly: an epidemiological survey
      with 6 years of follow-up.

PMID- 8158442
TI  - Lipid-lipoprotein profile in pregnant women with primary hypertension and in
      normotensive pregnant women with a positive family history of hypertension.

PMID- 8158443
TI  - Parental left ventricular hypertrophy predicts Doppler-derived diastolic filling
      in young offspring of hypertensive subjects.

PMID- 8158444
TI  - Early cardiac and vascular structural changes in subjects with parental
      hypertension.

PMID- 8158445
TI  - M235T variant of the human angiotensinogen gene in unselected hypertensive
      patients.

PMID- 8158446
TI  - Arterial compliance in familial hypercholesterolaemia: a preliminary report.

PMID- 8158447
TI  - Selective increase in popliteal artery wall stiffness in long-term smokers.

PMID- 8158448
TI  - Arterial compliance in obese young subjects: a preliminary report.

PMID- 8158449
TI  - Vessel wall properties of large arteries and endurance training.

PMID- 8158450
TI  - Circadian hemodynamics in heart transplant recipients.

PMID- 8158451
TI  - Cardiac adaptation to obesity in elderly hypertensive patients.

PMID- 8158452
TI  - A centripetal shift in intravascular volume triggers the onset of early cardiac
      adaptation in hypertension.

PMID- 8158453
TI  - Improved prediction of left ventricular mass from ambulatory blood pressure
      monitoring using average tension-time index.

PMID- 8158454
TI  - The pathology of the human notochord.

PMID- 8158455
TI  - pS2 protein in gastric carcinoma and normal gastric mucosa: association with
      clincopathological parameters and patient survival.
AB  - The presence of pS2 protein (pS2) was studied in a total of 120 consecutive
      patients with gastric carcinomas. This immunohistochemical study found pS2
      expression in 48 per cent (n = 58) of carcinomas. pS2 expression was also
      detected in normal gastric mucosa in 95 per cent (n = 102) of specimens in upper
      antral mucopeptic glands and deep foveolar cells of the gastric pits but not in
      intestinal metaplasia. There was a significant statistical correlation between
      pS2 expression and extent of tumour growth (pT state) and expression of
      pepsinogen II by the tumours. There was no statistical correlation with clinical
      features such as patient age or sex or other pathological parameters (tumour
      stage, size, grade, and localization or growth pattern according to histological
      classification). There were no statistically significant differences in survival
      times between patients with pS2-positive and pS2-negative tumours. In contrast to
      findings concerning breast cancer, pS2 expression in gastric carcinomas had no
      influence on the patient's prognosis. On the other hand, strong expression of pS2
      by surface epithelium of normal gastric mucosa may indicate that pS2 might play a
      role in physiological cell renewal of normal gastric mucosa.

PMID- 8158456
TI  - Role of respiratory viral infection in SIDS: detection of viral nucleic acid by
      in situ hybridization.
AB  - There is considerable evidence suggesting that respiratory viral infection is
      involved in the genesis of the sudden infant death syndrome (SIDS), with rates of
      about 20 per cent of SIDS victims compared to about 13 per cent of controls.
      Since the techniques used previously are prone to under-reporting from autopsy
      material, non-isotopic in situ hybridization (NISH) has been used to detect viral
      nucleic acid in lung in SIDS. Forty-five SIDS cases (30 males) were examined (age
      range 3 weeks-14 months, mean age 3.9 months). Thirty non-SIDS cases (15 males)
      were also examined (age range 5 weeks-24 months, mean age 9.0 months). Eleven of
      45 (24.4 per cent) SIDS cases were positive by NISH compared to 1 of 30 (3.3 per
      cent) non-SIDS cases (P = 0.012). There were eight cases of adenovirus type 5,
      two cases of respiratory syncytial virus (RSV), and one case of parainfluenza
      virus type 2. The one positive control case was adenovirus type 5. Only lung
      parenchyma was examined here. Additional examination of the upper respiratory
      tract may increase the number of positive cases.

PMID- 8158457
TI  - Image analysis of Ag-NOR proteins in transitional cell bladder cancer.
AB  - Nuclear organizer regions (Ag-NORs) were visualized using the standard silver
      staining technique in biopsy specimens from 112 bladder carcinomas. The area of
      individual Ag-NOR dots and the area of Ag-NOR protein/nucleus were measured using
      a Quantimet 570 image analyser and the results were then correlated with
      clinical, histological, and quantitative prognostic factors, and survival. The
      mean area of Ag-NOR dots was not significantly related to any of the features
      analysed. The mean area of Ag-NOR protein/nucleus was related to WHO grade (P =
      0.0004), papillary status (P = 0.004), DNA ploidy (P = 0.02), S-phase fraction (P
      = 0.02), mitotic frequency/mm2 of enoplastic epithelium (P = 0.005), mean nuclear
      area (P = 0.001), and SD of nuclear area (P = 0.001). In the entire cohort, the
      mean area of Ag-NOR protein/nucleus was related to progression with a borderline
      significance (P = 0.09), while in survival analysis only Ag-NOR count/nucleus had
      prognostic value (P = 0.010). In Ta-T1 tumours, Ag-NOR protein area/nucleus
      predicted progression (T-category) (P = 0.016) and survival (P = 0.014)
      significantly. Also, the mean area of individual Ag-NOR dots (P = 0.026) and Ag
      NOR count/nucleus (P = 0.014) were related to prognosis in Ta-T1 tumours.

PMID- 8158458
TI  - Expression of p53 in oligodendrogliomas.
AB  - The expression of the nuclear protein p53 in oligodendrogliomas was investigated
      by immunohistochemistry, using a monoclonal anti-p53 antibody (DO-7) on formalin
      fixed, paraffin-embedded material in 84 histologically verified cases, and
      compared with the histopathological grade and survival. p53-immunoreactive cells
      were found in 75 per cent of the samples acquired at the first biopsy. The p53
      labelling index was not related to the degree of nuclear anaplasia. Tumour cases
      with more than 75 per cent p53 immunostained cells had a rapidly fatal clinical
      course. However, no significant correlation was found between p53 labelling index
      and tumour grade, mitotic index, or ploidy status. In most tumour recurrences (n
      = 25), the p53 labelling index increased or remained at the level of the first
      biopsy. In five cases (6 per cent), p53 was absent in the first sample as well as
      in the recurrence. Irrespective of the underlying aberration of either the gene
      or the metabolic pathway of p53, it is concluded that a high percentage (i.e.,
      more than 75 per cent) of p53-immunolabelled cells is predictive of an
      unfavourable clinical course, while a percentage lower than 75 per cent
      immunoreactive cells does not exclude a rapid fatal outcome.

PMID- 8158459
TI  - Expression of hepatocyte growth factor mRNA during oval cell activation in the
      rat liver.
AB  - The customary wave of hepatocyte regeneration which occurs in the rat liver after
      two-thirds partial hepatectomy can be abolished by oral administration of the
      carcinogen 2-acetylaminofluorene. Instead, regeneration is achieved through the
      proliferation and differentiation of potential stem cells (oval cells) which
      appear to emanate from the portal space. Ultrastructural studies have illustrated
      the undifferentiated nature of these cells in the first 3 days after resection,
      but very rapidly they acquire features of small hepatocytes or biliary epithelia.
      Oval cell progeny can form either cohesive columns of cells within sinusoids
      which may later differentiate into new hepatic plates, or single cells that can
      insinuate within existing plates. Using a 35S antisense riboprobe to hepatocyte
      growth factor (HGF) mRNA, the synthesis of HGF mRNA was observed in sinusoid
      lining cells. There were few HGF mRNA-expressing cells in the liver removed at
      resection, but numbers steadily increased in the remnant over the next 7 days. In
      particular, an almost nine-fold increase in the density of HGF mRNA-producing
      cells occurred in the periportal areas, resulting in approximately double the
      density present within the centrilobular parenchyma. The superabundance of HGF
      producing cells in the immediate vicinity of oval cell proliferation and
      differentiation strongly suggests that this growth factor is involved in all
      aspects of stem cell behaviour--proliferation, migration, and differentiation,
      through a paracrine mechanism.

PMID- 8158460
TI  - Cytotoxicity of oxidized low-density lipoprotein to mouse peritoneal macrophages:
      an ultrastructural study.
AB  - Mouse peritoneal macrophages (MPM) were incubated in culture medium containing
      low-density lipoprotein (LDL), oxidized LDL (oxLDL), or as controls, for 24 h.
      Scanning electron microscopy of MPM exposed to oxLDL showed loss of membrane
      ruffles and extensive plasmalemmal 'blebbing'. Transmission electron microscopy
      showed changes in up to 50 per cent of the cells, including vacuolation of the
      rough endoplasmic reticulum and reorganization of heterochromatin in the nuclei,
      characteristic of apoptosis. These changes were not seen in controls, nor in
      macrophages exposed to native LDL. Electron-dense crystals were found in the
      cytoplasm of 1 in 50 of cells exposed to oxLDL. These were found to have a high
      content of calcium and phosphorus. It is proposed that oxLDL is capable of
      inducing apoptosis, which might explain the origin of the necrotic base of
      advanced atherosclerotic plaques.

PMID- 8158461
TI  - Presidential address. Dr. Stoll's wormy world revisited: the neglected animal
      diseases.

PMID- 8158462
TI  - Introduction of Dr. Martin L. Adamson as the Henry Baldwin Ward Medalist for
      1993.

PMID- 8158463
TI  - Acceptance of the Henry Baldwin Ward Medal.

PMID- 8158464
TI  - Altered behavior in two species of blattid cockroaches infected with Moniliformis
      moniliformis (Acanthocephala).
AB  - Moniliformis moniliformis-infected Periplaneta australasiae and Blatta orientalis
      were less active than uninfected controls in behavioral arena tests under both
      red and white light regimes. There was a strong interaction between light regime
      and parasitism for substrate use by P. australasiae. Under red light, parasitism
      decreased the use of black horizontal surfaces, whereas under white light,
      parasitism increased the use of black horizontal surfaces. In contrast, B.
      orientalis substrate use was unaffected by parasitism, although infected animals
      were less active than uninfected conspecifics under both light regimes. For both
      species, parasitism did not change the percentage of time spent in light, the
      freeze time, or the directional response to light.

PMID- 8158465
TI  - In vitro culture of equine strongylidae to the fourth larval stage in a cell-free
      medium.
AB  - An efficient and reliable method is described for the culture of equine
      strongyles from the third (L3) to the fourth (L4) larval stage. Medium consists
      of 50% fetal calf serum and 50% NCTC with additions of L-glutamine, NaHCO3, yeast
      extract, bactopeptone, and dextrose. The gas phase used is of prime importance;
      it is a mixture of 10% CO2, 5% O2, and 85% N2. Strongylus vulgaris, Strongylus
      edentatus, Strongylus equinus, Triodontophorus brevicauda, Triodontophorus
      serratus, Triodontophorus tenuicollis, Oesophagodontus robustus, Cylicocyclus
      insigne, and mixed species of cyathostomes were cultured to the L4 stage.
      Oesophagodontus robustus was cultured to the fifth larval stage. Depending on
      species, 44-95% of Strongylinae L3 inoculated into this system molted to L4.
      Although some development of the Cyathostominae L3 occurred, only a small portion
      (1%) completed ecdysis to L4. Viability in cultures of all species remained high
      (> 60-70% larvae surviving) for at least 4 wk (cyathostomes) and as long as 6 mo
      (S. edentatus). The addition of equine hemin to cultures of S. vulgaris and O.
      robustus L4 enhanced development and prolonged viability of these larvae. Hemin
      had no effect on cultures of S. edentatus or S. equinus, and it was not tested in
      cultures of other species.

PMID- 8158466
TI  - Babesia equi erythrocytic stage continuously cultured in an enriched medium.
AB  - Babesia equi was continuously cultured through 90 passages in an enriched
      chemically defined basal medium (HL-1) supplemented with 20% fetal bovine serum
      and serum replacement factors, including lipid-rich bovine serum albumin, bovine
      insulin, and human transferrin. Cryopreservation and subsequent recovery of B.
      equi were easily achieved. Inoculation of a splenectomized and an intact horse
      with cultured infected erythrocytes resulted in parasitemias and B. equi in vitro
      reisolation from both animals. In vitro forms of the parasite resembled in vivo
      forms. After establishment, parasitemias of 10-15% were commonly observed.

PMID- 8158467
TI  - Early migration and development of Dirofilaria immitis in the ferret, Mustela
      putorius furo.
AB  - Twenty-four female ferrets, approximately 4 mo of age, were subcutaneously
      inoculated with 60 infective larvae of Dirofilaria immitis to determine migration
      and development of the worms until they became young adults in the heart and
      associated vessels. Twelve groups of 2 ferrets each were examined at 3, 5, 11,
      15, 21, 49, 56, 63, 70, 91, 119, and 140 days postinoculation, respectively, to
      recover worms. Total worm recovery from each ferret varied from 1.6 to 79.3%.
      Worms were found mostly in subcutaneous tissue and muscle from the beginning of
      infection up to and including day 91. Worms were first recovered from the heart
      at day 70, when 3.8% of the worms had reached this site. By day 119, essentially
      all of the worms had migrated to the heart, as indicated by similar overall worm
      recoveries at 119 (mean 59.0%) and 140 days (mean 65.8%). Some worms remained in
      the tissues even at day 140. The third and fourth molts occurred as early as days
      3 and 56, respectively. On day 91, i.e., soon after the worms reached the heart,
      the mean lengths of males and females were 58.8 mm (range 43.0-75.0 mm) and 63.3
      mm (range 55.0-69.0 mm), respectively. At 140 days, male and female worms from
      the heart measured 118 mm (range 62.0-146.0 mm) and 144 mm (range 105.0-168.0
      mm), respectively.

PMID- 8158468
TI  - Epidemiology of Hymenolepis nana infections in primary school children in urban
      and rural communities in Zimbabwe.
AB  - Fecal specimens were obtained on 3 occasions at 10-12 wk intervals from 315
      children in 3 rural villages in Zimbabwe and from 351 children in the high
      density suburbs of an adjacent small town. Specimens were examined qualitatively
      and quantitatively for eggs of Hymenolepis nana, and these were found in 142
      (21%) children. Infections occurred more frequently in younger children in the
      urban area but in older children in rural areas. The prevalence in urban areas
      (24%) was higher than in rural areas (18%), and in urban areas infection
      correlated with low "hygiene scores" (determined by observation) and with the
      presence in the household of an infected sibling. The prevalence of infection in
      the 3 rural communities did not correlate with availability of water, number of
      households per toilet, with low "hygiene scores," or with the presence of an
      infected sibling. Treatment with a single oral dose of 15 mg/kg praziquantel
      cured 84% of the infected children. New or reinfections occurred more frequently
      in households that had an infected sibling in an urban but not rural setting. The
      study demonstrates distinct differences in the transmission of H. nana infection
      in rural and urban communities. The data suggest intrafamily transmission in
      urban areas, particularly in households with poor hygiene behavior, leading to
      primary infection early in life. In rural areas, the prevalence of infection and
      the incidence of reinfection were highest in children of school age, and there
      was little evidence for intrafamily transmission of the parasite.

PMID- 8158469
TI  - Two new species and temporal changes in the prevalence of eimerians in a free
      living population of Townsend's ground squirrels (Spermophilus townsendii) in
      Idaho.
AB  - More than 1,180 fecal samples were collected from 253 juvenile and 384 adult
      Townsend's ground squirrels (Spermophilus townsendii) at the Snake River Birds of
      Prey Area near Boise, Idaho, from February to June 1992. Oocysts of 7 eimerians
      were observed. Five are new host records (Eimeria beecheyi, Eimeria bilamellata,
      Eimeria callospermophili, Eimeria lateralis, and Eimeria morainensis), 2 species
      are described here as new, and new structural information on E. morainensis is
      added. Sporulated oocysts of Eimeria adaensis n. sp. are ovoidal, 19.6 x 22.7 (16
      22 x 18-26) microns with sporocysts ellipsoidal 7.2 x 11.9 (6-10 x 9-15) microns.
      No micropyle or oocyst residuum, but polar bodies, Stieda bodies, and sporocyst
      residua are present. Sporulated oocysts of Eimeria pseudospermophili n. sp. are
      ovoidal, 24.7 x 28.5 (21-27 x 25-32) microns with sporocysts ellipsoidal 8.8 x
      14.2 (8-10 x 12-17) microns. Micropyle and oocyst residuum are absent, but polar
      bodies and Stieda bodies are present. Sporulated oocysts of E. morainensis are
      more variable in size and shape than originally described and contain 2
      distinctly different residua not previously described. Temporal changes in the
      prevalence of eimerians of all 7 species combined in adult squirrels showed
      significant decline (r2 = 0.79, P < 0.001). We hypothesize that this decline was
      due to drought during the period of squirrel activity. No significant temporal
      change in the prevalence of eimerians in juvenile squirrels was observed. The
      prevalence of E. callospermophili, E. adaensis, and all eimerians combined in
      adults was significantly greater than in juveniles.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8158470
TI  - Adherence of monocytes and polymorphonuclear cells to infective larvae of
      Strongyloides stercoralis after complement activation.
AB  - The activation of the complement system by living Strongyloides stercoralis
      filariform larvae and their antigenic preparation was demonstrated in vitro
      through both classical and alternative pathways. This activation does not require
      the presence of specific antibodies but promotes the adhesion of peripheral blood
      monocytes (MNC) and polymorphonuclear cells (PMNC) to the larval surface. Larvae,
      totally coated by PMNC, showed a visible loss of motility after 2 hr incubation.
      Ethylenediamine tetraacetic acid, in contrast to ethylene glycol-bis beta
      aminoethylether N,N,N,N-tetraacetic acid, abolished the adherence activity,
      suggesting the involvement of the alternative pathway in this process. Deposition
      of complement components C1q, C3, C4, C8, and properdin on the larval surface was
      demonstrated by immunofluorescence assays. In addition, complement activation by
      the larvae was demonstrated through C3 conversion and C4 cleavage assays, both
      depending on the number of larvae. On the other hand, complement activation by S.
      stercoralis antigen was determined by factor B and C4 cleavage, as well as C3
      conversion assays. Our results suggest that the complement system as a first line
      of defense, in association with the effector cells, plays an important role in
      the nonspecific immune response of the host to S. stercoralis infection,
      especially considering the constant parasite recycling through the host tissues.

PMID- 8158471
TI  - Electrophoretic and serological analysis of host antigens associated with the
      adult Schistosoma mansoni tegument.
AB  - One-dimensional and 2-dimensional (2-D) polyacrylamide gel electrophoresis and
      immunoblotting with various specific antisera were used to analyze host antigens
      eluted from the surface of adult male Schistosoma mansoni into culture medium
      following short-term incubation. Silver-stained sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) gels revealed 27 protein bands from
      the parasite culture medium (eluate), ranging from > 200 kDa to 25 kDa. Eight of
      these bands corresponded to whole mouse plasma protein bands that migrated to the
      same positions. Color silver-stained 2-D SDS-PAGE gels revealed 93 protein spots
      from the eluate; 32 of them corresponded with similar spots in a normal mouse
      serum 2-D SDS-PAGE gel. Eleven protein components of the eluate, ranging from >
      200 kDa to 25 kDa, reacted with anti-mouse whole serum antiserum. Specific
      antisera recognizing components in the parasite culture medium included those
      with specificity for each of the classes and subclasses of mouse immunoglobulin
      (except IgG and IgE), mouse albumin, and mouse alpha-2-macroglobulin. Specific
      antisera against murine erythrocytes, hemoglobin, the complement component C3,
      transferrin, fibronectin, fibrinogen, and the mouse major histocompatibility
      class I protein H-2Db heavy chain did not react with any eluate component.

PMID- 8158472
TI  - Peptides associated with monensin resistance in sporozoites of Eimeria tenella
      (Coccidia).
AB  - Resistance to monensin in the sporozoites of a laboratory strain (WIS) of Eimeria
      tenella was amplified by treating free sporozoites with increased monensin levels
      in vitro, followed by propagation of these treated sporozoites in chickens. The
      parent strain of WIS and its subsequent lines developed from the treatment of
      monensin at 1, 5, or 25 micrograms/ml were designated as WIS(0), WIS(1), WIS(5),
      or WIS(25), respectively. The penetration rate of sporozoites into primary
      chicken kidney cell cultures showed that the sensitivity of sporozoites to the
      treatment of monensin at 1 and 5 micrograms/ml was significantly reduced in the
      WIS(25) line in comparison with the WIS(0) line. When native polyacrylamide gel
      electrophoresis (PAGE) was conducted, a change in the relative mobility of a
      protein band was found in the protein samples of these coccidial lines. Sodium
      dodecyl sulfate PAGE revealed that 2 peptides with molecular weights of
      approximately 50.0 and 31.4 kDa were present in the sporozoites of resistant
      lines but undetectable in their WIS-parent sporozoites. Derivation of the
      resistant lines from a drug-sensitive parent line gave strong support to a link
      between the appearance of the peptides and resistance to ionophores in this
      strain of E. tenella.

PMID- 8158473
TI  - A standardized method for the in vivo maintenance of Cryptocaryon irritans
      (Ciliophora) using the grey mullet Chelon labrosus as an experimental host.
AB  - Experimental primary infections with Cryptocaryon irritans were successfully
      established in mullet following exposure to theronts and maintained for up to 34
      successive cycles in this host. Fish were exposed to measured numbers of theronts
      collected within 4 hr of excystment. Free-swimming trophonts and reproductive
      cysts were maintained in wells of tissue culture plates containing sterilized
      seawater and subjected to a photoperiod of 12 hr light:12 hr dark. Excystment was
      found to be asynchronous over a period from 84 hr to 35 days. The procedure
      provided at least a 10-fold yield of parasite material per cycle of transmission.

PMID- 8158474
TI  - Hematologic characteristics of avian malaria cases in African black-footed
      penguins (Spheniscus demersus) during the first outdoor exposure season.
AB  - Twenty-nine juvenile, captive-reared African black-footed penguins (Spheniscus
      demersus) were hematologically monitored every 2 wk over the period of 24 wk
      during their first outdoor exposure. Blood samples taken from the penguins were
      screened for 12 blood evaluation parameters. Parasitemic penguins were medically
      treated. Eighteen birds (62.1%) experienced naturally acquired malaria and 11
      birds (37.9%) remained nonparasitemic. A total of 32 avian malaria episodes were
      noted; 25 (78.1%) were identified as Plasmodium elongatum, 5 (15.6%) as
      Plasmodium relictum, and 2 (6.3%) as Plasmodium spp. One P. elongatum (3.4%) and
      3 P. relictum (10.3%) infections were fatal. All deaths occurred during the first
      episode of parasitemia. Gross lesions of the birds that died included
      hepatomegaly and splenomegaly. Interstitial pneumonia with schizonts was observed
      on histological examinations. The range, mean, and SD of 12 hematological
      parameters were determined for nonparasitemic and parasitemic penguins.
      Differences between these groups in total white blood cell (WBC) counts and
      relative lymphocytosis (LYMPHS) were not significant. The combined classes of
      total WBC counts (> 20.0 x 10(3)/microliters) and LYMPHS (> 60.0%) are not
      indicative of avian malaria infection in African penguins. No correlations were
      found between changes in the values of blood parameters with season or age of
      penguins. Treatment of parasitemic birds significantly reduced expected mortality
      from 50.0% to 13.8%.

PMID- 8158475
TI  - Echinobreviceca coelorhynchae n. gen., n. sp. (Echinobrevicecinae n. subf.), a
      fellodistomid from Coelorhynchus coelorhynchus (Macrouridae) from the Gulf of
      Mexico.
AB  - During a study of digenean parasites of deep sea fishes from the Gulf of Mexico,
      38% (5 of 13) of Coelorhynchus coelorhynchus Risso, 1810, (Macrouridae) were
      infected with a total of 33 specimens (6.6/infected fish) of an undescribed
      species of Fellodistomidae representing a new genus and subfamily. Other
      macrourids collected at the same time (Bathygadus macrops Goode and Bean, 1886,
      Malacocephalus occidentalis Goode and Bean, 1885, and Nezumia aequalis Gunther,
      1878) were not infected with Echinobreviceca coelorhynchae n. gen., n. sp. The
      new species is most similar to members of the subfamily Baccigerinae, but differs
      in having an I-shaped excretory vesicle, a densely spined tegument, a
      pretesticular ovary, and a blind seminal receptacle. Echinobrevicecinae n. subf.
      is separated from other subfamilies in the family by having an I-shaped excretory
      vesicle. Echinobreviceca n. gen. is established as the type and only genus in the
      new subfamily, and E. coelorhynchae n. sp. as the only known species in the
      genus.

PMID- 8158476
TI  - Coronocyclus ulambajari n. sp. (Nematoda: Strongyloidea) from horses of Mongolia.
AB  - Coronocyclus ulambajari n. sp. (Strongyloidea: Cyathostominae) from horses of
      Mongolia is described. The external leaf-crown (ELC) of the new species consists
      of 28 elements and the internal leaf-crown (ILC) of approximately 80 elements. A
      spindle-shaped (in optical section) mouth collar support is separated anteriorly
      from the buccal capsule and connected to it and elements of leaf-crowns by
      bundles of connective tissue. The buccal capsule is cylindrical, circular in
      cross-section, and approximately 3 times as wide as deep. A large, tongue-like
      dorsal cone protrudes from the floor of the buccal capsule overlying the large
      dorsal esophageal tooth. The duct of the dorsal esophageal gland opens at the tip
      of the dorsal cone. The tail and vagina of females are short, and the vulva is
      close to the anus. The buccal capsule and dorsal cone are most similar to
      Coronocyclus labratus, but differ significantly in size of dorsal cone and
      relative width and depth of the buccal capsule as well as characteristics of the
      leaf-crowns and female reproductive systems.

PMID- 8158477
TI  - Choanotaenia atopa n. sp. (Cestoda: Dilepididae) from a domestic cat in Kansas.
AB  - Choanotaenia atopa (Cestoda: Dilepididae) is described (host: domestic cat from
      the vicinity of Manhattan, Kansas); its natural host is presumed to be a rodent.
      Choanotaenia atopa is morphologically similar to cestodes of 6 species, all from
      rodents, formerly placed in the genus Rodentotaenia Matevosian, 1953, and
      subsequently removed to the genera Choanotaenia Railliet, 1986, or Monopylidium
      Fuhrmann, 1899. The systematic position of those cestodes is discussed;
      Monopylidium and Rodentotaenia are treated as synonyms of Choanotaenia.
      Choanotaenia atopa is distinguished by size and form of rostellar hooks,
      regularly alternating genital pores, and other characters in genital organs.

PMID- 8158478
TI  - The effect of treating beef cattle on pasture with ivermectin on the prevalence
      and intensity of Thelazia spp. (Nematoda: Thelazioidea) in the vector, Musca
      autumnalis (Diptera: Muscidae).
AB  - Trihedron sticky traps were used to monitor the prevalence and intensity of
      Thelazia spp. in face flies associated with 2 groups of cattle. Traps were set
      for 24 hr once a week beginning 2 wk before cattle were turned out to pasture
      following winter housing and continued until flies reached diapause in October.
      The 50 heifers in group 1 received 1 treatment with ivermectin (Ivomec Pour-On
      for cattle, 500 micrograms/kg body weight) on the day of turnout onto pasture.
      The 50 cows and their calves in group 2 were not treated. Treating cattle with
      ivermectin delayed the onset of infection in Musca autumnalis by 20 days and
      reduced the prevalence to 2.2% compared to 26.9% in flies from the control
      pasture. Although residues of ivermectin eradicate many fly larvae developing in
      cattle feces, there was no significant difference in the number of flies counted
      on the faces of cattle or in the number of flies caught on sticky traps on the 2
      pastures (P > 0.05).

PMID- 8158479
TI  - Ultrastructure of the human skeletal muscle sarcocyst.
AB  - The ultrastructure of the human skeletal muscle sarcocyst found in Malaysia is
      reported. Sarcocyst-positive, formalin-fixed tongue tissues were postfixed in
      osmium tetroxide. The primary cyst wall consisted of a thin membrane supported by
      osmiophilic material that was interrupted regularly by vesicle-like
      invaginations. Although there were no cytophaneres, stubby protrusions of the
      primary wall were observed. These protrusions were accentuated by dense,
      curvilinear material externally. The primary wall was wavy over about half the
      cross section of the cyst. The granular ground substance underlying the primary
      wall occasionally contained hitherto undescribed coiled microtubular structures.
      Branching septa extended from the ground substance into the cyst, separating
      mature merozoites into compartments. A few peripheral metrocytes and many
      laminated myelin figure-like structures, probably degenerating merozoites, were
      found. Although the human muscular sarcocyst has the same basic ultrastructure as
      those found in other animals, the stubby protrusions and coiled microtubular
      structures in the ground substance have not been described previously in nonhuman
      animals.

PMID- 8158480
TI  - Occurrence and distribution of the parasitic copepod Leposphilus labrei on
      corkwing wrasse (Crenilabrus melops) from Mulroy Bay, Ireland.
AB  - Corkwing wrasse (Crenilabrus melops: Labridae), used to control ectoparasites on
      sea-farmed salmon, were found to contain the copepod parasite Leposphilus labrei
      (Philichthyidae) within the lateral line. Prevalence was 30.7% in 6,270 wrasse
      examined from Mulroy Bay, Ireland. Significantly more males than females or
      juveniles were infected; this appears related to size at age, as prevalence
      increases above 100 mm total length. Intensity was normally unity and the
      parasite showed a significant preference to infect the left rather than the right
      side of male wrasse. It is suggested that this preference is due to asymmetric
      fish locomotion, equivalent to "handedness."

PMID- 8158481
TI  - Microbesnoitia leoni Bwangamoi, 1989, from the African lion (Panthera leo)
      redetermined as a junior synonym of Hepatozoon canis (James, 1905) Wenyon, 1926.
AB  - Hepatozoon canis-like schizonts were found in the hearts of 2 lionesses (Panthera
      leo) from Kenya. The parasite, initially described as a new genus and new species
      Microbesnoitia leoni Bwangamoi, 1989, is determined to be a junior synonym of
      Hapatozoon canis (James, 1905) Wenyon, 1926.

PMID- 8158482
TI  - Respiratory cryptosporidiosis in a bovine.
AB  - Intestinal cryptosporidiosis has been extensively studied in young calves, but
      respiratory invasion by Cryptosporidium in these animals has, surprisingly, not
      been investigated. In the present study the parasite was observed in lung tissue
      of a calf, using light and electron microscopy. This demonstrates that
      Cryptosporidium can develop in the bronchial epithelium in bovines.

PMID- 8158483
TI  - High performance thin-layer chromatographic analysis of sugars in Biomphalaria
      glabrata (Gastropoda) infected with Echinostoma caproni (Trematoda).
AB  - High performance thin-layer chromatographic analysis was done on the hemolymph
      and digestive gland-gonad complex (DGG) of Biomphalaria glabrata snails
      experimentally infected with the intramolluscan stages of Echinostoma caproni.
      The major sugars detected in both the DGG and hemolymph of infected and
      uninfected snails were glucose and trehalose. Quantitative analysis by scanning
      densitometry showed a significant reduction in glucose in both the hemolymph and
      DGG of infected snails at 4, 6, and 8 wk postinfection. A similar analysis on
      trehalose showed that this sugar was significantly reduced at 6 wk postinfection
      in the hemolymph and DGG of infected snails and could not be detected from these
      sites in infected snails by 8 wk postinfection. Findings from this study were
      compared with information on sugars in B. glabrata infected with larval stages of
      Schistosoma mansoni.

PMID- 8158484
TI  - Patent gut infections in immunosuppressed adult C57BL/6N mice following
      intraperitoneal injection of Cryptosporidium parvum oocysts.
AB  - Two experiments were conducted to determine if intraperitoneal (i.p.) and/or
      subcutaneous (s.c.) injection of Cryptosporidium parvum oocysts could produce
      patent gut infections in dexamethasone (DEX) or dexamethasone phosphate (DEXp)
      immunosuppressed adult female C57BL/6N mice. The results from experiment 1 were
      suggestive but did not unequivocally demonstrate that i.p. injection of oocysts
      could produce patent gut infections in these mice. In experiment 2, all mice were
      individually caged, immunosuppressed with DEXp (groups 1 and 2) or DEX (groups 3
      and 4), and administered C. parvum oocysts either by orogastric intubation
      (groups 1 and 3), i.p. (group 2), or s.c. (group 4). All but 1 mouse in groups 1
      and 3 began shedding oocysts in their feces on day 3 post-infection (PI). Mice in
      these 2 groups continued to shed oocysts until they were killed on day 17 PI.
      Mice administered oocysts s.c. did not shed oocysts. In group 2, 1 mouse died, 1
      failed to shed oocysts, and 1 began shedding oocysts on day 3 PI. The remaining 5
      mice started shedding oocysts on either days 8, 10, or 14 PI and continued to
      shed oocysts until they were killed. We conclude that immunosuppressed adult
      C57BL/6N mice administered oocysts i.p. can develop patent gut infections with C.
      parvum.

PMID- 8158485
TI  - Cloning and sequence analysis of the small subunit ribosomal RNA gene from
      Nematodirus battus.
AB  - The small subunit ribosomal RNA gene (SSU rRNA) from the nematode parasite,
      Nematodirus battus, was cloned from amplified genomic DNA using polymerase chain
      reaction primers complementary to the 5' and 3' ends of Haemonchus contortus
      small subunit ribosomal DNA (SSU rDNA). The 1,758 base pair cloned fragment was
      sequenced in both directions using internally generated primers and aligned with
      those from the genus Haemonchus. Results indicated a 1.9% sequence difference
      between the genera with a 14.2% difference between N. battus and Caenorhabditis
      elegans. Data presented here in conjunction with previously published work
      comparing rDNA sequences within the genus Haemonchus demonstrate limited
      divergence in this group of genes between these subfamilies and suggest further
      that this molecule alone may be inappropriate for assessing phylogenetic
      relatedness within the superfamily Trichostrongyloidea.

PMID- 8158486
TI  - Clinical preventive services--where do PNPs stand?

PMID- 8158487
TI  - Health care reform and the nurse practitioner.

PMID- 8158488
TI  - Shaken baby syndrome: identification and prevention for nurse practitioners.
AB  - Shaken baby syndrome is a less widely recognized form of physical child abuse. It
      is defined as vigorous manual shaking of an infant who is being held by the
      extremities or shoulders, leading to whiplash-induced intracranial and
      intraocular bleeding and no external signs of head trauma; often identifying
      shaken baby syndrome is difficult because of the lack of obvious external signs.
      Shaken baby syndrome should be considered in infants with seizures, failure to
      thrive, vomiting associated with lethargy or drowsiness, respiratory
      irregularities, coma, or death. With the increased awareness of child abuse, more
      attention has been focused on morbidity and death caused by the violent shaking
      of infants. This article describes the clinical findings of shaken baby syndrome,
      explores the characteristics of families at risk for abuse, and discusses
      implications for nurse practitioners.

PMID- 8158489
TI  - Conceptual underpinnings of the family support movement.
AB  - In communities across the nation, rapid expansion of programs seeking to promote
      healthy development of children by strengthening families has been taking place.
      These diverse programs are reshaping traditional approaches to families and
      children and are becoming important catalysts for change in human service
      delivery systems. Historically rooted in our culture and past initiatives, the
      family support movement is grounded in theories of the ecology of human
      development and social support. As popularity for these programs grows,
      preserving the underlying values and operating principles of family support is
      essential. Pediatric nurse practitioners can be strong advocates for these
      principles within their communities and health care settings.

PMID- 8158490
TI  - Visual clues to diagnosis of birth defects and genetic disease.
AB  - Congenital defects and inheritable diseases are a leading cause of childhood
      morbidity and death. Often these conditions have associated visual diagnostic
      clues that lead the clinician to a diagnosis and thus earlier preventive
      treatment of associated complications. Pediatric nurse practitioners can broaden
      their visual senses by reviewing pictorial compendiums of pediatric disease to
      gain experience in visual recognition and having a keen eye while examining
      patients. This article identifies by category and pictorial illustration several
      birth defects and genetic disorders that are readily identified by observation.
      Even minor anomalies may portend significant underlying internal problems.

PMID- 8158491
TI  - The pediatric nurse practitioner as case manager in the delivery of services to
      children with heart disease.
AB  - Today's health care environment prompted implementation of a case management
      model by pediatric nurse practitioner clinical nurse specialists to promote the
      organization of resources for optimal care of children with heart disease.
      Evaluation of this pilot program suggests that achievement of expected outcomes
      within an appropriate length of stay was facilitated, that parents were ready for
      discharge, and that readmissions were infrequent. In addition, patient and system
      variances resulting in delay of discharge and discharge preparation needs were
      identified. The pediatric nurse practitioner as case manager may have a
      significant impact on the quality and cost of care for hospitalized children.

PMID- 8158492
TI  - Grandparenting: benefits and problems.

PMID- 8158493
TI  - Colony-stimulating factors: use in the pediatric population (Part I).

PMID- 8158494
TI  - Is this sexual abuse?

PMID- 8158495
TI  - "All politics is local"--creative suggestions for advocacy at the local level.

PMID- 8158496
TI  - Sun protection.

PMID- 8158497
TI  - Local delivery of prostaglandin E1 induces periodontal regeneration in adult
      dogs.
AB  - Formation of cementum, alveolar bone and periodontal ligament was produced in 18
      sites on buccal surfaces of mandibular premolars and molars of 11 adult dogs near
      to sites of local delivery of prostaglandin E1 (PGE) for three weeks.
      Mineralizing bone and cementum were labelled with fluorescent dyes and polarizing
      microscopy showed periodontal ligament fibers between these new mineralized
      tissues. These observations extend recent demonstrations that local application
      of PGE causes formation of new bone on the mandible and suggest the potential for
      predictable, site-directed periodontal regeneration.

PMID- 8158498
TI  - Chemoluminescence generation and MTT dye reduction by polymorphonuclear
      leukocytes from periodontal disease patients.
AB  - Alterations of polymorphonuclear leukocytes (PMNs) functions have been reported
      in patients with severe forms of some periodontal disease. In this study we
      evaluated the chemoluminescence generation and MTT dye reduction by human PMN in
      patients with juvenile periodontitis (JP), rapidly progressive periodontitis
      (RPP) and adult periodontitis (AP) during protein kinase C (PKC) activation or
      during the phagocytosis of opsonized zymosan. The results demonstrated that only
      PMNs of JP patients showed a decreased chemoluminescence generation and MTT dye
      reduction during the phagocytosis of opsonized zymosan (p < 0.05). The time to
      reach the maximal peak during the PKC activation on the chemoluminescence
      reaction was evaluated and JP PMNs patients demonstrated a depressed value (7.0
      +/- 0.4 min) compared with healthy volunteers (13.8 +/- 0.5 min). The etiology
      and importance of such cellular alterations in the immunopathogenesis of the
      periodontal disease are discussed.

PMID- 8158499
TI  - Inhibitory effect of aspirin on root resorption induced by mechanical injury of
      the soft periodontal tissues in rats.
AB  - The purpose of the present study was to study histologically and histometrically
      the inhibitory effect of aspirin on root resorption induced by mechanical injury
      of the periodontal soft tissues in rats. Resorption lacuna in the root surface of
      the molar in animals given both mechanical injury and aspirin administration
      contained fewer odontoclasts and was smaller in length and area than that in
      animals given only mechanical injury. The result of the present investigation
      indicated that the administration of aspirin might suppress root resorption
      induced by mechanical injury of the periodontal soft tissues.

PMID- 8158500
TI  - Immunolocalization of matrix metalloproteinases and TIMP-1 (tissue inhibitor of
      metalloproteinases) in human gingival tissues from periodontitis patients.
AB  - The matrix metalloproteinases (MMPs) collagenase, gelatinase A (72 kDa
      gelatinase), stromelysin, and their specific inhibitor TIMP-1 (tissue inhibitor
      of metalloproteinases), were immunolocalized using specific polyclonal antisera
      in gingival tissues from 21 patients with chronic inflammatory periodontal
      disease. Monoclonal antibodies against macrophages (Leu-M5), B cells (Leu-14),
      helper T cells (OKT4), suppressor T cells (OKT8) and the HLA-DR epitope were also
      used to identify leukocyte subsets. MMPs were observed in connective tissues at
      sites that histologically showed signs of remodelling. The number and
      distribution of positive cells varied widely, however, not only between
      individual biopsy specimens, but also within the same specimen. The same was true
      for the composition and distribution of the inflammatory cell infiltrate.
      Moreover, although there was a positive correlation between the number of MMP
      producing cells and the severity of inflammation in some specimens, for others
      with comparable leukocyte subset scoring the number was reduced and sometimes
      absent altogether. Cells secreting MMPs were fibroblasts, macrophages and
      epithelial cells. It was not possible to determine unequivocally whether a MMP
      positive cell within the connective tissue was a fibroblast or a macrophage,
      since the antisera recognise both fibroblast and macrophage MMPs and the
      different fixation requirements for MMPs (4% paraformaldehyde) and Leu-M5
      (acetone) precluded co-localization on the same section. TIMP-1 was
      immunolocalized within connective tissue cells at sites of tissue remodelling.
      Our results support the hypothesis that tissue-derived MMPs may be involved in
      tissue remodelling in periodontal disease and conclusively demonstrate that
      epithelial cells may be involved as well as connective tissue cells.

PMID- 8158501
TI  - Role of cytokines in the modulation of neutrophil chemotaxis in localized
      juvenile periodontitis.
AB  - Decreased neutrophil chemotaxis has been implicated in the pathophysiology of the
      disease, localized juvenile periodontitis (LJP). The biological basis for the
      altered neutrophil function in LJP has been suggested to be an intrinsic cellular
      defect, involving a decrease in the number of N-formyl-methionyl-leucyl
      phenylalanine (FMLP) receptors on the cell surface. We have investigated the
      relative contribution of serum-borne factors in the modulation of neutrophil
      functions in LJP, in a large population of LJP patients and healthy control
      subjects (HS). Treatment of HS-neutrophils with LJP-sera, resulted in a decreased
      neutrophil chemotactic response, and down regulation of FMLP receptors on the
      cell surface. Pretreatment of LJP-sera with anti-TNF and anti-IL-1 antibodies
      effectively, although incompletely, neutralized the ability of LJP-sera to
      modulate chemotaxis and FMLP receptor levels in HS-neutrophils. The changes
      induced by LJP sera were specific and sustained and could not be reversed by
      placing LJP-serum treated neutrophils in HS-serum. Sera obtained from HS and
      patients with adult periodontitis (AP), both of which exhibit normal chemotaxis,
      and patients with clinically diagnosed LJP with normal neutrophil chemotaxis (LJP
      nctx) did not modulate HS neutrophil chemotaxis or FMLP receptors. Furthermore,
      recombinant human TNF-alpha, rhIL-1 alpha and rhIL-1 beta, at very low
      concentrations (15 pg/ml to 150 pg/ml), modulated the chemotactic response as
      well as FMLP receptor numbers on HS-neutrophils, in a manner similar to those
      observed in LJP. The present findings demonstrate that the biologic basis for the
      altered neutrophil function may not be an intrinsic cellular defect in
      neutrophils, but at least in part due to quantitatively small but biologically
      significant elevations in the levels of TNF-alpha and IL-1 in the serum.

PMID- 8158502
TI  - Improvement of gingival and alveolar bone status in periodontitis-affected
      hamsters treated with 15-methyl prostaglandin E1.
AB  - Exogenous PGE1 at pharmacological doses suppresses acute and chronic inflammation
      manifestations. As periodontitis possesses features of both acute and chronic
      inflammation, attenuation of periodontal destruction in hamsters was attempted by
      using 15-M-PGE1, a stable PGE1 analog. The agent was tested at 2 different doses
      (100 and 150 micrograms/kg/d) and its effects were matched against disease-free
      and periodontitis-affected animals. No effect was found with the 100 micrograms
      regimen. In contrast, in the 150 micrograms group, in the gingiva around the
      first right mandibular molar the pocket epithelium and infiltrated connective
      tissue (ICT) areas, the mean vascular lumen, the number of PMNLs adherent to
      blood vessels and infiltrating the ICT were significantly reduced. The number of
      osteoclasts was markedly diminished as well, but their intrinsic activity was
      enhanced. Bone formation was totally inhibited in this treatment group. These
      results indicated that 15-M-PGE1 effectively improved gingival inflammation
      mostly by reducing edema and PMNL recruitment and controlled alveolar bone
      destruction by reducing the osteoclast recruitment. From a therapeutic point of
      view the complete inhibition of formation seems to contraindicate its use.

PMID- 8158503
TI  - Cellular origins and differentiation control mechanisms during periodontal
      development and wound healing.
AB  - In the context of cellular origins, odontogenic epithelium and oral epithelium
      are the sources for junctional epithelium during development and during wound
      healing respectively. In contrast, both odontogenic and non-odontogenic
      mesenchyme contain the progenitors for gingival fibroblasts in developing tissues
      while in wounded tissues, gingival fibroblasts are derived from gingival
      connective tissues and comprise a heterogeneous population of cells with diverse
      properties and functions. Periodontal ligament, bone and cementum cell
      populations apparently originate from dental follicle progenitor cells during
      development, but during wound healing derive from ancestral cells in periodontal
      ligament and bone. Cellular differentiation in developing periodontium is
      governed in part by epithelial-mesenchymal interactions that generate specific
      signals which regulate selective cell populations in time and space. On the other
      hand, differentiation during wound healing and regeneration is regulated by a
      vast array of extracellular matrix informational molecules and by cytokines that
      induce both selective and non-selective responses in the different cell lineages
      and their precursors. Further, several important signalling systems are
      irretrievably lost after development is complete. Thus, in the context of
      cellular origins and differentiation, developing and wounded periodontal tissues
      exhibit fundamental differences. Future prospects for improved healing and
      regeneration of periodontal tissues may derive from identification and isolation
      of informational molecules that are stored in connective tissue matrices. These
      molecules and elucidation of their functions may open new perspectives in our
      understanding of the biology of periodontal wound healing and may provide novel
      approaches to periodontal regeneration.

PMID- 8158504
TI  - Influence of contrast enhancement and pseudocolor transformation on the diagnosis
      with digital subtraction images (DSI).
AB  - This study evaluated the influence of the image processing step of digital
      subtraction images on inter- and intraexaminer agreement in the interpretation of
      alveolar bone changes. 52 pairs of standardized radiographs from various clinical
      trials were included. Six dentists were invited to interpret the images projected
      as slides in random order. Display one demonstrated the slide of the digitized
      baseline radiograph and the follow-up image. Display two showed the regular
      digital subtraction image. Display three represented a grey level contrast
      enhanced version and displays four and five were pseudo/color enhanced
      subtraction images. Applying kappa-statistics and multiple regression analysis it
      was demonstrated that better agreements were obtained when the two color coded
      displays of subtraction images were shown to the interpreters. The image
      interpretation was performed in two series. For the first evaluation the
      interpreters were not informed about the therapy provided nor the time elapsed
      between taking the pairs of standardized radiographs. In the second series this
      information was provided. It could be demonstrated that the agreement in the
      diagnosis of bone change was less influenced by the knowledge about the clinical
      information if the two color-converted versions of subtracted images were
      evaluated. Thus, it was concluded that image processing of subtraction images
      using color enhancement might improve agreement in the diagnostic task. The color
      coded images were less influenced by the bias in the interpretation of an
      expected change. The decision making process might be more objective when using
      color enhanced subtraction images.

PMID- 8158505
TI  - Probing velocity: novel approach for assessment of inflamed periodontal
      attachment.
AB  - Little is known about the biophysical characteristics of the dento-gingival
      junction in response to the development or resolution of inflammation. The
      Toronto automated periodontal probe (TAPP) provides an estimate of the
      biophysical integrity of the dento-gingival junction by measuring intrapocket
      probing velocity. Presence or absence of a plateau in displacement versus time
      plots were used to perform dichotomous analyses as a function of established
      parameters of inflammation. Plateaus were operationally defined as a 3 standard
      deviation reduction in the slope of the displacement versus time plot (probing
      velocity) and hence the plateau represents an increased resistance of the probe
      tip at the dento-gingival junction. The aim of the study was to measure the
      relationship between post-treatment reductions of gingival inflammation and the
      probability of plateau formation as measured by the TAPP. Twenty-nine subjects
      exhibiting gingival inflammation were provided with periodontal therapy
      consisting of subgingival scaling and root planing. Over a 2-month sampling
      period, 6 sites from each subject were monitored and these sites exhibited wide
      variations of inflammation. Logistic regression revealed a significant
      relationship between the probability of plateau formation and treatment (P =
      0.002), plaque index (P = 0.002), the increased severity levels of gingival index
      (P > 0.05), or bleeding index (P > 0.05). The probability of plateau formation
      decreased with higher levels of crevicular fluid flow but there was no dependence
      of plateau formation on probing depth (P > 0.55). These data indicate a direct
      relationship between improved measures of clinical health and increased
      resistance to probe penetration near the base of the pocket.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8158506
TI  - Chlorhexidine use after two decades of over-the-counter availability.
AB  - Chlorhexidine (CHX) is a compound with plaque-inhibiting effects and available
      only by prescription in the United States. In Norway, however, CHX has been
      dispensed over-the-counter for over 20 years, and this study was undertaken to
      evaluate dentists' perceptions regarding its indications, usefulness, and side
      effects. A written questionnaire was sent to a sample of 10% of dentists
      registered in Norway, 78% of whom (354) responded. Additionally, representatives
      from 2% of all dental practices in Norway were contacted by telephone. Fourteen
      percent (14%) of the respondents reported that they never recommended CHX to
      their patients. Among those recommending the compound, 85% used it frequently
      after surgical periodontal procedures; 74% when treating acute gingivitis; 57%
      following oral surgery in general; and 35% during non-surgical periodontal
      therapy. It was used also as an adjunct to other treatment routines. Seventy
      three percent (73%) reported frequent use of CHX when treating stomatitis and 54%
      in herpes simplex infections. As to side effects, 77% of the dentists indicated
      that staining of teeth, restorations, and the tongue was a major concern to
      patients; 12% reported inconveniences due to the bitter taste; and 6% reported
      other disturbances such as dryness of the mouth and development of oral
      ulcerations. The majority (94%) of the dentists recommended mouth rinsing,
      whereas 6% recommended a gel form. Only 4% of the dentists recommended rinsing
      with a patient-diluted 0.1% concentration, whereas 96% recommended the standard
      0.2% formulation; 88% recommended using CHX mouthwash twice a day or more
      often.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158507
TI  - Dentine hypersensitivity: a clinical trial to compare 2 strontium densensitizing
      toothpastes with a conventional fluoride toothpaste.
AB  - A considerable number of varied agents are apparently effective in the treatment
      of dentine hypersensitivity. In particular, the literature supports the efficacy
      of fluoride and strontium containing formulations. Despite this, comparisons
      between strontium products are relatively few in number and surprisingly there
      are almost no evaluations of these products against "bench mark," conventional
      commercial fluoride toothpastes. This study was a double-blind parallel group
      comparison of two strontium-based desensitizing toothpaste products and a
      conventional fluoride product in the treatment of dentine hypersensitivity. A
      total of 119 patients completed the 12-week study and from them, sensitivity
      gradings were obtained at baseline, 1, 4, 8, and 12 weeks. Sensitivity was scored
      in response to cold air, a thermal probe at 0 degree C, and scratching with a
      dental probe. Patients also graded their overall sensitivity at each visit, using
      a visual analogue scale and the effects of treatment on completion. Plaque and
      gingivitis indices were recorded at each visit. There was an overall and
      progressive reduction in all sensitivity parameters in the 3 groups with no
      significant differences between the treatments. Plaque and gingivitis scores were
      already relatively low in this patient group at baseline but improved further as
      the study continued. The improvements, however, were comparable in the 3 groups.
      Under the conditions of this clinical trial the 2 desensitizing toothpastes
      showed similar reductions, but no greater than that observed in the conventional
      fluoride toothpaste. There is perhaps the need for further evaluations of
      desensitizing formulations using conventional fluoride products as controls
      rather than minus active or placebo formulations.

PMID- 8158508
TI  - Longitudinal evaluation of elastase as a marker for the progression of
      periodontitis.
AB  - To determine whether elastase levels in gingival crevicular fluid (GCF) could
      serve as a marker for the progression of periodontitis, we monitored GCF elastase
      and periodontal status in selected sites in 32 periodontally healthy volunteers
      and 31 periodontitis patients at intervals over a 6-month period. Clinical
      measurements included plaque index, gingival index, bleeding on probing,
      suppuration, probing depth, clinical attachment level, and relative attachment
      level measured with an automated disk probe. GCF elastase, detected by reaction
      with a fluorescent substrate, was assessed visually against fluorescence
      standards and quantitatively with a fluorometer. Bone loss was detected by
      subtraction radiography of standardized vertical bite-wing radiographs at
      baseline and 6 months. Mean visual elastase scores (VES) and quantitative
      elastase measurements were significantly higher (P < 0.001) in sites from
      periodontitis patients than in sites from healthy volunteers. When bone loss was
      used as the criterion for disease progression, significantly higher (P < 0.001)
      visual and quantitative GCF elastase levels were found at progressing sites than
      in nonprogressing sites in the periodontitis patients. The odds ratios (OR) for
      the event of developing bone loss with positive 4-minute and 8-minute VES tests
      were 4.2 (P < 0.001) and 7.4 (P < 0.001), respectively. When corrected for the
      tendency of progressing sites to be clustered within a subpopulation of patients,
      the OR for developing bone loss with the 4-minute and 8-minute VES tests were 3.1
      (P < 0.007) and 4.9 (P < 0.001), respectively. These data indicate that sites
      with high levels of elastase are at significantly greater risk for progressive
      bone loss as assessed by digital subtraction radiography.

PMID- 8158509
TI  - Priming effect of Porphyromonas gingivalis lipopolysaccharide on superoxide
      production by neutrophils from healthy and rapidly progressive periodontitis
      subjects.
AB  - Pre-incubation of neutrophils from rapidly progressive periodontitis (RPP)
      patients with lipopolysaccharide (LPS) extracted from Porphyromonas gingivalis
      was found to prime the neutrophils for enhanced FMLP-stimulated superoxide
      production in a dose-dependent manner. The priming effect of P. gingivalis LPS on
      neutrophils from control subjects was scanty or without effect at all. Inclusion
      of human serum in the experimental priming conditions increased the control and
      RPP neutrophil response by 2 to 3 fold. Blocking of the CD14 receptor on the
      neutrophil surface with monoclonal antibody eliminated the priming effect.
      Furthermore, incubation of control neutrophils with P. gingivalis LPS in the
      presence of serum from RPP patients generated a higher response as compared to
      incubation with control serum. The data suggest that neutrophil priming described
      in RPP patients is dependent on a serum factor which alters the neutrophil
      response to priming agents such as LPS.

PMID- 8158510
TI  - The secretion of PGE2, IL-1 beta, IL-6, and TNF alpha by adherent mononuclear
      cells from early onset periodontitis patients.
AB  - The secretion of prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF
      alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) by adherent
      mononuclear cells (AMNC) from 28 patients with early-onset periodontitis was
      studied. The early onset-periodontitis patients consisted of 12 patients with
      localized juvenile periodontitis (LJP) and 16 patients with severe generalized
      periodontitis (SGP). The AMNC responses to different concentrations of
      lipopolysaccharide (LPS) (E. coli) were determined in these 28 patients and
      compared to 14 healthy controls. Mediator levels in the supernatant were measured
      using radioimmunoassays for PGE2, IL-1 beta, and IL-6 determination and an enzyme
      linked immunosorbent assay for TNF alpha levels. The mean age of the patients was
      19.9 years for the LJP group, 30.4 years for SGP, and 28.0 years for the
      controls. The mean number of teeth per patient with attachment loss of > 6 mm was
      4.75 in the LJP patients and 17.3 in the SGP group. In the absence of LPS, LJP
      AMNC secreted significantly more PGE2 than unstimulated control or SGP AMNC,
      while similar baseline amounts of IL-1 beta, IL-6, and TNF alpha were secreted by
      AMNC from the 3 patient groups. LPS stimulation resulted in the dose-dependent
      secretion of significantly higher levels of PGE2 by LJP AMNC compared to SGP AMNC
      which in turn secreted significantly more than controls. TNF alpha secretion by
      LJP monocytes was significantly greater than the SGP and the control groups while
      IL-1 beta secretion by the SGP AMNC was depressed compared to the other two
      patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158511
TI  - Assessment of interleukin-6 in the pathogenesis of periodontal disease.
AB  - This study was performed to investigate the aspects of interleukin-6 (IL-6)
      production in both the gingival tissue and the peripheral blood of patients with
      periodontal disease and of periodontally healthy subjects. In addition, IL-6
      expression in human gingival tissues was studied by reverse transcription
      polymerase chain reaction analysis and by immunoperoxidase staining with anti-IL
      6 monoclonal antibody. The levels of IL-6 in the culture supernatants from
      peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide and
      in serum were examined by bioassay. We detected IL-6 mRNA expression in all
      inflamed gingival tissues (17/17) examined and in 2/4 in healthy gingival
      tissues. IL-6 protein was detected mainly in endothelial cells, fibroblasts, and
      macrophages but not in the area containing T or B cells in the inflamed gingival
      tissues, and was not detected at all in healthy gingival tissues. There was no
      significant difference between the subjects with periodontal disease and those
      with healthy gingival tissues either in serum IL-6 levels or in the amount of IL
      6 produced by PBMC. These results suggest that non-lymphoid cells in inflamed
      gingival tissue may contribute to the pathogenesis of periodontal disease via IL
      6 production, and that the IL-6 produced in gingival tissue may not reflect the
      IL-6 levels in peripheral blood.

PMID- 8158512
TI  - Clinical, microbiological, and histological factors which influence the success
      of regenerative periodontal therapy.
AB  - The primary objectives of this double-blind, controlled clinical trial were to
      assess factor(s) which affect the success of guided tissue regeneration (GTR)
      procedures in mandibular Class II buccal furcation defects. Thirty subjects, with
      mandibular Class II furcation defects, were randomly assigned to one of two
      treatment groups; patients in Group A received oral hygiene instructions with
      scaling and root planing, while subjects in Group B received similar treatment
      but without subgingival scaling and root planing at the affected site. After
      initial oral hygiene instructions and scaling and root planing, GTR surgery was
      performed using ePTFE barrier membranes. Membranes were retrieved at 6 weeks and
      subjected to histological examination. Twelve months after regenerative therapy,
      clinical measurements and re-entry surgical measurements were repeated. Probing
      reduction (2.61 mm), horizontal probing attachment gain (2.59 mm), and vertical
      probing attachment gain (0.95 mm) were all significantly better compared to
      baseline. Likewise, significant improvements in furcation volume (8.0
      microliters) and in bone measurements were observed at re-entry. There was no
      discernible difference between subjects for whom complete anti-infective therapy
      was deferred to the time of the surgery (Group B) compared to subjects in whom
      complete anti-infective therapy was performed as part of the hygienic phase of
      therapy (Group A). Pre-operative pocket depth was directly correlated with the
      magnitude of attachment gain as well as the amount of new bone formation in the
      furcation area. Subjects who maintained good oral hygiene and who had minimal
      gingival inflammation throughout the study demonstrated consistently better
      regenerative response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158513
TI  - The influence of surface-free energy on supra- and subgingival plaque
      microbiology. An in vivo study on implants.
AB  - The influence of surface free energy on supra- and subgingival plaque
      microbiology was examined in 9 patients with functional fixed prostheses
      supported by endosseous titanium implants. Two abutments (trans-mucosal part of
      the 2 stage implant) were replaced by either a new titanium abutment or a fluor
      ethylene-propylene (FEP) coated abutment per subject. After 3 months of habitual
      oral hygiene, plaque samples were taken. Supragingival plaque was examined by
      means of differential phase-contrast microscopy, whereas for the subgingivial
      plaque additional analyses (DNA probes analysis, culturing) were performed. The
      subgingival samples were taken by paper-points and by scraping of the subgingival
      abutment surface. Differential phase-contrast microscopy showed a significant
      difference in plaque composition, especially when supragingival plaque was
      considered (P = 0.05). FEP coated abutments frequently harbored more coccoid
      microorganisms, whereas spirochetes or motile organisms were only detected around
      titanium abutments. Subgingivally, the number of colony forming units (CFU) in
      paper-points was comparable for both types of abutments. If the to-the-abutment
      adhering plaque was considered, the number of CFU was 5 times higher on the
      titanium abutments than on the FEP coated abutments. However, this difference did
      not reach a statistical level of significance (P = 0.38). The DNA probe analysis
      of the subgingival plaque collected with paper-points showed a slightly higher
      frequency and concentration of perio-pathogens around the titanium abutments.
      However, the inter-substratum differences were smaller than the inter-subject
      differences. The latter seemed to be related to patient's dental status.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8158514
TI  - Superficial cemental curettage: its efficacy in promoting improved cellular
      attachment on human root surfaces previously damaged by periodontitis.
AB  - This study was designed primarily to determine whether or not gingival
      fibroblasts attach to curetted cemental surfaces in periodontally-involved human
      teeth. Ten periodontally-involved human teeth were used. The superficial cementum
      from 5 teeth was removed by light mechanical curettage while no root treatment
      was performed on the remaining 5 teeth. Subsequently, the roots of all teeth were
      cut longitudinally to create 800 microns thick sections (slabs). Prepared slabs
      were then placed in 35 mm culture dishes, seeded with human gingival fibroblasts
      (HGF), and after 4 weeks processed for transmission electron microscopy (TEM).
      TEM results revealed flattened HGF on the noncuretted cemental surfaces that
      failed to attach. Fibrillar material was not seen between the HGF and cemental
      surfaces. In contrast, the HGF that grew on previously curetted cementum
      exhibited typical morphology of healthy, functional fibroblasts. Newly
      synthesized fibrillar material and collagen fibrils were noted, and both were
      apparently oriented towards the curetted cemental surface. Results strongly
      suggest that improved cellular attachment can be promoted on areas of root
      surface previously damaged by periodontitis if superficial cementum is first
      removed by mechanical curettage.

PMID- 8158515
TI  - Clinical evaluation of coralline calcium carbonate as a bone replacement graft
      material in human periodontal osseous defects.
AB  - A resorbable coralline calcium carbonate graft material (CalCarb) was compared to
      open flap debridement (DEBR) in human periodontal osseous defects. Following
      appropriate initial preparation procedures, flap surgery with defect and root
      debridement was performed in 20 patients. Alternating defects in each segment of
      surgery were treated with each procedure. Appropriate periodontal maintenance
      schedules were followed, and at 6 to 12 months a re-entry flap surgery was
      performed for documentation and finalization of treatment. Forty defects which
      received CalCarb grafts demonstrated significantly better mean defect fill of 2.3
      mm (67.7%) versus a mean defect fill of 0.7 mm (25.9%) (P < 0.01) for 39 defects
      treated with DEBR. Other hard tissue findings showed similar clinically superior
      results with the use of CalCarb. Relative defect fill results showed 88% positive
      (50% to 100% defect fill) responses with CalCarb and only 13% positive responses
      with DEBR. There were 7 times more failures (minimal response) with DEBR than
      with CalCarb. Soft tissue findings showed no significant differences between
      treatments. These results are similar to those with other synthetic and natural
      bone replacement graft materials. However, the ease of handling of the CalCarb
      material, its resorbability, and its potential for improved bone regeneration may
      be of clinical advantage.

PMID- 8158516
TI  - Oral sebaceous retention phenomenon.
AB  - An unusual lesion associated with obstruction of ectopic sebaceous glands of the
      retromolar mucosa is presented. Histologically, this was associated with mucus
      producing and respiratory metaplasia of the sebaceous ducts that also
      demonstrated microcyst formation. Sebaceous glands were hyperplastic. A review of
      the literature did not reveal a similar published example.

PMID- 8158517
TI  - Effects of febrile and epileptic convulsions on daily variations in plasma
      melatonin concentration in children.
AB  - Plasma melatonin was measured in 118 infants and children (39 controls, 28 with
      epileptic convulsions, and 51 with febrile convulsions). The control group
      displayed a typical circadian rhythm, with melatonin peaking between 0200 and
      0400. This normal daily variation significantly changed in the epileptic group,
      which showed a characteristic phase-advance, with the nocturnal melatonin peak
      appearing between 2400 and 0200. Febrile convulsions were associated with the
      disappearance of the normal circadian rhythm of melatonin, which was replaced by
      melatonin bursts throughout the light:dark cycle. In both febrile and epileptic
      children, melatonin levels were significantly increased in comparison with normal
      children.

PMID- 8158518
TI  - Pharmacological profile and diurnal rhythmicity of 2-[125I]-iodomelatonin binding
      sites in murine mammary tissue.
AB  - Recent studies demonstrated that melatonin treatment decreased the growth of
      mammary glands in pubertal and pregnant mice. In vitro, melatonin inhibited
      murine mammary gland growth at microM concentrations and increased it at pM
      concentrations. Melatonin-induced changes of cyclic nucleotide synthesis was also
      demonstrated in mammary gland slices in vitro. The objective of the present study
      was to assess the possible existence of specific binding sites for melatonin in
      murine mammary gland by using 2-[125I]-iodomelatonin as a probe. The specific
      binding of 2-[125I]-iodomelatonin to murine mammary gland membranes was rapid,
      saturable, and reversible, showed an affinity in the low nM range, and displayed
      time, temperature, and pH dependence. Scatchard analysis indicated the existence
      of a single class of binding sites that exhibited a diurnal rhythmicity in
      affinity (Kd) and receptor density (Bmax). A maximum in Bmax (267 +/- 42 fmol/mg
      protein) was found at the light period, while affinity was maximal during
      darkness (Kd = 1.33 +/- 0.22 nM). In competition studies dopamine and dopamine
      related agents, as well as 6-hydroxymelatonin and serotonin, but not melatonin,
      effectively displaced 2-[125I]-iodomelatonin from mammary binding sites. The
      results demonstrated a specific binding of 2-[125I]-iodomelatonin to murine
      mammary glands, with affinity in the low nM range, and a pharmacological profile
      that differed from that reported for 2-[125I]-iodomelatonin acceptor sites in
      other tissues.

PMID- 8158519
TI  - Effects of melatonin treatment on the gonadotropin-releasing hormone neuronal
      system and on gonadotropin secretion in male mink, Mustela vison, in the presence
      or absence of testosterone feedback.
AB  - The effects of subcutaneous melatonin capsules on the gonadotropin-releasing
      hormone (GnRH) immunoreactive (ir) system and the secretion of follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) have been tested in
      intact, castrated, and castrated adult male mink supplemented with testosterone.
      Animals were transferred in July, i.e., during the period of sexual rest, under a
      daily light:dark cycle of 16-hr light and 8-hr darkness and studied over 13
      weeks. GnRH (ir) perikarya, visualized by immunocytochemistry, were counted on
      serial coronal sections from the diagonal band of Broca to the infundibulum.
      Serum FSH and LH concentrations were measured by radioimmunoassay. In intact
      mink, melatonin induced a significant increase in the number of (ir) perikarya
      and in FSH and LH concentrations 3 and 8 weeks, respectively, after melatonin
      capsule implantation. In castrated mink, the number of perikarya and the
      concentrations of FSH, which had increased within 2 weeks after castration, did
      not change during melatonin treatment. In contrast, the concentration of LH,
      which were not altered by castration, increased 3-6 weeks after the onset of
      melatonin administration, suggesting a stimulation of GnRH release. In castrated
      testosterone-treated mink, the number of perikarya was increased as in castrated
      males, but the elevation of FSH in response to castration was prevented. Within 2
      weeks after melatonin capsule implantation, the concentrations of FSH decreased
      while those of LH remained low, indicating an inhibition of GnRH release. These
      results show that testosterone modulates the effect of melatonin on the activity
      of the GnRH-gonadotropin system.

PMID- 8158520
TI  - Effects of melatonin and the melatonin receptor agonist S-20098 on the vigilance
      states, EEG spectra, and cortical temperature in the rat.
AB  - The effects of melatonin (3 mg/kg i.p.) and the melatonin receptor agonist S
      20098 (3 mg/kg i.p.) on the vigilance states, electroencephalogram power spectra
      (0.25-25.0 Hz), and cortical temperature were determined in eight rats in the
      first 6-hr interval of the 12-hr light period. Compared to the vehicle injection
      both compounds reduced the power density in non-rapid eye movement sleep in the
      low frequency range (1-8 Hz) but did not affect the vigilance states and brain
      temperature. The present findings do not indicate that the stimulation of the
      melatonin receptor exerts a hypnotic effect at doses that had been shown to
      affect the circadian rest-activity rhythm.

PMID- 8158521
TI  - Melatonin rhythms in Arctic urban residents.
AB  - The 24-hr rhythm of salivary melatonin was measured in persons living in the city
      of Tromso (70 degrees N) at the following times of the year: in January at a day
      length of 2 hr of twilight, in June under continuous sunshine, and in March and
      September at about 12 hr light and 12 hr darkness. The hormone patterns varied
      widely between individuals, but, in general, they were consistent within most
      individuals between the seasons. Highest peak values occurred in January when the
      mean level was also significantly higher than at any other time of year. The
      lowest mean levels occurred in June. Although individual rhythms were not always
      apparent, the mean patterns showed significantly elevated melatonin
      concentrations during the night at all seasons. The June melatonin peak was
      similar to that in March and September, but appeared to be phase-delayed with
      increased melatonin concentrations from midnight until 0900. It is assumed that
      the delayed melatonin peak in June may be associated with a tendency among people
      to shift their activity/rest rhythm and that the pineal sensitivity to light is
      reduced in the morning in summer.

PMID- 8158522
TI  - Distribution of cholinergic and dopaminergic receptors in rainbow trout pineal
      gland.
AB  - The involvement of multiple receptors in modulating the function of the pineal
      gland was investigated by searching for dopaminergic and cholinergic receptors in
      trout pineal gland. Dopamine D1 and D2 receptors were measured using [3H]SCH23390
      and [3H]spiperone, respectively. Muscarinic and nicotinic cholinergic receptors
      were measured using quinuclidinyl benzilate ([3H]QNB) and [3H]methylcarbamyl
      choline, respectively. High-affinity choline uptake sites were measured using
      [3H]hemicholinium-3. The distribution of dopaminergic receptors varied throughout
      the pineal gland in that the density of D2 receptors, which was higher than that
      of D1 receptors, was most abundant in the distal region, exhibiting a value of
      112 +/- 17 fmol/mg tissue. The distribution of both muscarinic and nicotinic
      receptors was uniform throughout the pineal gland. However, the highest value for
      the high-affinity choline transporter (106 +/- 17 fmol/mg tissue) occurred in the
      proximal portion of the trout pineal gland. The results of these studies indicate
      that the pineal gland should not be viewed as a homogeneous tissue possessing
      identical density of various receptors. Furthermore, these results, along with
      previous data, are interpreted to suggest that different regions of pineal gland
      may indeed possess unique functions.

PMID- 8158523
TI  - Immunocytochemical localization of basic fibroblast growth factor in the rat
      pineal gland.
AB  - The immunocytochemical localization of basic fibroblast growth factor (b-FGF)
      during the postnatal development of the rat pineal gland was studied using a
      polyclonal antibody against the fraction 1-24 of bovine recombinant b-FGF. Basic
      FGF immunoreactivity was evident from day 20 after birth in the endothelial cells
      and perivascular spaces of the gland. Although b-FGF immunostaining showed its
      maximal expression at 30-45 days, it was maintained throughout the entire study
      period (up to 6 months), mainly in the distal zone of the gland. Pinealocytes did
      not show b-FGF immunoreactivity at any time. There were no differences in the
      localization patterns or the intensity of b-FGF immunostaining after the prenatal
      denervation with DSP-4, a neurotoxic amine. The physiological role of b-FGF in
      the adult pineal gland remains unknown; however, it does not seem to play a major
      role during the cytodifferentiation period of the parenchymal cells, or during
      the neovascularization in the early postnatal days. Furthermore, its
      immunocytochemical expression is not affected by the prenatal sympathetic
      denervation with DSP-4, in contrast with other neurotropic factors.

PMID- 8158524
TI  - The presence of nerve fibers immunoreactive for vasoactive intestinal peptide
      (VIP), peptide histidine isoleucine (PHI), and preproVIP(111-122) in the mouse
      pineal gland.
AB  - A low to moderate number of vasoactive intestinal peptide (VIP) and peptide
      histidine isoleucine (PHI)-immunoreactive nerve fibers with prominent boutons-en
      passage were demonstrated in the pineal gland of the mouse. The two peptides,
      which are parts of the same precursor molecule, were distributed identically in
      the gland. Positive fibers were present in the connective tissue septae in the
      gland, in the pineal capsule, and in the pineal parenchyma. No VIP-PHI
      immunoreactive elements were found in the deep pineal gland, in the pineal stalk,
      or in habenular and posterior commissures. This morphological distribution of
      immunoreactive nerve fibers, which is similar to the distribution in other
      mammals, indicates that the VIP/PHI fibers of the mouse pineal gland originate
      exclusively from perikarya in a peripheral ganglion, presumably one of the
      cholinergic ganglia of the head. No evidence for a VIPergic central innervation
      was found. VIP and PHI are connected via a bridging peptide equivalent to amino
      acids 111-122 of the precursor (preproVIP(111-122)). In order to demonstrate the
      possible existence of this peptide in intra-pineal nerve fibers, antisera
      directed against a synthetic sequence identical to preproVIP(111-122) and
      immunohistochemistry were applied. PreproVIP(111-122)-immunoreactive nerve fibers
      were observed in the mouse pineal gland, with the same distribution pattern and
      morphology as those immunoreactive for VIP and PHI. To quantify the peptide
      immunoreactivities, 50 mice pineals were pooled, extracted, and the
      concentrations were measured radioimmunologically. The concentrations of the VIP
      and preproVIP(111-122) immunoreactivities were 1.7 and 2.0 pmol/g, respectively,
      whereas the concentration of PHI was 0.9 pmol/g.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158525
TI  - Inhibition of rat acute inflammatory paw oedema by dihemiphthalate of
      glycyrrhetinic acid derivatives: comparison with glycyrrhetinic acid.
AB  - The anti-inflammatory profile of dihemiphthalate compounds of glycyrrhetinic acid
      derivatives in acute rat paw oedema induced by various vasoactive agents was
      compared with the parent compound. Three dihemiphthalate compounds (the di-sodium
      salt of 18 beta-olean-12-ene- 3 beta,30-diol di-O-hemiphthalate, 18 beta-olean
      9(11),12-dione-3 beta,30-diol di-O-hemiphthalate and olean-11,13(18)-diene-3
      beta,30-diol di-O-hemiphthalate), significantly inhibited development of
      carrageenan-induced rat paw oedema during the first 3 h (ED50 70, 90, and 108 mg
      kg-1 respectively, p.o.), while glycyrrhetinic acid (ED50, 200 mg kg-1) showed a
      significant inhibition of paw oedema 3 h after carrageenan treatment. The
      dihemiphthalate compounds also suppressed mouse paw oedema induced by histamine,
      bradykinin, and PAF acether at doses of less than 100 mg kg-1. However, these
      compounds failed to inhibit 5-HT-induced mouse paw oedema. Glycyrrhetinic acid
      had little effect on mouse paw inflammation induced by the above irritants. The
      three compounds at 10(-7)-10(-4) M, inhibited histamine-induced contraction of
      guinea-pig isolated ileum. However, concentration-response curves to 5-HT and
      bradykinin were not affected by the same compounds. These results suggest that
      the dihemiphthalate compounds modulate vascular permeability caused by endogenous
      vasoactive agents as one of the anti-inflammatory mechanisms. This action is
      quite different from that of glycyrrhetinic acid.

PMID- 8158526
TI  - Adenosine-echocardiography for the detection of coronary artery disease.
AB  - The use of adenosine-echocardiography to detect coronary artery disease was
      evaluated in 39 patients. Adenosine was infused intravenously at 0.14 mg/kg/min
      for 6 minutes with continuous recordings of two-dimensional echocardiography.
      Three minutes after the start of adenosine infusion, thallium (201Tl) was
      administered into a separate vein. Myocardial single photon emission computed
      tomography (SPECT) images were obtained 10 minutes and 3 hours after the 201Tl
      injection. Transient reduction of systolic wall motion after adenosine infusion
      was considered an abnormal ischemic response. Echocardiography detected a wall
      motion abnormality after adenosine infusion in 17 of 39 patients. 201Tl
      redistribution was observed in 28 patients. Agreements for the presence of
      myocardial ischemia or infarction between 201Tl SPECT and echocardiography were
      62% (24/39). The sensitivity of echocardiography in patients with single-vessel
      disease was 21%, but 76% with multi-vessel disease (p < 0.01 vs single-vessel
      disease). All side effects were tolerated well and disappeared within 1 or 2
      minutes after stopping adenosine infusion. Adenosine-echocardiography was
      particularly useful for the detection of multiple-vessel coronary disease.
      Simultaneous evaluation of wall motion and myocardial perfusion during adenosine
      induced maximal coronary vasodilation may improve the functional description of
      diseased myocardial segments.

PMID- 8158527
TI  - [Relation of T wave polarity in precordial V1 lead to right coronary pathoanatomy
      in inferoposterior wall acute myocardial infarction].
AB  - To test the hypothesis that right ventricular (RV) involvement may affect
      precordial T wave polarity, the relationship of T wave polarity in lead V1 to
      right coronary pathoanatomy was examined in 61 patients with first
      inferoposterior wall acute myocardial infarction (AMI) due to right coronary
      occlusion within 5 hours of symptom onset. One hundred healthy subjects served as
      normal controls. The patients were divided into two major groups based on the
      site of right coronary occlusion: group A (n = 34) with proximal occlusion and
      group B (n = 27) with distal occlusion. Each major group was classified into two
      subgroups according to the direction of the ST segment shift in lead V1. Group A
      was divided into subgroups A1 (27 patients with isoelectric or ST segment
      elevation) and A2 (7 patients with ST segment depression), and group B into
      subgroups B1 (8 patients with isoelectric or ST segment elevation) and B2 (19
      patients with ST segment depression). The incidence of upright T wave in lead V1
      (> or = 0.15 mV) was higher in the patients with proximal right coronary
      occlusion (70.6%) than in the controls (27%) (p < 0.001) or the patients with
      distal right coronary occlusion (18.5%) (p < 0.001). Upright T wave occurred most
      frequently in subgroup A1 (89%) (p < 0.001 vs controls), and least in subgroup B2
      (6%) (p < 0.05 vs controls). T wave polarity agreed with the direction of the ST
      segment shift in 40 of 61 AMI patients (66%) and disagreed in only one patient
      (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158528
TI  - [Changes in left ventricular inflow and pulmonary venous flow patterns during
      preload alteration in dilated heart].
AB  - Changes in left ventricular inflow (LVIF) and pulmonary venous flow (PVF)
      patterns during preload alteration were assessed in 30 patients with dilated
      heart, including 10 patients with dilated cardiomyopathy and 20 with old
      myocardial infarction. Transesophageal Doppler echocardiography was performed
      during lower body negative (LBNP, -40 mmHg) and positive pressure (LBPP, +40
      mmHg) in all 30 patients and 20 normal controls. Eight of the 30 patients showed
      the "pseudonormalization (PN)" pattern, and 22 showed the "decreased early
      diastolic wave (E) and compensatorily increased atrial contraction wave (A) (N
      PN)" pattern of LVIF in the control state. The diastolic wave (PVD) of the PVF
      and E of the LVIF were significantly higher, and the second systolic wave (PVS2)
      of the PVF and A of the LVIF were lower in the PN group than in the N-PN group.
      The amplitude of the atrial contraction wave (PVA) of the PVF in both groups of
      dilated heart patients was larger than in the normal group. The ratio of the
      amplitude of the atrial contraction wave to the total vertical deflection (A/H)
      of the apexcardiogram and mean pulmonary capillary wedge pressure (PCWP) in the
      PN group were greater than those in the N-PN group in the control state. LVIF in
      six of the 22 N-PN patients changed to the PN pattern during LBPP, and in three
      of eight PN patients changed to the N-PN pattern during LBNP. The six patients
      demonstrating the change from the N-PN to PN pattern showed a significant
      increase in PVD and PVA during LBPP compared with the control state, and a
      significant increase in PCWP in the control state compared with the 14 patients
      without a change in LVIF. Peak velocity of E in each group was decreased during
      LBNP and increased during LBPP, but peak velocity of A did not change during
      preload alteration. Peak velocity of PVS2 in the normal group was significantly
      decreased, and those of the PN and N-PN groups were decreased but not
      significantly during LBNP. The peak velocity of PVD was decreased during LBNP in
      the PN and N-PN groups, and the decrease was significantly higher in the former
      than in the latter.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8158529
TI  - [Fatty acid metabolic and perfusion abnormalities in hypertrophied myocardium
      assessed by dual tracer tomography using thallium-201 and iodine-123-beta
      methylpentadecanoic acid].
AB  - Fatty acid metabolic and perfusion abnormalities associated with cardiac
      hypertrophy were investigated using dual tracer tomography with thallium and a
      cardiac metabolic tracer, 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid
      (BMIPP), in eight patients with hypertrophic cardiomyopathy (HCM) and in three
      with hypertension (HT). Thallium and BMIPP uptakes were scored and analyzed in
      143 segments (13/heart) by comparison with the left ventricular wall thickness
      measured by two-dimensional echocardiography. Complete agreement of both scores
      in HT patients was significantly higher than that in HCM patients (64% vs 24%, p
      < 0.001), while a lower BMIPP uptake compared to that of thallium (mismatching)
      was observed more frequently in HCM than in HT patients (65% vs 31%, p < 0.001).
      The wall thickness significantly (p < 0.005) correlated with BMIPP uptake score.
      HCM patients showed a low BMIPP uptake in 22 hypertrophic segments (59%) and 15
      non-hypertrophic segments (41%), and reduced BMIPP uptake in 29% hypertrophic
      segments, while HT patients showed just five segments with decreased BMIPP uptake
      of which 4 were non-hypertrophic and only one hypertrophic. The left ventricular
      ejection fraction assessed by radionuclide ventriculography was normal and no
      regional wall motion abnormality was detected in any patient by echocardiographic
      and scintigraphic studies. Metabolic abnormalities detected by the iodine-123
      beta-methyl fatty acid analog in hypertrophic cardiomyopathy may be independent
      of thallium myocardial perfusion, regional wall motion, or the magnitude of
      cardiac hypertrophy, suggesting that fatty acid imaging may be useful in
      investigating the pathogenesis and subclinical abnormality of hypertrophic
      cardiomyopathy, and differentiation from secondary, induced cardiac hypertrophy.

PMID- 8158530
TI  - [Effect of verapamil on myocardial ischemia in patients with hypertrophic
      cardiomyopathy: evaluation by exercise thallium-201 SPECT].
AB  - The effect of verapamil on myocardial ischemia in patients with hypertrophic
      cardiomyopathy (HCM) was evaluated by exercise myocardial 201Tl SPECT (EX-Tl). EX
      Tl was performed before and after 8.1 +/- 6.1 weeks of oral administration of
      verapamil (240 mg/day) on 20 patients with HCM who showed transient 201Tl
      perfusion defects under control conditions. SPECT images were divided into nine
      segments. The 201Tl perfusion defect was visually scored and evaluated for four
      grades in each segment and the sum total grade was calculated as the defect
      score. Transient dilation index was calculated as a reflection of subendocardial
      ischemia. Improvements in defect score were demonstrated in 18 of 20 patients
      after administration of verapamil. The mean defect score decreased significantly
      from 5.1 +/- 2.3 to 2.5 +/- 2.4 (p < 0.001). Although 18 of 20 patients showed
      abnormal transient dilation index under control conditions, 16 showed improvement
      and 12 were normalized after verapamil therapy. Mean transient dilation index
      decreased from 1.24 +/- 0.19 to 1.08 +/- 0.10 (p < 0.01). Verapamil improves
      myocardial ischemia in patients with HCM.

PMID- 8158531
TI  - [Transcatheter closure of atrial septal defect with a prototype clamshell septal
      umbrella: one year follow-up].
AB  - Transcatheter closure of a secundum atrial septal defect was attempted using a
      prototype clamshell septal umbrella closure system in 11 patients (six males,
      five females, aged 4.4-15.0 years and weighing 16-51 kg). The balloon stretched
      atrial septal defects were 10.3 to 20 mm in diameter, and 23 to 40 mm diameter
      umbrellas were used. All patients improved clinically after the procedure. Fixed
      splitting of the second heart sound disappeared after closure in 10 patients,
      systolic murmur disappeared in nine, diastolic rumble in nine, and paradoxical
      ventricular septal motion in seven. Doppler color flow imaging immediately after
      implantation showed significant residual shunt in all patients; however, no shunt
      flow was observed in seven patients and minimal residual shunt was present in
      four one year after the procedure. Nine of 11 umbrellas demonstrated fracture of
      the stainless steel arm confirmed by chest radiography and cinefluorography. Arm
      fracture occurred between 1 week and 12 months after implantation. None of the
      devices were dislodged and no other complications were noted despite the
      fractures. Transcatheter closure of atrial septal defect is a feasible and useful
      procedure but the present device needs further modification.

PMID- 8158532
TI  - [Changes in hemodynamics and catecholamines during single-level exercise at the
      anaerobic threshold and 120% of the anaerobic threshold in normal subjects].
AB  - Exercise training usually involves the sustained performance of exercise at a
      prescribed intensity. The effects of exercise performed at the anaerobic
      threshold (AT) have been widely studied. The effects of single-level exercise on
      catecholamines and cardiac function were assessed at the AT, and at 120% of the
      AT in eight healthy Japanese men (mean age 21.9 +/- 1.8 years). 1) Symptom
      limited exercise testing utilized the ramp protocol with a bicycle ergometer (20
      watts/min) for measuring AT and peak oxygen uptake (peak VO2). 2) Exercise
      testing was repeated on another day, following the same protocol, with blood
      sampled to measure norepinephrine (NE) and epinephrine (E) in the resting control
      state and at the AT and peak exercise. 3) Single-level exercise testing at the AT
      and at 120% of AT utilized the bicycle ergometer on yet another day. Blood for
      measurement of NE and E was drawn at 3 and 7 min after achieving a steady-state
      condition. In addition, the cardiac index (CI) and stroke index (SI) were
      measured by the CO2 rebreathing method. (1) Mean AT and peak VO2 were 18.3 +/-
      1.3 and 40.2 +/- 3.0 ml/min/g, respectively. (2) NE and E measured during ramp
      exercise testing increased rapidly when the intensity of exercise exceeded the
      AT. NE measured after 3 and 7 min at the AT during single-level exercise equalled
      94.7% and 94.5% of the NE value measured at the AT of ramp exercise,
      respectively. NE measured after 3 and 7 min at 120% of the AT during single-level
      exercise was 124.7% and 144.7% at the AT of ramp exercise, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8158533
TI  - [Cardiac fibroma in an infant: comparison of echocardiographic findings with
      cardiac rhabdomyoma].
AB  - A 2-month-old boy presented with a cardiac tumor diagnosed by echocardiography
      and magnetic resonance imaging. An open biopsy specimen was diagnosed
      histologically as cardiac fibroma. The echocardiographic appearance of fibroma
      was compared with that of rhabdomyoma complicated by tuberous sclerosis. Fibroma
      is characterized by a partly high echo density area in the tumor suggesting
      calcification. Echocardiography is useful in the diagnosis of cardiac fibroma.

PMID- 8158534
TI  - [Diagnosis of ischemic heart disease by dipyridamole-stress two-dimensional
      echocardiography].
AB  - The diagnostic usefulness of dipyridamole-stress two-dimensional echocardiography
      was assessed in 82 patients consisting of 27 patients with angina pectoris, 42
      with myocardial infarction, and 13 control subjects. Two-dimensional
      echocardiographic monitoring was performed during dipyridamole infusion: 0.56
      mg/kg for 4 minutes, then discontinuation for 4 minutes, followed by a final
      infusion of 0.28 mg/kg for 2 minutes. The cumulative dose was 0.84 mg/kg.
      Worsening or fixed wall motion abnormality with unaffected baseline indicated a
      positive finding. All patients underwent coronary angiography. The sensitivity
      and specificity of dipyridamole-stress two-dimensional echocardiography for
      diagnosis of significant coronary artery stenosis (> or = 75%) were 84% (58/69)
      and 92% (12/13), respectively. The sensitivity of this method for the branches of
      the coronary artery was 85% for the left anterior descending artery, 80% for the
      right coronary artery, and 75% for the left circumflex artery. The sensitivity
      for single-, double-, triple-vessel disease was 75%, 81% and 100%, respectively.
      The sensitivity and specificity of the dipyridamole electrocardiogram (ST
      depression more than 0.1 mV) were 33% (23/69) and 77% (10/13), respectively. The
      appearance of dipyridamole-stress induced wall motion abnormality was
      significantly earlier than those of chest pain and ST segment depression. Side
      effects were observed in 43% (35/82) of patients, but were only mild and
      transient. Dipyridamole-stress two-dimensional echocardiography is the best
      method for detecting coronary artery stenosis and predicting the localization of
      lesion sites.

PMID- 8158535
TI  - IgG, IgM, and IgA response to HIV in infants born to HIV-1 infected mothers.
      Swiss Neonatal HIV Study Group.
AB  - Children born to HIV-1-positive mothers were prospectively tested for HIV
      reactive IgG, IgM, and IgA by Western blot, in order to study the children's
      humoral immune response in the background of passively transferred maternal IgG.
      In infected infants, a response was first seen at 1-3 months for env-reactive IgM
      and IgA, as well as gag-reactive IgM and IgG. This was followed by production of
      IgG to env, IgA to pol and to gag p17 and p55 at 7-9 months, and IgG to pol at 10
      12 months. IgG Western blot positivity by all interpretation guidelines in all
      infected infants was found by 10-12 months. Subsequently, only IgG to env and
      p24, and IgA to env were maintained in all, whereas IgG to pol and p17
      disappeared again in a significant fraction. A considerable proportion of
      uninfected infants also produced gag-reactive antibodies: IgM at 1-3 months,
      followed by IgG, which persisted in 10-20% and were also found in children born
      to uninfected mothers. These antibodies were, however, present at lower titers
      than in infected infants and were apparently produced in response to agent(s)
      different from HIV. Maternal antibodies to env disappeared significantly faster
      in infected than uninfected infants. Traces of HIV-reactive IgG were present for
      up to 21 months in children who subsequently seroreverted completely.

PMID- 8158536
TI  - Biphasic in vitro regulation of retroviral replication by CD8+ cells from
      nonhuman primates.
AB  - CD8+ T cells from naturally infected disease-resistant sooty mangabeys
      (Cercocebus atys) secrete a soluble factor which inhibits the in vitro
      replication of the simian immunodeficiency virus (SIV). To gain further insight
      on the mechanism(s) involved, CD8+ effector T cells and target cells from sooty
      mangabeys were immortalized and cloned. The target cells were then stably
      transfected with an SIV-LTR-CAT construct or with the parental CAT plasmid as a
      control. A quantitative RT-PCR method, providing the necessary sensitivity, was
      developed to monitor the influence of the cloned CD8+ T cells on the CATmRNA
      contained in the target cells. It could be demonstrated that a soluble factor was
      secreted by the cloned CD8+ T cells from sooty mangabeys, which appeared to
      regulate CATmRNA activity in a dose-dependent and reversible manner. Kinetic
      experiments showed that the CATmRNA transcriptional activity was initially
      augmented at 30 min postcoculture and was followed by a marked decrease in
      transcriptional activity after a few hours. This immediate early response could
      be mitigated utilizing H7, Calmodulin, or PDTC (a pyrrolidone derivative of
      dithiocarbamate), suggesting that the pathway was protein kinase-dependent and
      that the NF-kappa B site may be involved. The inhibitory effect could also be
      overcome using a protein synthesis inhibitor, suggesting that protein synthesis
      was needed to negatively regulate CATmRNA activity and hence SIV promoter
      activity.

PMID- 8158537
TI  - Lack of correlation between the number of circulating B cells and the
      concentration of serum antibodies reactive with the HIV-1 envelope glycoprotein.
AB  - Cells obtained from the peripheral blood of HIV-infected patients and volunteers
      immunized with HIV-1 vaccines are commonly used to study anti-viral responses,
      since lymphocytes from the central lymphoid organs are difficult to obtain.
      Analyses involving PBMC implicitly assume that circulating B cells provide an
      accurate reflection of the systemic humoral response induced by the HIV antigens.
      We examined this assumption by comparing the number of B cells secreting IgG anti
      gp160/120 antibodies in the peripheral circulation with serum antibody titers.
      Results indicate that neither the magnitude nor duration of the serologic
      response detected in HIV-infected patients or gp160/gp120-immunized volunteers
      reproducibly correlates with the number of B cells secreting anti-envelope
      antibodies in the blood.

PMID- 8158538
TI  - Intermittent therapy.

PMID- 8158539
TI  - Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary
      prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized,
      controlled clinical trial. LFPMI Study Group. Ligue Francaise de Prevention des
      Maladies Infectieuses.
AB  - The objective was to compare the efficacy and tolerance of monthly aerosolized
      pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first
      episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus
      (HIV)-infected patients. In an open, prospective, randomized multicentric
      clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or
      20% without a history of PCP or cerebral toxoplasmosis were randomized to receive
      for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily
      TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for
      gender) were homogeneous for age, risk group for HIV infection, initial CD4+
      lymphocyte count, and mean follow-up. The PCP rate per year of observation using
      an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with
      pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and
      biological side effects were observed in five patients on pentamidine and 33 on
      TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed
      during the study. The analysis showed no significant difference in time of
      development of toxoplasmosis, but only one patient was actually treated with TMP
      SMX. Survival was not significantly different in the two groups. Low-dose daily
      TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode
      of PCP in HIV-infected patients, but aerosolized pentamidine was better
      tolerated. However, TMP-SMX is less costly and should have a preventive effect
      for toxoplasmosis.

PMID- 8158540
TI  - Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma.
AB  - Neither single-agent therapy nor any combination treatment has been satisfactory
      enough to be regarded as standard in systemic advanced Kaposi sarcoma. In an
      attempt to achieve high efficacy in combination with low toxicity, we used a new
      liposomal formulation of doxorubicin. Pharmacologic data had established a long
      plasma half-life, an increased accumulation in tumor tissue, and a decrease in
      uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open
      label, dose-escalating trial 40 male AIDS patients with advanced Kaposi sarcoma
      were enrolled to receive intravenous "stealth" liposomal doxorubicin biweekly at
      doses of 10 mg/m2 (n = 10), 20 mg/m2 (n = 27), and 40 mg/m2 (n = 3). The median
      CD4 count at baseline was 25/microL. After six cycles (12 weeks), 39 patients
      were evaluable. Three patients (7.5%) showed a complete response, which was
      histologically confirmed. A partial response was documented in 33 patients (85%).
      Stable disease was observed in three patients (7.5%). During a median treatment
      duration of 25 weeks, four patients developed stomatitis (10%), and four patients
      (10%) experienced alopecia. The most frequent hematologic toxicity was
      neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 toxicity was seen
      in 30%. Toxicity was dose-dependent and more frequent in the 40 mg/m2 stratum.
      During a median observation period of 25 weeks, opportunistic infections occurred
      in 57.5% of the patient population. We conclude that liposomal doxorubicin at
      dose levels of 10 and 20 mg/m2 is safe and effective for treatment of advanced
      Kaposi sarcoma in AIDS. A controlled trial comparing liposomal doxorubicin to
      conventional combination therapy is underway.

PMID- 8158541
TI  - Injected-drug use: complications and costs in the care of hospitalized HIV
      infected patients.
AB  - The aim of this study was to determine the contribution of injected-drug-use
      complications to the utilization of inpatient care by persons infected with human
      immunodeficiency virus (HIV). Retrospective chart review was done of all hospital
      admissions between January 1, 1991, and December 31, 1991, with outpatient
      records reviewed to establish CD4 counts within 3 months of the date of
      admission. The participants included 284 consecutive admissions (189 patients);
      admissions were divided into two groups according to the Center for Disease
      Control 1993 expanded AIDS definition: those with AIDS (CD4 count, < 200
      cells/microliters) and those with early HIV disease (CD4 count, > 200
      cells/microliters). Thirty percent of admissions occurred among persons with
      early HIV disease. Among 189 individuals admitted to the hospital, 84% were male,
      62% were white, and 48% had injected drugs. Early HIV disease admissions were
      more likely to involve active injection-drug users (82% vs. 33%; p < 0.01).
      Admissions related to injected-drug use constituted 60% of early HIV disease
      hospitalizations, and this number rises to 72% if bacterial pneumonia is included
      as a substance abuse complication. Admissions related to injected-drug use
      constituted 27% of AIDS admissions; this number rises to 51% if bacterial
      pneumonia is included. Early HIV disease admissions were significantly shorter
      (9.9 vs. 12.6 days) and less expensive (mean charge, $9,592 vs. 12,873) than AIDS
      admissions but still accounted for 25% of inpatient HIV charges. Hospitalizations
      among HIV-infected persons early in the course of HIV disease are most often
      related to the medical complications of injected-drug use and account for a
      substantial expenditure of hospital resources.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158542
TI  - Recombinant human erythropoietin and health-related quality of life of AIDS
      patients with anemia.
AB  - To evaluate the effect of recombinant human erythropoietin on anemia and health
      related quality of life in patients with acquired immunodeficiency syndrome
      (AIDS), we initiated an observational study with an open-label multicenter
      treatment protocol that involved multiple academic and community physicians in
      the United States. Our subjects comprised 251 anemic (i.e., hematocrit < 30%)
      patients with a clinical diagnosis of AIDS using 1987 CDC criteria, age > or = 12
      years, and serum erythropoietin level < or = 500 IU/L. The initial dosage of
      recombinant human erythropoietin was 4,000 units subcutaneously for 6 days each
      week. Based on the patient's response to therapy, the dosage was increased
      sequentially to 8,000 units subcutaneously for 6 days per week. Our measurements
      included changes in mean hematocrit and health-related quality of life. The
      interview included measures of energy/fatigue; physical, social, role and
      cognitive function; depression; health perceptions; and life satisfaction.
      Adverse experiences were also documented to assess safety. Changes in mean
      hematocrit level from a baseline of 27.9% to 33.6% at week 12 (p < .0001) and
      34.5% at week 24 (p < .0001) were observed in patients treated with recombinant
      human erythropoietin. Adverse experiences, not clearly associated with AIDS, were
      reported by 10% of patients. Increases in energy (p < .05) were observed after 12
      and 24 weeks of drug therapy, and increases in health perceptions were seen after
      24 weeks (p < .05). No statistically significant increases or decreases were
      observed on measures of physical functioning, cognitive functioning, depression,
      social functioning, or home management activities over the 24-week follow-up.
      Anemia correctors (defined as hematocrit > or = 38%) showed greater improvement
      in energy, health perceptions, home management, and role function than
      noncorrectors. Study dropouts and those who died had significantly worse scores
      for health-related quality of life at baseline compared to study completers.
      Thus, the AIDS patients with anemia and serum erythropoietin levels < or = 500
      IU/L treated with recombinant human erythropoietin showed increased mean
      hematocrit and improved health perceptions and energy levels. The drug therapy
      was associated with increased feelings of energy, but it was not associated with
      other changes in health status and well-being in the AIDS patients completing the
      study. These observations need to be confirmed in randomized clinical trials.

PMID- 8158543
TI  - Spread of AIDS in rural America, 1982-1990.
AB  - Using a national county database, we examine the hypothesis of increasing spread
      of acquired immune deficiency syndrome (AIDS) in rural America. Data for county
      level AIDS caseloads for the period 1982-1990 were obtained by contacting state
      health officials of individual states. Yearly and cumulative AIDS cases by county
      or health district were converted to rates with use of the 1986 population
      figures. The data were grouped into 3-year periods, 1982-1984, 1985-1987, and
      1988-1990, and analyzed. The top 25 counties that had the highest rates of
      increase were identified, and their average population sizes were derived.
      Pearson's correlation coefficients between the rates of increase and county
      populations were also computed. The results corroborate data from previous
      studies based on selected regions and clearly point to an increasing spread in
      rural counties on a national basis. During 1982-1984, highly populated counties
      had the highest rates of increase in number of cases of AIDS, with the
      populations of the top 25 counties averaging 1.1 million. Between 1988 and 1990,
      the top 25 counties that had the highest rates of increase are mostly rural
      counties with an average population of 73,000. Not only are we presently faced
      with a much larger base of population infected with AIDS than before, the
      epidemic has also entered a dangerous phase of spreading to rural America where
      health care facilities are far less adequate than in urban areas.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8158544
TI  - Interpreting HIV seroprevalence data from a street-based outreach program.
AB  - A total of 4,375 subjects were recruited through continuous street outreach over
      31 months for interviews on HIV-related risk behavior and HIV-antibody testing.
      Changes over time among sampled subjects with respect to HIV infection and HIV
      risk behavior have been examined retrospectively, and significant and consistent
      trends noted across successive cohorts. Although overall 42% of the sample tested
      HIV antibody-positive, HIV infection exhibited a consistent downward trend from
      60% in the first quarter year of interviewing to 22% in the final quarter year.
      Scores on a multivariate index of HIV risk also declined significantly. Mean age,
      proportion of Black subjects, mean length of drug injection career, frequency of
      drug injection, and the use of shooting galleries all declined significantly
      across quarters as well. We argue that these observed differences result from a
      systematic sampling bias inherent in our outreach-driven sampling procedures,
      which initially favored recruitment of IDUs with greater behavioral and
      demographic risk for HIV.

PMID- 8158545
TI  - Understanding the dynamics of the HIV epidemic among Italian intravenous drug
      users: a cross-sectional versus a longitudinal approach.
AB  - We studied annual human immunodeficiency virus (HIV) seroprevalence and incidence
      in a large number of intravenous drug users attending drug treatment centers in
      three Italian urban areas. We also evaluated risk factors for HIV seropositivity
      and for HIV seroconversion. The results showed that HIV prevalence and incidence
      are declining. HIV prevalence declined dramatically in study participants that
      were < 25 years old. Prevalent HIV cases were associated with older age and
      longer duration of intravenous drug use; however, short duration of drug use
      increased the risk of seroconversion. The findings of our study suggest that
      comparing cross-sectional and longitudinal data contributes to a better
      understanding of the dynamics of the HIV epidemic among intravenous drug users.

PMID- 8158546
TI  - Predictors of unsafe needle practices: injection drug users in Denver.
AB  - To identify factors associated with unsafe needle hygiene, we studied 378
      injection drug users (IDUs) in Denver, Colorado. The sample was drawn from
      neighborhoods with large concentrations of injectors and crack smokers.
      Respondents were questioned about their needle hygiene practices during the 30
      day period prior to the interview. Unsafe needle hygiene, defined as injecting
      with previously used, nondisinfected needles, was reported by more than a third
      of those interviewed. Unsafe needle practices were associated with a number of
      factors, including heroin injection, perceived chance of getting AIDS, and lack
      of exposure to AIDS interventions in the community. The high percentage reporting
      unsafe needle practices within a 30-day interval points to the grave risk AIDS
      continues to pose for drug users. We conclude that the apparent success of
      exposure to AIDS intervention efforts in changing needle practices shows promise
      for prevention programs targeting drug injectors.

PMID- 8158547
TI  - The distribution of T-cell subsets among HTLV-I carriers in Japan.
AB  - Data on T-cell subsets from 89 human T-cell lymphotropic virus-I (HTLV-I)
      carriers and 25 seronegative people were analyzed to identify differences in T
      cell subset values among three subgroups: HTLV-I carriers with abnormal
      lymphocytes (Ably; n = 24), carriers without Ably (n = 65), and HTLV-I
      seronegatives (n = 25). Estimates of mean values were adjusted for age, sex,
      smoking, and alcohol drinking, as appropriate. The percentage of CD25+ T cells
      was elevated in carriers with Ably (mean, 16.7 +/- 1.0) compared with the
      seronegatives (11.4 +/- 1.4; p = 0.0002); individuals with CD25 T-cell
      percentages above the median for the seronegatives had a corresponding 5.4-fold
      risk for being a carrier with Ably. Similarly, the percentage of CD4 T cells was
      elevated in carriers with Ably. Conversely, the percentage of CD8 T cells was
      lower among both groups of HTLV-I carriers than in the seronegatives. There was a
      corresponding significant increase (p = 0.0004) of the CD4/CD8 ratio among
      carriers with Ably (1.57 +/- 0.12) compared with the seronegatives (1.22 +/-
      0.12). Among subjects with CD4/CD8 ratios above the median for the seronegatives,
      there were 6.8- and 4.5-fold risks for being carriers with or without Ably,
      respectively. The percentage of CD7 was lower among carriers with Ably (75.6 +/-
      1.6) than among seronegatives (78.9 +/- 1.5; p = 0.13). The percentage of beta
      interleukin-2-receptor-positive T cells did not vary among the three
      subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158548
TI  - Successful treatment of HIV-related thrombocytopenia with didanosine (ddI)

PMID- 8158549
TI  - Validity of three assays for HIV-1 antibodies in saliva.

PMID- 8158550
TI  - Effects of intravenous drug use and gender on the cost of hospitalization for
      patients with AIDS.

PMID- 8158551
TI  - Homosexual prostitution and the potential spread of HIV in The Netherlands.

PMID- 8158552
TI  - Orthotics: the state of the art.

PMID- 8158553
TI  - Distal thigh/arm index as a predictor of success for lumbar sympathectomy.
AB  - Data from 90 lumbar sympathectomies were reviewed to assess the role of a distal
      thigh/arm Doppler systolic index (DTAI) and of external magnetic flowmeter (MCBF)
      measurements for predicting patient outcome following lumbar sympathectomy. The
      presenting symptoms included impending gangrene, gangrene, rest pain, nonhealing
      ulcers, and disabling claudication. Of the 90 cases, clinical improvement
      occurred in 57% of the limbs. Major amputation was not required in 73% of the
      limbs. The MCBF data showed variability which masked the relationship to the
      effects of sympathectomy. DTAI test results were significantly related to
      outcome. For DTAI > 0.6 (57 patients), improvement occurred in 70% of the limbs,
      with major amputation not required in 86% of the limbs. For DTAI < 0.6 (33
      patients), improvement occurred in only 33% of the limbs, and major amputation
      was not required in 52% of the limbs. The Doppler systolic index has provided a
      noninvasive measure that can be used in conjunction with good clinical judgment
      for predicting the outcome of lumbar sympathectomy.

PMID- 8158554
TI  - Gait analysis in peripheral vascular insufficiency through-knee amputation.
AB  - Due to recent improvements in prosthetic limb componentry, through-the-knee (knee
      disarticulation) amputation has gained new interest for rehabilitation-minded
      amputation surgeons. Recent objective scientific studies from our gait analysis
      laboratory have described the walking characteristics of peripheral vascular
      insufficiency through-knee amputees, and have compared their function with
      similar patients amputated above (transfemoral), or below (trans-tibial), the
      knee joint. This paper provides a summary of that available information.

PMID- 8158555
TI  - A closed loop automated seating system.
AB  - This technical report presents the recent progress in the design and construction
      of a closed loop automated seating system. Preliminary test results are reported.
      The system is designed to measure seating surface forces and control the seating
      surface geometry of a seated human. It uses force information as feedback to
      determine custom seating contours which produce desired seating characteristics.
      Ultimately, the system is intended to be used for research studies with patients.
      The system consists of an electronically actuated, force-sensing seating surface
      which is controlled by a computer. Stepper motors are used to move force sensing
      probes up or down until the desired seating surface characteristic is attained.
      Preliminary test results are presented and analyzed. A force-equalizing control
      algorithm has been written and found to produce relatively uniform force
      distributions for soft, hemispherical loads of various weights.

PMID- 8158556
TI  - Comparison of functional and medical assessment in the classification of persons
      with spinal cord injury.
AB  - For many reasons, persons with spinal cord injury (SCI) are classified according
      to a set of guidelines in which the term classification refers to a numeric value
      based on some selection of motor, sensory, and/or functional tests. The resulting
      classification is used as a means of quantifying the extent of neurological
      injury. Scales that focus on neurological injury (in the acute phase) differ from
      those that focus on functional ability (in the chronic phase). The relationship
      among these scales in grouping persons with SCI has not been ascertained. The
      purpose of the present study was to compare several classification systems within
      the same group of spinal cord injured subjects. Thirty subjects with traumatic
      SCI were classified by the same examiner and grouped according to three
      classification systems: 1) the American Spinal Injury Association (ASIA) Scale;
      2) the Bracken Scale; and, 3) the wheelchair basketball (BB) Sports Test.
      Calculation of Spearman's Rho correlation coefficients showed positive
      associations between the ASIA Scale and BB Sports Test (0.81). The Bracken Scale
      showed a negative correlation with the ASIA system (-0.66) and the BB Sports Test
      (-0.48). Of the three classification systems, the ASIA Scale showed the greatest
      discrimination in grouping subjects with SCI in both mixed (complete and
      incomplete), as well as incomplete injuries. It was clear that these three
      systems could result in different patterns of subject grouping and thus might
      affect the outcome of the clinical research studies.

PMID- 8158557
TI  - Biomechanical analysis of body mass transfer during stair ascent and descent of
      healthy subjects.
AB  - The purposes of this study were to: 1) assess whole body center of mass (CM)
      motion in the frontal, sagittal, and transverse planes; 2) compare CM
      displacement with center of pressure (CP); and, 3) further define the stance and
      swing subphases of stair ascent (SA) and stair descent (SD) based on critical CM,
      CP, and ground reaction force (GRF) events. SA and SD were analyzed on a
      convenience sample of 11 subjects. Unpaced data were collected from 28 SA trials
      and 24 SD trials utilizing a bilateral SELSPOT II/TRACK data acquisition system
      and two Kistler force plates at a sampling frequency of 153 Hz. Twenty-six
      discrete data points were chosen from each trial for analysis. Each identified
      point detailed the intersection, separation, maximum or minimum value of CM, CP,
      or GRF in all three planes. Specific phases of SA and SD are presented and
      described. The actions of CM, CP, and GRF are presented during each phase.
      Results further refine the phases originally described by McFayden and Winter.
      Subtle differences in phases and duration of single and double support are
      demonstrated between SA and SD. Based on these results, it is apparent that SD is
      a more dynamic process with greater inherent instability. Knowledge of SA and SD
      phases and CM/CP dynamics in healthy, normal subjects will permit comparison with
      patients exhibiting various pathologies. Such comparison should facilitate the
      development of appropriate intervention strategies.

PMID- 8158558
TI  - The effect of handedness in tactile speech perception.
AB  - This study examined differential performance of normally hearing subjects using a
      tactile device on the dominant versus non-dominant hand. The study evaluated
      whether tactual sensitivity for non-speech stimuli was greater for the dominant
      hand as compared with the non-dominant hand, and secondly, whether there was an
      advantage for speech presented tactually to the dominant hand, resulting from a
      preferential pathway to the language processing area in the left cerebral
      hemisphere. Evaluations of threshold pulse width, dynamic ranges, paired
      electrode identification, and a closed-set tactual pattern discrimination test
      battery showed no difference in tactual sensitivity measures between the two
      hands. Speech perception was assessed with closed sets of vowels and consonants
      and with open-set Harvey Gardner (HG) words and Arthur Boothroyd (AB) words.
      Group mean scores were higher in each of the tactually aided conditions as
      compared with the unaided conditions for speech tests, with the exception of AB
      words in the tactile plus lip-reading plus audition/lip-reading plus audition
      condition on the right hand. Overall mean scores on the closed-set vowel test and
      on open-set HG and AB words were significantly higher for the tactually aided
      condition as compared with the unaided condition. Comparison of performance
      between the dominant and non-dominant hand showed a significant advantage for the
      dominant hand on the closed-set vowel test only. No significant differences
      between hands in either tactually aided or unaided conditions were evident for
      any of the other speech perception tests. Factors influencing this result could
      have been variations in degree of difficulty of the tests, the amount of training
      subjects received, or the training strategy employed. Although an advantage to
      presenting speech through the dominant hand may exist, it is unlikely to be great
      enough to outweigh possible restrictions on everyday use.

PMID- 8158559
TI  - Research device to preproduction prototype: a chronology.
AB  - This paper describes the evolution of the Wheelchair Aerobic Fitness Trainer
      (WAFT), a wheelchair ergometer developed for determination of aerobic capacity
      and the diagnosis of coronary artery disease in lower limb disabled persons whose
      mobility depends primarily on the manual wheelchair. The device was originally
      developed for use in research studies to determine peak exercise capacity in
      persons with spinal cord injuries and other lower limb disabilities and to
      formulate associated graded exercise stress test protocols. In subsequent
      research, the device was incorporated into a specially designed testing station
      for the detection of coronary artery disease in persons who cannot adequately
      undergo treadmill or cycle ergometry testing because of lower limb disabilities.
      Based on the usefulness of the device for both rehabilitation and diagnostic
      purposes, the WAFT has been brought into the technology transfer process of the
      Department of Veterans Affairs Rehabilitation Research and Development Service.
      Under a contract with Packer Engineering, Inc., Naperville, IL, development of a
      preproduction version of the device and six units for field evaluation has
      commenced. The preproduction prototype of the WAFT has incorporated numerous
      improvements over the original device and promises to expand the potential for
      future research, rehabilitation, and diagnostic applications.

PMID- 8158560
TI  - [A study of absolute and relative growth on rat skeletal muscle].
AB  - Standard development of plantaris muscle in Wistar rats in relation to growth (2
      86 weeks) was studied to define more reliable criteria of muscle hypertrophy and
      hyperplasia. The following variables were measured as indicators of respective
      factors; body weight and lower hind-limb length as physical factors, whole muscle
      weight and length as whole-muscle factors, and muscle fiber cross-sectional area,
      total fiber number and number of proliferating cell as intramuscular factors.
      When absolute growths were plotted against age, two stages were clearly observed
      for all factors. The transitional point for the two stage was observed at 10
      weeks of age (about 300g in body weight). The first stage was a "growing phase"
      and the second was a "steady phase". When the relative growth was considered in
      relation to body weight, most factors increased in logarithmic functions, while
      muscle weight and muscle fiber cross-sectional area showed a linear relation. It
      was suggested, therefore, factors concerned with muscle mass and transverse
      growth developed more with increase in body weight than age. Furthermore, the
      increase in total fiber number and the decrease in number of proliferating cell
      in the "growing phase" showed mirror images, suggesting that most proliferating
      cells detected in the muscles in the "growing phase" may be myoblasts. These
      results assure the validity of muscle weight/body weight ratio in the evaluation
      of muscle hypertrophy or atrophy. However, it is remember that animals over 10
      weeks of age (300g in body weight) should be used for correct evaluation of
      muscle hyperplasia for comparative or developmental studies of Wistar rats.

PMID- 8158561
TI  - The nurse's interaction with the AIDS patient.

PMID- 8158562
TI  - Update on oral hypoglycemics (continuing education credit).

PMID- 8158563
TI  - Suicide and the elderly: can the LP/VN help? (continuing education credit).

PMID- 8158564
TI  - A review of chronobiology and chronopharmacology (continuing education credit).

PMID- 8158565
TI  - The changing face of nursing students.

PMID- 8158566
TI  - Postanesthesia nursing care for ambulatory surgery patients post-spinal
      anesthesia.
AB  - There has been a renewed interest in spinal anesthesia in recent years. However,
      its use for ambulatory surgery patients has not been as well accepted as its use
      for inpatients because of the high incidence of postdural puncture headache
      (PDPH) and uncertain patient recovery time before hospital discharge. Recently,
      studies indicate that the incidence of PDPH can be lowered to an acceptable level
      by applying improved techniques such as the use of a 27-g spinal needle or a
      needle with a tip designed like a pencil point, such as a Whitacre (Becton
      Dickinson, Rutherford, NJ) or Sprotte (Pajunk, Geisingen, Germany) needle. Also,
      by using xylocaine or bupivacaine, which are short- or intermediate-acting local
      anesthetics, rather than tetracaine, a long-acting anesthetic, patients can be
      safely discharged from the hospital within 4 to 6 hours from the induction of
      anesthesia. These improved techniques have allowed spinal anesthesia to be a
      valid, even desirable, option for selected patients undergoing ambulatory
      surgery. When considering spinal anesthesia for ambulatory surgery patients, it
      is important that the postanesthesia care staff be knowledgeable, because nursing
      care is one of the three integral parts of total patient care that makes
      ambulatory surgery successful. The other two components are surgery and
      anesthesia management. This presentation reviews the history, indications,
      benefits, and complications of spinal anesthesia and recommends nursing care for
      patients undergoing ambulatory surgery.

PMID- 8158567
TI  - Extrapyramidal side effects of metoclopramide in outpatient surgery patients.
AB  - Metoclopramide frequently is used as an antiemetic for patients undergoing
      surgery. Although adverse reactions are rare, a potential exists for
      extrapyramidal side effects to occur. Nurses in both the preoperative and
      postoperative areas must recognize the symptoms and initiate appropriate
      treatment. Three case scenarios are presented that describe patients undergoing
      surgery in the outpatient setting who experienced extrapyramidal side effects
      after preoperative administration of intravenous metoclopramide. The scenarios
      illustrate the potential symptoms that may occur and their management.

PMID- 8158568
TI  - Practical points in the use of dopamine.
AB  - Dopamine and its mechanism of action, indications, dosage and administration, and
      precautions are reviewed. A central purpose of this article is to highlight the
      nursing implications for use of dopamine.

PMID- 8158569
TI  - Decision trees: helping the postanesthesia nurse to plan data analysis.
AB  - An important step in the research process is statistical analysis of the data.
      Data analysis should be planned as variables are identified, as level of
      measurement is determined, and as research questions or hypotheses are generated.
      The use of decision trees can assist the PACU nurse in determining which
      statistical tests are appropriate for the level of variable measurement in the
      study. The use of decision trees also can assist the PACU nurse when consulting
      with experts regarding appropriate statistical analysis.

PMID- 8158570
TI  - Cooperation: a management imperative?
AB  - In the fast-moving, ever-changing health care environment, quick resolution of
      conflicts will be the key to survival. This requires approaching those situations
      from a cooperative rather than confrontive mind-set and changes the skills
      necessary to be an effective negotiator.

PMID- 8158571
TI  - A model for rural health care.
AB  - Government health care reform initiatives are intended to assure that every
      American citizen has access to basic health care services and to decrease health
      care costs at the same time. Cuts in Medicare and Medicaid reimbursements and
      overall limits on health care services will require careful and efficient
      management by providers. This article is about how one rural hospital has
      survived when other small hospitals were forced to close and created an
      environment for success in the uncertain years ahead.

PMID- 8158573
TI  - Drop those four-letter words!

PMID- 8158572
TI  - Notes from the American Society of Anesthesiologists annual meeting.

PMID- 8158574
TI  - Rites of spring.

PMID- 8158575
TI  - Factors influencing pain management: a nursing perspective.
AB  - Pain management is an integral part of the daily practice of PACU nurses. Despite
      increased understanding of pain and advanced pain-management methods, the
      experience of moderate to severe pain continues for many patients. This article
      reviews factors that influence nurses' pain management. These factors include the
      difficulty involved with measuring pain and the characteristics and educational
      preparation of the nurse. Common misconceptions and corrections to these
      misconceptions are summarized, and implications for practice are given.
      Suggestions for continuing education, including resensitizing nurses to pain
      management, increasing nurses' knowledge base, and examining personal factors and
      inherent beliefs, are given.

PMID- 8158576
TI  - Behavioral responses and self-reported pain in postoperative patients.
AB  - Pain has been difficult to assess because of its multidimensional nature. The
      primary purpose of this study was to investigate the relationship between the
      nurse's assessment of behavioral cues to pain and self-reports of pain made by
      patients using patient controlled analgesia (PCA). This descriptive-correlational
      study used the PACU Behavioral Pain Rating Scale (BPRS), patient's self-report,
      and hospital's PCA pain-rating scale to investigate pain measurement. The
      convenience sample consisted of 36 postoperative, gynecological surgery patients.
      Pain assessments for this study were completed during the first 6 postoperative
      hours on patients who did not have complications. Five pain assessments were
      collected for each patient. Pain scores were highest during the immediate
      postoperative period and continued over 2 hours. Significant relationships (rs =
      0.56 to 0.80; P < 0.05) were found between the BPRS scores and the self-reports
      of pain. The relationship between the hospital's PCA pain rating scores and self
      reported pain was significant only during the second assessment (rs = 0.45; P <
      0.05). The BPRS consistently showed a moderate to high relationship with the
      patient's self-report of pain and had a stronger relationship with the patient's
      self-reported pain than with the hospital's pain scale.

PMID- 8158577
TI  - Developing an acute pain service in a multicultural setting.
AB  - Development of an Acute Pain Service in a multicultural environment can be a
      difficult and challenging endeavor. In addition to concerns about communicating
      with patients who speak a foreign language, the problem of integrating staff from
      many different backgrounds must be faced. Education for both patients and staff
      must be innovative, multifaceted, and individualized. At King Faisal Specialist
      Hospital and Research Centre in Riyadh, Saudi Arabia, the past 2 years have been
      a time of challenge and growth as an interdisciplinary team developed a pain
      service that meets the hospital's unique needs while fulfilling the goal of
      improved pain management for the patients.

PMID- 8158578
TI  - Induction of beta 2-adrenergic receptor mRNA and ligand binding in HeLa cells.
AB  - HeLa cells express low levels of beta-adrenergic receptor (beta AR) of the beta 2
      subtype. When exposed to sodium butyrate, receptor levels increased up to 4-fold
      in a time dependent manner, reaching a maximum after 12 to 15 h of treatment.
      Sodium butyrate treatment also caused a 3 to 4 fold increase in levels of beta
      2AR mRNA determined by hybridization blot analysis. The induction of beta 2AR
      mRNA temporally preceded the increase in receptor binding activity, reaching a
      maximum after 4 to 6 h of treatment, and remaining elevated for up to 24 h. Prior
      exposure of the cells to the protein synthesis inhibitor cycloheximide prevented
      the butyrate-induced increase in receptor binding but had no effect on the
      increase in receptor mRNA. Blocking DNA synthesis and cell growth by excess
      thymidine did not increase beta 2AR mRNA or binding or prevent the effects of
      sodium butyrate. Thus, butyrate appears to induce beta 2AR mRNA by a mechanism
      independent of DNA and protein synthesis.

PMID- 8158579
TI  - Labelling of D2-dopaminergic and 5-HT2-serotonergic binding sites in human
      trophoblastic cells using [3H]-spiperone.
AB  - We previously reported that dopamine (DA) inhibited the release of human
      placental lactogen (hPL) from human placental cells. We also demonstrated the
      presence of D2-dopamine receptors in membrane preparations of human term
      placenta. The aim of the present study was to characterize these D2 receptors on
      freshly isolated human trophoblastic cells. The binding of [3H]-spiperone to
      these cells showed a curvilinear Scatchard plot suggesting the presence of two
      classes of binding sites (Kd1 = 1.26nM; Kd2 = 44.3nM). Competition experiments
      showed the following inhibitory binding potencies: serotonin-2 (5-HT2) > or = D2
      >>> alpha-adrenergic, beta-adrenergic, D1-dopamine, thus suggesting the presence
      of 5-HT2 binding sites. We have examined this possibility by blocking [3H]
      spiperone binding to 5-HT2 receptors in the presence of 50nM ketanserin, a
      selective antagonist of 5-HT2 sites. Under this condition, the linear Scatchard
      plot obtained suggested a single population of homogeneous binding sites for [3H]
      spiperone with a Kd of 0.55nM. To further characterize placental D2 receptors we
      conducted binding experiments with [3H]-raclopride, an more selective D2
      antagonist. The linear Scatchard plot obtained with this ligand suggested one
      class of binding sites for [3H]-raclopride (Kd = 6nM) with the following
      inhibitory potencies: D2 >>> beta-adrenergic >> 5-HT2, D1, alpha-adrenergic.
      These results suggest an important paracrine function for DA in human placenta
      and show for the first time that [3H]-spiperone binds putative 5-HT2 receptors in
      human placenta.

PMID- 8158580
TI  - Characterization of the membranous antiestrogen binding protein: I. Partial
      purification of the protein in its active state.
AB  - We previously demonstrated that, in addition to the estrogen receptor, the
      Antiestrogen Binding Site (ABS) is also a potent mediator of the antitumorous
      activity of the clinical drug tamoxifen. Because of report discrepancies in the
      binding parameters of rat liver ABS we first attempted to improve binding study
      conditions. In this way buffer, protein concentration, methodology for bound/free
      ligand separation and phospholipidic ratio were determined. This work was used to
      evaluate the Stoke radius (4.4 S) and isoelectric point (pH = 6.6) of the protein
      in its native state. These studies constituted the obligatory transition from rat
      liver to pure ABS protein.

PMID- 8158581
TI  - Characterization of the membranous antiestrogen binding protein: II. Purification
      to homogeneity.
AB  - Our knowledge of the biological role of the antiestrogen binding site ABS in the
      antitumoral activity of tamoxifen, will be increased with the determination of
      its coding gene sequence. To this end our team has for some time attempted to
      purify this membranous protein. In this work we report the purification to
      homogeneity of ABS from rat liver in a six step succession. Specific
      photolabeling with a tritiated photoprobe, solubilization of rat liver
      microsomes, chromatofocusing of the labeled proteins, preparative electrophoresis
      on polyacrylamide gel, and two consecutive high performance liquid chromatography
      separations on C4 hydrophobic resin produced 2.5 micrograms of pure ABS by silver
      stain analysis of SDS-PAGE. The NH2-terminal residue of the protein appears to be
      blocked, which hinders the Edman degradation method for obtention of the whole
      protein sequence.

PMID- 8158582
TI  - Internalization of N-formyl peptide chemotactic receptor-ligand complex by human
      neutrophils. The role of the receptor's 2-kDa external domain and carbohydrates.
AB  - We treated human neutrophils with papain to remove the external 2-kDa domain and
      along with it the two oligosaccharide side chains of the N-formyl peptide
      chemotactic receptor and investigated what effect their absence has on the ligand
      receptor complex internalization. After prelabeling of the cells with 125I
      hexapeptide for 5 min at 22 degrees C, about 95% of the bound radioactivity was
      located on the cell surface. During the first 5-min incubation at 37 degrees C
      both the control and papain-treated cells internalized 73% of the receptor-ligand
      complexes suggesting that internalization is very rapid in human neutrophils and
      that removal of the external domain and the carbohydrates of the receptor does
      not affect the rate. However, the truncated receptor-ligand complexes were
      degraded at a faster rate because the radioactivity released into the medium was
      significantly higher and correspondingly the acid-resistant radioactivity
      significantly lower in the papain-treated neutrophils than in control cells
      already at 5 min and all subsequent time points. The radioactivity accumulated in
      the medium of the control and papain-treated neutrophils represented inactivated
      125I-hexapeptide as less than 5% of it at 5, 30 and 120 min were capable of
      rebinding. No receptor recycling was detected in either cells. These results
      indicate that removal of the 2-kDa external domain and the carbohydrates of the N
      formyl chemotactic receptors has little effect on the internalization rate of the
      receptor-ligand complexes but accelerates markedly their intracellular
      degradation.

PMID- 8158583
TI  - Expression and solubilization of a recombinant human neurokinin-1 receptor in
      insect cells.
AB  - The human neurokinin-1 receptor has been expressed in insect cells using a
      recombinant baculovirus. The expression level is about 10 times higher than that
      obtained in mammalian cells. The recombinant receptor was solubilized with CHAPS,
      and a PEG precipitation procedure was shown to be effective in regaining high
      affinity substance P binding. This system should allow large scale purification
      of the human neurokinin-1 receptor.

PMID- 8158584
TI  - Assessment of Helicobacter pylori infection.

PMID- 8158585
TI  - Evolving towards a more cohesive medical curriculum.

PMID- 8158586
TI  - Negative medicine.

PMID- 8158587
TI  - The genius of disease. 5. Drugs and art--Thomas De Quincey and Elizabeth Barrett
      Browning.

PMID- 8158588
TI  - Bleeding peptic ulcer: an audit of conservative management.
AB  - One hundred and twenty-six of 157 consecutive patients (80%) admitted for a
      bleeding peptic ulcer were treated conservatively and retrospectively analysed.
      There were 52% duodenal, 41% gastric and 7% combined ulcers. The initial shock
      index (pulse/systolic blood pressure) was in excess of one in 10%. For 22% of the
      patients no transfusion was required but 10% had more than 6 units of blood
      during their hospital stay. Forty-nine per cent were on nonsteroidal anti
      inflammatory drugs and 83% had at least one coexisting systemic disease. Six
      patients (5%) had a further haemorrhage, four of whom died. A total of 10
      patients (8%) died. Five of them were related to the peptic ulcer disease but
      also had terminal or multiple systemic diseases precluding any surgery. Their
      poor short-term prognosis shows how difficult it will be to effectively reduce
      the mortality in this particular group of conservatively treated patients, even
      with the recent advent of endoscopic haemostasis, and stresses the importance of
      carefully identifying high risk patients in trials mounted to improve on the
      current mortality figures.

PMID- 8158589
TI  - Management of tetanus: a review of 18 cases.
AB  - Eighteen patients with generalized tetanus seen during an 8-year period in three
      regional hospitals in Hong Kong are reviewed. Eighty-nine per cent of the
      patients were intravenous heroin addicts who developed a severe type of
      generalized tetanus with autonomic dysfunction. Pain or stiffness of the neck or
      back was the commonest presenting symptom, followed by trismus and dysphagia.
      Most of the patients developed muscle spasms within 24 h of the onset of
      presenting symptoms. Early ventilatory support and tracheostomy, together with
      intensive nursing care, were the mainstay of the treatment. Pulmonary and
      gastrointestinal complications were common during the course of illness and
      treatment of autonomic dysfunction was often unsatisfactory. The case fatality
      rate was 25% among the heroin addicts, but full recovery was the usual outcome
      for those who survived. The simultaneous administration of intrathecal tetanus
      immunoglobulin tends to reduce mortality.

PMID- 8158590
TI  - Collapse in an accident and emergency department.
AB  - Collapse is a common presenting complaint to accident and emergency (A & E)
      departments. This retrospective study of 4180 new attendances at a district
      general hospital A & E showed that this accounted for 2.9%. A wide disease
      spectrum was implicated. This patient group has a high admission rate (47.8%) and
      a high mortality rate (31.3%). The deaths occurred largely in the elderly and it
      is suggested that elderly patients should either be admitted for observation, or
      a careful screening carried out for underlying pathology. The diversity of
      disease precludes a standard management protocol.

PMID- 8158591
TI  - Informed consent: an evaluation of patients' understanding and opinion (with
      respect to the operation of transurethral resection of prostate).
AB  - The ability of patients to understand and recall information given prior to
      obtaining written consent was assessed in 55 patients who were due to undergo the
      operation of transurethral resection of prostate. The patients were also asked
      their opinion on informed consent. Most patients knew the position of the
      prostate and the purpose of the operation. Some aspects of the postoperative
      management and complications were less well remembered. In particular, 18% of the
      patients could not remember the possibility of retrograde ejaculation despite
      efforts to emphasize this. Of the patients who returned their questionnaires, 41%
      did not mind what happened to them provided they were made better; 54% trusted
      their doctor to do the right thing and did not think detailed explanation was
      important; 62% felt that consent forms are to protect the doctor's right; still
      most patients felt that consent forms were necessary. Sub-groups comparison
      showed no relationship between patients' attitude and their ability to recall
      information.

PMID- 8158592
TI  - Coroner's cases of death due to errors in prescribing or giving medicines or to
      adverse drug reactions: Birmingham 1986-1991.
AB  - The records for Coroner's Inquests in one district during a 6 year period were
      examined retrospectively to establish the number and nature of deaths which were
      due to errors in the prescription or administration of medicines, and those due
      to adverse drug reactions. The district has a population of 1.19 million (1991),
      and a total of 3277 inquests were opened during the period 1986-1991. Ten of the
      deaths were identified as due to errors of prescribing or giving drugs. During
      the same period, 36 deaths were caused by adverse drug reactions. These 46 deaths
      made up approximately one in 2000 of all deaths during the study period. About a
      fifth of deaths related to prescribing and administering drugs are due to errors
      and may be more easily preventable than deaths due to adverse reactions.

PMID- 8158594
TI  - Routine X-rays in nasal trauma: the influence of audit on clinical practice.
AB  - The introduction of treatment protocols require audited prospective data. The use
      of X-rays in patients with simple nasal trauma is common but of limited value. A
      prospective audit of this practice and the implications of introducing a 'no X
      ray' policy for these patients into the local casualty department are presented.
      Patients are spared radiation exposure and there are savings in patient
      throughput time and departmental costs. Casualty departments which have not
      already adopted such a policy are urged to do so. Where such a protocol is in
      use, audit to ensure adherence is encouraged.

PMID- 8158593
TI  - Informed consent: what do patients want to know?
AB  - Informed consent is an important aspect of surgery, yet there has been little
      inquiry as to what patients want to know before their operation. This study has
      questioned 50 patients within 3 months of an ENT (ear, nose and throat)
      operation. We found that most were happy to allow doctors to determine their
      treatment but they wanted to know about their condition, the treatment, and the
      important side effects. Fifty per cent of patients admitted worrying about some
      aspect of their recent surgery. More than two-thirds thought signing a consent
      form primarily signified agreement to undergo treatment and that it was a legal
      document; 54% thought there was an important medico-legal aspect. Over half
      thought information sheets would be reassuring, one-third thought they would
      provoke anxiety and 8% thought they would frighten them from having surgery.
      Closer examination of the answers to our questions showed that those who were
      most worried about aspects of their surgery had a higher mean anxiety score, as
      did those who thought an information sheet would be either frightening or anxiety
      provoking. However, a higher anxiety score was not associated with a desire to
      know less about the proposed treatment.

PMID- 8158595
TI  - Applied comparative anatomy of the avian middle ear.
AB  - The anatomy of the middle ear has been studied in nine species of birds, with
      particular reference to the structure of the ossicle and its relationship to the
      tympanic membrane. The morphology of the avian middle ear has been compared to
      that of the reconstructed human middle ear. Drum to stapes foot plate assemblies
      created during ossiculoplasty operations differ from the pattern found in the
      avian middle ear in a number of important respects and this may help to explain
      why they are often unsuccessful. It is not technically feasible to reproduce the
      avian middle ear pattern exactly in the human middle ear and developments in
      reconstructive technique should therefore be directed towards reproducing the
      three ossicle pattern of the mammalian ear.

PMID- 8158596
TI  - Impoverished Africa: any hope for the future?

PMID- 8158597
TI  - Art in hospitals: does it work? A survey of evaluation of arts projects in the
      NHS.

PMID- 8158598
TI  - Acrimony and the origin of St Peter's.

PMID- 8158599
TI  - Familial acanthosis nigricans.

PMID- 8158600
TI  - Excision of the inferior vena cava in the surgical management of retro-peritoneal
      sarcomas.

PMID- 8158601
TI  - Glutathione synthetase deficiency: a family report.
AB  - Glutathione synthetase deficiency is a rare inborn error of metabolism. Low
      levels of and at times unstable molecules of glutathione synthetase leads to
      glutathione deficiency affecting various systems of the body. The inheritance is
      thought to be of autosomal recessive variety. We diagnosed the condition in a
      neonate and proceeded to investigate the family. The results are discussed below.

PMID- 8158602
TI  - Rheumatism and the thyroid.

PMID- 8158603
TI  - Risks of manipulation.

PMID- 8158604
TI  - Reactions to food additives.

PMID- 8158605
TI  - Back pain.

PMID- 8158606
TI  - Premenstrual syndrome.

PMID- 8158607
TI  - The diagnosis and management of arteritis.

PMID- 8158608
TI  - All heal.

PMID- 8158609
TI  - Medico legal reports.

PMID- 8158610
TI  - Use of arsenicals.

PMID- 8158611
TI  - Adaptations of arboviruses to ticks.
AB  - Arboviruses differ from other viruses in their need to replicate in both
      vertebrate and invertebrate hosts. The invertebrate is a blood-sucking arthropod
      that is competent to transmit the virus between susceptible animals. Arboviruses
      transmitted by ticks must adapt to the peculiar physiological and behavioral
      characteristics of ticks, particularly with regard to blood feeding, bloodmeal
      digestion, and molting. Virus imbibed with the blood meal first infects cells of
      the midgut wall. During this phase the virus must contend with the heterophagic
      bloodmeal digestion of ticks (an intracellular process occurring within midgut
      cells) and overcome the as yet undefined "gut barrier" to infection. Genetic and
      molecular data for a number of tick-borne viruses indicate ways in which such
      viruses may have adapted to infecting ticks, but far more information is needed.
      After infection of midgut cells, tick-borne viruses pass to the salivary glands
      for transmission during the next blood-feeding episode. To do this, the virus
      must survive molting by establishing an infection in at least one cell type that
      does not undergo histolysis. Different tick-borne viruses have different
      strategies for surviving the molting period, targeting a variety of tick tissues.
      The infection can then persist for the life span of the tick with little evidence
      of any detrimental effects on the tick. Transmission to a vertebrate host during
      feeding most probably occurs via saliva that contains virus secreted from
      infected salivary gland cells. The virus then enters the skin site of feeding,
      which has been profoundly modified by the pharmacological effects of tick saliva.
      At least three tick-borne viruses exploit such tick-induced host changes. This
      phenomenon (saliva-activated transmission) is believed to underlie "nonviremic
      transmission," whereby a virus is transmitted from an infected to an uninfected
      cofeeding tick through a host that has an undetectable or very low viremia. Thus
      tick-borne viruses that have adapted to the feeding characteristics of their tick
      vectors may not need to induce a virulent infection (with high viremia) in their
      natural vertebrate hosts. Efficient transmission of tick-borne viruses between
      cofeeding ticks may be a means of amplifying virus infection prevalence in F1
      generations infected by transovarial transmission.

PMID- 8158612
TI  - Transposable elements as population drive mechanisms: specification of critical
      parameter values.
AB  - With a view to the possible use of transposable elements (TEs) as a mechanism to
      drive genes into insect vector populations, we used a three-parameter density
      dependent growth equation to examine the critical parameter values that determine
      whether or not a mobile element will spread and become fixed in a finite diploid
      vector population. Populations were simulated with parameter values affecting
      size, reproductive rate, density-dependence, and transposition efficiency of the
      mobile element. Simulations indicated that an equilibrium was reached quickly,
      typically in < 50 generations. Even when initially present at < or = 1% of a
      large population, the mobile element spread quickly and became fixed if
      transposition efficiency was equal to unity and infertility caused by the element
      decreased reproductive capacity by as much as 45%. These results were insensitive
      to the values of basic wild type reproductive rates and density dependence, but
      population size, transposition efficiency of the element, reproductive rate
      individuals bearing TEs and initial ratio of TE-bearing to wild individuals
      modified the outcome. As population size and transposition efficiency decreased
      in value, TEs became fixed less easily. However, even in populations as small as
      n = 100, an element with a transposition efficiency > 0.75 that reduces fertility
      < 25% will become fixed when introduced at a frequency as low as 1% of the total
      population. These results are consistent with previously reported population
      genetics models. They suggest that engineered transposons with a wide range of
      properties may be used to drive genes, such as those for parasite resistance,
      into wild vector populations.

PMID- 8158613
TI  - Seasonal occurrence and reproductive status of Opisocrostis bruneri
      (Siphonaptera: Ceratophyllidae), a flea on Franklin's ground squirrel,
      Spermophilus franklinii (Rodentia: Sciuridae) near Birds Hill Park, Manitoba.
AB  - Eight hundred and forty-nine and 1,503 Opisocrostis bruneri (Baker) were removed
      from Spermophilus franklinii (Sabine) in 1982 and 1983, respectively. Two
      discrete peaks in mean intensity of infestation were observed, one in early May
      and one in late August to early September. Overall prevalence of O. bruneri on S.
      franlinii was > or = 0.75. The observed biweekly prevalence on adult male and
      female squirrels was always > or = 0.73 and > or = 0.67, respectively. All
      juvenile squirrels were infested. Female fleas with undeveloped ovarioles, and
      with or without sperm in the spermatheca, were predominant during the first 6 wk
      that squirrels appeared above ground after hibernation. Parous females
      predominated thereafter. Peaks of nulliparous female fleas were observed in early
      May and early July. Female fleas were favored in each trapping period except
      during a 2-wk period from the beginning of May to the end of June. The mean
      biweekly sex ratio (male/female) of fleas removed from S. franklinii was 0.70 and
      0.72 in 1982 and 1983, respectively. Oogenesis in O. bruneri was not dependent
      upon the estrous cycle of female S. franklinii. It appeared that O. bruneri
      completed at least two generations per year in Manitoba.

PMID- 8158614
TI  - Larval diet, adult size, and susceptibility of Aedes aegypti (Diptera: Culicidae)
      to infection with Ross River virus.
AB  - The relationship of larval nutrition and adult body size to the susceptibility of
      Aedes aegypti (L.) to Ross River virus infection was examined. Large adult
      mosquitoes produced by feeding larvae a high-level diet consumed significantly
      more virus particles than did smaller mosquitoes. However, when a correction for
      body size was made, smaller mosquitoes were found to consume significantly more
      virus per unit of body weight. A host viremia of 2.4 log10 PFU/ml failed to
      infect mosquitoes of any size. Large Ae. aegypti mosquitoes were significantly
      more susceptible than small mosquitoes when fed on hosts with viremias of 4.8,
      5.7, 6.4, and 7.5 log10 PFU/ml, but differences in susceptibility were less
      apparent at higher viremias.

PMID- 8158615
TI  - Pathogenicity and limited transoothecal transmission of Steinernema carpocapsae
      (Nematoda: Steinernematidae) in adult female German cockroaches (Dictyoptera:
      Blattellidae).
AB  - Nongravid female German cockroaches, Blattella germanica (L.), and females with
      young or old oothecae were exposed to infective stage juvenile (L3) Steinernema
      carpocapsae (Weiser) All strain by topical application and continuous exposure.
      Topically applied nematodes resulted in < or = 40% mortality 7 d after
      inoculation, whereas 100% of females continuously exposed to nematodes were dead
      within 7 d. Females carrying old oothecae had significantly lower LT50s (0.07 h)
      than females with young oothecae (42.71 h) and females without oothecae (38.49
      h). Fully formed oothecae were not penetrated by the nematodes, even though
      infective juveniles were found in the vestibulum between the female genitalia and
      on the proximal end of the ootheca. Partially formed oothecae were infested
      (100%) by nematodes derived from the female. Topical application of nematodes to
      the proximal end, side, or keel of mature oothecae that were detached from
      females did not result in nematode infestation, and the nymphs emerged normally.
      Oothecae continuously exposed to nematodes were similarly not infested but
      exhibited significant mortality, probably caused by bacterial infection.

PMID- 8158616
TI  - Aponomma (Bothriocroton) glebopalma, n. subgen., n. sp., and Amblyomma glauerti
      n. sp. (Acari: Ixodida: Ixodidae), parasites of monitor lizards (Varanidae) in
      Australia.
AB  - Aponomma (Bothriocroton) glebopalma, n. subgen., n. sp., and Amblyomma glauerti,
      n. sp. (Acari: Ixodidae), are described from the monitor lizards Varanus
      glebopalma Mitchell and Varanus glauerti Mertens in Western Australia and the
      Northern Territory, Australia. The new subgenus is erected to accomodate A.
      (Bothriocroton) glebopalma, a new species with a deeply pitted and pilose scutum
      in both the adult and immature stages, unlike all other described species of
      Aponomma. This new species is found in an area where Aponomma fimbriatum Koch, a
      parasite of varanid lizards and various species of snakes, was the only known
      member of the genus found in both Western Australia and the Northern Territory.
      Amblyomma glauerti n. sp., an ornate Australian reptile tick found on the same
      two hosts in Western Australia and the Northern Territory, is also described.
      These two new species were recovered from formalin-preserved lizard specimens;
      therefore, nothing is known of their life cycles, except that all stages
      parasitize varanid lizards.

PMID- 8158617
TI  - Experimental transmission of Langat (tick-borne encephalitis virus complex) virus
      by the soft tick Ornithodoros sonrai (Acari: Argasidae).
AB  - Laboratory studies determined that the soft tick Ornithodoros sonrai Sautet &
      Witkowski is a competent vector of Langat (tick-borne encephalitis virus complex)
      virus. When ticks fed on suckling mice having a mean viremia of 10(7.2) plaque
      forming units per ml, 52% (n = 208) became infected, and 84% (n = 87) of the
      infected ticks transmitted virus by bite when fed individually on suckling mice >
      or = 27 d after the infectious blood meal. Overall, 79 of 184 (43%) of ticks
      exposed to the original viremic mice individually transmitted virus by bite when
      tested up to 351 d after the infectious blood meal. In addition, ticks
      transmitted virus both transstadially and transovarially. Some ticks that
      transmitted virus during their first transmission attempt were retested. These
      ticks transmitted virus during 81 (99%) of 82 refeeding attempts, including ticks
      that transmitted virus 512 d after the initial infectious meal. Therefore,
      Ornithodoros spp. should be considered as potential vectors of Langat and other
      tick-borne encephalitis viruses.

PMID- 8158618
TI  - Ixodes scapularis (Acari: Ixodidae) deer tick mesoscale populations in natural
      areas: effects of deer, area, and location.
AB  - Nymphal Ixodes scapularis Say deer ticks were collected at 22 parks or other
      natural areas on Long Island, New York, to examine the relationship between tick
      populations and geographic position, size of area, presence of white-tailed deer,
      Odocoileus virginianus (Zimmerman), and numbers of human Lyme disease cases in
      adjacent communities. Nymphal ticks were 93% less abundant when deer were absent
      and were also less common in smaller natural areas. Geographic position on Long
      Island was not important. Tick numbers were significantly correlated with human
      Lyme disease incidence in adjacent townships. A second survey of larval ticks
      from five areas where deer were absent and six where deer were present found
      larvae present at four of the five sites without deer, but at only 2% of the
      levels found where deer were present. These results suggest that populations of
      I. scapularis can occur and reproduce in the absence of white-tailed deer, so
      that eradication of all deer would greatly reduce, but not eliminate, all risk of
      Lyme disease.

PMID- 8158619
TI  - Tannins in treehole habitats and their effects on Aedes sierrensis (Diptera:
      Culicidae) production and parasitism by Lambornella clarki (Ciliophora:
      Tetrahymenidae).
AB  - Tannin concentration, measured as total phenolics, varied widely in natural
      treehole water throughout the period of development for Aedes sierrensis
      (Ludlow), the western treehole mosquito. Tannic acid induced a parasitic response
      in free-living populations of the protozoan Lambornella clarki Corliss & Coats,
      an effect not entirely explained by acidity. Tannic acid concentration influenced
      mosquito developmental rates, survival, size, and proportion females more than
      food level, L. clarki parasite exposure, or any interaction of treatments for Ae.
      sierrensis populations reared in artificial microcosms exposed to natural
      conditions.

PMID- 8158620
TI  - Development rate and mortality of immature Parasarcophaga (Liopygia) ruficornis
      (Diptera: Sarcophagidae) at constant laboratory temperatures.
AB  - Developmental time of Parasarcophaga ruficornis (F.) was determined at constant
      temperatures of 13, 16, 19, 22, 25, 28, 31, 34, and 37 degrees C. Estimates of
      the lower developmental threshold temperatures (tL) were 10.5, -7.0, 6.3, 8.8,
      and 7.7 degrees C and the thermal constants (K) were 65.15, 111.93, 152.13,
      229.66, and 388.22 degree-days (DD) for feeding larvae, wandering larvae, larvae
      (feeding + wandering), pupae, and total developmental time, respectively. Flies
      reached their maximum weight in pupal and adult stages at 25 and 28 degrees C,
      whereas minimal weights were recorded at 16 and 37 degrees C. The optimal
      temperature in terms of rapid development, low mortality, and greatest weight
      ranged between 22 and 28 degrees C.

PMID- 8158621
TI  - Laboratory and field trials of four repellents with Culex pipiens (Diptera:
      Culicidae).
AB  - During Operation "Desert Shield," 16 volunteers field-tested four insect
      repellents (deet, the lactone CIC-4, and the piperidine compounds AI3-37220 and
      AI3-35765) against biting mosquitoes at King Fahd Airport, Eastern Province,
      Saudi Arabia. CIC-4 and AI3-37220 (25% wt/vol) provided effective (> 90%)
      protection against bites for 4 h. Deet and AI3-35765 protected for only 2 h. The
      compounds subsequently were evaluated for repellency against laboratory-reared
      Culex pipiens L. CIC-4 was more effective than deet, AI3-37220, or AI3-35765 at
      the ED50 but not at the ED95 level in initial sensitivity tests using human
      volunteers. At the ED95 level, deet provided significantly better protection than
      either piperidine compound. In laboratory duration tests, AI3-37220 provided 8 h
      of effective (> 90%) protection against Cx. pipiens bites, deet and AI3-35765 7 h
      of protection, and CIC-4 2 h of protection.

PMID- 8158622
TI  - Effect of the red imported fire ant (Hymenoptera: Formicidae) and carcass type on
      the daily occurrence of postfeeding carrion-fly larvae (Diptera: Calliphoridae,
      Sarcophagidae).
AB  - Red imported fire ants, Solenopsis invicta Buren, caused an increased in the
      proportion of gaps in the daily occurrence of postfeeding larvae of Cochliomyia
      macellaria (F.) in carrion-baited traps. Chrysomya rufifacies appeared later in
      the decomposition process and over a wider period of days in goat than in rabbit
      carcasses. The dependence of presence or absence of a carrion arthropod taxon at
      a given point in succession on interactions between other arthropods or carcass
      type must be considered when using successional data to estimate postmortem
      intervals.

PMID- 8158623
TI  - Rearing Culicoides variipennis sonorensis (Diptera: Ceratopogonidae) on agar and
      nematodes.
AB  - Culicoides variipennis sonorensis Wirth & Jones was reared from egg to adult in
      petri dishes on a 0.5 or 1% agar substrate with bacterial-feeding nematodes
      (Pelodera, Panagrellus) as food. All larval stages except the first instar were
      observed attacking and feeding on nematodes. Developmental rate on agar was
      approximately 25% slower than that of larvae reared in pans of water with
      bacteria, fungi, and algae as food. Pupation success was approximately 75% from
      dishes (3.5 or 9 cm diameter) with 30 and 100 eggs, respectively. The technique
      has significant advantages for maintainance of small laboratory colonies and
      allows continuous observation of developing immatures for experimental studies.

PMID- 8158624
TI  - Ambient air temperature as a predictor of activity of adult Ixodes scapularis
      (Acari: Ixodidae).
AB  - Based on winter flagging experiments on Long Island, NY, adult Ixodes scapularis
      Say have an apparent threshold of questing activity at 4 degrees C. This
      threshold should be incorporated into public education efforts because the public
      may be at risk of contracting Lyme disease any time during the winter when
      temperatures exceed 4 degrees C.

PMID- 8158625
TI  - Stimulation of attachment in a camel tick, Hyalomma dromedarii (Acari: Ixodidae):
      the unintended result of sublethal exposure to permethrin-impregnated fabric.
AB  - The susceptibility of a camel tick, Hyalomma dromedarii (Koch), to permethrin
      impregnated military uniform fabric was studied to determine the effects of
      laundering and contact time. Separate contact toxicity tests were conducted with
      laboratory-colonized male and female ticks of uniform age. Unfed, unmated ticks
      were exposed for periods of 5, 10, 30, and 60 min to each of five fabrics:
      unwashed-untreated, unwashed-treated, and 1, 2, or 3 times washed after treatment
      (1-, 2-, 3-wash-treated). Treated fabric was impregnated with permethrin at 0.125
      mg (AI)/cm2. Laundering was by machine washing with detergent followed by hot air
      machine drying. Intoxication immediately after exposure was assessed by activity
      response: the proportion of ticks attaching to a host (rabbit) within 60 min and
      the average time elapsed between contact and insertion of mouthparts.
      Unexpectedly, permethrin exposure activated an attachment response in both sexes.
      At all contact times, and in each wash-treated group, a greater proportion of
      ticks attached, and did so more rapidly, than in controls. Mortality assessment
      24 h after exposure showed that females were more tolerant than males and
      experienced light mortality even after 60 min of contact. Both natural and
      acquired factors may account for permethrin tolerance in this species. Consistent
      with pyrethroid mode of action and pheromone function in ticks, it is
      hypothesized that sublethal levels of permethrin may act on H. dromedarii to
      induce premature or excess release of a neurosecretory substance that elicits
      attachment.

PMID- 8158626
TI  - Respiratory gas exchange in the tick Amblyomma hebraeum (Acari: Ixodidae).
AB  - Respiratory gas exchange was studied in unfed adult Amblyomma hebraeum Koch.
      Carbon dioxide emission was measured at 25 degrees C using flow-through
      respirometry to determine standard metabolic rate and the temporal pattern of
      gaseous emission. The standard CO2 production rate (sVCO2) of inactive ticks was
      0.0135 +/- 0.0085 ml g-1 h-1, and the standard O2 consumption rate (sVO2) was
      0.0158 +/- 0.0097 ml g-1 h-1. Ventilation was discontinuous and was characterized
      by periodic bursts of CO2 emissions at frequencies of 0.33 h-1-1.11 h-1. Low
      metabolic rate coupled with discontinuous ventilation may contribute to the
      ability of adult A. hebraeum to withstand prolonged periods of starvation and
      desiccation in the absence of a host.

PMID- 8158627
TI  - Control of larval Aedes aegypti (Diptera: Culicidae) by cyclopoid copepods in
      peridomestic breeding containers.
AB  - Mesocyclops longisetus (Thiebaud), Mesocyclops thermocyclopoides Harada,
      Mesocyclops venezolanus Dussart, and Macrocyclops albidus (Jurine) were tested
      for their effectiveness in controlling Aedes aegypti (L.) larvae in a variety of
      containers around homes in El Progreso, Honduras. All four cyclopoid species
      killed > 20 larvae per cyclopoid per d under container conditions. M. longisetus
      was most effective, not only because it was the most voracious predator, but also
      because it survived best in the containers. M. longisetus maintained long-term
      populations in 200-liter drums, tires, vases, and cement tanks (without drains),
      providing the cyclopoids were not dried or poured out. M. longisetus reduced
      third- and fourth-instar Ae. aegypti larvae by > 98% compared with control
      containers without cyclopoids. M. longisetus should be of practical value for
      community-based Ae. aegypti control if appropriate attention is directed to
      maintaining it in containers after introduction.

PMID- 8158628
TI  - Abundance and prevalence of Culicoides (Diptera: Ceratopogonidae) on some
      Philippine chicken farms.
AB  - In total, 10,067 biting midges of the genus Culicoides comprising 17 species were
      collected in a light trap survey of 50 chicken farms in the province of Batangas,
      southern Luzon, Philippines, between 14 September and 5 December 1988. The
      species of greatest prevalence and abundance were Culicoides effusus Delfinado,
      Culicoides peregrinus Kieffer, and Culicoides palpifer Sen & Das Gupta. Engorged
      females of C. effusus, C. peregrinus, C. palpifer, Culicoides oxystoma Kieffer,
      Culicoides arakawae (Arakawa), Culicoides guttifer (Meijere), Culicoides
      albibasis Wirth & Hubert, Culicoides huffi Causey, Culicoides clavipalpis
      Mukerji, and Culicoides wenzeli Delfinado were collected. The abundance and
      prevalence of C. effusus, C. peregrinus, and C. C. palpifer in the overall sample
      of farms as well as in farms with previous occurrence of leucocytozoonosis
      indicated that these species are potential vectors of Culicoides-borne
      Leucocytozoon caulleryi Mathis & Leger among chickens in this area. Although
      blood-engorged females of C. arakawae were collected frequently, the prevalence
      and abundance of this species were limited.

PMID- 8158629
TI  - Variability in circadian activity patterns within the Culex pipiens complex
      (Diptera: Culicidae).
AB  - Circadian activity was compared among four strains of Culex pipiens molestus
      Forskal from Iran, Egypt, two localities (Ebira and Yanagawa) in Nagasaki, Japan,
      and one strain of Cx. p. pallens Coquillett from Japan. Under a 16:8 (L:D) h
      photoperiod, all the strains showed peaks of activity at lights on and off, with
      additional activity during both light and dark periods; Egyptian females and both
      sexes of Cx. p. pallens were inactive during the photophase. Under 0:24 (L:D) h,
      the length of the free-running activity period was significantly shorter in the
      "Iran" (21 h) than in the other three Cx. p. molestus strains (range, 21-23 h)
      and Cx. p. pallens (approximately 24 h). Under 24:0 (L:D) h, the activity rhythm
      was obscured. The length of the period was shorter in 24:0 (L:D) h than in 0:24
      (L:D) h, violating Aschoff's circadian rule. Furthermore, the circadian peak did
      not always occur every day under 24:0 (L:D) h but rather exhibited "day
      skipping."

PMID- 8158630
TI  - Wildlife as hosts for ticks (Acari) in Antigua, West Indies.
AB  - A survey was conducted to determine the status of wild mammals and birds as hosts
      for Amblyomma variegatum (F.) and other tick species in Antigua. Surveys of wild
      mammals and birds were conducted periodically from September 1988 through May
      1991. Wild mammals surveyed included the small Indian mongoose (Herpestes
      auropunctatus Hodgson), Norway rat (Rattus norvegicus Berkenhout), and house
      mouse (Mus musculus L.), but only mongooses were surveyed intensively. Larvae and
      nymphs of A. variegatum, larvae of Boophilus microplus (Canestrini), and larvae
      of Ornithodoros puertoricensis (Fox) were recovered. The mean prevalences of
      infestation of mongooses by A. variegatum larvae and nymphs were 4.7 and 1.3%,
      respectively; maximums were 16.1 and 5.0%, respectively. The mean prevalence of
      infestation of mongooses by B. microplus was 3.2%. O. puertoricensis is reported
      from Antigua for the first time. The mean prevalence of infestation of mongooses
      by O. puertoricensis larvae was 41.2%, but seasonal prevalences ranged from 27.8
      to 55.0%. Of 610 birds representing 16 species, three Carib grackles (Quiscalus
      lugubris Swainson) were each infested with one larva of A. variegatum.

PMID- 8158631
TI  - Effects of anoxia during gamma irradiation on face fly fertility and viability
      (Diptera: Muscidae).
AB  - Irradiating 6-d-old Musca autumnalis De Geer pupae in nitrogen with 500-2,500
      rads did not affect adult emergence, female fecundity, or male competitiveness.
      Male and female fertility decreased with increased dose, reaching about 1% at
      2,500 rads. Egg to adult survival upon backcrossing irradiated males or females
      to unirradiated flies was only 7% at 1,500 rads and 0.7% at 2,000 rads. Doses of
      up to 2,000 rads did not affect male survival, but males treated with 2,500 rads
      had reduced survival rates. These results are better than those with irradiation
      in air and indicate that irradiation with 1,800-2,000 rads in nitrogen would
      maximize dominant lethality and minimize fitness loss.

PMID- 8158632
TI  - Seasonal and annual abundance of Amblyomma americanum (Acari: Ixodidae) in
      central Georgia.
AB  - Seasonal and annual changes in the abundance of Amblyomma americanum (L.) larvae,
      nymphs, and adults were monitored over a 5-yr period in the Piedmont
      physiographic region of Georgia. Tick abundance was monitored with cloth drags
      (all life stages) and CO2-baited cloth panels (nymphs and adults) monthly during
      March through September from 1987 through 1991. Larvae appeared in substantial
      numbers in July and were most numerous in August and September. Small numbers of
      unfed larvae apparently overwintered each year based on their presence during
      March, April, or May. Nymphs were most numerous from April through June and
      declined to much lower numbers by August and September. Adults were most numerous
      from March through May and virtually disappeared by August. These seasonal
      patterns were similar to those reported for A. americanum at other southeastern
      locations. Each life stage exhibited similar trends of annual abundance with an
      increase in 1988 followed by a relatively steady decline to levels equivalent to
      or below initial 1987 values by 1991. Major environmental variables that
      potentially could have influenced annual abundance were identified from Haile &
      Mount's (1987) computerized model of A. americanum population dynamics. Habitat
      type, host density, and day length were constants and rationally could be
      excluded as causes of annual variations in abundance; weather and host-finding
      rate were presumed to have been primarily responsible for these annual
      differences.

PMID- 8158633
TI  - Influence of annual and biennial prescribed burning during March on the abundance
      of Amblyomma americanum (Acari: Ixodidae) in central Georgia.
AB  - A 5-yr study to evaluate the influence of annual and biennial prescribed burning
      in March on the abundance of Amblyomma americanum (L.) was conducted on Oconee
      Wildlife Management Area in the Piedmont physiographic region of Georgia. Tick
      abundance on plots embedded in larger burned and unburned areas were monitored
      with cloth drags and CO2-baited cloth panels monthly during March through
      September from 1987 through 1991. Annual and biennial prescribed burning from
      1988 to 1991 significantly reduced the abundance of larvae, nymphs, and adults
      but did not alter their seasonal trends of abundance. Annual burning more
      consistently suppressed all life stages than biennial burning. The magnitude of
      tick suppression tended to increase with successive burns, especially with the
      annual burning regime. The order of vulnerability to direct incineration appeared
      to be overwintered larvae > adults > nymphs; however, only overwintered larvae
      were highly vulnerable. Consistent reductions in larvae during June-September
      following burning were associated with reduced litter depths and presumably
      lowered habitat suitability. During years of fire omission, the abundance of
      larvae on biennially burned plots increased to levels equal to or exceeding those
      on unburned plots. Based on cloth drag sampling, mean percentage control during
      1988-1991 for larvae, nymphs, and adults, respectively, was 80, 75, and 70% on
      annually burned plots and 48, 73, and 65% on biennially burned plots. Frequent
      late-winter prescribed burning, which is commonly used to achieve wildlife
      habitat management objectives, could be an effective and economical component of
      an integrated A. americanum control program in habitats ecologically suited to
      regimes of frequent fire.

PMID- 8158634
TI  - Siphonaptera of North America north of Mexico: Vermipsyllidae and
      Rhopalopsyllidae.
AB  - The six species of Chaetopsylla Kohaut, 1903, two species of Polygenis Jordan,
      1939, and one species of Rhopalopsyllus Baker, 1905 known to occur in North
      America north of Mexico are reviewed with respect to their host preferences and
      distribution. Keys are provided for the species, and their salient characters are
      illustrated.

PMID- 8158635
TI  - Natural food and feeding behavior of Culicoides furens larvae (Diptera:
      Ceratopogonidae).
AB  - The gut contents of Culicoides furens (Poey) larvae were compared with the
      relative abundance of potential food items in the natural larval habitat.
      Additional experiments examined the predatory behavior of the larvae by means of
      video recordings. Gut analyses indicated that filamentous green algae were the
      most frequently consumed food items. Diatoms, despite their high density in the
      soil, were not a major food source and many may have been ingested accidentally
      with algae. Gut content and video recording analyses indicated that nematodes,
      although occasionally eaten, probably were not the major dietary item. Moreover,
      fourth instars seemed to feed on nematodes more frequently during the day than
      during the night, possibly related to diel, small-scale vertical migrations of
      larvae in response to changes in light. When starved, larvae seemed to ingest
      nematodes more readily, as indicated by the absence of other items when nematodes
      were present in the gut. Overall, the results indicated that C. furens larvae are
      trophic generalists rather than solely predators.

PMID- 8158636
TI  - Analysis of the single-stranded DNA bacteriophage phi X174, refined at a
      resolution of 3.0 A.
AB  - The structure of the bacteriophage phi X174 was examined in a 2.7 A resolution
      map and refined, using 6.0 A to 3.0 A resolution data with F > or = 5 sigma (F).
      The final R-factor was 20.9% and the root-mean-square deviation from idealized
      bond lengths was 0.021 A. The Hendrickson-Konnert refinement was restrained by
      the phases derived from the molecular replacement icosahedral averaging
      procedure. The mature phage capsid consists of 60 copies of the F protein with
      426 amino acids, the G protein with 175 amino acids and the J protein with 37
      amino acids, as well as 12 copies of the H protein with 328 amino acids. The
      entire polypeptide chain of the F and G protein, all but the first N-terminal
      residue of the J protein, and 178 solvent molecules were included in the
      refinement calculations. The secondary structural features of the F, G and J
      proteins and their interactions with each other are described. The majority of
      the protein-protein interactions are between the icosahedral 5-fold related
      interfaces of the F and of the G proteins. These pentameric units of the F and G
      proteins form the 9S and 6S assembly intermediates, respectively. The J protein
      lacks any secondary structure and acts as a linking arm between the icosahedral 5
      fold related F proteins. Water molecules were introduced only after phase
      extension to 2.7 A resolution had been completed. The F protein is associated
      with lower "thermal" parameters and exhibits greater water order in its
      environment than the G and J proteins. The largest thermal parameters occur in
      residues on the viral surface. The solvent contributes to the interactions
      between the proteins. There is an interface of solvent molecules between the F
      and the G pentamers which stabilizes the pentameric G protein spikes in a crater
      centered at each of the icosahedral 5-fold vertices of the F protein capsid.
      Sequence alignments of the F, G and J amino acid sequences for the homologous
      bacteriophages G4, alpha 3, phi K and phi X174 with respect to the phi X174
      structure demonstrated the conservation of functionally important residues on the
      viral surface.

PMID- 8158637
TI  - The high-resolution structure of the histidine-containing phosphocarrier protein
      HPr from Escherichia coli determined by restrained molecular dynamics from
      nuclear magnetic resonance nuclear Overhauser effect data.
AB  - The solution structure of the histidine-containing phosphocarrier protein HPr
      from Escherichia coli has been determined by NMR in combination with distance
      geometry and restrained molecular dynamics. The structure is based on 1520
      experimental restraints identified from both three-dimensional 1H-1H-13C and 1H
      1H-15N nuclear Overhauser effect multiple-quantum coherence spectroscopy and two
      dimensional 1H-1H nuclear Overhauser effect spectra. Thirty-two four-dimensional
      coordinate frames were produced by metric matrix distance geometry, subjected to
      distance bounds driven dynamics, projected into three-dimensional space and again
      subjected to distance-bounds driven dynamics. These 32 distance geometry
      structures were refined further by restrained molecular dynamics (40 ps) in the
      GROMOS in vacuo force field. All 32 structures reached acceptable energy minima
      while satisfying the imposed restraints. Two of these structures were subjected
      to a further 200 ps of molecular dynamics simulation in water, using time
      dependent distance restraining, followed by a 200 ps free simulation without any
      distance restraining. The resulting structure is very similar to the X-ray
      structure of Bacillus subtilis HPr, but differs mainly in the position of the two
      loops containing the active site histidine residue 15 and residues 53 to 57
      relative to the rest of the structure. The unfavorable phi torsion angle that was
      found for residue 16 in the active center of unphosphorylated Streptococcus
      faecalis HPr was proposed to play a role in the activity of the protein. Although
      present at the early stages of the structure calculations, this torsion-angle
      strain disappeared in the final model obtained from molecular dynamics
      simulations in water using time-averaged distance restraining and upon releasing
      the distance restraints. This suggests that the strain may be an artifact of
      crystallization conditions instead of an essential element in the
      phosphorylation/dephosphorylation process.

PMID- 8158638
TI  - Stabilization of RNA structure by Mg ions. Specific and non-specific effects.
AB  - The stabilities of three different RNA fragments have been measured as a function
      of Mg2+ concentrations, and are interpreted in terms of two different models of
      Mg(2+)-RNA interaction. The models presume either tight binding of ions to
      specific site(s) in a folded RNA, or non-specific, electrostatic binding to both
      folded and unfolded forms; qualitatively different predictions are made for the
      melting temperature dependence on ion concentration. Three different modes of
      Mg2+ interactions with RNA structures are distinguished. Hairpins are stabilized
      by completely non-specific binding, with affinities the same as or weaker than
      those for single strand and duplex homopolymers binding Mg2+. In contrast, a
      ribosomal RNA tertiary structure is stabilized by specific binding of a single
      ion; since no other di- or trivalent ion is as effective as Mg2+, direct
      coordination of Mg2+ to the RNA structure is probably taking place. A third class
      of sites is best analyzed by the site-specific model, but any di- or trivalent
      ion is as effective as Mg2+; the ion(s) are probably localized in a region of
      unusually high charge density. The magnitude of a Mg(2+)-induced shift in RNAtm
      is itself not diagnostic of specific site binding or RNA tertiary structure,
      since large shifts can be observed for all three interaction modes.

PMID- 8158639
TI  - Molecular mechanisms of acid denaturation. The role of histidine residues in the
      partial unfolding of apomyoglobin.
AB  - Apomyoglobin adopts a partly folded intermediate conformation (I), sometimes
      referred to as a molten globule intermediate, near pH 4. To determine which
      histidine residues trigger this partial unfolding reaction, we made mutants in
      which nine of the twelve histidine residues in the protein are substituted
      individually. We then measured acid and urea-induced unfolding curves for these
      substituted proteins. Two acid unfolding transitions are observed: native (N) to
      intermediate (I), and I to unfolded (U). These data were fitted using a simple
      three-state model which has been shown to give an adequate description of acid
      and urea-induced unfolding of wild-type apomyoglobin. The aim is to quantify
      changes in the apparent standard Gibbs energy differences between N, I and U, as
      well as the unfolding mechanism, that result from these substitutions, and to
      test how well the model fits data for substituted proteins. In most cases, the
      model fits the data reasonably well, and significant changes in fitted unfolding
      parameters of various mutants are also clearly visible in the primary data. The
      following conclusions are drawn. (1) Histidines 24 and 119 synergistically
      stabilize native apomyoglobin (N) at pH 8, but together destabilize N as pH is
      decreased below seven. (2) Histidine 36 stabilizes N when it is protonated. (3)
      Histidine substitutions in the heme-binding pocket (residues 64, 93 and 97) have
      little effect on the stability of N, suggesting that the heme-binding pocket is
      open. (4) Histidine substitutions affect the N to I transition but have little
      effect on the I to U transition. (5) The simple model we use to describe the
      unfolding of apomyoglobin cannot account for all the data, particularly the
      effects of the H36Q mutation. The effect of protonated histidine 36 on
      stabilizing N is not included in the model. We suggest that breaking the hydrogen
      bond between histidines 24 and 119 by protonation when the pH is decreased from 6
      to 4 is an important part of triggering the partial unfolding of N to I, and
      likewise that formation of the hydrogen bond between histidines 24 and 119 may be
      a rate-determining step in the kinetic process of forming N from I during
      refolding.

PMID- 8158640
TI  - Structural origins of pH and ionic strength effects on protein stability. Acid
      denaturation of sperm whale apomyoglobin.
AB  - A recently developed approach to calculate the pH dependence of protein stability
      from three-dimensional structure information is applied to the analysis of acid
      denaturation of sperm whale apomyoglobin. The finite difference Poisson-Boltzmann
      method is used to calculate pKa values and these are used to obtain titration
      curves for the folded protein as well as for compact intermediates. The total
      electrostatic free energy change involved in apomyoglobin unfolding is then
      evaluated. Calculations are carried out of the unfolding free energy of the
      native (N) and the compact intermediate (I) of apomyoglobin relative to the
      unfolded state (U) over a range of pH at various ionic strengths. The
      contributions from key ionizable groups to the unfolding process are discussed.
      For the acid-induced partial unfolding of apomyoglobin near pH 5, the transition
      from N to I is found to be driven by three histidines that are exposed when the
      B, C, D and E helices unfold. Similarly, the unfolding of the compact
      intermediate I consisting of the A, G and H helices is driven primarily by a few
      carboxylic acids with low pKa values in the compact state. This picture is in
      contrast to the view which attributes acid denaturation to electrostatic
      repulsion resulting from the build up of positive charge. In fact, charge-charge
      interactions in myoglobin are found to be attractive at all pH values where the
      protein unfolds. pH-dependent changes in these interactions contribute to acid
      denaturation but other electrostatic effects, such as hydrogen bonding and
      solvation, are important as well. The effect of increasing ionic strength on
      unfolding is attributed to the decrease of attractive charge-charge interactions
      which destabilize the N state relative to I, but stabilize the I state relative
      to U by reducing the pKa shifts of a few critical carboxylic acids. The I state
      is found to be more stable than U at neutral pH thus accounting for its presence
      as an intermediate on the protein folding pathway. Our results have implications
      for the origins of compact intermediates or "molten globule" states.

PMID- 8158641
TI  - Adaptation to extreme environments: structure-function relationships in Emperor
      penguin haemoglobin.
AB  - The functional properties of the single haemoglobin (Hb) of Emperor penguin
      (Aptenodytes forsteri) have been investigated at different temperatures as a
      function of proton and organic phosphate concentration. The complete amino acid
      sequence has been established. Comparison with that of human HbA shows 12
      substitutions in the contact regions of alpha beta dimers. In addition to overall
      similarities shared with most of the avian Hbs previously described, this Hb
      shows significant differences, which could be related to the peculiar behaviour
      of this penguin. In particular we may consider that: (1) the shape of the Bohr
      effect curve seems well adapted for gas exchange during very prolonged dives,
      preserving penguin Hb from a sudden and not controlled stripping of oxygen; (2)
      the very minor enthalpy change observed at lower pH could be an example of
      molecular adaptation, through which oxygen delivery becomes essentially
      insensitive to exposure to the extremely low temperatures of the environment.
      Moreover, the small alkaline Bohr effect has been found to be only chloride
      linked, since the pH dependence of the oxygen affinity is totally abolished in
      the absence of this ion. These functional characteristics are discussed on the
      basis of the primary structure of alpha and beta-chains.

PMID- 8158642
TI  - Directed mutational analysis of bacteriochlorophyll a biosynthesis in Rhodobacter
      capsulatus.
AB  - Previous studies have established that most if not all of the genes required for
      synthesis of the Rhodobacter capsulatus essential photosystem are clustered on a
      46 kb region of the chromosome known as the photosynthesis gene cluster. This
      region has recently been sequenced in its entirety by Hearst and co-workers,
      revealing the existence of 23 open reading frames, many of which are thought to
      be involved in the synthesis of bacteriochlorophyll. In this study we have
      undertaken a systematic directed mutational analysis of 12 open reading frames in
      the photosynthesis gene cluster to evaluate whether individual open reading
      frames have a role in photopigment biosynthesis. The results of this analysis
      demonstrate that mutations constructed in seven open reading frames resulted in a
      loss of bacteriochlorophyll biosynthesis, concomitant with the accumulation of
      specific intermediates in the Mg-tetrapyrrole biosynthetic pathway. One mutation
      was observed to result in partial disruption of bacteriochlorophyll biosynthesis,
      leading to the accumulation of bacteriochlorophyll as well as an intermediate in
      the biosynthetic pathway. We also observed that disruptions constructed in four
      open reading frames had no discernible effect on the synthesis of photopigments.
      The results of this analysis are discussed with regard to our current
      understanding of the role of each of these open reading frames in the synthesis
      of the R. capsulatus photosystem.

PMID- 8158643
TI  - Analysis of mosquito vitellogenin cDNA. Similarity with vertebrate phosvitins and
      arthropod serum proteins.
AB  - The cDNA coding for vitellogenin of the mosquito Aedes aegypti was cloned and
      sequenced. An immunological analysis of expressed deletions from the 5'-end of
      the vitellogenin cDNA clones using vitellogenin subunit-specific antibodies
      showed that the small vitellogenin subunit is located at the N terminus and the
      large one at the carboxy-portion of the pre-provitellogenin. The position of the
      cleavage between the vitellogenin subunits in the pre-provitellogenin was
      identified by locating the N terminus of the large subunit. The cleavage site has
      a consensus RXRR for the subtilisin-processing endoprotease. Mosquito
      vitellogenin is highly hydrophilic with 17 putative N-linked glycosylation sites
      and 13 potential tyrosine sulfation sites. In contrast to known invertebrate
      vitellogenins, mosquito vitellogenin contains three polyserine domains that are
      similar to those of phosvitins in vertebrate vitellogenins. These polyserine
      domains, originally presumed to be vertebrate-specific, have several
      phosphorylation consensus sites in their sequences. Unlike other known
      vitellogenins, mosquito vitellogenin is rich in aromatic amino acid residues,
      tyrosine and phenylalanine, and in this respect is similar to insect serum
      proteins, arylphorins. This similarity suggests that mosquito vitellogenin may
      supply aromatic amino acids to the cuticle of rapidly developing embryos.

PMID- 8158644
TI  - X-ray diffraction study of the live squid retina.
AB  - In previous studies of invertebrate rhabdomes by X-ray diffraction,
      glutaraldehyde fixation of the retina was used because this tissue is very labile
      and, without fixation, disintegrates within an hour of dissection. However, with
      conventional X-ray apparatus more than ten hours exposure time was needed to
      record a diffraction pattern. In this study, X-ray diffraction patterns from
      unfixed squid retina could be successfully obtained by use of synchrotron
      radiation and a storage phosphor screen as detector. The diffraction spots were
      indexed on a two-dimensional hexagonal lattice of 60 nm. X-ray data was analysed
      by comparing Patterson functions calculated from the diffraction intensities with
      those based on model building. The hexagonal shape of microvillar cross section
      was suggested by the systematic weakness of (0, k) reflections beyond k = 4 and
      the appearance of the six symmetry-related diffuse maxima around (4 nm)-1. The
      best-fitting model showed a large gap between adjacent microvilli (approximately
      12 nm), which has been expected (for ionic current flow through the inter
      microvillus space to generate the membrane potential) but not observed with the
      chemically fixed retina, possibly due to an artifact of fixation. Also, the
      existence of massive inter-microvillus material, scarcely observed by
      conventional electron microscopy, has been confirmed.

PMID- 8158645
TI  - Characterization of two types of termination signal for bacteriophage T7 RNA
      polymerase.
AB  - The late bacteriophage T7 terminator (T7-T phi) encodes an RNA sequence that can
      form a stable stem-loop structure followed by a run of six uridylate residues;
      termination occurs at a 3' G residue just downstream of the U run. In this work,
      we have explored the features of this signal that are required for efficient
      termination by T7 RNA polymerase. Whereas replacement of the template-encoded 3'
      G residue with A, C, or U by site-directed mutagenesis had little effect, removal
      of the U-tract prevented termination. Deletion analysis indicates that the stem
      loop and U-tract are not sufficient for termination, and that sequences upstream
      from the terminator have marked effects on the position and efficiency of
      termination. A sequence within the human preproparathyroid hormone (PTH) gene
      that encodes an interrupted run of six U residues, but lacks an apparent stem
      loop structure, also serves as an efficient terminator for T7 RNA polymerase. We
      have mapped the primary site of termination in the PTH signal to a G residue that
      lies downstream of the U-rich run (UUUUCUUG). Deletion analysis indicates that
      the minimal region required for PTH terminator function extends only 23 bp
      upstream from the termination site, and subcloning of a 31 bp fragment that
      includes this region of the PTH signal provides efficient termination. A modified
      form of T7 RNA polymerase resulting from a single proteolytic cleavage between
      residues 178 and 179, or mutant polymerases that are altered in this region of
      the enzyme, fail to recognize the PTH signal while still terminating at T7-T phi.

PMID- 8158646
TI  - A novel site-specific recombinase encoded by the Streptococcus pyogenes plasmid
      pSM19035.
AB  - Genetic evidence suggests that the beta protein encoded by the Streptococcus
      pyogenes plasmid pSM19035 is involved both in the resolution of plasmid multimers
      into monomers and in DNA inversion. In this report we show that the highly
      purified beta protein is unable to mediate DNA recombination unless a host
      factor(s) is provided. In the presence of the host factor(s), the beta protein is
      able to catalyze in vitra intramolecular recombination between two specific sites
      on supercoiled templates: DNA resolution was obtained when the two recombination
      sites were directly oriented, whereas DNA inversion was the product if the
      recombination sites were in inverse orientation. In the absence of the host
      factor(s) the beta protein forms a specific complex with its target site. The
      beta protein binding site has been localized by DNase I footprinting to an 85 bp
      region that can be divided into two discrete sites (I and II). These sites are
      about 34 bp in length, they are separated by about 16 bp, and contain two 12 to
      13 bp imperfectly conserved sequences (half-sites) with dyad axis symmetry. The
      protein binds co-operatively to sites I and II; between 3.6 and 4.2 beta protein
      protomers are required to saturate the DNA substrate. These data, together with
      gel retardation assays, suggest that the protein binds to DNA as two dimers, one
      to each discrete site, and that the dimers probably interact with each other. The
      beta protein binding site, though it resembles that of other DNA resolvases of
      the Tn3/gamma delta (Tn1000) family, differs in that only two adjacent sites are
      found (sites I and II), while those DNA resolvases normally bind to three
      adjacent sites. The results presented here suggest that a host factor(s) could
      work as an accessory effector to compensate for the absence of the third binding
      site.

PMID- 8158647
TI  - A mutant hook-associated protein (HAP3) facilitates torsionally induced
      transformations of the flagellar filament of Escherichia coli.
AB  - Two mutants with defects in hook-associated protein 3 (HAP3) were isolated that
      exhibit impaired swimming only when they interact with a solid surface or a
      semisolid matrix. Motility and chemotaxis were normal in liquid media, even in
      media containing viscous agents, but cells failed to swarm in 0.28% agar. Mutants
      appeared to carry a full complement of flagella of normal configuration and
      length. However, filaments rotating counterclockwise close to a glass surface
      transformed from normal to straight, while filaments rotating clockwise
      transformed from curly to straight. Both transformations propagated from base to
      tip, as expected if torsionally induced. The mutations mapped to the middle of
      flgL, to structural gene for HAP3, and sequence analysis revealed the same coding
      change in both mutants: a substitution of cysteine for arginine 168. Our results
      show that the ability of a filament composed of normal flagellin subunits to
      resist mechanical stress depends on the structure of the protein (HAP3) to which
      it is attached at its base. The N-terminal sequence of HAP3 was found to be
      similar to the N-terminal sequence of flagellin, and the possibility that it
      provides a nucleation site for the C-terminal region of flagellin is discussed.

PMID- 8158648
TI  - pIV, a filamentous phage protein that mediates phage export across the bacterial
      cell envelope, forms a multimer.
AB  - Filamentous phage pIV is an outer membrane protein required for phage assembly
      and secretion. Chemical cross-linking and sedimentation experiments have been
      used to demonstrate that pIV from f1-infected Escherichia coli exists as a homo
      multimer, probably composed of 10 to 12 subunits. pIV secreted from spheroplasts
      remains soluble and does not form multimers. Synthesis of pIV from distantly
      related filamentous phages or from a bacterial homolog that participates in a
      specialized form of extra-cellular protein secretion in the same cell with pIVf1
      resulted in the formation of mixed multimers. This suggests that the homologous
      proteins themselves form homo-multimers. These structures could form gated
      channels that conduct assembling phage or specific substrate proteins across the
      outer membrane to the extracellular milieu.

PMID- 8158649
TI  - Three-dimensional structure of membrane-bound annexin V. A correlative electron
      microscopy-X-ray crystallography study.
AB  - We have used electron microscopy to analyse the structure of wild-type human
      annexin V (recombinant and placental) and of several mutants (single and double
      point mutants) bound to monolayers composed of DOPS, DOPE, or brain extract
      (Folch fraction III). On these phospholipids and on DOPS/DOPC (3:1, w/w) protein
      trimers, as also found in 3-D crystals, assemble to form a hexagonal lattice with
      a unit vector length of about 18 nm. The resolution obtained in projection is 1.7
      to 2.2 nm for wild-type and mutants. There are no significant differences between
      the annexin V mutants and the wild-type protein at this resolution. All proteins
      bind as trimers with their convex side harbouring the Ca(2+)-binding sites facing
      the membrane. A comparison of the 3-D reconstruction of annexin V wild-type with
      the high resolution crystal structure shows that the domain structure is
      preserved but the relative orientation of the modules (II/III) and (I/IV) is
      slightly changed so that the Ca(2+)-binding sites in all four domains (including
      the recently observed binding site in domain III) become coplanar to the
      membrane. The thickness of the molecule obtained in the 3-D reconstruction
      corresponds well with the thickness of the high resolution crystal structure
      indicative of peripheral binding of annexin V without substantial penetration of
      the membrane.

PMID- 8158650
TI  - Solution structure of GDP-tubulin double rings to 3 nm resolution and comparison
      with microtubules.
AB  - GDP liganded tubulin, which is inactive in microtubule assembly, polymerizes into
      rings more readily than the active GTP liganded protein. The structure of double
      rings made of highly purified GDP-tubulin has been characterized to 3 nm
      resolution with synchrotron X-ray solution scattering. The scattering profile has
      characteristic maxima due to closely packed double rings of 38 nm mean diameter,
      with a 5.5 nm mean spacing between the rings, and a 4.2 nm centre-to-centre
      spacing between non-globular tubulin monomers within both rings. There are
      probably 24 and 32 monomers in the inner and outer ring, respectively, and the
      double ring population is more than 75% homogeneous in size. Comparison of this
      double ring structure to the lattice of tubulin molecules in microtubules
      indicates that the tubulin rings are equivalent to pairs of protofilament
      segments curved tangentially to the microtubule surface, with bending angles of
      30 degrees and 22.5 degrees per tubulin alpha beta dimer. When the rings are
      modelled employing the same non-globular tubulin monomer as in microtubules, the
      best computer fitted scattering profiles correspond to monomer orientations
      equivalent to two microtubule protofilaments coiled sideways, with same or
      opposite polarity. Rings constitute the equilibrium assembly state of GDP
      tubulin, which is tensioned inside microtubules after GTP hydrolysis, causing
      their functional instability. In analogy with other nucleotide binding proteins,
      the inactive/active structural switch of tubulin is induced by the binding of the
      gamma phosphate and a coordinated Mg ion. It should involve domain rearrangements
      which cancel the bending of the tubulin dimer in the ring structure.

PMID- 8158651
TI  - Hydrodynamic analysis of tubulin dimer and double rings.

PMID- 8158652
TI  - The de novo design of an antibody combining site. Crystallographic analysis of
      the VL domain confirms the structural model.
AB  - In a protein design approach the molecular model of an artificial antibody Fv
      fragment was generated with predicted complementarity to part of the known
      crystal structure of chicken egg-white cystatin. The model of the Fv fragment was
      based on the three-dimensional structure of the anti-lysozyme antibody HyHEL-10,
      which was modified by substituting amino acid side-chains in the complementarity
      determining regions (CDRs) as well as the framework without altering the
      backbone. In the course of crystallization experiments with the bacterially
      produced Fv fragment crystals of the VL domain alone were obtained. These
      crystals diffracted X-rays to a resolution of 2.17 A and were shown to belong to
      the space group P2(1)2(1)2(1) with unit cell dimensions a = 46.89 A, b = 58.05 A,
      c = 83.22 A containing two VL monomers in the asymmetric unit. The crystal
      structure was solved by molecular replacement and refined to a crystallographic R
      factor of 17.5%. The two VL monomers exhibit an asymmetric mode of association,
      which is different from other crystallized VL domains described before and shows
      the peculiar feature of an isopropanol precipitant molecule buried at the
      interface. Both VL structures reveal a high level of similarity to the predicted
      three-dimensional model. With the exception of two loop segments in the framework
      region that are involved in crystal packing contacts, the backbone structures of
      the two VL monomers in the crystal and the molecular model of the VL domain are
      practically identical. Although six amino acid residues had been replaced in the
      hypervariable regions, the CDR conformations remained conserved and only minor
      deviations in the orientation of some side-chains and peptide planes were
      detected. The crystallographic analysis of the VL domain modelled as part of a
      complex between an artificial Fv fragment and the small protein cystatin,
      deliberately chosen as antigen target, confirms the concept of distinct
      structural classes for CDR backbones and supports our strategy for the de novo
      design of an antibody combining site.

PMID- 8158653
TI  - Salt effects on protein-DNA interactions. The lambda cI repressor and EcoRI
      endonuclease.
AB  - In this paper, finite-difference solutions to the nonlinear Poisson-Boltzmann
      (NLPB) equation are used to calculate the salt dependent contribution to the
      electrostatic DNA binding free energy for both the lambda cI repressor and the
      EcoRI endonuclease. For the protein-DNA systems studied, the NLPB method
      describes nonspecific univalent salt dependent effects on the binding free energy
      which are in excellent agreement with experimental results. In these systems, the
      contribution of the ion atmosphere to the binding free energy substantially
      destabilizes the protein-DNA complexes. The magnitude of this effect involves a
      macromolecular structure dependent redistribution of both cations and anions
      around the protein and the DNA which is dominated by long range electrostatic
      interactions. We find that the free energy associated with global ion
      redistribution upon binding is more important than changes associated with local
      protein-DNA interactions (ion-pairs) in determining salt effects. The NLPB model
      reveals how long range salt effects can play a significant role in the relative
      stability of protein-DNA complexes with different structures.

PMID- 8158654
TI  - Crystallization and preliminary X-ray analysis of the low molecular weight
      phosphotyrosyl protein phosphatase from bovine heart.
AB  - Two crystal forms of bovine heart phosphotyrosyl protein phosphatase (BHPTP) have
      been examined by X-ray analysis. One crystal form grows as long rods with
      triclinic crystal symmetry and diffracts to 3 A resolution. The diffraction
      pattern of this form of the crystal shows twinning about a major axis. A second
      crystal form of BHPTP grows as flat trapezoidal prisms with monoclinic symmetry
      C2, and unit cell parameters a = 95.3 A, b = 43.3 A, c = 41.2 A and beta = 113.5
      degrees. The unit cell dimensions indicate that there is one 18 kDa molecule per
      asymmetric unit. These crystals diffract to at least 2.2 A resolution and are
      resistant to decay in the X-ray beam.

PMID- 8158655
TI  - Crystallization and preliminary crystallographic study of beta-momorcharin.
AB  - Beta-Momorcharin from seeds of Momordica charantia, Cucurbitaceae Linn, has been
      crystallized using a vapor diffusion method. The crystals belong to space group
      P1 with unit cell parameters: a = 49.09 A, b = 50.58 A, c = 61.12 A, alpha =
      72.98 degrees, beta = 78.39 degrees, gamma = 76.97 degrees. There are two
      molecules in the unit cell and the diffraction data up to 2.4 A resolution were
      collected on an X-200B area detector, giving an Rmerge of 7.8%.

PMID- 8158656
TI  - Crystallization and preliminary X-ray diffraction studies of curculin. A new type
      of sweet protein having taste-modifying action.
AB  - A taste-modifying protein, curculin, has been crystallized by the vapor diffusion
      method using polyethylene glycol 400 as a precipitant. The crystals belong to
      orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions: a = 105 A, b =
      271 A, c = 48.7 A. The crystals diffract X-rays to at least a resolution of 3.0 A
      and are suitable for X-ray crystallographic studies.

PMID- 8158657
TI  - Furrowing surface contraction wave coincident with primary neural induction in
      amphibian embryos.
AB  - We predicted, and have now observed, a surface contraction wave in axolotl
      (Ambystoma mexicanum) embryos that appears to coincide temporally and spatially
      with primary neural induction and homoiogenetic induction, and with involution of
      the chordomesoderm. The wave starts from a focus anterior to the dorsal lip of
      the blastopore and spreads as an ellipse, until part of it encounters the rim of
      the blastopore and vanishes there. The remaining arc then continues over the
      dorsal hemisphere until it reforms an ellipse that decreases in size. About 9 to
      12 hours after it begins, the wave vanishes at a focus diametrically opposite its
      point of origin. The wave involves both local contraction and furrowing in the
      monolayer ectoderm. To a good approximation, the hemispherical portion of the
      ectoderm traversed by the wave becomes neuroepithelium, while the ectoderm not
      traversed by the wave becomes epidermis. The wave might provide a mechanism to
      determine the time and location at which neuroepithelial differentiation occurs.

PMID- 8158658
TI  - Magnesium cardioplegia prevents accumulation of cytosolic calcium in the ischemic
      myocardium.

PMID- 8158659
TI  - "Dose"-dependency and temporal characteristics of protection by ischaemic
      preconditioning against ischaemia-induced arrhythmias in rat hearts.
AB  - Brief episodes of ischaemia and reperfusion (preconditioning) can increase the
      resistance of the myocardium to ischaemic injury. We investigated the temporal
      characteristics of anti-arrhythmic protection by preconditioning. Rat hearts
      underwent regional ischaemia (+/- reperfusion) of the left coronary territory.
      Control isolated blood-perfused hearts underwent 40 min ischaemia; in the
      preconditioned groups this was preceded by one, two or three cycles of 5 min
      ischaemia and 5 min reperfusion. Control anaesthetized rats underwent 60 min
      ischaemia; this was preceded by three cycles of 3 min ischaemia and 3 min
      reperfusion in the preconditioned group. Preconditioning led to: (i) the
      abolition of ventricular fibrillation in both in vivo and in vitro preparations;
      (ii) a reduced incidence of ventricular tachycardia (from 100% to 8% in vitro and
      100% to 25% in vivo); and (iii) a reduced incidence of ventricular premature
      beats (from 246 +/- 36 to 8 +/- 5 in vitro and 85 +/- 21 to 24 +/- 13 in vivo).
      In isolated hearts protection was proportional to the number of preconditioning
      cycles. Although preconditioning caused a dramatic reduction in the severity of
      arrhythmias it did not result in any significant alteration in their temporal
      profiles. We conclude that protection by preconditioning against ischaemia
      induced arrhythmias is "dose"-dependent in rat hearts in vitro and results in an
      absolute reduction in the severity of ischaemia-induced arrhythmias rather than
      an alteration in their time-course, both in vivo and in vitro.

PMID- 8158660
TI  - Inhibition of sodium influx and improved preservation of rat hearts during
      hypothermic ischemia by furosemide and bumetanide: a 23Na- and 31P-NMR study.
AB  - The importance of the Na+/K+/Cl- co-transport system of the rat myocardial
      sarcolemma was studied under hypothermic ischemia by investigating the effect of
      the co-transport blockers furosemide and bumetanide on the sodium influx into the
      myocardium. The intracellular Na+ accumulation during hypothermic ischemia was
      followed by 23Na-NMR. For this purpose the shift reagent [Dy(TTHA)3-] (SR) was
      added to the Krebs-Henseleit (KH) perfusion solution. The same solution was also
      present during the hypothermic preservation. A significant reduction in the
      intracellular Na+ accumulation after 12 h was found when 100 microM furosemide
      was present during the perfusion and preservation periods. The intracellular Na+
      levels returned to the pre-ischemic values after 1 h of reperfusion with KH in
      both the treated and control groups. Dose-response studies have indicated that 1
      100 microM furosemide or 0.1 microM bumetanide added to the KH-SR solution
      reduced the Na+ influx significantly over 4 h of hypothermic ischemia. No
      statistically significant effect was found with furosemide concentration of 0.1
      microM or with bumetanide concentrations higher or lower than 0.1 microM. 31P-NMR
      measurements showed no effect of the 100 microM furosemide on the intracellular
      ATP, the sum of inorganic phosphate and phosphomonoester, or pH levels over 4 h
      or after 12 h of hypothermic ischemia. Hearts treated with KH containing 100
      microM furosemide showed, significantly higher functional recovery after 12 h of
      hypothermic ischemia than hearts treated only with KH. This study strongly
      indicates the existence of the Na+/K+/Cl- co-transport system in the intact rat
      heart sarcolemma, and its major role in sodium influx during hypothermic
      ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158661
TI  - Plasma and urinary heart-type cytoplasmic fatty acid-binding protein in coronary
      occlusion and reperfusion induced myocardial injury model.
AB  - The leakage of heart-type cytoplasmic fatty acid-binding protein (H-FABPc) from
      injured myocardial cells has been reported. We have previously proposed that its
      plasma and urinary levels could be used as an early indicator of myocardial
      injury and also reflect the severity of myocardial injury. To confirm this
      hypothesis, the time course of changes of the plasma and urinary H-FABPc was
      investigated during myocardial injury induced by coronary artery occlusion and
      reperfusion in dogs. The plasma elimination kinetics and urinary excretion
      kinetics of H-FABPc were also analysed in dogs which were given a bolus injection
      of exogenous H-FABPc. The distribution of circulating H-FABPc was determined in
      mice by whole-body autoradiography using 125I-labelled H-FABPc. In myocardial
      injury model, plasma and urinary H-FABPc level showed rapid increase after
      reperfusion. The elimination kinetic study revealed that H-FABPc was mono
      exponentially cleared from the circulation. The elimination rate constant (Ke)
      was 0.0275 +/- 0.0094/min (mean +/- S.D., n = 7) and the disappearance half-time
      (t1/2) was 27.5 +/- 8.4 min (mean +/- S.D., n = 7). Exogenous H-FABPc appeared in
      urine soon after administration, with the peak level being at 6.9 +/- 2.0 min
      (mean +/- S.D., n = 7). Whole-body autoradiography also demonstrated that 125I-H
      FABPc accumulated rapidly in the kidneys. This study demonstrated that H-FABPc
      leaked rapidly from injured myocardium and rapidly appeared in plasma and urine.
      Infarct size was closely correlated with the calculated H-FABPc release (r =
      0.89, r2 = 0.80, P < 0.01, n = 7) and with the amount of the urinary H-FABPc (r =
      0.94, r2 = 0.88, P < 0.01, n = 7). These data suggest that measurement of the H
      FABPc levels in plasma and urine might be useful for the early detection of
      myocardial injury and also for the assessment of infarct size.

PMID- 8158662
TI  - Phorbol ester-induced ventricular fibrillation in the Langendorff-perfused rabbit
      heart: antagonism by staurosporine and glibenclamide.
AB  - Using a paced Lagendorff-perfused rabbit heart paradigm, we investigated the role
      of protein kinase C (PKC) in the development of ventricular fibrillation (VF) in
      hearts subjected to hypoxia (12 min) and re-oxygenation (40 min). We studied the
      effect of putative activators and inhibitors of PKC on the incidence of VF.
      Hearts exposed to 4 beta-phorbol,12,13-dibutyrate (PDBu), isophorbol or the
      membrane permeant diacylglycerol analog, 1-oleoyl-2-acetyl-rac-glycerol (OAG),
      during the prehypoxic phase had an increased incidence of VF during the hypoxic
      and reoxygenation periods. The incidence of VF was 90%, 83% and 75% in hearts
      exposed to PDBu, isophorbol and OAG, respectively (P < 0.05 vs control).
      Perfusion of hearts with PDBu was associated with a significant increase in the
      membrane fraction of cardiac PKC activity. In the presence of the inactive
      phorbol ester 4 alpha-phorbol didecanoate, the incidence of VF was 17% (P > 0.05
      vs control). PKC activators were profibrillatory at concentrations that did not
      affect cardiac function: neither left ventricular developed pressure nor coronary
      perfusion pressure were affected. The effect of PDBu was antagonized by
      staurosporine: the incidence of VF was 17% in PDBu+staurosporine treated hearts
      (P < 0.05 vs control). To further study the profibrillatory effect of PDBu,
      hearts were exposed to PDBu in the presence of the ATP-dependent potassium
      channel antagonist glibenclamide. The latter prevented PDBu-induced VF. The
      results show that under the conditions employed, PDBu-induced activation of PKC
      induces redistribution of PKC activity and is associated with the development of
      VF.

PMID- 8158663
TI  - Fluidity of chicken ventricular plasma membranes during development in-ovo and
      after birth: spin labelling and fluorescence studies.
AB  - The fluidity of isolated chicken ventricular plasma membranes was investigated by
      ESR spectroscopy, using three doxylstearic spin labels (5-SASL, 10-SASL and 16
      SASL), and by fluorescence anisotropy measurements, using DPH probe. The analysis
      of 2T1 splitting constant and rotational correlation frequency have shown
      differences, during in-ovo development, characterized by a rigidification phase
      with a maximum at 19 days of development, just before hatching, followed by a
      fluidification phase after birth. These phenomena were also improved by DPH
      fluorescence and dynamical analysis of the hydrophobic 16-SASL probe.

PMID- 8158664
TI  - R56865, a Na(+)- and Ca(2+)-overload inhibitor, reduces myocardial ischemia
      reperfusion injury in blood-perfused rabbit hearts.
AB  - The cardioprotective effects of R56865 were studied in isolated rabbit hearts,
      blood-perfused with a support rabbit system. The effect on ischemic injury was
      evaluated by comparing myocardial contracture and contents of ATP catabolites and
      of lactate during 60 min of normothermic ischemia in untreated hearts (group I)
      and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia
      (group II; n = 5 in each group). R56865 delayed the onset, and decreased the
      extent of ischemic contracture, but had no effect on the myocardial content of
      ATP, of its catabolites of lactate. The effect on reperfusion injury was studied
      by monitoring left ventricular function during 80-min reperfusion after the 60
      min ischemia in three groups (n = 6 in each): an untreated group (group I) and
      two groups treated with R56865 given either before (group II) or after ischemia
      (group III). Ultrastructural changes and cellular calcium distribution after
      reperfusion were also studied. R56865 improved the recovery of function and
      prevented contracture during reperfusion. Left ventricular end-diastolic pressure
      was 13.2 +/- 2.8 mmHg in group II and 31.3 +/- 8.1 mmHg in group III vs 45.0 +/-
      2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left
      ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0
      +/- 5.4%, 98.9 +/- 6.1%, 85.3 +/- 4.8% of baseline values, respectively, in group
      II, to 64.5 +/- 3.0% (P > 0.05), 76.8 +/- 3.0%, 70.2 +/- 4.0% in group III, vs
      52.0 +/- 6.5%, 58.9 +/- 6.9% and 53.6 +/- 5.8% in untreated hearts (P < 0.05 for
      II or III vs I). Coronary flow was 24.5 +/- 2.2 ml/min and 19.8 +/- 1.8 ml/min in
      groups II and III vs 14.8 +/- 0.7 ml/min (P < 0.05) in the untreated group. On
      histology the myocardium in hearts treated either before or after ischemia was
      well protected and calcium distribution was almost normal after reperfusion,
      while in untreated hearts, most of the myocardium displayed irreversible damage
      accompanied by massive intracellular calcium accumulation. We conclude that
      R56865 could attenuate Ca(2+)-overload, thereby reducing myocardial ischemia
      reperfusion injury after an extended period of ischemia.

PMID- 8158665
TI  - The protective effect of heat stress against reperfusion arrhythmias in the rat.
AB  - Heat stress provides protection against mechanical dysfunction and myocardial
      necrosis after prolonged ischemia. We have investigated whether this protection
      extends to reperfusion arrhythmias occurring after a short (non-lethal) ischemic
      insult. Anaesthetized open chest rats were subjected to a 5-min occlusion of the
      left coronary artery. The incidence and duration of reperfusion arrhythmias and
      the duration of sinus rhythm were assessed in the first 5 min of reperfusion.
      Prior heat stress led to a reduction in the incidence (100-63%, P < or = 0.05)
      and duration (66.2 +/- 15.8 to 9.4 +/- 2.9 s, P < or = 0.05) of ventricular
      tachycardia and a non-significant reduction in the incidence (76-50%) and
      duration (74.3 +/- 23.4 to 42.9 +/- 24.4 s, P = 0.09) of ventricular
      fibrillation. This resulted in a significant increase in the duration of sinus
      rhythm (142.1 +/- 27.6 to 216.7 +/- 24.8 s, P < or = 0.05) and reduction in
      arrhythmia score (P < or = 0.05) in heat stressed rats compared with controls.
      This protection against reperfusion arrhythmias was associated with a two-fold
      increase in endogenous catalase activity and expression of the inducible heat
      stress protein HSP 70. Inhibition of catalase with pre-administered 3-amino
      triazole resulted in a paradoxical protection in both sham and heat stress
      hearts. We conclude that heat stress leads to protection against reperfusion
      arrhythmias; however, we have been unable to resolve whether the changes in
      catalase activity or HSP expression are the mediators of the demonstrated
      cardioprotection.

PMID- 8158666
TI  - Sarcomere shortening velocity in pressure overload hypertrophied rabbit right
      ventricular myocardium at physiological sarcomere lengths.
AB  - Earlier we noted the importance of internal loads for sarcomere shortening in
      heart muscle. Internal loading may change with hypertrophy and influence
      sarcomere shortening velocity. Therefore, we force clamped trabeculae from normal
      rabbit right ventricles and those hypertrophied due to pulmonary artery
      constriction. Diffraction of a laser (lambda = 632.8 nm) by a trabecula was used
      to measure sarcomere length (SL) in isotonic twitches. Resting SL was set at 2.36
      +/- 0.17 microns in the normal (n = 5) and 2.23 +/- 0.08 microns in the
      hypertrophied (n = 5) (+/- S.E.M.) muscles. The relationship of total stress with
      log10 sarcomere shortening velocity was linear. In the normals, log(SL/s) = 0.39
      1.32 (P(total)/P(isom)), and in hypertrophy, log(SL/s) = -0.16-0.57
      (P(total)/P(isom)). SL/s is sarcomere shortening velocity in microns/s divided by
      SL at the onset of constant force. P(total) is isotonic plus resting stress and
      P(isom) is peak total isometric stress. The hypertrophy (P(total)/P(isom))-(SL/s)
      relationship is depressed below normal at low loads (P < 0.001). Estimated
      unloaded SL/s in the normals was 2.47 and 0.69 in hypertrophy. Paired stimulation
      had no effect on normal SL/s. In hypertrophy, paired stimulation increased SL/s
      at low loads to normal levels. Thus, depressed sarcomere shortening velocity at
      low loads in hypertrophy at physiological sarcomere lengths disappeared when
      myoplasmic [Ca2+] increased. The results suggested that internal loading was
      greater than normal during shortening of hypertrophied myocardium. Increased
      myoplasmic [Ca2+] increased the number of crossbridges and reduced the load per
      crossbridge. This was a likely mechanism for the increase of sarcomere shortening
      velocity to normal levels.

PMID- 8158667
TI  - Assisting low-vision patients in Japan.
AB  - 1. Assisting low-vision patients in sitting down and in properly placing their
      heads for a slit-lamp examination is fundamental in low-vision patient care. 2.
      Ideally, chairs and other furniture in rooms used by low-vision should not be
      easily moved. Movable chairs are not stable, and thus could be dangerous,
      especially to people with low vision. Also, it is extremely important that
      objects are always placed at the same locations. 3. The staff should experience
      the difficulties encountered by low-vision patients by undergoing some of the
      same examinations that these patients undergo, and by walking while wearing some
      sort of vision reducer.

PMID- 8158668
TI  - Acanthamoeba keratitis.
AB  - 1. Acanthamoeba keratitis is an uncommon but increasingly prevalent infection
      with the potential to cause severe ocular damage. Acanthamoeba is a
      nonflagellated free-living amoeba that is ubiquitous in the environment. The most
      common type is A castellani, but A polyphagia, A rhysodes, A culbertson, and A
      hatchetti have been isolated from infected eyes. 2. Clinical features include
      foreign body sensation, blurred vision, tearing, and photophobia. There is
      minimal pain in the early stages of infection, but severe pain is a manifestation
      of the advanced stages of the disease. 3. The incidence of Acanthamoeba keratitis
      appears to be decreasing because of increased awareness, but education
      emphasizing proper lens sterilization is essential and should be carried out when
      contact lenses are first dispensed.

PMID- 8158669
TI  - Eye care and AIDS prevention for ophthalmic medical personnel.
AB  - 1. Clinical nurse specialists should use common sense precautions for infection
      control in all office procedures to prevent the spread of HIV, especially
      handwashing and proper disinfection of all instruments. 2. Nurses should be fully
      informed of the appearance and mechanism of AIDS in ocular manifestations
      (especially cotton-wool spots and retinal hemorrhages) and the effects of
      cytomegalovirus and Kaposi's sarcoma on vision. 3. Prevention of infections by
      reducing the risk appears to be the only current defense against the transmission
      of HIV.

PMID- 8158670
TI  - Preoperative evaluation and workup of the cataract and intraocular lens implant
      patient.
AB  - 1. Cataract and intraocular lens (IOL) implant surgery is the most common
      operation in ophthalmology. Much of the success of cataract and implant surgery
      depends on thorough and accurate preoperative patient counseling, testing, and
      biometric measurements. 2. The preoperative workup of cataract and implant
      surgery should include a complete ocular history and physical examination,
      patient education, preoperative testing, and informed consent. 3. Essential
      preoperative testing includes keratometric readings, ultrasound axial length of
      the eye (A-scan), and a calculation of implant power requirements using a modern
      implant formula. 4. In some circumstances, corneal endothelial cell counts,
      corneal pachymetry, and B-scan ultrasonographic scanning of the posterior segment
      will be needed. Optional testing also might include potential visual acuity (PVA)
      testing, ophthalmic photography, and corneal topographic scanning.

PMID- 8158671
TI  - Fulfilling record-keeping requirements mandated in OSHA regulations.
AB  - 1. The Occupational Safety and Health Administration (OSHA) requires
      implementation of an Exposure Control Plan (ECP) that details occupational health
      risks and how to avoid them, and documents all incidents that meet reporting
      requirements. 2. There are seven appendices that should be attached to any ECP,
      including a copy of OSHA regulations and related definitions, which is required
      by the OSHA Standard on Bloodborne Pathogens. 3. The six other appendices
      (Exposure Determination; Methods of Compliance; Post (hepatitis B)-Exposure
      Evaluation and Follow-Up; Communicating Hazards to Employees Through Training;
      Record Keeping; and Timetable of Compliance) are essential to maintenance of
      proper records and to compliance with OSHA regulations.

PMID- 8158672
TI  - A 2-month-old boy was taken to the ophthalmologist by his mother for evaluation
      of a "spot" in his left eye. Norrie's disease.

PMID- 8158673
TI  - Inventory fitting of RGP lenses.

PMID- 8158674
TI  - Head and neck cancer in 1994: a change in the standard of care.

PMID- 8158675
TI  - Do diet and androgens alter prostate cancer risk via a common etiologic pathway?

PMID- 8158676
TI  - Mind-body meld may boost immunity.

PMID- 8158677
TI  - Registries track rightward shift in colorectal cancer.

PMID- 8158678
TI  - Study suggests transfusions may increase cancer risk.

PMID- 8158679
TI  - Cultural differences shape cancer care.

PMID- 8158680
TI  - Phase III trial of initial chemotherapy in stage III or IV head and neck cancers:
      a study by the Gruppo di Studio sui Tumori della Testa e del Collo.
AB  - BACKGROUND: The standard treatment for advanced (stage III and IV) head and neck
      squamous cell carcinoma (i.e., surgery with postoperative radiotherapy in
      operable patients and radiotherapy alone in inoperable patients) has had poor
      results. A series of randomized trials of induction chemotherapy have up to now
      failed to demonstrate an improvement in survival. PURPOSE: This trial was
      designed to determine whether intensive induction chemotherapy administered
      before loco-regional treatment would improve survival of patients with advanced
      disease. METHODS: Patients had previously untreated, advanced nonmetastatic
      (stages III and IV) squamous cell carcinoma of the oral cavity, oropharynx,
      hypopharynx, and paranasal sinuses. The study design was a randomized, multi
      institutional, phase III trial. Eligible patients (n = 237) were randomly
      assigned to receive either initial chemotherapy (cisplatin and infusional
      fluorouracil) followed by loco-regional treatment (group A, n = 118) or loco
      regional treatment alone (group B, n = 119). For operable patients (group A, n =
      34; group B, n = 32), loco-regional treatment included resection followed by
      adjuvant radiotherapy. For inoperable patients, radical irradiation was performed
      with a planned dose of 65-70 Gy to involved areas. A dose of 45-50 Gy was also
      planned to the uninvolved neck or postoperatively. The statistical (log-rank)
      test was performed no earlier than 2 years after the randomization of the last
      patient. RESULTS: Seventy-one patients (60%) in group A and 67 patients (56%) in
      group B were considered free of disease after they completed the treatment
      sequence. The analysis of time to distant metastases showed an advantage for
      group A patients. (Respective 2- and 3-year values for inoperable patients were
      15% and 24% for group A versus 36% and 42% for group B, P = .04; only one
      operable group A patient had distant metastases after 49 months versus 26% [2
      years] and 31% [3 years] for operable group B patients, P = .01.) For inoperable
      patients, the combined treatment was significantly associated with an increase in
      complete remission rate (group A, 44%) as compared with radiotherapy alone (group
      B, 30%) (P = .037). Inoperable patients also benefitted from induction
      chemotherapy in terms of disease-free survival (49% and 34% for group A versus
      28% and 26% for group B; P = .06) and of overall survival (30% and 24% for group
      A versus 19% and 10% for group B; P = .04). CONCLUSIONS: When all 237 randomly
      assigned patients were analyzed, there were no significant differences in the two
      treatment strategies in loco-regional failure or in disease-free or overall
      survival, although the development of distant metastases was reduced. For
      operable patients, the only benefit from neoadjuvant chemotherapy was a
      significant reduction in the incidence of distant metastases. For inoperable
      patients, neoadjuvant chemotherapy improved local control, decreased the
      incidence of distant metastases, and improved the complete remission rate and
      overall survival. IMPLICATIONS: Confirmatory studies with effective chemotherapy
      regimens delivered for an adequate number of cycles are required.

PMID- 8158681
TI  - In vivo-in vitro correlation of myelotoxicity of 9-methoxypyrazoloacridine (NSC
      366140, PD115934) to myeloid and erythroid hematopoietic progenitors from human,
      murine, and canine marrow.
AB  - BACKGROUND: 9-Methoxypyrazoloacridine (PZA) is an anticancer agent that shows
      selectivity of action for carcinomas over leukemias. It also has nearly equal
      potency against cycling and quiescent or hypoxic and normoxic target cells. Phase
      I trials of PZA in humans are nearing completion. PURPOSE: This study was
      conducted to determine (a) if PZA is directly inhibitory to hematopoietic cells
      and, if it is, to characterize the inhibition pharmacodynamically, (b) whether
      species-specific differences in direct toxicity could explain differences in
      myelosuppression in mice, dogs, and humans, and (c) whether in vitro data
      correlate with in vivo myelosuppression data. METHODS: In vitro clonogenic assays
      of hematopoietic progenitors of myeloid and erythroid lineages from human,
      canine, and murine femoral marrow were used to measure the direct toxicity of
      PZA. Results from these assays were compared on an area-under-the-curve (AUC)
      basis to clinical myelosuppression data. RESULTS: On the basis of maximum
      tolerated concentrations, canine hematopoietic progenitors are most susceptible
      to PZA, followed by human and then murine progenitors. We found no difference in
      susceptibility to PZA toxicity between the human progenitors of myeloid and
      erythroid lineages. Both concentration and duration of exposure contribute to the
      in vitro toxicity of PZA. In contrast to antimetabolites, the in vitro toxicity
      of PZA could be minimized at a given AUC by lowering drug concentration and
      prolonging the period of exposure. On an AUC basis, the in vitro data are
      consistent with limited in vivo myelosuppression data from preclinical models and
      correlate with neutropenia data from a phase I trial. CONCLUSIONS: PZA directly
      inhibits hematopoietic progenitors, an action that is responsible for the
      myelosuppression observed in humans. Human marrow appears able to compensate for
      the loss of up to 35% of its myeloid progenitors, in that peripheral neutrophil
      counts remain unchanged at that level of loss. Although in vivo studies show that
      prolonged infusion reduces myelosuppression at a given total dose in both rodent
      and canine models, pharmacokinetic differences make it unlikely that this
      approach will benefit human patients. IMPLICATIONS: The in vitro data
      quantitatively predict the AUCs at maximum tolerated dose in preclinical models
      and human patients. Thus, in vitro clonogenic assays of myelotoxic agents can
      provide data that make both preclinical toxicology testing and clinical trial
      planning and interpretation more efficient and accurate.

PMID- 8158682
TI  - Prospective study of plasma fatty acids and risk of prostate cancer.
AB  - BACKGROUND: Although some evidence suggests that dietary fat intake is related to
      prostate cancer, epidemiologic studies have been inconsistent. PURPOSE: Our
      purpose was to assess the association between plasma lipid levels, particularly
      linoleic and alpha-linolenic acids, and the development of prostate cancer.
      METHODS: In 1982, at the start of the Physicians' Health Study, 14916 U.S. male
      physicians provided plasma samples, which were frozen at -82 degrees C. Data
      accumulated from a series of questionnaires were used to assess the intake of
      various foods. We used a nested case-control design to compare the fatty acid
      compositions in plasma from 120 men who later developed prostate cancer with 120
      matched controls who did not. Individual fatty acids were measured in plasma as a
      percentage of total fatty acids, using capillary gas chromatography. Conditional
      logistic regression models were used to obtain odds ratio estimates while
      adjusting simultaneously for the effects of one or more potential confounders.
      RESULTS: The relative risks (RRs) of prostate cancer for men in successively
      higher quartiles of plasma alpha-linolenic acid level were 3.0 (95% confidence
      interval [CI] = 1.2-7.3), 3.4 (95% CI = 1.6-7.5), and 2.1 (95% CI = 0.9-4.9),
      compared with those with levels below the detection threshold (P trend = .03).
      For linoleic acid, RRs in successively higher quartiles were 0.7 (95% CI = 0.4
      1.5), 0.8 (95% CI = 0.4-1.6), and 0.6 (95% CI = 0.3-1.3), with the lowest
      quartile as referent (P trend = .24). The effect estimates were not notably
      altered by adjustment for exercise, body mass, meat and dairy consumption, or
      other fatty acid levels in the plasma. The RR for eating red meat at least five
      times per week compared with less than once a week was 2.5 (95% CI = 0.9-6.7) and
      was little changed by adjustment for alpha-linolenic acid, although alpha
      linolenic acid levels were correlated with intake of red meat and butter. The
      association of alpha-linolenic acid levels with prostate cancer was greater among
      men with low linoleic acid and reduced meat intake. CONCLUSIONS: These results
      suggest that low plasma levels of alpha-linolenic acid might be associated with
      reduced risk of prostate cancer, independently of high meat intake. High linoleic
      acid and low marine fatty oils were not associated with increased risk, as
      previously hypothesized. IMPLICATIONS: The effects of dietary alpha-linolenic
      acid, particularly from vegetable sources, warrant further study. The effects of
      dietary linoleic acid and marine fatty acids seen in animal bioassays might not
      apply to human prostate cancer.

PMID- 8158683
TI  - High-energy shock waves enhance hyperthermic response of tumors: effects on blood
      flow, energy metabolism, and tumor growth.
AB  - BACKGROUND: The ability to kill cancerous tissue by heating is often limited by
      heat lost to flowing blood. Recent studies demonstrate that high-energy shock
      waves (HESWs), when applied to solid tumors, destroy the tumor microvasculature
      and rapidly decrease blood flow. We hypothesized that impairment of tumor blood
      flow by HESWs might result in increased effectiveness of hyperthermia treatment.
      PURPOSE: The purpose of our work was to determine whether HESWs enhance the
      response of tumors to hyperthermia. METHODS: Seventy A-Mel-3 amelanotic hamster
      melanomas were exposed to either 700 HESWs (20 kV, 80 nanofarads), local
      hyperthermia (43.3 degrees C for 30 minutes), or a combination of both. Three,
      12, or 24 hours later, tumor blood flow and adenosine triphosphate (ATP)
      concentrations were measured by [4-N-methyl-14C]iodoantipyrine autoradiography
      and quantitative ATP imaging bioluminescence, respectively. In separate
      experiments, the effects of the separate and combined treatments on tumor growth
      were studied in 52 animals. RESULTS: Combining HESWs and hyperthermia produced a
      significantly longer and more pronounced reduction of tumor and adjacent tissue
      perfusion than either HESWs or hyperthermia alone (P < .05). ATP concentrations
      were markedly reduced following HESW treatment alone and following the combined
      therapy compared with untreated controls (P < .05). Three hours after combined
      therapy, ATP concentrations were significantly below values measured after
      hyperthermia alone (P < .01). Tumor growth was delayed much more effectively by
      the combination of HESWs and hyperthermia than by either treatment alone (P <
      .001). Fifty-four percent of the animals receiving combined treatment showed
      complete local tumor cure over 52 days of observation, and 46% showed partial
      remission. CONCLUSION: The combination of HESWs and hyperthermia might be an
      effective new way of treating cancer, especially in patients who are not
      candidates for surgery. IMPLICATIONS: These results must be viewed cautiously, as
      the vasculature of human tumors seems to be less sensitive to hyperthermia than
      has been observed in experimental tumors.

PMID- 8158684
TI  - Residence time distributions of various tracers in tumors: implications for drug
      delivery and blood flow measurement.
AB  - BACKGROUND: The evaluation of rates of tumor blood flow with small, rapidly
      diffusing tracers requires an accurate model for mass transport within the tissue
      and tracer biodistribution. It is generally assumed that the whole tumor or
      several tumor regions act as well-mixed compartments, an assumption that has
      never been evaluated in tumors. PURPOSE: The purpose of this study was to assess
      the accuracy of compartmental flow models in tissue-isolated tumors. METHODS: We
      measured the residence time distributions of various tracers with the use of ex
      vivo perfusion of tissue-isolated rat R3230AC mammary tumors. This approach
      permits simultaneous, independent measurements of total blood flow and tracer
      concentrations in afferent and efferent vessels. The isolated tumors were
      perfused with Krebs-Henseleit solution, to which could be added D2O saline and
      either 3% by volume F44-E (a perfluorocarbon emulsion) or 1% by weight
      fluorescein isothiocyanate (FITC)-albumin. A pulse of D2O and one of the other
      tracers was added to the perfusing liquid, and the relative concentrations of
      both D2O and perfluorocarbon or FITC-albumin were measured in the tumor effluent.
      D2O and the perfluorocarbon were measured with an imaging spectrometer tuned to
      either 2H or 19F. FITC-albumin concentrations were measured by luminescence
      spectrometry. The results were analyzed using various compartmental models.
      RESULTS: The tracer residence time distribution deviated from that expected for a
      single well-mixed compartment. Only half of the D2O left the tumor with a time
      constant consistent with the known perfusate flow. The remainder exited the tumor
      more rapidly than expected, and neither vascular shunting nor macroscopic flow
      heterogeneity accounts for this component of the D2O flow. However, two
      compartment models provide an improved fit to the data. CONCLUSIONS: Our
      experiments demonstrate that the simple compartmental model used to estimate
      blood flow with diffusible tracers is not accurate. IMPLICATIONS: The nonideal
      blood flow found in our experiments reflects phenomena that may have important
      effects in the development of pharmacokinetic models of drug delivery to tumors.
      The accuracy of blood flow measurements, made with such techniques as nuclear
      magnetic resonance, positron-emission tomography, and computed tomography, may
      also be affected when they rely on the assumption that the tumor is a collection
      of well-mixed compartments.

PMID- 8158685
TI  - Suppression of the tumorigenic and metastatic abilities of murine B16-F10
      melanoma cells in vivo by the overexpression of the tissue inhibitor of the
      metalloproteinases-1.
AB  - BACKGROUND: Metalloproteinases participate in the first steps of tumor invasion
      and subsequent metastasis. Three distinct proteins have been identified as tissue
      inhibitors of metalloproteinases (TIMPs), and an imbalance between TIMPs and
      metalloproteinases may be an important factor in tumor progression. PURPOSE: The
      purpose of this study was to determine if increased levels of TIMP-1 suppressed
      the malignant phenotype of B16-F10 melanoma cells in mice. METHODS: We examined
      and compared the tumorigenic and metastatic behavior of B16-F10 cells, several
      independent clonal cell lines that were transfected to overexpress TIMP-1, and a
      vector-transfected control in both nude (BALB/c) and syngeneic (C56BL/6) mice.
      Tumor growth was assessed by subcutaneously injecting female nude mice with 10(5)
      cells of parental or transfected B16-F10 cell lines, and monitoring for the
      appearance of tumors at the injection site. Tumor size was measured every 2-3
      days for 5 weeks. To evaluate the effect of elevated TIMP-1 on metastases, 3 x
      10(4) cells were administered by intravenous injection into the tail vein of
      C57BL/6 mice, and the number of metastases counted on days 14 and 22. RESULTS:
      Following subcutaneous injections into nude mice, TIMP-1-overexpressing cells
      showed a substantial decline in their primary tumor growth, characterized by a
      reduced tumor incidence (50%-89% versus 100% in controls) and longer periods
      before the appearance of tumors (15 +/- 1.0 to 19 +/- 3.3 days versus 12 +/- 0.4
      days in controls). All TIMP-1 clones showed a reduction in their lung
      colonization ability (8.2 +/- 1.4 to 48.1 +/- 9.9 versus 59.9 +/- 6.0 metastatic
      nodules in controls) following intravenous injection into syngenic mice. The
      number of lung metastases arising from four of the five TIMP-1-overexpressing
      lines was significantly lower than those formed by parental or control cells.
      CONCLUSIONS: The data demonstrate that an overexpression of TIMP-1 directly
      inhibits the tumorigenic as well as metastatic potential of B16-F10 cells in
      mice, lending further support to the importance of TIMP-1 in controlling
      malignancy.

PMID- 8158686
TI  - High-dose ifosfamide-induced exacerbation of peripheral neuropathy.

PMID- 8158687
TI  - Phase II trial of 13-cis-retinoic acid plus interferon alpha in non-small-cell
      lung cancer. The National Cancer Institute of Canada Clinical Trials Group.

PMID- 8158688
TI  - Cytotoxic drugs plus subcutaneous granulocyte-macrophage colony-stimulating
      factor: can molgramostim enhance antisarcoma therapy?

PMID- 8158689
TI  - Re: Lung cancer: another consequence of a high-fat diet?

PMID- 8158690
TI  - Chemotherapy for resectable stage III non-small-cell lung cancer--can that dog
      hunt?

PMID- 8158691
TI  - Radiotherapy to the conserved breast: is it avoidable if the cancer is small?

PMID- 8158692
TI  - Reanalyses of NSABP studies. National Surgical Adjuvant Breast and Bowel Project.

PMID- 8158693
TI  - Swedish study helps usher in a new treatment era.

PMID- 8158694
TI  - Patient input blossoms from seeds of SPORE grants. Specialized Programs of
      Research Excellence.

PMID- 8158695
TI  - Quality of life adds a human dimension to studies on treatment cost
      effectiveness.

PMID- 8158696
TI  - Panel concludes ovarian cancer screening benefit unproven.

PMID- 8158697
TI  - Congressional hearing delves into NSABP fraud issues. National Surgical Adjuvant
      Breast and Bowel Project.

PMID- 8158698
TI  - A randomized trial comparing perioperative chemotherapy and surgery with surgery
      alone in resectable stage IIIA non-small-cell lung cancer.
AB  - BACKGROUND: Patients with resectable stage IIIA non-small-cell lung cancer have a
      low survival rate following standard surgical treatment. Nonrandomized trials in
      which induction chemotherapy or a combination of chemotherapy and radiation prior
      to surgery were used to treat patients with regionally advanced primary cancers
      have suggested that survival is improved when compared with treatment by surgery
      alone. PURPOSE: We performed a prospective, randomized study of patients with
      previously untreated, potentially resectable clinical stage IIIA non-small-cell
      lung cancer to compare the results of perioperative chemotherapy and surgery with
      those of surgery alone. METHODS: This trial was designed to test the null
      hypothesis that the proportion of patients surviving 3 years is 12% for either
      treatment group against the alternate hypothesis that the 3-year survival rate
      would be 12% in the surgery alone group and 32% in the perioperative chemotherapy
      group. The estimated required sample size was 65 patients in each group. The
      trial was terminated at an early time according to the method of O'Brien and
      Fleming following a single unplanned interim analysis. The decision to terminate
      the trial was based on ethical considerations, the magnitude of the treatment
      effect, and the high degree of statistical significance attained. In total, 60
      patients were randomly assigned between 1987 and 1993 to receive either six
      cycles of perioperative chemotherapy (cyclophosphamide, etoposide, and cisplatin)
      and surgery (28 patients) or surgery alone (32 patients). For patients in the
      former group, tumor measurements were made before each course of chemotherapy and
      the clinical tumor response was evaluated after three cycles of chemotherapy;
      they then underwent surgical resection. Patients who had documented tumor
      regression after preoperative chemotherapy received three additional cycles of
      chemotherapy after surgery. RESULTS: After three cycles of preoperative
      chemotherapy, the rate of clinical major response was 35%. Patients treated with
      perioperative chemotherapy and surgery had an estimated median survival of 64
      months compared with 11 months for patients who had surgery alone (P < .008 by
      log-rank test; P < .018 by Wilcoxon test). The estimated 2- and 3-year survival
      rates were 60% and 56% for the perioperative chemotherapy patients and 25% and
      15% for those who had surgery alone, respectively. CONCLUSIONS: In this trial,
      the treatment strategy using perioperative chemotherapy and surgery was more
      effective than surgery alone. IMPLICATIONS: This clinical trial strengthens the
      validity of using perioperative chemotherapy in the management of patients with
      resectable stage IIIA non-small-cell lung cancer. Further investigation of the
      perioperative chemotherapy strategy in earlier stage lung cancer is warranted.

PMID- 8158699
TI  - Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in
      colorectal adenocarcinomas.
AB  - BACKGROUND: Aberrations of the p53 gene (also known as TP53) frequently lead to
      the synthesis of mutant proteins that accumulate in the nuclei and/or cytoplasm
      of neoplastic cells. Intracellular p53 protein accumulation may be an unfavorable
      prognostic parameter in breast, lung, ovarian, gastric, and colorectal cancers.
      Specific classes of p53 gene mutations, assayed by characteristic subcellular p53
      protein accumulation patterns, may be useful prognostic indicators. PURPOSE: The
      prognostic value of nuclear and cytoplasmic p53 protein accumulation in the tumor
      cells of patients with colorectal carcinoma was studied. METHODS: Antibodies PAb
      1801 and CM1 were used for immunocytochemical assay of nuclear and cytoplasmic
      p53 protein accumulation in a retrospective series of colorectal carcinoma
      samples obtained from 206 patients who were followed for at least 5 years.
      Results were correlated with the following clinicopathologic parameters: patient
      sex and age; tumor site, stage, and grade; and DNA ploidy status of the tumors.
      Overall survival and disease-free survival were analyzed with the Kaplan-Meier
      method. Differences in distributions were analyzed using the Mantel-Cox method.
      Multivariate analysis was performed with the Cox proportional hazards model.
      RESULTS: Immunostaining with PAb 1801 revealed nuclear p53 accumulation in 46%
      (95) of 206 cases, whereas CM1 immunostaining of 197 cases showed nuclear and
      cytoplasmic p53 accumulation in 33% (65 cases) and 50% (99 cases) of the cases,
      respectively. In univariate analysis, both nuclear p53PAb 1801 and cytoplasmic
      p53CM1 protein accumulations were significantly associated with poor overall
      survival (P = .0198 and P = .0017, respectively) and with disease-free survival
      (P = .004 and P = .0016, respectively). When patients were analyzed according to
      site of their tumors, nuclear p53PAb 1801 protein accumulation was statistically
      significant only in the right colon (P = .027), whereas cytoplasmic p53CM1
      protein accumulation was statistically significant in the left colon and rectum
      (P = .0016). In multivariate analysis, only cytoplasmic p53CM1 protein
      accumulation was associated with poor overall survival and with disease-free
      survival (P = .006 and P = .002, respectively). With the addition of DNA ploidy
      status, however, cytoplasmic p53CM1 protein accumulation remained significant
      only for disease-free survival (P = .035). In patients with tumors of the left
      colon and rectum, cytoplasmic p53CM1 protein accumulation was the most
      significant prognostic indicator for overall survival (P = .007) and disease-free
      survival (P = .002) after disease stage. CONCLUSION: Cytoplasmic p53CM1 protein
      accumulation, but not nuclear p53PAb 1801 protein accumulation, is an independent
      prognostic parameter in patients with colorectal carcinomas. IMPLICATIONS:
      Cytoplasmic p53CM1 accumulation may be a useful indicator of patients at high
      risk for disease recurrence who may benefit from aggressive adjuvant therapy.

PMID- 8158700
TI  - Altered retinoblastoma protein expression and prognosis in early-stage non-small
      cell lung carcinoma.
AB  - BACKGROUND: Altered retinoblastoma (RB [also known as RB1]) gene expression was
      initially found in a small cohort study to occur in five (22%) of 23 patients
      with primary stage I and II non-small-cell lung carcinomas (NSCLCs). Putative
      mutation of the p53 gene (also known as TP53) has also been found to occur
      frequently in stage I and II NSCLCs and to be associated with more aggressive
      disease and a poorer prognosis. PURPOSE: Our purpose was to determine the Rb
      protein status in the same cohort that had been previously studied for their p53
      protein status and to document whether loss of Rb protein expression was also an
      important factor in overall survival. METHODS: One hundred one stage I or II
      NSCLC specimens were analyzed by immunohistochemical staining. These paraffin
      embedded tumor sections were obtained from individual paraffin blocks prepared
      for each patient in the previous study. Patient survival status was obtained from
      hospital and tumor registry records. RESULTS: Altered Rb protein expression was
      found in 24 of 101 stage I and II NSCLCs. The median survival was 32 months for
      patients with Rb-positive (Rb+) tumors and 18 months for individuals in whom
      expression of Rb protein was absent or altered (Rb-) in tumor cells. Log-rank
      analysis of the differences in overall survival was statistically significant (P
      = .007). When these results were combined with the p53 status in the same tumor,
      the median survival was 12 months for those individuals who had theoretically the
      worst pattern (Rb-/p53+) and 46 months for those patients with theoretically the
      best pattern (Rb+/p53-) (P < .001). The Rb+ and Rb- groups in this cohort were
      well balanced with respect to the distribution of age, disease stage, histologic
      types, p53 status, and sex. Using a multivariate proportional hazards regression
      model, both altered Rb and p53 status were found to be significantly associated
      with poor prognosis (P = .005 and .012, respectively) in the overall cohort.
      CONCLUSION: Altered Rb protein expression is an independent prognostic marker for
      overall decreased survival in early-stage NSCLC as detected by absence of nuclear
      Rb protein staining. There appears to be a poorer prognosis when loss of Rb
      protein function and mutated p53 protein occur in the same tumor. IMPLICATIONS:
      If these findings can be confirmed in larger prospective studies, the results
      would suggest that both the Rb and p53 status should be utilized as independent
      prognostic factors in early-stage NSCLC.

PMID- 8158701
TI  - Acetylator phenotype, aminobiphenyl-hemoglobin adduct levels, and bladder cancer
      risk in white, black, and Asian men in Los Angeles, California.
AB  - BACKGROUND: There is a large body of epidemiologic and experimental data that
      have identified a number of arylamines as human bladder carcinogens. Metabolic
      activation is required to biotransform these arylamines into their carcinogenic
      forms, and N-hydroxylation, which is catalyzed by the hepatic cytochrome P4501A2
      isoenzyme, is generally viewed as the first critical step. On the other hand, the
      N-acetylation reaction, catalyzed by the hepatic N-acetyltransferase enzyme,
      represents a detoxification pathway for such compounds. The N-acetyltransferase
      enzyme is coded by a single gene displaying two phenotypes, slow and rapid
      acetylators. In the United States, cigarette smoking is a major cause of bladder
      cancer in men, and carcinogenic arylamines present in cigarette smoke are
      believed to be responsible for inducing bladder cancer in smokers. PURPOSE: Our
      purpose was to test the differences in three ethnic/racial groups for the
      prevalence of acetylator phenotypes and to ascertain whether slow acetylators
      actually have higher levels of activated arylamines in comparison with rapid
      acetylators. METHODS: One hundred thirty-three male residents of Los Angeles
      County who were either white, black, or Asian (Chinese or Japanese) and over the
      age of 35 years were assessed for their acetylator phenotype and levels of 3- and
      4-aminobiphenyl (ABP) hemoglobin adducts. Subjects were either lifetime
      nonsmokers (n = 72) or current cigarette smokers of varying intensity (n = 61).
      RESULTS: The proportion of slow acetylators was highest among whites (54%),
      intermediate among blacks (34%), and lowest among Asians (14%). Similarly,
      geometric mean levels of both 3- and 4-ABP-hemoglobin adducts were highest in
      whites (1.80 and 49.2 pg/g hemoglobin [Hb], respectively), intermediate in blacks
      (1.54 and 38.5 pg/g Hb), and lowest in Asians (0.73 and 36.0 pg/g Hb). As
      expected, cigarette smokers had significantly higher mean levels of both 3- and 4
      ABP-hemoglobin adducts relative to nonsmokers, and the levels increased with the
      number of cigarettes smoked per day (P < .0005 for both adducts). Slow
      acetylators consistently exhibited higher mean levels of ABP-hemoglobin adducts
      relative to rapid acetylators, independent of race and level of smoking.
      CONCLUSION: The present cross-sectional survey supports acetylation phenotype as
      an important determinant of bladder cancer risk and a possible major factor in
      the varying bladder cancer risk among whites, blacks, and Asians.

PMID- 8158702
TI  - Sector resection with or without postoperative radiotherapy for stage I breast
      cancer: five-year results of a randomized trial. Uppsala-Orebro Breast Cancer
      Study Group.
AB  - BACKGROUND: The effectiveness of routine postoperative irradiation following
      breast-conserving treatment of breast cancer has not previously been assessed in
      randomized clinical trials that have taken place in settings where mammography
      has been a major pathway to diagnosis or that have followed patients treated
      surgically by sector resection. PURPOSE: The aim of this study was to determine
      if treatment of stage I breast cancer by strictly standardized surgical technique
      with meticulous confirmation of a complete excision can reduce the local
      recurrence rate to an acceptable level without routine adjuvant radiotherapy.
      METHODS: In this trial conducted in Sweden, 381 women with stage I breast cancer
      were surgically treated by sector resection plus axillary dissection; then 184
      women were randomly selected to receive postoperative radiotherapy to the breast
      (XRT group), and 197 women received no further treatment (non-XRT group). Patient
      accrual started in October 1981 and ended in September 1988. Criteria for
      eligibility were a unifocal cancer 20 mm or less in diameter (visible on
      mammogram) and radical excision and no histopathologic signs of axillary
      metastases. RESULTS: After median follow-up times of 65 and 63 months, the 5-year
      local recurrence rate was 2.3% (95% confidence interval [CI] = 0.1%-4.3%) in the
      XRT group and 18.4% (95% CI = 12.5%-24.2%) in the non-XRT group, respectively.
      The life-table curves were significantly different (P = .0001). The two treatment
      groups did not differ in overall survival: For the XRT group, the value was 91.0%
      (95% CI = 86.4%-95.4%); for the non-XRT group, it was 90.3% (95% CI = 85.8%
      94.8%). The same was true for survival free from regional and distant recurrence:
      XRT group, 90.0% (95% CI = 85.3%-94.5%); non-XRT group, 87.1% (95% CI = 82.3%
      92.0%). The rate of local recurrences was significantly higher in patients
      treated more recently (P. = 003). CONCLUSIONS: Sector resection plus radiotherapy
      to the breast very effectively achieves local tumor control. Surgery alone
      results in similar survival prospects, but the probability of local recurrence
      approaches 20% at 5 years. IMPLICATIONS: The increase in recurrence rate observed
      over time suggests that surgical technique and patient selection should be
      improved. The benefits of reduced cost and patient inconvenience that would
      result from the elimination of postoperative radiotherapy must be carefully
      weighed against the disadvantages of local recurrence. Longer term follow-up must
      be done to estimate the risk of cancer recurrence in these women 10 and 15 years
      later, and methods must be developed to identify those women who have a higher
      risk of recurrence. Finally, economic analyses of this and similar trials are
      needed to give empirical underpinnings for optimal use of radiotherapy.

PMID- 8158703
TI  - Prescription for physicians suffering from advocacy deficit.

PMID- 8158704
TI  - Brain injury patterns in fatally injured pedestrians.
AB  - To study the relationship between the severity of impact to the head and the
      severity and distribution of injury to the brain in fatally injured pedestrians,
      events in vehicle-pedestrian collisions were reconstructed to determine the peak
      linear and angular acceleration sustained by the pedestrians' heads. The nature
      and distribution of injuries to the brain were determined by neuropathologic
      examination of coronal sections of the brain. Study of 13 cases with occipital
      impacts and 18 with lateral impacts showed that the brain appeared to be more
      susceptible to injury from lateral impacts. The frontal and temporal regions
      appeared to be more susceptible to injury at low accelerations in occipital
      impacts, providing an explanation for "coup" and "contrecoup" injuries. For
      occipital impacts, a positive relationship was found between linear acceleration
      and the extent of injury to the brain, suggesting that there was a threshold for
      observable and concussive brain injury at about 1500 m/s2 peak linear
      acceleration. These findings are important for the development of measures for
      preventing brain injuries.

PMID- 8158705
TI  - Generalized vascular permeability and pulmonary function in patients following
      serious trauma.
AB  - It has been suggested that the adult respiratory distress syndrome (ARDS) is a
      manifestation of a generalized vascular permeability defect. Low-level urinary
      albumin excretion reflects changes in systemic vascular permeability in a variety
      of acute inflammatory conditions including trauma. To test the hypothesis that
      impaired pulmonary function is associated with increased systemic vascular
      permeability, 44 trauma patients with Injury Severity Scores (ISS) ranging from 9
      to 75 were studied over 3 days. Urinary albumin was measured from admission and
      expressed as the albumin/creatinine ratio (ACR). In 24 mechanically ventilated
      patients mean inspired oxygen/fraction (FIO2) and mean arterial oxygen tension
      (PO2) were used to calculate the PO2/FIO2 ratio. For each study day patients were
      divided into group I, mean FIO2 > 0.5; group II, mean FIO2 < 0.5; and group III,
      those breathing spontaneously. During the first posttrauma period the log ACR and
      the PO2/FIO2 ratio were inversely related (r = -0.712; p < 0.001), and the log
      ACR predicted PO2/FIO2 independent of ISS (p = 0.001). The log mean ACR (SD) for
      groups I and III were 34.0 (5.6) and 8.7 (2.9) mg/mmol, respectively (Mann
      Whitney p = 0.013). Following trauma, pulmonary dysfunction is associated with
      increased vascular permeability in remote organs.

PMID- 8158706
TI  - The role of systemic antibodies against intestinal Escherichia coli in the
      prevention of bacterial translocation of Escherichia coli in a burn model in
      mice.
AB  - Bacterial translocation (BT) from the gastrointestinal (GI) tract has been
      proposed to play a role in the pathogenesis of septic complications in severely
      burned patients. It is well known that severely ill patients such as thermally
      injured patients may acquire new potential pathogenic microorganisms in the GI
      tract. Because these patients have no antibodies directed against these acquired
      microorganisms, BT may be facilitated in these patients. To investigate this
      hypothesis in a burn model, a study was performed in which two groups of C3H-HeN
      mice underwent a different period of intestinal overgrowth by a single neomycin
      resistant (NR) Escherichia coli strain after oral neomycin-bacitracin treatment.
      Group I underwent a short period (5 days) and group II experienced a long period
      (44 days) of intestinal overgrowth before a thermal injury was executed. Two days
      postburn, plasma antibody titers of IgA, IgG, and IgM isotype against NR E. coli
      were measured by indirect immunofluorescence (IIF) and BT to various organs was
      determined by culturing. Although there were no significant differences of BT to
      organs between the groups, the IgG antibody titer against the NR E. coli strain
      was significantly increased in group II. Antibody titers of IgA and IgM were not
      significantly different between the groups. Titers of plasma antibodies of IgG
      isotype against the intestinal NR E. coli did not correlate with BT. We conclude
      that increased IgG titers against the NR E. coli used are the result of a longer
      intestinal overgrowth period and are not associated with prevented or decreased
      BT.

PMID- 8158707
TI  - Dose dependency of granulocyte-macrophage colony stimulating factor for improving
      survival following burn wound infection.
AB  - Infections remain a serious problem following injury. Immune modulation offers an
      additional strategy for the treatment of infections. We evaluated the ability of
      a multilineage hematopoietic growth factor, granulocyte-macrophage colony
      stimulating factor (GM-CSF), to improve survival following burn injury with a
      superimposed burn wound infection. Groups of 12 BDF1 mice received a 15% total
      body surface area (TBSA) thermal injury by immersion in 100 degrees C water; 6 x
      10(3) Pseudomonas was then applied to the burn wound. The GM-CSF was injected
      subcutaneously B.I.D. for 7 days. Mice receiving the 10-ng dose of GM-CSF had
      significantly improved survival compared with the controls; other doses had no
      significant effect on survival. Clinical trials to assess the ability of GM-CSF
      to reduce infectious complications following burn injury are underway and these
      data suggest selecting a specific dose may be critical in achieving maximal
      benefit.

PMID- 8158708
TI  - Conservative treatment of type III renal trauma.
AB  - Type III renal injuries, deep cortical lacerations with or without urinary
      extravasation, have traditionally been managed by exploration and surgical
      repair. With improved and readily available radiologic imaging modalities such as
      computed tomography and intravenous pyelography, we propose that the majority of
      these injuries can be followed expectantly with delayed intervention as needed.
      The records of 71 patients with both blunt abdominal and penetrating trauma with
      suspected significant renal injuries were reviewed. Eighteen patients (nine blunt
      and nine penetrating trauma) with type III injury were identified. Thirteen
      patients had their renal injuries treated conservatively and three patients
      underwent immediate surgical repair. Two patients died of associated injuries
      shortly after arrival at the emergency room. Two of the conservatively treated
      patients and one who had initial repair needed subsequent intervention, but no
      renal unit was lost because of delayed intervention. Thus, of the 16 surviving
      patients with type III injuries, 13 (81%) were successfully managed
      conservatively without the need for surgical intervention. With the aid of
      computed tomography, conservative therapy for severely injured kidneys can yield
      favorable results and save patients from unnecessary exploration and possible
      renal loss.

PMID- 8158709
TI  - Is early osteosynthesis safe in multiple trauma patients with severe thoracic
      trauma and pulmonary contusion?
AB  - The timing of osteosynthesis of major fractures in patients with multiple
      injuries is still disputed. Recently questions have been raised as to the
      possible detrimental effects of this treatment on pulmonary function in patients
      who have additional thoracic trauma. In this study the charts of 57 consecutive
      patients with multiple injuries including thoracic trauma were analyzed. Thirty
      patients without major fractures were compared with 27 patients with major
      fractures treated by early osteosynthesis. Despite a significantly higher Injury
      Severity Score (ISS) in in the group with major fractures, there was no
      significant difference in pulmonary function between the two groups. We conclude
      that the presence of thoracic trauma should not be regarded as a contraindication
      for early surgical stabilization of major fractures.

PMID- 8158710
TI  - An evaluation of expert human and automated Abbreviated Injury Scale and ICD-9-CM
      injury coding.
AB  - Two hundred ninety-five injury descriptions from 135 consecutive patients treated
      at a level-I trauma center were coded by three human coders (H1, H2, H3) and by
      TRI-CODE (T), a PC-based artificial intelligence software program. Two study
      coders are nationally recognized experts who teach AIS coding for its developers
      (the Association for the Advancement of Automotive Medicine); the third has 5
      years experience in ICD and AIS coding. A "correct coding" (CC) was established
      for the study injury descriptions. Coding results were obtained for each coder
      relative to the CC. The correct ICD codes were selected in 96% of cases for H2,
      92% for H1, 91% for T, and 86% for H3. The three human coders agreed on 222 (75%)
      injuries. The correct 7 digit AIS codes (six identifying digits and the severity
      digit) were selected in 93% of cases for H2, 87% for T, 77% for H3, and 73% for
      H1. The correct AIS severity codes (seventh digit only) were selected in 98.3% of
      cases for H2, 96.3% for T, 93.9% for H3, and 90.8% for H1. On the basis of the
      weighted kappa statistic TRI-CODE had excellent agreement with the correct coding
      (CC) of AIS severities. Each human coder had excellent agreement with CC and with
      TRI-CODE. Coders H1 and H2 were in excellent agreement. Coder H3 was in good
      agreement with H1 and H2. However, errors among the human coders often occur for
      different codes, accentuating the variability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158711
TI  - Pediatric trauma care is cost effective: a comparison of pediatric and adult
      trauma care reimbursement.
AB  - Trauma causes staggering losses: in 1987, Hermann Hospital lost $8 million to
      uncompensated trauma care. To demonstrate the survivability of pediatric trauma
      care delivery we examined reimbursement profiles for adult and pediatric trauma
      patients. We retrospectively reviewed the records of 3445 patients with serious
      trauma from October 1987 through March 1992. The group was divided into adult (>
      or = 17 years) and pediatric patients (< 17 years). We compared reimbursement
      profiles based on hospital costs generated, reimbursement, financial class,
      demographics, discharge diagnostic codes, and outcome. Significance was assessed
      by t test and Chi-square. We found a decreased length of stay (LOS) and a lower
      association with under-reimbursement or zero reimbursement in pediatric patients.
      A significantly lower percentage of pediatric patients paid none of their bill
      (17.1%) compared with the adults (23.2%). Pediatric reimbursement exceeded
      hospital costs (110.0%) compared with adult reimbursement (90.3%). This suggests
      that pediatric trauma care can survive in an atmosphere of shrinking resources.

PMID- 8158712
TI  - Measuring health status among survivors of burn injury: revisions of the Burn
      Specific Health Scale.
AB  - This study examined the reliability of a revised version of the Burn Specific
      Health Scale (BSHS). Two hundred fifty-four former patients recruited from eight
      burn centers in the southeastern United States participated in the study. Data
      were collected via chart review and mailed questionnaire. Factor analyses were
      used to identify seven subscales containing a total of 31 items. Subsequent
      analyses provided strong support for the reliability and validity of the revised
      measure. Each subscale exhibited a high level of reliability (Cronbach's alpha
      ranged from 0.82 to 0.94). Each subscale also correlated in a predictable manner
      with measures used for validation. The revised measure should improve the ability
      of both researchers and clinicians to assess the impact of non-fatal burn injury
      accurately and comprehensively.

PMID- 8158713
TI  - Comparison of the costs of acute treatment for gunshot and stab wounds: further
      evidence of the need for firearms control.
AB  - Gun control is proposed primarily to decrease the incidence of injury and death
      from gunshot wounds (GSWs). We hypothesize that decreasing the number of GSWs
      will also produce significant economic savings, even if personal violence were to
      continue at the same rate, maintaining the same overall incidence of penetrating
      trauma. We analyzed charges and reimbursements for the treatment for all patients
      with GSWs (n = 1116) and stab wounds (SWs) (n = 1529) admitted to a level I
      trauma center from 1986 through 1992. Mean and median charges were higher for
      GSWs ($14,541; $7,541) than for SWs ($6,446; $4,249) (p < 0.05). There was a 12%
      per year increase in the annual number of GSWs (p = 0.001), leading to a
      disproportionate increase in the annual total charges for GSWs (p = 0.013),
      compared with SWs. Public expenditures, including bad debt and government
      reimbursement, increased for GSWs (p = 0.019) but not SWs. Thus, if all patients
      with GSWs instead suffered SWs, there would be an annual savings of $1,290,000
      overall and of $981,000 of public funds from this institution alone. Treatment
      costs for GSWs are higher than those for SWs and are rising more rapidly, with an
      increasing amount of public funds going to meet these costs. Considerable savings
      to society would accrue from any effort that decreased firearm injuries, even if
      the same level of violence persisted using other weapons.

PMID- 8158714
TI  - Interleukin-6 and dexamethasone work coordinately to augment hepatic amino acid
      transport.
AB  - The in vivo effects of interleukin-6 (IL-6) and dexamethasone (Dex) on amino acid
      transport in rat liver were studied employing hepatic plasma membrane vesicles
      (HPMVs). Adult rats were treated with Dex (0.5 mg/kg) and subsequently with
      varying concentrations if IL-6 (10, 50, or 150 micrograms/kg). The HPMVs were
      prepared by Percoll density gradient centrifugation. The activities of System A,
      System N, and System y+ transport proteins were evaluated by tritiated uptake of
      their respective amino acids (methyl-aminoisobutyric acid [MeAIB], glutamine, and
      arginine). System A activity was increased in response to low doses of IL-6. Dex
      alone increased System A and had an additive effect to enhance transport in
      response to IL-6. System N was stimulated by higher doses of IL-6 in a dose
      dependent manner. Dexamethasone had no effect by itself on System N activity but
      worked synergistically to enhance the effect of IL-6 even at low doses. System y+
      activity was increased by Dex but IL-6 did not alter arginine transport. Kinetic
      analysis of the increases in System A and N showed the increases to be related to
      an increase in the Vmax (maximal transport velocity) for the carrier with no
      significant change in Km, carrier affinity. We conclude that IL-6 and
      glucocorticoids work in a coordinated fashion to enhance hepatic amino acid
      uptake.

PMID- 8158715
TI  - Nonoperative management of blunt hepatic trauma: the exception or the rule?
AB  - To evaluate the role of nonoperative management in the treatment of blunt liver
      trauma we examined all victims of blunt hepatic trauma admitted to our
      institution during a 36-month period under a protocol of nonoperative management.
      One hundred twenty-six patients had the diagnosis of blunt hepatic injury
      confirmed by abdominal computed tomographic (CT) scanning, surgical exploration,
      or autopsy. Twenty-four patients went to the operating room without CT scanning
      because of hemodynamic instability (16), peritoneal signs (two), or positive
      results on DPL (six). Ten other patients died of extra-abdominal trauma before
      reaching the operating room. The remaining 92 patients had CT scans of the
      abdomen. Of these 92 patients, 20 required surgery. The indications for surgery
      were hemodynamic instability (seven), peritoneal signs (six), nonhepatic injuries
      requiring surgery (five), and massive hemoperitoneum (two). Seventy-two patients
      were intentionally managed nonoperatively (55% of total liver injuries, 78% of
      scanned patients). Seventy (97%) of these patients were managed successfully
      without surgery. Of these 72 liver injuries, 11 were grade I, 28 were grade II,
      16 were grade III, ten were grade IV, and five were grade V. The transfusion
      requirement in the first 24 hours for the nonoperative group was significantly
      lower than that for the group undergoing surgery (1.2 +/- 1.7 vs. 12.2 +/- 14
      units). There were no instances of hemobilia, intrahepatic bile collections, or
      abdominal abscess in the nonoperative group. The grade of hepatic injury as
      diagnosed by CT scan does not predict the need for surgery.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8158716
TI  - Thoracoscopic drainage and decortication as definitive treatment for empyema
      thoracis following penetrating chest injury.
AB  - PURPOSE: The purpose of this study is to describe our experience with
      thoracoscopic drainage and decortication as definitive treatment for empyema
      thoracis following penetrating chest trauma. METHODS: Over a 9-month period,
      eight patients at two institutions were treated for empyema thoracis that
      developed following penetrating chest injury. Seven patients sustained gunshot
      wounds and one a stab wound. All were treated for hemothorax with a closed tube
      thoracostomy. Associated injuries included six spinal cord injuries, a liver and
      diaphragmatic injury, a subclavian injury, and a carotid injury. Each patient
      subsequently developed an empyema. All patients underwent one thoracoscopic
      drainage and decortication of the empyema. RESULTS: In all patients, complete
      resolution of the empyema was achieved with the thoracoscopic technique. Chest
      tubes were removed a median of 8.5 days after the procedure. Median blood loss
      was 200 mL. The average duration of the operation was 110 minutes. There were two
      complications, a persistent air leak and a trapped lung, both treated with
      thoracoscopic intervention. CONCLUSION: Thoracoscopic drainage and decortication
      offers an alternative to thoracotomy for definitive therapy of empyema thoracis
      developing after penetrating chest trauma.

PMID- 8158717
TI  - Comparison of acid neutralizing and non-acid neutralizing stress ulcer
      prophylaxis in thermally injured patients.
AB  - We have compared the effectiveness of non-acid neutralizing stress ulcer
      prophylaxis (SUC) with sucralfate (n = 48) with that of acid neutralizing
      prophylaxis (AN) utilizing antacids and cimetidine (n = 48) in the prevention of
      stress ulcer bleeding and nosocomial pneumonia (PN) in thermally injured
      patients. In the subset of intubated patients, the incidence of PN was 17.8% and
      42.8% in the AN and SUC groups, respectively (p < 0.05) despite a similar
      postburn time of onset of pneumonia. Ten patients in each group died. Three
      patients in the SUC group developed upper GI bleeding with one requiring
      gastrectomy. Bacterial colonization of the upper airway occurred in virtually all
      patients, whereas 83% (SUC) and 96% (AN) had colonization of gastric contents.
      Gram-negative colonization rates for the upper airway were not different (70%)
      whereas 48% of SUC patients compared with 60% of AN patients had gram-negative
      gastric colonization. In conclusion, SUC therapy was efficacious in the
      prevention of stress ulcer bleeding but did not alter the rate of bacterial
      colonization of the airway or gastric contents, and was associated with a higher
      incidence of nosocomial pneumonia in intubated patients.

PMID- 8158718
TI  - Critical care training makes trauma care more attractive as a career.
AB  - One recent report has prompted concern that surgical residents are no longer
      concerned in providing trauma care as a significant portion of their careers. In
      1986, we linked our trauma and critical care services. We surveyed all chief
      residents who finished in the past 10 years, comparing the 5 years before the
      linking of trauma and critical care to the period since. Between 1982 and 1987, 3
      of the 45 finishing residents (7%) pursued trauma fellowships, then trauma care
      as a career. Since 1987, 12 finishing residents (30% of the total and 33% of
      those pursuing fellowship training) trained in trauma/critical care. Nine
      currently pursue trauma care as a career. Two others are academic trauma surgeons
      without fellowship training and one other practices general surgery with trauma
      care as a main focus. Thus 12 of the 41 residents (30%) practice trauma care and
      14 residents (34%) practice critical care. Residents finishing since 1987 were
      significantly more likely to respond that they are interested in trauma care,
      feel trauma care was attractive, and wish to have trauma care be a major portion
      of their careers. Those who chose not to pursue trauma care cited reasons similar
      to those described by Richardson and Miller. Other specialty interests were the
      most important factor in both time periods. Residents finishing after 1987
      described the link between trauma care and critical care with a designated ICU
      service as strong positive influences. The understanding of resuscitation
      physiology gained in the ICU, including nonsurgical therapy, was felt to enhance
      trauma care, making it more attractive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158719
TI  - Limb ischemia and reperfusion: relationship of functional recovery to nerve and
      muscle blood flow.
AB  - The relative importance of nerve versus muscle injury in limb ischemia
      reperfusion is poorly understood. We used 14C-butanol tissue distribution to
      measure regional blood flow simultaneously in the proximal and distal sciatic,
      the posterior tibial nerve trunk (NBF), and biceps femoris muscle (MBF) of rats
      during 3 hours of occlusion of the ipsilateral iliac and femoral arteries and
      subsequently for up to 9 days of reperfusion. Limb motor function was also
      serially assessed. The contralateral limbs served as controls. Experimental
      groups were untreated control (n = 16); methylprednisolone, 30 mg/kg (n = 13);
      the lazaroid U74389F, 3 mg/kg (n = 13); and lazaroid vehicle (n = 13), i.v. 15
      minutes before occlusion and 15 minutes after reperfusion. RESULTS: One hour
      after occlusion, NBF was -77% of the control value (p < 0.02) but MBF was
      unchanged (control NBF 15.2 +/- 3.3, control MBF 6.3 +/- 0.9, units mL.min-1 x
      100 g-1). At both 2 and 21 hours of reperfusion, NBF was double that of control
      in all groups (p < 0.01); but MBF, which had been modestly elevated to 10.5 +/-
      0.5 at 2 hours (p < 0.01), was already normal at 21 hours in all groups. During
      days 5 to 9 of reperfusion, NBF was still numerically elevated (NS); MBF remained
      at control. Functionally, test. limb scores were always grossly abnormal during
      occlusion (range: 7.1-8.5, normal = < 2). After 1 hour of reperfusion, all test
      limb scores were improved versus occlusion (p < 0.001, Wilcoxon rank-sum).
      Subsequently, there was gradual improvement in all groups, scores at 6 days
      ranging from 1.9 to 2.5. CONCLUSION: NBF is rapidly and severely reduced during
      ischemia. During reperfusion, the hyperemic flow response in nerve is more
      prolonged than in muscle. Limb dysfunction during ischemia and reperfusion may be
      largely the result of axonal or neuromuscular junction injury or both. Neither of
      the two treatments had effects on blood flow or limb function.

PMID- 8158720
TI  - Traumatic aneurysm of the superficial temporal artery: case report.
AB  - Traumatic aneurysms of the temporal artery are uncommon, with less than 200 cases
      reported in the literature. A case resulting from a head injury from playing a
      popular new survival game known as "paintball" is presented here. A general
      review of the literature on traumatic temporal artery aneurysms is provided, as
      well as information on this new form of recreation and safety recommendations for
      "paintball" players.

PMID- 8158721
TI  - Traumatic giant aneurysm of the intracavernous internal carotid artery causing
      fatal epistaxis: case report.
AB  - A patient with a giant intracavernous carotid aneurysm usually has symptoms and
      signs of a space-occupying lesion, producing one of a variety of types of
      cavernous sinus syndromes. Epistaxis is an unusual feature in these patients. A
      patient who noted the onset of repeated arterial epistaxis 2 years after a severe
      head injury was found to have a traumatic aneurysm of the cavernous portion of
      internal carotid artery. After angiography, he suddenly developed profuse,
      pulsatile, arterial epistaxis and had a cardiopulmonary arrest. This case and a
      review of previously reported cases emphasize the importance of early cerebral
      angiography in patients with posttraumatic recurrent epistaxis.

PMID- 8158722
TI  - Delayed rupture of the spleen--myths, facts, and their importance: case reports
      and literature review.
AB  - Over a 1-year period, three patients were seen in our trauma service with delayed
      bleeding (> or = 7 days) from an initially inapparent splenic injury. This entity
      was defined as a late occurrence of signs and symptoms attributed to splenic
      injury not detected by diagnostic computed tomographic (CT) scanning during the
      initial examination. We believe that this represents an "injury in evolution"
      minor enough to go undetected on initial CT scans of the abdomen. A high index of
      suspicion and liberal utilization of imaging techniques are essential for the
      identification of delayed splenic rupture. Further multicenter studies are
      required to delineate the true incidence of its occurrence and its clinical
      significance. We conclude that "delayed rupture" of the spleen is a true clinical
      entity. The occurrence of a delayed rupture may prove hazardous to patients
      discharged early from the hospital after blunt abdominal injury. A classification
      system to assess this type of injury is suggested.

PMID- 8158723
TI  - Delayed hemorrhage with free rupture complicating the nonsurgical management of
      blunt hepatic trauma: a case report and review of the literature.
AB  - The nonsurgical approach for the management of blunt hepatic injuries is
      appropriate for a select subset of patients. An acceptable number of
      complications of the biliary tract and intraparenchymal hematomas have been
      reported. Delayed hepatic hemorrhage has been described, however, scant data are
      available in the literature to dictate management once this complication has
      developed. A review of the recent literature indicates that nonsurgical
      management of this complication remains a safe alternative.

PMID- 8158724
TI  - Early profound jaundice following blunt hepatic trauma: resolution after
      lobectomy--case report.
AB  - The patient presented herein was seen and evaluated following a motor vehicle
      crash. Although hemodynamically stable, he was found to have a liver injury and
      orthopedic trauma. Following admission he developed rapidly deepening jaundice.
      Radiographic studies demonstrated biliary pooling in the left lobe without
      antegrade obstruction. After a left hepatic lobectomy steady improvement in his
      hyperbilirubinemia was seen. Despite our inability to identify a communication
      anatomically in the resected specimen, one explanation considered was a traumatic
      fistulization between a biliary radical and an hepatic vein.

PMID- 8158725
TI  - Forgotten injury: a late benign complication of an unremoved shrapnel fragment-
      case report.
AB  - A patient is described with a mortar shell shrapnel fragment in the anterior
      compartment of the right lower leg that had been in situ for 46 years without
      causing symptoms, when a large hematoma leading to a "chocolate cyst" developed
      around it. Initially, the patient was thought to have a malignant tumor.
      Roentgenograms and CT scans showed shrapnel fragments, and the cyst was removed
      surgically. A digital subtraction angiogram ruled out any other involvement.

PMID- 8158726
TI  - Traumatic hemipelvectomy associated with contralateral hip dislocation: case
      report.
AB  - A case of a 28-year-old man surviving traumatic hemipelvectomy is presented. This
      patient is the first reported survivor in Australia of traumatic hemipelvectomy
      and one of few survivors reported in the world literature. Accurate and rapid
      early management including good resuscitation, rapid transport to the operating
      room and an aggressive team surgical approach all contributed to survival. Acute
      complications can be kept to a minimum by adhering to the approach of rapid
      resuscitation and early intervention by a team of surgeons. Associated
      dislocation of the contralateral hip with sciatic nerve damage and subsequent
      heterotopic calcification has not been previously reported and presents a
      significant obstacle to rehabilitation. Early attention to the psychological
      status of the patient and early involvement of rehabilitation specialists is
      advocated.

PMID- 8158727
TI  - Gangrenous streptococcal myositis: case report.
AB  - Streptococcal infection of the large skeletal muscles is a rare but often rapidly
      fatal condition that may occur for no apparent reason. Nonsteroidal anti
      inflammatory drugs may have an adverse effect on outcome. A high index of
      suspicion is the key to early diagnosis.

PMID- 8158728
TI  - Compressed air injury of the colon complicated by rhabdomyolysis: case report.
AB  - We present a case of traumatic injury of the colon by compressed air. Elevated
      levels of urinary myoglobin, creatinine phosphokinase, lactate dehydrogenase, and
      glutamic oxaloacetic transaminase indicating rhabdomyolysis were noted. In this
      type of injury, rhabdomyolysis related to acute peripheral circulatory failure
      may occur because of obstruction of venous return to the heart following a great
      increase in intraperitoneal pressure.

PMID- 8158729
TI  - Ureteric rupture in an elderly patient following minor trauma: case report.
AB  - A 75-year-old woman arrived at our hospital 2 weeks after falling from a bus. She
      was shown to have a ruptured left ureter. After drainage of a urine collection
      and decompression of her obstructed kidney she recovered. To our knowledge
      ureteric rupture has not before been reported as a consequence of such minor
      trauma.

PMID- 8158730
TI  - Pubic osteolysis simulating a malignant lesion: case report.
AB  - A case of posttraumatic osteolysis of the pubic bone simulating a malignant
      lesion in a 55-year-old woman is reported. A review of the literature revealed
      that all reported cases occurred in post-menopausal women, associated with
      radiologic evidence of osteoporosis and a history of slight trauma. Biopsy was
      performed because of the possible malignant nature of the lesion, which should be
      suspected in all post-menopausal women with a destructive lesion of the pubic
      bone.

PMID- 8158731
TI  - Traumatic atlantoaxial distractive instability: case report.
AB  - We present an uncommon case of traumatic atlantoaxial distractive instability
      which manifested itself clinically in a respirator-dependent quadriplegic. The
      initial radiographic finding was anterior atlantoaxial dislocation. The patient
      was managed initially by halo traction and, 8 weeks later, demonstrated
      occipitocervical fusion with gratifying results.

PMID- 8158732
TI  - An unusual complication of a fractured femur in a child: case report.
AB  - Comminuted femoral fractures are uncommon in children. Described is a case of a 5
      year-old child with a comminuted femoral fracture with displacement of the
      fragments in the anterior abdominal wall.

PMID- 8158733
TI  - Otosyphilis: diagnostic and therapeutic update.
AB  - The thorough investigation of patients presenting with sudden or fluctuating
      hearing loss, ringing or vertigo includes serology to exclude otosyphilis.
      Treatment of otosyphilis with penicillin and corticosteroids has achieved
      improvement in hearing, tinnitus and vertigo, but not in all patients. Selecting
      which patient with positive serology will benefit from treatment remains a
      difficult clinical problem. All patients presenting to The New York Eye and Ear
      Infirmary with cochleovestibular dysfunction of unknown aetiology and positive
      syphilis serology were assumed to have otosyphilis and were treated with
      intravenous penicillin, if non-allergic, and steroids. Lumbar puncture and HIV
      testing were performed. Eighteen patients were treated. Hearing (SRT and/or
      discrimination) improved in 4 of 16 patients with hearing loss (25%), tinnitus
      decreased in 10 of 14 (71%) and dysequilibrium improved in 6 of 9 (66%). Factors
      associated with a good response included fluctuating symptoms, especially
      hearing, hearing loss less than five years, and age less than 60. Improvement was
      unrelated to the severity of the loss or previous therapy. Patients with CSF
      abnormalities, including two patients with HIV disease, had subjective
      improvement. A summary of our results and a treatment protocol are presented.

PMID- 8158734
TI  - Pulsatile tinnitus and dural arteriovenous fistula of the transverse sinus.
AB  - A case of dural arteriovenous fistula of the transverse and sigmoid sinus
      presenting with a pulsatile tinnitus is described. On the basis of this
      demonstrative case, we review the clinical presentation, pathogenesis, diagnostic
      imaging and principles of treatment of this disease. Emphasis is put on the
      importance of careful diagnostic evaluation because of potential cerebrovascular
      complications associated with dural fistulas.

PMID- 8158735
TI  - An aneurysm of the external carotid artery presenting as a parotid mass: a case
      report.
AB  - An aneurysm is infrequently the cause of a parotid mass. This report describes an
      intraparotid aneurysm of the external carotid artery which presented as an
      enlarging parotid mass. Investigation and therapeutic embolization are discussed.

PMID- 8158736
TI  - Septic internal jugular vein thrombosis.
AB  - Septic Internal Jugular Vein Thrombosis (SIJVT) is a rare but potentially life
      threatening condition which necessitates early clinical recognition and rapid
      administration of appropriate therapy. Although termed by some authors a
      "forgotten disease" in the antibiotic era, this entity is still present but
      frequently overlooked. Deep neck infections, Lemierre syndrome, central venous
      catheterization and mastoiditis are the etiologies in this series. The diagnosis
      of SIJVT utilized CT and Doppler ultrasound imaging. The treatment included
      aggressive abscesses, necrotizing fasciitis, mastoiditis). Anti-coagulant agents
      were used in order to reduce the risks of pulmonary embolism.

PMID- 8158737
TI  - Problem-based learning: perspectives for otolaryngology--head and neck surgery.
AB  - The concept of problem-based learning (PBL) is sweeping through many schools of
      medicine in North America. Medical curricula are undergoing significant changes
      to reflect this learning philosophy. This paper analyzes the rationale behind
      this approach with emphasis on its impact on the teaching of otolaryngology--head
      and neck surgery in both the undergraduate and postgraduate levels. The "new
      pathway" curriculum of Harvard Medical School forms the basis for discussion. The
      University of Ottawa's new "Curriculum 2000" inaugurated in September 1992 is
      presented. An open-minded approach to the dramatic changes may reap unexpected
      benefits for the "orphan specialties" including our own.

PMID- 8158738
TI  - Introduction of a Canadian dollar coin has created a new health hazard for
      children.
AB  - Coins have remained at the top of the incidence list of published series of
      endoscopic removal of pediatric foreign bodies. The introduction of the Canadian
      dollar coin in 1987 has presented another hazard for children. A total of 228
      consecutive pediatric patients that underwent esophagoscopy for removal of
      foreign body from 1979 to 1989 are reviewed. Esophagoscopy under general
      anesthesia is the safest technique for the removal of impacted foreign bodies in
      the esophagus.

PMID- 8158739
TI  - Tracheotomy in the first year of life.
AB  - Tracheotomy in infants is considered to be associated with a high complication
      rate. This study was conducted to establish the indications and complications
      associated with tracheotomy in patients less than one year old. The charts of 44
      consecutive infants operated on between 1982 and 1991 at the Montreal Children's
      Hospital were reviewed. The intra-operative complication rate was 9%; the
      postoperative was 18%. Home care was associated with a very low morbidity. The
      mortality attributable to tracheotomy was 5%. Significant complications were
      associated with the lack of availability of the correct size tracheotomy cannula.
      This study finds a significant rate of complications in the infant age group, but
      differs from other studies in finding that very premature neonates do not
      experience a higher rate of complications.

PMID- 8158740
TI  - Speaking proficiency after primary tracheoesophageal puncture.
AB  - Nineteen patients who had undergone total laryngectomy with primary
      tracheoesophageal puncture underwent comprehensive testing of speaking
      proficiency. All patients learned to use tracheoesophageal speech in the
      immediate postoperative period. Overall, their speech was judged as highly
      intelligible in both objective and subjective testing when assessed by a panel of
      naive judges. Eighty per cent of all patients were easily understood on the
      telephone by a naive listener. During conversational speech, quantitative
      parameters such as vocal amplitude and fundamental frequency were similar to
      normal speakers. However they demonstrated limitations in vocal range and in peak
      amplitude when singing or shouting. The ability to produce high quality
      tracheoesophageal speech from the immediate postoperative period improves quality
      of life and expedites the overall rehabilitation after total laryngectomy.

PMID- 8158741
TI  - Fabricated single lumen tracheal cannula for a morbidly obese patient.
AB  - Morbidly obese patients who manifest upper airway obstruction or pulmonary
      insufficiency may require tracheostomy to ensure patency or provide ventilatory
      support, respectively. In this patient population the girth of the neck region
      may preclude use of currently available manufactured standardized tracheostomy
      tubes. Reported herein is the fabrication of a tracheal cannula with bisociation
      of an uncuffed endotracheal tube and the "swivel neck plate" of a tracheostomy
      tube, to provide a secure and comfortable single lumen tracheal prosthesis to
      accommodate such a patient's unique anatomy. The technique is applicable to other
      clinical scenarios if standard marketed tracheostomy tubes do not suffice.

PMID- 8158742
TI  - Ambulatory tonsillectomy and adenoidectomy: complications and associated factors.
AB  - This is a case-control study of over 500 cases of tonsillectomy and
      adenotonsillectomy performed at the Montreal Children's Hospital over a 10-month
      period. Demographics of patient population and selection criteria for out-patient
      procedure are presented. The hot (cautery) and cold (knife) dissection techniques
      are compared. Complications including intraoperative and postoperative hemorrhage
      are presented. The recognition of aerodigestive tract complications necessitating
      re-admission or emergency room management cannot be over emphasized. Recent
      history of upper airway infection (UAI) was noted to be associated with
      postoperative aerodigestive tract complications. The triad of UAI, knife
      dissection technique and increased intraoperative bleeding was found to be
      associated clinically and statistically with primary postoperative hemorrhage.

PMID- 8158743
TI  - Disturbed speech intelligibility in noise despite a normal audiogram: a defect in
      temporal resolution?
AB  - Patients with complaints of disturbed speech intelligibility in noise, despite
      normal standard audiograms, constitute a unique yet not uncommon population of
      listeners. The literature on this patient group is reviewed, and the term
      Idiopathic Discriminatory Dysfunction (IDD) is introduced in an attempt to
      standardize and qualify the distinct characteristics of this entity. Preliminary
      studies of these patients have hypothesized both frequency and temporal
      resolution deficits underlying this impairment. A representative group of 15
      patients suffering from IDD were tested using a new speech-in-noise paradigm
      designed to test temporal resolution. These patients were found to have near
      normal temporal resolving capacity as determined by this task.

PMID- 8158744
TI  - Horner's syndrome following a thyroidectomy.
AB  - A case of Horner's syndrome following a thyroidectomy for a benign multinodular
      goiter is presented, the literature reviewed, and possible explanations are
      discussed. Theories to explain this phenomenon include: local trauma to the
      sympathetic chain during retraction of the carotid sheath, anatomical variations
      which leave a patient susceptible to damage to the sympathetic chain,
      postoperative hematoma compressing the sympathetic chain, and ischemic damage to
      the sympathetic chain.

PMID- 8158745
TI  - First brachial cleft sinuses: an analysis of current management strategies and
      treatment outcomes.
AB  - First branchial cleft sinuses account for less than 1% of all branchial cleft
      anomalies. A thorough understanding of the embryology and developmental anatomy
      is essential for successful management. Nine cases of first branchial cleft
      sinuses treated at The Hospital for Sick Children by the Department of
      Otolaryngology between 1984 and 1990 were reviewed. A large proportion of these
      lesions were initially misdiagnosed despite significant symptomatology. This
      resulted in a high rate of infectious complications. Early diagnosis, prompt
      control of infection, and early surgical excision are recommended. Current
      methods of diagnosis and treatment are discussed along with techniques for facial
      nerve preservation.

PMID- 8158746
TI  - The future of performance-related sports biomechanics research.
AB  - An overview of performance-related research in sports biomechanics is presented
      describing the relevant techniques of data analysis and data processing together
      with the methods used in experimental and theoretical studies. Advances in data
      collection and processing techniques which are necessary for the future
      development of sports biomechanics research are identified. The difficulties
      associated with experimental studies in sports biomechanics are described with
      examples of the different approaches that have been used. The strengths and
      weaknesses of theoretical studies are discussed with examples drawn from a number
      of sports. It is concluded that progress in performance-related research will
      result from the application of a suitable combination of theoretical and
      experimental approaches to those sports in which technique is the primary
      requirement for success.

PMID- 8158747
TI  - A review of research in sports physiology.
AB  - The physiology of sport encompasses a wide and diverse range of scientific
      interests. The intention, and major challenge of the review, is to collate the
      most pertinent of these interests into a coherent strategy for future research in
      sports physiology. The unifying concept of this review is the potential
      contribution of future research in sports physiology to the development of the
      elite competitor. The review promotes this theme through an indepth appraisal of
      current knowledge and identification of key areas of research that would most
      profitably advance the understanding and application of sports physiology.
      Central to this theme are the physiological limitations to exercise performance
      of the elite competitor and the adaptation of these physiological systems to
      further training, possibly leading to overtraining. Indeed, the potential to
      adapt to, or recover from, the ever increasing demands of training and
      competition is considered in sections on the development of strength and power,
      the child athlete and the limitations to performance in multiple sprint
      activities such as hockey and football. Throughout the review it is recognized
      that sports physiology is increasingly reliant upon advances in analytical
      techniques and quantitative measurement. Physiological measurement, the validity
      and accuracy of present and future procedures, and the correct interpretation of
      these data are therefore considered in detail in the final section of the review.

PMID- 8158748
TI  - Current issues and future directions for performance-related research in sport
      psychology.
AB  - Thirty-seven British and international sport psychologists were asked to nominate
      performance-related issues that they considered to be priorities for research
      over the next 5-10 years. Their responses were subjectively categorized into
      seven different domains of sport psychology: motivational issues in performance;
      aspects of skill acquisition and motor control that might influence the
      attainment of excellence; stress and performance; interpersonal issues and group
      dynamics; the implications for well-being of the pursuit of excellence;
      psychological skills training; and the role of the sport psychologist. Each of
      these domains was then reviewed in order to confirm the research issues that had
      been nominated and identify any other outstanding issues that had not been
      nominated. Although it was not possible to provide detailed literature reviews
      because of page restrictions, every attempt was made to offer sufficient evidence
      to provide a clear rationale for each research issue, and enable the interested
      reader to trace all the necessary research literature.

PMID- 8158749
TI  - Future directions for performance-related sports science research: an
      interdisciplinary approach.
AB  - The present paper is based on a review which was commissioned by the Sports
      Council (London) on behalf of the Open Section of the British Association of
      Sports Sciences (BASS). This was one of four such reviews which were collectively
      designed to provide information pertinent to the formulation of a strategy that
      would guide fundamental sports science research in the UK until the year 2000.
      All of the reviews were expected to focus on research that was relevant to the
      performance of the elite athlete and the specific brief of the Open Section
      Review was to concentrate on interdisciplinary research. The current paper
      established the unique value of interdisciplinary sports science research. Four
      themes were considered in some detail in order to review the extant
      interdisciplinary research and propose directions for future research involving
      an interdisciplinary approach. The four topics were talent identification,
      adherence, injuries and peaking. A critical review of each area revealed a lack
      of interdisciplinary research and recommendations for future research priorities
      were made. The paper is concluded with a brief outline of a strategy that would
      facilitate the development and expansion of interdisciplinary sports science
      research.

PMID- 8158750
TI  - Macro-orchidism: a clinicopathological approach.

PMID- 8158751
TI  - Lymphoma of genitourinary tract.

PMID- 8158752
TI  - Outcome after temporary vascular occlusion for the management of renal trauma.
AB  - To determine the impact of temporary vascular occlusion on patient outcome after
      surgery for renal trauma, we reviewed the records of 30 patients managed since
      1977 whose injuries represented 17% of a total of 181 injuries in 175 patients.
      Reconstruction was judged to be adequate in 25 patients, while the remaining 5
      underwent immediate nephrectomy. Compared with patients whose renal injuries did
      not require temporary occlusion, these 30 were more likely to have renovascular
      trauma, shock at presentation and higher transfusion requirements.
      Postoperatively, of 20 patients renal imaging (9) and radionuclide scanning (11)
      demonstrated preservation of significant renal parenchyma or function in 18
      (90%). Although complications were more common in patients whose renal injuries
      required temporary vascular occlusion, only 2 were related to the renal injury or
      its method of repair (urinary extravasation in 1 patient and azotemia in 1 with
      bilateral injury). Temporary vascular occlusion can be performed expeditiously
      and safely, and may have an important role in preserving renal function. Our
      results support the routine use of early vascular control and the selective use
      of temporary vascular occlusion in renal injuries requiring exploration.

PMID- 8158753
TI  - Prognostic value of histological grade and nuclear grade in renal adenocarcinoma.
AB  - We conducted a retrospective study of 237 cases of clinically localized renal
      adenocarcinoma treated at our department between November 1971 and December 1991
      by radical nephrectomy. The parameters considered were tumor extension (pT
      stage), histological grading and nuclear grading. If the histological grade
      proved to be of little informational value in regard to survival, nuclear grade
      and pT stage had significant impact. On the other hand, nuclear grading
      considered in a given stage provided no significant influence. We conclude that
      nuclear grading cannot predict the outcome of patients at the same surgical
      stage.

PMID- 8158754
TI  - Complications of nephron sparing surgery for renal tumors.
AB  - The technical results of 259 nephron sparing operations for renal cell carcinoma
      or renal oncocytoma were reviewed. Local or renal related complications occurred
      after 78 procedures (30.1%). The incidence of complications was less for
      operations performed after 1988 (22% versus 37%, p = 0.009) and for incidentally
      detected versus suspected tumors (p = 0.009). The most common complications were
      urinary fistula formation (45 operations) and acute renal failure (33).
      Significant predisposing factors for urinary fistula formation included central
      tumor location (p = 0.001), tumor size greater than 4 cm. (p = 0.001), the need
      for major reconstruction of the collecting system (p = 0.001) and ex vivo surgery
      (p = 0.001). Only 1 urinary fistula required open operative repair, while the
      remainder resolved either spontaneously (30) or with endoscopic management (14).
      Significant predisposing factors for acute renal failure included a solitary
      kidney (p = 0.001), tumor size greater than 7 cm. (p = 0.008), greater than 50%
      parenchymal excision (p = 0.001), greater than 60 minutes of ischemia time (p =
      0.035) and ex vivo surgery (p = 0.001). Acute renal failure resolved in 28
      patients, of whom 9 required temporary dialysis, while 5 required permanent
      dialysis. Overall, 8 complications (3.1%) required repeat open surgery for
      treatment while all other complications resolved with noninterventive or
      endourological management. Surgical complications contributed to an adverse
      clinical outcome in only 7 patients (2.9%). Nephron sparing surgery can be
      performed safely with preservation of renal function in most patients with renal
      tumors.

PMID- 8158755
TI  - Factors influencing adrenal metastasis in renal cell carcinoma.
AB  - The factors predisposing to adrenal metastasis in renal cell carcinoma were
      reviewed in 695 cases. The overall incidence of adrenal metastasis was 4.3%. The
      risk of adrenal metastasis correlated with tumors that were on the left side,
      large and replacing the entire kidney, upper pole in location and of advanced T
      stage. Nevertheless, microscopic and/or contralateral adrenal metastasis was
      noted in patients with smaller, lower pole or mid renal tumors. Of 30 patients
      with adrenal metastasis 9 (30%) had clinical evidence of widespread disease.
      Among the patients who underwent complete surgical resection 14% had either
      positive lymph nodes or other non-adrenal metastases. Of the patients undergoing
      resection 81% died, with a mean postoperative survival of 27 months. Sustained
      disease-free survival was noted in 3 patients (0.43% of the entire series) whose
      complete pathological staging was pT1-3b, N0, M0. The need and benefit of
      adrenalectomy during surgery for renal cell carcinoma are extremely limited.

PMID- 8158756
TI  - Ureteroscopy: an outpatient procedure?
AB  - Ureteroscopy is used in the diagnosis and treatment of many urological
      conditions. The technique of ureteroscopy has been simplified by the introduction
      of smaller ureteroscopes and by an increase in the variety of accessory
      instruments that can be passed through the ureteroscope. Despite those advances,
      recent reports indicate that ureteroscopy is still generally considered an
      inpatient procedure. Since 1987 we have performed most of our ureteroscopic
      procedures on an outpatient basis. We reviewed the records of 176 patients who
      underwent ureteroscopy between 1988 and 1990, of whom 84 (47.7%) underwent
      extracorporeal shock wave lithotripsy with the same anesthesia. We treated 134
      patients (76.1% of the total group) as outpatients, while 20 (11.4%) chose to
      remain in the hospital overnight for personal reasons, 10 (5.7%) required
      additional surgery after ureteroscopy and 12 (6.8%) required hospitalization for
      preexisting medical problems or for problems that resulted from ureteroscopy. Of
      the 134 patients who were discharged from the hospital on the day of ureteroscopy
      only 4 (3.0%) required rehospitalization. The addition of extracorporeal shock
      wave lithotripsy to ureteroscopy during the same period of anesthesia did not
      increase the need for hospitalization. Ureteroscopy should be considered an
      outpatient procedure. The decision to hospitalize a patient after ureteroscopy
      should be based on preexisting medical problems or on problems that result from
      ureteroscopy. Routine hospitalization for observation is unnecessary.

PMID- 8158757
TI  - W-stapled ileal neo-bladder formed entirely with absorbable staples.
AB  - Orthotopic bladder replacement after total cystoprostatectomy for bladder cancer
      has gained broader use. Continent diversion has historically increased the
      complexity of the surgical procedure, often discouraging its adoption by many
      urologists. Absorbable staples on a GIA* instrument became available in 1992 and
      have been incorporated into reservoir formation in this preliminary study. A
      novel W-shaped ileal reservoir entirely fashioned from absorbable staples using
      the GIA and TA instruments has been developed and used in 15 patients undergoing
      cystoprostatectomy. The advantages of this technique are its simplicity and the
      speed with which the reservoir can be fashioned. In the first 15 patients
      operative time to construct the reservoir ranged from 12 to 21 minutes.
      Functional aspects of urodynamic studies and continence appear comparable to
      those of other ileal reservoirs. These preliminary data justify comparative
      trials on an expanded scale.

PMID- 8158758
TI  - A novel uretero-ileal reimplantation technique: the serous lined extramural
      tunnel. A preliminary report.
AB  - A novel technique for an anti-refluxing uretero-ileal reimplantation entailing
      creation of 2 serous lined extramural tunnels in a detubularized ileal W-bladder
      is presented. The operation was done on 12 patients in whom an orthotopic bladder
      substitute was indicated. Mean followup was 18 months. Evidence indicated that
      this method could provide a nonobstructed unidirectional flow of urine in all of
      the examined renal units.

PMID- 8158759
TI  - Interleukin-1B: a clinically relevant urinary marker.
AB  - Urinary cytokines as markers for the intravesical inflammatory response have
      become an active area of research. Interleukin-1b, a well studied and early
      produced cytokine in the immune recognition cascade, was evaluated. After
      extensive analysis of 56 control and study group urine samples, a simplified and
      reliable protocol for the preparation of urine before cytokine analysis was
      devised. The application of an available serum interleukin-1b enzyme-linked
      immunosorbent assay kit for urinary interleukin-1b analysis was then tested.
      Finally, a reference value for interleukin-1b in normal human urine was
      established and urinary interleukin-1b was measured in various bladder diseases.
      The normal and interstitial cystitis groups showed no interleukin-1b elevation.
      Significant elevation of urinary interleukin-1b was found in patients with
      bacterial cystitis compared to the interstitial cystitis and control groups (p <
      0.001). Of the patients with bladder tumors 58% showed elevation of urinary
      interleukin-1b (p < 0.001). Urinary interleukin-1b may be used as a marker to
      distinguish between bacterial and interstitial cystitis. The absence of urinary
      interleukin-1b in interstitial cystitis argues against an immunological or
      autoimmune etiology of the disorder. This study represents an important
      methodological approach to cytokine subtyping of bladder diseases.

PMID- 8158760
TI  - Synchronous management of anastomotic contracture and stress urinary incontinence
      following radical prostatectomy.
AB  - Of 77 patients presenting for artificial urinary sphincter implantation due to
      incontinence following radical prostatectomy 26 had a significant associated
      urethrovesical anastomotic contracture. Synchronous endoscopic contracture
      incision with electrocautery and implantation of an artificial urinary sphincter
      (AMS800) were performed in all cases. A total of 25 patients void with a good
      subjective flow, with an average followup of 32 months. In 1 patient symptomatic
      stenosis recurred 6 months after incision and reincision was successful at the
      time of sphincter revision. No infection or erosion developed and 24 patients are
      socially continent (0 to 1 thin pad per day). During this time 5 patients
      underwent 8 revisions of the artificial sphincter. Synchronous contracture
      incision with electrocautery and artificial urinary sphincter implantation are
      safe and provide satisfying results in patients with complex post-prostatectomy
      incontinence.

PMID- 8158761
TI  - Anatomy and strength of the tunica albuginea: its relevance to penile prosthesis
      extrusion.
AB  - In 7 male cadavers the anatomical structure, thickness and tensile strength of
      the tunica albuginea of the penis, measured at specific locations, were
      determined. The tunica is composed of inner circular and outer longitudinal
      layers made up of collagen bundles. The outer layer appears to determine, to a
      large extent, the variation in thickness and strength of the tunica. The ventral
      groove (found between the 5 and 7 o'clock positions), which houses the corpus
      spongiosum, lacks outer bundles and appears vulnerable to perforation. The
      thickness of the tunica measured at the 7, 9 and 11 o'clock positions was 0.8 +/-
      0.1 mm, 1.2 +/- 0.2 mm and 2.2 +/- 0.4 mm, respectively. Differences in the
      thickness of the tunica at specific locations were statistically significant (all
      p < or = 0.018). Symmetrical measurements were nearly identical in a mirror image
      arrangement (3, 5 and 1 at the 9, 7 and 11 o'clock positions, respectively). The
      stress on the tunica at penetration (breaking point pressure) measured at the 7,
      9 and 11 o'clock positions was 1.6 +/- 0.2 x 10(7) N/m.2, 3.0 +/- 0.3 x 10(7)
      N/m2 and 4.5 +/- 0.5 x 10(7) N/m.2, respectively. The strength and thickness of
      the tunica correlated in a statistically significant manner with location (r =
      0.911 and p = 0.0001). The most vulnerable area is on the ventral aspect (which
      lacks the longitudinally directed outer layer bundles), where most prostheses
      tend to extrude. This finding supports our belief that prosthesis extrusion often
      has an anatomical basis and is not merely a phenomenon caused by infection or
      compression.

PMID- 8158762
TI  - Preexisting vascular pathology in donor and recipient vessels during penile
      microvascular arterial bypass surgery.
AB  - The quality of the anastomosed vessels before vascular grafting has been shown to
      influence long-term patency rates in arterial reconstructive procedures. A study
      was designed to assess vascular graft quality during microvascular artery bypass
      procedures for impotence, correlate identified vasculopathy with the clinical
      history and gain insight into vascular pathophysiological mechanisms. A total of
      194 donor or recipient vessel segments was biopsied in 111 patients with
      impotence who underwent microvascular artery bypass surgery during a 10-year
      period. A prospective histological grading system was used in a blinded
      randomized fashion. A preexisting vascular pathological condition was identified
      in 48% of the patients. Proliferative lesions above the internal elastic lamina
      with luminal stenosis were identified in 38 of 69 dorsal penile artery segments
      (55%) and 8 of 69 inferior epigastric artery segments (12%). Venous hypertrophy
      or sclerosis was observed in 13 of 56 deep dorsal vein segments (23%). Systemic
      atherosclerosis was likely the underlying pathophysiology of vascular disease in
      the inferior epigastric artery. Vasculopathy in the deep dorsal vein and the
      dorsal penile artery segments was probably related to the consequences of blunt
      trauma to the pelvis, perineum or penis, which was considered to occur following
      direct vessel wall injury with immediate or delayed vascular disease or indirect
      vessel wall injury secondary to proximal arterial occlusion and delayed distal
      vascular disease. Future studies are needed to investigate the relationship
      between preexisting graft vasculopathy in microvascular artery bypass surgery for
      impotence and long-term clinical success rates.

PMID- 8158763
TI  - Topical minoxidil in the treatment of male erectile dysfunction.
AB  - Topically applied 2% minoxidil solution has been reported to increase diameter,
      rigidity and arterial flow to the penis. As a result it has been suggested as a
      possible treatment for erectile dysfunction. A total of 21 patients received 2%
      minoxidil for treatment of erectile dysfunction with instructions to apply 1 cc
      of the solution slowly over the glans penis 20 minutes before intercourse.
      Average patient age was 52.5 years (range 29 to 65 years). The etiology of the
      impotence was neurogenic in 8 patients, vascular in 7, psychogenic in 4 and other
      causes in 2. Two patients also had clinical evidence of venous incompetence and 4
      were diabetics. One patient with psychogenic impotence noticed improvement in the
      duration of erection but no increase in rigidity or size after minoxidil
      application. One patient with impotence after excision of a Peyronie's plaque
      reported a rigid erection adequate for intercourse after using minoxidil. This
      patient subsequently was able to achieve erections without using minoxidil. The
      remaining 19 patients had no improvement in erectile rigidity, or the ability to
      obtain or maintain an erection. One patient did notice some mild burning on the
      glans penis after applying the minoxidil. No other side effects were noted in any
      patient. These results indicate that 2% topical minoxidil solution is not
      effective when applied to the penis in the treatment of erectile dysfunction. It
      is possible that a higher concentration, a different delivery medium or a
      different chemical composition may yield better results.

PMID- 8158764
TI  - Pharmacokinetics of vasoactive substances administered into the human corpus
      cavernosum.
AB  - The pharmacokinetics of vasoactive substances injected into the corpus cavernosum
      for the treatment of erectile dysfunction have not been investigated to date. We
      measured the local intracavernous and peripheral venous concentration curves of
      papaverine and prostaglandin E1, and its primary metabolite 15-keto-13,14-dihydro
      prostaglandin E1 in an intra-individual comparison after intracavernous
      injection. Papaverine was measured with high performance liquid chromatography
      and prostaglandin E1 was measured with a specially adapted radioimmunoassay. The
      results demonstrate that papaverine is slowly draining into the systemic
      circulation, showing slightly elevated levels in the peripheral blood 30 and 60
      minutes after injection. Prostaglandin E1 shows a much faster decrease in local
      concentrations with no measurable increase in the periphery, probably due to the
      short half-time after lung passage. Measurement of the primary metabolite proves
      a local degradation of prostaglandin E1 in the corpus cavernosum into the
      biologically inactive 15-keto-13,14-dihydro-prostaglandin E1, which also shows a
      slight increase in the peripheral circulation due to the longer half-time of
      approximately 8 minutes. The data provide good explanation for the clinical
      finding of a markedly decreased incidence of priapism with the use of
      prostaglandin E1, which can be shown to be locally metabolized, compared to
      papaverine, which is retained in the corpus cavernosum in cases of nonvenogenic
      impotence.

PMID- 8158765
TI  - Arterial priapism: diagnosis, treatment and long-term followup.
AB  - We report on the long-term followup of 7 patients 11 to 50 years old treated for
      arterial priapism following perineal or penile trauma with arteriographic
      evidence of contrast medium extravasating from a lacerated cavernous artery into
      surrounding erectile tissue lacunae (an arterial-lacunar fistula). All patients
      underwent medical record review and completed a mailed questionnaire. The
      priapism erections were described as devoid of pain or tenderness, incompletely
      but constantly rigid and able to increase rigidity with sexual stimulation.
      Bright red corporeal aspirates were observed in all cases. Color flow Doppler
      ultrasound findings of focal areas of high flow turbulence correlated with
      diagnostic arteriography (correlation coefficient 1.00). Initial treatment by
      mechanical or pharmacological means was unsuccessful when performed.
      Superselective transcatheter embolization of the ipsilateral common penile artery
      resolved the priapism in all cases. The interval from onset to resolution of
      priapism was 4 to 126 days. Full erectile function return was delayed from 2
      weeks to 5 months, most likely from resolving clot lysis. Full erection quality
      was restored in 6 of 7 patients with persistent function and restored frequency
      of intercourse at 6 to 67 months. Reestablished cavernous artery flow in
      previously embolized arteries was demonstrated on followup ultrasonography.
      Surgical treatment was not required in any case. We conclude that arterial
      priapism occurs in the absence of neurogenic-mediated relaxation, and is
      sustained by high oxygen tension and shear stress associated with the cavernous
      artery laceration. Embolization therapy offers effective management of the
      pathophysiology with high preservation of premorbid erectile function.

PMID- 8158766
TI  - Impotence.

PMID- 8158767
TI  - Squamous cell carcinoma of the penis. IV. Prognostic factors of survival:
      analysis of tumor, nodes and metastasis classification system.
AB  - Various prognostic factors of survival were assessed in 118 patients with
      squamous cell carcinoma of the penis treated at The Netherlands Cancer Institute
      between 1956 and 1989. Using the clinical parameters of the tumor, nodes and
      metastasis classification system of the International Union Against Cancer (1978
      version) and a differentiation system consisting of 3 grades the prognostic
      relevance for survival was analyzed. T category, N category and grade of
      differentiation showed statistical significance in the univariate analysis.
      Patients with small tumors, clinically negative nodes and well differentiated
      tumors showed a favorable prognosis. Only N category and grade were independent
      prognostic factors of survival using the Cox proportional hazards model. On the
      basis of the survival analysis a stage grouping consisting of 3 stages is
      proposed with 5-year survival probabilities for stages 1, 2 and 3 of 93%, 55% and
      30%, respectively. A revised version of the tumor, nodes and metastasis system
      was introduced in 1987. This latest version was analyzed with the previous
      method, which was used in this report, and prognostically important and
      clinically useful parameters, such as the size of the primary tumor and evidence
      of fixation of the regional lymph nodes, have been discarded. The changes in the
      revised version seem to have little relevance to clinical staging. The revised
      version should be considered a histopathological classification only.

PMID- 8158768
TI  - Carcinoma of the penis.

PMID- 8158769
TI  - Andrological status before and after liver transplantation.
AB  - To determine the impact of liver transplantation on andrological status, we
      compared the endocrine profiles and spermiograms of 2 cohorts of patients before
      (9) and after (11) transplantation. Before liver transplantation testosterone
      (1.1 +/- 0.7 ng/ml) and free testosterone (2.0 +/- 1.6 pg/ml) were pathologically
      decreased in all 9 cases, and luteinizing hormone was lower (1.8 +/- 1.4 mIU/ml)
      in 5. Only 3 of 9 patients were able to produce ejaculates before liver
      transplantation, all of which were azoospermic. After a mean interval of 28 +/- 9
      months (range 4 to 34 months) following liver transplantation testosterone (5.3
      +/- 1.1 ng/ml), free testosterone (15.3 +/- 5.0 pg/ml) and luteinizing hormone
      (6.2 +/- 3.7 mIU/ml.) were consistently within the normal range, with a highly
      statistically significant difference (p < 0.025) from pre-liver transplantation
      values. Semen analyses after liver transplantation revealed normal density,
      motility and normal forms in 5 patients, 2 suffered from
      oligoasthenoteratospermia and 4 were unable to produce an ejaculate for semen
      analyses. These data demonstrate that the hypothalamic-pituitary-testicular
      hormone axis and gonadal tissue are capable of resuming normal function after
      liver transplantation in men with chronic liver failure who suffered from massive
      andrological dysfunction before transplantation.

PMID- 8158770
TI  - Results in the United States with sperm microaspiration retrieval techniques and
      assisted reproductive technologies. The Sperm Microaspiration Retrieval
      Techniques Study Group.
AB  - Improved methods of urological microsurgery and of various assisted reproductive
      technologies have resulted in the ability to achieve pregnancies with sperm
      aspirated microsurgically from men with bilateral congenital absence of the vasa
      deferentia or with ductal obstructions that cannot be surgically reconstructed. A
      survey was conducted of the results of such procedures performed in the United
      States during approximately 2 years. Female partner ovarian stimulation was
      initiated in 219 instances at 22 centers. Of the 219 procedures 23 (11%) were
      terminated without attempting any form of gamete fertilization or insemination of
      the wife for various reasons (no sperm or too few sperm retrieved, poor to absent
      sperm motility or poor quality eggs). The etiology of azoospermia in the 219
      procedures was congenital absence of the vasa deferentia in 115 cases (52%),
      other congenital conditions in 15 (7%), failed vasectomy reversal in 37 (17%),
      infection in 4 (2%), other conditions (mainly ejaculatory dysfunctions that did
      not respond to electroejaculation and complex ductal obstructions) in 26 (12%)
      and not specified in 22 (10%). When only patient sperm was used pregnancy was
      achieved in 12 of 115 wives (10%) of those men who had congenital absence of the
      vasa deferentia and in 0 to 14% of the wives of men whose azoospermia was caused
      by other conditions. Of the 219 menstrual cycles in which ovarian stimulation was
      initiated pregnancy occurred in 24 (11%) with patient sperm and in 9 (4%) with
      donor sperm. Of these 33 pregnancies a full-term, live delivery occurred in 17
      (52%), while 8 (24%) were ongoing at the time of reporting, 2 (6%) miscarried, 3
      (9%) were chemical pregnancies, 1 (3%) resulted in a stillborn child and the
      outcome was unknown in 2 (6%). This new therapy offers only a modest chance of
      pregnancy. However, it affords men with azoospermia the opportunity to achieve
      paternity with their own sperm when other therapies are not available or
      applicable.

PMID- 8158771
TI  - Prevalence of sperm bound antibodies in infertile men with varicocele: the effect
      of varicocele ligation on antibody levels and semen response.
AB  - An increased level of antisperm antibodies has been demonstrated in infertile men
      with varicocele compared with normal fertile men, suggesting a possible cause and
      effect relationship. To evaluate the possible etiological role of antisperm
      antibodies in varicocele patients, we performed a prospective study of 32
      infertile men undergoing varicocele ligation. Semen analyses and antisperm
      antibodies as measured by the immunobead test were performed preoperatively and
      postoperatively at 3 and 6 months. Of the infertile men with varicocele 28% had a
      positive immunobead test compared with 0% of normal fertile men. The average
      total motile sperm count was significantly different (p < 0.05, 2-tailed t test)
      for 9 varicocele patients with sperm-bound antibody (3.2 x 10(6)) compared with
      23 without antibody (8.4 x 10(6)). Postoperatively, 68% of all patients exhibited
      improved semen parameters, with no change in antibody status in either group.
      Among the antibody positive group 71% showed an increase in motile sperm per ml.
      of 2.8 x 10(6) to 17.2 x 10(6) (525% increase, p < 0.05), while in the antibody
      negative group 67% showed an increase of 3.8 x 10(6) to 24.9 x 10(6) (553%
      increase, p < 0.05). Our study suggests that there is an increased incidence of
      sperm-bound immunoglobulin in infertile varicocele patients and an apparent
      adverse effect on semen parameters in these patients. However, the presence of
      sperm-bound immunoglobulin did not affect the percentage response to surgical
      correction, nor can we postulate an immunological mechanism as a major
      etiological factor in varicocele induced infertility.

PMID- 8158772
TI  - Management of testicular masses incidentally discovered by ultrasound.
AB  - Incidental nonpalpable testicular masses were discovered in 9 patients during
      approximately 1,600 scrotal ultrasound examinations done for other indications.
      Of the 9 lesions 7 (78%) were benign (4 Leydig cell tumors, 2 Sertoli cell tumors
      and 1 interstitial fibrosis) and 2 (22%) were malignant (1 teratocarcinoma and 1
      seminoma). Five lesions (55%) were less than 1 cm (4 benign and 1 malignant),
      while 4 (45%) were 1 to 2 cm (3 benign and 1 malignant). Seven lesions (78%) were
      hypoechoic, 1 (11%) was hyperechoic and 1 (11%) was cystic. We conclude that
      incidentally discovered nonpalpable lesions are usually benign. Management should
      include inguinal exploration with frozen section diagnosis. The testis can be
      spared if the lesion is benign. Ultrasound followup should be used only if there
      is a strong clinical suspicion of a nonneoplastic lesion, such as recent trauma
      or infection. It is suggested that nonpalpable tumors discovered in patients with
      metastatic germ cell tumor should be treated as malignant.

PMID- 8158773
TI  - Immunohistochemical determination of p53 protein nuclear accumulation in
      prostatic adenocarcinoma.
AB  - Abnormalities of the TP53 gene are currently the most common genetic alterations
      associated with human malignancy. The study of altered patterns of p53 protein
      expression in primary prostate cancer has to date yielded a much lower incidence
      of alteration compared to bladder, colon, lung and breast cancer. However, the
      analysis of prostate cancer metastases has been limited. The objective of our
      study was to determine the prevalence of p53 nuclear accumulation in primary,
      metastatic and hormone refractory prostatic adenocarcinoma, and to characterize
      its relationship with conventional clinicopathological variables. We used 2
      antibodies (mouse monoclonal PAb 1801 and rabbit polyclonal CM-1) and an
      immunohistochemical method in 93 paraffin embedded tumors (48 primary tumors, 29
      lymph node metastases and 16 bone metastases) to assess p53 nuclear accumulation.
      Overall, p53 nuclear accumulation was observed in 19 tumors (20%), including 17
      with PAb 1801 and CM-1 immunoreactivities, and 2 with CM-1 immunoreactivity only.
      The pattern of p53 immunoreactivity was heterogeneous in most tumors, with only 3
      cases exhibiting homogeneous staining. Primary, lymph node and bone metastases
      exhibited p53 nuclear staining in 9 of 48 (19%), 2 of 29 (7%) and 8 of 16 (50%)
      cases, respectively (p = 0.003). In 6 of 10 primary hormone refractory tumors
      (60%) and in 3 of 38 primary hormone naive tumors (8%) p53 nuclear
      immunoreactivity was expressed (p = 0.002). P53 nuclear accumulation was
      significantly more common in higher grade primary tumors (p = 0.007). Our results
      suggest that p53 nuclear accumulation is relatively uncommon in prostate cancer.
      However, p53 nuclear accumulation appears to be associated with advanced stages
      of disease, as illustrated by its relatively higher occurrence in hormone
      refractory tumors and bone metastases. Furthermore, the significantly greater
      prevalence of p53 accumulation in bone metastases is currently the highest
      reported for prostate cancer.

PMID- 8158774
TI  - Testicular androgens in prostate cancer patients treated with a luteinizing
      hormone releasing hormone agonist.
AB  - Luteinizing hormone releasing hormone agonists have been shown to reduce the
      levels of androgens in the peripheral circulation and to reduce prostate volume.
      The objective of this study was to quantify testicular function in patients with
      metastatic carcinoma of the prostate treated with a luteinizing hormone releasing
      hormone agonist, leuprolide, by analysis of spermatic vein blood for testosterone
      and androstenedione, and by determination of the maximum velocity of the 17 beta
      hydroxysteroid oxidoreductase enzyme in testicular tissue in vitro. A chemical
      analysis of the spermatic vein blood of 19 patients with a median age of 78 years
      revealed the presence of significantly high levels of testosterone and
      androstenedione, 20.7 +/- 1.9 micrograms % and 6.7 +/- 0.7 micrograms %,
      respectively. These androgens could not be detected in patients treated with
      leuprolide before orchiectomy. Patients treated with leuprolide for several
      months followed by a period of no treatment before orchiectomy secreted
      testosterone and androstenedione levels comparable to the control group. The
      maximum velocity of the 17 beta-hydroxysteroid oxidoreductase enzyme in vitro in
      the testes of the leuprolide treated patients was significantly inhibited. Enzyme
      activity returned to normal levels when leuprolide treatment was followed by a
      recovery period of no treatment before orchiectomy.

PMID- 8158775
TI  - Some small prostate cancers are nondiploid by nuclear image analysis: correlation
      of deoxyribonucleic acid ploidy status and pathological features.
AB  - The biological behavior of a prostate cancer can be predicted to some degree by
      the volume and extent (stage) of the tumor, and its histological grade. The
      deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another
      independent prognostic factor for localized prostate cancer. We determined the
      DNA ploidy value of each individual focus of cancer in radical prostatectomy
      specimens using nuclear image analysis (CAS 200 system). Ploidy results were
      correlated with the volume, Gleason grade and zone of origin (transition zone or
      peripheral zone) of each tumor, and with the presence of extracapsular extension
      or seminal vesicle invasion. There were 141 separate cancers in 68 patients (mean
      2.1 per prostate): 9 clinical stage A1, 22 stage A2, 23 stage B1 and 14 stage B2.
      DNA ploidy correlated significantly (p < 0.0001) with volume, grade,
      extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or
      less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to
      0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers
      confined to the prostate 76% were diploid, compared to only 13% of those with
      extraprostatic spread. Most cancers of transition zone origin (86%) were diploid,
      compared to only 49% of peripheral zone cancers, and ploidy and volume
      relationships were significantly different for peripheral zone cancers compared
      to transition zone cancers. All small nondiploid cancers arose in the peripheral
      zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc. We
      conclude that prostate cancers that are nondiploid are highly likely to have
      adverse pathological features. Some small prostate cancers contain a nondiploid
      cell population and these cancers arise predominantly within the peripheral zone
      of the prostate. Ploidy and volume relationships provide further support for the
      hypothesis that there is a difference in malignant potential between cancers of
      peripheral zone and transition zone origin.

PMID- 8158776
TI  - Prostate cancer detection.

PMID- 8158777
TI  - Accuracy of combined computerized tomography and fine needle aspiration cytology
      in lymph node staging of localized prostatic carcinoma.
AB  - The sensitivity and accuracy rate of computerized tomography (CT) in lymph node
      staging of localized prostatic carcinoma is commonly considered to be low. Fine
      needle aspiration cytology of pathological lymph nodes seen on radiological
      staging can enhance this low accuracy rate. We prospectively investigated the
      accuracy of CT and fine needle aspiration cytology in lymph node evaluation of
      285 patients with clinically locally confined prostatic carcinoma. The
      sensitivity, specificity and accuracy rates of this combined method were 77.8%,
      100% and 96.5%, respectively. False-negative staging results were found in only
      10 patients with minimal nodal disease. Although in contrast with previous
      reports, combined CT and fine needle aspiration cytology in our hands seems to be
      a highly efficient staging method for lymph node involvement. This method could
      be considered as an alternative to surgical lymphadenectomy in the preoperative
      evaluation of the nodal status of patients with localized prostatic carcinoma who
      are scheduled for radical prostatectomy or curative radiotherapy.

PMID- 8158778
TI  - Extraperitoneal laparoscopic staging pelvic lymph node dissection.
AB  - As laparoscopic techniques develop, endoscopic lymph node dissection is becoming
      preferred as the minimally invasive technique for lymph node staging of pelvic
      malignancies. We developed an extraperitoneal laparoscopic approach to staging
      pelvic lymphadenectomy, and describe our technique, results and experience in our
      initial 9 patients.

PMID- 8158779
TI  - Techniques for nodal staging in prostate cancer.

PMID- 8158780
TI  - Survival of men with clinically localized prostate cancer detected in the eighth
      decade of life.
AB  - We reviewed our experience with the management of men 70 to 79 years old with
      clinically localized prostate cancer to determine whether surgical candidates
      were likely to die of intercurrent disease soon after the disease was diagnosed.
      Of 101 men in the eighth decade of life who were surgical candidates by all
      criteria other than patient age 44 underwent radical prostatectomy, whereas 57
      were managed by medical therapy including observation, radiation therapy and/or
      androgen deprivation. Five patients died in the surgical group at a median
      followup of 59 months, only 1 of whom died of intercurrent disease. Among 15
      deaths in the medical group metastatic prostate cancer was the most common cause
      and all deaths from prostate cancer occurred more than 3 years after diagnosis.
      Survival for the surgical group was significantly better than that for the
      medical group during followup (p < 0.01 log-rank test). We conclude that men at
      our institution who underwent radical prostatectomy in the eighth decade of life
      did not frequently die of intercurrent disease, and experienced acceptable
      morbidity and mortality rates. We believe that men with localized prostate cancer
      should not be denied a radical operation based on age alone.

PMID- 8158781
TI  - Prostate cancer therapy.

PMID- 8158782
TI  - Genitourinary dysfunction in multiple system atrophy: clinical features and
      treatment in 62 cases.
AB  - Multiple system atrophy is a disorder characterized by progressive neuronal
      atrophy at certain sites of the central nervous system, several of which are
      important in the control of urogenital function. The neuro-urological features of
      62 patients with this condition are described. All patients had abnormal urethral
      or anal sphincter electromyography when individual motor unit analysis was
      performed, a finding diagnostic of the condition in the appropriate clinical
      setting. Impotence occurred in 96% of the men and was the first symptom alone in
      37%. Urinary symptoms resulted from a combination of detrusor hyperreflexia and
      urethral sphincter weakness followed by failure of detrusor contraction. In men
      these symptoms simulated those of outflow obstruction so that 43% underwent
      prostatic or bladder neck surgery before the correct diagnosis was made. Stress
      incontinence occurred in 57% of the women and of these half had undergone
      surgery. The results of surgery in both sexes were poor. Treatment with
      intermittent catheterization, anticholinergic medication and desmopressin spray
      markedly improved continence in 82%. The importance of recognizing this disorder
      and introducing effective, nonoperative treatments is stressed.

PMID- 8158783
TI  - Ileal bladder augmentation combined with ileal ureter replacement in advanced
      urogenital tuberculosis.
AB  - We report a case of active tuberculosis associated with a right nonfunctioning
      kidney and nearly total loss of bladder capacity. Percutaneous nephrostomy and
      right nephroureterectomy were performed while the patient was undergoing triple
      drug therapy. Definitive surgical treatment consisted of ileal bladder
      augmentation and ileal ureter replacement. Normal urodynamics of the upper
      urinary tract and normal voiding with complete return of bladder capacity were
      achieved. Metabolic acidosis was treated successfully by sodium hydrogen
      carbonate.

PMID- 8158784
TI  - Oral conjugated estrogen therapy for treatment of hemorrhagic cystitis.
AB  - We report 7 cases of severe hemorrhagic cystitis that required repeated
      transfusions, surgical intervention and oral conjugated estrogens. Of these 7
      cases hematuria resolved completely in 5 during estrogen therapy and decreased
      sufficiently in 1 to preclude further transfusion. We found conjugated estrogens
      to be an effective, simple, inexpensive, well tolerated and readily available
      treatment for hemorrhagic cystitis.

PMID- 8158785
TI  - Tubercular cavity behind the prostate and bladder: an unusual presentation of
      genitourinary tuberculosis.
AB  - Genitourinary tuberculosis, which is still common in developing countries,
      sometimes has an unusual presentation. We report 2 cases of a tubercular cavity
      behind the bladder and prostate which initially eluded diagnosis, and discuss
      pathogenesis and management of this rare entity.

PMID- 8158786
TI  - Severe reversible neutropenia following treatment of prostate cancer with
      flutamide.
AB  - Flutamide was administered to a patient in conjunction with orchiectomy for stage
      D2 prostate cancer. Subsequently, profound neutropenia developed with a
      neutrophil count of 0.28 x 10(9)/l. Bone marrow aspirate showed granulocyte
      hypoplasia and maturation arrest consistent with drug induced injury. Neutrophil
      count returned to normal after discontinuation of flutamide and administration of
      a short course of granulocyte colony-stimulating factor. Other medications were
      continued with no effect on neutrophil count. The appearance of the bone marrow
      and the return of neutrophils after the discontinuation of flutamide indicate
      that flutamide may have contributed to neutropenia.

PMID- 8158787
TI  - Re: Should the testicular artery be preserved at varicocelectomy?

PMID- 8158788
TI  - Partial nephrectomy in a metachronous multilocular cyst of the kidney (cystic
      nephroma).
AB  - Cystic nephroma, that is multilocular cyst, is an uncommon renal neoplasm once
      thought to occur only unilaterally. We report a rare case of bilateral
      metachronous cystic nephroma in a child, which was treated by partial
      nephrectomy. Because of its benign nature this lesion is best managed by nephron
      sparing surgery. Exploration of the contralateral kidney is not necessary if
      modern radiological techniques are used. Magnetic resonance imaging angiography
      is an excellent noninvasive method to assess renal vessels before partial
      nephrectomy. Periodic ultrasound or computerized tomography screening of the
      remaining renal unit is recommended.

PMID- 8158789
TI  - Complete nonunion of the ureterovesical junction with preservation of renal
      function.
AB  - We report on a neonate with a history of failure to thrive who had a large right
      abdominal mass. Renal ultrasound showed a large cystic mass that arose from the
      upper pole of the hydronephrotic right kidney. Preoperative antegrade pyelography
      confirmed that the mass communicated with 1 kidney. Further evaluation revealed
      no communication of the ureter with the bladder or vagina. Exploratory surgery
      identified the mass and intraoperative pyelography revealed no communication with
      the bladder. After resection of the mass and nephrostomy placement,
      reimplantation of the right ureter demonstrated complete atresia of the distal
      right ureter. Preservation of the remaining renal parenchyma was possible,
      because the functioning lower pole collecting system communicated with the cystic
      mass that arose from the upper pole.

PMID- 8158790
TI  - Cystic lesion of the buttock communicating with the lateral side of the posterior
      urethra.
AB  - We report a case of a congenital cystic lesion of the right buttock without
      cutaneous or rectal fistula. The cystic lesion communicated with the right
      lateral side of the posterior urethra via a fistulous tract.

PMID- 8158791
TI  - The posterior sagittal pararectal approach to posterior urethral anomalies.
AB  - We report a case of enlarged symptomatic utricle that was excised using a
      posterior sagittal pararectal approach. This surgical approach provides direct
      access to the posterior urethra to permit complete resection of the utricle and
      optimal exposure for accurate urethral repair.

PMID- 8158792
TI  - Molecular feminization of mouse seminal vesicle by prenatal exposure to
      diethylstilbestrol: altered expression of messenger RNA.
AB  - Exposure to estrogens during critical stages of development has been reported to
      cause irreversible changes in estrogen target tissues such as the reproductive
      tract. In fact, recent studies using mice describe prenatal estrogen exposure
      resulting in the expression of the major estrogen-inducible uterine secretory
      protein, lactoferrin (LF), by the seminal vesicles of the male offspring. Thus,
      we have studied the role of estrogens in abnormal and normal gene expression in
      the developing male reproductive tract using LF and seminal vesicle secretory
      protein IV (SVS IV), an androgen-regulated murine seminal vesicle secretory
      protein, as markers. Lactoferrin and SVS IV protein and mRNA expression were
      studied in histological samples by using the techniques of in situ hybridization
      (ISH) and immunohistochemistry (IHC). Seminal vesicle secretory protein IV was
      expressed in all (100%) epithelial cells of the control seminal vesicle, but this
      protein was decreased by castration. However, LF expression was undetectable by
      ISH or IHC in control seminal vesicle epithelium. Lactoferrin was inducible in 2%
      of the seminal vesicle epithelial cells from adult castrated mice treated with
      estradiol 17 beta (E2; 20 micrograms/kg/day for 3 days), indicating that a small
      percentage of the seminal vesicle cells could be induced to secrete LF after
      modification of the endocrine environment. Prenatal DES treatment (100
      micrograms./kg. maternal body weight on days 9 through 16 of gestation) resulted
      in the male offspring exhibiting constitutive expression of LF in 5% of the
      seminal vesicle epithelial cells, while expression of the androgen-regulated
      protein SVS IV was slightly decreased. The maximal contrast between LF and SVS IV
      expression was observed in prenatally DES-treated mice that were subsequently
      castrated as adults and further treated with E2; LF was detected in 40% of the
      epithelial cells in these mice. Double immunostaining techniques revealed that
      epithelial cells which were making LF had ceased production of SVS IV. Since a
      large percentage of the epithelial cells in the intact prenatal DES exposed male
      was capable of expressing the normal gene product, SVS IV, it was concluded that
      DES treatment during prenatal development appears to imprint or induce estrogenic
      sensitivity in the adult seminal vesicle, causing increased production of LF. The
      results suggest that this altered protein response may be an example of atypical
      gene expression in male reproductive tract tissues following hormonal
      manipulation early in development.

PMID- 8158793
TI  - Bladder pressure sensors in an animal model.
AB  - Urinary incontinence due to detrusor hyperreflexia might be inhibited on demand
      if changes in bladder pressure could be detected by sensors and transferred into
      pudendal nerve electrostimulation. The aim of this study is to investigate how
      the bladder wall reacts on different sensor implants. Sensors were implanted in
      twelve goats. In group 1 (n = 8) real sensors were placed on the peritoneal
      surface of the bladder dome, between the peritoneum and the muscular layer, and
      between the cervix and bladder. In group 2 (n = 4), dummy sensors were placed
      between the mucosal and muscular layers. During follow-up as long as 25 months,
      urodynamic studies, radiographic control and urine cultures were done. In group
      1, sensors placed between the peritoneum and muscular layer gave the best
      results. In group 2, 11 of the 12 sensors eroded. The authors conclude that
      implantation of sensors in the bladder wall is feasible.

PMID- 8158794
TI  - Developmental changes in normal fetal bovine whole bladder physiology.
AB  - In the present study, normal and experimentally altered whole fetal bovine
      bladders have been used in vitro to study developmental changes in compliance and
      capacity. For the first time, we have attempted to define the relative
      contributions of the detrusor and mucosal layers to bladder compliance. Fetal
      bovine bladder compliance increases with fetal development. Elimination of the
      active component of smooth muscle tension improves compliance and increases
      capacity more than 60% in younger fetuses but only 35% in older fetuses. Active
      smooth muscle tension as evaluated by whole bladder cystometry is highest in the
      youngest fetuses and decreases with fetal age. Surgical removal of the detrusor
      layer (smooth muscle and connective tissue) also increases compliance and
      capacity substantially in all fetal bladders. These observations show that both
      smooth muscle and connective tissue are important in the function of the
      developing fetal bladder. Changes in both of these bladder wall components
      probably occur during development and are responsible for the physiologic changes
      observed.

PMID- 8158795
TI  - Inhibitory effect of minocycline on in vitro invasion and experimental metastasis
      of mouse renal adenocarcinoma.
AB  - Degradation of the extracellular matrix by metalloproteinases is a critical
      phenomenon in cancer invasion and metastasis. Recent studies have revealed that
      minocycline (minocycline hydrochloride, a tetracycline) suppresses in vivo and in
      vitro mammalian collagenolytic activity. We investigated whether minocycline
      inhibited in vitro invasion and experimental pulmonary metastasis in subline-2 of
      streptozotocin-induced mouse renal adenocarcinoma (MRAC-PM2) cells. In vitro
      invasion assay demonstrated that treatment with 0.5 microgram/ml or 5.0
      micrograms/ml minocycline significantly inhibited the invasion of MRAC-PM2 cells.
      In addition, intraperitoneal administration of 0.5 mg per mouse minocycline
      reduced the number of metastatic nodules in the lung when MRAC-PM2 cells were
      injected intravenously. Minocycline also suppressed type IV collagenolytic
      activity of the cells. However, the drug did not affect [3H]-thymidine uptake,
      growth of subcutaneously inoculated cells, attachment to the extracellular
      matrices, or haptotactic migration of the cells. These results indicated that the
      inhibitory action of type IV collagen degradation by minocycline can contribute,
      in part, to suppression of the in vitro invasion and metastatic potential of MRAC
      PM2 cells.

PMID- 8158797
TI  - In vivo laser light distribution in human prostatic carcinoma.
AB  - The extent of laser light diffusion within prostatic tumor is of major importance
      in the treatment of localized prostatic cancer with photodynamic therapy (PDT).
      The penetration of 633 nm. wavelength red light was studied in eleven patients
      with suspected prostatic cancer using a novel method suitable for in situ
      measurements. Light delivery and detector fiber, placed interstitially within the
      gland, determined light attenuation at different interfiber separations. Of 11
      patients, 10 had bilateral and 1 had single lobe studies. The mean +/- the
      standard error of the mean attenuation coefficients (sigma eff) for benign and
      malignant prostate tissue were 0.35 +/- 0.02 mm-1 and 0.36 +/- 0.02 mm-1,
      respectively, indicating similar optical densities (p = .58). Patients with
      bilateral lobe involvement showed little intraglandular variation in sigma eff (p
      = 0.23). However, there was interpatient variation (sigma eff = 0.28 to 0.48 mm
      1) reflecting biological differences which, though therapeutically important,
      were not statistically significant (p = 0.057). This study showed that treatment
      requires individualization and predicted that 4 cylindrical diffusers are
      expected to destroy 25 ml. of prostatic tumor with PDT.

PMID- 8158796
TI  - Contractility parameters of the guinea pig bladder in situ: similarity to human
      bladder contractility.
AB  - The parameters P(isv) (active isovolumetric detrusor pressure) and Vmax (maximum
      shortening velocity), which characterize the contractility of the detrusor
      muscle, were determined in guinea pigs. To this end it was necessary to develop a
      method of measuring flow rates in these small animals. The values found were used
      to calculate the contractility parameter Wmax. Thirteen animals were used. The
      results found for P(isv) and Vmax were 43.0 +/- 3.7 cm. H2O and 20.2 +/- 3.7 mm.
      per second, respectively. The latter corresponded to about 0.38 muscle lengths
      per second, which is similar to values reported for bladder strips from other
      species. Previous work showed that in vitro P(isv) decreased with increasing
      bladder volume over a wide range of volumes. In vivo P(isv) seemed to be
      independent of bladder volume. This suggests that neurogenic stimulation
      intensifies as volume increases. Vmax also was independent of volume. Wmax
      appeared to be suitable for detecting differences in the contractility of the
      bladders of different animals. Values were not significantly different in
      isovolumetric and nonisovolumetric contractions. Normalized to the size of the
      bladder, the Wmax values indicated that the power generated by the guinea pig
      bladder is similar to the power generated by the human bladder.

PMID- 8158798
TI  - A new triple-balloon, four-channel vascular catheter for use in renal
      transplantation.
AB  - While current surgical techniques of renal transplantation afford excellent
      results, some steps of the operation are associated with potential morbidity.
      Application of vascular clamps on an atherosclerotic recipient artery can cause
      plaque fracture or atheroembolism. atheroembolism. Prolonged revascularization
      time may aggravate ischemic allograft damage. Based on the premise that arterial
      occlusion by an intraluminal balloon is less damaging to the vascular endothelium
      than an external vascular clamp, a new three-balloon, four-channel vascular
      catheter has been developed for use in renal transplantation. Catheters are
      inserted by the Seldinger technique, one catheter being positioned in each
      recipient external iliac artery and external iliac vein. Vascular control of the
      recipient vessels is obtained by inflation of the balloons. A pilot study in four
      dogs has confirmed the technical feasibility of using this catheter during renal
      transplantation. A description of the catheter, technique of surgical placement,
      advantages and potential uses is presented.

PMID- 8158799
TI  - Enhanced antitumor effect of Bacillus Calmette-Guerin in combination with
      fibrinogen on urinary bladder tumor.
AB  - Although intravesical instillation of Bacillus Calmette-Guerin (BCG) is an
      established and effective therapy for superficial urinary bladder tumor (UBT),
      the current major problems are BCG-resistant UBT and recurrence after BCG
      therapy. The injection of BCG and fibrinogen could be expected to induce the
      formation of a fibrin mesh, which would trap BCG and and prolong its antitumor
      action. The present study has been designed to investigate whether fibrinogen has
      the ability to augment antitumor activity of BCG against UBT. A single injection
      of BCG/fibrinogen solution into the subcutaneous tissue of C3H/He mice was
      performed. Histopathological examination revealed prolonged accumulation of BCG
      and marked infiltration of inflammatory cells at the injected site, as compared
      with the injection of BCG or fibrinogen alone. When BCG was used in combination
      with gelatin sponge, prolonged BCG accumulation was also observed, but not many
      inflammatory cells were induced, as compared with injection of BCG/fibrinogen
      combination. When BCG/fibrinogen solution was injected into MBT-2 murine UBT
      transplanted into C3H/He mice, the formation of fibrin fibers, which trap BCG,
      was induced, and many inflammatory cells around the tumor were seen. A pronounced
      inhibitory effect on tumor growth and prolonged survival of tumor-bearing mice
      were achieved, as compared with the injection of BCG alone. Dead BCG/fibrinogen
      solution had a modest inhibitory effect on the tumor growth. This study suggests
      that combination treatment with BCG and exogenous fibrinogen may prolong
      accumulation of BCG by BCG by trapping BCG in fibrin meshwork, and may induce
      marked infiltration of inflammatory cells into tumor stroma, causing marked
      regression of the tumor. The possible clinical implications of the combined use
      of BCG and fibrinogen are discussed.

PMID- 8158800
TI  - Ductal budding and branching patterns in the developing prostate.
AB  - Development of the prostate was studied by serial section reconstruction and
      computer-assisted three-dimensional analysis. A comparison of ductal budding in
      species of rat and mouse and the human revealed patterns consistent with common
      developmental characteristics. Ventral, lateral and dorsal lines of epithelial
      buds, which emanated from the urogenital sinus into the surrounding periurethral
      mesenchyme, followed ventro-dorsal and cranio-caudal axes. Subsequent branching
      morphogenesis was associated with specific mesenchymal condensations. These
      patterns of budding were closely related to the adult lobe architecture in the
      rodent prostate. In the human fetus, prostate ductal budding exhibited patterns
      compatible with the current concept of zonal anatomy.

PMID- 8158801
TI  - Population-based medicine merges clinical care, epidemiologic techniques.

PMID- 8158802
TI  - Updated guidelines address "hot topics".

PMID- 8158803
TI  - Restenosis trials suggest role for remodeling.

PMID- 8158804
TI  - Consensus panel says benefits of screening women for ovarian cancer currently
      unproven.

PMID- 8158805
TI  - From the Institute of Medicine.

PMID- 8158806
TI  - From the Centers for Disease Control and Prevention. Daily dietary fat and total
      food-energy intakes--NHANES III, Phase 1, 1988-91.

PMID- 8158807
TI  - From the Centers for Disease Control and Prevention. Health-risk behaviors among
      persons aged 12-21 years--United States, 1992.

PMID- 8158808
TI  - From the Centers for Disease Control and Prevention. Human plague--United States,
      1993-1994.

PMID- 8158809
TI  - Alzheimer's disease, apolipoprotein E4, and gender.

PMID- 8158810
TI  - Evaluating behavioral interventions: need for randomized controlled trials.

PMID- 8158811
TI  - Accuracy of precordial percussion and palpation.

PMID- 8158812
TI  - Immunoaugmentative therapy.

PMID- 8158813
TI  - Immunoaugmentative therapy.

PMID- 8158814
TI  - Body weight and mortality.

PMID- 8158815
TI  - Increasing oxygen delivery in surgical patients.

PMID- 8158816
TI  - The effect of parental history of myopia on children's eye size.
AB  - OBJECTIVE: To evaluate whether eye size and shape are different in children based
      on their parental history of myopia. DESIGN: A community-based cohort study of
      schoolchildren (aged 6 to 14 years), the Orinda (Calif) Longitudinal Study of
      Myopia. SETTING: Four campuses of the Orinda Union School District, a
      predominantly white, high socioeconomic status community. PARTICIPANTS: A cross
      sectional volunteer sample of 716 children (662 non-myopic) in the first, third,
      and sixth grades in 1989, 1990, and 1991. All children in those grades were
      eligible for inclusion in the study. INTERVENTION(S): None. MAIN OUTCOME
      MEASURES: Refractive error (measured by autorefraction), corneal curvature
      (measured by photokeratoscopy), crystalline lens power (measured by video
      phakometry), and axial ocular dimensions (measured by ultrasonography). RESULTS:
      With prevalent cases of myopia excluded and grade in school and "near work"
      controlled for, children with two myopic parents had longer eyes and less
      hyperopic refractive error (analysis of covariance, P < or = .01) than children
      with only one myopic parent or no myopic parents. A model incorporating parental
      history is only improved by the addition of near work for the prediction of
      refractive error. CONCLUSIONS: Even before the onset of juvenile myopia, children
      of myopic parents have longer eyes. These results suggest that the premyopic eye
      in children with a family history of myopia already resembles the elongated eye
      present in myopia.

PMID- 8158817
TI  - Protection against hepatitis A by an inactivated vaccine.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a new inactivated hepatitis A
      vaccine. DESIGN: Double-blind randomized controlled trial stratified by
      community. SETTING: Community-based in Thailand. STUDY PARTICIPANTS: A total of
      40,119 children, aged 1 to 16 years, attending 148 primary schools: 38,157 (95%)
      entered surveillance a mean of 138 days after receiving vaccine dose 1; 33,586
      (84%) completed the controlled trial of 532 days; and 31,075 (81%) received
      crossover vaccine and remained under surveillance until day 844. INTERVENTION:
      Participants received hepatitis A vaccine or control hepatitis B vaccine starting
      January 7, 1991 (doses in months 0, 1, and 12), and crossed over to the alternate
      vaccine 18 months later. MAIN OUTCOME MEASURE: Cases of hepatitis A (symptoms,
      alanine aminotransferase levels of 45 U/L or higher, and IgM to hepatitis A
      virus) were identified by evaluating school absences of 2 or more days. RESULTS:
      There were no serious adverse reactions despite administration of more than
      109,000 doses of hepatitis A vaccine. Among initially seronegative recipients of
      two doses of hepatitis A vaccine, the proportion with 20 mIU/mL or more of
      antibody to hepatitis A virus before and 5 months after a 1-year booster was 94%
      and 99%, respectively. Of 6976 episodes of illness during the controlled trial,
      there were 40 cases of hepatitis A; 38 were in the control group. Of the 40
      cases, six, all in controls, occurred after the 1-year booster dose. Following
      two doses of hepatitis A vaccine (days 138 through 386), protective efficacy was
      94% (95% confidence interval, 79% to 99%); cumulative efficacy including the
      postbooster period (days 138 to 532) was 95% (95% confidence interval, 82% to
      99%). The two hepatitis A vaccine recipients who had symptomatic infections (257
      and 267 days after dose 1) appeared to have been partially protected since their
      illnesses were brief and associated with only slight increases in alanine
      aminotransferase. CONCLUSIONS: Inactivated hepatitis A vaccine is safe; when
      administered in two doses, it protects against hepatitis A for at least 1 year.

PMID- 8158818
TI  - Recurrent cardiac events in survivors of ventricular fibrillation or tachycardia.
      Implications for driving restrictions.
AB  - OBJECTIVE: To determine when survivors of ventricular tachycardia (VT) or
      ventricular fibrillation (VF) might most safely return to driving. DESIGN:
      Consecutive case series of 501 VT and VF survivors discharged alive between
      August 1978 and October 1989 and followed from 0 to 117 months (mean, 26 months).
      SETTING: Cardiac arrhythmia service of a university hospital. PATIENTS: The study
      group comprised 290 consecutive patients with sustained VT and 211 patients with
      VF who underwent electrophysiological studies and were discharged alive (78%
      male; mean age, 59 years). The mean ejection fraction (available in 338 patients)
      was 0.42. INTERVENTIONS: Antiarrhythmic drug testing for all patients was guided
      by serial electrophysiological testing. Overall, 227 patients (45%) were
      discharged on conventional antiarrhythmic agents, 115 (23%) on amiodarone, 39
      (8%) received an implantable defibrillator, and 120 (24%) received no specific
      antiarrhythmic therapy. MAIN OUTCOME MEASURES: Main outcomes included any event
      that could hamper a patient's ability to operate a motor vehicle. Specifically,
      these events included recurrent VF, poorly tolerated, hemodynamically unstable
      VT, syncope, sudden cardiac death, and implantable defibrillator discharge.
      RESULTS: Event risks were assessed during the first year after hospital discharge
      because that is when most patients decide whether to begin driving again. The 1
      year outcome event rate for all 501 patients was 17%. Three distinct periods of
      risk were identified. The monthly hazard rate was highest in the first month
      after hospital discharge (4.22% per month), intermediate in months 2 through 7
      (1.81% per month), and lowest in months 8 through 12 (0.63% per month). The 191
      patients for whom no successful conventional antiarrhythmic drug could be found
      during electrophysiological testing experienced a persistently high monthly event
      risk (1.6%) during months 8 through 12. CONCLUSIONS: All survivors of VT or VF
      should refrain from driving during the first month after hospital discharge when
      the hazard for events that could impair their ability to drive is greatest. Our
      data would support restricting driving for most patients until the eighth month
      after hospital discharge, when risk becomes lowest. Restriction might be
      lengthened in patients for whom electrophysiological testing finds no
      satisfactory conventional antiarrhythmic agent because their risk remains higher
      than average even after 7 months. Individualized recommendations should be
      allowed because the accident rate for patients who actually suffer sudden death
      is low.

PMID- 8158819
TI  - Relation of the content of prenatal care to the risk of low birth weight.
      Maternal reports of health behavior advice and initial prenatal care procedures.
AB  - OBJECTIVE: Numerous studies have found a relationship between the quantity of
      prenatal care received and birth outcomes. Few studies have had the opportunity
      to examine the content of prenatal care. This study examined the relationship
      between two components of the content of prenatal care: maternal reports of
      health behavior advice received and initial prenatal care procedures performed
      during the first two visits and low birth weight in a national sample of women.
      Advice and initial procedures were categorized based on the recommendations of
      the US Public Health Service Expert Panel on the Content of Prenatal Care.
      DESIGN: Interview survey of a nationally representative sample of women who had
      live births in 1988. PARTICIPANTS: A total of 9394 women, with data from the
      National Maternal and Infant Health Survey. MAIN OUTCOME MEASURE: Low birth
      weight (< 2500 g) as reported on the birth certificate. RESULTS: After
      controlling for other sociodemographic, utilization, medical, and behavioral
      factors, women who reported not receiving all the types of advice recommended by
      the Expert Panel on the Content of Prenatal Care were more likely to have a low
      birth-weight infant compared with women who reported receiving the optimal level
      of advice (odds ratio = 1.38; 95% confidence interval, 1.18 to 1.60). There were
      no differences between women who reported receiving all the recommended initial
      prenatal care procedures and those who reported not receiving all recommended
      prenatal care (odds ratio = 1.00; 95% confidence interval, 0.87 to 1.14).
      CONCLUSION: These data suggest that women who report receiving sufficient health
      behavior advice as part of their prenatal care are at lower risk of delivering a
      low-birth-weight infant.

PMID- 8158820
TI  - Screening for pediatric lead poisoning. Comparability of simultaneously drawn
      capillary and venous blood samples.
AB  - OBJECTIVE: To determine the ability of capillary blood lead levels to accurately
      reflect true blood lead levels in children at risk for lead poisoning. DESIGN: A
      correlation study in which lead levels of capillary blood specimens obtained by
      four different methods were compared with lead levels of simultaneously drawn
      venous blood specimens. SETTING: A central-city pediatric primary care clinic and
      door-to-door home visits in one central-city neighborhood. PATIENTS: Two hundred
      ninety-five children at high risk for lead poisoning aged 6 months to 6 years.
      MAIN OUTCOME MEASURES: Blood lead levels of simultaneously drawn capillary and
      venous blood specimens. RESULTS: Lead levels of all four capillary sampling
      methods were highly correlated (correlation coefficient > or = 0.96) with matched
      venous blood lead levels, with mean capillary-venous differences less than 0.05
      mumol/L (1 microgram/dL). CONCLUSIONS: Capillary sampling is an acceptable
      alternative to venipuncture for lead-poisoning screening in young children.

PMID- 8158821
TI  - Patient outcomes following tricompartmental total knee replacement. A meta
      analysis.
AB  - OBJECTIVE: To provide estimates of patient outcomes following tricompartmental
      knee replacement and to examine variation in outcomes due to patient and
      prosthesis characteristics. DATA SOURCES: English-language articles identified
      through a computerized literature search and bibliography review. STUDY
      SELECTION: Studies were included if they enrolled 10 or more patients at the time
      of initial knee replacement and measured patient outcomes using a global knee
      rating scale. DATA EXTRACTION: Each study was subjected to a blinded qualitative
      assessment and unblinded abstraction of patient characteristics, surgical
      techniques, and outcomes. DATA SYNTHESIS: A total of 130 studies reporting
      patient outcomes on 154 cohorts satisfied inclusion criteria. The total number of
      enrolled patients was 9879 with a mean enrollment of 64.1 patients. The mean
      follow-up was 4.1 years. The mean patient age was 65.0 years, 71.7% of patients
      were women, 62.6% had osteoarthritis, and 26.6% underwent bilateral knee
      replacement. Global rating scale scores improved by 100% for the typical enrolled
      patient, and 89.3% of patients reported good or excellent outcomes. Anatomic
      classification of the prosthesis, percentage of enrolled patients with
      osteoarthritis, publication year, and number of enrolled patients explained 27%
      of the variation in reported mean postoperative global rating scale scores. The
      weighted mean complication rate was 18.1%, and the mean mortality rate per year
      of follow-up was 1.5%. The overall rate of revision during 4.1 years was 3.8%.
      CONCLUSIONS: Tricompartmental knee replacement was a safe and effective procedure
      for the patients reported in these studies. The knee pathology and the type of
      prosthesis were significant predictors of outcomes. Limitations in the reporting
      style of these articles severely constrain the ability to explore variation in
      outcomes due to study, patient, or prosthesis characteristics and restrict their
      generalizability.

PMID- 8158822
TI  - Withdrawing care. Experience in a medical intensive care unit.
AB  - OBJECTIVE: To describe the process and outcomes of withdrawing life-sustaining
      interventions in a medical intensive care unit (MICU). DESIGN: Retrospective case
      series. SETTING: Medical intensive care unit in a community teaching hospital.
      PATIENTS: Consecutive series of 28 patients in whom mechanical ventilation,
      dialysis, and/or vasopressors were withdrawn. We distinguished physiological,
      neurological, and functional rationales for care withdrawal. MAIN OUTCOME
      MEASURES: Duration of discussions, MICU length of stay, and hospital survival.
      RESULTS: Mean +/- SD Acute Physiology and Chronic Health Evaluation (APACHE II)
      score was 27.1 +/- 7.3 on MICU admission, and average +/- SD predicted hospital
      mortality was 61% +/- 22%. Discussions leading to withdrawal of care occurred
      over an average +/- SD of 5.2 +/- 5.5 days, with decisions achieved soonest in
      cases with poor neurological prognosis. Average +/- SD MICU length of stay was
      1.4 +/- 1.8 days following a decision to withdraw MICU care, and only four
      patients received more than 48 hours of additional MICU care. Four patients were
      discharged alive from the hospital. CONCLUSIONS: Patients and their surrogates
      willingly considered outcomes in addition to mortality when considering
      withdrawal of life-sustaining interventions. Finding an accommodation between
      physician judgments and patient preferences took time and effort but was an
      effective means of limiting ineffective life-sustaining efforts. Withdrawing
      futile or unwanted care was not always fatal.

PMID- 8158823
TI  - A new focus on myopia.

PMID- 8158824
TI  - Inactivated hepatitis A vaccines.

PMID- 8158825
TI  - A piece of my mind. The smell of gardenias.

PMID- 8158826
TI  - An overview of health system reform.

PMID- 8158827
TI  - The numerology of graduate medical education reform.

PMID- 8158828
TI  - Myths and realities surrounding health reform.

PMID- 8158829
TI  - Medicaid: lessons from a sleeper program.

PMID- 8158830
TI  - Myocardial perfusion imaging.

PMID- 8158831
TI  - Bacteriuria and pregnancy outcome: a prospective hospital-based study in
      Pakistani women.
AB  - The prevalence of bacteriuria in Pakistani women and its association with
      complications of pregnancy was studied. Out of 1579 women, 77 had bacteriuria
      (4.8%). There was no association of age, gravidity, parity, haemoglobin, pre
      eclampsia, mode of delivery, gestational age at delivery, preterm delivery and
      low birth-weight with presence of bacteriuria. With detection and treatment the
      pregnancy outcome of women with bacteriuria in pregnancy was the same as that of
      those without.

PMID- 8158832
TI  - An assessment of corn oil as a vehicle for cyclosporin A (CsA) at varied
      injection sites in preventing rejection of rat laryngeal allografts.
AB  - This study was designed to determine the efficacy of corn oil as an alternative
      vehicle to olive oil for emulsifying cyclosporin (CsA) in preventing rejection of
      transplanted rat larynges. The issue of varied site absorption was also
      addressed. Thirty animals were transplanted to get 5 viable transplants at two
      weeks for three varied sites of administration; intramuscular (IM), subcutaneous
      (SQ) and intraperitoneal (IP). Five mg/kg of CsA in corn oil was the dose
      administered based on earlier data generated in our laboratory. Postulating
      selective absorption, the indirect measure of laryngeal histopathology, i.e.
      rejection, was chosen over blood levels for evaluation. In the IM group 2 grafts
      evidenced mild rejection whereas 3 showed marked cellular and vascular rejection.
      The SQ group had 1 mild, 1 moderate and 3 with severe rejections. The IP group
      had one moderate rejection and 4 severe rejections. Qualitatively the IM and SQ
      groups were similar. The IP group histologically evidenced far greater cellular
      rejection. CsA 5mg/kg emulsified in corn oil did not differ substantively in
      histologic scope or pattern of rejection from CsA in olive oil in experimental
      rat laryngeal transplantation. Further, the data did not support a change in the
      administration of CsA from an intramuscular site.

PMID- 8158833
TI  - BCG scar survey in Karachi schools.

PMID- 8158834
TI  - Torsion of pelvic organs in a 10-year old girl.

PMID- 8158835
TI  - Thallium-201: an agent for myocardial perfusion and viability imaging.

PMID- 8158836
TI  - Practical epidemiology and biostatistics in research. IV. Putting research into
      operation.

PMID- 8158837
TI  - Use of Norplant in Pakistan: two years experience.
AB  - The acceptability and efficacy of norplant (levonorgestrel sub- dermal implants)
      was assessed over a period of two years among 445 married women aged 19 to 45
      years. Twenty women were lost to follow-up while the remaining 425 were regularly
      followed-up. At the end of two years, 388 women were still continuing with
      norplant (91.2%). During this period, there was only one pregnancy (0.26%). There
      was no significant change in mean systolic or diastolic blood pressure. However,
      there was a significant increase (P < 0.001) in mean weight and decrease (P <
      0.001) in the mean duration of menstrual cycle. Thirty-seven women (8.7%) got the
      implant removed. The major reason for removal (67.6%) was menstrual disturbances.
      Nine acceptors (18.59%) developed side effects, which were related to the type of
      symptoms often associated with steroid contraception. These findings are similar
      to those reported from other countries. The high efficacy (99.74%) and
      acceptability (continuation rate of 91.29%) as well as long acting (5 years)
      nature of norplant suggest that this method of contraception can safely be
      promoted in Pakistan.

PMID- 8158838
TI  - A view of HIV-I infection in Karachi.
AB  - A prospective study on the prevalence of HIV-I infection in Karachi, Pakistan was
      conducted over a period of six years (1986-1992). Over 15,000 individual samples
      and more than 32,000 donor units of individuals residing in Karachi at the time
      of sample collection were tested for HIV-I infection by our screening test EIA
      which revealed a positivity rate of 0.23% and 0.003% in individual and donor
      units respectively by Western Blot. We divided patients into four groups A, B, C
      and D based on the most plausible cause of transmission. The largest number of
      positive patients belonged to group B, who were of either foreign origin or
      expatriates or Pakistanis settled abroad. They comprised approximately 67% of the
      total positive cases and were subjected to testing on strong clinical grounds. In
      individuals of other groups like group A and D, there was history of travel
      abroad from time to time. The only positive donor unit (group C) belonged to a
      person who had been living in Middle East for the last 10-12 years. The last
      group D comprised of samples that were directly sent to us without complete
      history, except for the fact that they had been travelling back and forth. The
      large majority of patients fell in 20-50 years age group. Despite the limitations
      of this study, we conclude that the prevalence of HIV is steadily increasing in
      our population and so far, we have not been able to find an indigenous case of
      AIDS in our series.

PMID- 8158839
TI  - [Leukocyte adhesion deficiency: its clinical and molecular analyses].
AB  - Leucocyte adhesion deficiency is an immunodeficiency disease of autosomal
      recessive inheritance characterized by recurrent bacterial skin infections,
      impired pus formation and delayed wound healing. Leukocytes, including
      granulocytes and lymphocytes, from the LAD show defect in adhesion molecules of
      beta 2 integrin, LFA-1, Mac-1 and p150, 95, on its leukocyte membrane surface.
      This paper is a review article describing clinical features, leukocyte functions
      and molecular basis for the defective expression of the beta 2 integrin molecules
      in the LAD.

PMID- 8158840
TI  - [The role of monocytes in network mediated by both fibronectin and monokines in
      inflammation].
AB  - The effects of both fibronectin (FN) and monokines (IL-1 alpha, IL-6, TNF) on
      monocyte activation were studied. FN in the culture medium (200 micrograms/ml)
      induced strong monokine production that was mediated by the domain epitope
      including RGD sequence on FN and the VLA-5 integrins on monocytes. Each monokine
      or the combination of suboptimal dose of any monokines strongly induced FN
      production. These results indicate that monocytes activation in vitro may depend
      on not only monokines but on adhesion molecules such as FN-VLA-5. Peripheral
      blood monocytes from patients with systemic lupus erythematosus (SLE)
      demonstrated low responses to both fibronectin and monokines, while the plasma
      levels of FN in SLE patients elevated markedly compared with normal individuals
      (640 vs 285 micrograms/ml). Many studies have been reported that cytokines
      elevated in serum from SLE patients. These results indicated that maximally
      activated monocytes with both monokines and soluble FN in vivo in SLE patients
      could not be activated in vitro. Together with these results, FN play important
      roles in the cellular and humoral mechanisms of inflammation.

PMID- 8158841
TI  - [Regulation of the endothelial function by thrombomodulin and/or thrombin
      receptor].
AB  - Thrombin, the final product of blood coagulation cascade, shows several effect on
      the vessel-wall cells. However the effects may be regulated by several thrombin
      receptors on the endothelium. They include thrombomodulin (TM), protease-Nexin,
      heparin-like molecule-antithrombin III complex. These binding sites do not
      transduce the signal of thrombin. Especially TM converts thrombin from a
      procoagulant protease to an anticoagulant. Recently new thrombin receptor was
      identified on the endothelium and platelets. Through this receptor, thrombin
      induces activations both on platelet end-endothelium. In brief platelets
      aggregate and release several factors including serotonin, PDGF, platelet
      factor4, beta-thromboglobulin on the stimulation by thrombin. The endothelium
      release t-PA inhibitor; PAI-1, prostacyclin and endothelin. Thus the activations
      of these cells by thrombin is a key events in hemostasis, wound healing,
      inflammation, atherosclerosis and restenosis of coronary artery after PTCA.

PMID- 8158842
TI  - [Diagnosis and treatment of acute undifferentiated leukemia and AML-MO].
AB  - To characterize AML-MO (MO) and acute undifferentiated leukemia (AUL) clinically,
      questionnaires were sent to nationwide hematology departments in May and August
      1993. From 65 institutions, 71 MO cases (2.2% of acute leukemias, 3% of AML) and
      19 AUL cases (0.4% of acute leukemias) were registered. Median age was 55 (15-81)
      years for MO and 38.5 (15-71) years for AUL, and the M/F sex ratio was 44:27 for
      MO and 19:2 for AUL. Of 48 cases examined for chromosome analysis, 24 (50%) were
      abnormal karyotypes. Of 15 cases examined for electron microscopic
      myeloperoxidase (MPO), 10 (67%) were positive, and of 9 cases examined for
      cytoplasmic antigen by anti-MPO antibody, 7 (78%), were positive. Examination of
      TdT, surface antigen of CD7 and CD34 were performed in 22, 61 and 43 cases and
      each positivity was 59, 51 and 86%, respectively. 3 of 18 cases showed
      rearrangement of immunoglobulin heavy chain gene and 2 of 13 cases showed
      rearrangement of T cell receptor beta gene. With the first-line induction
      chemotherapy, complete remission (CR) was obtained in 34 of 67 MO cases and in 7
      of 18 AUL cases. Median CR duration and median survival for MO cases were 361 and
      387 days and those for AUL were 541 and 578 days, respectively. The remission
      rates were 61% for 54 cases treated with AML chemotherapy regimens and 38% for 13
      cases treated with ALL chemotherapy regimens. 9 cases of MO and AUL who received
      bone marrow transplantation (BMT) had excellently good prognosis compared with
      non-BMT group.

PMID- 8158843
TI  - [Characteristic clinical features and treatment of acute myelocytic leukemia with
      8;21 translocation].
AB  - From 1981 to 1992 forty acute myelocytic leukemia patients with the 8;21
      translocation [t (8;21) AML] were treated with intensive chemotherapy and
      radiotherapy. Their ages ranged from 12 to 81 years at the time of diagnosis. The
      8;21 translocation occurred in 13.8% of all patients with AML. Of the 40 t (8;21)
      AML patients, 10 (25.0%) developed extramedullary tumors at sites such as
      mastoid, orbit and temporal region. This occurred more commonly among younger
      patients. Thirty-eight of the 40 patients (95.0%) achieved complete remission
      (CR). Of these 38 patients, 36 received post-remission chemotherapy. Since 1984,
      29 consecutive patients have been given cranial irradiation, 24Gy, for
      prophylaxis and treatment of leukemic tumors. The twelve years remission and
      survival rate for this group are 68.3% and 62.1%, respectively. Of the 38
      patients achieving CR, in those over 30 years of age at the time of diagnosis, 19
      of 23 remain in first remission, whereas in the younger patients 5 of 13 have
      relapsed. The duration of CR of patients who developed extramedullary tumors was
      shorter than that of patients without such tumors. A second CR was achieved in 7
      of 9 recurrent cases. Three remain in remission 21, 45, and 117 months after
      chemotherapy and allogeneic bone marrow transplantation. We attribute the very
      long duration of CR in our patients with t (8;21) AML to the intensive post
      remission therapy. Younger patients with t (8;21) AML and/or extramedullary
      tumors probably should receive early bone marrow transplantation.

PMID- 8158844
TI  - [New strategy for diagnosis and treatment of acute promyelocytic leukemia with t
      (15;17)].
AB  - All-trans retinoic acid (ATRA)-therapy against acute promyelocytic leukemia (APL)
      is epoch-making in the sense of the first success in both tumor-differentiation
      therapy and molecule-targeted therapy. Kouseishou APL-study group performed three
      clinical studies to refractory APL with ATRA from 1990 to 1993. Complete
      remission (CR) was obtained in 82%, 88% and 78% of 22, 41 and 46 patients,
      respectively. Molecular diagnosis of the t (15;17) translocation was possible
      using Southern blot analysis and reverse transcriptase polymerase chain reaction
      (RT-PCR).

PMID- 8158845
TI  - [Effects of 9-cis retinoic acid on hematopoiesis in vitro].
AB  - 9-cis retinoic acid (cRA) is a high affinity ligand for RXR and binds efficiently
      to RAR. cRA in general was more potent than all-trans RA (tRA) in suppressing
      clonal growth and inducing differentiation of HL-60 and human leukemic cells. At
      very low concentrations, retinoid stimulate proliferation of leukemic cells
      rather than induce their differentiation. Also, cRA in combination with tRA could
      induce differentiation of RA resistant HL-60 cells. Steady-state levels of RAR
      alpha mRNA in HL-60 cells were not affected by either cRA or tRA. In contrast,
      cRA, but not tRA could reduced RXR-alpha mRNA accumulation in dose-dependent
      manner. The loss of partner for RAR may result in differential gene regulation
      through the retinoid pathway. These differences in regulation of RAR and RXR mRNA
      might be of physiological significance.

PMID- 8158846
TI  - [Molecular diagnosis and therapeutic strategy for Philadelphia chromosome
      positive acute leukemia].
AB  - We focused on biological characteristics of Philadelphia chromosome-positive
      acute leukemia (Ph+ AL) and treated those patients with BHAC-DMPV induction
      chemotherapy. After obtaining complete remission, we attempted to treat with
      allogeneic bone marrow transplantation, while those without suitability for
      marrow transplantation were treated with alpha-interferon (IFN-alpha), in order
      to obtain prolong remission status. Chromosomal and molecular analyses, including
      BCR rearrangement and BCR -ABL mRNA, before and after IFN-alpha treatment
      demonstrated a recovery of normal hematopoiesis by the treatment of INF-alpha,
      however, suppressive effect for the blast cells by IFN-alpha was insufficient. To
      clarify the mechanism of IFN-alpha on the Ph+ leukemia cells, we studied
      expression of interferon stimulated genes (ISGs). However, an association between
      expression of ISGs and therapeutic effectiveness was not evident. Although, the
      exact anti-neoplastic mechanism of IFN-alpha is not established yet, our study
      demonstrated the possibility for utilization of IFN-alpha in some Ph+ AL patients
      as a maintenance therapy to obtain long survivals. Therefore, studies using a
      large number of patients with Ph+ AL should be performed, in order to establish
      induction and maintenance therapies reflecting biological characteristics of Ph+
      AL.

PMID- 8158847
TI  - [Diagnosis and treatment strategy for de novo AML with trilineage
      myelodysplasia].
AB  - The findings of morphologically dysplastic features in hematopoietic cells in de
      novo AML has been known as AML with trilineage myelodysplasia (AML/TMDS). We
      analyzed the clinical data and treatment outcomes of 230 de novo AML patients
      treated with the Japan Adult Leukemia Study Group AML-87 protocol. Forty (17%)
      patients had AML/TMDS. It was detected in 21% to 34% of patients with M2, M4 and
      M6, and never seen in patients with M3 and M5. The median age was 48.5 years in
      the TMDS group and was 48 years in the patients without TMDS, respectively.
      Platelet count was higher in the TMDS group than that in the TMDS. AML/TMDS was
      also characterized by fewer blasts in the bone marrow. The complete remission
      (CR) rate was 63% and 81% in AML patients with and without TMDS, respectively;
      these rates being significantly different (p = 0.05). The predicted 5-year
      survival rate of the 40 patients with TMDS was significantly worse than that of
      the 190 patients without TMDS (9% vs 33%, p = 0.0005). The multivariate analysis
      revealed that the AML/TMDS was an unfavorable factor in the achievement of CR and
      in the prediction of longer survival.

PMID- 8158848
TI  - [Relationship between prognosis of multiple myeloma and response to VCAP
      therapy].
AB  - We investigated the relationship between response in M-protein to VCAP therapy
      and survival duration in 50 multiple myeloma (MM) patients who survived for at
      least 6 months. The relationship between improvement of hemoglobin level as a
      response of VCAP therapy and survival duration was also assessed. The survival
      time in patients whose M-protein was reduced by 50% or more within 6 months after
      therapy was shorter than that in patients in whom the reduction of > or = 50% or
      more was obtained in more than 6 months. Patients with a hemoglobin level of 10
      g/dl or higher before therapy survived significantly longer than those with a
      hemoglobin level of less than 10 g/dl. Among the patients with a hemoglobin level
      of less than 10 g/dl, patients in whom the hemoglobin level improved to 10 g/dl
      or higher survived for significantly longer duration than patients without
      improvement (p < 0.01). Patients in whom the hemoglobin level improved after more
      than 6 months survived form significantly longer duration than patients in whom
      hemoglobin level improved within 6 months. Therefore, it was considered that it
      was difficult to predict prognosis from the rate of decrease in M-protein in the
      early stage of treatment.

PMID- 8158849
TI  - [The clinical effect of factor XIII on drug-induced hemorrhagic cystitis].
AB  - The therapeutic effects of Factor XIII (F XIII) concentrate against drug-induced
      hemorrhagic cystitis (HC) was investigated. HC occurred in 4 children with
      malignant disease during anti-cancer chemotherapy. Two (CML and T-ALL) of 4
      patients developed HC after the administration of high dose cyclophosphamide as
      conditioning for allo bone marrow transplantation or peripheral blood stem cell
      autografts, and the other 2 patients (rhabdomyosarcoma, Wilm's tumor) developed
      HC after the administration of ifosfamide for relapse. When F XIII concentrate at
      a dose of 20 to 230 U/kg was administrated immediately after the onset of HC, the
      symptoms, i.e., bladder irritability and macrohematuria disappeared within a few
      days. The F XIII serum levels of those patients were low (27-57%), and the levels
      increased (63-230%) after administration of F XIII concentrate. The two patients
      with relapsed solid tumor showed no symptoms of HC during subsequent ifosfamide
      treatment when F XIII concentrate was administrated to maintain a normal F XIII
      range. These results suggest that the administration of F XIII concentrate may be
      useful for the prophylaxis and treatment of drug-induced HC in patients with a
      low F XIII level.

PMID- 8158850
TI  - [A case of pure red cell aplasia associated with sodium valproate therapy].
AB  - We reported a 14-year-old female with petit mal epilepsy who suffered from pure
      red cell aplasia 12 weeks after sodium valproate (VPA) therapy started. On
      admission she presented anemia but no jaundice. Her hemoglobin was 5.4g/dl and
      bone-marrow biopsy revealed hypocellularity with erythroid hypoplasia. The Direct
      Coombs' test and anti-nucleotide antibody were positive. Reticulocytosis occurred
      10 days after discontinuation of VPA. The Direct Coombs' test became negative one
      year after discontinuation of VPA. In general, drug-induced PRCA is caused by
      toxic or allergic agents, but this case suggests the immune mechanism of VPA
      induced PRCA.

PMID- 8158851
TI  - [Aggressive myeloma with subcutaneous tumor and pericardial involvement].
AB  - A 67-year-old male was admitted to our hospital because of anemia,
      thrombocytopenia, and renal failure. On admission he showed splenomegaly and
      elevated serum LDH level. Bone marrow showed hypercellularity with massive
      infiltration of lymphoblastoid cells. He was diagnosed as having multiple myeloma
      (BJ-kappa, stage IIIB). He transiently responded to intensive chemotherapy (VAD,
      MP, IFN alpha) but relapsed with multiple subcutaneous tumors and pericardial
      effusion. This is a rare case that the myeloma cell invasion to pericardial space
      was diagnosed before his death. The level of interleukin 6 (IL-6) in pericardial
      effusion was 16382 pg/ml, and the myeloma cells obtained from the pericardial
      effusion responded to IL-6, which suggested that high level of IL-6 closely
      related to the proliferation of myeloma cells in this case.

PMID- 8158852
TI  - [Infection-induced transient increase in the platelet count, and a transient
      remission of thrombocytopenia with high-dose intravenous gammaglobulin therapy
      during intercurrent pneumonia in chronic idiopathic thrombocytopenic purpura].
AB  - A patient with chronic idiopathic thrombocytopenic purpura (ITP), who had a
      transient increase in platelet count during infectious episodes, and had a
      transient remission of thrombocytopenia with administration of high-dose
      intravenous gammaglobulin during intercurrent pneumonia was described. A 64-year
      old Japanese woman with a 12-year history of chronic ITP was refractory to
      steroids and azathioprine, and the platelet count was constantly less than 10 x
      10(9)/l. During both acute upper respiratory infections and chronic cystitis due
      to E. coli, the platelet count transiently increased to more than 40 x 10(9)/l.
      High-dose intravenous gammaglobulin therapy successfully induced a remarkable
      increase in the platelet count, which persisted for 3 months, when gammaglobulin
      was administered during the intercurrent pneumonia. The bleeding tendency
      disappeared and transient remission of ITP was obtained. In contrast, the
      clinical efficacy of high-dose intravenous gammaglobulin proved to be only
      transient and slight, when administered before the onset of pneumonia or after
      recovery from pneumonia. These phenomena may suggest that high-dose gammaglobulin
      may enhance some positive mechanisms related to platelet increment in infectious
      diseases accompanied with chronic ITP.

PMID- 8158853
TI  - [Urinary bladder carcinoma was induced in a patient treated with cyclophosphamide
      for malignant lymphoma].
AB  - A case of urinary bladder carcinoma in a patient with malignant lymphoma (ML)
      involving the thyroid gland, gastrointestinal tract and the gallbladder is
      reported. The histological type of ML from the biopsy specimens of the thyroid
      gland and the stomach was non-Hodgkin's, diffuse large cell lymphoma of B cell
      origin. The patient had been treated for ML with cyclophosphamide (CPM),
      doxorubicin, vincristine and prednisolone effectively then maintained with low
      dose CPM. Two and a half years after the initial therapy, urinary bladder tumor
      diagnosed transitional cell carcinoma histologically was found. The patient had
      received 55 gr. of CPM totally. The dose of CPM was relatively smaller than the
      one in the other second cancer cases reported induced by CPM previously. It may
      be suggested that the urinary bladder carcinoma induced by CPM is related not
      only total dose of CPM but also the other factors. Thus usage of CPM must be
      cautious because of the secondary disease.

PMID- 8158854
TI  - [Allogeneic cryopreserved marrow transplantation in a patient with chronic
      myelogenous leukemia].
AB  - A 45-year-old male with chronic myelogenous leukemia received cryopreserved
      allogeneic bone marrow from his HLA-identical sister. Bone marrow was harvested
      and cryopreserved prior to chemoradiotherapy since the donor had neurotic
      tendencies. The preconditioning regimen consisted of standard dosage of busulfan
      plus cyclophosphamide and total lymphoid irradiation (5Gy). A total of 3.1 x
      10(7)/kg marrow mononuclear cells, containing 4.7 x 10(5) CD34+ cells/kg, and 8.0
      x 10(6)/kg buffy coat cells collected from the donor at day 0 was infused. Marrow
      engraftment occurred by day 38 although hematological recovery was delayed and
      subsequent administration of GM-CSF, methylprednisolone and donor buffy coat
      cells were required. Mononuclear cells obtained from the patient's blood at day
      28 had an inhibitory effect on CFU-GM formation of the donor's bone marrow
      mononuclear cells. We considered that this case suffered from a transient
      myelosuppression due to residual host cells after bone marrow transplantation.

PMID- 8158855
TI  - [Psoriasis exacerbated by alpha-interferon therapy in a case of chronic
      myelogenous leukemia].
AB  - A 49-year old male with chronic myelogenous leukemia (CML) and psoriasis was
      admitted for interferon treatment. He was given 6 MU of human lymphoblastoid
      interferon (HLBI), a natural alpha-interferon, daily for 1 month followed by 3 MU
      every other day for 1.5 months and twice a week for 1 month. Because HLBI
      administration showed no favorable effects on the hematological findings and
      because of the exacerbated psoriasis of the patient, it was discontinued.
      Subsequently his psoriasis improved to the initial findings observed at the
      admission. We reported a case of CML in which psoriasis was exacerbated during
      interferon therapy.

PMID- 8158856
TI  - Surgical treatment of stage III lung cancer after chemotherapy and radiotherapy.
AB  - We have experienced eight patients with advanced bronchogenic carcinomas who
      underwent resectional surgery after receiving preoperative adjuvant chemotherapy
      and radiotherapy during the period March, 1990, to February, 1992. Four patients
      were in stage IIIA and four in stage IIIB, of which six had epidermoid carcinomas
      and two small cell carcinomas. All patients were male with ages ranging from 48
      to 73 (mean 56.7) years. The induction chemotherapy for six patients consisted of
      cisplatin and VP-16 (Etoposide) only, and two patients were given
      fluorouracil/cyclophosphamide and cyclophosphamide/adriamycin/cisplatin in
      addition to cisplatin/VP-16, respectively. All patients also received four to six
      weeks of radiotherapy following chemotherapy and were re-evaluated for the
      possibility of surgery after four weeks of observation. All patients underwent
      pneumonectomies. Postoperative histological staging revealed complete responses
      in two patients, partial responses in three and no response in three. Patients
      were followed-up for seven to 33 (mean 21.5) months after the diagnosis of lung
      cancer. Six patients died 1, 2, 3, 10, 14 and 26 months postoperatively and two
      patients are alive, revealing no evidence of tumor recurrence 24 months
      postoperatively. Induction therapy may induce a better resectability by the
      conversion of the lung cancer to a lower clinical stage by the time of surgery.

PMID- 8158857
TI  - Myelodysplastic syndrome associated with immunoblastic lymphadenopathy-like T
      cell lymphoma: simultaneous clinical improvement with chemotherapy.
AB  - A 75-year-old woman presented with anemia, lymphadenopathy, hepatomegaly and
      lingual tumor, but no constitutional symptoms. The laboratory data showed
      pancytopenia and polyclonal hypergammaglobulinemia. A bone marrow aspirate
      represented an apparent myelodysplastic syndrome (MDS) feature, specifically,
      refractory anemia with excess of blasts. A lymph-node biopsy revealed the
      disappearance of normal architecture, small arborizing blood vessels, large
      lymphoid cells with prominent cytoplasm (so-called pale cells) and a clonal
      proliferation of T-lymphocytes. The patient was diagnosed as having MDS
      associated with immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma. She was
      subsequently treated with cyclophosphamide, adriamycin, vincristine and
      prednisolone for lymphoma which successfully induced a remission of not only the
      T-cell lymphoma but also the MDS. The case suggested that MDS might be a
      paraneoplastic complication of IBL-like T-cell lymphoma.

PMID- 8158858
TI  - Hepatocellular carcinoma with splenic metastasis developing after 16 years of
      chemotherapy for chronic myelogenous leukemia: a case report.
AB  - A case of hepatocellular carcinoma (HCC), which developed during chemotherapy for
      chronic myelogenous leukemia (CML), is presented. A 55-year-old Japanese man, who
      had received an alkylating agent for 16 years, was diagnosed as having HCC with
      clinically evident splenic metastases. The patient died of the HCC rupture three
      months after diagnosis. The autopsy revealed the HCC to have developed from the
      non-cirrhotic liver. In the present case, DNA damage due to the long-term
      chemotherapy with the alkylating agent for CML may have endowed the HCC induced
      by post-transfusion hepatitis and alcohol abuse with an aggressive proliferative
      potential. This is the first report on HCC in association with CML.

PMID- 8158859
TI  - Significant increases in serum CA125 and CA19-9 following torsion from an
      adenofibroma of the ovary: a case report.
AB  - Significant increases in the serum levels of cancer antigen 125 (CA125) and
      carbohydrate antigen 19-9 (CA19-9) were observed over one month prior to the
      removal of an ovarian adenofibroma. The serum levels of CA125 and CA19-9
      decreased rapidly after surgery. The surface of the tumor at surgery showed
      marked inflammation, probably induced by the necrosis produced by torsion.
      Pathologically, most of the tumor was necrotic, and histoimmunochemical staining
      of the viable cells was weak for CA125 but intense for CA19-9.
      Clinicopathological observations of the case suggested that CA125 and CA19-9
      might be stimulated in the cells by inflammation or that originally existing
      CA125 and CA19-9 were released from the tumor cells following the cell necrosis.

PMID- 8158860
TI  - Cell cycle assessment of adoptive transferred lymphokine activated killer cells.
AB  - The use of lymphokine activated killer (LAK) cells for adoptive transfer therapy
      has been reported from number of clinical trials. To our knowledge, however,
      there has been no report concerning the cell cycle progression of LAK cells.
      Thus, for the present study we have attempted to examine the LAK cell cycle
      either before or after transfer. In vitro and in vivo analyses of LAK cells
      labeled with bromodeoxyuridine (BrdU) were carried out using two-parameter flow
      cytometries of their nuclear staining using fluorescein isothiocyanate(FITC)
      conjugated anti-BrdU antibody and propidium iodide (PI). The in vitro growth of
      BrdU-positive cells showed the cells to divide once in the S phase, continue to
      the G2-M phase and return to the G0-G1 phase with a similar pattern after 48 or
      72 h culture. They formed a definite subpopulation and were of phenotypes, thy
      1.2 (+), Lyt-1.1 (-), Lyt-2.1 (+), L3T4 (-) and AGM1 (+). The percentage of BrdU
      positive cells decreased significantly (P < 0.05) when treated with complement
      plus anti-thy-1.2, anti-Lyt-2.1 or anti-AGM1 anti-bodies, demonstrating BrdU
      labeled LAK cells to have the same phenotype as control LAK cells. As in vitro,
      the in vivo cell cycle of LAK cells 48 and 72 h after transfer had a similar
      pattern, and the LAK cells also continued on to the S phase after the first
      division. The in vivo growth of the LAK cells treated with interleukin-2 (IL-2)
      was promoted 24 and 48 h after transfer. In conclusion, the present study showed
      LAK cells to be capable of dividing following transfer and to keep their own
      phenotypic characteristics; also, that treatment with IL-2 may promote their
      division. Adoptive transfer therapy seems to be a viable therapeutic method.

PMID- 8158861
TI  - Accuracy of computed tomography in determining pancreatic cancer tumor size.
AB  - We compared tumor sizes determined by computed tomography (CT) with those of the
      resected specimens in 26 patients with pancreatic cancer in order to clarify
      whether or not the size of a pancreatic tumor can be accurately determined by CT.
      From the precontrast, postcontrast and arterial dominant phases of dynamic CT,
      the arterial dominant phase was found to yield the highest correlation between CT
      measured tumor size and that of the resected specimens (P < 0.01). The
      correlation coefficient was, however, not high (r = 0.67). CT alone may therefore
      be insufficient to determine tumor size in pancreatic cancer accurately.

PMID- 8158862
TI  - Salivary gland neoplasms in children.
AB  - We reviewed 20 children with salivary gland neoplasms treated at the National
      Cancer Center Hospital between 1964 and 1990. Retrospective analyses of
      pathological features and the clinical courses of these cases constituted the
      bases of the present study. The age of onset was late childhood in 19 cases,
      ranging from 9 to 20 years, but one patient was 1 year old. Approximately half
      (55%) the neoplasms were malignant. Histologically, all the benign neoplasms were
      pleomorphic adenomas (nine cases) and the most common malignant neoplasm was
      mucoepidermoid carcinoma (six cases, 55%), followed by adenocarcinoma (three
      cases, 27%), adenoid cystic carcinoma (one case, 9%) and malignant mixed tumor
      (one case, 9%). Recurrences of pleomorphic adenomas occurred only in the three
      patients initially treated with enucleation; meanwhile, five patients treated
      with superficial parotidectomy, and one with submandibular glandectomy, had no
      recurrence. Recurrences of malignant tumors occurred in all six patients
      initially treated with enucleation only and in one with superficial parotidectomy
      but not in two patients treated with total parotidectomy. In seven patients
      treated with prophylactic neck dissection, no metastasis was identified
      pathologically. The results support no enucleation of the tumor being applied at
      the first operation for curing both benign and malignant salivary gland tumors.
      The indication for radical neck dissection appears to be limited.

PMID- 8158863
TI  - Concomitant chemoradiotherapy for advanced head and neck cancer.
AB  - Head and neck cancer is mostly curable in the early stages by either surgery or
      radiotherapy alone, but the control rate for advanced stages is low, even with
      combined surgery and postoperative radiotherapy. From September, 1990, to
      January, 1992, 35 patients with locoregionally advanced head and neck cancers
      were entered in a prospective study of concomitant chemoradiotherapy. Thirty
      three completed the treatment. There were 29 males and four females with a median
      age of 53 years. All except one patient were in stage IV. Radiotherapy was
      delivered using a telecobalt unit and by conventional fractionation (1.8
      Gy/fraction, 5 fractions/wk). Chemotherapy with cisplatin (10 mg/m2/day, daily,
      days 1-5) and 5-FU (500 mg/m2/day continuously infused for five days) was given
      concurrently during the first and fifth weeks of radiation. Twenty-four among 31
      eligible patients achieved complete response (77.4%) and the other seven (22.6%)
      partial response, resulting in a 100% response rate. The toxicities experienced
      were increased compared with those caused by radiotherapy alone. The most common
      side effects were gastrointestinal and hematologic toxicities but the whole
      treatment was well tolerated. The two-year actuarial survival rate is 45%. We
      found the primary origin and overall treatment time to affect survival
      significantly. The survival rate for tumors arising from the nasopharynx or
      paranasal sinus is better than for those arising from other regions of the head
      and neck. The shorter treatment times (within eight weeks) had a better survival
      rate. Our preliminary experience suggests that concomitant chemoradiotherapy is
      both feasible and effective for head and neck cancer. The optimal scheduling and
      dosage of concomitant chemoradiotherapy should be further researched.

PMID- 8158864
TI  - [Background of cardiovascular diseases in adult--with special reference to
      metabolic disorder of glucose and hypertension].

PMID- 8158865
TI  - [Cardiovascular surgery in elderly patients].

PMID- 8158866
TI  - [Surgical treatment of elderly patients with bronchogenic carcinoma].

PMID- 8158867
TI  - [Operative indications and treatment in elderly patients with esophageal cancer].
AB  - A recent study indicates that infection of human papillomavirus (HPV) may cause
      esophageal cancer and that it takes several decades from infection of HPV to
      developing cancer. Even in early stage esophageal cancer, lymph node metastasis
      is usually observed in the mediastinum, abdomen and neck regions. As patients
      with esophageal cancer are potentially in a malnutritional state because of
      disturbance of intake before treatment, active nutritional support should be
      performed before and after surgery. An objective nutritional assessment is
      necessary for nutritional support. The nutritional assessment index (NAI) can be
      applied to elderly patients because there is no difference in nutritional
      parameters between elderly and young patients. From the point of view that
      surgical treatment has limitations concerning complete curability, we employed a
      remote after loading system (RALS) into a multidisciplinary treatment called the
      Kochi system, which consists of a combination of surgery, radiation therapy and
      chemotherapy. This multidisciplinary method of treatment greatly contributes to
      survival and quality of life of esophageal cancer patients especially in elderly
      cases.

PMID- 8158868
TI  - [Evaluation of surgical treatment of gastric cancer in the aged].
AB  - Patients with gastric cancer aged 70 years or over were divided into 3 age groups
      (70-74, 75-79, 80 years or over) and were compared with patients aged 60-69
      years, (which is the age group with the highest incidence of stomach cancer) with
      regard to the incidence of postoperative complications. In addition, factors
      which might be associated with increased mortality were investigated. There were
      no significant differences with regard to the incidence of postoperative
      complications (16-21%) or the mortality rate (0-3%, within 30 days after surgery)
      between the various age groups. However, the incidence of those complications
      which later proved fatal was higher in those aged 75 years or over. Factors
      associated with the development of complications in each age group were the type
      of surgical technique used, the operation time, and the severity of hemorrhage
      during surgery. The prognosis for gastric resection was poor in patients aged 80
      years or over. Our findings indicated that curative resections should be
      performed for gastric cancers in the elderly if the general physical condition of
      the patients permits. A more conservative approach is desirable when the general
      condition is not favorable.

PMID- 8158869
TI  - [Surgical management of hepatic disorders in the elderly].

PMID- 8158870
TI  - [Health problems of elderly patients in a rural area].
AB  - The purpose of this study was to identify diseases frequently found in elderly
      populations in rural areas as well as to discuss the role of geriatric physicians
      in medical care for elderly patients. The study was conducted using ICHPPC-2
      Defined (Japan version) which had been compiled by WONCA for the classification
      of diseases. The acute health problems treated by the clinic consisted of 183
      types (2070 items) in 1916 patients seen during 19 months compared to 66 types of
      chronic problems consisting of 505 items in 179 patients. The most frequent acute
      complaints and health problems were acute infections of the upper respiratory
      tract, followed by diseases of the stomach and duodenum, then osteoarthritis and
      allied conditions. The most common chronic health problems were uncomplicated
      hypertension, osteoarthritis and allied conditions, osteoporosis, lipid
      metabolism disorders, complicated hypertension, cataract, and various other
      illnesses extending over all specialties of medicine. Geriatric physicians are
      required to have broad and multidisciplinary knowledge and skill to provide
      comprehensive and continual medical care for elderly patients in rural areas.

PMID- 8158871
TI  - [Effect of aging on the aerobic capacity measured by a step-test].
AB  - The purpose of this study was to develop a step-test in order to evaluate age
      related change in aerobic capacity. A total of 149 healthy men of age through 18
      to 83 yrs ascended and descended a single step of 0.2 m height in time to a
      metronome. The step rate increased step-wise through three stages, each of 3 min
      duration; 15, 20 and 25 (step/min) for subjects aged 59 or less, and 10, 15, and
      20 (step/min) for those age 60 and over. Using the linear relationship between
      load and heart rate, physical work capacity (PWC, watt/kg) was estimated as the
      work load with maximum heart rate predicted by age (220-age). In the elderly
      group (n = 34), heart rate at the end of the last stage was within 60-80% of the
      maximum heart rate for 25 subjects, and more than 80% for the other 9 subjects.
      No risky arrhythmia or significant ST change on ECG appeared in any subject. A
      retest of the step-test for 16 elderly subjects showed its repeatability and a
      linear relationship between heart rate and oxygen consumption. The results
      suggested that the step-test was applicable to the elderly in regard to
      appropriate work load and safety. The PWC significantly declined with aging (r =
      0.52, p < 0.001). Relative aerobic capacity, taking that at age 20 as 100%, was
      60% and 53% for subjects aged 60 and 70, respectively, which was in good
      agreement with available reports which measured oxygen consumption directly.

PMID- 8158872
TI  - [Therapeutic effect of lisuride maleate on post-stroke depression].
AB  - Twenty post-stroke depressive patients who obtained more than 11 points on Self
      Rating Questionnaire for Depression, were treated with 0.075 mg/day lisuride
      maleate for 12 weeks. The drug effect on depression was evaluated quantitatively
      by the Hamilton Rating Scale for Depression. The relationships between brain CT
      or MRI and SRQ-D score were investigated in 24 subjects. More than 80% of post
      stroke depressive patients improved after lisuride maleate treatment for 8 or 12
      weeks. In particular, depressed mood, hypobulia, sleep disturbance, anxiety, etc.
      were significantly improved compared to the baseline condition. As for the
      relationships with CT and/or MRI findings, the group with moderate to severe
      brain atrophy had a significantly higher grade of depressive state than those
      without.

PMID- 8158873
TI  - [A study of anemia and life activity in the elderly].
AB  - One hundred senior citizens aged 80 years and over in homes for the aged were
      evaluated for the incidence of anemia (hemoglobin under 11.0 g/dl), Hb
      concentration, serum iron, and total iron binding capacity (TIBC). The subjects
      were classified into different groups according to age distribution (80-84, 85
      89, over 90), as well as sex and life activity levels. In the 80-84 year age
      group, the Hb concentration was 0.5 g/dl higher than that in the other age
      groups. The Hb values of the male subjects were 1 g/dl higher than the
      corresponding values for female subjects. Subjects classified as bedridden had Hb
      values 1.2 g/dl lower than those in the groups that had higher activity levels (p
      < 0.001). The incidence of anemia was independent of sex and age differences;
      however, differences in activity levels were significant (p < 0.001). There are
      53 patients with some diseases, urinary tract infections, bed sores (over 3 cm
      diameter), chronic bronchitis, progressive cancers and chronic rheumatoid
      arthritis, which may be origins of anemia. Seventy six percent of bedridden
      patients have one or two of the above diseases and 30% of non-bedridden patients
      have these diseases. The difference was statistically significant (p < 0.001). In
      the bedridden group, the differences of the mean Hb levels and the rates of
      anemia in patients with and without disease were not statistically significant (p
      > 0.1 in both factors). These facts indicate that the bedridden elderly have a
      high risk of anemia which is independent of some infectious and malignant
      diseases.

PMID- 8158874
TI  - Progression of renal disease. Tiberias, Israel, June 20-22, 1993. Proceedings.

PMID- 8158875
TI  - Energy metabolism following reduction of renal mass.

PMID- 8158876
TI  - The role of lymphocytes in the progression of interstitial disease.
AB  - Chronic interstitial disease is a major cause of end-stage renal failure. The
      process is characterized mainly by tubular atrophy and interstitial fibrosis and
      may be the result of primary or secondary interstitial nephritis. The secondary
      form attends almost all instances of progressive glomerular and vascular
      diseases, determining in a large part their outcome. Both forms of interstitial
      nephritis are initially characterized by the presence of mononuclear infiltrates
      with the majority being T lymphocytes. The predominance of CD4+ or CD8+ T-cells
      depends on the underlying cause. Both cell types may lead directly or indirectly
      to the induction of tubulointerstitial fibrosis. Direct stimulation of
      fibroblasts to proliferate and produce extracellular matrix may be caused by TGF
      beta, IL-4, TNF-alpha, and other fibroblast stimulating factors. Indirect
      induction of fibroblasts is mediated by stimulation of monocytes/macrophages
      through IL-2 and IFN-gamma. Furthermore, T cells may directly interact with
      epithelial cells, leading, for example, to a decrease in type IV collagen
      production in these cells, thus contributing directly to tubular atrophy. The
      role of MHC class II expression on tubular epithelial cells in the process of
      chronic interstitial disease remains to be fully elucidated.

PMID- 8158877
TI  - Glomerular volume expansion and mesangial cell mechanical strain: mediators of
      glomerular pressure injury.

PMID- 8158878
TI  - The role of oxidants in progressive renal injury.

PMID- 8158879
TI  - Renal endpoints in non-diabetic patients.

PMID- 8158880
TI  - Outcome variables in the assessment of progression of diabetic kidney disease.

PMID- 8158881
TI  - Hypercholesterolemia--a determinant of renal function loss and deaths in IDDM
      patients with nephropathy.
AB  - The development of kidney disease in diabetes mellitus can be viewed as a two
      stage process: (1) the development of proteinuria, and (2) its progression to
      chronic renal failure. Determinants of the latter were examined in 439 IDDM
      patients who had nephropathy and participated in the Diabetic Retinopathy Study.
      Using serum creatinine levels obtained during the follow-up period to assess the
      rate of loss of renal function, we found that only one-third of these patients
      experienced a rapid loss of function, while the others had slowly declining or
      unchanging renal function despite the presence of proteinuria and severe diabetic
      retinopathy. Among the many baseline variables examined, only elevated
      cholesterol and elevated systemic blood pressure were predictors of a rapid loss
      of renal function. Patients with this rapid loss of renal function also had the
      highest risk of death due to cardiovascular causes, as well as all causes. Once
      again, hypercholesterolemia was the major predictor of these deaths. In
      conclusion, efforts should be undertaken early to identify patients who are
      rapidly losing renal function so that interventions to modify systemic blood
      pressure and hypercholesterolemia may prevent or postpone the development of
      renal failure and death in patients with IDDM.

PMID- 8158882
TI  - Ambulatory blood pressure and abnormal albuminuria in type 1 diabetic patients.
AB  - In healthy individuals compared to normoalbuminuric patients, day time blood
      pressure (BP) is indistinguishable between the groups in most studies, while a
      slightly higher nocturnal systolic BP is a common finding. Despite a comparable
      clinic BP both day and night BP are higher in microalbuminuric patients, and the
      diastolic night/day ratio is clearly elevated as compared with healthy controls.
      In normo- and microalbuminuric patients ambulatory blood pressure (AMBP)
      correlates with urinary albumin excretion (UAE). The evolution of AMBP in a three
      year follow-up study presented evidence that in healthy individuals the increase
      in 24 hour systolic BP was approximately 1 mm Hg per year and was almost
      identical to the increase in persistent normoalbuminuric patients. In contrast,
      patients who progressed to microalbuminuria exhibited a fourfold higher increase
      in 24 hour AMBP compared to the persistent normoalbuminuric patients. Ordinary
      clinic measurements did not reveal this difference. There was no difference in
      initial 24 hour AMBP in progressors and non-progressors. Our study favors the
      concept of a simultaneous rise in BP and UAE. In overt renal disease, AMBP is
      significantly higher than in microalbuminuric patients. The circadian variation
      of blood pressure is blunted particularly in patients with advanced diabetic
      nephropathy and antihypertensive treatment. AMBP in type 1 diabetic patients
      allows: (1) the detection of minor but clinical relevant elevations of BP; (2) to
      disclose and association between BP and UAE in cross sectional studies; (3) to
      give a description of the blunted diurnal BP rhythm in patients with incipient or
      overt diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158883
TI  - Long-term enalapril treatment in diabetic nephropathy.
AB  - A randomized comparison of enalapril and metoprolol in patients with type 1
      diabetes and nephropathy showed that the decline in kidney function was 5.6 +/-
      5.9 ml/min/year in the metoprolol-treated and 2.0 +/- 3.2 ml/min/year in the
      enalapril-treated patients (P = 0.02). In the present study, the enalapril
      treated patients have been studied for two additional years. In the metoprolol
      treated group, only the endpoints of death or uremia have been recorded, and six
      of the patients have reached end-stage renal failure and three are dead, compared
      to three and two, respectively in the enalapril treated group. The mean fall in
      glomerular filtration rate in 18 enalapril-treated patients is 8.4 +/- 9.4
      ml/min/1.73 m2 after four years; 7.5 +/- 9.8 ml/min/1.73 m2, occurred during the
      first six months treatment. The mean decline in kidney function was 1.7 +/- 2.4
      ml/min/year over the whole study period and 0.3 +/- 3.9 ml/min/year after
      exclusion of the first six months. In this study, long-term enalapril treatment
      in diabetic nephropathy was associated with a low rate of decline in kidney
      function.

PMID- 8158884
TI  - Reduction in albuminuria predicts diminished progression in diabetic nephropathy.
AB  - We have evaluated putative predictors of the progression in diabetic nephropathy
      during long-term antihypertensive treatment. Twenty hypertensive insulin
      dependent diabetic patients with nephropathy were followed for three (2 to 5)
      years before, and for three years during antihypertensive treatment with
      metoprolol and furosemide. Fall rate in glomerular filtration rate (GFR) was 9.5
      +/- 3.8 ml/min/year (mean +/- SD) before and 3.6 +/- 3.6 during antihypertensive
      treatment. Albuminuria was 1442 (150 to 7564) micrograms/min (median range) in
      the last year before and 880 (96 to 3310) micrograms/min in the first year during
      treatment. Relative change in adjusted albumin excretion (ratio of values
      obtained during first year of treatment/and last year before) was significantly
      correlated to fall rate in GFR during the three years of treatment (r = 0.46, P <
      0.05) and to relative change in fall rate in GFR (fall rate during and before
      treatment were compared) (r = 0.47, P < 0.05). No significant correlations were
      found between fall rate in GFR during the three years of treatment and arterial
      blood pressure, albuminuria or GFR measured the last year before, the first year
      during treatment or the relative changes in these three variables (after-before).
      In conclusion, a decrease in fractional albumin excretion during conventional
      antihypertensive treatment predicts an attenuated fall rate in GFR in diabetic
      nephropathy. The finding suggests a clinical application in monitoring the
      efficacy of antihypertensive treatment in diabetic nephropathy.

PMID- 8158885
TI  - Renal protective effects of enalapril in hypertensive NIDDM: role of baseline
      albuminuria.
AB  - The primary results of a three-year prospective, double-blind, placebo-controlled
      trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti
      hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal
      function to a greater extent than therapy with antihypertensive agents excluding
      ACE inhibitors (J Am Soc Nephrol 3:335, 1992). The influence of baseline urinary
      albumin excretion on the renal protective effects of enalapril treatment in these
      subjects was the objective of this further analysis. Adequate data were available
      in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline
      glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m2]. Twenty-four hour
      urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and
      isotopically determined GFR were measured at baseline and six month intervals.
      Glycemic control and blood pressure regulation were assessed every three months.
      The rate of loss of GFR was significantly greater in patients with overt
      proteinuria at baseline (UAE > 300 mg/24 hr) as compared to patients with
      baseline sub-clinical proteinuria (UAE < or = 300 mg/24 hr). Antihypertensive
      treatment with enalapril preserved GFR significantly better (P < 0.01) in the
      patients with sub-clinical proteinuria at baseline (UAE < or = 300 mg/24 hr) than
      other antihypertensive treatments which excluded the ACE inhibitor. Furthermore,
      only 7% of the enalapril-treated group progressed to clinical albuminuria
      compared to 21% of control treated patients. Although the enalapril-treated group
      had a lower mean blood pressure during the maintenance period, no correlation
      between blood pressure (systolic, diastolic or mean arterial) and rate of change
      of GFR was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158886
TI  - Angiotensin converting enzyme inhibition in diabetic nephropathy. The
      Collaborative Study Group.

PMID- 8158887
TI  - Long-term effect of ACE inhibition on development of nephropathy in diabetes
      mellitus type II.
AB  - Ninety-four normotensive, type II diabetics with microalbuminuria and normal
      renal function were randomized to receive enalapril or placebo and were followed
      for five years. In the patients treated with enalapril, albuminuria decreased
      initially from 143 +/- 64 (mean +/- SD) mg/24 hours to 122 +/- 67 mg/24 hours,
      then a slow increase was observed to 140 +/- 134 mg/24 hours after five years. In
      the placebo group albuminuria increased from 123 +/- 58 mg/24 hours to 310 +/-
      167 mg/24 hours after five years. The difference between the rates of change in
      albuminuria over time in the two groups was highly significant (P < 0.005).
      Kidney function, expressed as mean reciprocal creatinine, declined by 13% in the
      placebo group and remained stable (-1%) in the enalapril group (P < 0.05). The
      initial value of daily albuminuria was a good predictor of the subsequent decline
      in renal function (r = 0.86, P < 0.001 and r = 0.72, P < 0.001 for the enalapril
      and the placebo groups, respectively). Initial and subsequent mean values of
      cholesterol and LDL were lower in the enalapril than in the placebo group. There
      was a close correlation between mean cholesterol values and the decline in renal
      function (r = -0.58, P < 0.001). The mean blood pressure was stable in the
      enalapril group (initial group mean 99 +/- 2.1 mmHg, fifth year mean 100 +/- 3.2
      mmHg) and increased in the placebo group from 97 +/- 3.2 mmHg to 102 +/- 3.4 mm
      Hg at the end of the study (P = 0.082).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158888
TI  - Prevention of progression in non-diabetic chronic renal failure.
AB  - We have performed separate randomized prospective controlled studies on the
      effects of protein-restricted diet and angiotensin converting enzyme (ACE)
      inhibition on the rate of progression of non-diabetic renal failure. Renal
      function was assessed by creatinine clearance, reciprocal of plasma creatinine
      concentration and 51Cr-EDTA clearance. A protein-restricted diet (0.4 g per kg)
      resulted in a significantly lower rate of progression, as assessed by the slope
      of these parameters with time, when compared with a standard diet. ACE
      inhibition, when assessed by a mixed effect model, also significantly reduced the
      rate of progression. The many variables involved hinder trials of therapies
      directed against progression in non-diabetic renal failure.

PMID- 8158889
TI  - The role of physical forces in alterations of mesangial cell function.

PMID- 8158890
TI  - Short-term antiproteinuric response to antihypertensive treatment predicts long
      term GFR decline in patients with non-diabetic renal disease.

PMID- 8158891
TI  - Spontaneous glomerulosclerosis: insights from the fawn-hooded rat.

PMID- 8158892
TI  - Internephron heterogeneity of growth factors and sclerosis.

PMID- 8158893
TI  - Glomerular hypertrophy and progressive glomerulopathy. Is there a definite
      pathogenetic correlation?

PMID- 8158894
TI  - Tumor necrosis factor alpha in glomerular injury.

PMID- 8158895
TI  - Vascular endothelial cell activation in models of vascular and glomerular injury.
AB  - Activated vascular endothelium evidences a diverse array of responses to
      biochemical and physical stimuli with modulating effects on leukocyte
      trafficking, vascular permeability and vasomotor tone controlling microvascular
      blood flow. Clearly, glomerular endothelial cells share in common with large
      vessel endothelium some components of the cytokine-activated phenotype. These
      findings provide insight into mechanisms of glomerular injury. Speculation about
      potentially unique aspects of microvascular regulation which might be important
      in glomerular injury suggests that novel aspects of cytokine-activation may be
      evident in microvascular endothelial cells. Molecular mechanisms underlying
      signal transduction of stimulus-induced alterations in endothelial phenotype
      implicate cis-regulatory processes that are unique in diversity and expression.
      Further elucidation of these mechanisms may suggest interventions directed
      towards inhibiting the pathophysiologic sequelae of endothelial cell activation.

PMID- 8158896
TI  - Does extracellular matrix expansion in glomerular disease require mesangial cell
      proliferation?

PMID- 8158897
TI  - Gene activation in glomerulosclerosis: a role for growth promoting hormones.

PMID- 8158898
TI  - Cholesterol synthesis inhibitors inhibit more than cholesterol synthesis.
AB  - The beneficial effects of HMG-CoA reductase inhibition in models of progressive
      glomerular injury may not all be due to reductions in circulating lipoproteins
      and decreases in glomerular lipoprotein deposition. Indeed, HMG-CoA reductase
      inhibitors may have direct effects on glomerular mesangial cells that could
      explain the amelioration of renal injury. Specifically, HMG-CoA reductase
      inhibitors block the synthesis of isoprenoids that are necessary for mesangial
      cell proliferation and other important cell functions. Thus, protein
      isoprenylation may play a critical role in the pathogenesis and treatment of
      lipid-induced glomerular injury.

PMID- 8158899
TI  - Cellular mechanism of glomerular injury: metabolic factors in progressive renal
      injury.

PMID- 8158900
TI  - How does glomerular epithelial cell injury contribute to progressive glomerular
      damage?
AB  - Glomerular visceral epithelial cells, unlike epithelial cells in other organs or
      in the more distal segments of the nephron, are highly differentiated, terminal
      cells that do not undergo cell division under physiological conditions in the
      postnatal period or during conditions that result in renal hypertrophy. Adjacent
      cells are connected to each other at the level of complex interdigitations or
      foot processes by filtration slit diaphragms. This particular arrangement
      contributes to the extremely high hydraulic conductivity of the normal glomerular
      capillary. Toxic and metabolic damage to the visceral epithelial cells or
      conditions of extreme glomerular hypertrophy result, in the short term, in
      diffuse or focal simplification and flattening of the foot processes. The areas
      of the capillary wall covered by such a simplified epithelium are likely to have
      a greatly reduced hydraulic conductivity which results from the greatly
      diminished surface area available for filtration. The rearrangement of foot
      processes also leads to focal areas of denudation of the basement membrane. Such
      denuded areas, however, are likely to result in an increase in local hydraulic
      flux, especially under conditions of capillary hypertension. Such defects have
      been shown to be the pathway of increased permeability to macromolecular markers
      and proteinuria. Large plasma proteins are retained in the subendothelium by the
      size-restrictive water-filled channels of the lamina densa and accumulate
      upstream in the form of hyaline which eventually occludes individual loops. More
      severe epithelial cell injury and denudation may also result in collapse of
      entire tuft segments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158901
TI  - The role of systemic and glomerular hypertension in progressive glomerular
      injury.

PMID- 8158902
TI  - The role of podocytes in the development of glomerular sclerosis.

PMID- 8158903
TI  - The mesangial matrix in the normal and sclerotic glomerulus.
AB  - Mesangial sclerosis is a final common pathway to glomerular destruction in a
      variety of glomerular diseases. The expression of several classes of
      extracellular matrix (ECM) molecules has been defined in the normal and diseased
      mesangial matrix (MM). However, the manner in which these ECM components
      determine the three dimensional structure and function of the MM remains to be
      defined. Structural studies of the MM suggest that its constituent molecules are
      regionally organized into subcompartments with different three dimensional
      structures. The diversity of matrix molecules expressed within the MM as well as
      the organization of these components in nonrenal ECM's, such as the cornea,
      provides further support for this organizational model. The study of the cornea
      has also revealed that novel short chain collagenous proteins partially determine
      the three dimensional structure of the matrix. Recently, a novel collagen, type
      VIII collagen, has been described in mesangial cells and in the intact
      glomerulus. It is hypothesized that type VIII collagen is expressed both as a
      polymer and as a monomer within the glomerulus, and depending on its
      conformation, may serve unique functions. In the chronically diseased MM, normal
      MM components are overexpressed and fibrillar collagens are expressed de novo in
      a delayed fashion. Enhanced proteoglycan expression, observed early in disease,
      may determine increased volume of the mesangium. This, in turn, may stimulate the
      production of fibrillar collagens by mesangial cells resulting in a fibrillar
      noncompliant mesangial matrix.

PMID- 8158904
TI  - Macrophages in renal injury.
AB  - There is good evidence from experimental studies that glomerular macrophages are
      important in acute renal injury and an increasing acceptance that they also play
      a role in chronic glomerular injury by stimulating mesangial cell proliferation
      and glomerulosclerosis. However, it is now evident that the contribution of
      macrophages and T cells within the interstitium must be taken into account.
      Indeed, if it is proved that progressive renal injury occurs via interstitial DTH
      mechanisms, regardless of the nature of the initial glomerular insult, then such
      mechanisms may provide a suitable target for the development of novel therapeutic
      strategies.

PMID- 8158905
TI  - Pivotal role of colony stimulating factor-1 in lupus nephritis.
AB  - Spontaneous autoimmune renal injury in MRL-lpr mice shares many features of human
      lupus nephritis. We noted a prominent increase of macrophages (M phi) in the
      glomerulus of MRL-lpr mice. Since colony stimulating factor-1 (CSF-1) regulates M
      phi growth and is a potent chemoattractant, we explored the possibility that
      there was an increase in CSF-1 in MRL-lpr mice. We detected a biphasic increase
      in circulating CSF-1 in MRL-lpr mice as compared to congenic MRL- ++ mice other
      strains with the lpr gene, and normal mice. There was an increase in CSF-1 steady
      state mRNA transcripts in the kidney but not in the liver, lung or bone marrow.
      By in situ hybridization our studies identified the glomeruli as the predominant
      source of renal CSF-1. Enhanced CSF-1 is expressed by the mesangial cells at the
      same time (4 weeks of age) that M phi begin to accumulate in the glomeruli, well
      in advance of the loss of renal function. We have isolated pure populations of
      glomerular M phi in culture from MRL-lpr mice. These glomerular M phi require CSF
      1 to survive and proliferate. Therefore, these data suggest that CSF-1 is
      increased in the glomerulus prior to the influx and accumulation of M phi. We
      propose that CSF-1 expression in the kidney is pivotal in the attraction and
      accumulation of M phi and in turn responsible for initiating tissue destruction.

PMID- 8158906
TI  - Integrin matrix receptors in renal injury.
AB  - Integrins play a major role in cell-matrix interactions. They alter cellular
      functions upon binding to matrix proteins or following cross linking and can in
      turn be regulated by other stimuli acting on the cell. In the kidney integrins
      may help regulate cellular proliferation and matrix turnover during renal injury,
      effects which could play an important role in the pathogenesis of
      glomerulosclerosis and the resultant loss of renal function. Alterations in cell
      adhesiveness may contribute to tubular epithelial cell sloughing and tubular
      obstruction in acute renal failure and may play a role in alterations of
      glomerular capillary wall permeability, leading to proteinuria. Adhesion
      molecules on GEC may be important targets of antibodies in several models of
      proteinuric renal disease and areas of GEC detachment from the GBM may be
      involved in the development of glomerulosclerosis. Since integrins are major
      links between the ECM and cells, better understanding of their function in the
      normal kidney and during injury is of importance to a better understanding of the
      pathogenesis of renal disease.

PMID- 8158907
TI  - Leukocyte adhesion promotes biosynthesis of lipoxygenase products by
      transcellular routes.

PMID- 8158908
TI  - [Changes in acid producing and motor-evacuatory functions of the stomach after
      median gastric resection].
AB  - Changes in the acid production and motility of a gastric stump in 108 patients
      after mediogastric pylorus-and-antrum preserving resection performed for ulcer
      disease of the stomach (72 patients) and duodenum (36) were studied. In most
      patients, 1-3 years later, a weak acid and moderate acid reaction was noted in
      the gastric body. Complete restoration of motor-evacuatory function of the
      stomach and duodenum occurred within 1 year.

PMID- 8158909
TI  - [Disorders of immune status in duodenal ulcer complicated by perforation and
      peritonitis].
AB  - The chemotaxic activity of neutrophil granulocytes was studied in 112 patients
      with duodenal ulcer disease complicated by perforation and peritonitis with a
      different degree of spreading. Sharp decrease in spontaneous migration of
      leukocytes (SML) was revealed in generalized peritonitis. In diffuse peritonitis,
      the index didn't differ from that in normal subjects. In patients with the
      complicated course of the postoperative period, SML stimulation under the
      influence of the own serum was noted. At day 3-9 after the operation, the
      stimulating activity of the humoral factors of immunity was gradually decreasing.
      Use of the stimulators of migrative activity of phagocytes contributes to
      normalization of their function. In patients who had the immunocorrigative agents
      been prescribed, aggravation of peritonitis and purulent-septic complications
      were noted 1.4-fold less often than in absence of such treatment.

PMID- 8158910
TI  - [Activity of alkaline phosphatase in the stomach content as a marker of function
      of gastrointestinal anastomosis after stomach resection].
AB  - In 77 patients with gastric ulcer disease, the activity of alkaline phosphatase
      of gastric juice and its fractions was studied at the late period after resection
      of the stomach. Activity of thermolabile and thermostable fraction of alkaline
      phosphatase was the lowest in patients who underwent creation of transverse
      Billroth-II anastomosis, indicating that it was more physiologic as compared to
      Hofmeister--Finsterer modification of anastomosis in relation to the barrier
      (sphincter) function, and thus prevented reflux of the intestinal contents into
      the stomach.

PMID- 8158911
TI  - [Analysis of causes of second laparotomy the planned surgery of stomach and
      duodenal ulcer].
AB  - In connection with the development of intraabdominal complications, 71 (4.3%)
      patients underwent relaparotomy. Peritonitis and intraabdominal abscess were the
      most frequent causes (61.9% of cases) of the repeated intervention. Lethality was
      29.5%.

PMID- 8158912
TI  - [Clinical aspects and surgical treatment of patients after closure of perforated
      duodenal ulcer].
AB  - The experience with treatment of 454 patients with the ulcer disease recurrence
      which occurred after closure of a perforative duodenal ulcer is presented.
      Disease recurrence developed in 83.9% of the patients, and was complicated in
      54.5% within the first 3 years after the operation. In 411 patients, gastric
      resection was performed using L. G. Khachiyev's technique which permitted to
      ensure safety of the duodenal stump sutures.

PMID- 8158914
TI  - [Surgical methods in recurrent peptic ulcer after vagotomy].
AB  - In treatment of recurrent and peptic postvagotomy ulcer, the performance of
      gastric resection is indicated. Of 53 patients with a recurrent ulcer, 20 had a
      "difficult" low penetrating ulcer. With the aim ot prevent duodenal suture
      failure, gastric resection in these patients was performed using the developed by
      the authors method which permitted to ensure safety of the single-layer suture of
      a duodenal stump with preservation of food passage through the duodenum. After
      truncal vagotomy with Jaboulay drainage operation, a defect in the duodenal wall
      was eliminated by means of creation of anastomosis with a gastric stump.

PMID- 8158913
TI  - [Surgical treatment of perforated ulcer of the stomach and duodenum].
AB  - The results of treatment of 188 patients with a perforative gastric and duodenal
      ulcer whithin the period of from 1981 to 1990 have been analysed.

PMID- 8158916
TI  - [New methods of vagotomy in the treatment of duodenal ulcer].
AB  - The experience to use in the treatment of duodenal ulcer disease the new methods
      of vagotomy: selective distal antral cellular vagotomy (SDAV) and selective
      distal vagotomy with pyloroplasty (SDV) is substantiated. By means of these
      operations, the suppression of phase II of gastric secretion is achieved due to
      denervation of gastrin-producing antral portion of the stomach. The results of
      experimental studies in 15 dogs, and the results of treatment of 37 patients with
      duodenal ulcer disease caused by the increased production at phase II of
      alimentation are presented. SDAV was performed in 20 patients, SDV--in 17. A
      result of treatment was studied in 34 patients at the period of up to 3 years. A
      pronounced acid inhibiting effect of the new methods of vagotomy was noted. No
      ulcer recurrence was revealed.

PMID- 8158915
TI  - [Lethality in postoperative thromboembolism of the pulmonary artery and methods
      of its therapy].
AB  - Of the 350 patients who died in 1978-1988 from pulmonary thromboembolism (PTE) in
      3 clinics of Ivano-Frankovsk, the surgical patients accounted for 36% (51.6% of
      them--at the age of 60 years and older). The likelihood of the PTE development is
      the highest during the first week after the operation performed, as a rule, for a
      malignant tumour of the alimentary organs, vascular diseases, and after
      prostatectomy.

PMID- 8158917
TI  - [Technical improvement of a method for the amputation of an extremity].
AB  - The investigations on 10 human cadavers, in the experiment--on 130 white rats and
      28 dogs, in the clinic--in 40 patients after amputation of an extremity,
      employing the conventional technique and that with the use of the neurotoms
      created which was developed, are presented. Dependence of the pain syndrome on
      different methods for neurectomy and their state in a stump was studied.

PMID- 8158918
TI  - [Methods to optimize local treatment of chronic non-healing wounds and trophic
      ulcers].
AB  - The results of experimental and clinical studies of the effectiveness of the use
      of algipore saturated with 1% dioxidine solution and 3 % tiotriasaline solution
      in local treatment of sluggish wounds and trophic ulcer are present.

PMID- 8158919
TI  - [Treatment of purulent and necrotic lesions of the lower extremities in patients
      with diabetes mellitus].
AB  - The results of complex treatment of 172 diabetic patients with purulent
      inflammatory lesions of the lower extremities, using intensive purposeful
      antibacterial and desintoxicative therapy, timely and sufficient opening of
      purulent foci as well as administration of desagregants, stimulators of
      reparative processes, anabolic hormones, vitamins etc., are presented. Correction
      of carbohydrate metabolism was performed by means of insulin therapy according to
      the optimized scheme. Use of UV irradiation of the blood of the patients and
      local antiinflammatory roentgenotherapy contributed to increase in effectiveness
      of treatment. Incidence of amputation of an extremity at a level of a thigh was
      20.2%, lethality-8.1%.

PMID- 8158920
TI  - [Diagnosis and surgical correction of dynamic hypertension in the inferior vena
      cava in varicose disease].
AB  - In 80% patients with varicose disease, the importance of dynamic hypertension of
      the inferior vena cava was studied by means of retrograde pelvic phlebography.
      Two types of pathologic caval reflux were revealed: the direct and indirect ones.
      In direct type, incompetence of the deep and communicative veins of the thigh,
      saphenofemoral anastomosis failure occur, in indirect one--anatypical form of the
      varicose disease.

PMID- 8158921
TI  - [Evaluation of effectiveness of programmed laparostomy in the treatment of
      diffuse suppurative peritonitis and peritoneal sepsis].
AB  - The results of treatment of 630 patients with peritonitis of different etiology
      are presented. In 170 patients with purulent peritonitis, the programmed
      laparostomy was used in the complex of treatment. A good immediate and long-term
      result was noted. Lethality reduced by 17.3%.

PMID- 8158922
TI  - [Assessment of the membrane properties of blood leukocytes in patients with
      purulent septic complications].
AB  - Osmotic resistance of leukocytic membranes was studied in 36 patients with
      purulent-septic complications and in 43 donors. As a damaging medium, 0.45%
      solution of sodium chloride was used. The cells were incubated in it for 30 min
      at a temperature of 37 degrees C. It was established that in purulent-septic
      complications, the structural-functional properties of leukocytes changed. This
      resulted in decreased resistance of their membranes.

PMID- 8158923
TI  - [Effectiveness of transthoracic puncture in the diagnosis and treatment of lung
      cancer].
AB  - The complex examination of 1400 patients with pathologic masses of the lungs and
      mediastinal organs with the use of roentgenologic, endoscopic, puncture bioptic
      and cytologic methods was carried out. Morphologic verification of diagnosis was
      performed in 93.7% of the patients. In express cytologic study, histogenesis of
      neoplasms of the thoracic cavity organs was specified in 97.9% of cases of a
      malignant tumour, and in 64.4% of those of a benign one.

PMID- 8158924
TI  - [Morphological changes of stomach innervation after vagotomy].
AB  - The morphologic signs of response of the peripheric neural system of the stomach
      to vagotomy in animals and in patients with the ulcer disease were compared. The
      innervative apparatus of the stomach was studied in 4 intact dogs (control), 6
      animals who underwent selective proximal vagotomy (SPV) and in 13 patients with
      the ulcer disease reoperated after SPV performance in connection with the
      development of a recurrent ulcer. Compensatory possibilities of the innervative
      apparatus of the stomach in human are lower than those in animals.

PMID- 8158925
TI  - [Malignant intestinal carcinoid].
AB  - A brief literature review of malignant carcinoids of the alimentary canal is
      given, the cases of malignant carcinoid of the ileum and cecum are presented.

PMID- 8158926
TI  - [Age factors in natural mechanisms of detoxication and curative effect of
      enterosgel in burns].
AB  - In the experiment, the age peculiarities of the detoxication system of the liver
      in burn disease and the effect of enterosgel on them were studied. Decrease in
      hydroxylase and demethylase activity of hepatic microsomes in relatively stable
      activity of oxidoreductase as well as increase in activity of aminotransferases,
      especially that of alanine aminotransferase, which was more pronounced in aged
      animals, was noted. Under the influence of enterosorption, the increase in
      functional activity of monooxygenase system of the liver and stabilization of
      hepatocytic membranes are more pronounced in young animals. This contributed to
      reduction in lethality, activation of natural mechanisms of detoxication and
      reparative processes.

PMID- 8158927
TI  - [Causes and risk factors of postoperative intraabdominal complications].

PMID- 8158928
TI  - [Excessive iliofemoral allograft causing diagnostic error].

PMID- 8158929
TI  - [Use of external fixation equipment for the treatment of obliterative
      endarteritis of the lower extremities].

PMID- 8158930
TI  - [A device for retraction of the surgical wound].

PMID- 8158931
TI  - [Surgery on the suprapapillar part of the common bile duct for obstructive
      disorders].

PMID- 8158932
TI  - [Plastic surgery of major veins in accelerated venous blood flow].

PMID- 8158933
TI  - [Successful treatment of severe multiple injury of the inferior vena cava in a
      patient with hemophilia].

PMID- 8158934
TI  - [Injury of the common carotid artery and internal jugular vein].

PMID- 8158935
TI  - [Isolated rupture of the left renal artery in closed abdominal injury].

PMID- 8158936
TI  - [Effectiveness of plasmapheresis in the combined treatment of suppurative
      wounds].

PMID- 8158937
TI  - [Rationale for the treatment of suppurative inflammatory disease of the skin and
      subcutaneous tissue in the medical clinic of a large industrial facility].

PMID- 8158938
TI  - [Abscessed omentitis simulating malignant tumor].

PMID- 8158940
TI  - [Laparoscopic diagnosis of torsion of the great omentum in a patient with acute
      pancreatitis].

PMID- 8158939
TI  - [Morphological changes and function of gastric and pancreatic mucosa after
      selective proximal vagotomy in patients with pyloroduodenal ulcer].
AB  - The pathomorphological changes in the gastric mucosa and acid production were
      studied in 118 patients with ulcer disease of a pyloric portion of the stomach
      and duodenum before and after selective proximal vagotomy in combination with
      drainage operation. Before the operation, the atrophic changes were the most
      pronounced in the gastric antrum. Increase in debit of chlorohydric acid was
      caused by increase in the volume of gastric juice and acid production.
      Stimulation with food contributes to considerable increase in gastrin
      concentration in the blood of the patients in low level of glucagon and insulin.
      Early after the operation, the signs of acute inflammation were revealed in the
      mucosa of the body and antrum. In increase of a basal level of gastrin and
      glucagon, acid production significantly decreased. Long-term atrophic gastritis
      of the body of a stomach was noted mainly in patients with delayed evacuation of
      its contents. Normalization of the level of hormones correlated with the indices
      of acid-producing function of the stomach.

PMID- 8158941
TI  - [Hemangioma of the ileum as a cause of intraabdominal hemorrhage].

PMID- 8158942
TI  - [Preoperative care and surgical techniques in the varicose disease of the lower
      extremities complicated by trophic ulcers].
AB  - The principles of preoperative management of patients with varicosity complicated
      by trophic ulcers are discussed. The main type of treatment is surgery including
      subfascial ligation of the perforating veins of the thigh, leg, and
      foot+phlebectomy after Troyanov-Trendelenburg-Bebcock-Narath. The author suggests
      or modifies approaches to the perforating veins. The basis of preoperative
      management is formed of measures causing a general effect on the organism
      (lysozymo--and immunoglobulinotherapy, stimulation of regeneration by means of
      zinc sulphate, transfusion of albumins, etc.), local treatment (cleansing of the
      ulcer by low-frequency ultrasound, and with immobilized enzymes), and measures
      for improving microcirculation (magnesium preparations, disaggregants,
      ultrasound). Complex treatment based on subfascial ligation of perforating veins
      and removal of varicose superficial veins led to stable healing of ulcers in
      98.2% of patients.

PMID- 8158943
TI  - [Intravascular thrombolytic therapy in the treatment of acute thrombophlebitis of
      the lower extremities and pelvis (Report 1)].
AB  - A new method of thrombolytic therapy is described and substantiated. It consists
      in percutaneous catheterization of the popliteal vein with a system of paired
      catheters with the inner one being advanced during infusion of the thrombolytics
      in the thickness of the thrombus along the length of the proximal segments of the
      main vein. Phlebographic control is accomplished through the outer, short
      catheter. The preparations of streptokinase awelysin and celiase were used. The
      new method of treatment was applied in 27 cases. Comparison with groups of
      patients treated by other methods of systemic and regional thrombolytic therapy
      showed that the efficacy of the suggested method was higher. Good late results
      were found in 72% of patients of the main group. A necessary condition of the
      applied method is prevention of thromboembolism of the pulmonary arteries by
      temporary implantation of a cava-filter into the inferior vena cava.

PMID- 8158944
TI  - [Experience with the use of clopheline in geriatric anesthesiology].
AB  - The new aspects of the use of the central adrenopositive agent clopheline as a
      component of combined endotracheal anesthesia were studied. In distinction to the
      recommendation of some authors, clopheline was used in the preanesthesia period
      in an average dose of 2.5-3.0 mcg/kg (in debilitated patients in a dose of 1.8
      2.2 mcg/kg). The authors examined 86 patients 60 to 85 years of age during
      planned and emergency operations on the biliary tract. All of them suffered from
      arterial hypertension: 70% had three and more concomitant diseases; 20% of
      patients were related to IB category of anesthesiological risk, 65% to IIB
      category, and 15% to IIIB category. The condition of peripheral and central
      hemodynamics, the stress index, and the excretion of the free forms of
      catecholamines (CA), their precursors, and metabolites were studied. During
      anesthesia with the use of clopheline by the suggested method, moderate
      activation of the sympathoadrenal system within the stress-norm occurs. During
      anesthesia as well as in the postanesthesia period the mechanisms of
      autoregulation, which contribute to rapid return of the activity of the
      sympathoadrenal system to the initial level and the control of the relationship
      of the synthesis and inactivation of CA, their precursors, and metabolites, are
      maintained. The method made it possible to reduce the doses of barbiturates to 2
      3 mg/kg, and the doses of fentanyl by 3-4 times as compared with those in
      neuroleptanesthesia, which, in turn, facilitated rapid regaining of
      consciousness, adequate spontaneous breathing, a good cough reflex, and
      sufficient physical activity immediately after the operation. There were no
      complaints of pain hyperdynamic circulatory shift, trembling of muscles,
      suppressed respiration, and acrocyanosis.

PMID- 8158945
TI  - [Diagnosis and surgical treatment of benign tumors of the lungs].
AB  - Benign tumors of the lungs may be treated only by operation. Operative treatment
      may be rejected in patients with tumors measuring less than 2 cm in diameter and
      absence of clinical signs of their growth. In central benign lung tumors,
      preference must be given to organ-preserving operations: bronchotomy with
      adenomectomy, resection of the bronchus together with the involved part and
      subsequent plastics. In peripheral tumors their enucleation of economical
      resection is advisable. The most promising method is precision laser removal of
      benign lung tumors providing reliable aero- and hemostasis.

PMID- 8158946
TI  - [Is surgical treatment of autoimmune thyroiditis justified? (Lecture)].

PMID- 8158947
TI  - [Classification and terminological designation of Madelung's lipomatosis].
AB  - From experience in the treatment of 18 patients with Madelung's lipomatosis the
      authors suggest a system of designation of the spread of the disease embracing
      the possible localizations of the tumor. The system of recording the spread and
      marked character of the adipose tumors makes it possible to appraise the
      developmental stage of the disease. It is suggested that 4 stages of the disease
      are distinguished. According to the type of growth, two forms of tumors are
      distinguished: nodular and diffuse. Systemic designation and the form of the
      tumor give a more complete idea of the disease and thus allow the optimal tactics
      of surgery to be chosen. Among the numerous terms suggested for the disease, the
      most appropriate, reflecting the essence of the disease is "Madelung's
      lipomatosis". The authors suggest it for unification of the designations of the
      disease and easier literature search and generalization of information on this
      rare disease.

PMID- 8158948
TI  - [Diagnostic and surgical problems in complicated colonic and rectal neoplasms].

PMID- 8158949
TI  - [Use of mechanical suture in anterior resection of the rectum].
AB  - Anterior resection of carcinoma of the rectum was carried out in 129 patients.
      Hand-sutured anastomoses were formed in 73 and stapled anastomoses in 56
      patients. There were 7 leaks after sutured anastomoses (9.6%) and 2 leaks after
      stapled anastomoses (3.57%). No late leaks or strictures were encountered in
      either group. Stapled anastomoses are advantageous for the following reasons:
      they are standardized; they can be created at a lower level than those formed by
      hand sutures, thus avoiding abdominoperineal resection in many patients; the
      incidence of anastomotic leakage is lower; time is saved. The EEA stapler is
      recommended for routine use in anastomoses of the rectum.

PMID- 8158950
TI  - [Retrograde cholangiopancreatography and intraoperative cholangioscopy in
      pancreatic and biliary diseases].

PMID- 8158951
TI  - [Papillotomy in the surgical clinic].

PMID- 8158952
TI  - [Treatment of patients with ureteral calculi].
AB  - Various methods of treatment were introduced to improve the results of management
      of patients with stones in the ureters and early restoration of their working
      capacity. Emergency ureterolithotomy (197 patients) reduced the incidence of
      postoperative complications by 2.4 times and the duration of in-patient treatment
      by 1.8 times. Hermetic sealing of the ureteral suture with glue in
      ureterolithotomy (43 patients) led to airtightness of the suture in 93.0% of
      cases. Needle reflexotherapy relieved an attack of renal colics in 94% of
      patients. After general multicomponent vibration (71 patients) and sonic
      stimulation (216 patients) the stones were discharged in 80.3 and 93.1% of
      patients, respectively. The application of organizational measures (creation of a
      city center of emergency urological service) and introduction of new methods for
      treatment of ureteral stones reduced the terms of rehabilitation of patients by
      1.8 times, the economical effect in this case came to 392,3 rubles per each
      patient.

PMID- 8158953
TI  - [Role of local lymphatic stimulation in the prevention of early complications
      after stomach surgeries].
AB  - Experiments were conducted on 120 albino rats and 16 dogs with the use of
      scanning and electron microscopy as well as the radionuclide method of
      microcirculation study to substantiate the method of regional lymphostimulation
      after operations on the stomach for the prevention of early postoperative
      complications. Some lymphagogues (lidase, heparin, procaine hydrochloride) were
      infused in the early postoperative period through a catheter introduced into the
      hepatoduodenal ligament. This zone is represented by a large group of lymph nodes
      receiving lymph from the stomach and the adjacent organs and the intercellular
      space of the hepatoduodenal ligament. The study showed that lymphostimulation
      improves the circulation of lymph and blood which are disturbed as the result of
      the operation and improves the local homeokinesis in the wall of the stomach
      after its resection and vagotomy. Lymphostimulation increases the resorption and
      transport activity of the lymphatic system and improves drainage of the edema
      fluid and the products of disturbed metabolism from the interstitium of the
      gastric mucosa. The results of using the method of regional lymphostimulation in
      441 patients after various operations on the stomach for peptic ulcer showed the
      possibility of reducing the number of early postoperative complications, such as
      inadequacy of the sutures of the gastroduodeno--entero--anastomosis,
      anastomositis, infectious-inflammatory complications, and others.

PMID- 8158954
TI  - [Hemostasis in deep injuries of the liver].
AB  - Experimental and clinical substantiation of the use of an original alloyed staple
      with shape memory allowed it to be recommended for closure of deep wounds of the
      liver when all other known methods and constructions are ineffective. The staple
      causes a lesser zone of necrosis than that produced by catgut in closure of a
      similar wound, and it can be removed with no loss of blood. Consequently, its
      application is a method of today, causes little injury, and is promising.

PMID- 8158955
TI  - [Device for collecting tissue specimens].
AB  - The authors suggested and constructed a device for collecting biopsy specimens
      with a smooth surface and edges. The cutting element was of the type of a razor
      which was installed on a rod parallel to the body of the device; the body and the
      rod were fitted into bands allowing longitudinal movement. A tube was attached in
      the body, and a perforated plate was installed at the end of the tube. The last
      named was connected to a nozzle for connection with the vacuum source. The
      working end of the body had a cutting edge.

PMID- 8158956
TI  - [Mayo-Robson modification of jejunostomy].

PMID- 8158957
TI  - [Ultrasound-guided target puncture of pathologic masses of the abdominal cavity].

PMID- 8158958
TI  - [Current problems in the diagnosis of colorectal neoplasms].

PMID- 8158959
TI  - [Torsion of the omental appendages of the colon].

PMID- 8158960
TI  - [Internal appendicular-intestinal fistula as complication of acute appendicitis].

PMID- 8158961
TI  - [Microsurgical allotransplantation of fetal bone on a vascular peduncle:
      immunological aspects].
AB  - The authors studied the immunological profile of three patients after
      transplantation of bone allobrephotransplants with their microsurgical
      revascularization in the recipient zone. A reaction of rejection of the
      transplanted brephobone did not occur in any of the three cases. In
      transplantation of a complex brephobone the soft tissues overlying it, rejection
      of the soft tissues was encountered but there were no signs of bone rejection.
      The data of immunological monitoring correlate with the results of the
      clinicolaboratory and histological studies.

PMID- 8158962
TI  - Recommendations for the health monitoring of mouse, rat, hamster, guineapig and
      rabbit breeding colonies. Report of the Federation of European Laboratory Animal
      Science Associations (FELASA) Working Group on Animal Health accepted by the
      FELASA Board of Management November 1992.

PMID- 8158963
TI  - Guidelines for the welfare of animals in rodent protection tests. A report from
      the Rodent Protection Test Working Party.
AB  - The rodent protection test (RPT) is used in antimicrobial research to confirm the
      in vivo efficacy of novel antibacterial, antiviral and antifungal agents. The RPT
      may involve lethal infection and thus has the potential to cause significant
      suffering. These Guidelines recommend refinements to the RPT which reduce animal
      use to a minimum and suggest cardinal clinical signs which act as predictors of
      lethality. Early recognition of these signs is imperative to minimize suffering,
      allow identification of humane end points and permit timely euthanasia.
      Constructive suggestions for the improvement of these Guidelines are welcomed.

PMID- 8158964
TI  - Comparison of indirect haemagglutination test, gel-diffusion precipitin test, and
      enzyme-linked immunosorbent assay for detection of serum antibodies to
      Pasteurella multocida in naturally and experimentally infected rabbits.
AB  - Enzyme-linked immunosorbent assay (ELISA), gel-diffusion precipitin test (GDPT),
      and indirect haemagglutination test (IHAT) were evaluated for the detection of
      antibodies to Pasteurella multocida in both naturally and experimentally infected
      rabbits. A total of 285 rabbit serum samples from 7 rabbit colonies were tested
      by ELISA, GDPT, and IHAT, and nasal cultures were taken coincidentally to use as
      the standard in the serological tests. There was better correlation (98.0%)
      between the results of ELISA and positive nasal culture than between the GDPT
      (86.3%) or IHAT (23.5%) and positive nasal culture. In addition, ELISA and GDPT
      were positive in 26 (11.1%) and 21 (9.0%) of 234 serum samples from nasal culture
      negative rabbits, respectively. In experimentally infected rabbits, antibodies
      detected by the ELISA and GDPT began to rise one to 3 weeks post-inoculation.
      IHAT did not detect antibodies. These results are discussed in terms of value to
      serodiagnosis of rabbit pasteurellosis.

PMID- 8158965
TI  - Diagnosis of Kilham rat virus using PCR.
AB  - The exclusive use of serology, namely immunofluorescent antibody (IFA), for the
      diagnosis of rodent parvovirus infection is limited to detecting IgG antibodies
      which develop some time after the appearance of clinical symptoms, whilst
      conventional viral isolation, using tissue culture, is both expensive and time
      consuming. Polymerase chain reaction (PCR) as a diagnostic method has the
      potential to overcome these problems. However, it requires detailed knowledge of
      the genetic code of the target organism and careful selection of the primers
      used. This paper describes preliminary findings in a PCR assay which detected
      Kilham rat virus, minute virus of mice and Toolan's H1 virus.

PMID- 8158966
TI  - Detection of rodent RNA viruses by polymerase chain reaction.

PMID- 8158967
TI  - Changes with age of mammary glands in male and female soft-furred rat, Millardia
      meltada, in relation to prolactin and testosterone.
AB  - The soft-furred rat, millardia (Millardia meltada), is characterized by the
      development of androgen-dependent mammary tumours only in males. The age-related
      changes of the activities of thymidylate synthetase (TS) and thymidine kinase
      (TK), which contribute to DNA synthesis through de novo and salvage pathways,
      respectively, and structure in the mammary glands were studied in both males and
      females of this species between 5-28 months of age. While TK activity had no
      relation to age, TS activity decreased with age in males. In the females, TK
      activity increased with age, but not TS activity. These enzyme activities were
      generally higher in females than in males. The mammary glands of both sexes
      consisted of fine ducts with small end-buds and the glands of males contained
      mostly black pigments at any age examined. In either males or females, serum
      levels of prolactin and testosterone related little with age, DNA synthesizing
      enzyme activities or structure of the mammary glands. Furthermore, elevation by
      pituitary grafting of circulating prolactin affected neither DNA synthesizing
      enzyme activities nor structure of mammary glands in both sexes. The histological
      structures of adrenal, testis, ovary, ventral prostate and uterus of millardia
      were essentially similar to those of mice or rats.

PMID- 8158968
TI  - Pregnancy dependence of mammary tumours in DDD mice congenic for Mtv-2, DDD/1-Mtv
      2/Mtv-2.
AB  - Mammary tumours developed in 110 (95.7%) of 115 DDD/1-Mtv-2/Mtv-2 (DDD/1-Mtv-2)
      and 24 (47.1%) of 51 DDD/1fDDD/1-Mtv-2 (DDD/1fMtv-2) force-bred female mice
      during a one-year period. The mean tumour age +/- SE was 220 +/- 7 and 269 +/- 7
      days, respectively. These tumours were examined for responsiveness to pregnancies
      by comparing their growth after transplantation between virgin and breeding
      recipients. Of 73 tumours from DDD/1-Mtv-2 mice, 9 (12%) were completely
      pregnancy-dependent (CPD), 3 (4%) pregnancy-dependent (PD), 9 (12%) pregnancy
      responsive (PR), and 52 (71%) pregnancy-independent (PI), and of 25 tumours from
      DDD/1fMtv-2 mice, one (4%) was CPD, one (4%) PR, and 23 (92%) PI. Although most
      tumours were heterogeneous in morphology and there was no clear relation between
      morphology and PD properties, most CPD tumours were type P and considered to be
      connected with mammary plaques. When 9 CPD tumours from DDD/1-Mtv-2 mice were
      serially transplanted in breeders, 6, 2 and one progressed to lose pregnancy
      dependence within 3, 8 and 18 generations, respectively. DDD/1-Mtv-2 mice will
      provide a model for studies on progression of mammary tumours from hormone
      dependent to autonomous states.

PMID- 8158969
TI  - Behaviour of nucleolar organizer regions in the different Wistar rat liver lobes.
AB  - The area and number of silver-nucleolar organizer regions (Ag-NORs) in the
      hepatic lobes were determined in 3 male Wistar rats. There was a statistically
      significant increase in the percentage of Ag-NORs per nucleus in the right
      lateral and caudate lobe in relation to the left lateral and middle lobes. The
      area and number of Ag-NORs are greater in the caudate and right lateral lobes in
      relation to the left lateral and middle lobes. Since the Ag-NOR is a parameter
      which indicates hepatocytic protein synthesis, the different activity which
      corresponds to each lobe of the rat's liver makes it possible to assume that
      there is a functional heterogeneity which should be considered in the study of
      the hepatic regeneration according to the type of partial hepatectomy carried
      out.

PMID- 8158970
TI  - Maternal age, reproduction and chromosomal aberrations in Wistar derived rats.
AB  - The fertility of rats ranges from one to 18 months. In standard teratogenicity
      testing young, mature females are used which may not reflect the situation in
      women above 35 years old. Reproduction among different age groups of Wistar ats
      (strain Chbb: THOM) was compared at 3, 6, 9, 12, 15 and 18 months. At least 20
      virgin females were inseminated per age group. The copulation rate did not differ
      between the groups. From the maternal age of 12 months, the pregnancy rate was
      significantly decreased, from the age of 9 months, the litter values were
      significantly lowered and the resorption rates were increased. Maternal age did
      not influence the incidence of fetal variations and malformations. Additionally,
      the chromosomal aberration rate in the bone marrow was evaluated in male and
      female rats. Twelve animals of each sex were scheduled per group, and studied at
      the age of 1, 3, 6, 12, 15, 18, 21 or 24 months. In males, the aberration rate
      increased continuously from 0.18 through 3%, while in females the increase
      continued from 0.33 to 2.29% at 15 months old when a plateau was reached. When
      testing new compounds for embryotoxicity or genotoxicity in female rats, the
      animals should be of comparable age to man in order to avoid a misinterpretation
      of spontaneous abnormalities. From these studies, however, it was concluded that
      the use of higher age groups of female rats in teratogenicity studies would not
      improve the risk assessment.

PMID- 8158971
TI  - Glycated albumin: a marker of glycaemic status in rats with experimental
      diabetes.
AB  - Monoclonal antibodies that specifically recognize non-enzymatically glycated
      epitopes residing in albumin were used to measure levels of glycated albumin in
      the plasma of control and streptozotocin diabetic rats. Standard or sample was
      incubated with monoclonal antibody immobilized onto preactivated tubes, and
      binding was detected with enzyme-conjugated polyclonal antibody to rat albumin
      and substrate. Rat glycated albumin exhibited a linear dose response in the
      assay, and plasma samples contained between 30-100 micrograms/50 microliters.
      Levels were significantly increased in diabetic compared with control rats, and
      correlated positively and significantly with mean blood glucose concentrations
      measured in the fasting and fed states. The results indicate that glycated
      albumin levels measured by immunoassay reflect recent integrated glycaemia and
      provide and objective index of glycaemic status in the rat experimental model of
      diabetes.

PMID- 8158972
TI  - The use of etorphine/methotrimeprazine and midazolam as an anaesthetic technique
      in laboratory rats and mice.
AB  - The results of a preliminary evaluation of etorphine/methotrimeprazine ('Small
      Animal Immobilon') and midazolam in rats and mice are reported, and this regimen
      is compared to fentanyl/fluanisone/midazolam in mice. In rats, a surgical plane
      of anaesthesia with good muscle relaxation was produced, but blood gas analysis
      showed the presence of severe hypoxia, hypercapnia and acidosis. In mice
      etorphine/methotrimeprazine/midazolam and fentanyl/fluanisone/midazolam produced
      adequate anaesthesia, but blood gas analysis showed severe respiratory depression
      with both regimens. Since etorphine/methotrimeprazine/midazolam produced severe
      respiratory depression in rats and mice it is suggested that this regimen is used
      with caution. Administration of supplemental oxygen would seem advisable when
      using either etorphine/methotrimeprazine/midazolam or
      fentanyl/fluanisone/midazolam in rats and mice.

PMID- 8158973
TI  - A new method of faeces collection in the pig.
AB  - A new faeces collection method for pigs has been developed which allows
      collection of faeces into a plastic bag. This new method greatly reduces faecal
      losses and thereby permits virtually complete collection of faecal material. The
      method can be applied easily and causes less discomfort to the animals than
      previous methods.

PMID- 8158974
TI  - Calcified foci at the junction between adrenal cortex and medulla of rhesus
      monkeys.
AB  - The occurrence of calcified foci at the junction of adrenal medulla and cortex in
      monkeys obtained from toxicity studies during a 10-year period is reported. The
      survey included reinvestigated adrenal samples from 274 male and 270 female
      rhesus monkeys and 52 male and 52 female cynomolgus monkeys. The incidence of
      calcified foci was 46% in male and 45% in female rhesus monkeys, and 6% in male
      cynomolgus monkeys, while their females did not show the lesion. In male rhesus
      monkeys, the mean number of foci was 4 for both glands, in females, 2 for the
      right and 4 for the left one. Initial stages indicated that the lesions develop
      possibly from focal apoptosis of medulla cells followed by a dystrophic
      mineralization. No correlation was observed concerning dose groups, test article,
      study length, testing facility, origin of monkeys, their sex, age, diet or final
      body weight. The foci of mineralization were dystrophic, species-specific in the
      rhesus monkey and possibly related to stress. The location of the foci at the
      cortico-medullary junction, precisely the location of the remnants of the fetal
      zone, may indicate their origin from this zone.

PMID- 8158975
TI  - Bilateral complex odontoma in a Swiss (CD-1) male mouse.
AB  - The present report describes the morphological features of a spontaneous,
      bilateral, complex odontoma of the incisor teeth in an 87-week-old male Swiss
      mouse (Crl: CD-1(ICR)BR). This report constitutes the second report of an
      odontogenic tumour in a Swiss mouse and the first describing a bilateral complex
      odontoma in this strain of mouse. The report emphasizes the importance of
      thoroughly examining the oral cavity for dental tumours.

PMID- 8158976
TI  - Research-oriented genetic management of nonhuman primate colonies.
AB  - Genetic management is an important component of the general management of
      nonhuman primate colonies. However, standard genetic management techniques were
      developed primarily to address the goals of population conservation, particularly
      in zoo situations. The special needs of colonies that produce animals for
      biomedical research have not previously been fully addressed and the great
      potential of genetic management in the research environment remains to be
      realized. A research-oriented genetic management approach balances long-term
      breeding goals and current and future experimental needs, yielding a
      comprehensive overall colony management program. Pedigree information, genetic
      markers (e.g., serum proteins, red blood cell enzymes, restriction fragment
      length polymorphisms, and single-locus microsatellites), and quantitative traits
      (e.g., routinely gathered clinical chemical values, weights, and blood pressures)
      can be used alone or in combination to estimate genetic variability in the colony
      and to characterize animals for experimentally relevant traits. The statistical
      power of experiments using nonhuman primates can be improved when animals are
      selected on the basis of their genetic values or genotypes for experimentally
      relevant traits because the quantified genetic variation among subjects can then
      be minimized. The incorporation of experimental needs into the overall genetic
      management plans for captive breeding colonies helps ensure the long-term
      viability of colonies for meeting the demands of both breeding and research.

PMID- 8158977
TI  - Infrequent shedding and transmission of herpesvirus simiae from seropositive
      macaques.
AB  - The epizootiologic properties of Herpesvirus simiae (B virus) were studied in
      singly housed macaques (Macaca mulatta and M. fascicularis) in a biomedical
      vivarium to determine whether commonly encountered environments and procedures
      such as quarantine, breeding, Caesarean section, parturition, and social stress
      induced virus shedding and transmission. Macaques were tested serologically and
      for infectious virus. Oral, conjunctival, and vaginal swab samples were obtained
      repeatedly. Virus excretion was not detected during a 7-week quarantine of 32
      newly acquired, singly housed animals tested every other week for 6 weeks, and
      none of 19 seronegative animals from this group seroconverted during 7 weeks in
      quarantine. No virus shedding was detected in 16 seropositive animals tested
      weekly for 3 weeks after Caesarean section or normal parturition or in 11
      seropositive animals following introduction of new males to animals rooms. One
      animal seroconverted after repeated breeding of seropositive animals to
      seronegative partners. Fifty-three singly housed offspring remained seronegative
      for up to 10 years, even if born to seropositive dams, and only 1 of 86 singly
      housed animals less than 7 years old was seropositive. These results suggest that
      shedding of B virus from seropositive macaques is uncommon, when subjected to
      common laboratory procedures or environments, and that transmission is rare in
      singly housed animals. These results may be useful in establishing B virus-free
      colonies of macaques.

PMID- 8158978
TI  - Disseminated B virus infection in a cynomolgus monkey.
AB  - A cynomolgus monkey (Macaca fascicularis) was euthanatized 1 week following
      dystocia because of severe peritonitis. Histologic examination revealed lesions
      characteristic of herpesvirus infection in lungs, liver, spleen, bone marrow,
      uterus, and adrenal gland, and on the serosal surface of intestines, pancreas,
      and reproductive tract. Immunohistochemical studies on liver and lungs revealed
      Herpes B-like antigens in the lesions. B virus was isolated from serum. As
      systemic B-virus infection was not diagnosed before death of the monkey, these
      findings underscore the need for universal precautions when handling blood,
      fluids, or tissues from macaques.

PMID- 8158979
TI  - Fatal spontaneous pneumocystosis in nude rats.
AB  - Spontaneously generated fatal pneumocystosis was found in a congenitally athymic
      nude (rnu/rnu) rat colony. Severe pulmonary pneumocystosis was seen in rnu/rnu
      rats, and 10(7) to 10(8) cysts per lung were detected. No histologic changes were
      seen nor were Pneumocystis carinii organisms detected in heterozygous rnu/+ rats.
      Indirect immunofluorescence revealed strong reactivity in the sera from rnu/+
      rats with rat-P. carinii cysts (originated from Wistar strain), compared with
      mouse- or human P. carinii cysts. The cysts isolated from rnu/rnu rats reacted
      strongly with antirat-P. carinii rat serum in comparison with antimouse-P.
      carinii rabbit serum and serum from a human with pneumocystosis. Immunoblotting
      studies using rat-P. carinii antigen showed that 116-kDa antigen reacted with the
      antirat-P. carinii serum and sera from rnu/+ rats but not with the antimouse-P.
      carinii serum and the serum from a human with pneumocystosis, whereas 52-kDa
      antigens of rat-P. carinii were recognized by all the anti-P. carinii sera
      tested. On the basis of our findings, the outbreak was caused by the P. carinii
      indigenous to the rat.

PMID- 8158980
TI  - Cataracts in a laboratory colony of ferrets.
AB  - Cataracts were found by use of slit-lamp biomicroscopy in two genetically
      unrelated ferret populations (A and B). When they were initially examined at the
      age of 11 to 12 months, 34 of 73 ferrets (46.6%) in population A had lens
      opacities, which could be categorized into one of three groups. Group-1 ferrets
      (n = 25) manifested a continuum of lens changes ranging from fine, multifocal,
      punctate opacification of the superficial posterior lens cortex (n = 3), to
      changes in both the anterior and posterior cortex (n = 13), to immature (n = 1),
      or mature/hypermature cataracts (n = 8). Group-2 ferrets (n = 7) had bilateral
      microphthalmia and cataracts. Group-3 ferrets (n = 2) had minor lens changes
      involving the nucleus or cortex that were not typical of either group 1 or 2. By
      the age of 18 months, 41 of the remaining 42 animals in population A had
      developed fine, multifocal, punctate opacities of the posterior cortex. In group
      1 animals, histologic changes in the lens ranged from several 80 x 40-microns,
      punctate, spheroidal lesions in the posterior cortex, to posterior migration of
      the lens epithelium, Morganian granules, and a complete mature/hypermature
      cataract. One group-2 ferret had microphthalmia, filling of the lens capsule with
      a cell-poor, periodic acid-Schiff stain-positive membranous material, and retinal
      detachment. Population B consisted of 15 adult and 47 6-month-old juvenile
      ferrets. Eleven adults had multifocal, fine, punctate, posterior cortical
      opacities, and one adult had a nuclear cataract.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158981
TI  - Changes in platelet-activating factor, catecholamine, and serotonin
      concentrations in brain, cerebrospinal fluid, and plasma of pichinde virus
      infected guinea pigs.
AB  - Brain concentrations of platelet-activating factor (PAF), catecholamines, and
      serotonin were measured in control and Pichinde virus-infected strain 13 guinea
      pigs on postinoculation day (PID) 12. After virus inoculation, PAF concentrations
      increased 81% in cerebrum, 147% in diencephalon-brain stem, and 110% in
      cerebellum from baseline values of 2.6 +/- 0.3, 4.3 +/- 0.2, and 6.1 +/- 0.5
      (ng/g wet tissue), respectively. Dopamine concentrations in the infected cerebrum
      and diencephalon-brain stem increased significantly, whereas norepinephrine
      concentration increased only in cerebrum. However, serotonin concentrations in
      all three regions of infected brain decreased significantly as compared with
      control values. There were no significant changes in epinephrine concentrations
      of infected brain. Norepinephrine and epinephrine concentrations in plasma and
      cerebrospinal fluid on PID 7 and 12 increased significantly as compared with
      control values, while plasma dopamine concentration increased significantly on
      PID 7. Increased brain PAF, dopamine, and and norepinephrine concentrations with
      decreased brain serotonin concentrations may mediate the hyperactivity of the
      hypothalamic-pituitary-adrenal axis and involve some unknown pathophysiologic
      processes of arenaviral infection. Furthermore, increased plasma catecholamine
      concentrations are associated with stress and may be partially responsible for
      the development of cardiovascular dysfunction and pulmonary edema during this
      viral disease.

PMID- 8158982
TI  - The gerbil, hamster, and guinea pig as rodent models for hyperlipidemia.
AB  - The purpose of this study was to compare the effects of a hyperlipidemic diet on
      three different rodent models to evaluate them on how their responses simulate
      human serum lipid diseases. Forty hamsters, 40 gerbils, and 20 guinea pigs were
      given either a chow diet or a modified high-fat, high-cholesterol diet (HF/HC)
      for 7 days. Food was withheld from half of the animals on each diet for 12 hours
      prior to collecting the blood for analysis of total cholesterol and triglyceride
      concentration. In all species, HF/HC feeding resulted in at least a 370% increase
      in total cholesterol concentration. Withholding food significantly decreased
      total cholesterol concentration in hamsters and gerbils fed HF/HC but had no
      effect on animals fed chow diet. Triglyceride concentrations were increased by
      the HF/HC in the hamster and the gerbil. As with total cholesterol, triglyceride
      concentration was decreased after food was withheld in these two animal groups.
      We suggest that the guinea pig is the most appropriate model for studying
      hypercholesterolemia because of its moderate plasma cholesterol response and
      normal triglyceride response to a HF/HC. We also suggest that the hamster is a
      good model for studying hypertriglyceridemia since increased serum triglyceride
      concentrations can be easily maintained on a HF/HC.

PMID- 8158983
TI  - A comparison of euthanasia methods in rats, using carbon dioxide in prefilled and
      fixed flow rate filled chambers.
AB  - The two methods (prefilled and fixed flow rate filled chambers) recommended in
      the 1993 AVMA Euthanasia Panel report for using carbon dioxide to euthanatize
      rats were evaluated in terms of their effect on behavior and selected blood gas
      values. Responses were videotaped during exposure to > or = 90% carbon dioxide in
      a prefilled chamber or a gradually filled chamber, using a fixed flow rate of 20%
      chamber volume/min. Arterial blood samples were taken to determine partial
      pressure of oxygen, partial pressure of carbon dioxide, pH, and oxygen saturation
      prior to entering the chamber and at time points determined by rats' responses to
      carbon dioxide. Rats showed similar reactions when exposed to carbon dioxide by
      either method. Significant differences in mean time for each response to occur
      were seen between euthanasia methods. Maintaining a near atmospheric oxygen
      chamber concentration by using a 75% CO2: 20% O2: 5% N2 gas mixture to gradually
      fill the chamber did not change rats' reactions upon exposure. Significant
      differences were found between pre-exposure values and values from samples
      obtained when rats became immobile after entering the prefilled chamber. Partial
      pressure of carbon dioxide significantly increased, and pH and percent oxygen
      saturation significantly decreased from pre-exposure values in all samples
      obtained after rats entered the gradually filled chamber. Partial pressure of
      oxygen in these rats was greater than or equal to pre-exposure levels in all
      samples. Rats appeared sedated because of the anesthetic effects of carbon
      dioxide when immobility was observed. Distress was not observed in the rats when
      either method of euthanasia was used.

PMID- 8158984
TI  - Echocardiographically detected myocardial infarction in the mouse.
AB  - The ability to obtain high-quality echocardiographic images of the heart in a
      small mammal such as the mouse would enable investigators to noninvasively and
      serially assess cardiac function and identify focal lesions. We recently had the
      opportunity to perform noninvasive high-frequency M-mode echocardiography in a
      mouse that had a focal area of left ventricular hypokinesis involving the ventral
      wall. Postmortem histologic examination revealed lateral and ventrolateral wall
      infarction with fibrotic replacement of the ventricular wall and reactive
      hypertrophy of surrounding myocytes in noninfarcted zones. To our knowledge, this
      is the first reported case of noninvasive echocardiography identification of a
      myocardial infarction in the mouse and further high-lights the potential utility
      of this technique.

PMID- 8158985
TI  - Anatomic features and radiographic observations of gastric emptying and small
      intestinal motility in the rat.
AB  - This study presents the first report of the identification of anatomic structures
      on survey radiographs of the abdomen of the rat, along with detailed barium
      contrast studies of the gastrointestinal tract in normal rats. The rats (49 to
      112 days old) were chemically restrained with a combination of 0.71 mg ketamine
      hydrochloride/g of body weight and 0.5 mg of acetylpromazine maleate injected
      intramuscularly. Following sedation, a 36% (wt/vol) micropulverized barium
      sulfate suspension was administered via a stomach tube at a dose of 0.02 ml/g of
      body weight. The radiographic features of the gastrointestinal tract were
      enhanced after coating of the mucosal surfaces with the high-density barium
      suspension. Internal structures of the stomach and mucosal surfaces of the
      intestine were clearly identified. The barium contrast study was used to
      establish gastrointestinal transit times. The mean gastric emptying time was 11
      +/- 4.27 (SEM) min and mean intestinal transit time was 5 +/- 0.75 (SEM) h. Image
      intensification fluoroscopy was used to observe patterns of small intestinal
      motility and to establish small intestinal contraction rates. Prominent cluster
      of circular contractions were primarily observed in the jejunum, and wave-type
      peristalsis was primarily observed in the duodenum. Isolated circular
      contractions and weak segmentation patterns were observed in the ileum. The mean
      contraction rate per minute was observed to be 14 +/- 2.12 (SEM) in the jejunum.
      We propose that under the conditions of the current study, radiographic
      investigation of gastrointestinal function in rats is a feasible and inexpensive
      procedure.

PMID- 8158986
TI  - Use of a single injection solute-clearance method for determination of glomerular
      filtration rate and effective renal plasma flow in chickens.
AB  - A single-injection clearance method for determining glomerular filtration rate
      (GFR) and effective renal plasma flow (ERPF) in chickens was compared with the
      continuous-infusion method. Male and female White Leghorn chickens were
      anesthetized, and catheters were placed in both brachial veins and over both
      ureteral openings. A single-bolus injection of 3H-inulin and 14C-para
      aminohippuric acid was given at a dose of 1.0 microCi of each solute per kg of
      body weight and nine blood samples were obtained over 60 min. After the last
      sample was taken, the birds were given a bolus injection of 1 microCi of 3H
      inulin/kg and 1 microCi of 14C-para-aminohippuric acid/kg, followed by a constant
      infusion of 0.1 microCi of each solute/min at a rate of 0.1 ml.kg-1 x h-1.
      Following a 45-min stabilization period, three continuous urine collections were
      performed. A blood sample was obtained at the midpoint of each urine collection.
      The GFR and ERPF determined by the single-injection method (3.12 +/- 0.43 and
      22.81 +/- 3.48 ml.min-1 x kg-1, respectively) were comparable to values for the
      continuous-infusion method (2.81 +/- 0.35 and 22.88 +/- 4.03 ml.min-1 x kg-1,
      respectively). Both GFR and ERPF determined by the single-injection method
      correlated with GFR and ERPF determined by the continuous-infusion method. This
      single injection method provides a rapid, accurate method for determining GFR and
      ERPF in chickens and eliminates the need for collection of urine.

PMID- 8158987
TI  - Estrus detection by using vaginal cytologic examination in miniature swine.
AB  - Vaginal smears were obtained from four Yucatan miniature swine daily for 69 days
      and stained with hematologic stain. Epithelial cells were categorized as
      superficial, large intermediate, small intermediate, or parabasal. Leukocytes
      were also quantitated. External signs of estrus were recorded, including
      swelling, discharge, restlessness, or vocalization. Mean age of three of the
      swine was 147 days at the beginning of the study. The fourth pig was 317 days
      old. The three younger swine had their first observed estrus at the age of 178
      days (range, 167 to 196 days). Mean cycle length was 17 to 21 days. The moving
      mean leukocyte count (i.e., each value was averaged with the values for the
      previous day and the following day) always exceeded the epithelial cell count
      (regardless of type), except during the 3 to 4 days when the pigs exhibited
      external signs of estrus. Further, epithelial cells were at their peak during
      estrus, decreasing markedly during diestrus, and increasing again during
      proestrus. The combined superficial plus large intermediate cell counts were
      significantly higher during estrus than during diestrus or proestrus. We conclude
      that daily vaginal smears can be used to determine the stage of estrus in Yucatan
      pigs.

PMID- 8158988
TI  - Identification of inbred rat strains by using DNA fingerprinting method.
AB  - DNA fingerprinting method was applied to identify inbred strains of laboratory
      rats. By Southern blot hybridization with core sequence of minisatellite DNA as a
      probe, typical hypervariable patterns of DNA fingerprint were obtained in inbred
      rat strains. The patterns were completely different among 15 rat strains
      examined, and the patterns of the DNA fingerprint of samples obtained from the
      same strain were completely identical. The patterns of the DNA fingerprint of two
      substrains derived from the same strain were identical, indicating relative
      stability of the patterns over a large number of generations. Therefore, we
      concluded that the DNA fingerprinting method was useful for the identification of
      inbred strains in genetic monitoring of laboratory rats.

PMID- 8158989
TI  - Anesthetic potency and cardiopulmonary effects of enflurane, halothane, and
      isoflurane in goats.
AB  - Anesthetic requirements, as defined by the minimum alveolar anesthetic
      concentration (MAC) that prevents gross, purposeful movement in 50% of animals,
      have not been determined in goats. Therefore, we determined anesthetic potency of
      enflurane (N = 6), halothane (N = 8), and isoflurane (N = 7) in goats by using
      the tail clamp and dew-claw clamp as the noxious stimuli and then measured the
      cardiovascular and respiratory effects of these agents. The MAC was 2.0 +/- 0.4%,
      1.3 +/- 0.1%, and 1.5 +/- 0.3% (mean +/- SD) for enflurane, halothane, and
      isoflurane, respectively. At 1 MAC, when ventilation was changed from controlled
      to spontaneous, blood pressure decreased in goats anesthetized with isoflurane
      (98 +/- 17 to 78 +/- 13 mm Hg) and halothane (95 +/- 10 to 83 +/- 14 mm Hg) but
      did not significantly change in goats anesthetized with enflurane; heart rate
      increased in goats anesthetized with halothane (117 +/- 12 to 127 +/- 10
      beats/min) but was not significantly different in goats anesthetized with
      enflurane or isoflurane; and cardiac output increased in goats anesthetized with
      enflurane (5.70 +/- 1.23 to 7.05 +/- 2.02 liters/min) and halothane (6.14 +/-
      0.94 to 7.91 +/- 2.45 liters/min) but not with isoflurane. During spontaneous
      breathing, respiratory depression was manifested by apnea in two animals and an
      elevated PaCO2: 57 +/- 15 mm Hg, 55 +/- 13 mm Hg, and 59 +/- 14 mm Hg,
      respectively, for enflurane, halothane, and isoflurane. Minute ventilation during
      spontaneous breathing was approximately 50% of controlled ventilation for each
      anesthetic agent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158990
TI  - Decontamination of rat embryos and transfer to specific pathogen-free recipients
      for the production of a breeding colony.
AB  - When animals are introduced to a specific pathogen-free (SPF) facility, care must
      be taken to avoid the possibility of disease transmission to the local colony.
      This study investigated the application of a combination of reproductive
      biotechnologies to establish a new disease-free colony of two rat strains,
      DarkAgouti(DA/Pit) and Wistar Furth(WF/Pit), from a stock known to be chronically
      infected with the following pathogens: Mycoplasma pulmonis, Kilham's rat virus,
      sialodacryoadenitis/coronavirus, and reovirus type 3. To eliminate the pathogens
      and optimize the use of animals, superovulation, embryo washing and
      trypsinization, and embryo transfer were used. Donors (DA/Pit and WF/Pit) were
      treated as follows: the mature females were synchronized by subcutaneous (s.c.)
      injection with 40 micrograms luteinizing hormone-releasing hormone agonist/animal
      on day -4. All immature and mature females were induced to superovulate by
      continuous s.c. infusion with a commercial porcine follicle-stimulating hormone
      (FSH) preparation (3.4 or 6.8 mg NIH-FSH-P1 units per day, respectively),
      beginning on the morning of day -2. On the afternoon of day 0, the animals
      received 30 IU human chorionic gonadotropin injected intraperitoneally and mated.
      From a total of 213 ova flushed from the oviducts of 16 programmed donors, 195
      transferrable two-cell embryos were recovered. Two outbred strains of SPF rats,
      Long-Evans (LE) and Wistar (W), were used as recipients. These mature females (LE
      and W) were synchronized by using luteinizing hormone-releasing hormone agonist
      as described and made pseudopregnant by cervical stimulation. Two-cell embryos
      (DA/Pit and WF/Pit) were washed and trypsinized, then transferred to the oviducts
      of the pseudopregnant recipients (LE and W).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8158991
TI  - Diagnostic exercise: pleural and peritoneal nodules in a Fischer 344 rat.

PMID- 8158992
TI  - Diagnostic exercise: ulcerative dermatitis and cellulitis in American toads.

PMID- 8158993
TI  - Diagnostic exercise: intestinal parasitism in an owl monkey.

PMID- 8158994
TI  - Mesocestoides infection in captive olive baboons (Papio cynocephalus anubis).

PMID- 8158995
TI  - Gnathostomiasis in a wild-caught nine-banded armadillo (Dasypus novemcinctus).

PMID- 8158996
TI  - Elimination of sialodacryoadenitis virus from a rat production colony by using
      seropositive breeding animals.

PMID- 8158997
TI  - Control of Pseudomonas aeruginosa infection in mice by chlorine treatment of
      drinking water.

PMID- 8158998
TI  - Sudden death in a pig (Suis scrofa).

PMID- 8158999
TI  - Intermittent hematuria in a colony of Lewis x Brown Norway hybrid rats.

PMID- 8159000
TI  - Effect of environmental factors on the yield of mouse embryos obtained after
      hormone-induced superovulation.

PMID- 8159001
TI  - Effects of T-2 toxin on ovarian activity and some metabolic variables of rabbits.

PMID- 8159002
TI  - Growth pattern and prognosis of gastric cancer invading the subserosa.
AB  - Gastric cancer invading the subserosa with infiltrative growth was classified as
      part of the serosal invasion group and named prognostic serosal invasion positive
      [ps(+)] histologically. We analyzed clinicopathological features and prognosis of
      166 Japanese patients with gastric cancer invading the subserosa, according to
      the growth pattern. All patients were treated in the Department of Surgery II,
      Kyushu University. Patients with infiltrative growth (ss gamma) were younger and
      their tumors were frequently undifferentiated compared to findings in those with
      noninfiltrative growth: expansive (ss alpha) and intermediate growth (ss beta).
      There was no difference in any other clinicopathological characteristic between
      those with infiltrative and noninfiltrative growth tumors. The 10-year survival
      rate was 66.7% for the infiltrative type and 54.2% for the noninfiltrative type,
      with no statistically significant difference. Lymph node metastasis, curative
      resection, and extended lymph node dissection, but not growth pattern, proved to
      be independent prognostic factors, as determined by multivariate analysis. Our
      findings suggest that it is not the growth pattern which affects the prognosis of
      ss cancers. Extensive lymph node dissection should be done when lymph node
      metastasis is present.

PMID- 8159003
TI  - Prognostic significance of in vitro thymidine uptake in patients with colorectal
      carcinoma.
AB  - In 127 patients with colorectal carcinoma, we measured thymidine uptake by tumor
      cells cultured in a semisolid medium and compared the influence of various
      parameters on survival by univariate and multivariate analysis. Fifty-four of the
      127 carcinomas (42.5%) incorporated > 1,000 cpm of tritiated thymidine per
      culture dish and were designated as the high-uptake group, while the other tumors
      (57.5%, 73/127) were designated as the low-uptake group. There was no significant
      correlation between high or low thymidine uptake and most of the
      clinicopathological characteristics of the patients. Patients in the high-uptake
      had a poor prognosis and a 7-year survival rate of 32.6%, which was significantly
      different from the rate of 69.3% in the low-uptake group (P < 0.0005).
      Multivariate analysis showed that thymidine uptake was one of the variables
      strongly associated with survival in our study population. Thus, it is concluded
      that thymidine uptake by tumor cells has a high capacity of predicting prognosis,
      independent of its relationship to other variables. Furthermore, it seems to us
      that thymidine uptake can help in selecting those patients with colorectal
      carcinoma who are most likely to benefit from perioperative adjuvant therapy.

PMID- 8159004
TI  - Adoptive cellular therapy of human breast and colorectal tumor targets using ex
      vivo activated memory T lymphocytes with potentiation by cis
      diamminedichloroplatinum(II).
AB  - Autolymphocyte therapy (ALT) is adoptive cellular therapy of cancer using ex vivo
      activation of autologous peripheral blood lymphocytes (PBL). Memory T cells are
      the principal effector population in ALT, with in vivo activity in patients with
      metastatic renal cell carcinoma (RCC) and melanoma, and ex vivo cytotoxicity
      against autologous tumor targets. However, the noncytolytic lymphocyte portion of
      ex vivo-activated memory T cells (ALT cells) may also contribute as antitumor
      effectors. Pretreatment of murine and human tumor cells ex vivo with
      chemotherapeutic agents can enhance their susceptibility to antitumor lymphocytes
      ex vivo and in vivo. To determine whether cis-diamminedichloroplatinum(II) (DDP)
      could enhance ex vivo antitumor effects of ALT cells by immunomodulation, human
      breast and colorectal carcinoma target cells were derived from both primary and
      metastatic surgical specimens and incubated in complete medium (CM) with DDP or
      in CM alone (control group). Viability of each group was confirmed by trypan blue
      dye exclusion test. ALT cells were prepared from autologous PBL at surgery.
      Primary and metastatic tumor cells from each group were used as targets for ALT
      cells and levels of interferon-gamma (IFN-gamma) release were measured as a
      determination of antitumor effect and recognition. Primary tumor target cells
      incubated in DDP showed enhanced antitumor effects and recognition by autologous
      ALT cells, as measured by the IFN-gamma assay compared to non-DDP-treated
      controls. Metastatic autologous tumor target cells demonstrated less IFN-gamma
      release than did the primary targets, although this was enhanced by pre-treating
      metastatic tumor targets with DDP. ALT cells demonstrated minimal IFN-gamma
      release when incubated with allogeneic tumor targets. These data suggest that
      autotumor recognition of metastatic tumor targets is comparable to that of
      primary lesions following ex vivo pretreatment of metastatic cells with nonlethal
      doses of certain chemotherapeutic agents. DDP may somehow alter the physical
      properties of target cells, rendering them susceptible to immune-mediated attack
      and the combination of ALT and DDP may lead to increased therapeutic efficacy in
      patients with metastatic breast and colon cancer.

PMID- 8159005
TI  - Multidisciplinary treatment of biliary tract cancers.
AB  - Ninety-six patients referred for radiation therapy to Washington University
      affiliated institutions with tumors of the extrahepatic biliary tree form the
      basis of this report. Patients were examined with regard to demographic factors,
      tumor primary site, presenting symptoms, methods of diagnosis, and methods of
      management. The median survival of all 96 patients in this series was 11 months.
      There was no significant difference between patients with gallbladder cancer and
      patients with cancer of the biliary ductal system. There was a statistically
      significant improvement in survival in those patients undergoing resection as
      management or as a component of the management of their tumors (P = 0.02).
      Patients receiving > 4,000 cGy of radiation therapy had an improved survival
      compared to those patients receiving < or = 4,000 cGy of radiation therapy (P =
      0.003). While surgical resection improved survival for those patients undergoing
      removal of all gross tumor, this effect was noted especially in patients with
      gallbladder cancer.

PMID- 8159006
TI  - Interrelationship of prolactin and its receptor in carcinoma of colon and rectum:
      a preliminary report.
AB  - The prolactin receptors (PRLR) were correlated with circulating prolactin and
      various clinicopathologic parameters to investigate its prognostic value in
      patients with colorectal cancer. The prolactin (by radioimmunoassay) and its
      receptors (by radioligand method) were estimated in a total of 71 male patients
      with colorectal cancer enrolled at the Gujarat Cancer and Research Institute,
      Ahmedabad. The patients were followed for a period of 3 years. We have observed
      that 51% colorectal tumors were PRLR+. Significant correlation was not observed
      between presence/absence of PRLR and clinicopathologic variables. Dukes' D
      patients were lost to follow-up after 2-3 months; therefore, the results of
      prognostic significance were analysed only in patients with Dukes' A, B, and C (N
      = 64). Statistically significant difference in overall survival was not observed
      when the patients were subgrouped according to the presence/absence of PRLR and
      according to the cutoff level (i.e., 2%). PRLR+ hyperprolactinemic (Prolactin >
      20.0 ng/ml plasma) patients had better overall survival than that of patients
      with PRLR- hyperprolactinemia, although the difference was statistically
      nonsignificant. However, PRLR- hyperprolactinemia patients had a more
      unfavourable prognosis than that of their counterparts. A similar trend was
      observed in patients with Dukes' B and C disease. Our preliminary study suggests
      an unequivocal finding, that PRLR- with concomitant hyperprolactinemia probably
      characterises a subgroup of patients with aggressive colorectal cancer.

PMID- 8159007
TI  - Role of intraoperative assessment of lymph node metastasis and serosal invasion
      in patients with gastric cancer.
AB  - The clinical diagnoses of nodal status (N) and tumor invasion (T) were performed
      intraoperatively during 1499 consecutive operations for gastric carcinoma and
      compared with subsequent pathologic diagnoses. An accurate macroscopic diagnosis
      of N stage was difficult; overall accuracy was only 56.6%. Intraoperative
      assessment of T stage (particularly of serosal invasion) was correct for 93.2% of
      early stages of the disease with invasion confined to the mucosa or submucosa
      (pT1) when the pathologist assessed the T stage in the resected specimen, for
      95.6% of advanced tumors invading the serosa (pT3), but for tumors of an
      intermediate stage with invasion involving the muscularis propria or the
      subserosa (pT2) in only 41.9% of cases. Macroscopic overestimation occurred in
      58.1% of cases with pT2 tumors, which were characterized by carcinomas in the
      upper third of the stomach, tumors larger than 5 cm, carcinomas of the ulcerating
      type, differentiated adenocarcinomas, tumors invading the subserosa, and those
      accompanied by lymph node metastasis or liver metastasis. The overestimated group
      had a significantly poorer prognosis than the correctly assessed cases (P <
      0.05). Since multivariate logistic regression analysis showed that the
      significant risk factor related to the inaccurate intraoperative assessment of T
      stage was tumor size, the error in diagnosis may correlate with a greater degree
      of tumor spread. Surgeons should decide their therapeutic approach at the time of
      surgery on the basis of their intraoperative assessment of tumor spread. We
      recommend extensive surgery followed by adequate chemotherapy when serosal
      invasion is suspected at surgery.

PMID- 8159008
TI  - How does negative clinical evaluation of ovarian carcinoma after full course of
      chemotherapy correlate with second-look laparotomy findings?
AB  - Surgical reexploration was performed in 46 patients with epithelial nonmucinous
      ovarian adenocarcinoma requiring adjuvant chemotherapy whose initial therapy
      consisted of optimum debulking and surgical staging. All patients were placed on
      CAP (cisplatinum, Adriamycin, cyclophosphamide) chemotherapy for at least six
      courses until proved to be clinically disease free (mainly CA-125 below 35 U/ml
      and normal ultrasonography or computerized tomography). All women underwent
      second-look laparotomy (SLL) after completion of adjuvant therapy. We classified
      SLL findings in five categories, namely, no evidence of disease, cytological
      evidence of disease, histological evidence of disease, macroscopic evidence of
      disease (< 2 cm), and bulky tumor (> 2 cm). SLL demonstrated 14 (30%) patients
      with disease. Of these, five cases had histological evidence of disease and nine
      had macroscopic disease; however, we found no patient with persistent disease
      larger than 1.5 cm. No patient in stage I demonstrated disease at SLL. All cases
      with macroscopic disease and three cases with histological disease were initially
      in stage III. We found that about one third of cases who were clinically free of
      disease had persistent disease at the completion of chemotherapy. Hence, we
      conclude that routine SLL is still of importance in the management of patients
      with epithelial ovarian adenocarcinoma except those with stage I disease.

PMID- 8159009
TI  - A technique for lower one-third ureterectomy with bladder cuff excision.

PMID- 8159010
TI  - Eccrine porocarcinoma.
AB  - Eccrine porocarcinoma, a malignancy of the eccrine sweat glands, is extremely
      rare. Our report and a review of the literature (70 cases) emphasize the features
      of this tumor. Age at time of treatment ranged from 19 to 94 years (mean 67
      years). Duration of the lesion ranged from two months to 50 years; 31 (44%) had
      the lesion present > or = 5 years. Forty-four patients (62%) had tumors located
      on the extremities, 13 (19%) on the head and neck region and 12 (17%) on the
      trunk. All patients whose race is known were white. Primary treatment should
      consist of wide local excision and regional lymphadenectomy, if clinically
      indicated. Although there is a significant risk of cutaneous, regional lymph
      node, or visceral metastases, the value of elective or therapeutic regional
      lymphadenectomy is unknown, as is the role of adjunctive therapy.

PMID- 8159011
TI  - A mapped clock oscillator model for transmembrane electrical rhythmic activity in
      excitable cells.
AB  - Excitable cells such as smooth muscle, nerve, cardiac, and pancreatic beta cells
      exhibit rhythmic transmembrane depolarizations which have been modelled by
      nonlinear oscillators. This study deals with a general nonlinear oscillator with
      three different input portals. The oscillator consists of two coupled components:
      a clock which generates two interacting variables, and a transformer which maps
      the clock variables onto an observable output variable representing the
      transmembrane depolarizations. The clock determines the frequency, and the
      transformer determines the waveshape of the output. A computer model of the
      electrical rhythmic activity in gastric tissue was used as an example to
      illustrate the properties of the proposed oscillator model. A functional gastric
      oscillator may consist of a group of smooth muscles, or a group of interstitial
      cells of Cajal coupled to smooth muscles. Long, short and periodic pulses were
      applied to each input portal to examine their effects on the oscillator output
      with regards to amplitude and frequency characteristics, refractory properties,
      and entrainment properties, respectively.

PMID- 8159012
TI  - Is heterozygous advantage necessary for polymorphism in one-locus two-allele
      systems?
AB  - This paper presents a model of density-dependent selection in a continuously
      reproducing diploid population with two alleles at one locus. Using differential
      equations, we assume that the fertility of a mating pair is determined
      exclusively by the female. Genotypic fitness is defined as the average
      contribution of an individual of the genotype to the total population growth
      rate. The conditions for protected polymorphism are derived, and the most
      interesting new result is that genetic polymorphism does not necessarily require
      heterozygote superiority in fitness in diallelic one-locus systems if both
      fertility and viability selection are simultaneously operating in the population.

PMID- 8159013
TI  - Koinophilia stabilizes bi-gender sexual reproduction against asex in an
      unchanging environment.
AB  - Koinophilia, the tendency to choose mates with predominantly common phenotypic
      features, may be favourable because maladapted traits tend to have low
      frequencies. We used computer simulations to study competition between asexual
      and sexual reproduction, with and without koinophilia. The mutation process
      created new alleles, most of which were deleterious, but some small fraction was
      beneficial. With random mating, genderless sex (which does not suffer the two
      fold cost of producing males) had a modest advantage over asex, while bi-gender
      sex was rapidly replaced by asex. In contrast, koinophilia allowed sex to
      persist, even when males represented half the population. The advantage of
      koinophilia was greatest when populations were large, the incidence of mildly
      disadvantageous mutations was high, and beneficial mutations were rare. Under
      these circumstances koinophilic bi-gender sexual reproduction resisted
      replacement by asexuals for over 10,000 generations, even when one sexual mutated
      into a parthenogen every generation. Thus, koinophilia may be an important factor
      maintaining sexual reproduction.

PMID- 8159014
TI  - The intrinsic geometry of the cerebral cortex.
AB  - The mammalian cerebral cortex is a profoundly convoluted six-layered surface. The
      expansion of the cortex during evolution appears to be due to an increase in the
      number of functional units as opposed to an increase in the complexity of the
      units. Geometric similarity predicts that cortical area should increase in
      proportion to the 2/3 power of cortical volume. Allometric analysis has shown
      that in fact cortical area increases as a nearly linear function of cortical
      volume. This can be understood by appreciating that smaller brains tend to be
      smooth (lissencephalic) and larger brains fissured (gyrencephalic). This process
      of fissuration has reached its modern terrestrial limit in the human brain where
      the majority of the cortical surface is hidden within folds. The thickness of the
      cortex (2-3 mm) is small compared to its area (2000-2500 cm2) so the application
      of the techniques of differential geometry (the mathematics of idealized
      surfaces) is justified. Geometric properties of surfaces fall into two
      categories: intrinsic properties (which are invariant under folding of the
      surface, e.g. distances measured on the surface) and extrinsic properties (pure
      folding). The extrinsic geometry of the cortex determines the anatomical
      appearance of the cortex and the shape of the white matter. The intrinsic
      curvature of the cortex affects the relative position of functional areas and the
      spread of activity within the surface itself. A cortical surface has been
      reconstructed from cross-sections. Analysis of this surface has shown that the
      cortex has significant intrinsic curvature and hence it is wrong to regard it as
      merely a crumpled bag. The particular geometry observed is such that the surface
      is peculiarly "close together". Theoretical considerations and simulations
      suggest that the intrinsic geometry may have a significant effect on: the
      necessity of non-uniform growth in models of cortical development; the location
      of integrative areas; and the synchronization of neuronal firing. It is suggested
      that intrinsic descriptions of the cortex may prove more natural than extrinsic
      ones.

PMID- 8159015
TI  - Bifurcation, chaos and suppression of chaos in FitzHugh-Nagumo nerve conduction
      model equation.
AB  - We study the effect of constant and periodic membrane currents in neuronal axons
      described by the FitzHugh-Nagumo equation in its wave form. Linear stability
      analysis is carried out in the absence of periodic membrane current. Occurrence
      of chaotic motion, (i) in the absence of both constant and periodic membrane
      currents, (ii) with constant current only, (iii) with periodic membrane current
      only, and (iv) with both constant and periodic currents is investigated for
      specific parametric choices. We show how chaos sets in through a cascade of
      period doubling bifurcations. We then demonstrate the possibility of control of
      chaos using various control mechanisms. Specifically, we show the control of
      chaos by (i) adaptive control mechanism, (ii) periodic parametric perturbation
      and (iii) stabilization of unstable periodic orbits.

PMID- 8159016
TI  - High-dimensional simulation of simple immunological models.
AB  - We propose a simple model for idiotypic-antiidiotypic immunological networks
      which represents a simplification of the model originally suggested by Stewart &
      Varela, and de Boer, van der Laan & Hogeweg. Window cellular automata enlarge the
      antibody concentration if the influence of the immediate neighborhood lies
      between 70 and 99% of its maximum value; in addition random recruitment is
      possible. We simulate the model on large square lattices as well as in higher
      dimensions. The results are in qualitative agreement with those of the earlier
      model. Moreover, in five to ten dimensions we find phase separation for not too
      large recruitment, which then leads to domains growing to "infinity" for infinite
      times.

PMID- 8159017
TI  - Intermittent chaos in population dynamics.
AB  - In modelling single species with discrete, non-overlapping generations, one
      usually assumes that the density at time t + .1 is a function of the density at
      time t: Nt+1 = f(Nt). The dynamical behaviour of this system depends on the
      parameters in the function f. It commonly changes, as a parameter increases, from
      a stable equilibrium through a series of bifurcations into stable cycles, to
      chaotic motion. It is implicit in the assumptions of the model that the
      population consists of identical individuals. In this paper it is shown that
      variation within the population can lead to a different route to chaos. Invasion
      of a mutant phenotype into a resident population can elicit intermittency. This
      kind of chaotic behaviour consists of regular motion most of the time with short
      intermittent periods in which the system fluctuates wildly.

PMID- 8159018
TI  - Codon usage and evolutionary rates of proteins.
AB  - The 61 codons and the three terminators were counted in the coding sequences of
      31 families of proteins of higher vertebrates. The protein families were ordered
      according to their evolutionary rate. In each family, the ratio between the
      Observed and Expected frequency of each codon was obtained (O/E ratio). A strong
      and significant positive correlation was observed between the O/E ratio of the
      eight codons AAC, TAT, ATA, GAA, ACA, AAT, ATG and CGA and the evolutionary rate
      of the protein. A negative and significant correlation was observed for codons
      AAG and GAG. It was advanced that the functional constraints of proteins can
      influence the usage of codons, particularly for those trimers which are
      components of signal sequences. It was also observed that the O/E ratios of the
      terminators are negatively correlated with the evolutionary rate of the protein
      they terminate, and the correlation is significant for TAA and TGA, which in
      vertebrates might be older than TAG.

PMID- 8159019
TI  - Luria-Delbruck fluctuation experiments; accounting simultaneously for plating
      efficiency and differential growth rate.
AB  - Cells growing in culture are subject to mutation, and as mutation is a random
      event, the number of mutants in a culture will be a random variable. The size of
      the clone of mutants arising from a single mutational event depends on the timing
      of the mutation; the earlier the mutation the larger the corresponding clone of
      mutants. The frequency with which new mutations arise may be estimated from
      examining the number of mutants found in a number of parallel cultures, each
      culture arising from a single cell. An efficient estimator of mutation rate in
      such an experiment is a maximum likelihood estimator. The use of such an
      estimator presupposes knowledge of the probability distribution for the number of
      mutants to be detected in a culture, given the mutation rate. In turn this
      depends on the probability distribution for the size of the clone of detected
      mutants arising from any single mutation. This latter distribution depends on the
      relative cell cycle time, tau, of the mutants, and on the probability, s, that a
      mutant which exists will be detected. This paper develops the required
      probability distribution.

PMID- 8159020
TI  - Combination of cyclosporine and splenectomy suppresses interleukin-6 production
      and major histocompatibility complex class II expression and prolongs cardiac
      xenograft survival.
AB  - Although untreated Lewis rat recipients will reject a transplanted hamster heart
      in 3 days, accommodation of heart xenografts can be induced by treatment with
      cyclosporine and splenectomy, improving graft survival to greater than 50 days.
      Both humoral and cellular arms of the immune system may be involved in the
      mechanisms responsible for the prolongation of graft survival. Our objective was
      to study the impact of cyclosporine and splenectomy on the deposition of
      antibodies, complement, or both within the graft. We also compared the cellular
      component of inflammation in treated recipients with that in untreated controls.
      Inbred male Lewis rats given cyclosporine 15 mg/kg per day were splenectomized 2
      days after they had received heterotopic heart transplants from Golden Syrian
      hamsters. Recipients of syngeneic grafts or untreated xenografts served as
      controls. Plasma interleukin-6 activity was measured in a standard proliferation
      assay with 7TD1 hybridoma cells. Deposition of immunoglobulin M, immunoglobulin
      G, and complement in heart tissue was evaluated by immunofluorescence. Cells
      infiltrating the graft that expressed major histocompatibility complex class II
      antigens were identified by immunohistochemical staining with OX6 antibodies. In
      xenograft recipients receiving immunosuppression, interleukin-6 activity,
      immunoglobulin M and complement deposition were significantly reduced, graft
      infiltration was mild, and cardiac function was good compared with the results in
      those without treatment 3 and 10 days after implantation. Inflammatory cells
      expressing major histocompatibility complex class II antigens were significantly
      reduced in immunosuppressed xenograft recipients (2.8 +/- 0.4 cells/high power
      field) compared with those in xenogeneic controls (9.5 +/- 0.6 cells/high power
      field; p < 0.0005). The significant decrease in deposition of humoral components
      (immunoglobulin M and complement), interleukin-6 plasma levels, and expression of
      major histocompatibility complex class II antigens by inflammatory cells within
      the nonrejecting grafts suggests that the synergistic benefit of cyclosporine and
      splenectomy depends on the attenuation of both cellular and humoral mechanisms of
      xenograft rejection.

PMID- 8159021
TI  - Evaluation of cerebral metabolism and quantitative electroencephalography after
      hypothermic circulatory arrest and low-flow cardiopulmonary bypass at different
      temperatures.
AB  - Although widely used for repair of complex cardiovascular pathologic conditions,
      long intervals of hypothermic circulatory arrest and low flow cardiopulmonary
      bypass may both result in cerebral injury. This study examines cerebral
      hemodynamics, metabolism, and electrical activity to evaluate the risks of
      cerebral injury after 60 minutes of hypothermic circulatory arrest at 8 degrees
      C, 13 degrees C, and 18 degrees C, compared with 60 minutes of low flow
      cardiopulmonary bypass at 18 degrees C. Thirty-two puppies were randomly assigned
      to one of four experimental groups and centrally cooled to the appropriate
      temperature. Serial evaluations of quantitative electroencephalography,
      radioactive microsphere determinations of cerebral blood flow, calculations of
      cerebral oxygen consumption, cerebral glucose consumption, cerebral vascular
      resistance, cerebral oxygen extraction, systemic oxygen metabolism, and systemic
      vascular resistance were done. Measurements were obtained at baseline (37 degrees
      C), at the end of cooling, at 30 degrees C during rewarming, and at 2, 4, and 8
      hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. At
      the end of cooling, cerebral vascular resistance remained at baseline levels in
      all groups, but systemic vascular resistance was increased in all groups.
      Cerebral oxygen consumption became progressively lower as temperature was
      reduced: it was only 5% of baseline at 8 degrees C; 20% at 13 degrees C; and 34%
      and 39% at 18 degrees C. Quantitative electroencephalography was silent in the 8
      degrees C and 13 degrees C groups, but significant slow wave activity was present
      at 18 degrees C. Systemic vascular resistance and cerebral oxygen consumption
      returned to baseline values in all groups by 2 hours after hypothermic
      circulatory arrest or low flow cardiopulmonary bypass, but cerebral vascular
      resistance remained elevated at 2 and 4 hours, not returning to baseline until 8
      hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass.
      All but two of the long-term survivors (27 of 32) appeared neurologically normal;
      after hypothermic circulatory arrest at 8 degrees and 18 degrees C two animals
      had an unsteady gait. Comparison of quantitative electroencephalography before
      operation and 6 days after operation showed a significant increase in slow wave
      activity (delta activity) after hypothermic circulatory arrest and low flow
      cardiopulmonary bypass at 18 degrees C, a change that suggests possible cerebral
      injury. Although undetected after operation by simple behavioral and neurologic
      assessment, significant differences in cerebral metabolism, vasomotor responses,
      and quantitative electroencephalography do exist during and after hypothermic
      circulatory arrest and low flow cardiopulmonary bypass at various temperatures
      and may be implicated in the occurrence of cerebral injury.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8159022
TI  - A prospective, randomized comparison of cerebral venous oxygen saturation during
      normothermic and hypothermic cardiopulmonary bypass.
AB  - Recent reports have described cerebral venous oxygen desaturation during and
      after rewarming from hypothermic cardiopulmonary bypass. Additionally, patients
      undergoing normothermic cardiopulmonary bypass may be at higher risk for
      neurologic injury. This study was designed to determine whether patients
      undergoing normothermic cardiopulmonary bypass are at increased risk for
      sustained cerebral desaturation. Fifty-two patients undergoing first-time
      coronary artery bypass grafting were randomized to receive normothermic (37
      degrees C, n = 26) or hypothermic (27 degrees C, n = 26) cardiopulmonary bypass.
      The anesthetic was standardized and alpha-stat pH management was used. A 4F
      oximetric catheter was placed in the jugular bulb and cerebral venous and radial
      arterial blood were sampled. Oxygen partial pressure and saturation were measured
      at six intervals from cerebral venous blood and from radial arterial blood.
      Patients receiving normothermic cardiopulmonary bypass had lesser values of
      oxygen partial pressure and saturation in cerebral venous blood than patients
      subjected to hypothermia during the first 40 minutes of bypass. Cerebral venous
      desaturation (oxygen saturation in cerebral venous blood of 50% or less) was
      observed in 54% of patients in the normothermic group and 12% of patients in the
      hypothermic group during cardiopulmonary bypass. In the normothermic group,
      cerebral desaturation occurred primarily in early bypass (14 of 26). The three
      episodes of desaturation in the hypothermic group occurred during rewarming.
      During cardiopulmonary bypass, the arteriovenous oxygen content difference was
      greater in the normothermic group than in that in the hypothermic group,
      suggesting higher oxygen consumption. Differences in glucose utilization during
      early cardiopulmonary bypass between the groups was also detected. One patient in
      the hypothermic group had an embolic stroke and subsequently died. There were no
      other perioperative strokes or deaths in the study population. The present study
      demonstrates that patients undergoing normothermic cardiopulmonary bypass are at
      greater risk for cerebral desaturation. Because it is a global assessment,
      cerebral venous oxygen saturation may be insensitive to focal ischemic events. It
      remains to be seen whether these differences in cerebral physiologic states
      translate into differences in clinical outcome.

PMID- 8159023
TI  - Arterial line filtration protects brain microcirculation during cardiopulmonary
      bypass in the pig.
AB  - Microemboli in the brain may inhibit brain function during cardiopulmonary
      bypass, and in a previous study in pigs of normothermic nonpulsatile bypass we
      reported a significant decrease in cerebral glucose consumption secondary to
      interruption of the capillary flow, possibly caused by microemboli. In the
      present study we measured the regional cerebral glucose consumption and the
      regional capillary diffusion capacity (that is, the number of perfused
      capillaries) in 10 different brain regions in two separate groups of animals with
      and without an arterial filter during normothermic cardiopulmonary bypass.
      Inclusion of a 40 micron arterial filter in the bypass circuit increased the
      regional brain glucose consumption 27% (median; range -12% to 145%) and regional
      capillary diffusion capacity increased 123% (median; range 36% to 829%). No
      change in brain histologic features, the cerebrovascular permeability to serum
      proteins, or cerebral water content was observed. The arterial filter probably
      protects the cerebral microcirculation and prevents the decrease in cerebral
      glucose consumption otherwise seen during bypass.

PMID- 8159024
TI  - Regional cerebral perfusion abnormalities after cardiac operations. Single photon
      emission computed tomography (SPECT) findings in children with postoperative
      movement disorders.
AB  - Despite the clinical and pathologic indicators implicating injury to the basal
      ganglia in children with hyperkinetic movement disorders, we were previously
      unable to identify lesions in these structures by means of cranial computed
      tomography or magnetic resonance imaging. We evaluated regional cerebral
      perfusion measured by single photon emission computed tomography (SPECT) with
      technetium 99m hexamethyl propylene amine oxime as a technique to localize
      functional cerebral abnormalities in eleven children who had a movement disorder
      after hypothermic cardiac surgery. Perfusion defects of the deep gray matter were
      noted in six of these eleven patients and cortical perfusion defects in nine. For
      both cortical and subcortical defects a strong right-sided predilection was
      present. Our findings suggest functional brain injury not detectable by
      conventional cranial computed tomography and magnetic resonance imaging in these
      patients. We speculate that these perfusion defects might relate to the
      behavioral and developmental sequelae in survivors of this syndrome. SPECT may
      identify subclinical injury in patients at risk for future neurodevelopmental
      problems and contribute to our understanding of the mechanisms of cerebral injury
      in the patient operated on for cardiac disease.

PMID- 8159025
TI  - Hemodynamic and cerebral repercussions arising from surgical interruption of the
      superior vena cava. Experimental model.
AB  - This study was designed to analyze the hemodynamic and cerebral repercussions
      arising from the surgical interruption of the superior vena cava. The experiments
      were carried out in 12 mongrel dogs under two different conditions: with shunt
      (group A, n = 6) and without the installation of a shunt (group B, n = 6). The
      period of occlusion was 35 minutes. The right atrium pressure, pulmonary arterial
      pressure, and aortic pressure are not significantly modified in the two groups.
      The intracranial pressure had an important correlation with the central venous
      pressure (r2 = 0.8572). In group B, the intracranial pressure had a sharp
      increase between the basal period (6.9 +/- 1.47 mm Hg) and the clamping superior
      vena cava (17.2 +/- 1.05 mm Hg), accentuated with the interruption of the azygous
      vein (32.2 +/- 0.7 mm Hg). In group A, the use of a shunt avoided this alteration
      during clamping of the superior vena cava (6.8 +/- 2.0 mm Hg) and the azygous
      vein (8.0 +/- 2.24 mm Hg). However, after removal of the clamps in group B, an
      elevated residual intracranial pressure was observed (21.1 +/- 3.33 mm Hg) in
      contrast to the central venous pressure, which returned to the basal values (4.4
      +/- 0.7 mm Hg). The biomechanic findings of the volume-pressure curves (with
      Miller and Marmarou-Shapiro tests) and the cerebral necropsy showed brain damage
      in group B, without the shunt. Three animals had areas of hemorrhagic infarction.
      Histologic study demonstrated signs the incipient vasogenic edema. In group A,
      all findings were compatible with the normal. In conclusion, these results
      suggest the importance of shunting the blood in those cases of a nonobstructed
      superior vena cava because the clamping and reconstruction produce hemodynamic
      compromise and brain damage.

PMID- 8159026
TI  - Hypothermic potassium cardioplegia impairs myocyte recovery of contractility and
      inotropy.
AB  - Acute postoperative left ventricular dysfunction after hypothermic, crystalloid
      potassium cardioplegia occasionally occurs. This project examined myocyte
      contractility and inotropic responsiveness after hypothermic arrest with and
      without potassium cardioplegia. Isolated swine left ventricular myocytes were
      placed in a thermostatically controlled chamber (37 degrees C) that contained a
      standard cell medium, pulse stimulated at 1 Hz, and steady-state contractions
      were measured by computer-assisted video microscopy with and without
      isoproterenol (25 nmol/L). After baseline measurements were taken the myocytes
      were randomly assigned to the following treatments: (1) control group with
      infusion of 37 degrees C crystalloid solution and maintained at 37 degrees C for
      3 hours (n = 23), (2) hypothermia group with infusion of 4 degrees C crystalloid
      without potassium and stored at 4 degrees C for 3 hours (n = 22), (3) hypothermic
      cardioplegia group with infusion of a crystalloid cardioplegia (oxygenated,
      buffered 4 degrees C Ringer's solution with 24 mEq/L K+) and then stored at 4
      degrees C for 3 hours (n = 35). After treatment the myocytes were then rewarmed
      to 37 degrees C by infusion of medium, and contractile measurements were
      repeated. In the control group, the percent and velocity of shortening were
      identical to those in baseline measurements: 6.4% +/- 0.4% and 53 +/- 5
      microns/sec, respectively, and these values remained unchanged in the hypothermia
      group: 6.5% +/- 0.4% and 51 +/- 3 microns/sec, respectively. However, in the
      hypothermic cardioplegia group, the percent and velocity of shortening were
      significantly lower with rewarming: 4.8% +/- 0.4% and 35 +/- 3 microns/sec,
      respectively, p < 0.05). Isoproterenol caused increased percent and velocity of
      shortening in both the control and hypothermia groups: 10.0% +/- 0.6% and 9.5% +/
      0.9% and 81.6 +/- 8 microns/sec and 71.4 +/- 8 microns/sec, respectively. This
      response was significantly blunted in the cardioplegia group (8.9% +/- 0.8% and
      56.9 +/- 7 microns/sec, p < 0.05). With an isolated myocyte system that is
      independent of extracellular and perfusion effects, hyperkalemic cardioplegic
      solution resulted in depressed myocyte contractile performance after rewarming.
      Potassium cardioplegia also caused a blunted inotropic responsiveness on
      rewarming. A potential contributory factor for the depressed left ventricular
      function after the use of potassium cardioplegia is a direct depression in
      myocyte contractility.

PMID- 8159027
TI  - Surgical treatment of Barrett's carcinoma. Correlations between morphologic
      findings and prognosis.
AB  - Barrett's carcinoma occurred in 66 of 331 patients with adenocarcinomas of the
      esophagus or gastroesophageal junction. Only 32 (46%) of these patients had a
      history of gastroesophageal reflux. A history of alcohol and tobacco abuse was
      absent in 50% and 47.5%, respectively. The mean length of Barrett's metaplasia
      was 7.37 cm. Operability was 98.5% and resectability 95.5%. No postoperative or
      hospital deaths occurred. Pathologic staging was as follows: stage 0 and I,
      38.3%; stage II, 20.6%; stage III, 22.2%; and stage IV, 19%. Overall survivals
      were 80.5% at 1 year, 62.7% at 2 years, and 58.2% at 5 years. Five-year survival
      for patients with stage I disease was 100%; for stage II, 87.5%; for stage III,
      22.2%; and for stage IV, 0%. Thirty-four (51.5%) patients were under surveillance
      for a related or unrelated condition before diagnosis of their carcinoma; only
      nine (26.5%) had diseased lymph nodes. In 32 the diagnosis was made at their
      first medical contact, and 78% of them had diseased lymph nodes. Five-year
      survival without nodal metastasis was 85.3% and significantly better than for
      patients with metastasis, 38.3% (p = 0.0033). Of the 66 patients, 19 (28.7%) had
      a biopsy-proved history of Barrett's metaplasia before malignancy developed. Mean
      time interval between diagnosis of metaplasia and degeneration was 3.8 years
      (89.5% > 1 year). Over the surveillance period, the length of metaplastic
      Barrett's esophagus remained unchanged in all patients. Barrett's ulceration was
      present from the beginning in 14 patients, and three patients never had an ulcer.
      Intestinal metaplasia was seen in 18 patients. Resected specimens revealed severe
      dysplasia in 16 patients. Of the 19 patients, 73.7% had stage I disease. Our data
      suggest that close endoscopic monitoring and systematic biopsies of the smallest
      irregularities in the metaplastic mucosa may result in early detection of
      carcinoma. In this respect, patients with an ulcer within a zone of intestinal
      metaplasia seem to be at risk. Early detection increases substantially the
      chances for cure by diminishing the risks of lymph node involvement. Resection
      remains the treatment of choice in Barrett's adenocarcinoma including high-grade
      dysplasia, because mortality can be kept low with excellent to very good
      functional results in the majority of the patients provided the intervention is
      performed by experienced teams.

PMID- 8159028
TI  - Retrosternal ileocolic esophageal replacement in children revisited. Antireflux
      role of the ileocecal valve.
AB  - The risk of postoperative reflux and pulmonary aspiration with straight colon or
      gastric tube esophageal replacement in children prompted us to reevaluate the
      presumed antireflux role of the ileocecal valve with retrosternal ileocolic
      interposition. This operation was done in eight patients with esophageal atresia
      (six) and lye stricture (two) from 19 to 50 months of age between 1983 and 1992.
      There were no operative deaths. The duration of follow-up ranged from 4 to 115
      months. Barium swallow obtained in all patients showed unobstructed
      esophagoileocolic transit without reflux. Two patients with esophageal atresia
      had localized proximal anastomotic leaks, which healed spontaneously without
      stricture. In the two patients with lye ingestion ileoesophageal strictures
      developed that necessitated revision. None of the patients had postoperative
      respiratory complications or symptomatic gastroesophageal reflux. All eight
      children have had their gastrostomy tubes removed, are eating a regular diet, and
      are growing well. In conclusion, the retrosternal ileocolic conduit provides an
      excellent substitute esophagus in selected pediatric patients, with potential
      advantages over delayed primary anastomosis or the straight colon or gastric tube
      interposition because of the antireflux role of the ileocecal valve.

PMID- 8159029
TI  - How extensive should lymph node dissection be for cancer of the thoracic
      esophagus?
AB  - From 1985 to 1992, 171 patients with cancer of the thoracic esophagus underwent
      esophagectomy with systematic dissection of regional lymph nodes including
      cervical nodes. The hospital mortality rate was 5.3%. The dissected nodes were
      classified into four groups: the deep cervical (C), upper mediastinal and
      cervical paratracheal (U), middle and lower mediastinal (L), and upper
      perigastric (G) groups. The U group mainly consisted of nodes beside the
      recurrent laryngeal nerves. The phase of cancer infiltration of lymph nodes was
      evaluated by the total number and the distribution of involved nodes. Of cases
      with nodal involvement, only 37% were in the late phase, in which more than seven
      nodes or in which the U, L, and G groups were all involved. Of cases in the
      earliest phase in which only one node was involved, 93% had either the U or G
      group involved. The C group of nodes was infrequently involved until the late
      phase. Cancer had metastasized to the U and G groups across a considerable
      anatomic distance even in earlier phases. Outcomes of the cases with nodal
      involvement not in the late phase were satisfactory; the cumulative survival was
      60% at 3 years and 54% at 5 years. Systematic nodal dissection would benefit even
      cases with nodal involvement, unless the disease is in the late phase. Nodes
      beside the recurrent nerves and upper perigastric nodes should be dissected with
      higher priority, though they are located anatomically distant.

PMID- 8159030
TI  - Prevalence of chronic pain after pulmonary resection by thoracotomy or video
      assisted thoracic surgery.
AB  - The prevalence and severity of chronic pain after video-assisted thoracic surgery
      for pulmonary resection remains to be defined. Three hundred forty-three of 391
      consecutive patients 3 to 31 months after pulmonary resection by lateral
      thoracotomy (n = 165) or video-assisted thoracic surgery (n = 178) responded to a
      questionnaire aimed at comparing the relative occurrence of chronic postoperative
      pain after video-assisted thoracic surgery and lateral thoracotomy approaches for
      pulmonary resection. Patients less than 1 year after operation (video-assisted
      thoracic surgery = 142; thoracotomy = 97) and more than 1 year after operation
      (video-assisted thoracic surgery = 36; thoracotomy = 68) were analyzed as
      individual cohorts. Chronic pain was assessed by questioning patients about the
      presence and the intensity of discomfort on the side of the operation (using a
      visual analog scale) and their need for analgesic medication and the presence of
      ongoing limitations in shoulder function. Patients who underwent video-assisted
      thoracic surgery (less than 1 year from operation) had less pain and subjective
      shoulder dysfunction although their pain medication requirements were similar to
      those of thoracotomy patients less than 1 year from operation. After 1 year,
      there was no significant difference in these "pain related" morbidity parameters
      between the two surgical approach groups (video-assisted thoracic surgery or
      thoracotomy).

PMID- 8159031
TI  - Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma. Five
      year survival and patterns of intrathoracic recurrence.
AB  - One hundred seventy-three patients with stage I (T1 N0, T2 N0) non-small-cell
      lung cancer underwent either a segmental pulmonary resection (n = 68) or
      lobectomy (n = 105) from 1980 to 1988. Four patients were lost to follow-up, but
      the remaining 169 patients were followed up for 5 years. Survival and the
      prevalence of local/regional recurrence were assessed. Although no survival
      advantage of lobectomy over segmental resection was noted for patients with
      tumors 3.0 cm in diameter or smaller, a survival advantage was apparent for
      patients undergoing lobectomy for tumors larger than 3.0 cm. The rate of
      local/regional recurrence was 22.7% (15/66) after segmental resection versus 4.9%
      (5/103) after lobectomy. A review of histologic tumor type, original tumor
      diameter, and segment resected revealed no risk factors that were predictive of
      recurrence. An additional resection for recurrence was performed in four
      patients. Lobectomy is the preferred operative procedure for patients with stage
      I tumors larger than 3.0 cm. Because the rate of local/regional recurrence was
      high after segmental resections, diligent follow-up of these patients is
      mandatory.

PMID- 8159032
TI  - Carcinogen-specific mutations in the p53 tumor suppressor gene in lung cancer.
AB  - Mutations of the p53 tumor suppressor gene, whose encoded protein is one of the
      chief regulators of the cell cycle, are proving to be the most common genetic
      alteration in human cancer. Point mutations have been detected in numerous human
      solid tumors. The types of point mutations in the p53 gene vary considerably in
      different kinds of human cancers, suggesting that specific etiologic agents are
      responsible for typical kinds and sites of mutations in the p53 gene. This study
      reports the detection of two unusual p53 mutations in a series of patients with
      lung cancer. The first case showed a one-base pair deletion at the end of exon 8,
      which is rarely affected by mutations, leading to a frameshift involving the
      following intron 8, exon 9, and intron 9. The second case exhibited two point
      mutations in codon 273, both either localized in the same codon on one allele or
      each mutation localized on a different allele in codon 273. Interestingly, the
      two mutations can be attributed to different mechanisms of base substitution.
      This is the first report of this kind. Because of evidence that the nature and
      site of p53 mutations reflect not only the mutagens involved in tumorigenesis but
      also the capacity for malignant transformation, the characterization of mutations
      of the p53 gene may provide a basis for assessing further risk factors, as well
      as for estimating prognosis in patients with lung cancer.

PMID- 8159033
TI  - Outcomes in patients with interrupted aortic arch and ventricular septal defect.
      A multiinstitutional study. Congenital Heart Surgeons Society.
AB  - Among 183 neonates with interrupted aortic arch and ventricular septal defect
      entering a multiinstitutional study between 1987 and 1992, nine died before
      repair was accomplished. Among the remaining 174, survival at 1 month and 1, 3,
      and 4 years after repair was 73%, 65%, 63%, and 63%, respectively. The risk
      factors for death were low birth weight, younger age at repair, interrupted arch
      type B, outlet and trabecular ventricular septal defects, smaller size of the
      ventricular septal defect, and subaortic narrowing. Echocardiographically
      measured dimensions (expressed as Z-values) at all levels of the left heart-aorta
      complex were small. Two among thirty institutions were risk factors, and two
      others possibly were. Procedural risk factors for death after repair were (1)
      repair without concomitant procedures in patients with other important levels of
      obstruction in the left heart-aorta complex, (2) a Damus-Kaye-Stansel
      anastomosis, and (3) subaortic myotomy/myectomy in the face of subaortic
      narrowing. One-stage repair plus ascending aorta/arch augmentation had the
      highest predicted time-related survival in the 20% of patients with interrupted
      aortic arch and one or more coexisting levels of obstruction in the left heart
      aorta complex, as did initial repair without or with aorta/arch augmentation in
      the 80% without these.

PMID- 8159034
TI  - Extended aortic valvuloplasty for recurrent valvular stenosis and regurgitation
      in children.
AB  - Recurrent significant aortic valvular stenosis or regurgitation, or both, after
      balloon or open valvotomy in pediatric patients often necessitates aortic valve
      replacement. In an attempt to preserve the aortic valve, we performed extended
      aortic valvuloplasty in 21 children with recurrent aortic valve stenosis or
      regurgitation from January 1989 to March 1993. Previous related procedures were
      one open aortic valvotomy or more (n = 15), balloon valvotomy (n = 4), balloon
      valvotomy after surgical valvotomy (n = 1), and repair of iatrogenic valve tear
      (n = 1). Mean age at the time of the extended aortic valvuloplasty was 6 +/- 3.4
      years. Mean pressure gradient across the aortic valve was 56 +/- 12 torr.
      Regurgitation was moderate (grade 2 to 3) in nine and severe (grade 4) in 12
      patients. Extended aortic valvuloplasty techniques consisted of thinning of valve
      leaflets (n = 15), augmentation of scarred and retracted leaflets with autologous
      pericardium (n = 11), resuspension of the augmented leaflet (n = 14), release of
      the rudimentary commissure from the aortic wall (n = 5), extension of the
      valvotomy incision into the aortic wall on both sides of the commissure (n = 20),
      patch repair of the sinus of Valsalva perforation (n = 1), reapproximation of
      tears (n = 5), and narrowing of the ventriculoaortic junction (n = 2). No
      operative deaths occurred. The postoperative mean pressure gradient, assessed by
      most recent Doppler echocardiography or cardiac catheterization at a follow-up of
      18 +/- 6 months, was 19 +/- 6 torr (p < 0.01 versus the preoperative gradient).
      Aortic regurgitation was absent in 13, mild in 6, and moderate-to-severe,
      necessitating subsequent aortic valve replacement, in 2. This short-term
      experience indicates that extended aortic valvuloplasty is a safe and effective
      surgical approach that minimizes the need for aortic valve replacement in
      children with significant recurrent aortic valve stenosis or regurgitation.

PMID- 8159035
TI  - Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for
      congenital heart defects.
AB  - Seventeen infants were treated with inhaled nitric oxide for critical pulmonary
      artery hypertension after operations for congenital heart defects. In all 17
      patients conventional medical therapy consisting of hyperventilation, deep
      sedation/analgesia, and correction of metabolic acidosis had failed. All children
      were monitored with a transthoracic pulmonary artery catheter inserted at
      operation. Pulmonary artery hypertension was defined as an acute rise in
      pulmonary pressure associated with a decrease in oxygen arterial or venous
      saturation. After failure of conventional medical therapy, 20 ppm of inhaled
      nitric oxide was administered to the patient. In all patients the pulmonary
      pressures decreased (mean pulmonary arterial pressure decreased by -34% +/- 21%)
      without significant change in systemic arterial pressure, whereas the oxygen
      arterial saturation and oxygen venous saturation increased by 9.7% +/- 12% and
      37% +/- 28%, respectively. Fifteen children were discharged from the intensive
      care unit at 10 +/- 6 days (range 3 to 26 days) and two died. This study
      demonstrates that inhaled nitric oxide exerts a selective pulmonary vasodilation
      without decreasing systemic arterial pressure in children with congenital heart
      disease. The increased values of mixed venous oxygen saturation and urinary
      output suggest that this selective lowering of pulmonary vascular resistance
      improved the overall hemodynamics. The potential toxic effects of nitric oxide
      and nitrogen dioxide necessitate careful consideration of the risks and benefits
      of inhaled nitric oxide therapy.

PMID- 8159036
TI  - Lower intensity anticoagulation therapy results in lower complication rates with
      the St. Jude Medical prosthesis.
AB  - Six hundred consecutive patients were operated on between September 1978 and
      October 1982 for isolated aortic (n = 298), mitral (n = 215), or multiple valve
      replacement (n = 87) with the St. Jude Medical bileaflet prosthesis. Mean age of
      the 303 female and 297 male patients was 50.7 +/- 9.6 (range 12 to 83) years. All
      patients were followed up prospectively; follow-up was complete and averaged
      122.2 +/- 1.1 months for operative survivors. Total follow-up for aortic patients
      was 2904.1 patient-years, for mitral replacement 1859.5 patient-years, and for
      multiple valve replacement 736 patient-years. When the prothrombin times measured
      with different thromboplastins were converted into an international normalized
      ratio, four patient groups could be separated; that is, the groups comprised
      patients whose anticoagulation was maintained during the follow-up within an
      international normalized ratio corridor of 4.0 to 6.0, 3.0 to 4.5, 2.5 to 3.5, or
      1.75 to 2.75. Less intensive anticoagulation in terms of the international
      normalized ratio values caused only a mild increase in the incidence of
      thromboembolic complications but a highly significant decrease in the rate of
      bleeding. Severe bleeding complications in the aortic valve group were highest
      with an international normalized ratio of 4.0 to 6.0 (1.15 per patient-year) and
      lowest with an international normalized ratio of 1.75 to 2.75 (0.24 per patient
      year). The same held true for patients with single St. Jude Medical mitral valve
      replacement (2.09 per patient-year versus 0.72 per patient-year) and multiple
      valve replacements (4.45 per patient-year versus 1.20 per patient-year). These
      results suggest that the generally recommended international normalized ratio of
      3.0 to 4.5 may be too high for patients with St. Jude Medical aortic valve
      replacement and also for patients with St. Jude Medical prostheses in the mitral
      position if, with respect to the thromboembolic hazard, there is not a
      predominating patient-related comorbidity. A large multicenter prospective
      randomized study is therefore proposed to establish the safe international
      normalized ratio levels accompanied by the lowest complication rates for both
      bleeding and thromboembolic events after St. Jude Medical prosthesis implantation
      (German experience with low intensity anticoagulation study).

PMID- 8159037
TI  - Effects of antiplatelet therapy with indobufen or aspirin-dipyridamole on graft
      patency one year after coronary artery bypass grafting.
AB  - Saphenous vein coronary artery bypass graft patency can be increased by
      antiplatelet therapy. Aspirin plus dipyridamole are effective but are associated
      with tolerability problems. Indobufen is a possible alternative antiplatelet
      agent that may be better tolerated. A prospective, randomized, double-blind,
      parallel-group study was undertaken to compare the efficacy and safety of
      indobufen 200 mg twice daily with aspirin 300 mg thrice daily plus dipyridamole
      75 mg thrice daily in preventing occlusion of autologous saphenous vein coronary
      artery bypass grafts. A total of 803 patients were randomized in the study, of
      whom 552 had a follow-up coronary angiogram approximately 1 year after operation.
      All anastomoses were patent in 56% of indobufen-treated patients and 59% of
      aspirin-dipyridamole recipients (p = 0.384). The percentage of all anastomoses
      patent was 82% in the indobufen group and 83% in the aspirin-dipyridamole group
      (p = 0.297). Mean postoperative blood loss was significantly less in the
      indobufen group (p = 0.043). Patients who received indobufen also had
      significantly fewer adverse events considered to be treatment-related compared
      with aspirin-dipyridamole recipients (p = 0.02). At the doses tested indobufen
      was as effective as aspirin plus dipyridamole in preventing occlusion of
      saphenous vein grafts and was better tolerated. Because indobufen was associated
      with less postoperative blood loss it may be used before operation in coronary
      artery bypass grafting.

PMID- 8159038
TI  - Invited letter concerning: how extensive should lymph node dissection be for
      cancer of the thoracic esophagus?

PMID- 8159039
TI  - The in vitro response of human internal mammary artery to vasodilators.

PMID- 8159040
TI  - The sternal saw: a historical note with a modern message.

PMID- 8159041
TI  - Patent ductus arteriosus open for clipping?

PMID- 8159042
TI  - Neutrophil elastase release and cardiopulmonary bypass.

PMID- 8159043
TI  - Accelerated degeneration of aortic homograft in an infant.

PMID- 8159044
TI  - Invited letter concerning: accelerated degeneration of aortic allografts in
      infants and young children.

PMID- 8159045
TI  - Myocardial ischemia caused by postoperative internal thoracic artery steal.

PMID- 8159046
TI  - Fortuitous detection of prosthetic valve endocarditis caused by an uncommon
      etiologic agent.

PMID- 8159047
TI  - Modification of Heron's technique for heterotopic cardiac transplantation in
      rats.

PMID- 8159048
TI  - A symptomatic thymic cyst in the middle mediastinum.

PMID- 8159049
TI  - Univent endotracheal tube: twelve-year experience.

PMID- 8159050
TI  - An unusual case of anomalous origin of the left coronary artery and mitral valve
      regurgitation in an eight-year-old boy.

PMID- 8159051
TI  - Pediatric lung transplantation. Indications, techniques, and early results.
AB  - From July 1990 to April 1993, 36 lung transplantations in 33 patients were
      performed in our pediatric transplant program (0.25 to 23 years, mean age 10.3
      years). Eight children had been continuously supported with a ventilator for 3
      days to 4.5 years before transplantation and three were supported by
      extracorporeal membrane oxygenation. Indications for lung transplantation in this
      pediatric population included the following: cystic fibrosis (n = 13), pulmonary
      hypertension, and associated congenital heart disease (n = 10), pulmonary
      atresia, ventricular septal defect and nonconfluent pulmonary arteries (n = 3),
      pulmonary fibrosis (n = 6), and acute respiratory distress syndrome (n = 1).
      Three children underwent retransplantation for acute graft failure (n = 2) or
      chronic rejection (n = 1). Pulmonary fibrosis was related to complications of
      treatment of acute of myelogenous leukemia with bone marrow transplantation in
      two children and to bronchiolitis obliterans, bronchopulmonary dysplasia,
      interstitial pneumonitis, and Langerhans cell histiocytosis in four others.
      Thirteen children underwent lung transplantation and concomitant cardiac repair.
      Bilateral lung transplantation, ventricular septal defect closure and pulmonary
      homograft reconstruction of the right ventricular outflow tract to the
      transplanted lungs was performed in three children by means of a new technique
      that avoids the need for combined heart-lung transplantation. Two patients had
      ventricular septal defect closure and single lung transplant for Eisenmenger's
      syndrome, two had ligation of a patent ductus arteriosus and transplantation,
      three additional children underwent atrial septal defect closure and lung
      transplantation, and two underwent lung transplantation for congenital pulmonary
      vein stenosis. Eight early deaths and three late deaths occurred (actuarial 1
      year survival 62%). Lung transplantation in children has been associated with
      acceptable early results, although modification of the adult implantation
      technique has been necessary. Lung transplantation and repair of complex
      congenital heart defects is possible; heart-lung transplantation may only be
      required for patients with severe left heart dysfunction and associated pulmonary
      vascular disease. Bronchiolitis obliterans remains a major concern for long-term
      graft function in pediatric lung transplant recipients.

PMID- 8159052
TI  - [Blood lead in a population of children with iron deficiency].
AB  - BACKGROUND: Analysis of blood lead levels in relation to the state of iron
      metabolism was carried out in children. METHODS: A transversal study of blood
      lead levels was designed in 89 iron deficient children (serum ferritin < 15
      micrograms/l) (group F). Fifty seven of the children did not have anemia (sub
      group FS) and 32 had anemia (sub-group AF) with ages ranging between 6 months and
      14 years, and 41 children of the same age with normal iron metabolism (group C).
      A longitudinal study was also carried out by the determination of blood lead
      levels prior and after iron therapy in 18 of the iron deficient children.
      RESULTS: A significant difference was seen between the mean of blood lead levels
      in iron deficient children (group F), 9.41 micrograms/dl and normal children
      (group C), 6.88 micrograms/dl (p < 0.01). The mean of blood lead levels of the
      sub-group FS was 7.79 micrograms/dl and the sub-group AF, 12.30 micrograms/dl (p
      < 0.01). The prevalence of lead poisoning (blood lead levels > 20 micrograms/dl)
      was 8% in group F (2% in sub-group FS, 19% in sub-group AF) and 0 in group C (p <
      0.01). A significant decrease was found in the longitudinal study in the mean of
      blood lead levels following iron therapy from 14.12 micrograms/dl to 7.51
      micrograms/dl (p < 0.05). CONCLUSIONS: The iron deficient state may constitute a
      predisposing factor of lead poisoning in childhood.

PMID- 8159054
TI  - [Infection by the human immunodeficiency virus type 1 in the population of
      prisoners of Catalonia].
AB  - BACKGROUND: The prison population represents a high risk group for the human
      immunodeficiency virus type 1 infection. The present study was carried out to
      know the prevalence of infection in this collective in three penitentiary centers
      in Catalonia. METHODS: All the subjects who were in or who were admitted to the
      three penitentiaries for men from October 1987 to April 1988 were included in the
      study (n = 1,579). Demographic risk factor and penitentiary variables were
      obtained. The determination of anti-HIV-1 antibodies was performed by
      enzymoimmunoanalysis (Dupont HIV ELISA). RESULTS: The global prevalence of HIV-1
      infection was of 40.6%. Significant statistical differences were found among
      intravenous drug users (IVDU) and non IVDU (chi 2 = 376.8, p < 0.0001, OR = 9.6,
      CI 95% = 7.5 - 12.3) and between habitual and sporadic users (chi 2 = 23.9, p <
      0.0001, OR = 3.0, CI 95% = 1.9 x 4.7). CONCLUSIONS: The penitentiary population
      in Catalonia is a collective with a high prevalence of infection by the human
      immunodeficiency virus type 1, with intravenous drug use being the fundamental
      factor associated to this prevalence.

PMID- 8159053
TI  - [Incidence of enteropathogens in patients with human immunodeficiency virus
      infection].
AB  - BACKGROUND: To establish the incidence of diarrhea and its evolution over time,
      the causal microorganisms, recurrence and associated mortality in patients with
      AIDS or severe immunologic alterations (CD4 lymphocytes lower than 0.5 x
      10(9)/l). METHODS: A prospective longitudinal study was carried out from 1984 to
      1992. The following patients were included in the study: 1) all those patients
      with diarrhea in whom a pathogenic microorganism was identified in the stools,
      and 2) patients with fever and positive blood cultures for enteropathogenic
      bacteria. The patients belonged to a series of 1,456 patients with infection by
      HIV. RESULTS: Of the 1,456 controlled patients, 253 (17%) had infection by
      enteropathogenic microorganisms. The incidence was greater in homosexual patients
      (26%) than in drug addicts (12%). The most frequent germs were Cryptosporidium,
      in 104 episodes and Salmonella sp. in 78 episodes (31 as isolated bacteria). The
      mortality in the 15 days following isolation was 2%, the referred microorganisms
      being the most frequent responsible for the deaths. The mean of CD4 lymphocytes
      in the patients with enteropathogens was 0.17 x 10(9)/l). SD 0.14 x 10(9)/l). In
      patients with infection by Cryptosporidium the CD4 lymphocyte count was lower
      than that observed in the cases of infection by Isospora belli. Prior to 1988,
      21% of the patients had infection by enteropathogenic bacteria and 23% by
      parasites, those percentages being 3% and 6%, respectively in 1991. CONCLUSIONS:
      Infections by enteropathogenic microorganisms in patients with infection by the
      human immunodeficiency virus in an advanced stage are frequent, particularly, in
      homosexuals. The patients with enteritis by Cryptosporidium have a greater grade
      of immunosuppression (CD4 lymphocytes lower than 0.1 x 10(9)/l) than patients
      with infection by other enteropathogenic microorganisms. In the last few years,
      the incidence of enteropathogenic bacteria, especially Salmonella sp. and
      protozoa has decreased [corrected].

PMID- 8159055
TI  - [Assessment of renal function in progressive nephropathy. A challenge for
      contemporary medicine and a dilemma for the Third World].

PMID- 8159056
TI  - [The elderly abuse syndrome].

PMID- 8159057
TI  - [Isolated ACTH deficiency].
AB  - The isolated ACTH deficiency is a scarcely diagnosed disease of heterogeneous
      nature. Two patients with isolated deficiency of ACTH in whom the initial
      diagnosis was of primary suprarrenal failure are reported. In the first case this
      diagnosis was performed after hospital admission for deterioration of the level
      of consciousness and the development of an acute suprarrenal crisis in the course
      of nosocomial pneumonia. In the second case the clinical manifestations began as
      weakness, anorexia, weight loss and lymphocytosis with eosinophilia. In both
      patients an increase in the thyrotropic hormone was detected leading to suspicion
      of the existence of associated primary hypothyroidism. Finally, several studies
      were carried out (basal measurements of cortisol and ACTH, stimulation with
      continual perfusion of ACTH, insulinic hypoglycemia, global study of
      adenohypophysary function, ACTH CRF release factor test, computerized tomography
      of the pituitary region) in both patients leading to the definitive diagnosis of
      isolated ACTH deficiency of idiopathic cause of possible pituitary origin without
      the existence of other associated hormonal deficiencies.

PMID- 8159058
TI  - [Clinical indications and risks of fresh frozen plasma. General Subdirectorship
      of Health Planning].

PMID- 8159059
TI  - [Genetic therapy for cancer. Basics to understand it].

PMID- 8159060
TI  - [Syphilitic optic neuritis in 2 patients with HIV infection].

PMID- 8159061
TI  - [Incidence of malignant neoplasm of the cervix].

PMID- 8159062
TI  - [Sensitive syndrome as presentation form of anginose syndrome].

PMID- 8159063
TI  - [Factors facilitating changes in HIV risk behavior in parenteral drug users].

PMID- 8159064
TI  - [Hemichorea-hemiballismus syndrome worsened by haloperidol].

PMID- 8159065
TI  - [Analysts and microbiologists: cooperation].

PMID- 8159066
TI  - [Iron deficiency anemia caused by coffee ingestion].

PMID- 8159067
TI  - Fire--'good servant--bad master'.

PMID- 8159068
TI  - A psychiatric study of adult arsonists.
AB  - A series of 153 adult arsonists is described with particular reference to motives
      for fire-raising and psychiatric diagnosis. All had been referred for pretrial
      psychiatric reports and were assessed by routine clinical methods, supplemented
      where possible by the Personality Assessment Schedule. The series comprised
      mainly men, and most were relatively young, although these are also the
      characteristics of criminals in general. Most suffered from some form of mental
      disorder. Half of them had a personality disorder and a tenth were mentally
      handicapped. In addition to the mentally handicapped, a further 13 per cent had a
      history of special schooling, so that arsonists with some educational or learning
      difficulties made up a quarter of the total. Revenge was the most common motive,
      although present in only a third of the total, and the sexual element in
      motivation was much less common than appears to have been the case in the past.
      The motive of re-housing, not previously identified, was more common in women
      than in men. Almost two-thirds of the properties set on fire were domestic
      dwellings, and over a third of arsonists were intoxicated when they started the
      fires. Suggestions are made for further research focusing on personality
      characteristics which may be associated with fire-setting.

PMID- 8159069
TI  - Sudden infant death syndrome in Melbourne, Australia, 1987-1991.

PMID- 8159070
TI  - Pathological fire-setting 1951-1991: a review.
AB  - The purpose of this article is to review the whole literature on pathological
      fire-setting and related fields since 1951 in order to present a state of the art
      picture of our contemporary knowledge about this phenomenon. Papers were
      initially selected by using a Medline search. From the articles obtained in this
      way the references had to be pursued, because many relevant papers and books in
      this research field of different scientific and practical disciplines are not
      listed in conventional literature services. Finally, only those contributions
      were selected which provided new information when published, by original
      research, theoretical interpretation or practical implications. The last forty
      years have brought a growing body of data and understanding--especially
      concerning pathological fire-setting by children--etiology, and therapy, which
      often proves successful. The situation remains unclear for arson by
      psychologically disturbed adults and we still have a poor understanding of arson
      without apparent motive. There is a conflict of opinion as to whether adult fire
      setters are suitable for therapy and therapeutic efforts dealing with
      psychologically disturbed adults are rare. With increasing knowledge about child
      fire-setting and its successful treatment, etiological and therapeutic models for
      adult fire-setting behaviour may be developed. Research into the latter area
      should focus on both biographical and social conditions of development from
      childhood on as well as biological measures. Both will be reviewed here.

PMID- 8159071
TI  - Estimation of gestational age from hand and foot length.
AB  - Abortion, foeticide and infanticide have been practised from time immemorial by
      both primitive and civilized societies. Establishing the precise duration of
      gestation is an important point in the total medical evidentiary picture of
      infanticide. In this study, an attempt has been made to establish the gestational
      age of the foetus using foot and hand length. This study will be of help in
      establishing the gestational age when the foetus is fragmented. Results obtained
      were significant in establishing the gestational age.

PMID- 8159072
TI  - A modified stethoscope to assist in the identification of tooth coloured
      restorations.
AB  - Forensic odontologists are often called upon to assist in the identification of
      bodies. Since identification of the body relies on comparison of the post-mortem
      chart with the ante-mortem record it is important that all restorations present
      in the deceased's teeth are identified and correctly charted. If a restoration is
      present in an ante-mortem record then its absence in the post-mortem chart means
      that the two records cannot belong to the same person. However, tooth-coloured
      restorations can be difficult to identify, especially in the less than ideal
      conditions under which the odontologist may have to work. This study was designed
      to evaluate a simple technique for identifying tooth-coloured restorations,
      exploiting the difference between the surface roughness of restorative materials
      and that of the surrounding tooth substance. A conventional dental probe was
      substituted for the bell of a stethoscope. Differences in the surface texture of
      the tooth are reflected in changes in the sound heard by the examiner. The
      modified stethoscope is a useful and easily fabricated device, which may reduce
      the likelihood of small tooth-coloured restorations going unnoticed in post
      mortem examinations. The ability to detect fissure sealants using the device may
      also prove useful in epidemiological studies.

PMID- 8159073
TI  - Seclusion: an international comparison.
AB  - A review of the national and international literature on seclusion of psychiatric
      patients established its wide use throughout the countries located with use of
      primary or secondary published data. Although the form seclusion took varied
      considerably, with some embroiling the concept under the rubric of restraint, it
      became apparent that in the extremes of violence it was unavoidable. All the
      countries reviewed expressed concerns regarding the use of seclusion including
      the non-psychiatrized country highlighted, but were unable to provide a realistic
      practical alternative as an emergency measure.

PMID- 8159074
TI  - A follow-up of remanded mentally ill offenders given court hospital orders.
AB  - A follow up study of 101 men who were remanded to Brixton prison and who were
      given hospital orders by courts is reported. In 93% of cases the hospitals who
      responded to our enquiries reported that the admission had been appropriate. Only
      5 (11%) of the 46 men who had been discharged from hospital had absconded or
      discharged themselves without medical approval. The process of referral and
      admission to hospital resulted in these men having to spend, on average, between
      two and three times longer in custody when compared to men charged with similar
      offences. It is generally recognized that the acutely ill should not be
      imprisoned, and encouragement has been given to the diversion of such people from
      the Criminal Justice System. However, London presents particular problems in this
      respect and it is argued that, since such problems will always be present, there
      is a need for special psychiatric facilities to be opened in order to serve the
      needs of the Capital.

PMID- 8159075
TI  - Patterns of stab wounds: a six year study.

PMID- 8159076
TI  - Fettler's disease with smoke inhalation: particles within the lung.
AB  - In August 1985, a 72-year-old man died in the Manchester air disaster.
      Transmission electron microscopy of his lung tissue revealed not only inhaled
      smoke particles, but a large population of distinctive particles with different
      characteristics. These contain silicon and iron, as well as carbon and oxygen,
      and are thought to be related to his occupation as a fettler and to the extensive
      fibrosis seen on routine histology.

PMID- 8159077
TI  - Absent-mindedness and shop-lifting--a case study.
AB  - This article briefly reviews the literature describing the role of absent
      mindedness in shop-lifting. In addition, a case study is described which
      illustrates how a psychological formulation of such cognitive failures can aid
      the forensic clinician's understanding of shop-lifting.

PMID- 8159078
TI  - Diatoms and drowning--a cautionary case note.
AB  - A case is described in which, due to long-term repeated exposure to the same body
      of diatom-containing water, comparable diatom findings in the tissues and
      environmental samples were not acceptable as proof of drowning. A commonly
      overlooked pitfall limiting the value of acid-digestion in marine cases is
      emphasized.

PMID- 8159079
TI  - Sudden cardiac ischaemic death associated with systemic lupus erythematosus.
AB  - Association between systemic lupus erythematosus and coronary atherosclerosis has
      been reported only rarely in the medical literature. Sudden ischaemic cardiac
      death in such cases is an uncommon terminal event, particularly in young
      patients. The severity of coronary atherosclerosis in these cases may be similar
      to those seen in the classic coronary disease. A case of a 22-year-old female
      systemic lupus patient is presented in whom sudden death was found at autopsy to
      be due to extensive coronary atherosclerosis.

PMID- 8159080
TI  - Anabolic steroids--the drugs that give and take away manhood. A case with an
      unusual physical sign.
AB  - A case is presented in which the abuse of anabolic steroids by a body builder led
      to an unusual physical sign. The case discusses the effects that anabolic steroid
      abuse can have upon manhood. The frequency of anabolic steroid misuse is
      increasing. The implications of this with respect to psychiatric illness and
      violent crime are discussed. It is well known that the use of anabolic steroids
      among young men, body builders in particular, is growing apace (Perry and
      Littlepage, 1992), and they may be aware of the risks of impurity and
      contamination. There is a wide range of anabolic steroids in use; they are often
      used in doses of greater than 1 mg/kg per day. As well as single use, the misuser
      may 'stack' (use more than one at a time) or 'pyramid' (use increasing doses of a
      given drug) the steroids (Kennedy, 1990). The physical and psychiatric effects of
      anabolic steroids are well known (Kashkin and Kleber, 1989; Brower, 1992; Pope
      and Katz, 1988). However, we describe a case with psychiatric symptoms, a violent
      outburst and a unique (?) physical sign.

PMID- 8159081
TI  - Diabetic death bed: post-mortem determination of hypoglycaemia.
AB  - The post-mortem biochemical determination of hypoglycaemia in the practice of
      forensic medicine is notoriously imprecise and attracts perennial criticisms,
      particularly from those who may be alien to the peculiarities of medical
      jurisprudence. There has been re-emphasis recently on the neuropathological
      pathoclisis ascribed to prolonged hypoglycaemia. Unfortunately, the value
      perceived is limited by pathognomonic unreliability owing to agonal
      multifactorial influences and rapidly fatal nocturnal hypoglycaemia. The
      predicament is oppressive to a consideration of preponderant evidence and an
      unpopular diagnosis of peri-mortem hypoglycaemia, unless audacious, may be
      precluded simply because the proof is difficult. This is likely to contribute to
      diagnostic under-estimation of enigmatic diabetic deaths. A suspected case of
      lethal nocturnal hypoglycaemia in a young diabetic on 'animal' insulin is
      presented to restore some perspective to the clinico-pathological deference for
      an endangered post-mortem diagnosis of hypoglycaemia inferred from minimal
      evidence.

PMID- 8159082
TI  - [Toxic effects of lead in children].
AB  - Children belong to this group of population which is most sensitive to harmful
      effect of lead. The neurotoxic effect of lead in children is assessed by means of
      psychological tests. They allow to evaluate general intellectual development,
      specific abilities and behavioural features. The author discussed the results
      (available in literature) of clinical examinations of children with higher blood
      level of lead found during blood tests performed for other purposes: cross
      sectional epidemiological studies covering children exposed to lead in the place
      of their residence; and prospective studies of children followed up since birth
      in view of their exposure to lead and health effects caused by this exposure. The
      relationship between the level of exposure and psychological deficiency is rather
      low (exposure to lead explains from 1 to 4% of psychological variables variance),
      however, in a number of studies this relationship proved to be statistically
      significant. Taking into account the prospective studies it should be presumed
      that the blood lead level from 10 to 15 micrograms/dl may produce a risk of the
      developmental deficiency in an early childhood.

PMID- 8159083
TI  - [Exposure to lead in the Silesian region].
AB  - The work is based on the determination of blood lead levels performed by the
      Central Laboratory of Toxicology of Heavy Metals in workers employed in various
      plants in the Katowice voivodship. The method of atomic absorption (ASA) was used
      for the determination. The Laboratory has participated successfully in the inter
      laboratory programme of quality assurance. The study revealed that the highest
      exposure to lead occurs in overhaul and dismantle plants (group II) which work
      for large industrial establishments of non-ferrous metals (group I). Among
      establishments of group I higher exposure was found in raw material departments.
      Workers of certain professions such as fitters, refiners, smelters are
      particularly exposed regardless of the production profile of plants. The blood
      lead level is an important marks of occupational exposure to lead. Examinations
      should be performed only by laboratories involved in the programme of quality
      assurance of laboratory measurements.

PMID- 8159084
TI  - [Biological monitoring of lead: system and quality control].
AB  - The assessment of health effects of lead exposure is based on the determination
      of lead blood concentrations. The correctness of predicting these effects depends
      on the reliability of determination results. The latter can be confirmed only if
      the laboratory participates in the quality assurance programme for chemical
      analyses. The aim of the present study was to investigate the systems in use for
      quality control, methods of determining lead blood concentration and the results
      of a project on quality control for lead determination in Poland (project
      coordinated by the Nofer Institute of Occupational Medicine, Lodz, Poland). The
      paper discusses the principles of the quality assurance programme implemented in
      Poland, elements of good laboratory practice with respect to blood sampling,
      analytical equipment and the use of flameless AAS for determining lead blood
      concentration. The quality assurance programme for lead determinations covers
      nine laboratories. The initial stage of its implementation revealed that only 50%
      of the determinations were correct. Consequently, a series of audits was made at
      the laboratories and some training provided for the staff. The last round
      indicated an increase in the percentage of correct results of up to 80%. Proper
      performance of lead determinations carried out routinely for the assessment of
      industrial exposure to lead is of extreme importance in view of the fact that
      lead determinations in blood are planned to be made compulsory and to replace
      urinary determinations of the metal.

PMID- 8159085
TI  - [Biological levels of lead in residents of Poland].
AB  - The author discussed current data on sources of the environmental exposure to
      lead, health effects of exposure in adults and children as well as recommended
      admissible concentrations of lead in blood. The review of studies on biological
      monitoring of exposure to lead in Poland permits to state that the results of
      measurements of Pb-B concentrations performed by laboratories which did not
      participate in the inter-laboratory programme of quality assurance were often
      overestimated evoking public concern. The outcome of investigations carried out
      by the Nofer Institute of Occupational Medicine in Lodz and other institutions
      which are provided with appropriate analytical equipment, tested under the inter
      laboratory programme of quality assurance gives the ground for a hypothesis that
      an excessive environmental exposure to lead in Poland may result only from
      industrial emission. The mean geometric lead blood concentrations in persons
      living in areas free from industrial emissions of lead range from 40 to 70
      micrograms/l and they do not prove any potential hazard for adults. Exposure of
      children and pregnant women living in areas polluted with lead due to industrial
      emissions and where mean geometric Pb-B concentrations reach 100-170 micrograms/l
      may create a significant problem. The results obtained emphasize the need for
      targetted surveillance aimed at identifying areas of excessive lead
      contamination, measurements of Pb-B concentrations in populations living in those
      areas and necessary preventive measurements. Collection of blood samples and
      measurements of lead levels should be performed only by those laboratories which
      satisfy necessary requirements.

PMID- 8159086
TI  - [Editorial].

PMID- 8159087
TI  - [Lead hazards in Polish industry].
AB  - The author presented information of 1988 on occupational exposure to lead in the
      Polish industry and discussed more thoroughly current data applying to the
      Katowice voivodship. The incidence of lead poisoning in various branches of the
      national economy in recent ten years was also discussed. A decreasing tendency in
      the frequency of this disease has been observed. Amendments to principles of
      diagnosis and prevention of lead poisoning were proposed as well as
      classification of health effects of exposure to lead and medical certification.

PMID- 8159088
TI  - [Evaluation of lead sampling from food products].
AB  - Lead is recognised as an element most harmful to human health. Food is the main
      source of human exposure to lead. The level of this element in foodstuff is
      limited by the national and international legal regulations. The level of lead
      was determined in daily diet of children and youngsters as well as in selected
      agricultural products (vegetables, potatoes, fruit, cereals), flour, bakery
      products and children foods. Samples of agricultural products were collected from
      regions which were not directly contaminated by industrial plants and motor
      transport (20 voivodships). Altogether 1700 meals were analysed, about 2500
      samples of vegetables, 1023 of fruit, 919 of cereals and 676 of other foodstuffs.
      It was revealed that mean intake of lead among adults was lower than the
      provisional tolerable weekly intake (PTWI) compulsory at that time, while in
      small children PTWI values were exceeded in 6 out of 10 voivodships investigated.
      On the ground of these results certain changes were suggested or already made in
      the national legislation concerning the admissible level of lead.

PMID- 8159089
TI  - [Report of the Toxicologic Commission of the Sanitary and Epidemiologic Council.
      General evaluation of toxicologic hazards caused by lead in Poland].

PMID- 8159090
TI  - [Lead in the environment of Poland].
AB  - Lead belongs to those elements which have a great variety of applications in the
      up-to-date technology. In the form of waste products or automotive wastes it has
      been brought into a global circulation. The authors attempt to present harmful
      effects of this "environmental poison" on individual media and human population
      in Poland. Following published and non-published data, an outline of lead
      geochemistry, anthropo-genetic sources of lead emission into the environment,
      concentration of lead in the ambient air, surface water, soil, plants and food,
      is presented. The data are interpreted on the basis of home maximum allowable
      concentrations and on the health criteria recommended by international
      organizations. It was found that the knowledge on the level of pollution of
      individual environmental media with lead is diversified and incomplete. This
      hinders a comparable and comprehensive evaluation of lead migration in the
      natural environment and thus the assessment of exposure magnitude among
      inhabitants of all regions (voivoships) of the country. Emissions from plants
      producing and processing non-ferrous metals, industrial waste sites, motor
      transport especially in central parts of urban and industrial agglomerations, and
      use of certain mineral fertilizers are recognized as the greatest hazards to the
      biosphere and human health among all sources of environmental pollution with
      lead. As appears from the data, the highest level of lead contamination of air,
      water and soil occurs in the central part of the Upper Silesian Industrial
      District as well as in the direct vicinity of other plants of non-ferrous metals
      in Katowice and Legnica voivodships. It was also noted that crops from those
      agglomerations and from family gardens located near active industrial waste sites
      or exploited yards may contain amounts of lead exceeding considerably allowable
      concentrations. It was revealed that in Polish conditions the largest amounts of
      lead enter children's organism with dirt, dust and food and the smallest with
      water. Vegetables and potatoes, and in the case of children, milk as well are the
      main carriers of lead in Polish food, therefore, these products should remain
      under particular laboratory control. It is acknowledged that preventive measures
      in areas where the level of environmental pollution with lead is not fully
      recognized, biological monitoring of lead concentrations in the blood of
      children, the most sensitive group of population, should be initiated.

PMID- 8159091
TI  - [Reference levels of lead in children from clean regions of Poland].
AB  - Following the determination of blood lead levels in children of 8-10 age group,
      living in selected clean regions of Poland, a statistical analysis of results was
      carried out. On the basis of this analysis reference values were proposed. The
      values are characteristic for the whole area of Poland and they should be applied
      in all studies pertaining to the assessment of exposure to lead among children. A
      border concentration of lead in blood equal to 14 micrograms/dl was proposed as a
      reference one for individual examinations. For group examinations reference
      concentrations of 50 and 90 percentiles should not exceed 8 micrograms/dl and 12
      micrograms/dl, respectively.

PMID- 8159092
TI  - [Monitoring biological lead in Silesian populations with particular reference to
      elementary school children].
AB  - The national production of lead is concentrated in the Katowice region
      (voivodship). Another harmful factor observed in this area is a high intensity of
      motor transport. Hence, high contamination of air and surface layers of soil,
      particularly in the Upper Silesian Industrial District. The main objective of
      this work was to review the results of surveys of lead concentrations in the
      blood (Pb-B) of children and adults living in this area. The presented results of
      biological monitoring of lead were obtained from cohort, prospective and cross
      sectional studies of groups of primary school children and their mothers, carried
      out by the Regional Sanitary and Epidemiological Station during the years 1981
      1990 (N = 4570) as well as from examinations performed in 283 children (1-15 age
      group) by the Silesian Medical Academy and in 1028 children (1st and 8th grades
      of school) by the Institute of Environmental Protection. The concentration of
      lead was measured in samples of venous blood using atomic absorption
      spectrophotometry. The Regional Sanitary and Epidemiological Station Laboratory
      involved in Pb-B measurements has successfully participated in the
      interlaboratory programme of quality assurance. The results indicated that the
      contamination of the environment with lead in the Katowice region is very much
      diversified, and, in general, three areas can be identified: 1. The vicinity of
      large industrial emissions of lead, where mean Pb-B concentrations were usually
      twice as high as in rural areas of the Katowice voivodship. In many cases the
      lead blood concentrations exceeded the safe limit of 19 micrograms/dl and the
      excess varied in time. 2. Large industrial urban agglomerations of the Upper
      Silesian Industrial District. The Pb-B concentrations in children living in this
      area were higher by 50% in comparison with rural areas. The excess of safe limit
      (19 micrograms/dl) was, however less frequent that in the area described above.
      3. Rural areas. But even in those areas not all Pb-B concentrations were fully
      acceptable. A continuous biological monitoring of lead in representative samples
      of the population living in this area is necessary to obtain completely reliable
      assessment of exposure to lead in the Katowice voivodship.

PMID- 8159093
TI  - Evidence of non-deficient low-density lipoprotein receptor patients in a pool of
      subjects with clinical familial hypercholesterolemia profile.
AB  - For this study, we selected 41 adult patients with the classic clinical diagnosis
      of heterozygous familial hypercholesterolemia (FH), which is characterized by a
      low-density lipoprotein (LDL) cholesterol level above the 95th percentile,
      xanthomas, and/or personal or familial cardiovascular history. We used an
      indirect immunocytofluorimetric assay to classify these 41 subjects according to
      LDL receptor function on lymphocytes. We found that LDL receptor activity was
      normal in nine patients. A large study of plasma lipid, lipoprotein, and
      apolipoprotein levels found no significant difference between patients with and
      without LDL receptor defect. Familial defective apolipoprotein (apo) B-100 (FDB)
      and LDL-binding defects were not found in the nine patients without LDL receptor
      defect. These results suggest that other defects in the regulation of lipoprotein
      metabolism are capable of giving rise to a clinical and biochemical disorder
      indistinguishable from classic FH.

PMID- 8159094
TI  - Uremia-induced disturbances in hepatic carbohydrate metabolism: enhancement by
      sucrose feeding.
AB  - A high-sucrose (S) diet accentuates anorexia and stunts growth in uremic (U)
      rats, and an oral S load induces a greater hyperfructosemia in U rats than in
      control (C) rats. Four studies were performed to determine the roles of S feeding
      and an acute S load on liver carbohydrate (CHO) metabolism in U and C rats (eight
      to 10 rats per group). We also examined the plasma responses to either water or a
      S load. Levels of the main metabolites of glycolysis, gluconeogenesis, and
      glycogenesis were measured under basal conditions (7 hours' postmeal) in U and C
      rats fed either a cornstarch diet (study I) or S diet (study II) and at 30 and 60
      minutes after an intragastric S load (studies III and IV) in s-fed U and C rats.
      The weight gain, food intake, and plasma creatinine and urea levels of the rats
      in the four studies were comparable. Weight gain and liver weight (g/100 g body
      weight) were lower in U than in C rats. In the plasma, baseline levels of lactate
      were decreased by uremia and S feeding and those of glucose (G) were increased by
      S feeding. The increases in plasma G and fructose (F) levels after a S load were
      greater in U rats than in C rats, whereas those of plasma lactate were
      comparable. In the liver under basal conditions, uremia markedly decreased levels
      of glycogen, F-1,6-diphosphate (F-1,6-diP), F-2,6-diP, 3-glycero-phosphate (3
      glycero-P), dihydroxyacetone phosphate (DHAP), pyruvate, lactate, and adenosine
      triphosphate (ATP), and the phosphorylation state (ATP/adenosine diphosphate
      [ADP] x inorganic phosphorus [PI]), increased phosphoenolpyruvate (PEP), ADP, and
      Pi levels, but did not affect the cytosolic redox state (pyruvate/lactate). In
      addition to uremia, S feeding further decreased levels of glycogen, F-2,6-diP, 3
      glycero-P, and ATP. After S loading, liver F levels increased more in U than in C
      rats, but glycogen and 3-glycero-P levels increased less in U than in C rats.
      Liver lactate and pyruvate levels increased more in U than in C rats, and the
      pyruvate/lactate and DHAP/3-glycero-P ratios were higher in U than in C rats
      after a S load. The ATP level and the phosphorylation state in U rats increased
      30 minutes later in U than in C rats. Our findings indicate that uremia causes a
      depletion in liver glycogen, which is enhanced by S feeding and could be
      partially attributed to decreased glycogen synthesis.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8159095
TI  - Effect of high-protein meal plus aspartame ingestion on plasma phenylalanine
      concentrations in obligate heterozygotes for phenylketonuria.
AB  - The effect of a protein-rich meal alone or in combination with 85 mumol/kg body
      weight aspartame (APM) on plasma phenylalanine and large neutral amino acids
      (LNAA) was evaluated in obligate heterozygotes for phenylketonuria (PKU) and
      normal subjects (controls). Thirteen PKU heterozygotes (seven women, six men) and
      13 controls (five women, eight men) ingested a 12-noon meal providing
      approximately 303 mumol/kg Phe. In addition, 10 PKU heterozygotes (five women,
      five men) and 10 controls (five women, five men) ingested the same meal with 85
      mumol/kg APM (providing 75 mumol/kg Phe). Plasma amino acids were analyzed at
      baseline (-4 and 0 hours) and at 1, 3, and 20 hours after the meal or meal plus
      APM. Compared with the meal alone, ingestion of the meal plus APM significantly
      increased plasma Phe concentrations in both controls and PKU heterozygotes. Mean
      plasma Phe values were higher for controls at 1 hour (95 +/- 7 mumol/L) and for
      PKU heterozygotes at 3 hours (153 +/- 21 mumol/L). After the addition of APM to
      the meal, the highest mean plasma Phe concentration was only slightly greater
      than the usual postprandial range for both controls and PKU heterozygotes.
      Ingestion of the meal did not increase the plasma Phe/LNAA ratio in either
      controls or PKU heterozygotes. Compared with baseline, the plasma Phe/LNAA ratio
      increased significantly 1 hour after combined ingestion of the meal plus APM in
      both groups (P = .020 and P = .008, respectively); however, the ratios were well
      below the range of Phe/LNAA values in individuals with mild
      hyperphenylalaninemia, who are clinically normal and do not require a Phe
      restricted diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159096
TI  - The four-compartment models in body composition: data from a study with dual
      energy X-ray absorptiometry and near-infrared interactance on 815 normal
      subjects.
AB  - With the aim of studying body composition according to a four-compartment model
      in different age groups of healthy subjects, total body water (TBW), body fat
      (BF), lean body mass (LBM), and total-body bone mineral content (TBBMC) were
      estimated with dual-energy x-ray absorptiometry (DEXA) and near-infrared
      interactance in 308 normal males and 507 normal females aged 15 to 83 years.
      Subjects were divided into 5-year groups up to the age of 50, and then into 10
      year groups. In both sexes, BF showed a positive correlation with age (P < .001)
      and was higher in females aged 40 to 44 compared with younger groups. LBM
      decreased with age only among males (P < .05). A similar finding was observed
      with TBW. TBBMC values did not differ between sexes in the 15- to 19-year-old
      group, and were greater in males in the remaining age groups. This parameter did
      not vary among females until menopause, and decreased in the 50- to 59-year-old
      group (P < .001) and from the age of 60 onward (P < .001). Height decreased (P <
      .001) and weight increased with age (P < .001). Both in male and female groups
      height and weight correlated with TBBMC (P < .001). When corrected for weight,
      TBBMC did not vary except in men older than 50, who showed lower values (P <
      .005). When corrected for height, TBBMC only changed in women aged 30 to 34 and
      35 to 39.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159097
TI  - Relationship between hemorrheologic factors and insulin sensitivity in healthy
      young men.
AB  - The present study aimed at testing a possible relationship between hemorrheologic
      factors, such as hematocrit, fibrinogen, and whole-blood viscosity, and insulin
      sensitivity in healthy humans. Twenty-one 21-year-old men were studied with the
      hyperinsulinemic euglycemic glucose clamp technique. We found statistically
      significant negative correlations between the glucose disposal rate (GDR) and
      calculated whole-blood viscosity at both high (r = -.55, P = .01) and low (r = 
      .51, P = .01) shear rates. We observed negative associations between GDR and
      fibrinogen (r = -.66, P = .002), GDR and hematocrit (r = -.63, P = .002), GDR and
      body mass index (r = -.51, P = .007), and GDR and resting heart rate (r = -.46, P
      = .04). Using stepwise multiple regression considering whole-blood viscosity,
      body mass index, mean arterial blood pressure, and heart rate as independent
      variables, we found that only whole-blood viscosity and body mass index were
      independent explanatory variables of the GDR. Together they accounted for 63% of
      the variability in the GDR in our subjects. These results suggest hemorrheologic,
      and therefore indirectly hemodynamic, factors as correlates to insulin
      sensitivity.

PMID- 8159098
TI  - Effects of glucose and amino acid infusion on glucose turnover in insulin
      resistant obese and type II diabetic patients.
AB  - Glucose turnover was assessed from [6,6-2H]glucose and [U-13C]glucose dilution
      analysis in six lean nondiabetic subjects, six obese patients with normal glucose
      tolerance, and six obese patients with non-insulin-dependent diabetes mellitus
      (NIDDM) during sequential infusions of glucose (13.9 mumol/kg fat-free mass
      [FFM]/min) and glucose+amino acid (4.2 mg/kg FFM/min). Cori cycle activity was
      assessed from the difference between glucose turnover obtained from [6,6
      2H]glucose and [U-13C]glucose. During infusion of glucose alone, total glucose
      turnover was increased by 70% in obese NIDDM patients. Amino acid infusion
      decreased glucose concentrations by 0.8, 0.5, and 1.8 mmol/L in controls, obese
      patients, and NIDDM patients, respectively. This decrease in glycemia occurred
      despite an increase in glucose turnover in lean and obese nondiabetic subjects,
      and was due to an increased metabolic clearance rate (MCR) of glucose. In NIDDM
      patients the MCR of glucose was unchanged, and the decrease in glycemia was
      explained by a diminution in hepatic glucose output. Glucose turnover obtained by
      [6.6-2H] dilution analysis exceeded significantly the values obtained by dilution
      analysis in obese subjects and obese NIDDM patients, but not in controls. This
      indicates an increased Cori cycle activity in these patients.

PMID- 8159099
TI  - Adenosine triphosphate release by osmotic shock and hemoglobin A1C in diabetic
      subjects' erythrocytes.
AB  - We investigated the significance of adenosine triphosphate (ATP) release from
      diabetic subjects' red blood cells (RBCs) following osmotic shock (OS) and its
      possible relationship with hemoglobin A1C (HbA1C) and with the RBC membrane
      protein skeleton. RBCs from type I (insulin-dependent [IDDM]) and type II (non
      insulin-dependent [NIDDM]) diabetic subjects and age- and sex-matched control
      subjects were submitted to OS using NaCl solutions (from 0.9% to 0.045% final
      concentration). ATP release values were determined by the bioluminescent method.
      For pattern study, they were expressed both as absolute values and as percentages
      (%) of ATP maximum release (at 0.045% NaCl solution). Twenty-seven IDDM and 25
      NIDDM subjects and two control groups were investigated. ATP content in RBCs was
      2.08 +/- 0.19 pmol/10(4) RBC in IDDM and 1.23 +/- 0.20 pmol/10(4) RBC in NIDDM
      subjects. The ATP content of IDDM subjects' RBCs was significantly higher than
      that of the corresponding control group. ATP release at 0.49% NaCI OS, both as
      absolute value and as percentage value, was significantly lower in both diabetic
      groups, and ATP% was inversely correlated with HbA1" (IDDM: r = -.489, P < .01;
      NIDDM: r = -.654, P < .01), suggesting a possible relationship between Hb
      glycation, RBC membrane protein skeleton glycation, and its influence on ATP
      release by OS. In conclusion, the proposed method seems useful for measuring RBC
      ATP content and, at the same time, for monitoring the leak effect of the RBC
      membrane before it bursts.

PMID- 8159100
TI  - Differential effect of insulin on whole-body proteolysis and glucose metabolism
      in normal-weight, obese, and reduced-obese women.
AB  - The whole-body rate of proteolysis, as indicated by the postabsorptive appearance
      rate (Ra) of leucine, is increased in obese women. The present study was
      conducted to examine the hypothesis that the increased proteolysis is explained
      by insulin resistance, and to determine if proteolysis returns to normal when
      obese women reduce to normal weight. The mean basal leucine Ra was 21% higher in
      31 obese women (> 135% ideal weight) than in 17 normal-weight women, and 9%
      higher per kilogram lean body mass ([LBM] P > .05). When 17 of the obese women
      reduced and stabilized at 100% to 116% of ideal weight, their mean basal leucine
      Ra decreased 17% (7%/kg LBM) and was not significantly different from that of the
      normal-weight control group. Insulin (40 mU/m2/min) was infused for 2 hours while
      maintaining euglycemia in eight normal-weight, 14 obese, and eight reduced-obese
      subjects. Glucose disposal per kilogram LBM was 29% lower in obese than in normal
      weight subjects (P < .05) and was normal in the reduced-obese subjects. Insulin
      suppressed the leucine Ra an average of 18.4% in the control group, 20.4% in the
      obese group, and 24.1% in the reduced-obese group. Suppression of the leucine Ra
      by insulin did not correlate with the waist to hip ratio (WHR), glucose disposal
      rate, or basal leucine Ra. We conclude that the increased basal proteolysis of
      obese women is reversed by weight loss, and is not caused by insulin resistance.

PMID- 8159101
TI  - Insulin propeptides in conditions associated with insulin resistance in humans
      and their relevance to insulin measurements.
AB  - Routine insulin assays measure not only biologically active insulin but also the
      relatively inactive propeptides, proinsulin and desdipeptide proinsulin. Such
      measurements may be misleading if insulin propeptide levels are increased, as has
      been reported in patients with non-insulin-dependent diabetes mellitus (NIDDM).
      Inferences regarding insulin resistance, based on hyperinsulinemia, could thus be
      invalidated where routine insulin assays have been used. We have measured plasma
      insulin levels using a routine assay, together with measurements of the major
      circulating insulin propeptides, intact proinsulin and des 31,32proinsulin, in
      various clinical situations associated with apparently increased insulin levels
      and insulin resistance. Major increases of insulin propeptide levels relative to
      insulin levels were not seen in obese subjects or in patients taking oral
      contraceptives or danazol, or in obese subjects compared with non-obese controls.
      Although the insulinemic responses observed with routine radioimmunoassay in
      these situations associated with insulin resistance are not confounded by major
      changes in the proportion of circulating insulin propeptides, further studies
      will be necessary to validate investigations in other insulin-resistant states.

PMID- 8159102
TI  - Diabetes increases hepatic hydroxymethyl glutaryl coenzyme A reductase protein
      and mRNA levels in the small intestine.
AB  - Previous studies have shown that both cholesterol synthesis and the activity of
      hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase, the rate-limiting
      enzyme in cholesterol synthesis, are increased in the small intestine of a wide
      variety of different animal models of diabetes. In the present study, we
      demonstrate that the mass of HMG CoA reductase protein is increased in the small
      intestine of both streptozocin-induced diabetic rats (2.5-fold) and
      streptozocin/alloxan-induced diabetic dogs (2.4-fold). These increases in HMG CoA
      reductase protein mass are of a magnitude similar to the previously observed
      increases in either HMG CoA reductase activity and/or cholesterol synthesis in
      the small intestine of diabetic animals. Furthermore, mRNA levels for HMG CoA
      reductase in the small intestine of diabetic rats and diabetic dogs are increased
      2.1- and 1.7-fold, respectively. These results suggest that the increase in HMG
      CoA reductase protein levels in the small intestine of diabetic animals is due to
      an increase in mRNA levels. In contrast, mRNA levels for HMG CoA reductase in the
      liver of diabetic rats are not increased. Additionally, mRNA levels for the low
      density lipoprotein (LDL) receptor are also increased in the small intestine of
      diabetic animals (rats, 43%; dogs, 59%). The increase in small-intestinal
      cholesterol synthesis has the potential for adversely affecting lipoprotein
      metabolism and increasing the risk of atherosclerosis in diabetes.

PMID- 8159103
TI  - Treatment with a beta-blocker with beta 2-agonism improves glucose and lipid
      metabolism in essential hypertension.
AB  - In a randomized double-blind crossover study in 42 patients with essential
      hypertension, the metabolic effects of a beta-adrenergic blocker with a
      pronounced beta 2-agonistic effect, dilevalol 400 mg x 1, were compared with
      those of metoprolol succinate 200 mg x 1. The effects of glucose metabolism were
      evaluated by the hyperinsulinemic euglycemic clamp technique and an intravenous
      glucose tolerance test (IVGTT). Insulin-mediated glucose disposal (M) and the
      insulin sensitivity index (M/I) increased by 19% (P = .011) and 10% (P = .27),
      respectively, during dilevalol treatment, but decreased by 10% (P = .15) and 22%
      (P = .0025), respectively, during metoprolol treatment, giving rise to
      significant differences between the two treatment regimens. Compared with
      dilevalol-treated patients, those treated with metoprolol showed increased plasma
      insulin values at the end of the IVGTT, but there was no difference in plasma
      glucose concentrations or glucose tolerance. Hemoglobin A1c (HbA1c) levels
      increased by 5.4% (P = .04) in the metoprolol group. Serum cholesterol, total
      serum and very-low-density lipoprotein (VLDL) triglycerides, and serum urate
      levels decreased significantly (by 6%, 22%, 29%, and 14%, respectively) during
      dilevalol treatment, and there was a significant difference between the effects
      of the two drugs on total, VLDL, and low-density lipoprotein (LDL) triglyceride
      and serum urate levels. These data demonstrate that a beta-blocker with a partial
      beta 2-agonist action differs in its metabolic effect profile from a selective
      beta 1-blocker and may offer advantages by improving glucose and lipid
      metabolism.

PMID- 8159104
TI  - Effects of dietary protein restriction on glucose and insulin metabolism in
      normal and diabetic humans.
AB  - We determined whether the amount of protein in the diet can affect insulin
      requirements in subjects with diabetes mellitus and glucose metabolism in normal
      subjects. Seven normal-weight volunteers with uncomplicated, intensively
      controlled, type I (insulin-dependent) diabetes and 12 similar nondiabetic
      subjects were studied on a metabolic ward before and after consuming a
      maintenance-energy but protein-free diet for 10 days. Blood glucose levels of
      diabetic subjects were measured seven times daily in response to insulin
      administration by continuous subcutaneous infusion. The plasma glucose appearance
      rate (Ra) was measured in seven normal subjects and all diabetic subjects using a
      primed-continuous infusion of D-[6,6-2H2]glucose. After adaptation to the protein
      restricted diet, diabetic subjects experienced a 30% decrease in average
      preprandial and average daily blood glucose concentrations (P < .01); this
      occurred despite a concurrent 25% decrease in both basal and bolus insulin
      dosages (P < .001). Protein restriction decreased the postabsorptive glucose Ra
      (P < .05) and insulin concentrations (P < .01) of normal subjects by 20%, and
      increased their fasting glucagon concentrations by 24% (P < .01). We conclude
      that severe protein restriction decreases insulin requirements in type I diabetes
      and fasting hepatic glucose output and basal insulin levels in normal subjects.
      This effect appears to be mediated in part by decreased hepatic gluconeogenesis,
      but a contributory influence of increased insulin sensitivity is not ruled out.

PMID- 8159105
TI  - Reversal of severe osteoporosis with vitamin B12 and etidronate therapy in a
      patient with pernicious anemia.
AB  - Pernicious anemia has recently been recognized as a risk factor for osteoporosis
      and fractures. Although vitamin B12 is important for osteoblast function, the
      effect of vitamin B12 replacement in states of vitamin B12 deficiency on bone
      density and fracture incidence is not known. We report 2-year follow-up data from
      a patient with severe osteoporosis, multiple vertebral compression fractures, and
      pernicious anemia who exhibited a dramatic response to treatment with vitamin B12
      and cyclic etidronate. Serial bone density measurements demonstrated a 15% and
      17% increase in the lumbar and greater trochanter regions, respectively, and a
      79% increase in the femoral neck region over the 2-year follow-up period. In
      addition to normalization of bone density compared with age-matched controls, no
      subsequent vertebral fractures were noted in the 2-year period following
      initiation of vitamin B12 and etidronate therapy. This case demonstrates that
      osteoporosis associated with pernicious anemia may be markedly improved by
      vitamin B12 replacement and cyclic etidronate therapy.

PMID- 8159106
TI  - Relationship between obesity and serum lipoproteins in children with different
      apolipoprotein E phenotypes: the Bogalusa Heart Study.
AB  - The influence of apolipoprotein (apo) E polymorphism on the association between
      body fatness and concentrations of serum lipoprotein variables was studied in a
      random subsample (n = 892) of 8- to 17-year-old children from a total community.
      Covariates (age, race, and sex)-adjusted mean values of percent body fat,
      ponderal index (wt/ht3), and subscapular skinfold thickness differed
      significantly among apo E phenotype groups, with the apo E2 group (n = 61)
      carrying E2/2 and E3/2 phenotypes having significantly (P < .01) lower values
      than the apo E3 group (n = 480) carrying the E3/3 phenotype. In the apo E3 group,
      covariates-adjusted partial correlation coefficients showed significant (P < .05
      to P < .001) associations between obesity measures and lipoprotein variables
      studied that are generally seen in populations. However, these associations, with
      the exception of low-density lipoprotein (LDL) cholesterol and apo B, were
      altered in the other apo E phenotype groups. In the apo E2 group, obesity
      measures correlated significantly with triglycerides (P < .05 to P < .001), but
      not with very-low-density lipoprotein (VLDL) cholesterol, high-density
      lipoprotein (HDL) cholesterol, and apo A-I. In contrast, in the apo E4 group (n =
      212) carrying E4/3 and E4/4 phenotypes, obesity measures correlated significantly
      with HDL cholesterol (P < .05 to P < .001) and apo A-I (P < .01), but not with
      triglycerides and VLDL cholesterol. Therefore, the apo E phenotype should be
      taken into account in the association between body fatness and serum
      lipoproteins.

PMID- 8159107
TI  - Effects of tumor necrosis factor-alpha on glucose and albumin production in
      primary cultures of rat hepatocytes.
AB  - Tumor necrosis factor-alpha (TNF) is known to alter significantly in vivo hepatic
      glucose and albumin metabolism. However, it remains unclear whether the observed
      effects represent direct actions of this factor or secondary responses due to the
      recruitment of other mediator systems. The present study was designed to
      investigate direct actions of TNF on glucose and albumin production in primary
      cultures of rat hepatocytes. Addition of TNF to the culture medium resulted in a
      45% to 50% reduction in glucose production from a control level of 239 +/- 15
      nmol/plate.h. This effect was reversed by addition of anti-TNF monoclonal
      antibody. In glycogen-depleted cells, short-term (5-hour) incubation with TNF did
      not affect hepatocyte albumin secretion, which was 8.13 +/- 0.29
      microgram/plate.h. However, in cells exposed to insulin or in non-glycogen
      depleted cells, addition of TNF resulted in a 10% to 25% reduction in albumin
      production. These findings indicate that TNF exerts direct inhibitory effects on
      hepatocyte glucose and albumin production, but the effects on the latter process
      are modest. A notable aspect of the findings is that the albumin effects are
      insulin or glucose substrate-dependent, which may have implications regarding
      liver function during nutritional support in critical illness.

PMID- 8159108
TI  - Whole-body energy metabolism and skeletal muscle biochemical characteristics.
AB  - A low metabolic rate for a given body size and a low fat versus carbohydrate
      oxidation ratio are known risk factors for body weight gain, but the underlying
      biological mechanisms are poorly understood. Twenty-four-hour energy expenditure
      (24EE), sleeping metabolic rate (SMR), 24-hour respiratory quotient (24RQ), and
      forearm oxygen uptake were compared with respect to the proportion of skeletal
      muscle fiber types and the enzyme activities of the vastus lateralis in 14
      subjects (seven men and seven women aged 30 +/- 6 years [mean +/- SD], 79.1 +/-
      17.3 kg, 22% +/- 7% body fat). The following enzymes were chosen to represent the
      major energy-generating pathways: lactate dehydrogenase (LDH) and
      phosphofructokinase (PFK) for glycolysis; citrate synthase (CS) and beta
      hydroxyacl-coenzyme A dehydrogenase (beta-OAC) for oxidation; and creatine kinase
      (CK) and adenylokinase (AK) for high-energy phosphate metabolism. Forearm resting
      oxygen uptake adjusted for muscle size correlated positively with the proportion
      of fast-twitch muscle fibers (IIa: r = .55, P = .04; IIb: r = .51, P = .06) and
      inversely with the proportion of slow oxidative fibers (I: r = -.77, P = .001).
      24EE and SMR adjusted for differences in fat-free mass, fat mass, sex, and age
      correlated with PFK activity (r = .56, P = .04 and r = .69, P = .007,
      respectively). 24RQ correlated negatively with beta-OAC activity (r = -.75, P =
      .002). Our findings suggest that differences in muscle biochemistry account for
      part of the interindividual variability in muscle oxygen uptake and whole-body
      energy metabolism, ie, metabolic rate and substrate oxidation.

PMID- 8159109
TI  - Plasma and urine enrichments following infusion of L-[1-13C]phenylalanine and L
      [ring-2H5]phenylalanine in humans: evidence for an isotope effect in renal
      tubular reabsorption.
AB  - Amino acids labeled with 13C or deuterium are commonly used in studies of amino
      acid metabolism. Traditionally, amino acid flux has been estimated by measurement
      of isotopic enrichment in the plasma pool; however, urine sampling as a
      noninvasive means of determining isotope enrichment has been increasing. The
      isotope enrichments and fluxes estimated from plasma and urine sampling were
      compared when two phenylalanine tracers (L-[1-13C]phenylalanine and L-[ring
      2H5]phenylalanine) were intravenously infused for 4 hours in seven healthy men.
      This is the first evaluation of these isotopes as urinary tracers for assessing
      amino acid metabolism in adult humans. Before infusion, the mean ratio of plasma
      to urine (P:U) isotope enrichment was 0.99 +/- 0.03 (SD) and 0.99 +/- 0.02 for
      [13C]phenylalanine and [13C]tyrosine, respectively (isotope enrichment of
      [2H5]phenylalanine is zero at baseline). At isotopic steady state, the ratio was
      1.06 +/- 0.05, 0.98 +/- 0.03, and 0.60 +/- 0.10 for [13C]phenylalanine,
      [13C]tyrosine, and [2H5]phenylalanine, respectively. The [13C]phenylalanine
      isotope showed a high correlation (R2 = .96) between enrichment in plasma and
      urine. However, use of [2H5]phenylalanine resulted in a significantly higher
      enrichment in urine than in plasma. Since amino acid flux is inversely related to
      enrichment, urine sampling would result in an underestimation of flux. The plasma
      to urine difference is probably due to discrimination of the [2H5]phenylalanine
      isotope in renal transport; therefore, this isotope may not be suitable for in
      vivo use where cellular transport mechanisms are involved.

PMID- 8159110
TI  - Effects of combined insulin and sorbinil treatment on diabetes-induced vascular
      dysfunction in rats.
AB  - These experiments were undertaken to assess the effects of combined treatment
      with insulin (designed to partially restore metabolic control) and sorbinil (an
      aldose reductase inhibitor [ARI]) versus the effects of sorbinil alone or of two
      insulin regimens providing different degrees of glycemic control on diabetes
      induced metabolic derangements and vascular function. Streptozocin-diabetic rats
      were divided into the following five groups: (1) untreated (D); (2) treated with
      approximately 1 U NPH insulin/100 g body weight/d administered in one
      subcutaneous (SC) injection (DI-1); (3) treated with the same total daily dose of
      insulin administered in two SC injections (DI-2); (4) treated with approximately
      0.2 mmol sorbinil in the diet/kg body weight/d (DS); and (5) treated with once
      daily insulin plus sorbinil (DSI-1). Two groups of nondiabetic rats, untreated
      (C) and sorbinil-treated (CS), served as controls. Metabolic parameters were
      unaffected by sorbinil treatment in controls and diabetics, whereas insulin
      administration in the diabetics virtually normalized body growth, food
      consumption, urine volume, and plasma glucose levels, and markedly decreased
      hemoglobin A1 (HbA1) levels. Two daily injections were more effective than one in
      improving metabolic control as measured by HbA1 levels. Regional vascular 131I
      albumin permeation was increased about twofold to threefold by diabetes in ocular
      tissues, sciatic nerve, aorta, diaphragm, and new granulation tissue; it was
      decreased (but not normalized) by insulin treatment in accordance with improved
      metabolic control, and was completely normalized by sorbinil. 131I-albumin kidney
      clearance, as well as urinary albumin and IgG excretion, were markedly increased
      in diabetic rats and were significantly decreased but not completely normalized
      by sorbinil and by twice-daily insulin treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8159111
TI  - Determinants of insulin sensitivity and consequences for lipoproteins and blood
      pressure in subjects with non-insulin-dependent diabetes mellitus.
AB  - The aim of the present study was to investigate the possible determinants of
      insulin sensitivity and the relationships of these determinants and insulin
      sensitivity to lipoprotein levels and blood pressure in patients with non-insulin
      dependent diabetes mellitus (NIDDM). We studied 46 patients with NIDDM (26 women,
      20 men) treated either with diet alone or in combination with sulfonylureas.
      Insulin sensitivity was assessed as the insulin-mediated glucose uptake rate (M
      value) with the hyperinsulinemic euglycemic clamp technique. In a multiple
      regression model, only percent body fat, waist to hip ratio (WHR), and resting
      energy expenditure (REE) emerged as significant independent determinants of the M
      value, with a multiple R2 for the model of 44%, whereas age, hemoglobin A1c
      (HbA1c) level, thyroid function, fitness level, smoking status, alcohol
      consumption, and dietary habits did not contribute significantly. The M value was
      independently and negatively associated with the concentrations of triglyceride
      (TG) and very-low-density lipoprotein (VLDL) cholesterol and positively
      associated with high-density lipoprotein (HDL) cholesterol subfractions and
      apolipoprotein A1. In our predominantly normotensive subjects, we found no
      association between the M value and blood pressure. Moreover, fasting insulin
      contributed directly, ie, independent of the M value, to the variation of TG, but
      not to the other lipoproteins and not to blood pressure. The results suggest that
      in NIDDM (1) insulin sensitivity is determined mainly by percentage body fat and
      REE, (2) the insulin level determines the TG level directly, whereas the
      lipoproteins are influenced indirectly as a reflection of the degree of insulin
      resistance, and (3) insulin sensitivity is not related to blood pressure in a
      normotensive population.

PMID- 8159112
TI  - The relationship of epinephrine excretion to serum lipid levels: the Normative
      Aging Study.
AB  - Catecholamines are known to stimulate lipolysis of triglyceride stores in adipose
      tissue. However, the relationship of sympathoadrenal activity to serum lipid and
      lipoprotein concentrations remains uncertain. Since obesity, particularly the
      centripetal form, has recently been shown to be associated with increased urinary
      excretion of norepinephrine and decreased excretion of epinephrine, the
      possibility that the sympathoadrenal system is involved in the lipid
      abnormalities associated with the centripetal form of obesity was investigated.
      The relationship between 24-hour urinary catecholamine excretion and serum lipid
      and lipoprotein levels was examined among 615 male participants of the Normative
      Aging Study. Epinephrine excretion was positively correlated with the high
      density lipoprotein cholesterol (HDL-C) level and the ratio of HDL-C to low
      density lipoprotein cholesterol ([LDL-C] r = .15, P = .0002, and r = .11, P =
      .007, respectively) and inversely correlated with the triglyceride level (r = 
      .14, P = .0005). These relationships remained significant after adjusting for the
      effects of age, smoking, alcohol intake, adiposity, and insulin level.
      Epinephrine excretion was not significantly related to levels of total
      cholesterol or LDL-C. Norepinephrine and dopamine excretion were not
      significantly related to any lipid variable. These data suggest that (1)
      epinephrine plays an important role in regulating lipid and lipoprotein
      metabolism in humans, and (2) decreased adrenal medullary activity may contribute
      to the dyslipidemia (increased triglycerides and decreased HDL-C) commonly
      observed among the obese. The sympathoadrenal system therefore, along with
      hyperinsulinemia, may contribute to the increased cardiovascular risk associated
      with the insulin resistance syndrome.

PMID- 8159113
TI  - Influence of thyroid status on the paradoxical growth hormone response to
      thyrotropin-releasing hormone in human obesity.
AB  - Thyrotropin-releasing hormone (TRH) tests were performed in 38 age- and weight
      matched obese but otherwise healthy men. In all subjects, total thyroxine (T4)
      and triiodothyronine (T3) concentrations were in the normal range. According to
      basal and TRH-stimulated serum thyrotropin (TSH) levels, subjects were divided
      into the following three groups: group I (n = 14), euthyroid subjects; group II
      (n = 11), euthyroid subjects with normal basal but abnormally elevated TSH
      responses to TRH; group III (n = 13), subjects with elevated basal and TRH
      induced TSH levels (subclinical hypothyroidism). Basal TSH levels were 1.8 +/-
      0.4 mU/L in group I, 1.7 +/- 0.3 in group II, and 6.0 +/- 0.7 in group III. In
      both groups II and III, TRH-induced TSH increments were above the normal range
      (maximal increment > 14 mU/L) and were significantly higher than in group I. The
      definition of euthyroidism for groups I and II and of subclinical hypothyroidism
      for group III according to the basal levels of TSH was confirmed by clinical
      (Billewicz index), hormonal (serum free-T4 levels), and metabolic (serum
      apoprotein [apo] AI levels) parameters. Basal concentrations of growth hormone
      (GH) were similar in all groups. When GH levels after TRH stimulation were
      measured, significant increments (peak minus baseline > 5 micrograms/L) were
      observed in nine of 13 hypothyroid obese men. The overall mean peak GH increase
      in group III was 4.5 times higher than baseline and was observed at 45 minutes.
      None of the euthyroid obese subjects of groups I and II showed any significant
      change in GH levels in response to TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159114
TI  - The effects of sodium bicarbonate and a mixture of sodium bicarbonate and
      carbonate ("Carbicarb") on skeletal muscle pH and hemodynamic status in rats with
      hypovolemic shock.
AB  - Rats rendered hypotensive and acidotic by withdrawal of blood were treated by
      infusion of either an equimolar mixture of sodium bicarbonate and sodium
      carbonate ("Carbicarb"), sodium bicarbonate alone, or sodium chloride. Skeletal
      muscle intracellular pH (pHi) was measured using magnetic resonance spectroscopy
      from the chemical shift of the carbon-2 (C2) proton resonance of the imidazole
      ring of anserine. In the groups treated with alkali, arterial blood pH (pHa) was
      restored to normal, but no change was observed in the sodium chloride-treated
      animals. Despite an elevation of arterial blood partial pressure of CO2 (PaCO2)
      in the group treated with sodium bicarbonate, no significant change in pHi was
      observed in any group. Blood lactate levels, initially elevated in all groups,
      underwent only minor changes. In all three groups a transient and similar
      elevation of arterial blood pressure was observed after infusion. Differential
      effects of Carbicarb and sodium bicarbonate in metabolic acidosis may be
      dependent on the model of metabolic acidosis used, and an alteration in PaCO2
      induced by alkali therapy may not be a major determinant of changes in pHi.

PMID- 8159115
TI  - Is there a sex difference in the association of plasma insulin level and insulin
      sensitivity with serum lipids and lipoproteins?
AB  - Previous studies on the relationship between the plasma insulin level, insulin
      sensitivity (SI), serum lipids, and lipoproteins have been performed
      predominantly in men. Therefore, we investigated whether there is a sex
      difference in the association of insulin level during an oral glucose tolerance
      test and SI with lipids and lipoproteins among normoglycemic men and women aged
      53 to 61 years. SI was determined by the minimal model from the frequently
      sampled intravenous glucose tolerance test (IVGTT). There were no correlations
      between total cholesterol or low-density lipoprotein (LDL) cholesterol and
      insulin level or SI. High-density lipoprotein (HDL) cholesterol correlated
      inversely with fasting insulin (r = -.26, P < .05 in men; r = -.29, P < .01 in
      women) and 2-hour insulin (r = -.31, P < .01 in men; r = -.39, P < .001 in women)
      and positively with SI (r = .28, P = .05 in men; r = .43, P < .001 in women).
      Total and very-low-density lipoprotein (VLDL) triglycerides correlated positively
      with fasting insulin (r = .43, P < .001 in men; r = .42, P < .001 in women) and 2
      hour insulin (r = .50, P < .001 in men; r = .31, P < .01 in women) and inversely
      with (r = -.49, P < .001 in men; r = -.40, P < .001 in women). In multiple
      regression analyses including age, body mass index (BMI), waist to hip ratio, 2
      hour glucose, fasting or 2-hour insulin, and SI, only BMI was associated with HDL
      cholesterol level in men.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159116
TI  - Insulin sensitivity, insulin secretion, and glucose effectiveness in anorexia
      nervosa: a minimal model analysis.

PMID- 8159117
TI  - The family.

PMID- 8159118
TI  - Bridging the gap between research and practice: an assessment of the value of a
      study day in developing critical research reading skills in midwives.
AB  - Despite increasing professional pressure on midwives to make their clinical
      practice research based, their remains a considerable amount of clinical activity
      which relies only on historical ritual rather than on rational scientific
      evidence. This apparent failure to integrate research into practice has generated
      a lot of debate regarding its cause. One widely accepted reason for midwives' non
      use of empirical findings is simply that a large proportion of the workforce does
      not have the knowledge and training in the necessary skills to enable them to
      assess the value of published articles. Clearly the cost in time and human
      resources involved in providing a thorough training for the entire midwifery
      workforce in research skills would probably be unnecessary for the majority of
      midwives who simply want to be able to translate published research into their
      clinical practice. Consequently, a more pragmatic approach might be to assess the
      value of brief training days in developing midwives' competencies in reading
      research articles critically as a precursor to facilitating the integration of
      theory and practice. If the value of such courses could be demonstrated, then it
      is conceivable that study days of this type might be made more widely available
      for all midwifery personnel. This study investigated the effectiveness of one
      such study day in (a) modifying the participating midwives' evaluations of a
      published research article in accord with those of expert judges and (b)
      influencing the longer term use by the participants of published research. The
      day provided a brief introduction to basic research techniques both in theory and
      in practice, as well as a set of structured guidelines for evaluating research
      articles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159119
TI  - The experience of childbirth for survivors of incest.
AB  - The purpose of this research was to discover what experiences, including
      feelings, women who are survivors of incest have during childbirth. The
      recognition that the childbirth experience may trigger memories of incest that
      will then alter the course of childbirth was the framework for the study. This
      exploratory research was undertaken using a phenomenological approach. The six
      participants were obtained through networking and issues surrounding
      confidentiality and consent were of a high priority. The data consists of
      transcripts of taped, one to two hour, in-depth interviews. During interviews
      each woman recalled her experiences and feelings during and surrounding
      childbirth. Qualitative analysis was undertaken, the findings indicating that
      memories of previous abuse may be provoked by childbirth but that it is a very
      individualised response. The effect of these memories on the childbirth
      experience is also variable but does occur. Privacy, control and touch are
      important aspects of these women's childbirth experiences. The results and
      interpretation of findings presented in this report centre around the labour and
      delivery experiences of the women. The variety of women's needs demonstrated in
      this project emphasise the importance of individualised care by midwives and
      doctors involved in the care of childbearing women.

PMID- 8159120
TI  - The International Year of the Family.
AB  - 1994 is the International Year of the Family. In this paper the background to the
      instigation of the Year, its raison d'etre and how it is hoped this will be
      achieved are described. Whether the family will be any better off because of the
      Year can only be judged in the future but at least this Year will have brought
      the family to the forefront of international discussion and debate.

PMID- 8159121
TI  - Postnatal home visiting by midwives.
AB  - Information about postnatal home visiting is presented from a postal survey of
      all directors of midwifery in English NHS districts, carried out in April and May
      1991. The main finding was that almost all districts had changed from the
      traditional policy of daily home visits up to the tenth postnatal day to
      selective home visits by midwives. What was meant by 'selective' varied greatly,
      however, and the study highlighted the need to carry out audits of postnatal
      midwifery visiting.

PMID- 8159122
TI  - Who chooses to have the HIV antibody test in the antenatal clinic?
AB  - With the increase in human immunodeficiency virus (HIV) seroprevalence amongst
      antenatal clinic attenders, and given that current medical opinion considers it
      desirable that a woman is aware of her serostatus, it has been recommended that
      the HIV test is offered to all women in the antenatal clinic and that its uptake
      is monitored. This paper reports on the uptake rate during the 12 months to
      February 1990 at a central London hospital, which was 17%, and the
      characteristics of the women who agreed to be tested for HIV. Using information
      collected by the midwife on an interactive computer during the 'booking'
      interview, it was found that women who were single and not in a stable
      relationship (p < 0.001) and those who described themselves as Mediterranean (p <
      0.01) were more likely to accept the test. Caucasian women (p < 0.05) and married
      women (p < 0.05) were less likely to accept the test. Accepters did not differ
      from decliners in any other variable examined. Possible reasons for these
      differences are discussed.

PMID- 8159123
TI  - No effect of birth centre care on either duration or experience of breast
      feeding, but more complications: findings from a randomised controlled trial.
AB  - OBJECTIVE: to study the effect of birth centre care on the duration of breast
      feeding, breast feeding complications, and women's experiences of breast feeding.
      DESIGN: randomised controlled trial. SETTING: in-hospital birth centre at South
      Hospital, Stockholm, and standard obstetric care in the Greater Stockholm area.
      SUBJECTS: 1230 women with expected date of birth between October 1989 and
      February 1992, interested in participating in a birth centre trial, and meeting
      medical low-risk criteria. 617 women were allocated to the experimental group
      offered birth centre care (EG), and 613 to the control group offered standard
      obstetric care (CG). MAIN OUTCOME MEASURES: duration of breast feeding, breast
      feeding complications such as sore nipples, engorgement, milk stasis, and
      mastitis, and women's experiences of breast feeding. FINDINGS: no difference was
      found between EG and CG in the duration of breast feeding. Ninety-three per cent
      in both groups were breast feeding exclusively two months post partum. The
      average number of months of breast feeding, exclusively or partly, when
      investigated one year after the birth was 8.6 in EG and 8.5 in CG. No difference
      was observed in women's experiences of breast feeding, but rather more women in
      EG than in CG reported sore nipples, 36% and 30% respectively (p = 0.03), and
      milk stasis, 26% and 19% respectively (p = 0.002). CONCLUSIONS: birth centre care
      had no effect on the duration of breast feeding, or on women's experiences of
      breast feeding. Prenatal attitudes were probably more significant predictors of
      these outcomes than differences in the two modes of maternity care in this
      population of highly breast feeding-motivated women. The larger proportion of
      sore nipples and milk stasis in the EG might have been due to earlier discharge,
      or to midwives less skilled in assisting with breast feeding at the birth centre
      than in the postpartum wards.

PMID- 8159124
TI  - A comparison of whole cell protein profiles for sporadic human isolates of
      Streptococcus equisimilis and beta-haemolytic group G streptococci.
AB  - Whole cell protein profiles were resolved for Streptococcus equisimilis (group C)
      and large colony human biotype beta-haemolytic group G streptococci by the use of
      one dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
      Strains of S. equisimilis (27 in toto) were distributed among eight patterns
      designated A to H. Pattern A represented 48.2% of the latter isolates. Strains of
      group G streptococci (59 in toto) were distributed among sixteen patterns
      designated 1-16, and there were no predominant patterns which represented more
      than 20% of all strains. Profiles were reproducible, not susceptible to strain
      passage, but susceptible to variation in growth media. Considerable homology was
      observed among bacteria in either Lancefield group.

PMID- 8159125
TI  - Monitoring of selected bacteria and fungi in sand and sea water along the Tel
      Aviv coast.
AB  - Monitoring sand and sea water of the Mediterranean Tel Aviv beaches during 1989
      1991 for bacterial quality showed varying data and no correlation between
      standard bacteria parameters (SBP) and potential pathogenic bacteria (PPB). An
      exceptional feature was observed in 1989 when faecal coliforms including
      Escherichia coli and faecal Streptococcus were less in sand than in sea water.
      These results may be attributed to the low turbulent activity of the sea in 1989,
      particularly in summer, compared with the next two years. In 1990 the number of
      SBP and PPB was always higher in sand than in sea water. The most frequent micro
      organisms isolated from sand were E. coli, Pseudomonas aeruginosa and Candida
      albicans. Intensive engineering work and the construction of a chlorinator for
      sewage probably caused a dramatic drop in the number of SBP and PPB in sea water
      and sand during 1990-1991 on some beaches. Campylobacter jejuni was isolated from
      sand, and may be considered a possible hazard factor for enteritis in the
      population bathing at these beaches.

PMID- 8159126
TI  - Adherence pattern of non-pilated Aeromonas hydrophila strains to tissue cultures.
AB  - Adherence of non-pilated Aeromonas hydrophila strains to HEp-2, HeLa, CHO and
      Vero tissue culture cells was studied. The strains were isolated from intestinal
      and extra-intestinal human infections and from the environment. The environmental
      isolates revealed a diffuse type of adherence to all types of cell lines while
      clinical isolates showed localized adherence (50%). Strains revealing the diffuse
      type of adherence showed high levels of adhesion i.e. > 20 bacteria per cell.
      This activity correlated with hydrophobicity of the strains tested.
      Haemagglutination assay with human erythrocytes was negative, showing no
      association with plasmid profile, Congo red binding and adherence to tissue
      culture cells. Thus the experiments showed that in non-pilated strains,
      hydrophobicity may be the major factor responsible for adherence to epithelial
      cells.

PMID- 8159127
TI  - Lysis of cyanobacteria with Flexibacter spp isolated from domestic sewage.
AB  - Five species of filamentous cyanobacteria and two species of Flexibacter were
      isolated from domestic sewage. Cells and filtrates of F. flexilis and F. sancti
      lysed the cyanobacterium Oscillatoria williamsii. Inhibition of the
      photosynthetic electron transport reactions, and glycolate dehydrogenase and
      nitrogenase activity of O. williamsii due to its incubation with F. flexilis,
      were observed. Scanning electron micrographs revealed the attachment of F.
      flexilis to the sheaths of O. williamsii which resulted in the excretion of
      lysozyme and lysis of the cyanobacterium. Seasonal variations of Flexibacter spp
      showed that they were more abundant in the aeration tanks during June compared
      with sewage effluents.

PMID- 8159129
TI  - Mobile epidural infusions after awake caesarean birth.

PMID- 8159128
TI  - Antimicrobial activity of natural and semisynthetic diterpenoids from Sideritis
      spp.
AB  - The antimicrobial activity of 22 natural diterpenoids of endemic Sideritis from
      Eastern Andalusia (Spain) is described. Only ent-kaur-16-ene foliol and ent-beyer
      15-ene isopusillatriol proved to be active towards Gram-positive and acid-fast
      bacteria. The introduction of a ketonic group at C-15 on ent-kaur-16-enic systems
      produced a remarkable degree of activity.

PMID- 8159131
TI  - Smoking and pregnancy survey. Health Education Authority.

PMID- 8159130
TI  - The obstetric anaesthetist and the sick obstetric patient--with special reference
      to fulminating pre-eclamptic toxaemia.

PMID- 8159132
TI  - Care study: severe needle phobia.

PMID- 8159133
TI  - Gabapentin--a new anticonvulsant.

PMID- 8159134
TI  - Nutrition support in organ failure.

PMID- 8159135
TI  - Nutrition care of patients with acute and chronic respiratory failure.
AB  - Nutrition is intimately linked to pulmonary function and an understanding of
      these relationships have therapeutic utility. Malnutrition is known to be
      associated with impaired mechanical function of the lung in both chronic and
      acute respiratory insufficiency. Refeeding results in improvement in functional
      characteristics and may be critical in the weaning of patients from mechanical
      ventilation. In contrast, overfeeding may result in an increased ventilatory
      demand resulting in the inability to wean from respiratory support. This article
      considers the background as well as recommendations for the nutritional care of
      patients with acute and chronic respiratory failure.

PMID- 8159136
TI  - A case of retrograde jejunoduodenal intussusception caused by a feeding
      gastrostomy tube.
AB  - A case is presented of migration of a gastrostomy feeding tube (Foley type)
      through the pylorus with duodenal obstruction and subsequent retrograde
      intussusception. Although feeding tube migration is not uncommon, retrograde
      intussusception of the jejunum into the duodenum is rare. In this case, surgery
      was required with resection of a segment of necrotic bowel. Recommendations are
      given for treatment of this unusual complication with emphasis on its avoidance
      through use of a retaining bar or disc at the tube's skin exit site.

PMID- 8159137
TI  - Nutrition considerations in the neonatal extracorporeal life support patient.
AB  - Extracorporeal life support (ECLS) is a type of heart-lung bypass commonly used
      to support neonates with life-threatening respiratory or cardiac failure. These
      patients are among the most critically ill patients in the neonatal intensive
      care unit and are at significant nutritional risk. Unfortunately, there is a
      paucity of literature regarding guidelines for nutrition support of the neonatal
      ECLS patient. The purpose of this article is to provide an overview of the
      indications, techniques, and complications of ECLS and to address the approach to
      nutrition support of these patients. Emphasis will be placed on issues unique to
      the neonatal ECLS patient.

PMID- 8159138
TI  - Nutrition support in specific diseases: back to basics.
AB  - The nutrition care of a patient is complicated by the recent proliferation of
      commercially available specialty products. Rational and objective guidelines are
      necessary to direct formula selection for use in specific diseases. Consideration
      of the patient's nutritional status, functioning of major organ systems, and
      alterations in nutrient metabolism are essential. The diagnosis of a specific
      disease does not necessitate the use of a specialty product in all instances.
      Many times modification of a standard formula can result in safe and effective
      nutrition. Basic nutrition principles should continue to guide the clinician as
      the definitive answers to the issues surrounding metabolic support in patients
      with specific disease states become available.

PMID- 8159139
TI  - Nutrition and the kidney: how to manage patients with renal failure.
AB  - Nutrition is believed to play a key role in the management of chronic and acute
      renal failure. Considerable evidence suggests that unrestricted protein diets
      accelerate the progression of chronic renal failure. As a result, recommendations
      have evolved limiting the quantity and quality of nitrogen intake with the goal
      of slowing the progression to dialysis dependency. Acute renal failure offers
      different challenges in view of its common association with hypermetabolic
      states. With respect to nitrogen substrate administration, the use of mixed
      formulations of essential plus nonessential amino acids seems to be as effective
      as essential amino acids alone.

PMID- 8159140
TI  - The means of concentrating (making more "energy dense") parenteral nutrition
      solutions.

PMID- 8159141
TI  - Severe hypophosphatemia in postoperative patients.

PMID- 8159142
TI  - "Use of indirect calorimetry in clinical nutrition".

PMID- 8159143
TI  - Striking the balance--a nurse teacher's dilemma.

PMID- 8159144
TI  - Project 2000 student wastage: a case study.
AB  - High wastage rates associated with the nursing profession were a contributory
      factor driving recent reforms in the form of Project 2000 (P2000). Such changes
      beg the question: to what extent has this new educational initiative affected
      current wastage patterns among nursing students? This paper examines whether or
      not this new initiative is having an effect on student wastage at a first-wave
      college of nursing, midwifery and health visiting which implemented P2000 in
      1989. Thus far, 10 cohorts of students have been admitted on to the course, seven
      full-time and three part-time. It is hoped other institutions involved in nurse
      education and training may gain some beneficial insights from the lessons learnt
      and measures taken to stem wastage at the college described in this case study.

PMID- 8159145
TI  - Mentorship in nursing and midwifery education: issues for research.
AB  - Despite an apparent concensus that mentorship is an important aspect of learning
      in the practice continuum, there has been no real critical appraisal of the
      literature for its research base. References to published work on mentorship may
      merely uncritically repeat non-researched statements which, in turn, may not
      always be relevant to nursing and midwifery education in the UK. This paper sets
      out to begin to construct a research agenda for mentorship, free of statutory and
      regulatory constraints about meaning and practice.

PMID- 8159146
TI  - Might history repeat itself?
AB  - Having recently moved into medical education, after spending many years in
      teacher education, the writer is struck by some parallels between the positions
      in which health and education now find themselves: subject to fundamental reform
      premised upon the creation of a social market and an extension to consumer
      choice, while discounting professional judgment. The paper analyses the
      implementation of teacher education reforms in the 1970s and 1980s, against a
      background of economic constraint. It then considers the recent reversal of those
      changes, as part of a wider reappraisal of social policy, heavily influenced by
      ideologies associated with the 'new right', which have underpinned reforms
      designed, in part, to curtail the traditional independence of professional groups
      and, in the name of greater accountability to consumers, substitute greater
      central control. Pre- and Post-Registration Education for health care
      professionals, now finds itself in a similar position to that which was evident
      in teacher education, when the writer joined. Since education and health both
      constitute major areas of social policy, the paper speculates whether the latter
      will, in the future, follow the same path as that described in relation to the
      former. In particular the control of the education of health care professionals
      is seen to be central to their ability to continue to offer reasoned critiques of
      political initiatives.

PMID- 8159147
TI  - One step along the way: the introduction of supernumerary status for RGN students
      in Foresterhill College, Aberdeen.
AB  - This article describes the introduction of supernumerary status for RGN students.
      A revised modular scheme was implemented and the main aims were to introduce
      supernumerary status and to provide the students with an identified 'mentor'. The
      changes were evaluated from teacher, student and ward staff perspectives.
      Supernumerary status was introduced successfully but mentorship less so. Finally,
      the significant change is reflected upon in light of current and future changes
      in nurse education.

PMID- 8159148
TI  - The views of students and teachers on the use of portfolios as a learning and
      assessment tool in midwifery education.
AB  - As the introduction of devolved continuous assessment in midwifery education has
      led to the introduction of new and varied learning and assessment strategies,
      there is a need to evaluate their use. The focus of this study is on the views of
      students and teachers and on portfolios as a learning and assessment tool in
      midwifery education. In a small exploratory study questionnaires were used to
      obtain both quantitative and qualitative data from 24 student midwives. Eight
      tutors were also interviewed. Data was analysed using an adapted version of
      grounded theory. Many students had negative feelings about the use of portfolios.
      In particular problems related to lack of motivation, uncertainty about what was
      expected of them, difficulty in expressing personal thoughts and feelings and the
      subsequent anxiety that this created. Tutors showed some awareness of the
      relative merits associated with the use of portfolios for learning and
      assessment. Although some of the students problems in keeping the portfolio were
      appreciated by the tutors, the students perceived there were few attempts made to
      rectify or minimise these difficulties.

PMID- 8159149
TI  - Evaluation of a community staff preparation strategy for the teaching, assessing
      and mentorship of Project 2000 diploma students.
AB  - This article presents findings of a study which investigated effectiveness of an
      educational strategy for community nurses in relationship to their teaching,
      assessing and mentorship roles with Project 2000 diploma student nurses. The
      research was conducted in the North Staffordshire Health District when the
      College of Nursing and Midwifery's first cohort of Project 2000 diploma students
      were in their third year of studies. Data were collected using a postal
      questionnaire and face-to-face interviews. The findings reveal that just over
      half the sample felt they had adequate preparation for their role of teachers and
      assessors of Project 2000 diploma students. Analysis of the data showed that
      there had been a need initially for more information to be disseminated regarding
      the college curriculum and assessment criteria. Chi square analysis revealed a
      significant result in relationship to those in the sample who felt they were
      adequately prepared for their teaching and assessment role and those who had
      undertaken a formal teaching and assessing course. The findings have implications
      for the desirability of community nurses to undertake formal teaching and
      assessing courses. Conclusions can also be drawn regarding future ventures in
      curriculum innovation and the need for adequate clinical staff preparation for
      changed needs of a curriculum.

PMID- 8159150
TI  - The management of individual performance planning and review: some limitations on
      rationality.
AB  - Individual performance planning and review has a long and turbulent history.
      Colleges of nursing and higher education are incorporating performance review
      schemes as a part of their quality management systems, BS 5750 and the like. This
      in the rational belief that chances of success will be enhanced. The reliability
      and validity of performance review schemes is explored, in particular the belief
      that rational planning underpins success. The value of results oriented
      performance review with its emphasis upon dialogue is seen to be of value for
      organisational learning and the de-reification of nurse education institutes as
      somewhat rigid systems. The incorporation of qualitative action research methods
      within a results oriented frame may herald a significant leap forward in the
      quality assurance of nurse teaching.

PMID- 8159151
TI  - Preceptorship and post-registration nurse education.
AB  - The Report of the Post-Registration Education and Practice Project (UKCC 1990)
      and the Framework for Continuing Professional Education for Nurses, Midwives and
      Health Visitors (ENB 1991) have led to an unprecedented period of formalised
      supervision and support for registered practitioners in the UK. The preceptor has
      been identified as having a pivotal part to play in providing this support. There
      is however, a need for further clarification regarding the exact nature of the
      preceptor's role in post-registration education and practice, and the full extent
      of the responsibilities involved. This paper explores the issues involved in
      preceptorship for qualified nurses and some of the related literature. The
      following key questions are addressed: Who will be designated as preceptors? How
      will they be selected? What preparation and support will such preceptors be
      offered? What is the role of the preceptor and what is the conceptual and
      empirical difference between the preceptor and the mentor? It is proposed that
      strategies must be identified for clarification of the preceptor's role and
      responsibilities, identification of selection criteria, and the establishment of
      preceptor preparation programmes and support networks.

PMID- 8159152
TI  - The telephone interview as a data collection method.
AB  - The interview is one of the most frequently used methods of collecting
      qualitative data. This paper offers a description of how the telephone interview
      may be used to collect data in both qualitative and quantitative studies. It
      offers a description of how to plan and use the telephone as a means of
      collecting data and justifies the use of this method. The paper also describes
      and illustrates how textual data that arises from the use of telephone interviews
      may be analysed by computer. Two approaches to analysis are outlined: (1) simple
      drawing together of responses to questions and (2) the searching for categories
      within the data and the organisation of text within those categories. The paper
      identifies limitations of the approach to data collection and points to further
      reading on the topic.

PMID- 8159153
TI  - Zidovudine for the prevention of HIV transmission from mother to infant.
AB  - Worldwide, perinatal (i.e., mother to infant) transmission accounts for most
      human immunodeficiency virus (HIV) infections among children; in the United
      States, of the approximately 7000 infants born to HIV-infected mothers each year,
      1000-2000 are HIV-infected. Strategies for reducing perinatally acquired HIV
      infection have included preventing HIV infection among women and, for HIV
      infected women, avoiding pregnancy or refraining from breastfeeding their
      infants. On February 21, 1994, the National Institutes of Health's National
      Institute of Allergy and Infectious Diseases (NIAID) and National Institute of
      Child Health and Human Development (NICHD) announced preliminary results from a
      randomized, multicenter, double-blinded clinical trial of zidovudine (ZDV) to
      prevent HIV transmission from mothers to their infants (AIDS Clinical Trials
      Group [ACTG] protocol 076). This report summarizes the interim results of that
      trial, which indicate effectiveness of ZDV for prevention of perinatal
      transmission.

PMID- 8159154
TI  - Differences in infant mortality between blacks and whites--United States, 1980
      1991.
AB  - National health objectives for the year 2000 include reducing the overall infant
      mortality rate (i.e., deaths at age < 1 year per 1000 live births) to no more
      than 7.0 per 1000 live births (objective 14.1) and the infant mortality rate for
      blacks to no more than 11.0 (objective 14.1a). Achieving this goal will require
      reducing the race-specific differences in infant mortality. During 1979-1981,
      infant mortality was the second leading cause of excess deaths among blacks aged
      < 45 years, accounting for approximately 6000 more deaths among black infants
      than among white infants. Since 1960, rates for infant mortality and low
      birthweight (LBW) (< 2500 g [< 5 lbs, 8 oz]) for blacks were twice those for
      whites; these ratios remained stable through the early 1980s. To characterize
      current trends in the ratios of race-specific infant mortality, LBW, and very low
      birthweight (VLBW) (< 1500 g [< 3 lbs, 4 oz]) rates among blacks and whites, data
      were analyzed from published reports of final birth and mortality statistics from
      1980 through 1991*. This report summarizes the results of that analysis.

PMID- 8159155
TI  - Populations at risk from particulate air pollution--United States, 1992.
AB  - Despite improvements in air quality since the 1970s, air pollution remains an
      important environmental risk to human health. A national health objective for the
      year 2000 is to reduce exposure to air pollutants so that at least 85% of persons
      live in counties that meet U.S. Environmental Protection Agency (EPA) standards
      (objective 11.5). This report provides estimates from the American Lung
      Association (ALA) of populations potentially at risk from exposure to particulate
      air pollution in the United States during 1992.

PMID- 8159156
TI  - Update: dracunculiasis eradication--Ghana and Nigeria, 1993.
AB  - In 1989, Ghana and Nigeria, countries in west Africa, ranked first and second in
      the number of reported cases of dracunculiasis (i.e., Guinea worm disease) with
      179,556 cases and 640,008 cases respectively. During 1987-1988, Global 2000 and
      the World Health Organization (WHO) Collaborating Center for Research, Training,
      and Eradication of Dracunculiasis at CDC initiated direct, on-site assistance for
      the eradication of dracunculiasis in Ghana and Nigeria. This report summarizes
      surveillance data for the two countries during 1993 and describes efforts toward
      eradication of dracunculiasis.

PMID- 8159157
TI  - Prevalence of arthritis--Arizona, Missouri, and Ohio, 1991-1992.
AB  - Although regional and national data about arthritis can be used to develop
      synthetically derived measures of prevalence for states (1), few state surveys
      exist for determining the prevalence and impact of arthritis at that level. To
      measure state-specific prevalences, during 1991-1992 Arizona, Missouri, and Ohio
      added questions about arthritis to their Behavioral Risk Factor Surveillance
      System (BRFSS) surveys. This report presents BRFSS-derived estimates of self
      reported prevalence of clinically diagnosed arthritis in these states and
      characteristics of adults who reported this disorder.

PMID- 8159158
TI  - Tetanus--Kansas, 1993.
AB  - In 1993, two tetanus cases were reported to the Kansas Department of Health and
      Environment--the first cases reported in the state since 1987. This report
      summarizes the findings of the case investigations.

PMID- 8159160
TI  - International decade for natural disaster reduction.

PMID- 8159159
TI  - Maternal hepatitis B screening practices--California, Connecticut, Kansas, and
      United States, 1992-1993.
AB  - Each year in the United States, an estimated 22,000 infants are born to women
      with chronic hepatitis B virus (HBV) infection. These infants are at high risk
      for perinatal HBV infection and chronic liver disease as adults. The American
      College of Obstetrics and Gynecology, the American Academy of Pediatrics, the
      American Academy of Family Practice, and the Advisory Committee on Immunization
      Practices each have recommended that all pregnant women be routinely tested for
      hepatitis B surface antigen (HBsAg) during an early prenatal visit in each
      pregnancy to identify newborns who require immunoprophylaxis for the prevention
      of perinatal HBV infection (1-4). To evaluate progress in implementing this
      recommendation, surveys were conducted to assess the effectiveness of maternal
      HBsAg screening in three states--California, Connecticut, and Kansas--and a
      sample of hospitals in the United States.

PMID- 8159161
TI  - Cloning of the blasticidin S deaminase gene (BSD) from Aspergillus terreus and
      its use as a selectable marker for Schizosaccharomyces pombe and Pyricularia
      oryzae.
AB  - Aspergillus terreus produces a unique enzyme, blasticidin S deaminase, which
      catalyzes the deamination of blasticidin S (BS), and in consequence confers high
      resistance to the antibiotic. A cDNA clone derived from the structural gene for
      BS deaminase (BSD) was isolated by transforming Escherichia coli with an
      Aspergillus cDNA expression library and directly selecting for the ability to
      grow in the presence of the antibiotic. The complete nucleotide sequence of BSD
      was determined and proved to contain an open reading frame of 393 bp, encoding a
      polypeptide of 130 amino acids. Comparison of its nucleotide sequence with that
      of bsr, the BS deaminase gene isolated from Bacillus cereus, indicated no
      homology and a large difference in codon usage. The activity of BSD expressed in
      E. coli was easily quantified by an assay based on spectrophotometric recording.
      The BSD gene was placed in a shuttle vector for Schizosaccharomyces pombe,
      downstream of the SV40 early region promoter, and this allowed direct selection
      with BS at high frequency, following transformation into the yeast. The BSD gene
      was also employed as a selectable marker for Pyricularia oryzae, which could not
      be transformed to BS resistance by bsr. These result promise that the BSD gene
      will be useful as a new dominant selectable marker for eukaryotes.

PMID- 8159162
TI  - Replication of the Streptomyces plasmid pSN22 through single-stranded
      intermediates.
AB  - The replication of the 11 kb conjugative multicopy Streptomyces plasmid pSN22 was
      analyzed. Mutation and complementation analyses indicated that the minimal region
      essential for plasmid replication was located on a 1.9 kb fragment of pSN22,
      containing a transacting element encoding a replication protein and a cis-acting
      sequence acting as a replication origin. Southern hybridization showed that
      minimal replicon plasmids accumulated much more single-stranded plasmid molecules
      than did wild-type pSN22. Only one strand was accumulated. A 500 bp fragment from
      the pSN22 transfer region was identified which reduced the relative amount of
      single-stranded DNA, when added in the native orientation to minimal replicon
      plasmids. This 500 bp DNA sequence may be an origin for second-strand synthesis.
      It had no effect on the efficiency of co-transformation, plasmid incompatibility,
      or stability. The results indicate that pSN22 replicates via single-stranded
      intermediates by a rolling circle mechanism.

PMID- 8159163
TI  - Chemically induced changes in the spectrum of amplifications of the human
      minisatellite MS1 integrated in chromosome III of a haploid yeast strain.
AB  - To study chemically induced DNA amplifications we used the haploid Saccharomyces
      cerevisiae strain TR(MS1)-1 carrying an integrated chromosomal copy of the human
      minisatellite. MS1. Chemicals with different mechanisms of action were tested in
      this strain: methyl methanesulphonate, ethylene oxide (EO), propylene oxide (PO),
      camptothecin, 2,3,7,8-tetrachlorodibenso-p-dioxin (TCDD) and reserpine. No
      increase in frequency of new MS1 length alleles was seen with any of the tested
      chemicals relative to the spontaneous frequency of approximately 30%. EO and TCDD
      induced changes in the amplification spectrum, i.e., the frequency distribution
      of MS1 length alleles longer than the original 1.42 kb allele. PO and
      camptothecin increased the frequency of plasmid "pop-out" events. It seems likely
      that several mechanisms e.g. unequal exchanges, replication slippage and loop
      formation leading to deletion of a ring of tandem repeats, are involved in the
      generation of new MS1 length alleles. A loop-forming deletion mechanism is
      supported by the tendency to multimodality shown in the deamplification (loss of
      repeat units) spectra, i.e. the frequency distribution of new MS1 length alleles
      shorter than the original allele. EO and TCDD induced "longer" MS1 length alleles
      as compared to the control. The frequent generation of new MS1 length alleles in
      this haploid yeast strain further demonstrates the instability of such sequences
      and their possible relevance to genetic toxicology and the mechanisms of
      induction of cancer as well as other diseases. This study is a first step towards
      the development of an assay for DNA amplification without the use of a selective
      agent.

PMID- 8159164
TI  - A structure-function analysis of NOD, a kinesin-like protein from Drosophila
      melanogaster.
AB  - We have analyzed a collection of 12 mutations in the Drosophila melanogaster nod
      locus, which encodes a kinesin-like protein involved in female meiotic chromosome
      segregation. The kinesin-like domain is at the N-terminus of the protein, while
      the C-terminal portion of the protein is unique. Four of the mutations are
      missense and affect highly conserved domains of the kinesin-like portion of the
      predicted protein, and thus demonstrate that the sequence conservation is
      biologically relevant. Surprisingly, two other mutations, which behave
      genetically as null alleles, are the result of mutations in the last exon of the
      nod gene. Thus, these two mutations affect the most C-terminal residues in the
      unique portion of the predicted protein. Based on these mutations, we suggest
      that this part of the protein may also be essential for wild-type function. The
      mutations were induced by either gamma-rays or ethyl methanesulfonate (EMS). All
      of the gamma-ray induced mutations were small or large chromosomal
      rearrangements, while all of the EMS mutations were G-->A transitions. These
      findings are consistent with the biochemical basis of the mode of action of each
      mutagen.

PMID- 8159165
TI  - The lysozyme locus in Drosophila melanogaster: an expanded gene family adapted
      for expression in the digestive tract.
AB  - Lysozyme has been studied in insects as part of the system of inducible
      antibacterial defence in the haemolymph. We recently found two Drosophila
      lysozyme genes that are constitutively expressed in the digestive tract, and are
      probably involved in the digestion of bacteria in the food. To obtain an overview
      of the lysozyme genes in this species and their possible roles in immunity and
      digestion, we have now characterized all six lysozyme genes in the cloned part of
      the lysozyme locus at 61F, and a seventh gene that maps to the same chromosomal
      location. The expression of the genes follows four different patterns: firstly,
      four closely related genes, LysB, C, D and E, are all strongly expressed in the
      midgut of larvae and adults; secondly, LysP is expressed in the adult salivary
      gland; thirdly, LysS is expressed mainly in the gastric caecae of larvae; and
      finally, LysX is primarily expressed in the metamorphosing midgut of late larvae
      and early pupae. The LysD-like genes and LysS are strongly repressed in
      artificially infected animals, possibly reflecting a malaise reaction in the
      digestive tract. None of the genes is expressed in the fat body or haemocytes.
      Thus rather than being a component of the haemolymph, the Drosophila lysozymes
      are found mainly in the digestive tract where they are expressed at a high level.
      Furthermore all genes, except LysP, encode acidic proteins, in contrast to the
      strongly basic "typical" lysozymes. This is highly reminiscent of the situation
      in ruminants, where the lysozymes have been recruited for the digestion of
      symbiotic bacteria in the stomach.

PMID- 8159166
TI  - Cloning, sequencing and expression of the gene encoding 2-phosphoglycerate kinase
      from Methanothermus fervidus.
AB  - The gene encoding 2-phosphoglycerate kinase (2PGK), which catalyses the first
      step in the biosynthesis of cyclic 2,3-diphosphoglycerate in methanogens, was
      cloned and sequenced from the hyperthermophilic Methanothermus fervidus. The 2pgk
      gene codes for 304 amino acids, corresponding to a relative molecular mass of
      35040. The 2pgk mRNA was estimated to be 1600 nucleotides in size. Putative
      transcription signals and the ribosome-binding site of 2pgk are discussed.
      Production of 2PGK from M. fervidus in Es-cherichia coli reveals the same
      apparent molecular weights for the native enzyme and its denatured subunit as
      those shown by the 2PGK purified from M. fervidus. Also the kinetic parameters of
      2PKG produced in E. coli correspond well with those from the enzyme isolated from
      the natural host M. fervidus.

PMID- 8159167
TI  - Molecular cloning and characterization of the Schizosaccharomyces pombe his3 gene
      for use as a selectable marker.
AB  - A DNA fragment which carries the his3 gene of Schizosaccharomyces pombe has been
      isolated and characterized for use as a selectable marker in transformations. The
      his3 gene encodes the imidazole acetol phosphate transaminase enzyme
      (E.C.2.6.1.9), which is responsible for converting imidazole acetol-P to
      histidinol-P in step 8 of histidine biosynthesis. The nucleotide sequences of a
      2196 bp gene fragment and a corresponding cDNA clone were determined. Three
      intron sequences punctuate the 1451 bp coding region which generates a predicted
      polypeptide of 384 amino acids with a molecular mass of 42736 daltons. Northern
      analysis of his3 mRNAs indicates that the transcript is approximately 1.6 kb in
      size. Steady-state levels are down-regulated by nitrogen limitation but are
      unaffected by histidine starvation. The deduced amino acid sequence was compared
      to the Saccharomyces cerevisiae HIS5, Escherichia coli HisC, and Salmonella
      typhimurium HisC proteins, all of which are imidazole acetol phosphate
      transaminases. The S. pombe his3 protein was 49.5% identical to the S. cerevisiae
      HIS5 protein and 21.5% identity was found when all four proteins were compared.
      The shuttle vector pBG1 was constructed by subcloning the smallest functional
      region of his3 and the S. pombe ars1 sequence into pUC18 for use in
      transformation of His3--S. pombe strains. New S. pombe strains in which the his3
      gene was deleted have also been constructed.

PMID- 8159168
TI  - The Pseudomonas aeruginosa homologs of hemC and hemD are linked to the gene
      encoding the regulator of mucoidy AlgR.
AB  - The algD gene encodes NAD-linked GDPmannose dehydrogenase, which is essential for
      the mucoid phenotype, an important virulence factor expressed by Pseudomonas
      aeruginosa in cystic fibrosis patients. AlgR, a response regulator controlling
      mucoidy, is required for high level expression of algD. Inactivation of algR
      completely abrogates algD expression while mutations immediately downstream of
      algR affect induction of the algD promoter. In order to examine the nature of
      genetic elements located downstream of algR, the complete nucleotide sequence of
      this region was determined. This analysis revealed the presence of two newly
      identified P. aeruginosa genes with predicted gene products homologous to known
      porphobilinogen deaminases (HemC) from other organisms, and uroporphyrinogen III
      cosynthase (HemD) from Escherichia coli. The concerted action of both of these
      enzymes is essential for the synthesis of heme precursors. Mutations within the
      region containing the P. aeruginosa homologs of hemC and hemD affect algD
      promoter activity during growth on nitrate. Furthermore, transcriptional analyses
      indicated that hemC was cotranscribed with algR at detectable levels in mucoid
      cells. These results suggest a link between physiological processes dependent on
      heme and conditions conductive to algD expression and mucoidy.

PMID- 8159169
TI  - Characterization of the genes and attachment sites for site-specific integration
      of plasmid pSE101 in Saccharopolyspora erythraea and Streptomyces lividans.
AB  - The 11.3 kb plasmid pSE101 integrates into the chromosome of Saccharopolyspora
      erythraea at a specific attB site and into the chromosome of Streptomyces
      lividans at many sites. Multisite integration in S. lividans was also observed
      when a 1.9 kb segment of pSE101 containing attP and adjacent plasmid sequence was
      used to transform a pSE101- S. lividans host. Nucleotide sequencing of this
      segment revealed the presence of a complete open reading frame (ORF) designated
      int, encoding a putative polypeptide of 448 amino acids that shows similarities
      to site-specific recombinases of the integrase family. Sequencing of the 1.3 kb
      segment upstream of int revealed the presence of three additional ORFs: the one
      most distal to int encodes a putative 76 amino acid basic polypeptide analogous
      to the Xis proteins of a number of bacteriophages. Nucleotide sequencing of attP,
      and the attB, attL and attR sites from Sac. erythraea revealed a 46 bp sequence
      common to all sites with no duplications of chromosomal sequences in the
      integrated state. A putative structural gene for a tRNA(Thr) was found to overlap
      the 46 bp common sequence at attB. Sequencing of four pSE101 integration sites
      (attB') and corresponding attL' and attR' sites in S. lividans showed that the 46
      bp sequence was present at each attR' site, whereas only the first three bases,
      CTT, were retained at each attL' and attB' site. A feature common to the four
      attB' sites and to attB is a highly conserved 21 bp segment with inverted repeats
      flanking the CTT sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159170
TI  - Isolation and molecular characterization of dTnp1, a mobile and defective
      transposable element of Nicotiana plumbaginifolia.
AB  - By Northern blot analysis of nitrate reductase-deficient mutants of Nicotiana
      plumbaginifolia, we identified a mutant (mutant D65), obtained after gamma-ray
      irradiation of protoplasts, which contained an insertion sequence in the nitrate
      reductase (NR) mRNA. This insertion sequence was localized by polymerase chain
      reaction (PCR) in the first exon of NR and was also shown to be present in the NR
      gene. The mutant gene contained a 565 bp insertion sequence that exhibits the
      sequence characteristics of a transposable element, which was thus named dTnp1.
      The dTnp1 element has 14 bp terminal inverted repeats and is flanked by an 8-bp
      target site duplication generated upon transposition. These inverted repeats have
      significant sequence homology with those of other transposable elements. Judging
      by its size and the absence of a long open reading frame, dTnp1 appears to
      represent a defective, although mobile, transposable element. The octamer motif
      TTTAGGCC was found several times in direct orientation near the 5' and 3' ends of
      dTnp1 together with a perfect palindrome located after the 5' inverted repeat.
      Southern blot analysis using an internal probe of dTnp1 suggested that this
      element occurs as a single copy in the genome of N. plumbaginifolia. It is also
      present in N. tabacum, but absent in tomato or petunia. The dTnp1 element is
      therefore of potential use for gene tagging in Nicotiana species.

PMID- 8159171
TI  - Functional organization of the riboflavin biosynthesis operon from Bacillus
      subtilis SHgw.
AB  - We have sequenced 6006 bp DNA of a region from the Bacillus subtilis SHgw
      chromosome known to contain riboflavin biosynthesis genes (rib gene cluster, 210
      degrees on the B. subtilis genetic map). Five of the seven open reading frames
      found within the sequence are shown to represent the genes ribG, ribB, ribA, ribH
      and ribTD. The calculated molecular masses for the putative translation products
      are 39,305, 23,481, 44,121, 16,287 and 14,574 daltons respectively. The five rib
      genes are transcribed as a polycistronic 4277 nucleotide messenger RNA. The
      steady-state level of the transcript is negatively regulated by riboflavin. A cis
      acting element necessary for regulation was mapped by analysis of constitutive
      mutations within the 5' untranslated region of the operon. The element is at
      least 48 bp in length and does not bear obvious similarity to well defined
      prokaryotic regulatory elements. The molecular mechanism of regulation remains
      unknown, but the data presented argue against regulation by attenuation.

PMID- 8159172
TI  - Sequence and expression of endogenous S-locus glycoprotein genes in self
      compatible Brassica napus.
AB  - Brassica napus is an amphidiploid plant which is self-compatible even though it
      is derived from hybridisation of the self-incompatible species B. oleracea and B.
      campestris. Experiments were undertaken to establish if S-locus glycoprotein
      (SLG) genes exist in B. napus and whether these are expressed as in self
      incompatible Brassica species. Two different stigma-specific cDNA sequences
      homologous to SLG genes were obtained from the B. napus cultivar Westar. One of
      these sequences, SLGWS1, displayed highest homology to class I SLG alleles,
      whereas the other, SLGWS2, showed greatest homology to class II SLG genes. Both
      were expressed at high levels in Westar stigmas following a developmental pattern
      typical of SLG genes in the self-incompatible diploids. We infer that they
      represent the endogenous SLG genes at the two homologous S-loci. The occurrence
      of normally expressed SLG genes and its relevance to the self-compatible
      phenotype of B. napus is discussed.

PMID- 8159173
TI  - Nucleotide sequence of the tryptophan decarboxylase gene of Catharanthus roseus
      and expression of tdc-gusA gene fusions in Nicotiana tabacum.
AB  - The enzyme tryptophan decarboxylase (TDC; EC 4.1.1.28) converts tryptophan into
      tryptamine. In Catharanthus roseus and other plants capable of producing
      terpenoid indole alkaloids (TIAs) TDC links primary metabolism to the secondary
      metabolic pathway involved in the biosynthesis of these compounds. The
      accumulation of tdc mRNA in C. roseus cells is developmentally regulated and
      transcriptionally influenced by elicitors (induction) and auxins (repression).
      Here we report that TDC is encoded by a single copy gene in the C. roseus genome.
      No introns were observed upon isolation and sequencing of this gene. To study
      gene expression controlled by the tdc promoter, a 2 kb promoter fragment and a
      number of 5' deleted promoter derivatives were joined in translational fusion to
      a beta-D-glucuronidase reporter gene (gusA). Expression of the chimaeric
      constructs was monitored in stably transformed tobacco plants and in transiently
      transfected tobacco protoplasts. Histochemical and fluorimetric analysis of
      transgenic plants revealed that 1938 bp of the tdc promoter (with respect to the
      translational start codon) give rise to GUS activity in roots, stems and leaves.
      No tissue or cell type specificity was noted. Promoter deletions up to nucleotide
      -398 directed lower levels of gusA expression but conferred the same pattern of
      staining for GUS activity as the -1938 construct. Further deletion of the tdc
      promoter up to nucleotide -232 resulted in drastically reduced GUS activity
      levels and loss of GUS staining in all parts of the transgenic plants. In
      contrast to stable transformation, the -232 tdc-gusA construct gave rise to GUS
      activity levels comparable to those of the -398 construct in an assay system for
      transient expression in protoplasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159175
TI  - Deletion of the prc (tsp) gene provides evidence for additional tail-specific
      proteolytic activity in Escherichia coli K-12.
AB  - The Escherichia coli protease Prc (Tsp) exhibits specificity in vitro for
      proteins with nonpolar carboxyl termini. To determine whether Prc is responsible
      for the selective degradation in vivo of proteins with nonpolar carboxyl termini,
      we constructed a prc (tsp) deletion strain. Deletion of the prc gene did not
      prevent the rapid intracellular degradation of a variant of the amino-terminal
      domain of lambda repressor with a nonpolar carboxyl terminus, even though this
      protein is a substrate for Prc in vitro. Our results indicate that at least one
      additional carboxy-terminal-specific proteolytic system must exist in E. coli.

PMID- 8159174
TI  - A chimeric gene encoding the methionine-rich 2S albumin of the Brazil nut
      (Bertholletia excelsa H.B.K.) is stably expressed and inherited in transgenic
      grain legumes.
AB  - The coding region of the 2S albumin gene of Brazil nut (Bertholletia excelsa
      H.B.K.) was completely synthesized, placed under control of the cauliflower
      mosaic virus (CaMV) 35S promoter and inserted into the binary vector plasmid
      pGSGLUC1, thus giving rise to pGSGLUC1-2S. This was used for transformation of
      tobacco (Nicotiana tabacum L. cv. Petit Havanna) and of the grain legume Vicia
      narbonensis L., mediated by the supervirulent Agrobacterium tumefaciens strain
      EHA 101. Putative transformants were selected by screening for neomycin
      phosphotransferase (NPT II) and beta-glucuronidase (GUS) activities. Transgenic
      plants were grown until flowering and fruiting occurred. The presence of the
      foreign gene was confirmed by Southern analysis. GUS activity was found in all
      organs of the regenerated transgenic tobacco and legume plants, including the
      seeds. In the legume, the highest expression levels of the CaMV 35S promoter
      controlled 2S albumin gene were observed in leaves and roots. 2S albumin was
      localized in the vacuoles of leaf mesophyll cells of transgenic tobacco. The
      Brazil nut protein was present in the 2S fraction after gel filtration
      chromatography of the legume seed proteins and could be clearly identified by
      immunoblotting. Analysis of seeds from the R2 progenies of the legume and of
      transgenic tobacco plants revealed Mendelian inheritance of the foreign gene.
      Agrobacterium rhizogenes strain RifR 15834 harbouring the binary vector pGSGLUC1
      2S was also used to transform Pisum sativum L. and Vicia faba L. Hairy roots
      expressed the 2S albumin-specific gene. Several shoots were raised but they never
      completely rooted and no fertile plants were obtained from these transformants.

PMID- 8159176
TI  - Topodiagnostic value of brain stem reflexes.
AB  - The masseter and medial pterygoid stretch reflexes, the masseter inhibitory
      reflexes, and the blink reflexes are useful diagnostic tools for evaluation of
      brain stem disorders. The structures mediating these reflexes are largely known.
      Characteristic changes of the normal response patterns due to various lesions
      have been described. Distinct reflex abnormalities indicate lesions at specific
      sites. Multireflex testing improves the accuracy with which localization can be
      made. A number of lesions suspected on clinical data may be confirmed by reflex
      findings only and not by imaging studies. Reflex testing can be utilized to
      demonstrate multiple lesions evoked by a single vascular event and evaluate
      dissemination of central nervous involvement in multiple sclerosis patients.

PMID- 8159177
TI  - Anionic phospholipids calcium binding sites in Duchenne and murine X-linked
      muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) and murine X-linked muscular dystrophy (mdx)
      are genetically homologous and both characterized by absence of dystrophin. The
      function of this protein is not defined nor is the pathogenesis of the severe
      muscle necrosis and progressive weakness found in DMD but not in mdx. Recently we
      found that anionic phospholipid (AP) calcium binding sites are lacking at the
      muscle cell surface in DMD and we correlated these data with dystrophin
      deficiency and muscle necrosis. In order to verify the role of AP lack in the
      pathogenesis of muscle necrosis in DMD we studied the ultrastructural
      localization of these Ca++ receptors in mdx muscle membrane showing that they are
      normally represented as they are in control mouse and normal human muscle. The
      absence of AP in DMD compared with a normal distribution in mdx suggests that
      these calcium binding site alterations play an important and specific role in
      muscle fiber necrosis.

PMID- 8159178
TI  - What is the best diagnostic index of conduction block and temporal dispersion?
AB  - In order to find the best diagnostic index of conduction block and abnormal
      temporal dispersion, the amplitude, duration, and area of the compound muscle
      action potentials (CMAP) were studied in 40 normal controls and 28 patients with
      acquired demyelinating neuropathies. In the normal subjects, there was a
      substantial difference among the various nerves in the degree of CMAP amplitude
      reduction and CMAP duration prolongation with proximal stimulation, and thus
      different criteria should be used for conduction block or abnormal temporal
      dispersion for a given nerve. In 28 patients with demyelinating neuropathy, 58 of
      207 (28%) tested nerve segments showed nerve conduction velocity (NCV) evidence
      of demyelination. To identify "demyelination" in these segments, conduction block
      was best detected by the total area method in 71% of cases, and abnormal temporal
      dispersion was best by the negative-peak duration method. This study showed that
      the best diagnostic index for conduction block is the total area method and for
      abnormal temporal dispersion, the negative-peak duration method.

PMID- 8159179
TI  - Parvalbumin immunocytochemistry and calcium deposition in muscle fiber necrosis
      and subsequent regeneration following intramuscular injection of metoclopramide.
AB  - We have studied the sequential change of parvalbumin immunocytochemistry and its
      correlation with intracellular Ca2+ deposition in an animal model of muscle fiber
      necrosis and regeneration induced by intramuscular injection of metoclopramide.
      Twenty-four hours after the drug's injection, extensive muscle fiber necrosis,
      together with dramatic loss of parvalbumin immunoreactivity and intracellular
      Ca2+ deposition, was observed. Muscle fiber regeneration began on day 4 after the
      injection and was complete by the end of the third week. Parvalbumin was not
      detected in the regenerating fibers, but gradually emerged during the second week
      as muscle fibers increased in size. It can be suggested that loss of parvalbumin
      in necrotic fibers is secondary to the loss in integrity of the sarcolemma.
      Alternatively, loss of parvalbumin in degenerating fibers may impair calcium
      buffering and act as a contributory factor in the necrotic process. The
      progressive appearance of parvalbumin immunoreactivity in regenerating fibers
      parallels that found in normal myogenesis.

PMID- 8159180
TI  - EMG changes in respiratory and skeletal muscles during isometric contraction
      under normoxic, hypoxemic, or ischemic conditions.
AB  - The consequences of general hypoxemia (PaO2 = 51 mmHg) on two muscle groups
      (adductor pollicis and diaphragm) sustaining 80% maximal isometric voluntary
      contraction were studied in healthy individuals. For adductor pollicis,
      contractions were also executed after 10-s or 3-min rest ischemia. Compared to
      control, i.e., normoxic, sustained isometric workloads, significant shortening of
      endurance time occurred only when adductor pollicis contracted under hypoxemic
      conditions. In both muscle groups, a 3-min ischemia test as well as hypoxemia
      reduced the rate of changes in integrated surface EMG in a low frequency band and
      lowered, or did not modify, the rate of change in the high above low frequency
      ratio. Recovery of normal patterns of EMG changes was prolonged only after the
      adductor pollicis contracted under hypoxemic conditions. The present data show
      that both hypoxemia and prolonged rest ischemia reduced the rate of changes in
      quantitative EMG activity, with the more significant effects being measured under
      hypoxemia.

PMID- 8159181
TI  - Sensory neuropathy in infantile onset spinocerebellar ataxia (IOSCA).
AB  - Infantile onset spinocerebellar ataxia with sensory neuropathy is a new,
      inherited multisystem disorder discovered in 19 Finnish patients. In order to
      define the neuropathy of the disease, we measured sensory nerve action potentials
      and nerve conduction velocities in 18 patients, and recorded somatosensory evoked
      potentials (SEP) in 10 patients and performed a sural nerve biopsy in 13
      patients. The fixed and teased nerve fascicles were examined by light and
      electron microscopy, and the whole transverse section of a nerve fascicle was
      photographed and enlarged for morphometric measurements. Our investigation
      revealed an early onset, rapidly progressive axonal neuropathy: the sensory
      action potentials were decreased after the age of 2 and a severe loss of mainly
      large myelinated fibers was found.

PMID- 8159182
TI  - Temperature dependence of nerve conduction and EMG in neuropathy associated with
      gammopathy.
AB  - The effects of warming on nerve conduction variables and electromyography were
      studied in 15 patients with a polyneuropathy associated with monoclonal
      gammopathy of undetermined significance. In each patient median nerve (motor,
      sensory) and tibial nerve (motor) conduction parameters were measured before and
      after warming in water at 36 degrees C. Warming: (1) increased the conduction
      velocity (CV); (2) decreased the distal motor latency, amplitude, and duration of
      the compound muscle or nerve action potential; and (3) caused fibrillations to
      appear in 1 patient. The increase in CV with temperature depended upon the CV
      after warming: the lower this CV, the smaller the increase in CV with temperature
      (delta CV/delta T). Correction of median nerve motor CV before warming with 2.2
      m/s per degree C yielded CV values which were higher than the CV values after
      warming, because in most patients delta CV/delta T was less than 2.2 m/s per
      degree C. Because of differences in delta CV/delta T values, it is more accurate
      to warm the extremity than to correct for temperature.

PMID- 8159183
TI  - Variable effect of calcium channel blockers on the decremental response in
      experimental autoimmune myasthenia gravis.
AB  - We tested the effect of intravenous administration of verapamil and nimodipine on
      the decremental response in rabbits with experimental autoimmune myasthenia.
      Nimodipine produced an immediate augmentation of the decremental response to 3-Hz
      nerve stimulation, which lasted about 30 min. In contrast, verapamil caused
      marked amelioration of the decrement beginning 30 min after injection. Our
      findings are consistent with previous reports suggesting that verapamil has a
      presynaptic effect of enhanced acetylcholine release at the neuromuscular
      junction. Since evaluation of a drug effect in vivo in animals with experimental
      autoimmune myasthenia gravis may be more pertinent to its effect on patients with
      myasthenia gravis (MG), verapamil might prove to be safer in MG than nimodipine.
      However, due to the additional effects of calcium channel blockers, the safety of
      their use in myasthenia gravis cannot be inferred from the experimental results.

PMID- 8159184
TI  - Dystrophin and dystrophin-related protein in the brains of normal and mdx mice.
AB  - To clarify the localization and characterization of dystrophin and dystrophin
      related protein (DRP) in the brains of normal and mdx mice, we carried out
      immunostaining and immunoblotting studies using four region-specific
      antidystrophin and anti-DRP antibodies. With immunostaining, punctate
      immunoreactivity of dystrophin was seen along the cell bodies and dendrites of
      the cerebral cortical neurons in the normal mice. By contrast, dystrophin was not
      detected at all in the brains of mdx mice. Immunoreactivity of DRP was observed
      in the vascular walls, pia mater, and choroid plexus of both normal and mdx
      brains, but not in the neuronal cells. The possible compensatory increase of DRP
      as seen in the skeletal muscles of mdx mice was not noted in the brains. The
      immunoblot findings were very consistent with those of immunostain. Although
      further studies of brain-type dystrophin are necessary, it seems unlikely that
      DRP participates in any physiological function of the neuronal cells.

PMID- 8159185
TI  - H reflex studies in cerebral palsy patients undergoing partial dorsal rhizotomy.
AB  - H reflex studies were performed in ten spastic children with cerebral palsy who
      underwent partial dorsal rhizotomy (PDR). Under anesthesia prior to PDR, H reflex
      amplitude evoked by percutaneous peripheral nerve stimulation gradually declined
      in all patients and became unobtainable in five. Motor responses could still be
      evoked by apparent dorsal root stimulation in these five, but since it was shown
      that they were M responses and not reflexes, PDR was performed randomly. In the
      other five patients, in whom H reflexes were still evokable, dorsal root
      stimulation evoked motor responses which were true reflex responses, and PDR was
      performed "selectively." Compared to preoperative values, postoperative Hmax/Mmax
      ratios declined, but no more so in selective than in random PDR. We conclude that
      current intraoperative methods for selection of "abnormal" dorsal rootlets for
      section may be invalid and may have no bearing on successful outcome, since
      spasticity improves even with random PDR.

PMID- 8159186
TI  - Focal myopathy induced by chronic intramuscular heroin injection.
AB  - A patient developed focal fibrotic myopathy after many years of intramuscular
      heroin use. While such changes have been associated with chronic intramuscular
      injections of pentazocine and meperidine, a similar myopathy resulting from
      chronic intramuscular heroin has not been convincingly described.

PMID- 8159187
TI  - Limited benefit of electrophysiological studies during dorsal rhizotomy.
AB  - Using a formula for standard deviation and several assumptions, the potential
      benefit of electrophysiological recording (ER) during dorsal rhizotomy for
      cerebral palsy is calculated and expressed in a ratio, the electrophysiological
      recording benefit ratio (ERBR). ERBR is approximately 1.1 in most of the
      examples, but other factors may reduce this ratio. Severing an additional rootlet
      appears to be a viable alternative to ER in most of the examples. Advantages of
      dorsal rhizotomy without ER include reduced expense and operative time.
      Prospective studies are recommended to evaluate further the benefit of ER during
      dorsal rhizotomy. If stimulation of dorsal rootlets is abandoned during dorsal
      rhizotomy, stimulation of whole dorsal and ventral roots may still be necessary
      to prevent inadvertent severing of motor fibers.

PMID- 8159188
TI  - HTLV-1 in acquired adult myopathy.

PMID- 8159189
TI  - Myasthenia gravis and vitiligo.

PMID- 8159190
TI  - The intrinsic foot muscles are purely innervated by the tibial nerve ("all tibial
      foot")--an unusual innervation anomaly.

PMID- 8159191
TI  - The relative sensitivities of the axillary and accessory nerves in the diagnosis
      of myasthenia gravis.

PMID- 8159192
TI  - A worldwide study of the Huntington's disease mutation. The sensitivity and
      specificity of measuring CAG repeats.
AB  - BACKGROUND: Huntington's disease is associated with an expanded sequence of CAG
      repeats in a gene on chromosome 4p16.3. However, neither the sensitivity of
      expanded CAG repeats in affected persons of different ethnic origins nor the
      specificity of such repeats for Huntington's disease as compared with other
      neuropsychiatric disorders has been determined. METHODS: We studied 1007 patients
      with diagnosed Huntington's disease from 565 families and 43 national and ethnic
      groups. In addition, the length of the CAG repeat was determined in 113 control
      subjects with a family history of Alzheimer's disease (44 patients),
      schizophrenia (39), major depression (16), senile chorea (5), benign hereditary
      chorea (5), neuroacanthocytosis (2), and dentatorubropallidoluysian atrophy (2).
      The number of CAG repeats was also assessed in 1595 control chromosomes, with the
      size of adjacent polymorphic CCG trinucleotide repeats taken into account.
      RESULTS: Of 1007 patients with signs and symptoms compatible with a diagnosis of
      Huntington's disease, 995 had an expanded CAG repeat that included from 36 to 121
      repeats (median, 44) (sensitivity, 98.8 percent; 95 percent confidence interval,
      97.7 to 99.4 percent). There were no significant differences among national and
      ethnic groups in the number of repeats. No CAG expansion was found in the 110
      control subjects with other neuropsychiatric disorders (specificity, 100 percent;
      95 percent confidence interval, 95.2 to 100 percent). In 1581 of the 1595 control
      chromosomes (99.1 percent), the number of CAG repeats ranged from 10 to 29
      (median, 18). In 12 control chromosomes (0.75 percent), intermediate-sized CAG
      sequences with 30 to 35 repeats were found, and 2 normal chromosomes unexpectedly
      had expanded CAG sequences, of 39 and 37 repeats. CONCLUSIONS: CAG trinucleotide
      expansion is the molecular basis of Huntington's disease worldwide and is a
      highly sensitive and specific marker for inheritance of the disease mutation.

PMID- 8159193
TI  - Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a
      six-week and a nine-month taper period.
AB  - BACKGROUND: The optimal regimen for discontinuing antiepileptic medications in
      children with epilepsy is unknown. METHODS: We randomly assigned 149 children to
      either a six-week or a nine-month period of drug tapering, after which therapy
      was discontinued. Each group was composed of patients who had been seizure-free
      for either two or four years before drug tapering was begun. Most patients were
      receiving one antiepileptic drug; none were taking more than two. The children
      were evaluated periodically during and after the taper period. Sixteen patients
      were lost to follow-up before the beginning of the taper period. Proportional
      hazards regression analysis was used to assess the risk of seizure recurrence
      among the remaining 133 patients. RESULTS: Seizures recurred in 53 patients (40
      percent). The mean duration of follow-up was 39 months (range, 11 to 105) for the
      patients who did not have a recurrence of seizures. Neither the length of the
      taper period (six weeks vs. nine months, P = 0.38) nor the length of time the
      patients were free of seizures before the taper period was begun (two years vs.
      four years, P = 0.20) significantly influenced the risk of seizure recurrence.
      The presence of mental retardation (relative risk, 3.1, 95 percent confidence
      interval, 1.5 to 6.2) or spikes in the electroencephalogram at the time of
      tapering (relative risk, 1.9, 95 percent confidence interval, 1.0 to 3.4)
      increased the risk of seizure recurrence. CONCLUSIONS: The risk of seizure
      recurrence during drug tapering and after the discontinuation of antiepileptic
      drug therapy in children with epilepsy is not different whether the medications
      are tapered over a six-week or a nine-month period.

PMID- 8159194
TI  - Imipramine in patients with chest pain despite normal coronary angiograms.
AB  - BACKGROUND: Ten to 30 percent of patients undergoing cardiac catheterization
      because of chest pain are found to have normal coronary angiograms. Because these
      patients may have a visceral pain syndrome unrelated to myocardial ischemia, we
      investigated whether drugs that are useful in chronic pain syndromes might also
      be beneficial in such patients. METHODS: Sixty consecutive patients underwent
      cardiac, esophageal, psychiatric, and pain-sensitivity testing and then
      participated in a randomized, double-blind, placebo-controlled three-week trial
      of clonidine at a dose of 0.1 mg twice daily (20 patients), imipramine at a dose
      of 50 mg nightly with a morning placebo (20 patients), or placebo twice daily (20
      patients); this treatment phase was compared with an identical period of twice
      daily placebo for all patients (placebo phase). RESULTS: Thirteen (22 percent) of
      the 60 patients had ischemic-appearing electrocardiographic responses to
      exercise, 22 of the 54 tested (41 percent) had abnormal esophageal motility, 38
      of 60 (63 percent) had one or more psychiatric disorders, and 52 of 60 (87
      percent) had their characteristic chest pain provoked by right ventricular
      electrical stimulation or intracoronary infusion of adenosine. During the
      treatment phase, the imipramine group had a mean (+/- SD) reduction of 52 +/- 25
      percent in episodes of chest pain, the clonidine group had a reduction of 39 +/-
      51 percent, and the placebo group a reduction of 1 +/- 86 percent, all as
      compared with the placebo phase of the trial. Only the improvement with
      imipramine was statistically significant (P = 0.03). Repeat assessment of
      sensitivity to cardiac pain while the patients were receiving treatment showed
      significant improvement only in the imipramine group (P = 0.01). The response to
      imipramine did not depend on the results of cardiac, esophageal, or psychiatric
      testing at base line, or on the change in the psychiatric profile during the
      course of the study, which generally improved in all three study groups.
      CONCLUSIONS: Imipramine improved the symptoms of patients with chest pain and
      normal coronary angiograms, possibly through a visceral analgesic effect.

PMID- 8159195
TI  - Brief report: factitious diarrhea detected by measurement of stool osmolality.

PMID- 8159196
TI  - Images in clinical medicine. Acute myocardial infarction and coronary spasm.

PMID- 8159197
TI  - Health insurance status and ambulatory care for children.
AB  - BACKGROUND: Many children in the United States lack health insurance. We tested
      the hypothesis that these children are less likely than children with insurance
      to visit a physician when they have specific conditions for which care is
      considered to be indicated. METHODS: We examined the association between whether
      children were covered by health insurance and whether they received medical
      attention from a physician for pharyngitis, acute earache, recurrent ear
      infections, or asthma. Data were obtained on the subsample of 7578 children and
      adolescents 1 through 17 years of age who were included in the 1987 National
      Medical Expenditures Survey, a national probability sample of the civilian,
      noninstitutionalized population. RESULTS: Uninsured children were more likely
      than children with health insurance to receive no care from a physician for all
      four conditions (unadjusted odds ratios, 2.38 for pharyngitis; 2.04 for acute
      earache; 2.84 for recurrent ear infections; and 1.87 for asthma). Multiple
      logistic-regression analysis was subsequently used to control for age, sex,
      family size, race or ethnic group, region of the country, place of residence
      (rural vs. urban), and household income. After adjustment for these factors,
      uninsured children remained significantly more likely than insured children to go
      without a visit to a physician for pharyngitis (adjusted odds ratio, 1.72; 95
      percent confidence interval, 1.11 to 2.68), acute earache (1.85; 95 percent
      confidence interval, 1.15 to 2.99), recurrent ear infections (2.12; 95 percent
      confidence interval, 1.28 to 3.51), and asthma (1.72; 95 percent confidence
      interval, 1.05 to 2.83). CONCLUSIONS: As compared with children with health
      insurance, children who lack health insurance are less likely to receive medical
      care from a physician when it seems reasonably indicated and are therefore at
      risk for substantial avoidable morbidity.

PMID- 8159198
TI  - Access of Medicaid recipients to outpatient care.
AB  - BACKGROUND: Visits to the emergency department by Medicaid recipients for
      nonemergency problems are common and contribute to rising health care costs.
      However, such patients may have few alternatives. We conducted a telephone survey
      of 953 ambulatory care sites in 10 cities to determine the availability of
      appointments for Medicaid recipients with common problems. METHODS: Research
      assistants telephoned all ambulatory care clinics and a stratified sample of
      private primary care practices in the catchment area served by the hospital
      emergency department in each city. The assistants identified themselves as
      Medicaid recipients seeking care for one of three problems (low back pain,
      dysuria, or sore throat) and asked a standardized series of questions. Data were
      collected on appointments or walk-in visits authorized at any time, within two
      days after the call, or after 5 p.m.; copayment requirements; and reasons
      appointments could not be made. If an appointment was made, it was canceled at
      the end of each call or shortly thereafter. Several weeks later, private-practice
      sites in six of the cities were recontacted; the research assistants identified
      themselves as patients with private insurance and the same problem. RESULTS: An
      appointment or an authorization for a walk-in visit was obtained from 418 of the
      953 practice sites (44 percent); 47 of the sites (5 percent) could not be
      contacted. Appointment rates for the different types of sites ranged from 72
      percent for free-standing urgent care centers to 34 percent for private
      practices. "Not accepting Medicaid" was the most common reason given for not
      granting an appointment or walk-in visit. Only 72 of the sites (8 percent)
      offered after-hours care within two working days after the call without a cash
      copayment. Sixty percent of the 330 private practices that were recontacted
      agreed to see a patient with private insurance within two working days, but only
      26 percent agreed to see a patient with Medicaid within two days (P < 0.001).
      CONCLUSIONS: Medicaid recipients in urban areas have limited access to outpatient
      care apart from that offered by hospital emergency departments.

PMID- 8159199
TI  - The emerging concept of vascular remodeling.

PMID- 8159200
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 20-1994. A five-year-old girl with recurrent cough and fever and
      an enlarging pulmonary mass.

PMID- 8159201
TI  - Setting the record straight in the breast-cancer trials.

PMID- 8159202
TI  - Huntington's disease and repeating trinucleotides.

PMID- 8159203
TI  - Coverage and access in health care reform.

PMID- 8159204
TI  - Departments of medical specialties. A solution for the divergent missions of
      internal medicine?

PMID- 8159205
TI  - We should resist efforts to split internal medicine.

PMID- 8159206
TI  - Fraud in breast-cancer trials.

PMID- 8159207
TI  - Fraud in breast-cancer trials.

PMID- 8159208
TI  - Fraud in breast-cancer trials.

PMID- 8159209
TI  - Fraud in breast-cancer trials.

PMID- 8159210
TI  - Fraud in breast-cancer trials.

PMID- 8159211
TI  - Fraud in breast-cancer trials.

PMID- 8159212
TI  - Fraud in breast-cancer trials.

PMID- 8159213
TI  - The isolation of Cryptococcus neoformans from pigeon droppings and serotyping of
      naturally and clinically sourced isolates in China.
AB  - This is the first report on the isolation of Cryptococcus neoformans from pigeon
      droppings in China and their serotypes. C. neoformans colonies which produced
      brown colonies on caffeic acid-cornmeal agar were found in Twenty-five out of
      thirty-six samples of pigeon droppings. Fifty-one colonies randomly picked from
      the positive samples were identified as C. neoformans by a commercially available
      kit for carbon source assimilation test and Christensen's urea agar. Forty (78%)
      out of the 51 strains were serotyped as A and 11 (22%) as AD. At the same time,
      seventeen out of nineteen clinical isolates were serotyped as A and 2 as B. There
      are three findings in our results. One is that only C. neoformans var. neoformans
      strains could be isolated from pigeon droppings, although the variety gattii
      strains were found in the clinical isolates obtained in the same geographic site
      in China. The second is that serotype A strains were most frequently seen in
      natural and clinical materials in the southeast part of China, and serotype AD
      strains were isolated in pigeon droppings but not in clinical materials. The
      third is that the coexistence of serotype A and AD cells of C. neoformans strains
      in same samples of pigeon droppings were observed.

PMID- 8159214
TI  - Survey of bovine mycotic mastitis in dairy herds in the State of Sao Paulo,
      Brazil.
AB  - The purpose of this study was to isolate fungi from the quarter milk of cow
      udders from several dairy herds and to identify the different genera and species
      involved in mastitis. A total of 2078 milk samples from normal, clinical and
      subclinical mastitis quarters from 22 dairy herds of 16 districts in the State of
      Sao Paulo, Brazil was utilized in this survey. Two hundred and fifty one (12.07%)
      fungi were isolated from the samples. Two hundred and eight of these (82.86%)
      were yeasts and 30 (11.95%) were moulds. The fungi were isolated in pure culture
      (24.77%) or in cultures mixed with bacteria (72.22%). The yeasts isolated were:
      Cryptococcus spp. (71 strains), Rhodotorula spp. (40), Candida spp. (68),
      Trichosporon cutaneum (21), Aureobasidium pullulans (7), and Pichia ohmeri (1).
      Moulds classified in following genera were also isolated: Aspergillus (3),
      Penicillium (3), Alternaria (3), Phoma (3), Epicoccum (2), and Geotrichum (16).

PMID- 8159215
TI  - Turbidimetric and visual criteria for determining the in vitro activity of six
      antifungal agents against Candida spp. and Cryptococcus neoformans.
AB  - The drug concentration which inhibited 50% of growth (IC50), the lowest drug
      concentration at which growth was less than 30% of that in a positive control
      well (IC30), the visual minimal inhibitory concentration (MIC), and the minimum
      fungicidal concentration (MFC), were applied to study the effects of fluconazole,
      itraconazole, ketoconazole, miconazole, flucytosine, and amphotericin B against
      36 isolates of Candida spp. and Cryptococcus neoformans by a broth microdilution
      technique. When the recommendations established by the NCCLS Subcommittee on
      Antifungal Susceptibility Tests were applied for the visual reading of the
      microplates, the results were comparable with those obtained by the turbidimetric
      methods. Differences between MICs and IC30s were observed with miconazole against
      strains of C. glabrata (p = 0.014) and with flucytosine against strains of C.
      neoformans (p = 0.041). Differences between MICs and IC50s were observed with
      fluconazole against strains of C. albicans (p = 0.027), C. tropicalis (p =
      0.046), and C. neoformans (p = 0.041); with miconazole against strains of C.
      glabrata (p = 0.014); and with amphotericin B against strains of C. parapsilosis
      (p = 0.025). Ten additional isolates of C. albicans from AIDS patients suffering
      from recurrent episodes of oral candidiasis and clinically resistant to
      fluconazole also were included in this study. The MICs of fluconazole of these
      strains were significantly higher than those of the control group (p = 0.003).
      When the turbidimetric parameters were applied for testing the in vitro activity
      of fluconazole against the above isolates, both IC30 and IC50 were capable of
      discriminating the strains of the two groups (p = 0.002, p = 0.001,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159216
TI  - Survey of aflatoxins and ochratoxin A in stored tubers of Cyperus esculentus L.
AB  - The mold incidence, moisture contents, pH and levels of mycotoxins (aflatoxins
      B1, G1 and ochratoxin A) on/of/in rootstock snack (tubers of Cyperus esculentus
      L.) samples were monitored during a 150-day storage period. Whereas the mold
      incidence, moisture and mycotoxin levels increased with storage time, the pH
      declined during the same period. Altogether, 12 fungal species, mostly toxigenic,
      including Aspergillus flavus, A. parasiticus and A. ochraceus were isolated. At
      collection period only 3 of the 9 snack samples analysed contained trace amounts
      of aflatoxins. By 120th day, all the 9 samples were contaminated and the average
      levels were 454 and 80 ppb for aflatoxin B1 and aflatoxin G1 respectively on the
      150th day. Ochratoxin A was not detected before 120th day and then only at low
      levels, occurring in a maximum of four-samples and ranging between 10 and 80 ppb.

PMID- 8159217
TI  - Lymphocyte cytotoxicity and erythrocytic abnormalities induced in broiler chicks
      by fumonisins B1 and B2 and moniliformin from Fusarium proliferatum.
AB  - Peripheral blood lymphocytes were isolated from broiler chicks that had ingested
      feed amended with autoclaved Fusarium proliferatum culture material containing
      fumonisin B1 (FB1), fumonisin B2 (FB2) and moniliformin. Lymphocyte viability was
      determined for birds that were placed on amended rations at day 1 or day 7 of age
      at three different levels of mycotoxins, ranging from 61-546 ppm FB1, 14-94 ppm
      FB2 and 66-367 ppm moniliformin. Reduction of the tetrazolium salt, MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], to yield MTT formazan,
      based on mitochondrial metabolic activity, was used to assess cell viability.
      Lymphocyte cytotoxic effects were observed in all treatment groups on day 21;
      chicks that started on amended feed at day 1 of age were affected more than those
      that started at day 7. Abnormal erythrocytes resembling early stages of
      erythroblasts were observed in peripheral blood from test chicks. Abnormally
      shaped red cells (poikilocytes) having a spindle-shape with one or both ends
      pointed were present. Some red cells appeared to be undergoing mitosis. Both
      reduced lymphocyte viability and abnormal erythrogenesis occurred in chicks given
      feed amended with F. proliferatum culture material containing FB1, FB2 and
      moniliformin.

PMID- 8159218
TI  - Fungal flora and mycotoxins of six kinds of nut seeds for human consumption in
      Saudi Arabia.
AB  - A wide range of moulds representing several genera and species, was recorded in
      this study from 5 seed samples of each almond, cashew nut, chestnut, hazelnut,
      pistachio nut and walnut collected from different markets in Ar' Ar, Saudi
      Arabia. The total counts of fungi were widely fluctuated between 1960-7704 and
      1948-7434 colonies/g dry seeds on glucose-Czapek's and glycerol agar media at 28
      degrees C, respectively, and represented twenty genera, 53 species and 2
      varieties of fungi. The prevalent fungi on the 2 agar media were Aspergillus
      flavus, A. niger and Penicillium chrysogenum. On glucose-Czapek's agar, Rhizopus
      stolonifer and Aspergillus flavus var. columnaris were isolated from all 6 kinds
      of nut, A. parasiticus from 5 kinds and A. fumigatus from 4 kinds with high
      frequencies. Eurotium species were completely absent on glucose-Czapek's agar but
      they were isolated in high frequency from all kinds of nut on glycerol agar
      medium. The different nut samples were analyzed by thin layer chromatography for
      the presence of aflatoxins B1, B2, G1 & G2, citrinin, ochratoxins, patulin,
      sterigmatocystin, diacetoxyscirpenol, T-2 toxin and zearalenone. Aflatoxins B1 &
      G1 were detected in 3 out of the 5 samples tested of chestnut at concentrations
      ranging between 20 to 60 micrograms/kg. All other samples of almond, cashew nut,
      hazelnut, pistachio nut, and walnut that were analyzed were mycotoxin free.

PMID- 8159219
TI  - Immunohistochemical characterization of mononuclear cells in delayed
      hypersensitivity reactions to Paracoccidiodes brasiliensis (paracoccidioidin
      test).
AB  - The density and distribution of T cells, T helper cells, macrophages and B cells
      at the site of skin tests with a cytoplasmic Paracoccidioides brasiliensis
      antigen (paracoccidioidin) was studied at 24 and 48 h post-challenge in 10
      patients with the chronic form of paracoccidioidomycosis and in 5 non-infected
      individuals. The in situ study was carried out using immunoperoxidase techniques
      and monoclonal antibodies. The controls showed negative skin test. In the
      patients, the great majority of the cells in the perivascular foci were T cells
      (CD43-positive cells) making up 47% and 48.6% of the total number of cells at 24
      and 48 h respectively. Most of the T cells showed a T helper phenotype (CD45RO
      positive cells). Approximately 25% of the cells were macrophages (CD68-positive
      cells) and there were very few B lymphocytes (CD20-positive cells). The present
      data on the microanatomy of paracoccidioidin skin test sites were consistent with
      a delayed type hypersensitivity pattern. Our results were comparable to those
      reported on skin tests for other granulomatous chronic diseases.

PMID- 8159220
TI  - Occlusive dressings reduce wound infection rates.

PMID- 8159221
TI  - Stomatherapy management of chylous drainage.
AB  - Injuries to the thoracic duct resolve over a period of up to three weeks.
      Reabsorption of chyle occurs spontaneously into the venous system via the left
      subclavian vein. Should this have been damaged, a collateral system will be
      established. If the drainage persists in spite of strict conservative management
      including total parenteral nutrition, exploration of the duct is recommended.

PMID- 8159222
TI  - Planning a career in nursing.

PMID- 8159223
TI  - Supervising patient care.

PMID- 8159224
TI  - A complex problem: academic hospitals and the National Health System. Centre for
      Health Policy.

PMID- 8159225
TI  - [Angelman syndrome].

PMID- 8159227
TI  - Quality improvement.

PMID- 8159226
TI  - Managing mild and moderate chronic asthma--Part 3.

PMID- 8159228
TI  - Eye care train becomes comprehensive primary health care train.

PMID- 8159229
TI  - US agencies split over inquiry into effects of radiation experiments.

PMID- 8159230
TI  - Vaccine programmes facing threat of 'donor fatigue'.

PMID- 8159231
TI  - But are opposed in US Congress.

PMID- 8159232
TI  - Price controls boost innovation in Japan...

PMID- 8159233
TI  - France backs off strict limits on embryo research.

PMID- 8159234
TI  - Health matters in transition.

PMID- 8159235
TI  - Neuroscience. Cajal's rational psychology.

PMID- 8159236
TI  - Evolutionary genetics. Shellfish genes kept in line.

PMID- 8159237
TI  - Immunology. Success in specification.

PMID- 8159238
TI  - Ancient neurofibromatosis.

PMID- 8159239
TI  - Mercury pollution from deforestation.

PMID- 8159240
TI  - Mitochondrial DNA inheritance.

PMID- 8159241
TI  - Mitochondrial DNA inheritance.

PMID- 8159242
TI  - Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the
      number of synaptic release sites.
AB  - Dual intracellular recordings from microscopically identified neurons in the
      hippocampus reveal that the synaptic terminals of three morphologically distinct
      types of interneuron act through GABAA receptors. Each type of interneuron forms
      up to 12 synaptic contacts with a postsynaptic principal neuron, but each
      interneuron innervates a different domain of the surface of the postsynaptic
      neuron. Different kinetics of the postsynaptic effects, together with the
      strategic placement of synapses, indicate that these GABAergic interneurons serve
      distinct functions in the cortical network.

PMID- 8159243
TI  - Formation of amide bonds without a condensation agent and implications for origin
      of life.
AB  - Amide bonds are of central importance for biochemistry; in the guise of peptide
      bonds, they form the backbone of proteins. The formation of amide bonds without
      the assistance of enzymes poses a major challenge for theories of the origin of
      life. Enzyme-free formation of amide bonds between amino acids has been
      demonstrated in the presence of condensing agents such as cyanamide. Here we
      report the formation of amide bonds in aqueous solution in the absence of any
      condensing agent. We find that the formation of pyrite (FeS2) from FeS and H2S
      can provide the driving force for reductive acetylation of amino acids with
      mercaptoacetic acid (HSCH2COOH). The redox energy of pyrite formation permits the
      activation of the carboxylic acid group, which is converted to a species that
      reacts readily with amines. This process provides support for the chemo
      autotrophic theory for the origin of life, in which pyrite formation supplies the
      energy source for the first autocatalytic reproduction cycle.

PMID- 8159244
TI  - Interocular control of neuronal responsiveness in cat visual cortex.
AB  - Neurons in the cat primary visual cortex are selective for particular contour
      orientations but their responsiveness can vary under certain conditions. After
      prolonged stimulation (adaptation), the contrast sensitivity of cortical cells is
      reduced and the 'gain' (the strength of response as a function of contrast)
      falls. The response to an optimal contour is also reduced when a different
      stimulus is superimposed on the receptive field in the same eye. Here we report
      that the sudden appearance of an inappropriate stimulus in one eye can
      interocularly suppress the activity of cortical neurons if they are already
      responding to an optimally oriented stimulus in the other eye. In strabismic
      cats, whose cortical neurons lack binocular facilitation, even contours of
      similar orientation shown to the two eyes trigger such suppression. This
      interocular control of cortical responsiveness could serve to veto signals from
      one eye under conditions that would otherwise cause double vision and perceptual
      confusion.

PMID- 8159245
TI  - Anchoring of protein kinase A is required for modulation of AMPA/kainate
      receptors on hippocampal neurons.
AB  - Phosphorylation of molecules involved in synaptic transmission by multifunctional
      protein kinases modulates both pre- and post-synaptic events in the central
      nervous system. The positioning of kinases near their substrates may be an
      important part of the regulatory mechanism. The A-kinase-anchoring proteins
      (AKAPs; ref. 3) are known to bind the regulatory subunit of cyclic AMP-dependent
      protein kinase A with nanomolar affinity. Here we show that anchoring of protein
      kinase A by AKAPs is required for the modulation of alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-propionic acid (AMPA)/kainate channels. Intracellular
      perfusion of cultured hippocampal neurons with peptides derived from the
      conserved kinase binding region of AKAPs prevented the protein kinase A-mediated
      regulation of AMPA/kainate currents as well as fast excitatory synaptic currents.
      This effect could be overcome by adding the purified catalytic subunit of protein
      kinase. A control peptide lacking kinase-binding activity had no effect. To our
      knowledge, these results provide the first evidence that anchoring of protein
      kinase A is crucial in the regulation of synaptic function.

PMID- 8159246
TI  - Antigen-specific human antibodies from mice comprising four distinct genetic
      modifications.
AB  - Human sequence monoclonal antibodies, which in theory combine high specificity
      with low immunogenicity, represent a class of potential therapeutic agents. But
      nearly 20 years after Kohler and Milstein first developed methods for obtaining
      mouse antibodies, no comparable technology exists for reliably obtaining high
      affinity human antibodies directed against selected targets. Thus, rodent
      antibodies, and in vitro modified derivatives of rodent antibodies, are still
      being used and tested in the clinic. The rodent system has certain clear
      advantages; mice are easy to immunize, are not tolerant to most human antigens,
      and their B cells form stable hybridoma cell lines. To exploit these advantages,
      we have developed transgenic mice that express human IgM, IgG and Ig kappa in the
      absence of mouse IgM or Ig kappa. We report here that these mice contain human
      sequence transgenes that undergo V(D)J joining, heavy-chain class switching, and
      somatic mutation to generate a repertoire of human sequence immunoglobulins. They
      are also homozygous for targeted mutations that disrupt V(D)J rearrangement at
      the endogenous heavy- and kappa light-chain loci. We have immunized the mice with
      human proteins and isolated hybridomas secreting human IgG kappa antigen-specific
      antibodies.

PMID- 8159247
TI  - MHC class I/beta 2-microglobulin complexes associate with TAP transporters before
      peptide binding.
AB  - Major histocompatibility complex class I molecules bind antigenic peptides in the
      endoplasmic reticulum (ER) and transport them to the cell surface for recognition
      by cytotoxic T lymphocytes. The peptides are predominantly generated from
      cytoplasmic proteins, probably by the action of the multicatalytic proteinase
      complex, or proteasome. They are transported into the ER by the transporters
      associated with antigen processing (TAP), a complex formed from two subunits,
      TAP.1 and TAP.2 (refs 3-5). Here we show that the TAP molecules are intimately
      involved in the assembly of the class I/beta 2-microglobulin (beta 2m) peptide
      complex. Free class I heavy chains are associated in the ER with the chaperone
      calnexin. In human B-cell lines, however, class I/beta 2m dimers in the ER are
      physically associated with TAP molecules rather than calnexin. Our results
      suggest that calnexin mediates class I/beta 2m dimerization, and subsequent
      binding of the dimers to TAP molecules facilitates their association with TAP
      transported peptides.

PMID- 8159248
TI  - Cell-cycle calcium transients driven by cyclic changes in inositol trisphosphate
      levels.
AB  - Transient changes in intracellular calcium ([Ca2+]i) have been shown to punctuate
      the cell cycle in various types of cells in culture and in early embryos. The
      [Ca2+]i transients are correlated with cell-cycle events: pronuclear migration,
      nuclear envelope breakdown, the metaphase-anaphase transition of mitosis, and
      cytokinesis. Mitotic events can be induced by injecting calcium and prevented by
      injecting calcium chelators into the sea urchin embryo. Cell-cycle calcium
      transients differ from the transients linked to membrane signal transduction
      pathways: they are generated by an endogenous mechanism, not by plasma membrane
      receptor complexes, and their trigger is unknown. We report here that the
      phosphoinositide messenger system oscillates during the early embryonic cell
      cycle in the sea urchin, leading to cyclic increases in inositol trisphosphate
      that trigger cell-cycle [Ca2+]i transients and mitosis by calcium release from
      intracellular stores.

PMID- 8159249
TI  - [Renal lithium clearance].

PMID- 8159250
TI  - [Uremic pruritus].

PMID- 8159251
TI  - [Diagnostic and therapeutic management of ethylene glycol poisoning. Importance
      of crystalluria. Apropos of a case].
AB  - During the course of a case of ethylene glycol poisoning with ensuing oliguric
      renal failure despite early dialysis, we show the importance of early diagnosis
      of this intoxication in underlined. Characteristics of ethylene glycol poisoning
      are: metabolic acidosis with anion gap (without lactic acidosis or keto-acidosis)
      and high plasma osmolarity. Awaiting the result of blood and urinary toxic
      values, crystalluria, by typical needle monohydrate calcium oxalate crystals
      finding, evokes the diagnosis and permits to start a specific treatment. This
      treatment is based on: principles of intensive care, ethanol administration (or 4
      methyl-pyrazole now available), also thiamine and pyridoxine administration and
      finally, dialysis therapy. We can hope, with early and intensive management of
      this poisoning, to prevent the renal failure, principal complication of ethylene
      glycol ingestion, which can lead to chronic renal failure. Therefore,
      crystalluria, an easy and specific diagnosis technic, is of great interest.

PMID- 8159252
TI  - [Definitive end-stage chronic kidney failure after cisplatin treatment].
AB  - Renal failure secondary to CDDP is due to acute tubular necrosis and is usually
      reversible. We report 4 cases of definitive renal failure secondary to
      administration of cisplatin (CDDP). Three women and one man, mean age 40 +/- 8
      years (24 to 64 years), at onset of dialysis are reported. They had received 1 to
      4 courses of CDDP for an endometrial carcinoma (n = 2), a breast carcinoma or a
      thymoma. The mean total dose of CDDP was 447 +/- 169 mg (160 to 900 mg). There
      was no additional nephrotoxic drug. Before treatment serum creatinine
      concentration was normal (77 +/- 7 mumol per liter) in all patients. In 2 cases
      dehydration (due to vomiting and use of mannitol) occurred during CDDP treatment.
      One patient was treated 30 days after a nephrectomy. At the onset of dialysis,
      renal ultrasound was normal. In 3 cases dialysis was necessary within 15 days
      following chemotherapy. In one case renal function deteriorated progressively to
      end stage renal failure 12 months after CDDP treatment. Dialysis was performed in
      3 cases by hemodialysis and in one patient by peritoneal dialysis. All patients
      remained more than 6 months on dialysis. Three patients died from their cancer.
      One patient, being considered cured from his thymoma, is currently being
      evaluated for a kidney transplantation. Our observations outline the potential
      severity of CDDP nephrotoxicity. Systemic hydration with serial serum creatinine
      measurements are mandatory during and after CDDP administration these patients.

PMID- 8159253
TI  - [Clinical value of studying hematuria using phase-contrast microscopy].
AB  - To evaluate the examination of urine erythrocytes with a contrast phase
      microscope for the etiological diagnosis of haematuria (erythrocytes > 10/mm3 of
      non centrifuged urine) the charts of 84 patients with haematuria were reviewed. A
      nephrological origin had been established with certainty in 56 cases with a renal
      biopsy and an urological origin was also established with certainty in 28 cases
      thanks to appropriate radiological, endoscopical and pathological examinations.
      The morphological criteria of the erythrocytes deformation were those of Birch
      and Fairley but the quantitative criteria of these authors (either 80 or 100%)
      were found to be of no value. By successive approaches the threshold of 20% of
      deformed erythrocytes was selected and found to be the best criterion for
      diagnosing glomerular hematuria: the sensitivity of the test is then 73% and its
      specificity 60%. As these results were relatively modest, conditions which
      decrease the percentage of deformed erythrocytes were excluded to improve the
      sensitivity, such as macroscopic haematuria and also examinations made during the
      6 hours following furosemide administration whereas conditions which increase the
      percentage of deformed erythrocytes and which are easily diagnosed such as
      urinary infections, lithiasis and renal insufficiency associated with an uropathy
      were excluded in order to improve the specificity. Then the examination has a
      sensitivity and a specificity of 90% which makes it clinically relevant,
      authorizing a wait and see attitude in case there is an isolated microscopic
      haematuria of glomerular type.

PMID- 8159254
TI  - [Arteriovenous fistula complicated by "fat arm" caused by proximal venous
      occlusion--salvage by axillo-jugular crossing bypass].
AB  - Although subclavian vein cannulation is more and more avoided for temporary
      angioaccess in hemodialysis patients may still now present stenosis or thrombosis
      of this catheterized central vein. Complications may appear, sometimes severe,
      after creation of an ipsilateral arteriovenous fistula. It is important to treat
      them but also to conserve the new created vascular access, in order to maintain
      these patients as long as possible on hemodialysis treatment. According to the
      circumstances, different procedures are used, and among them, the axillary
      contralateral internal jugular vein crossing bypass as here reported.

PMID- 8159255
TI  - Amyloid plaques in cerebellar cortex and the integrity of Purkinje cell
      dendrites.
AB  - We probed serial and near serial sections of cerebellum from 13 Alzheimer's
      disease (AD), 10 older Down's syndrome (DS) patients, and 9 age-matched, non-AD
      controls, using single and double labeling immunohistochemistry to investigate
      the pathologic consequences of beta-amyloid or A4 (A beta) deposits in cerebellum
      and their relationship to Purkinje cells (PCs). Our data showed that A beta
      deposits in cerebellum of AD and older DS adults only form diffuse or preamyloid
      plaques and the density of A beta lesions per unit area of molecular layer
      correlated with the number of PCs per unit length of the subjacent PC layer in
      double immunostained sections (r = 0.85; p < 0.001). About 65% of these
      cerebellar A beta deposits were in physical contact with PC dendrites. No A beta
      plaques were found in the cerebellum of controls. Despite the abundance of A beta
      deposits in the cerebellar cortex of AD and older DS patients, neither PC bodies
      nor PC dendrites in physical contact with A beta lesions showed evidence of
      structural abnormalities.

PMID- 8159256
TI  - Mass and physical dimensions of two distinct populations of paired helical
      filaments.
AB  - We studied the ultrastructure of two fractions of paired helical filaments (PHF)
      from Alzheimer brains separated on sucrose density gradient. Fraction A2 (1M
      sucrose) contained filaments which were short in length and did not aggregate
      while those in fraction AL2 (1/1.5 M sucrose interface) were mostly aggregated.
      By scanning transmission electron microscopy, PHF in fraction A2 had
      significantly more mass per nm length of filament (107-120 kD/nm) than those in
      fraction AL2 (79-85 kD/nm), and they were also wider in their maximum and minimum
      widths but did not differ in their periodicity. Differences in mass and
      dimensions between two morphologically distinct populations of PHF suggest that a
      partial proteolysis may be involved in the generation of the aggregated
      population of PHF. The results suggest that a similar process may be active in
      the formation of neurofibrillary tangles.

PMID- 8159257
TI  - Increased accumulation of cAMP in cerebral microvessels in Alzheimer's disease.
AB  - The objective of this study was to compare the adenylyl cyclase-cAMP second
      messenger system in cerebral microvessels isolated from Alzheimer's patients to
      that in microvessels from nondemented elderly controls. To evaluate the role of
      aging separate from the effects of dementia, microvessels from young and aged
      rodents were also examined. The results of this study indicated that microvessels
      isolated from autopsy material can be used to evaluate adenylyl cyclase activity.
      The data showed that cAMP levels, as an index of adenylyl cyclase activity, are
      significantly (p < 0.02) elevated in microvessels from Alzheimer's disease
      compared to nondemented elderly controls. Stimulation of adenylyl cyclase by
      forskolin was comparable in both groups of microvessels. A comparison of
      unstimulated microvessels from young and aged rodents yielded no significant
      difference in cAMP levels. These results indicate an increased level of cAMP in
      the microvessels of Alzheimer's patients with no age-related change demonstrable
      in rat microvessels.

PMID- 8159258
TI  - Alterations of cerebral metabolism in probable Alzheimer's disease: a preliminary
      study.
AB  - Previous in vitro and in vivo 31P MRS studies of Alzheimer's disease patients
      have revealed alterations in membrane phospholipid metabolism and PET studies
      have shown alterations in glucose and oxidative metabolism. This study of
      probable Alzheimer's disease patients demonstrates severity dependent alterations
      in measures of both high-energy phosphate and membrane phospholipid metabolism.
      Mildly demented Alzheimer's patients compared to the controls, have increases in
      the levels of phosphomonoesters, decreases in the levels of phosphocreatine and
      probably adenosine diphosphate, and an increased oxidative metabolic rate. As the
      dementia worsens, the levels of phosphocreatine and adenosine diphosphate
      increase, the levels of phosphomonoesters decrease, and the oxidative metabolic
      rate decreases. The phosphomonoester findings replicate previous findings and
      provide a new dimension to the molecular pathology of Alzheimer's disease,
      implicating basic defects in membrane metabolism. The changes in oxidative
      metabolic rate suggest the AD brain is under energetic stress. The changes in
      energy metabolites with increasing dementia could be a consequence of nerve
      terminal degeneration and are consistent with previous PET findings. 31P MRS
      provides new diagnostic and metabolic insights into this disease and would be a
      noninvasive method to follow the progression of the disease and the metabolic
      response to therapeutic interventions.

PMID- 8159259
TI  - Analysis of magnetic resonance spectra by mole percent: comparison to absolute
      units.
AB  - A variety of metabolites present in perchloric acid extracts of brain tissue were
      measured by 1H and 31P magnetic resonance spectroscopy (MRS) and HPLC in the same
      tissue sample and the MRS results were expressed both in terms of mole % and
      mumole/g based on an internal standard. The levels of 16 metabolites were
      compared by linear regression analysis and the mole % results were found to
      correlate very well with the results expressed as mumole/g. To compare the two
      units under typical experimental conditions, the percent change in metabolites in
      a group of Alzheimer's disease brains was compared to a control group using both
      units. The results were essentially identical for the mole % and mumole/g
      methods. We conclude that the use of the mole % method of expressing MRS data
      yields results which are equivalent to those expressed in absolute units and
      suggest that, for in vivo MRS studies, use of the mole % method is preferable
      because fewer artifacts, such as partial volume effects, are introduced.

PMID- 8159260
TI  - Relationship between serum alpha 1-antichymotrypsin and Alzheimer's disease.
AB  - We obtained serum samples and measured alpha 1-antichymotrypsin (ACT) levels in
      36 pairs of consecutive probable Alzheimer's disease (AD) patients and age- and
      sex-matched, cognitively intact control subjects. Serum ACT was measured by
      radial immunodiffusion. Unique to this study, we found that ACT levels rose
      significantly with age within controls (but not within AD cases), thus ACT may be
      related to the aging process. Consistent with other reports, we found that AD
      cases had greater serum ACT in 27 of 36 pairs [mean difference = 135.5 (SE =
      50.8) mg/l (p < 0.05)]. Severity and duration of AD were not significantly
      associated with the observed difference. The ACT increase observed in AD is not
      sufficient to recommend ACT's use as a diagnostic marker for AD. Because adult
      Down's syndrome (DS) persons are known to have pathologic features of AD, we also
      measured serum ACT levels in 11 adult, noninstitutionalized, DS persons paired
      with 11 age- and sex-matched, volunteer control subjects; we found no
      statistically significant difference. The unexpected age-associated increase in
      ACT among normal controls could be an indicator of early amyloid plaque
      formation. Future studies comparing ACT levels in both serum and cerebrospinal
      fluid should help to clarify the origin of ACT found in amyloid plaques and its
      value as a diagnostic marker for AD.

PMID- 8159261
TI  - Visual cortex in Alzheimer's disease: occurrence of neuronal death and glial
      proliferation, and correlation with pathological hallmarks.
AB  - Visual areas 17 and 18 were studied with morphometric methods for numbers of
      neurons, glia, senile plaques (SP), and neurofibrillary tangles (NFT) in 13 cases
      of Alzheimer's disease (AD) as compared to 11 controls. In AD cases, the mean
      neuronal density was significantly decreased by about 30% in both areas 17 and
      18, while the glial density was increased significantly only in area 17. The
      volume of area 17 was unchanged in AD cases but its total number of neurons was
      decreased by 33% and its total number of glia increased by 45% compared to
      controls. In AD the number of SP was similar in areas 17 and 18, while that of
      NFT was significantly higher in area 18. The number of neurons with NFT was only
      2% in area 17 and about 10% in area 18. The discrepancy between the loss of
      neurons and the amount of NFT suggests that neuronal loss can occur without
      passing through NFT degeneration. The deposition of SP was correlated with glial
      proliferation, but not with neuronal loss or neurofibrillary degeneration.

PMID- 8159262
TI  - Neuron loss and shrinkage in the amygdala in Alzheimer's disease.
AB  - Total neuron numbers in the amygdala and in eight of its subnuclei were
      determined in 9 cases of Alzheimer's disease (AD) and in 6 age-matched controls
      (AMC). Total neuron numbers were obtained using the fractionator. A neuron loss
      of 56.3% for the left amygdala and 50.5% for the right amygdala in AD was found,
      being more severe than previously reported. The subdivisions showed a
      differential neuron loss ranging from 35.5% in nucleus lateralis of the right
      amygdala to 70.4% in the nucleus basalis accessorius of the right amygdala.
      Moreover, a shift in size distribution to smaller neurons could be demonstrated.
      No left-right hemispheric differences were detected in total neuron numbers in AD
      and AMC.

PMID- 8159263
TI  - Chronic nimodipine treatment in aged rats: analysis of motor and cognitive
      effects and muscarinic-induced striatal dopamine release.
AB  - Nimodipine is a calcium channel blocker reported to have beneficial effects on
      treatment of ischemic damage as well as the potential for retarding aspects of
      brain and behavioral aging when provided chronically to rats. We treated aged
      male F-344 rats (24 months) with nimodipine in SC pellets in the following doses:
      0 (controls), 20 mg (low-dose), or 40 mg (high-dose) replenished after 6 weeks.
      After 3 months of treatment, surviving rats and a group of young controls (6
      months) were tested in a behavioral battery involving exploratory activity in an
      open field and in a runwheel cage as well as motor abilities required for
      remaining on an inclined screen, suspended from a wire, and balanced on a
      rotorod. Rats were also pretrained for one-way active avoidance in a straight
      runway before being trained in a 14-unit T maze. During 20 trials rats were
      required to negotiate each of 5 maze segments within 10 s to avoid foot shock
      (0.8 mA). Nimodipine treatment produced no significant effects on body weight,
      food intake, or survival of aged rats. Analysis of behavioral results indicated
      significant age-related decline in performance of all tasks except in open-field
      behavior. Nimodipine treatment had no significant effects on behavioral
      performance of aged rats except in maze learning. Rats on the high-dose regimen
      performed significantly better than aged controls in the maze. The results
      indicate that chronic nimodipine treatment of aged rats had no toxic effects and
      might be beneficial for preventing age-related decline in learning performance.

PMID- 8159264
TI  - Effects of peroxidation and aging on rat neocortical ACh-release and protein
      kinase C.
AB  - Cerebral cortical synaptosomes were prepared from 2- or 24-month-old Fischer 344
      rats and exposed to a peroxidizing condition (50 microM ferrous ions and 2 microM
      ascorbate ions) before measuring either the release of newly synthesized
      [3H]acetylcholine (ACh) or protein kinase C activity (PKC). Several secretagogues
      with different mechanisms of action and different responses to aging were used to
      trigger release: K+ depolarization (5 mM-60 mM), calcium ionophore A23187 (1-10
      micrograms/ml), and 4-aminopyridine (0.1-10 mM). Aging reduced K+ depolarization
      induced release at every K+ concentration studied, reduced A23187-induced release
      at low but not high concentrations and did not affect 4-aminopyridine-induced
      release. Membrane peroxidation of synaptosomes from 2-month-old rats altered the
      response to secretagogues to match that seen in 24-month-old rats. Membrane
      peroxidation also attenuated the A23187-stimulated translocation of free to bound
      synaptosomal PKC activity in 2-month-old but not 24-month-old animals. These
      results suggest that membrane peroxidation may mimic some age-related deficits in
      secretagogue-induced [3H]ACh release.

PMID- 8159265
TI  - Chronic administration of flumazenil increases life span and protects rats from
      age-related loss of cognitive functions: a benzodiazepine/GABAergic hypothesis of
      brain aging.
AB  - Under barrier condition and with ad lib access to food and water, 20 Fischer-344
      rats were chronically treated for 10 months with the benzodiazepine (BDZ)
      antagonist, flumazenil (FL; 4 mg/kg/day in drinking water acidified to pH = 3.0),
      beginning at the age of 13 months, while the group of 20 control age-matched rats
      received plain acidified water. The life span of the first 8 deceased rats
      treated with FL was significantly longer than that of the first 8 deceased rats
      in the age-matched control group. In tests for spontaneous ambulation and
      exploratory behavior in the Holeboard apparatus, conducted during the 3rd and the
      8th month of treatment, the FL group, relative to controls, had significantly
      higher scores for the ambulation and exploratory behavior. In tests for
      unrewarded spontaneous alternation in the T maze, conducted at days 7, 39, 42,
      and 47 through 54 after drug withdrawal, i.e., at the age of 24-25 months, the FL
      exposed group, compared to age-matched controls, showed a significantly higher
      percent of alternating choices, a behavior that was statistically comparable to
      that of the "young" 6-month-old controls. In the Radial Maze tests conducted 2
      months after drug withdrawal, the FL group made significantly less "working
      memory" errors and "reference memory" errors, relative to the age-matched 25
      month-old control group, a performance that was comparable to that of the young 7
      month-old control group. In conclusion, chronic FL significantly protected rats
      from age-related loss of cognitive functions. It is postulated that the age
      related alterations in brain function may be attributable to the negative
      metabolic/trophic influences of the "endogenous" benzodiazepine (BDZ) ligands
      and/or those ingested with food. A BDZ/GABAergic hypothesis of brain aging has
      been formulated which assumes that age-related and abnormally strong
      BDZ/GABAergic influences promote neurodegeneration by suppressing trophic
      functions of the aminergic and peptidergic neurons through opening of chloride
      channels in soma membrane and axon terminals, causing excessive hyperpolarizing
      and depolarizing inhibition, respectively. The review of human clinical and
      animal data indicates that FL has nootropic actions by enhancing vigilance
      cognitive and habituation processes.

PMID- 8159266
TI  - Quantitative EEG correlates of cognitive deterioration in the elderly.
AB  - We report on the quantitative analysis of the EEG (QEEG), using the Neurometric
      method, in large samples of normal elderly; normal subjectively impaired elderly;
      patients with mild cognitive impairment; patients presenting with a continuum of
      primary cognitive deterioration from mild to moderately severe as measured by the
      Global Deterioration Scale (GDS), compatible with dementia of the Alzheimer's
      type (DAT). Neurometric QEEG measures were found to be a sensitive index of
      degree of cognitive impairment, especially reflected in increased absolute and
      relative power in the theta band, with delta increasing in later stages of
      deterioration. While these abnormalities were widespread, neither localized or
      lateralized, MANOVA's for GDS and relative power in theta reached highest
      significance in a bilateral temporo-parietal arc. A possible relationship between
      hippocampal dysfunction, cognitive deterioration, and theta abnormalities is
      discussed in relation to these findings. The results suggest that Neurometric
      QEEG features are sensitive to the earliest presence of subjective cognitive
      dysfunction and might be useful in the initial evaluation of patients with
      suspected dementia, as well as in estimating the degree of cognitive
      deterioration in DAT patients.

PMID- 8159267
TI  - Impaired supersensitivity to morphine following chronic naltrexone treatment in
      senescent rats.
AB  - Chronic administration of opiate antagonists produces an increase in the density
      of opiate receptors, as well as an enhanced sensitivity to the analgesic and
      locomotor depressant effects of morphine. The present study assessed whether
      aging alters these regulatory processes. Young (3-4 months), middle-aged (10-11
      months), and senescent (25-30 months) rats were implanted subdermally with slow
      release naltrexone pellets or were given sham surgery. The pellets were removed
      10 days later. Twenty-four hours after pellet removal, morphine-induced (5 mg/kg,
      SC) analgesia and locomotor activity were assessed. Young and middle-aged rats
      treated with naltrexone showed enhanced sensitivity to the analgesic and
      locomotor activity depressant effects of morphine relative to age-matched
      controls. In contrast, senescent rats treated with naltrexone did not differ from
      age-matched controls in their response to morphine. The density of opiate
      receptors labeled with 3H-naloxone was measured in the anterior striatum. Both
      young and senescent rats treated with naltrexone exhibited an increase in opiate
      receptor density relative to age-matched controls. The results indicate that
      senescent rats are capable of up-regulating opiate receptors following chronic
      naltrexone treatment but do not exhibit the corresponding functional
      supersensitivity to morphine.

PMID- 8159268
TI  - A decrease in serum sialyltransferase levels in Alzheimer's disease.
AB  - A reliable antemortem serum marker for Alzheimer's disease (AD) would be of great
      importance for the early detection and subsequent therapeutic management of the
      disease. We have noted a significant decrease in serum levels of the soluble form
      of the sialyltransferase enzyme in a group of AD patients when compared with both
      age-matched elderly (over 60 years) and young (under 60 years) controls. In a
      population of Down's syndrome patients, who develop AD pathology with increasing
      age, there was an age-related decrease in serum sialyltransferase activity in
      patients from 20 to 60 years to approach enzyme levels similar to those observed
      in the AD group. This significant decrease in serum sialyltransferase levels
      observed may both prove a useful peripheral early biochemical marker of
      neurodegeneration and provide an indication of the underlying cellular events
      that occur during the process of nerve cell death in AD.

PMID- 8159269
TI  - Interrelationship between thyroxine and estradiol on the secretion of thyrotropin
      releasing hormone and dopamine into hypophysial portal blood in ovariectomized
      thyroidectomized rats.
AB  - Effects of thyroxine (T4) on the secretion of thyrotropin-releasing hormone (TRH)
      and catecholamines into hypophysial portal blood and on the concentrations of
      arterial plasma thyroid-stimulating hormone (TSH) and prolactin (PRL) in
      ovariectomized and thyroidectomized (Ovx-Tx) rats were studied. Immediately after
      ovariectomy, rats were Tx or sham Tx. The Ovx-Tx rats were injected
      subcutaneously with estradiol benzoate (EB, 0.5 microgram/kg b.w.) or sesame oil,
      and T4 (20 micrograms/kg b.w.) or saline once daily for 2 weeks. The Ovx rats
      with intact thyroid gland were injected with saline and oil only. The hypophysial
      portal blood samples were collected and mixed with or without 2,3
      dimercaptopropanol before extraction by methanol or perchloric acid,
      respectively. The femoral arterial blood was also collected. The concentrations
      of TRH in methanol-extracted portal plasma and that of TSH and PRL in arterial
      plasma were measured by radioimmunoassay. The concentrations of catecholamines in
      perchloric acid-extracted portal plasma samples were measured by radioenzymatic
      assay. Thyroidectomy in Ovx rats resulted in an increase in portal plasma TRH and
      arterial plasma TSH. Despite the presence or absence of estradiol, T4 replacement
      in Ovx-Tx rats decreased portal plasma TRH and arterial plasma TSH to euthyroid
      levels. Combination of the injection of T4 and EB in vivo caused significantly
      decreased levels of portal plasma dopamine and increased arterial plasma PRL
      compared with those in vehicle-injected Ovx-Tx animals. Concentrations of neither
      norepinephrine nor epinephrine in hypophysial portal plasma paralleled the
      altered concentrations of PRL or TSH in arterial plasma.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8159270
TI  - IL-1 beta potentiates the acetylcholine-induced release of vasopressin from the
      hypothalamus in vitro, but not from the amygdala.
AB  - In addition to the magnocellular hypothalamic nuclei, arginine vasopressin (AVP)
      containing neurons have also been identified in limbic structures, including the
      hippocampus and amygdala. In the present study, we compared the qualitative
      properties of the in vitro release of AVP from the dissected hypothalamus with
      the in vitro release from the dissected amygdala and used these release systems
      to evaluate the interactions with neurotransmitters and cytokines. The areas of
      the paraventricular nucleus and supraoptic nucleus that contain the AVP neurons
      and that receive cholinergic innervation are also interleukin (IL)-1 beta
      immunoreactive. Acetylcholine or high KCl (60 mM) induces AVP release in both
      regions, and the AVP release is calcium dependent. Acetylcholine-induced AVP
      release is antagonized by atropine or mecamylamine, indicating that both
      muscarinic and nicotinic receptors are mediating the cholinergic effect in these
      brain regions. IL-1 beta (100 U/ml) had no effect on the basal AVP release from
      the hypothalamus, but significantly potentiated the acetylcholine-induced AVP
      release, lowering the threshold from 500 to 100 nM. This effect was completely
      blocked in the presence of neutralizing antibodies to IL-1 beta, atropine (10
      microM) or mecamylamine (10 microM). IL-6, like IL-1 beta, also potentiated
      acetylcholine-induced AVP release, but to a lesser extent. Neither tumor necrosis
      factor-alpha nor interferon-gamma had any effect on the basal or acetylcholine
      induced AVP release from the hypothalamus. None of the cytokines tested had any
      effect on the basal or acetylcholine-induced AVP release from the amygdala. Our
      results suggest a hypothalamic site of action of IL-1 beta and IL-6 on the
      acetylcholine-induced AVP release. The stimulatory effects of IL-1 and IL-6 on
      adrenocorticotropin release have been ascribed to an increased release of
      corticotropin-releasing factor (CRF). These data further suggest that, in
      addition to CRF, AVP plays a role in the bidirectional communication between
      neuroendoc ine and immune systems. Understanding the mode of interaction between
      IL-1 beta and IL-6 with AVP could clarify pathophysiologic or toxic effects of
      high brain levels of these cytokines.

PMID- 8159272
TI  - Androgen inhibits the increases in hypothalamic corticotropin-releasing hormone
      (CRH) and CRH-immunoreactivity following gonadectomy.
AB  - To characterize the effect of androgens on the hypothalamo-pituitary-adrenal
      (HPA) axis we examined the regulation of corticotropin-releasing hormone (CRH)
      following gonadectomy and hormone replacement. Three-month-old male Fischer 344
      (F344) rats were gonadectomized (GDX) or sham GDX. Control animals remained
      intact. Animals were sacrificed 1, 4, 7, 10, or 21 days following surgery. GDX
      rats had significantly elevated (p < 0.05) levels of hypothalamic CRH 21 days
      after surgery compared to intact and sham-operated rats. In a second study, 3
      month-old male F344 rats were GDX and treated with the non-aromatizable androgen,
      dihydrotestosterone (DHT), using a Silastic capsule containing crystalline DHT
      propionate subcutaneously implanted in each animal's back. Control animals were
      GDX and sham-treated or left intact (INT). Three weeks following gonadectomy, CRH
      levels in the hypothalamus of GDX rats showed a significant increase (p < 0.05)
      compared to intact animals. DHT treatment, beginning at the time of gonadectomy
      prevented this increase. CRH or arginine vasopressin (AVP) immunoreactivity was
      examined using immunocytochemistry. The number of CRH-immunoreactive (IR) cells
      in the paraventricular nucleus (PVN) of GDX, DHT-treated animals was
      significantly decreased (p < 0.05) compared to GDX rats. No differences were seen
      between treatment groups in CRH-IR cell numbers in the bed nucleus of the stria
      terminalis or the central amygdaloid nucleus or in AVP-IR cell numbers in the
      PVN. These data demonstrate that long-term castration increases hypothalamic CRH
      content and CRH-IR cell numbers in the PVN by removal of an androgen-dependent
      repression.

PMID- 8159271
TI  - Effect of cysteamine injection on vasopressin and oxytocin biosynthesis in rat
      hypothalamus.
AB  - Cysteamine (CSH), a sulfhydryl agent that promotes disulfide-exchange reactions,
      was studied for its effects on the immunoreactive (IR) levels and synthesis of
      oxytocin and vasopressin in the hypothalamus. CSH injection (300 mg/kg s.c.)
      caused a rapid (1 h) suppression of 35S-cysteine incorporation into hypothalamic
      arginine vasopressin (VP) and oxytocin (OT). The reduction in labeling persisted
      for about 8 h; label incorporation was normal within 10 h of CSH administration.
      The drug did not influence 35S-cysteine incorporation into acid-precipitable
      protein, nor did it influence 35S-cysteine specific activity in the hypothalamus.
      In addition, 35S-VP and 35S-OT molecules could not be recovered from hypothalami
      of CSH-treated rats by subjecting samples to denaturing, reducing and then
      reoxidizing conditions. Despite the reduction in peptide labeling, CSH treatment
      produced no alterations in the IR VP and OT contents of hypothalamus or posterior
      pituitary. These results indicate that CSH causes a true suppression of both VP
      and OT formation in hypothalamus, and suggest that the effect is either too
      transient to promote a reduction in endogenous stores of either peptide, or that
      the drug equally inhibits peptide production and removal (i.e., axonal transport,
      secretion).

PMID- 8159273
TI  - A time course of altered thyroid states on the noradrenergic system in rat brain
      by quantitative autoradiography.
AB  - The present study was designed to investigate the time course of alterations in
      beta 1- and beta 2-adrenoceptor subtypes, alpha 2-adrenoceptors and uptake sites
      for norepinephrine in the rat brain following thyroidectomy (TXT) and thyroxine
      replacement. The results indicate that alterations in the thyroid state lead to
      changes in the pre- and postsynaptic noradrenergic system that are both region-
      and receptor-specific. TXT caused the binding of 125-iodopindolol to beta 1
      adrenoceptors to decrease in the cortex and hippocampus and caused its binding to
      beta 2-adrenoceptors to decrease in the hypothalamus. TXT caused 3H-idazoxan
      binding to alpha 2-adrenoceptors to be reduced specifically in the amygdala.
      Following TXT, the binding of 3H-nisoxetine to norepinephrine uptake sites was
      found to be increased in the hippocampus and decreased in the hypothalamus. In
      most brain regions, thyroxine replacement for 7 or 28 days caused radioligand
      binding to recover to control levels. Thus it appears that a neuromodulatory link
      between thyroid hormone and the noradrenergic system exists in many regions of
      the rat brain.

PMID- 8159274
TI  - Effect of 5,7-dihydroxytryptamine, ovariectomy and gonadal steroids on serotonin
      receptor binding in rat brain.
AB  - Quantitative autoradiography was used to assess alterations in serotonin (5-HT)
      receptor binding in the hypothalamus and hippocampus following denervation with
      5,7-dihydroxytryptamine (5,7-DHT), ovariectomy (OVX) and gonadal steroid
      manipulation. Seven days after 5,7-DHT injection, 5-HT1a receptor density was
      significantly increased in the ventromedial hypothalamic nucleus (VMN) of intact
      but not OVX female rats. Under these conditions 5-HT1b receptor density was
      unchanged in any brain region examined and 5-HT transporter binding was decreased
      in all 5,7-DHT injected animals. In addition, there was a significant interaction
      between OVX and 5,7-DHT for both the 5-HT1a receptor and the 5-HT transporter in
      the VMN, such that OVX inhibited the 5,7-DHT-induced increase in 5-HT1a receptors
      and attenuated the 5,7-DHT-induced decrease in 5-HT transporter binding. In a
      separate experiment the effect of gonadal steroid manipulation on 5-HT receptor
      binding was assessed. In female OVX rats, 5-HT1a receptor density was unchanged
      by estrogen or estrogen and progesterone administration. In male rats, castration
      significantly decreased 5-HT1a receptor density in the medial preoptic area.
      Estrogen and progesterone administration to female OVX rats increased the density
      of 5-HT1b receptors in the VMN, as compared to estrogen alone. The relationship
      of these results to the role of 5-HT in mediating lordosis behavior is discussed.

PMID- 8159275
TI  - Anterior pituitary estradiol receptors associated with the reinstatement of
      ovulatory cycles after lactation interruption in the rat.
AB  - The participation of adenohypophyseal estradiol receptors in the reinstatement of
      ovulatory cycles after lactation interruption was investigated. In rats whose
      pups were removed on day 13 postpartum (LRX), prolactin levels fell as from 1600
      h on the same day, estradiol peaked on the morning of day 15 and gonadotropins
      and prolactin (PRL) surged on the afternoon of day 15. No significant changes in
      gonadotropins or estradiol levels were observed in rats which remained with their
      litters (LRP); in these rats daily afternoon surges of PRL were detected. No
      significant variations in anterior pituitary nuclear or cytosolic estradiol
      receptors were determined in LRP rats. In the nuclear fraction of LRX rats, an
      important increase (430.8 +/- 124.9%) in receptor titers was observed on day 15.
      In these animals a significant increase (34.8 +/- 1.3%) in cytosolic estradiol
      receptors was observed on day 14, followed by a fall on day 15 (-31.6 +/- 6.6%)
      in comparison to day 13 levels. The receptor variations observed on day 15
      closely resemble estrous cyclic changes determined in adult females. However, an
      observation which does not resemble those cycle variations is the increase in
      cytosolic receptors observed on day 14 in LRX rats. This increase may be the
      consequence of a decrease in dopamine levels induced by pup removal. To our
      knowledge this is the first time that the involvement of pituitary estradiol
      receptors in the reinstatement of ovulatory cycles after lactation interruption
      has been described.

PMID- 8159276
TI  - Effects of exogenous androgen on brain androgen receptors of the fetal rhesus
      monkey.
AB  - Testosterone secreted by the fetal testes masculinizes and defeminizes the
      nonhuman primate brain during a defined prenatal critical period. We previously
      demonstrated the presence of high-affinity, specific androgen receptors (AR) in
      the developing rhesus monkey brain, but did not present data concerning their
      capacity for activation. To achieve this end, we analyzed the AR content in
      brains from intact and gonadectomized rhesus monkey fetuses at approximately 125
      days of gestation, 2 h after injection of either 500 micrograms
      dihydrotestosterone (DHT) or vehicle directly into the fetus. After treatment,
      plasma DHT concentrations increased five-fold in the fetal circulation. In gonad
      intact fetuses, cytosolic AR decreased in preoptic area, medial basal
      hypothalamus, and septum following DHT treatment. No significant effect of DHT
      treatment on nuclear AR was seen. In contrast, the increased level of DHT in the
      maternal circulation decreased cytosolic AR and increased nuclear AR of the
      maternal myometrium. In gonadectomized fetuses, DHT treatment decreased cytosolic
      AR as it did in the intact group. In contrast, a significant increase in nuclear
      AR was seen in preoptic area, medial basal hypothalamus, and tegmentum of these
      fetuses. Thus AR in fetal rhesus brain can be activated by DHT when the gonads
      are removed, but not in the intact fetuses. These data suggest that AR in the
      developing nervous system of rhesus macaques can be activated by exogenous
      androgen and hence are probably functional.

PMID- 8159277
TI  - Opioidergic modulation of N-methyl-D,L-aspartic-acid-stimulated LH release in
      young adult but not older male mice.
AB  - Among the neuromodulators of the GnRH neuronal system are the endogenous opioid
      peptides and the excitatory amino acids. Although the opioid antagonist naloxone
      (NAL) induces LH secretion in many species, there are no reports of an effect of
      NAL on LH release in mice. Our previous studies demonstrated that the excitatory
      amino acid analog N-methyl-D,L-aspartic acid (NMA) stimulates LH release in mice
      and suggested that NMA-induced LH release is mediated via afferents to GnRH
      neurons. In the current study, the role of the endogenous opioid system in the
      regulation of LH release in adult male mice was assessed by testing whether this
      system is a component of the NMA-stimulated LH response. NAL, its quaternary
      derivative NAL methiodide (which remains outside of the blood-brain barrier) and
      saline (SAL) were administered alone and in combination with NMA via intravenous
      catheters. Although neither opioid antagonist stimulated LH release when
      administered alone, each significantly potentiated the LH response to NMA in
      young adult (10- to 14-week-old) male mice (p < 0.01) but not in older (10- to 16
      month-old) male mice. The equivalent action of the two ipioid blockers suggested
      an action outside of the blood-brain barrier. To determine whether opioid
      blockade altered pituitary sensitivity to GnRH, a dose response for exogenously
      administered GnRH was first determined, and low and high doses of GnRH were
      tested in combination with NAL or SAL. Neither treatment was effective in
      altering the LH response to GnRH, indicating that the action of the opioid
      antagonists was at a suprapituitary location. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159278
TI  - In vivo alterations in the gonadotropin-releasing hormone pulse generator and the
      secretion and clearance of luteinizing hormone in the uremic castrate rat.
AB  - To investigate the mechanisms subserving the reported alterations in the
      pulsatile release of LH in uremia, we simultaneously studied endogenous
      accumulation of GnRH in the pituitary gland and the secretion and clearance of LH
      in vivo in experimentally uremic, orchidectomized rats. The temporal pattern of
      GnRH secretion was assessed by intrapituitary microdialysis, the dynamics of
      plasma LH by continuous exchange transfusion. Studies were performed in rats
      rendered uremic by subtotal nephrectomy (n = 8) and control rats which were
      either fed ad libitum (n = 8) or pair-fed with the uremic animals (n = 8). Blood
      samples were obtained at 5-min and microdialysate samples at 10-min intervals
      over a period of 270 min. The pulsatile secretory characteristics of GnRH and LH
      and the half-life of plasma LH were estimated by multiple-parameter deconvolution
      analysis. The temporal relationship between the hormone concentrations and
      between the secretory events of GnRH and LH was assessed by cross-correlation
      analysis and hypergeometric coincidence analysis. We observed that: (1) the
      estimated half-life of plasma LH was prolonged in uremic (59 +/- 10 min) rats
      compared to ad libitum-fed (17 +/- 3 min, p = 0.014) and pair-fed controls (19 +/
      3 min, p = 0.025); (2) the LH production rate was decreased in uremic animals
      (18 +/- 5 ng/ml.270 min) compared to ad libitum-fed (37 +/- 4 ng/ml.270 min, p =
      0.002) and pair-fed controls (48 +/- 9 ng/ml.270 min, p = 0.0006); (3) the
      reduction of LH secretion rate in the uremic animals was accounted for by a
      decrease in detectable LH pulse frequency (2.1 +/- 0.2 peaks/h) compared to ad
      libitum-fed (3.1 +/- 0.1 peaks/h, p = 0.01) and pair-fed controls (2.8 +/- 0.2
      peaks/h, p = 0.06) and a diminished mass of hormone released per burst (uremic
      1.8 +/- 0.2 ng/ml, ad libitum-fed 2.6 +/- 0.3 ng/ml, p = 0.05, pair-fed 3.8 +/-
      0.8 ng/ml, p = 0.025); (4) the secretion rate of GnRH was reduced to a similar
      degree in uremic rats (180 +/- 15 pg/tube.270 min, p = 0.04) and pair-fed
      controls (170 +/- 26 pg/tube.270 min, p = 0.04) compared to ad libitum-fed
      controls (270 +/- 36 pg/tube.270 min). In contrast to the reduced number of
      detectable LH secretory events, the frequency of GnRH secretory peaks in uremic
      rats was not different from ad libitum-fed and pair-fed controls.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8159280
TI  - Current bibliographies of neuropeptides prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8159279
TI  - GABA has excitatory actions on GnRH-secreting immortalized hypothalamic (GT1-7)
      neurons.
AB  - The effects of gamma-aminobutyric acid (GABA) on clonal gonadotropin-releasing
      hormone (GnRH)-secreting hypothalamic (GT1-7) neurons were investigated using
      patch-clamp and fura-2 imaging techniques. Local application of GABA (100 microM)
      to GT1-7 cells voltage-clamped in the whole-cell configuration immediately
      increased membrane conductance and noise consistent with activation of the GABAA
      receptor-Cl- channel complex. Depolarization activated transient Na+ currents
      which were abolished by tetrodotoxin (TTX; 0.5 microM), and more sustained Ca2+
      currents. Under constant current conditions, GT1-7 cells fired spontaneous action
      potentials, and depending on the Cl- equilibrium potential, GABA either
      depolarized cells, causing a rapid activation of action potentials, or
      hyperpolarized cells. In order to determine the effect of GABA on intact cells,
      the cell-attached patch configuration was used to record extracellularly. Under
      these conditions, application of GABA (100 microM), but not the GABAB receptor
      agonist baclofen (10 microM), immediately evoked multiple action potentials.
      Measurement of [Ca2+]i using fluorescence video microscopy and fura-2 revealed
      spontaneous, transient, repetitive increases in [Ca2+]i which had a periodicity
      ranging from 1 to 60 s. These Ca2+ oscillations were abolished by TTX (1 microM)
      and by the removal of extracellular Ca2+. Application of GABA (1 and 10 microM)
      induced an immediate increase in [Ca2+]i in all cells and increased the frequency
      of Ca2+ oscillations in a dose-dependent manner. The GABA-induced increase in
      [Ca2+]i was abolished by bicuculline and by the removal of extracellular Ca2+,
      and was inhibited by TTX. Baclofen (1 microM) had no effect on [Ca2+]i. These
      results suggest that activation of GABAA receptors has an excitatory action on
      GnRH-secreting immortalized hypothalamic neurons caused by a Cl(-)-dependent
      depolarization. GABA has been reported to increase GnRH secretion; a direct
      stimulatory action of the neurotransmitter on GABAA receptors of GnRH-secreting
      hypothalamic neurons may be responsible for this effect.

PMID- 8159281
TI  - Inhibition in the release of immunoreactive beta-endorphin from the
      periaqueductal grey during isometric contractions of cat hind-limb muscles: the
      effects of clonidine.
AB  - Glass microelectrodes, coated with antibodies specific for beta-endorphin, were
      inserted into the right periaqueductal grey (PAG) (at PO.5-1.0 mm, LR 2.0 mm and
      6.0 mm below the dorsal surface of the colliculi) of cats anesthetized with alpha
      chloralose to determine whether immunoreactive beta-endorphins (ir-END) were
      released in response to fatiguing isometric contractions of the hind-limb
      muscles. Probes were inserted into the PAG prior to, during and following muscle
      contraction in the absence or presence of clonidine. ir-END was released from the
      PAG up to 3 h after surgery was completed while cats remained at rest. In the
      absence of clonidine, mean arterial pressure increased by 65 +/- 12 mmHg during
      contractions and the release of ir-END was inhibited during the contraction
      periods compared to resting periods. Clonidine abolished the pressor response to
      muscular contraction when injected into the PAG, but did not cause the release of
      ir-END during fatiguing isometric contractions. These data suggest that isometric
      contractions of skeletal muscle do not induce the release of ir-END-like
      substances from the PAG and clonidine does not attenuate the muscle pressor
      response by causing the release of ir-END from this level in the PAG.

PMID- 8159282
TI  - Comparison of the NPY receptors mediating vasoconstriction of the guinea-pig
      uterine artery and thoracic vena cava using a range of NPY analogues.
AB  - The ability of analogues of neuropeptide Y (NPY) to produce direct
      vasoconstriction, or to antagonize NPY constrictions, was examined in isolated
      segments of the thoracic vena cava and the uterine artery of guinea-pigs, where
      NPY mediates a slow phase of sympathetic vasoconstriction. [Leu31,Pro34]NPY,
      NPY(13-36) and NPY(18-36) all contracted the uterine artery and the vena cava.
      Contractions produced by [Leu31,Pro34]NPY were similar in time course to those
      produced by porcine NPY (pNPY), although contractions produced by NPY(13-36) or
      NPY(18-36) typically were slower than pNPY contractions. In both vessels the
      order of potency of the agonists was pNPY > or = [Leu31,Pro34]NPY > NPY(13-36) >
      NPY(18-36). High concentrations (10(-5)mol.l-1) of pNPY or [Leu31,Pro34]NPY
      produced desensitization of contractions of the uterine artery produced by NPY(13
      36). The reported NPY receptor antagonists, PYX-1 and PYX-2 (5 x 10(-6)mol.l-1),
      slightly reduced (by 21-47%) the magnitude of constrictions produced by exogenous
      pNPY (1-3 x 10(-8) mol.l-1) in both the uterine artery and the vena cava. These
      results show that the NPY receptors mediating slow sympathetic vasoconstriction
      of both the uterine artery and the vena cava are likely to be predominantly Y1
      receptors, despite differences between the adrenoceptors mediating sympathetic
      responses in the two blood vessels.

PMID- 8159283
TI  - Capsaicin-like effect of resiniferatoxin in the rat stomach.
AB  - Neurochemical and functional studies were performed to investigate and to compare
      the effects of resiniferatoxin and capsaicin in the rat stomach. Neonatal
      administration of resiniferatoxin (0.6-1.6 mumol/kg subcutaneously (s.c.))
      produced a marked decrease in gastric calcitonin gene-related peptide-like
      immunoreactivity in both secretory and non-secretory region of the stomach.
      Almost complete depletion of the peptide was determined by neonatal
      administration of capsaicin (164 mumol/kg s.c.). Vasoactive intestinal
      polypeptide-like immunoreactivity was concomitantly unaffected by resiniferatoxin
      or capsaicin, thus showing the selectivity of action of the neurotoxins on
      gastric afferent fibers. Oral administration of an equimolar dose (0.3 nmol/kg)
      of resiniferatoxin or capsaicin together with 50% ethanol reduced at a similar
      extent gastric haemorrhagic lesions produced by the mucosal barrier-breaker
      agent. These findings provide evidence that resiniferatoxin and capsaicin may act
      on a common neuronal target in the rat stomach and that the acute exciting
      (protective) effect is of the same magnitude.

PMID- 8159284
TI  - The role of central corticoliberin in the ether stress-induced secretion of
      neurohypophyseal hormones and corticosterone in the rat.
AB  - As corticotropin-releasing factor (CRF) and oxytocin (OXT) are released in
      response to various stressors and a role of CRF in stress-induced OXT secretion
      has been proposed by previous authors, the present experiments were scheduled to
      investigate the participation of the brain CRF system in the stress-evoked
      release of OXT, arginine-8-vasopressin (AVP) and corticosterone. CRF-antiserum
      (AS) was given into the lateral ventricle of the brain of Wistar male rats, and
      24 h later, the injection was repeated 30 min prior to ether stress followed by
      decapitation in 5 min. Plasma OXT and AVP were measured by radioimmunoassay and
      corticosterone by fluorimetry. Ether stress increased the levels of
      corticosterone and OXT, but not that of AVP. CRF-AS alone did not change the
      secretion of these hormones. CRF-AS pretreatment blocked the corticosterone
      releasing action of ether stress, whereas it exerted no influence on the stress
      induced OXT secretion into the circulation. There was no effect of a combined
      application of CRF-AS and stress on the plasma AVP level. These results suggest
      that the central CRF system is involved in the ether stress-elicited
      corticosterone response, however CRF is unlikely to be connected with the
      regulation of OXT secretion under these experimental conditions.

PMID- 8159285
TI  - Subdiaphragmatic vagotomy does not prevent the anti-exploratory effect of
      caerulein in the elevated plus-maze.
AB  - We compared the action of subdiaphragmatic vagotomy upon the anti-exploratory and
      motor depressant effects of caerulein, an agonist of cholecystokinin (CCK)
      receptors, in male rats. Vagotomized rats entered more frequently into the open
      arms of elevated plus-maze compared to intact control rats. Caerulein (1
      microgram/kg subcutaneously (s.c.)) significantly suppressed the exploratory
      behaviour in vagotomized rats but not in intact and sham-operated rats. In
      contrast, subdiaphragmatic vagotomy did not change the locomotor activity of rats
      in open field compared to intact and sham-operated animals. At a higher dose (10
      micrograms/kg s.c.), the caerulein pretreatment markedly decreased the number of
      line crossings, rearings and head-dippings of intact animals in open field. In
      sham-operated rats caerulein also suppressed the locomotor activity, whereas in
      vagotomized rats it only tended to reduce the frequency of rearings.
      Consequently, the present study revealed the different action of vagotomy upon
      the motor depressant and anti-exploratory effects of caerulein. These results
      support the view that CCKA receptors in the gastrointestinal tract are mediating
      the motor depressant, whereas CCKB receptors in the brainstem are involved into
      the mediation of anti-exploratory effect of caerulein.

PMID- 8159287
TI  - Stimulation of locomotion in neonate rats by TRH analogue CG3703.
AB  - Thyrotropin releasing hormone (TRH) and its analogues have been shown to
      depolarise motoneurons and stimulate cyclical motor activities such as
      respiration and locomotion. It has been suggested that one of its roles might be
      modulation of neuronal membrane excitability to release intrinsic rhythmicity.
      The present experiments were designed to determine whether it would initiate
      locomotion in the neonate rat prior to the development of spontaneous walking. It
      was found that the TRH analogue CG3703 did activate locomotion in 3-day-old rat
      pups. Quantification of various gait parameters and study of spatiotemporal
      footfall patterns showed the gait to be indistinguishable from the spontaneous
      locomotion of older pups. Possible loci of action are discussed.

PMID- 8159286
TI  - Effects of neuromedin U (NMU)-8 on the rat hypothalamo-pituitary-adrenal axis.
      Evidence of a direct effect of NMU-8 on the adrenal gland.
AB  - A 6-day subcutaneous (s.c.) treatment of adult rats with NMU-8 (1.5 or 6
      micrograms/100 g/day) increased the average volume of zona fasciculata cells and
      decreased the number of zona reticularis cells in the adrenal cortex. The lower
      dose of NMU-8 did not change blood ACTH concentration and adrenal weight, but it
      notably enhanced serum corticosterone level and basal corticosterone output by
      adrenal slices. ACTH blood level increased after ether stress in both control and
      NMU-8-treated rats, but stress-evoked rise in serum corticosterone was observed
      only in control rats. The higher dose of NMU-8 increased the level of circulating
      ACTH; however, it decreased adrenal weight and had no effect on serum
      corticosterone concentration and basal corticosterone output by adrenal slices.
      NMU-8 (10(-10)/10(-6) M) did not affect basal and ACTH-stimulated corticosterone
      yield by isolated adrenocortical cells, nor did it change their cytosolic Ca2+
      concentration. NMU-8 (10(-8) M) markedly raised basal corticosterone secretion by
      adrenal slices (including cortex and medulla); higher concentrations of NMU-8
      (10(-7)/10(-6) M) were ineffective on basal corticosterone secretion, but
      strongly inhibited the response to ACTH stimulation. On the ground of these
      findings it seems reasonable to suggest that NMU-8 exerts a biphasic effect on
      the function of the peripheral branch of the hypothalamo-pituitary-adrenal axis
      in rats: NMU-8 at low doses directly stimulates the function and growth of the
      adrenal cortex, while at high doses exerts a direct inhibitory action.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8159288
TI  - The enigma of olfactory learning revisited.
AB  - If, as indicated in olfactory conditioning studies, rats are able to demonstrate
      primate-like behavior by their acquisition of response strategies, rodent
      olfactory learning may provide a particularly useful model for neurobiological
      analyses of learning and memory. Reid and Morris [Proc. R. Soc. Lond., Ser. B
      247, 137-143 (1992); Trends Neurosci. 16, 17-20 (1993)] have recently challenged
      these views. They suggested that the evidence for acquisition of an olfactory
      learning set in rodents is insufficient and that rat olfactory learning may
      provide no special advantage for the neurobiologist. This essay reviews the
      relevant studies and concludes that there are serious shortcomings in the Reid
      and Morris argument, that the available data base provides clear evidence for the
      claim that rats acquire abstract rules for responding and that olfactory learning
      may be qualitatively different from other forms of instrumental learning in
      rodents.

PMID- 8159289
TI  - Sub-millisecond coincidence detection in active dendritic trees.
AB  - Stimulations of a morphologically reconstructed cortical pyramidal cell suggest
      that the long, thin, distal dendrites of such a cell may be ideally suited for
      nonlinear coincidence-detection at time-scales much faster than the membrane time
      constant. In the presence of dendritic sodium spiking conductances, such
      hypothetical computations might occur by two distinct mechanisms. In one
      mechanism, fast excitatory synaptic currents inside a thin dendrite create strong
      local depolarizations, whose repolarization--resulting from charge equalization-
      can be 100-fold faster than the membrane time-constant; two such potentials in
      exact coincidence might initiate a dendritic spike. In the alternate mechanism,
      dendritic sodium spikes which do not fire the soma nonetheless create somatic
      voltage pulses of millisecond width and a few millivolts amplitude. The soma may
      fire upon the exact coincidence of several of these dendritic spikes, while their
      strong delayed-rectifier currents prevent the soma from temporally summating
      them. The average firing rate of a compartmental simulation of this reconstructed
      cell can be highly sensitive to the precise (submillisecond) arrangement of its
      inputs; in one simulation, a subtle reorganization of the temporal and spatial
      distribution of synaptic events can determine whether the cell fires continuously
      at 200 Hz or not at all. The two cellular properties postulated to create this
      behavior--fast, strong synaptic currents and spiking conductances in the distal
      dendrites--are at least consistent with physiological recordings of somatic
      potentials from single and coincident synaptic events; further measurements are
      proposed. The amplitudes and decays of these simulated fast EPSPs and dendritic
      spikes can be quantitatively predicted by approximations based on dendritic
      properties, intracellular resistance, and transmembrane conductance, without
      invoking any free parameters. These expressions both illustrate the dominant
      biophysical mechanisms of these very transient events and also allow
      extrapolation of the simulation results to nearby parameter ranges without
      requiring further simulation. The possibility that cortical cells perform
      temporally precise computations on single spikes touches many issues in cortical
      processing: computational speed, spiking variability, population coding, pairwise
      cell correlations, multiplexed information transmission, and the functional role
      of the dendritic tree.

PMID- 8159290
TI  - Development of the suprachiasmatic nucleus in rats during ontogenesis: serotonin
      immunopositive fibers.
AB  - The innervation of the suprachiasmatic nucleus by serotoninergic fibers has been
      studied in rats from the 22nd embryonic until the 21st postnatal day. The
      serotoninergic fibers were detected with the pre-embedding immunocytochemical
      technique at the electron-microscopic level using antibodies to serotonin.
      Serotonin-immunopositive fibers were always identified as axons as they contained
      numerous synaptic vesicles both in fetuses and postnatal rats. Moreover,
      immunopositive dense core vesicles appeared in the axons after birth. From the
      end of fetal life onwards, the serotonin-immunopositive axons made specialized
      contacts with the immunonegative neurons, mainly with their dendrites and to a
      lesser extent with cell bodies and axons. In fetuses, only immature synapses
      (presynapses) were observed. After birth, presynapses were replaced by typical
      synapses with the thickened pre- and postsynaptic membranes, accumulations of
      dense materials at the pre- and postsynaptic membranes as well as with an
      accumulation of synaptic vesicles at the presynaptic membrane. The functional
      significance of the serotoninergic input to the suprachiasmatic nucleus in
      ontogenesis is discussed.

PMID- 8159291
TI  - The mouse 5-hydroxytryptamine1B receptor is localized predominantly on axon
      terminals.
AB  - The 5-hydroxytryptamine1B receptor is a serotonin receptor subtype which is
      expressed predominantly in the basal ganglia. It has been suggested to play a
      role in movement and appetite control as well as in certain pathological states
      such as migraine. The recent cloning of the 5-hydroxytryptamine1B gene as well as
      the discovery of a radioligand that labels in rodents 5-hydroxytryptamine1B and
      possibly 5-hydroxytryptamine1D alpha receptors (S-CM-G[125I]TNH2) allowed us to
      compare the distribution of the messenger RNA and of the protein in mouse brain
      sections. A high 5-hydroxytryptamine1B messenger RNA level is found in the
      caudate-putamen in medium spiny neurons that project to the globus pallidus and
      the substantia nigra. In contrast, no messenger RNA is expressed in the globus
      pallidus and substantia nigra although these structures reveal the highest level
      of 5-hydroxytryptamine1B binding sites. In the hippocampus, 5-hydroxytryptamine1B
      messenger RNA is localized in the cell bodies of pyramidal cells of the CA1 field
      while the protein is found predominantly in the dorsal subiculum, a projection
      zone for the CA1 pyramidal neurons. In the cerebellum, 5-hydroxytryptamine1B
      messenger RNA is expressed in the Purkinje cells, which display no receptor
      binding sites. Conversely, moderate binding is found in the deep nuclei of the
      cerebellum, the main projection zone of the Purkinje cells. 5-Hydroxytryptamine1B
      sites are also detected in the superficial gray layer of the superior colliculus
      and the lateral geniculate nucleus, brain regions containing the terminals of
      retinal ganglion cells. The soma of these ganglion cells express high levels of 5
      hydroxytryptamine1B messenger RNA while no 5-hydroxytryptamine1B binding sites
      were found in the retina. This study demonstrates that the main brain regions,
      expressing 5-hydroxytrypamine1B messenger RNA contain low densities of 5
      hydroxytryptamine1B binding sites. Conversely, the major projection areas of
      these anatomical structures do not express detectable levels of 5
      hydroxytryptamine1B messenger RNA, but present a high density of binding sites.
      In addition, our data suggest that the distribution of the 5-hydroxytryptamine1D
      alpha binding sites is different from that of the 5-hydroxytryptamine1D alpha
      messenger RNA. These results together with previous lesion studies, indicate that
      the 5-hydroxytryptamine1B and possibly the 5-hydroxytryptamine1D alpha receptors
      are localized predominantly on axon terminals, while their expression is low or
      absent at the somatodendritic level. The 5-hydroxytryptamine1D alpha proteins
      might therefore contain an addressing signal allowing their transport toward
      nerve endings.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8159292
TI  - Islands and striosomes in the neostriatum of the rhesus monkey: non-equivalent
      compartments.
AB  - Cytoarchitectonically defined cell-dense islands and regions of low
      acetylcholinesterase reactivity referred to as striosomes have been regarded as
      equivalent markers of the non-matrix compartment in the neostriatum. We examined
      islands and striosomes in adjacent sections to determine the degree of
      correspondence between the two neostriatal compartmental markers. Islands are
      aggregated centrally within the caudate, whereas striosomes are located
      throughout the entire nucleus, including the dorsolateral and ventromedial
      sectors. Moreover, even within the central sector, striosomes are more prevalent
      than islands. The present quantitative analysis suggests that islands may be
      further characterized as acetylcholinesterase-poor since the vast majority of
      islands co-localize with striosomes. However, due to the fact that striosomes are
      more numerous and more widely distributed throughout the neostriatum, less than a
      third of all striosomes are coincident with islands in adjacent sections.
      Comparison of each of these compartmental markers with the patterned terminal
      field of the prefrontal cortical projection revealed a near one-to-one
      correspondence between islands and terminal-free zones in the prefrontal
      projection. The percentage of striosomes which are aligned with fenestrations in
      the prefrontal projection is also quite high; however, because more striosomes
      than islands are found within the prefrontal terminal domain, some striosomes
      that fit within terminal-free zones do not have corresponding islands. These
      results indicate that islands and striosomes are not entirely equivalent
      compartmental markers and further suggest that contemporary, two-compartment
      models may not adequately represent the heterogeneity of the neostriatum.

PMID- 8159293
TI  - Differential contribution of motor cortex and caudate nucleus to instrumental
      tongue-forelimb synchronization in rats: a functional ablation study.
AB  - The functional ablation technique was used to assess the role of motor cortex and
      caudate nucleus in a complex skilled movement. Rats were trained to synchronize
      tongue and forepaw movements in a drinking box equipped with a retractable spout
      which was automatically withdrawn after every lick but could be returned by
      pressing and releasing a lever placed 4 cm below the spout. The animals learned
      to perform short presses synchronized with the lick cycle in such a way as to
      allow continuous drinking. Neural circuits implementing these lick-associated
      instrumental movements were blocked by intracranial injection of 10 ng of
      tetrodotoxin. Bilateral blockade of the motor cortex interfered with lick
      synchronized bar pressing, but did not significantly influence licking from a
      stationary spout. Both licking and bar-pressing were impaired by bilateral
      injection of tetrodotoxin into the lateral part of the caudate nucleus for the
      duration of the tetrodotoxin-induced inactivation of the target region. The
      instrumental tongue-forelimb synchronization recovered considerably later, i.e.
      after two to three days. Functional blockade of the medial part of the caudate
      nucleus caused only a partial impairment of lick-synchronized bar pressing
      lasting less than 7 h and did not significantly influence consummatory licking.
      It is concluded that the tongue-forepaw synchronization is disrupted by blockade
      of motor cortex or lateral caudate considerably longer than the performance of
      the isolated component movements.

PMID- 8159294
TI  - Effect of dopamine and baclofen on N-methyl-D-aspartate-induced burst firing in
      rat ventral tegmental neurons.
AB  - Intracellular microelectrode recordings were made from dopamine-containing
      neurons of the ventral tegmental area or substantia nigra zona compacta in rat
      brain slices in vitro. The firing pattern of the neurons was switched from a
      tonic, single-spike pattern to a burst firing mode by adding N-methyl-D-aspartate
      (20 microM) to the superfusing solution; after adding tetrodotoxin the membrane
      potential underwent rhythmical oscillations of 20-40 mV at 0.5-2 Hz. Baclofen (1
      microM) and dopamine (30 microM) hyperpolarized the neurons; when the potential
      was restored to its original level, the oscillations of potential and/or burst
      firing were not observed, but the tonic firing pattern was restored. These
      effects of baclofen and dopamine were prevented by barium (1 mM), which also
      prevented the membrane hyperpolarization. Oscillations of membrane current of a
      similar frequency were observed when the somatic membrane was voltage-clamped at 
      60 mV; these were also blocked by barium (1 mM). It is concluded that the
      oscillations in membrane potential observed with N-methyl-D-aspartate are
      generated predominantly at a dendritic location which is not voltage-clamped with
      an electrode at the soma. Baclofen and dopamine inhibit the oscillations by
      increasing the potassium conductance and hyperpolarizing the dendrites.

PMID- 8159295
TI  - Ultrastructural changes in gonadotropin-releasing hormone neurons as a function
      of age and ovariectomy in rats.
AB  - In this study we examined the effects of aging on various aspects of the
      ultrastructure of gonadotropin-releasing hormone neurons in female rats,
      including the density of synaptic input and the volume fraction of various
      subcellular organelles. In addition, we explored the possibility that removal of
      estrogen might provide a protective effect on the aging of the gonadotropin
      releasing hormone neuron as exposure to gonadal steroids alters the time course
      of reproductive aging. Our experimental groups included four- and 18-20-month-old
      virgin female rats divided as follows: young intact, young short-term
      ovariectomized, old intact, old short-term ovariectomized and old long-term
      ovariectomized. Brain tissue was processed for immunocytochemical detection of
      gonadotropin-releasing hormone neurons and selected cells from the preoptic area
      were chosen for electron microscopic examination. The percentage of plasma
      membrane containing synaptic modification was quantified using a morphometrics
      program, and the volume fraction of lysosomes/lipofuscin, rough endoplasmic
      reticulum and Golgi apparatus were estimated using point count stereology.
      Whereas we had previously found a significant increase in the density of synaptic
      input to gonadotropin-releasing hormone neurons in aged virgin male rats, the
      density of synaptic input to gonadotropin-releasing hormone cells in the virgin
      female was not affected by age. The volume fraction of lysosomes/lipofuscin was
      increased in all age groups. Aging produced a dramatic decrease in the volume
      fraction of rough endoplasmic reticulum as well as a decrease in Golgi,
      suggesting a general decrease in biosynthetic activity of the cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8159296
TI  - Analysis of synchrony (correlations) in neural populations by means of unit-to
      aggregate coherence computations.
AB  - This paper presents a general outline of the mathematical basis of an approach
      for analysis of population synchrony by means of coherence computations, a
      demonstration of the use of this approach, and a discussion of the potential
      utility and limitations of the approach. The coherence function for the pair
      single-unit activity and population-aggregate activity is studied in the light of
      theoretical considerations on the superposition of partially correlated unitary
      activities. The theoretical analysis, as well as computer simulations, indicate
      that when a subset of units in a population are correlated around some frequency,
      the unit-to-aggregate coherence function for members of this subset shows, in a
      wide range of conditions, a clear peak around that frequency (and possibly
      harmonic peaks), being very low at other frequencies where there is no synchrony.
      Specifically, the value of the peak coherence at the frequency of synchrony
      reflects the strength of the unitary correlations and their extent within the
      population, the numerical size of the population, and the degree of phase
      concentration for the units of the correlated subset. This value remains
      substantial, or at least significant, for wide ranges of values of these
      parameters. In contrast, the unit-to-aggregate coherence function for the
      remaining uncorrelated units has very low values at all frequencies, and tends to
      zero in the case of a large population. On the basis of these properties, an
      approach is presented for analysis of synchrony (correlations) in a neural
      population, which is simple and efficient, particularly when the population is
      large in numerical size. This approach utilizes unit-to-aggregate coherence
      computations for a sample of recorded unitary activities as a means for detecting
      population synchrony and estimating the extent of synchrony. In addition, this
      analysis can provide useful information on other characteristics of synchrony,
      such as the strengths of the unitary correlations. The use of the approach is
      demonstrated with an example from a study of fast rhythms in inspiratory
      activities, and other applications are also briefly described. The main advantage
      of unit-to-aggregate coherence analysis is that by using readily recorded
      activities, it efficiently identifies correlated units in a population and
      provides information on characteristics of synchrony, at every frequency within
      the range of interest.

PMID- 8159297
TI  - The kidney as a determinant of hypertension.

PMID- 8159298
TI  - Cytokines in the progression of renal disease.

PMID- 8159299
TI  - Idiopathic membranous nephropathy in the elderly.
AB  - In this retrospective non-randomized study we reviewed the outcome for 41
      patients with membranous nephropathy older than 65 years at onset and followed
      for at least 1 year. Twelve of the patients never received any specific treatment
      (group A), 15 were treated with a 6-month course of methylprednisolone alternated
      to chlorambucil every other month (group B), and 14 received corticosteroids
      alone for 3-12 months (group C). At the end of a mean follow-up of 92 +/- 61
      months in group A, 53 +/- 35 in group B, and 38 +/- 25 in group C there were
      significantly more remissions of nephrotic syndrome in group B than in group A (P
      = 0.035) or in group C (P = 0.010). Moreover patients in group B spent a
      significantly longer period without nephrotic syndrome than patients in group A
      (P = 0.000) and C (P = 0.000). Three patients in group A and one in group B died.
      During the follow-up six patients of group A, two of group B, and five of group C
      developed renal function deterioration. In patients followed for at least 5 years
      the mean plasma creatinine increased from a basal of 112 +/- 29 to 239 +/- 287
      mumol/l at the 5th year in group A and from 113 +/- 14 to 124 +/- 30 mumol/l in
      group B. The mean urine protein excretion remained unchanged in group A (basal
      4.6 +/- 2.3 versus 4.8 +/- 5.7 g/day at 5 years) while it decreased in group B
      (from a basal of 6.8 +/- 3.5 to 1.1 +/- 0.4 g/day at 5 years).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8159300
TI  - Cyclosporin versus cyclophosphamide for patients with steroid-dependent and
      frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized
      controlled trial.
AB  - OBJECTIVE: To compare the efficacy (maintenance of remission), safety and
      tolerability of cyclosporin (CsA) with those of cyclophosphamide in patients with
      steroid-dependent or frequently relapsing nephrotic syndrome (NS). DESIGN: Open,
      prospective, randomized, multicentre, controlled study for parallel groups,
      stratified for adults and children. The setting was in nephrological departments
      in Italy. SUBJECTS AND INTERVENTIONS: Seventy-three patients with steroid
      sensitive idiopathic NS admitted to the study were randomly assigned to
      cyclophosphamide (2.5 mg/kg/day) for 8 weeks or CsA (5 mg/kg/day in adults, 6
      mg/kg/day in children) for 9 months, tapered off by 25% every month until
      complete discontinuation at month 12. Seven patients lost to follow up were not
      considered in the analysis. The remaining 66 patients were followed up for 3-24
      months after randomization. MAIN OUTCOME MEASURES: Relapse-free survival; number
      of N.S. relapses/patient/year; cumulative dose of prednisone/patient; laboratory
      investigations (kidney and liver functions, haematological parameters); incidence
      of adverse events. RESULTS: At month 9, 26 of 35 CsA-treated patients were still
      in complete remission and a further five patients were in partial remission; 18
      of 28 cyclophosphamide-treated patients were in complete remission, and one in
      partial remission (P = NS). No difference between adults and children was seen
      with either treatment. The risk of relapse was similar between frequent relapsers
      (19 of 22) and steroid-dependent patients (8 of 14) given CsA, and those given
      cyclophosphamide (5 of 15 and 6 of 15). The mean number of relapses per year and
      the mean dose of prednisone per year were significantly less (P < 0.001) in both
      groups for the experimental year than for the year before randomization. At 2
      years, 25% of the patients given CsA (50% adults and 20% children) and 63% of
      those given cyclophosphamide (40% adults and 68% children) had not had any
      relapse of NS. Tolerance to the two drugs was generally good. The CsA-related
      side-effects were mild and disappeared after drug discontinuation. CONCLUSIONS:
      This study shows that both treatments are effective and well tolerated; more
      patients given cyclophosphamide had stable remissions.

PMID- 8159301
TI  - Thresholds of serum calcium oxalate supersaturation in relation to renal function
      in patients with or without primary hyperoxaluria.
AB  - Systemic oxalosis is a constant feature in patients with primary hyperoxaluria
      type 1 (PH1) and chronic renal failure (CRF) and is not prevented by regular
      dialysis (RDT), because removal cannot keep up with retention and overproduction
      of oxalate. These patients are candidates to kidney and/or liver transplantation,
      which should be ideally planned prior to the development of oxalosis. However,
      methods to detect the presence and extent of oxalosis are invasive and poorly
      reproducible, and only indirect approaches are feasible. Because supersaturation
      of body fluids is an essential condition for oxalotic deposits to form, we have
      assessed serum calcium oxalate saturation (beta CaOx) in 12 patients with PH1 and
      26 with PH1-unrelated renal diseases and varying degrees of CRF. Nineteen healthy
      individuals were taken as controls. beta CaOx was closely dependent on oxalate
      serum levels. Serum oxalate and beta CaOx were increased in patients with CRF as
      compared to controls, and were inversely related to GFR, assessed as creatinine
      clearance. However, at any level of GFR, both were always greater in PH1
      patients. From the slopes of the regression of beta CaOx over ClCr, saturation
      was predicted to be obtained at ClCr ranging 24-34 and 8-11 ml/min/1.73 m2 in PH1
      and non-PH1 patients respectively. Based on the dependence of beta CaOx on
      oxalate, saturation was associated with serum oxalate between 44 and 46 mumol/l,
      irrespective of either the prevailing GFR or the underlying disease. These simple
      procedures represent a valuable non-invasive tool to define the risk of systemic
      oxalosis and may assist in timing of transplantation.

PMID- 8159302
TI  - Effects of delayed treatment with enalapril and/or lovastatin on the progression
      of glomerulosclerosis in 5/6 nephrectomized rats.
AB  - To evaluate the effect of delayed treatment with enalapril or lovastatin on the
      progression of glomerulosclerosis and to examine if the combined treatment with
      enalapril and lovastatin show synergistic effect, a total of 31 Sprague-Dawley
      rats were studied for 16 weeks following 5/6 nephrectomy (NPX). Treatment was
      delayed until 8 weeks after NPX. In untreated control rats (n = 8), sustained
      systemic hypertension with increasing proteinuria, serum cholesterol,
      triglyceride, BUN and widespread glomerulosclerosis and mesangial expansion were
      observed. Treatment with enalapril alone (R, n = 8) reversed systemic
      hypertension, prevented a further increase in proteinuria, and significantly
      reduced glomerulosclerosis relative to the control group. Treatment with
      lovastatin alone (L, n = 7) also reduced glomerulosclerosis and serum cholesterol
      compared to the controls. The drug also prevented a further increase in
      proteinuria and systemic blood pressure although the difference from the control
      rats did not reach statistical significance. Treatment with both enalapril and
      lovastatin (RL, n = 8) almost completely prevented glomerulosclerosis and
      significantly reduced mesangial expansion, systemic blood pressure, serum
      cholesterol, and proteinuria compared to controls. Only the combined treatment
      stabilized BUN and reduced mesangial expansion compared to control R, or L
      groups. Conclusion. Delayed treatment with enalapril or lovastatin is effective
      in preventing the progression of glomerulosclerosis, and combined treatment
      appears to show synergistic effect in 5/6 nephrectomized rat model.

PMID- 8159303
TI  - Hypothyroidism retards progressive glomerulosclerosis in the rat by a reduction
      in food intake.
AB  - Hypothyroidism diminishes proteinuria and prolongs survival in several immune
      models of progressive renal failure. In the well-characterized non-immune model
      of 5/6 nephrectomy we studied the effects of thyroidectomy (Tx) on the
      development of proteinuria and glomerulosclerosis (GS). Hypothyroidism was
      confirmed by lower values of thyroxine in Tx rats compared to sham Tx rats at 9
      weeks (12.6 +/- 6.7 nmol/l Tx versus 37.7 +/- 10.8 nmol/l sham Tx) and 12 weeks
      after operation (7.2 +/- 4.9 nmol/l Tx versus 14.4 +/- 4.1 nmol/l sham Tx). Tx
      resulted in a reduction in mean arterial blood pressure and proteinuria and a
      lower incidence of GS (4.2 +/- 3.1% Tx versus 17.1 +/- 10.0% sham Tx) 12 weeks
      after nephrectomy, along with a decrease in food intake (104 +/- 13 g/week Tx
      versus 138 +/- 10 g/week sham Tx). In the same experiment a third group of sham
      Tx rats was pair fed to the Tx rats, resulting in values similar to those of Tx
      rats for proteinuria and the incidence of GS (6.0 +/- 4.9% pair fed sham Tx).
      Thyroxine levels at 9 and 12 weeks were comparable to those in sham Tx rats fed
      ad libitum. No association was found between the incidence of GS and glomerular
      volume. Studies of the inulin clearance in a second set of experiments showed
      that glomerular filtration rate and renal plasma flow are lower in hypothyroid
      rats compared to sham Tx rats. We conclude that hypothyroidism has a renal
      protective effect due to a decrease in food intake resulting in alterations in
      renal haemodynamics.

PMID- 8159304
TI  - Long-term efficiency, biocompatibility, and clinical safety of combined
      simultaneous LDL-apheresis and haemodialysis in patients with
      hypercholesterolaemia and end-stage renal failure.
AB  - Three hypercholesterolaemic patients on maintenance haemodialysis with
      angiographically proven coronary artery disease were treated in a once-a-week
      schedule by combined, synchronous lipid apheresis (using heparin-induced
      extracorporeal LDL precipitation) and haemodialysis (HELP/HD) for 65-104 weeks.
      Clinical side-effects were few and mostly related to high ultrafiltration rates
      in patients with low compliance regarding interdialytic fluid restriction.
      Biocompatibility of the procedure was shown to be good and blood cell losses,
      leukocyte (elastase release) and thrombocyte (beta-thromboglobulin extrusion) as
      well as complement (C3a formation) activation were minimal. Interestingly, most
      of the C3a generated in the extracorporeal HELP circuit was immediately removed
      again in the precipitate filter. In the pseudo-steady-state after 3 months of
      regular therapy, acute haematocrit-corrected reduction of plasma components after
      the session compared to pre values were about 55% for the risk factors LDL
      cholesterol (LDL-C), lipoprotein(a) (Lp(a)), and fibrinogen (FIB) with good
      recovery of HDL-C and other proteins. Urea, creatinine, and phosphate elimination
      was similar to normal haemodialysis. Mean interapheresis values of risk factors
      after one (n = 2) and two (n = 1) years of treatment were crucially dependent
      upon ultrafiltration (UF); thus, in two patients with high UF LDL-C
      concentrations amounting to 185 and 220 mg/dl at baseline and were reduced to
      about 135 mg/dl LDL-C, while in the patient with low UF the reduction was from
      231 mg/dl to 80 mg/dl. The atherogenic index (LDL-C/HDL-C), was reduced from 6.4
      and 5.1 to about 4.3 in patients with high UF, from 6.1 to 3.3 in the patient
      with low UF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159305
TI  - Mediators of complement-independent granulocyte activation during haemodialysis:
      role of calcium, prostaglandins and leukotrienes.
AB  - Granulocyte activation during haemodialysis using cuprophane membrane is mediated
      by complement-derived anaphylatoxins C3a and C5a. However, neutrophil
      degranulation induced by modified cellulosic membranes or synthetic membranes
      does not correlate with C3a or C5a concentrations. Incubation and recirculation
      experiments were performed to find out which messengers trigger neutrophil
      degranulation during blood contact with different membrane materials. During in
      vitro haemodialysis for 2 hours, PMMA and cuprophane induced pronounced
      degranulation of neutrophils. With PMMA this was associated with increased
      thromboxane B2 but low C3a levels, while with cuprophane membrane, marked
      complement activation but only little thromboxane B2 release was observed.
      Indomethacin (10 microM) nullified all thromboxane B2 response but could not
      influence elastase release, indicating that cyclo-oxygenase products are not
      involved in neutrophil degranulation under these conditions. During incubation of
      blood with dialysis membranes, inhibition of lipoxygenase by esculetin or of
      phospholipase A2 by hydrocortisone also had no effect on neutrophil
      degranulation. One messenger involved in granulocyte activation might be free
      cytosolic calcium. Application of different calcium channel blockers (verapamil,
      diltiazem, or nitrendipine) did not influence neutrophil degranulation in
      incubation experiments, in PMMA or cuprophane membranes. In contrast, chelation
      of plasmatic calcium by sodium citrate or EDTA blunted elastase release induced
      by these membranes. This study indicates that calcium is a key mediator required
      for neutrophil degranulation in complement-activating and non-complement
      activating dialysis membranes, while activation of the prostaglandin or
      leukotriene cascade are not required.

PMID- 8159306
TI  - Adequacy of dialysis and nutritional status in CAPD.
AB  - Urea kinetic modelling (UKM) was used to assess adequacy of dialysis in 50 CAPD
      patients. Nutritional status was assessed from the measurement of visceral
      protein status (total protein, albumin, transferrin, immunoglobulins,
      complement), somatic protein status (anthropometry), and dietary intake (1 week
      weighed dietary inventory and normalized protein catabolic rate (NPCR) from UKM).
      Morbidity was assessed from the peritonitis and admission history. Mean Kt/V
      (corrected to x3 weekly dialysis) was 0.66 +/- 0.02. Dietary protein intake
      estimated from the NPCR (1.08 +/- 0.03 g kg-1 day-1) correlated well (r = 0.72, P
      < 0.001) with that estimated from the dietary inventory (1.10 +/- 0.04 g kg-1 day
      1). There was a strong correlation between Kt/V and NPCR corrected for actual
      weight (r = 0.65, P < 0.001), but when NPCR was corrected for IBW this
      correlation was weaker (r = 0.35, P < 0.05). Patients were divided by Kt/V into
      two groups (> 0.65, n = 22 and < 0.65, n = 28). There were no significant
      differences in the indices of visceral protein status between the two groups.
      Weight, height, BMI, fat free mass and arm muscle area were significantly greater
      in the group Kt/V < 0.65. Residual renal function (creatinine clearance) was
      higher in the group Kt/V > 0.65 (3.8 +/- 0.7 versus 1.9 +/- 0.5 1/24 h, P < 0.05)
      and plasma creatinine less (913 +/- 51 versus 1265 +/- 51 mumol/l, P < 0.001).
      Hb, potassium, bicarbonate, phosphate, alkaline phosphatase, PTH, and blood
      pressure were not different. Neither was there any difference between the two
      groups in any of the indices of morbidity.

PMID- 8159307
TI  - Complement activation during CAPD.
AB  - Complement activation was monitored in 20 CAPD patients and 20 normal individuals
      using markers of the alternative (Bb fragment), classical (C4d fragment), common
      (iC3b) and terminal pathways (SC5b-9, the soluble form of the membrane attack
      complex, MAC), together with C3, C4 and factor B. CAPD plasma SC5b-9 was higher
      than normal although this was not due to increased complement activation in the
      plasma. The calculated cleavage for C3, C4 and factor B to iC3b, C4d and Bb
      respectively, due to spontaneous activation, was similar in both groups. C3, C4
      and factor B in dialysate were less than 1% of plasma concentration, consistent
      with vascular leakage, whereas iC3b, Bb and SC5b-9 were at higher concentrations,
      suggesting generation in the peritoneum by the alternative pathway. 2.4% C4d is
      consistent with leakage of this small molecule but may indicate slight classical
      activation. It is concluded that complement activation occurs in the peritoneum
      during CAPD. MAC and the anaphylatoxins which are also generated may contribute
      to an increased risk of infection and other inflammatory complications.

PMID- 8159308
TI  - Acute pancreatitis during CAPD in The Netherlands.
AB  - Acute pancreatitis in patients on CAPD treatment is an infrequent, but serious
      complication. We studied the records of all CAPD patients with acute pancreatitis
      in the Netherlands from 1979 until May 1992. The incidence of acute pancreatitis
      during CAPD treatment was 0.46 per 100 treatment-years. In all patients at least
      one risk factor was present. Hypercalcaemia was the most frequently observed risk
      factor in our patients. The clinical picture consisted of abdominal pain and
      vomiting, with normal temperature and normal peristalsis. Plasma amylase was
      elevated in 18 episodes. Dialysate amylase concentrations exceeded 100 U/l in
      seven of ten episodes. The dialysate could either be clear, haemorrhagic, or
      cloudy. Positive dialysate cultures were found in five patients, in most cases
      with skin flora. No direct correlation with the pancreatitis could be
      established. Mortality was 58%. Continuation of CAPD or transfer to haemodialysis
      had no apparent effect on the outcome, but the best prognosis was found in
      patients with a persistently clear dialysate.

PMID- 8159309
TI  - A case of IgA nephropathy with coeliac disease responding to a gluten-free diet.

PMID- 8159310
TI  - Acute renal failure after a mild physical exercise in idiopathic renal
      hypouricaemia.

PMID- 8159311
TI  - Reversible acute renal failure with calcium oxalate cast nephropathy--possible
      role of ascorbic acid.

PMID- 8159312
TI  - Immune complex glomerulonephritis, myasthenia gravis and compensated
      hypothyroidism in a patient following allogeneic bone marrow transplantation.

PMID- 8159313
TI  - 'Transient multiple myeloma' after intense immunosuppression in a renal
      transplant patient.

PMID- 8159314
TI  - Wound and perinephric haematomata infection with Mycoplasma hominis in a renal
      transplant recipient.

PMID- 8159315
TI  - Prevalence of cholelithiasis in haemodialysis patients.

PMID- 8159316
TI  - Growth factors and progressive renal failure.

PMID- 8159317
TI  - Does captopril decrease the effect of human recombinant erythropoietin in
      haemodialysis patients?

PMID- 8159318
TI  - Pooled human immunoglobulin (PHIG) inhibits the binding of antiendothelial cell
      antibodies to endothelial cells.

PMID- 8159320
TI  - The technology of caring: a synthesis of technology and caring for nursing
      administration.

PMID- 8159319
TI  - Cox "proportional hazards" model.

PMID- 8159321
TI  - Acquired immunodeficiency syndrome (AIDS) has become a universal health care
      dilemma for both patient and provider.

PMID- 8159322
TI  - Each of us has been touched by the worldwide pandemic of human immunodeficiency
      virus (HIV) infection.

PMID- 8159323
TI  - Nursing informatics: networks and databases.

PMID- 8159324
TI  - Nursing dependency needs of HIV-infected patients, Part 1: Methods and clinical
      findings.
AB  - The adequacy with which nurses address the needs of patients infected with the
      human immunodeficiency virus (HIV) depends upon their ability to recognize such
      needs. A 61-item Nurse/Patient Summary was completed on all patients by day shift
      nurses at a tertiary care center. The Nurse/Patient Summary encompasses the
      physical, functional, psychological, and social needs of patients as perceived by
      their nurses. Data were collected from 1987 to 1989. Findings indicate that the
      needs identified by the day shift nurses were congruent on the whole with the
      nursing literature on persons with HIV disease, although some identified needs
      were not adequately explored in the literature. This study does not address
      directly the question as to whether nurses in AIDS units might have identified
      more needs than their nonspecialty colleagues. Using the literature as a proxy,
      however, these findings indicate that nonspecialty nurses are able to identify
      the needs of persons with HIV disease. Thus, specialty units need not be
      predicated on the basis of a lack of nursing expertise in general units.

PMID- 8159325
TI  - Nursing dependency needs of HIV-infected patients, Part 2: Implications for
      management.
AB  - Nurses on undifferentiated patient care units observed significant differences in
      the nursing needs of persons with human immunodeficiency virus (HIV) disease
      compared with other hospitalized patients. These needs were reflected in the
      provision of greater nursing hours per case and greater lengths of hospital stay.
      Less time was spent in the intensive care unit by HIV-infected patients, although
      25 percent died in the hospital. There were few HIV patients overall, but given
      the percentage dying, additional support services may be required in the
      community to enable terminally ill persons to die at home or in a similar low
      technology environment.

PMID- 8159326
TI  - Development of a measure of willingness to provide nursing care to AIDS patients.
AB  - The Nursing Willingness Questionnaire (NWQ) was developed to measure nurses'
      willingness to perform specific direct care activities for an adult male patient
      with acquired immunodeficiency syndrome (AIDS). Measures of internal consistency
      and one-week test-retest stability indicated excellent reliability. NWQ scale
      scores correlated significantly with a measure of fear of contracting AIDS via
      interpersonal and medical contacts but not with fear of contagion through risky
      sexual behavior. In principle components analysis, all items loaded on one
      factor. These psychometric studies suggest the NWQ is a reliable and valid
      instrument for evaluating a construct of current concern to nursing
      administrators and educators.

PMID- 8159327
TI  - The AIDS epidemic: caring for caregivers.
AB  - AIDS has become a global health problem for individuals, families and health care
      providers. This disease has a tremendous impact on the physical and psychological
      well-being of these groups. Nurses are on the front line providing physical care
      and support for these patients and their families; but nurses also need support
      and caring as they carry out their important nursing roles. This article
      addresses the effects of AIDS on nurses and presents a model for nursing
      administrators to establish and maintain a supportive, caring environment for
      nurses.

PMID- 8159328
TI  - The impact of AIDS on recruitment and retention in hospitals.
AB  - Little is reported about the impact of AIDS on the recruitment and retention of
      nurses in hospitals. The author reports a statewide survey of problems and
      strategies in recruiting and retaining nurses to care for AIDS patients. The
      major problems identified were fear of contagion, the need for strong educational
      training, and the complex care requirements of AIDS patients. Strategies for
      recruitment included financial incentives and intensive educational programs.

PMID- 8159329
TI  - Authentic caring: the sensible answer for clients and staff dealing with
      HIV/AIDS.
AB  - The Denver Nursing Project in Human Caring is a nurse-managed outpatient center
      providing integrated care and services for persons living with HIV/AIDS, their
      family members, and friends. The center is collaboratively sponsored by three
      Denver hospitals and the University of Colorado School of Nursing. Programs and
      services of the center are based on Watson's theory of human care nursing. The
      ongoing challenge to operationalize authentic caring has resulted in growth and
      satisfaction for both clients and staff. In addition, the center has documented
      its cost effectiveness for the participating institutions.

PMID- 8159330
TI  - A multidisciplinary, multifaceted HIV program: linking the resources.
AB  - The current and potential impact of the human immunodeficiency virus (HIV)
      disease on the financial and human resources of institutions requires strategic
      planning by health care administrators and providers. The HIV disease devastates
      the lives of many individuals, and it continues to impact the health care
      industry with accelerating force. Fairfax Hospital has developed a comprehensive
      HIV program to address the current needs of people afflicted with this disease
      and to manage for the future. Goals and strategies are discussed.

PMID- 8159331
TI  - The structure and functions of an ambulatory care center for HIV/AIDS.
AB  - For the past decade, the spread of HIV infection in the United States has been
      marked by dramatic growth, increasing diversity in the population affected, a
      widening geographic focus and a broadened clinical spectrum. In response to this,
      the Ambulatory Care Center (ACC) of Jackson Memorial Hospital (JMH) has provided
      a structure for clients with HIV/AIDS that is easily accessible, comprehensive,
      and confidential. Committed staff provide care for these clients in a humanistic,
      caring and effective manner.

PMID- 8159332
TI  - An integrated case management model: developing standards, evaluation, and
      outcome criteria.
AB  - Case management has become an important strategy in responding to the complex
      physical and social needs of persons with human immunodeficiency virus (HIV)
      disease. Yet, inconsistent implementation and professional turf guarding, based
      on disciplinary differences, have rendered traditional models ineffective. AID
      Atlanta has adopted an integrated, multisite approach to case management that
      uses the expertise of social workers, nurses, pastoral counselors, and therapists
      to develop client-centered plans of care across the continuum of need. This
      article presents the integrated model and describes the standards of service and
      outcome evaluation criteria that underpin this model. The impact of nursing
      expertise on the development of the model is discussed.

PMID- 8159333
TI  - A computer-based approach to quality improvement for telephone triage in a
      community AIDS clinic.
AB  - Observation of the current procedure for telephone triage in a community-based
      acquired immunodeficiency syndrome (AIDS) clinic and a retrospective chart audit
      identified opportunities for improvement in the process for the management of
      telephone triage encounters. Specifically, it pointed out that the nurses faced
      difficulties in accessing relevant clinical data, and that a large number of data
      were missing in the documentation for the encounter. Five design goals for a
      computer-based system to improve the management of the telephone triage encounter
      were generated by an interdisciplinary project team. A computer-based approach to
      management of the telephone triage encounter complemented by the development of
      performance standards and guidelines has the potential to improve both the
      process of telephone triage and the documentation of the triage encounter.

PMID- 8159334
TI  - HIV/AIDS training for health care providers working with women at risk.
AB  - Diagnosis of HIV/AIDS in women is frequently inadequate. Often women are not
      assessed for risk behaviors that put them at risk for HIV infection. Viral
      transmission is preventable through behavioral changes. Past experience has
      demonstrated that one effective method to educate women at risk is to train
      direct care providers who work with women. Highly skilled providers with
      expertise in prevention education strategies can facilitate and support
      behavioral changes in women at risk for HIV transmission.

PMID- 8159335
TI  - Educating advanced practice nurses to respond to the HIV pandemic.
AB  - The subspecialization in the master's degree nursing program at Hunter College is
      preparing a cadre of nursing leaders and expert clinicians through formal
      didactic courses and clinical placements with master's prepared nurses who work
      in HIV/AIDS. The HIV/AIDS subspecialty option is offered to graduate nursing
      students in all of the six specialties: medical-surgical, psychiatric-mental
      health nursing, maternal-child nursing, community health nursing, gerontological
      nurse practitioner program, and nursing administration. The terminal objectives
      for the graduate program serve as the framework for the terminal objectives of
      the subspecialty and primary, secondary, and tertiary levels of prevention serve
      as the conceptual framework. The clinical aspect of the HIV/AIDS subspecialty
      content is coordinated within the specialization component in that the final
      advanced practicum in the student's specialty is with a master's prepared nursing
      preceptor who is caring for persons with HIV/AIDS.

PMID- 8159336
TI  - Mandatory HIV testing: a position paper.
AB  - This article takes the position that mandatory testing of health workers for HIV
      is unethical because it is a misuse of resources. This is an ethical dilemma in
      distributive justice. Six facts are detailed to support this position.

PMID- 8159337
TI  - Computer networks show great promise in supporting AIDS patients.

PMID- 8159339
TI  - Software applications and functions for managed care (third in a three-part
      series).

PMID- 8159338
TI  - Utilization and importance of 10 components of a nursing delivery system in long
      term care (a predecentralization study).

PMID- 8159340
TI  - Premature discharge.

PMID- 8159341
TI  - Of confidentiality, co-workers and adoption.

PMID- 8159342
TI  - Healthcare reform: innovations at the state level. Coopers & Lybrand Health
      Decisions Resource Group.
AB  - States are struggling to devise politically acceptable ways to curb rising
      healthcare costs while improving access for their uninsured residents. In
      general, their reform strategies attempt to increase access to quality healthcare
      services, reform the health insurance industry, and control healthcare costs.
      Additionally, states have enacted laws that provide reform in the areas of
      medical malpractice, the health planning process, provider availability and scope
      of practice, the pharmaceutical industry, and the Medicaid program.

PMID- 8159343
TI  - GME financing: a well-kept secret.
AB  - Comprehensive healthcare reform depends on our ability to educate more primary
      care providers and reduce the oversupply of specialists and subspecialists.
      However, significant financial incentives exist, hidden within the Federal
      reimbursement system to fuel continued growth of highly specialized physicians,
      undermining efforts to educate primary care practitioners. If Medicare cannot
      correct this situation, perhaps the government should redirect GME funds to
      educate nurse practitioners.

PMID- 8159344
TI  - ME changes: effects on patient care delivery.
AB  - The Health Care Financing Administration consolidated Durable Medical Equipment
      (DME) processing into four regional DME carriers for Medicare. These four DMERCs
      Durable Medical Equipment Regional Carriers (DMERCs) will process claims more
      accurately, reduce variations in coverage decisions, and decrease the
      opportunities for fraud. Taken in its entirety, the DME regionalization process
      is a major step toward achieving nationally consistent expectations for quality
      of care.

PMID- 8159345
TI  - Capacity and competence: nurse credentialing and privileging.
AB  - Ideally, patient needs are carefully matched with nursing skills, but despite the
      use of tools such as patient classification systems, matching needs with
      capabilities remains problematic. To effectively confront this problem, hospitals
      have a model to manage professionals with disparate education, training and
      experience--the medical staff credentialing and privileging program. Although
      adaptation of this model requires a significant cultural change for most nursing
      departments, it offers the benefits of fostering professionalism and increasing
      accountability in addition to better meeting patient care needs. In return for
      their initial investment, nurse executives may see results that include a more
      responsive, professional staff and increased customer satisfaction, both internal
      and external.

PMID- 8159346
TI  - Evaluation of two planned change theories.
AB  - The Tiffany/Lutjens Planned Change Theory Evaluation Scale guides nurses in
      choosing an effective planned change theory. The scale asks many questions
      specifically related to the relevance of a change theory to nursing concerns such
      as significance, economy, practicality and congruence with nursing's perspective.
      Appropriate applications of two change theories to nursing situations are
      discussed.

PMID- 8159347
TI  - Nursing unit managers: defining a role.
AB  - Using Katz's classification scale, a panel of experts--nurse managers, nurse
      academics and professional and industrial nursing organization representatives-
      identified roles expected of first-line nursing managers in New South Wales
      hospitals. The 156 competencies defined by this group were classified into
      technical, human and conceptual skills. Classifications determine the manager's
      responsibilities, authority and performance accountability.

PMID- 8159348
TI  - Home health nursing: towards a professional practice model.
AB  - A rapidly growing caseload led this home healthcare agency in New England to
      develop and implement a new management structure built around the belief that 1)
      Professionals can manage their own practice and function as part of a self
      directed work team; 2) Management's role is to foster an organizational culture
      which facilitates this; and 3) Total quality management is based on people
      oriented service. A "flex-time" system, competitive compensation and empowerment
      stemming from responsible autonomy have begun to reduce turnover and enhance
      "word of mouth" advertising.

PMID- 8159349
TI  - The tsunami effect.

PMID- 8159350
TI  - Unit-based shared governance can work!
AB  - The Nurse Executive Council at a 540-bed community teaching health center planned
      and implemented Shared Governance in a 10-bed Medical Intensive Care Unit (MICU).
      Paid time was provided for nurses to take part in one of four councils. After a
      pilot year resulting in satisfaction with job autonomy and input into decision
      making, staff reaffirmed their commitment to shared governance as a permanent
      "way of life" in the MICU. During the second year, patient care assistants and
      unit clerks were integrated into the Councils and staff began serving as
      consultants to other units and institutions.

PMID- 8159351
TI  - Discharge planners and cost containment.
AB  - Discharge planners play an important role in managing healthcare costs. Until
      recent years, the actual dollar costs of healthcare were not a concern of either
      healthcare providers or patients. This author studied the level of knowledge
      discharge planners have of actual dollar costs of healthcare, their perception of
      the patient's level of knowledge, and the impact of the knowledge on healthcare
      decisions.

PMID- 8159352
TI  - Self-scheduling: an innovative approach.
AB  - Self-scheduling provides staff nurses the opportunity to be autonomous and to
      control their work schedules. Formation of a committee which will develop short
      term and long-term goals is a critical first step. From an administrative
      standpoint, the staff's increased awareness of staffing and scheduling issues
      results in many long-term benefits for staff development and retention.
      Unscheduled absences due to illness decrease, as do individual requests for
      changes after posting of the schedule. The accountability and responsibility
      fostered leads to job satisfaction and professional growth.

PMID- 8159353
TI  - Mandated infection control.

PMID- 8159354
TI  - Establishing a personal financial plan.

PMID- 8159355
TI  - Pregnancy complicated by primary antiphospholipid antibody syndrome.
AB  - BACKGROUND: Primary antiphospholipid antibody syndrome is a clinical entity that
      may threaten the health of both fetus and mother. CASE: We report a fatal case of
      primary antiphospholipid antibody syndrome in a woman who developed catastrophic
      disease due to multisystem thrombosis in the postpartum period following a fetal
      death. Three years before her admission, primary antiphospholipid antibody
      syndrome was diagnosed on the basis of high titers of immunoglobulin G
      anticardiolipin antibody, a positive lupus anticoagulant, a false-positive VDRL,
      and fibrin deposits in the biopsy of a palmar lesion. CONCLUSION: The physician
      must recognize the potentially catastrophic complications of pregnancy and the
      postpartum period in patients with antiphospholipid antibodies, and appropriate
      patient counseling should be provided.

PMID- 8159356
TI  - Severe postpartum pulmonary, cardiac, and renal syndrome associated with
      antiphospholipid antibodies.
AB  - BACKGROUND: The antiphospholipid antibody syndrome has been associated with
      thromboembolic events, thrombocytopenia, fetal death, fetal growth retardation,
      and early-onset severe preeclampsia. CASE: A postpartum woman developed fever,
      pulmonary infiltrates, cardiac conduction defects, and renal insufficiency
      following severe preeclampsia. She tested positive for lupus anticoagulant and
      anticardiolipin antibody, and responded to steroid therapy and plasmapheresis.
      CONCLUSION: The postpartum multi-system involvement suggests that a variety of
      clinical presentations may be associated with antiphospholipid antibodies.
      Treatment with plasmapheresis or corticosteroids may be of value in similar
      cases.

PMID- 8159357
TI  - Acute promyelocytic leukemia in pregnancy: all-trans retinoic acid as a newer
      therapeutic option.
AB  - BACKGROUND: Acute promyelocytic leukemia is a unique subset of acute myelogenous
      leukemia, characterized by a neoplastic proliferation of promyelocytes and a
      prompt response to all-trans retinoic acid (tretinoin), which induces
      differentiation of immature leukemic promyelocytes into mature neutrophils.
      Because of the high incidence of disseminated intravascular coagulation (DIC)
      associated with acute promyelocytic leukemia and the danger of exacerbation of
      DIC with pregnancy, management of acute promyelocytic leukemia during pregnancy
      requires prompt and careful attention. CASE: A 29-year-old woman in her third
      trimester was diagnosed with acute promyelocytic leukemia and DIC. The infant was
      delivered by cesarean and the mother was successfully treated with tretinoin,
      inducing the leukemic promyelocytes to differentiate into mature granulocytes and
      possibly reversing the DIC. CONCLUSION: If the fetus can be delivered safely,
      tretinoin as a single agent is an option for the initial treatment of maternal
      acute promyelocytic leukemia because it does not suppress the bone marrow and may
      ameliorate DIC. Because of the danger of hyperleukocytosis, chemotherapy should
      be added initially if the white blood cell count is greater than 5000/microL. If
      the fetus cannot be delivered at a viable stage, conventional cytotoxic
      chemotherapy is the alternative option.

PMID- 8159358
TI  - Pregnancy in a patient with eosinophilic granulomatosis of the lung: a case
      report.
AB  - BACKGROUND: There are three syndromes of histiocytosis X: eosinophilic
      granulomatosis of the lungs, Hand-Schuller-Christian disease, and Letterer-Siwe
      disease. Although there have been five case reports of Hand-Schuller-Christian
      disease in pregnancy, we found none describing pregnancy in patients with
      eosinophilic granulomatosis. CASE: We present a report of eosinophilic
      granulomatosis of the lungs in pregnancy. The patient's pregnancy was complicated
      by fetal growth retardation (FGR) and oligohydramnios, but resulted in the
      delivery of a healthy infant. Her pulmonary disease remained stable. CONCLUSION:
      Pregnancy does not appear to exacerbate pulmonary eosinophilic granulomatosis. In
      this patient, pregnancy was complicated by FGR and oligohydramnios. This case
      report may be valuable in counseling patients with eosinophilic granulomatosis
      who are currently pregnant or contemplating pregnancy.

PMID- 8159359
TI  - Beckwith-Wiedemann syndrome, placental abnormalities, and gestational proteinuric
      hypertension.
AB  - BACKGROUND: Beckwith-Wiedemann syndrome is a genetically complex congenital
      disorder with variable clinical features at birth, including malformations,
      excessive body and/or organ growth, and endocrine dysfunction. Both maternal
      gestational proteinuric hypertension and placental abnormalities have been
      reported infrequently in Beckwith-Wiedemann syndrome, but the occurrence of three
      cases with both features at one institution within a year suggests that this may
      be an underreported association. CASES: Severe gestational proteinuric
      hypertension in three women led to termination of one pregnancy at 22 weeks'
      gestation, delivery by cesarean in another at 27 weeks of an infant who had
      hyperinsulinism and died at age 3 days, and stillbirth at 31 weeks in the third.
      All three infants had features diagnostic of Beckwith-Wiedemann syndrome.
      Placentomegaly had been identified by ultrasound in each case and was determined
      pathologically as mainly attributable to stromal expansion of the villous tree.
      Cysts resulting from hydrops in stem villi were identified ultrasonographically
      in one placenta; this lesion may be specific for Beckwith-Wiedemann syndrome. The
      third placenta was associated with a discrete complete hydatidiform mole.
      CONCLUSIONS: A diagnosis of Beckwith-Wiedemann syndrome should be considered in
      all cases in which gestational proteinuric hypertension is associated with
      ultrasound findings of placentomegaly, with or without associated cystic changes
      in the placenta, and an examination should be made for other confirmatory
      features.

PMID- 8159360
TI  - Renal cell carcinoma in pregnancy: report of three cases and review of the
      literature.
AB  - BACKGROUND: Renal cell carcinoma is a potentially fatal tumor that occasionally
      presents during pregnancy. Based on our experience with three patients and a
      review of the recent cases in the literature, we believe there has been a change
      in presentation of this lesion over that described in previous reviews. CASES:
      Two of three women with renal cell carcinoma found during pregnancy had symptoms
      suggesting recurrent urinary tract infection. The renal tumors were all
      discovered by ultrasound. In addition, magnetic resonance imaging was used for
      preoperative, intragestational staging of one patient. CONCLUSION: Renal cell
      carcinoma should be considered in women of childbearing age who present with
      recurrent or refractory urinary tract symptoms, flank pain, or a palpable flank
      mass. Ultrasound appears to be the imaging procedure of choice for evaluating the
      urinary system in pregnant women.

PMID- 8159361
TI  - Recurrent pheochromocytoma during pregnancy.
AB  - BACKGROUND: Pheochromocytoma recurs commonly. The treatment for pheochromocytoma
      is adrenalectomy, and successful pregnancy has been achieved after bilateral
      adrenalectomy. Recurrent pheochromocytoma in pregnancy carries a high risk for
      mother and fetus. CASE: A primigravid woman with prior bilateral adrenalectomy
      for pheochromocytoma was followed during her pregnancy with careful attention to
      the possibility of tumor recurrence. Maternal tachycardia, elevated urinary
      catecholamines, and rising hematocrit levels indicated recurrence of the
      pheochromocytoma at 18 weeks' gestation. Medical therapy and antenatal testing
      were instituted. Labor was induced at 36 weeks' gestation because of decreasing
      amniotic fluid volume, and a healthy 2649-g infant was delivered vaginally. No
      maternal complications occurred in the postpartum period. CONCLUSION: One of the
      signs of recurrent pheochromocytoma is hemoconcentration which, in combination
      with increased catecholamines, may lead to uteroplacental insufficiency. With
      intense surveillance, good outcomes may be achieved.

PMID- 8159362
TI  - Respiratory failure in pregnancy due to Pneumocystis carinii: report of a
      successful outcome.
AB  - BACKGROUND: The incidence of infection with the human immunodeficiency virus
      (HIV) is rising rapidly among women of reproductive age. Pneumocystis carinii
      pneumonia during pregnancy may be the first manifestation of HIV infection. If
      respiratory failure ensures, the outcome has been reported as almost invariably
      fatal. CASE: A 31-year-old African-American woman at 28 weeks' gestation was
      admitted with bilateral perihilar interstitial infiltrates. Laboratory evaluation
      revealed hypoxemia and an elevated serum lactic dehydrogenase level. Although she
      denied risk factors for HIV infection, she was treated immediately for P carinii
      infection with trimethoprim-sulfamethoxazole and methylprednisolone. Her
      respiratory status deteriorated and she required intubation. Bronchoscopy
      confirmed the diagnosis, and CD4 lymphocyte depletion confirmed
      immunosuppression. The patient responded to treatment and recovered completely.
      CONCLUSION: A high index of suspicion must be maintained for the diagnosis of P
      carinii and previously unsuspected HIV infection during pregnancy. The early
      manifestations may be subtle and progress over weeks until respiratory failure
      rapidly ensues. With timely diagnosis and management, the outcome of P carinii
      pneumonia in pregnancy can be successful.

PMID- 8159363
TI  - Pregnancy complicated by thrombocytopenia secondary to human immunodeficiency
      virus infection.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-positive pregnant women may
      manifest thrombocytopenia similar to that of immune thrombocytopenic purpura
      (ITP), putting the fetus at risk of thrombocytopenia and hemorrhage. Whereas the
      fetal platelet count can be assessed in cases of ITP, there is no safe way to
      evaluate it during HIV-positive pregnancy without risking fetal inoculation with
      HIV. CASE: A pregnant woman with HIV-associated autoimmune thrombocytopenia was
      treated on several occasions with immune globulin and prednisone. Because of the
      inability to assess the fetal platelet count owing to the risk of fetal
      inoculation with maternal HIV, a primary cesarean was performed at term. The
      neonate was thrombocytopenic at birth. CONCLUSION: Because of the risk of fetal
      thrombocytopenia and the inability to evaluate fetal platelet counts safely
      (without resorting to invasive procedures that may increase the risk of fetal HIV
      infection), women with HIV-associated autoimmune thrombocytopenia should be
      delivered by cesarean.

PMID- 8159364
TI  - Diamond-blackfan anemia in pregnancy.
AB  - BACKGROUND: Diamond-Blackfan anemia is a rare form of congenital red-cell
      aplasia. Approximately 90% of the patients are diagnosed by 1 year of age. This
      report presents two pregnancies with good outcomes in a patient over a period of
      1.5 years. CASE: The patient, a 20-year-old woman, was diagnosed with Diamond
      Blackfan anemia at age 3.5 months. Treatments consisted of red blood cell
      transfusions and oral corticosteroids. She conceived at age 18 years and
      delivered prematurely at 34 weeks' gestation. Her second pregnancy was diagnosed
      4 months after delivery of the first child, and she delivered spontaneously at 38
      weeks and 6 days' gestation. She received multiple blood transfusions during both
      of the pregnancies. The infants were average for gestational age and had normal
      examination at birth. CONCLUSION: Based on this case and a review of the
      literature, it appears that pregnancy and birth control pills may contribute to
      the relapse of anemia in patients diagnosed with Diamond-Blackfan syndrome. This
      may require an increase in the frequency of blood transfusions. Pregnancies are
      usually tolerated well and can be managed with supportive therapy.

PMID- 8159365
TI  - Latrodectus mactans (black widow spider) envenomation: an unusual cause for
      abdominal pain in pregnancy.
AB  - BACKGROUND: The differential diagnosis of abdominal pain in pregnancy is
      extensive. An important consideration in endemic areas is a bite by a black widow
      spider. CASE: A 30-year-old woman at 30 weeks' gestation presented with acute
      abdominal pain following an insect bite. We based the diagnosis on classic
      symptomatology in an area endemic for Latrodectus mactans. Treatment consisted of
      supportive therapy and observation. Symptoms resolved over 48 hours and did not
      recur. The patient delivered a healthy child at 40 weeks' gestation. CONCLUSION:
      In endemic areas, black widow spider envenomation should be part of the
      differential diagnosis of abdominal pain in pregnancy.

PMID- 8159366
TI  - Primary adenocarcinoma of the gallbladder presenting as primary gynecologic
      malignancy: a report of two cases.
AB  - BACKGROUND: Carcinoma metastatic to the uterus from extragenital sites is rare.
      Such metastatic disease is typically diagnosed at autopsy or in patients with
      known primary malignancies. This report discusses two cases of primary carcinoma
      of the gallbladder presenting as abnormalities in gynecologic screening
      procedures. CASES: A 71-year-old woman presented with postmenopausal bleeding.
      Uterine curettage revealed poorly differentiated adenocarcinoma of presumed
      endometrial origin. Intraoperative frozen-section analysis of the uterus showed
      carcinoma involving the lymphatics, but no primary tumor. Further exploration
      revealed primary adenocarcinoma of the gallbladder, with widespread metastases.
      The second case was a 67-year-old asymptomatic woman. Routine cervical cytology
      showed adenocarcinoma, but tissue studies were negative. She developed jaundice 1
      month later. Computed tomography of the upper abdomen revealed a mass in the
      gallbladder fossa, and needle biopsy of the lesion showed adenocarcinoma.
      CONCLUSIONS: Metastatic carcinoma of non-genital tract origin may present as
      primary gynecologic malignancy. The physician should be aware of the implications
      of both the common and unusual interpretations of screening and diagnostic
      procedures. When the clinicopathologic presentation is atypical, a thorough
      knowledge of the differential diagnoses of abnormal test results allows
      appropriate and expeditious patient management.

PMID- 8159367
TI  - Parvovirus B19 infection in a twin pregnancy.
AB  - BACKGROUND: Parvovirus infection has been associated with the development of
      nonimmune hydrops fetalis in pregnancy. This report describes a twin pregnancy in
      which one fetus was affected by parvovirus B19 and the other was not. CASE: A 35
      year-old woman was found to have a twin gestation at genetic amniocentesis.
      Subsequent ultrasound at 18 weeks showed that twin B had evidence of hydrops
      fetalis. Serum from the mother tested positive for parvovirus B19 immunoglobulin
      (Ig) G and IgM. Cultured amniotic fluid from twin B was subsequently found to be
      positive for parvovirus B19. At 20 weeks' gestation, the hydropic fetus died. The
      unaffected fetus grew normally. At 40 weeks, the unaffected fetus was delivered
      vaginally with no difficulties. Cord blood from the unaffected fetus was negative
      for parvovirus B19 IgM. CONCLUSION: This case demonstrates differential infection
      of parvovirus B19 in a diamniotic, dichorionic twin pregnancy. One twin developed
      signs of hydrops fetalis consistent with parvovirus B19. The diagnosis was
      confirmed immunologically and by amniotic fluid culture. The second twin had no
      evidence of parvovirus B19 and no immunologic suggestion of infection at birth.
      This is the only known report of such differential transmission of parvovirus B19
      in a twin pregnancy.

PMID- 8159368
TI  - Intrauterine pregnancy following endometrial ablation.
AB  - BACKGROUND: Only five pregnancies have been reported after endometrial ablation
      by resectoscopic endometrial resection, for a rate of 0.7% on the basis of three
      series. CASE: Endometrial ablation was performed using a roller-ball electrode on
      a 37-year-old woman who had menorrhagia and dysmenorrhea. She subsequently
      conceived but experienced a missed abortion. CONCLUSION: Pregnancy is a rare
      occurrence following endometrial ablation. The effect of endometrial ablation on
      pregnancy outcome is unknown.

PMID- 8159369
TI  - Uterine rupture during pregnancy in a patient with a history of hysteroscopic
      metroplasty.
AB  - BACKGROUND: Uterine septa may be responsible for spontaneous abortion.
      Hysteroscopic metroplasty may improve pregnancy outcome. CASE: A patient with a
      history of hysteroscopic resection of a uterine septum presented in preterm
      labor. This was her second pregnancy following the procedure; the first resulted
      in a term vaginal delivery. This second pregnancy ended with a preterm cesarean
      delivery. A 3.5 x 3.5-cm fundal rupture was discovered during the cesarean. The
      metroplasty had been performed with the KTP laser under direct laparoscopic
      visualization. No surgical complications had occurred. CONCLUSIONS: Uterine
      rupture during a pregnancy may occur following hysteroscopic metroplasty, even
      when no complications occur at surgery and even if a normal pregnancy outcome
      follows the procedure. Physicians providing care for patients who have had
      hysteroscopic metroplasty should be aware of the potential for uterine rupture
      during pregnancy.

PMID- 8159370
TI  - Uterine rupture associated with recent antepartum cocaine abuse.
AB  - BACKGROUND: The diagnosis of uterine rupture is aided by the identification of
      risk factors, such as oxytocin administration. In several experiments, cocaine
      has been shown to stimulate uterine contractility. Complications from cocaine
      abuse during pregnancy have increased dramatically in the United States, and
      cocaine may increase the risk for uterine rupture. CASES: Two cases of uterine
      rupture were associated with recent cocaine abuse. CONCLUSION: These cases and
      recent experiments on the effect of cocaine on the pregnant uterus suggest that
      antepartum cocaine abuse may increase the risk of uterine rupture.

PMID- 8159371
TI  - Intrapartum uterine rupture in a primiparous patient previously treated for
      invasive mole.
AB  - BACKGROUND: Intrapartum rupture of the uterus in a primiparous patient is an
      exceedingly rare event. This case report describes uterine rupture in a woman
      with previous invasive hydatidiform mole. CASE: A 27-year-old primiparous woman
      with a history of gestational trophoblastic neoplasia treated successfully with
      chemotherapy experienced intrapartum uterine rupture with subsequent neonatal
      death. Magnetic resonance imaging of the uterus had shown evidence of myometrial
      invasion by the mole. Weakening of the uterine wall secondary to myometrial
      destruction is believed to have caused the uterine rupture. CONCLUSION: Many
      women will attempt to conceive following treatment for gestational trophoblastic
      neoplasia. It is important to determine whether there is any local invasion of
      the myometrium, as this can affect intrapartum management in subsequent
      pregnancies.

PMID- 8159372
TI  - Nonsurgical management of placenta percreta: a case report.
AB  - BACKGROUND: Although placenta percreta is rare, its sequelae include potentially
      lethal hemorrhage and loss of reproductive function. Therapy directed toward
      control of life-threatening hemorrhage frequently includes emergency
      hysterectomy. CASE: A woman with placenta percreta, suspected clinically and
      documented radiographically, was treated nonsurgically. Following delivery, the
      placenta was left in situ and methotrexate chemotherapy was initiated to aid
      destruction of the trophoblastic tissue. Eight months later, hysteroscopy showed
      a normal uterine cavity with only a small area of calcification at the presumed
      implantation site. Two years later, the patient had a normal pregnancy and
      vaginal delivery. CONCLUSION: Placenta percreta can be managed with preservation
      of the uterus, but careful follow-up may be required until the entire placenta
      has resorbed.

PMID- 8159373
TI  - Sixth nerve palsy: an unusual manifestation of preeclampsia.
AB  - BACKGROUND: Neurologic abnormalities may occur in pregnancy as a manifestation of
      neurologic or systemic disease. We present an unusual case of preeclampsia
      presenting with a sixth nerve lesion. CASE: A 33-year-old woman, gravida 2,
      presented at 38 weeks' gestation with sixth nerve palsy. She was hypertensive and
      proteinuric, with plasma urea of 24 mg/dL. Labor was induced and hypertension
      escalated in the early puerperium, with concomitant worsening diplopia. Blood
      pressure control and resolution of preeclampsia were followed by resolution of
      the sixth nerve lesion. There was no evidence of other pathology on extensive
      investigations. CONCLUSION: Sixth nerve palsy is an unusual manifestation of
      preeclampsia.

PMID- 8159374
TI  - Amniotic fluid embolism after saline amnioinfusion: two cases and review of the
      literature.
AB  - BACKGROUND: Amnioinfusion is an intrapartum intervention with proven benefit in
      certain clinical situations. It is thought to be a safe treatment with few
      adverse effects. CASES: Two cases of fatal amniotic fluid (AF) embolism occurred
      in women who were treated during labor with a saline amnioinfusion. In both
      cases, amnioinfusion was administered after finding thick meconium staining of
      the AF. In addition to the amnioinfusion, common factors in these cases and three
      previously reported AF embolisms associated with amnioinfusion are the presence
      of rapid labor, meconium-stained fluid, or both. CONCLUSIONS: Amniotic fluid
      embolism is a rare cause of maternal morbidity and mortality. It is not known
      whether amnioinfusion increases the rate of its occurrence in laboring patients.
      No change in clinical practice is warranted on the basis of these reports;
      however, future reports must be examined so that any common factors can be
      identified.

PMID- 8159375
TI  - The real-time and color Doppler appearance of adrenal neuroblastoma in a third
      trimester fetus.
AB  - BACKGROUND: Neuroblastoma is the second most common malignant tumor of childhood.
      With the increasing use of ultrasound, prenatal recognition of this tumor is
      becoming more common. CASE: A 33-year-old woman presented at 38 weeks' gestation.
      A mass at the level of the left fetal renal pole was identified upon
      ultrasonography. Color Doppler and flow mapping were also evaluated. CONCLUSION:
      Ultrasound evaluation, color flow mapping, and Doppler flow studies of fetal
      neuroblastoma may be helpful in both diagnosis and management.

PMID- 8159376
TI  - Prenatal diagnosis of cleidocranial dysostosis.
AB  - BACKGROUND: Cleidocranial dysostosis is an autosomal dominant disorder
      characterized by absent or hypoplastic clavicles and dysplasia of the osseous
      tissue in the cranium. CASE: We describe the prenatal diagnosis and neonatal
      evaluation of cleidocranial dysostosis in the pregnancy of a woman also affected
      with this disorder. CONCLUSION: The sonographic appearance of absent or
      hypoplastic clavicles, in the absence of other findings suggesting a skeletal
      dysplasia, strongly suggests the diagnosis of cleidocranial dysostosis. Nomograms
      are available to follow the growth and development of normal clavicles.
      Assessment of normal long-bone growth in relation to clavicular size may aid in
      the diagnosis.

PMID- 8159377
TI  - Prenatal sonographic diagnosis of non-rhizomelic chondrodysplasia punctata.
AB  - BACKGROUND: Chondrodysplasia punctata is a rare heterogeneous group of bone
      dysplasias occurring with an incidence of one in 100,000 live births. Prenatal
      sonographic diagnosis of non-rhizomelic chondrodysplasia punctata (Conradi
      Hunermann syndrome) has previously been reported only following detection of
      overall limb shortening. CASE: Multiple sonographic skeletal findings of
      premature epiphyseal calcifications, other unusual calcifications,
      kyphoscoliosis, and asymmetrical limb shortening, typical of non-rhizomelic
      chondrodysplasia punctata, led to second-trimester prenatal sonographic diagnosis
      of this condition. CONCLUSION: Second-trimester prenatal sonographic diagnosis of
      premature epiphyseal calcifications associated with non-rhizomelic
      chondrodysplasia punctata is possible.

PMID- 8159378
TI  - Prenatal ultrasound findings of linear nevus sebaceous and its association with
      cystic adenomatoid malformation of the lung.
AB  - BACKGROUND: Nevus sebaceous is a congenital hamartomatous skin lesion that is
      commonly associated with other abnormalities and is most frequently located on
      the face and head. To our knowledge, there are no previous reports of the
      ultrasonographic appearance of nevus sebaceous or of an association with cystic
      adenomatoid malformation of the lung. CASE: A patient was referred at 25 weeks'
      gestation with multiple fetal anomalies, including echogenic soft-tissue
      structures external to the cranium and face, a large right-side intrathoracic
      mass, and abdominal ascites. After a preterm delivery, nevus sebaceous and a
      congenital cystic adenomatoid malformation of the lung were diagnosed. Neonatal
      death occurred secondary to pulmonary hypoplasia. CONCLUSION: Nevus sebaceous
      should be considered in the differential diagnosis when echogenic soft-tissue
      structures are seen on prenatal ultrasound. A detailed ultrasound examination is
      warranted to rule out other associated abnormalities.

PMID- 8159379
TI  - Umbilical artery steal syndrome and distal gangrene in a case of twin-twin
      transfusion syndrome.
AB  - BACKGROUND: Vascular accidents in the survivor from pregnancies with twin-twin
      transfusion syndrome have been attributed to the release of thromboplastin from
      the dead fetus. CASE: In a woman presenting at 22 weeks' gestation with acute
      polyhydramnios due to twin-twin transfusion syndrome, endoscopic laser
      coagulation of the communicating vessels was performed. At endoscopy, the toes of
      the left foot of the recipient fetus were noted to be gangrenous. This fetus had
      only a left umbilical artery, which was markedly dilated, and Doppler studies
      demonstrated impaired perfusion of the left leg. In four control fetuses with a
      single umbilical artery, Doppler studies demonstrated normal waveforms in both
      legs. CONCLUSION: In twin-twin transfusion syndrome, fetal peripheral gangrene
      may occur before the death of one twin. The ischemic necrosis of the toes
      probably resulted from the combined effect of polycythemia and umbilical artery
      steal syndrome. Interruption of twin-twin transfusion syndrome caused resolution
      of the polycythemia and prevented further damage by removing one of the
      components of the peripheral ischemia.

PMID- 8159380
TI  - Etiology of prune belly syndrome: evidence of megalocystic origin in an early
      fetus.
AB  - BACKGROUND: Prune belly syndrome is a rare and complicated condition affecting
      the genitourinary organs and abdominal wall. The etiology of abdominal
      musculature deficiency in prune belly syndrome is controversial. We present a
      case that should elucidate the etiology of this syndrome. CASE: A spontaneously
      aborted fetus at 12 weeks' gestation with an early stage of prune belly syndrome
      was investigated by necropsy and light and electron microscopy. Megalocystis
      resulting from urethral atresia was diagnosed. There was no hydroureter or
      hydronephrosis, and both light and electron microscopy demonstrated evidence of
      development of the abdominal musculature. Both testes were elevated as a result
      of the megalocystis. CONCLUSION: These findings suggest that hypoplasia of the
      abdominal musculature and cryptorchidism might develop secondary to the presence
      of chronic megalocystis in this syndrome.

PMID- 8159381
TI  - Neonatal cushingoid syndrome resulting from serial courses of antenatal
      betamethasone.
AB  - BACKGROUND: Antenatal steroid therapy has been shown to induce accelerated
      pulmonary maturation in preterm fetuses when delivery is imminent. Although this
      form of therapy has been used for 20 years, few studies or case reports have
      discussed the indications for or complications of retreatment, especially when
      more than two courses of steroids have already been given. We report a case of
      neonatal cushingoid syndrome with hypothalamic-pituitary-adrenal axis suppression
      following maternal treatment with seven courses of betamethasone. CASE: A 31-year
      old white woman, gravida 3, para 1, spontaneous abortion 1, presented with a
      single intrauterine pregnancy at 24 weeks' gestation, a bulging amniotic sac, and
      repeated cerclage failure. Antenatal betamethasone therapy was begun at 12.5 mg
      intramuscularly every 12 hours for two doses. Because of cervical dilatation,
      bulging membranes, and intermittent contractions, the expectation of imminent
      premature delivery did not diminish over the next 42 days. As the effect of
      antenatal steroids wanes after 7 days, a course of therapy was administered each
      week for as long as the threat of preterm delivery remained. Seven courses of
      betamethasone were given before delivery at 34.5 weeks post-conception age. The
      2625-g male neonate appeared cushingoid on physical examination, with basal serum
      cortisol levels less than 3.3 micrograms/dL. CONCLUSION: Physical findings of the
      neonate and laboratory investigation of both infant and mother suggested combined
      hypothalamic-pituitary-adrenal axis suppression. The cushingoid features of the
      infant demonstrate an undesired and previously unreported complication of an
      effective antenatal therapy. The unusual variant in this case was that the
      initial indication for steroid therapy (risk of premature delivery) persisted for
      8 weeks after the first dose of betamethasone. It remains unknown how many weekly
      antenatal steroid courses can be administered before marked fetal adrenal
      suppression becomes evident. Risk-benefit ratios should be carefully considered
      before each retreatment.

PMID- 8159382
TI  - Amnioinfusions in renal agenesis.
AB  - BACKGROUND: Renal agenesis causes severe oligohydramnios, which results in
      compression effects, lung hypoplasia, and rapid neonatal death. CASE: We report a
      case of renal agenesis identified in a fetus in which serial amnioinfusions were
      employed to prevent pulmonary hypoplasia and compression effects. A total of ten
      amnioinfusions were performed between 17-33 weeks' gestation. Chorioamnionitis
      led to preterm delivery at 33 weeks. The infant had no significant pulmonary
      hypoplasia and none of the compression effects usually associated with the
      oligohydramnios sequence. Peritoneal dialysis was provided for the infant with a
      long-term aim of eventual renal replacement therapy, but dialysis was
      unsuccessful and the infant died at the age of 23 days. Autopsy revealed slightly
      small lungs and extensive cavitating lesions in the brain, which were presumed to
      be of peripartum or antenatal origin. The chain of events leading to this unusual
      course of action is described, and the ethical aspects are outlined. CONCLUSION:
      At present, this type of procedure is not an appropriate intervention in cases of
      renal agenesis, and such management is strongly discouraged.

PMID- 8159384
TI  - Conservative management of an ovarian polyembryoma.
AB  - BACKGROUND: Polyembryomas are rare, immature germ cell malignancies characterized
      by numerous embryo-like bodies in association with mature and immature teratoma
      structures and primitive embryonic tissue. The purpose of this paper is to
      present a patient in whom surgical staging and postoperative serial tumor markers
      and imaging studies were used to determine management. CASE: A 43-year-old woman
      with a stage IA polyembryoma was followed with serial alpha-fetoprotein and hCG
      assays, as well as serial abdominal and pelvic computed tomography (CT) scans,
      following surgical staging and a total abdominal hysterectomy and bilateral
      salpingo-oophorectomy. Chemotherapy was not given because the patient's tumor
      markers declined steadily into the normal range and imaging studies revealed no
      evidence of recurrent disease. CONCLUSION: Women with polyembryomas surgically
      staged and confined to one ovary may be followed with serial tumor markers and
      diagnostic imaging techniques to avoid aggressive cytotoxic chemotherapy.

PMID- 8159383
TI  - Prolapse of the sigmoid neovagina: report of three cases.
AB  - BACKGROUND: Prolapse of a sigmoid neovagina, created in patients with congenital
      vaginal aplasia or male transsexualism, is rare. In correcting this condition,
      preservation of coital function and restoration of the vaginal axis should be of
      primary interest. CASES: One patient with Mayer-Rokitansky-Kuster syndrome
      developed a protrusion of the sigmoid neovagina almost 4 years after the initial
      operation. The prolapse was treated successfully using an abdominal approach to
      suspend the neovagina to a Cooper ligament. The second patient is a male-to
      female transsexual who developed a prolapse 3 years after the creation of a
      sigmoid neovagina. After suspension of the neovagina to a Cooper ligament, the
      prolapse recurred; in a repeat approach, the neovagina was successfully suspended
      to the sacral promontory. The third patient, with Mayer-Rokitansky-Kuster
      syndrome, complained of a protrusion immediately after creation of the neovagina.
      Initially, the redundant sigmoid was resected vaginally. However, the prolapse
      recurred, and an abdominal suspension to a Cooper ligament was performed.
      Finally, after 1 year, another recurrence was treated successfully with a vaginal
      approach. CONCLUSION: Prolapse of an artificially created vagina is a rare
      occurrence, without a standard treatment. Both abdominal and vaginal approaches
      may be needed to restore the neovagina without compromising its function.

PMID- 8159385
TI  - Chyloperitoneum following treatment for advanced gynecologic malignancies.
AB  - BACKGROUND: Chyloperitoneum is an uncommon complication following retroperitoneal
      surgery. Blunt abdominal trauma, abdominal surgery, abdominal or pelvic
      radiation, cirrhosis, lymphoma, tuberculosis, and congenital defects of lacteal
      formation may also lead to chylous ascites. CASES: Two patients developed chylous
      ascites after treatment for gynecologic malignancies. One, who also received
      pelvic and abdominal radiation, developed chylous ascites 11 months after
      retroperitoneal lymph node dissection for advanced endometrial cancer. She was
      treated with a diet low in fat and high in medium-chain triglycerides, as well as
      with intravenous hyperalimentation. She had recurrences of chylous ascites, which
      responded to paracentesis and intravenous hyperalimentation. The second patient
      developed chylous ascites 2 months after retroperitoneal lymph node dissection
      for advanced fallopian tube cancer. She was treated with a medium-chain
      triglyceride diet, which resulted in resolution of her symptoms. CONCLUSION:
      Chyloperitoneum is an uncommon complication following treatment for gynecologic
      malignancies. Our second case is the first reported in which retroperitoneal
      lymph node dissection for gynecologic malignancy resulted in chyloperitoneum.
      However, because gynecologic malignancies frequently metastasize to the
      periaortic lymph nodes, chylous ascites may be an important cause of morbidity
      following treatment.

PMID- 8159386
TI  - Primary hypothyroidism associated with multicystic ovaries and ovarian torsion in
      an adult.
AB  - BACKGROUND: Primary hypothyroidism is known to be associated with multicystic
      ovaries in juvenile females, but this association has been reported only once
      previously in an adult. This report describes an unusual case of bilateral
      multicystic ovaries occurring in an adult patient with profound hypothyroidism.
      CASE: A 26-year-old woman presented with an acute abdomen and bilateral adnexal
      masses. An emergency exploratory laparotomy revealed bilateral enlarged
      multicystic ovaries with torsion of the right ovary. Because this ovary was
      necrotic, it was removed; pathology revealed multiple hemorrhagic follicular
      cysts. Laboratory studies to evaluate the cause of the multicystic ovaries
      revealed negative serum beta-hCG, LH 0.7 IU/L, FSH 15.7 IU/L, and estradiol 80
      pg/mL. The TSH value was greater than 50 IU/L and serum thyroxine was
      undetectable, demonstrating profound hypothyroidism. Subsequent thyroid hormone
      replacement was associated with resolution of the cysts in the remaining ovary.
      CONCLUSION: Profound hypothyroidism can cause multicystic ovaries in an adult. In
      the absence of ovarian torsion, surgery can be avoided, as thyroid hormone
      replacement leads to clinical resolution of the cysts within 3 months.

PMID- 8159387
TI  - Torulopsis glabrata pelvic abscess and fungemia.
AB  - BACKGROUND: Serious infections caused by Torulopsis glabrata, once rarely
      encountered, have become common over the last 3 decades. The most frequent
      manifestations of serious fungal infections include septicemia, endocarditis,
      hepatosplenic infections, and meningitis. We report a case of fungemia and pelvic
      abscess caused by T glabrata following gynecologic surgery. CASE: A 43-year-old
      woman developed fever, abdominal pain, and abdominal distention following a total
      abdominal hysterectomy and right salpingo-oophorectomy. Empirical treatment with
      broad-spectrum antimicrobial agents was not successful. Three sets of blood
      cultures were positive for T glabrata, and radiologic investigations revealed
      pelvic and lesser sac fluid collections. Cultures of the pelvic abscess grew T
      glabrata. Treatment was changed to amphotericin B, with complete clinical
      recovery. CONCLUSION: Serious T glabrata infections are rare following
      gynecologic surgery, especially in immunocompetent patients. Given the morbidity
      and mortality associated with these infections, aggressive treatment with
      amphotericin B and drainage of abscesses is warranted.

PMID- 8159388
TI  - Pelvic granulomata mimicking endometriosis following the administration of oil
      based contrast media for hysterosalpingography.
AB  - BACKGROUND: Hysterosalpingography is used commonly in the evaluation of
      infertility and in the diagnosis of anomalies of the uterus and fallopian tubes.
      There is continued debate over the safety and diagnostic or therapeutic efficacy
      of water-soluble versus oil-based contrast media. CASE: A 29-year-old woman with
      secondary infertility underwent hysterosalpingography with both water-soluble and
      oil-based contrast. The fallopian tubes appeared normal. Six months later, a
      plain abdominal radiograph obtained at the occasion of a minor motor vehicle
      accident revealed evidence of retained loculated pelvic contrast material.
      Subsequent laparoscopy identified adhesions and cul-de-sac implants strongly
      suspicious for endometriosis. Biopsy and pathologic study documented
      lipogranuloma. CONCLUSION: Oil-based contrast media instilled into the pelvis at
      hysterosalpingography can persist for prolonged periods and create granulomatous
      lesions mimicking endometriosis. In view of the controversy whether oil-based
      contrast materials are superior to water-soluble media, the routine use of oil
      based contrast media should be considered carefully.

PMID- 8159389
TI  - Transcatheter embolotherapy for the treatment of pelvic congestion syndrome.
AB  - BACKGROUND: Both medical and surgical treatments have been used for pelvic
      congestion syndrome. An analogous condition in males, varicocele testis, has been
      treated successfully for many years by transcatheter embolotherapy. CASES: We
      performed percutaneous transcatheter embolization of the ovarian veins in three
      women with chronic pelvic pain and venographically demonstrated pelvic venous
      congestion. In all three cases, the ovarian veins were embolized bilaterally from
      the femoral approach, using stainless-steel coils. After the treatment, all
      subjects experienced a dramatic decrease in pelvic pain, as well as an
      improvement in two or more preexisting symptoms, including extremity swelling,
      dyspareunia, external varicosities, constipation, and emotional disturbance. One
      patient's symptoms recurred at 1.2 years and required surgery; the other two
      continue to have long-term benefit. CONCLUSION: These findings suggest that
      pelvic venous congestion was the likely etiologic factor in pelvic pain
      experienced by these women and that transcatheter ovarian vein embolotherapy may
      be an effective treatment for such a condition.

PMID- 8159390
TI  - An unusual late presentation of imperforate hymen.
AB  - BACKGROUND: The imperforate hymen is a rare gynecologic abnormality that may not
      be detected until the onset of menses, when hematocolpos causes symptoms due to
      an expanding pelvic mass. CASE: A 19-year-old woman had primary amenorrhea,
      originally misdiagnosed as mullerian agenesis. Because of a combination of late
      onset of menses, vaginal dilation, and sexual intercourse, her hematocolpos
      remained relatively asymptomatic. CONCLUSION: Proper diagnosis of the imperforate
      hymen could have been made earlier by contrasting the ultrasound findings with
      the absence of associated genitourinary and skeletal anomalies. Magnetic
      resonance imaging can detect a uterus not previously seen on ultrasound. An early
      imaging study may further prevent the misdiagnosis of congenital absence of the
      uterus.

PMID- 8159391
TI  - Laparoscopic repair of a vesicovaginal fistula: a case report.
AB  - BACKGROUND: Operative laparoscopy was performed for the management of ovarian
      remnant syndrome involving the bladder, bowel, vagina, and ureters, and requiring
      extensive dissection. A vesicovaginal fistula developed postoperatively. CASE:
      Because of the complexity and location of the fistula, a vaginal approach was not
      appropriate. Using techniques of videolaparoscopy, videocystoscopy, and operative
      laparoscopy, the fistula was repaired. CONCLUSION: In experienced hands,
      endoscopic management of complex vesicovaginal fistulas may be an alternative to
      the traditional abdominal approach.

PMID- 8159392
TI  - Outcome of pregnancy after laparoscopy and chromotubation during cycles of
      conception: a report of three cases.
AB  - BACKGROUND: Diagnostic tubal patency procedures may displace an early pregnancy.
      Hysterosalpingography performed in the presence of an unrecognized pregnancy has
      been reported to result in an ectopic pregnancy. No such information on
      laparoscopy performed during a cycle of conception has been reported. CASES:
      Three cases of laparoscopy were performed during the luteal phase of an
      unrecognized pregnancy cycle. The three patients were counseled to avoid
      conception before surgery. All had an undetectable serum hCG level within 3 days
      of surgery and an undetectable urine hCG level on the day of surgery. The three
      pregnancies had an uneventful prenatal course, with delivery at term. CONCLUSION:
      Although follicular phase scheduling of tubal patency tests would avoid potential
      pregnancy complications, the risk from luteal phase laparoscopy and
      chromotubation to an unrecognized pregnancy may be less than expected.

PMID- 8159393
TI  - The role of patient history in the diagnosis of urinary incontinence.
AB  - OBJECTIVE: To assess the clinical usefulness and validity of patient history in
      the diagnosis of genuine stress incontinence and detrusor overactivity. DATA
      SOURCES: A literature search was performed for publications addressing the
      clinical evaluation of urinary incontinence between 1975-1992. METHODS OF STUDY
      SELECTION: Nineteen of 29 articles during this period reported data in such a
      manner as to allow statistical comparison of patient history to the diagnosis
      based on urodynamic evaluation. DATA EXTRACTION AND SYNTHESIS: Each article was
      assessed for the following information: inclusion and exclusion criteria, method
      of obtaining patient history, clinical evaluation, and diagnostic criteria.
      Patients in each article were classified according to their history and
      urodynamic diagnosis. Sensitivity, specificity, and predictive values were
      calculated for each article, as well as for the combined data from all articles.
      Combined data from all 19 articles produced a total of 3092 and 2950 patients
      evaluated for genuine stress incontinence and detrusor overactivity,
      respectively. A clinical history consistent with stress incontinence, when
      compared to a urodynamically based diagnosis, showed a sensitivity of 0.906, a
      specificity of 0.511, a positive predictive value of 0.749, and a negative
      predictive value of 0.771. A comparison of clinical history suggestive of an
      overactive detrusor and urodynamic evidence of spontaneous bladder activity
      revealed a sensitivity of 0.735, specificity of 0.552, positive predictive value
      of 0.561, and negative predictive value of 0.728. CONCLUSION: Patient history
      alone is not an accurate tool in the diagnosis of genuine stress incontinence or
      detrusor overactivity, and should not be the sole determinant of diagnosis or
      treatment.

PMID- 8159394
TI  - The pendulum has swung too far. Bracing for adolescent idiopathic scoliosis in
      the 1990s.
AB  - During the past 10 years, the brace treatment of adolescent idiopathic scoliosis
      has been highly controversial. In the 1960s, brace treatment was pursued
      enthusiastically; whereas in the 1980s, brace treatment was received negatively.
      As is typical in most of medicine, when such opposing philosophies exist, the
      truth lies somewhere in between. This article describes the middle ground, the
      place brace treatment now stands, in the 1990s.

PMID- 8159395
TI  - Outcomes analysis in spinal research. How clinical research differs from outcomes
      analysis.
AB  - This article discusses the outcomes research movement and makes a distinction
      between clinical research that includes measures of function and quality of life
      as variables, and outcomes measurement for operational purposes such as quality
      assurance and reporting to insurers and regulatory agencies. Suggestions are made
      about how to begin outcomes data collection in an orthopedic clinic setting and
      how to select which patient outcomes may be most relevant to the assessment of
      treatment for spinal deformities.

PMID- 8159396
TI  - Common sense in the management of adolescent idiopathic scoliosis.
AB  - The 25-year experience of Santa Casa Spine Center in treating patients with
      adolescent idiopathic scoliosis is reported. The orthotic and surgical treatments
      and their complications are discussed, showing efficient, cost-effective ways of
      acting on these disorders in countries that lack more expensive and modern
      instrumentation.

PMID- 8159397
TI  - Analysis and treatment of type II idiopathic scoliosis.
AB  - The evaluation and management of scoliosis curves depend on careful study and
      curve classification. This article discusses current concepts of curve
      classifications and analyzes Type II curves in particular in hopes of making it
      easier to manage these curves from both nonoperative and operative standpoints.

PMID- 8159398
TI  - Preoperative assessment of the child with neuromuscular scoliosis.
AB  - The medical preoperative assessment of the child with neuromuscular scoliosis
      under consideration for spinal fusion is presented. Issues of the respiratory,
      gastrointestinal, cardiovascular, and hematologic systems as well as nutrition
      are reviewed. An outline of preoperative screening tests and a discussion of
      common medical issues should help the surgeon prepare the child with
      neuromuscular scoliosis for spinal reconstructive surgery.

PMID- 8159399
TI  - Imaging evaluation of patients with spinal deformity.
AB  - CT myelography and MRI provide the best means of preoperatively assessing
      patients with spinal deformities. Owing to its noninvasive nature and its
      superior soft-tissue contrast, MRI represents the single best modality in the
      evaluation of a patient with any deformity. MRI allows complete preoperative
      surgical planning and obviates the need for any additional studies. Screening of
      the entire cord in a patient with a deformity is best accomplished with sagittal
      and coronal (as needed) T1W images. These images allow assessment of the cord for
      compression, tethering, syrinx, enlargement, and Arnold-Chiari malformation.
      Evaluation of cord compression at the apex of a curve is the single most
      important consideration other than the diagnosis of intrinsic cord abnormality.
      Subsequent sagittal or axial T2W images may be helpful if specific abnormalities
      are noted on T1W screening images. Coronal images are particularly helpful in
      patients with prominent curves or in those with vertebral anomalies.
      Additionally, coronal images may be useful in assessing patients with suspected
      diastematomyelia. Advances in hardware and software design have resulted in
      marked improvements in the ability to satisfactorily image all aspects of
      patients with spinal deformities. New phased array coils allow rapid imaging of
      larger portions of the spine. For instance, a complete MRI of the spine can be
      performed in a child in the same length of time that would have been necessary
      for a single lumbar examination when MRI was in it's infancy. The use of fast
      spin-echo imaging also permits more rapid acquisition times. CT myelography
      remains useful for those patients who cannot undergo MRI or for those with
      specific abnormalities such as multilevel central spinal stenosis when dynamic
      information obtained during the myelogram might be helpful. CT myelography
      represents the only means of assessing the central spinal canal of patients with
      metallic instrumentation in place. With the exception of these limited
      applications, MRI has replaced CT myelography as the imaging study of choice in
      the evaluation and examination of patients with spinal deformities.

PMID- 8159400
TI  - The role of discography in the evaluation of patients with spinal deformity.
AB  - The indications, applications, and technique of lumbar, thoracic, and cervical
      discography in patients with spine deformity are presented. Details of technique
      for each anatomic region are provided, along with representative case
      presentations. The role of discography in the assessment of juvenile discogenic
      disease in association with spinal deformity (Scheuermann's disease) in the
      thoracic and lumbar regions also is discussed.

PMID- 8159401
TI  - Surgical treatment of idiopathic thoracolumbar and lumbar scoliosis in adolescent
      patients.
AB  - The surgical management of idiopathic thoracolumbar and lumbar scoliosis is
      complex because of the surgeon's desire to achieve curve correction while
      maintaining normal lumbar lordosis with as many distal mobile lumbar segments as
      possible. By doing so, the surgeon is able to maintain normal sagittal alignment
      and decrease the chance of degenerative lumbar spine disease below the scoliosis
      fusion. This article discusses the surgical treatment of the thoracolumbar and
      lumbar curve, and, it is hoped, provides a better understanding of this complex
      problem.

PMID- 8159402
TI  - Techniques of instrumentation in long fusions to the sacrum.
AB  - Arthrodesis of long segments of the spine to a sacrum may be necessary for a
      variety of pathologic conditions and indications. The surgery may be necessary
      for patients who have had prior surgery, had failure of fusion, or had
      degeneration above the area of prior fusion. Revision of prior surgeries, in
      which distraction instrumentation was used and resulted in flat-back deformity,
      remains a problem. A better understanding of the biomechanical stresses placed on
      the fixation devices and the bone-implant interface have resulted in development
      of improved techniques of fixation in the lower lumbar spine and the sacrum. This
      fixation always requires multiple levels of segmental spinal purchase. The type
      of purchase obtained is dependent on the design of the fixation, whether it is
      wire, hook, or screw, and the bone into which it is placed. The surgeon needs to
      understand the limitations of both the instrumentation and bone prior to
      proceeding with this demanding surgery. When so much emphasis is placed on
      instrumentation, a tendency exists to not pay enough attention to the most
      important part of the operation. This surgery is always an arthrodesis and an
      attempt to place the spine in a stable and balanced position. Meticulous surgical
      techniques for arthrodesis are required, or failure is likely to occur. If the
      spine is placed in an unbalanced situation and the fusion area is placed under
      tension, failure of fusion and, subsequently, of the instrumentation will occur.
      The understanding of these concepts and principles is more critical to the
      success of this type of surgery than the specific instrumentation used.
      Instrumentation will continue to change using different metallurgy and designs,
      but these principles and the goal of obtaining a solid arthrodesis and a balanced
      spine will never change.

PMID- 8159403
TI  - Congenital scoliosis of the cervical or cervicothoracic spine.
AB  - Congenital cervical or cervicothoracic scoliosis is an unusual but potentially
      severe disfiguring cause of spinal deformity in the growing child and adolescent.
      These forms of scoliosis are among the most infrequently encountered, and
      therefore, relatively little literature is available to guide the orthopedic
      surgeon. This article presents a brief overview of the etiology and epidemiology
      of these rare forms of scoliosis, defines the pathoanatomic variants, reviews the
      nonoperative treatment methods available, and discusses the role of early
      recognition and recommendation for spinal arthrodesis of those curves that
      clearly need surgical stabilization.

PMID- 8159404
TI  - The Galveston technique using Luque or Cotrel-Dubousset rods.
AB  - The Galveston technique for pelvic fixation in long fusions to the sacrum in
      neuromuscular and adult scoliosis is an effective technique to help obtain a
      solid fusion. With careful technique and accurate rod bending, rod insertion, rod
      contouring, and wire tightening, excellent fixation is obtained that maximizes
      the fusion rate.

PMID- 8159405
TI  - The Lea-Plaza frame for scoliosis.
AB  - Excellent correction of the scoliotic deformity in the three space planes is
      planes is obtained with the use of the Lea-Plaza frame. This article discusses
      the indications and contraindications, surgical technique, results, and
      complications of this technique.

PMID- 8159406
TI  - Harrington instrumentation without arthrodesis and consecutive distraction
      program for young children with severe spinal deformities. Experience and
      technical details.
AB  - The treatment of severe spinal deformities in childhood is a great challenge. The
      nonoperative treatment is not always successful, and correction with spinal
      fusion is not usually the most desirable goal because it may result in a
      straighter but shorter trunk. Spinal instrumentation without arthrodesis is an
      alternative to these difficult decisions that allows child growth with control of
      the deformity. At the same time that there is considerable improvement in the
      natural history of these deformities, this treatment presents great morbidity.
      The combination of Harrington instrumentation and consecutive distractions is a
      difficult program but it has been the best answer for these complicated patients
      up to now.

PMID- 8159407
TI  - The King V curve pattern. Its analysis and surgical treatment.
AB  - The importance of the double thoracic (King V) curve lies in the need for the
      patient to have a balanced connection. None of us wishes to produce a
      decompensated trunk patient as the result of our surgical efforts. To recognize
      the curve pattern, one should read carefully the classic article by King et al.
      To select the proper technique of management, one should read the new work by Lee
      et al, which discusses subtleties not described in the previous article. At our
      center, we favor balanced correction so that the result is two curves of equal
      value, level shoulders, absence of an ugly trapezius area prominence, a vertical
      and well-centered torso, and a normal sagittal contour. Over-correction of the
      right thoracic curve must be avoided.

PMID- 8159408
TI  - [Reducing low density lipoprotein-cholesterol levels by apheresis].
AB  - The predominate number of homozygote familial hypercholesterolemic and
      approximately 20% of heterozygotes are resistant to low cholesterol diet and
      lipid lowering pharmacological treatment even in combination of 2 or more drugs.
      In such cases, the selective lipoprotein apheresis has become a promising
      alternative and indicated absolute (homozygotes) or relative (heterozygotes). The
      combination of low density lipoprotein apheresis, together with diet and drugs,
      should allow a maximal lowering of low density lipoprotein-cholesterol (-60-70%).
      Besides low density lipoprotein, various apheresis procedures may also eliminate
      other potentially atherogenic factors, such as lipoprotein(a) and fibrinogen and
      acutely improve the haemo-rheological status of the patient. The authors review
      several lipoprotein apheresis procedures with varying degrees of selectivity,
      those have and furthermore analysis the advantages and disadvantages and cost of
      each procedure.

PMID- 8159409
TI  - [Correlation between long survival and shunt patency in patients treated
      surgically for refractory ascites].
AB  - The survival data of 31 patients operated on for refractory ascites in the 7-year
      long period between 1983 and 1989 have been analysed in relation to the patency
      of the shunt. In the follow-up examination of the 7 patients who had survived 3
      years flow-through contrast material was used and the patency of the shunt was
      documented by percutaneous injection of the contrast material under X-ray. The
      authors search for explanation in cases where the shunt was non-conducting
      (blocked) in ascites-free patients. No considerable difference was found between
      the two long survival assuring types of the shunt (LeVeen and Denver). 55% out of
      the 31 patients operated on had survived 2 years and almost 30% had survived 3
      years.

PMID- 8159410
TI  - [Intraoperative evaluation of the function of the saphenous vein as coronary
      graft, visualized by myocardial contrast echocardiography].
AB  - The assessment of area at risk of saphenous vein graft occlusion is an unsolved
      problem. We studied myocardial perfusion with contrast echocardiography in 13
      patients undergoing coronary surgery. The left ventricle was imaged in the
      transgastric short axis view at midpapillary muscle level. The myocardial
      distribution area of 21 saphenous vein grafts was measured by injecting 0.2-0.5
      cc of sonicated 5% albumin microspheres directly in the graft, early after
      weaning from cardiopulmonary bypass. Percent left ventricular area opacification
      was calculated for each graft injection: right coronary (N = 8) 21 +/- 7%,
      marginal branch (N = 10) 17 +/- 5%, left anterior descending and diagonal branch
      (N = 3) 41 +/- 4%. Myocardial systolic wall thickening was not effected by
      contrast injection (preinjection 45 +/- 12% vs postinjection 46 +/- 7%, p = NS).
      No local or systemic side effects were encountered. IN CONCLUSION: myocardial
      contrast echocardiography is a safe and useful method to measure the area at risk
      for saphenous vein graft occlusion.

PMID- 8159411
TI  - [Anaplastic transformation of papillary carcinoma of the thyroid].
AB  - Anaplastic transformation of well-differentiated carcinomas of the thyroid is not
      common. The authors present a case of a 61-year-old woman, on whom, 17 years
      earlier, a near-total thyroidectomy was performed with a unilateral selective
      lymphatic dissection of the neck because of a papillary carcinoma of the thyroid.
      The operations were followed by a course of external irradiation. For 17 years
      the patient had no complaints, then she was treated again for recurrence of tumor
      in the residual thyroid tissue. By biopsy next to papillary carcinoma the authors
      diagnosed an anaplastic tumor with giant cells, which led to the patient's death
      6 months after the operation. Surveying the data in literature they draw
      attention to the role of external irradiation in anaplastic transformations after
      the first operation.

PMID- 8159412
TI  - [Complex eldercare in a Budapest district].

PMID- 8159413
TI  - [Methodical and practical reliability of natural family planning].

PMID- 8159414
TI  - [The problem of obtaining virus-free blood products].

PMID- 8159415
TI  - Soft-tissue augmentation and replacement in the head and neck. General
      considerations.
AB  - It is clear that many of the factors that affect wound healing when natural
      biomaterials are used also affect the long-term success of semisynthetic and
      synthetic alloplasts. The development of a new generation of biomaterials that
      combine synthetic components with bioactive proteins are just now beginning to
      move from the laboratory into clinical testing. Within the next decade,
      biologically active growth proteins, in combination with resorbable synthetic
      alloplasts, may allow missing tissues to be regenerated rather than just "filled
      in" by permanent implants. There will also be a steady drift away from materials
      that show any risk of being carcinogenic or immunoreactive over time. As
      promising as these new alloplasts appear to be, we should learn from past
      experience. Implants that initially seem biocompatible can fail in unpredictable
      ways when exposed to the hostile environment of the body. As surgeons, we well
      ultimately be held responsible for the biomaterials we implant. Our selection of
      biomaterials should be based on sound scientific and surgical knowledge, and not
      solely upon the recommendations of manufacturers. The authors hope that the
      information in this monograph will help to integrate reconstructive options so
      that autologous tissues are used whenever possible and synthetic materials are
      appropriately selected and applied when necessary.

PMID- 8159416
TI  - Nerve grafting and neuromuscular transfers.
AB  - In today's otolaryngology practice, surgeons frequently encounter situations in
      which soft-tissue augmentation is needed. Traditionally, fat, fascia, and
      nonvascularized muscle have been used for these purposes. This article reviews
      the history as well as the current applications and limitations of these
      materials. Although not ideal in all circumstances, these materials remain useful
      in selected situations.

PMID- 8159417
TI  - The wound healing response to grafted tissues.
AB  - When a tissue graft is introduced into a healing wound, the inflammatory and
      proliferative stages of wound healing are significantly prolonged. This sustained
      stimulation at the surrounding graft site can develop into chronic inflammation,
      leading to fibrosis and connective tissue build-up around the graft. Persistence
      in chronic inflammation surrounding a tissue graft can lead to graft destruction
      or rejection. Thus, a basic understanding of soft-tissue wound healing in
      response to grafted tissue is important to optimize the long-term functional
      results of tissue grafts.

PMID- 8159418
TI  - Local cutaneous flaps.

PMID- 8159419
TI  - Muscular and myocutaneous pedicled flaps.
AB  - This article reviews the major regional myocutaneous flaps available for soft
      tissue coverage in the head and neck region. Specific flaps discussed include the
      pectoralis myocutaneous, latissimus dorsi myocutaneous, trapezius myocutaneous,
      sternocleidomastoid muscle, and temporalis muscle flaps.

PMID- 8159420
TI  - Soft-tissue microvascular free flaps.
AB  - Microvascular free flaps have revolutionized the reconstruction of soft-tissue
      defects in the head and neck region in the last decade. In this article, the
      anatomy, surgical techniques, advantages, and disadvantages of a variety of flaps
      are discussed.

PMID- 8159421
TI  - Soft-tissue response to synthetic biomaterials.
AB  - The soft-tissue response to an implanted synthetic material is an inflammatory
      reaction to foreign body; factors that minimize this inflammation will maximize
      biocompatibility. The ideal implant is selected from a material that is non
      toxic, nonantigenic and in chemical proximity to calcium or carbon on the
      periodic table. If it is porous, the pores should be large enough to admit immune
      and phagocytic cells and ideally, to allow native tissue ingrowth. The implant
      should be of appropriate size and shape and should be implanted in the correct
      location. The material should be nonparticulate, should resist fragmentation, and
      should be secured in the selected location after gentle insertion. All these
      factors help decrease the body's natural response to an implanted foreign body,
      but inflammation and foreign body reaction are the common threads in all
      responses to all implanted synthetic materials. Optimum soft-tissue
      biocompatibility, characterized either by thin fibrous encapsulation or by
      mesenchymal ingrowth into pores and interstices, is achieved by avoiding or
      containing this response.

PMID- 8159422
TI  - Surgical tissue adhesives in otolaryngology-head and neck surgery.
AB  - The primary surgical tissue adhesives used in otolaryngology-head and neck
      surgery include the cyanoacrylate derivatives and the fibrin tissue adhesives.
      The cyanoacrylate derivatives are effective for superficial skin closure. Use of
      this material below the level of the skin can result in acute and chronic
      inflammation and tissue necrosis. Fibrin tissue adhesives can be used for wound
      closure, tissue sealing, and hemostasis. Drawbacks noted with the fibrin tissue
      adhesives include method of preparation, relatively low binding strength, and
      variable resorption time. This article discusses the properties, methods of
      preparation, and clinical indications of the cyanoacrylate derivatives and fibrin
      tissue adhesives.

PMID- 8159423
TI  - Injectable filler materials for soft-tissue augmentation.
AB  - The concept of non-surgical implantation of injectable filler materials for soft
      tissue augmentation has always been an attractive option for the head and neck
      surgeon. The ideal injectable soft tissue filler material would be easy to use,
      biocompatible, nontoxic, and long-lasting. Presently available filler materials
      present significant drawbacks to their use. The most favorable filler materials
      appear to be autologous fat and microparticulate alloplasts. This article reviews
      presently used injectable filler materials and those that may be used in the
      future.

PMID- 8159424
TI  - Synthetic biomaterials for soft-tissue augmentation and replacement in the head
      and neck.
AB  - Within the next 10 to 15 years, synthetic biomaterials will probably become
      available that may make many of the polymeric implants discussed in this article
      obsolete. These new, genetically engineered biomaterials will contain morphogenic
      proteins capable of directing new tissue growth. We may be able to engage in true
      "tissue engineering" that allows us to grow a number of tissue types at will, as
      opposed to implanting bioinert compounds that only mimic the shape of living
      tissue. Regardless of whether the promise of genetically engineered growth
      proteins is ever realized, there will be a steady move away from polymeric
      implant materials that show even the hint of being able to cause cancer or an
      immune reaction. This movement will result primarily from liability pressure
      rather than scientific or medical indications. Polymeric biomaterials that are
      generally regarded as safe now may not be considered safe in the future. The
      surgeon who implants a biomaterial now may have to deal with a malpractice
      situation many years after the implant was placed. This is exactly the situation
      now faced by general plastic surgeons who have used silicone gel breast implants.
      It is wise, then, to limit the use of these polymer implants in terms of the
      number implanted and types used. If autogenous tissue is available and will
      adequately solve the problem, it should be used preferentially. If this is not
      possible, the surgeon should select only those implants with the lowest potential
      for future immunologic problems, carcinogenicity, and polymeric degradation over
      time.

PMID- 8159425
TI  - Skin grafts.
AB  - In this article, we have reviewed important issues regarding skin graft
      reconstruction of cutaneous and mucosal defects in the head and neck. Careful
      attention to surgical technique and immobilization of the grafts during healing
      lead to more successful reconstructions. Partial-thickness skin grafts lack
      epidermal appendages. When used for cutaneous reconstruction, they must be
      protected from desiccation and excessive trauma. Donor site morbidity can be
      reduced by protection against environmental trauma and excessive sunlight.

PMID- 8159426
TI  - Bone and cartilage reconstruction with tissue engineering approaches.
AB  - Tissues can be engineered to create new cartilage, bone, or bone-cartilage
      composites using synthetic polymer scaffolding as cell anchorage sites on which
      cells are transplanted. Topics discussed in this article include cell culture,
      material sciences, cell transplantation, tissue engineering, and clinical
      applications.

PMID- 8159427
TI  - The use of autogenous fat, fascia, and nonvascularized muscle grafts in the head
      and neck.
AB  - We have reviewed the transplantation of autogenous fat, fascia, and
      nonvascularized muscle. Although none of these tissues satisfies all of the
      requirements for an ideal transplantation material, understanding the indications
      and each material's limitations will broaden the surgeon's armamentarium when
      soft-tissue grafting is desired. Although the use of autogenous fat grafts in
      head and neck surgery has been associated with some unpredictability, fat remains
      an excellent choice for obliteration of frontal sinuses, for myringoplasty, and
      for limited soft-tissue augmentation. In most applications, significant
      resorption of the transplanted fat can be expected, and it should be compensated
      for accordingly by initial overcorrection. Future research endeavors, including
      development of preadipocyte transplants and hormonal manipulation of fat grafts,
      will perhaps improve results of transplantation. The grafting of fascia has been
      shown to be a very reliable technique, especially when tensile strength is
      required of the transplant material. In grafts, fascia is much more predictable
      than fat, in that the majority of the fascia survives as living tissue that
      retains its original characteristics. A relative lack of three-dimensional bulk,
      however, limits the use of fascia in soft-tissue augmentation. The
      transplantation of nonvascularized muscle, because of its enormous metabolic
      requirements, almost always results in death of the muscle cells and subsequent
      partial replacement by fibrous tissue. Free muscle grafts therefore have very
      limited application, except in circumstances in which fibrous tissue obliteration
      of small defects (such as the nasofrontal duct or eustachian tube) is the desired
      result. In clinical situations in which maintenance of the substance or bulk of
      the transplanted material is of paramount importance, consideration should be
      given instead to the transfer of vascularized tissue. For this purpose, numerous
      simple and composite flaps of fascia, fat, muscle, and other tissues are now
      available. Vascularized tissue transfers are certainly not the solution to every
      reconstructive problem, however. When properly selected and applied, the
      transplantation of fat, fascia, and occasionally muscle remains an important
      option for soft-tissue replacement in head and neck surgery.

PMID- 8159428
TI  - Cartilage grafts for head and neck augmentation and reconstruction. Autografts
      and homografts.
AB  - This article reviews cartilage grafting in the head and neck, emphasizing its use
      in facial surgery. The harvesting and preparation of cartilage grafts are
      reviewed, and both autografts and homografts are discussed. The implementation of
      cartilage grafts in the nose, ear, eyelid, orbit, and larynx also is presented.

PMID- 8159429
TI  - Free composite grafts.

PMID- 8159431
TI  - Workers' compensation reform--what it means to you.

PMID- 8159430
TI  - Vascular grafts in head and neck reconstructive surgery.
AB  - The best management of advanced head and neck tumors invading the carotid artery
      utilizes a collaborative, anticipatory approach. Preoperative characterization of
      the anatomy and extent of tumor involvement, coupled with the physiologic
      assessment of the cerebrovascular circulation through the variety of adjunctive
      studies, facilitates operative planning. Careful preoperative evaluation allows
      the surgeon to make the most informed decision regarding extracranial carotid
      artery reconstruction, should carotid artery resection be required for adequate
      tumor removal. When the preoperative evaluation indicates that adequate cerebral
      perfusion or collateral reserve will not be maintained with carotid artery
      occlusion, carotid artery reconstruction needs to accompany any resection of this
      vessel. Autogenous saphenous vein remains the graft conduit of choice, but
      prosthetic materials may be used. Graft patency and healing require appropriate
      concomitant soft-tissue coverage of any overlying mucosal or cutaneous defects.

PMID- 8159432
TI  - Bridging the medicine communication gap: the nursing connection.

PMID- 8159433
TI  - Clinical practice guidelines Q and A.

PMID- 8159434
TI  - Effects of Kelatorphan and morphine before and after noxious stimulation on
      immediate-early gene expression in rat spinal cord neurons.
AB  - Expression of the immediate-early genes (IEG) c-FOS, NGF1-A and c-JUN was induced
      by noxious thermal stimulation in neurons of the rat spinal cord dorsal horn.
      Intravenous injection of Kelatorphan (5, 10 and 20 mg/kg), an inhibitor of
      multiple enkephalin-degrading enzymes, 20 min before noxious stimulation reduced
      the overall number of dorsal horn neurons expressing c-FOS and NGF1-A by up to 20
      30%. While c-FOS expression was suppressed in superficial and deep laminae of the
      spinal cord, NGF1-A and c-JUN was only suppressed in superficial laminae.
      Morphine (5, 7.5 and 10 mg/kg) produced a dose-dependent reduction of c-FOS
      expression by up to 70% only when injected before noxious stimulation. Morphine
      injected 10 min after the noxious treatment was virtually ineffective. The
      depressant effect of Kelatorphan and morphine could be prevented by prior
      application of the opioid antagonist naloxone. Naloxone itself slightly increased
      the overall number of c-FOS-positive neurons in all laminae of the spinal cord.
      The present data support the existence of a tonic release of endogenous opioid
      peptides at the spinal level and show that inhibition of their peptidase-induced
      degradation modulates IEG expression in dorsal horn neurons of the rat. The
      finding that opioid agonists were ineffective when applied after stimulation
      underline the necessity of pre-emptive analgesia to prevent long-term activity
      dependent changes in spinal cord neurons.

PMID- 8159435
TI  - The dilemma of conversion from systemic to epidural morphine: a proposed
      conversion tool for treatment of cancer pain.
AB  - There is lack of concensus over what constitutes an appropriate method to affect
      an equianalgesic conversion from systemic to epidural morphine. A systematic
      approach to calculate the appropriate starting dose for epidural morphine is
      needed. A model is proposed here and data from a pilot study are described
      supporting the concept as well as its utility in the clinical setting. Several
      key factors may have an impact upon the selection of a starting dose in the
      opioid-tolerant cancer population such as pain severity, age, previous systemic
      opioid use, and presence of neuropathic pain. A conversion tool was developed
      taking these 4 factors into account and was tested in a small number of patients
      with cancer pain. The rationale for this approach is explored. Four case examples
      are presented to demonstrate the utilization of the tool and the effectiveness of
      this formula for clinical practice. Further study is needed to firmly establish
      the validity and reliability of this tool.

PMID- 8159436
TI  - Comments on Maves et al., Pain, 54 (1993) 57-69.

PMID- 8159437
TI  - Selection of patients undergoing neurolytic superior hypogastric plexus block.

PMID- 8159438
TI  - Morphine insensitive allodynia is produced by intrathecal strychnine in the
      lightly anesthetized rat.
AB  - The acute blockade of spinal glycinergic inhibition with intrathecal strychnine
      (i.t. STR; a glycine antagonist) in rats induces a change in somatosensory
      processing which is very similar to the sensory dysesthesia of clinical neural
      injury pain. In the present study, the effects of i.t. STR were examined in
      urethane-anesthetized rats. Noxious paw pinch (PP) or tail immersion (TI) in 55
      degree C water evoked a pronounced pressor response, increased heart rate (HR)
      and desynchronized the electroencephalogram; a non-noxious, hair deflection (HD)
      elicited only minor cardiovascular responses. After i.t. STR (40 micrograms), an
      identical HD stimulus evoked markedly enhanced cardiovascular responses,
      resembling those evoked by noxious stimuli, and a HD-evoked motor withdrawal was
      observed. Consistent STR-dependent responses were only observed if a light plane
      of anesthesia was maintained for the duration of the experiment. The effects of
      i.t. STR were dose-dependent and reversible, lasting 15-30 min. Spinal morphine
      (50 micrograms) completely abolished the cardiovascular responses to PP and TI,
      but the HD-evoked, STR-dependent cardiovascular and motor withdrawal responses
      remained unchanged. In contrast, the non-selective excitatory amino acid
      antagonist, gamma-D-glutamylglycine (DGG; 50 micrograms) was effective in
      suppressing both the STR-dependent cardiovascular and motor withdrawal responses.
      These data suggest that STR-dependent responses evoked by non-noxious stimuli are
      mediated by mechanisms distinct from those of conventional noxious stimuli and
      that i.t. STR may be useful for investigating the spinal pharmacology of
      somatosensory processing following the loss of spinal glycinergic inhibition.

PMID- 8159439
TI  - Sympathetic activation of cat spinal neurons responsive to noxious stimulation of
      deep tissues in the low back.
AB  - Prior findings from diverse studies have indicated that activity in axons located
      in the lumbar sympathetic chains contributes to the activation of spinal pain
      pathways and to low back pain; these studies have utilized sympathetic blocks in
      patients, electrical stimulation of the chain in conscious humans, and
      neuroanatomical mapping of afferent fiber projections. In the present study,
      dorsal horn neurons receiving nociceptor input from lumbar paraspinal tissues
      were tested for activation by electrical stimulation of the lumbar sympathetic
      chain in anesthetized cats. Of 83 neurons tested, 70% were responsive to
      sympathetic trunk stimulation. Excitatory responses, observed in both nociceptive
      specific and wide-dynamic-range neurons, were differentiable into two classes:
      non-entrained and entrained responses. Non-entrained responses were attenuated or
      blocked by systemic administration of the alpha-adrenergic antagonist
      phentolamine and are thought to result from sympathetic efferent activation of
      primary afferents in the units' receptive fields. Entrained responses were
      unaffected by phentolamine and are thought to result from electrical activation
      of somatic and/or visceral afferent fibers ascending through the sympathetic
      trunk into the dorsal horn. These findings from nocireceptive neurons serving
      lumbar paraspinal tissues suggest that low back pain may be exacerbated by
      activity in both efferent and afferent fibers located in the lumbar sympathetic
      chain, the efferent actions being mediated indirectly through sympathetic-sensory
      interactions in somatic and/or visceral tissues.

PMID- 8159441
TI  - Response of chronic neuropathic pain syndromes to ketamine: a preliminary study.
AB  - Hyperactivity of N-methyl-D-aspartate (NMDA) receptors may be one of the factors
      in the genesis of neuropathic pain. Ketamine is an NMDA-blocking agent widely
      used in human medicine. Ketamine (at 250 mcg/kg i.v. slow push) was administered
      to 6 patients for control of chronic neuropathic pain syndromes in double-blind
      placebo-controlled fashion. All 3 patients with peripheral nervous system (PNS)
      disease-related pain, and 2 of 3 patients with central pain and dysesthesia
      syndromes responded with a temporary decrease in the rating of ongoing pain. The
      allodynia, hyperalgesia and after-sensation present in 5 patients improved after
      the administration of ketamine. Dose-response estimation in 2 patients with PNS
      related neuropathic pain revealed that ketamine was effective in dose-related
      fashion. Continuous subcutaneous infusion of ketamine administered to 1 patient
      with PNS-related neuropathic pain caused no additional improvement in pain
      control but caused intolerable cognitive and memory side effects. In contrast,
      side effects during single-dose injections were mild and well tolerated. Ketamine
      affected the evoked pain and associated after-sensation in chronic neuropathic
      pain syndromes more than the ongoing constant pain.

PMID- 8159440
TI  - Effect of short-term hyperglycemia per se on nociceptive and non-nociceptive
      thresholds.
AB  - Previous animal and human studies have indicated that nociceptive thresholds are
      decreased by acute hyperglycemia. The results of these studies may be challenged
      due to methodological problems. We therefore conducted a double-blind,
      controlled, cross-over study on the effect of acute hyperglycemia on nociceptive
      and non-nociceptive thresholds in 10 type 1 (insulin-dependent) diabetic patients
      (diabetes < 5 years) without symptoms or clinical signs of peripheral neuropathy.
      During an overnight fast, blood glucose concentration was normalized by refract
      insulin injections. Then, blood glucose was kept at 6 mmol/l for 3 h by an
      intravenous infusion of glucose and insulin. On one study day, blood glucose was
      kept at 6 mmol/l for a further 3 h and on another day, blood glucose was elevated
      to 12 mmol/l during 0.5 h by additional glucose infusion and kept at that level
      for 2.5 h. Sensory testing was carried out twice during the initial 3 h with
      euglycemia and 3 times during the following period with either hyper- or
      euglycemia. The test procedure included determination of pain detection and pain
      tolerance thresholds to heat (wrists) and pressure (fingers) as well as detection
      thresholds to warmth/cooling (wrist), vibration (finger), and mechanical (wrist)
      stimulation. The changes in neither nociceptive nor non-nociceptive thresholds
      showed any statistically significant differences between the 2 study days. The
      pressure pain detection and tolerance thresholds showed, however, minor decreases
      at each of the test days, probably due to cutaneous sensitization caused by the
      repeated measurements. Compared to baseline, the pressure pain thresholds
      decreased significantly on the day with hyperglycemia. None of the other
      thresholds showed such changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159442
TI  - The NMDA antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) has
      antinociceptive effect after intrathecal injection in the rat.
AB  - This behavioral study was performed in order to delineate the antinociceptive
      effects of and the influence on motor function of a highly potent, competitive
      NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
      (CPP). After intrathecal (i.t.) administration of CPP to chronically catheterized
      rats, antinociception was studied in 3 different nociceptive tests: the tail
      flick test, the hot-plate test, and the formalin test. The lowest dose producing
      visible motor dysfunction was 1 nmol, with 2 of 8 animals showing slight ataxia.
      Dose-related motor dysfunction and apparent sedation was present after 5 and 10
      nmol. Dose-related antinociception was evident in the thermal tests following
      doses that produced little or no motor dysfunction. In the tail-flick test, the
      antinociceptive effect was attenuated at higher doses, resulting in a bell-shaped
      dose-response relationship. Dose-related antinociception was found in both the
      first and second phase of the formalin test following doses from 0.25 up to 1
      nmol. The present study shows that the competitive NMDA antagonist CPP has an
      antinociceptive effect in doses that do not affect motor function. Furthermore,
      antinociception was evident in both phasic and tonic nociceptive tests. Finally,
      the dose-response relationship in the tail-flick test was bell-shaped. As
      discussed this indicates that NMDA receptors may be involved in functionally
      divergent nociceptive systems.

PMID- 8159443
TI  - Effects of extracorporeal shock-wave lithotripsy on referred hyperalgesia from
      renal/ureteral calculosis.
AB  - In patients suffering from colics due to calculosis of one upper urinary tract
      the evolution in time of referred parietal hyperalgesia after stone fragment
      elimination promoted by extracorporeal shock wave lithotripsy (ESWL) was studied.
      Before ESWL, all patients presented clinical evidence (positivity to
      dermographism and Head's procedure, pinch palpation, digital pressure and
      Giordano's manoeuver) and instrumental signs (significant lowering of pain
      threshold to electrical tissue stimulation) of cutaneous, subcutaneous and
      muscular tissue hyperalgesia in the lumbar region of the affected side. After
      ESWL, hyperalgesia decreased in the three tissues, as shown by progressive change
      in the clinical tests and an increase in pain threshold to electrical stimulation
      in relation to the extent of stone fragment expulsion. In the stone-free
      condition, hyperalgesia had disappeared in the skin but remained to a mild and
      moderate extent in the subcutaneous tissue and muscle respectively. It is
      concluded that the persistence in time of referred hyperalgesia is only in part
      linked to the continuing presence and activity of the stone in the urinary tract.
      To a certain extent, the phenomenon seems to become independent of the primary
      focus, possibly as a result of plastic neuronal changes in the central nervous
      system which, triggered by afferent visceral inputs, are maintained even after
      their removal.

PMID- 8159444
TI  - The efficacy of oral splints in the treatment of myofascial pain of the jaw
      muscles: a controlled clinical trial.
AB  - Oral splints are widely used in the treatment of myofascial pain of masticatory
      muscles, even though their mechanism of action is unknown. The present study
      evaluated the therapeutic efficacy of splints using a parallel, randomized,
      controlled and blind design. Following a sample size estimation, 63 subjects were
      recruited and assigned to 3 groups: (1) passive control: full occlusal splint
      worn only 30 min at each appointment; (2) active control: palatal splint worn 24
      h/day; and (3) treatment: full occlusal splint worn 24 h/day. On each of 7 visits
      over 10 weeks, subjects rated on 100 mm visual analogue scales their pain
      intensity and unpleasantness at rest and after experimental mastication. The
      effect of pain on the quality of life was also rated on category scales. All pain
      ratings decreased significantly with time, and quality of life improved for all 3
      groups. However, there were no significant differences between groups in any of
      the variables. These data suggest that the gradual reduction in the intensity and
      unpleasantness of myofascial pain, as well as the improvement of quality of life
      during the trial, was non-specific and not related to the type of treatment.

PMID- 8159445
TI  - Characterization of a neuropathic pain model: sciatic cryoneurolysis in the rat.
AB  - Cryoanalgesia, the technique of freezing peripheral nerves, is used clinically
      for the treatment of postoperative and chronic pain. Paradoxically, this same
      technique produces characteristics in a rat model suggestive of neuropathic pain.
      We have developed a peripheral neuropathy model by freezing the proximal sciatic
      nerve (sciatic cryoneurolysis, SCN) using a cryoprobe cooled to -60 degrees C in
      a 30/5/30 sec freeze-thaw-freeze sequence. Each freeze cycle produced a transient
      ice ball on the surface of the nerve. These studies provide behavioral evidence
      that SCN is a valid mononeuropathy animal model. All animals demonstrate some
      degree of autotomy following SCN. The average onset of autotomy occurs 4 days
      postoperatively and peaks in severity and incidence at 14 days. By examining the
      latency of responses to a noxious heat stimulus, we have shown there is no direct
      relationship between an hypoesthetic paw and autotomy, i.e., autotomy did not
      occur immediately after the freeze lesion when the limb was dysfunctional.
      Rather, autotomy peaked when sensation was returning to the affected limb. The
      transient time course of certain behaviors including hypoesthesia and possible
      return of limb sensation, autotomy, touch-evoked allodynia, foot edema and the
      presence of spontaneous nociceptive behaviors demonstrate a multiple phase
      nociceptive process. The temporary nature of these nociceptive behaviors is in
      sharp contrast to the prolonged bilateral mechanical allodynia evident when these
      behaviors subside. The surgical anesthetics used during the SCN procedure are
      shown to variably alter or suppress autotomy following SCN.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8159447
TI  - The "catch-22" for teaching hospitals.

PMID- 8159446
TI  - The cutaneous withdrawal reflex in human neonates: sensitization, receptive
      fields, and the effects of contralateral stimulation.
AB  - The threshold of a cutaneous withdrawal reflex, elicited by calibrated von Frey
      hairs applied to the foot and leg, has been used to study the development of
      spinal sensory processing in a group of 50 preterm and full-term infants ranging
      from 27.5 to 42.5 weeks postconceptional age (PCA). Data sets (108) were
      collected on initial threshold, the effects of repeated innocuous stimuli, the
      receptive field of the withdrawal reflex, and the effect of a contralateral
      stimulus. As reported previously (Fitzgerald et al. 1988, 1989), there was a
      correlation between PCA and initial threshold. The mean threshold at 29 weeks was
      0.237 g (S.E.M. 0.042), whereas the mean threshold at 41 weeks was 0.980 g
      (S.E.M. 0.134). Repeated stimulation with von Frey hairs led to a significant
      lowering of threshold or "sensitization" of the reflex in infants of up to 35
      weeks PCA. Thereafter, the decrease in threshold was not significant, and
      habituation was observed. From 27.5 weeks PCA, it was possible to elicit the
      withdrawal reflex from the whole limb as far up as the top of the thigh and
      buttock. Below 30 weeks PCA, the thresholds within this receptive field were
      uniform, but after 30 weeks a gradient of thresholds was observed increasing
      progressively from the sole of the foot towards the knee. The application of a
      maintained stimulus to the contralateral limb significantly inhibited withdrawal
      reflex responses to ipsilateral von Frey hair stimulation, across all age bands.
      These results illustrate postnatal changes in sensory processing within the human
      spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159448
TI  - Medical therapy of low back pain.

PMID- 8159449
TI  - Outcome studies of hip fractures. A functional viewpoint.
AB  - As the success rate for repair of hip fractures continues to increase, emphasis
      is shifting to outcomes beyond the simple fracture repair to include restoration
      of function. The orthopaedist's role is critical in understanding, assessing, and
      determining patient prognosis with respect to functional outcome. Multiple
      factors are predictive of outcome following hip fracture; these factors may
      facilitate the orthopaedist's decision making in providing care that will
      maximize restoration relative to a patient's premorbid ability to walk and live
      independently. This review of past research summarizes our current knowledge of
      hip-fracture outcomes and prognostic indicators.

PMID- 8159450
TI  - Rhabdomyolysis. A primer for the orthopaedist.
AB  - Orthopaedic surgeons may be confronted with a variety of medical problems that
      demand recognition and treatment. These may range in severity from a mild case of
      rheumatoid arthritis to a life-threatening pulmonary embolism. Rhabdomyolysis is
      a serious problem that must be recognized early to avoid grave renal
      consequences. This disorder is characterized by significant muscle injury giving
      rise to nephrotoxic breakdown products in the bloodstream. As many as 33% of
      these patients will suffer acute renal failure. Many orthopaedic patients may be
      at high risk for rhabdomyolysis, and the orthopaedic surgeon should be familiar
      with its diagnosis and treatment.

PMID- 8159451
TI  - Measured femoral density by dual-energy X-ray absorptiometry as a function of
      rotation.
AB  - The use of projectional techniques to evaluate bone density of the proximal femur
      has the potential to be adversely affected by rotation along the head/condyle
      axis, due to the complex geometry of the region being examined. To experimentally
      investigate the magnitude of variation attributable to rotation, the bone density
      of a cadaveric femur, placed in a water bath to simulate soft tissue, was
      measured as a function of rotation by using a dual-energy x-ray absorptiometry
      (DXA) system. It was found that 10 to 15 degrees of rotation was the minimum
      deviation from the baseline of the femoral head perpendicular to the x-ray beam
      required to produce statistically significant (P = .95) changes in measured bone
      density. The magnitude of the variation at these rotations ranged from 2.5% for
      the trochanter to 5.0% for the femoral neck. Even though variation along the axis
      described is difficult to precisely control in the clinical setting, the
      magnitude of density errors attributable to these variations should not adversely
      affect the utility of projectional density measurement techniques.

PMID- 8159452
TI  - Shoulder proprioception. Effect of joint laxity, joint position, and direction of
      motion.
AB  - Recently, considerable importance has been ascribed to that portion of shoulder
      stability which may be provided by active muscle forces. Joint proprioception
      likely has a considerable role in muscular stabilization of the shoulder by
      providing information to the central nervous system for the management of
      muscular activity. Normal human shoulder proprioception has not yet been
      thoroughly characterized. We have measured shoulder joint proprioception in a
      population of subjects without known shoulder abnormalities by quantifying the
      subjects' ability to correctly detect passive shoulder rotation in the abducted
      shoulder. We have found absolute angular proprioception to range from an average
      "best" of 0.78 degrees to a "worst" of 1.08 degrees. Individuals who have
      clinically determined generalized joint laxity are significantly less sensitive
      in proprioception (P < .002). Detection of external rotation is significantly
      more sensitive than detection of internal rotation (P < .001). Detection of
      external rotation becomes significantly more sensitive as the limit of external
      rotation is approached. We have concluded that these findings suggest capsular
      tightening as one possible mechanism for shoulder proprioception.

PMID- 8159453
TI  - Hypocalcemic-induced tetany that causes triceps and bilateral quadriceps tendon
      ruptures.
AB  - Traumatic ruptures of the triceps are very rare among tendon injuries. A unique
      case of hypocalcemic tetany that induced spontaneous triceps tendon avulsion with
      associated bilateral quadriceps tendon ruptures is reported. The current
      orthopaedic literature is reviewed, and a new application of an existing surgical
      treatment for repair of the major tendon ruptures is described.

PMID- 8159454
TI  - Compression of the ulnar nerve at the elbow in association with synovial cysts.
AB  - Compression neuropathies around joints in association with synovial cyst
      formation are rare events. A case of a posttraumatic ulnar nerve palsy in a
      patient with osteoarthritis of the elbow is presented. At operative exploration
      of the cubital tunnel, the ulnar nerve was found to be compressed by a synovial
      cyst. Cyst formation should be considered in determining the etiology of
      compression neuropathies in patients with posttraumatic and degenerative
      processes occurring around the joints.

PMID- 8159455
TI  - A method of pediatric short arm cast application.
AB  - A method for comfortable and efficient application of pediatric short arm casts
      is described.

PMID- 8159456
TI  - A newborn with bilateral hip flexion contractures and clubfeet.
AB  - The following case is presented to illustrate the roentgenographic and clinical
      findings of a condition of interest to the orthopaedic 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- 8159457
TI  - Use of the orthofix limb alignment grid in the treatment of infantile tibia vara.
AB  - The use of a dome osteotomy in the treatment of infantile tibia vara is
      reportedly associated with insufficient intraoperative assessment of the
      correction achieved. This article discusses a method to overcome this problem and
      the long-term advantages of using a dome osteotomy in the treatment of this
      disease.

PMID- 8159458
TI  - Subcellular localization of Pfs16, a Plasmodium falciparum gametocyte antigen.
AB  - We have used immunoelectron microscopy to investigate the subcellular location of
      Pfs16 in Plasmodium falciparum. It was detected in the outer membrane region of
      gametocytes and more specifically on the parasitophorous vacuole membrane (pvm),
      since, during gametogenesis when the pvm disintegrates, the majority of the
      antigen was detected on the remains of this membrane in multilaminated whorls and
      not on the gamete plasma membrane. The antigen was also present on other
      gametocyte cellular structures, including those which we believe to be Garnham
      bodies, present in the host cell cytoplasm of some gametocytes. The antigen was
      present too on the membrane surrounding cytosomes and the resulting food vacuoles
      in the parasite cytoplasm.

PMID- 8159459
TI  - Phylogeny and evolution of the piroplasms.
AB  - Small subunit ribosomal RNA (srRNA) genes of three Theileria species, one
      Cytauxzoon and four Babesia species were amplified using the polymerase chain
      reaction (PCR), cloned and sequenced. Our sequences were aligned with srRNA
      sequences previously published for eight species of Apicomplexa, one ciliate and
      one dinoflagellate, the last two being included as free-living outgroup species.
      Phylogenetic relationships between the organisms were inferred by four
      independent methods of phylogenetic tree construction using the ciliate Oxytricha
      nova to root the trees. Our trees fail to show a consensus branching order. They
      do, however, clearly indicate that the theilerias form a monophyletic taxon
      derived from a paraphyletic group which includes the species B. equi, C. felis
      and B. rodhaini. The distance trees indicate that the babesias sensu stricto (B.
      canis, B. caballi, B. bigemina and B. bovis) form another monophyletic taxon
      which diverged before the theilerias separated from the above-mentioned
      paraphyletic group. The parsimony and maximum likelihood trees suggest that the
      babesias and theilerias are sister taxa, both of which were derived from the
      paraphyletic group.

PMID- 8159460
TI  - The amount of acetylcholinesterase on the parasite surface reflects the
      differential sensitivity of schistosome species to metrifonate.
AB  - Acetylcholinesterase (AChE) is present in all stages of the life-cycle of
      schistosomes and is located in muscle and on the surface of the parasite.
      Metrifonate is a drug that inhibits AChE. We compared the AChEs from three
      schistosome species (Schistosoma mansoni, Schistosoma haematobium and Schistosoma
      bovis) that have different susceptibilities to metrifonate in vivo. Sensitivities
      to AChE inhibitors were similar. The subunits of AChE were 110 kDa and 76 kDa and
      the dominant molecular form of AChE was a G2 form in all three species. This was
      the major form on the tegument while additional molecular forms were associated
      with the internal tissues. Differences in relative amounts of AChE activity
      between these species were found in the adults but not in the schistosomula. At
      the adult stage the major difference between species lay in the relative amounts
      of AChE activity in their teguments. S. haematobium teguments carried 20 times
      and S. bovis 6.9 times the activity present on S. mansoni teguments. These
      quantitative differences associate with the relative sensitivities of these
      species to metrifonate.

PMID- 8159461
TI  - Trypanosoma brucei: characterization of protein kinases that are capable of
      autophosphorylation in vitro.
AB  - Autophosphorylation by protein kinases has been implicated as an important
      control mechanism in signal transduction and growth regulatory pathways in
      mammalian cells. We have set out to investigate whether any such
      autophosphorylating protein kinase activities can be found in Trypanosoma brucei.
      In order to do this, we have developed a system for characterizing such protein
      kinase activities using an in vitro assay. This assay was carried out by
      fractionation of trypanosome lysates using isoelectric focusing gel
      electrophoresis followed by incubation of the gel in gamma 32P-labelled
      nucleotide triphosphate and subsequent autoradiography. We have identified two
      classes of autophosphorylating protein kinase activities. In the first class all
      were dependent on ATP as the phosphate donor substrate and were all found to have
      a molecular size of 60 kDa. Differences in the activity of these protein kinases
      were observed between the bloodstream and procyclic life-cycle stages.
      Furthermore, the addition of mammalian epidermal growth factor to bloodstream
      stage lysates stimulated an additional activity. The second class of
      autophosphorylating protein kinases utilized GTP as the phosphate donor and were
      all found to be 90 kDa in size. Stage-specific differences were also observed in
      the activity of these protein kinases.

PMID- 8159462
TI  - The population age structure and reproductive biology of Gyrodactylus salaris
      Malmberg (Monogenea).
AB  - Gyrodactylus salaris has recently become a major pathogen of Atlantic Salmon
      (Salmo salar) in Norway. The survivorship, population age structure and pattern
      of insemination of G. salaris were studied to determine the extent to which this
      species reproduces sexually. The age-specific mortality schedule of G. salaris
      could be described by an exponential model but day to day variations were large,
      with an increase in mortality after each birth. Modelling population growth using
      the best fit mortality schedule indicated that, at stable age structure, 35% of
      the population would consist of newborn and pre-1st birth flukes. Using testis,
      penis and embryo development, pre-1st birth and immediately post-1st birth flukes
      could be unambiguously identified, and established infections were found to
      contain 35% pre-1st birth flukes, as predicted. The proportion of pre-1st birth
      flukes in newly established infections was significantly smaller, probably
      because of differences in the rate of transmission between newborn and older
      flukes. Gyrodactylus salaris is relatively long-lived, and more than 40% of the
      population may survive to give birth for the third time. As gyrodactylids are
      protogynous, and the first daughter is probably produced asexually, this long
      lived strategy ensures that a large part of the G. salaris population possesses a
      functional male system, and that the asexually derived flukes are a smaller
      component of the total population in this species. Flukes with whorls of
      inseminated spermatozoa within the seminal receptacle were found in all age
      groups possessing a functional male system, and were interpreted as having been
      cross-inseminated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159463
TI  - The relationship between Pseudodiplorchis americanus (Monogenea) density and host
      resources under controlled environmental conditions.
AB  - A previous study has shown that, under natural conditions, energy reserves of the
      desert toad, Scaphiopus couchii, are negatively related to the density of
      infection by Pseudodiplorchis americanus. However, this was based predominantly
      on collections of active animals from breeding congregations and inevitably
      selected toads which were in good condition. The parasite, a blood-feeding
      monogenean, occurs in burdens of up to 30 worms/host (mean intensity 6
      worms/host) and represents a significant drain on reserves because the host does
      not feed during a 10-month hibernation. Field studies cannot resolve the
      possibility that larger worm densities are not observed in nature due to parasite
      induced host mortality. The present study was conducted during investigations of
      P. americanus development and survival under controlled laboratory conditions,
      utilizing experimentally infected hosts which created worm densities larger than
      those observed in natural populations. At all temperature regimes, infected
      animals had smaller fat bodies than those uninfected but differences were
      generally not statistically significant due to large individual variations,
      presumably resulting from variations in past feeding efficiency. At cool
      temperatures (15-20 degrees C) there was no density-dependent effect on host fat
      body weight, and at a diurnal temperature cycle of 20-34 degrees C (simulating
      that experienced by host and parasite during the summer months), the effects of
      high temperatures were greater than the effects of infection, due to increased
      toad metabolic rates. The most significant effects of P. americanus were observed
      in hosts that began hibernation in relatively poor condition and experienced
      moderate temperatures (25 degrees C) during hibernation. The toads generally
      maintained packed blood cell levels (PCV) levels even when fat body weights were
      low, but infected animals had a lower PCV irrespective of fab body levels. In
      animals unfed after field collection, PCV was reduced in uninfected toads and was
      even lower in infected animals. Although very heavily infected toads (burdens of
      35-95 worms/host) were generally in poorer condition than uninfected toads they
      still survived long-term hibernation under extreme nutritional stress. This study
      therefore confirmed observations made in field studies that there is a density
      dependent relationship between the hosts' survival prospects and P. americanus
      infection. However, given the large variability in feeding efficiency and stored
      resources between individual toads, there is no evidence that the most heavily
      infected toads would have been unrepresented in field samples due to parasite
      induced mortality.

PMID- 8159464
TI  - Survival of Pseudodiplorchis americanus (Monogenea) under controlled
      environmental conditions.
AB  - Populations of Pseudodiplorchis americanus infecting the desert toad, Scaphiopus
      couchii, have previously been shown to be remarkably stable from year to year,
      despite wide variation in conditions promoting invasion. The present study aimed
      to document the survival of both first-year and pre-existing adults under
      controlled laboratory temperatures. First-year worm survival in experimentally
      infected toads was shown to be very high for the first 5 months after migration
      to the definitive site, and there was no difference in survival at 25 degrees C
      or 15-20 degrees C. There was also no density-dependent survival during the same
      period: 20% of worms were recovered from the host urinary bladder, irrespective
      of initial intensities. After the first 5 months, there was a progressive loss of
      worms in toads maintained at 25 degrees C but not at 15-20 degrees C. Pre
      existing adult populations were shown to be virtually identical to those under
      natural conditions for the first 4 months after toad capture. Following this, at
      25 degrees C, populations declined and no pre-existing adults were recovered
      after 11-14 months. There was no such loss of pre-existing adults at 15-20
      degrees C for up to 14 months. A diurnal temperature cycle of 20-34 degrees C
      (simulating temperatures during the desert summer) did not lead to a significant
      loss of worms. These observations suggest that during one annual cycle in the
      desert, when temperatures remain above 20 degrees C for less than 6 months, most
      adult worms established in the host urinary bladder will survive to the next
      transmission opportunity. However, the similar longevity of first-year and pre
      existing adults in laboratory maintained toads shows that loss of worms cannot be
      due solely to parasite ageing. Temperature-dependent survival of P. americanus is
      suggestive of a host immune response. Low temperatures, which inhibit parasite
      growth and development, are essential for the survival of P. americanus.

PMID- 8159465
TI  - Changes in host muscles induced by excretory/secretory products of larval
      Trichinella spiralis and Trichinella pseudospiralis.
AB  - Excretory/secretory (ES) products obtained by in vitro culture of infective-stage
      larvae of Trichinella spiralis and T. pseudospiralis were injected
      intramuscularly at various intervals into mice. Mini-osmotic pumps containing T.
      spiralis ES products were also implanted subcutaneously and intraperitoneally
      into rats. The introduction of ES materials into muscles elicited extensive
      lesions which included dissolution of myofibres, mobilization of mononuclear and
      polymorphonuclear leucocytes, angiogenesis, hypertrophy of myonuclei, myotube
      formation, mitosis, muscle bundles becoming rounded and separated from each
      other, disappearance of Z, I and A bands of sarcomeres, increase in endoplasmic
      reticulum and Golgi complexes, decrease in glycogen and relocation of
      mitochondria. These are considered as degenerative/regenerative changes of
      muscles to injury. Immunodominant epitopes of specific 45-53 kDa glycoproteins in
      ES antigens of T. spiralis could not be detected in hypertrophic nuclei of
      injected muscles by using polyclonal and monoclonal antibodies and
      immunocytochemical methods. ES products of T. spiralis failed to stimulate
      unsensitized lymphocytes in the lymphocyte transformation test. Infective-stage
      larvae of T. spiralis released from muscles were found capable of forming nurse
      cells after injection subcutaneously into rats. It is postulated that the
      invasion of muscles by trichinellids elicits two independent events, i.e. a
      general degenerative/regenerative response of muscles and a specific change in
      genomic expression of myonuclei. The two events are probably mediated by
      different effector molecules.

PMID- 8159466
TI  - The rapid development of the glucose transport system in the excysted metacestode
      of Hymenolepis diminuta.
AB  - Temporal changes in glucose transport capacity in excysted scoleces of
      Hymenolepis diminuta were examined. Assays involved incubation for 1 min in
      [3H]glucose after pre-incubation for 1 min to 8 h in saline. There were two
      abrupt increases in uptake velocity, a relatively small one between 15 and 75
      min, and a large one between 5 and 6 h, during which the Vmax increased from 0.36
      to 2.49 nmol/25 larvae/h. The second increase was unaffected when the pre
      incubation saline contained 5 mM glucose, but it was completely blocked when the
      excysted larvae were pre-incubated in Ca(2+)-free saline. Abrupt glucose
      transport changes did not occur in intact cysticercoids or in scoleces when the
      substrate was [3H]leucine or [3H]uracil. Arrhenius plots (log V versus
      1/temperature, 10-42 degrees C) were linear for intact cysticercoids, but were
      biphasic for both scoleces and adults with discontinuities at 20 +/- 1 degrees C.
      Thus, 'activation' of the excysted scolex seemed to involve a specific, Ca(2+)
      dependent increase in number of glucose transporters functioning in the worm
      surface. The Arrhenius plots indicated that development in the final host does
      not involve a major change in lipid composition of the parasite's membranes.

PMID- 8159467
TI  - Cyclosporin A: drug treatment in vivo affects the kinetics of [14C]glucose
      transport in Hymenolepis microstoma in vitro.
AB  - The transport of [14C]glucose by Hymenolepis microstoma in vitro following in
      vivo treatment with cyclosporin A (CsA) was determined over a range of
      concentrations. For untreated (control) worms glucose uptake showed saturation
      kinetics with a small diffusion component. Estimates of the maximum velocity of
      glucose uptake (Vmax) and the affinity of substrate for the glucose transporter
      (Kt) revealed that untreated 8-day-old worms had a Vmax twice that of 15-day-old
      worms and that younger worms had a lower Kt. An inverse relationship was
      demonstrated between log10 worm weight and the rate of uptake of [14C]glucose,
      reflecting the relatively greater number of glucose transporters due to the
      larger surface area:volume ratio of smaller worms. Treatment of H. microstoma
      with CsA in vivo significantly increased the diffusion component of glucose
      uptake in vitro. Parasites from drug-treated mice had a significantly lower Vmax
      for glucose uptake than size-matched controls. The affinity of glucose for its
      transporter in CsA-treated worms (Kt) was not significantly different from size
      matched controls. Both juvenile and adult worms underwent transient depletion in
      total glycogen content after CsA treatment in vivo. The data confirm that CsA
      treatment in vivo disrupts the functional integrity of the worm tegument, one
      facet of which is impaired acquisition of glucose.

PMID- 8159468
TI  - A nematode FMRFamide-like peptide, SDPNFLRFamide (PF1), relaxes the dorsal muscle
      strip preparation of Ascaris suum.
AB  - PF1 (SDPNFLRFamide) is a FMRFamide-like peptide extracted from the free-living
      nematode Panagrellus redivivus. Here we show that this peptide causes a
      hyperpolarization of somatic muscle cells of the parasitic nematode Ascaris suum
      and a relaxation of the somatic muscle strip preparation. We have assessed
      whether or not the relaxation of Ascaris dorsal muscle strip by PF1 is due to (i)
      inhibition of the release of the excitatory neuromuscular junction transmitter
      acetylcholine (ACh), (ii) potentiation of the release of the inhibitory
      neuromuscular junction transmitter gamma-aminobutyric acid (GABA) or (iii) a
      direct inhibitory action of the peptide on the muscle cells. Under the
      experimental conditions described here, tonic ACh release does not seem to be
      involved in determining the resting membrane potential or resting tone of the
      Ascaris dorsal muscle strip and thus inhibition of tonic ACh release is unlikely
      to explain the relaxation elicited by the peptide. Furthermore, PF1 (100 nM-1
      microM) inhibited the contraction of the muscle strip elicited by bath
      application of ACh, suggesting either a direct inhibitory action of the peptide
      on the muscle cells or a potentiation of GABA release. In electrophysiological
      experiments, the reversal potential for the PF1 hyperpolarization was not the
      same as that for GABA. Thus, PF1 hyperpolarizes Ascaris muscle by a mechanism
      that does not involve stimulation of GABA release from inhibitory pre-synaptic
      terminals.

PMID- 8159469
TI  - [Molecular and cellular mechanisms of invasion of the intestinal barrier by
      Shigella flexneri].

PMID- 8159470
TI  - [Photoreceptor cells, circadian oscillators and control of the rhythmic
      production of melatonin. Perspectives].

PMID- 8159471
TI  - [Evaluation of rapid screening tests in the diagnosis of urinary infections].
AB  - Bacterial urine examination is the main bacterial examination used in
      microbiology laboratories. The comparative interest of urine aspect associated
      with rapid screening tests (catalase, leucocyte esterase, nitrite) and different
      urine examination methods (Gram stain of sediment, direct examination on Malassez
      cell and on centrifuged urine pellet) are evaluated for negative predictive value
      of urinary tract infection. In out-patient, the association urine aspect
      leucocyte esterase has the best negative predictive value for urinary tract
      infection (99.4%). Either in outpatients or in hospitalized patients, the
      association Gram stain of sediment-leukocyturia evaluation has the best negative
      predictive value for urinary tract infection (100%). This data allows in our
      population to give back negative results without culture.

PMID- 8159472
TI  - [Estimation with bacteriology of the evolution of nosocomial infections between
      1989 and 1991 in an university hospital].
AB  - The bacteriological laboratory data base was studied with an original software
      (Bacterio) and an appropriate method ("doubles" and early samples are not taken
      in account) to estimate the nosocomial infections. The incidence rates for 100
      hospitalizations at the University hospital of Nancy are 9.2, 8.2 et 8.2 for
      respectively 1989, 90 et 91. These values are corrected while taking into account
      a method's sensibility of 65%. The 1000 days of hospitalization's rates allow a
      better comparison between the medical departments. For the whole hospital, the
      results are respectively of 7.9, 7.2 and 7.5%. Even if the many bias described
      cannot always been checked, the method gives some evolutivity indicators which
      are very useful for the hygienists.

PMID- 8159473
TI  - Use of red blood cell indices (MCV, MCH, RDW) in monitoring chronic hemodialysis
      patients treated with recombinant erythropoietin.
AB  - Human recombinant erythropoietin (rHu-Epo) is now extensively used in chronic
      renal failures; this treatment, resulting in a correction of the severe anemias
      seen in hemodialysed patients, may in turn lead to a resistance to rHu-Epo
      therapy by reason of the shortage of erythropoiesis factors, such as iron,
      vitamin B12 and folates. The utility of the red cell indices (MCV, MCH, RDW) for
      detection of early iron, folate and B12 deficiencies was studied in eighteen
      hemodialysed patients with end-stage renal failure treated with rHu-Epo;
      Microcytosis (MCV < 80 fl) was found ineffective in detecting iron deficiencies
      as well as macrocytosis (MCV > 100 fl) in folate and B12 deficiencies, partly due
      to the high incidence of associated iron and folate deficiencies. Lowered MCH (<
      27 pg) was not more efficient than microcytosis in detecting early iron
      deficiencies. Increased RDW was the most sensitive feature for folate, iron and
      B12 deficiencies with respective sensitivities of 62.5%, 72% and 75%. The global
      specificity for detecting all deficiencies was 74%. However, high RDW values were
      not indicative of any type of deficiency; it may thus be concluded that RDW is a
      non expensive, non invasive and sensitive test, which allows a selection of
      hemodialysed patients treated with rHu-Epo for a complete investigation program,
      in order to detect early iron, B12 and folate deficiencies.

PMID- 8159474
TI  - [Calcitonin gene-related peptide (CGRP): a vasodilator neuropeptide with many
      potential applications].
AB  - CGRP (calcitonin gene-related peptide) is a potent vasodilator neuropeptide which
      acts on peri-arteriolar neurones and is implicated in the pathogenesis of
      numerous cardiovascular diseases. The synthesis of CGRP antagonists should be
      useful for the treatment of Raynaud's disease as well as migraine. There exists
      an homology between the structures of CGRP and pancreatic amylin and therefore an
      eventual role of CGRP in type II diabetes pathophysiology is currently being
      studied.

PMID- 8159475
TI  - Genomic techniques for identification of Leptospira strains.
AB  - Within the Leptospiraceae family, the genus Leptospira is divided into the
      pathogenic L. interrogans sensu lato and the saprophytic L. biflexa sensu lato.
      Based on DNA-DNA hybridization, L. interrogans sensu lato has been shown to
      contain 7 different genomic species. Each genomic species contains numerous
      serovars. Pulsed-field genetic studies performed during this work demonstrated a
      great heterogeneity of serovars, within genomic species, based on restriction
      length polymorphism analysis. In contrast, an identified serovar, despite the
      time and region of isolation, has been shown to be highly stable in its genomic
      structure. The most likely reasons for this finding include the long generation
      time of these bacteria and the lack of acquisition of heterologous DNA. New
      identification techniques, based on gene amplification, have been used for
      Leptospira strains. These techniques represent the first available to facilitate
      the study of the epidemiology of Leptospira.

PMID- 8159476
TI  - [Assay of cross-linking molecules of collagen (pyridinolines) in the study of the
      degradation of bone tissue and articular cartilage].
AB  - Recent studies aimed at studying the degradation of the fibrillar collagens of
      bone and articular cartilage have lead to the discovery of naturally fluorescent
      crosslinking compounds derived from lysine and hydroxylysine. These small
      molecules characterized by an aromatic 3-hydroxypyridinium ring are present in
      significant amounts only in bone (pyridinoline and deoxy-pyridinoline) and
      cartilage (pyridinoline). Diseases characterized by an increased degradation of
      the fibrillar collagenous network are associated with an increased urinary
      excretion of both compounds: Pyridinoline and deoxypyridinoline are currently the
      most sensitive and specific markers of bone resorption. The purpose of this paper
      is to review current knowledge in the area of collagen crosslinking molecules
      with special emphasis on the pyridinium crosslinking amino acids and their
      potential clinical application as a marker of bone and cartilage degradation.

PMID- 8159477
TI  - [Radio-isotope assays of vitamin B 12: value of the Kappa test in a multicenter
      evaluation].
AB  - Owing to the lack of a reference technique and of an international cobalamin
      (vitamin B12) standard, and the large discrepancy between laboratory norms, the
      authors performed a multicentric study to compare five RIA kits usually used.
      First, classical tests were used to evaluate the analytical performances of each
      kit. Results did not demonstrate any superiority of one kit over another.
      Secondly, B12 values were classified among three categories (low, normal and
      high) characterized by laboratory and then manufacturer norms. The concordance
      between these two "judgments" was evaluated with the Kappa coefficient. In
      addition, the Kappa index proved that the norms supplied by the manufacturer were
      better than those of laboratories. But mean Kappa coefficient established for
      each norm gave us an unsatisfactory result. Third, clinical informations allowed
      to improve the classification of the patients. New limits were defined for each
      technique and should be tested further, routinely in each laboratory.

PMID- 8159478
TI  - Developmental issues in managing children with diabetes.
AB  - Children who are newly diagnosed with insulin dependent diabetes mellitus (IDDM)
      are expected to learn a substantial amount of new information within a few
      hospital days. It is important for nurses who design lesson plans for the child
      with IDDM to assess the child's developmental capabilities in relation to the
      necessary skills required of diabetes management and understand the family
      influence on the child's ability to perform self-care.

PMID- 8159479
TI  - Initial adaptation in children with newly diagnosed diabetes and healthy
      children.
AB  - A cohort of children with newly diagnosed diabetes (n = 68) from four diabetes
      treatment centers in northeastern states were compared with a cohort of healthy
      peers (n = 40) 6 weeks following the diagnosis of diabetes in the ill children.
      Instruments used included the Children's Depression Inventory (CDI), State-Trait
      Anxiety Inventory for Children (STAIC), Coping Inventory (COPE), Child &
      Adolescent Adjustment Profile (CAAP), and Self Perception Profile for Children
      (SPPC). Results indicated no demographic differences between the two groups and
      no differences in scores on CDI, STAIC-state anxiety, and all subscales of the
      CAAP and SPPC. However, the children with diabetes were reported to demonstrate
      less withdrawal (11.6 +/- 3.0 versus 12.4 +/- 2.3) than their healthy peers and
      were more likely to cope by ventilating feelings (19.7 +/- 2.0 versus 18.7 +/-
      2.2). Parents reported that children with IDDM were less healthy (p < .001).
      These data suggest a less severe initial psychologic response to diabetes than
      might be expected and that there are differences in coping patterns among
      children with IDDM and children without chronic illness.

PMID- 8159480
TI  - The infant with diabetes mellitus: a case study.
AB  - Certain aspects of Type I diabetes mellitus are unique to children diagnosed in
      infancy. These include (a) initial symptoms of Type I diabetes that are easily
      overlooked by parents and may lead to a delayed diagnosis; (b) rapid progression
      to a critical state; and (c) recovery, teaching, and return to daily life.
      Specific nursing care concerns include psychosocial issues for families,
      technical skills, diet management, and hypoglycemia.

PMID- 8159481
TI  - "Think TB:" new focus for family assessment.
AB  - The growing incidence of tuberculosis (TB) among childrearing families introduces
      new challenges to pediatric nurses. The following four clinical stories have been
      developed from the authors' experiences with Hispanic families from high
      prevalence regions in order to emphasize the characteristics and conditions that
      nurses need awareness of when caring for patients with possible TB. These stories
      highlight common themes in families from other high-risk groups as well that may
      surface in pediatric nurses' practice. Collaboration between pediatric and TB
      control nurses becomes essential for vigilant control of the spread of this
      reemerging old disease.

PMID- 8159482
TI  - Childhood hypercholesterolemia: implications for nurse practitioners.
AB  - Universal versus targeted screening for hypercholesterolemia in children is
      currently a debatable practice issue. Nurse practitioners must decide which
      screening methods to incorporate into practice. Recommendations on evaluation and
      management of hyperlipidemia in children can aid nurse practitioners facing this
      decision.

PMID- 8159483
TI  - Family-centered care: the time has come.
AB  - The concept of family-centered care was first introduced in 1987. Since that
      time, legislation has mandated its implementation, training materials have been
      developed, and it has come to be considered "best practice." It is time now for
      pediatric nurses to learn strategies for implementation of family-centered care.

PMID- 8159484
TI  - Pediatric management problems: constitutional delay.

PMID- 8159485
TI  - Warfarin drug interactions.

PMID- 8159486
TI  - Accuracy and reliability of temperature measurement in the emergency department
      by instrument and site in children.
AB  - PURPOSE: 1. To determine the accuracy, precision, specificity, sensitivity,
      positive prediction, and negative prediction of TempaDOT, FirstTEMP, and Genius
      as compared to the glass mercury thermometer; 2. To determine the influence of
      age, behavior, febrile status, tympanic membrane bulge, presence of ear wax, and
      site on temperature readings; and 3. To determine the ability of each instrument
      to detect a shift in temperature after Tylenol. METHOD: A quasi-experimental,
      multiple-correlational design was used to study 960 temperature measurements
      obtained on 89 febrile and 83 afebrile children in an emergency unit. FINDINGS:
      TempaDOT was found to be the most accurate and most precise instrument for
      children ages 5 years and under with and without fevers. FirstTEMP was found to
      be most sensitive for temperatures above 37.5 degrees C and best in detecting
      shifts after Tylenol was given. Age, behavior, febrile status or tympanic
      membrane bulge did not significantly affect accuracy. The most accurate sites in
      order of accuracy were: oral axillary, aural, rectal. The order of precision of
      sites was: oral, aural, rectal, and axillary. Behavior did not significantly
      affect the precision. CONCLUSION: TempaDOT was found to be the most clinically
      useful temperature measurement instrument. FirstTEMP may be used as a screening
      tool to determine if antipyretic medication is working to decrease fevers.
      TempaDOT is recommended for use in emergency units to validate the presence or
      absence of fevers in children especially when the FirstTEMP reading is near 37.0
      38.8 degrees C.

PMID- 8159487
TI  - Professional new year's resolutions.

PMID- 8159488
TI  - Improving the primary care pediatric nurses provide to children and their
      families.
AB  - Pediatric nurses need to promote healthy behaviors and prevent disease and
      disability in the children for whom they care. This new column will help
      pediatric nurses keep abreast of strategies to improve primary care rendered to
      children and their families regardless of setting.

PMID- 8159489
TI  - EPSDT and health care reform.

PMID- 8159490
TI  - Pediatric skin care issues for the home care nurse: Part 2.

PMID- 8159491
TI  - Coban contains latex.

PMID- 8159492
TI  - Firearm death and injury in children and adolescents is also a serious problem.

PMID- 8159493
TI  - Laser therapy as a treatment for retinopathy of prematurity.
AB  - Laser therapy is an effective treatment for severe retinopathy of prematurity
      (ROP). The pathophysiology and classification of ROP are reviewed. The treatment
      regimen and nursing care involved with the use of lasers are described, including
      patient education. Laser therapy and cryotherapy are compared in terms of pain,
      infection, tissue damage, procedure time, and patient outcomes.

PMID- 8159494
TI  - Ethics consultation: an update on accountability issues.
AB  - Nurses in a community hospital pediatric unit are struggling with the issue of
      how to care for a severely handicapped newborn. The parents are confused and
      cannot decide whether to approve a series of operations that will extend the
      infant's life or to request only palliative care. Where can the nursing staff go
      for help with these issues? Does the hospital have a bioethics service? What
      should nurses expect if they avail themselves of this service? Would members of
      the bioethics service decide what should be done? How would the family be
      involved?

PMID- 8159495
TI  - Popular culture and family models.

PMID- 8159496
TI  - Family-centered care: shifting orientation.
AB  - To practice in a family-centered manner requires nurses to shift from a
      professionally-centered view of health care to a collaborative model that
      recognizes families as central in a child's life and their values and priorities
      as central in the plan of care. Nursing strategies to promote the family's role
      as primary caregiver for their child include recognizing and accepting diverse
      styles of family coping, helping families recognize their strengths and methods
      of coping, reassuring parents regarding their essential role, and facilitating
      family involvement and caregiving. The use of communication models such as LEARN
      and the Nursing Mutual Participation Model of Care can facilitate collaborative
      parent-professional relationships. A brief review of research on families of
      children critically or chronically ill implies that care for children and their
      families can improve when family-centered practices are implemented in health
      care settings.

PMID- 8159497
TI  - One institution's effort to implement family-centered care.
AB  - A children's hospital in the midwest initiated widespread changes in care
      delivery to provide care that is truly family-centered in practice. The role of
      nurses, from nursing administration to the staff nurse level, has been a key
      element in initiating and implementing the institution's move to family-centered
      care. A Family Advisory Council, composed of hospital personnel and families,
      identifies family needs and recommends new programs and approaches. Participants
      in a nursing leadership retreat designated family-centered care as a priority and
      piloted several innovative programs. Nursing commitment has encouraged other
      disciplines and departments to initiate family-centered practices as well.

PMID- 8159498
TI  - Family-centered care at home for families with children who are technology
      dependent.
AB  - The philosophy of family-centered care recognizes parents as equal in
      partnerships with professionals. An adapted nursing process can provide a useful
      mechanism for members of this partnership to create and maintain a system that
      promotes an optimal quality of life at home for children who are technology
      dependent and their families. A family-centered assessment requires the nurse to
      facilitate the family's self-assessment and promote a family systems perspective.
      The family and the nurse together develop a plan of care, with the family
      establishing priorities. The nurse assumes joint responsibility with the family
      in implementing the plan of care, and promotes the principle of normalization and
      the use of informal options whenever possible. Evaluation is formal, informal,
      and ongoing and includes the family and nurse's evaluation of both outcome and
      process.

PMID- 8159499
TI  - Children's illness concepts: old and new paradigms.
AB  - Determining what children know and are able to comprehend about illness is an
      important component of clinical care. This article reviews and critiques the
      cognitive and developmental approach to children's illness concepts and proposes
      an alternative paradigm. The author discusses the expert/novice model and
      methodology and its implications for education and clinical interventions.

PMID- 8159500
TI  - The couple choosing private infant adoption.
AB  - Couples who adopt infants privately face unique problems and issues. Many of
      these problems are related to the adoptive process. During the adoption process,
      nurses may be called upon to play some role related to assisting adoptive
      parents. Nurses can assist these adoptive parents by learning about the process
      and supporting the couple before and after they receive their infant.

PMID- 8159502
TI  - Pediatric management problems. Femoral fracture due to child abuse.

PMID- 8159501
TI  - Enhancing communication with the Passy-Muir valve.
AB  - The Passy-Muir Valve is a speaking valve. It is one alternative for enhancing
      communication skills in children with long-term tracheostomies. As this
      population of children continues to grow, nurses must have an awareness of
      interventions that can promote language development.

PMID- 8159503
TI  - Caring for pediatric patients with HIV: personal concerns and ethical dilemmas.
AB  - An informal survey was conducted to determine nurses' professional and personal
      concerns related to caring for pediatric patients with HIV. Thirty registered
      nurses participated by responding to written open-ended questions. Risk of
      exposure in the workplace and fear of transmission to self or family are examples
      of the issues raised. Many phrased their responses as ethical dilemmas related to
      the principles of beneficence, nonmaleficence, justice, autonomy, veracity, and
      privacy/confidentiality. A bioethics consultant's view of many of the issues
      discussed will immediately follow this article.

PMID- 8159504
TI  - Managing asthma triggers in school.
AB  - Asthma, a costly, common chronic condition, needs to be managed proactively
      rather than reactively. Nurses need to teach children and parents how to
      recognize and avoid asthma triggers. Asthma management is improved when nurses
      communicate with the child, parents, and school personnel.

PMID- 8159505
TI  - A pediatric Trach Card: transforming research into practice.
AB  - Nursing literature has advocated a change in the traditional "resistance" method
      of suctioning artificial airways in children to a shallow suctioning technique.
      This article critiques previous attempts at operationalizing the procedural
      changes and offers a practical, cost-effective tool--the "Trach Card"--to change
      clinical practice.

PMID- 8159506
TI  - Weight comparisons of infants with complete cleft lip and palate.
AB  - PURPOSE: To evaluate the success of the Enlarge, Stimulate, Swallow, Rest (ESSR)
      feeding method for infants with complete cleft lip and palate. METHOD: Sixty-nine
      infants comprised of two groups: an ESSR group and a control group. Paired t
      tests compared mean weights at birth and time of surgery according to feeding
      method. RESULTS: Infants fed by ESSR method showed greater mean weight gain.
      CONCLUSIONS: The ESSR method appeared to be successful in promoting weight gain.

PMID- 8159507
TI  - Conclusions regarding First Temp are questioned.

PMID- 8159508
TI  - Cisapride.

PMID- 8159509
TI  - Proceedings of a round table on current issues in pediatric ear, nose and throat
      infections. Versailles, France, March 25-27, 1993.

PMID- 8159510
TI  - Rationale for antibiotic therapy in pediatric ear, nose and throat infections:
      immunologic issues.

PMID- 8159511
TI  - Otitis media: etiology and diagnosis.

PMID- 8159513
TI  - Medical sequelae and complications of acute otitis media.

PMID- 8159512
TI  - Assessing the treatment alternatives for acute otitis media.

PMID- 8159514
TI  - Surgical management of otitis media.

PMID- 8159515
TI  - Behavior problems in otitis media.

PMID- 8159517
TI  - Childhood sinusitis: pathophysiology, diagnosis and treatment.

PMID- 8159516
TI  - Current issues in upper respiratory tract infections in infants and children:
      rationale for antibacterial therapy.
AB  - Otitis media is a common infection in preschool-age children, but selected
      children have recurrent and severe disease. The characteristics of these children
      include a first episode of infection at an early age, sibling(s) with a history
      of ear infections, a history of not having been breast-fed, attending group day
      care and living in a household with exposure to cigarette smoke. The organisms
      responsible for otitis media are consistently the pneumococcus, H. influenzae
      and, in some areas, M. catarrhalis. Changes in antimicrobial susceptibility and
      differences in virulence govern the choice of antimicrobial agents. Although many
      drugs have clinical efficacy in children with AOM, the choice of optimal agents
      should be based on knowledge of microbiologic efficacy against the major
      pathogens, dosage schedules, side effects, palatability and cost. Sinusitis
      shares with otitis media similar pathogenesis, microbiology and choices of
      antimicrobial drugs for treatment. Although there are fewer data on epidemiology
      and microbiologic efficacy available for sinusitis than for otitis media,
      antibiotics are important for the clinical improvement and eradication of the
      bacterial pathogen from the infected sinus. Group A streptococcal infections are
      an increasing cause of concern because of reports of outbreaks of rheumatic fever
      in some cities in the United States and fatal or severe invasive infections and
      toxin-associated disease. Although Group A streptococci remain susceptible to
      penicillins and cephalosporins, higher rates of eradication of the organism from
      the pharynx by cephalosporins or by macrolides compared with penicillin have
      raised doubt as to the continued consideration of penicillin as the drug or
      choice for patients with streptococcal pharyngitis in communities with high
      incidence of supperative or nonsupperative disease.

PMID- 8159518
TI  - Bacterial sinusitis: etiology and surgical management.

PMID- 8159519
TI  - Reasons for failures in penicillin treatment of streptococcal tonsillitis and
      possible alternatives.

PMID- 8159520
TI  - Complications of streptococcal pharyngitis.

PMID- 8159521
TI  - Role of adenotonsillectomy in the management of pediatric ear, nose and throat
      infections.
AB  - Tonsil and adenoid diseases in children continue to result in considerable
      morbidity despite the age of antibiotics. Immunologic studies have thus far shown
      no adverse effects as a result of adenoidectomy or tonsillectomy. However,
      because the indications for surgery remain controversial, each child must be
      considered on a case-by-case basis.

PMID- 8159522
TI  - Antibiotic resistance of microorganisms involved in ear, nose and throat
      infections.

PMID- 8159523
TI  - Careering ahead.

PMID- 8159524
TI  - New-born crisis.

PMID- 8159526
TI  - The vital ingredient.

PMID- 8159525
TI  - Learning to listen. Interview by Lynn Eaton.

PMID- 8159527
TI  - Mental health. Making women mad.

PMID- 8159528
TI  - Mental health. In the same boat?

PMID- 8159529
TI  - Mental health. Bitter lessons.

PMID- 8159530
TI  - Heartfelt advice.

PMID- 8159531
TI  - The quality of nursing.

PMID- 8159532
TI  - Profiles make perfect practice.

PMID- 8159533
TI  - Alternative medicine. Keeping the doctor away.

PMID- 8159535
TI  - Stress. Changing your mind.

PMID- 8159534
TI  - Alternative medicine. Remedial action.

PMID- 8159536
TI  - Unhappy returners.

PMID- 8159538
TI  - Computing. What's your number.

PMID- 8159537
TI  - Computing. How do you compare?

PMID- 8159539
TI  - Teaching and learning in practice. 7. Assessment in learning (i). Understanding
      assessment issues (continuing education credit).

PMID- 8159540
TI  - Professional development. Breaking bad news: the role of the nurse (continuing
      education credit).

PMID- 8159541
TI  - From Burford and Beeson to Byron.

PMID- 8159543
TI  - Dual purpose.

PMID- 8159542
TI  - Community shortfall.

PMID- 8159544
TI  - Water birth. Water work.

PMID- 8159545
TI  - Water birth. Safety first.

PMID- 8159546
TI  - The family. Out in the cold.

PMID- 8159547
TI  - Trimmed for action?

PMID- 8159549
TI  - Tartan flair. Interview by Tricia Reid.

PMID- 8159548
TI  - Primary nursing. Understanding change.

PMID- 8159550
TI  - Complementary medicine. Healing hands.

PMID- 8159551
TI  - Poor share options.

PMID- 8159552
TI  - Teaching and learning in practice. 7. Assessment in learning (ii). Assessment and
      learning outcomes (continuing education credit).

PMID- 8159553
TI  - Professional development. Breaking bad news: revision notes (continuing education
      credit).

PMID- 8159554
TI  - A confidence betrayed.

PMID- 8159555
TI  - The cost of change.

PMID- 8159556
TI  - In sickness or in health?

PMID- 8159557
TI  - Post-traumatic stress disorder. After the crisis.

PMID- 8159558
TI  - Post-traumatic stress disorder. Borne under stress.

PMID- 8159559
TI  - Post-traumatic stress disorder. Permission to mourn.

PMID- 8159560
TI  - Midwifery. Taking over.

PMID- 8159562
TI  - Celtic concerns.

PMID- 8159561
TI  - Good questions.

PMID- 8159563
TI  - Pension rights and wrongs.

PMID- 8159564
TI  - Personal finance. Many happy returns.

PMID- 8159565
TI  - Balancing the books.

PMID- 8159566
TI  - Learning disabilities. Focal point.

PMID- 8159567
TI  - Learning disabilities. Primary planning.

PMID- 8159568
TI  - Learning disabilities. No specialists needed?

PMID- 8159569
TI  - Nursing: caring or codependent?
AB  - Can nurses practice caring within a healthcare system that promotes codependency?
      Caring promotes mutual empowerment of all participants while codependent caring
      disempowers. Nurses are expected to practice caring with clients, The authors
      contend, however, that nursing, as historically and currently practiced within
      bureaucratic/patriarchal organizations, is founded on a value system that fosters
      codependency. Until nursing is practiced within the context of caring
      organizations and a caring healthcare system, nurses will continue to be
      powerless to shape their own practice as carers and burnout will continue to be a
      problem.

PMID- 8159570
TI  - Practicing invasive procedures on students and patients: an ethical dilemma in
      nursing education.
AB  - Clinical teaching of nursing students has long been an integral part of the
      educational process for nurses. Because invasive procedures encompass complex
      nursing techniques usually performed by the professional nurse, teaching of these
      important skills seems essential. The author discusses the best and safest method
      to teach invasive clinical nursing skills to nursing students.

PMID- 8159572
TI  - Hope, courage, fun.

PMID- 8159571
TI  - Should age be a criterion for rationing health care?
AB  - The need to decrease healthcare costs is urgent. One method of decreasing costs
      that has been proposed is age-based rationing. With the burgeoning number of
      Americans over 65 comes increased spending for health care. It is thought by some
      that this increase represents disproportionate spending, and that the money
      should be spent on health care for the young. Another school of thought is that
      the elderly have a right to health care just as any other group. The author
      believes that age may have to be one consideration for allocation of resources
      but not the only one.

PMID- 8159573
TI  - Poetry in leadership: an enhancer of relationships.
AB  - Nursing is multidimensional, interactive, interdisciplinary, and complex. Almost
      anything that can be said about nursing can be said another way. Some things
      worth being said and heard will not follow the norms of journal presentation. A
      forum accommodates the emerging voice, the new format, the innovative approach.
      Nursing Forum, in an effort to honor the "independent voice" in nursing, presents
      here the voice who elects to enter the dialogue, but who does so "in another
      way."

PMID- 8159574
TI  - Setting aside gender.

PMID- 8159575
TI  - Moral agency in nursing.
AB  - Moral agency involves risk. It is an action that is at odds with the traditional
      role of the nurse. However, as nurses assume more responsibility and
      accountability for client management and outcomes in an increasingly complex and
      uncertain environment, it is essential to approach ethical dilemmas in a manner
      consistent with the caring component of nursing. Case examples are utilized to
      illustrate the attributes necessary for nurses to fulfill their obligations in
      their nurse-client relationships.

PMID- 8159576
TI  - [Etiopathogenesis of hand syndactyly in the light of several experimental
      findings].
AB  - The limb developmental program is comprised of processes of cell multiplication
      and of cell determination, differentiation and morphogenesis. Many of these
      processes depend on cell-cell communications within tissues and between different
      tissue types. The Authors present a review of the more significant data about the
      etiology of the syndactylies of the hand, both in their physiopathogenic aspects
      and in their clinical typology. The peculiarity of these malformations is
      outlined, supported by literature data and personal experimental experiences.

PMID- 8159577
TI  - [Celiac disease and the evolution of its diagnosis. Comparison and experience at
      a hospital pediatric department (1975-1993). (Second part)].
AB  - In a period of over 18 years the prominent medical bibliographic marks with
      regard to definition, diagnosis and examinations of coeliac disease (CD) have
      been compared and as far as possible reproduced. The results confirm the remarks
      derivating from wider statistics. From the beginning of 1975 to the first six
      months of 1993 in Merate Hospital Pediatric Division, 323 patients were submitted
      to a first jejunal peroral biopsy in 133 cases (41.2%) CD was diagnosed. Since 34
      children (25.6%) concluded the ESPGAN diagnostic iter with 3 consecutive
      biopsies, the reasons why the other patients didn't finish or respect the
      programs are here examined. Since 1987 a specific anti-gliadin (IgA and IgG)
      antibodies titrimetry has been available either in the investigation of suspect
      symptomatology or like control mark during the assessment or after a sure CD
      diagnosis. Since october 1992 antiendomysium antibodies (EMA or AEA IgA) have
      been determined only in selected patients. From the examination of 24 subjects
      now checked with AGA IgA/IgG and EMA and with a first positive biopsy, it is
      possible to point out that only one jejunal biopsy (or at the most a second one
      as a control during the gluten challenge) with the guarantee of haematologic
      patterns doesn't raise doubts about a CD diagnosis. Analogous considerations
      mainly refer to the atypical CD "late onset" when a constant lack of AGA and EMA
      during gluten free diet (GFD) or their changes in a non compliance or in gluten
      challenge, can exclude a following hystological confirmation. By this experience
      it follows that a specific antigliadin and antiendomysium antibodies
      investigation is indispensable to the shortening of diagnostic times, to the
      reduction of an often unwelcome invasive diagnostic method and to the discovery
      of the "CD iceberg".

PMID- 8159578
TI  - [Atrial natriuretic factor in normal newborn infants and its effects on kidney
      function in anoxic syndrome and respiratory distress].
AB  - The Authors have studied 26 newborns suffering from anossic syndrome and/or
      respiratory distress. In them are valued as well as the renal function, also the
      behaviour of atrial natriuretic factor (F.A.N.). As a group of control 25 healthy
      and to term newborns were studied. In all subjects studied, but more specifically
      in the anossic, it became evident a net increase of F.A.N., which however was
      within the normal ranges about the 15th year of life. The Authors conclude that
      in normal newborn this behaviour of F.A.N. reflects the important circulation
      modification which is certified after birth, whereas in pathological newborns, in
      whom 69% of cases a functional renal failure is present, the increase of F.A.N.
      is not without significance in the shortening of time of re-establishment of
      renal function.

PMID- 8159579
TI  - [Pregnancy and breastfeeding].
AB  - Several Authors, confronting the mother-child relationship during pregnancy and
      breast-feeding, talk about an uterine an extra-uterine symbiosis. In this way,
      one bypasses the fact that the so called unions end with the processes of
      separation constituted by the partiurition/birth [by the termination, that is to
      say, of the first maternal nurturing (that of placenta), as well as by the
      termination of the second maternal nurturing (that of the individual breast
      feedings)]. The attentive observation of these unions demonstrates that they
      coexist and they imply equilibrium through the processes of separation that not
      only allow a partial autonomy of the developments of mother and child, but also
      make room for the detachments represented by the parturition/birth and by the end
      of the individual breast feedings. The Author is trying to illustrate some
      physiological and pathological equilibriums between these tendencies towards
      reciprocal dependence and reciprocal mother-child autonomy.

PMID- 8159580
TI  - [Osteochondrodysplasia: nosologic assessment and report of 6 clinical cases].
AB  - Osteochondrodysplasias represent an important group of disease affecting
      cartilage and/or bone. The clinical evidence of disarmoniuous low stature, of a
      disproportion between trunk and limbs length, of a big skull can suggest this
      diagnosis and the necessity to carry out all the instrumental investigations. The
      diagnostic suspect can be placed, some time, already in the neonatal period. The
      complexity of problems regarding the osteochondrodysplasias bearer child and his
      family requires a multidisciplinary approach. The Authors present a personal
      experience of six cases of osteochondrodysplasias observed in a period of fifteen
      years.

PMID- 8159581
TI  - [Minor skull trauma in pediatrics].
AB  - Our experience, as well as the latest literature in the field, stresses the
      importance of the clinical and neurological examinations in cases of minor head
      injury. This could avoid the performance of unnecessary imaging and EEG studies
      and the admittance of children who only need pharmacological therapy in order to
      relieve the neurotoxic effects of trauma at the axonal and cellular levels.

PMID- 8159582
TI  - [Magnesium in the prophylaxis of primary headache and other periodic disorders in
      children].
AB  - Migraine has been recently defined a "central neuronal hyperexcitability state",
      maybe magnesium-dependent, and magnesium has been occasionally employed in the
      therapy of adult migraine. The Authors, on the basis of their personal experience
      (previous electromyographic studies), consider childhood migraine and periodic
      syndrome as a clinical equivalent of spasmophilia, in which an intracellular
      deficit of magnesium has been demonstrated, and have employed a magnesium salt in
      the prophylaxis of childhood migraine and migraine equivalents. 40 children with
      periodic syndrome (17 M and 23 F, aged 10.4 +/- 2.9 years) have been treated with
      magnesium pidolate, with doses ranging from 1.5 g/die to 4.5 g/die (corresponding
      to 122-366 mg Mg++):25 of them presented migraine as the main symptom, 12
      recurrent abdominal pain, 3 fever of unknown origin, along with many other
      periodic symptoms. The first control visits have been done at 1 month, clinical
      follow-up lasted a mean period of 6.1 months. Therapy was stopped at 1 month
      visit if ineffective (of some other drug was added); otherwise, magnesium therapy
      was continued with the same dosage for another month, then gradually reduced.
      Clinical response was considered good if crises ceased completely or their
      frequency was reduced to less than 33%; partial if reduced to less than 67% of
      previous incidence; absent if only slightly or not at all reduced. Clinical
      response was good in 72.5% of cases at 1 month, in 77.5% later; partial in 12.5%
      and 10%; absent in 15% and 12.5% respectively. No side effects were observed. The
      compliance of children and their families was complete.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8159583
TI  - [Distribution of new cases of insulin-dependent diabetes mellitus (IDDM) by age,
      sex, seasonality, and clinical characteristics at onset in youngsters from the
      Friuli Venezia Giulia region from 1987 to 1990].
AB  - A retrospective study was undertaken to estimate the incidence of insulin
      dependent diabetes mellitus (IDDM) in youngs (< 18 years) in a North-East
      Province of Italy: Friuli Venezia Giulia (total population: 1,211,320; under age
      18: 185,860). On the assumption that all children with newly detected IDDM are
      referred to a hospital, data were collected from all pediatric departments (14)
      and from all diabetologic services (14) of the Province. A central register for
      all patients receiving drug reimbursement was used as the secondary source for
      validation of case ascertainment, that was 98%. All IDDM cases diagnosed between
      1987 and 1990, with age onset < 18 years, and using insulin at discharge from
      hospital, were included. 73 new IDDM cases under 18 years (47 M, 26 F) were
      observed during the considered period. The average annual incidence of the
      disease (based on first hospital admission) was estimated to be 9.8 per 100,000
      children under 18 years. There was a significantly higher incidence for boys
      (12.6/100,000) than for girls (6.9/100,000). The highest incidence (12.5/100,000)
      was in the age group 10-15, and the lowest (7.2/100,000) in the aged 0-5 years.
      First admission rates showed seasonal variations, with peaks in Oct/Nov and
      Jan/Feb. History of an infection during the month before the first admission was
      present in 17/73 cases. Duration of symptoms < 15 days, 15-30 days, > 30 days,
      was present in 43, 18, 12 patients respectively. Weight loss < 5% was present in
      31/73 cases. Ketoacidosis at onset (pH < 7.36) was present in 30/73
      cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159584
TI  - [Intestinal resection in children: personal experience and suggested follow-up.
      Preliminary results].
AB  - In the paediatric field cases of patients subjected to massive intestinal
      resection (M.I.R.) are more and more frequent; this survival of individuals with
      a small intestine shorter than 30 centimeters is not to be considered
      exceptional. Without going as far as such extreme limits of short residual
      intestine, intestinal resections contributed to create a new pathology
      represented by those patients who, once they have been subjected to particularly
      extended intestinal resections, need a particularly responsible nutritional
      therapy, sometimes with very long hospitalizations. The present study is to
      appraise the nutritional parameters and the residual absorption capacity of a
      group of patients in pediatric age subjected to intestinal resection, in order to
      draw up a record enabling to monitor, as time goes on, the intestinal
      functionality of those patients and to observe as early as possible the
      consequences of an alteration of intestinal physiology while creating the
      premisis for appropriate measures of nutritional supplementing.

PMID- 8159585
TI  - [Massive intestinal resection in the newborn: nutritional and feeding problems].
AB  - Authors present their experience about nutritional treatment of short bowel
      syndrome in newborns. Their results seem to demonstrate that right approach to
      this problem is to start enteral nutrition as soon as possible, using mainly
      human milk and polimeric nutritional solutions. There are several experimental
      evidences that this kind of nutritional approach promote intestinal adaptation
      following massive intestinal resections.

PMID- 8159586
TI  - [Mesenteric lymphangioma: report of a case].
AB  - Lymphangiomas are benign tumours that appears to arise from congenital
      malformation of the lymphatics. They are most commonly reported in the head and
      neck regions. The clinical presentation, diagnosis and treatment of a rare case
      of mesenteric lymphangiomas are reviewed. Ultrasound and computed tomography are
      most useful in the intraabdominal cystic lesions for confirming the diagnosis.
      Intestinal and mesenteric resection, as soon as diagnosis is established, is the
      procedure of choice and results in an excellent outcome.

PMID- 8159587
TI  - [True hermaphroditism in crossed testicular ectopy: report of a case].
AB  - Crossed testicular ectopia is a congenital anomaly characterized by the presence
      of both testes in the same hemiscrotum and may be associated in 20% of the cases
      with genitourinary developmental abnormalities. This review underscores the
      complexities of assessment and surgical management of an uncommon case in which
      crossed testicular ectopia and true hermaphroditism are simultaneously described.

PMID- 8159588
TI  - [Diagnostic problems in a 7-month-old boy with tubercular lobitis].
AB  - A 7-month child with pulmonary tuberculosis infection involving the whole right
      upper lobe is described. He was referred to us after diagnosis of recurrent
      asthmatic bronchitis. In spite of the severity of bronchopulmonary involvement,
      the outcome was good after 5 months of antitubercular chemotherapy.

PMID- 8159589
TI  - [Chronic therapy with ursodeoxycholic acid in a child with Alagille syndrome].
AB  - The effectiveness of oral bile acid therapy with ursodeoxycholic acid (10
      mg/kg/day) was investigated in a 10 year old boy affected by Alagille's Syndrome,
      a chronic cholestatic disorder due to congenital hypoplasia of the intrahepatic
      biliary ducts. Cholestatic and hepatonecrotic indices were measured before and
      during ursodeoxycholic acid therapy and 1 month after stopping and 36 months
      after restarting the treatment. Ursodeoxycholic acid led to a marked improvement
      in the cholestatic and hepatonecrotic parameters which was maintained during all
      the treatment phase. Pruritus and steatorrhea disappeared during the treatment
      with ursodeoxycholic acid. Histological examination of the liver biopsy after the
      treatment revealed a disappearance of the biliary plugs but without increasing he
      intrahepatic bile ducts. The results suggest that ursodeoxycholic acid may
      improve the condition of the children affected by Alagille's Syndrome, specially
      when the liver transplantation is required, and indicate a need for long term
      studies in a larger number of patients.

PMID- 8159590
TI  - [Fetal alcoholic syndrome: a clinical case].
AB  - Fetal alcohol Syndrome (FAS) is a well recognized pattern of malformations,
      produced by a heavy and chronic intake of ethanol during pregnancy. The Authors
      report a clinical case of FAS, observed during an epidemiological study on
      alcohol abuse of pregnancy women. They describe the anomalies and malformations
      of a newborn by a heavy drinking mother, and of his seven year old brother.
      Finally, the Authors consider the toxicological and preventive aspects of
      problem: counselling women of child-bearing age to the dangers of alcoholic
      intake during the gestation period is a professional responsibility.

PMID- 8159591
TI  - [Lyme disease in central Italy. Description of a case of a 3-year-old girl].
AB  - The Authors describe a case of Lyme disease in a 3 year old child who lives in
      the center of Italy, in the Rome area. In this report it has been underlined the
      presence of Lyme disease also in central Italy and the importance of early
      diagnosis and therapy in order to prevent severe complications.

PMID- 8159592
TI  - [A case of persistent fever].
AB  - The Authors report a case of difficult diagnosis, clinically characterised by
      long-term persistent fever. Clinical and laboratory tests led to a first
      conclusion of a tubercular infection; later of a perisplenic hematoma and the
      persistence of high inflammatory indices directed to a different diagnosis.

PMID- 8159593
TI  - Accumulation of clarithromycin in macrophages infected with Mycobacterium avium.
AB  - Clarithromycin is known to accumulate in polymorphonuclear leukocytes, but no
      accumulation studies with macrophages have been reported. We exposed J774
      macrophages, grown for 4-6 days, to clarithromycin 3.0 micrograms/ml for 2 hours.
      The cells were separated from the extracellular fluid, and the concentration of
      clarithromycin was determined in an agar diffusion bioassay. The accumulation of
      clarithromycin was 15.8-fold greater in the cells than it was in the
      extracellular fluid when the test was performed with noninfected cells, and 17.3
      fold greater for cells infected with Mycobacterium avium. However, the ratio was
      substantially lower, only 3.7 for dead macrophages, suggesting that intracellular
      accumulation is probably an active process. These data may clarify the nature of
      the activity of clarithromycin against M. avium in macrophages.

PMID- 8159594
TI  - Pharmacokinetic evaluation of a new oral cyclosporine formulation.
AB  - STUDY OBJECTIVE: To compare the pharmacokinetics of a new oral cyclosporine
      preparation with those of cyclosporine solution diluted in Isocal and the
      intravenous formulation. DESIGN: Randomized, crossover trial. SETTING: Tertiary
      care referral center. PATIENTS: Seven pediatric liver transplant recipients who
      were receiving oral cyclosporine as part of their immunosuppressive regimen. All
      patients completed the study. INTERVENTIONS: Pharmacokinetic studies were
      performed with the intravenous and oral dosage forms. Patients received one dose
      of intravenous cyclosporine, and then were randomized to receive their usual oral
      cyclosporine dose incorporated into a chocolate wafer or mixed with Isocal. After
      a minimum of 3 days, the alternative preparation was administered. Serial
      cyclosporine blood samples were collected at predetermined intervals for 12 hours
      after the third dose for each regimen. Concentrations were determined by high
      performance liquid chromatography. The data for the three dosage forms were fit
      simultaneously with a two-compartment model. MEASUREMENTS AND MAIN RESULTS: No
      difference was seen in F, ka, Cmax, and tmax between the two oral cyclosporine
      preparations (p > 0.05). No new rejection episodes occurred during the study
      period. CONCLUSIONS: We conclude there is no difference in the bioavailability of
      the oral solution and the chocolate formulation. We believe the new preparation
      may increase patient compliance and ensure administration of a complete dose
      compared with the currently marketed solution.

PMID- 8159595
TI  - Cortisol pharmacodynamic response to long-term methylprednisolone in renal
      transplant recipients.
AB  - STUDY OBJECTIVE: To examine the pharmacodynamic patterns of cortisol and
      pharmacokinetic values of long-term methylprednisolone in renal transplant
      recipients. DESIGN: Twenty-four-hour pharmacokinetic and pharmacodynamic
      evaluation of patients who participated in a glucocorticoid-monitoring program.
      SETTING: University-based renal transplant clinic. PATIENTS: Fourteen renal
      transplant recipients studied during a clinically stable period. INTERVENTIONS:
      The daily oral methylprednisolone dose for each patient was administered
      intravenously, and serial plasma cortisol and methylprednisolone samples were
      obtained over 24 hours. MEASUREMENTS AND MAIN RESULTS: Methylprednisolone was
      analyzed by high-performance liquid chromatography. The baseline morning cortisol
      serum concentrations ranged from 9.8-210.7 ng/ml. After the drug was
      administered, cortisol declined in a linear fashion with a mean suppression half
      life of 2.4 +/- 0.9 hours. The cortisol nadir was reached at 12-16 hours in 11 of
      14 patients. The return cortisol area under the curve (AUC-Cret) was noted in all
      patients and ranged from 57-987 ng.hr/ml. The total cortisol area under the curve
      was greater in patients who had been transplanted for longer than 2 years (1676
      +/- 252 vs 836 +/- 405 ng.hr/ml; p < 0.05) compared with more recently
      transplanted patients. Methylprednisolone clearance ranged from 100-1181 ml/hr/kg
      with a mean volume of distribution of 1.3 +/- 0.6 L/kg. The methylprednisolone
      half-life ranged from 1.2-4.7 hours. The correlation between AUC-Cret and
      methylprednisolone AUC was -0.64 (p < 0.05). CONCLUSIONS: The pharmacodynamic
      response of cortisol in renal transplant recipients may be associated in part
      with long-term steroid exposure. However, the interrelationship between the
      endocrine and immune system may also affect cortisol's disposition and subsequent
      recovery patterns in this population. Considerable interpatient variability was
      apparent in both the cortisol pharmacodynamic response as well as the
      pharmacokinetics of methylprednisolone. These findings suggest a more
      individualized dosing method may be necessary to optimize the immunosuppressive
      effect of glucocorticoids and minimize clinical toxicity.

PMID- 8159596
TI  - Angioedema and urticaria associated with omeprazole confirmed by drug
      rechallenge.
AB  - Omeprazole is a substituted benzimidazole that has gained widespread use in the
      treatment of acidic and peptic ulcer disease. Adverse events with the drug are
      rare and involve mainly the gastrointestinal and central nervous systems. Skin
      inflammation, urticaria, pruritus, alopecia, and dry skin have been reported in
      0.5-1.5% of patients. To date, no published report has linked angioedema with
      omeprazole. We report a case of a 34-year-old woman with cellulitis, ulcerative
      erosive esophagitis, and gastric and duodenal ulcers who developed several
      hypersensitivity reactions characterized by shortness of breath, wheezing, cough,
      mild angioedema, and total body urticaria and pruritus. These symptoms correlated
      with the addition of omeprazole to her regimen and the timing of its
      administration. A previous case report prompted a rechallenge with enteric-coated
      omeprazole granules removed from the capsule shell. Recurrence of the adverse
      events suggested an allergy to the drug itself and not the capsule. Angioedema
      can be a life-threatening allergic reaction requiring immediate treatment.
      Rechallenge using omeprazole with or without the capsule shell should be done
      only in a hospital setting where prompt action can be taken in the event of an
      emergency.

PMID- 8159597
TI  - Febrile reaction associated with urokinase.
AB  - Urokinase is an endogenously produced human proteolytic enzyme used to treat many
      thrombotic disorders. A 54-year-old man with recurrent myocardial infarction
      experienced fever during intracoronary urokinase infusion into a saphenous vein
      graft; the fever resolved after discontinuation of the infusion. After excluding
      all other possible etiologies of fever, urokinase was determined to be the cause.
      Several studies indicated that this reaction may be associated with urokinase
      infusion, but it is actually recognized by few individuals. This is the first
      published case report of the adverse event to our knowledge.

PMID- 8159598
TI  - Red-top tubes do not displace drug from protein-binding sites.

PMID- 8159599
TI  - Effect of human serum on killing activity of vancomycin and teicoplanin against
      Staphylococcus aureus.
AB  - STUDY OBJECTIVE: To investigate the effects of pooled human serum (PHS) on the
      killing activity of vancomycin and teicoplanin against two isolates of
      Staphylococcus aureus from patients treated for endocarditis. DESIGN: An in vitro
      assessment of antibiotic susceptibility and killing rates. SETTING: An urban
      university teaching hospital. PATIENTS: Pooled human serum from patients treated
      for endocarditis. INTERVENTIONS: Two clinical isolates of Staphylococcus aureus
      were obtained from patients treated for endocarditis. Media consisted of cation
      supplemented Mueller-Hinton broth alone and in 1:1 dilutions with PHS, 2-hour
      heat-inactivated PHS (HI-PHS), ultrafiltrate (UF), and 2-hour heat-inactivated
      ultrafiltrate (HI-UF). Heat inactivation of PHS and UF was accomplished by
      treatment at 56 degrees C for 2 hours. MEASUREMENTS AND MAIN RESULTS: Killing
      curves with vancomycin and teicoplanin were performed using drug concentrations
      of 45 micrograms/ml and a starting inoculum of approximately 1 x 10(6) colony
      forming units (cfu)/ml. Bactericidal rates (-log cfu/ml/hr) were calculated from
      the slope of the killing curves over 0-12 hours (mean 3-8 replicates).
      CONCLUSIONS: The killing activity of vancomycin in PHS and HI-PHS against both
      isolates was significantly greater than all other media tested (p < 0.0001).
      Ultrafiltrate tended to reverse this enhancement effect. Addition of PHS or UF
      did not enhance teicoplanin's killing activity against either isolate. Further
      investigations in our laboratory will determine if the factor is antibiotic class
      or organism specific.

PMID- 8159600
TI  - Pharmacokinetic evaluation of para-aminosalicylic acid granules.
AB  - STUDY OBJECTIVE: To determine the bioavailability and renal elimination of para
      aminosalicylic acid (PAS) and its inactive metabolite acetyl-para-aminosalicylic
      acid (AcPAS) from a new PAS formulation. DESIGN: (a) Single-dose pharmacokinetic
      study in healthy volunteers; (b) Day-1 and day-8 pharmacokinetic comparison in
      patients with multidrug-resistant tuberculosis (MDR-TB). SETTING: Referral
      hospital that specializes in the treatment of mycobacterial infections. PATIENTS:
      (a) Twelve healthy male and female volunteers recruited by the investigators.
      Eleven subjects (92%) completed the study; one subject could not maintain venous
      access and was removed from the study. (b) Six sequential male and female
      patients receiving multidrug treatment for advanced MDR-TB. All patients
      completed the study. INTERVENTIONS: (a) Volunteers received a single 4-g dose of
      enteric-coated PAS granules administered with food. Blood and urine samples were
      collected over 24 hours after the dose. (b) Patients received 4-g doses of
      enteric-coated PAS granules every 8 hours for 7 days as part of their treatment
      regimen. Blood samples were obtained at approximately 2, 4, and 8 hours after the
      first dose on day 1 and the twenty-second dose on day 8. MEASUREMENTS AND MAIN
      RESULTS: Concentrations of PAS and AcPAS were determined using high-performance
      liquid chromatography. The serum concentration-time curves from volunteers and
      patients showed sustained PAS concentrations, in contrast to immediate-release
      sodium PAS tablets. In the six patients with tuberculosis, day 8 concentrations
      were considerably higher than those on day 1, and all were sustained well above
      the PAS minimal inhibitory concentration for Mycobacterium tuberculosis.
      CONCLUSIONS: Para-aminosalicylic acid granules produce adequate serum
      concentrations and appear to be safe.

PMID- 8159601
TI  - Venous irritation related to intravenous administration of phenytoin versus
      fosphenytoin.
AB  - STUDY OBJECTIVE: To compare the frequency, severity, and time course of venous
      irritation after administration of a single intravenous dose of phenytoin with an
      equimolar dose of fosphenytoin, a water-soluble phenytoin prodrug. DESIGN:
      Randomized, double-blind, two-period, crossover study. SETTING: University
      hospital clinical research unit. PATIENTS: Twelve healthy volunteers within 15%
      of ideal body weight and with no clinically significant abnormalities on physical
      examination, medical history, or laboratory assessment. INTERVENTIONS: Volunteers
      randomly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 ml)
      or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for
      the crossover treatment 14-21 days later. MEASUREMENTS AND MAIN RESULTS: Subjects
      assessed venous irritation (pain, burning, itching), and investigators evaluated
      phlebitis (erythema, swelling, tenderness), induration, exudation, and cording.
      Phenytoin was associated with a significantly higher degree of pain at the
      infusion site in all subjects and a significant degree of phlebitis in eight
      subjects (p < 0.05); cording occurred in six subjects. The time course of
      phenytoin-induced phlebitis was bimodal. Erythema and tenderness were prominent
      at the end of the infusion and again at 24 hours. Cording was first noted between
      24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with
      mild pain in two subjects, one incident of phlebitis, and no erythema or cording.
      CONCLUSIONS: Fosphenytoin administration resulted in significantly less venous
      irritation and phlebitis compared with an equimolar dose of phenytoin. The
      clinical use of this water-soluble phenytoin prodrug should minimize the
      frequency and severity of infusion-site reactions and should allow convenient,
      rapid, intravenous administration of drug, undiluted or admixed with intravenous
      solutions.

PMID- 8159602
TI  - Picenadol in a large multicenter dental pain study.
AB  - STUDY OBJECTIVE: To estimate the analgesic dose of picenadol hydrochloride equal
      to codeine 60 mg in a dental pain model. DESIGN: Randomized, double-blind,
      parallel, dose-response study. SETTING: Four university-based dental clinics.
      PATIENTS: Four hundred eight adult patients with moderate or severe pain after
      extraction of one or more impacted molar teeth plus bone removal. INTERVENTIONS:
      Patients received orally administered single doses of picenadol 15 and 30 mg,
      codeine phosphate 30 and 90 mg, or placebo. METHODS: Single oral doses of
      picenadol 15 and 30 mg, an opioid agonist-antagonist, were compared with codeine
      30 and 90 mg and placebo in 408 patients with moderate or severe pain from third
      molar extraction in a randomized, double-blind, parallel study. Assessments were
      performed for pain intensity, pain relief, and adverse events for up to 6 hours
      after drug administration. MAIN RESULTS: Picenadol 30 mg and codeine 90 mg were
      more effective than placebo based on sum of pain intensity differences, total
      pain relief, peak pain relief, and duration of analgesia (p < 0.05). Compared
      with placebo, the frequency of adverse events was highest for patients receiving
      codeine 90 mg (p < 0.05). No patients discontinued due to adverse events, and all
      such events resolved spontaneously. CONCLUSIONS: Picenadol 22 mg was estimated to
      be equianalgesic to codeine 60 mg, and picenadol 30 mg was safe in this dental
      pain model.

PMID- 8159603
TI  - Hypertension and left ventricular hypertrophy: is drug therapy beneficial?
AB  - Left ventricular hypertrophy (LVH) is a consequence of long-standing hypertension
      and is considered to be an independent risk factor for cardiovascular morbidity
      and mortality. Several antihypertensive agents are capable of inducing regression
      of LVH, but it is not known which class of drugs is most effective. The impact of
      drug-induced reversal of hypertrophy on ventricular function remains a
      controversial issue. Furthermore, the long-term clinical benefits of LVH
      regression have yet to be documented. Controversies also exist regarding the
      clinical outcomes associated with drug-induced LVH regression.

PMID- 8159604
TI  - In vitro evaluation of high-level, gentamicin-resistant enterococci isolated from
      bacteremic patients.
AB  - We attempted to characterize the susceptibility of high-level, gentamicin
      resistant (HLGR, minimum inhibitory concentration [MIC] > 2000 micrograms/ml)
      enterococcal blood isolates and evaluated a small subset of these isolates for
      bactericidal synergy. Thirteen Enterococcus faecalis and three Enterococcus
      faecium isolates that were HLGR were prospectively collected. Standard broth
      macrodilution techniques were used to determine the MICs and minimum bactericidal
      concentrations to a variety of antibiotics. Two isolates were evaluated for
      synergy by time-kill curve methods using combinations of penicillin and
      streptomycin, teicoplanin and rifampin, and vancomycin and ciprofloxacin.
      Teicoplanin was the most active antibiotic tested, with all isolates exhibiting
      susceptibility to this agent. Four E. faecalis isolates and one E. faecium
      isolate expressed only low-level resistance to streptomycin (LLSR, MICs 32-64
      micrograms/ml). Penicillin and streptomycin produced bactericidal synergy in the
      LLSR isolate. The other antibiotic combinations did not result in bactericidal
      synergy in the two isolates tested. For HLGR enterococci that are only LLSR, the
      combination of penicillin-streptomycin appears to provide adequate bactericidal
      activity. Teicoplanin may potentially be useful for streptomycin-resistant HLGR
      isolates.

PMID- 8159606
TI  - The language of pathology.

PMID- 8159605
TI  - An alternative sodium bicarbonate regimen during cardiac arrest and
      cardiopulmonary resuscitation in a canine model.
AB  - We evaluated the effect of frequent, early bolus administration of low-dose
      sodium bicarbonate (NaHCO3) on blood gas values during ventricular fibrillation
      and cardiopulmonary resuscitation (CPR) compared with normal saline and standard
      bolus doses of NaHCO3. This was a randomized laboratory investigation involving
      13 mongrel dogs and 18 experiments (5 dogs were used in a crossover manner). Each
      dog underwent 3 minutes of ventricular fibrillation, followed by 15 minutes of
      CPR. Animals were randomly assigned to one of three treatments administered early
      in the resuscitation effort: NaHCO3 0.5 mEq/kg at 5, 10, and 15 minutes of
      ventricular fibrillation (SB); NaHCO3 1 mEq/kg at 5 minutes and 0.5 mEq/kg at 15
      minutes of fibrillation (SB); or 0.9% NaCl 1 ml/kg at 5 minutes and 0.5 ml/kg at
      15 minutes of fibrillation (P). A total of 15 experiments were included for
      analysis. Arterial and venous blood gases were sampled at 4, 8, 13, and 18
      minutes of fibrillation. The SB group demonstrated the highest arterial partial
      pressures of carbon dioxide (pCO2) at each sampling point after NaHCO3, including
      the 18-minute sample: 42 +/- 12, 29 +/- 11, and 35 +/- 10 torr for SB, P, and B,
      respectively. In addition, SB produced arterial alkalemia (pH > 7.45) after
      NaHCO3 administration. The arterial pH at 18 minutes of fibrillation for SB, P,
      and B was 7.46 +/- 0.14, 7.29 +/- 0.07, and 7.41 +/- 0.1, respectively. Similar
      trends for pCO2 and pH were observed for venous samples.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8159607
TI  - Demonstration of Epstein-Barr viral DNA in paraffin-embedded tissues of Burkitt's
      lymphoma from Argentina using the polymerase chain reaction and in situ
      hybridization.
AB  - Burkitt's lymphoma (BL) is the most frequent non-Hodgkin's lymphoma in children
      in Argentina. Although epidemiologic studies have linked Epstein-Barr virus (EBV)
      to more than 90% of African BL cases but to only 10-20% of American and French
      cases, increased EBV-specific antibody titers were demonstrated in 73% of
      Argentinian patients with BL. To characterize the relationship between EBV and BL
      in Argentina, we analyzed paraffin-embedded tissues from 16 cases of BL for the
      presence of EBV DNA using the polymerase chain reaction (PCR) and in situ
      hybridization (ISH). PCR analysis showed that only 4 of 16 specimens contained
      the EBV BamW fragment, and these specimens were all from cases diagnosed in 1984.
      Results of ISH performed with a specific biotinylated DNA probe against the
      NotI/PstI fragment of EBV correlated with the PCR findings. EBV sequences were
      detected with ISH in 70-90% of the tumor cells from the 4 positive cases. These
      data may suggest an epidemic outbreak of EBV-related BL in 1984 superimposed on
      sporadic cases of BL, for which EBV may not have been an essential factor. This
      study also demonstrates the value of using molecular techniques on archival
      tissue to track epidemiologic trends.

PMID- 8159608
TI  - Malignant solitary fibrous tumor of the pleura.
AB  - We describe a case of malignant solitary fibrous tumor of the pleura in a 15-year
      old female who presented clinically with back pain. Grossly, the tumor had a
      pedicle attached to the pleura and histologically showed proliferating spindle
      shaped cells with a high mitotic index. Immunohistochemical and ultrastructural
      features were consistent with a tumor of fibroblastic origin. Flow cytometric DNA
      analysis revealed an aneuploid population among the tumor cells.

PMID- 8159609
TI  - Extracellular matrix of small round cell tumors of childhood: an
      immunohistochemical study of 67 cases.
AB  - Sixty-seven childhood tumors were studied immunohistochemically for the
      extracellular matrix element type IV collagen, laminin, and fibronectin. Tumors
      included Ewing's sarcoma, primitive neuroectodermal tumor, small cell
      osteosarcoma, neuroblastoma or ganglioneuroblastoma, rhabdomyosarcoma, and
      lymphoma. It was found that small cell osteosarcoma was often positive for
      fibronectin but not type IV collagen or laminin, a new observation. In the
      lymphomas, matrix proteins were rarely found. Ewing's sarcoma was variably
      positive for type IV collagen and laminin, but fibronectin was absent.
      Extracellular laminin and fibronectin were found in one of two cases of primitive
      neuroectodermal tumor. In neuroblastoma and ganglioneuroblastoma, the matrix
      components were rarely found. These results, discrepant with findings in cultured
      cells, may reflect the altered capacity of tumors to produce these proteins in
      vitro, which suggests that caution should be exercised in drawing conclusions
      regarding the nature or histogenesis of tumors from data obtained with cultured
      tumor cells. Embryonal rhabdomyosarcoma frequently contained all matrix elements
      in the extracellular space and in a dotlike pattern in the cytoplasm; alveolar
      rhabdomyosarcoma rarely contained these proteins and never exhibited the dotlike
      pattern. The frequent finding of matrix proteins in embryonal rhabdomyosarcoma
      but only rarely in alveolar rhabdomyosarcoma and the unique immunostaining
      pattern in embryonal rhabdomyosarcoma may prove to be a useful adjunct in the
      diagnosis of childhood tumors.

PMID- 8159610
TI  - Redefinition of the sudden infant death syndrome: the disadvantages.
AB  - For many years the definition of SIDS has been the sudden death of an infant that
      was unexpected by history and in which a thorough postmortem examination failed
      to demonstrate an adequate cause of death. In 1991 a report was published in this
      journal from a panel convened by the NICHD which recommended that the diagnosis
      of SIDS not be made unless a death scene investigation has been conducted. The
      panel recommended further exclusions from the diagnosis of SIDS of certain
      "unresolved" cases. We believe the changes recommended by the NICHD panel are
      impractical and may have a serious negative impact on SIDS research and on the
      surviving family members of the SIDS victims.

PMID- 8159611
TI  - So-called congenital-infantile fibrosarcoma: does it exist and what is it?
AB  - Congenital-infantile fibrosarcoma (CIFS) is a cellular, mitotically active
      neoplasm with a paradoxically limited biologic potential in most cases. Its
      phenotype and proliferative features have been incompletely explored with
      inconclusive results. We studied the clinical, pathologic, immunohistochemical,
      and flow cytometric features of 26 cases (16 males, 10 females; 92% of cases
      detected within the first year life; 11 on extremities, 10 on the trunk, 5 in the
      head and neck). All displayed interlacing fascicles of spindle cells with focal
      necrosis, mitoses, and a focal hemangiopericytomatous vascular pattern.
      Immunohistochemically, 22 of 22 cases were reactive for vimentin. Other markers
      were present in a minority of cases. Flow cytometry of formalin-fixed, paraffin
      embedded tissue in 10 cases demonstrated moderate to high proliferation activity
      and diploid DNA content in nine cases. Follow-up of all 26 patients revealed 20
      patients alive and well, 15 without evidence of recurrence, and 5 with a small
      residual mass. Six patients had died of tumor, none had distant metastases.
      Patients with tumors in the head and neck or deep truncal soft tissues, including
      mesentery, had a poor prognosis because of local extension. CIFS is a clinically
      and morphologically homogeneous condition with considerable immunophenotypic
      diversity. Diploid DNA content in the majority of cases suggests that it may not
      be a fully expressed sarcoma. The clinicopathologic features are sufficiently
      distinctive to permit recognition and warrant conservative initial treatment in
      most cases. "Fibrosarcoma" is a term of convenience rather than of nosologic
      certainty.

PMID- 8159612
TI  - Confined placental mosaicism and stillbirth.
AB  - The cause of stillbirth can usually be determined in only 20% of cases. An
      increased frequency of adverse pregnancy outcome, including pregnancy loss,
      intrauterine growth restriction, and premature labor, has been observed in
      association with confined placental mosaicism (CPM), which is characterized by a
      discrepancy between the karyotype of the fetus and placenta. Specific chromosomal
      trisomies have been observed in CPM more frequently than others, with trisomy of
      chromosomes 7, 16, and 18 being the most prevalent. In pregnancies with CPM it
      has been shown that the zygote is often trisomic, and postzygotic loss of the
      additional chromosome occurred in the embryonic progenitor cells leading to a
      dichotomy between the placenta and the embryo/fetus. In one third of such cases
      fetal uniparental disomy (UPD), which is the presence of both homologues of a
      chromosome derived from one parent, can be expected. The specific role of the
      trisomic placenta and the presence of fetal UPD in cases of altered intrauterine
      fetal development has not been fully established for various chromosomes.
      Therefore, to enhance our understanding of the pathogenesis of stillbirth it is
      imperative that cytogenetic analysis of both fetal and placental tissues be
      performed in all cases of unexplained stillbirth.

PMID- 8159613
TI  - Genomic imprinting: a new mechanism for disease.
AB  - Evidence has been accumulating from various fields of research that genomic
      imprinting, defined as the differential modification of genetic material
      depending on whether inheritance is from the male or female parent, occurs in
      mammals as well as in man. Human genetic diseases such as complete hydatidiform
      moles, triploidy, Prader-Willi syndrome, Angelman syndrome, and various cancers
      provide strong support for the important role of genomic imprinting in human
      development and represents a new mechanism for disease.

PMID- 8159614
TI  - Cytogenetic and molecular analysis of pediatric neoplasms: diagnostic and
      clinical implications.
AB  - Recurring chromosome changes, particularly those closely associated with specific
      subtypes of tumors, have provided critical clues to the location of the genes
      involved in the genesis of these tumors. These, in turn, have led to the cloning
      of these genes, especially those located at translocation breakpoints in
      leukemias, lymphomas, and sarcomas. The immediate consequence of the cloning of
      these genes is to provide DNA probes for various diagnostic tests, including
      standard Southern blot analysis, the polymerase chain reaction, and fluorescence
      in situ hybridization. Because many of these chromosome rearrangements are
      associated with either an improved or a poorer survival, karyotypic abnormalities
      provide prognostic information. In the future, more sophisticated understanding
      of the genes involved and of the nature of their altered function should lead to
      improved therapy.

PMID- 8159615
TI  - Maldescent of the thymus.

PMID- 8159616
TI  - Recurrent hemangiopericytoma of the chest wall: report of a case in a 5-year-old
      boy.
AB  - Hemangiopericytoma in infants and children is usually benign. A case of recurrent
      hemangiopericytoma of the mediastinum in a 5-year-old boy is reported. The tumor
      recurred twice because of incomplete excision in the first instance.
      Immunohistochemistry of this enigmatic tumor is reviewed and ultrastructural
      features are described. The importance of total initial excision of the tumor and
      a prolonged follow-up is highlighted.

PMID- 8159617
TI  - Aggressive angiomyxoma of the vulva in an 11-year-old girl.
AB  - A rare case of aggressive angiomyxoma involving the vulva of an 11-year-old girl
      is reported. The pathologic features that distinguish this lesion from other
      myxoid tumors or tumorlike conditions of the perineum and vulva in children are
      discussed.

PMID- 8159618
TI  - Chest wall hamartoma in infancy: a case report with immunohistochemical analysis
      of various interstitial collagen types.
AB  - We present one case of a chest wall hamartoma diagnosed in a 4-week-old boy. This
      entity is an extremely rare but characteristic congenital malformation of the
      ribs in infancy. To avoid maltreatment, it has to be distinguished from benign
      and malignant neoplasms on the basis of distinct histological features presented
      here. The immunohistochemical localization of various collagen types supports the
      notion of the hamartomatous nature of this lesion.

PMID- 8159619
TI  - Subdermal fibrous hamartoma of infancy: pathology of 40 cases and differential
      diagnosis.
AB  - Forty subdermal fibrous hamartomas of infancy occurred in 29 males and 11 females
      who were 7 months to 4 years of age at surgery. At least 4 were congenital. The
      lesions were situated in axilla, chest wall, and breast (17 cases); abdominal
      wall, inguinal region, and scrotum (8); buttock and lower limb (6); upper limb
      (4); neck and scalp (3); and low back (2). They were 0.7 to 10 cm, ill defined,
      and five underwent reexcision, which was curative in all. All had the
      characteristic mixture of fibrous and adipose tissue and nests of immature
      mesenchyme in different proportions, and nearly all showed lymphocytes and thick
      patent capillaries in the mesenchyme. However, the fibrous component varied
      considerably in amount, pattern, and cellularity, so that lesions that were
      typical in some areas, in others resembled collagenizing vascular granulation
      tissue, deep fibrous histiocytoma, or fibromatosis. Those in which adipose tissue
      predominated were distinguished from fibrolipoma by foci of immature mesenchyme
      and from lipoblastoma by their lack of a capsule and of a lobular pattern.

PMID- 8159620
TI  - Spondylocostal dysostosis with perinatal death and meningomyelocele.
AB  - A preterm black girl was born at 35 weeks of gestation to a healthy
      nonconsanguineous couple. She had a very short trunk with disproportionately long
      extremities, mild prognathism, low-set ears, thoracolumbar meningomyelocele, and
      imperforate anus. She died 45 min after birth. Roentgenograms revealed
      hemivertebrae, block vertebrae, severe thoracic lordosis, absent sacrum,
      posterior fusion of some ribs with greater distance among them in the anterior
      thorax, and relatively long extremities. Internal examination showed an intact
      meningomyelocele extending from the first thoracic vertebra to the lumbosacral
      region, containing 150 mL of clear fluid. The lungs were severely hypoplastic.
      Spondylocostal dysostosis encompasses a spectrum of vertebral abnormalities
      ranging from spina bifida occulta to large meningomyelocele and from mild to
      severe thoracic deformities that produce pulmonary hypoplasia and respiratory
      insufficiency. Our case is one of the most severe ever described.

PMID- 8159621
TI  - Pulmonary hypertension associated with portal hypertension in a child with
      Williams syndrome--a case report.
AB  - A 14-year-old white female with Williams syndrome and portal hypertension
      presented in shock; at autopsy she was found to have grade II to VI vascular
      changes of pulmonary hypertension. This case demonstrates the association of
      portal hypertension and pulmonary hypertension in a pediatric patient.

PMID- 8159622
TI  - Coombs-positive autoimmune hemolytic anemia and postinfantile giant cell
      hepatitis in children.
AB  - We report a 23-month-old girl and a 9-month-old boy who presented with autoimmune
      hemolytic anemia followed by recurrent episodes of severe hepatitis. The first
      episode of hepatitis occurred 1 week and 15 months after presentation,
      respectively. Histologically, the livers showed loss of lobular architecture with
      diffuse giant cell transformation of hepatocytes and portal and pericellular
      fibrosis. The first patient died at 4 1/2 months after her initial presentation
      with a well-established micronodular cirrhosis. The second patient responded to
      steroid therapy and the hepatitis recurred when steroids were tapered.
      Postinfantile giant cell hepatitis may occur in association with Coombs-positive
      hemolytic anemia, it is thought to have an autoimmune mechanism, and early and
      sustained immunosuppression may control the progressive hepatocellular damage and
      prevent cirrhosis.

PMID- 8159623
TI  - P53 protein expression in hepatoblastoma: an immunohistochemical investigation.
AB  - Mutations of the p53 tumor suppressor gene with immunohistochemically detectable
      expression of p53 protein have been described in many different malignant tumors.
      In this study, 12 hepatoblastomas of various subtypes were investigated
      immunohistochemically with a monoclonal antibody for the expression of p53
      protein. Immunoreactivity for p53 protein was found in both small cell tumors
      investigated and in embryonal areas in two out of eight tumors, but not fetal
      (eight tumors) or mesenchymal (four tumors) areas. The findings show that
      immunohistochemically detectable expression of p53 protein, which generally
      indicates mutation of the gene, may also be present in hepatoblastoma. The
      finding of p53 protein immunoreactivity in both of the small cell tumors but none
      of the fetal areas is consistent with a proposal in the literature concerning the
      histogenesis and differentiation of the various subtypes---that fetal
      hepatoblastoma is the most well-differentiated and small cell hepatoblastoma the
      least well-differentiated subtype.

PMID- 8159624
TI  - Labeled lectin studies of renal tubular dysgenesis and renal tubular atrophy of
      postnatal renal ischemia and end-stage kidney disease.
AB  - Renal tubular dysgenesis (RTD), with hypoplasia especially of renal proximal
      convoluted tubules and clinical neonatal anuria or oliguria, has been reported as
      a congenital familial (autosomal recessive) disease, variably with features of
      oligohydramnios, Potter syndrome, or pulmonary hypoplasia. A similar tubular
      lesion due to antenatal tubular atrophy has been reported for conjoined twins
      with twin-twin transfusion syndrome or acardia and in infants of mothers given
      antihypertensive agents, including angiotensin-converting enzyme (ACE)
      inhibitors, during pregnancy, and it has been seen as a unilateral lesion in
      young infants with renal artery stenosis due to arteritis or medial arterial
      calcinosis. The renal tubular changes in RTD are very like those of the
      "endocrine kidney" in experimental animals and resemble those of the renal
      tubular atrophy of end-stage kidney diseases such as glomerulonephritis,
      tubulointerstitial kidney disease, obstructive uropathy/pyelonephritis, graft
      rejection of transplanted kidneys, or the renal parenchymal changes seen with
      protracted dialysis therapy. Labeled lectins that differentially mark proximal
      convoluted, distal convoluted and connecting, and collecting tubules showed no
      distinctive differences in staining patterns of the hypoplastic renal tubules of
      infants and children with RTD, postnatal renal artery obstruction, or the various
      types of end-stage renal disease with the lectins used (PNA, GSLI, UEA, and LTA).
      The findings suggest that the renal tubular changes in some if not all the
      conditions studied are the result of renal ischemia. The reported familial RTD
      with hypernephronic nephromegaly may be a specific disorder, but other forms
      could reflect renal ischemia acquired in utero or in early or later postnatal
      life.

PMID- 8159625
TI  - Acne vulgaris: pathogenesis and management.

PMID- 8159626
TI  - The cephalosporin antibiotics.

PMID- 8159627
TI  - Epstein-Barr virus infection.

PMID- 8159628
TI  - Special records for special conditions--failure to thrive.

PMID- 8159629
TI  - Eating disorders in adolescence.

PMID- 8159630
TI  - The role of peripheral venous nutrition during childhood.

PMID- 8159631
TI  - Effects of chlorhexidine on the isolated rat phrenic nerve-diaphragm preparation.
AB  - Dose-dependent inhibitory effect of chlorhexidine (2.5 x 10(-5)-5.0 x 10(-4) g/ml
      on neuromuscular transmission were localized by tension and electromyogram
      recording during indirect stimulation. Subsequent direct stimulation showed an
      additional inhibition which might be located to the sarcolemma. In addition,
      contracture was observed at the highest concentrations. Microelectrode
      experiments showed a miniature endplate potential frequency increase (at 1.0 x
      10(-6) g/ml), suggesting a presynaptic action. Increasing the dose to 5.0 x 10(
      6) g/ml disclosed a decrease of the miniature endplate potential amplitude,
      indicating a reduction of the postsynaptic receptor sensitivity, which might
      cause neuromuscular inhibition. This was confirmed by endplate potential
      recording in cut preparations. The endplate potential showed a moderate degree of
      use-dependent inhibition which did not usually cause a tetanic fade. Experiments
      with curare, decamethonium and neostigmine indicated that chlorhexidine probably
      caused a decamethonium-like inhibition. A small depolarization of the sarcolemma
      was probably not the cause of the directly elicited inhibition or contracture.
      The contracture was potentiated in preparations made myotonic by pretreatment
      with para-hydroxy-mercuribenzoate. It could not be inhibited by the excitation
      contraction uncoupler dantrolene, but it was dependent on extracellular Ca2+.
      Chlorhexidine-induced influx of Ca2+ might thus cause the contracture.

PMID- 8159632
TI  - Pentamidine accumulates in rat liver lysosomes and inhibits phospholipid
      degradation.
AB  - The subcellular distribution and the effects of pentamidine on the ultrastructure
      of the rat liver were studied. Rats were given single or repeated daily
      intraperitoneal injections of 10, 25 or 50 mg pentamidine isethionate/kg b. wt.
      for 1, 4, 6, 9 or 16 days. The livers were removed for ultrastructural and
      biochemical analyses on the day after termination of each series of injections
      and in addition 7 and 35 days after the 16th injection. Electron microscopy of
      liver tissues showed that the general cellular architecture of the hepatocytes
      was preserved. The subcellular organelles were normal, except for the secondary
      lysosomes, which were severely altered and laden with multilamellar, myelin
      structures (myelin bodies) that gradually increased with dose and time course
      following repeated injections. These altered lysosomes were enriched in
      phospholipids. The alteration of the lysosomes persisted for up to 5 weeks after
      cessation of administration. Pentamidine was highly enriched in the lysosomal
      fraction (30-50 times more than in the liver homogenate). It was calculated that
      the lysosomal pentamidine accounted for practically all pentamidine distributed
      to the liver. The demonstrated accumulation of pentamidine in the lysosomes may
      explain the known large volume of distribution of this drug and may be one
      mechanism for organ toxicity.

PMID- 8159633
TI  - Liposolubility and protein binding of oxycodone in vitro.
AB  - The liposolubility and protein-binding of oxycodone were studied in vitro and
      compared with other opioids. Liposolubility was assessed by three different
      methods: 1) the shake-flask method with n-octanol at pH 4-9, 2) measuring the
      retention time in reversed-phase high-performance liquid chromatography (RP-HPLC)
      with a LiChrosorb RP-18 and 3) studying the solubility in human epidural and
      subcutaneous fat. Human fat was obtained from patients undergoing surgery for
      herniated intervertebral disc. After incubation, pieces of fatty tissue immersed
      in a buffer solution containing oxycodone, morphine, pethidine or fentanyl for 10
      40 min.; tissue pieces were homogenated, opioids extracted and opioid
      concentrations measured by gas- and high-performance liquid chromatography. The
      binding of oxycodone, morphine and fentanyl in plasma proteins was studied by
      ultrafiltration (Amicon-kit). The mean apparent partition coefficients Papp of
      oxycodone, morphine, pethidine and fentanyl in n-octanol at pH 7 were 0.7, 0.5,
      10.5 and 399, respectively. The retention times in RP-HPLC for oxycodone,
      morphine, pethidine, fentanyl and buprenorphine were 0.6 min., 0.2 min., 2.4
      min., 2.3 min. and 10.5 min., respectively. Only buprenorphine and fentanyl
      appeared to be highly lipophilic in the human fat tissue experiments; no
      difference was found between epidural or subcutaneous fat in this respect. The in
      vitro protein binding of oxycodone was 38%, of morphine 31% and of fentanyl 87%
      in average. It is concluded that, in terms of physiochemical properties,
      liposolubility and protein-binding, oxycodone resembles morphine more than it
      does fentanyl.

PMID- 8159634
TI  - Newer neuromuscular blocking agents.
AB  - Four neuromuscular blocking drugs, doxacurium, mivacurium, pipecuronium, and
      rocuronium have been or are about to be introduced into clinical practice. The
      purpose of this MiniReview is to describe their pharmacology, to consider their
      place in clinical anaesthetic practice, and to examine whether the needs of the
      clinician have been met. Two of the agents (doxacurium, mivacurium) are
      benzylisoquinolines resembling atracurium and two (pipecuronium, rocuronium) are
      aminosteroids related to pancuronium and vecuronium. Two (doxacurium,
      pipecuronium) are long-acting compounds, similar in duration of action to
      pancuronium, although the need for such a profile is questionable. Rocuronium has
      an intermediate duration of action and produces its maximum effect within two
      minutes which is much more rapid than any other non-depolarizing relaxant and
      this is probably a result of its poor potency. However, the onset of paralysis is
      not as quick as after succinylcholine. Mivacurium is unique because it is
      metabolized by plasma cholinesterase which produces a rapid recovery although
      slower than succinylcholine. All of the new drugs are devoid of serious
      cardiovascular or other side effects. The anaesthetist is now presented with an
      armamentarium of safe, nondepolarizing muscle relaxants with varying durations of
      action. However, the rapid onset and recovery associated with succinylcholine are
      unique and important in the urgent control of a patient's airway and respiration.
      The indications for succinylcholine will not disappear and the search for a non
      polarizing replacement will continue.

PMID- 8159635
TI  - The involvement of muscarinic receptor subtypes in the mediation of hypothermia,
      tremor, and salivation in male mice.
AB  - The potency of centrally administered non-selective (atropine and N-methyl
      scopolamine) and putatively selective muscarinic antagonists (pirenzepine, AF-DX
      116 and 4-DAMP) in inhibition of oxotremorine-induced hypothermia, tremor and
      salivation in male mice has been compared with their potency in vitro in three
      functional systems, where muscarinic effects are mediated preferentially by M1
      (i.e. superior cervical ganglion), M2 (i.e. atrium), and M3 (i.e. ileum)
      receptors. Atropine, N-methyl scopolamine and 4-DAMP potently abolished the
      effects of oxotremorine. Pirenzepine abolished tremor and salivation, whereas
      hypothermia was antagonized partially only. AF-DX 116 had but weak antagonistic
      effects. Atropine and N-methyl scopolamine were potent antagonists in all three
      in vitro test systems. High potency was also seen with 4-DAMP, in particular in
      the ileum preparation. Pirenzepine showed its highest potency in the ganglion
      preparation. AF-DX 116 was a weak and non-selective antagonist in all three in
      vitro preparations. Our studies indicate that the muscarinic induction of tremor
      and salivation may be preferentially mediated by M3 receptors whereas both M2 and
      M3 receptors may be involved in the mediation of hypothermia. However, the
      overall conclusion is that compounds with higher receptor subtype selectivity are
      needed.

PMID- 8159636
TI  - Comparison of the effects of propofol and thiopental on the pattern of maximal
      electroshock seizures in the rat.
AB  - The anticonvulsant effects of propofol and thiopental (thiopentone) were
      determined by measuring the durations of the various phases of maximal
      electroshock seizures in the rat. Five min. after intraperitoneal administration
      of subanaesthetic (6.25, 12.5 and 25 mg/kg) and 50 mg/kg doses of propofol, the 2
      highest doses abolished both tonic hindlimb extensor phases (full and partial
      extension) in all rats and decreased the duration of the total tonic phases of
      the seizure. Although the lowest dose produced no effect, the 12.5 mg/kg dose
      decreased the duration of both the full and partial tonic extensor phases and
      increased the duration of tonic flexion, showing that even this low dose had
      anticonvulsant activity. Subanesthetic doses of thiopental (5, 10 and 20 mg/kg)
      produced similar changes in the maximal electroshock seizures except that even
      the lowest dose also significantly decreased the duration of total extension and
      total tonus. Postseizure depression was prolonged only by the highest dose of
      propofol. Thus, even low doses of either propofol or thiopental, that produced
      only minimal behavioural effects, had marked anticonvulsant effects against
      electrically induced convulsions in the rat. No evidence of enhanced convulsant
      maximal electroshock seizures patterns was observed at any dose.

PMID- 8159637
TI  - Absorption kinetics of two highly concentrated preparations of growth hormone: 12
      IU/ml compared to 56 IU/ml.
AB  - The purpose of this study was to compare the relative bioavailability of two
      highly concentrated (12 IU/ml versus 56 IU/ml) formulations of biosynthetic human
      growth hormone administered subcutaneously. After pretreatment with growth
      hormone for at least four weeks, nine growth hormone deficient patients with a
      mean age of 26.2 years (range 17-43) were studied two times in a randomized
      design, the two studies being separated by at least one week. At the start of
      each study period (7 p.m.), growth hormone was injected subcutaneously in a
      dosage of 3 IU/m2. The 12 IU/ml preparation of growth hormone was administered on
      one occasion, and the 56 IU/ml preparation on the other. Serum profiles of growth
      hormone were monitored by frequent measurements for 24 hr. Bioavailability and
      absorption dynamics were evaluated by the absorption fraction, F56 IU/12 IU,
      calculated from the mean integrated levels (AUC) of growth hormone, and the
      observed time, Tmax, to reach maximum concentration, Cmax. Levels of serum IGF-I,
      IGFBP-3, insulin and blood glucose were measured to study the short term
      metabolic effects of growth hormone. The absorption fraction, F (S.D.) was 1.034
      (0.163). The 90% confidence interval was 0.934-1.144, which is included in the
      interval 0.8-1.25, implying that the two preparations are bioequivalent. Neither
      AUC (P = 0.90), Cmax (p = 0.47) or Tmax (P = 0.86) for the two formulations of
      growth hormone were significantly different. Similar levels of serum IGF-I, IGFBP
      3, insulin and blood glucose were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159638
TI  - Decreased plasma corticosterone levels in suckling mice following injection of
      the adrenal toxicant, MeSO2-DDE, to the lactating dam.

PMID- 8159639
TI  - Liver stem cells.

PMID- 8159640
TI  - Detection of human papillomaviruses in paraffin-embedded biopsies of cervical
      intraepithelial lesions: analysis by immunohistochemistry, in situ hybridization,
      and the polymerase chain reaction.
AB  - One hundred and forty biopsies with an initial diagnosis of cervical
      intraepithelial lesion (CIL) were tested for the presence of human papillomavirus
      (HPV) by immunohistochemistry and in situ hybridization using commercial
      biotinylated probes (Vira-Type in situ assay; Digene Diagnostics, Silver Spring,
      MD) or probes labeled with digoxigenin by the random primer technique.
      Immunohistochemistry was more inferior to the in situ hybridization method, with
      a detection rate of 14% (20/140) compared to 61% (86/140) for the in situ assay
      with the digoxigenin-labeled probes. Biotinylated probes proved to be slightly
      less sensitive than digoxigenin-labeled probes, with a detection rate of 53%
      (74/140). Although less sensitive in our series taken as a whole,
      immunohistochemistry was positive in a few cases of CILs negative by in situ
      hybridization, so that the association of these techniques gave the highest
      detection rate (66%; 92/140). The CILs that remained negative with these methods
      (34%; 48/140) were investigated by the polymerase chain reaction (PCR) using
      consensus primers to determine definitively the presence of HPV in these lesions
      and were reviewed histologically to assess the diagnosis of CILs. The PCR method
      increased the detection rate of HPV in our series to 76% (107/140). The diagnosis
      of CILs was confirmed for all the biopsy specimens positive by PCR (15/15; 100%)
      and for all the HPV negative tissues with histological features of a high-grade
      lesions (7/7; 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159641
TI  - Improved diagnostic accuracy in needle biopsy interpretation using molecular
      probes.
AB  - A prospective study of computed tomographically guided core needle biopsy samples
      was done to determine whether diagnostic accuracy could be improved in these
      specimens. Eighteen specimens from 16 patients were analyzed by routine and
      immunohistochemical stains on paraffin-embedded tissue and DNA probe
      hybridization on frozen tissue. Pathologic diagnoses based on light microscopy
      and immunostaining were malignant lymphoma (8), lymphoid tissue (1), malignant
      tumor (3), fibrous tissue (2), fatty liver and hepatic adenoma (2), giant cell
      tumor (1), and necrotic tissue (1). Analyzable DNA was obtained from nine
      specimens (50%); 67% of those yielding insufficient DNA (six of nine) were
      samples of benign liver, connective tissue, and necrotic tissue. Extracted DNA
      was hybridized with probes for JH, JK, CT beta, and bc/II. In 67% of analyzable
      cases (six of nine) the diagnosis of lymphoma was confirmed; in 33% the diagnosis
      of lymphoma or nonlymphoma was aided or resolved when the pathologic diagnosis
      was uncertain. Of the eight cases of lymphoma diagnosed by light microscopy, six
      were confirmed by genotyping and two yielded insufficient DNA for analysis. In
      all nine cases with sufficient DNA, hybridization identified B-cell monoclonality
      and confirmed or excluded follicular center cell origin, data not uniformly
      obtained with other studies. Molecular analysis can be a useful adjunct to
      routine methods of diagnosis of needle specimens, improving diagnostic accuracy
      in at least one-third of cases.

PMID- 8159642
TI  - Detection of cytomegalovirus in formalin-fixed paraffin-embedded donor, native
      and allograft liver tissue using a multiplex polymerase chain reaction-liquid
      hybridization assay.
AB  - A multiplex polymerase chain reaction (PCR)-liquid hybridization assay detecting
      a minimum 10 fg of cytomegaloviral (CMV) DNA has been developed. This assay
      successfully detected viral nucleic acids in 25/26 (96.2%) routinely embedded
      allograft liver biopsies with CMV hepatitis. No CMV DNA was detected in 15 native
      and 12 donor liver tissues sampled at the time of liver transplantation. These
      results indicate that archived formalin-fixed, paraffin-embedded liver tissues
      obtained from patients with significant liver disease can be successfully
      analyzed for CMV by PCR, retrospectively. Failure to detect CMV in native and
      donor livers implies that any latent virus present within these tissues is very
      focally distributed, or is below the threshold of detection applicable to PCR.

PMID- 8159644
TI  - Genital papillomaviruses and related neoplasms: causation, diagnosis and
      classification (Bethesda).

PMID- 8159643
TI  - Mucopolysaccharidosis VII: postmortem biochemical and pathological findings in a
      young adult with beta-glucuronidase deficiency.
AB  - The postmortem biochemical and pathological findings in the first patient
      reported with mucopolysaccharidosis VII are described. Clinical, radiographic,
      and biochemical features of this 19-yr-old black man were initially reported in
      1973 when, at age 2 1/2 yr his enzymatic defect, deficiency of beta
      glucuronidase, was identified. The autopsy findings are now described with
      biochemical data further characterizing the enzyme deficiency and resultant
      glycosaminoglycan accumulation. He had dysostosis multiplex and extensive
      cardiovascular lesions including arterial stenosis, and marked fibrous thickening
      of the atrioventricular and aortic valves. Microscopic evidence of lysosomal
      storage was found in bone, cartilage, arteries and cardiac valves, liver, spleen,
      lymph nodes, eyes, adrenal, pituitary, and the central nervous system. In the
      brain, storage was localized to specific regions, primarily intraneuronal, and
      appeared ultrastructurally as delicate whorled filamentous accumulations in
      lysosomes. Similar filamentous storage also occurred in medial cells of the
      aorta. Multiple postmortem tissues contained only trace amounts of beta
      glucuronidase and elevated glycosaminoglycans, predominantly chondroitin 4- and 6
      sulfate.

PMID- 8159645
TI  - Correspondence re: David F. Hardwick, Alan Husted, and James E. Dimmick. Economic
      analysis of the clinical laboratory: labor implications. Mod Pathol 6:220, 1993.

PMID- 8159646
TI  - Correspondence re: Philip T. Cagle, Robert Wessels, and S. Donald Greenberg.
      Concurrent mesothelioma and adenocarcinoma of the lung in a patient with
      asbestosis. Mod Pathol 6:438, 1993.

PMID- 8159647
TI  - Assessment of Ki-67-derived tumor proliferative activity in colorectal
      adenocarcinomas.
AB  - Analysis of tumor growth fraction (TGF) has become essential as cell cycle
      directed modalities have been increasingly used for the treatment of solid
      neoplasms. We studied TGF in fresh tissue samples from 74 surgically resected
      colorectal carcinomas (50 colon and 24 rectum; 44 men and 30 women) by flow
      cytometry (FCM) and by immunostaining using Ki-67 monoclonal antibody. In 12
      cases, samples of uninvolved colonic mucosa adjacent to tumor (transitional
      mucosa) and samples of normal mucosa (at least 5 cm away from tumor) were
      available for growth fraction analysis. The mean Ki-67 and S-phase values were
      17.1% (range, 0-60%) and 17.5% (range, 3-39%), respectively. The mean percentage
      of Ki-67 positivity in tumor samples from women was significantly lower than that
      in samples from men (P = 0.001). Ki-67-derived TGF values, however, did not
      correlate with patient age, lymph node status, or tumor size, site, stage, degree
      of differentiation, or DNA ploidy. The correlation between Ki-67-derived and FCM
      derived TGF values was statistically significant (P = 0.001) but marginal (R =
      0.35). In both transitional and normal colonic mucosa samples, Ki-67 positivity
      was mainly confined to the lower half of the crypts, and their growth fraction
      values were significantly lower than those of tumor tissue; however, there was no
      difference in values between transitional and normal mucosae. Our results
      indicate that Ki-67-derived TGF does not correlate with known prognostic factors
      for colorectal carcinoma; however, long-term follow-up information will be
      necessary to define the clinical value of Ki-67 staining.

PMID- 8159648
TI  - VBEC: very busy endothelial cell.

PMID- 8159649
TI  - Fine-needle aspiration biopsy cytology of myositis ossificans.
AB  - Increased utilization of fine-needle aspiration cytology to better define mass
      lesions before surgical excision can occasionally expose a cytologically
      worrisome yet biologically benign proliferative process. Such a proliferation may
      mimic a malignant neoplasm but is actually benign. Because of its limited
      exposure in the literature, we describe the cytopathology of two cases of
      myositis ossificans obtained by the fine-needle aspiration biopsy technique. Both
      lesions occurred in adolescents. One involved the deep muscle of the thigh,
      whereas the other was a superficial lesion of the anterior abdominal subcutaneous
      fat. In both instances a benign entity was favored, but in one case sarcoma could
      not be absolutely excluded by fine-needle aspiration cytology. Follow-up surgical
      excision in one case, and incisional biopsy in the other confirmed the diagnosis
      of myositis ossificans (MO). The cytologic differential diagnosis of this lesion
      is discussed.

PMID- 8159650
TI  - Liver cell dysplasia in alpha-1-antitrypsin deficiency.
AB  - Large cell liver cell dysplasia (LCD), a suggested preneoplastic change
      progressing to hepatocellular carcinoma, has been reported associated with alpha
      1-antitrypsin deficiency which in some countries has an increased frequency of
      hepatocellular carcinoma. We examined the nonneoplastic liver from 13 alpha-1
      antitrypsin deficiency patients for LCD and, using a labeled streptavidin-biotin
      technique, for immunohistochemical markers: AAT (1/200), hepatitis B surface
      (HBsAg, prediluted) and core (HBcAg, 1/400) antigens, and monoclonal (1/20) and
      polyclonal (1/40) mutant p53, a tumor suppressor gene. There were eight males and
      five females ranging from 2 mo to 76 yr (mean 40 yr). Nine livers showed
      cirrhosis, one chronic persistent hepatitis, one portal fibrosis, and two
      cholestatic hepatitis (in the two infants). The nine cases with LCD included five
      males and four females of mean age 46 yr (range, 17-71), eight with cirrhosis and
      one with portal fibrosis. Only one liver with LCD and cirrhosis had HBcAg in
      cirrhotic and dysplastic cells. No patient had developed hepatocellular
      carcinoma. All 13 livers were immunonegative for HBsAg and mutant p53, and
      immunopositive for AAT present in normal, cirrhotic, and dysplastic liver cells.
      Thus, LCD was identified in 82% of adult alpha-1-antitrypsin deficiency livers
      (69% including infantile patients), 89% with cirrhosis, and none with malignancy.
      HB expression was rarely present; serology for HB and/or hepatitis C was positive
      in 46% adults. Immunoreactive AAT was present in dysplastic cells. p53 gene
      mutations do not appear to have a role in the pathogenesis of LCD in alpha-1
      antitrypsin deficiency.

PMID- 8159652
TI  - Epithelioid stromal cells in lymphocytic mastitis--a source of confusion with
      invasive carcinoma.
AB  - Fourteen examples of lymphocytic mastitis (LM) with epithelioid stromal cells
      characterized by formation of a palpable, hard breast mass composed of a
      predominantly lobulocentric lymphocytic infiltrate, stromal fibrosis, and an
      unusual stromal infiltrate of epithelioid cells are presented. The epithelioid
      cells were so prominent and abundant that the possibility of an infiltrating
      carcinoma was raised in three cases, and a fourth case was misinterpreted as a
      granular cell tumor. Interestingly, eight of the 12 women and the only male
      patient had long standing, insulin dependent diabetes mellitus (IDDM), whereas
      two had IDDM and hypothyroidism, one had hypothyroidism alone, and one had
      systemic lupus erythematosus. Contrary to the conclusions in a recent report, our
      findings indicate that these mammary changes are not exclusive to patients with
      IDDM, and may also occur in nondiabetic patients particularly those with
      autoimmune disorders. The morphologic features of the epithelioid stromal cells
      which have been mistaken for infiltrating carcinoma are emphasized;
      immunohistochemical and ultrastructural findings favoring their myofibroblastic
      nature are presented.

PMID- 8159651
TI  - Ploidy results in prostatic carcinoma vary with sampling method and with
      cytometric technique.
AB  - To evaluate the effect of sampling method and cytometric method on DNA ploidy
      results, a comparison study was performed on 20 whole prostate glands removed at
      prostatectomy. Fresh sampling was by sampling fine-needle aspiration (FNA).
      Paraffin sampling was by microdissection and re-embedding of 3 to 13 (average 6)
      5-mm foci of microscopically proven tumor. Analysis was by flow cytometry and by
      image cytometry (microscopically guided). In tumor negative cases, flow and image
      cytometry of the FNA was diploid in each case, and flow cytometry of paraffin
      embedded tissue was diploid in 5/6 cases. In tumor positive cases, non-diploid
      tumor was detected by image cytometry of the FNA in 70%, by flow cytometry of the
      FNA in 29%, and by flow cytometry of paraffin-extracted nuclei in 21%. The most
      effective combination was sampling fine-needle aspiration and image analysis.

PMID- 8159653
TI  - Evaluation of T-lymphocytes in esophageal mucosal biopsies.
AB  - We previously demonstrated that in esophageal mucosal biopsies, intraepithelial
      cells with irregular nuclear contours (CINC) as well as mononuclear cells with
      round nuclei are T-lymphocytes and we suggested that they may be an independent
      marker of esophagitis. To investigate this hypothesis, we evaluated Hematoxylin
      and eosin-stained biopsy specimens from 201 consecutive patients (115 female, 86
      male; mean age: 52 years) that showed either no accepted features of esophagitis
      (n = 122) or changes typical of esophageal reflux (n = 79). The number of
      intraepithelial CINC and mononuclear cells in the most densely populated high
      power field were counted. Twenty-two of these biopsies were also stained with
      UCHL-1 (T-lymphocyte marker) and L-26 (B-lymphocyte marker). All medical records
      were reviewed to determine clinical and endoscopic findings of esophagitis, which
      were then compared with the histologic results for correlations. The
      immunohistochemical results confirmed that the majority (> 95%) of CINC and
      mononuclear cells were T-lymphocytes, and the sum of CINC and mononuclear cells
      represents best the number of T-lymphocytes. The number of T-lymphocytes was
      significantly correlated with that of eosinophils (R = 0.24, P = 0.0008) but not
      with neutrophils (R = 0.069, P = 0.33). They were greater in number, although not
      significantly so, in the specimens with histologic evidence of esophagitis than
      those without (12.7 +/- 8.9 versus 11.3 +/- 7.7, P = 0.23).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8159654
TI  - Mediastinal lymphoblastic lymphoma with non-lymphoblastic histologic features.
AB  - The clinical and pathologic features of an unusual case of mediastinal lymphoma
      in a 46-yr-old man are presented. Histology of the tumor was that of a diffuse,
      non-large cell lymphoma. The nuclear chromatin was coarse, suggesting a
      relatively mature stage of lymphocyte maturation, and the lymphoma was
      provisionally classified as diffuse small-cleaved cell lymphoma. Immunohistologic
      study and cell surface marker analysis revealed a common thymocytic phenotype
      (CD3, CD1a, CD4, CD8, and TdT positive), however, and DNA flow cytometric
      analysis revealed a high S+G2 M fraction of 29%. With the immunostaining profile
      accepted as definitive for lymphoblastic lymphoma, histologic features were
      reassessed in retrospect. Cells having nuclear features typical of lymphoblasts
      were not recognized. Occasional cases of lymphoblastic lymphoma may not be
      recognizable when evaluated only by histology using the generally accepted
      criteria for diagnosis.

PMID- 8159655
TI  - Therapy associated differentiation in rhabdomyosarcomas.
AB  - The morphologic and immunophenotypical features of three embryonal and one
      spindle cell rhabdomyosarcomas that underwent marked cytologic differentiation
      after polychemotherapy are described. In all the cases the morphologic changes
      were associated to disappearance of vimentin immunoreactivity and intense
      positivity for desmin, muscle specific actins, and myoglobin; in addition the
      differentiated tumor cells acquired a strong and continuous pericellular staining
      for laminin. The mitotic activity was significantly decreased. Drug associated
      differentiation seems to recapitulate the normal myogenic development to the
      point that the more mature neoplastic cells may represent terminally
      differentiated elements withdrawn from cell cycle. However, due to the
      persistence of a small number of poorly differentiated rhabdomyoblasts, the
      clinical consequences of this phenomenon are unclear.

PMID- 8159656
TI  - Clinicopathologic significance of cathepsin B immunostaining in transitional
      neoplasia.
AB  - Fifty Stage heterogeneous urinary bladder carcinomas were immunostained for
      cathepsin B, a lysosomal endoproteinase putatively associated with tumor
      invasion. Neoplastic cell CB immunoreactivity was strongly correlated to both
      grade (I/II--42% positive versus III--68% positive, P = 0.01) and invasion beyond
      the lamina propria (Ta/T1--42% positive versus T2/T3--68% positive, P = 0.02).
      Most low grade, papillary tumors displayed a granular cytoplasmic staining
      pattern, compatible with lysosomal distribution, in contrast to high grade
      tumors, in which diffuse staining was present in the cytoplasm. Staining was also
      accentuated at the advancing front of invading tumors and in angiolymphatic tumor
      emboli. Non-neoplastic mononuclear inflammatory cells, particularly those at the
      host-tumor interface, displayed variable, sometimes intense staining. Strong
      tumor-cell CB was more frequent among recurrent TCC than in patients who remain
      free of disease (55% versus 29%, n = 18, T2-3, cystectomy, 5-yr min. follow-up).
      We conclude these observed staining patterns and grade/stage associations are
      compatible with an important biological role for CB in facilitating host invasion
      in some bladder tumors. Levels and/or distribution of CB may also be of potential
      value in defining clinically aggressive tumor subsets.

PMID- 8159657
TI  - Mesothelial/monocytic incidental cardiac excrescences: cardiac MICE.
AB  - We have identified four new cases of the cardiac lesion resembling a histiocytoid
      (epithelioid) hemangioma from the consultation and surgical pathology files of
      the Mayo Clinic from 1979 to 1992. The lesions occurred in two men and two women,
      mean age 60 yr (range, 55 to 63), three of whom had undergone previous cardiac
      catheterization. All were found incidentally, two as separate tissue fragments
      obtained by right ventricular endomyocardial biopsy during investigations for
      dilated cardiomyopathy, and two during mitral valve replacement (one free
      floating in the left atrium and the other attached to the mitral valve). The
      latter two lesions measured 1.0 and 0.8 cm. All were composed of histiocytes
      (macrophages) focally admixed with cuboidal cells which formed strips and tubular
      arrays in three cases. Immunohistochemistry (two cases) confirmed their biphasic
      nature with cytokeratin positivity of the cuboidal cells and CD68 (KP-1)
      positivity (macrophage-myeloid lineage) of the histiocytes. Carcinoembryonic
      antigen and Leu-M1 were negative for both cell types. Transmission electron
      microscopy (two cases) showed macrophage-like cells and cuboidal cells with
      intracytoplasmic intermediate filaments, desmosome-like cellular junctions, and
      rough endoplasmic reticulum consistent with mesothelial cells. All four patients
      had a benign clinical course (range, 2 mo to 13 yr). This mesothelial and
      monocytic (histiocytic) process is postulated to relate to previous cardiac
      catheterization (applicable in three of our patients). The importance of these
      nodules, which are likely reactive, is their potential confusion with metastatic
      adenocarcinoma. We propose the name mesothelial/monocytic incidental cardiac
      excresences (cardiac MICE) for these lesions.

PMID- 8159659
TI  - Plasminogen activators and inhibitors in gliomas: an immunohistochemical study.
AB  - The tissue (tPA) and urokinase (uPA) types of plasminogen activator and the
      plasminogen activator inhibitor 1 (PAI-1) are enzymatic proteins that may play an
      important role in the degradation of the extracellular matrix in physiologic and
      neoplastic conditions. In particular, urokinase may underlie key properties of
      malignant cells, such as invasiveness and dissemination. We have studied the
      immunohistochemical distribution of tPA, uPA, and PAI-1 in 24 human gliomas,
      including seven well-differentiated astrocytomas, three oligodendrogliomas, six
      anaplastic astrocytomas, and eight glioblastomas multiforme. All anaplastic
      astrocytomas and glioblastomas showed numerous neoplastic cells immunoreactive
      for uPA, but not for tPA. In contrast, low-grade gliomas were negative for uPA,
      but contained some tPA-immunoreactive cells. Endothelial cells of vessels in non
      neoplastic and neoplastic brain were immunoreactive for tPA, but not for uPA or
      PAI-1. Non-neoplastic glia were unreactive for tPA, uPA, and PAI-1. Small
      anaplastic cells present in three glioblastomas showed immunoreactivity for PAI
      1. The presence of a large number of uPA-immunoreactive neoplastic cells in high
      grade gliomas suggest that this fibrinolytic protein plays a significant role in
      the invasive properties of these neoplasms.

PMID- 8159658
TI  - Richter's transformation of chronic lymphocytic leukemia with Hodgkin's-like
      cells is associated with Epstein-Barr virus infection.
AB  - The appearance of a high-grade lymphoma in the setting of B-cell chronic
      lymphocytic leukemia (CLL) is termed Richter's syndrome. Usually the high-grade
      component is a monomorphous, large cell lymphoma, but occasionally the high-grade
      component takes the form of Hodgkin's disease or a Hodgkin's-like lymphoma.
      Although Richter's syndrome is thought to represent clonal evolution of the
      underlying B-cell neoplasm in most cases, such a progression is difficult to
      explain when the high-grade component is Hodgkin's disease. We report two cases
      of Richter's syndrome in which the large cells had a morphology consistent with
      Reed-Sternberg cells and were found in a background of CLL. The large cells in
      both cases expressed the CD15 and CD30 antigens in a pattern characteristic of
      Reed-Sternberg cells, and the large cells in one case also expressed monotypic
      cytoplasmic immunoglobulin of the same type as that expressed by the underlying
      CLL. In both cases, Southern blot analysis of DNA from lymph nodes that contained
      both CLL and the Hodgkin's-like component showed single immunoglobulin gene
      rearrangements. Using the polymerase chain reaction, we found Epstein-Barr virus
      DNA in lymph nodes from both cases, and in peripheral blood lymphoid cells from
      one case 4 yr before the onset of Richter's syndrome. Immunoperoxidase staining
      showed expression of EBV latent membrane protein only in the Reed-Sternberg-like
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159660
TI  - Protein crystallography for all.

PMID- 8159661
TI  - Crystallization and structural analysis of bullfrog red cell L-subunit ferritins.
AB  - Ferritin is a 24 subunit protein that controls biomineralization of iron in
      animals, bacteria, and plants. Rates of mineralization vary among members of the
      ferritin family, particularly between L and H type subunits of animal ferritins
      which are differentially expressed in various cell types. To examine ferritin
      from a highly differentiated cell type and to clarify the relationship between
      ferritin structure and function, bullfrog red cell L ferritin has been cloned,
      overexpressed in E. coli, and crystallized under two conditions. Crystals were
      obtained at high ionic strength in the presence of MnCl2 at a concentration
      comparable to that of the protein and in the presence of MgCl2 at a concentration
      much higher than that of the protein. Under both crystallization conditions, the
      crystals are tetragonal bipyramids in the space group F432 with unit cell
      dimensions a = b = c = 182 +/- 0.5 A. Crystals obtained in the presence of
      manganese and ammonium sulfate diffract to 1.9 A, while those obtained in the
      presence of magnesium and sodium tartrate diffract to 1.6 A. Isomorphous crystals
      have been obtained under similar conditions for a site-directed mutant with a
      reduced mineralization rate in which Glu-57, -58, -59, and -61 are all replaced
      by Ala. The structure of wild type L-subunit with magnesium has been solved by
      molecular replacement using the calcium salt of human liver H subunit (Lawson et
      al., Nature (London) 349:541-544, 1991) as the model. The crystallographic R
      factor for the 6-2.2 A shell is 0.21. The overall fold of human H and bullfrog L
      ferritins is similar with an rms difference in backbone atomic positions of 0.97
      A. The largest structural differences occur in the D helix and the loop
      connecting the D and E helices of the four helix bundle. Because red cell L
      ferritin and liver H ferritin show differences in both rates of mineralization
      and three-dimensional structure, more detailed comparisons of these structures
      are likely to shed new light on the relationship between conformation and
      function.

PMID- 8159662
TI  - Evaluation of the conformational free energies of loops in proteins.
AB  - In this paper we discuss the problem of including solvation free energies in
      evaluating the relative stabilities of loops in proteins. A conformational search
      based on a gas-phase potential function is used to generate a large number of
      trial conformations. As has been found previously, the energy minimization step
      in this process tends to pack charged and polar side chains against the protein
      surface, resulting in conformations which are unstable in the aqueous phase.
      Various solvation models can easily identify such structures. In order to provide
      a more severe test of solvation models, gas-phase conformations were generated in
      which side chains were kept extended so as to maximize their interaction with the
      solvent. The free energies of these conformations were compared to that
      calculated for the crystal structure in three loops of the protein E. coli RNase
      H, with lengths of 7, 8, and 9 residues. Free energies were evaluated with a
      finite difference Poisson-Boltzmann (FDPB) calculation for electrostatics and a
      surface area-based term for nonpolar contributions. These were added to a gas
      phase potential function. A free energy function based on atomic solvation
      parameters was also tested. Both functions were quite successful in selecting,
      based on a free energy criterion, conformations quite close to the crystal
      structure for two of the three loops. For one loop, which is involved in crystal
      contacts, conformations that are quite different from the crystal structure were
      also selected. A method to avoid precision problems associated with using the
      FDPB method to evaluate conformational free energies in proteins is described.

PMID- 8159663
TI  - A connected-cluster of hydration around myoglobin: correlation between molecular
      dynamics simulations and experiment.
AB  - An analysis of a molecular dynamics simulation of metmyoglobin in an explicit
      solvent environment of 3,128 water molecules has been performed. Both statics and
      dynamics of the protein-solvent interface are addressed in a comparison with
      experiment. Three-dimensional density distributions, temperature factors, and
      occupancy weights are computed for the solvent by using the trajectory
      coordinates. Analysis of the hydration leads to the localization of more than 500
      hydration sites distributed into multiple layers of solvation located between 2.6
      and 6.8 A from the atomic protein surface. After locating the local solvent
      density maxima or hydration sites we conclude that water molecules of hydration
      positions and hydration sites are distinct concepts. Both global and detailed
      properties of the hydration cluster around myoglobin are compared with recent
      neutron and X-ray data on myoglobin. Questions arising from differences between X
      ray and neutron data concerning the locations of the protein-bound water are
      investigated. Analysis of water site differences found from X-ray and neutron
      experiments compared with our simulation shows that the simulation gives a way to
      unify the hydration picture given by the two experiments.

PMID- 8159664
TI  - Distribution function implied dynamics versus residence times and correlations:
      solvation shells of myoglobin.
AB  - The dynamics of water at the protein-solvent interface is investigated through
      the analysis of a molecular dynamics simulation of metmyoglobin in explicit
      aqueous environment. Distribution implied dynamics, harmonic and quasi-harmonic,
      are compared with the simulated macroscopic dynamics. The distinction between
      distinguishable solvent molecules and hydration sites developed in the previous
      paper is used. The simulated hydration region within 7 A from the protein surface
      is analyzed using a set of 551 hydration sites characterized by occupancy weights
      and temperature B-factors determined from the simulation trajectory. The
      precision of the isotropic harmonic and anisotropic harmonic models for the
      description of proximal solvent fluctuations is examined. Residence times and
      dipole reorientation times of water around the protein surface are compared with
      NMR and ESR results. A correlation between diffraction experiment quantities such
      as the occupancy weights and temperature factors and the residence and
      correlation times resulting from magnetic resonance experiments is found via
      comparison with simulation.

PMID- 8159665
TI  - The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and
      NADPH reduced state.
AB  - The three-dimensional structure of trypanothione reductase (TR) (EC 1.6.4.8) from
      Trypanosoma cruzi has been solved at 0.33 nm resolution by molecular replacement
      using the structure of C. fasciculata TR as a starting model. Elucidation of the
      T. cruzi TR structure represents the first step in the rational design of a drug
      against Chagas' disease. The structure of T. cruzi TR is compared with those of
      C. fasciculata TR as well as human and E. coli glutathione reductase (GR). In the
      FAD-binding domain, TR has two insertions, each about 10 residues long, which do
      not occur in GR. The first one is a rigid loop stabilizing the position of helix
      91-117 which is responsible for the wider active site of TR as compared to GR.
      The second insertion does not occur where it is predicted by sequence alignment;
      rather the residues extend three strands of the 4-stranded beta-sheet by one or
      two residues each. This increases the number of hydrogen bonds within the sheet
      structure. The structure of the NADPH.TR complex has been solved at 0.33 nm
      resolution. The nicotinamide ring is sandwiched between the flavin ring and the
      side chain of Phe-198 which undergoes the same conformational change upon
      coenzyme binding as Tyr-197 in GR. In addition to Arg-222 and Arg-228, which are
      conserved in TR and GR, Tyr-221--the last residue of the second beta-sheet strand
      of the beta alpha beta dinucleotide binding fold--is in hydrogen bonding distance
      to the 2' phosphate group of NADPH.

PMID- 8159666
TI  - A molecular dynamics approach for the generation of complete protein structures
      from limited coordinate data.
AB  - Generation of full protein coordinates from limited information, e.g., the C
      alpha coordinates, is an important step in protein homology modeling and
      structure determination, and molecular dynamics (MD) simulations may prove to be
      important in this task. We describe a new method, in which the protein backbone
      is built quickly in a rather crude way and then refined by minimization
      techniques. Subsequently, the side chains are positioned using extensive MD
      calculations. The method is tested on two proteins, and results compared to
      proteins constructed using two other MD-based methods. In the first method, we
      supplemented an existing backbone building method with a new procedure to add
      side chains. The second one largely consists of available methodology. The
      constructed proteins are compared to the corresponding X-ray structures, which
      became available during this study, and they are in good agreement (backbone RMS
      values of 0.5-0.7 A, and all-atom RMS values of 1.5-1.9 A). This comparative
      study indicates that extensive MD simulations are able, to some extent, to
      generate details of the native protein structure, and may contribute to the
      development of a standardized methodology to predict reliably (parts of) protein
      structures when only partial coordinate data are available.

PMID- 8159667
TI  - The enzymatic mechanism of carboxypeptidase: a molecular dynamics study.
AB  - An MD simulation of the system carboxypeptidase A (CPA) with the tetrapeptide Val
      Leu-Phe-Phe has been performed in order to learn about the substrate disposition
      just prior to nucleophilic attack. We have explored the model in which the
      substrate does not substitute the zinc-coordinated water (the "water" mechanism).
      The simulations do suggest as feasible that the Zn-OH2 group performs a
      nucleophilic attack on the Phe-Phe peptidic bond. We have also investigated the
      model in which the carbonyl oxygen displaces the zinc-coordinated water. In this
      case the substrate and Glu-270 orient themselves to allow an anhydride
      intermediate during the peptidic bond cleavage (the "anhydride" mechanism). Based
      on the results of the simulations, both "water" and "anhydride" mechanisms are
      structurally feasible, although the former model seems more probable on chemical
      grounds.

PMID- 8159668
TI  - Crystallization and preliminary structural studies of a chorismate mutase
      catalytic antibody complexed with a transition state analog.
AB  - The Fab' fragment of a catalytic antibody with chorismate mutase activity has
      been crystallized as a complex with the transition-state analog hapten. The
      complex was crystallized by the vapor diffusion method using ammonium sulfate as
      the precipitant. The crystals belong to the orthorhombic space group
      P2(1)2(1)2(1) with unit cell dimensions a = 37.1 A, b = 63.3 A, c = 178.5 A, and
      there is one Fab' molecule per asymmetric unit. The crystals diffract X-rays to
      at least 3.0 A and are suitable for X-ray crystallographic studies.

PMID- 8159669
TI  - Crystallization and preliminary X-ray diffraction studies of a monoclonal
      antibody Fab fragment against foot-and-mouth disease virus and of its complex
      with the main antigenic site peptide.
AB  - The Fab fragment of the neutralizing monoclonal antibody SD6 elicited against
      foot-and-mouth disease virus (FMDV) C-S8c1 and its complex with a peptide,
      corresponding to the major antigenic site of FMDV (VP1 residues 136-150,
      YTASARGDLAHLTTT), have been crystallized using the hanging drop vapor diffusion
      techniques. For the isolated Fab, crystals diffracting to 2.5 A resolution were
      obtained at room temperature using ammonium sulfate as precipitant. These
      crystals are monoclinic, space group C2, and unit cell parameters a = 109.53 A, b
      = 89.12 A, c = 64.04 A, and beta = 112.9 degrees and contain one Fab molecule per
      asymmetric unit. Crystals from the complex diffract, at least, to 2.8 A
      resolution and were obtained, at room temperature, using PEG as precipitant.
      These crystals are monoclinic, space group P2, and unit cell parameters a = 56.11
      A, b = 60.67 A, c = 143.45 A, and beta = 95.4 degrees. Density packing
      considerations indicate that there are two Fab molecules in the asymmetric unit.

PMID- 8159670
TI  - The role of T lymphocytes in inflammation.

PMID- 8159671
TI  - Was the nucleus the first endosymbiont?

PMID- 8159672
TI  - Activation of telomerase in a human tumor.

PMID- 8159673
TI  - Dissecting a complex process.

PMID- 8159674
TI  - B lymphopoiesis: global factors, local control.

PMID- 8159675
TI  - Cloning of Giardia lamblia heat shock protein HSP70 homologs: implications
      regarding origin of eukaryotic cells and of endoplasmic reticulum.
AB  - The genes for two different 70-kDa heat shock protein (HSP70) homologs have been
      cloned and sequenced from the protozoan Giardia lamblia. On the basis of their
      sequence features, one of these genes corresponds to the cytoplasmic form of
      HSP70. The second gene, on the basis of its characteristic N-terminal hydrophobic
      signal sequence and C-terminal endoplasmic reticulum (ER) retention sequence (Lys
      Asp-Glu-Leu), is the equivalent of ER-resident GRP78 or the Bip family of
      proteins. Phylogenetic trees based on HSP70 sequences show that G. lamblia
      homologs show the deepest divergence among eukaryotic species. The identification
      of a GRP78 or Bip homolog in G. lamblia strongly suggests the existence of ER in
      this ancient eukaryote. Detailed phylogenetic analyses of HSP70 sequences by boot
      strap neighbor-joining and maximum-parsimony methods show that the cytoplasmic
      and ER homologs form distinct subfamilies that evolved from a common eukaryotic
      ancestor by gene duplication that occurred very early in the evolution of
      eukaryotic cells. It is postulated that because of the essential "molecular
      chaperone" function of these proteins in translocation of other proteins across
      membranes, duplication of their genes accompanied the evolution of ER or nucleus
      in the eukaryotic cell ancestor. The presence in all eukaryotic cytoplasmic HSP70
      homologs (including the cognate, heat-induced, and ER forms) of a number of
      autapomorphic sequence signatures that are not present in any prokaryotic or
      organellar homologs provides strong evidence regarding the monophyletic nature of
      eukaryotic lineage. Further, all eukaryotic HSP70 homologs share in common with
      the Gram-negative group of eubacteria a number of sequence features that are not
      present in any archaebacterium or Gram-positive bacterium, indicating their
      evolution from this group of organisms. Some implications of these findings
      regarding the evolution of eukaryotic cells and ER are discussed.

PMID- 8159676
TI  - Telomerase activity in human ovarian carcinoma.
AB  - Telomeres fulfill the dual function of protecting eukaryotic chromosomes from
      illegitimate recombination and degradation and may aid in chromosome attachment
      to the nuclear membrane. We have previously shown that telomerase, the enzyme
      which synthesizes telomeric DNA, is not detected in normal somatic cells and that
      telomeres shorten with replicative age. In cells immortalized in vitro,
      activation of telomerase apparently stabilizes telomere length, preventing a
      critical destabilization of chromosomes, and cell proliferation continues even
      when telomeres are short. In vivo, telomeres of most tumors are shorter than
      telomeres of control tissues, suggesting an analogous role for the enzyme. To
      assess the relevance of telomerase and telomere stability in the development and
      progression of tumors, we have measured enzyme activity and telomere length in
      metastatic cells of epithelial ovarian carcinoma. We report that extremely short
      telomeres are maintained in these cells and that tumor cells, but not isogenic
      nonmalignant cells, express telomerase. Our findings suggest that progression of
      malignancy is ultimately dependent upon activation of telomerase and that
      telomerase inhibitors may be effective antitumor drugs.

PMID- 8159677
TI  - Five SWI/SNF gene products are components of a large multisubunit complex
      required for transcriptional enhancement.
AB  - The Saccharomyces cerevisiae SWI1, SWI2 (SNF2), SWI3, SNF5, and SNF6 gene
      products play a crucial role in the regulation of transcription. We provide here
      direct biochemical evidence that all five SWI/SNF polypeptides are components of
      a large multisubunit complex. These five polypeptides coelute from a gel
      filtration column with an apparent molecular mass of approximately 2 MDa. The
      five SWI/SNF polypeptides do not copurify when extracts are prepared from swi- or
      snf- mutants. We show that SWI/SNF polypeptides also remain associated during an
      affinity-chromatography step followed by gel filtration. Assembly of the SWI/SNF
      complex is not disrupted by a mutation in the putative APT-binding site of SWI2,
      although this mutation eliminates SWI2 function.

PMID- 8159678
TI  - Site-specific incorporation of biophysical probes into proteins.
AB  - Biophysical probes which can detect structural changes in proteins and the
      interaction of proteins with other macromolecules are important tools in studying
      protein function. Many difficulties remain, however, in introducing probes into
      proteins site-specifically. Here we report the successful site-specific
      incorporation of a spin-labeled, a fluorescent, and a photoactivatible amino acid
      into a variety of surface and internal sites in bacteriophage T4 lysozyme by
      using unnatural amino acid mutagenesis. In addition, we report the purification
      and spectral characterization of T4 lysozyme mutants containing the spin-labeled
      amino acid and the fluorescent amino acid. The ability to incorporate these
      probes site-specifically allows for novel studies of protein structure and
      dynamics. Moreover, this work demonstrates that the Escherichia coli protein
      biosynthetic machinery can tolerate unnatural amino acids with little resemblance
      to the natural amino acids.

PMID- 8159680
TI  - Role of glutamine-117 in the ribonucleolytic activity of human angiogenin.
AB  - The crystal structure of human angiogenin (reported in the preceding paper in
      this issue) reveals that the site that corresponds to the pyrimidine binding site
      of RNase A is obstructed by Gln-117. Mutation of this residue to Ala and Gly is
      here found to increase activity 11- to 18-fold and 21- to 30-fold, respectively,
      toward dinucleotide, polynucleotide, and cyclic nucleotide substrates, but
      without changing specificity. The enhanced activity of Q117G toward CpA is due to
      a 5-fold decrease in Km and a 6-fold increase in kcat. Its Ki value for 2'-CMP is
      5-fold lower than that of native angiogenin, whereas its Ki value for 5'-AMP is
      unchanged. It has been reported previously that mutating Asp-116 to Ala increases
      activity 15-fold. The double mutant D116A/Q117A is shown to be only slightly more
      active than each individual mutant. The present results demonstrate that Gln-117
      impedes the ribonucleolytic activity of angiogenin, as predicted by x-ray
      crystallography. Moreover, they suggest that prior to or during catalysis
      angiogenin must undergo a conformational change to reorient the C-terminal
      segment that contains this residue, and that a similar reorganization is required
      for the mutants as well. This view is supported by molecular modeling of an
      angiogenin-uridine vanadate complex. These in vitro findings have implications
      for the angiogenic activity of angiogenin in vivo.

PMID- 8159679
TI  - Crystal structure of human angiogenin reveals the structural basis for its
      functional divergence from ribonuclease.
AB  - Angiogenin, a potent inducer of neovascularization, is the only angiogenic
      molecule known to exhibit ribonucleolytic activity. Its overall structure, as
      determined at 2.4 A, is similar to that of pancreatic ribonuclease A, but it
      differs markedly in several distinct areas, particularly the ribonucleolytic
      active center and the putative receptor binding site, both of which are
      critically involved in biological function. Most strikingly, the site that is
      spatially analogous to that for pyrimidine binding in ribonuclease A differs
      significantly in conformation and is "obstructed" by glutamine-117. Movement of
      this and adjacent residues may be required for substrate binding to angiogenin
      and, hence, constitute a key part of its mechanism of action.

PMID- 8159681
TI  - Constraints of thermal noise on the effects of weak 60-Hz magnetic fields acting
      on biological magnetite.
AB  - Previous calculations of limits imposed by thermal noise on the effects of weak
      60-Hz magnetic fields on biological magnetite are generalized and extended to
      consider multiple signals, the possibility of anomalously large magnetosome
      structures, and the possibility of anomalously small cytoplasm viscosities. The
      results indicate that the energies transmitted to the magnetite elements by
      fields less than 5 microT, characteristic of the electric power distribution
      system, will be much less than thermal noise energies. Hence, the effects of such
      weak fields will be masked by that noise and cannot be expected to affect biology
      or, therefore, the health of populations.

PMID- 8159682
TI  - Hydrodynamic steering effects in protein association.
AB  - Protein-ligand reaction rates are often limited by the rate of diffusional
      encounter of the protein and ligand in solution. Reaction rates, however, can be
      much greater than expected, given the necessity for correct orientation before
      reaction. A number of forces can affect the orientation of the protein and ligand
      in solution, and thus increase the reaction rate. We have considered hydrodynamic
      forces, produced when water molecules between protein and ligand must be pushed
      out of the way to allow their encounter. We have used the cleft enzymes as a
      model system, as they could be expected to show strong hydrodynamic effects. One
      particular type of hydrodynamic interaction stands out: a steering torque which
      occurs when the enzyme and substrate move toward each other in solution. The
      magnitude of this steering torque is compared to the mutual torque experienced by
      interacting "protein-sized" dipoles in solution. A simple model is used to
      demonstrate that the hydrodynamic steering torque can be 2 orders of magnitude
      greater than the electrostatic torque.

PMID- 8159683
TI  - Enterochromaffin cells of the digestive system: cellular source of guanylin, a
      guanylate cyclase-activating peptide.
AB  - Guanylin, a bioactive peptide, has recently been isolated from the intestine;
      this peptide activates intestinal guanylate cyclase (i.e., guanylate cyclase C)
      and thus is potentially involved in the regulation of water/electrolyte transport
      in the gastrointestinal mucosa. As yet, the cells involved in synthesis, storage,
      or secretion of guanylin have not been identified by immunocytochemistry. We
      raised antisera against guanylin and investigated the entire gastrointestinal
      tract of guinea pigs by light and electron microscopical immunocytochemistry.
      Extracts of various intestinal segments and plasma analyzed on a Western blot
      revealed a peptide band corresponding to the molecular mass of guanylin.
      Localization studies in the entire digestive tract showed that guanylin is
      exclusively confined to enterochromaffin (EC) cells. Remarkably, most EC cells
      contacted the gut lumen by cell processes that were highly immunoreactive for
      guanylin. In addition to the well known secretion in an endocrine fashion, EC
      cells by circumstantial evidence may release guanylin into the gut lumen to
      activate guanylate cyclase C that is immediately located on the brush border of
      adjacent enterocytes. The unique localization of guanylin in EC cells may
      indicate that these cells are involved in the regulation of fluid secretion in
      the gastrointestinal mucous membrane.

PMID- 8159684
TI  - Mechanosensitive Ca2+ transients in endothelial cells from human umbilical vein.
AB  - We have investigated the changes in intracellular calcium concentration ([Ca2+]i)
      in human endothelial cells induced by mechanical stretch due to osmotic cell
      swelling. Hypotonic solutions also activate a Cl- conductance that has been
      described elsewhere and mainly serves to clamp the membrane potential at negative
      values to provide a driving force for Ca2+ influx. The increase in [Ca2+]i caused
      by hypotonic solutions is due to release from inositol-1,4,5-trisphosphate
      sensitive Ca2+ pools and a subsequent Ca2+ influx, apparently activated by store
      depletion. These changes in [Ca2+]i are completely abolished if the phospholipase
      A2 (PLA2) activity is inhibited by either 4-bromophenacyl bromide or cyclosporin
      A. Arachidonic acid, applied either extracellularly or intracellularly via the
      patch pipette, mimics the mechanosensitive response even in cells with blocked
      PLA2. Metabolites of the lipo- and cyclooxygenase pathways can be excluded.
      Phospholipase C activation and the protein kinase A pathway are not involved in
      this mechanical response. Although no specific pharmacological tools for probing
      the role of PLA2 are available, our evidence suggests that mechanosensitivity in
      endothelial cells may be modulated by arachidonic acid.

PMID- 8159685
TI  - Cyclin D1 expression is regulated by the retinoblastoma protein.
AB  - The product of the retinoblastoma susceptibility gene, pRb, acts as a tumor
      suppressor and loss of its function is involved in the development of various
      types of cancer. DNA tumor viruses are supposed to disturb the normal regulation
      of the cell cycle by inactivating pRb. However, a direct function of pRb in
      regulation of the cell cycle has hitherto not been shown. We demonstrate here
      that the cell cycle-dependent expression of one of the G1-phase cyclins, cyclin
      D1, is dependent on the presence of a functional Rb protein. Rb-deficient tumor
      cell lines as well as cells expressing viral oncoproteins (large tumor antigen of
      simian virus 40, early region 1A of adenovirus, early region 7 of papillomavirus)
      have low or barely detectable levels of cyclin D1. Expression of cyclin D1, but
      not of cyclins A and E, is induced by transfection of the Rb gene into Rb
      deficient tumor cells. Cotransfection of a reporter gene under the control of the
      D1 promoter, together with the Rb gene, into Rb-deficient cell lines demonstrates
      stimulation of the D1 promoter by Rb, which parallels the stimulation of
      endogenous cyclin D1 gene expression. Our finding that pRb stimulates expression
      of a key component of cell cycle control, cyclin D1, suggests the existence of a
      regulatory loop between pRb and cyclin D1 and extends existing models of tumor
      suppressor function.

PMID- 8159686
TI  - Invasion and maintenance of a gene duplication.
AB  - The ubiquity of multigene families is evidence for the frequent occurrence of
      gene duplication, but the origin of multigene families from a single gene remains
      a little-studied aspect of genome evolution. Although it is clear that a
      duplication can arise and become fixed in a population purely by random genetic
      drift and that the rate of fixation is accelerated if the duplication is directly
      advantageous, the nature of gene duplication suggests that other factors may
      influence the fate of a novel duplication. In the face of disadvantageous loss-of
      function mutations, duplication of a functional gene may provide a buffer against
      such mutations. Here the conditions for invasion of a rare duplication starting
      from a mutation-selection balance are derived with formal population genetic
      models in both haploids and diploids. Recurrent duplication protects the
      duplicated chromosome from loss and can be very effective in increasing its
      frequency in a population. In the absence of recurrent duplication, one might
      suppose that a duplication would be favored by natural selection because it can
      mask the effects of deleterious mutations. However, the models show that a
      duplication can invade only if it provides a direct advantage to the organism.
      This result is closely related to recent theoretical work on the evolution of
      ploidy.

PMID- 8159687
TI  - Nervous control of juvenile hormone biosynthesis in Locusta migratoria.
AB  - In Locusta migratoria migratorioides R. and F., two types of brain neurons
      innervate the juvenile hormone (JH)-producing corpora allata (CA). Thirteen cells
      in each pars lateralis (PL) innervate the ipsilateral CA, while four cells (two
      in each PL) innervate both glands. We investigated possible influences of these
      two neuronal types on JH production by a newly developed method. A radiochemical
      assay was used to measure hourly JH production by a CA with intact nerve
      connections to the brain. Then, changes in hormone production due to selective
      nerve stimulation or transection were assessed. In control preparations JH
      production per h remained approximately constant for at least 9 h. Simultaneous
      electrical stimulation of all neurons innervating one CA (i.e., 13 ipsilateral
      plus 4 bilaterally innervating cells) always inhibited JH production, while their
      transection led to a rapid progressive increase in JH biosynthesis in CA from
      females with oocytes longer than 4.5 mm. Thus, there is strong neurally mediated
      inhibition of the CA at certain phases of the vitellogenic cycle. The dramatic
      effects of nerve transection show that in vitro rates of JH production are an
      unreliable indicator of in vivo levels. Selective stimulation of the four neurons
      innervating both CA suggests that they do modulate JH biosynthesis but the effect
      varies qualitatively depending on the phase of the vitellogenic cycle.

PMID- 8159688
TI  - Ankyrin binds to two distinct cytoplasmic domains of Na,K-ATPase alpha subunit.
AB  - Ankyrin has emerged as a ubiquitous protein linking integral membrane transport
      proteins such as Na,K-ATPase to an underlying spectrin cytoskeleton. This
      interaction is mediated by the alpha subunit of Na,K-ATPase; however, the nature
      of the ankyrin binding site in Na,K-ATPase is unknown. As a step to determine the
      mechanism of this interaction, the ankyrin binding region of human erythrocyte
      spectrin and each of five putative cytoplasmic domains of the Na,K-ATPase alpha
      subunit have been prepared as recombinant fusion proteins in bacteria and
      analyzed for their interaction with erythrocyte and kidney ankyrin (Ank1 and
      Ank3, respectively) in vitro. Spectrin binds both Ank1 and Ank3 avidly, as
      expected. Two of the Na,K-ATPase domains, immobilized on a bioaffinity column,
      also interact specifically with both of these ankyrins. These ATPase domains are
      encoded by codons 140-290 (domain II) and 345-784 (domain III), with domain II
      displaying the greatest apparent affinity. Sequences in domain II are highly
      conserved between species and isoforms of Na,K-ATPase and are homologous to a
      cytoplasmic domain in H,K-ATPase and to a limited region of sequence in Ca
      ATPase. Conversely, domain II shares no significant homology with other ankyrin
      binding proteins such as band 3 and Na(+)-channel proteins. These results
      identify a clear function for a conserved but previously not understood region of
      the alpha subunit of Na,K-ATPase and suggest that the interaction of ankyrin with
      membrane transport proteins may involve complex tertiary structural determinants
      not easily deduced from the primary sequence.

PMID- 8159689
TI  - Bone marrow transplantation corrects the enzyme defect in neurons of the central
      nervous system in a lysosomal storage disease.
AB  - Neuronal storage disorders are fatal neurodegenerative diseases of humans and
      animals that are caused by inherited deficiencies of lysosomal hydrolase
      activity. Affected individuals often appear normal at birth but eventually
      develop progressive neurologic symptoms including sensory and motor deficits,
      mental retardation, and seizures. We have examined efficacy of bone marrow
      transplantation as a means of enzyme replacement, using cats with the lysosomal
      storage disease alpha-mannosidosis. Treated animals showed little or no
      progression of neurologic signs 1-2 years after transplant, whereas untreated
      cats became severely impaired and reached endstage disease by 6 months of age.
      Increased lysosomal alpha-mannosidase activity was found in brain tissue of the
      treated animals, and electron microscopy revealed no evidence of lysosomal
      storage within most neurons. Histochemical localization of acidic alpha-D
      mannoside mannohydrolase (EC 3.2. 1.24), using 5-bromo-4-chloro-3-indolyl alpha-D
      mannopyranoside, showed that functional enzyme was present in neurons, glial
      cells, and cells associated with blood vessels. This study provides direct
      evidence that bone marrow transplantation as treatment for a neuronal storage
      disease can lead to significant levels of a missing lysosomal hydrolase within
      neurons of the central nervous system and to compensation for the genetic
      metabolic defect.

PMID- 8159690
TI  - Targeted gene walking by low stringency polymerase chain reaction: assignment of
      a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31.
AB  - We have developed a low stringency polymerase chain reaction (LSPCR) to isolate
      the unknown neighboring region around a known DNA sequence, thus allowing
      efficient targeted gene walking. The method involves the polymerase chain
      reaction (PCR) with a single primer under conditions of low stringency for primer
      annealing (40 degrees C) for the first few cycles followed by more cycles at high
      stringency (55 degrees C). This enables the amplification of a targeted DNA
      fragment along with other nontargeted fragments. High stringency (55 degrees C)
      nested PCRs with end-labeled primers are then used to generate a ladder of
      radioactive bands, which accurately identifies the targeted fragment(s). We
      performed LSPCR on human placental DNA using a highly conserved sodium channel
      specific primer for 5 cycles at 40 degrees C followed by 27 cycles at 55 degrees
      C for primer annealing. Subsequently, using higher stringency (55 degrees C) PCR
      with radiolabeled nested primers for 8 cycles, we have isolated a 0.66-kb
      fragment of a putative human sodium channel gene. Partial sequence (325 bp) of
      this fragment revealed a 270-bp region (exon) with homology to the rat brain
      sodium channel III alpha (RBIII) gene at the nucleotide (87%) and amino acid
      (92%) levels. Therefore, we putatively assign this sequence as a part of a gene
      coding the alpha-subunit of a human brain type III sodium channel (SCN3A). Using
      PCR on two human/rodent somatic cell hybrid panels with primers specific to this
      putative SCN3A gene, we have localized this gene to chromosome 2. Fluorescence in
      situ hybridization to human metaphase chromosomes was used to sublocalize the
      SCN3A gene to chromosome at 2q24-31. In conclusion, LSPCR is an efficient and
      sensitive method for targeted gene walking and is also useful for the isolation
      of homologous genes in related species.

PMID- 8159691
TI  - Reversible inactivation of the Escherichia coli RecBCD enzyme by the
      recombination hotspot chi in vitro: evidence for functional inactivation or loss
      of the RecD subunit.
AB  - Genetic recombination in Escherichia coli is stimulated by a RecBCD enzyme
      mediated event at DNA sequences known as Chi (chi) sites (5'-GCTGGTGG-3').
      Previously, it was shown that chi acts to regulate the nuclease activity of
      RecBCD; here, we demonstrate that, under appropriate conditions, interaction with
      chi sites can also result in an inactivation of helicase activity of RecBCD. The
      unwinding of double-stranded DNA-containing chi sites, under conditions of
      limiting Mg2+ ion, results in the reversible inactivation of RecBCD; addition of
      excess Mg2+ to the reaction reactivates all activities of RecBCD. Inactivation is
      the consequence of a chi-dependent modification of RecBCD that appears to result
      from an inability of the chi-modified RecBCD to reinitiate unwinding of intact
      DNA molecules. This characteristic behavior of RecBCD and chi is displayed by the
      reconstituted RecBC (i.e., without the RecD subunit), except that it is not
      dependent on chi interaction. This biochemical similarity between the chi
      modified RecBCD and RecBC enzymes implies that recognition of chi results in a
      dissociation or functional inactivation of RecD subunit and lends support to the
      hypothesis that interaction with chi results in ejection of the RecD subunit.

PMID- 8159692
TI  - Requirement for a conserved, tertiary interaction in the core of 23S ribosomal
      RNA.
AB  - A putative base-pairing interaction that determines the folding of the central
      region of 23S rRNA has been investigated by mutagenesis. Each of the possible
      base substitutions has been made at the phylogenetically covariant positions
      adenine-1262 (A1262) and U2017 in Escherichia coli 23S rRNA. Every substitution
      that disrupts the potential for Watson-Crick base pairing between these positions
      reduces or abolishes the participation of 23S rRNA in protein synthesis. All
      mutant 23S rRNAs are assembled into 50S subunits, but the mutant subunits are
      less able to stably interact with 30S subunits to form translationally active
      ribosomes. The function of 23S rRNA is largely reestablished by introduction of
      an alternative G1262.C2017 or U1262.A2017 pair, although neither of these
      supports polysome formation quite as effectively as the wild-type pair. A 23S
      rRNA with a C1262.G2017 pair is nonfunctional. In contrast to the considerable
      effect the mutations have on function, they impart only slight structural changes
      on the naked rRNA, and these are limited to the immediate vicinity of the
      mutations. The data show that positions 1262 and 2017 pair in a Watson-Crick
      manner, but the data also indicate that these nucleotides engage in additional
      interactions within the ribosome and that these interactions determine what base
      pairs are acceptable there.

PMID- 8159693
TI  - Association of single-stranded transferred DNA from Agrobacterium tumefaciens
      with tobacco cells.
AB  - During the inception of crown gall tumorigenesis, the transferred DNA (T-DNA) is
      processed from the Ti (tumor inducing) plasmid of Agrobacterium tumefaciens and
      is transferred to plant cells. T-DNA processing and transfer require the
      induction of vir (virulence) genes by phenolic compounds secreted by wounded
      plant cells. After vir gene induction, both single-stranded (T-strands) and
      double-stranded forms of processed T-DNA accumulate in the bacteria. Although
      current models favor the transfer of T-strands to plants, there has yet been no
      experimental evidence to show this. In this paper, we show that T-strands
      disappear from acetosyringone-induced A. tumefaciens within 30 min of bacterial
      cocultivation with tobacco protoplasts. PCR analysis of T-DNA associated with
      protoplasts indicates that single-stranded, but not double-stranded, T-DNA can be
      detected in the plant cells within 30 min of bacterial cocultivation. Control
      experiments show that this T-DNA does not originate from lysed contaminating
      bacterial cells. T-DNA transfer depends on a functional bacterial virB operon.
      Protoplast infections using an A. tumefaciens virE mutant result in a low level
      of accumulation of T-strands in the plant cells.

PMID- 8159694
TI  - Reversible inactivation of visual processing operations in middle suprasylvian
      cortex of the behaving cat.
AB  - Extrastriate visual areas on the banks of the middle suprasylvian sulcus were
      inactivated by cooling to assess the behavioral contribution of this cortical
      region to the extraction of a stationary figure from a moving mask. Cooling
      blocked figure-ground separation when the mask was moving but had no influence
      when the mask was static. This difference provides strong evidence that the areas
      bounding the middle suprasylvian sulcus contribute to the neural separation of
      stationary from moving visual stimuli.

PMID- 8159695
TI  - Adhesion of hard spheres under the influence of double-layer, van der Waals, and
      gravitational potentials at a solid/liquid interface.
AB  - The deposition process of colloidal particles or microorganisms on flat surfaces
      is analyzed by means of computer simulations. Interparticle interactions (double
      layer and van der Waals) and weak gravitational forces are taken into account;
      hydrodynamic interactions, on the other hand, are neglected. In particular, the
      deposition probability as a function of the deposition location of a particle in
      the presence of one or two identical fixed particles is discussed. It is shown,
      in particular, that the ratio of the adhesion probabilities at a given location
      r, for particles subject to weak gravitation, in the presence and in the absence
      of the interparticle interaction U(r) follows approximately a Boltzmann law exp[
      U(r)/kT], even though the adsorption process is fully irreversible. This result
      validates, as far as the distribution function of particles on a surface is
      concerned, Adamczyk's assumption [Adamczyk, Z., Zembala, M., Siwek, B. &
      Warszynski, P. (1990) J. Colloid Interface Sci. 140, 123-137] that the adhesion
      process of Brownian particles can be modeled by a random sequential adsorption
      model with an adsorption probability equal to exp[-U(r)/kT].

PMID- 8159696
TI  - Subunit interaction in the CCAAT-binding heteromeric complex is mediated by a
      very short alpha-helix in HAP2.
AB  - We dissected the domain of HAP2 that mediates subunit association in the
      heteromeric CCAAT-binding complex, first by genetic mutational analysis and then
      by structural studies. The mutational data suggest that a very short region in
      HAP2 mediates protein-protein association and that the structure of this domain
      is likely to be an alpha-helix. The CD analyses of a 15-residue synthetic
      oligopeptide covering this region confirm this surmise. The oligopeptide indeed
      formed an unusually thermal stable alpha-helix in aqueous solution. Eight amino
      acids that lie along one face of this helix, including three arginines, are found
      to be critical for protein-protein association. The partner that interacts with
      this helical motif is likely to be another subunit in the HAP complex, since the
      CCAAT-binding factor is shown to contain one molecule of HAP2. Our results
      suggest that very short regions in proteins can encode precise structures and
      mediate stable and specific protein-protein recognition and interactions.

PMID- 8159697
TI  - Transcytosis in the continuous endothelium of the myocardial microvasculature is
      inhibited by N-ethylmaleimide.
AB  - In a murine heart perfusion system, we were able to "turn off" the transport of
      derivatized albumin [dinitrophenylated albumin (DNP-albumin)] from the perfusate
      to the tissue, by preperfusing the system with 1 mM N-ethylmaleimide (NEM) for 5
      min at 37 degrees C, followed by a 5-min perfusion of DNP-albumin in the presence
      of NEM. Using a postembedding immunocytochemical procedure, we showed that (i) a
      30-sec to 1-min treatment of heart vasculature with 1 mM NEM reduces the
      transendothelial transport of DNP-albumin and nearly stops it after 5 min, and
      (ii) DNP-albumin is detected exclusively in plasmalemmal vesicles (PVs) while in
      transit across endothelial cells. Perfusion with 10 mM dithiothreitol for 1 min
      before NEM prevents the inhibition of vesicular transport. To quantitate the NEM
      effect on vesicular transport inhibition, we developed an ELISA and a dot-blot
      assay for measuring DNP-albumin in supernatants of perfused whole-heart
      homogenates. The results obtained indicate that the treatment of the heart
      vasculature with 1 mM NEM decreases the vesicular transport of DNP-albumin by 78
      80%. Since NEM is known to inhibit the fusion of different types of vesicular
      carriers with their target membranes in other cell types and in in vitro
      reconstituted cellular systems, by alkylating a NEM-sensitive factor, we assume
      that the same mechanism applies in our in situ system. The decrease of vesicular
      transport can be explained by NEM preventing the fusion of recycling vesicles
      with their targets--i.e., the abluminal and luminal domains of the plasmalemma.
      The results open to question previous interpretations from other laboratories
      according to which plasmalemmal vesicles are sessile, immobile structures.

PMID- 8159698
TI  - Chromosomal localization of the callipyge gene in sheep (Ovis aries) using bovine
      DNA markers.
AB  - A mutation causing muscular hypertrophy, with associated leanness and improved
      feed efficiency, has been recently identified in domestic sheep (Ovis aries).
      Preliminary results indicate that an autosomal dominant gene may be responsible
      for this economically advantageous trait. We have exploited the conservation in
      sequence and chromosomal location of DNA markers across Bovidae to map the
      corresponding callipyge locus to ovine chromosome 18 using a battery of bovine
      chromosome 21 markers. Chromosomal localization of the ovine callipyge locus is
      the first step toward positional cloning of the corresponding gene.

PMID- 8159699
TI  - Molecular cloning, sequencing, and functional expression of a cDNA encoding human
      coproporphyrinogen oxidase.
AB  - Coproporphyrinogen oxidase (EC 1.3.3.3) catalyzes the sixth step in the heme
      biosynthetic pathway, the oxidation of coproporphyrinogen III to
      protoporphyrinogen IX. The activity of this enzyme is deficient in the disease
      hereditary coproporphyria. The sequence of the cDNA and predicted amino acid
      sequence of the human coproporphyrinogen oxidase are presented. The human protein
      sequence contains a region completely homologous to that we obtained by
      sequencing an 11-amino acid peptide fragment from purified murine liver
      coproporphyrinogen oxidase. Results of Southern blotting were consistent with the
      presence of a single human coproporphyrinogen oxidase gene, and Northern blotting
      demonstrated one transcript of similar size in erythroid and nonerythroid cell
      lines. Expression of the cDNA coding for the putative mature human
      coproporphyrinogen oxidase in Escherichia coli resulted in a 17-fold increase in
      coproporphyrinogen activity over endogenous activity.

PMID- 8159700
TI  - Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.
AB  - The polyhedral borane ion [n-B20H18]2- reacts with liquid ammonia in the presence
      of a suitable base to produce an apical-equatorial (ae) isomer of the
      [B20H17NH3]3- ion, [1-(2'-B10H9)-2-NH3B10H8]3-. The structure of this product has
      been confirmed by 11B NMR spectroscopy and x-ray crystallography. This species
      undergoes acid-catalyzed rearrangement to an apical-apical (a2) isomer, [1-(1'
      B10H9)-2-NH3B10H8]3-, whose structure has been determined by 11B NMR
      spectroscopy. The sodium salts of both the ae and the a2 isomers of [B20H17NH3]3-
      have been encapsulated within small unilamellar liposomes, composed of distearoyl
      phosphatidylcholine/cholesterol (1:1), and investigated as boron-delivery agents
      for boron neutron capture therapy (BNCT) of cancer. The biodistribution of boron
      was determined after the injection of liposomal suspensions into BALB/c mice
      bearing EMT6 tumors. Both [B20H17NH3]3- isomers exhibited excellent tumor uptake
      and selectivity at very low injected doses, achieving peak tumor boron
      concentrations of 30-40 micrograms of B/g of tissue and tumor/blood boron ratios
      of approximately 5. The enhanced retention of the [B20H17NH3]3- isomers by EMT6
      tumors may be attributed to their facile intracellular oxidation to an extremely
      reactive NH3-substituted [n-B20H18]2- ion, the electrophilic [B20H17NH3]- ion.
      Both isomers of [B20H17NH3]3- are at least 0.5 V more easily oxidized than other
      previously investigated species containing 20 boron atoms. In another experiment,
      [ae-B20H17NH3]3- was encapsulated in liposomes prepared with 5% PEG-2000
      distearoyl phosphatidylethanolamine in the liposome membrane. As expected, these
      liposomes exhibited a longer circulation lifetime in the biodistribution
      experiment, resulting in the continued accumulation of boron in the tumor over
      the entire 48-hr experiment and reaching a maximum of 47 micrograms of B/g of
      tumor.

PMID- 8159701
TI  - Pathogenic potential of human monoclonal immunoglobulin light chains:
      relationship of in vitro aggregation to in vivo organ deposition.
AB  - The deposition of certain Bence Jones proteins as tubular casts, basement
      membrane precipitates, or amyloid fibrils results in the human light-chain
      associated renal and systemic diseases--myeloma (cast) nephropathy, light-chain
      deposition disease, and immunocyte-derived (primary or AL) amyloidosis. To
      determine if light-chain nephrotoxicity or amyloidogenicity is related to the
      propensity of these components to form high molecular weight aggregates under
      physiological conditions, we used a size-exclusion chromatographic system to
      study 40 different Bence Jones proteins. Each samples was tested over a wide
      range of protein concentration in three different buffers varying in pH,
      osmolality, and the presence or absence of low concentrations of urea. Thirty
      three of the 35 proteins found clinically and/or experimentally to form in vivo
      pathologic light-chain deposits were shown to undergo high-order self-association
      and form high molecular weight aggregates. In contrast, of five nonpathologic
      proteins, one showed polymerization under the chromatographic conditions used.
      The correlation between the in vivo results achieved by size-exclusion
      chromatography and that found in vivo provides (i) a rapid diagnostic method to
      identify potential nephrotoxic or amyloidogenic Bence Jones proteins and (ii) an
      experimental means to gain new insight into the physicochemical basis of light
      chain aggregation and the treatment of those invariably fatal disorders
      associated with pathologic light-chain deposition.

PMID- 8159702
TI  - Dantrolene ameliorates the metabolic hallmarks of sepsis in rats and improves
      survival in a mouse model of endotoxemia.
AB  - Sepsis is the systemic inflammatory response resulting from serious infection and
      is the most common cause of death in intensive care units. Intracellular free
      calcium concentration ([Ca2+]i) is an important regulator of numerous cellular
      processes and when increased excessively may act as a potent cellular toxin. To
      determine if [Ca2+]i is responsible for the major metabolic changes which are
      hallmarks of sepsis, we examined if sodium dantrolene, a drug which decreases
      release of calcium from sarcoplasmic reticulum, affected the metabolic
      abnormalities in plasma and epitrochlearis muscles of rats made septic by cecal
      ligation and perforation. Dantrolene when added in vitro or when given in vivo
      decreases many of the metabolic hallmarks of sepsis--i.e., muscle protein
      breakdown approximately 30%, muscle glucose transport approximately 38%, muscle
      lactate formation approximately 28%, and plasma lactate approximately 29% (P <
      0.05). In addition, we examined the ability of dantrolene to improve survival in
      a mouse model of endotoxemia. Dantrolene caused > 2-fold improvement in survival
      when it was administered concurrently with endotoxin (54% vs. 20% survival in
      dantrolene-treated and control mice, respectively (P < 0.001). Our results are
      consistent with the hypothesis that an increase in [Ca2+]i plays an important
      role in the metabolic abnormalities which occur during sepsis and that dantrolene
      administration may be an effective therapeutic strategy.

PMID- 8159703
TI  - Yeast farnesyl-diphosphate synthase: site-directed mutagenesis of residues in
      highly conserved prenyltransferase domains I and II.
AB  - Prenyltransferases that catalyze the fundamental chain elongation reaction in the
      isoprenoid biosynthetic pathway contain several highly conserved amino acids,
      including two aspartate-rich regions thought to be involved in substrate binding
      and catalysis. We report a study of site-directed mutants for yeast farnesyl
      diphosphate synthase (FPPSase; geranyl-diphosphate:isopentenyl-diphosphate, EC
      2.5.1.10), a prenyltransferase that catalyzes the sequential 1'-4 coupling of
      isopentenyl diphosphate (IPP) with dimethylallyl diphosphate and geranyl
      diphosphate. A recombinant form of FPPSase extended by a C-terminal -Glu-Glu-Phe
      alpha-tubulin epitope (EEF in single-letter amino acid code) was engineered to
      facilitate rapid purification of the enzyme by immunoaffinity chromatography and
      to remove traces of contaminating activity from wild-type FPPSase in the
      Escherichia coli host. Ten site-directed mutants were constructed in
      FPPSase::EEF. The six aspartates in domain I (at positions 100, 101, and 104) and
      domain II (at positions 240, 241, and 244) were changed to alanine (mutants
      designated D100A, D101A, D104A, D240A, D241A, and D244A); three arginine residues
      were changed, Arg-109 and Arg-110 to glutamine and Arg-350 to alanine (mutants
      designated R109Q, R110Q, and R350A); and Lys-254 was converted to alanine (mutant
      designated K254A). Mutations of the aspartatic residues and nearby arginine
      residues in domain I and Asp-240 and Asp-241 in domain II drastically lowered the
      catalytic activity of FPPSase::EEF. The D244A and K254A mutants were
      substantially less active, while kcat and the Michaelis constants for the R350A
      mutant were similar to those of FPPSase::EEF. Addition of an -EEF epitope to the
      C terminus of wild-type FPPSase resulted in a 14-fold increase of KmIPP and a 12
      fold decrease of kcat, suggesting that the conserved hydrophilic C terminus of
      the enzyme may have a role in substrate binding and catalysis.

PMID- 8159704
TI  - Vertical versus planar neural induction in Rana pipiens embryos.
AB  - The neural plate in the amphibian embryo is induced in the ectoderm by signals
      from the dorsal mesoderm. In the extensively studied species Xenopus laevis, such
      signals are believed to proceed along two alternate pathways, defined as vertical
      and planar induction. We have studied the relative importance of these pathways
      in Rana pipiens. In the embryo of this frog, dorsal mesoderm involution can be
      diverted from its normal course by injection of peptides that inhibit interaction
      of fibronectin with its receptor. In such embryos, dorsal mesoderm failed to
      migrate across the blastocoel roof but moved bilaterally along the equator,
      leading to the formation of two notochords. Neural tissue differentiation
      occurred in close association with each notochord, but no neural tissue formed
      along the dorsal midline as might have been predicted by a predominantly planar
      induction model. While in X. laevis planar induction has been reported to be a
      major pathway in neuralizing the ecoderm, the results presented here indicate
      that vertical induction predominates in initiating neural development in R.
      pipiens embryos.

PMID- 8159705
TI  - Gene therapy for brain tumors: regression of experimental gliomas by adenovirus
      mediated gene transfer in vivo.
AB  - The therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine
      kinase (HSV-tk) gene transduction of rat C6 glioma cells followed by ganciclovir
      (GCV) administration was studied in tumors generated in the brains of nude mice.
      C6 glioma cells were efficiently transduced in vitro by a replicative-defective
      recombinant adenovirus carrying the HSV-tk gene (ADV/RSV-tk) that rendered them
      sensitive to GCV in a dose-dependent manner. Tumors were generated by stereotaxic
      intracerebral injection of 1 x 10(4) C6 cells in nude mice. After 8 days of tumor
      growth, 3 x 10(8) ADV/RSV-tk viral particles were injected into the tumors and
      the mice subsequently were treated with GCV for 6 days. Tumor size in untreated
      and treated animals was compared 20 days after tumor implantation. The mean cross
      sectional area of the tumors in the treated animals was 23-fold smaller than in
      control animals and the tumor volume was reduced by > 500-fold. These results
      demonstrate that the recombinant adenoviral vector can function as an efficient
      gene delivery vehicle for the treatment of gliomas by in vivo gene therapy.

PMID- 8159706
TI  - Synaptic disinhibition during maintenance of long-term potentiation in the CA1
      hippocampal subfield.
AB  - Long-term potentiation (LTP) in the CA1 region of the hippocampus is widely
      believed to occur through a strengthening of efficacy of excitatory synapses
      between afferent fibers and pyramidal cells. An alternative mechanism of LTP,
      reduction of efficacy of synaptic inhibition, was examined in the present report.
      The present study demonstrates that the maintenance of LTP in the CA1 hippocampal
      subfield of guinea pigs is accompanied by impairment of type A gamma-aminobutyric
      acid (GABA) receptor function, particularly at apical dendritic sites of CA1
      pyramidal cells. Enhanced excitability of GABAergic interneurons during LTP
      represents a strengthening of inhibitory efficacy. The net effect of opposite
      modifications of synaptic inhibition during LTP of CA1 pyramidal cells is an
      overall impairment of the strength of GABAergic inhibition, and disinhibition
      could contribute importantly to CA1 pyramidal cell LTP.

PMID- 8159707
TI  - Identification of a brefeldin A-insensitive guanine nucleotide-exchange protein
      for ADP-ribosylation factor in bovine brain.
AB  - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide
      binding proteins that participate in vesicular transport in the Golgi and other
      intracellular compartments and stimulate cholera toxin ADP-ribosyltransferase
      activity. ARFs are active in the GTP-bound form; hydrolysis of bound GTP to GDP,
      possibly with the assistance of a GTP hydrolysis (GTPase)-activating protein
      results in inactivation. Exchange of GDP for GTP and reactivation were shown by
      other workers to be enhanced by Golgi membranes in a brefeldin A-sensitive
      reaction, leading to the proposal that the guanine nucleotide-exchange protein
      (GEP) was a target of brefeldin A. In the studies reported here, a soluble GEP
      was partially purified from bovine brain. Exchange of nucleotide on ARFs 1 and 3,
      based on increased ARF activity in a toxin assay and stimulation of binding of
      guanosine 5'-[gamma-[35S]thio]triphosphate, was dependent on phospholipids, with
      phosphatidylserine being more effective than cardiolipin. GEP appeared to
      increase the rate of nucleotide exchange but did not affect the affinity of ARF
      for GTP. Whereas the crude GEP had a size of approximately 700 kDa, the partially
      purified GEP behaved on Ultrogel AcA 54 as a protein of 60 kDa. With
      purification, the GEP activity became insensitive to brefeldin A, consistent with
      the conclusion that, in contrast to earlier inferences, the exchange protein is
      not itself the target of brefeldin A.

PMID- 8159709
TI  - Enhanced DNA sequencing by hybridization.
AB  - An enhanced version of DNA sequencing by hybridization (SBH), termed positional
      SBH (PSBH), has been developed. PSBH uses duplex probes containing single
      stranded 3' overhangs, instead of simple single-stranded probes. Stacking
      interactions between the duplex probe and a single-stranded target should provide
      enhanced stringency in distinguishing perfectly matched 3' sequences. A second
      enhancement is the use of enzyme-catalyzed steps, instead of pure physical
      hybridization. The feasibility of this scheme has been investigated using
      biotinylated duplex probes containing single-stranded 5-base 3' overhangs,
      immobilized on streptavidin-coated magnetic beads. Ligation of a single-stranded
      target, hybridized to the single-stranded region of the duplex probes, provided
      enhanced discrimination of perfectly matched targets from those containing
      mismatches. In distinction to the serious complications caused by base
      composition effects in ordinary SBH, there was little effect of base composition
      in PSBH. The hardest mismatch to discriminate was the one furthest from the
      phosphodiester bond formed by ligation. However, mismatches in this position were
      efficiently discriminated by 3' extension of the duplex probe using a template
      dependent DNA polymerase. These results demonstrate that PSBH offers considerable
      promise to facilitate actual implementations of SBH.

PMID- 8159708
TI  - The retinoid X receptor ligand, 9-cis-retinoic acid, is a potential regulator of
      early Xenopus development.
AB  - Endogenous retinoids are potential regulators of vertebrate embryogenesis that
      have been implicated in early anterior-posterior patterning and limb-bud
      development. We have characterized the temporal and spatial distribution of 9-cis
      retinoic acid in the Xenopus embryo and compared it to two other retinoids, all
      trans-retinoic acid and all-trans-retinoyl-beta-glucuronide. 9-cis-Retinoic acid
      is first detected after the midblastula transition and by the end of gastrulation
      is localized primarily within the anterior and posterior dorsal regions of the
      embryo. Since 9-cis-retinoic acid is a 6-fold more potent dysmorphogen than trans
      retinoic acid, we suggest that it is involved in the early specification of the
      Xenopus anterior-posterior axis.

PMID- 8159710
TI  - Electrophysiological properties of newborn and adult rat spinal cord glycine
      receptors expressed in Xenopus oocytes.
AB  - The properties of glycine receptors (GlyRs) from newborn and adult rat spinal
      cord were studied in Xenopus oocytes injected with whole mRNA or the heavy (H) or
      light (L) mRNA fractions encoding their respective GlyRs. Mean open times and
      conductances of channels gated by H- or L-GlyRs were determined by noise analysis
      or voltage jumps. We found that adult H- and L-GlyRs opened channels that
      differed in their mean open time but had the same channel conductance. Both H-
      and L-GlyRs gated Cl- currents that displayed a similarly strong outward
      rectification. Nevertheless, single channels of adult H- and L-GlyRs did not
      rectify and their mean open times were only slightly altered by voltage. It
      follows that the outward rectification of adult GlyRs is due mainly to a
      reduction in the number of open channels. In contrast to H-GlyRs, whose
      characteristics seem to remain essentially unchanged with age, L-GlyRs from
      newborn and adult rats have different properties. Channels of newborn L-GlyRs
      have a higher conductance, longer open time, and greater voltage dependency than
      those from the adult. Interestingly, properties of newborn GlyRs expressed by
      whole mRNA were markedly different from those encoded by newborn or adult L or H
      mRNA. These results demonstrate that the functional heterogeneity of GlyRs is
      developmentally regulated.

PMID- 8159711
TI  - ATP-dependent phosphorylation of serine-46 in the phosphocarrier protein HPr
      regulates lactose/H+ symport in Lactobacillus brevis.
AB  - Lactobacillus brevis takes up lactose and the nonmetabolizable lactose analogue
      thiomethyl beta-galactoside (TMG) by a permease-catalyzed lactose/H+ symport
      mechanism. Earlier studies have shown that TMG, previously accumulated in L.
      brevis cells, rapidly effluxes from the cells upon addition of glucose, and that
      glucose inhibits further uptake of TMG. We have developed a vesicular system to
      analyze this regulatory mechanism and have used electroporation to shock proteins
      and membrane-impermeant metabolites into the vesicles. Uptake of TMG was
      dependent on an energy source, effectively provided by intravesicular ATP or
      extravesicular arginine. TMG uptake into these vesicles was not inhibited, and
      preaccumulated TMG did not efflux from them upon addition of glucose.
      Intravesicular but not extravesicular wild-type phosphocarrier protein HPr of
      Bacillus subtilis restored regulation. Glucose could be replaced by
      intravesicular (but not extravesicular) fructose 1,6-bisphosphate, gluconate 6
      phosphate, or 2-phosphoglycerate, but not by other phosphorylated metabolites, in
      agreement with the allosteric activating effects of these compounds on HPr(Ser)
      kinase measured in vitro. Intravesicular serine-46-->alanine mutant HPr cold not
      promote regulation of lactose permease activity when electroporated into the
      vesicles with or without glucose or the various phosphorylated metabolites, but
      the serine-46-->aspartate mutant HPr promoted regulation, even in the absence of
      glucose or a metabolite. HPr(Ser-P) appears to convert the lactose/H+ symporter
      into a sugar uniporter. These results establish that HPr serine phosphorylation
      by the ATP-dependent metabolite-activated HPr kinase regulates lactose permease
      activity in L. brevis. A direct allosteric mechanism is proposed.

PMID- 8159712
TI  - Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter
      analysis, and chromosomal localization.
AB  - Peroxisomal acyl-CoA oxidase (ACOX; EC 1.3.3.6) is the first enzyme of the fatty
      acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2
      trans-enoyl-CoAs, and it donates electrons directly to molecular oxygen, thereby
      producing H2O2. The discovery of carcinogenic peroxisome proliferators, which
      markedly increase the levels of this H2O2-producing ACOX in rat and mouse liver,
      generated interest in peroxisomal beta-oxidation system genes. The present study
      deals with the structural organization of human ACOX gene. This gene spans
      approximately 33 kb and consists of 14 exons and 13 introns. Primer-extension
      analysis revealed three principal cap sites, which were mapped at 50, 52, and 53
      nt upstream of the initiator methionine codon. The 5' flanking region of the ACOX
      gene was sequenced up to 500 bp upstream of the cap sites. This promoter region
      is G + C-rich and contains three copies of the "GC box" hexanucleotides. Multiple
      GC boxes are a characteristic feature of the rat ACOX and bifunctional protein
      genes of the beta-oxidation system. A + T-rich TATA-boxlike sequences, TTTATTT
      and TTATT, have also been identified in this human ACOX gene, but typical CCAAT
      motifs are absent. This ACOX gene has been mapped to chromosome 17q25 by in situ
      hybridization, using a biotinlabeled probe.

PMID- 8159713
TI  - Alpha-crystallin/small heat shock protein has autokinase activity.
AB  - The alpha-crystallins (alpha A and alpha B) are major water-soluble proteins of
      the transparent eye lens that are expressed in a variety of tissues and can
      function as molecular chaperones. alpha B-crystallin is also a small heat shock
      protein associated with numerous degenerative diseases and abnormal growth
      patterns. Previous experiments have shown that alpha A-and alpha B-crystallin are
      phosphorylated on specific serine residues by a cAMP-dependent pathway. Here we
      provide evidence that either total bovine alpha-crystallin or its isolated
      polypeptides can autophosphorylate serine by a cAMP-independent mechanism in the
      presence of Mg2+ and [gamma-32P]ATP; the autophosphorylated products
      isoelectrically focus with the authentic phosphorylated forms of the alpha
      crystallin polypeptides. Thus, the alpha A- and alpha B-crystallin/small heat
      shock protein polypeptides are enzyme-crystallins which may be involved in
      metabolic pathways important for the development, maintenance, or pathology of
      the lens and other tissues.

PMID- 8159714
TI  - Biosynthesis of lipooligosaccharide nodulation factors: Rhizobium NodA protein is
      involved in N-acylation of the chitooligosaccharide backbone.
AB  - Rhizobium meliloti interacts symbiotically with alfalfa by forming root nodules
      in which the bacteria fix nitrogen. The Rhizobium nodulation genes nodABC are
      involved in the synthesis of lipooligosaccharide symbiotic signal molecules,
      which are mono-N-acylated chitooligosaccharides. These bacterial signals elicit
      nodule organogenesis in roots of legumes. To elucidate the role of the NodA
      protein in lipooligosaccharide biosynthesis, we prepared a radiolabeled
      tetrasaccharide precursor carrying an amino group as a potential attachment site
      for N-acylation at the nonreducing glucosamine residue. Various criteria
      demonstrate that NodA is involved in the attachment of a fatty acyl chain to this
      tetrasaccharide precursor, yielding a biologically active nodulation factor.

PMID- 8159715
TI  - Domain swapping: entangling alliances between proteins.
AB  - The comparison of monomeric and dimeric diphtheria toxin (DT) reveals a mode for
      protein association which we call domain swapping. The structure of dimeric DT
      has been extensively refined against data to 2.0-A resolution and a three-residue
      loop has been corrected as compared with our published 2.5-A-resolution
      structure. The monomeric DT structure has also been determined, at 2.3-A
      resolution. Monomeric DT is a Y-shaped molecule with three domains: catalytic
      (C), transmembrane (T), and receptor binding (R). Upon freezing in phosphate
      buffer, DT forms a long-lived, metastable dimer. The protein chain tracing
      discloses that upon dimerization an unprecedented conformational rearrangement
      occurs: the entire R domain from each molecule of the dimer is exchanged for the
      R domain from the other. This involves breaking the noncovalent interactions
      between the R domain and the C and T domains, rotating the R domain by 180
      degrees with atomic movements up to 65 A, and re-forming the same noncovalent
      interactions between the R domain and the C and T domains of the other chain of
      the dimer. This conformational transition explains the long life and
      metastability of the DT dimer. Several other intertwined, dimeric protein
      structures satisfy our definition of domain swapping and suggest that domain
      swapping may be the molecular mechanism for evolution of these oligomers and
      possibly of oligomeric proteins in general.

PMID- 8159716
TI  - Isolation and analysis of the breakpoint sequences of chromosome inversion
      In(3L)Payne in Drosophila melanogaster.
AB  - Chromosomal rearrangements constitute a significant feature of genome evolution,
      and inversion polymorphisms in Drosophila have been studied intensely for
      decades. Population geneticists have long recognized that the sequence features
      associated with inversion breakpoints would reveal much about the mutational
      origin, uniqueness, and genealogical history of individual inversion
      polymorphisms, but the cloning of breakpoint sequences is not trivial. With the
      aid of a method for rapid recovery of DNA clones spanning rearrangement
      breakpoints, we recover and examine the DNA sequences spanning the breakpoints of
      the cosmopolitan inversion In(3L)Payne in Drosophila melanogaster. By examining
      the sequence diversity associated with six standard and seven inverted
      chromosomes from natural populations, we find that the inversion is monophyletic
      in origin, the sequences are genetically isolated from recombination at the
      breakpoints, and there is no association with features such as transposable
      elements. The inverted sequences show 17-fold less nucleotide polymorphism, but
      there are eight fixed differences in the region spanning both breakpoints. This
      suggests that this inversion is not recently derived. Finally, Northern analysis
      and transcript mapping find that the distal breakpoint has disrupted three
      transcripts that are normally expressed in the standard arrangement.
      Incidentally, the method introduced here can be used to isolate breakpoint
      sequences of arrangements associated with many human diseases.

PMID- 8159717
TI  - Anticarcinogenic activities of sulforaphane and structurally related synthetic
      norbornyl isothiocyanates.
AB  - Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl)butane] was recently isolated
      from one variety of broccoli as the major and very potent inducer of phase 2
      detoxication enzymes in murine hepatoma cells in culture. Since phase 2 enzyme
      induction is often associated with reduced susceptibility of animals and their
      cells to the toxic and neoplastic effects of carcinogens and other electrophiles,
      it was important to establish whether sulforaphane could block chemical
      carcinogenesis. In this paper we report that sulforaphane and three synthetic
      analogues, designed as potent phase 2 enzyme inducers, block the formation of
      mammary tumors in Sprague-Dawley rats treated with single doses of 9,10-dimethyl
      1,2-benzanthracene. The analogues are exo-2-acetyl-exo-6
      isothiocyanatonorbornane, endo-2-acetyl-exo-6-isothiocyanatonorbornane, and exo-2
      acetyl-exo-5-isothiocyanatonorbornane. When sulforaphane and exo-2-acetyl-exo-6
      isothiocyanatonorbornane were administered by gavage (75 or 150 mumol per day for
      5 days) around the time of exposure to the carcinogen, the incidence,
      multiplicity, and weight of mammary tumors were significantly reduced, and their
      development was delayed. The analogues endo-2-acetyl-exo-6
      isothiocyanatonorbornane and exo-2-acetyl-exo-5-isothiocyanatonorbornane were
      less potent protectors. Thus, a class of functionalized isothiocyanates with
      anticarcinogenic properties has been identified. These results validate the
      thesis that inducers of phase 2 enzymes in cultured cells are likely to protect
      against carcinogenesis.

PMID- 8159718
TI  - Mutational analysis of the N-terminal topogenic signal of watermelon glyoxysomal
      malate dehydrogenase using the heterologous host Hansenula polymorpha.
AB  - We have studied the significance of the N-terminal presequence of watermelon
      (Citrullus vulgaris) glyoxysomal malate dehydrogenase [gMDH; (S)-malate:NAD+
      oxidoreductase; EC 1.1.1.37] in microbody targeting. The yeast Hansenula
      polymorpha was used as heterologous host for the in vivo expression of various
      genetically altered watermelon MDH genes, whose protein products were localized
      by immunocytochemical techniques. It is shown that the presequence of gMDH is
      essential and sufficient for peroxisomal targeting; it can target the mature part
      of the mitochondrial MDH to microbodies, whereas deletion of the presequence
      results in accumulation of the mature form of gMDH in the cytosol. Alignment of
      the N termini of several peroxisomal proteins that are assumed to contain a
      peroxisomal targeting signal at the N terminus (PTS2) suggested the consensus
      seqence RL-X5-HL. A similar motif is present in the presequence of watermelon
      gMDH--namely, 10RI-X5-17HL. Mutational analysis revealed that substitutions of
      10RI into DD or 17HL into DE destroyed the topogenic information, whereas
      substitutions of 25M into I and 26EE into LV did not. By combining our data with
      recent analyses of others on the presequences of mammalian thiolases, it is
      concluded that the peroxisomal targeting information of PTS2 is contained in the
      consensus sequence RL/I-X5-HL. In contrast to the higher plant and mammals, the
      Hansenula yeast peroxisomes seem to lack an enzyme capable of removing microbody
      presequences of higher eukaryotes.

PMID- 8159719
TI  - Electron micrographic studies of transport of oligodeoxynucleotides across
      eukaryotic cell membranes.
AB  - Unmodified oligodeoxynucleotides (ODNs) were synthesized and tested for their
      ability to cross external eukaryotic cell membranes and to enter the cytosol and
      nucleus in tissue cultures. The ODNs were labeled with high-specific-activity
      [3H]thymidine (> or = 100 Ci/mmol), or [ alpha-32P]ATP or [ gamma-32P]ATP (300
      1000 Ci/mmol; 1 Ci = 37 GBq), and the label was either in the central portion of
      the molecule or at the 3' or 5' end. The cells employed were for the most part
      3T6 murine fibroblasts, grown in monolayers, either semiconfluent or confluent,
      but some experiments were carried out with chicken embryo fibroblasts or human
      HeLa cells. Parallel wells in the same experiment were prepared for electron
      microscopy or for cell fractionation and radioactivity assays. Electron
      microscopic autoradiography indicated that ODNs cross the external cell membrane,
      traverse the cytosol, and begin to enter the cell nucleus within a few seconds to
      5 min at 37 degrees C in Dulbecco's medium without added serum. After 30-60 min
      of incubation with ODNs, abundant silver grains were observed at or just inside
      the nuclear membrane or well distributed across the nucleus, particularly in
      association with euchromatin. There was a paucity of silver grains associated
      with nucleoli. Cell entry of oligomer was related to cell cycling events and was
      energy dependent. Degradation of oligomer to monomers, with reincorporation into
      DNA, does not appear to explain these results. No sequestration of labeled
      oligomer in cytoplasmic vesicles en route from the exterior of the cell to the
      nucleus was observed. The observations are more suggestive of internalization of
      oligonucleotide by a mechanism as yet unclear or, alternatively, by a caveolar,
      potocytotic mechanism rather than by endocytosis.

PMID- 8159720
TI  - Mutational processes of simple-sequence repeat loci in human populations.
AB  - Mutational processes of simple sequence repeats (SSRs) in complex genomes are
      poorly understood. We examined these processes by introducing a two-phase
      mutation model. In this model, most mutations are single-step changes, but
      infrequent large jumps in repeat number also occur. We used computer simulations
      to determine expected values of statistics that reflect frequency distributions
      of allele size for the two-phase model and two alternatives, the one-step and
      geometric models. The theoretical expectations for each model were tested by
      comparison with observed values for 10 SSR loci genotyped in the Sardinian
      population, whose genetic and demographic histories have been previously
      reconstructed. The two-phase model provided the best fit to the data for most of
      these loci in this population. In the analysis we assumed that the loci were
      neutral and that this population had undergone rapid population growth. Recent
      observations made for unstable trinucleotide repeats support our suggestion that
      frequent small changes and rare large changes in repeat number represent two
      distinct classes of mutation at SSR loci. We genotyped the same 10 loci in
      Egyptian and sub-Saharan African samples to assess the utility of SSRs for
      studying the divergence of populations and found that estimates of
      interpopulation distances from SSRs were similar to those derived from analysis
      of mitochondrial DNA.

PMID- 8159721
TI  - Formation of in vivo complexes between the TAL1 and E2A polypeptides of leukemic
      T cells.
AB  - Tumor-specific activation of the TAL1 gene occurs in approximately 25% of
      patients with T-cell acute lymphoblastic leukemia (T-ALL). The TAL1 gene products
      possess a basic helix-loop-helix (bHLH) domain that interacts in vitro with the
      bHLH proteins (E12 and E47) encoded by the E2A locus. We have now applied two
      independent methods, the two-hybrid procedure and co-immunoprecipitation
      analysis, to demonstrate that TAL1 and E2A polypeptides also associate in vivo.
      These studies show that the bHLH domain of TAL1 selectively interacts with the
      bHLH domains of E12 and E47, but not with the Id1 helix-loop-helix protein. TAL1
      does not self-associate to form homodimeric complexes, implying that the in vivo
      functions of TAL1 depend on heterologous interaction with other bHLH proteins
      such as E12 and E47. Co-immunoprecipitation analysis revealed the presence of
      endogenous TAL1/E2A complexes in Jurkat cells, a leukemic line derived from a T
      ALL patient. Thus, the malignant properties of TAL1 may be due to obligate
      interaction with the E2A polypeptides.

PMID- 8159723
TI  - Overexpression of urokinase-type plasminogen activator in transgenic mice is
      correlated with impaired learning.
AB  - Transgenic mice designated alpha MUPA overproduce in the brain murine urokinase
      type plasminogen activator (uPA), an extracellular protease implicated in tissue
      remodeling. We have now localized, by in situ hybridization, extensive signal of
      uPA mRNA in the alpha MUPA cortex, hippocampus, and amygdala, sites that were not
      labeled in counterpart wild-type mice. Furthermore, biochemical measurements
      reveal a remarkably high level of enzymatic activity of uPA in the cortex and
      hippocampus of alpha MUPA compared with wild-type mice. We have used the alpha
      MUPA mice to examine whether the abnormal level of uPA in the cortex and the
      limbic system affects learning ability. We report that alpha MUPA mice perform
      poorly in tasks of spatial, olfactory, and taste-aversion learning, while
      displaying normal sensory and motor capabilities. Our results suggest that uPA is
      involved in neural processes subserving a variety of learning types.

PMID- 8159722
TI  - Expression of apolipoprotein serum amyloid A mRNA in human atherosclerotic
      lesions and cultured vascular cells: implications for serum amyloid A function.
AB  - Altered lipoprotein metabolism and vascular injury are considered to be major
      parts of the pathogenesis of atherosclerotic lesions. Serum amyloid A (SAA) is a
      family of acute-phase reactants found residing mainly on high density
      lipoproteins (HDL) in the circulation. Several functions for the SAAs have been
      proposed that could be important in atherosclerosis. These include involvement in
      cholesterol metabolism, participation in detoxification, depression of immune
      responses, and interference with platelet functions. Like other acute-phase
      reactants, the liver is a major site of SAA synthesis. However, studies in the
      mouse have revealed that several cell types including macrophages express SAA.
      Furthermore, we recently found that SAA mRNA expression can be induced in the
      human monocyte/macrophage cell line, THP-1. In the present study, human
      atherosclerotic lesions of coronary and carotid arteries were examined for
      expression of SAA mRNA by in situ hybridization. Surprisingly, SAA mRNA was found
      in most endothelial cells and some smooth muscle cells as well as macrophage
      derived "foam cells," adventitial macrophages, and adipocytes. In addition,
      cultured smooth muscle cells expressed SAA1, SAA2, and SAA4 mRNAs when treated
      with interleukin 1 or 6 (IL-1 or IL-6) in the presence of dexamethasone. These
      findings give further credence to the notion that the SAAs are involved in lipid
      metabolism or transport at sites of injury and in atherosclerosis or may play a
      role in defending against viruses or other injurious agents such as oxidized
      lipids. Furthermore, expression of SAAs by endothelial cells is compatible with
      the evidence that SAA modulates platelet aggregation and function and possibly
      adhesion at the endothelial cell surface.

PMID- 8159724
TI  - Electrically conducting polymers can noninvasively control the shape and growth
      of mammalian cells.
AB  - Electrically conducting polymers are novel in that their surface properties,
      including charge density and wettability, can be reversibly changed with an
      applied electrical potential. Such properties might render conducting polymers
      unique for biological applications. However, the majority of research on
      conducting polymers has been carried out under nonbiological conditions. We
      synthesized optically transparent polypyrrole thin films and studied them in
      environments suitable for protein adsorption and mammalian cell culture. In vitro
      studies demonstrated that extracellular matrix molecules, such as fibronectin,
      adsorb efficiently onto polypyrrole thin films and support cell attachment under
      serum-free conditions. When aortic endothelial cells were cultured on fibronectin
      coated polypyrrole (oxidized) in either chemically defined medium or the presence
      of serum, cells spread normally and synthesized DNA. In contrast, when the
      polymer was switched to its neutral state by applying an electrical potential,
      both cell extension and DNA synthesis were inhibited without affecting cell
      viability. Application of a similar electrical potential to cells cultured on
      indium tin oxide surfaces had no effect on cell shape or function. These data
      suggest that electrically conducting polymers may represent a type of culture
      substrate which could provide a noninvasive means to control the shape and
      function of adherent cells, independent of any medium alteration.

PMID- 8159725
TI  - Homologous pairing and strand exchange promoted by the Escherichia coli RecT
      protein.
AB  - RecT protein of Escherichia coli promotes the formation of joint molecules
      between homologous linear double-stranded M13mp19 replicative-form bacteriophage
      DNA and circular single-stranded M13mp19 DNA in the presence of exonuclease VIII,
      the recE gene product. The joint molecules were formed by a mechanism involving
      the pairing of the complementary strand of the linear double-stranded DNA
      substrate with the circular single-stranded DNA substrate coupled with the
      displacement of the noncomplementary strand. When the homologous linear double
      stranded DNA substrate had homologous 3' or 5' single-stranded tails, then RecT
      promoted homologous pairing and strand exchange in the absence of exonuclease
      VIII. Histone H1 could substitute for RecT protein; however, joint molecules
      formed in the presence of histone H1 did not undergo strand exchange. These
      results indicate that under the reaction conditions used, the observed strand
      exchange reaction is promoted by RecT and is not the result of spontaneous branch
      migration. These results are consistent with the observation that expression of
      RecE (exonuclease VIII) and RecT substitutes for RecA in some recombination
      reactions in E. coli.

PMID- 8159726
TI  - Nuclear import of Agrobacterium VirD2 and VirE2 proteins in maize and tobacco.
AB  - Previously, we have shown that Agrobacterium-plant cell transferred DNA (T-DNA)
      transport into the host cell nucleus is likely mediated by two specific bacterial
      proteins, VirD2 and VirE2. Here, we used these proteins to study molecular
      pathways of nuclear import. First, the role of VirE2 nuclear localization signals
      (NLSs) in the T-DNA transport pathway was examined by using tobacco plants
      transgenic for deletion mutants of VirE2. In these plants, the virulence of wild
      type Agrobacterium was reduced possibly by competition for the cellular nuclear
      import machinery. Second, we analyzed the nuclear localization of VirE2 and VirD2
      in the nonhost monocot maize. Part of the known recalcitrance of monocots to
      transformation by Agrobacterium could be due to a potential selectivity in
      nuclear import pathways in monocotyledonous and dicotyledonous plants. Nuclear
      transport of VirD2 and VirE2 in maize leaves and roots was compared to that in
      tobacco protoplasts and roots. Both proteins accumulated in maize leaf and
      tobacco protoplast nuclei as well as in nuclei of immature root cells. In
      contrast, VirD2 and VirE2 expressed in mature roots of maize and tobacco remained
      cytoplasmic. Point mutations of VirE2 nuclear localization signals, NSE 1 and NSE
      2, also revealed that, in maize, the NSE 1 signal was mainly responsible for
      nuclear import; in contrast, both signals functioned independently in tobacco
      protoplasts.

PMID- 8159727
TI  - Glutamate regulates intracellular calcium and gene expression in oligodendrocyte
      progenitors through the activation of DL-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors.
AB  - Oligodendrocytes and their progenitors (O-2A) express functional kainate- and DL
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring
      glutamate receptors. The physiological consequences of activation of these
      receptors were studied in purified rat cortical O-2A progenitors and in the
      primary oligodendrocyte cell line CG-4. Changes in the mRNA levels of a set of
      immediate early genes were studied and were correlated to intracellular Ca2+
      concentration, as measured by fura-2 Ca2+ imaging. Both in CG-4 and in cortical O
      2A progenitors, basal mRNA levels of NGFI-A were much higher than c-fos, c-jun,
      or jun-b. Glutamate, kainate, and AMPA greatly increased NGFI-A mRNA and protein
      by activation of membrane receptors in a Ca(2+)-dependent fashion. Agonists at
      non-N-methyl-D-aspartate receptors promoted transmembrane Ca2+ influx through
      voltage-dependent channels as well as kainate and/or AMPA channels. The influx of
      Ca2+ ions occurring through glutamate-gated channels was sufficient by itself to
      increase the expression of NGFI-A mRNA. AMPA receptors were found to be directly
      involved in intracellular Ca2+ and NGFI-A mRNA regulation, because the effects of
      kainate were greatly enhanced by cyclothiazide, an allosteric modulator that
      selectively suppresses desensitization of AMPA but not kainate receptors. Our
      results indicate that glutamate acting at AMPA receptors regulates immediate
      early gene expression in cells of the oligodendrocyte lineage by increasing
      intracellular calcium. Consequently, modulation of these receptor channels may
      have immediate effects at the genomic level and regulate oligodendrocyte
      development at critical stages.

PMID- 8159728
TI  - Precursors of the neurosteroids.
AB  - In addition to the neurosteroids pregnenolone and dehydroepiandrosterone, organic
      solvent extracts of rat brains contain related compounds that react with various
      reagents to yield additional amounts of these ketosteroids. Among the chemicals
      producing these increments are triethylamine, HCl, FeCl3, and Pb(OAc)4. Most
      revealing is the action of FeSO4 on these extracts. This reducing agent also
      converts components of the extract into the two neurosteroids, suggesting the
      presence of sterol hydroperoxides or peroxides in brain. The clues provided by
      this study indicate that the chemical nature of the steroidal constituents
      existing in extracts of mammalian brains remains to be determined. It is likely
      that their association with neurological functions will be better understood when
      the structures of these substances are established.

PMID- 8159729
TI  - The insect tracheal system: a conduit for the systemic spread of Autographa
      californica M nuclear polyhedrosis virus.
AB  - Baculoviruses establish systemic infections within susceptible insect hosts, even
      though host tissues are surrounded by basal laminae, extracellular matrices that
      exclude particles smaller than these viruses. Using a recombinant Autographa
      californica M nuclear polyhedrosis virus containing a lacZ reporter gene under
      the control of a constitutive promoter, we followed the progression of infection
      in Trichoplusia ni larvae. We discovered that infection of the larval insect
      tracheal system (and not hemocytes, as thought previously) provides the major
      conduit for this virus to pass through basal laminae and to spread throughout the
      host. Tracheal epidermal cells, the only known cellular components of the
      tracheal system, share a common lymph system. Locally these cells contact one
      another by interdigitating cytoplasmic extensions called epidermal feet. These
      two features of the tracheal system are likely to facilitate the rapid systemic
      spread of the virus. The findings reported here have major implications for the
      fields of insect pathology and biological control and usher in an important
      consideration regarding host-range factors.

PMID- 8159730
TI  - Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory
      and nonulcerogenic.
AB  - We have examined the role of cyclooxygenase 2 (COX-2) in a model of inflammation
      in vivo. Carrageenan administration to the subcutaneous rat air pouch induces a
      rapid inflammatory response characterized by high levels of prostaglandins (PGs)
      and leukotrienes in the fluid exudate. The time course of the induction of COX-2
      mRNA and protein coincided with the production of PGs in the pouch tissue and
      cellular infiltrate. Carrageenan-induced COX-2 immunoreactivity was localized to
      macrophages obtained from the fluid exudate as well as to the inner surface layer
      of cells within the pouch lining. Dexamethasone inhibited both COX-2 expression
      and PG synthesis in the fluid exudate but failed to inhibit PG synthesis in the
      stomach. Furthermore, NS-398, a selective COX-2 inhibitor, and indomethacin, a
      nonselective COX-1/COX-2 inhibitor, blocked proinflammatory PG synthesis in the
      air pouch. In contrast, only indomethacin blocked gastric PG and, additionally,
      produced gastric lesions. These results suggest that inhibitors of COX-2 are
      potent antiinflammatory agents which do not produce the typical side effects
      (e.g., gastric ulcers) associated with the nonselective, COX-1-directed
      antiinflammatory drugs.

PMID- 8159731
TI  - Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer
      between diverged DNAs.
AB  - Bacterial mutS and mutL mutations confer large increases in recombination between
      sequences that are divergent by several percent at the nucleotide level, an
      effect attributed to a role for products of these genes in control of
      recombination fidelity. Since MutS and MutL are proteins involved in the earliest
      steps of mismatch repair, including mismatch recognition by MutS, we have tested
      the possibility that they may affect strand exchange in response to occurrence of
      mispairs within the recombination heteroduplex. We show that MutS abolishes RecA
      catalyzed strand transfer between fd and M13 bacteriophage DNAs, which vary by 3%
      at the nucleotide level, but is without effect on M13-M13 or fd-fd exchange.
      Although MutL alone has no effect on M13-fd heteroduplex formation, the protein
      dramatically enhances the inhibition of strand transfer mediated by MutS.
      Analysis of strand-transfer intermediates that accumulate in the presence of MutS
      and MutL indicates that the proteins block branch migration, presumably in
      response to occurrence of mispairs within newly formed heteroduplex.

PMID- 8159732
TI  - Proglucagon is processed to glucagon by prohormone convertase PC2 in alpha TC1-6
      cells.
AB  - Proglucagon is processed differentially in the pancreatic alpha cells and the
      intestinal L cells to yield either glucagon or glucagon-like peptide 1,
      respectively, structurally related hormones with opposing metabolic actions.
      Here, we have studied the processing of proglucagon in alpha TC1-6 cells, an
      islet-cell line transformed by simian virus 40 large tumor (T) antigen, a model
      of the pancreatic alpha cell. We found that these cells process proglucagon at
      certain dibasic cleavage sites to release glucagon and only small amounts of
      glucagon-like peptide 1, as demonstrated by both continuous and pulse-chase
      labeling experiments. Both normal islet alpha cells and alpha TC1-6 cells were
      shown to express the prohormone convertase PC2 at high levels, but not the
      related protease PC3. Expression of PC2 antisense RNA in alpha TC1-6 cells
      inhibited both PC2 production and proglucagon processing concomitantly. We
      conclude that PC2 is the key endoprotease responsible for proglucagon processing
      in cells with the alpha-cell phenotype.

PMID- 8159734
TI  - Community-level competition: asymmetrical dominance.
AB  - Ecological competition between entire communities of species occurs only when
      geographic barriers are suddenly removed. Recent empirical analysis suggests
      that, following the disappearance of a barrier, one community may swamp a second
      community, causing most or all of its species to go extinct. I provide
      theoretical insight into this result by showing that two "naive" competition
      communities mix randomly following the removal of a barrier. However, if the two
      communities have been "assembled," or self-organized, through a history of
      competitive exclusion, the communities are likely to battle as coordinated
      armies, with one or the other side ultimately claiming the entire landscape.

PMID- 8159733
TI  - Neurotrophin 3 stimulates the differentiation of motoneurons from avian neural
      tube progenitor cells.
AB  - Neurotrophin 3 (NT-3) promotes differentiation of neural tube progenitors into
      motoneurons expressing the BEN/SC1 and islet-1 epitopes. A 1.75- to 6.7-fold
      increase in BEN-positive motoneurons was obtained when quail neural tube cells
      were cultured with NT-3 at 0.1-10 ng/ml, respectively. In contrast, the overall
      number of cells, as well as the proportion of motoneurons that developed from
      cycling precursors, did not change. Addition of NT-3 at 1 ng/ml to cells obtained
      from ventral half-neural tubes promoted a 2.5-fold stimulation in motoneuron
      number, confirming the specificity of the effect. Moreover, NT-3 had no
      significant effect on survival of differentiated avian motoneurons. The
      distribution of trkC mRNA, which encodes the high-affinity receptor for NT-3, is
      consistent with these findings. trkC expression is homogeneous in the embryonic
      day 2 (E2) neural tube, becomes restricted to the mantle layer on E3, where
      differentiation occurs, and disappears from the ventral third of the E4-E5 spinal
      cord right before the onset of normal motoneuron death. These results suggest
      that NT-3 and trkC regulate early neurogenesis in the avian central nervous
      system.

PMID- 8159736
TI  - Recognition of oxidatively damaged erythrocytes by a macrophage receptor with
      specificity for oxidized low density lipoprotein.
AB  - Macrophages specifically bind and internalize oxidatively modified low density
      lipoprotein (LDL) via the acetyl-LDL receptor and possibly one or more additional
      receptors jointly designated here as scavenger receptors. It is well accepted
      that these receptors are intimately involved in the formation of foam cells
      during atherogenesis. However, the normal physiological or pathophysiological
      role for these receptors has not been established. Oxidation of plasma membranes
      is a common accompaniment of cell damage and senescence. In particular, aged
      erythrocytes demonstrate peroxidation of their cell membrane lipids. In the
      present studies we show that oxidized human erythrocytes (treated with copper
      plus ascorbate or hydrogen peroxide) are bound and phagocytosed by mouse
      peritoneal macrophages in the absence of opsonizing antibodies. There was little
      or no binding of untreated erythrocytes. Oxidized LDL, but not acetylated or
      native LDL, inhibited this binding and uptake of oxidized erythrocytes.
      Inhibitors of scavenger receptor binding, including polyinosinic acid and
      fucoidin, also prevented binding of the oxidized red blood cells. We suggest that
      oxidative damage of erythrocytes results in the formation of lipid-protein
      conjugate(s) closely related to some of the conjugates found in oxidized LDL,
      making the oxidized erythrocyte a ligand for the macrophage scavenger receptors,
      apparently at a site distinct from that responsible for the binding of acetylated
      LDL. Oxidative modification of plasma membranes may represent a general mechanism
      that marks damaged cells for phagocytosis by macrophages.

PMID- 8159735
TI  - Evolution of translational elongation factor (EF) sequences: reliability of
      global phylogenies inferred from EF-1 alpha(Tu) and EF-2(G) proteins.
AB  - The EF-2 coding genes of the Archaea Pyrococcus woesei and Desulfurococcus
      mobilis were cloned and sequenced. Global phylogenies were inferred by
      alternative tree-making methods from available EF-2(G) sequence data and
      contrasted with phylogenies constructed from the more conserved but shorter EF-1
      alpha(Tu) sequences. Both the monophyly (sensu Hennig) of Archaea and their
      subdivision into the kingdoms Crenarchaeota and Euryarchaeota are consistently
      inferred by analysis of EF-2(G) sequences, usually at a high bootstrap confidence
      level. In contrast, EF-1 alpha(Tu) phylogenies tend to be inconsistent with one
      another and show low bootstrap confidence levels. While evolutionary distance and
      DNA maximum parsimony analyses of EF-1 alpha(Tu) sequences do show archaeal
      monophyly, protein parsimony and DNA maximum-likelihood analyses of these data do
      not. In no case, however, do any of the tree topologies inferred from EF-1
      alpha(Tu) sequence analyses receive significant bootstrap support.

PMID- 8159738
TI  - Cloning and expression of a human P2U nucleotide receptor, a target for cystic
      fibrosis pharmacotherapy.
AB  - The Cl- secretory pathway that is defective in cystic fibrosis (CF) can be
      bypassed by an alternative pathway for Cl- transport that is activated by
      extracellular nucleotides. Accordingly, the P2 receptor that mediates this effect
      is a therapeutic target for improving Cl- secretion in CF patients. In this
      paper, we report the sequence and functional expression of a cDNA cloned from
      human airway epithelial (CF/T43) cells that encodes a protein with properties of
      a P2U nucleotide receptor. With a retrovirus system, the human airway clone was
      stably expressed in 1321N1 astrocytoma cells, a human cell line unresponsive to
      extracellular nucleotides. Studies of inositol phosphate accumulation and
      intracellular Ca2+ mobilization induced by extracellular nucleotides in 1321N1
      cells expressing the receptor identified this clone as the target receptor in
      human airway epithelia. In addition, we independently isolated an identical cDNA
      from human colonic epithelial (HT-29) cells, indicating that this is the same P2U
      receptor that has been functionally identified in other human tissues. Expression
      of the human P2U receptor (HP2U) in 1321N1 cells revealed evidence for autocrine
      ATP release and stimulation of transduced receptors. Thus, HP2U expression in the
      1321N1 cell line will be useful for studying autocrine regulatory mechanisms and
      in screening of potential therapeutic drugs.

PMID- 8159737
TI  - A model for beta-amyloid aggregation and neurotoxicity based on free radical
      generation by the peptide: relevance to Alzheimer disease.
AB  - beta-Amyloid is a 39- to 43-amino-acid neurotoxic peptide that aggregates to form
      the core of Alzheimer disease-associated senile (amyloid) plaques. No
      satisfactory hypothesis has yet been proposed to explain the mechanism of beta
      amyloid aggregation and toxicity. We present mass spectrometric and electron
      paramagnetic resonance spin trapping evidence that beta-amyloid, in aqueous
      solution, fragments and generates free radical peptides. beta-Amyloid fragments,
      at concentrations that previously have been shown to be neurotoxic to cultured
      neurons, can inactivate oxidation-sensitive glutamine synthetase and creatine
      kinase enzymes. Also, salicylate hydroxylation assays indicate that reactive
      oxygen species are generated by the beta-amyloid-(25-35) fragment during cell
      free incubation. These results are formulated into a free radical-based unifying
      hypothesis for neurotoxicity of beta-amyloid and are discussed with reference to
      membrane molecular alterations in Alzheimer disease.

PMID- 8159740
TI  - Effect of increasing doses of angiotensin II infused into normal and hypertensive
      Wistar rats on low density lipoprotein and fibrinogen uptake by aortic walls.
AB  - The effect of 6 days' s.c. infusions of angiotensin II at increasing doses was
      determined on the uptake of rat or human low density lipoprotein (LDL) and of
      human fibrinogen by aorta in normal and spontaneously hypertensive rats. Rat or
      human LDL or human fibrinogen was injected i.v. 5 days after the start of
      infusion, and 24 hr later the radioactivity of aortic walls was determined. Body
      weight was almost constant in control rats and moderately decreased in a dose
      dependent way by angiotensin II. Diastolic blood pressure decreased slightly over
      6 days in control rats and increased transiently at the lowest dose of
      angiotensin II and progressively with two higher concentrations. All three
      angiotensin II concentrations significantly increased the uptake of rat and human
      LDL and of fibrinogen by aorta. The increase was dose related for rat LDL but not
      for human LDL or fibrinogen. In spontaneously hypertensive rats of the same age
      in which blood pressure was higher than in angiotensin II-infused rats, protein
      uptakes were not increased. The blood content of aortic walls was negligible and
      not altered by angiotensin II. Therefore, the uptake of atherogenic plasma
      proteins by rat aorta is increased by angiotensin II, but this effect may be
      independent of its pressor action.

PMID- 8159739
TI  - Allelic polymorphism of emm loci provides evidence for horizontal gene spread in
      group A streptococci.
AB  - Group A streptococci have a virulence regulon containing a single emm locus or
      two or three distinct and adjacent loci of structurally related emm family genes.
      The products of the emm gene cluster consist of fibrillar surface proteins, at
      least some of which are known to contain determinants of type specificity located
      in their NH2-terminal regions, lying distal to the cell surface. The emm genes
      can be categorized into four major subfamilies (SFs), based on structural
      differences within their 3' regions encoding the peptidoglycan-spanning domain.
      In this study, we investigate the polymorphism within the 5' region of SF-4 and
      SF-3 emm genes (which occupy the first and last emm positions of the gene
      cluster, respectively) in 22 strains representing different serotypes. Our
      findings indicate that unlike the centrally positioned SF-1 or SF-2 genes, SF-3
      and SF-4 genes each display only limited polymorphism in their 5' regions,
      suggesting that their gene products may not be major contributors to type
      specificity. Two forms of the SF-3 gene (SF3a, SF3b) and two forms of the SF-4
      gene (SF4a, SF4b) are found to exist in all four possible combinations (SF3aSF4a,
      SF3aSF4b, SF3bSF4a, SF3bSF4b), strongly suggesting that horizontal gene spread
      has contributed to the evolution of emm genes and to the generation of emm gene
      diversity in group A streptococci.

PMID- 8159741
TI  - Modulation of cardiac Na+ channels expressed in a mammalian cell line and in
      ventricular myocytes by protein kinase C.
AB  - Cardiac rH1 Na+ channel alpha subunits were expressed in cells of the Chinese
      hamster lung 1610 cell line by transfection, and a stable cell line expressing
      cardiac Na+ channels (SNa-rH1) was isolated. Mean Na+ currents of 2.2 +/- 1.0 nA
      were recorded, which corresponds to a cell surface density of approximately 1-2
      channels active at the peak of the Na+ current per micron2. The expressed cardiac
      Na+ current was tetrodotoxin resistant (Kd = 1.8 microM) and had voltage
      dependent properties similar to those of the Na+ current in neonatal ventricular
      myocytes. Activation of protein kinase C by 1-oleoyl-2-acetyl-sn-glycerol (OAG)
      (10 microM) decreased this current approximately 33% at a holding potential of 
      114 mV and 56% at -94 mV. This reduction in peak current was caused in part by an
      8- to 14-mV shift of steady-state inactivation in the hyperpolarized direction.
      Na+ channel activation was unchanged. Effects of OAG in SNa-rH1 cells and in
      neonatal rat cardiac myocytes were similar, except that the time course of
      inactivation was slowed either transiently or persistently when protein kinase C
      was activated in myocytes bathed in low-Ca2+ (1 microM) or Ca(2+)-free solution
      but was unaffected in SNa-rH1 cells. The effects of OAG on cardiac Na+ current
      were blocked in cells that had been previously microinjected with a peptide
      inhibitor of protein kinase C but not with a peptide inhibitor of cAMP-dependent
      protein kinase, indicating that protein kinase C is responsible for the effect of
      OAG. Single-channel recordings from SNa-rH1 cells showed that the probability of
      channel opening was reduced by OAG, but the conductance was unaffected. OAG did
      not induce the late Na+ channel openings observed with PKC modulation of neuronal
      and skeletal muscle Na+ channels. Thus, the substantial reduction in Na+ current
      at normal diastolic depolarizations with 10 microM OAG is due to failure of
      channel opening in response to depolarization. Such Na+ current reductions may
      have profound effects on cardiac cell excitability.

PMID- 8159742
TI  - Evidence for a Ca(2+)-gated ryanodine-sensitive Ca2+ release channel in visceral
      smooth muscle.
AB  - Although a role for the ryanodine receptor (RyR) in Ca2+ signaling in smooth
      muscle has been inferred, direct information on the biochemical and functional
      properties of the receptor has been largely lacking. Studies were thus carried
      out to purify and characterize the RyR in stomach smooth muscle cells from the
      toad Bufo marinus. Intracellular Ca2+ measurements with the Ca(2+)-sensitive
      fluorescent indicator fura-2 under voltage clamp indicated the presence of a
      caffeine- and ryanodine-sensitive internal store for Ca2+ in these cells. The
      (CHAPS)-solubilized, [3H]ryanodine-labeled RyR of toad smooth muscle was
      partially purified from microsomal membranes by rate density centrifugation as a
      30-S protein complex. SDS/PAGE indicated the comigration of a high molecular
      weight polypeptide with the peak attributed to 30-S RyR, which had a mobility
      similar to the cardiac RyR and on immunoblots cross-reacted with a monoclonal
      antibody to the canine cardiac RyR. Following planar lipid bilayer reconstitution
      of 30-S stomach muscle RyR fractions, single-channel currents (830 pS with 250 mM
      K+ as the permeant ion) were observed that were activated by Ca2+ and modified by
      ryanodine. In vesicle-45Ca2+ efflux measurements, the toad channel was activated
      to a greater extent at 100-1000 microM than 1-10 microM Ca2+. These results
      suggest that toad stomach muscle contains a ryanodine-sensitive Ca2+ release
      channel with properties similar but not identical to those of the mammalian
      skeletal and cardiac Ca(2+)-release channels.

PMID- 8159743
TI  - Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons.
AB  - The survival of developing motor neurons depends on factors secreted from
      skeletal muscles and from cells within the central nervous system. Although
      several members of the nerve growth factor protein family [neurotrophins (NTs)]
      are able to maintain developing rat motor neurons in vitro, only the brain
      derived neurotrophic factor has been shown to have significant effects on the
      survival of motor neurons in vivo. In the present study, we demonstrate that NT
      4/5 also prevents injury-induced death of facial motor neurons in neonatal rats.
      Furthermore, facial motor neurons express a functional receptor for NT-4/5,
      whereas mRNA-encoding NT-4/5 can be detected in their environment throughout
      embryonic and postnatal life. Thus, both NT-4/5 and brain-derived neurotrophic
      factor may be physiological survival factors for facial motor neurons and may
      serve as therapeutic agents for motor neuron disease.

PMID- 8159744
TI  - Neonatal motoneurons overexpressing the bcl-2 protooncogene in transgenic mice
      are protected from axotomy-induced cell death.
AB  - In vitro, the overexpression of the bcl-2 protooncogene in cultured neurons has
      been shown to prevent apoptosis induced by neurotrophic factor deprivation. We
      have generated transgenic mice overexpressing the Bcl-2 protein in neurons,
      including motoneurons of the facial nucleus. We have tested whether Bcl-2 could
      protect these motoneurons from experimentally induced cell death in new born
      mice. To address this question, we performed unilateral lesion of the facial
      nerve of wild-type and transgenic 2-day-old mice. In wild-type mice, the lesioned
      nerve and the corresponding motoneuron cell bodies in the facial nucleus
      underwent rapid degeneration. In contrast, in transgenic mice, facial motoneurons
      survived axotomy. Not only their cell bodies but also their axons were protected
      up to the lesion site. These results demonstrate that in vivo Bcl-2 protects
      neonatal motoneurons from degeneration after axonal injury. A better
      understanding of the mechanisms by which Bcl-2 prevents neuronal cell death in
      vivo could lead to the development of strategies for the treatment of motoneuron
      degenerative diseases.

PMID- 8159745
TI  - Portion-mixing peptide libraries of quenched fluorogenic substrates for complete
      subsite mapping of endoprotease specificity.
AB  - A solid-phase assay for the complete subsite mapping of the active site of
      endoproteases has been developed. A library of resin-bound protease substrates
      was synthesized both on kieselguhr-supported polyamide resin and on a
      polyethylene glycol-poly-(N,N-dimethylacrylamide) copolymer type of resin that
      allows proteases to diffuse into the interior and perform their catalytic
      activity. Anthranilic acid and 3-nitrotyrosine were used as an efficient donor
      acceptor pair for the resonance energy transfer. The synthesis was performed in a
      manual library generator that allows simple wet mixing of the beads and parallel
      washing procedures. After treatment with subtilisin Carlsberg, fluorescing beads
      were collected and subjected to peptide sequencing, affording the preferred
      sequences, their cleavage bond, and a semiquantitative estimation of the
      turnover. A statistical distribution of preferred amino acids was obtained for
      each subsite. The result was compared with data from kinetic studies in solution.

PMID- 8159746
TI  - PP1 gamma 2, a testis-specific protein-serine/threonine-phosphatase type 1
      catalytic subunit, is associated with a protein having high sequence homology
      with the 78-kDa glucose-regulated protein, a member of the 70-kDa heat shock
      protein family.
AB  - Protein phosphatase 1 gamma 2 (PP1 gamma 2) is a testis-specific isotype of the
      protein-serine/threonine-phosphatase type 1 catalytic subunit. Three native forms
      of PP1 gamma 2 were detected in a crude fraction of rat testis by electrophoresis
      in a nondenaturing polyacrylamide gel. We purified a major native form of PP1
      gamma 2 to homogeneity by successive column chromatography on Mono Q-Sepharose,
      EAH-agarose, protamine-agarose, and G3000SW and by electrophoresis in a
      nondenaturing polyacrylamide gel. The G3000SW-purified PP1 gamma 2 native form
      had an apparent molecular mass of 170 kDa. The purified holoenzyme from
      nondenaturing polyacrylamide gel was composed of the catalytic subunit and two
      noncatalytic subunits, of 78 kDa and 55 kDa. Partial amino acid sequence analysis
      of the 78-kDa protein suggested that it is the 78-kDa glucose-regulated protein,
      a member of the 70-kDa heat shock protein family. The 78-kDa protein may possibly
      function as a chaperone or by confining substrate specificity of PP1 gamma 2.

PMID- 8159747
TI  - Pseudouridine formation in U2 small nuclear RNA.
AB  - U2 small nuclear RNA contains 13 pseudouridine (psi) nucleotides, of which 11 are
      clustered in 5' regions involved in base-pairing interactions with other RNAs in
      the spliceosome. As a first step toward understanding the psi formation pathway
      in U2 RNA, we investigated psi formation on unmodified human U2 RNA in a HeLa
      cell extract system. Psi formation was found to occur specifically within only
      those RNase T1 oligonucleotide fragments of U2 RNA known to contain psi in vivo.
      Using 5-fluorouridine (FUrd)-containing U2 RNAs as specific inhibitors of psi
      formation in non-FUrd-substituted substrate U2 RNA, we found that wild-type FUrd
      containing U2 RNA as well as several FUrd-containing mutant U2 RNAs completely
      inhibited psi formation. In contrast, certain other mutant U2 RNAs containing
      FUrd displayed reduced inhibitory capacity. In these cases psi modifications
      occurred in specific RNase T1 fragments of the substrate U2 RNA only if the FUrd
      containing competitor RNA was mutated at or near this site. Formation of psi at
      one site in U2 RNA appeared to be neither dependent on prior psi formation at
      another site or sites nor required for subsequent psi formation elsewhere in the
      molecule. This autonomous mode of psi formation may be driven by multiple psi
      synthase enzymes acting independently at different sites in U2 RNA.

PMID- 8159749
TI  - A discrete Fourier analysis for evolutionary trees.
AB  - Discrete Fourier transformations have recently been developed to model the
      evolution of two-state characters (the Cavender/Farris model). We report here the
      extension of these transformations to provide invertible relationships between a
      phylogenetic tree T (with three probability parameters of nucleotide substitution
      on each edge corresponding to Kimura's 3ST model) and the expected frequencies of
      the nucleotide patterns in the sequences. We refer to these relationships as
      spectral analysis. In either model with independent and identically distributed
      site substitutions, spectral analysis allows a global correction for all multiple
      substitutions (second- and higher-order interactions), independent of any
      particular tree. From these corrected data we use a least-squares selection
      procedure, the closest tree algorithm, to infer an evolutionary tree. Other
      selection criteria such as parsimony or compatibility analysis could also be
      used; each of these criteria will be statistically consistent for these models.
      The closest tree algorithm selects a unique best-fit phylogenetic tree together
      with independent edge length parameters for each edge. The method is illustrated
      with an analysis of some primate hemoglobin sequences.

PMID- 8159748
TI  - Drosophila syndecan: conservation of a cell-surface heparan sulfate proteoglycan.
AB  - In mammals, cell-surface heparan sulfate is required for the action of basic
      fibroblast growth factor, fibronectin, antithrombin III, as well as other
      effectors. The syndecans, a gene family of four transmembrane proteoglycans that
      participates in these interactions, are the major source of this heparan sulfate.
      Based on the conserved transmembrane and cytoplasmic domains of the mammalian
      syndecans, a single syndecan-like gene was detected and localized in the
      Drosophila genome. As in mammals, Drosophila syndecan is a heparan sulfate
      proteoglycan expressed at the cell surface that can be shed from cultured cells.
      The single Drosophila syndecan is expressed in embryonic tissues that correspond
      with those tissues in mammals that express distinct members of the syndecan
      family predominantly. Conservation of this class of molecules suggests that
      Drosophila, like mammals, uses cell-surface heparan sulfate as a receptor or
      coreceptor for extracellular effector molecules.

PMID- 8159750
TI  - Cooperative interactions between the interleukin 2 receptor alpha and beta chains
      alter the interleukin 2-binding affinity of the receptor subunits.
AB  - The interleukin 2 (IL-2) receptor (IL-2R) is a multisubunit receptor that
      includes three major IL-2 binding subunits, the IL-2R alpha, beta, and gamma
      chains. We have detected and analyzed cooperative interactions between the IL-2R
      alpha and beta chains (IL-2R alpha and IL-2R beta, respectively) in COS cells
      transfected with cDNAs encoding the IL-2R alpha, the IL-2R beta, or both cDNAs.
      We demonstrated that IL-2 F42A, an analog that fails to bind to the isolated IL
      2R alpha subunit and would be predicted by the hierarchical affinity-conversion
      model to have impaired binding to cells expressing both chains, instead readily
      binds to the IL-2R alpha/beta heterodimer in COS cells. Furthermore, this binding
      is abolished by the antibody HIEI that separates the two IL-2R subunits. The
      monoclonal antibodies anti-Tac and Mik-beta 1 directed at the IL-2-binding sites
      on IL-2R alpha and IL-2R beta, respectively, block ligand binding to the
      heterodimer. This binding pattern is inconsistent with the strict hierarchical
      affinity-conversion model that mandates an initial binding of IL-2 to IL-2R alpha
      followed by binding of the IL-2/IL-2R alpha complex to IL-2R beta. Instead, our
      results support an alternative model of preformed complexes of IL-2R beta with
      other IL-2R subunits. In this alternative model, IL-2R alpha and -beta exist in
      part as preformed complexes in which the affinity of IL-2R beta for IL-2 is
      altered by the proximity of IL-2R alpha, through mechanisms that do not require
      the prior binding of IL-2 to IL-2R alpha.

PMID- 8159751
TI  - Molecular cloning, expression, and partial characterization of a second human
      tissue-factor-pathway inhibitor.
AB  - Previous studies have shown that tissue-factor-pathway inhibitor (TFPI) is an
      important regulator of the extrinsic pathway of blood coagulation through its
      ability to inhibit factor Xa and factor VIIa-tissue factor activity. We describe
      the molecular cloning and expression of a full-length cDNA that encodes a
      molecule, designated TFPI-2, that has a similar overall domain organization and
      considerable primary amino acid sequence homology to TFPI. After a 22-residue
      signal peptide, the mature protein contains 213 amino acids with 18 cysteines and
      two canonical N-linked glycosylation sites. The deduced sequence of mature TFPI-2
      revealed a short acidic amino-terminal region, three tandem Kunitz-type domains,
      and a carboxyl-terminal tail highly enriched in basic amino acids. Northern
      analysis indicates that TFPI-2 is transcribed in umbilical vein endothelial
      cells, liver, and placenta. TFPI-2 was expressed in baby hamster kidney cells and
      purified from the serum-free conditioned medium by a combination of heparin
      agarose chromatography, Mono Q FPLC, Mono S FPLC, and Superose 12 FPLC. Purified
      TFPI-2 migrated as a single band in SDS/PAGE and exhibited a molecular mass of 32
      kDa in the presence and absence of reducing agent. The amino-terminal sequence of
      recombinant TFPI-2 was identical to that predicted from the cDNA. Despite its
      structural similarity to TFPI, the purified recombinant TFPI-2 failed to react
      with polyclonal anti-TFPI IgG. Preliminary studies indicated that purified
      recombinant TFPI-2 strongly inhibited the amidolytic activities of trypsin and
      the factor VIIa-tissue factor complex. In addition, the inhibition of factor VIIa
      tissue factor amidolytic activity by recombinant TFPI-2 was markedly enhanced in
      the presence of heparin. TFPI-2 at high concentrations weakly inhibited the
      amidolytic activity of human factor Xa, but had no measurable effect on the
      amidolytic activity of human thrombin.

PMID- 8159752
TI  - A beta-lactone related to lactacystin induces neurite outgrowth in a
      neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma
      cell line.
AB  - Lactacystin, a microbial natural product, induces neurite outgrowth in Neuro 2A
      mouse neuroblastoma cells and inhibits progression of synchronized Neuro 2A cells
      and MG-63 human osteosarcoma cells beyond the G1 phase of the cell cycle. A
      related beta-lactone, clasto-lactacystin beta-lactone, formally the product of
      elimination of N-acetylcysteine from lactacystin, is also active, whereas the
      corresponding clastolactacystin dihydroxy acid is completely inactive. Structural
      analogs of lactacystin altered only in the N-acetylcysteine moiety are active,
      while structural or stereochemical modifications of the gamma-lactam ring or the
      hydroxyisobutyl group lead to partial or complete loss of activity. The inactive
      compounds do not antagonize the effects of lactacystin in either neurite
      outgrowth or cell cycle progression assays. The response to lactacystin involves
      induction of a predominantly bipolar morphology that is maximal 16-32 h after
      treatment and is distinct from the response to several other treatments that
      result in morphological differentiation. Neurite outgrowth in response to
      lactacystin appears to be dependent upon microtubule assembly, actin
      polymerization, and de novo protein synthesis. The observed structure-activity
      relationships suggest that lactacystin and its related beta-lactone may act via
      acylation of one or more relevant target molecule(s) in the cell.

PMID- 8159753
TI  - Distinct DNA-binding properties of the high mobility group domain of murine and
      human SRY sex-determining factors.
AB  - The mammalian sex-determining gene SRY (sex-determining region on Y chromosome)
      encodes a member of the high mobility group (HMG) family of regulatory proteins.
      The HMG domain of the SRY protein represents a DNA binding motif that displays
      rather unusually weak evolutionary conservation of amino acids between human and
      mouse sequences. Together with the previous finding that the human (h) SRY gene
      is unable to induce a male phenotype in genetically female transgenic mice, these
      observations raise questions concerning the DNA binding properties of SRY
      proteins. Here, we present data that indicate that the DNA binding and bending
      properties of the HMG domains of murine (m) SRY and hSRY differ from each other.
      In comparison, mSRY shows more-extensive major-groove contacts with DNA and a
      higher specificity of sequence recognition than hSRY. Moreover, the extent of
      protein-induced DNA bending differs from the HMG domains of hSRY and mSRY. These
      differences in DNA binding by hSRY and mSRY may, in part, account for the
      functional differences observed with these gene products.

PMID- 8159754
TI  - Kinetics of an RNA conformational switch.
AB  - The spliced leader RNA from Leptomonas collosoma has two competing secondary
      structures of nearly equal free energy. Short, complementary oligonucleotides can
      drive the structure from one form of the other. We report stopped-flow rapid
      mixing and temperature-jump measurements of the kinetics of the structural
      switch. At high concentrations of oligonucleotide, the rate of binding becomes
      limited by the rate of the structural switch, which occurs on a time scale of a
      fraction of a second. The low activation energy observed for the process implies
      a branch migration type of mechanism in which portions of the two competing
      helices transiently coexist.

PMID- 8159756
TI  - A tumor suppressor locus within 3p14-p12 mediates rapid cell death of renal cell
      carcinoma in vivo.
AB  - High frequency loss of alleles and cytogenetic aberrations on the short arm of
      chromosome 3 have been documented in renal cell carcinoma (RCC). Potentially,
      three distinct regions on 3p could encode tumor suppressor genes involved in the
      genesis of this cancer. We report that the introduction of a centric fragment of
      3p, encompassing 3p14-q11, into a highly malignant RCC cell line resulted in a
      dramatic suppression of tumor growth in athymic nude mice. Another defined
      deletion hybrid contained the region 3p12-q24 of the introduced human chromosome
      and failed to suppress tumorigenicity. These data functionally define a tumor
      suppressor locus, nonpapillary renal carcinoma-1 (NRC-1), within 3p14-p12, the
      most proximal region of high frequency allele loss in sporadic RCC as well as the
      region containing the translocation breakpoint in familial RCC. Furthermore, we
      provide functional evidence that NRC-1 controls the growth of RCC cells by
      inducing rapid cell death in vivo.

PMID- 8159755
TI  - Truncation mutants define and locate cytoplasmic barriers to lateral mobility of
      membrane glycoproteins.
AB  - The lateral mobility of cell membrane glycoproteins is often restricted by
      dynamic barriers. These barriers have been detected by measurements of
      fluorescence photobleaching and recovery (FPR) and barrier-free path (BFP). To
      define the location and properties of the barriers, we compared the lateral
      mobility, measured by FPR and BFP, of wild-type class I major histocompatibility
      complex (MHC) membrane glycoproteins with the lateral mobility of mutant class I
      MHC glycoproteins truncated in their cytoplasmic domains. Mutants with 0 or 4
      residues in the cytoplasmic domain were as mobile as lipid-anchored class I MHC
      molecules, molecules whose lateral mobility is relatively unrestricted by
      barriers. In contrast, mobility of class I MHC molecules with 7-residue
      cytoplasmic domains was as restricted as mobility of class I molecules with full
      length, 31-residue cytoplasmic domains. Though some of the difference between the
      mobilities of mutants with 4- or 0-residue domains and the other class I
      molecules may be due to differences in the net charge of the cytoplasmic domain,
      FPR measurements of the mobility of molecules with 7-residue domains show that
      length of the cytoplasmic domain has an important influence on the lateral
      mobility. Model calculations suggest that the barriers to lateral mobility are 2
      3 nm below the membrane bilayer.

PMID- 8159757
TI  - Three-dimensional spectral-spatial EPR imaging of free radicals in the heart: a
      technique for imaging tissue metabolism and oxygenation.
AB  - It has been hypothesized that free radical metabolism and oxygenation in living
      organs and tissues such as the heart may vary over the spatially defined tissue
      structure. In an effort to study these spatially defined differences, we have
      developed electron paramagnetic resonance imaging instrumentation enabling the
      performance of three-dimensional spectral-spatial images of free radicals infused
      into the heart and large vessels. Using this instrumentation, high-quality three
      dimensional spectral-spatial images of isolated perfused rat hearts and rabbit
      aortas are obtained. In the isolated aorta, it is shown that spatially and
      spectrally accurate images of the vessel lumen and wall could be obtained in this
      living vascular tissue. In the isolated rat heart, imaging experiments were
      performed to determine the kinetics of radical clearance at different spatial
      locations within the heart during myocardial ischemia. The kinetic data show the
      existence of regional and transmural differences in myocardial free radical
      clearance. It is further demonstrated that EPR imaging can be used to
      noninvasively measure spatially localized oxygen concentrations in the heart.
      Thus, the technique of spectral-spatial EPR imaging is shown to be a powerful
      tool in providing spatial information regarding the free radical distribution,
      metabolism, and tissue oxygenation in living biological organs and tissues.

PMID- 8159758
TI  - Cytotoxicity of immunoglobulins from amyotrophic lateral sclerosis patients on a
      hybrid motoneuron cell line.
AB  - Patients with amyotrophic lateral sclerosis possess antibodies (ALS IgGs) that
      bind to L-type skeletal muscle voltage-gated calcium channels (VGCCs) and inhibit
      L-type calcium current. To determine whether interaction of ALS IgGs with
      neuronal VGCCs might influence motoneuron survival, we used a motoneuron
      neuroblastoma hybrid (VSC 4.1) cell line expressing binding sites for inhibitors
      of L-, N-, and P-type VGCCs. Using direct viable cell counts, quantitation of
      propidium iodide- and fluorescein diacetate-labeled cells, and lactate
      dehydrogenase release to assess cell survival, we document that ALS IgG kills 40
      70% of cAMP-differentiated VSC 4.1 cells within 2 days. ALS IgG-mediated
      cytotoxicity is dependent on extracellular calcium and is prevented by peptide
      antagonists of N- or P-type VGCCs but not by dihydropyridine modulators of L-type
      VGCCs. Preincubating IgG with purified intact L-type VGCC or with isolated VGCC
      alpha 1 subunit also blocks ALS IgG-mediated cytotoxicity. These results suggest
      that ALS IgG may directly lead to motoneuron cell death by a mechanism requiring
      extracellular calcium and mediated by neuronal-type calcium channels.

PMID- 8159759
TI  - Reconstitution of a yeast protein kinase cascade in vitro: activation of the
      yeast MEK homologue STE7 by STE11.
AB  - The mating-factor response pathway of Saccharomyces cerevisiae employs a set of
      protein kinase similar to kinases that function in signal transduction pathways
      of metazoans. We have purified the yeast protein kinases encoded by STE11, STE7,
      and FUS3 as fusions to glutathione S-transferase (GST) and reconstituted a kinase
      cascade in which STE11 phosphorylates and activates STE7, which in turn
      phosphorylates the mitogen-activated protein kinase FUS3. GST-STE11 is active
      even when purified from cells that have not been treated with alpha-factor. This
      observation raises the possibility that STE11 activity is governed by an
      inhibitor which is regulated by pheromone. We also identify a STE11-dependent
      phosphorylation site in STE7 which is required for activity of STE7. Conservation
      of this site in the mammalian STE7 homologue MEK and other STE7 relatives
      suggests that this may be a regulatory phosphorylation site in all MAP kinase
      kinases.

PMID- 8159760
TI  - Purification and initial characterization of a potential plant vacuolar targeting
      receptor.
AB  - Clathrin-coated vesicles are known to be involved in the transport of proteins
      from the Golgi to the vacuole in plant cells. The mechanisms by which proteins
      are directed into this pathway are not known. Here we identify an integral
      membrane protein of approximately 80 kDa, extracted from clathrin-coated vesicles
      of developing pea (Pisum sativum L.) cotyledons, that bound at neutral pH to an
      affinity column prepared with the N-terminal targeting determinant of the
      vacuolar thiol protease, proaleurain, and eluted when the pH was lowered to 4.
      The protein was not retained on a control column prepared with the N-terminal
      sequence of a homologous, secreted thiol protease, endopeptidase B. The 80-kDa
      protein also accumulated in a membrane fraction that is less dense than clathrin
      coated vesicles. In vitro studies demonstrated a binding constant of 37 nM
      between the approximately 80 kDa protein and the proaleurain targeting
      determinant. A peptide with a vacuolar targeting determinant from prosporamin
      weakly competed for binding to the approximately-80 kDa protein, while a peptide
      carrying a single amino acid substitution known to abolish prosporamin vacuolar
      targeting had no measurable binding affinity for the protein. The binding protein
      is a glycoprotein with a transmembrane orientation in which the C terminus is
      exposed to the cytoplasm. The binding domain is located in the N-terminal luminal
      portion of the protein. These properties of the binding protein are consistent
      with the function of a receptor that would select proteins in the trans-Golgi for
      sorting to clathrin-coated vesicles and delivery to the vacuole.

PMID- 8159761
TI  - Mariner-like elements in hymenopteran species: insertion site and distribution.
AB  - Copies of mariner-like element (MLE) transposons in two species, the bumble bee,
      Bombus terrestris, and the ant, Myrmica ruginodis, were sequenced. The full-sized
      elements are 1250 bp long in both species and include 28-bp inverted terminal
      repeats. The five copies sequenced were approximately 75% similar to a mariner
      element (peach) of Drosophila mauritiana. The distribution of MLE in 27
      hymenopteran species was studied by PCR and Southern blot hybridization; 93% of
      the species contained one or more of the four major forms of the element. They
      are inserted in their host genomes, in the middle of a degenerated 30-bp
      palindrome, which is itself located in an 85-bp conserved region with a purine
      rich tail at one of its ends. The hymenopteran MLEs lie in a specific insertion
      site, suggesting that this region is conserved. It is thus possible that this
      region may be a selectively neutral insertion site, which would explain why these
      elements are widespread in hymenopteran genomes and are not eliminated by male
      haploidy.

PMID- 8159762
TI  - Initiation preference at a yeast origin of replication.
AB  - Replication origins in the yeast Saccharomyces cerevisiae are identified as
      autonomous replication sequence (ARS) elements. To examine the effect of origin
      density on replication initiation, we have analyzed the replication of a plasmid
      that contains two copies of the same origin, ARS1. The activation of origins and
      the direction that replication forks move through flanking sequences can be
      physically determined by analyzing replication intermediates on two-dimensional
      agarose gels. We find that only one of the two identical ARSs on the plasmid
      initiates replication on any given plasmid molecule; that is, this close spacing
      of ARSs results in an apparent interference between the potential origins.
      Moreover, in the particular plasmid that we constructed, one of the two identical
      copies of ARS1 is used four times more frequently than the other one. These
      results show that the plasmid context is critical for determining the preferred
      origin. This origin preference is also exhibited when the tandem copies of ARS1
      are introduced into a yeast chromosome. The sequences responsible for
      establishing the origin preference have been identified by deletion analysis and
      are found to reside in a portion of the yeast URA3 gene.

PMID- 8159763
TI  - Clonal variants of hybridoma cells that switch isotype at a high frequency.
AB  - As B cells differentiate under the influence of antigen and T cells, they
      frequently switch from the expression of IgM antibody to the expression of other
      isotypes. This is accomplished by rearranging the expressed variable region gene
      to downstream constant region genes and deleting the intervening sequences. Some
      B-cell lines that represent early stages in development switch constitutively in
      culture at frequencies that approach those of lipopolysaccharide- or lymphokine
      stimulated normal B cells. Hybridoma cells represent a later stage of development
      and rarely switch in culture. In contrast to early B-cell lines, hybridomas
      produce large amounts of immunoglobulin, and single cells can be assayed easily
      for the expression of new isotypes. We have used the ELISA spot assay and
      fluctuation analysis to determine the rate of switching of two hybridoma cell
      lines. By identifying subclones that switched more frequently, we have
      progressively enriched for cells that switch spontaneously at higher rates. These
      cells, like normal cells, switch by rearrangement and deletion, and the frequency
      of switched cells in some of the clones is comparable to that which has been
      observed in less differentiated B-cell lines and in normal B cells.

PMID- 8159764
TI  - Seroepidemiology of water-borne hepatitis in India and evidence for a third
      enterically-transmitted hepatitis agent.
AB  - Many epidemics of water-borne hepatitis have occurred throughout India. These
      were thought to be epidemics of hepatitis A until 1980, when evidence for an
      enterically transmitted non-A, non-B hepatitis was first reported. Subsequently,
      hepatitis E virus was discovered and most recent epidemics of enterically
      transmitted non-A, non-B hepatitis have been attributed to hepatitis E virus
      infection. However, only a limited number of cases have been confirmed by immuno
      electron microscopy, polymerase chain reaction, or seroconversion. In the present
      study we have performed a retrospective seroepidemiologic study of 17 epidemics
      of water-borne hepatitis in India. We have confirmed that 16 of the 17 epidemics
      were caused at least in part by serologically closely related hepatitis E
      viruses. However, one epidemic, in the Andaman Islands, and possibly a
      significant minority of cases in other epidemics, appears to have been caused by
      a previously unrecognized hepatitis agent.

PMID- 8159765
TI  - Borrelia burgdorferi swims with a planar waveform similar to that of eukaryotic
      flagella.
AB  - Borrelia burgdorferi is a motile spirochete with multiple internal periplasmic
      flagella (PFs) attached near each end of the cell cylinder; these PFs overlap in
      the cell center. We analyzed the shape and motion of wild type and PF-deficient
      mutants using both photomicrography and video microscopy. We found that swimming
      cells resembled the dynamic movements of eukaryotic flagella. In contrast to
      helically shaped spirochetes, which propagate spiral waves, translating B.
      burgdorferi swam with a planar waveform with occasional axial twists; waves had a
      peak-to-peak amplitude of 0.85 micron and a wavelength of 3.19 microns. Planar
      waves began full-sized at the anterior end and propagated toward the back end of
      the cell. Concomitantly, these waves gyrated counter-clockwise as viewed from the
      posterior end along the cell axis. In nontranslating cells, wave propagation
      ceased. Either the waveform of nontranslating cells resembled the translating
      form, or the cells became markedly contorted. Cells of the PF-deficient mutant
      isolated by Sadziene et al. [Sadziene, A., Thomas, D. D., Bundoc, V. G., Holt, S.
      C. & Barbour, A. G. (1991) J. Clin. Invest. 88, 82-92] were found to be
      relatively straight. The results suggest that the shape of B. burgdorferi is
      dictated by interactions between the cell body and the PFs. In addition, the PFs
      from opposite ends of the cell are believed to interact with one another so that
      during the markedly distorted nontranslational form, the PFs from opposite ends
      rotate in opposing directions around one another, causing the cell to bend.

PMID- 8159766
TI  - A family of potassium channel genes related to eag in Drosophila and mammals.
AB  - We have identified a conserved family of genes related to Drosophila eag, which
      encodes a distinct type of voltage-activated K+ channel. Three related genes were
      recovered in screens of cDNA libraries from Drosophila, mouse, and human tissues.
      One gene is the mouse counterpart of eag; the other two represent additional
      subfamilies. The human gene maps to chromosome 7. Family members share at least
      47% amino acid identity in their hydrophobic cores and all contain a segment
      homologous to a cyclic nucleotide-binding domain. Sequence comparisons indicate
      that members of this family are most closely related to vertebrate cyclic
      nucleotide-gated cation channels and plant inward-rectifying K+ channels. The
      existence of another family of K+ channel structural genes further extends the
      known diversity of K+ channels and has important implications for the structure,
      function, and evolution of the superfamily of voltage-sensitive ion channels.

PMID- 8159767
TI  - SPARC (secreted protein acidic and rich in cysteine) regulates endothelial cell
      shape and barrier function.
AB  - SPARC (secreted protein acidic and rich in cysteine) can be selectively expressed
      by the endothelium in response to certain types of injury and induces rounding in
      adherent endothelial cells in vitro. To determine whether SPARC might influence
      endothelial permeability, we studied the effect of exogenous SPARC on the
      movement of 14C-labeled bovine serum albumin across postconfluent bovine
      pulmonary artery endothelial cells. SPARC increased (P < 0.02) transendothelial
      albumin flux in a dose-dependent manner at concentrations > or = 0.5
      microgram/ml. At a fixed dose (15 micrograms/ml), exposure times > or = 1 h
      augmented (P < 0.005) albumin flux by 1.3- to 3.6-fold; this increase was blocked
      by anti-SPARC antibodies but not by inhibition of protein synthesis. Barrier
      dysfunction was not associated with loss of cell viability. Monolayers exposed to
      SPARC exhibited a rounded morphology and intercellular gaps. Prior stabilization
      of F-actin with phallicidin protected against the changes in barrier function (P
      = 0.0001) that were otherwise induced by SPARC. Bovine aortic and retinal
      microvascular endothelia also responded to SPARC. We propose that SPARC regulates
      endothelial barrier function through F-actin-dependent changes in cell shape,
      coincident with the appearance of intercellular gaps, that provide a paracellular
      pathway for extravasation of macromolecules.

PMID- 8159768
TI  - A conserved sequence motif within the exceptionally diverse telomeric sequences
      of budding yeasts.
AB  - Telomeric DNA sequences have generally been found to be remarkably conserved in
      evolution, typically consisting of repeated, very short sequence units containing
      clusters of G residues. Recently however the telomeric DNA of the asexual yeast
      Candida albicans was shown to consist of much longer repeat units. Here we report
      the identification of seven additional telomeric sequences from sexual and
      asexual budding yeast species. The telomeric repeat units from this group of
      relatively closely related species show more phylogenetic diversity in length (8
      25 bp), sequence, and composition than has been seen previously throughout a wide
      phylogenetic range of other eukaryotes. We also show that certain strains of the
      asexual diploid species Candida tropicalis have two forms of telomeric repeats,
      which appear to differ by a single base pair. Despite their great diversity, the
      telomeric repeat units of C. albicans, Saccharomyces cerevisiae, and all of the
      species we have examined in this report share a conserved approximately 6-bp
      motif of T and G residues resembling more typical telomeric sequences.

PMID- 8159769
TI  - The murine c-fgr gene product associated with Ly6C and p70 integral membrane
      protein is expressed in cells of a monocyte/macrophage lineage.
AB  - The c-fgr gene is a member of the Src family of protooncogene tyrosine kinases. A
      monoclonal antibody (2H2) that recognizes the specific region of the N-terminal
      domain of the murine c-fgr gene product (Fgr) has been established. With an
      immune complex kinase assay in a monocytic leukemia cell line, 2H2 monoclonal
      antibody was shown to precipitate a 59-kDa protein that corresponds in molecular
      mass to murine Fgr. Fgr was expressed highly in lymph nodes, slightly in spleen
      and peripheral blood leukocytes, and barely in the thymus and was not detected in
      bone marrow. In the presence of a mild detergent, Fgr was coimmunoprecipitated
      with a 70-kDa protein (p70) or with p70 plus several other molecules that were
      expressed on the cell-surface membrane of macrophage tumor cell lines PU5-1.8 and
      J774.1, respectively. By contrast, Fgr was not coimmunoprecipitated with a low
      affinity receptor for the Fc portion of IgG that is associated with human Fgr.
      The molecule was also coimmunoprecipitated with the Ly6C molecule from a
      macrophage cell line (J774.1) that showed protein-tyrosine kinase activity.
      Peptide mapping revealed that this kinase activity was derived from Fgr. The
      similarity of relationship between this intramembrane p70 and/or Ly6C and
      cytoplasmic Fgr to relationships previously reported between T-cell antigen
      receptor complex, including CD4 and CD8 coreceptors, and Lck or Fyn in T cells
      and between surface IgM and Lyn or Blk in B cells, suggests that the Fgr and p70
      or Ly6C are, indeed, associated with each other and in the murine system may be
      responsible for recognition of extracellular substances (either cellular or
      noncellular) and for signal transduction in cells of monocyte/macrophage lineage.

PMID- 8159771
TI  - Posttranscriptional modification of myosin heavy-chain gene expression in the
      hypertrophied rat myocardium.
AB  - Hypertrophy of the myocardium in response to pressure or volume overload elicits
      a change in myofibrillar protein content as a result of changes in both
      transcriptional and translational regulation of gene expression. Hemodynamic
      overload caused by aortic constriction produced changes in the expression of the
      two isoforms of myosin heavy chain (MHC) with a 319% increase in beta-MHC mRNA
      and a 54% decrease in alpha-MHC mRNA (P < 0.01). Cardiac unloading as a result of
      heterotopic transplantation resulted in a decrease in cardiac mass and a similar
      shift in MHC isoform expression. In this study. We investigated cardiac gene
      transcription to understand how different hemodynamic stimuli produce similar
      cardiac phenotypes. We studied the in vivo activity of the alpha-MHC promoter (
      2564 to +421 bp of the transcriptional start site) by directly injecting a
      recombinant expression plasmid (pAM3LUC) into the ventricular tissue of
      coarctated animals as well as into the unloaded heterotopic transplanted heart.
      When expressed as a function of the activity of a constitutively active viral
      promoter (pSVCAT), pAM3LUC activities were 18.4 +/- 2.9, 24.6 +/- 2.6, and 25.0
      +/- 4.5 (x10(4)) luciferase/chloramphenicol acetyltransferase units in the
      hypertrophied ventricles of 2-, 3-, and 7-day coarctated animals, respectively.
      These values were not statistically different from pAM3LUC activity in control
      hearts of sham operated animals even though alpha-MHC mRNA content was decreased
      by 54% in the hypertrophied myocardium. This disparity between transcriptional
      activity and mRNA content suggests that alpha-MHC expression in the hypertrophic
      ventricle is in part regulated by a posttranscriptional mechanism. In contrast,
      alpha-MHC promoter activity in the unloaded transplanted hearts decreased
      significantly by 37% compared to control working hearts and suggests that a
      transcriptional mechanism of regulation of the alpha-MHC gene may account for the
      phenotypic expression observed in the unloaded myocardium.

PMID- 8159770
TI  - The Epstein-Barr virus (EBV) small RNA EBER1 binds and relocalizes ribosomal
      protein L22 in EBV-infected human B lymphocytes.
AB  - Epstein-Barr virus (EBV), an oncogenic herpesvirus, encodes two small RNAs
      (EBERs) that are expressed at high levels during latent transformation of human B
      lymphocytes. Here we report that a 15-kDa cellular protein called EAP (for EBER
      associated protein), previously shown to bind EBER1, is in fact the ribosomal
      protein L22. Approximately half of the L22 in EBV-positive cells is contained
      within the EBER1 ribonucleoprotein (RNP) particle, whereas the other half
      residues in monoribosomes and polysomes. Immunofluorescence with anti-L22
      antibodies demonstrates that L22 is localized in the cytoplasm and the nucleoli
      of uninfected human cells, as expected, whereas EBV-positive lymphocytes also
      show strong nucleoplasmic staining. In situ hybridization indicates that the EBER
      RNPs are predominantly nucleoplasmic, suggesting that L22 relocalization
      correlates with binding to EBER1 in vivo. Since incubation of uninfected cell
      extracts with excess EBER1 RNA does not remove L22 from preexisting ribosomes, in
      vivo binding of L22 by EBER1 may precede ribosome assembly. The gene encoding L22
      has recently been identified as the target of a chromosomal translocation in
      certain patients with leukemia, suggesting that L22 levels may be a determinant
      in cell transformation.

PMID- 8159772
TI  - Voltage-dependent Ca2+ influx into right-side-out plasma membrane vesicles
      isolated from wheat roots: characterization of a putative Ca2+ channel.
AB  - We report on the identification of a voltage-dependent Ca2+ transport system that
      mediates Ca2+ influx across the plasma membrane (PM) of wheat (Triticum aestivum)
      root cells. The experimental approach involved the imposition of transmembrane
      electrical potentials (via K+ diffusion potentials) in populations of purified,
      right-side-out PM vesicles isolated from wheat roots. Using 45Ca2+ to quantify
      Ca2+ influx into the PM vesicles, the voltage-dependent characteristics of Ca2+
      transport were found to be similar to those exhibited by L-type voltage-gated
      Ca2+ channels in animal cells. The putative PM Ca2+ channel opened upon
      depolarization of the membrane potential, and Ca2+ flux increased to a maximum
      upon further depolarization and then decreased back to zero upon further
      successive depolarizations. This channel was found to be selective for Ca2+ over
      Mg2+, Sr2+, K+, and Na+; was blocked by very low concentrations of La3+; was
      unaffected by high concentrations of the K+ channel blocker tetraethylammonium;
      and exhibited Michaelis-Menten-type transport kinetics. Based on these transport
      properties, we argue that this transport system is a PM Ca2+ channel. We suggest
      that the use of radiotracer flux analysis of voltage-clamped PM vesicles derived
      from plant roots is a straightforward approach for the characterization of
      certain voltage-gated ion channels functioning in cellular membranes of higher
      plant cells.

PMID- 8159773
TI  - [Nonprescription laxatives--the technological viewpoint].

PMID- 8159774
TI  - [Laxatives--structural and pharmacologic aspects].

PMID- 8159775
TI  - [Designer drugs--the phencyclidine series].

PMID- 8159778
TI  - PET studies of presynaptic monoamine metabolism in depressed patients and healthy
      volunteers.
AB  - No deranged presynaptic monoamine metabolism in the brain has been directly
      demonstrated in mood disorders, in spite of the rich but indirect pharmacological
      evidence for a decreased efficacy of monoaminergic synaptic transmission in
      depression, especially as for serotonin. The availability of 11C-labelled 5
      hydroxytryptophan (5-HTP) and L-DOPA, the direct precursors in the synthetic
      pathways to serotonin and dopamine, has allowed positron emission tomographic
      (PET) studies in 8 healthy volunteers and 6 patients suffering from unipolar
      depression. Main results indicate (1) decreased uptake of [11C]5-HTP and [11C]L
      DOPA over the blood-brain barrier in depression (which is not altered by dietary
      tryptophan depletion in healthy volunteers), and (2) an increased utilization of
      [11C]5-HTP (but not [11C]L-DOPA), in the lower region of the medial prefrontal
      cortex, mainly of the left side. This phenomenon presumably mirrors an increased
      synthesis of serotonin in this area and might represent a local compensatory
      increase in a situation of a general serotonergic hypometabolism. Analyses of
      interactions of both ligands between striatal and prefrontal areas suggest
      significantly stronger positive correlations in depression than in health, that
      could be interpreted as a less pronounced autonomy between brain regions in
      depression.

PMID- 8159776
TI  - Disproportionate loss of noradrenergic and cholinergic neurons as cause of
      depression in Alzheimer's disease--a hypothesis.
AB  - Forty-two patients with neuropathologically confirmed Alzheimer's disease, who
      had been examined prospectively, had a significant decrease of neuron numbers in
      the locus coeruleus, substantia nigra, and basal nucleus of Meynert compared to
      10 age-matched, non-demented controls. A subgroup of 12 demented patients with a
      history of depression had significantly lower neuron numbers in the locus
      coeruleus and slightly higher neuronal density in the basal nucleus of Meynert.
      We hypothesize that a noradrenergic/cholinergic imbalance may promote the
      development of depressive features in patients with Alzheimer's disease.

PMID- 8159779
TI  - The growth hormone response to baclofen in obsessive compulsive disorder: does
      the GABA-B receptor mediate obsessive anxiety?
AB  - The growth hormone (GH) response to the gamma amino butyric acid type B (GABA-B)
      receptor agonist baclofen was measured in 10 Caucasian out-patients with DSM-III
      R obsessive compulsive disorder (OCD) and 10 healthy comparison subjects. The
      patients also underwent a dexamethasone suppression test. The GH response was
      similar in both groups and there was a low rate of dexamethasone non-suppression
      in the patients. The data do not suggest that GABA-B receptor dysfunction is a
      feature of obsessive anxiety.

PMID- 8159777
TI  - Expression cloning of a serotonin transporter: a new way to study antidepressant
      drugs.
AB  - Tricyclic antidepressants revolutionized the treatment of depression. These
      results and the monoamine-depleting effect of reserpine have contributed to the
      proposal that an imbalance in monoamines is a causal factor in depression. Most
      antidepressants act to concentrate monoamines in the synapse either by blocking
      metabolism via monoamine oxidase or by inhibiting reuptake by plasma membrane
      transporters. We have used a novel cDNA expression cloning strategy to isolate
      cDNAs for the antidepressant-sensitive serotonin transporter and for a reserpine
      sensitive vesicular monoamine transporter which is critical for packaging
      serotonin, dopamine, norepinephrine, epinephrine and histamine into synaptic
      vesicles and secretory granules. In addition, we have isolated a dopamine
      transporter. The three papers summarized here describe the molecular
      characteristics of three proteins critical for monoamine neurotransmission and
      which are targets for antidepressant and psychostimulant drugs. The cloning of
      the serotonin and dopamine transporters and of the CNS vesicular transporter
      provide new tools to examine how post-translational and transcriptional
      regulation of these transporters effect uptake, storage and release of monoamines
      in normal and disease states. In addition to providing substrates for further
      drug discovery, isolation of human homologues should be useful for assessing the
      possible genetic bases of depression.

PMID- 8159780
TI  - Liberation of lithium from sustained release preparations. A comparison of seven
      registered brands.
AB  - We investigated the rate of release of seven commercial lithium preparations
      designated as sustained-release preparations and available in Europe and the USA.
      The examined products release lithium completely within four hours. The rate of
      liberation from three drugs resembles that of nonsustained-release preparations,
      three of which were tested under the same conditions. In one case, the comparison
      between two batches of sustained-release preparations reveals marked differences
      in quality. Physicians should be aware that some drugs available on the market
      and designated as sustained-release preparations do not comply with the
      international standard for this type of formulation.

PMID- 8159781
TI  - Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile
      dementia of the Alzheimer type (SDAT).
AB  - Cerebrolysin is a peptidergic nootropic drug with a multimodal mechanism of
      action. It is expected to have a positive influence on neurodegenerative diseases
      such as senile dementia of the Alzheimer type (SDAT). Experimental studies have
      shown Cerebrolysin to have a regulatory effect on energy metabolism, a positive
      influence on behavior through neuromodulation due to its peptide fraction, and
      most important, a neurotrophic stimulation. In SDAT and related disorders the
      neurotrophic effect of the drug could play a major role and influence the
      progress of the illness. A placebo-controlled double-blind trial was designed to
      examine the efficacy of the drug in SDAT. Confirmatory statistics were used for
      analysis. 120 subjects with mild to moderate dementia according to the Global
      Deterioration Scale (GDS) were included in the trial. Their performance on the
      Mini Mental State Examination (MMSE) was between 15 and 25. The diagnosis was
      substantiated by the Hachinski Ischemic Score and cranial computed tomography.
      The inclusion and exclusion criteria were formulated so as to prevent a
      distortion between the two arms by secondary dementia or other disease. The two
      arms received either placebo or the drug once a day (30 ml Cerebrolysin in 100 ml
      physiological saline i.v.) from Monday to Friday for four weeks. Physiological
      saline (130 ml) was used as placebo. Primary variables used for the statistical
      analysis were the Clinical Global Impression (CGI), which measures the
      improvement in symptoms, the SCAG score, and the performance in the trial-making
      test (ZVT-G). The self-assessment in the Bf-S and the activities of daily living
      in the NAI were used as secondary variables.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159782
TI  - Effect of clozapine on plasma nortriptyline concentration.

PMID- 8159783
TI  - Genetic influences on EEG sleep and the human circadian clock. A twin study.
AB  - The study of neuroendocrine and sleep abnormalities in major depressive disorders
      has been the focus of major interest in the past few years. However, while sleep
      and neuroendocrine research in neuropsychiatric disorders has progressed
      considerably during the last few years, conceptional and methodological advances
      in sleep and neuroendocrine physiology are still needed for further understanding
      of the basic aspects of sleep and to clarify the control and significance of the
      temporal fluctuations of the neuroendocrine systems. In particular,
      identification of the genetic mechanisms governing sleep regulation are of
      interest. In this respect, twin studies constitute a powerful method for
      identifying genetic influences on human physiological variables. In a first
      study, we explored the sleep patterns of 26 pairs of noncohabiting normal male
      twins (both mono- and dizygotic). The results indicate that a significant genetic
      effect is found for some sleep variables. Stages 2, 4, and delta sleep as well as
      waking are substantially determined by genetic factors, in contrast to stage REM
      which seems to be mainly affected by nongenetic influences. These data thus
      provide consistent evidence that some aspects of human sleep are genetically
      determined. In a second study we analyzed the 24-hour profile of plasma cortisol
      in 21 pairs of male twins. The 24-hour profile of plasma cortisol is the most
      widely used marker of the human circadian clock: Its study offers the possibility
      of assessing the status of the human circadian clock and of determining whether
      genetic factors affect human circadian rhythmicity. In the protocol, blood was
      sampled every 15 min and circadian rhythmicity was characterized by measures of
      amplitude, phase, and overall waveshape.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159784
TI  - Cloning and characterization of a cDNA encoding aspartate aminotransferase-P1
      from Lupinus angustifolius root tips.
AB  - A root tip cDNA library, constructed in the lambda Zap II expression vector, was
      immunoscreened with a monoclonal antibody raised against aspartate
      aminotransferase-P1 from Lupinus angustifolius L. var Uniharvest. One 1452-base
      pair clone was isolated. The encoded protein sequence had high homology to both
      plant and animal aspartate aminotransferase sequences. The clone was converted to
      the phagemid form and expressed in Escherichia coli. The expressed protein was
      enzymically active and could be immunocomplexed with aspartate aminotransferase
      P1-specific antibodies. The complete aspartate aminotransferase-P1 cDNA was
      cloned into the yeast expression vector pEMBL-yex4 and transformed into
      Saccharomyces cerevisiae strain BRSCS6, which possesses a mutated aspartate
      aminotransferase gene (the asp5 mutation). Complementation of the mutation was
      achieved using this construct.

PMID- 8159785
TI  - Cloning and sequence analysis of a cDNA encoding ferric leghemoglobin reductase
      from soybean nodules.
AB  - A cDNA encoding soybean (Glycine max [L.] Merr) ferric leghemoglobin reductase
      (FLbR), an enzyme that is postulated to play an important role in maintaining
      leghemoglobin in its functional ferrous state, has been cloned and characterized.
      A group of highly degenerate oligonucleotides deduced from the N-terminal amino
      acid sequence of FLbR was used to prime the polymerase chain reaction (PCR) on
      soybean nodule mRNA and cDNA. A full-length clone of FLbR cDNA was isolated by
      screening a lambda gt11 soybean nodule cDNA library using the specific PCR
      amplified FLbR cDNA fragment as a probe. The cDNA contained about 1.8 kb and had
      a coding sequence for 523 amino acids with a predicted molecular mass of 55,729
      D, which included a putative 30-residue signal peptide and a 493-residue mature
      protein. Computer-aided analysis of the deduced FLbR amino acid sequence showed
      considerable homology (varied from 20-50% with enzymes and species) to
      dihydrolipoamide dehydrogenase (EC 1.8.1.4), glutathione reductase (EC 1.6.4.2),
      mercuric reductase (EC 1.16.1.1), and trypanothione reductase (EC 1.6.4.8) in a
      superfamily of pyridine nucleotide-disulfide oxidoreductases from various
      organisms. Northern blot analysis using FLbR cDNA as a probe showed that the FLbR
      gene was expressed in soybean nodules, leaves, roots, and stems, with a greater
      level of expression in nodules and leaves than in roots and stems. Southern blot
      analysis of the genomic DNA showed the presence of two homologous FLbR genes in
      the soybean genome.

PMID- 8159787
TI  - Comparative study of cellulases associated with adventitious root initiation,
      apical buds, and leaf, flower, and pod abscission zones in soybean.
AB  - Cellulase activity was measured in soybean (Glycine max) leaf abscission zones,
      flower abscission zones, pod abscission zones, apical buds, and adventitious
      rooting hypocotyls. Immunoprecipitation data showed that a cellulase
      immunologically similar to the bean abscission cellulase (isoelectric point 9.5)
      is present in soybean leaf, flower, and pod abscission zones, but is not present
      in soybean apical buds or rooting hypocotyls. cDNA and genomic clones for two
      different soybean genes were identified and show sequence similarity with the
      bean abscission cellulase clone pBAC10. The cDNA clone pSAC1, isolated from a
      soybean abscission cDNA library, hybridized to transcripts in soybean leaf,
      flower, and pod abscission zones. Although ethylene has been shown to play a role
      in the increase in cellulase activity associated with both abscission and
      adventitious root initiation, no signal was seen for hybridization of the soybean
      abscission cellulase clone, pSAC1, to RNA from soybean adventitious rooting
      hypocotyls. In addition, no soybean abscission cellulase transcripts were
      detected in apical buds. Transcripts for a second soybean cellulase gene (SC2)
      were not detected in any of the tissues surveyed.

PMID- 8159786
TI  - Synechocystis PCC 6803 contains a single gene for the beta subunit of tryptophan
      synthase with strong homology to the trpB genes of Arabidopsis and maize (Zea
      mays L.).
AB  - We report the sequence of the trpB gene of the cyanobacterium Synechocystis sp.
      PCC 6803. This gene was cloned from a plasmid library by functional
      complementation of a trpB mutant of Escherichia coli K-12. Among the known trpB
      sequences, the Synechocystis gene bears the greatest homology to the duplicated
      trpB genes of Arabidopsis thaliana and Zea mays. Southern and northern blotting
      analyses suggest that Synechocystis contains only a single trpB gene. In contrast
      to all other prokaryotes, Synechocystis has a trpB gene that is monocistronic.
      Attempts to construct a trpB null mutant of Synechocystis by standard techniques
      were unsuccessful, suggesting that this organism is unable to concentrate
      tryptophan from the external medium.

PMID- 8159789
TI  - Characterization of a family of chlorophyll-deficient wheat (Triticum) and barley
      (Hordeum vulgare) mutants with defects in the magnesium-insertion step of
      chlorophyll biosynthesis.
AB  - During thylakoid membrane biogenesis, chlorophyll (Chl) biosynthesis and the
      accumulation of Chl-binding proteins are tightly linked, light-regulated
      processes. We have investigated the consequences faced by mutant plants with
      defects in Chl biosynthesis by studying a series of five homeologous allelic
      chlorina mutants in wheat (Triticum) and one phenotypically related barley
      (Hordeum vulgare) mutant that express the same pleiotropic mutant phenotype but
      to different extents. These mutants accumulate Chl at different rates, with the
      most severely affected plants having the slowest rate of Chl accumulation.
      Analysis of precursor pools in the Chl synthesis pathway indicates they have a
      partial block in Chl synthesis and accumulate protoporphyrin IX (Proto), the last
      porphyrin compound common to both heme and Chl synthesis. The affected plants
      with the most severe phenotypes accumulate the most Proto. Chloroplasts isolated
      from these mutants exhibit a lower activity of the enzyme Mg-chelatase, which
      catalyzes the first committed step in Chl synthesis. The most severely affected
      plants exhibit the greatest reduction in Mg-chelatase activity. Heme levels and
      protoporphyrinogen oxidase activity were the same for mutant and wild-type
      plants. We suggest that a block in Mg-chelatase activity in these mutants could
      account for the other traits of their pleiotropic phenotype previously described
      in the literature.

PMID- 8159788
TI  - A small GTP-binding protein from Arabidopsis thaliana functionally complements
      the yeast YPT6 null mutant.
AB  - A clone designated A.t.RAB6 encoding a small GTP-binding protein was isolated
      from a cDNA library of Arabidopsis thaliana leaf tissue. The predicted amino acid
      sequence was highly homologous to the mammalian and yeast counterparts, H.Rab6
      and Ryh1/Ypt6, respectively. Lesser homology was found between the predicted
      Arabidopsis protein sequence and two small GTP-binding proteins isolated from
      plant species (44% homology to Zea mays Ypt1 and 43% homology to Nicotiana
      tabacum Rab5). Conserved stretches in the deduced amino acid sequence of A.t.Rab6
      include four regions involved in GTP-binding, an effector region, and C-terminal
      cysteine residues required for prenylation and subsequent membrane attachment.
      Northern blot analysis demonstrated that A.t.Rab6 mRNA was expressed in root,
      leaf, stem, and flower tissues from A. thaliana with the highest levels present
      in roots. Escherichia coli produced histidine-tagged A.t.Rab6 protein-bound GTP,
      whereas a mutation in one of the guanine nucleotide-binding sites (asparagine122
      to isoleucine) rendered it incapable of binding GTP. Functionally, the A.t.RAB6
      gene was able to complement the temperature-sensitive phenotype of the YPT6 null
      mutant in yeast. The isolation of this gene will aid in the dissection of the
      machinery involved in soluble protein sorting at the trans-Golgi network of
      plants.

PMID- 8159790
TI  - 3,4-Dehydroproline inhibits cell wall assembly and cell division in tobacco
      protoplasts.
AB  - We investigated the function of cell wall hydroxyproline-rich glycoproteins by
      observing the effects of a selective inhibitor of prolyl hydroxylase, 3,4-dehydro
      L-proline (Dhp), on wall regeneration by Nicotiana tabacum mesophyll cell
      protoplasts. Protoplasts treated with micromolar concentrations of Dhp do not
      develop osmotic stability and do not initiate mitosis. The architecture of
      regenerated cell walls was examined using deep-etch, freeze-fracture electron
      microscopy of rapidly frozen tobacco cells. Untreated protoplasts assemble a
      dense fibrillar cell wall consisting of laterally associating subelementary
      fibrils. In contrast, treatment of protoplasts with Dhp alters the structure of
      the regenerated wall fibrils in several ways: first, the microfibrils are coated
      with globular knobs; second, some larger fiber bundles have an open ribbon-like
      appearance; and third, the smallest subelementary fibrils were not visible.
      Tobacco cells develop an abnormal morphology as a consequence of this abnormal
      cell wall structure. Thus, inhibition of prolyl hydroxylase results in the
      regeneration of a cell wall with abnormal structural and functional properties.
      These data provide experimental evidence that hydroxyproline-rich glycoproteins
      are important for the structural integrity of primary cell walls and for the
      correct assembly of other wall polymers, and that wall structure is an important
      regulator of cell division and cell morphology.

PMID- 8159791
TI  - Evidence that sigma factors are components of chloroplast RNA polymerase.
AB  - Plastid genes are transcribed by DNA-dependent RNA polymerase(s), which have been
      incompletely characterized and have been examined in a limited number of species.
      Plastid genomes contain rpoA, rpoB, rpoC1, and rpoC2 coding for alpha, beta,
      beta', and beta" RNA polymerase subunits that are homologous to the alpha, beta,
      and beta' subunits that constitute the core moiety of RNA polymerase in bacteria.
      However, genes with homology to sigma subunits in bacteria have not been found in
      plastid genomes. An antibody directed against the principal sigma subunit of RNA
      polymerase from the cyanobacterium Anabaena sp. PCC 7120 was used to probe
      western blots of purified chloroplast RNA polymerase from maize, rice,
      Chlamydomonas reinhardtii, and Cyanidium caldarium. Chloroplast RNA polymerase
      from maize and rice contained an immunoreactive 64-kD protein. Chloroplast RNA
      polymerase from C. reinhardtii contained immunoreactive 100- and 82-kD proteins,
      and chloroplast RNA polymerase from C. caldarium contained an immunoreactive 32
      kD protein. The elution profile of enzyme activity of both algal chloroplast RNA
      polymerases coeluted from DEAE with the respective immunoreactive proteins,
      indicating that they are components of the enzyme. These results provide
      immunological evidence for sigma-like factors in chloroplast RNA polymerase in
      higher plants and algae.

PMID- 8159792
TI  - Characterization of the auxin-inducible SAUR-AC1 gene for use as a molecular
      genetic tool in Arabidopsis.
AB  - The small auxin up RNA (SAUR) genes were originally characterized in soybean,
      where they encode a set of unstable transcripts that are rapidly induced by
      auxin. In this report, the isolation of a SAUR gene, designated SAUR-AC1, from
      Arabidopsis thaliana (L.) Heynh. ecotype Columbia is described. The promoter of
      the SAUR-AC1 gene contains putative regulatory motifs conserved among soybean
      SAUR promoters, as well as sequences implicated in the regulation of other genes
      in response to auxin. The transcribed region is approximately 500 bp in length
      and contains no introns. Highly conserved sequences located within the SAUR-AC1
      transcript include the central portion of the coding region and a putative mRNA
      instability sequence (DST) located in the 3' untranslated region. Accumulation of
      SAUR-AC1 mRNA is readily induced by natural and synthetic auxins and by the
      translational inhibitor cycloheximide. Moreover, several auxin- and gravity
      response mutants of Arabidopsis exhibit decreased accumulation of the SAUR-AC1
      mRNA in elongating etiolated seedlings. In particular, in the axr2-1 mutant the
      SAUR-AC1 transcript accumulates to less than 5% of wild-type levels. These
      studies indicate that SAUR-AC1 will be a useful probe of auxin-induced gene
      expression in Arabidopsis and will facilitate the functional analysis of both
      transcriptional and posttranscriptional regulatory elements.

PMID- 8159793
TI  - Isolation and characterization of three soybean extensin cDNAs.
AB  - We have characterized three different soybean (Glycine max) mRNAs that encode
      apoproteins of extensins, a family of cell wall hydroxyproline-rich glycoproteins
      (HRGPs). These transcripts encoded distinctive Tyr-rich proteins containing
      characteristic Ser-Pro4 sequences organized in higher-order repetitive units. The
      first transcript encoded an extensin SbHRGP-1 containing the 16-amino acid repeat
      Ser-Pro4-Ser-Pro-Ser-Pro4-Tyr-Val-Tyr-Lys, with Val occasionally replaced by Ile
      or Tyr. The second transcript encoded the SbHRGP-2 protein containing the 16
      amino acid repeat Ser-Pro4-Ser-Pro-Ser-Pro4-Tyr-Tyr-Tyr-Lys/His. The third
      transcript encoded the SbHRGP-3 protein containing a variant of 9- or 10-amino
      acid canonical repeats: Ser-Pro4-Tyr-Lys-Tyr-Pro, Ser-Pro5-Tyr-Lys-Tyr-Pro, and
      Ser-Pro4-Val-Tyr-Lys-Tyr-Lys, respectively. The dramatic amino acid substitutions
      in the Tyr-rich blocks (Tyr-X-Tyr-Lys) among these HRGPs indicate that each
      SbHRGP may have a different function in cell wall architecture.

PMID- 8159794
TI  - A cDNA clone encoding a light-harvesting protein from Mantoniella squamata.

PMID- 8159795
TI  - ESI3, a stress-induced gene from Lophopyrum elongatum.

PMID- 8159796
TI  - Root-inducing region of mikimopine type Ri plasmid pRi1724.

PMID- 8159797
TI  - Nucleotide sequence of a transcript encoding a germin-like protein that is
      present in salt-stressed barley (Hordeum vulgare L.) roots.

PMID- 8159798
TI  - Nucleotide sequence of a soybean (Glycine max L. Merr.) ubiquitin gene.

PMID- 8159799
TI  - Nucleotide sequence of a cDNA encoding an elongation factor (EF-1 alpha) from
      barley primary leaf.

PMID- 8159800
TI  - Arabidopsis gene and cDNA encoding cell-wall invertase.

PMID- 8159801
TI  - An auxin-inducible proteinase inhibitor gene from tomato.

PMID- 8159802
TI  - [Mental disorders in childhood and adolescence].

PMID- 8159803
TI  - Methods of microwave fixation for microscopy. A review of research and clinical
      applications: 1970-1992.
AB  - Microwave fixation methods are important because excellent preservation of both
      cell structure and antigenicity can be attained several orders of magnitude
      faster than by routine chemical fixation methods. Fast and ultrafast microwave
      fixation have yielded significant logistic advantages over another fast fixation
      approach-rapid freezing at liquid helium temperatures. For example, specimens
      used for microwave fixation can be as large as 1 cm3 and cells can remain in
      suspension. We review in detail both qualitative and quantitative morphologic
      results obtained by using microwave fixation in sample preparation. We provide
      tables of biological molecules that are preserved in a variety of human and
      animal tissues by various microwave fixation methods for histochemistry,
      immunohistochemistry, cytochemistry, immunocytochemistry, and affinity labelling
      studies. Limitations of large cavity (e.g., household) microwave ovens often
      result in irreproducible fixation results. We present calibration and
      standardization protocols for microwave fixation in large cavity microwave ovens
      that emphasize a) localization of oven hot spots (i.e., high power) using a neon
      bulb array, b) magnetron warm-up, c) the use of a water load, d) the use of an
      agar-saline-Giemsa model to predict the uniformity of irradiation in small
      samples, e) the use of specimen containers with one dimension less than 1.5 cm,
      and f) fast specimen handling to prevent conductive heating artifacts after
      irradiation. Although microwave ovens are commonplace their unique applications
      in the laboratory environment require special safety considerations, which are
      reviewed. Advances in microwave technology are providing new means to study the
      structure-function relationships of cellular and biochemical activities.

PMID- 8159804
TI  - Effect of epidermal growth factor, transforming growth factor alpha and nerve
      growth factor on gastric mucosal integrity and microcirculation in the rat.
AB  - In the present study we have compared the effects of the peptide growth factors
      epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and
      nerve growth factor (NGF) on gastric mucosal integrity and mucosal blood flow in
      the rat. Mucosal damage was assessed 30 min after intraluminal instillation of
      40% (w/v) ethanol (EtOH). EtOH treatment resulted in an increase in mucosal
      damage when compared to saline treated control animals. Administration of each
      growth factor either by tail vein (i.v.; 0.2-1 nmol/kg) or via the left gastric
      artery (i.a.; 0.05-0.2 nmol/kg) resulted in a significant reduction in the extent
      of mucosal damage. The growth factors reduced EtOH-mediated damage in an
      equipotent manner. The reduction in the area hemorrhagic damage ranged from -25
      to -35% from EtOH alone when the factors were administered i.a. and from -75 to 
      85% when delivered i.v. Gastric mucosal blood flow as assessed by laser Doppler
      flowmetry (LDF) was increased in a dose-dependent and equipotent manner by EGF
      and TGF alpha administered either by the i.v. or i.a. route. LDF changes were
      greater when EGF or TGF alpha were delivered via the i.a. route. NGF did not
      significantly increase blood flow regardless of the dose or route of delivery.
      beta-Adrenoceptor blockade with propranolol (0.75 mg/kg i.v.) abolished the
      increase in LDF in response to EGF or TGF alpha but did not affect the ability of
      these growth factors to reduce EtOH-mediated damage.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8159805
TI  - Purification of a novel DBI processing product, DBI39-75, and characterization of
      its binding site in rat brain.
AB  - This report describes the purification and characterization from rat brain of
      DBI39-75, a novel, biologically active processing product of diazepam binding
      inhibitor (DBI). We have shown that DBI39-75 in nM concentrations stimulates
      pregnenolone synthesis in mitochondria of rat brain. Using cross-linking of 125I
      DBI39-75 in steroidogenically active concentrations we have demonstrated for the
      first time that the DBI fragment has a specific high affinity binding site in rat
      brain. Displacement of [3H]PK 11195 and [3H]Ro5-4864 by DBI39-75 indicates more
      complex interaction than the competitive inhibition. Collectively, the data
      suggest that the function of DBI39-75 is mediated through a mitochondrial
      receptor complex which includes binding sites for PK 11195 and Ro5-4864.

PMID- 8159806
TI  - Relationship between postprandial release of CCK and PP in health and in chronic
      pancreatitis.
AB  - The aim of this study was to investigate the relationship between postprandial
      release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in healthy
      subjects and patients with chronic pancreatitis (CP). 14 patients with CP and 14
      age-matched healthy subjects were studied. Diagnosis of CP was confirmed by
      standardized imaging modalities (ERCP and CT). Exocrine pancreatic function was
      assessed in all 28 subjects using the pancreolauryl serum test (PLT). An oral
      test meal was administered to stimulate endogenous hormone release. Plasma
      samples were taken before and at several time points after the test meal. CCK and
      PP plasma levels were measured by specific radioimmunoassays. Basal CCK and PP
      plasma levels were not different between patients with CP and controls, and were
      not correlated in either group. However, a direct linear correlation between
      integrated postprandial release of CCK and PP was found in healthy subjects (r =
      0.74, P < 0.005). This postprandial coupling was not evident in patients with CP
      (r = 0.16; n.s.). Peak fluorescein serum concentration in patients with CP and
      steatorrhea (SCP) (n = 6) was < 2.5 micrograms/ml, and CCK and PP responses to
      the meal were significantly impaired (CCK response = 61 +/- 14 pmol/l/120 min in
      SCP vs. 110 +/- 14 in controls, P < 0.05; PP response = 3920 +/- 1773 pg/ml/120
      min in SCP vs. 13418 +/- 3299 in controls, P < 0.05). In patients with
      mild/moderate exocrine insufficiency, CCK and PP responses varied greatly and
      were not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159807
TI  - Sequencing and characterization of trypsin modulating oostatic factor (TMOF) from
      the ovaries of the grey fleshfly, Neobellieria (Sarcophaga) bullata.
AB  - Injection of crude extracts of late vitellogenic ovaries into staged females of
      the grey fleshfly Neobellieria (Sarcophaga) bullata inhibited oocyte development
      and biosynthesis of trypsin-like enzymes in the gut. Trypsin synthesis in N.
      bullata is cyclic and is correlated with egg development, which is discontinuous.
      A trypsin modulating oostatic factor (Neb-TMOF) was purified from 10,000
      vitellogenic ovaries and sequenced by mass spectrometry. Neb-TMOF is a
      hexapeptide (NH2-NPTNLH-COOH). Injection of the hormone at physiological
      concentrations (10(-9) M), inhibited trypsin-like synthesis by the midgut of
      liver-fed female flies, and caused a reduction of the vitellogenin concentration
      in the hemolymph and of oocyte growth. The role of Neb-TMOF in controlling egg
      development and the physiological similarities with Aedes-TMOF are discussed.

PMID- 8159808
TI  - Glycine-extended post-translational processing intermediates of gastrin and
      cholecystokinin in the gut.
AB  - Cholecystokinin (CCK) and gastrin are two polypeptide hormones of the gut that
      share complete structural homology in their carboxyl-terminal pentapeptide. Both
      peptides are biologically activated from their glycine-extended precursor forms
      by a carboxyl-terminal alpha-amidation reaction. In the present studies we used
      region specific antisera to characterize the carboxyl-terminally amidated and
      glycine-extended forms of gastrin and CCK in mammalian intestine. Multiple
      amidated molecular forms of gastrin and CCK and their corresponding glycine
      extended forms were detected throughout the most of the small bowel. Although, we
      detected substantial amounts of glycine-extended CCK in the proximal rat
      duodenum, we detected none of the corresponding amidated molecular forms. In
      contrast, the proximal duodenum of dog and hog contained both glycine-extended
      and amidated CCK. These findings suggest that there may be peptide, tissue and
      species specific differences in expression and activity of the peptide alpha
      amidating enzyme.

PMID- 8159809
TI  - Coteratogenic effects of caffeine.
AB  - Coteratogenicity studies have been carried out using various physical and
      chemical agents along with caffeine. For ionizing radiation in mice, enhancement
      of teratogenic responses (cleft palate, limb malformations) was noted with single
      systemic bolus doses of 50 to 200 mg/kg. Studies in rats with ethanol or nicotine
      reveal only an additive effect with caffeine. There are mixed results with
      chemical carcinogens and caffeine with some studies showing enhancement and
      others showing that caffeine inhibits the teratogenic effect of some carcinogens.
      The time of treatment, at the time of carcinogen exposure for the inhibition and
      later in the gestation period for the enhancement, appears to be the critical
      factor. For a variety of pharmaceutical agents (acetazolamide, mitomycin C,
      hydroxyurea, 5-fluorouracil), caffeine was shown to enhance the teratogenic
      effect of the agent. With 5-azacytidine in rats, caffeine suppressed limb
      malformations. Administration of inhibitors of beta-adrenergic function reduces
      the teratogenic effect of caffeine in mice. The interpretation of the
      experimental studies in terms of human hazard is complicated by the general use
      of high-dose bolus exposures which are not typical of human exposures, and the
      use of test systems that are not readily applicable to humans. The studies in
      human populations show clearly that caffeine itself has no link to negative birth
      outcome, and in the few instances where it has been examined there appears to be
      no interaction between coffee consumption and either alcohol consumption or
      smoking on pregnancy outcome.

PMID- 8159810
TI  - Another flaw in the linearized multistage model upper bounds on human cancer
      potency.
AB  - The statistical methodology used by the EPA and other federal agencies to
      characterize human cancer potencies based on animal experiments greatly
      exaggerates the estimates and bounds for human cancer risks in some instances.
      The current methodology incorporates simplified assumptions and approximations
      that fail to properly assess the impact of quantitative differences in human and
      experimental animal background transition rates from stage to stage in the
      multistage carcinogenic process. Because the majority of tumorigenic responses in
      rats and mice occur in organs with a high background tumor incidence and, hence,
      high background stage transition rates, the current simplified methodology often
      significantly overstates human risk. This newly recognized flaw in conjunction
      with the several previously recognized flaws in the current characterizations of
      human cancer potencies argues strongly for a change away from the current
      characterizations based solely on a default screening methodology to a more
      comprehensive, biologically based risk assessment methodology.

PMID- 8159811
TI  - Regulatory oversight of biochemical pesticides by the U.S. Environmental
      Protection Agency: health effects considerations.
AB  - The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) enables the
      Office of Pesticide Programs (OPP) of the U.S. Environmental Protection Agency to
      ensure that pesticide use in commerce will not result in unreasonable adverse
      effects to humans and the environment. Currently, two classes of pesticides are
      recognized: conventional chemical pesticides and biological pesticides. The
      latter group is divided into biochemical and microbial pesticides. The recent
      resurgence of biochemical pesticides as effective pest control agents has
      increased the number of applications for experimental use permits and for product
      registration. The fundamental information and data necessary to evaluate such
      products by the Health Effects Division (HED) of OPP are discussed, as well as
      the criteria for the classification of a pesticide as a biochemical versus a
      conventional chemical pesticide. In accordance with the Agency's effort to
      encourage the development of pesticides less toxic to humans and the environment,
      the scientific basis for providing future regulatory relief and reduced data
      requirements for biochemical pesticides is discussed.

PMID- 8159812
TI  - Risk assessment of carcinogenic chemicals in The Netherlands. Health Council of
      The Netherlands: Committee on the Evaluation of the Carcinogenicity of Chemical
      Substances.
AB  - The Health Council of The Netherlands advises the Dutch government on scientific
      issues concerning health and environmental protection. In 1978 a committee of the
      Council established mechanistic criteria for quantitative risk assessment of
      carcinogenic substances. For this purpose it adopted the multistage model of
      carcinogenesis. Based on this model two categories of carcinogens were
      distinguished. The first category includes complete carcinogens and tumor
      initiators; these agents induce irreversible modification of DNA and act by a
      stochastic mechanism. The second category includes promoters and other substances
      acting as cocarcinogens; these agents act by nonstochastic mechanisms. Stochastic
      action implies that there is no threshold for the contribution to the
      carcinogenic effect, whereas nonstochastic action implies a threshold dose.
      Recently, reevaluation of the method for carcinogenic risk assessment was
      considered due because of remarkable scientific progress since 1978, such as the
      identification of cellular oncogenes and tumor suppressor genes, and the partial
      clarification of mechanisms at the cellular and/or molecular level by which tumor
      promoters stimulate tumor development. The present paper discusses the Dutch
      method for carcinogenic risk assessment in the light of the recent scientific
      developments. It concludes that this method for risk assessment is still a valid
      and appropriate one.

PMID- 8159813
TI  - Setting health-protective soil concentrations for dermal contact allergens: a
      proposed methodology.
AB  - Health-based cleanup goals for contaminated soils are typically established to
      protect potentially exposed individuals from increased incidences of cancer and
      serious noncancer effects. However, at least one regulatory agency has suggested
      that, for certain contact allergens such as hexavalent chromium, soil remedial
      goals should also consider the potential occurrence of allergic contact
      dermatitis (ACD) in sensitized individuals (NJDEPE, 1992). To date, appropriate
      risk assessment methods for setting ACD-based soil concentrations have not been
      addressed in the scientific literature. This paper defines and discusses the
      three key data needs for establishing ACD-based soil concentrations: (1) dose
      response data from human patch-testing studies, in which the patch concentrations
      are reported in terms of mass of allergen per unit area of skin, (2) accurate
      estimates of the degree to which soil adheres to skin on a soil mass per unit
      area of skin basis, and (3) accurate estimates of the degree to which the
      allergen leaches from soil into human sweat. The requisite basis for each of
      these factors and suggested methods for obtaining and evaluating the necessary
      data are presented. In addition, two example calculations are presented for
      setting ACD-based goals for hexavalent and trivalent chromium in chromite ore
      processing residues.

PMID- 8159814
TI  - Improved method for selection of the NOAEL.
AB  - The paper proposes that the NOAEL be defined as the highest dosage tested that is
      statistically significantly different from the control group while also being
      statistically significantly different from the LOAEL. This new definition
      requires that the NOAEL be defined from two points of reference rather than the
      current approach (i.e., single point of reference) in which the NOAEL represents
      only the highest dosage not statistically significantly different from the
      control group. This proposal is necessary in order to differentiate NOAELs which
      are statistically distinguishable from the LOAEL. Under the new regime only those
      satisfying both criteria would be designated a true NOAEL while those satisfying
      only one criteria (i.e., not statistically significant different from the control
      group) would be designated a "quasi" NOAEL and handled differently (i.e., via an
      uncertainty factor) for risk assessment purposes.

PMID- 8159815
TI  - A rational approach to risk assessment requires the use of biological
      information: an analysis of the National Toxicology Program (NTP), final report
      of the advisory review by the NTP Board of Scientific Counselors.
AB  - The National Toxicology Program (NTP) Board of Scientific Counselors met on April
      14 and 15, 1992 to review the NTP. This paper provides an overview of the Board's
      Report with an emphasis on the recommendations made by the Carcinogenesis Working
      Group. The prime overall recommendation is that the NTP should move from a focus
      on hazard identification to an emphasis on providing the type of biological
      information that needs to be incorporated into the risk assessment process. This
      would involve a hypothesis-driven mechanism of action approach aimed at
      understanding the basis for the actions of the chemicals of interest. Relevant
      examples are provided. Scientists from the National Institute of Environmental
      Health Sciences' (NIEHS) intramural program and those outside of NIEHS should be
      included in the research effort. This strategy would permit a more rational
      approach toward both test development and design (e.g., selection of the high
      dose to be employed), and the interpretation of test results (e.g., addressing
      questions pertaining to dose-response relationships and species to species
      extrapolation). The overall goal would be to provide a reasonable assessment of
      the possible hazard that a chemical might pose to people in light of realistic
      conditions of exposure.

PMID- 8159817
TI  - Two approaches for assessing human safety of disperse blue 1.
AB  - Disperse Blue 1 is an anthraquinone dye used at low levels in semipermanent hair
      color formulations. Dietary administration of Disperse Blue 1 in a National
      Toxicology Program (NTP) carcinogenesis bioassay produced transitional- and
      squamous-cell tumors, leiomyomas, and leiomyosarcomas of the urinary bladders of
      male and female F344/N rats. The occurrence of tumors in the urinary bladder of
      rats was associated with urothelial hyperplasia and the presence of urinary
      calculi. Despite the occurrence of urinary bladder calculi and other
      nonneoplastic changes, there was no evidence of urinary bladder carcinogenesis in
      B6C3F1 mice fed Disperse Blue in the diet for up to 2 years. A study conducted in
      rats of the same strain by Burnett and Squire confirmed the occurrence of calculi
      and transitional-cell neoplasms in the rat bladder. However, no mesenchymal-cell
      tumors were detected at a comparable dietary level. Further, Burnett and Squire
      found evidence of reversibility of the proliferative changes in the rat urinary
      bladder following cessation of treatment at 6 months. Disperse Blue 1 has been
      tested in a variety of in vivo and in vitro genotoxicity assays and was negative
      in vivo but produced a weak and mixed pattern of genotoxic responses in vitro
      which may be attributable to a constituent of the commercial preparations.
      Evaluation of the available data for Disperse Blue 1 and comparison with the
      responses observed in the urinary bladders of rats administered other rodent
      bladder carcinogens considered to act through a secondary mechanism indicate that
      a threshold approach is appropriate for assessing risk. With this approach, an
      uncertainty factor of 1000 applied to the no-observed-adverse-effect level in the
      NTP bioassay yielded a safe exposure level of 45-56 micrograms/kg/day. In
      contrast, with a conventional quantitative risk assessment approach, the exposure
      level corresponding to an upper limit on lifetime risk of 10(-6) to 10(-5) was
      0.39 to 3.9 micrograms/kg/day, respectively. The safe level of Disperse Blue 1
      derived using the threshold approach is approximately 20 times greater than the
      maximum average daily applied dose of 2.7 micrograms/kg/day associated with its
      use in semipermanent hair color formulations, while the exposure associated with
      the 10(-5) risk level using the linearized multistage model in the conventional
      approach was determined to be 1.5 times greater. Because oral absorption is
      substantially more than dermal absorption, the actual margin of safety is most
      likely much greater than either of these comparisons suggests.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8159816
TI  - The toxic oil syndrome: a perspective on immunotoxicological mechanisms.
AB  - The etiologic agents responsible for the development of autoimmune diseases are
      generally unknown. Clearly, developing an understanding of causative agents will
      be essential for the development of strategies for therapy, if not prevention, of
      these health problems. The immune system is a target of many toxicants, including
      those obtained through diet. One important example of the immunologic effect of
      dietary toxins is provided by the toxic oil syndrome (TOS). The intentional
      denaturation of rapeseed oil with aniline resulted in the production of fatty
      acid anilides. The unintentional consumption of this adulterated oil in Spain
      caused a mass poisoning whose effects continue to the present. Among other
      clinical signs, a majority of TOS patients had characteristics of type 1
      hypersensitivities. A smaller number of people developed symptoms of autoimmune
      diseases including scleroderma. These observations highlight the probability that
      environmental chemicals may be a major source of etiologic agents for autoimmune
      disease. In this review, the authors provide an overview of some of the more
      important features of TOS as they pertain to immunity. The authors also speculate
      on the immunopathologic mechanisms by which the TOS progressed, with emphasis on
      oxidative stress as a central byproduct of anilide-induced injury.

PMID- 8159818
TI  - A reexamination of the low prevalence of carcinogens in an early carcinogen
      screen.
AB  - In 1969 Innes et al. reported that 9% of 127 industrial chemicals and pesticides
      (including 7 positive controls) tested in a mouse bioassay were carcinogenic by
      oral administration. This is much lower than the prevalence of approximately 50%
      that has been found recently by the cancer bioassays conducted under the aegis of
      the U.S. National Toxicology Program (NTP) or reported in Carcinogen Potency Data
      Base compiled by Gold and collaborators. Using the CASE structure-activity
      relational expert system and the NTP cancer bioassay results as a learning set,
      we found that the predicted prevalence of carcinogens among the chemicals tested
      by Innes et al. is 62.7%. It is concluded that the bioassay protocol used by
      Innes et al. is less sensitive than the subsequently adopted bioassay procedures.

PMID- 8159819
TI  - [The hepatitis B virus in alcoholic liver disease: its clinical and biochemical
      assessment].
AB  - The aim of our work was to study the prevalence of HBV markers in Alcoholic Liver
      Disease (ALD) by evaluating clinical and biochemical parameters that could
      further characterize the association. A prospective and sequential study of 107
      patients with ALD was performed, including 83 cases of cirrhosis and 24 cases of
      alcoholic hepatitis. Daily ingestion of pure ethanol was of at least 70 gm for
      seven years or more and always associated with hepatocellular disfunction.
      According to the serological profile for HBV markers the patients were allocated
      to one of four groups: group I infected (positivity of HBsAg and anti-HBc); group
      II immunized (positivity of anti-HBs and anti-HBc); group III without HBV markers
      (negativity of HBsAg, anti-HBc and anti-HBs); group IV isolated anti-HBc. The
      prevalence of HBsAg positivity in ALD was high: 15.89% whereas immunity was low:
      26.17% suggesting a great exposure to the virus and a deficient immunological
      response. No significant statistical differences were found among the three
      groups when clinical and biochemical parameters were individually considered.
      Nevertheless, when a Child/Campbell classification was applied, patients with ALD
      associated with HBV (group I) showed a significant difference, presenting a
      predominance of child C, with a bad prognosis.

PMID- 8159820
TI  - Longitudinal study of the indirect immunofluorescence and complement fixation
      tests for diagnosis of Chagas' disease in immunosuppressed patients submitted to
      renal transplantation.
AB  - Clinical and serological follow-up of 7 patients submitted to renal
      transplantation and presenting positive serological reactions to Chagas' disease
      before immunosuppression did not show significant changes in indirect
      immunofluorescence and complement fixation titres for Chagas' disease, or signs
      and symptoms indicating exacerbation of the disease during follow-up. In
      addition, 18 of 66 recipients of renal transplants considered to be non-chagasic
      before immunosuppression showed at least one positive result to the indirect
      immunofluorescence test for Chagas' disease during the study period. The results
      suggest that the immunosuppression state induced in chagasic patients submitted
      to renal transplant did not promoted exacerbation of the chronic infection in
      these patients and not interfere with the serological response of chronic
      chagasics, thus permitting the use of these serologic reactions for diagnostic
      purposes in these cases. However, the positive results of the indirect
      immunofluorescence test in non-chagasic patients indicate the need for judicious
      interpretation of the indirect immunofluorescence test for the diagnosis of
      Chagas' disease in renal transplanted patients.

PMID- 8159821
TI  - [The evolution of in-vitro resistance in Plasmodium falciparum to antimalarials
      in a gold-prospecting area in the state of Amapa between 1983 and 199)].
AB  - This study evaluates the sensitivity of P. falciparum in vitro to antimalarial
      drugs in an area of gold mining exploration in Amapa State during the period of
      1983 to 1990. The following tests were done, 75 in vitro studies with chloroquine
      and quinine, 74 with amodiaquine and 76 with mefloquine. The results showed 81%
      of resistance to chloroquine and 27% to amodiaquine while resistant strains to
      quinine and mefloquine were found. Also for these two quinolinomethanols a loss
      of sensitivity was noticed in the period of study. An association between
      resistance to chloroquine and decrease of sensitivity to quinine was also evident
      with the same strains.

PMID- 8159822
TI  - [The prevalence of Demodex folliculorum and Demodex brevis in a population sample
      from Botucatu, Sao Paulo, Brazil].
AB  - A survey was conducted to determine the prevalence of D. folliculorum and D.
      brevis for the first time in Brazil. In this study, association between the
      presence of mites and host factors (age, sex and race) were analysed. Samples
      were obtained from 100 individuals submitted to a facial cleaning in an aesthetic
      clinic in Botucatu city. All the samples were mounted in Berlese's medium and
      examined by dark-field phase microscopy. From 100 studied individuals, 72 were
      positive, among the positive cases, 51% showed D. folliculorum, 2% showed D.
      brevis and 19% both species. The parasite distribution in relation to sex was not
      taken in account because the sex ratio favoured females (90%). According to age,
      prevalence was high in all age groups. The factors influencing this distribution
      could be due. 1. the examination of extensive skin areas, 2. the group examined
      composed of individuals in treatment in an anaesthetic clinic could be more
      infested than a normal population, 3. the fact that in tropics, the prevalence is
      often high in all ages.

PMID- 8159823
TI  - Growth and differentiation on a trypanosome of the subgenus Schizotrypanum from
      the bat Phyllostomus hastatus.
AB  - The effects of temperature, pH, osmolarity and aeration on the growth and
      differentiation of a trypanosome of the subgenus Schizotrypanum isolated from the
      bat Phyllostomus hastatus were studied. In general, the growth characteristics of
      the flagellate were similar to those of Trypanosoma (Schizotrypanum) cruzi.
      However, the parasite did not growth at 33 or 37 C. Increase in the osmolarity
      and aeration promoted growth at 33 C. Significant metacyclogenesis was detected
      only in the growth condition where maximal growth occurred (28 C, pH 7.3, 380
      mOs/kg, in tissue culture flasks), at the end of the exponential growth phase.
      The beginning of the metacyclogenesis process was coincident with most glucose
      utilization and lowest pH. During metacyclogenesis both culture medium pH and
      osmolarity increased steadily.

PMID- 8159824
TI  - [Acute Chagas' disease in an 80-year-old woman in Mexico. An
      anatomicopathological report].
AB  - A case of acute Chagas' disease, diagnosed by necropsy, in a 80-year-old woman,
      is reported. It is assumed that infection was acquired through triatomine bite in
      Zacoelo de Torres, Jalisco State, Mexico. There were lesions due to Aoffican
      trypanosomiasis in the heart, esophagus and bowel. Autonomic nervous lesions were
      detected in the esophagus and bowel. It is emphasized the importance of these
      findings in an area where few cases of megas were reported.

PMID- 8159825
TI  - Labrea-like hepatitis in Vitoria, Espirito Santo State, Brazil: report of a case.
AB  - A case of fulminant hepatitis with microvesicular steatosis resembling Labrea's
      fever, diagnosed in Vitoria (ES) is reported. The 16 year old boy presented with
      severe epistaxis, agitation, jaundice and hemorrhagic vomiting and died two days
      after admission to the emergency unit of the University Hospital. The disease
      started five days before with fever, myalgias, dark urine and jaundice and
      progressed with psychic agitation, torpor and coma. The liver and spleen were not
      palpable. HBsAg was negative in the serum. The autopsy showed acute hepatitis
      with lytic necrosis confluent in the midzonal and periportal areas with massive
      microvesicular steatosis in the remaining hepatocytes. Mononuclear cells
      predominated in the exudate. The reticulum showed condensation in the necrotic
      areas without typical bands of collapse. The portal tracts were edematous with
      mononuclear infiltration and mild bile duct proliferation. Absence of
      cholestasis. Except for the confluent midzonal and periportal necrosis this case
      showed several clinical and morphological aspects of the Labrea fever described
      from the East Amazon, demonstrating that the anatomical picture of this disease
      probably is not in related to a factor peculiar to the Amazon region.

PMID- 8159826
TI  - [Chronic Chagas' cardiopathy causing congestive heart failure in childhood: a
      clinical and histopathological study of a case with emphasis on the lesions of
      the intracardiac conduction and autonomic nervous systems].
AB  - A case of decompensated chagasic cardiopathy in a nine-year-old boy from the
      south of the State of Goias, is described. He developed congestive heart failure
      four months before death. The serological reaction for Chagas' disease and the
      xenodiagnosis were positive. Electrocardiograms showed sinusal tachycardia,
      ventricular and supraventricular extrasystoles, left anterior hemiblock, complete
      right bundle branch block and signs of chambers overload. The echocardiogram
      demonstrated chamber dilatation with diffuse hypocontractility. He presented a
      downhill course complicated with several pneumonic episodes, the last one just
      before death. At necropsy, the heart, exhibited a chronic pancarditis with
      fibrosing chronic myocarditis involving mainly the interventricular septum and
      left ventricle. The heart conduction system showed slight to moderate exudative,
      inflammatory changes. Scattered foci of slight chronic periganglionitis and rare
      degenerative phenomena of ganglionic cells were found in intracardiac autonomic
      nervous, without neuronal depopulation.

PMID- 8159827
TI  - [Experimental research on the possibility of the transmission of Toxoplasma
      gondii infection via milk].

PMID- 8159828
TI  - [Experimental hamster infection by Trypanosoma cruzi: the chronic phase].

PMID- 8159829
TI  - Probable podoconiosis in Brasilia.

PMID- 8159830
TI  - [Multiple symmetrical lipomatosis. Metabolic effects of excision of lipomatous
      tissue].
AB  - Multiple Symmetric Lipomatosis (MSL) is a syndrome characterized by the
      occurrence of symmetric lipomas over various regions of the body. No clear
      etiology has been recognized while a frequent association with systemic metabolic
      abnormalities has been described. The metabolic situation of a subject affected
      by MSL was assessed before and after surgical excision of lipomas. A condition of
      impaired glucose tolerance (IGT) was verified both before and after surgery by
      the performance of oral glucose tolerance test, glucagon test, and daily glucose
      profile. No significant differences were observed after the ablation of
      lipomatous masses with regard to glucose, IRI, IRCP and NEFA behaviour. We
      concluded that the resection of lipomas can not modify glucose tolerance in MSL
      and that lipomas can be considered as tissues metabolically independent from the
      rest of body fat.

PMID- 8159831
TI  - The nightly spontaneous alkalinization of the stomach.
AB  - Authors evaluated eighty-four 24-hour intragastric pH recordings of 73 subjects
      in different pathophysiologic conditions. Among them there were 12 healthy
      subjects, 27 duodenal ulcer patients, 10 of whom were examined both before and
      after treatment with H2 receptor antagonists, 18 gastro-esophageal refluxers and
      16 other patients who complained of dyspepsia of various origins. Authors
      observed a spontaneous nocturnal alkalinization phenomenon of the stomach (SNA)
      which began in the latter part of the night; its onset was strongly related with
      sleeping and interrupted by waking up. This phenomenon was absent in duodenal
      ulcer patients but could be restored by treatment with anti-H2 drugs. The
      authors, moreover, gave evidences of a relation between SNA and the vagal
      integrity and modulation of the gastric secretions.

PMID- 8159832
TI  - Long-term treatment with rifaximin and lactobacilli in post-diverticulitic
      stenoses of the colon.
AB  - The authors report their endoscopic experience in the treatment of intestinal
      inflammatory complications and their prevention with cyclic antibiotic treatment
      (rifaximin 400 mg b.i.d. for 7 days/month), followed by recolonizing treatment
      with lactobacilli (2 capsules in the morning for 7 days/month), for an overall
      period of 12 months. In all 79 cases (45 males and 34 females, mean age 63 years,
      range 55-75 years), the treatment proved capable of controlling the symptoms and
      averting the onset of the complications which follow attacks of acute
      diverticulitis. These complications include uncontrollable sepsis, free
      perforation of a hollow viscus, evolutive fistulation, intestinal occlusion,
      abscesses not drained percutaneously, all factors which necessitate urgent
      elective surgery. Rifaximin, together with lactobacillus treatment, proved to be
      effective, well-tolerated and safe, and can thus be considered an indispensable
      aid in the treatment of diverticular disease and in the prevention of its
      complications.

PMID- 8159833
TI  - [Mammary reconstruction after subcutaneous mammectomy and simple mastectomy: our
      technical orientation].
AB  - The authors present their technical guidelines about the operative procedure for
      high risk benign breast lesions. Various reconstructive managements, conditioned
      by aesthetical-oncological evaluations, are proposed.

PMID- 8159834
TI  - [82 mammary reconstructions immediately after subcutaneous mammectomy or after
      simple mastectomy. Critical evaluation of results].
AB  - The authors review their experience on 25 patients subjected to bilateral
      subcutaneous mastectomy and 16 patients subjected to bilateral simple mastectomy
      with immediate submuscular insertion of prosthesis for high risk benign breast
      lesions. The best aesthetic results were observed with subcutaneous mastectomy
      (and immediate reconstruction by prosthesis) in patients with small-middle non
      ptotic breasts. In addition, the authors believe that high risk lesions in large
      breast are better treated with simple mastectomy and immediate reconstruction by
      tissue expander.

PMID- 8159836
TI  - [Clinical considerations in the use of nifedipine in patients with "HELLP
      syndrome"].
AB  - The authors report eleven cases of patients having pregnancy induced
      hypertension, and two cases of patients having severe pregnancy induced
      hypertension complicated by thrombocytopenia, and elevated liver enzymes.
      Nifedipine has been used in treatment of blood hypertension. Moreover, nifedipine
      appeared to reverse thrombocytopenia and serum liver enzymes. The authors discuss
      the significance of Hellp syndrome (haemolysis, elevated liver Enzymes, and low
      platelet count).

PMID- 8159835
TI  - [Antibiotic prophylaxis in cardiovascular surgery: comparison of sulbactam
      ampicillin and cefuroxime].
AB  - A total of 200 patients (131 males and 69 females), scheduled for cardiovascular
      surgery were randomly assigned to receive either sulbactam/ampicillin 1 g IV of
      cefuroxime 2 g IV before the surgical incision and then, postoperatively, 8
      hourly x 3 days. There were five failure of prophylaxis (all in the cefuroxime
      group): 3 sternal incision abscesses (1 Pseudomonas aeruginosa and 2
      Staphylococcus epidermidis), one urinary tract infection (Staphylococcus aureus)
      and one Micrococcus pneumoniae. Tolerance to both antibiotics was excellent. In
      our sample of patients, the efficacy and safety of sulbactam/ampicillin were not
      different from those of cefuroxime in prophylaxis in cardiovascular surgery.

PMID- 8159837
TI  - Education, knowledge and metabolic control in children with type 1 diabetes.
AB  - We studied thirty diabetic patients and we evaluated their knowledge of main
      topics of diabetes mellitus. The level of the knowledge was evaluated by multiple
      choice questionnaires. On the basis of score obtained the patients were divided
      into two groups: Group A, with high knowledge level, Group B, with low knowledge
      level. All the patients were followed-up for a 12 months period after a careful
      education. At the end of follow-up, we compared the Group A patients with another
      group of 14 diabetic children, who have followed an educational programme from
      the diagnosis of the disease (Group C). We assessed the knowledge score and the
      principal metabolic parameters in the three groups of patients; during the follow
      up, we found a significant increase of these parameters in Group A and B
      patients, more evident in Group A patients. At the end of follow-up, the Group C
      patients showed a higher knowledge score and metabolic parameters than the Group
      A children. This study shows that education of disease is important for the
      increase of metabolic parameters and its usefulness is higher if is carried out
      from the onset of the disease.

PMID- 8159838
TI  - [Bioethics and drug experimentation in hospitalized patients].
AB  - The authors discuss about clinical experimentation with drugs involving
      hospitalized subjects in consideration of four principles of Bioethics: Autonomy,
      Beneficence, Non Maleficence and Justice. This article explores also the problems
      linked to the application of good clinical practice according to the European and
      Italian recent rules. Human integrity, respect of patient's dignity, informed
      consent, correct methods, placebo, Ethics committees represent the essential
      basis for those researchers that intend conduct clinical trials really "with
      subject and not on the subject".

PMID- 8159839
TI  - A study on hypertension in schoolchildren.
AB  - This form wants to be an instrument to carry out rapidly and correctly the
      hypertension's screening in school-children. The school-physician, or anybody
      else who takes care of school-child, will find these outlines easy to follow.
      Nevertheless a strict methodology has to be used. The family history for
      hypertension, obesity, hypercholesterolemia, diabetes mellitus and cardiovascular
      diseases is also considered, as well as heart rate, somatic growth and physical
      activity. Subjects with elevated blood pressure levels should be sent to a second
      level Center for appropriate investigations and follow-up.

PMID- 8159840
TI  - [Autoclaved tumoral autografts. Apropos of 12 cases, 6 of which highly
      malignant].
AB  - Twelve patients presenting with a bone tumor were operated on using autoclaved
      bone autografts for reconstruction following carcinologic resection. According to
      the Enneking grading system, 6 were high malignancy tumors (3 osteosarcomas and 3
      grade 2 chondrosarcomas), 4 were low grade tumors (1 paraosteal sarcoma, 1
      chondrosarcoma, 1 secondary chondrosarcoma, 1 liposarcoma). One was a metastasis
      from a kidney tumor. The last patient had a femoral osteoid osteoma. Six local
      recurrences were responsible for 4 reoperations: 2 disarticulations and 2
      iterative resections. With a 1-6 years range of follow-up (average follow-up 2.5
      years), osseointegration of autoclaved grafts was studied. Fusion at the
      host/graft junction was roentgenographically observed. In three cases, proximal
      resorption of the humeral graft occurred. Five biopsies were obtained during
      reoperation after 1 year, which showed partial revascularization of autoclaved
      bone autografts. The authors conclude that autoclaved tumoral bone grafts, are
      reliable and discuss indications. They point out the main contraindication,
      represented by chemosensitive bone tumors, in which conservation of the removed
      tumor is necessary to quantify the response to chemotherapy.

PMID- 8159841
TI  - [Aneurysmal cyst of the bones in children].
AB  - The authors have analysed a series of aneurysmal bone cysts (A.B.C.) in children
      and adolescents which were reviewed at an average follow-up of 4 years 2 months
      (6 months-15 years). The average age at diagnosis was 8 years (3-19 years).
      Pathological fractures were the main reason for consultation, probably due to the
      predominance of central lesions. If conventional radiology remains indispensable
      to diagnosis, magnetic resonance imaging is nevertheless the most important
      examination in determining the extent of the affection. The diagnosis remains
      anatomopathological, even if this may be difficult due to associated lesions
      (A.B.C. illness and A.B.C. symptoms). In long bones lesions, we observed
      recurrence after curettage in 3 out of 7 cases. For this reason the recommend
      simple resection or reconstructive resection rather than curettage whenever
      possible. 5 lesions in contact with growth plate were observed. In such cases we
      recommend its conservation by careful curettage, especially in young children. We
      feel that subsequent recurrence is easier to treat than an epiphysiodesis bridge.
      The surgical techniques employed to conserve the plate are described along with
      methods of bone reconstruction after surgery.

PMID- 8159842
TI  - [Radiologic evaluation of the rotation center of the hip].
AB  - We studied 98 normal hips in 54 patients in order to assess precise settlement of
      the theorical hip center using the U landmark as reference i.e. determine A
      distance (vertical settlement) and C distance (horizontal settlement)) A being
      the vertical distance between U landmark and the femoral head center, C the
      horizontal distance between U landmark and the femoral head center. We found two
      indexes (A/E = 0.2 and C/D = 0.3) which allowed us to fix that center in vertical
      (A/E) and in horizontal (C/D) direction even in case of bilateral hip dysplasia,
      and which can be used either in pre-operative planning or in post-operative
      evaluation. D being the horizontal distance between the U landmarks, and E the
      vertical one between the U landmark and the sacroiliac joint.

PMID- 8159843
TI  - [Fractures of a single bone of the forearm in children].
AB  - A series of 69 one bone forearm fractures in children is reported. Thirty six
      ulna and 33 radius were involved. Average age was 7.6 years. The fracture type
      varied: compression fracture in 2 cases, greenstick fracture in 45 cases and
      impacted fracture in 22 cases. For 25 cases, a plastic bowing of the other
      forearm bone was associated. Treatment was immobilization without reduction (53),
      or reduction with anesthesia (16). One proximal radial fracture was treated with
      medullary nailing the 15th day, after 2 secondary displacements. Early
      radiological results were very good in 40 per cent, good in 32 per cent, fair in
      19 per cent, and poor in 7 per cent. Eleven children with a poor or fair initial
      result had clinical and radiological evaluation with long term follow-up;
      functional and radiological results were always good or very good. The reduction
      of the plastic deformity as reported by Sanders allowed to achieve better early
      results.

PMID- 8159844
TI  - [Pseudarthrosis of the uncinate process].
AB  - Ten cases of nonunion of the hook of the hamate were observed, eight of which had
      occurred during athletic activity. The mean age was 31.1 years and the mean
      length of time between the accident and diagnosis was 8.8 months. Diagnosis was
      most often confirmed by CT scanning, which, represents the examination of choice.
      In all cases, surgical treatment was applied using the same technique and the
      same surgeon. Results were evaluated according to resolution of pain, movement,
      strength of grip and return to former level of athletic activity. Results were
      very good in six patients and good in two others who returned to previous
      activity. One patient had only a fair result with resolution of pain. One case
      was a failure with persistence of pain and ulnar paralysis.

PMID- 8159845
TI  - [Gentamycin impregnated plaster beads in the treatment of bone infection].
AB  - The authors have used gentamycin impregnated plaster beads in the treatment of
      409 chronic osteomyelitis. This technic was associated with large surgical
      excisions of the septic area, stabilization of the focus and coverage using
      flaps. About 95 per cent of the patients were cured after a 37 month average
      follow-up. About 4 per cent were failures with recurrence of drainage. Complete
      filling of the bone loss was obtained in 42 per cent of the cases. In 16 per cent
      it was less than one third of the bone loss. It is concluded that this technique
      allowing an immediate filling of the bone loss using a resorbable material and
      leading to high antibiotic concentrations is reliable.

PMID- 8159846
TI  - [Osteoid osteoma of the sigmoid notch of the ulna].
AB  - We report one case of osteoid-osteoma (0.0.) developed in the radio-ulnar
      proximal joint in a young male adult. The initial diagnosis had been chronic
      epicondylitis evolving since two years. A surgical detachment of the muscle from
      the epicondylus lateralis humeri had even been performed with no result driving
      to contemplate again the initial diagnosis which was corrected by
      tomodensitometry and surgical exploration. Excision has obtained immediate pain
      relief and after a one year follow up there was no recurrence. The diagnostic
      problems raised by intra articular 0.0. of the elbow are discussed.

PMID- 8159847
TI  - [Idiopathic acro-osteolysis. Apropos of a case with carpal-tarsal onset].
AB  - This work reports an isolated case of idiopathic acro-osteolysis with a carpo
      tarsian onset without associated nephropathy, diagnosed in a 16 year-old patient.
      It has raised problems of etiologic diagnosis, of classification and therapeutic
      behaviour in the presence of destructive lesions with an extensive and
      progressive evolution.

PMID- 8159848
TI  - [Intramuscular hematoma simulating a pseudomalignant tumor].
AB  - One case of a large post-traumatic cystic haematoma of the thigh presenting with
      a pseudotumoral aspect, and resulting in a femoral filling defect and a
      spontaneous fracture 7 years later, is reported by the authors. Relationships
      between its pathophysiology and its consequences on bone are stressed.

PMID- 8159849
TI  - [An unusual cause of fracture of the femoral neck: bone sarcoidosis].
AB  - A case of pathological fracture of the femoral neck in a 84-year old female is
      presented. The histological examination of the femoral head showed sarcoidosis.
      This diagnosis was not known before the trauma. Other localisations of bone
      sarcoidosis were found in the tarsus and the fingers after a systematic X-ray
      check-up.

PMID- 8159850
TI  - [An evaluation of the knowledge, perceptions and feelings of cancer patients in
      relation to their disease and the health team].
AB  - The authors through individual interviews have analyzed the way cancer patients
      got to know about their illness and how these information influenced their lives,
      family and their feelings. Suggestions have been made after evaluating the
      results reached in this research.

PMID- 8159851
TI  - [The epidemiological situation of Hansen's disease and its contacts in Campinas].
AB  - Leprosy is a highly prevalent, endemic disease in this country. Due to its long
      evolution, it gives rise to an extremely important social issue. This paper
      analyses the epidemiologic status of Leprosy in the municipality of Campinas. The
      epidemiologic framework indicates that control of leprosy communicants in
      Campinas remains inefficient, showing the need for further studies upon these
      social actors, important links in the epidemiologic sequence of this disease.

PMID- 8159852
TI  - [The perception by nurses of the activities performed in their work units].
AB  - The goal of this study is to verify the activities of unit nurses and ambulatory
      nurses in governmental hospital and to know they perceive these activities. The
      population was composed by 19 nurses of both units. The data was collect using
      structured interviews, and analysed in quantitative and qualitative dimensions.
      The results demonstrated that nurses work as routine activities, based in
      tradition and authority and there was no reflection about practice, causing a
      reiterative practice.

PMID- 8159853
TI  - [The trend in the locus of control in diabetic patients].
AB  - The tendency of locus of control in diabetic patients is a theme approached by
      the nurse as an educator. The objectives of this study was to test reliability of
      the "Instrumento de Medida de Locus de Controle a Saude (IMLCS)" (Instrument of
      Measurement of Locus of Control for Health); to confront the distribution of
      responses to different items of the "IMLCS" by a group of diabetic patients; and
      to verify the predominance of locus of control for health in the subjects
      studied. To reach these objectives the "IMLCS" was applied. The data showed that
      there was a prevalence of subjects with a locus of external control, that the
      different items were answered in a favorable manner by the subjects and that the
      scale was valid for the population of diabetic patients. We believe that these
      results show the need for rethinking the role of the nurse in the education of
      diabetic patients.

PMID- 8159854
TI  - [The measurement of the psychomotor capacities involved in the technic of the
      intramuscular injection].
AB  - This study is to verify the psychomotor skill using psychomotor capacity measure.
      The authors describe two tests that will be used by nurses denominated
      "electronic psychomotor" and "perferation". Those tests are applied in the first
      stage of this study to analyse the teaching-learning process of intramuscular
      injection. Three groups of undergraduate nursing students in different stages of
      evolution of the course, were analysed and were verified that there was
      homogeneity among groups in relation to psychomotor capacity.

PMID- 8159855
TI  - [The degree student and scientific research].
AB  - Investigation about the perception and knowledge of the nursing graduation
      students with respect to scientific research and its use. The method is
      qualitative-analysis of the contents. The environment is a public nursing school
      in Rio de Janeiro, the sample consists of 36 students and the tool is a list of 6
      questions. The students have a relative scientific research knowledge absorbed
      along the graduation, mainly from 6th period. They think that the scientific
      method is important to their development. They choose Research Introduction
      course as a manner of learning, to develop monographs, to increase their
      professional skill and to get credits.

PMID- 8159856
TI  - [The feelings related to the self-image of elderly patients undergoing amputation
      of the limbs].
AB  - The present study is part of the DIOGO monograph, and has the intention of
      verifying with aged people who have been submitted to amputation of inferior
      limbs, the sentiments related with their self-image. The data was collected from
      25 infirmary and hospitalized patients, of a governmental university hospital.
      The analysis of the results suggests that the sentiments shown by the patients
      submitted to amputation less than 10 days before were different from those shown
      by patients which had suffered amputation over a month before, while dependence
      was manifested in both groups. In relation to the reactions of relatives and
      friends, both groups were similar.

PMID- 8159857
TI  - [Analgesia in cancer: beliefs and an update].
AB  - Cancer pain relief is not yet adequate, but there are resources for this.
      Professional's misconception and the tabu about that pain in cancer is inevitable
      have been contributing to this problem. Important nurses' knowledge lacuna about
      pain relief in cancer was found by this study. The WHO program about pain relief
      in cancer is presented too.

PMID- 8159858
TI  - A quality-of-life index for clients with ischemic heart disease: establishing
      reliability and validity.
AB  - This article describes the method the authors will use to develop a valid and
      reliable instrument to measure quality of life as an outcome measure of a cardiac
      rehabilitation program. A discussion of the difficulties in conceptualizing and
      measuring quality of life and a summary of the contribution of prior studies to
      the development of the instrument are presented. Implications for cardiovascular
      nursing practice are also discussed.

PMID- 8159859
TI  - Ticlopidine hydrochloride: its current use in cerebrovascular disease.
AB  - It is estimated that half a million Americans will suffer strokes this year
      (National Stroke Association, 1989). The physical, emotional, and financial
      impacts of such an event are enormous. While stroke treatment methods have
      improved and rehabilitation programs have expanded, a substantial number of
      stroke patients are left with major disabilities. The only way to intervene is to
      focus on stroke prevention through the identification and modification of risk
      factors. One such intervention involves antiplatelet therapy, which has been
      found to reduce the risk of initial thrombotic stroke and the potential for
      recurrent stroke. Nurses caring for stroke patients need to know about this type
      of therapy, because continuity of pharmacological treatment, patient compliance,
      and education are essential for adequate stroke prevention.

PMID- 8159860
TI  - Scabies outbreak on a spinal cord injury unit.
AB  - This article describes an outbreak of scabies on a 30-bed acute spinal cord
      injury unit and the measures taken to eradicate the infestation. Because spinal
      cord injury patients have sensorimotor deficits, the sensation of itching often
      is absent, making an infestation of scabies more difficult to identify. A total
      of 30 patients and 38 employees were exposed and treated for scabies. Educational
      programs about scabies were instituted immediately for all employees. Routine
      daily activities and therapy schedules were severely hampered by the outbreak.
      Despite the efforts of staff to solve the problems associated with the outbreak,
      frustration and anger were sometimes displayed by many of the staff, patients,
      and families because of the difficulties they encountered. The outbreak was
      halted, however, and no further cases were reported, although several employees
      had to be treated twice.

PMID- 8159861
TI  - Assessing cognitive function: a guide to neuropsychological testing.
AB  - Neuropsychology is a discipline that studies brain-behavior relations through
      laboratory testing of behavior. Neuropsychologists develop a comprehensive
      clinical description of the person's cognitive processes and their implications
      for everyday behavior. Nurses can use the results of neuropsychological
      assessments as an objective source of information when planning care for clients
      who are cognitively impaired. This article provides an introduction to
      neuropsychology as a discipline, to its tests, and to its methods of assessment
      and interpretation. Two standard test batteries, the Halstead-Reitan Battery and
      the Luria-Nebraska Neuropsychological Battery, are described. Special tests for
      many cognitive functions--such as attention, executive functions, sensation and
      perception, motor performance, memory, language, and intelligence--also are
      described.

PMID- 8159862
TI  - Changes in body image secondary to disease and injury.
AB  - This article describes the relationship between body image and self-concept,
      discusses responses to changes in body image secondary to disease and injury, and
      explores strategies for adjustment to alterations in body image.
      Sociopsychological aspects of body image form a complex framework by which an
      individual understands the self and perceives how he or she is understood by
      others. As body image, self-concept, identity, and ego are closely associated, a
      loss of or alteration in any one of these factors can have deleterious effects on
      the entire self. Rehabilitation professionals assume an important role in helping
      people adjust to and accept alterations in body image by facilitating the
      grieving process; addressing loss, anxiety, and depression; and empowering
      individuals to emphasize and use their assets.

PMID- 8159863
TI  - Patients with chronic obstructive pulmonary disease: their beliefs about measures
      that increase activity tolerance.
AB  - This article describes an exploratory study whose purpose was to examine the
      impact of attitudes and beliefs on the intentions of adult patients with chronic
      obstructive pulmonary disease (COPD) to engage in endeavors that enhance activity
      tolerance. A convenience sample of 32 patients was interviewed using a
      semistructured format. Personal, normative, and control beliefs about endeavors
      that are thought to increase activity tolerance were explored. Using Ethnograph,
      a software package designed for content analysis of qualitative data (Seidel,
      Kjolseth, & Seymour, 1988), the researcher analyzed the interview content to
      identify recurrent themes. The notion of control seemed to be a major influence
      on the intention to engage in measures thought to increase activity tolerance.
      These issues should be explored further with patients who have COPD to help them
      make more effective decisions about their care.

PMID- 8159864
TI  - The power of nursing.

PMID- 8159865
TI  - It can happen to you: dealing with a code situation in the rehabilitation
      setting.

PMID- 8159866
TI  - Head injury issues in The Netherlands and the United States.

PMID- 8159867
TI  - Caring for individuals using home ventilators: an appraisal by family caregivers.
AB  - This article describes a study of the effects of caregiving on family members who
      assumed primary responsibility for managing the care of ventilator-assisted
      individuals in the home. Thirteen caregivers were interviewed and five variables
      associated with their role were assessed: caregiving tasks, burden of caregiving,
      impact of caregiving, mastery of the caregiving role, and satisfaction with
      caregiving. Data were collected using the Caregiving Appraisal Scale (CAS), a
      list of caregiving tasks, and a semistructured interview. Caregivers assumed
      multiple responsibilities for individuals who were completely ventilator
      dependent (n = 5), partially ventilator-dependent (n = 3), or nocturnally
      ventilated (n = 5). Caregivers reported feeling moderate levels of both the
      burden and the negative impact of caregiving but a positive sense of mastery and
      satisfaction. They described problems with home healthcare nurses, insurance
      coverage, and equipment suppliers. Lack of preparation, in terms of education
      provided by healthcare professionals, limited their ability to manage these
      problems quickly and effectively. Caregivers suggested that healthcare providers
      expand discharge planning to include provision of problem-solving strategies.

PMID- 8159868
TI  - Affinities of endotoxin-specific human monoclonal antibodies, their polyclonal
      counterparts and murine monoclonal antibodies.
AB  - Affinity as a measurement of the strength of binding is a crucial factor in
      biological significance. In general, high-affinity antibodies are most effective
      in mediating immunological effector mechanisms. Here, we compare the affinity
      distributions of corresponding polyclonal and monoclonal human antibodies
      specific for lipopolysaccharide determinants of the nosocomial pathogen
      Pseudomonas aeruginosa. The affinities of the 14 human mAb analysed ranged from
      8.3 x 10(5) to 7.5 x 10(8). The average affinities of their polyclonal
      counterparts, assessed by analysing chromatographically separated antibody
      populations, ranged from 1.7 x 10(6) to 6.3 x 10(7). Furthermore, the affinities
      of murine mAb of the same specificity ranged from 3.7 x 10(5) to 1.4 x 10(7).
      These results suggest that the generated human monoclonal anti-carbohydrate
      antibodies exhibit affinities comparable to or higher than those of their human
      polyclonal counterparts and those of murine mAb of the same specificity.

PMID- 8159869
TI  - Differential heat-shock protein synthesis and response to stress in three
      avirulent and virulent Listeria species.
AB  - Two strains of Listeria monocytogenes, a virulent (V) and an avirulent (A) strain
      obtained by repeated in vitro cultivation at 37 degrees C, exhibited differing
      constitutive syntheses of heat-shock proteins (HSP) at 37 degrees C, the
      temperature of the infected host, and a differential response to heat treatment.
      These two strains also reacted differently to addition of a superoxide ion
      inducer and acid to treatments. Our observations were not limited to these two
      strains of L. monocytogenes: the level of HSP synthesis at 37 degrees C varied
      from one species of Listeria to another and was correlated with the thermo
      inducibility of HSP. In an accompanying paper, we will attempt to establish
      whether these different biosynthetic properties observed in vitro between A and V
      L. monocytogenes enable the prediction of their properties/survival once inside
      the resident peritoneal murine macrophages.

PMID- 8159870
TI  - Specificity of leukocyte-endothelial interactions and diapedesis: physiologic and
      therapeutic implications of an active decision process.
AB  - In situ studies have revealed that an active multistep process regulates
      leukocyte-endothelial cell recognition and diapedesis in vivo. The requirement
      for sequential engagement of receptors mediating transient adhesion, leukocyte
      activation, activation-dependent sticking and diapedesis implies that leukocyte
      recruitment can be regulated at any of these 4 steps, and provides a
      combinatorial mechanism to explain the remarkable specificity and diversity of
      leukocyte homing events in vivo. The model will help direct therapeutic
      approaches to controlling leukocyte traffic.

PMID- 8159871
TI  - Lymphocyte adhesion mediated by integrins.

PMID- 8159872
TI  - Sequestration and its discontents: infected erythrocyte-endothelial cell
      interactions in Plasmodium falciparum malaria.

PMID- 8159873
TI  - Vascular adhesion protein-1 (VAP-1)--a new adhesion molecule recruiting
      lymphocytes to sites of inflammation.

PMID- 8159874
TI  - [Metabolic control and the prevalence of dyslipidemia in children and adolescents
      with insulin-dependent diabetes mellitus].
AB  - Cholesterol, triglycerides and lipoprotein levels were assayed in serum of 152
      children and teenagers with IDDM and in 228 non-diabetic siblings. A poor control
      of diabetes, reflected by high levels of glycosylated hemoglobin and/or high
      fasting blood glucose, was associated with statistically significant increases in
      total cholesterol, LDL-cholesterol and triglycerides, and a reduction in HDL
      cholesterol. Mean total cholesterol levels in diabetic patients (171 +/- 33 mg/dL
      for males and 199 +/- 53 mg/dL for females) were statistically higher than those
      in their siblings (158 +/- 30 mg/dL and 164 +/- 33 mg/dL respectively). The
      prevalence of hypercholesterolemia (HC) and hypertriglyceridemia (HTG) were
      higher in the diabetic patients but statistically significant exclusively in
      females (prevalences of 40% vs 12% for HC and 30% vs 9% for HTG with a p value <
      0.005). The diabetic patients in good metabolic control had similar lipid levels
      to those of their non-diabetic siblings. These data support the hypothesis that
      poor control of blood glucose is associated with atherogenic lipid profiles. The
      prevalence of hypercholesterolemia is impressively high in our diabetic
      population and indicates that all IDDM patients should have a serum lipid and
      lipoprotein analysis done annually; blood glucose control and dietary guidelines
      should be improved in these cases.

PMID- 8159875
TI  - [Detection of non-insulin-dependent diabetes mellitus in asymptomatic adults].
AB  - A total of 1,011 clinically asymptomatic adults older than 20 years of age, with
      a minimal fasting of one hour, were screened for diabetes mellitus. This group
      was selected from a community medical service. The presence of diabetes in first
      degree relatives (parents, brothers/sisters and children) was investigated by
      interrogation of the subjects. Weight, height, and the waist and hip perimeters
      were measured, and the body mass index and the waist/hip ratio were calculated.
      Obesity was present in 26% of the population and 35.6% had a relative with
      diabetes mellitus, but 53.8% were younger than 40 years. A capillary blood sample
      was taken and glucose was measured by a reflectometer glucometer. Individuals
      with blood glucose levels of 160 mg/dL or higher were appointed for a fasting
      venous blood sample and glucose was analyzed using the glucose oxidase method. If
      the glucose levels were > 140 mg/dL, a second fasting venous blood sample was
      taken 1-2 weeks later, if both results were > 140 mg/dL a diagnosis of diabetes
      mellitus was established; otherwise it was considered non diagnostic for diabetes
      mellitus. A total of 17 were detected with > 160 mg/dL by the glucometer and
      12/17 persons were diagnosed with diabetes mellitus (1.2%). No person younger
      than 30 years was detected (n = 307), but 3/237 were detected in the thirty years
      group (1.26% for this group) and 9 persons were older than 40 years, 1.2% of the
      total group. Capillary glucose measurements may be used for screening of
      populations selecting those who require to be submitted to diagnostic tests.

PMID- 8159876
TI  - [Bone marrow transplantation in aplastic anemia. Experience at a Mexican
      institution. Bone marrow transplantation group of the Salvador Zubiran National
      Institute of Nutrition].
AB  - During the period of May 1986 through February 1991, nine allogeneic bone marrow
      transplants (BMT) on eight severe aplastic anemia (SAA) patients were performed
      at the Instituto Nacional de la Nutricion Salvador Zubiran in Mexico City. Mean
      age at BMT was 18 years (age interval 12-30); seven were men; all patients had a
      clinical history of multiple blood transfusions; six individuals were infected at
      the time of the transplant. The conditioning regimens were: cyclophosphamide (Cy)
      in three patients; Cy+ total nodal radiation in five; and total nodal radiation
      only in the second transplant of one patient. Graft versus host disease (GVHD)
      prophylaxis was attempted with methotrexate plus cyclosporin A (CsA) in six
      patients, methylprednisolone plus CsA in two, and prednisone + CsA in the patient
      retransplanted. All procedures were carried out under single reverse isolation
      without gut decontamination. Seven of the nine procedures grafted (two cases died
      on days +8 and +25 due to infection). In the surviving, the median time for
      reaching > 1.0 white blood cells x 10(9)/L was 22 days (time interval 11-31); >
      0.5 neutrophils x 10(9)/L in 27 days (time interval 15-42) and the same lapse to
      reach > 50 platelets x 10(9)/L. Length of hospital stay was 42 days (time
      interval 15-61). Acute GVHD was seen in one of the seven patients surviving the
      period of bone marrow aplasia (14%). Of six long term survivors (including one
      patient with a second transplant) chronic GVHD was present in four (67%): chronic
      GVHD was fatal in one individual but was well controlled in three.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8159878
TI  - Reliability of reference models for vital capacity in young Mexican females.
AB  - OBJECTIVE: To assess the reliability of 29 prediction models for vital capacity
      when these are applied as reference for young females, natives and residents in
      Mexico City (altitude = 2,240 m). DESIGN: Transversal, prospective and
      comparative study. SETTING: Metropolitan Autonomous University, Mexico. SUBJECTS:
      Sixty females clinically healthy, 17 to 29 years old, non-smokers. PROCEDURE:
      Vital capacity was predicted from 29 models and measured with a bell spirometer
      (Collins 9 L) according to the American Thoracic Society guidelines. Statistical
      comparison was done between measured and predicted values by linear regression,
      analysis of variance and analysis of residuals. RESULTS: Mean of measured vital
      capacity was 3,625 mL while mean values of predicted vital capacities varied from
      2,644 mL to 3,962 mL. Actual and reference values showed a small but
      significative correlation (r = 0.40 to 0.49). By Dunnett's test, means from six
      of the 29 models showed non-significant differences (p > 0.05) with the mean of
      the measured vital capacity; however, all 29 models presented significative bias
      in the regression line between actual values and the residuals of predicted
      values (correlation coefficient, slope and intercept statistically different from
      zero, p < 0.05). CONCLUSION: Due to the large bias found, models tested in the
      present study have limitations to predict accurate reference values for young
      mexican females.

PMID- 8159877
TI  - [Comparison of two antimicrobial prophylaxis regimens in biliary tract surgery: a
      randomized controlled clinical trial].
AB  - OBJECTIVE: The aim of this study was to analyze the efficacy in prophylaxis
      during biliary tract and gallbladder surgery with amoxicillin/clavulanate and to
      compare it with the combination of cephalothin and clindamycin. DESIGN: A
      randomized nonblinded clinical trial with a blind independent observer. PLACE:
      Tertiary-care center. PATIENTS: Forty-two patients were included. All had
      undergone biliary tract and/or gallbladder surgery. They were divided in two
      groups: 22 in group A (cephalothin and clindamycin), and 20 in group B
      (amoxicillin/clavulanate). INTERVENTIONS: Patients from group A were
      intravenously treated with three doses of cephalothin (2 g at anesthetic
      induction and two additional doses of 1 g at six-hour intervals), and three of
      clindamycin (600 mg every six hours). Patients from group B received three doses
      of amoxicillin/clavulanate (1000/200 mg IV, one during the induction of the
      anesthesia followed by two more at six-hour intervals). RESULTS: In group A six
      wound infections were recorded, one of them with secondary bacteremia. In group B
      we did not record any infection (Fisher p < 0.01). One case of phlebitis was
      recorded in each group. CONCLUSIONS: Our results indicate that
      amoxicillin/clavulanate is useful in the prophylaxis of gallbladder and biliary
      tract surgery, and more effective than the combination of cephalothin and
      clindamycin.

PMID- 8159879
TI  - [Comparison of the DELFIA and RIA methods for measuring luteinizing and follicle
      stimulating hormones in serum].
AB  - Hormonal quantitation has had important developments since Yalow and Berson
      created the first radioimmunoassay for insulin in 1959. Since then much research
      has been done to find new non-isotopic methods which offer better levels of
      sensitivity, specificity and precision than RIA. DELFIA (dissociation enhancement
      lanthanide fluoroimmunoassay) is a new alternative technology which is a specific
      time resolved fluoroimmunoassay (TR-FIA) which combines higher purified antigens,
      monoclonal antibodies in a sandwich type assay with long fluorescence decay time
      of lanthanide chelates as europium, samarium and terbium used as labels, and a
      particular time resolving fluorometer for nanoseconds measurements. As part of
      the validation and introduction of the DELFIA method in our laboratory we made a
      comparative evaluation of DELFIA and RIA in the quantification of serum
      luteinizing hormone and follicle stimulating hormone. The data favor the DELFIA
      method in terms of sensitivity, specificity, volume of sample, half life of
      reagents, as well as the elimination of radioactive tracers.

PMID- 8159880
TI  - [Comparison of the diagnostic usefulness of immunoglobulins A and M in acute
      toxoplasmosis].
AB  - We compared the levels of IgA and IgM antibodies in nonimmunosuppressed patients
      with active toxoplasmosis to evaluate their diagnostic value. In group I (nine
      patients with toxoplasmosis) we determined the presence of anti-toxoplasma
      antibodies at the onset of the disease; in four of them we also studied the
      levels three months later. In group II (control) we tested 50 serum samples from
      healthy subjects. In both groups we investigated the presence of IgG with
      indirect enzyme immunoassay (EIA) (Eti-Toxok G, Sorin Biomedica); capture EIA was
      used to study IgA (Platelia Toxo IgA, Pasteur), and this method (Eti-toxok M,
      Sorin Biomedica) and the capture agglutination technique were used to study IgM
      (Toxo-ISAGA, Biomerieux). The nine patients in group I were positive for IgM
      (Sorin test) but one was negative with the capture agglutination technique and
      for IGA. All nine were positive for IgG, and IgG titers were increased in the
      patients studied a second time. In group II, none of the subjects had IgM; the
      levels of IgG were > 15 IU/mL in 18 subjects, and < or = 15 IU/mL but not absent,
      in the 32 remaining subjects. IgA was detected in eight of the 18 individuals
      with IgG levels > 15 IU/mL and in 11 of the 32 with levels < or = 15 IU/mL. The
      sensitivity of IgA was 88.8% and its specificity 62%; positive and negative
      predictive values were 29.6% and 96.8%, respectively. The assay of IgA in the
      course of active toxoplasmosis does not appear to be a more useful marker than
      IgM detection; however, the study population should be enlarged to include
      patients with reactivations of toxoplasmosis, before we can be more conclusive.

PMID- 8159882
TI  - [Pulmonary alveolar microlithiasis in two siblings].
AB  - The study of two brothers with pulmonary alveolar microlithiasis (MLA) a rare
      lung alteration with autosomic recessive character is presented. In one case the
      lung biopsy made the diagnosis by the identification of multiple calcospherites.
      The importance of the familiar study is stressed, as a sister with the same
      radiographic image was discovered this way. The literature is revised and the
      main data of MLA are presented; the radiologic images and histopathologic
      findings are commented.

PMID- 8159883
TI  - [Pharmacology and toxicology of Guatteria gaumeri and alpha-asarone].
AB  - Guatteria gaumeri Greenman (Annonacease) has been used as bark infusion in the
      traditional mexican medicine for the treatment of hypercholesterolemia and
      cholelithiasis. The main component is alpha-asarone which has been isolated by
      different extraction procedures and subsequently synthetized, as well as 16
      analogs, derivatives of 4-propenyl-1,2-dimethoxybenzenes 5-substituted. After
      daily dosing per os of 80 mg/kg of alpha-asarone and the amino and metoxi analogs
      for seven days to hypercholesterolemic male rats, cholesterol decreased 57.3,
      37.5 and 46.9% and triglycerides diminished 42.5, 67.6 and 17.2% respectively.
      Some of the other analogs showed also important hypolipidemic activity. Similarly
      alpha-asarone decreased 80.6% the weight of gallstones in hamsters. Studies using
      adult rat hepatocytes suggest that at least part of the hypolipidemic effect of
      alpha-asarone could be due to a decrease in the secretion of lipids. Alpha
      asarone did not produce any toxic effect after oral administration to rats of 10
      or 50 mg/kg for 28 days, or genotoxicity by the dominant lethal test. However
      long-term exposure of cultivated hepatocytes to micromolar concentrations
      produced morphologic and ultrastructural alterations, triacylglycerol
      accumulation and inhibition of protein synthesis and secretion. At the same time
      both the Ames and sister-chromatid exchange tests showed genotoxic effect. No
      teratogenicity was observed in pregnant rats during organogenesis but in mice
      slight fetal toxicity was manifested by hydrocephaly, skeletal defects and fetal
      weight retardation. There are no data on the possible exposure levels in humans
      consuming the bark extract, but the toxic effects of alpha-asarone in animals
      suggest caution in the use of this plant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159881
TI  - Ectopic parathyroid adenoma in the posterior triangle of the neck.
AB  - Ectopic parathyroid adenomas are a major cause of persistent hyperparathyroidism.
      They can be located anywhere from the base of the tongue to the mediastinum. We
      describe a patient with hyperparathyroidism from an adenoma in a supernumerary
      gland located in the left posterior triangle of the neck, outside of the carotid
      sheath.

PMID- 8159884
TI  - [Development of the digestive system. Medico-dietetic implications in infants].
AB  - The development of the human gastrointestinal tract starts in early intrauterine
      life. In spite of this early start of the functional differentiation of its
      tissues, the GI tract function is still incomplete at the end of gestation. This
      report reviews the physiological and biochemical aspects of the gastrointestinal
      ontogeny which have medical and dietetical implications in the first year of life
      of infants.

PMID- 8159885
TI  - A call for scholarly review articles.

PMID- 8159886
TI  - Preparedness for clinical nursing education.
AB  - The identification of individualized patient care planning as a core element in
      clinical nursing training showed the need to evaluate how nursing students
      perceive themselves to be prepared for implementing the concept into patient
      care. Ninety-five nursing students, with a mean age of 27 years, participated in
      this study at the end of their first theoretical block. Three questionnaires were
      used; 1) One questionnaire designed for the study concerning demographic data,
      attitudes and valuation of the theoretical education of the nursing process, 2)
      Rosenbaum's Self-Control Schedule, and 3) Antonowsky's Sense of Coherence test.
      The results showed that the students' pre-educational health care experience,
      which varied from one to twenty years, significantly (p < 0.05) influenced the
      evaluation of their preparedness for clinical training. Attitudes towards nursing
      research and development of nursing care were negatively correlated (p < 0.05) to
      their years of previous experience of health care and positively correlated to a
      more theoretical school background. The students' personal preparedness to
      develop independence varied greatly as measured by the Self-Control Schedule and
      the Sense of Coherence test independently of age, work experience and earlier
      education. It was concluded that students might be favoured by individualized
      study planning as a parallel model to individualized care planning.

PMID- 8159887
TI  - Caring for demented elderly in rural primary health care.
AB  - In 1988, the demented in an elderly rural population (n = 851) were traced and
      assessed with the GBS geriatric rating scale. The aim of the study was to
      investigate the level of impairments of demented persons primary cared for and to
      relate their impairments to form of housing; to compare the distribution of care
      between not-demented and demented in an elderly population, and to establish the
      primary caregiver/patient ratio. The majority of the demented (44/50) were cared
      for in the studied primary health care area, despite the scarcity of staff. All
      received formal care. They consumed more formal care than the not-demented in the
      population. In relation to amount of elderly persons helped, the home-help
      personnel ratio was 0.30, in district care the ratio was 0.02, whereas the ratio
      of general practitioners was 0.002, estimated from the number of contacts and
      staff.

PMID- 8159888
TI  - Professionalization--theoretical analysis of the implications for nursing
      practice.
AB  - The aim of the present paper is to examine ideas of professionalization, and to
      explore in what way they might give directions for the development of nursing
      practice. An examination of the literature on professionalization in social
      science reveals that the existing ideas of professionalization may be divided
      into two paradigms, denominated naive paradigm and cynical paradigm. Both
      paradigms have been criticized on the grounds of being idealistic and ahistoric.
      A contemporary view has developed from this criticism, oriented towards the
      historical and social contexts of professions. The implications for nursing
      practice of this view brings into focus the development of nursing practice in
      relation to the public and the tradition of nursing. This view of
      professionalization contributes to a contemporary view of nursing practice, and
      an expanded idea of professionalization is discussed.

PMID- 8159889
TI  - Quality of care. Development of a patient-centred questionnaire based on a
      grounded theory model.
AB  - In a previous study (Wilde et al. 1993), we developed a model of quality of care
      from a patient perspective using a grounded theory approach. The aim of the
      present study was to derive an instrument from this model. A questionnaire,
      Quality from Patients' Perspective (QPP), was developed which consisted of 56
      items. Each item was evaluated in two ways by the respondent; assessment of
      perceived reality and evaluation of subjective importance (Likert scales). A
      personal quality of care index was computed on the basis of the relationship
      between these two scores. The QPP was tested on two samples, patients with
      infectious diseases (n = 147, mean age: 60 years) and nursing students (n = 103,
      mean age: 27 years). Patient's scores were factor analysed (principal factoring
      with oblique rotation) and 17 factors were extracted. Subgroups of patients were
      compared and correlations were computed between factor scores and self-rated
      health and well-being. Students also responded to a short form of the QPP (41
      items) and personality scales. Correlations between these sets of variables were
      computed. The QPP was discussed in relation to existing scales.

PMID- 8159890
TI  - Nursing at dawn. Nursing tasks in the first hour of the morning shift in a German
      hospital.
AB  - Nurses' working hours are known to be one reason for high wastage rates. The
      early start of work seems to be particularly difficult. The aim of the present
      study was to examine which nursing tasks were performed during the time from 6:00
      to 7:00 a.m. The study was conducted in a general hospital in Germany where such
      an early start of work is still common practice. An activity analysis was carried
      out using non-participant observation. One surgical and one medical ward were
      used for comparison. The work on the wards was differently organized. The
      observed tasks were classified into direct care, indirect care, administrative,
      and other tasks. The distribution of these task categories over one hour and the
      percentage of time spent on these categories were compared. Both wards showed
      different working patterns and a different form of initiation of direct care
      (entering patients' rooms). Some possible reasons for these findings are offered
      and suggestions for further research are made.

PMID- 8159891
TI  - Reaching out in nursing.

PMID- 8159892
TI  - Family dynamics and infant temperament in Danish families.
AB  - Transition to parenthood involves the fine balance of family dynamics which both
      affect, and are affected by, the infant's temperament. The purpose of this study
      was to investigate changes in family dynamics over the transition to parenthood
      and the relationship of family dynamics to infant temperament. A sample of 99
      families in Odense, Denmark, completed the Family Dynamics Measure in the third
      trimester of pregnancy and again when the infant was 8-9 months old. At this
      second time, the mothers also completed the Revised Infant Temperament
      Questionnaire. Overall we found small changes, although always in a negative
      direction, in family dynamics over this transition. The largest change was an
      increase in perceived role conflict reported by both mothers and fathers. Mothers
      reported more role conflict than fathers. Positive family dynamics were related
      to infant rhythmicity.

PMID- 8159893
TI  - [What is your diagnosis? Psoriatic arthritis (Synonyms: arthropathic psoriasis,
      psoriatic osteoarthropathy, psoriasis arthritis)].

PMID- 8159894
TI  - [Current aspects of erectile dysfunction--practical aspects].

PMID- 8159895
TI  - [Preoperative magnetic resonance tomography in chronic osteomyelitis of the
      extremities].
AB  - 39 patients with bone and joint infections of the extremities were examined with
      magnetic resonance imaging (MRI) in view of an operative procedure. Patients with
      hip affections and patients with nonoperative treatment were excluded; therefore,
      21 patients including 12 post-traumatic and 9 hematogenous cases of chronic
      osteomyelitis form the study group. MRI findings were verified at operation.
      Typical MRI findings were: intraosseous abscess (n = 15), extraosseous abscess (n
      = 9), communication of both (n = 7), edema of bone marrow (n = 9), soft tissues
      changes (n = 6) and fluid-surrounded sequestrum (n = 6). 83% of the post
      traumatic cases had an intraosseous abscess, 67% of the hematogenous cases an
      edema of bone marrow. MRI improves preoperative planning considerably by
      sensitive depiction of pathological findings in three planes. To obtain
      information about activity of the process, scintigraphy is needed in addition. In
      some cases computer tomography (CT) is helpful to find small sequestra.

PMID- 8159896
TI  - [Gaze paralysis to the right and clouding of consciousness following pelvic
      angiography a patient with kidney transplantation].

PMID- 8159897
TI  - [A case from practice (289). 1. Progression of a moderately differentiated
      prostate carcinoma--initially and at recurrence normal PSA 2. acute postrenal
      kidney insufficiency with anuria and tumor invasion of the lesser pelvis with 3.
      secondary 4-stages deep venous thrombosis on the right; fresh apposition thrombus
      4. status following insertion of a total hip prosthesis on the left in 1985].

PMID- 8159898
TI  - [Reoperations in appendicitis].

PMID- 8159899
TI  - [Solitary rectal ulcer syndrome].

PMID- 8159900
TI  - [Acute appendicitis. A clinicopathological analysis of 200 cases].
AB  - OBJECTIVES: a) to carry out a prospective study of 200 cases of acute
      appendicitis in adult patients; b) to correlate clinical, laboratory,
      radiological, and pathological findings. MATERIAL AND METHODS: clinical data were
      collected from all patients; every patient had hematic biometry, urine exam (UE),
      abdominal radiography, an histopathological study appendix. RESULTS: the patients
      were 98 males and 102 females; 66.5% were between 15 and 25 years old. All
      patients had abdominal pain, 56.5% nausea and vomit, 49% fever, 10.5% diarrhea,
      and 6% urinary symptoms. Post-operatory complications were seen in 24.5%.
      Leucocytosis greater than 10,000 was found in 82.5%, some alteration of UE in
      45%, and abnormal radiography in 56.5%. Histopathological study showed simple
      appendicitis in 16.5%, hemorrhagic in 8%, purulent in 22%, hemo-purulent in
      30.5%, an perforated in 21%. CONCLUSIONS: the diagnosis of appendicitis is
      basically a clinical one, since 17.5% showed normal white-cell count, and 43.5%
      normal radiography.

PMID- 8159901
TI  - [Reoperations in appendicitis].
AB  - We present our experience in reoperations after appendectomy. From 276 patients
      were operated for acute appendicitis, we found 70 who presented appendicular
      abscess, only 13 needed reoperation because of residual abscess, (three cases),
      evisceration (four cases), and cecum perforation (two cases). All had history of
      more than four days of preoperative evolution (range 4-45 days) in those eleven
      patients (six men, and five women) were done 13 reoperations. We had no mortality
      after successful recovery in all of theme. Our experience in reported from the
      surgical services of Hospital General de Mexico an Hospital Juarez, both located
      in Mexico City.

PMID- 8159902
TI  - [Acute acalculous cholecystitis. Results of surgical treatment].
AB  - During an 11 year period, 47 patients with acute acalculous cholecystitis were
      operated on. Two to one male/female ratio was observed with a mean age of 55 age
      of 55 years. No one had a past history of biliary tract pathology but 70 per cent
      of the patients had risk factors, mainly diabetes mellitus, cardiovascular and
      collagenous diseases, some different of those reported in the world literature
      (sepsis, trauma, non biliary tract surgery, etc.). The ultrasound was the best
      diagnostic tool. Open cholecystectomy was performed in all patients and some sort
      of local complication was found in 85 per cent of patients (empyema, gangrene or
      perforation) in spite of the surgical procedure was done on emergency or early
      elective basis, a 31 per cent operative mortality rate was found and a 10.6%
      Operative mortality rates was observed. The bacterial cultures showed gram
      negative and anaerobic flora. This report shows that an early diagnosis and
      surgical treatment keeps a low morbidity and mortality rates but the gallbladder
      late complications have a high rates.

PMID- 8159903
TI  - [Effect of rapeseed from different distributors on the rat liver].
AB  - In previous papers it was reported that rapeseed could prevent the development of
      cirrhosis induced by carbon tetrachloride and at the same time can induce liver
      regeneration in the rat. In such experiments rapeseed was always obtained from
      the same distributor "Semillas Berentsen". When reseed of different distributors
      was used, neither cirrhosis prevention or liver regeneration was observed. The
      difference among the rapeseed used was that "Semillas Berentsen" utilizes a
      fungicide to preserve the seed and the other distributors do not use any
      preservative. This circumstance made think that the active principle responsible
      for the effects observed is probably the fungicide.

PMID- 8159904
TI  - [Solitary rectal ulcer syndrome: report of 7 cases at the Salvador +Zubiran
      National Institute of Nutrition, from 1980 to 1992].
AB  - Solitary rectal ulcer syndrome (SRUS) is an unusual disorder which is seldom seen
      in our hospital. Considerable uncertainly remains concerning the cause, natural
      history, and management of this condition. During 1980-1992 period, 7 patients
      were seen at the Instituto Nacional de la Nutricion and the diagnosis was
      established on histological, sigmoidoscopic and clinical grounds. Most of the
      patients suffered rectal bleeding, abdominal pain, straining at defecation,
      tenemus and rectal mucus discharge. Laboratory results were non specific. Eighty
      five percent has macroscopic ulcerations and these were found within 5.2 cm of
      the anal margin and usually situated anteriorly. Neither medical nor local
      surgical treatment consistently achieved relief of symptoms or healing of the
      lesion.

PMID- 8159905
TI  - [Intestinal pseudo-obstruction. Transendoscopic management].

PMID- 8159906
TI  - [Zenker's diverticulum. Report of 2 cases].
AB  - We review the physiopathology of Zenker diverticulum, its clinic manifestations,
      diagnosis and treatment, we present two cases registered and treated in the
      Hospital General de la Zona No. 1 "Gabriel Mancera" of the Mexican Institute of
      Social Security (IMSS), and compare with the results of other authors,
      emphasizing the utility of the Total Parenteral Nutrition (TPN) in pre and post
      operative period, to improve the nutritional condition and diminish the post
      operative complications and hospital stancy.

PMID- 8159907
TI  - [Laparoscopic surgery of the liver: experimental stage].

PMID- 8159908
TI  - [Surgical treatment of acute pancreatitis. The Mexican experience].
AB  - Acute Pancreatitis is a complex clinical problem. The mexican experience in the
      Acute Pancreatitis treatment was analyzed, from the papers published between 1970
      1990. During the first decades of the 20th century. Acute Pancreatitis was
      usually diagnosed at operation or at autopsy. Because a significant proportion of
      those diagnosed at surgery survived, early intervention was recommended. With the
      introduction of laboratory test, surgical diagnosis was regarded as unnecessary.
      In the past 30 years in has become clear that patients with severe forms of
      Pancreatitis do not survive without surgery and interest in the value of surgical
      measures has been renewed. We reviewed the papers of the surgical treatment of
      Acute Pancreatitis and its complications, only articles with documented surgical
      treatment were selected for analysis. From 1970 through 1990, 41 articles were
      published by Mexican Journals, only 10, fulfill the criteria, 632 patients with
      operative management. Patients with gall-stone associated Pancreatitis were the
      most frequent, 70-72%, and alcoholic Pancreatitis the second 20%; significant
      hospital morbidity occurred, recurrent sepsis was frequently identified;
      mortality rate was 52.6%. Available data do not provide any reasonable approach,
      therefore, we urge to develop clinical trials, with control groups for better
      results.

PMID- 8159909
TI  - Transfer factor and its signification for practice.
AB  - In the study literary data are given together with our own experience with the
      immunomodulation effects of Transfer Factor (TF) Sevac. The application of 3-5
      ampulles of TF leads not only to E rosettes but even to a separate subpopulations
      of T lymphocytes increase. The results obtained in 51 patients with GIT and renal
      cells carcinoma were statistically evaluated. About 80% of the patients
      experienced an improvement of subjective conditions during the treatment.
      Objectively supported adjustment of laboratory indices was found in 83-88% of the
      parameters evaluated. Also the absolute numbers of CD4+ cells in 10(9)/1
      increased (at p < 0.001) together with CD3+ and CD8+ (p < 0.01). A significant
      correlation between separate subpopulations of T lymphocytes and B lymphocytes
      was proved in the original mode. From our results it is obvious that the TF Sevac
      application and further observing of its immunomodulation effect will be the
      object of interest of the immunologists of general practice and clinical research
      even in spite of some lacks in its characteristics.

PMID- 8159910
TI  - Immunoglobulin G subclasses in Crohn's disease with and without bowel resection.
AB  - Increased immunoglobulin G2 [IgG2] in Crohn's disease in contrast with increased
      IgG1 in ulcerative colitis was reported in literature data. The aim of our study
      has been focused on serum IgG subclasses in Crohn's disease with resected bowel
      (11 patients) and without previous surgery for Crohn's disease (12 patients). All
      patients were in active stage of the disease on total parenteral nutrition. Serum
      IgG subclasses were estimated by means of radial immunodiffusion. There was no
      significant differences between in IgG subclasses in Crohn's disease with and
      without bowel resection. IgG2 over 4.5 g/l was found only in 2/12 with resected
      bowel and 1/11 without previous surgery for Crohn's disease. Surprisingly,
      IgG1/IgG2 ratio below 1.5 was found only in 5/23 persons. In 3/23 patients IgG1
      was over 10.5 g/l although there was no doubt about the diagnosis of Crohn's
      disease. IgG subclasses failed to help in confirmation of the diagnosis of
      Crohn's disease. Serum IgG subclasses alterations probably are not influenced by
      bowel resection and/or nutritional status.

PMID- 8159911
TI  - Neopterin in the diagnosis of disorders associated with immune system activation.
AB  - While the knowledge concerning the role of the immune system in many internal
      disorders has grown rapidly in recent years, there are few methods to assess
      immune system activation in clinical practice. Measurement of urine neopterin,
      product of a metabolic pathway controlled by interferon-gamma, has been found
      useful in many clinical conditions. The present study concerns neopterin
      excretion in 157 patients with different internal disorders. As expected, we
      found an increase in urine neopterin in patients with malignant tumors,
      autoimmune disorders like systemic lupus erythematosus or inflammatory bowel
      disease, and infections. Elevated neopterin levels were also observed in acute
      pancreatitis and in acute myocardial infarction. In addition, significant
      correlations between urine neopterin and zinc and neopterin and copper excretion
      were found suggesting a physiological role of neopterin as urine antioxidant.

PMID- 8159912
TI  - Application of digital image processing to evaluation of eye fundus pictures.
      Preliminary report.
AB  - An application of computerized digital analysis to photographically recorded
      pictures of the fundus of the eye is described. This approach has been found as a
      reproducible and objective method for detection and description of different
      changes in ocular tissues (exudative diabetic maculopathy especially) for the
      diagnostic or prognostic purposes (progress of the illness, results of the
      treatment). Possibilities offered by this method in other relevant retrospective
      studies are also discussed.

PMID- 8159913
TI  - Tumorous thrombosis of the vena cava inferior--experience with surgical
      treatment.
AB  - Patients suffering from renal carcinoma, treated at the Department of Urology in
      Hradec Kralove, have been systematically followed up since 1962. In the present
      study we evaluated a group of patients treated from the year 1985 till 1991. The
      group consisted of 365 patients with renal carcinoma. In 55 (15%) of them
      invasion into the renal vein or into the vena cava inferior was found (in 43 men
      and 12 women). In 38 patients the tumour with thrombus in the vena cava inferior
      was on the right side, in 17 the tumour of the left kidney was removed. The
      proportion of the right side to the left was 2.2:1. The surgical treatment of
      tumorous thrombosis depends on the upper border line of the tumorous thrombus.
      The tumorous thrombus in the subhepatic segment of the vena cava inferior can be
      treated by its massaging into the renal vein after the obliteration of the artery
      or by the parietal resection of the vena cava inferior. The resection of the vena
      cava inferior was performed in 32 patients. In 5 patients the tumorous invasion
      could not be treated because of extensive metastases (into the liver and the
      lung) or there was a tumorous parietal infiltration of the vena cava inferior.
      Evaluating the whole group after 30 years inclusive of the Navratil's set made
      with our cooperation, there were 1,005 patients suffering from renal tumours,
      operated on at the Department of Urology in Hradec Kralove. In 155 (15.4%)
      tumorous thrombi were surgically removed from the great veins. In 38 cases there
      was a demarcation of tumorous thrombi to the renal vein but in 117 the thrombus
      penetrated into the vena cava inferior.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8159914
TI  - Endotoxin-induced acute tubular necrosis in cirrhotic rats.
AB  - In order to clarify the role of endotoxin in acute tubular necrosis in liver
      cirrhosis, lipopolysaccharide (LPS) was injected to rats with liver injury with
      exposure to carbon tetrachloride (CCl4) inhalation. Rats showed liver cirrhosis
      with ascites retention after 10 weeks' CCl4 treatment and liver fibrosis after 6
      weeks' CCl4 treatment. Histopathological grading of kidney injuries after LPS
      treatment was more severe either in cirrhotic rats or in liver fibrotic rats than
      in normal rats. All cirrhotic rats had severe acute tubular necrosis after either
      dose of LPS, but only small necrotic foci of tubuli were seen in a few normal and
      liver fibrotic rats. The results indicate that endotoxin, which overflows due to
      disturbance of inactivation in the cirrhotic liver, may contribute to acute
      tubular necrosis. This effect of endotoxin is supposed to be a direct hemodynamic
      damage.

PMID- 8159915
TI  - Protein intake and glomerular hyperfiltration in insulin--treated diabetics
      without manifest nephropathy.
AB  - Protein intake in relation to glomerular filtration rate (GFR) and urinary
      albumin excretion (UAE) has been studied in 96 insulin-treated diabetic patients,
      20-40 years of age and without nephropathy. They had diastolic blood pressure
      (DBP) not exceeding 90 mmHg and a GFR exceeding -2 SD of the age-related value.
      They were without medications except for insulin. There were no significant
      differences in protein intake between diabetic patients with and without
      hyperfiltration (1.18 +/- 0.26 g/kg/d vs 1.21 +/- 0.42 g/kg/d, p = 0.75) or
      between diabetic patients with or without increased UAE (1.16 +/- 0.41 g/kg/d vs
      1.24 +/- 0.37 g/kg/d, p = 0.37). No relations were found between protein intake
      and GFR or UAE in the whole sample, but a positive relation was found between UAE
      and protein intake in patients with increased UAE. Protein intake correlated with
      UAE in hyperfiltrators who use tobacco (n = 8, r = 0.85, p = 0.01), but not in
      non-users (n = 11, r = 0.24, p = 0.48). In conclusion our findings give no
      support for a relation between high protein intake and glomerular hyperfiltration
      in insulin-treated-diabetic patients. However, in contrast to non-users of
      tobacco, a positive relation was found between UAE and protein intake in tobacco
      users with hyperfiltration.

PMID- 8159916
TI  - Treatment of hypercalcaemia with pamidronate in patients with end stage renal
      failure.
AB  - Pamidronate was given to 10 patients with end stage renal failure who had become
      symptomatically hypercalcaemic due to the use of calcium based phosphate binders
      and alphacalcidol. All patients were initially treated with rehydration,
      increased dialysis and withdrawal of drugs, however despite this they remained
      symptomatic and the serum calcium remained elevated, mean 3.89 mmol/l (range 3.44
      4.74). Pamidronate was given, and the serum calcium had declined to 2.92 mmol/l
      (2.79-3.84), p < 0.01 by the third day. The reduction in serum calcium observed
      with pamidronate was more rapid than that in 9 patients who developed
      asymptomatic hypercalcaemia, mean serum calcium 3.45 mmol/l (3.4-3.56), with an
      actual median reduction of 0.72 mmol/l (0.37-1.30) in the pamidronate group after
      3 days compared to 0.20 mmol/l (0.10-0.52) in the conservatively treated
      asymptomatic group, p < 0.01, and a median percentage decrease of 19% (10-30) in
      the pamidronate group and 6% (3-15) in the asymptomatic group, p < 0.01. In this
      study pamidronate was a safe and effective agent in reducing serum calcium in a
      group of hypercalcaemic dialysis patients.

PMID- 8159917
TI  - Short and long term outcome in a consecutive series of 419 patients with acute
      dialysis-requiring renal failure.
AB  - This analysis was done in a consecutive series of 419 patients with potentially
      reversible acute renal failure (ARF) requiring dialysis treated during the 12
      year period January 1977 to December 1988. The aims were to describe the
      relationship between morbidity, mortality, and the year of admission, to evaluate
      the effects of various follow-up periods and stratification on main prognostic
      factors, and to report long term survival. RESULTS: 1) There was a significantly
      higher (p < 0.001) number of organ failures/patient in the last 6 year period
      compared with the first 6 year period. 2) Early (day 90) mortality was 46% and
      did not change significantly during the 12 year period. 3) Etiology, age of the
      patient, and the severity and the progression of the underlying disease were the
      most important factors determining outcome. 4) Time of censorship and
      stratification of the patients influenced prediction models. 5) Estimated 5 year
      survival rate was 52% (95% confidence limits 44-60%) in patients with a medical
      etiology, and 28% (95% confidence limits 20-36%) in patients with a surgical
      etiology. CONCLUSIONS: 1) Prognosis did not change significantly during the 12
      year study period, and was almost solely dependent on the severity and
      progression of the underlying disease process. 2) Changed censoring time and
      stratification were important tools for enhancing the yield of information from
      the study. 3) The time(s) and method(s) of risk scoring, stratification(s) of
      patients, the time(s) of censorship on vital status, and the method for
      statistical analysis have to be identical if results of treatment for ARF from
      different centers should be compared.

PMID- 8159918
TI  - Absorption of irrigating fluid during percutaneous transrenal lithotripsy.
AB  - Twenty-eight patients who underwent percutaneous lithotripsy with isotonic
      mannitol solution as the irrigating fluid were studied. Intraoperative
      intravenous and total absorption of irrigating fluid was estimated from
      postoperative analyses of plasma and urinary concentrations of mannitol. Most
      operating times were short and only minor fluid absorption was recorded. In six
      cases, however, the fluid absorption exceeded 100 ml and two of these had a
      maximal calculated absorption of more than 1000 ml (1220 and 1860 ml,
      respectively). Intraoperative bleeding was a warning sign of absorption of
      irrigating fluid.

PMID- 8159919
TI  - "In situ" echo-guided extracorporeal shock wave lithotripsy of ureteral stones.
      Methods and results with Dornier MPL 9000.
AB  - In 285 patients with prevesical ureteral stone and 247 with upper ureteral stone,
      extracorporeal shock wave lithotripsy (ESWL) was performed with the Dornier MPL
      9000 ultrasonographic targeting device. All these stones were treated "in situ"
      and without regional or general anaesthesia. At 3-month follow-up 96.8% of the
      patients treated for prevesical stone and 95.5% of those with upper ureteral
      stone were stone-free. ESWL was repeated once or twice in 99 cases; the average
      number of sessions was 1.2 for all patients (similar for prevesical and upper
      ureteral stones). Sparse use of ureteral stenting (6.2% of cases) did not seem to
      reduce the efficacy of ESWL or increase complications or need for retreatment.
      Intravenous fentanyl analgesia was given to 40.9% of the patients and intravenous
      infusion of a furosemide solution was employed in many cases to give adequate
      dilation of the urinary tract. In situ echo-guided ureteral ESWL is simple, safe
      and efficacious and can be the technique of choice for sonographically detectable
      ureteral stone.

PMID- 8159920
TI  - The effects of orchidectomy on skeletal metabolism in metastatic prostate cancer.
AB  - The skeletal metabolic effects of androgen withdrawal have been studied in men
      with metastatic prostate cancer by using a combination of sequential biochemical
      measurement, quantitative and subjective bone histology and selective osteoclast
      inhibition with the bisphosphonate Pamidronate. Results showed dissociation in
      the levels of biochemical markers of bone formation (alkaline phosphatase and
      osteocalcin) following castration, whilst markers of bone breakdown (urinary
      hydroxyproline creatinine (OHP) and calcium excretion (CaE)) increased in the
      majority of patients. The osteolytic response was inhibited by the bisphosphonate
      Pamidronate (Aminohydroxypropylidene Bisphosphonate (APD)), thus confirming its
      osteoclastic origin. Histomorphometry of tumour free bone showed an acute drop in
      bone volume following surgery (p < 0.05). This effect was blocked by Pamidronate
      suggesting that osteoclastic activity surges immediately following castration,
      contributing to the acute bone loss. Histology of metastatic areas showed a
      marked diminution in bone volume due to decreased osteoblast activity and
      markedly increased osteoclast mediated osteolysis. In 56% of biopsies there were
      residual foci of active tumour within metastatic areas after orchidectomy. These
      disturbed metabolic bone activity in a typically localised manner.

PMID- 8159921
TI  - Neodymium-YAG laser treatment in localized prostatic cancer. High rate of local
      failure.
AB  - Clinically localized prostatic cancer, T0-2,NX,M0, was treated with extended
      transurethral resection and subsequent neodymium-YAG laser irradiation of the
      prostatic cavity in 20 patients in 1987-1990. The patients' mean age was 71
      (range 64-84) years. During 12-month follow-up only three patients had negative
      biopsies, whereas 16 had residual cancer and one had atypical, suspectedly
      malignant cells. Eight of the 16 with residual cancer underwent repetition of the
      combined resection and laser treatment, but this led to negative biopsies in only
      two cases. The treatment per se was well tolerated and side effects were few, but
      the poor outcome concerning local tumor control is contradictory to previous
      reports and raises doubts as to the advisability of offering such treatment as an
      alternative to radical prostatectomy.

PMID- 8159922
TI  - Blood loss during transurethral resection of the prostate as measured by the
      HemoCue photometer.
AB  - Blood loss was measured with the portable HemoCue photometer and the absorption
      of irrigating fluid was assessed by the ethanol method during 700 transurethral
      resections of the prostate. The blood loss ranged between 10 and 3,825 ml (median
      300 ml). The weight of the resected prostatic tissue and the operating time were
      independent predictors of the amount of blood lost. General anaesthesia (n = 82)
      and malignant histology (n = 114) were associated with a smaller blood loss. In
      the patients who were given regional anaesthesia (n = 618), an mean systolic
      blood pressure of 100 mmHg or less resulted in a smaller bleed. Large-scale
      irrigating fluid absorption was typically associated with a blood loss of medium
      size and ranged between 500 and 1,000 ml. The incidence of such absorption was
      negligible in the patients in whom the blood loss per gram of resectate was less
      than 10 ml/g. Blood loss was also measured every 10 min during the course of
      another 110 operations, from which 20 patients with operating times in excess of
      60 min were selected. Our analysis showed that no excessive blood loss occurred
      after 60 min of surgery.

PMID- 8159923
TI  - Young-Dees-Leadbetter bladder neck reconstruction for sphincteric urinary
      incontinence: the value of augmentation cystoplasty.
AB  - Young-Dees-Leadbetter bladder neck reconstruction was performed in five females
      and two males with bladder exstrophy, two females and one male with epispadias,
      and two females with congenital short urethra. Eight patients had simultaneous
      augmentation colocystoplasty (7 exstrophy, 1 female epispadias), seven of whom
      are continent for three hours or more. Two patients void spontaneously and five
      are managed by clean intermittent catheterization (CIC) with which there were
      considerable problems in the beginning. Three of the four patients in whom
      simultaneous bladder augmentation was not undertaken remained incontinent because
      of small hypocompliant bladders. One has had a secondary augmentation cystoplasty
      and two may need it. Young-Dees-Leadbetter bladder neck reconstruction is a
      satisfactory operation for sphincteric urinary incontinence despite problems with
      CIC. However, bladder capacity may be considerably reduced after reconstruction.
      Augmentation cystoplasty should be considered not only in exstrophy patients
      undergoing bladder neck reconstruction but also in patients with other
      abnormalities.

PMID- 8159924
TI  - The effect of pharmacological stimulation and blockade of autonomic receptors on
      the urethral pressure and power generation during coughing and squeezing of the
      pelvic floor in healthy females.
AB  - The effect of autonomic receptor agonists and antagonists on the urethral
      pressure and power generation during coughing and squeezing of the pelvic floor
      has been evaluated in 30 healthy females. The measurements were carried out at
      the bladder neck, in the high pressure zone, and distally in the urethra. The
      used drugs (noradrenaline, prazosin, terbutaline, propranolol, carbachol and
      atropine) caused no significant change in the pressure and power generation. The
      clinically relevant influence of drugs on the urethral closure function should be
      re-appraised when based on profilometry in the resting state. The results support
      that the effect of the autonomic nervous system on the urethral closure function
      is insignificant in healthy women. They furthermore indicate that investigations
      on the ability to secure continence cannot be based solely on resting pressure
      profilometry, but should be accomplished by measurements during stress episodes.

PMID- 8159925
TI  - Left-sided laparoscopic adrenalectomy.
AB  - Laparoscopic transperitoneal adrenalectomy was performed in a 42-year-old female
      with a left adrenocortical adenoma causing Conn's syndrome. No technical problems
      occurred during surgery and the patient recovered quickly.

PMID- 8159926
TI  - Multifocal renal cell carcinoma of collecting duct origin.
AB  - In kidney tumors arising from the collecting duct epithelium (Bellini duct
      carcinoma), histologic examination shows both tubular and papillary architecture,
      which can lead to misinterpretation as renal cell or transitional cell carcinoma.
      A case of multifocal bellini duct carcinoma is described, to the authors'
      knowledge the first to be reported.

PMID- 8159927
TI  - Ureteral obstruction due to primary localized amyloidosis.
AB  - Localized amyloidosis of the ureter is a rare condition. There are only 27 cases
      reported. Because of the difficulty in differentiating between localized
      amyloidosis or other benign conditions and a malignant tumor many cases have led
      to nephroureterectomy. We report a case of a middle aged woman who had an almost
      complete obstruction of the right ureter caused by amyloidosis. Biopsies were
      taken via a ureteroscope prior to exploration of the ureter enabling the patient
      to be treated with local excision and ureteroneocystostomy instead of
      nephroureterectomy.

PMID- 8159928
TI  - Salvage of difficult transplant urinary fistulae by ileal substitution of the
      ureter.
AB  - We report our experience with 4 cases of ileal substitution of the ureter after
      live-donor kidney transplantation and review the literature. The indications were
      recurrent ureteric fistula and obstruction in 3 cases and extensive necrosis of
      the ureter and renal pelvis in one case. Nephrostomy tube drainage was a useful
      adjunct to diagnosis and treatment of the 4 cases. No mortalities or graft losses
      were encountered and satisfactory graft function was maintained 2-14 years after
      ileal substitution of the ureter. Moreover, no electrolyte or acid-base
      disturbances were observed. One patient developed recurrent vesical stones 2 and
      4 years after ileoureteral replacement secondary to bladder neck obstruction.
      Ileal substitution of the ureter seems a feasible operation to salvage difficult
      and recurrent transplant urinary fistulae in exceptional situations when it is
      impossible to restore urinary continuity using urinary tract tissues.

PMID- 8159929
TI  - Calculi in a blind-ending limb of a duplicated ureter.
AB  - An unusual case with a blind-ending ureteral duplication containing stones is
      reported. A patient who had undergone two consequent unsuccessful operations
      attempted to extract a lower ureteral stone was later found to have the missing
      stone in the blind-ending branch of a duplicated ureter. The clinical
      significance of such malformation is discussed in light of the literature.

PMID- 8159930
TI  - Acute urinary retention in two patients with imperforate hymen.
AB  - Acute urinary retention in two adolescent girls with hematometrocolpos caused by
      imperforate hymen are reported. The accumulation of the menstrual blood in the
      vagina and uterus may form a mechanical effect on the urethra and bladder and
      lead to the obstructive urinary symptoms. Hymenotomy created individually by CO2
      laser and cruciate incision was performed. The two patients were discharged on
      the same day after operation and made an uneventful recovery.

PMID- 8159931
TI  - Local fibrinolysis and perfusion in the treatment of priapism of the corpora
      cavernosa and corpus spongiosum.
AB  - A 69-year-old patient was referred with priapism of the corpora cavernosa and the
      corpus spongiosum. Blood aspiration, irrigation with heparin-saline solution and
      metaraminol injections proved unsuccessful. Surgical intervention was inadvisable
      in view of delayed coagulation. Complete detumescence was achieved after
      intracorporeal perfusion with streptokinase.

PMID- 8159932
TI  - Granuloma annulare localized to the shaft of the penis.
AB  - A case of granuloma annulare localized to the shaft of the penis is reported. The
      differential diagnoses are discussed. Penile granuloma annulare is a rare
      disorder and it is concluded that biopsies of penile lesions are recommended to
      verify the correct diagnosis.

PMID- 8159933
TI  - Epididymal metastasis from prostatic carcinoma.
AB  - Epididymal metastasis from prostatic carcinoma is rare. A case mimicking
      cystadenocarcinoma of the epididymis is presented and the literature is reviewed.
      Investigation for prostate-specific antigen should always be done in carcinoma of
      the epididymis, and when subcapsular orchidectomy is performed the epididymis
      should be carefully examined.

PMID- 8159934
TI  - Testicular malacoplakia.
AB  - Testicular malacoplakia presenting as painless enlargement of the testis in a 23
      year-old man is described. The literature is reviewed.

PMID- 8159935
TI  - Synchronous bilateral seminoma testis treated with unilateral orchiectomy and
      contralateral irradiation: a therapeutic option.
AB  - In the past 20 years, 14 cases of simultaneous bilateral seminoma testis treated
      with bilateral orchiectomy and adjuvant radiotherapy have been reported in the
      literature. A case is now described in which treatment consisted of unilateral
      orchiectomy, with radiotherapy to the contralateral tumor and the lymph nodes.

PMID- 8159936
TI  - Silicone mammary implants and connective tissue disease.
AB  - The American Food and Drug Administration recently restricted the use of silicone
      gel-filled mammary implants for breast augmentations and reconstructions because
      a number of case reports had suggested that there was an association between
      silicone and connective tissue disease. We have found 36 such case reports
      published since 1982. Systemic sclerosis is the most common reported diagnosis (n
      = 15). Implants were removed from 15 patients, in nine of whom symptoms improved.
      The mechanism behind the postulated relationship is obscure, and most authors
      focused on an auto-immune-like response to silicone, which acts directly as a
      hapten or as an adjuvant. We found no conclusive evidence to implicate silicone
      mammary implants in connective tissue diseases. We do, however, recommend removal
      of implants from patients with severe connective tissue diseases. Patients with
      symptoms or active connective tissue disease should not be considered for
      silicone implants.

PMID- 8159937
TI  - Impaired sensory conduction in a mixed nerve induced by high frequency
      stimulation of the muscle fibres. An experimental study in cats.
AB  - To see if symptoms such as sensory disturbance or numbness worsen during exercise
      as is thought to occur in entrapment neuropathy, we studied the interaction
      between sensory and muscle nerve fibres in a mixed nerve in cats. Stimulation
      electrodes were placed on both the deep (muscle) and superficial (sensory) branch
      of the radial nerve at the elbow. High frequency stimulation at 100 Hz was
      applied to one branch for five minutes and the nerve action potential of the
      other branch was recorded at the axilla where the radial nerve is mixed. The
      stimulation decreased the amplitude of the nerve action potential and prolonged
      its latency. Recovery from these changes was gradual, and changes were the same
      whichever branch was stimulated. When a cat's leg was made ischaemic, the changes
      were more pronounced. The changes in the nerve action potential may have arisen
      from ischaemia in the nerve, possibly caused by high frequency stimulation.

PMID- 8159938
TI  - Fibrin glue (Tisseel) added with sodium hyaluronate in microvascular
      anastomosing.
AB  - To test the effect on the handling properties of a two component fibrin glue, the
      viscosity was increased with sodium hyaluronate and the glue was applied to a
      microvascular anastomosis in rats. The femoral artery of each rat was anastomosed
      with three conventional sutures and then sealed with fibrin glue. Three glues
      with different viscosities were tested: original Tisseel fibrin glue (Immuno AG,
      Vienna); Tisseel with 0.9% sodium chloride added to the fibrinogen component; and
      Tisseel with a high molecular weight sodium hyaluronate (10 mg/ml, Healon,
      Pharmacia, Sweden) added to the fibrinogen component. The increased viscosity of
      the fibrin glue to which hyaluronate had been added resulted in a significantly
      higher patency rate 20 minutes after completion of the anastomosis (p < 0.01),
      and reduced the amount of fibrin that entered the vessels.

PMID- 8159939
TI  - Gap formation after flexor tendon repair in zone II. Results with a new
      controlled motion programme.
AB  - Intratendinous metal markers were used to study gap formation in 36 flexor
      digitorum profundus repairs during and after early controlled motion with a
      programme combining dynamic traction and passive flexion to all four digits. The
      mean gap 3 weeks after operation was 2.5 mm. The mean final gap was 2.6 mm. The
      results of linear regression analysis showed that gap formation within the
      observed range from 0 to 8.5 mm did not negatively affect tendon excursions or
      clinical results in terms of active interphalangeal joint range of motion. These
      findings are in accordance with the results of a previous study of gap formation
      in patients treated with a modified traditional Kleinert traction programme.
      Together the two studies confirm that controlled motion is effective in
      restricting the adhesions associated with gap formation during postoperative
      immobilisation.

PMID- 8159940
TI  - Involvement of connections between the brainstem and the sympathetic ganglia in
      the pathogenesis of rheumatoid arthritis. An anatomical study in rats.
AB  - The central connections between the superior cervical ganglion of the sympathetic
      trunk and the brainstem were investigated in five rats by trans-synaptic
      transport of lectin-conjugated horse-radish peroxidase. After injection of this
      tracer into the superior cervical ganglion, labelled cells were seen in both the
      ventral and dorsal parts of the medullary reticular formation. The neurons were
      found mainly on the same side as the injection site. Besides retrograde
      labelling, there was an antegrade termination within the nucleus of the solitary
      tract. We hypothesise that a nervous mechanism is involved in the pathogenesis of
      rheumatoid arthritis, and that a supraspinal input to the sympathetic ganglia
      might influence this mechanism.

PMID- 8159941
TI  - A multicentre comparison of treatment regimens for unilateral cleft lip and
      palate using a multiple regression model.
AB  - The European Cleft Lip and Palate Research Group consists of specialists in
      orthodontics from six centres for the treatment of cleft palate in northern
      Europe. The purpose of this part of the multicentre study was to investigate
      whether differences in outcomes could be explained by specific treatment
      regimens. Three regimens that were assumed to influence the outcome of treatment
      were selected: Presurgical orthopaedics, closure of the palate, and primary bone
      grafting. The sample comprised 151 children with complete unilateral cleft lip
      and palate from the six centres. The result of multiple regression analysis
      showed that within that sample it was not possible to reach definite conclusions
      as to which factors exerted the most favourable influence on facial growth, but
      primary bone grafting was associated with reduced maxillary inclination and
      presurgical orthopedics with increased mandibular inclination.

PMID- 8159942
TI  - Sizes of dental arches in children with the Pierre Robin syndrome and isolated
      cleft palate aged from 0.2 to six years.
AB  - Development of the dental arches and length and weight at birth were studied from
      0.2 to 6 years of age in 78 children with Pierre Robin syndrome and 58 with
      isolated cleft palate. The growth of the maxillary dental arches was similar in
      both groups before palatal closure. The anterior width of the maxillary arch did
      not differ between the groups during the six year follow up period, but the
      depths of the maxillary and mandibular arches were significantly less (< 0.001)
      in the group with Pierre Robin syndrome compared with those with isolated cleft
      palates at the age of 3 and 6 years. The mandibular width at the first and second
      deciduous molars in the group with Pierre Robin syndrome was also significantly
      smaller (< 0.01) than in the other group at the age of 6 years. The weight and
      length at birth were similar in both groups, and they were slightly lower than
      among the normal Finnish population.

PMID- 8159943
TI  - Surgical treatment of cleft palate. 27 years' experience of the Wardill-Kilner
      technique.
AB  - During the period 1958-1985, 230 patients with cleft palate were operated on in
      the Department of Plastic Surgery, University of Goteborg, Sweden. A modified
      push-back technique according to Wardill and Kilner was used. The children were
      operated on at a mean age of 13 months. They were divided into two groups, the
      first in which the cleft affected the velum only (n = 121) and the other in which
      it also affected the hard palate (n = 109). Postoperative dehiscences and
      fistulas occurred in 19 (8%) patients, of which 16 (15%) belonged to the group in
      which the cleft affected the hard palate. Only three (2%) of the 121 patients
      with a cleft in the soft palate only developed dehiscences. The total number of
      patients who had to be reoperated on because of dehiscences were 10 (4%) and
      palatopharyngeal flaps had to be performed in 25 patients (11%) because of speech
      problems.

PMID- 8159944
TI  - Maxillary dental arch and occlusion in patients with repaired clefts of the
      secondary palate. Influence of push back palatal surgery.
AB  - Maxillary morphology and dental occlusion were studied from infancy to age 10
      years in 32 patients born with isolated cleft palate. Wardill-Kilner push back
      repair of the palate had been done at a mean age of 7.5 months. Measurements
      obtained from casts of the jaws showed that the average maxillary dimensions
      before as well as after operation were less than those reported for children
      without clefts. The mean reduction was similar whether the cleft reached into the
      hard palate or affected the soft palate only. Preoperative anterior maxillary
      arch width in particular, and also distance from scar line to selected teeth
      seemed to influence postoperative development of the maxillary dental arch in
      individual patients.

PMID- 8159945
TI  - Assessment of speech in children after repair of isolated cleft palate.
AB  - The speech of 31 consecutive patients with isolated cleft palate was evaluated
      when they were between 10 and 14 years of age. All the children had Wardill
      Kilner push-back repairs at a mean age of 7.9 months. Several speech variables
      were assessed by two trained listeners. In addition, an overall evaluation of the
      quality of the patients' speech was made by the listeners and by the patients
      themselves. The patients had some remaining speech problems, mainly hypernasality
      which was moderate or severe in 7 (23%). The prevalence of compensatory
      articulations was low, however (n = 4, 13%), and most patients thought that their
      own speech was normal or relatively normal.

PMID- 8159946
TI  - Giant ventral hernias and their repair. A 10 year follow up study.
AB  - A consecutive series of 32 repairs of massive incisional hernias have been
      followed up for a median of 45 months (range 8 months to 11 years). The
      reconstruction was based on the frontal leaf of the rectus abdominis and
      insertion of free fascia or pedicle flap from the tensor fascia lata muscle
      combined with transposition of the rectus muscle. Median size of the hernias was
      20 x 17 cm (range 6-35 x 8-30). The incidence of risk factors for both recurrence
      as well as operative complications was high. During the median observation period
      of 45 months 9 hernias recurred, the main benefit of a successful reconstruction
      was relief of pain in the abdominal wall and the lower back. We conclude that the
      method is useful for the treatment of patients with large ventral hernias.
      Reduction of controllable recurrence risk factors is important, and the treatment
      requires substantial resources and expertise.

PMID- 8159947
TI  - Fractures of the hand. Distribution and relative incidence.
AB  - One thousand consecutive fractures of the metacarpals, phalanges, and carpal
      bones have been recorded over a period of about 10 months in Bergen, Norway, to
      find out the relative incidence of these fractures in an unselected series: this
      corresponds well with the few other reports of the incidence of hand fractures
      that we could find. In the total series the metacarpals, phalanges, and carpal
      bones account for 36%, 46%, and 18% of the fractures, respectively. Fractures of
      the scaphoid make up 10.6% of the total, fractures of the neck of the fifth
      metacarpal 9.7%, and Bennett's fractures 1.4%. The outer areas of the hand are
      most commonly damaged,--the fifth ray, the thumb ray, and the distal phalanx of
      the third finger account for half of all fractures of the hand.

PMID- 8159948
TI  - Post-traumatic partial rupture of the extensor carpi ulnaris tendon. Case report.
AB  - A 40 year old man presented with continued pain, tenderness and slight swelling
      on the ulnar aspect of his right wrist after handling a heavy object. At
      operation, partial rupture of the extensor carpi ulnaris tendon was diagnosed and
      successfully treated by suture of the tendon. Partial rupture of the extensor
      carpi ulnaris tendon may be more frequent than previously reported, and the
      diagnosis should be considered in patients with symptoms of post-traumatic
      synovitis of the tendon.

PMID- 8159949
TI  - An extraperitoneal ischiorectogluteal lipoma treated by liposuction. Case report.

PMID- 8159950
TI  - Fibroadenoma associated with gynaecomastia in an adult man. Case report.
AB  - A 40-year-old man was operated on for gynaecomastia, and on histological
      examination the enlarged breast tissue was found to contain a fibroadenoma.
      Fibroadenoma of the breast is extremely rare in men, and this is the first report
      to our knowledge of a fibroadenoma associated with idiopathic gynaecomastia.

PMID- 8159951
TI  - Biological monitoring, carcinogenicity and risk assessment of trace elements.

PMID- 8159952
TI  - Cancer risks for humans from exposure to the semiconductor metals.
AB  - Of the semiconductor metals, only arsenic has been extensively studied as a human
      carcinogen and systemic toxicant. Recent studies have shown, however, that
      gallium, arsenic, and indium are capable of producing marked alterations in
      cellular gene products. After acute in vivo administration indium and thallium
      have been shown to produce decreases in the activity of some drug-metabolizing
      enzymes dependent on cytochrome P-450; therefore these metals would be capable of
      interfering with the metabolism of organic carcinogens. Selenium is essential for
      the activity of the enzyme glutathione peroxidase, which modulates the active
      intermediates generated by drug-metabolizing enzyme systems. Germanium produces
      toxicity in a number of organ systems. Antimony produces lung and circulatory
      system effects. Overall, available data suggest that these metals or metalloids
      are capable of biologically altering several cellular defense mechanisms involved
      in the carcinogenic process and that further studies are needed to determine the
      associated risks.

PMID- 8159953
TI  - Cadmium carcinogenesis and its relationship to other health effects in humans.
AB  - Several different adverse health effects can be caused by cadmium exposure to
      humans and animals. In environmental and occupational health it is important to
      identify effects that occur at relatively low exposures (ie., the critical
      effects that are crucial for preventive action). In long-term human exposures to
      cadmium, effects of cadmium on the kidney have been considered to be critical
      effects and quantitative risk assessments of these effects have been performed on
      the basis of both risk modeling and direct epidemiologic observation. However,
      experimental and epidemiologic studies are providing increasing evidence that
      cadmium is carcinogenic, and this effect, which is considered to be stochastic in
      character, can be considered to be the critical effect. A quantitative evaluation
      of the cancer risk is currently difficult to make, but the preventive action
      against such effects is usually to limit the exposure as much as possible.

PMID- 8159954
TI  - Excess cancer incidence among workers exposed to fluoride.

PMID- 8159955
TI  - Carcinogenicity of trace elements. Report of a panel discussion in Stockholm 25
      May 1992.

PMID- 8159956
TI  - Risk assessment of essential elements.

PMID- 8159957
TI  - Risk assessment of essential trace elements--considerations from the Swedish
      National Food Administration.

PMID- 8159958
TI  - Reference dose of the United States Environmental Protection Agency.

PMID- 8159959
TI  - Essentiality and toxicity of selenium with respect to recommended dietary
      allowances and reference doses.

PMID- 8159960
TI  - Risk assessment of selenium.

PMID- 8159961
TI  - Chromium as an essential and toxic metal.

PMID- 8159962
TI  - Toxicity versus essentiality of chromium.

PMID- 8159963
TI  - Zinc requirements, the recommended dietary allowance and the reference dose.
AB  - 1. The 1989 zinc RDA is not congruent with many of the estimates of requirements
      determined by factorial or metabolic methods. 2. The proposed zinc RfD was based
      on the finding of lower activity of E-SOD after the administration of zinc in a
      form that might be consumed in an unprescribed medication. This lower activity
      was taken as a marker of toxicity. 3. The proposed zinc RfD is incompatible with
      the 1989 RDA and the 1973 WHO FER or requirements published by King & Turnland
      (23). 4. A calculation of the RfD that accounts for bioavailability gives RfD
      values for OTC medications, and high and low bioavailability diets of 0.25, 0.83
      and 1.66 mg.kg-1.d-1, respectively.

PMID- 8159964
TI  - Zinc and the stress response.

PMID- 8159965
TI  - Essentiality and toxicity of zinc.

PMID- 8159966
TI  - Determination of the possible requirement and reference dose levels for arsenic
      in humans.

PMID- 8159967
TI  - Recommendations of the International Union of Pure and Applied Chemistry
      concerning analytical quality criteria in the biological monitoring of toxic
      metals.
AB  - A working party of the Commission of Toxicology of the International Union of
      Pure and Applied Chemistry has been set up to establish criteria to ensure
      analytical quality in the biological monitoring of toxic metals. Although the
      project has not yet been completed, some useful guidelines have been produced.
      They pertain to the description of the subject (so as to allow classification
      into a given "reference group"), the collection, storage and sampling of body
      fluids for trace-element determinations, and criteria to ensure the application
      of the correct analytical procedure, together with a quality-assurance protocol.
      It was agreed that a dedicated sampling protocol is required for each trace
      element in a particular matrix. Although it is impossible to specify this
      protocol together with all subsequent procedures in precise detail, the members
      of the working party have laid down general rules to be followed. This paper
      summarizes what has been achieved to date.

PMID- 8159968
TI  - International project for producing reference values for concentrations of trace
      elements in human blood and urine--TRACY.
AB  - In assessing the concentrations of toxic metals, such as cadmium, chromium, and
      mercury, in human blood and urine samples to determine whether they are abnormal
      or not, reliable reference values are needed from populations of
      nonoccupationally exposed subjects. Numerous publications present concentrations
      claimed to be typical for the study populations, but they can differ by up to an
      order of magnitude for a particular element. This is the consequence of general
      problems that are related to the definition of the reference groups, and the
      sampling and analytical procedures used, and that make it difficult to define
      typical and unbiased values. An international group of experts now establishes
      criteria and procedures to evaluate publications containing information on the
      concentrations of metals in tissues and body fluids for reference populations.
      These evaluations have been compiled in a data base (TRACY).

PMID- 8159969
TI  - Biological monitoring of cadmium exposure--an Italian experience.
AB  - Studies carried out over the last 12 years in northern Italy on a case list of
      105 cadmium (Cd) workers showed that blood levels (B-Cd) were influenced not only
      by current exposure but also by body burden, while urinary levels (U-Cd) were
      influenced predominantly by body burden. Moreover, no advantages were gained by
      adjusting U-Cd for creatinine or specific gravity. The urinary beta 2
      microglobulin levels were within the reference values when B-Cd and U-Cd were
      below the current threshold values. However, some indicators of early renal
      effect appeared to be altered. An increase in chromosome-type aberrations in
      lymphocytes occurred in workers with a heavy cadmium burden. Studies carried out
      on more than 600 subjects from the general population showed higher B-Cd levels
      in smokers than in nonsmokers. B-Cd levels were higher in men and in higher age
      groups. Identifying reference values for B-Cd through meta-analysis studies seems
      useful.

PMID- 8159970
TI  - Biological monitoring of nickel in humans.
AB  - The literature since 1985 on the biological monitoring of occupational,
      environmental, or iatrogenic exposures of humans to nickel is surveyed from the
      author's perspective. Urine and serum are the body fluids commonly analyzed for
      nickel. Nickel concentrations in urine specimens from unexposed persons usually
      exceed the current analytical detection limits, while nickel concentrations in
      their serum specimens are close to the detection limits. For this reason, and
      because urine collection is painless, noninvasive, and convenient, urine is more
      practical than serum for the biological monitoring of nickel-exposed workers.
      Electrothermal atomic absorption spectrometry with Zeeman background correction
      is currently the method of choice for the analysis of nickel in biological
      materials. Procedures for quality assurance and strategies for biological
      monitoring are summarized, as performed in the author's laboratory, and current
      reference values are listed for nickel concentrations in urine and serum
      specimens from healthy unexposed persons.

PMID- 8159971
TI  - Normal concentrations of chromium in serum and urine--a TRACY project.
AB  - The validity of "normal" concentrations for total chromium in serum and urine (S
      Cr and U-Cr, respectively) in papers published mainly in the last decade were
      evaluated and graded by two investigators according to TRACY criteria. The
      results were in close agreement. Because of possible contamination during
      sampling from stainless steel needles, the description of the sample collection
      method was considered important. Documentation of analytical quality control was
      emphasized. The chromium concentrations were categorized according to
      nonoccupational conditions that could influence the levels. Eighty-seven
      publications reporting chromium concentrations in blood and 58 on U-Cr were
      evaluated, 53 dealing with S-Cr and 41 with U-Cr being found suitable for the
      TRACY project. In selected publications the arithmetic mean values presented for
      S-Cr and U-Cr in individuals with no known exposure were within the following
      ranges: 1-3 nmol.1-1 for S-Cr and 2-10 nmol.1-1 or 0.2-1 mumol.mol creatinine-1
      for U-Cr.

PMID- 8159972
TI  - Biological monitoring of exposure to mercury vapor.
AB  - Biological monitoring of mercury in whole blood (B-Hg) or urine (U-Hg) can be
      used to assess exposure to mercury vapor if the kinetics and other sources of
      variation are taken into account. Its rapid rise postexposure makes B-Hg a good
      indicator of recent exposure peaks, while U-Hg (corrected for urinary flow rate)
      reflects average long-term exposure. However, high intraindividual variation
      sometimes requires the average of several U-Hg determinations. In the general
      population, methylmercury from fish and mercury from dental amalgam influence B
      Hg and U-Hg, respectively, and must be considered if other exposures are being
      monitored. The quantitative relations between mercury in biological fluids and
      critical organs are poorly understood. Monitoring U-Hg is useful for assessing
      the risk of adverse effects and the need for preventive measures. At average U-Hg
      levels of about 50 micrograms.g creatinine-1 (28 nmol.mmol creatinine-1) the
      prevalence of symptoms and slight objective changes in the central nervous system
      and the excretion of certain urinary proteins are increased.

PMID- 8159973
TI  - Biological monitoring of arsenic, lead and cadmium in occupationally and
      environmentally exposed pregnant women.
AB  - Lead and cadmium in blood (B-Pb and B-Cd, respectively) and arsenic in urine (U
      As) were analyzed three times during pregnancy for women living around a metal
      smelter and women living in a reference town. The B-Pb levels were significantly
      higher in the smelter town. In the women of both towns, the B-Pb levels increased
      during pregnancy. Women who were employed at the smelter had higher B-Pb levels
      than women in the surrounding area. There were no significant differences in the
      B-Cd levels between the smelter and reference towns, except for non- and ex
      smokers at the onset of pregnancy. No difference between the two areas was seen
      among the smokers, whose cadmium levels were twice those of non- and ex-smokers.
      There were no significant differences in the U-As levels, which were comparable
      with previously reported values in Sweden.

PMID- 8159974
TI  - In vivo x-ray fluorescence measurements of cadmium and lead.
AB  - Information about the body burden of a metal is important in the evaluation of
      both exposure and risk. In vivo methods for determining cadmium and lead have
      become available in the last 20 years. Thus cadmium in kidney can be assessed by
      neutron activation or X-ray fluorescence analysis. The X-ray fluorescence
      technique allows kidney cadmium determinations even in subjects without
      occupational exposure. The level reflects the burden, long-term exposure, and the
      risk of toxic effects. Furthermore, in vivo determination of lead in finger bone,
      tibia, or calcaneus by X-ray fluorescence indicates long-term exposure and should
      become a valuable tool in epidemiologic studies, especially of chronic effects.

PMID- 8159975
TI  - Biological monitoring of inorganic lead.
AB  - In exposure and risk evaluation, monitoring lead biologically has several
      advantages over technical exposure assessment. Traditionally, the concentration
      in blood (B-Pb) has been widely used. However, the erythrocytes tend to become
      saturated, and this phenomenon causes a nonlinear relationship between B-Pb and
      uptake and between metabolic and toxic effects and B-Pb. Recently, several
      techniques for determining lead in finger bone, tibia, or calcaneus in vivo by X
      ray fluorescence have become available. Bone lead reflects long-term exposure and
      should prove valuable in epidemiologic studies. Mobilization tests have been
      widely used to monitor lead biologically. They mainly seem to reflect the lead in
      soft tissues and may not be an index of total body burden, most of which is in
      the skeleton. It thus seems that, at least in adults, mobilization tests do not
      provide more information than traditional lead determinations in blood and urine.
      A metabolic model for lead in humans is presented.

PMID- 8159976
TI  - Reference values for the biological monitoring of trace elements in environmental
      and occupational health. Report of a panel discussion in Stockholm 25 May 1992.

PMID- 8159977
TI  - Carcinogenicity of trace elements with reference to evaluations made by the
      International Agency for Research on Cancer.
AB  - The monograph program of the International Agency for Research of on Cancer has
      evaluated many trace elements for their carcinogenicity to humans. Five groups of
      compounds were considered human carcinogens: arsenic and arsenic compounds,
      beryllium and beryllium compounds, cadmium and cadmium compounds, hexavalent
      chromium compounds, and nickel compounds. Antimony trioxide, cobalt and cobalt
      compounds, lead and inorganic lead compounds, methylmercury compounds, and
      metallic nickel were considered possibly carcinogenic to humans. Antimony
      trisulfide, trivalent chromium compounds, metallic chromium, ferric oxide,
      organolead compounds, metallic mercury, inorganic mercury compounds, selenium and
      selenium compounds, and titanium dioxide were not classifiable. Trace elements
      studied to a limited extent include copper, manganese, tin, vanadium, and zinc.
      Among the problems are the lack of relevant data, the definition of active
      species, the extrapolation of the results of experimental studies to humans, the
      methodological problems of epidemiologic studies, and the possible
      anticarcinogenic activity of some trace elements.

PMID- 8159978
TI  - Biological monitoring of toxic metals.
AB  - The biological monitoring of metals, when used properly, allows total exposure to
      a particular metal to be measured from various media. It takes into consideration
      inter- and intraindividual variations in uptake due to differences in metabolism
      and physical work load and can be used to identify individuals, or groups of
      individuals, with high exposure or at high risk. As many metals are retained for
      long periods, biological monitoring may not only provide information on recent
      exposure, but also on exposure which occurred a long time ago. Under optimal
      conditions, the concentration of a metal in biological media can be used to
      assess exposure, the concentration of the metal in the target or critical organ
      (ie, the organ where the adverse effects are first observed) and the risks for
      adverse effects. This paper gives an overview of several important aspects of
      biological monitoring but does not provide detailed information on particular
      metals.

PMID- 8159980
TI  - Search for molecular mechanisms in the genotoxicity of nickel.
AB  - This paper reviews recent studies done in the author's laboratory on molecular
      mechanisms of nickel genotoxicity, using as an experimental model the teratogenic
      effects of bivalent nickel ions (Ni2+) in South Africa frogs (Xenopus laevis). A
      Ni(2+)-binding protein, pNiXa, was identified in Xenopus oocytes and embryos
      (molecular weight 45 kDa, isoelectric point approximately 8.5) with a strong
      homology to human alpha 1-antitrypsin, alpha 1-antichymotrypsin, and other serine
      proteinase inhibitors. CNBr peptides of pNiXa showed sequence identity to Ep45.
      Nondenatured pNiXa, purified by nickel affinity chromatography, inhibits bovine
      alpha 1-chymotrypsin. The possibility that pNiXa plays a key role in Ni2+
      teratogenesis is indicated by (i) the avidity of pNiXa for Ni2+, (ii) the
      presence of pNiXa when the embryos are susceptible to Ni2+ teragenesis, and (iii)
      the potential of the (HX)n-motif to form Ni2+ complexes that could catalyze the
      formation of oxygen free radicals and thereby damage deoxyribonucleic acid (DNA)
      and chromosomes.

PMID- 8159979
TI  - Molecular targets of nickel and chromium in human and experimental systems.
AB  - Water-insoluble nickel compounds tend to be carcinogenic because they enter cells
      through phagocytosis. Highly water-soluble nickel salts, such as nickel chloride,
      do not enter cells well and thus are not carcinogenic in vivo. Carcinogenic
      nickel compounds produce selective damage to heterochromatic regions in Chinese
      hamster chromosomes, probably because of the high concentration of proteins and
      amino acids in this highly condensed genetically inactive chromatin region.
      Bivalent nickel ions are highly affinitive to amino acids as compared with
      deoxyribonucleic acid (DNA). The interaction with proteins is believed to cause
      this effect. In addition, when nickel binds to proteins, it can be oxidized, and
      DNA protein damage ensues. A new method detects DNA-protein cross-links induced
      by various agents, such as nickel, chromium and cis-platinum. It has demonstrated
      an increase in DNA-protein cross-links in cultured cells from animals treated
      with chromate and welders exposed to welding fumes.

PMID- 8159981
TI  - Role of chemical species and exposure characteristics in cancer among persons
      occupationally exposed to chromium compounds.
AB  - Epidemiologic studies on chromate workers are considered with special reference
      to the valency of chromium compounds, carcinogenic potency, and water solubility.
      It is assumed that all hexavalent chromium compounds are carcinogenic to humans
      when inhaled but that there is no evidence that trivalent compounds are
      carcinogenic. It is suggested that zinc chromate is a highly potent carcinogen
      and also that calcium chromate may be carcinogenic. There are indications that
      chromates of low water solubility may be less potent carcinogens than compounds
      of greater solubility. Evidence is also presented for possible interactions with
      smoking and other factors involved in work-related cancers.

PMID- 8159982
TI  - Lung cancer in smelter workers--interactions of metals as indicated by tissue
      levels.
AB  - The concentrations of the elements antimony, arsenic, cadmium, chromium, cobalt,
      lanthanum, lead, selenium, and zinc were determined in lung tissue of 85
      decreased smelter workers by neutron activation analysis and atomic absorption
      spectrophotometry. The concentrations of all these elements, except zinc, were
      significantly higher among the workers as compared with rural referents. Workers
      who died from lung cancer (N = 7) had the lowest lung selenium content relative
      to other metals, both compared with workers with other diseases and with rural (N
      = 15) and urban (N = 10) referents. The low lung tissue levels may have
      influenced the development of lung cancer. The highest lung cadmium
      concentrations were observed in the lung cancer group, in which, however, smokers
      and ex-smokers were over-represented. The observations make it likely that the
      excess lung cancer risk in this smelter environment is multifactorial in
      character, involving interactions between both carcinogenic and anticarcinogenic
      factors.

PMID- 8159983
TI  - Epidemiologic studies of occupational cancer as related to complex mixtures of
      trace elements in the art glass industry.
AB  - In the art glass industry workers run increased risks of dying from several types
      of cancer, cardiovascular diseases, and cerebrovascular diseases. This paper
      considers the diseases of glass workers in relation to exposure to particular
      elements, a high degree of correlation being found for some of them. Case
      referent evaluations showed an association between stomach cancer and exposure to
      a mixture of elements, namely, arsenic, copper, nickel, and manganese, and to
      some extent also to lead and chromium. For colon cancer, a clearly increasing
      trend in risk was seen with increasing use of antimony, and to some extent also
      with increasing use of lead, the two elements being strongly correlated. For lung
      cancer no obvious correlation with any metal could be found. In addition, the
      risk for death from cardiovascular disease was fairly evenly distributed,
      although slightly more related to increasing consumption of the strongly
      correlated metals nickel and copper.

PMID- 8159984
TI  - [Evaluation of deviating liver tests in ambulatory practice].
AB  - The finding of disturbed hepatic function, associated with an unclear clinical
      picture or during of a health checkup, is frequent. A physician's approach to a
      patient presenting disturbed hepatic function tests does not depend on well
      defined algorithms but requires a sound knowledge of hepatic function tests and
      indicators of hepatobiliary disease. There are two major categories of hepatic
      function tests: non-specific tests which may indicate the existence of hepatic
      disease, and specific tests which permit assessment of the nature of hepatic
      damage. To facilitate the search for an etiology, it is helpful to classify
      hepatobiliary diseases according to the type of disturbance of hepatic function.
      One may speak of hepatocellular necrosis if elevation of the transaminases is the
      sole or predominant feature, and of cholestasis if the elevation solely or
      essentially involves the alkaline phosphatases and gamma-GT. Chronic hepatitis C,
      alcoholism and obesity frequently underline an isolated elevation of the
      transaminases.

PMID- 8159985
TI  - [Treatment of autoimmune chronic active hepatitis and of primary biliary
      cirrhosis].
AB  - Several subtypes of autoimmune chronic active hepatitis can be distinguished
      today, one variant of which seems to be associated with active hepatitis C virus
      infection. Except for the latter, all types respond well to immunosuppressive
      therapy with prednisone (+/- azathioprine). Therapy has been shown to prolong
      survival, but the disease nevertheless often progresses to cirrhosis. For
      conservative therapy of primary biliary cirrhosis, D-penicillamine is
      contraindicated and several immunosuppressants investigated are associated with
      unacceptable side effects; ursodeoxycholic acid, colchicine and perhaps
      methotrexate seem to be promising, but none has been proven to prolong survival.
      Therefore, patients with primary biliary cirrhosis should still be included in
      therapeutic trials. In the advanced stages of both diseases liver transplantation
      remains an effective therapy.

PMID- 8159986
TI  - [Laparoscopic cholecystectomy: current status].
AB  - Since its introduction a few years ago, laparoscopic cholecystectomy has become
      today the standard treatment of gallbladder stones. Compared to open surgery it
      involves little change in the preoperative investigations. There has been,
      especially in the beginning of the learning curve, a demand for preoperative
      visualization of the bile duct anatomy and for exclusion of intraductal stones.
      Thus the incidence of preoperative ERCP has risen with the development of
      laparoscopic cholecystectomy. For the advanced laparoscopic surgeon, the
      indications for laparoscopic cholecystectomy are the same as for open surgery.
      The benefits of laparoscopy for the patient are obvious and the results are
      favourable. Bile duct injury is a very severe complication and, at the beginning
      of the learning curve, the incidence has been somewhat higher than in open
      surgery. Therefore, proper training in laparoscopic surgery and quality control
      are necessary. Many reports on advanced laparoscopic procedures have already been
      published, but only the future will show the limits of this technique.

PMID- 8159987
TI  - [The value of shockwave lithotripsy].
AB  - The standard treatment for symptomatic cholecystolithiasis remains surgery, the
      present method of choice being laparoscopic cholecystectomy. Noninvasive
      treatment options are available, but should be restricted to selected cases.
      Extracorporal shock wave lithotripsy (ESWL) is an alternative to noninvasive
      treatment, provided the patients are carefully selected. The main disadvantages
      include prolonged administration of gall salts and the problem of stone
      recurrence.

PMID- 8159988
TI  - [Relation among the nervous, immune and endocrine systems].

PMID- 8159989
TI  - [Neuronotrophic factors and proto-oncogene].

PMID- 8159990
TI  - [Molecular mechanism of the effect of human chorionic gonadotropin--receptor
      binding and function of glycochain].

PMID- 8159991
TI  - [Drug metabolism].

PMID- 8159992
TI  - [Changes in sodium, calcium and potassium during ischemia and reperfusion of
      myocardium].

PMID- 8159993
TI  - [Na+/H+ exchange and its significance in myocardial reperfusion injury].

PMID- 8159994
TI  - [Neurobiologic characteristics of spinal sympathetic preganglionic neurons].

PMID- 8159995
TI  - [Central pain modulation: descending facilitatory system].

PMID- 8159996
TI  - [Regulation of pro-opiomelanocortin gene expression in the pituitary gland and
      hypothalamus].

PMID- 8159997
TI  - [Recombinant immunotoxin].

PMID- 8159998
TI  - [The possible mechanism of permissive action by glucocorticoids].

PMID- 8159999
TI  - [Glycine receptors].

PMID- 8160000
TI  - [Cardionatrin and pulmonary hypertension].

PMID- 8160001
TI  - [Tracheobronchial circulation and asthma].

PMID- 8160002
TI  - [Long-term potentiation and its relation to learning and memory].

PMID- 8160003
TI  - [Relation between bone gla protein and bone metabolism in weightlessness].

PMID- 8160004
TI  - Viral recombination in transgenic plants.

PMID- 8160005
TI  - Inhibition of Rev-mediated HIV-1 expression.

PMID- 8160006
TI  - Scientific misconduct. NIH tightens clinical trials monitoring.

PMID- 8160007
TI  - Pesticides and breast cancer: no link?

PMID- 8160008
TI  - Cancer prevention. Beta-carotene: helpful or harmful?

PMID- 8160009
TI  - Vaccines get a new twist.

PMID- 8160010
TI  - Gene transfer to spark a failing heart.

PMID- 8160011
TI  - Diet and health: what should we eat?
AB  - Many recent studies have implicated dietary factors in the cause and prevention
      of important diseases, including cancer, coronary heart disease, birth defects,
      and cataracts. There is strong evidence that vegetables and fruits protect
      against these diseases; however, the active constituents are incompletely
      identified. Whether fat per se is a major cause of disease is a question still
      under debate, although saturated and partially hydrogenated fats probably
      increase the risk of coronary heart disease. One clear conclusion from existing
      epidemiologic evidence is that many individuals in the United States have
      suboptimal diets and that the potential for disease prevention by improved
      nutrition is substantial.

PMID- 8160012
TI  - The role of interleukin-6 in mucosal IgA antibody responses in vivo.
AB  - In mice with targeted disruption of the gene that encodes interleukin-6 (IL-6),
      greatly reduced numbers of immunoglobulin A (IgA)-producing cells were observed
      at mucosae and grossly deficient local antibody responses were recorded after
      mucosal challenge with either ovalbumin or vaccinia virus. The IgA response in
      the lungs was completely restored after intranasal infection with recombinant
      vaccinia viruses engineered to express IL-6. These findings demonstrate a
      critical role for IL-6 in vivo in the development of local IgA antibody responses
      and illustrate the effectiveness of vector-directed cytokine gene therapy.

PMID- 8160013
TI  - Loudness-coding mechanisms inferred from electric stimulation of the human
      auditory system.
AB  - Two distinct physiological mechanisms underlying loudness sensation were inferred
      from electric stimulation of the human auditory nerve and brainstem. In contrast
      to a power function relating loudness and stimulus intensity in acoustic hearing,
      loudness in electric stimulation of the auditory nerve depends on stimulus
      frequency. Loudness is an exponential function of electric amplitude for high
      frequencies and is a power function for low frequencies. A frequency-dependent,
      two-stage model is suggested to explain the loudness function, in which the first
      stage of processing is performed by a mechanical mechanism in the cochlea for
      high-frequency stimuli and by a neural mechanism in the cochlear nucleus for low
      frequency stimuli.

PMID- 8160014
TI  - Bacillus subtilis SpoIIIE protein required for DNA segregation during asymmetric
      cell division.
AB  - Sporulation in Bacillus subtilis begins with an asymmetric cell division,
      producing a smaller prespore and a larger mother cell, both of which contain
      intact copies of the chromosome. The spoIIIE gene is required for chromosome
      segregation into the prespore compartment. The effects of the spoIIIE36 mutation
      on sigma F-dependent transcription are an indirect consequence of the failure of
      certain genes to enter the cellular compartment in which their transcription
      factor has become active. SpoIIIE may also be required to prevent sigma F from
      becoming active in the mother cell.

PMID- 8160015
TI  - A neurochemically distinct third channel in the macaque dorsal lateral geniculate
      nucleus.
AB  - The primate visual system is often divided into two channels, designated M and P,
      whose signals are relayed to the cerebral cortex by neurons in the magnocellular
      and parvicellular layers of the dorsal lateral geniculate nucleus. We have
      identified a third population of geniculocortical neurons in the dorsal lateral
      geniculate nucleus of macaques, which is immunoreactive for the alpha subunit of
      type II calmodulin-dependent protein kinase. This large third population occupies
      interlaminar regions (intercalated layers) ventral to each principal layer.
      Retrograde labeling of kinase-immunoreactive cells from the primary visual cortex
      shows that they provide the geniculocortical input to cytochrome oxidase-rich
      puffs in layers II and III.

PMID- 8160016
TI  - Gating current noise produced by elementary transitions in Shaker potassium
      channels.
AB  - Gating currents provide a direct record of the spatial rearrangement of charges
      occurring within the protein of voltage-sensitive ion channels. If the elementary
      charges move as very brief discrete pulses of current, they will produce
      fluctuations in the macroscopic gating current. The variance of such fluctuations
      in gating currents was measured in Shaker potassium channels expressed in Xenopus
      oocytes with a sufficiently high recording bandwidth to estimate the magnitude
      and time distribution of the elementary transition charge movements. Channel
      activation occurred in two sequential stages. The first stage consisted of
      numerous, fast transitions, each moving small amounts of charge that contributed
      little to the fluctuation in gating current, whereas the second stage, which
      contributed the bulk of the fluctuation, was represented by a number of discrete,
      correlated transitions, one or more of which carried a charge of at least 2.4
      elementary charges across the membrane field.

PMID- 8160017
TI  - Enhanced myocardial function in transgenic mice overexpressing the beta 2
      adrenergic receptor.
AB  - Transgenic mice were created with cardiac-specific overexpression of the beta 2
      adrenergic receptor. This resulted in increased basal myocardial adenylyl cyclase
      activity, enhanced atrial contractility, and increased left ventricular function
      in vivo; these parameters at baseline in the transgenic animals were equal to
      those observed in control animals maximally stimulated with isoproterenol. These
      results illustrate a useful approach for studying the effect of gene expression
      on cardiac contractility. Because chronic heart failure in humans is accompanied
      by a reduction in the number of myocardial beta-adrenergic receptors and in
      inotropic responsiveness, these results suggest a potential gene therapy approach
      to this disease state.

PMID- 8160018
TI  - Muscle biochemistry and a genetic study of myotonic dystrophy.

PMID- 8160019
TI  - A truncated erythropoietin receptor and cell death: a reanalysis.

PMID- 8160020
TI  - Antibiotic selection for infections in obstetric patients.

PMID- 8160021
TI  - Human immunodeficiency virus infection in pregnancy.

PMID- 8160022
TI  - Viral hepatitis in pregnancy.
AB  - Hepatitis A is usually a benign, self-limited infection. A chronic carrier state
      does not exist, and perinatal transmission does not occur. Hepatitis B may cause
      chronic infection, and infants delivered to infected mothers are at considerable
      risk of developing neonatal hepatitis. Passive and active immunization with HBIG
      and HBV is highly effective in preventing perinatal transmission. Hepatitis D
      typically occurs as a coinfection or superinfection with hepatitis B. Patients
      infected with both viruses are at high risk for chronic liver disease. Perinatal
      transmission of hepatitis D can be prevented by the immunoprophylaxis used for
      hepatitis B. Non-A, non-B hepatitis occurs in two distinct forms: parenterally
      transmitted hepatitis C and enterically transmitted hepatitis E. Perinatal
      transmission of hepatitis C can occur, particularly in women who are concurrently
      infected with the human immunodeficiency virus. Neonatal immunoprophylaxis is not
      yet available. Hepatitis E may be associated with high maternal mortality rates
      in developing nations. However, a chronic carrier state does not exist, and
      perinatal transmission does not occur. Table 2 summarizes the most important
      features of each form of viral hepatitis.

PMID- 8160023
TI  - Cytomegalovirus infection in pregnancy.
AB  - CMV is the most common cause of intrauterine infection in this country, affecting
      approximately 1% of newborns. As such, CMV infection is a leading cause of
      deafness and an important contributor to learning disabilities. The virus is
      transmitted through close contact with infected secretions as well as
      transplacentally, through sexual contact, and through blood transfusion and organ
      transplantation. CMV has a high prevalence in the population; antibody to the
      virus can be detected in 50% to 85% of individuals. Like herpes simplex, the
      virus can be reactivated and cause recurrent infection. Congenital disease occurs
      in about 30% to 40% of women with primary infection. Ten percent of infants with
      congenital infection will have clinical disease at birth. Of these, as many as
      30% die. Ninety percent of survivors have sequelae such has deafness, mental
      retardation, chorioretinitis, and motor deficits. The other 90% of infants with
      congenital infection are asymptomatic at birth, but 5% to 17% develop long-term
      sequelae. Congenital disease also occurs with recurrent maternal infection in
      about 0.2% to 1% of immune women. Congenital infection due to recurrent disease
      is far less severe, and less than 10% of affected infants have long-term sequelae
      (Fig 3). The diagnosis of congenital infection can be established using a
      combination of ultrasound, amniocentesis, and cordocentesis. Viral culture of
      neonatal urine can confirm the diagnosis after birth. Routine screening of the
      pregnant population is not currently recommended because present laboratory
      methods limit the ability to differentiate primary from recurrent infection.
      Preventive efforts at this time must focus on good hygiene, limited intimate
      contact with infected children, and responsible sexual practices.

PMID- 8160024
TI  - Varicella in pregnancy.

PMID- 8160025
TI  - Parvovirus infection in pregnancy.
AB  - Many nonimmune pregnant women will be exposed to parvovirus B19 infection.
      Postexposure passive immunization is not currently recommended. Once there is
      maternal infection, maternal disease is usually self-limited, but the effects to
      the fetus can be devastating. Even so, additional studies of the risks and
      benefits of intrauterine therapy such as transfusion and digitalization are
      necessary before definitive recommendations can be made. Cases where congenital
      viral infection is suspected should be handled in an appropriate manner and
      should include serology on mother and infant (both acute and convalescent), viral
      cultures, and ophthalmologic evaluation. Health care workers must be aware that
      the infant and its body fluids and organs may be infective to susceptible nursery
      and laboratory personnel.

PMID- 8160026
TI  - Intra-amniotic infections.

PMID- 8160027
TI  - Puerperal infections.

PMID- 8160028
TI  - Group B streptococcal infection in pregnancy.

PMID- 8160029
TI  - Sexually transmitted diseases in pregnancy.

PMID- 8160030
TI  - Fibro-osseous lesions of the face and skull with aneurysmal bone cyst formation.
AB  - Aneurysmal bone cyst engraftment on benign fibro-osseous lesions, well known to
      occur in the extracranial skeleton, has been reported infrequently in the
      craniofacial bones. When this combined lesion occurs in the skull the clinical
      and radiographic features often suggest an aggressive neoplasm. The clinical,
      radiographic, and pathologic features of five cases are presented, and this
      uncommon lesion of the craniofacial bones is discussed in view of these cases and
      those reported in the literature.

PMID- 8160031
TI  - Magnetic resonance imaging of occult fractures of the proximal femur.
AB  - The evaluation of the painful hip in the elderly osteoporotic patient with normal
      plain radiographs can be difficult. We studied 15 osteopenic patients with normal
      plain radiographs and suspected hip fractures with magnetic resonance (MR)
      imaging and found MR to be an excellent aid in detecting occult fractures. A
      clear fracture was seen in 10 of the 15 patients, who then underwent surgical
      repair based on the MR study. The remaining patients had no MR-demonstrable
      fracture and were successfully treated nonoperatively. Some believe that a
      negative bone scan in this population of patients should be repeated within 3
      days prior to a definitive "no fracture" decision being made. Unfortunately, bone
      scanning lacks spatial resolution, and increased osteoblastic activity may be
      caused by other pathologic processes besides fracture. Two of the 15 patients had
      MR-demonstrated bone infarcts near the fracture. One patient also had femoral
      head osteonecrosis on the side of the fracture. One patient with metastatic
      prostatic carcinoma had a hip fracture and one patient with metastatic breast
      carcinoma had no fracture. No only is MR imaging an excellent technique for
      delineating occult fractures, but due to its spatial resolution, associated bone
      disorders adjacent to fractures can be detected in most instances. From a cost
      perspective, rapid diagnosis and early treatment of an occult femoral fracture is
      advisable. A reduced hospital stay pending diagnosis and the early institution of
      definitive therapy also decrease the chance that a simple non-displaced fracture
      will displace and require more complex management with resultant increased
      morbidity and cost.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8160032
TI  - Giant solitary synovial chondromatosis.
AB  - The purpose of this report is to describe giant solitary synovial chondromatosis,
      a previously unrecognized feature of synovial chondromatosis that may
      histologically and radiographically mimic a malignant neoplasm. Giant solitary
      synovial chondroma is an intra- and/or extraarticular lesion measuring over 1 cm
      in size and sometimes as large as 20 cm. The radiographic appearance is that of a
      large, well-marginated mass either of irregular feathery calcification from
      coalescence of multiple small synovial chondromas, or a rounded calcified mass
      from the growth of a single synovial chondroma. Radiographically, giant solitary
      synovial chondromatosis may appear similar to chondrosarcoma and parosteal
      osteosarcoma.

PMID- 8160033
TI  - Ossification and pseudoepiphysis formation in the "nonepiphyseal" end of bones of
      the hands and feet.
AB  - Metacarpals, metatarsals, and phalanges were studied to assess the developmental
      morphology of "secondary" ossification in the "nonepiphyseal" ends of these bones
      as well as the formation of the pseudoepiphysis as an epiphyseal ossification
      variant. Both direct ossification extension from the metaphysis into the
      epiphysis and pseudoepiphysis formation preceded, and continued to be more mature
      than, formation and expansion of the "classic" epiphyseal (secondary)
      ossification center at the opposite end of each specific bone. Direct metaphyseal
      to epiphyseal ossification usually started centrally and expanded
      hemispherically, replacing both physeal and epiphyseal cartilage simultaneously.
      In contrast, when remnants of "physis" were retained, while juxtaposed epiphyseal
      cartilage was replaced, a pseudoepiphysis formed. There were three basic patterns
      of pseudoepiphysis formation. First, a central osseous bridge extended from the
      metaphysis across the "physis" into the epiphysis and subsequently expanded to
      create a mushroom-like osseous structure. In the second pattern a peripheral
      osseous bridge formed, creating either an osseous ring or an eccentric bridge
      between the metaphysis and the epiphysis. In the third pattern, multiple bridging
      occurred. In each situation the associated remnant "physis" lacked typical cell
      columns and was incapable of significantly contributing to the postnatal
      longitudinal growth of the involved bone. Pseudoepiphyses were well formed by 4-5
      years and coalesced with the rest of the bone months of years before skeletal
      maturation was attained at the opposite epiphyseal end, which ossified in the
      typical pattern (i.e., formation of a secondary center de novo completely within
      the cartilaginous epiphysis). This process may also affect the development and
      appearance of ossification within the longitudinal epiphyseal bracket ("delta
      phalanx").

PMID- 8160034
TI  - Hyperostosis and osteoarthritis in patients surviving after tetanus.
AB  - Twenty patients (12 men and 8 women) who had survived tetanus were examined for
      bone and joint abnormalities, 1-9 years after the disease. The radiographic
      findings in the elbows were abnormal in 13 out of 20 patients, as were the
      shoulders of all 3 patients examined. Insertion hyperostoses were found at the
      elbow and/or in the shoulder region in 5 (25%) of the patients. The hyperostoses
      were bilateral in 3 patients. One of the patients with hyperostoses also had
      calcifications in the soft tissue of the elbow. The abnormalities were associated
      with mild clinical symptoms. Trauma to the periosteum caused by repeated traction
      of muscular contractions is possibly the causative mechanism. Twelve patients
      (60%) had osteoarthritis of the elbow joint presumably secondary to the violent
      stress to the joint.

PMID- 8160035
TI  - The value of contrast arthrography in assessing loosening of symptomatic
      uncemented total hip components.
AB  - Twenty-five patients with symptomatic uncemented total hip components were
      studied with contrast arthrography prior to surgical exploration. All but one had
      uncemented femoral stems and 16 had an uncemented acetabular component. As judged
      by the findings at surgery, on the femoral side the sensitivity, specificity, and
      accuracy of arthrography were 57%, 60%, and 58% respectively. There was a
      relatively high incidence of both false positives (17%) and false negatives
      (25%). On the acetabular side sensitivity, specificity, and accuracy were 29%,
      89%, and 62.5%. False negatives were common (31%), while there was only one false
      positive. The results in this small series show that arthrography has distinct
      limitations in identifying the fixation status of uncemented total hip
      components.

PMID- 8160036
TI  - Clinical use of the simple 3D-calculation in scoliosis.
AB  - In this paper we show the clinical application of a simple method for calculating
      three-dimensional shape in scoliosis by the use of two tables based on normal
      standard X-rays in the anteroposterior and lateral projections. The three
      dimensional alignment should be considered in both conservative and operative
      correction. In 57 patients with 87 scoliotic curves we measured the well-known
      Cobb angle (alpha) and determined the vertebral rotation according to the method
      of Nash and Moe. We compared this information with the results of the calculated
      three-dimensional angles of scoliosis (angle beta between the curvature plane and
      the sagittal plane, angle sigma as the true angle of scoliosis in this curvature
      plane). In 76 curves (87%) our method was practicable. The true angle sigma is
      always higher than the projected angle alpha, especially in the clinically
      relevant range of 20 degrees-40 degrees. Poor correlation is shown between the
      projected angle alpha and the true angle sigma (r = 0.41 for thoracic curves and
      r = 0.57 for lumbar curves) and almost no correlation between vertebral rotation
      and the true angle sigma (r = 0.10 for thoracic curves and r = 0.44 for lumbar
      curves) and the curvature plane (beta) (r = 0). The three-dimensional shape of
      scoliosis cannot be estimated by the well-established projected angles and
      indices and we recommend the use of our simple method for the radiological
      investigation of scoliotic patients.

PMID- 8160037
TI  - Cortical bone mass in Nigerian children: an anthropometric assessment.
AB  - Cortical bone mass was quantified in 1278 Nigerian children (695 males and 583
      females) aged 3-16 years in a prospectively designed cross-sectional and
      longitudinal study. The total bone width (T) and medullary cavity width (M) were
      measured at the midshaft of the second metacarpal bone using a direct reading
      caliper. From the above measurements the cortical width (C), cortical area (CA),
      and percent cortical area (PCA) were calculated using the method of Garn et al.
      and showed a progressive increase of T, C, CA and PCA, reaching a plateau at 15
      years. At all ages, the values for both T and M are higher in males than in
      females. On the other hand, and contrary to established normal values amongst
      both white and black Americans, between the ages of 9 and 15 the female values
      for C are higher than those for males. This difference is greatest at the age of
      12 years (p < 0.001). The implication of this finding may be that during these
      years, African male children do not compensate for the increased endosteal
      resorption with a greater total cortical width (T), since the medullary width in
      females remains relatively constant over the years.

PMID- 8160038
TI  - Bone marrow edema in osteoid osteoma.

PMID- 8160039
TI  - Case report 806: Monostotic Paget's disease of the hand (fifth metacarpal).
AB  - Monostotic Paget's disease of bone is an uncommon disease, reported in the hand
      in only a few instances. We have described an additional case involving a
      metacarpal bone in a 43-year-old man. We believe this disease should be
      considered in the radiological differential diagnosis of lytic expansile,
      subchondral lesions of the hand.

PMID- 8160040
TI  - Case report 819: Periosteal Ewing's sarcoma of the tibia.
AB  - An exceptionally rare case of periosteal Ewing's sarcoma involving the mid shaft
      of the right tibia was reported. In this case, MRI was the technique that
      confirmed the integrity of the bone marrow. The clinical, radiographic, and
      histopathologic features of Ewing's sarcoma have been discussed, as has the
      differential diagnosis of the periosteal type of this tumor.

PMID- 8160041
TI  - Case report 820: Granular cell tumor of striated muscle.

PMID- 8160042
TI  - Case report 821: Parosteal ossifying lipoma of femur.
AB  - Parosteal lipoma with bony excrescences at the periosteal base of the tumor is
      rare. Only one case has been reported with osseous and cartilaginous nodules
      throughout the lipoma. We describe an additional case in a 39-year-old man. We
      emphasize the characteristic radiological appearance of the lesion as well as the
      possibility of a dual histogenesis for the osteochondromatous component. We also
      stress the great value of CT in establishing the diagnosis.

PMID- 8160043
TI  - Case report 822: Osteochondroma causing peroneal palsy-imaging evaluation.

PMID- 8160044
TI  - Case report 823: Fibro-osseous pseudotumor of the scapula.
AB  - A unique lesion discovered in the scapula of a 36-year-old woman is presented.
      The lesion has microscopic features resembling those of fibrous dysplasia and
      osteoid osteoma which we believe is identical to an entity previously only
      documented in the rib (fibro-osseous lesion of rib). We are of the opinion that
      the lesion probably represents a reactive response to trauma rather than a
      neoplasm and suggest the name of "fibro-osseous reparative pseudotumor" for this
      entity.

PMID- 8160045
TI  - Case report 824: Tuberculosis presenting as a soft tissue forearm mass in a
      patient with a negative tuberculin skin test.
AB  - Tuberculosis presenting as a soft tissue mass is rare. The diagnosis should be
      considered in patients with radiographic findings of massive soft tissue swelling
      and cortical bone destruction. Such patients may present with few clinical
      findings and have no evidence of prior exposure to tuberculosis or history of
      immunosuppression. Computed tomography may be of use in distinguishing infection
      from malignancy.

PMID- 8160046
TI  - Investment, health and development.

PMID- 8160047
TI  - Status of tuberculosis control in Thailand.
AB  - The national tuberculosis control program (NTP) was implemented in Thailand as
      integrated with the provincial general health services since 1967, with BCG
      vaccination successfully introduced from the beginning, but progress in expansion
      of case-finding and chemotherapy had only been achieved following the
      establishment of hospitals at the district level since the late seventies. At
      present, case-detection and treatment have operated in more than 95% of the 600
      district hospitals and 87 hospitals at provincial and regional levels, with
      patient follow-up by health centers, logistically supported and technically
      supervised by 12 zonal TB centers. The trend of the disease has shown noticeable
      decline as indicated by the three national surveys in 1962, 1977 and 1991, that
      is, morbidity rate as suspected by x-ray of 2.1%, 1.4% and 1.01%; infectious case
      rate of 0.5%, 0.31% and 0.24% respectively, a reduction of about 2-3% per year.
      The infection rate of children 0-14 years of age was found to be 15.2% in 1977;
      8.9% in 1983; and 5.18% in 1987, giving the annual risk of infection (ARI) of
      4.9%, 2.3% and 2.0% respectively. Currently the program detects and treats about
      31,000 smear-positive TB cases plus an equal number of smear-negative cases per
      year. Short-course chemotherapy was introduced since 1985 and expanded to cover
      all the former by 1991, resulting in improvement of the treatment success rate
      from less than 50% when using the old standard 18-24 months regimen to 70-80%. As
      the coverage of case detection and treatment is still only about 60% of the
      incidence or 30% of the prevalence, trials of primary health care approach have
      yielded substantially increased case detection coverage as well as improved cure
      rates. BCG vaccination as part of the Expanded Program on Immunization has
      reached 90-100% coverage of infants.

PMID- 8160048
TI  - Enterotoxigenic Escherichia coli and other causes of infectious pediatric
      diarrheas in Jakarta, Indonesia.
AB  - A hospital stool survey of Indonesian children less than 5 years of age
      determined the prevalence of diarrhea caused by enterotoxigenic Escherichia coli
      (ETEC) and other bacterial enteropathogens, compared to non-diarrheic control
      patients. ETEC were the second most frequent cause of diarrhea, isolated from 16
      of 194 (8.2%) of patient's stools compared to 2 of 97 (2.1%) of control stools.
      The highest prevalence was in infants 12 to 23 months of age (17.9%).

PMID- 8160049
TI  - The 1990-1991 outbreak of melioidosis in the Northern Territory of Australia:
      clinical aspects.
AB  - From November 1990 to June 1991, 33 cases of acute melioidosis were diagnosed in
      tropical Northern Territory, Australia during an exceptionally wet monsoon.
      Eighteen (55%) were alcoholic, 16 (48%) diabetic and only 4 (12%, all survivors)
      had no risk factors. Twenty-seven (82%) were considered recent infection, with an
      incubation period of 3-21 days (mean 14) documented in eight cases with presumed
      cutaneous inoculation. Fourteen patients presented with pneumonia (4 septicemic)
      and of 11 others with septicemia 4 had genitourinary foci. Three of 4 with
      splenic abscesses required splenectomy. Three had only skin/soft tissue
      infection. One patient with brainstem encephalitis needed prolonged ventilation.
      Overall mortality was 36% (12 cases, including three relapses), despite therapy
      with ceftazidime and intensive care facilities. Pseudomonas pseudomallei is the
      commonest diagnosed cause of fatal bacteremic pneumonia at Royal Darwin Hospital
      and emphasis is placed on early appropriate antibiotic therapy and compliance
      with maintenance therapy for at least three months.

PMID- 8160050
TI  - Epidemiological study of Pseudomonas aeruginosa isolated from clinical specimens.
AB  - The epidemiology of Pseudomonas aeruginosa infection was studied in Siriraj
      Hospital. During April 1989-June 1990, P. aeruginosa 436 strains were isolated
      from clinical specimens of 260 patients, ie blood (19 strains), pus (192
      strains), sputum (159 strains) and urine (66 strains). By using a combination of
      serogroups and pyocin types as epidemiological markers, it was found that there
      were 10 serogroups and 8 pyocin types which can be differentiated into 33
      serogroup/pyocin types or patterns. The most common pattern was E 211111 (26.3%)
      followed by B 121614 (24.5%), G 373112 (13%) and L 888888 (7.1%), respectively.

PMID- 8160051
TI  - Bacteriophage typing of Vibrio fluvialis.
AB  - Six stable bacteriophages of Vibrio fluvialis were isolated from 44 surface water
      specimens collected in Thailand and Japan. Twelve different phages types were
      found among 109 V. fluvialis isolated from feces of diarrheal patients and the
      environment. Seventy-three percent (80/109) of these 109 isolates were typable
      with these phages. One phage type, designated as A (1) was predominant and
      accounted for 43% of the V. fluvialis examined. The six bacteriophages used in
      this typing scheme were stable for at least during a three-month storage at 4
      degrees C. This proposed bacteriophage typing scheme may be of valuable aid in
      tracing sources and routes of infection in outbreaks of V. fluvialis infection in
      man.

PMID- 8160052
TI  - Detection of Epstein-Barr virus DNA and HHV-6 DNA in tissue biopsies from
      patients with nasopharyngeal carcinoma by polymerase chain reaction.
AB  - A total of 34 tissue biopsies were collected from nasopharyngeal carcinoma (NPC)
      patients and 5 controls with non-NPC. Extracted DNA from tissue biopsies were
      analyzed for presence of specific gene sequences to EBV type A and type B, and
      HHV-6 by polymerase chain reaction (PCR). The different sequences of EBV type A
      and B were parts from the highly divergent forms of the EBV nuclear antigen 2
      (EBNA 2). The PCR amplified products for EBNA 2A and EBNA 2B were 115 and 119
      base pairs respectively whereas that of HHV-6 DNA was 776 base pairs. The results
      demonstrated that EBV DNA was detected in 32 of 34 cases (94.1%): 28 (82.3%) with
      type A, 2 (5.9%) with type B, and 2 (5.9%) with both types. EBV DNA of type A
      could be detected 1 (20%) of 5 controls. HHV-6 DNA was in 5 of 34 samples (14.7%)
      whereas HHV-6 DNA was not detectable in biopsy tissues from controls. The results
      show that in the NPC patient group, A type of EBV is predominant. Detection of
      HHV-6 DNA in patients group only might be resulted from reactivation of a latent
      infection or association with EBV-induction of NPC.

PMID- 8160053
TI  - The abbreviated 2-1-1 schedule of purified chick embryo cell rabies vaccination
      for rabies postexposure treatment.
AB  - During August 1988 to January 1990, the immunogenicity and safety of purified
      chick embryo cell rabies vaccine (PCEC) given by the conventional and abbreviated
      regimens in 82 vaccinees moderately to severely exposed to laboratory proven
      rabid animals were studied. The 16 vaccinees received PCEC six doses as
      conventional schedule on days 0, 3, 7, 14, 28 and 90, the 11 vaccinees received
      six doses of PCEC plus human rabies immune globulin (HRIG) on day 0. The 29
      vaccinees received an abbreviated schedule of PCEC as two doses on day 0, one
      dose each on days 7 and 21 and the 26 cases received PCEC abbreviated schedule
      plus HRIG on day 0. The kinetics of the neutralizing antibodies on days 0, 7, 14,
      28, 56, 180 and 365 were studied for comparative purpose. All vaccinees had high
      antibody levels from day 14 which last longer than a year and were safe after one
      year follow up. The adverse reactions of the vaccine were mild and self-limited.

PMID- 8160054
TI  - Fulminant hepatitis in dengue infection.
AB  - Eight cases of liver failure and encephalopathy were observed among twenty cases
      of grade 3 and grade 4 dengue hemorrhagic fever/dengue shock syndrome admitted to
      the Department of Pediatrics, University Hospital, Kuala Lumpur from January 1990
      to December 1991. All patients with deterioriation in mental status showed a
      marked increase in liver enzymes (aspartate and alanine aminotransaminases) and
      severe coagulopathy. Six patients needed cerebral protection, including
      ventilation, intravenous sedation and muscle relaxants. There was one death
      during the period of study and one case of residual hemiparesis in a boy who had,
      in addition, intracerebral hemorrhage. All other survivors had complete recovery
      of liver and neurological function.

PMID- 8160055
TI  - Screening of pig sera for antibodies to Japanese encephalitis virus using a dot
      enzyme immunoassay and IgM capture ELISA: comparison with the hemagglutination
      inhibition and plaque reduction neutralization tests.
AB  - A dot enzyme immunoassay for determination of antibodies to Japanese encephalitis
      virus was designed for use as a field technique for the surveillance of Japanese
      encephalitis virus activity among domestic pigs. The test was compared with the
      neutralization test and the hemagglutination inhibition test and found to be more
      sensitive than the hemagglutination inhibition test and comparable to the
      neutralization test in sensitivity but more simple to perform than either the
      neutralization or the hemagglutination inhibition tests. An IgM capture ELISA for
      the determination of JEV specific porcine IgM was also utilized to determine
      current infection rates in pigs. The tests which do not involve the determination
      of specific IgM are better used for testing sentinel animals for providing clues
      as to the rate of transmission of JEV among pigs. IgM tests determining acute
      infection are less likely to be useful unless animals are tested very frequently
      or if a great number of animals are tested at any one time.

PMID- 8160056
TI  - Comparative study between molecular hybridization and electron microscopy for the
      detection of hepatitis E virus.
AB  - The study describes a comparison between molecular hybridization using a non
      radiolabeled, thymine-thymine (TT) dimerized synthetic oligonucleotide
      complementary DNA probe and electron microscopy for the detection of hepatitis E
      virus genome in bile. Spot hybridization with the TT dimerized probe was found to
      be more sensitive and specific compared to electron microscopy.

PMID- 8160057
TI  - Axenic cultivation of Entamoeba histolytica from liver abscess and its zymodeme.
AB  - A local strain of Entamoeba histolytica, the HTH-56: MUTM from a human liver
      abscess was successfully axenized. The culture was initially established
      monoxenically in Diamond's TYI-S-33 medium in the presence of Crithidia luciliae
      and maintained at 34 +/- 0.5 degrees C. After 5 passages it was adapted to axenic
      cultivation by addition of 0.02% Bacto agar in Diamond's TYI-S-33 medium in place
      of Crithidia. Subcultures or replacement with fresh complete media were done
      twice or thrice for 7 days, after which the agar was omitted and a stable culture
      was obtained. Isoenzyme analysis showed that this strain of E. histolytica
      belonged to the zymodeme II pattern, which is one out of 10 pathogenic zymodemes
      of E. histolytica most commonly found among the virulent strains.

PMID- 8160058
TI  - Host tissue reaction to Gnathostoma malaysiae (Nematoda: Gnathostomidae) in
      Rattus surifer Miller.
AB  - The occurrence of adult Gnathostoma malaysiae in Rattus surifer and R. tiomanicus
      in Malaysia has been reported but there are no known reports on the host tissue
      reactions. This paper reports on the gross pathology caused by G. malaysiae in a
      red spiny forest rat, R. surifer and the tissue reactions caused. A tumor-like
      growth was located on the mid-stomach wall in a female rat captured in Gunung
      Bachock, Kelantan, Malaysia. This growth consisted of four tunnel-like structures
      containing sanguinopurulent fluid and leukocytes and this structure led into a
      central canal. The tissue surrounding the tumor was greatly inflamed and there
      was localized gastritis. The tunnel-like structure was surrounded by dense
      fibrotic tissue. The stomach wall was devoid of superficial epithelium and smooth
      muscle but mucinous glands were present. The midregion of the fibrotic scar
      contained eggs of G. malaysiae which had evoked a strong tissue reaction and were
      surrounded by pus. Blood vessels were empty, dilated and had undergone vasculitis
      and thrombosis.

PMID- 8160059
TI  - Hookworm infection and iron stores: a survey in a rural community in Bali,
      Indonesia.
AB  - A study of the rural population of the village of Belumbang, Province of Bali,
      Indonesia, has been conducted to assess the relationship between intensity of
      hookworm infection (hookworm egg count) and iron stores, hemoglobin level or
      hematocrit. There was a significant negative correlation between serum ferritin
      level and hookworm egg count. However no correlation was found between hookworm
      egg count and hemoglobin level or hematocrit. In a separate analysis the above
      correlation could be shown in male hosts but not in female hosts. It is concluded
      that hookworm infection, even in light infection, can interfere with iron stores,
      but in female hosts this effect might be masked by other factors.

PMID- 8160060
TI  - Mefloquine level monitoring in patients with multidrug resistant Plasmodium
      falciparum on the Thai Myanmar border.
AB  - A total of 42 patients with uncomplicated falciparum malaria who attended the
      malaria clinic in Mae Sot, Tak Province were treated with single oral dose of MSP
      3 tablets (Fansimef, equivalent to 750 mg of mefloquine) concurrently with
      primaquine (30 mg). They all contracted the infection from Cambodia. The aim of
      the study was to monitor the efficacy of MSP 3 tablets for the treatment of this
      highly multiple drug resistant strains of Plasmodium falciparum in this area. Of
      the 39 patients included for efficacy assessment, 13 (33.3%) patients had
      sensitive responses, whereas 15 (38.5%) and 8 (20.5%) had RI and RII types of
      response, respectively. Melfoquine concentrations on Day-3 after treatment in
      patients with sensitive and treatment failure groups were comparable; the
      respective mean (SD) values were 665 (279) and 772 (264) ng/ml.

PMID- 8160061
TI  - Studies on dispersal of malaria vectors in a hilly tract of Koraput District,
      Orissa State, India.
AB  - Dispersal of malaria vectors was studied in a hilltop village in Koraput, a
      highly malarious district of Orissa. Immatures from terraced stream beds and day
      time resting adults from artificially dug pit shelters, distributed centrifugally
      at different distances from the village were sampled. Breeding of Anopheles
      fluviatilis, An. annularis and An. culicifacies was found up to a distance of
      1,700 m. Immature density of An. fluviatilis and An. culicifacies showed a
      negative correlation with the distance, but they were not statistically
      significant. The maximum distance at which An. fluviatilis adult females
      collected was 1,500 m. A significantly negative correlation was observed between
      An. fluviatilis resting females and distance. An. culicifacies adults were
      collected in low numbers even in the nearest pit shelters. No An. annularis was
      recorded from the pit shelters. The present record on the dispersal range of An.
      fluviatilis is estimated to be higher than that reported elswhere in India.

PMID- 8160062
TI  - Lambdacyhalothrin treated bed nets as an alternative method of malaria control in
      tribal villages of Koraput District, Orissa State, India.
AB  - A village scale trial was carried out to evaluate the efficacy of bed-nets
      impregnated with lambdacyhalothrin, at the dose of 0.025 g/m2, in reducing
      malaria transmission in villages of Koraput District of Orissa, India, inhabited
      by tribals. The nets were distributed before peak transmission season. There was
      an overall decline in the parasite rate in all the age groups, six months after
      the supply of impregnated nets while the same increased in control village and in
      a village where untreated nets were supplied. The vector densities (resting and
      man landing) were lower in the treated village as compared to untreated and
      control villages throughout the study period. The reduction in the parasite rate
      was consistent when the reimpregnation was done at six monthly interval and the
      same tend to increase when the gap between the two impregnations was increased to
      one year. Though malaria incidence was reduced, transmission was not completely
      interrupted during the study period, due to outdoor transmission. The
      insecticidal effect of bednets was retained upto six months. Washing of bednets
      by the community did not affect the efficacy. The acceptance and usage was better
      with impregnated nets as compared to ordinary nets.

PMID- 8160063
TI  - The ecology of anopheline mosquitos in northwest coastal Malaysia: larval
      habitats and adult seasonal abundance.
AB  - Collections of anopheline mosquitos were made twice monthly for 13 months from a
      cow-baited trap in two villages, Kampung Permatang Rawa and Sungai Udang Kecil,
      on mainland coastal Penang, Malaysia. Each collection period was six hours from
      sunset. Unquantified larval collections were made regularly in each area.
      Although the villages were only about 50km apart, and each had extensive,
      irrigated rice-fields in its vicinity, the species abundance and the seasonal
      fluctuations differed significantly. In Kampung Permatang Rawa Anopheles sinensis
      and An. peditaeniatus were dominant in prevalence, whereas in Sungai Udang Kecil
      An. indefinitus and An. lesteri paraliae were most common and An. peditaeniatus
      was relatively rare. The rice growing schedules in the two areas differed, but
      there was a moderate correlation between the abundance of several species and the
      rice-growing pattern. There was no correlation at either site with rainfall.

PMID- 8160064
TI  - The ecology of anopheline mosquitos in northwest coastal Malaysia: host
      preferences and biting-cycles.
AB  - The host preferences of eight species of anophelines were studied in two coastal
      Malaysian villages, Kampung Permatang Rawa and Sungai Udang Kecil, by seven 12
      hour catches in each village. Collections were made concurrently from a human
      baited net trap, a cow-baited net trap and by human-bait landing catches.
      Anopheles campestris was attracted almost equally to man and cow, but An. lesteri
      paraliae, An. nigerrimus, An. peditaeniatus, An. sinensis, An. indefinitus, An.
      subpictus and An. vagus showed a strong preference for the cow bait. The human
      bait landing catches were more productive than the human-baited net trap, which
      attracted very few mosquitos. Seven more all-night catches were made at each
      village employing only the cow-baited trap, and the combined data were used to
      plot the biting-cycles of each species at each site. Although the biting-cycles
      at the two localities were in general agreement, there were notable differences.
      At Sungai Udang Kecil, where the collection site was relatively sheltered,
      several species showed a steady decline in numbers from sunset to sunrise. At
      Kampung Permatang Rawa, on the other hand, where the site was more exposed and
      close to the sea, the same species showed a bimodal pattern of activity with an
      early evening peak followed by a decline then a period of increased activity
      before sunrise rising to a second, lesser peak at 0500-0600 hours.

PMID- 8160065
TI  - Laboratory observations on the biology of the phlebotomid sandfly, Phlebotomus
      papatasi (Scopoli, 1786).
AB  - Investigations on the biology of Phlebotomus papatasi were carried out under
      laboratory conditions at 28 +/- 2 degrees C and 80 +/- 1% RH. Fecundity of the
      female varied between 61 and 48 (mean 56.2 +/- 5.46) and the incubation period of
      eggs ranged from 7-9 (mean 7.81 +/- 0.61) days. The developmental duration of
      larvae and pupae varied from 24 to 31 (mean 28.57 +/- 2.71) and 9 to 11 (mean
      10.38 +/- 1.51) days, respectively. The rate of insemination, determined from the
      females that laid fertile eggs, was found to be maximum when the females were
      three days old. Autogeny was observed from female sandflies, emerged from the
      larvae fed on animal liver powder. The duration of first and second gonotrophic
      cycles under ambient conditions was shortest in summer and longest in winter.
      Studies on adult longevity showed that the females fed on mouse blood survived
      for 6 to 27 days (mean 14 +/- 12.5 days).

PMID- 8160066
TI  - Susceptibility difference in two populations of Culex quinquefasciatus Say
      (Diptera: Culicidae) to three synthetic pyrethroids.
AB  - Three synthetic pyrethroids were tested for their efficacy against two
      populations of the filariasis vector Culex quinquefasciatus under laboratory
      conditions following the WHO procedure, Emulsifiable concentration and technical
      grade formulations of deltamethrin (2.5% wp), cypermethrin (1.0% EC) and
      permethrin (25% EC) were employed on the larvae of the said species collected
      from Mysore and Mandya. All the three pyrethroids were found to be effective. But
      among the three, deltamethrin was found to be the most effective and cypermethrin
      was more efficient than permethrin. Mysore species were found to be more
      susceptible than the Mandya population to all the chemicals tested though they
      are separated by hardly 50 km.

PMID- 8160067
TI  - Comparative radular morphology of Lymnaea (Bullastra) cumingiana (Pulmonata:
      Lymnaeidae) and related taxa in the Indo-Pacific region.
AB  - The radular morphology of Lymnaea (Bullastra) cumingiana was compared to that of
      five other Indo-Pacific lymnaeid "species", namely: L. (Radix) quadrasi
      (Philippines), L. (R.) rubiginosa (Indonesia and Thailand) and L. (R.) viridix
      (Guam and Hong Kong) in order to investigate the taxonomic relationship among the
      six species. Although all six species uniformly exhibited a unicuspid, slightly
      asymmetrical central (rachidian) tooth and tricuspid laterals, interesting
      differences were noted among the outer marginals. These were observed to be
      uniquely bicuspid in L. cumingiana, predominantly tricuspid in L. quadrasi,
      tetracuspid in L. rubiginosa (Indonesia and Thailand) and multicuspid in L.
      viridis (Guam and Hong Kong). Thus, the results support the hypotheses that L.
      cumingiana is a unique species compared to the rest, that L. quadrasi is closely
      related to L. rubiginosa (Indonesia and Thailand) and that the two geographical
      isolates of L. viridis have not diverged. Radular morphology was therefore found
      to have a limited significance in elucidating the taxonomic relationship between
      the six groups of lymnaeids studied.

PMID- 8160068
TI  - Comparative shell morphology of Lymnaea (Bullastra) cumingiana (Pulmonata:
      Lymnaeidae) and related taxa in the Indo-Pacific region.
AB  - Comparative shell morphology using both quantitative and qualitative parameters
      was employed to investigate the taxonomic relationship between the endemic
      Philippine species, Lymnaea (Bullastra) cumingiana and five other lymnaeid
      "species" in the Indo-Pacific region, namely: L. (Radix) quadrasi (Philippines).
      L. (Radix) rubiginosa (Indonesia), L. (Radix) rubiginosa (Thailand), L. (Radix)
      viridis (Guam) and L. (Radix) viridis (Hong Kong). Fifty randomly chosen adult
      specimens of each species were studied and compared, although only field
      collected specimens were studied for the first four groups and laboratory-raised
      specimens for the last two group. Results strongly suggested that L. cumingiana
      is a distinct species among the rest. L. quadrasi, L. rubiginosa (Indonesia) and
      L. rubiginosa (Thailand) exhibited great affinity towards each other. Likewise,
      the two geographical isolates of L. viridis were practically identical to each
      other except for some minor size differences.

PMID- 8160069
TI  - Ecological observations on Lymnaea (Bullastra) cumingiana.
AB  - Field surveys conducted at Echague, Isabela and San Pablo, Laguna revealed that
      Lymnaea (Bullastra) cumingiana, the natural second snail intermediate host of
      Echinostoma malayanum in the Philippines, exhibits a moderate degree of diversity
      in its choice of habitats. Rice fields of all stages of development, stagnant
      shallow streams and springs are the main areas where the snail can be collected
      from at Echague, Isabela. However, they were absent in rice fields that had been
      extensively sprayed with molluscicides to control the "golden apple snail"
      (Ampullarius canaliculatus). In contrast, they were also very abundant in the
      highly eutrophic waters of Sampaloc lake, San Pablo, Laguna. L. cumingiana co
      exists with various species of insects, snails, fish and plants in these
      habitats. Information on ecological characteristics affecting its distribution
      will be useful for those who wish to collect and study this species in the
      future.

PMID- 8160070
TI  - Laboratory evaluation of propoxur and fenvalerate against infected and
      noninfected Leptotrombidium fletcheri (Acari: Trombiculidae).

PMID- 8160071
TI  - Parasitic infection and socio-demographic characteristics of urban construction
      site workers.
AB  - The socio-demographic characteristics and prevalence of parasitic infection of
      117 (96 males and 21 females) construction site workers were investigated by
      means of questionnaires and stool examinations. The age characteristics of the
      individuals investigated varied widely from 15-60 years with a high percentage in
      the 21-30 years age range, no sex differences were discovered. Most of the
      workers received primary education even though some of them did not complete it.
      The percentage of illiteracy in females was quite high (9.5%) compared with males
      (2.1%). About 60% and 20% of these construction site workers migrated from the
      northeastern and northern regions of Thailand, respectively. 79.3% of male and
      94.7% of female workers were found to be infected with parasites. Hookworm and
      Opisthorchis were predominant parasites.

PMID- 8160072
TI  - The clinical effects of recombinant human erythropoietin for the treatment of
      anemia in end stage renal disease patients on dialysis.
AB  - It has been widely accepted that recombinant human erythropoietin can improve
      renal anemia which in turn eliminates several complications that occur from
      giving blood transfusions repeatedly in chronic dialysis patients. While there
      are few studies of erythropoietin administration via the subcutaneous route, such
      studies have reported different results from the intravenous route traditionally
      recommended in the literature. We set a cross-over technique to assess the
      results and adverse effects of erythropoietin administered by different routes in
      two groups of our chronic hemodialysis and continuous ambulatory peritoneal
      dialysis patients. The purposes of this study were: 1) to verify the
      effectiveness of erythropoietin; 2) to test whether the subcutaneous route yields
      the same results as the intravenous route and if there is no difference, we will
      choose the former for the benefit and compliance of our patients; and 3) to find
      out any adverse effects.

PMID- 8160073
TI  - A blood pressure profile of rural Kadazans and Bajaus in Sabah, east Malaysia.
AB  - A survey was conducted to document the blood pressures of two indigenous groups
      (Kadazans and Bajaus) who reside in rural Sabah in East Malaysia. Their health
      knowledge status is also recorded. Fifty percent of those surveyed were unable to
      associate high blood pressure with a risk factor and as high as 38% were unaware
      of the consequences of high blood pressure. A total of 16.2% had blood pressures
      > or = 140/or 90mm Hg while 3.9% had blood pressures > or = 160/or 95mm Hg. While
      these figures are low compared to those of developed countries, lifestyle changes
      associated with rapid urbanization in Malaysia may be expected to increase
      hypertension prevalence. The strengthening of health education programs is timely
      as health knowledge is limited and many hypertensives default treatment.

PMID- 8160074
TI  - Congenital syphilitic nephrosis.
AB  - Analysis of congenital syphilis in 455 infants and neonates between 1977-1991 in
      Children's Hospital, Bangkok, Thailand revealed 11 cases (2.4%) with evidence of
      congenital syphilitic nephrotic syndrome which were confirmed by clinical,
      serologic and laboratory findings, long bone x-rays and renal biopsy. Ages of all
      11 cases were between 1 day to 2 months (mean 24 days); 6 were boys and 5 girls.
      Two of them died because of necrotizing enterocolitis and sepsis respectively;
      the mortality rate was 18%. The other nine had complete recovery following
      penicillin therapy.

PMID- 8160075
TI  - Melioidosis in a splenectomized boy with beta-thalassemia major.

PMID- 8160076
TI  - Ocular sparganosis in Thailand.

PMID- 8160077
TI  - Cryptosporidium infection in an immature baby in Indonesia.

PMID- 8160078
TI  - Subcutaneous abscess of neck, a granulomatous reaction to eggs of Paragonimus: a
      case report from northern Thailand.

PMID- 8160079
TI  - [Halo-femoral traction in fractures of the thoracolumbar spine].

PMID- 8160080
TI  - [Personal experience with the areolar rotation technic in surgical treatment of
      gigantomastia].
AB  - The authors present a less commonly used method in reduction and modelling of
      gigantomastia. They draw attention to the advantages of this surgical procedure
      which is based on rotation of the areola with a broad upper and lateral pedicle.
      They emphasize in particular the very good postoperative nutrition of the areolas
      with preservation of their sensitivity.

PMID- 8160081
TI  - [Reduction surgery of the breasts at the Plastic Surgery Clinic in Prague].
AB  - The authors present an account of the history of surgical treatment of
      hypertrophic breasts at the Clinic of Plastic Surgery in Prague. They divided the
      period from 1928 to the present time into stages with regard to the predominating
      technique. The authors emphasize also the necessity of careful selection of the
      surgical procedure with regard to the type and extent of the defect.

PMID- 8160082
TI  - [Therapy of spinocellular carcinoma of the esophagus].

PMID- 8160083
TI  - [Intrapericardial cyst of the pericardium].
AB  - The authors present the case--history of a female patient with an
      intrapericardial cyst in the pericardium which exerted pressure and caused thus
      discomfort to the patient. After extirpation of the cyst via sternotomy the
      patient has no complaints. The authors draw attention to the rare occurrence of
      these cyst in the pericardial cavity and to pitfalls of diagnosis and surgery of
      this located cysts.

PMID- 8160084
TI  - [Conservative surgical treatment of breast carcinoma in women from the viewpoint
      of the oncologist-radiotherapist].
AB  - The authors draw attention to the changed approach to treatment of initial stages
      of breast in women--a change from radical mastectomy to less radical operations
      supplemented by radiotherapy or possibly systemic treatment. They analyze in
      detail the prerequisites and results of this procedure and demonstrate their
      conclusions on a group of 27 women.

PMID- 8160085
TI  - [Surgical therapy of serious heart rhythm disorders].
AB  - The author summarizes his experience with operations in 40 patients. Twenty-one
      were operated on account of W-P-W syndrome, 9 on account of ventricular
      tachycardia due to IHD and in 10 patients an automatic defibrillator was
      implanted. None of the patients died and the results of surgery are satisfactory.

PMID- 8160086
TI  - [Surgical methods in the treatment of retroperitoneal neuroblastoma].
AB  - The authors submit their experience with the surgical treatment of
      retroperitoneal neuroblastoma, which is one of the most frequent solid tumours of
      child age. They describe the principles of the surgical technique with emphasis
      on radical removal of the tumour even in the area of large blood vessels. They
      emphasize the advantage of using an ultrasonic surgical aspirator (CUSA,
      Valleylab Co., Pfizer) which makes it possible to remove residues of the tumour
      without damaging the large blood vessels. During the period between 1987-1992
      they treated at the Motol Faculty Hospital 69 children with retroperitoneal
      neuroblastoma. Of these 60 were operated. In the first stage of the disease 9
      patients were operated, all survive. In the second stage 4 patients were
      operated, 75% survive, in the third stage 24 patients 50% survive, in the fourth
      stage 20 of 29 patients were operated and 11 (38%) survive. In stage IV--S three
      patients were operated, one survives. The total survival of patients during the
      investigation period is 52%.

PMID- 8160087
TI  - [Pseudo-obstruction of the colon (Ogilvie's syndrome) and its significance in the
      differential diagnosis of ileus of the large intestine].
AB  - The authors submit an analysis of a group comprising 33 patients who were in the
      course of two years (1991-1992) hospitalized as emergency cases on account of
      ileus of the large bowel. All patients were subjected urgently in addition to a
      basic clinical examination and a native X-ray of abdomen also to irrigographic
      examination. On its basis in three patients the diagnosis of pseudoobstruction of
      the large intestine-Ogilvie's syndrome was established. These three patients were
      successfully treated by a conservative approach. The author summarizes data from
      the literature pertaining to this disease and confronts them with his own
      clinical observation. He draws attention to the fundamental importance of
      irrigography for the differential diagnosis in patients admitted with sings of
      obstruction of the colon.

PMID- 8160088
TI  - [Acute terminal ileitis and Crohn's disease].
AB  - The finding of acute inflammation of the terminal ileus frequently leads to
      differential diagnostic reflections whether it is the first stage of Crohn's
      disease or acute ileitis with a different aetiology. At the Surgical Clinic of
      the Third Medical Faculty in Prague 10 in 1981-1992 21 patients with this
      condition were hospitalized and operated. Crohn's disease developed subsequently
      only in six patients and in five of them the development of the disease called
      for another operation. The remaining 15 patients are free from clinical
      complaints. The mean age of these patients at the time of operation was 30.4
      years, the mean length of the gut affection was 9.7 cm, the mean follow up period
      is 6.4 years. The author analyzes possible causes of these cases of ileitis and
      discusses the relationship with Crohn's disease.

PMID- 8160089
TI  - [Postgraduate education in surgery in Belgium].

PMID- 8160090
TI  - [100 renal transplantations with intravesical implantation of the ureter].
AB  - Transplantation of the kidney is nowadays a common therapeutic method. During the
      past 30 years in the transplantation centre of IKEM more than 1200
      transplantations were performed. The authors present a group of 100 patients
      where the ureter of the transplanted Kidney was attached to the urinary bladder
      of the recipient by intravesical technique. With regard to the low incidence of
      fistulas and the easy solution of complications this technique can be widely used
      in clinical transplantation programmers.

PMID- 8160091
TI  - [Special features of anesthesia during surgery for acquired heart valve defects].
AB  - The authors describe some special features as regards anesthesia with large
      opioid doses in patients operated on account of acquired valvular disease. They
      emphasize in particular the importance of adequate knowledge of
      pathophysiological changes associated with the damage of different orifices and
      their interpretation in the anaesthesiological procedure which is the basis of
      its success. In the conclusion the authors describe basic haemodynamic changes in
      combined simultaneous affection of several valves.

PMID- 8160092
TI  - [Radiation tolerance of the human spinal cord].
AB  - PURPOSE: Chronic myelopathy is among the most serious sequelae of high dose
      radiation treatment. Therefore medical and forensic reasons warrant detailed
      knowledge of the radiation tolerance of the human spinal cord. PATIENTS AND
      METHODS: This paper reviews published data on the incidence of radiation
      myelopathy in patients treated with megavoltage radiation. RESULTS AND
      CONCLUSIONS: Two years after completion of radiation treatment with daily
      fractions of approximately 2 Gy development of radiation myelopathy is expected
      in 1% of the patients at 50 to 55 Gy. An incidence of 5% is estimated to occur at
      approximately 55 to 60 Gy. At higher doses the risk of spinal cord damage
      increases steeply. Interpretation of these data has to consider that the
      incidence of radiation myelopathy increases with increasing time of follow-up.
      Even after two years no clearcut plateau is observed. High doses per fraction are
      poorly tolerated by the spinal cord, the alpha/beta-ratio appears to be
      approximately 1 Gy. Accelerated schedules with < or = 2 Gy per fraction but daily
      doses greatly exceeding 2 Gy may result in a higher risk of radiation myelopathy
      than conventionally fractionated treatments. This observation seems, at least in
      part, to be due to a slow component of repair of sublethal radiation damage in
      the spinal cord.

PMID- 8160093
TI  - Incidence of second solid cancer in patients after treatment of Hodgkin's
      disease.
AB  - PURPOSE: An analysis of the incidence of second malignant solid tumors in our
      patients after radiotherapy or radiotherapy plus chemotherapy for Hodgkin's
      disease has been performed. PATIENTS AND METHODS: 340 patients had curative
      treatment with mantle or paraaortic and pelvic radiotherapy (1964 to 1972) or
      mantle plus paraaortic and spleen or splenic pedicle or total nodal radiotherapy
      with or without chemotherapy (1973 to 1992) and have a follow-up of at least 1.5
      years. Since 1987, after chemotherapy only modified involved fields were
      irradiated. All second tumors have been histologically verified. The cumulative
      incidence of second solid cancer of the patients have been compared with the age
      and sex specific expected rates according to the "Zurcher Krebsregister 1980 to
      1990". RESULTS: We observed seven patients with leukemia after radiotherapy plus
      chemotherapy, five patients with non-Hodgkin-lymphoma and 21 patients with solid
      cancers after radiotherapy or radiotherapy and chemotherapy with a cumulative
      risk of all second malignancies of 7.0% (ten years), 30.7% (20 years) and 40.5%
      (24 years). Cumulative risk of second solid cancer was 3.1% (ten years), 9.3% (15
      years), 23.5% (20 years) and 34.3% (24 years). Cumulative risk of second solid
      cancer was significantly higher than expected with no decrease of the relative
      risk after more than 20 years of follow-up. Comparable to the observations from
      Stanford, we observed a significantly higher risk of breast cancer in women less
      than 30 years of age at treatment. Relative risk of second solid cancer was
      higher after radiotherapy plus chemotherapy compared to radiotherapy alone, but
      the difference was not statistically significant. Nearly all patients with
      radiotherapy plus chemotherapy and a follow-up of ten years or more had
      radiotherapy with large fields. CONCLUSIONS: In patients after treatment of
      Hodgkin's disease with radiotherapy or radiotherapy plus chemotherapy, incidence
      of second solid cancer is significantly higher than expected. Incidence of second
      solid cancer after chemotherapy and large field radiotherapy is higher than after
      radiotherapy alone, but this difference is statistically not significant.

PMID- 8160094
TI  - [Quality assurance of interstitial irradiation in the breast-conserving therapy
      of breast cancer].
AB  - PURPOSE: The purpose of this communication is to describe the procedure of
      interstitial implant planning in definitive irradiation of early breast cancer.
      There are some reports about localization techniques of the boost volume for
      external irradiation. Less has been reported about the target volume localization
      of HDR implants of the breast. METHODS: Conservative surgery and following
      radiation therapy have become a standard treatment in the management of early
      breast cancer. The use of a boost irradiation in the area of the primary tumour
      seems to be promising in decreasing local recurrence rates. Most of our patients
      received a boost dose by interstitial HDR iridium-192 therapy. Therefore we have
      improved the method of interstitial implantation by CT under general anesthesia.
      The implant is planned in the simulator room by localizing the radiopaque clips
      of the tumor bed, the entrance and exit points of the needles are determined by
      marking the skin. Then the implantation is done in the operating and afterloading
      room. A device for patient transportation between brachytherapy unit and CT has
      been constructed. So patients can be shifted under general anesthesia between the
      different devices without any problems. The implanted needles and the clips are
      visualized by the means of CT. The target volume can be defined and the source
      dwell positions determined. CONCLUSION: This method improves the accuracy of
      target localization. Therefore the treated volume can be adapted and minimized,
      resulting in less side effects and may contribute to maximize local control.

PMID- 8160095
TI  - [Preventive percutaneous radiotherapy for avoiding hyperplasia of the intima
      following angioplasty together with stent implantation].
AB  - PURPOSE AND BACKGROUND: Interventional radiologic procedures play an important
      role in the management of peripheral arterial occlusive disease. Percutaneous
      transluminal interventions as angioplasty (PTA) and implantations of metal-stents
      injure the wall of the blood vessels resulting in hyperplasia of the intima and
      media. In spite of adequate anticoagulation therapy restenosis and reocclusion
      frequently occur. Our study was designed to prevent hyperplasia of the intima by
      percutaneous radiation therapy. PATIENTS AND METHODS: A total of 24 patients had
      a stent implanted in their superficial femoral artery from 1990 to 1992. Eleven
      patients received percutaneous radiation therapy of the enlarged stent area on
      five consecutive days with a single dose of 2.5 Gy thus resulting in a total dose
      of 12.5 Gy. Both patients groups were compared. None of the patients in the
      radiation group suffered from complications. RESULTS: In the seven months
      following stent implantation and radiation only two of eleven patients in the
      radiation group suffered from occlusion of the stent that had to be treated by
      vascular surgery. In comparison five of 13 patients treated with stent
      implantation alone suffered from occlusion of the stent within the first eight to
      nine months. CONCLUSION: In spite of a small case number our study shows a
      positive influence of percutaneous radiation therapy on the extent of hyperplasia
      of the intima after stent implantation leading to lower reocclusion rates.
      Whether these results can be improved by alternative dose-fractionation schedules
      has to be addressed by further studies.

PMID- 8160096
TI  - Radiation therapy for brain metastases from lung carcinoma. Prospective
      randomized trial according to the level of lactate dehydrogenase.
AB  - PURPOSE: Since September 1980 we have been conducting a prospective randomized
      trial to determine the best treatment schedule for radiation therapy (XRT) on
      brain metastasis from lung carcinoma. The first trial (September 1980 to December
      1984) was randomly allocated by two different time-dose radiotherapy schemes,
      i.e., 30 Gy/ten fractions/two weeks versus 50 Gy/20 fractions/four weeks.
      Treatment results showed no significant difference in neurological improvement
      and survival between the two arms and lactate dehydrogenase (LDH) as the most
      important prognostic factor. The present study (January 1985 to April 1992)
      examines two sequential trials stratified by the level of LDH enrolled 162
      patients with brain metastasis from lung carcinoma. PATIENTS AND METHODS: Whole
      brain dose was selected for 30 Gy/ten fractions/two weeks (group A, n = 46) or 50
      Gy/20 fractions/four weeks (group B, n = 46) in the group with normal LDH and 30
      Gy/ten fractions/two weeks (group C, n = 35) or 20 Gy/five fractions/one week
      (group D, n = 35) in the group with high LDH, while the treatment fields were
      shrunk at 30 Gy in group B if possible. RESULTS: The final results showed the
      facts that 1. the most important prognostic factor, according to Cox's
      multivariate analysis, was also the level of LDH in the second trial, 2. the
      incidence of acute side effects showed the trend toward depending upon a single
      dose, i.e., group A (3 Gy/fraction); 35% versus group B (2.5 Gy/fraction); 21% (p
      = 0.165) and group C (3 Gy/fraction); 23% versus group D (4 Gy/fraction); 45% (p
      = 0.044), 3. median survival time and one-year survival rates were 5.4 months and
      21% in group A; 4.8 months and 17% in group B; 3.4 months and 6% in group C; and
      2.4 months and 4% in group D, respectively, and survival curves showed no
      statistically significant difference between the two treatment groups in each LDH
      group, 4. improvement in neurologic function appeared to increase with total
      dosage escalation, i.e., 41% in group A versus 45% in group B and 35% in group C
      versus 21% in group D (p = 0.13). CONCLUSION: A short course (30 Gy/ten
      fractions/two weeks) is an advantageous XRT because of the short treatment time
      for normal LDH and neurological improvement and minor toxicity for the high LDH
      group, while an optional treatment may be necessary for the selected patients.

PMID- 8160097
TI  - [How do patients experience radiotherapy?].
AB  - PURPOSE: In the course of a radiotherapy treatment oncological patients--in
      addition to some physical symptoms--often experience severe psychological
      distress. This study assesses and analyses the psychological strains emerging
      throughout a radio-oncological treatment. Specific intervention measures are
      being suggested to alleviate patient's psychosocial distress. This study is part
      of a psychosocial intervention project performed in a radio-oncological
      department. PATIENTS AND METHODS: Using a semi-standardised interviewing
      technique 30 radio-oncological in-patients were questioned in depth about their
      psychosocial situation. Subsequently a fully standardised written questionnaire
      was designed, enabling a further 150 patients to be investigated retrospectively,
      when presenting themselves for routine radio-oncological follow-up examinations.
      RESULTS: In particular, the irradiation session itself, the waiting time
      beforehand, and the relationship to fellow patients were found to be potentially
      stressful. More than half of all patients reported anxiety during their first
      irradiation, which usually decreased during subsequent sessions, and in no case
      increased. One third of the 30 inpatients wished to have more contact and
      conversations with fellow-patients, e.g. while waiting for their treatment. The
      150 retrospectively assessed patients stated a substantially lower wish for
      further contact. Almost one third of the in-patients apparently gained comfort
      from a downward comparison to patients who they perceived as being worse off than
      themselves. CONCLUSION: Psychosocial intervention can help radiotherapy patients
      to cope with fears and distress, and thus enhance their quality of life. Support
      should be provided by psychological specialists, as well as by clinical staff in
      various ways. Anxiety concerning radiotherapy can often be alleviated through a
      sensitive and empathetic manner while explaining the radiotherapy process.
      Patient groups and seminars offer patients the opportunity to exchange
      experiences and to gain further information about their disease and treatment. In
      situations of extreme distress psychologists can accompany patients, and if
      necessary perform crisis intervention. Psychological specialists can also provide
      further education and support for the clinical staff.

PMID- 8160098
TI  - Use of surface markers for MR radiotherapy planning.
AB  - PURPOSE: For the precise planning of radiotherapy treatment ports, the
      delineation and control of their borders has to be performed with X-ray and other
      imaging procedures before and during the therapy. MATERIALS AND METHODS:
      Conventional planned therapy ports are checked with the help of MR-imaging with
      new gel-markers, as a further development to formerly used fluid filled tubes, on
      the skin of the patient in different regions. We describe the essentials of these
      gels and report about their first practical use. RESULTS: Principal
      considerations to the technique and practical applications are given with imaging
      examples. The essential physical qualities of the gels are introduced with
      separate NMR experiments. It turns out, that multiplanar MR-imaging in
      combination with field markers on the skin is a fast simple and useful help for
      the control and the improvement of treatment planning. CONCLUSION: MR-imaging
      with gel-markers on the skin in many cases can show the tumor and the field-ports
      in one picture. Thus the therapy planning is refined with simple means. On the
      one hand the target volume can be seized completely and on the other hand
      sensitive organs can better be protected.

PMID- 8160099
TI  - [Dosimetry using pyromellitic acid and trimellitic acid. Part 1].
AB  - PURPOSE: The intention of the study was to demonstrate that a chemical dosimeter
      on the basis of fluorescing acids is able to measure ionizing radiation much more
      sensitively than the Fricke dosimeter. MATERIALS AND METHODS: As detectors for
      ionizing radiation pyromellitic acid (1,2,4,5-benzene-tetracarboxylic acid) and
      trimellitic acid (1,2,4-benzene-tricarboxylic acid) were investigated. Both
      solutions were exposed to pulsed 10 MV photons. The dose rate and the radiation
      dose were modified according to the different questions. RESULTS: The correlation
      between absorbed dose and intensity of fluorescence was studied from 2 Gy up to
      doses of 16 Gy. Within this dose range the intensity of fluorescence of the
      mentioned solutions correlate with the absorbed doses in a single-valued and
      linear way. The fluorescence of pyromellitic acid is independent of the dose rate
      in the studied range from 0.6 Gy/min to 5 Gy/min. Detectors with trimellitic acid
      are able to quantify the absorbed energy of ionising radiation independent of the
      dose rate from 0.6 Gy/min on, but in contrast to pyromellitic acid only up to 3.8
      Gy/min. The stability of the excitation and fluorescence spectra, the fading of
      the irradiated detectors, the reproducibility of the measured results and the
      increase of the null value of both solutions qualify for the use of these
      dosimeters in the clinical routine. CONCLUSIONS: If further measurements should
      prove the independence of the presented detectors from the kind of radiation, the
      radiation quality and the temperature, there is a new possibility to use the
      specific advantages of chemical dosimeters in a more simple way.

PMID- 8160100
TI  - [Does leucovorin increase the cardiotoxicity of 5-fluorouracil?].

PMID- 8160101
TI  - [Is mitomycin C necessary in the radiochemotherapy of anal canal cancer?].

PMID- 8160102
TI  - [Does the interval between organ preservation breast surgery and the following
      definitive radiotherapy influence the prognosis?].

PMID- 8160103
TI  - [Successful therapy of lymphedema].

PMID- 8160104
TI  - [Multisegmental electron irradiation of the thoracic wall following ablative
      therapy of breast cancer].

PMID- 8160105
TI  - [Radiotherapeutic indications in benign diseases. On the paper by KR Trott:
      Therapeutic effects of low radiation doses].

PMID- 8160107
TI  - Complications of blepharoplasty.
AB  - Although blepharoplasty is a technically straightforward procedure, many
      postoperative complications may occur. Some of the untoward effects may be only a
      transient nuisance for the patient, such as mild ocular dryness, whereas other
      sequelae can lead to severe visual loss. An extensive review of the prevention,
      diagnosis, and management of complications associated with blepharoplasty is
      presented.

PMID- 8160106
TI  - Introducing "public health and the eye".

PMID- 8160108
TI  - Cortical visual impairment in children.
AB  - Cortical visual impairment (CVI) in children is most commonly caused by peri- or
      post-natal hypoxia-ischemia, but may also occur following other insults, e.g.,
      trauma, epilepsy, infections, drugs or poisons, and certain neurologic diseases.
      The disorder differs considerably in etiology, physical findings, and, perhaps,
      prognosis, from the cortical blindness seen in adults. The same event that causes
      CVI by damaging the geniculate and/or extrageniculate visual pathways may also
      damage other areas of the brain, or the retina, optic nerves, or chiasm. Thus,
      children with CVI often have other neurological problems. Diagnosis may require
      the participation of a multidisciplinary team and the use of special visual
      testing techniques. Due to the uncertainty concerning the prognosis in CVI,
      clinicians should remain optimistic about the child's potential for some vision
      recovery.

PMID- 8160109
TI  - Bilateral visual loss and disc edema in a 15-year-old girl.
AB  - A 15-year-old girl with a ventriculoperitoneal shunt for congenital hydrocephalus
      presented with bilateral visual loss and disc edema. Although a CT scan showed no
      change in ventricular size, subsequent evaluation revealed elevated intracranial
      pressure and shunt malfunction. Initial visual loss was secondary to chronic
      papilledema. The rapid reduction of longstanding elevated intracranial pressure
      may have contributed to worsening of visual function after shunt revision.
      Subsequent optic nerve sheath fenestration did not improve visual function. In
      patients with treated hydrocephalus and symptoms of signs of raised intracranial
      pressure, shunt malfunction should be suspected even if neuro-imaging proves
      unremarkable.

PMID- 8160110
TI  - Orbital lymphoma associated with acquired immune deficiency syndrome (AIDS).
AB  - A new case of AIDS-associated, small noncleaved cell (Burkitt's) lymphoma that
      presented as an orbital mass is described. Extraocular muscle involvement was
      documented by computed tomography and confirmed by orbital biopsy. Extensive
      abdominal involvement was subsequently diagnosed and this caused the patient's
      death only 15 days after the initial consultation and orbital biopsy. A
      literature review discloses only eight previous case reports of AIDS-associated
      non-Hodgkin's lymphoma (NHL) involving the orbit: two cases of Burkitt's type and
      six cases of large cell immunoblastic type. Three additional cases of orbital NHL
      can be found among larger series of AIDS cases. Affected patients are uniformly
      young adult males with a history of homosexuality and/or IV drug abuse.
      Variations in clinical presentation are discussed. Although the morphology of the
      histopathologic specimen in our case was consistent with a high-grade, small
      noncleaved cell NHL, flow cytometry revealed an atypical immunophenotype for
      Burkitt's lymphoma in that CD20 and immunoglobulin light chain antigens were not
      expressed. Morphologic classification and immunophenotypic characteristics of
      AIDS-associated NHLs are discussed.

PMID- 8160111
TI  - Chiasmal trauma: clinical and imaging considerations.
AB  - This report presents a patient who sustained closed head injury with chiasmal
      trauma. This uncommon injury may not be apparent on routine imaging studies. It
      is significant, not only from the visual standpoint, but also because of the
      association with serious conditions, such as panhypopituitarism, traumatic
      carotid aneurysm, carotid cavernous fistulae, and meningitis associated with
      leakage of cerebrospinal fluid. This report demonstrates that magnetic resonance
      imaging (MRI) is the best method for identifying chiasmal abnormalities.

PMID- 8160112
TI  - Origins and evolution of the Lancaster Course in ophthalmology.
AB  - The Lancaster Course was created in 1945 to meet a need for training in the basic
      sciences of ophthalmology. At that time the course was designed particularly for
      young physicians who were discharged from the Armed Services at the end of World
      War II. For nearly five decades, the course has been given each summer at Colby
      College in Waterville, Maine, with the participation of some of the most
      illustrious figures in ophthalmology. It has undergone numerous changes in
      faculty and student body, having become less directed toward the experienced
      physician and more toward the beginning resident. What has not changed in the
      informal environment combined with intensive study, which allows students to
      learn basic sciences and to interact with outstanding leaders in ophthalmology.

PMID- 8160113
TI  - Acquired ocular visual impairment in children, 1960-1989.

PMID- 8160114
TI  - Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular
      toxicity: a prospective study of 63 patients.

PMID- 8160115
TI  - Thrombospondin as a component of the extracellular matrix of epiretinal
      membranes: comparisons with cellular fibronectin.

PMID- 8160117
TI  - [Gravel in the engine. Interview by Teddy Osterlin Koch].

PMID- 8160116
TI  - Duane's retraction syndrome and arthrogryposis multiplex congenita.

PMID- 8160118
TI  - [Prevention--know your breast].

PMID- 8160119
TI  - [Quality assurance--the good apples. Interview by Kirsten Bjornsson].

PMID- 8160120
TI  - [Quality assurance--good practice. Interview by Kirsten Bjornsson].

PMID- 8160121
TI  - [EEC's Year of the Aged. Health care for the aged could be better].

PMID- 8160123
TI  - [Illegal transplantations].

PMID- 8160122
TI  - [Solidarity raised].

PMID- 8160124
TI  - [Greece. Many kind of nurses. Interview by Mette Fjordbo].

PMID- 8160125
TI  - [Greece. Small in engagement].

PMID- 8160126
TI  - [Agreement is here--why not use it?].

PMID- 8160127
TI  - [Clinical nursing--ulcerative colitis].

PMID- 8160128
TI  - [Ulcerative colitis--chronically ill and vulnerable].

PMID- 8160129
TI  - [Ward management--one of the busiest].

PMID- 8160130
TI  - [Continuing education--support for education and reform].

PMID- 8160131
TI  - [Greece. Between doctors and family].

PMID- 8160132
TI  - [We miss the Danish students].

PMID- 8160133
TI  - [County administration election--an exciting chair. Interview by Soren Palsbo].

PMID- 8160134
TI  - [Greenland's education is ready. Interview by Soren Palsbo].

PMID- 8160135
TI  - [The problems of collagen formation in chronic liver diseases].
AB  - With employment of radioimmunoassay, the level of procollagen-III-peptide was
      measured in the blood of 71 patients with chronic hepatic diseases versus 20
      healthy controls. This level was examined for correlation with characteristics of
      the etiological factor, the degree of hepatic-cellular inflammation and immune
      reactions. Procollagen-III-peptide concentrations were directly correlated with
      transaminases and reversely with activity of antibody formation. Collagenopoiesis
      gained intensity in the range from chronic persistent hepatitis to hepatic
      cirrhosis. Virus infection and alcohol are among the most potent etiological
      factors stimulating collagenopoiesis. The least procollagen levels occurred in
      hepatic diseases obscure in origin.

PMID- 8160136
TI  - [Porphyrin metabolism in chronic liver diseases].
AB  - Out of 147 patients with chronic hepatic diseases, chronic persistent hepatitis,
      chronic active hepatitis, hepatic cirrhosis, alcoholic lesions of the liver,
      biliary hepatic cirrhosis and Gilbert syndrome were registered in 26, 35, 27, 43,
      8 and 8 patients, respectively. Urinary and fecal porphyrins were measured
      spectrophotometrically. Disturbances in porphyrin metabolism were diagnosed in 76
      patients (51.7%). Four different biochemical syndromes were identified: 1) a
      symptomatic rise of fecal porphyrins only, 2) secondary coproporphyrinuria, 3)
      secondary coproporphyrinuria in combination with high fecal protoporphyrin, 4)
      biochemical syndrome of chronic latent hepatic porphyria. These syndromes were
      not strictly specific, but secondary coproporphyrinuria occurred significantly
      more often in chronic active hepatitis and biliary cirrhosis. High symptomatic
      fecal porphyrins were characteristic for alcoholic affections, and latent hepatic
      porphyria was indicative of hepatic cirrhosis. Disturbed porphyrin metabolism
      arises in more severe hepatic lesions and runs in association with more rapid
      development of hepatocellular insufficiency. Probable pathochemical mechanism and
      diagnostic value of the above impairment are discussed.

PMID- 8160137
TI  - [The use of reaferon in treating patients with protracted viral hepatitis].
AB  - The paper reports the results of a randomized clinicoimmunological trial of
      domestic recombinant alpha 2-interferon (reaferon) in 30 patients with protracted
      viral hepatitis (27 subjects had viral hepatitis B and 3 patients HBV + HDV
      coinfection). The reaferon treatment started on the disease week 7-8 and lasted
      for 2 months (1 x 10(6) IU, once a week, i.m.). VHB patients benefited from
      reaferon treatment as evident from improved clinical and laboratory indices,
      cases of complete cure and the agent elimination. In a protracted course of HBV +
      HDV coinfection reaferon in the above doses failed to produce any effect.

PMID- 8160138
TI  - [The combined treatment with prednisolone and recombinant alpha 2-interferon of
      patients with chronic hepatitis B: the factors influencing the immune response].
AB  - The study included 39 patients with chronic HBeAg and DNA HBV-positive hepatitis
      B. 18 patients received combined therapy with prednisolone and recombinant
      interferon. Pretreatment investigations involved assessment of the basic virus
      replication by HBeAg, IgM anti-HBc, RPSHA titers, of DNA HBV concentration,
      alanine aminotransferase activity. The serum was examined for antibodies to alpha
      2-interferon using enzyme immunoassay. The treatment resulted in disappearance of
      HBeAg in 70.6% of the examinees, DNA HBV in 66.6% of them. AlAT activity returned
      to normal in 58.8% of the patients. HBeAg and HBsAg were not registered in 5.6%
      of the patients. In 2 out of 4 nonresponders antibodies to alpha 2-interferon
      were absent. It is shown serologically that patients with initially low HBeAg,
      DNA HBV, high activity of AlAT, high titers IgM anti-HBc, no antibodies to alpha
      2-interferon have the most favourable prognosis of the hepatitis.

PMID- 8160139
TI  - [The use of an ozonized sorbent in treating patients with progressive pulmonary
      tuberculosis combined with hepatitis].
AB  - After analyzing comparative data on various treatments for progressive pulmonary
      tuberculosis combined with hepatitis, it is inferred that ozonized sorbent
      hemocarboperfusions are effective modality against the above condition. Ozone
      does not activate lipid peroxidation in blood, while it might activate
      electrochemical blood oxidation on the sorbent membrane and produce a direct
      therapeutic effect on hepatocytes.

PMID- 8160140
TI  - [The frontlines of hepatology].

PMID- 8160141
TI  - [The differential diagnosis of focal formations in the liver by using
      ultrasonography].
AB  - The results of hepatic ultrasonography were analyzed for 460 patients who had
      been treated surgically for cancer of the rectum. These were compared to
      histological evidence on the removed macropreparation and on intraoperative
      revision of the liver. Six types of the metastases were recognized to facilitate
      differential diagnosis of cancer with benign hepatic tumors, abscesses and focal
      fat dystrophy. Ultrasound semiotics of hemangioma, abscess, hepatic cyst is
      presented. Ultrasound accuracy in diagnosis of hepatic metastases reached 95%. It
      is shown that metastases of the same tumor type have different structure which
      may be related to the tumor histology and duration of the disease.

PMID- 8160142
TI  - [Seasonal changes in the lipid composition of the bile in Evens and Evenki].
AB  - Altogether 156 Evenks and 162 Evens were examined in the reindeer regions of
      Evenkia and the Yakut Republic located in the extreme north of Russia. Seasonal
      changes in the concentration and ratio of bile lipids were discovered. The
      conclusion is made that space and time coordinates are of importance for the
      diagnosis and treatment of biliary tract diseases in northern nations.

PMID- 8160143
TI  - [The characteristics of duodenogastric reflux in peptic ulcer and chronic
      gastritis].
AB  - Patients with gastroduodenal ulcer, chronic gastritis (CG) and healthy controls
      (124, 57 and 24 subjects, respectively) were examined for intensity and duration
      of duodenogastric reflux (DGR). These indices were assessed by concentrations of
      gastric juice bilirubin. It is found that DGR occurred in 29% of the examinees
      free of gastroduodenal diseases, does not correlate with morphological CG-induced
      changes and Helicobacter pylori contamination degree. The reflux in CG seems to
      be secondary in pathogenesis of this disease. In patients with aggravated
      duodenal and gastric ulcer the reflux in the basal stage is 2-2.5 and 5-6 times
      higher than in the controls, respectively. DGR parameters correlated with the
      height of the ulcer defect. Retrograde entrance of the duodenal content into the
      stomach in duodenal ulcer enhances acid production in the stomach through gastrin
      mechanisms.

PMID- 8160144
TI  - [The pharmacodynamic and ulcer-healing action of modern anti-ulcer agents].
AB  - In a study of 159 duodenal ulcer patients the authors studied the effect of H2
      blockers, antibacterial and sucralfate monotherapy on the frequency of the ulcer
      healing, Helicobacter pylori (HP) infection and acid-proteolytic aggression in
      the body and antropyloric portion of the stomach. All the drugs were found to
      exhibit similar antiulcer activity. Inhibition of the acid-proteolytic aggression
      in the gastric body was registered only under the action of H2-blockers.
      Antibacterial preparations inhibited the growth of HP, but did not affect the
      acidity and proteolysis in the gastric body. Neither did sucralfate which also
      had no effect on microorganisms. All the test drugs were able to reduce
      antropyloric acidity, thus promoting healing of the ulcer.

PMID- 8160145
TI  - [The clinico-histochemical validation of the differential use of calcium
      antagonists in gastroduodenal ulcers].
AB  - A therapeutic effect of selective calcium antagonists is more evident in older
      patients with peptide ulcer and under differentiated administration: verapamil is
      indicated for mediogastric ulcer, nifedipine and diltiazem are better for
      pyloroantral and duodenal ulcer defect. Responses in ulcer patients may be due to
      the drugs positive action on ulcer-induced disturbances in the neuromediator
      processes running in gastroduodenal mucosa.

PMID- 8160146
TI  - [The prevalence, risk factors and secondary prevention of digestive tract
      diseases in workers of the gas-producing industry].
AB  - The examination of the Ukrburgas corporation employees revealed gastrointestinal
      diseases in 107 of them (18.4%): ulcer in 28 and chronic gastroduodenitis in 79
      subjects. The above disorders proved dependent on occupational, social and risk
      factors. Prophylactic antirecurrence courses are recommended for such patients.

PMID- 8160147
TI  - [Organizational principles in preventing diseases of the large intestine taking
      into account epidemiological experience].

PMID- 8160148
TI  - [A case of common variable immunodeficiency in monozygotic twins].

PMID- 8160149
TI  - [The effect of neoton on the course of unstable angina].

PMID- 8160150
TI  - [The determination of catalase activity in chronic alcoholics].

PMID- 8160151
TI  - [Circulating complexes of plasma fibronectin (fibronectin-fibrin) in human
      diseases].
AB  - The study of circulating complexes fibronectin-fibrin in 21 patients with
      immunocomplex affections revealed their high levels which occurred in inverse
      relationships with fibronectin concentrations in the blood, but in direct
      correlation with indicators of inflammation (fibrinogen, cialic acid). It is
      suggested that the complexes are involved in the development of fibrosis at the
      sites of chronic inflammation in immune disorders.

PMID- 8160152
TI  - ["Essential" phospholipids in hepatology (experimental and clinical tests)].

PMID- 8160153
TI  - [Doppler sonography and the possibilities for its use in hepatology].

PMID- 8160154
TI  - [The current aspects of the pathogenesis, clinical picture and treatment of
      cholestasis].

PMID- 8160155
TI  - [Reflux disease: the concept, clinical manifestations, diagnosis and treatment].

PMID- 8160156
TI  - [The role of the vascular endothelium in regulating renal hemodynamics].

PMID- 8160157
TI  - [The treatment of acute promyelocytic leukemia with retinoic acid].

PMID- 8160158
TI  - [The comparative characteristics of hepatitis A and B based on the data from
      clinical and biochemical studies].

PMID- 8160159
TI  - [Constipation and diarrhea].

PMID- 8160160
TI  - [Infectious causes of diarrhea in Central Europe].
AB  - In this paper the most isolated endemic and imported pathogens of diarrhea in
      Central Europe are demonstrated. Clinical symptoms, diagnosis and therapy and
      additional hygiene measures are described.

PMID- 8160161
TI  - [Epidemiology, clinical aspects, prevention and self care in travelers'
      diarrhea].
AB  - Travellers' diarrhea is the most frequently occurring health problem in
      travellers to tropical and subtropical regions. The main risk factors for this
      condition are substandard hygiene, contaminated food and drink. Usually the
      illness begins during the first week of travel and lasts on average four days
      with mild symptomatology. The causative agent is usually bacterial (40%
      enterotoxic E. coli), and strict observance of hygiene rules and careful
      selection of food and drink is an effective strategy to avoid travellers'
      diarrhea. Prophylactic use of antibiotics is rarely indicated, but self-therapy
      is of central importance. Adequate oral rehydration is essential, and in
      uncomplicated cases, antimotility drugs can provide adults with rapid symptomatic
      relief. Additional antibiotic treatment can be recommended.

PMID- 8160162
TI  - [Diagnostic guidelines in diarrhea].
AB  - Acute diarrhea is usually short-lasting; therefore, diagnostic procedures are
      mainly concerning the degree of dehydration. With longer duration of high fever
      or bloody diarrhea, microbiologic stool tests are necessary. Proctosigmoidoscopy
      is indicated in case of dysenteric disease or suspected antibiotic-as-associated
      pseudomembranous colitis. In chronic diarrhea, the most important diagnostic
      procedure is a careful history. Side effects of drugs and food-related causes are
      especially noticeable, as are indices of an organic origin, e.g. unwanted weight
      loss or blood in the stools. Also, careful history and physical examination are
      essential for the decision about laboratory tests, tests of gastrointestinal
      function or endoscopy.

PMID- 8160163
TI  - [Therapeutic guidelines in diarrhea].
AB  - In acute diarrhea water and electrolyte losses are compensated for by oral or
      intravenous rehydration. Oral rehydration solutions contain primarily glucose or
      glucose polymers and sodium as well as other electrolytes. In acute and chronic
      diarrhea, loperamide is the most potent and safe antidiarrheal drug. Antibiotics
      are used without hesitation only in invasive diarrhea. In chronic diarrhea,
      diagnostic work up must precede therapy. Potentially diarrheogenic drugs or foods
      have to be eliminated. In most cases, when the diagnosis has been established,
      specific therapeutic measures are available.

PMID- 8160164
TI  - [Diagnostic strategy in constipation, including irritable bowel syndrome].
AB  - Constipation is not a disease but a symptom. Underlying causes include side
      effects of drugs, metabolic, endocrine, neurologic, psychiatric and intestinal
      diseases. Constipation is part of the so-called irritable bowel syndrome. The
      diagnosis is based on history, physical examination and a few laboratory tests.
      Second-line diagnostic procedures include endoscopy, colonic transit time and
      physiological investigations of the anorectum like anorectal manometry or
      defecography.

PMID- 8160165
TI  - [Therapeutic strategy in constipation].
AB  - Therapy of constipation is complex. It is mainly based on general rules and
      treatment with dietary fibres. If drugs are necessary they should be applied
      according to the type of constipation as evidenced by the results of special
      diagnostic procedures. Surgical treatment is only the last choice. The aim of
      therapy is to relieve the patient from his symptoms and achieve a habit of
      regular defecation, if possible without the application of laxatives. The
      foremost problem in the treatment of constipation is to interrupt the vicious
      circle 'constipation/abuse of laxatives.' Many patients only consult a physician
      when they are already in that problem. Therapy then becomes difficult.
      Information on bowel movements and on how to prevent constipation by the way of
      living, therefore, should be widely spread in the general population in order to
      minimize constipation as a medical problem.

PMID- 8160166
TI  - [Biofeedback treatment of fecal incontinence and constipation].
AB  - In summary, studies published in recent years on biofeedback training in
      defecation disorders--fecal incontinence and constipation--have presented
      convincing evidence that this method which derives from psychological learning
      theory has found clinical importance and relevance. Future research will need to
      demonstrate the mechanisms involved in its efficacy, the best clinical diagnosis
      and treatment modalities, and the long term effects of such management.

PMID- 8160167
TI  - [Intestinal pseudo-obstruction].
AB  - Intestinal pseudo-obstruction is a rare and heterogeneous syndrome caused by
      severe disorders of gastrointestinal motility. It affects the entire
      gastrointestinal tract or only segments, giving rise to symptoms and physical
      signs of a mechanical obstruction of the gut despite negative results of all
      imaging procedures. The disease may occur in an acute or chronic form. The acute
      and some of the chronic forms develop as complication of other gastrointestinal
      or extragastrointestinal diseases, e.g. pancreatitis or systemic sclerosis. The
      primary forms of chronic intestinal pseudo-obstruction are most often caused by
      genetic neuromuscular disorders of the gastrointestinal tract, e.g. familial
      visceral neuropathies. The diagnosis of intestinal pseudo-obstruction is based on
      the exclusion of a mechanical obstruction of the gut by fluoroscopy and
      endoscopy. Manometric studies may disclose the underlying disorder of
      gastrointestinal motility. In a few patients, results of all imaging procedures
      as well as motility studies are inconclusive, and laparatomy (with full thickness
      biopsy of the gut wall) has to be performed to exclude mechanical obstruction of
      the gut. Acute intestinal pseudo-obstruction is treated by elimination of the
      underlying intestinal or extraintestinal disease. In case of extensive colonic
      dilatation with imminent colonic perforation endoscopic decompression should be
      evaluated. Treatment of chronic pseudo-obstruction aims to correct the underlying
      motility disorder. Usually, restoration of normal gastrointestinal motility is
      attempted by prokinetic drugs, but often their effect is limited. Surgery may be
      helpful in the few patients in whom the disease is confined to small segments of
      the gut, leaving all other parts unaffected. Some patients with otherwise
      intractable disease may need long-term parenteral nutrition.

PMID- 8160168
TI  - [Lead and health].
AB  - As far as is known, lead is not required by animals. Lead poisoning is almost
      always caused by the oral ingestion of too much lead (alimentary contamination).
      Less than 44 mg lead per kilogram dry weight of feed is considered safe for
      cattle. Lead intoxication presents in a gastrointestinal form, an encephalic
      form, a haematological form, and as peripheral neuropathy. Zinc-protoporphyrin
      (ZPP) and zinc levels in blood should be measured to diagnose lead poisoning. The
      acceptable range of ZPP is 2.5 to 3.0 micrograms/g Hb(Fe) or less than 150
      micrograms/l; more than 250 micrograms/l is too high. Benelux regulations from
      1991 give acceptable concentrations for meat, kidneys, liver (between 0.3 and 0.1
      mg Pb per kilogram), and milk (0.05 mg Pb per kilogram) destined for human
      consumption. The treatment for lead poisoning is described.

PMID- 8160169
TI  - [A calf with a mesothelioma].
AB  - A 35-year-old Holstein-Friesian calf had shown progressive abdominal distension
      for two weeks. On admission, the calf showed signs of abdominal discomfort.
      Haemorrhagic fluid was obtained by paracentesis and contained 2.8 G.L-1.
      leucocytes. At both laparotomy and autopsy (after euthanasia) a mesothelioma was
      found.

PMID- 8160170
TI  - [Waste from veterinary practice: only the sun rises for nothing].

PMID- 8160171
TI  - [Swine's reaction to stress the same as in humans].

PMID- 8160172
TI  - [German shepherd puppy. Juvenile cellulitis].

PMID- 8160173
TI  - [Sudden fertility problems].

PMID- 8160174
TI  - [Drops in the neck].

PMID- 8160175
TI  - Relationship of urinary sodium and potassium and of urinary sodium/creatinine,
      potassium/creatinine and sodium/potassium ratios to stomach cancer and
      cerebrovascular disease mortalities in Japanese women.
AB  - To test Joossens's hypothesis that salt is a common cause of both cerebrovascular
      disease (CVD) and stomach cancer (SC), the standardized mortality ratios (SMRs)
      of SC and CVD were related to urinary Na and K and urinary Na/creatinine (Cr),
      K/Cr, and Na/K ratios. Fifty spot urine of females between 40 to 69 years was
      collected from each of 169 municipalities (88 urban and 81 rural) covering all
      prefectures in Japan using the filter paper sampling technique in 1985. While the
      SMR levels of CVD correlated significantly with Na, Na/Cr and Na/K, the SMR
      levels of SC showed no correlation with Na, K, Na/Cr, K/Cr or Na/K. It was
      therefore concluded that the geographical distribution of female SMR for SC could
      not be explained using only the urinary Na excretion as an index of Na intake,
      and that multiple risk factors and risk reducing factors should be taken into
      account to explain the distribution.

PMID- 8160176
TI  - Capsular properties of the shoulder.
AB  - The purpose of this study was to determine the structural properties of the
      capsule of the glenohumeral joint. Twelve fresh frozen cadaveric shoulders were
      studied. Capsular strips were prepared from four different sites (anterior,
      posterior, superior, and inferior) of the capsule. One end of the capsular
      sections was left attached to the humerus, and the other excised was fixed in a
      clamp of an Instron universal testing machine. Maximum load, strength (maximum
      stress), and modulus of elasticity of these four capsular portions were measured.
      The most common mode of failure was tear at the midsubstance (68%), followed by
      tear at the clamp-capsule junction (23%), and detachment from the humerus (9%).
      The posterior capsule (1.0 +/- 0.4 mm) was thinner than the anterior (1.8 +/- 0.3
      mm), superior (1.6 +/- 0.4 mm), and inferior capsule (1.5 +/- 0.3 mm). Among the
      four portions of the capsule, the posterior capsule showed the greatest strength
      (216.6 +/- 58.2 kg/cm2) and modulus of elasticity (683.1 +/- 228.8 kg/cm2),
      whereas the superior capsule showed the least strength (82.4 +/- 33.5 kg/cm2).
      There were no significant differences in maximum load. The greater strength of
      the posterior capsule may be one explanation for the low incidence of posterior
      shoulder dislocation.

PMID- 8160177
TI  - The generation of macrophages from precursor cells incubated with brain
      endothelial cells--a release of CSF-1 like factor from endothelial cells.
AB  - The perivascular macrophages in the brain are thought to be derived from bone
      marrow precursor cells. Results presented here demonstrate that immature
      macrophages obtained from nonadherent spleen cell populations can adhere to
      cerebrovascular endothelial cell (EC) monolayers and proliferate. The
      proliferation of these cells can be stimulated by either purified murine
      granulocyte-macrophage colony-stimulating factor (GM-CSF) or EC conditioned
      medium but not by IL-3. No proliferation of the GM-CSF- or IL-3-dependent murine
      cell line IC-2 was observed in the presence of EC conditioned medium. Macrophage
      like cells could also be derived from murine bone marrow cells but inhibited by
      anti-macrophage-CSF (M-CSF or CSF-1). The capacity of EC conditioned medium to
      induce the proliferation of macrophage-like cells from the spleen is therefore
      not due to the release of GM-CSF but CSF-1. In concomitant experiments using
      mature macrophages incubated on EC monolayers, no proliferation was observed.
      These findings suggest that the growth of perivascular macrophages in the brain
      may be stimulated by cerebrovascular EC.

PMID- 8160178
TI  - Increasing trends in mortality rate of aortic aneurysms in Japan, 1955-90.
AB  - To know the characteristics of mortality from aortic aneurysms in Japan, the age
      adjusted and age-specific mortality rates of the diseases were calculated based
      on the Vital Statistics of Japan published from the Statistics and Information
      Department, Minister's Secretariat, Ministry of Health and Welfare. The overall
      age-adjusted mortality rate increased 24.8-fold from 0.43 to 10.98 per 100,000
      for males, and 18.6-fold from 0.23 to 4.54 per 100,000 for females from 1955-90.
      The most common type was abdominal aortic aneurysms followed by dissecting and
      thoracic aortic aneurysms. The mortality rates of dissecting and thoracic aortic
      aneurysms increased greater than that of abdominal aortic aneurysms. The
      mortality rate of dissecting aneurysms was higher than that of abdominal and
      thoracic aortic aneurysms in age groups of 64 years or under. The mortality rate
      of abdominal aortic aneurysms was the most common in age groups of 65 years or
      over.

PMID- 8160179
TI  - A huge non-invasive thymoma causing acute dyspnea.
AB  - We report a patient with an extra-ordinarily huge thymoma weighing 1,930 g and
      measuring 21 x 20 x 15 cm that filled almost the entire hemithorax. The tumor was
      successfully removed and the patient made a good recovery. Despite of its large
      size, the tumor was benign both clinically and histologically, and the
      pathological diagnosis was epithelial thymoma of non-invasive type. The
      perioperative changes of this patient's lung function are discussed in detail.

PMID- 8160180
TI  - Results of surgical treatment for calcified tuberculous empyema: improved
      pulmonary function obtained with lung preserving policy.
AB  - We treated thirteen cases of calcified tuberculous empyema during the nine years
      from 1984 to 1992. Six patients having mild symptoms were categorized as Type I,
      and the remaining seven with severe symptoms as Type II. The patients of Type I
      were all successfully treated by complete empyemectomy with or without lung
      resection. All the patients of Type II suffered from major symptoms and were
      burdened by larger empyema cavities with formation of bronchial fistulas. Five of
      the latter were successfully treated, but two died, one from MRSA infection and
      another from intestinal necrosis following omentopexy. Our guide lines for the
      treatment of tuberculous empyema are: Lung resection must be minimal. Type I
      patients could be managed by simple empyemectomy with or without minor
      thoracoplasty. Open thoracostomy prior to the empyemectomy is not necessary. If
      the patient who belongs to Type II is aged and in a critical state, open
      thoracostomy must be taken as the first choice. Omentopexy is reliable, but it
      should be restricted to selected cases. Reasonable dead space and minor air
      leakage may safely be left behind if the cavity is surrounded by noninfected raw
      surface of the chest wall and diaphragm. Better quality of life was revealed by
      exercise test with improved oxygen consumption, compared to the preoperative
      state.

PMID- 8160181
TI  - Comparative studies on proteodermatan sulfate of bovine gastrointestinal tract.
AB  - Proteodermatan sulfate was extracted from four areas of the bovine
      gastrointestinal tract (esophagus, stomach, small intestine and colon) with 4 M
      guanidine-HCl and then purified by ion-exchange and gel filtration
      chromatography. Dermatan sulfate chains which made up proteodermatan sulfate from
      each area were separately prepared by Pronase P and endo-beta-xylosidase
      digestion. The properties of the proteodermatan sulfate and dermatan sulfate
      chains were compared using electrophoresis and high-performance liquid
      chromatography. The molecular size of proteodermatan sulfate purified from each
      area was estimated to be greater than 8 x 10(5), and the molecular sizes of
      dermatan sulfate chains from esophagus, stomach, small intestine, and colon were
      27,000, 24,500, 21,000, and 21,500, respectively. The dermatan sulfate chains
      from the esophagus were slightly undersulfated in comparison with the others.
      These results show that the molecular sizes of proteodermatan sulfate from
      different regions of the gastrointestinal tract are similar to each other, but
      are larger than those from other tissues. Dermatan sulfate chains differed from
      each other to a slight degree with respect to chain length and sulfation, that
      from the esophagus being the largest. These differences in proteodermatan sulfate
      structure seem to reflect the organ specificities of the gastrointestinal tract.

PMID- 8160182
TI  - Special issue: Pore-forming toxins and antimicrobial polypeptides.

PMID- 8160183
TI  - Pardaxin: channel formation by a shark repellant peptide from fish.
AB  - The results of the various studies describing the mechanism involved in pore
      formation by pardaxin and some of its analogues, support a 'barrel-stave' model
      (Ehrenstein amd Lecar, 1977). In this model pardaxin exerts its activity via
      three successive steps: (i) a fast binding step (as reflected by the rapid
      increase of NBD fluorescence in the presence of vesicles); (ii) insertion of
      peptides into the lipid bilayer; and (iii) the monomers aggregate into a barrel
      like formation in which a central aqueous pore surrounded by proteins is formed.
      This pore increases in diameter through the progressive recruitment of additional
      monomers. Both the fluorescence energy transfer (FET) studies and the observation
      of a significant difference in the increase of NBD fluorescence, depending on
      which terminal was labelled by the fluorophore, support a model by which
      aggregates are formed in an ordered parallel manner, where the C-terminus is more
      exposed to the aqueous phase.

PMID- 8160184
TI  - Iturins, a special class of pore-forming lipopeptides: biological and
      physicochemical properties.
AB  - Iturins are a family of lipopeptides extracted from the culture media of various
      strains of Bacillus subtilis. These amphiphilic compounds are characterized by a
      peptide ring of seven amino acid residues including an invariable D-Tyr2, with
      the constant chiral sequence LDDLLDL closed by a C14-C17 aliphatic beta-amino
      acid. They exhibit strong antifungal activities against a wide variety of
      pathogenic yeasts and fungi but their antibacterial activities are restricted to
      some bacteria such as Micrococcus luteus. The biological activity of the iturin
      lipopeptides is modulated by the primary structure of the peptide cycle as
      illustrated by the methylation of the D-Tyr2 residue which dramatically decreases
      the activity or by the inversion of the two adjacent Ser6-Asn7 residues which
      makes mycosubtilin more active than iturin A. The antifungal activity is related
      to the interaction of the iturin lipopeptides with the cytoplasmic membrane of
      target cells, the K+ permeability of which is greatly increased. The ability of
      iturin compounds to increase the membrane cell permeability is due to the
      formation of ion-conducting pores, the characteristics of which depend both on
      the lipid composition of the membrane and on the structure of the peptide cycle.
      From monolayer experiments it has been suggested that these ionic pores are the
      consequence of the presence of aggregates (lipopeptide aggregates or
      lipopeptide/phospholipid complex aggregates) in the phospholipid membrane. It has
      also been shown that, when active, iturins interact strongly with sterols,
      forming lipopeptide/cholesterol complexes. Therefore, the biologically efficient
      structure might be a ternary structure: iturin/phospholipid/sterol.

PMID- 8160185
TI  - Structure and membrane actions of a marine worm protein cytolysin, Cerebratulus
      toxin A-III.
AB  - Four homologous Cerebratulus lacteus A toxins are the first and as yet only
      protein cytolysins to be isolated from an ancient phylum of marine worms, the
      nemertines. The most abundant and toxic variant, toxin A-III, has been sequenced
      and its mechanisms of action studied in the most detail. It consists of a single
      basic polypeptide chain of 95 amino acid residues cross-linked by three disulfide
      bonds, and possesses a predominantly alpha-helical secondary structure. The C
      terminal third of the toxin sequence is postulated to be a helical 'hairpin'
      structure involved in pore formation. Toxin A-III permeabilizes a variety of
      cells as well as liposomes made from a variety of phospholipids; apparently large
      pores are formed, as large proteins are released almost as rapidly as small
      organic molecules and inorganic ions. At sublytic concentrations, the toxin also
      inhibits protein kinase C and endogenous voltage-gated cation selective (sodium,
      calcium) channels occurring in the nervous and cardiovascular systems. A curious
      observation, also reported for colicins and some other protein cytolysins, was
      the conservation of toxin secondary structure upon insertion into phospholipid
      liposomes, despite the strong likelihood that significant changes in tertiary
      structure occur to provide a hydrophobic surface for interaction with membrane
      lipids. Because of its small size and presumed single helical hairpin secondary
      structure, Cl toxin A-III is an excellent molecular subject for investigating
      protein insertion into biological membranes and mechanisms of pore formation.

PMID- 8160186
TI  - The membrane attack complex of complement. Assembly, structure and cytotoxic
      activity.
AB  - The membrane attack complex of complement is formed by the molecular fusion of
      the five terminal complement proteins, C5, C6, C7, C8, and C9. While the assembly
      process on a target membrane and its modulation by restriction factors present on
      host cells is now quite well understood the molecular details of the architecture
      of the complex still need much further clarification. This is especially true for
      the interaction of the last acting protein C9, which provides the cytotoxic
      action of the complex, with the precursor C5b-8 complex. Because of this lack of
      structural details the molecular mechanisms that lead to complement-mediated cell
      death remain cryptic, however, it is hoped that recent advances in controlling
      the assembly process and in site-specific modification of the terminal complement
      proteins by recombinant DNA techniques should change this predicament quickly.

PMID- 8160187
TI  - Pore-formation by Escherichia coli hemolysin (HlyA) and other members of the RTX
      toxins family.
AB  - Escherichia coli hemolysin (HlyA) is a major cause of E. coli virulence. It lyses
      erythrocytes by a colloid osmotic shock due to the formation of hydrophilic pores
      in the cell wall. The size of these channels can be estimated using osmotic
      protectant of increasing dimensions. To show that the formation of pores does not
      depend critically on the osmotic swelling we prepared resealed human erythrocyte
      ghosts loaded with a fluorescent marker. When attacked by HlyA the internal
      marker was released, indicating the formation of toxin channels so large as to
      let it through. The channels can be directly demonstrated also in purely lipidic
      model systems such as planar membranes and unilamellar vesicles, which lack any
      putative protein receptor. HlyA has been recognised as a member of a large family
      of exotoxins elaborated by Gram-negative organisms including Proteus, Bordetella,
      Morganella, Pasteurella and Actinobacillus. These toxins have quite different
      target cell specificity and in many cases are leukocidal. When tried on planar
      membranes however, even specific leukotoxins open channels not dissimilar from
      those formed by HlyA, suggesting this might be a common step in their action.
      Comparison of the hydrophobic properties of six members of the toxin family
      indicates the presence of a conserved cluster of ten contiguous amphipathic
      helixes, located in the N-terminal half of the molecule, which might be involved
      in channel formation.

PMID- 8160188
TI  - Clostridium perfringens enterotoxin acts by producing small molecule permeability
      alterations in plasma membranes.
AB  - Clostridium perfringens enterotoxin (CPE) appears to utilize a unique mechanism
      of action to directly affect the plasma membrane permeability of mammalian cells.
      CPE action involves a multi-step action which culminates in cytotoxicity.
      Initially CPE binds to a protein receptor on mammalian plasma membranes. The
      membrane-bound CPE then becomes progressively more resistant to release by
      proteases (a phenomenon consistent with the insertion of CPE into membranes).
      This 'inserted' CPE then participates in the formation of a large complex in
      plasma membranes which contains one CPE: one 70 kDa membrane protein: one 50 kDa
      membrane protein. Upon formation of large complex, plasma membranes become freely
      permeable to small molecules such as ions and amino acids. This CPE-induced
      disruption of the cellular colloid-osmotic equilibrium then causes secondary
      cellular effects and cell death.

PMID- 8160189
TI  - Pore-forming Pseudomonas aeruginosa cytotoxin.
AB  - Pseudomonas aeruginosa procytotoxin protein is processed C-terminally during
      bacterial autolysis to generate the active 29-kDa cytotoxin molecule. Binding to
      target cell membranes is dependent upon Cys23 and Cys215 and a domain flanked to
      Cys215. On rabbit erythrocytes, cytotoxin binds to a 28-kDa peptide of a
      glycoprotein, its N-terminus shows high homology to channel integral membrane
      protein CHIP28. At concentrations of more than 3 x 10(-9) M, cytotoxin increases
      plasma membrane permeability of most eucaryotic cells investigated. The role of
      cytotoxin in the formation of pores with a diameter of 2 nm on mammalian cells is
      discussed. The cytotoxin effects are coordinated with other pseudomonal products
      and the resultant concept of pathogenesis is presented.

PMID- 8160190
TI  - All in the family: the toxic activity of pore-forming colicins.
AB  - Colicins are unusual bacterial toxins because they are directed against close
      relatives of the producing strain. They kill their targets in one of three
      distinct ways; via a ribonuclease or deoxyribonuclease activity or by forming
      pores in the target cell's membrane. This review deals with the steps involved in
      pore-forming colicin activity including, initial synthesis of the toxin, toxin
      release, receptor binding, translocation across the periplasm and pore formation
      in the cytoplasmic membrane. Special reference is made to the role of colicin in
      vivo, the structural changes occurring during pore formation and the role of the
      immunity protein.

PMID- 8160191
TI  - A review of axonal transport of metals.
AB  - Neurons have efficient mechanisms for the transport of organelles and chemical
      substances in axons to the nerve terminals and back to the cell bodies. Enzymes
      involved in transmitter synthesis, peptide transmitters and their precursors are
      examples of macromolecules that are transported down the axon, anterogradely. For
      final degradation and possible reuse, many constituents are transported back to
      the cell body, retrogradely. Retrograde transport is also a pathway by which
      certain toxins may bypass the blood-brain barrier and accumulate in neurons. In
      recent years, it has been shown that certain metals may accumulate in neurons
      following retrograde transport. The metals for which retrograde transport has
      been demonstrated include lead, cadmium and mercury. In this article recent
      findings regarding axonal transport of metals are reviewed. The putative
      mechanisms involved in the uptake of metals into the nerve terminal and the fate
      of metals in the cell body are outlined. Axonal transport of metals as a possible
      etiological factor in diseases of the human nervous system is discussed.

PMID- 8160192
TI  - Induction of poly(ADP-ribosyl)ation in the kidney after in vivo application of
      renal carcinogens.
AB  - Dichlorovinylcysteine, the key metabolite thought to be responsible for the
      nephrocarcinogenicity of trichloroethene and dichloroacetylene, induces DNA
      double-strand breaks followed by increased poly(ADP-ribosyl)ation of nuclear
      proteins in cultured renal cells (Vamvakas et al., 1992, Biochem. Pharmacol. 44,
      1131-1138). Poly(ADP-ribosyl)ation represents a post-translational modification
      of nuclear proteins involved in DNA repair, DNA replication, and modulation of
      gene expression. The present study investigates the induction of DNA double
      strand breaks and poly(ADP-ribosyl)ation in the renal cortex after in vivo
      administration of several renal carcinogens to male Wistar rats, and the temporal
      relationship between these two processes. Dichlorovinylcysteine caused a time
      dependent increase in the amount of poly(ADP-ribosyl)conjugates in the kidney
      cortex, which was preceded by increased formation of DNA double-strand breaks.
      Potassium bromate and ferric nitrilotriacetate, whose nephrocarcinogenicity is
      thought to result from increased formation of reactive oxygen species, both
      induced poly(ADP-ribosyl)ation with the concomitant formation of DNA double
      strand breaks. Dimethylnitrosamine, an indirect acting methylating agent, and
      trimethylpentane, a non-genotoxic renal carcinogen, failed to induce poly(ADP
      ribosyl)ation or a significant increase in DNA double-strand breaks in the renal
      cortex. The results indicate that nephrocarcinogens capable of inducing DNA
      fragmentation also induce post-translational modification of renal proteins via
      increased poly(ADP-ribosyl)ation.

PMID- 8160193
TI  - Comparison of in vivo and in vitro rat hepatic toxicity of coumarin and methyl
      analogues, and application of quantitative morphometry to toxicity in vivo.
AB  - The rat hepatic toxicity of coumarin and methyl analogues (3-,4-methyl coumarin
      and 3,4-dimethylcoumarin) has been determined in vivo and in vitro (freshly
      isolated cells). Coumarin at a dose of approximately 1 mmol/kg produced clear
      histological evidence of centrilobular necrosis, while the methyl analogues at an
      equivalent dose were much less toxic. By use of a systematic random sampling
      protocol and quantitative morphometry it was determined that there was a lobar
      variation in the extent of hepatic damage but that this exhibited random inter
      animal variation. The order of cytotoxicity in vitro was identical to that
      observed in vivo. In hepatocytes depleted of glutathione the toxicity of all four
      compounds was increased. This was particularly marked for the 3-methyl analogues,
      such that the order of toxicity was different to that observed in vivo and in
      hepatocytes not depleted of glutathione.

PMID- 8160194
TI  - Cadmium induces apoptosis in a human T cell line.
AB  - Cadmium, a potent toxic metal, poses a serious environmental threat but the
      mechanisms of its toxicity remain unclear. In the present study, we investigated
      the nature of cadmium-induced cell death in the human T cell line CEM-C12.
      Cadmium was time- and dose-dependently toxic for CEM-C12 cells, cell death being
      preceded by chromatin condensation and DNA fragmentation. Quantification of the
      latter indicated an increase above 4 microM cadmium, with maximal fragmentation
      at 8 to 10 microM. By contrast, when CEM-C12 cells were exposed to higher cadmium
      concentrations (50 microM), cell death increased without concomitant chromatin
      condensation or DNA fragmentation. Thus, cadmium at low and high concentration
      kills CEM-C12 cells by apoptosis and necrosis, respectively. Addition of
      cycloheximide reduced the apoptotic effect of cadmium, suggesting that cadmium
      induced apoptosis is an process depending on protein synthesis. Verapamil, a
      calcium/potassium channel blocker, markedly increased the viability of CEM-C12
      cells treated by low cadmium concentrations and prevented DNA fragmentation. The
      apoptotic effect of cadmium suggests a possible mechanism for lymphocyte damage
      occurring after in vivo exposure to cadmium.

PMID- 8160195
TI  - Resistance of rat kidney mitochondrial membranes to oxidation induced by acute
      iron overload.
AB  - The effect of iron-overload on rat kidney was studied after a single injection of
      iron-dextran. Total iron content in kidney and isolated kidney mitochondria was
      markedly elevated over control values. To assess mitochondrial damage by iron
      overload, succinate-cytochrome c reductase and NADH-cytochrome c reductase
      activities as well as the rate of succinate-dependent hydrogen peroxide
      generation were measured. None of these activities were significantly affected by
      acute iron overload. The net content and the rate of TBARS (thiobarbituric acid
      reactive species) formation in kidney homogenates from iron-treated rats was
      significantly higher than that of control animals. Total superoxide dismutase
      activity in the homogenates from iron overloaded kidney was decreased by 26%, as
      compared to controls. Catalase, glutathione peroxidase, and Mn-superoxide
      dismutase activities were not affected by the treatment. The content of alpha
      tocopherol was consistently decreased in whole kidney homogenates (-31%),
      mitochondria from kidney medulla (-31%) and cortex (-34%), from iron-overloaded
      rats. Our data suggest that iron dextran treatment does not affect kidney
      integrity, even though increases in lipid peroxidation occur. Vitamin E appears
      to be effective in controlling iron-dextran dependent radical generation in
      kidney.

PMID- 8160196
TI  - Induction of respiratory hypersensitivity to diphenylmethane-4,4'-diisocyanate
      (MDI) in guinea pigs. Influence of route of exposure.
AB  - The induction of respiratory sensitization in guinea pigs to diphenylmethane-4,4'
      diisocyanate (MDI), a known human respiratory allergen, has been investigated and
      different routes of exposure compared. Guinea pigs were exposed to MDI by i.d.
      injection, by topical application or by inhalation. Pulmonary hypersensitivity
      was measured subsequently as a function of changes in respiratory rate following
      challenge with atmospheres containing MDI. In addition, contact hypersensitivity
      was measured by topical challenge and antibody responses evaluated by enzyme
      linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA).
      Attempts to sensitize guinea pigs by inhalation exposure to MDI were
      unsuccessful. Antibody responses and contact sensitization were both infrequent
      and low grade, and no animals exhibited pulmonary responses following challenge
      with atmospheric MDI. In contrast, sensitization by either i.d. injection or
      topical application of MDI induced antibody responses in the majority of animals.
      Moreover, a proportion of animals in each case exhibited pulmonary responses
      following subsequent inhalation challenge. These data indicate that the route of
      exposure influences markedly the effectiveness of sensitization to respiratory
      allergens such as MDI and that skin contact may be an important cause of
      occupational respiratory allergy.

PMID- 8160197
TI  - Acute N-(3,5-dichlorophenyl)succinimide nephrotoxicity in female Fischer 344
      rats.
AB  - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an
      established nephrotoxicant in male Fischer 344 rats at i.p. doses of > or =
      mmol/kg. Since gender differences often exist in the susceptibility to toxicants,
      the nephrotoxic potential of NDPS was examined in female Fischer 344 rats. Rats
      (4-5/group) were administered NDPS (0.1, 0.2, 0.4, or 1.0 mmol/kg, i.p.) or
      vehicle (sesame oil, 2.5 ml/kg) and renal function monitored for 48 h. At a dose
      of 0.1 mmol/kg, NDPS had no effect on renal function. However, administration of
      NDPS at a dose of 0.2 or 0.4 mmol/kg resulted in marked nephrotoxicity
      characterized by diuresis, increased proteinuria, glucosuria, hematuria, elevated
      blood urea nitrogen (BUN) concentration and kidney weight, decreased organic ion
      accumulation and proximal tubular necrosis. NDPS treatment of 1.0 mmol/kg
      resulted in oliguric renal failure rather than polyuric renal failure in 3 of 4
      rats. Proximal tubular damage was observed primarily in the S3 segment of the
      proximal tubule in NDPS-treated female rats, while in male rats the S1 and S2
      segments are the initial renal targets. These results demonstrate that female
      Fischer 344 rats are more susceptible to NDPS nephrotoxicity than male Fischer
      344 rats and that the site of the renal lesion is gender dependent.

PMID- 8160198
TI  - An impurity present in some samples of SIN-1 oxidizes it to nitric oxide in
      anaerobic solutions.
AB  - N-Morpholino-N-nitrosoaminoacetonitrile (SIN-1), a nitrovasodilator metabolite of
      the drug, molsidomine, is widely used in studies on the pharmacology and
      toxicology of nitric oxide (NO) because solutions of SIN-1 'spontaneously'
      release NO in a pathway involving molecular oxygen. Preliminary results, however,
      suggested that SIN-1 could react with hemoglobin in anaerobic solutions to
      release NO and form NO-hemoglobin. Electron paramagnetic resonance (EPR) studies
      showed that heme(III) of methemoglobin was not being reduced, thereby not serving
      as the oxidant in the reaction generating NO-hemoglobin. When anaerobic solutions
      of SIN-1 and hemoglobin kept in the light and in the dark were compared,
      substantially more NO-hemoglobin was eventually generated in the dark, indicating
      that SIN-1 did not undergo photochemical decomposition to NO under the conditions
      used. Solutions of NO-hemoglobin were equally stable under these same conditions
      of light and dark. The initial pH (7.0) of stirred, unbuffered solutions of SIN-1
      decreased at nearly the same rate whether or not oxygen was present. Anaerobic
      and aerobic solutions plateaued at the same pH, namely 5.4. Anaerobic solutions
      of SIN-1 in phosphate buffer, pH 7.4, released NO to the gas phase, where it was
      identified by trapping it with hemoglobin on agarose beads and deriving the
      characteristic NO-hemoglobin EPR spectrum. High pressure liquid chromatography
      revealed the presence of an unknown species with a retention time between that of
      SIN-1 and molsidomine. Samples from two different lots of SIN-1 contained this
      impurity which appears to oxidize SIN-1 to products that release NO in the
      absence of oxygen. This unknown impurity may be unstable toward light.

PMID- 8160199
TI  - Exogenous glutathione attenuates the antiproliferative effect of buthionine
      sulfoximine.
AB  - Buthionine sulfoximine (BSO) inhibits proliferation of human lung carcinoma A549
      cells in a manner that does not correlate with intracellular glutathione (GSH)
      depletion, nor does it reflect overt toxic effects of BSO. However, BSO inhibits
      uptake by A549 cells of cystine, which is an essential amino acid for cell growth
      in culture. Thus, it is hypothesized that inhibition of cellular cystine uptake
      is, or is partially, responsible for the antiproliferative effect of BSO. It has
      been shown that the gamma-glutamyl amino acid transport system plays a role in
      cystine transport across cell membranes. This transport system requires
      extracellular GSH for its operation. BSO, by inhibiting intracellular GSH
      synthesis, would reduce GSH export and decrease extracellular GSH levels.
      Therefore, the present study was undertaken to examine the effect of exogenously
      added GSH on BSO inhibition of cellular cystine uptake and its relationship to
      the antagonistic effect of GSH on BSO antiproliferation. A549 cells were treated
      with 10 mM BSO and exogenous GSH was added to these BSO-treated cultures. Effects
      of exogenous GSH on BSO antiproliferation and cellular GSH depletion were
      determined simultaneously as a function of time. The effect of GSH on BSO
      inhibition of cystine accumulation was measured using [35S]cystine. The results
      obtained demonstrate that exogenously added GSH partially overcame BSO
      antiproliferation. The GSH antagonistic effect did not correlate with repletion
      of intracellular GSH, but it did correlate with recovery of BSO-inhibited cystine
      accumulation. Exogenous GSH also enhanced proliferation of non-BSO treated cells
      at concentrations below 1.0 mM. The results of this study suggest that BSO
      inhibition of cystine uptake may represent one mechanism by which BSO exerts its
      antiproliferative effect. The antagonistic effect of exogenous GSH on BSO
      antiproliferation may result from recovery of BSO-inhibited cystine uptake,
      although other mechanisms responsible for the GSH antagonistic effect may also
      exist.

PMID- 8160200
TI  - Inter-individual variability of human hepatic glutathione S-transferase isozymes
      assessed by inhibitory capacity.
AB  - Glutathione S-transferases (GSTs) are important as drug metabolizing enzymes
      mainly in the detoxication process. To assess individual differences in
      susceptibility to different chemicals, it would be useful to know the activity of
      specific GST isozymes in individuals. In order to study individual variability,
      typical substrates specific for the three major classes of GSTs were used not
      only as substrates but also as inhibitors using 17 organ-donor livers. Out of 17,
      4 livers were low in the mu-form isozyme, judging from the depressed GST activity
      for trans-4-phenyl-3-buten-2-one (tPBO), a mu-class substrate. The range of tPBO
      activity exhibited more than 20-fold variation, while less than 2-fold variation
      was observed in the activities for 1-chloro-2,4-dinitrobenzene (CDNB), a non
      specific substrate for alpha-, mu-, and pi-class GSTs. In addition to the
      conventional approach to assessing individual variability, well known substrates
      for GSTs, cumene hydroperoxide (CHP, alpha-class), tPBO (mu) and ethacrynic acid
      (EA, pi) were used as inhibitors against CDNB-GSH conjugation. CHP inhibited the
      CDNB-GSH conjugation in mu-depressed livers more potently than in the non
      depressed livers, probably because CHP is a specific inhibitor for alpha-class
      GST. Inhibition by CHP may therefore be used to detect livers which are low in mu
      form. The inhibition by tPBO was found to be weak and the variability was small
      (CV of 9% in 17 livers). EA potently inhibited GST activity with its inhibition
      constant (Ki) 2,000-fold lower than that of CHP. The small individual variation
      in inhibition by EA (CV of 6%) supported that EA is a universal but potent
      inhibitor against major GSTs contained in human liver.

PMID- 8160201
TI  - Induction of serum borne immunomodulatory factors in B6C3F1 mice by carbon
      tetrachloride. Exposure to carbon tetrachloride produces an increase in B-cell
      number and function.
AB  - Carbon tetrachloride exposure in mice induces a serum associated
      immunosuppressive factor(s) that inhibits T-cell dependent immune responses. The
      objective of the present studies was to characterize the immunomodulatory
      activity of serum isolated from carbon tetrachloride-treated mice on T-cell
      independent humoral immune responses. Direct addition of serum isolated from
      carbon tetrachloride-treated mice (500 mg/kg/day for 7 days) to naive spleen cell
      cultures enhanced the antibody forming cell response to lipopolysaccharide as
      compared to serum from naive or vehicle-treated mice. Enhanced antibody forming
      cell responses were also observed when spleen cells isolated from carbon
      tetrachloride-treated mice were sensitized with this T-cell independent antigen
      24 h, but not 48 h or 72 h, following exposure of mice to one dose of 500 or 1000
      mg/kg of carbon tetrachloride. Additionally, spleen weight and spleen:body weight
      ratio were increased in mice sensitized in vivo with sheep red blood cells 24 h
      after exposure to a single dose of carbon tetrachloride (500 or 1000 mg/kg) as
      compared to naive antigen sensitized mice and mice sensitized 48 and 72 h after
      exposure to carbon tetrachloride. Fluorescence activated cell sorting analysis
      indicated that daily exposure to carbon tetrachloride (250 or 500 mg/kg for 7
      days) increased the percentage of B-cells in the spleen without altering the
      number of TH-cell or TC/S cell populations. Taken together, these results suggest
      that exposure to carbon tetrachloride induces a serum borne factor(s) that
      produces a modest increase in the functional activity and number of B-cells in
      the spleen.

PMID- 8160202
TI  - Evaluation of the effect of low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin
      exposure on cell mediated immunity.
AB  - The immunotoxicity of TCDD in the mouse has been well documented. To date, the
      most sensitive endpoint to TCDD-induced toxicity in mice is that reported by
      Clark et al. (Clark, D. A., Gauldie, J., Szewczuk M. R. and Sweeney, G. (1981)
      Proc. Soc. Exper. Biol. Med. 168, 290.) who found that TCDD suppressed the murine
      cytotoxic T lymphocyte (CTL) response following four weekly doses of 4 ng
      TCDD/kg/week. However, these results have never been corroborated, as other
      laboratories have been unable to detect immunosuppression by TCDD at such low
      levels. In this study, we evaluated the effect of TCDD on the in vivo- and in
      vitro-generated CTL response to P815 mastocytoma cells in adult C57BL/6J female
      mice via a 51Cr release assay. Mice were given weekly intraperitoneal injections
      of TCDD or vehicle for 4 weeks at dosages ranging from 0.01 to 3.00
      micrograms/kg/week. No statistically significant suppression of the in vivo- or
      in vitro-generated CTL response was detected at any dosage. As expected,
      significant increases in liver weights and decreases in thymus weights were
      observed at TCDD dosages of 1.0 and 3.0 micrograms/kg/week. Likewise, suppression
      of the antibody plaque-forming cell response to sheep erythrocytes was observed
      at dosages of 1.0 and 3.0 micrograms TCDD/kg/week. Although expected humoral
      immunosuppression and organ effects were observed, our data do not support
      suppression of murine CTL responses at the TCDD doses employed in this study.

PMID- 8160203
TI  - Cytokine-mast cell interactions: relevance to IgE-mediated chemical allergy.
AB  - Recent work has shown that certain cytokines (inducible secreted proteins) are
      potent regulators of mast cell development and secretory function. We know also
      that sensitization of mice to chemical allergens induces T cell-dependent immune
      responses in which cytokines play an important role. Combining these
      observations, we postulate that in vivo T cell responses might influence, via the
      production of cytokines, the behaviour of mast cells in situ. In support of this
      hypothesis we have found that mast cells isolated from chemical allergen
      sensitized mice show enhanced responsiveness to IgE-dependent activation in
      vitro. This effect is seen with chemical allergens that are either contact or
      respiratory sensitizers in man. Although respiratory and contact allergens cannot
      be distinguished according to their ability to modulate mouse mast cell function
      in vivo, they can be separated on the basis of their differential ability to
      induce specific IgE-dependent mast cell sensitization. In conclusion, the mouse
      may offer a useful model for investigating and predicting the potential of
      chemicals to act as mast cell promoting agents and/or respiratory sensitizers.

PMID- 8160204
TI  - Dose-response relationship for rat liver DNA damage caused by 49 rodent
      carcinogens.
AB  - An experimental approach was taken to the question of dose-response curves for
      chemical carcinogenesis. DNA damage in female rat liver was chosen as the
      experimental parameter because all chemicals found to damage hepatic DNA were
      rodent carcinogens. The lowest dose causing DNA damage was determined for the 12
      active chemicals (1,2-dibromoethane, 1,2-dibromo-3-chloropropane, 1,2
      dichloroethane, 1,4-dioxane, methylene chloride, auramine O, Michler's ketone,
      selenium sulfide, 1,3-dichloropropene, 1,2-dimethylhydrazine, N-nitroso
      piperidine and butylated hydroxytoluene). The resulting dose-response curves for
      rat hepatic DNA damage were plotted versus log of the molar dose (all activity
      was in five orders of magnitude) and versus percent of chemicals' oral rat LD50
      (most of the activity was in only two orders of magnitude). Dose-response studies
      of the active chemicals were analyzed by regression methods. With the exception
      of butylated hydroxytoluene, the dose-response curves fit a linear model well (r2
      = 0.886) and a quadratic model even better (r2 = 0.947). Based on experimental
      data from 11 DNA-damaging carcinogens (a dose range of 6 orders of magnitude), an
      equation and graph of the dose-response relationship of an 'average DNA-damaging
      carcinogen' is presented over the x-axis dose range of eight orders of magnitude.

PMID- 8160206
TI  - Transforming growth factor beta-induced tolerance to cadmium cytotoxicity in
      cultured vascular endothelial cells.
AB  - We investigated whether or not transforming growth factor beta (TGF beta 1)
      affects the sensitivity to cadmium of bovine aortic endothelial cell in a culture
      system. Cadmium cytotoxicity was evaluated by [3H]adenine release assay. It was
      found that pretreatment with recombinant human TGF beta 1 (rhTGF beta 1) of the
      confluent cultures resulted in a reduction of cadmium cytotoxicity, suggesting
      that the cytokine induced a tolerance to cadmium in the cells. Such a tolerance
      was induced slightly by either recombinant human tumor necrosis factor alpha or
      recombinant human basic fibroblast growth factor but not by recombinant human
      interleukin-1 beta and -6; rhTGF beta 1 was the most potent inducer. rhTGF beta 1
      failed to induce the tolerance in the presence of anti-rhTGF beta 1 antibody.
      Pretreatment with the antibody alone caused a significantly sensitive response to
      cadmium, suggesting that endogenous TGF beta 1 can physiologically contribute to
      protection against cadmium cytotoxicity in endothelial cells. The accumulation of
      cadmium was increased in the extracellular fraction but significantly decreased
      in the intracellular fraction of the cells by pretreatment with rhTGF beta 1. The
      cadmium content was significantly decreased in the particulate fraction but not
      in the cytosol fraction. Gel filtration chromatography of the cytosol fraction
      revealed that cadmium was bound to high-molecular-weight protein and
      metallothionein; both peaks were slightly increased by pretreatment with rhTGF
      beta 1. It was concluded that rhTGF beta 1 induces a tolerance to cadmium in
      cultured endothelial cells, caused by a decrease in the cadmium accumulation in
      the particulate fraction of the cells. TGF beta 1 may serve as a protective
      factor against cadmium cytotoxicity in vascular endothelial cells.

PMID- 8160205
TI  - In vitro exposure of tracheobronchial epithelial cells and of tracheal explants
      to ozone.
AB  - An in vitro system for exposing respiratory epithelial cells or explant tissues
      to ozone has been developed and characterized. This system is designed to
      generate and monitor consistent, reproducible levels of ozone, over a range of
      concentrations, in a humidified atmosphere, and to allow an exposure time of 24 h
      or longer. Based on chemical analysis, highly reproducible concentrations of
      ozone are delivered throughout the chamber, with a coefficient of variation of <
      5% between five replicate vials exposed to 0.5 ppm of ozone for 50 min. The
      viability of cultured human tracheobronchial epithelial cells, as measured by the
      ability to oxidize a vital dye, and of rat tracheal epithelium, as measured by
      total numbers of necrotic cells in tracheal explants, after ozone exposure was
      examined in this system. Responses of cultured cells to ozone exposure as
      measured by bioassay were consistent with the observed low level of variability
      of ozone concentration between replicate incubation dishes or vials. Responses of
      cultured cells to ozone were proportional to duration of exposure and inversely
      proportional to the volume of medium covering the cells. We conclude that this
      newly developed in vitro exposure system will allow relatively simple and
      convenient exposure of cultured cells or organs to ozone or other gaseous agents
      under highly controlled and reproducible conditions.

PMID- 8160207
TI  - Sensory irritation, pulmonary irritation and structure-activity relationships of
      alcohols.
AB  - Sensory irritation due to inhalation of n-pentanol, n-heptanol, sec-butanol and
      tert-pentanol was determined from the reflexively induced decrease in respiratory
      rate in CF-1 mice. The concentration-effect relations followed Michaelis-Menten
      equations, complying with receptor mediated processes. The relations were
      transformed into nearly rectilinear relationships in log concentration-effect
      plots, and the extrapolated threshold concentrations (RD-0) from the lines were
      120, 28, 640 and 1210 ppm, respectively, obtained from the first 2 min of the
      exposure period. These values were comparable to those found in Swiss-Webster
      mice and to those obtained by electrophysiological experiments in Sprague-Dawley
      rats. The hydrophobic properties of the receptor biophase were found to approach
      that of the internal part of the bilayer membrane. Estimates on threshold limit
      values (TLV) were obtained and were found in reasonable agreement with the
      established values. The nose has a scrubbing effect, which reduces the
      concentration in the lungs in normal mice. n-Pentanol, sec-butanol and tert
      pentanol decreased tidal volume in normal mice, explained either by an activation
      of receptors in the upper airways or by a sensitization of the stretch receptors.
      Two types of pulmonary responses were seen in tracheal-cannulated mice, which
      could be explained by an effect on stretch receptors and another type of lung
      receptors.

PMID- 8160208
TI  - Inhalation of resuspended road dust, but not ammonium nitrate, decreases the
      expression of the pulmonary macrophage Fc receptor.
AB  - Pulmonary macrophages (PM) play a key role in the immune defenses of the lung.
      When stimulated, PM express Fc receptors (FcR) that regulate the immune response.
      PM were assayed for FcR expression following subchronic inhalation exposure of
      adult Fischer 344 rats to either 90 micrograms/m3 nitrate (NH4NO3), 300
      micrograms/m3 road dust, or clean air, for 4 h/day, 4 days/week, for 8 weeks. PM
      were lavaged from the lungs and attached to glass coverslips for 18 h. PM FcR
      were labelled with rat IgG conjugated with cyanine-3. For each exposure, FcR were
      determined with a Meridian ACAS 570 confocal cytometer by imaging the
      fluorescence of 50 cells. We found that the IgG binding to FcR (in arbitrary
      fluorescence units, FU, per cell) for PM from road dust exposed rats was less
      (835 +/- 39.3 FU/cell) than that for PM from both ammonium nitrate or clean air
      exposed rats (1115 +/- 58.0 FU/cell and 1123 +/- 46.6 FU/cell, respectively).
      While acid incubation conditions in vitro (pH 5.5 for 30 min to simulate the acid
      environment of ammonium nitrate inhalation) resulted in a 16% decrease in IgG
      binding (P < 0.05), IgG binding to PM from acid aerosol exposed rats was no
      different than the IgG bound to PM from clean air-exposed rats. PM exposed to
      road dust in vivo expressed 25% fewer FcR (P < 0.05). Three-dimensional images of
      PM failed to show any major alterations in FcR distribution. These preliminary
      results indicate cellular recognition of antibody-immune complexes may be
      impaired by subchronic exposure to road dust, which could decrease the immune
      response of road dust exposed animals.

PMID- 8160209
TI  - Serum bone-type alkaline phosphatase activity in women living in a cadmium
      polluted area.
AB  - To clarify the significance of elevated serum total alkaline phosphatase activity
      (t-ALP) in persons exposed to environmental cadmium (Cd), the fraction of ALP
      originating from bone (b-ALP) was assayed using a wheat-germ agglutinin method in
      23 men and 20 women in a Cd-polluted area who showed excessive urinary beta 2
      microglobulin excretion, and in 21 men and 44 women in a non-polluted area, in
      addition to 7 patients with itai-itai disease. The fraction of b-ALP increased
      linearly with the increase in t-ALP in the women, irrespective of Cd-exposure.
      Elevations of both t-ALP and b-ALP in the Cd-exposed women, including inhabitants
      of the Cd-polluted area and patients with itai-itai disease, were found with
      decreases in serum calcium and bone density. It is concluded that elevated serum
      ALP levels found in Cd-exposed persons reflect the development of Cd-induced bone
      damage.

PMID- 8160210
TI  - An investigation of activities and paraoxon sensitivities of hepatic aliesterases
      in beta-naphthoflavone-treated rats.
AB  - Aliesterases (carboxylesterases, EC 3.1.1.1) are serine esterases which may
      protect acetylcholinesterase during organophosphorus insecticide intoxication by
      providing alternative phosphorylation sites. Levels of hepatic aliesterase
      activity were investigated after the intraperitoneal administration of beta
      naphthoflavone (BNF) to female rats using nine 4-nitrophenyl esters as substrates
      (including straight and branched chain aliphatic and aromatic esters) and 1
      naphthyl acetate. In addition, the in vitro sensitivities of aliesterases to
      inhibition by paraoxon, the active metabolite of the common insecticide
      parathion, were studied. Hepatic aliesterases from BNF-treated rats displayed
      lower activities than those from the controls with all substrates except 4
      nitrophenyl phenylbutyrate and isovalerate. The aliesterases from BNF-treated
      rats were more sensitive to paraoxon inhibition with 4-nitrophenyl
      phenylbutyrate, valerate, and butyrate. Esterases hydrolyzing 4-nitrophenyl
      butyrate, valerate, and branched chain esters were most sensitive to paraoxon
      inhibition while those hydrolyzing 4-nitrophenyl hexanoate and aromatic esters
      were least sensitive. The results suggested that BNF-induced changes in hepatic
      aliesterases could alter responses to organophosphates.

PMID- 8160211
TI  - Cytotoxicity of sulphur mustard on a human keratinocyte cell line: direct effects
      compared to conditioned-medium effects.
AB  - Direct toxic effects of sulphur mustard (SM) were compared to SM-conditioned
      medium effects in a human keratinocyte cell line. Cytotoxicity was evaluated by
      measurement of cell viability with the Neutral Red uptake assay. Culture directly
      exposed to SM exhibited cytotoxic dose-response curves after 24, 48 or 72 h.
      Inhibitory concentration 50 (IC50) appeared to be more than 10 times lower after
      72 h than the corresponding value after 24 h. In contrast, no cytotoxic activity
      was observed in media which were collected 4 h or 24 h after SM exposure. Cell
      viability was unchanged even if observation was extended to 48 h. Results
      suggested that SM cytotoxicity was not due to potential mediators secreted by
      human keratinocytes.

PMID- 8160212
TI  - Molecular modelling of cytochrome CYP1A1: a putative access channel explains
      differences in induction potency between the isomers benzo(a)pyrene and
      benzo(e)pyrene, and 2- and 4-acetylaminofluorene.
AB  - The present studies were undertaken to provide a rationale for the observation
      that benzo(a)pyrene and 2-acetylaminofluorene induce the hepatic CYP1A1 protein,
      whereas their non-carcinogenic isomers benzo(e)pyrene and 4-acetylaminofluorene
      are, at best, relatively very weak inducers. Using amino acid sequence alignment,
      a molecular model of the CYP1A1 was constructed by analogy to CYP101, the
      bacterial protein for which the 3-dimensional structure is known from X-ray
      crystallographic analysis. The putative structure of the active site of the
      CYP1A1 protein shows the presence of two phenylalanine residues preferentially
      aligned in parallel orientation, presumably functioning as a 'sieve' for planar
      molecules, the established substrates of CYP1A1. The molecular dimensions of this
      putative access channel show a width and depth of 8.321 and 3.261 A,
      respectively. The width of 4-acetylaminofluorene, 8.794 A, and benzo(e)pyrene,
      9.153 A, precludes their passage through this channel access in contrast to
      benzo(a)pyrene and 2-acetylaminofluorene having a width of 7.150 and 5.283 A,
      respectively, explaining their difference in CYP1A1 induction potential.

PMID- 8160213
TI  - Extracellular dopamine levels within the striatum increase during inhalation
      exposure to toluene: a microdialysis study in awake, freely moving rats.
AB  - An exposure chamber for microdialysis on awake, freely moving rats during
      exposure to volatile agents is described. Inhalation exposure to 1000 and 2000
      ppm toluene for 2 h was accompanied by an increase in extracellular dopamine
      levels within the striatum, but did not affect the homovanillic acid level.
      Neither the dopamine nor the homovanillic acid level was affected by toluene 500
      ppm or isoamylacetate. It is suggested that the action of inhaled toluene on the
      dopamine neuron differs from that of the anaesthetic halothane, possibly by
      interfering with dopamine reuptake. Microdialysis seems to be a useful tool for
      studying the effects of volatile agents on brain neurotransmission.

PMID- 8160214
TI  - Protection by indomethacin against the lethality and hepatotoxicity of phalloidin
      in mice.
AB  - The present study examined the possible involvement of endogenous cyclooxygenase
      derived factors in the lethality and hepatic hemorrhagic necrosis induced by
      phalloidin. Mice were pretreated with indomethacin, aspirin or ibuprofen (all
      inhibitors of cyclooxygenase) and injected with phalloidin (2 mg/kg). The toxin
      induced 75% lethality and caused severe hemorrhagic necrosis of the liver
      associated with increased serum levels of AST and ALT. Indomethacin completely
      prevented the mortality and hepatic damage elicited by phalloidin as judged by
      morphologic analysis and serum AST and ALT release. The in vitro addition of
      indomethacin to suspensions of freshly-isolated hepatocytes decreased plasma
      membrane bleb formation induced by phalloidin. In contrast to indomethacin,
      aspirin and ibuprofen did not influence phalloidin toxicity in vivo. These
      results suggest that inhibition of prostanoids per se may not be the sole
      mechanism of protection by indomethacin.

PMID- 8160215
TI  - Induction of enoyl-CoA hydratase by LD50 exposure to perfluorocarboxylic acids
      detected by two-dimensional electrophoresis.
AB  - The effect of in vivo exposure to perfluoro-n-octanoic and perfluoro-n-decanoic
      acids was examined in the rat liver by two-dimensional electrophoresis (2DE).
      Using nonequilibrium pH-gradient electrophoresis in the first dimension
      separation, proteins associated with the mitochondrial/peroxisomal cell fraction
      were observed and immunologically identified. Conspicuous inductions in
      peroxisomal enoyl-CoA hydratase and other proteins of the peroxisomal beta
      oxidative pathway were observed following single-dose exposure to each compound.
      The abundance of the tentatively-identified mitochondrial equivalent, crotonase,
      was not altered by these intoxications. These results confirm previous
      observations of perfluorocarboxylic acid toxicity and support the use of 2D
      protein-pattern alterations in biomarker research. The ability to identify this
      type of alteration via 2DE, in association with specific toxic effects by
      chemically related compounds, may provide new and additional markers for chemical
      induced tissue damage.

PMID- 8160216
TI  - Effects of exposure to nicotine and to sidestream smoke on pregnancy outcome in
      rats.
AB  - Nicotine-delivering transdermal patches were applied to the back of timed
      pregnant Sprague-Dawley rats. Pregnancy failure was 100% in animals exposed to
      3.5 mg of nicotine per day during the entire pregnancy and 50% in animals exposed
      to the same amount during the first trimester. Application of 1.75 mg of nicotine
      per day resulted in a 50% pregnancy failure when exposure occurred during the
      entire pregnancy. In animals exposed for the first half of pregnancy to cigarette
      sidestream smoke, under conditions where plasma nicotine levels reached about 25%
      of those observed following exposure to 1.75 mg of nicotine per day, the average
      litter size was reduced by about 25%. It is concluded that continuous exposure to
      nicotine early during pregnancy may adversely affect pregnancy outcome in rats.

PMID- 8160217
TI  - Cardiac prognosis of patients with carotid stenosis and no history of coronary
      artery disease. Veterans Affairs Cooperative Study Group 167.
AB  - BACKGROUND AND PURPOSE: Patients with carotid stenosis have a high frequency of
      asymptomatic coronary artery disease (CAD). The purpose of this study of patients
      with asymptomatic carotid stenosis was to test the hypothesis that patients
      without a history of CAD have the same cardiac prognosis as patients with a
      history of CAD. METHODS: Men enrolled in the Department of Veterans Affairs study
      on the efficacy of carotid endarterectomy for asymptomatic carotid stenosis
      underwent a baseline cardiac evaluation (history, physical examination, and
      electrocardiogram) to document previous angina or myocardial infarction. Patients
      were randomized to medical therapy alone or medical therapy and carotid
      endarterectomy. Medical therapy consisted of aspirin 650 mg twice daily and
      treatment of risk factors. All episodes of angina, myocardial infarction, or
      sudden death during follow-up (average of 47.9 months) were recorded. RESULTS: Of
      444 men enrolled in the study, 200 (45%) had a history of CAD. During the study
      86 (43%) of 200 patients with CAD and 81 (33%) of 244 patients without a history
      of CAD had cardiac ischemic events (P = .03). In patients without a history of
      CAD, the first cardiac event was myocardial infarction or sudden death in 45
      patients (56%). Factors that were independently associated with cardiac events in
      patients without a history of CAD were diabetes (odds ratio [OR], 2.14; 95%
      confidence interval [CI], 1.15 to 3.97), intracranial occlusive disease (OR,
      2.13; 95% CI, 1.13 to 4.02), and peripheral vascular disease (OR, 2.04; 95% CI,
      1.14 to 3.66). Forty-two percent of patients with two of these factors and 69% of
      patients with all three factors had cardiac events. CONCLUSIONS: Men with carotid
      stenosis and no history of CAD have a lower rate of cardiac events than men with
      carotid stenosis who have a history of CAD. However, a subgroup of patients with
      carotid stenosis and no history of CAD who have coexistent intracranial occlusive
      disease, diabetes, or peripheral vascular disease have a risk of cardiac events
      similar to that of patients with a history of CAD.

PMID- 8160218
TI  - Increase in extracranial atherosclerotic carotid lesions in patients with brain
      ischemia in Japan. An angiographic study.
AB  - BACKGROUND AND PURPOSE: Atherosclerotic lesions in the cerebral arteries are
      distributed heterogeneously among different races. Intracranial carotid lesions
      are reported to be more common than extracranial carotid lesions among Japanese
      people, which is in sharp contrast to the pattern of cerebral atherosclerosis in
      whites. However, several Japanese clinicians have the impression, which has yet
      to be clinically proven, that extracranial carotid diseases are recently
      increasing in number. METHODS: One hundred twenty-one patients who developed
      ischemic stroke and underwent angiography were examined in the study. Seventy
      were admitted to our clinic from 1963 to 1965 (early group); the remaining 51
      patients were seen from 1989 to 1993 (recent group). Angiographic findings and
      vascular risk factors were compared between the two groups. RESULTS: Severe
      atherosclerotic lesions of the extracranial internal carotid arteries increased
      significantly during the ensuing 24 years between the end of the first period
      until the beginning of the second period (from 1965 to 1989), whereas lesions in
      the intracranial carotid system were similar between the two groups. Severe
      atherosclerosis in the extracranial internal carotid artery was more frequent in
      patients with diabetes mellitus, which proved to be the only risk factor that
      showed a temporal increase. CONCLUSIONS: The proportion of severe atherosclerosis
      in Japanese patients with brain ischemia has been increasing in the extracranial
      internal carotid artery, while that in the intracranial carotid system remains
      unchanged. Such a temporal change may be the result, at least in part, of an
      increase in the prevalence of diabetes mellitus.

PMID- 8160219
TI  - Paradoxical embolism as a cause of ischemic stroke of uncertain etiology. A
      transcranial Doppler sonographic study.
AB  - BACKGROUND AND PURPOSE: This study was designed to test the hypothesis that
      paradoxical embolization would be a cause of embolic strokes and transient
      ischemic attacks in patients with stroke of uncertain etiology in all age groups.
      METHODS: Thirty patients who had stroke of uncertain etiology were studied. They
      were divided into the following three groups: 13 patients with sudden onset
      (group A), 11 patients with subacute onset (group B), and 6 asymptomatic stroke
      patients (group C). Eleven patients with stroke of obvious etiology (group D) and
      11 normal healthy volunteers (group E) were also studied as controls. In all
      patients transcranial Doppler sonography and contrast echocardiography were
      recorded simultaneously after intravenous injection of the contrast medium.
      Findings of positive patient foramen ovale in contrast echocardiography or
      "chirp" sounds in transcranial Doppler sonography were defined as positive for
      paradoxical contrast embolization. Radioisotope phlebography of the lower
      extremities and pulmonary scintigraphy, using technetium-99 macroaggregated
      albumin, were performed in all 17 patients who had positive findings of
      paradoxical contrast embolization and in 12 patients whose findings were
      negative. RESULTS: Positive findings of paradoxical contrast embolization were
      found in 17 subjects by transcranial Doppler sonography but in only 8 on contrast
      echocardiography. These positive findings were detected more frequently in group
      A (77%) than in groups B, D, and E (9%, 18%, and 9%, respectively) (P < .05). In
      group C, 4 of 6 patients (67%) had positive findings. There were positive
      findings on both phlebography and pulmonary scintigraphy only in 6 group A
      patients, with positive findings of paradoxical contrast embolization.
      CONCLUSIONS: Transcranial Doppler sonography is a sensitive detector of right-to
      left shunts. Paradoxical cerebral embolization might be frequent in patients with
      stroke of unknown etiology, especially when the stroke is of sudden onset.

PMID- 8160220
TI  - Cardiac sources of embolism in patients with pial artery infarcts and lacunar
      lesions.
AB  - BACKGROUND AND PURPOSE: On the assumption that the majority of lacunes are caused
      by small-vessel diseases and that pial artery infarcts arise from cardio-embolic
      or large-vessel diseases, 194 patients from the Berlin Cerebral Ischemia Data
      Bank with either lacunar or pial artery infarcts were analyzed for the frequency
      of cardiac sources of embolism. The primary hypothesis was that the frequency of
      cardiac sources of embolism is higher among pial artery infarct subjects.
      METHODS: The presence of cardiac sources of embolism was estimated by
      electrocardiographic and transthoracic and transesophageal echocardiographic
      studies. Cranial computed tomography scans were evaluated by two masked
      observers. RESULTS: The overall rate of cardiac sources of embolism did not
      differ significantly between the lacunar and the pial artery infarct group (66%
      versus 71%; odds ratio, 0.80; confidence interval, 0.43 to 1.50).
      Echocardiographic evidence of cardiac thrombi was positively associated with pial
      artery infarcts (odds ratio, 0.18; confidence interval, 0.04 to 0.80); atrial
      fibrillation and all other cardiac sources were not. CONCLUSIONS: Left cardiac
      thrombi are significantly associated with pial artery infarcts. Other presumed
      cardiac sources of embolism, including atrial fibrillation, may often represent
      coincidental findings or have a less strong tendency to result in pial artery
      infarcts.

PMID- 8160221
TI  - Patent foramen ovale and brain infarct. Echocardiographic predictors, recurrence,
      and prevention.
AB  - BACKGROUND AND PURPOSE: Paradoxical embolism through a patent foramen ovale is a
      recognized cause of stroke, but clinical predictors, recurrence rate, and
      prevention of brain infarcts in patients with patent foramen ovale have not been
      determined. We reviewed transesophageal echocardiographic records to ascertain
      echocardiographic predictors and optimal prophylaxis for patent foramen ovale
      related infarcts. METHODS: A patent foramen ovale was identified in 74 patients
      during 615 transesophageal echocardiograms by color Doppler or saline contrast
      during a 60-month period. On the basis of final clinical situation, the patients
      were divided into the following groups: group 1, infarct with patent foramen
      ovale a likely cause (n = 16); group 2, infarct with patent foramen ovale an
      unlikely cause (n = 23); and group 3, no infarct (n = 35). Transesophageal
      echocardiograms were reviewed to assess patent foramen ovale characteristics and
      associated cardio-embolic sources without knowledge of clinical details or group
      assignment. Follow-up after a patent foramen ovale-related infarct was obtained
      by telephone or written correspondence in 15 of 16 group 1 patients. RESULTS:
      Atrial septal aneurysms were more common in group 1 (38%) compared with group 2
      (10%) and group 3 (8%) (P = .02). Contrast right-to-left shunting occurred in 88%
      of group 1 (P = .06) and 86% of group 2 (P = .07) compared with 60% of group 3.
      Prevention of recurrence in subjects with presumed patent foramen ovale-related
      brain infarcts varied. Aspirin was usually chosen after initial brain ischemia.
      Warfarin and patent foramen ovale closure were usually reserved for subjects with
      symptoms of brain ischemia while taking aspirin or those who required warfarin or
      cardiac surgery for other indications. No recurrent infarcts occurred in 15
      patients during a mean follow-up period of 28 months. CONCLUSIONS: Atrial septal
      aneurysm and right-to-left shunt may be predictive of a patent foramen ovale that
      predisposes a patient to stroke. Aspirin may provide sufficient infarct
      prophylaxis after initial ischemia. Warfarin and surgical correction should
      likely be reserved for those in whom aspirin is not effective or those who
      require warfarin or cardiac surgery for other reasons until prospective studies
      are available.

PMID- 8160222
TI  - Cardiovascular autonomic reflexes in brain infarction.
AB  - BACKGROUND AND PURPOSE: Increased sympathetic activity is associated with
      cardiovascular complications in stroke, but the role of the parasympathetic
      nervous system has not been carefully outlined. In the present study our purpose
      was to assess quantitatively autonomic cardiovascular disturbances in brain
      infarction by measuring cardiovascular autonomic reflexes. METHODS: We studied
      the autonomic regulation of cardiovascular functions prospectively in 40 patients
      with brain infarction (acute phase, 1 month, and 6 months) and in 55 healthy
      control subjects by recording heart rate and blood pressure responses to normal
      and deep breathing, the Valsalva maneuver, tilting, and isometric work. RESULTS:
      In the acute phase, heart rate responses to normal breathing, deep breathing, the
      Valsalva maneuver, and tilting were significantly (P < .05) impaired in both
      hemispheric and brain stem infarctions, thus indicating hypofunction of the
      parasympathetic nervous system. At 1 month heart rate responses to normal
      breathing (brain stem, P < .05), the Valsalva maneuver (brain stem, P < .01), and
      tilting (hemispheric, P < .05) were still significantly lower than those of the
      control subjects, but at 6 months significant suppression of the response was
      found only in tilting (hemispheric, P < .05). CONCLUSIONS: These findings suggest
      that in addition to the previously well-established sympathetic hyperfunction,
      brain infarction also seems to cause parasympathetic hypofunction, brain which
      may be involved in cardiovascular and other known manifestations of autonomic
      failure associated with stroke.

PMID- 8160223
TI  - Background factors and clinical symptoms of major depression with silent cerebral
      infarction.
AB  - BACKGROUND AND PURPOSE: We previously reported that major depression developing
      during or after the presenile period is frequently combined with silent cerebral
      infarction and that these patients have a high risk of stroke. Therefore, we
      investigated whether the background factors and clinical symptoms of patients
      with major depression with silent cerebral infarction [SCI(+)] different from
      those in patients with major depression without silent cerebral infarction [SCI(
      )] before medical treatment. METHODS: Patients with major depression with onset
      after 50 years of age were classified based on magnetic resonance imaging
      findings into the SCI(+) (n = 37) or SCI(-) (n = 20) group. The diagnostic
      criteria for major depression were those of the American Psychiatry Association
      (DSM-III-R). Patients with stroke or focal neurological symptoms were excluded.
      The SCI(+) group was subclassified according to whether the infarction area was
      perforating, cortical, or mixed artery. Family history of affective disorder,
      risk factors for stroke, and Zung's Self-rated Depression Scale (SDS) score
      before medical treatment of the group were compared. RESULTS: The SCI(+) group
      had a significantly lower (P < .05) frequency of family history of affective
      disorder but a significantly higher (P < .01) frequency of hypertension than did
      the SCI(-) group. The mean SDS score in the SCI(+) group was significantly higher
      than that in the SCI(-) group (P < .01). The mean SDS score of the mixed artery
      infarction group was higher than that of the perforating artery infarction group
      (P < .05). CONCLUSIONS: Patients with major depression with silent cerebral
      infarction present more marked neurological factors and more severe depressive
      symptoms than do those without silent cerebral infarction. Because these features
      were more prominent in the patients with mixed artery infarction with broad
      obstructions, we consider that the area of brain damage caused by cerebral
      infarction is positively related to the severity of depressive symptoms.

PMID- 8160224
TI  - Comparison of probability of stroke between the Copenhagen City Heart Study and
      the Framingham Study.
AB  - BACKGROUND AND PURPOSE: We wished to test the validity of a stroke probability
      point system from the Framingham Study for a sample of the population of
      Copenhagen, Denmark. In the Framingham cohort, the regression model of Cox
      established the effect on stroke of the following factors: age, systolic blood
      pressure, the use of antihypertensive therapy, diabetes mellitus, cigarette
      smoking, prior cardiovascular disease, atrial fibrillation, and left ventricular
      hypertrophy. Derived from this model, stroke probabilities were computed for each
      sex based on a point system. The authors claimed that a physician can use this
      system for individual stroke prediction. METHODS: The Copenhagen City Heart Study
      is a prospective survey of 19,698 women and men aged 20 years or older invited to
      two cardiovascular examinations at 5-year intervals. The baseline examination
      included 3015 men and 3501 women aged 55 to 84 years; 474 stroke events occurred
      during 10 years of follow-up. In both cohorts initial cases of stroke and
      transient ischemic attack recorded during 10 years of follow-up were used. We
      used the statistical model from the Framingham Study to establish a corresponding
      stroke probability point system using data from the Copenhagen City Heart Study
      population. We then compared the effects of the relevant risk factors, their
      combinations, and the corresponding stroke probabilities. We also assessed stroke
      events during 10 years of follow-up in several subgroups of the Copenhagen
      population with different combinations of risk factors. RESULTS: For the
      Copenhagen City Heart Study population some of the risk factors (diabetes
      mellitus, cigarette smoking, atrial fibrillation, and left ventricular
      hypertrophy) had regression coefficients different from those of the Framingham
      Study population. Consequently, the probability of stroke for persons presenting
      these risk factors and their combinations varied between the two studies. For
      some other risk factors (age, blood pressure, and cardiovascular disease), no
      major differences were found. The recorded frequency of stroke events in
      subgroups of the Copenhagen population was compatible with the estimated
      probability intervals of stroke from the Copenhagen City Heart Study and with
      those from the Framingham Study, but these intervals were very large.
      CONCLUSIONS: The majority of risk factors for stroke identified by the Framingham
      Study also had a significant effect in the Copenhagen City Heart Study
      population. The differences found could be due partly to different definitions of
      these factors used by the two studies. Although estimated stroke probabilities
      based on point systems from the Copenhagen City Heart Study and the Framingham
      Study were similar, the points scored in the two systems did not always
      correspond to the same combination of risk factors. Such systems can be used for
      estimating stroke probability in a given population, provided that the
      statistical confidence limits are known and the definitions of risk factors are
      compatible. However, because of the large statistical uncertainty, a prognostic
      index should not be applied for individual prediction unless it is used as an
      indicator of high relative risk associated with the simultaneous presence of
      several risk factors.

PMID- 8160225
TI  - The influence of age on stroke outcome. The Copenhagen Stroke Study.
AB  - BACKGROUND AND PURPOSE: This study was undertaken to elucidate whether and how
      age influences stroke outcome. METHODS: This prospective and community-based
      study comprised 515 consecutive acute stroke patients. Computed tomographic scan
      was performed in 79% of patients. Activities of daily living (ADL) and
      neurological status were assessed weekly during hospital stay using the Barthel
      Index (BI) and the Scandinavian Stroke Scale (SSS), respectively. Information
      regarding social condition and comorbidity before stroke was also registered. A
      multiple regression model was used to analyze the independent influence of age on
      stroke outcome. RESULTS: Age was not related to the type of stroke lesion or
      infarct size. However, age independently influenced initial BI (-4 points per 10
      years, P < .01), initial SSS (-2 points per 10 years, P = .01), and discharge BI
      (-3 points per 10 years, P < .01). No independent influence of age was found
      regarding mortality within 3 months, discharge SSS, length of hospital stay, and
      discharge placement. ADL improvement was influenced independently by age (-3
      points per 10 years, P < .01), whereas age had no influence on neurological
      improvement or on speed of recovery. CONCLUSIONS: Age independently influences
      stroke outcome selectively in ADL-related aspects (BI) but not in neurological
      aspects (SSS), suggesting a poorer compensatory ability in elderly stroke
      patients. Therefore, rehabilitation of elderly stroke patients should be focused
      more on ADL and compensation rather than on the recovery of neurological status,
      and age itself should not be a selection criterion for rehabilitation.

PMID- 8160226
TI  - Elevated serum cholesterol is a risk factor for both coronary heart disease and
      thromboembolic stroke in Hawaiian Japanese men. Implications of shared risk.
AB  - BACKGROUND AND PURPOSE: The relation between total serum cholesterol level and
      thromboembolic or nonhemorrhagic stroke is controversial. The Honolulu Heart
      Program cohort of Japanese-American men provides data which show that elevated
      serum cholesterol is an independent predictor of thromboembolic stroke as well as
      coronary heart disease (CHD). The data are presented to suggest that the
      association of elevated cholesterol with stroke is sometimes underestimated or
      underreported partly because of competing or shared risk with CHD, the other
      major atherosclerotic end point. METHODS: The data are based on 6352 men (aged 51
      to 74 years) at baseline examination (1971 to 1974) who were free of clinical CHD
      and stroke and were followed an average of 15 years for new cases of both end
      points. Relative risks of serum cholesterol for CHD and thromboembolic stroke
      were calculated, controlling for other major cardiovascular covariates. RESULTS:
      There was a continuous and progressive increase in both CHD and thromboembolic
      stroke rates with increasing levels of serum cholesterol. The relative risk
      between the highest and lowest quartiles of serum cholesterol was 1.7 (95%
      confidence interval, 1.4 to 2.0) for CHD and 1.4 (95% confidence interval, 1.1 to
      1.9) for thromboembolic stroke. There was a decline in the difference in relative
      risks between CHD and thromboembolic stroke in older men (aged 60 years and
      older) compared with younger men (aged younger than 60 years). CONCLUSIONS: These
      data provide additional evidence that elevated serum cholesterol should be
      considered a primary risk factor for thromboembolic stroke, presumably through
      its effect on both coronary and cerebrovascular atherosclerosis. It is suggested
      that this association is sometimes underestimated or underreported partly because
      of shared or competing risk with CHD, the clinical manifestation of
      atherosclerosis that generally occurs earlier in life and with greater frequency
      than thromboembolic stroke.

PMID- 8160227
TI  - The influence of stroke unit rehabilitation on functional recovery from stroke.
AB  - BACKGROUND AND PURPOSE: Shorter lengths of hospital stay in stroke units could be
      due to quicker functional recovery or mechanisms of expediting hospital
      discharge. METHODS: Stroke survivors with an intermediate prognosis at 2 weeks
      after stroke (n = 146) were randomized for management in a stroke rehabilitation
      unit or in general wards. Barthel scores were monitored at weekly intervals until
      hospital discharge. The duration and type of physiotherapy and occupational
      therapy received by patients in either setting were also recorded. The rate of
      change of Barthel scores, therapy input, and the duration of hospital stay were
      compared between the two settings. RESULTS: Neurological deficits and median
      initial Barthel scores were comparable between patients in the stroke unit (n =
      73) and general wards (n = 68). Median discharge Barthel score of patients
      managed in the stroke unit was significantly higher than that of patients managed
      in general wards (15 versus 12). Median Barthel scores in the stroke unit group
      rose rapidly after 2 weeks, reaching a plateau at 6 weeks. The change in median
      Barthel score in patients in general wards was significantly slower, reaching a
      plateau at 12 weeks despite similar therapy input. There was a significant delay
      in discharging stroke patients in general wards (20 weeks) compared with those in
      the stroke unit (6 weeks). CONCLUSIONS: Functional recovery is significantly
      greater and more rapid in a stroke rehabilitation unit compared with general
      wards despite similar therapy input. These units also shorten hospital lengths of
      stay by expediting appropriate discharges.

PMID- 8160228
TI  - Comparison of carbon dioxide responsiveness of cerebellar blood flow between
      affected and unaffected sides with crossed cerebellar diaschisis.
AB  - BACKGROUND AND PURPOSE: Concerning vasoreactivity of cerebellar blood flow (CeBF)
      in patients affected with crossed cerebellar diaschisis (CCD), several
      controversies have been reported. One is reduced asymmetry of CeBF after
      acetazolamide administration in 99mTc hexamethylpropyleneamine oxime single
      photon emission-computed tomography, and the other is persistent asymmetry with
      alternation in PaCO2 using the 133Xe clearance method. The purpose of this study
      is to examine whether CeBF vasoreactivity in the side affected with CCD is the
      same as that in the unaffected side. METHODS: We analyzed CeBF during hypocapnia,
      normocapnia, and hypercapnia performed in 27 patients with cerebrovascular
      disease (age range, 38 to 73 years; mean age, 62.0 +/- 8.5 years) affected by
      CCD. CeBF was measured using H2(15)O and positron emission tomography. RESULTS:
      The CeBF ratio of CCD-affected side to CCD-unaffected side was consistent during
      the perturbation of PaCO2. This ratio was 0.82 +/- 0.08 for PaCO2 elevation and
      0.83 +/- 0.07 for PaCO2 lowering. Both were not significantly different from
      unity. CONCLUSIONS: The percent change of CeBF per millimeter of mercury PaCO2
      change was uniform across affected and unaffected sides with CCD. These findings
      are consistent with our recent findings observed in activated cerebral tissue
      during photic stimulation.

PMID- 8160229
TI  - Regional cerebral blood flow in familial hypercholesterolemia.
AB  - BACKGROUND AND PURPOSE: Although epidemiologic investigations are trying to
      clarify the role of plasma lipid concentrations (primarily cholesterol and its
      subfractions) as risk factors for both ischemic and hemorrhagic stroke, little
      information is available regarding the effect of sustained hypercholesterolemia
      on cerebral perfusion. METHODS: Regional cerebral blood flow (CBF) was measured
      by the 133Xe inhalation method in 25 heterozygous patients (four untreated)
      affected with familial hypercholesterolemia. In 15 patients regional CBF was
      repeated 20 minutes after intravenous administration of acetazolamide (10 mg/kg
      body wt) to evaluate cerebrovascular reactivity. Correlations among cerebral
      perfusion data, present or pretreatment plasma lipid concentrations, and certain
      other clinical features were assessed by ANOVA. RESULTS: Both basal regional CBF
      and cerebrovascular reactivity were normal in the vast majority of patients
      compared with age- and sex-matched normal control subjects. CBF was significantly
      dependent on pretreatment low-density lipoprotein cholesterol (LDL-C)
      concentration (P = .005) and the presence of symptomatic ischemic heart disease
      (P = .015). CBF was only slightly dependent on age (P = .05) and was not
      dependent on either lipoprotein(a) or present LDL-C concentration. CBF did not
      differ between treated and untreated patients, and the perfusional increase
      induced by acetazolamide was not related to any other variable. CONCLUSIONS:
      Cerebral perfusion and cerebrovascular reactivity were maintained within the
      normal range despite long-lasting, severe hypercholesterolemia, even if a
      somewhat lower CBF was found in those patients with the highest LDL-C
      pretreatment levels. These results are in accord with the epidemiologic data that
      implicate hypercholesterolemia as a minor risk factor, if a risk factor at all,
      for intracranial atherosclerosis and ischemic stroke.

PMID- 8160230
TI  - Anterior choroidal artery territory infarcts. Study of presumed mechanisms.
AB  - BACKGROUND AND PURPOSE: A previous study suggested that occlusive diseases of
      small penetrating arteries account for most anterior choroidal artery (AChA)
      territory infarcts, but half of the patients did not have an echocardiogram.
      Cases of AChA territory infarcts associated with internal carotid artery stenosis
      or atrial fibrillation suggest that this hypothesis may be wrong. The aim of this
      study was to determine the mechanism of 16 nonselected consecutive AChA territory
      infarcts. METHODS: The study population consisted of 8 men and 8 women aged 17 to
      89 years. They underwent a computed tomographic scan at the acute stage, Doppler
      ultrasonography and B-mode echotomography of the cervical arteries, bidimensional
      transthoracic echocardiography, and cerebral magnetic resonance imaging, replaced
      by a second computed tomographic scan in 3 patients. Ten patients underwent
      cerebral angiography. We defined the presumed cause of stroke according to the
      criteria used in the trial of Org 10172 in acute stroke treatment. RESULTS: The
      presumed cause of stroke was definite cardio-embolism in 4 patients (atrial
      fibrillation in 2, paradoxical embolism in 1, and left ventricular akinesia in
      1); definite large-vessel atherosclerosis in 2; dissection of the internal
      carotid artery in 2; and definite small-vessel occlusion in 1. Seven patients had
      a negative diagnostic workup. Six patients had no risk factors for small-vessel
      occlusion. The AChA was not visible on angiography in 4 patients. One patient had
      two arterial cutoffs, suggestive of emboli in other cerebral arteries.
      CONCLUSIONS: This study suggests that AChA territory infarcts are rarely related
      to small-vessel occlusion and therefore require a complete diagnostic workup.

PMID- 8160231
TI  - Diffusion-weighted imaging differentiates ischemic tissue from traumatized
      tissue.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging (MRI) has
      been shown to be particularly effective in detecting early (0 to 4 hours)
      pathophysiological changes in localized brain regions after cerebral ischemia.
      The present study sought to establish whether diffusion-weighted MRI would be
      similarly effective in predicting outcome after traumatic brain injury. METHODS:
      Diffusion-weighted MRI images and T2-weighted MRI images were obtained over 4
      hours after either moderate fluid percussion-induced traumatic brain injury or
      unilateral carotid ligation in rats. RESULTS: Diffusion-weighted MRI images of
      traumatic brain injury demonstrated focal regions of image hypointensity as early
      as 1 hour after trauma. The relative diffusion coefficient in these hypointense
      regions was significantly increased (P < .005) by 4 hours after trauma compared
      with the noninjured hemisphere, but only in the transverse plane in the x
      direction. In contrast, induction of diffuse, nonfocal ischemia by unilateral
      carotid ligation resulted in scattered regions of hyperintensity with a
      significant (P < .001) decrease in relative diffusion coefficient as early as 1
      hour after ligation compared with the noninjured hemisphere. This decrease
      exhibited no directionality. CONCLUSIONS: We conclude that traumatic brain injury
      results in an increased water diffusion distance with the directionality
      indicative of bulk flow of extracellular fluid toward the lateral ventricles
      (vasogenic edema). In contrast, the decreased water diffusion distance with no
      apparent directionality observed in ischemia is most likely indicative of
      cytotoxic edema. Diffusion-weighted MRI therefore has the potential to
      differentiate cases of traumatic brain injury with no focal ischemia from those
      instances of traumatic brain injury in which focal ischemia is a complication.

PMID- 8160232
TI  - p53-immunoreactive protein and p53 mRNA expression after transient middle
      cerebral artery occlusion in rats.
AB  - BACKGROUND AND PURPOSE: We investigated the temporal distribution of the p53
      immunoreactive protein in conjunction with cellular damage and the expression of
      the p53 mRNA after focal cerebral ischemia in rats. METHODS: Male Wistar rats (n
      = 66; controls, n = 7) were subjected to 2 hours of middle cerebral artery
      occlusion and were killed at various times of reperfusion (0.5 to 168 hours) for
      p53 immunohistochemistry and Northern blot analysis. RESULTS: A cellular
      expression of mutant p53-immunoreactive protein was found localized to anatomic
      sites exhibiting severe neuronal damage. A maximal induction of mutant p53
      immunoreactive protein was found at 12 hours after reperfusion and subsequently
      declined. No wild-type p53 protein expression was detected after ischemia. A time
      dependent expression of p53 mRNA was observed in both hemispheres. The peak level
      of p53 mRNA occurred at 24 hours after reperfusion. CONCLUSIONS: Our data
      indicate that the expressions of p53-immunoreactive protein and p53 mRNA are
      upregulated after transient focal cerebral ischemic insult in rats. The
      concomitant appearance of p53 and cell damage in ischemic brain suggests that p53
      expression may impact cell biological response to an ischemic insult.

PMID- 8160233
TI  - Superoxide dismutase ameliorates neuronal death from hypoxia in culture.
AB  - BACKGROUND AND PURPOSE: Studies showing efficacy with free radical scavengers
      have been conflicting, and when protection was demonstrated it was attributed to
      action at the level of the vascular endothelium. The purpose of this study was to
      test the hypotheses that neuronal free radical formation plays a role in the
      ischemic cascade and occurs intracellularly and that free radical scavengers, if
      taken up intracellularly, will protect against hypoxic damage. METHODS: A tissue
      culture model of hypoxia followed by restoration of oxygen was employed, using
      both superior cervical ganglia and hippocampal neurons. Cells were exposed to an
      anoxic atmosphere of 95% N2 and 5% CO2 and examined 2 to 24 hours later after
      restoration of oxygen. Determination of survival was measured by trypan blue
      exclusion. Nitroblue tetrazolium stain was used to assess free radical formation.
      RESULTS: Pretreatment with free superoxide dismutase did not decrease cell death
      after hypoxia as measured by trypan blue exclusion. However, when superoxide
      dismutase was taken up intracellularly under depolarizing conditions (55 mmol/L
      KCl in the medium), cell death was decreased significantly compared with hypoxic
      controls (28.7 +/- 4.34 versus 40.3 +/- 4.33; P < .03). During hypoxia neurons
      reduced nitroblue tetrazolium to form the blue precipitate formazan, and the
      color change was blocked in neurons pretreated with superoxide dismutase in
      depolarizing medium. Similar findings occurred in both superior cervical ganglia
      and hippocampal neurons. CONCLUSIONS: These findings provide evidence to support
      the role of neuronal free radical formation in cell death secondary to hypoxia.
      In addition, free radical scavengers, if taken up intracellularly, may partially
      ameliorate their deleterious effect.

PMID- 8160234
TI  - The role of superoxide anions in the pathogenesis of cerebral vasospasm.
AB  - BACKGROUND AND PURPOSE: To determine the role of superoxide anions in the
      pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage, we
      studied the preventive effect of human recombinant copper-zinc superoxide
      dismutase (h-r SOD) in a rabbit subarachnoid hemorrhage (SAH) model. METHODS:
      Forty-five rabbits receiving intracisternal injection of 3 mL autologous
      nonheparinized blood or 3 mL saline were divided into four groups as follows: (1)
      saline injected and no treatment (control group, n = 6); (2) blood injected and
      no treatment (SAH group, n = 20); (3) blood injected and treated by multiple
      intracisternal injections of 30,000 U of h-r SOD in 0.5 mL saline (SOD group, n =
      9); and (4) blood injected and treated by multiple intracisternal injections of
      0.5 mL saline (saline group, n = 10). Serial angiograms were performed after the
      blood injection, and the diameter of the basilar artery was measured. Three
      animals from the control group and five animals from the SAH and SOD groups each
      were killed 2 days after SAH, and their basilar arteries were processed for
      transmission electron microscopic observations. RESULTS: In the SAH and saline
      groups, the diameter of the basilar arteries was significantly reduced (28 +/-
      14% and 27 +/- 9%, respectively) at 2 days after the blood injection, then
      recovered to pre-SAH levels until 11 days. In the SOD group, the diameter of the
      basilar artery was only minimally changed during the follow-up period.
      Transmission electron microscopy revealed endothelial injury in all basilar
      arteries in the SAH group, whereas endothelial injury was minimal in the SOD
      group. CONCLUSIONS: We determined that h-r SOD prevents the occurrence of
      vasospasm, possibly as a result of preventing endothelial injury initiated by
      superoxide anions.

PMID- 8160235
TI  - Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell
      damage after transient middle cerebral artery occlusion in rats.
AB  - BACKGROUND AND PURPOSE: Postischemic cerebral inflammation may contribute to
      ischemic cell damage. The CD11b/18 (Mac-1) integrin mediates stimulated
      neutrophil binding to endothelia. We therefore investigated the effect of
      administration of an anti-Mac-1 monoclonal antibody on cerebral ischemic cell
      damage in the rat. METHODS: Rats (n = 10) were subjected to 2 hours of middle
      cerebral artery occlusion; the anti-Mac-1 antibody was administered at a dose of
      2 mg/kg i.v. at 1 hour of reperfusion and 1 mg/kg i.v. at 22 hours of reperfusion
      or an isotype-matched control antibody (n = 10) was administered using the same
      experimental protocol. Rats were killed at 46 hours of reperfusion, and brain
      sections were stained with hematoxylin and eosin for histological evaluation. In
      a separate population of rats given either vehicle (n = 8) or anti-Mac-1
      antibodies (n = 9), intraparenchymal neutrophils were measured by means of a
      myeloperoxidase assay. RESULTS: The lesion volume was significantly smaller (28%)
      in the anti-Mac-1 antibody group compared with the vehicle control group (P <
      .01). Numbers of intraparenchymal polymorphonuclear cells were significantly
      reduced (P < .05) in the cortex of the anti-Mac-1 antibody group compared with
      the vehicle control group. CONCLUSIONS: Our data demonstrate that administration
      of anti-Mac-1 antibody 1 hour after onset of reperfusion results in significant
      reductions of ischemic cell damage and intraparenchymal neutrophils after
      transient (2-hour) focal cerebral ischemia in the rat.

PMID- 8160237
TI  - Neurovascular manifestations of heritable connective tissue disorders. A review.
AB  - BACKGROUND: Heritable disorders of connective tissue are recognized in a small
      minority of patients with neurovascular diseases. In this report, we review the
      neurovascular manifestations of four heritable connective tissue disorders:
      Ehlers-Danlos syndrome, Marfan's syndrome, osteogenesis imperfecta, and
      pseudoxanthoma elasticum, as well as two other systemic disorders with potential
      vascular manifestations: neurofibromatosis and polycystic kidney disease. SUMMARY
      OF REVIEW: Typical neurovascular complications of Ehlers-Danlos syndrome are
      carotid-cavernous fistulae, intracranial aneurysms, and cervical artery
      dissections. Arterial dissections and intracranial aneurysms cause the majority
      of neurovascular symptoms in Marfan's syndrome. Neurovascular disease is uncommon
      in osteogenesis imperfecta, although carotid-cavernous fistulae and vertebral
      artery dissections have been reported. Neurovascular disease in pseudoxanthoma
      elasticum is characterized by intracranial aneurysms and cerebral ischemia caused
      by premature arterial occlusive disease. Intracranial occlusive arterial disease
      is the most common neurovascular manifestation of neurofibromatosis, followed by
      cervical arteriovenous fistulae and aneurysms and intracranial aneurysms.
      Intracranial aneurysms are the hallmark of polycystic kidney disease.
      CONCLUSIONS: Recognition of an underlying generalized connective tissue disorder
      may be of considerable importance, although marked phenotypic heterogeneity often
      complicates the diagnosis of these disorders. Conversely, the association of
      certain neurovascular anomalies with generalized connective tissue disorders and
      recognition of their basic molecular defect may offer clues to the etiology and
      pathogenesis of these neurovascular diseases in general.

PMID- 8160236
TI  - Middle cerebral artery occlusion due to hydatid cysts of myocardial and
      intraventricular cavity cardiac origin. Two cases.
AB  - BACKGROUND: Hemispheric strokes of hydatid origin are very rare. We describe two
      cases of middle cerebral artery occlusion by a cyst of cardiac origin. CASE
      DESCRIPTIONS: Cerebral angiography demonstrated occlusion of the initial segment
      of the middle cerebral artery. Myocardial and pericardial cysts were diagnosed by
      echography and pathological examination. Subsequent development of hydatid cysts
      within the necrotic area of the infarcted hemisphere suggests cerebral hydatid
      embolism of cardiac origin. CONCLUSIONS: In endemic areas, embolism of hydatid
      cysts should be considered in the diagnosis of stroke in young patients.

PMID- 8160238
TI  - Does endothelin-1 play a role in the pathogenesis of cerebral vasospasm?
AB  - BACKGROUND: Endothelin-1 is a very powerful endogenous vasoconstrictor substance
      produced by endothelial cells. Its long-lasting vasoconstrictor and hypertensive
      action has been well documented in several species, including humans. SUMMARY OF
      REVIEW: It is generally accepted that endothelin-1 may contribute to the
      pathogenesis of a number of cardiovascular diseases. In the cerebral vasculature,
      endothelin-1 has been proposed as a key mediator of cerebral vasospasm following
      subarachnoid hemorrhage. Availability of endothelin-1 antagonist provided a
      pharmacologic tool to test the role of endothelin in the development of
      vasospasm. CONCLUSIONS: This brief review is focused on the controversial results
      reported by different groups concerning the possible role of endothelin-1 in
      narrowing of cerebral arteries exposed to autologous blood.

PMID- 8160239
TI  - Cerebral hypoperfusion in stroke prognosis and brain recovery.

PMID- 8160240
TI  - Blood viscosity and cerebral blood flow.

PMID- 8160241
TI  - Does ticlopidine prevent reversible cerebrovascular ischemic events in women?

PMID- 8160242
TI  - Improving stroke rehabilitation: a controlled study.

PMID- 8160243
TI  - Migraine equivalent and hemorrhagic infarction.

PMID- 8160244
TI  - Major cerebral vessel occlusion in SLE due to circulating anticardiolipin
      antibodies.

PMID- 8160245
TI  - Headache in stroke: use of the international Headache Society classification.

PMID- 8160246
TI  - Lobar hemorrhages.

PMID- 8160247
TI  - A high-performance liquid chromatographic method for the simultaneous
      determination of venlafaxine and O-desmethylvenlafaxine in biological fluids.
AB  - A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC)
      method for simultaneous determination of venlafaxine (V) and O
      desmethylvenlafaxine (ODV) in plasma and urine has been developed. V and ODV are
      extracted from plasma using a liquid-liquid extraction procedure, chromatographed
      on a Supelcosil LC-8DB column, and quantitated by UV detection at 229 nm.
      Linearity was established over the range 10-500 ng/ml for V and 7.2-720 ng/ml for
      ODV using 1.0 ml of human, rat, dog, and mouse plasma. For urine, for both
      analytes, an analytical range 0.1-10.0 micrograms/ml was established. Accuracy of
      > +/- 10% about the theoretical mean was achieved for all matrices, with intra-
      and interday coefficients of variation for precision of < 10%. Endogenous
      components in plasma and/or urine or known metabolites of V do not interfere in
      the determination of the analytes. For both V and ODV a quantitation limit of 10
      ng/ml for plasma was adequate for their estimation over a period of three half
      lives, following administration of a pharmacologic dose in man, and the limit of
      0.1 microgram/ml, for urine, can monitor excretion of as little as 0.5% of the
      dose.

PMID- 8160248
TI  - Cerebrospinal fluid concentrations of caffeine following oral drug
      administration: correlation with salivary and plasma concentrations.
AB  - Twelve hospitalized adult patients received 300 mg of oral caffeine 1 h before a
      diagnostic lumbar puncture. Caffeine concentrations were determined
      simultaneously in saliva, plasma, and cerebrospinal fluid (CSF). Mean caffeine
      concentrations in plasma, saliva, and CSF were 5.9 +/- 2.1, 4.4 +/- 1.5, and 2.9
      +/- 1.1 micrograms/ml, respectively, with coefficients of correlation plasma
      saliva, saliva-CSF, and plasma-CSF of 0.89, 0.79, and 0.77, respectively, all
      statistically significant (p < 0.001).

PMID- 8160249
TI  - Kinetics of mercaptopurine and thioguanine nucleotides in renal transplant
      recipients during azathioprine treatment.
AB  - The purpose of this study was to examine the pharmacokinetics of mercaptopurine
      (6-MP) and thioguanine nucleotides (6-TGN) during azathioprine treatment. Plasma
      profiles and urinary excretion of 6-MP and 6-TGN concentrations in red blood
      cells (RBCs) were measured repeatedly during the first 3 weeks following
      transplantation in 10 adults, who had received kidney grafts from living related
      donors. Mean maximal 6-MP plasma concentration (Cmax) was 340 nmol/L (SD = 290),
      mean time to Cmax (Tmax) was 2 h (SD = 1.8), and mean area under the plasma
      concentration-time curve (AUC) was 930 nmol/L/h (SD = 770). The mean fraction of
      azathioprine dose excreted as 6-MP in urine was 1.32% (SD = 1.11). Up to
      eightfold variability of Cmax and AUC was observed from day to day within each
      patient. The correlation between 6-MP AUC and amount excreted in the urine was
      weak (r = 0.37, 95% CI from 0.02 to 0.64). In this group of patients the observed
      6-TGN levels in RBCs were low; maxima during the observation period ranged from
      undetectable to 250 pmol/8 x 10(8) RBCs. In individual patients, 6-TGN levels
      were relatively stable throughout the dosing interval ("within-dose-interval-CV"
      < 19%), even when sharp and high 6-MP peaks in plasma were observed.

PMID- 8160250
TI  - Radioimmunoassay for 7-hydroxy metabolite of fluphenazine and its application to
      plasma level monitoring in schizophrenic patients treated long term with oral and
      depot fluphenazine.
AB  - Immunization of New Zealand white rabbits with a bovine serum albumin conjugate
      of 7-hydroxy-N-carboxyethyl-N-deshydroxyethylfluphenazine produced highly
      specific antisera for 7-hydroxyfluphenazine (7-OHFLU). A radioimmunoassay (RIA)
      was developed using antisera from one of the rabbits that enabled for the first
      time the determination of plasma levels of 7-OHFLU, an active metabolite of
      fluphenazine (FLU), in patients treated with oral FLU dihydrochloride or i.m. FLU
      decanoate. The assay method provided sufficient sensitivity to determine
      accurately 20 pg of 7-OHFLU in 200 microliters (0.1 ng/ml) of plasma with a
      coefficient of variation of < 10%. The antiserum used in the RIA for 7-OHFLU
      demonstrated negligible cross-reactivity with FLU and its metabolites such as FLU
      sulfoxide, N-deshydroxyethylFLU, FLU N4'-oxide, N-deshydroxyethyl-7-OHFLU, and 7
      O-glucuronide of FLU and also with other antipsychotic agents and commonly
      coadministered drugs. The 7-OHFLU was present in measurable amounts in all plasma
      samples obtained at 4-week intervals from patients receiving a daily oral dose of
      5 (n = 10), 10 (n = 13), or 20 (n = 14) mg of FLU dihydrochloride. Large
      interindividual variations in the plasma level of FLU and 7-OHFLU were noted and
      the mean plasma levels ratios of 7-OHFLU/FLU at these doses were 2.07 +/- 1.08,
      2.07 +/- 1.13, and 2.02 +/- 0.82, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8160251
TI  - Important metabolites to measure in pharmacodynamic studies of chlorpromazine.
AB  - Plasma concentrations of chlorpromazine (CPZ) and six metabolites were measured
      in 12 chronic schizophrenic patients on a fixed dose of CPZ. All six metabolites
      were measured in significant concentrations, ranging from 12 to 57% of the parent
      drug concentration. They are listed in order of decreasing mean concentration as
      follows: chlorpromazine-N-oxide > chlorpromazine sulfoxide > 7-OH chlorpromazine
      > Nor2 chlorpromazine sulfoxide > Nor2 chlorpromazine > Nor1 chlorpromazine. CPZ
      concentrations showed significant correlation with the 7-OH chlorpromazine
      metabolite concentration. Since these metabolites have been associated with in
      vitro activity and occur in significant concentrations, it is recommended that
      all six metabolites be measured in studies correlating drug levels with
      pharmacodynamic effects.

PMID- 8160252
TI  - Bayesian forecasting of serum vancomycin concentrations with non-steady-state
      sampling strategies.
AB  - The application of three non-steady-state sampling strategies and the fitting of
      either three or five pharmacokinetic parameter estimates by a two-compartment
      Bayesian forecasting program was evaluated retrospectively in 27 adult patients
      with stable renal function. Sampling strategies included a single midpoint
      concentration, a set of peak and trough concentrations, and three serial
      vancomycin concentrations. The most precise and least-bias predictions of steady
      state peak vancomycin concentrations were observed by using population-based
      parameter estimates [mean prediction error (ME) = -0.40 and mean absolute error =
      5.77]. The addition of non-steady-state feedback concentration(s) did not provide
      additional information for predictions of future steady-state peak
      concentrations. The least-bias prediction of steady-state trough vancomycin
      concentrations was seen when a single midpoint non-steady-state concentration was
      used (ME = 0.92 and -0.17 for five and three fitted parameter estimates,
      respectively). The MEs of serial and peak and trough feedback strategies were
      similar in magnitude to those obtained using population parameters, but in
      opposite directions (underprediction vs. overprediction, respectively). The
      fitting of only three parameters produced results similar to those using five
      parameters. The results from this study confirm our previous evaluation that non
      steady-state concentrations provide very minimal information to Bayesian
      forecasting of future steady-state concentrations.

PMID- 8160253
TI  - Probable metabolic interaction between methadone and fluvoxamine in addict
      patients.
AB  - We report five cases where fluvoxamine (FLVX) was added to maintenance treatment
      with methadone (MTD) in addict patients with affective disorders. In view of the
      implication of FLVX in several metabolic drug interactions, MTD plasma levels
      were measured before and after treatment with FLVX. A slight increase
      (approximately 20% of the MTD plasma level/dose ratio) occurred in two cases. In
      the remaining three patients, the interaction was more pronounced (40-100%
      increase of the MTD plasma level/dose ratio), with clinical manifestations of
      opiate withdrawal after stopping FLVX therapy in one case. Caution is needed when
      starting or stopping treatment with FLVX in patients receiving maintenance
      treatment with methadone.

PMID- 8160254
TI  - Serum digoxin levels after concomitant ticarcillin and clavulanic acid
      administration.
AB  - Recently it has been recognized that steady-state serum digoxin concentrations
      may increase or fall to ineffective levels when the glycoside is administered
      together with several antibiotics. Our study was designed to assess if serum
      digoxin levels may be modified by the concomitant use of a ticarcillin and
      clavulanic acid. The study was carried out in 15 hospitalized patients suffering
      from exacerbation of their chronic bronchitis without liver disease and renal
      failure. Serum digoxin levels were not significantly modified by the concomitant
      use of a ticarcillin and clavulanic acid, although peak digoxin serum
      concentrations were slightly lower. However, the average time to achieve the
      maximum concentration and area under the curve over 24 h did not change.

PMID- 8160255
TI  - Diltiazem treatment impairs theophylline elimination in patients with
      bronchospastic airway disease.
AB  - On the basis of reports that diltiazem may bind to the hepatic microsomal enzymes
      and inhibits the metabolism of some co-administered drugs, and to determine the
      effects of diltiazem on theophylline pharmacokinetics in patients with
      bronchospastic airway disease, we have investigated the effect of a 180-mg daily
      dose of oral diltiazem during 5 days on theophylline clearance in eight patients
      with that disease. Theophylline half-life increased 24%, from 5.7 +/- 1 to 7.5 +/
      1.8 h (p < 0.05), and total body theophylline clearance showed a decrease of
      22%, from 87.3 +/- 20 to 68.3 +/- 18.6 ml/min (p < 0.05) after diltiazem therapy.
      The apparent volume of distribution was unchanged. This reduction in theophylline
      clearance is likely produced by inhibition of its metabolism by diltiazem. A
      clinically important drug interaction may occur with theophylline when diltiazem
      therapy is given concurrently in patients with bronchospastic airway disease.

PMID- 8160256
TI  - Effect of continuous hemofiltration on phenytoin elimination.
AB  - Phenytoin is frequently used to treat seizure episodes in critically ill
      patients. Some of these patients have acute renal failure, requiring continuous
      hemofiltration to help maintain fluid and solute balance. We evaluated the
      removal of phenytoin in patients who received the drug while undergoing
      continuous hemofiltration treatment. Arterial and ultrafiltrate sample pairs were
      collected for phenytoin concentration determination. The ultrafiltrate drug
      concentrations were almost identical to the free serum phenytoin concentrations.
      Thus the ultrafiltrate/arterial drug concentration ratios resembled the
      percentages of serum free drug. Between 0.32 and 0.78 mg of phenytoin/h was
      removed by hemofiltration. The magnitude of hemofiltration phenytoin removal was
      related to the free drug concentration, total serum drug concentration, and
      ultrafiltration flow rate. When the ultrafiltration flow rate was low, the amount
      of phenytoin removed by hemofiltration was small relative to the usual daily
      dose. However, in patients with renal failure in whom serum phenytoin protein
      binding is substantially reduced, continuous hemofiltration at a high
      ultrafiltration rate may remove a clinically significant amount of the drug.
      Higher daily doses of phenytoin may be needed to maintain the therapeutic effect.
      Serum drug concentration monitoring will be necessary to determine the optimal
      dosage regimen.

PMID- 8160257
TI  - Salivary theophylline monitoring: reassessment and clinical considerations.
AB  - To assess the reliability of salivary theophylline concentrations for patient
      monitoring, concentrations of theophylline in sera and saliva of 50 patients
      (ages 6-81 years) receiving oral or parenteral theophylline were determined by
      two methods: a rapid dry-phase apoenzyme reactivation system (ARIS) and
      fluorescence polarization immunoassay (FPIA). Saliva production was stimulated by
      both citric acid (CA) and parafilm (PF). With both analytical methods, there were
      excellent correlations between salivary theophylline concentration, CS, and
      unbound serum theophylline concentration CU (r2 > 0.95), and between CS and total
      serum theophylline concentration, CT (r2 > 0.85). CA- and PF-stimulated CS by
      FPIA resulted in concentrations within 2.0 micrograms/ml of the actual CU for
      100% of the samples measured (n = 47). By ARIS, 100% of the PF-stimulated CS and
      93.6% of the CA-stimulated CS determinations were within 2.0 micrograms/ml of the
      CU (n = 47). To evaluate the predictive capabilities of PF- and CA-stimulated
      saliva, one-half (n = 24) of the patients were randomly selected and their data
      used to predict the CT for the remaining patients. FPIA PF-CS predicted 83.3%
      (20/24) of CT within +/- 2 micrograms/ml, while ARIS CA-CS predicted 75.0% within
      +/- 2 micrograms/ml. There was no difference between FPIA CS and ARIS CS results
      by multivariate analysis of variance (MANOVA), but there was a difference between
      PF-CS and CA-CS (p < 0.05). However, when CU was used as a covariant, there was
      no significant difference. Using appropriate saliva collection procedures and the
      FPIA system, we conclude that CS provides adequate reliability for therapeutic
      drug monitoring of theophylline.

PMID- 8160258
TI  - A method for simultaneous measurement of cocaine and nicotine in neonatal hair.
AB  - Maternal exposure to drugs and chemicals is increasingly being recognized as
      adversely affecting the developing fetus. To date, a very large number of fetuses
      have been exposed in utero to cocaine and cigarette smoke. Neonatal hair as a
      biological marker for fetal exposure in cocaine and nicotine has emerged as an
      excellent tool in correlating in utero exposure and outcome. However, a limiting
      factor is the sparsity of neonatal hair. We report on the first method that
      allows determination of both cocaine and nicotine as well as their metabolites in
      the same hair samples.

PMID- 8160259
TI  - Monitoring of cyclosporine blood levels from central venous lines: a misleading
      assay?
AB  - In order to assess the suspected influence of indwelling lines on the measurement
      of cyclosporine (CSA) blood levels, we evaluated CSA concentrations in samples
      drawn simultaneously from both silicone catheter lumens and peripheral veins of
      eight bone marrow transplant recipients. Blood samples were obtained at 30 min or
      6-12 h after discontinuation of intravenous CSA. CSA concentrations were
      determined in whole blood by specific monoclonal antibody assay. Mean CSA levels
      from the lumen used for CSA administration were significantly higher than those
      from samples drawn from the second lumen (i.e., not used for CSA infusion) or
      peripheral vein. This difference, obtained when the infusion had been interrupted
      for 30 min, was still the case 6-12 h after discontinuation of CSA infusion. No
      difference was found between samples obtained from the second lumen and
      peripheral vein. These observations suggest that CSA might be adsorbed or bound
      by the silicon catheter and, thus, CSA blood level measurements may be
      misleading. The second lumen of the catheter or a peripheral vein should be used
      for accurate monitoring of CSA concentrations.

PMID- 8160260
TI  - Measurement of lamotrigine under conditions measuring phenobarbitone, phenytoin,
      and carbamazepine using reversed-phase high-performance liquid chromatography at
      dual wavelengths.
AB  - A reverse-phase high-performance liquid chromatographic (HPLC) method for the
      measurement of lamotrigine (LTG) simultaneously with phenobarbitone (PB),
      phenytoin (PHT), and carbamazepine (CBZ) is described using hexobarbital as the
      internal standard. The method uses the chromophore at 307 nm to detect LTG in the
      presence of interfering CBZ-10,11-epoxide detected at 220 nm, the wavelength used
      to measure the other drugs. This method requires < 10 min/sample for completion.
      Simultaneous monitoring of the chromatographs at 220 and 310 nm with a simple
      calculation allows LTG to be measured virtually identically to a routine method
      for monitoring of the other anticonvulsants. Between-batch precisions for LTG at
      2 and 6 mg/L were < 5%. Accuracy of LTG estimation was assessed by comparison
      with known values of samples supplied by an external quality assessment scheme.

PMID- 8160261
TI  - Simultaneous determination of felbamate and three metabolites in human plasma by
      high-performance liquid chromatography.
AB  - An isocratic liquid-chromatographic method employing one extraction step and a
      4.6 mm x 150 mm Spherisorb ODS2, 3 microns high-performance liquid chromatography
      (HPLC) column using ultraviolet (UV)-absorbance detection at 210 nm has been
      developed for quantitation of felbamate (FBM) and three felbamate metabolites in
      0.100-ml aliquots of human plasma. The linear quantitation range for FBM and the
      two hydroxy metabolites is 0.781-200 micrograms/ml, and that for the
      monocarbamate metabolite is 0.391-200 micrograms/ml.

PMID- 8160262
TI  - Simultaneous determination of felbamate, primidone, phenobarbital, carbamazepine,
      two carbamazepine metabolites, phenytoin, and one phenytoin metabolite in human
      plasma by high-performance liquid chromatography.
AB  - An isocratic liquid-chromatographic method employing one extraction step has been
      developed for the quantitation of five drugs and three metabolites in human
      plasma. The method uses 0.100-ml aliquots of human plasma and two internal
      standards. Chromatographic conditions include a 4.6 mm x 150 mm Spherisorb ODS2,
      3 microns a high-performance liquid chromatography, (HPLC) column, a phosphate
      buffer-acetonitrile-methanol (700:160:140) mobile phase, and ultraviolet (UV)
      absorbance detection at 210 nm. Analytes and linear quantitation ranges
      (microgram/ml) were felbamate (FBM) 0.391-200; primidone (PRIM), 0.098-100;
      phenobarbital (PHENO), 0.195-100; carbamazepine (CBZ), 0.195-100; phenytoin
      (PHT), 0.195-200. For CBZ-transdiol (CBZ-TR) CBZ-epoxide (CBZ-EP), and the PHT
      metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), the range was 0.049
      25.0 micrograms/ml. Ethosuximide, methsuximide, 2-methyl-2-phenyl-succinimide
      (methsuximide metabolite), 2-ethyl-2-phenyl malonamide (PRIM metabolite, 5-ethyl
      5-(4-hydroxyphenyl)-barbituric acid (PHENO metabolite), and mephenytoin do not
      interfere with quantitation of the above compounds.

PMID- 8160263
TI  - Springs and hinges: dynamic coiled coils and discontinuities.

PMID- 8160264
TI  - PH domains and phospholipases--a meaningful relationship?

PMID- 8160265
TI  - Phosphoinositides in vesicular traffic.

PMID- 8160266
TI  - Exploring molecular diversity with combinatorial shape libraries.
AB  - Surface technologies based upon selection of ligands from combinatorial libraries
      herald a revolution in molecular research and drug discovery. Molecular diversity
      is generated by random combinations of monomeric building blocks to form
      polymeric conformers that constitute 'shape libraries'. The media for exploring
      surfaces of target molecules include synthetic or biological polymers consisting
      of natural or modified amino acids, nucleotides, carbohydrates and other organic
      materials. Targets can be any biological surface, including enzymes, antibodies,
      receptors and other regulatory molecules. The power of combinatorial selection is
      in finding conceptual leads for designing high-affinity ligands and effector
      molecules for the analysis and manipulation of biochemical interactions.

PMID- 8160267
TI  - Functions of HIV envelope glycans.
AB  - The unusually highly glycosylated state of the major envelope glycoprotein
      (gp160) of the human immunodeficiency virus has offered a challenge to both
      glycobiologists and virologists. What is the functional significance of such a
      mass of glycans and how might they be manipulated to disadvantage virus
      pathogenesis? Some answers to each of these questions have already been obtained:
      N-linked glycans are necessary for the creation, but not the maintenance, of a
      bioactive conformation, and drug-induced alteration of the glycosylation pattern
      can lead to impaired virus infectivity. As a model for studying glycan function
      and as a target for antiviral therapy, gp160 represents a unique candidate.

PMID- 8160268
TI  - Two highly homologous putative DNA-binding proteins in yeast and E. coli.

PMID- 8160269
TI  - Protein kinase C--a question of specificity.
AB  - Following the initial identification of protein kinase C (PKC) by Nishizuka and
      co-workers in the late seventies, a wealth of information on this protein kinase
      has accumulated. Perhaps most striking was the realization that PKC is not just a
      single polypeptide but in fact consists of a large family of related proteins.
      These PKC isotypes are unique, not only with respect to primary structure, but
      also on the basis of expression patterns, subcellular localization, activation in
      vitro and responsiveness to extra-cellular signals. This review focuses on the
      heterogeneity within the PKC family and highlights some of the recent evidence
      that the isotypes might have separate and unique functions in the cell.

PMID- 8160270
TI  - Phosphoryl transfer in Flp recombination: a template for strand transfer
      mechanisms.
AB  - The basic chemistry involved in DNA recombination, RNA splicing and DNA
      transposition is a phosphoryl transfer reaction. This review is an attempt to
      provoke a unified thinking on the reaction mechanisms in these nucleic acid
      transactions. Some of the recent results with the Flp site-specific recombinase
      that reveal how the chemical reactivity for recombination is derived from
      cooperative protein-subunit interactions on the DNA substrate are discussed. At
      least some of the features of Flp reaction are likely to have global implications
      in other DNA and RNA strand-transfer systems.

PMID- 8160271
TI  - Xeroderma pigmentosum and nucleotide excision repair of DNA.
AB  - Nucleotide excision repair is a versatile strategy for removing DNA damage from
      the genome. Tremendous progress in understanding this process has been made in
      the last few years, and the field continues to develop rapidly. Exciting
      connections have emerged between nucleotide excision repair, transcription, and
      DNA replication, but many mysteries remain concerning the biochemical details of
      the mechanism, the connection with several human inherited syndromes, and the
      role of DNA repair in preventing cancer.

PMID- 8160272
TI  - Mitochondrial molecular chaperones: their role in protein translocation.
AB  - After synthesis in the cytosol, most mitochondrial proteins must traverse
      mitochondrial membranes to reach their functional location. During this process,
      proteins become unfolded and then refold to attain their native conformation
      after crossing the lipid bilayers. Mitochondrial molecular chaperones play an
      essential mechanistic role at various steps of this process. They facilitate
      presequence translocation, unfolding of the cytosol-localized domains of
      precursor proteins, movement across the mitochondrial membranes and, finally,
      folding of newly imported proteins within the matrix.

PMID- 8160273
TI  - Determining DNA concentrations and rescuing PCR primers.

PMID- 8160274
TI  - Ethics in pediatric research.

PMID- 8160275
TI  - The association between Henoch-Schonlein syndrome and renal amyloidosis: a
      proposal of a pathogenic mechanism.
AB  - The clinicopathological analysis of 250 pediatric cases that had been tissue
      diagnosed with renal amyloidosis revealed three patients associated with Henoch
      Schonlein syndrome (HSS). The renal biopsies revealed AA-type amyloidosis in all
      three cases. Case 2 displayed focal and segmental proliferative
      glomerulonephritis in the same renal biopsy. No evidence of well-known diseases
      and/or conditions for the development of AA-type amyloidosis except for familial
      Mediterranean fever (FMF) existed in these particular cases. On the other hand,
      the frequency of the association between FMF and HSS has been reported
      extensively in the literature; thus, common etiological factors can be
      considered. The mechanism involved in amyloid deposition in these cases may be
      related to HSS-associated chronic antigenemia and/or FMF through a mechanism that
      is, to date, unknown. Further studies are needed to clarify this causal
      relationship.

PMID- 8160276
TI  - The frequency of multiple births in central Anatolia.
AB  - The purposes of the present study were to contribute additional data regarding
      the frequency of multiple births in Ankara, and to reassess both the relation
      between maternal age and twinning, and the inter-relation between twinning and
      seasonality. The frequency of twinning was found to be 0.0084858 +/- 0.00028
      (0.85%), triplets 0.0001087 +/- 0.000031 (0.011%), and quadruplets 0.000009
      (0.0009%). It is observed that there is a correlation between the frequency of
      twinning, maternal age and parity, and that the rate of twinning increases with
      maternal age. The twinning rate varies according to the month of the year in
      which birth takes place. Accordingly, the frequency of twin births is greater
      between May and August, and lower between September and December.

PMID- 8160277
TI  - Is L-carnitine protective in hypoxic cerebral edema in newborn mice?
AB  - The value of carnitine in the prevention of cerebral edema due to acute severe
      hypoxia in 38 newborn mice was studied. Twenty-nine animals received normal
      saline (0.25 ml) or carnitine (16 mmol/kg) intraperitoneally, thirty minutes
      before exposure to 0% oxygen in inspired air for two minutes. Nine mice received
      no drug and were exposed to room air. After hypoxic insult, brain water content
      was measured and was found to be similar in all groups. These findings suggest
      that carnitine pretreatment does not prevent brain edema associated with cerebral
      hypoxia in newborn mice.

PMID- 8160278
TI  - Treatment of constitutional delayed puberty with a combination of testosterone
      esters.
AB  - Thirteen boys with constitutional delayed puberty (CDP) were treated with a
      combination of short and long-acting testosterone esters (testosterone
      propionate, testosterone phenylpropionate, testosterone isocaproate). Mean age at
      the onset of treatment was 14.9 +/- 0.6 years and bone age delay was -2.7 +/- 0.9
      years. The dose of testosterone used was 200 mg intramuscularly four times at
      three week intervals, and the treated CDP boys were followed for two years. All
      the boys with CDP entered puberty after the last dose (testicular volume > or = 4
      ml), and growth rate increased from 4.5 +/- 0.5 cm/year, pretreatment, to 8.4 +/-
      1.6 cm/year, posttreatment, at the two year follow-up. Height for bone age SD
      score did not change significantly from a mean of -1.1 before treatment to -1.3
      after treatment, nor did predicted height before treatment (173.5 +/- 6.6 cm) and
      after treatment (173.3 +/- 4.9 cm). Combination of testosterone esters in a given
      dose and schedule is a safe and effective treatment for prepubertal boys with
      constitutional delayed puberty.

PMID- 8160279
TI  - The use of IgM-enriched intravenous immunoglobulin for the treatment of neonatal
      sepsis in preterm infants.
AB  - The value of IgM-enriched immunoglobulin therapy in 44 preterm infants with
      neonatal sepsis was evaluated in a prospective randomized study. All infants
      received antibiotic therapy and fresh plasma and/or whole blood transfusions.
      Twenty randomly-chosen infants were allocated to receive 5 ml/kg/d of IgM
      enriched immunoglobulin intravenously for three days. Although the mortality rate
      in preterm infants whose gestational ages were 31-34 weeks in the immunotherapy
      group was slightly lower than in the control group, the general mortality rate
      from sepsis in the control group (9/24) and in the immunotherapy group (6/20)
      showed no statistically significant difference (37.5% vs 30.0%, p < 0.05).

PMID- 8160280
TI  - Moyamoya disease and alternating hemiplegia. A report of two cases.
AB  - Moyamoya disease is one of the cerebrovascular disorders and is characterized by
      bilateral stenosis or occlusion of the distal internal carotid arteries and their
      main branches. Repeated ischemic episodes in children and intracranial hemorrhage
      in adults with moyamoya disease is usually noted. In this report, we describe two
      children with moyamoya disease who presented with alternating hemiplegia. The
      final diagnosis was made by cerebral angiography and cranial computed tomography
      in these patients. Other neurological and radiological features of the patients
      were described.

PMID- 8160281
TI  - Computed tomography and angiographic findings of childhood moyamoya disease.
AB  - Moyamoya disease is a rare entity consisting of bilateral stenosis or occlusion
      of internal carotid arteries with abnormal collateral vessels at the base of the
      brain. We present five Turkish children with this disease, which is more common
      in Japan. Focal neurologic deficits and/or epilepsy were the common presenting
      symptoms in two girls and three boys between the ages of 1.5 and 11 years.
      Multiple cerebral infarcts were diagnosed in all of the cases by Computed
      Tomography (CT). Abnormal net-like vessels at the base of the brain were detected
      in three patients. Cerebral angiography, which is necessary to confirm the
      diagnosis, showed moyamoya vessels and bilateral stenosis or occlusion of the
      internal carotid arteries in all cases. Although the angiographic staging was
      advanced in three patients, neither clinical status nor parenchymal abnormalities
      detected with CT were different from the other two cases.

PMID- 8160282
TI  - Congenital cystic adenomatoid malformation. A report of a case and review of the
      literature.
AB  - A ten-month-old boy was admitted to our hospital with fever, cough and dyspnea.
      His history was remarkable for mild respiratory problems from the early neonatal
      period. Although medical treatment was administered several times in a local
      hospital, his symptoms recurred. Chest x-ray revealed multiple cystic lesions on
      the right side. The diagnosis of congenital cystic disease was considered
      preoperatively, to our knowledge for the first time in our hospital. The
      patient's postoperative course was uneventful, and no respiratory problems have
      recurred in 24 months of follow-up.

PMID- 8160283
TI  - The Aicardi syndrome. A case report and review of the literature.
AB  - A case of Aicardi's syndrome is described. The main features described are
      infantile spasms, pathognomonic chorioretinal lacunar defects, agenesis of the
      corpus callosum, psychomotor retardation, female sex, characteristic EEG changes
      and costovertebral anomalies. This is the second reported case in Turkey.

PMID- 8160284
TI  - The urological manifestations of the tethered spinal cord.
AB  - The tethered cord is the fixation of the cord resulting in stretching as growth
      occurs. In this paper, three cases of tethered cord with symptoms related to the
      urinary tract were presented. In the first case, a 12-year-old girl presenting
      with abdominal pain and urinary incontinence had bilateral hydronephrosis and
      neurogenic bladder due to a tethered cord without having any other
      neuropathological manifestation. In the second case, an eight-year-old girl
      presented with enuresis and a mass in her back was found to have a
      lipomyomeningocele, hyperactive tendon reflexes in the lower limbs and pes cavus.
      Tethered cord associated with lipomyomeningocele caused a neurogenic bladder and
      bilateral hydronephrosis. In the third case, a seven-month-old girl presented
      with hydrocephalus as well as bilateral dilation of the renal pelvis, unilateral
      ureteral duplication and vesicoureteral reflux. A tethered cord was revealed in
      this patient, who had a meningomyelocele operation in the neonatal period. Renal
      function test in the first two cases were abnormal.

PMID- 8160285
TI  - Leprechaunism (Donohue's syndrome): a case report.
AB  - Features of leprechaunism, including low-birth weight, a grotesque elfin face
      with clubbed nose, hirsutism, large low-set ears, enlarge external genitalia,
      distended abdomen with emaciated extremities, and growth and motor retardation
      were present in a 3-month-old girl. Because of parental consanguinity in this
      patient, a recessive mode of inheritance seems likely.

PMID- 8160286
TI  - The influence of pulmonary insufficiency on ventricular function following total
      correction of Fallot's tetralogy: evaluation using radionuclide ventriculography
      and clinical findings.
AB  - Long-standing pulmonary insufficiency after repair of tetralogy of Fallot may
      adversely affect ventricular function. We evaluated 20 patients postoperatively
      by radionuclide ventriculography and clinical findings after total correction of
      tetralogy of Fallot. Patients were divided into two groups as follows: Group I
      patients (10) had no pulmonary insufficiency; Group II patients (10) had moderate
      or severe pulmonary insufficiency. Preoperatively, there was no difference
      between groups in terms of age, functional capacity according to the New York
      Heart Association criteria, hemoglobin and hematocrit level, cardiothoracic
      ratio, McGoon ratio, left and right ventricular ejection fraction, cardiac output
      or cardiac index. Postoperatively, right ventricular ejection fraction was 40.10
      +/- 2.28 in Group I and 29.5 +/- 2.86 in Group II, p < 0.01. Left ventricular
      ejection fraction was 59.3 +/- 2.90 in Group I and 50.9 +/- 4.19 in Group II, p <
      0.01. Radionuclide ventriculography is a useful means of identifying right
      ventricular dysfunction following repair of tetralogy of Fallot. The dysfunction
      appears significantly worse in patients with pulmonary insufficiency.

PMID- 8160287
TI  - A case of Prader Willi syndrome with del 15 (q11-->q13).
AB  - Cytogenetic analysis was performed on a four-year-old girl with obesity, mental
      retardation, recurrent febrile convulsions and a provisional diagnosis of Prader
      Willi syndrome. High-resolution banding was done to observe the subchromosomal
      deletion. An interstitial deletion (q11-->q13) on one of the 15th chromosomes was
      observed in all metaphases.

PMID- 8160288
TI  - [Enzyme activity in rat intestines after exposure to x-irradiation].
AB  - It is established that 24 hours after total X-ray irradiation by doses of 0.5, 1
      and 2 Gy activity of intestine enzymes (saccharose and alpha-amylase) increases.
      A dose of 3 and above induces an increase of saccharose activity and inhibition
      of alpha-amylase. The functional state of basic phosphatase under action of the
      doses investigated remains practically unchanged.

PMID- 8160289
TI  - [Effect of radiation on the electrophoretic mobility of erythrocytes].
AB  - Electrons with energy 5 MeV have been studied for their effect on the
      electrokinetic properties of erythrocytes. The electrophoretic mobility of the
      cells was shown to decrease under the effect of radiation. It is supposed that
      the effect observed is determined by the structural changes of the membrane
      proteins.

PMID- 8160290
TI  - [Effect of liposomes on lipid peroxidation in the heart and liver in crush
      syndrome].
AB  - The increased lipid peroxidation has been determined to be one of general
      mechanisms of disturbance in the functional state of the heart and liver fraction
      cells, regularities of inter-system disturbance in metabolic activity under the
      crush syndrome have been revealed. Administration of lecithin liposomes results
      in the decreased POL levels, increased antioxidant capacity of the organism. That
      permits recommending to include liposomes into complex therapeutics of the crush
      syndrome as detoxicating, antiinflammatory and antihypoxic drug.

PMID- 8160291
TI  - [Effect of cadmium chloride on DNA-, RNA-polymerase activity and lipid
      peroxidation of chromatin fraction in rat liver].
AB  - Introduction of the cadmium chloride water solution to experimental animals
      induces changes in biochemical parameters which characterize structural and
      functional activity of transcriptionally active and repressed chromatin
      fractions. In the intoxicated chromatin-active fraction the DNA/protein ratio
      increases and DNA-polymerase alpha-activity decreases while in repressed
      chromatin activity of RNA polymerase I decreases as compared with controls.
      Change in intensity of lipoperoxidation reactions may underlie the cadmium
      chloride genotoxicity. This thesis is proved by an augmented level of NADPH
      induced lipoperoxidation in active chromatin fraction.

PMID- 8160292
TI  - [Properties of polyreactive immunoglobulins].
AB  - Some biological properties of polyreactive antibodies (PRABs) from the serum of
      mice, rabbit and cattle are investigated. Optimal parameters of the activation
      process are determined. It is shown that solution of KSCN (potassium rhodanide)
      more effectively impedes interaction of PRABs with the antigen on the
      immunological plate than interaction between specific antibodies. Dynamics of
      binding of PRABs and affine-purified antibodies to an immobilized antigen is
      analyzed. The competitive ELISA shows the absence of specificity of PRABs and
      their less avidity in comparison with the usual antibodies. It is supposed that
      PRABs play an essential role in the immune system of animals and man.

PMID- 8160293
TI  - [Effect of various specific agents on the heat stability of human serum albumin].
AB  - Effect of lipoic acid, 5,5-dithiobis-2-nitrobenzoic acid, monoiodoacetic acid and
      cystine on thermal stability of human serum albumin was studied by differential
      scanning calorimetry and electrophoretic methods. Quantitative estimation of the
      protective effect of these reagents on resistance of 5% solutions of albumin to
      the temperature influence was studied. It is concluded that all the compounds
      used protect albumin from polymerization at heating.

PMID- 8160295
TI  - [Characterization of the nuclease-sensitive chromatin regions from N
      nitrosodiethylamine-induced hepatoma cells].
AB  - Protein-DNA complexes released from chromatin of the intact rat liver and
      hepatoma induced by N-diethylnitrosamine during nuclease digestion have been
      subdivided into two groups of high and low molecular weight. Immunoreactive
      proteins are concentrated mainly in high molecular complexes. Immunoblotting of
      proteins from the nuclease-sensitive regions of normal and tumor chromatins allow
      distinguishing antigens of three main types: 1--antigens of nuclease-sensitive
      samples common both for normal and tumor cells; 2--antigens determined in tumor
      preparations only; 3--antigens usual for normal samples. Such differences in
      composition of immunogenic proteins in the nuclease-sensitive regions from the
      cells of the normal and malignant rat liver may be useful for investigating
      changes in active chromatin during chemical induction of tumors in animals.

PMID- 8160294
TI  - Investigation of low ionic strength effect on passive monovalent cation transport
      through erythrocyte membranes.
AB  - Effect of low ionic force on the passive transport of univalent cations through
      the erythrocyte membranes is considered. It is postulated that this effect is
      complex and cannot be explained on the basis of electrodiffusion. Data are
      presented on the already known transport pathways in the erythrocyte membranes
      for univalent cations. Characteristics of residual cation transport (the "leak"
      flux) through the erythrocyte membranes also affected by the low ionic force are
      presented.

PMID- 8160296
TI  - Similarity of the effects of tosyl-L-arginine methyl ester, atropine, caffeine
      and antitumour alkylating agent on some biological functions of thrombin and
      platelet 12-lipoxygenase.
AB  - The effect of the synthetic thrombin substrate (TAME) and three compounds
      exerting an opposite effect on Ca-PPI and AdC (caffeine, atropine and meta-tolyl
      derivative of mechlorethamine (TDM)) on hormone-like and catalytic functions of
      thrombin was studied. It is shown that both TAME and other drugs under test block
      effectively the thrombin-induced platelet aggregation, as well as protect the
      active site of the enzyme from denaturation by dithiothreitol. The same compounds
      inhibit thrombin in thrombin-fibrinogen reaction and platelet 12-lipoxygenase.
      These data suggest identity of thrombin moieties which determine its enzymatic
      and hormone-like activities.

PMID- 8160297
TI  - [Activity of proteinases and alpha-1-proteinase inhibitor under cold stress in
      rats].
AB  - Proteinase and alpha-1-proteinase inhibitor (alpha-1-PI) activity has been
      investigated in the dynamic of the cold influence in rats. A rise of proteinase
      activity against a compensatory drop of alpha-1-PI level two hours later their
      action was observed. Proteolysis activation stimulated the alpha-1-PI synthesis
      or its release in the blood circulation. A new wave of proteolysis occurs in
      response to the alpha-1-PI increase. This tight correlation between proteinase
      and alpha-1-PI activity changes testifies that reactions of organic proteolysis
      are very significant in the stress response stimulation under the cold influence.

PMID- 8160298
TI  - [Use of conductometric microsensors for studying kinetic parameters of enzymes].
AB  - An alternative method based on thin-film conductometric microsensor is suggested
      for studying enzyme kinetics. It is established that the immobilized enzyme as
      well as soluble one is described by the classic lows of enzyme kinetics. Major
      parameters (Km and Vmax) are identical to those measured by the widely used
      methods and their amounts are 1.33 mM and 9.04 microS/min for soluble urease and
      3.73 mM and 13.8 microS/min for immobilized urease; 5.26 mM and 13.9 microS/min
      for immobilized glucose oxidase; 13.6 mM and 122.0 microS/min for immobilized
      acetyl cholinesterase; 10.8 mM and 129.9 microS/min for immobilized butyryl
      cholinesterase. The possibility of conductometric analyzer application for
      detection of toxin concentration, in particular pesticides, is shown. Advantages
      and disadvantages of the system suggested are discussed.

PMID- 8160299
TI  - [Aldehyde dehydrogenase activity of blood serum exposed to different
      concentrations of acetaldehyde].
AB  - Aldehyde-dehydrogenase activity of blood serum of practically healthy people,
      patients with chronic alcoholism (stage II) and in the experiment with intact
      animals (white rats) were studied in comparative aspect. Optimal conditions have
      been chosen to reveal aldehyde-dehydrogenase activity. It has been shown that
      aldehyde dehydrogenase of blood serum in healthy people manifests activity at
      very low (0.012 mM; aldehyde dehydrogenase 1), low (0.060 mM; aldehyde
      dehydrogenase 2) and high (1 mM; aldehyde dehydrogenase 3) concentrations of
      acetaldehyde. Activity of aldehyde dehydrogenase 1 is not revealed in patients
      with chronic alcoholism, while the values of activity of aldehyde dehydrogenase 2
      and aldehyde dehydrogenase 3 are decreased. Aldehyde dehydrogenase 2 and aldehyde
      dehydrogenase 3 have been revealed in the rat blood serum. The apparent values Km
      and V have been calculated for aldehyde dehydrogenase 1 in people and aldehyde
      dehydrogenase 2 in rats when using acetaldehyde and NAD as the reaction
      substrates.

PMID- 8160300
TI  - [Norepinephrine content in various brain structures and activity of alcohol
      dehydrogenase and aldehyde dehydrogenase in blood serum of rats with varying
      predisposition to ethanol consumption].
AB  - Noradrenaline content in hypothalamus, midbrain and new cortex as well as the
      activity of alcohol- and aldehyde dehydrogenase in the blood serum of rats with
      different alcohol motivation were studied. It is shown that rats, which prefer
      ethanol, are characterized by the lower content of noradrenaline in hypothalamus,
      midbrain and new cortex as compared to animals which prefer water. It is found
      out that alcohol motivation in rats correlates with high activity of blood serum
      aldehyde dehydrogenase. No reliable relation between ethanol preferring and
      activity of blood alcohol dehydrogenase was revealed.

PMID- 8160301
TI  - [Effect of pyridoxal phosphate on the activity of aminotransferases in different
      structure-functional regions of the rabbit brain in radiation sickness].
AB  - Pyridoxal enzymes of transamination (aspartate aminotransferase, KF 2.6.1.1. and
      alanine aminotransferase, KF 2.6.1.2) have been studied for their activity in
      different departments of the rabbit brain under the effect of ionizing radiation
      and introduction of pyridoxal phosphate. It has been established that the effect
      of ionizing radiations does not evoke the change in aspartate aminotransferase
      and alanine aminotransferase activity in different structure-functional
      departments of the rabbit brain, the decrease of aminotransferases activity in
      the acute period of the radiation sickness being natural. Introduction of
      pyridoxal phosphate irradiated animals promotes relative normalization of
      activity of the enzymes under study.

PMID- 8160303
TI  - [Modulation of intracellular pools of cyclic purine nucleotides by biologically
      active oxysterol-ecdysterone and vitamin D3].
AB  - The dynamics of changes in the level of cyclic purine nucleotides was studied in
      the tissues of rats with experimental D-hypovitaminosis in the range of 5 min-24
      h after administration of hormonal doses of polyhydroxylated ecdysterone
      hydroxysterolne and predecessor of 1.25-dihydroxycholecalciferol (calcitriol)-
      vitamin D3. The early sharp increase of intracellular pools cEMP in the liver
      tissue, small intestine, brain and heart mucosa was observed. It precedes the
      modulation of nucleic acid biosynthesis and supposes activation of the effect of
      oxysterenes of G-signal (phospholipid) system in the early phase at the expense
      of interaction with receptors exposed on plasmatic membrane of the cells.

PMID- 8160302
TI  - [Interaction of immobilized lectin from Leucojum vernum L. with polysaccharides
      and glycoproteins].
AB  - Interaction of D-mannose-specific lectin from Leucojum vernum L. with
      polysaccharides and glycoproteins has been studied on the column of immobilized
      lectin and by precipitation. Lectin is found to precipitate human and bovine
      thyroglobulin, yeast mannan, mannofucogalactans from Aphyllophores mushrooms and
      rystomycin sulfate. Lectin does not interact with yeast glycogen and gel sephadex
      and this differentiates it from Leucojum vernum L., Concanavalin A and pea
      lectin. All glycoconjugates are divided into three groups: those which are not
      bound with immobilized lectin; partly bound with Leucojum vernum lectin and
      completely bound with the column. Glycoconjugates that are partly bound with
      immobilized lectin are, probably, glycosyl moiety. The obtained results are
      discussed.

PMID- 8160304
TI  - [Mechanism of action of ecdysterone in chickens with D-hypovitaminosis. Early
      phase of effect].
AB  - Early action of ecdysterone in enterocytes of thin intestine of chickens with
      experimental D-hypovitaminosis has been studied with the aim to find out
      molecular mechanisms of its action. Changes in biosynthesis of nucleic acids
      accompanied with normalization of Ca translocation, biosynthesis of proteins,
      lipids and nucleic acid precursors (purine and pyrimidine nucleotides) as well as
      oxypurines were observed over the time interval (0-2 h) after ecdysterone
      administration. Multifunction character of the early action of ecdysterone
      indicates to the intermediary mechanism of gene activation by ecdysterone and
      provides for the availability of the secondary mediator for realization of its
      biological action in enterocytes.

PMID- 8160305
TI  - [Transport of 2,5-dimethoxy-4-methylamphetamine by macroheterocycles across
      erythrocyte membranes].
AB  - Transport of 2,5-dimethoxy-4-methylamphetamine across human erythrocytes by the
      18-crown-6, monoaza-15-crown-5 and diaza-18-crown-6 is studied and evaluated
      spectrophotometrically. It is shown that crown-ethers at low concentration (1-2
      mM) protect erythrocytes against their natural homolysis. 2,5-dimethoxy-4
      methylamphetamine provides 2-5% hemolysis of erythrocytes. In the presence of
      macrocycles (5 mM) hemolysis of erythrocytes increases from 6.5 to 30%. A
      hemolytic effect of 2,5-dimethoxy-4-methylamphetamine depends on the structure of
      the crown ethers and, apparently, confirms significant role of complexes of the
      crown-ethers with amine in these processes.

PMID- 8160306
TI  - [Acetylcholine and effectiveness of oxidative phosphorylation in isolated rat
      hepatocytes].
AB  - It is shown that ADP and DNP does not intensify the respiration rate in
      hepatocytes of rats obtained by means of trypsin or EDTA. The same cells obtained
      using collagenase, phosphorylate added ADP and increase the respiration rate
      after DNP addition. Acetylcholine added to the cell suspension in a dose of 5 x 4
      x 10(-8) M) increases the efficiency of oxidative phosphorylation. The scheme of
      neurotransmitter regulation of intensity of respiration and efficiency of
      oxidative phosphorylation on the cell level is suggested.

PMID- 8160307
TI  - High-density morphologies of ice in high-pressure frozen biological specimens.
AB  - Mouse liver tissue was rapidly cooled by high-pressure freezing at a nominal
      pressure of 2100 bar. Ultrathin cryosections were examined at 110 K with a
      cryoelectron microscope and the state of water was studied on micrographs and
      electron diffraction patterns. The results are compared with those from liver
      specimens cryofixed at ambient pressure by plunge freezing. The high-pressure
      frozen specimens contained crystalline frozen regions as well as areas which were
      vitreous. The spot diffraction patterns from crystalline regions are found to
      differ from those known for hexagonal ice. The comparison with powder diffraction
      data reveals the presence of the high-density morphologies Ice II and Ice III.
      Vitreous areas of biological samples frozen at ambient pressure are optically
      denser than areas where the water crystallised as cubic or hexagonal ice.
      However, on micrographs from high-pressure frozen samples, no significant
      contrast is found. This observation is explained by the higher specific mass of
      high-pressure ice compared to Ice I, an interpretation which requires a higher
      specific mass for high-pressure vitreous water compared to vitreous water
      produced at ambient pressure. The larger diffuse first ring of the diffraction
      pattern from high-pressure vitreous water confirms this argument.

PMID- 8160308
TI  - The ribosome at improved resolution: new techniques for merging and orientation
      refinement in 3D cryo-electron microscopy of biological particles.
AB  - Cryo-electron microscopy of single biological particles opens up new
      possibilities for structure analysis: the particle can be reconstructed in its
      native shape and internal features are preserved. To take advantage of these
      possibilities we have developed new methods of data collection and image
      processing and we have applied them to the 70S Escherichia coli ribosome. A
      method of orientation search is proposed, which makes it possible to relate
      random-conical data sets to one another even if they are collected from low-tilt
      micrographs. A technique for 3D alignment of projections is described and applied
      to the single-micrograph 3D reconstruction.

PMID- 8160309
TI  - [The diagnosis and treatment of hypospadias in girls].
AB  - The author recognizes 3 forms of hypospadia in girls: vestibular (partial),
      vestibulovaginal (subtotal) and vaginal (total). Clinical characteristics of
      these forms are provided. An original surgical aid in vaginal (total) hypospadia
      in girls is described.

PMID- 8160310
TI  - [Gunshot wounds of the bladder and urethra].
AB  - The analysis of medical aid rendered to 48 patients with bladder and 31 with
      urethral wounds showed that virtually all the wounds were combined. This fact
      aggravates the prognosis, presents difficulties for diagnosis and treatment. The
      authors state that x-ray examinations (cystography and urethrography) are rarely
      used in the diagnosis of the above injuries (in 8.3 and 16% of cases,
      respectively) in spite of their usefulness. It is emphasized that negligent
      attitude of the surgeon to epicystostomy and drainage of the pelvic fat may
      entail very serious complications.

PMID- 8160311
TI  - [The characteristics of the treatment procedure in acute suppurative
      pyelonephritis in diabetic patients].
AB  - From 1986 to 1992 the authors treated 160 patients with acute purulent
      pyelonephritis (APP) associated with diabetes mellitus (DM). 100 patients were
      diagnosed to have diffuse-purulent pyelonephritis (DPP), 60 patients (37.5%) had
      purulent-destructive pyelonephritis (PDP). The authors carried on two different
      surgical policies: in 1986-1988 a conservative approach was followed (7 out of 21
      patients underwent nephrectomy, 14 underwent nephrostomy and other organ-sparing
      operations), in 1989-1992 a radical approach was used. After the nephrostomy
      there were 7 lethal outcomes (53.8%) and 6 cures. Histological examination of the
      kidneys from the latter patients revealed DPP with major renal pelvic
      involvement. Lethal outcomes were caused by intoxication resultant from
      progressive purulent destruction in the operated on kidney in the presence of
      uncorrectable hyperglycemia with ketoacidosis. In view of mutual aggravation
      observed in APP and DM and ineffectiveness of nephrostomy in PDP, indications to
      radical removal of the inflammation focus (nephrectomy) are of vital character.
      This explains why the conservative approach was changed for the radical one
      according to which nephrectomy was conducted in 37 (94.8%) of the surgical
      patients. Lethal outcomes of nephrectomy under the radical approach reached 27%.
      The employment of active radical policy reduced postoperative lethality by 26.8%.
      It is inferred that in DPP conservative methods including nephrostomy are valid.
      IN PDP primary nephrectomy in justified. Overall positive results were achieved
      in 80% of the patients. A 20% lethality was due to severe DM, APP form and
      imperfect therapeutic policy.

PMID- 8160313
TI  - [The epidemiology of the most prevalent kidney diseases in the nationalities of
      the North].
AB  - Health examination of events in the Evenki Autonomic Region and events in Yakutia
      using multiprofile questionnaires revealed high incidence of renal diseases:
      chronic pyelonephritis, chronic cystitis, nephroptosis. The former occurs most
      frequently, runs in association with nephroptosis and chronic cystitis, affects
      females more frequently than males. Nephroptosis is attributed to a nomad's life
      which the natives lead. In spite of high urinary oxalates and urates levels,
      urolithiasis in the Northerners occurs relatively seldom.

PMID- 8160312
TI  - [The physicochemical and biochemical signs of nephrolithiasis].
AB  - Urolithiasis diagnosis by uroliths presence reflects insufficient knowledge of
      the disease pathogenesis. 42 patients with oxalocalcium nephrolithiasis and 20
      healthy patients were examined for differences in the urine and plasma
      composition. The authors studied factors involved in regulation of mineral
      metabolism and urinary elimination of crystal-forming substances. The patients
      with urinary stones compared to the control are characterized by low total
      crystal-inhibiting activity, hyperosmia, hypodipsia, decreased surface free
      energy, high quantities of ionized calcium, low ionized magnesium in the urine,
      oligo- and uricosuria. Shifts in hormonal regulation in nephrolithiasis result
      from slight elevation of urinary cyclic adenosine monophosphate, a relative rise
      in the levels of aldosterone and parathyroid hormone, low blood calcitonin, all
      the changes being statistically significant.

PMID- 8160314
TI  - [The advisability of performing excretory urography in renal colic].
AB  - Basing on their experience with 1115 cases of prehospitalization excretory
      urography, the authors think it misleading to reject excretory urography at the
      height of renal colic because normal kidney completely excretes contrast medium.
      It is shown that a part of the latter is deposited by the affected kidney and
      fills the upper urinary tracts up to the level of the obstacle causing acute
      urostasis. Excretory urography at the height of renal colic is valid in hospitals
      with 24-hour x-ray service and in cases of urgent surgery.

PMID- 8160315
TI  - [The effect of remote-controlled shock-wave lithotripsy on kidney function].
AB  - Leucine arylamidase (LAA) excretion in circadian urine of 79 patients suffering
      from nephroureterolithiasis was measured before and after the session of remote
      impulse lithotripsy (RIL) to investigate the effect of the impulse on renal
      function. The stones were localized in the calyces, pelvis and upper third of the
      ureter. The patients were divided into 2 groups: 43 patients with noncomplicated
      nephroureterolithiasis (group 1) and 36 patients with complicated one including
      12 subjects exposed to the second RIL (group 2). The enzyme excretion was
      significantly reduced in group 1 patients. Its activity recovered in group 1
      within 6-7 days, in group 2 for 10-14 days. After the second RIL procedure LAA
      activity in the urine enhanced more rapidly, especially in group 2 patients. In
      calyceal, intrarenal pelvic and fused kidney location of the stone, LAA activity
      got more elevated than in the extrarenal pelvis or in the upper third of the
      ureter. It is demonstrated that RIL exhibits a short-term effect on the kidneys
      which depends on the presence of inflammation, the number of sessions, stones
      location and the number of impulses.

PMID- 8160316
TI  - [Preserved xenografts for the experimental replacement of bladder wall defects].
AB  - In 3 series of experiments on 62 rabbits the author tested feasibility of plastic
      correction of vast defects in the urinary bladder wall with human dura mater and
      pericardium pretreated with various proteolytic enzymes (papain, trypsin,
      chymotrypsin) of animal and plant origin. The levels of total protein were
      measured in the course of enzymatic proteolysis according to Lowry technique. The
      xenografts were studied biochemically prior to the proteolysis and after the
      treatment with proteolytic enzymes 6 times once an hour. The evidence was
      verified morphologically. Micromorphologically, the surface of the bladder was
      completely covered with connective tissue, the epithelium overgrew into some part
      of the transplant from the mucosa. Lecozyme was more effective in the
      pericardium, trypsin--in the dura mater. It is stated biochemically that optimal
      incubation time for proteolytic treatment of the xenograft is 3 hours.

PMID- 8160317
TI  - [The results of the diversion of urine into a large-intestine reservoir].
AB  - Cystectomy for bladder cancer with derivation of the urine into the colon was
      performed in 35 patients (30 males and 5 females). Postoperative lethality was
      11.4% (4 patients). The best outcomes in cases of partial and/or complete failure
      of the ileocecal valve were obtained when forming the invaginate in the stomal
      ileum. Examination following the surgery was conducted in 31 patients. Of them,
      preoperative passage from the upper urinary tracts was impaired in 22 (71%)
      because of the tumor spread into the ostium urethritis. Postoperative defect from
      the upper urinary tracts was recorded in 7 (22.6%) patients, while normal
      function of the kidney was registered in 24 out of 31 patients (77.4%). A
      complete retention of the urine was achieved in 27 of 31 patients (87.1%). With
      time, the capacity of the colon reservoir increased up to 750 +/- 57.9 ml to the
      end of the second postoperative year. The right part of the colon, cecum or
      ascending colon as well as the proximal third of the transverse colon as the
      reservoir served satisfactorily.

PMID- 8160318
TI  - [Radioisotope renography in the assessment of kidney function and urodynamics in
      children following the surgical treatment of hydronephrosis].
AB  - The paper provides radionuclide findings in children surgically treated for
      hydronephrosis. Altogether 109 children were operated on according to the
      technique by Andersen-Hines-Kucher with ureteral intubation and pelvic drainage.
      The radionuclide investigation allows determination of the time needed for
      functional recovery of the operated on kidney as well as visualization of changes
      in the contralateral follow-up period. Preoperative age-related changes in
      recovery of secretory and excretory functions of the operated on kidney were
      investigated.

PMID- 8160319
TI  - [A new approach in the surgery of prostatic sclerosis].
AB  - The authors propose a new technique of prostatic sclerosis surgery which makes
      use of a transperineal approach and is based on the principles underlying
      surgical management of posterior urethra high strictures with establishment of a
      cystourethral shunt. Good results obtained in 17 patients with prostatic
      sclerosis allow the authors to consider the above procedure as an alternative to
      transvesicular prostatectomy according to V. S. Karpenko.

PMID- 8160320
TI  - [Testicular prosthesis after subcapsular orchiectomy].
AB  - A technique of plastic testicular reconstruction from scrotal tissue after
      subcapsular orchiectomy has been developed. The procedure involves formation of a
      gauntlet graft from scrotal tissue which is implanted into tunica albuginea
      cavity after removal of testicular parenchyma. The graft is fixed in the cavity
      and the cut is sutured up to the graft pedicle. The grafts sized 5 x 4 x 3 cm-5.5
      x 4.5 x 4.0 cm were established in 14 patients. Postoperative 4-year follow-up
      registered neither complications nor graft size diminution.

PMID- 8160321
TI  - [Vitamin K1 and C excretion by the kidneys in chronic kidney failure].

PMID- 8160322
TI  - [The clinical efficacy of plasmapheresis in the combined therapy of patients with
      chronic glomerulonephritis and nephrotic syndrome].
AB  - A clinical analysis of the effect of 64 plasmapheresis sessions in combined
      treatment of 16 chronic glomerulonephritis patients with nephrotic syndrome was
      made for 7 patients with mesangiocapillary, 1 with mesangioproliferative, 2 with
      mesangioproliferative with semilunums, 2 with fibroplastic glomerulonephritis. 12
      of the patients had failed previous chemotherapy with prednisolone, curantil,
      cyclophosphamide. Each of the patients underwent 3-5 sessions of plasmapheresis.
      The domestic-made centrifuge pi phi-05 was employed. Plasmapheresis was combined
      with prednisolone (1.5 mg/kg/day) as early as session 1 in 6 patients, session 3
      in 10 patients (pulse therapy with 1 mg). Plasmapheresis was followed by curantil
      and chlorbutin administration. The results evaluated 2 months after the treatment
      start showed that renal function became normal in 4 patients, proteinuria
      diminished by 50-80% in 9 cases, nephrotic syndrome transformed into the urinary
      one in 5 patients.

PMID- 8160323
TI  - [The morphofunctional instability of the lymphocyte membrane in patients with
      chronic kidney failure].
AB  - T-lymphocyte E-receptor activity, mobility of the surface and deep parts of
      lymphocytic membrane lipid bilayer and membrane transport function were studied
      in 47 patients with chronic renal failure (16 had a conservatively curable and 31
      terminal stages). A rosette test, polarization of the fluorescent probes I
      anilino-naphthaleno-8-sulfonate and pyrene, inclusion of 14C-uridine into
      immunocompetent cells were employed, respectively. The investigations demonstrate
      morphofunctional instability of the lymphocytic membranes as indicated by shifts
      in RFC E-receptor activity, in reduced microviscosity of the lipid bilayer and
      transport dysfunction. The disturbances progress with deterioration of renal
      function with their peak at the terminal stage of the disease. It is suggested
      that morphofunctional damage to the lymphocyte membranes cause, among other
      factors, lymphocytopenia and secondary immunodeficiency in chronic renal failure.

PMID- 8160324
TI  - [Fracture of the penis].

PMID- 8160325
TI  - [Pheochromocytoma of the bladder].

PMID- 8160326
TI  - [The course of osteodystrophy in patients with chronic kidney failure on
      hemodialysis].

PMID- 8160327
TI  - [Corrective operations in ureterocele in children].
AB  - The authors analyze their experience in the treatment of 59 children aged 3
      months--14 years with ureterocele of the single (22 patients) and double ureter
      (37 patients). Examination and surgical data showed that ureterocele in the
      operated on children was congenital and became a component of a complicated
      malformation of the distal ureter. Structural changes varied from minimal to
      total dysplasia reflected in the degree of the ureteral dilatation. These changes
      were characteristic for both normal and double ureters and served the base for
      treatment policy decision. In normal megaureter the authors performed resection
      of the distal ureter as well as ureterocele, modelling and neoplantation of the
      proximal segment according to the antireflux technique. Minor dilatation of the
      pelvic ureter (up to 1.0-1.5 cm dependent on the patient's age) indicated that
      structural alterations of its wall are confined to the submucosal segment. In
      view of this, surgical intervention involved only endovesicular
      electroperforation of ureterocele. The policy in the double ureter ureterocele
      was based on the same criteria.

PMID- 8160328
TI  - Duration of protective efficacy of equine influenza immunostimulating
      complex/tetanus vaccines.
AB  - Seven previously untreated five-month-old New Forest ponies received two doses of
      equine influenza immunostimulating complex vaccines, one with and one without an
      immunopurified tetanus toxoid component, given by deep intramuscular injection
      six weeks apart, followed by a booster dose without tetanus toxoid five months
      later. Fifteen months after the third dose of vaccine, the ponies were challenged
      by exposure to an aerosol of influenza A/Equine 2/Sussex/89 (H3N8), a virus
      isolated from a recent outbreak of influenza A/equine 2 in Britain. The challenge
      produced severe clinical signs of influenza (pyrexia and coughing) in five
      unvaccinated control ponies. Four of the vaccinated ponies were completely
      protected against clinical disease, and two of these were also protected against
      infection as demonstrated by their lack of an antibody response after challenge.
      No coughing was recorded among the vaccinated ponies, and only three of the seven
      vaccinated ponies experienced a transient mild pyrexia. The mean duration and
      severity of the pyrexia among the vaccinated ponies was significantly less (P <
      0.01) than among the controls, and the excretion of virus was almost eliminated,
      thus demonstrating the protective efficacy of the vaccines 15 months after
      vaccination. Monitoring of tetanus antitoxin antibodies showed that protective
      levels (> or = 0.01/iu/ml) were maintained for at least 20 months after
      vaccination.

PMID- 8160329
TI  - Lameness in dairy cows and farmers' knowledge, training and awareness.
AB  - Lameness in dairy cattle is important from welfare and economic points of view.
      In 15 dairy farms in England, the prevalence of lameness was correlated highly
      significantly and inversely with the knowledge, level of training and awareness
      of the farmers.

PMID- 8160330
TI  - An outbreak of tuberculosis in a captive herd of Arabian oryx (Oryx leucoryx):
      management.
AB  - An outbreak of tuberculosis due to Mycobacterium bovis in a herd of Arabian oryx
      (Oryx leucoryx) was managed by sanitary and medical measures. The sanitary
      measures included the isolation of infected animals, the monitoring of animals
      with a range of diagnostic tests and the hand-rearing of the progeny of the
      infected herd. All the infected oryx were treated with a mixture of isoniazid at
      10 mg/kg bodyweight, ethambutol hydrochloride at 15 mg/kg bodyweight and
      rifampicin at 10 mg/kg bodyweight administered daily in the drinking water. These
      measures resulted in the cessation of mortalities, a decrease in the numbers of
      moderate and high risk animals and the production of tuberculosis-free animals
      for reintroduction into the wild.

PMID- 8160331
TI  - Spongiform encephalopathy in a greater kudu (Tragelaphus strepsiceros) introduced
      into an affected group.

PMID- 8160332
TI  - Ovarian and clinical response of cattle to buserelin.

PMID- 8160333
TI  - Production of antibodies to biosynthetic human growth hormone in the dog.

PMID- 8160334
TI  - Excretion of Cryptosporidium parvum oocysts by a herd of beef suckler cows.

PMID- 8160335
TI  - Postgraduate qualifications in animal welfare.

PMID- 8160336
TI  - Postgraduate qualifications in animal welfare.

PMID- 8160337
TI  - Postgraduate qualifications in animal welfare.

PMID- 8160338
TI  - Availability of poultry vaccines.

PMID- 8160339
TI  - Suspected vertical transmission of BSE.

PMID- 8160340
TI  - Feline dysautonomia in group-housed cats.

PMID- 8160341
TI  - Bovine multiple births.

PMID- 8160342
TI  - FeLV incidence.

PMID- 8160343
TI  - Pregnancy diagnosis by ultrasound.

PMID- 8160344
TI  - Pregnancy diagnosis by ultrasound.

PMID- 8160345
TI  - Avian heterophils and monocytes: phagocytic and bactericidal activities against
      Salmonella enteritidis.
AB  - The ability of heterophils and monocytes from domestic chickens and turkeys to
      phagocytize and kill Salmonella enteritidis (SE) was investigated using both a
      standard plate count (chickens only) and direct microscopic examination by
      staining with acridine orange (both chickens and turkeys). Optimal phagocytosis
      of SE by both chicken and turkey phagocytes required opsonization of the bacteria
      by antibodies as determined by both assays. However, heterophils from both the
      turkeys and chickens phagocytized more SE than did monocytes from either type of
      fowl. Regardless of the presence or absence of antibodies, heterophils were more
      efficient bactericidal cells than were the monocytes since only heterophils
      killed the intracellular bacteria while the majority of nonopsonized SE survived
      in the monocytes. Phagocytosis of SE did not result in an increase in the amount
      of superoxide anion released by the heterophils suggesting that the ultimate fate
      of the bacteria in these cells was not related to an oxygen-dependent mechanism.

PMID- 8160346
TI  - Periplasmic location of Brucella abortus Cu/Zn superoxide dismutase.
AB  - Two types of superoxide dismutase (SOD) have been found in Brucella abortus, a
      cytosolic Mn-SOD and a Cu/Zn-SOD of unknown location. We sought to determine the
      subcellular location of Cu/Zn-SOD in B. abortus ST 19. We report a modified
      spheroplasting procedure for the release of periplasmic contents from B. abortus
      cells using a dipolar ionic detergent, Zwittergent 316. This detergent, used in
      place of EDTA, destabilizes the outer membrane sufficiently to allow penetration
      of lysozyme and the subsequent selective release of periplasmic proteins by
      osmotic shock. Cytoplasmic cross-contamination of periplasmic fractions was
      assessed by assaying for malate dehydrogenase activity. Cyanide-sensitive and
      cyanide-insensitive SOD activity was measured by both the xanthine oxidase
      cytochrome c method and a hematoxylin assay. Results suggest that B. abortus
      Cu/Zn-SOD activity is periplasmic. This zwittergent-lysozyme extraction procedure
      may be applicable to the separation, isolation and characterization of many other
      periplasmic proteins of B. abortus and other Gram-negative organisms especially
      when cytosolic contamination is undesirable.

PMID- 8160347
TI  - Evaluation of long chain lipopolysaccharides (LC-LPS) of Actinobacillus
      pleuropneumoniae serotype 5 for the serodiagnosis of swine pleuropneumonia.
AB  - Long chain lipopolysaccharides (LC-LPS) of Actinobacillus pleuropneumoniae
      serotype 5 have been evaluated and compared with a crude boiled extract (CBE) in
      ELISA for the serodiagnosis of swine pleuropneumonia caused by this serotype. The
      mean optical density (OD) obtained with the LC-LPS in ELISA using sera from
      negative herds as well as from animals experimentally and naturally exposed to A.
      pleuropneumoniae serotype 5 was not significantly different from that obtained
      with the CBE. However, sera from animals exposed to serotypes of A.
      pleuropneumoniae other than serotype 5 presented a significantly lower mean OD (P
      < 0.05) when the LC-LPS was used. As a consequence, it was demonstrated that a
      high percentage of non-specific cross-reactions were eliminated, without losing
      specificity. The specificity and the sensitivity of the LC-LPS- and CBE-ELISA
      were evaluated using two different cut-off values (the OD plus two and three
      standard deviations) (SD) obtained from 593 sera from negative herds. The LC-LPS
      appeared a more suitable antigen than the CBE, since the sensitivity and the
      specificity (obtained with both thresholds) were statistically improved (P <
      0.01). A threshold of 0.244 (mean OD plus three SD) for the LC-LPS-ELISA seemed
      more suitable, since a sensitivity of 79% and a specificity of 97% was achieved.
      Nevertheless, it may be advisable to keep a buffer range (OD between 0.194 and
      0.243) and to consider sera presenting values within this range as suspicious. In
      the present study, the complement fixation test presented a high specificity
      (97%) and a very low sensitivity (47%). A herd with animals presenting ELISA
      positive and CFT negative results in serology, along with the absence of
      suggestive lesions should not be considered as a non-infected herd.

PMID- 8160348
TI  - Antigenic differences within Actinobacillus pleuropneumoniae serotype 1.
AB  - Two distinct antigenic subtypes of Actinobacillus pleuropneumoniae serotype 1
      were identified via coagglutination (Co-A) and designated as 1A and 1B. The
      reference strains, ATCC 27088 (1A) and ISU 158 (1B), were used to prepare
      hyperimmune rabbit sera for Co-A reagents. Of 75 serotype 1 field isolates tested
      by Co-A, 35 isolates typed as 1A, 12 as 1B and 28 as 1A/1B. Significant cross
      reactivity between the 2 subtypes was found in the Co-A and was eliminated in
      20/28 1A/1B strains by using Co-A reagents prepared with rabbit sera absorbed
      with the heterologous reference strain. However, twelve isolates (5 1A and 7
      1A/1B; 16%) showed no reaction with Co-A reagents prepared with absorbed sera.
      Immunoblots of outer membranes (OM) prepared from APP 1A or 1B reference strains
      and field isolates indicated that antigenic differences between subtypes 1A and
      1B were located within the high molecular weight (MW) region of the gels (40-100
      kDa). Hyperimmune rabbit sera against 1A or 1B and sera from pigs vaccinated with
      whole-cell, formalin inactivated 1A or 1B bacterins reacted with the high MW
      region only in strains of the homologous subtype. In contrast, 4 of 5 sera from
      1B infected pigs and 2 of 5 sera from 1A infected pigs reacted with all APP
      serotype 1 strains regardless of subtype. Apparently, infection exposed cross
      reactive antigenic determinants that were not exposed by immunization with killed
      bacteria preparations. SDS-PAGE gels with LPS purified from APP 1A, 1B, 9 and 11
      showed that 1A, 9 and 11 LPS O-antigens had an identical smooth ladder pattern,
      while 1B LPS was distinctly different. In immunoblots with OM or LPS and in dot
      immunobinding assays with LPS, rabbit antiserum against APP 1A reacted with 1A, 9
      and 11. In contrast, rabbit antiserum against APP 1B only reacted with APP 1B and
      weakly with APP 9 in the OM immunoblot and with LPS from APP 1B, 9 and 11 in the
      LPS immunoblot and dot-immunobinding assay. We conclude that 2 subtypes of APP
      serotype 1 can be distinguished based on their antigenic differences. These
      differences are located, at least in part, within the LPS O-antigens. LPS O
      antigens from APP 1B appear more antigenically similar to APP 9 LPS than to
      either APP 1A or APP 11 LPS. There may also be antigenic differences in the
      capsular polysaccharides of APP 1A and 1B strains.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8160349
TI  - Phenotypic characterization of Zimbabwean isolates of Pasteurella multocida.
AB  - The phenotypic characteristics of 60 Zimbabwean isolates of Pasteurella multocida
      sensu stricto, from disease syndromes in different host species were studied. A
      number of representative strains were also serotyped. Consistent results were
      obtained in the tests for; catalase, oxidase, urease, indole, acid in glucose,
      inositol, salicin and sucrose. There was no obvious relationship between
      serotype, host or disease and the pattern of utilization of certain substrates by
      an isolate. This has been discussed in the context of recent proposals to
      reclassify Pasteurella and P. multocida on genotypic and phenotypic studies. It
      is suggested that notwithstanding the relevance of genetic studies in
      circumscribing P. multocida, the phenotype and disease significance of the taxon
      should not be ignored. A case of bronchitis in a dog which was simultaneously
      colonized by three different strains of Pasteurella is described. Also
      septicaemic pasteurellosis in a Nile crocodile (Crocodylus niloticus) is reported
      and for the first time prevalence of various serotypes in pasteurellosis of
      animals in Zimbabwe.

PMID- 8160350
TI  - Evaluation of ELISA for detection of antibodies to CAEV in milk.
AB  - Milk was found to be a suitable alternative specimen for the serological
      diagnosis of caprine arthritis-encephalitis virus (CAEV) using the ELISA. The
      relative sensitivity and specificity of testing individual milk samples as
      compared to individual sera was 96.4 and 97.3% respectively. The overall
      agreement between the testing of milk and sera was 96.9% and the correlation
      coefficient between testing sera and milk, 0.94%. The testing of bulk milk could
      be used to predict approximately the prevalence of CAEV infection in a dairy goat
      flock. It was estimated that a prevalence of about 1.6% to 7.5% could be detected
      in the ELISA when bulk milk samples from two infected goat flocks were tested.
      Either chilled milk samples or milk samples treated with merthiolate were found
      to be suitable for testing.

PMID- 8160351
TI  - Immediate-early gene expression and gene mapping comparisons among isolates of
      bovine herpesvirus 1 and 5.
AB  - Bovine herpesviruses (BHV) are associated with a variety of clinical syndromes.
      Bovine herpesvirus 1 isolates were placed into three genome subtypes based on
      restriction endonuclease analyses, which were loosely associated by clinical
      manifestation as BHV1.1 (respiratory), BHV1.2 (genital), and BHV1.3
      (encephalitic). More recently the encephalitic isolate has been classified BHV5.
      A comparison of the cytopathic effect (CPE) in fetal bovine lung cell cultures in
      the presence of cycloheximide showed that BHV1.1 and 1.2 isolates produced
      elongated, spindle-shaped CPE, whereas BHV5 produced more syncytial-like CPE.
      Each BHV-1 subtype synthesized four immediate-early transcripts. The sizes in kb
      were: 1.6, 3.4, 5.8, 7.5 (BHV1.1); 1.8, 3.6, 5.8, 7.5 (BHV1.2); and 1.8, 3.6,
      5.8, 8.6 (BHV5). These transcripts were mapped to the inverted repeat region of
      each isolate by Southern blot hybridization using cDNA prepared from
      cycloheximide-treated BHV1-infected cellular polyA RNA. A possible unique
      immediate-early RNA may be produced by the BHV5 encephalitic isolate from an area
      of the internal repeat region unique to this isolate. Hybridization analysis
      using BHV1.1 cloned probes of the immediate-early protein gene, thymidine kinase
      gene, DNA binding/DNA polymerase gene, and glycoprotein III gene provided
      information for mapping of these genes to the BHV5 encephalitic isolate.

PMID- 8160352
TI  - Distribution of lymphocyte subpopulations in thymus, spleen, and peripheral blood
      of specific pathogen free pigs from 1 to 40 weeks of age.
AB  - Using flow-microfluorometry analysis and cluster determinant (CD) markers, we
      studied how lymphocyte subpopulations in lymphoid organs of specific-pathogen
      free pigs developed in pigs from birth to young adulthood. Cell suspensions of
      the thymus and spleen were prepared and peripheral blood cells were collected at
      1, 4, 10, and 40 weeks of age. Tissue sections of the thymus and spleen were
      stained with monoclonal antibodies directed against CD2 and immunoglobulin to
      localize the CD2-Ig- lymphocyte subpopulation. In the thymus, only limited
      changes were observed in the lymphocyte subpopulations with time. Most thymocytes
      expressed CD4 or CD8 or both. Most CD2-Ig- cells or, 'null cells', (5-13%) were
      observed in the medulla of the thymus and probably represented a recirculating
      cell type. In the spleen and blood the percentage of CD2+ and Ig+ cells increased
      significantly with time, the former increasing from about 30-60% owing to an
      increase of CD8+ cells. Therefore, the selective increase of the CD8+ population
      also caused the CD4/CD8 ratio to change. Although CD2+ cells in the spleen and
      blood are positive for CD4 or CD8, but not for both, quantities of CD4+ CD8+
      cells were also observed. Half of the lymphocytes in the spleen and blood were
      typed as null cells at 1 week of age and decreased in proportion to the increase
      of the CD8+ and Ig+ cells. Nevertheless, quantities of null cells were still
      present in the spleen blood at 40 weeks of age. Almost all these were located in
      the red pulp of the spleen. This study indicates an effect of age and housing
      conditions on the distribution of the lymphocyte subpopulations, and especially
      on the CD8+ subset. Quantities of CD4+CD8+ cells as well as CD4-CD8- were
      observed in blood, but also in spleen of pigs. The function of high numbers of
      null cells directly after birth are discussed.

PMID- 8160353
TI  - Heterogeneity of bovine IgG2. VI. Comparative specificity of monoclonal and
      polyclonal capture antibodies for IgG2a (A1) and IgG2a (A2).
AB  - The relative specificity of 26 randomly selected polyclonal and monoclonal anti
      bovine IgG2 reagents for the A1 and A2 allotypic variants of IgG2a was evaluated
      in a direct RIA using the reagents as solid-phase capture antibodies (CAbs). More
      than 70% of these reagents were significantly allotype-biased and > 80% of those
      were positively biased to IgG2a (A1). Compared as the ratio of the ng of IgG2a
      (A1) bound versus ng IgG2a (A2) bound per 50 ng added (Krel), bias for IgG2a (A1)
      of six of these reagents was greater than two-fold. Compared in terms of their
      solid-phase equilibrium constants (Keq), differences as great as two-logs among
      these reagents were observed. Steward-Petty plots suggested that differences in
      Krel of a select panel of reagents was usually due to differences in Keq, but for
      two reagents with large differences in Krel, the existence of one population of
      CAbs recognizing an allotope and another recognizing common IgG2a determinants,
      was indicated. Eight of ten guinea pigs immunized with IgG2a (A1) responded with
      highly significant specificity bias for A1 whereas only two of 11 rabbits and two
      of ten guinea pigs immunized with IgG2a (A2) responded weakly with preference for
      IgG2a (A2). These results concur with the concept of the immunodominant nature of
      the A1 allotope, but also suggest that immunization with IgG2a (A2) might be a
      practical means of avoiding allotype bias in IgG2a reagents. The data indicate
      that the majority of randomly selected anti-bovine IgG2 reagents are allotype
      biased to the extent that when used as serological reagents to measure total IgG2
      or bovine IgG2 antibody responses, the allotype of the animal tested rather than
      its total IgG2a concentration or IgG2 antibody titer, can determine the outcome
      of the serological test.

PMID- 8160354
TI  - Distribution of Ia antigen positive cells in chicken embryos infected with
      oncogenic Marek's disease virus (MDV) and MD vaccine viruses of serotypes 1, 2
      and 3.
AB  - Chick embryos infected at Day 13 of embryonic development (ED) with the oncogenic
      serotype 1 Marek's Disease Virus, isolate B (MDV-B) and three MDV vaccines
      (CVI988, SB1 and HVT, serotypes 1, 2 and 3, respectively) and uninfected chick
      embryos were studied for the distribution of Ia antigen positive dendritic cells
      (DC), B cells and MDV antigen positive (Ag+) cells in the lymphoid organs and
      chorioallantoic membrane (CAM). The immunofluorescence study was conducted on
      acetone-fixed organ touch impressions using monoclonal antibodies to Ia antigen,
      and MDV serotypes 1, 2 and 3 and polyclonal antibodies to bursal Ig-bearing (Ig+)
      B cells. DC were found mainly in the thymus and spleen and Ig+ cells in the
      bursa, thymus and spleen of normal embryos. All virus-infected embryos had MDV
      Ag+ cells in the spleen. MDV-B and SB1 infected embryos also had MDV Ag+ cells in
      the bursa, MDV-B Ag+ cells in the CAM and SB1-Ag+ cells in the thymus. Infection
      with MDV altered the distribution pattern of DC in a serotype-specific manner: to
      a lesser extent, infection with MDV-B and SB1 induced their appearance in the
      CAM, while HVT and CVI988 depleted the DC population from all organs except the
      bursa and the thymus, respectively. Infection with MDV-B depleted the Ig+ cells
      from all organs. These results suggest that virus-specific patterns of change in
      the distribution of DC and B cells occur in various tissues and organs of the
      chick embryo as a result of infection with oncogenic and apathogenic strains of
      MDV.

PMID- 8160355
TI  - In vitro effects of live and killed Brucella abortus on bovine cytokine and
      prostaglandin E2 production.
AB  - Live and gamma-irradiated-killed Brucella abortus strain 2308 increased
      interleukin 1 (IL-1), but not interleukin 2 (IL-2), interferon-gamma (IFN-gamma),
      or prostaglandin E2 (PGE2) production when incubated with normal bovine
      peripheral blood mononuclear cells (PBMC). Live B. abortus was more effective
      than killed B. abortus in stimulating IL-1 production by normal PBMC. Both live
      and killed B. abortus were equally effective in suppressing IL-2 and IFN-gamma
      production by Concanavalin A-stimulated PBMC. Incubation of PBMC with the cyclo
      oxygenase inhibitor, indomethacin, blocked PGE2 synthesis, but did not further
      enhance IL-1 production or prevent suppressed IL-2 and IFN-gamma production that
      was induced by live and killed B. abortus. These results suggest that B. abortus
      induced suppression of IL-2 and IFN-gamma production did not appear to be
      mediated by the suppressive prostaglandin, PGE2, or other cyclo-oxygenase
      metabolites.

PMID- 8160356
TI  - Monoclonal cytoplasmic immunoglobulin and pathomorphological reactions in lymph
      nodes in spontaneous bovine leukemia virus infection.
AB  - Prescapular lymph nodes from 109 cows seropositive to bovine leukemia virus (BLV)
      were examined for the presence of light chains of bovine immunoglobulin (Ig)
      kappa or lambda. A variety of reactions were present in prescapular lymph nodes,
      including B-zonal hyperplasia (23 cases, 21.1%), T-zonal hyperplasia (52 cases,
      47.7%), mixed hyperplasia (18 cases, 16.5%), pulp proliferation (six cases,
      5.5%), and atrophy (ten cases, 9.2%). In the case of pulp proliferation the
      immunohistological examination identified only Ig of a single light chain type
      lambda. The possible relationship of a monoclonal expression of Ig and
      development of tumorous proliferation is discussed in the study.

PMID- 8160357
TI  - Primary infection of dogs with Echinococcus granulosus: systemic and local
      (Peyer's patches) immune responses.
AB  - Local and systemic lymphocyte proliferation and antibody production were tested
      in five dogs 35 days after primary experimental infection with Echinococcus
      granulosus. A significant cell proliferation was demonstrated by [3H] thymidine
      incorporation in mesenteric, popliteal and/or Peyer's patches (PPs) cells in
      response to E. granulosus protoscolex or adult worm antigen in three of five
      infected dogs, but not in five control animals. In contrast, blood mononuclear
      cells responded very weakly in only two of the infected dogs to parasite
      antigens. Elevated levels (compared with preinfection status) of protoscolex- and
      adult worm antigen-specific serum IgG were detected (ELISA) in four of the five
      dogs 35 days after infection. Furthermore, slightly elevated levels of parasite
      specific IgE and IgA were observed in the sera of three and four in four infected
      dogs, respectively. Specific serum IgM was not significantly higher 35 days after
      infection than before infection. Local antibody production was studied in vitro
      using PPs, mesenteric and popliteal cells isolated from three infected and three
      uninfected dogs by ELISA using adult worm antigen. In two of three cultures of
      unstimulated PPs cells of infected dogs, parasite-specific IgG was detectable.
      Parasite-specific IgA and IgM were detected in one of the unstimulated PPs cell
      culture derived from an infected dog. Following in vitro stimulation with
      parasite antigen, PPs cells from two infected dogs showed increased parasite
      specific IgG and PPs cells of all three infected dogs produced parasite-specific
      IgA. PPs cells from uninfected dogs did not produce significant quantities of
      parasite-specific antibodies and cells from mesenteric and popliteal lymph nodes
      of infected or uninfected dogs neither produced antibodies whilst in in vitro
      cultures.

PMID- 8160358
TI  - Detection of bovine interleukin 1 alpha and interleukin 1 beta gene expression by
      reverse transcription-polymerase chain reaction.
AB  - Interleukin 1 (IL-1) is a cytokine that mediates a variety of immunoregulatory
      and inflammatory activities. Its role in proliferation of helper T cells is
      particularly important in the initiation of immune responses. Bovine interleukin
      1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta) mRNA expression was
      detected by reverse transcription-polymerase chain reaction (RT-PCR) technique in
      bovine peripheral blood mononuclear cells (PBMCs). Poly (A) + RNAs isolated from
      PBMCs by guanidium thiocyanate/oligo (dT)-cellulose chromatography extraction,
      were reverse-transcribed and the complementary DNAs amplified in a polymerase
      chain reaction primed with bovine IL-1 alpha and IL-1 beta sequence-specific
      primers. RT-PCR products were analyzed by agarose gel electrophoresis. As a
      result of the amplification of specific cDNAs by 35 cycles of PCR, the IL-1 alpha
      mRNA was detected from 0.01 ng of poly (A) + RNA, and IL-1 beta mRNA was detected
      from 0.1 pg of poly (A) + RNA isolated from PBMCs stimulated with
      lipopolysaccharide (LPS) for 4 h. Using 5 ng of poly (A) + RNA isolated from
      fresh bovine PBMCs unstimulated with any mitogen as template for RT-PCR, both IL
      1 alpha and IL-1 beta mRNAs were detected at a low level.

PMID- 8160359
TI  - Differential distribution of gamma delta T-cell receptor lymphocyte
      subpopulations in blood and spleen of young and adult cattle.
AB  - A panel of monoclonal antibodies to bovine leukocyte differentiation molecules
      was used to evaluate peripheral blood and splenic lymphocytes from cattle of
      various ages. The major population of peripheral blood lymphocytes from neonatal
      calves was gamma delta T-cell receptor (TCR1) positive, as determined by TCR1-N12
      expression. TCR1-N12+ lymphocytes were decreased in number in older calves, and
      were lowest in adult cattle. The major subpopulation of TCR1-N12+ cells from
      peripheral blood coexpressed WC1, but not BoCD2. A small subpopulation of
      peripheral blood TCR1-N12+ cells from cattle of all ages coexpressed BoCD2, but
      not WC1. The TCR1-N12+ BoCD2+ lymphocytes made up the largest TCR1-N12+
      lymphocyte subpopulation in spleens of both calves and adults. The TCR1-N12+WC1+
      splenic lymphocytes were present as a small population. The data indicate that
      two subpopulations of TCR1+ lymphocytes are present in cattle of all ages. These
      two subpopulations are differentially distributed between blood and spleen, with
      TCR1-N12+WC1+ lymphocytes predominating in blood, and TCR1-N12+BoCD2+ cells
      predominating in spleen.

PMID- 8160360
TI  - Porcine lymphocyte gamma interferon responses to mitogenic stimuli monitored by a
      direct immunoassay.
AB  - Gamma interferon produced by porcine lymphocytes (nPoIFN gamma) in response to
      stimulation with phorbol-myristate-acetate (PMA) and phytohemagglutinin (PHA) was
      monitored by a radioimmunoassay (RIA). The RIA was developed with antibodies
      raised in rabbits against recombinant porcine IFN gamma (rPoIFN gamma) and made
      monospecific on a rPoIFN gamma/Sepharose matrix. This anti-PoIFN gamma antibody
      was shown to bind and neutralize rPoIFN gamma specifically and to cross-react
      with bovine IFN gamma but not with murine IFN gamma or porcine IFN alpha. The
      nPoIFN gamma levels produced by lymphocytes in response to PMA and PHA were at
      least two-fold higher than control lymphocytes as measured by the RIA in culture
      fluids. These culture fluids were fractionated on Concanavalin A Sepharose (Con
      A/Seph) and anti-rPoIFN gamma/Seph in attempts to evaluate the induced nPoIFN
      gamma further. The separation was monitored by RIA and showed that nPoIFN gamma
      was retained on Con A/Seph suggesting the presence of sugar residues on the
      molecules. Pools of Con A/Seph fractions, positive in RIA, were separated further
      on the anti-rPoIFN gamma/Seph matrix where a total adsorption of nPoIFN gamma
      occurred. On a weight basis, the eluates from the anti-rPoIFN gamma/Seph had a
      reactivity in RIA at least four times higher than the fractions derived from Con
      A/Seph. This indicated that the nPoIFN gamma remained immunochemically reactive
      after being eluted from Con A/Seph and that the separation on anti-rPoIFN
      gamma/Seph chromatography was specific. Purified nPoIFN gamma exhibited a major
      band with the same migration characteristics of rPoIFN gamma in PAGE-SDS
      electrophoresis and several minor bands when reacted with 125I anti-rPoIFN gamma
      antibody in Western blots. A total loss of reactivity to antibody after
      radioiodination of nPoIFN gamma, however, prevented the confirmation of these
      results by immunoprecipitation. A direct, rapid and sensitive immunoassay for
      measurement of the relative levels of nPoIFN gamma present in biological fluids
      is presented and this method could be a useful complement to bioassays for IFN
      gamma.

PMID- 8160361
TI  - Evaluation of several adjuvants as alternatives to the use of Freund's adjuvant
      in rabbits.
AB  - In three experiments we evaluated several types of adjuvants as an alternative to
      Freund's adjuvant (FA). In the first experiment three adjuvant preparations (a
      water-in-oil emulsion (Specol), a combination preparation of monophosphoryl lipid
      A + trehalose dimycolate + cell wall skeleton and a non-ionic block polymer
      surfactant (TiterMax)) were evaluated. The adjuvants were combined with three
      different types of weak immunogenic antigens (synthetic peptide, glycolipid and
      particulate antigen) and administered following the intramuscular and
      subcutaneous route. The evaluation was based on clinical, pathological and
      immunological parameters. The animals did not appear to be severely or
      chronically impaired by the experiment. After injection of the RIBI adjuvant,
      side effects of the same severity as with FA were induced, while low antibody
      titers were produced. TiterMax caused few side effects, while antibody responses
      were very low. In comparing Specol and FA, Specol had far fewer adverse effects
      than FA. However, Specol had immunostimulating properties of the same level as
      FA. In the second experiment, the effect of injected volume of FA on side effects
      and antibody titer was studied. Immunization of rabbits with a total of 0.5 ml FA
      at different sites does not seem to increase the immune response when compared
      with the immune response seen after injection of 0.5 ml FA at one site. However
      side effects were seen in all the animals. In the third experiment, the side
      effects following intradermal (i.d.) injection of the adjuvants were studied.
      After i.d. injection of FA or RIBI, undesirable effects were found. No side
      effects occurred after i.d. injection of Specol or TiterMax. From the studies it
      is concluded that Specol is an alternative to FA for hyperactivation of the
      immune response in rabbits.

PMID- 8160362
TI  - Production and characterization of a monoclonal badger anti-immunoglobulin G and
      its use in defining the specificity of Mycobacterium bovis infection in badgers
      by western blot.
AB  - A mouse monoclonal anti-badger IgG antibody was produced to investigate the
      specificity of the antibody response of badgers infected with Mycobacterium
      bovis. The monoclonal antibody generated was directed against badger IgG heavy
      chain and appeared to be species restricted, reacting only with badger and dog
      IgGs but not cat, rabbit, mouse, guinea pig, bovine or ferret IgGs. This
      monoclonal antibody detection system functioned well in both ELISA and Western
      blot analyses and was successfully used to investigate the humoral response of
      the badger to M. bovis infection. Sera from infected badgers detected a 25 kDa
      antigen which was not detected by sera from M. bovis culture-negative animals.
      This antigen was conserved in all field strains of M. bovis tested and
      seroconversion to it was detected during experimental infection. The
      immunodominance of this antigen in the badger during infection with M. bovis
      suggests that this 25 kDa polypeptide is a suitable candidate on which to base an
      antibody detection test for M. bovis infection.

PMID- 8160363
TI  - A study of autoantibodies to phosphatidyl-serine in Babesia bovis and Babesia
      bigemina infections in cattle.
AB  - Sera from cattle infected with Babesia bovis were found to contain antibodies to
      phosphatidyl-serine (PS), a negatively charged phospholipid normally found on the
      internal membrane of erythrocytes. In contrast, no autoantibodies were detected
      following Babesia bigemina infection indicating that the autoimmunity is not
      genus specific. During infection with Babesia bovis, PS translocates to the
      external membrane and it is suggested that this may result in PS behaving as an
      autoantigen owing to a transitional change. These autoantibodies may also play
      some role in the pathology of infection, especially the disturbed coagulation
      system associated with acute Babesia bovis infection.

PMID- 8160365
TI  - Effects of optically induced blur on the refractive status of young monkeys.
AB  - In each of eight rhesus monkeys, one eye was defocused with a -9 D contact lens
      beginning before 1 month of age for periods of 2-3 months. At the end of the
      rearing period, interocular comparisons showed that one subject had developed a
      relative axial myopia (3.0 D), however, five monkeys had developed a relative
      axial hyperopia (2.0-3.5 D). After discontinuing the contact-lens rearing
      procedure, the induced refractive errors diminished over time in all subjects.
      These results indicate that the defocus threshold for form-deprivation myopia is
      relatively high and that substantial levels of optical defocus which do not
      exceed this threshold typically produce axial hyperopia. The recovery data
      suggests that monkeys have an emmetropization mechanism which is sensitive to
      optical defocus, but the failure of this mechanism to compensate for the
      refractive errors simulated during the lens-rearing procedures suggests that this
      mechanism has a limited operating range.

PMID- 8160364
TI  - The intrarhabdomal filters in the retinas of mantis shrimps.
AB  - The intrarhabdomal filters in the photoreceptors of compounds eyes of 32 species
      of mantis shrimps (Crustacea: Stomatopoda), representing seven families within
      the superfamilies Lysiosquilloidea and Gonodactyloidea, were surveyed by
      microspectrophotometry of filters in fresh cryosections of the retina. A total of
      up to four classes of filters exist in stomatopods: two each in Rows 2 and 3 of
      the midband. All lysiosquilloid species lacked the proximal filter in Row 3; a
      few also lacked the proximal Row 2 class. While most gonodactyloid species had
      all four possible classes, in some species the proximal filters of Row 3 and (in
      one case) Row 2 were missing. In all, at least 11 distinct spectral classes of
      pigments were found. Absorption spectra suggested that the filter pigments were
      probably carotenoids or carotenoproteins, although the distal filter of Row 3 was
      often exceptional, appearing to contain a mixture of pigments. While the types of
      pigments found in the filters of the various species generally followed taxonomic
      lines, numerous exceptions were found that were apparently related to the
      ecological requirements of the various species.

PMID- 8160366
TI  - Spatial integration in human vision with bichromatically-mixed adaptation field.
AB  - The present study showed that the spatial integration area was expanded even if
      the background energy was increased, provided that the background consisted of
      the two colors which were opponent to each other (red/green). This expansion was
      not found for the subjects with dichromatic color vision even though the same
      condition was utilized. It was suggested that polarization and its release (the
      change of adaptation level) of the chromatically-opponent red/green system were
      involved in control of spatial integration area.

PMID- 8160367
TI  - The influence of a stationary single line in darkness on the visual perception of
      eye level.
AB  - The angle of pitch of a visual field consisting of only a single vertical, 64
      degrees-long, eccentrically-located line in otherwise total darkness influences
      the elevation of a target set to appear at eye level (VPEL). The influence
      changes linearly with the magnitude of pitch over the range from -30 degrees to
      +20 degrees. The average slope of the VPEL-vs-pitch function is +0.53. The
      influence on VPEL of a pitched visual field consisting of two parallel vertical
      lines is slightly greater (slope = +0.56), and the influence of the pitch of a
      complexly-structured well-illuminated pitched room is slightly greater yet (slope
      = +0.63). The pitch of a frontoparallel plane containing one horizontal line has
      a small influence on VPEL (slope = +0.08); the influence with two horizontal
      lines is slightly greater (slope = +0.18). The slope of the VPEL-vs-pitch
      function differs among individual subjects but is linear for each of the eight
      subjects. A great deal of consistency is manifested by individual subjects across
      all of the visual fields: an individual with a steep slope with one visual field
      tends to have a steep slope with all visual fields. The individual's
      characteristic response in total darkness is strongly correlated with the
      response to an erect well-illuminated visual field. The significant aspect of the
      pitched-from-vertical line stimulus is the change in orientation of its retinal
      image. An additional experiment with a small pupil (pilocarpine) indicates that
      cues related to other retinal gradients or to accommodation play no role in the
      influence of the visual field on VPEL. The experiments provide support for
      treating the visual influence on VPEL by means of the Great Circle Model.

PMID- 8160368
TI  - The spatial tuning of chromatic mechanisms identified by simultaneous masking.
AB  - We have investigated the spatial transfer characteristics of the mechanisms
      sensitive to color in the human visual system using a method of simultaneous
      spatial masking with isoluminant chromatic stimuli. The test stimuli were
      Gaussian enveloped red-green gratings of three spatial frequencies in the lowpass
      region of the color domain (0.25, 0.5 and 1 c/deg). The masking stimuli were red
      green gratings at the orientation and phase of the test, presented at the same
      spatial frequency, and at +/- 1, and +/- 2 octaves from its spatial frequency. We
      obtained test contrast threshold as a function of mask contrast for a wide range
      of mask contrasts (TvC functions). Tuning functions were derived from linear fits
      of the masking data, by taking the mask contrast that doubled the minimum test
      threshold at each spatial frequency. Chromatic tuning functions show bandpass
      characteristics for all test spatial frequencies examined with an average full
      bandwidth at half-height of 2.6 octaves, which is similar to the luminance
      bandwidths obtained under comparable conditions. Thus, our results suggest that
      the color contrast sensitivity function is the upper envelope of a range of
      bandpass mechanisms whose peaks extend to very low spatial frequencies.

PMID- 8160369
TI  - Spatio-temporal interpolation in depth.
AB  - Spatio-temporal interpolation creates the impression of motion from a rapid
      sequence of stationary images by reconstructing the motion path in between the
      stations actually presented. Thresholds below the diameter of foveal
      photoreceptors have been obtained with two-dimensional spatio-temporal
      interpolation. We found that also three-dimensional interpolation, i.e.
      interpolation in depth, where information from motion detectors tuned to opposite
      directions in both eyes has to be combined, yields thresholds in the hyperacuity
      range. The results of parametric experiments favour the interpretation that
      interpolation occurs at a monocular stage of visual processing, rather than on a
      stereoscopic stage.

PMID- 8160370
TI  - Movement aftereffect of bi-vectorial transparent motion.
AB  - Two moving random-pixel arrays (RPAs) were presented simultaneously in the same
      target field. These RPAs are perceived as two superimposed transparent moving
      sheets. Although two directions are perceived simultaneously during stimulus
      presentation, the movement aftereffect (MAE) is unidirectional. The visual system
      averages both motion signals in the MAE. For motion vectors of equal magnitude
      and perpendicular direction the MAE direction is the inverse of the sum of both
      vectors. In the first experiment we measured perceived direction of the MAE of
      transparent motion for a range of speed combinations. Results indicate that
      vector summation only predicts the correct MAE direction for combinations of
      equal speeds. It is suggested that the direction of the MAE of transparent motion
      is a resultant of the weighted summation of the component inducing vectors. The
      question then arises what determines the weighting factors. Directional
      sensitivity and MAE duration of the individual vectors under transparent
      conditions were measured and used to weigh the vectors and predict the MAE
      direction of transparent motion. Statistical analyses showed that MAE duration is
      a better basis to determine the weighting factors predicting the direction of the
      MAE of transparent motion than component sensitivity. The direction of the MAE of
      transparent motion thus seems to be determined by the amount of adaptation to the
      component vectors as reflected by MAE duration. The results suggest that this
      gain control cannot be located in the individual motion detectors and must be
      situated at or after some subsequent cooperation stage of the human motion
      analysis system.

PMID- 8160371
TI  - Color perception within a chromatic context: the effect of short-wavelength light
      on color appearance.
AB  - Light at the boundary of a uniform test field (contrast) has a qualitatively
      different effect on color perception than light in more remote noncontiguous
      regions (context). Basic properties of color perception with contextual short
      wavelength light are assessed here with a 1 degree test field surrounded by
      either contiguous or noncontiguous 440 or 491 nm light (32 td). Contrasting
      stimuli are 3 or 5 degrees adapting fields, a thin 1 degree i.d.-2 degrees o.d.
      (0.5 degree wide) contiguous band, or a large 1 degree i.d.-5 degrees o.d.
      contiguous surround. Contextual stimuli are a remote 3 degrees i.d.-5 degrees
      o.d. ring or 0.5 degree wide noncontiguous bands at various distances from the
      edge of the 1 degree test field (2 degrees i.d.-3 degrees o.d., 3 degrees i.d.-4
      degrees o.d., or 4 degrees i.d.-5 degrees o.d. bands). Contiguous surrounds have
      little influence on color appearance, but remote noncontiguous short-wavelength
      light strong affects the color of the test field, shifting it toward redness. The
      shift toward redness increases as a thin 440 nm band is moved farther from the
      test field (up to 5 degrees), unlike the effect of distance on remote middle- and
      long-wavelength bands. Measurements comparing the effects of 440 nm and luminance
      equated 491 nm light indicate a contribution from S cones.

PMID- 8160372
TI  - Individual differences in cone photopigments of normal trichromats measured by
      dual Rayleigh-type color matches.
AB  - Individual differences in color matches of normal trichromats are well
      documented. Recently, variants of the classical Rayleigh match have been measured
      to explore the cause(s) of these individual differences. Interobserver
      differences in the wavelength of peak sensitivity of photopigment (lambda max)
      are of primary interest because they are attributed to an X-chromosome-linked
      polymorphism. Color-matching equations, however, show the Rayleigh match cannot
      distinguish between interobserver differences in lambda max and interobserver
      differences in the optical density of photopigment. Further analysis of color
      matching equations reveals that the ratio of two particular Rayleigh-type matches
      amplifies the effect of individual differences in the lambda max of L cones
      relative to the effects of optical density and pre-receptoral spectrally
      selective filtering. The ratio of these two color matches was measured for 17
      color-normal males. The range of the results for the 17 observers is too large to
      be explained by only individual differences in photopigment optical density and
      pre-receptoral filtering. This implies there are interobserver differences in
      lambda max. The results are accounted for quantitatively by a small difference (3
      5 nm) in the lambda max of the L-cone photopigment. The ratio of two Rayleigh
      type matches is a rapid and convenient measurement for assessing the L-cone
      lambda max in the eye of an individual observer and therefore may be useful for
      classifying normal trichomats into phenotypic sub-types.

PMID- 8160373
TI  - Serine/alanine amino acid polymorphism of the L-cone photopigment assessed by
      dual Rayleigh-type color matches.
AB  - The dual Rayleigh-type color match is the ratio of 621 nm light to 550 nm light
      that in admixture matches 586 nm light, divided by the ratio of 667 nm light to
      550 nm light that in admixture matches 586 nm light. Compared to the classical
      Rayleigh match, the dual-match procedure minimizes variation in color matching
      arising from differences in lens pigmentation and photopigment optical density,
      and thus amplifies individual differences due to shifts in L pigment lambda max.
      We hypothesized that the dual matches would provide a clearer distinction between
      subjects with serine and subjects with alanine than would the classical Rayleigh
      match because individuals with serine express L pigments with a lambda max
      shifted toward longer wavelengths than do those with alanine. Classical Rayleigh
      color matches were compared with dual Rayleigh-type color matches in 14 color
      normal observers whose DNA had been analyzed previously for the presence of the
      amino acid serine or alanine at position 180 in the L opsin. The resulting
      distribution of dual-match measurements for the seven subjects with serine does
      not overlap the distribution of measurements for the seven subjects with alanine.
      The classical Rayleigh-match measurements for these two groups of subjects, on
      the other hand, overlap substantially. More than half of the subjects' classical
      Rayleigh matches are within the overlapping range. The dual Rayleigh-type
      matches, therefore, provide an improved psychophysical technique for assessing
      whether an individual observer has serine or alanine at position 180.

PMID- 8160374
TI  - The effect of stimulus contrast and interocular correlation on disparity
      vergence.
AB  - In previous reports, we developed a metric for describing the signal strength of
      a dynamic random-dot stereogram (DRDS) stimulus at binocular (cyclopean) levels
      of the human visual system, which takes both contrast and interocular correlation
      into account. In this study we tested the generality of that metric in relation
      to the control of horizontal vergence eye movements. Signal strength was assessed
      by measuring the extent to which a DRDS stimulus could elicit involuntary
      vergence responses from a subject who was attempting to fixate steadily. Results
      for both step and sinusoidal disparity modulation paradigms showed that vergence
      velocity increased when either interocular correlation (IOC) or contrast was
      increased. Furthermore, IOC and contrast were found to contribute to signal
      strength for vergence in the same proportion as was found psychophysically. In
      general, the results indicate that the signals that drive this passive form of
      vergence are derived according to the same binocular combination rules as the
      signals that give rise to the perception of surfaces in DRDS stimuli.

PMID- 8160375
TI  - Simultaneity in the Ternus configuration: psychophysical data and a computer
      model.
AB  - The Ternus configuration is an apparent motion display which is typically
      described as being bistable; subjects usually describe seeing either element
      motion or group motion, depending upon temporal properties of the display. The
      results of an experiment are reported in which subjects are also permitted to
      report seeing four stationary display elements (simultaneity). It was found that
      simultaneity was produced when both frame durations and interstimulus intervals
      (ISIs) were brief. A weaker than expected effect of stimulus onset asynchrony
      (SOA) was revealed because this third type of judgment was obtained. Furthermore,
      statistical analyses indicated that SOA was not by itself the best predictor of
      judgment type. The interaction between duration and ISI was also an important
      predictor. This suggested that a complete account of the Ternus configuration
      requires two mechanisms: a visible persistence mechanism, governed by an SOA law,
      and a motion correspondence mechanism, governed by an ISI law. These two
      mechanisms were added to Dawson's (1991) [Psychological Review, 98, 569-603]
      autoassociative network for motion correspondence processing. The resulting model
      could generate each of the three interpretations of the Ternus configuration at
      appropriate combinations of frame duration and ISI.

PMID- 8160376
TI  - Visual field deficits in early age-related macular degeneration.
AB  - Patients with early age-related macular degeneration (AMD) may retain good visual
      acuity but experience distortion and other qualitative visual changes. The
      purpose of the present study was to determine whether deficits of form
      recognition, as well as of light sensitivity, were related to retinal pigment
      epithelial (RPE) atrophy and/or drusen. We assessed form recognition deficits by
      the Amsler grid and by a perimetric test of letter recognition and sensitivity
      deficits by the macular threshold test of the Humphrey Field Analyzer in 59
      patients with AMD and visual acuities of 20/40 or better. The number of defects
      on each test was compared with the area of RPE atrophy and with the area of
      drusen determined from fundus photographs. Multiple regression analyses based on
      ordinal data revealed that the number of visual field defects by each test was
      significantly correlated with the area of atrophy, but not with the area of
      drusen. There was also no significant tendency for a patient with a regional
      preponderance of drusen to have more impairment in the corresponding visual
      field. These results suggest that deficits of form recognition, as well as of
      sensitivity, in patients with early stages of AMD can be attributed to alteration
      of photoreceptor function associated with RPE atrophy, but not with drusen.

PMID- 8160377
TI  - Immunocytochemical characterization and spatial distribution of midget bipolar
      cells in the macaque monkey retina.
AB  - Midget bipolar cells form the first distinct step in the parvocellular (P-)
      pathway of the primate visual system, and are the major determinant of the
      receptive field properties of colour selective midget ganglion cells. This paper
      describes the sampling properties of the midget bipolar cell population and
      relates this to the processing of chromatic information in the P-pathway.
      Immunocytochemical markers were used to label midget bipolar cells so that their
      spatial density could be compared with that of cones and ganglion cells. Sections
      through macaque monkey retinae were immunostained with antibodies against
      cholecystokinin (CCK), and recoverin. In CCK-labelled sections, in addition to
      blue cone bipolar cells, numerous thin bipolar cell dendrites, which could be
      associated with individual cone pedicles are stained. CCK-immunoreactive midget
      bipolar cells are found throughout the retina. A different population of midget
      bipolar cells is revealed in recoverin-labelled sections. Based on a comparison
      with midget bipolar cells in Golgi-stained retinae we propose that ON-midget
      (invaginating) bipolars are immunoreactive for CCK and confirm that OFF-midget
      (flat) bipolar cells are immunoreactive for recoverin [Milam, Dacey and Dizhoor
      (1993) Visual Neuroscience, 10, 1-12]. The density of recoverin labelled midget
      bipolars matches the cone density to an eccentricity of about 10 mm; from there
      outwards it drops to 60% of the cone density. This suggests convergence of
      several cones to individual midget bipolar cells in peripheral retina. We
      conclude that midget bipolar cells are present throughout the entire primate
      retina, and could, in peripheral as well as in central retina, provide
      chromatically specific input to the P-pathway.

PMID- 8160378
TI  - Hemispheric asymmetry in the maturation of the extrastriate checkerboard onset
      evoked potential.
AB  - Recently we have shown that the single positive deflection in the checkerboard
      onset evoked potential (EP) of young children of striate origin develops into a
      negative-positive complex. However, also an early positive peak becomes apparent
      in the checkerboard onset EP. To determine the origin and development of the
      activity underlying this early positive deflection we studied the checkerboard
      onset EPs in children of 9-16 years of age. It was found that for the children in
      this age group two different dipole sources are responsible for the activity
      underlying the pattern onset EP. One of the dipoles corresponds to the activity
      generated in the striate cortex, whereas a second dipole of extrastriate origin
      is responsible for the appearance of the early positive deflection. This
      extrastriate activity shows hemispheric asymmetry, i.e. the strength of the right
      hemispheric extrastriate source exceeds the strength of the left hemispheric
      source. These results are in accordance with histological studies of Conel (1939
      1963) [The postnatal development of the human cerebral cortex (Vols 1-8).
      Cambridge, Mass.: Harvard Univ. Press] which show that the maturation of the
      extrastriate areas of the left hemisphere is delayed with respect to the right
      hemisphere.

PMID- 8160379
TI  - Visual pigments and the photic environment: the cottoid fish of Lake Baikal.
AB  - The endemic cottoid fish of Lake Baikal in Eastern Siberia offer a singular
      opportunity for examining within a number of closely related species, the
      relationships of visual pigments, photoreceptor complements and depth within a
      deep freshwater environment. The lake, the deepest (1600 m) and one of the
      largest and most ancient in the world, is unique in that the oxygen levels at the
      bottom are only reduced to about 80% of the surface levels. We have studied, by
      light microscopy, microspectrophotometry and visual pigment extraction, the
      retinas from 17 species of Baikal cottoids that live at different depths within
      the lake. Generally the retinas contain, in addition to rods, large green
      sensitive double cones and small blue-sensitive single cones: surprisingly for
      freshwater fish, the visual pigments are based on Vitamin A1. The lambda max of
      both rods and cones are displaced to shorter wavelengths with increasing depth.
      Surface species have cones with lambda max at about 546, 525 and 450 nm and rods
      at 523 nm, deeper living species retain cones, but with lambda max shifting
      towards 500 and 425 nm and with rods at 480 nm, whereas the deepest living fish
      possess only rods (lambda max 480-500 nm). These data clearly show a correlation
      between photoreceptor complement, visual pigment lambda max and depth, but
      question the hypothesis that there is a correlation of pigment lambda max with
      water colour since, in contrast to oceanic waters, the maximum transmission of
      Baikal water is between 550 and 600 nm.

PMID- 8160380
TI  - Selectivity of cyclopean masking for the spatial frequency of binocular disparity
      modulation.
AB  - Previous studies have presented evidence for the existence of channels tuned to
      the spatial frequency (SF) of binocular disparity modulation. Bandwidths reported
      for masking curves were extremely narrow, possibly because of off-frequency
      viewing, whereby observers can best detect a signal with a channel tuned to an SF
      on the opposite side of the signal from the masker's SF, rather than with a
      channel tuned directly to the signal's SF. Herein are reported the results of
      four detection experiments. Experiment 1 measures unmasked threshold for
      detection of a cyclopean grating. Experiments 2-4 are masking experiments.
      Experiment 2 demonstrates that threshold for detection of a cyclopean grating is
      proportional to the intensity of masking noise, which is consistent with the
      operation of linear channels. Experiments 3 and 4 demonstrate that masking curves
      are narrower when obtained with narrowband-noise maskers than when obtained with
      notched-noise maskers, which render the off-frequency viewing ineffective.
      Implications for understanding the processing of cyclopean images are discussed.

PMID- 8160381
TI  - Scotopic center surround organization in 10-week-old infants.
AB  - The large critical areas for complete spatial summation in infants may be due to
      immaturities of receptive field organization in both dark and light adapted
      scotopic conditions. Scotopic lateral excitatory/inhibitory interactions have
      been previously studied in adults using Westheimer's [(1965) Journal of
      Physiology, London, 181, 881-894] paradigm. We modified this paradigm to
      investigate scotopic receptive field organization in infants. Detection
      thresholds for probe flashes of constant diameter and duration presented on
      steady backgrounds of various diameters were determined for 10-week-old infants
      and adults. Infants' thresholds increased up to background diameters of 3 degrees
      to 3.5 degrees and then decreased at greater background diameters. Adults'
      thresholds increased for backgrounds up to about 0.75 degrees diameter and then
      decreased at greater background diameters. These results suggest that the
      excitatory, central receptive field size is larger in infants than adults, and
      that a balanced center-surround mechanism is operative.

PMID- 8160382
TI  - The coding of spatial position by the human visual system: effects of spatial
      scale and retinal eccentricity.
AB  - In this study we investigate the nature of the computations that underlie the
      encoding of spatial position by the human visual system. Specifically, we explore
      the relationship between alignment accuracy and retinal eccentricity for stimuli
      where local luminance, local contrast, and orientation cues do not underlie
      performance. Spatial scale is especially important for such a comparison because
      of the well documented spatial inhomogeneity of the human visual field. The
      results suggest that the relationship between spatial localization and
      eccentricity is invariant with spatial scale if accuracy and eccentricity are
      expressed in terms of the stimulus envelope size. We show that the photoreceptor
      disarray does not determine the limit to performance for this task, the limit is
      post-receptoral and can be modelled in terms of a positional uncertainty within
      the early filters located before the response envelope has been extracted. This
      uncertainty varies with eccentricity in a similar way within each spatial array.

PMID- 8160383
TI  - A two-process analysis of pattern masking.
AB  - By comparing the masking effects of cosine gratings and uniform fields on
      spatially narrow-band test patterns, we obtain evidence that pattern masking is
      mediated by two stages of visual processing: an early process of point-wise
      luminance adaptation and a late process of spatial-frequency and orientation
      selective filtering. The early (presumably receptoral) component of masking is
      not affected by the polarity (incremental or decremental) or spatial frequency of
      test patterns, and may either increase or decrease pattern sensitivity based on
      local light level. The late masking process is orientation and spatial-frequency
      dependent, implying a cortical origin. For this cortical process, we find
      competitive interaction between parallel ON and OFF visual mechanisms: on a
      bright bar of a mask, threshold shift is greater for decremental than incremental
      tests, and the opposite is true on a dark bar of the mask. We suggest that ON-OFF
      interactions in pattern masking serve to normalize the gain of ON and OFF
      mechanisms simultaneously in order to preserve the relative contrast in the
      image.

PMID- 8160384
TI  - On the role of X and simple cells in human contrast processing.
AB  - We investigated the potential role of retinal X and cortical simple cells in
      determining human psychophysical detection performance under contrast masking
      conditions. Since both X and simple cells exhibit a null phase, the phase of a
      background mask should affect the visibility of a test grating processed by such
      cells. Sinusoidal test gratings of either 1 or 7 c/deg were presented as a
      sustained or transient increment against a background mask of the same size and
      spatial frequency at either 0 or 90 deg phase. For background contrasts from 0.5%
      up to 40%, psychophysical contrast sensitivity was phase-independent for all
      conditions. Therefore, either (1) contrast threshold is mediated by cells with
      non-linear spatial summation properties, such as Y or complex cells, or (2) the
      masking effect of the background occurs after a phase-insensitive combination or
      pooling of simple cell responses in the cortex.

PMID- 8160385
TI  - Probabilistic analysis of human supervised learning and classification.
AB  - Probabilistic classification techniques based on Bayesian decision theory are
      used to analyze human supervised learning and classification. The procedure rests
      on the assumption that human classification behaviour is based on internal
      feature states which can be linked to physical feature vectors (corresponding to
      the system input). In the present approach, this relationship is modeled in terms
      of additive stochastic error signals. The corresponding random variables describe
      the additional degrees of bias and variance introduced by the (perceptual)
      process of internal feature measurement. Estimates of internal feature states are
      obtained by least-squares minimization. Structure and dimensionality of the
      resulting internal representation are displayed by plotting the configuration of
      internal class means, or virtual prototypes. Their temporal evolution reflects
      the dynamic properties of the learning process. The use of the procedure is
      demonstrated by analyzing the results of two experiments. First, it is shown that
      Minimum Distance Classifiers, such as used by Caelli, Rentschler and Scheidler
      [(1987) Biological Cybernetics, 57, 233-240], are suboptimal in predicting human
      performance. Second, it is found that extrafoveal learning is much slower than
      foveal learning and that extrafoveal pattern representations are severely
      distorted. The latter distortions reveal the existence of limitations for the
      generalization of supervised learning over space.

PMID- 8160386
TI  - Pointing errors in strabismics: complex patterns of distorted visuomotor
      coordination.
AB  - Monocular eye-hand coordination was tested in a pointing experiment in the
      central and peripheral visual field of each eye of strabismic and anisometropic
      amblyopes, strabismic alternators and normal controls. In the normal controls,
      pointing was accurate in the central visual field. Towards the periphery, normal
      observers showed a varying amount of undershoot as well as increasing
      uncertainty. The pointing pattern was similar in the two eyes of these subjects.
      Increased uncertainty of pointing responses was found in most amblyopic eyes as
      compared to the dominant eyes. Three strabismic amblyopes and one strabismic
      alternator also had systematic pointing errors (i.e. systematic differences
      between pointing under the control of the dominant as compared to the nondominant
      eye). The pointing pattern was not uniform across the visual field in some of the
      strabismics, but was composed of areas of larger and smaller pointing errors.
      Larger pointing errors (i.e. larger differences between the dominant and
      nondominant eyes) were usually found in the central visual field. These errors
      were not closely related to the angle of squint. The clinical history of the
      strabismics seems to be an important factor for the occurrence of pointing
      errors.

PMID- 8160387
TI  - Functional postnatal development of the rat primary visual cortex and the role of
      visual experience: dark rearing and monocular deprivation.
AB  - Postnatal development of rat visual cortical functions was studied by recording
      extracellularly from the primary visual cortex of 22 animals ranging in age from
      postnatal day 17 (P17) to P45. We found that in the youngest animals (P17-P19)
      all visual cortical functions tested were immature. Selectivity for orientation
      and movement direction of visual stimuli was almost absent, most cells received
      binocular input and their mean receptive field size was 5-6 times the adult size.
      Visual acuity was half its adult value. These functional properties developed
      gradually during the following weeks and by P45 they were all adult-like. This
      functional development is affected by manipulations of the visual input such as
      dark rearing (DR) and monocular deprivation (MD). DR prevented the normal
      postnatal maturation of visual cortical functions: in P60 rats, dark reared from
      birth, their visual cortical functions resembled those of P19-P21 rats. MD from
      P15 to P45 resulted in a dramatic shift of the ocular dominance distribution
      (ODD) in favour of the open eye and in a loss of visual acuity for the deprived
      eye. To determine the sensitive period of rat visual cortex to MD (critical
      period) we evaluated the shift in ODD of visual cortical neurones in rats that
      were subjected to the progressive delay of the onset of fixed MD period (10
      days). Our results show that the critical period begins around the end of the
      third postnatal week, peaks between the fourth and fifth week and starts to
      decline from the end of the fifth week.

PMID- 8160388
TI  - Organization of contour from motion processing in primate visual cortex.
AB  - A major objective of visual processing is the segmentation of the scene into
      separate objects. Relative motion is one of the most salient segmentation cues.
      In man and monkey, we recorded visually evoked potentials to a stimulus, designed
      to signal the presence of relative motion processing. Relative motion specific
      response components were only elicited when human observers perceive contours
      from relative motion. Equivalent dipole source localization of the responses
      indicated the involvement of primary visual cortex in man. This was corroborated
      by intracortical recordings in awake monkey, where sources of the specific
      components are located within the supra- and infragranular layers of primary
      visual cortex. It is concluded that V1 does not merely provide an input stage to
      contour from motion processing, but that segmentation information, based on
      relative motion, is present at this early cortical level.

PMID- 8160389
TI  - Spatial-frequency-tuned channels in early infancy: VEP evidence.
AB  - Spatial frequency (SF) adaptation of 3-, 6-, and 12-week-old infants produced
      changes in steady-state VEP amplitude to SF sweeps that closely resemble post
      adaptation changes reported previously in adults. Following SF adaptation, VEP
      amplitude was attenuated to SFs near the adapting SF, and enhanced at SFs removed
      from the adapting SF in all age groups. This is interpreted as evidence for
      bandpass SF-tuned channels with coinhibitory interactions. The data presented
      here, in combination with VEP estimates of infant acuity, imply the existence of
      multiple bandpass SF-tuned channels with inhibitory relationships by 3 weeks of
      age. We hypothesize that neonatal spatial frequency filters are qualitatively
      adultlike.

PMID- 8160390
TI  - Motion displacement thresholds for compound stimuli predicted by the displacement
      of centroids.
AB  - Minimum displacement thresholds were measured using a compound motion stimulus,
      in which a single bar split into oppositely moving components, having different
      luminances and absolute displacements. The results fit a simple model in which
      observers detect the movement of the centroid of the combined luminance pattern
      of the two components. This was so even when the two components were separated by
      more than the static spatial resolution limit of 30 sec arc.

PMID- 8160391
TI  - Separable red-green and luminance detectors for small flashes.
AB  - Detection contours were measured in L and M cone contrast coordinates for foveal
      flashes of 200 msec duration and 2.3, 5, 10 and 15 min arc diameter on a bright
      yellow field. The test flash consisted of simultaneous incremental and
      decremental red and green lights in various amplitude ratios. At all sizes, the
      most sensitive detection mechanism was not a luminance mechanism, but rather a
      red-green mechanism that responds to the linear difference of equally weighted L
      and M cone contrasts, and signals red or green sensations at the detection
      threshold. Both temporal and spatial integration were greater for red-green
      detection than luminance detection. A coincident, subthreshold, yellow flash (a
      luminance pedestal) did not affect the threshold of the red-green mechanism. Such
      a pedestal is a sum of equal L and M cone contrast--it represents a vector
      parallel to the red-green detection contour and thus is expected not to stimulate
      directly the red-green mechanism. When suprathreshold, the coincident pedestal
      facilitated chromatic detection by approximately 2x at all tested sizes; intense
      pedestals did not mask chromatic detection. This insensitivity to intense
      luminance pedestals further indicates that the red-green mechanism has fixed
      spectral tuning with balanced opponent L and M contrast inputs. This view of
      fixed spectral weights contrasts with the "variable tuning hypothesis", which
      postulates that the weights change with spatial-temporal variations in the test
      stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8160392
TI  - Detection and direction discrimination performance with flicker gratings in
      peripheral vision.
AB  - Detection and direction discrimination experiments were conducted with luminance
      and flicker gratings. The flicker gratings had bars made up of static random
      pixels interspersed between other bars with flickering random pixels. All
      experiments were carried out in peripheral vision with grating images centered at
      8 deg eccentricity in the superior retina. Detection of flicker gratings (i) was
      independent of pixel size, (ii) declined with spatial frequency in the range 1-4
      c/deg, and (iii) improved with stimulus area (number of grating cycles).
      Detection performance with a flicker grating was comparable to that obtained with
      a low-contrast (0.01) luminance grating, and the results suggest that the spatial
      structure of a flicker-domain stimulus is based upon signals which are weak
      compared to the maximum signals attainable with a luminance-domain stimulus. With
      the detectability of flicker and luminance gratings equated, d' for
      discriminating the direction of motion of a luminance grating increased with step
      size (1/12 to 1/4 cycle) whereas direction discrimination performance with a
      flicker grating remained unchanged and at chance levels. Under the conditions
      tested, there was no evidence that the motion of a flicker-domain stimulus could
      be processed peripherally. Constraints on alternative models of motion processing
      are discussed.

PMID- 8160393
TI  - Changes in the perceived direction of drifting plaids, induced by asymmetrical
      changes in the spatio-temporal structure of the underlying components.
AB  - When a plaid pattern with symmetrical velocity components (Type I) is changed to
      a plaid pattern with asymmetrical velocity components (Type IA), the overall
      direction of drift appears to undergo a rotation without any other change to the
      spatial parameters of the components. This change in the perceived drift
      direction can be induced by altering either the temporal frequency of the
      components or by altering their spatial frequency. In separate experiments, we
      have estimated the magnitude of the temporal and spatial frequency thresholds
      that are necessary to create a liminal change in direction of this type. The
      results from both temporal and spatial frequency experiments are closely similar.
      We find that liminal rotations can be induced by changes in the spatio-temporal
      structure of the sine-wave grating components that are undetectable when these
      components are presented in isolation. Further, we find that the "velocity
      threshold for direction" is not a constant factor, but critically depends on the
      relative orientation of the two elements that form the plaid. Forced-choice
      experiments were also conducted to estimate the extent of the apparent rotation
      of the plaid pattern for differing levels of asymmetry in the spatial frequency
      and temporal frequency of the components. The magnitude of the pattern rotation
      is predicted by a model of motion direction that encodes the successive
      displacements of the intersections of the gratings. Finally, we demonstrate that
      the velocity thresholds for perceived rotation exhibit a meridional anisotropy
      that depends on the direction of drift of the overall pattern and not on the
      orientation of the components.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8160394
TI  - Stereopsis and positional acuity under dark adaptation.
AB  - Though experience tells us we can perceive depth in dim light, it is not so
      obvious that one of the chief mechanisms for depth perception, stereopsis, is
      possible under scotopic conditions. The only studies on human stereopsis in the
      dark adapted state seem to be those of Nagel [(1902) Zeitschrift fur Psychologie,
      27, 264-266] and Mueller and Lloyd [(1948) Proceedings of the National Academy of
      Science, U.S.A., 34, 223-227], both of which used real objects or line
      stereograms. We tested stereopsis using both random-dot and line stereograms and,
      in agreement with these studies, found that stereopsis is indeed possible in dark
      adaptation. We also measured stereo acuity and positional acuity (both of which
      are examples of hyperacuity) and compared these with grating acuity at several
      levels of light and dark adaptation. At all illumination levels tested, acuities
      for stereopsis and relative line position were both higher than for grating
      acuity. As light levels decreased, positional and grating acuity declined in
      parallel fashion, whereas stereoacuity declined more steeply.

PMID- 8160395
TI  - Smooth pursuit eye movements with imaginary targets defined by extrafoveal cues.
AB  - Initiation of smooth pursuit eye movements was studied using imaginary targets
      defined by pairs of small spots ("cues") moving together in step-ramp motion. The
      arrangement of cues and imaginary target were either "two-sided"--cues far apart
      and imaginary target midway between, or "one-sided"--cues 4 deg apart and
      imaginary target to one side of the cue pair. (1) Pursuit of two-sided stimuli
      was much better than pursuit of one-sided stimuli and was often as good as
      pursuit of a real foveal target. (2) Experiments with various cue configurations
      suggest an attribute required for vigorous pursuit: "foveal enclosure".
      Configuration information is available to the pursuit system immediately after
      the onset of motion. (3) Pursuit of imaginary targets is markedly degraded by a
      background; the effect is strongest for a background at the fovea and weaker for
      an eccentric background, including one at the cue location.

PMID- 8160396
TI  - The effects of acetazolamide in albino rabbits, pigmented rabbits, and humans.
AB  - In three separate experiments albino rabbits, pigmented rabbits, and humans were
      tested following administration of acetazolamide and without acetazolamide. In
      all three experiments, we recorded electroretinograms (ERGs) under dark adapted
      and light adapted conditions and measured the b-wave amplitudes. Dark adapted ERG
      b-wave amplitudes were increased following administration of acetazolamide as
      compared to control conditions, in albino rabbits, pigmented rabbits and humans.
      Light adapted b-wave amplitudes showed no statistically significant changes as a
      function of acetazolamide administration although in all three experiments there
      was a trend toward light adapted b-wave amplitude reduction following
      administration of acetazolamide. In the human experiments, ERG a-wave amplitudes
      were also measured. Light adapted a-wave amplitudes were reduced following
      administration of acetazolamide. In the human experiments, several behavioral
      tests were performed, including L'Anthony desaturated D-15, Farnsworth-Munsell
      100 hue, Cogan-Gunkel chromatograph, Nagel anomaloscope, Goldmann-Weekers dark
      adaptometry. There were no consistent changes in the human dark adaptation
      thresholds or color discrimination, although several measures approached
      significance.

PMID- 8160397
TI  - Response univariance in bull-frog rods with two visual pigments.
AB  - Rods in the bull-frog retina contain varying proportions of rhodopsin (lambda max
      = 502 nm) and porphyropsin (lambda max = 527 nm) in a dorso-ventral gradient from
      the porphyropsin-rich dorsal rim to the virtually pure rhodopsin fields of the
      central and ventral retina. We investigated if quantal excitations in the same
      rod are different depending on whether they are initiated by isomerization of a
      rhodopsin or a porphyropsin molecule. Current photoresponses were recorded from
      dark-adapted rods by sucking the outer segment into a recording pipette. The
      relation between pigment composition and spectral sensitivity was established by
      comparison with microspectrophotometrically measured absorbance spectra of rods
      from the same neighbourhood. Rods with suitable porphyropsin: rhodopsin mixtures
      (ideally between 1:4 and 1:2) were stimulated with flashes of red (608 nm) and
      blue (465 nm) light, whereby the red light will isomerize porphyropsin much more
      often than rhodopsin, and the reverse will be true of the blue light. The
      amplitude and shape of the single-photon response were found to be identical for
      the "red" and "blue" flash series to within measurement error (ca 10%). This
      indicates that the quantal responses initiated by the two pigments are identical.

PMID- 8160398
TI  - Human brain responses to different image contrasts.
AB  - Human brain activity was evoked by a dynamic random-dot display in which a square
      wave grating appeared and disappeared at regular intervals. Grating visibility
      was determined by one of four different contrasts: texture, stereo disparity,
      luminance, or color. Scalp fields measured with 31 electrodes were used to
      estimate epicortical potential fields. The estimation procedure required detailed
      anatomical data for each subject. These were obtained from magnetic resonance
      images. A three-dimensional digitizer and a stereotactic headgear were used to
      accurately merge the frame of reference of the magnetic resonance image with that
      of the evoked potential. Epicortical potential fields provided a better indicator
      of where brain activity is evoked than did scalp fields. These procedures also
      corrected for anatomical variations between scalp and brain from subject to
      subject. In two right-handed female subjects, evoked activity was observed in the
      left posterior parietal and the right occipital, parieto-occipital and posterior
      temporal cortices. Evoked activity was observed in the left parietal cortex for
      luminance processing, in the right parietal cortex for texture processing and in
      the right temporal cortex for color processing, which was selective for the
      particular contrast.

PMID- 8160399
TI  - Spatial-frequency specific contrast gain and flicker masking of human transient
      VEP.
AB  - We studied the effects of grating contrast and luminance-flicker masking on the
      early waves of human visually evoked potentials (VEPs) recorded at the onset
      offset of sinusoidal gratings of varying spatial frequencies (SFs). At high SFs,
      the response waveform was simple and VEP was dominated by a negative wave (N110).
      At low SFs, several positive-negative deflections were recorded, the earliest
      dominating wave being positive (P90). The amplitude of P90 was saturated at a
      contrast of about 0.1 and it was attenuated by flicker masking. Masking involved
      to a lesser extent the waves following P90. It was weaker at the flicker
      frequency of 5 Hz than at 10 and 20 Hz. No flicker masking was found at SFs
      higher than 2-4 c/deg. At medium and high SFs, VEPs were obtained at higher
      contrast levels. No saturation (max contrast tested 0.5) and no flicker masking
      of N110 were observed. These results suggest that the early VEP components
      recorded at low and high SFs are related to different types of neuronal activity.
      Correlation between VEP properties and properties of magnocellular and
      parvocellular pathways is considered with an emphasis on recent morphological
      data about the human retina.

PMID- 8160400
TI  - A simple mechanism for emmetropization without cues from accommodation or colour.
AB  - We propose and test the simple hypothesis that a chicken eye can emmetropize
      without cues derived from accommodation or colour just by maximizing retinal
      image contrast. Using different translucent occluders with known modulation
      transfer functions we found that deprivation myopia is correlated with the amount
      of image degradation. Equipped with a long-term integrator, a mechanism
      minimizing image degradation by changing the axial eye growth rate would
      therefore be sufficient to place the plane of focus of the eye at the average
      viewing distance.

PMID- 8160401
TI  - Coherence thresholds for discrimination of motion direction in infants.
AB  - The sensitivity of 3-month-old infants to direction of motion in random-dot
      patterns was assessed by measuring coherence thresholds for the discrimination of
      a pattern, in which opposite directions were segregated into alternate horizontal
      strips, from an unsegregated pattern. The coherently moving dots had a
      displacement size of 0.16 deg (velocity 8 deg/sec), and their direction of motion
      reversed periodically. For both infants and an adult subject coherence thresholds
      decreased with increasing height of the segregated strips, and with increasing
      duration of the interval between direction reversals. However the infants
      required larger minimum heights and longer minimum durations in order to extract
      motion direction. Even under the best conditions infants were markedly less
      sensitive, with coherence thresholds of around 50%, compared with 5-7% for the
      adult. In addition, within the group of infants coherence thresholds were
      negatively correlated with age. This developmental increase in motion sensitivity
      at an intermediate velocity suggests that a large part of the improvement in
      upper and lower velocity thresholds during development is a result of a uniform
      increase in sensitivity across all velocities, though the results do not rule out
      additional specific improvements in sensitivity at the extremes of the velocity
      range.

PMID- 8160402
TI  - Efficient and unbiased modifications of the QUEST threshold method: theory,
      simulations, experimental evaluation and practical implementation.
AB  - QUEST [Watson and Pelli, Perception and Psychophysics, 13, 113-120 (1983)] is an
      efficient method of measuring thresholds which is based on three steps: (1)
      Specification of prior knowledge and assumptions, including an initial
      probability density function (p.d.f.) of threshold (i.e. relative probability of
      different thresholds in the population). (2) A method for choosing the stimulus
      intensity of any trial. (3) A method for choosing the final threshold estimate.
      QUEST introduced a Bayesian framework for combining prior knowledge with the
      results of previous trials to calculate a current p.d.f.; this is then used to
      implement Steps 2 and 3. While maintaining this Bayesian approach, this paper
      evaluates whether modifications of the QUEST method (particularly Step 2, but
      also Steps 1 and 3) can lead to greater precision and reduced bias. Four
      variations of the QUEST method (differing in Step 2) were evaluated by computer
      simulations. In addition to the standard method of setting the stimulus intensity
      to the mode of the current p.d.f. of threshold, the alternatives of using the
      mean and the median were evaluated. In the fourth variation--the Minimum Variance
      Method--the next stimulus intensity is chosen to minimize the expected variance
      at the end of the next trial. An exact enumeration technique with up to 20 trials
      was used for both yes-no and two-alternative forced-choice (2AFC) experiments. In
      all cases, using the mean (here called ZEST) provided better precision than using
      the median which in turn was better than using the mode. The Minimum Variance
      Method provided slightly better precision than ZEST. The usual threshold
      criterion--based on the "ideal sweat factor"--may not provide optimum precision;
      efficiency can generally be improved by optimizing the threshold criterion. We
      therefore recommend either using ZEST with the optimum threshold criterion or the
      more complex Minimum Variance Method. A distinction is made between "measurement
      bias", which is derived from the mean of repeated threshold estimates for a
      single real threshold, and "interpretation bias", which is derived from the mean
      of real thresholds yielding a single threshold estimate. If their assumptions are
      correct, the current methods have no interpretation bias, but they do have
      measurement bias. Interpretation bias caused by errors in the assumptions used by
      ZEST is evaluated. The precisions and merits of yes-no and 2AFC techniques are
      compared.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8160403
TI  - Some temporal aspects of stereoacuity.
AB  - Stereoacuity thresholds improve considerably with practice when measured using
      three vertical lines 15' apart horizontally and presented briefly. For
      experienced observers, these thresholds are relatively independent of exposure
      time for stimulus durations smaller than 100 msec. The thresholds are 2-3 times
      larger when the outer flanking lines are shown continuously than when they and
      the central target line are turned on and off simultaneously. When the target and
      flanking lines are shown sequentially, stereoacuity thresholds can be predicted
      from the number of times the configuration is presented. Changes in thresholds
      can be measured for intervals as small as 5 msec between successive presentation
      of the relative disparity configuration. The underlying mechanism is modeled well
      by a first order auto-regression process.

PMID- 8160404
TI  - The role of delineation and spatial frequency in the perception of the colours of
      the spectrum.
AB  - The observations of the spectrum made by Newton, Young, Wollaston and Helmholtz
      are approximated and accounted for. Increasing the number of delineations allows
      progressively more bands differing in colour to be perceived, in addition to the
      three blocks of colour seen in the undelineated spectrum. The rate at which
      further delineation permits more colours to be observed decreases, however, so
      that up to 30 colours can be perceived in the subdivided spectrum. The wavelength
      discrimination measurements agree well with previous data. Enhanced colour
      discrimination is shown to require luminance contrast transients containing only
      the first few Fourier harmonics.

PMID- 8160405
TI  - The spatial properties of binocular suppression zone.
AB  - Spatial properties of binocular suppression zones were studied with one
      dimensional difference of Gaussian (DOG) patterns. Two parallel DOG patterns were
      presented in one eye and a single DOG, perpendicular to the double DOG, was
      presented to the other eye. When viewed together, the probability of seeing the
      portion of the single DOG in between of the double DOG depended on the separation
      of the double DOG stimulus. Threshold separations for detecting an intermediate
      segment of the single DOG pattern (binocular suppression zones) were measured as
      a function of spatial frequency, contrast and orientation of the stimuli. The
      diameter of suppression zone decreased proportionally with increasing peak
      spatial frequency of the DOG patterns. The vertical dimension of the suppression
      zone was larger than the horizontal dimension at low spatial frequencies but the
      inverse tended to occur at high spatial frequencies. Diameter of the suppression
      zone increased rapidly with increasing contrast of the stimuli when the contrast
      was lower than 20-30% but asymptoted at higher contrasts.

PMID- 8160406
TI  - Relationship between spatial integration and spatial spread of contrast energy in
      detection.
AB  - Detection efficiencies were measured for two kinds of grating stimuli. The
      stimuli of the first kind were uniform square shaped cosine gratings of various
      sizes but of constant spatial frequency. The stimuli of the second kind were
      composed of nine small grating patches of the same spatial frequency arranged
      into a square array. The array size was varied by changing the inter-patch
      distance. The efficiencies for the two kinds of stimuli obeyed the same
      decreasing function of area defined by the respective outlines of the grating
      patch array and the uniform grating. The result means that detection efficiency
      is not determined by the retinal area stimulated, but by the distances between
      different parts of stimulus, i.e. the spatial spread of contrast energy, which
      can be described by a radial moment measure computed from the image.

PMID- 8160407
TI  - The scale bandwidth of visual search.
AB  - Observers were asked to locate a target in a brief, two-scale display. Accuracy
      of locating the target was measured as a function of the ratio between the two
      scales. At each scale ratio, the probability of locating the target as a function
      of the number of elements is well fit by the idea that the observer accurately
      monitors only a "critical" number of elements. The dependence of critical number
      on scale ratio is well accounted for by a model that assumes that the observer's
      decision is based on an evenly spaced array of samples. The sample spacing is
      under attentional control, but is always uniform.

PMID- 8160408
TI  - Dissociation of local and global processing in visual agnosia.
AB  - Subsequent to strokes in the right and left inferomedial occipito-temporal lobes,
      two patients became prosopagnosic and alexic, respectively. They also show a
      complementary dissociation of the analysis of handwritten text. The patient with
      the right posterior stroke can read it but not recognize whose handwriting it is;
      the patient with the left posterior stroke cannot read the text but knows who
      wrote it. The analysis of spatial vision revealed that the prosopagnosic patient
      has no problem with seeing texture elements when presented in isolation. Yet she
      performs poorly with Moire and texture perception, i.e. she suffers from a
      selective loss of global visual perception. The alexic patient performs well with
      Moire patterns but neither with (complex) texture elements nor with textures. She
      seemingly can locally and globally process patterns composed of simple figural
      elements but fails with stimuli that require the integration of features. This
      finding of a concomitant dissociation of local and global visual processes in the
      two patients supports the view that prosopagnosia as well as alexia are the most
      conspicuous aspects of more general alterations of visual perception.

PMID- 8160409
TI  - Disappearance of stationary visual phantoms under high luminant or equiluminant
      inducing gratings.
AB  - The visibility of stationary phantoms was measured by human observers in two
      experiments. The phantom visibility declined with the increase of the mean
      luminance of black/white inducing gratings, falling near to zero at a mean
      luminance high above 80 cd/m2. The phantoms also disappeared when the red/green
      inducing gratings were subjectively equiluminant. The implications of these
      results are discussed in relation to the grating induction effect and to the
      functional correlations with the magnocellular system's activity.

PMID- 8160410
TI  - Temporal integration at equiluminance and chromatic adaptation.
AB  - The present study showed that at equiluminance the critical duration of temporal
      integration became shorter as the chromatic saturation of an adaptation field was
      increased. These results suggest that the chromatic coding system (which is
      assumed to posses poorer temporal resolution or larger temporal integration time
      than the luminance coding system) can change its temporal integrating
      organization with its own adaptation level, independently of the luminance
      system.

PMID- 8160411
TI  - Mechanisms of chromatic rod vision in scotopic illumination.
AB  - After viewing a coloured patch for 30 sec, successive contrast colours were
      triggered by stimulating either rods or cones. The conditions were arranged so
      that the rod and cone stimuli matched both with respect to chromaticness and
      brightness in a chromatically neutral state of adaptation. The results showed
      that the contrast colours triggered by rods were strikingly similar to those
      triggered by cones. Yet, the scotopic contrast colours, as compared with the
      photopic ones, were generally found to be somewhat displaced toward blue. This
      displacement was attributed to the difference in test conditions. Thus, it was
      suggested that, although rods may excite all the different types of spectrally
      opponent cells, they generally tend to prefer the short-wave cells. Moreover, it
      was concluded that the scotopic successive contrast colours are triggered by rod
      signals feeding into the primary rod pathway and therefore must originate
      centrally to the receptor level.

PMID- 8160412
TI  - Directional anisotropy of motion sensitivity across the visual field.
AB  - There is an implicit assumption in most models of movement direction perception
      that sensitivity to motion is directionally isotropic, i.e. equal for movement in
      all directions. However, most previous research on directional effects on human
      motion perception have measured responses (e.g. manual reaction times) to
      suprathreshold stimuli rather than motion sensitivity. I investigated this
      possibility by measuring monocular sensitivity to motion coherence in small field
      random-dot kinematograms with global leftwards or rightwards motion as a function
      of eccentricity along the horizontal meridian in each eye of six observers.
      Although foveal motion sensitivity was isotropic, small but significant
      differences (about 0.1 log units) in sensitivity in favour of centripetal motion
      were observed at eccentricities between 5.0 and 12.5 deg. Motion anisotropy was
      significantly larger in the temporal than the nasal visual hemifield. In a second
      experiment, motion coherence thresholds for upwards and downwards movement were
      measured foveally and at +/- 5 deg on the vertical meridian. At the fovea, no
      difference in sensitivity to upwards vs downwards motion was observed but these
      vertical axis thresholds were significantly higher than foveal thresholds for
      movement along the horizontal axis. Directional anisotropy in favour of
      centripetal motion was present in the inferior visual field but directional
      isotropy was found for the superior visual field. Perhaps this generally
      heightened sensitivity to centripetal directions may function normally to
      facilitate figure/ground segmentation in the presence of centrifugally-moving
      background contours that typically accompany forward locomotion.

PMID- 8160413
TI  - Effects of background color on reaction time to stimuli varying in size and
      contrast: inferences about human M channels.
AB  - In two experiments we looked at the effects of the color of equiluminant
      backgrounds on simple reaction time (RT) to increment and decrement spot-stimuli
      varying in diameter. When comparing both red vs blue and red vs green
      backgrounds, we found that for the smallest diameter stimuli, RTs tended to be
      faster with red background; however, as the diameter of the stimuli increased,
      RTs were faster with the blue or green backgrounds. This trend held only for
      increment stimuli; no systematic or significant differences between RTs to
      decrement stimuli presented on red vs either blue or green backgrounds were
      found. We discuss these results in terms of the effects of diffuse lights of
      varying wavelength on magnocellular-channel activity.

PMID- 8160414
TI  - Stereo matching precedes dichoptic masking.
AB  - Stereo matching can intervene to prevent dichoptic masking. In a dichoptic
      masking paradigm we measured the contrast threshold for a bar target, presented
      to one eye, as a function of the contrast of an identical masking bar, presented
      at retinal correspondence in the other eye. Confirming previous studies of
      dichoptic masking with sinusoidal gratings, the test bar thresholds rose
      proportionally with increasing masking contrast. This threshold elevation was
      almost nullified when an extra bar was presented to the eye seeing the test
      stimulus. Release from masking occurred when the disparity between the masking
      bar and extra bar was < 20 min arc over a range of contrast levels (8-45%), and
      for bars containing either broad spatial frequency spectra or bars with only high
      spatial frequencies (peak = 12 c/deg). The latter result rules out an explanation
      for the release from masking based on contrast discrimination in low spatial
      frequency channels. The extra bar was effective in releasing the test bar from
      masking as long as the extra bar's contrast was greater than about one-fifth the
      contrast of the mask, a result that suggests that there is a contrast threshold
      for stereo matching. We interpret our findings to indicate that a stage of stereo
      matching occurs prior to the neural site limiting dichoptic contrast
      discrimination.

PMID- 8160415
TI  - Perceived contrast of gratings and plaids: non-linear summation across oriented
      filters.
AB  - Plaids composed of two orthogonal sine-wave gratings appeared to be of lower
      contrast than single gratings of the same Michelson luminance contrast. This
      effect for plaids was obtained at all spatial frequencies (1-16 c/deg) and
      contrast levels (2-32%). Contrast-matching data plotted as a function of the
      angle between plaid components (0-90 deg) and as a function of spatial frequency
      and standard contrast level were consistent with a model in which the response of
      each orientation-tuned spatial frequency channel is a threshold-corrected power
      function of contrast, and is followed by quadratic summation of responses across
      all channels. The best-fitting contrast-response exponent in the main experiment
      was 0.63. Analysis of several other data-sets suggested a slightly higher value,
      0.80. The same model gave a good account of contrast-matching between simple and
      compound (two-component) one dimensional gratings, accounting in particular for
      the apparent increase in contrast summation exponent at low contrasts reported by
      Quick, Hamerly and Reichert [(1976) Vision Research, 16, 351-355]. The model can,
      with one further assumption, account for the finding that contrast-matching
      between sine-wave and square-wave gratings depended only on the amplitude at the
      fundamental frequency. Comparison with contrast discrimination studies suggests
      that internal noise (variance of a channel's contrast-response) is not constant,
      but increases approximately in proportion to the mean response.

PMID- 8160416
TI  - Instability of ocular torsion during fixation: cyclovergence is more stable than
      cycloversion.
AB  - We investigated spontaneous variation of binocular torsion. Variation was
      expressed as SD of torsional eye positions measured over periods up to 32 sec.
      Subjects viewed a single dot target for periods of 32 sec. In half of the trials
      a large random-dot background pattern was superimposed on the dot. The movements
      of both eyes were measured with scleral induction coils. Spontaneous torsional
      movements were largely conjugate: cyclovergence was much more stable than
      cycloversion. This difference was not due to roll head movements. Stability of
      cyclovergence was improved by the background pattern. Although overall stability
      (SD of position) of cycloversion was unaffected by a background, the background
      induced or enhanced a small-amplitude torsional nystagmus in 3 out of 4 subjects.
      We hypothesize that the difference in stability of cycloversion vs cyclovergence
      reflects the greater importance of torsional retinal correspondence, compared to
      absolute torsional position. In two subjects we found evidence for the existence
      of cyclophoria, manifested by systematic shifts in cyclovergence caused by the
      appearance and disappearance of the background.

PMID- 8160417
TI  - Cortical dynamics of feature binding and reset: control of visual persistence.
AB  - An analysis of the reset of visual cortical circuits responsible for the binding
      or segmentation of visual features into coherent visual forms yields a model that
      explains properties of visual persistence. The reset mechanisms prevent massive
      smearing of visual percepts in response to rapidly moving images. The model
      simulates relationships among psychophysical data showing inverse relations of
      persistence to flash luminance and duration, greater persistence of illusory
      contours than real contours, a U-shaped temporal function for persistence of
      illusory contours, a reduction of persistence due to adaptation with a stimulus
      of like orientation, an increase of persistence with spatial separation of a
      masking stimulus. The model suggests that a combination of habituative, opponent,
      and endstopping mechanisms prevent smearing and limit persistence. Earlier work
      with the model has analyzed data about boundary formation, texture segregation,
      shape-from-shading, and figure-ground separation. Thus, several types of data
      support each model mechanism and new predictions are made.

PMID- 8160418
TI  - Lens accommodation evoked by microstimulation of the superior colliculus in the
      cat.
AB  - Accommodative responses to microstimulation of the superior colliculus (SC) of
      cats were investigated by measuring dioptric changes of the eye with a high-speed
      infrared optometer. Lens accommodation was elicited by low-current stimuli (< or
      = 20 microA) of the rostral portion of the SC, which corresponds to the
      representation of the central visual field. The low-threshold area for evoking
      lens accommodation was distributed from the superficial to intermediate layers of
      the SC. The latency of accommodative responses was 198.3 +/- 34.6 msec (mean and
      SD). The duration of accommodation was highly correlated with the duration of
      stimulation. These findings suggest that the SC plays an important role in the
      control of lens accommodation.

PMID- 8160419
TI  - Changes in the light-sensitive current of salamander rods upon manipulation of
      putative pH-regulating mechanisms in the inner and outer segment.
AB  - The light-sensitive current of dark-adapted rods isolated from the Ambystoma
      retina was recorded while either the inner or the outer segment (IS or OS)
      protruding from the suction pipette was exposed to treatments intended to reveal
      the physiological roles of pH-regulating transport mechanisms. Applied to the IS,
      both amiloride (presumed to block Na+/H+ exchange, 2 mM) and 4-4'
      diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) (presumed to block
      bicarbonate transport, 0.1 mM) generally abolished light sensitivity completely
      but reversibly, consistent with acidification of the IS. Yet, the circulating
      ("dark") current often persisted, implying that the OS was not acidified. Applied
      to the OS, amiloride depressed but DIDS increased the dark current and
      photoresponses. Given the fact that the current increases with rising OS-pHi,
      this suggests alkalinization, which could be due to DIDS inhibiting bicarbonate
      extrusion by HCO3-/Cl- exchangers in the OS. Consistent with this idea, replacing
      external Cl- by other anions increased the current as would be expected if HCO3
      /Cl- exchange is reversed. We propose that the IS and OS manage their acid
      balances independently and with different sets of transport mechanisms. Acidosis
      in either compartment suppresses the photosensitivity of the rod, but by
      differing mechanisms.

PMID- 8160420
TI  - [Quantitative analysis of the phospholipid composition of the myocardium in
      experimental diabetes mellitus: effect of total ischemia].
AB  - Phospholipid composition was studied in the myocardium of rats and rabbits with
      alloxan diabetes developed after intravenous of intraperitoneal administration of
      alloxan and complicated by 60-min total ischemia. The diabetes developed within 4
      weeks thereafter heart tissue was isolated and used for biochemical analyses.
      Total cardioplegic ischemia was simulated in the perfused heart after drastic
      interruption of perfusion. Composition of myocardial phospholipids was altered in
      alloxan diabetes: content of lysophosphoglycerides, lysophosphatidylcholine,
      lysophosphatidylethanolamine and of sphingomyelin was increased, while
      cardiolipin and phosphatidylethanolamine were decreased. In the diabetes-impaired
      heart tissue, a 2-fold increase was detected in the ratio of
      cholesterol/phospholipids, which corresponded to the viscosity of plasma
      membranes. Total ischemia within 60 min caused a further increase in the levels
      of lysophosphoglycerides in the diabetes-impaired tissue. Considerable
      differences in the content of phospholipids were maintained in control and
      diabetes-impaired heart tissues after ischemia and reperfusion; these differences
      were observed in the preischemic group. Thus, phospholipid composition was
      altered in the diabetes-impaired myocardia in presence and/or absence of
      ischemia.

PMID- 8160421
TI  - [Antioxidant vitamins and age-related retinal dystrophy].
AB  - Importance of free radical oxidation in development of age-dependent dystrophy of
      retina was studied. The newly developed hypothesis of the disease pathogenesis
      suggests that an increase in the rate of photosensitized free radical oxidation
      occurred in retina tissue due to a deficiency in reduction equivalents in these
      patients as well as to a lack of exogenous antioxidants. Complexes of vitamins
      antioxidants were advanced for treatment of the patients with sclerotic
      maculodystrophy.

PMID- 8160422
TI  - [Characteristics of the humoral immune system and lipid peroxidation processes in
      people living in territories contaminated with radionuclides].
AB  - Among 33 patients with Stage II hypertension, 25 persons were inhabitants of the
      Russian radionuclide-contaminated areas and 8 patients had no prior contacts with
      ionizing radiation (control). All the patients examined were maintained within 4
      weeks on a diet, radioprotective effect of which was realized due to the elevated
      content of sulfur containing amino acids, antioxidants and complexes. In the
      patients who lived in the radionuclide-contaminated areas, a moderate activation
      of lipid peroxidation was detected simultaneously with marked alterations in the
      humoral component of the immunity system, which involved a considerable increase
      in the levels of IgG and complements C3 and C4. A decrease in content of malonic
      dialdehyde and diene conjugates as well as normalization of IgG and decrease in
      content of IgA, IgM and C3 were observed in blood plasma of the patients on diet.
      Supplementation of omega 3 polyunsaturated fatty acids (omega 3-PUFA), 5 g/day
      and alpha-tocopherol, 12.5 mg/day, to the diet elevated the serum concentrations
      of all lg classes, which suggests the presence of an immunomodulating effect of
      omega 3-PUFA. Moreover, the content of malonic dialdehyde was not increased in
      blood plasma if 3-PUFA was used. Hence, increased alpha-tocopherol levels should
      be used in the treatment of these patients with omega 3-PUFA (up to 5-7 mg per g
      PUFA) in order to stabilize lipid peroxidation.

PMID- 8160423
TI  - [Effect of polyunsaturated phosphatidylcholine on the activity of antioxidant and
      lipolytic enzymes in alimentary hypercholesterolemia in irradiated rats].
AB  - A high-cholesterol diet containing 3.5% cholesterol, 0.2% methyl thiouracil and
      20% of heated sunflower-seed oil caused an increase in the content of
      cholesterol, triacylglycerols, diene conjugates and in the activity of
      phospholipase A2 in rat liver and of serum total cholesterol and cholesterol of
      low density lipoproteins, and a decrease in the activity of hepatic cholesterol
      esterase, in the fractional activity of lecithin:cholesterol acetyl transferase
      (LCAT), in the activity of the enzymes involved in the lipolytic transformation
      of lipoproteins and in the serum levels of very low density lipoprotein
      cholesterol. The content of malonic dialdehyde in liver tissue and molar activity
      of LCAT in blood serum were increased after preirradiation (0.5 and 5.0 Gy) of
      rats kept on the cholesterol diet. The preparation of polyunsaturated
      phosphatidylcholine was shown to decrease the content of triacylglycerols and
      diene conjugates in liver tissue of rats with alimentary hypercholesterolemia. In
      rats irradiated in a dose of 0.5 Gy the phosphatidylcholine preparation decreased
      the content of cholesterol in liver tissue and blood serum, exhibited the
      normalizing effect on the content of cholesterol of high density lipoproteins, on
      the activity of superoxide dismutase and glutathione peroxidase; in a dose of 5.0
      Gy this phosphatidylcholine preparation normalized the content of malonic
      dialdehyde, activity of the enzymes involved in lipolytic transformation of
      lipoproteins and increased the LCAT activity.

PMID- 8160424
TI  - [Phospholipase A2 in the biochemical mechanisms of spleen lymphocyte reaction to
      x-ray irradiation of animals].
AB  - Preincubation of rat splenic lymphocytes with nonspecific mitogens and calcium
      ionophore A23187 led to the activity of phospholipase A2 which hydrolyzed
      arachidonoyl phospholipids and to increased cellular levels of free arachidonic
      acid. The effect of some substances was decreased as follows: A23187 > >
      lipopolysaccharide > phytohemagglutinin > concanavalin A. Dose-dependent
      activation of phospholipid hydrolysis and arachidonic acid release were observed
      within 6-12 hrs after X-ray irradiation of animals in doses of 0.5 and 1.0 Gy.
      The involvement of phospholipase A2 in deterioration of receptor interactions
      occurring during transmission of an activation signal in splenic lymphocytes in
      the early postirradiation period is discussed.

PMID- 8160425
TI  - [Effect of low-energy laser radiation on lipid peroxidation intensity].
AB  - Local effect of low-energy laser radiation was shown to alter the rate of lipid
      peroxidation in rat liver tissue which was manifested as a weak accumulation of
      primary and secondary lipid peroxidation products. The laser radiation effect
      proved to be generalized as the content of lipid peroxidation products was
      similarly altered both in liver tissue and in blood regardless of the radiation
      site.

PMID- 8160426
TI  - [Antioxidant activity of blood serum and blood enzymes in meningococcal
      infections in children and adults].
AB  - Aspartate transaminase activity (AST) was measured in the serum of children and
      adults suffering from generalized meningococcal infection. Activation of AST is
      only rarely detected in children, which is associated with higher protection from
      lipid peroxidation. The ratio between antioxidants and prooxidants was higher in
      children than in adults.

PMID- 8160427
TI  - [The effect of starvation of lipid peroxidation in synaptosomal and mitochondrial
      factions of various brain structures].
AB  - Content of lipid hydroperoxides (LHP) and malonic dialdehyde (MDA) was measured
      in homogenates of rat brain cortex (limbic, sensomotor and orbital cortex) and
      subcortex brain structures (hypothalamus, medulla oblongata, and midbrain) and in
      their synaptosomal and mitochondrial fractions within various periods of
      starvation 1, 2, 3, 5 and 7 days. Lipid peroxidation was shown to intensify
      distinctly in the brain regions studied especially in the sensomotor cortex only
      after relatively long-term starvation during 5-7 days. The rate of lipid
      peroxidation was considerably higher in mitochondrial fractions of these brain
      structures studied than in the synaptosomes; high contents of LHP and MDA was
      found in mitochondria. Activation of lipid peroxidation appears to be distinctly
      responsible for impairment of the structure and functional components of nervous
      cells occurring during long-term starvation.

PMID- 8160428
TI  - [Effect of chitosan sulfates on lipoprotein lipase activity].
AB  - Effect of commercially available preparations of chitosan sulfate on the total
      lipolytic activity was studied in rabbit blood. Chitosan sulfates, administered
      per os or intravenously, proved to be highly effective activators of lipolytic
      enzymes. The most distinct efficiency exhibited preparations with molecular mass
      of 60-120 x 10(3) and the rate of sulfation 1.20-1.35. After administration of
      the chitosan sulfates into hyperlipidemic rats a decrease in blood plasma VLDL
      and increased HDL content were observed.

PMID- 8160429
TI  - [The local humoral immune system in patients with malabsorption syndrome].
AB  - Content of IgA, IgG, IgM, C3 and C4 components of complement, properdin factor B,
      acid glycoprotein, alpha 1-antitrypsin, transferrin and ceruloplasmin were
      studied using immunochemical procedures in blood serum, gastric and duodenal
      contents of healthy persons and of patients after stomach resection. In patients
      with symptoms of malabsorption concentration of IgA and IgG was drastically
      increased in gastric and duodenal contents by 51% and 188%, respectively, and by
      53% and 371%, respectively. Local activation of the complement system was also
      observed, which involved an increase of C3 component in stomach and small
      intestine by 122% and 31%, respectively. As a result of postoperative
      anastomositis content of albumin and the properdin factor B was distinctly
      increased in the duodenum. The data obtained suggest that studies of various
      functional proteins in gastric and duodenal contents are recommended for
      evaluation of a disease genesis as well as for diagnosis of acute local
      inflammation.

PMID- 8160430
TI  - [B group vitamin metabolism in duodenal ulcer disease, hypertension, and ischemic
      heart disease].
AB  - No differences were found in the rate of metabolism of vitamins B1, B2, B6 and
      niacin either in healthy persons or in patients with duodenal ulcer, hypertension
      of the 2nd degree and with ischemic heart disease as shown by excretion of
      riboflavin, 4-pyridoxylic acid, 1-methyl nicotinamide and thiamin with urine
      which correlated with concentration of these vitamins and their coenzyme forms in
      blood plasma and erythrocytes. Dependence of these vitamins excretion with urine
      on their concentration in blood and the vitamins content in food appear to
      demonstrate similar consumption of vitamins B in the persons studied; at the same
      time, evaluation of the vitamins consumption in the patients with these forms of
      pathology should be performed using the criteria suitable for healthy persons.
      Dissimilar rates of metabolism of these vitamins described in literature might be
      related to differences in nutrition as well as to the use of nonspecific
      techniques for estimation of the vitamins. Besides, initial consumption of
      vitamin B2 was not sometimes considered, but deficiency in riboflavin caused
      considerable impairments of vitamin B6 and niacin metabolism.

PMID- 8160431
TI  - [Vitamin status of children with diabetes mellitus].
AB  - A vitamin status was studied in 32 children of both sexes at the age of 9-15
      years with insulin-dependent diabetes mellitus within 2-3 years. The adequate
      consumption of all the vitamins studied was found only in two children.
      Polyhypovitaminosis was detected in 19% of these children. Deterioration of
      riboflavin metabolism observed was manifest, as a decrease in the vitamin content
      in tissues in line with an increase in its excretion with urine. As a result of
      this impairment metabolism of vitamins B6 and PP was disturbed with development
      of these vitamins secondary deficiency of the non-alimentary type. Obligatory
      correction of the water soluble vitamin deficiency in the patients with diabetes
      mellitus is discussed.

PMID- 8160432
TI  - [Phospholipid composition of the liver mitochondrial membrane in thermal stress].
AB  - Content of phospholipids as well as activity of phospholipase A2 and
      lysophospholipase A1 were studied in the hepatic mitochondrial membranes of rats
      exposed to high temperatures. A decrease in the content of phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylinositol and increase in fractions of
      cardiolipin, phosphatidylserine, phosphatidic acid and lysophospholipids were
      detected in liver tissue mitochondria after heat stress. Alterations of
      phospholipid levels in the mitochondrial membranes correlated with the rate (36
      37 degrees and 41-43 degrees) and duration (2 and 4 hrs) of heat exposure. Under
      mild conditions of heat exposure, phospholipase A2 and lysophospholipase A1 were
      activated in rat liver mitochondrial membranes. With elongation of the heat
      effect up to 4 hr activation of the lipolytic enzymes was increased. Under most
      severe conditions of heat stress, a marked activation of phospholipase A2 was
      observed, while the activity of lysophospholipase A1 was decreased and approached
      to control values.

PMID- 8160433
TI  - [Preparation of physiologically active polymethylmethacrylate on lanthanoid
      silylamides].
AB  - Catalytic activity of silylamide derivatives of three-valent lanthanoids
      [(Me3Si)2N]3Ln (where Me-CH3; Ln-Pr, Sm, Eu, Gd, Tb, Er, Yb) was studied under
      conditions of low temperature polymerization of methacrylate. The reaction
      involved an anion-dependent mechanism and was accompanied by formation of block
      polymer. The physiological activity of the polymethacrylate produced was
      manifested as stimulation of the growth rate in bone tissue after its
      impairments. The organo-element fragment introduced into the polymer was
      responsible for this kind of activity.

PMID- 8160434
TI  - [Lipid peroxidation in blood plasma of experimental animals treated with
      naphthalene oil].
AB  - 40 rabbits were used in the experiments, where 10 animals were in control group,
      and 3 groups of the animals were treated with naphthalene oil obtained from
      various pit-holes NN 39, 54 and 88. The treatment course included 10 applications
      of naphthalene oil, which was placed on lateral body surface, 10 x 10 cm, a dose
      of 1.0 ml/kg, within 10 min. A state of lipid peroxidation was evaluated by
      measurement of hydroperoxides, diene conjugates and malonic dialdehyde in rabbit
      blood. Some decrease in content of lipoperoxides was observed in rabbits after
      the course of naphthalene oil treatment and the oil from the pit-hole 54
      exhibited the highest effect. These results may be involved in evaluation of the
      naphthalene oil medicinal effects as well as in working out recommendations to
      use the naphthalene oil not from usual reservoir, but namely from pit-hole 54 for
      treatment of patients with impaired lipid metabolism.

PMID- 8160435
TI  - [A method of determining catalase and superoxide dismutase in erythrocytes using
      an open-type analyzer].
AB  - Human erythrocyte catalase activity was studied involving the peroxidase reaction
      with ethanol and the reverse alcohol dehydrogenase reaction. The adequate kinetic
      parameters of the reaction were obtained under mild conditions of hemolysate
      preparation. Estimation of catalase activity in series of hemolysates enabled us
      to measure the activity values near 220.0 kU/ml of erythrocytes which
      corresponded to those in literature. Adaptation of the superoxide dismutase
      activity evaluation in erythrocytes was carried out using the basic system NADH
      phenazine methasulfate-tetrazolium blue and the analyzer FP-901 equipped for nine
      simultaneous measurements. The rate of base reactions was plotted and the linear
      correlation was found between the reaction inhibition per cent and content of
      erythrocyte hemolysate and of commercially available preparation of superoxide
      dismutase. The procedures are simple and reproducible and may be used in routine
      studies of antioxidants.

PMID- 8160436
TI  - [Optimization of determining human erythrocyte glutathione reductase activity
      using a semiautomatic analyzer].
AB  - A relatively simple procedure was developed for estimation of the glutathione
      reductase activity using half-automatic analyzer. The procedure involved:
      preparation of hemolysates with minimal rate of erythrocyte destruction;
      substitution of buffers with high ionic strength for 0.05 M Tris-HCl buffer not
      containing EDTA. Most effective period of preincubation was found; dependence of
      the reaction rate on FAD was studied. The procedure developed was approved using
      two types of half-automatic analyzer and the model FP-901 was shown to be the
      most suitable for estimation of the glutathione reductase holoenzyme activity.

PMID- 8160437
TI  - [The mechanism of amphetamine action of the neuromediator system of the brain].
AB  - Some biochemical patterns of the neurotransmitter system activity were studied in
      mitochondrial fraction of rat brain locomotor cortex and caudate nucleus under
      normal conditions as well as after short-term (60 min) and long-term (3 weeks)
      administration of amphetamine at a dose of 2.5 mg/kg. Under these conditions some
      alterations were detected in activity of monoamine oxidases of the A and B types
      involved in utilization of neurotransmitters as well as in content of
      catecholamines (dopamine, noradrenaline and serotonin). Similar alterations were
      also observed in the ratio between content of biogenic amines and their metabolic
      end-products: homovanillic and 5-hydroxyindole acetic acids which indicates the
      rate of the neurotransmitter metabolism. These alterations in parameters of the
      neurotransmitter systems were strongly individual and dissimilar depending both
      on localization in brain structures and on the step of the pharmacological
      treatment. Amphetamine appears to cause definite reciprocal alterations of the
      patterns studied: activation of the catecholamine-dependent mediation and
      inhibition of the serotoninergic reactions.

PMID- 8160438
TI  - [Modulation of the glucocorticoid receptor interaction with sodium ethazole].
AB  - The effect of sodium sulfaethidole on Types II and III glucocorticoid receptors
      was studied in liver cytosol fraction obtained from female Wistar rats of 180-200
      g body weight. Functions of Type II glucocorticoid receptors in liver cytosol
      were evaluated by triamcinolone 3H-acetonide and Type III glucocorticoid
      receptors by 3H-corticosterone. The Scatchard and Laynuiver-Berck analyses
      indicated that sodium sulfaethidole decreased the density of Type II
      glucocorticoid receptors and the complex association constant. A decrease in
      functions of Type II glucocorticoid receptors in the presence of the drug
      occurred by the competitive type. At the same time, sodium sulfaethidole
      increased greatly the function of Type III glucocorticoid receptors and an
      increase in the density of these receptors was realized noncompetitively. The
      decrease in the functions of Type II glucocorticoid receptors and increase in
      that of Type III receptors in the presence of sodium sulfaethidole suggest that
      the drug exhibits antiglucocorticoid properties.

PMID- 8160439
TI  - [The genomic variability of adenovirus serotype 7].
AB  - Genetic heterogeneity and evolutionary relationships among selected strains of
      adenovirus type 7 (Ad7) isolated in the former USSR were examined using the
      restriction endonuclease Cfr131 with a 4-base recognition cleavage site. The
      population of adenovirus type 7 showed less expressed genome polymorphism and
      significant structural distinctions as compared with that of adenovirus type 3.
      The Ad7 evolution in the USSR (1976-1988) independent on that demonstrated in
      other countries is discussed.

PMID- 8160440
TI  - [The immunity indices of animals immunized with the inactivated Marburg virus
      after infection with homologous virus].
AB  - The data on changes in the parameters of specific and nonspecific immunity after
      challenge of the immunized animals with Marburg virus are presented. Mediators of
      the immune response: tumor necrosis factor, interferon, were shown to play
      different roles in the development of the disease and "protection" of animals.
      The survival rate of the immunized animals after the challenge with Marburg virus
      was determined by the intensity and level of the immune response after challenge
      rather than by the levels of postvaccination immunity at the time of the
      challenge.

PMID- 8160441
TI  - [Experimental lyssavirus infection in chiropters].
AB  - Insectivorous bats, Pipistrellus pipistrellus in the active stage and hibernation
      were inoculated with bat unclassified Lyssavirus Aravan and Lyssavirus serotypes
      1 and 4. The influence of hibernation on the duration of the incubation period
      and the distribution of viruses in extraneural tissues was demonstrated. Clinical
      symptoms of the diseases caused by different strains are described.

PMID- 8160442
TI  - [Human and simian coronaviruses].

PMID- 8160443
TI  - [The experimental efficacy of vaccination with a recombinant yeast vaccine
      against hepatitis B in combination with immunomodulators].
AB  - Experiments in BALB/c mice were carried out to study a number of immunomodulators
      in combination with vaccination using a recombinant yeast hepatitis B vaccine.
      The use of poludan, ridostine, amixine, larifan, myekonide significantly enhanced
      specific antibody production and at least doubled cell-mediated immune response
      by 14 and 28 days postvaccination. The above-mentioned immunomodulators are
      planned to be used in vaccination with the recombinant yeast vaccine against
      hepatitis B.

PMID- 8160444
TI  - [An intranasal method of revaccination against mumps].
AB  - The effectiveness of revaccination against mumps was studied using different
      routes for administration of a live mumps vaccine from L-3 strain. Poor
      reactogenicity of the vaccine was observed after intranasal administration. The
      highest rise in titres of virus-neutralizing antibody was demonstrated in
      volunteers given the vaccine by the intranasal route. Revaccination of adults by
      both intranasal and subcutaneous routes induced production of antigen-specific
      memory cells. The results of the study attest to the usefulness of the intranasal
      route of vaccine administration in revaccinations against epidemic parotitis.

PMID- 8160445
TI  - [The immunogenic properties and prophylactic efficacy of a live polyvalent
      influenza vaccine in children 5 to 14 years old].
AB  - Production lots of a live influenza vaccine made of strains A/47/T (N1H1),
      A/47/6/2 (H3N2), and B/60/32 were used for vaccination of 3663 children aged from
      5 to 14 years inoculated twice with monovaccines, a trivaccine made of the above
      strains, or placebo. Both mono- and polyvaccine were practically areactogenic. An
      average per cent of subjects with a significant rise in antibody titres to the
      respective three antigens was 60%. The efficacy of the vaccination was 31.0-42.8%
      for monopreparations and 36.3% for the trivaccine. The studies showed the
      possibility and expedience of using for children the live influenza vaccine in
      the form of a polyvalent preparation including current influenza type A and B
      viruses.

PMID- 8160446
TI  - [An analysis of the amino acid sequence of the heavy subunit of the hemagglutinin
      in influenza virus A/Alma-Ata/1417/84].
AB  - An analysis of the amino acid sequence of influenza A/Alma-Ata/1417/84 (H1N1
      Hsw1N1 serovariant) virus hemagglutinin heavy chain deduced from the nucleotide
      sequence of cloned full-size DNA complementary to the 4th segment of genome RNA
      was carried out. Unlike A/New Jersey/8/76 virus, the hemagglutinin of the virus
      under study was found to be more similar in the rate of HA1 homology, amino acid
      sequence of the signal peptide, antigenic sites Sa, Ca, and the receptor-binding
      site to human influenza viruses isolated in the 1930-1980-ies, in particular to
      influenza A/Taiwan/1/86 virus. It is assumed that an influenza virus more adapted
      to the human population like the strain A/Alma-Ata/1417/84 may be an etiological
      factor of a new influenza pandemic.

PMID- 8160447
TI  - [The isolation and expression in E. coli of a recombinant plasmid containing the
      3'-terminal fragment of the cDNA of the influenza A virus nucleoprotein gene].
AB  - A recombinant plasmid pN62 determining the synthesis of a hybrid protein
      consisting of a full-size beta-galactosidase and C-terminus fragment of influenza
      A virus nucleoprotein was constructed. The complete identity of pN62 insert with
      the 3'-terminus cDNA fragment of influenza A virus NP-gene and conservation of
      beta-galactosidase reading frame was confirmed by Maxam-Gilbert sequencing of
      pN62. An expression of pN62 plasmid in E. coli JM103 in the presence of IPTG
      resulted in accumulation of fused protein as poorly soluble inclusion bodies in
      the bacterial cells. Analysis of E. coli JM103/pN62 bacteria lysates by 7% PAGE
      revealed that molecular weight of hybrid polypeptide was 18 kDa heavier than
      normal beta-galactosidase and corresponded to the previously deduced weight of
      135 kDa.

PMID- 8160448
TI  - [The main results of the research performed on AIDS under the Russian Government
      Scientific and Technical Program on National Priorities in Medicine and Public
      Health for 1992. The Expert Commission on AIDS of the Russian Government
      Scientific and Technical Program on National Priorities in Medicine and Public
      Health].

PMID- 8160449
TI  - [The brief performance results of scientific projects concluded in 1992 and
      financed under the Russian Government Scientific and Technical Program on
      National Priorities in Medicine and Public Health (research on viral
      infections)].

PMID- 8160450
TI  - [The register of scientific topics approved by the Expert Commission on AIDS of
      the Russian Government Scientific and Technical Program on National Priorities in
      Medicine and Public Health in 1993].

PMID- 8160451
TI  - [The antiviral action of recombinant receptorotoxins based on the diphtheria
      toxin and the human T-lymphocyte CD4-receptor].
AB  - A number of vectors expressing in E. coli hybrid proteins (receptorotoxins)
      composed of diphtheria toxin lacking the C-terminal region and CD4-receptor
      fragment including N-terminal region of the natural protein have been
      constructed. The receptorotoxins consisting of the CD4 fragment in their N
      terminal region were more stable. These recombinant receptorotoxins were cultured
      with HIV-infected Hut-78 cells and were shown to block HIV infection in vitro.

PMID- 8160452
TI  - Facts concerning the human immunodeficiency virus (HIV) infection and also the
      acquired immune deficiency syndrome (AIDS)

PMID- 8160453
TI  - Jamaican neuropathy revisited.

PMID- 8160454
TI  - Detection of oncogenic HPV DNA by a consensus polymerase chain reaction method in
      genital carcinomas in twenty women in Barbados.
AB  - Paraffinized tissue from Barbadian women with histologically proven genital
      carcinoma was subjected to a consensus polymerase chain reaction method. Nineteen
      patients had cervical and one, vaginal carcinoma. The histological types were 17
      squamous cell carcinoma, 2 adenocarcinoma and 1 adenosquamous carcinoma. HPV DNA
      was detected in 18/20 (90%). HPV DNA type 16 in 13 (65%), type 33 and type 45 in
      1 (5%) each and 3 (15%) could not be typed. HPV DNA, type 16, was detected in one
      (50%) of the two cases of adenocarcinoma and 12/17 (71%) cases of squamous cell
      carcinoma. DNA HPV, type 33, and type 45 were each detected in 1/17 (6%) cases of
      squamous cell carcinoma. No HPV DNA, type 18, was detected.

PMID- 8160455
TI  - Risk factors and treatment of endometrial carcinoma.
AB  - A twelve-year retrospective study of 54 consecutive cases of endometrial
      carcinoma revealed that post-menopausal bleeding was the commonest symptom, and
      the major associated risk factors were obesity and hypertension. Panhysterectomy
      was the corner-stone of treatment while adjunctive therapy was based on certain
      prognostic factors and the operator's preference.

PMID- 8160456
TI  - Cold-knife cervical conization.
AB  - Forty-six cervical conizations were performed over a ten-year period for
      diagnostic or therapeutic purposes. Twenty-nine women were under 45 years of age.
      The most common reason for conization was an abnormal Papanicolaou smear. The
      overall incidence of neoplasia was 80.4 per cent. The high complication rate of
      28.4 per cent emphasizes the need for a less traumatic technique of excisional
      biopsy.

PMID- 8160457
TI  - Occipital osteodiastasis in Jamaica.
AB  - The Jamaican Perinatal Morbidity and Mortality Survey (1986-1987) revealed nine
      cases of a previously unreported form of birth-related injury in the English
      speaking Caribbean--occipital osteodiastasis. Aspects of the clinical and
      pathological features of this form of occipital bone injury are presented and
      discussed. Our findings suggest that this lesion might occur more often than is
      currently accepted.

PMID- 8160458
TI  - The pattern of in-patient psychiatric referrals in a general hospital.
AB  - All patients referred for a psychiatric consultation from the adult wards of a
      General Hospital over a 10-month period were examined. The referral rate was
      1.4%. Twice as many female patients were referred as male patients. Parasuicide
      accounted for 68% of referrals. The most common psychiatric diagnoses were
      adjustment reaction (41%), depression (23%), alcohol dependence (5%) and
      schizophrenia (5%). In 30% of referrals, no psychiatric treatment was necessary;
      26% were transferred to the psychiatric unit and 17% were discharged to the out
      patients' psychiatric clinic. Explanations are offered for the "hidden"
      psychiatric morbidity in General Hospitals and the high percentage of referrals
      who did not need psychiatric follow-up. Suggestions are made for a better liaison
      between physicians and psychiatrists.

PMID- 8160459
TI  - Women's health beliefs regarding hypertension.
AB  - Two hundred and forty female clients attending primary health care centers in
      Montego Bay and the Kingston Metropolitan Area were interviewed to obtain
      information about their beliefs with regard to hypertension. This study revealed
      that the variables-perceived susceptibility, perceived severity and 'cue to
      action'-identified in the Health Belief Model need to be strengthened if patient
      compliance and adoption of health-promoting behaviours are to be realized. This
      study also pointed out the pressing need for health care providers to enhance
      health promotion programmes relative to hypertension. These programmes should be
      aimed at increasing clients' knowledge base and self-care abilities in order to
      to help prevent and/or control this disorder.

PMID- 8160460
TI  - Acute purulent pericarditis in children caused by haemophilus influenzae.
AB  - Acute purulent pericarditis caused by Haemophilus influenzae is an unusual
      condition, especially in childhood. In most cases, respiratory symptoms are the
      presenting features, and children aged less than 4 years are most often affected.
      A high index of suspicion and aggressive microbiological and cardiological
      evaluation are often warranted to make an early diagnosis. We herein report two
      cases of pericarditis caused by H. influenzae in children aged less than two
      years. Pericardiocentesis was performed in each case. Early recognition, rapid
      diagnosis and aggressive medical and surgical therapy are paramount in the
      successful treatment of this condition.

PMID- 8160461
TI  - Chronic triangular fibrocartilage complex tears. A case report and review of the
      literature.
AB  - The treatment of a young man with chronic symptomatic gross subluxation of the
      distal radio-ulnar joint of the right wrist secondary to traumatic disruption of
      the triangular fibrocartilage complex (TFCC) is described. At operation, a strip
      of tensor fascia lata was used to stabilize the distal radio-ulnar joint.
      Complete relief of pain and restoration of normal function was obtained following
      surgery. The literature on TFCC disorders is also reviewed.

PMID- 8160462
TI  - Successful pregnancies in patients with antiphospholipid syndrome treated with
      low-dose aspirin.
AB  - Four patients with bad obstetrical histories and with positive lupus
      anticoagulant tests were treated with low-dose aspirin, prednisone or heparin.
      They had pre-term deliveries of live babies who all survived.

PMID- 8160463
TI  - Bone marrow transplantation beyond treatment of aplasia and neoplasia.
AB  - Marrow transplantation has proved to be an important modality in the treatment of
      aplastic anemia, acute leukemia, and some other malignant diseases of hemopoietic
      cells. Much less attention has been paid to the role of marrow transplantation in
      the treatment of stem cell disorders such as sickle cell disease, chronic
      granulomatous disease, or Gaucher's disease. Allogeneic transplantation is
      successful in these disorders, but carries a considerable risk to the recipient.
      Autologous transplantation becomes a reality when efficient gene transfer with
      sustained expression is developed. As methods are developed to harvest
      hemopoietic stem cells from the peripheral blood and to amplify these cells
      without causing them to differentiate, transplantation will become increasingly
      valuable in the treatment of stem cell disorders.

PMID- 8160464
TI  - An experience in Japanese academic medicine.
AB  - The Japanese health care system has been highly praised for its universal access,
      freedom of patient choice, maintenance of a private system, and creative funding.
      Japanese citizens enjoy general good health, low infant mortality, and long life
      expectancy. Nevertheless, aspects of Japanese medical education, both graduate
      and undergraduate, and the structure of academic departments differ from those
      seen in the United States. A sabbatical spent teaching general internal medicine
      in Japan provided the experience for this review of the Japanese system. I
      describe the structure and function of departments of medicine and observations
      made at daily clinical teaching exercises in hospitals throughout the country.

PMID- 8160465
TI  - The skin as an immune organ.
AB  - As a protective interface between internal organs and the environment, the skin
      encounters a host of toxins, pathogenic organisms, and physical stresses. To
      combat these attacks on the cutaneous microenvironment, the skin functions as
      more than a physical barrier: it is an active immune organ. Immune responses in
      the skin involve an armamentarium of immune-competent cells and soluble biologic
      response modifiers including cytokines. Traversed by a network of lymphatic and
      blood vessels, the dermis contains most of the lymphocytes in the skin, other
      migrant leukocytes, mast cells, and tissue macrophages. Although the epidermis
      has no direct access to the blood or lymphatic circulation, it is equipped with
      immune-competent cells: Langerhans cells, the macrophage-like antigen-presenting
      cells of the epidermis; keratinocytes, epithelial cells with immune properties;
      dendritic epidermal T lymphocytes, resident cells that may serve as a primitive T
      cell immune surveillance system; epidermotropic lymphocytes, migrants from
      vessels in the dermis; and melanocytes, epidermal pigment cells with immune
      properties. Although the components of the epidermis and dermis work in concert
      to execute immune responses in the skin, for purposes of this review, we focus on
      the cells and cytokines of the epidermal immunologic unit, the frontline of
      immune protection against environmental toxins and microbes.

PMID- 8160468
TI  - Imaging of pediatric testicular problems.

PMID- 8160467
TI  - Vasectomy and prostate cancer.

PMID- 8160469
TI  - Urologic laparoscopic procedures.

PMID- 8160466
TI  - Why are low-density lipoproteins atherogenic?
AB  - Low-density lipoproteins (LDLs) carry most of the cholesterol in human plasma,
      and high levels of LDL cholesterol clearly cause heart disease. In recent years,
      many scientists have focused on elucidating the pathophysiologic steps that lie
      between elevated levels of LDL in the plasma and atherosclerotic plaques in the
      arterial wall. A large number of scientific studies indicate that oxidation of
      LDL within the arterial wall may be an important early step in atherogenesis. The
      uptake of oxidized LDL by macrophages is a likely explanation for the formation
      of macrophage foam cells in early atherosclerotic lesions. In addition, oxidized
      LDL has many other potentially proatherogenic properties.

PMID- 8160470
TI  - Treating impotence.

PMID- 8160471
TI  - Complete androgen blockade for metastatic prostate cancer.

PMID- 8160472
TI  - Reactive arthritis induced by Clostridium difficile.

PMID- 8160473
TI  - Acquired hemophilia in a patient with myeloma.

PMID- 8160474
TI  - Factitious physical disorders.

PMID- 8160475
TI  - Cytokines, neuropeptides, and other factors in cutaneous immune responses.

PMID- 8160476
TI  - Low-density lipoprotein oxidation and the pathogenesis of atherosclerosis.

PMID- 8160477
TI  - California AIDS Drug Assistance Program expansion.

PMID- 8160478
TI  - Another wake-up call.

PMID- 8160479
TI  - Transurethral insertion of a vaginal contraceptive suppository into the urinary
      bladder.

PMID- 8160480
TI  - Use of devices for mobility by the elderly.
AB  - Our study examined the use of devices for mobility by the elderly. We looked at
      whether the device was prescribed, who prescribed it, and how it was obtained.
      Seventy elderly people, age 75 years or older, who were current users of canes,
      walkers, or wheelchairs were interviewed. Seventy-one percent of the devices had
      been prescribed. The prescribed devices were chosen 45% of the time by physical
      therapists, 32.5% by physicians, and 22.5% by nurses. An exceptionally high
      percentage of wheelchair users (93%) in the skilled care facility may reflect
      economics (wheelchair and standard walkers are provided free) and perceived
      socialization benefits. This study shows that many elderly begin using devices
      for mobility on their own (94.3%). Clinicians need to be alert to these non
      prescribed devices to assure their appropriateness and safe use.

PMID- 8160481
TI  - The Wisconsin Women's Cancer Control Program.

PMID- 8160483
TI  - Chicken soup.

PMID- 8160482
TI  - Teens and domestic violence.

PMID- 8160484
TI  - Support for generalist track in medical school.

PMID- 8160485
TI  - Medicine ruled by the whims of tyranny.

PMID- 8160486
TI  - The outcome status of chronic pain patients 4 years after multidisciplinary care.
AB  - Thirty-three patients previously treated for a variety of chronic pain syndromes
      (largely non-surgical back problems) were selected for study on the basis of 2
      years or greater post-discharge status. A patient profile was developed revealing
      an 86% successful return-to-work rate and minimal use of narcotics 4 years after
      discharge. In addition, there was relatively low use of either inpatient or
      outpatient medical services after treatment. These patient behaviors were
      specific goals of the pain management program in which these patients had
      participated. Interesting data were also collected on medication use after
      treatment and methods of pain control used most successfully. Selected outcome
      variables were also studied across specific diagnostic categories (surgical v non
      surgical back problems, amputee pain, reflex sympathetic dystrophy, and others)
      for this group. In general, rather compelling positive outcomes are shown for the
      long-term effects of multi-disciplinary pain management.

PMID- 8160487
TI  - [An analysis of form variability by the methods of "geometrical morphometry": the
      demonstration of its potentials exemplified by the gnathosoma of ticks (Acari:
      Ixodes) and by the molar of voles (Mammalia: Alticola)].
AB  - New applied computer programs GRF, TPSRW, TPSLINE realize an idea of geometrical
      morphometrics and make it possible to study shape variation. Some results of
      their application are considered. Gnathosoma shape transformations among age and
      sex phases in tick, Ixodes ricinus, and third upper molar shape transformations
      among subspecies of vole, Alticola argentatus, are study cases. In tick,
      gnathosoma shape changes most significantly in males than in females, and age
      variation in total has twice higher magnitude as compared with sex differences.
      In vole, the most variable part of the tooth is talon, in general its complexity
      increases from south to north of the species area. A possibility of "vector"
      representation of principally "scalar" individual variation of the tooth shape is
      shown.

PMID- 8160488
TI  - [The sociality syndrome. A comparative study of the behavior of gerbils].
AB  - To explain the evolution of sociality the authors propose the hypothesis that
      every social interaction is based on the contest. The synergetic nature of any
      interaction determines the permanent involving partners in the contests and leads
      to increasing social pressure within community. The contestants' interactions
      inhibit an activity in one of the partners. Two possible evolutionary strategies
      of adaptation to increasing social density are: 1) an increase in resistance to
      the activity inhibition; 2) a retaining in memory the results of inhibition, i.e.
      reducing of ability to restore inhibited activity. Three species of gerbils
      (Gerbillidae): Mongolian (Meriones unguiculatus), Libyan (M. libycus), and midday
      gerbil (M. meridianus) were compared. Being similar in their ecology and
      behavioural repertoire three species differ strongly in extent of sociality: the
      highest in Mongolian gerbil and the lowest in midday one. The duration of social
      acts in laboratory groups of gerbils as well as frequency of acts delaying
      conflicts under natural conditions were assumed to correlate with increase in
      resistance to social pressure. Both parameters were higher in mongolian and
      libyan gerbils. The data on dynamics, asymmetry, and stability of social
      relations indicates more stable retaining in memory the results of interactions
      in Mongolian and Libyan gerbils than in midday ones but the latter restore
      inhibited activity more quickly. In the laboratory groups where the available
      space is compressed the midday gerbils maintain population at a level not lower
      than Mongolian ones and much higher than M. libycus. Moreover aggression within
      the group of midday gerbils doesn't result in rapid population decrease as in
      other two species.